Pediatric Ophthalmology in the setting of developmental disability.

Visual impairment in infants and children with developmental disabilities.

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Abstract

If the visual system does not receive clear images from well-aligned eyes during childhood, the ability to develop normal binocular vision is lost permanently. Therefore, proper assessment and treatment of visual disorders in childhood can have a profound influence on life-long visual function. For instance, childhood refractive correction, optical treatment of visual deprivation or suppression (amblyopia), removal of media opacities such as congenital cataracts, and laser treatment to prevent retinal detachments in premature babies are some of the most effective treatments in all of medicine.

The fundamentals of visual assessment and treatment in the developmentally disabled are the same as for all children. Proper assessment of the red reflex, eye alignment, ocular motility, visual acuity, stereopsis, and pupils will result in appropriate ophthalmologic referrals. Timely treatment of retinopathy of prematurity, refractive errors, cataracts, amblyopia, and strabismus can have a lifelong impact on ultimate visual outcome. Numerous developmental disorders affect both the neurologic and visual systems. Therefore, ophthalmologic disorders are more common in the developmentally disabled, and and a baseline assessment by an ophthalmologist is essential. Whenever there is doubt about the proper functioning of the visual system, an ophthalmologic evaluation is warranted.

 

Visual impairment in infants and children with developmental disabilities:  a review of pediatric ophthalmology.

Christopher T. Leffler, MD, MPH

If the visual system does not receive clear images from well-aligned eyes during childhood, the ability to develop normal binocular vision is lost permanently. Therefore, proper assessment and treatment of visual disorders in childhood can have a profound influence on life-long visual function. For instance, childhood refractive correction, optical treatment of visual deprivation or suppression (amblyopia), removal of media opacities such as congenital cataracts, and laser treatment to prevent retinal detachments in premature babies are some of the most effective treatments in all of medicine.

Although the fundamentals of visual assessment and treatment are the same for all children, those with developmental disabilities present particular challenges. The assessment relies more heavily on objective tests when verbal feedback is limited or delayed. It may not be clear to caregivers whether functional problems are due to disorders in the visual, neurologic, other, or multiple systems. Some procedures, including eye examinations, must be done under general anesthesia, and more precautions must be taken after surgery to protect the eyes.

This chapter describes the assessment, criteria for ophthalmologic referral, and overview of treatment options for visual disorders in children, while highlighting aspects relevant to the developmentally disabled.

Visual Anatomy and Physiology.

The primary refractive element of the eye is the air-tear interface, the power of which is determined by the corneal curvature. While traversing the aqueous-filled anterior segment, light passes through the pupillary aperture, the size of which is determined largely by the ambient light level. Light is then refracted by the crystalline lens. The power of the lens is adjusted by the accommodative mechanism so that the target image is focused on the retina. After passing through the clear vitreous and inner layers of the retina, the light is absorbed by the outer retinal photoreceptor elements, consisting of rods and cones. Rods are relatively more sensitive in low-light, or scotopic, conditions and are more numerous in the retinal periphery. Cones are concentrated in the center of the retina where the image is focused. There are three types of cones which have different absorption spectra to permit color perception. The photoreceptor signals are then transduced by intervening bipolar cells to activate ganglion cells, which have their cell bodies in the inner retina. The ganglion cell axons constitute the optic nerve and the optic tracts, which conduct the visual stimuli to the lateral geniculate body of the thalamus. Nasal optic nerve fibers, carrying information on the temporal visual field, cross at the optic chiasm. The post-chiasmal optic segments, termed the optic tracts, carry information on the contralateral visual field. The lateral geniculate nucleus sends information via the optic radiations to the primary visual cortex.

Assessment Of The Eye.

Pediatric eye examination requires principles generally relevant to childhood medical assessment. Examination must be opportunistic, and must progress from the least disturbing (observation at a distance, ability to fix and follow interesting targets) to the most noxious (indirect ophthalmoscopy, dilating drops) so that the maximum amount of information can be gleaned before the child stops cooperating. Observing the child while discussing the history with the family provides significant information about the level of attention, visual acuity, and intermittent ocular misalignment.

Timing of examinations.

