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Abstract Govetto’s staging system (stages 1–4) for epiretinal membrane (ERM) based on optical coherence tomography images is a useful predictor of monocular visual function; however, an association between Govetto’s stage and binocular vision has not been reported. This study aimed to investigate the factors associated with Govetto’s stage among the monocular and binocular parameters. This retrospective study included consecutive patients with treatment-naïve eyes with unilateral ERM without pseudo-hole. We investigated Govetto’s stage, degrees of aniseikonia and metamorphopsia, foveal avascular zone area, central retinal and choroidal thickness, vertical ocular deviation, stereopsis, and binocular single vision (BSV). We compared the parameters between the BSV-present and BSV-absent groups and investigated correlations between Govetto’s stage and the monocular and binocular parameters. Twenty-eight eyes of 28 patients were examined (age, 66.6 ± 10.2 years). In multivariate correlation analyses, Govetto’s stage correlated with BSV (P = 0.04, β = − 0.36) and central retinal thickness (P

Abstract This retrospective observational study aimed to investigate the difference in 4-year outcomes of ranibizumab or aflibercept therapy for macular neovascularization (MNV) with high myopia between pathologic myopia (PM) and non-PM. This study was conducted at Kyoto University Hospital and included consecutive treatment-naïve eyes with active myopic MNV, in which a single intravitreal ranibizumab or aflibercept injection was administered, followed by a pro re nata (PRN) regimen for 4 years. Based on the META-PM study classification, eyes were assigned to the non-PM and PM groups. This study analyzed 118 eyes of 118 patients (non-PM group, 19 eyes; PM group, 99 eyes). Baseline, 1-year, and 2-year best-corrected visual acuity (BCVA) were significantly better in the non-PM group (P = 0.02, 0.01, and 0.02, respectively); however, the 3-year and 4-year BCVA were not. The 4-year BCVA course was similar in both groups. However, the total number of injections over 4 years was significantly higher in the non-PM than in the PM group (4.6 ± 2.6 vs. 2.9 ± 2.6, P = 0.001). Four-year BCVA significantly correlated only with baseline BCVA in both non-PM (P = 0.047, β = 0.46) and PM groups (P

Purpose: To elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA). Design: Retrospective, multicenter, observational study. Participants: A total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from 6 university hospitals in Japan were included. All patients were Japanese, aged ≥50 years and with fundus autofluorescence images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group. Methods: The studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semiautomatically measured on fundus autofluorescence images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype. Main Outcome Measures: Clinical characteristics and progression rates of pachychoroid and conventional GA. Results: The pachychoroid GA group was significantly younger (70.3 vs. 78.7 years; P < 0.001), more male-dominant (89.5 vs. 55.6%; P < 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution; P = 0.002), thicker choroid (312.4 vs. 161.6 μm; P < 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%; P < 0.001), and smaller GA area (0.59 vs. 3.76 mm2; P < 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs. 0.27 mm/year; P < 0.001). Conclusions: Demographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in White populations. Some characteristics of GA in Japanese population differ from those in Waucasian populations, which may be due to the inclusion of pachychoroid GA. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract Internal limiting membrane (ILM) peeling requires a delicate handling technique. It is also important that ophthalmologists can use the ILM forceps handle of their preference. This study objectively and subjectively evaluated the handling of the novel Finesse Reflex Handle (Reflex) in comparison with that of a conventional handle. The force required to close the forceps tips, evaluated using a digital force gauge, was significantly lesser for Reflex than for the conventional handle (3.14 ± 0.09 N vs. 3.84 ± 0.06 N, P

Purpose: To evaluate the severity scales of diabetic macular ischemia (DMI) by analyzing the quantity and distribution of capillary nonperfusion using OCT angiography (OCTA) images. Design: A single-center, prospective case series. Participants: Three hundred one eyes from 301 patients with diabetic retinopathy. Methods: We acquired 3 × 3-mm swept-source OCTA images and created en face images within a central 2.5-mm circle. The circle was divided into 15 × 15-pixel squares and nonperfusion squares (NPSs) were defined as those without retinal vessels. Eyes with high-dimensional spatial data were arranged on a 2-dimensional space using the uniform manifold approximation and projection (UMAP) algorithm and classified by clustering into 5 groups: Initial, Mild, Superficial, Moderate, and Severe. Main Outcome Measures: Development of a severity scale for DMI. Results: Eyes arranged on a 2-dimensional UMAP space were divided into 5 clusters, based on the similarity of nonperfusion area distribution. Nonperfusion square counts in the deep layer increased in eyes of the Initial, Mild, Moderate, and Severe groups in a stepwise manner. In contrast, there were no significant changes in superficial NPS counts between eyes of the Initial and Mild groups. In the intermediate stage, eyes of the Superficial group exhibited higher NPS counts in the central sector of the superficial layer compared with those of the Moderate group. The foveal avascular zone extended into the temporal subfield of the deep layer in eyes of the Moderate group. Eyes of the Severe group had significantly poorer visual acuity that was more frequently accompanied with proliferative diabetic retinopathy. Conclusions: The application of dimensionality reduction and clustering has facilitated the development of a novel severity scale for DMI based on the distribution of capillary nonperfusion in OCTA images. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Wyburn-Mason syndrome is an extremely rare disorder with a limited number of reported cases. Its underlying pathology is poorly understood. This case report focuses on a 41-year-old woman presenting with visual impairments and retinal arteriovenous malformations, highlighting the critical role of multimodal imaging in diagnosing this complex condition. Through the application of fluorescein angiography, optical coherence tomography (OCT) angiography, and OCT B-scan, this study provides vital insights into the vascular anomalies associated with Wyburn-Mason syndrome. These findings enhance our understanding of the ophthalmologic features of Wyburn-Mason syndrome and highlight the importance of detailed diagnostic processes.

Purpose: We report a case of laser-induced retinopathy that posed diagnostic challenges with conventional spectral domain optical coherence tomography (SD-OCT), but was successfully diagnosed using adaptive optics-optical coherence tomography (AO-OCT). Observations: A 27-year-old man with a history of occupational laser device use presented with central scotoma and visual disturbances in the right eye. Conventional SD-OCT only revealed decreased reflectivity in parts of the foveal ellipsoidal zone band. However, other multimodal observations indicated damage to the retinal pigment epithelium (RPE) and choriocapillaris. Additionally, a well-defined circular, dark lesion, approximately 80 μm in diameter, was identified in the outer retina. AO-OCT demonstrated the absence of the RPE and Bruch's membrane, accompanied by the loss of inner and outer segments of cone photoreceptors and dropout of cone cell nuclei, with Müller cells remaining unaffected. Conclusions and Importance: This case of laser-induced retinopathy advances our understanding of the pathophysiological effect of laser exposure on the retina, suggesting a higher incidence of laser-induced retinopathy than previously diagnosed. It also serves as a crucial reminder for laser users to exercise caution and highlights the necessity for ophthalmologists to carefully observe and examine such cases.

