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The goal of a diagnostic test is to provide information on the probability of disease. In this article, we review the principles of diagnostic test characteristics, including sensitivity, specificity, positive and negative predictive value, receiver operating characteristics curves, likelihood ratios, and interval likelihood ratios. We illustrate how interval likelihood ratios optimize the information that can be obtained from test results that can take on >2 values, how they are reflected in the slope of the receiver operating characteristics curve, and how they can be easily calculated from published data.

Objective: To characterize and predict limited early responders (LER) in eyes with retinal vein occlusion (RVO) treated with anti-vascular endothelial growth factor (anti-VEGF). Patients and Methods: This retrospective cohort study of 116 eyes with edema secondary to RVO characterized early responders (ER) and LER 3 months after initiating anti-VEGF treatment. Baseline characteristics and 12-month outcomes were compared. A machine learning (ML) algorithm was developed to predict LER. Results: At baseline, LER had higher best-corrected visual acuity (BCVA) than ER ( P < 0.0001) and lower central subfield thickness (CST) than ER ( P < 0.01). At 12 months, change in BCVA was + 0.8 and + 21.4 letters, and change in CST was −104.4 and −187.1 μm for LER and ER, respectively ( P < 0.0001, P < 0.05). The ML algorithm achieved area under the receiver operating characteristic curve = 0.73. Conclusion: ER eyes experienced greater functional and anatomical improvements at 12 months in routine clinical practice than LER. The ML algorithm achieved moderately high performance predicting LER. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:231–237.]

Background and Objective: This study explores the connection between macular atrophy (MA) status at baseline and best visual acuity (BVA) after 5 to 7 years of anti-vascular endothelial growth factor (anti-VEGF) injections on eyes with neovascular age-related macular degeneration (nAMD). Patients and Methods: This retrospective study included patients with neovascular age-related macular degeneration receiving anti-VEGF injections at least twice-yearly for 5+ years at Cole Eye Institute. Analyses of variance and linear regressions explored the connection between MA status, baseline MA intensity, and 5-year BVA change. Results: Of 223 included patients, 5-year BVA change was not statistically significant between MA status groups or from baseline. The population's average 7-year BVA change was −6.3 Early Treatment Diabetic Retinopathy Study letters. Type and frequency of anti-VEGF injections were comparable between MA status groups ( P > 0.05). Conclusion: Regardless of MA status, 5- and 7-year BVA change lacked clinical relevance. If receiving regular treatment for 5+ years, patients with baseline MA achieve comparable visual outcomes to those without MA, with similar treatment and visit burdens. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:223–230.]

To evaluate the anatomic and visual outcomes of patients with idiopathic epiretinal membranes (ERM) complicated by schisis of the retinal nerve fiber layer (sRNFL) in routine clinical practice.Retrospective case control study.Patients undergoing idiopathic ERM surgery at Cole Eye Institute from 2013-2021.Patients were grouped by the presence of absence of sRNFL prior to surgery. Preoperative and postoperative data was collected regarding VA, changes in central subfield thickness (CST) over time, and presence of cystoid macular edema (CME).Frequency of sRNFL in patients undergoing idiopathic ERM surgery.48 of 89 patients (53.9%) presented with sRNFL. sRNFL patients presented with significantly decreased VA compared to those without (58.63 ± 12.48 vs 67.68 ± 7.84 ETDRS letters, p0.001 respectively). At final follow-up after ERM removal, there was no significant difference in final VA in sRNFL patients compared to those without (71.16±2.93 vs 74.11±2.76, p=0.467). At presentation, sRNFL patients had greater CST than those without (454±10.01 vs 436±0.23, p=0.23). This difference persisted at 90-day follow-up after ERM removal (402 ± 8.08 vs 375± 10.19 μm, p=0.043). Resolution of sRNFL was reported at post-operative week 1 in 30 of 31 cases (96.7%).SRNFL is a microstructural feature in greater than 50% of idiopathic ERMs in routine clinical practice and carries visual significance on presentation and anatomic significance postoperatively.

Background and Objectives: To pool available data on the change in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and number of injections as reported by treat and extend (T&E) and pro re nata (PRN) regimens for retinal vein occlusion (RVO). Materials and Methods: After PubMed was queried, separate random effect models were fitted to the data extracted and the Wald test was used to compare the estimates of the two independent meta-analyses. Results: Fourteen T&E and 29 PRN studies were included in two independent meta-analyses. No significant difference was observed in BCVA (+14.74 [+11.52, +17.96] in T&E vs +15.90 [+14.24, + 17.56] in PRN, P = 0.530) or CRT improvements (−259.56 [−189.02, −330.09] in T&E vs −256.58 [−226.57, −286.48] in PRN, P = 0.939). More injections over 12 months were observed in T&E regimens (7.48 [6.32, 8.65] vs 5.13 [4.20, 6.06] in PRN, P = 0.002). Conclusion: Although more injections may be required, T&E achieves similar functional and anatomic benefits as compared to PRN regimens. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:244–250.]

Purpose: To characterize the rate of COVID-19 positivity during presurgical screening and the surgical outcomes of ophthalmic patients who were positive for COVID-19 and to report the overall cost. Methods: This retrospective study included patients 18 years or older who had ophthalmic surgical procedures at a tertiary institution between May 11, 2020, and December 31, 2020. Patients without a valid presurgical COVID-19 test within 3 days before their scheduled procedure, who had incomplete or mislabeled visits, or who had incomplete or missing data in their file were excluded. COVID-19 screening was completed using a polymerase chain reaction (PCR) kit. Results: Of the 3585 patients who met the inclusion criteria, 2044 (57.02%) were women; the mean age was 68.2 years ± 12.8 (SD). Thirteen asymptomatic patients (0.36%) tested positive for COVID-19 via PCR screening. Three patients had a known positive COVID-19 infection within the 90 days before surgery; thus, 10 patients (0.28%) were found to have asymptomatic naïve COVID-19 infection via PCR testing. Testing was associated with a total charge of US $800 000. Five of the 13 patients (38.46%) who tested positive for COVID-19 experienced a delay in their surgery; the mean delay was 17.23 ± 22.97 days. Conclusions: Asymptomatic ophthalmic surgical patients had a low positivity rate with a limited impact on surgery scheduling at a significant cost. Further studies would be valuable in evaluating a targeted presurgical screening population as opposed to universal testing.

