伊藤 逸毅

Purpose To determine the factors significantly associated with the amplitudes and implicit times of the flicker electroretinograms (ERGs) recorded with the RETeval system by analyzing the comprehensive data obtained during a health checkup screening. Methods Flicker ERGs were recorded with the RETeval system from 373 individuals who had a normal fundus and optical coherence tomography images. The sex, age, anthropometric, ophthalmologic, and hematologic data were collected from all participants who were 40- to 89- years-of-age. Univariable and multivariable linear mixed effects regression analyses were performed to identify factors that were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. Results Univariable linear mixed effects regression analysis showed significant correlations between the implicit times and the best-corrected visual acuity, the age, the axial length, the blood sugar level, and the blood urea nitrogen level. Analyses by multivariable linear mixed effects regression identified that the axial length (β = 0.28), the age (β = 0.24), and the blood sugar level (β = 0.092) were three independent factors that were significantly correlated with the implicit times of the RETeval flicker ERGs. Univariable linear mixed effects regression analysis also showed significant correlations between the amplitudes of the RETeval flicker ERGs and the age, the platelet count, and the creatinine level. Multivariable linear mixed effects regression models identified the age (β = -0.092), the platelet count (β = 0.099), and the creatinine level (β = -0.12) as three independent factors that were significantly correlated with the amplitudes of the RETeval flicker ERGs. However, the smoking habits, body mass index, and the blood pressure were not significantly correlated with either the implicit times or amplitudes of the RETeval flicker ERGs. Conclusions Our results indicate that the age and some ophthalmologic and hematologic findings but not the anthropometric findings were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. Thus, clinicians should remember these factors when analyzing the RETeval flicker ERGs.

PURPOSE: To determine the characteristics of eyes diagnosed with Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB) complicated by choroidal neovascularization (CNV). METHODS: This was a retrospective, multicenter observational case series. Fourteen genetically confirmed BVMD patients and 9 ARB patients who had been examined in 2 ophthalmological institutions in Japan were studied. The findings in a series of ophthalmic examinations including B-scan optical coherence tomography (OCT) and OCT angiography (OCTA) were reviewed. RESULTS: CNV was identified in 5 eyes (17.9%) of BVMD patients and in 2 eyes (11.1%) of ARB patients. Three of 5 eyes with BVMD were classified as being at the vitelliruptive stage and 2 eyes at the atrophic stage. The CNV in 2 BVMD eyes were diagnosed as exudative because of acute visual acuity reduction, retinal hemorrhage, and intraretinal fluid, while the CNV in 3 BVMD eyes and 2 ARB eyes were diagnosed as non-exudative. The visual acuity of the two eyes with exudative CNV did not improve despite anti-VEGF treatments. None of the eyes with non-exudative CNV had a reduction of their visual acuity for at least 4 years. All of the CNV were located within hyperreflective materials which were detected in 16 eyes (57.1%) of the BVMD eyes and in 7 eyes (38.9%) of the ARB eyes. CONCLUSIONS: CNV is a relatively common complication in BEST1-related retinopathy in Asian population as well. The prognosis of eyes with exudative CNV is not always good, and OCTA can detect CNV in eyes possessing hyperreflective materials.

PURPOSE: To examine the 16-week outcomes of switching to brolucizumab in eyes with neovascular age-related macular degeneration (nAMD) refractory to aflibercept. STUDY DESIGN: Retrospective observational study. METHODS: Data of eyes with nAMD who switched to brolucizumab because of resistance to aflibercept were collected. The best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status on optical coherence tomography were analyzed. RESULTS: A total of 48 eyes of 48 patients were reviewed. At 4 to 7 weeks after switching, BCVA changed from 0.26 ± 0.19 to 0.25 ± 0.21 (not significant; P = 0.95), but CRT significantly decreased from 298.9 ± 108.4 µm to 241.9 ± 92.5 µm (P < 0.001) and CCT from 182.6 ± 89.3 µm to 169.7 ± 82.6 µm (P < 0.001). Of the 23 eyes refractory to monthly aflibercept injections, 12 (52.2%) achieved a dry macula, and 8 (34.8%) reduced exudative changes at 1 month. At 16 weeks, 31 eyes (64.6%) achieved the treatment interval ≥ 8 weeks. Two patients (4.2%) dropped out, 7 eyes (14.6%) developed intraocular inflammation (IOI), and 8 eyes (16.7%) switched back to aflibercept because of the failure to extend the treatment interval ≥ 8 weeks. CONCLUSION: Switching to brolucizumab in eyes refractory to aflibercept conferred favorable outcomes in controlling exudative changes. However, IOI and the regulation of the treatment interval to at least 8 weeks during the maintenance phase disrupted the continuation of brolucizumab treatment.

Pachyvessels are pathologically dilated large choroidal vessels and are associated with the pathogenesis of several pachychoroid-related disorders, including central serous chorioretinopathy. We aimed to investigate the prevalence of and risk factors for pachyvessels in the Japanese population. We included 316 participants (aged ≥ 40 years) with normal right eyes. The presence of pachyvessels (vertical diameter > 300 µm, distance to the retinal pigment epithelium < 50 µm) was determined using 6 × 6 mm macular swept-source optical coherence tomography images, and associated risk factors were investigated. Subfoveal choroidal thickness was measured, and its associated risk factors investigated. The overall prevalence of pachychoroids was 9.5%. Regression analysis showed that a younger age, shorter axial length, male sex, and smoking were significantly associated with the presence of pachyvessels (p = 0.047; odds ratio [OR] 0.96 per year, p = 0.021; OR 0.61 per 1 mm, p = 0.012; OR 3.08 vs. female, and p = 0.011; OR 3.15 vs. non-smoker, respectively) and greater choroidal thickness (p < 0.001, p < 0.001, p < 0.003, and p < 0.017, respectively). The results were consistent with other research findings which showed that pachychoroid-related disorders such as central serous chorioretinopathy were associated with younger age, male sex, shorter axial length, and smoking. Smoking may be associated with choroidal circulatory disturbance in the Japanese population.

In the July 2020 issue, in incorrect reference was inadvertently switched with the correct reference. Reference 11 should read: Pinilla I, Idoipe M, Perdices L, et al. Changes in total and inner retinal thicknesses in type 1 diabetes with no retinopathy after 8 years of follow-up. Retina 2020; 40:1379–1386. The publisher would like to apologise for any inconvenience caused.

PURPOSE: To describe the intraoperative and postoperative morphological and functional outcomes after autologous neurosensory retinal flap transplantation (ART) for a high myopia-related refractory macular hole (MH). METHODS: This prospective interventional study enrolled five eyes of five patients (age range 54-84 years) with highly myopic refractory MHs who underwent ART. All cases were evaluated with intraoperative optical coherence tomography and postoperative optical coherence tomography, optical coherence tomography angiography, and microperimetry for at least 6 months postoperatively. RESULTS: Intraoperatively, the MH was covered by an ART flap with a persistent small subretinal space that was filled with the ART flap after 4 days to 6 days. Optical coherence tomography discriminated the original from the transplanted retina. The mean basal diameter of the original MH decreased from 1,504 ± 684 µm preoperatively to 1,111 ± 356 µm postoperatively. The best-corrected visual acuity improved in two cases, was stable in two cases, and deteriorated in one case. Microperimetry demonstrated no obvious postoperative changes in the fixation points and the absolute scotoma corresponding to the base of MHs with chorioretinal atrophy. In two eyes, choroidal neovascularization developed beneath the transplanted retinas. CONCLUSION: Transplanted tissue was in a fixed position by 1 week postoperatively with a decreased diameter of the original MH. Postoperative fixation points were on the original retina at the MH edge. Because choroidal neovascularization may develop, detailed monitoring is required.

