Cones Continue to Adapt to the Dark After Rods Have Reached Their Maximum Sensitivity

Dark Adaptation

Dark adaptation functions quantify the ability of the rod and cone systems to recover sensitivity (i.e., regenerate photopigment) after exposure to light.

From: Retina (Fifth Edition) , 2013

Color Vision and Night Vision

Andrew P. Schachat MD , in Ryan's Retina , 2018

Rod and Cone Functions

Differences in the anatomy and physiology (seeChapter 4, Autofluorescence imaging, andChapter 11, Diagnostic ophthalmic ultrasound) of the rod and cone systems underlie different visual functions and modes of visual perception. The rod photoreceptors are responsible for our exquisite sensitivity to light, operating over a 10⁸ (100 millionfold) range of illumination from near-total darkness to daylight. Cones operate over a 10¹¹ range of illumination, from moonlit night light levels to light levels that are so high they bleach virtually all photopigments in the cones. Together the rods and cones function over a 10¹⁴ range of illumination. Depending on the relative activity of rods and cones, a light level can be characterized as photopic (cones alone mediate vision), mesopic (both rods and cones are active), or scotopic (rods alone mediate vision). ¹ In the literature, the terms photopic vision and scotopic vision are used to reflect cone and rod vision, respectively.Table 12.1 shows this overlapping range of rod and cone activities.

The distribution of rods and cones in the retina (seeChapter 4, Autofluorescence imaging) is also reflected in visual function. The greatest sensitivity to light occurs in the midperiphery of the visual field, which has a predominance of rods, while high-acuity and good color vision are mediated by the fovea, which has a predominance of cones. Nonetheless, the entire retina, with the exception of a very small area within the fovea, is capable of mediating night vision, and color vision is present throughout the visual field with daylight stimulation of the entire retina. The following sections will introduce rod and cone differences in light adaptation, spectral sensitivity, and spatial/temporal sensitivity.

Light Adaptation

Photoreceptors, whether they are rods or cones, respond well to only a small range of variations in illumination within a steady adapting background. ² However, adaptation mechanisms adjust photoreceptor sensitivity so that this small range of responses is always centered near the current adaptation level, even though adaptation levels can vary over a wide range. This behavior forms the basis for the large operating range of the visual system.

It is possible to assess light adaptation behavior by measuring a threshold for the perception of an increment in light on a large, steady background field. As the background light level is increased, the increment threshold starts to increase. Rods and cones behave differently in this regard. For the rod system, as shown inFig. 12.1A, the increment threshold increases steadily over almost a thousandfold range. With further increases in background adaptation levels, an increment is not detected, no matter how much additional test light is presented as an increment, due to rod saturation. In comparison, the cone system, as shown inFig. 12.1B, shows a continuous steady increase in the increment threshold with increases in background illumination, even at light levels that bleach almost the entire amount of available photopigment. The portion of the curve that rises linearly with illumination levels is called the Weber region (Fig. 12.1). In the Weber region, an incremental light can be detected when it is a constant proportion (i.e., the Weber fraction) of the background light level. Different photoreceptor systems have a characteristic Weber fraction. Cones have lower Weber fractions than rods. Under optimal conditions, the cone system can detect a light level difference of 1%, while rods need a light change of 20%.

Inherited retinal disorders

Michel Michaelides , ... Anthony T Moore , in Pediatric Ophthalmology and Strabismus (Fourth Edition), 2013

Electrophysiology and psychophysics

Dark adaptation is severely delayed in fundus albipunctatus (FA), reflecting abnormal regeneration of rhodopsin. The rod-cone break is delayed and full rod adaptation may take many hours. Rod ERGs are markedly abnormal, with the rod-specific ERG (DA 0.01) being undetectable under standard conditions, but becoming normal following prolonged dark adaptation ( Fig. 44.4). The dark-adapted bright flash ERG (DA 11.0), which after standard dark adaptation arises in dark-adapted cones, can have a low b : a ratio; a red flash stimulus under dark adaptation shows a normal cone component but an undetectable rod component and prevents confusion with a form of CSNB associated with a negative ERG. To confirm the diagnosis of FA it is necessary to exceed the ISCEV ERG standard recommendations for dark adaptation considerably. Most but not all patients with RDH5 mutations show full recovery of rod function with extended dark adaptation. This contrasts with the findings in retinitis punctata albescens (see below), related to mutation in RLBP1, and usually allows the distinction between the two disorders.

