Diabetic retinopathy (DR) is one of the leading causes of blindness in the United States and world-wide. DR is a silent disease that may go unnoticed until it is too late for effective treatment. ...Therefore, early detection could improve the chances of therapeutic interventions that would alleviate its effects.
Graded fundus photography and systemic data from 3443 ACCORD-Eye Study participants were used to estimate Random Forest (RF) and logistic regression classifiers. We studied the impact of sample size on classifier performance and the possibility of using RF generated class conditional probabilities as metrics describing DR risk. RF measures of variable importance are used to detect factors that affect classification performance.
Both types of data were informative when discriminating participants with or without DR. RF based models produced much higher classification accuracy than those based on logistic regression. Combining both types of data did not increase accuracy but did increase statistical discrimination of healthy participants who subsequently did or did not have DR events during four years of follow-up. RF variable importance criteria revealed that microaneurysms counts in both eyes seemed to play the most important role in discrimination among the graded fundus variables, while the number of medicines and diabetes duration were the most relevant among the systemic variables.
We have introduced RF methods to DR classification analyses based on fundus photography data. In addition, we propose an approach to DR risk assessment based on metrics derived from graded fundus photography and systemic data. Our results suggest that RF methods could be a valuable tool to diagnose DR diagnosis and evaluate its progression.
To determine whether home monitoring with the ForeseeHome device (Notal Vision Ltd, Tel Aviv, Israel), using macular visual field testing with hyperacuity techniques and telemonitoring, results in ...earlier detection of age-related macular degeneration-associated choroidal neovascularization (CNV), reflected in better visual acuity, when compared with standard care. The main predictor of treatment outcome from anti-vascular endothelial growth factor (VEGF) agents is the visual acuity at the time of CNV treatment.
Unmasked, controlled, randomized clinical trial.
One thousand nine hundred and seventy participants 53 to 90 years of age at high risk of CNV developing were screened. Of these, 1520 participants with a mean age of 72.5 years were enrolled in the Home Monitoring of the Eye study at 44 Age-Related Eye Disease Study 2 clinical centers.
In the standard care and device arms arm, investigator-specific instructions were provided for self-monitoring vision at home followed by report of new symptoms to the clinic. In the device arm, the device was provided with recommendations for daily testing. The device monitoring center received test results and reported changes to the clinical centers, which contacted participants for examination.
The main outcome measure was the difference in best-corrected visual acuity scores between baseline and detection of CNV. The event was determined by investigators based on clinical examination, color fundus photography, fluorescein angiography, and optical coherence tomography findings. Masked graders at a central reading center evaluated the images using standardized protocols.
Seven hundred sixty-three participants were randomized to device monitoring and 757 participants were randomized to standard care and were followed up for a mean of 1.4 years between July 2010 and April 2013. At the prespecified interim analysis, 82 participants progressed to CNV, 51 in the device arm and 31 in the standard care arm. The primary analysis achieved statistical significance, with the participants in the device arm demonstrating a smaller decline in visual acuity with fewer letters lost from baseline to CNV detection (median, -4 letters; interquartile range IQR, -11.0 to -1.0 letters) compared with standard care (median, -9 letters; IQR, -14.0 to -4.0 letters; P = 0.021), resulting in better visual acuity at CNV detection in the device arm. The Data and Safety Monitoring Committee recommended early study termination for efficacy.
Persons at high risk for CNV developing benefit from the home monitoring strategy for earlier detection of CNV development, which increases the likelihood of better visual acuity results after intravitreal anti-VEGF therapy.
The Geographic Atrophy Progression (GAP) study was designed to assess the rate of geographic atrophy (GA) progression and to identify prognostic factors by measuring the enlargement of the atrophic ...lesions using fundus autofluorescence (FAF) and color fundus photography (CFP).
Prospective, multicenter, noninterventional natural history study.
A total of 603 participants were enrolled in the study; 413 of those had gradable lesion data from FAF or CFP, and 321 had gradable lesion data from both FAF and CFP.
