Diabetic Eye Disease

Diabetic Eye Disease Publications

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.
Jacoba CMP, Celi LA, Silva PS. Biomarkers for Progression in Diabetic Retinopathy: Expanding Personalized Medicine through Integration of AI with Electronic Health Records. Semin Ophthalmol 2021;:1-8.Abstract
The goal of personalized diabetes eye care is to accurately predict in real-time the risk of diabetic retinopathy (DR) progression and visual loss. The use of electronic health records (EHR) provides a platform for artificial intelligence (AI) algorithms that predict DR progression to be incorporated into clinical decision-making. By implementing an algorithm on data points from each patient, their risk for retinopathy progression and visual loss can be modeled, allowing them to receive timely treatment. Data can guide algorithms to create models for disease and treatment that may pave the way for more personalized care. Currently, there exist numerous challenges that need to be addressed before reliably building and deploying AI algorithms, including issues with data quality, privacy, intellectual property, and informed consent.
Maturi RK, Glassman AR, Josic K, Antoszyk AN, Blodi BA, Jampol LM, Marcus DM, Martin DF, Melia M, Salehi-Had H, Stockdale CR, Punjabi OS, Sun JK, Sun JK. Effect of Intravitreous Anti-Vascular Endothelial Growth Factor vs Sham Treatment for Prevention of Vision-Threatening Complications of Diabetic Retinopathy: The Protocol W Randomized Clinical Trial. JAMA Ophthalmol 2021;Abstract
Importance: The role of anti-vascular endothelial growth factor injections for the management of nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) has not been clearly established. Objective: To determine the efficacy of intravitreous aflibercept injections compared with sham treatment in preventing potentially vision-threatening complications in eyes with moderate to severe NPDR. Design, Setting, and Participants: Data for this study were collected between January 15, 2016, and May 28, 2020, from the ongoing DRCR Retina Network Protocol W randomized clinical trial, conducted at 64 US and Canadian sites among 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study severity level, 43-53), without CI-DME. Analyses followed the intent-to-treat principle. Interventions: Eyes were randomly assigned to 2.0 mg of aflibercept injections (n = 200) or sham (n = 199) given at baseline; 1, 2, and 4 months; and every 4 months through 2 years. Between 2 and 4 years, treatment was deferred if the eye had mild NPDR or better. Aflibercept was administered in both groups if CI-DME with vision loss (≥10 letters at 1 visit or 5-9 letters at 2 consecutive visits) or high-risk proliferative diabetic retinopathy (PDR) developed. Main Outcomes and Measures: Development of CI-DME with vision loss or PDR through May 2020, when the last 2-year visit was completed. Results: Among the 328 participants (57.6% men [230 of 399 eyes]; mean [SD] age, 56 [11] years), the 2-year cumulative probability of developing CI-DME with vision loss or PDR was 16.3% with aflibercept vs 43.5% with sham. The overall hazard ratio for either outcome was 0.32 (97.5% CI, 0.21-0.50; P < .001), favoring aflibercept. The 2-year cumulative probability of developing PDR was 13.5% in the aflibercept group vs 33.2% in the sham group, and the 2-year cumulative probability of developing CI-DME with vision loss was 4.1% in the aflibercept group vs 14.8% in the sham group. The mean (SD) change in visual acuity from baseline to 2 years was -0.9 (5.8) letters with aflibercept and -2.0 (6.1) letters with sham (adjusted mean difference, 0.5 letters [97.5% CI, -1.0 to 1.9 letters]; P = .47). Conclusions and Relevance: In this randomized clinical trial, among eyes with moderate to severe NPDR, the proportion of eyes that developed PDR or vision-reducing CI-DME was lower with periodic aflibercept compared with sham treatment. However, through 2 years, preventive treatment did not confer visual acuity benefit compared with observation plus treatment with aflibercept only after development of PDR or vision-reducing CI-DME. The 4-year results will be important to assess longer-term visual acuity outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02634333.
