Diabetic Retinopathy Lesion Types and Distribution on Ultrawide Field Imaging and the Risk of Disease Worsening Over Time.

PURPOSE: To evaluate the effect of diabetic retinopathy (DR) lesion type [hemorrhages and/or microaneurysms (H/Ma), intraretinal microvascular abnormalities (IRMA), new vessels elsewhere (NVE), venous beading], severity and distribution on disease worsening based on the Early Treatment Diabetic Retinopathy Study (ETDRS)-Diabetic Retinopathy Severity Scale (DRSS). METHODS: Post-hoc analysis of a multi-center observational study of 544 eyes with nonproliferative DR and an ETDRS-DRSS score of Level 35-53. Disease worsening was defined as ETDRS-DRSS worsening by ≥2 steps from baseline or receipt of DR treatment over 4 years. DR lesions were evaluated based on the entire visible area in the ultrawide field color (UWF-color) and UWF-fluorescein angiography (UWF-FA) images. RESULTS: A significantly greater risk of disease worsening was associated with the presence of more severe lesion grades outside the ETDRS fields for H/Ma (HR:1.74 [95% CI:1.28-2.36]) on UWF-color; and for H/Ma (1.90 [1.38-2.61]), IRMA (1.68 [1.13-2.49]), and NVE (1.99 [1.36-2.93]) on UWF-FA. CONCLUSION: These results suggest that features on UWF-color and UWF-FA may provide additional prognostic value in determining the risk of disease worsening. The use of UWF-FA improves identification of DR lesions and disease progression. However, the optimal method of disease risk assessment on UWF imaging still needs to be determined.

INTEGRATING MACULAR OPTICAL COHERENCE TOMOGRAPHY WITH ULTRAWIDE-FIELD IMAGING IN A DIABETIC RETINOPATHY TELEMEDICINE PROGRAM USING A SINGLE DEVICE.

PURPOSE: To determine the effect of combined macular spectral-domain optical coherence tomography (SD-OCT) and ultrawide field retinal imaging (UWFI) within a telemedicine program. METHODS: Comparative cohort study of consecutive patients with both UWFI and SD-OCT. Ultrawide field retinal imaging and SD-OOCT were independently evaluated for diabetic macular edema (DME) and nondiabetic macular abnormality. Sensitivity and specificity were calculated with SD-OCT as the gold standard. RESULTS: Four hundred twenty-two eyes from 211 diabetic patients were evaluated. Diabetic macular edema severity by UWFI was as follows: no DME 93.4%, noncenter involved DME (nonciDME) 5.1%, ciDME 0.7%, ungradable DME 0.7%. SD-OCT was ungradable in 0.5%. Macular abnormality was identified in 34 (8.1%) eyes by UWFI and in 44 (10.4%) eyes by SD-OCT. Diabetic macular edema represented only 38.6% of referable macular abnormality identified by SD-OCT imaging. Sensitivity/specificity of UWFI compared with SD-OCT was 59%/96% for DME and 33%/99% for ciDME. Sensitivity/specificity of UWFI compared with SDOCT was 3%/98% for epiretinal membrane. CONCLUSION: Addition of SD-OCT increased the identification of macular abnormality by 29.4%. More than 58.3% of the eyes believed to have any DME on UWF imaging alone were false-positives by SD-OCT. The integration of SD-OCT with UWFI markedly increased detection and reduced false-positive assessments of DME and macular abnormality in a teleophthalmology program.

Comparison of Diabetic Retinopathy Lesions Identified Using Ultrawide Field Imaging and Optical Coherence Tomography Angiography.

