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The main aim of the paper is to discuss current knowledge on how Age Related Macular Degeneration (AMD) affects Dark Adaptation (DA). The paper is divided into three parts. Firstly, we outline some of the molecular mechanisms that control DA. Secondly, we review the psychophysical issues and the corresponding analytical techniques. Finally, we characterise the link between slowed DA and the morphological abnormalities in early AMD. Historically, DA has been regarded as too cumbersome for widespread clinical application. Yet the technique is extremely useful; it is widely accepted that the psychophysically obtained slope of the second rod-mediated phase of the dark adaptation function is an accurate assay of photoreceptor pigment regeneration kinetics. Technological developments have prompted new ways of generating the DA curve, but analytical problems remain. A simple potential solution to these, based on the application of a novel fast mathematical algorithm, is presented. This allows the calculation of the parameters of the DA curve in real time. Improving current management of AMD will depend on identifying a satisfactory endpoint for evaluating future therapeutic strategies. This must be implemented before the onset of severe disease. Morphological changes progress too slowly to act as a satisfactory endpoint for new therapies whereas functional changes, such as those seen in DA, may have more potential in this regard. It is important to recognise, however, that the functional changes are not confined to rods and that building a mathematical model of the DA curve enables the separation of rod and cone dysfunction and allows more versatility in terms of the range of disease severity that can be monitored. Examples are presented that show how analysing the DA curve into its constituent components can improve our understanding of the morphological changes in early AMD.

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[This corrects the article DOI: 10.3389/fnins.2011.00084.].

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M-cone stimulation induces a pupil constriction to stimulus offset, whereas, with L cones, the pupil responds conventionally with a constriction to onset. To test the possibility that this paradox is linked to the ${\rm L}{:}{\rm M}$L:M ratio, we measured the strength of the effect by injecting a variable amount of positive or negative luminance contamination on either side of M-cone isolation and identifying a balance point at which the pupil responded equally to onset and offset. Nineteen individuals were recruited. In observers with low ${\rm L}{:}{\rm M}$L:M ratio, the paradoxical effect was weak. There was a significant relationship (${{r}^2} = {0.561}$r2=0.561) between the balance point and ${\rm L}{:}{\rm M}$L:M ratio. The effect is likely to be linked to strong inhibitory signals associated with cone-opponent pathways.

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Purpose: The purpose of this paper is to describe the extent to which scotopic and photopic measures of visual function predict color fundus photograph (CFP) and fundus autofluorescence (FAF) changes in early and intermediate nonexudative AMD. Methods: Sixty-nine observers were recruited: 56 AMD patients (mean age, 73 ± 12.98 years) and 13 controls (mean age, 67.77 ± 9.72 years). A nonmydriatic retinal camera was used to obtain stereo fundus photographs and FAF images were recorded with a cSLO Heidelberg Spectralis HRA+OCT. Visual acuity (VA) was measured using an Early Treatment of Diabetic Retinopathy Study chart. Contrast sensitivity (CS) was assessed with a Pelli-Robson chart. Dark adaptation (DA) curves were recorded at 3° eccentricity using a PC-based technique. Analysis of these curves yielded five parameters: cone threshold (CT), cone time constant (CC), cone-rod break (α), slope of the second rod component (S2), and rod-rod break (ß). Results: Both cone and rod sensitivity recovery were grossly abnormal in the patients. The rod recovery slope (S2) most accurately predicted the fundus photograph-based grade and the FAF classification (ρ = 0.61 and ρ = 0.60, respectively; both P < 0.0001). CS showed a strong association with FAF (ρ = 0.50, P < 0.0001) and with fundus photograph-based grade (ρ = 0.38, P < 0.002). There was no correlation between VA and either imaging method. Conclusions: Dynamic, rod-based measures most accurately reflect the severity of early AMD. Although less specific to AMD than DA changes, static photopic abnormalities such as CS also correspond with morphologic changes. Assessment of function in early AMD should include dynamic rod- and cone-mediated measurements of sensitivity recovery.

