Lyndell Lim

Natural history of central retinal vein occlusion: an evidence-based systematic review.

OBJECTIVE To describe the natural history of central retinal vein occlusion (CRVO) based on the best available evidence from the literature. CLINICAL RELEVANCE Central retinal vein occlusion is a common sight-threatening retinal vascular disease. Despite the introduction of new interventions, the natural history of CRVO is unclear. METHODS Systemic review of all English language articles retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008. This was supplemented by hand-searching references of review articles published within the last 5 years. Two investigators independently identified all relevant observational studies evaluating the natural history of RVO and all clinical trials evaluating interventions for CRVO; an untreated control arm was included. RESULTS Of 5966 citations retrieved, 53 studies were reviewed, providing 3271 eyes with CRVO for analysis of its natural history. Visual acuity (VA) was generally poor at baseline (<20/40) and decreased further over time. Although 6 studies reported an improvement in VA, none of these improvements resulted in VA better than 20/40. Up to 34% of eyes with nonischemic CRVO converted to ischemic CRVO over a 3-year period. In ischemic CRVO cases, neovascular glaucoma developed in at least 23% of eyes within 15 months. In nonischemic CRVO cases, macular edema resolved in approximately 30% of eyes over time, and subsequent neovascular glaucoma was rare. CONCLUSIONS Untreated eyes with CRVO generally had poor VA, which declined further over time. One quarter of eyes with nonischemic CRVO converted to ischemic CRVO.

Biologic therapies for inflammatory eye disease

The era of biologic medical therapies provides new options for patients with treatment‐resistant inflammatory eye disease. In this review, the authors summarize current published experience in a rapidly progressing clinical field, including the use of biologics, such as the tumour necrosis factor blockers, daclizumab and rituximab, and related agents, interferons and intravenous immunoglobulin, for the treatment of uveitis, scleritis and orbital inflammation. Reports of dramatic recoveries in patients with recalcitrant ocular inflammation who have received such therapies must be balanced against the high cost of biologics and the potential for serious, and at times unanticipated, complications of this treatment.

A Randomized Clinical Trial of Intravitreal Bevacizumab versus Intravitreal Dexamethasone for Diabetic Macular Edema: The BEVORDEX Study

OBJECTIVE To report the 12-month results of the first head-to-head comparison of a dexamethasone implant (Ozurdex; Allergan, Inc., Irvine, CA) versus bevacizumab (Avastin; Genentech, South San Francisco, CA) for center-involving diabetic macular edema (DME). DESIGN Phase 2, prospective, multicenter, randomized, single-masked clinical trial (clinicaltrials.gov identifier NCT01298076). PARTICIPANTS We enrolled 88 eyes of 61 patients with center-involving DME. METHODS Forty-two eyes were randomized to receive bevacizumab every 4 weeks and 46 eyes were randomized to receive a dexamethasone implant every 16 weeks, both pro re nata. Results were analyzed using linear regression with generalized estimation equation methods to account for between-eye correlation. MAIN OUTCOME MEASURES The primary outcome was the proportion of eyes that improved vision by 10 logarithm of minimum angle of resolution letters. Secondary outcomes included mean change in best-corrected visual acuity (BCVA), change in central macular thickness (CMT), injection frequency, and adverse events. Patient-reported outcomes were measured using the Impact of Vision Impairment (IVI) questionnaire. RESULTS Improvement in BCVA of 10 or more letters was found in 17 of 42 eyes (40%) treated with bevacizumab compared with 19 of 46 dexamethasone implant-treated eyes (41%; P = 0.83). None of the 42 bevacizumab eyes lost 10 letters or more, whereas 5 of 46 (11%) dexamethasone implant eyes did, mostly because of cataract. Mean CMT decreased by 122 μm for bevacizumab eyes and by 187 μm for dexamethasone implant eyes (P = 0.015). Bevacizumab-treated eyes received a mean of 8.6 injections compared with 2.7 injections for dexamethasone implant eyes. Significant improvement in IVI scores occurred for both treatment groups. CONCLUSIONS Dexamethasone implant achieved similar rates of visual acuity improvement compared with bevacizumab for DME, with superior anatomic outcomes and fewer injections. Both treatments were associated with improvement in visual quality-of-life scores. However, more dexamethasone implant-treated eyes lost vision, mainly because of cataract.

Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 18-Month Results of the Phase 3 GALILEO Study

PURPOSE To evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO). DESIGN Randomized, double-masked, phase 3 study. METHODS A total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks; the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The primary endpoint (proportion of patients who gained ≥15 letters) was at week 24. This study reports exploratory outcomes at week 76. RESULTS The proportion of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week 24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last observation carried forward; P < .001). Mean μm change from baseline central retinal thickness was -448.6 vs -169.3 at week 24 (P < .0001), -423.5 vs -219.3 at week 52 (P < .0001), and -389.4 vs -306.4 at week 76 (P = .1122). Over 76 weeks, the most common ocular serious adverse event in the intravitreal aflibercept group was macular edema (3.8%). CONCLUSIONS The visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when treatment intervals were extended. Patients with macular edema following CRVO benefited from early treatment with intravitreal aflibercept.