Purpose: This case report details the diagnostic process for a patient with an initial diagnosis of scleritis who was unresponsive to typical treatment modalities, culminating in the identification of a cavernous sinus dural arteriovenous fistula (CS-DAVF). The case highlights the role of anterior segment optical coherence tomography angiography (OCTA) in the diagnosis of this vascular anomaly and in monitoring the response to treatment. Observations: A 45-year-old man with persistently elevated intraocular pressure (IOP) and ocular congestion in the left eye was unresponsive to treatment for scleritis. The persistent ocular symptoms and new-onset tinnitus prompted further investigation. Anterior segment OCTA revealed vascular anomalies, and magnetic resonance imaging confirmed a CS-DAVF. The patient underwent endovascular treatment for the CS-DAVF. This intervention led to a significant reduction in IOP in the left eye and the resolution of ocular congestion. Conclusions and importance: This case highlights the diagnostic complexities of ophthalmic symptoms that mimic those of other conditions. Furthermore, it demonstrates the essential role of anterior segment OCTA in the accurate diagnosis and effective management of CS-DAVF and highlights the need for comprehensive diagnostic approaches in ophthalmology.

Abstract This study aimed to analyze the trends and factors influencing the number of ophthalmic surgeries in Japan using the open data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan published by the Ministry of Health, Labour and Welfare. We calculated the number of cataract, glaucoma, and vitreoretinal surgeries, categorized by sex, age, and surgical type, for the fiscal years (FY) 2014 to 2020. The number of cataract surgeries remained stable at approximately 1.45 million cases from FY 2014 to 2018, increased to nearly 1.6 million cases in FY 2019, and decreased to 1.45 million cases in FY 2020. Among glaucoma surgeries, surgical treatments were increased 1.8 times over 7 years, from 33,000 to 60,000 cases. Laser treatment remained steady at around 55,000 cases from FY 2014 to 2017 and then increased to approximately 60,000 cases. The number of vitreoretinal surgeries was increased 1.2 times from FY 2014 to 2019, from 120,000 to 140,000, and decreased to 130,000 by FY 2020. Trends in ophthalmic surgeries over the past 7 years may be influenced by population aging, minimally invasive surgery, and the coronavirus disease pandemic. These findings have implications on surgical decision-making and resource allocation.

Abstract In retinitis pigmentosa (RP), photoreceptor degeneration leads to progressive visual field loss and visual impairment. Several therapeutic trials are ongoing aiming to establish effective treatments. Although functional evaluations are commonly used in clinical trials, residual ellipsoid zone (EZ) measurement on optical coherence tomography has been shown to be more sensitive to detect disease progression. Establishment of sensitive outcome measurement is essential to develop new therapeutic strategies. In the current study, we evaluated the progression rates of the disease in 76 eyes of 76 patients with RP, using the residual EZ length, ring-shaped macular hyperautofluorescent (AF), and visual field. Decrease rates measured by the residual EZ area and by the hyper-AF ring area were strongly positively correlated (P

Abstract Though vascular endothelial growth factors (VEGF) and other proangiogenic factors, such as angiopoietins (Ang), may be involved in the development of neovascular age-related macular degeneration (nvAMD), only drugs that inhibit the VEGF family are available for the treatment. The newly approved anti-VEGF drug faricimab, which also inhibits Ang-2, is expected to be effective in patients with AMD refractory to conventional anti-VEGF drugs. Therefore, we prospectively investigated the efficacy of faricimab in the treatment of aflibercept-refractory nvAMD. Patients with nvAMD who had been treated with aflibercept in the last year and required bimonthly injections were recruited. 25 eyes showed persistent exudative changes immediately before the faricimab injection (baseline). In these 25 eyes, switching to faricimab did not change visual acuity or central retinal thickness 2 months after the injection; however, 56% of eyes showed reduction or complete absorption of fluid. Notably, 25% of the eyes that showed dry macula at month 2 had no fluid recurrence for up to 4 months. These results indicate that faricimab could benefit some patients with aflibercept-refractory nvAMD.

Purpose: The aim of this study was to examine the effects of foveal thickness (FT) fluctuation (FTF) on 2-year visual and morphological outcomes of eyes with central retinal vein occlusion (CRVO) undergoing anti-VEGF treatment for recurrent macular edema (ME) based on a pro re nata regimen. Design: Retrospective, observational case series. Participants: We analyzed 141 treatment-naive patients (141 eyes) with CRVO-ME at a multicenter retinal practice. Methods: We assessed FT using OCT at each study visit. Patients were divided into groups 0, 1, 2, and 3 according to increasing FTF. Main Outcome Measures: We evaluated the logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA), the length of the foveal ellipsoid zone (EZ) band defect measured using OCT, and the association of FTF with VA and EZ band defect length. Results: The mean baseline logMAR BCVA and FT were 0.65 ± 0.52 (Snellen equivalent range: 20/20–20/2000) and 661.1 ± 257.4 μm, respectively. The mean number of anti-VEGF injections administered was 5.6 ± 3.6. At the final examination, the mean logMAR BCVA and FT values were significantly improved relative to the baseline values (both P

Purpose: We aimed to describe the epidemiology of angioid streaks (AS) and pseudoxanthoma elasticum (PXE), which are rare diseases, using a national claims database. Design: This was a population-based longitudinal cohort study. Participants: A total of 126 million individuals were covered by the universal health coverage system in Japan. Methods: With permission from the Ministry of Health, Labor and Welfare, we accessed all data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, which contains the nationwide health insurance claims data for 126 million Japanese. We identified individuals with AS and PXE between January 2011 and December 2020. The incidence rates, prevalence, overlap of AS and PXE, and mean age at death were calculated. Main Outcome Measures: The incidence rates and prevalence of AS and PXE. Results: A total of 6598 cases of AS and 1020 cases of PXE were identified during the 10-year study period. The incidence rates of AS and PXE were 0.52 (95% confidence interval, 0.48–0.56) and 0.08 (95% confidence interval, 0.07–0.10) per 100 000 person-years, respectively. On October 1, 2020, the prevalence of AS and PXE was 6.5 (95% confidence interval, 6.38–6.66) and 0.83 (95% confidence interval, 0.78–0.89) per 100 000 persons, respectively. The overlap of AS and PXE was 363 patients. The mean age at death of individuals with AS and PXE was 79.3 ± 0.51 and 77.1 ± 2.68 years, respectively. Conclusion: This is the first population-based study to elucidate the epidemiology of AS and PXE. The mean age of death of both AS and PXE patients was younger than the mean life expectancy of the general Japanese population, thus, appropriate diagnosis and management are important to avoid preventable death. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background: We report an unusual case of retinal vein occlusion (RVO) associated with vitreous hemorrhage (VH) without visible traction from the posterior vitreous membrane (PVM) at the bleeding point, challenging our current understanding of VH pathophysiology. Case presentation: A 52-year-old man presented with VH in the right eye. A detailed examination using optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography revealed branch RVO with non-perfused areas (NPAs) extending peripherally and neovascularization elsewhere (NVE). OCTA showed NVE infiltrating the vitreous cavity, leading to substantial bleeding without visible PVM traction at the bleeding point. The NVE was successfully removed following vitrectomy, and visual acuity improved from 20/20 to 20/13 preoperatively, along with a postoperative improvement in floaters. Conclusions: This unique case of RVO suggests the possibility of VH occurring independent of PVM contractions at the bleeding point, challenging the traditional understanding of VH. This finding underscores the potential role of OCTA in diagnosing and managing retinal vascular diseases, underscoring the need for further investigations into the underlying mechanisms, with potential implications for personalized therapeutic strategies.

