Differences in collateral vessel formation after experimental retinal vein occlusion in spontaneously hypertensive rats and wild-type rats.

Objective: Retinal vein occlusion (RVO) can lead to visual impairment, but the development of collateral vessels can sometimes mitigate significant damage. This study aimed to investigate the relationship between collateral vessels and hypertension, the most common underlying condition associated with RVO, by comparing spontaneously hypertensive rats (SHRs) and wild-type Wister rats (WWRs). We also examined the differences between WWRs and SHRs in terms of sphingosine 1-phosphate receptor 1 (S1PR1) expression and its product nitric oxide synthase 3 (NOS3) expression, which are involved in the formation of collateral vessels after vascular occlusion. Methods: Laser photocoagulation (PC) was used to occlude one randomly selected retinal vein in WWRs and SHRs, and the area surrounding the occluded vessel was examined using optical coherence tomography angiography. If reperfusion of the occluded vessel occurred within 2 weeks, the vessel was re-occluded repeatedly by PC. The number of eyes with successfully occluded vessels accompanied by collateral vessels was recorded. Then, WWRs and SHRs were divided into the following four groups: 1) control (no treatment), 2) vehicle (20% DMSO), 3) S1PR1 agonist (2 mg/mL SEW2871), and 4) S1PR1 antagonist (0.25 mg/mL VPC 23019) groups. The drugs were administered intravitreally in all groups except the control. The number of laser shots required for successful RVO was recorded. Histological evaluation and quantitative real-time PCR of S1PR1 and NOS3 were performed to elucidate the mechanisms underlying collateral vessel formation. Results: The proportion of eyes achieving successful vein occlusion was lower in SHRs (4/12 eyes, 33.3%) than in WWRs (8/10 eyes, 80%, p = 0.043). NOS3 expression at 6 h after PC was significantly higher in WWRs than in SHRs (p = 0.021). In WWRs treated with SEW2871, vein occlusion failed in 7 of 10 eyes (70%). The expression of NOS3 was significantly higher in the SEW2871 treatment group than in the untreated group (p < 0.001). Furthermore, NOS3 expression was significantly higher after SEW2871 treatment in WWRs than in SHRs (p = 0.011). Conclusion: In hypertensive environments, collateral vessels are less likely to develop, and S1PR1 may be involved in this phenomenon.

Treatment strategy for BVO-ME based on long-term outcomes correlating retinal structure by OCT image and visual acuity.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (VEGF) is a mainstream treatment for reducing ME secondary to BRVO (BVO-ME). Regrettably, most reports of intravitreal anti-VEGF for BVO-ME have disclosed only short-term outcomes. Here, we characterized long-term indicators for the visual prognosis of patients with BVO-ME, including the correlation between retinal structure by OCT and visual acuity. METHODS: Patients with BVO-ME were retrospectively recruited based on clinical records in Kansai Medical University Hospital from June 2012 to March 2022. This study enrolled patients with vision loss who received intravitreal injection of anti-VEGF for BVO-ME. Inclusion criteria were that patients received intravitreal injection of anti-VEGF as their first treatment and were followed for at least 36 months. Exclusion criteria were those patients with ocular disease other than BRVO or who had been previously treated for BVO-ME. Patients were divided into two groups according to BCVA at the final visit: Group A (≥ 0.7) and Group B (< 0.7). RESULTS: Forty-seven eyes from 45 patients were assessed. The mean follow-up period from initial to final visit was 64.38 ± 15.07 (range, 38-100) months. BCVA in Group A (n = 32) was significantly greater than in Group B (n = 15) at all timepoints. The ratio that the number of eyes which the EZ band and the foveal bulge were intact in Group A was higher than in Group B (p = 0.0004 and p = 0.0002, respectively). The ratio that the number of eyes which recurrence SRD was observed by the final visit in Group A was lower than in Group B (p = 0.0485). CONCLUSIONS: The integrity of the EZ band and an intact foveal bulge were significant predictors for visual acuity. In contrast, recurrent SRD led to poor visual acuity in the long term, even if BCVA was good in the short term.

Efficacy, durability, and safety of faricimab in patients from Asian countries with neovascular age-related macular degeneration: 1-Year subgroup analysis of the TENAYA and LUCERNE trials.

