Diabetic Eye Disease

Ehlers JP, Yeh S, Maguire MG, Smith JR, Mruthyunjaya P, Jain N, Kim LA, Weng CY, Flaxel CJ, Schoenberger SD, Kim SJ. Intravitreal Pharmacotherapies for Diabetic Macular Edema: A Report by the American Academy of Ophthalmology. Ophthalmology 2022;129(1):88-99.Abstract
PURPOSE: To review the evidence on the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) and intravitreal corticosteroid pharmacotherapies for the treatment of diabetic macular edema (DME). METHODS: Literature searches were last conducted on May 13, 2020, in the PubMed database with no date restrictions and limited to articles published in English. The combined searches yielded 230 citations, of which 108 were reviewed in full text. Of these, 31 were deemed appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS: Only the 21 articles with level I evidence were included in this assessment. Seventeen articles provided level I evidence for 1 or more anti-VEGF pharmacotherapies, including ranibizumab (14), aflibercept (5), and bevacizumab (2) alone or in combination with other treatments for DME. Level I evidence was identified in 7 articles on intravitreal corticosteroid therapy for treatment of DME: triamcinolone (1), dexamethasone (4), and fluocinolone acetonide (2). CONCLUSIONS: Review of the available literature indicates that intravitreal injections of anti-VEGF agents and corticosteroids are efficacious treatments for DME. Elevated intraocular pressure and cataract progression are important potential complications of corticosteroid therapy. Further evidence is required to assess the comparative efficacy of these therapies. Given the limited high-quality comparative efficacy data, choice of therapy must be individualized for each patient and broad therapeutic access for patients is critical to maximize outcomes.
Sobrin L, Susarla G, Stanwyck L, Rouhana JM, Li A, Pollack S, Igo RP, Jensen RA, Li X, Ng MCY, Smith AV, Kuo JZ, Taylor KD, Freedman BI, Bowden DW, Penman A, Chen CJ, Craig JE, Adler SG, Chew EY, Cotch MF, Yaspan B, Mitchell P, Wang JJ, Klein BEK, Wong TY, Rotter JI, Burdon KP, Iyengar SK, Segrè AV. Gene Set Enrichment Analsyes Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy. Am J Ophthalmol 2022;233:111-123.Abstract
To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses applied to genome-wide association study meta-analyses. METHODS: We analyzed DR GWAS meta-analyses performed on 3246 Europeans and 2611 African Americans with type 2 diabetes. Gene sets relevant to 5 key DR pathophysiology processes were investigated: tissue injury, vascular events, metabolic events and glial dysregulation, neuronal dysfunction, and inflammation. Keywords relevant to these processes were queried in 4 pathway and ontology databases. Two GSEA methods, Meta-Analysis Gene set Enrichment of variaNT Associations (MAGENTA) and Multi-marker Analysis of GenoMic Annotation (MAGMA), were used. Gene sets were defined to be enriched for gene associations with DR if the P value corrected for multiple testing (Pcorr) was <.05. RESULTS: Five gene sets were significantly enriched for numerous modest genetic associations with DR in one method (MAGENTA or MAGMA) and also at least nominally significant (uncorrected P < .05) in the other method. These pathways were regulation of the lipid catabolic process (2-fold enrichment, Pcorr = .014); nitric oxide biosynthesis (1.92-fold enrichment, Pcorr = .022); lipid digestion, mobilization, and transport (1.6-fold enrichment, P = .032); apoptosis (1.53-fold enrichment, P = .041); and retinal ganglion cell degeneration (2-fold enrichment, Pcorr = .049). The interferon gamma (IFNG) gene, previously implicated in DR by protein-protein interactions in our GWAS, was among the top ranked genes in the nitric oxide pathway (best variant P = .0001). CONCLUSIONS: These GSEA indicate that variants in genes involved in oxidative stress, lipid transport and catabolism, and cell degeneration are enriched for genes associated with DR risk. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
