A large-scale, observational study to investigate the current status of diabetes complication and their prevention in Japan: incidence/risk factors for malignancies during follow-up-JDCP study 11 (English version).

In the large-scale, prospective, observational JDCP study, a total of 5944 people with type 2 diabetes (mean age at baseline, 61.4 years old; women, 39.9%; and duration of diabetes, 10.8 years) were followed up for incidence of malignancy. During a mean 5.38 ± 2.92 years of follow-up, malignancies occurred in 322 individuals, accounting for a crude incidence of 10.35/1000 person-years. The 3 most frequently reported malignancies included colorectal cancers (20.4%), breast cancer (16.5%) and lung cancers (13.6%) in women, and gastric cancers (18.3%), colorectal cancers (15.7%) and lung/prostate cancers (12.7%) in men. During follow-up, men had a significantly higher relative risk for malignancy than women. In contrast, women had a significantly shorter time to the first diagnosis of malignancy following a diagnosis of diabetes than men (13.79 ± 7.90 and 17.11 ± 8.50 years, respectively), although there was no marked difference in the age at the diagnosis of malignancy (67.39 ± 7.27 and 68.44 ± 6.62 years, respectively). Cox proportional hazard models revealed that increasing age, a history of drinking and a history of acute myocardial infarction were significantly associated with an increased risk of malignancy. This report may be of interest in that it provides valuable insight into which malignancies Japanese people with type 2 diabetes are likely to be at risk of developing over time.

Seven-year outcome after 1-year fixed regimen of intravitreal aflibercept injections followed by pro re nata treatment for neovascular age-related macular degeneration.

PURPOSE: The study aims to investigate the 7-year best-corrected visual acuity (BCVA) course after 1-year fixed regimen of intravitreal aflibercept injection (IVA) for neovascular age-related macular degeneration (nAMD) and to identify factors affecting this BCVA. METHODS: This longitudinal, observational study included 63 treatment-naïve eyes (61 patients) with nAMD, treated with 1-year fixed regimen of IVA-3 monthly injections and 4 subsequent bimonthly injections-essentially followed by PRN regimen of IVA but sometimes followed by agent switching, photodynamic therapy (PDT), or vitrectomy, as needed. We assessed BCVA changes over a 7-year period. Morphologically, we assessed central retinal thickness (CRT), central choroidal thickness (CCT), subfoveal pigment epithelial detachment (PED) height, vitreomacular traction/adhesion (VMT/VMA), epiretinal membrane (ERM), and macular atrophy involving the fovea. RESULTS: Logarithm of the minimum angle of resolution (logMAR) BCVA changed from 0.20 ± 0.24 to 0.29 ± 0.45 over 7 years. BCVA improved significantly after years 1 and 2 (P = 0.002 and 0.001, respectively) and then slowly decreased. BCVA after years 3-7 did not significantly differ from baseline. CRT and CCT decreased significantly during follow-up, while PED height did not. VMT/VMA decreased significantly, whereas ERM and macular atrophy increased significantly. Seven-year and baseline BCVA positively correlated (P = 0.007, ß = 0.35). CONCLUSIONS: BCVA was maintained for 7 years in nAMD eyes after 1-year fixed regimen of IVA, essentially followed by PRN regimen, but sometimes followed by agent switching, PDT, or vitrectomy, without severe drug-induced complications. Thus, early diagnosis and treatment of nAMD are essential for maintaining good long-term BCVA, even in eyes with relatively poor baseline vision.

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.