INTRODUCTION: Optical coherence tomography (OCT) angiography (OCTA) has the potential to influence the diagnosis and management of diabetic eye disease. This study aims to determine the correlation between diabetic retinopathy (DR) findings on ultrawide field (UWF) color photography (UWF-CP), UWF fluorescein angiography (UWF-FA), and OCTA. METHODS: This is a cross-sectional, prospective study. One hundred and fourteen eyes from 57 patients with diabetes underwent mydriatic UWF-CP, UWF-FA, and OCTA. DR severity was assessed. Ischemic areas were identified on UWF-FA using ImageJ and the nonperfusion index (NPI) was calculated. Diabetic macular edema (DME) was assessed using OCT. Superficial capillary plexus vessel density (VD), vessel perfusion (VP), and foveal avascular zone (FAZ) area were automatically measured on OCTA. Pearson correlation coefficient between the imaging modalities was determined. RESULTS: Forty-five eyes were excluded due to non-DR findings or prior laser photocoagulation; 69 eyes were analyzed. DR severity was associated with larger NPI (r = 0.55944, p < 0.0001) even after distinguishing between cones (Cone Nonperfusion Index [CPI]: r = 0.55617, p < 0.0001) and rods (Rod Nonperfusion Index [RPI]: r = 0.55285, p < 0.0001). In eyes with nonproliferative DR (NPDR), NPI is correlated with DME (r = 0.51156, p = 0.0017) and central subfield thickness (CST) (r = 0.67496, p < 0.0001). UWF-FA macular nonperfusion correlated with NPI (r = 0.42899, p = 0.0101), CPI (r = 0.50028, p = 0.0022), and RPI (r = 0.49027, p = 0.0028). Central VD and VP correlated with the DME presence (r = 0.52456, p < 0.0001; r = 0.51952, p < 0.0001) and CST (r = 0.50133, p < 0.0001; r = 0.48731, p < 0.0001). Central VD and VP were correlated with macular nonperfusion (r = 0.44503, p = 0.0065; r = 0.44239, p = 0.0069) in eyes with NPDR. Larger FAZ was correlated with decreased central VD (r = -0.60089, p = 0.0001) and decreased central VP (r = -0.59224, p = 0.0001). CONCLUSION: UWF-CP, UWF-FA, and OCTA findings provide relevant clinical information on diabetic eyes. Nonperfusion on UWF-FA is correlated with DR severity and DME. OCTA metrics of the superficial capillary plexus correlate with the incidence of DME and macular ischemia.

Comparison of 2-Field and 5-Field Mydriatic Handheld Retinal Imaging in a Community-Based Diabetic Retinopathy Screening Program.

INTRODUCTION: The purpose of this study was to compare 2-field (2F) and 5-field (5F) mydriatic handheld retinal imaging for the assessment of diabetic retinopathy (DR) severity in a community-based DR screening program (DRSP). METHODS: This was a prospective, cross-sectional diagnostic study, evaluating images of 805 eyes from 407 consecutive patients with diabetes acquired from a community-based DRSP. Mydriatic standardized 5F imaging (macula, disc, superior, inferior, temporal) with handheld retinal camera was performed. 2F (disc, macula), and 5F images were independently assessed using the International DR classification at a centralized reading center. Simple (K) and weighted (Kw) kappa statistics were calculated for DR. Sensitivity and specificity for referable DR ([refDR] moderate nonproliferative DR [NPDR] or worse) and vision-threatening DR ([vtDR] severe NPDR or worse) for 2F compared to 5F imaging were calculated. RESULTS: Distribution of DR severity by 2F/5F images (%): no DR 66.0/61.7, mild NPDR 10.7/14.4, moderate NPDR 7.9/8.1, severe NPDR 3.3/5.6, proliferative DR 5.6/4.6, ungradable 6.5/5.6. Exact agreement of DR grading between 2F and 5F was 81.7%, within 1-step 97.1% (K = 0.64, Kw = 0.78). Sensitivity/specificity for 2F compared 5F was refDR 0.80/0.97, vtDR 0.73/0.98. The ungradable images rate with 2F was 16.1% higher than with 5F (6.5 vs. 5.6%, p < 0.001). CONCLUSIONS: Mydriatic 2F and 5F handheld imaging have substantial agreement in assessing severity of DR. However, the use of mydriatic 2F handheld imaging only meets the minimum standards for sensitivity and specificity for refDR but not for vtDR. When using handheld cameras, the addition of peripheral fields in 5F imaging further refines the referral approach by decreasing ungradable rate and increasing sensitivity for vtDR.

Comparisons of Handheld Retinal Imaging with Optical Coherence Tomography for the Identification of Macular Pathology in Patients with Diabetes.

