Impact of anti-VEGF treatment on development of proliferative diabetic retinopathy in routine clinical practice.

BACKGROUND: This study evaluated impact of anti-vascular endothelial growth factor (VEGF) treatment on proliferative diabetic retinopathy (PDR) development among patients with non-proliferative diabetic retinopathy (NPDR) in US real-world clinical practice. METHODS: This was a retrospective analysis of electronic medical records (Vestrum Health; January 2013 to June 2019) of eyes with baseline NPDR, without DME, and naïve to anti-VEGF treatment at index DR diagnosis. Eyes that received anti-VEGF and/or laser treatment over the course of study before development of PDR constituted the treated cohort while the remaining including those treated with laser constituted the anti-VEGF naïve cohort. Survival analysis via Kaplan-Meier method evaluated time to DME and PDR development by baseline NPDR severity, with anti-VEGF treatment as censoring variable. Baseline factors affecting PDR development were analyzed using Cox multivariable regression, censoring for anti-VEGF treatment. RESULTS: Among anti-VEGF-naive eyes, cumulative incidence of DME in eyes with mild (n = 70,050), moderate (n = 39,116), and severe NPDR (n = 10,692) at baseline was 27.1%, 51.2%, and 60.6%. Multivariable regression analysis identified baseline NPDR severity as the most significant predictor of PDR development over 48 months (hazard ratio [HR] [95% confidence interval {CI}] of 2.69 (2.65-2.72) for moderate vs mild NPDR and 6.51 (6.47-6.55) for severe vs mild NPDR). Cumulative incidence (95% CI) of PDR was 7.9% (7.4%-8.3%), 20.9%, (20.0%-21.7%) and 46.8% (44.4%-49.2%) over 48 months in eyes with mild, moderate, and severe NPDR at baseline, respectively. Among treated eyes with baseline severe NPDR, cumulative incidence of PDR at 48 months was 50.1% in eyes treated with laser (n = 546; HR [95% CI] vs no treatment: 0.8 [0.7-1.0]), 27.4% in eyes treated with anti-VEGF (n = 923; HR [95% CI]: 0.4 [0.4-0.5]), and 25.6% in eyes treated with anti-VEGF plus laser (n = 293; HR [95% CI]: 0.5 [0.4-0.7]) compared with 49.9% in eyes with no treatment (n = 8930). CONCLUSIONS: DME and PDR development rates increased with increasing baseline NPDR severity. Approximately half of anti-VEGF‒naive eyes with severe NPDR progressed to PDR within 4 years in US clinical practice. The progression rate from severe NPDR to PDR was approximately halved with anti-VEGF versus no treatment.

Factors associated with diabetic macular edema in patients with proliferative diabetic retinopathy.

PURPOSE: To identify factors associated with diabetic macular edema (DME) and to characterize the types of DME present in eyes with proliferative diabetic retinopathy (PDR). METHODS: Observational, retrospective case series of PDR patients reviewed for demographic information, general medical history, ophthalmologic history, optical coherence tomography (OCT), and fluorescein angiogram image characteristics. DME and vitreomacular interface (VMI) status were determined using OCT images. DME was defined as center-involving DME (CI-DME) and noncenter-involving DME (NCI-DME). VMI was defined as vitreomacular adhesion (VMA), vitreomacular traction (VMT), or macular posterior vitreous detachment (PVD). RESULTS: A total of 293 eyes of 210 screened patients with PDR were included. Of the eyes, 194/293 (66.2%) had DME, and 99/293 (33.8%) had no DME; in univariable analysis, there were no significant differences in VMI status (p = 0.4) or epiretinal membrane (ERM, p = 0.1) between them. Of 194 eyes with DME, 90/194 (46.4%) had CI-DME, and 104/194 (53.6%) had NCI-DME. In univariable analysis, CI-DME eyes were significantly more likely than NCI-DME eyes to have a PVD (p = 0.029) and ERM (p < 0.001). In multivariable analysis, the presence of younger age (p = 0.028) and presence of ERM (p = 0.001) were significantly more likely to be observed in eyes with CI-DME. CONCLUSION: In this exploratory study focused on diabetic patients with PDR, we determined that VMI status did not have a significant association with DME in general, but VMI status, younger age, and presence of ERM may be associated with CI-DME.

