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Purpose: To investigate whether variants in the ARMC9 gene encoding KU-MEL-1 are associated with Vogt-Koyanagi-Harada (VKH) disease in a Japanese population.Methods: We recruited 380 Japane...

Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.

To determine the relationship between the peripapillary choroidal thickness (ppCT) and the degree and distribution of the tessellation in the fundus of normal eyes. This was a prospective, observational cross-sectional study of 118 right eyes of young healthy volunteers. The ppCT was measured from the optical coherence tomography (OCT) circle scans manually at eight sectors: the nasal, supranasal superior, supratemporal, temporal, infratemporal, inferior, and infranasal sectors. The subjective degree of the tessellation in the color fundus photographs (CFPs) was classified into three categories: non-tessellated (NT), weakly tessellated (WT), and strongly tessellated (ST) in same sectors. The objective degree of tessellation designated by the tessellation fundus index (TFI) which was calculated as TFI = (R − G)/(R + G + B) using the mean value of the red-green-blue intensities of the CFPs. The differences in the ppCT and TFI for the three tessellation groups were analyzed. The correlations between the TFI and the ppCT were also determined. The mean age of the subjects was 25.8 years and the mean axial length of the eye was 25.5 mm. The inter-rater agreement of the subjective classifications was high with a Fleiss kappa of 0.71. The ppCT was significantly thinner in eyes with higher degrees of tessellation (P

To determine the correlations between the retinal nerve fiber layer thickness (RNFLT) and the axial length, peripapillary retinal tilt (PRT), and optic disc size, and retinal artery position.A prospective, observational cross-sectional study of 119 healthy right eyes of 119 volunteers. All participants underwent comprehensive ophthalmologic examinations including peripapillary RNFLT imaging and measurements of the axial length. The RNFLT was determined by the TOPCON 3D OCT-1000, MARK II. The RNFLT in a 3.4 mm circular scan was divided into 12 clock-hour sectors and 4 quadrant sectors around the optic disc. The PRT was assessed using the RNFLT B-scan images. The angle between the supra-temporal and infra-temporal retinal arteries was determined in the color fundus photographs. The correlations between the sectorial RNFLTs and the axial length, PRT, optic disc size, and artery angles were determined by simple and multiple regression analyses.Multiple regression analyses showed that the nasal and inferior quadrants and the whole RNFLT were significantly and negatively correlated with the axial length (standardized coefficient (SC)=-0.39 to -0.30, P0.05). The PRT was significantly and positively associated with all of the quadrants and the whole RNFLT (SC=0.22 to 0.45, P0.05). The retinal artery angle was significantly and negatively associated with the temporal RNFLT and positively associated with inferior RNFLT (SC=-0.49 to 0.31, P0.05). The optic disc size was significantly and positively associated with the superior and nasal quadrants, and the whole RNFLT (SC=0.20 to 0.27, P0.05).The axial length, PRT, optic disc size, retinal artery angle can affect the peripapillary RNFLT. These variables should be considered when assessing the peripapillary RNFLT.

BackgroundHuman T-lymphotropic virus type 1 (HTLV-1) carriers may develop severe systemic diseases, such as adult T cell leukaemia (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This study aims to investigate systemic diseases of HTLV-1 carriers who had developed HTLV-1-associated uveitis (HAU).MethodsWe investigated the occurrence of systemic diseases in 200 patients with HAU by performing a retrospective investigation of their medical records and examining the results of a postal survey.ResultsThe mean age of HAU onset was 49 years, and the total person-years from HAU onset was 1627. There were two cases of ATL. Of these, one was diagnosed with smouldering ATL at the time of HAU onset and the other developed acute-type ATL 4 years after HAU onset. There were 26 cases of HAM/TSP; of these, HAM/TSP occurred first in 13 cases and HAU occurred first in 11 cases. The interval between the onset of HAM/TSP and HAU ranged from 6 months to 6 years, with no significant difference observed based on whether HAM/TSP or HAU occurred first. Hyperthyroidism was noted in 45 cases and preceded onset in all cases. HAU onset occurred after starting thiamazole treatment, and in two cases HAU recurred each time thiamazole treatment was restarted.ConclusionHTLV-1 carriers with HAU may develop HAM/TSP more frequently than general carriers. HTLV-1 carriers undergoing treatment for hyperthyroidism may be prone to developing HAU.

Purpose Artificial intelligence (AI) can identify the sex of an individual from color fundus photographs (CFPs). However, the mechanism(s) involved in this identification has not been determined. This study was conducted to determine the information in CFPs that can be used to determine the sex of an individual. Methods Prospective observational cross-sectional study of 112 eyes of 112 healthy volunteers. The following characteristics of CFPs were analyzed: the color of peripapillary area expressed by the mean values of red, green, and blue intensities, and the tessellation expressed by the tessellation fundus index (TFI). The optic disc ovality ratio, papillomacular angle, retinal artery trajectory, and retinal vessel angles were also quantified. Their differences between the sexes were assessed by Mann-Whitney U tests. Regularized binomial logistic regression was used to select the decisive factors. In addition, its discriminative performance was evaluated through the leave-one-out cross validation. Results The mean age of 76 men and 36 women was 25.8 years. The regularized binomial logistic regression delivered the optimal model for sex selected variables of peripapillary temporal green and blue intensities, temporal TFI, supratemporal TFI, optic disc ovality ratio, artery trajectory, and supratemporal retinal artery angle. With this approach, the discrimination accuracy rate was 77.9%. Conclusions Human-assessed characteristics of CFPs are useful in investigating the new theme proposed by AI, the sex of an individual. Translational relevance This is the first report to approach the thinking process of AI by humans and can be a new approach to medical AI research.