INTRODUCTION: Handheld retinal imaging cameras are relatively inexpensive and highly portable devices that have the potential to significantly expand diabetic retinopathy (DR) screening, allowing a much broader population to be evaluated. However, it is essential to evaluate if these devices can accurately identify vision-threatening macular diseases if DR screening programs will rely on these instruments. Thus, the purpose of this study was to evaluate the detection of diabetic macular pathology using monoscopic macula-centered images using mydriatic handheld retinal imaging compared with spectral domain optical coherence tomography (SDOCT). METHODS: Mydriatic 40°-60° macula-centered images taken with 3 handheld retinal imaging devices (Aurora [AU], SmartScope [SS], RetinaVue 700 [RV]) were compared with the Cirrus 6000 SDOCT taken during the same visit. Images were evaluated for the presence of diabetic macular edema (DME) on monoscopic fundus photographs adapted from Early Treatment Diabetic Retinopathy Study (ETDRS) definitions (no DME, noncenter-involved DME [non-ciDME], and center-involved DME [ciDME]). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each device with SDOCT as gold standard. RESULTS: Severity by ETDRS photos: no DR 33.3%, mild NPDR 20.4%, moderate 14.2%, severe 11.6%, proliferative 20.4%, and ungradable for DR 0%; no DME 83.1%, non-ciDME 4.9%, ciDME 12.0%, and ungradable for DME 0%. Gradable images by SDOCT (N = 217, 96.4%) showed no DME in 75.6%, non-ciDME in 9.8%, and ciDME in 11.1%. The ungradable rate for images (poor visualization in >50% of the macula) was AU: 0.9%, SS: 4.4%, and RV: 6.2%. For DME, sensitivity and specificity were similar across devices (0.5-0.64, 0.93-0.97). For nondiabetic macular pathology (ERM, pigment epithelial detachment, traction retinal detachment) across all devices, sensitivity was low to moderate (0.2-0.5) but highly specific (0.93-1.00). CONCLUSIONS: Compared to SDOCT, handheld macular imaging attained high specificity but low sensitivity in identifying macular pathology. This suggests the importance of SDOCT evaluation for patients suspected to have DME on fundus photography, leading to more appropriate referral refinement.

In vivo and in silico comparison analyses of Cry toxin activities toward the sugarcane giant borer.

The sugarcane giant borer, Telchin licus licus, is an insect pest that causes significant losses in sugarcane crops and in the sugar-alcohol sector. Chemical and manual control methods are not effective. As an alternative, in the current study, we have screened Bacillus thuringiensis (Bt) Cry toxins with high toxicity against this insect. Bioassays were conducted to determine the activity of four Cry toxins (Cry1A (a, b, and c) and Cry2Aa) against neonate T. licus licus larvae. Notably, the Cry1A family toxins had the lowest LC50 values, in which Cry1Ac presented 2.1-fold higher activity than Cry1Aa, 1.7-fold larger than Cry1Ab, and 9.7-fold larger than Cry2Aa toxins. In silico analyses were performed as a perspective to understand putative interactions between T. licus licus receptors and Cry1A toxins. The molecular dynamics and docking analyses for three putative aminopeptidase N (APN) receptors (TlAPN1, TlAPN3, and TlAPN4) revealed evidence for the amino acids that may be involved in the toxin-receptor interactions. Notably, the properties of Cry1Ac point to an interaction site that increases the toxin's affinity for the receptor and likely potentiate toxicity. The interacting amino acid residues predicted for Cry1Ac in this work are probably those shared by the other Cry1A toxins for the same region of APNs. Thus, the presented data extend the existing knowledge of the effects of Cry toxins on T. licus licus and should be considered in further development of transgenic sugarcane plants resistant to this major occurring insect pest in sugarcane fields.

Recent assessment and characterization of Tuta absoluta resistance to cartap hydrochloride.

