Purpose: To assess the effect of topical antibiotic prophylaxis on postoperative endophthalmitis after intravitreal injection of anti–vascular endothelial growth factor agents. Methods: A systematic literature search was performed from inception to March 2016 using PubMed, Medline, Web of Science, Embase, and the Cochrane Library, to identify articles that reported cases of endophthalmitis after intravitreal injection of anti–vascular endothelial growth factor agents. We used a pooled analysis to estimate the incidence of cases of endophthalmitis who developed after injections performed with and without topical antibiotic prophylaxis. We used regression analysis to explore the effects of study characteristics on heterogeneity. Results: From our search of electronic databases, we identified and screened 4,561 unique records. We judged 60 articles to have reported findings for cohorts of patients who met our inclusion criteria, (12 arms of randomized clinical trials, 11 prospective cohort studies, and 37 retrospective cohort studies), which included 244 cases of endophthalmitis and 639,391 intravitreal injections of anti–vascular endothelial growth factor agents. The final pooled estimate endophthalmitis proportions were 9/10,000 (95% confidence interval, 7/10,000–12/10,000) in the antibiotic-treated group and 3/10,000 (95% confidence interval, 2/10,000–5/10,000) in the untreated group. The estimated incidence of endophthalmitis with topical antibiotic prophylaxis was approximated three times the incidence without prophylaxis. Random effects regression showed that none of the study characteristics significantly affected the effect size in either group. Conclusion: Topical antibiotic after intravitreal injection of anti–vascular endothelial growth factor agents is associated with a higher risk of endophthalmitis.

Ocular bacterial infections represent a serious problem that affecting people of all age and genders. These infections can lead to visual impairment and blindness if not properly treated. The current study evaluates the antimicrobial resistance profiles and the resistance trend of both Staphylococcus aureus (S. aureus) and coagulase-negative staphylococci (CoNS), the main pathogens involved in eye infections. A total of 322 isolates of S. aureus and CoNS, were collected from patients with bacterial conjunctivitis and keratitis at the “Luigi Vanvitelli” University Hospital of Campania in Naples, Italy, between 2017 and 2020. The isolated bacteria showed a high percentage of resistance to methicillin and other antibiotics commonly used for the treatment of ocular infections. Trends in antibiotic resistance were not encouraging, recording—especially among CoNS strains—an increase of more than 20% in resistance to methicillin and aminoglycosides during the study period. Instead, the resistance rates to tetracycline had a significant decrease in CoNS isolates while no changes in their susceptibility to fluoroquinolones and macrolides were observed. However, all isolates showed no resistance to trimethoprim/sulfamethoxazole and chloramphenicol. In this scenario, preventive identification of the infection causative agents and the evaluation of the antimicrobial susceptibility patterns are essential to set up an ocular infection effective drug treatment and also prevent antibiotic resistance.

Purpose: To assess the efficacy of vitrectomy in degenerative and tractional lamellar macular holes (LMHs) by meta-analysis of published studies. Methods: PubMed, Medline and Embase databases were searched up to May 2020. Included cohorts were divided into three groups: degenerative LMH group, lamellar hole associated epiretinal proliferation (LHEP) group and tractional LMH group. LHEP is likely to be associated with degenerative LMHs, but less commonly could be associated with mixed LMHs. To reduce risk of possible misclassification bias, eyes with LHEP which could not have been precisely classified by the authors, were included into the LHEP group. The primary outcome was to investigate the visual change following primary vitrectomy in the degenerative LMH and LHEP group versus the tractional LMH group. A sensitivity analysis excluding the LHEP group was also performed on the primary outcome. Mean difference (MD) in best corrected visual acuity between baseline and post-treatment was calculated, along with 95% confidence interval (CI). Rate of incidence of post-operative full-thickness macular hole (FTMH) was assessed as secondary outcome. Results: Thirteen studies were included. Pooled analyses including all groups showed a significant visual improvement following vitrectomy (pre-post MD = -0.17;95%CI = -0.22,-0.12;p<0.001), with no difference in visual improvement between the degenerative LMH and LHEP group and the tractional LMH group. The sensitivity analysis excluding LHEP group confirmed no difference in visual change between the degenerative LMH group (pre-post MD = -0.18;95%CI = -0.24,-0.12;p<0.001) and the tractional LMH group (MD = -0.16;95%CI = -0.26,-0.07;p<0.001). The incidence rate of post-operative FTMH was higher in the degenerative LMH and LHEP group than in the tractional LMH group (p = 0.002). Conclusion: Primary vitrectomy for LMH ensured a favorable visual outcome, with no difference in visual gain between degenerative and tractional LMHs. However, a higher incidence of post-operative FTMHs was found in eyes with the degenerative LMH subtype.

