Gregory R. Jackson

Inner retinal visual dysfunction is a sensitive marker of non-proliferative diabetic retinopathy.

Aims To determine the effect of diabetes on inner and outer retinal function in persons with diabetes and no clinically detectable retinopathy or with non-proliferative diabetic retinopathy (NPDR). Methods Visual function was assessed in 18 adults with normal retinal health, 23 adults with diabetes and 35 adults with NPDR and normal visual acuity. Contrast sensitivity and frequency doubling technology (FDT) sensitivity were used to assess ganglion cell function. Acuity, dark adaptation, light-adapted visual sensitivity and dark-adapted visual sensitivity were measured to evaluate cone and rod photoreceptor visual function. The presence and severity of diabetic retinopathy was determined by grading of 7-field stereoscopic fundus photographs using the Early Treatment Diabetic Retinopathy Study grading system. Results Participants with NPDR exhibited impairment of all measured visual functions in comparison with the normal participants. Inner retinal function measured by FDT perimetry was the most impaired visual function for patients with NPDR, with 83% of patients exhibiting clinically significant impairment. Rod photoreceptor function was grossly impaired, with almost half of the patients with NPDR exhibiting significantly impaired dark-adapted visual sensitivity. Conclusion Both inner retinal and outer retinal functions exhibited impairment related to NPDR. FDT perimetry and other visual function tests reveal an expanded range of diabetes induced retinal damage even in patients with good visual acuity.

An Integrated Approach to Diabetic Retinopathy Research

This review discusses the pathophysiology of diabetic retinopathy related to direct effects of loss of insulin receptor action and metabolic dysregulation on the retina. The resulting sensory neuropathy can be diagnosed by structural and functional tests in patients with mild nonproliferative diabetic retinopathy. Research teams can collaborate to integrate ocular and systemic factors that impair vision and to design strategies to maintain retinal function in persons with diabetes mellitus. Evolving concepts may lead to inclusion of tests of retinal function in the detection of diabetic retinopathy and neuroprotective strategies to preserve vision for persons with diabetes.

Visual Dysfunction Associated with Diabetic Retinopathy

Diabetic retinopathy is a leading cause of blindness and is commonly viewed as a vascular complication of diabetes mellitus. However, diabetes mellitus causes visual dysfunction before the onset of clinically visible microvascular changes associated with diabetic retinopathy. Thus, viewing diabetic retinopathy more generally as a neurovascular disease may lead to an improved understanding of the mechanisms responsible for vision loss. This article reviews the impact of diabetes mellitus on inner and outer retinal visual and electrophysiologic function and advocates for a multimodal approach to the study of diabetic retinopathy.

Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration

PURPOSE To examine whether slowed rod-mediated dark adaptation (DA) in adults with normal macular health at baseline is associated with the incidence of age-related macular degeneration (AMD) 3 years later. DESIGN Prospective cohort. PARTICIPANTS Adults aged ≥60 years were recruited from primary care ophthalmology clinics. Both eyes were required to be step 1 (normal) on the Age-Related Eye Disease Study 9-step AMD classification system based on color fundus photographs graded by experienced and masked evaluators. METHODS Rod-mediated DA was assessed at baseline in 1 eye after a photobleach using a computerized dark adaptometer with targets centered at 5° on the inferior vertical meridian. Speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept ≥12.3 minutes. Demographic characteristics, best-corrected visual acuity, and smoking status were also assessed. Log-binomial regression was used to calculate unadjusted and adjusted risk ratios (RRs) and associated 95% confidence intervals (CIs) for the association between baseline DA and incident AMD. MAIN OUTCOME MEASURES Presence of AMD at the 3-year follow-up visit for the eye tested for DA at baseline. RESULTS Both baseline and follow-up visits were completed by 325 persons (mean age, 67.8 years). At baseline, 263 participants had normal DA with mean rod-intercept of 9.1 (standard deviation [SD], 1.5), and 62 participants had abnormal DA with mean rod-intercept of 15.1 (SD, 4.0). After adjustment for age and smoking, those with abnormal DA in the tested eye at baseline were approximately 2 times more likely to have AMD in that eye (RR, 1.92; 95% CI, 1.03-3.62) by the time of the follow-up visit, compared with those who had normal DA at baseline. CONCLUSIONS Delayed rod-mediated DA in older adults with normal macular health is associated with incident early AMD 3 years later, and thus is a functional biomarker for early disease. The biological relevance of this test is high, because it assesses translocation of vitamin A derivatives across the retinal pigment epithelium and Bruchs membrane, 2 tissues with prominent age- and AMD-related pathology.

