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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.

Sufian Elfandi,1 Sotaro Ooto,1 Manabu Miyata,1 Naoko Ueda-Arakawa,1 Yousif Subhi,1,2 Kenji Yamashiro,1 Hiroshi Tamura,1 Akio Oishi,1 Masayuki Hata,1 Nagahisa Yoshimura,1 Akitaka Tsujikawa1 1Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan; 2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Sotaro OotoDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine Email ohoto@kuhp.kyoto-u.ac.jpPurpose: 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.Keywords: age-related macular degeneration, aflibercept, pachychoroid neovasculopathy, choroidal thickness

Keratoconus is a common ocular disorder that causes progressive corneal thinning and is the leading indication for corneal transplantation. Central corneal thickness (CCT) is a highly heritable characteristic that is associated with keratoconus. In this two-stage genome-wide association study (GWAS) of CCT, we identified a locus for CCT, namely STON2 rs2371597 (P = 2.32 × 10−13), and confirmed a significant association between STON2 rs2371597 and keratoconus development (P = 0.041). Additionally, strong STON2 expression was observed in mouse corneal epithelial basal cells. We also identified SMAD3 rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM’s Watson question answering computer system (P = 0.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development., Yoshikatsu Hosoda et al. study the genetic basis for central corneal thickness (CCT) that is associated with keratoconus. They identify two susceptibility loci, STON2 rs2371597 and SMAD3 rs12913547, using two-step genome-wide association study (GWAS) and predictive analysis with IBM’s Watson question answering computer system, respectively.

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-naive 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

Purpose To explore novel prognostic factors associated with visual function and number of anti–vascular endothelial growth factor (VEGF) treatments in eyes with active myopic choroidal neovascularization (mCNV) using OCT angiography (OCTA). Design Prospective case series. Participants Twenty-eight treatment-naive eyes with active mCNV from 27 consecutive patients (mean age, 64.4 ± 11.1 years). Methods All eyes received through injection a single loading dose of intravitreal aflibercept (IVA), followed by additional IVA on a pro re nata (PRN) basis during the subsequent 12 months. At baseline, OCTA images of a 3 × 3-mm macular cube were acquired using an OCTA scanner. On binarized and skeletonized OCTA images of the outer retinal layer, OCTA-derived baseline parameters of mCNV—including lesion size, vessel density, vessel length density (VLD), vessel diameter index, and fractal dimension (FD)—were measured and evaluated for correlation with 12-month best-corrected visual acuity (BCVA) and number of additional injections. Main Outcome Measures The primary and secondary outcomes were BCVA 12 months after initial treatment and number of additional injections, respectively. Results There was no significant difference between baseline and 12-month BCVA (0.37 ± 0.30 and 0.30 ± 0.35 logarithm of the minimal angle of resolution, respectively; P = 0.23). The number of additional injections was 0.93 ± 1.02 (mean ± standard deviation). Baseline VLD, FD, and BCVA were correlated with 12-month BCVA (P = 0.02, r = 0.46; P = 0.02, r = 0.46; and P = 0.02, r = 0.45, respectively), and VLD also was correlated with the number of additional injections (P = 0.03, r = 0.42). Conclusions Exuberant mCNV, which is characterized by high VLD and FD derived using OCTA, is a predictor of poor visual outcomes after a single IVA injection followed by a PRN regimen. Only baseline VLD was correlated with the number of additional IVA injections, which indicates that this parameter could help to determine the optimal anti-VEGF treatment regimen for individual eyes with mCNV.

Purpose To investigate flow signal within subretinal hyperreflective material (SHRM) using optical coherence tomography angiography (OCTA) and its association with aflibercept treatment responses in treatment-naive neovascular age-related macular degeneration (nAMD). Design Prospective consecutive interventional case series. Methods Forty-four eyes of 44 patients with treatment-naive nAMD manifesting SHRM on OCT were studied. All patients underwent OCTA and received 3 monthly aflibercept injections. The intrinsic flow signals within SHRM were quantitatively analyzed using OCTA, and eyes were classified into the vascular and avascular SHRM groups. Results Of 44 eyes, 21 (47.7%) and 23 (52.3%) showed vascular SHRM and avascular SHRM, respectively. Compared with eyes with avascular SHRM, eyes with vascular SHRM showed higher rates of external limiting membrane (ELM) disruption owing to SHRM ( P = .015), classic choroidal neovascularization (CNV) (85.7% vs 26.1%, P = .87 × 10 −4 ), and intraretinal fluid ( P = .008) at baseline. After 3 aflibercept injections, 38 eyes (86.4%) showed dry macula despite persistent SHRM in 24 eyes (54.5%). Compared with the eyes with resolved SHRM, those with persistent SHRM showed higher rate of vascular SHRM (75.0% vs 15.0%, P = .86 × 10 −4 ), classic CNV ( P = .032), absence of polypoidal lesion ( P = .020), ELM disruption owing to SHRM ( P = .042), and intraretinal fluid ( P = .008). Dry macula after loading injections was significantly associated with SHRM resolution ( P = .025). Conclusions In nAMD, SHRM can be categorized as vascular and avascular by quantitative OCTA analysis. Vascular SHRM persisted after treatment and was associated with failure to achieve dry macula, suggesting that vascular SHRM is predictive of lower response to anti-VEGF therapy.

