Central Macular Thickness in Diabetic Patients: A Sex-based Analysis.

SIGNIFICANCE: The pathological changes in clinically significant diabetic macular edema lead to greater retinal thickening in men than in women. Therefore, male sex should be considered a potential risk factor for identifying individuals with the most severe pathological changes. Understanding this excessive retinal thickening in men may help preserve vision. PURPOSE: The purpose of this study was to investigate the sex differences in retinal thickness in diabetic patients. We tested whether men with clinically significant macular edema had even greater central macular thickness than expected from sex differences without significant pathological changes. This study also aimed to determine which retinal layers contribute to abnormal retinal thickness. METHODS: From 2047 underserved adult diabetic patients from Alameda County, CA, 142 patients with clinically significant macular edema were identified by EyePACS-certified graders using color fundus images (Canon CR6-45NM). First, central macular thickness from spectral domain optical coherence tomography (iVue; Optovue Inc.) was compared in 21 men versus 21 women without clinically significant macular edema. Then, a planned comparison contrasted the greater values of central macular thickness in men versus women with clinically significant macular edema as compared with those without. Mean retinal thickness and variability of central macular layers were compared in men versus women. RESULTS: Men without clinically significant macular edema had a 12-µm greater central macular thickness than did women (245 ± 21.3 and 233 ± 13.4 µm, respectively; t40 = -2.18, P = .04). Men with clinically significant macular edema had a 67-µm greater central macular thickness than did women (383 ± 48.7 and 316 ± 60.4 µm, P < .001); that is, men had 55 µm or more than five times more (t20 = 2.35, P = .02). In men, the outer-nuclear-layer thickness was more variable, F10,10 = 9.34. CONCLUSIONS: Underserved diabetic men had thicker retinas than did women, exacerbated by clinically significant macular edema.

Polarization Variability in Age-related Macular Degeneration.

SIGNIFICANCE: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss. Complementary imaging techniques can be used to better characterize and quantify pathological changes associated with AMD. By assessing specific light-tissue interactions, polarization-sensitive imaging can be used to detect tissue disruption early in the disease process. PURPOSE: The aim of this study was to compare variability in central macular polarization properties in patients with nonexudative AMD and age-matched control subjects. METHODS: A scanning laser polarimeter (GDx, LDT/CZM) was used to acquire 15 × 15-degree macular images in 10 subjects diagnosed with nonexudative AMD and 10 age-matched control subjects. The coefficient of variation (COV, SD/mean) was used to quantify variability in pixel intensity in the central 3.3° of the macula for custom images emphasizing multiply scattered light (the depolarized light image) and polarization-retaining light (the maximum of the parallel detector image). The intensity COV was compared across subject categories using paired t tests for each image type. RESULTS: The COV in the central macula was significantly higher in the AMD subject group (average, 0.221; 95% confidence interval [CI], 0.157 to 0.265) when compared with matched control subjects (average 0.120; 95% CI, 0.107 to 0.133) in the depolarized light image (P = .01). The COV in the maximum of the parallel detector image was not statistically different between the two subject groups (AMD average, 0.162 [95% CI, 0.138 to 0.185]; control average, 0.137 [95% CI, 0.115 to 0.158]; P = .21). CONCLUSIONS: Variability in multiply scattered light is higher than that of light that is more polarization preserving in patients with nonexudative AMD. Multiple scattering may act as an early indicator representing disruption to the macula in early AMD.

Subtle changes in diabetic retinas localised in 3D using OCT.

PURPOSE: To detect and localise subtle changes in retinas of diabetic patients who clinically have no diabetic retinopathy (DR) or non-proliferative DR (NPDR) as compared to age- and sex- matched controls. Spectral Domain Optical Coherence Tomography (SD-OCT) and software to examine all retinal layers, including deeper layers, were used to quantify foveal avascular zone size and inner and outer retinal layer thicknesses, as well as to detect axial location of prominent lesions. METHODS: Diabetic subjects, 19 total with 16 having no DR and three having non-proliferative retinopathy, were matched with 19 controls with respect to age and sex. Macular-centred SD-OCT grids of 20 × 15° were taken with the Spectralis. En face or transverse images were generated from the SD-OCT data by automatically segmenting all retinal layers. The transverse images were investigated for foveal avascular zone (FAZ) size, retinal vessel calibre, and structural changes. The size of the FAZ was compared for diabetics vs controls using vendor software and manual marking in Photoshop. Inner retinal layer (IRLFAZ ) and outer nuclear layer (ONLFAZ ) thicknesses at the margins of the FAZ were measured using vendor software. RESULTS: The FAZ area was larger for diabetics (mean ± S.D. = 0.388 ± 0.074 mm2 ) than controls (0.243 ± 0.113 mm2 ), t18 = 5.27, p < 0.0001, using vendor software. The mean IRLFAZ was thicker for the diabetics (86.8 ± 14.5 µm) than controls (65.2 ± 16.3 µm), t18 = 4.59, p = 0.00023, despite lack of exudation by clinical exam. There was no significant association between FAZ area and mean IRLFAZ for the diabetics, r = 0.099, p = 0.69. Vessels not clinically detected were visible in the NFL transverse image of most diabetics, especially for a mild NPDR patient. A prominent lesion found in the en face infra-red image of a mild NPDR subject was localised in the photoreceptor layer by SD-OCT, as well as additional outer retinal changes in other subjects. CONCLUSIONS: Our results demonstrate changes in inner and outer diabetic retinas not readily detectable by clinical exam. IRLFAZ had not thinned at the margins of the large FAZs, indicating neural mass did not yet decrease despite potential ischemia.

Comparison of Cysts in Red and Green Images for Diabetic Macular Edema.

