Photocoagulation or sham laser in addition to conventional anti-VEGF therapy in macular edema associated with TelCaps due to diabetic macular edema or retinal vein occlusion (TalaDME): a study protocol for a multicentric, French, two-group, non-commercial, active-control, observer-masked, non-inferiority, randomized controlled clinical trial.

BACKGROUND: Macular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe visual acuity loss. Current standard of care consists in using intravitreal injections (IVI), which results in a significant medical and economic burden. During diabetic retinopathy (DR) or retinal vein occlusion (RVO), it has recently been shown that focal vascular anomalies (capillary macro-aneurysms, also termed TelCaps) for telangiectatic capillaries may play a central role in the onset, early recurrence, and/or persistence of ME. Since targeted photocoagulation of TelCaps may improve vision, identification, and photocoagulation of TelCaps, it may represent a way to improve management of ME. OBJECTIVE: The Targeted Laser in (Diabetic) Macular Edema (TalaDME) study aims to evaluate whether ICG-guided targeted laser (IGTL), in association with standard of care by IVI, allows reducing the number of injections during the first year of treatment compared with IVI only, while remaining non-inferior for visual acuity. METHODS: TalaDME is a French, multicentric, two-arms, randomized, sham laser-controlled, double-masked trial evaluating the effect of photocoagulation of TelCaps combined to IVI in patients with ME associated with TelCaps. Patients with vision loss related to center involved ME secondary to RVO or DR and presenting TelCaps are eligible. Two hundred and seventy eyes of 270 patients are randomized in a 1:1 ratio to standard care, i.e., IVI of anti-VEGF solely (control group) or combined with IGTL therapy (experimental group). Stratification is done on the cause of ME (i.e., RVO versus diabetes). Anti-VEGF IVI are administered to both groups monthly for 3 months (loading dose) and then with a pro re nata regimen with a monthly follow-up for 12 months. The primary endpoint will be the number of IVI and the change in visual acuity from baseline to 12 months. Secondary endpoints will be the changes in central macular thickness, impact on quality of life, cost of treatment, and incremental cost-utility ratio in each groups. KEY SAFETY: Rare but severe AE linked to the use of IVI and laser, and previously described, are expected. In the sham group, rescue laser photocoagulation may be administered by the unmasked investigator if deemed necessary at month 3. DISCUSSION: The best management of ME associated with TelCaps is debated, and there have been no randomized study designed to answer this question. Given the fact that TelCaps may affect 30 to 60% of patients with chronic ME due to DR or RVO, a large number of patients could benefit from a specific management of TelCaps. TalaDME aims to establish the clinical and medico-economic benefits of additional targeted laser. The results of TalaDME may raise new recommendations for managing ME and impact healthcare costs. TRIAL REGISTRATION: EudraCT: 2018-A00800-55/ NCT03751501. Registration date: Nov. 23, 2018.

A comparative study of cystoid macula edema following glaucoma drainage device surgery versus trabeculectomy.

PURPOSE: To assess and compare the risk for development of cystoid macula edema (CME) after glaucoma drainage device (GDD) implantation versus conventional trabeculectomy with mitomycin (trab) for glaucoma. METHODS: Retrospective review of consecutive patients receiving trab or GDD implantation between 2016 and 2018. Inclusion criteria were availability of pre- and postoperative spectral domain optical coherence tomography (SD-OCT) of the macula. SD-OCT images were evaluated for presence of CME qualitatively, central subfield thickness (CST) and macular volume (MV). RESULTS: 73 eyes could be included, 42 received trab and 31 GDD surgery. Eyes receiving trab on average had 0.8 ± 0.8 previous intraocular operations, while eyes with GDD implantation had 3.1 ± 1.9 (p < 0.001). Occurrence of postoperative CME was significantly more frequent after GDD implantation (6 out of 31 (19.4%)) than after trab (2 out of 42 eyes = 4.8%), (p = 0.049). Mean preoperative CST as well as MV was comparable in both groups (CST before trab: 282.7 ± 23.0 µm, CST before GDD 284.2 ± 27.3 µm, p = 0.287; MV before trab: 7.8 ± 1.1 mm3, MV before GDD: 8.0 ± 0.8mm3, p = 0.305). Mean postoperative CST and MV were significantly higher after GDD (CST 338.5 ± 129.3 µm, MV 8.8 ± 2.6 mm3) than after trabeculectomy (CST 290.6 ± 60.2 µm, p = 0.038; MV 7.8 ± 1.2mm3, p = 0.039). CONCLUSIONS: In real-life conditions, GDD surgery seems to be associated with a higher risk to develop CME when compared to conventional trabeculectomy. This information may be helpful for glaucoma surgeons to advise the patients on postoperative risks of surgery.

