Systemic medications for sickle cell disease and potential applications for sickle cell retinopathy.

PURPOSE OF REVIEW: To review the literature evaluating systemic medications for treatment of sickle cell disease (SCD) and their applications for sickle cell retinopathy. RECENT FINDINGS: Prior studies have demonstrated the efficacy of traditional systemic therapies in reducing the risk of development of sickle cell retinopathy. Since 2017, several new and promising disease-modifying therapies for sickle cell disease have been approved for clinical use, including the first genetic therapies such as exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel). These treatments have shown promising results for systemic management but are not widely utilized due to limited access and high cost. The efficacy of these therapies for the prevention of sickle cell retinopathy remains unknown and opens the door to new avenues for research. Furthermore, the role of systemic therapy for the management of hemoglobin SC (HbSC) disease, which has milder systemic effects but higher likelihood of causing retinopathy, remains poorly understood. SUMMARY: Hydroxyurea has been a mainstay of systemic management of SCD with prior work suggesting its ability to reduce the likelihood of developing retinopathy. There are several new and potentially curative systemic therapies for SCD, though their role in retinopathy prevention and management has not been studied extensively. Future studies are necessary to understand the implications of these emerging therapies for sickle cell retinopathy.

EVALUATION OF MACULAR FLOW VOIDS ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AS POTENTIAL BIOMARKERS FOR SILENT CEREBRAL INFARCTION IN SICKLE CELL DISEASE.

PURPOSE: To determine the relationship between macular microvascular abnormalities on optical coherence tomography angiography and silent cerebral infarctions (SCIs) on cerebral magnetic resonance imaging in sickle cell disease. METHODS: Patients (age <18 years old) from our previous pediatric sickle cell disease study cohort who had prior optical coherence tomography angiography and brain magnetic resonance imaging were identified. Brain magnetic resonance imaging images were compared with macular optical coherence tomography angiography scans to identify macular vascular density differences between patients with SCI and without SCI. RESULTS: Sixty-eight eyes from 34 patients who underwent optical coherence tomography angiography were evaluated, of whom 28 eyes from 14 patients met the inclusion criteria for this study. Eight patients (57%) with SCI and 6 patients (43%) without SCI were identified. The mean age (17 years in SCI and 16.3 years in non-SCI) was comparable between groups. There was no statistically significant difference in systemic complications. Deep capillary plexus vessel density was lower in the temporal quadrant in patients with SCI (49.3% vs. 53.7%, P = 0.014). CONCLUSION: Patients with SCI were found to have lower vessel density in the deep capillary plexus compared with those without SCI. This finding suggests that deep capillary plexus vessel density may have utility as an imaging biomarker to predict the presence of SCI.

Symptom-Based Risk Factors for Retinal Tears and Detachments in Suspected Posterior Vitreous Detachment.

INTRODUCTION: The aim of this study was to determine symptom-level risk factors for retinal tear/retinal detachment (RT/RD) in our patients presenting with symptoms of posterior vitreous detachment (PVD). METHODS: We conducted a prospective cohort study of patients presenting to outpatient ophthalmology clinics at a single academic institution with complaint(s) of flashes, floaters, and/or subjective field loss (SFL). Patients received a standardized questionnaire regarding past ocular history and symptom characteristics including number, duration, and timing of flashes and floaters, prior to dilated ocular examination. Final diagnosis was categorized as RT/RD, PVD, ocular migraine, vitreous syneresis, or "other." Simple and multivariate logistic regressions were used to identify symptoms predictive of various pathologies. RESULTS: We recruited 237 patients (age 20-93 years) from March 2018 to March 2019. The most common diagnosis was PVD (141, 59.5%), followed by vitreous syneresis (38, 16.0%) and RT/RD (34, 14.3%). Of those with RT/RD, 16 (47.1%) had retinal tear and 15 (44.1%) had RD. Significant differences in demographic and examination-based factors were observed between these groups. Symptom-based predictive factors for RT/RD were the presence of subjective visual reduction (SVR; OR 2.77, p = 0.03) or SFL (OR 2.47, p = 0.04), and the absence of either floaters (OR 4.26, p = 0.04) or flashes (OR 2.95, p = 0.009). The number, duration, and timing of flashes and floaters did not predict the presence of RT/RD in our cohort. Within the RT/RD group, patients with RT were more likely to report floaters (100% vs. 66.7%, p = 0.018) and less likely to report SFL (0% vs. 86.7%, p < 0.001) compared to those with RD. CONCLUSION: While well-known demographic and exam-based risk factors for RT/RD exist in patients with PVD symptoms, the relative importance of symptom characteristics is less clear. We found that the presence of SVR and SFL, as well as the absence of either flashes or floaters, predicts RT/RD in patients with PVD symptoms. However, the number, duration, and timing of flashes and floaters may be less relevant in the triage of these patients.

