Ординатура / Офтальмология / Английские материалы / Ocular Disease Mechanisms and Management_Levin, Albert_2010

lacking palisade endings (potential proprioceptive innervation).6,30,31 In general, lack of representative muscle samples from human surgery hampers progress.29 Primary pathologies may also be found at the level of the motor nerve, e.g., neuropathies or disorders of the neuromuscular junction. Within the brain, specific pathologies may reflect developmental (agenesis of motor nuclei) or acquired conditions (brain lesions due to stroke, trauma, or disease such as multiple sclerosis). The cortex may show alterations due to abnormal circuitry for binocular vision, making it difficult to distinguish between primary cause and secondary adaptation. In Graves’ disease (hyperthyroidism), shared epitopes between orbital fibroblasts, extraocular muscles, and the thyroid may lead to interstitial edema and enlarged extraocular muscles that are infiltrated with inflammatory cells (see Chapter 56). In Duane retraction syndrome, the abducens nucleus and nerve are absent or hypoplastic, and the lateral rectus muscle is innervated by a branch of the oculomotor nerve (see Chapter 57). In the autoimmune disease myas­ thenia gravis, circulating antibodies lead to a reduced number of acetylcholine receptors in neuromuscular junctions, reducing the safety factor and extraocular muscle function.32

Etiology

Environmental and genetic risk factors

Fetal alcohol syndrome and fetal hydantoin syndrome22 as well as prematurity and perinatal hypoxia are risk factors for infantile esotropia.33 Major risks are listed in Table 59.1 and include Down syndrome, Duane’s retraction syndrome, and congenital fibrosis of the extraocular muscles (CFEOM), caused by mutations of genes that regulate oculomotor neuron development and axonal transport or guidance.8 Nevertheless, the etiology and pathophysiology of strabismus are unclear in the large majority of cases.

Other causes

Major categories of conditions that cause strabismus along the sensorimotor loop are compiled and illustrated in Figure 59.3. It is important to emphasize the circular nature and interdependencies between the motor and sensory loops: any disruption along this circle may cause derailment of binocular vision (Box 59.2). Disruption at multiple sites may have additive effects to surpass a critical threshold, possibly explaining the multifactorial inheritance pattern. Strabismus may result from etiologies that can be broadly grouped as “developmental” or “acquired” (Table 59.1). Developmental or early-onset forms of strabismus may be caused by abnormal maturation of binocular horizontal connections in the striate visual cortex.3,5,24 Later-onset forms of childhood strabismus may be caused by uncorrected hyperopia (far-sightedness) or weak fusional reflexes. Acquired strabismus may result from damage to the brainstem (internuclear ophthalmoplegia) or damage to the cranial nerves as a result of trauma, tumor, or strokes (paretic strabismus), interference with neuromuscular synaptic transmission (myasthenia gravis), alteration of the extraocular muscles (thyroid ophthalmopathy), or direct damage to the extraocular muscles, orbital tissues, or pulley systems (orbital

Pathophysiology

Figure 59.3  Synopsis of the circular, sequential flow of information between the eye and the brain for eye alignment and binocular vision. Eye positioning, visual input, generation of motor commands, and motor output constitute an interdependent circle that can be disrupted at each of the locations, as listed from 1 to 12. Cb, cerebellum; EOM, extraocular muscle; FEF, frontal eye field; LGN, lateral geniculate nucleus; MIF, multiply innervated fiber; MLF, medial longitudinal fasciculus; MT, medial temporal area; ODC, ocular dominance column; SC, superior colliculus; SIF, singly innervated fiber; SN, substantia nigra; Vest, vestibular nuclei. (Modified from Tychsen L. Infantile esotropia: current neurophysiologic concepts. In: Rosenbaum AL, Santiago AP (eds) Clinical Strabismus Management. Philadelphia: Saunders, 1999:117−138; Büttner-Ennever JA. Anatomy of the oculomotor system. Dev Ophthalmol 2007;40:1−14; and Goldberg ME. The control of gaze. In: Kandel ER, Schwartz JH, Jessell TM (eds) Principles of Neural Science, 4th edn. New York: McGraw-Hill, 2000:782−800.)

Box 59.2  Multiple causes of strabismus

Strabismus can be caused by a large number of primary causes along an interdependent sensorimotor loop that operates in a circular fashion

fractures). Major specific causes of strabismus are listed in Table 59.3.

