Ординатура / Офтальмология / Английские материалы / Ocular Periphery and Disorders_Dartt, Bex, Amore_2011

Glossary

Accommodation – A change in the refractive power of the crystalline lens of the eye.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) – The ganglion cells expressing a photopigment, melanopsin, that is intrinsically light sensitive.

Miosis – Pupillary constriction. Mydriasis – Pupillary dilation.

Pupillary light reflex (PLR) – The constriction of the pupil that is elicited by an increase in illumination of the retina.

Advantages of a Mobile Pupil

The normal human pupil can change diameter from 8 to 1.5 mm, which corresponds to approximately a 30-fold change in area and almost a 1.5-log unit change in retinal irradiance. Although the visual system can operate over a 10-log unit range of lighting levels through the process of adaptation, it can take several minutes for optimum sensitivity to return after an abrupt increase or decrease in retinal illumination. The rapid control of retinal irradiance by the iris allows the visual system to more quickly regain optimal sensitivity by dampening fast changes in ambient lighting levels and by requiring less retinal adaptation for a given change in environmental lighting levels.

However, changes in pupil size affect not only retinal illumination, but also diffraction, optical aberrations, and depth of focus of the eye. These factors differentially affect visual performance and, given changing environmental lighting conditions and visual tasks, the nervous system continuously modulates pupil diameter for optimal visual performance.

The diffraction of light rays by an aperture is a major limiting factor in the resolution of an image in any optical system. The amount of disruption in image quality caused by diffraction at a circular aperture decreases as the size of the opening increases. Therefore, as pupil diameter increases, there is decreased degradation in retinal image quality caused by diffraction. In contrast to diffraction, the image-degrading effects of optical aberrations increase as aperture diameter increases. Therefore, as pupil diameter increases, the degradative effects of optical aberrations

also increase, and offset the benefits gained by reduced diffraction at larger pupil diameters. Over the normal range of pupillary diameter, diffraction impacts image quality less than optical aberration, and the optimal pupil diameter is therefore approximately between 2 and 4 mm.

Along with diffraction and optical aberrations, defocus is an important determinate of retinal image quality. Although the pupil does not refract or focus light, it influences the depth of field of the eye. Depth of field is the range of distance in depth in which objects appear to be in focus. For example, when one reads a book, the power of the crystalline lens of the eyes changes in order to bring the text on the page into focus through a process called accommodation. With the eyes accommodated on the book, all objects within a range in front of and behind the book will also appear in focus. This range is called the depth of field and it is primarily dependent both on viewing distance and pupil diameter. When the viewing distance is held constant, the depth of field increases with decreases in pupil diameter, and therefore the pupil diameter can affect the focus of the retinal image.

Clearly, a mobile pupil allows the nervous system to optimize retinal irradiance, diffraction, ocular aberrations, and depth of focus despite differing conditions and visual tasks. For example, across a range of daylight (photopic) luminances, pupil size corresponds to that required for the highest visual acuity, and the maximal information capacity of the retinal image. On the other hand, under low light (scotopic) conditions in which poorer retinal image quality can be tolerated due to the lower resolution of rod photoreceptors, the pupil dilates sufficiently to maximize the retinal illumination. Further evidence for the optimization of pupil diameter for differing visual tasks is evident in the pupillary near response (PNR). When the viewing distance changes from far to near, the pupils constrict to increase the field of view and reduce the retinal image defocus. This compensates for the decrease in the effective field of view that naturally occurs when viewing distance decreases (see the section titled ‘Pupillary near response’ for more details).

Overview of the Pathways Controlling

Pupil Diameter

A summary diagram of the afferent, central, and efferent pathways controlling pupil diameter is shown in Figure 1. This figure shows the iris musculature innervated by autonomic efferents from both the parasympathetic and sympathetic components of the autonomic nervous system

(ANS). The parasympathetic component of the ANS innervates the sphincter pupillae muscle of the iris. The preganglionic parasympathetic fibers controlling the sphincter pupillae originate from neurons in the Edinger–Westphal (EW) nucleus, the autonomic subdivision of the third cranial nerve nucleus, and travel through the third cranial nerve to the ciliary ganglion, which is located within the orbit of the eye (see Figure 1). Within the ciliary ganglion, the preganglionic pupilloconstriction neurons form cholinergic, nicotinic synapses with the postganglionic neurons.

