Francesca Menchini

A Systematic Review of Endophthalmitis after Microincisional versus 20-Gauge Vitrectomy

BACKGROUND Endophthalmitis is a rare but severe complication of vitrectomy. CLINICAL RELEVANCE Post-surgical endophthalmitis is suspected to be more frequent after microincisional (23- and 25-gauge) compared with standard (20-gauge) vitrectomy. METHODS We conducted a systematic review of studies that compared microincisional and standard vitrectomy by searching MEDLINE and EMBASE up to November 2012. We used the Bayesian meta-analysis method to compute the odds ratio (OR) of endophthalmitis. We conducted subgroup analyses to compare the effect of different incision types and use of perioperative antibiotics. RESULTS We identified 3 small randomized and 18 nonrandomized studies that reported 68 cases of endophthalmitis in 148 643 participants. The overall OR of endophthalmitis for microincisional versus standard vitrectomy was 2.3 (95% credible interval [CrI], 0.8-5.8). We found an increased risk of endophthalmitis using a microincisional straight approach compared with standard vitrectomy (OR, 15.1; 95% CrI, 2.01-179), but not for a beveled approach (OR, 0.82; 95% CrI, 0.23-2.28). The OR of studies that reported on mixed microincision was between these 2 values (OR, 4.4; 95% CrI, 1.32-14.3). We estimated that the overall rate of endophthalmitis with 20-gauge vitrectomy was 3 cases in 10 000 procedures, and the probability that a beveled microincision increases the rate of endophthalmitis to more than 6 or 9 events was small (no more than 5% or 1%, respectively). CONCLUSIONS We did not find an increased risk of endophthalmitis for microincisional vitrectomy compared with standard vitrectomy. The beveled approach seems to be safer than a straight approach, supporting the current recommendation of its adoption in microincisional vitrectomy. However, these findings must be interpreted cautiously because of the small number of endophthalmitis events reported from included studies.

Reproducibility of Macular Thickness Measurements Using Cirrus SD-OCT in Neovascular Age-Related Macular Degeneration

PURPOSE To assess the test-retest variability of central and sectorial macular thickness measurements obtained by Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) in neovascular age-related macular degeneration (nAMD). METHODS Macular thickness measurements of nine standard ETDRS subfields were obtained and analyzed. The repeatability of macular thickness measurements by Cirrus HD-OCT was assessed by examining the intrasession within subject standard deviation (Sw), coefficient of repeatability (CR), and coefficient of variation (CV), before and after eyes with retinal segmentation errors were excluded. RESULTS Forty-nine nAMD eyes of 49 consecutive patients were included in the study. The CR for the central macular subfield was 42.4 microm (10.5%) and ranged from 12.1 microm (3.7%) for the outer nasal to 41.8 microm (11.4%) for the inner nasal subfields. In a secondary analysis, eyes affected by erroneous detection of inner and outer retinal boundaries (6/49, 12.24%) were excluded. The revised coefficient of repeatability for the central macular subfield was 26.1 microm (8.1%) and ranged from 10.3 microm (3.8%) for the outer superior to 30.2 microm (8.3%) for the inner nasal subfields. CONCLUSIONS Overall, the test-retest variability of Cirrus HD-OCT is good for the central and sectorial macular subfields, with a low incidence of scan artifacts.

Intravitreal bevacizumab versus ranibizumab for the treatment of retinal angiomatous proliferation

Purpose:  To evaluate the effects of intravitreal bevacizumab and ranibizumab treatments in retinal angiomatous proliferation (RAP).

Bilateral Simultaneous Nonarteritic Anterior Ischemic Optic Neuropathy after Ingestion of Sildenafil for Erectile Dysfunction

Purpose. To describe a patient who developed bilateral, simultaneous nonarteritic anterior ischemic optic neuropathy (NAION) after ingestion of Sildenafil citrate (Viagra) for erectile dysfunction. Methods. Observational case report. Results. A 60-year-old diabetic man noted sudden decrease of vision in both eyes 16 hours after his third consecutive 50 mg daily Sildenafil ingestion. A diagnosis of bilateral NAION was made and he was treated for three days with methylprednisolone 1 g/d intravenously, followed by oral prednisone 75 mg/d. Final visual acuity was 20/50 right eye (OD) and 20/20 left eye (OS). He had preexisting diabetes. Conclusion. This is the first reported case of simultaneous bilateral NAION occurred in a diabetic patient early after Sildenafil intake. Patients with predisposing conditions such as diabetes have to be warned against the use of PDE inhibitors.

Effects of VEGF inhibition on retinal morphology, neovascular network size, and visual acuity in patients with vascularized pigment epithelium detachment because of occult choroidal neovascularization.

