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.

Novel Technique for Quantifying Retinal Nerve Fiber Bundle Abnormality in the Temporal Raphe.

SIGNIFICANCE: Glaucomatous nasal visual field abnormalities correspond to damage in the temporal raphe-where individual nerve bundles can be visualized. The ability to quantify structural abnormality in the raphe, with a clinically applicable protocol, sets the stage for investigating the raphe as a potential site for assessing early glaucoma. PURPOSE: To develop a clinically applicable imaging and analysis technique for identifying retinal nerve fiber bundle abnormalities in the temporal raphe. METHODS: Spectralis optical coherence tomography scans customized for the temporal raphe were gathered from 30 younger controls, 30 older controls, and 29 patients with glaucoma. An analysis technique was developed based on the reflectance of the nerve fiber bundles. The technique was first developed in the younger controls, and then applied to the older controls to generate normative data for quantifying nerve fiber bundle reflectance abnormalities in the patients with glaucoma. Matrix perimetric data were gathered in the patients with glaucoma to evaluate the reflectance technique's findings. Reflectance abnormality in the patients was defined when the fraction of enface area showing reflectance abnormality was greater than the 95th percentile estimated from controls. Spearman's rho was used to quantify the relation between the total deviation at the perimetric testing locations and the fraction of corresponding enface area showing reflectance abnormality. RESULTS: Twenty-five of the 29 patients had reflectance abnormalities. Eight of these had mild to no perimetric mean deviation abnormality. Similar results were found when perimetric total deviations were compared to reflectance abnormalities in the corresponding enface locations. Spearman's rho comparing the total deviations to reflectance abnormalities found rs(174) = -0.72, P < .001. CONCLUSIONS: The technique typically identified reflectance abnormality when perimetric abnormality was present. It also identified reflectance abnormalities even when perimetric abnormality was mild or absent. The findings support the potential of raphe imaging in detecting early glaucomatous damage.

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.

A basis for customising perimetric locations within the macula in glaucoma.

PURPOSE: It has been recognised that the 24-2 grid used for perimetry may poorly sample the macula, which has been recently identified as a critical region for diagnosing and managing patients with glaucoma. We compared data derived from patients and controls to investigate the efficacy of a basis for customising perimetric locations within the macula, guided by en face images of retinal nerve fibre layer (RNFL) bundles. METHODS: We used SD-OCT en face montages (www.heidelbergengineering.com) of the RNFL in 10 patients with glaucoma (ages 56-80 years, median 67.5 years) and 30 age-similar controls (ages 47-77, median 58). These patients were selected because of either the absence of perimetric defect while glaucomatous damage to the RNFL bundles was observed, or because of perimetric defect that did not reflect the extent and locations of the glaucomatous damage that appeared in the RNFL images. We used a customised blob stimulus for perimetric testing (a Gaussian blob with 0.25° standard deviation) at 10-2 grid locations, to assess the correspondence between perimetric defects and damaged RNFL bundles observed on en face images and perimetric defects. Data from the age-similar controls were used to compute total deviation (TD) and pattern deviation (PD) values at each location; a perimetric defect for a location was defined as a TD or PD value of -0.5 log unit or deeper. A McNemar's test was used to compare the proportions of locations with perimetric defects that fell outside the damaged RNFL bundles, with and without accounting for displacement of ganglion cell bodies. RESULTS: All patients but one had perimetric defects that were consistent with the patterns of damaged RNFL bundles observed on the en face images. We found six abnormal perimetric locations of 2040 tested in controls and 132 abnormal perimetric locations of 680 tested in patients. The proportions of abnormal locations that fell outside the damaged RNFL bundles, with and without accounting for displacement of the ganglion cell bodies were 0.08 and 0.07, respectively. The difference between the two proportions did not reach statistical significance (p = 0.5 for a one-tailed test). CONCLUSIONS: We demonstrated that it is effective to customise perimetric locations within the macula, guided by en face images of the RNFL bundles. The perimetric losses found with a 10-2 grid demonstrated similar patterns as the damaged RNFL bundles observed on the en face images.

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.

A novel strategy for the estimation of the general height of the visual field in patients with glaucoma.

