Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus. The Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE), a prospective study of a subset of ...patients in the randomized controlled clinical ACCORD trial, is being conducted at enrollment and after 4 years of follow-up to assess the progression of DR with standardized comprehensive eye exams and fundus photography of 7 standard stereoscopic fields. This study aims to assess the effects of the ACCORD medical treatment strategies of tight control of glycemia and blood pressure and management of dyslipidemia on the course of DR in patients with type 2 diabetes. Photographs will be evaluated at a centralized location using the modified Early Treatment Diabetic Retinopathy Study (ETDRS) classification. The primary outcome of ACCORD-EYE, which will measure the development and progression of DR, is a composite of (1) progression of DR (≥3 steps on the ETDRS scale), (2) photocoagulation for DR, or (3) vitrectomy for DR. Specifically, the following questions will be addressed: (1) Does a therapeutic strategy targeting a glycosylated hemoglobin (HbA1c ) level <6.0% reduce development and progression of DR more than one targeting an HbA1c level of 7.0%–7.9% (target median level, 7.5%)? (2) In the context of good glycemic control, does a strategy using a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels and a statin to maintain the level of low-density lipoprotein (LDL) cholesterol at <2.59 mmol/L (100 mg/dL) reduce development and progression of DR compared with one using placebo and a statin to treat LDL cholesterol? (3) In the context of good glycemic control, does a strategy targeting a systolic blood pressure level <120 mm Hg reduce development and progression of DR compared with one targeting a level <140 mm Hg? Secondary outcome variables include various levels of loss of visual acuity at 4 years versus baseline, cataract extraction, and the development or progression of diabetic macular edema. Methods to measure DR progression have been incorporated into ACCORD, and complete baseline data have been collected on 3,537 participants. These data will provide valuable information regarding the effects of medical treatment on the prevention and progression of DR.
To evaluate the angiographic findings in eyes from 2 clinical trials of the dexamethasone intravitreal implant (DEX implant) 0.7 mg in the treatment of macular edema (ME) after branch retinal vein ...occlusion (BRVO) or central retinal vein occlusion (CRVO).
Post hoc analysis of pooled data from 2 identical phase 3 clinical trials.
Patients with vision loss as a result of ME (≥ 6 weeks' duration) after BRVO or CRVO for whom angiographic data were available (n = 329 eyes).
Fluorescein angiography (FA) results assessed by masked, certified graders using standardized grading protocols.
The primary outcome measure in the parent studies was change from baseline in best-corrected visual acuity. Prospectively defined secondary outcomes included FA measurements (to assess macular capillary leakage, neovascularization, and nonperfusion) and optical coherence tomography results (to assess central retinal thickness CRT).
At baseline, 42% of eyes in the DEX implant group and 38% of eyes in the sham group had unreadable assessments because of hemorrhage. At day 180, significantly fewer DEX implant-treated eyes (2%) than sham-treated eyes (9%) had unreadable assessments because of hemorrhage (P = 0.029). Among eyes with gradable assessments, the incidence of nonperfusion remained fairly steady from baseline to day 180. The proportion of eyes with active neovascularization increased from baseline to day 180 in the sham group, but stayed relatively constant in the DEX implant group (P = 0.026 for DEX vs. sham). The mean area of overall nonperfusion and the mean area of macular capillary nonperfusion increased from baseline to day 180 in both treatment groups (no statistically significant between-group difference). There was a statistically significant positive correlation between changes in macular leakage and changes in CRT in both the DEX implant group (r = 0.22; 95% confidence interval, 0.03-0.40; P = 0.023) and the sham group (r = 0.29; 95% confidence interval, 0.10-0.46; P = 0.003).
This study demonstrated that the clinical improvements observed with the DEX implant were accompanied by significant improvements in vascular parameters and suggests that treatment with the DEX implant may be associated with some clinically significant improvements in angiographic findings, specifically active neovascularization.
Inexperienced imagers may make multiple attempts and even then fail to become certified - a source of frustration for all involved. Because of the pressures on modern clinical practices for increased ...efficiency and productivity in the face of declining revenue, the clinical site staff member pressed into the role of imager is sometimes incompletely trained for clinical trial work.\n Because digital camera chips handle illumination, contrast, and color balance quite differently from film,5 obtaining images similar to film quality with digital cameras has been challenging. ...it is the diligent efforts of clinical site investigators and staff, and the patients that donate time and their own resources, that create the foundation of ophthalmology clinical research.