Pediatricians begin evaluating the eye at birth (Table 1). Visual acuity testing with vision charts begins in the pediatrician’s office at least by age 3 (Table 1, Friedman 2003). Friedman and Kaufman have recommended routine comprehensive dilated eye examinations by a pediatric ophthalmologist at age four (2003). The rationale is to detect subtle disease which can be missed by nonophthalmologists at a time when visual deficits are still amenable to treatment. These authors also recommend routine follow up ophthalmology evaluations at least every 4 to 5 years. There is a consensus that examinations by a pediatric ophthalmologist are indicated in developmental disabilities, such as cerebral palsy (Ashwal 2004).

Visual acuity.

Visual acuity refers to the ability to resolve two closely spaced points. Visual acuity is denoted by a fraction, for which the numerator is the distance to the target, and the denominator is the distance at which a normal adult can distinguish the target features. For instance, 20/40 indicates that from 20 feet the patient can distinguish a target that a normal adult can discern from 40 feet. If the patient cannot see the largest target, which often corresponds with 20/400 vision, the target can be moved closer, or it can be noted whether the patient can count outstretched fingers (“count fingers vision”), can identify hand movement (“hand motions vision”), or can see light but not form (“light perception vision”).

Young children and some patients with disabilities cannot verbalize the identity of a visual target. Therefore, objective examination techniques are used to assess the level of vision. As noted above, observation while discussing the history often clarifies whether the child spontaneously fixates on faces or other targets of interest. A toy, brightly colored object, or penlight can be passed in front of the child to see if the child can fixate on and follow the target. If the child succeeds with both eyes open, each eye should be tested individually. The child may object more strenuously when one is covered compared with the other. This fixation preference suggests a difference in visual acuity between the eyes.

Optokinetic nystagmus is elicited by spinning a drum with vertical stripes to elicit slow horizontal ocular pursuit followed by rapid return saccades. Optokinetic nystagmus is tested at near, and corresponds with a vision of at least 20/200 to 20/400.

Babies and nonverbal patients can be tested by preferential looking techniques. Older children can be tested with a number of visual acuity charts which require progressively more sophisticated responses. The tumbling E chart has a series of letter E’s which the child identifies as being oriented “up, down, or to the side.” It is not useful to ask the child to distinguish orientation to the right or the left. Some children will not correctly describe the distant target, but can match it with an image on a near card. Some children will not be able to determine the orientation of the letter E, but can match the orientation of a picture of a hand with their own hand. Visual acuity charts with standardized shapes can be used. The child may need to be familiarized with the shape names at near. Older children and adults can be tested with the standard Snellen or other alphabetic charts. In general, it is helpful to use the method which requires the most sophisticated response that the child can muster. As children of the same age may vary in their verbal abilities, several charts may need to be tried. Although children are known to test better on average on the simpler tests, there is wide interindividual and intraindividual variation. In practice, the best reproducible response is used for clinical decisions, although all results are documented.

Referral to an ophthalmologist should be made if there is a two-line inter-eye difference in visual acuity, or if visual acuity is worse than 20/40 at ages 3 to 5 or worse than 20/30 at age 6 (Table 1).

Visual fields.

The peripheral visual field can be tested by confrontation, using the examiner’s visual field as a control. In current clinical practice, management decisions about glaucoma and other optic neuropathies are usually based on automated perimetry of the central 24 or 30 degrees. Automated perimetry of the more peripheral visual field is not reliable enough to be routinely useful. Testing of the more peripheral visual field is typically done with Goldmann kinetic perimetry, or using a manual wall-mounted tangent screen.

Visual impairment categories.

Visual impairment grading is important for determining qualification for social services and occupations, as well as the best low vision aids. Most schemes for categorizing visual impairment are based on visual acuity as well as the horizontal peripheral visual field. For instance, in the United States, legal blindness is defined as a corrected visual acuity of 20/200 or less, or a visual field of 20 degrees or less. Driving requirements vary from state to state and for whether driving is commercial or noncommercial. In the U.S., corrected visual acuity of 20/40 or better is required in both eyes for inter-state commercial driving. A low-vision specialist should be consulted when long-term severe visual impairment is expected. Of course, this assessment will consider aspects of visual function besides visual acuity and fields, such as accommodation, contrast sensitivity, and occupational or other visual needs.

