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.

Six-month outcomes of switching from aflibercept to faricimab in refractory cases of neovascular age-related macular degeneration.

PURPOSE: To assess 6-month outcomes of switching from aflibercept to faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) previously requiring monthly injections. METHODS: This multicenter retrospective study examined nAMD eyes receiving monthly aflibercept injections switched to faricimab administered monthly up to 4 injections followed by injections at a minimum of 2-month intervals as per drug labeling. Data regarding age, sex, number of previous injections, treatment intervals, and best-corrected visual acuity (BCVA) were collected. Central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and maximal pigment epithelial detachment (PED) height were measured by optical coherence tomography. RESULTS: The study included 130 eyes of 124 patients. At 6 months, 53 eyes (40.8%) continued on faricimab treatment (Group 1), while 77 eyes (59.2%) discontinued faricimab for various reasons (Group 2) the most common being worse exudation. There were no significant differences between the two groups at baseline. In Group 1, CRT and SFCT significantly decreased at 1 month (P = 0.013 and 0.008), although statistical significance was lost at 6 months (P = 0.689 and 0.052). BCVA and maximal PED height showed no significant changes; however, mean treatment intervals were extended from 4.4 ± 0.5 weeks at baseline to 8.7 ± 1.7 weeks at 6 months (P < 0.001) in Group 1. No clear predictors of response were identified. CONCLUSION: Switching from aflibercept to faricimab allowed for extension of treatment intervals from monthly to bimonthly in roughly 40% of eyes, suggesting that faricimab may be considered in refractory nAMD cases.

A COMPARATIVE STUDY OF MEDIUM-SIZED MACULAR HOLE SURGERY WITH INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE VERSUS CONVENTIONAL PEELING.

PURPOSE: To investigate surgical results for medium-sized (251-400 µ m) macular holes (MHs). METHODS: This retrospective observational study involved 266 eyes of 262 consecutive patients who underwent internal limiting membrane (ILM) peeling (147 eyes in the ILM peeling group) or inverted ILM flap cover technique (119 eyes in the inverted flap group) for primary medium-sized full-thickness MHs. Macular hole associated with retinal detachment, recurrent MH, and traumatic MH were excluded. RESULTS: The primary closure rate for overall medium-sized MHs was 100% (119 of 119 eyes) in the inverted flap group, which was significantly higher than that (94.6% [139/147 eyes]; P = 0.010) in the ILM peeling group. Notably, even after adjusting for the minimum MH diameter, presence of high myopia, or preexisting posterior vitreous detachment, the primary closure rate was significantly better in the inverted flap group than in the ILM peeling group (Cochran-Mantel-Haenszel test, overall adjusted P = 0.006, 0.009, 0.005, respectively). The preoperative and postoperative restoration of the outer retinal layers and visual acuity were comparable between the inverted ILM flap and ILM peeling techniques. CONCLUSION: Primary closure for medium-sized MHs was significantly superior in the inverted flap group than in the ILM peeling group.

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.

The second Japanese family with Malattia Leventinese/Doyne honeycomb retinal dystrophy.

PURPOSE: To describe the clinical and genetic findings of patients in the second Japanese family with Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). METHODS: Two patients (a 41-year-old male proband and his third son) underwent comprehensive ophthalmic examinations, including full-field and multifocal electroretinography (ERG). Sanger sequencing was performed to detect an EFEMP1 gene variant (p.Arg345Trp), which was identified as the only causative pathogenic variant. RESULTS: Genetic analysis revealed that both patients carried the heterozygous variant, but the other unaffected family members did not. Although the proband exhibited innumerable radially distributed drusen in both the posterior poles and good visual acuity at initial presentation, bilateral choroidal neovascularization (CNV) developed during the 15-year follow-up. The proband received 15 intravitreal anti-vascular endothelial growth factor (VEGF) injections in the left eye (LE) and two injections in the right eye (RE). At 56 years of age, his decimal best-corrected visual acuity was 0.1 and 1.2 in the LE and RE, respectively. Full-field ERG showed that while the rod and combined responses were within normal amplitudes, the cone and 30-Hz flicker responses had slightly decreased amplitudes. Multifocal ERG revealed attenuated central responses in the LE and decreased temporal responses in the RE. In the 20-year-old son, multifocal ERG showed normal responses in both eyes. CONCLUSION: This is the first report of ML/DHRD in a patient who developed bilateral CNV and received anti-VEGF treatment in both eyes. Although multifocal ERG exhibited worsening of macular function, the generalized photoreceptor function was preserved until middle age.