Purpose: To report the results of vascular endothelial growth factor inhibition for vascularized pigment epithelium detachment associated with choroidal neovascularization secondary to age-related macular degeneration. Methods: We performed a retrospective analysis of patients affected by vascularized pigment epithelium detachment treated with intravitreal anti–vascular endothelial growth factor (0.5 mg of ranibizumab or 1 mg of bevacizumab) and a follow-up of 12 months. Retinal angiomatous proliferations were excluded. Treatment was conducted with an initial loading phase followed by a pro re nata phase. Fluorescein angiography and indocyanine green angiography were performed at baseline and every 3 months. Results: Forty eyes were included in this study. After a follow-up of 12 months and 5.5 treatments on average, best-corrected visual acuity did not vary significantly. Central retinal thickness and pigment epithelium detachment height were significantly reduced, whereas the choroidal neovascularization area remained constant. Conclusion: In vascularized pigment epithelium detachment, anti–vascular endothelial growth factor therapy shows visual stabilization but not best-corrected visual acuity gain. However, it is associated with significant morphologic improvements, and it may offer a benefit over the natural course of the disease.

Diabetic macular edema: correlations with available diabetes therapies--evidence across a qualitative review of published literature from MEDLINE and EMBASE.

Diabetic macular edema (DME) is the leading cause of visual loss and legal blindness in people with diabetes mellitus. The pathogenesis of DME is complex and multifactorial, and involves both local and systemic risk factors that may alter the blood-retina barrier and allow leakage of protein and fluid into the macula. Recently, in addition to well known risk factors, the use of thiazolidinediones (glitazones) has been related to the development and worsening of DME. This review is based on available literature derived from EMBASE and MEDLINE, from 1950 to May 2010, and focuses on the potential correlations between DME and current available therapies for type 1 and 2 diabetes.This review reveals that the current literature, with the potential exception of glitazones, is not sufficient for a definite statement on the association between DME and currently available diabetic therapies. In fact, among antidiabetic agents, the class of glitazones appears the only one to be potentially associated with DME. Furthermore, adequately powered, prospective studies are warranted to evaluate the exact causal association between glitazones and DME and to exclude the role of other confounding factors potentially able to induce or exacerbate macular edema. Improvement of the quality and reporting in postmarketing surveillance and the use of the ‘dechallenge and rechallenge’ approach in case of suspicious cause/effect drug relationship of DME are highly encouraged.

Pharmacological Treatments for Neovascular Age-Related Macular Degeneration: Can Mixed Treatment Comparison Meta-Analysis be Useful?

OBJECTIVE To investigated the use of mixed treatment comparison (MTC) meta-analysis models to summarize results from randomized clinical trials (RCTs) on approved pharmacological treatments for neovascular age-related macular degeneration (AMD). METHODS The number of patients with visual loss or visual gain of 3 or more lines of visual acuity (15 ETDRS letters) at 1 year was extracted from 10 RCTs including patients with neovascular AMD and comparing at least one of the following drugs to sham treatment (1080 control patients, 8 studies) or to each other: verteporfin photodynamic therapy (PDT, 1124 patients, 4 studies), pegaptanib (904 patients, 2 twin studies), ranibizumab (984 patients, 4 studies). Both frequentist and Bayesian methods were used to conduct MTCs. RESULTS Direct and indirect evidence was available and found to be overall in good agreement for the comparisons: PDT vs. control, ranibizumab vs. control, ranibizumab vs. PDT. Bayesian model fit was better for a model including a covariate coding for the PIER study ranibizumab regimen, i.e. quarterly injections after three initial monthly doses. In the MTC model, monthly ranibizumab was superior to PDT and pegaptanib, and could not be shown to be better than PIER ranibizumab regarding visual loss, being estimates imprecise. Ranibizumab PIER retreatment regimen was better than PDT and pegaptanib regarding visual loss, whereas an advantage over them regarding visual gain was suggested by a frequentist MTC approach, but not by a Bayesian approach, which was more conservative. A limitation of our MTC model was that only two twin studies connected pegaptanib to the treatment network, and only one study was available for the PIER ranibizumab regimen. CONCLUSION The clinically heterogeneous and sparse typology of the evidence is a limitation to carry out MTC meta-analyses of approved pharmacological treatments for neovascular AMD. Ranibizumab was found to be the most effective treatment compared to PDT and pegaptanib, although this superiority cannot be demonstrated regarding visual gain for the PIER ranibizumab regimen in a Bayesian analytic setting. We did not find RCTs which investigated the current ranibizumab as needed retreatment regimen approved in Europe.

Cost–effectiveness of treatments for diabetic macular oedema: should we pay more attention to the appraisal and reporting of economic evaluations?