Purpose To determine the effect of the axial length on the supernormal and false-positive sectors of the peripapillary retinal nerve fibre layer (RNFL) in healthy eyes using the normative database embedded in a spectral domain optical coherence tomographic (SD-OCT) instrument. Methods This was a prospective, observational cross -sectional study. The right eyes of 126 healthy young volunteers were studied. The RNFL thickness was measured by SD-OCT in twelve 30-degree sectors (clock hours) around the optic disc. The sectors whose RNFL thickness was 95% probability level were labelled as supernormal sectors. The relationships between the axial length and rates of supernormal and false-positive sectors were investigated. Results A longer axial length was significantly associated with an increase in the rates of supernormal thickness in sector 8 (odds ratio, [OR], 1.494; p = 0.010) and sector 10 (OR, 1.529; p = 0.008). The supernormal sectors were mainly located in the temporal region. A longer axial length was significantly associated with a higher rates of false positives in sector 5 (OR, 1.789; p = 0.017), sector 6 (OR, 2.305; p

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome associated with extraocular malignancies. Extraocular pigmented lesions have been reported. We report that two patients with BDUMP presented with non-ocular pigmented lesions.

PURPOSE Eyes with a peripapillary nerve fiber elevation (pNFE) are those with a discrepancy between the optic disc margin in a color fundus photograph and the Bruch's membrane opening in an optical coherent tomographic (OCT) cross-sectional image. The purpose of this study was to determine the prevalence of pNFE in young healthy eyes, and to compare the axial length and optic disc tilt between pNFE and non-pNFE groups. METHODS This was a prospective, observational, cross-sectional study of 117 right eyes. All participants (mean age 25.8 ± 4.0 years) underwent a comprehensive ophthalmologic examination. The pNFE was determined from the color fundus photographs, scanning laser ophthalmoscopic images, and optic disc cross-sectional OCT images. The degree of optic disc tilt was determined by the sine curve technique. Mann-Whitney U tests were used to determine the significance of the differences in the axial length and optic disc tilt between the pNFE and non-pNFE groups. RESULTS Fifty-nine eyes were placed in the pNFE group and 58 eyes in the non-pNFE group. The axial length of the pNFE group (26.0 ± 1.4 mm) was significantly longer than that of the non-pNFE group (24.9 ± 1.2 mm; P < 0.001). The optic disc tilt of the pNFE group (42.1 ± 16.5 pixels) was significantly greater than that of the non-pNFE group (33.2 ± 16.8 pixels; P = 0.003). CONCLUSIONS The presence of pNFE is not rare in young healthy eyes. The eyes with pNFE have longer axial lengths and greater optic disc tilt. The pNFE should be considered when the disc margin is assessed.

Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs and is considered an autoimmune disorder against melanocytes.1 In various ethnic g...

Tessellated fundus is found as common and early-phase characteristic of myopic eyes and their locations are varied among patients. However, the relationship between their locations and morphological parameters of the eyes is still unknown. The purpose is this study is to determine the locations of the tessellations in the ocular fundus of young healthy eyes, and to determine relationships between their locations and morphological parameters of the eyes. This is a prospective observational cross sectional study of 126 eyes of 126 healthy volunteers (mean age 26.0±4.1 years). The eyes were classified into eight groups based on the location of the tessellations; no tessellation, temporal, infra-temporal, inferior, nasal, peripapillary, whole retina, and unclassified tessellations. The degree of optic disc tilt was quantified using a sine curve fitting program on the optical coherence tomographic circle scan images. The correlations between each tessellation location and the axial length, area of the optic disc plus conus (AOC), and optic disc tilt were determined. Forty-four eyes were place in the no tessellation group, 12 eyes in the temporal, 21 eyes in the infra-temporal, 9 eyes in the inferior, 8 eyes in the nasal, 15 eyes in the peripapillary, 11 eyes in the whole, and 6 eyes in the unclassified groups. The differences in the axial lengths between the no tessellation group and the infra-temporal groups were significant. A significant difference was found in the AOC between the no tessellation and the inferior, infra-temporal, and peripapilalry groups. A significant difference was found in the optic disc tilt between the no tessellation and infra-temporal groups (P

To identify delayed recognition publications, or ‘Sleeping Beauties’ (SBs), that are scarcely cited in the years or decades following their publication, but then go on to become highly cited, we screened citation histories of 184,606 articles in 52 ophthalmology journals using the Science Citation Index-Expanded (Thomson Reuters). Nine articles were identified as SBs, which accounted for 0.005% of basic materials. The SBs were published in Archives of Ophthalmology (n = 3), American Journal of Ophthalmology (n = 3), Acta Ophthalmologica (n = 1), Investigative Ophthalmology and Visual Science (n = 1), and Japanese Journal of Clinical Ophthalmology (n = 1). For citation histories according to the conjuring SB from the fairy tale, the sleep duration ranged from 7 to 59 years with mean of 19.7 years, the depth of sleep as evaluated by the average citations per year during the sleeping period ranged from 0.09 to 0.82 with mean of 0.45 citations, and the awake intensity as determined by the average citations per year during the first 5 years period following awakening ranged from 3.60 to 17.80 with mean of 8.51 citations. The number of total citations up to 2010 ranged from 109 to 375 with mean of 176.3 citations. Topics of the SBs covered description of new clinical diseases including acute retinal necrosis syndrome, cancer-associated retinopathy, and polypoidal choroidal vasculopathy, correlate of central corneal thickness with intraocular pressure readings, inadvertent eyeball perforation in retrobulbar anesthesia, pharmacologic weakening of extraocular muscles, amniotic membrane graft for ocular surface reconstruction, and refractive surgery. These data provide a perspective of rare but interesting delayed citation articles in ophthalmology.