UTILITY OF ULTRA-WIDEFIELD RETINAL IMAGING FOR THE STAGING AND MANAGEMENT OF SICKLE CELL RETINOPATHY.

PURPOSE: To determine whether ultra-widefield (UWF) retinal imaging changes the staging or management of sickle cell retinopathy compared with clinical examination. METHODS: Prospective, observational study including patients with sickle cell disease. All patients underwent dilated fundus examination by a fellowship-trained retina specialist, as well as UWF fundus photography (FF) and fluorescein angiography (FA). Sickle retinopathy stage and treatment recommendation per eye were determined after clinical examination, UWF-FF, and UWF-FA, respectively, and differences in retinopathy stage and treatment recommendation were compared. RESULTS: A total of 70 eyes from 35 patients (17 women, 48.6%), mean age 30.4 years, were included. Sickle genotypes included 26 patients with sickle SS (74.3%), 7 SC (20.0%), and 2 ß(+)thalassemia (5.7%). Based on examination, most eyes (42/70; 60.0%) had no visible retinopathy. Based on UWF-FF, about half of the eyes were found to be Goldberg Stage 2 or above (36/70; 51.4%). Based on UWF-FA, nearly all eyes were Goldberg Stage 2 or above (63/70; 90%). However, clinical examination reliably detected neovascularization, and in no case did the addition of UWF imaging change management relative to examination alone. CONCLUSION: Ultra-widefield imaging detects a higher stage of sickle cell retinopathy compared with clinical examination alone, but these differences may not be clinically significant.

Visual function quality of life measure changes upon conversion to neovascular age-related macular degeneration in second eyes.

PURPOSE: To determine changes in quality of life measures when choroidal neovascularization (CNV) developed in the second eye of patients with initially unilateral neovascular age-related macular degeneration (AMD). METHODS: We analyzed responses to the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ), 36-item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS) at baseline, and prior to and following second eye CNV diagnosis in 92 participants enrolled in two Submacular Surgery Trials. Paired t-tests for sample sizes over 30 and Wilcoxon signed-rank tests for sample sizes <30 were performed to compare scores. RESULTS: CNV development resulted in statistically and clinically significant changes in responses to 20 of 39 NEI-VFQ items, indicating visual function decline during a mean interval of 25 months. Little difference was noted between baseline scores and prior to CNV diagnosis, which averaged 8.9 months duration. Subscales demonstrated a statistically significant decline in general vision, near activities, distance activities, social functioning, role difficulties, dependency, and driving. There were minimal changes in the HADS and SF-36 scales. CONCLUSION: CNV development in the second eye had a dramatic effect on visual functioning based on patient responses to the NEI-VFQ questionnaire. Our investigation is believed to be the first study using data collected prospectively to demonstrate vision-related quality of life changes that resulted from development of CNV in AMD patients.

Changes in Retinal Nonperfusion Associated with Suppression of Vascular Endothelial Growth Factor in Retinal Vein Occlusion.

