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File： 09　特集 (難病)　松尾俊彦.pdf

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File： Clinical Case Reports 2023NTM.pdf

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File： Clinical Case Reports 2023Acanthamoeba.pdf

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

File： matsuo-tanaka-2023 orbital myxoma.pdf

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File： matsuo-et-al-2023-lacrimal-gland-mantle-cell-lymphoma.pdf

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File： matsuo-et-al-2023-bilateral-optic-neuritis-and-hypophysitis.pdf

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File： Clinical Case Reports 2023 Matsuo ANCA.pdf

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

File： ijms-24-04411-v2 NK-4 review.pdf

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File： cataract surgery ijerph-19-15796.pdf

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File： Clinical Case Reports - 2022 - Matsuo - Temporal association of vitreous hemorrhage and hypertension after COVID‐19 mRNA.pdf

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

(1) Background: Japanese Kampo medicine has its origin in ancient Chinese medicine. In 742, a Tang Dynasty monk named Jianzhen (Ganjin) was invited by Japanese clerics to visit Japan and teach commandments in Buddhism. Because of the dangers of the voyage and also other obstacles, he took 11 years to reach Japan on the sixth voyage and he was blind when he arrived in Japan. He was the first person in China to go to Japan to establish the Buddhism commandments, and he was also the first person in Japan to directly teach traditional Chinese medicine. Until now, there have been few reports in English about the details of the Chinese herbal medicines he brought to Japan, including the types of herbal medicines, pharmacological activities, and formulations. In the review, we systematically and comprehensively summarized Jianzhen’s life from the standpoint of his medical and pharmaceutical knowledge and the types and pharmacological activities of Chinese herbal medicines and prescriptions that were brought to Japan by Jianzhen; (2) Methods: A review was made on the relevant literature written by Chinese, Japanese, and English languages regarding the medical and pharmacological knowledge of Jianzhen, the 36 Chinese herbal medicines brought to Japan by Jianzhen, and the pharmacological and therapeutic effects of these 36 herbal medicines, as well as their formulations; (3) Results: The review of the literature proved that Jianzhen’s prescriptions served as a basis for current herbal medicines (Kampo) in Japan. In the process of the literature search, we found a book entitled Jianshangren (Holy Priest Jianzhen)’s Secret Prescription, which recorded the complete prescription of the 36 traditional Chinese medicines Jianzhen brought to Japan; (4) Conclusions: Jianzhen is one of the ancestors of traditional Chinese medicine/Kampo medicine, and he brought traditional Chinese medicine and medical books to Japan for patients. He made important contributions to the development of traditional Chinese medicine in Japan.

File： compounds-02-00022.pdf

DOI： 10.3390/compounds2040022

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File： JCEH sarcoidosis and lymphoma2022.pdf

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Idiopathic superior oblique muscle palsy is a major type of paralytic, non-comitant strabismus and presents vertical and cyclo-torsional deviation of one eye against the other eye, with a large vertical fusion range and abnormal head posture such as head tilt. Genetic background is considered to play a role in its development, as patients with idiopathic superior oblique muscle palsy have varying degrees of muscle hypoplasia and, rarely, the complete absence of the muscle, that is, aplasia. In this study, whole genome sequencing was performed, and single nucleotide variations and short insertions/deletions (SNVs/InDels) were annotated in two patients each in three small families (six patients in total) with idiopathic superior oblique muscle palsy, in addition to three normal individuals in one family. At first, linkage analysis was carried out in the three families and SNVs/InDels in chromosomal loci with negative LOD scores were excluded. Next, SNVs/InDels shared by the six patients, but not by the three normal individuals, were chosen. SNVs/InDels were further narrowed down by choosing low-frequency (<1%) or non-registered SNVs/InDels in four databases for the Japanese population, and then by choosing SNVs/InDels with functional influence, leading to one candidate gene, SSTR5-AS1 in chromosome 16. The six patients were heterozygous for 13-nucleotide deletion in SSTR5-AS1, except for one homozygous patient, while the three normal individuals were wild type. Targeted polymerase chain reaction (PCR) and direct sequencing of PCR products confirmed the 13-nucleotide deletion in SSTR5-AS1. In the face of newly-registered SSTR5-AS1 13-nucleotide deletion at a higher frequency in a latest released database for the Japanese population, the skipping of low-frequency and non-registration sorting still resulted in only 13 candidate genes including SSTR5-AS1 as common variants. The skipping of linkage analysis also led to the same set of 13 candidate genes. Different testing strategies that consisted of linkage analysis and simple unintentional bioinformatics could reach candidate genes in three small families with idiopathic superior oblique muscle palsy.

File： SO palsy WGS final ijms-23-08626.pdf

DOI： 10.3390/ijms23158626

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File： JCEH2022 CAR-T.pdf

DOI： 10.3960/jslrt.22007.

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File： ijerph-19-08655.pdf

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

File： 医学のあゆみ 3光電変換色素薄膜型の人工網膜OUReP(オーレップ)松尾俊彦.pdf

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Language：Japanese  

File： モンゴル伝統医学とその現代的意義2022.pdf

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

File： life-12-00041.pdf

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

File： Mol Clin Oncol2021 proton beam.pdf

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

A 34-year-old Japanese person with male gender identity who had been taking intramuscular injection of methyltestosterone depot for 11 years after bilateral mastectomy noticed blurred vision 5 days after the second vaccination for COVID-19 (Tozinameran; Pfizer-BioNTech) in the interval of 3 weeks following the first vaccination. The patient was diagnosed as granulomatous iritis with mutton-fat keratic precipitates and small iris nodules at the pupillary margin in the right eye and began to have 0.1% betamethasone eye drops with good response. The patient, however, continued to have fever and malaise and showed a high level of serum soluble interleukin-2 receptor (sIL-2R) even 4 weeks after the second vaccination. Computed tomographic scan disclosed mediastinal and bilateral hilar small lymphadenopathy together with limited granular lesion in the right lung. Gallium-67 scintigraphy demonstrated high uptake not only in mediastinal and hilar lymph nodes but also in bilateral parotid glands. Right parotid gland biopsy revealed noncaseating granulomas and proved pathological diagnosis of sarcoidosis. The systemic symptoms were relieved by oral prednisolone 20 mg daily. Even though the causal relationship remains undetermined, this case is unique at the point that vaccine-associated uveitis led to the detection of pulmonary lesions and lymphadenopathy, resulting in clinical and pathological diagnosis of sarcoidosis. In literature review, 3 patients showed sarcoidosis-like diseases after COVID-19 vaccination: 2 patients were diagnosed clinically as Lofgren syndrome with acute onset of erythema nodosum and ankle swelling, with or without mediastinal and hilar lymphadenopathy, whereas 1 patient with mediastinal lymphadenopathy but no uveitis was diagnosed pathologically by biopsy as sarcoidosis.

File： JIM High Inpact CaseRep Coronavirus vacciation.pdf

DOI： 10.1177/23247096221086450

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Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/23247096221086450

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

File： ijms-22-13276NK-5962.pdf

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File： IgG4 DLBCL.pdf

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The aim of this study is to describe bilateral optic disc swelling in three consecutive patients with Blau syndrome or cryopyrin-associated periodic syndrome at a single institution. Case 1 was a 30-year-old woman receiving 25 mg etanercept twice weekly who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 5 months old and genetically diagnosed with Blau syndrome with CARD15/NOD2 mutation (N670K) at 13 years old. At 10 years old, she began to have uveitis with optic disc swelling in both eyes, resulting in macular degeneration and optic disc atrophy at 17 years old only when etanercept was introduced. Case 2 was a 21-year-old man receiving adalimumab every 2 weeks who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 1.5 years old and genetically diagnosed as Blau syndrome with CARD15/NOD2 mutation (C495Y) at 5 years old. At 8 years old, around the time of adalimumab introduction, he began to show bilateral optic disc swelling which continued until the age of 16 years when the dose of adalimumab was increased. Case 3 was a 20-year-old woman receiving canakinumab every 8 weeks for systemic symptoms such as fever, headache, vomiting, and abdominal pain and later for sensorineural hearing disturbance on both sides. She had been diagnosed genetically with cryopyrin-associated periodic syndrome with NLRP3 mutation (Y859C) at 7 years old. At 5 years old, she was found to have bilateral optic disc swelling, which continued until the age of 10 years when she began receiving canakinumab (IL-1β inhibitor). Bilateral optic disc swelling might be tentatively designated as a plausible common ocular feature, if it occurred, in autoinflammatory diseases to pay more attention to ophthalmic complications in rare diseases.

File： life-11-01433.pdf

DOI： 10.3390/life11121433

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Language：English   Publishing type：Research paper (scientific journal)  

File： materials Letters2021Yamashita.pdf

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File： ZhangJingjing ROP2021 J Ophthalmol.pdf

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File： Alcohol Consumption and AMD.pdf

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)  

File： pharmaceuticals-14-00694-v3.pdf

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NK-5962 is a key component of photoelectric dye-based retinal prosthesis (OUReP). In testing the safety and efficacy, NK-5962 was safe in all tests for the biological evaluation of medical devices (ISO 10993) and effective in preventing retinal cells from death even under dark conditions. The long-term implantation of the photoelectric dye-coupled polyethylene film in the subretinal space of hereditary retinal dystrophic (RCS) rats prevented neurons from apoptosis in the adjacent retinal tissue. The intravitreous injection of NK-5962 in the eyes of RCS rats, indeed, reduced the number of apoptotic cells in the retinal outer nuclear layer irrespective of light or dark conditions. In this study, we reviewed the in vitro and in vivo evidence of neuroprotective effect of NK-5962 and designed pharmacokinetic experiments. The in vitro IC50 of 1.7 μM, based on the protective effect on retinal cells in culture, could explain the in vivo EC50 of 3 μM that is calculated from concentrations of intravitreous injection to prevent retinal neurons from apoptosis. Pharmacokinetics of NK-5962 showed that intravenous administration, but not oral administration, led to the effective concentration in the eye of rats. NK-5962 would be a candidate drug for delaying the deterioration of retinal dystrophy, such as retinitis pigmentosa.

File： life-11-00591.pdf

DOI： 10.3390/life11060591

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File： Prostate Ca2021.pdf

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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File： J Neural Eng2021.pdf

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File： bmm_16_4_045001.pdf

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File： PJ2021OUReP.pdf

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The diagnostic criteria for IgG4-related disease were previously published and serum IgG4 measurement has been reimbursed by national health insurance in Japan since 2012. Eight patients diagnosed with IgG4-related disease based on lacrimal gland masses were retrospectively reviewed. The 8 patients were 3 men and 5 women ranging in age from 52 to 77 (median, 63) years at the initial visit and their follow-up period ranged from 0.25 to 11 (median, 7) years. Bilateral and unilateral involvement were noted in 4 patients each; 2 on the right side and 2 on the left side in those with unilateral involvement. Serum IgG4 was high in 5 of 8 patients at the initial visit. Five patients with no systemic signs were followed without treatment, whereas oral steroids were administered and tapered in the other 3 patients who exhibited systemic signs. One patient with a history of radiation for MALT lymphoma in bilateral lacrimal glands developed IgG4-related disease in the left lacrimal gland 10 years later and was followed without treatment. Nine years later, her serum IgG4 level increased to 1500 mg/dL and paracardiac lesions, found on positron emission tomography, were confirmed to be MALT lymphoma by needle biopsy, leading to systemic chemotherapy. The other 7 patients had neither local recurrence nor additional systemic signs. Serum IgG4 monitoring may be useful to detect systemic complications in IgG4-related ophthalmic disease and markedly high serum IgG4 levels may indicate new lymphoma at other sites.

File： JCEH IgG42021.pdf

DOI： 10.3960/jslrt.20048

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File： JJO 21st century final202106.pdf

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Authorship：Lead author   Language：Japanese  

File： 人工網膜TechnologyRoadMap2021-30.pdf

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

File： 916-Photoelectric dye-based retinal prosthesis (1).pdf

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Authorship：Lead author   Publishing type：Research paper (conference, symposium, etc.)  

File： ATL eye J Invest Med HIgh Inpact Case Rep2020.pdf

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File： jstp-v4-id1040 final20201003.pdf

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Authorship：Lead author   Language：English   Publishing type：Research paper (international conference proceedings)  

File： JIA case J InvestMed High Impact Case Rep2020.pdf

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File： cis-v5-id2903final20200905.pdf

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File： optronics202007人工網膜.pdf

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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File： cis-v5-id2847final20200905.pdf

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File： cis-v5-id2842 final20200630.pdf

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File： 光アライアンス2020;31(7)人工網膜.pdf

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Primary intraocular lymphomas frequently develop into central nervous system lymphomas and vice versa. This study reviewed 22 consecutive patients with primary intraocular lymphoma diagnosed by immunostaining of vitrectomy cell blocks, and examined whether they developed central nervous system lymphoma. Seventeen patients developed central nervous system lymphoma: 3 patients developed intraocular and central nervous system lymphoma simultaneously, 9 patients developed central nervous system lymphoma 1 month to 5 years (median, 3 months) after intraocular lymphoma, and 5 patients developed central nervous system lymphoma preceding the diagnosis of intraocular lymphoma by 3 months to 9 years and 8 months (median, 1.5 years). In contrast, 5 patients did not develop central nervous system lymphoma: 2 patients did not develop local recurrence or central nervous system lymphoma in the follow-up period of 5 years and 11 years, respectively, after vitrectomy alone without additional local or systemic treatment. The remaining 3 patients with intraocular lymphoma had insufficient follow-up periods to determine the prognosis. The results of CD5 immunostaining of vitrectomy specimens were found in pathology reports of 8 patients: 3 patients with CD5-positive large cells and 4 patients with CD5-negative large cells developed central nervous system lymphoma. In summary, only a small number of patients did not develop central nervous system lymphoma based on long-term follow-up after vitrectomy alone. CD5 was not a marker of central nervous system involvement in this study population.

File： JCEH2019final intraocular lymphma.pdf

DOI： 10.3960/jslrt.19019

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File： lacrimal sac melanoma.pdf

DOI： 10.1177/2324709619888052

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Background: Vision plays a key role in some behavior tests for rats. Okayama University-type retinal prosthesis (OUReP) is a photoelectric dye-coupled polyethylene film which generates electric potential in response to light and stimulates nearby neurons. This study aims to assess vision in retinal dystrophic (RCS) rats, in comparison with normal rats, by selected behavior tests. We also examined whether the tests could detect vision changes in RCS rats with dye-coupled film implantation.Methods: Data sets were 5 normal rats, 4 untreated RCS rats, 7 RCS rats with dye-coupled films implanted at the age of 7 weeks after excluding unsuccessful implantation at autopsy. Behavior tests chosen were landing foot splay and visual forelimb-placing response in the menu of functional observational battery, operant-conditioning lever-press response and light/dark box test.Results: Normal visual placing response was significantly less frequent in untreated RCS rats at the age of 9 and 11 weeks, compared with normal rats (P = 0.0027, chi-square test) while normal response was significantly more frequent at the age of 9 weeks in RCS rats with dye-coupled film implantation, compared with untreated RCS rats (P = 0.0221). In operant-conditioning lever-press test, the correct response rate was significantly lower in untreated RCS rats than in normal rats at the age of 9 weeks (P < 0.05, Tukey-Kramer test) while the rate was not significantly different between normal rats and RCS rats with dye-coupled film implantation. In light/dark box test, the time to enter dark box was significantly shorter in normal rats, compared with untreated RCS rats or RCS rats with dye-coupled film implantation (P < 0.05, Tukey-Kramer test).Conclusions: Behavior tests of functional observational battery, operant-conditioning lever-press response and light/dark box test discriminated vision between normal rats and RCS rats. The visual placing response and operant-conditioning lever-press test might have sensitivity to detect vision recovery in RCS rats with OUReP implantation.

File： Heliyon2019 RCSrat.pdf

DOI： 10.1016/j.heliyon.2019.e01936

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE SOC MEDICAL & BIOLOGICAL ENGINEERING  

Electrodes that output electric current as conduction current are widely used to stimulate nerves and cardiac cells in human body. We designed a photoelectric dye-coupled polyethylene film for use as a thin film device to stimulate nerve cells by electric potential changes. The aim of this study was to measure its photo-responsive properties and to record in vitro biological response. When measured using a Kelvin probe system, the photoelectric dye-coupled film showed rapid rise and fall of surface electric potential in response to light-on-and-off. Light-evoked surface electric potential of the dye-coupled film increased in response to increasing light intensity. In vitro biological response to the dye-coupled film was assessed in isolated rat retinal tissues using a multielectrode array recording system. As positive control, electroretinogram-like waves were recorded in response to light from normal rat retinal tissue placed with the inner retinal surface at the bottom of the multielectrode array dish. In contrast, no light-elicited wave was recorded from degenerative retinal tissue isolated from retinal dystrophic Royal College of Surgeons (RCS) rats. When the dye-coupled film was simply overlaid on the degenerative retinal tissue with the inner retinal surface placed at the bottom of the multielectrode array dish, electroretinogram-like waves were elicited in response to light projected from the bottom. Plain polyethylene film without photoelectric dye coupling was used as negative control, and did not yield light-elicited response when placed on the degenerative retinal tissue. For detailed recordings of action potential spikes high-passed at 100 Hz, a nylon mesh anchor was placed on top of the preparation to ensure close contact between the multielectrode array and the retinal tissue with or without the dye-coupled film. In this experimental setting, the degenerative retinal tissue alone showed spontaneous action potential spikes as numerous small trivial amplitudes in the background noise, while the degenerative retinal tissue overlain with the dye-coupled film showed action potential spikes with increased amplitude in response to light against the background of spontaneous spikes. This study confirmed that the photoelectric dye-coupled polyethylene film is able to stimulate degenerative retinal tissue that has lost photoreceptor cells, and may function as a novel type of retinal prosthesis. Electric potential changes, probably as displacement current or capacitive current, may be an alternative approach to stimulate nerves in human body.

File： ABE2019 OUReP.pdf

DOI： 10.14326/abe.8.137

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File： JpnClinMed2019OrbitalMyositis.pdf

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3960/jslrt.18026

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Retinal prosthesis or artificial retina is a promising modality of treatment for outer retinal degeneration, caused by primary and secondary loss of photoreceptor cells, in hereditary retinal dystrophy and age-related macular degeneration, respectively. Okayama University-type retinal prosthesis (OUReP) is a photoelectric dye-coupled polyethylene film which generates electric potential in response to light and stimulates nearby neurons. The dyecoupled films were implanted by vitreous surgery in the subretinal space of monkey eyes with macular degeneration which had been induced by cobalt chloride injection from the scleral side. A pilot 1-month observation study involved 6 monkeys and a pivotal 6-month observation study involved 8 monkeys. Of 8 monkeys in 6-month group, 3 monkeys underwent dye-coupled film removal at 5 months and were observed further for 1 month. The amplitude of visual evoked potential which had been reduced by macular degeneration did recover at 1 month after film implantation and maintained the level at 6 months. Optical coherence tomography showed no retinal detachment, and full-field electroretinograms maintained a-wave and b-wave amplitudes, indicative of no retinal toxicity. Pathological examinations after 6-month implantation showed structural integrity of the inner retinal layer in close apposition to dye-coupled films. The implanted films which were removed by vitrectomy 5 months later showed light-evoked surface electric potentials by scanning Kelvin probe measurement. The photoelectric dye-coupled film (OUReP), which serves as a light-receiver and a displacement current generator in the subretinal space of the eye, has a potential for recovering vision in diseases with photoreceptor cell loss, such as retinitis pigmentosa and age-related macular degeneration.

File： final version Matsuo_et_al-2018-Artificial_Organs.pdf

DOI： 10.1111/aor.13120

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Veterinary Science  

Okayama University-type retinal prosthesis (OURePTM) is a photoelectric dye-coupled polyethylene film which generates electric potential in response to light and stimulates nearby neurons. This study aims to test surgical feasibility for subretinal film implantation and to examine functional durability of films in subretinal space. Dye-coupled films were implanted subretinally by vitrectomy in the right eye of normal white rabbits: 8 rabbits for 1 month and 8 rabbits for 6 months. The implanted films were removed by vitrectomy in 4 of these 8 rabbits in 1-month or 6-month implantation group. The films were also implanted in 4 rhodopsin-transgenic retinal dystrophic rabbits. Visual evoked potential was measured before film implantation as well as 1 or 6 months after film implantation, or 1 month after film removal. The films were successfully implanted in subretinal space of retinal detachment induced by subretinal fluid injection with a 38G polyimide tip. The retina was reattached by fluid-air exchange in vitreous cavity, retinal laser coagulation, and silicone oil injection. The ratios of P2 amplitudes of visual evoked potential in the implanted right eye over control left eye did not show significant changes between pre-implantation and post-implantation or post-removal (paired t-test). In Kelvin probe measurements, 4 pieces each of removed films which were implanted for 1 or 6 months showed proportional increase of surface electric potential in response to increasing light intensity. The film implantation was safe and implanted films were capable of responding to light.

File： JVMS2018 rabbit OUReP.pdf

DOI： 10.1292/jvms.17-0422

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PEERJ INC  

Background/Aim, Strabismus is a common condition with misalignment between two eyes that may lead to decrease of visual acuity, lack of binocularity, and diplopia, It is caused by heterogeneous environmental and genetic risk factors. Our previous research has identified new chromosomal susceptibility loci in 4q28.3 and 7831,2 regions for comitant strabismus in Japanese families, We conducted a verification study by linkage analysis to narrow the chromosomal loci down to a single gene,
Methods. From Japanese and U.S,databases, 24 rsSNPs and 233 rsSNPs were chosen from the 4828,3 and 7831.2 region, respectively, and were typed in 108 affected subjects and 96 unaffected subjects of 58 families with primary and non-syndromic comitant strabismus. Three major analytical methods were used: transmission disequilibrium test (TDT), TDT allowing for errors (TDTae), and linkage analysis under dominant and recessive inheritance.
Results. The SNPs with significant P values in TDT and TDTae were located solely at the gene, microsomal glutathione S-transferase 2 (MGST2), on chromosome 4q28.3 locus. In contrast, significant SNPs were dispersed in a few genes, containing wingless-type MMTV integration site family member 2 ( WNT2), on chromosome 7q31.2 locus. The distribution of significant SNPs on the 7q31.2 locus showed that only the ST7 to WNT2 region in the same big haplotype block contained significant SNPs for all three methods of linkage analysis.
Conclusions. This study suggests that MG ST2 and WNT2 are potential candidates for comitant strabismus in Japanese population.

