Retinal changes after fluocinolone acetonide implant (ILUVIEN®) for DME: SD-OCT imaging assessment using ESASO classification.

INTRODUCTION: A detailed understanding of the anatomical and structural changes occurring in the retina following intravitreal fluocinolone acetonide implantation may help improve the management and prognosis of persistent or recurrent diabetic macular edema (DME). METHODS: Overall, 45 eyes (from 35 patients) with refractory center-involved DME received an intravitreal fluocinolone acetonide implant. They were monitored at baseline and at 6, 12, 24, and 36 months for best-corrected visual acuity (BCVA), central foveal thickness (CFT), and the seven retinal parameters used in the classification of diabetic maculopathy recently developed at the European School for Advanced Studies in Ophthalmology (ESASO). RESULTS: Within 6 months of implantation, significant improvements were evident in BCVA, CFT, maculopathy stage, and the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent ellipsoid zone (EZ) and/or external limiting membrane (ELM). Significant improvements were still maintained at 36 months post-implantation. At month 36, early treatment with the implant (i.e., after < 6 previous intravitreal injections for DME) trended toward being more effective than later treatment in improving BCVA, CFT, maculopathy stage, and the percentage of eyes with CFT > 30% above the upper normal value. However, statistical significance was not achieved. CONCLUSION: In persistent or recurrent DME, fluocinolone acetonide implantation can be effective in improving maculopathy stage and reducing the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent EZ and/or ELM. It can also increase BCVA and reduce CFT.

SGLT2 inhibitors and diabetic retinopathy progression.

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

Diagnostic Accuracy of Automated Diabetic Retinopathy Image Assessment Softwares: IDx-DR and Medios Artificial Intelligence.

INTRODUCTION: Numerous studies have demonstrated the use of artificial intelligence (AI) for early detection of referable diabetic retinopathy (RDR). A direct comparison of these multiple automated diabetic retinopathy (DR) image assessment softwares (ARIAs) is, however, challenging. We retrospectively compared the performance of two modern ARIAs, IDx-DR and Medios AI. METHODS: In this retrospective-comparative study, retinal images with sufficient image quality were run on both ARIAs. They were captured in 811 consecutive patients with diabetes visiting diabetic clinics in Poland. For each patient, four non-mydriatic images, 45° field of view, i.e., two sets of one optic disc and one macula-centered image using Topcon NW400 were captured. Images were manually graded for severity of DR as no DR, any DR (mild non-proliferative diabetic retinopathy [NPDR] or more severe disease), RDR (moderate NPDR or more severe disease and/or clinically significant diabetic macular edema [CSDME]), or sight-threatening DR (severe NPDR or more severe disease and/or CSDME) by certified graders. The ARIA output was compared to manual consensus image grading (reference standard). RESULTS: On 807 patients, based on consensus grading, there was no evidence of DR in 543 patients (67%). Any DR was seen in 264 (33%) patients, of which 174 (22%) were RDR and 41 (5%) were sight-threatening DR. The sensitivity of detecting RDR against reference standard grading was 95% (95% CI: 91, 98%) and the specificity was 80% (95% CI: 77, 83%) for Medios AI. They were 99% (95% CI: 96, 100%) and 68% (95% CI: 64, 72%) for IDx-DR, respectively. CONCLUSION: Both the ARIAs achieved satisfactory accuracy, with few false negatives. Although false-positive results generate additional costs and workload, missed cases raise the most concern whenever automated screening is debated.

Diabetic retinopathy screenings in West Virginia: an assessment of teleophthalmology implementation.

