Jerry D. Cavallerano

Stereo nonmydriatic digital-video color retinal imaging compared with Early Treatment Diabetic Retinopathy Study seven standard field 35-mm stereo color photos for determining level of diabetic retinopathy.

OBJECTIVE To evaluate the ability to determine clinical levels of diabetic retinopathy, timing of next appropriate retinal evaluation, and necessity of referral to ophthalmology specialists using stereoscopic nonmydriatic digital-video color retinal images as compared with Early Treatment Diabetic Retinopathy Study (ETDRS) seven standard field 35-mm stereoscopic color fundus photographs. DESIGN Prospective, clinic-based, comparative instrument validation study. PARTICIPANTS Fifty-four patients (108 eyes) with type 1 or type 2 diabetes mellitus selected after chart review from a single center to include the full spectrum of diabetic retinopathy. METHODS Nonsimultaneous 45 degrees -field stereoscopic digital-video color images (JVN images) were obtained from three fields with the Joslin Vision Network (JVN) system before pupil dilation. Following pupil dilation, ETDRS seven standard field 35-mm stereoscopic color 30 degrees fundus photographs (ETDRS photos) were obtained. Joslin Vision Network images and ETDRS photos were graded on a lesion-by-lesion basis by two independent, masked readers to assess ETDRS clinical level of diabetic retinopathy. An independent ophthalmology retina specialist adjudicated interreader disagreements in a masked fashion. MAIN OUTCOME MEASURES Determination of ETDRS clinical level of diabetic retinopathy, timing of next ophthalmic evaluation of diabetic retinopathy, and need for prompt referral to ophthalmology specialist. RESULTS There was substantial agreement (kappa = 0.65) between the clinical level of diabetic retinopathy assessed from the undilated JVN images and the dilated ETDRS photos. Agreement was excellent (kappa = 0.87) for suggested referral to ophthalmology specialists for eye examinations. Comparison of individual lesions between the JVN images and the ETDRS photos and for interreader comparisons were comparable to the prior ETDRS study. CONCLUSIONS Undilated digital-video images using the JVN system were comparable photographs for the determination of diabetic retinopathy level. The results validate the agreement between nonmydriatic JVN images and dilated ETDRS photographs and suggest that this digital technique may be an effective telemedicine tool for remotely determining the level of diabetic retinopathy, suggesting timing of next retinal evaluation and identifying the need for prompt referral to ophthalmology specialists. Thus, the JVN system would be an appropriate tool for facilitating increased access of diabetic patients into recommended eye evaluations, but should not be construed as a paradigm that would replace the need for comprehensive eye examinations.

Protection From Retinopathy and Other Complications in Patients With Type 1 Diabetes of Extreme Duration: The Joslin 50-Year Medalist Study

OBJECTIVE To assess complication prevalence and identify protective factors in patients with diabetes duration of ≥50 years. Characterization of a complication-free subgroup in this cohort would suggest that some individuals are protected from diabetes complications and allow identification of endogenous protective factors. RESEARCH DESIGN AND METHODS Cross-sectional, observational study of 351 U.S. residents who have survived with type 1 diabetes for ≥50 years (Medalists). Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA1c, lipids, and advanced glycation end products (AGEs). Retrospective chart review provided longitudinal ophthalmic data for a subgroup. RESULTS A high proportion of Medalists remain free from proliferative diabetic retinopathy (PDR) (42.6%), nephropathy (86.9%), neuropathy (39.4%), or cardiovascular disease (51.5%). Current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Subjects with high plasma carboxyethyl-lysine and pentosidine were 7.2-fold more likely to have any complication. Of Medalists without PDR, 96% with no retinopathy progression over the first 17 years of follow-up did not experience retinopathy worsening thereafter. CONCLUSIONS The Medalist population is likely enriched for protective factors against complications. These factors might prove useful to the general population with diabetes if they can be used to induce protection against long-term complications. Specific AGE combinations were strongly associated with complications, indicating a link between AGE formation or processing with development of diabetic vasculopathy.

