Background factors determining the time to intraocular lens dislocation.

PURPOSE: To clarify the characteristics of intraocular lens (IOL) dislocation requiring IOL suture or intraocular scleral fixation. METHODS: This retrospective consecutive case series included 21 eyes (21 patients) who required sutured or sutureless intrascleral IOL fixation following IOL extraction owing to IOL dislocation at the outpatient clinic in the Department of Ophthalmology, Saitama Red Cross Hospital, Japan, between January and December 2019. Medical records were retrospectively reviewed for background diseases, location of the dislocated IOL (intracapsular/extracapsular), insertion of a capsular tension ring (CTR), and the period from IOL insertion to dislocation. RESULTS: We included 21 eyes of 21 patients who required IOL suture or intrascleral fixation for IOL dislocation at our clinic from January to December 2019 were included. The most common background disease was pseudoexfoliation syndrome (four cases), followed by atopic dermatitis, dysplasia/dehiscence of the zonule, post-retinal detachment surgery, high myopia, and uveitis (three cases each). At the time of dislocation, the IOLs were either intracapsular (16 cases, including 3 cases with CTR insertion) or extracapsular (5 cases). The time from IOL insertion to IOL dislocation was 13.7 ± 8.1 years (maximum: 31.3 years, minimum: 1.7 years). CONCLUSIONS: In this study, all 21 cases represented late IOL dislocations occurring after 3 months postoperatively. Among these late IOL dislocation cases, IOL dislocation occurred in a short-medium period of time, especially in those with CTR insertion and weakness/dehiscence of the zonule, with an average of 3 to 5 years postoperatively. We propose referring to these cases as intermediate-term IOL dislocation.

Diagnosis of cytomegalovirus corneal endotheliitis using surgically removed Descemet's membrane and endothelium despite negative results with aqueous humor PCR: a case report.

BACKGROUND: Cytomegalovirus (CMV) has been known to cause unilateral corneal endotheliitis with keratic precipitates and localized corneal edema, iridocyclitis, and secondary glaucoma. CMV endotheliitis is diagnosed based on clinical manifestations and viral examination using qualitative polymerase chain reaction (PCR) of the aqueous humor. CASE PRESENTATION: An 80-year-old woman was referred to our department for bullous keratopathy. Pigmented keratic precipitates were found in the right eye without significant anterior chamber inflammation. After 8 months there was inflammation relapse with mutton fat keratic precipitates and PCR on aqueous humor was performed, with negative results for CMV, herpes simplex virus, and varicella zoster virus. Keratic precipitates disappeared with steroid instillation, and Descemet-stripping automated endothelial keratoplasty (DSAEK) was performed for the right eye. CMV-DNA was positive at 6.0 × 102 copies/ GAPDH 105 copies in real time PCR of corneal endothelial specimen removed during DSAEK with negative results for all the other human herpes viruses. After diagnosis of CMV corneal endotheliitis, treatment with systemic and topical ganciclovir was initiated and there was resolution of symptoms. No recurrence of iridocyclitis or corneal endotheliitis was observed at 6 months follow up. CONCLUSIONS: This case report suggests that PCR should be performed using the endothelium removed during DSAEK for bullous keratopathy of an unknown cause, even if PCR for aqueous humor yields negative results.

Incidence and changing patterns of uveitis in Central Tokyo.

PURPOSE: The patterns of uveitis in Tokyo have recently changed due to advances in examination tools. We aimed to investigate the changes in the patterns of uveitis between 2004-2015 and 2016-2018. METHODS: We retrospectively reviewed the data of 732 patients who visited the Uveitis Clinic at the University of Tokyo Hospital between January 2016 and December 2018. Background characteristics, laboratory results, and imaging findings were analysed. We compared the incidences of uveitis in 2016-2018 and 2004-2015 to identify changes in the patterns. RESULTS: The most frequent diagnoses were sarcoidosis (8.9%), herpetic iridocyclitis (6.7%), intraocular lymphoma (5.5%), Vogt-Koyanagi-Harada disease (4.8%), unclassified acute anterior uveitis (4.6%), Behçet's disease (4.5%), bacterial endophthalmitis (2.9%), and Posner-Schlossman syndrome (2.6%). Suspected sarcoidosis (20.9%) was the most common cause of unclassified uveitis. The incidence of intraocular lymphoma was significantly higher in 2016-2018 than in 2004-2015. Between 2004 and 2018, herpetic iridocyclitis, bacterial endophthalmitis, and juvenile chronic iridocyclitis exhibited an increasing trend, and the incidences of Posner-Schlossman syndrome, unclassified acute anterior uveitis, Behçet's disease, and Vogt-Koyanagi-Harada disease exhibited a decreasing trend. CONCLUSION: The changing patterns of uveitis were characterised by increases in the incidence of intraocular lymphoma. This may be attributed to recent advances in examination tools, the changes in the referred patient population, and the aging Japanese population.

Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.

Epidemiology of uveitis (2013-2015) and changes in the patterns of uveitis (2004-2015) in the central Tokyo area: a retrospective study.

BACKGROUND: The distribution of uveitis varies with genetic, ethnic, geographic, environmental, and lifestyle factors. Epidemiological information about the patterns of uveitis is useful when an ophthalmologist considers the diagnosis of uveitis. Therefore, it is important to identify the causes of uveitis over the years in different regions. The purposes of this study were to characterize the uveitis patients who first arrived at the University of Tokyo Hospital in 2013-2015, and to analyze the changes in the patterns of uveitis from 2004 to 2012 to 2013-2015. METHODS: We retrospectively identified 750 newly arrived patients with uveitis who visited the Uveitis Clinic in the University of Tokyo Hospital between January 2013 and December 2015, using clinical records. We extracted data on patient age, sex, diagnosis, anatomic location of inflammation, laboratory test results of blood and urine, and chest X-ray and fluorescein fundus angiography findings for each patient. In addition, we compared these data with those from 2004 to 2012 to analyze the changes in the patterns of uveitis. RESULTS: A definite diagnosis was established in 445 patients (59.3%). The most common diagnoses were herpetic iridocyclitis (7.5%), sarcoidosis (6.1%), Behçet's disease (4.4%), Vogt-Koyanagi-Harada disease (4.1%), and intraocular lymphoma (4.1%). The most frequent unclassified type of uveitis was suspected sarcoidosis (22.3%). Analysis of the changes in the patterns of uveitis in the central Tokyo area from 2004 to 2012 to 2013-2015 revealed notable increasing trends of herpetic iridocyclitis and intraocular lymphoma, and increasing trends of bacterial endophthalmitis, fungal endophthalmitis, and juvenile chronic iridocyclitis. In contrast, the frequency of sarcoidosis, Behçet's disease, and Vogt-Koyanagi-Harada disease decreased. CONCLUSIONS: The patterns of uveitis changed considerably from 2004 to 2012 to 2013-2015. Continuous investigations about the epidemiology of uveitis are needed to diagnose uveitis more accurately.

Monoclonal immunoglobulin heavy chain gene rearrangement in Fuchs' uveitis.

BACKGROUND: Fuchs' uveitis (FU) is occasionarlly complicated with heavy vitreous opacity. We have performed vitrectomy procedures to remove vitreous opacity in affected patients as part of differential diagnosis for primary vitreoretinal lymphoma (PVRL). CASE PRESENTATION: We retrospectively reviewed the clinical records of five patients who first visited the Uveitis Clinic of the University of Tokyo Hospital between 2009 and 2013, were diagnosed with FU and underwent a vitrectomy for removal of dense vitreous opacity. All were diagnosed as FU by ocular findings and elevation of Goldmann-Witmer coefficient (GWC) value for the rubella virus (RV) antibody. In examinations of the vitreous body, cytological diagnosis, elevation of IL-10/IL-6 ratio, and the kappa/lambda ratio in flow cytometry findings were negative in all cases, whereas monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was positive in 4 cases and negative in 1 case. CONCLUSIONS: Although monoclonal IgH gene rearrangement is thought to be a reliable biomarker for PVRL, a high percentage of vitreous specimens from our FU patients showed pseudo-positive results. Ophthalmologists must take care regarding possible pseudo-positive findings when performing differential diagnosis between FU and PVRL. Combinations of results of cytological diagnosis, IL-10/IL-6 ratio, kappa/lambda ratio, and IgH gene rearrangement may be necessary for a definitive diagnosis of PVRL and differentiation from FU.

Clinical features of psoriatic uveitis in Japanese patients.