Subfoveal choroidal thickness after brolucizumab therapy for neovascular age-related macular degeneration: a short-term multicenter study.

BACKGROUND/PURPOSE: Observation of choroidal thickness after anti-vascular endothelial growth factor (VEGF) therapy may be important for the ideal management of neovascular age-related macular degeneration (AMD). This study investigated changes in subfoveal choroidal thickness (SCT) during loading doses of intravitreal injections of brolucizumab in eyes with neovascular AMD. METHODS: This study included 73 eyes of 72 patients with neovascular AMD at five university hospitals in Japan. All 73 eyes underwent three monthly 6.0 mg intravitreal injections of brolucizumab at baseline, 1 month, and 2 months. The SCT at 3 months was evaluated using optical coherence tomography. RESULTS: The 73 eyes were classified into the treatment-naïve group (43 eyes) and the switched group (30 eyes) that were switched from other anti-VEGF treatments. After three intravitreal injections of brolucizumab, SCT significantly decreased from 236.5 ± 98.8 µm at baseline to 200.4 ± 98.3 µm at 3 months (percent of baseline 84.7%, P < 0.001) in the treatment-naïve group. In the switched group, SCT also significantly decreased from 229.0 ± 113.2 µm at baseline to 216.9 ± 110.2 µm at 3 months (percent of baseline 94.7%, P = 0.039), although the decrease was not as marked compared to that of the treatment-naïve group. CONCLUSION: Intravitreal injections of brolucizumab for neovascular AMD significantly reduced the SCT in both the treatment-naïve and switched groups. Brolucizumab may cause significant anatomic changes in the choroid, particularly in treatment-naïve AMD eyes, possibly more than that previously reported for other anti-VEGF agents.

Bilateral Pachychoroid disease with type 3 Uveal effusion syndrome in one eye and central serous Chorioretinopathy in contralateral eye: a case report.

BACKGROUND: We report a case of bilateral pachychoroid disease with type 3 uveal effusion syndrome (UES) in one eye and central serous chorioretinopathy (CSC) in the contralateral eye. CASE PRESENTATION: A 65-year-old man presented to our department because of decreased vision. Visual acuity was 16/20 in the right eye and 2/20 in the left eye, with normal axial lengths. The left eye was diagnosed with CSC and underwent photocoagulation 8 years ago. The right eye showed inferior non-rhegmatogenous retinal detachment and peripheral choroidal detachment. Macular optical coherence tomography showed submacular fluid in the right eye, pachychoroid in both eyes, and choroidal thickness of 565 µm in the right and 545 µm in the left eye. In both eyes, fluorescence angiography showed window defects and mild fluorescence leakage, and indocyanine green angiography showed dilated choroidal vessels, mild choroidal hyperpermeability, and mild dye leakage. The left eye was diagnosed with chronic CSC. Initially, chronic CSC was also suspected in the right eye. However, photodynamic therapy failed, with worsened retinal detachment and visual acuity. Pachychoroid in the peripheral fundus (choroidal thickness 820 µm) was observed only in the right eye. Based on these findings, UES was diagnosed in the right eye. Sclerectomies were performed. The absence of scleral thickening and glycosaminoglycan deposition led to a final diagnosis of type 3 UES. The procedure was not effective, due to connective tissue regeneration at the sclerectomy sites. In the revision surgery, mitomycin-C was used with sclerectomies. One month after surgery, retinal and choroidal detachment disappeared, visual acuity recovered to 8/20, pachychoroid in the macula and peripheral fundus decreased, and choroidal thickness decreased to 352 µm in the macula and 554 µm in inferior peripheral fundus. CONCLUSIONS: Pachychoroid in the posterior pole was the common finding in type 3 UES and CSC, although extensive pachychoroid in the peripheral fundus may have caused retinal and choroidal detachment in the eye with type 3 UES. Full-thickness sclerectomies with mitomycin-C improved pachychoroid in the peripheral fundus and resolved retinal and choroidal detachment, clearly indicating that the sclera was the main cause of type 3 UES.