Purpose: Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of age-related macular degeneration (AMD). Oxidized mitochondrial flavoprotein fluorescence (FPF) may serve as a quantifiable biomarker of oxidative stress, reported as either mean score for the entire image (intensity) or variability (heterogeneity). This study examines FPF intensity and heterogeneity across a large patient cohort of various Beckman stages of AMD. Methods: This study enrolled patients with isolated AMD and healthy control patients with no retinopathy between 2018 and 2021. Multivariate logistic regression analysis included stage of AMD, age, gender, ethnicity, and smoking status. Analysis of Variance test compared mean FPF intensity and heterogeneity between disease states. Results: Four hundred fifty-six eyes (228 AMD eyes, 228 age-matched control eyes) were included in the final multivariate analysis. Intermediate, geographic atrophy (GA), and neovascular AMD correlated with significantly increased FPF intensity ( P < 0.001, respectively), while all AMD stages correlated with increased FPF heterogeneity ( P < 0.001, respectively). FPF intensity and heterogeneity were significant negative predictors of visual acuity ( P = 0.018 and 0.024, respectively). Conclusions: This prospective observational study further implicates mitochondrial damage in AMD pathophysiology. Long-term clinical trials will be needed to examine the predictive role of FPF imaging in patients over time. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:24–31.]

Purpose: To assess the short-term and long-term effects of a delay in care on visual acuity (VA) in patients requiring intravitreal injections. Methods: This retrospective cohort study comprised patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) receiving intravitreal injections. The visual and anatomic outcomes at the next completed visit and at the 1-year follow-up were studied. Results: Of 1172 patients, 38% had a delay in care (mean 5.7 weeks). Compared with baseline, these patients lost VA (Early Treatment Diabetic Retinopathy Study letters) (mean −2.13 ± 0.49 SE) in the short-term ( P = .0003) and had a thicker central subfield. Patients with no delay in care had a net VA gain (0.97 ± 0.39) ( P = .0067). There was no difference in VA between 1 year and the baseline in either group. Long term, patients with nAMD in both groups had VA loss (no delay in care: −1.76 ± 0.60; delayed care: −2.44 ± 0.78) ( P = .0005 and P = .0114, respectively). Patients with DME and no delay in care maintained gains in vision (4.68 ± 1.86) but those with delayed care did not (1.72 ± 2.24) ( P = .0202 and P = .3756, respectively). In both groups, patients with RVO had no significant difference in vision from baseline. Conclusions: In patients requiring intravitreal injections, a delay in care of 5.7 weeks affected vision outcomes in the short term but not the long term.

Background and Objective: Macular involvement is considered a poor prognostic factor for visual recovery after rhegmatogenous retinal detachment (RRD) repair. Few prior studies report outcomes longer than 2 years after repair with pars plana vitrectomy (PPV) or combined PPV/scleral buckle (SB). The purpose of this study is to evaluate long-term (at least 5 years) visual outcomes following fovea-involving RRD repair with PPV or PPV/SB. Patients and Methods: This retrospective case series evaluated eyes that underwent fovea-involving RRD repair with PPV or PPV/SB. Eyes with single surgery anatomic success and 5 years or more of follow-up were included. Eyes with other ophthalmic pathology affecting central vision were excluded. Paired analysis compared changes in best visual acuity (BVA) between two timepoints. Results: Fifty-one eyes were included. Median (interquartile range, IQR) time to final follow-up was 7 (IQR: 3) years. Median pre-operatively BVA was 19.95 (IQR: 41.25) letters and improved to 80.15 (IQR:15.05) letters and 80.16 (IQR: 8.80) letters at the 1-year and final follow-up, respectively ( P < 0.001). Thirteen of 45 eyes (28.89%) had an improvement in BVA of at least 10 letters from the 1-year to the final follow-up. Average BVA was 20/40 or better in 35/45 eyes (75.56%) at 1-year and 45/51 eyes (88.24%) at final follow-up. No eye had an average BVA of 20/200 or worse at final follow-up. Conclusions: Patients with fovea-involving RRD successfully repaired with PPV or PPV/SB have favorable long-term visual acuity outcomes. BVA may continue to significantly improve even beyond 1 year after surgery. The majority of patients have a BVA of 20/40 or better 5 years after surgery. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:674–680.]

Background and Objective: Rhegmatogenous retinal detachment (RRD) requires urgent surgical intervention. The effect of travel distance on RRD outcomes is unclear. Patients and Methods: This retrospective cohort study included 642 patients who underwent RRD repair at Cole Eye Institute from 2012 to 2020. Google Maps was used to calculate the travel distance in miles from the residential zip code to the presenting and surgery location addresses. Multivariable logistic and bivariate linear regressions were used to compare macula-off status and best-corrected visual acuity (BCVA) in ETDRS letters at presentation and at 6-month follow-up, with patient travel distance divided into < 25 miles, 25 to 50 miles, and > 50 miles. Results: Four hundred sixty-two patients were examined in the final cohort. The retinal reattachment rate was 94.3% for less than 25 miles, 96.3% for 25 to 50 miles, and 95.9% for greater than 50 miles ( P = 0.63). In multivariable analysis, distance to presenting location was not associated with macula-off status ( P = 0.69) or BCVA at follow-up ( P = 0.27). Oneway analysis of distance and time from presentation to surgery in days revealed that distance to surgical site was associated with longer time to surgery ( P = 0.003). Subset analysis of patients with income less than $25,520 ( n = 18) revealed greater distance to presenting and surgical location was associated with longer time to surgery ( P < .0001), but was not associated with BCVA at follow-up ( P = 0.53). Conclusions: This data suggests that patients who live further from the hospital achieve equivalent outcomes from RRD repair, despite delays in surgery. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:666–672.]

