Hydroxychloroquine: balancing the need to maintain therapeutic levels with ocular safety: an update.

PURPOSE OF REVIEW: Antimalarial drugs including chloroquine, its less toxic quinolone-derivative hydroxychloroquine (HCQ), and quinacrine have become cornerstones in the treatment of autoimmune diseases including systemic lupus, rheumatoid arthritis, sarcoidosis, and Sjogren syndrome; cutaneous disorders, antiphospholipid syndrome, and have recently been employed at higher dioses in oncology. Benefits include anti-inflammatory effects, protection against thrombosis, and improved control of hyperglycemia and hyperlipidemia. In general, both the therapeutic advantages and the toxic effects of the drugs correlate with the dose and the duration of therapy. Here we summarize the current literature regarding the administration and the safety profile of HCQ in management of rheumatologic disease and focus on the most recent revised American Academy of Ophthalmology (AAO) guidelines for prevention and detection of hydroxychloroquine retinopathy to help guide therapeutic decision-making for patients. RECENT FINDINGS: The risk of antimalarial-induced retinal toxicity is better predicted by calculating the daily dosage based on 5 mg/kg total body weight rather than 6.5 mg/kg lean body weight and reducing dosage in patients with risk factors such as renal failure. The risk of retinal toxicity after 5 years is substantially increased even when these guidelines are followed; hence dose reduction is appropriate with long-term use. Newer techniques provide improved detection of early signs of retinal damage. These advances are reflected in the revised AAO guidelines 2016, which are in part based on the retrospective study by Melles and Marmor of HCQ toxicity. SUMMARY: The most important changes in practice guidelines include dose calculation based on total body weight, dose reduction after long-term use, and intensified screening with techniques including optical coherence tomography (OCT) after 5 years.

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.

Psychosocial Effects of Remote Reading with Telephone Support versus In-Person Health Education for Diverse, Older Adults.

This study evaluated initial information about psychosocial differences of 130 diverse, older adults (M age: 70.8 ± 9.2 years) who received a "low-tech" remote (independent reading with telephone support) or in-person education through DREAMS (Developing a Research Participation Enhancement and Advocacy Training Program for Diverse Seniors) health seminar series. Outcomes on measures of depression, quality of life, and spatial extent of lifestyle of 115 completers were analyzed at baseline, immediately post-intervention, and 8-week follow-up. Adjusted at baseline, psychosocial outcomes were compared between groups at post-test and 8-week follow-up using adjusted mean differences. Post-participation, compared to remote participants, in-person participants had significantly lower depression on Beck Depression Inventory-II, Geriatric Depression Scale, and significantly higher mental quality of life on Short Form-12. This study links knowledge acquisition via in-person learning with decreased stress, depression, and increased quality of life among seniors. Identifying effective educational delivery methods may increase clinical research involvement for aging communities.

Remote versus In-Person Health Education: Feasibility, Satisfaction, and Health Literacy for Diverse Older Adults.

OBJECTIVES: Health education may improve health in geriatric patients. To evaluate differences between remote and in-person education, the DREAMS (Developing a Research Participation Enhancement and Advocacy Training Program for Diverse Seniors) health seminar series compared in-person and remote learning groups to assess feasibility, satisfaction, adherence, health literacy, and cognitive outcomes. RESEARCH DESIGN: Nonrandomized two-arm interventions occurred remotely or in-person. About 130 diverse, older adults (M age: 70.8 ± 9.2 years; in-person n = 95; remote, n = 35) enrolled. Data from 115 completers (In-person n = 80; Remote n = 35) were analyzed for performance outcomes. Feasibility, adherence, and satisfaction benchmarks were evaluated at baseline, immediately post intervention, and 8 weeks post intervention. Adjusting for baseline performances, outcomes on health literacy and cognitive measures were compared between groups after intervention (at posttest and at 8-week follow-up) using adjusted mean differences (ß coefficients). RESULTS: Eighty in-person and all remote participants completed at least six modules. Both programs had high satisfaction, feasibility, and strong adherence. After adjusting for demographic covariates and baseline values, cognitive and motor cognitive measures between groups were domain specific (e.g., global cognition, executive function, spatial memory, mental tracking capacity, and cognitive integration). DISCUSSION AND IMPLICATIONS: This work explores feasible measures of knowledge acquisition and its link to health literacy and cognitive outcomes. Identifying effective delivery methods may increase involvement in clinical research. Future studies may encourage remote learning for increased accessibility.

