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Yuki Nakano, Koichiro Manabe, Rie Osaka, Yukari Takasago, Aoi Ono, Mamoru Kobayashi, Tomoyoshi Fujita, Chieko Shiragami, Kazuyuki Hirooka, Akitaka Tsujikawa Department of Ophthalmology, Kagawa University Faculty of Medicine, Miki, Japan Purpose: To evaluate the effects of vitreomacular and cataract surgery on retinal oximetry in vitreomacular disease.Patients and methods: Thirty-eight eyes with epiretinal membrane (ERM) and 15 with idiopathic macular hole (MH) underwent 25 gauge pars plana vitrectomy combined with cataract surgery and intraocular lens implantation. Retinal oximetry was performed using the Oxymap T1 before, 1 month, and 6 months after surgery. Oxymap T1 simultaneously captures monochrome images of the fundus at two different wavelengths of light. Built-in Oxymap Analyzer software measures the oxygen saturation and vessel diameter.Results: Mean arterial oxygen saturation significantly increased from 96.8%±6.2% to 100.2%± 5.8% at 1 month and to 99.6%±5.8% at 6 months after surgery (P

Purpose: To compare anti-vascular endothelial growth factor (anti-VEGF) monotherapy with anti-VEGF therapy combined with sub-Tenon's capsule injections of triamcinolone acetonide (STTA) in patients with macular edema (ME) associated with branch retinal vein occlusion (BRVO)., Study Design: Retrospective observational study METHODS: This study included 186 eyes: 138 eyes received intravitreal injection of ranibizumab (IVR), and the remaining 48 eyes received IVR combined with STTA therapy. If additional IVR were necessary, STTA were performed simultaneously., Results: Both groups showed a rapid reduction in ME. The changes in logMAR visual acuity (VA) from baseline to 12 months were - 0.26 ± 0.26 in the IVR and - 0.20 ± 0.26 in the IVR with STTA groups (P = 0.209). The changes in mean central foveal thickness from baseline to 12 months were - 226.9 ± 208.2 µm in the IVR and - 236.0 ± 214.0 µm in the IVR with STTA groups (P = 0.798). The required number of IVR was 3.4 ± 1.9 in the IVR group, and 3.4 ± 1.6 in the IVR and STTA group (P = 0.950). There were no significant differences in any parameters between the two groups., Conclusion: There were no clear differences between combination therapy of anti-VEGF with STTA and anti-VEGF monotherapy for the treatment of patients with ME associated with BRVO. The number of anti-VEGF injections in patients who received the combination therapy was not reduced as compared with the number of anti-VEGF injections in patients who received the monotherapy.

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., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2019.)

