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Objective: to compare outcomes of cataract surgery combined with either anti-Vascular Endothelial Growth Factor (anti-VEGF) therapy or dexamethasone implant (DEX) in patients with diabetic macular oedema (DMO). Methods: Pubmed and Embase databases were searched for studies reporting outcomes of diabetic cataract surgery combined with either anti-VEGF or DEX, with a follow-up ≥3 months. The primary outcome was the mean change in central macular thickness (CMT). Mean change in best corrected visual acuity (BCVA) was considered as a secondary outcome. The mean difference between baseline and post-treatment values (MD) with 95%-Confidence Interval (95%CI) was calculated and meta-analyses were performed. Results: ninteen studies were included, 8 in the DEX group and 11 in the anti-VEGF group. A significant reduction of macular thickness was shown in the DEX group at 3 months (MD = −98.35 µm; 95% CI, −147.15/−49.54), while mean CMT change was non-significant in the anti-VEGF group (MD = −21.61 µm; 95% CI, −59.46/16.24; test of group differences, P < 0.001). At 3 months, no difference in visual gain was found between the two groups (P = 0.13). Conclusions: in DMO patients, cataract surgery combined with DEX seems to provide better anatomical outcomes compared with cataract surgery combined with anti-VEGF therapy. However, our evidence was limited by significant heterogeneity. Randomised trials comparing these two different combined approaches are warranted.

The aim of this study was to report on the anatomical and functional results of surgical management of seven cases of endophthalmitis related to a single day of intravitreal aflibercept injections. Patients with signs of endophthalmitis who underwent aflibercept injections (seven eyes) performed on the same day were retrospectively evaluated. The data of visual acuity and optical coherence tomography (OCT) within nine months of the follow-up and the treatment and results of microbiological cultures are reported. Four of the total seven cases had a positive bacterial culture outcome (Streptococcus mitis). All patients underwent vitrectomy combined with phacoemulsification when the eyes were not pseudophakic, vancomycin infusion, and silicone oil tamponade within 24 h, additionally, systemic antibiotics were administered intravenously. The final best-corrected visual acuity (BCVA) after the treatment was finger counting or light perception in all cases, and all eyes were saved with disruption of the inner retinal layers and stabilization of the retina in regard to changes related to the wet age-related macular degeneration (AMD). Although the retinal anatomy was mostly preserved, most of the patients affected by Streptococcus mitis-induced endophthalmitis did not regain baseline vision after the therapy.

PurposeTo investigate the vascular status of the macula in psoriasis patients without history of ocular inflammation by Optical Coherence Tomography Angiography (OCTA).MethodsThis prospective cross-sectional multicenter study included 55 psoriasis patients and 55 control healthy subjects. A complete eye examination and 6 mm × 6 mm OCTA imaging were performed. Retinal vascular status was evaluated by analyzing vascular density (VD) of superficial vascular plexus (superficial wVD) and deep vascular plexuses (deep wVD) in a 6 mm × 6 mm area and in foveal (superficial fVD and deep fVD) and parafoveal sectors (superficial pVD and deep pVD). In addition, foveal thickness (FT) and foveal avascular zone (FAZ) and clinical variables, including best corrected visual acuity (BCVA), intraocular pressure and refractive condition, were collected.ResultsBCVA, intraocular pressure and refractive condition were comparable between cases and controls. OCTA imaging showed that superficial wVD and superficial pVD were lower in the psoriasis group in comparison with controls (p = 0.009 and p = 0.01, respectively). Similarly, deep wVD and pVD were lower in the psoriasis group in comparison with control subjects (p = 0.03 and p = 0.01, respectively). In a sub-analysis of 47 patients affected by psoriasis without psoriatic arthritis, lower values of wVD and pVD in both superficial and deep capillary plexuses were registered.ConclusionOCTA is a useful tool which provides data on vascular status of the retina in psoriasis with no ocular involvement. VD data may suggest that vascular changes may occur earlier than clinical onset of posterior inflammation.

