Adaptive Optics Optical Coherence Tomography Analysis of Induced Pluripotent Stem Cell-Derived Retinal Organoid Transplantation in Retinitis Pigmentosa.

This study evaluates the transplantation of induced pluripotent stem cell (iPSC)-derived retinal organoids into patients with advanced retinitis pigmentosa using adaptive optics optical coherence tomography (AO-OCT) to monitor retinal changes over two years post transplantation. Our results confirmed successful engraftment and increased retinal thickness, with AO-OCT providing detailed visualization of cellular structures such as an outer plexiform layer-like line and highly reflective particles within rosette-like formations, indicative of photoreceptor development. Immunohistological analysis in a parallel monkey model confirmed these structures as mature, functional photoreceptor rosettes. The integration of high-resolution AO-OCT with immunohistology provides critical insights into the structural and functional outcomes of transplantation and represents a promising advancement in the treatment of retinal degenerative diseases.

Differences between pathologic and non-pathologic high myopia in 4-year outcomes of anti-VEGF therapy for macular neovascularization.

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, ß = 0.46) and PM groups (P < 0.001, ß = 0.59). In conclusion, over the 4-year observation period, the BCVA course after anti-VEGF therapy for myopic MNV was similar in the eyes with non-PM and those with PM; however, more additional injections in a PRN regimen were required in the eyes with non-PM compared to those with PM. Thus, more frequent and careful follow-up is required for the eyes with non-PM compared with those with PM to maintain long-term BCVA.

Short-Term Outcomes of 3 Monthly intravitreal Faricimab On Different Subtypes of Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the efficacy and safety of faricimab injections for treatment-naïve neovascular age-related macular degeneration (nvAMD) patients, including subtypes and pachychoroid phenotypes, and identify predictive factors for visual outcomes. Methods: nvAMD patients were prospectively recruited, receiving three monthly faricimab (6 mg) injections. Best-corrected visual acuity (BCVA) two months after the last injection (month 4) was compared between subtypes, and between pachychoroid neovasculopathy (PNV) and non-PNV eyes. Regression analysis determined factors influencing month 4 BCVA. Results: The study involved 23 patients (12 typical AMD [tAMD], 10 polypoidal choroidal vasculopathy [PCV], 1 retinal angiomatous proliferation [RAP]). Eleven exhibited PNV phenotype. Significant BCVA (P = 4.9 × 10-4) and central retinal thickness (CRT) (P = 1.3 × 10-5) improvements were observed post-faricimab treatment. The therapy demonstrated favourable results for both tAMD and PCV eyes, and non-PNV and PNV eyes. Faricimab achieved dry macula in 77.3% of eyes, with subretinal fluid resolution in most cases, although intraretinal fluid (IRF) often persisted. Multivariable analysis identified external limiting membrane (ELM) presence and IRF as BCVA contributors at month 4. Conclusion: Faricimab demonstrated significant effectiveness and safety in treatment-naïve nvAMD patients, particularly for PCV and PNV eyes. ELM presence and IRF is predictive of visual outcomes.

Japan-epiretinal membrane (J-ERM) registry: A prospective cohort study protocol investigating the surgical outcome of epiretinal membrane.

BACKGROUND: Epiretinal 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 DESIGN: This 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. DISCUSSION: The results of this study will support the surgical decisions and procedures in ERM practices.

Therapeutic effects of faricimab on aflibercept-refractory age-related macular degeneration.

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.

Hemodynamic predictors of negative false lumen remodeling after frozen elephant trunk for acute aortic dissection.

