Chirag P. Shah

Aflibercept for exudative AMD with persistent fluid on ranibizumab and/or bevacizumab

Objective To investigate the effect of aflibercept 2.0 mg in cases resistant to ranibizumab 0.5 mg and/or bevacizumab 1.25 mg treatment. Purpose To evaluate the anatomic and visual effect of intravitreal aflibercept 2.0 mg in cases of exudative age-related macular degeneration (AMD) with persistent fluid on optical coherence tomography (OCT) despite regular ranibizumab 0.5 mg and/or bevacizumab 1.25 mg treatment at 1 and 6 months. Methods Retrospective review at Ophthalmic Consultants of Boston, Boston, Massachusetts, USA of exudative AMD cases with persistent fluid on regular ranibizumab 0.5 mg and/or bevacizumab 1.25 mg treatment switched to intravitreal aflibercept 2.0 mg treatment and followed for 6 months. Tabulated data included details of prior treatments, best available visual acuity, central subfoveal thickness on registered spectral domain OCT before and after aflibercept injection centred on the anatomic fovea and macular description before and after aflibercept injection. Results A total of 353 eyes with exudative AMD were switched to aflibercept during the study period. Of these, 28 eyes in 28 patients had persistent fluid after an average of 20 regular ranibizumab/bevacizumab injections (range 7–37). At 1 month, 89% (25 eyes) showed anatomic improvement and 18% (five eyes) were dry after a single aflibercept injection. Central subfoveal thickness improved from 295 to 272 microns (p<0.001) after one aflibercept injection. After an average of 4.4 aflibercept injections (range 3–6) over 6 months, the central subfoveal thickness remained improved (274 microns, p=0.008); 64% (18 eyes) showed anatomic improvement and a quarter of eyes (25%, seven eyes) were dry. Visual acuity did not improve at 1 month (logarithm of minimum angle of resolution (logMAR) 0.54, Snellen 20/69, p=0.64) or 6 months (logMAR 0.57, Snellen 20/76, p=0.49). Treatment was well tolerated with no adverse events reported. Conclusions A significant proportion of exudative AMD cases with persistent fluid on OCT despite regular ranibizumab 0.5 mg and/or bevacizumab 1.25 mg treatment respond anatomically to aflibercept 2.0 mg. Visual acuity did not improve. Aflibercept may be beneficial anatomically in cases of exudative AMD treated with persistent fluid on ranibizumab and/or bevacizumab.

Outcomes and Risk Factors Associated with Endophthalmitis after Intravitreal Injection of Anti- Vascular Endothelial Growth Factor Agents.

OBJECTIVE To describe outcomes of and risk factors for endophthalmitis after intravitreal anti-vascular endothelial growth factor (VEGF) injection. DESIGN Single-center, consecutive, case series and retrospective case-control study. PARTICIPANTS Between January 1, 2009, and May 31, 2010, 16 vitreoretinal surgeons administered a total of 27 736 injections. During this period, 23 cases of presumed infectious endophthalmitis occurred. Each surgeon used his own preferred injection technique. INTERVENTION Vitreous or aqueous tap, or both, with intravitreal antibiotic injection and subsequent topical antibiotic and steroid drops. MAIN OUTCOME MEASURES Visual acuity, bladed lid speculum use, conjunctival displacement, hemisphere of injection, bevacizumab versus ranibizumab, and infectious organism. RESULTS Seven of 23 cases had positive culture results; 3 grew coagulase-negative Staphylococcus. All cases had pain and vitritis on average 3.4 days (range, 1-6 days) after injection, with no difference between culture-positive and culture-negative groups. Eighteen (78%) of 23 cases had a hypopyon. Fifteen of 23 cases returned to baseline vision (±2 lines) within 3 months. Neither lid speculum use (0.10% vs. 0.066% in the no-use group; P = 0.27), conjunctival displacement (0.11% vs. 0.076% in the no-displacement group; P = 0.43), hemisphere of injection (0.11% superior vs. 0.079% inferior; P = 0.56), or bevacizumab versus ranibizumab (0.11% vs. 0.066%; P = 0.21) affected risk. Analysis of only culture-positive results yielded similar results. There was no statistically significant difference between the proportion of culture-negative cases after bevacizumab injection (83%) versus ranibizumab injection (55%; P = 0.13). CONCLUSIONS Most patients in whom presumed infectious endophthalmitis develop after anti-VEGF injection regained baseline vision after treatment. Bladed lid speculum use, conjunctival displacement, hemisphere of injection, and type of anti-VEGF agent did not affect risk. No difference in culture-negative endophthalmitis rates was detected after bevacizumab versus ranibizumab injection. Neither the presence of pain, vitritis, decreased vision, hypopyon, nor the interval between injection and development of symptoms differentiate culture-positive from culture-negative cases. Because a subgroup of patients had poor outcomes, a low threshold for vitreous tap with intravitreal antibiotic injection may be warranted. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Treatment of Acute Retinal Necrosis