Lu ES, Cui Y, Le R, Zhu Y, Wang JC, Laíns I, Katz R, Lu Y, Zeng R, Garg I, Wu DM, Eliott D, Vavvas DG, Husain D, Miller JW, Kim LA, Miller JB. Detection of neovascularisation in the vitreoretinal interface slab using widefield swept-source optical coherence tomography angiography in diabetic retinopathy. Br J Ophthalmol 2022;106(4):534-539.Abstract
AIMS: To compare the efficacy of diabetic retinal neovascularisation (NV) detection using the widefield swept-source optical coherence tomography angiography (WF SS-OCTA) vitreoretinal interface (VRI) Angio slab and SS-OCT VRI Structure slab. METHODS: A prospective, observational study was performed at Massachusetts Eye and Ear from January 2019 to June 2020. Patients with proliferative diabetic retinopathy (PDR), patients with non-proliferative diabetic retinopathy and patients with diabetes but without diabetic retinopathy were included. All patients were imaged with WF SS-OCTA using the 12×12 mm Angio scan protocol centred on the fovea and optic disc. The en-face SS-OCTA VRI Angio slab and SS-OCT VRI Structure slab were evaluated for the presence or absence of NV. SS-OCTA B-scan was used to classify NV according to cross-sectional morphology (forward, tabletop or flat). All statistical analyses were performed using SPSS V.26.0. RESULTS: One hundred and forty-two eyes of 89 participants were included in the study. VRI Angio detected NV at higher rates compared with VRI Structure (p<0.05). Combining VRI Angio and Structure improved detection rates compared with VRI Angio alone (p<0.05). Due to segmentation errors of the internal limiting membrane, NV with flat morphological classification had lower rates of detection on VRI Angio compared with NV with forward and tabletop morphology (p<0.05). CONCLUSIONS: WF SS-OCTA 12×12 mm VRI Angio and SS-OCT VRI Structure imaging centred on the fovea and optic disc detected NV with high sensitivity and low false positives. The VRI slab may be useful to diagnose and monitor PDR in clinical practice.
Sun JK, Josic K, Melia M, Glassman AR, Bailey C, Chalam KV, Chew EY, Cukras C, Grover S, Jaffe GJ, Lee R, Nielsen JS, Thompson DJS, Wiley HE, Ferris FL, Ferris FL. Conversion of Central Subfield Thickness Measurements of Diabetic Macular Edema Across Cirrus and Spectralis Optical Coherence Tomography Instruments. Transl Vis Sci Technol 2021;10(14):34.Abstract
Purpose: Develop equations to convert Cirrus central subfield thickness (CST) to Spectralis CST equivalents and vice versa in eyes with diabetic macular edema (DME). Methods: The DRCR Retina Network Protocol O data were split randomly to train (70% sample) and validate (30% sample) conversion equations. Data from an independent study (CADME) also validated the equations. Bland-Altman 95% limits of agreement between predicted and observed values evaluated the equations. Results: Protocol O included 374 CST scan pairs from 187 eyes (107 participants). The CADME study included 150 scan pairs of 37 eyes (37 participants). Proposed conversion equations are Spectralis = 40.78 + 0.95 × Cirrus and Cirrus = 1.82 + 0.94 × Spectralis regardless of age, sex, or CST. Predicted values were within 10% of observed values in 101 (90%) of Spectralis and 99 (88%) of Cirrus scans in the validation data; and in 136 (91%) of the Spectralis and 148 (99%) of the Cirrus scans in the CADME data. Adjusting for within-eye correlations, 95% of conversions are estimated to be within 17% (95% confidence interval, 14%-21%) of CST on Spectralis and within 22% (95% confidence interval, 18%-28%) of CST on Cirrus. Conclusions: Conversion equations developed in this study allow the harmonization of CST measurements for eyes with DME using a mix of current Cirrus and Spectralis device images. Translational Relevance: The CSTs measured on Cirrus and Spectralis devices are not directly comparable owing to outer boundary segmentation differences. Converting CST values across spectral domain optical coherence tomography instruments should benefit both clinical research and standard care efforts.