PURPOSE: To investigate the clinical features of psoriatic uveitis in Japanese patients. METHODS: Clinical features of 13 consecutive patients with psoriatic uveitis treated at our facility were retrospectively examined using medical records. In this study, we collected data about psoriasis type, uveitis laterality, onset type, HLA types, visual acuity, ocular inflammation localization, anterior segment findings, funduscopy findings, complications, recurrence, and medical treatments for uveitis and skin diseases. RESULTS: The cohort comprised ten males and three females (43.6 ± 7.1 years old), and types of psoriasis included psoriasis vulgaris (seven cases), psoriatic arthritis (four cases), pustular psoriasis (three cases) and psoriatic erythroderma (one case). Two cases represented complicated cases of pustular psoriasis and psoriatic arthritis. Seven cases were unilateral, and six cases were bilateral. All cases had acute non-granulomatous anterior uveitis, whereas panuveitis occurred in one case. Furthermore, macular edema and vascular leakage on fluorescein angiography occurred in four cases, and hyperemic disc occurred in two cases. Recurrence occurred in nine cases. In addition to topical corticosteroid treatment, eight cases underwent oral immunosuppressive treatment or biologics. All six cases undergoing HLA typing were HLA-A2 positive. CONCLUSIONS: Cases of psoriatic uveitis in Japan appear to present with acute non-granulomatous uveitis; other symptoms may include macular edema, retinal vasculitis, or hyperemic disc.

Effects of Japanese herbal medicine Sairei-to on murine experimental autoimmune uveitis.

PURPOSE: It has been suggested thatSairei-to (TJ114), a traditional Japanese herbal medicine, has immunomodulatory activities. To evaluate the effects of TJ114 on uveitis, we examined the effectiveness of oral administration in a murine model of experimental autoimmune uveitis (EAU). METHODS: Murine EAU was induced by subcutaneous injection of human inter-photoreceptor retinoid-binding protein (IRBP) peptide mixed with complete Freund's adjuvant. In the TJ114-treated group, 2 g/kg was administrated orally from 0 to 20 days after immunization. Clinical scoring, histopathological scoring of EAU, cell proliferation, cytokine assessment, and adoptive transfer experiment of splenic T cells into naïve mice were performed. RESULTS: EAU development occurred in 32 of 38 mice (86 %) in the untreated group and 12 of 33 (36 %) in the TJ114-treated group. The clinical scores for EAU in the vehicle-treated and TJ114-treated groups were 1.56 ± 1.65 and 0.59 ± 0.63 respectively, at 14 days after immunization (p < 0.01, Mann-Whitney U-test), and 2.26 ± 1.56 and 0.75 ± 1.31 respectively at 21 days (p < 0.001, Mann-Whitney U-test), while the histopathological scores at 21 days were 1.47 ± 1.42 and 0.54 ± 0.84 respectively (p < 0.01, Mann-Whitney U-test). Interferon (IFN)-γ and tumor necrosis factor (TNF)-α production by cervical lymph node cells obtained from the TJ114-treated group were significantly reduced as compared with those from the vehicle-treated group (p < 0.01, Student's unpaired t-test). Moreover, the levels of C-C motif chemokine 2 (CCL2) and IFN-γ were significantly reduced in splenocytes of TJ114-treated mice as compared with the vehicle-treated group (p < 0.01, Student's unpaired t-test). Mice that received adoptive transfer of splenic T cells from TJ114-treated EAU mice caused significantly lower severity of EAU compared to those that received from vehicle-treated EAU mice. CONCLUSION: Oral administration of TJ114 has an inhibitory effect on a murine model of EAU, possibly via reduction in cytokine production by helper type-1 T cells.

METTL23 mutation alters histone H3R17 methylation in normal-tension glaucoma.