Purpose: To describe three Japanese cases of retinal vasculitis that occurred following intravitreal brolucizumab injections and the systemic and local steroid treatment administered. Cases: Three patients developed intraocular inflammation (IOI) and retinal vasculitis following the first injection of brolucizumab for age-related macular degeneration. For two eyes, monthly aflibercept injections did not control exudation, and therapy was changed to brolucizumab; one eye was treatment-naïve. All three patients noticed blurry vision and floaters 11–18 days after brolucizumab injections, and the treated eyes exhibited anterior chamber cells, fine keratic precipitates, vitreous cells, and vitreous haze. Ultra-widefield color images of the fundus showed retinal hemorrhage in the peripheral retina and, in two cases vascular sheathing. Ultra-widefield fluorescein angiography (FA) showed segmental vascular leakage in all eyes and leakage from the optic disc in two eyes. Vascular filling defects were noted in the peripheral retinae of two eyes. Brolucizumab-associated retinal vasculitis was diagnosed, and treated with 30 mg/day of oral prednisolone, subtenon triamcinolone acetonide injection (20 mg/0.5 ml), and 0.1% betamethasone sodium phosphate solution. After 1 week, color fundus images and FA showed improvements in vascular sheathing, leakage from retinal vessels, and optic disc leakage, but the vascular filling defects remained. Visual acuity was restored in all three eyes 6 weeks after the onset. Conclusion: Brolucizumab-associated IOI, including retinal vasculitis and retinal occlusion, is a rare but important adverse event that can cause severe vision loss. Prompt diagnosis with FA and treatment with systemic or local steroids should be considered.

RATIONALE: Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease of unknown etiology. GPA affects multiple ocular tissues, most commonly the orbit, conjunctiva, cornea, and sclera. Retinal and choroidal manifestations are rare in GPA, but they often include choroidal neovascularization (CNV). PATIENT CONCERNS: A 36-year-old man was diagnosed with GPA. He had been taking oral steroid treatment for 8 years. He experienced disease recurrence and the dose of oral prednisolone was increased after steroid pulse therapy. Fundus examination showed small retinal pigment epithelial detachment and serous retinal detachment (SRD). Optical coherence tomography (OCT) revealed a protruded lesion inside the SRD. Fluorescein angiography (FA) showed a small, dot-shaped fluorescein leakage in the SRD, and indocyanine green fluorescein fundus angiography showed choroidal vascular hyperpermeability that was consistent with the hyperfluorescence seen with FA. We had to determine whether the protruded lesion inside the SRD was CNV secondary to the inflammation due to GPA or whether it was central serous chorioretinopathy (CSC)-like condition caused by high-dose steroid treatment. DIAGNOSES: We confirmed that the SRD was due to CSC but not CNV because the protruded lesion examined by B-scan OCT angiography (OCTA) showed no blood flow. INTERVENTIONS: We decided to reduce the dose of steroid. OUTCOMES: Since the reduction of steroids, no sign of worsening in the protruded lesions with SRD has been observed. LESSONS: We therefore propose the effectiveness of this advanced function of OCTA for the examination of blood flow signal images to detect CNV.

Purpose: To investigate the 4-year outcome of aflibercept treatment using a treat-and-extend (TAE) regimen for recurrent neovascular age-related macular degeneration (AMD). Study design: Retrospective observational study. Methods: Data of eyes with recurrent AMD previously treated with anti-vascular endothelial growth factor agents or photodynamic therapy and had started aflibercept treatment using a TAE regimen for the first time were collected. Best-corrected visual acuity (BCVA), intervals of treatments, the presence of exudation, central foveal thickness (CFT), and central choroidal thickness (CCT) were analyzed. Results: Of 47 consecutive eyes, 30 of the 47 eyes completed a 4-year follow-up. The mean BCVA (logMAR) was sustained over the 4 years (0.37 at baseline, 0.36 at 1 year, 0.36 at 2 years, 0.41 at 3 years, and 0.43 at 4 years, P = 0.21). Of the 30 eyes that completed the follow-up, BCVA of two eyes deteriorated by 0.3 logMAR or more at 4 years. At 4 years, 67% of eyes had extended treatment intervals to > 8 weeks, and 47% of eyes had extended intervals to > 12 weeks. Exudative changes in the macula, seen in all eyes at baseline, were only seen in 50% of the eyes at 4 years. The mean CFT and CCT decreased significantly at 4 years from 332 μm to 248 μm and from 218 μm to 183 μm, respectively. Conclusion: In clinical settings, aflibercept treatment using a TAE regimen may successfully maintain visual acuity for up to 4 years even in recurrent cases of AMD.

Purpose: To investigate whether previously reported seasonal variation and winter-dominant prevalence of acute massive submacular hemorrhages (SMHs) caused by age-related macular degeneration (AMD) disappeared, and those caused by retinal microaneurysms (RMAs) emerged. Method: The medical charts of 95 patients (95 eyes) with SMH caused by AMD and 76 patients (76 eyes) with SMH caused by RMAs in 2012–2019 were retrospectively reviewed. For each subject, the month of onset, the mean ambient temperature of that month were recorded. Results: The monthly numbers of cases of SMHs caused by AMD from January to December were 6, 8, 4, 9, 7, 10, 9, 11, 7, 11, 3, and 10. No significant seasonal variation in the monthly incidence was identified (Roger’s R = 1.89, p = 0.39). The monthly numbers of SMHs caused by RMAs from January to December were 3, 11, 11, 8, 7, 8, 5, 5, 2, 4, 7, and 5. There was significant seasonal variation in the monthly incidence (Roger’s R = 7.67, p = 0.02). There was no significant correlation between the monthly incidence of SMHs caused by RMAs and mean ambient temperature. Conclusion: Our previous study conducted for cases obtained in 1998–2005 showed seasonal cyclic trend in the number of SMHs caused by AMD, with the peak in winter. However, that significant seasonal variation disappeared in 2012–2019 in the present study. Common usage of OCT devices and anti-VEGF drugs might be the reason for the lack of seasonal variation in the cases of SMH caused by AMD. [Figure not available: see fulltext.]

PURPOSE: To examine the characteristics of polypoidal choroidal vasculopathy using B-scan optical coherence tomography angiography (OCTA), and determine the diagnostic criteria of polypoidal choroidal vasculopathy based on OCTA. METHODS: This retrospective case series included patients diagnosed with treatment-naïve polypoidal choroidal vasculopathy who underwent indocyanine green angiography (ICGA) and swept-source OCTA at baseline. We compared the characteristics of the polyps detected using B-scan OCTA and ICGA. Then, the diagnostic concordance of each polypoidal lesion between ICGA and OCTA was evaluated. RESULTS: Among 54 eyes of 52 patients, all 54 eyes showed flow signals indicating polyps on both ICGA and B-scan OCTA. All polyps on B-scan OCTA were detected as round/ring-like flow signals inside pigment epithelial detachments, incomplete round/ring-like flow signals overlaid with round/ring-like OCT structures inside pigment epithelial detachments, or flow signals adjacent to a pigment epithelial detachment notch. Using B-scan OCTA, 94.7% of the polypoidal lesions were detected by an independent evaluator with an overall accuracy of 92.6% for counting the polypoidal lesions per eye relative to ICGA and a Kappa value of 0.82. CONCLUSION: Polyp detection on B-scan OCTA demonstrates high accuracy and is comparable to that obtained on ICGA. B-scan OCTA could replace ICGA for the diagnosis of polypoidal choroidal vasculopathy.

Purpose: To report the clinical course and high resolution images of autosomal recessive retinitis pigmentosa (RP) associated with a variant of the RP1 gene (c.4052_4053ins328/p.Tyr1352Alafs*9; m1), a high frequency founder variant in Japanese RP patients. Study design: Retrospective case series. Methods: Nine patients from 5 unrelated Japanese families were studied. Five patients had the m1 variant homozygously, and 4 patients had the m1 variant compound heterozygously with another frameshift variant (c.4196delG/p.Cys1399Leufs*5). Ophthalmic examinations including adaptive optics (AO) fundus imaging were performed periodically. Results: The fundus photographs, fundus autofluorescence (FAF) images, and optical coherence tomographic (OCT) images indicated severe retinal degeneration in all the patients involving the macula even at a young age (20 s). The areas of surviving photoreceptors in the central macula were seen as hyper-autofluorescent regions in the FAF images and preserved outer retinal structure in the OCT images; they were identifiable in the AO fundus images in 8 eyes. The borders of the surviving photoreceptor areas were surrounded by hyporeflective clumps, presumably containing melanin, and the size of these areas decreased progressively during the 4-year follow-up period. The disappearance of the surviving photoreceptor areas was associated with complete blindness. Conclusion: Patients with RP associated with the m1 variant have a progressive and severe retinal degeneration that begins at an early age. Monitoring the surviving photoreceptor areas by AO fundus imaging can provide a more precise pathological record of retinal degeneration.