OBJECTIVE: We evaluated the blood flow within the downstream aortic false lumen after frozen elephant trunk repair for acute aortic dissection and identified hemodynamic predictors of false lumen expansion and negative false lumen remodeling using four-dimensional flow magnetic resonance imaging. METHODS: Thirty-one patients (Stanford type A, n = 28; Stanford type B, n = 3) with patent false lumen who underwent frozen elephant trunk procedures for acute aortic dissection were included in this observational study. Each patient underwent computed tomography during the follow-up period and four-dimensional flow magnetic resonance imaging within 3 postoperative months. The false lumen volumetric expansion rate was calculated using computed tomography data. The direction and the rate of flow in the lower descending aortic false lumen were analyzed. Negative false lumen remodeling was defined as a volumetric increase of > 10% from the baseline volume. RESULTS: Negative false lumen remodeling had developed in 6 of the 31 patients during the observation period. Most of the false lumen flows were biphasic during systole. The range between peak and nadir flow rates was associated with the false lumen volumetric expansion rate (ß coefficient = 6.77; p < 0.01, R2 = 0.43). CONCLUSIONS: The range between peak and nadir flow rates may serve as a hemodynamic predictor of negative false lumen remodeling, enabling further treatment for patients at risk of expansion in the downstream aorta.

A case of Epstein-Barr virus-associated primary vitreoretinal lymphoma in an immunosuppressed patient.

PURPOSE: To describe a rare case of Epstein-Barr virus (EBV)-positive primary vitreoretinal lymphoma (PVRL) in an immunosuppressed patient. METHODS: Observational case report. RESULTS: A 64-year-old man under immunosuppressive therapy for rheumatic arthritis was referred for 2-month of blurred vision and decreased visual acuity in the right eye. Only mutton-fat keratic precipitates and mild vitreous opacity were found in the right eye without (sub-)retinal or sub-retinal pigment epithelial lesions. Vitreous biopsy and systemic workup suggested the diagnosis of PVRL of diffuse large B cell lymphoma (DLBCL) subform. Neoplastic cells stained positive for EBV antigens, EBV-encoded small RNA and Epstein-Barr nuclear antigen 2, consistent with EBV-positive DLBCL. Intravitreal methotrexate was effective in improving ocular symptoms. CONCLUSION: Our case provided evidence on the association of EBV infection with PVRL.

Evaluation of the Efficiency and Safety of a 27-Gauge 20,000 Cuts per Minute Vitreous Cutter.

Purpose: The aim of this study was to evaluate the efficiency and safety of a 27-gauge (G) 20,000 cuts per minute (cpm) vitreous cutter in clinical settings. Patients and Methods: This was a retrospective and observational study of 40 eyes of 40 patients with idiopathic epiretinal membrane (ERM). Twenty patients (20 eyes) were treated using a 27G 10,000-cpm vitreous cutter (Advanced ULTRAVIT® Probe, Alcon), whereas the remaining 20 patients (20 eyes) were treated using a 27G 20,000-cpm cutter (Hypervit® dual-blade probe, Alcon). All the surgeries were performed by the same surgeon (YM). The time from the start of vitrectomy to the start of ERM peeling was independently measured by two separate examiners using digital videos of each surgery. The average duration of vitrectomy was calculated for each patient. Additionally, the data of the patients in the two groups were extracted from their medical and surgical records and compared. Results: The time from the initiation of vitrectomy until the start of ERM peeling was 184 ± 56.9 and 152 ± 39.5 s for the 10,000-cpm and 20,000-cpm groups, respectively. The duration of vitrectomy was significantly shorter in the 20,000-cpm group than in the 10,000-cpm group (p = 0.041). Postoperative vitreous hemorrhage was observed in one patient in the 10,000-cpm group, whereas no complications were observed in the 20,000-cpm group. Conclusion: In a clinical setting, the 27G 20,000-cpm vitreous cutter may have a higher safety profile and higher efficacy for vitreous removal than that of the 27G 10,000-cpm vitreous cutter.

PREDICTORS OF 3-MONTH AND 1-YEAR VISUAL OUTCOMES AFTER VITRECTOMY WITH SUBRETINAL TISSUE PLASMINOGEN ACTIVATOR INJECTION FOR SUBMACULAR HEMORRHAGE.

