SGLT2 inhibitors and diabetic retinopathy progression.

PURPOSE: To evaluate whether sodium-glucose co-transporter 2 (SGLT2) inhibitors affect progression of non-proliferative diabetic retinopathy (NPDR) compared to standard of care. METHODS: A retrospective cohort study compared subjects enrolled in a commercial and Medicare Advantage medical claims database who filled a prescription for a SGLT2 inhibitor between 2013 and 2020 to unexposed controls, matched up to a 1:3 ratio. Patients were excluded if they were enrolled for less than 2 years in the plan, had no prior ophthalmologic exam, had no diagnosis of NPDR, had a diagnosis of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), had received treatment for vision-threatening diabetic retinopathy (VTDR), or were younger than 18 years. To balance covariates of interest between the cohorts, an inverse probability treatment weighting (IPTW) propensity score for SGLT2 inhibitor exposure was used. Multivariate Cox proportional hazard regression modeling was employed to assess the hazard ratio (HR) for VTDR, PDR, or DME relative to SGLT2 exposure. RESULTS: A total of 6065 patients who initiated an SGLT2 inhibitor were matched to 12,890 controls. There were 734 (12%), 657 (10.8%), and 72 (1.18%) cases of VTDR, DME, and PDR, respectively, in the SGLT2 inhibitor cohort. Conversely, there were 1479 (11.4%), 1331 (10.3%), and 128 (0.99%) cases of VTDR, DME, and PDR, respectively, among controls. After IPTW, Cox regression analysis showed no difference in hazard for VTDR, PDR, or DME in the SGLT2 inhibitor-exposed cohort relative to the unexposed group [HR = 1.04, 95% CI 0.94 to 1.15 for VTDR; HR = 1.03, 95% CI 0.93 to 1.14 for DME; HR = 1.22, 95% CI 0.89 to 1.67 for PDR]. CONCLUSION: Exposure to SGLT2 inhibitor therapy was not associated with progression of NPDR compared to patients receiving other diabetic therapies.

Statin use and the risk of progression to vision threatening diabetic retinopathy.

PURPOSE: This study aims to assess the effect of statins on progression from nonproliferative diabetic retinopathy (NPDR) to vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME). METHODS: Two cohort studies using a U.S. medical claims database from 2002 to 2019 including NPDR patients 18 years or older. A risk factor analysis performed a time-updating cox regression model assessing statin usage. A second new-user active comparator design analysis replicating a previously published study. Main outcomes included a new diagnosis of VTDR (composite of either PDR or DME) or DME and PDR individually for the risk factor study and included additional outcomes of new DR, NPDR, vitreous hemorrhage (VH) and tractional retinal detachment (TRD) for the new user study. RESULTS: Risk factor analysis included 66 617 statin users with NPDR at baseline and 83 365 nonstatin users. Of these, 27 325 (18.2%) progressed to VTDR, 4086 (2.71%) progressed to PDR, and 22 750 (15.1%) progressed to DME. After multivariable analysis, no protective effect of statin use was found for progression to VTDR, PDR, or DME (HR = 1.01-3, p >0.33 for all comparisons). Replicated new user design analysis also showed no protective effect for statins on risk of development of DR (HR = 1.03, 95% CI: 0.99-1.07, p = 0.13), PDR (HR = 0.89, 95% CI: 0.79-1.02, p = 0.09), DME (HR = 0.94, 95% CI: 0.86-1.03, p = 0.21), VH (HR = 1.00, 95% CI: 0.86-1.16, p = 0.99), and TRD (HR = 1.11, 95% CI: 0.89-1.38, p = 0.36). CONCLUSION: Statin use was found not to be protective for progression of DR regardless of study methodology. These results suggest that the specifics of the population studied rather than differing study methodology are important in assessing the effect of statins on DR progression.

Demographic and Clinical Characteristics Associated with Minimally Invasive Glaucoma Surgery Use: An Intelligent Research in Sight (IRIS®) Registry Retrospective Cohort Analysis.