Neovascular age-related macular degeneration (nAMD) often requires intensive therapy with anti-VEGF injections. In prior post hoc studies, early residual fluid (ERF) after the loading phase was associated with poorer treatment outcomes. This retrospective study examined the impact of ERF on vision using machine learning (ML) methods in routine clinical practice.Retrospective cohort.This study included treatment-naïve patients with nAMD who were initiated on anti-VEGF between 2012 and 2018, with at least 1 year of follow-up.Overall, 286 patients with nAMD were included. An ML algorithm quantified intraretinal fluid (IRF), subretinal fluid (SRF), and total retinal fluid from OCTs. The ERF group included those with fluid at week 12 and was further stratified by fluid subtype. Paired t tests and analysis of variance compared best visual acuity (BVA) and fluid among subgroups, and a quartile analysis correlated fluid volumes to week 52 BVA. The risk of ERF was predicted from baseline factors using 3 ML methods: Ridge logistic regression, k nearest neighbors classification, and support vector classification.Mean change in BVA from baseline to week 52 according to week 12 fluid status.At week 12, 58.4% of patients had ERF. The breakdown of those in the ERF group included SRF-only (45.5%), IRF-only (21.6%), and IRF and SRF (32.9%). The ERF and ERF-free groups had similar BVA gains from baseline to week 52 (+5.7 ± 15.4 vs. +4.9 ± 18; P = 0.69). Examining specific ERF subgroups revealed no significant differences among the IRF-only (+4.6 ± 16.4), SRF-only (+5.6 ± 12.5), and IRF and SRF (+6.6 ± 18.5, P = 0.93) groups. Quartile analysis of week 12 fluid revealed no predictive pattern for BVA gains. Three ML methods were developed to predict those at risk for ERF achieved equivalent performance, with F1 score of 0.73 to 0.76.These results diverge from prior post hoc studies, in that there was no significant difference in long-term BVA gains between ERF and ERF-free cohorts, as well as between the week 12 fluid subgroups.

BACKGROUND AND OBJECTIVE: To characterize treatment patterns for retinal vein occlusion (RVO)-related macular edema (ME) in routine clinical practice and its impact on long-term best-corrected visual acuity (BCVA) and central subfield thickness (CST). PATIENTS AND METHODS: Retrospective study of 365 eyes with branch RVO (BRVO) or central/hemi-RVO (CRVO/HRVO)-related ME between 2003 and 2020. Regression analysis identified factors associated with maintenance injection interval (MII). Subgroup analysis compared outcomes between different MIIs. RESULTS: 51.3% of BRVO patients received injections ≤q8 weeks, 26.4% received injections q8-12 weeks, and 22.3% received injections >q12 weeks. 45.2% of CRVO/HRVO patients received injections ≤q8 weeks, 32.1% received injections q8-12 weeks, and 22.6% received injections >q12 weeks. Age, diabetes, and baseline CST were found to predict MII. There was no significant difference in BCVA and CST at baseline, 12, or 24 months in all MII groups in BRVO and CRVO/HRVO. CONCLUSION: There exists a significant heterogeneity in anti-VEGF treatment frequency for RVO-associated ME in routine clinical practice. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:626–633.]

Fluid in neovascular age-related macular degeneration is often used to assess patient response to anti-vascular endothelial growth factor therapy. Various studies theorize that early residual fluid (ERF), noted as persistence of intraretinal fluid and subretinal fluid after the anti-vascular endothelial growth factor loading phase (LP), may be predictive of visual outcomes. This meta-analysis examined the existing literature on the relationship between ERF and long-term visual acuity (VA) and found that those who were fluid-free after the LP tended to have the highest VA gains overall. Early intraretinal fluid appeared to be associated with reduced VA gains, whereas the impact of early sub-retinal fluid was more debated. For those with ERF, monthly or more frequent dosing regimens following the LP appeared most optimal for VA. As most studies in this review were post hoc analyses, this highlights the need for real-world studies investigating ERF and its effect on visual outcomes in neovascular age-related macular degeneration. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:506–513.]

Both traumatic and nontraumatic ocular issues often present to the emergency department. Understanding the epidemiology of ocular presentations to the emergency department not only informs current resource allocation, but also provides opportunities to evaluate the efficacy of prior healthcare access interventions.To characterize emergency department utilization in the United States for ophthalmic encounters between 2010 and 2018.Cross-sectional analysis of the National Hospital Ambulatory Medical Care Survey database, a nationally representative sample of United States emergency department visits. 4284 deidentified emergency department patient encounters with an ICD-10 ophthalmic diagnosis from 2010 to 2018 were analyzed. The main outcome measures were the composition and characteristics of ophthalmic emergency department encounters over time.4284 ophthalmic visits were identified which represented an estimated 23.1 million visits (95% CI, 20.8 million-25.5 million). 31.6% (95% CI, 29.6-33.8) of ophthalmic visits were traumatic. Conjunctivitis was the most common non-traumatic diagnosis (32.8%, 95% CI, 30.7-35.0), while superficial injury of the cornea was the most common traumatic diagnosis (13.9%, 95% CI, 12.5-15.3). A greater proportion of emergency department visits involving the sclera and cornea were made by men (58.7%, 95% CI, 53.7%-63.6%; P = 0.02), whereas more women visited for visual disturbances (57.8%, 95% CI, 51.3%-64.4%; P = 0.01). Longitudinal trends of ophthalmic visits revealed an increase in public insurance payers in 2014, which corresponds to Medicaid expansion and implementation of mandated coverage for pediatric vision care. After stratification, this increase continued to be present in nontraumatic visits, but not traumatic ones.Ophthalmic emergency department visits in the United States between 2010 and 2018 were typically for non-traumatic eye issues. Diagnoses varied greatly by patient demographics, such as age and gender. Understanding these variations is valuable for preparing emergency departments for ocular presentations and providing guidance for future practice.

