Japanese Journal of Ophthalmology最新文献

Purpose: In the pivotal PHOTON trial of patients with diabetic macular edema (DME), aflibercept 8 mg administered every 12 (8q12) and 16 (8q16) weeks demonstrated similar visual and anatomic outcomes with no new safety signals to aflibercept 2 mg every 8 weeks (2q8). We conducted a prespecified subgroup analysis to assess the efficacy, durability, and safety of aflibercept 8 mg in the Japanese patients from PHOTON.

Study design: Prespecified subgroup analysis of the Phase 3 PHOTON trial (NCT04429503).

Methods: Adult patients with DME were randomized 1:2:1 to receive intravitreal aflibercept 2q8, 8q12, or 8q16 following initial monthly doses. Patients randomized to 8q12 and 8q16 were eligible for dose regimen modification. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at Week 48. Prespecified efficacy and safety outcomes at/through Week 48 are reported, segmented by Japan versus the rest of world (non-Japan).

Results: In the Japan and non-Japan subgroups, respectively, mean changes in BCVA were +7.0 and +9.0 (8q12), +7.4 and +7.9 (8q16), and +8.0 and +9.4 (2q8) letters at Week 48; differences in least squares means were -0.30 and -0.64 letters between 8q12 and 2q8 and +0.17 and -1.76 letters between 8q16 and 2q8; ocular treatment-emergent adverse events were reported in 32.4% and 31.6% (8q12), 35.3% and 28.8% (8q16), and 30.0% and 27.2% (2q8) of patients.

Conclusion: Improvements in BCVA at Week 48 were generally similar with aflibercept 8 mg versus 2 mg in this subgroup analysis of Japanese and non-Japanese patients with DME, suggesting that the primary findings from PHOTON may be generalized to the Japanese population.

Purpose: To evaluate the 1-year efficacy and safety of aflibercept 8 mg compared with aflibercept 2 mg in a pre-specified analysis of patients from Japan with neovascular age-related macular degeneration (nAMD) included in PULSAR.

Study design: PULSAR (NCT04423718) was a global, phase 3, randomized, double-masked, non-inferiority study of adults with nAMD. Patients were randomized 1:1:1 to receive aflibercept 8 mg every 12 weeks (8q12), or every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups.

Methods: This subgroup analysis of Japan and non-Japan cohorts from PULSAR evaluated changes from baseline in best-corrected visual acuity (BCVA), central subfield retinal thickness, durability and safety outcomes.

Results: In the Japan subgroup, least squares (LS) mean (95% CI) changes from baseline in BCVA at week 48 were +6.5 (+0.7, +12.3), +7.9 (+5.1, +10.6), and +4.7 (-0.5, +9.9) letters for patients in the 8q12 (n = 31), 8q16 (n = 33), and 2q8 (n = 33) groups, respectively. The majority of patients in the 8q12 (82.1%) and 8q16 (93.8%) groups maintained their randomized dosing intervals through Week 48. Ocular treatment-emergent adverse events were reported in 35.5%, 30.3%, and 39.4% of patients in the Japan subgroup in 8q12, 8q16, and 2q8 groups, respectively. Similar efficacy and safety results were observed in the non-Japan subgroup.

Conclusion: Aflibercept 8 mg has similar efficacy and safety to aflibercept 2 mg when administered at extended dosing intervals in both the Japan and non-Japan subgroups, consistent with the overall PULSAR results.

Background: Focal choroidal excavation (FCE) is a rare chorioretinal abnormality with unclear pathophysiology. Identifying structural alterations in the choroid may provide insights into disease progression and potential therapeutic approaches. In this study, we aimed to evaluate fibrotic tissue within secondary FCE using polarization-sensitive optical coherence tomography (PS-OCT).

Cases: Two men (aged 73 and 74 years) with secondary FCE associated with macular neovascularization (MNV) and pachychoroid spectrum disease were included.

Observations: PS-OCT revealed distinct birefringence within the excavation area and adjacent choroid. The fibrous components showed multidirectional orientation, and in both cases fibrotic tissue was consistently observed at the excavation margins. A characteristic pattern of vertically aligned fibrous elements was identified, suggesting that fibrous tissue deposition plays a role in the structural remodeling process of secondary FCE.

Conclusions: PS-OCT enables detection of fibrotic remodeling in secondary FCE, offering new insights into its pathogenesis and clinical significance. Further studies are needed to clarify the clinical implications of these findings and their potential role in disease management.

Purpose: To investigate the clinical features and biomarkers associated with intraocular inflammation (IOI) following brolucizumab treatment in Asian switched neovascular age-related macular degeneration (nAMD) patients.

Study design: Multi-center, retrospective cohort study.

Methods: This study included 109 eyes from 93 nAMD patients switched from other anti-vascular endothelial growth factor (VEGF) agents to brolucizumab (Beovu) without loading. Baseline characteristics, IOI timing, initial symptoms, and risk factors were assessed.