PURPOSE: To assess changes in retinal nonperfusion (RNP) in patients with retinal vein occlusion (RVO) treated with ranibizumab. DESIGN: Secondary outcome measure in randomized double-masked controlled clinical trial. PARTICIPANTS: Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO). METHODS: Subjects were randomized to 0.5 or 2.0 mg ranibizumab every month for 6 months and then were re-randomized to pro re nata (PRN) groups receiving either ranibizumab plus scatter laser photocoagulation or ranibizumab alone for an additional 30 months. MAIN OUTCOME MEASURES: Comparison of percentage of patients with increased or decreased area of RNP in patients with RVO treated with 0.5 versus 2.0 mg ranibizumab, during monthly injections versus ranibizumab PRN, and in patients treated with ranibizumab PRN versus ranibizumab PRN plus laser. RESULTS: In RVO patients given monthly injections of 0.5 or 2.0 mg ranibizumab for 6 months, there was no significant difference in the percentage who showed reduction or increase in the area of RNP. However, regardless of dose, during the 6-month period of monthly injections, a higher percentage of patients showed a reduction in area of RNP and a lower percentage showed an increase in area of RNP compared with subsequent periods of ranibizumab PRN treatment. After the 6-month period of monthly injections, BRVO patients, but not CRVO patients, randomized to ranibizumab PRN plus laser showed significantly less progression of RNP compared with patients treated with ranibizumab PRN. CONCLUSIONS: Regardless of dose (0.5 or 2.0 mg), monthly ranibizumab injections promote improvement and reduce progression of RNP compared with PRN injections. The addition of scatter photocoagulation to ranibizumab PRN may reduce progression of RNP in patients with BRVO, but a statistically significant reduction was not seen in patients with CRVO.

CORRELATION OF MULTIMODAL IMAGING IN SICKLE CELL RETINOPATHY.

PURPOSE: To correlate macular findings on spectral domain optical coherence tomography (SDOCT) and optical coherence tomography angiography (OCTA) with quantitative ischemic index calculations on ultra-wide-field fluorescein angiography (UWFFA) in patients with sickle cell retinopathy. METHODS: In this retrospective case series, SDOCT, OCTA, and UWFFA images of patients with sickle cell retinopathy were evaluated. Eyes were staged based on the Goldberg classification of proliferative sickle cell retinopathy. Focal areas of macular thinning were assessed on SDOCT, macular vessel density was derived from OCTA, and peripheral ischemic index was calculated from UWFFA. RESULTS: Eighteen eyes of 10 patients were included. Mean age was 36.8 ± 16.8 years, and 6 patients (11 eyes) were SS, 3 patients (5 eyes) were SC, and 1 patient (2 eyes) was Sß thalassemia in hemoglobin electrophoresis. Abnormal macular findings included inner retinal atrophy in 11 eyes (61%) on SDOCT, vascular remodeling and nonperfusion in the superficial and deep retinal capillary plexus in 12 eyes (67%) on OCTA, and macular microvascular abnormalities in 9 eyes (50%) on UWFFA. Sickle cell retinopathy Stage I was identified in 4 eyes (22.2%), Stage II in 8 eyes (44.4%), and Stage III in 6 eyes (33.3%). Mean ischemic index was 14.1 ± 9.1%. Ischemic index was significantly correlated with hemoglobinopathy subtype (23.7 ± 9.8%, 9.3 ± 5.4%, and 16.3 ± 3.2%, for SC, SS, and Sß thalassemia disease, respectively), stage of sickle cell retinopathy (22.5 ± 9.2%, 12.5 ± 4.9%, and 4.5 ± 0.73% for Stages III, II, and I, respectively), and presence of retinal thinning on SDOCT (17.4 ± 9.7% vs. 8.8 ± 5.1%, respectively). CONCLUSION: Multimodal imaging can provide a more complete description of the microvascular and structural alterations associated with sickle retinopathy. The correlation between the severity of peripheral nonperfusion and stage and subtype of retinopathy suggests that UWF imaging may be a useful tool in the evaluation of these patients.

Ophthalmic Manifestations of Sickle Cell Disease.

Sickle cell disease (SCD), the most common inherited blood disorder, is characterized by defective oxygen transport. Every part of the eye can be affected by microvascular occlusions from SCD; however, the major cause of vision loss is proliferative sickle cell retinopathy (PSR). Although individuals with the HbSS genotype of SCD manifest more systemic morbidity and those with the HbSC genotype have a milder clinical course, those with HbSC have an increased risk of developing PSR and resultant vision loss. Sickle cell retinopathy has a variable phenotype, even among individuals with the same genotype. Most patients with SCD maintain good vision because the associated retinopathy occurs in the retinal periphery, and any associated "sea fan" neovascularization has a high tendency to autoinfarct and regress. Vision loss from PSR is largely preventable via regular retinal examinations and treatment as indicated. Novel retinal imaging techniques such as wide-field fluorescein angiography, spectral domain optical coherence tomography, and optical coherence tomography angiography can identify evidence of retinal microvascular occlusions in most patients with SCD. Further study is necessary to discover which individuals are at highest risk for vision loss, which of these retinal imaging modalities is clinically important, and which systemic treatments may decrease risk of vision loss from sickle cell retinopathy.

