Cost-effectiveness Analysis of Ranibizumab Biosimilar for Neovascular Age-Related Macular Degeneration and its Subtypes from the Societal and Patient Perspectives in Japan.

INTRODUCTION: This study evaluated the cost-effectiveness of anti-vascular endothelial growth factor (VEGF) therapies for subtypes of neovascular age-related macular degeneration (nAMD) from the societal perspective, and for any nAMD from the patient perspective in Japan. METHODS: A Markov model was developed to simulate the lifetime transitions of a cohort of patients with nAMD through various health states based on the involvement of nAMD, the treatment status, and decimal best-corrected visual acuity. Ranibizumab biosimilar was compared with aflibercept from the societal perspective regardless of treatment regimen for the analysis of three subtypes (typical nAMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP)). Two analyses from the patient perspective focusing on the treat-and-extend regimens were performed, one with a cap on patients' copayments and one without. Ranibizumab biosimilar was compared with branded ranibizumab, aflibercept, aflibercept as the loading dose switching to ranibizumab biosimilar during maintenance (aflibercept switching to ranibizumab biosimilar), and best supportive care (BSC), for patients with any nAMD. RESULTS: In the subtype analyses, ranibizumab biosimilar when compared with aflibercept resulted in incremental quality-adjusted life years (QALYs) of - 0.015, 0.026, and 0.009, and the incremental costs of Japanese yen (JPY) - 50,447, JPY - 997,243, and JPY - 1,286,570 for typical nAMD, PCV, and RAP, respectively. From the patient perspective, ranibizumab biosimilar had incremental QALYs of 0.015, 0.009, and 0.307, compared with aflibercept, aflibercept switching to ranibizumab biosimilar, and BSC, respectively. The incremental costs for ranibizumab biosimilar over a patient lifetime excluding the cap on copayment were estimated to be JPY - 138,948, JPY - 391,935, JPY - 209,099, and JPY - 6,377,345, compared with branded ranibizumab, aflibercept, aflibercept switching to ranibizumab biosimilar, and BSC, respectively. CONCLUSIONS: Ranibizumab biosimilar was demonstrated as a cost-saving option compared to aflibercept across all subtypes of nAMD, irrespective of the perspectives considered.

Evaluating photodynamic therapy versus brolucizumab as a second-line treatment for polypoidal choroidal vasculopathy.

BACKGROUND: To compare the one-year outcomes between intravitreal brolucizumab (IVBr) monotherapy and photodynamic therapy (PDT) as a second-line treatment in patients with polypoidal choroidal vasculopathy (PCV) who did not respond to first-line therapy. METHODS: This case-control study included eyes with PCV that do not respond to aflibercept or ranibizumab. The patients were retrospectively registered. We compared outcomes, including best-corrected visual acuity (BCVA), anatomical results, and the need for additional treatments, between IVBr and a combination therapy using PDT as second-line treatments for refractory PCV, after adjusting for potential confounders. We analyzed E-values to evaluate the robustness of the results against unmeasured confounders. RESULTS: Twenty-two eyes received IVBr, and twenty-four underwent PDT. No apparent differences were observed in BCVA and central macular thickness (CMT) changes from baseline between the groups (IVBr vs. PDT: BCVA, 0.01 ± 0.47 logMAR vs. 0.04 ± 0.18 logMAR, P-value = 0.756; CMT: - 36.3 ± 99.4 µm vs. - 114.7 ± 181.4 µm, P-value = 0.146). Only in the PDT group, five eyes (20.8%) did not require additional treatment after the second-line treatment, the adjusted odds ratio indicating no further treatment needed was 11.98 (95% confidence interval: 1.42-2070.07, P-value = 0.019). The E-value for the adjusted odds ratio was 23.44. CONCLUSIONS: Both second-line treatments for PCV exhibited similar visual and anatomical outcomes. Only in the PDT-treated eyes were there some patients who did not require further treatment after second-line therapy.

Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial.

BACKGROUND: A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO. METHODS: PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503). FINDINGS: Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was -0·57 letters (95% CI -2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and -1·44 letters (-3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%]). INTERPRETATION: Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO. FUNDING: Regeneron Pharmaceuticals and Bayer.