Pathophysiology

Biological basis of the disease

Strabismus has unique pathophysiological features. Multiple, highly diverse primary causes contribute to strabismus. The resulting visual misalignment interferes, especially in the developing infant, with the reinforcing intrinsic mechanisms that normally lead to fused images and binocular vision. Finally, this vicious cycle invokes secondary, generally maladaptive responses that lock in the disturbance of binocular vision. We will discuss the presumptive sequence of events in detail, with an emphasis on trophic feedback mechanisms of circuit development and maintenance.

Section 8  Pediatrics Chapter 59  Strabismus

Deficiencies in optic radiations/tract/optic nerve (hypoplasia) or thalamus

Abnormal retinal circuitry/retinoblastoma

Defects (refractive errors) in the optic apparatus (lens/ cornea): cataract /astigmatism

Alignment of the eyes for binocular vision requires that each of the crucial relays and links in a complex series of neural circuits works smoothly and precisely, from the eye to the visual cortex (sensory loop), and via motor relay stations to the eye muscles (motor loop) (Figure 59.3). Any imbalance or disruption along this pathway can cause the system to malfunction, resulting in strabismus. Naturally, the system is most vulnerable during its development, when during a critical period stereoacuity develops34 and the crucial binocular neuronal connections form in the visual cortex.35 The normal retinal disparity can be used for depth perception. Whether images on the fovea of each eye are interpreted as a fused image or give rise to diplopia depends on the precise visual optics (whether the fixation points fall within Panum’s area; Figure 59.4) and the visual projections to cortex. A small deviation in the highly complex eye-posi- tioning feedback system can disrupt the fine balance and place the image “out of range,” giving rise to diplopia and suppressing the image from the weaker eye in the developing visual system.

Fixation Empirical

point horopter

Diplopia – Doubled image appears,

Diplopia – Doubled image appears,

‘nearer’ than fixation Vieth-Müller circle

Figure 59.4  The empirical horopter shows the range of binocular fusion, visual fixation points, and the optical basis of physiological and, by extension, pathophysiological double vision (diplopia). Panum’s fusional area (yellow) defines the zone of stereo vision. When images fall outside Panum’s area, diplopia results (green). The mathematically determined Vieth−Müller circle passes through the optical centers of each eye and the points of fixation. (Modified from American Academy of Ophthalmology. Pediatric Ophthalmology and Strabismus, Section 6, Basic and Clinical Science Course. San Francisco, CA: American Academy of Ophthalmology, 2007.)

tion can have a variety of primary causes. It may be a deficit that is intrinsic to that muscle, or the muscle may not receive proper commands from motor neurons, or there may be defects further upstream in the brain that compromise afferent input to the “phasic” and/or “tonic” motor neurons.36,37 There has been much controversy about the primary causes of strabismus (Table 59.3).4,5

Due to the circular processing (Figure 59.3), it can be difficult to assess which defect is primary, and which processes represent secondary (mal)adaptations, since muscles are altered in response to demand.28,29 To some extent, the brain can even reorganize its retinal orientation to compensate for ocular misalignment (“anomalous retinal correspondence”).9 Some investigators emphasize cortical lesions and their association with strabismus and suggest that such dysfunctional cortical development is causative.3,5 On the other hand, the fact that manipulations of the periphery (surgery of the eye muscles without any direct effect on the brain) can cure strabismus suggests that the brain circuits are principally intact and points to the eye muscles as the primary site.6 Minor, but important manipulations along the circular processing route may suffice to nudge − and subsequently maintain − the fused images within Panum’s area, thus restoring the system to work within a functional range (Figure 59.4).

Primary causes and secondary adaptations

It is often stated that malfunction of one or more eye muscles causes strabismus. However, the reason for such malfunc-

A trophic theory of strabismus

We emphasize an interdependency and multilevel communication between the motor command centers, the motor

