Effect of Duration of Macular Detachment on Visual Prognosis after Surgery for Macula-Off Retinal Detachment: Japan-Retinal Detachment Registry.

PURPOSE: To evaluate the association between the duration of macular detachment (DMD) and visual prognosis in patients with macula-off rhegmatogenous retinal detachment (RD). DESIGN: Prospective observational cohort study. PARTICIPANTS: This study analyzed 719 eyes with macula-off rhegmatogenous RD registered with the Japan-Retinal Detachment Registry created by the Japan Retina and Vitreous Society. METHODS: We included patients with macular detachment without a history of prior surgery, except cataract surgery and vitrectomy. Reoperation cases, hereditary RD, and macular hole RD were excluded. We compared the visual prognosis between patients with DMD of N days or less and those with DMD of N + 1 days or more (N = 2-5). For these 4 comparisons, the inverse probability of treatment weighting (IPTW) methodology was employed, to balance 20 baseline characteristics between the shorter and longer DMD groups. The baseline characteristics included age, sex, axial length, baseline visual acuity, operative procedures, and detailed characteristics of RD. P-values < 0.01 were considered statistically significant. MAIN OUTCOME MEASURES: The best-corrected visual acuity (BCVA) 6 months after surgery. RESULTS: The final analysis included 719 eyes. For all comparisons, the patients' backgrounds were well balanced after IPTW with standardized differences < 0.10. The IPTW regression analysis revealed that the BCVA after 6 months was significantly better after surgeries for DMD of ≤ 2 days than that for DMD of ≥ 3 days. Similarly, the 6-month BCVA for surgeries for DMD of ≤ 3 days was significantly better than that for surgeries for DMD of ≥ 4 days (differences in logarithm of the minimum angle of resolution: -0.113, P = 9.1 × 10-7; -0.076, P = 1.6 × 10-3, respectively). On the other hand, there were no statistically significant differences for the other comparisons. CONCLUSIONS: Earlier surgical treatment within 3 days from the onset of macular detachment should be considered, after accounting for social circumstances, such as weekends. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Clinically Significant Nonperfusion Areas on Widefield OCT Angiography in Diabetic Retinopathy.

Purpose: To investigate the distribution of clinically significant nonperfusion areas (NPAs) on widefield OCT angiography (OCTA) images in patients with diabetes. Design: Prospective, cross-sectional, observational study. Participants: One hundred and forty-four eyes of 114 patients with diabetes. Methods: Nominal 20 × 23 mm OCTA images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of en face images 20-mm (1614 pixels) in diameter centering on the fovea. The nonperfusion squares (NPSs) were defined as the 10 × 10 pixel squares without retinal vessels, and the ratio of eyes with the NPSs to all eyes in each square was referred to as the NPS ratio. The areas with probabilistic differences (APD) for proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) (APD[PDR] and APD[NPDR]) were defined as sets of squares with higher NPS ratios in eyes with PDR and NPDR, respectively. The P ratio (NPSs within APD[PDR] but not APD[NPDR]/all NPSs) was also calculated. Main Outcome Measures: The probabilistic distribution of the NPSs and the association with diabetic retinopathy (DR) severity. Results: The NPSs developed randomly in eyes with mild and moderate NPDR and were more prevalent in the extramacular areas and the temporal quadrant in eyes with severe NPDR and PDR. The APD(PDR) was distributed mainly in the extramacular areas, sparing the areas around the vascular arcades and radially peripapillary capillaries. The APD(PDR) contained retinal neovascularization more frequently than the non-APD(PDR) (P = 0.023). The P ratio was higher in eyes with PDR than in those with NPDR (P < 0.001). The multivariate analysis designated the P ratio (odds ratio, 8.293 × 107; 95% confidence interval, 6.529 × 102-1.053 × 1013; P = 0.002) and the total NPSs (odds ratio, 1.002; 95% confidence interval, 1.001-1.003; P < 0.001) as independent risk factors of PDR. Most eyes with NPDR and 4-2-1 rule findings of DR severity had higher P ratios but not necessarily greater NPS numbers. Conclusions: The APD(PDR) is uniquely distributed on widefield OCTA images, and the NPA location patterns are associated with DR severity, independent of the entire area of NPAs. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

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.

