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.

Clinical features and associated factors of intraocular inflammation following intravitreal brolucizumab as switching therapy for neovascular age-related macular degeneration.

PURPOSE: The aim of this study is to explore the clinical features and associated factors of intraocular inflammation (IOI) following intravitreal brolucizumab (IVBr) administration for neovascular age-related macular degeneration (nAMD). METHODS: This retrospective study included 87 eyes from 87 Japanese patients with nAMD who were followed up for 5 months after the initial administration of IVBr as switching therapy. Clinical pictures of IOI post-IVBr and changes in best corrected visual acuity (BCVA) at 5 months were evaluated between eyes with and without IOI (non-IOI). The association between IOI and baseline factors (age, sex, BCVA, hypertension, and/or arteriosclerotic changes in the fundus, subretinal hyperreflective material [SHRM], and macular atrophy) was evaluated. RESULTS: Of the 87 eyes, 18 (20.6%) developed IOI and 2 (2.3%) developed retinal artery occlusion. There were 9 (50%) cases of posterior or pan-uveitis among eyes with IOI. The mean interval from initial IVBr administration to IOI was 2 months. The mean changes in logMAR BCVA at 5 months were significantly worse in IOI eyes than in non-IOI eyes (0.09 ± 0.22 vs. - 0.01 ± 0.15, P = 0.03). There were 8 (44.4%) and 7 (10.1%) cases of macular atrophy and 11 (61.1%) and 13 (18.8%) cases of SHRM in the IOI and non-IOI groups, respectively. SHRM and macular atrophy were significantly associated with IOI (P = 0.0008 and P = 0.002, respectively). CONCLUSION: In IVBr therapy for nAMD, eyes with SHRM and/or macular atrophy should be observed more meticulously, given the increased risk of developing IOI, which is associated with insufficient BCVA gain.

Intraoperative Three-Dimensional Fluorescein Angiography-Guided Pars Plana Vitrectomy for the Treatment of Proliferative Diabetic Retinopathy: The Maximized Utility of the Digital Assisted Vitrectomy.

PURPOSE: To show the usefulness of the intraoperative three-dimensional fluorescein angiography (3D-FA)-guided pars plana vitrectomy. METHODS: The NGENUITY 3D visualization system was used for the digital assisted vitrectomy. Three-dimensional fluorescein angiography-guided pars plana vitrectomy was performed in three patients with vitreous hemorrhage secondary to proliferative diabetic retinopathy. We investigated both whether several angiographic findings can be successfully displayed on the screen during 3D-FA and whether pars plana vitrectomy can be performed simultaneously on the same screen while implementing 3D-FA. RESULTS: In all cases, the abnormal FA findings including hypofluorescence due to non-perfusion areas, and the hyperfluorescence due to macular edema and fibrovascular proliferative membrane were successfully displayed on the screen. The segmentation and delamination of fibrovascular proliferative membrane and panretinal photocoagulation for detected non-perfusion areas were able to be performed on the same screen while implementing 3D-FA. CONCLUSION: Three-dimensional fluorescein angiography-guided pars plana vitrectomy is a novel approach that fully utilizes the advantages of digital assisted vitrectomy and a promising option for the treatment of proliferative diabetic retinopathy.

Short-Term Outcomes of Intravitreal Faricimab Injection for Diabetic Macular Edema.