PURPOSE: Minimally invasive glaucoma surgery (MIGS) is increasingly performed at the time of cataract extraction. Understanding the demographic and clinical characteristics of patients undergoing MIGS procedures may provide insight into patient selection. This study evaluates racial-ethnic and other differences in the use of MIGS in persons with cataract and open-angle glaucoma (OAG). DESIGN: Retrospective cohort study using Intelligent Research in Sight (IRIS) Registry data. PARTICIPANTS: Patients aged ≥ 40 years with a diagnosis of OAG and no history of MIGS or cataract surgery who were undergoing cataract extraction, with or without MIGS, during 2013 to 2017 in the United States. METHODS: Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: Variables assessed include age, sex, race-ethnicity, disease severity, insurance type, census region, comorbidity, and cup-to-disc ratio (CDR). RESULTS: The odds of MIGS use was greater among patients who were aged ≥ 60 years (OR, 1.10 [95% CI, 1.05-1.16]); Black (OR, 1.11 [CI, 1.07-1.15]) compared with White; a Medicare recipient (OR, 1.12 [CI, 1.10-1.15]) versus privately insured; or in the Midwest (OR, 1.32 [CI, 1.28-1.36]) or Northeast (OR, 1.26 [CI, 1.22-1.30]) compared with the South. Having moderate rather than mild glaucoma (OR, 1.07 [CI, 1.04-1.11]) and a higher CDR (OR for 0.5 to 0.8 vs. <0.5, 1.24 [CI, 1.21-1.26]; OR for >0.8 to 1.0 vs. <0.5, 1.27 [CI, 1.23-1.32]) were also each associated with increased odds of MIGS use. Use of MIGS was less likely in women (OR, 0.96 [CI, 0.94-0.98]); patients taking 5 to 7 glaucoma medications (OR, 0.94 [CI, 0.90-0.99]) compared with 1 to 2 medications; and patients with severe, compared with mild, glaucoma (OR, 0.64 [CI, 0.61-0.67]). CONCLUSIONS: This analysis highlights the importance of capturing race-ethnicity data and other pertinent patient characteristics in electronic health records to provide insight into practice patterns. Such data can be used to assess the long-term performance of MIGS and other procedures in various patient populations.

Visit adherence and visual acuity outcomes in patients with diabetic macular edema: a secondary analysis of DRCRnet Protocol T.

PURPOSE: To quantify the association between visit adherence and visual acuity (VA) in diabetic macular edema (DME). METHODS: This secondary analysis of the 2-year DRCRnet Protocol T study of 656 patients required one visit every 4 weeks in the first year, then at variable 4-16-week intervals in the second year. Visit adherence measured as number of missed visits, average (avg days) and longest (max days) visit interval, average (avg missed days) and longest (max missed days) unintended visit interval, and visit constancy (percentage of 3-month periods with at least 1 visit). Avg and max missed days were categorized as on time (0 days), late (> 0-60 days), and very late (> 60 days). Primary outcome was change in ETDRS VA between baseline study visit and last attended visit, using multivariate linear regression models controlling for age, gender, race, ethnicity, treatment arm, baseline VA, hemoglobin A1c, insulin use, and number of lasers and injections. RESULTS: Mean number of missed visits was 1.7. 616 (94%) patients had 100% visit constancy. A total of 331 (51%) patients were on time, 171 (26%) late, and 154 (23%) very late in avg missed days. Max missed days ranged 0-696 days. Adjusted, each missed visit was associated with 0.3-letter decrease (95%CI - 0.6, - 0.1, p = 0.02); being very late in avg and max missed days saw - 4.2 letters (95%CI - 6.4, - 2.0, p < 0.001) and - 4.0 letters (95%CI - 6.1, - 1.9, p < 0.001), respectively, than on time. Those that averaged > 4 days missed per attended visit saw 4.6 letters worse (95%CI - 7.3, - 2.0, p < 0.001). CONCLUSIONS: Visit adherence is associated with visual acuity outcomes in DME patients.

Decreased risk of non-infectious anterior uveitis with statin therapy in a large healthcare claims database.