Aflibercept 5+PRN with retinal laser photocoagulation is more effective than retinal laser photocoagulation alone and aflibercept 3+PRN with retinal laser photocoagulation in patients with high-risk proliferative diabetic retinopathy and diabetic macular edema: a 12-month clinical trial.

Objective: This study aimed to investigate and compare the efficacy and safety of retinal laser photocoagulation (PRP) alone, PRP with aflibercept 3+PRN, and PRP with aflibercept 5+PRN in patients with both high-risk proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). Methods: Overall, 170 patients with high-risk PDR and DME (170 eyes from 170 patients) who visited our ophthalmology clinic from December 2018 to December 2020 were divided into the PRP (n=58), aflibercept 5+PRN with PRP (n=53), and aflibercept 3+PRN with PRP (n= 59) groups. General information, such as age, sex, and eye category, was obtained. Moreover, best-corrected visual acuity (BCVA), baseline central macular foveal thickness (CFT), microaneurysm (MA), area of neovascularization (NV), area of hard exudate (HE), and cytokine levels in atrial fluid before and after treatment, were assessed. The χ2 test was used for comparison between groups for statistical data. Analysis of variance was used for the statistical description of measurement data, independent samples were analyzed using Student's t-test, and Student-Newman-Keuls test was used for group comparisons. Differences were considered statistically significant at P < 0.05. Results: After treatment, no significant improvement in the BCVA (logMAR) of patients in the PRP group was observed. The BCVA (log MAR) decreased from 0.72 ± 0.17 and 0.74 ± 0.17 to 0.50 ± 0.13 and 0.53 ± 0.17 in PRP with aflibercept 5+PRN and PRP with aflibercept 3+PRN groups, respectively, with a statistically significant difference compared to those in the PRP group (P<0.05 in all cases). However, no statistically significant difference was observed between the combined treatment groups (P>0.05). The CFT in the PRP-only group decreased slightly from 361.80 ± 36.70 µm to 353.86 ± 40.88 µm, with no statistically significant difference (P>0.05), whereas the CFT in the aflibercept 5+PRN with PRP and aflibercept 3+PRN with PRP groups decreased from 356.57 ± 37.57 µm and 358.17 ± 44.66 µm to 284.87 ± 31.52 µm and 303.19 ± 37.00 µm, respectively, with statistically significant differences before and after treatment (P<0.05 for both groups). Statistically significant differences were observed in CFT between the three groups after treatment (P<0.05 in all cases). The number of MA (pcs) in the PRP, aflibercept 5+PRN with PRP, and aflibercept 3+PRN with PRP groups decreased from 118.34 ± 27.96, 118.60 ± 33.34, and 116.59 ± 28.95 to 92.95 ± 29.04, 44.60 ± 20.73, and 54.26 ± 25.43, respectively. The two-way comparison of the three groups revealed statistically significant differences in MA (P<0.05 in all cases). In the three groups, NV decreased from 1.00 ± 0.21 mm², 1.01 ± 0.18 mm², and 0.98 ± 0.20 mm² before treatment to 0.49 ± 0.17 mm², 0.31 ± 0.16 mm², and 0.38 ± 0.14 mm², respectively, with statistically significant differences (P<0.05 in all cases). After 12 months of treatment, 13, 18, and 18 patients had reduced HE area in the PRP-only, aflibercept 5+PRN with PRP, and aflibercept 3+PRN with PRP groups, respectively, with statistically significant differences (P<0.05 in all cases). After 12 months of treatment, vascular endothelial growth factor, monocyte chemoattractant protein-1, and glial fibrilliary acidic protein levels (pg/mL) in the aqueous humor decreased in both combined treatment groups compared with that at baseline, with statistically significant differences; however, no significant difference was observed between the two combined treatment groups (P>0.05). Conclusion: Aflibercept 5+PRN combined with PRP was safe and effective in treating patients with high-risk PDR and DME, and was more effective than PRP-only and aflibercept 3+PRN with PRP in improving CFT and MA.

Clinical efficacy of subthreshold micropulse laser combined with anti-VEGF drugs in the treatment of diabetic macular edema: A meta-analysis.