The recently emerged pachychoroid concept has changed the understanding of age-related macular degeneration (AMD), which is a major cause of blindness; recent studies attributed AMD in part to pachychoroid disease central serous chorioretinopathy (CSC), suggesting the importance of elucidating the CSC pathogenesis. Our large genome-wide association study followed by validation studies in three independent Japanese and European cohorts, consisting of 1546 CSC samples and 13, 029 controls, identified two novel CSC susceptibility loci: TNFRSF10A-LOC389641 and near GATA5 (rs13278062, odds ratio = 1.35, P = 1.26 × 10−13; rs6061548, odds ratio = 1.63, P = 5.36 × 10−15). A T allele at TNFRSF10A-LOC389641 rs13278062, a risk allele for CSC, is known to be a risk allele for AMD. This study not only identified new susceptibility genes for CSC, but also improves the understanding of the pathogenesis of AMD., 特殊な網膜剥離の発症に関わる遺伝子変異を発見 --中心性漿液性脈絡網膜症のゲノムワイド関連解析--. 京都大学プレスリリース. 2019-12-13.

Purpose To investigate the choroidal vascular structural changes in eyes with central serous chorioretinopathy (CSC) by using swept-source optical coherence tomography (SS-OCT). Design Prospective cross-sectional study. Methods We prospectively examined 40 eyes of 34 consecutive patients with CSC. Three-dimensional choroidal images of the macular area, covering 3 × 3 mm and 6 × 6 mm, were obtained with SS-OCT. En face images of the microvasculature of the inner choroid and large choroidal vessel layers were converted to binary images. Choroidal vascular areas were analyzed quantitatively using the binary images. Results The choroidal vascular area was larger in eyes with CSC (the microvasculature of the inner choroid: 53.4% ± 2.4%, P = .028; 3 × 3-mm large choroidal vessels: 66.9% ± 7.1%, P P P = .038) and in diffuse retinal pigment epitheliopathy (52.9% ± 2.6%, P = .042). The subfoveal choroidal thickness was significantly associated with the choroidal vascular area at the level of large choroidal vessels ( P Conclusions Increased choroidal vascular area was observed in the whole macula area in eyes with CSC. This finding suggests that CSC may originate from a choroidal circulatory disturbance.

To assess whether optical coherence tomography angiography (OCTA) can be used as an alternative to conventional fundus fluorescein angiography (FFA) for the detection of myopic choroidal neovascularization (CNV).Validity and reliability analysis.Twenty-eight eyes of 26 consecutive Japanese patients with exudative lesions associated with pathologic myopia were included in this institutional study. Myopic CNV was detected in 23 eyes of 22 patients; 5 eyes exhibited simple hemorrhage. The main outcome measure was CNV detection by OCTA and FFA. The CNV area was individually measured by FFA and OCTA. Intraclass correlation coefficients (ICCs) for the CNV area, independently measured by 2 investigators using OCTA and FFA, were determined.OCTA images with sufficient quality for CNV assessment were obtained for 17 eyes with CNV and 4 without. FFA alone detected CNV in all 17 eyes, while OCTA alone detected CNV in 16 (94.1%). The 1 eye for which CNV was not detected by OCTA exhibited a 0.01 mm(2) area on FFA. Both FFA and OCTA did not detect CNV in eyes with simple hemorrhage. The mean CNV areas on FFA and OCTA were 0.59 ± 0.56 mm(2) and 0.51 ± 0.55 mm(2), respectively; the 2 values were significantly correlated (P.001, r = .86). The ICC (2, 1) values for FFA and OCTA were 0.944 and 0.997, respectively.Our results indicate that OCTA can detect most myopic CNVs if high-quality images are acquired and can preclude the requirement for FFA in these settings.

Purpose To compare the efficacy of photodynamic therapy (PDT) in eyes with polypoidal choroidal vasculopathy (PCV) associated with and without pachychoroid phenotypes (pachychoroid PCV and nonpachychoroid PCV, respectively). Design Retrospective chart review. Participants Patients previously diagnosed with PCV and initially treated with PDT. Methods Patients were classified as having pachychoroid- or nonpachychoroid-driven conditions. The long-term visual outcome and its associated factors were investigated. Main Outcome Measures Visual acuity (VA) outcomes at 1, 2, 3, 4, and 5 years after initial PDT in pachychoroid and nonpachychoroid PCV. Results Of the 158 eyes, 88 (55.7%) met the criteria for pachychoroid PCV; 70 (44.3%) did not (nonpachychoroid PCV). In cases of pachychoroid PCV, VA improved significantly at 1 year (P = 0.042) and maintained baseline level at 5 years (P = 0.38). By contrast, VA continued to deteriorate in the nonpachychoroid PCV group during the follow-up period and had already declined significantly by the second year (P = 0.022, compared with baseline). Despite no difference in baseline VA between pachychoroid and nonpachychoroid PCV groups (P = 0.11), the VA at 5 years was significantly better in the pachychoroid PCV group compared with the nonpachychoroid PCV group (0.54±0.47 vs. 0.93±0.63, respectively; P = 0.23 × 10–3). The incidence of massive submacular hemorrhage (SMH) or vitreous hemorrhage (VH) was not different between groups at 5 years (P = 0.67), and their occurrence was associated with decreased VA in both the nonpachychoroid and pachychoroid PCV groups (coefficient β, 0.361 and 0.481; P = 0.59 × 10–3 and P Conclusions Five years after PDT treatment, VA was maintained at the baseline level in the pachychoroid PCV group but not in the nonpachychoroid PCV group. Massive SMH or VH during the follow-up period affected the final visual outcomes in both conditions.

