Samir N. Patel

CENTRAL SEROUS CHORIORETINOPATHY TREATED WITH MINERALOCORTICOID ANTAGONISTS: A ONE-YEAR PILOT STUDY.

Purpose: To assess the treatment response to mineralocorticoid antagonists in a pilot study of patients diagnosed with central serous chorioretinopathy using multimodal imaging. Methods: This retrospective observational case series included 23 eyes of 14 patients with central serous chorioretinopathy treated by a single physician (L.A.Y.) with either spironolactone, eplerenone, or both consecutively over a 12-month period. Choroidal thickness, central macular thickness, and best-corrected visual acuity were measured and compared with baseline values. Twelve eyes of 11 patients demonstrated subretinal fluid before or during the initiated treatment course. Subretinal fluid was measured and compared with baseline values in this subgroup. Results: In all eyes (n = 23), best-corrected visual acuity improved at 12 months of treatment; however, central macular thickness and choroidal thickness showed no improvement. In the subgroup with subretinal fluid (n = 12), subretinal fluid was significantly decreased at 6 months and 12 months of treatment; however, central macular thickness, choroidal thickness, and best-corrected visual acuity showed no significant change. Conclusion: Mineralocorticoid antagonists may improve best-corrected visual acuity and decrease subretinal fluid in patients with central serous chorioretinopathy, but do not affect the choroidal or macular thickness. This pilot study demonstrates that mineralocorticoid receptor antagonists may be effective in treating central serous chorioretinopathy but warrants consideration for future research within a randomized clinical trial.

Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration

With the advent of anti-vascular endothelial growth factor (VEGF) therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD), a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA) alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT) and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER) with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes) were followed over an average of 3.5 years (range 1–6.6) with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6) (± standard deviation) intravitreal anti-VEGF injections/year (range 4–13). The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.

Baseline Predictors for Good Versus Poor Visual Outcomes in the Treatment of Neovascular Age-Related Macular Degeneration With Intravitreal Anti-VEGF Therapy.

PURPOSE To examine the baseline factors associated with good (20/60 or better) versus poor (20/200 or worse) visual outcomes in eyes with treatment-naïve neovascular age-related macular degeneration (AMD) receiving intravitreal antivascular endothelial growth factor (VEGF) on a treat-and-extend regimen (TER). METHODS An observational, retrospective series of patients managed with a TER, identified as having either good or poor visual outcomes, was examined. A multivariate regression analysis of baseline characteristics identified factors associated with good and poor vision at 2, 3, and 4 years. Neovascular subtypes were identified using fluorescein angiography (FA) alone and the anatomic classification system with FA and optical coherence tomography (OCT). RESULTS One hundred thirty-eight patients (154 eyes) fit the inclusion criteria at 2 years, 106 patients (113 eyes) at 3 years, and 72 patients (74 eyes) at 4 years. In the multivariate analysis, type 1 lesions, according to anatomic classification, had better vision at 24 months (95% CI: [3.1, 82.7], P = 0.01), 36 months (95% CI: [1.97, 24.17], P = 0.003), and 48 months (95% CI: [2.01, 65.47], P = 0.006). Clopidogrel use was associated with poor vision at 24 months (95% CI: [0.03, 0.68], P = 0.013). Vision at 3 months was the best predictor of vision at year 4 (β = -4.277, P = 0.002). CONCLUSIONS Eyes with neovascular AMD managed with a TER of anti-VEGF therapy having type 1 neovascularization at baseline were more likely to maintain good vision over 4 years, whereas clopidogrel use predicted poor vision at 2 years. Vision at 3 months was the best predictor for favorable long-term vision.