BACKGROUND: To systematically evaluate the efficacy and safety of subthreshold micropulse laser (SML) combined with anti-vascular endothelial growth factor (VEGF) drugs for the treatment of diabetic macular edema (DME). METHODS: The randomized controlled trials on SML combined with anti-VEGF drugs for DME were retrieved from China National Knowledge Infrastructure, Wan Fang Data, VIP Data, Sino Med (China Biomedical Literature Database), PubMed, Web of Science, The Cochrane Library, and Embase by computer from inception to April 19, 2022. The observation group was treated with SML combined with anti-VEGF drugs, while the control group was treated with anti-VEGF agents alone or SML. And the references of the included literature were manually searched. The Meta-analysis was performed using Revman 5.4 and STATA SE 15. RESULTS: This study finally included 15 randomized controlled trials involving 891 eyes for Meta-analysis. The results showed that there was no statistically significant difference between the 2 groups in best-corrected visual acuity at 1, 3, 6, 9, and 12 months after treatment. There was no statistical difference between the 2 groups in central macular thickness (CMT) at 1, 3, and 6 months after treatment (P > .05). CMT in the observation group was lower than that in the control group at 9 and 12 months (P < .05). There was no statistical difference between the 2 groups in total macular volume at 3, 6, 9, and 12 months in CMT (P > .05). The number of anti-VEGF drugs injections in the observation was lower than that in the control group (P < .05). The occurrence of complications between the 2 groups was not statistically significant difference (P > .05). CONCLUSION: SML in combination with anti-VEGF drugs in patients with DME are comparable in reducing the number of anti-VEGF drugs injections and CMT, thereby reducing the financial burden on patients. It does not differ in best-corrected visual acuity and total macular volume.

Subthreshold micropulse diode laser treatment in diabetic macular edema: biological impact, therapeutic effects, and safety.

PURPOSE: To introduce the treatment of diabetic macular edema (DME) with subthreshold micropulse diode laser (SMPL), to summarize the biological impact, therapeutic effects, and safety of this treatment, and to discuss the response to DME when SMPL is combined with anti-vascular endothelial growth factor (anti-VEGF) or steroid. METHODS: The literature search was performed on the PubMed database, with a selection of English-language articles published from 2000 to 2023 with the following combinations of search terms: diabetes macular (o) edema, micropulse laser or subthreshold micropulse laser, anti-vascular endothelial growth factor, and steroid. RESULTS: SMPL is a popular, invisible retinal laser phototherapy that is inexpensive, safe, and effective in the treatment of DME. It can selectively target the retinal pigment epithelium, reduce the expression of pro-inflammatory factors, promote the absorption of macular edema, and exert a similar and lasting clinical effect to traditional lasers. No significant difference was found in the therapeutic effects of SMPL between different wavelengths. However, HbA1c level and pretreatment central macular thickness (CMT) may affect the therapeutic outcomes of SMPL. CONCLUSION: SMPL has a slow onset and produces lasting clinical effects similar to conventional photocoagulation. It has been reported that SMPL combined with the intravitreal anti-VEGF injection can significantly reduce the number of injections without influencing the therapeutic effect, which is essential for clinical applications and research. Although 577 nm SMPL is widely used clinically, there are no standardized protocols for SMPL. Additionally, some important problems regarding the treatment of SMPL require further discussion and exploration.

Changes in Metamorphopsia in Patients Undergoing Treatment for Vitreoretinal Disorders.

PURPOSE: To quantify and compare the severity of metamorphopsia in patients undergoing vitrectomy for vitreoretinal disorders. METHODS: Data were collected evaluated from 319 patients with vitreoretinal disorders, including epiretinal membrane (ERM), macular hole (MH), cystoid macular edema with branch retinal vein occlusion (BRVO-CME), CME with central retinal vein occlusion (CRVO), diabetic macular edema (DME), macula-off rhegmatogenous retinal detachment (M-off RD), and macula-on RD (M-on RD). Metamorphopsia was recorded with the M-CHARTS preoperatively and at 3 and 6 months postoperatively. RESULTS: Preoperative and 6-month postoperative metamorphopsia scores were 0.69 ± 0.50 and 0.50 ± 0.52, respectively. Before surgery, 94% of patients presented with metamorphopsia (score ≥0.2). Preoperative metamorphopsia scores were significantly correlated with postoperative metamorphopsia scores (r = 0.378, p < 0.0001). Preoperative metamorphopsia score was significantly higher for ERM (0.89) than for DME (0.51). Vitrectomy significantly improved metamorphopsia in ERM and MH but not in the other disorders. In contrast, treatment improved visual acuity for all disorders except CRVO-CME and M-on RD. CONCLUSION: This quantitative study indicated that metamorphopsia is present in most patients undergoing surgery for vitreoretinal diseases and is most severe in ERM. In these patients, vitrectomy improved visual acuity but not metamorphopsia.