Macular atrophy at 5 years after photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To investigate predictors for macular atrophy (MA) involving the fovea after photodynamic therapy (PDT) followed by pro re nata (PRN) treatment for polypoidal choroidal vasculopathy (PCV). METHODS: This prospective observational study analysed treatment-naïve eyes with symptomatic PCV without MA at baseline which were followed up for 5 years. All eyes were initially treated with PDT, followed by a PRN regimen of anti-vascular endothelial growth factor (VEGF) therapy and/or PDT. We assigned eyes with and eyes without development of MA involving the fovea 5 years after the initial treatment into MA and non-MA groups, respectively. Baseline parameters and the number of treatments were compared between the two groups. RESULTS: Seventy-two eyes of 69 consecutive patients were included, and 29 eyes of 29 patients were analysed. Twelve (41%) and 17 (59%) eyes were assigned into the MA and non-MA groups, respectively. There were significant differences in subfoveal choroidal thickness (226.2 ± 47.8 µm vs. 278.8 ± 68.1 µm, P = 0.03) and number of anti-VEGF injections (13.7 ± 9.6 vs. 5.4 ± 5.6, P = 0.007) between the MA and non-MA groups, but not in the number of PDT sessions (P = 0.71). Best-corrected visual acuity at 5 years in the MA group was lower than in the non-MA group (P = 0.048). CONCLUSION: Our long-term observation suggests that a thin subfoveal choroid at baseline and many followed anti-VEGF injections in a PRN regimen increase the risk for development of MA involving the fovea 5 years after PDT.

Effectiveness of Reduced-fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy: A Propensity Score Analysis.

Purpose: To investigate the 2-year effectiveness of reduced-fluence photodynamic therapy (rf-PDT) for chronic central serous chorioretinopathy (cCSC). Design: Retrospective cohort study. Participants: A total of 223 consecutive patients with newly diagnosed cCSC with active serous retinal detachment (SRD) were included from May 2007 to June 2017 and followed up for at least 2 years. Patients who underwent ocular treatment other than cataract surgery before the beginning of recruitment and those who had macular neovascularization at baseline were excluded. Methods: All patients underwent a comprehensive ophthalmic evaluation, including measurements of best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain OCT. An inverse probability of treatment weighting (IPTW) methodology was applied to balance 18 baseline characteristics between patients who received rf-PDT (rf-PDT group) and those who did not receive treatment (controls). Inverse probability of treatment weighting survival analysis and regression were performed. Main Outcome Measures: The proportion of patients whose BCVA at 24 months was the same or improved compared with the baseline visual acuity (VA) (VA maintenance rate). Results: A total of 155 eyes (rf-PDT group: 74; controls: 81) were analyzed. The patients' backgrounds were well balanced after IPTW with standardized differences of < 0.10. An IPTW regression analysis revealed that the VA maintenance rate was significantly higher in the rf-PDT group than in the controls (93.6% vs. 70.9%, P < 0.001, 12 months; 85.7% vs. 69.8%, P = 0.019, 24 months). The rf-PDT group tended to show better VA improvement, but was not statistically significant (-0.06 vs. -0.008, P = 0.07, 12 months; -0.06 vs. -0.03, P = 0.32, 24 months). An IPTW Cox regression showed a significantly higher rate of complete SRD remission in the rf-PDT group (hazard ratio, 5.05; 95% confidence interval, 3.24-7.89; P < 0.001). Conclusions: The study suggests the beneficial effect of rf-PDT for cCSC for both VA maintenance and higher proportion of complete SRD remission in the clinical setting.

Association between central serous chorioretinopathy susceptibility genes and choroidal parameters.

PURPOSE: To evaluate the association between central serous chorioretinopathy (CSC) susceptibility genes and choroidal parameters in a large Japanese cohort. STUDY DESIGN: Retrospective cohort study. METHODS: Of the 9850 individuals in the Nagahama study whose second visit was between 2013 and 2016, those with optical coherence tomography (OCT) images with enhanced depth imaging (EDI), axial length, and genome-wide single nucleotide polymorphism (SNP) genotyping data were included. We calculated subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), normalized choroidal intensity (NCI), and vertical asymmetry of choroidal thickness. Genome-wide quantitative trait locus (QTL) analyses were performed for each parameter. We screened for four CSC susceptibility SNPs: CFH rs800292, TNFRSF10A rs13278062, GATA5 rs6061548, and VIPR2 rs3793217. Whenever an SNP was not included in the genotyping data after quality control, its proxy SNP was selected. RESULTS: In total, 4586 participants were evaluated. CFH rs800292 was significantly associated with SFCT (P < 0.001) and CVI (P < 0.001). VIPR2 rs3793217 was significantly associated with SFCT (P < 0.001) but not with CVI. Whereas, TNFRSF10A rs13254617 and GATA5 rs6061548 were not significantly associated with SFCT or CVI. None of these SNPs was associated with NCIEDI and asymmetry of choroidal thickness. CONCLUSION: CFH, VIPR2, TNFRSF10A, and GATA5 showed different association patterns with choroidal parameters. Although the mechanism of CSC pathogenesis by choroidal changes is not fully understood, this finding suggests that each gene may be involved in different mechanisms of CSC development. Our genetic study provides a basis for understanding the role of CSC susceptibility genes.