Normal-tension glaucoma (NTG) is a heterogeneous disease characterized by retinal ganglion cell (RGC) death leading to cupping of the optic nerve head and visual field loss at normal intraocular pressure (IOP). The pathogenesis of NTG remains unclear. Here, we describe a single nucleotide mutation in exon 2 of the methyltransferase-like 23 (METTL23) gene identified in 3 generations of a Japanese family with NTG. This mutation caused METTL23 mRNA aberrant splicing, which abolished normal protein production and altered subcellular localization. Mettl23-knock-in (Mettl23+/G and Mettl23G/G) and -knockout (Mettl23+/- and Mettl23-/-) mice developed a glaucoma phenotype without elevated IOP. METTL23 is a histone arginine methyltransferase expressed in murine and macaque RGCs. However, the novel mutation reduced METTL23 expression in RGCs of Mettl23G/G mice, which recapitulated both clinical and biological phenotypes. Moreover, our findings demonstrated that METTL23 catalyzed the dimethylation of H3R17 in the retina and was required for the transcription of pS2, an estrogen receptor α target gene that was critical for RGC homeostasis through the negative regulation of NF-κB-mediated TNF-α and IL-1ß feedback. These findings suggest an etiologic role of METTL23 in NTG with tissue-specific pathology.

Genetic variants associated with glaucomatous visual field loss in primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is characterized by a progressive optic neuropathy with visual field loss. To investigate the genetic variants associated with visual field loss in POAG, Japanese POAG patients (n = 426) and control subjects (n = 246) were genotyped for 22 genetic variants predisposing to POAG that can be classified into those associated with intraocular pressure (IOP) elevation (IOP-related genetic variants) and optic nerve vulnerability independent of IOP (optic nerve-related genetic variants). The genetic risk score (GRS) of the 17 IOP-related and five optic nerve-related genetic variants was calculated, and the associations between the GRS and the mean deviation (MD) of automated static perimetry as an indicator of the severity of visual field loss and pattern standard deviation (PSD) as an indicator of the focal disturbance were evaluated. There was a significant association (Beta = - 0.51, P = 0.0012) between the IOP-related GRS and MD. The severity of visual field loss may depend on the magnitude of IOP elevation induced by additive effects of IOP-related genetic variants. A significant association (n = 135, Beta = 0.65, P = 0.0097) was found between the optic nerve-related, but not IOP-related, GRS and PSD. The optic nerve-related (optic nerve vulnerability) and IOP-related (IOP elevation) genetic variants may play an important role in the focal and diffuse visual field loss respectively. To our knowledge, this is the first report to show an association between additive effects of genetic variants predisposing to POAG and glaucomatous visual field loss, including severity and focal/diffuse disturbance of visual field loss, in POAG.

Fluorescein Angiography Scoring System Using Ultra-Wide-Field Fluorescein Angiography Versus Standard Fluorescein Angiography in Patients with Sarcoid Uveitis.

Purpose: To compare standard fluorescein angiography (FA) and ultra-wide-field (UWF) FA in evaluating sarcoid uveitis activity using the scoring system adopted by the Angiography Scoring for Uveitis Working Group (ASUWG).Methods: Standard and UWF FA images of 36 eyes with sarcoid uveitis were acquired on the same day. Three graders independently graded 72 FA images using the ASUWG scoring system. We evaluated inter-observer variability using the intra-class correlation coefficient (ICC) and compared scores of each angiographic sign.Results: The ICC was 0.77 for standard FA and 0.87 for UWF FA, with respective total scores of 12.0 and 14.6. UWF FA had higher scores than standard FA for optic disc hyperfluorescence, posterior retinal vascular staining and/or leakage, and peripheral capillary leakage.Conclusions: The scores for UWF FA had a higher ICC than those for standard FA in evaluating sarcoid uveitis. Peripheral capillary leakage scores were particularly high for UWF FA.

Genetic association of HLA-A*2601 with ocular Behçet's disease in Japanese patients.