Abstract Morphological changes in capillaries are one of major clinical signs in diabetic retinopathy (DR). In this study, we quantified the dilated deep capillaries on optical coherence tomography angiography (OCTA) images. Central 3 × 3 mm en face images were obtained using a swept source OCTA device in 105 eyes of 99 patients with DR. Capillaries with a greater diameter in the deep layers were defined as the dilated deep capillaries, using stepwise image processing. The relative areas of automatically selected capillaries with a great diameter were calculated as the index of the dilated deep capillaries. Most eyes with DR had string-like or dot-like dilated deep capillaries in the OCTA images, which appeared to be dilated capillary segments or microaneurysms histologically. They were distributed more densely in the parafovea than in the central sector, while there were no differences between individual quadrants. The index of the dilated deep capillaries was higher in eyes with DR than in nondiabetic eyes. The index in the central subfield was modestly associated with visual acuity, diabetic macular edema, and proliferative diabetic retinopathy. The quantitative dilated deep capillaries are designated as a biomarker of vision-threatening DR.

Abstract We aimed to obtain widefield (WF) swept source optical coherence tomography (SS-OCT) data and examine the features of choroidal thickness maps in healthy eyes. The posterior pole choroidal thickness was examined in 127 eyes using enhanced depth imaging of SS-OCT with a viewing angle of 20 (vertical) × 23 (horizontal) mm, and choroidal thickness maps were generated. For SS-OCT image analysis, we developed a grid with inner and outer rings, each divided into superotemporal, inferotemporal, superonasal, and inferonasal quadrants, comprising a total of nine subfields, including the central 3-mm ring. The posterior pole choroidal thicknesses were significantly lower at the periphery than in the central area, in the inferior field than in the superior field, and in the nasal field than in the temporal field (p

Abstract We examined the effect of reduced fluence (rf)-photodynamic therapy (PDT) of the macular area on the wide-field choroidal thickness in 20 eyes with central serous chorioretinopathy (CSC) and 20 age- and sex-matched control eyes. The choroidal thickness at the posterior pole was measured before and after rf-PDT, using a grid with inner and outer rings, each divided into superotemporal, inferotemporal, superonasal, and inferonasal quadrants, respectively, making up a total of nine subfields including the central 3 mm ring. Before treatment, all eyes showed wide-field choroidal thickening from the dilated vortex vein ampulla to the fovea, along the course of the vein. After rf-PDT of the macular area, the choroidal thickness significantly decreased, not only in the irradiated macular area but also outside the arcade vessels in all quadrants (p 0.05 for all subfields). These findings provide new insights into the pathogenesis of CSC and explain the reasons for the effectiveness of rf-PDT for this condition.

BackgroundEpiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries.Methods and designThis is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications.DiscussionThe results of this study will support the surgical decisions and procedures in ERM practices.

Objective: To investigate cellular-level morphological alterations in the retinal neuroglia in eyes with epiretinal membrane (ERM). Design: Prospective cross-sectional, observational study (November 2020–May 2022). Subjects and Controls: We included 41 eyes with unilateral idiopathic ERM and 33 healthy eyes of healthy volunteers. Methods: We examined the foveal microstructures in all eyes using adaptive optics OCT (AO-OCT) with axial and lateral resolutions of 3.4 and 3.0 μm, respectively. Adaptive optics OCT images were acquired for a 2.5° (728 μm) area at the foveal center. Main Outcome Measures: Foveal microstructures on AO-OCT images, best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution units, and associations between these parameters. Results: Adaptive optics OCT imaging of healthy eyes and eyes with ERM revealed sharp hyperreflective lines of the external limiting membrane (ELM), accompanied by hyporeflective gaps, individual nuclei of the foveal cone photoreceptors, and Müller cell bodies. The arrangement of Müller cell bodies was more vertical in eyes with ERM than in normal eyes. Epiretinal membranes adhered to foveal Müller cells via the internal limiting membrane (ILM), exerting vertical traction that pulled the foveal cones anteriorly. Adaptive optics OCT also enabled visualization of outer segment (OS) discs. Hyperreflective changes in the OS discs were observed beneath the vertically thickened ellipsoid zone (EZ) in 15 eyes (36.6%) with ERM. For eyes with ERM, multiple regression analysis showed that the length from ILM to the inner border of the outer nuclear layer and the EZ thickness were significantly associated with BCVA (β = 5.3 × 10-4 and 82.7 × 10-4, respectively), with associated 95% confidence intervals of 1.3 × 10-4 to 9.3 × 10-4 (P = 0.011) and 39.0 × 10-4 to 126.5 × 10-4 (P

Purpose: To examine choroidal angiographic features in the posterior pole associated with resolution or persistency of subretinal fluid (SRF) in eyes with central serous chorioretinopathy (CSC). Design: Observational case series. Methods: Twenty-nine patients with treatment-naïve CSC were divided into two groups based on the presence or absence of SRF 3 months after the initial visit (month 3) without any treatment. Using enhanced depth imaging of widefield swept-source optical coherence tomography, the choroidal thickness (CT), vessel density (VD), and vessel diameter index (VDI) in the superotemporal and inferotemporal subfields on the temporal side of the 18-mm circle from the disc were measured at the initial visit. We calculated the vertical difference in CT and other choroidal angiographic parameters and evaluated their association with the SRF condition at 3 months. Results: The SRF-resolved and SRF-persistent groups included 10 and 19 patients, respectively. At the initial visit, sex, age, axial length, symptom duration, the logarithm of the minimum angle of resolution visual acuity, and foveal thickness were not significantly different between the two groups. The SRF status at month 3 was not associated with the vertical difference in CT and choroidal VD (P = .614, .065, respectively). However, the vertical difference in choroidal VDI was positively associated with the future presence of SRF (P = .017). Conclusions: Vertically asymmetric dilation of choroidal vessels in the posterior pole may be a vasculature feature associated with SRF from CSC and may be a good predictor of future SRF status.