A case of bilateral pachychoroid disease: polypoidal choroidal vasculopathy in one eye and peripheral exudative hemorrhagic chorioretinopathy in contralateral eye.

BACKGROUND: We report a case of bilateral pachychoroid disease manifesting polypoidal choroidal vasculopathy (PCV) with punctate hyperfluorescent spot (PHS) in one eye, and peripheral exudative hemorrhagic choroidal retinopathy (PEHCR) with central serous chorioretinopathy (CSC) and PHS in the contralateral eye. CASE PRESENTATION: A 51-year-old healthy woman presented with complaint of blurred vision in her right eye. Corrected visual acuity was 20/20 in the right and 24/20 in the left eye. Fundus examination was normal in the left eye. In the right eye, fundus finding of an orange-red nodular lesion and optical coherence tomography (OCT) finding of polypoidal lesions led to a diagnosis of PCV. Four aflibercept intravitreal injections were performed in her right eye. After treatment, indocyanine green angiography (ICGA) confirmed residual polypoidal lesions with branching vascular networks and PHS with choroidal vascular hyperpermeability. OCT showed PHS associated with small sharp-peaked retinal pigment epithelium (RPE) elevation in peripheral fundus and small RPE elevation in posterior fundus. Based on the above findings, PCV with PHS was finally diagnosed in the right eye. Posttreatment corrected visual acuity in the right eye was 20/20. She presented again 32 months later, with complaint of vision loss in her left eye. Left corrected visual acuity was 20/20, and fundus examination showed mild vitreous hemorrhage. Vitrectomy was performed. In temporal midperipheral fundus, fluorescein angiography revealed CSC, and OCT showed pachychoroid. ICGA depicted abnormal choroidal networks and PHS in peripheral fundus. Furthermore, polypoidal lesions were confirmed by OCT. Based on the above findings, PEHCR and CSC with PHS was finally diagnosed in the left eye. Postoperative corrected visual acuity in the left eye was 20/20, and aflibercept intravitreal injection was performed for prevention of recurrence of vitreous hemorrhage. CONCLUSIONS: This is the first case report of PCV with PHS in one eye, and PEHCR with CSC and PHS in the contralateral eye. This case suggests that PCV, PEHCR, and CSC may be linked pathologies of pachychoroid spectrum disease.

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.

REAL-WORLD EFFECTIVENESS AND SAFETY OF RANIBIZUMAB TREATMENT IN PATIENTS WITH AND WITHOUT POLYPOIDAL CHOROIDAL VASCULOPATHY: Twelve-Month Results From the LUMINOUS Study.

PURPOSE: To evaluate the real-world effectiveness and safety of intravitreal ranibizumab 0.5 mg in treatment-naive patients with and without polypoidal choroidal vasculopathy (PCV). METHODS: Assessment of neovascular age-related macular degeneration patients with or without PCV after 12 months of ranibizumab treatment during the LUMINOUS study. Outcome measures were visual acuity and central retinal thickness changes from baseline and the rate of ocular adverse events. RESULTS: At baseline, 572 and 5,644 patients were diagnosed with and without PCV, respectively. The mean visual acuity gain from baseline at Month 12 in the PCV and non-PCV groups was +5.0 and +3.0 letters, respectively; these gains were achieved with a mean of 4.4 and 5.1 ranibizumab injections. Eighty percent of PCV patients and 72.2% of non-PCV patients who had baseline visual acuity ≥73 letters maintained this level of vision at Month 12; 20.6% and 17.9% of patients with baseline visual acuity <73 letters achieved visual acuity ≥73 letters in these groups. Greater reductions in central retinal thickness from baseline were also observed for the PCV group versus the non-PCV group. The rate of serious ocular adverse events was 0.7% (PCV group) and 0.9% (non-PCV group). CONCLUSION: LUMINOUS confirms the effectiveness and safety of ranibizumab in treatment-naive patients with PCV.