Tuta absoluta can cause 100% loss in tomato yield in Brazil and chemical control, which uses cartap hydrochloride (nereistoxin derivative), is still the most used tactic against T. absoluta populations. Despite the long use of cartap hydrochloride, the genetic and physiological bases underlying the resistance are not known. Resistance to cartap hydrochloride among field populations varied from very low (RR = 2.3 fold) to very high (RR = 537 fold). The Gameleira 2 (GML 2-Res) population was exposed to cartap hydrochloride (up to 500 mg L-1) for few rounds of selection to clean extrinsic factors before used in downstream experiments after 2.5 years without selection in laboratory. Resistance to cartap hydrochloride was autosomal, incompletely recessive, and polyfactorial. The effective dominance (dominance level of survival at a given insecticide dose) at 60 mg of cartap hydrochloride L-1 (which killed 100% of heterozygous individuals) discriminated resistant from susceptible phenotypes. Hydrolases and glutathione S-transferase appear to detoxify cartap hydrochloride as TPP and DEM synergized its toxicity, but CYP450-dependent monooxygenases are as well implicated. Cross-resistance was significant between cartap hydrochloride and methoxyfenozide (RR = 6.99 fold), deltamethrin (RR = 3.57 fold), chlorfenapyr (RR = 3.21 fold), or chlorantraniliprole (RR = 2.83 fold). The characterization of T. absoluta resistance to cartap hydrochloride provides valuable information to refine the management of resistance to insecticides (MRI) program in Brazil with cross resistance pattern very favorable to the rotation of active ingredients that will impair survival of this pest to that insecticide in the field.

Effect of Accessible Nonmydriatic Retinal Imaging on Diabetic Retinopathy Surveillance Rates.

Purpose: To evaluate the impact on surveillance rates for diabetic retinopathy (DR) by providing nonmydriatic retinal imaging as part of comprehensive diabetes care at no cost to patients or insurers. Methods: A retrospective comparative cohort study was designed. Patients were imaged from April 1, 2016 to March 31, 2017 at a tertiary diabetes-specific academic medical center. Retinal imaging was provided without additional cost beginning October 16, 2016. Images were evaluated for DR and diabetic macular edema using standard protocol at a centralized reading center. Diabetes surveillance rates before and after no-cost imaging were compared. Results: A total of 759 and 2,080 patients respectively were imaged before and after offering no-cost retinal imaging. The difference represents a 274% increase in the number of patients screened. Furthermore, there was a 292% and 261% increase in the number of eyes with mild DR and referable DR, respectively. In the comparative 6-month period, 92 additional cases of proliferative DR were identified, estimated to prevent 6.7 cases of severe visual loss with annual cost savings of $180,230 (estimated yearly cost of severe vision loss per person: $26,900). In patients with referable DR, self-awareness was low, with no significant difference in the before and after groups (39.4% vs. 43.8%, p = 0.3725). Conclusions: Providing retinal imaging as part of comprehensive diabetes care substantially increased the number of patients identified by nearly threefold. The data suggest that the removal of out-of-pocket costs substantially increased patient surveillance rates, which may translate to improved long-term patient outcomes.

ASSESSMENT OF FLUORESCEIN ANGIOGRAPHY NONPERFUSION IN EYES WITH DIABETIC RETINOPATHY USING ULTRAWIDE FIELD RETINAL IMAGING.

PURPOSE: Evaluate association of retinal nonperfusion (NP) on ultrawide field (UWF) fluorescein angiography (FA) with diabetic retinopathy (DR) severity and predominantly peripheral lesions (PPL). METHODS: Multicenter observational study, 652 eyes (361 participants) having nonproliferative DR (NPDR) without center-involved diabetic macular edema in at least one eye. Baseline 200° UWF-color and UWF-FA images were graded by a central reading center for color-PPL and FA-PPL, respectively. UWF-FA was graded for NP index within concentric zones: posterior pole (<10 mm from fovea), midperiphery (10-15 mm), and far periphery (>15 mm). RESULTS: Baseline Early Treatment Diabetic Retinopathy Study DR severity was 31.7% no DR/mild NPDR, 24.1% moderate NPDR, 14.0% moderately severe NPDR, 25.6% severe/very severe NPDR, and 4.6% proliferative DR. Worse DR severity was associated with increased NP index overall (P = 0.002), in the posterior pole (P < 0.001), midperiphery (P < 0.001), and far periphery (P = 0.03). On average, 29.6% of imaged retinal NP was in the posterior pole, 33.7% in midperiphery, and 36.7% in far periphery. Increased NP index was associated with FA-PPL (P < 0.001) but not with color-PPL (P = 0.65). CONCLUSION: Approximately, 70% of NP in diabetic eyes is located outside the posterior pole. Increased NP is associated with the presence of FA-PPL, suggesting UWF-FA may better predict future DR worsening than UWF-color alone.