BACKGROUND: More accurate estimation of the general height of the visual field may improve our ability to detect and monitor progression of diseases affecting visual function such as glaucoma. General height (GH) can be affected by factors such as cataracts, pupillary miosis, refractive error, and learning and fatigue effects. The conventional GH index, consisting of subtracting the 85th largest value from the total-deviation map, has been shown to overestimate the height in patients with moderate and advanced glaucoma. We aimed at developing an improved estimator for general height based on ranking of total-deviation values that are within normal limits (GHr). METHODS: Two datasets were used for the comparisons between GH and GHr estimates: one with 369 visual fields for 102 controls, and another with 500 visual fields for 124 patients. For controls, we compared the distributions of mean of total deviation (MD) and of mean of pattern deviation (MPD) derived from both the GH and the GHr estimates. For patients, we assessed agreement between both estimates and between pairs of consecutive visits. We also compared linear fits in progression analyses. All data were collected with 24-2 SITA Standard. RESULTS: For control subjects and patients with MD above -5.5 dB, estimates with the GHr estimator were not significantly different than with the GH estimator. For patients with glaucoma with MD below -5.5 dB, as MD became more negative the GH estimates were increasingly greater than GHr estimates. For patients with glaucoma, test-retest variability was lower with the GHr estimator: between visits agreement was better for GHr estimates than for GH estimates (SD of 0.8 dB versus 1.5 dB; p < 0.0001). Linear-regression analysis fitted better estimates obtained with the GHr estimator. Root mean square error for GHr was 0.4 dB; lower than the 0.8 dB for GH (p < 0.0001). CONCLUSIONS: The novel GHr estimator is very different from the conventional GH estimator, has more solid foundations, and better statistical properties. Nevertheless, it is not always better than the GH estimator, in particular if no focal loss is present. Pattern-deviation maps obtained with GHr reduce systematic underestimation of glaucomatous damage.

Between-subject variability in asymmetry analysis of macular thickness.

PURPOSE: To investigate the use of asymmetry analysis to reduce between-subject variability of macular thickness measurements using spectral domain optical coherence tomography. METHODS: Sixty-three volunteers (33 young subjects [aged 21 to 35 years] and 30 older subjects [aged 45 to 85 years]) free of eye disease were recruited. Macular images were gathered with the Spectralis optical coherence tomography. An overlay 24- by 24-degree grid was divided into five zones per hemifield, and asymmetry analysis was computed as the difference between superior and inferior zone thicknesses. We hypothesized that the lowest variation and the highest density of ganglion cells will be found approximately 3 to 6 degrees from the foveola, corresponding to zones 1 and 2. For each zone and age group, between-subject SDs were compared for retinal thickness versus asymmetry analysis using an F test. To account for repeated comparisons, p < 0.0125 was required for statistical significance. Axial length and corneal curvature were measured with an IOLMaster. RESULTS: For OD, asymmetry analysis reduced between-subject variability in zones 1 and 2 in both groups (F > 3.2, p < 0.001). Standard deviation for zone 1 dropped from 12.0 to 3.0 µm in the young group and from 11.7 to 2.6 µm in the older group. Standard deviation for zone 2 dropped from 13.6 to 5.3 µm in the young group and from 11.1 to 5.8 µm in the older group. Combining all subjects, neither retinal thickness nor asymmetry analysis showed a strong correlation with axial length or corneal curvature (R² < 0.01). Analysis for OS yielded the same pattern of results, as did asymmetry analyses between eyes (F > 3.8, p < 0.0001). CONCLUSIONS: Asymmetry analysis reduced between-subject variability in zones 1 and 2. Combining the five zones together produced a higher between-subject variation of the retinal thickness asymmetry analysis; thus, we encourage clinicians to be cautious when interpreting the asymmetry analysis printouts.

Contrast sensitivity perimetry and clinical measures of glaucomatous damage.

PURPOSE: To compare conventional structural and functional measures of glaucomatous damage with a new functional measure-contrast sensitivity perimetry (CSP-2). METHODS: One 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. RESULTS: Contrast 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). CONCLUSIONS: Contrast 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.

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.

Customizing Perimetric Locations Based on En Face Images of Retinal Nerve Fiber Bundles With Glaucomatous Damage.

PURPOSE: Prior 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: We 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 RELEVANCE: Customized perimetric locations have potential to improve clinical assessment of glaucoma.

Solitary idiopathic choroiditis.