Bilateral multiple serous retinal detachments after treatment with nivolumab: a case report.

BACKGROUND: Immune checkpoint inhibitors have recently been widely used for advanced cancers and are known to cause ocular complications. We herein report a case developing bilateral serous retinal detachments, without ocular inflammation, after starting nivolumab treatment. CASE PRESENTATION: A 73-year-old man was referred to our hospital, having become aware of metamorphopsia 2 months after starting nivolumab (anti-programmed cell death protein 1 monoclonal antibody) for malignant melanoma of the nasal cavity. The initial corrected visual acuity of the right eye was 20/20, and that of the left eye was 20/16. There were no inflammatory findings in the anterior segment or the vitreous. Vitelliform lesions were found in the macular area of both ocular fundi, consistent with serous retinal detachment and subretinal deposits. Swept source optical coherence tomography showed diffuse thickening of the outer photoreceptor segment and thickening of the choroid. Two months after the initial diagnosis, multiple vitelliform lesions were noted, and the fundus findings had worsened. Indocyanine green fluorescein angiography showed delayed inflow in the peripapillary and posterior pole regions in the early phase of imaging. Fundus autofluorescence showed hyperautofluorescence consistent with most of the vitelliform lesions on color fundus photography. CONCLUSIONS: Nivolumab may have impaired the pumping and phagocytosis functions of retinal pigment epithelial cells, resulting in bilateral serous retinal detachments and thickening of the photoreceptor outer segment. This is the first case report, to our knowledge, describing multiple bilateral serous retinal detachments and outer segment thickening without inflammation in a patient treated with nivolumab.

Prospective study of vitrectomy for epiretinal membranes in patients with good best-corrected visual acuity.

BACKGROUND: To evaluate the efficacy of epiretinal membrane removal in patients with good best-corrected visual acuity (BCVA) for improving visual function and quality of life (QOL). METHODS: This prospective case study compared 37 subjects with preoperative BCVA ≦ 0.046 logMAR (Good group) to 35 patients with 0.10-0.52 logMAR (Moderate group) at 3 and 6 months. Linear mixed-effect models were used for statistical analysis. The primary outcome was the horizontal metamorphopsia score (MH) at 6 months postoperatively (post-6 M), while secondary outcomes were postoperative BCVA, vertical metamorphopsia score (MV), aniseikonia, stereopsis and central foveal thickness. In the Good group, QOL was assessed using the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) at 6 and 12 months. RESULTS: MH was significantly improved at post-3 M and post-6 M in the both groups but there were no significant differences between the two groups. MV showed no improvement at the final observation in either group. LogMAR BCVA was significantly improved at post-6 M in the Good group, which had significantly better vision than the Moderate group. Preoperative vertical and horizontal aniseikonia scores remained unchanged in the Good group at post-6 M but worsened in the Moderate group. The NEI VFQ-25 score improved in the Good group, reflecting improved general health, general vision, and mental health. CONCLUSIONS: Early epiretinal surgery for patients with BCVA ≦ 0.046 logMAR was effective for improvement of HM, BCVA, and QOL and prevented worsening of aniseikonia. TRIAL REGISTRATION: UMIN000021220 . Registered 10 September 2015. UMIN Clinical Trials Registry.

Surgical outcomes of 27-gauge and 25-gauge vitrectomy day surgery for proliferative diabetic retinopathy.