LONG-TERM VISUAL OUTCOMES AND CLINICAL FEATURES AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION-RELATED ENDOPHTHALMITIS.

PURPOSE: To determine long-term visual outcomes in patients who developed endophthalmitis after intravitreal anti-vascular endothelial growth factor injections and to correlate visual outcomes with clinical features. METHODS: This is a retrospective, multicenter, consecutive case series of patients diagnosed with anti-vascular endothelial growth factor injection-related endophthalmitis who were treated at Mid Atlantic Retina, the Retina Service of Wills Eye Hospital, Philadelphia, PA, and the University of Southern California Roski Eye Institute, Los Angeles, CA. Patients were included if they had at least 1 year of follow-up. Primary outcome was to evaluate long-term visual outcomes up to 5 years of follow-up. The secondary outcome was to determine clinical features (e.g., culture results) that may predict long-term visual acuity outcomes. RESULTS: A total of 56 cases of endophthalmitis from 168,247 anti-vascular endothelial growth factor injections were identified (0.033%, 1/3,004 injections), from which 51 eyes met inclusion criteria. Mean follow-up period was 3.3 years (median 4 years; range 1-5 years). A total of 24 patients (47%) reached a maximum final follow-up of 5 years. Mean Snellen visual acuity at the causative injection visit was 20/102 and decreased to counting fingers at diagnosis (P < 0.001). At 6-month follow-up, mean visual acuity improved to 20/644 (P < 0.001) and remained stable up to 5 years (20/480, P = 0.003) follow-up compared with diagnosis. At the final follow-up, 20 eyes had visual acuity that returned to within one line of baseline visual acuity (visual recovery group), whereas 31 patients' visual acuity was at least one line worse than initial visual acuity (visual deterioration group). The cultures for the visual recovery group were more likely to grow coagulase-negative Staphylococcus, whereas the visual deterioration group primarily grew Streptococcus species, Staphylococcus aureus, and Enterococcus faecalis (P = 0.002, comparing organisms isolated in the visual recovery and deterioration group). CONCLUSION: Visual outcomes after anti-vascular endothelial growth factor injection-related endophthalmitis seem to reach peak improvement by 6 months and remain stable up to a median of 4-year follow-up. Patients who develop culture-negative endophthalmitis or endophthalmitis secondary to coagulase-negative Staphylococcus are more likely to regain baseline visual acuity compared with cases secondary to Streptococcus species.

A novel classification of high myopia into anterior and posterior pathologic subtypes.

PURPOSE: High myopia and pathologic myopia are common causes of visual morbidity. Myopic pathology can affect all regions of the retina, though there is currently no classification system to distinguish anterior (peripheral) and posterior (macular) pathology. We hypothesize that these classifications are characterized by distinct demographic and refractive features, highlighting the disparity in types of pathologic myopia. METHODS: Institutional retrospective cohort study. The Stanford University Medical Center Clinical Data Warehouse was used to identify patients with high myopia by ICD-9 and ICD-10 codes. Predetermined ICD diagnoses were then used to classify patients with high myopia into isolated high myopia (IHM), anterior pathologic myopia (APM), posterior pathologic myopia (PPM), and combined pathologic myopia (CPM). A cohort of this population was then manually reviewed to gather refractive data and confirm accuracy of ICD coding. RESULTS: Patients (3274) were identified with high myopia. Overall, 22.1% individuals met criteria for APM, 10.7% for PPM, 17.0% for CPM, and 50.2% for IHM. We identified a significantly higher frequency of females with PPM compared to APM (62.3 vs. 48.3%; OR, 1.73; 95% CI, 1.34 to 2.25), Asian patients with PPM as compared to APM (42.9 vs. 33.3%; OR, 1.50; 95% CI, 1.16 to 1.95), and younger patients with APM compared to PPM (median 45.3 vs. 63.4 years). The refractive error was significantly more myopic in the CPM (median - 9.8D; interquartile range, IQR 6.7) and PPM (median - 10.5D; IQR 9.8) subgroups as compared to the APM (median - 8.1D; IQR 3.5), and IHM (median - 8.2D; IQR 4.1) subgroups (p = 0.003). CONCLUSIONS: High myopia may be divided into four distinct subgroups based on presence and location of pathology, which is associated with differences in age, gender, race, and refractive error.