PURPOSE: To evaluate 1-year efficacy, durability, and safety of faricimab among patients from Asian countries in the TENAYA/LUCERNE trials of neovascular age-related macular degeneration (nAMD). METHODS: Treatment-naïve patients with nAMD were randomly assigned (1:1) to faricimab 6.0 mg up to every 16 weeks (Q16W), based on disease activity at weeks 20 and 24, or aflibercept 2.0 mg Q8W. The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48. RESULTS: In the pooled TENAYA/LUCERNE trials, there were 120 (9.0%) and 1209 (91.0%) patients in the Asian (faricimab n = 61; aflibercept n = 59) and non-Asian country (faricimab n = 604; aflibercept n = 605) subgroups, respectively. In the Asian country subgroup, mean BCVA change from baseline at the primary endpoint visits was 7.1 (95% CI, 4.3-9.8) letters with faricimab and 7.2 (4.4-10.0) letters with aflibercept. In non-Asian country patients, mean vision gains were 6.1 (5.2-7.1) and 5.7 (4.8-6.7) letters with faricimab and aflibercept, respectively. At week 48, 59.6% of Asian country patients in the faricimab group achieved Q16W dosing (vs. 43.9% non-Asian) and 91.2% achieved ≥ Q12W dosing (vs. 77.5% non-Asian). Central subfield thickness reductions were similar between the subgroups, with meaningful and similar reductions from baseline observed at the primary endpoint visits and over time. Faricimab was well tolerated in both subgroups, with an acceptable safety profile. CONCLUSION: Consistent with the global TENAYA/LUCERNE findings, faricimab up to Q16W showed sustained visual and anatomical benefits in patients with nAMD from Asian and non-Asian countries. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03823287 (TENAYA); NCT03823300 (LUCERNE). Date of registration: January 30, 2019.

Potential for Treatment Interval Extension in Eyes with nAMD Disease Activity Post Loading Phase in HAWK and HARRIER.

INTRODUCTION: The HAWK and HARRIER studies evaluated the efficacy and safety of brolucizumab versus aflibercept in treatment-naïve eyes with neovascular age-related macular degeneration. Based on the study design, brolucizumab-treated eyes adjusted to a q8w regimen because the presence of disease activity (DA) at the end of the matched loading phase (Week 16) could not subsequently extend to a q12w interval. The aim of this post hoc analysis was to assess subsequent DA in this subgroup to determine the potential for interval extensions during the first year of treatment. METHODS: Pooled data from the brolucizumab 6 mg arms and aflibercept arms of HAWK and HARRIER were included. Presence of DA was determined by the masked investigator based on their assessment of functional and anatomical parameters measured by optical coherence tomography. DA was compared at DA assessments, conducted at Weeks 16, 20, 32, and 44; fluid was also assessed at the primary analysis at Week 48. RESULTS: Fewer brolucizumab- (22.8%) than aflibercept-treated (32.2%) eyes had DA at the first DA assessment at Week 16. In eyes with investigator-identified DA at Week 16, BCVA change from baseline to Week 96 was comparable between treatment arms. Fewer brolucizumab- than aflibercept-treated eyes had DA at each subsequent DA assessment in Year 1: 31.8% vs 39.1% (Week 20), 27.3% vs 43.5% (Week 32), and 17.3% vs 31.2% (Week 44). Fewer eyes treated with brolucizumab than aflibercept had intraretinal and/or subretinal fluid: 35.3% vs 43.5% (Week 20), 55.8% vs 69.6% (Week 32), 30.0% vs 43.1% (Week 44), and 48.6% vs 68.6% (Week 48). CONCLUSION: These findings indicate that, in eyes that still had DA 8 weeks after the final dose of loading phase, brolucizumab-treated eyes had improved fluid resolution and higher potential for treatment interval extension than aflibercept-treated eyes during the first year of treatment.

Clinical Characteristics and Progression of Geographic Atrophy in a Japanese Population.