Scatter Photocoagulation Does Not Reduce Macular Edema or Treatment Burden in Patients with Retinal Vein Occlusion: The RELATE Trial.

PURPOSE: To determine whether scatter and grid laser photocoagulation (laser) adds benefit to ranibizumab injections in patients with macular edema from retinal vein occlusion (RVO) and to compare 0.5-mg with 2.0-mg ranibizumab. DESIGN: Randomized, double-masked, controlled clinical trial. PARTICIPANTS: Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO). METHODS: Subjects were randomized to 0.5 mg or 2.0 mg ranibizumab every 4 weeks for 24 weeks and re-randomized to pro re nata ranibizumab plus laser or ranibizumab alone. MAIN OUTCOME MEASURES: Mean change from baseline best-corrected visual acuity (BCVA) at week 24 for BCVA at weeks 48, 96, and 144 for second randomization. RESULTS: Mean improvement from baseline BCVA at week 24 was 15.5 and 15.8 letters in the 0.5-mg and 2.0-mg CRVO groups, and 12.1 and 14.6 letters in the 0.5-mg and 2.0-mg BRVO groups. For CRVO, but not BRVO, there was significantly greater reduction from baseline mean central subfield thickness (CST) in the 2.0-mg versus 0.5-mg group (396.1 vs. 253.5 µm; P = 0.03). For the second randomization in CRVO patients, there was no significant difference from week 24 BCVA in the ranibizumab plus laser versus the ranibizumab only groups at week 48 (-3.3 vs. 0.0 letters), week 96 (+0.69 vs. -1.6 letters), or week 144 (+0.4 vs. -6.7 letters), and a significant increase from week 24 mean CST at week 48 (+94.7 vs. +15.2 µm; P = 0.05) but not weeks 96 or 144. For BRVO, there was a significant reduction from week 24 mean BCVA in ranibizumab plus laser versus ranibizumab at week 48 (-7.5 vs. +2.8; P < 0.01) and week 96 (-2.0 vs. +4.8; P < 0.03), but not week 144, and there were no differences in mean CST change from week 24 at weeks 48, 96, or 144. Laser failed to increase edema resolution or to reduce the ranibizumab injections between weeks 24 and 144. CONCLUSIONS: In patients with macular edema resulting from RVO, there was no short-term clinically significant benefit from monthly injections of 2.0-mg versus 0.5-mg ranibizumab injections and no long-term benefit in BCVA, resolution of edema, or number of ranibizumab injections obtained by addition of laser treatment to ranibizumab.

Terminology for Retinal Findings in Sickle Cell Disease Research: A Scoping Review.