Eye alignment.

Assessment of eye alignment begins simply by watching the child while interviewing the parents. Some ocular deviations will vary based on the direction of gaze, target distance, level of fatigue, or other factors. The child may not cooperate with attempts to elicit different gaze directions during the examination. Therefore, the more time spent watching the child, the better.

The examiner attempts to determine if both eyes are aligned on the same target. Ocular deviation may be medial (esotropia), lateral (exotropia), upward (hypertropia), or downward (hypotropia). At all ages, ocular alignment can be assessed by holding a penlight in front of the eyes and examining the reflection in the cornea, termed the corneal light reflex. Fixation on the penlight with either eye should result in a well-centered corneal light reflection in both eyes.

If the patient can fixate with both eyes, one can perform the cover test for a manifest deviation, termed a tropia. Here, the examiner simply covers the eye which appears to be fixating. If the other eye moves in any direction to fixate on the target, then that eye was indeed not previously fixating on the target and a tropia is present. One must test both eyes several times to be certain.

Sometimes no manifest deviation is present, but the patient has an underlying tendency for deviation, termed a phoria. The total deviation (phoria plus tropia) is elicited by the alternate cover test. One eye is covered to eliminate fusion, and the uncovered eye fixates on a target. Then the occluder is rapidly moved to the other eye. If the previously covered eye moves to fixate on the target, then a phoria, apparent only in the absence of fusion, is present. A small phoria may be a normal finding. However, if the family describes a tropia outside the office, then a phoria on alternate cover testing may represent an intermittent tropia, and referral decisions should be made as if a tropia were seen in the office.

Nystagmus.

Nystagmus, or rhythmic extraocular movements, may be either sensory or motor. Severe visual deprivation will result in nystagmus. Multiple inherited conditions are associated with nystagus (Table 2). Severe congenital nystagmus decreases foveation time, which lowers visual acuity. Medical, optical, or surgical treatments which reduce eye movement can improve visual acuity (Maybodi 2003). Retrobulbar or intramuscular botulinum toxin injection can reduce nystagmus amplitude, but for children or any developmentally disabled who cannot tolerate in-office procedures, the necessity for periodic reinjections makes this impractical. Horizontal rectus muscle recessions have been used successfully in children with no null point (Alio 2003), and recession/resection procedures are used if a null point is observed (Maybodi 2003, Pratt-Johnson 1991).

Spasmus nutans is a benign high frequency oscillation seen in young children associated with torticollis and head bobbing. The condition resolves spontaneously, but an MRI should be obtained to rule out chiasmal tumors.

Ophthalmoscopy.

Clarity of the ocular media is assessed at all ages with the red reflex test, in which an ophthalmoscope is used from a distance of a few feet and a red retinal reflection should be seen through the pupil. A dark red reflex may represent a severe refractive error, a very small pupil, strabismus, or cataract or other media opacity. A white red reflex may represent retinoblastoma or exudative retinal processes such as Coat’s disease. An abnormal red reflex requires a referral.

The direct ophthalmoscope can also be used in cooperative children to examine the fundus, including the optic nerve. The high magnification of the direct ophthalmoscope is associated with a narrow field which does not permit viewing in the presence of substantial eye movement. Therefore, ophthalmologists typically use the indirect ophthalmoscope to obtain a wide field view of the fundus even with uncooperative patients. Scleral depression with topical anesthesia is used to stabilize the eye and see the peripheral retina.

Pupils.

Constriction of the pupils in response to light occurs by a reflex arc which is present to some degree at 30 weeks gestational age and reliably at 34 weeks. Pupillary fibers leave the posterior portion of the optic tract to reach the midbrain at the level of the superior colliculus where they synapse in the pretectal nuclei. Efferent fibers from each pretectal nucleus pass to both the right and left Edinger-Westphal nuclei, with decussating fibers running both anterior and posterior (in the posterior commissure) to the cerebral aqueduct. Preganglionic parasympathetic fibers pass from the Edinger-Westphal nucleus via the inferior division of the third cranial (oculomotor) nerve to synapse in the ciliary ganglion of the orbit. The postganglionic short ciliary nerves include fibers for both iris constriction and ciliary muscle action (accommodation).