PURPOSE: To investigate factors associated with 3-month or 1-year best-corrected visual acuity (BCVA) after vitrectomy with subretinal tissue plasminogen activator injection for submacular hemorrhage (SMH) and to identify the predictors of early displacement. METHODS: This prospective cohort study included consecutive eyes with SMH complicating neovascular age-related macular degeneration or retinal macroaneurysm that underwent vitrectomy with subretinal tissue plasminogen activator injection and were followed up for at least 3 months. Parameters that correlated with 3-month BCVA, 1-year BCVA, and 2-week displacement grade (0-3) were identified. RESULTS: Twenty-nine eyes of 29 patients (73.1 ± 8.4 years; neovascular age-related macular degeneration, 25 eyes) were included. Logarithm of the minimum angle of resolution BCVA improved 3 months after the surgery (baseline, 0.76 [20/115] ± 0.35; 3-month, 0.51 [20/65] ± 0.32; P = 0.006). In multivariable analyses, 1-year logarithm of the minimum angle of resolution BCVA correlated with age ( P = 0.007, ß = 0.39) and SMH recurrence within 1 year after surgery ( P < 0.001, ß = 0.65). Two-week displacement grade correlated with the contrast-to-noise ratio of SMH ( P = 0.001, ß = -0.54). Macular hole occurred in three eyes (10%) with small SMH size and was closed in all eyes via additional vitrectomy with an inverted internal limiting membrane flap technique. CONCLUSION: The recurrence of SMH negatively affected the 1-year visual outcome after vitrectomy with subretinal tissue plasminogen activator injection for SMH. The contrast-to-noise ratio was a useful predictor of early SMH displacement, but not of 1-year BCVA. Further research is necessary to determine the optimal treatment to prevent SMH recurrence.

TEN-YEAR VISUAL OUTCOME AND CHANGE IN CHORIORETINAL ATROPHY AFTER INTRAVITREAL RANIBIZUMAB FOR MACULAR NEOVASCULARIZATION IN PATHOLOGIC MYOPIA.

PURPOSE: To investigate the 10-year visual outcome and chorioretinal atrophy after a single intravitreal ranibizumab injection followed by a pro re nata regimen for myopic macular neovascularization in pathologic myopia, and to identify the factors associated with 10-year best-corrected visual acuity (BCVA). METHODS: This retrospective observational study evaluated 26 consecutive treatment-naïve eyes (26 patients) with myopic macular neovascularization in pathologic myopia who underwent a single intravitreal ranibizumab followed by a pro re nata regimen of intravitreal ranibizumab and/or intravitreal aflibercept injection and observed over 10 years. We assessed changes in BCVA and morphological parameters, including the META-PM Study category as a chorioretinal atrophy index. RESULTS: The logarithm of the minimum angle of resolution BCVA changed from 0.36 (Snellen, 20/45) ± 0.39 to 0.39 (20/49) ± 0.36 over 10 years of observation. Compared to baseline, 1-year BCVA improved ( P = 0.002), whereas 2 to 10-year BCVA was not significantly different. Total injection frequency was 3.8 ± 2.6. In none of the eyes, 10-year BCVA was 20/200 or less. Ten-year BCVA correlated with baseline BCVA ( P = 0.01, r = 0.47). The META-PM Study category progressed in 60% of eyes. There were no drug-induced complications. CONCLUSION: Best-corrected visual acuity in eyes with myopic macular neovascularization in pathologic myopia was maintained for 10 years after a single intravitreal ranibizumab followed by a pro re nata regimen without drug-induced complications. The META-PM Study category progressed in 60% of eyes, especially those with older baseline age. Early diagnosis and treatment of myopic macular neovascularization are essential to maintain good long-term BCVA.

Binocular metamorphopsia in patients with branch retinal vein occlusion: a multi-center study.