OBJECTIVE: To review the current sickle cell disease (SCD) literature to assess how "retinopathy" has been defined and to identify ocular outcomes that have been measured and described. DESIGN: A systematic scoping review of SCD literature was completed regarding ocular manifestations of SCD and vision outcomes across all medical specialties. SUBJECTS: Participants with SCD and control patients were included in our data extraction. METHODS: We reviewed English-language literature from 2000 to 2021 for eligible studies by searching PubMed, Google Scholar, Embase, and the Cochrane library using terms to encompass SCD and ocular findings. MAIN OUTCOME MEASURES: Data collection included study information, patient characteristics, vision-related findings (inclusion criteria and/or study outcomes), and retinopathy characteristics (definition, when, how and by whom diagnosed). RESULTS: We identified 4006 unique citations and 111 were included in the analysis. Ophthalmologists were senior authors of about half (59/111; 53.2%) of the articles; most articles were published between 2016 and 2021 (71/111; 70.0%). The studies had been conducted primarily in North America (54/111; 48.6%) or Europe (23/111; 20.7%); designs were cross-sectional (51/111; 45.9%), prospective cohort (28/111; 25.2%), retrospective cohort (27/111; 24.3%), and case-control (4/111; 3.6%). Among studies reporting any retinopathy, it was commonly defined as a combination of nonproliferative sickle cell retinopathy and proliferative sickle cell retinopathy (PSR; 52/87; 59.8%), infrequently as PSR only (6/87; 6.9%), or not defined at all (23/87; 26.4%). The Goldberg classification was used to grade retinopathy in almost half of the studies (41/87; 47.1%). Investigators reporting diagnostic methods used clinical fundus examination (56/111; 50.4%), OCT (24/111; 21.6%), fluorescein angiography (20/111; 18.0%), ultrawidefield fundus photographs (15/111; 13.5%), and OCT angiography (10/111; 9.0%), or did not report methods (28/111; 25.2%). CONCLUSIONS: There are inconsistencies in documentation of methods and outcomes in studies of SCD ophthalmic findings. Particularly concerning is the lack of documentation of ophthalmic examination methods, qualifications of examiners, and clarity and specificity of sickle cell retinopathy definitions. With the increase in SCD treatment research and novel systemic therapies available, it is important to adopt clear and consistent descriptions and rigorous data collection and reporting of ophthalmic outcomes in SCD studies. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Effect of Race and Insurance Status on Treatment and Outcomes in Diabetic Retinopathy: Analysis of 43 274 Eyes Using the IRIS Registry.

Purpose: To examine disparities in visual acuity (VA) outcomes 1 year and 2 years after initiation of diabetic retinopathy (DR) or diabetic macular edema (DME) treatment in patients based on race/ethnicity and insurance status, accounting for disease severity. Methods: This retrospective analysis used the IRIS Registry and included DR patients older than 18 years with documented antivascular endothelial growth factor (anti-VEGF) treatment and VA data for at least 2 years. International Classification of Diseases, Tenth Revision, Clinical Modification codes were used to determine the severity of DR and DME presence. VA outcomes were assessed using multivariable linear regressions and anti-VEGF drug use by multivariable logistic regressions, with race and insurance status as independent variables. Main outcome measures comprised the mean VA change at 1 year and 2 years and percentage of patients treated with bevacizumab. Results: The study included 43 274 eyes. White patients presented with a higher mean VA and lower mean DR severity than Black patients and Hispanic patients. Multivariable logistic regression showed Hispanic patients were significantly more likely to be treated with bevacizumab than White patients across all insurance types, controlling for disease severity and VA. After 1 year, the letter improvement was 1.73, 1.33, and 1.13 in White patients, Black patients, and Hispanic patients, respectively. Multivariable linear regression suggested that across races, Medicaid-insured patients had significantly smaller gains in VA than privately insured patients. Conclusions: Race-based and insurance-based differences in 1-year and 2-year outcomes after anti-VEGF treatment for DR and anti-VEGF treatment patterns suggest a need to ensure earlier and more effective treatment of minority and underserved patients in the United States.

Retinal characteristics in eyes with pathologic myopia among individuals self-identifying as Black.

OBJECTIVE: Investigate retinal characteristics of pathologic myopia (PM) among patients self-identifying as Black. DESIGN: Retrospective cohort single-institution retrospective medical record review. METHODS: Adult patients between January 2005 and December 2014 with International Classification of Diseases (ICD) codes consistent with PM and given 5-year follow-up were evaluated. The Study Group consisted of patients self-identifying as Black, and the Comparison Group consisted of those not self-identifying as Black. Ocular features at study baseline and 5-year follow-up visit were evaluated. RESULTS: Among 428 patients with PM, 60 (14%) self-identified as Black and 18 (30%) had baseline and 5-year follow-up visits. Of the remaining 368 patients, 63 were in the Comparison Group. For the study (n = 18) and Comparison Group (n = 29), median (25th percentile, 75th percentile) baseline visual acuity was 20/40 (20/25, 20/50) and 20/32 (20/25, 20/50) in the better-seeing eye and 20/70 (20/50, 20/1400) and 20/100 (20/50, 20/200), respectively, in the worse-seeing eye. In the eyes that did not have choroidal neovascularization (CNV) in the study and Comparison Group, median study baseline optical coherence tomography central subfield thickness was 196 µm (169, 306 µm) and 225 µm (191, 280 µm), respectively, in the better-seeing eye and 208 µm (181, 260 µm) and 194 µm (171, 248 µm), respectively, in the worse-seeing eye. Baseline prevalence of CNV was 1 Study Group eye (3%) and 20 Comparison Group eyes (34%). By the 5-year visit, zero (0%) and 4 (15%) additional eyes had CNV in the study and Comparison Group, respectively. CONCLUSION: These findings suggest that the prevalence and incidence of CNV may be lower in patients with PM self-identifying as Black when compared with individuals of other races.