Of note, partial decussation of fibers in the optic chiasm and of fibers leading to the Edinger-Westphal nuclei results in equal efferent pupillomotor output to both eyes. Therefore, if a flashlight is passed quickly from one eye to the other, the direction of pupillary movement will be the same in both eyes. In other words, both eyes will either constrict, dilate, or remain unchanged. Only the last response is normal. Constriction of both eyes means that the afferent system of the second eye transmits a stronger impulse, and the first eye has a relative afferent pupillary defect. Dilation of both eyes means that the second eye has an afferent pupillary defect. An afferent pupillary defect always requires an ophthalmology referral. The most common cause of an afferent pupillary defect is optic nerve disease. Sometimes large amounts of retinal disease, dense media opacities (vitreous hemorrhage, but not cataract), or amblyopia can cause an afferent pupillary defect. When performing the swinging flashlight test, it is important to test in the dark and to hold the light in front of each eye long enough to permit system equilibration before rapidly swinging the light to the other eye.

Intraocular pressure.

The intraocular pressure is a universal measurement during adult ophthalmology visits, but the difficulty in obtaining the pressure in uncooperative patients makes it obtained less often in children. Pediatricians are not expected to routinely check the pressure, but it is reasonable to palpate the eye gently if there is a clinical question. Applanation tonometry at the slit lamp, the standard in adults, cannot be done in uncooperative patients. Therefore, the tonopen is routinely used in the office in children, although lid squeezing, crying, and moving may cause errors. During examination under anesthesia, the weighted Schiotz tonometer, Perkins applanation tonometry, or the tonopen can be used.

Congenital glaucoma produces symptoms of epiphora, photophobia, and blepharospasm. Any of these findings should prompt ophthalmologic referral if another cause is not obvious. Congenital glaucoma produces corneal edema, an enlarged eye (buphthalmos), elevated intraocular pressure, and optic disc cupping. The normal horizontal corneal diameter is 9.5-10.5 mm at birth, and 10-11.5 mm at age 1 year. Glaucoma is suggested by a horizontal corneal diameter more than 1 mm above these limits or in excess of 13 mm at any age (Simon 2004).

Electrophysiology.

Visual electrophysiology may be used to help determine the site and severity of visual disturbance. The electroretinogram records the electrical response of the retina to a bright flash of light or to an alternating checkerboard pattern. The size of the checkerboard producing a response can help assess the visual acuity. The visual evoked potential records the electroencephalographic response to visual stimulation. Visual electrophysiologic responses mature substantially during the first year, and especially the first six months, of life (Brecelj 2003, Edward 2003). Therefore, the laboratory must have experience with and knowledge of the expected responses with their protocol if infants are tested.

Pediatric ophthalmology findings.

A number of childhood eye disturbances are routine in pediatric ophthalmology. As many pediatric disorders have both ophthalmologic and neurologic effects (Table 2), visual disorders are even more common in multiple types of developmental disability.

Prematurity.

Prematurity is associated with both visual and neurologic impairment. The most devastating ophthalmologic complication is retinopathy of prematurity (ROP). The child is born before the retina is completely vascularized. The peripheral avascularized retina is presumably ischemic and secretes neovascular growth factors, including vascular endothelial growth factor (VEGF). Fibrovascular proliferation into the vitreous at the border of the vascularized and avascular retina leads to retinal detachment and therefore blindness. All infants under 1500 grams or of gestational age 30 weeks or less must be screened by the ophthalmologist for retinopathy of prematurity. The first examination is performed at 31 to 33 weeks postgestational age (AAP 2006). Retinal detachment can be prevented in many infants by ablation of the peripheral avascular retina with cryotherapy. More recently, peripheral retinal laser photocoagulation has been found to be effective and better tolerated. One major sign that ocular stress is severe enough to lead to retinal detachment is the presence of significant vascular tortuosity and dilatation, termed “plus” disease. The current criteria for laser treatment from the Early Treatment of ROP Study rely heavily on the presence of plus disease, although fibrovascular proliferation and posterior location of the avascular retinal border also play a role (Good 2004).