Fonda SJ, Bursell S-E, Lewis DG, Clary D, Shahon D, Silva PS. Prevalence of Diabetic Eye Diseases in American Indians and Alaska Natives (AI/AN) as Identified by the Indian Health Service's National Teleophthalmology Program Using Ultrawide Field Imaging (UWFI). Ophthalmic Epidemiol 2021;:1-9.Abstract
PURPOSE: Estimates of diabetic eye disease in American Indian and Alaska Natives (AI/AN) vary over time, region, and methods. This article reports recent prevalence of diabetic retinopathy (DR) and diabetic macular edema (DME) in AI/AN served by the Indian Health Services' (IHS) teleophthalmology program, as identified using ultrawide field imaging (UWFI). METHODS: This was a retrospective analysis of 2016-2019 clinical data (n = 53,900). UWF images were acquired by certified imagers using a validated protocol, and graded by licensed, certified optometrists supervised by an ophthalmologist. Graders evaluated the extent/severity of retinal lesions in comparison to standard photographs. DR lesions predominantly in any peripheral field were considered "predominantly peripheral lesions" (PPL). The analyses calculated prevalence of any DR, any DME, DR and DME severity, sight-threatening disease, and PPL. RESULTS: Patients averaged 56 years of age with a 68 mmol/mol A1c and 55% had had diabetes for 5+ years. Prevalence of any DR, any DME, and sight-threatening disease was 28.6%, 3.0%, and 3.0%. In patients with mild nonproliferative DR, PPL was seen in 25.3%. PPL suggested a more severe level of DR in 8.7% of patients. DR increased with age. DME decreased with age. Males and patients in the Nashville IHS area had more diabetic eye disease. CONCLUSION: AI/AN have a high burden of diabetes and its complications. The IHS is resource-constrained, making accurate disease estimates necessary for resource allocation and budget justifications to Congress. These data update the estimates of diabetic eye disease in Indian Country and suggest that UWFI identifies early DR.
Maguire MG, Liu D, Bressler SB, Friedman SM, Melia M, Stockdale CR, Glassman AR, Sun JK, Sun JK. Lapses in Care Among Patients Assigned to Ranibizumab for Proliferative Diabetic Retinopathy: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Ophthalmol 2021;139(12):1266-1273.Abstract
Importance: The follow-up schedule for individuals with eyes treated with anti-vascular endothelial growth factor agents for proliferative diabetic retinopathy (PDR) requires that patients return frequently for monitoring and repeated treatment. The likelihood that a patient will comply should be a consideration in choosing a treatment approach. Objective: To describe completion of scheduled examinations among participants assigned to intravitreous injections of ranibizumab for PDR in a multicenter randomized clinical trial. Design, Setting, and Participants: This post hoc analysis evaluates data from a randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012. Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. Data were analyzed from April 2019 to July 2021. Interventions: Ranibizumab injections for PDR or macular edema. Main Outcomes and Measures: A long lapse in care of 8 or more weeks past a scheduled examination, dropout from follow-up, visual acuity at 5 years. Results: Among 170 participants, the median age was 51 years, and 44.7% were female. Through 5 years of follow-up, 94 of 170 participants (55.3%) had 1 or more long lapse in care. Median time to the first long lapse was 210 weeks, and 69 of 94 participants (73.4%) returned for examination after the first long lapse. Fifty of 170 participants (29.4%) dropped out of follow-up by 5 years. Among the 120 participants who completed the 5-year examination, median change from baseline in visual acuity was -2 letters for participants who had 1 or more long lapse compared with +5 letters for those without a long lapse (P = .02). After multivariable adjustment, the odds ratio (95% CI) for baseline associations with 1 or more long lapse was 1.21 (1.03-1.43) for each 5-letter decrement in visual acuity score, 2.19 (1.09-4.38) for neovascularization of the disc and elsewhere, and 3.48 (1.38-8.78) for no prior laser treatment for diabetic macular edema. Conclusions and Relevance: Over 5 years, approximately half of the participants assigned to ranibizumab for PDR had a long lapse in care despite substantial effort by the DRCR Retina Network to facilitate timely completion of examinations. The likelihood of a long lapse in care during long-term follow-up needs to be considered when choosing treatment for PDR. Trial Registration: ClinicalTrials.gov Identifier: NCT01489189.