Relationship between Pachychoroid and Polypoidal Choroidal Vasculopathy.

Previous clinical studies have suggested that pachychoroid can induce macular neovascularization (MNV) to develop pachychoroid neovasculopathy (PNV) and that PNV can progress to polypoidal choroidal vasculopathy (PCV). Recent studies based on the pachychoroid concept are now gradually revealing the true nature of, at least some part of, PCV. However, previous studies on PNV and/or PCV have used different frameworks for the classification of PNV, PCV, and neovascular age-related macular degeneration (nAMD). These have hampered the rapid overhaul of the understanding of PCV. Some investigators have assumed that all PCV is pachychoroid-driven whereas other investigators have classified PCV into "pachychoroid PCV" and "non-pachychoroid PCV". Furthermore, since there is no consensus as to whether PNV includes PCV, some studies have included PCV with PNV, while other studies have excluded PCV from PNV. To address these gaps, we summarize previous studies on PCV and pachychoroid. Even before the proposal of the pachychoroid concept, previous studies had suggested that PCV could be divided into two subtypes, of which one was characterized by pachychoroid features. Previous studies had also provided keys to understand relationship between PCV and PNV. We here recommend a refined conceptual framework for future studies on PNV, PCV, and nAMD. Considering the current inconsistent understanding of PCV, we should be cautious about using the term PCV until we understand the true nature of PCV.

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.

Treatment of diabetic macular edema in real-world clinical practice: The effect of aging.

AIMS/INTRODUCTION: In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. MATERIALS AND METHODS: This is a real-world clinical study including 1,552 patients with treatment-naïve center-involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55-64; C3, 65-74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years. RESULTS: From baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were -0.01 in C1, -0.06 in C2, -0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were -136.2 µm in C1, -108.8 µm in C2, -100.6 µm in C3, and -89.5 µm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti-VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001). CONCLUSIONS: Compared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real-world clinical practice.

CONTRAST-TO-NOISE RATIO IS A USEFUL PREDICTOR OF EARLY DISPLACEMENT OF LARGE SUBMACULAR HEMORRHAGE BY INTRAVITREAL SF6 GAS INJECTION.

PURPOSE: To investigate predictors of early displacement of submacular hemorrhage (SMH) by simple intravitreal SF6 gas injection. METHODS: This retrospective study included 16 eyes of 16 consecutive patients (age: 74.5 ± 7.7 years; 15 men) with large SMH treated with simple intravitreal SF6 gas before inception of subretinal tissue plasminogen activator injection at our institution. The SMH displacement was graded at 1-week posttreatment as 0, 1, or 2. Central retinal thickness, central choroidal thickness, SMH height, SMH area, disease duration, use of anticoagulant or antiplatelet drugs, and contrast-to-noise ratio (CNR) of SMH on optical coherence tomography images were recorded. Correlations between displacement grading and baseline parameter were analyzed. RESULTS: Univariable correlation analysis revealed association of the 1-week displacement grading with the CNR (P = 0.004; r = -0.68) and SMH height (P = 0.03; r = -0.55). The CNR was most strongly associated with 1-week displacement on multivariable correlation analysis (P = 0.01; ß = -0.60). CONCLUSION: Findings of the present study showed that the CNR of SMH was a useful predictor of early displacement of large SMH after simple intravitreal SF6 gas injection. When vitrectomy with subretinal injection of tissue plasminogen activator is difficult in patients with large SMH, with low CNR on optical coherence tomography, simple intravitreal SF6 gas injection may be a treatment option.