Purpose: To evaluate the effect of ranibizumab on retinal oximetry in eyes with diabetic macular oedema (DME)., Methods: In this prospective interventional study, 30 eyes (30 patients) with DME were treated with three-monthly intravitreal ranibizumab injections, followed by pro re nata administration for 12 months. Retinal oximetry was performed using an Oxymap T1., Results: The mean number of injections was 6.6 ± 2.5. No adverse event was observed throughout the study period. Ranibizumab treatments for 12 months improved the macular oedema (p = 0.002) and achieved a recovery of visual acuity (VA; p = 0.011). However, oxygen saturation levels in the major retinal blood vessels, either the arteries or the veins, remained unchanged during the observational period. Arterial oxygen saturation was 100.3 ± 9.4% before treatment and 100.9 ± 10.7% (p = 0.698) at 6 months. Venous oxygen saturation was 56.4 ± 8.9% before treatment and 55.6 ± 8.6% (p = 0.529) at 6 months. In addition, there were no significant changes in diameters of the major retinal arteries and veins. Greater improvement of VA at 12 months was correlated with a smaller number of ranibizumab injections (r = 0.459, p = 0.011). The number of ranibizumab injections during these 12 months correlated with an increased baseline central retinal thickness (r = 0.385, p = 0.035)., Conclusion: Ranibizumab treatments for DME improved the macular oedema and achieved VA recovery, but no changes were noted in the retinal oxygen saturation., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To measure retinal oxygen saturation (SO 2 ) in eyes with branch retinal vein occlusion (BRVO)., Methods: Retinal oximetry was performed using the Oxymap T1 retinal oximeter in 50 eyes (50 patients) with resolved BRVO. SO 2 was calculated in each major retinal artery and vein in four quadrants. The superior or inferior hemisphere with BRVO was categorized as the affected hemisphere and the other as the unaffected hemisphere., Results: Oxymap T1 allowed us to measure SO 2 in major retinal vessels. Both arterial and venous SO 2 in the affected hemisphere were significantly higher than those in the unaffected hemisphere. However, there was no significant difference in arteriovenous (A-V) difference in SO 2 between the affected and unaffected hemispheres. Of the 50 included eyes, 32 had non-ischemic BRVO and 18 had ischemic BRVO. In the affected hemisphere, arterial SO 2 was significantly higher in ischemic BRVO (106.9 ± 8.8%) than in non-ischemic BRVO (101.3 ± 9.2%, p = 0.044). There were no significant differences in venous SO 2 between non-ischemic and ischemic BRVO. Consequently, the A-V difference in SO 2 was significantly higher in ischemic BRVO (51.9 ± 13.9%) than in non-ischemic BRVO (43.4 ± 11.5%, p = 0.028). In multiple regression analysis, the type of perfusion (non-ischemic or ischemic) had associations with arterial SO 2 (β = 0.365, p = 0.013) and with A-V differences in SO 2 in the affected hemisphere (β = 0.406, p = 0.006)., Conclusion: In ischemic BRVO, arterial SO 2 and the A-V difference in SO 2 in the affected hemisphere were significantly higher than in non-ischemic BRVO., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To compare the areas of choriocapillaris (CC) nonperfusion and macular atrophy (MA) in treated exudative age-related macular degeneration., Methods: This was a prospective, observational, cross-sectional study. Forty-four eyes exhibiting MA (42 patients with age-related macular degeneration), with a dry macula, underwent fundus autofluorescence and optical coherence tomography angiography. The area of MA detected by fundus autofluorescence and CC nonperfusion detected by optical coherence tomography angiography was measured using image analysis software. The rates of concordance between the MA and CC nonperfusion areas were calculated. We qualitatively and quantitatively compared the areas of MA and CC nonperfusion in age-related macular degeneration eyes., Results: The mean areas of MA and CC nonperfusion were 5.95 ± 4.50 mm and 10.66 ± 7.05 mm, respectively (paired t-test, P < 0.001). In 39 eyes (88.6%), the CC nonperfusion area was larger than the MA area, and the mean CC nonperfusion area was significantly larger than the mean MA area. Fundus autofluorescence matching optical coherence tomography angiography showed that the CC nonperfusion area was almost included in the MA area. The mean concordance rate for the MA area inside the CC nonperfusion area was 87.7 ± 13.9%., Conclusion: The MA and CC nonperfusion areas markedly overlapped. The area of CC nonperfusion correlated with the MA area. Choroidal ischemia might be involved in the pathogenesis of MA in treated age-related macular degeneration.