Cui Y, Zhu Y, Lu ES, Le R, Laíns I, Katz R, Wang JC, Garg I, Lu Y, Zeng R, Eliott D, Vavvas DG, Husain D, Miller JW, Kim LA, Wu DM, Miller JB. Widefield Swept-Source OCT Angiography Metrics Associated with the Development of Diabetic Vitreous Hemorrhage: A Prospective Study. Ophthalmology 2021;128(9):1312-1324.Abstract
PURPOSE: To investigate the association among widefield swept-source (SS) OCT angiography (OCTA) metrics and systemic parameters and vitreous hemorrhage (VH) occurrence in eyes with proliferative diabetic retinopathy (PDR). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-five eyes from 45 adults with PDR, with no history of VH, followed up for at least 3 months. METHODS: All patients underwent widefield SS OCTA (Montage 15 × 15 mm and high-definition (HD)-51 line scan) imaging. Images were evaluated independently by 2 graders for quantitative and qualitative widefield SS OCTA metrics defined a priori. Systemic and ocular parameters and widefield SS OCTA metrics were screened using least absolute shrinkage and selection operator and logistic or Cox regression for variable selection. Firth's bias-reduced logistic regression models (outcome, occurrence of VH) and Cox regression models (outcome, time to occurrence of VH) were used to identify parameters associated with VH occurrence. MAIN OUTCOME MEASURES: Occurrence of VH. RESULTS: Over a median follow-up of 363 days (range, 28-710 days), 13 of 55 PDR eyes (24%) demonstrated VH during the follow-up period. Presence of extensive neovascularizations (odds ratio, 8.05; 95% confidence interval [CI], 1.43-58.56; P = 0.02), defined as neovascularizations with total area of more than 4 disc diameters, and forward neovascularizations (odds ratio, 5.42; 95% CI, 1.26-35.16; P = 0.02) that traversed the posterior hyaloid face into the vitreous were associated with the occurrence of VH. The presence of flat neovascularizations (odds ratio, 0.25; 95% CI, 0.04-1.01; P = 0.05) confined to the posterior hyaloid face was associated with a lower risk of VH with borderline significance. Similarly, presence of extensive neovascularizations (hazard ratio, 18.24; 95% CI, 3.51-119.47; P < 0.001) and forward neovascularizations (hazard ratio, 9.60; 95% CI, 2.07-68.08; P = 0.002) was associated significantly with time to development of VH. CONCLUSIONS: Widefield SS OCTA is useful for evaluating neovascularizations and their relationship with the vitreous. The presence of forward and extensive neovascularizations was associated with the occurrence of VH in patients with PDR. Larger samples and longer follow-up are needed to verify the risk factors and imaging biomarkers for diabetic VH.
Li Y, Mitchell W, Elze T, Zebardast N. Association Between Diabetes, Diabetic Retinopathy, and Glaucoma. Curr Diab Rep 2021;21(10):38.Abstract
PURPOSE OF REVIEW: The strength of the relationship between diabetes, diabetic retinopathy (DR), and glaucoma remains controversial. We review evidence supporting and refuting this association and explore mechanistic pathological and treatment relationships linking these diseases. RECENT FINDINGS: While studies have shown diabetes/DR may increase the risk for glaucoma, this remains inconsistently demonstrated. Diabetes/DR may contribute toward glaucomatous optic neuropathy indirectly (either by increasing intraocular pressure or vasculopathy) or through direct damage to the optic nerve. However, certain elements of diabetes may slow glaucoma progression, and diabetic treatment may concurrently be beneficial in glaucoma management. Diabetes plays a significant role in poor outcomes after glaucoma surgery. While the relationship between diabetes/DR and glaucoma remains controversial, multiple mechanistic links connecting pathophysiology and management of diabetes, DR, and glaucoma have been made. However, a deeper understanding of the causes of disease association is needed.