Atrophic lesion areas were measured by FAF and CFP to assess lesion progression over time. Lesion size assessments and best-corrected visual acuity (BCVA) were conducted at screening/baseline (day 0) and at 3 follow-up visits: month 6, month 12, and month 18 (or early exit).
The GA lesion progression rate in disease subgroups and mean change from baseline visual acuity.
Mean (standard error) lesion size changes from baseline, determined by FAF and CFP, respectively, were 0.88 (0.1) and 0.78 (0.1) mm(2) at 6 months, 1.85 (0.1) and 1.57 (0.1) mm(2) at 12 months, and 3.14 (0.4) and 3.17 (0.5) mm(2) at 18 months. The mean change in lesion size from baseline to month 12 was significantly greater in participants who had eyes with multifocal atrophic spots compared with those with unifocal spots (P < 0.001) and those with extrafoveal lesions compared with those with foveal lesions (P = 0.001). The mean (standard deviation) decrease in visual acuity was 6.2 ± 15.6 letters for patients with image data available. Atrophic lesions with a diffuse (mean 0.95 mm(2)) or banded (mean 1.01 mm(2)) FAF pattern grew more rapidly by month 6 compared with those with the "none" (mean, 0.13 mm(2)) and focal (mean, 0.36 mm(2)) FAF patterns.
Although differences were observed in mean lesion size measurements using FAF imaging compared with CFP, the measurements were highly correlated with one another. Significant differences were found in lesion progression rates in participants stratified by hyperfluorescence pattern subtype. This large GA natural history study provides a strong foundation for future clinical trials.
To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD).
Consensus meeting.
Panel of retina specialists, ...image reading center experts, retinal histologists, and optics engineers.
As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy.
A consensus classification system for atrophy and OCT-based criteria to identify atrophy.
OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear.
A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete representation of changes that occur in AMD than can be detected using color fundus photography alone. Longitudinal information is required to validate the implied risk of vision loss associated with these terms. This system will enable such future studies to be undertaken using consistent definitions.
To develop a parameter that can assess the relative rate of progression of geographic atrophy (GA) based on the hypothesis that noncircular configuration of the atrophic lesion may be a risk factor ...for enlargement.
Cohort study.
Digitized color photographs of 593 eyes with GA from the Age-Related Eye Disease Study (AREDS).
A novel parameter called the "Geographic Atrophy Circularity Index" (GACI) was developed on the basis of area and perimeter measurements to categorize the irregularity of the shape of GA. The GACI ranges from 0.0 to 1.0 and is categorized into 3 groups: 0.25 (very irregular), 0.25 to <0.75 (partly irregular), and ≥ 0.75 (circular).
Growth rate of GA.
The mean growth rate in the 3 categories was 0.40 (± 0.18), 0.36 (± 0.30), and 0.21 (± 0.22) mm/year, respectively (P < 0.001). By adjusting for known confounders, baseline area, duration of GA, and configuration, GACI categories were significantly associated with increased growth rate of GA (P < 0.001).
The GACI was associated with the progression rate of GA and may be a useful measure for clinical trial eligibility. The association also suggests that enlargement of GA may be related to the extent of the junctional zone of damaged retinal pigment epithelium, which increases with noncircularity for a given GA area.
To report additional ocular outcomes of intensive treatment of hyperglycemia, blood pressure, and dyslipidemia in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.
Double 2×2 ...factorial, multicenter, randomized clinical trials in people with type 2 diabetes who had cardiovascular disease or cardiovascular risk factors. In the glycemia trial, targets of intensive and standard treatment were: hemoglobin A1c <6.0% and 7.0% to 7.9%, respectively, and in the blood pressure trial: systolic blood pressures of <120 and <140 mmHg, respectively. The dyslipidemia trial compared fenofibrate plus simvastatin with placebo plus simvastatin.
Of the 3472 ACCORD Eye Study participants enrolled, 2856 had 4-year data (85% of survivors).