Intravitreal injections of anti-vascular endothelial growth factor agents such as ranibizumab and aflibercept are the first-line treatment for neovascular age-related macular degeneration (AMD). However, data about long-term outcome in real-world clinical practice is scarce. We recruited 98 AMD patients and investigated four-year visual outcome. During the four years, 25 patients dropped out. The survivors received 7.0 ± 0.1 injections during the first year and 8.0 ± 7.4 injections in the following three years. The logarithm of minimum angle of resolution (logMAR) at baseline, year one, and year four was 0.28, 0.14 (P = 0.033), and 0.22 (P = 0.697), respectively. The gain of vision was not different among AMD subtypes (typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation; P = 0.513) Among the investigated factors, the presence of external limiting membrane (ELM), the absence of vitreoretinal adhesion, and thicker choroid at baseline were associated with better logMAR values at year four (coefficient beta = −0.388, 0.201, and −0.001; P = 7.34 × 10−6; 0.01, and 0.028, respectively). In the present study, vision was retained at baseline level after the four-year treatment with aflibercept. The status of ELM, vitreoretinal adhesion, and choroidal thickness were predictive factors for final vision.

Background/aimsTo evaluate the 5-year visual and anatomical outcomes after anti-vascular endothelial growth factor (VEGF) therapy alone or in combination with photodynamic therapy (PDT), followed by pro re nata (PRN) anti-VEGF therapy with or without PDT, for polypoidal choroidal vasculopathy (PCV).MethodsThis retrospective, observational study included 61 consecutive patients with treatment-naïve symptomatic PCV who were followed for 5 years. Twenty eyes (20 patients) initially received PDT and intravitreal injection of ranibizumab (IVR), followed by a PRN regimen of anti-VEGF therapy with or without PDT (combination group), while 41 eyes (41 patients) initially received only IVR every 3 months, followed by a PRN regimen of anti-VEGF monotherapy (IVR group). Macular atrophy including the fovea was confirmed using colour fundus photography and spectral-domain optical coherence tomography.ResultsIn both groups, the visual acuity (VA) at 1 year was better than the baseline VA, whereas the 3-year, 4-year and 5-year VA values were similar to the baseline VA. There was no significant difference in the 5-year VA, 5-year central retinal thickness and incidence of macular atrophy between the two groups (p=0.63, 0.72 and 0.06, respectively). In the combination group, the 5-year VA was correlated with the 5-year incidence of macular atrophy (p=0.02, r=0.51).ConclusionsA PRN regimen for PCV may have a limited effect for the long-term maintenance of improved VA. Macular atrophy may occur more frequently with combination therapy and is possibly associated with the 5-year VA. Thus, combination therapy should be carefully selected for patients susceptible to macular atrophy.

To determine the association between reflectivity levels in foveal cystoid spaces on optical coherence tomography images and the course of the logarithm of the minimum angle of resolution (logMAR) after triamcinolone acetonide treatment for diabetic macular edema.We retrospectively reviewed 58 consecutive eyes treated with an intravitreal or sub-Tenon's injection of triamcinolone acetonide for diabetic macular edema. The foveal cystoid spaces within central 1 mm were circumscribed, followed by measurement of optical coherence tomography reflectivity. The correlation between the reflectivity and visual outcome was investigated.The optical coherence tomography reflectivity levels in foveal cystoid spaces increased at 1 month after treatment, but not at 3 months or 6 months. The preoperative reflectivity levels were correlated negatively with logMAR changes from 1 month to 6 months and from 3 months to 6 months but not with logMAR at individual time points compared with the preoperative logMAR. The changes in foveal thickness from 1 month to 6 months were correlated negatively with the baseline reflectivity and positively with logMAR changes from 1 month to 6 months and from 3 months to 6 months.Lower optical coherence tomography reflectivity in foveal cystoid spaces was associated with the rebound in macular thickening and visual deterioration after triamcinolone acetonide treatment for diabetic macular edema.

To investigate the incidence rate and risk factors for development of retinal pigment epithelial (RPE) atrophy during anti-vascular endothelial growth factor (anti-VEGF) treatment for retinal angiomatous proliferation.This study included 46 eyes with treatment-naive retinal angiomatous proliferation. All patients were treated with ranibizumab or aflibercept injections. Color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy diagnosis. Baseline characteristics and gene polymorphisms of ARMS2 A69S, and CFH I62V were analyzed for association with development and progression of RPE atrophy.Among 21 eyes treated with ranibizumab without preexisting RPE atrophy at baseline, 5 eyes (23.8%) developed RPE atrophy at 12 months. Among 20 eyes treated with aflibercept without preexisting RPE atrophy at baseline, 10 eyes (50.0%) developed RPE atrophy at 12 months. Refractile drusen at baseline was associated with RPE atrophy development at 12 months (P = 0.014), and the progression rate of RPE atrophy area was negatively correlated with subfoveal choroidal thickness at baseline (R = -0.595, P = 0.019). Gene polymorphisms were not associated with RPE atrophy.Retinal pigment epithelial atrophy developed in 36.6% during 12 months after anti-VEGF treatment for retinal angiomatous proliferation. The presence of refractile drusen at baseline was identified as a novel significant risk factor for RPE atrophy development.