PURPOSE: The purpose of this study is to determine if statin therapy decreases the incidence of non-infectious uveitis (NIU) using a retrospective cohort study. METHODS: Patients enrolled in a national insurance plan who initiated statin (n = 711,734, statin cohort) or other lipid-lowering therapy (n = 148,044, non-statin cohort) were observed for NIU development. Incident NIU in the primary analysis was defined as a new diagnosis code for NIU followed by a second instance of a NIU code within 120 days. For the secondary outcome definition, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the NIU diagnosis code was used instead of the second NIU diagnosis code. Estimation of NIU incidence used multivariable Cox proportional hazards regression. The proportional hazards assumption was satisfied by creating two time periods of analysis, ≤ 150 and > 150 days. Subanalyses were performed by anatomic subtype. RESULTS: Overall, the primary outcome occurred 541 times over 690,465 person-years in the statin cohort and 103 times over 104,301 person-years in the non-statin cohort. No associations were seen in the ≤ 150-day analyses (p > 0.20 for all comparisons). However, after 150 days, the statin cohort was less likely to develop any uveitis [hazard ratio (HR) = 0.70, 95% confidence interval (CI): 0.51-0.97, P = 0.03] in the primary outcome analysis, but did not meet significance for the secondary outcome (HR = 0.85, 95% CI: 0.63-1.15, P = 0.30). Similarly, in the anatomic subtype analysis, after 150 days, the statin cohort was less likely to develop anterior uveitis (HR = 0.67, 95% CI: 0.47-0.97, P = 0.03) in the primary analysis, but the association did not reach significance for the secondary outcome (HR = 0.82, 95% CI: 0.56-1.20, P = 0.31). CONCLUSION: Our results suggest that statin therapy for > 150 days decreases the incidence of NIU.

SYSTEMIC MEDICATION USE AND THE INCIDENCE AND GROWTH OF GEOGRAPHIC ATROPHY IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENTS TRIALS.

PURPOSE: To determine associations of systemic medications with the incidence and growth of geographic atrophy (GA) in participants of the comparison of age-related macular degeneration treatments trials. METHODS: Participants of comparison of age-related macular degeneration treatments trials with new untreated choroidal neovascularization in the study eye (one study eye per participant) were randomized to receive treatment with bevacizumab or ranibizumab. Participants were released from clinical trial treatment at 2 years and examined at approximately 5 years. Color fundus photographs and fluorescein angiograms taken at baseline, Years 1, 2, and 5 were assessed for the presence and size of GA by two masked graders. Participants were interviewed about systemic medication use at baseline. Systemic medications previously reported to be associated with age-related macular degeneration were evaluated for associations with GA incidence in study eye using univariable and multivariable Cox models and for association with the GA growth using linear mixed effects models. RESULTS: In multivariable analysis of 1,011 study eyes without baseline GA, systemic medications, including cholinesterase inhibitors, angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, diuretics, aspirin, steroids, statins, hormone replacement therapy, antacids, and drugs targeting G protein-coupled receptors, were not associated with GA incidence in the study eye (all adjusted hazard ratios ≤1.86, P ≥ 0.18). In multivariable analysis of 214 study eyes with longitudinal GA size measurements, calcium channel blockers were associated with a higher GA growth rate (0.40 vs. 0.30 mm/year, P = 0.02). CONCLUSION: None of the systemic medications analyzed were associated with GA incidence. However, calcium channel blockers were associated with a higher growth rate of GA in the study eye.

Risk of Noninfectious Uveitis with Female Hormonal Therapy in a Large Healthcare Claims Database.