There are two forms of FA, one in which cone ERGs are normal, and a rarer form described as fundus albipunctatus with cone dystrophy and negative ERG. ⁹

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Progressive and "Stationary" Inherited Retinal Degenerations

Myron Yanoff MD , in Ophthalmology , 2019

Dark Adaptation Testing

Night vision symptoms occur early in the course of RP disease and must be evaluated by using dark adaptation studies. One of the instruments to do this is the Goldmann-Weekers dark adaptometer. The patient is placed in darkness and asked to detect the dimmest possible (threshold) light, which becomes progressively dimmer as time proceeds. Final absolute threshold sensitivity is normally reached after 30–40 minutes in the dark. An alternative test strategy is to determine only the final thresholds after 45–60 minutes in the dark. Thresholds are tested in several different retinal locations to sample the distribution of disease. Some patients who complain of difficulty seeing at night are found to have normal dark-adapted thresholds. Such patients may have under corrected myopia, and the complaint is really of blurred vision in dimmer light. Other patients may have maculopathy and notice worse acuity in dimmer light, even though normal rod-mediated, absolute dark sensitivity is maintained.

Vision II

A. Stockman , L.T. Sharpe , in The Senses: A Comprehensive Reference, 2008

2.06.3.1.1 Scotopic luminous efficiency

Scotopic luminous efficiency is comparatively straightforward, since it depends on the activity of a single univariant photoreceptor type, the rods. Thanks to univariance, scotopic luminous efficiency fulfils the basic requirement of any system of photometry that the luminous efficiency of any mixture of lights is the sum of the efficiencies of the components of the mixture; otherwise known as Abney's Law (Abney, W. d. W. and Festing, E. R., 1886; Abney, W. d. W., 1913). Figure 5 shows the scotopic CIE 1951 V′(λ) function (white line), which is based on original data from Crawford B. H. (1949) and Wald G. (1945).

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Structure and Function of Rod and Cone Photoreceptors

Andrew P. Schachat MD , in Ryan's Retina , 2018

Dark Adaptation

The process oflight adaptation described above represents the mechanisms that desensitize phototransduction during steady background light. Despite the push toward desensitization by these mechanisms, several of which depend on the ROS Ca²⁺ concentration, there is a simultaneous pull toward sensitization. Adaptive mechanisms that pull the system toward the "dark" state (collectively coined " dark adaptation ") play a crucial role in sensitivity maintenance. Dark adaptation has been classically studied by exposing dark-adapted subjects, or animal retinas, to bright light that bleaches (i.e., causes acis totrans isomerization of retinal) the visual pigment and depresses sensitivity, and then observing the recovery with time. While cones recover sensitivity within seconds to minutes, rods take tens of minutes to recover to levels comparable to the dark-adapted state. ¹⁵² This slow recovery is attributable to many biochemical processes within rods that quench phototransduction activity fully and reestablish the dark-adapted condition. Among these is the rapid and continuous turnover of the visual pigment, which in rods requires tight apposition with the RPE. Additionally, mechanisms that reset the distribution and state of phototransduction proteins are critical to establish sensitivity. These mechanisms include the decay of long-lasting visual pigment intermediates, such as MetaIII rhodopsin (reviewed inreference 153), and reversing the light-dependent movement of proteins such as Tα, recoverin, and arrestin back to their respective compartments (reviewed inreference 143). The clinical importance of dark adaptation is manifest in pathologic perturbations of this process that lead to a number of blinding eye diseases, including retinal degeneration and diseases of retinoid deficiency.