A series of the monocyclic organophosphorus compounds ([o-OC(CH3)2C6H4]PPh(CH2 Ph)X) bearing a halogen (X = F, Cl, and Br) or a tetrafluoroborate (X = BF4) were synthesized. The solid-state structures of the bromide, the tetrafluoroborate, and an analogous fluoride ([o-OC(CF3)2C6H4]PPh(CH2 Ph)F) were determined by single crystal X-ray crystallography. The geometry of the fluoride was almost an ideal trigonal bipyramid (TBP). On the other hand, the bromide and tetrafluoroborate were essentially phosphonium salts with phosphorane character to some extent for the former. In CD3 CN, the bromide, the chloride, and the tetrafluoroborate were found to exist as phosphonium salts. However, it was suggested that in CDCl3, the bromide and the chloride have structures rapidly equilibrating or averaged between the phosphorane and the phosphonium forms. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:523–530, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20717

PURPOSE To evaluate the long-term course of visual field defects after intravitreal injection of indocyanine green (ICG) during vitrectomy. METHODS Retrospective observational case series. The medical records of seven eyes of seven patients with visual field defects after the adjunctive use of ICG during macular hole surgery were studied. All of the surgeries were performed between February 2001 and January 2002. Humphrey static perimetry and best-corrected visual acuity were examined periodically, and the main outcome measure was the mean deviation (MD) determined by the Humphrey (30-2) SITA-Fast program. RESULTS All patients were observed for more than 4.5 years, for a mean of 60.7 months and a range of 54 to 66 months. The preoperative MD was -3.5 +/- 3.1 dB (mean +/- SD), and the postoperative MD was -13.3 +/- 4.9 dB at 1 year, -13.4 +/- 4.6 dB at 2 years, -16.2 +/- 5.1 dB at 3 years, and -15.6 +/- 5.1 dB at 4 years. The decrease in the mean MD between 1 and 3 years after surgery was significant (P < 0.05). Optic disk pallor in five eyes showed a decrease in the MD between 1 year and 3 years after the surgery. There was no significant difference in the postoperative best-corrected visual acuity at any time. CONCLUSIONS The visual field defect in eyes that had undergone vitrectomy with staining of the internal limiting membrane with ICG can continue to deteriorate for at least 3 years. Eyes receiving intravitreal ICG during vitrectomy should be followed for a longer period to determine the long-term effect of ICG.

Takehiro Yamashita,1 Taiji Sakamoto,1 Hiroto Terasaki,1 Minoru Tanaka,1 Yuya Kii,1 Eisuke Uchino,1 Toshio Hisatomi,2 Kumiko Nakao1 1Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; 2Department of Ophthalmology, National Hospital Organization Kyushu Medical Center, Fukuoka,Japan Aim: To determine the relationship between the axial length (AL) and the retinal thickness in the posterior pole and to the optic disc-to-fovea (ODF) angle of healthy eyes. Procedures: A prospective, observational cross-sectional study (registration number, UMIN000006040) of 64 healthy right eyes (mean age 26.0±4.5 years) was performed. The thickness of the 64 areas within the central 24° area were measured in the Spectralis spectral domain–optical coherent tomographic images obtained by posterior pole scans. Each area was 3°×3°. The ODF angle was measured in each fundus photograph. The relationships between the AL and the retinal thickness of each of the 64areas and the ODF angle were investigated by linear regression analyses. Results: The mean AL was 25.0±1.3 mm and the mean ODF angle was 17.2°±1.0°. The average retinal thickness of the four areas around the fovea was constant and not significantly correlated with the AL. However, the retinal thicknesses of 54 of the other 60 areas were significantly and negatively correlated with the AL (R=-0.25 to -0.56, P

Purpose To describe predominant retinal vasculitis in children carrying human T-cell lymphotropic virus type 1 (HTLV-1). Methods The authors examined clinical records of patients with HTLV-1–associated uveitis between 1987 and 2001 in Kagoshima University Hospital and reviewed cases of extensive, smoldering retinal vasculitis. Results Three previously healthy teenagers noted mild visual symptoms and presented with extensive sheathing of retinal vessels, complicated by mild anterior segment inflammation. The retinal vascular disease responded poorly to systemic corticosteroids, had a smoldering course with persistent sheathing of retinal vessels, and eventually resulted in diffuse chorioretinal degeneration. Results of laboratory studies were unremarkable except for the presence of serum antibodies to HTLV-1. One patient developed HTLV-1–associated myelopathy 11 years after the onset of ocular disease. Conclusions The retinal vasculitis differed from the retinal vascular changes commonly seen in HTLV-1–associated uveitis. The authors suggest a clinical disease HTLV-1–associated retinal vasculitis that affects young HTLV-1 carriers, characterized by smoldering retinal vasculitis with ultimate retinal degeneration.

The purpose of this study was to develop a method of quantifying the degree of optic disc tilt in normal eyes. This was a prospective, observational cross sectional study of 126 right eyes of 126 healthy volunteers. The optic disc tilt was determined from the circular peripapillary optical coherence tomographic (OCT) scan images. The course of the retinal pigment epithelium (RPE) layer in the peripapillary cross sectional scan images was fit to a sine wave curve, and the amplitude of the sine curve was used to reflect the degree of the optic disc tilt in the optical axis. The repeatability of the amplitude determinations was calculated. The correlation between the amplitude and the ovality ratio of the optic disc was determined. The correlation between the amplitude and the body height was also calculated. The mean amplitude was 36.6 ± 17.5 pixels, which was significantly and inversely correlated with the ovality ratio of the optic disc (R = -0.59, P < 0.001). The intra-rater and inter-rater correlation coefficients of the amplitude were significant high (P < 0.001, both). The amplitude was significantly and inversely correlated with the body height (R = -0.38, P < 0.001), but not with the axial length. In conclusion, a sine wave function can be used to describe the course of the RPE in the circumpapillary OCT images. The results indicate that the amplitude of the sine wave can be used to represent the degree of optic disc tilt. Thus, the sine wave analyses can be used as a quantifiable and repeatable method to determine the optic disc tilt.

Optical coherence tomography (OCT) has made it possible for clinicians to measure the peripapillary choroidal thickness (ppCT) noninvasively in various ocular diseases. However, the ocular factors associated with the ppCT have not been conclusively determined. The purpose of this study was to determine the relationship between the local ppCT and the axial length, optic disc tilt, and the angle of the papillo-macular position (PMP) in healthy eyes. This was a prospective, observational cross-sectional study of 119 right eyes of 119 healthy Japanese volunteers. The ppCT was manually measured at eight sectors around the optic disc using the B-scan images of the Topcon 3D OCT RNFL 3.4 mm circle scan. The trajectory of the retinal pigment epithelium in the B-scan image was fitted to a sine curve using ImageJ, and the amplitude of the sine curve was used to determine the degree of the optic disc tilt. The PMP angle was determined in the color fundus photographs. The relationships between the ppCT and the axial length, the optic disc tilt, and PMP angle were determined by Spearman and multiple correlation analyses. The mean age was 25.8 ± 3.9 years and the mean axial length was 25.5 ± 1.4 mm. The ppCT was significantly and negatively associated with the axial length (R = -0.43 to -0.24, P

An intraocular hair is a rare condition and is usually found in eyes after a penetrating injury.1982 The removal of the hair is necessary because it can induce endophthalmitis, uveitis and subseque...

