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Purpose: In patients with diabetic macular edema (DME) from YOSEMITE/RHINE, dual angiopoietin-2/vascular endothelial growth factor-A (VEGF-A) inhibition with faricimab resulted in visual/anatomic improvements with extended dosing. The SWAN trial (jRCTs031230213) will assess the efficacy, durability, and safety of faricimab during the treatment maintenance phase in patients with DME using a treat-and-extend (T&E)-based regimen adapted to clinical practice and the characteristics of patients achieving extended dosing intervals., Methods: SWAN is a 2-year, open-label, single-arm, interventional, multicenter trial enrolling adults with center-involving DME. All patients will receive three initial faricimab 6.0 mg doses every 4 weeks (Q4W). From week 12 onwards, in patients without active DME, dosing intervals will be extended in 8-week increments up to Q24W. In contrast, patients with active DME (central subfield thickness [CST] >325 μm and intraretinal fluid [IRF] or subretinal fluid [SRF] resulting in vision loss/disease aggravation) will receive a dose within a day and the dosing interval will be shortened by 4 weeks to a minimum of Q8W relative to the previous dosing interval. Recruitment commenced in August 2023 across a planned 16 sites in Japan., Results: The primary endpoint is change in best-corrected visual acuity (BCVA) from baseline at 1 year (averaged over weeks 52, 56, and 60). Key secondary endpoints include: change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire scores over time; proportion of patients with BCVA (decimal visual acuity) ≥0.5, ≥0.7, ≥1.0, or ≤0.1; proportion of patients with absence of DME, and IRF and/or SRF over time. Safety endpoints include incidence/severity of ocular/nonocular adverse events., Conclusions: The SWAN trial is expected to provide evidence to support individualized faricimab dosing regimens, with the potential to reduce the burden of frequent treatments on patients, caregivers, and healthcare systems., Competing Interests: Takao Hirano: Speaker Fees: Bayer, Canon, Chugai Pharmaceutical Co., Ltd., Kowa, Novartis Pharma KK, Santen Pharmaceutical Co., Senju, ZEISS Toshinori Murata: Speaker Fees: Bayer, Novartis, Santen, Zeiss Meditec: Consultant: Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Hoya, Kowa, Wakamoto Shintaro Nakao: Consultant: Alcon, Boehringer Ingelheim, Novartis, Riverfield; Speaker Fees: Bayer, Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Hoya, Kowa, Machida, Mitsubishi Tanabe, Novartis, Novo Nordisk, Otsuka, Santen, Senju, Wakamoto Masahiko Shimura: Consultant: Bayer, Boehringer Ingelheim, Chugai, HOYA, Nikki HD, Roche, Wakamoto; Lecture Fees: Bayer, Chugai, Kowa, Novartis, Otsuka, Senju Miho Nozaki: Speaker Fees: Bayer, Canon, Chugai Pharmaceutical Co., Ltd., Kowa, Nikon, Novartis Pharma KK, Santen, Senju, Sumitomo Pharma Co., Ltd., Topcon Medical, Wakamoto Kiyoshi Suzuma: Speaker Fees: AMO, Alcon, Bayer, Chugai Pharmaceutical Co., Ltd., HOYA, Kowa, Novartis, Senju Consultant: Senju, Chugai Pharmaceutical Co., Ltd., Boehringer Ingelheim Taiji Nagaoka: Consultant: Boehringer Ingelheim, Novartis, TES Holdings; Speaker Fees: Bayer, Chugai Pharmaceutical Co., Ltd., Hoya, Kowa, Mitsubishi Tanabe, Novartis, Santen, Senju, Wakamoto; Research Fees: Daicel, Kowa, LTT, Santen Masahiko Sugimoto: Research Fees: Alcon Japan, Bayer, Chugai Pharmaceutical Co., Ltd., Novartis; Speaker Fees: Alcon Japan, Bayer, Kowa, Novartis, Senju, Wakamoto Yoshihiro Takamura: Lecture Fees: Chugai Pharmaceutical Co., Ltd. Tomoaki Murakami: Speaker Fees: Bayer, Canon, Chugai Pharmaceutical Co., Ltd., Johnson & Johnson, Kowa, Novartis Pharma KK, Santen; Consultant: Boehringer Ingelheim Keisuke Iwasaki: Employee: Chugai Pharmaceutical Co., Ltd. Jun Tsujimura: Employee: Chugai Pharmaceutical Co., Ltd. Shigeo Yoshida: Consultant: Chugai Pharmaceutical Co., Ltd., Novartis; Speaker Fees: Bayer, Chugai Pharmaceutical Co., Ltd., Novartis, Senju; Research Fees: Kowa, Otsuka, Senju We confirm that the author competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Hirano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives : This study aimed to elucidate the role of laser photocoagulation therapy in the treatment of diabetic macular edema (DME) as an alternative to, or in conjunction with, the first-line treatment, anti-vascular endothelial growth factor (VEGF). Materials and Methods : A comprehensive literature search to identify studies that evaluated the efficacy of laser photocoagulation therapy in the management of DME was performed. The relevant findings of the efficacy of focal/grid laser therapy from data in randomized, controlled trials were synthesized, and the potential of new laser technologies, such as navigated laser systems, pattern scan lasers, and subthreshold lasers, was explored. The usefulness of multimodal imaging-guided laser therapy was also evaluated, with a focus on the potential contribution to anti-VEGF therapy. Results : Focal laser photocoagulation targeting microaneurysms remains an effective therapeutic approach to chronic refractory edema, despite the widespread use of anti-VEGF therapy. To achieve the best possible treatment outcomes, precise identification of microaneurysms is essential. This requires the use of multimodal imaging-guided, highly accurate, minimally invasive coagulation techniques. Subthreshold laser therapy can also reduce the frequency of anti-VEGF injections and minimize treatment burden. Conclusions : Further studies are needed to determine the optimal timing and settings for laser photocoagulation therapy and the potential of new laser technologies in the management of DME. Nevertheless, laser photocoagulation therapy plays an important role in the management of DME, in conjunction with anti-VEGF therapy.

