The hypothetical molecular mechanism of the ethnic variations in the manifestation of age-related macular degeneration; focuses on the functions of the most significant susceptibility genes.

Age-related macular degeneration (AMD) is the leading sight-threatening disease in developed countries. On the other hand, recent studies indicated an ethnic variation in the phenotype of AMD. For example, several reports demonstrated that the incidence of drusen in AMD patients is less in Asians compared to Caucasians though the reason has not been clarified yet. In the last decades, several genome association studies have disclosed many susceptible genes of AMD and revealed that the association strength of some genes was different among races and AMD phenotypes. In this review article, the essential findings of the clinical studies and genome association studies for the most significant genes CFH and ARMS2/HTRA1 in AMD of different races are summarized, and theoretical hypotheses about the molecular mechanisms underlying the ethnic variation in the AMD manifestation mainly focused on those genes between Caucasians and Asians are discussed.

Artificial intelligence-based differential diagnosis of orbital MALT lymphoma and IgG4 related ophthalmic disease using hematoxylin-eosin images.

PURPOSE: To investigate the possibility of distinguishing between IgG4-related ophthalmic disease (IgG4-ROD) and orbital MALT lymphoma using artificial intelligence (AI) and hematoxylin-eosin (HE) images. METHODS: After identifying a total of 127 patients from whom we were able to procure tissue blocks with IgG4-ROD and orbital MALT lymphoma, we performed histological and molecular genetic analyses, such as gene rearrangement. Subsequently, pathological HE images were collected from these patients followed by the cutting out of 10 different image patches from the HE image of each patient. A total of 970 image patches from the 97 patients were used to construct nine different models of deep learning, and the 300 image patches from the remaining 30 patients were used to evaluate the diagnostic performance of the models. Area under the curve (AUC) and accuracy (ACC) were used for the performance evaluation of the deep learning models. In addition, four ophthalmologists performed the binary classification between IgG4-ROD and orbital MALT lymphoma. RESULTS: EVA, which is a vision-centric foundation model to explore the limits of visual representation, was the best deep learning model among the nine models. The results of EVA were ACC = 73.3% and AUC = 0.807. The ACC of the four ophthalmologists ranged from 40 to 60%. CONCLUSIONS: It was possible to construct an AI software based on deep learning that was able to distinguish between IgG4-ROD and orbital MALT. This AI model may be useful as an initial screening tool to direct further ancillary investigations.

Efficacy, durability, and safety of faricimab up to every 16 weeks in patients with neovascular age-related macular degeneration: 2-year results from the Japan subgroup of the phase III TENAYA trial.

PURPOSE: To evaluate 2-year efficacy, durability, and safety of faricimab in the TENAYA Japan subgroup and pooled global TENAYA/LUCERNE cohort of patients with neovascular age-related macular degeneration (nAMD). METHODS: Subgroup analysis of TENAYA/LUCERNE (NCT03823287/NCT03823300): phase III, multicentre, randomised, active comparator-controlled, double-masked, non-inferiority trials. Treatment-naïve patients aged ≥ 50 years with nAMD were randomised (1:1) to intravitreal faricimab (6.0 mg up to every 16 weeks [Q16W] after 4 initial Q4W doses) or aflibercept (2.0 mg Q8W after 3 initial Q4W doses). Outcomes were assessed through year 2 for the TENAYA Japan subgroup (N = 133) and global pooled TENAYA/LUCERNE cohort (N = 1329). RESULTS: Vision and anatomic improvements achieved with faricimab at year 1 were maintained over 2 years and were generally comparable between the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Adjusted mean best-corrected visual acuity (BCVA) change from baseline at year 2 for the TENAYA Japan subgroup and global pooled TENAYA/LUCERNE cohort was +7.1 (3.7-10.5) and +4.4 (3.2-5.5) letters in the faricimab arm, respectively, and +5.2 (1.9-8.6) and +4.3 (3.1-5.4) letters in the aflibercept arm, respectively. At week 112, the proportion of faricimab-treated patients on Q16W dosing was 61.0% and 63.1% in the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Faricimab was well tolerated through year 2. CONCLUSION: Year 2 TENAYA Japan subgroup findings for faricimab were generally consistent with the pooled global TENAYA/LUCERNE results in patients with nAMD. Vision and anatomical benefits with faricimab were similar to those with aflibercept but with fewer injections.