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.

Efficacy and Safety of Faricimab for Macular Edema due to Retinal Vein Occlusion: 24-Week Results from the BALATON and COMINO Trials.

PURPOSE: To evaluate the 24-week efficacy and safety of the dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A inhibitor faricimab versus aflibercept in patients with vein occlusion. DESIGN: Phase 3, global, randomized, double-masked, active comparator-controlled trials: BALATON/COMINO (ClincalTrials.gov identifiers: NCT04740905/NCT04740931; sites: 149/192). PARTICIPANTS: Patients with treatment-naïve foveal center-involved macular edema resulting from branch (BALATON) or central or hemiretinal (COMINO) RVO. METHODS: Patients were randomized 1:1 to faricimab 6.0 mg or aflibercept 2.0 mg every 4 weeks for 24 weeks. MAIN OUTCOME MEASURES: Primary end point: change in best-corrected visual acuity (BCVA) from baseline to week 24. Efficacy analyses included patients in the intention-to-treat population. Safety analyses included patients who received ≥ 1 doses of study drug. RESULTS: Enrollment: BALATON, n = 553; COMINO, n = 729. The BCVA gains from the baseline to week 24 with faricimab were noninferior versus aflibercept in BALATON (adjusted mean change, +16.9 letters [95.03% confidence interval (CI), 15.7-18.1 letters] vs. +17.5 letters [95.03% CI, 16.3-18.6 letters]) and COMINO (+16.9 letters [95.03% CI, 15.4-18.3 letters] vs. +17.3 letters [95.03% CI, 15.9-18.8 letters]). Adjusted mean central subfield thickness reductions from the baseline were comparable for faricimab and aflibercept at week 24 in BALATON (-311.4 µm [95.03% CI, -316.4 to -306.4 µm] and -304.4 µm [95.03% CI, -309.3 to -299.4 µm]) and COMINO (-461.6 µm [95.03% CI, -471.4 to -451.9 µm] and -448.8 µm [95.03% CI, -458.6 to -439.0 µm]). A greater proportion of patients in the faricimab versus aflibercept arm achieved absence of fluorescein angiography-based macular leakage at week 24 in BALATON (33.6% vs. 21.0%; nominal P = 0.0023) and COMINO (44.4% vs. 30.0%; nominal P = 0.0002). Faricimab was well tolerated, with an acceptable safety profile comparable with aflibercept. The incidence of ocular adverse events was similar between patients receiving faricimab (16.3% [n = 45] and 23.0% [n = 84] in BALATON and COMINO, respectively) and aflibercept (20.4% [n = 56] and 27.7% [n = 100], respectively). CONCLUSIONS: These findings demonstrate the efficacy and safety of faricimab, a dual Ang-2/VEGF-A inhibitor, in patients with macular edema secondary to retinal vein occlusion. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy, Durability, and Safety of Faricimab in Patients From Asian Countries With Diabetic Macular Edema: 1-Year Subgroup Analysis of the Phase III YOSEMITE and RHINE Trials.

PURPOSE: To assess the 1-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema from Asian and non-Asian countries. DESIGN: Global, multicenter, randomized, double-masked, active comparator-controlled, phase III trials. METHODS: Subgroup analysis of patients from Asian (N=144) and non-Asian (N=1747) countries randomized to faricimab 6.0 mg every 8 weeks (Q8W), faricimab per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W in the YOSEMITE/RHINE (NCT03622580/NCT03622593) trials. Primary endpoint: best-corrected visual acuity (BCVA) changes from baseline at 1 year, averaged over weeks 48, 52, and 56. RESULTS: Mean BCVA change from baseline at 1 year in the Asian country subgroup was similar between arms: faricimab Q8W (n=50), +10.9 (95% CI: 8.6-13.2); faricimab PTI (n=48) +10.0 (7.7-12.4) letters; aflibercept Q8W (n=46) +9.0 (6.6-11.4) letters. BCVA gains in the non-Asian country subgroup (n=582, 584, 581) were +11.3 (10.5-12.1), +11.2 (10.5-12.0), and +10.7 (9.9-11.5) letters, respectively. At 1 year, 49% of Asian country patients in the faricimab PTI arm achieved Q16W dosing (vs. 52% non-Asian) and 78% achieved ≥Q12W dosing (vs. 72% non-Asian). Anatomic improvementswere generally greater with faricimab versus aflibercept and similar between the Asian and non-Asian country subgroups. Faricimab was well tolerated, with no new safety signals. CONCLUSIONS: Vision, durability, anatomic, and safety outcomes were generally similar between the Asian and non-Asian country subgroups, suggesting that global YOSEMITE/RHINE results may be generalized to the Asian population. These data support the benefit-risk profile of faricimab for treating Asian patients with diabetic macular edema.