Aims: To study the possibility of constructing a remote interpretation system for retinal images., Methods: An ultra-widefield (UWF) retinal imaging device was installed in the internal medicine department specializing in diabetes to obtain fundus images of patients with diabetes. Remote interpretation was conducted at Nagoya City University using a cloud server. The medical data, severity of retinopathy, and frequency of ophthalmologic visits were analyzed., Results: Four hundred ninety-nine patients (mean age, 62.5 ± 13.4 years) were included. The duration of diabetes in 240 (48.1%) patients was less than 10 years and 433 (86.7%) patients had a hemoglobin (Hb) A1c below 8%. Regarding the retinopathy severity, 360 (72.1%) patients had no diabetic retinopathy (NDR), 63 (12.6%) mild nonproliferative retinopathy (NPDR), 38 (7.64%) moderate NPDR, 13 (2.6%) severe NPDR, and 25 (5.0%) PDR. Two hundred forty-one (48.3%) patients had an ophthalmologic consultation within 1 year, 104 (20.8%) had no history of an ophthalmologic consultation. DR was not present in 86 (82.7%) patients who had never had an ophthalmologic examination, 30 (78.9%) patients with severe NPDR or PDR had had an ophthalmologic visit within 1 year. The frequency of ophthalmic visits was correlated negatively with age, diabetes duration, HbA1c, and severity of retinopathy., Conclusion: Remote interpretation of DR using UWF retinal imaging was useful for retinopathy screening. During the COVID-19 pandemic, a remote screening system that can ensure compulsory social distancing and reduce the number of ophthalmic visits can be a safe system for patients and clinicians., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Diabetic macular edema (DME), characterized by exudative fluid accumulation in the macula, is the most common form of sight-threatening retinopathy in patients with diabetes. The management of DME has changed considerably in recent years, especially following the development of intravitreal anti-vascular endothelial growth factor therapy which has emerged as a first-line therapy for center-involved DME. Laser treatment, intravitreal steroid therapy, and vitrectomy are also important treatment options for DME. We believe that it is important to choose the most appropriate treatment option for DME based on the clinical evidences, in addition to the careful consideration of individual patients' general or ocular condition, DME characteristics, patients' motivation, and compliance to the treatment in real-world clinical practice. In this review, we have summarized important clinical evidences for the main treatments for DME, presented an expert review for these evidences, and proposed a recommended therapeutic flow chart for DME. We hope that our review of the clinical evidences and the recommended therapeutic flow chart for DME will contribute to better treatment outcome for DME.