Diabetic macular oedema (DMO) is a major cause of visual loss among diabetics, occurring in 14% to 25% of patients depending on age and insulin treatment status.1 In 2006, the International Diabetes Federation showed that diabetes affects 246 million people worldwide—a figure that will rise to 552 million by 2030 (http://www.idf.org/diabetesatlas/5e/theglobal-burden); therefore the burden of care for DMO will be massive worldwide. Antiangiogenic therapy is an established treatment option in patients with macular oedema due to diabetic retinopathy. A recently published Cochrane review2 has summarised the evidence, showing that intravitreal injections of vascular endothelial growth factor inhibitors can achieve better visual outcomes at 1 year than conventional focal or grid laser photocoagulation. The cost–effectiveness of this treatment, however, has been questioned in the last few years, particularly in the UK where the National Institute for Health and Care Excellence (NICE) has been using sophisticated methods informing cost utility assessment (see http://www.nicedsu.org.uk/). The Cochrane review found that at 1 year, antiangiogenic therapy can at least double the chance of gaining three or more lines of vision, as well as halve the risk of losing them. This evidence was collected by meta-analysis of 2 studies on bevacizumab (167 participants), 2 on ranibizumab (300 participants) and 1 on aflibercept (221 participants, of whom 89 were used in the analysis). The evidence was judged to be of moderate quality, mainly because there were not enough trials to investigate heterogeneity and the overall sample size did not meet optimal criteria for sample size requirements.2 Better evidence was available for ranibizumab, but there was little power to investigate the difference in drug efficacy. Safety of the drug and the intravitreal injection procedure was good in the trials, but further long-term data are believed to be needed to exclude …

Antibiotic prophylaxis for preventing endophthalmitis after intravitreal injection: a systematic review

PurposeTo assess the effect of topical antibiotic prophylaxis on the rate of post-operative endophthalmitis after intravitreal injection (IVI).MethodsWe conducted a systematic review of studies comparing the rates of endophthalmitis in eyes receiving IVI of different drugs with and without topical antibiotic prophylaxis, by searching MEDLINE and EMBASE up to June 2016. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool and the Risk Of Bias in Non-randomized Studies of Interventions (ROBINS-I) for randomized clinical trials (RCTs) and non-randomized studies, respectively. We used a random-effects meta-analysis to compute the odds ratio (OR) of endophthalmitis with antibiotic prophylaxis compared with no prophylaxis and conducted subgroup analyses to compare the efficacy of different regimens and classes of antibiotics on endophthalmitis rates.ResultsWe identified 1 randomized and 12 non-randomized studies that reported 74 cases of endophthalmitis in 147,203 IVIs using antibiotic prophylaxis compared with 55 cases in 211,418 IVIs with no prophylaxis. The overall OR of endophthalmitis for antibiotic prophylaxis vs. no prophylaxis was 1.33 (95% CI 0.75–2.38). Leave-one-out sensitivity analyses showed that the exclusion of the only study with a serious risk of bias significantly increased the risk of endophthalmitis in the antibiotic prophylaxis group compared with control (OR: 1.62, 95% CI: 1.17, 2.34). There was no difference in the endophthalmitis rate associated with any other factor analyzed, including type of antibiotic, type of drug injected, or antibiotic prophylaxis regimen.ConclusionsAntibiotic prophylaxis does not reduce the rate of endophthalmitis following IVI and might potentially be associated with an increased risk of post-operative infection.

OCT vs. Photography or Biomicroscopy for Diagnosis of Diabetic Macular Edema

Diabetic macular edema (DME) was defined in Early Treatment Diabetic Retinopathy Study (ETDRS) studies on the basis of central retinal thickening and hard exudates using fundus stereophotography or biomicroscopy (FP/FB). Clinically significant macular edema (CSME) is the more severe form of DME and needs to be treated. Compared with FP/FB, optical coherence tomography (OCT) provides imaging of retinal thickness and morphology, as well as of the vitreoretinal interface. Clinical examination using FP/FB is cheap and readily available, but is also a subjective method. When biomicroscopy is used, there is no recording of the amount of thickening, and thus, it cannot reliably monitor CSME except for a gross judgment on its presence or absence. Advantages of OCT when compared with FP/FB in patients with DME are its ability to obtain an objective and highly reliable quantitative measure of retinal thickness on a continuous scale, as well as to provide additional morphological details. Clinician suspecting CSME requiring treatment can use Stratus central subfield thickness values below 250 μm to rule out CSME, and values above 300 μm to rule in CSME. Thickness values between 250 and 300 μm still suggest CSME, but treatment decision should be based, even more than usual, on patient’s symptoms and preferences as well as on other clinical features that an ophthalmologist may use to decide on potential treatment outcome. Add 50 μm to the thresholds suggested above when using Cirrus (and possibly other spectral domain) OCT (no CSME: below 300 μm; CSME: above 350 μm); confirmatory research is needed on this correction factor for each spectral-domain device. Retinal-thickness measurement should not be a surrogate for visual acuity measurement in patients with DME. OCT-based predictors of outcome after photocoagulation, vitrectomy, and intravitreal triamcinolone have been proposed, and the prognosis of cases with subclinical macular edema (i.e., thickening using OCT not found using FP/FB) have been studied in case series and need further investigation. Using Stratus OCT, a change in the central subfield thickness exceeding ±11% is likely to represent a true change in a subject if the quality of the scans is acceptable. The repeatability of spectral-domain OCTs is expected to be comparable or better than that of the Stratus OCT in patients with DME, but further research is needed.