File： Strabismus SNP PeerJ.pdf

DOI： 10.7717/peerj.3935

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Photoelectric dye-coupled polyethylene film, designated Okayama University type-retinal prosthesis or OUReP (TM), generates light-evoked surface electric potentials and stimulates neurons. The dye-coupled films or plain films were implanted subretinally in both eyes of 10 Royal College of Surgeons rats with hereditary retinal dystrophy at the age of 6 weeks. Visual evoked potentials in response to monocular flashing light stimuli were recorded from cranially-fixed electrodes, 4 weeks and 8 weeks after the implantation. After the recording, subretinal film implantation was confirmed histologically in 7 eyes with dye-coupled films and 7 eyes with plain films. The recordings from these 7 eyes in each group were used for statistical analysis. The amplitudes of visual evoked potentials in the consecutive time points from 125 to 250 ms after flash were significantly larger in the 7 eyes with dye-coupled film implantation, compared to the 7 eyes with plain film implantation at 8 weeks after the implantation (P &lt; 0.05, repeated-measure ANOVA). The photoelectric dye-coupled polyethylene film, as retinal prosthesis, gave rise to visual evoked potential in response to flashing light.

File： Alamusi RCSrat VEP 2017-JAO.pdf

DOI： 10.1007/s10047-016-0943-4

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File： Harada nivolumab.pdf

DOI： 10.1002/ccr3.911

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT, INC  

Purpose: Our previous study demonstrated that photoelectric dye-coupled polyethylene film (Okayama University-type retinal prosthesis), which was implanted in subretinal space of the eyes of Royal College of Surgeons (RCS) rats, prevented retinal neurons from apoptotic death. In this study, we aimed to examine whether photoelectric dye itself would protect retinal neurons from apoptosis in RCS rats.
Methods: RCS rats received intravitreous injection of different concentrations of the dye in the left eye and housed under a 12-h light-dark cycle. Saline injection in the right eye served as control. In addition, RCS rats with dye injection were kept in 24-h daily dark condition. Sections were processed for terminal deoxynucleotidyl transferase-mediated fluorescein-conjugated-dUTP nick-end-labeling (TUNEL) assay and immunohistochemical staining of glial fibrillary acidic protein (GFAP) and protein kinase C alpha (PKC alpha).
Results: The number of TUNEL-positive cells significantly decreased in the retina of dye-injected eyes compared with those in saline-injected eyes (P = 0.0001, 2-factor analysis of variance [ANOVA]), under 12-h light-dark cycle. Significant decrease of TUNEL-positive cells was noted in the retina of rats with dye injection compared with those with saline injection, kept under 24-h dark condition (P = 0.0001, 2-factor ANOVA). Immunoreactive area for GFAP decreased significantly in the retina of dye-injected eyes compared with that in controls (P = 0.0001, 2-factor ANOVA), whereas immunoreactive area for PKCa increased significantly in the retina of dye-injected eyes compared with that in controls (P = 0.01, 2-factor ANOVA).
Conclusions: Photoelectric dye inhibits apoptotic death of photoreceptor cells in RCS rats and downregulates GFAP expression in retinal Muller cells. Photoelectric dye may be a candidate agent for neuroprotection in retinitis pigmentosa and other retinal diseases.

File： Liu NK5962 final jop.2016.0093.pdf

DOI： 10.1089/jop.016.0093

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: The aim of this study is to elucidate background clinical factors in patients with positive bacterial culture for the conjunctival sac before cataract surgery in Japan.
Methods: Retrospective review was made on medical records of 576 consecutive patients who underwent conjunctival sac culture before cataract surgery with night stay at a hospital in 2 years from January 2013 to December 2014. In the patients with sequential bilateral surgeries, the data were chosen for bacterial culture in the eye which had earlier surgery. The age at surgery ranged from 33 to 100 years (mean, 76.7 years). Clinical factors, analyzed in relation with positive or negative bacterial culture, included the sex, the age, the presence of hypertension or diabetes mellitus, history of cancer, and history of hospital-based surgery at other specialties.
Results: Bacterial culture of the conjunctival sac was positive in 168 patients while negative in 408 patients. In multiple regression analysis, the positive bacterial culture was related with the older age (P = 0.01), the presence of diabetes mellitus (P = 0.004), and the history of hospital-based surgery at other specialties (P = 0.001).
Conclusions: Elderly patients with diabetes mellitus or previous hospital-based surgeries at other specialties have a higher rate of positive bacterial culture in the conjunctival sac before cataract surgery. This study would provide a hint for identifying patients at risk for carrying bacterial flora in the conjunctival sac.

File： Conj Sac Culture BMC Ophthalmol2017.pdf

DOI： 10.1186/s12886-017-0413-7

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DOI： 10.3960/jslrt.56.170

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A 42-year-old man with eosinophilia and high serum immunoglobulin E (IgE) developed a lacrimal gland mass on the left side. Excisional biopsy revealed hyperplasia of lymphoid follicles, and infiltration with lymphocytes and eosinophils around lacrimal gland acini, leading to the pathological diagnosis of Kimura disease. IgE-positive cells were mainly found along follicular dendritic cells, and a small number of IgG4-positive cells was present. One month after oral prednisolone was started at 40 mg daily and tapered to 10 mg daily, he developed lower leg edema on both sides and marked proteinuria (10.8 g/day). Renal biopsy showed no glomerular abnormalities, no immunoglobulin deposition, and no tubulointerstitial infiltration with eosinophils, leading to the diagnosis of minimal change nephrotic syndrome. Proteinuria subsided in response to an increased dose of prednisolone to 30 mg daily. Proteinuria relapsed three times in the following 5 years when oral prednisolone was tapered. In conclusion, Kimura disease manifested as an orbital mass and did not relapse. However, nephrotic syndrome relapsed frequently with background eosinophilia and high serum IgE. This study reviewed the clinical features of 10 Japanese patients with Kimura disease associated with proteinuria.

File： Kimura disease Matsuo.pdf

DOI： 10.3960/jslrt.17028

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Veterinary Science  

Okayama University-type retinal prosthesis (OUReP™) is a photoelectric dye-coupled polyethylene film which generates electric potential in response to light and stimulates nearby neurons. This study aims to test surgical feasibility of subretinal implantation and functional durability of dye-coupled films in the subretinal space. The dye-coupled films were implanted subretinally by 25-gauge vitrectomy in the right eye of 11 normal beagle dogs: 2 dogs served for film removal after 5-month film implantation, 3 dogs for film removal after 3-month film implantation, 3 dogs for 3-month film implantation and pathological examination, and 3 dogs for sham surgery. The surface electric potential of the removed dye-coupled films in response to light was measured by the Kelvin Probe system. At surgery, rolled-up dye-coupled films in 5 × 5 mm square size could be inserted into subretinal space of retinal detachment induced by fluid injection with a 38-gauge polyimide tip. Retinal attachment was maintained by silicone oil injection in vitreous cavity. At autopsy, the retina in all dogs maintained the ganglion cell layer, inner and outer nuclear layers while it lost the outer segments in some part. All 5 sheets of removed dye-coupled films maintained the dye color. One sheet of the 5-month implanted film showed proportional increase of surface potential in response to increasing light intensity. Subretinal implantation of OUReP™ by vitrectomy was technically feasible in canine eyes, and OUReP™ maintained the function of generating light-evoked surface potential after 5 months in subretinal implantation.

File： dog surgeryOUReP2017JVMS.pdf

DOI： 10.1292/jvms.17-0450

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER INTERNATIONAL PUBLISHING AG  

Ocular surface or epibulbar dermoid lesions may present as limbal dermoids at the corneal limbus or dermolipomas in the conjunctival fornix. The purpose of this study is to review clinical features of ocular surface dermoids (grade I), with the visual axis unaffected, in pediatric patients, in order to find key features for making clinical decision, either resection or observation. The study involved 13 consecutive patients with limbal dermoids or fornix dermolipomas which did not affect the visual axis, seen in 11 years at a referral-based institution. Eight patients underwent surgical resection at the age, ranging from 1 to 18 (median, 4) years, with concurrent preauricular appendage resection in 3 patients. Limbal dermoids in 6 patients presented dome-shaped elevation from the ocular surface, and extended in inferotemporal quadrant for 1-2 clock hours. The remaining 2 patients showed dermolipomas in the temporal conjunctival fornix. Postoperative astigmatism at the final visit ranged from 0 to 7 (median, 2.9) diopters in 6 patients with limbal dermoids while ranged from 0 to 1 diopters in 2 patients with fornix dermolipomas. All patients with meaningful astigmatism wore glasses before and after the surgery, resulting in no apparent ametropic or anisometropic amblyopia. Observation was chosen in 5 patients with the age at initial visit, ranging from 0 to 2 (median, 1) years, and the age at the final visit, ranging from 2 to 6 (median, 3) years. Flat limbal dermoids, extending for 1-2 clock hours, were noted in 3 patients, a dome-shaped limbal dermoid for 1 clock hour in one, and a fornix dermolipoma in one. Three patients had preauricular appendages. No patient, except for one with a dome-shaped limbal dermoid, showed astigmatism, greater than one diopter. In conclusions, dome-shaped limbal dermoids were excised while flat limbal dermoids observed. The age at surgery varied largely in pediatric patients with limbal dermoids (grade I) or fornix dermolipomas which did not affect the visual axis. The surgical timing was influenced by surgical scheduling for preauricular appendage resection, determined by a plastic surgeon. Surgical decision was made for cosmetic purposes, but not for medical needs to avoid amblyopia.

File： Dermoid Springerplus.pdf

DOI： 10.1186/s40064-015-1326-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Photoelectric dye-coupled polyethylene film, designated Okayama University-type retinal prosthesis or OUReP (TM), generates light-evoked surface electric potentials and stimulates neurons. In this study, the vision was assessed by behavior tests in aged hereditary retinal dystrophic RCS rats with OUReP (TM), retinal apoptosis and electroretinographic responses were measured in dystrophic eyes with OUReP (TM). The dye-coupled films, or plain films as a control, were implanted in subretinal space of RCS rats. On behavior tests, RCS rats with dye-coupled films, implanted at the old age of 14 weeks, showed the larger number of head-turning, consistent with clockwise and anticlockwise rotation of a surrounding black-and-white-striped drum, compared with rats with plain films, under the dim (50 lux) and bright (150 lux) conditions in the observation period until the age of 22 weeks (n = 5, P &lt; 0.05, repeated-measure ANOVA). The number of apoptotic cells in retinal sections at the site of dye-coupled film implantation was significantly smaller, compared with the other retinal sites, neighboring the film, or opposite to the film, 5 months after film implantation at the age of 6 weeks (P = 0.0021, Friedman test). The dystrophic eyes of RCS rats with dye-coupled films showed positive responses to maximal light stimulus at a significantly higher rate, compared with the eyes with no treatment (P &lt; 0.05, Chi-square test). Electroretinograms in normal eyes of Wistar rats with dye-coupled or plain films showed significantly decreased amplitudes (n = 14, P &lt; 0.05, repeated-measure ANOVA). In conclusions, vision was maintained in RCS rats with dye-coupled films implanted at the old age. The dystrophic eyes with dye-coupled films showed electroretinographic responses. Five-month film implantation caused no additional retinal changes.

File： alamusi J Artif Org2015.pdf

DOI： 10.1007/s10047-015-0825-1

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Surgical timing for ectopia lentis has not been well described until now. The purpose of this study is to find a benchmark as to how far observation would be allowed in children with ectopia lentis when they and their families are reluctant to go through surgery. Retrospective review was made on 15 consecutive patients (14 children and one adult) with ectopia lentis in both eyes, seen at a referral-based institution in 5 years from April 2008 to March 2013, to survey the reasons for continuing observation or deciding surgical intervention. The diagnoses were Marfan syndrome in six patients, familial ectopia lentis in six, and sporadic ectopia lentis in three. Observation was continued in nine patients with the age at the final visit, ranging from 4 to 17 (median 9) years, because six children had good visual acuity at both near and distant viewing with glasses, and three children had visual acuity of 0.4 at near viewing despites poor visual acuity at distant viewing with glasses. In contrast, lensectomy was determined in six patients (5 children and one adult) with the age at surgery, ranging from 4 to 36 (median 9) years, and the age at the final visit, ranging from 7 to 42 (median 11) years, mainly because of poor visual acuity at near and distant viewing. More specific causes for surgeries in five children were the optical axis to become aphakic due to the progression of ectopia in the course in two children, lens dislocation to the anterior chamber after blunt eye injury in one child, and difficulty in studying at school classes in two children. One adult patient developed cataract in ectopic lenses. Lensectomy, combined with anterior vitrectomy, was done from two limbal side ports with a 25-gauge infusion cannula and vitreous cutter. Two patients at the age of 16 and 36 years, additionally, underwent intraocular lens-suturing in both eyes. In conclusions, observation was continued in children with ectopia lentis who had good visual acuity at near viewing. The visual acuity at near viewing, 0.4 or better, would give a benchmark for continuing observation in children with ectopia lentis.

File： ectopia lentis Springerplus.pdf

DOI： 10.1186/s40064-015-1239-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER INTERNATIONAL PUBLISHING AG  

The purpose of this study is to know clinical factors underlying either a single surgery or repetitive surgeries, required to treat superior oblique muscle palsy. Retrospective review was made on 246 consecutive patients with idiopathic (n = 212) or acquired (n = 34) superior oblique muscle palsy who underwent surgeries in 8 years at one institution. Idiopathic palsy included congenital and decompensated palsies while acquired palsy included traumatic and ischemic palsies. Clinical factors, compared between groups with a single surgery (n = 203) and two or more surgeries (n = 43), were surgical methods, sex, age at surgery, horizontal, vertical, and cyclotorsional deviations, and stereopsis at near fixation. Inferior oblique muscle recession on paretic side was chosen in about 60% of the single-surgery and repetitive-surgery group as an initial surgery, followed by inferior rectus muscle recession on non-paretic side. The age at surgery was significantly older, vertical and cyclotorsional deviations were significantly larger in the repetitive-surgery group, compared with the single-surgery group (P = 0.01, P &lt; 0.001, P = 0.02, Mann-Whitney U-test, respectively). The 95% confidence interval of vertical deviations was 15-17 prism diopters in the single-surgery group and 23-28 prism diopters in the repetitive surgery group. Significant differences in vertical deviations were replicated also in subgroups of patients with either idiopathic or acquired palsy. In conclusions, the 95% confidence interval of vertical deviations, determined by alternate prism and cover test, would be used as a common benchmark for predicting either a single surgery or repetitive surgeries, required to treat idiopathic and acquired superior oblique muscle palsy, in the process of obtaining the informed consent.

File： Aoba2015_Article_ClinicalFactorsUnderlyingASing.pdf

DOI： 10.1186/s40064-015-0945-3

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DOI： 10.3960/jslrt.55.157

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KEY CLINICAL MESSAGE: We report a case of Behçet's disease which was aggravated by psychological stress and oral infection. The control of oral infection under medical and dental collaboration is important for providing Behçet's disease patients with the optimal medical care and for facilitating the relief of the primary disease.

DOI： 10.1002/ccr3.112

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DOI： 10.3960/jslrt.54.143

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Language：Japanese   Publisher：(株)医学書院  

24歳,女性.両頬の蝶形紅斑と抗核抗体陽性により精査加療目的で当院を受診した.他臓器病変は認めなかった.全身性エリテマトーデス(systemic lupns erythematosus:SLE)と診断しステロイド治療を開始した.順調にテーパリングを行っていたが,治療開始から4ヵ月後に突然眼のかすみと視力低下を自覚し,眼底に綿花様白斑を認めSLE網膜症と診断された.このとき,皮膚症状は改善し血液データの変動もなかった.SLEのさまざまな眼合併症は,通常はSLEの病勢と一致して出現するが,過去9年間の当院のSLE患者の眼合併症の検討では,必ずしも皮膚症状や血液検査データにおけるSLEの病勢とは一致していなかった.SLEの眼合併症を皮疹や臨床検査値などから予測することは困難だが,放置していれば重篤な視力障害につながる危険が高く,注意すべき合併症である.(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J01559&link_issn=&doc_id=20121112150005&doc_link_id=10.11477%2Fmf.1412103457&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1412103457&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：(一社)日本皮膚悪性腫瘍学会  

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

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Language：Japanese   Publisher：(一社)日本皮膚悪性腫瘍学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

DOI： 10.1007/s10047-011-0597-1

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To find optical coherence tomographic parameters related with visual acuity, and, thus, which might be used as objective signs to predict visual acuity after future treatment, for example retinal prosthesis implantation, 86 eyes of 45 consecutive patients with retinitis pigmentosa, who showed no macular diseases, underwent optical coherence tomography to measure macular retinal thickness and peripapillary retinal nerve fiber layer (RNFL) thickness, and to obtain horizontal cross-sectional images at the fovea for observation of the inner segment/outer segment (IS/OS) junction line. Best-corrected visual acuity was significantly better either in the right eyes or in the left eyes with greater retinal thickness of all four quadrants of the macular area in the inner ring, encompassing 1-3 mm from the foveal center (P\\0.05, Spearman rank correlation test), and also with the presence of the IS/OS line at the fovea (P\\0.0001, Wilcoxon-Kruskal-Wallis rank sum test). Retinal average thickness in the posterior pole covering the 6 9 6 mm square area was positively correlated with peripapillary RNFLaverage thickness either in the right eyes or in the left eyes (P\\0.05). The average thickness of the peripapillary RNFLbecame significantly less with age (P\\0.05), but was not related with visual acuity. Macular retinal thickness and the presence of the IS/OS line, but not peripapillary RNFLthickness, could serve as objective signs for better visual acuity in retinitis pigmentosa. The macular retinal thickness might be used as an objective predictor to choose patients with retinitis pigmentosa who would be expected to gain vision after retinal prosthesis implantation. © The Japanese Society for Artificial Organs 2011.

DOI： 10.1007/s10047-011-0557-9

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Language：English   Publisher：The Japanese Society for Lymphoreticular Tissue Research  

The purpose of this study is to determine the relationship of ocular adnexal benign or reactive lymphoid hyperplasia, including orbital pseudotumor, with immunoglobulin G4 (IgG4)-related diseases. Medical charts of 9 consecutive patients with ocular adnexal benign lymphoid lesions, seen in the Department of Ophthalmology, Okayama University Hospital, were reviewed, and pathological sections were restained immunohistochemically for IgG4-, IgG-, and CD138-positive plasma cells. The diagnosis of IgG4-positive lesions was based on 10 or more IgG4-positive plasma cells in a high-power field and greater than 40% ratios of IgG4-positive plasma cells/CD138-positive plasma cells and IgG4-positive plasma cells/IgG-positive plasma cells. IgG4-positive lesions were determined as absent in 5 patients (4 with bilateral lacrimal/orbital lesions and one with a unilateral conjunctival lesion), none of whom showed systemic manifestations. In contrast, IgG4-positive lesions were present in 4 patients (3 with bilateral lacrimal/orbital lesions and one with a unilateral lacrimal/orbital lesion), who showed systemic manifestations : one with Hashimoto thyroiditis, one with IgG4-positive bilateral interstitial lung disease and hepatic inflammatory pseudotumor, one with bilateral interstitial lung disease, and one with systemic lymphadenopathy and antiphospholipid syndrome. In conclusion, IgG4-positive ocular adnexal benign lymphoid lesions might be used as a benchmark for the probable presence of other systemic lymphoid lesions.

DOI： 10.3960/jslrt.50.129

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Other Link： http://search.jamas.or.jp/link/ui/2011254628

Language：English   Publisher：The Japanese Society for Lymphoreticular Tissue Research  

The purpose of this study is to show that the histopathological type of an orbital lymphoma can differ from the systemic follicular lymphoma that precedes it. A 44-year-old man (Patient #1) and a 50-year-old man (Patient #2) presented with generalized lymphadenopathy due to grade 1 follicular lymphoma proven on lymph node biopsy. Patient #1 was followed without treatment for 16 years when he developed a right orbital mass. Patient #2 underwent several courses of combination chemotherapy as well as radiation but relapsed. The second biopsy of the lymph node nine years later showed the same histopathological type of follicular lymphoma. He developed an orbital mass on the right side 16 years after the initial presentation. In Patient #1, excisional biopsy of the orbital masses showed extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). In Patient #2, biopsy revealed the orbital mass to be T-cell/histiocyte-rich diffuse large B-cell lymphoma. In Patient #1, when comparing the original lymph node biopsy to the orbital biopsy obtained years later, no evidence for clonality was noted by polymerase chain reaction. In Patient #2, the amplification by polymerase chain reaction of the immunoglobulin heavy chain gene rearrangement in the lymph node lesion and the orbital lesion gave rise to a single discrete band with the same DNA sequence except for five nucleotide changes, indicating the same clonality in the presence of genomic changes. In conclusion, orbital lymphomas can occur as a second lymphoma with a different histopathological type in the long-term follow-up of systemic lymphomas. The original and subsequent lymphomatous lesions may or may not share neoplastic cell clonality and all genomics. [J Clin Exp Hematopathol 48(1) : 17-24, 2008]

DOI： 10.3960/jslrt.48.17

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Other Link： http://search.jamas.or.jp/link/ui/2008264833

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

We analyzed nucleotide changes in 3 genes, ARIX, PHOX2B, and KIF21A, in 6 patients of 3 families with congenital superior oblique muscle palsy. Three exons of ARIX, 3 exons of PHOX2B, and exons 8, 20, and 21 of KIF21A were amplified by polymerase chain reaction from genomic DNA isolated from the peripheral blood. The DNA fragments were directly sequenced in both directions. In 2 different families, a heterozygous nucleotide change, ARIX 153G &gt; A, in the 5'-untranslated region was found in common between a father and daughter with muscle palsy and between a mother and daughter with muscle palsy (Family No. I and No. 3). In the other family (Family No. 2), a heterozygous 15-nucleotide deletion, PHOX2B 1124del15, resulting in loss of 5 alanine residues in the alanine repeat of the protein, was found in the daughter with muscle palsy and her father with normal traits, but was not found in the mother with muscle palsy. No KIF21A nucleotide change was found in any patients. The ARIX 153G &gt; A polymorphism might be a genetic risk factor for the development of congenital superior oblique muscle palsy.