Purpose. To evaluate the efficacy of intravitreal dexamethasone implant (DEX) for the treatment of macular oedema secondary to vitrectomy for epiretinal membrane (ERM) and retinal detachment (RD) by conducting a systematic review with meta-analysis of published studies. Methods. Studies reporting clinical outcomes of DEX use for the treatment of macular oedema secondary to ERM and RD vitrectomy were searched on PubMed and Embase databases. The primary outcome was best-corrected visual acuity (BCVA) change between baseline and post-DEX treatment, reported as mean difference (MD) with 95% confidence interval (CI). Mean central macular thickness (CMT) change was assessed as a secondary outcome. Postimplant adverse events, including intraocular pressure rise and cataract development, were reported as well. Results. Five uncontrolled studies, 1 nonrandomized controlled study, and 1 randomized controlled study were included, with a total of 5 cohorts and 3 cohorts in the ERM group and RD group, respectively. Considering the last available follow-up, a significant improvement in postimplant BCVA was found in the overall population, irrespective of the indication for vitrectomy (MD = −0.28, 95% CI = −0.37, −0.20; p < 0.001 ), but with significant heterogeneity. In either group, mean BCVA significantly improved following the implant (in the ERM group, MD = −0.31, 95% CI = −0.40, −0.22; in the RD group, MD = −0.22, 95% CI = −0.41, −0.03), with no difference between the two groups ( p = 0.41 ). However, there was significant heterogeneity in both groups. Considering the last available follow-up, a significant CMT reduction was found in the overall population, irrespective of the indication for vitrectomy (MD = −129.75, 95% CI = −157.49, −102.01; p < 0.001 ). In the ERM group, a significant CMT reduction was shown following DEX (MD = −133.41, 95% CI = −155.37, −111.45; p < 0.001 ), with no heterogeneity. In the RD group, mean CMT reduction was borderline significant (MD = −128.37, 95% CI = −253.57, −3.18; p = 0.040 ), with significant heterogeneity. No difference in CMT improvement was found between the two groups ( p = 0.94 ). Conclusion. This meta-analysis showed that DEX yielded a significant improvement in visual and anatomical outcomes, even if limited by significant heterogeneity. Dexamethasone implant represents an effective treatment for postoperative macular oedema secondary to ERM and RD vitrectomy.

Purpose: To assess the incidence of normal vision following anatomically successful macular hole surgery and associated clinical variables. Methods: Multicentre, retrospective chart review. Preoperative, intraoperative and postoperative clinical data were extracted from electronic medical records from seven European vitreoretinal units. Inclusion criteria were as follows: eyes undergoing primary vitrectomy for idiopathic full-thickness macular hole from January 2015 to January 2018; postoperative macular hole closure confirmed by spectral domain optical coherence tomography (OCT); preoperative pseudophakia or phakic eyes receiving combined cataract surgery; one-year follow-up. The primary outcome was ‘normal vision’ defined as a final best-corrected visual acuity (BCVA) ≥ 20/25. Univariate, multivariate and decision-tree analyses were conducted to evaluate the clinical variables associated with ‘normal vision’. Odds ratios (OR) and confidence intervals (CIs) were calculated. Results: Of 327 eligible cases, 91 (27.8%) achieved ‘normal vision’ at 1year. Multivariate analysis identified variables significantly associated with ‘normal vision’: shorter symptom duration (odds ratio [OR]=1.05; 95% confidence interval [CI]:1.02-1.09; p=0.002), smaller preoperative OCT minimum linear diameter (OR per 100-micron increase=1.65; 95%CI:1.31-2.08; p&nbsp