Expert Diagnosis of Plus Disease in Retinopathy of Prematurity From Computer-Based Image Analysis

IMPORTANCE Published definitions of plus disease in retinopathy of prematurity (ROP) reference arterial tortuosity and venous dilation within the posterior pole based on a standard published photograph. One possible explanation for limited interexpert reliability for a diagnosis of plus disease is that experts deviate from the published definitions. OBJECTIVE To identify vascular features used by experts for diagnosis of plus disease through quantitative image analysis. DESIGN, SETTING, AND PARTICIPANTS A computer-based image analysis system (Imaging and Informatics in ROP [i-ROP]) was developed using a set of 77 digital fundus images, and the system was designed to classify images compared with a reference standard diagnosis (RSD). System performance was analyzed as a function of the field of view (circular crops with a radius of 1-6 disc diameters) and vessel subtype (arteries only, veins only, or all vessels). Routine ROP screening was conducted from June 29, 2011, to October 14, 2014, in neonatal intensive care units at 8 academic institutions, with a subset of 73 images independently classified by 11 ROP experts for validation. The RSD was compared with the majority diagnosis of experts. MAIN OUTCOMES AND MEASURES The primary outcome measure was the percentage of accuracy of the i-ROP system classification of plus disease, with the RSD as a function of the field of view and vessel type. Secondary outcome measures included the accuracy of the 11 experts compared with the RSD. RESULTS Accuracy of plus disease diagnosis by the i-ROP computer-based system was highest (95%; 95% CI, 94%-95%) when it incorporated vascular tortuosity from both arteries and veins and with the widest field of view (6-disc diameter radius). Accuracy was 90% or less when using only arterial tortuosity and 85% or less using a 2- to 3-disc diameter view similar to the standard published photograph. Diagnostic accuracy of the i-ROP system (95%) was comparable to that of 11 expert physicians (mean 87%, range 79%-99%). CONCLUSIONS AND RELEVANCE Experts in ROP appear to consider findings from beyond the posterior retina when diagnosing plus disease and consider tortuosity of both arteries and veins, in contrast with published definitions. It is feasible for a computer-based image analysis system to perform comparably with ROP experts, using manually segmented images.

Predictors of Sustained Intraocular Pressure Elevation in Eyes Receiving Intravitreal Anti–Vascular Endothelial Growth Factor Therapy

PURPOSE To determine the intravitreal anti-vascular endothelial growth factor (VEGF) injection techniques and preferences within the retinal community and to identify potential factors associated with the development of sustained intraocular pressure (IOP) elevation in patients treated with intravitreal anti-VEGF therapy for neovascular age-related macular degeneration (AMD). DESIGN Cross-sectional physician survey. METHODS Five hundred and thirty retina specialists spanning both private and academic practices were surveyed regarding current anti-VEGF intravitreal injection protocols, including the anti-VEGF drug of choice, needle gauge, injection volume, injection technique, and self-reported prevalence of sustained IOP elevation. Multivariate logistic regressions were performed to assess the potential influence of these factors on long-term IOP. RESULTS Two hundred ninety-two specialists (55%) reported believing that intravitreal anti-VEGF therapy may cause sustained IOP elevation. Of these responses, the most common reported prevalence was 1%-2% (48%), followed by 3%-5% (34%). There was no relationship between the frequency of sustained IOP elevation and anti-VEGF drug of choice. Physicians who injected greater than 0.05 cc in less than 1 second were 5.56 times more likely to observe a high frequency of sustained IOP elevation (P=.006, 95% CI 1.64-18.89). CONCLUSIONS Based on physician survey data, serial anti-VEGF injections using higher injection volumes with a rapid injection technique may potentially lead to sustained IOP elevation. The underlying mechanism for this complication may be injury to the trabecular meshwork resulting from rapid elevations in IOP. Further investigation of the relationship between injection techniques and sustained IOP elevation in the form of retrospective or prospective clinical studies is warranted.