DOI： 10.18926/AMO/30985

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Other Link： http://search.jamas.or.jp/link/ui/2007235727

Language：Japanese   Publishing type：Research paper (scientific journal)  

Patients with retinitis pigmentosa lose photoreceptor cells by genetic abnormalities and hence become blind. Neurons such as bipolar cells and ganglion cells still remain alive even in the retina of these patients, and ganglion cells send axons to the brain as the optic nerve. The replacement of dead photoreceptor cells with something artificial is the basic concept of retinal prostheses. The remaining retinal neurons can be stimulated by either electric current or electric potential. Photodiode array and electrode array are two main ways to stimulate retinal neurons as retinal prostheses. These retinal prostheses have problems such as low sensitivity and requiring outer electric sources (batteries). To overcome the problems, we are developing photoelectric dye-based retinal prostheses which absorb light and convert photon energy to electric potentials. The prototype, photoelectric dye-coupled polyethylene film, could generate intracellular calcium elevation in photoreceptor-lacking retinal tissues and also in cultured retinal neurons. The photoelectric dye-based retinal prostheses are thin and soft, and therefore, a sheet of the film in a large size, corresponding to wide visual field, can be inserted into the vitreous and then to the subretinal space through a small opening by rolling up the film. After the production control and the quality control have been established, clinical trials of the photoelectric dye-based retinal prostheses would be planned in concordance with the Drugs and Medical Devices Law to prove the safety and the efficacy.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

All children at the age of 1.5 and 3 years in Japan undergo physical, mental, and developmental checkups including dental, eye, and hearing examinations. The vision-screening program consists of 3 steps: questionnaires and home visual acuity testing as the first step (only for 3-year-old children), visual acuity testing by nurses and inspection by medical officers at regional Health Centers as the second step, and detailed examinations by ophthalmologists as the third step. This study aims to reveal the prevalence of strabismus and amblyopia as obtained from data in the vision-screening program. The final diagnoses made by ophthalmologists and sent back to the Health Centers in Okayama City were reviewed to elucidate the prevalence of strabismus, amblyopia, refractive errors, and other diseases in 1.5- and 3-year-old children in Okayama City in 5 years from 2000 to 2004. Of approximately 6,500-6,900 total children, 83.7-86.8% at 1.5 years old and 77.8-81.9% at 3 years old were brought to the Health Centers. The rates of strabismus were 0.01-0.12% at 1.5 years old and 0.20-0.34% at 3 years old, while the rates of amblyopia were 0% at 1.5 years old and 0.13-0.18 % at 3 years old. The higher rates of strabismus at 3 years old were attributed mainly to the increase of exotropia and intermittent exotropia. In conclusions, the prevalence of strabismus was different between 1.5- and 3-year-old children. The vision-screening program in Japan functions to detect strabismus and amblyopia.

DOI： 10.18926/AMO/32910

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT INC PUBL  

To understand the role of prostaglandins F-2alpha, and E-2 in aqueous humor under the normal condition, their concentrations were measured by enzyme immunoassay in aqueous fluid obtained from either eye of 60 patients during cataract surgery and correlated with clinical factors as the age and intraocular pressure. The concentrations of prostaglandin F-2alpha in the aqueous of all patients were below the level of detection. The concentrations of prostaglandin E-2 in the aqueous were below the level of detection in 37 patients while ranged from 9 to 48 pg/mL (median, 31) in 23 patients. The levels of prostaglandin E-2 did not have correlation with the age of the patients or the intraocular pressure of the eyes. In conclusions, the concentrations of prostaglandin E-2 were apparently higher than the concentrations of prostaglandin F-2alpha in the aqueous. This study could not prove the relationship between prostaglandin levels and the intraocular pressure or the age.

DOI： 10.1089/108076804773710768

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：B M J PUBLISHING GROUP  

Aim: To identify ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy and to find the relation between the ARIX gene and congenital superior oblique muscle palsy.
Methods: The three exons of the ARIX gene were sequenced by genomic DNA amplification with polymerase chain reaction (PCR) and direct sequencing in 15 patients with superior oblique muscle palsy (13 with congenital and two with acquired palsy) and 54 normal individuals. PCR products cloned into plasmids were also sequenced. A family with father and a daughter each having congenital superior oblique muscle palsy was also involved in this study.
Results: Four patients with congenital superior oblique muscle palsy carried heterozygous nucleotide changes in the ARIX gene. One patient with the absence of the superior oblique muscle had T7C in the 5'-UTR of the exon 1 and C-44A in the promoter region, both of which were located on the same strand. Another unrelated patient with congenital superior oblique muscle palsy had C76G in the 5'-UTR of the exon 1 and C-9A in the promoter region on the same strand. G153A in the 5'-UTR of exon 1 was found in common in two affected members of a family with congenital superior oblique muscle palsy. This G153A in the 5'-UTR of exon 1 was also present in four unrelated normal individuals. No other heterozygous nucleotide changes were found in normal individuals.
Conclusions: The nucleotide change (G153A) in the 5'-UTR of exon 1 co-segregated with congenital superior oblique muscle palsy in one family. Four other nucleotide changes in the exon 1 or the promoter region were found only in patients with congenital superior oblique muscle palsy. These nucleotide polymorphisms may be one of the risk factors for the development of congenital superior oblique muscle palsy.

DOI： 10.1136/bjo2003.021527

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Photoelectric dyes absorb light and convert photon energy to electric potentials. To test whether these dyes could be used for retinal prostheses, a simple in vitro screening system was developed. Retinal neurons were cultured from the eyes of chick embryos at the 10-day embryonic stage, at which time no retinal photoreceptor cells have yet developed. Intracellular calcium elevation was observed with Fluo-4 in cultured retinal neurons before and after photoelectric dye was applied at varying concentrations to the culture medium. Five of 7 photoelectric dyes tested in this in vitro system induced intracellular calcium elevation in cultured chick retinal neurons. The intracellular calcium elevation generated by the 5 photoelectric dyes was blocked by extracellular calcium depletion in the case of all 5 dyes, and, except for one dye, by the presence of voltage-gated calcium channel blockers. The photoelectric dyes absorbed light under an inverted microscope and stimulated retinal neurons. This simple in vitro system allows the screening of photoelectric dyes which can be used for retinal prostheses.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

The purpose of this study was to elucidate the role of extracellular matrix components such as aggrecan, fibronectin, and laminin in the extraocular muscle of patients with strabismus. Resected tissues of the medial rectus muscle of 47 patients with intermittent exotropia obtained during recession-resection surgery were frozen under liquid nitrogen and pulverized by a Freezer/Mill to solubilize the tissue for enzyme immunoassay. The total amounts of aggrecan, fibronectin, and laminin in the resected tissue were correlated with clinical data of patients such as age, exodeviation, and refractive error. The amount of aggrecan decreased significantly with the advance of age (P &lt; 0.0001, Spearman rank correlation test), while the amount of laminin or fibronectin had no correlation with age. Patients with basic type intermittent exotropia showed larger, although not significantly, amounts of aggrecan than those with convergence insufficiency type (P = 0.0538, Mann-Whitney U-test). The amount of aggrecan may be related to motor aspects of intermittent exotropia.

DOI： 10.18926/AMO/32803

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

The purpose of this study was to search for chromosomal susceptibility loci for comitant strabismus. Genomic DNA was isolated from 10 mL blood taken from each member of 30 nuclear families in which 2 or more siblings are affected by either esotropia or exotropia. A genome-wide search was performed with amplification by polymerase chain reaction of 400 markers in microsatellite regions with similar to10 cM resolution. For each locus, non-parametric affected sib-pair analysis and nonparametric linkage analysis for multiple pedigrees (Genehunter software, http://linkage. rockefeller.edu/soft/) were used to calculate multipoint lod scores and non-parametric linkage (NPL) scores, respectively. In sib-pair analysis, lod scores showed basically flat lines with several peaks of 0.25 on all chromosomes. In non-parametric linkage analysis for multiple pedigrees, NPL scores showed one peak as high as 1.34 on chromosomes 1, 2, 4, 7, 10, 15, and 16, while 2 such peaks were found on chromosomes 3, 9, 11, 12, 18, and 20. Non-parametric linkage analysis for multiple pedigrees of 30 families with comitant strabismus suggested a number of chromosomal susceptibility loci. Our ongoing study involving a larger number of families will refine the accuracy of statistical analysis to pinpoint susceptibility loci for comitant strabismus.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SWETS ZEITLINGER PUBLISHERS  

Purpose: To describe bilateral optic neuritis that occurred as an adverse effect of recombinant and natural interferon a administration. Methods: Report of two cases. Case 1, a 62-year-old woman, developed bilateral optic neuritis with decreased sensation of vibration and increased deep tendon reflex in the lower extremities after a seven-month use of recombinant interferon alpha-2a for chronic active hepatitis C. Case 2, a 29-year-old woman, developed bilateral optic neuritis combined with numbness of the lower extremities as well as bowel and bladder dysfunction after a 22-month use of recombinant interferon alpha-2b for chronic myelogenous leukemia. After a two-month interruption of interferon administration, natural interferon a was given but followed by another episode of the same neurological manifestations. Results: In both cases, magnetic resonance imaging demonstrated multiple small high-intensity areas in the cerebral white matter and spinal cord, while cerebrospinal fluid examination disclosed mononuclear cell increase and protein elevation including myelin basic protein, all of which simulated the features of multiple sclerosis. The two patients underwent several courses of pulse corticosteroid therapy, each course consisting of three days of methylprednisolone 1000 mg daily, resulting in visual recovery to some extent. Conclusions: Optic neuritis in combination with other neurological signs, simulating multiple sclerosis, should be included in the list of adverse effects of recombinant and natural interferon a administration.

DOI： 10.1076/ocii.10.4.299.15588

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SWETS ZEITLINGER PUBLISHERS  

Purpose: To explore the role of human herpesvirus-8 (HHV-8) in the pathogenesis of uveitis and other forms of ocular inflammation. Methods: Serum antibody titers to HHV-8 were measured in 76 patients with uveitis from various causes and other types of ocular inflammation in either the acute phase, the convalescent phase, or both. Results: Only one 21-year-old male patient in the convalescent phase of unilateral pars planitis showed a positive titer for HHV-8. His serum was negative for human immunodeficiency virus-I. Conclusions: Although the seropositive rate in the patient population was higher than that in the general population, the increased incidence was not statistically significant. The role of HHV-8 in the pathogenesis of intraocular inflammation appears to be limited.

DOI： 10.1076/ocii.10.3.197.15602

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SWETS ZEITLINGER PUBLISHERS  

Purpose: To present submacular exudates as a manifestation of cat scratch disease. Methods: Report of two cases. Results: The first patient, a 34-year-old man, developed submacular exudates with serous retinal detachment ten days after having axillary lymphadenopathy and fever. The second patient, a 30-year-old woman, developed submacular exudates with serous retinal detachment mimicking central serous chorioretinopathy. Fluorescein angiography revealed late staining of the subretinal lesions in both cases. The lesion resolved spontaneously in the first patient, while sulfamethoxazole and trimethoprim was required for the second patient. Both patients had a positive IgG titer for Bartonella henselae. Conclusions: Submacular exudates with serous retinal detachment can occur in cat scratch disease. Cat scratch disease should be included in the differential diagnosis of submacular exudates with central serous chorioretinopathy.

DOI： 10.1076/ocii.10.2.147.13979

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BRITISH MED JOURNAL PUBL GROUP  

Aims: To describe the results of a study of the incidence of conjunctival ulceration and its pathology as a manifestation of Behcet's syndrome.
Methods: The authors reviewed retrospectively medical charts of 152 patients with Behcet's syndrome seen at the uveitis service of Okayama University Hospital from January 1995 to December 1999. Criteria used to diagnose Behcet's syndrome in this study required the presence of oral aphthous ulceration plus any two of three other manifestations-genital ulceration, eye lesions such as iridocyclitis uveoretinitis, or skin lesions such as erythema nodosum. The presence of conjunctival ulceration was determined in patients with Behcet's syndrome through standardised ophthalmological examinations. A biopsy of the conjunctival ulceration was performed in one patient. The incidence of conjunctival ulceration in patients with Behcet's syndrome was calculated and the clinical and pathological features of this ulceration were examined.
Results: Four of 152 patients (2.6%) developed conjunctival ulceration in concordance with exacerbation of their systemic symptoms. Histopathological examinations of a conjunctival biopsy specimen in one patient revealed intraepithelial and perivascular infiltration with neutrophils and lymphocytes consistent with Behcet's syndrome. The conjunctival ulcerations of the study patients showed good response to topical corticosteroids or topical steroids plus oral colchicine.
Conclusions: Conjunctival ulceration should be noted as an uncommon but possible manifestation of Behcet's syndrome. Accordingly, routine examination of the conjunctival is recommended in patients with Behcet's syndrome, and Behcet's syndrome should be included in a list of differential diagnoses for patients with conjunctival ulcerations.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC  

To understand molecular mechanisms of retinal development, genes expressed selectively only in the early stage of retinal development were isolated by subtractive hybridization based on suppression polymerase chain reaction. The retina has no layered structure in 7-day chick embryos, in contrast with the fully developed multilayered structure of neurons in 15-day embryos. The subtraction between cDNA derived from retinal tissues at these different stages, followed by repeat rounds of 5'-RACE (rapid amplification of cDNA ends) and 3'-RACE, led to isolation of a novel gene with an open reading frame encoding a putative protein with 753 amino acids. Its specific expression in the 7-day embryonic retina was confirmed by Northern blot analysis. The gene, named "retinovin," would be used as a marker for identifying retinal stem cells present at the early stage of retinal development. (C) 2000 Academic Press.

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Purpose: This study aimed to determine whether indocyanine green (ICG) angiography is useful to identify the ingrowth site of idiopathic choroidal neovascularization (CNV), which can predict visual outcomes after surgical removal of idiopathic CNV. Design: Consecutive, observational case series. Participants: Twenty-six patients with idiopathic subfoveal CNV, of whom six underwent submacular surgery. Intervention: Indocyanine green videoangiography with a scanning laser ophthalmoscope. Main Outcome Measures: We studied ICG videoangiographic images of choroidal neovascular membranes from the early phase to the late phase with special attention to abnormal findings, which can indicate the ingrowth site of CNV. Results: Early ICG angiography demonstrated distinct neovascular vessels in 24 of the 26 patients (92%). Hypofluorescent rims continuously or intermittently surrounded neovascular membranes on late ICG angiograms in 21 of the 26 patients (81%). In 22 of the 26 patients (85%), ICG angiography demonstrated hypofluorescent areas within the CNV. These hypofluorescent areas frequently became ring shaped in the middle to late phase of the ICG angiography. In 14 of 16 patients (88%) with CNV larger than half a disc area, the filling of neovascular vessels appeared from the inside of the hypofluorescent areas and branched out toward the surrounding hyperfluorescent membrane in the early phase. In all six patients who underwent surgical removal of CNV, ICG videoangiography showed these hypofluorescent areas from which neovascular vessels emanated. Three of the four surgical patients, in whom hypofluorescent areas or central fluorescent areas surrounded by ring-shaped hypofluorescence were extrafoveal or juxtafoveal, had a best postoperative visual acuity of 20/60 or better. In contrast, both surgical patients with subfoveal hypofluorescent areas had a best postoperative visual acuity of 20/70 or worse. Conclusions: Although further observations are needed, ICG angiography may be a useful adjunct in the identification of the ingrowth site of idiopathic CNV, which can predict visual outcomes after surgery. (C) 2000 by the American Academy of Ophthalmology.

DOI： 10.1016/S0161-6420(99)00126-8

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PURPOSE: To report the visual outcome of surgical treatment of submacular hemorrhage associated with idiopathic polypoidal choroidal vasculopathy. METHODS: Eight eyes of eight consecutive patients with thick submacular hemorrhages associated with idiopathic polypoidal choroidal vasculopathy were treated with pars plana vitrectomy and tissue plasminogen activator-assisted removal of subretinal blood (December 1995 to September 1997) or intravitreal 100% sulfur hexafluoride gas injection without tissue plasminogen activator (October 1997 to March 1998). RESULTS: Postoperatively, laser treatment was performed for active polypoidal lesions outside the foveal avascular zone in four eyes. A retinal pigment epithelial tear was seen outside the foveal avascular zone in three eyes, and one eye developed a retinal detachment. The best-corrected visual acuity improved (by 3 or more lines) or stabilized in seven of the eight eyes. Four eyes had a final best- corrected visual acuity of 20/40 or better, and three eyes had a final best- corrected visual acuity of 20/50 to 20/200. In one eye, the visual acuity decreased from 20/100 to 20/500 because of the development of a subfoveal neovascular membrane. The membrane was excised, and histologic examination showed fibrovascular tissue between the retina and retinal pigment epithelium (type 2 pattern). CONCLUSIONS: Surgical intervention may be of benefit in eyes with submacular hemorrhage associated with idiopathic polypoidal choroidal vasculopathy.

DOI： 10.1016/S0002-9394(99)00078-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Academic Press Inc.  

To understand molecular mechanisms underlying the response to pressure in human trabecular cells of the eye, genes induced by cyclic mechanical stretching were isolated by subtractive hybridization assisted by polymerase chain reaction. A novel gene containing an Alu repetitive element in the 5' untranslated region was identified, and its expression was confirmed by Northern blot analysis to be stretch-specific in trabecular cells. The gene was also expressed in the retina, but not in the other tissues, including the brain. The gene encoded a putative small protein with 44 amino acids, which showed homology with neuromedin K. The putative novel protein was named as 'oculomedin,' and would be used as a candidate gene for glaucoma.

DOI： 10.1006/bbrc.1999.0797

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OBJECTIVE: To examine choroidopathy in patients with Behçet disease. DESIGN: Prospective clinical study. PARTICIPANTS: Thirty-three patients (63 eyes) with Behçet disease. INTERVENTION: Patients underwent simultaneous indocyanine green (ICG) and fluorescein angiography with a double detector of scanning laser ophthalmoscopy. MAIN OUTCOME MEASURES: Angiographic findings recorded on videotapes were evaluated. The relation of angiographic findings with systemic activity and aqueous inflammation was also analyzed. RESULTS: Fluorescein angiography showed leakage in varying degrees from retinal vessels in 30 patients (53 eyes, 84%). The ICG angiographic findings were choroidal vascular wall staining in 16 eyes (25%), hyperfluorescent spots in 42 eyes (66%) and hypofluorescent plaques in 22 eyes (35%), both of which were not evident with fluorescein, leakage from choroidal vessels in 3 eyes (5%), and irregular filling of choriocapillaris in 11 eyes (17%). These findings did not have a statistically significant correlation with the presence or absence of aqueous inflammation or oral aphthous ulcerations. CONCLUSIONS: The patients with Behçet disease showed choroidal abnormalities, which could be revealed only by ICG angiography, but not with funduscopy or fluorescein angiography. Simultaneous ICG and fluorescein angiography would be useful for examining choroidal lesions in Behçet disease.

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AIMS: The authors studied how artificially damaged Bruch's membrane influenced growth and differentiation of transplanted embryonic retinal pigment epithelial (RPE) cells and of host RPE cells in rabbits. METHODS: Embryonic RPE cells obtained from pigmented rabbits were transplanted into the subretinal space of adult albino rabbits. The host RPE was removed with a silicone cannula, and Bruch's membrane was damaged by scratching with a microhooked 27 gauge needle under the detached retina in closed vitrectomy. The transplantation sites were examined 3, 7, and 14 days after surgery by light and electron microscopy. RESULTS: Varying degrees of damage in Bruch's membrane were observed. Pigmented and hypopigmented RPE cells showed a normal polarity and tight junctions were seen at the sites of mild to moderate damage 3-7 days after the surgery. In contrast, fibroblast-like cells with no such features of RPE cells formed multiple layers at the sites of severe damage involving the full thickness of Bruch's membrane and the choriocapillaris even 14 days after the surgery. Without transplantation, host RPE cells repopulated the damaged areas in the same way as transplanted RPE cells. CONCLUSIONS: Transplanted embryonic RPE cells as well as host RPE cells grew and differentiated on the moderately damaged Bruch's membrane, while the severely damaged Bruch's membrane did not allow differentiation of RPE cells although these cells could grow and cover the damaged areas.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Both long posterior ciliary arteries were occluded or the three extraocular muscles were tenotomized to produce anterior segment ischemia in rabbits, and the aqueous levels of vascular endothelial growth factor (VEGF) were measured. The occlusion of both long posterior ciliary arteries led to clinical and histological anterior segment ischemia in varying degrees. The aqueous VEGF levels increased significantly compared with controls on all days examined (Mann-Whitney U test: day 1, P = 0.0039; day 4, P = 0.0065; day 7, P = 0.0039; day 14, P = 0.0104), while the levels at days 7 and 14 decreased significantly compared with those at day 4 (Wilcoxon signed-rank test; day 4 to day 7 and day 4 to day 14, P = 0.0464). In contrast, tenotomy of the three extraocular muscles resulted in no histological changes. The VEGF levels increased significantly compared with controls at day 1 and day 4 after surgery (Mann-Whitney U test: day 1 and day 4, P = 0.0104), while the levels at day 14 decreased significantly compared with those at day 1 (Wilcoxon signed-rank test, P = 0.0499). Aqueous VEGF levels represent the severity of anterior segment ischemia and could be used as an indicator for the extent of ischemia. (C) 1998 Japanese Ophthalmological Society.

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Bovine trabecular cells in growth phase were exposed to cyclic mechanical stretching of the bottom of a culture dish at a cycle of 30 seconds for 72 hours, The stretched cells produced significantly larger amounts of metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) after 72 hours, compared with cells in nonstretched control. In contrast, TIMP-2 and MMP-9 levels were not influenced by mechanical stretching. Trabecular cells would modify extracellular matrix in response to such mechanical stimuli as bending of trabecular meshwork or aqueous flow by the production of TIMP-1 and MMP-2. (C) 1998 Japanese Ophthalmological Society.

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A 37-year-old man developed geographic choroiditis and retinal vasculitis in the left eye while taking 3.5 mg/day oral prednisolone for rheumatoid arthritis. The choroidal lesions stopped growing when the dose of prednisolone was increased to 60 mg/day, while its tapering resulted in the recurrence and enlargement of the choroidal lesions to the macula. The patient experienced further recurrence twice in the following year. Indocyanine green angiography demonstrated the obstruction of choroidal arteries in addition to the complete obstruction of the choriocapillaris in a fresh lesion. This case was the first to have geographic choroiditis on the background of a systemic inflammatory disease.