BACKGROUND: The prevalence of diabetes in the state of West Virginia (WV) is amongst the highest in the United States, making diabetic retinopathy (DR) and diabetic macular edema (DME) a major epidemiological concern within the state. Several challenges exist regarding access to eye care specialists for DR screening in this rural population. A statewide teleophthalmology program has been implemented. We analyzed real-world data acquired via these systems to explore the concordance between image findings and subsequent comprehensive eye exams and explore the impact of age on image gradeability and patient distance from the West Virginia University (WVU) Eye Institute on follow-up. METHODS: Nonmydriatic fundus images of diabetic eyes acquired at primary care clinics throughout WV were reviewed by retina specialists at the WVU Eye Institute. Analysis included the concordance between image interpretations and dilated examination findings, hemoglobin A1c (HbA1c) levels and DR presence, image gradeability and patient age, and distance from the WVU Eye Institute and follow-up compliance. RESULTS: From the 5,512 fundus images attempted, we found that 4,267 (77.41%) were deemed gradable.  Out of the 289 patients whose image results suggested DR, 152 patients (52.6%) followed up with comprehensive eye exams-finding 101 of these patients to truly have DR/DME and allowing us to determine a positive predictive value of 66.4%. Patients within the HbA1c range of 9.1-14.0% demonstrated significantly greater prevalence of DR/DME (p < 0.01).  We also found a statistically significant decrease in image gradeability with increased age.  When considering distance from the WVU Eye Institute, it was found that patients who resided within 25 miles demonstrated significantly greater compliance to follow-up (60% versus 43%, p < 0.01). CONCLUSIONS: The statewide implementation of a telemedicine program intended to tackle the growing burden of DR in WV appears to successfully bring concerning patient cases to the forefront of provider attention.  Teleophthalmology addresses the unique rural challenges of WV, but there is suboptimal compliance to essential follow-up with comprehensive eye exams. Obstacles remain to be addressed if these systems are to effectively improve outcomes in DR/DME patients and diabetic patients at risk of developing these sight-threatening pathologies.

Cost-effectiveness of Aflibercept Monotherapy vs Bevacizumab First Followed by Aflibercept If Needed for Diabetic Macular Edema.

Importance: The DRCR Retina Network Protocol AC showed no significant difference in visual acuity outcomes over 2 years between treatment with aflibercept monotherapy and bevacizumab first with switching to aflibercept for suboptimal response in treating diabetic macular edema (DME). Understanding the estimated cost and cost-effectiveness of these approaches is important. Objective: To evaluate the cost and cost-effectiveness of aflibercept monotherapy vs bevacizumab-first strategies for DME treatment. Design, Setting, and Participants: This economic evaluation was a preplanned secondary analysis of a US randomized clinical trial of participants aged 18 years or older with center-involved DME and best-corrected visual acuity of 20/50 to 20/320 enrolled from December 15, 2017, through November 25, 2019. Interventions: Aflibercept monotherapy or bevacizumab first, switching to aflibercept in eyes with protocol-defined suboptimal response. Main Outcomes and Measures: Between February and July 2022, the incremental cost-effectiveness ratio (ICER) in cost per quality-adjusted life-year (QALY) over 2 years was assessed. Efficacy and resource utilization data from the randomized clinical trial were used with health utility mapping from the literature and Medicare unit costs. Results: This study included 228 participants (median age, 62 [range, 34-91 years; 116 [51%] female and 112 [49%] male; 44 [19%] Black or African American, 60 [26%] Hispanic or Latino, and 117 [51%] White) with 1 study eye. The aflibercept monotherapy group included 116 participants, and the bevacizumab-first group included 112, of whom 62.5% were eventually switched to aflibercept. Over 2 years, the cost of aflibercept monotherapy was $26 504 (95% CI, $24 796-$28 212) vs $13 929 (95% CI, $11 984-$15 874) for the bevacizumab-first group, a difference of $12 575 (95% CI, $9987-$15 163). The aflibercept monotherapy group gained 0.015 (95% CI, -0.011 to 0.041) QALYs using the better-seeing eye and had an ICER of $837 077 per QALY gained compared with the bevacizumab-first group. Aflibercept could be cost-effective with an ICER of $100 000 per QALY if the price per dose were $305 or less or the price of bevacizumab was $1307 per dose or more. Conclusions and Relevance: Variability in individual needs will influence clinician and patient decisions about how to treat specific eyes with DME. While the bevacizumab-first group costs still averaged approximately $14 000 over 2 years, this approach, as used in this study, may confer substantial cost savings on a societal level without sacrificing visual acuity gains over 2 years compared with aflibercept monotherapy.

Comparison of Snellen Visual Acuity Measurements in Retinal Clinical Practice to Electronic ETDRS Protocol Visual Acuity Assessment.