INCIDENCE AND RISK FACTORS OF INTRAOCULAR INFLAMMATION AFTER BROLUCIZUMAB TREATMENT IN JAPAN: A Multicenter Age-Related Macular Degeneration Study.

PURPOSE: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan. METHODS: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors. RESULTS: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset. CONCLUSION: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.

Genome-Wide Association Study of Age-Related Macular Degeneration Reveals 2 New Loci Implying Shared Genetic Components with Central Serous Chorioretinopathy.

PURPOSE: To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population. DESIGN: Genome-wide association study (GWAS). PARTICIPANTS: Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses. METHODS: We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants. MAIN OUTCOME MEASURES: Associations of genetic variants with AMD. RESULTS: A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P < 5.0 × 10-8). Of these loci, 4 were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2), and 2 were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all datasets, we observed strong associations in these loci (P = 1.88 × 10-12 and P = 1.35 × 10-9 for meta-analysis for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were associated significantly with CSC (P = 4.86 × 10-3 and P = 4.28 × 10-3 for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (rg [the measure of genetic correlation] = -0.33; P = 0.01; false discovery rate, 0.099). CONCLUSIONS: Our findings imply shared genetic components conferring the risk of both AMD and CSC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Genome-wide Survival Analysis for Macular Neovascularization Development in Central Serous Chorioretinopathy Revealed Shared Genetic Susceptibility with Polypoidal Choroidal Vasculopathy.

PURPOSE: To identify susceptibility genes for macular neovascularization (MNV) development in central serous chorioretinopathy (CSC). DESIGN: Genome-wide survival analysis using a longitudinal cohort study. PARTICIPANTS: We included 402 and 137 patients with CSC but without MNV at their first visit from the Kyoto CSC Cohort and Kobe CSC dataset, respectively. All patients underwent detailed ophthalmic examinations, including multimodal imaging, such as fundus autofluorescence, spectral-domain OCT, and fluorescein angiography/indocyanine green angiography or OCT angiography. METHODS: We conducted a genome-wide survival analysis using the Kyoto CSC Cohort. We applied the Cox proportional hazard model to adjust for age, sex, and the first principal component. Single nucleotide polymorphisms (SNPs) with P values < 1.0 × 10-5 were carried forward to the replication in the Kobe CSC dataset. Moreover, we evaluated the contribution of previously reported age-related macular degeneration (AMD) susceptibility loci. We used FUMA and ToppFun for the functional enrichment analysis. MAIN OUTCOME MEASURES: The association between SNPs and MNV development in patients with CSC. RESULTS: Rs370974631 near ARMS2 displayed a genome-wide significant association in the meta-analysis of discovery and replication result (hazard ratio [HR]meta, 3.63; Pmeta = 5.76 × 10-9). Among previously reported AMD susceptibility loci, we additionally identified CFH rs800292 (HR, 0.39, P = 2.55 × 10-4), COL4A3 rs4276018 (HR, 0.26, P = 1.56 × 10-3), and B3GALTL rs9564692 (HR, 0.56, P = 8.30 × 10-3) as susceptibility loci for MNV development in CSC. The functional enrichment analysis revealed significant enrichment of 8 pathways (GO:0051561, GO:0036444, GO:0008282, GO:1990246, GO:0015272, GO:0030955, GO:0031420, and GO:0005242) related to ion transport. CONCLUSIONS: ARMS2, CFH, COL4A3, and B3GALTL were identified as susceptibility genes for MNV development in CSC. These 4 genes are known as susceptibility genes for AMD, whereas COL4A3 and B3GALTL were previously reported to be polypoidal choroidal vasculopathy (PCV)-specific susceptibility genes. Our findings revealed the shared genetic susceptibility between PCV and MNV secondary to CSC.

Safety and efficacy of 27-gauge transconjunctival vitrectomy for the diagnosis of posterior uveitis or pan uveitis of unknown origin.