PURPOSE: To elucidate the clinical characteristics and progression rate of geographic atrophy (GA) associated with age-related macular degeneration (AMD) in a Japanese population. DESIGN: Retrospective, multicenter, observational study. PARTICIPANTS: A total of 173 eyes from 173 patients from 6 university hospitals in Japan were included. Of 173 study eyes, 101 eyes from 101 patients were included in the follow-up group. All patients were Japanese, aged ≥ 50 years and had definite GA associated with AMD in at least 1 eye. METHODS: The GA area was measured semiautomatically using fundus autofluorescence (FAF) images. In the follow-up group followed for > 6 months with FAF images, the GA progression rate was calculated by 2 methods: mm2 per year and mm per year using the square-root transformation (SQRT) strategy. Simple and multiple linear regression analyses were used to identify the baseline factors associated with the GA progression rate. MAIN OUTCOME MEASURES: Clinical characteristics of GA and the GA progression rate. RESULTS: The mean age was 76.8 ± 8.8 years, and 109 (63.0%) were males. Sixty-two (35.8%) patients had bilateral GA. The mean GA area was 3.06 ± 4.00 mm2 (1.44 ± 1.00 mm [SQRT]). Thirty-eight eyes (22.0%) were classified as having pachychoroid GA. Drusen and reticular pseudodrusen were detected in 115 (66.5%) and 73 (42.2%) eyes, respectively. The mean subfoveal choroidal thickness was 194.7 ± 105.5 µm. In the follow-up group (follow-up period: 46.2 ± 28.9 months), the mean GA progression rate was 1.01 ± 1.09 mm2 per year (0.23 ± 0.18 mm/year [SQRT]). In the multivariable analysis, the baseline GA area (SQRT; P = 0.002) and the presence of reticular pseudodrusen (P < 0.001) were significantly associated with a greater GA progression rate (SQRT). CONCLUSIONS: Certain clinical characteristics of GA in Asian populations may differ from those in White populations. Asian patients with GA showed male dominance and relatively thicker choroid than White patients. There was a group with GA without drusen but with features of pachychoroid. The GA progression rate in this Asian population was relatively lower than that in White populations. Large GA and reticular pseudodrusen were associated with a greater GA progression rate. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cost-Effectiveness Analysis of Ranibizumab Biosimilar for Neovascular Age-Related Macular Degeneration in Japan.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is the world's leading cause of blindness in elderly people. While anti-vascular endothelial growth factor (VEGF) treatments are used as the first option for patients with nAMD, they are generally expensive and need repeated injections. This study aimed to evaluate the cost-effectiveness of anti-VEGF therapies, focusing on the newly launched ranibizumab biosimilar (RBZ BS) in patients with nAMD from a Japanese societal perspective. METHODS: A Markov model was developed to simulate the lifetime transitions of a cohort of treatment-naïve patients with nAMD through health states that were based on the involvement of nAMD (single eye vs. both eyes), the treatment status of the patients, and decimal best-corrected visual acuity. The model compared RBZ BS with branded RBZ, aflibercept (AFL), and AFL as loading dose switched to RBZ BS in maintenance in the treat-and-extend (TAE) regimen (RBZ TAE, AFL TAE, and AFL to RBZ BS TAE, respectively), and with branded RBZ in the pro re nata (PRN) regimen, as well as best supportive care (BSC). All processes were validated by five clinical experts. RESULTS: When TAE regimens were compared, RBZ BS was dominant (higher quality-adjusted life-years (QALYs) and lower total cost) to AFL TAE and AFL to RBZ TAE. The result was robust regardless of whether the clinical data were taken from the direct head-to-head clinical trial or from indirect treatment comparison. RBZ BS TAE was cost-saving compared to RBZ TAE. RBZ BS TAE was estimated to be dominant to BSC owing to a lower societal cost. Like TAE regimens, RBZ BS was cost-saving compared to RBZ PRN and was dominant to BSC in PRN regimens. CONCLUSION: This study suggests that RBZ BS is dominant to other anti-VEGF treatments in patients with nAMD in both TAE and PRN regimens and BSC from a Japanese societal perspective.

Genome-Wide Association Study of Age-Related Macular Degeneration Reveals 2 New Loci Implying Shared Genetic Components with Central Serous Chorioretinopathy.

PURPOSE: To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population. DESIGN: Genome-wide association study (GWAS). PARTICIPANTS: Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses. METHODS: We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants. MAIN OUTCOME MEASURES: Associations of genetic variants with AMD. RESULTS: A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P < 5.0 × 10-8). Of these loci, 4 were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2), and 2 were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all datasets, we observed strong associations in these loci (P = 1.88 × 10-12 and P = 1.35 × 10-9 for meta-analysis for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were associated significantly with CSC (P = 4.86 × 10-3 and P = 4.28 × 10-3 for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (rg [the measure of genetic correlation] = -0.33; P = 0.01; false discovery rate, 0.099). CONCLUSIONS: Our findings imply shared genetic components conferring the risk of both AMD and CSC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Ring formation by Vibrio fusion protein composed of FliF and FliG, MS-ring and C-ring component of bacterial flagellar motor in membrane.