Subthreshold Compared with Threshold Macular Photocoagulation for Diabetic Macular Edema: A Systematic Review and Meta-Analysis.

TOPIC: To compare the efficacy and safety of subthreshold macular laser to conventional focal laser photocoagulation for the treatment of vision loss secondary to diabetic macular edema (DME). CLINICAL RELEVANCE: Macular laser remains an important and cost effective treatment option for vision loss secondary to DME. Although anti-VEGF therapy is often first-line, macular laser is of utility in low-resource or remote settings, for patients at risk of loss to follow-up, and for DME not meeting country-specific reimbursement criteria for anti-VEGF therapy. Subthreshold laser is a modality that does not produce clinical or histologic evidence of thermal damage, thereby potentially limiting the common complications of conventional laser. METHODS: Ovid MEDLINE, EMBASE, and CENTRAL databases were searched for randomized controlled trials (RCTs) from inception to September 28, 2022. Meta-analyses were performed using random-effects modeling. Data were collected at 12 and 24 months for best-corrected visual acuity (BCVA), central retinal thickness, diabetic retinopathy severity scale, rate of adverse events, rate of enrolled patients not completing treatment, rate of patients receiving retreatment, and quality-of-life measures. The risk of bias and certainty of evidence were assessed using Cochrane's Risk-of-Bias version 2 and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) frameworks, respectively. Subgroup analysis was performed between subthreshold laser modalities and evaluated with Instrument to assess the Credibility of Effect Modification Analyses tool. RESULTS: Fourteen RCTs comprising 514 eyes receiving conventional laser and 574 eyes receiving subthreshold laser were included. Subthreshold laser likely results in no difference to BCVA (moderate GRADE certainty) compared with conventional laser. Conventional laser demonstrated a small, statistically significant improvement in central retinal thickness (low GRADE certainty); however, the magnitude of this improvement is unlikely to be clinically important. There may not be a difference in the rate of adverse events (low GRADE certainty) at 12 months when comparing subthreshold laser to conventional laser for DME. CONCLUSION: Randomized controlled trial literature to date suggests subthreshold laser to be as effective as conventional laser in the treatment of DME. Increased follow-up duration is needed to observe any long-term safety benefit from reduced retinal damage. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PRIMARY OCCLUSIVE PANVASCULITIS WITH SEGMENTAL PERIARTERIAL PLAQUES.

PURPOSE: The purpose of this study was to describe a new clinical entity of bilateral occlusive panvasculitis with segmental periarterial plaques and its clinical course in two patients. METHODS: This was a retrospective chart review. RESULTS: Two patients with no medical history of any systemic inflammatory diseases presented with bilateral segmental periarterial plaques (Kyrieleis plaques), cotton wool spots, and microaneurysms. Segmental leakage, staining, and vascular occlusions involved the arterioles, venules, and capillaries. Leakage from the superficial capillary plexus in some areas bordering deep capillary plexus nonperfusion was observed. Both had recurrent episodes of vascular occlusions, normal brain MRI, and audiology tests. Complete workup including serology for infections, inflammatory markers, and antibody titers was unremarkable. They were started on with corticosteroids and immunosuppressant, and there were no further vascular occlusions. Both developed neovascularization adjacent to the areas of capillary nonperfusion. The second patient also developed vitreomacular traction and cystoid macular edema. He required intravitreal anti-VEGF injection, sector laser photocoagulation, and underwent a vitrectomy with membrane peeling. At the last visit, the visual acuity was 20/30 in both eyes for the first patient and 20/20 in the right eye and 20/40 in the left eye for the second patient, 12 and 6.5 years after initial presentation, respectively. CONCLUSION: Both patients presented with findings of bilateral panvasculitis with prominent segmental periarterial plaques and had repeated episodes of vascular occlusions before corticosteroid and immunosuppressants treatment, after which no additional occlusions were observed. We propose that the constellation of findings constitutes a novel clinical entity, occlusive panvasculitis with segmental periarterial plaques.

Use of Ranibizumab for evaluating focal laser combination therapy for refractory diabetic macular edema patients: an exploratory study on the RELAND trials.

Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for diabetic macular edema (DME), but is less effective in some patients. We conducted a prospective study to determine whether laser combination therapy with anti-VEGF was more effective than Ranibizumab monotherapy in anti-VEGF-resistant DME patients. There was no significant difference in the improvement of the best-corrected visual acuity (BCVA) between the laser combination therapy and Ranibizumab monotherapy groups (3.2 letters and -7.5 letters, p = 0.165). BCVA did not significantly change between visits 1 and 7 (the laser combination group, 64.3 letters 70.3 letters, respectively, p = 0.537; the Ranibizumab monotherapy group, 72.3 letters and 64.8 letters, respectively, p = 0.554), with no significant improvements in central foveal retinal thickness (the laser combination therapy group, 9.3%: the Ranibizumab monotherapy groups, - 7.3%; p = 0.926). There was no significant difference in the number of Ranibizumab intravitreal therapy (IVT) sessions between the groups (laser combination therapy, 5.2; ranibizumab monotherapy, 6.0; p = 0.237). This study did not show that laser combination therapy was significantly more effective for anti-VEGF-resistant DME than anti-VEGF monotherapy alone. Therefore, for anti-VEGF-resistant DME, alternative therapeutic approaches beyond combined laser therapy may be considered.

Subthreshold micropulse laser versus standard laser for the treatment of central-involving diabetic macular oedema with central retinal thickness of <400µ: a cost-effectiveness analysis from the DIAMONDS trial.

OBJECTIVES: To estimate the economic costs, health-related quality-of-life outcomes and cost-effectiveness of subthreshold micropulse laser (SML) versus standard laser (SL) for the treatment of diabetic macular oedema (DMO) with central retinal thickness (CRT) of <400µ. DESIGN: An economic evaluation was conducted within a pragmatic, multicentre, randomised clinical trial, DIAbetic Macular Oedema aNd Diode Subthreshold. SETTING: 18 UK Hospital Eye Services. PARTICIPANTS: Adults with diabetes and centre involving DMO with CRT<400µ. INTERVENTIONS: Participants (n=266) were randomised 1:1 to receive SML or SL. METHODS: The base-case used an intention-to-treat approach conducted from a UK National Health Service (NHS) and personal social services (PSS) perspective. Costs (2019-2020 prices) were collected prospectively over the 2-year follow-up period. A bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted to estimate the incremental cost per QALY gained and the incremental net monetary benefit of SML in comparison to SL. Sensitivity analyses explored uncertainty and heterogeneity in cost-effectiveness estimates. RESULTS: One participant in the SL arm withdrew consent for data to be used; data from the remaining 265 participants were included in analyses. Mean (SE) NHS and PSS costs over 24 months were £735.09 (£111.85) in the SML arm vs £1099.70 (£195.40) in the SL arm (p=0.107). Mean (SE) QALY estimates were 1.493 (0.024) vs 1.485 (0.020), respectively (p=0.780), giving an insignificant difference of 0.008 QALYs. The probability SML is cost-effective at a threshold of £20 000 per QALY was 76%. CONCLUSIONS: There were no statistically significant differences in EQ-5D-5L scores or costs between SML and SL. Given these findings and the fact that SML does not burn the retina, unlike SL and has equivalent efficacy to SL, it may be preferred for the treatment of people with DMO with CRT<400µ. TRIAL REGISTRATION NUMBERS: ISRCTN17742985; NCT03690050.

Analysis of the Macular Region Following Panretinal Photocoagulation for the Treatment of Diabetic Retinopathy Using Optical Coherence Tomography.

Background: Diabetic retinopathy (DR) is the most prevalent microvascular complication of diabetes. Panretinal photocoagulation (PRP) is the established treatment for mitigating severe visual impairment resulting from proliferative DR. Objective: This study aims to investigate the impact of PRP on the macular region in patients with DR, utilizing optical coherence tomography (OCT) for assessment. Design: An experimental study was meticulously designed, implementing PRP as the primary intervention. Setting: The investigation was conducted within the Department of Ophthalmology at the Affiliated Huaian No.1 People's Hospital, Huai'an, Jiangsu, China. Participants: A total of 120 participants diagnosed with DR and undergoing treatment at our hospital were enrolled in the study. Interventions: The participants were randomly assigned to either the control group (CG, n = 60) or the study group (SG, n = 60). The CG received conventional drug treatment involving oral iodized lecithin, while the SG received PRP. OCT was employed to monitor changes in macular fovea volume and macular retinal thickness. Primary Outcome Measures: Evaluation criteria encompassed clinical efficacy, macular fovea volume, macular retinal thickness, IL-6 and VEGF levels, incidence of adverse reactions, and quality of life in both groups. Results: The study resulted in a higher total effective rate in the SG (96.67%) compared to the CG (80.00%) (χ2 = 8.09, P < .05). Post-treatment, reductions were observed in macular fovea volume and macular retinal thickness, with significantly lower SG values than CG values (P < .05). Both serum IL-6 and VEGF levels exhibited reductions in both groups after treatment, with the SG displaying a more significant decrease compared to the CG (P < .05). The occurrence of adverse reactions significantly decreased in the SG relative to the CG (P < .05). Quality of life scores for the SG was notably elevated compared to the CG (P < .05). Conclusions: PRP emerges as a highly valuable approach in the management of DR. It contributes to retinal thickness improvement within the macular region and inflammation reduction, and also enhances therapeutic outcomes, minimizes adverse reactions, and optimizes patients' quality of life. These findings warrant further clinical adoption and widespread promotion.