Purpose: To evaluate the efficacy of indocyanine-green angiography (ICGA)-guided navigated focal laser photocoagulation for diabetic macular edema (DME)., Study Design: Prospective, interventional case series., Methods: Six patients (8 eyes) were enrolled in this study. Fluorescein angiography (FA) and ICGA were performed using the Heidelberg Retina Angiogram 2 (Heidelberg Engineering). Navigated focal laser photocoagulation was delivered to the microaneurysms on ICGA using Navilas ® (OD-OS GmbH, Germany). Central retinal thickness (CRT) and macular volume (MV) were measured by Cirrus HD-OCT (Carl Zeiss Meditec). At 6 months, the best-corrected visual acuity (BCVA), CRT and MV were compared to the values measured on day 0. The distances from the center of fovea to the closest microaneurysms (MAs) were measured on the pre-planned Navilas ® image., Results: All eyes had previous treatment history. At 6 months, ICGA-guided navigated focal laser photocoagulation significantly reduced the CRT and the MV (p<0.05), and there was improvement in the BCVA (p<0.05). At 3 months, 5 out of the 8 eyes (63%) underwent additional ICGA-guided navigated focal laser photocoagulation due to remnants of MAs that had been confirmed by ICGA. There was no observed recurrence of edema after the ICGA-guided navigated focal laser photocoagulation during the 6-month follow-up. The mean distance from the center of fovea to the closest MAs was 624.8 ± 377.7 μm (range 336.0-1438.9 μm)., Conclusion: Our data suggest ICGA-guided navigated focal laser photocoagulation may be effective for the treatment of DME.

Purpose: To study the association between the distributions of microaneurysms detected by en face optical coherence tomography angiography (OCTA) and diabetic macular edema (DME)., Methods: The study design was a retrospective chart review of 27 patients (33 eyes) with DME. The eyes were scanned using OCTA (6 × 6 mm) and spectral-domain (SD) OCT macular cube. Each of the images of the capillary plexus was overlaid onto the image of the topographic map, and the densities of the microaneurysms were measured by ImageJ software. The association between the distribution of microaneurysms and macular edema was evaluated., Results: For microaneurysms in areas with and without edema, 77.3 ± 8.1% of these microaneurysms were located in the deep capillary plexuses (DCP). However, in areas of edema where the retinal thickness was more than 400 μm, 91.3 ± 9.1% of the microaneurysms were found in the DCP. This difference was statistically significant (P < 0.001). In the macular edema area, there was a significantly higher density of microaneurysms in the DCP compared to the superficial capillary plexuses (1.71/mm2 vs. 0.17/mm2, P < 0.001). There was also a significant correlation between the macular volume and the density of microaneurysms in the DCP in edema (r = 0.63, P < 0.001)., Conclusions: Our study demonstrated a high proportion of microaneurysms in the DCP, as well as a novel association between the distributions of microaneurysms detected by OCTA and DME. Results also indicated that microaneurysms located in the DCP contribute to the pathogenesis of DME.

Purpose: To evaluate the area of the foveal avascular zone (FAZ) detected by en face OCTA (AngioVue, Avanti OCT; Optovue) in healthy and diabetic eyes., Methods: Retrospective chart review of patients who underwent fundus examination including en face OCTA. Eyes with proliferative diabetic retinopathy and history of laser photocoagulation were excluded. The FAZ area in the superficial and deep plexus layers were measured and evaluated using ImageJ software., Results: The FAZ area in the superficial layer was 0.25 ± 0.06 mm² in healthy eyes (n = 19), whereas it was 0.37 ± 0.07 mm² in diabetic eyes without retinopathy (n = 24) and 0.38 ± 0.11 mm² in eyes with diabetic retinopathy (n = 20). Diabetic eyes showed statistically significant FAZ enlargement compared with healthy eyes, regardless of the presence of retinopathy (P < 0.01). The FAZ area in the deep plexus layer was also significantly larger in diabetic eyes than in healthy eyes (P < 0.01)., Conclusion: Our data suggest that diabetic eyes show retinal microcirculation impairment in the macula even before retinopathy develops. En face OCTA is a useful noninvasive screening tool for detecting early microcirculatory disturbance in patients with diabetes.