PURPOSE: To compare postoperative outcomes of 27-gauge (G) and 25-G vitrectomy conducted as day surgery for proliferative diabetic retinopathy (PDR). METHODS: One hundred eighty-five consecutive PDR patients (185 eyes) who underwent primary vitrectomy (27-G in 64 eyes, 25-G in 121 eyes) were analyzed. RESULTS: The 27-G and 25-G groups did not differ significantly in preoperative Early Treatment Diabetic Retinopathy Study (ETDRS) score, age, or preoperative intraocular pressure. The proportions of simultaneous cataract surgery (27-G vs. 25-G: 59.4% vs. 62.4%) and air-filled eyes (76.6% vs. 85.1%) were not significantly different between two groups. Both groups showed significant improvement in ETDRS score at postoperative 1, 3, and 6 months (all, P < 0.0001). Mean gain in ETDRS score from baseline was apparently better in 27-G group than in 25-G group at 1, 3, and 6 months, but there were no significant differences (1 month: 20.3 vs. 13.1 letters, P = 0.0703; 3 months: 22.9 vs. 17.5 letters, P = 0.1561; 6 months: 24.3 vs. 19.3 letters, P = 0.3313). Operation time was apparently longer for 27-G vitrectomy, but there was no significant difference (54.0 vs. 51.1 min, P = 0.3676). The same was observed for postoperative intraocular pressure at postoperative day 1 (19.7 vs. 18.1 mmHg, P = 0.1353). Incidence of postoperative retinal detachment (1.6% vs. 0.8%) and reoperation due to vitreous hemorrhage (6.3% vs. 6.6%) was not different between two groups. CONCLUSIONS: The 27G system is as safe and as useful as the 25G system when used for PDR and can be expected to achieve earlier recovery of postoperative visual acuity.

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.

Comparative study of 27-gauge and 25-gauge vitrectomy performed as day surgery.

PURPOSE: To compare postoperative outcomes of 27-gauge (G) and 25-G vitrectomy conducted as day surgery. METHODS: In total, 200 consecutive eyes that underwent primary vitrectomy (27-G in 100 eyes, 25-G in 100 eyes) were analyzed. 27-G vitrectomy was performed using a cut rate of 7500 cpm and 25-G vitrectomy using a cut rate of 5000 cpm. RESULTS: The 27-G and 25-G groups did not differ significantly in underlying diseases and preoperative Early Treatment Diabetic Retinopathy Study (ETDRS) score. The time required for vitrectomy was significantly longer in the 27-G group (35.3 vs. 29.8 min, P = 0.0013). Postoperative hypotony was observed in 0 and 3 patients, and ocular hypertension in 10 and 14 patients in the 27-G and 25-G groups, respectively, showing more stabilized postoperative ocular pressure in the 27-G group. Gain in ETDRS score was significantly better in the 27-G group (12.1 ± 20.2 letters) compared to the 25-G group (10.0 ± 21.3 letters) (P = 0.0323) at 1 month post-vitrectomy, but not significantly different at 3 and 6 months (P = 0.0686 and 0.0543). Rates of postoperative retinal detachment (1 vs. 1%) and vitreous hemorrhage (2 vs. 3%) were not different between two groups. CONCLUSIONS: 27-G vitrectomy requires longer operative time than 25-G, but using the 27-G system results in earlier visual improvement and stabilized ocular pressure.

Postoperative roll cake-like macular fold after retinal detachment surgery.

PURPOSE: To report a case developing a severe retinal fold (RF), resembling a roll cake on optical coherence tomography (OCT), after retinal detachment (RD) surgery. CASE REPORT: A 61-year-old man underwent vitrectomy for a limited macula-on-superior rhegmatogenous RD and gas tamponade at another hospital. Despite remaining prone for 4 days, RF was noted after gas disappearance and he was referred to us. OCT showed a roll cake-like RF, which resolved after vitrectomy with internal limiting membrane (ILM) peeling, creation of a new detachment, perfluorocarbon liquid injection, air-fluid exchange, silicone oil tamponade and prone positioning. CONCLUSION: ILM peeling including the area of the retinal fold, followed by new detachment creation and finally perfluorocarbon liquid injection, effectively flattened the severe RF. To our knowledge, this is the most severe case of RF to be documented by OCT and illustrates that broad ILM peeling, including the RF, is effective for treating RF.

27-gauge and 25-gauge vitrectomy day surgery for idiopathic epiretinal membrane.