Anti-VEGF Treatment Strategies for 3 Subtypes of Neovascular Age-Related Macular Degeneration in a Clinical Setting: A Multicenter Cohort Study in Japan.

PURPOSE: Neovascular age-related macular degeneration (nAMD) is classified into typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). This study investigated clinical features of the 3 subtypes and visual outcome associated with treatment regimens in a large cohort of patients with nAMD in a clinical setting. DESIGN: Retrospective multicenter cohort study. PARTICIPANTS: Five hundred patients with treatment-naive nAMD (268 tAMD, 200 PCV, and 32 RAP) initiated with anti-VEGF agents and followed for 1 year. METHODS: Medical records were reviewed to extract demographic data, best-corrected visual acuity at baseline and 1 year after treatment initiation, spectral-domain OCT findings, baseline fellow eye condition, systemic factors, treatment strategies, and number of intravitreal injections in the first year. MAIN OUTCOME MEASURES: Primary outcome measures were anti-VEGF treatment strategy (ranibizumab or aflibercept, anti-VEGF regimen, concomitant photodynamic therapy, drug switch), best-corrected visual acuity at 1 year, and factors associated with visual acuity. RESULTS: Patients with RAP were significantly older, were more commonly women, and had more macular lesions in fellow eye than patients with tAMD and PCV. Smoking history and diabetes prevalence were not different among the 3 subtypes. Frequencies of subretinal fluid were higher and intraretinal fluid were lower in tAMD and PCV than in RAP, whereas serous pigment epithelial detachment and subretinal hemorrhage were higher in PCV than in tAMD and RAP. Choice of anti-VEGF agents and treatment regimens did not differ among 3 subtypes. The aflibercept-to-ranibizumab ratio was approximately 7:3. The mean number of injections in 1 year was 5.3 ± 2.4 in nAMD overall, which was significantly less in pro re nata (PRN) than in treat and extend (TAE) regardless of the anti-VEGF agent. Best-corrected visual acuity improved in all 3 subtypes, although it was not significant in patients with RAP. CONCLUSIONS: This clinical study demonstrates that treatment regimens were similar in 3 subtypes and aflibercept was used in 70% of all patients. Approximately 5 injections were given in the first year regardless of the anti-VEGF agent, which was significantly less in PRN regimen than in TAE. Visual acuity improvement was observed after 1-year anti-VEGF therapy in all 3 subtypes, but was not significant in RAP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effects of Perfluorocarbon Use during Rhegmatogenous Retinal Detachment Surgery on Postoperative Outcomes.

INTRODUCTION: The aim of this study was to determine whether the use of perfluorocarbon liquid (PFCL) affects the rate of retinal re-attachments after an initial attachment by vitrectomy in eyes with rhegmatogenous retinal detachment (RRD). METHODS: This was a retrospective, observational, multicenter study of 3,446 eyes registered in the Japanese vitreoretinal surgery treatment information database. Of these, 2,648 eyes had undergone vitrectomy as the first surgery for RRD. The re-attachment rates after the primary vitrectomy with or without PFCL were evaluated. In addition, the significance of factors affecting the re-detachments was determined by univariate and multivariate analyses. The measured outcomes were the rates of re-attachments after the primary vitrectomy with or without the use of PFCL. RESULTS: A total of 2,362 eyes in the database were analyzed: 325 had and 2,037 did not have PFCL injected into the vitreous cavity during the vitrectomy. The rate of re-attachments was 91.5% in the PFCL group and 93.2% in the non-PFCL group (p = 0.46, χ2 test). Although there were several risk factors associated with the re-detachments in eyes without PFCL (p < 0.05, Welch's t tests, and Fisher's exact tests), they were not associated in eyes with PFCL use. However, multivariate analyses showed that there was no significant association between the use and the non-use of PFCL in the rate of re-detachments (ß = -0.08, p = 0.46). CONCLUSIONS: The use of PFCL during the initial vitrectomy for RRD does not affect the rate of re-attachments.

