Purpose: To characterize, using clustering analysis, the OCT morphological and clinical phenotypes of diabetic macular edema (DME) in a very large population (>2000 DME eyes) using standardized and validated OCT-based biomarkers. Methods: A cross-sectional study was conducted on OCT scans collected from 2355 eyes of 1688 patients with DME and performed during real-world clinical practice. OCT scans were automatically analyzed by a software able to automatically quantify OCT key biomarkers: intraretinal fluid (IRF), subretinal fluid (SRF), hyperreflective retinal foci (I-HRF), and external limiting membrane (ELM) and ellipsoid zone (EZ) interruption. Clustering analysis was performed using the above-mentioned biomarkers, including the distribution of IRF across the three ETDRS rings. Results: The overall population was predominantly composed of type 2 diabetes patients (89%), with a mean diabetes duration of 15.6 ± 10.7 years and mean best corrected visual acuity (BCVA) of 63 ± 18 ETDRS letters. Multivariate clustering identified four morphological phenotypes with distinct patterns of fluid distribution associated with different I-HRF counts, SRF volume, and percentages of ELM/EZ integrity (p < 0.0001). Conclusions: This large OCT analysis identified distinct morphological subtypes of DME, confirming the clinical relevance of key imaging biomarkers. The distribution and severity of DME features differ among clusters, supporting the importance of OCT-based phenotyping in tailoring treatment strategies and understanding disease evolution.

Introduction Intracameral cefuroxime is commonly used as a prophylaxis against endophthalmitis following cataract surgery. While its effectiveness is well-documented, concerns remain regarding potential toxicity. Intracameral cefuroxime ocular toxic syndrome (ICOTS) is characterized by acute, extensive, and serous retinal detachment that usually resolves spontaneously. However, the long-term effects of ICOTS have not yet been studied. This study aims to provide new insights into ICOTS using multimodal imaging, retinal electrophysiology, and perimetry to assess both acute and chronic functional and structural changes in eyes with a disrupted intraocular vitreous barrier. Methods This retrospective case series included four patients affected by ICOTS who underwent cataract surgery with standard-dose intracameral cefuroxime (1.0 mg/0.1 ml). Three patients had previously undergone pars-plana vitrectomy and one patient had undergone anterior vitrectomy. Patients were followed up to 1 year after surgery. Evaluations included optical coherence tomography (OCT), ultra-wide-field (UWF) OCT-angiography (OCTA), automated perimetry, and multifocal electroretinography (ERG) at the preoperative visit (T0) and at 1 day (T1), 1 week (T2), 1 month (T3), 6 months (T4), and 1 year (T5) after cataract surgery. Results At T1, all patients had acute extensive serous retinal detachments. UWF-OCTA revealed increased superficial vessel density during the acute phase, with only partial restoration at follow-up. Two cases had permanent structural damage to the outer retina. Functional assessments showed transient changes in multifocal ERG responses, returning to near-normal levels within T3. Best-corrected visual acuity worsened at T1 and improved after the subretinal fluid resolution (T2). Conclusion Intracameral cefuroxime ocular toxic syndrome may induce persistent retinal changes despite fluid resolution in eyes with a disrupted intraocular barrier due to prior vitrectomy. Early OCT assessment can help to identify this condition. Further investigation, incorporating UWF-OCTA and ERG for a comprehensive assessment of ICOTS, along with revised informed consent protocols for patients undergoing cataract surgery with this antibiotic prophylaxis, may be indicated when risk factors are identified.