The evolving therapeutic landscape of diabetic retinopathy.

INTRODUCTION: Diabetic retinopathy (DR) is a leading cause of blindness worldwide. Recent decades have seen rapid progress in the management of diabetic eye disease, evolving from pituitary ablation to photocoagulation and intravitreal pharmacotherapy. The advent of effective intravitreal drugs inhibiting vascular endothelial growth factor (VEGF) marked a new era in DR therapy. Sustained innovation has since produced several promising biologics targeting angiogenesis, inflammation, oxidative stress, and neurodegeneration. AREAS COVERED: This review surveys traditional, contemporary, and emerging therapeutics for DR, with an emphasis on anti-VEGF therapies, receptor tyrosine kinase inhibitors, angiopoietin-Tie2 pathway inhibitors, integrin pathway inhibitors, gene therapy 'biofactory' approaches, and novel systemic therapies. Some of these investigational therapies are being delivered intravitreally via sustained release technologies for extended durability. Other investigational agents are being delivered non-invasively via topical and systemic routes. These strategies hold promise for early and long-lasting treatment of DR. EXPERT OPINION: The evolving therapeutic landscape of DR is rapidly expanding our toolkit for the effective and durable treatment of blinding eye disease. However, further research is required to validate the efficacy of novel therapeutics and characterize real world outcomes.

The Role of Laser Photocoagulation in Treating Diabetic Macular Edema in the Era of Intravitreal Drug Administration: A Descriptive Review.

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.

Therapeutic Efficacy of Intravitreal Conbercept Injections with or without Focal Macular Photocoagulation for Diabetic Macular Edema.

Objective: This study aimed to investigate the effectiveness and safety of intravitreal conbercept injections with or without focal macular photocoagulation in the treatment of diabetic macular edema (DME). Methods: This retrospective study included 60 DME patients (60 eyes) divided into two treatment groups. The conbercept group received monthly intravitreal injections for 5 consecutive sessions, while the combination therapy group received intravitreal injections and focal macular photocoagulation. Changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were observed before and at months 1, 3, 6, 9, and 12 after treatment in both groups, along with the number of intravitreal conbercept injections administered. Results: At 1, 3, 6, 9, and 12 months after treatment, both the conbercept and combined treatment groups showed improvement in best-corrected visual acuity (BCVA) and decrease in central macular thickness (CMT) compared to before treatment, with statistical significant differences (P < .05). However, the differences in BCVA and CMT between the two groups at each time point after treatment were not significant (P > .05). During the 1-year follow-up period, the mean number of injections in the combined treatment group was 6.3±0.8, which was less than that in the conbercept treatment group (7.6 ± 0.9), with a significant difference (t = 5.556, P < .001). The incidence of subconjunctival hemorrhage was 10.9% and 10.5% in the two groups, respectively, with no significant inter-group difference (χ² = 0.013, P = .908). None of the patients exhibited serious treatment-related ocular and systemic complications during the treatment period. Conclusions: Treatment of DME with intravitreal conbercept injections, whether with or without focal macular photocoagulation, is safe and effective in improving the patients' visual acuity and retinal anatomy. However, patients who receive combined treatment require fewer intravitreal injections than those who receive conbercept treatment alone.

Navigated direct photocoagulation with a 30-ms short-pulse laser for treating microaneurysms in diabetic macular edema exhibits a high closure rate.

This study carried out direct photocoagulation for treating microaneurysms (MAs) in diabetic macular edema (DME) using a navigation laser system with a 30-ms pulse duration. The MA closure rate after 3 months was investigated using pre and postoperative fluorescein angiography images. MAs primarily inside the edematous area based on optical coherence tomography (OCT) maps were selected for treatment, and leaking MAs (n = 1151) were analyzed in 11 eyes (eight patients). The total MA closure rate was 90.1% (1034/1151), and the mean MA closure rate in each eye was 86.5 ± 8.4%. Mean central retinal thickness (CRT) decreased from 471.9 ± 73.0 µm to 420.0 ± 87.5 µm (P = 0.049), and there was a correlation between the MA closure rate and the CRT reduction rate (r = 0.63, P = 0.037). There was no difference in the MA closure rate depending on the degree of edema thickness based on a false-color topographic OCT map image. Direct photocoagulation for DME with a short pulse using the navigated photocoagulator resulted in a high MA closure rate in just 3 months and a corresponding improvement in retinal thickness. These findings encourage the use of a new therapeutic approach for DME.