Electrogenesis of the Electroretinogram

Laura J. Frishman , in Retina (Fifth Edition), 2013

Origin of the scotopic threshold response

For very weak flashes from darkness, near psychophysical threshold in humans, ^33,90 small negative (n) and positive (p) STR dominate the ERG of most mammals that have been studied. This response, which is more sensitive than the b-wave (or a-wave) and saturates at a lower light level than either component, was thus named because of its sensitivity. ⁶³ As shown in Fig. 7.7, for the monkey and human, the nSTR at stimulus onset dominates the dark-adapted diffuse flash ERG in response to the weakest stimuli. The nSTR is distinct from the scotopic a-wave, although it can appear as a "pseudo a-wave" at light levels where it can be removed by suppressing inner retinal activity pharmacologically. ^121,122 The STRs occur in response to stimuli much weaker than those that elicit more distally generated waves of the ERG because convergence of the rod signal in the retinal circuitry increases the gain of responses generated by inner retinal neurons.

The nSTR was initially observed to be generated more proximally (IPL) than PII (INL) in intraretinal depth analysis studies in cats. ⁶³ As shown in Fig. 7.21, the field potential recorded in proximal retina in response to a weak diffuse stimulus was negative-going for the duration of the stimulus, and returned slowly to baseline after light offset. For stimuli too weak to elicit PII, the nSTR reversed polarity in midretina and became a positive-going signal in the mid- and distal retina. This reversal suggests a source proximal to, and a sink distal to, the reversal point (see description of the Müller cell mechanism, below). For stronger stimuli, the reversed nSTR in mid- and distal retina was replaced by PII, which then dominated the ERG. The similarity of the onset times and timecourse of the proximal retinal STR and the negative STR in the cat vitreal ERG can be seen in Fig. 7.21.

The nSTR also can be separated from PII using pharmacologic agents (GABA, glycine, or NMDA ^30,90,121 ) to suppress responses of the amacrine and ganglion cells proximal to bipolar cells. These agents remove the STR, but not PII (Fig. 7.15). In contrast, APB eliminates both the scotopic b-wave (PII) and STR, indicating that the STR will not be generated if the primary rod circuit is no longer mediated by rod bipolar cells (Fig. 7.2).

There is a similarly sensitive positive STR in the scotopic ERG of animals that have a negative STR. ^40,90 Because the pSTR is small and of opposite polarity to the nSTR, it can easily be cancelled out in the ERG. An instance of this can be seen in the dark-adapted macaque ERG in Fig. 7.7. The delayed onset of nSTR for the weakest stimulus is due to the presence of a pSTR that is slightly larger than the nSTR at early times. In response to a stimulus about 1 log unit higher (just above), the pSTR rides on the emerging PII as an early positive potential. Most pharmacologic agents that eliminate the nSTR also eliminate the pSTR. ^40,90 For example, NMDA eliminated both the nSTR and pSTR in the macaque ERG for responses such as those seen for the two weakest stimuli in Fig. 7.7 (Frishman, unpublished observations).

A linear model of the contributions of pSTR, nSTR, and PII to the dark-adapted cat ERG is shown in Fig. 7.22. The model assumes that each ERG component initially rises in proportion to stimulus strength, and then saturates in a characteristic manner, as has been demonstrated in single-cell recordings in mammalian retinas, as well as for ERG a- and b-waves in numerous studies. Only with the inclusion of a small pSTR does the model accurately predict the whole ERG at a given "fixed" time in response to a weak stimulus. The model was fit in Fig. 7.22 to responses measured at 140 ms after a brief full-field flash (<5 ms), which was the peak of the nSTR in the cat scotopic ERG. Similar models have been applied to mouse ⁹⁰ and human ERG. ⁴⁰

K⁺ Müller cell mechanism for generation of the STR

The STR, like the M-wave, is associated with Müller cell responses to [K⁺]_o released by proximal retinal neurons. In intraretinal studies in cat, a proximal increase in [K⁺]_o was observed that had clear similarities to the local STR that was simultaneously recorded: the dynamic range from "threshold" to saturation of the light-evoked proximal [K⁺]_o increase was similar to that of the field potentials, and the retinal depth maxima for the two responses were the same. ^22,54 A causative role for the [K⁺]_o increase in generating the nSTR (and a slow negative response in the vitreal ERG following the initial STR) was supported by the finding (Fig. 7.23) that Ba²⁺ removed the proximal retinal field potential and the nSTR in the ERG but did not, initially, eliminate the light-evoked increase in [K⁺]_o. The cornea-negative polarity of the nSTR suggests a distally directed Müller cell K⁺ current (similar to M-wave and PIII currents in the vascularized cat retina). As noted above for the light-adapted M-wave, in the dark-adapted retina Ba²⁺ also appears to block K⁺ siphoning by the Müller cells. Whereas the proximal [K⁺]_o increase remained intact when related field potentials were abolished, the distal [K⁺]_o increase was eliminated by Ba²⁺.