PURPOSE To determine the symmetry of the retinal thicknesses (RT) between the 32 pairs of superior and inferior sectors by posterior pole asymmetrical analysis (PPAA) of the spectral-domain optical coherence tomographic (SD-OCT) images in healthy eyes. In addition, to determine their association with the position of the peak retinal nerve fiber layer (RNFL) thickness. METHODS A prospective, observational, cross-sectional study of 64 right eyes. The Spectralis SD-OCT was used to obtain the images, and the PPAA determined the RT of the 64 cells within the central 24° area. The program also compared the thicknesses of corresponding cells across the fovea-disc axis. Circular scans were used to measure the supra- and infratemporal RNFL peak angle differences (PADs). The relationships between the RT of the corresponding cells and the relationship between the differences of the RT of the corresponding cells and PAD were investigated by linear regression analysis. RESULTS The mean differences between the RT of corresponding cells ranged from 3.1 to 23.2 μm. The RT of all upper cells were significantly correlated with the RT of the corresponding lower cells (R = 0.45-0.97, P < 0.001). The coefficients of correlation between the corresponding pairs of central- and temporal-macular cells were higher than that of the peripheral and nasal-macular cells. The differences of the pairs of nasal-macular cells RT were significantly correlated with the PAD. CONCLUSIONS The symmetry of the RT between the upper and lower cells was high in the central and temporal-macular areas but not in the peripheral and nasal-macular areas. (www.umin.ac.jp/ctr number, UMIN000006040.).

PURPOSE To determine whether a second-degree polynomial equation can fit the retinal nerve fiber (RNF) and retinal artery (RA) trajectories in the posterior pole of eyes and whether the RNF and RA trajectories are correlated with the axial length of the eye. METHODS This was a prospective observational cross-sectional study of 109 right eyes of 109 healthy participants. All participants underwent axial length measurements, optical coherence tomography (OCT) to determine the peripapillary retinal nerve fiber layer (RNFL) thickness, and red-free fundus photography. The supratemporal and infratemporal peaks of the RNFL thickness were determined in the OCT RNFL circle scan images. The trajectories of the RNF passing through the peaks of the RNFL thickness were plotted in the red-free fundus photographs and were fitted to a second-degree polynomial equation (ax(2)/100 + bx + c) by ImageJ. The coefficient a represented the steepness of the trajectories. Intraclass correlation coefficient was used to measure the reliability between the raters. The relationships between the RNF or RA trajectories and the axial length were investigated using linear regression analyses. RESULTS The mean axial length was 25.5 ± 1.4 mm, and the mean RNF trajectory and the mean RA trajectory, a, were 0.472 ± 0.123 and 0.442 ± 0.109, respectively. The intrarater and interrater correlation coefficients of the RNF trajectories were 0.954 and 0.881, respectively. The RNF and RA trajectories were significantly and positively correlated with the axial length (R = 0.28, 0.33, P < 0.01). CONCLUSIONS A longer axial length is associated with narrower RNF and RA trajectories. (www.umin.ac.jp/ctr number, UMIN000006040.).

To examine in more detail the peripheral visual field loss after macular hole surgery, we reviewed a series of 38 consecutive patients (44 eyes) with idiopathic macular hole who underwent vitrectomy and fluid-gas exchange. Ten (22.7%) eyes of 9 patients developed peripheral visual field loss shortly after successful surgery. This complication was characterized by mild to moderate wedge-shaped visual field loss that predominantly affected the inferotemporal periphery. Of these 9 patients, 2 complained of peripheral visual field loss, and the 7 others remained asymptomatic. The peripheral visual field loss remained unchanged for a mean follow-up of 18.5 months, except in one case of complete recovery. The thickness of the retinal nerve fiber layer was measured postoperatively to determine whether any damage to the optic nerve head had occurred during surgery. The information obtained in this study did not provide conclusive evidence for the understanding of the pathomechanism of the macular hole surgery-associated visual field loss. Peripheral visual field defect after otherwise uneventful surgery for idiopathic macular hole is probably not uncommon. This complication is variable in its severity and is usually permanent. Whether it is caused by any surgical trauma to the optic nerve head remains to be elucidated.

Purpose: To report extensive chorioretinal atrophy during the long-term course of Vogt–Koyanagi–Harada (VKH) disease not treated properly in the initial phase. Cases: Four patients with VKH disease were examined more than 10 years after onset of the disease. Observations: They presented initially with classic features of VKH disease, except 1 patient who had developed bilateral, acute angle-closure glaucoma as the initial sign. Two patients received systemic corticosteroid therapy at the acute phase of the disease. During the follow-up of 13–34 years subsequent to onset, these patients had chronic recurrent anterior uveitis with apparently stable depigmented fundus. Eventually, they developed diffuse, extensive chorioretinal atrophy that resulted in severe visual loss. One patient had an unusual familial occurrence of the disease. Conclusions: Failure to prescribe proper corticosteroid therapy in the initial phase of VKH disease may lead to chronic recurrent uveitis. Long-standing uveitic reactions may eventually result in severe visual loss due to extensive chorioretinal degeneration.

Sorsby's fundus dystrophy (SFD) is an autosomal dominant macular dystrophy which is developed usually in the third or fourth decade of life, and is characterized by central visual loss and nyctalopia due to fundus changes of exudative or atrophic macular lesions. Its functional prognosis is usually poor because of disciform macular scars and peripheral chorioretinal atrophies. To date, five different mutations in the tissue inhibitor of the metalloproteinases-3 (TIMP3) gene have been identified in families of a wide geographic origin, all of which are missense mutations that cause replacement by cysteine of conserved amino acids in the C-terminus of exon 5 of TIMP3. We have studied two Japanese families with SFD, the first report from the Eastern world, and identified a novel 3' splice site mutation in the TIMP3 gene, namely a single base insertion at the intron 4/exon 5 junction which converts the consensus sequence CAG to CAAG in the splice acceptor site. In addition, our patients displayed a distinctive clinical expression in that they developed macular dystrophies at an approximately 30-year later age of onset and preserved functional vision until later life with essentially uninvolved peripheral retina. The present findings may provide some insight into the genotype-phenotype relationship in SFD.