The aim of the study is to evaluate the progression of visual field (VF) defects over 16 years of observation and to assess abnormalities in vessels and retinal nerve fibre layer (RNFL) thickness in patients with optic disc drusen (ODD). Both static automated perimetry (SAP) and semi-automated kinetic perimetry (SKP) were performed in 16 eyes of 8 patients (mean age 54 years) with ODD among 26 eyes of 13 patients examined 16 years before. The area of I2e, I4e, III4e, and V4e isopters was measured in deg2. The MD and PSD parameters were estimated using SAP. Optical coherence tomography angiography (OCT-A) was additionally performed in 16 ODD eyes and 16 eyes of 8 healthy subjects to estimate the RNFL thickness and vessel density of the optic nerve disc and the macula. The differences in all isopter areas of SKP and SAP parameters after 16 years were not significant. The analysis of OCT-A showed a significant reduction of the vessel density and RNFL of the peripapillary area in each segment in patients with ODD, compared with the control group. The highest reduction of RNFL was observed in the superior segment of the optic disc area (92.56μm vs 126.63μm) also the macular thickness was decreased in ODD patients, compared with the control group. In the macula, there was a significant vascular defect in the whole superficial layer and in the parafoveal deep layer. A strong significant correlation of the parafoveal deep plexus with MD and PSD parameters was detected. In conclusion, VF loss due to ODD after 16 years of the follow-up was not significant both in SKP and SAP. ODD caused a reduced vessel density and RNFL, as well as macular thickness in OCT-A. SAP parameters were influenced by parafoveal deep plexus.

Background: Cataract surgery is the most common operation performed worldwide. A fixed topical corticosteroid-antibiotic combination is usually prescribed in clinical practice for 2 or more weeks to treat post surgical inflammation and prevent infection. However, this protracted schedule may increase the incidence of corticosteroid-related adverse events and notably promote antibiotic resistance. Methods: This International, multicentre, randomized, blinded-assessor, parallel-group clinical study evaluated the non-inferiority of 1-week levofloxacin/dexamethasone eye drops, followed by 1-week dexamethasone alone, vs. 2-week gold-standard tobramycin/dexamethasone (one drop QID for all schedules) to prevent and treat ocular inflammation and prevent infection after uncomplicated cataract surgery. Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) around a treatment difference >–10%. The study randomized 808 patients enrolled in 53 centres (Italy, Germany, Spain and Russia). The primary endpoint was the proportion of patients without anterior chamber inflammation on day 15 defined as the end of treatment. Endophthalmitis was the key secondary endpoint. This study is registered with EudraCT code: 2018-000286-36. Results: After the end of treatment, 95.2% of the patients in the test arm vs. 94.9% of the control arm had no signs of inflammation in the anterior chamber (difference between proportions of patients = 0.028; 95% CI: −0.0275/0.0331). No case of endophthalmitis was reported. No statistically significant difference was evident in any of the other secondary endpoints. Both treatments were well tolerated. Conclusions: Non-inferiority of the new short pharmacological strategy was proven. One week of levofloxacin/dexamethasone prevents infection, ensures complete control of inflammation in almost all patients and may contain antibiotic resistance.

Purpose: To report clinical outcomes of two different timings of intravitreal dexamethasone (DEX) implant administration for prevention of diabetic macular oedema (DME) worsening following cataract surgery. Methods: This multicentre, retrospective study included patients with DME who received an intravitreal DEX implant 1month before cataract surgery, ‘precataract DEX’ group, or at the time of cataract surgery, ‘concomitant treatments’ group. Inclusion criteria were a follow-up ≥3months and ophthalmological examination with optical coherence tomography (OCT) imaging at baseline (cataract surgery) and throughout follow-up. Anatomical improvement was considered to be a decrease in OCT central subfield (CSF) thickness ≥20% compared to baseline. The primary outcomes were anatomical and functional results at 3months. Results: Two hundred twenty-one patients were included: 136 in the ‘precataract DEX’ group and 85 in the ‘concomitant treatments’ group. At 3months, a reduction of CSF thickness≥20% was found in 7.3% of eyes in the ‘precataract DEX group’ and in 83.7% of eyes in the ‘concomitant treatments’ group (p&nbsp

Purpose: To compare efficacy of treat and extend (T&E) versus fixed regimen treatment protocols in neovascular age-related macular degeneration (nAMD). Methods: 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. Results: 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 Conclusion: 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.

