Elsevier

Survey of Ophthalmology

Volume 54, Issue 2, March–April 2009, Pages 167-210
Survey of Ophthalmology

Major Review
Psychophysical Function in Age-related Maculopathy

https://doi.org/10.1016/j.survophthal.2008.12.003Get rights and content

Abstract

Age-related macular degeneration (AMD), the late stage of age-related maculopathy (ARM), is the leading cause of blind registration in developed countries. The visual loss in AMD occurs due to dysfunction and death of photoreceptors (rods and cones) secondary to an atrophic or a neovascular event. The psychophysical tests of vision, which depend on the functional status of the photoreceptors, may detect subtle alterations in the macula before morphological fundus changes are apparent ophthalmoscopically, and before traditional measures of visual acuity exhibit deterioration, and may be a useful tool for assessing and monitoring patients with ARM. Furthermore, worsening of these visual functions over time may reflect disease progression, and some of these, alone or in combination with other parameters, may act as a prognostic indicator for identifying eyes at risk for developing neovascular AMD. Lastly, psychophysical tests often correlate with subjective and relatively undefined symptoms in patients with early ARM, and may reflect limitation of daily activities for ARM patients. However, clinical studies investigating psychophysical function have largely been cross-sectional in nature, with small sample sizes, and lack consistency in terms of the grading and classification of ARM. This article aims to comprehensively review the literature germane to psychophysical tests in ARM, and to furnish the reader with an insight into this complex area of research.

Section snippets

I. Introduction

Age-related macular degeneration (AMD), the advanced stage of age-related maculopathy (ARM), is a degenerative condition of the macula characterized by dysfunction and death of photoreceptors secondary to an atrophic (geographic atrophy, GA) and/or a neovascular (choroidal neovascularization, CNV) event. Currently, AMD is the leading cause of blind registration in the developed world,73, 113, 119 with CNV accounting for 80–90% of these cases.149, 196

In the future, the prevalence and incidence

II. Anatomy of the Macula

The macula lutea refers to a region of the posterior retina that measures approximately 5.5 mm in diameter, and is exquisitely specialized for central and color vision.289 The macula differs from the rest of the retina by the presence of an exceptionally high density of neural elements and restricted blood supply.247 Furthermore, one of the unique feature of the primate macula is the presence of xanthophylls, lutein (L) and zeaxanthin (Z), which provide its eponymous yellow color. Together,

III. Age-related Maculopathy: Definition

In this review article, we have, where possible and in the context of the grading system used in the cited studies, adopted the International Classification and Grading System for Age-Related Maculopathy and Age-Related Macular Degeneration.30 According to this classification, early ARM is defined as the presence of soft drusen (≥63 μm) and/or areas of RPE changes in the form of hyperpigmentation and/or hypopigmentation. The late stages of ARM, also known as AMD, include dry AMD (GA of the RPE

IV. Age-related Maculopathy: Why the Macula?

The vulnerability of the macula to degenerative changes possibly reflects the anatomical and physiological features that render this region of the retina uniquely suitable for central vision.247 The macula has a very high density of photoreceptors, which consume higher levels of oxygen than any other cell type in the body. However, and paradoxically, these cells have a restricted blood supply from the retina, and depend on the oxygen supplied by the choriocapillaris.201 The blood flow within

V. Visual Psychophysics

Visual psychophysics (psycho = perception, and physics = physical nature of the stimulus) is the science of studying visual perception and sensation by determining the relationship between controlled visual stimuli and a subject's response.46 Assuming that the retina and brain are solely responsible for transforming light into vision, psychophysical studies provide valuable information about the functional status of visual processes. Furthermore, psychophysical findings are complementary to

VI. Spatial Vision in Age-related Maculopathy

Spatial vision is the field of psychology that examines how the patterns of light on the retina are interpreted by the visual system (Ferwerda 2006; http://www.graphics.cornell.edu), and is further subdivided into VA (high-contrast VA), low-contrast VA, hyperacuity, reading speed, and contrast sensitivity.

VII. Temporal Function

Temporal function represents the response of an eye to a flickering stimulus, and can also be assessed for non-periodic stimuli. For instance, temporal integration can be assessed by measuring the period of time over which response summation occurs, and temporal resolution can be assessed with two-pulse discrimination. In this context, temporal summation refers to the eye's ability to sum the effects of individual quanta of light over time, and it only occurs within a certain period of time

VIII. Visual Adaptation in Age-related Maculopathy

Visual adaptation refers to a remarkable ability of the human eye to function over a wide range of luminances (greater than 10 log units), and is achieved through a coordinated action of mechanical, photochemical, and neural processes in the visual system.178 The integrity of these visual processes can be assessed using psychophysical tests such as dark adaptation (DA) of rods and cones and the glare recovery test.

A. Definition and basic principle

The term perimetry is used almost interchangeably with visual field testing, and dates back to fifth century B.C.E. when Hippocrates first described a hemianopic defect.46 This psychophysical test measures the visual function of the eye at topographically defined loci in the visual field. Perimetry is based on the concept of visual threshold testing, and constitutes an integral component for the diagnosis and management of various eye diseases.

The visual field (VF) is that portion of the

A. Definition and basic principle

Color vision (CV) represents the ability to discriminate between stimuli, which differ in spectral composition, regardless of other dimensions such as intensity. External objects reflect a variety of wavelengths and the observer constructs a color percept based on the photoreceptor responses to the wavelength distribution and spatial variables.310 Impairment of CV may be one of the earliest detectable changes in the visual process in the presence of retinal disease.

The three types of cone

XI. Correlation Between Histopathologic Changes and Psychophysical Function

Age-related maculopathy is a heterogeneous group of disorders that affects the RPE, Bruch's membrane, and choriocapillaris (the RPE/Bruch's membrane complex), and involves pathological changes superimposed on the aging process.126, 271 The earliest histopathologic feature of ARM is the accumulation of abnormal material within Bruch's membrane, which may be in the form of discrete or diffuse deposits.127, 271

The abnormal material within Bruch's membrane, if rich in neutral lipids, creates a

XII. Discussion

In this review article, we have critically appraised the evidence for subtle deficits in psychophysical function, such as spatial and temporal vision, adaptation mechanisms, VF sensitivity, chromatic function, in the prodromal phases of ARM. We have found consistent evidence of deficits in many of the complex psychophysical measures of the physiological status of the photoreceptors and of the RPE. These visual functions are affected early in the disease process of ARM before high contrast VA is

XIII. Conclusion and Future Directions

Based on this review article, it is clear that several aspects of visual function are adversely affected in early ARM, before a change in distance visual acuity is detectable. In addition, psychophysical function has been linked with high-risk features and subsequent development of neovascular AMD, suggesting that some of these functions (such as S-cone sensitivity, flicker sensitivity, DA, color-match area, and PSRT) may be of prognostic value in identifying eyes at risk for developing

XIV. Method of Literature Search

References for this review article were identified through a systematic search of the Medline database using PubMed Web site (1959 to 2007). Further articles, abstracts, and textbook references, generated from reviewing the bibliographies of the initial search, were retrieved and included. Additional sources (such as non-peer reviewed articles, Web sites, and book chapters) were included based on the relevance to subject; however, such material was cited in the text rather than in the reference

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    The authors reported no proprietary or commercial interest in any prouduct mentioned or concept discussed in this article. The authors acknowledge Ms. Leigh Anne Maddock for the invaluable assistance in editing the tables and creating figures for this article.

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