Solitary idiopathic choroiditis (SIC) is often confused with intraocular masses and inflammatory conditions and has only recently been identified as a distinct clinical condition. Jerry Shields, M.D., was the first to put a name on this condition. The clinical findings and features that distinguish it from other conditions are discussed in this report. A comprehensive examination with supplemental testing such as fluoresceine angiography, B scan, and extensive laboratory workup is necessary to rule out the differentials of SIC. These differentials include inflammatory conditions and retinal and choroidal tumors. SIC has both an active and an inactive phase. The treatment for the condition is controversial. Our patient presented with a suspicious intraocular mass that was diagnosed as SIC after an extensive ocular examination and laboratory workup was completed.

Individual differences in the shape of the nasal visual field.

Between-subject differences in the shape of the nasal visual field were assessed for 103 volunteers 21-85years of age and free of visual disorder. Perimetry was conducted with a stimulus for which contrast sensitivity is minimally affected by peripheral defocus and decreased retinal illumination. One eye each was tested for 103 volunteers free of eye disease in a multi-center prospective longitudinal study. A peripheral deviation index was computed as the difference in log contrast sensitivity at outer (25-29° nasal) and inner (8° from fixation) locations. Values for this index ranged from 0.01 (outer sensitivity slightly greater than inner sensitivity) to -0.7 log unit (outer sensitivity much lower than inner sensitivity). Mean sensitivity for the inner locations was independent of the deviation index (R2<1%), while mean sensitivity for the outer locations was not (R2=38%, p<0.0005). Age was only modestly related to the index, with a decline by 0.017 log unit per decade (R2=10%). Test-retest data for 21 volunteers who completed 7-10 visits yielded standard deviations for the index from 0.04 to 0.17 log unit, with a mean of 0.09 log unit. Between-subject differences in peripheral deviation persisted over two years of longitudinal testing. Peripheral deviation indices were correlated with indices for three other perimetric stimuli used in a subset of 24 volunteers (R2 from 20% to 49%). Between-subject variability in shape of the visual field raises concerns about current clinical visual field indices, and further studies are needed to develop improved indices.

A comparative analysis of the effects of the fixed combination of timolol and dorzolamide versus latanoprost plus timolol on ocular hemodynamics and visual function in patients with primary open-angle glaucoma.

AIMS: The aim of this study was to assess the effects of fixed combination of timolol and dorzolamide and latanoprost plus timolol on retinal, choroidal, and retrobulbar hemodynamics and visual function in primary open-angle glaucoma (OAG) subjects. METHODS: Sixteen (16) OAG patients (age, 63.5 +/- 10.8 years; 9 male) were evaluated in a randomized, crossover, double-blind study design after 4 weeks of treatment of latanoprost with timolol and fixed combination of timolol and dorzolamide. After randomization, 9 right eyes and 7 left eyes were included in the hemodynamic portion of the study. Measurements included: adverse events check, visual acuity, contrast sensitivity, blood pressure, heart rate, intraocular pressure (IOP), and fundus examination. Ocular blood flow was assessed using confocal scanning laser Doppler flowmetry, color Doppler imaging, and scanning laser ophthalmoscopy. RESULTS: Both therapies were effective at lowering IOP, whereas there was no statistically significant difference between latanoprost plus timolol and the fixed combination of timolol and dorzolamide (13.9% and 12.2% reduction, respectively; P = 0.5533). Fixed combination of timolol and dorzolamide significantly increased central retinal artery end diastolic blood flow velocity (P = 0.0168) and lowered resistance to flow (P = 0.0279). Temporal posterior ciliary artery peak systolic and end diastolic velocities were significantly increased with the fixed combination of timolol and dorzolamide (P = 0.0125 and 0.0238, respectively). Latanoprost plus timolol had no significant effects on ocular blood flow during 4 weeks of treatment. There were no statistically significant differences in adverse events, blood pressure, heart rate, visual acuity, contrast sensitivity scanning laser ophthalmoscopy, or Heidelberg Retinal Flowmeter for any treatment period. CONCLUSIONS: Fixed combination of timolol and dorzolamide therapy might increase blood flow in OAG patients while attaining a similar IOP reduction compared to latanoprost plus timolol. Visual function, however, was not different in this short-term comparison between the two treatments.

Contrast sensitivity perimetry data from adults free of eye disease.

This data article contains data referenced in "Individual Differences in the Shape of the Nasal Visual Field" [1]. The data were gathered from volunteers free of eye disease ages 21-85 who were tested with Contrast Sensitivity Perimetry (CSP), which uses a stimulus resistant to effects of defocus and reduced retinal illumination. Some subjects were tested only once or a few times, and others were part of a longitudinal cohort with as many as 10 tests. Parameters from maximum likelihood estimation of psychophysical threshold at each tested location are included in the data file, along with the participant׳s sex, age at time of test, the center of their physiological blind spot, the duration of test, the time of day that the test was begun, and the starting contrast used for the psychophysical staircases.

