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.

INTRODUCTION: Sensory dysfunctions and cognitive impairments are related to each other. Although a relationship between tinnitus and subjective olfactory dysfunction has been reported, there have been no reports investigating the relationship between tinnitus and olfactory test results. METHODS: To investigate the relationship between tinnitus and olfactory test results, we conducted sensory tests, including hearing and visual examinations. The subjects included 510 community-dwelling individuals (295 women and 215 men) who attended a health checkup in Yakumo, Japan. The age of the subjects ranged from 40 to 91 years (mean ± standard deviation, 63.8 ± 9.9 years). The participants completed a self-reported questionnaire on subjective tinnitus, olfactory function, and hearing function, as well as their lifestyle. The health checkup included smell, hearing, vision, and blood examinations. RESULTS: After adjusting for age and sex, the presence of tinnitus was significantly associated with subjective olfactory dysfunction, poor olfactory test results, hearing deterioration, vertigo, and headache. Additionally, high serum calcium levels and a low albumin/globulin ratio were significantly associated with low physical activity and nutrition. Women scored higher than men in olfactory and hearing examinations, but there was no gender difference in vision examinations. CONCLUSION: Subjective smell dysfunction and poor smell test results were significantly associated with tinnitus complaints. Hearing and vision were associated even after adjusting for age and sex. These findings suggest that evaluating the mutual relationships among sensory organs is important when evaluating the influence of sensory dysfunctions on cognitive function.

This retrospective study aimed to evaluate choroidal hemodynamics after half-dose photodynamic therapy (PDT) for central serous chorioretinopathy (CSC) and the effects of smoking using laser speckle flowgraphy. This study included 29 eyes of 29 patients treated with half-dose PDT for CSC, who were followed-up for at least 6 months. The mean blur rate (MBR) in the PDT irradiation area (whole area), the pachyvessel (PV) area, non-PV (NPV) area, and filling delay (FD) area were assessed at baseline and 1, 3, and 6 months post-PDT, respectively. The MBR was also assessed by smoking status. The MBR significantly decreased from baseline in the whole, PV, NPV, and FD areas at all time points (P < 0.001). Of the 29 patients, 6 were never smokers, 13 were past smokers, and 10 were current smokers. At baseline, no significant difference was found in the MBR in the whole, PV, NPV, and FD areas among never, past, and current smokers. The MBR changes showed a significantly smaller decrease in current smokers than in never smokers in the whole (P = 0.021), PV (P = 0.009), and NPV (P = 0.034) areas, but not in the FD area (P = 0.172). Half-dose PDT for CSC reduced choroidal blood flow in the PDT-irradiated area, which was blunted by current smoking status.

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.

We report a case of Fabry disease diagnosed after recurrent cerebral infarction in a patient with central retinal artery occlusion (CRAO). A 23-year-old man presented with vision loss in his right eye (20/2000), showing CRAO. There was no identified cause for the loss of vision; however, corneal verticillata was detected in both eyes on the recurrence of the cerebral infarction. The α-galactosidase activity in leukocytes was significantly reduced to <0.3 nmol/mg of protein/hour, leading to a definitive diagnosis of Fabry disease. Enzyme replacement therapy was commenced concomitant to rehabilitation. It is necessary to identify Fabry disease as a cause of CRAO in young individuals, and the detection of cornea verticillata, used frequently as an ocular finding, is helpful.