Rates of Reoperation and Retinal Detachment after Macular Hole Surgery.

PURPOSE: To evaluate rates of reoperation and retinal detachment (RD) after macular hole surgery. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Patients in the insurance claim-based MarketScan databases from 2007 through 2013 with a record of macular hole surgery. METHODS: Patients with macular hole surgery were identified. Cases of definite (the same eye was coded both times) and presumed (the eye laterality was not coded) macular hole reoperations within 2, 3, and 12 months were queried. In addition, cases of postoperative RD within 2, 3, and 12 months were captured. MAIN OUTCOME MEASURES: Rates of macular hole reoperation and postoperative RD, including subgroup analysis based on presence or absence of internal limiting membrane (ILM) peeling. RESULTS: Records of 23465 macular hole surgeries among 20 764 patients were analyzed. Among presumed reoperations, the rates of reoperation were 4.3% (4.1% after ILM peeling and 5.0% after no ILM peeling; P = 0.01) within 2 months of surgery, 5.5% (5.3% after ILM peeling and 6.2% after no ILM peeling; P = 0.03) within 3 months of surgery, and 9.5% (9.0% after ILM peeling and 11.0% after no ILM peeling; P = 0.01) within 12 months of surgery. The rates for definite reoperations were 1.3% (1.2% after ILM peeling and 1.8% after no ILM peeling; P = 0.04) at 2 months, 1.7% (1.6% after ILM peeling and 2.5% after no ILM peeling; P = 0.004) at 3 months, and 4.1% (3.3% after ILM peeling and 7.5% after no ILM peeling; P < 0.001) at 12 months. The cumulative rate of postoperative RD was 1.81±0.09% to 2.18±0.5% after 2 months, 2.27±0.10% to 3.18±0.67% after 3 months, and 3.92±0.16% to 5.70±1.1% after 12 months. Internal limiting membrane peeling was associated negatively with postoperative RD at 2 months (2.3% vs. 1.7%; P = 0.007), 3 months (2.8% vs. 2.1%; P = 0.004), and 12 months (4.7% vs. 3.3%; P < 0.001). CONCLUSIONS: In this sample, reoperations for macular hole were performed at low rates. Internal limiting membrane peeling was associated with lower rates of reoperation and RD.

Postoperative Hemorrhagic Occlusive Retinal Vasculitis: Expanding the Clinical Spectrum and Possible Association with Vancomycin.

