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Daniele Veritti,1 Valentina Sarao,1,2 Valentina Soppelsa,1 Paolo Lanzetta1,2 1Department of Medicine - Ophthalmology, University of Udine, Udine, Italy; 2Istituto Europeo di Microchirurgia Oculare (IEMO), Udine, ItalyCorrespondence: Paolo LanzettaDepartment of Medicine - Ophthalmology, University of Udine, P.le Santa Maria della Misericordia 15, Udine, 33100, ItalyTel +39 0432 559907Fax +39 0432 559904Email paolo.lanzetta@uniud.itPurpose: This meta-analysis aims to summarize 12-month best-corrected visual acuity (BCVA) outcomes in response to anti-vascular endothelial growth factor (VEGF) therapy and dexamethasone implant for the treatment of diabetic macular edema (DME) and to identify factors affecting treatment response using evidence generated from meta-regression.Methods: A systematic review of electronic databases was conducted to identify randomized controlled trials (RCTs) and real-life/observational studies that reported 12-month changes in BCVA in patients with DME on anti-VEGF or dexamethasone implant treatment in monotherapy. Study factors that were analyzed are baseline patient characteristics, study type, drug employed, number of injections and 12-month change in BCVA. Data were pooled in a random-effects meta-analysis with BCVA change as the main outcome. Meta-regression was conducted to assess the impact of multiple covariates.Results: One-hundred-five heterogeneous study populations (45,032 eyes) were identified and included in the analysis. The use of anti-VEGFs and dexamethasone implant induced an overall increase of +8.13 ETDRS letters in BCVA at 12 months of follow-up. Meta-regression provided evidence that mean BCVA change using anti-VEGFs was not statistically higher for RCTs (p=0.35) compared to observational studies. Dexamethasone implant showed a trend for better results in observational studies over RCTs. Populations following a fixed aflibercept regimen performed better than those following a reactive treatment regimen. Mean BCVA gain was higher in younger populations (p< 0.001), with lower baseline BCVA (p< 0.0001) and longer diabetes duration (p< 0.0001), receiving a higher number of injections (p< 0.0001).Conclusion: Intravitreal therapy with anti-VEGFs or dexamethasone implant produces a significant improvement in BCVA at 12 months in patients with DME. Meta-regression identified the modifiable covariates that can be targeted in order to maximize functional results.Keywords: aflibercept, anti-VEGF, bevacizumab, dexamethasone, diabetic macular edema, ranibizumab

Aim: To systematically refine and recommend parameter settings of spot size, power, and treatment duration using the Pascal® photocoagulator, a multi-spot, semi-automated, short-duration laser system.Materials and Methods: A retrospective consecutive series with 752 Caucasian eyes and 1242 laser procedures over two years were grouped into, (1) 374 macular focal / grid photocoagulation (FP), (2), 666 panretinal photocoagulation (PRP), and (3) 202 barrage photocoagulation (BP). Parameters for power, duration, spot number, and spot size were recorded for every group.Results: Power parameters for all groups showed a non-gaussian distribution; FP group, median 190 mW, range 100 - 950 mW, and PRP group, median 800 mW, range 100 - 2000 mW. On subgroup comparison, for similar spot size, as treatment duration decreased, the power required increased, albeit in a much lesser proportion than that given by energy = power x time. Most frequently used patterns were single spot (89% of cases) in FP, 5 Χ 5 box (72%) in PRP, and 2 Χ 2 box (78%) in BP. Spot diameters as high as ≈ 700 μm on retina were given in the PRP group. Single session PRP was attempted in six eyes with a median spot count of 3500.Conclusion: Overall, due to the small duration of its pulse, the Pascal® photocoagulator tends to use higher powers, although much lower cumulative energies, than those used in a conventional laser. The consequent lesser heat dissipation, especially lateral, can allow one to use relatively larger spot sizes and give more closely spaced burns, without incurring significant side effects. [ABSTRACT FROM AUTHOR]