Background and Objectives: Faricimab is a novel bispecific antibody with Fab regions inhibiting both vascular endothelial growth factor-A and angiopoietin-2. Therefore, this study aimed to obtain short-term outcomes of intravitreal injection of faricimab (IVF) for the treatment of diabetic macular edema (DME) in daily clinical practice. Materials and Methods: A retrospective review was carried out on consecutive patients with DME who had been treated with IVF and were followed up for at least 1 month. Outcome measures included changes in logMAR best-corrected visual acuity (logMAR BCVA), central retinal thickness (CRT), number of IVF administrations, and safety. Clinical outcomes were also compared between the treatment-naïve and switch groups. Results: A total of 21 consecutive DME eyes from 19 patients were identified. The mean number of IVFs was 1.6 ± 0.8 during the mean follow-up time of 5.5 months. The overall mean logMAR BCVA following IVF was 0.236, 0.204, 0.190, and 0.224 at baseline, 1, 3, and 6 months, respectively, without a significant change from baseline to 1 month (p = 0.176) or for 6 months (p = 0.923). The overall mean CRT (µm) following IVF was 400.6, 346.6, 342.1, and 327.5 at baseline, 1, 3, and 6 months, respectively. CRT significantly decreased from baseline to 1 month (p = 0.001) but did not reach a significant level over 6 months following IVF (p = 0.070). No significant difference in BCVA or CRT was observed between the treatment-naïve and switch groups. No serious safety concerns were noted. Conclusions: IVF for the treatment of DME may preserve visual acuity and improve macular thickness without serious safety concerns in the short term in a real-world clinical setting.

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.

INTRAOPERATIVE OPTICAL COHERENCE TOMOGRAPHY FOR REAL-TIME VISUALIZATION OF THE POSITIONAL RELATIONSHIP BETWEEN BUCKLING MATERIAL AND RETINAL BREAKS DURING SCLERAL BUCKLING FOR RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To report the usefulness of a new surgical method using intraoperative optical coherence tomography that can more accurately place the buckling material for scleral buckling using a noncontact wide-angle viewing system with a cannula-based chandelier endoilluminator for the treatment of rhegmatogenous retinal detachment. METHODS: The medical records of 12 eyes of 11 patients with rhegmatogenous retinal detachment treated with scleral buckling combined with real-time intraoperative optical coherence tomography observation were retrospectively reviewed. RESULTS: Real-time observations of the positional relationship between the protrusion of buckling material and retinal breaks with intraoperative optical coherence tomography revealed that retinal breaks were not properly placed on the protrusion of the buckling material in five eyes, requiring the intraoperative repositioning of the buckling material. Eventually, the scleral buckling combined with real-time intraoperative optical coherence tomography observation yielded the initial anatomical success rates of 100% without noteworthy intraoperative or postoperative complications. CONCLUSION: This procedure is a novel approach that enables safer and more accurate placement of the buckling material and may contribute to improving the outcomes of scleral buckling in the future.

LONG-TERM EFFECT OF CYSTOTOMY WITH OR WITHOUT THE FIBRINOGEN CLOT REMOVAL FOR REFRACTORY CYSTOID MACULAR EDEMA SECONDARY TO DIABETIC RETINOPATHY.

PURPOSE: To show the long-term effect of cystotomy with or without fibrinogen clot removal for refractory cystoid macular edema secondary to diabetic retinopathy. METHODS: Retrospective analyses of the medical records of 30 eyes of 30 patients with refractory cystoid macular edema secondary to diabetic retinopathy who had followed up for 12 months after the surgery were performed. RESULTS: There were 15 men and 15 women. The mean ± SD age was 68.4 ± 7.9 years. The best-corrected visual acuity (logarithm of the minimal angle of resolution) at 12 months after the surgery (0.33 ± 0.25, Snellen equivalent, 20/42) was statistically better than the preoperative best-corrected visual acuity (0.45 ± 0.33, Snellen equivalent, 20/56) (P < 0.01). The central sensitivity on microperimetry (dB) was not statistically changed between preoperatively (24.0 ± 4.9) and 12 months after the surgery (24.1 ± 4.0) (P = 0.75). The central retinal thickness on optical coherence tomography (µm) at 12 months after the surgery (300.3 ± 99.0) was statistically improved compared with the preoperative central retinal thickness (565.6 ± 198.7) (P < 0.01). During the follow-up period, cystoid macular edema relapsed in seven of 30 eyes. The preoperative cystoid cavity reflectivity on optical coherence tomography in patients with fibrinogen clot removal (n = 16) was significantly higher than that in patients without fibrinogen clot removal (n = 14) (P < 0.04). CONCLUSION: The cystotomy with or without fibrinogen clot removal may be a promising treatment option for refractory cystoid macular edema secondary to diabetic retinopathy.

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.

Drusenoid Pigment Epithelial Detachment: Genetic and Clinical Characteristics.