PURPOSE: To describe a syndrome of hemorrhagic occlusive retinal vasculitis (HORV) that developed after seemingly uncomplicated cataract surgery. DESIGN: Retrospective case series. SUBJECTS: Eleven eyes of 6 patients from 6 different institutions. METHODS: Cases were identified after discussion among retina specialists. The findings on presentation, clinical course, and outcome of a series of 7 eyes of 4 patients were compared with a previous report of 4 eyes of 2 patients, and data from both series were combined for a comprehensive analysis. MAIN OUTCOME MEASURES: Historical data, examination findings, imaging results, systemic evaluation findings, treatment regimens, and visual outcomes. RESULTS: Eleven eyes of 6 patients underwent otherwise uncomplicated cataract surgery, receiving viscoelastic and prophylactic intracameral vancomycin during the procedure. Despite good initial vision on postoperative day 1, between 1 to 14 days after surgery, all eyes demonstrated painless vision loss resulting from HORV. Extensive ocular and systemic evaluations were unrevealing in all patients. All patients were treated with aggressive systemic and topical corticosteroids. Additional treatments included systemic antiviral medication in 4 patients, intravitreal antibiotics in 4 eyes, and pars plana vitrectomy in 4 eyes. Skin testing for vancomycin sensitivity showed negative results in 3 patients and was not performed in the others. Neovascular glaucoma developed in 7 eyes, and all eyes received intravitreal anti-vascular endothelial growth factor (VEGF) injection, panretinal photocoagulation, or both for retinal ischemia. Final visual acuity was less than 20/100 in 8 of 11 eyes. CONCLUSIONS: Postoperative HORV is an exceedingly rare and potentially devastating condition that can occur after otherwise uncomplicated cataract surgery. Although the precise cause remains unknown, this disease may represent a delayed immune reaction similar to vancomycin-induced leukocytoclastic vasculitis. Despite treatment with high-dose corticosteroids, antiviral medication, and early vitrectomy in many patients, visual outcomes typically were poor in this series. Early intervention with intravitreal anti-VEGF medication and panretinal photocoagulation may help to prevent additional vision loss resulting from neovascular glaucoma.

Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study.

PURPOSE: To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). DESIGN: Prospective, double-masked, randomized clinical trial. PARTICIPANTS: Patients with GA measuring from 1.25 to 18 mm(2) based on spectral-domain optical coherence tomography imaging. METHODS: Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and low-luminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores. MAIN OUTCOME MEASURES: Change in area of GA at 26 weeks. RESULTS: Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55 ± 0.94 and 2.02 ± 0.74 mm in the eculizumab and placebo groups, respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19 ± 0.12 and 0.18 ± 0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37 ± 0.22 mm in the eculizumab-treated eyes and by a mean of 0.37 ± 0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified. CONCLUSIONS: Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months.

Academic productivity and its relationship to physician salaries in the University of California Healthcare System.

OBJECTIVES: To evaluate whether physicians with higher academic productivity, as measured by the number of publications in Scopus and the Scopus Hirsch index (h-index), earn higher salaries. METHODS: This was a cross-sectional study. Participants were ophthalmologists, otolaryngologists, neurosurgeons, and neurologists classified as "top earners" (>$100,000 annually) within the University of California (UC) healthcare system in 2008. Bibliometric searches on Scopus were conducted to retrieve the total number of publications and Hirsch indices (h-index), a measure of academic productivity. The association between the number of publications and h-index on physicians' total compensation was determined with multivariate regression models after controlling for the four specialties (ophthalmology, otolaryngology, neurosurgery, and neurology), the five institutions (UC San Francisco, UC Los Angeles, UC San Diego, UC Irvine, and UC Davis), and academic rank (assistant professor, associate professor, and professor). RESULTS: The UC healthcare system departments reported 433 faculty physicians among the four specialties, with 71.6% (n = 310) earning more than $100,000 in 2008 and classifying as top earners. After controlling for the specialty, institution, and ranking, there was a significant association between the number of publications on salary (P < 0.000001). Scopus number of publications and h-index were correlated (P < 0.001). Scopus h-index was of borderline significance in predicting physician salary (P = 0.12). Physicians with higher Scopus publications had higher total salaries across all four specialties. Every 10 publications were associated with a 2.40% increase in total salary after controlling for specialty, institution, rank, and chair. CONCLUSIONS: Ophthalmologists, otolaryngologists, neurosurgeons, and neurologists in the UC healthcare system who are more academically productive receive greater remuneration.

Simulation of long-term impact of intravitreal anti-VEGF therapy on patients with severe non-proliferative diabetic retinopathy.