Introduction/Background: The present study has been conducted to evaluate the early effects of intravitreal erodible dexamethasone implant in patients with diabetic macular edema (DME). Methods: Eyes with DME were prospectively included in the study and received a 700-μg dexamethasone implant. Best-corrected visual acuity (BCVA) measurement, complete ophthalmic evaluation and spectral-domain optical coherence tomography were performed at baseline and 1, 2, 3, 7, 14, 21, 28, 60, and 90 days after treatment. Results: Eighteen eyes of 17 patients were included in the study. Mean central retinal thickness (CRT) decreased rapidly after treatment (p < 0.0001; repeated measures ANOVA) from 511 μm at baseline to 358 μm at day 7 and to 275 μm at the end of the follow-up. BCVA gained on average +8 ETDRS letters after one week and +8.6 letters at day 90 (p < 0.0001; repeated measures ANOVA). Conclusions: The intravitreal administration of erodible dexamethasone implant showed a fast effect in reducing CRT and improving BCVA in DME patients. Acknowledgements: None. [ABSTRACT FROM AUTHOR]

The high prevalence of Diabetic macular edema (DME) is a real global health problem. Its complex pathophysiology involves different pathways. Over the last decade, the introduction of intravitreal treatments has dramatically changed the management and prognosis of DME. Among the different treatment options, inhibitors of vascular endothelial growth factor (anti-VEGF) and intravitreal steroids implants represent the first-line therapy of DME. We conducted a review of electronic databases to compile the available evidence about the clinical management of DME in a clinical setting, with a special focus on treatment-naïve patients. Anti-VEGF therapies represent a valuable option for treating DME patients. However, many patients do not respond properly to this treatment and, due to its administration regimen, many patients receive suboptimal treatment in real life. Current evidence demonstrated that in patients with DME, DEX-i improved significantly both anatomic and visual outcomes. Besides eyes with insufficient anti-VEGF respond or recalcitrant DME cases, DEX-i can be effectively and safely used in treatment-naïve DME patients as first line therapy. DEX-i may be considered first line therapy in different clinical scenarios, such as DME eyes with a greater inflammatory component, patients with cardiovascular events, vitrectomized eyes, or those requiring cataract surgery. In conclusion, there are still many points for improvement pending in the clinical management of the patient with DME. Since DME treatment must follow a patient-tailored approach, selecting the best therapeutic approach for each patient requires a good understanding of the pathophysiology of DME., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R. Lattanzio is consultant for Allergan/Abbvie, Bayer, Novartis, SIFI. M. Varano is consultant for Allergan/Abbvie, Bayer, Novartis, Biogen, Roche. F. Boscia, C. Iaculli and D. Veritti have no conflicts of interest to declare. S. Freda, is an AbbVie employees and may own AbbVie stocks/options. B. Piergentili was a former AbbVie employee. She is now affiliated with Alnylam Italia Srl.