A short-duration dark adaptation protocol for assessment of age-related maculopathy

Dark adaptometry may be a useful diagnostic test and clinical trial endpoint for age-related maculopathy (ARM) because impaired night vision is a hallmark of early ARM. A novel dark adaptometer, the AdaptDx, was evaluated for the detection of ARM. The AdaptDx incorporates a 20-minute protocol optimized for the detection of ARM. ARM patients (N = 17) exhibited substantial dark adaptation impairment compared with normal adults (N = 17). The diagnostic sensitivity was 88% and the specificity was 100%. The diagnostic test characteristics of the AdaptDx are similar to previously reported studies using 60- to 120-minute protocols.

Diagnostic Sensitivity and Specificity of Dark Adaptometry for Detection of Age-Related Macular Degeneration

PURPOSE Difficulty with night vision is a common complaint of patients with age-related macular degeneration (AMD). Consistent with this complaint, dark adaptation (DA) is substantially impaired in these patients. Because of the severity of the deficit, measurement of DA has been suggested as a means for the diagnosis of AMD. Previous methods for measurement of DA were time intensive (>30 minutes), which made them unsuitable for clinical use. This study evaluated a rapid DA test (≤ 6.5 minutes) for the detection of AMD. METHODS Dark adaptation was measured by using the AdaptDx dark adaptometer in two groups: subjects with normal retinal health and subjects with AMD. Subjects were assigned to their group by clinical examination and grading of fundus photographs. Subjects were classified as having DA consistent with normal retinal health (rod intercept ≤ 6.5 minutes) or having dark adaptation consistent with AMD (rod intercept > 6.5 minutes). RESULTS The eligible sample for analysis included 21 normal adults and 127 AMD patients. The rapid test was found to have a diagnostic sensitivity of 90.6% (P < 0.001) and specificity of 90.5% (P < 0.027). Thus, abnormal DA was detected in 115 of 127 AMD patients, and normal DA was found in 19 of 21 normal adults. CONCLUSIONS The high diagnostic sensitivity and specificity compared favorably to long-duration research methods for the measurement of DA, and slit lamp biomicroscopy performed by a retina specialist. These results suggest that a rapid DA test is useful for the detection of AMD.

Associations Between Abnormal Rod-Mediated Dark Adaptation and Health and Functioning in Older Adults With Normal Macular Health

PURPOSE Delayed rod-mediated dark adaptation (DA) is characteristic of early age-related macular degeneration (AMD) and also can be observed in some older adults in normal macular health. We examine cross-sectional associations between rod-mediated DA and risk factors for AMD in older adults in normal macular health. METHODS The sample consisted of adults aged ≥60 years old in normal macular health per grading of fundus photos using an established disease classification system. Rod-mediated DA was measured psychophysically following a photobleach using a computer-automated dark adaptometer with targets centered at 5° on the inferior vertical meridian. The speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept ≥ 12.3 minutes. We assessed several health and functional characteristics that the literature has suggested increase AMD risk (e.g., smoking, alcohol use, inflammatory markers, apolipoproteins, low luminance visual acuity, chronic medical conditions, body mass, family history). RESULTS Among 381 participants (mean age, 68.5 years; SD, 5.5), 78% had normal and 22% had abnormal DA, with the prevalence of abnormal DA increasing with age. After age-adjustment, abnormal DA was associated with increased odds of elevated C-reactive protein (CRP), heavy use of or abstention from alcohol, high blood pressure, and drop in visual acuity under mesopic conditions. CONCLUSIONS Despite having normal macular health according to accepted definitions of AMD presence, approximately one-quarter of older adults recruited from primary eye care clinics had abnormal DA, which was associated with known risk factors for AMD, including elevated CRP.

Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health

Abstract Purpose: To compare the ability of several visual functional tests in terms of the strength of their associations with the earliest phases of age-related macular degeneration (AMD), which bears on their potential to serve as functional endpoints in evaluating treatments for early AMD and prevention strategies. Materials and methods: Eyes from adults ≥60 years old were identified as being in normal macular health or in the earliest stages of AMD (steps 2, 3 or 4) through grading of color stereo-fundus photos by an experienced grader masked to all other study variables who used the 9-step Age-Related Eye Disease Study (AREDS) classification system for AMD severity. Visual function was assessed using the following tests: best-corrected visual acuity, low luminance visual acuity, spatial contrast sensitivity, macular cone-mediated light sensitivity and rod-mediated dark adaptation. Results: A total of 1260 eyes were tested from 640 participants; 1007 eyes were in normal macular health (defined as step 1 in AREDS system) and 253 eyes had early AMD (defined as steps 2, 3 or 4). Adjusting for age and gender, early AMD eyes had two times the odds of having delayed rod-mediated dark adaptation than eyes in normal macular health (p = 0.0019). Visual acuity, low luminance acuity, spatial contrast sensitivity and macular light sensitivity did not differ between normal eyes and early AMD eyes. Conclusions: Eyes in the earliest phases of AMD were two times more likely to have delayed rod-mediated dark adaptation, as assessed by the rod-intercept, as compared to older eyes in normal macular health, whereas there was no difference in early AMD versus normal eyes in tests of visual acuity, low luminance acuity, macular light sensitivity and spatial contrast sensitivity.