[Purpose]To compare the 2-year results after photodynamic therapy (PDT) alone and PDT combined with intravitreal injections of bevacizumab and triamcinolone acetonide (triple therapy) for polypoidal choroidal vasculopathy (PCV). [Methods]We retrospectively reviewed the medical records of 40 consecutive patients (40 eyes) with subfoveal PCV. Of these 40 eyes, 16 were treated with PDT alone and 24 were treated with triple therapy. [Results]The change in visual acuity in the triple therapy group was significantly better than that in the PDT group (P

To investigate the incidence rate, risk factors, and final outcomes of patients with age-related macular degeneration (AMD) who have experienced vision loss despite periodic aflibercept treatment. Subjects with treatment-naive AMD were prospectively recruited and treated with three monthly injections followed by two monthly injections of aflibercept. The incidence rate and risk factors of more than two lines of vision loss at any visit were investigated. We included 196 eyes of 196 patients. Vision loss was observed in 16 patients (8.2%). Eleven of 16 patients developed vision loss during the initial 3 months (68.8%). Vision loss remained in 11 eyes (68.8%) at the final visit. The maximum pigment epithelium detachment (PED) height (odds ratio = 1.46 for a 100-μm increase in the PED height) and disruption of the external limiting membrane (odds ratio = 4.45) were identified as risk factors for developing vision loss on logistic regression analysis. The incidence rate of vision loss during aflibercept treatment was relatively low. Identifying high-risk patients, those with a high PED height and disruption of the external limiting membrane, would be helpful in ensuring appropriate informed consent before treatment. Further studies are needed to establish optimal treatment for these patients.

To quantify the area of photoreceptor damage surrounding geographic atrophy (GA) and evaluate the relationship between structural abnormalities and retinal function in eyes with GA.Prospective cross-sectional study.Twenty-five eyes of 25 patients with GA associated with age-related macular degeneration underwent a full ophthalmologic examination, including spectral-domain optical coherence tomography (SDOCT), fundus autofluorescence (FAF), and microperimetry. ImageJ software was used to quantify the disruption of the ellipsoid zone on SDOCT images. Hypofluorescent areas of the FAF images indicated areas of retinal pigment epithelium (RPE) loss. Areas of interest graded by SDOCT (photoreceptor damage) and FAF (RPE loss) were registered with microperimetry within a 6-mm circle centered on the fovea.The mean area of photoreceptor damage was 7.69 ± 5.36 mm(2), which was significantly greater than the mean area of RPE loss (4.57 ± 4.07 mm(2), P.001). The average retinal sensitivity of the area with photoreceptor damage outside the area of RPE loss was lower than that of the area without photoreceptor damage (6.57 ± 4.13 dB vs 11.27 ± 3.78 dB, P.001). The area of photoreceptor damage surrounding the area of RPE loss was larger in eyes with pseudodrusen than in eyes without pseudodrusen (4.96 mm(2) vs 1.91 mm(2), P = .008). The only significant predictor of decreased retinal sensitivity was the area of the photoreceptor damage (P.001).Widespread photoreceptor damage surrounding sites of RPE loss occurred in eyes with GA, and it correlated with visual function. Evaluation of photoreceptor damage surrounding sites of RPE loss using OCT is important in patients with GA associated with AMD.

[Purpose]To study the retinal structural changes associated with submacular hemorrhage due to exudative age-related macular degeneration (AMD) and their relationships with visual prognosis. [Methods]We retrospectively reviewed the medical records of 31 consecutive patients (31 eyes) with visual impairment due to an acute submacular hemorrhage associated with typical AMD (10 eyes) or polypoidal choroidal vasculopathy (21 eyes). [Results]Optical coherence tomography (OCT) revealed that submacular hemorrhage exhibited intense hyperreflectivity beneath the neurosensory retina and often seemed to infiltrate it. In the OCT sections, mild to moderate amorphous hyperreflectivity and/or hyperreflective dots were observed within the neurosensory retina, resulting in the loss of the junctions between the inner (IS) and outer (OS) segments of the photoreceptors. Of the 31 eyes, the foveal IS/OS line could be seen incompletely in 12 eyes and was totally absent in 16 eyes. The initial integrity of the foveal photoreceptor layer was correlated with the final visual acuity; the initial detection of the IS/OS just beneath the fovea was correlated with good final visual acuity (r = 0.375, p = 0.038). [Conclusion]As a hallmark of integrity of the foveal photoreceptor layer, the initial detection of the IS/OS just beneath the fovea may predict good visual outcomes.

[Background]: We aimed to study the retinal morphological findings associated with exudative age-related macular degeneration (AMD) and their association with visual prognosis. [Methods]: We retrospectively reviewed the medical records of 96 consecutive patients (96 eyes) with exudative AMD. Retinal structural changes were examined using optical coherence tomography (OCT). [Results]: Initial OCT examination showed cystoid macular edema in 18 eyes (18.8%), fibrin exudate in 56 eyes (58.3%), and hyperreflective foci within the neurosensory retina in 78 eyes (81.3%). Upon initial examination, an external limiting membrane (ELM) line was detected under the fovea in 64 eyes (66.7%). Using Pearson’s correlation analyses, final visual acuity (VA) was correlated with initial VA (r = 0.61, p

Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19.5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p = 5.1 × 10−5) and showed a greater subfoveal choroidal thickness (p = 3.4 × 10−14). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0.029), CFH rs800292 (p = 0.013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 3.8 × 10−3). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studies.