BACKGROUND AND OBJECTIVE: The objective is to validate an automated artificial intelligence model in detecting and quantifying fluid in diabetic macular edema (DME) and retinal vein occlusion (RVO) optical coherence tomography images. PATIENTS AND METHODS: DME ( n = 100) and RVO ( n = 100) images of adult patients were reviewed. The performance of machine-learning (ML) computational image analysis algorithm was evaluated against consensus manual grading. Main outcomes were accuracy and sensitivity for detection and Pearson's correlation coefficients for quantification. RESULTS: The ML algorithm had a high accuracy and sensitivity in both DME (intraretinal fluid [IRF]: 0.92, 0.97; subretinal fluid [SRF]: 0.93, 1.00) and RVO (IRF: 0.94, 0.99; SRF: 0.93, 1.00). It had moderate-high correlation in quantifying fluid in DME (total retinal fluid: 0.88; IRF: 0.88; SRF: 0.97) and RVO (total retinal fluid: 0.83; IRF: 0.76; SRF: 0.64). CONCLUSION: The ML algorithm is highly accurate and sensitive in detecting fluid in DME and RVO optical coherence tomography images and effectively quantifies IRF and SRF in both disease states, particularly in images with low to moderate fluid burden. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53:123–131.]

Background: Retinal diseases, including wet or dry age-related macular degeneration, diabetic macular edema, and diabetic retinopathy (DR), are underdiagnosed and undertreated in the United States. Clinical trials support the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) therapies for several retinal conditions, but real-world data suggest underuse by clinicians, resulting in patients experiencing poorer visual outcomes over time. Continuing education (CE) has demonstrated effectiveness at changing practice behaviors, but more research is needed to understand whether CE initiatives can help address diagnostic and treatment gaps for patients with retinal diseases in the long-term. Methods: This case-control study analyzed pre-/post-test knowledge of retinal diseases and guideline-based screening and intervention among 10,786 healthcare practitioners who participated in the modular, interactive CE initiative VISION RELIEF. An additional medical claims analysis by IQVIA provided data on practice change, evaluating use of VEG-A inhibitors among retina specialist and ophthalmologist learners (n=7,827) pre-/post-education, compared to a matched control group of non-learners. Outcomes were pre-/post-test change in knowledge/competence and clinical change in application of anti-VEGF therapy, as identified by the medical claims analysis. Results: Learners from all disciplines significantly improved knowledge/competence scores on items relating to early identification and treatment, identifying patients who could benefit from anti-VEGF agents, using guideline-recommended care, recognizing the importance of screening and referral, and recognizing the importance of early detection and care for DR (all P-values=0.003 to 0.004). Compared with matched controls, learners’ incremental total injections for anti-VEGF agents utilized for retinal conditions increased more after the CE intervention (PPConclusions: This modular, interactive, immersive CE initiative resulted in significant knowledge/competence gains among a nationwide sample of retinal disease care providers and changes in practice-related treatment behaviors (i.e., appropriate consideration and greater incorporation of guideline-recommended anti-VEGF therapies) among participating ophthalmologists and retina specialists compared to a carefully matched control. Future studies will utilize medical claims data to show longitudinal impact of this CE initiative on treatment behavior among specialists as well as its impact on diagnosis and referral rates among optometrists and primary care providers who participate in future programming.

Purpose To assess the availability and content of fellowship program Web sites (FPWs) among ophthalmology subspecialties. Design This is a cross-sectional study. Subjects Web sites of all Association of University Professors of Ophthalmology-accredited fellowship programs in five subspecialties (i.e., surgical retina and vitreous; cornea, external disease, and refractive surgery; glaucoma; neuro-ophthalmology; and pediatric ophthalmology). Methods FPWs were assessed for the presence of 26 key content criteria encompassing program demographics (n = 13), features (n = 10), and social life (n = 3). The presence of each content criterion as well as the content criteria groups were compared across subspecialties. Main Outcome Measures The main outcome measured is the average percentage of key content criteria present among ophthalmology fellowship Web sites. Results Among 266 accredited fellowship programs, 240 (90.2%) had Web sites. On average, Web sites reported 14.9 of 26 key content criteria (57.2%), 8.29 of 13 demographic criteria (63.8%), 5.84 of the 10 program features criteria (58.4%), and 0.705 of the 3 social life criteria (23.5%). Significant differences were identified among subspecialties in the presence of program description (p = 0.046), hospital affiliation (p Conclusion There is significant heterogeneity in program fellowship Web site content among ophthalmology subspecialties. Information regarding social life, such as wellness programs and community information, was largely absent across all disciplines. Addressing missing information on ophthalmology FPWs may help optimize program-applicant fit.

PRECIS Adjusting for sociodemographics and comorbidities, patients with glaucoma incur an annual incremental economic burden of $1863.17, translating to $9.2 billion nationally. When analyzed by the health care service sector, prescription medication expenditures were higher for glaucoma patients. PURPOSE The purpose of this study was to estimate the incremental health care burden, defined as attributable costs solely due to a diagnosis, of patients with diagnosed glaucoma, controlling for comorbidities, and sociodemographics. DESIGN A retrospective cross-sectional analysis of Medical Expenditure Panel Survey (MEPS) participants (age above 18 y) between 2016 and 2018. METHODS A cross-validated 2-part generalized linear regression model estimated the incremental glaucoma expenditures in aggregate and by sociodemographic subgroups and health care service sector [inpatient, outpatient (including surgical procedures), emergency room, home health, and medications] after 1:3 propensity matching. RESULTS After 1:3 propensity matching for sociodemographics and the Charlson Comorbidity Index, this study analyzed 1521 glaucoma patients (mean expenditures: $13,585.68±1367.03) and 4563 patients without glaucoma (mean expenditures: $12,048.92±782.49). A higher proportion of glaucoma patients are female, elderly, publicly insured (Medicare/Medicaid), college educated, identify ethnically as non-Hispanic, reside in the Northeast, and have more comorbidities (P

In eyes with neovascular AMD, early persistent retinal dryness response to anti-VEGFs was associated with clinically relevant improvements in vision-related function and a greater visual acuity gain compared with when intraretinal fluid was present.