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.

Factors predicting the treatment frequency of ranibizumab injections during the second year in diabetic macular edema.

PURPOSE: To investigate the predictors of annual treatment frequency in the second year of pro re nata (PRN) intravitreal ranibizumab (IVR) injections for diabetic macular edema (DME). STUDY DESIGN: A retrospective study. METHODS: We reviewed 65 eyes of 60 patients with center-involved DME who received PRN IVR injections after 3 monthly loading doses. The central subfield thickness (CST) and qualitative findings were assessed on the spectral domain optical coherence tomography (SD-OCT) images. We then investigated whether the parameters at the baseline or at the 12-month visit were associated with treatment frequency in the second year. RESULTS: The number of ranibizumab injections decreased from 6 (4-8) during the first year to 2 (0-3) during the second year (P < .001). The injection numbers during the first year (ρ = 0.259, P = .037) but not during the second year (ρ = 0.152, P = .226) were modestly related to the logarithm of the minimum angle of resolution (logMAR) improvement at 24 months. Multivariate analyses revealed that the CST (ß = 0.336, P = .005) and hyperreflective walls in the foveal cystoid spaces (ß = 0.273, P = .020) at baseline were associated with the number of IVR injections during the second year. The treatment frequency during the second year was also related to the CST (ß = 0.266, P = .012), hyperreflective walls (ß = 0.394, P = .002), and cumulative doses of ranibizumab injections (ß = 0.294, P = .006) at the 12-month visit. CONCLUSIONS: The cumulative doses of ranibizumab injections, CST, and hyperreflective walls in the foveal cystoid spaces at the 12-month visit are designated predictors of the treatment frequency of ranibizumab injections during the second year in DME.

The intercapillary space spectrum as a marker of diabetic retinopathy severity on optical coherence tomography angiography.

Microcirculatory disturbance plays a pivotal role in the pathogenesis in diabetic retinopathy (DR). We retrospectively quantified the total counts and morphological features of intercapillary spaces, i.e., intercapillary areas and nonperfusion areas (NPAs), on swept-source optical coherence tomography angiography (SS-OCTA) images and to evaluate their associations with DR severity grades. We acquired 3 × 3 mm OCTA images in 75 eyes of 62 diabetic patients and 22 eyes of 22 nondiabetic subjects. In the en-face superficial images within the central 2 mm, the areas enclosed by retinal vessels were automatically detected. Their total numbers decreased in some eyes with no apparent retinopathy and most eyes with DR, which allowed us to discriminate diabetic subjects from nondiabetic subjects [area under the receiver operating characteristic curve (AUC) = 0.907]. The areas and area/perimeter ratios continuously increased in DR, indicating a continuum between healthy intercapillary areas and NPAs. The number of intercapillary spaces with a high area/perimeter ratio increased according to DR severity, which showed modest performance in discriminating moderate NPDR or higher grades (AUC = 0.868). These quantified parameters of intercapillary spaces can feasibly be used for the early detection of microcirculatory impairment and the diagnosis of referable DR.

A Modified Intrascleral Intraocular Lens Fixation Technique Using 27-Gauge Blunted Needles with Fewer Intraocular Manipulations.

A new method for intraocular lens (IOL) fixation in the scleral tunnel using two common 27G blunted needles and an ultrathin 30G needle with fewer intraocular manipulations was developed. Half-depth scleral flaps were prepared, and vertically angled sclerotomies were performed under each scleral flap, 2 mm from the limbs with a 20G microblade or a 26G needle. Two bent 27G blunted needles connected the sclerotomy and corneoscleral incisions. One haptic was inserted into this bent 27G blunted needle extraocularly and extruded through the sclerotomy site. Each haptic was inserted into the lumen of the preplaced ultrathin 30G needle and buried into the scleral tunnel. In this retrospective study, we reviewed the outcomes of this new technique in patients with at least 3 months' follow-up data. Iris capture of the IOL was not observed in any case, and IOL repositioning was not performed either. Astigmatism induced by intraocular aberration was almost as same as that with other methods. Our technique can be performed in any operation room without any extra instruments. This trial is registered with UMIN000044350.