Rapid and durable recovery of visual function in a patient with von hippel-lindau syndrome after systemic therapy with vascular endothelial growth factor receptor inhibitor su5416

PURPOSE To present a case of rapid and durable recovery of visual function in a patient with von Hippel-Lindau syndrome and optic nerve head hemangioblastoma after systemic treatment with the vascular endothelial growth factor (VEGF) receptor inhibitor SU5416. DESIGN Interventional case report. METHODS Visual function parameters, including visual acuity, automated visual field, and contrast sensitivity, were evaluated using standardized methods repeatedly over a 15-month period. Fundus photographs and fluorescein angiograms were also obtained. Central nervous system lesions were monitored by computed tomography (CT) and magnetic resonance imaging (MRI) scans. Treatment involved the systemic administration of the VEGF receptor inhibitor SU5416. MAIN OUTCOME MEASURES Clinical presentation, visual acuity using Early Treatment Diabetic Retinopathy Study protocol, Humphrey automated perimetry, (Zeiss Humphrey Systems, Dublin, CA) Vistech contrast sensitivity (Vistech Consultants Inc., Dayton, OH) Farnsworth (Farnsworth-Munsell Color Services, New Windsor, NY) dichotomous panel D-15, retinal photography, fluorescein angiography, and CT and MRI scans. RESULTS Within 4 weeks of therapy, visual acuity had improved from 20/32(-2) to 20/16(-1), the visual field had expanded from being circumferentially constricted to within 8 degrees of fixation to normal, and contrast sensitivity improved in all but the lowest spatial frequency (1.5 cycles/degree). No change was observed in lesion size by fundus photography. Improvement has been maintained over 18 months with intermittent SU5416 therapy. CONCLUSIONS We report rapid, extensive, and durable recovery of visual function after systemic administration of the VEGF receptor inhibitor SU5416 to a patient with VHL syndrome and optic nerve head hemangioblastoma. These findings suggest that continued evaluation of VEGF inhibitors for ocular neovascular disorders is warranted.

Use of Joslin Vision Network digital-video nonmydriatic retinal imaging to assess diabetic retinopathy in a clinical program.

Purpose To incorporate a nonmydriatic, digital-video retinal imaging system into a Diabetes Outpatient Intensive Treatment Program and to evaluate the system’s ability to assess diabetic retinopathy (DR), determine follow-up, and appropriately refer to retinal specialist ophthalmologists. Methods Fundus images were obtained according to Joslin Vision Network (JVN) protocol and evaluated by certified JVN readers. Patients with significant retinal disease underwent evaluation by retinal specialists. Results A total of 268 (51.0%) of 525 imaged patients had comprehensive eye examination by a retinal specialist owing to referable JVN-assessed clinical level of DR, nondiabetic ocular disease, ungradeable images, last eye examination ≥12 months prior, or patient request for examination. JVN diagnosis of a clinical level of DR agreed exactly with clinical findings in 388 eyes (72.5%) or within one level in 478 eyes (89.3%). JVN referral based on most severe diagnosis in either eye matched retinal specialist-recommended follow-up in 248/268 of patients (92.5%). A total of 136/525 (25.9%) of JVN patients had nondiabetic ocular abnormalities requiring referral. Conclusions Recommended follow-up from JVN imaging compared favorably to clinical examination by a retinal specialist. Nondiabetic ocular pathology was identified. JVN assessment of DR level compares favorably to clinical practice, potentially improving access to eye care and enhancing diabetes management.

Peripheral Lesions Identified by Mydriatic Ultrawide Field Imaging: Distribution and Potential Impact on Diabetic Retinopathy Severity

OBJECTIVE To assess diabetic retinopathy (DR) as determined by lesions identified using mydriatic ultrawide field imaging (DiSLO200; Optos plc, Scotland, UK) compared with Early Treatment Diabetic Retinopathy Study (ETDRS) 7-standard field film photography. DESIGN Prospective comparative study of DiSLO200, ETDRS 7-standard field film photographs, and dilated fundus examination (DFE). PARTICIPANTS A total of 206 eyes of 103 diabetic patients selected to represent all levels of DR. METHODS Subjects had DiSLO200, ETDRS 7-standard field film photographs, and DFE. Images were graded for severity and distribution of DR lesions. Discrepancies were adjudicated, and images were compared side by side. MAIN OUTCOME MEASURES Distribution of hemorrhage and/or microaneurysm (H/Ma), venous beading (VB), intraretinal microvascular abnormality (IRMA), and new vessels elsewhere (NVE). Kappa (κ) and weighted κ statistics for agreement. RESULTS The distribution of DR severity by ETDRS 7-standard field film photographs was no DR 12.5%; nonproliferative DR mild 22.5%, moderate 30%, and severe/very severe 8%; and proliferative DR 27%. Diabetic retinopathy severity between DiSLO200 and ETDRS film photographs matched in 80% of eyes (weighted κ = 0.74,κ = 0.84) and was within 1 level in 94.5% of eyes. DiSLO200 and DFE matched in 58.8% of eyes (weighted κ = 0.69,κ = 0.47) and were within 1 level in 91.2% of eyes. Forty eyes (20%) had DR severity discrepancies between DiSLO200 and ETDRS film photographs. The retinal lesions causing discrepancies were H/Ma 52%, IRMA 26%, NVE 17%, and VB 4%. Approximately one-third of H/Ma, IRMA, and NVE were predominantly outside ETDRS fields. Lesions identified on DiSLO200 but not ETDRS film photographs suggested a more severe DR level in 10% of eyes. Distribution in the temporal, superotemporal, inferotemporal, superonasal, and inferonasal fields was 77%, 72%, 61%, 65%, and 59% for H/Ma, respectively (P<0.0001); 22%, 24%, 21%, 28%, and 22% for VB, respectively (P = 0.009); 52%, 40%, 29%, 47%, and 36% for IRMA, respectively (P<0.0001), and 8%, 4%, 4%, 8%, and 5% for NVE, respectively (P = 0.03). All lesions were more frequent in the temporal fields compared with the nasal fields (P<0.0001). CONCLUSIONS DiSLO200 images had substantial agreement with ETDRS film photographs and DFE in determining DR severity. On the basis of DiSLO200 images, significant nonuniform distribution of DR lesions was evident across the retina. The additional peripheral lesions identified by DiSLO200 in this cohort suggested a more severe assessment of DR in 10% of eyes than was suggested by the lesions within the ETDRS fields. However, the implications of peripheral lesions on DR progression within a specific ETDRS severity level over time are unknown and need to be evaluated prospectively.

