Behind the mask: a critical perspective on the ethical, moral, and legal implications of AI in ophthalmology.

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.

Submacular hemorrhage during neovascular age-related macular degeneration: a meta-analysis and meta-regression on the use of tPA and anti-VEGFs.

BACKGROUND: Submacular hemorrhage (SMH) associated with neovascular age-related macular degeneration (nAMD) precipitates rapid visual decline and impacts quality of life. Treatments vary, but combined recombinant tissue plasminogen activator (tPA) and anti-vascular endothelial growth factor (anti-VEGF) therapy has gained prominence as a viable treatment option. OBJECTIVES: This study aims to evaluate the efficacy of the combination of tPA and anti-VEGF. METHODS: We conducted a systematic review meta-analysis following PRISMA guidelines, focusing on studies examining tPA and anti-VEGF therapy in SMH secondary to nAMD. Outcomes measured were change in best-corrected visual acuity (BCVA) and success rate of SMH displacement. Meta-regression assessed the relative efficacy of intravitreal and subretinal delivery. RESULTS: Out of 257 initial reports, 22 studies involving 29 patient populations met inclusion criteria. Our analysis showed significant improvement in BCVA and a high rate of successful SMH displacement with combined tPA and anti-VEGF therapy. No significant differences were found between subretinal and intravitreal tPA administration. Furthermore, when evaluating the effects of subretinal versus intravitreal anti-VEGF administration in patients treated with subretinal tPA, the results indicated similar efficacy. CONCLUSIONS: Combined tPA and anti-VEGF therapy is effective in managing SMH in nAMD patients, significantly improving visual acuity and SMH displacement. The location of tPA and anti-VEGF delivery did not significantly impact outcomes.

The ideal intravitreal injection setting: office, ambulatory surgery room or operating theatre? A narrative review and international survey.

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.

Automated diabetic retinopathy detection with two different retinal imaging devices using artificial intelligence: a comparison study.

PURPOSE: In this study, we evaluated the diagnostic performance of an automated artificial intelligence-based diabetic retinopathy (DR) algorithm with two retinal imaging systems using two different technologies: a conventional flash fundus camera and a white LED confocal scanner. METHODS: On the same day, patients underwent dilated colour fundus photography using both a conventional flash fundus camera (TRC-NW8, Topcon Corporation, Tokyo, Japan) and a fully automated white LED confocal scanner (Eidon, Centervue, Padova, Italy). All images were analysed for DR severity both by retina specialists and the AI software EyeArt (Eyenuk Inc., Los Angeles, CA) and graded as referable DR (RDR) or not RDR. Sensitivity, specificity and the area under the curve (AUC) were computed. RESULTS: A series of 165 diabetic subjects (330 eyes) were enrolled. The automated algorithm achieved 90.8% sensitivity with 75.3% specificity on images acquired with the conventional fundus camera and 94.1% sensitivity with 86.8% specificity on images obtained from the white LED confocal scanner. The difference between AUC was 0.0737 (p = 0.0023). CONCLUSION: The automated image analysis software is well suited to work with different imaging technologies. It achieved a better diagnostic performance when the white LED confocal scanner is used. Further evaluation in the context of screening campaigns is needed.

TWELVE-MONTH OUTCOMES OF INTRAVITREAL AFLIBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Fixed Versus As-needed Dosing.

PURPOSE: To compare the clinical outcomes of aflibercept used with a fixed schedule with a pro-re-nata (PRN) retreatment regimen in patients affected by neovascular age-related macular degeneration. METHODS: This is a prospective multicenter, noninferiority, propensity score-matched study evaluating the 12-month outcomes of aflibercept given either according to labeling or following a PRN regimen. Patients included in the latter group received one initial injection, followed by monthly visits and as-needed retreatment. RESULTS: One-to-one matching resulted in fixed and PRN arms containing 92 eyes each. Visual acuity improved from baseline to 12 months in both the study groups. At Month 4, the fixed regimen was equivalent to the PRN regimen (mean difference: 1.75 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: -1.42 to +4.92). The pro-re-nata regimen failed to show noninferiority compared with the fixed regimen at both Month 8 (mean difference: 3.43 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: +0.25 to +6.22) and Month 12 (mean difference: 4.83 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: +1.37 to +8.29). All patients in the fixed group received seven injections. Patients included in the PRN arm received a mean of 5.5 ± 1.6 treatments. CONCLUSIONS: Aflibercept given with a fixed treatment regimen produces better visual acuity outcomes than an individualized regimen.

A comparison between a white LED confocal imaging system and a conventional flash fundus camera using chromaticity analysis.