To investigate whether an increasing number of intravitreal anti-VEGF injections is associated with a higher mortality risk. The issue of systemic safety of intravitreal anti-VEGF therapy has been long discussed. Evidence from meta-analyses of randomized studies has shown no increased risk of mortality in the overall population, whereas some warning signals of higher mortality were found in patients with diabetes exposed to intense and prolonged treatment. Concerns have been raised about whether an increasing number of anti-VEGF injections could be associated with a higher mortality. Randomized clinical trials enrolling arms with different intensities of anti-VEGF therapy were searched. The primary outcome measure was the incidence rate ratio (IRR) of death with 95% confidence interval (CI) for receiving 5 injections. The relationship between the number of injections and all-cause mortality was investigated. Separate regression analyses were conducted to investigate this relationship in subgroups of studies with different diseases and drugs. Fifty-two trials were included. Overall mortality rates of 1.02% and 3.36% were recorded at 12 and 24 months, respectively. Univariate regression showed that a larger number of injections was not associated with a significant increase in mortality both at 12 months (IRR, 1.16; 95% CI, 0.87-1.53; P = 0.31) and at 24 months (IRR, 1.05; 95% CI, 0.95-1.15; P = 0.34). According to subgroup analyses, in diabetic macular edema (DME) studies, a higher risk was marginally associated with an increasing number of injections at 24 months (IRR, 1.17; 95% CI, 1.02-1.33; P = 0.03). No significant influence of anti-VEGF treatment intensity on mortality was shown, supporting a message of reassurance over safety concerns of this therapy. Marginal evidence of a higher risk associated with a more intense treatment was found in patients with DME.

Intravitreal therapy with anti–vascular endothelial growth factor (VEGF) agents represents the most remarkable breakthrough in treatment of many retinal diseases during the last 25 years, with 7 million estimated intravitreal injections in the United States and more than 20 million throughout the world in 2016.¹ Despite outstanding clinical efficacy, some concerns have been raised about the safety profile of these agents.^2,3 No risk of systemic adverse events, including mortality rate, has been found in randomized clinical trials (RCTs) that evaluated the safety profile of anti-VEGF drugs.^4-9 However, assessing the risk of mortality associated with intravitreal anti-VEGF therapy is challenging, because no registered trial, to our knowledge, has been sufficiently powered to detect a significant difference between anti-VEGF treatment and control groups owing to the low incidence of the event.¹⁰ Furthermore, an increased mortality rate recently has been reported after intravitreal anti-VEGF treatment in the general population¹¹ and patients presenting additional risk factors.^12,13 Systematic reviews and meta-analyses published on this issue reported controversial outcomes.^2,3,14

To compare efficacy of treat and extend (T&E) versus fixed regimen treatment protocols in neovascular age-related macular degeneration (nAMD). Randomized clinical trials (RCTs) comparing T&E versus fixed regimen protocols for nAMD were systematically searched. Primary outcome was to compare the mean best corrected visual acuity (BCVA) change in T&E regimen versus fixed regimen. Secondary outcomes were change in the mean optical coherence tomography (OCT) central retinal thickness (CRT) and mean number of injections. Standardized mean difference (SMD) along with 95% confidence intervals (CIs) were calculated. Random-effect models were used for meta-analyses. Four RCTs were included, with a total of 649 and 621 eyes in the T&E and fixed regimen cohort at 12 months, and 267 and 249 eyes at 24 months. Pooled analysis of mean BCVA change included all four RCTs at 12 months and two RCTs at 24 months, showing no difference between the two groups (12-month: SMD = 0.08, 95% CI: −0.20 to 0.35, p = 0.55; 24-month: SMD = 0.04, 95% CI: −0.13 to 0.21, p = 0.64). Pooled analysis of OCT CRT change at 12 months included three studies, showing no difference between the two groups (SMD = 0.03, 95% CI: −0.46 to 0.51, p = 0.91). Pooled analysis of mean injection number included all four RCTs at 12 months and two RCTs at 24 months, showing significant difference between the two groups (12-month: SMD = −1.11, 95% CI: −1.67 to −0.56, p < 0.001; 24-month: SMD = −1.34, 95% CI: −1.54 to −1.15, p < 0.001). A T&E regimen proved as effective as a fixed dosage regimen throughout a 24-month follow-up and with a lower number of injections.