PURPOSE: Evaluate the differences between clinical visual acuity (VA) as recorded in medical records and electronic Early Treatment Diabetic Retinopathy Study (eETDRS) protocol VA measurements and factors affecting the size of the differences. DESIGN: Retrospective chart review. PARTICIPANTS: Study and fellow eyes of participants enrolled in DRCR Retina Network Protocols AC and AE (diabetic macular edema), and W (nonproliferative diabetic retinopathy) with clinical VA recorded within 3 months before the protocol visit. METHODS: Differences and their association with patient and ocular factors were evaluated using linear mixed models with random effects for correlations within sites and participants. MAIN OUTCOME MEASURE: Difference between VA letter scores measured by eETDRS during a study visit versus measured by Snellen during a regular clinical visit (Snellen fraction converted to eETDRS). RESULTS: Data from 1016 eyes (511 participants) across 74 sites were analyzed. The mean VA measurements were 68.6 letters (Snellen equivalent 20/50) at the clinical visit and 76.3 letters (Snellen equivalent 20/32) at the protocol visit, with a mean (standard deviation [SD]) of 26 (21) days between visits. Mean (SD) protocol VA was better than clinical VA by 7.6 (9.6) letters overall, 10.7 (12.6) letters in eyes with clinical VA ≤ 20/50 (n = 376), and 5.8 (6.6) letters in eyes with clinical VA ≥ 20/40 (n = 640). On average, the difference between clinical and protocol VA was 1.3 letters smaller for every 1-line (5 letters) increase in clinical VA (P < 0.001). Mean (SD) differences by clinical correction of refractive error were 3.9 (9.0) letters with refraction, 6.9 (9.2) letters with glasses/contact lenses, 7.9 (11.5) letters with pinhole, and 9.8 (9.3) letters without correction (P = 0.06). CONCLUSIONS: On average, clinical Snellen VA is 1 to 2 lines worse than eETDRS protocol refraction and VA testing, which may partly explain why clinical practice does not always replicate clinical trial results. Eyes with lower clinical measurements and eyes tested without clinical refraction tended to have larger differences. Considering the potential discrepancies between clinical and protocol VA measurements, refracting eyes in the clinic may benefit patients when determining treatment plans and study referrals based on vision. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Aflibercept Monotherapy versus Bevacizumab-First for Diabetic Macular Edema: A Cost Analysis Based on Diabetic Retinopathy Clinical Research Network Protocol AC Results.

PURPOSE: To calculate the costs of treatment for diabetic macular edema with bevacizumab-first (step therapy) compared with aflibercept monotherapy. DESIGN: Cost analysis of the treatment arms based on a published study. SUBJECTS: None. METHODS: Published results from the Diabetic Retinopathy Clinical Research Network protocol AC were used to assess costs. Data incorporated in the usage and outcome model included the frequency of injections, medication type, visits, and imaging. Costs were modeled based on the 2022 Medicare reimbursement data for both facility (hospital-based) and nonfacility settings in Miami. Outcomes were similar in protocol AC so were not differentially studied. Results were extrapolated so as to estimate lifetime (17 years for the age of the cohort). MAIN OUTCOME MEASURES: Cost of treatment options. RESULTS: Over the 2 years reported in the protocol AC, the cost required to treat in the facility (nonfacility setting) was $42 000 ($32 000) in the aflibercept monotherapy group and $29 000 ($22 000) in the bevacizumab-first group. Extrapolated modeled lifetime costs were $158 000 ($136 000) and $125 000 ($103 000), respectively. The total cost with bevacizumab-first was 33% lower at year 2 and 21% lower at year 17 compared with aflibercept monotherapy. Savings per year for the 2 years results were $6500 ($5000) in the facility (nonfacility) setting. For the extrapolated 17 years model, annual savings were $1900 ($1900) in the facility (nonfacility) setting. The professional fees accounted for a minority of overall costs; in contrast, medication costs accounted for 82% of the total costs for the aflibercept monotherapy and 73% in the bevacizumab-first group at 2 years. Our model predicted an additional 15% lifetime cumulative savings if patients still not meeting the threshold criteria after switching to aflibercept were placed back on bevacizumab, and a similar degree of improvement if those on not meeting threshold criteria on aflibercept monotherapy were switched to bevacizumab. CONCLUSIONS: Medication is the dominant driver of the total expenses associated with the treatment of diabetic macular edema. Although cost savings are realized with bevacizumab-first step therapy, the magnitude was not as much as might be intuited, probably because of the high (70%) incidence of patients switching to aflibercept within protocol AC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Early-switch versus late-switch in patients with diabetic macular edema: a cost-effectiveness study.