Purpose To investigate the difference in intraocular vascular endothelial growth factor (VEGF) concentration between pachychoroid neovasculopathy and neovascular age-related macular degeneration (nAMD) and its associations with responses to three monthly anti-VEGF injections as an initial treatment for the two conditions. Methods This study included nine eyes with treatment-naive pachychoroid neovasculopathy and 21 eyes with treatment-naive nAMD. Before the initial intravitreal anti-VEGF injection, aqueous humor samples were collected and the concentration of VEGF was measured using enzyme-linked immunosorbent assay. The concentration was compared between the two conditions, and its associations with responses to anti-VEGF therapy were investigated. Results The mean VEGF concentration in pachychoroid neovasculopathy was significantly lower than that in nAMD (63.4 ± 17.8 pg/ml and 89.8 ± 45.0 pg/ml, respectively; P = 0.035). The VEGF concentration was associated with the presence or absence of drusen (β = 0.503, P = 0.004). After anti-VEGF therapy, 6 (66.7%) of 9 eyes with pachychoroid neovasculopathy and 17 (81.0%) of 21 eyes with nAMD achieved dry macula (P = 0.640). Dry macula at 3 months and 12 months was significantly associated with a low VEGF concentration in pachychoroid neovasculopathy (P = 0.013 and P = 0.042, respectively), but not in nAMD (P = 0.108 and P = 0.219). Conclusions The mean VEGF concentration in pachychoroid neovasculopathy was lower than that in nAMD, suggesting that the way in which VEGF is involved in angiogenesis may differ between pachychoroid neovasculopathy and nAMD.

Purpose To investigate the efficacy of periodic injection of aflibercept in each subtype of age-related macular degeneration (AMD) and to explore the predictive factors for visual outcome in clinical settings. Design Prospective nonrandomized interventional case series. Methods Patients with AMD were recruited and were administered aflibercept injections once a month for 3 months followed by once every 2 months for 8 months. The logarithm of the minimal angle of resolution (logMAR) at 12 months and improvement of vision from baseline were compared among polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and typical AMD. Regression rate of polypoidal lesions was assessed. We also performed regression analysis with logMAR at 12 months as the dependent variable. Results The study sample consisted of 98 patients: 46 had typical AMD, 42 had PCV, and 10 had RAP. Mean logMAR improved from 0.36 to 0.21 in 12 months. While there was no difference in visual improvement between typical AMD and PCV, final logMAR was better in PCV (0.32 ± 0.09 vs 0.08 ± 0.04, P = .016). Thirty-nine PCV patients underwent follow-up angiography, and regression of polyps was observed in 27 cases (69.2%). Multiple regression analysis showed that the presence of external limiting membrane (ELM), smaller greatest linear dimension, and the presence of polypoidal lesion were associated with better visual outcome (R2 = 0.53, P = 2.73 × 10−14). Conclusions Periodic injection of aflibercept is effective for PCV as well as for typical AMD. The statuses of ELM, greatest linear dimension, and polypoidal lesion are predictive for visual outcome.

To evaluate visual and anatomic outcomes in response to the conversion of treatment in patients with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) refractory to previous treatment. We also investigated the effect of genetic factors. We recruited patients with AMD or PCV refractory to ranibizumab and initiated aflibercept treatment. Changes in the logarithm of minimum angle of resolution (logMAR) and central retinal thickness (CRT) measured using optical coherence tomography (OCT) 6 months after the conversion were compared between the AMD and PCV groups. We also genotyped each patient for the ARMS2 A69S, CFH Y402H, and I62V alleles, and investigated the association between genotype and treatment response. Mean age of the participants was 75.6 ± 8.0 years. There were 15 patients with AMD and 26 patients with PCV. While PCV patients gained about 1 line of vision (0.40 ± 0.37 to 0.31 ± 0.40, P = 0.003), AMD patients did not show significant improvement (0.41 ± 0.37 to 0.42 ± 0.39, P = 0.699) despite the decrease in CRT (202.1 ± 113.7 to 131.2 ± 55.7 μm, P = 0.003). The prevalence of dry retina after treatment was higher among PCV patients (80.8 vs 46.7 %, P = 0.024). There was no significant difference between patients with risk and non-risk alleles for ARMS2 A69S, CFH Y402H, and I62V. In AMD or PCV patients refractory to ranibizumab, switching to aflibercept is generally effective regardless of patient genotype. PCV patients may benefit more significantly than AMD patients.