Influence of Fluorescein Angiography on the Diagnosis and Management of Retinopathy of Prematurity

PURPOSE To examine the influence of fluorescein angiography (FA) on the diagnosis and management of retinopathy of prematurity (ROP). DESIGN Prospective cohort study. PARTICIPANTS Nine recognized ROP experts (3 pediatric ophthalmologists and 6 retina specialists) interpreted 32 sets (16 color fundus photographs and 16 color fundus photographs paired with the corresponding FA images) of wide-angle retinal images from infants with ROP. METHODS All experts independently reviewed the 32 image sets on a secure website and provided a diagnosis and management plan for the case presented, first based on color fundus photographs alone, and then based on color fundus photographs and corresponding FA images. MAIN OUTCOME MEASURES Sensitivity and specificity of the ROP diagnosis (zone, stage, plus disease, and category, i.e., no ROP, mild ROP, type 2 ROP, and ROP requiring treatment) were calculated using a consensus reference standard diagnosis, determined from the diagnosis of the color fundus photographs by 3 experienced readers in combination with the clinical diagnosis based on ophthalmoscopic examination. The κ statistic was used to analyze the average intergrader agreement among experts for the diagnosis of zone, stage, plus disease, and category. RESULTS Addition of FA to color fundus photography resulted in a significant improvement in sensitivity for diagnosis of stage 3 or worse disease (39.8% vs. 74.1%; P = 0.008), type 2 or worse ROP (69.4% vs. 86.8%; P = 0.013), and pre-plus or worse disease (50.5 vs. 62.6%; P = 0.031). There was a nonsignificant trend toward improved sensitivity for diagnosis of ROP requiring treatment (22.2% vs. 40.3%; P = 0.063). Using the κ statistic, addition of FA to color fundus photography significantly improved intergrader agreement for diagnosis of ROP requiring treatment. Addition of FA to color fundus photography did not affect intergrader agreement significantly for the diagnosis of stage, zone, or plus disease. CONCLUSIONS Compared with color fundus photography alone, FA may improve the sensitivity of diagnosis of ROP by experts, particularly for stage 3 disease. In addition, intergrader agreement for diagnosis of ROP requiring treatment may improve with FA interpretation.

Color Fundus Photography Versus Fluorescein Angiography in Identification of the Macular Center and Zone in Retinopathy of Prematurity

PURPOSE To examine the usefulness of fluorescein angiography (FA) in identifying the macular center and diagnosis of zone in patients with retinopathy of prematurity (ROP). DESIGN Validity and reliability analysis of diagnostic tools. METHODS Thirty-two sets (16 color fundus photographs and 16 color fundus photographs paired with the corresponding FA images) of wide-angle retinal images obtained from 16 eyes of 8 infants with ROP were compiled on a secure web site. Nine ROP experts (3 pediatric ophthalmologists and 6 vitreoretinal surgeons) participated in the study. For each image set, experts identified the macular center and provided a diagnosis of zone. MAIN OUTCOME MEASURES (1) Sensitivity and specificity of zone diagnosis and (2) computer-facilitated diagnosis of zone, based on precise measurement of the macular center, optic disc center, and peripheral ROP. RESULTS Computer-facilitated diagnosis of zone agreed with the experts diagnosis of zone in 28 (62%) of 45 cases using color fundus photographs and in 31 (69%) of 45 cases using FA images. Mean (95% confidence interval) sensitivity for detection of zone I by experts compared with a consensus reference standard diagnosis when interpreting the color fundus images alone versus interpreting the color fundus photographs and FA images was 47% (range, 35.3% to 59.3%) and 61.1% (range, 48.9% to 72.4%), respectively (t(9) ≥ (2.063); P = .073). CONCLUSIONS There is a marginally significant difference in zone diagnosis when using color fundus photographs compared with using color fundus photographs and the corresponding FA images. There is inconsistency between traditional zone diagnosis (based on ophthalmoscopic examination and image review) compared with a computer-facilitated diagnosis of zone.