BACKGROUND: To evaluate the cost-effectiveness of early- versus late-switch to the intravitreal-dexamethasone implant (DEX-i) in patients with diabetic macular edema (DME) who did not adequately respond to vascular endothelial growth factor inhibitors (anti-VEGF). METHODS: Retrospective analysis of a multicenter Clinical Data Registry. The registry included DME eyes who received 3 intravitreal anti-VEGF injections (early-switch) or > 3 intravitreal anti-VEGF injections (late-switch) before switching to DEX-i injections. The primary outcome was to estimate the incremental cost needed to obtain a best-corrected visual acuity (BCVA) improvement ≥ 0.1 or a central-retinal thickness CRT ≤ 250 µm. RESULTS: The analysis included 108 eyes, 32 (29.6%) and 76 (70.4%) in the early- and late-switch groups, respectively. Early-switch strategy was associated with a cost saving of €3,057.8; 95% CI: €2,406.4-3,928.4, p < 0.0001). Regarding incremental-cost-effectiveness ratio, late-switch group was associated with an incremental cost of €25,735.2 and €13,533.2 for achieving a BCVA improvement ≥ 0.1 at month 12 and at any of the time-point measured, respectively. At month 12, 38 (35.2%) eyes achieved a BCVA improvement ≥ 0.1. At month 12, 52 (48.1) eyes had achieved a CRT ≤ 250 micron. As compared to baseline, the mean (95% CI) CRT reduction was - 163.1 (- 212.5 to - 113.7) µm and - 161.6 (- 183.8 to - 139.3) µm in the early-switch and late-switch groups, respectively, p = 0.9463. CONCLUSIONS: In DME eyes, who did not adequately respond to anti-VEGF, switching to DEX-i at early stages (after the first 3-monthly injections) was found to be more cost-effective than extending the treatment to 6-monthly injections of anti-VEGF.

Assessment for Macular Thickness after Uncomplicated Phacoemulsification Using Optical Coherence Tomography.

PURPOSE: Macular edema including cystoid macular edema is one of the main causes of unfavorable visual outcomes after cataract surgery. The macular thickness and the occurrence of macular edema after uncomplicated cataract surgery was evaluated using optical coherence tomography (OCT) in this study. METHODS: Macular map images were taken by OCT before surgery and at 1 week, 1 month, and 2 months postsurgery. The subjects were classified into two groups (group 1, patients with no macular edema; group 2, patients with macular edema). Group 2 was defined as increase in central macular thickness (CMT) by 30% compared with that before surgery. The risk factors for macular edema were evaluated. Group 2 was divided into two subgroups: subclinical macular edema (group 2A) and cystoid macular edema (group 2B) and they were assessed in terms of the clinical course of best-corrected visual acuity and CMT. RESULTS: A total of 376 patients were enrolled in this study, of which 36 (9.57%, group 2) showed macular edema measured by OCT after the surgery. Univariate analysis for group 1 and 2 revealed that intracameral injection of epinephrine during phacoemulsification was associated with the development of macular edema. In group 2, five patients (1.33%) developed cystoid macular edema. Statistically significant differences in the clinical course of CMT were observed at 2 months (201.2 ± 23.1, 250.0 ± 29.8, and 371.0 ± 160.3 in group 1, group 2A, and group 2B, respectively; p < 0.001) and 1 month postoperatively (198.5 ± 23.6, 237.8 ± 40.9, and 314.0 ± 104.5 in group 1, group 2A, and group 2B, respectively; p < 0.001). Group 2B required additional treatment and eventually achieved best-corrected visual acuity of >0.2 with CMT in the normal range. CONCLUSIONS: The intracameral injection of epinephrine may cause macular edema after uncomplicated cataract surgery. Examination of CMT using OCT is recommended for the early detection of macular edema.

Healthcare expenditure of intravitreal anti-vascular endothelial growth factor inhibitors compared with dexamethasone implant for diabetic macular oedema.

