Diabetic Eye Disease

Diabetic Eye Disease Publications

Hicks PM, Haaland B, Feehan M, Crandall AS, Pettey JH, Nuttall E, Self W, Hartnett ME, Bernstein P, Vitale A, Shakoor A, Shulman JP, Sieminski SF, Kim I, Owen LA, Murtaugh MA, Noyes A, Deangelis MM. Systemic Disease and Ocular Comorbidity Analysis of Geographically Isolated Federally Recognized American Indian Tribes of the Intermountain West. J Clin Med 2020;9(11)Abstract
BACKGROUND: The American Indian Navajo and Goshute peoples are underserved patient populations residing in the Four Corners area of the United States and Ibupah, Utah, respectively. METHODS: We conducted a cross-sectional study of epidemiological factors and lipid biomarkers that may be associated with type II diabetes, hypertension and retinal manifestations in tribal and non-tribal members in the study areas (n = 146 participants). We performed multivariate analyses to determine which, if any, risk factors were unique at the tribal level. Fundus photos and epidemiological data through standardized questionnaires were collected. Blood samples were collected to analyze lipid biomarkers. Univariate analyses were conducted and statistically significant factors at < 0.10 were entered into a multivariate regression. RESULTS: Of 51 participants for whom phenotyping was available, from the Four Corners region, 31 had type II diabetes (DM), 26 had hypertension and 6 had diabetic retinopathy (DR). Of the 64 participants from Ibupah with phenotyping available, 20 had diabetes, 19 had hypertension and 6 had DR. Navajo participants were less likely to have any type of retinopathy as compared to Goshute participants (odds ratio (OR) = 0.059; 95% confidence interval (CI) = 0.016-0.223; < 0.001). Associations were found between diabetes and hypertension in both populations. Older age was associated with hypertension in the Four Corners, and the Navajo that reside there on the reservation, but not within the Goshute and Ibupah populations. Combining both the Ibupah, Utah and Four Corners study populations, being American Indian ( = 0.022), residing in the Four Corners ( = 0.027) and having hypertension ( < 0.001) increased the risk of DM. DM ( < 0.001) and age ( = 0.002) were significantly associated with hypertension in both populations examined. When retinopathy was evaluated for both populations combined, hypertension ( = 0.037) and living in Ibupah ( < 0.001) were associated with greater risk of retinopathy. When combining both American Indian populations from the Four Corners and Ibupah, those with hypertension were more likely to have DM ( < 0.001). No lipid biomarkers were found to be significantly associated with any disease state. CONCLUSIONS: We found different comorbid factors with retinal disease outcome between the two tribes that reside within the Intermountain West. This is indicated by the association of tribe and with the type of retinopathy outcome when we combined the populations of American Indians. Overall, the Navajo peoples and the Four Corners had a higher prevalence of chronic disease that included diabetes and hypertension than the Goshutes and Ibupah. To the best of our knowledge, this is the first study to conduct an analysis for disease outcomes exclusively including the Navajo and Goshute tribe of the Intermountain West.
Ashraf M, Sampani K, Rageh A, Silva PS, Aiello LP, Sun JK. Interaction Between the Distribution of Diabetic Retinopathy Lesions and the Association of Optical Coherence Tomography Angiography Scans With Diabetic Retinopathy Severity. JAMA Ophthalmol 2020;Abstract
Importance: Studies have not yet determined whether the distribution of lesions in the retinal periphery alters the association between the severity of diabetic retinopathy (DR) and macular vessel density. Objective: To evaluate the association of DR lesion distribution with optical coherence tomography angiography (OCTA) metrics and DR severity. Design, Setting, and Participants: This cross-sectional observational study was conducted at a tertiary care center for diabetic eye disease among 225 patients with type 1 or 2 diabetes who had undergone imaging between February 15, 2016, and December 31, 2019. Exposures: Optical coherence tomography angiography 3 × 3-mm macular