PURPOSE: To determine if female hormonal therapy (FHT) increases the incidence of noninfectious uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Women exposed to FHT and matched women unexposed to FHT enrolled in a national insurance plan. METHODS: Estimation of noninfectious uveitis incidence used multivariable Cox proportional hazards regression. To account for differences between the exposed and unexposed cohorts, a propensity score for being prescribed FHT was created using logistic regression, and inverse probability of treatment weighting was performed. MAIN OUTCOME MEASURES: Incidence of noninfectious uveitis. For the primary outcome, incident noninfectious uveitis was defined as a new diagnosis code for noninfectious uveitis followed by a second instance of a noninfectious uveitis code within 120 days. For the alternative outcome definition, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the uveitis diagnosis code was used instead of the second uveitis diagnosis code. RESULTS: There were 217 653 women exposed to FHT and 928 408 women not unexposed to FHT. For the primary outcome, the hazard ratio (HR) for incident noninfectious uveitis was not significantly different between the FHT and unexposed cohorts (HR, 0.99; 95% confidence interval [CI], 0.83-1.17; P = 0.87). With the alternative outcome definition, the FHT cohort was more likely to develop uveitis (HR, 1.21; 95% CI, 1.04-1.41; P = 0.01). When examined by anatomic subtype, for anterior uveitis there was a greater likelihood of incident uveitis in the exposed cohort (HR, 1.23; 95% CI, 1.05-1.45; P = 0.01) for the alternative outcome definition but not for the primary outcome. With age stratification, women exposed to FHT aged ≥45 years at the time of FHT prescription were more likely to develop uveitis (HR, 1.23; 95% CI, 1.03-1.47; P = 0.03) for the alternative outcome definition. A similar HR (1.22) was seen for women aged ≤44 years at the time of prescription, but this association did not meet statistical significance (P = 0.20). CONCLUSIONS: Exposure to FHT increases the rate of incident noninfectious uveitis when uveitis is defined on the basis of both diagnostic codes and documentation of corticosteroid treatment. However, the risk is modest and FHT is likely safe with regard to noninfectious uveitis risk in the majority of patients exposed to these drugs.

Repeated intravitreal injections of antivascular endothelial growth factors and risk of intraocular pressure medication use.

PURPOSE: To determine the risk of initiating ocular hypertension and glaucoma treatment with repeated injections of antivascular endothelial growth factors (anti-VEGF). METHODS: A unique, retrospective cohort study was performed using a large national US medical claim database. The study population included patients who had 1 or more injections of an anti-VEGF agent. Exclusion occurred for any previous glaucoma, glaucoma suspect, glaucoma-related procedure, an ocular steroid injection, or not seeing an eye care provider at least once in each year of follow-up. Cohorts were divided into quartiles based on the number of injections performed over the follow-up period. Patients were observed for 2 and 3 years. The main outcome measure was defined as any new prescription for an ocular antihypertensive medication with a concurrent diagnosis of glaucoma, glaucoma suspect, or ocular hypertension. Multivariate logistic regression determined the odds of initiating glaucoma treatment in each injection quartile while controlling for numerous covariates. Sensitivity analysis assessed outcomes that included new medication only as well as a new medication plus diagnosis of glaucoma. RESULTS: In total, 17,113 and 9992 patients met 2- and 3-year observation end points, respectively. The multivariate odds ratio for initiating glaucoma treatment at 2 years was higher in the highest quartile (OR 1.96, 95% CI 1.39-2.76, p < 0.001) compared with the lowest. The 3-year comparison had similar results with increased odds in the highest quartile (OR 1.51, 95% CI 1.07-2.13, p = 0.006) compared with the lowest. Sensitivity analyses also showed similar results with more injections being associated with initiating treatment (p < 0.053 for all comparisons). CONCLUSIONS: Repeated anti-VEGF injections are associated with an increased odds of initiating treatment for ocular hypertension and glaucoma.