PURPOSE: To investigate whether cysts in diabetic macular edema are better visualized in the red channel of color fundus camera images, as compared with the green channel, because color fundus camera screening methods that emphasize short-wavelength light may miss cysts in patients with dark fundi or changes to outer blood retinal barrier. METHODS: Fundus images for diabetic retinopathy photoscreening were acquired for a study with Aeon Imaging, EyePACS, University of California Berkeley, and Indiana University. There were 2047 underserved, adult diabetic patients, of whom over 90% self-identified as a racial/ethnic identify other than non-Hispanic white. Color fundus images at nominally 45 degrees were acquired with a Canon Cr-DGi non-mydriatic camera (Tokyo, Japan) then graded by an EyePACS certified grader. From the 148 patients graded to have clinically significant macular edema by the presence of hard exudates in the central 1500 µm of the fovea, we evaluated macular cysts in 13 patients with cystoid macular edema. Age ranged from 33 to 68 years. Color fundus images were split into red, green, and blue channels with custom Matlab software (Mathworks, Natick, MA). The diameter of a cyst or confluent cysts was quantified in the red-channel and green-channel images separately. RESULTS: Cyst identification gave complete agreement between red-channel images and the standard full-color images. This was not the case for green-channel images, which did not expose cysts visible with standard full-color images in five cases, who had dark fundi. Cysts appeared more numerous and covered a larger area in the red channel (733 ± 604 µm) than in the green channel (349 ± 433 µm, P < .006). CONCLUSIONS: Cysts may be underdetected with the present fundus camera methods, particularly when short-wavelength light is emphasized or in patients with dark fundi. Longer wavelength techniques may improve the detection of cysts and provide more information concerning the early stages of diabetic macular edema or the outer blood retinal barrier.

Foveal localization in non-exudative AMD using scanning laser polarimetry.

PURPOSE: To determine whether custom scanning laser polarimetry (SLP) images, differing in polarization content, can be used to accurately localize the fovea in the presence of non-exudative age-related macular degeneration (AMD). To determine whether alterations to the foveal structure in non-exudative AMD significantly disrupts the birefringent Henle fiber layer, responsible for the macular cross pattern in some SLP images. To determine whether phase retardation information, specifically color-coded information representing its magnitude and axis, allow better foveal localization than images including retardation amplitude only. METHODS: SLP images were acquired in 25 AMD subjects and 25 age-matched controls. Raw data were used to generate five custom image types differing in polarization content. The foveal location was marked by three graders in each image type for each subject. The difference in variability was compared between the AMD subjects and matched controls. We further determined whether the orientation of Henle fiber layer phase retardation improved localization in 10 subjects with the highest variability in images including only phase retardation amplitude. RESULTS: Images that differed in polarization content led to strikingly different visualizations of AMD pathology. The Henle fiber layer remained sufficiently intact to assist in fovea localization in all subjects but with more variability in the AMD group. For both the AMD and matched control group, images containing birefringence amplitude and orientation information reduced the amount of intragrader, intergrader, and interimage variability for estimating foveal location. CONCLUSIONS: The disruption in Henle fiber birefringence was evident in the eyes with AMD but nevertheless was sufficient to help in foveal localization despite macular pathology. Phase retardation amplitude and axis of orientation can be a useful tool in foveal localization in patients with AMD.

Determination of foveal location using scanning laser polarimetry.

The fovea is the retinal location responsible for our most acute vision. There are several methods used to localize the fovea, but the fovea is not always easily identifiable. Landmarks used to determine the foveal location are variable in normal subjects and localization becomes even more difficult in instances of retinal disease. In normal subjects, the photoreceptor axons that make up the Henle fiber layer are cylindrical and the radial orientation of these fibers is centered on the fovea. The Henle fiber layer exhibits form birefringence, which predictably changes polarized light in scanning laser polarimetry imaging. In this study 3 graders were able to repeatably identify the fovea in 35 normal subjects using near infrared image types with differing polarization content. There was little intra-grader, inter-grader, and inter-image variability in the graded foveal position for 5 of the 6 image types examined, with accuracy sufficient for clinical purposes. This study demonstrates that scanning laser polarimetry imaging can localize the fovea by using structural properties inherent in the central macula.

Henle fiber layer phase retardation changes associated with age-related macular degeneration.

PURPOSE: To quantify and compare phase retardation amplitude and regularity associated with the Henle fiber layer (HFL) between nonexudative AMD patients and age-matched controls using scanning laser polarimetry (SLP) imaging. METHODS: A scanning laser polarimeter was used to collect 15 × 15° macular-centered images in 25 patients with nonexudative AMD and 25 age-matched controls. Raw image data were used to compute macular phase retardation maps associated with the HFL. Consecutive, annular regions of interest from 0.5 to 3.0° eccentricity, centered on the fovea, were used to generate intensity profiles from phase retardation data and analyzed with two complementary techniques: a normalized second harmonic frequency (2f) of the fast Fourier Transform (FFT) analysis and a curve fitting analysis using a 2f sine function. Paired t-tests were used to compare the normalized 2f FFT magnitude at each eccentricity between the two groups, the eccentricity that yielded the maximum normalized 2f FFT between paired individuals across the two groups, and curve fitting RMS error at each eccentricity between the two groups. RESULTS: Normalized 2f FFT components were lower in the AMD group at each eccentricity, with no difference between the two groups in the maximum normalized 2f FFT component eccentricity. The root-mean-square (RMS) error from curve fitting was significantly higher in the AMD group. CONCLUSIONS: Phase retardation changes in the central macula indicate loss and/or structural alterations to central cone photoreceptors in nonexudative AMD patients. Scanning laser polarimetry imaging is a noninvasive method for quantifying cone photoreceptor changes associated with central macular disease.