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Purpose: The recovery of visual sensitivity after a photobleach in early AMD is slowed in rods but cones also may be abnormal. The purpose of this article was to test different stimulus locations to investigate cone function and its relation to rod abnormalities. Methods: Stimuli were presented at two locations, 3.0° and 5.5°, in the inferior visual field. Post photobleach dark adaptation (DA) curves from 50 early-AMD patients were compared with those from 15 healthy controls of similar age. Curves were characterized in terms of four parameters: ct, cone threshold; α, the transition point from cone to rod function; S2, the slope of the second rod-mediated component; and ß, the transition from the second to the third rod-mediated component. Results: There were strong location effects for the healthy group and the AMD group. Cone threshold was higher for the outer compared with the inner stimulus (P = 0.001), S2 was steeper for outer compared with inner (P < 0.001), α was shorter for outer (P = 0.004), and ß was shorter for outer than inner (P = 0.002). The high variance in the patient data, particularly for α and ß, explained the absence of a group*location interaction in the statistics. Conclusions: The data provide a novel perspective on abnormal cone- and rod-sensitivity recovery in early dry AMD. The comparison of pairs of DA curves from different locations highlights the involvement of cones in the underlying pathology of AMD. Dynamic measures of visual function are particularly sensitive to early AMD.

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PURPOSE: The rate of rod sensitivity recovery following a photobleach is a basic measure of the integrity of the outer retina. Rods are selectively impaired in aging and many disorders of the retina, notably Age-Related Macular Degeneration (AMD). It is not known for certain whether the age-related deficit is a pan-retinal effect or if there are localised regions of impaired rod function. To address this important issue a dual arc stimulus was developed that samples sensitivity recovery in two retinal locations. METHODS: Arc-shaped stimuli were presented on a black CRT screen at two locations, in the inferior visual field. Following a bleach, which was localised to the stimuli, recovery of sensitivity was measured using a modified method of adjustment technique. Neutral density filters were used to extend the luminance range of the CRT. Sensitivity recovery functions were fitted by non-linear regression to a seven-parameter model. RESULTS: Pairs of sensitivity recovery functions were generated from the stimuli. The cone phases of these functions were identical. The slopes of the S2 sections of the curves were steeper for the outer stimuli for both young (p < 0.001) and older (p = 0.003) observers. The difference between the two was the same for the two groups. The α point was reached slightly earlier for the young observers and with the outer stimulus but neither of these effects reached statistical significance. The ß point occurred earlier for the outer stimuli and this effect was statistically significant only for the older group. CONCLUSIONS: The method places minimal demands on observers. The fact that rod sensitivity recovery is slowed in the older normal eye to the same extent in the two locations suggests that this deficit may be uniform across the retina. As there are localised losses in scotopic function in AMD, the technique is ideally suited to distinguishing impaired recovery dynamics due to normal ageing from those caused by disease.

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UNLABELLED: Most work on visual prostheses has centered on developing retinal or cortical devices. However, when retinal implants are not feasible, neuroprostheses could be implanted in the lateral geniculate nucleus (LGN) of the thalamus, the intermediate relay station of visual information from the retina to the visual cortex (V1). The objective of the present study was to determine the types of artificial stimuli that when delivered to the visual thalamus can generate reliable responses of the cortical neurons similar to those obtained when the eye perceives a visual image. Visual stimuli {S(i)} were presented to one eye of an experimental animal and both, the thalamic {RTh(i)} and cortical responses {RV1(i)} to such stimuli were recorded. Electrical patterns {RTh(i)*} resembling {RTh(i)} were then injected into the visual thalamus to obtain cortical responses {RV1(i)*} similar to {RV1(i)}. Visually- and electrically generated V1 responses were compared. RESULTS: During the course of this work we: (i) characterized the response of V1 neurons to visual stimuli according to response magnitude, duration, spiking rate, and the distribution of interspike intervals; (ii) experimentally tested the dependence of V1 responses on stimulation parameters such as intensity, frequency, duration, etc., and determined the ranges of these parameters generating the desired cortical activity; (iii) identified similarities between responses of V1 useful to compare the naturally and artificially generated neuronal activity of V1; and (iv) by modifying the stimulation parameters, we generated artificial V1 responses similar to those elicited by visual stimuli. Generation of predictable and consistent phosphenes by means of artificial stimulation of the LGN is important for the feasibility of visual prostheses. Here we proved that electrical stimuli to the LGN can generate V1 neural responses that resemble those elicited by natural visual stimuli.