Ann E.. Elsner

We demonstrate a potential vision tester (PVT), designed to improve the accuracy of visual acuity (VA) measurements in older eyes with exudative retinal disease quantified by optical coherence tomography (OCT). Key features include a high-resolution visual display presented in Maxwellian view, a 3 mm pupil to limit wavefront (WF) aberrations, a selected fixed cylinder lens to correct astigmatism, and a tunable lens to correct sphere. An external Hartmann-Shack-based autorefractor provided objective sphere and cylinder corrections. Subjective values of the sphere were obtained by the patient adjusting the tunable lens. VA was measured using four alternative forced choice for a single black-on-white E stimulus. In patients with exudative retinal disease, VAs did not differ when using the objective vs. subjective sphere values. The significant difference in the myopic direction for two subjective settings (-0.093, -0.28 D) vs. one objective setting (0.0 D) was too small to cause a difference in VA for this patient group, supporting the use of an autorefractor for VA measurements.

We sought to improve the measurement of visual acuity (VA) by reducing the effect of unwanted optical artifacts in patients with retinal disease. We evaluated the effects of age and of inherent and induced aberrations on VA for controls and patients with changes to the posterior segment, anterior segment, or both. We tested VA in 30 controls and 17 patients, using Maxwellian view and a 3 mm pupil. This method reduces wavefront aberrations and allows high spatial frequency information to be transmitted at a constant retinal illuminance. We reduced glare, crowding, and fixation errors by projecting a single letter E in a small field size. We corrected only defocus, then determined the extent to which VA and standard deviation (SD) were influenced by age and inherent wavefront aberrations (astigmatism, spherical aberration, and root mean square error higher order aberrations (RMSHO)), as well as by induced aberrations (spherical aberrations and coma). Optical coherence tomography (OCT) provided central macular thickness (CMT), which was compared to wavefront and VA results to determine the effect of retinal status. The use of Maxwellian view and a 3 mm pupil reduced aberrations, but the association between VA and inherent astigmatism ( p = 0.011) was significant for controls, although not for patients. For controls, RMSHO significantly increased with age ( p = 0.014), despite no impact on VA. Induced aberrations, which were as large as with 5 mm pupils, significantly worsened mean VA in controls ( p < 0.001) and patients ( p < 0.001), more for positive spherical aberrations than negative. Using Maxwellian view and a 3 mm pupil reduced optical aberrations and their effects on VA, important in managing patients with retinal disease. Only residual astigmatism was related to poorer VA.

We demonstrate a potential vision tester (PVT) designed to study and improve the accuracy of visual acuity (VA) measurements in the aging eye. Key features include a high-resolution visual display presented in Maxwellian view, a 3 mm pupil to limit wavefront (WF) aberrations, a Hartmann Shack wavefront sensor to quantify the ocular aberrations, and a deformable mirror to correct optical aberrations. VA was measured using four alternative forced choices for a single black-on-white E stimulus in each trial, with three different levels of correction for the ocular aberrations. For normally sighted subjects, VA was not significantly better when higher-order aberrations beyond second order were corrected.

SIGNIFICANCE: Visual acuity (VA) depends on many factors. When the goal is to assess retinal health rather than performance, then using a 3‐mm pupil reduces unwanted wavefront aberrations. The axis of astigmatism can still potentially change with age. PURPOSE: When VA measurements are intended to quantify the status of the retina, extraneous optical aberrations can make the measured VA worse and introduce variability, particularly in aging eyes. Our study quantifies wavefront aberrations for a 3‐mm pupil, which is similar to the theoretical optical size for best VA, versus a 5‐mm pupil. METHODS: The wavefront aberrations of normally sighted adults (N = 39; age, 41.9 ± 16.3 years) were measured for a 3‐ and 5‐mm pupil setting without pupil dilation, using a commercially available and semiautomatic instrument (Pentacam AXL WAV; Oculus Optikgeraete GmbH, Wetzlar, Germany). The mean wavefront errors from the average of three measurements with three samples each were computed for each Zernike term orders 1 to 6 and correlated with age. The difference of measurement 1 and measurement 2 provided the test‐retest values. RESULTS: Each 3‐mm pupil measurements had a reduced average aberration for all 26 aberrations Zernike values, and 21 of 26 were statistically significant (pF = 54.625, p60 than <40 years old (p=0.05). CONCLUSIONS: The findings of this study indicate that measurements of VA to assess retinal health could be made less dependent on unrelated and unwanted anterior segment factors by using a 3‐mm pupil, because the wavefront aberrations for a 3‐mm pupil were less than those for a 5‐mm pupil. The change with age in vertical astigmatism more than oblique is consistent with the expected increase in proportion of against‐the‐rule astigmatism.