SYSTEMIC BETA-BLOCKERS AND RISK OF PROGRESSION TO NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine whether oral beta-blockers (BBs) are associated with the development of neovascular age-related macular degeneration (nAMD). METHODS: Retrospective cohort study of patients from 2000 to 2014 using data from a large national U.S. insurer's administrative medical claims database. Patients with nonexudative AMD who initiated (index date) BB, a calcium channel blocker (CCB), an angiotensin-converting enzyme/angiotensin receptor blocker, or a diuretic. Patients were excluded for <2 years in the plan before the index date, any history of nAMD or diagnosis, or treatment for an ocular disease that could be confused with nAMD. Hazard of developing of nAMD was the main outcome measure. Primary analysis compared BB with CCB patients with BB versus the other classes as secondary analyses. In addition, a sensitivity analysis was performed between BB and CCB cohorts using 1:1 propensity score matching. Cox proportional hazard regression was performed to estimate the hazard ratio (HR) of developing nAMD at 90, 180, and 365 days for BB. Covariates of interest included demographic information, year of index date, number of antihypertensive medications, and other comorbid systemic conditions. RESULTS: Eighteen thousand seven hundred and fifty-four BB patients and 12,784 CCB patients met criteria for inclusion. After controlling for covariates, patients on BB had a lower hazard for nAMD at both 90 and 180 days than patients on CCB (HRs: 0.67-0.71; P < 0.01 for both) and diuretics (HRs: 0.55-0.62; P < 0.01). Patients on BB versus angiotensin-converting enzyme/angiotensin receptor blocker at all time points and BB versus CCB and diuretics at 365 days did not have a significantly lower association with nAMD (HR: 0.73-0.85; P > 0.06 for all comparisons). A sensitivity analysis using propensity score matching yielded similar results with patients on BB significantly less likely to develop nAMD at 90 and 180 days (HR: 0.70-0.76; P < 0.049 for both) but not at 365 days (HR: 0.88; P = 0.30) compared with patients on CCB. CONCLUSION: No evidence was found that BB usage increased the hazard for nAMD relative to other antihypertensive medications.

COMPARATIVE RISK OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION WITH BEVACIZUMAB, AFLIBERCEPT, AND RANIBIZUMAB.

PURPOSE: To determine whether sterile preloading of anti-vascular endothelial growth factor agents reduces the risk of postintravitreal injection endophthalmitis. METHODS: This is a retrospective cohort study using medical claims data from a large, national US insurer. Cohorts were created using intravitreal injections of anti-vascular endothelial growth factor injections from 2005 to 2016. For inclusion, patients had to have at least 6 months of data before the injection and were excluded for any previous diagnosis of endophthalmitis, multiple injected drugs on the day of injection, or intraocular surgery within 15 days of the injection or between an injection and a diagnosis of endophthalmitis. The primary outcome was the odds of endophthalmitis after an intravitreal injection. RESULTS: A total of 706,725 bevacizumab, 210,849 ranibizumab, and 177,731 aflibercept injections were given to 130,327 patients. Multivariate analysis showed that ranibizumab and aflibercept together had an increased odds of endophthalmitis (odds ratio = 1.29, 95% confidence interval: 1.04-1.59, P = 0.02) compared with bevacizumab. Individually, ranibizumab (odds ratio = 1.25, 95% confidence interval: 0.97-1.61, P = 0.08) and aflibercept (odds ratio = 1.34, 95% confidence interval: 0.99-1.81, P = 0.06) each had higher odds of endophthalmitis, but neither result met significance. Also, when compared with male patients, female patients had a higher odds of getting endophthalmitis (odds ratio: 1.30, 95% confidence interval: 1.05-1.61, P = 0.02). CONCLUSION: The odds of endophthalmitis with aflibercept and ranibizumab combined were higher compared with the sterilely preloaded bevacizumab, arguing for a safety advantage of sterile preloading of anti-vascular endothelial growth factor injections.

TESTOSTERONE SUPPLEMENTATION AND RETINAL VASCULAR DISEASE.

PURPOSE: To determine whether testosterone supplementation is associated with retinal artery occlusion (RAO) or retinal vein occlusion (RVO). METHODS: Retrospective matched cohort study using data from a large national U.S. insurance database. The testosterone cohort consisted of all male patients who filled a prescription for testosterone from 2000 to 2013. Five controls were matched on age (±3 years), sex, race, and similar time in plan (±3 months) for every exposed patient. Exclusion occurred for <2 years in the plan, <1 eye care visit, medications known to affect androgen levels, and systemic diseases associated with occlusions or increased testosterone. Cox proportional hazard regression assessed the hazard of a new diagnosis of RAO or RVO while controlling for age, race, diabetes mellitus, and hypertension. RESULTS: A total of 35,784 incident testosterone users were compared with 178,860 matched controls. Ninety-three (0.3%) RAOs and 50 (0.1%) RVOs were found in the testosterone cohort and contrasted with 316 (0.2%) RAOs and 232 (0.1%) RVOs in the control group. After multivariate analysis, testosterone supplementation significantly increased the hazard of RAO (hazard ratio: 1.43, 95% confidence interval: 1.12-1.81, P = 0.004), but not of RVO (hazard ratio: 1.03, 95% confidence interval: 0.74-1.42, P = 0.86). CONCLUSION: Although the incidence of RAO and RVO is low in users of testosterone, supplementation therapy is associated with an increased hazard of RAO, but apparently not of RVO.