VEGF-A165 is the predominant VEGF-A isoform in platelets, while VEGF-A121 is abundant in serum and plasma from healthy individuals.

Vascular endothelial growth factor A (VEGF-A) plays pivotal roles in regulating tumor angiogenesis as well as physiological vascular function. The major VEGF-A isoforms, VEGF-A121 and VEGF-A165, in serum, plasma, and platelets have not been exactly evaluated due to the lack of the appropriate assay system. Antibodies against human VEGF-A121 and VEGF-A165 (hVEGF-A121 and hVEGF-A165) were successfully produced and Enzyme-Linked ImmunoSorbent Assay (ELISA) for hVEGF-A121 and hVEGF-A165 were separately created by these monoclonal antibodies. The measurement of recombinant hVEGF-A121 and hVEGF-A165 by the created ELISA showed no cross-reaction between hVEGF-A121 and hVEGF-A165 in conditioned media from HEK293 cells transfected with either hVEGF-A121 or hVEGF-A165 expression vector. The levels of VEGF-A121 and VEGF-A165 in serum, plasma, and platelets from 59 healthy volunteers proved that VEGF-A121 level was higher than VEGF-A165 in both plasma and serum in all the cases. VEGF-A121 or VEGF-A165 in serum represented higher level than that in plasma. In contrast, the level of VEGF-A165 was higher than VEGF-A121 in platelets. The newly developed ELISAs for hVEGF-A121 and hVEGF-A165 revealed different ratios of VEGF isoforms in serum, plasma, and platelets. Measuring these isoforms in combination provides useful information as biomarkers for diseases involving VEGF-A121 and VEGF-A165.

International Validation of Myopic Traction Maculopathy Staging System.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the interobserver agreement of the myopic traction maculopathy (MTM) staging system (MSS). PATIENTS AND METHODS: Each observer was asked to look at the MSS Table and then identify, in each optical coherence tomography scan, one among four stages of MTM in the retina, one among three stages in the fovea, and, as secondary findings, the presence or absence of an outer lamellar macular hole and the presence or absence of epiretinal abnormalities. The interobserver agreement value was calculated using the Gwet's AC1 unweighted and AC2 weighted statistics. The outcomes were interpreted as poor (<0.00), slight (0.00 to 0.20), fair (0.21 to 0.40), moderate (0.41 to 0.60), substantial (0.61 to 0.80), or almost perfect (0.81 to 1.00) agreement. RESULTS: The agreement, among 65 participants, was 0.62 (AC1) and 0.77 (AC2) for the retina stage; 0.63 (AC1) and 0.81 (AC2) for the fovea stage; 0.56 (AC1) for the outer lamellar macular hole; and 0.26 (AC1) for epiretinal abnormalities. CONCLUSION: The MSS is highly reproducible and helps ophthalmologists to share information on MTM in a more accurate and reliable way. [Ophthalmic Surg Lasers Imaging Retina 2023;54(3):153-157.].

Simultaneous Occurrence of Buckle Infection and Migration: A Case Report.