PURPOSE: The pathology of branch retinal vein occlusion (BRVO), a retinal circulatory disease, is related to monocular metamorphopsia-related vision impairment of the affected eyes, but the association of binocular metamorphopsia in such patients is unclear. This study aimed to examine the frequency of binocular metamorphopsia and its association with the clinical characteristics of patients with BRVO. METHODS: A total of 87 patients who were treated for BRVO-associated macular edema (ME) were included in this study. At baseline and 1 and 3 months after the initiation of anti-vascular endothelial growth factor (VEGF) treatment, we quantified metamorphopsia in the affected eyes and binocular metamorphopsia using the M-CHARTS® diagnostic tool. RESULTS: At baseline, 53 and 7 patients had metamorphopsia in the affected eyes and binocular metamorphopsia, respectively. Although the visual acuity improved significantly after the initiation of anti-VEGF treatment, the mean M-CHARTS score in the affected eyes did not change from the baseline score. At 3 months, 9 patients showed binocular metamorphopsia; it was significantly associated with metamorphopsia in the affected eyes with a 95% confidence interval of 0.021-0.122 (ß = 0.306, p = 0.006). CONCLUSION: Metamorphopsia in the affected eyes can cause binocular metamorphopsia in patients with BRVO-ME.

A Rare Case of Blindness Caused by Syphilis with Malignant Hypertensive Nephropathy.

The number of patients with syphilis has been rapidly increasing. Without treatment, syphilis can damage various organs and become life-threatening. We herein report a 29-year-old woman diagnosed with neurosyphilis, acute hydrocephalus, syphilitic uveitis combined with hypertensive retinopathy, and malignant hypertensive nephropathy. To our knowledge, this is the first report of syphilis complicated with malignant hypertensive nephropathy proven by a renal biopsy. Neurosyphilis was successfully treated with intravenous penicillin G, and severe hypertension subsequently resolved. However, delayed medical examinations and complications of syphilitic uveitis and hypertensive retinopathy resulted in irreversible visual loss. To prevent irreversible organ damage, early treatment is essential.

Novel Manifestation of Retinal Hemangioblastomas Detected by OCT Angiography in von Hippel-Lindau Disease.

PURPOSE: To elucidate the clinical characteristics of atypical retinal vascular proliferation in patients with von Hippel-Lindau (VHL) disease using OCT angiography (OCTA). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-seven consecutive patients with a diagnosis of VHL disease who visited Kyoto University Hospital between January 2019 and March 2022. METHODS: Retinal hemangioblastomas (RHs) were assessed using multimodal imaging including OCTA. Retinal hemangioblastomas were classified into 2 phenotypes: nodular and flat. Nodular RHs were defined as typical RHs that were globular, well-circumscribed tumors, often accompanied with dilated feeder arterioles and draining venules. Flat RHs lacked a protruded red or colored mass, had variable and indistinct borders, and were not accompanied with feeder and draining vessels. MAIN OUTCOME MEASURES: The prevalence, distribution, and description of atypical flat RHs. RESULTS: Among 57 consecutive patients with VHL disease, 37 patients (64.9%) showed RHs in at least 1 eye. Bilateral RHs were seen in 23 patients (62.2%). Among 58 eyes of 37 patients with RHs, typical nodular RHs were detected in 54 eyes. Nodular RHs were seen mainly in the peripheral retina and occasionally in the peripapillary region, and they showed exudative changes in some cases. Flat RHs were detected in 7 eyes (12.1%). Four eyes showed only flat RHs, and 3 eyes showed both types in the same eye. Most flat RHs appeared as retinal hemorrhages or faint flat abnormal retinal vessels in the inner retina on the fundus examination, often within the macula area or peripapillary. In all eyes with flat RHs, OCTA showed abundant blood flow in the lesions. OCT revealed that flat RHs were seen mainly between the retinal nerve fiber layer and the ganglion cell layer, and occasionally within the inner nuclear layer. During a mean follow-up period of 20.4 ± 15.0 months, no flat RHs accompanied exudative change, tractional retinal detachment, or progression in size. CONCLUSIONS: Patients with VHL disease can demonstrate 2 distinct types of RHs: the classic nodular type and an atypical flat type. OCT angiography can be useful in improving the detection of atypical flat RHs, which can be difficult to detect clinically. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Seven-year outcome after 1-year fixed regimen of intravitreal aflibercept injections followed by pro re nata treatment for neovascular age-related macular degeneration.