Abstract The effect of trabecular meshwork (TM)-targeted minimally invasive glaucoma surgery (MIGS) on the vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) has not been established. In this prospective, longitudinal study, we investigated changes in the deep vasculature following TM-targeted MIGS using AS-OCTA for open-angle glaucoma in 31 patients. AS-OCTA images of the sclera and conjunctiva at the nasal corneal limbus were acquired preoperatively and 3 months postoperatively, and the vessel densities (VDs) of the superficial (conjunctival) and deep (intrascleral) layers were calculated. The VDs before and after MIGS were compared, and the factors associated with the change in VD following MIGS were analyzed. The mean deep VD decreased from 11.98 ± 6.80% at baseline to 10.42 ± 5.02% postoperatively (P = 0.044), but superficial VD did not change (P = 0.73). The multivariate stepwise regression analysis revealed that deep VD reduction was directly associated with IOP reduction (P

Abstract We have previously shown that Kyoto University Substances (KUSs), valosin-containing protein (VCP) modulators, suppress cell death in retinal ganglion cells of glaucoma mouse models through alterations of various genes expressions. In this study, among the genes whose expression in retinal ganglion cells was altered by KUS treatment in the N-methyl-d-aspartic acid (NMDA) injury model, we focused on two genes, endothelin-1 (Edn1) and endothelin receptor type B (Ednrb), whose expression was up-regulated by NMDA and down-regulated by KUS treatment. First, we confirmed that the expression of Edn1 and Ednrb was upregulated by NMDA and suppressed by KUS administration in mice retinae. Next, to clarify the influence of KUSs on cell viability in relation to the endothelin signaling, cell viability was examined with or without antagonists or agonists of endothelin and with or without KUS in 661W retinal cells under stress conditions. KUS showed a significant protective effect under glucose-free conditions and tunicamycin-induced stress. This protective effect was partially attenuated in the presence of an endothelin antagonist or agonist under glucose-free conditions. These results suggest that KUSs protect cells partially by suppressing the upregulated endothelin signaling under stress conditions.

Abstract We included 97 patients with unilateral rhegmatogenous retinal detachment (RRD) with posterior vitreous detachment who underwent vitrectomy, and examined pigmentary lesion (PL) characteristics around the sites of original tears using pre- and postoperative ultra-widefield scanning light ophthalmoscopy, green light fundus autofluorescence (FAF) imaging, and intraoperative digital video. If PL did not involve RRD, we used OCT to preoperatively assess any pathologic changes to the lesion. A total of 116 retinal tears (mean count, 1.2 ± 0.5; range, 1–4 per eye) were observed in the detached retina. Overall, 102 (88%), 63 (54%), 14 (12%), and 25 (22%) tears were accompanied by lattice degeneration (LD) or PL, both LD and PL, only LD, and only PL, respectively. In green FAF images, LD showed normal to mild-hyper fluorescence, whereas all PL showed hypofluorescence. On OCT, PL were located at the RPE level, while choroid abnormalities were unclear. In the retinal areas of 22 eyes, which were not affected by RRD, we observed PL without retinal tears; some were accompanied by vitreous traction and tractional retinal detachment. Pre-, intra-, and post-operative assessments of original flap tears suggested that PL might be a risk factor for RRD, developing alongside or separately from LD.

Paraneoplastic neurologic syndromes (PNS) constitute a rare group of disorders whose optimal treatment is yet to be established. We report a patient with bilateral orbital inflammation associated with PNS, who responded well to surgical resection of the primary tumor. An 83-year-old woman was referred to our department for treatment of a progressive reduction in visual acuity and palpebral swelling in both eyes for the past 2 months. She was scheduled to undergo thoracic surgery for lung cancer. The best-corrected visual acuity (BCVA) in the right and left eye had worsened from 0.3 to 0.5 one month before she was referred to our department to 0.03 and 0.07, respectively. A slit-lamp examination revealed edema in both eyelids. Goldmann perimetry revealed several paracentral scotomas with constriction of the peripheral visual fields of both eyes, along with central absolute scotomas in V-4e isopter in the right eye. Magnetic resonance imaging revealed swelling of the bilateral extraocular muscles, which compressed the bilateral optic nerves at the orbital apex. Seven days after the resection of the lung cancer, the BCVA improved to 0.07 and 0.15 in the right and left eyes, respectively, without concomitant immunotherapy. Intravenous methylprednisolone (500 mg/day) was administered for 3 days to treat the residual orbital inflammation. Fourteen days after surgery, the BCVA further improved to 0.4 and 0.5 in the right and left eyes, respectively. Swelling of the bilateral extraocular muscles and the visual field abnormalities improved dramatically. Early diagnosis is crucial for the management of PNS.

Abstract Anti-vascular endothelial growth factor treatment for macular edema secondary to branch retinal vein occlusion generally provides good visual acuity (VA) improvement but may require repeated injections for years. To reduce the number of patients who suffer from avoidable VA loss caused by treatment drop-out, providing prospects of the correlation between expected vision improvement and required number of injections at the early stages of treatment may be helpful. In this post hoc analysis of the phase IV, randomized, open-label ZIPANGU study, we investigated the correlation between the data from Month 2 and Month 12 in terms of VA and required ranibizumab injection numbers. Fifty-nine patients were evaluated (ranibizumab monotherapy, 29; combination therapy, 30). In the monotherapy group, patients who received 1 and 3 injections by Month 2 received a mean total of 2.8 and 8.3 injections during the year, respectively. Data from the combination group were similar. The correlation coefficients for VA scores at Months 2 and 12 were 0.60 and 0.51 for the monotherapy and combination groups, respectively (both p

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

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

Abstract The aim of this retrospective, observational study was to examine the intraretinal locations of ruptured retinal arterial macroaneurysms (RMAs) and investigate the associations with the visual prognosis. Fifty patients (50 eyes) with untreated RMA rupture who visited the Department of Ophthalmology at Kyoto University Hospital (April 2014–July 2019) were included. The intraretinal position of the ruptured RMAs relative to the affected retinal artery was examined using optical coherence tomography (OCT) and color fundus photography (CFP). The relative RMA positions were anterior to (anterior type, 44%), at the same level as (lateral type, 20%), or posterior to (posterior type, 34%) the affected artery. At the initial visit, the posterior type showed greater subretinal hemorrhage thickness than did the lateral and anterior types (P = 0.016 and 0.006, respectively), and poorer visual acuity (VA) than did the anterior type (P = 0.005). At the final visit, the length of the foveal ellipsoid zone band defect was longer (P = 0.005) and VA was poorer (P

Abstract The retinal pigment epithelium (RPE) is essential for the survival and function of retinal photoreceptor cells. RPE dysfunction causes various retinal diseases including age-related macular degeneration (AMD). Clinical studies on ES/iPS cell-derived RPE transplantation for RPE dysfunction-triggered diseases are currently underway. Quantification of the diseased RPE area is important to evaluate disease progression or the therapeutic effect of RPE transplantation. However, there are no standard protocols. To address this issue, we developed a 2-step software that enables objective and efficient quantification of RPE-disease area changes by analyzing the early-phase hyperfluorescent area in fluorescein angiography (FA) images. We extracted the Abnormal region. This extraction was based on deep learning-based discrimination. We scored the binarized extracted area using an automated program. Our program’s performance for the same eye from the serial image captures was within 3.1 ± 7.8% error. In progressive AMD, the trend was consistent with human assessment, even when FA images from two different visits were compared. This method was applicable to quantifying RPE-disease area changes over time, evaluating iPSC-RPE transplantation images, and a disease other than AMD. Our program may contribute to the assessment of the clinical course of RPE-disease areas in routine clinics and reduce the workload of researchers.