Surgical Management of Diabetic Macular Edema.

PURPOSE OF REVIEW: Diabetic macular edema (DME) is the accumulation of fluid in the extracellular space within the macula and is a major cause of visual impairment among patients with diabetes. First-line treatment for DME includes pharmacotherapy with intravitreal anti-vascular endothelial growth factor medications and intravitreal corticosteroids. Alternative therapeutic strategies include laser photocoagulation for non-center involving DME, and surgical options such as pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peel in cases with vitreoretinal interface anomalies or DME refractory to pharmacotherapy, and the Port Delivery System (PDS) for sustained release of anti-vascular endothelial growth factor (VEGF) medication. Our aim is to review the existing literature on surgical management of DME including imaging changes in chronic DME and the clinical relevance of surgical intervention. RECENT FINDINGS: Imaging changes associated with DME and a worse prognosis include disorganization of the retinal layer, disruption of both the external limiting membrane (ELM) and ellipsoid zone, and vitreomacular interface abnormalities. Studies involving pars plana vitrectomy with and without ILM peel show anatomic improvement but may not always be associated with significant change in visual outcomes. Early studies lacked detailed imaging of the retinal layers and PPV was likely performed as a last resort. In addition, the novel PDS is surgically implanted into the pars plana and works as a drug reservoir with controlled release of drug. However, it has been recalled in patients with wet age-related macular degeneration due to issues with dislodgement. Surgical interventions for DME include pars plana vitrectomy with and without ILM peel and new surgical therapies for DME such as the PDS and subretinal gene therapy have the potential to reduce the risk of DME progression.

Indications and outcomes of intraocular Lens Exchange among pseudophakic eyes in a Tertiary Referral Center.

PURPOSE: To determine the indications and surgical outcomes of intraocular lens (IOL) exchange in pseudophakic patients at Labbafinejad Tertiary Referral Center between 2014 and 2019. METHODS: In this retrospective interventional case series, the medical records of 193 patients with a history of IOL exchange were reviewed. Preoperative data, including clinical characteristics, indications of the first and second IOL implantation, intra- and postoperative complications due to IOL exchange, and the pre-and postoperative refractive error and best-corrected visual acuity (BCVA) were considered the outcome measures in this study. All postoperative data were analyzed at least six months after follow-up. RESULTS: The mean age of our participants was 59.13 ± 20.97 years old at the time of the IOL exchange, with a male percentage of 63.2%. The mean follow-up after the IOL exchange was 15.72 ± 16.28 months. The main indications of IOL exchange were IOL decentration (50.3%), corneal decompensation (30.6%), and residual refractive errors (8.3%). 57.10% of patients with the postoperative spherical equivalent at -2.00 diopter (D) to + 2.00D. The mean best-corrected visual acuity was 0.82 ± 0.76 LogMAR before the IOL exchange and was improved to 0.73 ± 0.79 LogMAR after the surgery. Corneal decompensation (6.2%), glaucoma (4.7%), retinal detachment (4.1%), cystoid macular edema (2.1%), and uveitis (1%) were found as the postoperative complications. There was only one case with suprachoroidal hemorrhage during IOL exchange. CONCLUSIONS: IOL decentration followed by corneal decompensation was the most common indication of IOL exchange. After IOL exchange, the most complications during follow-up were corneal decompensation, glaucoma, retinal detachment, and cystoid macular edema.

Intravitreal anti-vascular endothelial growth factor, laser photocoagulation, or combined therapy for diabetic macular edema: A systematic review and network meta-analysis.