PURPOSE. To determine the relationship between the macular curvature and the causative genes of retinitis pigmentosa (RP). METHODS. We examined the medical records of the right eyes of 65 cases with RP (31 men and 34 women; average age, 47.6 years). There were 31 cases with the EYS variants, 11 cases with the USH2A variants, six cases with the RPGR variants, 13 cases with the RP1 variants, and four cases with the RP1L1 variants. The mean curvature of Bruch’s membrane was calculated within 6 mm of the fovea as the mean macular curvature index (MMCI, 1/μm). We used multiple linear regression analysis to determine the independence of the causative genes contributing to the MMCIs after adjustments for age, sex, axial length, and width of the ellipsoid zone. RESULTS. The median MMCI was -31.2 × 10-5/μm for the RPGR eyes, -16.5 × 10-5/μm for the RP1L1 eyes, -13.0 × 10-5/μm for the RP1 eyes, -9.8 × 10-5/μm for the EYS eyes, and -9.0 × 10-5/μm for the USH2A eyes. Compared with the EYS gene as the reference gene, the RPGR gene was significantly related to the MMCI values after adjusting for the other parameters (P = 5.30 × 10-6). In contrast, the effects of the other genes, USH2A, RP1, and RP1L1, were not significantly different from that of the EYS gene (P = 0.26, P = 0.49, and P = 0.92, respectively). CONCLUSIONS. The RPGR gene had a stronger effect on the steep macular curvature than the other ciliopathy-related genes.

Purpose: To study the changes in intraocular pressure (IOP) and aqueous flare in eyes with multiple evanescent white dot syndrome (MEWDS) during the disease course. Study design: Retrospective observational study. Methods: Twenty-one patients with unilateral MEWDS were retrospectively evaluated. IOP values were compared between the affected and fellow eyes 2 weeks, 1 month, and 3 months following disease onset in 17 patients, and within 7 days from disease onset in 11 patients. Aqueous flare values measured using a laser flare-cell meter in ten eyes between 1 weeks and 1 month from disease onset were compared between the affected and fellow eyes. Results: IOP values were significantly lower in the affected eyes than in the fellow eyes at both 2 weeks (P=0.002) and 1 month from disease onset (P=0.02). However, IOP values of affected eyes did not show significant differences from the fellow eyes within 7 days ((P=0.11) and 3 months of onset (P=0.30). Aqueous flare values were significantly increased in the affected eyes compared to those in the fellow eyes (P=0.010) and significantly correlated with IOP values (r=−0.67, P=0.035). Conclusion: IOP values mildly decreased in association with aqueous flare values in the acute phase in eyes with MEWDS.

Purpose: This study was performed to investigate the association between changes in retinal layer thickness and perfusion status in the extramacular areas of eyes with diabetic retinopathy. Design: Retrospective cross-sectional study. Methods: The medical records of 70 eyes from 55 patients with diabetes were reviewed. The status of retinal perfusion in extramacular areas was evaluated using swept-source optical coherence tomography angiography. Retinal layer thickness was measured in nonperfused areas (NPA) larger than 2 optic disc areas, areas of sparse capillaries (SC), and perfused areas (PA-DR) in eyes with diabetic retinopathy. Retinal layer thickness was also measured in perfused areas in eyes without diabetic retinopathy (PA-NDR), and the thicknesses were then compared. In addition, swept-source optical coherence tomography angiography images and retinal thickness maps were compared to investigate the distribution of retinal thickness changes and spatial relationships to areas of retinal perfusion. Results: The inner retinal thickness in NPA was significantly thinner than the inner retinal thicknesses in SC, PA-DR, and PA-NDR (all P < .001), and the inner retinal thickness in PA-NDR and SC was significantly thinner than that in PA-DR (P = .006 and .031, respectively). In a distribution analysis of the extramacular areas, NPA spatially overlapped with areas of severe retinal thinning in all locations. Local thickening with smooth shapes and gentle borders overlapped with areas of capillary abnormalities. Neovascularization was present at sites of local thickening with irregular shapes and unnatural clear borders. Conclusions: Changes in retinal layer thickness were associated with perfusion status, suggesting that retinal thickness maps can reflect perfusion status.

Purpose: To evaluate macular shape in normal eyes using swept-source optical coherence tomography (SS-OCT). Study design: Retrospective cross-sectional study. Methods: We retrospectively evaluated 77 normal eyes of 48 subjects. Curvature of retinal pitment epithelium (RPE) and choroid/scleral interface (CSI) was measured in vertical and horizontal SS-OCT 16-mm scanned images. After correcting the optical distortion of OCT images, curvatures of superior, central, and inferior sectors in the vertical scan, and temporal, central, and nasal sectors in the horizontal scan (each 4-mm length) were compared. Factors associated with overall RPE and CSI curvatures were investigated. Results: RPE and CSI curvatures of superior, central, and inferior sectors in the vertical scan were 16.6±3.1, 13.8±2.1, 17.7±3.2 and 17.8±3.0, 13.8±3.3, 18.4±3.3 (×10−5 μm−1), respectively. Central curvature was significantly flatter than superior and inferior curvatures in both RPE and CSI (all P<0.001). The RPE and CSI curvatures of temporal, central, and nasal sectors in the horizontal scan were 17.2±2.3, 15.2±2.5, 18.8±2.7 and 18.3±2.7, 16.7±2.9,14.4±2.9 (×10−5 μm−1), respectively. While central curvature was significantly flatter than nasal and temporal curvatures in RPE (P<0.001 and P=0.025), nasal curvature was significantly flatter than central and temporal curvatures (P=0.027 and P<0.001) in CSI. Overall CSI curvature was significantly associated with axial length (AL) (P<0.001), whereas overall RPE curvature was significantly associated with overall CSI curvature (P<0.001), choroidal thickness (P<0.001), and AL (P=0.038) Conclusions: This study revealed that RPE curvature is associated with CSI curvature, choroidal thickness, and AL, suggesting that choroidal and scleral structures affect macular RPE curvature.

Background: Previously, we showed that serum malondialdehyde (MDA) was significantly higher in patients with neovascular age-related macular degeneration (nAMD) than in those without AMD. The Diacron reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) tests are known markers of oxidative stress. The aim of this study was to use d-ROMs and BAP tests to evaluate changes in systemic oxidative stress in patients with nAMD. Methods: Blood serum samples were collected from 34 patients with nAMD (mean age: 76.5 ± 7.7 years; 22 men) and 20 control subjects (mean age: 62.9 ± 14.0 years; 10 men), and d-ROMs and BAP tests were examined. Results: In men, the mean level of d-ROMs for the nAMD patients was significantly higher than that for the controls (312.0 ± 52.4 vs. 275.1 ± 45.5 U.CARR, respectively; P <.05). There was a significant correlation between d-ROM level and CNV lesion area in the male nAMD group (r =.42, P =.05). There were no significant differences in mean BAP test results between the nAMD patients and controls for either sex (men: 2241 ± 549 vs. 2136 ± 246 μmol/L; women: 2263 ± 292 vs. 2335 ± 161 μmol/L). Conclusion: The d-ROMs test may provide a useful indicator of nAMD in men but not in women.

Purpose:To assess the morphological changes of cone photoreceptors in eyes with autosomal recessive bestrophinopathy.Methods:Both eyes of five patients with autosomal recessive bestrophinopathyunderwent spectral domain optical coherence tomography and adaptive optics fundus imaging. The cone photoreceptor densities were measured at intervals of 100 m between 500 m nasal and temporal eccentricities from the foveal center.Results:The median age of the patients was 30 years (range, 23-45 years), and the best-corrected visual acuity ranged from 20/20 to 20/80. Adaptive optics fundus images showed reduced cone photoreceptor densities corresponding to the damages of the photoreceptor layer in the spectral domain optical coherence tomography images in four patients with relatively good best-corrected visual acuity. The cone photoreceptor densities at the center of the fovea were less than one-third of the normal cone densities (range 11,600-30,400 cells/mm2). Cone photoreceptor mosaics were visible over the lesions with serous retinal detachment and retinal edema, although they were partially hyporeflective.Conclusion:There is a significant cone photoreceptor loss in the macular region of patients with autosomal recessive bestrophinopathy, although they had relatively good visual acuity. Monitoring cone photoreceptors by adaptive optics fundus imaging should provide accurate assessments of the disease status and indications for future therapeutic interventions.