Severe Intraocular Inflammation Following Intravitreal Faricimab.

Importance: Monitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences in clinical trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance potential benefits and risks of these agents. Objective: To provide descriptions of 3 initially culture-negative cases of acute, severe, posterior-segment IOI events occurring within the same month following intravitreal faricimab injections at a single institution. Design, Setting, and Participants: In this case series, 3 patients manifesting acute, severe IOI following intravitreal injection of faricimab were identified between September 20, 2023, and October 20, 2023. Exposure: Faricimab, 6 mg (0.05 mL of 120 mg/mL solution), for neovascular age-related macular degeneration among patients previously treated with aflibercept; 1 patient also had prior exposure to bevacizumab. Main Outcomes and Measures: Visual acuity, vitreous taps for bacterial or fungal cultures, and retinal imaging. Results: All 3 patients received intravitreal faricimab injections between September 20 and October 20, 2023, from 2 different lot numbers (expiration dates, July 2025) at 3 locations of 1 institution among 3 of 19 retina physicians. Visual acuities with correction were 20/63 OS for patient 1, 20/40 OD for patient 2, and 20/20 OS for patient 3 prior to injection. All 3 patients developed acute, severe inflammation involving the anterior and posterior segment within 3 to 4 days after injection, with visual acuities of hand motion OS, counting fingers OD, and hand motion OS, respectively. Two patients were continuing faricimab treatment while 1 patient was initiating faricimab treatment. All received intravitreal ceftazidime, 2.2 mg/0.1 mL, and vancomycin, 1 mg/0.1 mL, immediately following vitreous taps. All vitreous tap culture results were negative. One patient underwent vitrectomy 1 day following presentation. Intraoperative vitreous culture grew 1 colony of Staphylococcus epidermidis, judged a likely contaminant by infectious disease specialists. All symptoms resolved within 1 month; visual acuities with correction were 20/100 OS for patient 1, 20/50 OD for patient 2, and 20/30 OS for patient 3. Conclusions and Relevance: In this case series, 3 patients with acute, severe IOI within 1 month at 3 different locations among 3 ophthalmologists of 1 institution following intravitreal faricimab could represent some unknown storage or handling problem. However, this cluster suggests such inflammatory events may be more common than anticipated from faricimab trial reports, emphasizing the continued need for vigilance to detect and report such cases following regulatory approval.

Long-term follow-up of vascular endothelial growth factor inhibitor therapy for neovascular age-related macular degeneration.

PURPOSE OF REVIEW: To discuss the most recent literature regarding the long-term use (≥52 weeks of follow-up) of antivascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (NVAMD). RECENT FINDINGS: Intravitreal ranibizumab has been demonstrated to provide outstanding vision outcomes relative to the standard therapy in patients with NVAMD. The VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD studies showed that patients managed with intravitreal aflibercept achieved visual acuity and anatomic improvements similar to individuals managed with monthly ranibizumab while receiving an average of five fewer injections during the first 12 months of treatment. In the Comparison of AMD Treatment Trials, intravitreal bevacizumab dosed monthly met noninferiority to ranibizumab monthly, as well as noninferiority to ranibizumab dosed as-needed with respect to change in visual acuity 1 year after the treatment initiation. Furthermore, patients switched to as-needed regimens in their second year of follow-up from monthly dosing during the first year demonstrated an incremental loss of visual acuity during the second year of follow-up irrespective of the drug used. To date, trials evaluating anti-VEGF therapy for NVAMD demonstrate a low incidence of serious ocular or systemic adverse events. However, the potential for deleterious effects of long-term (beyond 2 years) pan-VEGF blockade remains unknown. SUMMARY: Patients with NVAMD enjoy heretofore unprecedented vision gains when managed with anti-VEGF therapy, and the limited body of evidence to date regarding long-term anti-VEGF treatment shows these vision gains can be maintained through 2 years. Further investigation is needed to explore the effects of long-term anti-VEGF therapy beyond 2 years.