Stabilized Double-Stranded RNA Strategy Improves Cotton Resistance to CBW (Anthonomus grandis).

Cotton is the most important crop for fiber production worldwide. However, the cotton boll weevil (CBW) is an insect pest that causes significant economic losses in infested areas. Current control methods are costly, inefficient, and environmentally hazardous. Herein, we generated transgenic cotton lines expressing double-stranded RNA (dsRNA) molecules to trigger RNA interference-mediated gene silencing in CBW. Thus, we targeted three essential genes coding for chitin synthase 2, vitellogenin, and ecdysis-triggering hormone receptor. The stability of expressed dsRNAs was improved by designing a structured RNA based on a viroid genome architecture. We transformed cotton embryos by inserting a promoter-driven expression cassette that overexpressed the dsRNA into flower buds. The transgenic cotton plants were characterized, and positive PCR transformed events were detected with an average heritability of 80%. Expression of dsRNAs was confirmed in floral buds by RT-qPCR, and the T1 cotton plant generation was challenged with fertilized CBW females. After 30 days, data showed high mortality (around 70%) in oviposited yolks. In adult insects fed on transgenic lines, chitin synthase II and vitellogenin showed reduced expression in larvae and adults, respectively. Developmental delays and abnormalities were also observed in these individuals. Our data remark on the potential of transgenic cotton based on a viroid-structured dsRNA to control CBW.

Pyramiding dsRNAs increases phytonematode tolerance in cotton plants.

MAIN CONCLUSION: Host-derived suppression of nematode essential genes decreases reproduction of Meloidogyne incognita in cotton. Root-knot nematodes (RKN) represent one of the most damaging plant-parasitic nematode genera worldwide. RNAi-mediated suppression of essential nematode genes provides a novel biotechnological strategy for the development of sustainable pest-control methods. Here, we used a Host Induced Gene Silencing (HIGS) approach by stacking dsRNA sequences into a T-DNA construct to target three essential RKN genes: cysteine protease (Mi-cpl), isocitrate lyase (Mi-icl), and splicing factor (Mi-sf), called dsMinc1, driven by the pUceS8.3 constitutive soybean promoter. Transgenic dsMinc1-T4 plants infected with Meloidogyne incognita showed a significant reduction in gall formation (57-64%) and egg masses production (58-67%), as well as in the estimated reproduction factor (60-78%), compared with the susceptible non-transgenic cultivar. Galls of the RNAi lines are smaller than the wild-type (WT) plants, whose root systems exhibited multiple well-developed root swellings. Transcript levels of the three RKN-targeted genes decreased 13- to 40-fold in nematodes from transgenic cotton galls, compared with those from control WT galls. Finally, the development of non-feeding males in transgenic plants was 2-6 times higher than in WT plants, indicating a stressful environment for nematode development after RKN gene silencing. Data strongly support that HIGS of essential RKN genes is an effective strategy to improve cotton plant tolerance. This study presents the first application of dsRNA sequences to target multiple genes to promote M. incognita tolerance in cotton without phenotypic penalty in transgenic plants.

Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy, Third Edition.

Contributors The following document and appendices represent the third edition of the Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy. These guidelines were developed by the Diabetic Retinopathy Telehealth Practice Guidelines Working Group. This working group consisted of a large number of subject matter experts in clinical applications for telehealth in ophthalmology. The editorial committee consisted of Mark B. Horton, OD, MD, who served as working group chair and Christopher J. Brady, MD, MHS, and Jerry Cavallerano, OD, PhD, who served as cochairs. The writing committees were separated into seven different categories. They are as follows: 1.Clinical/operational: Jerry Cavallerano, OD, PhD (Chair), Gail Barker, PhD, MBA, Christopher J. Brady, MD, MHS, Yao Liu, MD, MS, Siddarth Rathi, MD, MBA, Veeral Sheth, MD, MBA, Paolo Silva, MD, and Ingrid Zimmer-Galler, MD. 2.Equipment: Veeral Sheth, MD (Chair), Mark B. Horton, OD, MD, Siddarth Rathi, MD, MBA, Paolo Silva, MD, and Kristen Stebbins, MSPH. 3.Quality assurance: Mark B. Horton, OD, MD (Chair), Seema Garg, MD, PhD, Yao Liu, MD, MS, and Ingrid Zimmer-Galler, MD. 4.Glaucoma: Yao Liu, MD, MS (Chair) and Siddarth Rathi, MD, MBA. 5.Retinopathy of prematurity: Christopher J. Brady, MD, MHS (Chair) and Ingrid Zimmer-Galler, MD. 6.Age-related macular degeneration: Christopher J. Brady, MD, MHS (Chair) and Ingrid Zimmer-Galler, MD. 7.Autonomous and computer assisted detection, classification and diagnosis of diabetic retinopathy: Michael Abramoff, MD, PhD (Chair), Michael F. Chiang, MD, and Paolo Silva, MD.