 
Bevacizumab (Avastin) is a monoclonal antibody which binds to VEGF.  The BEAT-ROP study was a trial which randomized premature infants with stage 3 “plus” disease to intravitreal bevacizumab injections or conventional laser therapy (Mintz-Hittner 2011).  Only 4% of infants treated with bevacizumab suffered a recurrence of retinopathy, compared with 22% in the laser-therapy group.  The trial was too small to assess safety, so additional data may be required before widespread adoption of bevacizumab therapy.

Lowering ambient light levels has been found not to affect the likelihood of retinopathy. In early randomized trials predating pulse oximetry, unrestricted oxygen administration was associated with higher rates of retinopathy of prematurity. In addition, inspired oxygen tensions over one half atmosphere cause pulmonary damage in people of any age. As a practical matter, one needs to provide enough oxygen to avoid peripheral ischemia, but not enough to cause pulmonary and possibly ocular damage. This issue was addressed empirically in the STOP-ROP study which compared conventional oxygen saturation (89% to 94%) with higher target saturation levels (96% to 99%) in premature infants with prethreshold retinopathy (STOP-ROP 2000). As one might expect, it was found that higher levels of oxygenation resulted in more cases of pulmonary complications, longer hospitalizations, and a higher mortality rate. There was no difference between the two groups in terms of the progression of retinopathy.

Premature babies are also more likely to have refractive errors, strabismus, and glaucoma. Therefore, they need to have regular eye examinations throughout childhood. Infant formulas containing two long-chain polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid, are now commercially available. The latter has been shown to result in better visual acuity, particularly in preterm infants (Carver 2003).

Refractive errors.

Significant refractive errors are quite common in the general pediatric population, and are found in over 40% of patients with intellectual disabilities (Warburg 2001, van Splunder 2003). Correction of refractive errors can have lifelong visual benefits. The pediatrician is not expected to perform refraction. Refraction can be performed even in nonverbal or young patients by retinoscopy with a skiascopy rack. In verbal patients, this refraction can be subjectively refined.

Amblyopia.

Amblyopia is a unilateral or bilateral decrease in visual acuity due to an absolute or relative abscence of a clear image, or due to strabismus, during the visual development period. Amblyopia is not associated with any anatomic findings on clinical examination. Amblyopia is found in approximately 2-4% of the North American population, and is highly treatable during the visual development period (Simon 2004). This period was historically regarded as ending at age 8, although a recent study has shown some visual acuity improvement can be attained at least through age 12, and possibly through age 17 (Scheiman 2005). Younger children have a higher probability of successful treatment. For instance, in a trial of patching for amblyopia, children age 5 or 6 improved 3.8 lines, while children age 3 or 4 improved 5.5 lines, nearly a 50% difference (Holmes 2003).

Initial treatment consists of refractive correction. If some degree of amblyopia persists, vision in the better eye is reduced by patching, by eliminating accommodation with atropine, or by optical blurring. By forcing the patient to use the amblyopic eye, treatment improves the ability to process visual input from this eye. Recent randomized studies have demonstrated that both atropine and patching are effective, and that patching regimens involving fewer hours during the day are effective (Holmes 2003). Finally, strabismus is corrected if present.

Strabismus.

Strabismus represents a misalignment of the eyes and can result in permanent loss of visual acuity or stereopsis. Most childhood strabismus is comitant, i.e. the deviation is the same in all directions of gaze. A small exotropia is present in many newborns, and usually disappears spontaneously as fusional mechanisms develop.

Comitant esotropia in childhood is typically divided into two major types: infantile and accommodative. Infantile esotropia onset is at age several months. The deviation may be large-angle, and is not typically associated with hyperopia. Correction requires strabismus surgery or botulinum toxin injection (McNeer 1997). Patients over age 4 months with constant large-angle (>40 prism diopters) esotropia without significant hyperopia can be considered for early surgery (Hutcheson 2004).

Accommodative esotropia occurs after one year of age and is associated with an intermittent angle, usually worse at near, and hyperopia. The accommodation required to obtain a clear image in the setting of hyperopia is associated with convergence. In some cases, the child is not unusually hyperopic, but accommodation is associated with an unusually high degree of near convergence. Accommodative esotropia is treated with refractive correction.