PurposeTo examine whether extended interscan time (IST) on optical coherence tomography angiography (OCTA) can detect slow retinal blood flow, which is undetectable on default IST, in the healthy macula.MethodsOCTA (OCT-A1, Canon Inc.) scanning of a macular area measuring 4 × 4 mm2 of 14 healthy eyes of 14 healthy volunteers with no history or evidence of systemic and macular diseases was performed. ISTs were set at 7.6 (IST7.6, default setting), 12.0 (IST12.0), and 20.6 msec (IST20.6). Ten OCTA images were acquired at each IST, and an averaged image was created. For each averaged OCTA image obtained at IST7.6, IST12.0, and IST20.6, we defined the area surrounded by the innermost capillary ring as the foveal avascular zone (FAZ). We qualitatively evaluated the delineation of the capillaries consisting of the FAZ and quantitatively measured the FAZ area at each IST.ResultsExtensions from IST7.6 to IST12.0 and IST20.6 could newly delineated retinal capillaries that were undetectable at the default IST; new capillaries were detected in 10 (71%) eyes at IST12.0 and 11 (78%) eyes at IST20.0. The FAZ areas were 0.334 ± 0.137 mm2, 0.320 ± 0.132 mm2, and 0.319 ± 0.129 mm2 for IST7.6, IST12.0, and IST20.0, respectively; the FAZ areas at IST12.0 and IST20.0 were significantly decreased compared with that at IST7.6 (p = 0.004 and 0.002, respectively).ConclusionIn OCTA for healthy participants, extensions of the ISTs newly detected retinal capillaries with slow blood flow around FAZ. The FAZ shapes varied with different ISTs. Thus, the blood flow dynamics are not physiologically uniform around FAZ. Compared with conventional OCTA, this protocol enables a more detailed evaluation of retinal circulation and provides a better understanding of the physiological circulatory status of the healthy retina, and may enable the assessment of circulation in the very early stages in diseased eyes.

Abstract Optical coherence tomography angiography (OCTA) is a new technique for non-invasive imaging of blood vessels, allowing combined evaluation of both deep and surface vessels. The purpose of this study was to evaluate the post-trabeculectomy longitudinal changes in complete avascular area (CAA) of filtering blebs using anterior segment (AS-) OCTA and their association with surgical outcomes. This study included 57 eyes of 53 patients who had undergone trabeculectomy with mitomycin C. AS-OCTA images of filtering bleb were acquired at 3 and 6 months after trabeculectomy, and at 1 month in possible cases. CAAs, regions where complete blood flow was not depicted in AS-OCTA images, were evaluated for their presence, extent, and change over time. CAAs were detected in 37 eyes (65%) and 33 eyes (58%) at 3 and 6 months postoperatively, respectively. The extent of CAAs reduced over time after surgery in most cases. No parameters related to CAAs were significantly associated with surgical success (i.e., intraocular pressure (IOP) ≤ 12 mmHg and IOP reduction > 20% without medication). In conclusion, although it is difficult to predict surgical success by CAA itself, AS-OCTA may be useful for the objective evaluation of the vascularity of filtering blebs.

Abstract Background To quantitatively evaluate the vitreomacular interface of eyes with neovascular age-related macular degeneration (AMD) and to investigate its association with the 1-year treatment outcome following intravitreal injections of aflibercept (IVA). Methods This prospective observational case series included 59 eyes of 59 consecutive patients with treatment-naïve neovascular AMD who were treated with three monthly IVA and subsequent four bi-monthly IVA and were followed up for 1 year. We estimated posterior vitreous detachment at 1, 9, and 25 macular points within an area of 6 × 6 mm2 at the center of the fovea using the built-in enhanced vitreous visualization mode of swept-source optical coherence tomography. One year after the initial IVA, we classified the eyes into either wet or dry groups. Results The wet and dry groups included 12 and 47 eyes, respectively. The resistance rate against IVA was 20.3%. The 25-point interface score was higher in the wet group than in the dry group (23.0 ± 4.3 vs. 18.6 ± 9.8, P = 0.03), whereas there were no significant between-group differences in the 9-point and 1-point scores (P = 0.21, and 0.47, respectively) or in the other studied parameters. Multivariable analysis revealed that the 25-point vitreomacular interface score was strongly correlated with subfoveal choroidal thickness (P = 0.02, β = − 0.31). Conclusions Our findings suggest that wide-ranged separation of the posterior vitreous membrane from the retina induces poor response to IVA.

Purpose: To investigate the natural course of pachychoroid pigment epitheliopathy (PPE). Design: A retrospective cohort study. Subjects: From the Kyoto central serous chorioretinopathy (CSC) cohort consisting of 548 patients with CSC as of September 2020, we included consecutive unilateral patients with acute or chronic CSC between January 2013 and December 2016. Methods: All patients underwent complete ophthalmic examination, including multimodal imaging such as fundus autofluorescence, spectral-domain optical coherence tomography, and fluorescein angiography/indocyanine green angiography and/or optimal coherence tomography angiography. The fellow eyes of eyes diagnosed with CSC were screened for PPE, and their natural course was evaluated. We also evaluated the association of ARMS2 rs10490924, CFH rs800292, TNFRSF10A rs13278062, and GATA5 rs6061548 genotypes with the natural course. Main Outcome Measures: Incidence of CSC, pachychoroid neovasculopathy, and pachychoroid geographic atrophy (GA). Results: In total, 165 patients with unilateral CSC (mean age, 55.7 ± 12.6 years; female, 22.4%) were included from the Kyoto CSC cohort. Among them, 148 (89.7%) were diagnosed as having PPE in their non-CSC eye. Survival analysis revealed that 16.8% of PPE eyes developed CSC during the 6-year follow up, whereas non-PPE eyes did not. Although genetic factors did not have significant association with CSC development (P > 0.05, log-rank test), choroidal vascular hyperpermeability (CVH) and subfoveal choroidal thickness (SFCT) were significantly associated with CSC incidence (P = 0.001, log-rank test). Survival analysis showed that eyes without CVH and eyes with SFCT < 300 μm did not develop CSC during the 6-year follow-up. Pachychoroid neovasculopathy developed in only 1 eye with PPE during a follow-up of 46.4 months. Pachychoroid GA did not develop in any of the studied eyes. Conclusions: This study revealed a natural history of PPE in a relatively large Japanese cohort. Choroidal vascular hyperpermeability and SFCT were significant risk factors for the development of CSC in PPE eyes. Although the current results cannot be generalized for all eyes with PPE, these findings present an important clinical implication.