The treatment for rhegmatogenous retinal detachment (RRD) is surgery, including pars plana vitrectomy (PPV) and scleral buckling (SB). Despite surgical advances, degeneration of the photoreceptors and post-operative complications, such as proliferative vitreoretinopathy (PVR), often occurs as the result of inflammation, preventing complete visual recovery or causing RRD recurrence. There is increasing evidence that in the presence of RRD, the activation of inflammatory processes occurs and the surgery itself induces an inflammatory response. This comprehensive review focuses on the use of different formulations of corticosteroids (CCS), as an adjunctive treatment to surgery, either PPV or SB, for RRD repair. The purpose was to review the efficacy and safety of CCS in improving functional and anatomical outcomes and in preventing postoperative complications. This review is organized according to the timing of CCS administration: preoperative, intraoperative, and postoperative. The evidence reviewed supported the role of the pre-operative use of CCS in the treatment of combined RRD and choroidal detachment (CD), reducing CD height. No solid consensus exists on intraoperative and postoperative use of CCS to treat and prevent postoperative complications. However, a large randomized clinical trial including more than 200 eyes suggested that oral prednisone after surgery decreases the rate of postoperative grade B PVR.

Purpose: To compare the clinical outcomes and the rate of complications of 27-gauge transconjunctival nonvitrectomizing vitreous surgery (NVS) and of 25-gauge transconjunctival sutureless vitrectomy surgery for idiopathic epiretinal membrane removal. Methods: In this prospective randomized study, 83 phakic eyes of 83 consecutive patients with an idiopathic epiretinal membrane were randomized to receive 27-gauge NVS (NVS-group) or 25-gauge vitrectomy (Standard-group). Main outcome measures were best-corrected visual acuity, central retinal thickness, nuclear density units' changes, and rate of complications. Results: Thirty-nine eyes of the Standard-group and 40 of the NVS-group were considered in final analysis. Mean best-corrected visual acuity improved significantly in both groups, with a significant better result at 12 months in NVS-group (P 0.039; t-test). Central retinal thickness decreased significantly in both groups (P < 0.001, Tukey test), without significant difference between the two groups at any time point. At 12 months, nuclear density increased significantly in the Standard-group (analysis of variance, P < 0.001), and it did not change in the NVS-group (analysis of variance, P 0.537). Epiretinal membrane recurred in 5.1% of eyes in the Standard-group and in 7.5% of eyes in the NVS-group (Fisher's exact test, P 1.000). Conclusion: The 27-gauge NVS is an effective surgical procedure in eyes with epiretinal membrane and it induces less progression of nuclear sclerosis than 25-gauge vitrectomy.

Purpose. To evaluate the effects of a modification of the traditional 25-gauge pars plana vitrectomy technique in the treatment of uncomplicated macula-on rhegmatogenous retinal detachment (RRD) with intermediate retinal break(s) and marked vitreous traction in the phakic eye. Methods. Prospective, noncomparative, and interventional case series. All consecutive phakic eyes with primary uncomplicated macula-on RRD with intermediate retinal break(s) and marked vitreous traction, with at least 1 year of postoperative follow-up, were enrolled. In all eyes, “localized 25-gauge vitrectomy” under air infusion with localized removal of the vitreous surrounding the retinal break(s), in association with laser photocoagulation and air tamponade, was performed. The primary end point was the rate of primary retinal attachment. Secondary end points were cataract progression and assessed by digital Scheimpflug lens photography (mean change of nuclear density units) and the rate of complications. Results. Thirty-two phakic eyes were included in the final analysis. At 12 months, the primary outcome of anatomical success was achieved in 94% of eyes. The mean nuclear density units did not change significantly at any time point during the follow-up. After localized vitrectomy, one eye developed an epiretinal membrane, and one eye developed cystoid macular edema; no other significant complications were reported. Conclusions. “Localized vitrectomy” has a high anatomical success rate in phakic eyes with primary uncomplicated macula-on RRD with intermediate retinal break(s) and marked vitreous traction, without causing progression of cataract.