Results: IOI was observed in 17 eyes from 14 patients, including anterior uveitis (AU, n = 7), intermediate uveitis (IU, n = 5), and panuveitis with or without retinal vasculitis (RV, n = 5). Two eyes were asymptomatic. The median duration for IOI onset was 26 days, with 11 of 17 eyes (82.4%) developing IOI before the third brolucizumab injection. Firth-penalized multivariate Cox regression analysis depicted that the total number of anti-VEGF injections within one year prior to brolucizumab initiation (HR = 1.4, p = 0.009) and retinal angiomatous proliferation (RAP) (HR = 10.9, p = 0.009), may be associated with IOI development. In contrast, baseline macular neovascularization (MNV) size and the presence of retinal pigment epithelial and outer retinal atrophy were not associated with IOI occurrence.

Conclusion: Vigilant examination after the initial brolucizumab injections is critical. Patients with identified risk factors may need meticulous monitor following brolucizumab injections.

Purpose: To compare real-world outcomes between first-generation iStent (G1) and iStent inject W (G2) combined with cataract surgery.

Study design: Retrospective, propensity score-matched clinical investigation.

Methods: Consecutive eyes treated with phaco-iStent (G1) or phaco-iStent inject W (G2) were matched 1:1 (n=115 per group) for age, preoperative intraocular pressure (IOP), medication score, axial length, and glaucoma subtype. Longitudinal changes in IOP and medication score were analyzed using linear mixed models. Surgical success was evaluated by Kaplan-Meier analysis under three prespecified criteria (A/B/C), and Cox models were used to estimate hazard ratios (HRs). Corneal endothelial cell density (ECD) and perioperative complications were recorded.

Results: The baseline characteristics were balanced after matching. IOP decreased significantly from baseline at all visits in both groups except G1 at 24 months; the time-averaged IOP during follow-up was lower in G2 than in G1 (Δ=0.46 mmHg; p=0.018). The medication scores decreased postoperatively in both groups. Kaplan-Meier survival did not differ between devices (log-rank p=0.59, 0.996, and 0.509 for criteria A, B, and C, respectively). Lower preoperative IOP was consistently associated with higher failure risk according to Cox models. The generation effect was not significant, although a nonsignificant trend toward greater G2 benefit at lower IOP was observed under criterion A. The perioperative complication rates were similar.

Conclusion: Both devices provided moderate reductions in IOP and medication burden with favorable safety. G2 achieved a statistically significant but small reduction in mean IOP over time, while the time-to-failure outcomes were comparable. Baseline IOP strongly influences success, underscoring the importance of patient selection.

Purpose: To evaluate real-world adherence to anti-vascular endothelial growth factor (VEGF) therapy among Japanese patients with diabetic macular edema (DME) and identify demographic, clinical, and socioeconomic factors associated with treatment discontinuation.

Study design: Retrospective, observational cohort study.

Methods: This study included 380 treatment-naïve patients with center-involved DME. Patients were categorized into continuation (those who maintained therapy) and self-discontinuation (those who discontinued therapy after at least one follow-up visit) groups. All patients were treated under a treat-and-extend regimen with one of five anti-VEGF agents (ranibizumab, aflibercept, brolucizumab, faricimab, or ranibizumab biosimilar) between January 2017 and December 2023. Univariate and multivariate logistic regression analyses identified independent predictors of treatment discontinuation. Pre- and post-treatment visual acuity and anatomic outcomes were assessed.

Results: Among 380 patients, 55 (14.5%) self-discontinued therapy. Younger age and poorer baseline best-corrected visual acuity were significantly associated with treatment discontinuation in both univariate and multivariate analyses. Furthermore, faricimab use increased the risk of discontinuation, whereas aflibercept use was associated with better adherence.

Conclusion: The findings of this study underscore the importance of individualized patient management strategies to enhance long-term adherence to anti-VEGF therapy among patients with DME.

Refractory inflammatory ocular diseases-uveitic macular edema (UME), acute retinal necrosis (ARN), and vitreoretinal lymphoma (VRL)-pose significant diagnostic and therapeutic challenges due to their vision- or life-threatening nature and limited treatment options. UME, a leading cause of vision loss in intermediate, posterior, and panuveitis, affects approximately 40% of such cases, particularly in elderly patients and those with prolonged inflammation. Despite its prevalence, effective treatment is still being explored. ARN, caused by herpes viruses such as herpes simplex virus (HSV)-1, HSV-2, and varicella-zoster virus, ranks among the retinal diseases with the poorest visual prognosis; nearly half of patients experience a visual acuity (VA) of ≤ 0.1 within six months. However, a standardized treatment regimen has not yet been established. VRL, one of the ocular malignancies with the lowest overall survival rate, is frequently misdiagnosed as uveitis. Given the diagnostic delay and high frequency (60-85%) of central nervous system involvement-which is often directly life-threatening-early detection and comprehensive systemic management are essential. This review highlights recent advances in the diagnosis, clinical trials, and management of these three challenging ocular inflammatory diseases, emphasizing unmet needs and emerging therapeutic strategies.