PURPOSE: We report a case of neuroretinitis associated with cat scratch disease (CSD) in young children. METHOD: Case report. RESULTS: A 16-month-old boy was admitted for a detailed examination and treatment of a fever of unknown origin. Blood tests revealed no significant findings other than a white blood cell count of 16,100/mm3 and C-reactive protein level of 9.89 mg/dL. Computed tomography revealed no relevant findings to determine the causative disease. Antibiotic therapy with cefotaxime was initiated; however, the fever did not resolve. The patient was referred to our department for further examination to detect the cause of the fever. Fundoscopy revealed neuroretinitis in the right eye. His mother reported a history of breeding cats. Cat scratch disease (CSD) was suspected based on the clinical course and fundus findings. Cefotaxime was discontinued, and azithromycin, rifampicin, and prednisolone were administered, following which the fever disappeared and fundus findings improved. Immunoglobulin G (IgG) and IgM antibodies against Bartonella henselae was positive, leading to a definitive diagnosis of CSD. CONCLUSION: Infants cannot complain of decreased visual acuity; therefore, these findings may be overlooked unless a fundus examination is performed. As in this case, the early detection of neuroretinitis by an ophthalmologist may help in the diagnosis of CSD. It is extremely difficult to capture a photograph of the fundus of an infant, and recording with a smartphone is relatively simple and useful for monitoring continuous changes. Summary. We describe a case of neuroretinitis associated with cat scratch disease (CSD) that was diagnosed on the basis of fundus findings. The findings suggest the importance of an aggressive ophthalmologic examination when CSD is suspected in young children who are unable to describe their symptoms.

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 Vessel maturation is considered to proceed by pruning branches resulting in less branching vessels. This study investigated the vessel junction densities of type 1 and type 2 choroidal neovascularizations (CNVs) using optical coherence tomography angiography (OCTA). Methods We collected consecutive data from treatment-naïve eyes diagnosed with typical age-related macular degeneration (AMD). The OCTA images with CNV were analyzed to calculate vessel areas, vessel lengths, and vessel junction densities. Results Of 60 eyes in 60 patients, type 1 CNV diagnoses had been made in 40 eyes, and type 2 CNV in 20 eyes. We found no significant difference in vessel areas between type 1 CNV and type 2 CNV (type 1 CNV, 0.44 ± 0.37 mm2 type 2 CNV, 0.37 ± 0.48 mm2), and no significant difference in vessel lengths (type 1 CNV, 18.24 ± 15.96 mm type 2 CNV, 16.13 ± 21.45 mm). However, the vessel junction density of type 1 CNV was significantly lower than that of type 2 CNV by 16.0% (P = 0.008). Conclusion OCTA revealed that the vessel junction densities of type 1 CNVs were lower than those of type 2 CNVs, suggesting type 1 CNV vessels are more mature than type 2 CNV vessels.

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 assess predictive factors and surgical outcomes for myopic traction maculopathy. Methods: This retrospective observational case study enrolled 73 patients who underwent vitrectomy for myopic traction maculopathy. The 79 eyes obtained from our study sample were divided into 4 types: Retinoschisis, lamellar macular hole (lamellar MH), foveal retinal detachment (FRD), and FRD + lamellar MH, or into 2 types according to the presence of FRD preoperatively. Dependent variables of interest were age, sex, pre- and postoperative best-corrected visual acuity (BCVA) at 6 months, and axial length. Results: All the four types showed moderately strong-to-strong positive correlations with pre- and postoperative BCVA (retinochisisi: R = 0.61 lamellar MH: R = 0.62 FRD: R = 0.51 FRD + lamellar MH r = 0.83). Preoperative BCVA was associated with postoperative BCVA (P , 0.0001), but age, axial length, and the types of preoperative foveal status were not. Eyes with FRD had significantly worse pre- and postoperative BCVA than eyes without FRD (P = 0.036 and P = 0.046, respectively). Postoperative full-thickness macular holes developed in 5.1% of cases and in all types but retinoschisis. Conclusion: Preoperative visual acuity and the presence of FRD should be considered for surgical indication of myopic traction maculopathy.