OBJECTIVES: Behçet's disease (BD) is known to be associated with HLA-B*51, especially HLA-B*5101, in many different ethnic groups. Recently, several HLA-A or -B alleles have been proposed as possible candidate genes for BD in addition to HLA-B*5101. To investigate those associations, we studied HLA-A and -B alleles in Japanese ocular BD patients and the association of possible susceptibility HLA genes with visual prognosis. METHODS: Eighty-eight Japanese BD patients with uveitis and 104 healthy controls were enrolled for analyses of HLA-A and B alleles. Statistical analysis was performed with Fisher's exact test and odds ratio (OR). Association of the possible susceptible HLA gene and visual prognosis was also examined. RESULTS: The phenotype frequency (PF) of HLA-A*2601 was significantly higher in the patients (37.5%) than the controls (14.4%) (pc=0.00529, OR=3.56), especially in patients without HLA-B*5101 (57.4% vs. 14.1%, pc=4.58x10-6, OR=8.21). In contrast, the PF of HLA-A*2601 was not increased in patients with HLA-B*5101 (14.6% vs. 15.8%). Also, the PF in patients possessing HLA-A*2601 or HLAB* 5101 was increased up to 77.3%. Interestingly, the PF of HLA-A*2601 was significantly associated with poor visual prognosis corresponding to visual acuity of 0.1 or less in the worse eye (p=0.0262). CONCLUSIONS: Our results indicate that HLA-A*2601 is possibly associated with ocular BD, independent of HLAB* 5101, indicating that HLA-A*2601 is an additional susceptibility allele candidate of ocular BD in Japan. HLAA* 2601 would also be a possible marker for poor visual prognosis.

Best-corrected visual acuity and frequency of ocular attacks during the initial 10 years in patients with Behçet's disease.

BACKGROUND: Recent publications have suggested considerable improvements in the clinical outcomes of ocular Behcet's disease (BD) patients. However, the long-term time course of clinical ocular features of BD in recent cases remains largely unknown. In this study, we investigated annual time-course changes of best-corrected visual acuity (BCVA) during ocular convalescent stages, as well as annual frequency of ocular attacks during the initial 10 years of follow-up in patients with BD. METHODS: We studied 75 eyes in 39 patients (31 men, eight women) with BD, who were referred to our hospital between 1980 and 1996 within 1 year after the initial ocular attack and followed them up continuously for more than 10 years. The clinical courses of BCVA at the ocular convalescent stage from the onset of ocular disease were retrospectively examined, and the numbers of ocular attacks per eye per year were determined. RESULTS: Mean BCVA was 0.59 at 1 year, 0.31 at 3 years, and 0.12 at 10 years from the onset of ocular disease, while the numbers of ocular attacks per eye were 4.1 +/- 3.1 at 1 year, 2.2 +/- 1.9 at 5 years, and 1.4 +/- 1.8 at 10 years. Ocular attacks were still observed in 33 eyes (45%) of 21 patients (54%) with BD even after 10 years. Final BCVA in 42 eyes (56%) became lower than 0.5. The major reasons for poor visual prognosis were macular atrophy (41%) and chorioretinal atrophy (26%). CONCLUSIONS: The decline of BVCA continued, and nearly half the patients still suffered from ocular attacks at 10 years after the onset of ocular BD.

Endogenous Candida albicans infection causing subretinal abscess.

PURPOSE: We report a case of Candida albicans endophthalmitis with subretinal abscess formation in a patient who underwent liver transplantation. METHODS: Case report. RESULTS: A 51-year-old Japanese woman complained of deep pain and ciliary injection in her right eye. Three months prior, the patient had undergone liver transplantation for cirrhosis caused by hepatitis C. A slit-lamp examination revealed intense anterior chamber inflammation with hypopyon and fundoscopy showed a yellowish-white subretinal mass lesion in the inferior peripheral fundus. Systemic and topical antibiotics did not prevent further progression of the infection. The patient underwent pars plana vitrectomy treatment three times and a histopathological study of a vitreous specimen revealed C. albicans to be the causative organism. CONCLUSION: A subretinal abscess, previously reported in Nocardia, Pseudomonas, Staphylococcus, and Aspergillus infection cases, can also occur in patients infected with Candida. Therefore, Candida infection should be considered as a potential cause of subretinal abscess in organ transplant recipients.

Comparisons of Clinical Features in Japanese Patients with Behçet's Uveitis Treated in the 1990s and the 2000s.

Purpose: We investigated clinical characteristics of ocular Behçet's disease (BD) patients treated in the 1990s and the 2000s.Methods: We retrospectively examined records of 68 newly arrived patients with ocular BD followed for more than 4 months during the 2000s and compared to those of 107 patients during the 1990s. Patient profiles, ocular and systemic symptoms, frequency of ocular attacks, BD ocular attack score 24-6 months (BOS24-6M), best-corrected visual acuity (BCVA), and immunomodulatory treatment were noted.Results: Clinical characteristics in the 2000s showed increases in iridocyclitis type, intestinal-, vasculo-, and neuro-BD cases, oral corticosteroid, methotrexate, and infliximab therapy usage, cataract and glaucoma surgery, and pseudophakia, and decreases in BOS24-6M and cyclophosphamide usage. BCVA of 20/30 or better at the final visit was slightly increased in the 2000s.Conclusions: Milder ocular BD tendency was seen in cases in the 2000s, whereas the incidence of special type of BD might be increasing.