Hemorrhage and/or Microaneurysm Severity and Count in Ultrawide Field Images and Early Treatment Diabetic Retinopathy Study Photography.

OBJECTIVE: To evaluate detection of hemorrhage and/or microaneurysm (H/Ma) using ultrawide field (UWF) retinal imaging as compared with standard Early Treatment Diabetic Retinopathy Study (ETDRS) 7-field photographs (ETDRS photos). DESIGN: Single-site comparative study of UWF images and ETDRS photos. PARTICIPANTS: One hundred twenty-six eyes of 69 patients with no diabetic retinopathy (DR) or mild or moderate nonproliferative DR (NPDR). METHODS: Stereoscopic 200° UWF images and stereoscopic 35mm 30° 7-field color photographs were acquired on the same visit. Images were graded for severity and distribution of H/Ma. H/Mas were counted in ETDRS fields 2 to 7 in both ETDRS photos and UWF images. H/Mas in the UWF peripheral fields were also counted. MAIN OUTCOME MEASURES: Kappa (κ) and weighted κ statistics for agreement. Number of H/Ma within and outside ETDRS fields identified in UWF images and ETDRS photos. RESULTS: Distribution of DR severity by ETDRS photos was 24 (19.0%) no DR, 48 (38.1%) mild NPDR, and 54 (42.9%) moderate NPDR. A total of 748 of 756 fields (98.9%) were gradable for H/Mas on ETDRS photos and UWF images. Simple κ/weighted κ statistics for severity of H/Ma: all fields 0.61/0.69, field 2 0.70/0.77, field 3 0.62/0.73, field 4 0.50/0.62, field 5 0.54/0.65, field 6 0.64/0.70, and field 7 0.58/0.63 with overall exact agreement in 81.3% and within 1 step in 97.9% of fields. A greater proportion of fields was graded a more severe H/Ma level in UWF images than in the corresponding ETDRS photos (UWF: 12.7% vs. ETDRS: 6.5%). Evaluating comparable areas in UWF images and ETDRS photos (fields 2-7), a mean of 42.8 H/Mas were identified using ETDRS photos and 48.8 in UWF images (P = 0.10). An additional mean of 21.3 H/Mas (49.8% increase, P < 0.0001) were identified in the peripheral fields of the UWF images. CONCLUSIONS: There is good to excellent agreement between UWF images and ETDRS photos in determining H/Ma severity, with excellent correlation of H/Ma counts within ETDRS photo fields. UWF peripheral fields identified 49.8% more H/Ma, suggesting a more severe H/Ma in 12.7% of eyes. Given the additional lesions detected in peripheral fields and the known risks associated with H/Ma and peripheral lesions, quantification of H/Ma using UWF images may provide a more accurate representation of DR disease activity and potential greater accuracy in predicting DR progression.

Identification of Diabetic Retinopathy and Ungradable Image Rate with Ultrawide Field Imaging in a National Teleophthalmology Program.

