Abstract:We used a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) to image the retina of subjects with nonproliferative diabetic retinopathy (NPDR). To improve visualization of different retinal features, the size and alignment of the confocal aperture were varied. The inner retinal layers contained clearly visualized retinal vessels. In diabetic subjects there was extensive capillary remodeling despite the subjects having only mild or moderate NPDR. Details of the retinal microvasculature were readily imaged with a larger confocal aperture. Hard exudates were observed with the AOSLO in all imaging modes. Photoreceptor layer images showed regions of bright cones and dark areas, corresponding in location to overlying vascular abnormalities and retinal edema. Clinically undetected intraretinal vessel remodeling and varying blood flow patterns were found. Perifoveal capillary diameters were larger in the diabetic subjects (p<0.01), and small arteriolar walls were thickened, based on wall to lumen measurements (p<.05). The results suggest that existing clinical classifications based on lower magnification clinical assessment may not adequately measure key vascular differences among individuals with NPDR.

PurposeTo compare conventional structural and functional measures of glaucomatous damage with a new functional measure—contrast sensitivity perimetry (CSP-2).MethodsOne eye each was tested for 51 patients with glaucoma and 62 age-similar control subjects using CSP-2, size III 24-2 conventional automated perimetry (CAP), 24-2 frequency-doubling perimetry (FDP), and retinal nerve fiber layer (RNFL) thickness. For superior temporal (ST) and inferior temporal (IT) optic disc sectors, defect depth was computed as amount below mean normal, in log units. Bland-Altman analysis was used to assess agreement on defect depth, using limits of agreement and three indices: intercept, slope, and mean difference. A criterion of p < 0.0014 for significance used Bonferroni correction.ResultsContrast sensitivity perimetry-2 and FDP were in agreement for both sectors. Normal variability was lower for CSP-2 than for CAP and FDP (F > 1.69, p < 0.02), and Bland-Altman limits of agreement for patient data were consistent with variability of control subjects (mean difference, −0.01 log units; SD, 0.11 log units). Intercepts for IT indicated that CSP-2 and FDP were below mean normal when CAP was at mean normal (t > 4, p < 0.0005). Slopes indicated that, as sector damage became more severe, CAP defects for IT and ST deepened more rapidly than CSP-2 defects (t > 4.3, p < 0.0005) and RNFL defects for ST deepened more slowly than for CSP, FDP, and CAP. Mean differences indicated that FDP defects for ST and IT were on average deeper than RNFL defects, as were CSP-2 defects for ST (t > 4.9, p < 0.0001).ConclusionsContrast sensitivity perimetry-2 and FDP defects were deeper than CAP defects in optic disc sectors with mild damage and revealed greater residual function in sectors with severe damage. The discordance between different measures of glaucomatous damage can be accounted for by variability in people free of disease.

PurposePrior studies suggested the use of customized perimetric locations in glaucoma; these studies were limited by imaging only the superficial depths of the retinal nerve fiber layer (RNFL) and by prolonged perimetric testing. We aimed to develop a rapid perimetric test guided by high-resolution images of RNFL bundles.MethodsWe recruited 10 patients with glaucoma, ages 56 to 80 years, median 68 years, and 10 controls, ages 55 to 77 years, median 68 years. The patients were selected based on discrepancies between locations of glaucomatous damage for perimetric and structural measures. Montaging was used to produce optical coherence tomography en face images of the RNFL covering much of the 24-2 grid locations. In experiment 1, we presented the Goldmann size III stimulus at preselected retinal locations of glaucomatous damage, using just two contrasts. In experiment 2, we developed an elongated sinusoidal stimulus, aligned within the defect, to measure contrast sensitivities; abnormalities were defined based on lower 95% reference limits derived from the controls.ResultsThe percentage of predicted locations where size III was not seen at 28 dB ranged from 16% to 80%, with a median of 48%. Contrast sensitivity for the sinusoidal stimulus was below the 95% reference range for 37 of 44 stimuli aligned within the defects.ConclusionsWe developed methods for rapid perimetric testing guided by en face images of the RNFL bundles in patients with glaucoma. Results indicated ganglion cell damage under all of the visible RNFL defects.Translational RelevanceCustomized perimetric locations have potential to improve clinical assessment of glaucoma.

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Purpose: To develop guidelines for engineering perimetric stimuli to reduce testretest variability in glaucomatous defects.Methods: Perimetric testing was performed on one eye for 62 patients with glaucoma and 41 age-similar controls on size III and frequency-doubling perimetry and three custom tests with Gaussian blob and Gabor sinusoid stimuli. Stimulus range was controlled by values for ceiling (maximum sensitivity) and floor (minimum sensitivity). Bland-Altman analysis was used to derive 95% limits of agreement on test and retest, and bootstrap analysis was used to test the hypotheses about peak variability.Results: Limits of agreement for the three custom stimuli were similar in width (0.72 to 0.79 log units) and peak variability (0.22 to 0.29 log units) for a stimulus range of 1.7 log units. The width of the limits of agreement for size III decreased from 1.78 to 1.37 to 0.99 log units for stimulus ranges of 3.9, 2.7, and 1.7 log units, respectively (F ¼ 3.23, P , 0.001); peak variability was 0.99, 0.54, and 0.34 log units, respectively (P , 0.01). For a stimulus range of 1.3 log units, limits of agreement were narrowest with Gabor and widest with size III stimuli, and peak variability was lower (P , 0.01) with Gabor (0.18 log units) and frequency-doubling perimetry (0.24 log units) than with size III stimuli (0.38 log units).Conclusions: Test-retest variability in glaucomatous visual field defects was substantially reduced by engineering the stimuli.Translational Relevance: The guidelines should allow developers to choose from a wide range of stimuli.