Prevalence and risk factors of retinal vein occlusion in an Asian population

Aim: To describe the prevalence and risk factors of retinal vein occlusion (RVO) in an Asian population. Methods: The Singapore Malay Eye Study is a population-based, cross-sectional study of 3280 (78.7%) Malay adults (aged 40–80 years) living in Singapore. All participants underwent retinal photography, standardised interview, clinical examinations and laboratory investigations. RVO (central or branch) was graded based on the Blue Mountains Eye Study (BMES) protocol from retinal photographs. Results: The overall prevalence of RVO was 0.7% (n = 22) (95% CI 0.4 to 1.0) (18 branch and five central RVO cases). There was no significant gender difference in RVO prevalence. RVO was associated with higher systolic blood pressure (age-adjusted odds ratio (OR) per SD increase 1.54, CI 1.02 to 2.31), ocular perfusion pressure (OR per SD increase 1.49, CI 1.03 to 2.16), a history of angina (OR 5.18, CI 1.49 to 18.0) and heart attack (OR 4.26, CI 1.47 to 12.3), and higher total cholesterol (OR per SD increase 1.55, CI 1.07 to 2.24) and LDL (OR per SD increase 1.47, CI 1.02 to 2.12) cholesterol levels. Conclusions: The prevalence of RVO in this Asian population was lower than Caucasians in the BMES, although the systemic associations of RVO were largely similar to BMES and other studies.

Intravitreal Bevacizumab in Inflammatory Ocular Neovascularization

PURPOSE To assess the role of bevacizumab in inflammatory ocular neovascularization. DESIGN Retrospective, multicenter, consecutive case series of inflammatory ocular neovascularization. METHODS Patients with inflammatory ocular neovascularization of varying causes for whom standard therapy failed were treated with intravitreal injection of bevacizumab. Main outcome measures included improvement of best-corrected visual acuity (BCVA) expressed in logarithm of minimum angle of resolution units, response of inflammatory ocular neovascularization by funduscopy and angiography, and decrease in central foveal thickness as measured by optical coherence tomography at the three-month follow-up. RESULTS At the three-month follow-up, 84 eyes of 79 patients had been treated with a mean of 1.3 injections (range, one to three). Thirty-four eyes showed juxtafoveal choroidal neovascularization (CNV), 34 eyes showed subfoveal CNV, eight eyes showed peripapillary CNV, and 11 eyes showed neovascularization of the disc (NVD) or neovascularization elsewhere (NVE). BCVA improved 2.4 lines from 0.68 (6/28 or 20/94) to 0.44 (6/17 or 20/55) (P < .001). BCVA improved by one to three lines in 34.5% of the eyes, by four to six lines in 16.7% of the eyes, and by more than six lines in 14.2% of the eyes. Function was unchanged in 23.8% of the eyes. BCVA worsened in 10.7% (zero to three lines in 7.1%, more than four lines in 3.6%). Central foveal thickness decreased from baseline 346 to 252 microm (P < .001). For CNV, 32 eyes (43.2%) had complete regression after the injection, 27 (36.5%) had partial regression, five (6.8%) had no response, and 10 eyes (13.5%) were not evaluated by the contributors. For NVD or NVE, seven eyes (63.6%) had complete regression of new vessels and four eyes (36.4%) had partial regression after the injection. CONCLUSIONS Intravitreal bevacizumab led to short-term significant visual improvement and regression of inflammatory ocular neovascularization in a wide variety of inflammatory ocular diseases.

Impact of Cataract Surgery on Quality of Life in Patients with Early Age-Related Macular Degeneration

Purpose. To investigate if cataract surgery improves overall and specific areas of quality of life (QoL) in patients with early age-related macular degeneration (AMD) using the impact of vision impairment (IVI) questionnaire. Methods. Patients with visually significant cataract and early AMD, who were being considered for cataract surgery in the study eye, were recruited. Eligible patients were randomized to either “early surgery” or “standard surgery” (standard cataract surgery waiting time of 6 months) groups. The IVI, sociodemographic, and clinical data were collected. Rasch analysis was used to estimate QoL person measures at baseline and follow-up. The data were analyzed using repeated measures ANOVA. Effect sizes were calculated using Cohens d coefficient. Results. Fifty six patients (mean age = 78.5 years and visual acuity = 6/15) had one eye randomly allocated to either the early surgery (n = 29) or standard surgery (n = 27) groups. At follow-up, significant interaction effects were found for the overall IVI score [F(1,54) = 17.7; p < 0.001], the emotional well-being [F(1,54) = 13.4; p = 0.001], mobility and independence [F(1,54) = 13.4; p = 0.001], and reading and accessing information subscales [F(1,54) = 13.1; p = 0.001]. The standard surgery group systematically recorded worse scores at 6 months on all QoL measures whereas the early surgery group recorded significant gains (p < 0.001; Cohens d = 0.66 to 0.91) on all of them. Visual acuity in the study eye significantly improved in the early surgery group only (Cohens d = 1.1; p < 0.05) and improvement in log MAR lines read was identified as the single independent predictor of enhanced QoL explaining between 26 and 34% of the variance in the IVI scores. Conclusions. Cataract surgery is justified in patients with early AMD. It brings significant improvements in visual acuity, aspects of daily living, and overall QoL.