Purpose: To conduct a network meta-analysis (NMA) comparing the efficacy of anti-vascular endothelial growth factor (VEGF) therapy alone versus laser photocoagulation (LP) therapy alone or anti-VEGF therapy combined with LP therapy for diabetic macular edema (DME). Methods: PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were systematically searched for studies comparing anti-VEGF therapy alone versus LP therapy alone or anti-VEGF therapy combined with LP therapy for DME. Primary outcomes were mean best-corrected visual acuity (BCVA) and central macular thickness (CMT) change. Relevant data were collected and pooled using NMA. Results: A total of 13 randomized controlled trials were included in our NMA. Anti-VEGF therapy significantly improved BCVA the most compared to the combined (mean difference [MD] = 1.5; 95% confidence interval [CI]: 0.084, 2.7) and LP (MD = 6.3; 95% CI: 5.1, 7.6) therapies at six months, while there was no difference in reducing CMT at six months between the anti-VEGF and combined therapies (MD = -16; 95% CI: -46, 13). At 12 months, no significant difference was found between the anti-VEGF and combined therapy in terms of BCVA (MD = 0.1; 95% CI: -1.7, 1.5) and CMT (MD = 21; 95% CI: -3.0, 44). Conclusion: There was no significant difference between the anti-VEGF therapy and combined therapy. For the long-term treatment of patients with DME, combined therapy is recommended. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022376401.

Outcomes of cystoid macular edema following Descemet's membrane endothelial keratoplasty in a referral center for keratoplasty in Spain: retrospective study.

The aim of this study was to analyze the outcomes of eyes with visually significant cystoid macular œdema (vs-CMO) after Descemet membrane endothelial keratoplasty (DMEK) in a referral center for keratoplasty in Spain. We conducted a retrospective, single-surgeon case series of eyes that developed post-DMEK vs-CMO performed between January 2011 and December 2020. Data collected included: indication for DMEK; biometric data; ocular comorbidities; past medical history; time to detection of vs-CMO after DMEK (T, weeks); best-corrected visual acuity (BCVA, logMAR) and central retinal thickness (CRT, µm) at diagnosis of vs-CMO, after resolution of CMO, and at last follow-up; and management strategy. Main outcomes analyzed were incidence of vs-CMO, improvement in BCVA and CRT after treatment of vs-CMO. Of 291 consecutive DMEK surgeries, 14 eyes of 13 patients (4.8%) developed vs-CMO. Five patients (38.5%) had history of CMO, and 28.6% of eyes had ophthalmic comorbidities. Median (P25-P75) T was 4 (3-10) weeks. Treatment success was observed in 12/13 eyes (92.3%), two of which required second-line treatment. In successful cases (median time-to-resolution 3.0 (2.0-3.5) months), median BCVA improved from 0.60 (0.40-0.80) logMAR to 0.30 (0.15-0.40) logMAR (p = 0.002) after treatment, and median CRT improved from 582.5 (400.0-655.0) µm to 278.0 (258.0-294.0) µm (p = 0.005). In our study, we found a 4.8% rate of post-DMEK vs-CMO, with most cases occurring in the first 3 months after surgery. Good functional and anatomical outcomes are expected in most eyes, without treatment-related complications or implications in graft outcomes. Additional studies are encouraged to determine a standardized protocol for post-DMEK vs-CMO.

Optimizing treatment for diabetic macular edema during cataract surgery.

Diabetic macular edema (DME) causes visual impairment in diabetic retinopathy (DR). Diabetes mellitus is a global epidemic and diabetic individuals are at risk of developing DR. Approximately 1 in 10 diabetic patients suffers from DME, which is the commonest cause of vision-threatening DR at primary-care screening. Furthermore, diabetes predisposes to a higher frequency and a younger onset of cataract, which further threatens vision in DME patients. Although cataract extraction is an effective cure, vision may still deteriorate following cataract surgery due to DME progression or recurrence, of which the risks are significantly higher than for patients without concurrent or previous history of DME at the time of operation. The management of pre-existing DME with visually significant cataract is a clinical conundrum. Deferring cataract surgery until DME is adequately treated is not ideal because of prolonged visual impairment and maturation of cataract jeopardizing surgical safety and monitoring of DR. On the other hand, the progression or recurrence of DME following prompt cataract surgery is a profound disappointment for patients and ophthalmic surgeons who had high expectations for postoperative visual improvement. Prescription of perioperative anti-inflammatory eye drops is effective in lowering the risk of new-onset DME after cataract surgery. However, management of concurrent DME at the time of cataract surgery is much more challenging because DME is unlikely to resolve spontaneously even with the aid of anti-inflammatory non-steroidal or steroid eye drops. A number of clinical trials using intravitreal injection of corticosteroids and anti-vascular endothelial growth factor (anti-VEGF) as first-line therapy have demonstrated safety and efficacy to treat DME. These drugs have also been administered perioperatively for the prevention of DME worsening in patients undergoing cataract surgery. This article reviews the scientific evidence to guide ophthalmologists on the efficacy and safety of various therapies for managing patients with DME who are particularly vulnerable to cataract surgery-induced inflammation, which disintegrates the blood-retinal barrier and egression of fluid in macular edema.