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 metaregression. 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. Metaregression 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

Infection control measures in ophthalmology during the COVID-19 outbreak: A narrative review from an early experience in Italy

Introduction: The novel coronavirus (SARS-CoV-2) is infecting people and spreading easily from person-to-person. Cases have been detected in most countries worldwide. Italy is one of the most affected countries as of 30 March 2020. Public health response includes a rapid reorganization of the Italian National Healthcare System in order to reduce transmission of COVID-19 within hospitals and healthcare facilities, while optimizing the assistance to patients with severe COVID-19 complications. Methods: We analysed the actions that were taken in three ophthalmology centres in northern Italy during the SARS-CoV-2 outbreak and how these measures affected patient\u2019s attendance. In addition, due to the rapidly evolving scenario, we reviewed the evidence available during the course of this pandemic. Results: A full reorganization of ophthalmology services is mandatory according to current existing infection containment measures in order to continue dispensing urgent procedures without endangering the community with amplification of the diffusion chain. Ophthalmologists are considered at elevated risk of exposure when caring patients and vice versa, due to their close proximity during eye examination. High volumes of procedures typically generated by ophthalmologists with concurrent implications on the risk of infection are considered when re-assessing healthcare facilities reorganization. Conclusion: Containment measures in the event of pandemic due to infective agents should be well known by healthcare professionals and promptly applied in order to mitigate the risk of nosocomial transmission and outbreak

Scleral fixation of a single-piece foldable acrylic IOL through a 1.80 mm corneal incision

A new scleral fixation technique of a single-piece acrylic foldable intraocular lens (IOL) (enVista MX60, Bausch & Lomb, Inc.) through a 1.80 mm corneal incision, using the IOL eyelets as anchoring point, is described. It was a retrospective review of 26 cases. The preoperative mean corrected distance visual acuity was 0.51 \ub1 0.21 logarithm of the minimum angle of resolution (logMAR). It improved significantly to 0.25 \ub1 0.27 logMAR (P < .01), 0.18 \ub1 0.16 logMAR (P < .01), and 0.17 \ub1 0.16 logMAR (P < .01) (at 1 month, 3 months, and 6 months postoperatively, respectively, repeated measures analysis of variance, P < .0001). No astigmatism increase of more than 0.75 diopters was recorded at any time point. In all 26 patients, the IOL was well centered and stable for the entire monitoring period. No complications were observed during follow-up. Scleral fixation of the foldable IOL through a 1.80 mm corneal incision provided excellent IOL stability during the 6-month follow-up of this study and might be an effective and safe surgical technique

Color fundus autofluorescence to determine activity of macular neovascularization in age-related macular degeneration

Purpose: To evaluate with color fundus autofluorescence (FAF) different lesion components of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) and to assess its activity. Methods: In total, 137 eyes (102 patients) with MNV underwent a complete eye exami-nation, including color fundus photography, optical coherence tomography (OCT), OCT angiography, and confocal color FAF, with an excitation wavelength at 450 nm. Each image was imported into a custom-image analysis software for quantitative estimation of emission wavelength and green and red emission fluorescence (GEFC/REFC) inten-sity, considering both single components of neovascular AMD and different MNV types (type 1 and type 2 MNV, active and inactive MNV). Results: Subretinal fluid (SRF) had significantly higher values of GEFC (P = 0.008 and P = 0.0004) and REFC intensity (P = 0.005 and P = 0.0003) versus fibrosis and atrophy. The emission wavelength from SRF was lower compared to atrophy (P = 0.024) but not to fibrosis (P = 0.46). No significant differences were detected between type 1 and 2 MNV. Considering active versus inactive MNVs, a difference was detected for all evaluated parameters (P < 0.001). Mean FAF wavelength of both MNV with SRF and intrareti-nal fluid (IRF) was lower versus inactive MNV (P < 0.001 and P = 0.005). MNV with SRF (P < 0.001) had higher values of GEFC and REFC versus inactive MNV (P < 0.001). MNV with IRF had higher values of GEFC versus inactive MNV (P = 0.05). Conclusions: Quantitative color FAF can differentiate active versus inactive MNV, whereas no differences were found between type 1 and type 2 MNV. If these data can be further confirmed, color FAF may be useful for automatic detection of active MNV in AMD and as a guide for treatment. Translational Relevance: Automatic quantitative evaluation of green and red emission components of FAF in AMD can help determine the activity of MNV and guide the treatment

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

Triple therapy for anti-vascular endothelial growth factor nonresponders in neovascular age-related macular degeneration: Impact of different photodynamic therapy parameters

Purpose: To evaluate the safety and exploratory efficacy of triple therapy (TT) with single-session intravitreal ranibizumab, modified juxtascleral triamcinolone, and photodynamic therapy (PDT) in exudative age-related macular degeneration non-responder to anti-vascular endothelial growth factor. Methods: Thirty consecutive eyes were included. The first 10 eyes (cohort 1) enrolled received same-day TT with reduced-fluence/reduced-irradiance PDT, 10 eyes (cohort 2) received same-day TT with reduced-fluence/standard irradiance PDT, the last 10 eyes (cohort 3) received same-day TT with standard fluence/standard irradiance PDT. Results: All patients completed the 6-month follow-up. Mean best corrected visual acuity (BCVA) at baseline was 1.1 (cohort 1), 0.9 (cohort 2) and 1.1 (cohort 3) logMAR. After 6 months, mean BCVA change was-0.15 (not significant),-0.13 (not significant) and 0.29 (p < 0.05) logMAR, respectively. Among eyes treated with standard fluence/standard irradiance PDT, 2 showed choroidal ischemia. Conclusions: The combination of modified juxtascleral triamcinolone, reduced-fluence PDT, and ranibizumab appears as a safe treatment option. \ua9 2013 S. Karger AG, Basel