Microbial keratitis associated with extended wear of silicone hydrogel contact lenses

Traditional hydrogel soft contact lenses (SCL) have limited oxygen permeability.1, 2 Recently introduced silicone hydrogel SCL have much higher oxygen transmissibility (Dk/t O2), allowing near normal oxygen supply to the cornea during extended lid closure, and are hoped by some to address most of the problems related to corneal hypoxia encountered with previous extended wear soft contact lenses.1, 3 They have therefore been approved for up to 30 days of continuous wear in both Europe and Australia. Four cases of microbial keratitis in patients who were using silicone hydrogel SCL (either CibaVision Focus Night and Day lenses (Lotrafilicon A, fluorosiloxane hydrogel) or Bausch & Lomb PureVision lenses (Balafilcon A, silicone hydrogel)) on an extended wear basis are presented. The minimum amount of continuous wear was 24 hours. All cases were treated either in private or at the corneal clinic of the Royal Victorian Eye and Ear Hospital from December 2000 to February 2001. All the patients underwent a complete ophthalmic examination by a corneal specialist. Microbiological specimens were taken from all patients via cornea scrapings and were submitted for Gram and Blankophor staining, and bacterial and fungal cultures via direct inoculation onto sheep blood agar, chocolate agar, and Sabouraud agar. Bacterial sensitivities of cultured organisms were also obtained. Where possible, the contact lenses themselves were also sent for microbial cultures. Each case is described in brief, and a summary presented in Table 1. View this table: Table 1 Summary of case details This 22 year old man presented with a 2 day history of left ocular injection, pain, photophobia, and blurred vision. He was wearing CibaVision Focus Night and Day SCL continuously for 10 days at a time, discarding the lenses after a month of use. He had swum in the sea while wearing the same lenses 2 weeks before, after which …

Genetic Dissection of Acute Anterior Uveitis Reveals Similarities and Differences in Associations observed with Ankylosing Spondylitis

To use high‐density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS).

Rituximab therapy for refractory scleritis: results of a phase I/II dose-ranging, randomized, clinical trial.

OBJECTIVE To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory noninfectious scleritis. DESIGN Prospective, dose-ranging, randomized, double-masked phase I/II clinical trial. PARTICIPANTS Twelve patients with noninfectious scleritis refractory to systemic corticosteroid and ≥1 other systemic immunosuppressive agent were enrolled from January 2007 to March 2010. INTERVENTION Subjects were randomly assigned to 500 (n = 5) or 1000 mg (n = 7) dosing arms of rituximab intravenous infusions (500 or 1000 mg), given at study days 1 and 15. Initial responders with breakthrough inflammation after study week 24 were offered treatment with an additional cycle of 2 open-label rituximab 1000 mg infusions. MAIN OUTCOME MEASURES Primary outcomes were reduction of inflammation, as measured with a validated scleritis disease grading scale (SGS) and reduction in corticosteroid dose by ≥50%. Patients were characterized as responders to study therapy if ≥1 of these endpoints showed improvement and neither showed evidence of worsening. Secondary outcomes were improvement in visual acuity, reduction in pain, and improvement in patient and physician-reported global health assessment. RESULTS Of 12 enrolled patients, 9 met the SGS endpoint at or before week 24, and 4 additionally were able to reduce corticosteroid dose by ≥50%. With regard to secondary outcome measures, 11 and 9 patients showed improvement in patient and physician global health scores, respectively, and 7 patients had reduction in pain. Of 9 initial responders, 7 experienced breakthrough inflammation after 24 weeks and were treated with a second cycle of rituximab infusions. Four patients had significant objective or subjective worsening within 8 weeks of receiving rituximab; this event was averted in subsequent patients by treatment with peri-infusional oral corticosteroid. No other significant adverse events were noted. No differences in efficacy, toxicity, or likelihood of retreatment were noted between the dosing arms. CONCLUSIONS Rituximab was effective treatment for 9 of 12 enrolled patients with refractory, noninfectious scleritis at 24 weeks, although 7 required reinfusion with rituximab to maintain inflammatory control. The treatment was well-tolerated, and peri-infusional inflammatory exacerbations were managed successfully with oral corticosteroids. Further long-term studies are warranted to determine the safety and efficacy of rituximab in treating noninfectious scleritis and other ocular inflammatory diseases.