PURPOSE: The aim of this study was to estimate the 1-year costs associated with treating diabetic macular oedema (DME) patients using current intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics compared with the dexamethasone implant. METHODS: We conducted a descriptive cost-evaluation analysis using data from Oslo University Hospital and literature to compare three different intravitreal drugs for DME: bevacizumab, aflibercept and dexamethasone. Stratification of patients into 'Naive' or 'Switch' group was based on treatment history. We estimated the costs from healthcare and 'extended' healthcare perspectives. Sensitivity analysis evaluated the impact of various parameters. RESULTS: The average injections per patient per year for the Naive group (bevacizumab), Switch group (aflibercept) and dexamethasone were 9.5, 9.1 and 3.0 respectively. From a healthcare perspective, the 1-year costs for the Naive group were 15% lower (bevacizumab, €3619), and for the Switch group, 23% higher (aflibercept, €5226) compared with dexamethasone (€4252). The 'extended' healthcare perspective showed the cost per patient per year for bevacizumab remained nominally lower in the Naive group, while dexamethasone remained lower for the Switch group (€5116 for dexamethasone, compared to €4987 for bevacizumab and €6537 for aflibercept). CONCLUSIONS: From a primary healthcare perspective, the dexamethasone as a first-line DME treatment may increase economic costs in settings where bevacizumab is used off-label. Treating resistant DMEwith dexamethasone may reduce the costs and treatment burden compared with switching to aflibercept.

Trends in Prevalence and Treatment of Diabetic Macular Edema and Vision-Threatening Diabetic Retinopathy Among Medicare Part B Fee-for-Service Beneficiaries.

IMPORTANCE: While diabetes prevalence among US adults has increased in recent decades, few studies document trends in diabetes-related eye disease. OBJECTIVE: To examine 10-year trends (2009-2018) in annual prevalence of Medicare beneficiaries with diabetes with a diagnosis of diabetic macular edema (DME) or vision-threatening diabetic retinopathy (VTDR) and trends in treatment. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study using Centers for Medicare & Medicaid Services research identifiable files, data for patients 65 years and older were analyzed from claims. Beneficiaries were continuously enrolled in Medicare Part B fee-for-service (FFS) insurance for the calendar year and had a diagnosis of diabetes on 1 or more inpatient claims or 2 or more outpatient claims during the calendar year or a 1-year look-back period. MAIN OUTCOMES AND MEASURES: Using diagnosis and procedure codes, annual prevalence was determined for beneficiaries with 1 or more claims for (1) any DME, (2) either DME or VTDR, and (3) anti-vascular endothelial growth factor (VEGF) injections, laser photocoagulation, or vitrectomy, stratified by any DME, VTDR with DME, and VTDR without DME. Racial and ethnic disparities in diagnosis and treatment are presented for 2018. RESULTS: In 2018, 6 960 823 beneficiaries (27.4%) had diabetes; half were aged 65 to 74 years (49.7%), half (52.7%) were women, and 75.7% were non-Hispanic White. From 2009 to 2018, there was an increase in the annual prevalence of beneficiaries with diabetes who had 1 or more claims for any DME (1.0% to 3.3%) and DME/VTDR (2.8% to 4.3%). Annual prevalence of anti-VEGF increased, particularly among patients with any DME (15.7% to 35.2%) or VTDR with DME (20.2% to 47.6%). Annual prevalence of laser photocoagulation decreased among those with any DME (45.5% to 12.5%), VTDR with DME (54.0% to 20.3%), and VTDR without DME (22.5% to 5.8%). Among all 3 groups, prevalence of vitrectomy in 2018 was less than half that in 2009. Prevalence of any DME and DME/VTDR was highest among Hispanic beneficiaries (5.0% and 7.0%, respectively) and Black beneficiaries (4.5% and 6.2%, respectively) and lowest among non-Hispanic White beneficiaries (3.0% and 3.8%, respectively). Among those with DME/VTDR, anti-VEGF was most prevalent among non-Hispanic White beneficiaries (30.3%). CONCLUSIONS AND RELEVANCE: From 2009 to 2018, prevalence of DME or VTDR increased among Medicare Part B FFS beneficiaries alongside an increase in anti-VEGF treatment and a decline in laser photocoagulation and vitrectomy.

Expression of Long Non-Coding RNA (lncRNA) SNHG5 in Patients with Refractory Diabetic Macular Edema and Its Regulatory Mechanism.