SYSTEMIC BETA-BLOCKERS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate whether oral beta-blockers (BBs) are associated with a decreased number of intravitreal injections in patients with incident neovascular age-related macular degeneration. METHODS: A retrospective cohort study of subjects with a new diagnosis of neovascular age-related macular degeneration was conducted using a medical claims database from a large national US insurer. Two cohorts were created for comparison consisting of patients with regular use of BBs or calcium channel blockers. The main outcome measured was the difference in the mean number of intravitreal injections administered between the two cohorts. RESULTS: After inclusion and exclusion criteria, 239 BB and 155 calcium channel blocker subjects remained for analysis. Univariate analysis revealed that the mean number of injections in the BB cohort was 6.43 (95% confidence interval [CI] 5.90-6.95) versus 6.55 (95% CI 5.85-7.25) in the calcium channel blocker cohort (P = 0.78). After multivariate adjustment, the mean number of injections in the BB group was 6.32 (95% CI 5.77-6.87) versus 6.71 (95% CI 6.02-7.40) in the calcium channel blocker group. The overall difference between the 2 groups was -0.39 (95% CI difference -1.29 to 0.51; P = 0.40). CONCLUSION: The use of oral BBs is not associated with a decreased number of intravitreal injections in incident neovascular age-related macular degeneration patients.

The Association between Intravitreal Steroids and Post-Injection Endophthalmitis Rates.

PURPOSE: To determine whether there is a difference in the risk of endophthalmitis after an intravitreal steroid injection compared with an anti-vascular endothelial growth factor (VEGF) agent injection. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 75,249 beneficiaries in a large national US medical claims database representing 406 380 intravitreal injections. METHODS: Data were searched for all intravitreal injections (Current Procedural Terminology 67028) performed between 2003 and 2012. Cohorts were created on the basis of injections using anti-VEGF agents (bevacizumab, ranibizumab, aflibercept, and pegaptanib) and intraocular steroids (triamcinolone and dexamethasone). Endophthalmitis was defined as having a new endophthalmitis diagnosis (International Classification of Diseases 9th Revision 360.0x) and a "tap-and-inject" procedure (Current Procedural Terminology 67015, 67025), a vitrectomy (67036), or an intravitreal antibiotic injection on the same day, between 1 and 14 days post-injection. Exclusion occurred for any history of endophthalmitis, <6 months in the plan, or <1 month follow-up. The main outcome measure was the odds of endophthalmitis using logistic regression while controlling for injection-associated diagnosis, age, race, and gender. RESULTS: A total of 387,714 anti-VEGF injections and 18 666 steroid intravitreal injections were performed and followed by 73 (rate=0.019% or 1/5283 anti-VEGF injections) and 24 (rate=0.13% or 1/778 steroid injections) cases of endophthalmitis, respectively. After controlling for diagnosis, age, race, and gender, the odds ratio (OR) for endophthalmitis occurring was 6.92 (95% confidence interval, 3.54-13.52, P<0.001) times higher post-steroid injection compared with anti-VEGF injections. CONCLUSIONS: The rate of endophthalmitis post-intravitreal steroid injection in a national cohort was 0.13% (1/778 injections). This rate conferred a significantly increased OR of 6.92 for endophthalmitis compared with anti-VEGF agents.

Outcomes, impact on management, and costs of fungal eye disease consults in a tertiary care setting.