BACKGROUND: Diagnostic vitrectomy is an important method for evaluating uveitis, and its diagnostic utility is high regardless of whether the uveitis is infectious or non-infectious. The course of diagnostic vitreous surgery with 27-gauge pars plana vitrectomy and perioperative complications is reported. METHODS: An observational retrospective study of patients who underwent 27-gauge diagnostic vitrectomy due to atypical intraocular inflammation was conducted. The final diagnosis rate, complications due to surgery, preoperative visual acuity, and postoperative visual acuity (1 month and 6 months after surgery) were examined retrospectively. RESULTS: Diagnostic vitreous surgery was performed in 32 patients and 35 eyes (14 males and 18 females, age 14-85 years, median 67 years) during the study period. The average operation time was 52 min for 19 eyes with cataract surgery and 35 min for 16 eyes without cataract surgery. Preoperative log(minimum angle of resolution [MAR]) visual acuity was 0.84 ± 0.87, 1-month postoperative logMAR visual acuity was 0.41 ± 0.55 (p = 0.004, n = 28), and 6-month postoperative average logMAR visual acuity was 0.45 ± 0.73 (p = 0.012, n = 15). The diagnosis was made by diagnostic vitrectomy in 19 cases (54%). Postoperative complications were observed in 2 of 35 postoperative patients (5%); one involved increased intraocular pressure, and the other case involved vitreous hemorrhage of the eye, necessitating reoperation. CONCLUSION: Diagnostic 27-gauge vitrectomy could be effective for evaluating intraocular inflammation.

Pulmonary hypertension with bronchopulmonary dysplasia: Aichi cohort study.

BACKGROUND: The incidence of pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD) has not been investigated in regional cohorts. The aim of this study was to clarify the incidence of PH associated with BPD in all very low birthweight infants (VLBWIs) born during the study period in Aichi Prefecture, Japan. METHODS: We conducted a retrospective observational cohort study of all VLBWIs born in Aichi Prefecture. The inclusion criteria were VLB, birth between 1 January 2015 and 31 December 2015, and admission to any neonatal intensive care unit in Aichi Prefecture. BPD28d and BPD36w were defined as the need for supplemental oxygen or any respiratory support at 28 days of age or 36 weeks of postmenstrual age (PMA). The primary outcome was the incidence of PH after 36 weeks' PMA (PH36w) in VLBWIs with BPD28d and BPD36w. The secondary outcomes were the clinical factors related to PH36w in BPD36w patients. Mann-Whitney U-test and Fisher's exact test were used for univariate analysis. Differences were considered statistically significant at P < 0.05. Risk ratio (RR) and 95% confidence interval (CI) were also evaluated. RESULTS: A total of 441 patients were analyzed. A total of 217 and 131 patients met the definition of BPD28d and BPD36w, respectively. Nine patients were diagnosed with PH36w (4.2% and 6.9% of the BPD28d and BPD36w patients, respectively). The presence of oligohydramnios (RR, 2.71; 95% CI: 1.55-4.73, P = 0.014) and sepsis (RR, 3.62; 95% CI: 1.51-8.63, P = 0.025) was significant in the PH36w patients. CONCLUSIONS: The incidence of PH36w was 4.2% and 6.9% in the BPD28d and BPD36w patients, respectively. Oligohydramnios and sepsis were significantly associated with PH36w in VLBWIs.

Expression of thrombospondin-1 in conjunctival squamous cell carcinoma is correlated to the Ki67 index and associated with progression-free survival.

