Zainab Khan

Prophylactic nepafenac and ketorolac versus placebo in preventing postoperative macular edema after uneventful phacoemulsification

Purpose To evaluate the efficacy of prophylactic ketorolac 0.5% versus nepafenac 0.1% versus placebo on macular volume 1 month after uneventful phacoemulsification and evaluate the health‐related quality‐of‐life (HRQOL) of topical nonsteroidal antiinflammatory drugs (NSAIDs) in the context of cataract surgery. Setting Hotel Dieu Hospital, Kingston, Ontario, Canada. Design Prospective placebo‐controlled parallel‐assignment double‐masked randomized clinical trial. Methods In this study, patients 18 years or older scheduled for routine phacoemulsification were randomized to a placebo, ketorolac 0.5%, or nepafenac 0.1% and dosed 4 times a day starting 1 day before surgery and continuing for 4 weeks. Spectral‐domain macular cube ocular coherence tomography scans measuring central subfield thickness, macular cube volume, and average macular cube thickness were performed at baseline and 1 month postoperatively. The HRQOL metrics were determined with the Comparison of Ophthalmic Medications for Tolerability (COMTOL) questionnaire. Results Each study group comprised 54 patients. One month postoperatively, although a trend toward significance occurred for nepafenac and ketorolac, analysis of the means of differences showed no statistically significant differences between the 3 study groups (P=.2901). The COMTOL analysis found no difference in tolerability, compliance, side‐effect frequency and bother, and effects on HRQOL between ketorolac and nepafenac compared with the placebo. Conclusions One month after uneventful phacoemulsification, there was no difference in macular volume between the placebo, ketorolac, and nepafenac. Ketorolac and nepafenac were well tolerated with minimal side‐effect profiles. Thus, for patients without risk factors having routine surgery, prophylactic topical NSAIDs are not recommended. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

10-Year Framingham risk in patients with retinal vein occlusion: a systematic review and meta-analysis

OBJECTIVE Cardiovascular risk factors predispose individuals to retinal vein occlusions (RVOs). Yet, the future risk for development of cardiovascular disease in persons with RVOs is uncertain. We performed a literature review and meta-analysis of studies to determine the 10-year Framingham risk for individuals with RVO. METHODS A literature search was performed in MEDLINE and EMBASE. Studies were eligible if they included subjects with RVO and presented data on age, sex, smoking status, systolic blood pressure, total cholesterol, and high-density lipoprotein. The 10-year Framingham risk was calculated. Sensitivity analysis was performed and hypothesis testing was carried out using the upper tail z test with α = 0.05 to compare the estimated Framingham risk in RVO patients with the risk in the general Canadian population. Subgroup meta-analysis was carried out by Cochrane Collaboration Review Manager 4.5 software (Cochrane IMS, Copenhagen, Denmark). RESULTS A final list of 6 articles was included. The estimated 10-year Framingham risk score in subjects with RVO was 10.1% (95% CI 9.9-10.2). Sensitivity analysis found Framingham risk score to be greatest in male smokers. The Framingham risk in subjects with RVO was significantly greater than the general Canadian population. In a subgroup analysis, the 10-year risk was significantly greater in subjects with RVO compared with control subjects. CONCLUSIONS Patients with RVO have an increased 10-year risk for cardiovascular disease. This risk is greatest for male smokers (high risk). These patients may benefit from therapy aimed at controlling their risk factors. All individuals with an increased Framingham risk should be warned about vision loss as a potential complication of systemic atherosclerotic disease.

Efficacy of the Intravitreal Sustained-Release Dexamethasone Implant for Diabetic Macular Edema Refractory to Anti-Vascular Endothelial Growth Factor Therapy: Meta-Analysis and Clinical Implications

BACKGROUND AND OBJECTIVE To assess the effect on best-corrected visual acuity (BCVA) and efficacy of the intravitreal sustained-release 0.7 mg dexamethasone implant (Ozurdex; Allergan, Irvine, CA) in patients with recalcitrant diabetic macular edema (DME). PATIENTS AND METHODS Meta-analysis utilizing the MOOSE framework and a random effects model. Studies included adults undergoing treatment with Ozurdex for DME. The methodologic quality of each study was assessed using the MINORS and the Cochrane Collaboration Risk of Bias for randomized studies. RESULTS A total of 3,859 patients among 15 studies were included in the final analysis. The mean difference in BCVA was a gain of four lines or 20 Early Treatment of Diabetic Retinopathy Study letters with Ozurdex at a mean follow-up period of 6 months. CONCLUSIONS Treatment with Ozurdex is associated with significant mean improvement in visual acuity. Clinicians should have a multimodality approach to treating DME and be aware of this treatment option in those who have a suboptimal response to anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:160-166.].

Burden and Depression among Caregivers of Visually Impaired Patients in a Canadian Population.

Purpose/Background. This study reports the degree of burden and the proportion at risk for depression among individuals who provide care to visually impaired patients. Study Design. This is clinic-based, cross-sectional survey in a tertiary care hospital. Methods. Caregivers were considered unpaid family members for patients whose sole impairment was visual. Patients were stratified by vision in their better seeing eye into two groups: Group 1 had visual acuity between 6/18 and 6/60 and Group 2 were those who had 6/60 or worse. Burden was evaluated by the Burden Index of Caregivers and the prevalence of being at risk for depression was determined by the Center for Epidemiologic Studies Depression scale. Results. 236 caregivers of 236 patients were included. Total mean BIC scores were higher in Group 2. Female caregivers, caregivers providing greater hours of care, and caregivers of patients who have not completed vision rehabilitation programs are at higher risk for depression.