Eye examinations and fundus photographs were taken at baseline and year 4. Photographs were graded centrally for retinopathy severity and macular edema using the Early Treatment Diabetic Retinopathy Study (ETDRS) methods.
Three or more steps of progression on the ETDRS person scale or treatment of retinopathy with photocoagulation or vitrectomy.
As previously reported, there were significant reductions in the primary outcome in the glycemia and dyslipidemia trials, but no significant effect in the blood pressure trial. Results were similar for retinopathy progression by 1, 2, and 4 or more steps on the person scale and for ≥ 2 steps on the eye scale. In the subgroup of patients with mild retinopathy at baseline, effect estimates were large (odds ratios, ∼0.30; P < 0.001), but did not reach nominal significance for participants with no retinopathy or for those with moderate to severe retinopathy at baseline.
Slowing of progression of retinopathy by intensive treatment of glycemia was observed in ACCORD participants, whose average age and diabetes duration were 62 and 10 years, respectively, and who had cardiovascular disease or cardiovascular risk factors. The effect seemed stronger in patients with mild retinopathy. Similar slowing of progression was observed in patients treated with fenofibrate, with no effect observed with intensive blood pressure treatment. This is the second study to confirm the benefits of fenofibrate in reducing diabetic retinopathy progression, and fenofibrate should be considered for treatment of diabetic retinopathy.
To describe the prevalence and interrelationships of epiretinal membranes (ERMs), vitreomacular traction (VMT), macular cysts, paravascular cysts (PVCs), lamellar macular holes (LMHs), full-thickness ...macular holes (FTMHs), and visual impairment in a population-based study of older adults.
Cross-sectional study.
There were 1913 participants aged 63 to 102 years at the 20-year Beaver Dam Eye Study follow-up examination in 2008-2010, of whom 1540 (2980 eyes) had gradable spectral-domain optical coherence tomography (SD OCT) scans of the macula in at least 1 eye.
The presence of ERMs and other retinal lesions was determined by standardized grading of macular SD OCT scans and photographs of 3 standard fields.
Epiretinal membranes, VMT, macular cysts, PVCs, LMHs, FTMHs, and visual impairment.
By using SD OCT, the prevalence of ERMs (34.1%), VMT (1.6%), macular cysts (5.6%), PVCs (20.0%), LMHs (3.6%), and FTMHs (0.4%) was estimated. The prevalence of macular cysts (P < 0.001), ERMs (P < 0.001), and VMT (P = 0.005) increased with age; the prevalence of PVCs (P = 0.05) decreased with age; and the prevalence of LMHs was not associated with age (P = 0.70). The prevalence of macular cysts, LMHs, and ERMs was higher in eyes with a history of cataract surgery. Macular cysts and ERMs were more common in eyes with retinal diseases, such as proliferative diabetic retinopathy, retinal vein occlusion, and retinal detachment, than in eyes without these conditions. Macular cysts, ERMs, and FTMHs were associated with visual impairment. While adjusting for age and sex, macular cysts (odds ratio OR, 3.96; P < 0.0001), PVCs (OR, 1.45, P = 0.007), LMHs (OR, 10.62; P < 0.001), VMT (OR, 2.72, P = 0.01), and visual impairment (OR, 3.23; P < 0.001) were more frequent in eyes with ERMs compared with eyes without ERMs.
Epiretinal membranes are associated with macular cysts, PVCs, LMHs, VMT, and visual impairment. Further follow-up will allow better understanding of the natural history of ERMs and VMT and their relationships to the development of macular cysts and LMHs in the aging population.
To evaluate choroidal and suprachoroidal changes following suprachoroidal injection of triamcinolone acetonide injectable suspension (CLS-TA), in eyes with macular edema due to retinal vein occlusion ...(RVO).
Prospective cohort study within a randomized, controlled phase 2 clinical trial.