PREDICTORS OF RETINAL PIGMENT EPITHELIUM TEAR DEVELOPMENT AFTER TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: The purpose of this study was to investigate the predictors of retinal pigment epithelium (RPE) tear development after treatment for neovascular age-related macular degeneration using swept source optical coherence tomography angiography. METHODS: This prospective study included 152 treatment-naïve eyes with neovascular age-related macular degeneration without high myopia that were followed up for 1 year after treatment. Eligible eyes were classified into eyes with or without RPE tear development. They were matched in a 1:2 ratio. The areas of choroidal neovascularization (CNV) and RPE detachment (pigment epithelial detachment [PED]) were measured from optical coherence tomography angiography and OCT en face images, respectively. The optical coherence tomography angiography-specific parameters representing CNV status were analyzed. RESULTS: Eight (5.3%) of the 152 eyes developed RPE tears (RPE tear group). After matching, 16 eyes without RPE tears were analyzed (non-RPE tear group). The ratio of the CNV/PED area was lower in the RPE tear group than that in the non-RPE tear group (P = 0.007). The PED area was broader (P = 0.008), and PED height was greater in the RPE tear group (P = 0.04). Optical coherence tomography angiography-specific parameters did not differ between the two groups. CONCLUSION: Neovascular age-related macular degeneration with pretreatment broad PED, high PED, and small CNV area relative to the PED area has a high risk of RPE tear development after therapy. However, CNV status may not have an association.

Rescue photodynamic therapy for age-related macular degeneration refractory to anti-vascular endothelial growth factor monotherapy.

BACKGROUND: To evaluate the 3-year outcome in eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal anti-vascular endothelial growth factor monotherapy or rescue therapy using standard verteporfin photodynamic therapy (PDT), and corroborate efficacy of rescue PDT. METHODS: Patients were administered aflibercept injections once a month for 3 months followed by once every 2 months in the first year. After year 1, treatment with aflibercept monotherapy as indicated or in combination with PDT at the retinal specialist's discretion. Only cases completing the three-year follow-up were included. Regression analysis with visual acuity and macular atrophy at year 3 was performed for the dependent variable. RESULTS: Of the 292 eyes, 15 eyes underwent rescue PDT following year 1. The best-corrected visual acuity (logarithm of minimal angle of resolution, mean/Snellen equivalent ± SD) was 0.35 (20/45) ± 0.38, 0.23 (20/30) ± 0.36, 0.26 (20/35) ± 0.38, and 0.31 (20/40) ± 0.42 at baseline, year 1, year 2, and year 3, respectively. Multiple regression analysis revealed that the rescue PDT was significantly associated with macular atrophy and poor visual outcome at year 3 (odds ratio = 1.2, p < 0.001; ß = 0.23, p = 0.0029, respectively). CONCLUSIONS: The visual outcome in eyes with nAMD retained baseline levels at year 3; however, patients treated with rescue PDT developed macular atrophy more frequently and poor visual outcomes.

Macular hole closure at seven years after surgery.

PURPOSE: To report a case of macular hole (MH) closure at seven years after internal limiting membrane (ILM) peeling. OBSERVATIONS: A 66-year-old woman developed a MH in her left eye. Pars plana vitrectomy with ILM peeling and SF6 gas injection followed by face-down position for a week slightly improved the visual acuity from 20/400 to 20/200 but did not close the MH. During subsequent three years of follow-up without any treatment, the MH did not close. Seven years after the surgery, she visited us for cataract surgery in her right eye, and the optical coherence tomography (OCT) examination coincidentally found closure of the MH in her left eye. The visual acuity of her left eye remained 20/200 despite the MH closure. CONCLUSIONS AND IMPORTANCE: ILM peeling might indirectly contribute to the closure of MH at seven years after the surgery although the mechanism is unclear. Sharing the serial OCT images until the MH closure would help us explore the mechanisms of ILM peeling to close MH and develop rational surgery technique manipulating ILM for MH.

Pachychoroid-phenotype effects on 5-year visual outcomes of anti-VEGF monotherapy in polypoidal choroidal vasculopathy.