scans and ultra-widefield color imaging. Main Outcomes and Measures: Optical coherence tomography angiography vessel density in the superficial capillary plexus, intermediate capillary plexus, and deep capillary plexus and choriocapillaris flow density. The severity of DR and the predominantly peripheral lesions (PPL) were evaluated from ultra-widefield color imaging. Results: The study evaluated 352 eyes (225 patients; 125 men [55.6%]; mean [SD] age, 52.1 [15.1] years), of which 183 eyes (52.0%) had mild nonproliferative diabetic retinopathy (NPDR), 71 eyes (20.2%) had moderate NPDR, and 98 eyes (27.8%) had severe NPDR or proliferative diabetic retinopathy (PDR). In eyes with no PPL (209 [59.4%]), the mean (SD) vessel density in the superficial capillary plexus (mild NPDR, 38.1% [4.7%]; moderate NPDR, 36.4% [4.6%]; severe NPDR or PDR, 34.1% [4.1%]; P < .001) and the deep capillary plexus (mild NPDR, 45.8% [3.0%]; moderate NPDR, 45.8% [2.2%]; severe NPDR or PDR, 44.5% [1.9%]; P = .002), as well as the mean (SD) choriocapillaris flow density (mild NPDR, 69.7% [6.2%]; moderate NPDR, 67.6% [5.6%]; severe NPDR or PDR, 67.1% [5.6%]; P = .01), decreased with increasing DR severity. These associations remained statistically significant even after correcting for age, signal strength index, spherical equivalent, duration of diabetes, type of diabetes, and correlation between eyes of the same patient. In eyes with PPL (143 [40.6%]), mean (SD) vessel density in the superficial capillary plexus (mild NPDR, 34.1% [4.1%]; moderate NPDR, 35.2% [4.1%]; severe NPDR or PDR, 36.0% [4.3%]; P = .42) and the deep capillary plexus (mild NPDR, 44.5% [1.7%]; moderate NPDR, 45.4% [1.4%]; severe NPDR or PDR, 44.9% [1.5%]; P = .81), as well as the mean (SD) choriocapillaris flow density (mild NPDR, 67.1% [5.6%]; moderate NPDR, 69.3% [4.6%]; severe NPDR or PDR, 68.3% [5.6%]; P = .49), did not appear to change with increasing DR severity. Conclusions and Relevance: These results suggest that central retinal vessel density is associated with DR severity in eyes without, but not with, PPL. These findings suggest a potential need to stratify future optical coherence tomography angiography studies of eyes with DR by the presence or absence of PPL. If DR onset and worsening are associated with the location of retinal nonperfusion, assessment of global retinal nonperfusion using widefield angiography may improve the ability to evaluate DR severity and risk of DR worsening over time.
Tomita Y, Lee D, Tsubota K, Kurihara T. PPARα Agonist Oral Therapy in Diabetic Retinopathy. Biomedicines 2020;8(10)Abstract
Diabetic retinopathy (DR) is an eye condition that develops after chronically poorly-managed diabetes, and is presently the main cause for blindness on a global scale. Current treatments for DR such as laser photocoagulation, topical injection of corticosteroids, intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents and vitreoretinal surgery are only applicable at the late stages of DR and there are possibilities of significant adverse effects. Moreover, the forms of treatment available for DR are highly invasive to the eyes. Safer and more effective pharmacological treatments are required for DR treatment, in particular at an early stage. In this review, we cover recently investigated promising oral pharmacotherapies, the methods of which are safer, easier to use, patient-friendly and pain-free, in clinical studies. We especially focus on peroxisome proliferator-activator receptor alpha (PPARα) agonists in which experimental evidence suggests PPARα activation may be closely related to the attenuation of vascular damages, including lipid-induced toxicity, inflammation, an excess of free radical generation, endothelial dysfunction and angiogenesis. Furthermore, oral administration of selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) agonists may induce hepatic fibroblast growth factor 21 expression, indirectly resulting in retinal protection in animal studies. Our review will enable more comprehensive approaches for understanding protective roles of PPARα for the prevention of DR development.
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 2020;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.