BACKGROUND AND OBJECTIVE: Although people of low socioeconomic status (SES) and certain racial groups are at greater risk of developing diabetic macular edema (DME), the extent these high-risk groups experience treatment differences is unknown. This study characterizes anti-vascular endothelial growth factor (anti-VEGF) injection use for DME. PATIENTS AND METHODS: Data were collected from an electronic health record at the Cole Eye Institute, Cleveland Clinic Foundation for patients who received anti-VEGF treatment for DME between 2012 and 2019 ( N = 500). RESULTS: White patients on average received more injections over a 1-year period than Black patients (4.93 ± 3.14 vs 3.20 ± 2.43; P < .0001) and had fewer no-show appointments (1.39 ± 2.08 vs 3.23 ± 3.39; P < .0001). There is an association between living in communities with lower average incomes and receiving fewer anti-VEGF injections (3.06 ± 2.70 vs 4.88 ± 3.19; P = .005). CONCLUSIONS: DME treatment differs based on race and SES. Racial and SES associations with anti-VEGF injections present potential obstacles for delivering optimal ophthalmic care. [ Ophthalmic Surg Lasers Imaging Retina. 2021;52:578–585.]

Background As higher-valent PCVs are currently in late-stage clinical development for pediatric use, it is important to understand how healthcare providers (HCPs) evaluate vaccine attributes when making recommendations for newer PCVs. The Advisory Committee on Immunization Practices considers feasibility and stakeholder acceptability in making vaccine recommendations; this study examined HCP preferences and attitudes towards new, higher-valent PCVs in children in the US. Methods Semi-structured qualitative interviews were conducted with 13 HCPs (6 pediatricians, 3 family practitioners, 3 nurse practitioners, and 1 physician assistant). US HCPs were recruited from an online panel and were eligible if they recommended or prescribed vaccines to children ≤ 2 years and spent ≥ 2 days a week providing care to pediatric patients. Providers were asked to rate a list of PCV attributes (generated by literature search) by their importance in influencing their PCV choices (1, not important; 10, most important). Interviews were recorded, transcribed, and analyzed. Results Among HCPs (mean age=49 years; 62% women; 38% urban, 38% suburban; mean years in practice=18 years), three main themes emerged: 1) Preferred attributes: The three most important PCV characteristics that affect HCPs’ recommendations are effectiveness against serotype 3 (rated 9.1), percent serotype coverage for invasive pneumococcal disease (IPD) (rated 8.9), and immune response for the shared PCV13 serotypes (rated 8.2). 2) PCV choice: Most respondents are interested in having more PCV options, particularly options with higher efficacy or broader serotype coverage. 3) Immunogenicity vs serotype coverage: Between a higher immune response to certain serotypes and broader serotype coverage, 46% of HCPs prefer PCVs that elicit a higher immune response but narrower coverage, 31% prefer a PCV with broader serotype coverage, and 23% require more data before making a determination. Conclusion Both immune response and breadth of serotype coverage may influence HCPs decisions when recommending new PCVs. Additional analyses and interviews are underway to validate these findings and further explore other factors that may influence their preferences for recommending PCVs. Disclosures Salini Mohanty, DrPH, MPH, Merck & Co., Inc.: Employee Jui-Hua Tsai, MD, MHS, OPEN Health: Employee of OPEN Health, which received funding from Merck & Co., Inc. to conduct this research Ning Ning, PhD, MS, Open Health: I am an employee of OPEN Health, which received funding from Merck Ana Pena-Molina, MPH, OPEN Health: I am an employee of OPEN Health, which received funding from Merck Rishi P. Verma, MPH, OPEN Health: I am an employee of OPEN Health, which received funding from Merck Marieke Heisen, PhD, MSc, OPEN Health: I am an employee of OPEN Health, which received funding from Merck Jessica Weaver, PhD, MPH, Merck & Co., Inc.: Employee Kristen A. Feemster, MD, MPH, MSHPR, FAAP, Merck & Co., Inc.: Employee Thomas Weiss, DrPH, MPH, Merck & Co., Inc.: Employee Jordana Schmier, MA, OPEN Health: I am an employee of OPEN Health, which received funding from Merck.

Since COVID-19 vaccines became available, no studies have quantified how different disaster evacuation strategies can mitigate pandemic risks in shelters. Therefore, we applied an age-structured epidemiological model, known as the Susceptible-Exposed-Infectious-Recovered (SEIR) model, to investigate to what extent different vaccine uptake levels and the Diversion protocol implemented in Taiwan decrease infections and delay pandemic peak occurrences. Taiwan's Diversion protocol involves diverting those in self-quarantine due to exposure, thus preventing them from mingling with the general public at a congregate shelter. The Diversion protocol, combined with sufficient vaccine uptake, can decrease the maximum number of infections and delay outbreaks relative to scenarios without such strategies. When the diversion of all exposed people is not possible, or vaccine uptake is insufficient, the Diversion protocol is still valuable. Furthermore, a group of evacuees that consists primarily of a young adult population tends to experience pandemic peak occurrences sooner and have up to 180% more infections than does a majority elderly group when the Diversion protocol is implemented. However, when the Diversion protocol is not enforced, the majority elderly group suffers from up to 20% more severe cases than the majority young adult group., Comment: Supplementary information: https://drive.google.com/file/d/1Lc8QpeEYX4n7S_l9CZ2mrREa2e6MwnIC/view?usp=sharing

Whether by indirect oxidative stress or direct genetic defect, various genetic retinal dystrophies involve mitochondrial stress. Mitochondrial flavoprotein fluorescence (FPF), reported as either average signal intensity or variability (heterogeneity), may serve as a direct, quantifiable marker of oxidative stress.This observational study enrolled patients with genetically confirmed retinal dystrophies between January and December 2021. Patients with concomitant maculopathy and ocular hypertension were excluded. Patients were FPF imaged with OcuMet BeaconThe final analysis cohort included 242 images from 157 patients. Mean FPF intensity was significantly increased between age matched controls and patients with confirmed rod-cone dystrophy, Stargardt disease, Bardet-Biedl syndrome (BBS), and Mitochondrial ATP synthase mutation (FPF intensity and heterogeneity significantly increased in patients with retinal dystrophies. The correlation of FPF lesions with FAF lesions implies FPF may be a clinically useful biomarker in patients with IRDs.This study found increases in flavoprotein fluorescence signal in patients with genetically confirmed inherited retinal dystrophies compared to age matched controls. Flavoprotein fluorescence signal correlated with fundus autofluorescence findings, suggesting clinical utility of novel signal.