Enhanced depth imaging optical coherence tomography (EDI-OCT) images were analyzed from 38 eyes of 38 treatment-naïve patients with macular edema due to RVO, enrolled in the prospective Suprachoroidal Injection of Triamcinolone Acetonide with Intravitreal Aflibercept in Subjects with Macular Edema Due to Retinal Vein Occlusion (TANZANITE) study who received either a suprachoroidal injection of CLS-TA with an intravitreal injection of aflibercept (combination arm) or only an intravitreal injection of aflibercept (monotherapy arm), followed by monthly intravitreal aflibercept injections in both arms based on pro re nata criteria.
Macular choroidal thickness measured to the outer choroidal vessel lumen (vascular choroidal thickness, VCT), outer choroid stroma (stromal choroidal thickness, SCT), or inner scleral border (total choroidal thickness, TCT) showed no significant changes over 3 months in both study arms (P = .231-.342). Eyes that received combination therapy showed a trend toward thickening of the suprachoroidal space (SCS) compared with monotherapy alone (13.4 μm vs 5.3 μm at 3 months; P = .077). In the 15 eyes that demonstrated a visible SCS at baseline, the SCS expanded significantly after suprachoroidal CLS-TA injection (16.2 μm to 27.8 μm at 3 months; P = .033).
Suprachoroidal injection of CLS-TA does not alter choroidal thickness in eyes with macular edema due to RVO, but may result in expansion of the SCS.
The aim of this study was to examine differences between adolescents and adults in persistence of the benefits of intensive therapy 10 years after completion of the Diabetes Control and Complications ...Trial (DCCT).
During the Epidemiology of Diabetes Interventions and Complications (EDIC) study, progression of retinopathy from DCCT closeout to EDIC year 10 was evaluated in 1,055 adults and 156 adolescents.
During 10 years of follow-up, HbA(1c) (A1C) was similar between original intensive (INT) and conventional (CON) groups and between former adolescents and adults. At EDIC year 10, adults in the former INT group continued to show slower progression of diabetic retinopathy than those in the CON group (adjusted hazard reduction 56%, P < 0.0001), whereas in adolescents this beneficial effect had disappeared (32%, P = 0.13). Seventy-nine percent of observed differences in the prolonged treatment effect between adults and adolescents at year 10 were explained by differences in mean A1C during DCCT between adolescents and adults (8.9 vs. 8.1%), particularly between INT adolescents and adults (8.1 vs. 7.2%).
Prior glycemic control during DCCT is vital for the persistence of the beneficial effects of INT therapy 10 years later. Lowering A1C to as close to normal as safely possible without severe hypoglycemia and starting as early as possible should be attempted for all subjects with type 1 diabetes. These results underscore the importance of maintaining A1C at target values for as long as possible because the benefits of former INT treatment wane over time if A1C levels rise.
The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy reduced the development and progression of retinopathy in type 1 diabetes (T1D) compared with conventional ...therapy. The Epidemiology of Diabetes Interventions and Complications (EDIC) study observational follow-up showed persistent benefits. In addition to glycemia, we now examine other potential retinopathy risk factors (modifiable and nonmodifiable) over more than 30 years of follow-up in DCCT/EDIC.
The retinopathy outcomes were proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), and ocular surgery. The survival (event-free) probability was estimated using the Kaplan-Meier method. Cox proportional hazards models assessed the association between risk factors and subsequent risk of retinopathy. Both forward- and backward-selection approaches determined the multivariable models.
Rate of ocular events per 1,000 person-years was 12 for PDR, 14.5 for CSME, and 7.6 for ocular surgeries. Approximately 65%, 60%, and 70% of participants remained free of PDR, CSME, and ocular surgery, respectively. The greatest risk factors for PDR in descending order were higher mean HbA
, longer duration of T1D, elevated albumin excretion rate (AER), and higher mean diastolic blood pressure (DBP). For CSME, risk factors, in descending order, were higher mean HbA
, longer duration of T1D, and greater age and DBP and, for ocular surgeries, were higher mean HbA
, older age, and longer duration of T1D.
Mean HbA
was the strongest risk factor for the progression of retinopathy. Although glycemic control is important, elevated AER and DBP were other modifiable risk factors associated with the progression of retinopathy.
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