Purpose: To study B-scan flow overlay and en face flow optical coherence tomography angiography (OCT-A) images of Type 3 neovascularization (NV) and to characterize a staging system for Type 3 NV based on the OCT-A findings. Methods: We retrospectively collected data on consecutive treatment-naive eyes with Type 3 NV. All eyes underwent fluorescein angiography, indocyanine green angiography, structural spectral domain OCT, and OCT-A (AngioPlex). Localization and extension of abnormal flows detected by B-scan flow overlay and en face OCT-A images were assessed. Results: Of 24 eyes of 22 patients with Type 3 NV, B-scan flow overlay images showed that 4.2% had telangiectatic flow in the deep retinal layer without outer plexiform layer disruption (Stage 1), 8.3% had downward intraretinal flow and subretinal flow without retinal pigment epithelium disruption (Stage 2), and 87.5% had downward flow and retinal pigment epithelium disruption (Stage 3). Of the Stage 3 eyes, 95.2% showed flow signal penetrating at the site of the retinal pigment epithelium disruption on the B-scan flow overlay images. Conclusion: We showed the characteristics of Type 3 NV using B-scan flow overlay and en face OCT-A images. B-scan flow overlay OCT-A images seem useful to improve the detection and accurate diagnosis of Type 3 NV.

Purpose: To investigate the longitudinal changes of the macular curvature in eyes with retinitis pigmentosa (RP) and to determine the factors associated with the changes. Methods: We reviewed the medical charts of 107 RP patients, for whom the axial length of their right eyes ranged from 21.5 to 26.0 mm and who had had been followed by spectral-domain optical coherence tomography (OCT). The OCT images at the initial and the most recent examinations were compared. The mean curvature of Bruch’s membrane within 6 mm of the central macula obtained from the OCT images was evalu-ated as the mean macular curvature index (MMCI). Changes in the MMCI and their relationships with other clinical factors, including the ellipsoid zone (EZ) width, were assessed. Results: The MMCI decreased significantly in the vertical OCT images, from –15.47 × 10−5 μm−1 to –16.36 × 10−5 μm−1 (P = 0.008) during the mean observation period of 3.4 ± 1.4 years (mean ± SD). This indicated that the macular shape became more concave. The change to a steeper shape was more prominent in eyes with less photoreceptor degeneration and for which the EZ width was preserved at >2000 μm. In three eyes, the MMCI increased markedly by >5 × 10−5 μm−1, and this was accompanied by absorption of the macular edema. Conclusions: The macular curvature in RP eyes becomes more concave in eyes with preserved EZ width. Translational Relevance: Longitudinal changes of the macular curvature in RP should be considered in future therapies, such as the implantation of the retinal prosthesis.

Purpose: The internal limiting membrane (ILM), the innermost basement membrane of the retina, is peeled occasionally during vitreous surgery. This study aimed to investigate the effect of ILM loss on the retina. Methods: We used optical coherence tomography to retrospectively evaluate retinal changes in 26 eyes (11 ILM-peeled and 15 ILM-unpeeled eyes) of 26 patients after vitrectomy for retinal detachment. In addition, we studied six eyes of three patients with Alport syndrome, in which ILM is genetically impaired. Results: We observed significant inner retinal displacement of the foveal pit toward the optic disk with inner retinal thickening in the nasal area (fellow, 191.9 ± 24.3 μm vs. affected, 210.3 ± 31.4 μm; P = 0.048), inner retinal thinning in the temporal area (fellow, 174.3 ± 18.3 μm vs. affected, 142.2 ± 23.6 μm; P < 0.001), foveal thickening (ILMunpeeled, 217.0 ± 39.4 μm vs. ILM-peeled, 302.0 ± 86.2 μm; P = 0.006), inner retinal dimples predominantly in the temporal area, and deviation between the foveal pit and foveal bulge. Eyes with Alport syndrome exhibited similar findings. Conclusion: Internal limiting membrane loss seems to cause characteristic inner retinal changes of the macula in both congenital and acquired conditions.

PURPOSE: Based on the hypothesis that silicone oil (SO) with a higher refractive index than water induces unexpected vignetting effects during surgeries, we aimed to investigate the relationship between the volume of SO and light intensity using a surgical microscope. METHODS: Using a light-sensitive paper and model eye filled with varying volumes (0%, 50%, 62.5%, 75%, 87.5% and 100%) of SO, the light intensity of intraocular lens (IOL) with various refractive powers (0, 10 and 20 dioptres) illuminated by a surgical microscope was measured. RESULTS: Light exposure density with 1.0% coaxial and oblique light was approximately 22-fold higher than that with 0.1% coaxial and oblique light. Further, it was approximately 34-fold higher in eyes with +20 D IOL than in those with no IOL. The density in eyes with 75% SO was the highest among all groups followed by that with 0% SO. Light exposure densities in the eyes with 75% and 0% SO were significantly higher than those with other volumes of SO. In SO-filled eyes, a microscope set with only an oblique light and a filter successfully reduced light exposure. CONCLUSION: Silicone oil-related vision loss (SORVL) during SO removal surgeries might be due to increased light exposure on the macular retina caused by the SO-associated vignetting effect. SORVL could be prevented by placing a filter in the microscope during SO removal surgeries.

Purpose: A posterior staphyloma has been reported to be present in some eyes with retinitis pigmentosa (RP), and the purpose of this study was to determine the macular curvature of non-highly myopic RP eyes. Methods: This was a retrospective, observational study. The medical charts of the right eyes of 143 patients with RP and 60 controls whose axial length ranged from 21.5 mm to 26.0 mm were reviewed. The mean curvature of Bruch's membrane within 6 mm of the central macula obtained from the horizontal optical coherence tomographic images were evaluated as the mean macular curvature index (MMCI). The relationships between the MMCI and other clinical factors were assessed. Results: The mean MMCI of RP patients (-13.73 ± 9.63 × 10-5 μm-1) was significantly lower than that of the controls (-6.63 ± 5.63 × 10-5 μm-1). This indicated a deeper concave shape of the macula in RP eyes (P < 0.001). The MMCI was significantly correlated with the age (r = 0.20; P = 0.016) and the axial length (r = -0.24; P = 0.004). Further analysis suggested a nonlinear effect of the ellipsoid zone width on the macular curvature in the RP eyes. Conclusions: There is a high incidence of steeper macular curvatures even in non-highly myopic RP eyes, and the steepness was also affected by the degree of photoreceptor degeneration.

PURPOSE: To report the findings in 3 cases of bilateral negative electroretinograms (ERGs) with acute onset of photophobia. STUDY DESIGN: Retrospective case series. METHODS: The medical charts of the 3 patients were reviewed. RESULTS: A 43-year-old woman, a 68-year-old woman, and a 41-year-old woman were referred to Nagoya University Hospital. Their main symptom was bilateral acute photophobia. None of the patients had any systemic diseases or specific medical history. The decimal best-corrected visual acuity (> 0.8) and Humphrey visual fields (mean deviation > -3 dB) were relatively well preserved in all 3 patients. The optical coherence tomography (OCT) and fundus autofluorescence findings were essentially normal. Fluorescein angiography showed mild leakage in 1 patient but no abnormality in the other 2 patients. However, the ERGs of the 3 patients had the features of abnormal ERGs found in patients with incomplete congenital stationary night blindness (CSNB). Exome analyses found no pathogenic variants related to known CSNB-related genes. The symptoms and ERGs of the 3 patients have not progressed or recovered after a relatively long follow-up period. CONCLUSION: The ERG characteristics of 3 patients with bilateral photophobia were similar to those of incomplete CSNB, suggesting post-phototransductional abnormalities. The symptoms and genetic analyses indicated the possibility of an acquired condition rather than a hereditary retinal disease.

PURPOSE: To examine the characteristics of the foveal vascular structure of patients with retinopathy of prematurity (ROP) by optical coherence tomography angiography. METHODS: Ten patients with a history of laser photocoagulation or cryopexy treatment for Stage 3 (Zone ≥ II) ROP and 10 normal subjects (controls) were included. Foveal avascular zone, vessel density, vessel length, and vascular diameter index were measured by optical coherence tomography angiography using the 3 × 3-mm Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. RESULTS: The median foveal avascular zone values of the patients with ROP and controls were 0.103 mm and 0.260 mm, respectively (P = 0.0025). The medians of the vessel density, vessel length, and vascular diameter index of the patients with ROP were 0.218 mm/mm, 11.75 mm/mm, and 18.00 μm, respectively, in ETDRS Sector 1 and did not significantly differ from those of the controls (P = 0.940, 0.733, and 0.705, respectively). For the average of ETDRS Sectors 2 to 5, the medians of the vessel density, vessel length, and vascular diameter index for the patients with ROP were 0.347 mm/mm, 18.95 mm/mm, and 18.28 μm, respectively; vessel density and vessel length were significantly smaller than those of the controls (P = 0.002 and 0.003, respectively), but there was no significant difference in vascular diameter index (P = 0.286). CONCLUSION: Optical coherence tomography angiography-guided foveal avascular zone was significantly smaller in patients with ROP than in controls. Our results indicate that foveal vascular development may be altered in patients with a history of treatment-requiring ROP.