Ashraf M, Shokrollahi S, Pisig AU, Sampani K, AbdelAl O, Cavallerano JD, Robertson G, Fleming A, van Hemert J, Pitoc CM, Sun JK, Aiello LP, Silva PS. Retinal vascular caliber association with nonperfusion and diabetic retinopathy severity depends on vascular caliber measurement location. Ophthalmol Retina 2020;Abstract
PURPOSE: To evaluate the association of retinal nonperfusion and diabetic retinopathy (DR) severity with location of vascular caliber measurement using ultrawide field (UWF) imaging. DESIGN: Retrospective image review SUBJECTS: Adult subjects with diabetes mellitus. METHODS: All images from subjects with same day UWF fluorescein angiography (FA) and color imaging (CI) were evaluated. DR severity and predominantly peripheral lesions (PPL) were graded from UWF-CI. Nonperfusion was quantified using UWF-FA in defined retinal regions [posterior pole (PP), mid-periphery (MP), far-periphery (FP)]. Retinal vessel calibers were measured at an inner and outer zone centered on the optic disc. MAIN OUTCOME MEASURES: Nonperfusion index (NPI) in the PP, MP and FP. Mean arteriole and venule diameter in the inner and outer zones. RESULTS: 285 eyes of 193 patients [(24.9% mild nonproliferative DR (NPDR), 22.8% moderate, 37.5% severe and 14.7% proliferative DR (PDR)] were reviewed. There were no significant associations between inner zone arteriolar diameter and retinal NPI overall or in any retinal region. In the outer zone, eyes with thinnest arteriolar calibers (Q1) were associated with a 1.7-2.4-fold increase in nonperfusion across all retinal regions compared to the remaining eyes [P=0.002 (PP) to 0.048 (FP)]. In the outer zone, the percentage of eyes in the thinnest quartile of retinal arteriolar diameter increased with worsening DR severity (10% in mild NPDR and 31% in PDR, p=0.007). This association was not observed when measured within the inner zone (p=0.129). All venular caliber associations were not statistically significant when corrected for potentially confounding factors. Thinner outer zone retinal arteriolar caliber (Q1) was more common in eyes with PPL compared to eyes without PPL (34.1% vs 20.8%, p=0.017) as were thicker outer venular calibers (Q4) (33% vs 21.3%, p=0.036). Presence of PPL was associated with thinner outer zone arteriolar caliber (109.7±26.5 vs 123.0±29.5, p=0.001). CONCLUSIONS: The association of vascular caliber with nonperfusion and DR severity differs based upon the retinal location at which vascular caliber is measured. Peripheral arterial narrowing is associated with increasing nonperfusion, worsening DR severity and presence of PPL. In contrast, inner zone retinal arteriolar caliber is not associated with these findings.
, Hainsworth DP, Gao X, Bebu I, Das A, Olmos de Koo L, Barkmeier AJ, Tamborlane W, Lachin JM, Aiello LP, Aiello LP. Refractive Error and Retinopathy Outcomes in Type 1 Diabetes: the DCCT/EDIC Study. Ophthalmology 2020;Abstract
OBJECTIVE: Determine relationship between refractive error and diabetic retinopathy (DR). DESIGN: Clinical trial SUBJECTS: Myopia is a non-modifiable risk factor reportedly associated with less severe DR in small case series, but this association has not been confirmed in large prospective studies. With a large cohort of patients with type I diabetes followed over 30 years with serial refractive error and DR stage measurements, the Diabetes Control and Complications Trial and follow-up Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC) provide a unique opportunity to evaluate the association between refractive error and DR development and progression. METHODS: DR stage was measured every six 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. DR outcomes 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 hazards models assessed the association between refractive error status and the subsequent risk of that outcome, both without and with adjustment for potential risk factors. RESULTS: Hyperopia was associated with higher risk of 2-step progression (hazard ratio (HR)=1.29, 95%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 to 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 pressure, pulse, LDL, HDL, triglycerides, albumin excretion rate, and DCCT/EDIC mean updated 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 five 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.
Glassman AR, Wells JA, Josic K, Maguire MG, Antoszyk AN, Baker C, Beaulieu WT, Elman MJ, Jampol LM, Sun JK. Five-Year Outcomes after Initial Aflibercept, Bevacizumab, or Ranibizumab Treatment for Diabetic Macular Edema (Protocol T Extension Study). Ophthalmology 2020;127(9):1201-1210.Abstract
PURPOSE: Assess follow-up treatment and clinical outcomes at 5 years in eyes initially treated with anti-VEGF therapy for center-involved diabetic macular edema (CI-DME) in a 2-year randomized clinical trial. DESIGN: Multicenter cohort study. PARTICIPANTS: Participants with diabetic macular edema (DME) and visual acuity (VA) 20/32 to 20/320 enrolled in DRCR.net Protocol T with visits 5 years after randomization (3 years after Protocol T completion). METHODS: Participants were assigned randomly to aflibercept, bevacizumab, or ranibizumab with protocol-defined follow-up and re-treatment for 2 years. Thereafter, participants were managed at clinician discretion and recalled for a 5-year visit. MAIN OUTCOME MEASURES: Anti-vascular endothelial growth factor (VEGF) treatment, VA letter score, and central subfield thickness (CST). RESULTS: Sixty-eight percent (317/463) of eligible participants completed the 5-year visit. Between years 2 and 5, 68% (217/317) of study eyes received at least 1 anti-VEGF treatment (median, 4; interquartile range [IQR], 0-12). At 5 years, mean VA improved from baseline by 7.4 letters (95% confidence interval [CI], 5.9-9.0) but decreased by 4.7 letters (95% CI, 3.3-6.0) between 2 and 5 years. When baseline VA was 20/50 to 20/320, mean 5-year VA was 11.9 letters (95% CI, 9.3-14.5) better than baseline but 4.8 letters (95% CI, 2.5-7.0) worse than 2 years. When baseline VA was 20/32 to 20/40, mean 5-year VA was 3.2 letters (95% CI, 1.4-5.0) better than baseline but 4.6 letters (95% CI, 3.1-6.1) worse than 2 years. Mean CST decreased from baseline to 5 years by 154 μm (95% CI, 142-166) and was stable between 2 and 5 years (-1 μm; 95% CI, -12 to 9). CONCLUSIONS: Among the two-thirds of eligible Protocol T participants who completed a 5-year visit, mean VA improved from baseline to 5 years without protocol-defined treatment after follow-up ended at 2 years. Although mean retinal thickness was similar at 2 and 5 years, mean VA worsened during this period. Additional investigation into strategies to improve long-term outcomes in eyes with DME seems warranted to determine if VA can be better maintained with different management approaches.