Box 59.3  Strabismus and trophic signals

A unifying link of some strabismus syndromes may be defects in the processing of trophic signals that regulate muscle strength as well as neural circuit development and maintenance

pathway (to eye muscles) and the sensory pathway (from the eye), and the binocular visual processing in the cortex (Figure 59.3). We propose that this interdependency between neural circuits and their effector organ is mediated, at least in part, by trophic factors or trophic signals that move both anterogradely and retrogradely along axons.38–40 Such trophic mechanisms regulate the development of ocular dominance columns in visual cortex,39 and appear to affect binocular visual circuitry as well as regulation of contractile force of extraocular muscles.41,42 We postulate that these trophic signals are an essential part of a feedback system that precisely regulates eye movements which ultimately allow the fusion of the images from both eyes in the cortex (Box 59.3). Interestingly, several congenital forms of strabismus are linked to molecules involved in either the internalization (dynamins) or transport (kinesins) of proteins along axons, including the transport of trophic factors.8,43 Thus, a unifying link of strabismus syndromes may be defects in the processing, transport, and delivery of plasticity signals (trophic factors) that regulate muscle strength,41,42,44 motor neuron survival,43 afferent motor commands, ocular dominance columns, binocular circuits, and synaptic plasticity.39

Biological basis of the treatment

Multiple conditions along the motor and sensory routes can contribute to derail the alignment of images from the two eyes (Figure 59.3). If the alignment is near threshold, a small additional dysfunction may prevent fusion (Figure 59.4). Without fusion, there may be no “trophic reward” or reinforcement to maintain the connectivity between binocular neurons at the cortical level, and as a result, the downstream pathways are not strengthened or stabilized, exacerbating the vicious cycle (Figure 59.3). When the system is manipulated at the level of the eye muscles to restore normal eye alignment, then fusion may be achieved. The system can then acquire and stabilize the single fused image within the normal range of binocular vision (Panum’s area) and maintain the new alignment (Figure 59.4). Despite their limitations, research studies using animal models have rendered valuable new insights (Table 59.4).

How does surgery work?

By classical explanation, the surgeon creates either slack (recession) or increased tension (resection) in the muscle that is operated on. However, altering the length–tension relationship of the muscle does not account for all observed effects.45 Many quantitative characteristics of recessions are better explained by a torque vector model, instead of the classical length–tension model, consistent with the relevance of muscle pulleys (fibroelastic sleeves).46–48 This new understanding of the mechanics of ocular motility mechanics has implications for surgical techniques to correct ocular motility disorders.45,46

Pathophysiology

Table 59.4  Animal models for strabismus and extraocular muscle (EOM) research

How does botulinum toxin work?

Botulinum toxin acts by transient chemical denervation. This weakens an overacting muscle. The apparent paradox is that the therapeutic effect can be permanent, even though the effect of the toxin and the denervation lasts only 3−4 months. Initial studies indicated that the toxin’s long-term beneficial effects were due to a permanent alteration of one specific type of (developing) extraocular myofiber.6,49 However, developing extraocular muscles fully recover within 3−4 months after botulinum toxin treatment, without any residual loss of contractile force or any permanent structural alteration.19,50 The new data favor a central “reset” hypothesis which postulates that, once the system is realigned (by muscle lengthening19), even for a brief period, then the altered feedback can reinforce and engage the intrinsic brain mechanisms that support and stabilize visual alignment, achieving binocular fusion in the long term.50

How does orthoptics/vision therapy work?

Nonsurgical management of strabismus seeks to sharpen the retinal image by prescribing the appropriate spectacle correction and treating amblyopia. This provides an improved stimulus for fusion and reduces accommodative convergence. Orthoptics (eye exercises) can increase fusional amplitudes. This technique is especially effective for convergence insufficiency.2 Vision therapy can reduce suppression and make the patient aware of diplopia, potentially increasing fusional control. However, this increases the risk of making a patient permanently diplopic if fusional potential is lacking.2

Mutations

Genetics has an important role in identifying pathophy­ siological processes at the molecular level. Some gene mutations are responsible for defects in development and connectivity of oculomotor neurons8 (Figure 59.3, Box 59.4). If a crucial circuit (such as a population of cranial

Box 59.4  Strabismus and gene mutations

Several congenital strabismus syndromes are caused by mutations of genes that regulate the development of motoneurons which innervate extraocular muscles

nerve nuclei) is missing (rather than simply malfunctioning because of inappropriate input or stimulation), then that defect is much more difficult to rectify.