Neuronal origins of the STR

Whether the neurons involved in the genesis of the nSTR and pSTR are amacrine or ganglion cells is species-dependent. In monkeys it is likely that the nSTR arises predominantly from ganglion cells. It was absent in eyes in which the ganglion cells were eliminated as a consequence of experimental glaucoma ¹¹² and by intravitreal injection of TTX to block Na⁺-dependent spiking activity of those neurons; the pSTR remained intact. In contrast, in cats and humans ¹²² as well as in rodents, ³ the nSTR is not eliminated by ganglion cell loss, and thus may be more amacrine cell-based. In rodents the pSTR relies upon the integrity of ganglion cells. A characteristic of Müller/glial cell-mediated ERG components is their slow timecourse. Glial cell mediation of the nSTR was demonstrated most directly in cat, but the timecourse of the nSTR is slow in all species. Glial mediation may explain the similarity in timecourse of nSTR across species regardless of the particular type of neuron producing the local changes in proximal [K⁺]_o that generate the response.

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Basic Science, Inherited Retinal Disease, and Tumors

Laura J. Frishman , in Retina (Fourth Edition), 2006

A K⁺-Müller cell mechanism for generation of the scotopic threshold response

The STR, like the M-wave, is associated with Müller cell responses to [K⁺]_o released by proximal retinal neurons. ^{60, 61} Frishman & Steinberg ⁶¹ identified a proximal increase in [K⁺]_o with obvious functional similarities to the STR that was simultaneously recorded in proximal retina: the dynamic range from "threshold" to saturation of the light-evoked proximal [K⁺]_o increase was similar to that of the field potentials, and the retinal depth maxima for the two responses were the same.

A causative role for the [K⁺]_o increase in generating the nSTR (and a slow negative response in the vitreal ERG following the initial STR) was supported by the finding that Ba²⁺ eliminated the proximal retinal field in the cat and the nSTR in the ERG but did not, initially, eliminate the light-evoked increase in [K⁺]_o. The cornea-negative polarity of the nSTR suggests a distally directed Müller cell K⁺ current (similar to M-wave and PIII currents in the vascularized cat retina). As illustrated in Figure 6-31 for the light-adapted M-wave, Figure 6-36 shows that in the dark-adapted retina Ba²⁺ also appeared to block K⁺ siphoning by the Müller cells. Whereas the proximal [K⁺]_o increase remained intact when related field potentials were abolished, the distal [K⁺]_o increase was eliminated by Ba²⁺.

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Primary Photoreceptor Degenerations: Retinitis Pigmentosa

M.E. Pennesi , ... R.G. Weleber , in Encyclopedia of the Eye, 2010

Diagnostic Tests for RP

Dark Adaptation

Dark adaptation can be a useful test in patients with RP. Patients who manifest with a rod–cone dystrophy will usually have a detectable increase in final dark-adapted thresholds and show delayed dark-adaptation curves. Prolonged dark adaptation is especially common among patients with RHO mutations. Elevations of the early cone segment of the dark-adaptation curve may be particularly noticed by patients, more so than elevations of the rod segment ( Figure 4 ).

Figure 4. Example of dark-adaptation curves in a normal subject (dashed lines represent the mean normal response, dotted lines represent the upper limit of normal) and patients with retinitis pigmentosa (solid lines). From Weleber, R. and Evan, K. G. (2006). Retinitis pigmentosa and allied disorders. In: Ryan, S. J. (ed.) The Retina, 4th edn., vol. 1, chap. 17, pp. 395–498. Philadelphia, PA: Elsevier.

Visual Fields

Visual fields are not only useful for making the diagnosis of RP, but are also one of the most useful objective methods for monitoring progression of the disease. Decreased visual-field sensitivity results from photoreceptor loss ( Figure 5 ).