BACKGROUND: Conventional flash fundus cameras capture color images that are oversaturated in the red channel and washed out in the green and blue channels, resulting in a retinal picture that often looks flat and reddish. A white LED confocal device was recently introduced to provide a high-quality retinal image with enhanced color fidelity. In this study, we aimed to evaluate the color rendering properties of the white LED confocal system and compare them to those of a conventional flash fundus camera through chromaticity analysis. METHODS: A white LED confocal device (Eidon, Centervue, Padova, Italy) and a traditional flash fundus camera (TRC-NW8, Topcon Corporation, Tokyo, Japan) were used to capture fundus images. Color images were evaluated with respect to chromaticity. Analysis was performed according to the image color signature. The color signature of an image was defined as the distribution of its pixels in the rgb chromaticity space. The descriptors used for the analysis are the average and variability of the barycenter positions, the average of the variability and the number of unique colors (NUC) of all signatures. RESULTS: Two hundred thirty-three color photographs were acquired with each retinal camera. The images acquired by the confocal white LED device demonstrated an average barycenter position (rgb = [0.448, 0.328, 0.224]) closer to the center of the chromaticity space, while the conventional fundus camera provides images with a clear shift toward red at the expense of the blue and green channels (rgb = [0.574, 0.278, 0.148] (p < 0.001). The variability of the barycenter positions was higher in the white LED confocal system than in the conventional fundus camera. The average variability of the distributions was higher (0.003 ± 0.007, p < 0.001) in the Eidon images compared to the Topcon camera, indicating a greater richness of color. The NUC percentage was higher for the white LED confocal device than for the conventional flash fundus camera (0.071% versus 0.025%, p < 0.001). CONCLUSIONS: Eidon provides more-balanced color images, with a wider richness of color content, compared to a conventional flash fundus camera. The overall higher chromaticity of Eidon may provide benefits in terms of discriminative power and diagnostic accuracy.

Early Effects of Dexamethasone Implant on Macular Morphology and Visual Function in Patients with Diabetic Macular Edema.

PURPOSE: To evaluate the early effects of dexamethasone implant in patients with diabetic macular edema (DME). METHODS: Eyes with DME were prospectively included in the study. 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: Twenty-three eyes of 20 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 469 µm after 1 day (p < 0.05), and 275 µm (p < 0.01) at the end of the follow-up. BCVA gain (p < 0.0001, repeated measures ANOVA) was on average +2 ETDRS letters at day 1 (not significant), +9 letters from day 28 to day 90 (p < 0.01). CONCLUSION: Intravitreal dexamethasone implant showed an early and fast effect in reducing CRT and improving BCVA in DME patients.

Intravitreal bevacizumab for choroidal neovascularization due to pathologic myopia: long-term outcomes.

PURPOSE: To report the long-term results of anti-vascular endothelial growth factor (VEGF) therapy for choroidal neovascularization (CNV) secondary to pathological myopia (PM). METHODS: Prospective interventional study with extension phase. Eyes affected by CNV due to PM included. All patients received an intravitreal bevacizumab injection (1.25 mg/0.05 ml) at baseline. Re-treatment was considered at each follow-up visit. RESULTS: The study included 101 consecutive eyes of 86 patients. All patients reached 24 months of follow-up. After 24 months, mean best-corrected visual acuity (BCVA) improvement was -0.13 (95 % CI: -0.2; -0.05) logMAR (p < 0.001) and central retinal thickness (CRT) decreased on average by 67 (95 % CI: 27; 102) µm (p < 0.01). The chorioretinal atrophy (CRA) area increased significantly after 2 years of follow-up (+7.82 mm(2), p < 0.0001). Patients received 4.1 treatments, on average. Thirty-two eyes were included in the extension phase (from 24 to 60 months of follow-up). Visual acuity improved on average by -0.05 (95 % CI: -0.2; 0.1) logMAR (p > 0.05) compared to baseline. Mean reduction in CRT was 102 (95 % CI: 64;141) µm (p < 0.01). The CRA area enlarged significantly after 5 years of follow-up (+14.15 mm(2), p < 0.0001). Patients received a mean of 6.7 treatments in 60 months. CONCLUSIONS: An individualized regimen with intravitreal bevacizumab to treat CNV secondary to PM resulted in BCVA improvement and CRT decrease at 2 and 5 years. The main visual benefit was obtained between month 3 and month 24. A gradual loss of the initial BCVA gain was observed starting from month 30 to month 60 due to progression of CRA.