Purpose: Visual acuity (VA) is a primary outcome measure that defines the success of clinical interventions for retinal diseases such as age‐related macular degeneration (AMD) or diabetic macular oedema (DME). These conditions can lead to the presence of subretinal fluid, causing substantial photoreceptor layer elevation. Hyperopic defocus then occurs, affecting the VA measurements. In this study, we simulated the induced hyperopic shift for real‐world values of photoreceptor layer elevation and measured the effect on VA measurements. Methods: To simulate the hyperopic shift, we used a four‐surface eye model. To measure the effect of defocus on VA, normally sighted adults ( N = 44, mean [SD] age = 32 [13.0] year, range: 21–71 year) performed four test conditions, that is, defocus of 0.00, +0.75, +1.50 and +2.25 D. For each subject, mean VA and SD obtained from a cumulative normal fit to the VA data provided the coefficient of variation (CV) and 95% confidence interval (CI). Results: Refractive error induced by photoreceptor layer elevation was maximum for hyperopic error conditions, followed by emmetropic and myopic refractive error conditions. The 76% threshold VA worsened with increasing defocus conditions. The 95% CI was significantly larger for +0.75, +1.50 and +2.25 D defocus compared to no defocus ( p = 0.04, 0.02 and 0.01, respectively). The CI for the +2.25 D defocus condition was larger (3–10 letters) compared with no defocus (3–6 letters). Conclusions: Photoreceptor layer elevation causes a hyperopic shift sufficient for clinically meaningful changes: worse VA and more variable measurements.

SIGNIFICANCE: Suspected clinically significant macular edema (SCSME) from exudates differed among ethnic groups in our underserved population. African American and Asian subjects had higher prevalence than Hispanics and non‐Hispanic Caucasians, from the same clinics. Men had higher prevalence than women. Highly elevated blood glucose was frequent and associated with SCSME. PURPOSE: We investigated the association between the presence of SCSME from exudates and hemoglobin A1c (HbA1c), as well as demographic factors such as age, sex, and ethnic group. Our population was underserved diabetic patients from the same geographic locations. Ethnic groups were White Hispanic, non‐Hispanic Caucasian, African American, and Asian, with a high proportion of underrepresented minorities. METHODS: In a diabetic retinopathy screening study at four community clinics in Alameda County, California, nonmydriatic 45° color fundus images were collected from underserved diabetic subjects following the EyePACS imaging protocol. Images were analyzed for SCSME from exudates by two certified graders. Logistic regression assessed the association between SCSME from exudates and age, sex, ethnic group, and HbA1c. RESULTS: Of 1997 subjects, 147 (7.36%) had SCSME from exudates. The mean ± standard deviation age was 53.4 ± 10.5 years. The mean ± standard deviation HbA1c level was 8.26 ± 2.04. Logistic regression analysis indicated a significant association between presence of SCSME from exudates and HbA1c levels (p Hispanics), sex (male > female), and HbA1c level were strong indicators for identifying who is at increased risk of developing SCSME from exudates.

We demonstrate a free-space, trolley-mounted potential vision tester (PVT), designed to study and improve the accuracy of visual acuity (VA) measurements in the aging eye. Key features include a high-resolution visual display presented in Maxwellian view, a 3 mm pupil to limit wavefront (WF) aberrations, and a moderate cost deformable mirror to induce or correct higher order optical aberrations. The visual display supported accurate measurement of visual acuities down to 20/5. The moderate cost, piezo deformable mirror induced seven nominal aberrations, calibrated as 0, -0.32, -0.23, + 0.27, and +0.39 microns spherical aberration; + 0.49 microns Y coma; and -0.51 microns X coma. A custom Hartmann Shack (HS) calibration (HSc) system demonstrated that induced aberrations were repeatable and stable. A Badal optometer provided the coarse focus. WF aberrations were measured for five normal subjects with a commercially available HS device (HSP) (OCULUS Pentacam AXL Wave), providing estimates of WF errors for 3 mm and other pupil sizes. VA was measured using four alternative forced-choice for a single black on white E stimulus in each trial. Using the method of constant stimuli yielded robust standard deviation measurements. The 50% fit for VA plotted against induced aberration resulted in linear functions for each subject for the range of our positive and negative spherical aberration data. Subjects differed, but higher order terms were unnecessary to describe data across spherical aberrations.