Purpose: Subsilicone oil fluid (SOF) in eyes with silicone oil (SO) endotamponade possibly has a role in complications (e.g., vision loss); thus, we aimed to examine inflammatory cytokine and electrolyte levels and retinal glial cell viability in SOF. Methods: We measured major inflammatory cytokine levels and electrolytes in SOF and compared them with those in vitreous fluid (VF) and anterior chamber fluid (ACF). We analyzed the correlation between inflammatory cytokines and retinal thickness in SO-filled eyes. Further, we measured the MIO-M1 cell viability in medium with SOF and compared it with that containing VF. Results: We collected and examined 57 SOF, 22 ACF, and 21 VF samples from eyes with PVR, PDR, RD, and MH. Interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 levels in SOF were significantly higher than those in ACF. There was no significant difference for all cytokines between SOF and VF. Retinal thickness changes during SO endotamponade were not correlated with the presence of any inflammatory cytokines. Levels of ferrous iron, but not of potassium, showed a significant decrease in SOF compared with VF. The WST-1 assay showed that SOF-added medium induced higher MIO-M1 cell viability than VF-added medium. Conclusions: We found no significant correlation between the change in the retinal thickness and cytokine levels, but SOF contains higher concentrations of cytokines and lower concentrations of ferrous iron and can be biologically distinguished from ACF and VF. Translational Relevance: Novel knowledge of inflammatory cytokine levels and electrolytes in SOF provides better understanding of pathology of SO-filled eyes.

Rationale: Earlier studies have shown that laser photocoagulation treatments are associated with good long-term visual acuity in most patients with severe nonproliferative diabetic retinopathy (S-NPDR). Histopathologic studies of autopsied eyes have demonstrated defects in the choriocapillaris beneath the retinal laser lesions secondary to photocoagulation for S-NPDR. These lesions have been observed to expand centrifugally over time especially in the posterior pole, and the atrophy of the retinal pigment epithelium (RPE) can be significantly enlarged. There are, however, limited studies detailing the in vivo changes that occur in the RPE and choriocapillaris following laser photocoagulation. Patient concerns: A 46-year-old woman presented with visual disturbances in both eyes. Diagnoses: Fundus examinations showed many retinal hemorrhages and soft exudates in the four quadrants due to S-NPDR. Interventions: Laser photocoagulations with a 532-nm wavelength argon laser with power of 170 to 230 mW and spot size of 200 mm were performed to treat the S-NPDR. The changes in the choriocapillaris and retinal vasculature were followed by optical coherence tomography (OCT) angiography. Outcomes: The choriocapillaris beneath the laser spots was disrupted from 1 hour following the photocoagulation but it was restored at week 2. The choriocapillaris appeared almost normal at some laser spots, but they were still some spots that were altered at 1 year. The outer retina and RPE were disrupted beneath the laser spots at 1 year. On the contrary, there were no visible retinal vascular changes in the superficial and deep plexuses of retinal vasculature determined by OCT angiography with manual and automated segmentation. Lessons: The choriocapillaris in human eyes can recover after laser photocoagulation although the outer retina and RPE remain disrupted and do not recover.

The traditional classification of hypertensive retinopathy was based on the Keith-Wagener-Barker (KWB) grading, which is a subjective scaling system, and it is difficult to distinguish between the first and second grades. Retinal and choroidal vasculatures are affected by systemic hypertension, although retinal vasculature changes with age, axial length, intraocular pressure, and retinal diseases. It is necessary to establish a new objective method to assess hypertensive vascular changes. In the present study, we have examined the vasculature of the macular choriocapillaris in order to establish a new objective method to assess hypertensive vascular changes using optical coherence tomography angiography (OCTA). Choriocapillaris vessel density (VD), vessel length, and vessel diameter index in a 3 × 3 mm macular area were measured by OTCA in a total of 567 volunteers (361 healthy subjects and 206 subjects with systemic hypertension) who attended a basic health check-up. Ocular factors, systemic factors, and medications were evaluated. We detected significant differences in normative choriocapillaris vasculature between the left and right eyes in 53 healthy subjects and revealed correlations between age, intraocular pressure, axial length, and choriocapillaris vasculature in 308 healthy subjects. Normative foveal VD was correlated with age only and the efficiency was weak. The analysis of 206 right eyes (KWB grade 0, 159 eyes; grade 1, 35 eyes; and grade 2, 12 eyes) revealed that foveal VD was strongly correlated with KWB grade only (P < 0.001). This is the first report suggesting that OCTA for foveal choriocapillaris measurement by OCTA would might provide the advantage of evaluating be objective method for evaluating the progression of systemic hypertension.

Purpose: To determine the prognosis of eyes with central retinal vein occlusion that had a preserved foveal depression at the baseline and were treated by intravitreal ranibizumab injections (IRIs). Methods: The authors reviewed the medical records of 23 eyes of 23 consecutive treatment-naive patients who received IRIs to treat the macular edema due to central retinal vein occlusion. Eyes were classified by the pre-IRI presence or absence of a foveal depression. A foveal depression was defined as a central foveal thickness that was <50 m thinner than the average thickness at 200 m temporal and nasal to the central fovea. The characteristics of the two groups were compared. Results: Seven of 23 eyes had a preserved foveal depression before the IRI. The mean number of injections within 12 months after the initial IRI was significantly fewer (P < 0.001) in eyes with foveal depression (1.6 ± 0.5) than in eyes without foveal depression (4.3 ± 1.3). The mean best-corrected visual acuity at 12 months after the initial IRI was significantly better (P = 0.003) in eyes with foveal depression (0.10 ± 0.17 logarithm of the minimum angle of resolution [logMAR] units; 20/25 Snellen units) than in eyes without foveal depression (0.77 ± 0.54 logMAR units; 20/118 Snellen units). Conclusion: These results indicate that the prognosis is better for eyes with a foveal depression before the IRI treatment for a macular edema secondary to central retinal vein occlusion.

Purpose: To determine whether the macula is displaced after vitrectomy with internal limiting membrane (ILM) peeling in eyes with an idiopathic macular hole. Design: A retrospective, observational case series. Methods: Optical coherence tomography angiography was used to obtain 3 mm × 3 mm en face images before and 2, 4, and 8 weeks after the vitrectomy with ILM peeling for 20 eyes of 20 patients with an idiopathic macular hole. The displacements of easily identifiable retinal vessel bifurcations were measured relative to the fovea and the optic disc. Results: The distance between the optic disc and vessel bifurcations was significantly shorter in all 4 quadrants throughout the postoperative period (P <.001). This distance was significantly greater in the temporal quadrant (P <.001). The distance of the bifurcations was significantly correlated with the preoperative distance from the optic disc (r = −0.579, P <.001). A significantly greater downward displacement was observed in the superior quadrant (P <.001). The change in the angle of bifurcations was significantly correlated with the preoperative angle to the optic disc (r = −0.632, P <.001). The change in the distance in the inner region was significantly greater than that in the outer region in all quadrants. A significant reduction was observed in the mean foveal avascular zone area during the follow-up period. Conclusions: The retina in the macular region was displaced nasally, probably owing to movement of the retina toward the optic disc because of a contraction after the ILM removal. There is also a possibility of a rotation downward by buoyancy from gas tamponade, and centripetal contraction during the process of hole closure.