PURPOSE: Conjunctival squamous cell carcinoma (SCC) is primarily treated with surgical resection. SCC has various stages, and local recurrence is common. The purpose of this study was to investigate thrombospondin-1 expression and its association with prognosis. METHODS: In this retrospective study, a gene expression array along with immunohistochemistry were performed for the evaluation of thrombospondin-1 expression, localization, as well as Ki67 labeling cell indices in carcinoma in situ (Tis) and advanced conjunctival SCC (Tadv). The presence or absence and intensity of cytoplasmic and nuclear staining in tumor cells were also divided into groups with a score of 0-3 and semi-quantitatively analyzed to investigate intracellular staining patterns. The association between thrombospondin-1 expression and tumor progression in a series of 31 conjunctival SCCs was further investigated. RESULTS: All 31 patients in the cohort (100%) were East Asian. A simple comparison between Tis and Tadv demonstrated significant differences in expressions of 45 genes, including thrombospondin-1 (p < 0.01). In this cohort, 30/31 tumors were positive (96%) for thrombospondin-1. Furthermore, thrombospondin-1 intracellular staining pattern analysis scores were 2.12 and 0.96 for nuclear and cytoplasmic staining, respectively, with a significant difference observed between Tis and Tadv (p < 0.01). Alteration of the Ki67 labeling index was significantly correlated with that of the thrombospondin-1 cytoplasmic score (p = 0.030). Furthermore, univariate Cox regression analysis showed a significant correlation between thrombospondin-1 staining and progression-free survival (p = 0.026) and final orbital exenteration (p = 0.019). CONCLUSIONS: The present results demonstrated that thrombospondin-1 is a potential molecular target in the pathology of conjunctival SCC, in addition to serving as a prognostic factor.

Selective retina therapy (SRT) for macular serous retinal detachment associated with tilted disc syndrome.

PURPOSE: Tilted disc syndrome (TDS) may be associated with a macular serous retinal detachment (MSRD). However, ideal therapy for this complication is still unestablished yet to date. The purpose of this study is to investigate the effect of selective retina therapy (SRT) for MSRD associated with TDS. METHODS: This retrospective study included 11 eyes of 10 patients (1 male and 9 females), who were treated with SRT for MSRD associated with TDS, and observed at least 12 months after treatment. The mean age was 56 years old (range 44-66). An SRT laser (527 nm, 1.7 µs, 100 Hz; Medical Laser Center Lübeck, Germany) was used for treatment. The changes of best-corrected visual acuity (BCVA), central macular thickness (CMT), and central choroidal thickness (CCT) were examined. Subfoveal curve height (SFCH) was calculated at baseline. RESULTS: The mean follow-up period was 24.4 months (range 12-48 months). The mean BCVA (logMAR), CMT, and CCT changed from 0.03 ± 0.10, 324 ± 82 µm, and 194 ± 68 µm preoperatively to 0.07 ± 0.17, 274 ± 94 µm, and 188 ± 65 µm at final follow-up, respectively, with significant difference on CMT (BCVA: p = 0.44, CMT: p < 0.05, CCT: p = 0.21). The MSRD disappeared in 6 eyes (55%) and the average number of SRT irradiations until resolution of MSRD was 2.6 times (range 1-5 times). There was no significant association between SFCH and resolution of MSRD (p = 0.19). CONCLUSIONS: SRT may promote absorption of MSRD and maintenance of BCVA for TDS. Randomized and prospective clinical studies are needed to evaluate the effectiveness of SRT for MSRD associated with TDS.

Visual outcomes and choroidal thickness associated with human leukocyte antigen DRB1*04 in unclassifiable uveitis in Japanese patients.

PURPOSE: Human leukocyte antigen (HLA) and immunity are related. Uveitis is also closely related to immunity. For example, the common presence of human leukocyte antigen (HLA)-DRB1*04 in the immune response is well known. The aim of this study was to investigate the relationship between visual prognosis and various HLA alleles before and after therapy in patients with unclassifiable uveitis, excluding those with Vogt-Koyanagi-Harada (VKH) disease. METHODS: This retrospective case series included 42 eyes from 22 consecutive patients with unclassifiable uveitis, excluding those with VKH disease. Visual acuity (VA), sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and 6-month visits. Mean values of parameters were compared at each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primers. RESULTS: DRB1*04 showed a dominant change. No significant difference was observed in the other alleles. In DRB1*04, The mean differences in initial CCT, 6-month CCT, and 6-month VA showed statistically significant difference was found in best-corrected visual acuity (BCVA) between DRB1*04+ and DRB1*04- at the first visit. BCVA values at baseline and at the final visit were 0.13 ± 0.29 and 0.20 ± 0.36 in the DRB1*04+ and 0.00045 ± 0.20 and - 0.058 ± 0.11 in the DRB1*04- groups(p = 0.00465). Central Choroidal Thickness (CCT) values pretreatment and at the final visit after treatment were (pretreatment:361.00 ± 361.0 µm,after treatment: 286.00 ± 106.53 µm, p = 0.0174) in the DRB1*04+ group, and (pretreatment:281.3 ± 139.68 µm,after treatment:223.85 ± 99.034 µm, p = 0.0426) in the DRB1*04- group, respectively, indicating changes between baseline and the final visit. CCT was significantly greater in the DRB1*04+ group at both the initial visit and at 6 months. Multivariate analysis showed a significant difference between the presence or absence of DRB1*04 and sex. CONCLUSION: HLA-DRB1*04 allele may affect visual prognosis and CCT in unclassifiable uveitis.