Conclusion

Considerable progress has been made with new imaging techniques13 and with the identification of some of the molecular players responsible for congenital strabismus.8

Screening for such risk factors (inherited genes) will be possible in the future. Since the importance of early diagnosis and rapid treatment has been established, systematic earlychildhood screening, including genetic testing, will be beneficial. Combined use of multiple treatment modalities such as botulinum toxin and trophic factors along with surgery may improve the precision of strabismus surgeries and predictability of outcome, potentially improving sensory fusion and reducing the need for reoperations. Larger-scale studies are needed that compare the long-term success and outcomes of different treatment options.

Acknowledgments

Our own research was supported by NIH grants EY 12841, EY 14405, NS 35931, and HD 29177.

2.von Noorden GK, Campos EC. Binocular Vision and Ocular Motility. Theory and Management of Strabismus, 6th edn. St. Louis: Mosby, 2002.

3.Tychsen LF. Strabismus: the scientific basis. In: Taylor DH, Hoyt CS (eds) Pediatric Ophthalmology and Strabismus, 3rd edn. Edinburgh: Elsevier-Saunders, 2005:836–848.

4.von Noorden GK. The History of Strabismology. Hirschberg History of Ophthalmology: The Monographs, vol. 9. Ostend, Belgium: JP Wayenborgh, 2002.

5.Tychsen L. Infantile esotropia: current neurophysiologic concepts. In: Rosenbaum AL, Santiago AP (eds) Clinical Strabismus Management. Philadelphia: Saunders, 1999:117–138.

6.Porter JD, Baker RS, Ragusa RJ, et al. Extraocular muscles: basic and clinical

aspects of structure and function. Surv Ophthalmol 1995;39:451–484.

8.Engle EC. The genetic basis of complex strabismus. Pediatr Res 2006;59:343– 348.

9.Wright KW. Pediatric Ophthalmology and Strabismus. St. Louis: Mosby, 1995.

10.von Noorden GK. Atlas of Strabismus, 4th edn. St. Louis: Mosby, 1983.

19.McNeer KW, Magoon EH, Scott AB. Chemodenervation therapy: technique and indications. In: Rosenbaum AL, Santiago PS (eds) Clinical Strabismus Management. Philadelphia: WB Saunders, 1999:423–432.

21.Parks MM. Atlas of Strabismus Surgery. Philadelphia, PA: Harper and Row, 1983.

22.American Academy of Ophthalmology. Pediatric Ophthalmology and Strabismus, Section 6, Basic and Clinical

Science Course. San Francisco, CA: American Academy of Ophthalmology, 2007.

23.Wright KW, Edelman PM, McVey JH,

et al. High-grade stereoacuity after early surgery for congenital esotropia. Arch Ophthalmol 1994;112:913–919.

25.Wright KW. Color Atlas of Strabismus Surgery. Philadelphia: JB Lippincott, 1991.

29.Spencer RF, Porter JD. Biological organization of the extraocular muscles. Prog Brain Res 2006;151:43–80.

33.Rosenbaum AL, Santiago PS. Clinical Strabismus Management. Philadelphia: WB Saunders, 1999.

Albinism refers to a heterogeneous group of hypopigmentation disorders that share an absolute or relative inherited deficiency of the pigment melanin that leads to characteristic changes in the skin, hair, and visual system (eyes and optic tracts). Melanin is produced and contained within melanosomes, intracellular organelles that are present in the stratum basale of the epidermis, hair bulbs, and intraocular epithelia. Most individuals with albinism have a simple, or nonsyndromic, form that affects the visual system, hair, and skin (oculocutaneous albinism, OCA) or mainly the visual system (ocular albinism, OA). Less commonly, individuals may have a complex, or syndromic, form of albinism that includes a distinctive pattern of organ involvement in addition to OCA. In recent years, much progress has been made in understanding the clinical features, pathophysiology, and molecular basis of albinism (Box 60.1).

perception may be poor; typically no stereopsis is demonstrated. Strabismus is common, with esotropia more frequent that exotropia. High refractive errors are common in albinism,1 apparently from failure of emmetropization.4 In children with albinism, the ophthalmologist must be alert to amblyopia superimposed on the acuity deficit directly related to the foveal hypoplasia. In a child with albinism, as in other children, asymmetric acuity should alert the ophthalmologist to possible amblyopia associated with strabismus or with difference in refractive error between right and left eye, anisometropia.

The lack of the protective effect of melanin in the eye underlies photophobia. The individual with albinism is also at risk for sunburn rather than tanning, and for malignancies of the skin, especially if exposed unprotected to intense tropical sun.