BACKGROUND: Biallelic variants of POC1B were recently reported to cause autosomal recessive non-syndromic cone dystrophy. However, the number of studies supporting this is limited, and the clinical phenotypes of cone dystrophy have not been definitively determined. The purpose of this study was to report the phenotype of a case of POC1B-associated cone dystrophy. MATERIALS AND METHODS: The medical chart of one case diagnosed with cone dystrophy was reviewed. RESULTS: The patient was a 20-year-old Japanese man whose chief complaint was a progressive decrease in his central vision. His decimal best-corrected visual acuity was 0.2 for the right and 0.3 for the left. Fundus examinations showed no abnormalities. The photopic electroretinograms were nonrecordable, but the scotopic electroretinograms were within normal limits. Optical coherence tomography detected a blurry line in the region of the external limiting membrane and ellipsoid zone. Adaptive optics images showed sparsely distributed cone cells around the fovea. The patient was initially diagnosed with incomplete achromatopsia. Whole-exome sequence with targeted analysis identified new compound heterozygous mutations of c.G1355A (p R452Q) and c.C987A (pY329X) in the POC1B gene. The patient was then diagnosed with cone dystrophy. CONCLUSIONS: The cone dystrophy associated with POC1B variants has features similar to achromatopsia, and genetic analyses is useful in discriminating these two diseases.

PURPOSE. To evaluate the microvascular changes in eyes with RP quantitatively using optical coherence tomography angiography (OCTA) and to determine whether the correlations between these indices and the severity of RP are significant. METHODS. This was a retrospective, observational study. The medical records of 53 RP patients and 46 controls were reviewed. The OCTA images were obtained with the Cirrus 5000 with Angioplex, and an automated program was used to analyze the microvascular patterns. The perfusion density (PD) and vessel length density (VLD) were used as indices of the microvascular density, whereas the vessel diameter index (VDI) was used as a measure of the caliber of the vessels. The width of the ellipsoid zone (EZ) in the OCT images and the mean deviation (MD) of the Humphry Field Analyzer (HFA) were used to determine the severity of the RP. Student’s t-tests and Spearman’s correlation tests were used. RESULTS. Both the PD and VLD in the superficial and deep plexuses and the whole retina were significantly reduced, and the VDI was significantly increased in RP patients compared with the corresponding values of the controls (P &lt 0.001). Spearman’s rank tests indicated the RP severity was significantly correlated with the PD and VLD in all three layers (P &lt 0.001, r ranging from 0.50 to 0.87) and significantly correlated with VDI in the deep and the whole retina (P &lt 0.001, ranging from −0.64 to −0.73). CONCLUSIONS. Quantitative changes in the microvascular density might be useful for examining the pathophysiology of RP.

Background: The aim of this study was to examine the change in retinal thickness after vitrectomy with internal limiting membrane (ILM) peeling and/or silicone oil (SO) endotamponade in proliferative diabetic retinopathy (PDR). Methods: The actual amount and ratio of changes in the retinal thickness were calculated. Results: Compared to control eyes in the ILM peeling (-)/SO (-) group, the central, superior inner, and temporal inner retina in the ILM peeling (+)/SO (-) group, the central and superior inner retina in the ILM peeling (-)/SO (+) group, and the central, inferior inner, temporal inner, and nasal inner retina in the ILM peeling (+)/SO (+) group showed a significant reduction of the retinal thickness. The central, superior inner, and temporal inner retina in the ILM peeling (+)/SO (-) group, the central and superior inner retina in the ILM peeling (-)/SO (+) group, and the central, superior inner, inferior inner, and temporal inner retina in the ILM peeling (+)/SO (+) group showed a significantly increased reduction rate of the retinal thickness compared to the control group. Conclusions: Macular retinal thinning in PDR was observed after ILM peeling and SO endotamponade, and it was increased by the combination of these 2 factors.

Silicone oil (SO) is an intraocular surgical adjuvant that reduces the surgical complications in refractory retinal diseases, although membrane and cellular proliferation is often seen even in SO-filled eyes. We hypothesised that the fluid in the space between the SO and the retina, named the "sub-silicone oil fluid (SOF)", enhances these biological responses. We proposed a safe method for SOF extraction. We also analysed inflammatory cytokine expressions and SOF osmotic pressures from eyes with rhegmatogenous retinal detachment (RRD), proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular hole-associated retinal detachment (MHRD). Interleukin (IL)-10, IL-12p40, IL-6, monocyte chemotactic protein-1, and vascular endothelial growth factor (VEGF) in the SOF with PVR were significantly higher than in those with RRD or MHRD. Fibroblast growth factor-2, IL-10, IL-12p40, IL-8, VEGF, and transforming growth factor beta 1 levels in eyes with exacerbated PDR indicated a significantly higher expression than those with simple PDR. IL-6 and tumour necrosis factor alpha in eyes with exacerbated PVR demonstrated a significantly higher expression than in those with simple PVR. However, there was no difference in SOF osmotic pressure between group of each disease. These studies indicate that disease-specific SOF is a significant reflection of disease status.

Purpose To investigate the regeneration of the cone outer segments in eyes after surgery for fovea-off rhegmatogenous retinal detachment with an adaptive optics (AO) fundus camera and to correlate these findings with the findings of optical coherence tomography (OCT). Design Retrospective, observational case series. Methods Medical charts of 21 eyes of 21 patients who had undergone surgery for fovea-off rhegmatogenous retinal detachment were retrospectively studied. Cone mosaic images were obtained with an AO fundus camera. Cone packing density at 2 degrees from the fovea within the previously detached area was measured 6 and 12 months after surgery. Retinal thicknesses between the interdigitation zone and the retinal pigment epithelium (IZ-RPE) and between the ellipsoid zone and the retinal pigment epithelium (EZ-RPE) were measured in OCT images. Results Cone density 12 months after surgery was significantly increased from that at 6 months (P = .001), but was still significantly lower than that of normal fellow eyes (P <.001). IZ-RPE and EZ-RPE thickness significantly increased from 6 to 12 months (P =.045, P =.033, respectively), and these values were not significantly different from those of normal fellow eyes. Multivariate analysis showed that cone density at 12 months was significantly associated with IZ-RPE thickness (P =.002), and increases in cone packing density were significantly associated with increases in IZ-RPE thickness (P =.001). Conclusions Recovery of cone packing density measured by AO was associated with structural recovery of the outer retina observed in OCT, suggesting regeneration of the photoreceptor outer segment after surgery.

PURPOSE: Patients with complete achromatopsia (ACHM) lack cone function, and patients with incomplete ACHM have relatively good visual acuity with residual color vision. The pathological mechanism(s) underlying incomplete ACHM has not been determined. The purpose of this study was to determine the pathophysiology of ACHM in two siblings: one with complete ACHM and the other with incomplete ACHM. METHODS: The medical charts of the two siblings were reviewed. RESULTS: The sibling with incomplete ACHM had decimal visual acuities that ranged from 0.4 to 0.6 and had moderate color blindness in both eyes. Her younger brother was diagnosed with complete ACHM and was not able to hold fixation, had severe pendular nystagmus, visual acuity that ranged from 0.08 to 0.1, and severe color vision abnormalities in both eyes. Optical coherence tomography (OCT) showed that the ellipsoid zone (EZ) was disruptive in the macular region in both patients. However, careful examination of the OCT images in the incomplete ACHM patient showed a high-density EZ in the central fovea. Adaptive optics (AO) fundus imaging of the sibling with incomplete ACHM revealed sparse cone mosaics remaining within 1° of the foveal center with no mosaics visible outside the central fovea. AO fundus imaging could not be performed in Case 2 because of the severe nystagmus. CONCLUSION: Our results showed that cone mosaics were present in the central fovea in the sibling with incomplete ACHM patient. This may explain the better visual acuity and color vision in this sibling.

To compare short-term outcomes of intravitreal aflibercept injection (IAI) with or without initial photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV) using focal macular electroretinography (FMERG). Observation case series. Twelve patients (6 males, 6 females; 12 eyes) with na &lt; ve PCV received 3 initial IAIs and a single session of PDT 3 days after the first IAI (combination group), and 13 patients (7 males, 6 females; 13 eyes) with na &lt; ve PCV received 3 initial IAIs only (IAI group) were retrospectively observed. Changes in visual acuity, central retinal thickness (CRT), central choroidal thickness (CCT), and FMERG parameters (FMERGs) were compared. The combination group showed improved visual acuity after the second and third IAI (P = 0.040, 0.019, respectively); both groups showed reduced CRT after the first IAI (P &lt; 0.01, each). Only the combination group showed reduced CCT after the third IAI (P = 0.031). The FMERGs of the IAI group showed improved amplitudes of a-waves after the third IAI (P = 0.026) and of b-waves after the first and third IAI (P = 0.034, &lt; 0.01, respectively); the combination group did not show improvement. The implicit times of the a- and b-waves were not changed in either group. Combination therapy and IAI monotherapy each improved visual acuity and retinal structure to a similar degree; combination therapy reduced choroidal thickness but did not improve FMERGs in the short term.