The Effect of Smoking on 30-Day Complications Following Radical Prostatectomy

Micro‐Abstract To assess if smoking is associated with postoperative complications following radical prostatectomy, the National Surgical Quality Improvement Program database was analyzed. Of the 22,802 patients identified, current smokers had higher rates of pneumonia and unplanned intubation. Current smoking status as independent predictor of unplanned intubation was verified in multivariable analysis. Smoking status influences the risk of postoperative complications following prostatectomy. Objective: The purpose of this study was to determine if smoking status is associated with 30‐day postoperative complications following radical prostatectomy. Methods: From the American College of Surgeons National Surgical Quality Improvement Programs (NSQIP) 2005‐2013 database, we identified patients who underwent prostatectomy for treatment of prostate cancer. The cohort was stratified into current smokers, former smokers, and never smokers. Bivariable and multivariable analysis was utilized to assess the association between smoking status and risk of complications. Results: We identified 22,802 patients who underwent malignancy‐related prostatectomy and met inclusion criteria. Based on reported smoking history, 2799 (12.3%) were current smokers, 1879 (8.2%) were former smokers, and 18,124 (79.5%) were never smokers. Current smokers had a higher rate of total complications (5.7%) in comparison with former (4.8%) and never smokers (4.6%; P = .050). Postoperative pneumonia was more frequent in current smokers (0.4%) compared with former smokers (0.2%) and never smokers (0.2%; P = .039). Unplanned intubation occurred more frequently in current smokers (0.4%) when compared with former smokers (0.3%) and never smokers (0.1%; P = .002). Multivariable analysis found that current smoking status was an independent predictor of an increased risk of unplanned intubation (odds ratio, 5.87; 95% confidence interval, 2.18‐15.8; P < .001). Conclusion: Smoking status influences the risk of postoperative complications following prostatectomy. Specifically, current smoking status is an independent predictor of unplanned intubation within 30 days of the procedure.

Retinal vascular nonperfusion in siblings with Dandy-Walker variant

We report the case of a 2-month-old girl with Dandy-Walker variant who presented with strabismus, pathologic myopia measuring -16.00 D in each eye, diffuse chorioretinal atrophy and pigment mottling in the macula of both eyes, and areas of retinal capillary nonperfusion in both eyes. The patients brother also has Dandy-Walker variant and was found to have bilateral severe myopia, myopic fundi, tilted optic disks with peripapillary atrophy, extensive areas of white without pressure, areas of lattice degeneration, and several chronic-appearing atrophic retinal holes surrounded by pigmentation. We hypothesize that children with Dandy-Walker variant may present with refractive errors such as pathologic myopia and with diverse retinal findings, including retinal ischemia. A lower threshold for ophthalmologic examination may be considered in this population.

Inconsistencies in the diagnosis of aggressive posterior retinopathy of prematurity

Purpose: To determine the accuracy and reliability of diagnosing aggressive posterior retinopathy of prematurity (AP-ROP). Methods: A total of 1220 eye examinations from 230 infants were prospectively obtained at 8 major ROP centers. An ophthalmologist at each center provided a clinical diagnosis using indirect ophthalmoscopy. Wide-angle retinal images were then obtained, which were independently read by 2 ROP experts using a web-based system for an image-based diagnosis. Sensitivity and specificity of image-based AP-ROP diagnosis by the ROP experts were calculated using the clinical diagnosis as the reference standard. Agreement of AP-ROP diagnosis through image-based diagnosis and clinical diagnosis was calculated using the unweighted κ statistic. Results: One hundred four (9%) of the 1220 examinations had a clinical diagnosis of AP-ROP. Sensitivity and specificity for the presence of AP-ROP were 35% and 96% for expert 1 and 17% and 99% for expert 2. Using the κ statistic, expert image-based versus clinical diagnostic agreement for the diagnosis of AP-ROP was 0.34 (fair) for expert 1 and 0.24 (fair) for expert 2. Agreement for the diagnosis of AP-ROP between the image-based diagnoses of expert 1 and expert 2 was 0.49 (moderate). Conclusion: There are inconsistencies between the clinical diagnosis of AP-ROP (as determined by indirect ophthalmoscopy) and the image-based diagnosis of AP-ROP. This may have important implications for ROP management and the current international ROP classification system.