Abstract We performed a prospective, longitudinal study to investigate the association between the preoperative intrascleral vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) and surgical outcomes of trabecular meshwork-targeted micro- or minimally invasive glaucoma surgery (MIGS). We included 37 patients with primary open-angle glaucoma. Preoperative AS-OCTA images of the sclero-conjunctiva of the nasal corneal limbus were acquired in the superficial (conjunctival) and deep (intrascleral) layers. The vessel densities (VDs) of each layer were measured separately in the entire area, limbal side, and fornix area. Surgical success was determined by postoperative intraocular pressure (IOP) and IOP reduction. Twenty-three and 14 eyes were classified as having successful and unsuccessful outcomes, respectively. The deep VDs of the entire area and fornix area were significantly lower in the successful group (P = 0.031 and P = 0.009). The success rate was significantly higher for eyes with a lower deep VD than for eyes with a higher deep VD. A greater IOP reduction was significantly associated with lower deep VD in the fornix area (P = 0.022) and higher preoperative IOP (P

Abstract Currently there is no effective treatment available for osteoarthritis (OA). We have recently developed Kyoto University Substances (KUSs), ATPase inhibitors specific for valosin-containing protein (VCP), as a novel class of medicine for cellular protection. KUSs suppressed intracellular ATP depletion, endoplasmic reticulum (ER) stress, and cell death. In this study, we investigated the effects of KUS121 on chondrocyte cell death. In cultured chondrocytes differentiated from ATDC5 cells, KUS121 suppressed the decline in ATP levels and apoptotic cell death under stress conditions induced by TNFα. KUS121 ameliorated TNFα-induced reduction of gene expression in chondrocytes, such as Sox9 and Col2α. KUS121 also suppressed ER stress and cell death in chondrocytes under tunicamycin load. Furthermore, intraperitoneal administration of KUS121 in vivo suppressed chondrocyte loss and proteoglycan reduction in knee joints of a monosodium iodoacetate-induced OA rat model. Moreover, intra-articular administration of KUS121 more prominently reduced the apoptosis of the affected chondrocytes. These results demonstrate that KUS121 protects chondrocytes from stress-induced cell death in vitro and in vivo, and indicate that KUS121 is a promising novel therapeutic agent to prevent the progression of OA.

Diabetic retinopathy is a form of diabetic microangiopathy, and vascular hyperpermeability in the macula leads to retinal thickening and concomitant reduction of visual acuity in diabetic macular edema (DME). In this review, we discuss multimodal fundus imaging, comparing the pathogenesis and interventions. Clinicians diagnose DME using two major criteria, clinically significant macular edema by fundus examination and center-involving diabetic macular edema using optical coherence tomography (OCT), to determine the appropriate treatment. In addition to fundus photography, fluorescein angiography (FA) is a classical modality to evaluate morphological and functional changes in retinal capillaries, e.g., microaneurysms, capillary nonperfusion, and fluorescein leakage. Recently, optical coherence tomography angiography (OCTA) has allowed us to evaluate the three-dimensional structure of the retinal vasculature and newly demonstrated that lamellar capillary nonperfusion in the deep layer is associated with retinal edema. The clinical application of OCT has accelerated our understanding of various neuronal damages in DME. Retinal thickness measured by OCT enables us to quantitatively assess therapeutic effects. Sectional OCT images depict the deformation of neural tissues, e.g., cystoid macular edema, serous retinal detachment, and sponge-like retinal swelling. The disorganization of retinal inner layers (DRIL) and foveal photoreceptor damage, biomarkers of neurodegeneration, are associated with visual impairment. Fundus autofluorescence derives from the retinal pigment epithelium (RPE) and its qualitative and quantitative changes suggest that the RPE damage contributes to the neuronal changes in DME. These clinical findings on multimodal imaging help to elucidate the pathology in the neurovascular units and lead to the next generation of clinical and translational research in DME.

Descemet’s membrane detachment (DMD) is a rare but serious complication of phacoemulsification surgery. A small DMD may resolve spontaneously, but extensive DMD often requires intracameral injection of air, nonexpansile gases, or expansile gases. A 92-year-old man who underwent phacoemulsification and aspiration with intraocular lens placement in the right eye had significantly reduced visual acuity, with a hazy cornea after surgery. Anterior segment optical coherence tomography (AS-OCT) examination revealed extensive DMD throughout the cornea. He was treated with intracameral injection of 20% sulfur hexafluoride. As a result, the Descemet membrane was successfully reattached, and the corneal edema resolved. AS-OCT was helpful in confirming the presence and extent of DMD, provided useful information to determine the appropriate treatment, and was useful for monitoring DMD.

Purpose: To elucidate the incidence and treatment pattern of active exudative age-related macular degeneration (AMD). Design: A population-based cohort study conducted using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), a national claims database managed by the Japanese Ministry of Health, Labour, and Welfare (MHLW). Participants: The entire Japanese population aged 40 years or older (76 million people). Methods: With the permission of the MHLW, we accessed the complete NDB dataset and identified patients with newly diagnosed active exudative AMD between 2011 and 2018. The incidence of active exudative AMD was categorized by age and sex per year between 2011 and 2018; moreover, details regarding first-line therapy and number of anti-vascular endothelial growth factor (VEGF) injections per elapsed year since initial treatment were obtained and changes in treatment pattern were investigated. Main Outcome Measures: Incidence rate of active exudative AMD. Results: During the specified 8-year period, 246 064 incident cases of active exudative AMD were identified; 61.4% of these patients were men. The overall incidence rate was 40.66 per 100 000 person-years (95% confidence interval [CI], 40.49–40.82) in the general population aged 40 years or older, 53.22 (95% CI, 52.95–53.49) in men, and 29.78 (95% CI, 29.60–29.98) in women. Mean age of onset was lower in men than in women (72.51 ± 10.50 years vs. 73.90 ± 10.46 years). Among patients with newly diagnosed active exudative AMD, 92.9% received anti-VEGF injections for initial treatments, whereas 1.8% underwent combination therapy with photodynamic therapy. The number of anti-VEGF injections in the first year (0–12 months), second year (13–24 months), and third year (25–36 months) after the initial injection was 3.66 ± 2.30, 1.39 ± 2.20, and 1.23 ± 2.19, respectively. Patients who received fewer injections in the first year received fewer injections in subsequent years and vice versa. Conclusions: This is a relatively large population-based study on the detailed epidemiology and actual treatment patterns of active exudative AMD in clinical practice. Our results can be a fundamental information source to ensure healthy eyes and promote well-being for all at all ages.