Ocular trauma is one of the leading causes of visual impairment worldwide. Because of the popularity of cataract surgeries, aged individuals with ocular trauma commonly have a surgical wound in their eyes. The purpose of this study was to evaluate the visual outcome of cases that were coincident with intraocular lens (IOL) ejection in the eyes with ruptured open-globe ocular injuries. Consecutive patients with open-globe ocular injuries were first reviewed. Patients' characteristics, corrected distance visual acuities (CDVAs) over 3 years after the trauma, causes of injuries, traumatic wound patterns, and coexistence of retinal detachment were examined. The relationships between poor CDVA and the other factors, including the complications of crystalline lens and IOL ejection, were examined. A total of 105 eyes/patients [43 eyes with rupture, 33 with penetrating, 28 with intraocular foreign body (IOFB), and 1 with perforating injuries] were included. Rupture injuries were common in aged patients and were mostly caused by falls, whereas penetrating and IOFB injuries were common in young male patients. CDVAs of the eyes with rupture injuries were significantly worse than those of the eyes with penetrating or IOFB injuries. CDVA from more than 50% of the ruptured eyes resulted in no light perception or light perception to 20/500. CDVA of the ruptured eyes complicated by crystalline lens ejection was significantly worse than that of those complicated by IOL ejection. The wounds of the ruptured eyes complicated by IOL ejection were mainly located at the superior corneoscleral limbus, whereas those of the eyes complicated by crystalline lens ejection were located at the posterior sclera. There were significant correlations between poor CDVA and retinal detachment and crystalline lens ejection. These results proposed a new trend in the ocular injuries that commonly occur in aged patients; history of cataract surgery might affect the final visual outcome after open-globe ocular injuries.

PURPOSE: The 2 most common causative genes for achromatopsia (ACHM) are CNGA3 and CNGB3; other genes including GNAT2 account for only a small portion of ACHM cases. The cone mosaics in eyes with CNGA3 and CNGB3 variants are severely disrupted; the cone mosaics in patients with GNAT2-associated ACHM; however, have been reported to show a contiguous pattern in adaptive optics (AO) retinal images. The purpose of this study was to analyze the cone mosaic of another case of GNAT2-associated ACHM. PATIENT AND METHODS: The patient was a 17-year-old Japanese boy. Comprehensive ocular examinations including fundus photography, electroretinography (ERGs), optical coherence tomography (OCT), and whole-exome analysis were performed. The cone mosaic was recorded with a flood-illuminated AO fundus camera, and the cone density was compared with those of 10 normal control eyes. RESULTS: The patient had the typical phenotype of ACHM, and a novel homozygous variant, c.730_743del, in GNAT2 was identified. The fundus did not show any specific abnormalities, and the OCT images showed the presence of the ellipsoid zone. The AO fundus image showed a clearly defined cone mosaic around the fovea. The cone density at 500 μm from the fovea was reduced by 15-30 % as compared with those of the normal eyes. CONCLUSIONS: This is the first description of a Japanese patient with ACHM with a novel GNAT2 variant. The eyes of this patient had a preserved cone structure with loss of function.

Purpose. We had earlier reported positive hsa-miR-148a-3p expression in eyes with rhegmatogenous retinal detachment (RRD) and its involvement in the epithelial-mesenchymal transition of retinal pigment epithelium in vitro. Here we investigated the association of hsa-miR-148a-3p expression levels in the vitreous fluid of patients with RRD with severity of RRD. Methods. The hsa-miR-148a-3p expression levels in the vitreous fluid, range (degree) of retinal detachment (RD), and pixels of retinal break were measured in 27 eyes with RRD. The association of hsa-miR-148a-3p expression levels with other factors was evaluated by multiple regression analysis. Results. The hsa-miR-148a-3p expression levels, time from onset of RRD to vitrectomy, range of RD, and pixels of retinal breaks were 23.68 ± 43.00, 12.07 ± 15.36 days, 155.85 ± 86.67 degrees, and 37000 ± 67100 pixels, respectively. Five eyes with RRD had vitreous hemorrhage preoperatively. The hsa-miR-148a-3p expression levels were significantly associated with pixels of retinal breaks (β = 0.699) and the time from onset of RRD to vitrectomy (β = 0.358) but not with the range of RD or presence of vitreous hemorrhage. Conclusion. The hsa-miR-148a-3p expression levels in the vitreous fluid were significantly associated with the size of retinal break and disease duration.

Retinitis pigmentosa(RP) is a hereditary retinal disease that causes photoreceptor, outer retinal, degeneration. Although the pathogenesis is still unclear, there have been numerous reports regarding inner retinal changes in RP eyes. The aim of this study is to retrospectively evaluate the changes in the thicknesses of different retinal layers of RP eyes, and its association with aqueous flare, which is used for measuring the intensity of intraocular inflammation. A total of 125 eyes of 64 patients with RP and 13 normal eyes were studied. The thicknesses of total neural retina, nerve fiber layer(NFL), ganglion cell layer(GCL), inner plexiform layer(IPL), inner nuclear layer(INL), outer layers and foveal thickness were measured in the optical coherence tomographic images. Aqueous flare was measured with a laser flare-cell meter. The associations between those parameters, visual acuity and visual field were determined in RP eyes using multivariate analysis. The results of this study showed the significant thickening of NFL, GCL and INL, the significant thinning of outer layers and the association of them with increased aqueous flare, whereas NFL and INL thickening associated with outer retinal thinning. These results can suggest the involvement of intraocular inflammation in the pathogenesis of inner retinal thickening as a secondary change following outer retinal degeneration.

PURPOSE: We report a newly developed device to fragment thrombi in retinal vein occlusion. METHODS: The new instrument consists of a 23-gauge (G) pipe and a 37-G needle with an internal wire. A total of 40 porcine eyes were used; 20 eyes for experiments in the branch retinal vein (BRV group) and 20 eyes for experiments in the central retinal vein (CRV group). We placed 25-G 3-port trocars, and core vitrectomy was performed. Another 23-G scleral incision was performed for insertion of the needle. The needle pierced the retinal vein at a distance of three- to four- or one-disc diameters from the optic disc (BRV or CRV group, respectively), and the internal wire was advanced toward the disc. The success rates of needle piercing and cannulation of the internal wire were recorded in each group. In the CRV group, the cannulation was deemed successful when the tip reached inside the optic disc. Real-time optical coherence tomography imaging also was performed using the Zeiss Rescan 700 device in porcine eyes. Histologic examination of the retinal vessel inserted with the internal wire was performed. RESULTS: The success rates of needle piercing into the BRV and CRV were 85% and 95%, respectively. The success rates of cannulation of the internal wire into the BRV and CRV were 85% and 0%, respectively. The process of cannulation was recorded successfully with the Rescan 700. Histologic examination showed no damages to the endothelial cell layer. CONCLUSIONS: The needle and internal wire intended to be used for recanalization of BRV occlusion were successfully pierced and cannulated into the BRV. TRANSLATIONAL RELEVANCE: This newly developed device could become a treatment modality for retinal vein occlusion to fragment thrombi that present treatment methods cannot reach and remove directly.

PURPOSE: To report the clinical and genetic findings of 9 Japanese patients with autosomal recessive bestrophinopathy (ARB). DESIGN: Retrospective, multicenter observational case series. METHODS: Nine ARB patients from 7 unrelated Japanese families that were examined in 3 institutions in Japan were studied. A series of ophthalmic examinations including fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, electrooculography (EOG), electroretinography, and the results of genetic analysis were reviewed. RESULTS: Genetic analyses identified 7 pathogenic variants in BEST1 including 2 novel variants, c.478G>C (p.A160P) and c.948+1delG. Homozygous variants were found in 4 families and compound heterozygous variants were found in 3 families. Two patients were diagnosed as ARB only after the whole exome sequencing analyses. The Arden ratio of the EOG was less than 1.5 in all 7 patients tested. Vitelliform lesions typical for Best vitelliform macular dystrophy were not seen in any of the patients. Seven patients shared some of the previously described features of ARB: subretinal deposits, extensive subretinal fluid, and cystoid macular edema (CME). However, the other 2 patients with severe retinal degeneration lacked these features. Focal choroidal excavations were present bilaterally in 2 patients. One case had a marked reduction of the CME and expansion of subretinal deposits over an 8-year of follow-up period. CONCLUSIONS: Japanese ARB patients had some but not all of the previously described features. Genetic analyses are essential to diagnose ARB correctly in consequence of considerable phenotypic variations.