Rageh A, Ashraf M, Fleming A, Silva PS. Automated Microaneurysm Counts on Ultrawide Field Color and Fluorescein Angiography Images. Semin Ophthalmol 2021;:1-7.Abstract
BACKGROUND: The severity and extent of microaneurysms (MAs) have been used to determine diabetic retinopathy (DR) severity and estimate the risk of DR progression over time. The recent introduction of ultrawide field (UWF) imaging has allowed ophthalmologists to readily image nearly the entire retina. Manual counting of MAs, especially on UWF images, is laborious and time-consuming, limiting its potential use in clinical settings. Automated MA counting techniques are potentially more accurate and reproducible compared to manual methods. METHOD: Review of available literature on current techniques of automated MA counting techniques on both ultrawide field (UWF) color images (CI) and fluorescein angiography (FA) images. RESULTS: Automated MA counting techniques on UWF images are still in the early phases of development with UWF-FA counts being further along. Early studies have demonstrated that these techniques are accurate and reproducible. CONCLUSION: Automated techniques may be an appropriate option for detecting and quantifying MAs on UWF images, especially in eyes with earlier DR severity. Larger studies are needed to appropriately validate these techniques and determine if they add substantially to clinical practice compared to standard DR grading.
Wang M, Garg I, Miller JB. Wide Field Swept Source Optical Coherence Tomography Angiography for the Evaluation of Proliferative Diabetic Retinopathy and Associated Lesions: A Review. Semin Ophthalmol 2021;:1-6.Abstract
Retinal imaging remains the mainstay for monitoring and grading diabetic retinopathy. The gold standard for detecting proliferative diabetic retinopathy (PDR) requiring treatment has long been the seven-field stereoscopic fundus photography and fluorescein angiography. In the past decade, ultra-wide field fluorescein angiography (UWF-FA) has become more commonly used in clinical practice for the evaluation of more advanced diabetic retinopathy. Since its invention, optical coherence tomography (OCT) has been an important tool for the assessment of diabetic macular edema; however, OCT offered little in the assessment of neovascular changes associated with PDR until OCT-A became available. More recently, swept source OCT allowed larger field of view scans to assess a variety of DR lesions with wide field swept source optical coherence tomography (WF-SS-OCTA). This paper reviews the role of WF-SS-OCTA in detecting neovascularization of the disc (NVD), and elsewhere (NVE), microaneurysms, changes of the foveal avascular zone (FAZ), intraretinal microvascular abnormalities (IRMA), and capillary non-perfusion, as well as limitations of this evolving technology.
Rodríguez-Valdés PJ, Rehak M, Zur D, Sala-Puigdollers A, Fraser-Bell S, Lupidi M, Chhablani J, Cebeci Z, Laíns I, Chaikitmongkol V, Fung AT, Okada M, Unterlauft JD, Smadar L, Loewenstein A, Iglicki M, Busch C. GRAding of functional and anatomical response to DExamethasone implant in patients with Diabetic Macular Edema: GRADE-DME Study. Sci Rep 2021;11(1):4738.Abstract
To analyze functional and anatomical response patterns to dexamethasone (DEX) implant in diabetic macular edema (DME), to describe proportion of responders and non-responders, and to propose a new DME grading system. Retrospective, multicenter, observational cohort study. Naïve and non-naïve DME patients were treated with DEX, with visual acuity (VA) ≥ 0.2 logMAR and central subfield thickness (CST) of ≥ 300 µm. Functional and anatomical responses were graded after 2 and 4 months, and categorized as early and stable improvement, early and progressive improvement, pendular response, delayed improvement, and persistent non-response. 417 eyes were included (175 treatment naïve eyes). Compared to non-naïve eyes, naïve eyes showed a very good functional response (VA gain ≥ 10 letters) more frequently after 2 and 4 months (56% and 57% [naïve] vs. 33% and 28% [non-naïve], p < 0.001). A VA gain < 5 letters (non-response) after 2 and 4 months was seen in 18% and 16% of naïve eyes, and in 49% and 53% of non-naïve eyes (p < 0.001). A lack of anatomical response was rare in both groups, but more frequently in non-naïve eyes (12% vs. 4%, p = 0.003). Functionally and anatomically, naïve eyes showed most frequently an early and stable improvement (functionally: 77/175 44%; anatomically: 123/175 eyes, 70%). Most non-naïve eyes experienced no significant improvement functionally (97/242 eyes, 40%), despite a mostly early and stable improvement anatomical response pattern (102/242 eyes, 42%). Functional but not anatomical response patterns were influenced by baseline VA. Naïve and non-naïve eyes show different functional and anatomical response patterns to DEX implant. Functional non-responders are rare in naïve eyes, whereas anatomical non-response is unusual in both groups.