Sociodemographic variables associated with risk for diabetic retinopathy.

BACKGROUND: Several systemic and sociodemographic factors have been associated with the development and progression of diabetic retinopathy (DR). However, there is limited investigation of the potential role sociodemographic factors may play in augmenting systemic risk factors of DR. We hypothesize that age, sex, race, ethnicity, income, and insurance payor have an impact on hemoglobin A1c (HbA1c), body mass index, and systolic blood pressure, and therefore an upstream effect on the development of DR and vision-threatening forms of DR (VTDR). METHODS: Multivariable analysis of longitudinal electronic health record data at a large academic retina clinic was performed. Sociodemographic factors included race, ethnicity, income, and insurance payor. Systemic risk factors for DR included hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and body mass index (BMI). VTDR was identified from encounter diagnostic codes indicating proliferative retinopathy or diabetic macular edema. Patient-reported primary address zip codes were used to approximate income level, stratified into quartiles. RESULTS: From 2016 to 2018, 3,470 patients with diabetes totaled 11,437 visits were identified. Black patients had higher HbA1c and SBP compared to White patients. White patients had higher BMI and SBP compared to patients of unknown/other race and greater odds of VTDR than the latter. Patients of Hispanic ethnicity had significantly higher SBP than non-Hispanic patients. Low-income patients had higher BMI and SBP than high-income patients and greater odds of VTDR than the latter. Medicaid recipients had greater odds of VTDR than those with Blue Care Network (BCN) and Blue Cross Blue Shield (BCBS) insurance. Medicaid and Medicare recipients had higher SBP compared to BCBS recipients. Finally, both higher HbA1c and SBP had greater odds of VTDR. There were no differences in odds of VTDR between White and Black patients or between Hispanic and non-Hispanic patients. CONCLUSION: Significant associations exist between certain sociodemographic factors and well-known risk factors for DR. Income and payor were associated with increased severity of systemic risk factors and presence of VTDR. These results warrant further investigation of how risk factor optimization and disease prevention may be further improved by targeted intervention of these modifiable sociodemographic factors.

Randomized Safety and Feasibility Trial of Ultra-Rapid Cooling Anesthesia for Intravitreal Injections.

PURPOSE: To test the safety and preliminary efficacy of rapid, nonpharmacologic anesthesia via cooling for intravitreal injections. DESIGN: Single-center, randomized phase 1 dose-ranging safety study (ClinicalTrials.gov identifier, NCT02872012). PARTICIPANTS: Adults 18 years of age or older with a diagnosis of exudative macular degeneration or diabetic macular edema requiring bilateral anti-vascular endothelial growth factor therapy were included. METHODS: A handheld device was developed to provide anesthesia via cooling to a focal area on the surface of the eye before intravitreal treatment (IVT). In 22 patients undergoing bilateral IVT, 1 eye was randomized to receive standard of care (SOC) lidocaine-based anesthesia and the other eye received cooling-anesthesia at 1 of 5 different temperatures and cooling times. Subjective pain was assessed via the visual analog scale (VAS; range, 1-10) at 2 time points: (1) immediately after IVT and (2) 4 hours after IVT. Treated eyes were assessed for ocular safety 24 hours after IVT. MAIN OUTCOME MEASURES: We determined the occurrence of adverse events in eyes treated with cooling anesthesia. Mean VAS pain scores immediately after IVT and 4 hours after IVT in eyes receiving cooling anesthesia were compared with eyes receiving SOC. RESULTS: A total of 44 eyes were treated, 22 with cooling anesthesia and 22 with SOC. No dose-related toxicity was found with cooling anesthesia. Mild, transient adverse events were recorded in 32% of patients treated with cooling anesthesia versus 44% of patients receiving SOC. The mean±standard error of the mean (SEM) VAS pain scores immediately after intravitreal injection were 2.3 ± 0.4 for patients receiving SOC and 2.2 ± 0.6 in patients receiving -10° C cooling anesthesia (P = 0.8). Mean±SEM pain scores 4 hours after injection were 1.6 ± 0.4 for SOC and 1.2 ± 0.5 in the combined -10° C arms (P = 0.56). Total mean±SEM procedure time was 124 ± 5 seconds for patients treated with cooling anesthesia versus 395 ± 40 seconds for SOC (P < 0.0001). CONCLUSIONS: Ultra-rapid cooling of the eye for anesthesia was well tolerated, with -10° C treatment resulting in comparable levels of anesthesia to SOC with a reduction in procedure time.