OBJECTIVE: To determine the frequency of clinical management changes resulting from inpatient ophthalmic consultations for fungemia and the associated costs. DESIGN: Retrospective case series. PARTICIPANTS: Three hundred forty-eight inpatients at a tertiary care center between 2008 and 2012 with positive fungal blood culture results, 238 of whom underwent an ophthalmologic consultation. METHODS: Inpatient charts of all fungemic patients were reviewed. Costs were standardized to the year 2014. The Student t test was used for all continuous variables and the Pearson chi-square test was used for categorical variables. MAIN OUTCOME MEASURES: Prevalence of ocular involvement, rate of change in clinical management, mortality rate of fungemic patients, and costs of ophthalmic consultation. RESULTS: Twenty-two (9.2%) of 238 consulted patients with fungemia had ocular involvement. Twenty patients had chorioretinitis and 2 had endophthalmitis. Only 9 patients (3.7%) had a change in management because of the ophthalmic consultation. One patient underwent bilateral intravitreal injections. Thirty percent of consulted patients died before discharge or were discharged to hospice. The total cost of new consults was $36 927.54 ($204.19/initial level 5 visit and $138.63/initial level 4). The cost of follow-up visits was $13 655.44 ($104.24/visit). On average, 26.4 patients were evaluated to find 1 patient needing change in management, with an average cost of $5620.33 per change in 1 patient's management. CONCLUSIONS: Clinical management changes resulting from ophthalmic consultation in fungemic patients were uncommon. Associated costs were high for these consults in a patient population with a high mortality rate. Together, these data suggest that the usefulness of routine ophthalmic consultations for all fungemic patients is likely to be low.

Risk of retinal tear or detachment with oral fluoroquinolone use: a cohort study.

PURPOSE: The aim of this study is to determine if oral fluoroquinolone exposure is associated with an increased hazard for having a retinal tear or detachment. METHODS: A retrospective cohort study was performed using individuals who met inclusion criteria from The Health Improvement Network database. Cohorts were created for individuals who had a prescription written for either an oral fluoroquinolone or an oral ß-lactam antibiotic (comparison group). Subjects were excluded if they had a previous diagnosis of a retinal tear or detachment (hereafter retinal break (RB)), or a procedure code to treat an RB, where in the practice for less than 365 days, had a previous prescription for either antibiotic within 365 days of the index date or had intraocular surgery or a diagnosis of endophthalmitis within 90 days prior to the antibiotic prescription. Covariates of interest were age, gender, diabetes, and year of index. The primary outcome measure of interest was the hazard ratio (HR) of undergoing a procedure to treat an RB within 7, 30, 90, or 365 days after exposure to an oral fluoroquinolone prescription versus an oral ß-lactam prescription. RESULTS: After exclusions, 6,604,423 prescriptions (290,393 fluoroquinolone; 6,314,030 ß-lactam) from 3,413,498 patients (247,073 fluoroquinolone; 3,303,641 ß-lactam) and 2685 RB procedures were eligible for analysis (661 retinal tears and 2024 retinal detachments). For fluoroquinolones, 0, 1, 5, and 23 RBs occurred at the 7-, 30-, 90-, and 365-day time points, respectively. For ß-lactam prescriptions, 7, 28, 87, and 373 RBs occurred at the 7-, 30-, 90-, and 365-day time points, respectively. Because of zero events occurring in the fluoroquinolone cohort during the 7-day observation period, an unadjusted or an adjusted HR (and subsequent p-value or confidence intervals) was unable to be calculated. Univariate and multivariate analyses demonstrated that fluoroquinolones were not significantly associated with RB in the 30-, 90-, or 365-day observation periods (30-day HR = 0.78, p = 0.80, 95%CI: 0.11, 5.71; 90-day HR = 1.25, p = 0.63, 95%CI: 0.51, 3.08; and 365-day HR = 1.35, p = 0.16, 95%CI: 0.89, 2.06). CONCLUSIONS: Our results do not support an association between oral fluoroquinolone use and subsequent procedures to treat an RB.

Volume and composition of reflux after intravitreal injection.