PURPOSE: The study aims to investigate the 7-year best-corrected visual acuity (BCVA) course after 1-year fixed regimen of intravitreal aflibercept injection (IVA) for neovascular age-related macular degeneration (nAMD) and to identify factors affecting this BCVA. METHODS: This longitudinal, observational study included 63 treatment-naïve eyes (61 patients) with nAMD, treated with 1-year fixed regimen of IVA-3 monthly injections and 4 subsequent bimonthly injections-essentially followed by PRN regimen of IVA but sometimes followed by agent switching, photodynamic therapy (PDT), or vitrectomy, as needed. We assessed BCVA changes over a 7-year period. Morphologically, we assessed central retinal thickness (CRT), central choroidal thickness (CCT), subfoveal pigment epithelial detachment (PED) height, vitreomacular traction/adhesion (VMT/VMA), epiretinal membrane (ERM), and macular atrophy involving the fovea. RESULTS: Logarithm of the minimum angle of resolution (logMAR) BCVA changed from 0.20 ± 0.24 to 0.29 ± 0.45 over 7 years. BCVA improved significantly after years 1 and 2 (P = 0.002 and 0.001, respectively) and then slowly decreased. BCVA after years 3-7 did not significantly differ from baseline. CRT and CCT decreased significantly during follow-up, while PED height did not. VMT/VMA decreased significantly, whereas ERM and macular atrophy increased significantly. Seven-year and baseline BCVA positively correlated (P = 0.007, ß = 0.35). CONCLUSIONS: BCVA was maintained for 7 years in nAMD eyes after 1-year fixed regimen of IVA, essentially followed by PRN regimen, but sometimes followed by agent switching, PDT, or vitrectomy, without severe drug-induced complications. Thus, early diagnosis and treatment of nAMD are essential for maintaining good long-term BCVA, even in eyes with relatively poor baseline vision.

Effect of Duration of Macular Detachment on Visual Prognosis after Surgery for Macula-Off Retinal Detachment: Japan-Retinal Detachment Registry.

PURPOSE: To evaluate the association between the duration of macular detachment (DMD) and visual prognosis in patients with macula-off rhegmatogenous retinal detachment (RD). DESIGN: Prospective observational cohort study. PARTICIPANTS: This study analyzed 719 eyes with macula-off rhegmatogenous RD registered with the Japan-Retinal Detachment Registry created by the Japan Retina and Vitreous Society. METHODS: We included patients with macular detachment without a history of prior surgery, except cataract surgery and vitrectomy. Reoperation cases, hereditary RD, and macular hole RD were excluded. We compared the visual prognosis between patients with DMD of N days or less and those with DMD of N + 1 days or more (N = 2-5). For these 4 comparisons, the inverse probability of treatment weighting (IPTW) methodology was employed, to balance 20 baseline characteristics between the shorter and longer DMD groups. The baseline characteristics included age, sex, axial length, baseline visual acuity, operative procedures, and detailed characteristics of RD. P-values < 0.01 were considered statistically significant. MAIN OUTCOME MEASURES: The best-corrected visual acuity (BCVA) 6 months after surgery. RESULTS: The final analysis included 719 eyes. For all comparisons, the patients' backgrounds were well balanced after IPTW with standardized differences < 0.10. The IPTW regression analysis revealed that the BCVA after 6 months was significantly better after surgeries for DMD of ≤ 2 days than that for DMD of ≥ 3 days. Similarly, the 6-month BCVA for surgeries for DMD of ≤ 3 days was significantly better than that for surgeries for DMD of ≥ 4 days (differences in logarithm of the minimum angle of resolution: -0.113, P = 9.1 × 10-7; -0.076, P = 1.6 × 10-3, respectively). On the other hand, there were no statistically significant differences for the other comparisons. CONCLUSIONS: Earlier surgical treatment within 3 days from the onset of macular detachment should be considered, after accounting for social circumstances, such as weekends. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Macular atrophy at 5 years after photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To investigate predictors for macular atrophy (MA) involving the fovea after photodynamic therapy (PDT) followed by pro re nata (PRN) treatment for polypoidal choroidal vasculopathy (PCV). METHODS: This prospective observational study analysed treatment-naïve eyes with symptomatic PCV without MA at baseline which were followed up for 5 years. All eyes were initially treated with PDT, followed by a PRN regimen of anti-vascular endothelial growth factor (VEGF) therapy and/or PDT. We assigned eyes with and eyes without development of MA involving the fovea 5 years after the initial treatment into MA and non-MA groups, respectively. Baseline parameters and the number of treatments were compared between the two groups. RESULTS: Seventy-two eyes of 69 consecutive patients were included, and 29 eyes of 29 patients were analysed. Twelve (41%) and 17 (59%) eyes were assigned into the MA and non-MA groups, respectively. There were significant differences in subfoveal choroidal thickness (226.2 ± 47.8 µm vs. 278.8 ± 68.1 µm, P = 0.03) and number of anti-VEGF injections (13.7 ± 9.6 vs. 5.4 ± 5.6, P = 0.007) between the MA and non-MA groups, but not in the number of PDT sessions (P = 0.71). Best-corrected visual acuity at 5 years in the MA group was lower than in the non-MA group (P = 0.048). CONCLUSION: Our long-term observation suggests that a thin subfoveal choroid at baseline and many followed anti-VEGF injections in a PRN regimen increase the risk for development of MA involving the fovea 5 years after PDT.