Ashraf M, Rageh A, Gilbert M, Tolls D, Fleming A, Souka A, El-Baha S, Cavallerano JD, Sun JK, Aiello LP, Silva PS. Factors Affecting Predominantly Peripheral Lesion Identification and Grading. Transl Vis Sci Technol 2021;10(7):6.Abstract
Purpose: The purpose of this study was to determine factors affecting predominantly peripheral lesion (PPL) grading, such as qualitative versus quantitative assessment, device type, and severity of diabetic retinopathy (DR) in ultrawide field color images (UWF-CIs). Methods: Patients with DR had UWF-CI qualitatively graded for PPL using standardized techniques and had hemorrhages/microaneurysms (H/Mas) individually annotated for quantitative PPL grading on two different ultrawide field devices. Results: Among 791 eyes of 481 patients, 38.2% had mild nonproliferative DR (NPDR), 34.7% had moderate NPDR, and 27.1% had severe NPDR to proliferative DR (PDR). The overall agreement between qualitative and quantitative PPL grading was moderate (ĸ = 0.423, P < 0.001). Agreement rates were fair in eyes with mild NPDR (ĸ = 0.336, P < 0.001) but moderate in eyes with moderate NPDR (ĸ = 0.525, P < 0.001) and severe NPDR-PDR (ĸ = 0.409, P < 0.001). Increasing thresholds for quantitative PPL determination improved agreement rates, with peak agreements at H/Ma count differences of six for mild NPDR, five for moderate NPDR, and nine for severe NPDR-PDR. Based on ultrawide field device type (California = 412 eyes vs. 200Tx = 379 eyes), agreement between qualitative and quantitative PPL grading was moderate for all DR severities in both devices (ĸ = 0.369-0.526, P < 0.001) except for mild NPDR on the 200Tx, which had poor agreement (ĸ = 0.055, P = 0.478). Conclusions: Determination of PPL varies between standard qualitative and quantitative grading and is dependent on NPDR severity, device type, and magnitude of lesion differences used for quantitative assessment. Translational Relevance: Prior UWF studies have not accounted for imaging and grading factors that affect PPL, such factors need to be reviewed when assessing thresholds for DR progression rates.
Chen T, Jin L, Zhu W, Wang C, Zhang G, Wang X, Wang J, Yang K, Cochrane GM, Lamoureux EL, Friedman DS, Gilbert S, Lansingh VC, Resnikoff S, Zhao J, Xiao B, He M, Congdon N. Knowledge, attitudes and eye health-seeking behaviours in a population-based sample of people with diabetes in rural China. Br J Ophthalmol 2021;105(6):806-811.Abstract
AIMS: To assess knowledge of diabetes and acceptance of eye care among people with diabetes in rural China, to improve service uptake. METHODS: Population-based study of people in Guangdong, China, with glycosylated haemoglobin A1c≥6.5% and/or known history of diabetes. Between August and November 2014, participants answered a questionnaire (based on Delphi process/previous focus groups) on medical history, demographic characteristics, self-rated health and vision, knowledge about diabetes and diabetic retinopathy, quality of local healthcare, barriers to treatment, likely acceptance of eye exams and treatment, and interventions rated most likely to improve service uptake. Presenting visual acuity was assessed, fundus photography performed and images graded by trained graders. Potential predictors of accepting care were evaluated and confounders adjusted for using logistic regression. RESULTS: A total of 562 people (9.6% (256/5825), mean age 66.2±9.84 years, 207 (36.8%) men) had diabetes, 118 (22.3%) previously diagnosed. 'Very likely' or 'likely' acceptance of laser treatment (140/530=26.4%) was lower than for eye exams (317/530=59.8%, p<0.001). Predictors of accepting both exams and laser included younger age (p<.001) and prior awareness of diabetes diagnosis (p=0.004 and p=0.035, respectively). The leading barrier to receiving diabetes treatment was unawareness of diagnosis (409/454, 97.2%), while interventions rated most likely to improve acceptance of eye exams included reimbursement of travel costs (387/562, 73.0%), video or other health education (359/562, 67.7%) and phone call reminders (346/562, 65.3%). CONCLUSIONS: Improving diagnosis of diabetes, along with incentives, education and communication strategies, is most likely to enhance poor acceptance of diabetic eye care in this setting.