Figure 5. Example of a mildly abnormal kinetic visual field in a patient with early retinitis pigmentosa demonstrating the responses to different-sized targets. The gap between the size III4e and size I4e isopters is greater than normal, indicating loss of sensitivity in this region. The blind spot (region containing the optic nerve head and therefore no photoreceptor cells) is plotted in each eye just temporal to the fovea.

The earliest change seen as measured by kinetic perimetry is concentric constriction or decreased sensitivity with static perimetry in diffuse disease and relative midperipheral scotomas seen in the in regional disease. As these midperipheral scotomas or regions of decreased sensitivity enlarge and deepen, severe tunnel vision results. Eventually, macular function fails and visual field becomes difficult or impossible to measure by conventional perimetry. Although visual function may be reduced to light perception only, it is rare for patients to become completely blind. With the exception of female carriers in X-linked RP, visual-field loss is usually symmetrical. Marked asymmetry should raise concern for diseases that mimic RP ( Figure 6 ).

Figure 6. Kinetic visual fields obtained from patient with retinitis pigmentosa. Note the relative preservation of inferior fields, which correlated with preserved superior retina. From Weleber, R. and Evan, K. G. (2006). Retinitis pigmentosa and allied disorders. In: Ryan, S. J. (ed.) The Retina, 4th edn., vol. 1, chap. 17, pp. 395–498. Philadelphia, PA: Elsevier.

The rate of visual-field loss has been shown to be exponential. This rate is thought to be similar for the different forms of inheritance once correction has been made for the critical age of onset. Massof and Finkelstein found that patients lost about 50% of their visual field every 4.5   years. The superior visual field, which corresponds to the inferior retina, is often more affected than inferior visual fields. Based on this finding, it has been suggested that increased levels of light may play a role in accelerating retinal degeneration and this in turn may play a role in the forms of RP with greater damage in the inferior retina.

Electroretinograms

ERGs play a crucial role in the diagnosis of RP because these electrophysiological recordings are sensitive enough to detect decreased photoreceptor function early in the disease when fundus findings and visual fields may be minimally altered. In addition, ERGs are particularly useful to assess visual function in preverbal infants and children. Almost all patients with symptomatic RP will have detectable changes on the ERG at the time of diagnosis. While the ERG is useful for the diagnosis of RP, visual fields are better for monitoring of the course of the disease. In severe cases of RP, such as LCA, the ERG may be not recordable.

Patients with RP can show decreased amplitude and timing of the major components of the ERG. Caution must be taken when interpreting decreases in the amplitude of an ERG because poor contact of the electrodes, deviations of the eye, and high myopia can affect the amplitude of the signal. When present, delayed timing tends to be a more robust indicator of dysfunction.

By analyzing the different components of the ERG, different forms of RP can be classified. Degeneration of the rod and cone photoreceptors leads to a decrease in the amplitude of different waveforms of the ERG and can also increase the timing or latency of the peaks of these waveforms. The most common forms of RP manifest as a rod–cone dystrophy and the first detectable changes will be apparent on the scotopic ERG. Decreases in the b-wave amplitude and timing of the peak of the b-wave are indicative of early rod photoreceptor death. Further loss of rod cells leads to further decreases in the b-wave amplitude and decreased amplitude of the a-wave responses at higher intensities. Patients with a cone–rod dystrophy have normal, or lesser defect of b-wave responses to dim scotopic stimuli, but typically have more markedly abnormal ERGs to 30-Hz flicker or single-flash stimuli measured under photopic conditions ( Figures 7–9 ).

Figure 7. ERGs recorded from a patient with autosomal recessive RP (left column) compared to a control patient (right column). This patient is demonstrative of a rod–cone dystrophy. There is a flat response to the dim blue flash under scotopic conditions, which specifically stimulates rods. The bright flash under scotopic conditions normally elicits mixed responses from both rods and cones. In this case, the response is severely attenuated and the small amount of signal is likely coming from the cone system. Under light-adapted conditions (photopic single flash and 30-Hz flicker), which selectively stimulate the cones, the response is only slightly decreased consistent with the categorization of a rod–cone dystrophy.