Purpose: The purpose of this study was to evaluate the efficacy and safety of bevacizumab-awwb in the off-label treatment of neovascular age-related macular degeneration (n-AMD) and diabetic macular edema (DME). Methods: All patients with n-AMD and DME treated in the maintenance phase according to the “treat and extend” strategy, who underwent forced drug substitution from bevacizumab to bevacizumab-awwb from October 2022 to April 2023 at the Tor Vergata Polyclinic in Rome, were evaluated in a retrospective study. The primary outcome was changes in central retinal thickness (CRT) over time following drug substitution. The secondary outcomes were variations in drug durability, best corrected visual acuity (BCVA) and retinal fluid, and the incidence of drug-related local and systemic serious adverse events. Results: Of 80 eyes of 76 patients with n-AMD and 55 eyes of 44 patients with DME included, before and after drug substitution, the average CRT did not statistically differ; the proportion of patients within time intervals of q8, q12, and q16 was not different; and the mean BCVA remained constant. Of a cumulative 3496 bevacizumab-awwb treatments (2154 for patients with n-AMD and 1342 for patients with DME), no local severe complications were detected. Out of a total of 544 patients (342 affected by n-AMD and 202 affected by DME), no serious adverse events were reported. Conclusions: In our cohort of patients with n-AMD and DME in the maintenance phase, bevacizumab-awwb seems to represent a viable and cost-effective intravitreal therapy with comparable efficacy and safety to the originator. Translational Relevance: This study provides a preliminary assessment of the efficacy and safety of intravitreal bevacizumab-awwb, which is widely used off-label in retinal vascular diseases.

Background: Intravitreal aflibercept, ranibizumab, and bevacizumab represent the three most widely used anti-VEGF agents for the treatment of neovascular age-related macular degeneration (AMD). The objective of this study is to compare the loading phase effects of these three agents on the macular neovascularization (MNV) area and flow in treatment-naïve eyes affected by neovascular AMD, utilizing optical coherence tomography angiography (OCTA). Methods: Eighty-four neovascular AMD eyes from eighty-four patients were included in this retrospective study. Twenty-five patients were treated with aflibercept, thirty-four with ranibizumab, and twenty-five with bevacizumab within the initial loading phase preceding a treat-and-extend regimen. All patients underwent a three-monthly injection loading phase and were evaluated at baseline and one month after the loading phase. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), MNV area, and MNV flow area were assessed. MNV parameters were measured using the device-integrated “Flow Area” tool and ImageJ software. Results: Average baseline BCVA and CRT were 0.60 ± 0.22 logMAR and 343 ± 46 μm, respectively, and did not differ between groups. All three anti-VEGF agents improved anatomical and functional parameters, with no statistically significant differences between treatment groups ( p > 0.05). Aflibercept showed the most significant CRT reduction (88 μm; p < 0.01), while bevacizumab led to the highest BCVA gain (0.15 logMAR; p < 0.01). MNV area significantly decreased only in the bevacizumab group (0.26 mm2; p < 0.01), and flow area only in the ranibizumab group (0.23 mm2; p < 0.05). A strong positive correlation between MNV areas and flow areas was found at baseline ( r > 0.8) and follow-up ( r > 0.9). Conclusions: Aflibercept, ranibizumab, and bevacizumab demonstrated similar efficacy in reducing MNV area and flow and improving visual and anatomical outcomes after a three-injection loading phase. OCTA-derived flow area measurement may be a valuable and easily accessible tool in monitoring early treatment response.

Diabetic retinopathy and retinal vein occlusion represent two prevalent vision-threatening retinal diseases. Retinal laser therapy still plays an important role in treating these conditions, but its successful administration often requires referral to specialized centers and retina experts. It is, therefore, essential to develop a new treatment methodology that enables patients to benefit from the expertise of specialists from reference centers. For this purpose, we investigated the feasibility of teleguided photocoagulation conducted across continents to determine if different ophthalmologists can consensually devise and safely execute treatment plans remotely. Two patients from Italy (Europe) with diabetic retinopathy and one from Arizona (USA) with central retinal vein occlusion underwent retinal photocoagulation using Navilas^® 577s with remote teleguidance from the corresponding continental counterpart. The process included remote planning and execution, supported by an audio connection for real-time communication. Teletreatment success criteria included treatment plan completion, patient tolerance, remote connection stability, and technical quality. All treatments have been successfully performed with accurate spot application and no technical issues. Follow-ups at three weeks confirmed positive outcomes for each patient. Remote teleguided retinal photocoagulation appears feasible, offering a promising tool for global collaborations in retina care and potential benefits to regions with limited access to expert supervision.