Identification of population characteristics through implementation of the Comprehensive Diabetic Retinopathy Program.

BACKGROUND: Diabetic retinopathy is the most common cause of blindness in working-age adults. Characteristics of patients with diabetes presenting to a retina subspecialty clinic have not been adequately studied, limiting our ability to risk stratify patients with diabetic retinopathy. Our goal is to describe an innovative program that collects structured, longitudinal data on patients with diabetes in a retina clinic, and identifies population characteristics to define patient risk stratification. METHODS: Demographics, body-mass index, blood pressure, hemoglobin A1c, smoking history, diabetes type, diabetes duration, kidney disease history, and diagnosis codes were collected on all patients with diabetes at the Kellogg Eye Center retina clinic. A mixed effects negative binomial regression was then performed to assess visit frequency as a function of these variables. Visit frequency was used as a marker for cost of care. A subgroup of patients was surveyed about knowledge of diabetes management goals and barriers to better self-management. RESULTS: There were 2916 patients in the cohort with 1014 in the subgroup. The cohort was predominantly Caucasian (74.5%), with a mean age of 64 years (range 13-99) and a relatively even distribution of sex (53.2% men). The mean maximum hemoglobin A1c was 8.0% (range 4.3-15.7%), and 57.1% had a diagnosis of diabetic retinopathy. Patients averaged 3.9 visits (range 1-27) during the 18-month study period. Blood pressure and duration of diabetes were positively associated with visit frequency (p < 0.0001, p < 0.0001, respectively). Of the surveyed patients, 87.6% knew their goal hemoglobin A1c, while only 45.9% identified the correct blood pressure goal. The most common reported barrier to better self-management was "it's just not working" (47.1%). CONCLUSIONS: Implementation of this program enables the creation of a longitudinal dataset on patients with diabetes. Resulting data can be used to improve quality of care provided to patients at a retina clinic. The findings suggest considerable healthcare resources are being directed to a small patient population. This enhanced understanding of characteristics of patients with diabetes will improve efforts to preserve vision and utilize health system resources efficiently.

Shedding light on a potential hazard: Dental light-curing units.

BACKGROUND: Dental light-curing units (LCUs) are powerful sources of blue light that can cause soft-tissue burns and ocular damage. Although most ophthalmic research on the hazards of blue light pertains to low levels from personal electronic devices, computer monitors, and light-emitting diode light sources, the amount of blue light emitted from dental LCUs is much greater and may pose a "blue light hazard." METHODS: The authors explain the potential risks of using dental LCUs, identify the agencies that provide guidelines designed to protect all workers from excessive exposure to blue light, discuss the selection of appropriate eye protection, and provide clinical tips to ensure eye safety when using LCUs. RESULTS: While current literature and regulatory standards regarding the safety of blue light is primarily based on animal studies, sufficient evidence exists to suggest that appropriate precautions should be taken when using dental curing lights. The authors found it difficult to find on the U.S. Food and Drug Administration database which curing lights had been cleared for use in the United States or Europe and could find no database that listed which brands of eyewear designed to protect against the blue light has been cleared for use. The authors conclude that more research is needed on the cumulative exposure to blue light in humans. Manufacturers of curing lights, government and regulatory agencies, employers, and dental personnel should collaborate to determine ocular risks from blue light exist in the dental setting, and recommend appropriate eye protection. Guidance on selection and proper use of eye protection should be readily accessible. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The Centers for Disease Control and Prevention Guidelines for Infection Control in the Dental Health-Care Setting-2003 and the Occupational Safety and Health Administration Bloodborne Pathogen Standard do not include safety recommendations or regulations that are directly related to blue light exposure. However, there are additional Occupational Safety and Health Administration regulations that require employers to protect their employees from potentially injurious light radiation. Unfortunately, it is not readily evident that these regulations apply to the excessive exposure to blue light. Consequently employers and dental personnel may be unaware that these Occupational Safety and Health Administration regulations exist.