INTRAVITREAL AFLIBERCEPT FOR CHOROIDAL NEOVASCULARIZATION DUE TO AGE-RELATED MACULAR DEGENERATION UNRESPONSIVE TO RANIBIZUMAB THERAPY.

PURPOSE: To assess the efficacy of intravitreal injection of aflibercept for treating choroidal neovascularization due to age-related macular degeneration unresponsive to ranibizumab. METHODS: Prospective noncomparative study. Indication for conversion to aflibercept (2.0 mg) was a failed response to ranibizumab, defined as persistent or recurrent subretinal and/or intraretinal fluid on spectral domain optical coherence tomography. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score), fluorescein angiography, indocyanine green angiography, and spectral domain optical coherence tomography were performed at baseline. Patients were followed up monthly, and retreatment was considered at physician discretion based on functional and morphological patterns. RESULTS: Ninety-two eyes were included in the study. At 12 months, mean best-corrected visual acuity (±SD) change was +1.8 (±10.3), Early Treatment Diabetic Retinopathy Study letters and central retinal thickness (±SD) decreased on average by 112 (±173) µm. Patients received a mean of 3.5 ± 1.8 injections. No significant adverse event was observed during the follow-up. CONCLUSION: A low number of intravitreal aflibercept injections reversed the preswitching trend toward losing vision and produced stable visual acuity and morphological improvements for up to 12 months in patients with neovascular age-related macular degeneration, not responding to ranibizumab.

Intravitreal steroids for the treatment of retinal diseases.

Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events.

Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose.

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.

Explainable artificial intelligence model for the detection of geographic atrophy using colour retinal photographs.

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.

The Present and Future of Optic Pathway Glioma Therapy.

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.

Vitrectomized vs non-vitrectomized eyes in DEX implant treatment for DMO-Is there any difference? the VITDEX study.

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.

Update on coronavirus disease 2019: Ophthalmic Manifestations and Adverse Reactions to Vaccination.

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.

Biosimilars for retinal diseases: United States-Europe awareness survey (Bio-USER - survey).

PURPOSE: To assess the awareness of biosimilar intravitreal anti-VEGF agents among retina specialists practicing in the United States (US) and Europe. METHODS: A 16-question online survey was created in English and distributed between Dec 01, 2021 and Jan 31, 2022. A total of 112 respondents (retinal physicians) from the US and Europe participated. RESULTS: The majority of the physicians (56.3%) were familiar with anti-VEGF biosimilars. A significant number of physicians needed more information (18.75%) and real world data (25%) before switching to a biosimilar. About one half of the physicians were concerned about biosimilar safety (50%), efficacy (58.9 %), immunogenicity (50%), and their efficacy with extrapolated indications (67.8 %). Retinal physicians from the US were less inclined to shift from off-label bevacizumab to biosimilar ranibizumab or on-label bevacizumab (if approved) compared to physicians from Europe (p=0.0001). Furthermore, physicians from the US were more concerned about biosimilar safety (p=0.0371) and efficacy compared to Europe (p= 0.0078). CONCLUSIONS: The Bio-USER survey revealed that while the majority of retinal physicians need additional information regarding the safety, efficacy and immunogenicity when making clinical decisions regarding their use. Retinal physicians from US are more comfortable in continuing to use off-label bevacizumab compared to physicians from Europe.

Neovascular age-related macular degeneration.

PURPOSE: Neovascular age-related macular degeneration (AMD) is a leading cause of blindness, with an increasing incidence as the elderly population expands. Large, multi-center, randomized, clinical trials have been conducted exploring the safety and efficacy of anti-VEGF treatments. This paper aims to discuss the safety and efficacy of pegaptanib, ranibizumab, aflibercept and bevacizumab. New therapeutic agents and treatment strategies are also discussed. PROCEDURES: Evidence available from prospective, multicenter, clinical studies and from a selective literature search is utilized to present the results of VEGF inhibition in neovascular AMD and to generate evidence-based recommendations. RESULTS: Anti-VEGF treatment is indicated in choroidal neovascularization with active disease and produces a significant benefit in visual acuity. CONCLUSIONS: With the advent of anti-VEGF therapy, the prognosis of choroidal neovascularization has changed dramatically. Data from well-conducted clinical trials suggest that approved anti-VEGF drugs are effective and well tolerated.

Anti-VEGF Drugs Dynamics: Relevance for Clinical Practice.

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.

Managing Neovascular Age-Related Macular Degeneration in Clinical Practice: Systematic Review, Meta-Analysis, and Meta-Regression.

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.

Managing Diabetic Macular Edema in Clinical Practice: Systematic Review and Meta-Analysis of Current Strategies and Treatment Options.

PURPOSE: 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.