Retinal vascular inflammatory and occlusive changes in infectious and non-infectious uveitis.

PURPOSE: Retinal vasculitis and occlusive changes are important signs of posterior uveitis and are possible diagnostic markers for uveitis. However, the frequency of arteritis and phlebitis in various uveitis entities, including infectious uveitis (IU) and non-infectious uveitis (NIU), have not been systematically investigated. STUDY DESIGN: Retrospective. METHODS: We investigated the frequency of retinal vascular inflammatory and occlusive changes in patients with IU and NIU. The study included 283 patients with intermediate, posterior, or pan-uveitis who were diagnosed with IU (presumed tuberculous uveitis, acute retinal necrosis, cytomegalovirus retinitis, human T-cell lymphotropic virus type 1-associated uveitis, toxoplasmic retinitis, syphilitic uveitis, rubella virus-associated uveitis, fungal endophthalmitis, and bacterial endophthalmitis) or NIU (sarcoidosis, Behçet's disease, Vogt-Koyanagi-Harada disease, human leukocyte antigen-B27-associated uveitis, systemic lupus erythematosus retinopathy, psoriatic uveitis, rheumatoid arthritis/collagen disease-associated uveitis, multiple sclerosis-associated uveitis, and sympathetic ophthalmia). All patients underwent fluorescein angiography (FA) and color photography examinations of the fundus. Presence of inflammatory and occlusive changes was determined by FA images. RESULTS: Significantly higher positive ratios of phlebitis, vein sheathing, vein occlusion, arteritis, artery sheathing, artery occlusion, and avascular areas were observed in the IU group than in the NIU group (p < 0.05). Notably, the discrepancy between IU and NIU was prominent with regard to retinal arterial changes (arteritis [57.9% vs 11.2%], inflammatory artery sheathing [33.7% vs 0%], and artery occlusion [22.1% vs 3.7%], respectively; p < 0.0001). CONCLUSION: Findings of vasculitis and occlusion, especially in retinal arteries, in FA strongly suggest an infectious origin of active uveitis.

Genetic Variants Associated With the Onset and Progression of Primary Open-Angle Glaucoma.

PURPOSE: We sought to investigate the genetic variants associated with the onset and progression of primary open-angle glaucoma (POAG). DESIGN: Case-control genetic association study. METHODS: Japanese POAG patients (n = 505) and control subjects (n = 246) were genotyped for 22 genetic variants predisposing to POAG that can be classified into those associated with intraocular pressure (IOP) elevation (IOP-related genetic variants) and optic nerve vulnerability independent of IOP (non-IOP-related genetic variants). The total number of risk alleles of the 17 IOP-related and 5 non-IOP-related genetic variants were calculated as the genetic risk score (GRS), and the associations between the GRS and family history of glaucoma as an indicator of POAG onset and age at the diagnosis of glaucoma as an indicator of POAG progression were evaluated. RESULTS: There was a significant association (P = .014; odds ratio 1.26 per GRS) between the non-IOP-related GRS, but not IOP-related GRS, and a family history of glaucoma in POAG. As the non-IOP-related GRS increased, the risk of a family history of glaucoma increased. In contrast, a significant association (P = .0014; ß = -0.14) was found between the IOP-related GRS, but not non-IOP-related GRS, and age at the diagnosis of glaucoma. As the IOP-related GRS increased, age at the diagnosis of glaucoma decreased. CONCLUSION: The results indicate that non-IOP-related (optic nerve vulnerability) rather than IOP-related (IOP elevation) genetic variants may play an important role in the onset of POAG (family history of glaucoma) and that IOP-related rather than non-IOP-related genetic variants may play an important role in its progression (age at the diagnosis of glaucoma).

Clinical characteristics and ocular complications of patients with scleritis in Japanese.