Disproportion of lamellar capillary non-perfusion in proliferative diabetic retinopathy on optical coherence tomography angiography.

PURPOSE: To characterise the non-perfused areas (NPAs) in the superficial and deep capillary layers (sNPAs and dNPAs, respectively) in the posterior pole in proliferative diabetic retinopathy (PDR) on wide-field optical coherence tomography angiography (OCTA) images. METHODS: We retrospectively reviewed 104 eyes of 70 patients with PDR from whom wide-field swept source OCTA images were acquired. sNPAs and dNPAs were manually measured in each quadrant of the inner (1-3 mm diameter), intermediate (3-6 mm), and outer (6-10 mm) rings centred on the fovea. Two qualitative findings, that is, segmented NPAs and periarteriolar NPAs, were also compared. RESULTS: The dNPAs were greater than the sNPAs (p<0.001) in each subfield. The outer ring had higher rates of deep NPAs than did the intermediate ring in the superior, inferior and temporal quadrants (p=0.010, p=0.004 and p<0.001, respectively), whereas no differences were detected in the nasal quadrant (p=1.000). Similarly, sNPA rates were higher in the outer ring than in the intermediate ring in the inferior and temporal subfields (p=0.003 and p<0.001, respectively). In 45 eyes with extensive NPAs, there were modest correlations between the dNPAs in the nasal and temporal quadrants in the intermediate (ρ=0.341, p=0.026) and outer (ρ=0324, p=0.032) rings, whereas sNPAs exhibited no associations. Segmented NPAs were delineated more frequently in the superficial layer than in the deep layer (p<0.001). Periarteriolar NPAs were more frequent in the deep layer (p<0.001). CONCLUSIONS: Three-dimensional assessment of wide-field OCTA promotes a better understanding of the enigmatic disproportion of lamellar NPAs in the posterior pole in PDR.

Characteristics of Diabetic Capillary Nonperfusion in Macular and Extramacular White Spots on Optical Coherence Tomography Angiography.

Purpose: To compare the characteristics of macular and extramacular white spots on wide-field swept-source optical coherence tomography angiography (SS-OCTA) and optical coherence tomography (OCT) images in diabetic retinopathy (DR). Methods: We retrospectively reviewed 107 eyes of 64 patients with DR, of whom nominal 12 × 12 mm SS-OCTA images centered on the optic disc and ultrawide field photographs were acquired. White spots on fundus photographs corresponded to hyperreflective lesions in the superficial en-face OCT images, and the characteristics of these white spots were investigated. We compared such OCT findings with the vertical and horizontal extents of nonperfused areas (NPAs) on OCTA images. Results: We observed 136 white spots and corresponding hyperreflective lesions in 49 eyes. The hyperreflective lesions in the extramacular areas had greater areas (P < 0.001) and more frequently spanned from the nerve fiber layer to the outer plexiform layer (P < 0.001), while those in the macula were superficial. All of macular hyperreflective lesions were accompanied with nerve fiber layer defects, whereas only 18 (15.4%) of 117 extramacular lesions had them (P < 0.001). Comparative studies showed that most extramacular hyperreflective lesions corresponded to the NPAs in the whole layers on OCTA images, compared to the lamellar NPAs of the superficial layer in most of the macular lesions (P < 0.001). The NPAs extended to the peripheral side more frequently in the extramacular hyperreflective lesions compared with macular lesions (P < 0.001). Conclusions: This study proposed that most of the extramacular white spots may be discriminated from macular spots with respect to diabetic NPAs on OCTA images.