Effectiveness of Reduced-fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy: A Propensity Score Analysis.

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 < 0.001, 12 months; 85.7% vs. 69.8%, P = 0.019, 24 months). The rf-PDT group tended to show better VA improvement, but was not statistically significant (-0.06 vs. -0.008, P = 0.07, 12 months; -0.06 vs. -0.03, P = 0.32, 24 months). An IPTW Cox regression showed a significantly higher rate of complete SRD remission in the rf-PDT group (hazard ratio, 5.05; 95% confidence interval, 3.24-7.89; P < 0.001). Conclusions: The study suggests the beneficial effect of rf-PDT for cCSC for both VA maintenance and higher proportion of complete SRD remission in the clinical setting.

MACULAR BLOOD FLOW CHANGES IN BRANCH RETINAL VEIN OCCLUSION EXAMINED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VARIABLE INTERSCAN TIME ANALYSIS.

PURPOSE: To examine the relationship between changes in retinal blood flow and the recurrence of macular edema in eyes with branch retinal vein occlusion. METHODS: This observational study included 32 eyes in 32 patients (18 men and 14 women) with branch retinal vein occlusion who visited the Department of Ophthalmology at Kyoto University Hospital (February 2021-November 2021). At the time of inclusion in the study, each patient underwent optical coherence tomography angiography on a macular area measuring 4 × 4 mm 2 . For variable interscan time analysis, different interscan times were set at 7.6 (IST 7.6 ) and 20.6 ms (IST 20.6 ) for the optical coherence tomography angiography. The parafoveal vessel densities were measured sectorally at IST 7.6 and IST 20.6 , and their relationship with the longitudinal changes evident in the retinal thicknesses during the variable interscan time analysis examination and 2 months later was evaluated. RESULTS: The parafoveal vessel densities in the affected sector was significantly greater at IST 20.6 than at IST 7.6 ( P = 0.011). At 2 months after the variable interscan time analysis examination, 6 patients (19%) showed recurrence of macular edema involving the fovea. The difference in the parafoveal vessel densities (IST 20.6 - IST 7.6 ) in the affected sector was significantly associated with longitudinal retinal thickening in the corresponding parafovea ( P = 0.020) and fovea ( P = 0.014). CONCLUSION: In eyes with branch retinal vein occlusion, optical coherence tomography angiography variable interscan time analysis facilitated the detection of retinal blood flow changes that might be predictive for the recurrence of macular edema.

Genome-wide Survival Analysis for Macular Neovascularization Development in Central Serous Chorioretinopathy Revealed Shared Genetic Susceptibility with Polypoidal Choroidal Vasculopathy.