Purpose: Hyperreflective foci (HRF) in the outer retina are associated with the progression of multiple retinal diseases, but their pathogenic significance in retinitis pigmentosa (RP) remains obscure. We studied outer retinal HRF number and distribution in RP using spectral-domain (SD) OCT and assessed associations with visual field loss, retinal inflammation, and photoreceptor degeneration. Design: Retrospective cross-sectional study. Participants: Medical records of 128 eyes of 66 RP patients (mean age, 45.7±16.1 years range, 10–85 years). Methods: All participants underwent high-resolution SD-OCT. Outer retinal HRF were counted on vertical and horizontal SD-OCT images centered at the fovea of 55 eyes of 29 patients. In addition, SD-OCT macular volume scans of 92 eyes of 48 patients were reviewed and compared with fundus autofluorescence images of the same area to investigate outer retinal HRF distribution and the spatial relations to areas of low autofluorescence and photoreceptor inner segment and outer segment junction (IS/OS) preservation. Main Outcome Measures: The number and distribution of outer retinal HRF, aqueous flare value, thickness of outer layers, visual field area, and fundus autofluorescence. Results: In the HRF counting analysis, the mean number of outer retinal HRF per scan was 24.0±18.6, mean aqueous flare value was 7.7±3.2 photon count/ms, visual field area was 25.2±26.6%, and thickness of the outer layers was 95.2±39.6 μm. Generalized estimating equations revealed that the number of outer retinal HRF was associated positively with aqueous flare value (P = 0.01) and associated negatively with visual field area and outer layer thickness (P = 0.016 and P &lt 0.001, respectively). In the distribution analysis, macular areas exhibiting outer retinal HRF (HRF areas) spatially overlapped with areas of low autofluorescence. In contrast, HRF areas did not overlap with areas showing preserved IS/OS. Conclusions: Outer retinal HRF number is associated with intraocular inflammation and photoreceptor degeneration in RP. Their distribution in areas with IS/OS disruption and low autofluorescence suggests that outer retinal HRF reflect defects in the retinal pigment epithelium (RPE) layer caused by RPE cell or microglial migration in response to photoreceptor degeneration.

Purpose: To investigate the microvascular changes in choroidal neovascularization (CNV) using optical coherence tomography angiography (OCTA) during anti-vascular endothelial growth factor (VEGF) therapies. Methods: We retrospectively collected data on consecutive treatment-naïve eyes with typical age-related macular degeneration that initially received 3 aflibercept injections. OCTA was performed at baseline and at 1, 2, and 4 months of follow-up. The CNV images were analyzed using open-source software to assess vessel area and junction density. Results: Fifteen eyes of 15 patients were included. The mean vessel area at baseline was 0.50 ± 0.33 mm2 at 1, 2, and 4 months, the ratios of change in vessel area from baseline were 66.6 ± 38.8%, 80.5 ± 25.5%, and 94.0 ± 29.3%, respectively. The vessel area was significantly reduced at 1 month from that at baseline (p = 0.0015) but significantly increased at 4 months from that at 1 month (p = 0.011). The mean junction density was also significantly reduced from 4.70 ± 1.30/mm at baseline to 3.82 ± 1.06/mm at 1 month (p = 0.00084). However, junction density did not continue to decrease at 2 and 4 months. Conclusion: OCTA quantification revealed that CNV rebounded after repeat aflibercept injections despite shrinking in response to the first injection.

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.

Sex-related differences are present in the systemic and ocular blood flow. However, the cause of the sex-related differences has not been determined. We investigated the ocular blood flow, represented by the mean blur rate (MBR), on the optic nerve head (ONH) determined by laser speckle flowgraphy in 138 males (63.9 ± 8.9 years) and 194 females (63.5 ± 9.4 years). The correlations between the MBR on the ONH and the clinical data were determined. The overall ONH-MBR was significantly higher in females than males (P < 0.001). In addition, the levels of the hemoglobin and hematocrit were significantly lower in females than in males (P < 0.001). The ONH-MBR was negatively and significantly correlated with the levels of the hemoglobin and hematocrit (both, P < 0.001). Multiple regression analyses showed that the sex (β = 0.248, P < 0.001) was an independent factor correlated with the ONH-MBR when the clinical examination data were not included in the analyses. However, when the clinical examination data were included, the hemoglobin level (β = -0.295, P < 0.001) was an independent factor that contributed to the ONH-MBR but the sex was not. We conclude that the sex-related differences in the hemoglobin level and the negative correlation between hemoglobin and the ONH-MBR are the causes of the sex-related differences in the ONH-MBR.