BACKGROUND The aim of this study was to assess use of lncRNAs as biomarkers in serum and aqueous humor of patients with diabetic macular edema (DME). MATERIAL AND METHODS Optical coherence tomography and fundus photography were used to analyze the retinal features of the patients. RT-qPCR was used to analyze the differential expression of lncRNA snhg5 in patients who have idiopathic macular hole (MH), DME, or refractory DME. The relationship between SNHG5 and the clinical characteristics of the patients was analyzed. The effect of SNHG5 on the hyperplasia and apoptosis of human retino-microvascular endothelial cells (HRMECs) and its mechanism were analyzed in vitro. RESULTS Patients with idiopathic MH developed retinal nerve epithelium rupture and retinal fundus thickening, and patients with DME or refractory DME showed significant macular edema with hemorrhaging. The refractory DME patients improved after treatment but still showed significant macular edema and multiple laser scarring. SNHG5 expression was not only low in the atrial fluid and plasma in DME patients, but also lower in the refractory DME group compared to the idiopathic MH patients. SNHG5 expression in the aqueous humor and plasma was negatively correlated with disease duration, body mass index, and levels of fasting blood glucose, glycated hemoglobin, proteinuria, and glycosuria. In the in vitro experiments, SNHG5 expression was significantly downregulated in high glucose-induced HMECs. After SNHG5 overexpression, cell proliferation, angiogenesis, and VEGF-A protein levels were distinctly downregulated. CONCLUSIONS SNHG5 correlates with the development of DME and is a potential target for therapy.

A Cost-Effectiveness Analysis of Intravitreal Aflibercept for the Prevention of Progressive Diabetic Retinopathy.

PURPOSE: To calculate costs required to prevent center-involved diabetic macular edema (CI-DME) or proliferative diabetic retinopathy (PDR), and to improve the diabetic retinopathy severity score (DRSS) with intravitreal anti-VEGF injections, as reported for aflibercept in 2 randomized control trials. DESIGN: Cost-effectiveness analysis modeling based on published data. SUBJECTS: None. METHODS: Results from PANORAMA and the Diabetic Retinopathy Clinical Research Network Protocol W were analyzed. Parameters collected included DRSS, risk reduction of PDR, risk reduction of CI-DME, and the number of treatments required. Costs were modeled based on 2020 Medicare reimbursement data practice settings of hospital-based facility and nonfacility. MAIN OUTCOME MEASURES: Cost to prevent cases of PDR and CI-DME and to improve DRSS stage. RESULTS: Over 2 years in Protocol W, the cost required to prevent 1 case of PDR was $83 000 ($72 400) in the facility (nonfacility) setting; in PANORAMA, the corresponding 2-year costs were $89 400 ($75 000) for the 2-mg aflibercept every 16 weeks (2Q16) arm, and $91 200 ($89 900) for the 2-mg aflibercept every 8 weeks as needed (2Q8PRN) arm. To prevent 1 case of CI-DME with vision loss in Protocol W, the cost was $154 000 ($133 000). For all CI-DME, with and without vision loss, in PANORAMA, the costs to prevent a case were $70 900 ($59 500) for the 2Q16 arm and $90 000 ($88 800) for the 2Q8PRN arm. In Protocol W, the overall accumulated total for cost/DRSS unit change at the 2-year point for facility (nonfacility) setting was $2700 ($2400)/DRSS. In the first year alone, it was $2100 ($1800)/DRSS and in the second year, it was $6100 ($5300)/DRSS. CONCLUSIONS: There is a considerable cost associated with the prevention of PDR and CI-DME with intravitreal aflibercept injections. A price per unit of change in DRSS is a new parameter that might serve as a benchmark in future utility analyses that could be used to bring the perspective to cost-utility considerations.

Surveillance of people with previously successfully treated diabetic macular oedema and proliferative diabetic retinopathy by trained ophthalmic graders: cost analysis from the EMERALD study.