Tear cytokine has a major role in various pathophysiological conditions of the ocular surface. So far, studies on tear cytokines have shown significant progress in providing an understanding of ocular surface diseases.1–3 The information that could be acquired from each subject, however, until recently has been severely hampered by limited sample volume and assay sensitivity. More importantly, it has become apparent that the relative balance between various cytokines and combinations of cytokines could be more important than absolute concentrations. Previous studies showed that the composition of basic and reflex tears was different, which made it more difficult to understand the ocular surface disorder correctly or to treat the patients suitably.4,5 Cytometric bead array (CBA) is a microparticle based flow cytometric assay that allows us to quantify multiple molecules from a very small sample.3,6,7 Using this method, we evaluated the inflammatory cytokines of basal and reflex tears from a single sample of individual eyes. Twenty three normal volunteers (11 males and 12 females, 22–44 years of age, average 28 years) were recruited for this …

To study the effects of eye closure on the balance of tear cytokines.A total of 17 healthy volunteers with normal eyes were recruited. Tears (10 microl) were collected by capillary outflow at 09:00. The right eyes were closed with cotton bandages for 3 h, then tears were collected from each eye separately. The concentrations of inflammatory cytokines, interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor (TNF)-alpha were measured by cytometric bead array.Although the concentration of each cytokine varied between eyes, the increasing ratio for 3 h showed a similar pattern in each cytokine. IL-1beta, IL-6, IL-10, IL-12p70, and TNF-alpha increased and IL-8 decreased in normal eyes. After eye closure, the increase of IL-10 significantly diminished (P=0.037); however, the other cytokines were not affected.Eye closure decreased the concentration of IL-10 in tears, which might cause a potentially pro-inflammatory status of the ocular surface.

PURPOSE We determined a significant correlation between the retinal thickness (RT) in 64 cells or sectors of the posterior pole, and the axial length (AL) and the body height (BH). METHODS A prospective, observational cross-sectional study of 64 right eyes of 64 healthy volunteers (mean age, 26.0 ± 4.5 years; range, 22-39 years). The RT within the central 24° area was measured in the Spectralis spectral domain-optical coherence tomographic (SD-OCT) images. The correlations between the RT and the AL or the BH were determined by linear regression analyses. RESULTS The mean ± SD of the AL was 25.04 ± 1.30 mm, and that of the BH was 167.2 ± 8.5 cm. The RTs of the central four cells around the fovea were not significantly correlated with the AL. The RTs of 54 cells were significantly and negatively associated with the AL (r = -0.25 to -0.56, P < 0.05). In contrast, the RTs of the central to temporal eight cells were significantly and positively correlated with the BH (r = 0.26-0.37, P < 0.05). The RTs of 56 cells were not significantly correlated with the BH. CONCLUSIONS The RT of the posterior retina, except in the fovea, decreased as AL elongated, and those of the central temporal areas were significantly correlated with the BH. Thus, the AL and BH must be considered when the RT is evaluated. The 64-sector analysis on OCT is useful to assess the detailed changes of RT affected by them. (http://www.umin.ac.jp/ctr/index.htm number, UMIN000007154.).

AIMS: To elucidate whether there exists any clinical sign characteristic of HTLV-I associated uveitis. METHODS: Fifty five patients with HTLV-I associated uveitis were reviewed. These cases had serum antibodies to HTLV-I, and any other uveitis entities were carefully excluded by means of clinical and laboratory studies. RESULTS: Eight cases (14.5%) developed vascular lesions in the retina, characterised by grey-white, granular deposits scattered on the retinal veins and/or arteries in the posterior pole. The vascular changes did not accompany any haemorrhage, sheathing, or leakage of fluorescent dye on angiograms, and the retina was otherwise unremarkable. A single or clustered form of similar materials was also found to deposit on the vitreo-retinal interface of the foveolar area. These deposits resolved in a few weeks spontaneously or in response to corticosteroids together with anterior uveal inflammation. CONCLUSION: The vascular lesions described here suggest a characteristic sign for HTLV-I associated uveitis, and it may provide, if recognised, an additional clinical marker to establish diagnosis.

PURPOSE This retrospective observational study was designed to evaluate the frequency of, and the factors associated with, optic disc swelling in Vogt-Koyanagi-Harada disease (VKH). METHODS A retrospective observational study was conducted. We analyzed 116 eyes of 58 patients with VKH. Demographic and clinical differences between patients with and without disc swelling were analyzed. RESULTS Thirty-two eyes (27.6%) of 16 VKH patients had disc swelling. The mean age of the patients with disc swelling was higher than that of those without disc swelling (58.9 vs. 41.4, P = 0.0001). The disc-macula distance to disc diameter (DM/DD) ratio of the eyes with disc swelling was higher than that of those without disc swelling (2.81 vs. 2.59, P = 0.0007). The cup to disc (C/D) ratio of the eyes with disc swelling was smaller than that of those without disc swelling (0.18 vs. 0.32, P = 0.000001). The intraocular pressure was lower (P = 0.0084), and the refractive error was larger (P = 0.019), in eyes with disc swelling than in those without. There was no significant association between the presence of disc swelling and the range of retinal detachment, cerebrospinal fluid cell count, recurrence rate of VKH, or the incidence of sunset glow fundus. Among the eyes with disc swelling, 13 eyes of 7 patients had visual field defects even after the inflammation subsided, and these patients were older, had a higher DM/DD ratio, and had a smaller C/D ratio than those without visual field defects. CONCLUSIONS The occurrence of disc swelling in VKH was significantly correlated with age and disc morphology, rather than the severity of inflammation. Some VKH patients with disc swelling develop visual field defects from optic disc involvement.