The axons of these postganglionic neurons leave the ciliary ganglion to enter the eye through the short ciliary nerves and travel to the iris. Here, they release acetylcholine, which acts on the muscarinic receptors of the sphincter pupillae (see Figure 2).

The sympathetic component of the ANS innervates the dilator pupillae muscle. The preganglionic sympathetic neurons, which control pupillary dilation, are located in the C8-T1 segments of the spinal cord, a region termed the ciliospinal center of Budge (and Waller). The

axons of these preganglionic neurons project to the sympathetic chain and travel in the sympathetic trunk to the superior cervical ganglion. Within the superior cervical ganglion, the preganglionic axons form nicotinic, cholinergic synapses with postganglionic pupillodilation neurons. The axons of these postganglionic neurons project from the superior cervical ganglion to the orbit, where they enter the eye through the short and long ciliary nerves and travel to the iris (see Figure 1). Here, they release norepinephrine, which acts on the adrenoreceptors of the dilator muscle (see Figure 2).

Iris Musculature

In a cross-section of the iris, the sphincter pupillae can be seen as an annular band of smooth muscle (100–170 mm thick; 0.7–1.0 mm wide) encircling the pupil (Figure 2). The sphincter, which is located in the posterior iris immediately anterior to the pigmented epithelium, interdigitates with the surrounding stroma and connects to the dilator muscle fibers. The smooth muscle cells of the sphincter are clustered in small bundles and connected by gap junctions. These gap junctions ensure synchronized contraction of the sphincter muscle. The sphincter receives muscarinic, cholinergic innervation from the short ciliary nerves – parasympathetic, postganglionic fibers arising from the ciliary ganglion.

The dilator pupillae is composed of radially oriented smooth muscle fibers that are myoepithelial in origin. Individual fibers are approximately 50 mm long and 5–7 mm wide. In the pupillary zone, dilator muscle processes fuse with the sphincter pupillae, while peripherally, their processes attach to the ciliary body. Contraction of the dilator muscle pulls the pupillary margin toward the ciliary body.

Pupillary Light Reflex

Description

The pupillary light reflex (PLR) is the constriction of the pupil that is elicited by an increase in illumination of the retina. The direct PLR, present in virtually all vertebrates, is the constriction of the pupil in the same eye as that stimulated with light. The consensual PLR is the constriction of the pupil in the eye opposite to the eye stimulated with light. In mammals with laterally placed eyes, such as the rat and rabbit, the direct PLR is more pronounced than the consensual PLR. However, in those mammalian species with frontally placed eyes, such as humans and monkeys, the direct and consensual PLRs are essentially equal. An example of a human consensual PLR produced by two different wavelengths of light is shown in Figure 3. The PLR has traditionally been divided into two separate pathways based on the clinical manifestations of the defects in this reflex. The afferent pathway is composed of both the retinal cells that project to the pretectum as well as their recipient neurons, which project bilaterally to the EW nucleus (Figure 1). The efferent pathway is composed of the preganglionic pupilloconstriction fibers of the EW nucleus and their postganglionic recipient neurons in the ciliary ganglion, which project to the sphincter muscle of the iris (Figure 1).