PURPOSE: To investigate whether the efficacy of anti-vascular endothelial growth factor (VEGF) monotherapy for polypoidal choroidal vasculopathy (PCV) differs between pachychoroid and non-pachychoroid phenotypes in the long term. METHODS: This retrospective longitudinal study included 115 treatment-naïve eyes in 115 consecutive patients with symptomatic PCV who were treated with anti-VEGF monotherapy and were followed up for 5 years. Eligible eyes were assigned to either a pachy-PCV group, with a pachychoroid phenotype, or a non-pachy-PCV group, without a pachychoroid phenotype. Best-corrected visual acuity (BCVA) and other parameters over a 5-year period were compared between the groups. RESULTS: Forty-eight eyes and 67 eyes were classified into the pachy-PCV and non-pachy-PCV groups respectively. Baseline and 5-year BCVA (logarithm of the minimum angle of resolution) were 0.19 ± 0.20 and 0.16 ± 0.28 in the pachy-PCV group, respectively, and 0.25 ± 0.26 and 0.26 ± 0.36 in the non-pachy-PCV group respectively. BCVA did not change significantly in either group (p = 0.18 and 0.08 respectively). BCVA did not differ between the groups at any observation time-point. Subfoveal choroidal thickness (SFCT) at baseline and at 5 years was significantly higher in the pachy-PCV group than in the non-pachy-PCV group (both p < 0.001); however, the mean rate of decrease in SFCT did not differ in either group over the 5-year period (22% vs. 23%, p = 0.81). CONCLUSION: Our findings suggest that anti-VEGF monotherapy was similarly effective for pachychoroid- and non-pachychoroid-phenotype eyes with PCV, for at least 5 years, although further studies are required.

Visual acuity outcomes of anti-VEGF treatment for neovascular age-related macular degeneration in clinical trials.

Anti-VEGF treatment for neovascular age-related macular degeneration (nAMD) has been evaluated in clinical trials. To select the best anti-VEGF drug and the best treatment regimen for nAMD, a thorough understanding of the characteristics of each anti-VEGF drug and treatment regimen is essential. In this review, we summarized visual acuity (VA) changes in 30 previous clinical trials of anti-VEGF treatment for nAMD. In most studies, ranibizumab, aflibercept, and brolucizumab improved the VA by 6 to 12 letters from the baseline VA of 50-65 letters and maintained the VA improvement regardless of the treatment regimen; the VA improved from 0.2-0.4 to 0.3-0.7 in Snellen equivalents. The improvement was rapid during the first month and became slower after the second injection, and 60% to 90% of the VA improvement was attained within the first 3 months. The upper limit of the VA improvement should be determined according to eyes with nAMD themselves, not according to anti-VEGF drugs or treatment regimens. Since a fixed regimen can result in overtreatment, whilst a pro re nata regimen can result in insufficient treatment, a treat-and-extend regimen would be optimal to treat nAMD. Insufficient treatment fails to improve VA to the upper limit and/or to maintain the improved VA, whereas overtreatment can cause macular atrophy. One study reported no difference in the risk of macular atrophy between ranibizumab and aflibercept, whilst many studies have suggested that aflibercept causes more choroidal thinning, one of the risk factors for macular atrophy, than does ranibizumab. Further evaluation of drugs and regimens should be performed from the viewpoint of complications and minimum number of injections required to improve and maintain VA.

IMI Pathologic Myopia.