Purpose: The ultra-wide field scanning laser ophthalmoscope (Optos 200Tx, Optos, Scotland, UK) provides retinal images of 200 degrees in a single capture which covers more than 80% of the retina. Fluorescein angiography with Optos 200Tx is useful to visualize the microcirculations of peripheral retina. It allows to evaluate peripheral pathology more precisely than conventional fundus photography. The purpose of this study was to evaluate the fluorescein angiography findings of eyes in diabetic retinopathy patients by using ultra-wide field fluoresrein angiography., Subjects and Methods: Ultra-wide field fluoresrein angiography was performed on 154 eyes of 77 patients with diabetic retinopathy. We divided the fundus into three zones, the posterior pole, the mid-periphery and the far-periphery. Capillary non-perfusion areas and retinal neovascularization in each zone were evaluated., Results: One hundred thirty eyes (84%) exhibited capillary non-perfusion areas. Ten eyes (7.7%) were found to have a capillary non-perfusion area only in the far-periphery. Seventy two eyes (47%) exhibited retinal neovascularization. Retinal neovascularization was observed most in the mid-periphery (58 eyes; 81%); 8 eyes (11%) were found to have retinal neovascularization in the far-periphery., Conclusion: Ultra-wide field fluorescein angiography revealed the microcirculatory disturbance in the peripheral retina of diabetic patients not evident by conventional fundus photography and it was useful for evaluating the status of the diabetic retinopathy.

Purpose: To assess the efficacy and outcomes of PASCAL laser versus conventional laser for panretinal photocoagulation (PRP) in the treatment of diabetic retinopathy., Methods: A retrospective chart review of 26 eyes at Nagoya City University Hospital which had undergone PRP with a follow-up of at least 6 months. The study endpoints were change in visual outcome, central retinal thickness (CRT), laser setting parameters, and total number of PRP and complications., Results: Ten eyes of conventional laser-treated patients and 16 eyes of PASCAL-treated patients were reviewed. There were significant differences in the laser treating parameters between the PASCAL laser treatment and conventional laser treatment in power, duration, number of sessions and total spot counts including additional treatments (p < 0.01). Among the patients who had undergone PRP in the PASCAL group there was an average of 4195 spots, larger than the conventional laser group (p < 0.0001). There were no significant differences between PASCAL group and conventional laser group in complications and in ability to prevent visual loss and CRT., Conclusion: Our data suggested that PASCAL laser might need tighter spacing and more total spot counts to achieve an effect equal to traditional conventional laser treatment.

Purpose: The difference in preferences and trends of treatment in each country are important to plan an international interventional clinical study in eastern Asia. Accordingly, we compared the preferences and trends in treatment of diabetic retinopathy in Korea and Japan., Methods: We obtained answers to questionnaires (49 questions) from 91 ophthalmologists of the Korean Retina Society and 120 ophthalmologists of the Japanese Society of Ophthalmic Diabetology in June/July, 2012. Some of the questions were modified from The Preferences and Trends (PAT) survey of American Society of Retina Specialists., Results: The first choice for a patient with vision of 20/25, clinically significant diabetic macular edema and clear evidence of intraretinal fluid on spectral domain OCT were intravitreal anti-vascular endothelial growth factor agent (31%) in Korea and sub-Tenon steroid (22%) in Japan. The management for a patient with refractory neovascular glaucoma who has closed angle and persistent intraocular pressure elevation (>50 mmHg) were glaucoma drainage implant surgery (74%) in Korea and trabeculectomy (57%) in Japan., Conclusion: There were differences in preferences and trends of treatment for diabetic retinopathy between Korea and Japan. The differences need to be considered when planning international clinical studies.