Afferent Pathway

The first neurons in the afferent pathway of the PLR are retinal ganglion cells. It has recently been recognized that this reflex in rodents and primates is driven predominantly by a unique subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) which project to the pretectal olivary nucleus (PON), a small nucleus in the

Time (s)

Figure 3 Pupilloconstriction elicited by a 10-s light stimulus of 493-nm wavelength light at 14.0 log quanta cm–2 per second irradiance (blue trace), and 613-nm wavelength light at 14.1 log quanta cm–2 per second irradiance (red trace). Note that a 473-nm stimulus, which effectively activates the intrinsic photoresponse of intrinsically photosensitive retinal ganglion cells (ipRGCs), drives a larger pupillary response than the 613-nm stimulus (red trace), which does not effectively activate the intrinsic photoresponse of ipRGCs at this irradiance level. Note that the pupilloconstriction induced by the 473-nm light is maintained following stimulus offset. From McDougal, D. H. and Gamlin, P. D. R. (2008). Pupillary control pathways. In: Basbaum, A. I., Kaneko, A, Shepherd, G. M., et al. (eds.) The Senses:

A Comprehensive Reference, Vol 1: Vision 1, pp. 521–536. San Diego, CA: Academic Press.

pretectum; the pretectum is located in the dorsal lateral aspect of the midbrain at the level of the superior colliculus (see Figure 1).

Intrinsically photosensitive retinal ganglion cells

Prior to 2000, it was assumed that the PLR was driven by retinal ganglion cells which received light signals exclusively from rod and cone photoreceptors, which up to that time were the only known photoreceptive cells in the retina. However, recent studies have demonstrated that the PLR is driven predominantly by retinal ganglion cells which, unlike any other retinal ganglion cell class, are intrinsically photosensitive. The intrinsic photoresponse of these neurons, which is mediated by the photopigment melanopsin, presumably compensates for the adaptation of rod and cone photoreceptors, and serves to maintain pupilloconstriction during steady-state exposure at all photopic (daylight) illuminance levels. In addition to their intrinsic light-driven signal, it is clear that ipRGCs receive rod and cone inputs. In response to a pulse of light, intracellular recordings from these cells show a characteristic transient burst of neural activity at stimulus onset, which rapidly decays to a plateau of sustained activity that

often extends well past stimulus offset. The initial burst of neural activity is mediated by a rapidly adapting conemediated photoresponse, while the sustained activity is driven predominantly by the intrinsic response of these cells, although there is growing evidence for a rod contribution to this sustained activity under steady-state lighting conditions.

IpRGCs project to the PON of rodents and primates, and they play a major role in pupillary responses. Monkeys and rodents with nonfunctional rod and cone photoreceptors but functional melanopsin-containing ipRGCs display a PLR; however, the reflex has a higher irradiance threshold than normal. Mice with ipRGCs lacking melanopsin also display PLR, but their pupils fail to constrict maximally in bright lights. Taken together, these results show that both the intrinsic photoresponse of ipRGCs and their classical photoreceptor inputs provide signals of retinal irradiance that drive the PLR. Additional studies further suggest that the influence of rod and cone photoreceptors on the pupillary light reflex is mediated exclusively through their inputs to ipRGCs.

The intrinsic photoresponse of ipRGCs can also affect pupillary behavior in the absence of ongoing light stimulation. As noted above, ipRGCs encode stimulus irradiance through an elevation of firing rate that continues well beyond stimulus offset. Indeed, bright light stimuli can produce a prolonged pupillary constriction in humans that can persist up to 20 min after the light has been extinguished (see Figure 3). Experiments in primates, including humans, demonstrate that this prolonged pupillary constriction in darkness is mediated almost entirely by the intrinsic photoresponse of ipRGCs.

Pretectal olivary nucleus

The first relay in the afferent pathway of the PLR consists of luminance neurons within the PON, which receives direct retinal input. PON luminance neurons are characterized by tonic firing rates that increase with increases in retinal illuminance. In primates, these neurons exhibit a transient burst of activity followed by sustained tonic activity in response to increases in retinal illuminance. In addition, the tonic firing rate of these cells is proportional to retinal illuminance over at least a 3 log unit range of stimulus intensities in primates and in rats. Electrical microstimulation of the PON in rats and monkeys elicits pupilloconstriction at short latencies, and lesions of the PON in rats produce deficits in pupillomotor function. These results strongly suggest that luminance neurons within the PON mediate the PLR. In addition to retinal afferents, the PON also receives significant cortical, ventral thalamic, and midbrain inputs which may also have an influence on the PLR or other pupillary movements. Owing to its importance for the PLR, the best-described efferent projection of the PON is to the EW nucleus. However, the PON has been shown to project to a number

of other targets, such as the hypothalamus, pons, and medulla that may also influence pupillary behavior.