Imamura M, Takahashi A, Matsunami M, Horikoshi M, Iwata M, Araki S-I, Toyoda M, Susarla G, Ahn J, Park KH, Kong J, Moon S, Sobrin L, Yamauchi T, Tobe K, Maegawa H, Kadowaki T, Maeda S. Genome-Wide Association Studies Identify Two Novel Loci Conferring Susceptibility to Diabetic Retinopathy in Japanese Patients with Type 2 Diabetes. Hum Mol Genet 2021;Abstract
Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases, and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (p < 1.0 × 10-4) in an independent case-control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stage-1 and -2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, p = 1.62 × 10-9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11-1.23, and rs140508424 within PALM2 on chromosome 9, p = 4.19 × 10-8, OR = 1.61, 95% CI 1.36-1.91. However, the association of these two loci were not replicated in Korean, European, or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (p = 2.17 × 10-6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.
Antonetti DA, Silva PS, Stitt AW. Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat Rev Endocrinol 2021;17(4):195-206.Abstract
Diabetes mellitus has profound effects on multiple organ systems; however, the loss of vision caused by diabetic retinopathy might be one of the most impactful in a patient's life. The retina is a highly metabolically active tissue that requires a complex interaction of cells, spanning light sensing photoreceptors to neurons that transfer the electrochemical signal to the brain with support by glia and vascular tissue. Neuronal function depends on a complex inter-dependency of retinal cells that includes the formation of a blood-retinal barrier. This dynamic system is negatively affected by diabetes mellitus, which alters normal cell-cell interactions and leads to profound vascular abnormalities, loss of the blood-retinal barrier and impaired neuronal function. Understanding the normal cell signalling interactions and how they are altered by diabetes mellitus has already led to novel therapies that have improved visual outcomes in many patients. Research highlighted in this Review has led to a new understanding of retinal pathophysiology during diabetes mellitus and has uncovered potential new therapeutic avenues to treat this debilitating disease.
Fickweiler W, Wolfson EA, Paniagua SM, Yu MG, Adam A, Bahnam V, Sampani K, Wu I-H, Musen G, Aiello LP, Shah H, Sun JK, King GL. Association of Cognitive Function and Retinal Neural and Vascular Structure in Type 1 Diabetes. J Clin Endocrinol Metab 2021;106(4):1139-1149.Abstract
CONTEXT: Cognitive dysfunction is a growing and understudied public health issue in the aging type 1 diabetic population and is difficult and time-consuming to diagnose. Studies in long duration type 1 diabetes have reported the presence of proliferative diabetic retinopathy was associated with cognitive dysfunction. OBJECTIVE: This study assessed whether structural and vascular abnormalities of the retina, representing an extension of the central nervous system, are associated with cognitive impairment and other complications of type 1 diabetes. METHODS: An observational cross-sectional study of individuals with 50 or more years of type 1 diabetes (Joslin Medalist Study) was conducted at a university hospital in the United States. The study included 129 participants with complete cognitive testing. Validated cognitive testing measures included psychomotor speed, and immediate, and delayed memory. Optical coherence tomography (OCT) and OCT angiography (OCTA) were performed to obtain neural retinal layer thicknesses and vascular density for superficial (SCP) and deep retinal capillary plexus (DCP). Multivariable modeling was adjusted for potential confounders associated with outcomes in unadjusted analyses. RESULTS: Decreased vessel density of the SCP and DCP was associated with worse delayed memory (DCP: P = .002) and dominant hand psychomotor speed (SCP: P = .01). Thinning of the retinal outer nuclear layer was associated with worse psychomotor speed both in nondominant and dominant hands (P = .01 and P = .05, respectively). Outer plexiform layer thickness was associated with delayed memory (P = .04). CONCLUSION: These findings suggest that noninvasive retinal imaging using OCT and OCTA may assist in estimating the risks for cognitive dysfunction in people with type 1 diabetes.