Yacoub A Yousef,1 Mona Mohammad,1 Ibrahim AlNawaiseh,1 Reem AlJabari,1 Mario Damiano Toro,2,3 Almutez Gharaibeh,4 Robert Rejdak,5 Katarzyna Nowomiejska,5 Sandrine Zweifel,3 Teresio Avitabile,6 Magdalena Rejdak,6 Rashed Nazzal2 1Department of Surgery (Ophthalmology), King Hussein Cancer Centre, Amman, Jordan; 2Faculty of Medical Sciences, Collegium Medicum, Cardinal Stefan Wyszy&nacute;ski University, Warsaw, Poland; 3Department of Ophthalmology, University of Zürich, Zürich, Switzerland; 4School of Medicine, The University of Jordan, Amman, Jordan; 5Department of General Ophthalmology, Medical University of Lublin, Lublin, Poland; 6Department of Ophthalmology, University of Catania, Catania, ItalyCorrespondence: Yacoub A YousefDepartment of Surgery (Ophthalmology), King Hussein Cancer Centre, Queen Rania St, Amman, 11941, JordanTel +96265355000Email yyousef@khcc.joMario Damiano ToroDepartment of Ophthalmology, University Hospital of Zürich, Raemistrasse 100, Zürich, 8091, SwitzerlandTel +39 3495158220Email toro.mario@email.itPurpose: Ciliary body (CB) and iris thicknesses may change with certain eye diseases as well as between different populations. Here, we report Ultrasound Biomicroscopy Measurements (UBM) of the normal thickness for the CB and the iris from a homogenous population in the Middle East.Patients and Methods: Sonomed 35-MHz (SONOMED, INC. New York, USA) images were obtained at 4 radial meridians, and the thickness was measured at 3 locations along the radial length of the iris and at the thickest part of the CB. Parameters included mean thickness, median thickness, range, and standard deviation.Results: Of 46 adult patients, 83 normal eyes were included in this analysis. The overall mean, median iris thicknesses at the iris root, midway along the radial length of the iris, and at the juxtapupillary margin in mm were 0.42, 0.41 ± 0.08, 0.52, 0.51± 0.08, and 0.72, 0.71± 0.1, respectively. The overall mean, median thicknesses of the CB and CB + ciliary processes in mm were 0.72, 0.71 ± 0.1, and 1.42, 1.37 ± 0.2 respectively. Gender, age, side, and height had no impact on iris and/or CB thickness (p> 0.05). However, the iris thickness was significantly thicker in the superior quadrant than inferiorly, and in the nasal quadrant than the temporal quadrant (p=0.04), and the CB thickness and the CB + ciliary processes thickness were significantly thicker in the superior quadrant than inferiorly (P = 0.04 and 0.02 consecutively).Conclusion: We measured in this study the normal thickness of the CB and the iris in normal eyes from homogenous population in the Middle East using ultrasound biomicroscopy. Our findings are essential for the ophthalmic community worldwide and in the Middle East region and can be used as a normative thickness data for the iris and CB in healthy eyes.Keywords: ultrasound biomicroscopy, iris, ciliary body