Efferent Pathway

The efferent leg of the PLR begins with preganglionic pupilloconstriction neurons of the EW nucleus that project through the third cranial nerve to the ciliary ganglion (see Figure 1).

The EW nucleus is a distinct nucleus of the midbrain, lying immediately dorsal to the oculomotor complex. It is located just ventral and lateral to the cerebral aqueduct at the level of the superior colliculus (see Figure 1). Evidence for the course of the efferent parasympathetic pupillary pathway and the importance of the EW nucleus in pupilloconstriction comes from electrical stimulation studies in the vicinity of EW nucleus that elicit pupilloconstriction in a variety of animal models. Within the ciliary ganglion, which is approximately 3 mm in size, and located 2–3 mm posterior to the globe and lateral to the optic nerve, the axons of the preganglionic neurons synapse with the postganglionic pupilloconstriction neurons. The axons of these postganglionic neurons leave the ciliary ganglion to enter the eye via the short ciliary nerves to innervate the sphincter muscle of the iris.

Sympathetic Influences on the PLR

It is generally agreed that the parasympathetic pathway discussed above is the primary route of pupillary constriction associated with the PLR. However, there is some evidence that increases in retinal illumination may cause a reduction in the tone of the dilator muscle of the iris through the sympathetic pathway outlined in Figure 1, and thus enhance the PLR. Studies in cats have shown a light-induced inhibition of postganglionic pupillodilation fibers at the level of the long ciliary nerves, and preganglionic, pupillodilation fibers at the level of the cervical sympathetic nerve. These studies found that the pupillodilation fibers were inhibited by light in an intensitydependent manner, that is, a more intense light brought about a greater inhibition in firing rate. However, these findings have not been replicated in primates, in which the evidence suggests that the sympathetic system does not contribute to the dynamics of the PLR and only contributes to tonic modulation of pupil diameter.

The Pupillary Near Response

Description

The PNR is the pupillary constriction associated with a change in viewing distance from far to near that occurs in primates including humans. When the eyes move from viewing a far object to viewing a near object, three

oculomotor responses occur. The eyes converge to bring the image of the object onto the fovea of each retina, the refractive power of the crystalline lens is adjusted to bring the image of the object into focus on the retina, and the pupil constricts. These collective processes are classically referred to as the near response or the near triad.

Efferent Pathway of the PNR

The PNR is thought to be driven solely by an increased drive to the sphincter muscle of the iris through the parasympathetic efferent pathway. Therefore, the neural control pathway of the PNR shares a common efferent pathway with the PLR, although the afferent inputs responsible for the PNR are more complex. The neural signals driving these two reflexes most likely converge at the EW nucleus, since the activity of PON luminance neurons is not correlated with pupil constriction during near viewing. Further, certain clinical neurological conditions are characterized by an intact PNR despite the absence of the PLR (light-near dissociation).

It is generally accepted that preganglionic neurons in the EW nucleus drive the PNR as well as the PLR. However, it has not been determined if separate subpopulations of neurons exist in EW nucleus devoted exclusively to either the PLR or the PNR, or whether the same population of neurons drives pupillary constriction in both reflexes, although the latter seems most likely.

Afferent Influences on the PNR

Early investigations attempted to determine whether the PNR was driven primarily by ocular convergence or accommodation, the other two components of the near triad. Some studies found that the PNR was more closely associated with accommodation than with convergence. Other studies found a greater association with convergence, and even reported that the PNR was totally absent during some blur-driven accommodative responses. These conflicting results are likely a product of an incomplete disassociation between the convergence and accommodation systems during these experiments, as these two systems have been shown to be highly interdependent. A more modern view of the afferent influences controlling the PNR has recently emerged. In this view, the PNR is not seen as resulting from either accommodation or convergence alone, but as a separate output of the neural pathways that drive both accommodation and convergence.