SIGNIFICANCE: Patient‐based research plays a key role in probing basic visual mechanisms. Less‐well recognized is the role of patient‐based retinal imaging and visual function studies in elucidating disease mechanisms, which are accelerated by advances in imaging and function techniques and are most powerful when combined with the results from histology and animal models. A patient's visual complaints can be one key to patient management, but human data are also key to understanding disease mechanisms. Unfortunately, pathological changes can be difficult to detect. Before advanced retinal imaging, the measurement of visual function indicated the presence of pathological changes that were undetectable with existing clinical examination. Over the past few decades, advances in retinal imaging have increasingly revealed the unseen. This has led to great strides in the management of many diseases, particularly diabetic retinopathy and macular edema, and age‐related macular degeneration. It is likely widely accepted that patient‐based research, as in clinical trials, led to such positive outcomes. Both visual function measures and advanced retinal imaging have clearly demonstrated differences among retinal diseases. Contrary to initial thinking, sight‐threatening damage in diabetes occurs to the outer retina and not only to the inner retina. This has been clearly indicated in patient results but has only gradually entered the clinical classifications and understanding of disease etiology. There is strikingly different pathophysiology for age‐related macular degeneration compared with photoreceptor and retinal pigment epithelial genetic defects, yet research models and even some treatments confuse these. It is important to recognize the role that patient‐based research plays in probing basic visual mechanisms and elucidating disease mechanisms, combining these findings with the concepts from histology and animal models. Thus, this article combines sample instrumentation from my laboratory and progress in the fields of retinal imaging and visual function.

This is the editorial that is part of our topic, The Neural Economy Hypothesis: Changes with Aging and Disease to Cones and other Central Nervous System Visual Neurons

Purpose: Cones in diabetic patients are at risk due to metabolic and vascular changes. By imaging retinal vessel modeling at high magnification, we reduced its impact on cone distribution measurements. The retinal vessel images and retinal thickness measurements provided information about cone microenvironment.Methods: We compared cone data in 10 diabetic subjects (28–78 yr) to our published norms from 36 younger and 10 older controls. All subjects were consented and tested in a manner approved by the Indiana University Institutional Review Board, which adhered to the Declaration of Helsinki. Custom adaptive optics scanning laser ophthalmoscopy (AOSLO) was used to image cones and retinal microcirculation. We counted cones in a montage of foveal and temporal retina, using four non-contiguous samples within 0.9–7 deg that were selected for best visibility of cones and least pathology. The data were fit with a two parameter exponential model: ln(cone density) = a ^* microns eccentricity + b. These results were compared to retinal thickness measurements from SDOCT.Results: Diabetic cone maps were more variable than in controls and included patches, or unusually bright and dark cones, centrally and more peripherally. Model parameters and total cones within the central 14 deg of the macula differed across diabetic patients. Total cones fell into two groups: similar to normal for 5 vs. less than normal for 2 of 2 younger diabetic subjects and 3 older subjects, low but not outside the confidence limits. Diabetic subjects had all retinal vascular remodeling to varying degrees: microaneurysms; capillary thickening, thinning, or bends; and vessel elongation including capillary loops, tangles, and collaterals. Yet SD-OCT showed that no diabetic subject had a Total Retinal Thickness in any quadrant that fell outside the confidence limits for controls.Conclusions: AOSLO images pinpointed widespread retinal vascular remodeling in all diabetic eyes, but the SDOCT showed no increased retinal thickness. Cone reflectivity changes were found in all diabetic patients, but significantly low cone density in only some. These results are consistent with early changes to neural, glial, or vascular components of the retinal without significant retinal thickening due to exudation.