Aims/Introduction: To determine the current clinical preferences of anti‐vascular endothelial growth factor (VEGF) treatment protocols for diabetic macular edema (DME) in Japan.Materials and Methods: This was a descriptive cross‐sectional study. Answers to a questionnaire consisting of 16 questions were obtained from 176 of 278 (63.3%) surveyed ophthalmologists.Results: The results showed that 81.2% preferred intravitreal injections of anti‐VEGF antibodies as the first‐line therapy. The most important indicators for beginning anti‐VEGF therapy were: the best‐corrected visual acuity in 44.3% and the retinal thickness in 30.7%. In the loading phase, 53.4% preferred a single injection, and in the maintenance phase, 75.0% preferred the pro re nata regimen. Financial limitation (85.8%) was reported as the most important difficulty in the treatment. For combination therapy with anti‐VEGF treatment, panretinal photocoagulation, focal photocoagulations and a sub‐Tenon steroid injection were preferred. The contraindications for anti‐VEGF therapy were: prior cerebral infarction (72.7%). Regarding the use of both approved anti‐VEGF agents in Japan, ranibizumab and aflibercept, 39.8% doctors used them appropriately.Conclusions: Our results present the current clinical preferences of anti‐VEGF treatment for DME in Japan. The best‐corrected visual acuity and the retinal thickness are important indicators to institute this therapy. The majority of the ophthalmologists use anti‐VEGF treatment as first‐line therapy and prefer the 1 + pro re nata regimen.

To evaluate the effects of intravitreal aflibercept (IVA) on the number of microaneurysms and sizes of nonperfused areas (NPAs) in eyes with diabetic macular edema (DME). Interventional, prospective study. Twenty-five eyes of 25 DME patients (average age, 64.0±8.8 years) were treated with 3 consecutive monthly IVA injections. Fluorescein angiography (FA) and OCT were performed before the IVA injections (baseline) and at 1 week after the IVA treatment. The number of microaneurysms and the ischemic index (ISI), a measure of NPA, were determined. The correlations between central retinal thickness (CRT) and number of microaneurysms and the ISI were also determined. The mean number of microaneurysms and NPA evaluated as the ISI. At baseline, the mean CRT was 485.7±90.6 μm. After treatment, the mean CRT was reduced significantly to 376.9±81.6 μm (P = 0.1 × 10-5, repeated analysis of variance). The mean number of microaneurysms was decreased significantly from 49.6±33.2 at baseline to 24.8±18.1 at 3 months after the initial treatment. This was a 50.4±21.2% reduction (P = 0.3 × 10-5, paired t test). The mean ISI was also decreased significantly from 55.5±20.4% at baseline to 28.8±16.8% after treatment (P = 0.3 × 10-5, paired t test). This was a reduction of 43.3±28.5%. A significant correlation was found between the CRT and number of microaneurysms at both baseline (r = 0.56; P = 0.004) and after treatment (r = 0.53; P = 0.006). A significant correlation was found between CRT and ISI at baseline (r = -0.39; P = 0.03) but not after treatment (r = -0.06; P = 0.79). The reduction in the number of microaneurysms was correlated with reduction in CRT.

Purpose: To report the safety and effectiveness of intravitreal aflibercept (IVT-AFL) for diabetic macular edema (DME) in the real-world clinical practice setting in Japan. Methods: In this prospective, multicenter, observational, post-marketing surveillance, patients with DME newly receiving IVT-AFL were enrolled. During a 24-month follow-up, the primary outcome was the occurrence of safety events. Other pre-specified endpoints were effectiveness indicators, such as best-corrected visual acuity (BCVA), central retinal thickness, and injection frequency. Results: In total, 646 patients administered at least one IVT-AFL injection were included in the safety analysis. During the follow-up period, adverse events occurred in 42 patients (6.50%), whereas adverse drug reactions occurred in 12 (1.86%). In the 12 patients who had adverse drug reactions, seven events occurred in seven patients within the first month of the most recent injection. In addition, 622 patients were included in the effectiveness analysis set. The number of injections over 24 months was 3.6 ± 3.0 (mean ± standard deviation [SD]). BCVA (logarithm of the minimum angle of resolution) was 0.437 ± 0.362 (mean ± SD) (n = 622) at baseline and 0.321 ± 0.348 (n = 177) after 24 months of treatment with IVT-AFL. Central retinal thickness was 440.8 ± 134.2 μm (mean ± SD) (n = 444) at baseline and 355.5 ± 126.4 μm (n = 140) at 24 months. Conclusion: Routine administration of IVT-AFL for DME was not associated with new safety concerns, and BCVA outcomes were maintained over 24 months in the real-world setting. Nonetheless, patients in this real-world setting received fewer injections than those in clinical trials, suggesting that a margin for improvement exists in clinical practice. Trial registration: ClinicalTrials.gov: NCT02425501.

To determine the efficacy of the treat and extend (TAE) protocol with intravitreal bevacizumab (IVB) for managing diabetic macular edema (DME). Retrospective, single-center study. For this retrospective study, 42 eyes of 42 patients were initially treated with 3 consecutive monthly IVB injections (loading phase), after which they were selected for different additional therapies. For the TAE protocol, the baseline treatment interval was selected to be 8 weeks and was sequentially lengthened by 2 weeks if the central macular thickness (CMT) was <300 μm at 2 consecutive examinations. Among the 42 eyes, 8 eyes (19.0%) received the TAE treatment for 2 years. The BCVA was improved significantly from 0.37 ± 0.04 before treatment to 0.19 ± 0.04 logMAR units at 2 years after the TAE determined IVB injections (P < .05). The ratio of eyes with a gain of the BCVA by more than 2 lines was 37.5%. The CMT was significantly reduced from 515.4 ± 75.5 to 303.6 ± 45.0 μm after 2 years (P < .01). The mean number of TAE injection was 8.8 and the mean injection interval was 11.0 weeks. After the loading phase, 19.0% of patients can be treated with the TAE protocol. Although significant visual improvements were obtained after the TAE protocol, it does not apply to every DME case.

Epiretinal membrane (ERM) foveoschisis is a recently proposed clinical entity. The purpose of this study was to compare the clinical characteristics and surgical outcomes of eyes with ERM foveoschisis to those of typical ERM. The medical records of all patients with ERM-related disorders examined between 2011 and 2020 were reviewed. ERM foveoschisis was defined by the clinical criteria proposed by an international panel of experts on ERMs. The background factors, clinical characteristics, and surgical outcomes of ERM foveoschisis were compared to those of typical ERM. Forty eyes with ERM foveoschisis were compared to 333 eyes with typical ERM. The percentage of women was significantly higher in the ERM foveoschisis group (92.5%) than in the typical ERM group (48.9%, p < 0.001). The central macular thickness (CMT) was significantly thinner in the ERM foveoschisis group (340 ± 110 μm) than in the typical ERM groups (476 ± 111 μm, p < 0.01). The degree of improvement in the best-corrected visual acuity (BCVA) three months after the surgery did not differ between the two groups (p = 0.59). These results suggest that the ERM foveoschisis is more likely to occur in women and that the prognosis after surgery is comparable to typical ERM.