OBJECTIVE: A simulation model was constructed to assess long-term outcomes of proactively treating severe non-proliferative diabetic retinopathy (NPDR) with anti-vascular endothelial growth factor (anti-VEGF) therapy versus delaying treatment until PDR develops. METHODS AND ANALYSIS: Simulated patients were generated using a retrospective real-world cohort of treatment-naive patients identified in an electronic medical records database (IBM Explorys) between 2011 and 2017. Impact of anti-VEGF treatment was derived from clinical trial data for intravitreal aflibercept (PANORAMA) and ranibizumab (RISE/RIDE), averaged by weighted US market share. Real-world risk of PDR progression was modelled using Cox multivariable regression. The Monte Carlo simulation model examined rates of progression to PDR and sustained blindness (visual acuity <20/200) for 2 million patients scaled to US NPDR disease prevalence. Simulated progression rates from severe NPDR to PDR over 5 years and blindness rates over 10 years were compared for delayed versus early-treatment patients. RESULTS: Real-world data from 77 454 patients with mild-to-severe NPDR simulated 2 million NPDR patients, of which 86 680 had severe NPDR. Early treatment of severe NPDR with anti-VEGF therapy led to a 51.7% relative risk reduction in PDR events over 5 years (15 704 early vs 32 488 delayed), with a 19.4% absolute risk reduction (18.1% vs 37.5%). Sustained blindness rates at 10 years were 4.4% for delayed and 1.9% for early treatment of severe NPDR. CONCLUSION: The model suggests treating severe NPDR early with anti-VEGF therapy, rather than delaying treatment until PDR develops, could significantly reduce PDR incidence over 5 years and sustained blindness over 10 years.

Capillary density and caliber as assessed by optical coherence tomography angiography may be significant predictors of diabetic retinopathy severity.

PURPOSE: To validate retinal capillary density and caliber associations with diabetic retinopathy (DR) severity in different clinical settings. METHODS: This cross-sectional study assessed retinal capillary density and caliber in the superficial retinal layer of 3-mm OCTA scans centered on the fovea. Images were collected from non-diabetic controls and subjects with mild or referable DR (defined DR worse than mild DR) between February 2016 and December 2019 at secondary and tertiary eye care centers. Vessel Skeleton Density (VSD), a measure of capillary density, and Vessel Diameter Index (VDI), a measure of vascular caliber, were calculated from these images. Discriminatory performance of VSD and VDI was evaluated using multivariable logistic regression models predicting DR severity with adjustments for sex, hypertension, and hyperlipidemia. Area under the curve (AUC) was estimated. Model performance was evaluated in two different cohorts. RESULTS: This study included 594 eyes from 385 subjects. Cohort 1 was a training cohort of 509 eyes including 159 control, 155 mild non-proliferative DR (NPDR) and 195 referable DR eyes. Cohort 2 was a validation cohort consisting of 85 eyes including 16 mild NPDR and 69 referable DR eyes. In Cohort 1, addition of VSD and VDI to a model using only demographic data significantly improved the model's AUC for discrimination of eyes with any DR severity from controls (0.91 [95% CI, 0.88-0.93] versus 0.80 [95% CI, 0.76-0.83], p < 0.001) and eyes with referable DR from mild NPDR (0.90 [95% CI, 0.86-0.93] versus 0.69 [95% CI, 0.64-0.75], p < 0.001). The transportability of this regression model was excellent when implemented in Cohort 2 for the referable DR versus mild NPDR comparison. The odds ratio of having any DR compared to control subjects, and referable DR compared to mild DR decreased by 15% (95% CI: 12-18%), and 13% (95% CI: 10-15%), respectively, for every 0.001 unit increase in VSD after adjusting for comorbidities. CONCLUSION: OCTA-derived capillary density has real world clinical value for rapidly assessing DR severity.

Endophthalmitis after intravitreal vascular [corrected] endothelial growth factor antagonists: a six-year experience at a university referral center.

