Temporal Variation in Optical Coherence Tomography Measurements of Retinal Thickening in Diabetic Macular Edema

A one day study designed to assess the variability of retinal thickening and OCT measurements throughout the day.

Optical Coherence Tomography (OCT) is a noninvasive method for measuring the thickness of the central retina. It has become a standard tool in the management of patients with diabetic macular edema (DME).

OCT is a diagnostic imaging technique, which uses low-coherence interferometry to produce cross-sectional tomograms of the posterior segment eye structures. An 850 nm light source emits a probe beam of infrared light, which is split between the eye and a reference mirror at a known spatial location therefore producing two beams. Both beams are reflected back to a photo detector, the time of flight delay of light back scattered from different layers in the retina is determined, and thickness data are obtained. The OCT's internal computer acquires and processes the data to produce enhanced images. Retinal thickness is determined using many individual A-scans along each of six B-Scans. A computer algorithm is used to determine the inner and outer retinal boundaries for each scan.

The variability of retinal thickening during the day and the variability of OCT measurements in the study of macular edema is an area of considerable interest. A study by Frank et al indicated that OCT retinal thickness measurements in DME vary according to time of day. In that study of 10 subjects, retinal thickness was measured at 8:00 am, 11:00 am, 2:00 pm, and 5:00 pm. There was a decline in the average macular thickness from 8:00 to 11:00 am and relatively little change thereafter. Only four of the 10 subjects had a consistent decrease in the thickening over the course of the day. The eyes with greater retinal thickening tended to show a greater decline over the day than did the eyes with less thickening. The magnitude of the decrease in retinal thickening appeared to be relatively small, although statistically significant. An earlier study by Sternberg et al that employed psychovisual assessments noted that visual function due to macular edema may vary with time of day, generally worse in the morning, which supports the anatomic observations in the study by Frank, et al.

Since OCT is being used as an outcome measure in DME studies, it is important to have more information on its reproducibility as well as more information on the effect of the time of day on retinal thickening.

This study is one of a series of studies being conducted by the Diabetic Retinopathy Clinical Research Network. The study will enroll approximately 100 subjects with DME in at least one eye at participating sites. Subjects will be selected so that there will be approximately 33 eyes with DME in the range of 225 to 300 microns (measured from the center subfield of the OCT3 retina map), 33 in the range of 300 to 450 microns, and 33 with >450 microns. Each subject will have two OCT measurements made on each eye every two hours from 8 am to 4 pm, with an additional measurement at 9 am. Measurements will be made by the same operator using the same OCT3 machine at each time point. The second measurement at each time point may be made by the same or a different operator. Two consecutive fast macular scans of acceptable quality will be submitted (center point thickness with standard deviation less than 10%).

Inclusion Criteria

1. Diagnosis of diabetes mellitus (type 1 or type 2). Any one of the following will be considered sufficient evidence that diabetes is present:
   -Current regular use of insulin for the treatment of diabetes
   -Current regular use of oral antihyperglycemia agents for the treatment of diabetes
   -Documented diabetes by ADA and/or WHO criteria (see Site Coordinator Manual)
2. In at least one eye: (1) definite retinal thickening due to diabetic macular edema based on clinical exam involving the center of the macula, (2) OCT central subfield >=225 microns, and (3) pupil dilates to 5 mm or larger.
3. Able and willing to provide informed consent.

Exclusion Criteria

1. History of chronic renal failure requiring dialysis or kidney transplant.
2. Congestive heart failure currently under treatment.
3. Blood pressure >180/110 (systolic above 180 OR diastolic above 110).

No longer recruiting. Comments: Recruitment has ended.

Completed, with results published. Comments:

The objective of this study was to evaluate diurnal variation in retinal thickness measured with optical coherence tomography (OCT) in patients with center-involved diabetic macular edema. OCT measurements were performed 6 times in a single day between 8 am and 4 pm in 156 eyes of 96 subjects. At 8 am, the average central subfield thickness was 368 microns and the mean visual acuity was approximately 20/50. On average, the change in relative central subfield retinal thickening between 8 am and 4 pm was a decrease of 6% (95% confidence interval, -9% to -3%) and the mean absolute change was a decrease of 13 microns (95% CI, -17 to -8). The absolute change was greater in retinas that were thicker at 8 am (P<.001) but the relative change was not (P = .14). Five eyes of 4 subjects decreased in central subfield thickening by at least 25% and 50 microns at two consecutive time points. Two eyes of 2 subjects had an increase of this same magnitude. The maximum decrease was observed at 4 pm in all 5 eyes. Although throughout the day there are slight decreases on average in retinal thickening, most eyes with diabetic macular edema have little meaningful change in OCT central subfield thickening between 8 am and 4 pm.