A number of brain areas play a role in controlling the near triad. These include cortical areas, such as extrastriate cortex, parietal cortex, frontal eye fields, as well as the cerebellum and the midbrain. Of particular interest to the PNR, is the supraoculomotor area of the midbrain, which lies just dorsal and lateral to the oculomotor nucleus. The supraoculomotor area contains near response cells which

are modulated by both vergence and accommodation. These cells project to medial rectus motoneurons, and thus contribute to vergence eye movements. It seems likely that these cells also project to EW nucleus and are responsible for carrying the signal from the accommodation and convergence controller to the preganglionic, pupilloconstrictor neurons.

Additional Cortical Influences on Pupillary Responses

In addition to cortical afferents mediating the PNR, the pupil is also influenced by both visual and nonvisual cortical regions. These afferents manifest themselves as small changes in pupil diameter during presentation of visual stimuli such as colored stimuli and gratings, as well as nonvisual stimuli such as auditory tones, and even during higher-order cortical functions such as problem solving. These observations provide clear evidence that cortex exerts an influence on pupillary behavior, which therefore cannot be thought of as entirely reflexive in nature.

Visually Mediated Cortical Influences on Pupillary Behavior

Small pupillary constrictions have been shown to occur in both human and monkeys with the presentation of complex visual stimuli, even when the stimuli do not involve a change in viewing distance or retinal illuminance. Changes in stimulus attributes such as color, spatial frequency, or apparent motion produce such cortically mediated pupillary responses. Deficits in these pupillary responses are observed in humans with lesions to cortical areas involved in processing one or more of these stimulus characteristics. In addition, lesions of rostral inferior temporal cortex but not V4 in macaques abolish pupillary responses to chromatically modulated gratings.

Task-Evoked Pupillary Responses

In the early 1960s, Hess and colleagues published a series of papers which reported modulations in human pupillary diameter associated with complex cognitive processes such as subjective attitudes or mental activity. Later studies failed to replicate the findings relating pupillary dynamics to subjective attitudes, although the findings related to mental activity have been replicated and extensively studied. The small pupillary dilations associated with increased mental activity, or task-evoked pupillary responses (TEPRs), have now become a well-established tool of cognitive psychology. These pupillary responses are generally reported to vary in magnitude from 0.2 to 0.7 mm, and have been shown to correlate with cognitive

load across diverse functions, such as sensory perception, memory, language, and attention. TEPRs have been repeatedly shown to monotonically vary with the degree of mental activity required by a task as measured by other objective criterion such as reaction time and the extent of cortical activation indicated by positron emission tomography (PET) scan, and this has allowed TEPRs to be utilized successfully to empirically test theories of language processing and intelligence.

Although the behavioral phenomenon of TEPRs has been extensively studied and quantified, little is known of the underlying neurophysiology that drives these responses. It has been suggested that they may be driven by noradrenergic projections from the locus ceruleus since the activity of neurons in this nucleus has been show to correlate with both pupil diameter and task-related events.

Influence of Alertness on Pupillary Behavior

Since the muscles of the iris are controlled by the ANS, environmental or physiological conditions which cause changes in overall autonomic function can have a significant effect on pupillary behavior. Even though the environment or physiological conditions which produce the change in autonomic tone may not have a direct influence on the visual system, they may still manifest themselves through an affect on pupil diameter.

Arousal

Situations or stimuli which produce an emotional or startle response often produce a profound pupillary dilation. This effect is mediated through the hypothalamus, the brain area responsible for the integration of autonomic function. This integration allows for the coordination of the various functions of the ANS and often leads to global changes in the balance between the sympathetic and parasympathetic branches of the ANS. For example, an unexpected loud noise may produce a startle response which is characterized by increases in heart rate, respiratory rate, and pupil diameter; it is caused by a systemic increase in sympathetic tone mediated through the hypothalamus. This global increase in sympathetic tone can affect pupil diameter via activation of the pupillodilation centers of the spinal cord and inhibition of the pupilloconstriction neurons of EW nucleus. Neurons within the hypothalamus project to the sympathetic preganglionic pupillodilation neurons of the thoracic spinal cord. This direct effect of hypothalamic activation on pupil diameter can be shown through microstimulation of the posterior hypothalamus, which often causes rapid pupil dilation. Increase in sympathetic tone can also produce inhibition

of pupilloconstriction neurons of EW nucleus via the influence of ascending neuromodulatory pathways.