Individuals with albinism are typically fair of skin and hair and have hypopigmentation of ocular structures (Figure 60.1). The degree of cutaneous hypopigmentation can vary greatly, ranging from the classic image of the albino with white hair, white skin, and pink-red irides to one in which no apparent cutaneous hypopigmentation is present. More constant are the effects that albinism has on the eye and visual pathways. Consequently, examination of the eyes remains an essential step for the diagnosis of albinism.

The key ocular symptoms and signs are intimately related (Table 60.1). Deficits in iris pigmentation typically impart a gray or blue color to the irides, which transilluminate light (Figure 60.2A and B). Foveal hypoplasia and mild optic nerve hypoplasia are typical (Figure 60.2C), as is nystagmus. The foveal reflex is almost always absent. The ocular fundi appear pale with the choroidal vasculature visible through the neurosensory retina and retinal pigment epithelium (Figure 60.2D). Strabismus and high refractive errors are common (Box 60.2).1

Acuity is low, ranging from a legal blind level to only mild acuity deficits; median acuity is often cited as approximately 20/60. The low acuity is secondary to foveal hypoplasia2,3; nystagmus may also degrade acuity. Anomalous head posture is used to counteract the effects of the nystagmus. Depth

From biblical times albinism has been recognized; it has been argued that Noah was an albino (Box 60.3).5 There is a long, anecdotal history of albinism throughout the animal kingdom with notable ocular features.6 Foveal hypoplasia was recognized and documented histologically by Elschnig7 and a paucity of nondecussated fibers at the chiasm was reported in classical studies of the visual system in albino animals.8 In human subjects with albinism, electrophysiological9,10 and, more recently, functional magnetic resonance imaging11,12 studies have demonstrated anomalous organization of the visual pathways.

For many years albinism was classified on a biochemical basis as tyrosinase-positive or tyrosinase-negative in the hair bulb incubation test. However, this test is seldom performed today because of its lack of sensitivity and specificity, giving rise to many false negatives and false positives; for example, patients with OCA1B and OCA2 have different genetic bases for their albinism, but both yield tyrosinase-positive results in the hair bulb test. Conversely, OCA1A and OCA1B are caused by the same gene but give rise to tyrosinase-negative and tyrosinase-positive results, respectively.

Gradually the genetic foundation for the simple forms of albinism has been established.13 Four autosomal-recessive genes for OCA and one gene for X-linked OA have been

Box 60.1  Overview

•Albinism is a heterogeneous group of disorders

•Melanin pigment is deficient in all forms of albinism

•Hypopigmentation affects the eyes, skin, and hair to varying degrees

•Identification of ocular features is essential for the diagnosis of albinism

Table 60.1  Ocular features of albinism

Low acuity

Nystagmus

High refractive errors

Strabismus

Irides that transilluminate light

Foveal hypoplasia

Fundus hypopigmentation

Photophobia

Box 60.2  Common ocular features

•Low visual acuity

•Nystagmus

•Iris sites that transilluminate light

•Foveal hypoplasia

•Hypopigmented fundi

•Strabismus

•High refractive errors

Box 60.4  Diagnostic workup

•Identify ocular features

•Evaluate visual pathways

•Genetic testing

•If clinically indicated, evaluate for complex forms

Box 60.3  History

•Albinism has been recognized since biblical times

•Structural and functional anomalies of the visual pathways have been substantiated

•Molecular genetic basis for simple and complex forms of albinism has been delineated

identified (Table 60.2). OCA types 1–4 are inherited with equal frequency in males and females. The recurrence risk to couples with an affected child is 25% with each pregnancy. The ophthalmic characteristics of OCA1–4 are listed in Table 60.1. OA1 follows an X-linked pattern of inheritance with affected hemizygous males, and female carriers who have healthy eyes, normal vision, and uneven fundus pigmentation (Figure 60.2E). Males with OA share essentially the same ophthalmic characteristics of those with OCA. All daughters of fathers with X-linked OA are obligate carriers, and carriers have a 50% chance of having an affected son (or carrier daughter) with each pregnancy.

The genetic basis has also been determined for a number of complex forms of albinism that have systemic comorbidities (Table 60.2). In contrast, the simple forms of albinism (Table 60.2) do not lead to systemic comorbidities.