DOI： 10.1016/S0021-5155(97)00102-0

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A 72-year-old Japanese woman, suffering from squamous cell lung cancer with brain metastasis, underwent 2 courses of combination chemotherapy, consisting of cisplatin and vindesine. Although both the primary tumor and the brain metastasis regressed markedly, she developed left ocular pain with blurred vision. An abnormal mass was found in the left iris, and cytologic examination of the aqueous aspirate revealed a few malignant cells, which, when examined by electron microscopy, were considered to be derived from squamous cell carcinoma of the lung.

DOI： 10.1007/BF02489914

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Inc.  

Purpose: The authors present clinical features of 18 juvenile patients with a new type of uveitis termed bilateral iridocyclitis with retinal capillaritis (BIRC). Methods: The authors reviewed medical records of 18 consecutive patients who showed bilateral iridocyclitis with retinal capillary leakage but no systemic manifestations during an 11-year period from January 1985 to December 1995. Results: Twelve of the 18 patients were female and the age at onset ranged from 9 to 17 years old. All patients had many cells in the anterior chamber and anterior vitreous, together with mutton fat keratic precipitates. Fluorescein angiography showed leakage from the optic disc and retinal capillaries, mainly in the midperiphery, which corresponded to retinal cloudiness. Macular edema was minimal, and all patients maintained good vision. The inflammation responded well to topical, oral, and intravenous administration of corticosteroids, the choice of which was based on the extent of retinal inflammation. Human leukocyte antigen (HLA)-DR6 and HLA-Cw7 were associated significantly with the presence of BIRC (chi square test, P &lt
0.0001). Conclusions: Bilateral retinal capillaritis affecting capillaries in various areas of the retina and overlying retinal cloudiness with no distinct lesions are unique to these patients. Fluorescein angiography is essential for diagnosis of BIRC.

DOI： 10.1016/S0161-6420(97)30203-6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN J OPHTHALMOL  

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Retinol-binding protein (RBP) is a plasma protein with a molecular weight of 21,000 synthesized in the hepatocytes, binds with retinol (vitamin A), and transports it to peripheral tissues. Keratomalacia is caused by deficiency of vitamin A itself and/or protein-calorie malnutrition in the latter of which production of RBP is inhibited. We found for the first time familial hypo-retinol-binding proteinemia in a child at an age of 19 months who developed keratomalacia during measles infection in spite of good nourishment. The patient, her sister and mother showed persistent low levels, about half the normal levels of retinol and RBP which were unresponsive to oral vitamin A and protein diet. But they had normal liver function tests, normal levels of the other serum proteins, lipids, and fat-soluble vitamins. This hypo-retinol binding proteinemia was thought to predispose the child to develop keratomalacia during measles. The family members involved would be heterozygous for the normal gene and the defective gene of RBP.

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A 44-year-old man was seen as having acute retinal necrosis syndrome involving both eyes at an interval of 3 years. The cement-like exudates typical to this disease were observed in the fundus of both eyes
they were self-limiting, finally resulting in retinochoroidal degeneration without retinal detachment before becoming confluent. The patient showed an elevation of the convalescent antibody titer to varicella-zoster virus in the aqueous humor during the second eye involvement. We suggest that there exists a self-limiting mild type of acute retinal necrosis syndrome of which the present case is an example.

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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File： OUReP Injector Animal Eye Res 原著-比較眼科研究Vol37.pdf

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DOI： 10.3960/jslrt.56.170

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Language：Japanese   Publisher：日本工業出版  

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Language：Japanese   Publisher：日本皮膚科学会-西部支部  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

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Language：English   Publisher：MOSBY-ELSEVIER  

DOI： 10.1016/j.ajodo.2016.03.002

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DOI： 10.4044/joma.127.223

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DOI： 10.3960/jslrt.55.157

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Language：English   Publisher：SPRINGER INTERNATIONAL PUBLISHING AG  

Purpose: To describe the incidence of unilateral congenital cataract associated with minimal (ultrasonically undetectable) levels of persistent fetal vasculature in the first 18 months of the life and to report surgical methods for intraocular lens implantation, using 25-gauge vitrectomy system.
Methods: Retrospective review was made on 16 consecutive patients with bilateral or unilateral congenital cataract in the first 18 months of the life who underwent surgery at Okayama University Hospital after the introduction of the 25-gauge vitrectomy system from October 2005 to March 2013. As the standard of care at this hospital in the study period, intraocular lenses were not implanted in children with bilateral cataract while intraocular lenses were implanted in those with unilateral cataract.
Results: Ten children with bilateral cataract underwent lensectomy in both eyes with a 25-gauge vitreous cutter under irrigation with a 25-gauge infusion cannula, inserted from two side ports at the corneal limbus. Six children with unilateral cataract underwent intraocular lens implantation and posterior capsulotomy after lens aspiration from limbal side ports. No patient showed vitreous abnormalities on ultrasound examinations before the surgery. At the surgery, all 10 children with bilateral cataract showed no additional abnormalities. In contrast, 3 children with unilateral cataract at the age younger than 12 months showed white fibrous tissue in the anterior vitreous integrated with the posterior lens capsule while the other 3 children with unilateral cataract at the age from 12 to 18 months did not have vitreous abnormalities. The fibrous tissue was cut together in the process of posterior capsulotomy from a 25-gauge trocar inserted at 1.5 mm posterior from the corneal limbus.
Conclusions: Unilateral congenital cataract in the first 12 months of the life has a high incidence for the association with anterior type of persistent fetal vasculature which could not be detected by preoperative ultrasound examinations. Intraocular lens implantation was technically feasible in unilateral cataract with or without minimal levels of persistent fetal vasculature in the first 18 months of the life.

File： congenital cataract Springerplus.pdf

DOI： 10.1186/2193-1801-3-361

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Purpose: Glass transition temperature is a main indicator for amorphous polymers and biological macromolecules as materials, and would be a key for understanding the role of trehalose in protecting proteins and cells against desiccation. In this study, we measured the glass transition temperature by differential scanning calorimetry of dried lens tissues as a model of a whole biological tissue to know the effect of pretreatment by trehalose and other sugars.
Methods: Isolated porcine lenses were incubated with saline, 100 or 1000 mM concentration of trehalose, maltose, or cyclic tetrasaccharide dissolved in saline at room temperature for 150 minutes. The solutions were removed and all samples were dried at room temperature in a desiccator until no weight change. The dried tissues were ground into powder and placed in a measuring pan for differential scanning calorimetry.
Results: The glass transition temperature of the dried lens tissues, as a mean and standard deviation, was 63.0 +/- 6.4 degrees C (n = 3) with saline pretreatment; 53.0 +/- 0.8 degrees C and 56.3 +/- 2.7 degrees C (n = 3), respectively, with 100 and 1000 mM trehalose pretreatment; 56.0 +/- 1.6 degrees C and 55.8 +/- 1.1 degrees C (n = 3), respectively, with 100 and 1000 mM maltose pretreatment; 60.0 +/- 8.8 degrees C and 59.2 +/- 6.3 degrees C (n = 3), respectively, with 100 and 1000 mM cyclic tetrasaccharide pretreatment. The glass transition temperature appeared lower, although not significantly, with trehalose and maltose pretreatments than with saline and cyclic tetrasaccharide pretreatments (P &gt; 0.05, Kruskal-Wallis test). The glass transition temperature of the dried lens tissues with trehalose pretreatment appeared more noticeable on the thermogram, compared with other pretreatments.
Conclusions: The glass transition temperature was measured for the first time in the dried lens tissues as an example of a whole biological tissue and might provide a basis for tissue preservation in the dried condition.

DOI： 10.1186/2193-1801-3-317

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The purpose of this study was to redefine the role of whole-body 2-[F-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography fused with computed tomography (PET/CT) in the clinical diagnosis of choroidal malignant melanoma.
The study design was a retrospective case series involving 7 consecutive patients with choroidal malignant melanoma who underwent enucleation to reach the final pathological diagnosis. FDG-PET/CT was performed together with magnetic resonance imaging and ophthalmological examinations before the surgery. The area, thickness, longest diameter, and circumference of the tumor mass were measured on pathological sections, and were correlated with maximum standardized uptake values (SUVmax) of the tumors on FDG-PET/CT.
Abnormally high uptake of FDG was noted in the affected eyes of 5 patients, but not in the eyes of 2 patients. The 5 patients with high uptake showed nodular tumors extruding into the vitreous cavity while the 2 patients with absence of uptake showed diffusely infiltrating tumors in the wide area of the choroid with or without a small mushroom-like protrusion. One patient with diffuse infiltration showed concurrent liver metastases with high uptake on PET/CT while another patient with a nodular tumor developed liver metastases a year later. The tumors with higher SUVmax had a tendency to have a wider area and greater thickness on pathological sections (rho = 0.775, P = 0.0557, Spearman rank correlation test).
FDG-PET/CT showed correlation of the uptake with tumor sizes but was limited in detecting diffusely infiltrating tumors in the choroid without nodular formation.

DOI： 10.1007/s10147-013-0538-5

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DOI： 10.11392/jsao.43.189

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DOI： 10.3960/jslrt.54.143

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Language：English   Publisher：Informa Healthcare  

Background: The examination of depth perception with three-rods test, in addition to visual acuity testing, is required to obtain motor vehicle license to drive taxies and trucks, according to the Road Traffic Act in Japan. The aim of this study was to examine whether the results of the three-rods test would correlate with the results of static stereopsis tests, used in ophthalmic practice. Methods: This study involved 54 normal subjects, 9 women and 45 men, with ages ranging from 18 to 25 (mean, 20.8) years. All had visual acuity of 0.8 or better with or without glasses or contact lenses correction and had no strabismus at the distant (5m) or near (0.3m) fixation. TNO Stereotest and Titmus Stereotest were examined at 40cm while Distance Randot Stereotest was at 3m. At three-rods test, a central rod was moved at the speed of 50mm/sec forward and backward automatically against two laterally located fixed rods, placed inside the illuminated box. An examinee at the distance of 2.5m observed the rods inside the box from a small viewing window and pushed a button to stop the central rod in alignment with the fixed rods. Erred distance (mm) of the central rod from the fixed rods as a mean of 4 measurements was correlated with stereoacuity in second of arc, measured by three kinds of the stereopsis tests. Results: The erred distance of three-rods test was positively correlated with static stereoacuity at distance measured with Distance Randot Stereotest (ρ=0.418, p=0.0023, Spearman rank correlation test) and also with the other stereopsis tests at near fixation. The stereoacuity at near fixation, measured by TNO Stereotest and Titmus Stereotest, was positively correlated with each other (ρ=0.431, p=0.0017). Conclusion: Three-rods test, examining depth perception, together with the response by eye-hand coordination, gave consistent results with distant static stereoacuity when measured with Distance Randot Stereotest. © 2014 Informa Healthcare USA, Inc.

DOI： 10.3109/09273972.2014.939766

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We have developed a photoelectric dye-coupled polyethylene film as a prototype of retinal prosthesis, which we named Okayama University-type retinal prosthesis. The purposes of this study are to conduct behavior tests to assess vision in Royal College of Surgeons (RCS) rats that underwent subretinal implantation of the dye-coupled film and to reveal retinal response to the dye-coupled film by immunohistochemistry. Polyethylene films were made of polyethylene powder at refined purity, and photoelectric dyes were coupled to the film surface at higher density compared with the prototype. Either dye-coupled film or dye-uncoupled plain film used as a control was implanted subretinally from a scleral incision in both eyes of an RCS rat at 6 weeks of the age. Behavior tests 2, 4, 6, and 8 weeks after implantation were conducted by observing head turning or body turning in the direction consistent with clockwise or counterclockwise rotation of a black-and-white-striped drum around a transparent cage housed with the rat. After the behavior tests at 8 weeks, rats' eyes were enucleated to confirm subretinal implantation of the films and processed for immunohistochemistry. In the behavior tests, the number of head turnings consistent with the direction of the drum rotation was significantly larger in RCS rats with dye-coupled- compared with plain-film implantation [P &lt; 0.05, repeated-measure analysis of variance (ANOVA), n = 7]. The number of apoptotic neurons was significantly smaller in eyes with dye-coupled- compared with plain-film implantation (P &lt; 0.05, Mann-Whitney U test, n = 6). In conclusion, subretinal implantation of photoelectric dye-coupled films restored vision in RCS rats and prevented the remaining retinal neurons from apoptosis.

DOI： 10.1007/s10047-013-0697-1

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To test the effect of double vision on postural stability, we measured postural stability by electric stabilometry before prism-wearing and immediately, 15, 30, and 60min after continuous prism-wearing with 6 prism diopters in total (a 3-prism-diopter prism placed with the base up in front of one eye and with the base down in front of the other eye) in 20 normal adult individuals with their eyes open or closed. Changes in stabilometric parameters in the time course of 60min were analyzed statistically by repeated-measure analysis of variance. When subjects' eyes were closed, the total linear length (cm) and the unit-time length (cm/sec) of the sway path were significantly shortened during the 60-minute prism-wearing (/0.05). No significant change was noted in any stabilometric parameters obtained with the eyes open during the time course. In conclusion, postural stability did not change with the eyes open in the condition of large vertical diplopia, induced by prism-wearing for 60min, while the stability became better when measured with the eyes closed. A postural control mechanism other than that derived from visual input might be reinforced under abnormal visual input such as non-f usionable diplopia.

DOI： 10.18926/AMO/50411

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The purpose of this study was to develop a series of stereoscopic anatomical images of the eye and orbit for use in the curricula of medical schools and residency programs in ophthalmology and other specialties. Layer-by-layer dissection of the eyelid, eyeball, and orbit of a cadaver was performed by an ophthalmologist. A stereoscopic camera system was used to capture a series of anatomical views that were scanned in a panoramic three-dimensional manner around the center of the lid fissure. The images could be rotated 360 degrees in the frontal plane and the angle of views could be tilted up to 90 degrees along the anteroposterior axis perpendicular to the frontal plane around the 360 degrees. The skin, orbicularis oculi muscle, and upper and lower tarsus were sequentially observed. The upper and lower eyelids were removed to expose the bulbar conjunctiva and to insert three 25-gauge trocars for vitrectomy at the location of the pars plana. The cornea was cut at the limbus, and the lens with mature cataract was dislocated. The sclera was cut to observe the trocars from inside the eyeball. The sclera was further cut to visualize the superior oblique muscle with the trochlea and the inferior oblique muscle. The eyeball was dissected completely to observe the optic nerve and the ophthalmic artery. The thin bones of the medial and inferior orbital wall were cracked with a forceps to expose the ethmoid and maxillary sinus, respectively. In conclusion, the serial dissection images visualized aspects of the local anatomy specific to various procedures, including the levator muscle and tarsus for blepharoptosis surgery, 25-gauge trocars as viewed from inside the eye globe for vitrectomy, the oblique muscles for strabismus surgery, and the thin medial and inferior orbital bony walls for orbital bone fractures. © 2013 by Okayama University Medical School.

DOI： 10.18926/AMO/49666

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

Acute retinal necrosis syndrome (ARNS) is a herpetic infectious eye disease that presents clinicians with difficult decisions to make about the indication and timing of surgical intervention. Here I report 2 patients who underwent prophylactic and early vitrectomy with good visual outcomes. Case 1, a 72-year-old man, had a second recurrence of ARNS in the left eye in 2011 and underwent early vitrectomy in the acute inflammatory phase to remove previously formed vitreous opacity and vitreoretinal adhesions, in parallel with intravenous acyclovir and oral prednisolone administration. He had experienced ARNS in the right eye in 1983, in the left eye in 1986, and a recurrence in the left eye in 1999. Case 2, a 66-year-old woman, developed ARNS in the right eye. All of the circumferential retinal lesions became degenerative with intravenous acyclovir and prednisolone. She underwent a vitrectomy in the post-inflammatory phase, since epiretinal proliferation was noted through vitreous opacity with complete posterior vitreous detachment. These cases suggest that early vitrectomy in the acute inflammatory phase would be indicated for pre-existing vitreoretinal adhesions, while prophylactic vitrectomy in the post-inflammatory phase would be indicated for epiretinal proliferation.

DOI： 10.18926/AMO/49046

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Four consecutive patients presented with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the conjunctiva. After the initial resection, long-term follow-up without additional therapy showed the clinical relapse. Fluorodeoxyglucose positron emission tomography fused with computed tomography (PET/CT) showed abnormal uptake in the conjunctival relapsed lesions, which were, on reresection, again proven as MALT lymphoma. Small and thin lesions of MALT lymphoma in the conjunctiva can be detected by fluorodeoxyglucose PET/CT. The resolution of PET/CT, delineated in this study, could be applied to the other areas of the body to achieve more accurate staging of lymphoma.

DOI： 10.1097/RLU.0b013e31823ea96d

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Language：English   Publisher：ELSEVIER SCIENCE INC  

Purpose: To describe the clinical and cytopathologic characteristics in patients with vitreous opacity of unknown cause or preceding inflammation, diagnosed cytopathologically as inflammation.
Design: Retrospective case series.
Participants: Forty-three consecutive patients (61 eyes) who underwent vitrectomy for vitreous opacity of unknown cause or preceding inflammation and were diagnosed cytopathologically with inflammation at one institution in 6 years from 2005 to 2010. During the same period, 11 consecutive patients with vitreous opacity of unknown cause were diagnosed cytopathologically with lymphoma (large B-cell lymphoma) and were excluded from the study.
Methods: Cell blocks were made by centrifugation of vitrectomy fluid and embedded in paraffin for immunocytochemistry.
Main Outcome Measures: Cytopathologic and immunocytochemical diagnosis using vitrectomy cell blocks.
Results: Histiocytes (macrophages), small lymphocytes, neutrophils, and eosinophils were predominant cells, with no atypical large cells on hematoxylin-eosin staining. Immunocytochemically, most predominant cells were CD68-positive histiocytes (macrophages), followed by CD3-positive T cells, but CD20- or CD79a-positive B cells were rarely present. Epithelioid cells, positive for CD68, were found in 4 patients with or without an established diagnosis of sarcoidosis, and giant multinucleated cells were found in 2 patients with suspected preceding self-limiting Vogt-Koyanagi-Harada disease, based on the presence of depigmented red fundi. Inflammation was diagnosed in 2 patients with vitreous opacity who had a preceding onset of brain lymphoma or systemic lymphoma.
Conclusions: The presence of macrophages, combined with small T lymphocytes, was a major sign in intravitreal inflammation, manifesting as vitreous opacity. A simple technique of cytopathology and immunocytochemistry, using vitrectomy cell blocks, can be performed in most pathology laboratories.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:827-837 (C) 2012 by the American Academy of Ophthalmology.

DOI： 10.1016/j.ophtha.2011.10.020

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Language：English   Publisher：NATURE PUBLISHING GROUP  

Idiopathic superior oblique muscle palsy presents, as quantitative phenotypes, vertical deviation and cyclodeviation in eye alignment on clinical testing, and superior oblique muscle hypoplasia on imaging. We determined ARIX and PHOX2B polymorphisms as genotypes, and analyzed phenotype-phenotype and genotype-phenotype correlations in 37 patients with idiopathic superior oblique muscle palsy. Vertical deviations were measured at upright position of the head and head tilt for 30 degrees to either side, and angles of objective excyclodeviations were determined by image analysis on fundus photographs. Cross-sectional areas of the superior oblique muscle near the eye globe-optic nerve junction were measured by image analysis on coronal sections of magnetic resonance imaging to calculate the paretic-side/normal-side ratios. Among the phenotypes, the increase in vertical deviations elicited by head tilt to the paretic side, the decrease in vertical deviations elicited by head tilt to the normal side and the difference of angles of objective excyclodeviations between the paretic side and normal side were significantly correlated inversely with the paretic-side/normal-side ratios of the cross-sectional areas of the muscle (r=-0.43 with P=0.0084, r=-0.34 with P=-0.038, and r=-0.43 with P=0.009, respectively, n=37, Pearson's correlation test). Fifteen patients with ARIX and/or PHOX2B polymorphisms had significantly greater paretic-side/normal-side ratios of the muscle compared with 20 patients without the polymorphisms (P=0.017, n=35, Mann-Whitney U-test). The patients with ARIX and/or PHOX2B polymorphisms had less hypoplastic superior oblique muscles. Journal of Human Genetics (2012) 57, 122-129; doi: 10.1038/jhg. 2011.138; published online 15 December 2011

DOI： 10.1038/jhg.2011.138

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Language：English   Publisher：The Japanese Society for Lymphoreticular Tissue Research  

In February 2002, a 42-year-old woman developed ocular adnexal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), MALT lymphoma, in the bilateral orbits involving lacrimal glands. She underwent 30 Gy external beam irradiation to the orbital lesions on both sides. She was well until November 2008 when she developed abdominal lymphadenopathy and transabdominal excisional biopsy showed mixed cellularity classical Hodgkin lymphoma at stage II. She underwent standard combination chemotherapy. In July 2010, she developed systemic lymphadenopathy and was diagnosed with diffuse large B-cell lymphoma (DLBCL) by cervical lymph node biopsy. She underwent rituximab monotherapy and finally allogeneic hematopoietic stem cell transplantation in October 2010, but died of renal failure in February 2011. Amplification by polymerase chain reaction of the immunoglobulin heavy chain gene gave rise to dominant discrete fragments of the same size between the orbital lesion with MALT lymphoma in 2002 and the cervical lymph node lesion with DLBCL in 2010. The sequential development of MALT lymphoma, Hodgkin lymphoma, and DLBCL in the long-term course of this patient suggests the common origin of the neoplastic cells, changing their pathological faces in response to irradiation and combination chemotherapy. [J Clin Exp Hematopathol 52(1) : 41-49, 2012]

DOI： 10.3960/jslrt.52.41

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Language：English   Publisher：SPRINGER TOKYO  

DOI： 10.1007/s10047-011-0597-1

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

An 18-year-old woman with a 2-year history of hypertension and headache was diagnosed with noradrenal in-secreting bilateral adrenal pheochromocytomas with paragangliomas in the background of von Hippel-Lindau disease with family histories and a missense mutation, 712C to T (Arg167Trp) in the VHL gene. She had optic disc hemangioma in the left eye which gradually enlarged and caused serous retinal detachment on the macula in one year. Low-dose external beam radiation (20 Gy) was adminisitered to the left eye using a lens-sparing single lateral technique. She underwent craniotomy for cerebellar hemangioblastoma at the age of 22 years and total pancreatectomy for multiple neuroendocrine tumors at the age of 24 years. In the 6-year follow-up period after the radiotherapy, the optic disc hemangioma gradually reduced in size and its activity remained low, allowing good central vision to be maintained. External beam radiation is recommended as a treatment option for the initial therapy for optic disc hemangioma.