PURPOSE: To quantify the amount of drug loss from cadaveric human eyes, which are injected via the pars plana with a known volume of dye at variable intraocular pressures. METHODS: Eight cadaver eyes were divided into 2 intraocular pressure groups: normal (15 mmHg; 4 eyes) or high (30 mmHg; 4 eyes). Each eye was injected with 50 µL of hematoxylin dye, and the subsequent reflux was immediately collected on a Schirmer's test strip. The test strip was scanned and digitally analyzed to determine the area of saturation and total color intensity present. Using a previously established equation, total volume of reflux and the amount of dye within that reflux were calculated. RESULTS: The average total volume of refluxed fluid was 1.68 µL (median, 0.62 µL), with a range of 0 µL to 8.05 µL. The average volume of refluxed dye was 0.37 µL (median, 0.08 µL), with a range of 0 µL to 2.15 µL. On average, only 0.74% of the original 50 µL of injected dye was lost (median, 0.15%), with a range from 0% to 4.30%. CONCLUSION: Although the presence of subconjunctival bleb formation after intravitreal injection may be a concern to the clinician, data from the present study shows that only a very small amount of the injected therapeutic agent is lost in the reflux.

Risk Factors for Chalazion Diagnosis and Subsequent Surgical Excision.

PURPOSE: To identify factors associated with chalazion diagnosis and surgical excision. METHODS: Patients with an incident chalazion diagnosis from 2002 to 2019 were compared 1:5 with matched controls. Multivariable logistic regression was performed to identify variables associated with diagnosis and surgical excision. RESULTS: Chalazion patients (n = 134,959) and controls (678,160) were analyzed. Risk factors for diagnosis included female sex, non-white race, northeast location, conditions affecting periocular skin and tear film (blepharitis, meibomian gland dysfunction, rosacea, pterygium), non-ocular inflammatory conditions (gastritis, inflammatory bowel disease, sarcoidosis, seborrheic dermatitis, Graves' disease), and smoking (p < .001 for all comparisons). Thirteen percent of patients with chalazion underwent subsequent surgical excision. Diabetes and systemic sclerosis diagnoses decreased odds of diagnosis (p < .001). Male sex, rosacea diagnosis, Black and Hispanic race, antibiotic use, and doxycycline use increased odds of surgery (p < .001). CONCLUSION: Female sex, non-white race, conditions affecting periocular skin and the tear film, several non-ocular inflammatory conditions, and smoking were risk factors for chalazion diagnosis. Male sex, rosacea diagnosis, Black and Hispanic race, antibiotic use, and doxycycline use were risk factors for surgical intervention for chalazion. Our results prompt further study of these variables and their relationship to chalazion diagnosis to understand physiology and improve clinical outcomes. Furthermore, the results of this study suggest early recognition and treatment of concomitant rosacea may serve an important role in the management of chalazion and in the prevention of surgical intervention.

Real-world socioeconomic determinants of corneal crosslinking in a national cohort.

PURPOSE: To characterize recent socioeconomic trends in patients with keratoconus/corneal ectasias undergoing corneal crosslinking (CXL). SETTING: A deidentified administrative medical claims database comprised commercial and Medicare Advantage health claims from across the United States. DESIGN: Population-based retrospective cohort study. METHODS: This study identified 552 patients with keratoconus/corneal ectasia who underwent CXL and 2723 matched controls who did not undergo CXL based on Current Procedural Terminology coding from a U.S. national insurance claims database from 2016 to 2020. For each patient, characteristics, including sex, race, age, household net worth, education level, insurance plan type, and geographic region, were extracted. Multivariate logistic regression was conducted to determine the odds of undergoing crosslinking. RESULTS: Age 30 years or older (odds ratio [OR], 0.34, P < .001) was associated with decreased likelihood of undergoing CXL. Sex, race, education, and patient income were not associated with odds of undergoing CXL. Patients with health maintenance organization insurance had lower odds of undergoing CXL (OR, 0.64, P = .047). Geographically, patients on the east coast (OR, 0.37, P < .001) and Lower Midwest (OR, 0.31, P < .001) had statistically lower odds of undergoing crosslinking. CONCLUSIONS: This is the first study to identify socioeconomic determinants of CXL, and it highlights that geographic location and insurance type may limit accessibility to patients.