Purpose: To investigate longitudinal changes in metamorphopsia associated with branch retinal vein occlusion., Methods: In this prospective observational case series, we included 32 eyes (32 patients) with branch retinal vein occlusion and acute macular edema. Eyes were treated as needed with intravitreal ranibizumab injections for 12 months. At baseline and 1, 6, and 12 months after initiating treatment, metamorphopsia was quantified using M-CHARTS. Retinal morphology was examined through optical coherence tomography., Results: Logarithm of the minimum angle of resolution visual acuity progressively improved from 0.342 ± 0.304 (Snellen equivalent: 20/44) at baseline to 0.199 ± 0.259 (20/32) and 0.118 ± 0.195 (20/26) at 1 and 12 months, respectively (both P < 0.001). The M-CHARTS score significantly decreased from 0.63 ± 0.61 at baseline to 0.45 ± 0.50 at 1 month (P = 0.044), but no further improvement was achieved with 1 year of additional treatment (6 months: 0.47 ± 0.53 [P = 0.094] and 12 months: 0.50 ± 0.44 [P = 0.173]). Three (13.6%) of 22 eyes with baseline metamorphopsia had complete metamorphopsia resolution. At 12 months, the M-CHARTS score was correlated with baseline foveal thickness (r = 0.373, P = 0.035) and the baseline M-CHARTS score (r = 0.503, P = 0.003). A multiple regression analysis revealed that only the baseline M-CHARTS score was correlated with the 12-month M-CHARTS score (β = 0.460, P = 0.027)., Conclusions: Eyes with branch retinal vein occlusion often have persistent metamorphopsia, even when visual acuity and retinal morphology improve. Metamorphopsia at 12 months was correlated with metamorphopsia and foveal thickness at baseline., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate the type 1 choroidal neovascularization (CNV) incidence and associated factors in eyes with central serous chorioretinopathy (CSC)., Design: Retrospective case series., Methods: Records of 363 eyes (324 patients) with CSC were reviewed. Age, sex, CSC type, choroidal vascular hyperpermeability (CVH), best-corrected visual acuity (BCVA), subfoveal choroidal thickness (SCT), and systemic hypertension (HT) were assessed and compared between subjects with and without neovascular CSC., Results: We identified 219 and 144 eyes with chronic and acute CSC, respectively. The mean participant age was 55.2 ± 12.0 years, and 58 (15.6%) eyes had neovascular CSC. Age (no CNV: 54.8 ± 12.1 years, CNV: 57.3 ± 10.9 years; P = .118) and SCT (no CNV: 388.0 ± 104.5 μm, CNV: 377.4 ± 108.9 μm; P = .487) were comparable between eyes with and without CNV. However, BCVA (logarithm of the minimum angle of resolution) was significantly worse in subjects with CNV (0.28 ± 0.33 [20/38] vs 0.15 ± 0.29 [20/28]; P = .014). Neovascular CSC occurred more often in women (72 [23.6%] vs 20 [34.5%], P = .099) and in cases of chronic CSC (171 [56.1%] vs 48 [82.8%], P < .001), CVH (205 [67.2%] vs 58 [100%], P < .001), and HT (91 [29.8%] vs 24 [41.4%], P = .092). Chronic CSC (P = .001), female sex (P = .075), and poor BCVA (P = .091) were associated with neovascular CSC (multiple regression)., Conclusions: Chronic CSC, female sex, CVH, and poor BCVA are risk factors for CNV in eyes with CSC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the efficacy of periodic intravitreal aflibercept (IVA) in exudative age-related macular degeneration, and to explore the predictive factors for visual outcome.This is a prospective interventional case series.Fifty-two eyes of 52 treatment-naïve age-related-macula-degeneration patients were enrolled. All participants received IVA bimonthly following 3 monthly loading dose. The primary endpoint was change in best corrected visual acuity (BCVA) and central retinal thickness (CRT), and the secondary outcomes included changes in subfoveal choroidal thickness (SCT), macular atrophy (MA), and retinal average sensitivity (AS) determined by microperimetry at 12 months compared with baseline. The predictive factors for the change of BCVA were examined.Of 52 enrolled patients, 4 patients were drop out. Remaining 48 patients were examined. Mean logMAR BCVA significantly improved from 0.42 ± 0.37 at baseline to 0.29 ± 0.34 at 12 months (P = .008). Mean CRT and SCT significant reduced from 285.6 ± 135.2 μm, 247.9 ± 96.7 μm at baseline to 233.4 ± 98.0 μm, 208.1 ± 94.6 μm at 12 months, respectively (P < .001). At 12 months, 35 eyes of 48 eyes (72.3%) were archived dry macula. MA occurred in 7 eyes of 35 eyes with dry macula at 12 months (20.0%). AS was significant improved (P = .027) between baseline (median: 15.7 dB) and 12 months (median: 19.5 dB). The BCVA of the cases with MA involved fovea was significant worse. Age was significantly predicted for the BCVA at 12 months.IVA administered over 1 year improved BCVA, AS, and morphological findings, and the predictive factors for BCVA were age and MA-involved fovea.