The objective of this prospective study was to investigate the morphological changes of myopic choroidal neovascularization (mCNV) after treatment with anti-vascular endothelial growth factor and to identify potential features predictive of the final BCVA. OCT and OCTA features were evaluated at baseline and at 1, 6 and 12 months. Parameters investigated were the maturity pattern, presence of mCNV OCT activity signs, subretinal fibrosis and mCNV area. Forty patients (41 eyes) were included in the study. At the final visit, after a mean of 3.1 ± 1.4 injections, BCVA had improved significantly (p = 0.009) and subretinal hyperreflective exudation, subretinal fluid and intraretinal cysts nearly disappeared at 12 months. At baseline, 20 eyes had an immature CNV that were smaller, required less injections (2.5 ± 1.2 vs 3.8 ± 1.4, p = 0.002), they completely regressed in seven eyes and achieved a better BCVA (0.14 ± 0.15 vs 0.40 ± 0.26 logMAR, p

Aim: To examine the effect of subthreshold micropulse yellow laser (SMYL) on best-corrected visual acuity (BCVA), central macular thickness (CMT), and optical coherence tomography angiography (OCT-A) changes in eyes with persistent diabetic macular edema (DME) after pars plana vitrectomy (PPV) for tractional DME (TDME).Patients and Methods: In a comparative study, 95 eyes of 95 consecutive patients with persistent DME were prospectively enrolled. The SMYL group (54 eyes) was treated with SMYL 6 months after PPV, while the control group (41 eyes) was followed up without treatment. BCVA and CMT by OCT were analyzed at baseline and 3 and 6 months. Additionally, parameters such as the vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), respectively, and the area of the foveal avascular zone (FAZ) were also evaluated on OCT-A.Results: There were no significant differences between both groups in demographic data. In the SMYL group, mean BCVA was significantly increased [F(2,106) = 17.25; p < 0.001; ηp2 = 0.246] from 51.54 ± 13.81 ETDRS letters at baseline to 57.81 ± 12.82 ETDRS letters at 3 months (p < 0.001) and 57.83 ± 13.95 EDTRS letters at 6 months (p < 0.001), respectively. In comparison to the control group, BCVA values were statistically significantly higher in the SMYL group at 3 and 6 months, respectively. Mean CMT significantly decreased [F(2,106) = 30.98; p < 0.001; ηp2 = 0.368] from the baseline value 410.59 ± 129.91 μm to 323.50 ± 89.66 μm at 3 months (p < 0.001) and to 283.39 ± 73.45 μm at 6 months (p < 0.001). CMT values were significantly lower in the SMYL group (p < 0.001), especially at 6 months follow-up time (p < 0.001) compared with the control group. Parafoveal VD in the SCP and DCP was significantly higher in the SMYL group in comparison to the control group, respectively, at 3-month (SCP p < 0.001; DCP p < 0.001) and 6-month follow-up (SCP p < 0.001; DCP p < 0.001). FAZ area was also significantly smaller in the SMYL group at 6-month follow-up (p = 0.001). There were no adverse SMYL treatment effects.Conclusion: SMYL therapy may be a safe and effective treatment option in eyes with persistent macular edema following PPV for TDME.

Background: The introduction of non-invasive diagnostic tools in ophthalmology has significantly reshaped current clinical practice in different settings. Recently, different anterior segment (AS) intraoperative optical coherence tomography (i-OCT) systems have been employed for different interventional procedures including cataract surgery. Materials and Methods: A review on the use of AS i-OCT in the management of cataract surgery, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence according to the Oxford Centre for Evidence-Based Medicine (OCEM) 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were assessed for all included articles. Results: Out of 6302 articles initially extracted, 6302 abstracts were identified for screening and 32 of these met the inclusion/exclusion criteria for full-text review; 19 articles were excluded. Conclusions: The use of AS i-OCT in cataract surgery, even if only a few studies have a high level or grade of evidence, may represent a useful tool for novel surgeons approaching phacoemulsification but also for expert ones for teaching purposes and to plan and manage complicated cases.

Topic: To investigate whether an increasing number of intravitreal anti-VEGF injections is associated with a higher mortality risk. Clinical Relevance: 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. Methods: 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. Results: 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). Conclusion: 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.