Chen EM, Armstrong GW, Cox JT, Wu DM, Hoover DR, Del Priore LV, Parikh R. Association of the Affordable Care Act Medicaid Expansion with Dilated Eye Examinations among the United States Population with Diabetes. Ophthalmology 2020;127(7):920-928.Abstract
PURPOSE: To evaluate the association between Medicaid expansion and diabetic dilated eye examinations. DESIGN: A retrospective difference in differences (DiD) analysis using individual-level survey response data from January 1, 2009, to December 31, 2017. PARTICIPANTS: A total of 52 392 survey responses from 50 states and the District of Columbia between 2009 and 2017. Responders were adults aged 18 to 64 years reporting a previous diagnosis of diabetes and a household income below 138% of the US federal poverty line (FPL). METHODS: The Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System data were used to identify survey responders who were asked about the presence of dilated eye examinations from years before and after Medicaid expansion implementation. MAIN OUTCOME MEASURES: The DiD in proportion of dilated eye examinations among diabetic persons aged 18 to 64 years with household incomes below 138% of the FPL between states that did and did not implement Medicaid expansion. RESULTS: Implementation of Medicaid expansion policies was associated with a 1.3% (95% confidence interval [CI], -3.8 to 6.4; P = 0.61), 6.3% (95% CI, 1.3-11.3; P = 0.016), 4.1% (95% CI, -0.8 to 9.0; P = 0.11), and 2.3% (95% CI, -1.6 to 6.2; P = 0.23) increase in the proportion of diabetic persons aged 18 to 64 years with incomes below 138% of the FPL receiving a dilated eye examination within the past year due to Medicaid expansion 1, 2, 3, and 4 cumulative years after expansion, respectively. CONCLUSIONS: Medicaid expansion policies were significantly associated with an increase in dilated eye examination rates within the first 2 years after implementation. However, this increase did not persist beyond this period, with nonsignificant increases 3 and 4 cumulative years after implementation. Healthcare policymakers should be aware that additional measures beyond expanding insurance coverage may be necessary to increase and sustain the rate of dilated eye examinations among diabetic populations.
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 2020;Abstract
PURPOSE: To characterize the rates of pan-retinal laser photocoagulation (PRP) and anti-vascular endothelial growth factor (anti-VEGF) medications before and after publication of the DRCR.net Protocol S. DESIGN: A retrospective, cross-sectional study from January 1, 2012 to September 30, 2019 using a nationally representative claims-based database, Clinformatics™ Data Mart Database (OptumInsight, Eden Prairie, MN). Subjects, Participants, and/or Controls: Eyes newly diagnosed with proliferative diabetic retinopathy (PDR), continuous enrollment, and no prior treatment with PRP or anti-VEGF. Methods, Intervention, or Testing: Interrupted time series regression analysis was performed to identify the annual change in treatment rates before and after the publication of Protocol S (November 24, 2015). MAIN OUTCOME MEASURES: Annual rates of anti-VEGF or PRP treatments per 1,000 treated eyes with PDR. RESULTS: From 2012 to 2019, 10035 PRP or anti-VEGF treatments were given to 3685 PDR eyes. 63.6% (6379) of these were anti-VEGF agents and 36.4% (3656) were PRP treatments. 88.7% of eyes treated with anti-VEGF received the same agent throughout treatment and 7.7% were treated with both PRP and anti-VEGF agents. PRP rates declined from 784/1,000 treated eyes in 2012 to 566/1,000 in 2019 (pre-Protocol S: β = -32 vs. post-Protocol S: β = -77, p=0.005) while anti-VEGF rates increased from 876/1000 in 2012 to 1583/1000 in 2019 (β = -48 vs. β = 161, p=0.001). PRP rates in DME eyes did not significantly change from 474/1000 in 2012 to 363/1000 in 2019 (β = -9 vs. β = -58, p=0.091), but anti-VEGF rates increased significantly from 1533/1000 in 2012 to 2096/1000 in 2019 (β = -57 vs. β = 187, p=0.043). In eyes without DME, PRP use declined from 1017/1000 in 2012 to 707/1000 in 2019 (β = -31 vs. β = -111, p<0.001) and anti-VEGF use increased from 383/1000 in 2012 to 1226/1000 in 2019 (β = -48 vs. β = 140, p<0.001). CONCLUSIONS: Following the publication of Protocol S, PRP rates decreased while anti-VEGF rates increased largely from increases in bevacizumab use. PRP rates significantly declined among eyes without 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 2020;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.