Diabetic macular edema (DME), defined as retinal thickening near, or involving the fovea caused by fluid accumulation in the retina, can lead to vision impairment and blindness in patients with diabetes. Current knowledge of retina anatomy and function and DME pathophysiology has taken great advantage of the availability of several techniques for visualizing the retina. Combining these techniques in a multimodal imaging approach to DME is recommended to improve diagnosis and to guide treatment decisions. We review the recent literature about the following retinal imaging technologies: optical coherence tomography (OCT), OCT angiography (OCTA), wide-field and ultrawide-field techniques applied to fundus photography, fluorescein angiography, and OCTA. The emphasis will be on characteristic DME features identified by these imaging technologies and their potential or established role as diagnostic, prognostic, or predictive biomarkers. The role of artificial intelligence in the assessment and interpretation of retina images is also discussed., Competing Interests: Declaration of Competing Interest MOG: consultant and travel grant: Bayer, Novartis, Roche; DV: consultant for Abbvie, Bayer, Novartis, Roche. MP reports personal fees from Abbvie, Novartis, Bayer, Roche, Zeiss outside the submitted work. GC, LDA, ML, MR, MCS, DV and SV declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: This study investigates the early temporal changes in pigment epithelial detachment (PED) morphology following treatment with faricimab in patients with neovascular age-related macular degeneration (nAMD). Utilizing an artificial intelligence (AI)-assisted approach, we provide a detailed quantification and characterization of the dynamics of these morphological changes., Methods: A prospective observational study was conducted on 22 eyes from 22 treatment-naïve patients with nAMD-associated PED (presenting either type 1 or type 3 macular neovascularization). Participants were administered intravitreal faricimab (6 mg) at baseline and at days 30, 60, and 90. Comprehensive ophthalmic evaluations and spectral-domain optical coherence tomography (SD-OCT) imaging were conducted at baseline and at seven additional follow-up visits on days 1, 7, 14, 30, 60, 90, and 120. An AI-based automated segmentation algorithm was utilized to precisely quantify changes in PED volume, alongside intraretinal (IRF) and subretinal fluid (SRF) volumes, at each time point., Results: Treatment with faricimab resulted in a significant reduction in mean PED volume, with an average decrease of 12% at day 1, 29% at day 7, 51% at day 14, 68% at day 30, 72% at day 60, 79% at day 90, and 84% at day 120 (p < 0.0001 for all time points). Similarly rapid and marked reductions were noted in both mean IRF (23.5% at day 1, 90.7% at day 14) and SRF (14.4% at day 1, 91.2% at day 14) volumes. The study also showed a statistically significant improvement in best-corrected visual acuity (BCVA) over the follow-up period, correlating with the reduction in PED volume., Conclusion: Faricimab demonstrates early and significant efficacy in improving PED architecture in patients with nAMD. The rapid morphological improvements observed in this study suggest faricimab may represent a valid therapeutic option for PEDs associated with nAMD., (© 2024. The Author(s).)

Purpose: This narrative review aims to provide an overview of the dangers, controversial aspects, and implications of artificial intelligence (AI) use in ophthalmology and other medical-related fields., Methods: We conducted a decade-long comprehensive search (January 2013-May 2023) of both academic and grey literature, focusing on the application of AI in ophthalmology and healthcare. This search included key web-based academic databases, non-traditional sources, and targeted searches of specific organizations and institutions. We reviewed and selected documents for relevance to AI, healthcare, ethics, and guidelines, aiming for a critical analysis of ethical, moral, and legal implications of AI in healthcare., Results: Six main issues were identified, analyzed, and discussed. These include bias and clinical safety, cybersecurity, health data and AI algorithm ownership, the "black-box" problem, medical liability, and the risk of widening inequality in healthcare., Conclusion: Solutions to address these issues include collecting high-quality data of the target population, incorporating stronger security measures, using explainable AI algorithms and ensemble methods, and making AI-based solutions accessible to everyone. With careful oversight and regulation, AI-based systems can be used to supplement physician decision-making and improve patient care and outcomes., (© 2023. The Author(s).)