PURPOSE: To investigate the correlation between visual outcomes and preoperative hyperreflective foci in the outer retinal layers seen on spectral domain optical coherence tomography images in eyes that underwent vitrectomy for diabetic macular edema. METHODS: We retrospectively reviewed 32 consecutive eyes that underwent vitrectomy for diabetic macular edema. Ten eyes had accumulated or many hyperreflective foci in the outer retinal layers preoperatively; 22 eyes did not have the pathology. The logarithm of the minimum angle of resolution and the junction between inner and outer segments were studied in the groups. RESULTS: Logarithm of the minimum angle of resolution was significantly better in eyes without hyperreflective foci than in those with hyperreflective foci at 3 months and 6 months, and the last visit (P = 0.029, 0.010, and

To study the relationship between retinal vessel diameter and qualitative and quantitative evaluations on spectral-domain optical coherence tomography in patients with diabetic macular edema.One hundred and eight consecutive eyes of 80 patients, with clinically significant macular edema underwent optical coherence tomography and color fundus photography. The authors evaluated the retinal thickness of the Early Treatment Diabetic Retinopathy Study grid and foveal pathomorphologies including cystoid macular edema and serous retinal detachment on the optical coherence tomography images. The diameters of the superotemporal or inferotemporal retinal vessels originating from the optic disk were measured using a computer-assisted technique.The mean diameters of the superotemporal and inferotemporal venules were larger in eyes with diabetic macular edema than in healthy eyes. The mean diameter of the temporal venules but not the arterioles was associated with perifoveal thickening in the inferior subfield in eyes with diabetic macular edema (P = 0.014). Although the retinal thickening in the central subfield was not correlated with the diameters of the retinal vessels, eyes with foveal serous retinal detachment had larger mean diameters of superotemporal and inferotemporal venules than those without serous retinal detachment (P0.001).The mean diameters of the superotemporal and inferotemporal venules were significantly associated with foveal serous retinal detachment in diabetic macular edema.

To evaluate the effect of macular reticular pseudodrusen on retinal function using multiple imaging methods.Prospective cross-sectional study.Thirteen eyes with reticular pseudodrusen, but without any other macular abnormality or glaucoma, and 20 normal eyes were evaluated. All subjects underwent color fundus photography, infrared reflectance (IR), fundus autofluorescence (FAF), and microperimetry.The similarity in the number of reticular pseudodrusen was evaluated through inter-observer intraclass correlation coefficients, which ranged from 0.852-0.944. IR could detect reticular pseudodrusen within the center circle area in 12 eyes, whereas blue-channel fundus photography and FAF could only detect these lesions in 1 and 3 eyes, respectively. The number of reticular pseudodrusen correlated among the different imaging modalities (P.001 for all) for all areas of the macula, except the center. The mean retinal sensitivity in eyes with reticular pseudodrusen was lower in all areas of the macula, compared with normal eyes (P.001 for all). The number of reticular pseudodrusen correlated with retinal sensitivity in all areas by IR imaging (P = .003, P.001, P = .003 for center, inner ring, outer ring, respectively), in the inner and outer rings by blue-channel fundus photography (P.001 for both), and in the inner and outer rings by FAF (P.001 and P = .001, respectively).Although multiple imaging modalities are capable of quantifying reticular pseudodrusen, IR appears to have the best ability to do so as compared to blue-channel photography and FAF. The distribution and number of reticular pseudodrusen lesions are closely associated with retinal sensitivity.

Purpose To identify reticular pseudodrusen (RPD) in age-related macular degeneration using multiple imaging modalities, including the blue channel image of fundus photography, infrared reflectance (IR), fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and spectral-domain optical coherence tomography (SD-OCT), and to compare the sensitivities and specificities of these modalities for detecting RPD. Methods This study included 220 eyes from 114 patients with newly diagnosed age-related macular degeneration. Patients underwent fundus photography, IR, fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and SD-OCT in both eyes. Eyes were diagnosed with RPD if they showed reticular patterns on at least two of the seven imaging modalities. Results Thirty-seven eyes were diagnosed with RPD. However, SD-OCT and IR had the highest sensitivity (94.6%), and at the same time, SD-OCT had a high specificity (98.4%). The blue channel of color fundus photography, confocal blue reflectance, and indocyanine green angiography had a specificity of 100% but had lower sensitivity than that of SD-OCT and IR. Conclusion For detecting RPD, IR and SD-OCT had the highest sensitivity. Although SD-OCT had the highest sensitivity and specificity, RPD detection should be confirmed using more than one modality for increased accuracy.

Purpose To use adaptive optics scanning laser ophthalmoscopy (AO-SLO) to quantify cone loss ratio in the foveola in order to assess foveal cone status and to investigate relationships between foveal structural abnormalities and visual function in patients with macular hole (MH) after surgery. Methods We evaluated 10 normal eyes of 10 healthy volunteers and 19 eyes of 18 patients in whom anatomically successful MH closure had been performed. All subjects underwent a comprehensive ophthalmologic examination that included measurements of spectral-domain optical coherence tomography and AO-SLO. Results On AO-SLO regular cone mosaic was seen in all normal eyes whereas dark regions suggesting cone loss were seen in all eyes after MH repair. Visual acuity was better in eyes without dark regions at the center of the fovea than in eyes with them (P = 0.001). Cone loss ratio in the foveola correlated with postoperative visual acuity (P