The overall frequency of albinism in the general population is estimated to be 1 in 17 000, and about 1 in 65 individuals is a carrier for OCA. The frequency varies with specific type (Table 60.2) and with ethnicity. An estimated 18 000 individuals in the USA have a form of albinism. OCA1 and OCA2 are the two most common forms of albinism and occur with similar frequencies.

Diagnostic workup

A history of nystagmus, decreased visual acuity, and fair skin and hair within the family group raises the suspicion for albinism (Box 60.4). Inspection of the ocular structures adds diagnostic information. Typically, the irides transilluminate light (Figure 60.2A and 60.2B). Foveal hypoplasia and albinotic fundi (Figure 60.2c and 60.2D) are the main fundus features; mild optic nerve hypoplasia may also be present.14 The optic nerve head in children with albinism is significantly smaller than in normally pigmented, age-similar children, being about 80% of the normal mean diameter (AB Fulton, personal observation).

Box 60.5  Differential diagnosis

Simple forms of albinism

•OCA1

•OCA2

•OCA3

•OCA4

•OA1

Complex forms of albinism

•Hermansky–Pudlak syndrome

•Prader–Willi syndrome

•Angelman syndrome

•Chédiak–Higashi syndrome

Other disorders with hypopigmentation

•Waardenburg syndrome

•Piebaldism

•Vitiligo

•Griscelli syndrome

We favor an attempt at genotyping to secure a specific diagnosis of albinism, which is important for genetic counseling and anticipatory guidance. Complex forms of albinism, e.g., Hermansky–Pudlak syndrome, can be mistaken for OCA but have important medical complications. These syndromic forms are virtually excluded if a genetic diagnosis of OCA or OA is secured (Table 60.2). Other hypopigmentation syndromes that do not share all of the cardinal features of albinism (e.g., eye and optic tract) can also be excluded with a genetic diagnosis. However, even in dedicated laboratories, a genetic diagnosis of albinism is currently achieved in only about half of the patients who have a wellsubstantiated clinical diagnosis.15 This may improve with the recent availability of more comprehensive clinical testing for OCA1 and OCA2. In individuals with nystagmus and foveal hypoplasia, the diagnosis of albinism may pertain even if there is no obvious hypopigmentation.16 Thus, there is no ignoring the importance of the ophthalmic examination.

Differential diagnosis

Differentiation of the several types of albinism depends on history, and ideally, a genetic diagnosis (Table 60.2; Box 60.5). The ocular features are similar across the various types; OCA1A has the most pronounced hypopigmentation, but there is considerable overlap of the phenotype among

the several types of albinism (Table 60.2). Complex forms of albinism share ocular features of albinism but also include other systemic findings such as bleeding diatheses (Hermansky–Pudlak syndrome), severe cognitive impairment (Prader–Willi and Angelman syndromes), and immunodeficiency (Chédiak–Higashi syndrome). Other individuals with syndromic hypopigmentation are not clinically considered albinos because they do not have the requisite ocular features. These include Waardenburg syndrome, piebaldism, vitiligo, and Griscelli syndrome.

Some previously described forms of albinism now appear to be related to unusual presentations of OCA or OA. For example, autosomal-recessive OA has in most cases been shown to be due to a mild form of OCA with inconspicuous cutaneous involvement. In one study, 56% of 36 unrelated Caucasian individuals diagnosed with autosomal-recessive OA were found genetically to have OCA1 or OCA2, and almost all of the OCA1 cases were heterozygous for one severe mutation and one temperature-sensitive R402Q

mutation.17 Autosomal-recessive OA and deafness have been shown in one extended family to be caused by digenic inheritance of mutations in the microphthalmia-associated transcription factor (MITF) gene (causing Waardenburg syndrome type II) and in the tyrosinase gene (causing OCA1), whose expression MITF controls.18 Autosomal-recessive OCA and deafness were shown to be coincidental in one family, caused by co-inheritance of mutations in the connexin 26 gene and the OCA4 gene.19 X-linked OA and late-onset neurosensory deafness map to the same locus as the OA1 gene and likely represent an allelic variant or a contiguous gene syndrome.

Treatment

Management is supportive rather than curative. Protection of the skin and eyes from excessive light reduces the risk of photic damage to these organs (Box 60.6). For eye protection, hats or caps with visors and dark glasses are advisable.