Objective: To develop and validate an explainable artificial intelligence (AI) model for detecting geographic atrophy (GA) via colour retinal photographs., Methods and Analysis: We conducted a prospective study where colour fundus images were collected from healthy individuals and patients with retinal diseases using an automated imaging system. All images were categorised into three classes: healthy, GA and other retinal diseases, by two experienced retinologists. Simultaneously, an explainable learning model using class activation mapping techniques categorised each image into one of the three classes. The AI system's performance was then compared with manual evaluations., Results: A total of 540 colour retinal photographs were collected. Data was divided such that 300 images from each class trained the AI model, 120 for validation and 120 for performance testing. In distinguishing between GA and healthy eyes, the model demonstrated a sensitivity of 100%, specificity of 97.5% and an overall diagnostic accuracy of 98.4%. Performance metrics like area under the receiver operating characteristic (AUC-ROC, 0.988) and the precision-recall (AUC-PR, 0.952) curves reinforced the model's robust achievement. When differentiating GA from other retinal conditions, the model preserved a diagnostic accuracy of 96.8%, a precision of 90.9% and a recall of 100%, leading to an F1-score of 0.952. The AUC-ROC and AUC-PR scores were 0.975 and 0.909, respectively., Conclusions: Our explainable AI model exhibits excellent performance in detecting GA using colour retinal images. With its high sensitivity, specificity and overall diagnostic accuracy, the AI model stands as a powerful tool for the automated diagnosis of GA., Competing Interests: Competing interests: VS: consultant for I-Care, outside the submitted work. DV: consultant for Bayer, Novartis, Roche, outside the submitted work. ADN, MM and GF: None. PL: consultant for Aerie, Allergan, Apellis, Bausch & Lomb, Bayer, Biogen, Boehringer Ingelheim, I-Care, Genentech, Novartis, Ocular Therapeutix, Outlook Therapeutics and Roche, outside the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 was one of the most devastating public health issues in recent decades. The ophthalmology community is as concerned about the COVID-19 pandemic as the global public health community is, as COVID-19 was recognized to affect multiple organs in the human body, including the eyes, early in the course of the outbreak. Ophthalmic manifestations of COVID-19 are highly variable and could range from mild ocular surface abnormalities to potentially sight and life-threatening orbital and neuro-ophthalmic diseases. Furthermore, ophthalmic manifestations may also be the presenting or the only findings in COVID-19 infections. Meanwhile, global vaccination campaigns to attain herd immunity in different populations are the major strategy to mitigate the pandemic. As novel vaccinations against COVID-19 emerged, so were reports on adverse ophthalmic reactions potentially related to such. As the world enters a post-pandemic state where COVID-19 continues to exist and evolve as an endemic globally, the ophthalmology community ought to be aware of and keep abreast of the latest knowledge of ophthalmic associations with COVID-19 and its vaccinations. This review is a summary of the latest literature on the ophthalmic manifestations of COVID-19 and the adverse ophthalmic reactions related to its vaccinations., (Copyright © 2023 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Purpose: This study reviews evidence and provides recommendations for the ideal setting of intravitreal injection (IVI) administration of vascular endothelial growth factor (VEGF) inhibitors., Methods: A multi-step approach was employed, including content analysis of regulations and guidelines, a systematic literature review, and an international survey assessing perioperative complications and endophthalmitis incidence in relation to injection settings. The literature review searched PubMed and Cochrane databases from 2006 to 2022, focusing on studies reporting correlations between complications and treatment settings. The survey utilized a web-based questionnaire distributed to clinical sites and the international ophthalmic community, with data managed using electronic capture tools., Results: We reviewed regulations and guidelines from 23 countries across five continents, finding significant variation in IVI administration settings. In most countries, IVI is primarily administered in outpatient clean rooms (96%) or offices (39%), while in others, it is restricted to ambulatory surgery rooms or hospital-based operating theatres (4%). The literature review found that endophthalmitis risk after IVI is generally low (0.01% to 0.26% per procedure), with no significant difference between office-based and operating room settings. The international survey (20 centers, 96,624 anti-VEGF injections) found low overall incidences of severe perioperative systemic adverse events and endophthalmitis, independent of injection settings., Conclusion: No significant differences in perioperative complications were observed among various settings, including operating theatres, ambulatory surgery rooms, offices, hospitals, or extra-hospital environments. Choosing the appropriate clinical setting can optimize patient management, potentially increasing effectiveness, quality, productivity, and capacity., (© 2023. The Author(s).)

Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas, which are aggressive cancers associated with a poor outcome. Our review aims to explore the established standards of care for both types of tumors, highlight the emerging therapeutic strategies for OPG treatment, and propose potential alternative therapies that, while originally studied in a broader glioma context, may hold promise for OPGs pending further investigation. These potential therapies encompass immunotherapy approaches, molecular-targeted therapy, modulation of the tumor microenvironment, nanotechnologies, magnetic hyperthermia therapy, cyberKnife, cannabinoids, and the ketogenic diet. Restoring visual function is a significant challenge in cases where optic nerve damage has occurred due to the tumor or its therapeutic interventions. Numerous approaches, particularly those involving stem cells, are currently being investigated as potential facilitators of visual recovery in these patients.