Diabetes mellitus is the most common cause of blindness among working-age adults, with a prevalence of 7 - 8% of adults in the USA, and is one of the most common causes of renal failure requiring ...kidney transplant and the most common cause of non-traumatic lower limb amputation in developed nations 1 . The role of the intracellular signaling enzyme protein kinase C (PKC) in the development of diabetic complications has become a field of intense research interest. An inhibitor of the PKC-beta isoform ruboxistaurin (RBX) has in vitro and in vivo benefits in ameliorating disturbances of cell regulation and blood flow related to hyperglycemia. The benefit of RBX for peripheral neuropathy has not been successfully demonstrated in Phase III trials. Although there was a beneficial effect of RBX on nephropathy in a pilot study, there has been no further clinical development for this indication. The major cause of visual disability - diabetic macular edema - seems to respond to RBX treatment with both anatomic and functional benefits. The manufacturer, Eli Lilly Co., has received an approvable letter from the FDA for the prevention of vision loss in patients with diabetic retinopathy with RBX, pending results of additional clinical trials for this indication.
To analyze brightness, contrast, and color balance of digital versus film retinal images in a multicenter clinical trial, to propose a model image from exemplars, and to optimize both image types for ...evaluation of age-related macular degeneration (AMD).
The Age-Related Eye Disease Study 2 (AREDS2) is enrolling subjects from 90 clinics, with three quarters of them using digital and one quarter using film cameras. Image brightness (B), contrast (C), and color balance (CB) were measured with three-color luminance histograms. First, the exemplars (film and digital) from expert groups were analyzed, and an AMD-oriented model was constructed. Second, the impact of B/C/CB on the appearance of typical AMD abnormalities was analyzed. Third, B/C/CB in AREDS2 images were compared between film (156 eyes) and digital (605 eyes), and against the model. Fourth, suboptimal images were enhanced by adjusting B/C/CB to bring them into accord with model parameters.
Exemplar images had similar brightness, contrast, and color balance, supporting an image model. Varying a specimen image through a wide range of B/C/CB revealed greatest contrast of drusen and pigment abnormalities against normal retinal pigment epithelium with the model parameters. AREDS2 digital images were more variable than film, with lower correspondence to our model. Ten percent of digital were too dim and 19% too bright (oversaturated), versus 1% and 4% of film, respectively. On average, digital had lower green channel contrast (giving less retinal detail) than film. Overly red color balance (weaker green) was observed in 23% of digital versus 8% of film. About half of digital (but fewer film) images required enhancement before AMD grading. After optimization of both image types, AREDS2 image quality was judged as good as that in AREDS (all film).
A histogram-based model, derived from exemplars, provides a pragmatic guide for image analysis and enhancement. In AREDS2, the best digital images matched the best film. Overall, however, digital provided lower contrast of retinal detail. Digital images taken with higher G-to-R ratio showed better brightness and contrast management. Optimization of images in the multicenter study helps standardize documentation of AMD (ClinicalTrials.gov NCT00345176).
To evaluate glaucomatous changes in patients with diabetic macular edema (DME) treated with intravitreal implants releasing 0.2 µg/day or 0.5 µg/day fluocinolone acetonide (FAc) (Iluvien 0.2 µg/day; ...Alimera Sciences, Alpharetta, GA) or sham control.
Fundus photographs were assessed to determine clinically significant changes in glaucomatous indicators.
The mean cup-to-disc ratio (CDR) change was similar with all three treatments. Compared with sham control, a significantly greater proportion of patients treated with 0.5 µg/day but not 0.2 µg/day FAc experienced a CDR increase of greater than 0.1. There was no significant increase in the proportion of patients experiencing a CDR increase of greater than 0.2 with either dose of implant versus sham control. Other indicators of glaucomatous change did not differ significantly with treatment. Subgroup analyses showed no differences in cupping based on ocular or baseline characteristics.
Treatment with FAc for 36 months was not associated with significant glaucomatous optic nerve head changes in patients with DME with or without increased intraocular pressure. Ophthalmic Surg Lasers Imaging Retina. 2016;47:418-425..
To evaluate optical coherence tomography (OCT) reproducibility in patients with diabetic macular edema (DME).
Prospective 1-day observational study.
Two hundred twelve eyes of 107 patients with DME ...involving the macular center by clinical examination and OCT central subfield thickness of > or =225 microm.