Depression and burden among the caregivers of visually impaired patients: a systematic review

Caregiving has evolved as an important issue not only for those receiving care, but for those providing it as well. While caregiving allows those with disabilities to better adapt, it has been shown to take a toll on the caregiver on various levels, such as invoking depression and burden. The purpose of this study was to perform a systematic review of the literature pertaining to depression and burden among caregivers of patients with visual impairment. A comprehensive literature search using multiple databases was conducted to include all articles on burden of care or depression among the caregivers of the visually impaired. Nine studies were included in this review. There was demonstrable association of depression and burden with the caregivers of the visually impaired. Communication theory, emotional contagion, and care burden were cited as factors associated with depression in these studies. A number of other elements were also identified to play a role in depression and burden, such as providing greater hours of supervision to the patient, multiple chronic conditions in the patient or caregiver, patient not completing vision rehabilitation, and female gender of the caregiver. By identifying those at risk for decreased quality of life outcomes, health care providers may be able to alter the management of the visually impaired, such as advocating the use of vision rehabilitation clinics in order to minimize the caregiver burden and depression.

Summary of Glaucoma Diagnostic Testing Accuracy: An Evidence-Based Meta-Analysis.

Background New glaucoma diagnostic technologies are penetrating clinical care and are changing rapidly. Having a systematic review of these technologies will help clinicians and decision makers and help identify gaps that need to be addressed. This systematic review studied five glaucoma technologies compared to the gold standard of white on white perimetry for glaucoma detection. Methods OVID® interface: MEDLINE® (In-Process & Other Non-Indexed Citations), EMBASE®, BIOSIS Previews®, CINAHL®, PubMed, and the Cochrane Library were searched. A gray literature search was also performed. A technical expert panel, information specialists, systematic review method experts and biostatisticians were used. A PRISMA flow diagram was created and a random effect meta-analysis was performed. Results A total of 2,474 articles were screened. The greatest accuracy was found with frequency doubling technology (FDT) (diagnostic odds ratio (DOR): 57.7) followed by blue on yellow perimetry (DOR: 46.7), optical coherence tomography (OCT) (DOR: 41.8), GDx (DOR: 32.4) and Heidelberg retina tomography (HRT) (DOR: 17.8). Of greatest concern is that tests for heterogeneity were all above 50%, indicating that cutoffs used in these newer technologies were all very varied and not uniform across studies. Conclusions Glaucoma content experts need to establish uniform cutoffs for these newer technologies, so that studies that compare these technologies can be interpreted more uniformly. Nevertheless, synthesized data at this time demonstrate that amongst the newest technologies, OCT has the highest glaucoma diagnostic accuracy followed by GDx and then HRT.

Low power and type II errors in recent ophthalmology research

OBJECTIVE To investigate the power of unpaired t tests in prospective, randomized controlled trials when these tests failed to detect a statistically significant difference and to determine the frequency of type II errors. DESIGN Systematic review and meta-analysis. METHODS We examined all prospective, randomized controlled trials published between 2010 and 2012 in 4 major ophthalmology journals (Archives of Ophthalmology, British Journal of Ophthalmology, Ophthalmology, and American Journal of Ophthalmology). Studies that used unpaired t tests were included. Power was calculated using the number of subjects in each group, standard deviations, and α = 0.05. The difference between control and experimental means was set to be (1) 20% and (2) 50% of the absolute value of the controls initial conditions. Power and Precision version 4.0 software was used to carry out calculations. Finally, the proportion of articles with type II errors was calculated. β = 0.3 was set as the largest acceptable value for the probability of type II errors. RESULTS In total, 280 articles were screened. Final analysis included 50 prospective, randomized controlled trials using unpaired t tests. The median power of tests to detect a 50% difference between means was 0.9 and was the same for all 4 journals regardless of the statistical significance of the test. The median power of tests to detect a 20% difference between means ranged from 0.26 to 0.9 for the 4 journals. The median power of these tests to detect a 50% and 20% difference between means was 0.9 and 0.5 for tests that did not achieve statistical significance. A total of 14% and 57% of articles with negative unpaired t tests contained results with β > 0.3 when power was calculated for differences between means of 50% and 20%, respectively. CONCLUSIONS A large portion of studies demonstrate high probabilities of type II errors when detecting small differences between means. The power to detect small difference between means varies across journals. It is, therefore, worthwhile for authors to mention the minimum clinically important difference for individual studies. Journals can consider publishing statistical guidelines for authors to use. Day-to-day clinical decisions rely heavily on the evidence base formed by the plethora of studies available to clinicians. Prospective, randomized controlled clinical trials are highly regarded as a robust study and are used to make important clinical decisions that directly affect patient care. The quality of study designs and statistical methods in major clinical journals is improving overtime,1 and researchers and journals are being more attentive to statistical methodologies incorporated by studies. The results of well-designed ophthalmic studies with robust methodologies, therefore, have the ability to modify the ways in which diseases are managed.

Letter to the Editor: Efficacy of the Intravitreal Sustained-Release Dexamethasone Implant for DME Refractory to Anti-VEGF Therapy: Meta-Analysis and Clinical Implications

Dear Editor, We have significant concerns regarding the methodology used in the Khan et al.1 meta-analysis and the subsequent size of treatment effect reported. In particular, the result stating that “patients treated with dexamethasone implants for diabetic macular edema (DME) refractory to anti-VEGF [vascular endothelial growth factor] therapy gained a mean of four lines (20 logMAR letters)” appears inaccurate, as none of the included studies reported a treatment effect of the same magnitude. There are several methodological weaknesses highlighted below.