The above types of esotropia are not mutually exclusive. Some early-onset esotropia is associated with hyperopia, and refractive correction is a reasonable first step even though strabismus surgery may be necessary later. Likewise, surgery may be necessary to treat residual deviation after refractive correction of late-onset accommodative esotropia.

Cataract.

Congenital cataract is detected with the red reflex examination and requires immediate ophthalmologic referral. Cataracts are found in 8% to 54% of mentally retarded patients (Wu 2005) and are seen in many developmental conditions (Table 2). Childhood cataract morphology is related to the associated systemic condition (Table 2, Amaya 2003). Associated systemic disorders are usually apparent at the time of cataract evaluation. A TORCH titer (toxoplasmosis, rubella, cytomegalovirus, herpes simplex), RBC transferase, and galactokinase levels constitute the basic metabolic workup to rule out galactosemia and congenital infections. More extensive metabolic evaluation may be warranted in selected cases (Tesser 2005).

Surgical removal of severe congenital cataracts is indicated. Aphakic spectacles can be worn if cataracts are removed bilaterally. Comparison of optical correction with a contact lens versus intraocular lens implantation in cases of unilateral infantile cataract is the subject of the Infant Aphakia Treatment Study (Lambert 2003).  [The early results from this study indicate that at one year of age, the contact lens group and the primary intraocular lens group had similar visual acuity outcomes, but that the contact lens group required fewer surgeries (Infant 2010).]  Congenital cataract surgery may be associated with late-onset glaucoma.

Delayed visual maturation.

An apparently delayed ability to see despite the absence of other developmental delays is termed delayed visual maturation (Mercuri 1997). The family notices an inability to fixate on targets. A complete eye examination is indicated. Sometimes correction of hyperopia is associated with resolution. An MRI may be indicated to search for neurologic abnormalities. Visual electrophysiology can document the degree of function of the retina and optic nerve.

Retinal disorders.

A number of disorders associated with developmental delay or disability can produce retinal disease. Metabolic storage diseases result in accumulation of light-colored metabolic precursors in retinal ganglion cells surrouding the fovea, resulting in the appearance of a “cherry-red spot” in the macula (Table 2). Retinitis pigmentosa describes a group of inherited conditions which diffusely affect photoreceptor and pigment epithelial function resulting in visual field constriction and abnormal electroretinogram responses. Many causes of pigmentary retinopathy are associated with neurologic findings (Table 2). It is particularly important to diagnose treatable causes. Refsum’s disease, associated with high serum phytanic acid levels, is treated with a low phytanic acid and low phytol diet. Hereditary abetalipoproteinemia (Bassen-Kornzweig syndrome) is associated with decreased serum Apo-B levels and is treated with supplementation of vitamin A, E, and K and dietary fat restriction. Kearns-Sayre syndrome, associated with ptosis and ophthalmoplegia, may require a pacemaker to prevent atrioventricular block, and may benefit to some degree with coenzyme Q10 administration (Table 2). Congenital syphilis can be identified with standard treponemal serology.

Optic nerve disorders.

Optic atrophy is noted as optic nerve pallor, loss of the disc capillary net, or nerve fiber layer dropout. Any congenital or acquired process which damages the retinal ganglion cells or their axons can produce optic nerve atrophy. Compressive lesions, trauma, hydrocephalus, and hereditary conditions can cause optic atrophy. Associated disorders include cerebral palsy, retinitis pigmentosa, and metabolic storage diseases (Table 2).

Optic nerve hypoplasia consists of a unilateral or bilateral congenitally small optic nerve with a surrounding halo of scleral tissue. This yellow outer ring produces the so-called “double-ring sign.” The border of the inner ring represents the termination of the retinal pigment epithelium. The total size of the optic nerve plus the peripapillary halo is equal to the size of the normal optic disc. A poor foveal light reflex or vessel tortuosity may also be seen. Optic nerve hypoplasia is seen in multiple conditions, including septo-optic dysplasia (deMorsier syndrome), albinism, aniridia, and Aicardi syndrome (Table 2). Maternal gestational diabetes and maternal exposure to alcohol, phenytoin, and corticosteroids are also associated with optic nerve hypoplasia (Sergott 2005). Visual acuity is variable. In asymmetric cases, a portion of the vision drop may be amenable to amblyopia therapy. An MRI to evaluate for the midline brain structure of deMorsier syndrome is indicated. An endocrinologic evaluation is critical, as patients with deMorsier syndrome may have life-threatening pituitary abnormalities, as well as treatable growth hormone deficiency.