BACKGROUND/AIMS: Surveillance of people with previously successfully treated diabetic macular oedema (DMO) and proliferative diabetic retinopathy (PDR) adds pressure on ophthalmology services. This study evaluated a new surveillance pathway entailing multimodal imaging reviewed by trained ophthalmic graders and compared it with the current standard care (face-to-face evaluation by an ophthalmologist). METHODS: Cost analysis of the new ophthalmic grader pathway, compared with the standard of care, from the perspective of the UK National Health Service, based on evidence from the Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy study. Resource use data were prospectively obtained including times to undertake each procedure. Effectiveness was assessed in terms of sensitivity and specificity of referral decisions in the grader pathway. Costs (SDs) were analysed per 100 patients separately for DMO and PDR at 2018/2019 costs. RESULTS: For DMO, where sensitivity was very high (97%), the cost difference (savings) for the grader's pathway would be £1390 per 100 patients. For PDR, the cost would be reduced by £461 for seven-field Early Treatment for Diabetic Retinopathy Study (ETDRS) images and by £1889 for ultrawide field images, per 100 patients. Ultrawide images required less time to be obtained and read than seven-field ETDRS. The real savings would be in ophthalmologist time, which could be then redirected to the evaluation of people at high risk of visual loss. CONCLUSIONS: Surveillance of people with previously successfully treated DMO and PDR by trained ophthalmic graders can achieve satisfactory results and release ophthalmologist time. TRIAL REGISTRATION NUMBERS: NCT03490318, ISRCTN10856638.

Racial, Ethnic, and Insurance-Based Disparities Upon Initiation of Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema in the US.

PURPOSE: 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). DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: 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). METHODS: Multivariate regression analyses were conducted to understand how race, ethnicity, insurance status, and geographic location were associated with baseline features. MAIN OUTCOME MEASURES: Visual acuity and DR severity. RESULTS: 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 P < 0.01). White and non-Hispanic patients presented with better VA compared with their counterparts (median of 0.68 and 2.53 greater ETDRS letters, respectively; P < 0.01). 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; P < 0.01). CONCLUSIONS: 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.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY ASSESSMENT OF THE DIABETIC MACULA: A Comparison Study Among Different Algorithms.

PURPOSE: To assess the impact of histogram adjustments and binarization thresholding selection on quantitative measurements of diabetic macular ischemia using optical coherence tomography angiography (OCTA). METHODS: Patients with diabetic retinopathy (DR) who had swept-source OCTA imaging obtained were enrolled. An additional group of 15 healthy control subjects was included for comparison. Previously used brightness/contrast changes and binarization thresholds were applied to original OCTA images to obtain and compare different binarized images. Qualitative and quantitative comparisons were performed. RESULTS: Thirty patients with DR (30 eyes) were included in the analysis. Fifteen eyes displayed the presence of diabetic macular edema. Qualitative grading revealed that binarized images obtained using a global threshold had better quality compared with local or multistep thresholds. The "median" filter was most frequently graded as the histogram adjustment resulting in binarized images with best quality. In the quantitative analysis, local thresholds tended to generate higher values of measured metrics. Differences in OCTA metrics between global and local thresholds were associated with presence of diabetic macular edema and signal strength index value. In the comparison between healthy and DR eyes, differences in OCTA metrics were significantly affected by binarization threshold selection. CONCLUSION: Quantitative OCTA parameters may be significantly influenced by strategies to quantify macular perfusion. Image quality and presence of macular edema can significantly impact OCTA-derived quantitative vascular measurements and differences between global and local binarization thresholds. These findings highlight the importance of consistent strategies to reliably generate quantitative OCTA metrics in patients with DR.

Self-examination low-cost full-field OCT (SELFF-OCT) for patients with various macular diseases.

PURPOSE: The treatment guidelines for many macular diseases rely on frequent monitoring with optical coherence tomography (OCT). However, the burden of frequent disease control leads to low therapy adherence in real life. OCT home monitoring would address this issue but requires an inexpensive and self-operable device. With self-examination low-cost full-field OCT (SELFF-OCT), our group has introduced a novel technology that may fulfill both requirements. In this pilot study, we report the initial experiences with a clinical prototype. METHODS: Fifty-one patients with different macular diseases were recruited in a cross-sectional study. The most common diseases were age-related macular degeneration (AMD; 39/51), diabetic macular edema (DME; 6/51), and retinal vein occlusion (RVO; 3/51). Patients received a short training in device usage and then performed multiple self-scans with the SELFF-OCT device. For comparison, scans with a standard clinical spectral domain (SD-)OCT were taken. RESULTS: After a brief training, 77% of the patients were able to successfully acquire images that were clinically gradable. No significant influence on success could be found for age (p = 0.08) or BCVA (p = 0.97). Relevant disease biomarkers in the most common retinal diseases could be detected. CONCLUSIONS: SELFF-OCT was used successfully for retinal self-examination and in the future could be used for retinal home monitoring. Future improvements in technology are expected to improve success rates and image quality. TRIAL REGISTRATION: The Trial was registered in the German Trial Register under the number DRKS00013755 on 14.03.2018.