Tomita Y, Cagnone G, Fu Z, Cakir B, Kotoda Y, Asakage M, Wakabayashi Y, Hellström A, Joyal J-S, Talukdar S, Smith LEH, Usui Y. Vitreous metabolomics profiling of proliferative diabetic retinopathy. Diabetologia 2021;64(1):70-82.Abstract
AIMS/HYPOTHESIS: Proliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR. METHODS: We analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration. RESULTS: We identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024). CONCLUSIONS/INTERPRETATION: These results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR. Graphical abstract.
Hainsworth DP, Gao X, Bebu I, Das A, Olmos de Koo L, Barkmeier AJ, Tamborlane W, Lachin JM, Aiello LP, and and of and Group DCCTF-up EDICR. Refractive Error and Retinopathy Outcomes in Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Ophthalmology 2021;128(4):554-560.Abstract
PURPOSE: To determine the relationship between refractive error and diabetic retinopathy (DR). DESIGN: Clinical trial. PARTICIPANTS: Type I diabetes individuals with serial refractive error and DR stage measurements over 30 years in the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study. METHODS: Stage of DR was measured every 6 months from standard fundus photographs, and refractive error was measured annually during the 6.5 years of DCCT; then, both were staggered every fourth year during EDIC with the full cohort measured at EDIC years 4 and 10. Outcomes of DR were 2- or 3-step progression, presence of proliferative DR (PDR), clinically significant macular edema (CSME), diabetic macular edema (DME), or ocular surgery. Myopia, emmetropia, and hyperopia were defined as a spherical equivalent of ≤-0.5, >-0.5 and <0.5, and ≥0.5, respectively. MAIN OUTCOME MEASURES: For each outcome separately, Cox proportional hazard (PH) models assessed the association between the refractive error status and the subsequent risk of that outcome, both without and with adjustment for potential risk factors. RESULTS: Hyperopia was associated with a higher risk of 2-step progression (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.05-1.59), 3-step progression (HR, 1.35; 95% CI, 1.05-1.73), and PDR (HR, 1.40; 95% CI, 1.02-1.92) compared with emmetropia in unadjusted models. These associations remained significant after adjustment for DCCT treatment group, cohort, age, sex, smoking, duration of diabetes, systolic and diastolic blood pressures, pulse, low-density lipoprotein, high-density lipoprotein, triglycerides, albumin excretion rate, and DCCT/EDIC mean updated hemoglobin A1c (HbA1c) (2-step progression: HR, 1.28; 95% CI, 1.03-1.58; 3-step progression: HR, 1.30; 95% CI, 1.00-1.68; PDR: HR, 1.38; 95% CI, 1.00-1.90). Myopia was not associated with any of the 5 DR outcomes in the unadjusted models and only marginally associated with 2-step progression (HR, 1.11; 95% CI, 1.00-1.24) in the adjusted models. CONCLUSIONS: Myopia is not associated with DR progression risk. Hyperopia is an independent risk factor for 2-step and 3-step DR progression and PDR.