Background: When scleral buckling is performed using a #240 encircling band anterior to the equator for rhegmatogenous retinal detachment, buckle migration may occur anteriorly, eroding the rectus muscle. There are few cases of buckle migration occurring simultaneously with buckle infection. Notably, most previous reports included inadequate data on the pathophysiology of buckle migration and did not include the Hess test and perioperative images. Case presentation: A 36-year-old man with a history of atopic dermatitis underwent scleral buckling for rhegmatogenous retinal detachment of the left eye with #287 and #240 encircling bands at Kagoshima University Hospital. Four years later, he developed discharge, redness, and diplopia of the left eye. He was then referred to our hospital because buckle infection was suspected. The buckle was partially visible on the lower nasal side. Optical coherence tomography of the anterior chamber revealed the buckle to be on the nasal side and overlying the medial rectus muscle. Buckle migration and infection in the left eye was diagnosed, and early buckle removal was recommended. Two weeks later, on the day before surgery, conjunctival melting progressed in the nasal and inferior areas, and the buckle was exposed to a greater extent. In the surgical video at the initial surgery, the silicone band was confirmed to pass under the four rectus muscles, specifically the inferior and medial rectus muscles. At the beginning of the second surgery, we confirmed that the buckles were over the inferior and medial rectus muscles. As far as could be observed after buckle removal, the inferior and medial rectus muscles were not present at the normal location. Postoperatively, ocular pain and discharge quickly resolved. The subjective symptoms of diplopia also improved, and the postoperative Hess chart showed an improved ocular movement in the upward and lateral directions. Conclusions: Buckle migration is a rare postoperative complication of scleral buckling; however, patients at risk of buckle migration, such as those with encircling scleral buckle anterior to the eyeball, should be monitored with caution. If a buckle infection develops, buckle migration may occur within a short period, and early buckle removal should be considered.

Changes in choriocapillaris structure occurring in idiopathic macular hole before and after vitrectomy.

PURPOSE: The aim of this study was to analyze the anatomical choroidal vascular layers and the changes in idiopathic macular hole (IMH) eyes over time after vitrectomy. METHODS: This is a retrospective observational case-control study. Fifteen eyes from 15 patients who received vitrectomy for IMH and age-matched 15 eyes from 15 healthy controls were enrolled in this study. Retinal and choroidal structures were quantitatively analyzed before vitrectomy and 1 and 2 months after surgery using spectral domain-optical coherence tomography. Each choroidal vascular layer was divided into the choriocapillaris, Sattler's layer, and Haller's layer, and then, the choroidal area (CA), luminal area (LA), stromal area (SA), and central choroidal thickness (CCT) were calculated using binarization techniques. The ratio of LA to CA was defined as the L/C ratio. RESULTS: The CA, LA, and L/C ratios were 36.9 ± 6.2, 23.4 ± 5.0, and 63.1 ± 7.2 in the choriocapillaris of IMH and were 47.3 ± 6.6, 38.3 ± 5.6, and 80.9 ± 4.1 in that of control eyes, respectively. Those values were significantly lower in IMH eyes than in control eyes (each P < 0.01), whereas there was no significant difference in total choroid, Sattler's layer, and Haller's layer or CCT. The ellipsoid zone defect length showed a significant negative correlation with the L/C ratio in total choroid and with CA and LA in the choriocapillaris of IMH (R = - 0.61, P < 0.05, R = - 0.77, P < 0.01, and R = - 0.71, P < 0.01, respectively). In the choriocapillaris, the LA were 23.4 ± 5.0, 27.7 ± 3.8, and 30.9 ± 4.4, and the L/C ratios were 63.1 ± 7.2, 74.3 ± 6.4, and 76.6 ± 5.4 at baseline, 1 month, and 2 months after vitrectomy, respectively. Those values showed a significant increase over time after surgery (each P < 0.05), whereas the other choroidal layers did not alter consistently with respect to changes in choroidal structure. CONCLUSIONS: The current OCT-based study demonstrated that the choriocapillaris was exclusively disrupted between choroidal vascular structures in IMH, which may correlate with the ellipsoid zone defect. Furthermore, the L/C ratio of choriocapillaris recovered after IMH repair, suggesting an improved balance between supply and demand of oxygen that has collapsed due to temporary loss of central retinal function by IMH.

FULL-THICKNESS MACULAR HOLE WITH PERSISTENT BROAD VITREOMACULAR ATTACHMENT: Clinical Characteristics and Surgical Outcomes.