DOI： 10.18926/AMO/45273

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Language：English   Publisher：TAYLOR & FRANCIS INC  

Purpose: To report a retinal vasoproliferative granulomatous lesion in association with pyoderma.
Design: Single case report.
Methods: A 32-year-old woman had blurred central vision in the right eye, concurrent with pyoderma of the fingers of both hands, 2 days later followed by fever.
Results: The patient had a granulomatous lesion in the upper retina, which caused leakage, leading to subretinal and intraretinal accumulation of hard exudates in the posterior pole, together with periphlebitis extending over the wider area of the retina. The culture of the pyodermic lesion detected Streptococcus pyogenes. With the 2-month course of amoxicillin-clavulanate, combined with prednisolone tapered from 30 mg daily, the visual acuity (decimal fraction) in the right eye returned from 0.01 (logMAR = 2) to 0.9 (logMAR = 0.1). However, after the discontinuation of the antibiotics and prednisolone, the retinal lesion became more vasoproliferative and caused leakage to reduce the vision again. The leakage was remedied by laser photocoagulation to the retinal lesion.
Conclusions: The retinal granulomatous lesion was caused by streptococcal infection in pyoderma and later became more vasoproliferative with macroaneurysms and microaneurysms even after the initial subsidence of the lesion with antibiotics treatment.

DOI： 10.3109/09273948.2010.509531

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Trehalose, a non-reducing disaccharide, is known as an exceptional protector against desiccation and heat stress. Differential scanning calorimetry is a simple tool to determine thermodynamic parameters concerning the structural state of proteins. In this study, we measured denaturation temperature (or melting temperature) of dried lenses to know the effect of trehalose pretreatment. Isolated porcine lenses were incubated in wells without any solution or with saline, 100 mM trehalose, or 100 mM cyclic tetrasaccharide in saline at room temperature for 150 min. The solutions were removed, and all lens samples were dried at room temperature and in room humidity until the weight showed no change. The nucleus of each sample was taken out and placed on a measuring platform for differential scanning calorimetry. The denaturation temperature of the dried lenses significantly rose by about 10 degrees C with 100 mM trehalose pretreatment, compared to no pretreatment, pretreatment with saline or 100 mM cyclic tetrasaccharide (P &lt; 0.05, analysis of variance, P &lt; 0.05, Student-Newman-Keuls tests, n = 7). The denaturation temperature showed no difference among the dried lenses with no pretreatment or pretreatment by saline or cyclic tetrasaccharide. In conclusion, pretreatment with trehalose raises denaturation temperature of the dried porcine lens. Trehalose might stabilize the dried tissue structure to get a higher denaturation temperature.

DOI： 10.1007/s10973-010-0906-6

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Language：English   Publisher：The Japanese Society for Lymphoreticular Tissue Research  

In 2000, a 48-year-old woman developed a left orbital mass with lacrimal gland involvement and then, in 2003, a right orbital mass with lacrimal gland involvement, both of which were diagnosed as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). She underwent 30 Gy external beam radiation to bilateral orbital lesions. The lymphoma cells in both lesions did not share the same clonality, as shown by amplification by polymerase chain reaction of the immunoglobulin heavy chain gene. Immunoglobulin light chain analysis by immunohistochemistry and messenger RNA in situ hybridization showed λ chain monotype in the left orbital lesion but κ chain monotype in the right orbital lesion. She developed recurrent left orbital mass with high uptake on fluorodeoxyglucose positron emission tomography fused with computed tomography in 2010, and excisional biopsy disclosed the formation of follicles and infiltration with immunoglobulin G4 (IgG4)-positive plasma cells mainly in interfollicular areas. The immunoglobulin light chain analysis showed the λ chain and κ chain bitype. With the immunohistopathological diagnosis of IgG4-related disease, the serum IgG4 level was found to show elevation at 376 mg/dL, and the patient chose observation. This is the first reported case of development of IgG4-related disease after bilataral orbital MALT lymphoma with external beam radiotherapy. [J Clin Exp Hematopathol 51(2) : 125-133, 2011]

DOI： 10.3960/jslrt.51.125

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Language：English   Publisher：The Japanese Society for Lymphoreticular Tissue Research  

The purpose of this study is to determine the relationship of ocular adnexal benign or reactive lymphoid hyperplasia, including orbital pseudotumor, with immunoglobulin G4 (IgG4)-related diseases. Medical charts of 9 consecutive patients with ocular adnexal benign lymphoid lesions, seen in the Department of Ophthalmology, Okayama University Hospital, were reviewed, and pathological sections were restained immunohistochemically for IgG4-, IgG-, and CD138-positive plasma cells. The diagnosis of IgG4-positive lesions was based on 10 or more IgG4-positive plasma cells in a high-power field and greater than 40% ratios of IgG4-positive plasma cells/CD138-positive plasma cells and IgG4-positive plasma cells/IgG-positive plasma cells. IgG4-positive lesions were determined as absent in 5 patients (4 with bilateral lacrimal/orbital lesions and one with a unilateral conjunctival lesion), none of whom showed systemic manifestations. In contrast, IgG4-positive lesions were present in 4 patients (3 with bilateral lacrimal/orbital lesions and one with a unilateral lacrimal/orbital lesion), who showed systemic manifestations : one with Hashimoto thyroiditis, one with IgG4-positive bilateral interstitial lung disease and hepatic inflammatory pseudotumor, one with bilateral interstitial lung disease, and one with systemic lymphadenopathy and antiphospholipid syndrome. In conclusion, IgG4-positive ocular adnexal benign lymphoid lesions might be used as a benchmark for the probable presence of other systemic lymphoid lesions.

DOI： 10.3960/jslrt.50.129

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Other Link： http://search.jamas.or.jp/link/ui/2011254628

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The purpose of this study is to report on a patient who developed conjunctival lesions of blastic plasmacytoid dendritic cell neoplasm (BPDCN) after radiation to skin lesions of the same pathological type. A 79-year-old man developed salmon-pink lesions in the lower fornix of the conjunctiva of both eyes and biopsy revealed BPDCN. One and a half years previously, he noticed an erythematous plaque with a 30-mm diameter, which later became multiple, on the left chest, and the biopsy revealed BPDCN. The bone marrow was negative for CD56-positive cells, but fluorescence-activated cell sorting analysis of peripheral blood cells revealed a group of cells positive for CD4 and CD56, or CD4 and CD123. The monocyte fraction, in an increased percentage of white blood cell counts, did contain atypical cells positive for the three markers. Whole-body 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography demonstrated no abnormal uptake lesions. He received 30 Gy of radiation to the chest lesions, and later, the same dose of radiation to novel skin lesions on the back, waist, and chest, and also to pharyngeal lesions. In conclusion, the conjunctiva could be involved with BPDCN and pathological differential diagnosis by biopsy is mandatory to establish the correct diagnosis.

DOI： 10.3960/jslrt.51.49

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Language：English   Publisher：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. Computerized static stabilometry is a clinical test in neurologic and muscular diseases to assess postural stability or body sway in a quantitative manner. The purpose of this study was to examine whether postural stability would change in the process of the prism adaptation test in patients with intermittent and constant exotropia.
METHODS. Postural stability was measured before the prism adaptation test and immediately, 15 minutes, and 60 minutes after the prism adaptation test by computerized static stabilometry in 17 consecutive adult patients with exotropia, including 10 patients with intermittent exotropia and seven with constant exotropia. Stabilometric parameters were compared between patients with intermittent and those with constant exotropia for 60 minutes by repeated-measures analysis of variance as statistical analysis.
RESULTS. The Romberg quotients for the root mean square areas of the sway path (cm(2)), the area in the condition of the patients&apos; eyes open, divided by that in the condition of the patients&apos; eyes closed, increased significantly in the time course of the prism adaptation test and returned to the pretest level in patients with intermittent exotropia and in patients with constant exotropia (P = 0.0173). No significant difference in the Romberg quotients was noted between the patients with intermittent exotropia and those with constant exotropia.
CONCLUSIONS. Postural instability became more pronounced by the prism adaptation test in the patients with exotropia. Binocular visual and motor perceptional changes induced by the prism adaptation test could lead to postural instability, with adaptation taking place 60 minutes after the start of the test. (Invest Ophthalmol Vis Sci. 2010;51:6341-6347) DOI:10.1167/iovs.105840

DOI： 10.1167/iovs.10-5840

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Purpose: To report a patient who showed neuroendocrine tumor (carcinoid) metastasis to the medial rectus muscle and to review patients' characteristics of carcinoid metastases to the extraocular muscles. Case: A 72-year-old woman, who initially presented with spindle-shaped enlargement of the right medial rectus muscle, was followed for 3 years with a diagnosis of orbital myositis. Initial biopsy of the medial rectus muscle showed inflammation only. She showed remission and exacerbation of right proptosis and eyelid swelling, which responded to oral and intravenous steroids. On the occasion of abdominal computed tomography for ischemic colitis, a large retroperitoneal mass was detected and diagnosed as well-differentiated neuroendocrine tumor. The gradual increase of the medial rectus muscle with optic nerve compression, and hence, visual reduction, prompted a second excisional biopsy of the medial rectus mass, which proved to be neuroendocrine tumor metastasis. Whole body 2-[ 18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography fused with computed tomography revealed abnormal uptake only in the right orbit (maximum standardized uptake value: SUVmax3.83), and the patient underwent radiation to the right orbit with the subsidence of the residual mass. Results: The literature review found 15 patients, including this patient, with neuroendocrine tumor metastases to the extraocular muscles. Frequent symptoms and signs were diplopia, proptosis, and ocular motility limitation. Conclusions: Neuroendocrine tumor appears to have propensity to extraocular muscle metastases and its slow growth might pose difficulty in differential diagnoses of orbital myositis. © 2010 Informa Healthcare USA, Inc.

DOI： 10.3109/09273972.2010.525779

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Language：English   Publisher：SPRINGER  

General electronic medical records systems remain insufficient for ophthalmology outpatient clinics from the viewpoint of dealing with many ophthalmic examinations and images in a large number of patients. Filing systems for documents and images by Yahgee Document View (Yahgee, Inc.) were introduced on the platform of general electronic medical records system (Fujitsu, Inc.). Outpatients flow management system and electronic medical records system for ophthalmology were constructed. All images from ophthalmic appliances were transported to Yahgee Image by the MaxFile gateway system (P4 Medic, Inc.). The flow of outpatients going through examinations such as visual acuity testing were monitored by the list "Ophthalmology Outpatients List" by Yahgee Workflow in addition to the list "Patients Reception List" by Fujitsu. Patients&apos; identification number was scanned with bar code readers attached to ophthalmic appliances. Dual monitors were placed in doctors&apos; rooms to show Fujitsu Medical Records on the left-hand monitor and ophthalmic charts of Yahgee Document on the right-hand monitor. The data of manually-inputted visual acuity, automatically-exported autorefractometry and non-contact tonometry on a new template, MaxFile ED, were again automatically transported to designated boxes on ophthalmic charts of Yahgee Document. Images such as fundus photographs, fluorescein angiograms, optical coherence tomographic and ultrasound scans were viewed by Yahgee Image, and were copy-and-pasted to assigned boxes on the ophthalmic charts. Ordering such as appointments, drug prescription, fees and diagnoses input, central laboratory tests, surgical theater and ward room reservations were placed by functions of the Fujitsu electronic medical records system. The combination of the Fujitsu electronic medical records and Yahgee Document View systems enabled the University Hospital to examine the same number of outpatients as prior to the implementation of the computerized filing system.

DOI： 10.1007/s10916-009-9303-8

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Language：English   Publisher：WICHTIG EDITORE  

PURPOSE. To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs).
METHODS. In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively.
RESULTS. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively.
CONCLUSIONS. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally. (Eur J Ophthalmol 2010; 20: 454-6)

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Language：English   Publisher：ELSEVIER SCIENCE INC  

PURPOSE: To search for a new definition of muscle hypoplasia in congenital or idiopathic superior oblique muscle palsy.
DESIGN: Retrospective case-control study.
METHODS: Cross-sectional areas of the superior oblique and 4 rectus muscles near the eye globe-optic nerve junction were measured by an image analysis software on magnetic resonance images of 50 patients with congenital or idiopathic superior oblique muscle palsy and 45 patients with other disease conditions serving as a control. The paretic side/contralateral normal side ratios of the cross-sectional areas and the left side/right side ratios were calculated for the superior oblique muscle palsy patients and the control patients, respectively.
RESULTS: The 95% confidence intervals in paretic side/contralateral side ratios of cross-sectional areas of the superior oblique muscle were 0.55 to 0.80 in the right-side superior oblique muscle palsy, and 0.48 to 0.75 in the left-side palsy, while the 95% confidence interval in the left side/right side ratios was 0.99 to 1.00 in the control. The 95% confidence intervals in the left side/right side ratios of the 4 rectus muscles were 1.00, both in the superior oblique muscle palsy and in the control.
CONCLUSIONS: The muscle hypoplasia could be defined as such when the paretic side/contralateral side ratios of cross-sectional areas of the superior oblique muscle on magnetic resonance images fell outside the 95% confidence interval of the ratios in normal controls. (Am J Ophthalmol 2010;149:508-512. (C) 2010 by Elsevier Inc. All rights reserved.)

DOI： 10.1016/j.ajo.2009.09.022

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Language：English   Publisher：The Japanese Society for Lymphoreticular Tissue Research  

The purpose of this study is to determine the same or different clonality between bilateral or recurrent lesions, or between or among ocular adnexal lesions and systemically multifocal lesions in 10 consecutive patients with ocular adnexal lymphoma : 8 had extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) and 2 had mantle cell lymphoma, observed from 1995 to 2008 at Okayama University Hospital. A discrete DNA fragment was generated by polymerase chain reaction amplification of the immunoglobulin heavy chain gene from all samples except for two samples of bilateral orbital mantle cell lymphoma lesions and one sample of the scalp skin MALT lymphoma lesion. The size of DNA fragments were the same between bilateral orbital or conjunctival lesions of 5 patients, between original and recurrent conjunctival lesions of one patient, between the orbital lesion and the oral cavity lesion in one patient, and among bilateral orbital lesions, buccal, rectum, and stomach lesions of one patient. Sequencing of the DNA fragments showed the same sequence between bilateral or recurrent or multifocal lesions in 8 patients except for one : the bilateral orbital lesions, rectum, and stomach lesions shared the same sequence while the buccal lesion had one nucleotide difference compared to the sequence shared by the other 4 lesions. In conclusion, bilateral, recurrent, or systemically multifocal lesions of ocular adnexal lymphoma shared the clonality between or among the lesions. [J Clin Exp Hematopathol 50(1) : 27-38, 2010]

DOI： 10.3960/jslrt.50.27

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Language：English   Publishing type：Book review, literature introduction, etc.   Publisher：SPRINGER TOKYO  

Patients with retinitis pigmentosa lose photoreceptor cells as a result of genetic abnormalities and hence become blind. Neurons such as bipolar cells and ganglion cells remain alive even in the retina of these patients, and ganglion cells send axons to the brain as the optic nerve. The basic concept of retinal prostheses is to replace dead photoreceptor cells with artificial devices to stimulate the remaining neurons with electric currents or potentials. Photodiode arrays and digital camera-type electrode arrays are the two main approaches for retinal prostheses to stimulate retinal neurons, but these arrays have the problems of poor biocompatibility, low sensitivity, and low output of electric currents, and hence have a requirement for external electric sources (batteries). To overcome these problems, we are developing photoelectric dye-based retinal prostheses that absorb light and convert photon energy to generate electric potentials. The prototype, using a photoelectric dye-coupled polyethylene film, could induce intracellular calcium elevation in photoreceptor-lacking embryonic retinal tissues and cultured retinal neurons. The subretinal implantation of the prototype in the eyes of Royal College of Surgeons (RCS) rats led to vision recovery as proved by a behavior test. The photoelectric dye that was chosen for the prototype did not exhibit any cytotoxicity. The surface potentials of the photoelectric dye-coupled film showed a rapid on-and-off response to illumination with a threshold for light intensity as measured by a Kelvin probe system. Photoelectric dye-based retinal prostheses are thin and soft, and therefore, a sheet of the film of large size, corresponding to a large visual field, could be inserted into the vitreous and then to the subretinal space through a small opening by rolling up the film. Clinical studies of photoelectric dye-based retinal prostheses in patients with retinitis pigmentosa who lose sight will be planned after the manufacturing control and the quality control had been established for the medical device.

DOI： 10.1007/s10047-009-0471-6

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

The vision-screening program for 3.5-year-old children in Japan consists of 3 steps: questionnaires and home visual acuity testing, visual acuity testing by nurses and inspection by medical officers at regional Public Health Centers, and examinations by ophthalmologists. In this study, we tested refraction with a hand-held autorefractometer in addition to visual acuity testing and inspection to reveal whether or not autorefraction leads to better detection of eye problems. Autorefraction was performed in 6 consecutive sessions by a single examiner in 265 children at 3.5 years of age who all visited the same center. The children were sent to the third step of examinations by ophthalmologists based on refractive error criteria: &gt; 3 diopters myopia or &gt; 1 diopter hyperopia, and/or &gt; 2 diopters astigmatism in either eye, in addition to the current criteria: 1) failure in either eye for 0.5 visual acuity at the center, 2) eye-related symptoms revealed by the questionnaires, or 3) eye problems detected by medical officers. Notices to visit ophthalmologists were issued for 64 children (24%), and 37 of those (58%) made the visits, so that documents containing final diagnoses were sent back to the Public Health Office. Of the 64 children, 12 were sent to ophthalmologists based on the current criteria only, 10 based on both the current criteria and the refractive error criteria, and 42 based on the refractive error criteria only. Twelve of the 13 children visiting ophthalmologists by the current criteria had diagnoses such as amblyopia and strabismus. In contrast, 15 of 24 children visiting ophthalmologists by only the refractive error criteria had mainly diagnoses of refractive errors, with no serious problems. In conclusion, autorefraction in addition to visual acuity testing and inspection led to detection of only one additional case of an eye disease at 3.5 years, while tripling the number of children sending to the third-step examination by an ophthalmologist. Thus, from a cost-effectiveness standpoint, autorefraction is not recommended as an additional test when the current system is conducted as designed.

DOI： 10.18926/AMO/31819

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Language：English   Publisher：MOLECULAR VISION  

Purpose: Comitant strabismus is a common pediatric ophthalmic disorder with both genetic and non-genetic factors contributing to its etiology. The aim of the current study is to investigate the phenomenon of a parent-of-origin effect, genomic imprinting, as a possible mode of inheritance in comitant strabismus.
Methods: We performed parametric genome-wide MOD score (model-maximizedLOD score) linkage analysis, incorporating imprinting effects, for 382 microsatellite markers in a sample of 258 individuals (117 males and 141 females) from 55 Japanese families with comitant strabismus. We included individuals as affected patients if they presented with comitant esotropia or exotropia based on ophthalmic examination, history taking, or analysis of medical records.
Results: Significant or suggestive linkage to comitant strabismus with evidence of maternal or paternal imprinting was detected at D4S1575 (4q28.3), D7S486 (7q31.2), D11S1320 (11q24.2), D12S324 (12q24.32), and D19S420 (19q13.11). Using the MOD score approach, we found new evidence of linkage to comitant strabismus at three loci on chromosomes 6q26 (MOD(imp)=MOD(reg)=3.75), 12q24.32 (MOD(imp)=3.36), and 19q13.11 (MOD(imp)=3.79).
Conclusions: The results suggest that the parent-of-origin effect may play a role in the etiology of comitant strabismus.

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Purpose: To describe clinical features of inferior rectus muscle aplasia in Japanese patients and to gain insight into its pathogenesis. Methods: Case presentation and literature review of 16 Japanese patients with inferior rectus muscle aplasia. Results: The age at presentation of 16 patients (9 females, 4 males, and 3 with unknown gender) varied from 7 months to 73 years (mean, 21.8 years). The inferior rectus muscle was absent on the right side in 10 patients, on the left side in 4 patients, and on both sides in 2 patients. Structural anomalies of the eye globe, such as microphthalmos, microcornea, and coloboma of varying degrees, were present on the ipsilateral side of the inferior rectus muscle aplasia in 4 patients and on the contralateral side in 1 patient. As surgical findings, anomalous inferiorly located insertion of the medial rectus muscle was discovered in 5 patients: 1 patient in association with microcornea and iris coloboma. Frequent surgical procedures were recession or tenotomy of the superior rectus muscle, combined with downward transposition of the entire or partial tendons of the medial rectus and lateral rectus muscle to the medial and lateral end, respectively, of the putative inferior rectus muscle insertion. Conclusions: The association of coloboma with inferior rectus muscle aplasia suggests that abnormal optic fissure closure during embryogenesis might underlie the muscle aplasia.

DOI： 10.1080/09273970802687504

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The aim of this study is to describe the effect of transarterial embolization from the ophthalmic artery as a pretreatment for orbital exenteration. A 75-year-old Chinese man with a 7-year history of gradual increase of the left eye swelling showed a massive conjunctival tumor growing outwardly from the interpalpebral fissure and had no light perception in the left eye. Magnetic resonance imaging showed orbital invasion of the tumor around the left eyeglobe. The initial surgery for the planned orbital exenteration was discontinued after skin incision around the orbital margin due to massive hemorrhage. The patient underwent transarterial embolization with gelatin sponge (Spongel) of the feeding arteries from the left ophthalmic artery and, the next day, had orbital exenteration with well-controllable bleeding and reconstruction with free vascularized anterolateral thigh cutaneous flap transfer. Pathologically, well-differentiated squamous cell carcinoma proliferated in exophytic, papillary, and nested fashions, arising from the bulbar conjunctiva. Tumor cells were also found in the conjunctival stroma around the vessels. The sclera at the equator had a perforated site with tumor cell invasion, but no intraocular invasion was found. Hematoxylin-positive gelatin sponges were found inside the orbital vessels and large choroidal vessels. In conclusion, transarterial embolization of feeding arteries arising from the ophthalmic artery is a useful pretreatment to control bleeding at orbital exenteration for malignancy.