Azad AD, Chen EM, Hinkle J, Rayess N, Wu D, Eliott D, Mruthyunjaya P, Parikh R. Anti-Vascular Endothelial Growth Factor and Panretinal Photocoagulation Use after Protocol S for Proliferative Diabetic Retinopathy. Ophthalmol Retina 2021;5(2):151-159.Abstract
PURPOSE: To characterize the rates of panretinal photocoagulation (PRP) and anti-vascular endothelial growth factor (VEGF) medications before and after publication of the Diabetic Retinopathy Clinical Research Network protocol S. DESIGN: A retrospective, cross-sectional study from January 2012, through September 2019, using a nationally representative claims-based database, Clinformatics Data Mart Database (OptumInsight, Eden Prairie, MN). PARTICIPANTS: Eyes newly diagnosed with proliferative diabetic retinopathy (PDR), continuous enrollment, and no prior treatment with PRP or anti-VEGF agents. METHODS: Interrupted time series regression analysis was performed to identify the annual change in treatment rates before and after the publication of Protocol S (November 2015). MAIN OUTCOME MEASURES: Annual rates of anti-VEGF or PRP treatments per 1000 treated eyes with PDR. RESULTS: From 2012 through 2019, 10 035 PRP or anti-VEGF treatments were administered to 3685 PDR eyes. Of these, 63.6% (n = 6379) were anti-VEGF agents, and 36.4% (n = 3656) were PRP treatments. Throughout treatment, 88.7% of eyes treated with anti-VEGF received the same agent and 7.7% were treated with both PRP and anti-VEGF agents. Panretinal photocoagulation rates declined from 784/1000 treated eyes in 2012 to 566/1000 in 2019 (pre-Protocol S: β = -32 vs. post-Protocol S: -77; P = 0.005), whereas anti-VEGF rates increased from 876/1000 in 2012 to 1583/1000 in 2019 (β = -48 vs. 161, respectively; P = 0.001). Panretinal photocoagulation rates in diabetic macular edema (DME) eyes did not significantly differ from 474/1000 in 2012 to 363/1000 in 2019 (β = -9 vs. -58 respectively; P = 0.091), and anti-VEGF rates increased from 1533/1000 in 2012 to 2096/1000 in 2019 (β = -57 vs. 187; P = 0.043). In eyes without DME, PRP use declined from 1017/1000 in 2012 to 707/1000 in 2019 (β = -31 vs. -111, respectively; P < 0.001), and anti-VEGF use increased from 383/1000 in 2012 to 1226/1000 in 2019 (β = -48 vs. 140, respectively; P < 0.001). CONCLUSIONS: Following the publication of Protocol S, PRP rates decreased, while anti-VEGF rates increased. Panretinal photocoagulation rates did not significantly change among eyes with DME. Our findings indicate the impact that randomized controlled trials can have on real-world practice patterns.
Cui Y, Zhu Y, Wang JC, Lu Y, Zeng R, Katz R, Vingopoulos F, Le R, Laíns I, Wu DM, Eliott D, Vavvas DG, Husain D, Miller JW, Kim LA, Miller JB. Comparison of widefield swept-source optical coherence tomography angiography with ultra-widefield colour fundus photography and fluorescein angiography for detection of lesions in diabetic retinopathy. Br J Ophthalmol 2021;105(4):577-581.Abstract
AIMS: To compare widefield swept-source optical coherence tomography angiography (WF SS-OCTA) with ultra-widefield colour fundus photography (UWF CFP) and fluorescein angiography (UWF FA) for detecting diabetic retinopathy (DR) lesions. METHODS: This prospective, observational study was conducted at Massachusetts Eye and Ear from December 2018 to October 2019. Proliferative DR, non-proliferative DR and diabetic patients with no DR were included. All patients were imaged with a WF SS-OCTA using a Montage 15×15 mm scan. UWF CFP and UWF FA were taken by a 200°, single capture retinal imaging system. Images were independently evaluated for the presence or absence of DR lesions including microaneurysms (MAs), intraretinal microvascular abnormalities (IRMAs), neovascularisation elsewhere (NVE), neovascularisation of the optic disc (NVD) and non-perfusion areas (NPAs). All statistical analyses were performed using SPSS V.25.0. RESULTS: One hundred and fifty-two eyes of 101 participants were included in the study. When compared with UWF CFP, WF SS-OCTA was found to be superior in detecting IRMAs (p<0.001) and NVE/NVD (p=0.007). The detection rates of MAs, IRMAs, NVE/NVD and NPAs in WF SS-OCTA were comparable with UWF FA images (p>0.05). Furthermore, when we compared WF SS-OCTA plus UWF CFP with UWF FA, the detection rates of MAs, IRMAs, NVE/NVD and NPAs were identical (p>0.005). Agreement (κ=0.916) between OCTA and FA in classifying DR was excellent. CONCLUSION: WF SS-OCTA is useful for identification of DR lesions. WF SS-OCTA plus UWF CFP may offer a less invasive alternative to FA for DR diagnosis.