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.

Purpose: To report a novel finding in a case of idiopathic recurrent branch retinal arterial occlusions. Observations: We report our findings in a 31-year-old woman with an idiopathic recurrent branch retinal arterial occlusions (BRAOs) who was followed in our clinic for 16 years. Repeated fluorescein angiographies were performed to evaluate the idiopathic recurrent BRAOs. The findings showed multiple segmental arteriolar staining in the fundus. These staining were found at locations with and without branch retinal arterial occlusions. Repeated fluorescein angiography showed that these staining migrated toward the periphery. The speed of the migration of the staining was about 0.64 ± 0.22 mm/day with a range of 0.43–0.85 mm/day in the posterior pole of the eye. In each of the BRAO, the staining did not cause branch retinal arterial occlusions in the peripheral retina again. Conclusions and importance: Segmental arteriolar staining that migrates towards the periphery may be a clue to the etiology of this disease process.

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.

Purpose: To evaluate the relationship between morphological changes and functional improvements assessed using focal macular electroretinograms after intravitreal aflibercept (IVA) injections in eyes with wet age-related macular degeneration. Methods: The clinical records of 42 eyes of 42 consecutive patients with naive, wet agerelated macular degeneration received 3 monthly IVA were reviewed. The best-corrected visual acuity, central foveal thickness, outer retinal thickness, inner retinal thickness at baseline and 1 month after each IVA, and focal macular electroretinograms at baseline and 1 month after the first and third IVA were compared. Results: Best-corrected visual acuity was improved after the third IVA (P = 0.0091). Central foveal thickness and outer retinal thickness showed decreases after every IVA (P &lt 0.001, respectively). Inner retinal thickness showed a decrease after the second IVA (P = 0.002), after and third IVA (P = 0.001). On focal macular electroretinograms, a-and b-wave amplitudes showed increases after the third IVA (P = 0.0028, P = 0.0012, respectively). Significant correlations were observed between best-corrected visual acuity and central foveal thickness, a-wave amplitude and outer retinal thickness, and b-wave amplitude and inner retinal thickness changes after the third IVA. Conclusion: All parameters significantly recovered after three monthly IVA, with a correlation between functional improvements and morphological changes.

Purpose: To test the hypothesis that the thickness of outer retinal layers will change with increasing age in normal eyes and in the normal fellow eyes of patients with unilateral agerelated macular degeneration. Methods: Spectral domain optical coherence tomography images of 127 normal eyes of 127 subjects and 58 normal fellow eyes of 58 patients with unilateral age-related macular degeneration were studied. The thickness between the retinal pigment epithelium line and the cone outer segment tips line, between the cone outer segment tips line and the photoreceptor inner segment/outer segment line, and between the inner segment/outer segment line and the external limiting membrane line were measured at the fovea in both groups. Results: The thickness between retinal pigment epithelium line and the cone outer segment tips line, and between inner segment/outer segment line and the external limiting membrane line were significantly and negatively associated with age in the normal group. Cone outer segment tips line and the photoreceptor inner segment/outer segment thickness was not significantly associated with age. Retinal pigment epithelium line and the cone outer segment tips line was thinner in the fellow eyes of patients with unilateral age-related macular degeneration than in the age-matched normal eyes. Cone outer segment tips line and the photoreceptor inner segment/outer segment and inner segment/ outer segment line and the external limiting membrane line thicknesses in the fellow eyes were not significantly different from that of normal eyes. Conclusion: The tissue between the retinal pigment epithelium line and the cone outer segment tips line may become atrophic in older eyes and in the normal fellow eyes of patients with unilateral age-related macular degeneration.

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.