Nonmydriatic ultrawide field retinal imaging compared with dilated standard 7-field 35-mm photography and retinal specialist examination for evaluation of diabetic retinopathy.

PURPOSE To compare nonmydriatic stereoscopic Optomap ultrawide field images with dilated stereoscopic Early Treatment Diabetic Retinopathy Study 7-standard field 35-mm color 30-degree fundus photographs (ETDRS photography) and clinical examination for determining diabetic retinopathy (DR) and diabetic macular edema (DME) severity. DESIGN Single-site, prospective, comparative, instrument validation study. METHODS One hundred three diabetic patients (206 eyes) representing the full spectrum of DR severity underwent nonmydriatic ultrawide field 100-degree and 200-degree imaging, dilated ETDRS photography, and dilated fundus examination by a retina specialist. Two independent readers graded images to determine DR and DME severity. A third masked retina specialist adjudicated discrepancies. RESULTS Based on ETDRS photography (n = 200), the results were as follows: no DR (n = 25 eyes [12.5%]), mild nonproliferative DR (NPDR; 47 [23.5%]), moderate NPDR (61 [30.5%]), severe NPDR (11 [5.5%]), very severe NPDR (3 [1.5%]), and proliferative DR (52 [2.5%]). One (0.5%) eye was ungradable and 6 eyes did not complete ETDRS photography. No DME was found in 114 eyes (57.0%), DME was found in 28 eyes (14.0%), and clinically significant DME was found in 47 eyes (23.5%), and 11 (5.5%) eyes were ungradable. Exact DR severity agreement between ultrawide field 100-degree imaging and ETDRS photography occurred in 84%, with agreement within 1 level in 91% (K(W) = 0.85; K = 0.79). Nonmydriatic ultrawide field images exactly matched clinical examination results for DR in 70% and were within 1 level in 93% (K(W) = 0.71; K = 0.61). Nonmydriatic ultrawide field imaging acquisition time was less than half that of dilated ETDRS photography (P < .0001). CONCLUSIONS Nonmydriatic ultrawide field images compare favorably with dilated ETDRS photography and dilated fundus examination in determining DR and DME severity; however, they are acquired more rapidly. If confirmed in broader diabetic populations, nonmydriatic ultrawide field imaging may prove to be beneficial in DR evaluation in research and clinical settings.

Telehealth practice recommendations for diabetic retinopathy, second edition.

Ocular telemedicine and telehealth have the potential to decrease vision loss from DR. Planning, execution, and follow-up are key factors for success. Telemedicine is complex, requiring the services of expert teams working collaboratively to provide care matching the quality of conventional clinical settings. Improving access and outcomes, however, makes telemedicine a valuable tool for our diabetic patients. Programs that focus on patient needs, consider available resources, define clear goals, promote informed expectations, appropriately train personnel, and adhere to regulatory and statutory requirements have the highest chance of achieving success.