The hypothalamus is also the site at which autonomic function is regulated by the central nervous system through connections with the limbic system and cortical structures. The limbic system of the brain, which is responsible for emotions and short-term memory, has a direct connection to the hypothalamus and therefore can have significant effects on autonomic balance. Situations or stimuli which produce an intense emotional response are often accompanied by pupillary dilation, which is certainly mediated through limbic connections to the hypothalamus. In addition, cortical influences on the hypothalamus allow a wide variety of stimuli to effect autonomic tone and thus pupil diameter.

Sleep

Sleep has a pronounced effect on the ANS, specifically a reduction in sympathetic outflow and an increase in parasympathetic outflow. Given this overall trend, it is not surprising that pupillary behavior during sleep is characterized by prolonged constriction of the pupil. It has been shown that sleep-induced pupillary constriction persists in animals with lesions of the preganglionic sympathetic pupillodilation fibers. This suggests that the sleepinduced pupillary changes are mediated by an activation of the preganglionic parasympathetic pupilloconstriction fibers of the EW nucleus.

Ascending Neuromodulatory Systems

The ascending neuromodulatory systems of the midbrain and brainstem can have a variety of effects on pupillary behavior. These nuclei are the origin of neuromodulatory fibers which release dopamine, norepinephrine, histamine, and serotonin at a number of brain areas implicated in pupillary control. These neuromodulatory systems appear to be critical in the regulation of sleep and arousal, as well as autonomic regulation and cortical plasticity. In addition to these global neuromodulatory effects, all or some of which could have a profound influence on pupillary behavior, there is some evidence for a direct inhibition of pupilloconstriction neurons in the EW nucleus by adrenergic neurons originating from the locus ceruleus in a number of animal models. However, other studies in humans and rabbits have failed to find this direct noradrenergic inhibition of EW nucleus pupilloconstriction neurons and it has been suggested that this effect might be mediated by dopaminergic neurons in these species. Drugs which agonize or antagonize these neuromodulatory neurotransmitters have been found to differentially

affect pupillary behavior in a wide range of animal models and human studies. These differential effects are most likely due to the both interspecies variability in the projections of these neuromodulatory fibers, as well as the differential activation of multiple brain areas implicated in pupillary behavior due to the extensive projections of these neuromodulators.

Acknowledgments

This work was supported by NIH grant EY09380 and the EyeSight Foundation of Alabama.

See also: Acuity.

Further Reading

Barbur, J. L. (2003). Learning from the pupil – studies of basic mechanisms and clinical applications. In: Chalupa, L. M. and Werner, J. S. (eds.) The Visual Neurosciences, pp. 641–656. Cambridge, MA: MIT Press.

Beatty, J. and Lucero-Wagoner, B. (2000). The pupillary system. In: Cacioppo, J. T., Berntson, G., and Tassinary, L. G. (eds.) Handbook of Psychophysiology, 2nd edn., pp. 142–162. Cambridge: Cambridge University Press.

Berson, D. M. (2003). Strange vision: Ganglion cells as circadian photoreceptors. Trends in Neuroscience 26: 314–320.

Bron, A. J., Tripathi, R. C., Tripathi, B. J., and Wolff, E. (1997). Wolff’s Anatomy of the Eye and Orbit. London: Chapman and Hall Medical.

Busettini, C., Davison, R. C., and Gamlin, P. D. R. (2009). Vergence eye movements. In: Squire, L. (ed.) Encyclopedia of Neuroscience, vol. 10, pp. 75–84. Oxford: Elsevier.

Charman, W. N. (1995). Optics of the eye. In: Bass, M. (ed.) Handbook of Optics, pp. 24.3–24.54. New York: McGraw-Hill.