Conclusions.

The fundamentals of visual assessment and treatment in the developmentally disabled are the same as for all children. Proper assessment of the red reflex, eye alignment, ocular motility, visual acuity, stereopsis, and pupils will result in appropriate ophthalmologic referrals. Timely treatment of retinopathy of prematurity, refractive errors, cataracts, amblyopia, and strabismus can have a lifelong impact on ultimate visual outcome. Numerous developmental disorders affect both the neurologic and visual systems. Therefore, ophthalmologic disorders are more common in the developmentally disabled, and and a baseline assessment by an ophthalmologist is essential. Whenever there is doubt about the proper functioning of the visual system, an ophthalmologic evaluation is warranted.

References.

[References for the entire chapter are in the entry for Table 2.]
 
[This table is from: Leffler CT. Visual impairment. In: Accardo PJ (ed). Developmental disabilities in infancy and childhood. Johns Hopkins Univ. Press. Balto., MD 2007. pp 501-520.]

Table 1. Development and assessment of the eye.

Gestational Age.

22 days.                    Optic primordia appears.

Any birth.                  →Fundus checked for red reflex.
                                      →Corneal light reflex tested.
                                      →Cover test performed.

30 weeks.                 →Screening for retinopathy of prematurity by

                                         ophthalmologist required for gestational age <= 30

                                         weeks or birthweight < 1500 g.
                                     Pupillary light reflexes may be present. 
                                     Lid closure in response to light.

34 weeks.                Vestibular (doll’s head) eye rotations well-developed.

 

Term Age.

Birth.                         Visual fixation present. 
                                     Optokinetic nystagmus and conjugate horizontal gaze well-

                                            developed. 
                                    Visual acuity 20/400.

1 month.                   Pupillary light reflex well-developed.

2 months.                 Fixation and conjugate vertical gaze well-developed.

                                     Color vision present.

2-5 months.             Blink response to visual threat.

3 months.                 Visual following well-developed.

4 months.                 Accommodation well-developed. 
                                     Eyes should be well-aligned in the absence of pathology.

6 months.                 Color vision at adult level.

                                    Fusional convergence and iris stromal pigmentation

                                    well-developed.

                                    Stereopsis developed.

1 year.                         Visual acuity 20/50.

2 years.                         Acuity by grating preferential looking or Snellen chart at

                                        adult level (20/20). 
                                     →Check fundus with direct ophthalmoscope.

3 years.                     →Check visual acuity.

                                        Refer if <4 of 6 correct on 20-feet line with either eye

                                            tested at 10 feet (<10/20 or <20/40) (AAP 1996).
                                        Refer if 2-line difference between eyes (i.e. 10/12.5 and

                                                10/20, or 20/25 and 20/40) (AAP 1996).
                                    →Cover test at 10 feet. Refer for any eye movement

                                                (AAP 1996).
                                    →Random-dot-E stereo test at 40 cm (630 seconds of arc).

                                            Refer if <4 of 6 correct (AAP 1996).

6 years.                     →Check visual acuity.

                                            Refer if <4 of 6 correct on 15-ft line with either eye

                                            tested at 10 ft. (ie, <10/15 or <20/30) (AAP 1996).
                                            Refer if 2-line difference between eyes (ie, 10/10 and

                                                    10/15, or 20/20 and 20/30) (AAP 1996).

7 years.                     Stereoacuity at adult level.

10 years.                     End of critical period for monocular visual deprivation.

Table 1 Key:

→Required tests which may result in ophthalmology referral. An older child failing a test which results in referral at a younger age should also be referred.

[This table is from: Leffler CT. Visual impairment. In: Accardo PJ (ed). Developmental disabilities in infancy and childhood. Johns Hopkins Univ. Press. Balto., MD 2007. pp 501-520.]

Table 1 References:

American Academy of Pediatrics. Committee on Practice and Ambulatory Medicine. (1996) Vision Screening Guidelines. Pediatrics 98:156.