The marine bacterium Vibrio alginolyticus has a single flagellum as a locomotory organ at the cell pole, which is rotated by the Na+-motive force to swim in a liquid. The base of the flagella has a motor composed of a stator and rotor, which serves as a power engine to generate torque through the rotor-stator interaction coupled to Na+ influx through the stator channel. The MS-ring, which is embedded in the membrane at the base of the flagella as part of the rotor, is the initial structure required for flagellum assembly. It comprises 34 molecules of the two-transmembrane protein FliF. FliG, FliM, and FliN form a C-ring just below the MS-ring. FliG is an important rotor protein that interacts with the stator PomA and directly contributes to force generation. We previously found that FliG promotes MS-ring formation in E. coli. In the present study, we constructed a fliF-fliG fusion gene, which encodes an approximately 100 kDa protein, and the successful production of this protein effectively formed the MS-ring in E. coli cells. We observed fuzzy structures around the ring using either electron microscopy or high-speed atomic force microscopy (HS-AFM), suggesting that FliM and FliN are necessary for the formation of a stable ring structure. The HS-AFM movies revealed flexible movements at the FliG region.

16S rRNA nanopore sequencing for the diagnosis of ocular infection: a feasibility study.

OBJECTIVE: We conducted a feasibility study to verify the effectiveness of 16S ribosomal RNA (rRNA) gene analysis using the nanopore sequencer MinION for identifying causative bacteria in several types of ocular infections. METHODS AND ANALYSIS: Four cases of corneal ulcers, one case of endophthalmitis and one case of a conjunctival abscess were included in this study. DNA was extracted from corneal scraping, vitreous samples and secretions from the conjunctival abscess. We conducted 16S rRNA gene amplicon sequencing using MinION and metagenomic DNA analysis. The efficacy of bacterial identification was verified by comparing the conventional culture method with smear observations. RESULTS: 16S rRNA gene sequencing analysis with MinION identified the causative organisms promptly with high accuracy in approximately 4 hours, from ophthalmic specimens. The results of the conventional culture method and 16S rRNA gene sequencing were consistent in all cases. In four of the six cases, a greater variety of organisms was found in the 16S rRNA gene analysis than in bacterial culture. CONCLUSION: Using our workflow, 16S rRNA gene analysis using MinION enabled rapid and accurate identification possible in various kinds of bacterial ocular infections.

Aberrant Corneal Homeostasis in Neurosurgery-Induced Neurotrophic Keratopathy.

The characteristic features of neurotrophic keratopathy have been well documented by in vivo and in vitro studies using animal models. However, case reports of neurotrophic keratopathy induced by neurosurgery are limited. We describe the clinical characteristics, anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) findings of neurotrophic keratopathy induced by surgery for intracranial lesions. This is a case series including 6 eyes of 3 patients (mean age, 69.67 ± 12.50 years) with unilateral neurotrophic keratopathy. The clinical findings of three patients were described and IVCM findings of three patients were analyzed. The duration of neuropathy ranged from 2 to 30 years (median, 22 years). Thickening of the epithelial layer and higher reflection density of the anterior stroma were observed during the healing process using AS-OCT. The mean nerve fiber density of the subepithelial plexus, as determined by IVCM, was 1943 ± 1000 µm/mm2 for neurotrophic eyes and 2242 ± 600.3 µm/mm2 for contralateral eyes (p = 0.0347). The mean respective dendritic cell densities were 30.8 ± 21.8 and 6.25 ± 5.59 cells/mm2 (p < 0.0001), while the mean basal cell sizes were 259 ± 86.5 and 185 ± 45.9 µm2 (p < 0.0001), respectively. These findings suggest that neurosurgery-induced neurotrophic keratopathy may be associated with alterations in the healing process and immune cell distribution in the cornea.

Corneal ulcers with non-infectious appearance caused by nasolacrimal duct obstruction or canaliculitis.