Peripheral Lesions Identified on Ultrawide Field Imaging Predict Increased Risk of Diabetic Retinopathy Progression over 4 Years

OBJECTIVE To determine whether peripheral diabetic retinopathy (DR) lesions identified on ultrawide field (UWF) imaging are associated with increased DR progression. DESIGN Prospective, longitudinal cohort. PARTICIPANTS Two hundred eyes of 100 participants previously enrolled in a comparative instrument validation study. METHODS Baseline mydriatic 7-standard field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs and UWF images were obtained. On UWF images, DR lesions with a greater extent outside versus inside standard ETDRS fields were defined as predominantly peripheral lesions (PPLs). Follow-up ETDRS photographs were obtained 4.2±0.3 years after baseline. Baseline and follow-up DR severity were graded from ETDRS photographs. MAIN OUTCOME MEASURES Rates of 2-step or more progression and progression to proliferative DR (PDR) in eyes with PPLs compared with eyes without PPLs identified on UWF imaging at baseline. RESULTS In eyes without PDR (n = 109) at baseline, 56 (51%) had at least 1 field with PPLs and 43 (39%) had DR progression. Compared with eyes without PPLs, eyes with PPLs had a 3.2-fold increased risk of 2-step or more DR progression (6 [11%] vs. 19 [34%]; P = 0.005) and a 4.7-fold increased risk for progression to PDR (3 [6%] vs. 14 [25%]; P = 0.005). These findings remained statistically significant after adjusting for gender, diabetes type, diabetes duration, hemoglobin A1c (HbA1c) levels, and baseline DR severity. Increasing extent of fields with PPLs increased the risk for 2-step or more DR progression (P = 0.004) and progression to PDR (P = 0.009). CONCLUSIONS Presence and increasing extent of PPLs were associated with increased risk of DR progression over 4 years, independent of baseline DR severity and HbA1c levels. Increasing extent of PPLs substantially increased the risk of DR progression and progression to PDR, especially with less severe DR at baseline. These findings demonstrate that detailed peripheral retinal evaluation provides important information that is necessary to assess completely the risk of DR progression.

Nonmydriatic teleretinal imaging improves adherence to annual eye examinations in patients with diabetes.

We studied whether nonmydriatic digital retinal imaging with remote interpretation (teleretinal imaging) in the ambulatory care setting affected adherence to annual dilated eye examinations among patients with diabetes. We randomly assigned 448 patients to a teleretinal imaging group or a control group. We measured the number of patients who had dilated eye examinations within 12 months of group assignment and the agreement for level of diabetic retinopathy between teleretinal imaging and the eye examinations. The teleretinal imaging group (n = 223) had significantly more dilated eye examinations than the control group (n = 225). Teleretinal imaging and eye examination results showed significant correlation and moderate agreement. Cataract and smaller pupil size were significantly associated with ungradable retinal images. Two-thirds of patients with ungradable images had other ocular findings. Patients reported high satisfaction with nonmydriatic teleretinal imaging. Nonmydriatic teleretinal imaging improves diabetic retinopathy assessment rates.

Potential Efficiency Benefits of Nonmydriatic Ultrawide Field Retinal Imaging in an Ocular Telehealth Diabetic Retinopathy Program

OBJECTIVE To compare efficiency of nonmydriatic ultrawide field retinal imaging (UWFI) and nonmydriatic fundus photography (NMFP) in a diabetic retinopathy (DR) ocular telehealth program. RESEARCH DESIGN AND METHODS Patients in this retrospective, comparative cohort study underwent NMFP and UWFI between 1 November 2011 and 1 November 2012. Images were evaluated for DR and diabetic macular edema (DME) by certified graders using a standard protocol at a centralized reading center. Identification of DR, image evaluation time, and rate of ungradable eyes were compared. RESULTS NMFP and UWFI were performed in 1,633 and 2,170 consecutive patients, respectively. No statistically significant differences were found between groups regarding age, diabetes duration, sex, ethnicity, or insulin use. The ungradable rate per patient for DR (2.9 vs. 9.9%, P < 0.0001) and DME (3.8 vs. 8.8%, P < 0.0001) was lower with UWFI than with NMFP. With UWFI, the median image evaluation time per patient was reduced from 12.8 to 9.2 min (P < 0.0001). The identification of patients with DR (38.4 vs. 33.8%) and vision-threatening DR (14.5 vs. 11.9%) was increased with UWFI versus NMFP. In a consecutive subgroup of 502 eyes of 301 patients with DR, the distribution of peripheral retinal lesions outside Early Treatment Diabetic Retinopathy Study fields suggested a more severe DR level in 9.0% (45 eyes). CONCLUSIONS In a standardized DR ocular telehealth program, nonmydriatic UWFI reduced the ungradable rate by 71% (to <3%) and reduced image evaluation time by 28%. DR was identified 17% more frequently after UWFI, and DR peripheral lesions suggested a more severe DR level in 9%. These data suggest that UWFI may improve efficiency of ocular telehealth programs evaluating DR and DME.