Objective: The purpose of this article is to investigate the relationship between the plasma concentration of aldosterone and changes in the number of retinal ganglion cells (RGCs) after systemic administration of aldosterone., Methods: An osmotic minipump that was subcutaneously implanted into the midscapular region of rats administered 40, 80 or 160 μg/kg/day aldosterone or vehicle. Enzyme immunoassay kits were used to measure the plasma aldosterone concentrations two weeks after the systemic administration of aldosterone or vehicle. Six weeks after these systemic administrations, the number of RGCs was measured., Results: The plasma aldosterone concentrations at two weeks after systemic administration of vehicle or 160 μg/kg/day aldosterone were 238 ± 17 pg/ml and 1750 ± 151 pg/ml (748.5% ± 183.2%), respectively. There was a significant decrease in the number of RGCs in the central retina of the rats after the administration of either 80 or 160 μg/kg/day aldosterone. In the peripheral retina, however, there was a significant decrease in the number of RGCs in 40, 80 or 160 μg/kg/day aldosterone. There was a significant correlation between the number of RGCs and plasma aldosterone concentration., Conclusions: After systemic administration of aldosterone, there was a negative correlation between the plasma aldosterone concentration and the number of RGCs.

Purpose: To compare the 12-month efficacy of 1 initial intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent followed by pro re nata (PRN) dosing with that of 3 initial monthly injections followed by PRN dosing in patients with macular edema (ME) after central retinal vein occlusion (CRVO)., Methods: Twenty-nine eyes received 1 initial injection (1+PRN group) and 20 received 3 monthly injections (3+PRN group)., Results: At month 12, changes in logMAR visual acuity from baseline were -0.172 ± 0.372 and -0.142 ± 0.317 in the 1+PRN and 3+PRN groups, respectively; the difference was not significant (p = 0.769). The number of anti-VEGF injections administered in the 3+PRN group (5.9 ± 2.1) was significantly greater than that in the 1+PRN group (4.1 ± 2.8; p = 0.022)., Conclusion: When used for ME after CRVO, a 1+PRN regimen achieved 12-month outcomes similar to those of a 3+PRN regimen with fewer injections., (© 2017 S. Karger AG, Basel.)

Purpose: To evaluate the clinical features of Type 1 idiopathic macular telangiectasia (IMT) followed up for 2 years., Methods: Forty-nine patients with unilateral Type 1 IMT were examined. Thirty-one IMT eyes were treated with direct laser photocoagulation and/or intravitreal bevacizumab; the remaining 18 eyes, with good vision or slight macular edema, were untreated. Changes in best-corrected visual acuity and central retinal thickness between baseline and 24 months after the initial visit were examined., Results: Of 49 eyes, nine were treated with direct laser photocoagulation, 12 with laser photocoagulation and intravitreal bevacizumab, 10 with intravitreal bevacizumab monotherapy, whereas 18 did not receive any treatment. The mean logarithm of the minimum angle of resolution best-corrected visual acuity was 0.20 ± 0.19 (median, 20/29) and 0.13 ± 0.22 (median, 20/25) at baseline and 24 months, respectively (P = 0.023). The mean central retinal thickness was 375.0 ± 94.5 μm and 315.3 ± 78.5 μm at baseline and 24 months, respectively (P < 0.001). Retinal vein occlusion and retinal macroaneurysm occurred in six eyes and one eye, respectively, during follow-up., Conclusion: Treatment with laser photocoagulation and/or intravitreal bevacizumab may be effective for Type 1 IMT, 36.7% of IMT eyes required no treatment over a 2-year follow-up, and other retinal vascular events were not uncommon.