Chan CK, Mein CE, Glassman AR, Beaulieu WT, Calhoun CT, Jaffe GJ, Jampol LM, MacCumber MW, Maguire MG, Maturi RK, Salehi-Had H, Rofagha S, Sun JK, Martin DF, Martin DF. Pneumatic Vitreolysis with Perfluoropropane for Vitreomacular Traction with and without Macular Hole: DRCR Retina Network Protocols AG and AH. Ophthalmology 2021;128(11):1592-1603.Abstract
PURPOSE: To evaluate pneumatic vitreolysis (PVL) in eyes with vitreomacular traction (VMT) with and without full-thickness macular hole (FTMH). DESIGN: Two multicenter (28 sites) studies: a randomized clinical trial comparing PVL with observation (sham injection) for VMT without FTMH (Protocol AG) and a single-arm study assessing PVL for FTMH (Protocol AH). PARTICIPANTS: Participants were adults with central VMT (vitreomacular adhesion was ≤3000 μm). In Protocol AG, visual acuity (VA) was 20/32 to 20/400. In Protocol AH, eyes had a FTMH (≤250 μm at the narrowest point) and VA of 20/25 to 20/400. METHODS: Pneumatic vitreolysis using perfluoropropane (C3F8) gas. MAIN OUTCOME MEASURES: Central VMT release at 24 weeks (Protocol AG) and FTMH closure at 8 weeks (Protocol AH). RESULTS: From October 2018 through February 2020, 46 participants were enrolled in Protocol AG, and 35 were enrolled in Protocol AH. Higher than expected rates of retinal detachment and tear resulted in early termination of both protocols. Combining studies, 7 of 59 eyes (12% [95% CI, 6%-23%]; 2 eyes in Protocol AG, 5 eyes in Protocol AH) that received PVL developed rhegmatogenous retinal detachment (n = 6) or retinal tear (n = 1). At 24 weeks in Protocol AG, 18 of 23 eyes in the PVL group (78%) versus 2 of 22 eyes in the sham group (9%) achieved central VMT release without rescue vitrectomy (adjusted risk difference, 66% [95% CI, 44%-88%]; P< 0.001). The mean change in VA from baseline at 24 weeks was 6.7 letters in the PVL group and 6.1 letters in the sham group (adjusted difference, -0.8 [95% CI, -6.1 to 4.5]; P = 0.77). In Protocol AH, 10 of 35 eyes (29% [95% CI, 16%-45%]) achieved FTMH closure without rescue vitrectomy at 8 weeks. The mean change in VA from baseline at 8 weeks was -1.5 letters (95% CI, -10.3 to 7.3 letters). CONCLUSIONS: In most eyes with VMT, PVL induced hyaloid release. In eyes with FTMH, PVL resulted in hole closure in approximately one third of eyes. These studies were terminated early because of safety concerns related to retinal detachments and retinal tears.