CFH and VIPR2 as susceptibility loci in choroidal thickness and pachychoroid disease central serous chorioretinopathy.

Central serous chorioretinopathy (CSC) is a common disease affecting younger people and may lead to vision loss. CSC shares phenotypic overlap with age-related macular degeneration (AMD). As recent studies have revealed a characteristic increase of choroidal thickness in CSC, we conducted a genome-wide association study on choroidal thickness in 3,418 individuals followed by TaqMan assays in 2,692 subjects, and we identified two susceptibility loci: CFH rs800292, an established AMD susceptibility polymorphism, and VIPR2 rs3793217 (P = 2.05 × 10-10 and 6.75 × 10-8, respectively). Case-control studies using patients with CSC confirmed associations between both polymorphisms and CSC (P = 5.27 × 10-5 and 5.14 × 10-5, respectively). The CFH rs800292 G allele is reportedly a risk allele for AMD, whereas the A allele conferred risk for thicker choroid and CSC development. This study not only shows that susceptibility genes for CSC could be discovered using choroidal thickness as a defining variable but also, deepens the understanding of differences between CSC and AMD pathophysiology.

Genetic factors associated with treatment response to reduced-fluence photodynamic therapy for chronic central serous chorioretinopathy.

Purpose: Reduced-fluence photodynamic therapy (RFPDT) has proven effective for some patients with chronic central serous chorioretinopathy (cCSC). Several clinicodemographic factors influencing treatment response have been identified, but associations with genetic factors have not been examined. Therefore, we investigated the associations of single nucleotide polymorphisms (SNPs) implicated in cCSC pathogenesis with clinical outcome following RFPDT. Methods: This was a retrospective study of 87 eyes from 87 patients with cCSC who underwent RFPDT and were followed up for more than 12 months. Patients were divided into a good response group (53 patients) and a poor response group (34 patients) based on either persistence or recurrence of subretinal fluid detected with spectral domain optical coherence tomography after the first application of RFPDT. SNPs in the genes encoding age-related maculopathy susceptibility protein 2 (ARMS2, SNP rs10490924) and complement factor H (CFH, SNP rs800292) were genotyped using TaqMan technology. Results: There were no statistically significant differences in the baseline characteristics between the response groups except the degree of hyperfluorescence on indocyanine green angiography (ICGA; p = 0.011). The minor (T) allele frequency of ARMS2 (rs10490924) were statistically significantly lower in the good response group than in the poor response group (24.0% versus 41.0%, p = 0.021). Further, the good response frequency was statistically significantly lower in patients with at least one minor allele (GT or TT) compared to the homozygous major allele group (GG; p<0.05). The baseline best-corrected visual acuity (BCVA) at 12 months after RFPDT was statistically significantly better in the GG carriers than in the GT or TT carriers (p<0.01). Logistic regression analysis showed less intense hyperfluorescence on ICGA, and the T allele of ARMS2 (rs10490924) was statistically significantly associated with poor response to PDT treatment (p = 0.012, p = 0.039, respectively). Conclusions: Carriers of the ARMS2 rs10490924 minor allele (GT or TT) demonstrated a higher subretinal fluid persistence or recurrence rate and poorer visual outcome following RFPDT. In addition to the ICGA findings, genotyping of ARMS2 (rs10490924) may assist in the selection of patients with cCSC most likely to benefit from RFPDT.