Gamlin, P. D. (2000). Functions of the Edinger–Westphal nucleus.

In: Burnstock, G. and Sillito, A. M. (eds.) Nervous Control of the Eye, pp. 117–154. Binghamton, NY: Harwood Academic.

Gamlin, P. D. (2005). The pretectum: Connections and oculomotorrelated roles. Progress in Brain Research 151: 379–405.

Gamlin, P. D., McDougal, D. H., Pokomy, J., et al. (2007). Human and macaque pupil responses driven by melanopsin-containing retinal ganglion cells. Vision Research 47(7): 946–954.

Kardon, R. H. (2005). Anatomy and physiology of the autonomic nervous system. In: Miller, N. R., Walsh, F. B., Biousse, V., and Hoyt, W. F. (eds.) Walsh and Hoyt’s Clinical Neuro-Ophthalmology, vol. 3, pp. 649–714. Baltimore, MD: Lippincott Williams and Wilkins.

Kawasaki, A. (2005). Disorders of pupillary function, accommodation, and lacrimation. In: Miller, N. R., Walsh, F. B., Biousse, V., and Hoyt, W. F. (eds.) Walsh and Hoyt’s Clinical Neuro-Ophthalmology, vol. 3, pp. 739–804. Baltimore, MD: Lippincott Williams and Wilkins.

Loewenfeld, I. E. and Lowenstein, O. (1993). The Pupil: Anatomy, Physiology, and Clinical Applications. Ames, IA: Iowa State University Press.

McDougal, D. H. and Gamlin, P. D. R. (2008). Pupillary control pathways. In: Basbaum, A. I., Kaneko, A., Shepherd, G. M., et al. (eds.) The Senses: A Comprehensive Reference, Vol 1: Vision 1, pp. 521–536. San Diego, CA: Academic Press.

Oyster, C. W. (1999). The Human Eye: Structure and Function, pp. 411–446. Sunderland, MA: Sinauer Associates.

Glossary

Cycles per degree – The number of complete phases of a grating (e.g., the distance between the center of a white bar and the center of the next bright bar in a square-wave grating; or the distance between two adjacent areas of maximum brightness on a sine-wave grating) contained in 1 of visual angle.

Minimum angle of resolution – The size of the angle subtended at the eye of the smallest feature which can be reliably identified on an optotype. Minute of arc – One-sixtieth of a degree. Optotype – A letter, symbol, or other figure presented at a controlled size to measure vision. Visual angle – The angle, which a viewed object subtends at the eye.

Detection and Resolution Acuity

Visual acuity can be defined in two broad ways. Detection acuity is measured by determining the size of the smallest object which can be reliably seen (is there a circle on the first or second screen?). Detection can be elicited reliably with targets, which subtend an angle at the eye as small as 1 s of arc (1/3600 ). Even a small point of light will stimulate several photoreceptors due to the point-spread function of the eye: that is, the way in which light is diffracted through the eye’s optics (Figure 1(a)).

Tests that require the identification of a target are a measurement of resolution acuity. These tests frequently involve identifying a letter or reporting an object’s orientation (what direction is this letter C facing?). Acuity for these tests depends on the separation of the target features: if they are too close, the point-spread function from each element will overlap and they will not be identified (Figure 1(b)). The smallest separation of the elements required for identification of the target (Figure 1(c)) is known as the minimum angle of resolution (MAR). For an adult observer with good vision, a typical MAR for a centrally presented, high-contrast target can be as good as 30 s of arc (1/120 ). Figure 2 shows the feature critical for the MAR for some commonly used tests of visual acuity.

Measurement of Visual Acuity

Visual acuity tests have been used for millennia: the ancient Egyptians are reported to have used discrimination of the twin stars of Mizar and Alcor as a measurement of vision. The most familiar clinical test of visual acuity, the Snellen chart, was introduced in 1862, and is still widely used today.

Detection acuity is often measured psychophysically by means of a temporal two-alternative forced-choice experiment (did the light appear in the first or the second interval?). Detection acuity is rarely measured clinically.