Figure 8. ERGs recorded from a patient with peripherin/RDS null mutation (left column) compared to a control patient (right column). This patient is demonstrative of a rod–cone dystrophy where the rods and cones are equally affected. It is of importance that peripherin is expressed in both rods and cones. There is a severely diminished response to the dim white flash under scotopic conditions, which specifically stimulates rods. The bright flash under scotopic conditions normally elicits a mixed response from both rods and cones. In this case, the response is severely attenuated. Under light-adapted conditions (photopic single flash and 30-Hz flicker), which selectively stimulate the cones, the response is also severely decreased consistent with the categorization of an equal rod–cone dystrophy.

Figure 9. ERGs recorded from a patient with autosomal recessive RP (left column) compared to a control patient (right column). This patient is demonstrative of a cone–rod form of RP. There is a mildly diminished response to the dim blue flash under scotopic conditions, which specifically stimulates rods. The bright flash under scotopic conditions normally elicits a mixed response from both rods and cones. In this case, the response is only moderately attenuated. Under light-adapted conditions (photopic single flash and 30-Hz flicker), which selectively stimulate the cones, the response is severely decreased consistent with the categorization of a cone–rod dystrophy.

Fundus Photography/Fluorescein Angiography

Documentation by fundus photography can assist in monitoring changes in patients with RP. Fluorescein angiography in patients with RP will demonstrate hyperfluorescence in areas of RPE atrophy and can highlight areas of cystoid macular edema. However, fluorescein angiography has largely been supplanted by optical coherence tomography (OCT) for detecting cystoid maculopathy. In addition, concerns about light exposure accelerating certain forms of RP in animal models have prompted many ophthalmologists to exercise caution in obtaining excessive photographs.

Optical Coherence Tomography

OCT provides a noninvasive cross-sectional image of the retina. It is very useful in patients with RP when there is a question of cystoid macular edema. The ability to detect cystoid macular edema by OCT often obviates the need to get a fluorescein angiogram.

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Functional vision changes in the normal and aging eye

Bruce P. Rosenthal , Michael Fischer , in A Comprehensive Guide to Geriatric Rehabilitation (Third Edition), 2014

Dark adaptation

Dark adaptation, or the ability, to adjust to new levels of illumination, such as going from the outdoors to the indoors, may be very apparent and debilitating from retinal diseases (e.g. macular degeneration, macular edema, diabetic and hypertensive retinopathy). Adapting to changes in lighting levels is exemplified by the effect of a camera flash into the eye or entering a dark movie theatre. The response time in adapting, especially for elderly, may result in a fall from an object not obvious in the environment. Absorptive lenses and filters may be beneficial in minimizing the adaptation time as well as enhancing the contrast. Stereoacuity vision loss may often result in the vision being much poorer in one eye. This disparity between the two eyes may manifest itself in such tasks as threading a needle or tying shoelaces.

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Environmental design

Mary Ann Wharton PT, MS , in Geriatric Physical Therapy (Third Edition), 2012

Dark adaptation.

Dark adaptation, or the ability of the eye to become more visually sensitive after remaining in darkness for a period of time, is delayed in older persons. One reason for this visual change is the smaller, miotic pupil, which limits the amount of light reaching the periphery of the retina. It is this area of the retina that contains the rods, which are sensitive to low light intensities. Another reason for delayed dark adaptation in older individuals is the metabolic changes in the retina. The oxygen supply to the rod-dense area of the retina diminishes as a result of vascular changes, which, in turn, affect the efficiency of the rods to respond to low levels of illumination. As a result of these changes, older persons have difficulty adapting to darkness and to abrupt and extreme changes in light. ^2-5

Use of a night-light is recommended to assist in overcoming the decreased ability for the eyes to adapt to the dark. Red light stimulates the cones but not the rods, allowing an older person to see well enough by red light to function in the dark. Therefore, a red bulb is suggested because it reduces the time required for adaptation to the dark and while permitting the older individual to see well enough to function. It is also recommended that older individuals carry a pocket flashlight to aid in transition to dimly lit environments. Improving lighting at the point of entry to an area, through pull cords or light switches near the entrance to a room, is also recommended. Automatic timers or keeping a light on at all times in dimly lit areas can prevent older individuals from having to enter a darkened room. ^{3 , 5 , 15}

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