Purpose: To investigate the 2-year effectiveness of reduced-fluence photodynamic therapy (rf-PDT) for chronic central serous chorioretinopathy (cCSC). Design: Retrospective cohort study. Participants: A total of 223 consecutive patients with newly diagnosed cCSC with active serous retinal detachment (SRD) were included from May 2007 to June 2017 and followed up for at least 2 years. Patients who underwent ocular treatment other than cataract surgery before the beginning of recruitment and those who had macular neovascularization at baseline were excluded. Methods: All patients underwent a comprehensive ophthalmic evaluation, including measurements of best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain OCT. An inverse probability of treatment weighting (IPTW) methodology was applied to balance 18 baseline characteristics between patients who received rf-PDT (rf-PDT group) and those who did not receive treatment (controls). Inverse probability of treatment weighting survival analysis and regression were performed. Main Outcome Measures: The proportion of patients whose BCVA at 24 months was the same or improved compared with the baseline visual acuity (VA) (VA maintenance rate). Results: A total of 155 eyes (rf-PDT group: 74; controls: 81) were analyzed. The patients’ backgrounds were well balanced after IPTW with standardized differences of < 0.10. An IPTW regression analysis revealed that the VA maintenance rate was significantly higher in the rf-PDT group than in the controls (93.6% vs. 70.9%, P

Abstract The ZIPANGU study assessed the efficacy and safety of ranibizumab as a one loading dose + pro re nata (one + PRN) regimen with/without focal/grid laser among treatment-naïve patients suffering from macular edema (ME) following branch retinal vein occlusion (BRVO). ZIPANGU was a phase IV, prospective, randomized, open-label, active-controlled, 12-month, two-arm, multicenter study. Treatment-naïve patients with visual impairment (19–73 letters) caused by ME, defined as central subfield thickness (CSFT) > 300 µm, due to BRVO were randomly assigned to ranibizumab monotherapy (n = 29) or combination therapy (ranibizumab + focal/grid short-pulse laser, n = 30). The primary endpoint was the number of ranibizumab injections. Secondary endpoints were mean changes in best-corrected visual acuity (BCVA) and CSFT, and safety. There were no statistically significant differences in the mean number of ranibizumab injections between monotherapy (4.3 injections) vs. combination (4.1 injections) therapy, or in CSFT. BCVA improvement in the monotherapy arm (22.0 letters) was better than the combination therapy arm (15.0 letters) (p = 0.035). Overall, both regimens appeared to be safe and well tolerated. One + PRN ranibizumab is safe and efficacious in treatment-naïve patients with ME secondary to BRVO. A conjunctive laser treatment did not lead to better functional outcomes or fewer ranibizumab injections.

Abstract Glaucoma is a multifactorial optic neuropathy, possibly involving vascular dysfunction, leading to the death of retinal ganglion cells and their axons. Disc hemorrhage (DH) is known to be closely associated with the widening of retinal nerve fiber layer defect (NFLD); however, it has not been well elucidated how DH affects retinal microvasculature. We aimed to investigate the association between DH history and longitudinal changes in superficial retinal microvasculature in NFLD. We enrolled 15 glaucoma patients with DH history (32 glaucomatous NFLD locations, with or without DH history). NFLD-angle, superficial retinal vessel density (VD), and decreased superficial retinal microvasculature (deMv)-angle were assessed using optical coherence tomography angiography for at least three times over time. The mean follow-up period and OCT/OCTA scan interval were 21.3 ± 5.4 months (range, 12–28) and 6.8 ± 0.4 months (range, 2–18), respectively. Linear mixed-effects models showed that the presence of DH history was significantly associated with an additional NFLD-angle widening of 2.19 degree/year (P = 0.030), VD decrease of 1.88%/year (P = 0.015), and deMv-angle widening of 3.78 degree/year (P

Abstract In glaucoma, retinal ganglion cells degenerate progressively, leading to visual field loss and blindness. Presently, the only treatment strategy for glaucoma is lowering the intraocular pressure. However, there are cases in which patients develop progressive visual field loss even though their intraocular pressures are within normal ranges. Therefore, the development of novel therapeutic strategies is an urgent endeavor. Besides high intraocular pressure, several other factors have been proposed to be associated with glaucoma progression, e.g., myopia, blood flow impairment, and amyloid β accumulation. We have previously reported that hop flower extracts possess γ-secretase inhibitory activities and reduce amyloid β deposition in the brains of Alzheimer’s disease model mice. In the current study, we showed that administration of hop flower extracts to glutamate-aspartate transporter (GLAST) knockout mice, the glaucoma model mice, attenuated glaucomatous retinal ganglion cell degeneration. Preservation of retinal ganglion cells in hop flower extract-administered mice was confirmed using optical coherence tomography, confocal scanning laser ophthalmoscopy, and retinal flatmount and histological evaluations. Hop flower extracts are, therefore, deemed a possible candidate as a novel therapeutic agent to treat glaucoma.

Summary: Retinal dystrophies (RDs) lead to irreversible vision impairment with no radical treatment. Although photoreceptor cells (PRCs) differentiated from human induced pluripotent stem cells (iPSCs) are essential for the study of RDs as a scalable source, current differentiation methods for PRCs require multiple steps. To address these issues, we developed a method to generate PRCs from human iPSCs by introducing the transcription factors, CRX and NEUROD1. This approach enabled us to generate induced photoreceptor-like cells (iPRCs) expressing PRC markers. Single-cell RNA sequencing revealed the transcriptome of iPRCs in which the genes associated with phototransduction were expressed. Generated iPRCs exhibited their functional properties in calcium imaging. Furthermore, light-induced damage on iPRCs was inhibited by an antioxidant compound. This simple approach would facilitate the availability of materials for PRC-related research and provide a useful application for disease modeling and drug discovery.

Purpose: To highlight a potential pathogenetic mechanism of retinal arterial macroaneurysm. Observations: A 79-year-old woman presented with a ruptured retinal arterial macroaneurysm in the right eye. One year after treatment, high-resolution multimodal imaging with optical coherence tomography (OCT), OCT angiography, and adaptive optics scanning light ophthalmoscope showed that a narrow passage developed in the vessel wall of the pre-existing retinal arterial macroaneurysm and another macroaneurysm had developed adjacent to the pre-existing one. Conclusions and Importance: These images suggest the pathogenesis of retinal arterial macroaneurysm (RAM) associated with crack-like changes in the retinal arterial wall, similar to pathologies seen in systemic arteries.