We herein report a case of cancer-associated retinopathy (CAR) associated with malignant lymphoma, beginning with uveitis and rapidly leading to blindness.A 54-year-old woman presented with a seven-day history of bilateral progressive vision loss. She had no light perception OU. She had keratic precipitates, anterior chamber cells and fine vitreous opacities OU. Fundus examination showed no signs of inflammation, but both a narrowing of the retinal arterioles and non-active diabetic retinopathy were observed. The electroretinogram was extinguished, and optical coherence tomography showed thinning of the outer retinal layer. Systemic examination revealed malignant lymphoma. Anti-recoverin antibody was detected in the patient's serum. Based on these observations, the patient was diagnosed as having CAR. She was treated with steroid pulse therapy, but her visual acuity did not improve. Although she had no light perception, her pupils showed slow and persistent constriction in reaction to strong and long light stimulation during the follow-up period.In certain circumstances CAR can progress rapidly and lead to blindness within a few days. We observed a delayed, slow, and persistent pupillary light reflex in a CAR patient with no light perception, presumably due to the intrinsic photoactivation of the melanopsin-containing retinal ganglion cells in the uninvolved inner retina.

We report a case of intraocular lymphoma that developed macular edema and cotton wool spots after treatment with intravitreal methotrexate.A 56-year-old woman presented with blurred vision OU. Twelve months prior, she had been diagnosed with primary central nervous system lymphoma. She was in remission after high-dose methotrexate therapy and whole brain radiation therapy. Fundus examination demonstrated bilateral vitreous opacities and subretinal lesions and she was diagnosed with intraocular lymphoma by vitreous biopsy. After treatment with intavitreal methotrexate the subretinal lesions disappeared, but corneal epitheliopathy, macular edema, and cotton wool spots appeared in both eyes. After stopping the intravitreal methotrexate, the corneal epitheliopathy resolved rapidly, but the macular edema and cotton-wool spots remained. These findings disappeared gradually after a posterior sub-Tenon injection of triamcinolone acetonide. Although there was no recurrence of the intraocular lymphoma for 16 months, the patient died from a relapse of the central nervous system lymphoma.The use of intravitreal methotrexate after radiation therapy may be associated with adverse events in the retina, including possible radiation retinopathy.

Optic disc swelling is a common finding associated with Vogt–Koyanagi–Harada disease (VKH); however, visual field loss from optic disc involvement is uncommon. This reports report presents recent findings regarding unusual patients with visual field defects from optic disc involvement, thus suggesting the presence of anterior ischemic optic neuropathy (AION) in the acute phase of VKH. Observational case series. A consecutive series of 52 patients with VKH (6 complete VKH, 46 incomplete VKH) was reviewed. Fifteen patients in this series had optic disc swelling, and six of them developed irreversible visual field defects in the acute phase of VKH. The clinical features of these six patients were analyzed. The patients with associated visual field loss were four males and two females between 54 to 79 years of age. They had bilateral panuveitis associated with meningismus. All of the patients had bilateral optic disc swelling and fluorescein angiography showed both a filling delay and late leakage of the optic disc. Visual field examinations revealed various degrees of visual field defects in 11 eyes. They were treated with high-dose corticosteroid therapy, and several weeks later, both the uveal inflammation and optic disc swelling disappeared. The visual fields showed some improvement as the retinal detachments and disc swelling resolved, but the visual field defects remained in ten eyes. The small and localized visual field defects were asymptomatic. Subsequently, optic disc pallor developed in nine eyes and retinal nerve fiber layer thickness, measured by optical coherence tomography, was decreased in six eyes. The fundus gradually showed various degrees of hypopigmentation, but did not show any chorioretinal atrophy causing visual field loss. Four patients had risk factors for AION, including diabetes mellitus or a relatively small optic nerve head. In this consecutive series of patients with VKH, 15 out of 52 patients were found to have disc swelling, and six patients, who were mostly elderly, had associated visual field loss, which is probably due to AION associated with VKH.

Objective To investigate the association of endothelial nitric oxide synthase (NOS), inducible NOS, manganese superoxide dismutase (SOD), and extracellular SOD gene polymorphisms with susceptibility to Behcet disease (BD) in Japan. Methods Seventy-eight consecutive Japanese patients with BD and 107 healthy control subjects were genotyped by polymerase chain reaction or polymerase chain reaction–restriction fragment length polymorphism methods for endothelial NOS polymorphisms in intron 4, exon 7, and promoter region; inducible NOS polymorphisms in exon 16 and promoter region; manganese SOD Ala16Val polymorphism;and extracellular SOD Arg213Gly polymorphism. HLA-B*51 alleles,which have been found to be associated with BD, were also determined. Results The frequencies of manganese SOD Val16 increased significantly in patients with BD. The manganese SOD- Val/Val genotype and HLA-B*5101 had a synergistic role in controlling susceptibility to BD. There was no significant difference in the frequencies of endothelial NOS, inducible NOS, and extracellular SOD gene polymorphisms between patients with BD and control subjects. Conclusion The manganese SOD Val16 allele is associated with the development of BD in Japan. Extracellular SOD, endothelial NOS, and inducible NOS gene polymorphisms do not constitute a risk factor for developing BD in Japan. Clinical Relevance The manganese SOD gene polymorphism seems to contribute to BD.

To report on conjunctival nodules as an unusual manifestation of Vogt-Koyanagi-Harada disease.A 24-year-old woman presented with a two-month history of bilateral conjunctival injection and gradually decreased vision. Ophthalmological examinations revealed bilateral granulomatous uveitis and bulbar conjunctival nodules, and a biopsy of the conjunctival nodules was performed.The biopsy specimens showed noncaseating granulomas. The major components of the infiltrating lymphocytes were CD8-positive T cells. Topical corticosteroid therapy reduced the anterior segment inflammation, and the conjunctival nodules disappeared within a week. Afterwards, the patient demonstrated bilateral retinal detachments, sunset glow fundus and alopecia, and, therefore, was diagnosed to have Vogt-Koyanagi-Harada disease four months after the first symptoms.Conjunctival nodules may represent the primary manifestation of Vogt-Koyanagi-Harada disease.