Blood Pressure Is Associated with Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Treatment in Patients with Diabetes.

PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF) injections are used commonly in the treatment of diabetic retinopathy (DR), but the need for treatment and frequency of administration vary considerably among patients. There is no way to predict which patients will require treatment and how frequently injections will be needed. This study aimed to identify factors associated with receiving anti-VEGF injections and the number of treatments received in an 18-month period in patients with diabetes. DESIGN: Retrospective cohort study. PARTICIPANTS: Two thousand nine hundred sixteen patients with diabetes treated at the Kellogg Eye Center Retina Clinic from June 1, 2016, through December 31, 2017. METHODS: Retrospective analysis was performed with institutional review board approval using data collected from diabetic patients treated at the retina clinic at the Kellogg Eye Center. Logistic regression was used to identify demographic and medical factors associated with receiving at least 1 injection. Negative binomial regression was used to model the number of anti-VEGF injections. MAIN OUTCOME MEASURES: Receiving at least 1 anti-VEGF injection and the number of anti-VEGF injections received during the study period. RESULTS: Systolic blood pressure and a diagnosis of DR were associated significantly with receiving an injection. A history of kidney disease was associated positively with the number of injections received. Type 1 diabetes was associated negatively with receiving an injection and the number of injections. Current hemoglobin A1c level was not associated with either receiving an injection or the number of injections. CONCLUSIONS: Elevated blood pressure is associated significantly with the need for treatment with anti-VEGF injections in patients with diabetes, and a diagnosis of type 1 diabetes is associated negatively with both receiving treatment and the number of injections. Of note, current glycemic control is not associated significantly with either outcome measure. To our knowledge, these associations have not been previously reported, and imply that factors that confer risk for DR development may not be the same that confer risk for treatment.

Diabetic retinopathy: research to clinical practice.

BACKGROUND: Diabetic Retinopathy (DR) is a leading cause of visual impairment in the United States. The CDC estimates that the prevalence of DR will triple from 2005 to 2050. MAIN BODY: The report summarizes major past advances in diabetes research and their impact on clinical practice. Current paradigms and future directions are also discussed. CONCLUSIONS: DR is a leading cause of visual impairment in the US. Significant progress has been made in the understanding and treatment of DR, but rising prevalence demands innovative approaches to management in the future.

Predictors of Response to Intravitreal Anti-Vascular Endothelial Growth Factor Treatment of Age-Related Macular Degeneration.

PURPOSE: To identify factors that influence visual and anatomic response to treatment with intravitreal anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (AMD). DESIGN: Observational cohort study. METHODS: Seventy-two patients were included in this study. Best-corrected Snellen visual acuity (VA) and central foveal thickness measured on optical coherence tomography (OCT) at time of treatment and post-treatment follow-up visits were recorded. Associations between demographic, behavioral, and genetic risk factors and the 2 outcomes were analyzed using mixed-effects linear regression models. Two loci in complement factor H (CFH) were included in a risk score to determine the association between CFH risk and improvement in VA and central foveal thickness. RESULTS: There was a small improvement in VA following anti-VEGF treatment (mean: 3.7 ± 3.0 letters), which was not statistically significant. Significant improvement in VA was observed for the nonrisk CFH Y402H genotype (P < .001) and for a low CFH risk score (P = .019). Regarding the outcome of change in central foveal thickness, improvement was noted in all genotype groups, but reduction after treatment was significantly higher in the low CFH risk score group (P = .033). A significant improvement in mean VA was seen among smokers (P < .001), but this relationship was not observed for central foveal thickness. CONCLUSION: After anti-VEGF therapy, significant improvement in VA was observed for low-risk CFH genotypes and subjects with a low risk score. There was a statistically significant reduction in central foveal thickness overall, and subjects with a low CFH risk score improved more than the high-risk group.