Purpose: To describe the clinical features of corneal ulcers with non-infectious appearance due to nasolacrimal disease in a retrospective case series. Observations: Eight eyes of 8 patients (aged 74.4 ± 11.1 years) with corneal disease due to nasolacrimal duct obstruction or canaliculitis, who were treated between October 2013 and December 2020 at 3 hospitals were included. Patient background, anterior ocular findings, organisms in secretion, and time course during treatment were retrospectively analyzed. The corneal findings were peripheral ulcers (5 cases), phlyctenular keratitis (1 case), and paracentral perforation with slight cellular infiltration (2 cases). All cases were suspected as autoimmune disease-related-corneal ulcers because of the pathogenic region and clinical appearance and later diagnosed as corneal disorders derived from nasolacrimal duct obstruction or canaliculitis. The autoimmune disease-like appearance and purulent secretion connecting the punctum with/without swelling were characteristic. The most common microorganism detected in the purulent secretions was Streptococcus spp.. The resolution of corneal lesions needed steroid eye drops with antibiotic eye drops. Two patients required a superficial corneal transplantation. The extraction of nasolacrimal calculus, punctal tube insertion, or dacryocystorhinostomy was necessary for complete healing of ocular surface disease. Conclusions and importance: Nasolacrimal duct diseases cause corneal disorders without bacterial colonization and growth. When corneal ulcers resemble autoimmune disease in shape and are not accompanied by systemic disease, attention should be paid to nasolacrimal duct obstruction or canaliculitis.

Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in the ALTAIR Study: 96-Week Outcomes in the Polypoidal Choroidal Vasculopathy Subgroup.

INTRODUCTION: To explore the efficacy and safety of intravitreal aflibercept (IVT-AFL) proactive, individualized treat-and-extend (T&E) regimens in exudative age-related macular degeneration (AMD) in the subgroup of patients with polypoidal choroidal vasculopathy (PCV) enrolled in the ALTAIR study. METHODS: This was a PCV subgroup analysis of ALTAIR, a 96-week, randomized, open-label, phase 4 study in treatment-naïve patients with exudative AMD in Japan. Following three initial monthly doses, patients received IVT-AFL at week 16 and were randomized 1:1 to T&E regimens with either 2-week (IVT-AFL-2W) or 4-week (IVT-AFL-4W) adjustments. The primary endpoint of ALTAIR was the mean change in best-corrected visual acuity (BCVA) from baseline to week 52. Endpoints were assessed at weeks 52 and 96. Safety analyses were conducted. RESULTS: A total of 90 patients with PCV were included within the full analysis set. From baseline to week 52, mean [standard deviation (SD)] change in BCVA was + 7.5 (14.7) letters and + 8.2 (11.6) letters in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 96, 91.3% and 90.9% of patients maintained vision in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 52, mean (SD) change in central retinal thickness was - 153 (177) µm and -112 (122) µm in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. Overall, 51.1% of patients (IVT-AFL-2W, 43.5%; IVT-AFL-4W, 59.1%) achieved a treatment interval of 16 weeks between weeks 16 and 96. The safety profile of IVT-AFL was consistent with previous studies. CONCLUSION: In treatment-naïve patients with PCV, IVT-AFL administered using two different T&E regimens improved and maintained functional and anatomic outcomes over 96 weeks while minimizing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02305238.

Successful identification of Granulicatella adiacens in postoperative acute infectious endophthalmitis using a bacterial 16S ribosomal RNA gene-sequencing platform with MinION™: A case report.

Purpose: To evaluate the efficacy of identifying the bacteria by aqueous sampling and vitreous sampling in postoperative infectious endophthalmitis using 16S ribosomal RNA (rRNA) gene analysis with a nanopore sequencer (MinION™). Observation: A 55-year-old woman who underwent cataract surgery at an ophthalmology clinic 18 days ago was referred to our hospital for suspected endophthalmitis. She had light perception visual acuity in her right eye; however, the eye was severely inflamed, with a hypopyon and a fibrinous membrane in the anterior chamber. The fundus was not visible because of vitreous opacity on a B-scan image. Based on the diagnosis of postoperative acute infectious endophthalmitis, we performed a vitrectomy, intraocular lens extraction, and silicone oil tamponade. On postoperative day 14, the inflammation resolved. An aqueous sample was collected before surgical treatment, and the vitreous sample was collected during the operation. Both samples underwent 16S rRNA gene analysis with a nanopore sequencer MinION™ to identify the causative organism. Conclusions and Importance: In the aqueous humor, Granulicatella adiacens and Cutibacterium acnes were identified before the operation, while only Granulicatella adiacens was detected in the vitreous sample after the operation. Although the aqueous humor sample might contain commensal bacteria, it could provide a predictable result before the operation. It can also provide a substitute for a vitreous sample to allow earlier identification of the causative organism.