In psychophysical experiments of the visual system, resolution acuity is commonly measured by asking observers to report the orientation of a grating with variable separation between each dark and light bar (Figure 2(b)). In clinical practice, gratings are rarely used, with the exception of forced-choice preferential looking tests in preverbal children. These tests consist of a uniform gray field with an isoluminant grating toward one side of the chart (Figure 3(a)). In a featureless room, the test is presented to the child and the clinician observes whether the child looks toward the grating. The finest grating toward which the child repeatedly looks is recorded as the visual acuity.

For cooperative patients, optotypes are more often used to measure clinical resolution acuity. The Landolt C (Figure 2(c)) is the standard to which letter visual acuity tests are compared. This target consists of a ring of fixed width with a gap, of height equal to the stroke width, at the top, left, right, or bottom of the circle. The observer is asked to report the position of this gap. The smallest gap whose position can be reliably reported is equivalent to the MAR.

The National Academy of Sciences standard for visual acuity measurement advocates the presentation of 10 optotypes, of equivalent difficulty to the Landolt C, at each acuity size. The horizontal spacing between each optotype should be at least one character width, and vertical spacing between lines should be 1–2 times the height of the larger optotypes. It suggests that the number of characters on each line should be equal, and that the size difference between consecutive lines is 0.1 log units: in other words, for each target size, the next line should be approximately 1.26 times smaller.

The Snellen chart (Figure 3(b)) does not meet these recommendations: the number of letters per line and step size between the lines are variable, as is the horizontal and

Target

2-D PSF

1-D

PSF

Figure 1 Schematic illustration of the point-spread function of three visual targets: (a) a point target; (b) two adjacent lines, too close to be resolved; and (c) two adjacent lines, with sufficient separation to be resolved. Middle row: two-dimensional representation of the target point-spread function; bottom row: one-dimensional representation of the point-spread function; and red line indicates the sum of energy incident on the retina. PSF, point-spread function.

θ

(a)

θ

(b)

θ

(c)

θ

(d)

Figure 2 Examples of the limiting feature for four commonly used resolution tasks: (a) two-point discrimination task; (b) grating; (c) Landolt C; and (d) Sloan letter E (note that white gap size is equal in width to black bar elements).

vertical spacing on the chart. There is also a marked difference in the legibility of different letters on the Snellen chart: a W, for example, has far less separation between the elements of the letter and is more difficult

(a)

Figure 3 (a) A forced-choice preferential looking test consisting of a grating against an isoluminant background. Note the peephole in the center for the clinician to observe the child’s visual behavior; (b) the Snellen chart; and (c) The ETDRS chart. ETDRS, Early treatment of diabetic retinopathy study.

to identify than a letter L. In the 1950s, Sloan suggested the use of 10 letters with a selection of vertical, horizontal, oblique, and round strokes which are each about as legible as a Landolt C. These Sloan letters are C, D, H, K, N, O, R, S, V, and Z. Each of the Sloan letters has a stroke width of the MAR and has a total height and width of five times the MAR.

The Bailey–Lovie chart, introduced before the recommendations of the National Academy of Sciences, conforms to most of these requirements, although it only has five letters per line. Further, the letters on the Bailey–Lovie chart are taller than they are wide: their height-to-width ratio is 5:4 and they are selected from the British Standards set of letters (D, E, F, H, N, P, U, V, R, and Z). The ETDRS chart (Figure 3(c)), developed for the early treatment of diabetic retinopathy study (ETDRS), is similar in design but does use the recommended 5 5 Sloan letters.

A criterion of 7/10 letters being read correctly for a line to be marked as seen was suggested by the National Academy of Sciences. This threshold reduces the chance of the line being scored correctly by chance (by a blind observer) to around 1 in 9 000 000. On a chart with five letters per line, recording a visual acuity where four of the five letters are read correctly equates to a chance success rate of 1 in 46 000. There is a theoretical advantage if the observer knows there are only 10 letters which can be presented on the chart: if an observer guesses from all 26 letters rather than the ten Sloan letters, the probability of the observer getting four out of five letters correct reduces to about 1 in 100 000.