PURPOSE: To assess the rate of infectious endophthalmitis and to describe the clinical and microbiological features of eyes that develop clinically suspected endophthalmitis after an intravitreal injection of vascular endothelial growth factor antagonists. METHODS: The medical records of patients undergoing intravitreal injections of anti-vascular endothelial growth factor agents from January 1, 2005, through December 31, 2010, at a single university referral center and associated satellite clinics were retrospectively analyzed to determine the rate of infectious endophthalmitis after intravitreal anti-vascular endothelial growth factor injections. RESULTS: Twelve cases (11 patients) of clinically suspected endophthalmitis were identified after a total of 60,322 injections (0.02%; 95% confidence interval, 0.0114%-0.0348%). Of the 12 cases, 11 presented within 3 days of the injection. Of the 7 culture-positive cases, 5 were because of Streptococcus species. In 4 of the 5 Streptococcus cases, final visual acuity was hand motions or worse. The rate of clinically suspected endophthalmitis was 0.018% after bevacizumab and 0.027% after ranibizumab injections. CONCLUSION: A very low rate of endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor agents was observed. Patients typically presented within 3 days of injection. Streptococcus species was the most common bacteria isolated, and it was generally associated with poor visual outcomes.

FAILED LASER RETINOPEXY IN A PATIENT UNDERGOING PAZOPANIB THERAPY.

PURPOSE: To report a case of failed endolaser retinopexy in patient taking pazopanib and possible association with impaired retinal remodeling. METHODS: Case report. RESULTS: A 68-year-old man with a history of radiation-induced high-grade metastatic mediastinal leiomyosarcoma, on pazopanib 600 mg daily, presented with a superior retinal tear 2 months after initiating pazopanib. The patient was treated with pars plana vitrectomy and endolaser retinopexy without any immediate complications. One month postoperatively, the patient was found to have a new superior macula-sparing rhegmatogenous retinal detachment extending through the laser barricade nasally. A large proportion of the laser lesions in this area had notably remained chalk-white. The patient underwent pars plana vitrectomy with scleral buckling, and repeat endolaser retinopexy. Pazopanib therapy was stopped 1 week later in consultation with the oncology team and was reinitiated after the retina seemed stable under silicone oil for several weeks. The scars from the patient's repeat endolaser retinopexy remained pale white at his clinic visit 2 months after the procedure, and at that time, his initial laser scars had only just begun to darken with pigment. Four and a half months after the initial vitrectomy and endolaser retinopexy, and three and a half months after his repeat vitrectomy and endolaser retinopexy, all the patient's laser scars have developed increased pigment, and his retina remains completely flat under silicone oil tamponade. CONCLUSION: Pazopanib may have had an adverse effect on retinal wound healing after vitrectomy with endolaser retinopexy, leading to persistence of pale laser lesions many weeks after laser application. It is possible that this may have impaired the typical development of chorioretinal laser scar formation and led to subsequent retinal detachment.

Increasing Incidence and Prevalence of Common Retinal Diseases in Retina Practices Across the United States.

BACKGROUND AND OBJECTIVE: To provide an updated estimate of incidence and prevalence of the foremost retinal diseases in the U.S. PATIENTS AND METHODS: Retrospective study of the Vestrum Health Database evaluating eyes with diagnoses of wet or dry age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), branch or central retinal vein occlusion (BRVO; CRVO) from January 2014 to December 2019 across 58 retina practices. RESULTS: Of the 3,086,791 eyes examined, 490,881 (15.9%) had dry AMD, 294,041 (9.5%) wet AMD, 270,703 (8.8%) DME, 254,690 (8.3%) DR without DME, 73,617 (2.4%) BRVO, and 50,670 (1.6%) CRVO. Dry AMD had the highest incidence. These diseases comprised 61.0% of total prevalence and 54.3% of incidence among patients at the retina practices analyzed. CONCLUSIONS: Based on a diverse database, these diseases comprised the majority of U.S. retina practice cases, with increasing annual incidences. AMD is the most common diagnosis, then diabetic eye disease. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:29-36.].