Preoperative clinical factors and visual outcomes following orbital decompression with dysthyroid optic neuropathy.

BACKGROUND: To investigate preoperative clinical factors and visual outcomes of Japanese patients with dysthyroid optic neuropathy (DON) after urgent orbital decompression. METHODS: This retrospective, observational case series study investigated 44 patients who exhibited several preoperative clinical factors that might be associated with the need for urgent orbital decompression due to DON. Additionally, the visual acuity of DON patients was compared between the patients preoperatively and at 1 and 6 months postoperatively. RESULTS: All 44 patients received steroid and with or without radiation therapy, with 27 patients able to avoid undergoing urgent surgery. However, the remaining 17 patients required urgent orbital decompression following a lack of response to the therapy. None of the patients who initially avoided surgery required additional surgery for DON. Factors significantly associated with the need for urgent orbital decompression surgery included: female gender, older age, long disease duration, unilateral significant DON, history of resistance to pulsed steroid therapy, unstable thyroid function, high TRAb (Thyrotrophin receptor antibody)value, poor visual acuity, presence of central diplopia, and presence of corneal problems (P < 0.05 each). The results also showed that postoperative visual outcomes of surgery for DON were acceptable. CONCLUSION: This study revealed several preoperative clinical factors for DON that appear to be associated with the need for urgent orbital decompression surgery in Japanese patients.

Predictive factors of outcome of selective retina therapy for diabetic macular edema.

PURPOSE: To investigate the predictive factors of clinical outcome of selective retina therapy (SRT) for diabetic macular edema (DME). METHODS: This retrospective study included 22 eyes of 22 patients (15 males and 7 females), who were treated with SRT for DME at the Department of Ophthalmology of Osaka City University Hospital and observed at least 6 months after the treatment. The mean age was 64 years (range 40-81). Thirteen of the 22 eyes (59%) had a treatment history other than SRT before. SRT laser (527 nm, 1.7 µs, 100 Hz) was used for treatment. Changes in the best-corrected visual acuity (BCVA) (logMAR) and central macular thickness (CMT) in optical coherence tomography were examined at baseline, 3-month follow-up, and 6-month follow-up. Factors associated with the rate of change in CMT at 3 and 6 months after SRT were examined. RESULTS: The mean BCVA (logMAR) was 0.26 ± 0.31, 0.22 ± 0.27 and 0.23 ± 0.29 at baseline, 3 months and 6 months, respectively (p = 0.15 at 3 months, 0.40 at 6 months; compared to baseline). The mean CMT was 502 ± 163, 493 ± 204, and 416 ± 185 µm at baseline, 3 months, and 6 months, respectively (p = 0.69 at 3 months, 0.01 at 6 months; compared to baseline). The multivariate analysis found a significant negative association with previous macular photocoagulation (p = 0.03) at 3 months and a positive association with a history of insulin use (p = 0.02) and previous panretinal photocoagulation (p = 0.03) at 6 months after SRT. CONCLUSION: The CMT was significantly decreased at 6 months after SRT in DME. The history of insulin use and panretinal photocoagulation may positively and the history of macular photocoagulation may negatively affect the outcome of SRT, which must be considered when determining the therapeutic indications for SRT.

Correlation between visual acuity and human leukocyte antigen DRB1*04 in patients with Vogt-Koyanagi-Harada disease.

BACKGROUND: The common presence of human leukocyte antigen (HLA)-DRB1*04 in Vogt-Koyanagi-Harada (VKH) disease is well known. The aim of this study was to investigate the relationship between visual prognosis and HLA-DRB1*04 alleles during systemic corticosteroid therapy in patients with VKH disease. METHODS: This retrospective case series included 57 eyes from 29 consecutive patients with treatment-naïve VKH disease who received systemic corticosteroid therapy. Visual acuity, sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and final visits. Mean values of parameters were compared with each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primer. RESULTS: Linear regression showed significant differences in logMAR best-corrected visual acuity between the three groups of homozygotes, heterozygotes, and normal subjects at baseline (p < 0.01), at 3 months after treatment (p < 0.01). There was no significant differences at 6 months after treatment (p = 0.257). No significant differences were detected between the three groups in age, sex, refractive error, CRT, CCT, or duration from onset to treatment. CONCLUSION: Alleles of HLA-DRB1*04 might affect visual prognosis and be related to early response after initiation of treatment in VKH disease.