Glassman AR, Beaulieu WT, Maguire MG, Antoszyk AN, Chow CC, Elman MJ, Jampol LM, Salehi-Had H, Sun JK, Sun JK. Visual Acuity, Vitreous Hemorrhage, and Other Ocular Outcomes After Vitrectomy vs Aflibercept for Vitreous Hemorrhage Due to Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol 2021;139(7):725-733.Abstract
Importance: Although there were no differences in mean visual acuity (VA) over 24 weeks after vitrectomy with panretinal photocoagulation (PRP) vs aflibercept in a randomized clinical trial among eyes with vitreous hemorrhage due to proliferative diabetic retinopathy (PDR), post hoc analyses may influence treatment choices. Objective: To compare exploratory outcomes between treatment groups that may affect treatment choices for patients with vitreous hemorrhage due to PDR. Design, Setting, and Participants: This post hoc analysis of a randomized clinical trial conducted at 39 DRCR Retina Network sites included adults with vision loss due to PDR-related vitreous hemorrhage for whom vitrectomy was considered. Data were collected from November 2016 to January 2020. Interventions: Random assignment to 4 monthly injections of aflibercept vs vitrectomy with PRP. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol-specific criteria. Main Outcomes and Measures: Visual acuity area under the curve (adjusted for baseline VA) and clearance of vitreous hemorrhage. Results: A total of 205 eyes were included in the analysis (115 male [56%] and 90 [44%] female participants; mean [SD] age, 57 [11] years). Among 89 eyes with a baseline VA of 20/32 to 20/160 (47 receiving aflibercept, including 4 [9%] that had undergone vitrectomy; 42 undergoing vitrectomy, including 3 [7%] that had received aflibercept), the adjusted mean difference in VA letter score over 24 weeks between the aflibercept and vitrectomy groups was -4.3 (95% CI, -10.6 to 1.9) compared with -16.7 (95% CI, -24.4 to -9.1) among 59 eyes with baseline VA worse than 20/800 (P = .02 for interaction; 26 in the aflibercept group, including 6 [23%] that had undergone vitrectomy; 33 in the vitrectomy group, including 8 [24%] that had received aflibercept). In the full cohort, the median time to clearance of the initial vitreous hemorrhage was 36 (interquartile range [IQR], 24-52) weeks in the aflibercept group vs 4 (IQR, 4-4) weeks in the vitrectomy group (difference, 32 [95% CI, 20-32] weeks; P < .001). Conclusions and Relevance: Both initial aflibercept and vitrectomy with PRP are viable treatment approaches for PDR-related vitreous hemorrhage. Although this study did not find a significant difference between groups in the primary outcome of mean VA over 24 weeks of follow-up, eyes receiving initial vitrectomy with PRP had faster recovery of vision over 24 weeks when baseline VA was worse than 20/800 and faster vitreous hemorrhage clearance. Approximately one-third of the eyes in each group received the alternative treatment (aflibercept or vitrectomy with PRP). These factors may influence treatment decisions for patients initiating therapy for PDR-related vitreous hemorrhage. Trial Registration: ClinicalTrials.gov Identifier: NCT02858076.
Hutton DW, Glassman AR, Stein JD, Bressler NM, Sun JK, Sun JK. Costs of Managing Diabetic Macular Edema with Good Visual Acuity with Aflibercept, Laser or Observation: DRCR Retina Network Protocol V. Am J Ophthalmol 2021;Abstract
PURPOSE: Since eyes with center-involved diabetic macular edema (CI-DME) and good baseline visual acuity (VA) showed no difference in VA loss when managed initially with observation, laser, or aflibercept, understanding the estimated costs of these strategies to the US population is relevant for health care planning. DESIGN: Pre-planned subgroup analysis from a randomized controlled trial METHODS, SETTING, AND PARTICIPANTS: Total costs for managing participants with CI-DME and good baseline VA assigned to aflibercept (n= 236), laser (n=240), or observation (n = 236) during the 2-year trial were calculated. Using epidemiological data and extrapolating costs, 10-year costs for caring for persons with CI-DME and good baseline VA throughout the US was estimated. INTERVENTIONS: Observation or laser groups initiated aflibercept if VA decreased. Aflibercept group received injections up to every 4 weeks. MAIN OUTCOMES AND MEASURES: Estimated 10-year U.S. population costs to manage CI-DME with good VA. RESULTS: Assuming all patients in the US with CI-DME and good baseline VA received aflibercept initially, 10-year costs were projected to be $28.80 billion compared with $14.42 billion if initially receiving laser treatment or $15.70 billion if initially observed, with aflibercept added if VA worsened in the laser or observation arms. CONCLUSIONS AND RELEVANCE: Similar VA outcomes on average are obtained by initially managing CI-DME and good baseline VA with laser or observation strategies instead of immediately using aflibercept. While any one of these three strategies might be warranted depending on an individual's specific circumstances, on a societal level, cost savings might be achieved with these first two approaches. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01909791.

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