To compare pathologic changes in the photoreceptors of eyes with idiopathic macular telangiectasia types 1 and 2 using adaptive optics scanning laser ophthalmoscopy (AO-SLO).Prospective cross-sectional study.Eleven eyes with idiopathic macular telangiectasia type 1, 14 eyes with type 2, and 10 normal eyes underwent a full ophthalmologic examination, spectral-domain optical coherence tomography (SD-OCT), and imaging with an original prototype AO-SLO system. All eyes with idiopathic macular telangiectasia were examined with fluorescein angiography (FA), confocal blue reflectance, and microperimetry.Compared with normal eyes (29 017 ± 5507 cones/mm(2)), those with idiopathic macular telangiectasia type 1 had significantly lower cone density on the temporal side (18 427 ± 4908 cones/mm(2), P = .010). The FA leakage area (5.90 ± 3.23 mm(2)) was larger than the dark regions (2.45 ± 2.40 mm(2)) on AO-SLO (P = .003)-which were observed only in the FA leakage area. Compared with normal eyes, those with idiopathic macular telangiectasia type 2 had significantly lower cone density in all areas (P.05 for all). Patchy dark regions were also seen in areas without FA abnormalities in 12 eyes. Higher mean retinal sensitivity correlated with greater mean cone density 0.5 mm from the center of the fovea (type 1: P = .010; type 2: P.001).Idiopathic macular telangiectasia type-specific differences in the distribution of photoreceptor abnormalities were shown in the AO-SLO images. For both idiopathic macular telangiectasia types 1 and 2, visual impairment was associated with cone damage.

PURPOSE. To measure the inner and outer retinal thicknesses on spectral-domain optical coherence tomography (SD-OCT) and evaluate their association with logMAR after vitrectomy for diabetic macular edema (DME). METHODS. In this retrospective case series, there were 55 consecutive eyes with DME for which vitrectomy was performed. The total retinal thickness, the inner thickness (from the innermost of the retina to the inner nuclear layer), and the outer thickness (from the outer plexiform layer to the retinal pigment epithelium) in the parafoveal subfields were measured manually, and the association with logMAR was evaluated. RESULTS. The total retinal thicknesses in the central, nasal, and inferior subfields were significantly (r ¼ 0.37, P ¼ 0.005; r ¼ 0.29, P ¼ 0.032; r ¼ 0.33, P ¼ 0.015, respectively) associated with the baseline logMAR; no subfield thickness was correlated with the logMAR at the final visit. However, segmentational analysis showed that the outer retinal thickness of the temporal subfield was associated with disruption of the junction between the inner and outer segments at the fovea (P ¼ 0.021 and P ¼ 0.005) and negatively correlated with the logMAR (r ¼� 0.37, P ¼ 0.006 and r ¼� 0.28, P ¼ 0.042) at the 6-month and final visit. The inner thickness of the nasal subfield did not change after vitrectomy compared with the other subfields and the outer thickness of all subfields in the parafoveal area; the baseline nasal total thickness was correlated most significantly with the logMAR (r ¼ 0.40, P ¼ 0.002 and r ¼ 0.37, P ¼ 0.006) at the 6-month and final visits. CONCLUSIONS. Segmentational analysis provided useful information for considering the prognosis and pathogenesis after vitrectomy for DME. (Invest Ophthalmol Vis Sci. 2012; 53:6668‐6674) DOI:10.1167/iovs.12-9934

To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO).Prospective cross-sectional study.Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system.The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P.001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P.001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017).AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function.

PURPOSE To assess photoreceptor structure in macular microholes by using adaptive optics scanning laser ophthalmoscopy (AO-SLO) and spectral-domain optical coherence tomography (SD-OCT) and compare with visual acuity. METHODS Fourteen eyes from 12 patients with macular microholes underwent a full ophthalmologic examination and imaging with a fundus camera, SD-OCT, and an original prototype AO-SLO system at each visit. RESULTS All eyes had a cone outer segment tip line disruption and a normal retinal pigment epithelium line on SD-OCT images. Adaptive optics scanning laser ophthalmoscopy revealed foveal cone disruption (13 eyes, round or oval; 1 eye, T-shaped) in all eyes. Cone disruption area (mean = 14,805 ± 9120 μm(2); range, 3495-35,901 μm(2)) positively correlated with logMAR visual acuity at the first visit (P = 0.015, rs = 0.679). During the follow-up period, cone disruption area increased in two eyes, was stable in seven eyes, and decreased in five eyes. At the last visit, cone disruption area (mean = 8717 ± 7432 μm(2); range, 0-25,746 μm(2)) also positively correlated with logMAR visual acuity (P = 0.035, rs = 0.610). In one patient with bilateral microholes and no apparent vitreous traction, lesion size gradually increased. Cone disruption area decreased and visual acuity improved following oral prednisone therapy. CONCLUSIONS Cone disruption occurs in eyes with macular microholes and a larger cone disruption area translates into a poorer visual acuity. Macular microholes, which are commonly observed as foveal cone inner and outer segment disruptions, may occur in eyes with or without vitreofoveal traction.

PURPOSE To integrate parameters on spectral-domain optical coherence tomography (SD-OCT) in diabetic retinopathy (DR) based on the self-organizing map and objectively describe the macular morphologic patterns. METHODS A total of 336 consecutive eyes of 216 patients with DR for whom clear SD-OCT images were available were retrospectively reviewed. Eleven OCT parameters and the logarithm of the minimal angle of resolution (logMAR) were measured. These multidimensional data were analyzed based on the self-organizing map on which similar cases were near each other according to the degree of their similarities, followed by the objective clustering. RESULTS Self-organizing maps indicated that eyes with greater retinal thickness in the central subfield had greater thicknesses in the superior and temporal subfields. Eyes with foveal serous retinal detachment (SRD) had greater thickness in the nasal or inferior subfield. Eyes with foveal cystoid spaces were arranged to the left upper corner on the two-dimensional map; eyes with foveal SRD to the left lower corner; eyes with thickened retinal parenchyma to the lower area. The following objective clustering demonstrated the unsupervised pattern recognition of macular morphologies in diabetic macular edema (DME) as well as the higher-resolution discrimination of DME per se. Multiple regression analyses showed better association of logMAR with retinal thickness in the inferior subfield in eyes with SRD and with external limiting membrane disruption in eyes with foveal cystoid spaces or thickened retinal parenchyma. CONCLUSIONS The self-organizing map facilitates integrative understanding of the macular morphologic patterns and the structural/functional relationship in DR.