BACKGROUND: This study compared the postoperative outcomes of 27-gauge (G) and 25-G vitrectomy performed for the treatment of idiopathic epiretinal membrane (ERM). METHODS: The study design was single center, retrospective, interventional case series. Two hundred consecutive eyes that underwent primary vitrectomy for ERM (27-G vitrectomy in 100 eyes and 25-G vitrectomy in 100 eyes) were studied for 6 months. In all eyes, scleral tunnels were made using angle incisions, and air or gas exchange was performed. RESULTS: There were no significant differences in age, spherical diopter power, as well as preoperative Early Treatment Diabetic Retinopathy Study (ETDRS) score, central retinal thickness (CRT), and intraocular pressure between the 27-G and 25-G groups. The proportions of simultaneous cataract surgery (27-G vs. 25-G: 82% vs. 90%), air-filled eyes (99% vs. 98%), and scleral wound suture at the end of surgery (0% vs. 0%) were not significantly different between two groups. The mean operation time for vitrectomy was significantly (P = 0.0322) longer by 4 min for 27-G (37 min) compared to 25-G (33 min) vitrectomy. Gain in ETDRS score was significantly (P = 0.0421) better in 27-G group (4.7 ± 8.1 letters) compared to 25-G group (1.1 ± 13.6 letters) at 1 month post-vitrectomy, but not significantly different at 3 and 6 months (P = 0.0835 and 0.0569, respectively). Decrease in CRT was significantly (P = 0.0354) greater in 27-G group (-24.2 ± 50.0 µm) compared to 25-G group (-8.0 ± 48.6 µm) at 1 month post-vitrectomy, but not significantly different at 3 and 6 months (P = 0.6059 and 0.1725, respectively). On postoperative day 1, hypotony (≤ 6 mmHg) was observed in 2 eyes in 27-G group and 6 eyes in 25-G group, while ocular hypertension (≥ 25 mmHg) was found in 4 eyes in 27-G group and 11 eyes in 25-G group, with no significant differences between two groups. Postoperative complications requiring treatment occurred in one eye (vitreous hemorrhage) in 27-G group, and in two eyes (vitreous hemorrhage and retinal detachment in one eye each) in 25-G group. CONCLUSIONS: Although 27-G vitrectomy requires operation time of 4 min longer compared to 25-G vitrectomy for ERM surgery, using the 27-G system results in earlier recovery of visual acuity, CRT improvement and stabilized ocular pressure.

Comparison of pro re nata versus Bimonthly Injection of Intravitreal Aflibercept for Typical Neovascular Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to clarify the 1-year outcomes of pro re nata (PRN) and bimonthly intravitreal injections of aflibercept (IVA) for typical neovascular age-related macular degeneration (tAMD) after the initial 3 monthly IVA. METHODS: We conducted a prospective, interventional study. Fifty-eight treatment-naïve patients with tAMD were randomly assigned to the PRN (30 patients) or the bimonthly (28 patients) treatment group. Both groups initially received 3 monthly IVA. Visual acuity, central macular retinal thickness (CRT), and central choroidal thickness (CCT) were evaluated at 12 months. Subanalysis was performed to identify factors associated with the best-corrected visual acuity (BCVA). RESULTS: BCVA was significantly improved only in the bimonthly group at 12 months. CRT and CCT were significantly decreased in both groups. Subanalysis showed that the only factor associated with BCVA improvement at 12 months was the existence of pigment epithelial detachment at baseline. CONCLUSIONS: BCVA showed significant improvement only in the bimonthly group but not in the PRN group at 12 months.

A Multicenter Randomized Controlled Study of Antioxidant Supplementation with Lutein for Chronic Central Serous Chorioretinopathy.

PURPOSE: To investigate functional and morphological changes in patients with chronic central serous chorioretinopathy after supplementation with antioxidants containing lutein or a placebo. PROCEDURES: One hundred eyes of 100 patients were randomly divided into 2 groups, one taking tablets with lutein plus other antioxidants and the other taking a placebo for 6 months. Best-corrected visual acuity (BCVA) and the subfoveal fluid height on optical coherence tomography were measured. RESULTS: Seventy-nine patients (37 in the supplementation and 42 in the placebo group) completed the 6-month follow-up. In the supplementation group, mean BCVA showed significant improvement (p = 0.003), while there was no significant change in the placebo group (p = 0.589). The mean subfoveal fluid height was significantly reduced, by 28.6%, in the supplementation group (p = 0.028), in contrast to 3.3% in the placebo group (p = 0.898). CONCLUSIONS: Antioxidant supplementation significantly reduced subfoveal fluid height. The impacts of antioxidant supplementation on BCVA remain to be elucidated in future studies.