Although optic disc swelling is one of the common findings of Vogt-Koyanagi-Harada (VKH) disease, severe visual field loss from optic disc involvement is not common. We report a case of severe visual field contraction from optic disc involvement in VKH disease.A 51-year-old woman was diagnosed as having VKH disease and was treated with intravenous pulse methylprednisolone. Exudative retinal detachments disappeared and visual acuity improved, but optic disc swelling was persistent in both eyes. Ten weeks after VKH disease onset, she claimed acute visual field loss in the right eye. Marked optic disc swelling with peripapillary hemorrhages and severe visual field loss were observed in the right eye. Fluorescein angiography showed filling delay and late leakage of the optic disc in the right eye. One month later, right optic disc swelling disappeared, but visual field loss remained. In addition, 5.5 months later, the left optic disc swelled further, and the left visual field was markedly contracted. Hyperbaric oxygen therapy was added. The swelling in the left optic disc gradually decreased and disappeared in one month, but the visual field loss remained.The optic disc involvement with irreversible visual field loss in this case is thought to be due to anterior ischemic optic neuropathy, which may be a possible complication of VKH disease.

Purpose To study the vitreomacular adhesion and the contractile force of posterior hyaloid, which are shown in triamcinolone acetonide (TA)-assisted pars plana vitrectomy (PPV). Design Interventional case series. Methods Twenty-eight eyes with diabetic macular edema (DME) without posterior vitreous detachment (PVD) received TA-assisted PPV. Surgical PVD was performed by an aspiration of vitrectomy probe, and the dynamic changes of posterior vitreous cortex and residual vitreous cortex were evaluated. Results A premacular defect was formed in the detached posterior vitreous cortex during surgical PVD in 27 of 28 eyes. Immediately thereafter, the small defect expanded into a large hole in the detached posterior vitreous cortex in all cases. A residual vitreous cortex was left on the macula in 22 eyes. Conclusions These observations demonstrate a firm vitreoretinal adhesion in the central macula and suggest that the enlargement of the defect of posterior vitreous cortex may be extrusion of vitreous out through the premacular dehiscence into the preretinal space, or a tangentially contractile force may exist in the posterior vitreous cortex. Both macular adhesion and the traction of vitreous cortex might contribute to the pathogenesis of DME and other vitreomacular disease.

Purpose: To investigate the immunogenetic background of human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis (HAU) that presents immune-mediated reactive changes in the uvea. Methods: HLA class I and class II genes were studied in 51 patients with HAU, 192 asymptomatic HTLV-1 carriers, and 266 HTLV-1-seronegative controls using a high-resolution method of HLA DNA typing. The HLA alleles of HAU were compared with those of HTLV-1 carriers and healthy controls. Results: We identified 62 distinct alleles of HLA-A, HLA-Cw, and HLA-B and 49 distinct alleles of HLA-DRB1 and HLA-DQB1 in patients with HAU, asymptomatic HTLV-1 carriers, and healthy controls. The relative frequencies of these HLA alleles did not differ among the three groups. Conclusion: The results suggest that HLA class I and class II genes do not contribute to susceptibility to HAU.

PURPOSE: To report a novel mutation of the CYP1B1 gene in a Japanese patient with primary infantile glaucoma. METHODS: DNA was extracted from leukocytes of six unrelated patients with primary infantile glaucoma. The coding regions of the CYP1B1 gene were amplified by polymerase chain reaction, examined by agarose gel separation and heteroduplex methods, and directly sequenced. RESULTS: One of the patients with primary infantile glaucoma had a mutation of the CYP1B1 gene, with an abnormal shift in agarose gel separation and heteroduplex analysis. Direct sequencing disclosed a homozygous insertion of guanine at nucleotide 1620 of exon 3, which produced a frameshift leading to premature termination of amino acid translation. The patient was male and had sporadic, classic primary infantile glaucoma. None of the other five patients with infantile glaucoma, the 30 patients with primary adult-onset glaucoma, or the 70 healthy control subjects showed any abnormalities in the CYP1B1 gene. CONCLUSIONS: This is the first report of CYP1B1 gene mutation in primary infantile glaucoma from the Eastern world. CYP1B1 gene mutation for primary infantile glaucoma spreads worldwide, but its prevalence may have ethnic or geographic differences.

Purpose: To further understand postoperative complications after vortex vein damage during scleral buckling surgery. Methods: The records of 34 patients (34 eyes) with vortex vein damage during scleral buckling surgery for rhegmatogenous retinal detachment were reviewed and compared with the records of 410 eyes undergoing similar surgery without vortex vein damage. Results: Postoperative complications were noted in 16 eyes (47%) of the damaged vortex vein group. The incidence of choroidal detachment, vitreous opacities, intraocular pressure elevation, and vitreous hemorrhage were 27%, 18%, 9%, and 6%, respectively, with a higher incidence than in the group without vortex vein damage. Other complications included development of epiretinal membrane (9%), subretinal hemorrhage (3%), and anterior segment ischemia (3%). Serous choroidal detachment occurred in the early postoperative days and subsided within 3 weeks. Vitreous opacification became marked in the later periods and continued for 2 months or longer. The incidence of postoperative choroidal detachment in the vortex vein damage group was related to the patient’s age ( P = .002) and the cutting of the vortex veins ( P = .048), but was not related to preoperative conditions of retinal detachment or the number of vortex veins damaged. All the eyes except one achieved retinal reattachment after initial surgery. Conclusions: Choroidal detachment and vitreous opacity are common after scleral buckling surgery with vortex vein damage. Although intervention of the vortex veins during scleral buckling surgery is acceptable when performing otherwise difficult to achieve ample scleral indentation, it should be minimized to avoid increased incidence of postoperative complications.

Tiny, gray-white, spherical deposits were found on the retinal vessels and vitreoretinal interface of the fovea in a 55-year-old woman with acute retinal necrosis due to varicella-zoster virus, and in a 47-year-old man with preproliferative diabetic retinopathy. Both patients developed massive vitreous opacities due to uveal inflammation or hemorrhages that rendered the fundus difficult to visualize. A therapeutic vitrectomy revealed gray-white, tiny spherical deposits, about blood-vessel-diameter, which were scattered on seemingly intact retinal arteries and veins in the posterior fundus and over the vitreoretinal interface overlying the fovea. The deposits were loosely adherent to vessel walls and were easily aspirated, and the residual materials resolved in the early postoperative days. These characteristic retinal vascular deposits resembled those seen in patients with HTLV-I associated uveitis. The two patients reported herein were otherwise asymptomatic carriers of HTLV-I. The findings provide additional information about the etiological role of HTLV-I in the development of characteristic retinal vascular deposition, although its pathogenesis remains to be elucidated.