Visual Acuity Outcomes in Patients Receiving Frequent Treatment of Neovascular Age-Related Macular Degeneration in Clinical Practice.

Purpose: This work evaluates dosing frequency with intravitreal antivascular endothelial growth factor (anti-VEGF) agents over 2 years and visual acuity (VA) outcomes in neovascular age-related macular degeneration (nAMD). Methods: This retrospective analysis assesses electronic medical record data (Vestrum Health treatment and outcomes database) of newly diagnosed nAMD in patients who were initiated on intravitreal anti-VEGF treatment at US clinical sites. Eyes were divided into 2 injection frequency subcohorts (≤ 6 or > 6 injections/y); treatment frequency and change in mean VA (Early Treatment Diabetic Retinopathy Study letters) were evaluated. Results: Overall, 8127 of 213 824 eyes met inclusion criteria in year 1 and 4968 in year 2. During year 1, 77% of the eyes received more than 6 injections (n = 6287), the majority of which received injections at the same frequency during year 2. Mean VA gain from baseline at year 1 was lower in the ≤ 6 than > 6 injections/y subcohort (2.2 vs 6.5, P < .001). Decrease in mean VA from the end of year 1 to year 2 was significantly greater for eyes administered 6 or fewer injections in year 2 than those that received more frequent injections, irrespective of the frequency of injections in the first year. Conclusions: In routine clinical practice, most eyes with nAMD that completed at least 1 year of follow-up were treated with more than 6 injections of anti-VEGF agents during the first year of treatment, resulting in better VA gains than eyes treated less frequently during the same period.

Evaluation of Patients Receiving Intravitreal Antivascular Endothelial Growth Factor for Diabetic Macular Edema in Clinical Practice in the United States.

Purpose: We assessed the effect of treatment frequency with intravitreal antivascular endothelial growth factor (anti-VEGF) agents on visual acuity (VA) in diabetic macular edema (DME). Methods: This retrospective analysis assessed electronic medical records of eyes newly diagnosed with DME and treated with an anti-VEGF agent at US clinics using the Vestrum Health (Naperville, Illinois) treatment and outcomes database. Eyes were divided into 2 injection frequency subcohorts (≤ 6 vs > 6 injections/y); treatment frequency and change in mean VA (Early Treatment Diabetic Retinopathy Study letters) were evaluated. Results: Among 155 240 eyes assessed, 3028 met inclusion criteria for analysis in year 1 and 1292 in year 2. During year 1 of treatment, 57% (n = 1725) received > 6 injections; most continued to receive the same injection frequency during year 2. Mean VA gain from baseline at year 1 was lower in the ≤ 6 than in the > 6 injections/year subcohort (3.7 vs 8.0 letters, respectively; P < .001). Mean VA change from the end of year 1 to year 2 for eyes receiving ≤ 6 injections in year 1 generally remained unchanged, irrespective of year 2 dosing frequency. In eyes that received > 6 injections in year 1, mean VA loss was significantly greater for eyes receiving less-frequent dosing in year 2 than in those maintained on > 6 injections. Conclusions: More than 50% of eyes with DME in routine clinical practice that completed at least 1 year of follow-up received > 6 injections of an anti-VEGF agent during the first year, resulting in better VA gains than eyes treated less frequently.

Outcomes in Patients with Diabetic Macular Edema Requiring Cataract Surgery in VISTA and VIVID Studies.