This study characterizes the association of risk factors including race, ethnicity, and insurance status with presenting visual acuity (VA) and diabetic retinopathy (DR) severity in patients initiating treatment with anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME).Retrospective, cross-sectional study.The Academy Intelligent Research in Sight (IRIS) Registry database was queried for patients who initiated anti-VEGF injection treatment for DME between 2012 and 2020 (n = 203 707).Multivariate regression analyses were conducted to understand how race, ethnicity, insurance status, and geographic location were associated with baseline features.Visual acuity and DR severity.Patients on Medicare and private insurance presented with higher baseline VA compared with patients on Medicaid (median of 2.31 and 4.17 greater Early Treatment Diabetic Retinopathy Scale [ETDRS] letters, respectively P0.01). White and non-Hispanic patients presented with better VA compared with their counterparts (median of 0.68 and 2.53 greater ETDRS letters, respectively; P0.01). Black and Hispanic patients presented with a worse baseline DR severity compared with White and non-Hispanic patients (odds ratio, 1.23 and 1.71, respectively; P0.01).There are ethnic and insurance-based disparities in VA and disease severity upon initiation of anti-VEGF therapy for DME treatment. Public health initiatives could improve timely initiation of treatment.

BACKGROUND AND OBJECTIVE: To evaluate coronavirus disease 2019 (COVID-19) cases as of February 1, 2021 and the proportion of ophthalmologists in the United States older than age 60 years to provide a framework for successful vaccine distribution for the ophthalmology workforce. PATIENTS AND METHODS: The Association of American Medical Colleges ophthalmologist workforce dataset (from 2019) for each state was combined with John Hopkins University's COVID-19 tracking data to determine exposure risk for ophthalmologists, especially those older than age 60 years. RESULTS: Of the 18,915 practicing ophthalmologists in the US, 37.6% are older than age 60 years. North Dakota (48.4%), Connecticut (46.8%), and Maine (46.7%) have the highest percentages. South Dakota (9,567), Utah (7,559), and Idaho (7,411) currently have the highest COVID-19 exposure burden per ophthalmologist older than age 60 years as of February 1, 2021. CONCLUSION: Care must be taken to distribute the COVID-19 vaccine in a safe and proactive manner to ophthalmologists that face high exposure risk, both to ensure physician safety and ensure adequate care for the population they serve. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:556–559.]

Purpose To examine the effect of delay in care on visual acuity (VA) in patients requiring intravitreal injections (IVIs). Design Retrospective cohort study. Participants Patients 18 years of age or older with diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), or both; neovascular age-related macular degeneration (nAMD); or retinal vein occlusion (RVO) scheduled to see a retina specialist during the mandated lockdown period (March 14 - May 4, 2020 [the coronavirus disease 2019 period]) and who had received an IVI in the 12 weeks prior. Methods Chart review was performed and demographics, diagnoses, procedures, and VA were recorded. Main Outcome Measures VA in patients who completed, canceled, and no-showed for the scheduled visit. Results Of the 1041 total patients, 620 (60%) completed the scheduled visit, whereas 376 (36%) canceled and 45 (4%) no-showed. In patients who missed the visit, the average delay in care was 5.34 weeks. In those who missed a visit, VA was assessed at the subsequent visit. Patients who canceled a visit were older, and patients who no-showed had lower baseline vision (mean Early Treatment Diabetic Retinopathy Study letters ± standard error [SE]: no-show, 53.27 ± 3.21 letters; canceled, 60.79 ± 1.11 letters; and completed, 62.81 ± 0.84 letters; P = 0.0101) and were more likely to have DME, PDR, or both (no-show, 13 patients [29%]; canceled, 56 patients [16%]; completed, 81 patients [13%]; P = 0.0456). Patients who missed a visit lost vision as compared with the patients who completed one (no-show, –5.024 ± 1.88 letters; canceled, –1.633 ± 0.65 letters; completed, 0.373 ± 0.50 letters; P = 0.0028). Patients with DME, PDR, or both (–3.48 ± 1.95 letters vs. 2.71 ± 1.75 letters; P = 0.0203), with RVO (–3.22 ± 1.41 letters vs. 0.95 ± 1.23 letters; P = 0.0230), and, to lesser degree, with nAMD (–1.23 ± 0.70 letters vs. –0.24 ± 0.56 letters; P = 0.2679) lost vision compared with patients with same diagnoses who completed the scheduled visit. Conclusions In patients requiring IVIs, a delay in care of 5.34 weeks resulted in vision loss. It was seen in all patients, but was more prominent in patients with DME, PDR or both and RVO. Further studies are necessary to examine whether these vision changes persist over a longer duration.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the necessity of the postoperative day-1 (POD1) review after pars plana vitrectomy. PATIENTS AND METHODS: The analysis included available literature that documented medical and surgical interventions performed on POD1 review after pars plana vitrectomy. A meta-analysis of proportions was conducted using a binomial-normal model to analyze three data sets consisting of all interventions, medical interventions, and surgical interventions. Heterogeneity and publication bias analyses were performed. RESULTS: POD1 reviews of 2,262 patients across 14 studies were examined to yield a total POD1 intervention rate estimate of 4.7% (95% confidence interval [CI], 3.0–13.9). When stratified by medical or surgical intervention, the intervention rate estimates were 4.1% (95% CI, 1.4–11.6) and 0.7% (95% CI, 0.3–1.3), respectively. The most common complication requiring postoperative intervention was elevated intraocular pressure. CONCLUSION: Given the wide confidence intervals of the estimated intervention rates, variability in postoperative practices, and range of interventions performed, the POD1 review cannot be discarded in its entirety. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:513–518.]