We provide an overview of current macular imaging techniques and identify and describe biomarkers that may be of use in the routine management of macular diseases, particularly exudative age-related macular degeneration (AMD). This perspective includes sections on macular imaging techniques including optical coherence tomography (OCT) and OCT angiography (OCTA), classification of exudative AMD, and biomarkers in structural OCT and OCTA. Fluorescein angiography remains a vital tool for assessing the activity of neovascular lesions, while indocyanine green angiography is the preferred option for choroidal vessel imaging in neovascular AMD. OCT provides a non-invasive three-dimensional visualization of retinal architecture in vivo and is useful in the diagnosis of many imaging biomarkers of AMD-related neovascular lesions, including lesion activity. OCTA is a recent advance in OCT technology that allows accurate visualization of retinal and choroidal vascular flow. OCT and OCTA have led to an updated classification of exudative AMD lesions and provide several biomarkers that help to establish a diagnosis and the disease activity status of neovascular lesions. Individualization of therapy guided by OCT and OCTA biomarkers has the potential to further improve visual outcomes in exudative AMD. Moving forwards, integration of technologically-advanced imaging equipment with AI software will help ophthalmologists to provide patients with the best possible care., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Diabetes mellitus (DM) is one of the world's greatest health emergencies of the 21st century. Ocular complications of DM are commonly chronic and progressive, but vision loss can be effectively prevented or delayed with early detection and timely treatment. Therefore, regular comprehensive ophthalmologic examinations are mandatory. Ophthalmic screening and dedicated follow-up for adults with DM are well established, whereas, there is no consensus on optimal recommendations for the pediatric population, reflecting the lack of clarity about the current burden of disease in this age group., Objectives: To determine the epidemiology of ocular complications of diabetes and to assess optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) macular features in a pediatric population with DM. To review ophthalmological screening and follow-up plans for the diabetic pediatric population., Design: Observational study., Methods: Retrospective consecutive cohort study of all 165 diabetic patients (330 eyes) aged 0-18 years, examined between January 2006 and September 2018 at the Pediatric Department of 'S. Maria della Misericordia' Udine Hospital who underwent at least one complete ophthalmologic examination at the Ophthalmology University Clinic at the Udine Hospital. OCT and OCTA data were available for 37 patients (72 eyes, 2 excluded). The associations between ocular complications and selected potential risk factors were evaluated by univariate analyses., Results: No patient had signs of ocular diabetic complications or any macular morphological or micro-vascular impairment, regardless of any potential risk factor. The prevalence of strabismus and refractive errors in the study group, was found to be similar to non-diabetic pediatric populations., Conclusion: Screening and follow-up of ocular diabetic complications in children and adolescents could be performed less frequently than in adults with diabetes. There is no need to screen potentially treatable visual disorders in diabetic children earlier or more frequently than in the healthy children thus reducing time spent in hospital and permitting a better tolerance to medical examinations in diabetic pediatric patients. We described the OCT and OCTA patterns in a pediatric population with DM., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

Background: The effects of various dosages and treatment regimens on intravitreal aflibercept concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF were evaluated using a drug and disease assessment model. The 8 mg dosage received specific attention., Methods: A time-dependent mathematical model was developed and implemented using Wolfram Mathematica software v12.0. This model was used to obtain drug concentrations after multiple doses of different aflibercept dosages (0.5 mg, 2 mg, and 8 mg) and to estimate the time-dependent intravitreal free VEGF percentage levels. A series of fixed treatment regimens were modeled and evaluated as potential clinical applications., Results: The simulation results indicate that 8 mg aflibercept administered at a range of treatment intervals (between 12 and 15 weeks) would allow for the proportion of free VEGF to remain below threshold levels. Our analysis indicates that these protocols maintain the ratio of free VEGF below 0.001%., Conclusions: Fixed q12-q15 (every 12-15 weeks) 8 mg aflibercept regimens can produce adequate intravitreal VEGF inhibition.