PURPOSE: To identify susceptibility genes for macular neovascularization (MNV) development in central serous chorioretinopathy (CSC). DESIGN: Genome-wide survival analysis using a longitudinal cohort study. PARTICIPANTS: We included 402 and 137 patients with CSC but without MNV at their first visit from the Kyoto CSC Cohort and Kobe CSC dataset, respectively. All patients underwent detailed ophthalmic examinations, including multimodal imaging, such as fundus autofluorescence, spectral-domain OCT, and fluorescein angiography/indocyanine green angiography or OCT angiography. METHODS: We conducted a genome-wide survival analysis using the Kyoto CSC Cohort. We applied the Cox proportional hazard model to adjust for age, sex, and the first principal component. Single nucleotide polymorphisms (SNPs) with P values < 1.0 × 10-5 were carried forward to the replication in the Kobe CSC dataset. Moreover, we evaluated the contribution of previously reported age-related macular degeneration (AMD) susceptibility loci. We used FUMA and ToppFun for the functional enrichment analysis. MAIN OUTCOME MEASURES: The association between SNPs and MNV development in patients with CSC. RESULTS: Rs370974631 near ARMS2 displayed a genome-wide significant association in the meta-analysis of discovery and replication result (hazard ratio [HR]meta, 3.63; Pmeta = 5.76 × 10-9). Among previously reported AMD susceptibility loci, we additionally identified CFH rs800292 (HR, 0.39, P = 2.55 × 10-4), COL4A3 rs4276018 (HR, 0.26, P = 1.56 × 10-3), and B3GALTL rs9564692 (HR, 0.56, P = 8.30 × 10-3) as susceptibility loci for MNV development in CSC. The functional enrichment analysis revealed significant enrichment of 8 pathways (GO:0051561, GO:0036444, GO:0008282, GO:1990246, GO:0015272, GO:0030955, GO:0031420, and GO:0005242) related to ion transport. CONCLUSIONS: ARMS2, CFH, COL4A3, and B3GALTL were identified as susceptibility genes for MNV development in CSC. These 4 genes are known as susceptibility genes for AMD, whereas COL4A3 and B3GALTL were previously reported to be polypoidal choroidal vasculopathy (PCV)-specific susceptibility genes. Our findings revealed the shared genetic susceptibility between PCV and MNV secondary to CSC.

CONTRAST-TO-NOISE RATIO IS A USEFUL PREDICTOR OF EARLY DISPLACEMENT OF LARGE SUBMACULAR HEMORRHAGE BY INTRAVITREAL SF6 GAS INJECTION.

PURPOSE: To investigate predictors of early displacement of submacular hemorrhage (SMH) by simple intravitreal SF6 gas injection. METHODS: This retrospective study included 16 eyes of 16 consecutive patients (age: 74.5 ± 7.7 years; 15 men) with large SMH treated with simple intravitreal SF6 gas before inception of subretinal tissue plasminogen activator injection at our institution. The SMH displacement was graded at 1-week posttreatment as 0, 1, or 2. Central retinal thickness, central choroidal thickness, SMH height, SMH area, disease duration, use of anticoagulant or antiplatelet drugs, and contrast-to-noise ratio (CNR) of SMH on optical coherence tomography images were recorded. Correlations between displacement grading and baseline parameter were analyzed. RESULTS: Univariable correlation analysis revealed association of the 1-week displacement grading with the CNR (P = 0.004; r = -0.68) and SMH height (P = 0.03; r = -0.55). The CNR was most strongly associated with 1-week displacement on multivariable correlation analysis (P = 0.01; ß = -0.60). CONCLUSION: Findings of the present study showed that the CNR of SMH was a useful predictor of early displacement of large SMH after simple intravitreal SF6 gas injection. When vitrectomy with subretinal injection of tissue plasminogen activator is difficult in patients with large SMH, with low CNR on optical coherence tomography, simple intravitreal SF6 gas injection may be a treatment option.