Pathologic myopia is a major cause of visual impairment worldwide. Pathologic myopia is distinctly different from high myopia. High myopia is a high degree of myopic refractive error, whereas pathologic myopia is defined by a presence of typical complications in the fundus (posterior staphyloma or myopic maculopathy equal to or more serious than diffuse choroidal atrophy). Pathologic myopia often occurs in eyes with high myopia, however its complications especially posterior staphyloma can also occur in eyes without high myopia. Owing to a recent advance in ocular imaging, an objective and accurate diagnosis of pathologic myopia has become possible. Especially, optical coherence tomography has revealed novel lesions like dome-shaped macula and myopic traction maculopathy. Wide-field optical coherence tomography has succeeded in visualizing the entire extent of large staphylomas. The effectiveness of new therapies for complications have been shown, such as anti-VEGF therapies for myopic macular neovascularization and vitreoretinal surgery for myopic traction maculopathy. Myopia, especially childhood myopia, has been increasing rapidly in the world. In parallel with an increase in myopia, the prevalence of high myopia has also been increasing. However, it remains unclear whether or not pathologic myopia will increase in parallel with an increase of myopia itself. In addition, it has remained unclear whether genes responsible for pathologic myopia are the same as those for myopia in general, or whether pathologic myopia is genetically different from other myopia.

Long-Term Visual Outcome in Inferior Posterior Staphyloma and Efficacy of Treatment for Complicated Choroidal Neovascularization.

PURPOSE: To investigate long-term visual outcome in inferior posterior staphyloma (IPS) in each group classified based on macular complications and to examine the treatment effect for eyes with IPS with choroidal neovascularization (CNV). DESIGN: Prospective clinical cohort study. PARTICIPANTS: We analyzed 56 eyes of 43 consecutive patients with IPS who were followed for 4 years. METHODS: We classified eligible eyes into 3 groups based on baseline findings: eyes without CNV or retinal exudate (no-exudate group), eyes without CNV and with retinal exudate (exudate group), and eyes with CNV (CNV group). We investigated the best-corrected visual acuity (BCVA) and associated parameters for 4 years. RESULTS: BCVA declined during 4 years only in the exudate group (P = .002), whereas it was maintained for 4 years in the no-exudate and CNV groups (P = .53 and .20, respectively). Baseline BCVA was lower in the CNV group than in the exudate group (P = .004); however, the 4-year BCVA was not (P = .84). The 4-year BCVA was associated with baseline BCVA in all groups. Eyes in the CNV group required 9.0 ± 8.7 anti-vascular endothelial growth factor therapy in 4 years. CONCLUSIONS: Better baseline BCVA in eyes with exudative IPS without CNV spontaneously declined in 4 years, whereas worse baseline BCVA in eyes with IPS with CNV did not, probably because of treatment for retinal exudate from CNV. Anti-vascular endothelial growth factor therapy would be effective for long-term maintenance of BCVA in eyes with IPS with CNV, similar to other diseases with CNV.

Effects of Intravitreous Aflibercept Injection in Pachychoroid Neovasculopathy: Comparison with Typical Neovascular Age-Related Macular Degeneration.

PURPOSE: To compare the 12-month efficacy of intravitreous aflibercept (IVA) injection between eyes with pachychoroid neovasculopathy and neovascular age-related macular degeneration (AMD). METHODS: Retrospective, comparative case series analysis. Twenty-seven eyes with pachychoroid neovasculopathy and sixty-three eyes with neovascular AMD. All patients received three initial monthly, followed by bimonthly, IVA injections. RESULTS: Twelve months after initial treatment, the mean best-corrected visual acuity (BCVA) had improved both in pachychoroid neovasculopathy (from 0.28 to 0.14 logMAR; P = 0.001) and neovascular AMD (from 0.40 to 0.29 logMAR; P < 0.001). Twelve months after initial treatment, eyes with pachychoroid neovasculopathy exhibited decreased mean central retinal thickness (CRT) and subfoveal choroidal thickness (both, P < 0.001) and presence of polyps (P = 0.039) and improved integrity of external limiting membrane (ELM) (P = 0.008) and ellipsoid zone band (P = 0.001). At the 12-month follow-up, 77% and 68% of eyes with pachychoroid neovasculopathy and neovascular AMD, respectively, exhibited dry macula (P = 0.30). Baseline CRT was correlated with 12-month BCVA in eyes with pachychoroid neovasculopathy (P = 0.02). In eyes with neovascular AMD, CRT (P = 0.005) and presence of intact ELM (P = 0.007) were significant predictors of 12-month BCVA. CONCLUSION: Periodic IVA injection leads to anatomical and functional improvement in eyes with pachychoroid neovasculopathy and in eyes with neovascular AMD.