PURPOSE: To evaluate the impact of cataract surgery on visual and anatomic outcomes in patients with diabetic macular edema treated with intravitreal aflibercept injection (IAI) or laser control and who did not require rescue therapy. DESIGN: Post hoc analysis of 2 phase 3 trials, Study of Intravitreal Aflibercept Injection in Patients with Diabetic Macular Edema (VISTA) and Intravitreal Aflibercept Injection in Vision Impairment Due to DME (VIVID). PARTICIPANTS: Fifty-four patients (laser treatment, n = 11; IAI, n = 43) who underwent cataract surgery during the study period. METHODS: In VISTA and VIVID, patients received IAI 2 mg every 4 weeks, IAI 2 mg every 8 weeks after 5 monthly doses, or laser control through week 100. Starting at week 24, if rescue treatment criteria were met, IAI patients received laser therapy, and laser therapy patients received IAI 2 mg every 8 weeks (after 5 monthly doses). Patients who received rescue treatment before cataract surgery were excluded. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in the laser control and pooled IAI groups before and after cataract surgery. RESULTS: The cumulative incidence of cataract surgery did not depend on treatment group assignment (rate ratio, = 1.517; 95% confidence interval, 0.782-2.944; P = 0.2174). At the last study visit before surgery, BCVA was 62.2 and 56.9 letters and CRT was 342 µm and 301 µm in the laser control and IAI groups, respectively. At the first study visit after cataract surgery, BCVA was improved significantly in both the laser control and IAI groups to 73.5 letters (P = 0.010 compared with last visit before surgery) and 67.2 letters (P < 0.001 compared with last visit before surgery), respectively. Corresponding change in CRT was a modest increase to 364 µm (P > 0.05 compared with last visit before surgery) and 359 µm (P = 0.013 compared with last visit before surgery), respectively. CONCLUSIONS: Incidence of cataract surgery was similar in both treatment groups. Despite a modest worsening in CRT after cataract surgery, BCVA was improved in both treatment groups.

Social Cost of Blindness Due to AMD and Diabetic Retinopathy in the United States in 2020.

BACKGROUND AND OBJECTIVE: To estimate the social cost of blindness due to wet age-related macular degeneration (wAMD), diabetic macular edema (DME), and proliferative diabetic retinopathy (PDR) in the United States in 2020. PATIENTS AND METHODS: Excess costs that occur because of blindness were estimated as the difference in costs in blind versus non-blind individuals. Per-patient costs were aggregated using the number of cases of blindness due to wAMD, DME, and PDR projected in 2020. RESULTS: Associated annual excess direct costs, indirect costs, and quality-adjusted life year loss per blind individual were $4,944, $54,614, and 0.214, respectively. Combining estimates with 246,423 projected cases of blindness due to wAMD, DME, and PDR translated to total societal costs of $20 billion in 2020, estimated to triple by 2050. CONCLUSION: Excess social costs associated with blindness in individuals with wAMD, DME, and PDR are substantial, with more than half of the burden attributed to indirect costs. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S6-S14.].

Triamcinolone acetonide preparations: impact of crystal size on in vitro behavior.

PURPOSE: To characterize the in vitro behavior of three preparations of triamcinolone acetonide (TA). METHODS: Three preparations of TA were mixed with Balanced Salt Solution Plus: commercially available TA (Kenalog 40, Bristol-Myers Squibb, Princeton, NJ), compounded preservative-free triamcinolone acetonide (PFTA, New England Compounding Center, Framingham, MA), and triamcinolone acetonide injectable suspension (TAIS, TRIESENCE, Alcon, Inc., Fort Worth, TX). We determined the mean number of crystalline aggregates per high-power deconvolution microscopy field, largest aggregate area, and spectroscopic photometric absorption. RESULTS: Preservative-free triamcinolone acetonide had larger mean number of aggregates compared with TA (time 0 P = 0.002, 10 minutes P < 0.001) and TAIS (time 0 P < 0.001, 10 minutes P = 0.003). Aggregate size varied at both 0 and 10 minutes: TAIS > TA > PFTA. Spectroscopic photometric absorption decreased in direct correlation to aggregate size over time for all three preparations. CONCLUSION: In vitro, PFTA in Balanced Salt Solution Plus had more aggregates of smaller size than either TA or TAIS. By contrast, TAIS had much larger aggregate size than both PFTA and TA, and this increased over time. These findings correlate with the clinical observations that PFTA and TA tend to disperse throughout the vitreous, whereas TAIS tends to conglomerate and gravitate toward the most dependent portion of the eye in a globular fashion.