Abstract

Dark adaptation (DA) refers to the slow recovery of visual sensitivity in darkness following exposure to intense or prolonged illumination, which bleaches a significant amount of the rhodopsin. This natural process also offers an opportunity to understand cellular function in the outer retina and evaluate for presence of disease. How our eyes adapt to darkness can be a key indicator of retinal health, which can be altered in the presence of certain diseases, such as age-related macular degeneration (AMD). A specific focus on clinical aspects of DA measurement and its significance to furthering our understanding of AMD has revealed essential findings underlying the pathobiology of the disease. The process of dark adaptation involves phototransduction taking place mainly between the photoreceptor outer segments and the retinal pigment epithelial (RPE) layer. DA occurs over a large range of luminance and is modulated by both cone and rod photoreceptors. In the photopic ranges, rods are saturated and cone cells adapt to the high luminance levels. However, under scotopic ranges, cones are unable to respond to the dim luminance and rods modulate the responses to lower levels of light as they can respond to even a single photon. Since the cone visual cycle is also based on the Muller cells, measuring the impairment in rod-based dark adaptation is thought to be particularly relevant to diseases such as AMD, which involves both photoreceptors and RPE. Dark adaptation parameters are metrics derived from curve-fitting dark adaptation sensitivities over time and can represent specific cellular function. Parameters such as the cone-rod break (CRB) and rod intercept time (RIT) are particularly sensitive to changes in the outer retina. There is some structural and functional continuum between normal aging and the AMD pathology. Many studies have shown an increase of the rod intercept time (RIT), i.e., delays in rod-mediated DA in AMD patients with increasing disease severity determined by increased drusen grade, pigment changes and the presence of subretinal drusenoid deposits (SDD) and association with certain morphological features in the peripheral retina. Specifications of spatial testing location, repeatability of the testing, ease and availability of the testing device in clinical settings, and test duration in elderly population are also important. We provide a detailed overview in light of all these factors.

Highlights

  • Dark adaptation (DA) refers to the capability to see in low light or darkness after exposure to bright light

  • Pathologic changes to any of these cell layers or inter-cellular spaces have the potential to impact dark adaptation [3]. Monogenic diseases affecting these structures including the anatomy of Bruch’s membrane (BrM) (Sorsby Fundus Dystrophy [SFD], Pseudoxanthoma elasticum [pseudoxanthoma elasticum (PXE)]), the function of enzymes in the retinal pigment epithelial (RPE) (RPE65-related Retinitis pigmentosa, Late-onset retinal degeneration [late-onset retinal degeneration (LORD)]), or rod structure (RHO-associated Retinitis pigmentosa), all cause delays in dark adaptation [26,58,59,65–68]

  • Tahir et al (2018) [63] reported that the earliest DA abnormality observed in age-related macular degeneration (AMD) was a reduction in the steepness of rod-recovery slope and delays in the time to the cone-rod break was not observed until more advanced disease

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Summary

Introduction

Dark adaptation (DA) refers to the capability to see in low light or darkness after exposure to bright light This natural process offers an opportunity to understand the functioning of cellular function in the outer retina and evaluate for presence of disease. Pupil size is one of the important considerations when measuring dark adaptation [2,5,11] (its role is described in subsequent sections), we are more interested in the gradual increase in the visual sensitivity than the pupillary response when studying. In the vision science literature in general, dark adaptation is defined as the slow recovery of the sensitivity of the visual system after exposure to very bright light followed by a rapid (sudden) transition to darkness, usually with a controlled pupil size [5]

Characteristics of Cone and Rod Mediated Vision
Phototransduction
Summarizing the
Importance of DA Measurement
Overview of DA Measurement Procedure
Measurement Conditions & How They Affect DA Response
Physiological Factors Affecting DA Response
DA Measurement Instruments
Retinal Pathology and Dark Adaptation
Function
Functional Deficits in AMD
Association of DA Dysfunction with AMD Severity including Reticular Pseudodrusen
Functional Phenotypes and Spatial Effect across the Macula
Structure-Function Correlation Using Multimodal Imaging
Dark Adaptation as an Early Marker in Eyes at Risk of AMD–Transition from Health to Disease
Longitudinal Comparison of Morphological and Psychophysical Disease Progression
Role of Genetic and Environmental Factors in Dark Adaptation
Relevance to Daily Life–Patient-Reported Outcome Measures
A Note Regarding the Choice of Instrument and DA Testing Protocol Utilized
Use of Dark Adaptation as a Screening Tool for AMD
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