Imaging Glaucomatous Damage Across the Temporal Raphe.

PURPOSE: To image and analyze anatomical differences at the temporal raphe between normal and glaucomatous eyes using adaptive optics scanning laser ophthalmoscopy (AOSLO) and optical coherence tomography (OCT), and to relate these differences to visual field measurements. METHODS: Nine glaucomatous eyes of 9 patients (age 54-78 years, mean deviation of visual field [MD] -5.03 to -0.20 dB) and 10 normal eyes of 10 controls (age 54-81, MD -1.13 to +1.39 dB) were enrolled. All the participants were imaged in a region that was centered approximately 9° temporal to the fovea. The size of imaging region was at least 10° vertically by 4° horizontally. The raphe gap, defined as the distance between the superior and inferior retinal nerve fiber layer (RNFL) bundles, was measured. A bundle index was computed to quantify the relative reflectivity and density of the nerve fiber bundles. We also measured thickness of the ganglion cell complex (GCC) and RNFL. RESULTS: The raphe gap was larger in glaucomatous eyes than control eyes. Specifically, eight glaucomatous eyes with local averaged field loss no worse than -3.5 dB had larger raphe gaps than all control eyes. The bundle index, GCC thickness, and RNFL thickness were on average reduced in glaucomatous eyes, with the first two showing statistically significant differences between the two groups. CONCLUSIONS: Structural changes in the temporal raphe were observed and quantified even when local functional loss was mild. These techniques open the possibility of using the raphe as a site for glaucoma research and clinical assessment.

Proton therapy for exudative age-related macular degeneration: a randomized, sham-controlled clinical trial.

PURPOSE: To examine the effect of proton beam irradiation on subfoveal choroidal neovascular membranes (CNVM) associated with age-related macular degeneration (AMD).Randomized, prospective, sham-controlled, double-masked treatment trial. METHODS: Thirty-seven subjects with subfoveal CNVM due to AMD were randomly assigned to 16-Gy proton irradiation delivered in two fractions 24 hours apart or to sham control treatment. Recruitment was halted at 37 subjects for ethical reasons regarding randomization to sham treatment when Food and Drug Administration approval of Visudyne was anticipated. RESULTS: Proton irradiation was associated with a trend toward stabilization of visual acuity, but this association did not reach statistical significance. No correlations were found within the fluorescein angiography data, including greatest linear dimension of CNVM total size, area of active leakage, area of associated subretinal hemorrhage, and intensity. CONCLUSIONS: With the acceptance of photodynamic therapy, future studies will require more complex design and larger sample size to determine whether radiation can play either a primary or adjunctive role in treating these lesions.

Choice of Stimulus Range and Size Can Reduce Test-Retest Variability in Glaucomatous Visual Field Defects.

PURPOSE: To develop guidelines for engineering perimetric stimuli to reduce test-retest 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 = 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.

In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy.

We used a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) to image the retina of subjects with non-proliferative 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.

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.

Measuring accurate IOPs: Does correction factor help or hurt?

PURPOSE: To evaluate if using the Ehlers correction factor on the intraocular pressure (IOP) measured using the Goldmann applanation tonometer (GAT) improves its agreement with the PASCAL dynamic contour tonometer (DCT). PATIENTS AND METHODS: A total of 120 eyes of 120 individuals were examined. Participants underwent IOP measurement with both the DCT and the GAT and central corneal thickness measurement. The Ehlers correction factor was applied on the GAT IOP measurements to calculate Ehlers-corrected GAT IOP. The agreement between the DCT and GAT, and DCT and Ehlers-corrected GAT IOP was analyzed. The analyses were repeated by stratifying the data by race. RESULTS: The mean IOP of the GAT, DCT, and the Ehlers-corrected GAT was 15.30, 16.78, and 14.68 mmHg, respectively. The agreement as assessed by Bland-Altman plot for the GAT with the DCT and DCT and Ehlers-corrected GAT IOP was +4.1 to -6.9 and +4.15 to -8.25 mmHg, respectively. The results were similar even when stratifying the data by race. CONCLUSION: Using Ehlers correction factor to account for the effect of corneal parameters on the IOP measured by the GAT worsens the agreement with the DCT. This effect remains even when stratifying the data by race.