OBJECTIVES To compare outcomes from patients with acute retinal necrosis (ARN) treated in the acyclovir-only era with those treated in the era of newer antiviral therapies, identify variables affecting outcomes in ARN, and evaluate strategies for fellow eye prophylaxis. DESIGN Multicenter, nonrandomized, retrospective, interventional series. PARTICIPANTS A cohort of 58 patients diagnosed with ARN by a retina specialist at 1 of 4 referral centers between 1981 and 2008. The cohort was divided into 2 subgroups: patients treated during the acyclovir-only era (n = 36) and patients treated during the current era of newer antiviral medications (n = 22). INTERVENTION Intravenous, oral, or intravitreal antiviral medications, including acyclovir, valacyclovir, famciclovir, valganciclovir, ganciclovir, and foscarnet; prophylactic laser retinopexy; aspirin; oral steroids. MAIN OUTCOME MEASURES Visual acuity, retinal detachment, and fellow eye involvement. RESULTS A wide range and combination of antiviral agents are currently used for initial and long-term treatment of ARN. Outcomes from the newer antivirals era were similar to those achieved during the acyclovir-only era. In both groups, the incidence of 20/200 or worse visual acuity was 24% per person-year (P = 0.91). The prevalence of retinal detachment was approximately 50% in each group (P = 0.59). No variables, including prophylactic laser retinopexy, were associated with risk of retinal detachment. Two patients (3.4%) developed ARN in the initially unaffected eye. CONCLUSIONS Current treatment trends vary widely, including single agents or combinations of oral, intravenous, and intravitreal agents. Differing strategies did not affect outcomes. The final visual acuity in ARN was generally poor. Retinal detachment was common and could neither be predicted nor prevented. Development of ARN in the unaffected fellow eye occurred rarely. Long-term oral antiviral treatment strategies varied with unclear relative efficacy. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Changes in Antibiotic Resistance Patterns of Conjunctival Flora Due to Repeated Use of Topical Antibiotics after Intravitreal Injection

OBJECTIVE To determine the effect of repeated intermittent use of topical antibiotics after intravitreal injections on conjunctival bacterial flora and antibiotic resistance. DESIGN Cross-sectional case-control study. PARTICIPANTS AND CONTROLS A total of 80 eyes of 40 patients were enrolled (40 study eyes, 40 control eyes). Patients were enrolled with unilateral exudative age-related macular degeneration who had received at least 3 prior intravitreal injections with use of postinjection topical antibiotics. Patients had received an average of 7 (range, 3-13) intravitreal injections before enrollment. METHODS At the time of enrollment, the inferior fornix of the treated eye was swept with a culture swab before use of povidone iodine; the inferior fornix of the fellow eye was also cultured and served as a control. The culture and sensitivity data from the study and control eyes were analyzed. MAIN OUTCOME MEASURES The rate of antibiotic resistance among the conjunctival bacterial flora of the study eyes and control eyes. RESULTS A total of 80 eyes of 40 patients were enrolled in the study; 29 patients used trimethoprim/polymyxin B drops, and 11 patients used fluoroquinolone drops after each injection. A total of 58 bacterial colonies were isolated from 50 eyes. There were no significant differences in bacterial species or culture positivity rates between study and control eyes. Coagulase-negative staphylococcus accounted for 41 of the 58 bacterial colonies (71%). There was a 63.6% resistance rate to fluoroquinolones among study eyes compared with 32.1% among control eyes (P < 0.05). In the subset of 11 study eyes using fluoroquinolone drops for 4 days after injection, there was an 87.5% resistance rate compared with 25.0% in matched control eyes (P = 0.04). There was no significant difference in trimethoprim resistance rates between study and control eyes: Four of 14 study eyes (28.6%) showed resistance compared with 5 of 18 control eyes (27.7%) (P = 1.0). CONCLUSIONS Use of fluoroquinolone drops after intravitreal injection leads to increased rates of resistance among conjunctival flora. Repeated use of topical fluoroquinolones after intravitreal injections may have a detrimental effect on eye health by breeding resistance in the bacterial flora.