DOI： 10.1007/s00270-008-9413-6

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The aim of this study is to describe vision loss caused by central retinal artery and posterior ciliary artery occlusion as a consequence of sclerotherapy with a polidocanol injection to a glabellar hemangioma. An 18-year-old man underwent direct injection with a 23-gauge needle of 1 mL of a polidocanol-carbon dioxide emulsion into the glabellar subcutaneous hemangioma under ultrasound visualization of the needle tip by radiologists. He developed lid swelling the next day, and 3 days later at referral, the visual acuity in the left eye was no light perception. Funduscopy revealed central retinal artery occlusion and fluorescein angiography disclosed no perfusion at all in the left fundus, indicating concurrent posterior ciliary artery occlusion. The patient also showed mydriasis, blepharoptosis, and total external ophthalmoplegia on the left side. Magnetic resonance imaging demonstrated the swollen medial rectus muscle. In a month, blepharoptosis and ophthalmoplegia resolved but the visual acuity remained no light perception. Sclerosing therapy for facial hemangioma may develop a severe complication such as permanent visual loss.

DOI： 10.1007/s00270-008-9382-9

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Language：English   Publisher：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. This study was designed to localize chromosomal susceptibility loci for comitant strabismus among Japanese families by genome-wide linkage analyses.
METHODS. Fifty-five Japanese families, with at least two members with comitant strabismus (esotropia and/or exotropia), were subject to full ophthalmic examination, careful ocular history, and review of medical records. DNA was obtained and genotyping was performed with PCR amplification of 400 microsatellite markers. Parametric and nonparametric linkage (NPL) analyses scores were calculated. Linkage analysis was performed for the whole set of families (55 families), and then a second analysis was performed for two subgroups with the phenotypes, esotropia and exotropia.
RESULTS. A multipoint parametric heterogeneity logarithm of the odds (HLOD) score of 3.62 was obtained at marker D4S1575 under a dominant model, with a NPL score of 2.68 (P = 0.001). Testing under different penetrances and disease allele frequencies revealed two other susceptibility loci at 7q31.2 under a recessive model (HLOD scores = 3.93 and 4.40 at 125.2 cM and 107.28 cM, respectively). Analysis of the subgroups revealed new susceptibility loci for esotropia; one locus at 8q24.21 is worthy of further investigation.
CONCLUSIONS. This study suggests multiple susceptibility loci for comitant strabismus. The loci at chromosomes 4q28.3 and 7q31.2 show a significant evidence of linkage. (Invest Ophthalmol Vis Sci. 2009;50:654-661) DOI:10.1167/iovs.08-2437

DOI： 10.1167/iovs.08-2437

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Language：English   Publisher：The Japanese Society for Lymphoreticular Tissue Research  

The purpose of this study is to report the role of whole-body 2-[¹⁸F] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography fused with computed tomography (PET/CT) after immunocytochemical and clonal diagnosis of intraocular lymphoma with vitrectomy cell blocks. Eleven patients with intraocular lymphoma were involved in this study : 6 patients presented with vitreous opacity in both eyes and 5 patients presented with unilateral involvement. The concurrent retinal lesions were present in 6 eyes of 5 patients. Brain lymphoma was diagnosed in 7 of the 11 patients : simultaneous with eye lesions in one patient, following the eye lesions in 3, and prior to the eye lesions in 3. Vitrectomy was done in 17 eyes of the 11 patients, and vitrectomy cell blocks were processed for immunocytochemical staining and clonality analysis by polymerase chain reaction amplification of the immunoglobulin heavy chain gene. The 7 most recent patients were evaluated with fluorodeoxyglucose whole-body PET/CT. Immunocytochemical staining of vitrectomy cell blocks in all patients showed large cells which were positive for CD20 and Ki-67 but negative for CD3, consistent with diffuse large B-cell lymphoma. The size and sequence of amplified fragments of the immunoglobulin heavy chain gene were different between the lesions of both eyes in one patient while they were the same in another patient. PET/CT after the diagnosis by vitrectomy revealed abnormal uptake in the cerebellum of two patients, in the eye as a recurrent lesion of one patient, and in both eyes as residual retinal lesions of one patient. In conclusion, PET/CT could be considered as a method to confirm brain lymphoma or as a reference for initiating additional therapy in the case of eye recurrence or residual lesions after vitrectomy. The clonality of lymphoma cells was variable between the lesions in both eyes. [J Clin Exp Hematopathol 49(2) : 77-87, 2009]

DOI： 10.3960/jslrt.49.77

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DOI： 10.11477/mf.1410102661

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Other Link： http://search.jamas.or.jp/link/ui/2009174898

Language：English   Publisher：SPRINGER TOKYO  

Background: We present the pathological findings at orbital exenteration in a patient with Wyburn-Mason syndrome who underwent transarterial embolization.
Case: A 31-year-old man with a 10-year history of gradual exacerbation of left exophthalmos and left cheek swelling was found to have facial and orbital arteriovenous malformations on the left side. There was no vascular malformation in the brain. The feeding arteries derived from the left internal maxillary artery, facial artery, and ophthalmic artery. He underwent several courses of transarterial embolization of the feeding arteries from the left internal maxillary artery and then from the facial artery, resulting in no reduction of the arteriovenous malformation. He finally elected to undergo ophthalmic artery embolization in the expectation of a reduction and with the understanding that he would lose sight in his left eye. Two years later, he requested lid-sparing orbital exenteration and reconstruction with cutaneous flap transfer and prosthesis for cosmetic reasons.
Observations: Pathologically, orbital vascular channels of varying sizes were filled with embolizing glue and had degenerating vascular wall cells surrounded by inflammatory cell infiltration. The central retinal artery in the optic nerve was also filled with the embolizing glue, and the retina lost the ganglion cell layer and inner nuclear layer but maintained the outer nuclear layer and outer segments.
Conclusions: Marked anastomoses and hence incomplete embolization among the feeding arteries of facial and orbital vascular malformations in Wyburn-Mason syndrome do not respond well to attempts at feeding vessel embolization, which result in unsuccessful closure of the malformation.

DOI： 10.1007/s10384-008-0563-5

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We have designed a new type of retinal prosthesis with a photoelectric dye that transfers photon energy to generate electric potentials. The purpose of this study was to test the safety of a photoelectric dye, 2-[2-[4-(dibutylami no)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide (NK-5962), used for retinal prostheses. The retinal cells, derived from chick neurosensory retinas at the 12-day embryonic stage, were a mixed population of retinal neurons and glial cells, and were cultured for 2 days either under protection from light or under continuous light exposure at 230 lux for 9 h daily in the presence of the photoelectric dye at varying concentrations (1.6 x 10(-5), 1.6 x 10(-6), and 1.6 x 10(-7) M) to assess cell viability by staining live cells and dead cells. Dispersed retinal pigment epithelial cells at the same embryonic stage were incubated with the photoelectric dye at varying concentrations (6.6 x 10(-5), 6.6 x 10(-6), and 6.6 x 10(-)7 M) for 4 h under protection from light or under continuous light exposure at 320 lux to assess cytotoxicity by measuring the activity of lactate dehydrogenase leaking from cells. The majority of retinal cells were alive with only a small percentage of dead cells under the dark condition or the light condition in the presence or the absence of the photoelectric dye. The percentage of dead cells was significantly smaller at higher concentrations of the photoelectric dye (P = 0.0183, two-factor analysis of variance), while the percentage of dead cells was not significantly different between the dark condition and the light condition (P = 0.3102). Percent cytotoxicity values were negative, indicating protective effects in all groups of retinal pigment epithelial cells incubated with varying concentrations of the photoelectric dye. The photoelectric dye showed no cytotoxicity to chick retinal cells or retinal pigment epithelial cells on short-term exposure. In addition, this photoelectric dye might have protective effects on both types of cells.

DOI： 10.1007/s10047-008-0403-x

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：SPRINGER TOKYO  

DOI： 10.1007/s10384-007-0502-x

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We have designed a new type of retinal prosthesis using polyethylene films coupled with photoelectric dye molecules that absorb light and convert photon energy to electric potentials. An extruded-blown film of high-density polyethylene was used as the original polyethylene film. Recrystallized film was made by recrystallization from the melting of the original polyethylene film. A photoelectric dye,2-[2-[4-(dibutylamino)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide, was coupled to the two types of polyethylene films through amide linkages. Samples of the original dye-coupled film, the dye-coupled recrystallized film, and the dye-uncoupled plain film were implanted in the subretinal space of normal adult rats. Frozen sections were cut from the eyes enucleated at 1 week or 1 month and were either stained with hematoxylin and eosin, stained immunohistochemically for glial fibrillary acidic protein (GFAP), or processed for in situ apoptosis detection. The results revealed that retinal tissue damage was negligible with no inflammatory cells and few apoptotic cells. GFAP was significantly up-regulated in retinal sites with the implantation of all types of polyethylene films at 1 week, compared with the adjacent retinal sites (P &lt; 0.005, analysis of variance). The GFAP up-regulation was also present at 1 month for the plain film and dye-coupled recrystallized film (P &lt; 0.05). Glial cell encirclement around the films increased significantly between 1 week and 1 month (P = 0.023, two-factor analysis of variance) but was not significantly different among the three types of polyethylene films (P = 0.4531). These results showed evidence of glial reactions to the photoelectric dye-coupled polyethylene films implanted into the subretinal space of rat eyes and also proved their basic biological safety.

DOI： 10.1007/s10047-007-0398-8

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

We analyzed nucleotide changes in 3 genes, ARIX, PHOX2B, and KIF21A, in 6 patients of 3 families with congenital superior oblique muscle palsy. Three exons of ARIX, 3 exons of PHOX2B, and exons 8, 20, and 21 of KIF21A were amplified by polymerase chain reaction from genomic DNA isolated from the peripheral blood. The DNA fragments were directly sequenced in both directions. In 2 different families, a heterozygous nucleotide change, ARIX 153G &gt; A, in the 5'-untranslated region was found in common between a father and daughter with muscle palsy and between a mother and daughter with muscle palsy (Family No. I and No. 3). In the other family (Family No. 2), a heterozygous 15-nucleotide deletion, PHOX2B 1124del15, resulting in loss of 5 alanine residues in the alanine repeat of the protein, was found in the daughter with muscle palsy and her father with normal traits, but was not found in the mother with muscle palsy. No KIF21A nucleotide change was found in any patients. The ARIX 153G &gt; A polymorphism might be a genetic risk factor for the development of congenital superior oblique muscle palsy.

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DOI： 10.11477/mf.1410102355

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Language：English   Publisher：The Japanese Society for Lymphoreticular Tissue Research  

The purpose of this study is to show that the histopathological type of an orbital lymphoma can differ from the systemic follicular lymphoma that precedes it. A 44-year-old man (Patient #1) and a 50-year-old man (Patient #2) presented with generalized lymphadenopathy due to grade 1 follicular lymphoma proven on lymph node biopsy. Patient #1 was followed without treatment for 16 years when he developed a right orbital mass. Patient #2 underwent several courses of combination chemotherapy as well as radiation but relapsed. The second biopsy of the lymph node nine years later showed the same histopathological type of follicular lymphoma. He developed an orbital mass on the right side 16 years after the initial presentation. In Patient #1, excisional biopsy of the orbital masses showed extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). In Patient #2, biopsy revealed the orbital mass to be T-cell/histiocyte-rich diffuse large B-cell lymphoma. In Patient #1, when comparing the original lymph node biopsy to the orbital biopsy obtained years later, no evidence for clonality was noted by polymerase chain reaction. In Patient #2, the amplification by polymerase chain reaction of the immunoglobulin heavy chain gene rearrangement in the lymph node lesion and the orbital lesion gave rise to a single discrete band with the same DNA sequence except for five nucleotide changes, indicating the same clonality in the presence of genomic changes. In conclusion, orbital lymphomas can occur as a second lymphoma with a different histopathological type in the long-term follow-up of systemic lymphomas. The original and subsequent lymphomatous lesions may or may not share neoplastic cell clonality and all genomics. [J Clin Exp Hematopathol 48(1) : 17-24, 2008]

DOI： 10.3960/jslrt.48.17

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

We previously revealed the prevalence of strabismus and amblyopia in elementary school children between 6 and 12 years of age in Japan in the year 2003. Questionnaires asking the number of children with different types of strabismus and amblyopia were sent to all elementary schools in Okayama Prefecture in the year 2005, and the results in the year 2005 were compared with those obtained in the year 2003. The number of children covered by the return of questionnaires was 84,619 (74%) of 113,763 total pupils, including grades I to 6, in Okayama Prefecture in the year 2005. The total numbers of children with strabismus and amblyopia, including grades I to 6, were 844 (0.99%, 95% confidence interval: 0.94-1.06%) and 173 (0.20%, 95% confidence interval: 0.17-0.23%), respectively. The numbers of children with any type of exotropia and any type of esotropia were 524 (0.62%) and 187 (0.22%), respectively. In the previous survey conducted in 2003, the number of children covered by the return of questionnaires was 86,531 (76%) of 113,254 total pupils. The total numbers of children with strabismus and amblyopia, were 1,112 (1.28%, 95% confidence interval: 1.24-1.36%) and 125 (0.14%, 95% confidence interval: 0.12-0.17%), respectively. The numbers of children with any types of exotropia and esotropia were 602 (0.69%) and 245 (0.28%), respectively. The prevalence of strabismus in this large population of Japanese elementary school children was significantly different between the years 2003 and 2005, while the prevalence of amblyopia was similar between the years.

DOI： 10.18926/AMO/32877

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

We describe herein 2 patients who developed Vogt-Koyanagi-Harada syndrome in the course of renal biopsy-proven immunoglobulin A (IgA) nephropathy. A 61-year-old man with an 11-year history of IgA nephropathy and a 16-year history of thyroiditis, and a 56-year-old man with a 5-year history of IgA nephropathy developed Vogt-Koyanagi-Harada syndrome. At the time of the eye disease presentation, IgA nephropathy was stable without corticosteroids in both patients. Vogt-Koyanagi-Harada syndrome was successfully treated with intravenous administration of prednisolone tapered from 200 mg daily. Vogt-Koyanagi-Harada syndrome is associated with IgA nephropathy, suggesting a similar autoimmune mechanism for both diseases.

DOI： 10.18926/AMO/32898

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Language：English   Publisher：B M J PUBLISHING GROUP  

Background: The remaining retinal neurones or layered structure in the degenerating retina have been the prerequisite for epiretinal or subretinal retinal prostheses.
Aim: To detect the layered structure in the eyes of patients with retinitis pigmentosa by optical coherence tomography.
Methods: In a prospective non- comparative study, 115 eyes of 58 consecutive patients with retinitis pigmentosa underwent optical coherence tomography to obtain horizontal and vertical retinal cross- section images at the centre of the macula. The number of high- reflectance retinal layers, one, two or three layers, was tested to determine whether it correlates with best-corrected visual acuity.
Results: The best- corrected visual acuity was significantly better in the eyes in which more retinal layers were detected ( p &lt; 0.001, Kruskal - Wallis test, p &lt; 0.05, Tukey - Kramer test). The best- corrected visual acuity in the right eye and in the left eye was correlated with each other ( p &lt; 0.001, Spearman rank correlation test) and decreased with age.
Conclusions: Optical coherence tomography can be used to obtain information regarding the retinal layer structure in patients with retinitis pigmentosa, and may be used as a clinical test to assess the feasibility of retinal prostheses in future.

DOI： 10.1136/bjo.2007.114538

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Purpose: To report and summarize eye manifestations of patients with perinuclear pattern antineutrophil cytoplasmic antibody [pANCA, myeloperoxidase (MPO)-ANCA]-associated vasculitis.
Methods: The medical records of four consecutive patients with pANCA (MPO-ANCA) vasculitis who showed eye manifestations were retrospectively reviewed. In addition, the medical literature databases, PubMed and Japana Centra Revuo Medicina for Japanese literature, were searched for pANCA vasculitis patients with eye manifestations.
Results: Three of the four patients treated at the Okayama University Hospital showed unilateral or bilateral scleritis. In the literature review, eight of the 27 patients showed ocular surface manifestations such as scleritis and peripheral keratitis. Other frequent eye presentations were posterior segment manifestations such as central or branch retinal vein occlusion, optic neuropathy, and acute posterior multifocal placoid pigment epitheliopathy (APMPPE). Systemically, the most frequent manifestations were glomerulonephritis in the present patients as well as in the patients reported in the past studies.
Conclusoins: Ocular surface manifestations and posterior segment manifestations were major eye presentations in patients with pANCA-associated vasculitis. ANCA testing including both pANCA and cytoplasmic pattern antineutrophil cytoplasmic antibody would help establish a systemic diagnosis in patients with eye manifestations such as scleritis, retinal vein occlusion, optic neuropathy, or APMPPE.

DOI： 10.1007/s10384-006-0408-z

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

All children at the age of 1.5 and 3 years in Japan undergo physical, mental, and developmental checkups including dental, eye, and hearing examinations. The vision-screening program consists of 3 steps: questionnaires and home visual acuity testing as the first step (only for 3-year-old children), visual acuity testing by nurses and inspection by medical officers at regional Health Centers as the second step, and detailed examinations by ophthalmologists as the third step. This study aims to reveal the prevalence of strabismus and amblyopia as obtained from data in the vision-screening program. The final diagnoses made by ophthalmologists and sent back to the Health Centers in Okayama City were reviewed to elucidate the prevalence of strabismus, amblyopia, refractive errors, and other diseases in 1.5- and 3-year-old children in Okayama City in 5 years from 2000 to 2004. Of approximately 6,500-6,900 total children, 83.7-86.8% at 1.5 years old and 77.8-81.9% at 3 years old were brought to the Health Centers. The rates of strabismus were 0.01-0.12% at 1.5 years old and 0.20-0.34% at 3 years old, while the rates of amblyopia were 0% at 1.5 years old and 0.13-0.18 % at 3 years old. The higher rates of strabismus at 3 years old were attributed mainly to the increase of exotropia and intermittent exotropia. In conclusions, the prevalence of strabismus was different between 1.5- and 3-year-old children. The vision-screening program in Japan functions to detect strabismus and amblyopia.

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DOI： 10.11477/mf.1410101970

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Language：English   Publisher：The Japanese Society for Lymphoreticular Tissue Research  

We report the case of a patient who showed spontaneous regression of bilateral conjunctival extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). A 72-year-old man underwent excisional biopsy for salmon-pink lesions involving the whole circumference of the conjunctiva in the right eye and the lower fornix in the left eye. Histopathology and immunohistochemistry showed MALT lymphoma with immunoglobulin kappa monotype shared by the lesions in both eyes. Because the patient had recurrent pulmonary tuberculosis, radiation initially planned for the large residual lesion in the right eye was postponed. Over two years, including 6 mon with anti-tuberculous treatment, the large lesion in the right eye showed spontaneous regression. The spontaneous regression of conjunctival MALT lymphoma observed in this patient suggests that following excisional biopsy for histopathological diagnosis, observation is a treatment option. [J Clin Exp Hematopathol 47(2) : 79-81, 2007]

DOI： 10.3960/jslrt.47.79

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DOI： 10.11477/mf.1410102014

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Language：English   Publisher：BLACKWELL PUBLISHING  

Photoelectric dyes, which absorb light and convert photon energy to electric potentials, were shown to stimulate retinal neurons in culture. One of these dyes coupled with polyethylene film surface, as a prototype of retinal prostheses, could induce intracellular calcium elevation in chick embryonic retinal tissues. In this study, we used retinal cells from chick embryos in which no photoreceptor outer segments yet developed, and assessed cell adhesiveness and response to the original and modified types of our retinal prostheses. Extruded-blown film of high density polyethylene was used as the original polyethylene film. Polyethylene film surface was modified either by coupling with type 1 collagen or by crystallization from the melt of the original polyethylene film. A photoelectric dye, 2-[2-[4-(dibutylamino)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide, was coupled to these different types of polyethylene films through amide linkage. Retinal cells from chick embryos at the 12-day embryonic stage were cultured on the surface of dye-coupled films. The response of retinal cells to the dye-coupled films was observed by calcium imaging. Cell types, either neurons or glial cells, were detected by immunocytochemical staining and also observed by scanning electron microscopy (SEM). Intracellular calcium elevation was observed in cells, including both neurons and glial cells, on the surface of the original dye-coupled film, collagen-coated dye-coupled film, and dye-coupled recrystallized film, in contrast with no response of cells cultured on the dye-uncoupled plain film. Retinal neurons grew upon colonies of glial cells settling on the surface of all different types of the films. The number of retinal neurons on the collagen-coated dye-coupled film and dye-coupled recrystallized film was significantly larger than the number of neurons on the dye-uncoupled plain film (P = 0.0004, analysis of variance; P &lt; 0.05, Tukey-Kramer test). With SEM, Muller cell-like large cells covered the original dye-coupled film and collagen-coated dye-coupled film, while neuron-like small cells settled directly on the dye-coupled recrystallized film and also formed large colonies on Muller-like cells. Retinal neurons and glial cells were cultured directly on the different types of dye-coupled polyethylene films. Photoelectric dye-coupled polyethylene films could be used as prototypes of retinal prostheses.

DOI： 10.1111/j.1525-1594.2006.00286.x

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

We report herein the disappearance of macular hard exudates after the introduction of hemodialysis in diabetic patients. A 62-year-old woman and a 52-year-old man with diabetes mellitus showed hard exudates in the macula of the left eyes. Both patients had previously undergone panretinal photocoagulation in both eyes. During the follow-up, hemodialysis was introduced for deteriorating chronic renal failure caused by diabetic nephropathy. Half a year later, macular hard exudates in the left eyes disappeared dramatically in both patients, but the visual acuity remained the same. No additional laser treatment was done during the observation period. Hemodialysis is considered to have accelerated the resolution of macular hard exudates in both patients. The deposition of macular hard exudates in diabetic patients is due in part to concurrent poor renal function.