Trends in Retinopathy of Prematurity Care in the United States 2009-2018: A Nationwide Analysis Using National Inpatient Sample.

PURPOSE: Retinopathy of prematurity (ROP) represents a leading cause of childhood blindness. The purpose of our study was to evaluate incidence, trends in cost and length of hospital stay, and risk factors for ROP using a publicly available population-based dataset, the National Inpatient Sample. DESIGN: This cross-sectional study analyzed data from 2009 to 2018 using the National Inpatient Sample. PARTICIPANTS: Premature neonates (n = 717 277) who met the screening criteria for ROP with gestational age of ≤ 30 weeks or birthweight (BW) of ≤ 1500 g were identified. METHODS: Database analysis. MAIN OUTCOME MEASURES: Incidence, demographics, risk factors for ROP development, trends in cost, and length of stay were evaluated. RESULTS: In total, incidence of ROP increased from 11% in 2009 to 15% in 2018 (P < 0.001). Multivariate logistic regression model of ROP development showed its associations with female sex (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.10-1.17), Hispanic (OR, 1.10; 95% CI, 1.03-1.18), and Black (OR, 0.91; 95% CI 0.86-0.96) ethnicity. Neonates with lower BWs, particularly those in the 500- to 999-g subgroup (OR, 2.64; 95% CI, 2.44-2.85) and younger gestational ages, particularly those born between 25 and 28 weeks gestational age (OR, 2.41; 95% CI, 2.25-2.58), had increased risk of developing ROP. Comorbidities associated with the development of ROP were perinatal jaundice (OR, 1.84; 95% CI, 1.74-1.94), patent ducts arteriosus (OR, 1.67; 95% CI, 1.60-1.75), intraventricular hemorrhage (OR, 1.41; 95% CI, 1.35-1.48), perinatal infection (OR, 1.84; 95% CI, 1.74-1.94), and respiratory distress syndrome (OR, 1.05; 95% CI, 1.01-1.10). CONCLUSIONS: Retinopathy of prematurity develops in about 1 of 10 premature infants and incidence has been shown to be increasing. Significant risk factors were female sex, Hispanic ethnicity, lower BW, younger gestational age, and systemic comorbidities, including perinatal jaundice, patent ductus arteriosus, intraventricular hemorrhage, perinatal sepsis, and respiratory distress syndrome. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

National emergency department trends for endogenous endophthalmitis: an increasing public health challenge.

BACKGROUND/OBJECTIVE: To characterize incidence rates and identify risk factors for admission and mortality in patients with endogenous endophthalmitis (EE) in the United States (US). SUBJECTS/METHODS: Patients with EE were identified using the Nationwide Emergency Department (NEDS) Database from 2006 to 2017 in this cross-sectional study. Subjects were required to have diagnoses of both endophthalmitis and septicaemia using contemporary International Classification of Diseases diagnosis codes. Incidence rates, mortality rates and demographics were evaluated. Risk factors for admission and mortality were identified using weighted logistic regression analysis. RESULTS: A total of 6400 patients with EE were identified. Incidence increased from 0.10 (95% confidence interval [CI]: 0.07-0.12) per 100,000 in the US population in 2006 to 0.25 (95% CI: 0.21-0.30) in 2017 (p < 0.05). Most were female (55.4%), insured with Medicare (53.5%), were in the first income quartile earnings (29.3%) [bottom 25% income bracket], lived in the South (40.5%), and presented to metropolitan teaching hospitals (66.6%). Mortality increased from 8.6% (95% CI: 3.8-18.3%) in 2006 to 13.8% (95% CI: 9.7-19.2%) in 2017 (p = 0.94). Factors predicting admission included older age (odds ratio [OR] 32.59; [95% CI 2.95-359.78]) and intravenous drug use (OR 14.90 [95% CI: 1.67-133.16]). Factors associated with increased mortality included: human immunodeficiency virus infection/immune deficiencies (OR 2.58 [95% CI: 1.26-5.28]), heart failure (OR 2.12 [95% CI: 1.47-3.05]), and hepatic infections/cirrhosis (OR 1.89 [95% CI: 1.28-2.79]). Pneumonia and renal/urinary tract infections (UTI) were associated with both increased hospital admission [(pneumonia OR 9.64 (95% CI: 1.25-74.35, p = 0.030), renal/UTI OR 4.09 (95% CI: 1.77-9.48)] and mortality [(pneumonia OR 1.64 (95% CI: 1.17-2.29, p = 0.030), renal/UTI OR 1.87 (95% CI: 1.18-2.97)]. Patients with diabetes mellitus (DM) had decreased odds ratio for mortality (OR 0.49 [95% CI: 0.33-0.73]). CONCLUSION: EE has increased in incidence throughout US. The two systemic factors that conferred both an increase in mortality and admission were pneumonia, and renal/UTI. Additional exploration of the potential protective association of DM with decreased mortality in this context is needed.