Ocular candidiasis: a review

Aims: To review the epidemiology, diagnosis and changing treatment paradigm of ocular candidiasis, and report current prevalence rates and risk factors at one inpatient hospital. Design: Retrospective review; systematic literature review. Methods: All Wills Eye Institute inpatient ophthalmology consultations from Thomas Jefferson University Hospital were retrospectively reviewed between June 2006 and November 2006. All consultations for candidaemia were included. The outcome variables included chorioretinitis, endophthalmitis, visual symptoms and Candida speciation. The ophthalmic literature was reviewed using PubMed. Keywords included Candida, candidaemia, chorioretinitis, vitritis and endophthalmitis. Bibliographies were manually searched. Results: Three of the 38 consultations for candidaemia (7.9%) had chorioretinitis. There were no cases of vitritis or endophthalmitis. The presence of symptoms, or the inability to articulate symptoms, was significantly associated with risk of ocular candidiasis (p = 0.003). All three cases of chorioretinitis had positive blood cultures for Candida albicans (p = 0.089) and were treated with oral fluconazole. Conclusions: Various factors have led to the increasing prevalence of inpatient candidaemia. Risk factors for ocular involvement include albicans species and the presence of, or inability to articulate, visual symptoms. For those without abnormal findings on initial examination, a subsequent retinal examination should be performed in 2 weeks, particularly if new symptoms develop or if the patient is unable to relay symptoms. Patients with chorioretinitis should be treated with systemic antifungal agents. For those with vitritis or endophthalmitis, particularly if worsening on systemic therapy alone, intravitreal antifungal medications or early vitrectomy should be considered.

Short-term outcomes of 25-gauge vitrectomy with silicone oil for repair of complicated retinal detachment.

Purpose: To investigate the short-term outcomes of 25-gauge pars plana vitrectomy (PPV) in 18 cases of complicated retinal detachment requiring silicone oil tamponade. Methods: In this retrospective noncomparative review, the primary outcome measures included postoperative anatomical status, preoperative and postoperative visual acuity and intraocular pressure (IOP), cataract progression, development of keratopathy, and other complications. The average follow-up was 5 months (142 days). Results: Thirteen (72.2%) of 18 patients had attachment postoperatively. There was no difference between preoperative visual acuity and visual acuity at the end of follow-up (P = 0.851). One patient (5.6%) who underwent concomitant penetrating keratoplasty had hypotony (IOP, <6 mmHg) postoperatively and until the end of follow-up. Ocular hypertension in two patients was controlled with antiglaucoma drops. Five (55.6%) of 9 patients who were initially phakic underwent cataract extraction or had documented cataract progression. There were no cases of keratopathy or endophthalmitis. Four patients had intraocular or retinal hemorrhage. Two patients developed significant macular epiretinal membranes, and one developed a parafoveal hole. Conclusions: Sutureless 25-gauge PPV with silicone oil is a relatively safe and comparable alternative to 20-gauge PPV with silicone oil for repair of complicated retinal detachment.