PURPOSE: To describe the characteristics and surgical outcomes of full-thickness macular holes (FTMHs) with persistent broad vitreomacular attachment. METHODS: This was a retrospective, observational case series. Consecutive patients undergoing pars plana vitrectomy for FTMHs with persistent broad vitreomacular attachment (study group) were reviewed. Clinical charts, optical coherence tomography (OCT) features of macular holes, and surgical outcomes were reviewed and compared with those with typical FTMH with focal vitreomacular traction (control group). RESULTS: A total of 15 eyes of 14 consecutive patients (eight males and six females with a mean age of 60.6 years) were included in the study group. OCT showed a zone of at least 1,500 µm all around the circumference of the fovea where the vitreous was attached. On OCT, epiretinal membrane and epiretinal proliferation were observed in 73% and 87% of cases, respectively. Compared with the control group, the study group was younger (P = 0.027) and had better preoperative visual acuity (P = 0.007). All FTMHs closed after one surgery in both groups, and the postoperative visual acuity of the study group was better than that of the control group (P = 0.002). CONCLUSION: Full-thickness macular holes may have developed under the condition that the vitreous cortex was broadly attached around the hole. These FTMHs were associated with younger age, better baseline visual acuity, and a higher incidence of epiretinal membranes and epiretinal proliferations compared with macular hole with focal vitreomacular traction. The surgical outcome was favorable, but the pathogenesis of FTMH development remains unclear.

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.

Increased incidence of endophthalmitis after vitrectomy relative to face mask wearing during COVID-19 pandemic.

BACKGROUND/AIMS: To determine the incidence and causative pathogens of endophthalmitis after vitrectomy during strict face mask wearing in the COVID-19 period. METHODS: This was a retrospective multicentre study including 31 ophthalmological institutions of the Japanese Retina and Vitreous Society or Japan-Clinical Retina Study group. Patients who had undergone vitrectomy during 2019, the pre-COVID-19 period, and from July 2020 to June 2021, the COVID-mask period, were studied. The results of cataract surgery were used as a control. The total number of vitrectomies and the total number of postoperative endophthalmitis were determined. Then, the differences in the incidence of postoperative endophthalmitis between the pre-COVID-19 period and the COVID-mask period, and the type of pathogens causing the endophthalmitis were studied. RESULTS: The incidence of postvitrectomy endophthalmitis was significantly lower in the pre-COVID-19 period with 16 568 surgeries and 18 endophthalmitis cases (0.11%) than in the COVID-mask period of 14 929 surgeries and 31 endophthalmitis cases (0.21%; p=0.031, OR=1.913, 95% CI 1.078 to 3.394). In the pre-COVID-19 period, 4 of the 18 eyes were culture positive, and all were of the Staphylococcus family. In the COVID-mask period, 9 of the 31 eyes were culture positive, and 4 cases were related to oral commensals including Streptococcus spp, which are reportedly very rare in endophthalmitis after vitrectomy. CONCLUSIONS: It is necessary for physicians to be aware of the higher incidence of postvitrectomy endophthalmitis during the COVID-mask period, and to treat their patients appropriately.

Japan Ocular Imaging Registry: a national ophthalmology real-world database.

In 2017, the Japanese Ophthalmological Society (JOS) created the Japan Ocular Imaging (JOI) registry, a national database of images and clinical data in the field of ophthalmology in Japan. The JOI registry automatically transfers the information stored in the electronic medical records of each institution to the cloud storage governed by the JOS. This process adheres to Japanese laws and regulations such as the Act on the Protection of Personal Information and the relevant laws of Japan, the Ethical Guidelines for Medical and Biological Research Involving Human Subjects, and the Medical Information System Security Management Guideline of Japan. The JOI registry works closely with academia in ophthalmology, as well as the Japan Association for Medical Informatics, the Japan Ophthalmic Instrument Association, and manufacturers of ophthalmic medical devices. The collected data will be used in studies and surveys to improve the quality of ophthalmic care. The JOI registry has been created as a common asset for the entire ophthalmology field, and welcomes participation of related institutions to utilize the infrastructure to promote multicenter joint research and development. The JOI registry network intends to cover all ophthalmological facilities, including clinics. However, the project is currently being conducted with the cooperation of 22 university hospitals, one private hospital, and two health checkup facilities. As of October 2021, six facilities are connected to the JOI registry network; it comprises a total of 486,189 fundus images, 25,224 optical coherence tomography images, and 11,565 visual field results, among others, are stored in the JOI registry. This project was initially funded by a national funding agency, the Japan Agency for Medical Research and Development (AMED) (ICT Infrastructure Establishment and Implementation of Artificial Intelligence for Clinical and Medical Research, 2017-2019). The General Incorporated Association Japan Ocular Imaging Registry was established in 2019, following which the association is managing the JOI registry under the governance of the JOS. The JOI registry is aiming to become a large-scale real-world database comparable to the Intelligent Research in Sight registry of the United States.