PURPOSE: To compare diabetic retinopathy (DR) identification and ungradable image rates between nonmydriatic ultrawide field (UWF) imaging and nonmydriatic multifield fundus photography (NMFP) in a large multistate population-based DR teleophthalmology program. DESIGN: Multiple-site, nonrandomized, consecutive, cross-sectional, retrospective, uncontrolled imaging device evaluation. PARTICIPANTS: Thirty-five thousand fifty-two eyes (17 526 patients) imaged using NMFP and 16 218 eyes (8109 patients) imaged using UWF imaging. METHODS: All patients undergoing Joslin Vision Network (JVN) imaging with either NMFP or UWF imaging from May 1, 2014, through August 30, 2015, within the Indian Health Service-JVN program, which serves American Indian and Alaska Native communities at 97 sites across 25 states, were evaluated. All retinal images were graded using a standardized validated protocol in a centralized reading center. MAIN OUTCOME MEASURES: Ungradable rate for DR and diabetic macular edema (DME). RESULTS: The ungradable rate per patient for DR and DME was significantly lower with UWF imaging compared with NMFP (DR, 2.8% vs. 26.9% [P < 0.0001]; DME, 3.8% vs. 26.2% [P < 0.0001]). Identification of eyes with either DR or referable DR (moderate nonproliferative DR or DME or worse) was increased using UWF imaging from 11.7% to 24.2% (P < 0.0001) and from 6.2% to 13.6% (P < 0.0001), respectively. In eyes with DR imaged with UWF imaging (n = 3926 eyes of 2402 patients), the presence of predominantly peripheral lesions suggested a more severe level of DR in 7.2% of eyes (9.6% of patients). CONCLUSIONS: In a large, widely distributed DR ocular telehealth program, as compared with NMFP, nonmydriatic UWF imaging reduced the number of ungradable eyes by 81%, increased the identification of DR nearly 2-fold, and identified peripheral lesions suggesting more severe DR in almost 10% of patients, thus demonstrating significant benefits of this imaging method for large DR teleophthalmology programs.

Operational Components of Telemedicine Programs for Diabetic Retinopathy.

Diabetic retinopathy is a leading cause of new-onset vision loss worldwide. Treatments supported by large clinical trials are effective in preserving vision, but many persons do not receive timely diagnosis and treatment of diabetic retinopathy, which is typically asymptomatic when most treatable. Telemedicine evaluation to identify diabetic retinopathy has the potential to improve access to care and improve outcomes, but incomplete implementation of published standards creates a risk to program utility and sustainability. In a prior article, we reviewed the literature regarding the impact of imaging device, number and size of retinal images, pupil dilation, type of image grader, and diagnostic accuracy on telemedicine assessment for diabetic retinopathy. This article reviews the literature regarding the impact of automated image grading, cost effectiveness, program standards, and quality assurance (QA) on telemedicine assessment of diabetic retinopathy. Telemedicine assessment of diabetic retinopathy has the potential to preserve vision, but greater attention to development and implementation of standards is needed to better realize its potential.

Clinical Components of Telemedicine Programs for Diabetic Retinopathy.

Diabetic retinopathy is a leading cause of new-onset vision loss worldwide. Treatments supported by large clinical trials are effective in preserving vision, but many persons do not receive timely diagnosis and treatment of diabetic retinopathy, which is typically asymptomatic when most treatable. Telemedicine evaluation to identify diabetic retinopathy has the potential to improve access to care, but there are no universal standards regarding camera choice or protocol for ocular telemedicine. We review the literature regarding the impact of imaging device, number and size of retinal images, pupil dilation, type of image grader, and diagnostic accuracy on telemedicine assessment for diabetic retinopathy. Telemedicine assessment of diabetic retinopathy has the potential to preserve vision, but further development of telemedicine specific technology and standardization of operations are needed to better realize its potential.

Regional Image Features Model for Automatic Classification between Normal and Glaucoma in Fundus and Scanning Laser Ophthalmoscopy (SLO) Images.