The Association of Cutaneous and Iris Nevi with Uveal Melanoma: A Meta-analysis

PURPOSE To study the relationship between cutaneous and iris nevi with uveal melanoma. DESIGN Meta-analysis. METHODS Three researchers independently searched the literature using Medline from 1966 to August 2007 (with both Ovid and PubMed), EMBASE, MD Consult, and the Web of Science. All bibliographies were searched, and an attempt to contact all primary authors was made to find further unpublished studies. MAIN OUTCOME MEASURES Risk factor data were extracted into 4 a priori groups: (1) atypical cutaneous nevi, (2) common cutaneous nevi, (3) cutaneous freckles, and (4) iris nevi. RESULTS Meta-analysis of 4 studies (850 cases) examining atypical cutaneous nevi yielded a summary odds ratio (OR) of 2.82 (95% confidence interval [CI], 1.10-7.26; P=0.032). Common cutaneous nevi were reported in 4 studies (825 cases), yielding a summary OR of 1.74 (CI, 1.27-2.39; P=0.001). Cutaneous freckles using 7 studies (2122 cases) found an OR of 1.22 (CI, 1.03-1.45; P=0.022). Iris nevi using 4 studies (825 cases) found an OR of 1.53 (CI, 1.03-2.27; P=0.036). There was no evidence of publication bias for the aforementioned risk factors, with the exception of atypical cutaneous nevi (P=0.03). CONCLUSIONS This meta-analysis supports an association between uveal melanoma and atypical cutaneous nevi, common cutaneous nevi, cutaneous freckles, and iris nevi.

Rapid Grading of Fundus Photographs for Diabetic Retinopathy Using Crowdsourcing

Background Screening for diabetic retinopathy is both effective and cost-effective, but rates of screening compliance remain suboptimal. As screening improves, new methods to deal with screening data may help reduce the human resource needs. Crowdsourcing has been used in many contexts to harness distributed human intelligence for the completion of small tasks including image categorization. Objective Our goal was to develop and validate a novel method for fundus photograph grading. Methods An interface for fundus photo classification was developed for the Amazon Mechanical Turk crowdsourcing platform. We posted 19 expert-graded images for grading by Turkers, with 10 repetitions per photo for an initial proof-of-concept (Phase I). Turkers were paid US

Early effect of tidal volume on lung injury biomarkers in surgical patients with healthy lungs.

0.10 per image. In Phase II, one prototypical image from each of the four grading categories received 500 unique Turker interpretations. Fifty draws of 1-50 Turkers were then used to estimate the variance in accuracy derived from randomly drawn samples of increasing crowd size to determine the minimum number of Turkers needed to produce valid results. In Phase III, the interface was modified to attempt to improve Turker grading. Results Across 230 grading instances in the normal versus abnormal arm of Phase I, 187 images (81.3%) were correctly classified by Turkers. Average time to grade each image was 25 seconds, including time to review training images. With the addition of grading categories, time to grade each image increased and percentage of images graded correctly decreased. In Phase II, area under the curve (AUC) of the receiver-operator characteristic (ROC) indicated that sensitivity and specificity were maximized after 7 graders for ratings of normal versus abnormal (AUC=0.98) but was significantly reduced (AUC=0.63) when Turkers were asked to specify the level of severity. With improvements to the interface in Phase III, correctly classified images by the mean Turker grade in four-category grading increased to a maximum of 52.6% (10/19 images) from 26.3% (5/19 images). Throughout all trials, 100% sensitivity for normal versus abnormal was maintained. Conclusions With minimal training, the Amazon Mechanical Turk workforce can rapidly and correctly categorize fundus photos of diabetic patients as normal or abnormal, though further refinement of the methodology is needed to improve Turker ratings of the degree of retinopathy. Images were interpreted for a total cost of US

Noninfectious Inflammation After Intravitreal Injection of Aflibercept: Clinical Characteristics and Visual Outcomes

1.10 per eye. Crowdsourcing may offer a novel and inexpensive means to reduce the skilled grader burden and increase screening for diabetic retinopathy.