Short-pulse laser is popular for its advantages like less pain. However, its effectiveness is still debated. The aim of this study was to compare fundus autofluorescence (FAF) luminosity changes of laser photocoagulation scars between the conventional laser (0.2 s) and the short-pulse laser (0.02 s) for diabetic retinopathy. Conventional and short-pulse laser photocoagulations were performed in six and seven eyes, respectively. FAF images were captured at 1, 3, 6, 12, and 18 months after the treatments. To evaluate FAF, individual gray-scale values of the laser scars adjacent to the retinal arcade vessels were recorded; then, the mean gray values of the scars were divided by the luminosity of arcade vein. The average luminosity ratio of laser scars at 1, 3, 6, 12, and 18 months were 1.51 ± 0.17, 1.26 ± 0.07, 1.21 ± 0.03, 0.95 ± 0.11, and 0.89 ± 0.05 with conventional laser and 1.91 ± 0.13, 1.50 ± 0.15, 1.26 ± 0.08, 1.18 ± 0.06, and 0.97 ± 0.04 with short-pulse laser, respectively. Findings suggest the short-pulse laser displayed delayed hypoautofluorescence progression. This implies potential postponement in post-irradiation atrophic changes, as well as metabolic amelioration delay in the ischemic retina, when compared to conventional laser treatment. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate navigated laser photocoagulation for the treatment of refractory diabetic macular edema (DME). Methods. Retrospective study of 25 eyes (21 patients) treated with Navilas 577+ focal laser system. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (OCT) parameters were measured at baseline, 1, 3, and 6 months, and final visit. Results. The mean follow-up period was 12.8 ± 2.4 (7–16 months). All subjects had history of previous treatment which was injection of triamcinolone acetonide or antivascular endothelial growth factor (VEGF) agents. The navigated laser photocoagulation was delivered to the microaneurysms on indocyanine green angiography (ICGA) in 21 of 25 eyes (84%), fluorescein angiography (FA) guided in 3 eyes, and OCT angiography guided in 1 eye. After initial navigated laser treatment, 16 of 25 eyes (64%) were needed additional navigated laser photocoagulation, injection of triamcinolone acetonide, and/or injection of VEGF agents. Although median BCVA remained stable, the central retinal thickness and macular volume were significantly decreased over 6 months (p<0.05). All patients were treated without complications. Conclusions. Focal photocoagulation using Navilas 577+ showed to be effective in treating DME with improvement in macular edema on OCT over 6 months. Navilas 577+ was beneficial to perform navigated laser photocoagulation based on three modalities (ICGA, FA, and OCT angiography). [ABSTRACT FROM AUTHOR]

Purpose. To compare the expansion rates of laser photocoagulation scars between the conventional laser and short-pulse laser using fundus autofluorescence (FAF). Methods. Retrospective chart review. Conventional laser was performed on 6 eyes of 6 patients, and short-pulse laser was performed on 11 eyes of 8 patients with diabetic retinopathy. FAF images were obtained by Optos® 200Tx (Optos, Dunfermline, Scotland, UK) at 1, 3, 6, and 12 months after treatment. The average area of 20 photocoagulation scars was measured by using ImageJ software. The expansion rates were calculated from the proportion of the averaged area against the optic disc area. Regression of retinopathy and central macular thickness were also evaluated. Results. The expansion rates of the conventional laser scars compared with the size at 1 month after treatment were 1.12 ± 0.08 (3 M), 1.27 ± 0.12 (6 M), and 1.39 ± 0.11 (12 M). The expansion rates of the short-pulse laser scars were 1.04 ± 0.05 (3 M), 1.09 ± 0.04 (6 M), and 1.13 ± 0.05 (12 M). The expansion rates of the short-pulse laser were significantly lower than those of the conventional laser (p<0.01). Conclusion. FAF images were useful to evaluate the changes in the photocoagulation scar sizes. The scars with the short-pulse laser showed lower expansion rates than those of the conventional laser. [ABSTRACT FROM AUTHOR]