Glaucoma is one of the leading causes of blindness worldwide. There is no cure for glaucoma but detection at its earliest stage and subsequent treatment can aid patients to prevent blindness. Currently, optic disc and retinal imaging facilitates glaucoma detection but this method requires manual post-imaging modifications that are time-consuming and subjective to image assessment by human observers. Therefore, it is necessary to automate this process. In this work, we have first proposed a novel computer aided approach for automatic glaucoma detection based on Regional Image Features Model (RIFM) which can automatically perform classification between normal and glaucoma images on the basis of regional information. Different from all the existing methods, our approach can extract both geometric (e.g. morphometric properties) and non-geometric based properties (e.g. pixel appearance/intensity values, texture) from images and significantly increase the classification performance. Our proposed approach consists of three new major contributions including automatic localisation of optic disc, automatic segmentation of disc, and classification between normal and glaucoma based on geometric and non-geometric properties of different regions of an image. We have compared our method with existing approaches and tested it on both fundus and Scanning laser ophthalmoscopy (SLO) images. The experimental results show that our proposed approach outperforms the state-of-the-art approaches using either geometric or non-geometric properties. The overall glaucoma classification accuracy for fundus images is 94.4% and accuracy of detection of suspicion of glaucoma in SLO images is 93.9 %.

Diabetic Retinopathy Severity and Peripheral Lesions Are Associated with Nonperfusion on Ultrawide Field Angiography.

PURPOSE: To assess whether the presence of peripheral nonperfusion on ultrawide field (UWF) fluorescein angiography (FA) is associated with diabetic retinopathy (DR) severity and the presence of predominantly peripheral lesions (PPLs). DESIGN: Single-site, cross-sectional, retrospective study. PARTICIPANTS: Sixty-eight eyes of 37 diabetic subjects with or without DR and no history of prior panretinal laser photocoagulation. METHODS: Both 200° UWF images and UWF FA images were acquired at the same visit. Early Treatment Diabetic Retinopathy Study (ETDRS) templates were overlaid digitally based on disc and macula location onto stereographically projected UWF images. Images were evaluated for the presence of PPLs, defined as more than 50% of the graded lesion located outside the ETDRS field in each of the 5 extended fields. The UWF-FA images were evaluated by 2 masked, independent graders for extent of retinal nonperfusion area (NPA) and nonperfusion index (NPI; nonperfused/total gradable area). MAIN OUTCOME MEASURES: Association of NPA and NPI with DR severity and presence of PPLs. RESULTS: Distribution of DR severity was as follows: no DR, 8.8% eyes; mild nonproliferative DR (NPDR), 17.6%; moderate NPDR, 32.4%; severe NPDR, 17.6%; proliferative DR (PDR), 19.1%; and high-risk PDR, 4.4%; with PPL present in 61.8%. There was strong intragrader (r = 0.95) and intergrader (r = 0.86) agreement for NPA. Presence of PPLs was associated with increased NPA (191.8 mm(2) vs. 306.1 mm(2); P = 0.0019) and NPI (0.25 vs. 0.43; P = 0.0003). These relationships remained significant after adjusting for DR severity and diabetes duration. In eyes without PDR (n = 52), increasing NPA and NPI was associated with worsening DR (NPA, P = 0.001; NPI, P = 0.0003). NPA and NPI were not associated with clinically significant macular edema (NPA, P = 0.99; NPI, P = 0.67), nor correlated with visual acuity (NPA, r = 0.14, P = 0.23; NPI, r = 0.24, P = 0.05). CONCLUSIONS: Following a standardized protocol, the evaluation of UWF FA for NPA and NPI is reproducible. Both parameters are correlated highly with the presence of PPLs and DR severity. Given that the presence and extent of PPLs have been associated with increased risks of DR progression, the clinical identification of PPLs may reflect closely the extent of nonperfusion and ischemia, thus accounting for the increased risk of progression.

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.

Automated retinal image analysis for diabetic retinopathy in telemedicine.

There will be an estimated 552 million persons with diabetes globally by the year 2030. Over half of these individuals will develop diabetic retinopathy, representing a nearly insurmountable burden for providing diabetes eye care. Telemedicine programmes have the capability to distribute quality eye care to virtually any location and address the lack of access to ophthalmic services. In most programmes, there is currently a heavy reliance on specially trained retinal image graders, a resource in short supply worldwide. These factors necessitate an image grading automation process to increase the speed of retinal image evaluation while maintaining accuracy and cost effectiveness. Several automatic retinal image analysis systems designed for use in telemedicine have recently become commercially available. Such systems have the potential to substantially improve the manner by which diabetes eye care is delivered by providing automated real-time evaluation to expedite diagnosis and referral if required. Furthermore, integration with electronic medical records may allow a more accurate prognostication for individual patients and may provide predictive modelling of medical risk factors based on broad population data.