Effectiveness of Current Treatments for Wet Age-Related Macular Degeneration in Japan: A Systematic Review and Pooled Data Analysis.

PURPOSE: We conducted a systematic review to investigate the effectiveness of clinical treatments for wet age-related macular degeneration (wAMD) in Japanese patients in the decade since anti-vascular endothelial growth factor (VEGF) therapies were introduced. METHODS: PubMed was searched for articles published in English between 1 January 2008 and 30 September 2018 using a multistring search strategy. Reviews were scanned for additional relevant studies and select gray literature was evaluated. Mean and/or median for the logarithm of the minimum angle of resolution (logMAR) visual acuity (VA), central retinal thickness (CRT), and the number of injections after 12 months of treatment were calculated using extracted data. Data were stratified by disease type and treatment modality. RESULTS: Of 335 studies identified, 94 were selected for data extraction (147 treatment arms; typical AMD, n = 25; polypoidal choroidal vasculopathy [PCV], n = 85). Mean (median) logMAR VA was 0.44 (0.32) for typical AMD and 0.34 (0.31) for PCV; the respective mean number of anti-VEGF injections was 5.6 and 4.6. The mean CRT was approximately 220 µm for both groups. For typical AMD, anti-VEGF monotherapy resulted in better VA outcomes than photodynamic therapy (PDT) alone. For PCV, anti-VEGF monotherapy or anti-VEGF plus PDT combination therapy resulted in better VA and CRT outcomes than PDT monotherapy. Combination therapy required fewer injections than anti-VEGF monotherapy (PCV, 3.2 versus 5.3). CONCLUSION: wAMD treatment has advanced dramatically in the years since anti-VEGF drugs were introduced in Japan. Discrete patient populations may benefit from differing management regimens, including the fewer injections required with combination therapy.

Interim Results of Post-Marketing Observational Study of Omidenepag Isopropyl for Glaucoma and Ocular Hypertension in Japan.

INTRODUCTION: This post-marketing observational interim analysis evaluated the 12-month effectiveness and safety of omidenepag isopropyl (OMDI) ophthalmic solution in daily clinical settings. METHODS: This was a multicenter, large-scale, non-interventional, prospective, observational study conducted in Japan. The target enrollment was 3900 patients, and the overall observation period was 12 months. Patients with glaucoma and ocular hypertension (OH) with no previous history of OMDI use were enrolled. The key endpoints were change in intraocular pressure (IOP) from baseline and the incidence of adverse reactions (ADRs). RESULTS: A total of 1862 patients were evaluated in this 12-month interim analysis. Most patients were diagnosed with normal-tension glaucoma (NTG, 62.0%). The treatment patterns with OMDI were naïve monotherapy (48.4%), switching monotherapy (18.4%), and concomitant therapy (31.1%). The overall incidence of ADRs was 24.3%, which was similar between the monotherapy and concomitant therapy groups. Common ADRs were conjunctival hyperemia, refractive disorder, and myopia. Macular edema was observed in four patients. No ADRs categorized as prostaglandin-associated periorbitopathy were observed. There was a significant reduction in mean IOP at 12 months, with a change of - 1.9 ± 2.9 mmHg from baseline (reduction - 10.4 ± 16.5%). The mean IOP change from baseline was - 2.7 ± 2.6 mmHg in the naïve monotherapy group, - 1.1 ± 2.6 mmHg in the switching monotherapy group, and - 1.6 ± 3.1 mmHg in the concomitant therapy group (all P < 0.05). The mean IOP decreased by - 2.5 ± 3.2 mmHg, - 1.5 ± 2.4 mmHg, and - 2.3 ± 4.5 mmHg in the primary open-angle glaucoma (POAG), NTG, and OH groups, respectively. The treatment persistence with OMDI was 82.4%. CONCLUSION: This study demonstrated the safety and efficacy of OMDI for glaucoma and OH as monotherapy and concomitant therapy in daily clinical settings. In this interim analysis, OMDI showed a favorable benefit-risk profile, and can be first-line therapy for glaucoma.

Efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy in Japanese participants of HAWK.