Differences in clinical characteristics and treatment outcomes of submacular hemorrhage caused by age-related macular degeneration and retinal macroaneurysms: A multicenter survey from the Japan Clinical Retina Study (J-CREST) group.

PURPOSE: To evaluate the clinical characteristics, treatment trends, and visual prognosis of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD) and retinal arterial macroaneurysm (RAM). METHODS: This retrospective study enrolled 187 Japanese patients with SMH at 10 institutions from 2015 to 2018. Medical records including SMH etiology, best-corrected visual acuity (BCVA), fundus photographs, optical coherence tomography images, and selected treatments were analyzed. RESULTS: Major causes of SMH were typical nAMD (tnAMD) (18%), polypoidal choroidal vasculopathy (PCV) (50%) and RAM (29%). Age, male/female ratio, baseline BCVA, central retinal thickness, and involved retinal layers were significantly different between etiologies (all P<0.0001). Treatment with anti-vascular endothelial growth factor drugs with and without intravitreal gas injection was chosen for half of eyes in the tnAMD and PCV groups, whereas vitrectomy was performed in 83.7% of eyes with RAM. The final BCVA improved significantly from baseline in the PCV and RAM groups (P = 0.0009, P<0.0001) and final BCVA was significantly better in the PCV group at a level similar to the other groups (P = 0.0007, P = 0.0008). BCVA improvement from baseline was significantly greater in the RAM group compared with the tnAMD (P = 0.0152) and PCV (P = 0.017) groups. Multivariate analysis revealed better final BCVA was significantly associated with younger age (P = 0.0054), better baseline BCVA (P = 0.0021), RAM subtype (P = 0.0446), and no tnAMD (P = 0.001). CONCLUSIONS: The characteristics of, and treatment strategy for, SMH were different between the underlying diseases. Anti-vascular endothelial growth factor treatment with or without expansile gas was mainly chosen for SMH in tnAMD and PCV, whereas vitrectomy with gas was the most common treatment for RAM, and the higher rate for vitrectomy might result in the greater BCVA improvement in the RAM group than in the other groups. Final BCVA was better in PCV, RAM, and tnAMD, in that order, because patients with PCV were younger and had better baseline BCVA.

OCULAR FACTORS RELATED TO PREOPERATIVE ENLARGEMENT OF IDIOPATHIC MACULAR HOLE DIAMETER.

PURPOSE: To determine the preoperative factors that are significantly correlated with an enlargement of an idiopathic macular hole (MH) during the one-month preoperative period. METHODS: This was a retrospective cross-sectional study of patients with MH who had undergone vitrectomy in the Kagoshima University Hospital. The stage of the MH was determined by using spectral domain optical coherence tomography. Patients who had optical coherence tomography images at two time points more than 14 days apart before the vitrectomy were studied. RESULTS: The MH participants were at Stage 2 in 44 eyes, at Stage 3 in 58 eyes, and at Stage 4 in 38 eyes. The rate of increase of the hole diameter was 26.0 ± 42.3% at Stage 2, 5.52 ± 15.5% at Stage 3, and 8.04 ± 18.7% at Stage 4. The rate of change at Stage 2 was significantly greater than that at Stage 3 and Stage 4 (both P < 0.01). In Stage 2, the MH diameter at the initial visit was significantly and negatively correlated with the rate of MH enlargement (r = -0.35, P = 0.021). CONCLUSION: Patients with Stage 2 MHs, especially eyes with small hole diameter, should be considered for early surgery.