This prospective study aimed to investigate metamorphopsia in eyes with central retinal vein occlusion (CRVO) and included 28 eyes (28 patients) with unilateral CRVO that had macular edema (ME) in the acute phase. The ME was treated with anti-vascular endothelial growth factor agents. At baseline and at 1 and 6 months after initiation of treatment, quantitative measurements of metamorphopsia were performed using M-CHARTS and the retinal morphologic changes were examined by optical coherence tomography. At baseline, metamorphopsia was detected on M-CHARTS in 14 (50.0%) eyes. The mean M-CHARTS score was 0.37 ± 0.53. At 1 month and 6 months after initiation of treatment, there was substantial resolution of ME and significant recovery of visual acuity. In contrast, metamorphopsia was still detected in 16 eyes at 6 months; the mean M-CHARTS scores were 0.29 ± 0.37 at 1 month and 0.32 ± 0.38 at 6 months, and had not significantly improved from baseline (p = 0.580, and p = 0.604, respectively). Although the M-CHARTS score at 6 months was associated with the baseline M-CHARTS score (p = 0.004), it did not have any associations with morphologic parameters at baseline. However, the M-CHARTS score at 6 months was significantly associated with foveal photoreceptor status, height of serous detachment, and parafoveal thickening at 1 month. Metamorphopsia associated with CRVO could be quantified using M-CHARTS, and often persisted in contrast with the recovery of visual acuity and resolution of ME after treatment with anti-vascular endothelial growth factor agents.

Purpose: To investigate the parafoveal perfusion status of the superficial and deep capillary layer in eyes with resolved branch retinal vein occlusion, and to study its effects on retinal sensitivity., Methods: In 27 enrolled eyes (27 patients) with resolved branch retinal vein occlusion, superficial and deep capillaries in the macular area (3- × 3-mm, centered on the fovea) were examined with optical coherence tomography angiography. Retinal sensitivity was examined with fundus-monitored microperimetry., Results: Optical coherence tomography angiography clearly showed the parafoveal superficial and deep capillaries individually. On the affected side of retina, 25 eyes (92.6%) showed capillary nonperfusion; 23 (85.2%) in the superficial layer and 22 (81.5%) in the deep layer. Capillary nonperfusions of both layers frequently overlapped and appeared to be connected with each other. Mean (±SD) retinal sensitivity at the superficial capillary nonperfusion was 19.2 ± 6.3 dB, significantly lower than that at the superficial capillary perfusion (24.4 ± 2.8 dB, P < 0.001). Similarly, mean retinal sensitivity at the deep capillary nonperfusion was 20.8 ± 5.0 dB, significantly lower than that at deep capillary perfusion (24.3 ± 2.8 dB, P = 0.0016). Mean retinal sensitivity with superficial capillary nonperfusion was significantly lower than that with deep capillary nonperfusion (P = 0.0226)., Conclusion: Optical coherence tomography angiography visualized parafoveal capillary nonperfusion in superficial and deep layers individually in eyes with resolved branch retinal vein occlusion. Retinal sensitivity was significantly reduced at these capillary nonperfusions.

Background: Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder affecting the transport of cationic amino acid caused by mutations in solute carrier family 7 amino acid transporter light chain, y + L system, member 7 (SLC7A7). This disorder occurs worldwide, especially in Finland and Japan, where founder effect mutations have been reported. Detailed features of the clinical symptoms and mutation types in Japanese LPI, however, remain unclear to date., Methods: An epidemiological nationwide survey of LPI patients was carried out via mail to all domestic university and general hospitals in Japan. Next, the clinical information for each LPI patient was obtained, in the form of a questionnaire, from the attending physicians who replied to the letters., Results: We received answered questionnaires for 43 LPI patients in 19 hospitals. We selected 35 patients who were genetically diagnosed with LPI. The most common clinical manifestations were with protein aversion, ferritinemia, increased serum lactate dehydrogenase, and hyperammonemia. The most frequent SLC7A7 mutation in Japanese LPI patients is p.R410*, which is a founder effect mutation in northern Japan. In total, nine types of mutation were detected in this survey, six of which (p.R410*, p.S238F, c.1630delC, p.S489P, c.1673delG, and IVS3-IVS5del9.7 kb) have not been reported in other countries., Conclusion: The clinical and genetic features of 35 Japanese patients with LPI were characterized, and no correlation between genotype and phenotype was observed. The importance of early diagnosis for better prognosis of LPI is emphasized., (© 2016 Japan Pediatric Society.)