Background:  Omidenepag isopropyl is a selective prostanoid prostaglandin E receptor2 agonist; its association with macular edema has mainly been identified in pseudophakic eyes. Herein, we report a case of diffuse bilateral macular edema caused by omidenepag isopropyl use in phakic eyes with a history of laser peripheral iridotomy.

Case presentation: A 63-year-old man diagnosed with primary angle closure glaucoma OU was prescribed omidenepag isopropyl. He had undergone laser iridotomy approximately 3 years prior to the omidenepag isopropyl prescription. After 4 months of using omidenepag isopropyl, he presented with blurred vision OU. Cirrus optical coherence tomography (OCT) revealed diffuse macular edema OU. Omidenepag isopropyl usage was discontinued, and bromfenac sodium hydrate was administered twice daily. After 2 months, the patient's visual discomfort improved, and a subsequent OCT examination confirmed a resolution of the macular edema.

Conclusions:  We report a case of diffuse bilateral macular edema development after omidenepag isopropyl use in a patient with glaucoma who had undergone bilateral laser peripheral iridotomy. This case demonstrates that macular edema can develop following the use of omidenepag isopropyl, even in phakic eyes. Notably, unlike most previous reports where the edema was typically cystoid in nature, this case showed diffuse retinal thickening with a preserved retinal contour. Given diffuse macular edema may affect the measurement of circumpapillary retinal nerve fiber layer (cpRNFL) thickness, caution is warranted whenever the use of omidenepag isopropyl in the management of glaucoma is considered.

Purpose: To investigate whether higher-order aberrations (HOAs) in the anterior and posterior corneal surfaces and the entire eye vary with age.

Study design: A prospective, cross-sectional study.

Methods: One hundred eyes from 100 participants, with 20 eyes per decade group (20s to 60s+), were assessed. Participants had no ocular diseases except refractive errors and mild cataracts, and no abnormalities on the anterior corneal surface, as assessed by Placido-based corneal topography. Corneal and ocular wavefront aberrations were measured with an integrated Scheimpflug tomographer/Hartmann-Shack wavefront aberrometer and analyzed over a 4-mm pupil. The root mean square values for total HOAs, spherical aberrations (SAs), and coma were calculated from the Zernike coefficients up to the 6th order. The total HOAs, SAs, and comas from the anterior corneal surface, posterior corneal surface, total cornea, and whole eye were compared across the age groups. The correlations between HOAs and age were also evaluated.

Results: Significant positive correlations with age were observed for the total HOAs and SAs in the anterior cornea (R=0.27, 0.29; P<0.01), total cornea (R=0.31, 0.34; P<0.01), and whole eye (R=0.48, 0.39; P<0.01). No significant correlations were found for coma in any region. Similarly, no significant correlations were observed for the total HOAs, SAs, or coma in the posterior cornea.

Conclusion: Total HOAs and SAs in the anterior cornea, total cornea, and whole eye were significantly positively correlated with age, whereas coma exhibited no age-related changes. These findings underscore the importance of considering age-related optical changes in clinical evaluations.

Purpose: To characterize the clinical features of open globe injury (OGI) in Vietnam and to identify risk factors associated with evisceration STUDY DESIGN: Prospective observational study METHODS: Ninety-two patients with OGI who presented to Cho Ray Hospital from August 2024 to May 2025 were prospectively enrolled. The demographic and clinical data were collected at presentation. Multivariable Firth logistic regression was used to identify independent predictors of evisceration.

Results: The majority of the patients were male, 78.3%, with a mean age of 39.5 years. Road traffic accidents were the most common cause of OGI. In those aged younger than 20 years, explosions were most frequent, whereas domestic incidents were more common in those aged older than 40 years. More than half of the eyes presented with no light perception. Evisceration was performed in 16.3% of the eyes. On multivariable analysis, zone III injury was associated with higher odds of evisceration (aOR 8.46, 95% CI 2.02-51.8), and increasing age was also associated with OGI (aOR per year 1.05, 95% CI 1.01-1.10). Trauma type, mechanism, and eyelid laceration were not associated with OGI.

Conclusion: OGIs in Vietnam predominantly affect working-age males and are often caused by high-energy trauma such as motorcycle crashes and workplace incidents. Whilst the injuries were often severe, most eyes were anatomically salvaged. Zone III injury and older age were associated with increased risk of evisceration. These findings support the need for targeted prevention efforts and improved access to specialized eye trauma care in similar settings.