Purpose To study the prevalence and 3-dimensional (3-D) tomographic features of focal choroidal excavations in eyes with central serous chorioretinopathy (CSC) using swept-source optical coherence tomography (OCT). Design Prospective, cross-sectional study. Methods We examined 116 consecutive eyes with CSC with a prototype 3-D swept-source OCT. 3-D images of the shape of the macular area, covering 6 × 6 mm 2 , were reconstructed by segmentation of the outer surface of the retinal pigment epithelium (RPE). Results The 3-D swept-source OCT detected focal choroidal excavations in 9 eyes (7.8%). The 3-D scanning protocol, coupled with en face scans, allowed for clear visualization of the excavation morphology. In 5 eyes with focal excavations, unusual choroidal tissue was found beneath the excavation, bridging the bottom of the excavation and the outer choroidal boundary. Additionally, 3 of those 5 eyes showed a suprachoroidal space below the excavation, as if the outer choroidal boundary is pulled inward by this bridging tissue. The focal choroidal excavations were located within fluorescein leakage points and areas of choroidal hyperpermeability. Eyes with focal choroidal excavations were more myopic (−4.42 ± 2.92 diopters) than eyes without excavations (−0.27 ± 1.80 diopters, P = .001). Subfoveal choroidal thickness was significantly thinner (301.3 ± 60.1 μm) in eyes with focal excavations than in eyes without the excavations (376.6 ± 104.8 μm, P = .036). Conclusions Focal choroidal excavations were present in 7.8% of eyes with CSC. In these eyes, focal choroidal excavations may have formed from RPE retraction caused by focal scarring of choroidal connective tissue.

To survey the prevalence of reticular pseudodrusen in late age-related macular degeneration (AMD) using multiple imaging methods, and to investigate the association between reticular pseudodrusen and polymorphisms in complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genes.Retrospective case series.This study included 216 consecutive patients with late AMD (typical AMD, polypoidal choroidal vasculopathy [PCV], retinal angiomatous proliferation [RAP], or geographic atrophy). Eyes were assessed for reticular pseudodrusen using the blue channel of color fundus photography, infrared reflectance, fundus autofluorescence, and spectral-domain optical coherence tomography. The major AMD-associated single nucleotide polymorphisms (CFH Y402 rs1061170, CFH I62V rs800292, and ARMS2 A69S rs10490924) were genotyped.Forty-nine eyes of 30 patients had a reticular pattern in ≥2 imaging modalities and were diagnosed with reticular pseudodrusen. Of these, 16 had bilateral late AMD, whereas 32 of 186 patients without reticular pseudodrusen had bilateral late AMD (P.001). The prevalence of reticular pseudodrusen was 83% in RAP, 50% in geographic atrophy, 9% in typical AMD, and 2% in PCV. The frequency of the T allele in ARMS2 A69S in patients with and without reticular pseudodrusen was 78.6% and 59.9%, respectively (P=.007).The prevalence of reticular pseudodrusen was low in PCV cases. About 50% of patients with reticular pseudodrusen had bilateral late AMD. The connection of ARMS2 risk allele and reticular pseudodrusen was confirmed in a Japanese population.

PURPOSE To investigate the relationship between the cystoid spaces in the outer plexiform layer (OPL) and the characteristics of the photoreceptors beneath the cystoid spaces in patients with diabetic macular edema (DME). METHODS In this observational cross-sectional study, 123 eyes of 96 consecutive patients with clinically significant macular edema were retrospectively reviewed. The characteristics of the photoreceptors on optical coherence tomography (OCT) images represented by the external limiting membrane (ELM) and the junction between inner and outer segments (IS/OS), and their association with the overlying cystoid spaces were investigated. RESULTS The areas beneath the cystoid spaces in the OPL had a longer transverse length of disrupted or faint IS/OS and disrupted ELM lines than those without cystoid spaces (P < 0.001, P < 0.001, and P = 0.009). The IS/OS lines beneath the cystoid spaces had higher reflectivity than those in areas without cystoid spaces (P < 0.001). Enlarged cystoid spaces extending from the inner nuclear layer to the OPL were associated with disrupted IS/OS or ELM but not faint IS/OS (P < 0.001, P < 0.001, and P = 0.467). The transverse length of disrupted IS/OS at the fovea was correlated with the logarithm of the minimum angle of resolution (logMAR) more than the association between foveal thickness and logMAR (r = 0.49, P < 0.001 vs. r = 0.28, P = 0.002). The ELM descended to the RPE more frequently in eyes with single-lobulated fluorescein pooling in the foveal avascular zone than those with multi-lobulated pooling (P < 0.001). CONCLUSIONS OCT showed that the cystoid spaces in the OPL were accompanied by photoreceptor damage beneath the cystoid spaces in DME.