To evaluate clinical characteristics of eyes in which investigator-determined new-onset exudative age-related macular degeneration (eAMD) developed during the FILLY trial.Post hoc analysis of the phase 2 study of intravitreal pegcetacoplan in geographic atrophy (GA).Patients with GA secondary to age-related macular degeneration (AMD), n = 246.Either 15 mg intravitreal pegcetacoplan or sham given monthly or every other month for 12 months followed by a 6-month off-treatment period.Time of new eAMD onset in the study eye, history of eAMD in the fellow eye, presence of double-layer sign (DLS) on structural OCT in the study eye, changes in retinal anatomic features by structural OCT and fluorescein angiography (FA), and changes in visual acuity.Exudation was reported in 26 study eyes across treatment groups over 18 months. Mean time to eAMD diagnosis was 256 days (range, 31-555 days). Overall, a higher proportion of patients with a baseline history of eAMD in the fellow eye (P = 0.016) and a DLS in the study eye (P = 0.0001) demonstrated eAMD. Among study eyes in which eAMD developed, 18 of 26 (69%) had history of fellow-eye eAMD and 19 of 26 (73.1%) had DLS at baseline, compared with 76 of 217 study eyes (35%; P = 0.0007) and 70 of 215 study eyes (32.5%; P0.0001), respectively, in which eAMD did not develop. All 21 patients with structural OCT imaging at the time of eAMD diagnosis demonstrated subretinal fluid, intraretinal cysts, or both consistent with exudation. Among 17 patients who underwent FA at eAMD diagnosis, 10 showed detectable macular neovascularization (MNV), all occult lesions. Development of eAMD did not have an appreciable impact on visual acuity, and all patients responded to anti-vascular endothelial growth factor (VEGF) therapy.Intravitreal pegcetacoplan slowed the rate of GA growth and was associated with an unexpected dose-dependent increased incidence of eAMD with no temporal clustering of onset. Exudative AMD seemed to be associated with baseline eAMD in the contralateral eye and a DLS, suggestive of nonexudative MNV, in the study eye. The safety profile of pegcetacoplan was acceptable to proceed to phase 3 studies without adjustments to enrollment criteria.

Gold-rich rare earth intermetallic compounds (viz. Ce2Au2Cd and CeAu4Cd2) show unusual magnetic and physical properties, and they have extensive applications in electronic and mechanical industries due to their good electronic and thermal behavior with high mechanical strength. In the present research article, to take full advantage of technological importance of these materials, we have investigated the structural, electronic and thermodynamic properties of Ce2Au2Cd and CeAu4Cd2 ternary intermetallic compounds using density functional theory (DFT). The electronic band structure and density of state calculations show that Ce-f orbital electrons provide metallic character to both the compounds with strong hybridization of Au-p and Cd-p orbitals at the Fermi level. The effect of temperature has been studied on the various thermodynamic parameters using the quasi-harmonic Debye model. Thermodynamic properties show that CeAu4Cd2 compound has larger mechanical resistance (or high mechanical strength or hardness) and smaller randomness compared to Ce2Au2Cd with respect to temperature.

BACKGROUND AND OBJECTIVE: To characterize rhegmatogenous retinal detachment (RRD) presentation and repair outcomes by race and socioeconomic status. MATERIALS AND METHODS: Retrospective cohort one-center study of adults with a new RRD repair from 2012 to 2020. Logistic and linear regression analyses were conducted. RESULTS: 61.7% were male, 84.5% White and 9.4% Black (total n = 1092). 95.8% White and 94.2% Black patients had retinal reattachment ( P = .234). Macula-off status was more likely with Medicare/Medicaid than private insurance (OR 1.63, 95% CI 1.11 to 2.41, P = .014); and less likely with higher income (OR 0.88, CI 0.81 to 0.96, P = .003). Black patients had worse best visual acuity (BVA) at presentation and follow-up (follow-up −6.93 letters, CI −13.19 to −0.64, P = .031), and higher odds of postoperative ocular hypertension (OHTN) (OR 2.41, CI 1.28 to 4.60, P = .007). CONCLUSIONS: Despite equivalent retinal reattachment rates, Black patients have worse BVA, and are more likely to develop OHTN than White patients. Macula-off status is less likely in patients with higher income or private insurance. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:538–545.]

PURPOSE: To evaluate retinal thickness fluctuations in patients with diabetic macular oedema (DMO) treated with anti-vascular endothelial growth factor (anti-VEGF) injections. METHODS: Visual acuity (VA) and central subfield thickness (CST) were collected at baseline, 3, 6, 9 and 12 months. Retinal thickness fluctuation was quantified by standard deviation (SD) of CST across 12 months. A mixed effects regression model evaluated the relationship between CST SD and VA at 12 months. Multiple linear regression analysis was performed to investigate predictors of CST SD. RESULTS: Mean baseline and 12-month VAs were 63.5 ± 15.7 and 69.0 ± 13.8 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters (change = +5.1 ± 16.1 letters, p

Purpose The intravitreal injection (IVI) of pharmacologic agents is the most commonly performed ocular procedure and is associated with a host of complications. Most IVI-related complications data are derived from randomized controlled clinical trials, which report a high adverse event rate. The nature of these protocol-driven trials limit their applicability to the diverse circumstances seen in routine clinical practice. The goal of this study was to determine the prevalence of patient-reported IVI-related complications, their risk factors, and the manner in which patients sought treatment at a tertiary eye care center. Design Retrospective, institutional review board–approved study. Participants Forty-four thousand seven hundred thirty-four injections in 5318 unique patients at the Cleveland Clinic Cole Eye Institute from 2012 through 2016. Methods Intravitreal injection. Main Outcome Measures Complication occurrence within 15 days of injection. Results From 2012 through 2016, a total of 44734 injections were performed in 5318 unique patients. Overall, complication rates were low, representing 1.9% of all injections, with 1031 unique complications in 685 patients (12.9%). The most common minor complications, or those not requiring intervention, were irritation (n = 312) and subconjunctival hemorrhage (n = 284). The most common serious complications, or those requiring intervention, were corneal abrasion (n = 46) and iritis (n = 31). Most complications (66%) were managed adequately by a telephone or Epic (Epic Systems Corp., Verona, WI) electronic message encounter only. Importantly, no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication. However, a patient’s gender, age, number of previous injections, and provider strongly influenced the risk of patient-reported complications. Conclusions Overall, complication rates seen in routine clinical practice were low compared with clinical trial reporting. Providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. When performing an IVI, factors such as a patient’s gender, age, number of previous injections, and provider must be taken into account to ensure the best possible outcomes.