Retinal thickness was measured with the OCT3 system, and scans were evaluated by a reading center. Reproducibility of retinal thickness measurements was assessed, and 95% confidence intervals (CIs) for a change in thickness were estimated.
Reproducibility of OCT-measured central subfield thickness.
Reproducibility was better for central subfield thickness than for center point thickness (half-width of the 95% CI for absolute change, 38 microm vs. 50 microm, and for relative change, 11% vs. 17%, respectively; P<0.001). The median absolute difference between replicate measurements of the central subfield was 7 microm (2%). Half-widths of the 95% CI for a change in central subfield thickness were 22, 23, 33, and 56 microm for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. When expressed as percentage differences between 2 measurements, half-widths of the 95% CI for a change in central subfield thickness were 10%, 10%, 10%, and 13% for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. We were unable to identify an effect on reproducibility of central subfield measurements with respect to the presence of cystoid abnormalities, subretinal fluid, vitreomacular traction, or reduced visual acuity. Reproducibility was better when both scans had a standard deviation (SD) of the center point of <10.0% (half-width of the 95% CI for change, 33 microm vs. 56 microm; P<0.001).
Reproducibility is better for central subfield thickness measurements than for center point measurements, and variability is less with retinal thickness when expressed as a percent change than when expressed as an absolute change. A change in central subfield thickness exceeding 11% is likely to be real. Scans with an SD of the center point of > or =10.0% are less reproducible and should be viewed with caution when assessing the validity of an observed change in retinal thickness in patients with DME.
Abstract Objective To evaluate the effects of a home-monitoring device with tele-monitoring compared with standard care in detection of progression to choroidal neovascularization (CNV) associated ...with age-related macular degeneration (AMD), the leading cause of blindness in the US. Patients and methods Participants, aged 55 to 90 years, at high risk of developing CNV associated with AMD were recruited to the HOme Monitoring of Eye (HOME) Study, an unmasked, multi-center, randomized trial of the ForeseeHome (FH) device plus standard care vs. standard care alone. The FH device utilizes preferential hyperacuity perimetry and tele-monitoring to detect changes in vision function associated with development of CNV, potentially prior to symptom and visual acuity loss. After establishing baseline measurements, subsequent changes on follow-up are detected by the device, causing the monitoring center to alert the clinical center to recall participants for an exam. Standard care consists of instructions for self-monitoring visual changes with subsequent self-report to the clinical center. The primary objective of this study is to determine whether home monitoring plus standard care in comparison with standard care alone, results in earlier detection of incident CNV with better present visual acuity. The primary outcome is the decline in visual acuity at CNV diagnosis from baseline. Detection of CNV prior to substantial vision loss is critical as vision outcome following anti-angiogenic therapy is dependent on the visual acuity at initiation of treatment. Discussion HOME Study is the first large scale study to test the use of home tele-monitoring system in the management of AMD patients.
To investigate the effect of optical coherence tomography macular grid displacement on retinal thickness measurements.
SD-OCT macular scans of 66 eyes with various retinal thicknesses were selected. ...Decentration of the 1-, 3-, 6-mm-diameter macular grid was simulated by manually adjusting the distance between center of the fovea (cFovea) and center of the grid (cGrid). Center subfield thickness (CSF) between the internal limiting membrane and the top of the retinal pigment epithelium was measured along the displacement distance where the grid was displaced in eight cardinal directions from the cFovea in steps of 100 μm within the central 1-mm subfield and then by 200 μm within the inner subfields. One-way/mixed-effects repeated-measures ANOVA models were used to determine changes of CSF (ΔCSF) as a function of displacement distance (for α = 0.05, power = 0.80 and effect size = 0.1). The interactions between the displacement distance and direction, center point thickness (CPT), and foveal contour were also analyzed.
The CSF measurement showed statistically significant error when the displacement distance between cFovea and cGrid exceeded 200 μm. The direction of displacement did not affect the ΔCSF-distance relationship, while the CPT and foveal contour significantly affected the relationship, in that some subgroups showed slightly larger tolerance in the displacement distance up to 300 μm before reaching significant ΔCSF.
Small displacement distances of the macular grid from the cFovea affect CSF measurements throughout a broad range of thicknesses and retinal contour alterations from disease. Accurate registration of OCT scans or post hoc repositioning of the grid is essential to optimize CSF accuracy.
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