Aging and feature search : The effect of search area

The preattentive system involves the rapid parallel processing of visual information in the visual scene so that attention can be directed to mean ingful objects and locations in the environment. This study used the feature search methodology to examine whether there are aging-related deficits in parallel-processing capabilities when older adults are required to visually search a large area of the visual field. Like young subjects, older subjects displayed flat, near-zero slopes for the Reaction Time 2 Set Size function when searching over a broad area (30 radius) of the visual field, implying parallel processing of the visual display. These same older subjects exhibited impairment in another task, also dependent on parallel processing, performed over the same broad field area; this task, called the useful field of view test, has more complex task demands. Results imply that aging-related breakdowns of parallel pro cessing over a large visual field area are not likely to emerge when required responses are simple, there is only one task to perform, and there is no limitation on visual inspection time.The preattentive system involves the rapid parallel processing of visual information in the visual scene so that attention can be directed to meaningful objects and locations in the environment. This study used the feature search methodology to examine whether there are aging-related deficits in parallel-processing capabilities when older adults are required to visually search a large area of the visual field. Like young subjects, older subjects displayed flat, near-zero slopes for the Reaction Time x Set Size function when searching over a broad area (30 degrees radius) of the visual field, implying parallel processing of the visual display. These same older subjects exhibited impairment in another task, also dependent on parallel processing, performed over the same broad field area; this task, called the useful field of view test, has more complex task demands. Results imply that aging-related breakdowns of parallel processing over a large visual field area are not likely to emerge when required responses are simple, there is only one task to perform, and there is no limitation on visual inspection time.

Multimodal Characterization of Proliferative Diabetic Retinopathy Reveals Alterations in Outer Retinal Function and Structure

PURPOSE To identify changes in retinal function and structure in persons with proliferative diabetic retinopathy (PDR), including the effects of panretinal photocoagulation (PRP). DESIGN Cross-sectional study. PARTICIPANTS Thirty adults who underwent PRP for PDR, 15 adults with untreated PDR, and 15 age-matched controls. METHODS Contrast sensitivity, frequency doubling perimetry (FDP), Humphrey visual fields, photostress recovery, and dark adaptation were assessed. Fundus photography and macular spectral-domain optical coherence tomography (SD OCT) were performed. To quantify retinal layer thicknesses, SD OCT scans were segmented semiautomatically. MAIN OUTCOME MEASURES Visual function measures were compared among patients with PDR and PRP, untreated patients with PDR, and controls. Mean retinal layer thicknesses were compared between groups. Correlation analyses were performed to evaluate associations between visual function measures and retinal layer thicknesses. RESULTS A significant reduction of FDP mean deviation (MD) was exhibited in PRP-treated patients with PDR (MD ± standard deviation, -8.20±5.76 dB; P < 0.0001) and untreated patients (-5.48±4.48 dB; P < 0.0001) relative to controls (1.07±2.50 dB). Reduced log contrast sensitivity compared with controls (1.80±0.14) also was observed in both PRP-treated patients (1.42±0.17; P < 0.0001) and untreated patients (1.56±0.20; P = 0.001) with PDR. Compared with controls, patients treated with PRP demonstrated increased photostress recovery time (151.02±104.43 vs. 70.64±47.14 seconds; P = 0.001) and dark adaptation speed (12.80±5.15 vs. 9.74±2.56 minutes; P = 0.022). Patients who underwent PRP had diffusely thickened nerve fiber layers (P = 0.024) and diffusely thinned retinal pigment epithelium (RPE) layers (P = 0.009) versus controls. Untreated patients with PDR also had diffusely thinned RPE layers (P = 0.031) compared with controls. CONCLUSIONS Patients with untreated PDR exhibited inner retinal dysfunction, as evidenced by reduced contrast sensitivity and FDP performance, accompanied by alterations in inner and outer retinal structure. Patients who underwent PRP had more profound changes in outer retinal structure and function. Distinguishing the effects of PDR and PRP may guide the development of restorative vision therapies for patients with advanced diabetic retinopathy.