Disparities in Eye Care Utilization by Self-Reported Vision Difficulty and Diabetes Status in the United States.

PURPOSE: To assess differences in eye care utilization by vision difficulty (VD), diabetes status, and sociodemographic characteristics for American adults. METHODS: The analysis pooled cross-sectional data from the National Health Interview Survey (2010-2018) from US adults ≥ 18 years. The outcome measure was eye care utilization in the past year. The primary independent variable included four groups: no VD or diabetes, only diabetes, only VD, and diabetes and VD. VD was defined as self-reported difficulty seeing even with glasses or contacts. Diabetic status was defined as ever receiving this diagnosis by a health professional. Multivariable logistic regression analyses examined associations between eye care utilization, VD, diabetic status, and sociodemographic characteristics. RESULTS: Of the 284,599 adults included in this study, the majority were female (55%), White (73%), and non-Hispanic (84%). In regression analysis, as compared to adults without diabetes or VD, adults with both diabetes and VD had the greatest utilization (OR = 2.49, 99% CI = 2.18-2.85). Females had higher utilization than men (OR = 1.45, 99% CI = 1.41-1.50). Higher levels of education was associated with greater utilization (OR = 1.82, 99% CI = 1.72-1.92). White and American Indian adults without diabetes had higher utilization compared to other races (OR = 1.17, 99% CI = 1.12-1.24, 0.98-1.39). CONCLUSION: While adults with VD and diabetes are better connected to eye care, significant eye care disparities persist for marginalized groups in the U.S. Identifying and understanding these disparities and eliminating barriers to care is critical to better support all patient populations.

Self-Reported Vision Impairment and Food Insecurity in the US: National Health Interview Survey, 2011-2018.

PURPOSE: To determine if vision impairment (VI) is associated with food insecurity among the United States (US) adults. METHODS: This is a cross-sectional study of US adults ≥18 years below a threshold of 150% poverty from the National Health Interview Survey (NHIS), years 2011-2018. Outcome measures included food insecurity status, based on response to the NHIS adult (10-item) food insecurity tool, either as a binary (food secure or insecure) or ordinal (high, marginal, low, and very low) variable. VI was defined as self-reported trouble seeing, even when wearing glasses or contact lenses. Multivariable logistic regression analyses adjusted for potential confounders examined associations between VI and food insecurity. RESULTS: Participants (N = 62075) were majority female (57%), White (62%), and non-Hispanic (74%). Of them, 16% reported VI and 28% were food insecure. In fully adjusted logistic regression models, adults with VI had 216% higher odds (95% CI = 2.01-2.31) of being food insecure than adults without VI. Further, there was a dose-response relationship between VI and food insecurity noted in a multinomial model: VI predicted 159% higher risk of marginal food security (95% CI = 1.44-1.75), 197% higher risk of low food security (95% CI = 1.80-2.16), and 295% higher risk of very low food security (95% CI = 2.69-3.22), as compared to high food security. CONCLUSION: VI is associated with food insecurity, increasingly so among adults with highest levels of food insecurity in this national sample of low-income US adults. This data highlights the need for targeted interventions to address and reduce the burden of food insecurity among US adults with VI.