DOI： 10.18926/AMO/30746

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

The purposes of this study were to examine whether body sway is altered immediately after strabismus surgery in children and to find preoperative clinical factors associated with body sway. In a prospective study, body sway was measured on 1-3 days before surgery and on the third day after surgery; for the measurements, computerized static stabilometry was carried out on 28 consecutive patients with strabismus (age range: 3 to 12 years old; mean: 7.4) who underwent strabismus surgery under general anesthesia. The linear length of the sway path (cm), the linear length of the sway path in a particular unit of time (cm/second), and the area of the sway path (cm(2)), indicative of the extent of body sway, all increased significantly among a total of 28 patients in both conditions of the patient's eyes open and closed, as well as among those in a subgroup of 16 patients with exotropia, after they had undergone strabismus surgery (p &lt; 0.05, Wilcoxon signed ranks test). The center of pressure along the Y axis of orientation from the toe to the heel was found to deviate significantly toward the heel postoperatively, as compared with the preoperative center in the subgroup of 16 patients with exotropia (p &lt; 0.05). Before surgery, 15 patients with no stereoacuity exhibited a greater amount of body sway when their eyes were open than did 13 patients with measurable stereoacuity (p &lt; 0.05, Mann-Whitney U-test). In the subgroup of 16 patients with exotropia when their eyes open, 3 patients with abnormal head posture exhibited more extensive body sway than did 13 patients without abnormal head posture (p &lt; 0.05). Body sway was found to significantly increase immediately after strabismus surgery in children with strabismus. Stereoacuity and abnormal head posture are 2 clinical factors associated with preoperative postural instability.

DOI： 10.18926/AMO/30754

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Language：English   Publisher：TAYLOR & FRANCIS INC  

Purpose: To present endophthalmitis-like massive vitreous opacity as a manifestation of cat-scratch disease. Methods: Report of a case. Results: A 47-year-old man developed massive vitreous opacity and total retinal detachment in his right eye after a four-month period of uveitis, which was controlled with oral prednisolone. During the diagnostic vitrectomy, a massive fluffy white opacity adhering to the detached retina was shaved using a vitreous cutter. Further surgical procedures to reattach the retina were not pursued because of the poor state of the infected retina. Pathological examination of the vitreous aspirates revealed pleomorphic bacilli. The serological testing done at referral revealed an IgG titer positive for Bartonella henselae and culture of the vitreous proved the infection a month later. With a mixture of oral sulfamethoxazole (1600 mg daily) and trimethoprim (320 mg daily), the intraocular inflammation subsided. Conclusion: Rapid progression of massive vitreous opacity with total retinal detachment, mimicking endophthalmitis, can occur in cat-scratch disease.

DOI： 10.1080/09273940500545668

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To search for the mechanism of the effect of trehalose on the ocular surface applied as eye drops, we observed trehalose-treated and dried corneal epithelial surfaces of porcine eyes with atomic force microscopy. Full-thickness corneal pieces, 5 × 5 mm in size, were cut out from enucleated porcine eyes. Three kinds of disaccharides, trehalose, maltose, and sucrose, dissolved in saline at 100 mM concentration, and saline as a control, were applied to the epithelial surface of the full-thickness corneal pieces for 1 min. Excess fluid was then absorbed by cotton tips at the epithelial edge of the pieces, and the corneal pieces were dried naturally at room temperature and in room humidity for 72 h. The dried corneal epithelial surfaces were observed first with a dissecting microscope and then fixed on the observation platform for atomic force microscopy. With dissecting microscopy, trehalose-treated corneal epithelial surfaces appeared smoother than saline-, maltose-, or sucrose-treated surfaces. With atomic force microscopy in a tapping mode, saline-, maltose-, and sucrose-treated corneal epithelial surfaces had a larger number of pits in greater sizes than trehalose-treated surfaces. The number of pits measuring 0.14 μm or larger was significantly less in trehalose-treated corneal epithelial surfaces than in saline-treated surfaces (p = 0.0326, analysis of variance [ANOVA], p &lt
0.05, Tukey-Kramer test). No significant difference was found in the number of pits between maltose- or sucrose-treated surfaces and saline-treated surfaces. Mean roughness, an indicator for surface roughness, was significantly lower in trehalose-treated surfaces than in sucrose-treated surfaces (p = 0.0181, ANOVA, p &lt
0.05, Tukey-Kramer test). Trehalose-treated corneal epithelial surfaces are smoother than saline-, maltose-, or sucrose-treated surfaces. One effect of trehalose on the ocular surface is to keep the corneal epithelial surface smooth in drying condition. © Mary Ann Liebert, Inc.

DOI： 10.1089/cpt.2006.4.117

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DOI： 10.4044/joma1947.118.2_131

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Language：Japanese   Publisher：日本工業出版  

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1007/s10384-004-0217-1

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Purpose: To find clinical factors related to the long-term outcome of stereoacuity in Japanese patients with pure accommodative esotropia, including both the refractive type and the nonrefractive type. Methods: The medical charts of 19 Japanese patients (8 boys and 11 girls) with pure accommodative esotropia who were followed for 10 years or more at Okayama University Hospital were reviewed retrospectively. Refractive accommodative esotropia was diagnosed in 8 patients while nonrefractive accommodative esotropia was diagnosed in 11 patients. The patients were divided into two groups, based on a stereoacuity of 120 seconds of arc or better versus 240 seconds of arc or worse as measured by the TNO test at the final visit, and the clinical factors were compared between the two groups. Results: Clinical factors related to a stereoacuity of 240 seconds of arc or worse at the final visit were higher accommodative convergence to accommodation (AC/A) ratios at 6 years of age (p = 0.05), larger residual esodeviations at distance under full correction with glasses at 8 years of age (p = 0.03), and larger residual esodeviations at near at 6 years of age (p = 0.01, Mann-Whitney U-test). Overall, patients with nonrefractive accommodative esotropia tended to show poor levels of stereoacuity at the final visit compared to those with refractive accommodative esotropia (p = 0.059, Fisher exact probability test). Conclusion: This is the first study of the long-term visual outcome in Japanese patients with pure accommodative esotropia including both refractive and nonrefractive types. To obtain better levels of stereoacuity, the residual esodeviations at near and at distance should be kept as small as possible under full correction with glasses, including bifocals, especially at the ages of 6 and 8 years. Copyright © 2005 Taylor &amp
Francis Inc.

DOI： 10.1080/09273970590935084

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

To identify ARIX gene and PHOX2B gene polymorphisms in patients with congenital superior oblique muscle palsy, 3 exons of the ARIX gene and PHOX2B gene were sequenced by genomic DNA amplification with polymerase chain reaction (PCR) and direct sequencing in 31 patients with congenital superior oblique muscle palsy and in 54 normal individuals. A family with a father and one daughter each having congenital superior oblique muscle palsy was also included in this study. Eleven patients with congenital superior oblique muscle palsy had heterozygous nucleotide changes in the ARIX gene, including 4 patients reported on previously. One patient with atrophy of the superior oblique muscle had a new change of T-4G in the promoter region of the ARIX gene. The other 6 patients had a heterozygous nucleotide change of G153A in the 5'-untranslated region (UTR) of the exon 1 of the ARIX gene. These nucleotide changes of the ARIX gene, taken together, had a significant association with congenital superior oblique muscle palsy (P = 0.0022). One patient and 5 patients had heterozygous nucleotide changes of A1106 C and A1121 C in exon 3 of the PHOX2B gene, respectively, while these changes were absent in the normal individuals,. Two patients had both the G153A change in the 5'-UTR of exon 1 of the ARIX gene and the A1121 C change in exon 3 of the PHOX2B gene. In conclusion, the polymorphisms of the ARIX gene and PHOX2B gene may be genetic risk factors for the development of congenital superior oblique muscle palsy.

DOI： 10.18926/AMO/31966

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Purpose: To determine the first presenting signs or symptoms or other reasons leading to the diagnosis of sarcoidosis.
Methods: A retrospective review was made of the records of 123 consecutive Japanese patients with histopathological diagnosis of sarcoidosis seen at a referral-based university hospital.
Results: At the first presentation. eye symptoms in 32 patients. abnormal chest X-ray findings in 52 patients. common cold-like symptoms in 12 patients, lymphadenopathy in 6 patients, skin lesions in 14 patients. and examinations for other diseases in 4 patients led to the final diagnosis. Overall. uveitis was detected in 60 patients (50%) during the follow-up.
Conclusions: Mass screening programs of chest X-rays are the major way sarcoidosis is detected in Japan. Uveitis is seen in about half the patients during the course of sarcoidosis, and eye symptoms are frequent first presentations of sarcoidosis. These facts emphasize the role of ophthalmologists in the diagnosis and management of sarcoidosis.

DOI： 10.1007/s10384-004-0154-z

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Language：English   Publisher：TAYLOR & FRANCIS INC  

Purpose: The aim of this study was to note the clinical features of patients with Behcet's disease who did not show recurrent episodes of eye involvement during long-term follow-up. Methods: A retrospective review was made of 70 Japanese patients with Behcet's disease who were seen during a 23-year period from 1974 to 1996 and followed for five or more years at Okayama University Hospital. The 70 patients were divided into three groups: 36 patients with recurrent episodes of eye involvement; 13 patients with non-recurrent one-time only eye involvement; and 21 patients with no eye involvement at all during a follow-up period of five or more years. Clinical features were compared between these three groups. Results: Female sex (p = 0.0263, chi-square test), young age at the onset (p = 0.0322, Kruskal-Wallis test), and genital ulceration (p = 0.0003, chi-square test) were significantly associated with the non-recurrent or no eye involvement patients. Conclusions: Female patients with onset at a young age and who show the three signs of skin lesions and oral and genital ulcerations may have non-recurrent one-time only or no eye involvement at follow-up. A better visual prognosis can be expected for these patients.

DOI： 10.1080/09273940490518928

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Language：English   Publisher：ELSEVIER SCIENCE BV  

Immune reactions against microorganisms play an important pathogenic role in Adamantiades-Behcet's disease. We had previously obtained Streptococcus sanguinis (strain BD 113-20), isolated from the oral cavity of patients with Adamantiades-Behcet's syndrome. To investigate the pathogenesis of this isolate, we examined neutrophil reactions and levels of cytokine production by lymphocytes after stimulation with the strain. The reactions of neutrophils were examined by chemiluminescence assay using whole blood. The amounts of interferon gamma (IFN-gamma) and interleukin (IL)-4, IL-8, IL-10 and IL-12, produced by peripheral blood mononuclear cells, were measured by ELISA. Strain BD113-20 activated neutrophils from Adamantiades-Behcet's patients and healthy volunteers, and, in addition it increased the IFN-gamma production by lymphocytes. Lymphocytes from Adamantiades-Behcet's patients showed a dominant T helper-1 immune response. Results indicated that both bacterial stimulation and host hypersensitivity might be involved in the symptoms and pathogenesis of Adamantiades-Behcet's disease. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.femsim.2004.07.007

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Background: The purpose of this study is to elucidate the prevalence of strabismus and amblyopia in a large population of Japanese elementary school children, from Grade 1 to Grade 6, ages ranging from 6 to 12 years. The School Health Law requires that all pupils in Grade 1 to Grade 6 be examined for vision and eye problems. Visual acuity testing is done by school teachers and eye disease screening by school ophthalmologists. Pupils with suspected ocular diseases are further examined by extramural ophthalmologists and the results reported back to the schools. The schools then summarize and send uncorrected visual acuity and ocular disease incidence, together with other health statistics, to the municipal education committees. The data are forwarded to the Prefecture Governments and finally submitted to the Education Ministry of the Central Government. Both the Prefecture Governments and the Education Ministry publicize the school health statistics on their websites. The prevalence of strabismus and amblyopia remains unknown from these data because both diagnoses are included under the heading, eye diseases.
Methods: Questionnaires asking about the numbers of children with different types of strabismus and amblyopia were sent to all elementary schools in Okayama Prefecture and the results were summarized.
Results: The number of children covered by the return of questionnaires was 86,531 (76.4%) of 113,254 total pupils in Grade 1 to Grade 6 in Okayama Prefecture in the year 2003. The total numbers of children with strabismus and amblyopia were 1,112 (1.28%) and 125 (0.14%), respectively. The numbers of children with any type of exotropia and any type of esotropia were 602 (0.69%) and 245 (0.28%), respectively. The major types of strabismus and amblyopia were intermittent exotropia in 109 children (0.12%) accommodative esotropia in 19 children (0.02%), anisometropic amblyopia in 23 children (0.03%), and ametropic amblyopia in 12 children (0.01%). The number of children with strabismus of unknown type was 245 (0.28%) while the number of children with amblyopia of unknown type was 81 (0.09%).
Conclusions: The prevalence rates of strabismus and amblyopia in this population of Japanese elementary school children were lower than those reported in Western countries. The exotropia/esotropia ratio were increased in comparison with past studies in Japan. The school eye doctors need to be more diligent in identifying and diagnosing various types of strabismus and amblyopia in order to contribute to the school vision screening program already in place in Japan.

DOI： 10.1080/092865804909007805

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Language：English   Publisher：TAYLOR & FRANCIS INC  

Purpose: To show the feasibility of vitrectomy and silicone oil tamponade as an initial surgical procedure for retinal detachments with multiple tears that develop after the fulminant type of acute retinal necrosis syndrome. Methods: In a prospective noncomparative interventional case series, vitrectomy, silicone oil tamponade, and encircling scleral buckling with a solid silicone, combined with phacoemulsification and intraocular lens implantation (except for one pseudophakic patient [Case 2]), were performed in three consecutive patients during the four-year period from 1999 to 2002. These patients had developed retinal detachment with multiple retinal tears after the resolution of acute retinal necrosis syndrome. As an initial standard treatment for acute retinal necrosis syndrome, all patients received maximum-dose intravenous acyclovir (1500 mg daily) for two weeks combined with intravenous prednisolone tapered from 200 mg daily. Results: Case 1 was a 65-year-old woman who developed retinal detachment 44 days after the onset of acute retinal necrosis syndrome; Case 2, a 79-year-old man, developed retinal detachment 51 days after the onset; and Case 3, a 59-year-old man, developed retinal detachment 70 days after the onset. Before surgery, all patients showed multiple tears scattered on the detached atrophic retina extending over the entire midperipheral fundus with vitreoretinal adhesions and vitreous opacity. The retina was reattached during the initial surgery. The patients showed no recurrence of retinal detachment and maintained a visual acuity of 20/200 or 20/100 during the one- to three-year follow-up period. Conclusions: Vitrectomy and silicone oil tamponade could be a treatment option as the initial surgical procedure for retinal detachments that develop after the fulminant type of acute retinal necrosis syndrome.

DOI： 10.1080/09273940490518838

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Language：English   Publisher：BLACKWELL PUBLISHING INC  

Photoelectric dyes, which absorb light and convert photon energy to electric potentials, have been previously shown to stimulate retinal neurons in culture. In this study, a photoelectric dye was coupled to a polyethylene film surface and tested in vitro using retinal tissues from chick embryos at the 12-day embryonic stage, at which time outer segments of retinal photoreceptor cells have not yet developed. Carboxyl moieties were introduced to a polyethylene film surface by fuming nitric acid, and then a photoelectric dye, 2-[2-[4-(dibutylamino)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide, was coupled to the film through amide linkage. Intracellular calcium elevation was observed with Fluo-4 in retinal tissues placed on the dye-coupled polyethylene film, in contrast to retinal tissues which had no contact with the film. The response was inhibited by calcicludine, a voltage-gated calcium channel blocker, and also by extracellular calcium depletion. The photoelectric dye, coupled to the polyethylene film surface, absorbed light under a dissecting microscope and stimulated neurons in retinal tissues, showing that the dye-coupled film could be used as a prototype of retinal prostheses.

DOI： 10.1111/j.1525-1594.2004.29010.x

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The aim of this study was to test whether cyclic tetrasaccharide could prevent cataract formation in isolated porcine lenses in vitro. Porcine eyes were cut at the midperiphery with a razor blade and pressure was applied to the globe to eject the lens without touching. The isolated lenses were then washed with saline and transferred with a spoon to wells of a 24-well multidish with a lid. The lenses were incubated in saline, 1, 10, 20, 50, 75, and 100 mM trehalose or cyclic tetrasaccharide in saline for 40 days at room temperature and in room humidity. Solution change or aeration was not done during the period. The lenses were observed with a dissecting microscope with transmitting light source and the images of the lenses were captured through a CCD camera into a computer. The lens opacity was measured as mean density in a circle area placed inside the lens. Cyclic tetrasaccharide at 75 mM and 100 mM concentrations significantly delayed the development of lens opacity compared with saline, trehalose at any concentrations, and cyclic tetrasaccharide at 50 mM or lower concentrations over the course of 40 days. The lenses in 100 mM cyclic tetrasaccharide showed transient surface opacity on the initial phase of incubation up to 5 days and then became transparent. In conclusion, cyclic tetrasaccharide delays the development of lens opacity in vitro. Cyclic tetrasaccharide might be used as a cataract-delaying agent. © Mary Ann Liebert, Inc.

DOI： 10.1089/cpt.2005.3.238

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DOI： 10.11477/mf.1410100200

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Purpose: To report a patient who developed systemic malignant lymphoma 17 years after bilateral orbital pseudotumor.
Case: A 24-year-old man developed bilateral orbital pseudotumor. He was stable until 17 years later, when he was afflicted with systemic malignant lymphoma, a diffuse large B-cell lymphoma, and he died of the disease. He showed no new orbital lesion at the presentation of systemic lymphoma. Pathological diagnosis at autopsy was systemic malignant lymphoma with bilateral orbital pseudotumor.
Methods: Immunohistochemical reexamination of the paraffin-embedded tissue and polymerase chain reaction of paraffin sections.
Results: Histopathologically, the orbital masses resected on different occasions consisted of small lymphocytes and plasma cells. Immunohistochemical staining revealed an immunoglobulin light chain K and lambda bitype of B-cell lymphocytes and plasma cells. In contrast, the cervical lymph node showed large lymphoma cells that were positive only for lambda light chain, indicative of a lambda monotype. Amplification by polymerase chain reaction of the immunoglobulin heavy chain gene from paraffin sections demonstrated clonal rearrangement in the cervical lymph node but showed no clonality in the orbital tumor, supporting altogether the diagnosis of orbital pseudotumor.
Conclusion: Orbital pseudotumor should be carefully followed for possible development of systemic malignant lymphoma. (C) Japanese Ophthalmological Society 2004.

DOI： 10.1007/s10384-004-0095-6

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Purpose: Trehalose eyedrops were found by a previous study to be safe and effective compared with saline in the treatment of moderate-to-severe dry eye syndrome. The present study was designed to compare the efficacy of trehalose eyedrops with that of the commercially available eyedrops containing hyaluronan or cellulose now used in the treatment of moderate-to-severe dry eye syndrome.
Methods: In a randomized, double-masked, 4-week crossover, controlled clinical trial, 36 patients with moderate-to-severe dry eye syndrome were divided into two groups: the hyaluronan (Hyalein)comparison group (18 patients) and the hydroxyethylcellulose (Mytear)-comparison group (18 patients). Each group used either trehalose or one of the commercially available medications contained in a masked eyedrop container for the first 4 weeks, and then for the second 4 weeks, switched to either trehalose or the commercial eyedrop not used for the first 4 weeks. Symptoms and signs in both eyes were recorded at the baseline, at 4 weeks, and at 8 weeks.
Results: At 4 weeks after the treatment, fluorescein and rose bengal staining scores of the ocular surface as well as the tear film breakup time had improved significantly with trehalose eyedrops compared with the commercially available eyedrops containing either hyaluronan or hydroxyethyleellulose (P &lt; 0.001, Wilcoxon signed ranks test). In addition, all the objective signs were significantly better in patients who finished with trehalose at the end of the 8-week trial compared with those who finished with either of the two commercially available drugs. A larger number of patients evaluated trehalose as a better treatment than the commercially available eyedrops.
Conclusions: Trehalose solution was a better treatment for moderate-to-severe dry eye syndrome in comparison with two commercially available eyedrops containing hyaluronan or hydroxyethylcellulose. (C) Japanese Ophthalmological Society 2004

DOI： 10.1007/si10384-004-0085-8

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Purpose: To elucidate the long-term prognosis of biopsy-proven malignant lymphoma of conjunctival origin after a treatment option of observation or radiation.
Design: Prospective noncomparative interventional case series.
Participants: Thirteen patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of conjunctival origin.
Methods: In the 11-year period from 1992 to 2002, 13 consecutive patients (7 female and 6 male) with ages ranging from 32 to 68 years (mean, 57) who showed malignant lymphoma of conjunctival origin were enrolled in the study. Histopathological and immunohistochemical studies of biopsy specimens of the conjunctival lesions proved extranodal marginal zone B-cell lymphoma of MALT in all patients. At the initial visit, magnetic resonance imaging (MRI) showed no orbital tumors, and gallium scintigraphy demonstrated no systemic involvement. The patients chose observation or radiation after the biopsy.
Main Outcome Measures: Clinical disappearance of the conjunctival lymphoma lesions.
Results: Five patients chose 30-Gy radiation to the remaining conjunctival lesions after the biopsy, whereas the other 8 patients were simply observed without administration of any medication. During the follow-up, ranging from 1 to 11 years (mean, 5.4), 7 of these 8 patients without radiation showed spontaneous regression of the conjunctival lesions 1 to 5 years after the biopsy. Yearly MRI of the orbit and gallium scintigraphy disclosed no lesions in any of the patients.
Conclusions: A large fraction of patients with MALT lymphoma of conjunctival origin had spontaneous regression after the biopsy. Follow-up without radiation is an option for patients with MALT lymphoma of conjunctival origin after the pathologic diagnosis by biopsy. (C) 2004 by the American Academy of Ophthalmology.