Low-frequency coding variants in CETP and CFB are associated with susceptibility of exudative age-related macular degeneration in the Japanese population.

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. Previous sequencing studies of AMD susceptibility genes have revealed the association of rare coding variants in CFH, CFI, C3 and C9 in European population; however, the impact of rare or low-frequency coding variants on AMD susceptibility in other populations is largely unknown. To identify the role of low-frequency coding variants on exudative AMD susceptibility in a Japanese population, we analysed the association of coding variants of 34 AMD candidate genes in the two-stage design by a multiplex PCR-based target sequencing method. We used a total of 2,886 (1st: 827, 2nd: 2,059) exudative AMD cases including typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation and 9,337 (1st: 3,247 2nd: 6,090) controls. Gene-based analysis found a significant association of low-frequency variants (minor allele frequency (MAF) < 0.05) in CETP, C2 and CFB. The association of CETP remained after conditioned with all known genome-wide association study (GWAS) associated variants. In addition, when we included only disruptive variants, enrichment of rare variants (MAF < 0.01) was also observed after conditioned with all GWAS associated variants (P = 1.03 × 10−6, odds ratio (OR) = 2.48). Haplotype and conditional analysis of the C2-CFB-SKIV2L locus showed a low-frequency variant (R74H) in CFB would be individually associated with AMD susceptibility independent of the GWAS associated SNP. These findings highlight the importance of target sequencing to reveal the impact of rare or low-frequency coding variants on disease susceptibility in different ethnic populations.

Foveal Depression and Related Factors in Patients with a History of Retinopathy of Prematurity.

PURPOSE: This study evaluates optical coherence tomography (OCT) findings of the macula in patients with a history of retinopathy of prematurity (ROP). METHODS: We enrolled 112 patients (age: 6-15 years) and categorized them into 3 groups: gestational age (GA) < 36 weeks with or without a history of ROP (ROP group, preterm group) and GA ≥37 weeks. We included 1 eye of each patient and measured the retinal thickness of the macula by OCT. RESULTS: The ROP group demonstrated the worst VA and the shallowest foveal depression. Furthermore, foveal depression significantly correlated with birth weight, GA, ganglion cell layer/inner plexiform layer (GCL-IPL) thickness, and a history of ROP. CONCLUSIONS: This study established a correlation of fovea formation with premature birth, damage of GCL-IPL, and a history of ROP. The retention of the inner retina possibly contributes to abnormal foveal morphology in patients with a history of ROP.

Retreatment of Exudative Age-Related Macular Degeneration after Loading 3-Monthly Intravitreal Ranibizumab.

PURPOSE: The aim of this study was to investigate the clinical implications of required retreatment after 3-monthly intravitreal ranibizumab (IVR) injections followed by as-needed reinjections up to 5 years in eyes with exudative age-related macular degeneration (AMD). METHODS: A retrospective cohort study was conducted for 165 treatment-naïve eyes from 165 patients with exudative AMD. Visual changes were investigated in terms of the required retreatments. RESULTS: Retreatment-free proportions were 37.0, 23.7, 16.6, 12.1, and 10.5% at 12, 24, 36, 48, and 60 months, respectively. Visual changes were significantly better in eyes which did not require retreatment at every yearly checkpoint within the 5 years. A multivariate logistic regression analysis revealed that requirement of additional IVR treatments in the first 12-24 months was associated with the T allele (risk allele) of ARMS2 A69S (p = 0.010 and 0.015, respectively). Cox regression analysis revealed that older age (p = 0.046) and the T allele of ARMS2 A69S (p = 0.036) were associated with required retreatment within the 5-year follow-up period. CONCLUSIONS: Age and the T allele of ARMS2 A69S are the risk factors requiring retreatments, leading to poor visual change in eyes with exudative AMD following the initial 3-monthly IVR.