PURPOSE: To investigate the clinical characteristics of Japanese patients with scleritis STUDY DESIGN: Retrospective study METHODS: The clinical records of 123 patients with scleritis, who presented to the University of Tokyo Hospital between January, 2004 and December, 2015, were retrospectively reviewed. RESULTS: The cohort comprised 55 men and 68 women (mean age, 57.8±16.4 years), of which 76 showed anterior diffuse scleritis, 17 showed anterior nodular scleritis, 10 showed anterior necrotizing scleritis, and 20 showed posterior scleritis. The underlying etiology was identified in 39 patients. Autoimmune diseases were present in 32 patients, including eight with rheumatoid arthritis, seven with antineutrophil cytoplasmic antibody-associated vascular disease, and six with relapsing polychondritis. Ocular hypertension was the most common ocular complication (41%), followed by anterior chamber cells (38%). Fifty-three percent of patients required systemic immunosuppressive medication. Systemic corticosteroids were the most commonly used medication (45%), followed by methotrexate (11%). A, decrease in vision was observed in one-third of patients with anterior necrotizing scleritis or posterior scleritis, of which secondary glaucoma and optic neuritis were the major causes. CONCLUSION: Autoimmune diseases were present in 26% of patients. One-third of patients with anterior necrotizing scleritis or posterior scleritis experienced decreased vision, mostly due to secondary glaucoma and optic neuritis. Therefore, controlling intraocular pressure by methods such as administration of steroid-sparing immunosuppressive medication and appropriate treatment for posterior scleritis are essential for scleritis treatment.

Genetic Variant Near PLXDC2 Influences the Risk of Primary Open-angle Glaucoma by Increasing Intraocular Pressure in the Japanese Population.

PURPOSE: The purpose of this study is to assess the association between the genetic variants that were previously reported to be associated with primary open-angle glaucoma (POAG) in the Japanese population and the phenotypic features. METHODS: A total of 661 Japanese patients including 417 patients with POAG [normal tension glaucoma (NTG), n=210; high tension glaucoma (HTG), n=207] and 244 control subjects without glaucoma were analyzed for 3 genetic variants: rs547984 (near gene: ZP4), rs7081455 (PLXDC2), and rs7961953 (TMTC2). The allele frequency differences between POAG (NTG or HTG) patients and control subjects were estimated. The association between these genetic variants and the phenotypic features, including the maximum intraocular pressure (IOP) and the vertical cup-to-disc ratio, was evaluated. RESULTS: There was a significant difference in the rs7081455 (PLXDC2) allele frequencies between the POAG (P=0.0050) patients and the control subjects. An almost 1.5 increase in the risk of POAG (P=0.0042, odds ratio 1.52) was found with a G allele of rs7081455 (PLXDC2). The maximum IOP [23.5±10.3 mm Hg (mean±SD)] in patients with the GG genotype of rs7081455 (PLXDC2) was significantly higher (P=0.0037) than that (19.9±7.4 mm Hg) in patients with the TT genotype. CONCLUSIONS: The genetic variant near the PLXDC2 gene was found to influence the risk of POAG by increasing IOP in the Japanese population.

Frequency of Uveitis in the Central Tokyo Area (2010-2012).

PURPOSE: To investigate the frequency of conditions of newly arrived patients with uveitis from 2010 to 2012 and compare this frequency with that since 2004. METHODS: We retrospectively analyzed clinical records of patients who visited the outpatient clinic from January 2010 to December 2012, and compared them with those from 2004-2009. RESULTS: From 2010 to 2012, 695 new patients with uveitis visited Tokyo University Hospital, with a definite diagnosis made in 431 (62.0%). The most common diagnosis was scleritis (8.3%), followed by sarcoidosis (8.1%); herpetic iridocyclitis (5.5%); Behçet disease (4.6%); Vogt-Koyanagi-Harada disease (4.0%); acute anterior uveitis (3.7%); Posner-Schlossman syndrome (3.6%); intraocular malignant lymphoma (3.0%); and bacterial endophthalmitis (1.9%). The most frequent unclassified type of uveitis was sarcoidosis-suspected (14.8%). CONCLUSIONS: When compared with years 2004-2009, the present series showed an increasing trend of intraocular malignant lymphoma, bacterial endophthalmitis, and chronic iridocyclitis, and a notable increase in chronic iridocyclitis in young girls, with decreasing trends of scleritis and Vogt-Koyanagi-Harada disease.