PURPOSE: To compare the efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy (PCV) over 96 weeks in the HAWK study. DESIGN: HAWK was a global, 2-year, randomised, double-masked, multicentre phase III trial in participants with neovascular age-related macular degeneration. METHODS: Of the Japanese participants with PCV, 39 received brolucizumab 6 mg and 30 received aflibercept 2 mg. After 3 monthly loading doses, brolucizumab-treated eyes received an injection every 12 weeks (q12w) but were adjusted to q8w if disease activity was detected. Aflibercept-treated eyes received fixed q8w dosing. Mean change in best-corrected visual acuity (BCVA), the proportion of participants on q12w, retinal thickness, retinal fluid changes and safety were assessed to Week 96. RESULTS: Mean change in BCVA (early treatment diabetic retinopathy study (ETDRS) letters) from baseline to week 48/week 96 was+10.4/+11.4 for brolucizumab and +11.6/+11.1 for aflibercept. For brolucizumab-treated eyes, the probability of only q12w dosing after loading through week 48 was 76%, and 68% through week 96. Fluid resolution was greater with brolucizumab than aflibercept: respective proportions of eyes with intraretinal fluid and/or subretinal fluid were 7.7% and 30% at week 48% and 12.8% and 16.7% at week 96. Brolucizumab exhibited an overall well-tolerated safety profile despite a higher rate of intraocular inflammation compared with aflibercept. CONCLUSION: In Japanese eyes with PCV, brolucizumab q12w/q8w monotherapy resulted in robust and consistent BCVA gains that were comparable to q8w aflibercept dosing. Anatomical outcomes favoured brolucizumab over aflibercept, with 76% of brolucizumab participants maintained on q12w dosing after loading to week 48.

Dry age-related macular degeneration in the Japanese population.

PURPOSE: To elucidate the clinical characteristics of eyes with dry age-related macular degeneration (AMD) in Japan. STUDY DESIGN: Retrospective. METHODS: We performed a nationwide survey of dry AMD. A questionnaire on dry AMD was sent to 3,801 major hospitals and eye clinics nationwide. Whenever both eyes met the diagnostic criteria, only the eye with more advanced geographic atrophy was included. RESULTS: In the current survey, 81 patients (81 eyes) with dry AMD were included. Of the 81 patients, 56 (69.1%) were men, and the mean age of the patients was 76.6 ± 8.4 (range, 54-94) years. Twenty-four patients (29.6%) had a history of smoking. The decimal best corrected-visual acuity (BCVA) was equal to or better than 0.7 in 25 eyes (30.9%), but worse than 0.1 in 17 eyes (21.0%). The mean BCVA was 0.62 ± 0.59 in logarithm of the minimum angle of resolution. Lesion size (the greatest linear dimension of the largest geographic atrophy) was ≥ 2 disc diameter in 33 eyes (40.7%) and < 1 disc diameter in 21 eyes (25.9%). Soft drusen was observed in 27 eyes (33.3%), and reticular pseudodrusen was observed in 31 eyes (38.3%). Of the 81 patients, the other eye was diagnosed as dry AMD in 26 eyes (32.1%), neovascular AMD in 16 eyes (19.8%), and intermediate AMD in 18 eyes (22.2%). CONCLUSION: Dry AMD in the Japanese population has characteristics of male predominance, older age, high prevalence of reticular pseudodrusen, and high bilaterality.

Synthetic rubber sheet to manage exposure keratopathy.

PURPOSE: Exposure keratopathy often progresses even with conventional various treatments and needs plastic surgery. However, plastic surgery of eye lid is often difficult in cases with poor general condition by cerebrovascular disorders. We will propose a novel method using synthetic rubber sheet to manage the exposure keratopathy under poor general conditions. OBSERVATIONS: We treated with synthetic rubber sheet on 9 eyes of 9 patients who suffered from refractory exposure keratopathy due to cerebrovascular disorders. Sheets cut from sterile surgical gloves made of synthetic rubber (SR sheets) were placed directly onto the ocular surface with antibiotic ointment and fixed with gauze and tape. Severity of the exposure keratopathy was scored before and after the application of SR sheet. Covered ocular surface with SR sheet could keep an adequate moist environment and exposure keratopathy was improved in all the cases with no adverse effects during an average observation period of 166.2 days. CONCLUSIONS AND IMPORTANCE: Sterile synthetic rubber sheet cut from surgical gloves is an effective, safe, easy, and economical material to maintain better condition of ocular surface and especially useful for refractory exposure keratopathy under poor general condition.