PURPOSE To characterize the true position of in-the-bag intraocular lenses (IOLs) relative to the limbus using ultrasound biomicroscopy and estimate scleral-sutured IOL positioning. METHODS This prospective single-center study included 70 eyes of 41 patients with in-the-bag posterior chamber IOLs. Four vertical ultrasound biomicroscopy captures were performed in each eye in the superior, inferior, nasal, and temporal quadrants. Postoperative biometric data were collected. The primary outcome was the vertical distance of the in-the-bag IOL from the sclerocorneal limbus. Secondary outcomes included anterior shift and refractive change of a theoretical scleral-sutured IOL using sclerotomies at 2.5 mm and 3 mm posterior to the limbus. RESULTS A total of 265 ultrasound biomicroscopy images were analyzed, including 64 superior, 69 inferior, 66 nasal, and 66 temporal. The true in-the-bag IOL position measured as distance posterior to the sclerocorneal limbus was 4.23 ± 0.56 mm superiorly, 4.22 ± 0.46 mm inferiorly, 3.95 ± 0.48 mm nasally, and 3.86 ± 0.52 mm temporally. The anterior shift of a theoretical scleral-sutured IOL was 0.60 mm for a 3-mm sclerotomy and 0.93 mm for a 2.5-mm sclerotomy, resulting in a theoretical myopic shift of 0.45 diopter (D) and 0.79 D, respectively, assuming a 15-D IOL. Larger biometric measurements correlated with a more posterior in-the-bag position. CONCLUSION True in-the-bag IOL position was found to be more posterior than estimates of scleral-sutured IOLs. Additional corrections in scleral-sutured IOL calculations may improve refractive outcomes.

Retinal fluid and thickness are important anatomical features of disease activity in neovascular age-related macular degeneration. This review describes how these anatomical features relate to the visual acuity and the efficacy of dosing regimens that make use of these features for determining dosing interval durations., Purpose: Retinal fluid and thickness are important anatomical features of disease activity in neovascular age-related macular degeneration, as evidenced by clinical trials that have used these features for inclusion criteria, retreatment criteria, and outcome measures of the efficacy of intravitreal injections of anti–vascular endothelial growth factor agents. Methods: A literature review of anatomical measures of disease activity was conducted. Results: Treatment goals for neovascular age-related macular degeneration include improving/maintaining vision by drying the retina, and several analyses have evaluated the relationship between visual function and anatomy. The change in retinal thickness has been found to correlate with the change in the visual acuity, and variation in retinal thickness may predict visual acuity outcomes. In addition, specific fluid compartments may have different prognostic values. For example, the presence of intraretinal fluid has been associated with poorer visual acuity, whereas the presence of subretinal fluid has been associated with better visual acuity. Retinal fluid and thickness are important for selecting dosing interval durations in clinical trials and clinical practice. Conclusion: Retinal thickness and retinal fluid are common anatomical measures of disease activity in neovascular age-related macular degeneration. Further research is required to fully elucidate the relationship between anatomical features and visual outcomes in neovascular age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To determine outcomes of eyes with diabetic macular edema (DME) and best visual acuity (BVA) of 20/25 or better in routine clinical practice. PATIENTS AND METHODS: Retrospective study of 72 patients with DME and BVA of 20/25 or better. Patients were divided by anti-vascular endothelial growth factor (VEGF) treatment regimen: early (Group A), delayed (Group B), and none (Group C). RESULTS: Group A had higher baseline central subfield thickness (CST) (325 ± 62 µm) compared to Groups B (292 ± 24 µm) and C (296 ± 35 µm) ( P = .033). All groups had similar 24-month CST (299 ± 62 µm, 280 ± 64 µm, 296 ± 65 µm; P = .61). There was no difference in baseline BVA among groups (81.9 ± 2.4, 83.2 ± 2.4, 82.4 ± 2.5 Early Treatment Diabetic Retinopathy Study [ETDRS] letters, respectively; P = .290), but at 6 months, Group A had lower BVA (76.6 ± 9.6 ETDRS letters) than groups B (81.9 ±3.3 ETDRS letters) and C (82.4 ± 5.0 ETDRS letters) ( P = .008). There was no difference among groups in 24-month BVA (78.9 ± 6.6, 78.4 ± 12.3, and 80.6 ± 6.9 ETDRS letters, respectively; P = .448). CONCLUSION: Although observation may be indicated in eyes with stable BVA and CST less than 300 µm, anti-VEGF stabilizes BVA in eyes with CST greater than 300 µm and eyes with declining BVA. [ Ophthalmic Surg Lasers Imaging Retina. 2021;52:247–256.]

BACKGROUND AND OBJECTIVE: To characterize on-label anti-vascular endothelial growth factor (VEGF) treatment patterns in patients with wet age-related macular degeneration (AMD) in clinical practice in the U.S. PATIENTS AND METHODS: Retrospective cohort analysis using administrative claims data from the IQVIA Open Source Databases. Treatment-naïve patients in the U.S. who received one or more wet AMD-related anti-VEGF injection from July 1, 2013, to April 30, 2017, were included. The main outcome was the injection interval closest to Month 12. RESULTS: This study included 21,960 patients who initiated an anti-VEGF agent (ranibizumab, aflibercept, or bevacizumab): 5,489 initiated aflibercept and 4,253 initiated ranibizumab. Among ranibizumab, aflibercept, and all anti-VEGF eyes, 38.1% (n = 2,035), 33.5% (n = 3,262), and 40.0% (n = 12,505) of patient eyes had injection intervals of less than 8 weeks, respectively, at Month 12 with the mean (standard deviation) number of injections over 12 months being 8.0 (2.4), 7.6 (2.4), and 7.8 (2.5). CONCLUSION: A substantial proportion of patients receive injections more frequently than every 8 weeks within the first year of treatment. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:263–272.]