PURPOSE. The purpose of this study was to determine microRNA expression in vitreous and subretinal fluid (SRF) samples from patients with retinal detachment (RD). The pathological importance of the identified microRNA transcript levels was analyzed in vitro. METHODS. Vitreous fluid was collected from 10 patients with macular hole (MH), vitreomacular traction syndrome (VMTS), or foveoschisis and from 11 patients with RD. Subretinal fluid was collected from 7 patients with RD. Of these, blood serum was collected in 4 patients. MicroRNA microarray profiling was performed to identify microRNA transcripts that were present in vitreous fluid, and more redundantly detected in SRF, of patients with RD, but not detected in control eyes. Western blotting and scratch assays were performed in ARPE-19 cells and primary human RPE cell lines transfected with microRNA to elucidate the effect of identified microRNA transcripts on epithelial-mesenchymal transition (EMT). RESULTS. MicroRNA microarray profiling revealed that hsa-miR-148a-3p was the most redundantly detected transcript in SRF and vitreous fluid from patients with RD, but not those with the other diseases. Expression levels of hsa-miR-148a-3p were higher in SRF samples than in blood serum samples in 3 out of 4 patients. Following hsa-miR-148a-3p mimic transfection, ARPE-19 and human RPE cells demonstrated increased expression of α-smooth muscle actin by Western blotting and increased migration ability during scratch assays. CONCLUSIONS. The results of the present study indicate that hsa-miR-148a-3p was specifically detected in RD and promotes EMT in RPE.

To report the results of scleral buckling (SB) with or without photocoagulation (PC) and intravitreal bevacizumab (IVB) for stage 4 retinopathy of prematurity (ROP) eyes. Forty-two eyes of 28 patients with SB and/or PC or IVB were studied. Twenty-nine eyes had stage 4A and 13 eyes had stage 4B ROP. Seventeen eyes underwent SB combined with additional intraoperative or postoperative treatments (combined group). Twenty-five eyes underwent SB without additional therapy (non-combined group). The concentrations of vascular endothelial growth factor (VEGF) in the aqueous humor determined by enzyme-linked immunosorbent assay were compared between the two groups. The initial and final reattachment rates were also compared. The gestational age and birth weight were 25.0 +/- A 2.0 weeks and 786 +/- A 222 g in the combined group, and 25.5 +/- A 2.1 weeks and 899 +/- A 315 g in the non-combined group. The postmenstrual age at the time of initial surgery was 38.0 +/- A 1.9 in the combined and 44.1 +/- A 4.0 weeks in the non-combined group (P &lt; 0.001). The initial reattachment rate was 92 % in stage 4A and 75 % in stage 4B of ROP eyes in the combined group, and the rate was 93 % in stage 4A and 33 % in stage 4B of ROP eyes in the non-combined group. The mean VEGF concentration in aqueous humor was 1923 +/- A 779 pg/ml in the combined group and 985 +/- A 303 pg/ml in the non-combined group (P &lt; 0.05). Our results show that the retinal reattachment rate after combined therapy was comparable to that in the non-combined group. We conclude that combined therapy may be effective even in ROP eyes with high activity.

PURPOSE. Occult macular dystrophy (OMD) is an inherited retinal disease characterized by a progressive decrease of vision and appearance of normal fundus. To determine the pathologic features of OMD, we investigated the alternation of the photoreceptors using quantitative image analysis.METHODS. We studied 22 eyes of 11 OMD patients. Three of them had a mutation (R45W) in RP1L1. The relative intensities of the ellipsoid zone in the spectral-domain optical coherence tomography (SD-OCT) images and the density of the cone photoreceptors in the adaptive optics (AO) fundus images of the OMD patients were compared to those of normal controls.RESULTS. The relative intensities of the ellipsoid zone in the SD-OCT images of patients with OMD were significantly lower (P < 0.001) by an average of 16% compared to that of the normal controls. Normal cone mosaics were not observed in the AO images of the macula in the eyes with OMD. The mean +/- SD of cone density of the 9 OMD patients was 1970 +/- 884 cells/mm(2) at 2 degrees, 1124 +/- 483 cells/mm(2) at 38, and 1288 +/- 715 cells/mm(2) at 4 degrees nasal to the fovea. The cone densities at 2 degrees, 3 degrees, and 4 degrees nasal to the fovea of OMD were significantly lower than those of the normal controls (P < 0.001).CONCLUSIONS. A sparse array of cone photoreceptors with significantly reduced density of the macula is one of the morphologic features of OMD.

Purpose:To investigate the confocal scanning laser ophthalmoscopic images obtained with near-infrared (IR) light in eyes with acute zonal occult outer retinopathy (AZOOR).Methods:Observational case series. The medical records of 12 eyes of 10 patients with AZOOR were reviewed. Scanning laser ophthalmoscopic images obtained from the AZOOR eyes were compared with images obtained by spectral-domain optical coherence tomography, by fundus autofluorescence, and by an adaptive optics fundus camera.Results:In 8 of 12 eyes, abnormal hyporeflective areas were detected in the IR images, and the other 4 eyes did not have specific abnormalities in the IR images. The boundaries of the abnormal hyporeflective areas corresponded with the border of the irregularity of photoreceptor inner segment ellipsoid band in the spectral-domain optical coherence tomography images. The cone mosaics of the adaptive optics fundus image were disrupted in the abnormal hyporeflective area of the IR image. However, the areas of fundus autofluorescence abnormalities did not coincide with the hyporeflective areas in the IR images.Conclusion:The presence of hyporeflective areas in the IR images of patients with AZOOR suggests impairment of the photoreceptors area. The IR images would be useful to evaluate eyes with AZOOR.

Purpose: To study the changes in the outer retinal microstructures during a six month period after the onset of acute zonal occult outer retinopathy (AZOOR)-complex by spectral-domain optical coherence tomography (SD-OCT). Methods: Seventeen eyes of 17 patients with the AZOOR-complex were studied. The integrity of the external limiting membrane (ELM), ellipsoid zone (EZ; also called the inner/outer segment junction), and interdigitation zone (IDZ; also called the cone outer segment tips) were evaluated in the SD-OCT images obtained at the initial visit and at six months. The three highly reflective bands were divided into three types; continuous, discontinuous, and absent. The integrity of the outer nuclear layer (ONL) was also assessed. Results: Among the three highly reflective bands, the IDZ was most altered at the initial visit and least recovered at six months. Fifteen of 17 eyes (88%) had a recovery of at least one of the three bands at six months in the retinal area where the ONL was intact, and these areas showed an improvement of visual field. Three eyes (18%) had retinal areas where the ONL was absent at the initial visit, and there was no recovery in both the retinal structures and visual fields in these areas. Conclusions: Our results indicate that more than 85% eyes with AZOOR-complex show some recovery in the microstructures of the outer retina during a six month period if the ONL is intact. We conclude that SD-OCT is a useful method to monitor the changes of the outer retinal microstructure in eyes with the AZOOR-complex.

The purpose of this paper is to report choroidal atrophy in a patient with cancer-associated retinopathy who had autoantibodies against the transient receptor potential cation channel, subfamily M, member 1 (TRPM1). A 69-year-old man visited our clinic in July 2010 with complaints of blurred vision and night blindness in both eyes. The full-field electroretinograms were negative type, indicating ON bipolar cell dysfunction. General physical examination revealed small cell carcinoma of the lung, and Western blot of the patient's serum showed autoantibodies against TRPM1. We diagnosed this patient with cancer-associated retinopathy and retinal ON bipolar dysfunction due to anti-TRPM1 autoantibody. We followed him for more than 2 years from the initial visit and his symptoms have not changed. However, consistent with the choroidal hypopigmentation of the fundus, spectral domain optical coherence tomography showed a decrease in choroidal thickness of about one third over a 2-year follow-up period. We suggest that this case of gradually progressive choroidal atrophy was caused by the autoantibody against TRPM1 directly, because TRPM1 is expressed not only on ON bipolar cells but also on melanocytes. These findings indicate that we should be aware of choroidal thickness in patients with paraneoplastic retinopathy who have retinal ON bipolar dysfunction with the anti-TRPM1 antibody. © 2014 Ueno et al.