Antoszyk AN, Glassman AR, Beaulieu WT, Jampol LM, Jhaveri CD, Punjabi OS, Salehi-Had H, Wells JA, Maguire MG, Stockdale CR, Martin DF, Sun JK, Sun JK. Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA 2020;324(23):2383-2395.Abstract
Importance: Vitreous hemorrhage from proliferative diabetic retinopathy can cause loss of vision. The best management approach is unknown. Objective: To compare initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation for vitreous hemorrhage from proliferative diabetic retinopathy. Design, Setting, and Participants: Randomized clinical trial at 39 DRCR Retina Network sites in the US and Canada including 205 adults with vison loss due to vitreous hemorrhage from proliferative diabetic retinopathy who were enrolled from November 2016 to December 2017. The final follow-up visit was completed in January 2020. Interventions: Random assignment of eyes (1 per participant) to aflibercept (100 participants) or vitrectomy with panretinal photocoagulation (105 participants). Participants whose eyes were assigned to aflibercept initially received 4 monthly injections. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol criteria. Main Outcomes and Measures: The primary outcome was mean visual acuity letter score (range, 0-100; higher scores indicate better vision) over 24 weeks (area under the curve); the study was powered to detect a difference of 8 letters. Secondary outcomes included mean visual acuity at 4 weeks and 2 years. Results: Among 205 participants (205 eyes) who were randomized (mean [SD] age, 57 [11] years; 115 [56%] men; mean visual acuity letter score, 34.5 [Snellen equivalent, 20/200]), 95% (195 of 205) completed the 24-week visit and 90% (177 of 196, excluding 9 deaths) completed the 2-year visit. The mean visual acuity letter score over 24 weeks was 59.3 (Snellen equivalent, 20/63) (95% CI, 54.9 to 63.7) in the aflibercept group vs 63.0 (Snellen equivalent, 20/63) (95% CI, 58.6 to 67.3) in the vitrectomy group (adjusted difference, -5.0 [95% CI, -10.2 to 0.3], P = .06). Among 23 secondary outcomes, 15 showed no significant difference. The mean visual acuity letter score was 52.6 (Snellen equivalent, 20/100) in the aflibercept group vs 62.3 (Snellen equivalent, 20/63) in the vitrectomy group at 4 weeks (adjusted difference, -11.2 [95% CI, -18.5 to -3.9], P = .003) and 73.7 (Snellen equivalent, 20/40) vs 71.0 (Snellen equivalent, 20/40) at 2 years (adjusted difference, 2.7 [95% CI, -3.1 to 8.4], P = .36). Over 2 years, 33 eyes (33%) assigned to aflibercept received vitrectomy and 34 eyes (32%) assigned to vitrectomy received subsequent aflibercept. Conclusions and Relevance: Among participants whose eyes had vitreous hemorrhage from proliferative diabetic retinopathy, there was no statistically significant difference in the primary outcome of mean visual acuity letter score over 24 weeks following initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation. However, the study may have been underpowered, considering the range of the 95% CI, to detect a clinically important benefit in favor of initial vitrectomy with panretinal photocoagulation. Trial Registration: ClinicalTrials.gov Identifier: NCT02858076.

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