Visual prognosis of submacular hemorrhage secondary to age-related macular degeneration: A retrospective multicenter survey.

PURPOSE: To investigate the clinical features, treatment options, and visual outcomes of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD). DESIGN: A retrospective, observational case series. METHODS: Setting: Multicenter institutional setting. Patient Population: A total of 127 patients (127 eyes; 88 men, 39 women; (mean age, 74.2 years)) diagnosed with AMD-associated SMHs exceeding 2 disc diameters involving the fovea. Observation: The AMD types, previous treatments, treatment options, anatomic findings, and best-corrected visual acuity (BCVA) were assessed. Main Outcome Measures: Clinical features, treatment options, and visual outcomes of SMHs secondary to nAMD. RESULTS: Thirty-two eyes had typical AMD, 94 eyes polypoidal choroidal vasculopathy (PCV), and one eye retinal angiomatous proliferation. Eighty-five eyes were treatment-naïve; 42 eyes were treated previously: anti-vascular endothelial growth factor (VEGF) therapy (n = 26), photodynamic therapy (n = 3), and combined therapy (n = 13). Treatment of SMHs included vitrectomy (36 eyes), pneumatic displacement (49 eyes), and anti-VEGF monotherapy (42 eyes). The final BCVA improved significantly in treatment-naïve cases from 0.86 to 0.62 logarithm of the minimal angle of resolution (logMAR) unit (Snellen equivalent from 20/145 to 20/83) and from 0.80 to 0.56 (Snellen equivalent from 20/126 to 20/73) in PCV cases. Meanwhile, the BCVA logMAR values improved from 1.15 to 0.75 (Snellen equivalent from 20/283 to 20/112) and from 0.87 to 0.63 (Snellen equivalent from 20/148 to 20/85) in eyes that underwent vitrectomy or pneumatic displacement, respectively. In eyes with BCVAs between 20/133 to 20/40 at SMH onset, the final VA in the pneumatic displacement group was better than in the anti-VEGF monotherapy group. One eye had a retinal detachment and 1 eye had a macular hole in the vitrectomy group, and 5 eyes had a vitreous hemorrhage in the pneumatic displacement group. CONCLUSIONS: The recommended treatment for SMHs secondary to nAMD exceeding 2 disc area and with BCVA below 20/40 is vitrectomy or pneumatic displacement for visual improvement.

AIR VERSUS SULFUR HEXAFLUORIDE GAS TAMPONADE IN VITRECTOMY FOR UNCOMPLICATED RETINAL DETACHMENT WITH INFERIOR BREAKS.

PURPOSE: To compare surgical outcomes of filtered air and sulfur hexafluoride (SF6) as an internal tamponade in patients undergoing primary 25-gauge pars plana vitrectomy for uncomplicated rhegmatogenous retinal detachment with inferior breaks. METHODS: Patients with uncomplicated rhegmatogenous retinal detachment associated with inferior breaks (between 4 and 8 o'clock positions) who were undergoing primary pars plana vitrectomy were enrolled. All eyes underwent pars plana vitrectomy and complete drainage of subretinal fluid, followed by filtered air or 20% SF6 tamponade. The main outcome measures included single-surgery anatomical success rates and final visual recovery. RESULTS: Overall, 116 eyes of 116 patients (81 men and 35 women with a mean age of 55.2 years) were assessed. Air was used in 52 eyes (air group) and gas in 64 eyes (gas group). Single-surgery anatomical success was achieved in 50 (96.2%) and 60 (93.8%) eyes in the air and gas groups, respectively (P = 0.69), and final anatomical success was achieved in all eyes. The mean final Snellen visual acuity was similar in the air (20/23) and gas groups (20/21; P = 0.13). CONCLUSION: No significant differences were observed in single-surgery anatomical success rates and final visual recovery when comparing air with SF6 gas tamponade in pars plana vitrectomy for primary uncomplicated rhegmatogenous retinal detachment with inferior breaks.