PURPOSE We determined the relationship between the position of the peak of the retinal nerve fiber layer (RNFL) thickness, and the retinal arteries, axial length (AL), and sectoral RNFL thickness in healthy eyes. METHODS A prospective, observational cross-sectional study (registration number, UMIN000006040) of 50 healthy right eyes (mean age 25.8 ± 3.7 years) was performed. The RNFL thickness was measured by optical coherence tomography in twelve 30° sectors (clock hours) around the optic disc. The RNFL nasal-superior-temporal-inferior-nasal curves and fundus photographs were used to measure the angles between the supratemporal and infratemporal peak RNFL positions (peak angle), and the retinal artery angle (artery angle), respectively. The relationships between the peak angle, artery angle, AL, and sectoral RNFL thickness were investigated by linear regression analyses. RESULTS The peak angles were highly correlated with the artery angle (r = 0.92, P < 0.001) and correlated negatively with the AL (r = -0.49, -0.38; P < 0.01). After excluding the effect of the AL, the peak and artery angles were correlated significantly with the sectoral RNFL thickness in 8 sectors. After excluding the effect of the peak angle, the AL was correlated significantly with the sectoral RNFL thicknesses in only one sector. CONCLUSIONS The temporal RNFL thickness increased as the superior and inferior RNFL peaks, and retinal arteries shifted toward the fovea, whereas an inverse relationship was observed for the inferior and supranasal areas. The sectoral RNFL thickness is correlated better with the peak and artery angles than the axial length. (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary &recptno=R000007154&language=J number, UMIN000006040.).

The prevalence of human T cell lymphoma virus type 1 (HTLV-I) was studied among patients with endogenous uveitis. Twelve (15.8%) of 76 uveitis patients with known aetiology or clinical entity were seropositive, the prevalence being comparable with that in the general population of the southwestern area of Japan where HTLV-I is highly endemic. In the comparison, 32 (41.0%) of 78 patients with aetiology or entity undefined uveitis were seropositive for HTLV-I, which indicated a significantly higher seroprevalence than controls matched for sex and age. The 32 cases of clinical entity undefined, HTLV-I positive uveitis were characterised by acute granulomatous or non-granulomatous uveal reactions which were accompanied by vitreous opacities and retinal vasculitis. The uveal inflammatory and retinal vascular changes responded well to topical and/or systemic corticosteroids and resolved in a few weeks in the majority of cases with favourable visual outcome. The disease affected one or both eyes, and eight cases (25%) showed recurrence within a year. The general condition of the patients remained well otherwise during a follow up study (mean follow up time 15.4 months), except for three cases with a possible association of hyperthyroidism. These findings provide additional information favouring an association between HTLV-I and isolated uveitis, a new disease entity which should be termed HTLV-I-associated uveitis.

We screened 32 ophthalmology journals that had published articles during the period from 1850 through 1949 to identify top-cited articles in the field of ophthalmology (hereafter referred to as citation classics) using the online database Science Citation Index Expanded (Thompson Reuters, Chicago, Illinois). The 101 most frequently cited articles were published in 16 journals. Archives of Ophthalmology had the most top-cited articles (n = 31), followed by American Journal of Ophthalmology (n = 24) and Albrecht von Graefe's Archiv für Ophthalmologie (n = 9). These articles originated from 14 countries, with the United States publishing the majority (n = 58). Most of the citation classics are clinical studies on topics such as rubella cataract, retinopathy of prematurity, keratoconjunctivitis sicca, sympathetic ophthalmia, and the first report of eponymous diseases (eg, Leber hereditary optic neuropathy, Duane retraction syndrome, and Stargardt disease). A considerable number of these articles were ignored initially and for several decades after publication, but, like the classic fairy tale Sleeping Beauty, they have been rediscovered. Our study provides a historical perspective on the classic papers in the literature that are still influential in ophthalmology.

Human T-lymphotropic virus type 1 (HTLV-I) has been shown to spread worldwide and to be responsible for distinct systemic diseases, namely adult T-cell leukaemia and HTLV-I-associated myelopathy. Immune-mediated, inflammatory lesions in the lungs, joints, and lacrimal glands (Sjogren's syndrome) are also suggested to be associated with the retrovirus. We studied seroprevalence of antibodies to HTLV-I in patients with various ocular disorders who are residents of south-west Japan, one of the endemic areas of HTLV-I. Of 310 patients with ocular disease 72 (23.2%) were seropositive. This seroprevalence did not differ significantly from that of the general population of the area. As regards individual ocular diseases, aetiologically undefined nonspecific uveitis showed a significantly high seropositivity for HTLV-I. Of 44 patients 18 (40.9%) were seropositive. Their clinical features were acute or subacute, transient and sometimes recurrent, and granulomatous changes in the anterior uvea. Patients with isolated cotton-wool spot of the retina, non-familial retinitis pigmentosa, or keratoconjunctivitis sicca did not show any significantly high prevalence of HTLV-I infection.

We screened 46 ophthalmology journals to identify the most frequently cited articles using the Science Citation Index Expanded (1975 to 2006). The 100 most-cited articles were published in 13 journals, most in the Archives of Ophthalmology (n = 30), followed by Ophthalmology (n = 27) and the American Journal of Ophthalmology (n = 11), and originated from 10 countries, led by the United States (n = 86). The topics covered by these classic articles included epidemiology of age-related macular degeneration and glaucoma, description of new diseases including cytomegalovirus retinitis, optical coherence tomography, hypotensive medications in glaucoma, laser photocoagulation to treat diabetic retinopathy and subfoveal choroidal neovascularization, photorefractive surgery, and vitrectomy to treat idiopathic macular hole. The most frequently cited articles provide a historical perspective in the scientific advancement of ophthalmology during the last 3 decades.