DOI： 10.1016/j.ophtha.2003.09.049

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Purpose: To study the clinical relevance of sequence alterations in the optineurin gene (OPTN) among Japanese patients with open-angle glaucoma, including both primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Methods: Genomic DNA was isolated from 83 patients with open-angle glaucoma (55 with POAG and 28 with NTG) and 58 control subjects. The 13 exons of OPTN corresponding to the coding region were amplified by polymerase chain reaction and directly sequenced. Clinical factors were compared between glaucoma patients with and without a certain nucleotide change. Results: The reported heterozygous mutations, c.458G &gt
A(Glu50Lys) in exon 4 and c.691_692insAG in exon 6, were not found in any glaucoma patients or control subjects. The reported c.603T &gt
A(Met98Lys) in exon 5 was significantly more prevalent in the POAG (8/55, 14.5%, p = 0-0147) and NTG (4/28, 14.2%, p = 0-0369) patients, and even in both the POAG and NTG patients combined (12/83, 14-4%, p = 0.0149, Fisher exact probability test), than in the control subjects (1/58, 1.7%). The rates of the reported c.1944G &gt
A(Arg545Gln) in exon 16 were not significantly different between open-angle glaucoma patients (3/83, 3.6%) and control subjects (4/58, 6.8%). In addition, a heterozygous change, c.412G &gt
A(Thr34Thr) in exon 4 was found in 18 (21.6%) open-angle glaucoma patients and seven (12.0%) control subjects. Another heterozygous change, c.457C &gt
T(Thr49Thr), in exon 4 was found only in three POAG patients. The 18 open-angle glaucoma patients with c.412G &gt
A showed significantly larger cup-to-disc ratios (p = 0-0178, Mann-Whitney U test), significantly more deteriorated mean deviations of the visual field in the left eye at the final visit (p = 0.0076), and a significantly higher rate of surgery and/or laser history (p = 0.0321, Fisher exact probability test) than the 65 open-angle glaucoma patients without the nucleotide change. Conclusions: Met98Lys is a risk-associated alteration for open-angle glaucoma, including POAG and NTG, in the Japanese population as initially reported. The amino acid-preserving polymorphism, c.412G &gt
A, may be a genetic risk factor for the progression of open-angle glaucoma in this Japanese population.

DOI： 10.1080/13816810490514298

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

DOI： 10.1136/bjo.2003.021527

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DOI： 10.11477/mf.1410100830

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PURPOSE: To arrive at an understanding of the differences in gene and protein expression between human lateral and medial rectus muscle tissue excised from strabismic patients. METHODS: Resected fragments of the lateral and medial rectus muscles obtained during strabismus surgery were frozen under liquid nitrogen and pulverized by a Freezer/Mill system. Radiolabelled cDNA was synthesized from polyA+ RNA and hybridized with a gene array nylon membrane (Atlas Human 1.2 Array) to detect the difference in gene expression between the lateral and medial rectus muscles. Based on the gene array results, tissue inhibitor of metalloproteinases (TIMP)-1 and 2, matrix metalloproteinase (MMP)-2, and bone morphogenetic protein (BMP)-4 were measured in solubilized muscle tissues by enzyme immunoassay and normalized by unit length of resection. RESULTS: The resected lateral rectus muscle had significantly smaller amounts of TIMP-1,TIMP-2 and BMP-4 but larger amounts of MMP-2 compared to the medial rectus muscle (P &lt
0.001, Mann-Whitney U test).The amounts of TIMP-1 in the muscle when the lateral and medial rectus were combined were positively correlated with TIMP-2 and BMP-4, while the amounts of TIMP-2 positively correlated with BMP-4 (P &lt
0.001, Spearman rank correlation test). The amounts of BMP-4 in both muscles increased significantly with age (P = 0.0003). CONCLUSIONS: Resected tissue from the lateral and medial rectus muscles had different levels of expression of TIMP-1 and 2, MMP-2, and BMP-4. These molecular differences may underlie different characteristics of the two extraocular muscles and may also influence the process of wound healing after strabismus surgery.

DOI： 10.1076/stra.11.3.145.16647

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Purpose: To elucidate protein expression, genomic structure, and genomic polymorphisms of a novel gene, 'oculomedin', that has been cloned as a mechanical stretch-response gene from human trabecular cells in culture. Methods: Polyclonal antibody was prepared by immunizing rabbits with a chemically synthesized 15-mer peptide of oculomedin. Protein expression was revealed by Western blot analysis after polyacrylamide gel electrophoresis of extracts of mechanically stretched trabecular cells and control trabecular cells in culture as well as retinal tissue. Protein localization was studied immunohistochemically in the human eye section. Genomic structure was determined by searching the GenBank database. Genomic polymorphisms of the coding region in 163 glaucoma patients and 50 normal subjects were detected by PCR amplification and direct sequencing. Results: Western blot analysis showed that oculomedin protein was expressed only in stretched trabecular cells, not in control trabecular cells in culture. Immunohistochemically, oculomedin protein was localized to the trabecular meshwork, Schlemm's canal endothelium, retinal photoreceptor cells, and corneal and conjunctival epithelium. The oculomedin gene (OCLM) consists of two exons which are located inside an intron of a different gene of unknown function (C1orf27) on chromosome 1q25, near and telomeric to myocilin (MYOC). Two types of heterozygous nucleotide substitutions resulting in amino acid changes were found in two of 75 patients with primary open-angle glaucoma, but not at all in patients with other types of glaucoma or in normal subjects. Conclusions: Oculomedin may play a role in the function of the trabecular meshwork and also in the development of primary open-angle glaucoma.

DOI： 10.1076/opge.24.3.141.15604

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

The purpose of this study was to elucidate the role of extracellular matrix components such as aggrecan, fibronectin, and laminin in the extraocular muscle of patients with strabismus. Resected tissues of the medial rectus muscle of 47 patients with intermittent exotropia obtained during recession-resection surgery were frozen under liquid nitrogen and pulverized by a Freezer/Mill to solubilize the tissue for enzyme immunoassay. The total amounts of aggrecan, fibronectin, and laminin in the resected tissue were correlated with clinical data of patients such as age, exodeviation, and refractive error. The amount of aggrecan decreased significantly with the advance of age (P &lt; 0.0001, Spearman rank correlation test), while the amount of laminin or fibronectin had no correlation with age. Patients with basic type intermittent exotropia showed larger, although not significantly, amounts of aggrecan than those with convergence insufficiency type (P = 0.0538, Mann-Whitney U-test). The amount of aggrecan may be related to motor aspects of intermittent exotropia.

DOI： 10.18926/AMO/32803

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

DOI： 10.18926/AMO/32824

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

DOI： 10.18926/AMO/32833

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Language：English   Publisher：ELSEVIER SCIENCE INC  

Purpose: To elucidate the genetic or environmental background for clinical features in the three major types of comitant strabismus.
Methods: Interview based on a questionnaire asking background factors such as family history of strabismus and abnormalities in pregnancy and delivery was conducted with 101 consecutive patients with infantile esotropia (5-180 months of age), 83 with accommodative or partially accommodative esotropia (6-201 months of age), and 143 with intermittent exotropia (3-216 months of age) seen during 7 months from May to November 1998. The clinical features of strabismus obtained from medical records were analyzed statistically by logistic regression to determine their relation with these background factors.
Results: In infantile esotropia, patients with family history of strabismus had a significantly higher chance of showing latent nystagmus (odds ratio, 3.553; 95% confidence interval [CI], 1.077-11.717; P=.0373, logistic regression analysis). In a subgroup of 40 patients with infantile esotropia whose birth followed no abnormalities in pregnancy or delivery, patients with family history of strabismus had a significantly higher chance of showing inferior oblique muscle overaction (odds ratio, 7.714; 95% CI, 1.246-47.761; P=.0280), dissociated vertical deviation (odds ratio, 6.667; 95% CI, 1.176-37.787; P=.0321), and latent nystagmus (odds ratio, 7.333; 95% CI, 1.168-46.060; P=.0336). In accommodative or partially accommodative esotropia and intermittent exotropia, no relation was found between the clinical features and the background factors.
Conclusions: Inferior oblique muscle overaction, dissociated vertical deviation, and latent nystagmus in infantile esotropia might have a genetic background.

DOI： 10.1016/S0021-5155(02)00685-8

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DOI： 10.11477/mf.1410101452

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Language：English   Publisher：SWETS AND ZEITLINGER B V  

To elucidate the long-term visual outcome of primary microtropia, a retrospective review was made on 31 patients with 5 years or more (5-16 years, mean: 9.2 years) follow-up. All patients showed anomalous retinal correspondence, peripheral fusion, 10 prism diopters or smaller esodeviation at the initial and final visit. At the initial visit, TNO stereoacuity was absent in 25 patients, 480 seconds in 2, and 240 seconds in 4. The visual acuity was 20/20 or better in both eyes of 16 patients, but 20/30 or worse in either eye or both eyes of 15 patients. At the final visit, the 25 patients with no stereoacuity still showed no stereoacuity while stereoacuity remained unchanged or got better in the 6 patients with initial stereoacuity of 480 seconds or better. The visual acuity in 7 of the 15 patients with 20/30 or worse became 20/20 or better while remained 20/30 or worse in the other 8 patients. No relation was found between no TNO stereoacuity and poor visual acuity. Patients with primary microtropia could be largely classified into those with no stereoacuity throughout the course and those with some levels of stereoacuity which had a chance to get better during the follow-up.

DOI： 10.1016/S0021-5155(03)00105-9

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DOI： 10.11477/mf.1410101459

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Purpose: To describe bilateral optic neuritis that occurred as an adverse effect of recombinant and natural interferon α administration. Methods: Report of two cases. Case 1, a 62-year-old woman, developed bilateral optic neuritis with decreased sensation of vibration and increased deep tendon reflex in the lower extremities after a seven-month use of recombinant interferon α-2a for chronic active hepatitis C. Case 2, a 29-year-old woman, developed bilateral optic neuritis combined with numbness of the lower extremities as well as bowel and bladder dysfunction after a 22-month use of recombinant interferon α-2b for chronic myelogenous leukemia. After a two-month interruption of interferon administration, natural interferon α was given but followed by another episode of the same neurological manifestations. Results: In both cases, magnetic resonance imaging demonstrated multiple small high-intensity areas in the cerebral white matter and spinal cord, while cerebrospinal fluid examination disclosed mononuclear cell increase and protein elevation including myelin basic protein, all of which simulated the features of multiple sclerosis. The two patients underwent several courses of pulse corticosteroid therapy, each course consisting of three days of methylprednisolone 1000 mg daily, resulting in visual recovery to some extent. Conclusions: Optic neuritis in combination with other neurological signs, simulating multiple sclerosis, should be included in the list of adverse effects of recombinant and natural interferon α administration.

DOI： 10.1076/ocii.10.4.299.15588

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Objective: Trehalose can protect human corneal epithelial cells in culture from death from desiccation. This study was designed to test the efficacy and safety of trehalose eyedrops in the treatment of moderate to severe dry eye syndrome.
Design: A randomized, double-masked, dose-ranging, fellow eye-controlled clinical trial.
Participants: Thirty-four patients with moderate to severe dry eye syndrome.
Methods: The patients used either 100 or 200 mM trehalose dissolved in saline six times daily in one eye and control saline in the other eye for 4 weeks.
Main Outcome Measures: Symptoms and signs in both eyes were recorded separately at baseline, 2 weeks, and 4 weeks.
Results: Fluorescein and rose bengal staining scores of the ocular surface improved at both 2 weeks and 4 weeks in the eyes with 100 and 200 mM trehalose, compared with eyes with control saline (P = 0.0030 to P &lt; 0.0001, respectively, Mann-Whitney U test). Tear film breakup time became significantly longer at 2 weeks and 4 weeks with 100 mM trehalose (P = 0.0024 and P &lt; 0.0001, respectively), but not with 200 mM trehalose. No adverse effect attributable to trehalose solution was noted.
Conclusions: Trehalose solution was an effective and safe eyedrop for the treatment of moderate to severe dry eye syndrome in this group of patients. (C) 2002 by the American Academy of Ophthalmology, Inc.

DOI： 10.1016/S0161-6420(02)01219-8

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Purpose: To describe a case with frosted branch angiitis occurring in association with manifestations of Harada disease.
Case: A 41-year-old man developed marked iridocyclitis, frosted branch angiitis and retinal white dots, together with serous detachment of the sensory retina in the posterior pole of both eyes.
Observations: Fluorescein angiography demonstrated multiple retinal pigment epithelial leakage points in the early phase followed by late dye pooling in the serous detachment, consistent with the manifestations of Harada disease. The patient experienced recurrence of the same combination of manifestations 10 years later. On both occasions, he showed mononuclear cell increase and protein elevation in the cerebrospinal fluid on spinal tap.
Conclusion: Fluorescein angiography and spinal tap supported the diagnosis of Harada disease in the patient. The present patient could be diagnosed as having either Harada disease with frosted branch-like response or frosted branch angiitis with serous retinal detachment as occurs in Harada disease. (C) 2000 Japanese Ophthalmological Society.

DOI： 10.1016/S0021-5155(02)00564-6

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Purpose: To explore the role of human herpesvirus-8 (HHV-8) in the pathogenesis of uveitis and other forms of ocular inflammation. Methods: Serum antibody titers to HHV-8 were measured in 76 patients with uveitis from various causes and other types of ocular inflammation in either the acute phase, the convalescent phase, or both. Results: Only one 21-year-old male patient in the convalescent phase of unilateral pars planitis showed a positive titer for HHV-8. His serum was negative for human immunodeficiency virus-1. Conclusions: Although the seropositive rate in the patient population was higher than that in the general population, the increased incidence was not statistically significant. The role of HHV-8 in the pathogenesis of intraocular inflammation appears to be limited.

DOI： 10.1076/ocii.10.3.197.15602

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Language：English   Publisher：KARGER  

Purpose: To present young monozygotic twins both of whom developed choroidal neovascularization at the same time. Case/Observations: Monozygotic twins, 22-year-old women, who lived in the same house, developed choroidal neovascularization in the left eye at the same time. The degree of myopia was higher in the left eye (-7.75 and -8.5 dpt in spherical equivalent) than in the right eye (-6.75 and -4.5 dpt) of both patients. The choroidal neovascularization regressed in a different time course and the visual acuity returned to normal in both patients. Conclusion: This pair of monozygotic twins suggests that both genetic and environmental factors underlie the development of choroidal neovascularization in myopic eyes. Copyright (C) 2002 S. Karger AG, Basel.

DOI： 10.1159/000063840

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Language：English   Publisher：SPRINGER-VERLAG  

Purpose: To identify risk factors for diabetic choroidopathy in patients with type 2 diabetes. Methods: Forty-five consecutive patients with diabetic retinopathy underwent simultaneous indocyanine green angiography (ICG) and fluorescein angiography using a double detector and confocal scanning laser ophthalmoscopy in both eyes. Choroidal vascular abnormalities were evaluated by comparing the angiographic findings derived from the two methods. We analyzed the association between the presence of abnormal choroidal lesions evident on ICG angiography and several risk factors. Results: Choroidal abnormalities evident on ICG angiography but not on fluorescein angiography included hypofluorescent spots in 72 eyes (80%) of 40 patients (89%), small hyperfluorescent spots in 61 eyes (68%) of 35 patients (78%), and large hyperfluorescent spots in 32 eyes (36%) of 21 patients (47%). The severity of diabetic retinopathy was significantly associated with the presence of hypofluorescent spots (P=0.002, Cochran-Armitage test) in both eyes and with the small hyperfluorescent spots in the right eyes (P=0.047, Cochran-Armitage test). Glycosylated hemoglobin levels were significantly associated with the large hyperfluorescent spots in the right eyes (P=0.003, Fisher's exact probability test), and the treatment regimen was significantly associated with the small hyperfluorescent spots in the left eyes (P=0.048, chi-square test). Conclusion: These data suggest that risk factors influencing the prevalence of diabetic choroidopathy in patients with type 2 diabetes mellitus may include severity of diabetic retinopathy, degree of diabetic control and treatment regimen.

DOI： 10.1007/s00417-002-0451-5

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Purpose: To present submacular exudates as a manifestation of cat scratch disease. Methods: Report of two cases. Results: The first patient, a 34-year-old man, developed submacular exudates with serous retinal detachment ten days after having axillary lymphadenopathy and fever. The second patient, a 30-year-old woman, developed submacular exudates with serous retinal detachment mimicking central serous chorioretinopathy. Fluorescein angiography revealed late staining of the subretinal lesions in both cases. The lesion resolved spontaneously in the first patient, while sulfamethoxazole and trimethoprim was required for the second patient. Both patients had a positive IgG titer for Bartonella henselae. Conclusions: Submacular exudates with serous retinal detachment can occur in cat scratch disease. Cat scratch disease should be included in the differential diagnosis of submacular exudates with central serous chorioretinopathy.

DOI： 10.1076/ocii.10.2.147.13979

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Language：English   Publisher：ELSEVIER SCIENCE INC  

PURPOSE: To present acute posterior multifocal placoid pigment epitheliopathy and scleritis occurring in association with pANCA (perinuclear antineutrophil cytoplasm mic antibody),positive systemic vasculitis.
DESIGN: Interventional case report.
METHODS: A 69-year old woman developed bilateral acute posterior multifocal placoid pigment epitheliopathy concurrent with rapidly progressive glomerulonephritis and bronchioalveolitis in both lungs.
RESULTS: The patient showed a high titer of pANCA (myeloperoxidase,ANCA). She then developed scleritis in the left eye and multiple gastric ulcers.
CONCLUSION: Acute posterior multifocal placoid pigment epitheliopathy and scleritis in this patient are manifestations that are part of pANCA-positive systemic vasculitis. This association further supports that acute posterior multifocal placoid pigment epitheliopathy is caused by vasculitic inflammation of the choriocapillaris. (C) 2002 by Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0002-9394(01)01369-1

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Language：English   Publisher：BRITISH MED JOURNAL PUBL GROUP  

Aims: To describe the results of a study of the incidence of conjunctival ulceration and its pathology as a manifestation of Behcet's syndrome.
Methods: The authors reviewed retrospectively medical charts of 152 patients with Behcet's syndrome seen at the uveitis service of Okayama University Hospital from January 1995 to December 1999. Criteria used to diagnose Behcet's syndrome in this study required the presence of oral aphthous ulceration plus any two of three other manifestations-genital ulceration, eye lesions such as iridocyclitis uveoretinitis, or skin lesions such as erythema nodosum. The presence of conjunctival ulceration was determined in patients with Behcet's syndrome through standardised ophthalmological examinations. A biopsy of the conjunctival ulceration was performed in one patient. The incidence of conjunctival ulceration in patients with Behcet's syndrome was calculated and the clinical and pathological features of this ulceration were examined.
Results: Four of 152 patients (2.6%) developed conjunctival ulceration in concordance with exacerbation of their systemic symptoms. Histopathological examinations of a conjunctival biopsy specimen in one patient revealed intraepithelial and perivascular infiltration with neutrophils and lymphocytes consistent with Behcet's syndrome. The conjunctival ulcerations of the study patients showed good response to topical corticosteroids or topical steroids plus oral colchicine.
Conclusions: Conjunctival ulceration should be noted as an uncommon but possible manifestation of Behcet's syndrome. Accordingly, routine examination of the conjunctival is recommended in patients with Behcet's syndrome, and Behcet's syndrome should be included in a list of differential diagnoses for patients with conjunctival ulcerations.

DOI： 10.1136/bjo.86.2.140

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Language：English   Publisher：ELSEVIER SCIENCE INC  

Objective: To explain fluorescein angiographic features in patients with tubulointerstitial nephritis and uveitis syndrome.
Design: Retrospective observational case series.
Participants: Four consecutive patients with tubulointerstitial nephritis and uveitis syndrome seen at Uveitis Service of Okayama University Hospital from 1995 to 2000.
Methods: Patients' characteristics obtained from medical records were analyzed. In addition, characteristics of 15 patients reported previously as case reports in the Japanese literature were reviewed.
Main Outcome Measures: Clinical and fluorescein angiographic features.
Results: The present four patients showed varying degrees of retinal capillary leakage on fluorescein angiography, ranging from capillary leakage limited to the peripheral fundus to cystoid macular edema. The same angiographic features were found in 15 patients reported previously in the Japanese literature.
Conclusions: Retinal capillary leakage of varying degrees was a common fluorescein angiographic feature in patients with tubulointerstitial nephritis and uveitis syndrome. Fluorescein angiography is valuable in assessing the extent of retinal involvement. (C) 2002 by the American Academy of Ophthalmology.

DOI： 10.1016/S0161-6420(01)00850-8

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Language：English   Publisher：ELSEVIER SCIENCE INC  

Purpose: The concordance of strabismic phenotypes was examined in monozygotic versus multizygotic twins and other multiple births to study the role of genetic background in different types of comitant strabismus.
Methods: Medical charts of 45 consecutive pairs of twins (16 monozygotic and 18 dizygotic twins, and 11 with unknown zygosity), 3 sets of triplets (one monozygotic and 2 trizygotic triplets), and one set of quadruzygotic quadruplets examined at 6 institutions between 1973 and 1999 were reviewed retrospectively. The concordance was defined as both or all members having either esotropia or exotropia in common.
Results: The concordance of strabismic phenotypes was noted in 33 of 49 pairs or sets (67.3%): 14 of 17 monozygotic twins or triplets (82.4%), 10 of 21 multizygotic twins, triplets, or quadruplets (47.6%), and 9 of 11 twins with unknown zygosity (81.8%). The concordance rate was significantly higher in monozygosity than in multizygosity (P = .043, Fisher exact probability test). The predominant concordant phenotypes in monozygosity were accommodative esotropia and intermittent exotropia.
Conclusion: A high concordance rate of strabismic phenotypes, predominantly of accommodative esotropia and intermittent exotropia in monozygosity, suggests the genetic background for these types of strabismus. (C) 2002 Japanese Ophthalmological Society.

DOI： 10.1016/S0021-5155(01)00465-8

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Language：English   Publisher：ELSEVIER SCIENCE INC  

Purpose: To report multiple occlusive retinal arteritis as a complication of rheumatoid arthritis.
Case: A 67-year-old woman developed superotemporal branch retinal artery occlusion in both eyes, together with arterial sheathing and large cotton wool patches around the optic disc, in the course of rheumatoid arthritis with moderate activity.
Observations: Fluorescein angiography disclosed delayed filling of the superotemporal retinal artery in the right eye and no filling of the superotemporal artery in the left eye, In addition, segmental absence of filling was found in peripheral branches of the other major retinal arteries in both eyes. After hyperbaric oxygen therapy and intravenous administration of prostaglandin E1 and urokinase for 2 weeks, there was improvement in her vision.
Conclusion: Multiple occlusive retinal arteritis in rheumatoid arthritis can manifest as retinal artery occlusion. Rheumatoid arthritis should be included in the differential diagnosis of bilateral retinal artery occlusion. (C) 2001 Japanese Ophthalmological Society.

DOI： 10.1016/S0021-5155(01)00410-5

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