Few studies report drusenoid pigment epithelial detachment (DPED) in Asians. In this multicenter study, we report the clinical and genetic characteristics of 76 patients with DPED, and, for comparison, 861 patients with exudative age-related macular degeneration (AMD) were included. On the initial presentation, the mean best-corrected visual acuity was 0.087 ± 0.17 (logMAR unit), and mean DPED height and width were 210 ± 132 and 1633 ± 1114 µm, respectively. Fifty-one (67%) patients showed macular neovascularization in the contralateral eye. The risk allele frequency of both ARMS2 A69S and CFH I62V was significantly higher in DPED than in typical AMD and polypoidal choroidal vasculopathy (PCV) (ARMS2 A69S risk allele frequency: DPED 77% vs. typical AMD 66% vs. PCV 57%, CFH I62V risk allele frequency: DPED 87% vs. typical AMD 73% vs. PCV 73%), although the risk allele frequency of both genes was similar between the DPED group and retinal angiomatous proliferation (RAP) group (ARMS2 A69S: p = 0.32, CFH I62V, p = 0.11). The prevalence of reticular pseudodrusen (RPD) was highest in RAP (60%), followed by DPED (22%), typical AMD (20%), and PCV (2%). Although the prevalence of RPD differs between DPED and RAP, these entities share a similar genetic background in terms of ARMS2 and CFH genes.

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.

EFFECTIVENESS OF EN BLOC REMOVAL OF FIBRINOGEN-RICH COMPONENT OF CYSTOID LESION FOR THE TREATMENT OF CYSTOID MACULAR EDEMA.

PURPOSE: To introduce the methodology and outcomes of en bloc removal of the component of cystoid lesion during pars plana vitrectomy as a novel approach for the treatment of cystoid macular edema and show evidence that the component is an aggregation of fibrinogen by mass spectrometry analysis. METHODS: The surgical en bloc extraction of the component of cystoid lesion was performed for cystoid macular edemas secondary to diabetic retinopathy and retinal vein occlusion. Perioperative change of best-corrected decimal visual acuity, and the central retinal thickness and the continuity of subfoveal ellipsoid zone and external limiting membrane on optical coherence tomography were evaluated. Mass spectrometry was performed for the identification of protein constituting the component. RESULTS: Six eyes from six patients were included in the study. In all cases, central retinal thickness was improved after the surgery and remained stable during the follow-up period. Best-corrected decimal visual acuity and the continuity of ellipsoid zone and external limiting membrane were kept in all cases during the follow-up period. The mass spectrometry analysis disclosed that the component was composed of fibrinogen. CONCLUSION: The en block removal of the component of cystoid lesion combined with pars plana vitrectomy may be a promising option for treatment of cystoid macular edema. The component of cystoid lesion is presumably a fibrinogen aggregate.

Medications and fall risk: a case-control study in nursing home residents in Japan.

AIM: Falls are a significant problem for older people, but are few studies of the risk of falling in residents of nursing homes in Japan. We aimed to investigate the risk factors for falls and the association of medication use and falls in nursing home residents in Japan. METHODS: This case-control study reviewed the records of residents of who were ≥ 65 years of age and had fallen in 2012 and an age-, sex-, and facility-matched control group selected from 58 nursing homes in Japan. The odds ratios of potential risk factors and current medications were determined by conditional logistic regression. RESULTS: A total of 1832 residents (916 cases and 916 controls) were included. Falls were significantly associated with an inability to walk without assistance or stand up without assistance, need for toileting assistance, visual impairment, insomnia, and dementia. Current prescription of antithrombotic, nonsteroidal anti-inflammatory, or antiparkinson drugs, muscle relaxants, antiepileptics, antipsychotics, antidepressants, opioids, selective serotonin reuptake inhibitors, and memantine was also associated with increased risk of falling. CONCLUSIONS: Many medications were associated with falls in nursing homes residents in Japan. To prevent these falls, caregivers should provide adequate care, and healthcare professionals should consider switching or dose reduction for these medications.