Purpose: To describe an unusual case of unilateral transient high myopization after pediatric strabismus surgery. Observations: A 6-year-old girl with intermittent exotropia had undergone strabismus surgery and experienced a transient decrease in best-corrected visual acuity (BCVA, from 20/20 to 20/33) with high myopization (from +0.25 D to −9.00 D). Slit-lamp microscopy showed anterior chamber inflammation and a narrow angle only in the affected eye. Anterior segment optical coherence tomography (AS-OCT) revealed ciliary body detachment, a narrow angle, a shallow anterior chamber, and an anteroposterior elongation of the crystalline lens in the affected eye. Her symptoms of blurry vision and high myopization improved 8 weeks postoperatively. AS-OCT revealed the resolution of the ciliary body detachment, an open angle, and a deep anterior chamber, with normalization of the anteroposterior length of the crystalline lens. Her BCVA recovered to 20/20 with spherical equivalence of 0 D. Conclusions and Importance: We reported on an extremely rare case of unilateral transient high myopization following strabismus surgery, which was resolved without additional surgery. This myopization was probably caused due to ciliary body inflammation.

Although strabismus is a well-known complication of glaucoma implant surgery, its surgical treatment is still challenging. We present a case with refractory strabismus after Baerveldt glaucoma implant (BGI) surgery, which was not sufficiently improved by strabismus surgery, but by removal of the BGI and fibrous adhesion. The patient was a 35-year-old woman who had multiple surgeries for secondary glaucoma. She had severe limitations of the movement of her right eye and binocular diplopia in all gaze positions after BGI surgery. Although she underwent two strabismus surgeries, the strabismus was not resolved. The surgery was performed by two specialists in glaucoma and strabismus. The BGI plate and the fibrous capsule were carefully removed. The fibrous tissue involved the muscle bellies of the inferior and particularly lateral rectus (LR) muscles and induced tight and wide adhesion between the muscle bellies and sclera. The adhesion was released after tenotomy at the insertion of the LR muscle, and the LR muscle was additionally resected by 6.0 mm. The ocular position and movement dramatically improved; however, intraocular pressure (IOP) increased immediately after the surgery. Then, Ahmed glaucoma valve implantation was performed 5 days after BGI removal. The IOP decreased and has been controlled. The improvement of ocular position and movement remained 9 months postoperatively and she obtained cosmetic satisfaction without diplopia or worsening of visual acuity. Removal of BGI and fibrous adhesion is a potential option for refractory mechanical strabismus following BGI surgery; however, it is important to prepare additional procedures for the subsequent IOP increase in advance.

Machine learning (ML) and deep learning (DL) are changing the world and reshaping the medical field. Thus, we conducted a systematic review to determine the status of regulatory-approved ML/DL-based medical devices in Japan, a leading stakeholder in international regulatory harmonization. Information about the medical devices were obtained from the Japan Association for the Advancement of Medical Equipment search service. The usage of ML/DL methodology in the medical devices was confirmed using public announcements or by contacting the marketing authorization holders via e-mail when the public announcements were insufficient for confirmation. Among the 114,150 medical devices found, 11 were regulatory-approved ML/DL-based Software as a Medical Device, with 6 products (54.5%) related to radiology and 5 products (45.5%) related to gastroenterology. The domestic ML/DL-based Software as a Medical Device were mostly related to health check-ups, which are common in Japan. Our review can help understanding the global overview that can foster international competitiveness and further tailored advancements.

Abstract Background Inherited retinal degeneration (IRD) refers to a heterogenous group of progressive diseases that cause death of photoreceptor cells and subsequent vision loss. These diseases often affect the peripheral retina, objective evaluation of which has been difficult until recently. Fundus autofluorescence (FAF) is a non-invasive retinal imaging technique that depicts the distribution of intrinsic fluorophores in the retina. The primary source of retinal autofluorescence is lipofuscin, which is contained in the retinal pigment epithelium (RPE). Excessive accumulation of lipofuscin and a window defect attributable to loss of photoreceptor pigment result in increased FAF whereas loss of the RPE results in decreased FAF. These changes can be seen during the course of IRD. Mainbody While conventional modalities are limited in their angle of view, recent technologic advances, known as wide-field and ultra-widefield FAF imaging, have enabled visualization of the far peripheral retina. Although clinical application of this technique in patients with IRD is still in its infancy, some studies have already indicated its usefulness. For example, an area with decreased FAF correlates well with a visual field defect in an eye with retinitis pigmentosa (RP) or cone-rod dystrophy. An abnormal FAF pattern may help in the diagnosis of IRD and associated diseases. In addition, female carriers of X-linked RP and female choroideremia show characteristic appearance. Conversely, absence of abnormal FAF despite severe retinal degeneration helps differentiation of cancer-associated retinopathy. Conclusion This paper reviews the principles of FAF, wide-field imaging, and findings in specific diseases. Wide-field imaging, particularly wide-field FAF, will provide further information for the characteristics, prognosis, and pathogenesis of IRD.

High resolution imaging with optical coherence tomography angiography and offset pinhole adaptive optics scanning light ophthalmoscope helped us visualize the hemodynamic and structural changes in a ruptured retinal arterial macroaneurysm in a 78-year-old woman. Intravitreal injection of anti-vascular endothelial growth factor was administered to ameliorate the condition.

Purpose: To report fundamental epidemiologic data for choroidal parameters such as choroidal thickness and index of choroidal vascularity in Japanese individuals and to evaluate their correlations with age, sex, systemic parameters, and other ocular parameters. Design: Population-based cohort study. Participants: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. Methods: All participants underwent standardized ophthalmic examinations, including OCT with enhanced depth imaging (EDI; RS-3000 Advance; Nidek). We manually segmented the choroidoscleral interface to measure subfoveal choroidal thickness (SFCT) and calculated the normalized choroidal intensity obtained with EDI (NCIEDI) and choroidal vascularity index (CVI). These are indices of choroidal brightness in OCT and reportedly represent the dilation of choroidal vessels. After summarizing the age-sex stratified distributions of SFCT, NCIEDI, and CVI, their associations with age, sex, axial length (AL), and spherical equivalent (SE) were evaluated using linear regression analysis with adjustments for possible confounders. Main Outcome Measures: Distribution of SFCT, NCIEDI, and CVI in the healthy Japanese population and their characteristics. Results: Age-sex standardized SFCT, NCIEDI, and CVI were 291.2 μm, 0.653, and 66.88%, respectively. In both men and women, SFCT was associated negatively with age (P < 0.001) and NCIEDI was associated positively with age (P < 0.001). Although both SFCT and NCIEDI did not differ significantly between men and women overall (P = 0.87 and P = 0.21, respectively), among younger participants (35–50 years of age), men showed significantly greater SFCT than women (P < 0.001). Only in men was CVI associated positively with age (P < 0.001). In the multivariable analysis, SFCT was associated significantly with age, sex, AL, SE, and the interaction term of age and sex (P < 0.001). Independent of SFCT, NCIEDI and CVI were associated significantly with age (P < 0.001). Conclusions: We report normative Japanese SFCT, NCIEDI, and CVI data using a large general Japanese cohort. The association analysis of SFCT with NCIEDI and CVI suggested that younger individuals have a more lumen-rich choroid for their choroidal thickness than older individuals.