Sadda SR, Nittala MG, Taweebanjongsin W, Verma A, Velaga SB, Alagorie AR, Sears CM, Silva PS, Aiello LP. Quantitative Assessment of the Severity of Diabetic Retinopathy. Am J Ophthalmol 2020;218:342-352.Abstract
PURPOSE: To determine whether a quantitative approach to assessment of the severity of diabetic retinopathy (DR) lesions on ultrawide field (UWF) images can provide new parameters to predict progression to proliferative diabetic retinopathy (PDR). METHODS: One hundred forty six eyes from 73 participants with DR and 4 years of follow-up data were included in this post hoc analysis, which was based on a cohort of 100 diabetic patients enrolled in a previously published prospective, comparative study of UWF imaging at the Joslin Diabetes Center. Diabetic Retinopathy Severity Score level was determined at baseline and 4-year follow-up visits using mydriatic 7-standard field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs. All individual DR lesions (hemorrhage [H], microaneurysm [ma], cotton wool spot [CWS], intraretinal microvascular abnormality [IRMA]) were manually segmented on stereographic projected UWF. For each lesion type, the frequency/number, surface area, and distances from the optic nerve head (ONH) were computed. These quantitative parameters were compared between eyes that progressed to PDR in 4 years and eyes that did not progress. Univariable and multivariable logistic regression analyses were performed to identify parameters that were associated with an increased risk for progression to PDR. RESULTS: A total of 146 eyes of 73 subjects were included in the final analysis. The mean age of the study cohort was 53.1 years, and 42 (56.8%) subjects were female. The number and surface area of H/ma's and CWSs were significantly (P ≤ .05) higher in eyes that progressed to PDR compared with eyes that did not progress by 4 years. Similarly, H/ma's and CWSs were located further away from the ONH (ie, more peripheral) in eyes that progressed (P < .05). DR lesion parameters that conferred a statistically significant increased risk for proliferative diabetic retinopathy in the multivariate model included hemorrhage area (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.25-5.53), and greater distance of hemorrhages from the ONH (OR, 1.24; 95% CI, 0.97-1.59). CONCLUSIONS: Quantitative analysis of DR lesions on UWF images identifies new risk parameters for progression to PDR including the surface area of hemorrhages and the distance of hemorrhages from the ONH. Although these risk factors will need to be confirmed in larger, prospective studies, they highlight the potential for quantitative lesion analysis to inform the design of a more precise and complete staging system for diabetic retinopathy severity in the future. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
Vujosevic S, Aldington SJ, Silva P, Hernández C, Scanlon P, Peto T, Simó R. Screening for diabetic retinopathy: new perspectives and challenges. Lancet Diabetes Endocrinol 2020;8(4):337-347.Abstract
Although the prevalence of all stages of diabetic retinopathy has been declining since 1980 in populations with improved diabetes control, the crude prevalence of visual impairment and blindness caused by diabetic retinopathy worldwide increased between 1990 and 2015, largely because of the increasing prevalence of type 2 diabetes, particularly in low-income and middle-income countries. Screening for diabetic retinopathy is essential to detect referable cases that need timely full ophthalmic examination and treatment to avoid permanent visual loss. In the past few years, personalised screening intervals that take into account several risk factors have been proposed, with good cost-effectiveness ratios. However, resources for nationwide screening programmes are scarce in many countries. New technologies, such as scanning confocal ophthalmology with ultrawide field imaging and handheld mobile devices, teleophthalmology for remote grading, and artificial intelligence for automated detection and classification of diabetic retinopathy, are changing screening strategies and improving cost-effectiveness. Additionally, emerging evidence suggests that retinal imaging could be useful for identifying individuals at risk of cardiovascular disease or cognitive impairment, which could expand the role of diabetic retinopathy screening beyond the prevention of sight-threatening disease.