Impact of Early Vitrectomy for Dense Vitreous Hemorrhage of Unknown Etiology.

BACKGROUND: Surgical intervention for dense vitreous hemorrhage (DVH) with unclear etiology is often delayed in favor of conservative follow-up despite possible disease progression and the availability of safe minimally invasive vitrectomy. OBJECTIVES: The aim of this study is to investigate the efficacy of early surgical intervention for DVH with unknown etiology. METHODS: Eighty-eight cases (88 eyes) of DVH with unknown origin were retrospectively reviewed. Inclusion criteria were as follows: (1) measured visual acuity (VA) of 20/200 or worse and (2) fundus invisibility requiring B-scan ultrasonography. Eyes with a history of diabetic retinopathy, recent trauma, or likely retinal detachment (RD) as revealed by B-scan ultrasonography were excluded. Outcome measures were a cause of vitreous hemorrhage and final VA following early (≤2 weeks after symptom onset) or delayed vitrectomy. RESULTS: The most frequently occurring causes of DVH were central or branch retinal vein occlusion (30 eyes, 34%) and retinal tear or RD (29 eyes, 33%). logMAR VA significantly improved after treatment (p < 0.001). Final VA was significantly higher for eyes treated within 2 weeks compared with eyes treated later than 2 weeks after symptom onset (p = 0.020). CONCLUSIONS: Surgical intervention within 2 weeks after symptom onset may prevent a lower visual outcome.

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.

ARMS2 variants may predict the 3-year outcome of photodynamic therapy for wet age-related macular degeneration.

PURPOSE: To determine the association of age-related maculopathy susceptibility2 (ARMS2) gene polymorphisms with the 3-year outcomes of photodynamic therapy (PDT) in wet age-related macular degeneration (wet AMD). METHODS: The single nucleotide polymorphism (SNP) at rs10490924 in the ARMS2 gene of 65 patients with wet AMD who underwent PDT was genotyped using the TaqMan assay. The clinical characteristics and the outcomes of PDT were compared among the three genotypes at rs10490924. A multivariate regression analysis was performed to evaluate the influence of the clinical cofactors on the association of rs10490924 with the visual outcome at 36 months after the first PDT. RESULTS: A significant difference was found among the genotypes in the age and the baseline lesion size. The patients with the GG genotype showed a significant improvement in vision, and the patients with the TT genotype showed a significant worsening of vision at all time points measured after the initial PDT. In the multivariate regression analysis, the number of the G allele at rs10490924 was associated with a significantly greater improvement in the baseline best-corrected visual acuity (BCVA) at 36 months after the first PDT. CONCLUSIONS: ARMS2 variants are likely associated with the 3-year outcomes of PDT in patients with wet AMD.

One-year outcome of combination therapy with intravitreal aflibercept and verteporfin photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: The purpose of the study was to evaluate the 1-year visual and anatomical outcomes of combination therapy with intravitreal aflibercept (IVA) and verteporfin photodynamic therapy (vPDT) for polypoidal choroidal vasculopathy (PCV), and to determine the predictors of a good visual outcome. METHODS: This was a prospective case-series study. Twenty eyes from 20 treatment-naïve PCV patients were treated with combination therapy with IVA and vPDT. Best-corrected visual acuity (BCVA) and morphological parameters including polypoidal lesions in indocyanine green angiography (ICGA) were evaluated over 12 months of follow-up. RESULTS: The mean logMAR BCVA was significantly improved from 0.30 at baseline to 0.20 at 3 months and 0.18 at 12 months. The mean central retinal thickness was also significantly improved at 3 months and at 12 months. In ICGA, complete regression of polypoidal lesions was found in 14 out of 20 eyes (70 %) at 3 months and in 14 out of 18 eyes (78 %) at 12 months although no ICGA were done on two eyes. In the multivariate logistic regression analyses, the baseline greatest linear dimension was found as a significant predictive factor for good visual improvement (≧0.3 LogMAR units improvement from baseline) at 12 months. CONCLUSION: In this study, combination therapy with IVA and vPDT gave visual and anatomical improvements to treatment-naïve PCV patients over 12 months of follow-up period.