Objective: We aimed to compare visual and anatomical outcome in vitrectomized and non-vitrectomized eyes treated with dexamethasone (DEX) implant due to diabetic macular oedema (DMO)., Design: Multicenter, retrospective, interventional study., Participants: 236 eyes from 234 patients with DMO with or without previous vitrectomy performed with follow-up of 12 months., Methods: Records were reviewed for cases of DMO treated with DEX implant in vitrectomized and not vitrectomized eyes. Best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) were recorded at baseline and 12 months after treatment with DEX implants. Correlations between vitreous status and visual and anatomical outcome, as well as safety profile were analysed., Main Outcome Measures: BCVA and CST over follow-up period., Secondary Outcomes: cataract rate formation, intraocular pressure increase, number of implants needed., Results: The non-vitrectomized group included 130 eyes (55.1%), the vitrectomized group included 106 eyes (44.9%). The groups were well balanced for age and gender (p = 0.540, and p = 0.053, respectively). Both groups showed statistically significant improvement in BCVA and CST (for all groups: p < 0.001). There was no significant difference between the groups in terms of change in vision (p = 0.89) and anatomy (p = 0.65). The mean number of DEX implants given during follow-up was 3.5 in both groups, and there was no significant difference between the groups (p = 0.81)., Conclusion: We demonstrated similar anatomical and functional efficacy of DEX implant in non-vitrectomized and vitrectomized eyes. Its efficacy was not influenced by full vitrectomy for diabetic retinopathy complications. Safety profile was well balanced between groups., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: A drug and disease assessment model was used to evaluate the impact of different treatment regimens on intravitreal ranibizumab, bevacizumab, aflibercept, and brolucizumab concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF., Methods: A time-dependent mathematical model using Wolfram Mathematica software was used. The pharmacokinetic and pharmacodynamic data for anti-VEGFs were obtained from published reports. The model simulated drug concentration after single and multiple doses of ranibizumab, bevacizumab, aflibercept, and brolucizumab, and it extrapolated time-dependent intraocular free VEGF proportion values. Various fixed treatment regimens (q4, q8, q10, q12) were simulated and evaluated as candidates for clinical utilization., Results: Our mathematical model shows good correlation between intraocular VEGF proportion values and clinical data. Simulations suggest that each anti-VEGF agent would allow for distinct treatment intervals to keep the proportion of free VEGF under threshold levels. Regimens scheduling q8 ranibizumab, q8 bevacizumab, q12 aflibercept, and q10 brolucizumab administration permit to maintain the proportion of unbound VEGF below 0.001%., Conclusions: Fixed q8 ranibizumab, q8 bevacizumab, q12 aflibercept, or q10 brolucizumab regimens may produce adequate intraocular VEGF inhibition.

The use of anti-vascular endothelial growth factor (VEGF) agents has profoundly changed the prognosis of neovascular age-related macular degeneration (nAMD). As clinical experiences have accumulated, it has become mandatory to summarize data to give information that can be useful in everyday practice. We conducted a systematic review to identify randomized controlled trials (RCTs) and observational studies that reported 12-month changes in best-corrected visual acuity (BCVA) in patients with nAMD on anti-VEGF monotherapy. Data were analyzed in a random-effects meta-analysis with BCVA change as the primary outcome. Meta-regression was conducted to evaluate the impact of multiple covariates. Four hundred and twelve heterogeneous study populations (109,666 eyes) were included. Anti-VEGFs induced an overall improvement of +5.37 ETDRS letters at 12 months. Meta-regression showed that mean BCVA change was statistically greater for RCTs ( p = 0.0032) in comparison with observational studies. Populations following a proactive regimen had better outcomes than those following a reactive treatment regimen. Mean BCVA change was greater in younger populations, with lower baseline BCVA and treated with a higher number of injections ( p < 0.001). Our results confirm that anti-VEGFs may produce a significant functional improvement at 12 months in patients with nAMD.