Evaluation of a New Model of Care for People with Complications of Diabetic Retinopathy: The EMERALD Study.

PURPOSE: The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient's evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR. DESIGN: Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom. PARTICIPANTS: Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease. METHODS: A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists). MAIN OUTCOME MEASURES: Primary outcome: sensitivity of the new pathway. SECONDARY OUTCOMES: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings. RESULTS: The new pathway showed sensitivity of 97% (95% confidence interval [CI], 92%-99%) and specificity of 31% (95% CI, 23%-40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% [95% CI, 77%-91%] and 48% [95% CI, 41%-56%], respectively) or UWF images (83% [95% CI, 75%-89%] and 54% [95% CI, 46%-61%], respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% [95% CI, 78%-93%] and 49% [95% CI, 42%-56%], respectively, for UWF versus 80% [95% CI, 69-88%] and 40% [95% CI, 34%-47%], respectively, for 7-field ETDRS images). Participants preferred ophthalmologists' assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits. CONCLUSIONS: The new pathway has acceptable sensitivity and would release resources. Users' suggestions should guide implementation.

ASSESSMENT OF HYPERREFLECTIVE FOCI AFTER BEVACIZUMAB OR DEXAMETHASONE TREATMENT ACCORDING TO DURATION OF MACULAR EDEMA IN PATIENTS WITH BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To evaluate the association between hyperreflective foci (HRF) on spectral domain optical coherence tomography and therapeutic effect of intravitreal bevacizumab (IVB) or intravitreal dexamethasone implants (IVD) according to macular edema (ME) duration in branch retinal vein occlusion. METHODS: Consecutive treatment-naive patients received IVB or IVD for at least 6 months. Each group was subdivided according to ME duration (<3 months vs. ≥3 months). Hyperreflective foci and best-corrected visual acuity were compared. RESULTS: Of 139 eyes (139 patients), 69 received IVB and 70 received IVD. At baseline, eyes with ME ≥ 3 months had more outer and total retinal HRF than eyes with ME < 3 months (P < 0.001 and P = 0.001). At 6 months, the IVD group exhibited a greater reduction in outer retinal HRF than the IVB group in both ME duration subgroups (P = 0.015 and P < 0.001). In the ME ≥ 3 months group, IVD resulted in greater best-corrected visual acuity improvement than IVB (P = 0.017). CONCLUSION: Increased outer retinal HRF at baseline in eyes with ME ≥ 3 months together with a greater reduction in HRF at 6 months and better visual outcomes after IVD suggests that the inflammatory aspect of disease should be considered in the treatment of ME. Thus, IVD injection could be more appropriate for patients with a longer ME duration after branch retinal vein occlusion.

Aqueous Cytokine Expression and Higher Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study.

PURPOSE: To identify biomarkers for predicting response to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and optical coherence tomography (OCT) phenotype. DESIGN: The IMAGINE is a post hoc image analysis and cytokine expression assessment of the Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE) randomized clinical trial. METHODS: Subjects were categorized as anatomical responders or nonresponders, and within the responder group as rebounders and non-rebounders based on quantitative, longitudinal OCT criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines were measured at multiple timepoints. Expression was compared between responder groups and correlated with OCT imaging biomarkers. RESULTS: Of the 24 eyes studied, 79% were anatomical responders with 38% super responders, 17% early responders, and 25% slow responders. Twenty-one percent were nonresponders. Super responders had increased baseline vascular endothelial growth factor (VEGF) (880.0 pg/mL vs 245.4 pg/mL; P = .012) and decreased monocyte chemotactic protein-1 (MCP-1) (513.3 pg/mL vs 809.5 pg/mL; P = .0.042) concentrations compared with nonresponders. Interleukin-6 (-24.9 pg/mL vs 442.8 pg/mL; P = .032) concentrations increased among nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r = 0.49; P = .01). Panmacular retinal volume correlated with increased interleuckin-6 (r = 0.47; P = .02) and decreased MCP-1 (r = -0.45; P = .03). Matrix metallopeptidase-1 correlated with subretinal fluid volume (r = 0.50; P = .01). CONCLUSIONS: OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, which indicated a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.