American Academy of Pediatrics; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2006 Feb;117(2):572-6.
(Erratum in: Pediatrics. 2006 Sep;118(3):1324.)

Edward D.P., Kaufman L.M. (2003) Anatomy, development and physiology of the visual system. Pedatr Clin N Am 50:1-23.

 
 

Table 2.  Disorders causing both ocular and neurological impairment.

 

  

 

 

 

                                                                                                                                  

Disorder.

Eye findings.

Other findings.

Etiology/

Inheritance.

ASSOCIATED WITH PIGMENTARY RETINOPATHY.

 

 

 

Alstrom syndrome.

Cone-rod retinal dystrophy.

SNHL, diabetes mellitus, obesity, dilated cardiomyopathy.

AR.  Chromosome 2p13. (Hearn 2002).

Bassen-Kornzweig syndrome (abetalipoproteinemia).

Retinitis pigmentosa.  Restrictive ocular motility.

Spinocerebellar ataxia. Acanthocytosis.  Celiac disease.  Diarrhea.

Abetalipoproteinemia. Mutation in microsomal triglyceride transfer protein gene.

Cockayne syndrome.

Pigmentary retinal degeneration. Cataracts. Optic atrophy.

MR, dwarfism, deafness, progeria, photosensitive rashes.

AR.  Chromosome 5 (Cockayne syndrome type A gene) or chromosome 10 (helicase).

Kearns-Sayre syndrome.

Progressive external ophthalmoplegia after age 5. “Salt and pepper” pigmentary retinopathy with normal arterioles. Rarely bone spicules.  Nyctalopia. Ptosis.  Onset under age 20, possibly in infancy.  Ptosis.

Heart block, SNHL, vestibular dysfunction, cerebellar ataxia, corticospinal dysfunction, muscular dystrophy, MR, spongiform CNS degeneration.  Short stature.  Diabetes mellitus.  SNHL.  Treat with coenzyme Q10.

Usually sporadic.  Mitochondrial DNA deletion.

Laurence-Moon-Bardet-Biedl syndrome.

Retinitis pigmentosa.

MR, polydactyly, obesity, hypogenitalism, paraplegia.

AR.  Multiple loci.

Neonatal adrenoleukodystrophy.

Cataract, optic atrophy, pigmentary retinopathy.

Psychomotor retardation.  MR. Seizures. Adrenal insufficiency.

AR.

Neuronal ceroid lipofuscinosis (Batten disease).

Pigmentary retinal degeneration.  Optic atrophy.  ERG extinction.

Cerebral atrophy. Ataxia.  Seizures. Dementia.

AR.  Multiple lysosomal gene mutations (Mole 1999).

Olivopontocerebellar atrophy (a spinocerebellar ataxia).

Pigmentary retinal degeneration. Nystagmus.  Slow saccades.  Optic atrophy.

Cerebellar and brainstem atrophy.  Dementia.  Dysphagia.  Dysarthria.

AD.  SCA-1 and SCA-2 genes on chromosomes 6 and 12, respectively.  (Koeppen 1998).

Refsum disease.

Retinitis pigmentosa. Optic atrophy.

Ataxia, polyneuropathy, Deafness, anosmia.  Distal extremity weakness. Cardiac arrhythmias.

AR.  Phytanic acid accumulation due to phytanoyl CoA hydroxylase deficiency. 

Usher syndrome.

Retinitis pigmentosa.

SNHL.  Type 1 (ataxia).  Type 2 (no ataxia, less severe SNHL).

AR.

Zellweger (hepatocerebrorenal) syndrome.

Infantile pigmentary retinal degeneration, nytagmus. Hypertelorism. Cataract. Microphthalmia.

Psychomotor retardation. Hypotonia. Seizures. Dysmorphic features. Renal cortical cysts. Hepatosplenomegaly.

Abnormality in peroxisomal enzymes on chromosomes 8, 1, or 7.  AR.

METABOLIC STORAGE DISEASES.

 

 

 

Fabry disease (Angiokeratoma corporis diffusum).

Cream-colored corneal verticillata. Posterior spokelike subcapsular, punctate, or wedge-shaped cataracts.  Conjunctival or retinal vascular abnormalities. Normal vision.

Cutaneous angiokeratomas, hypohydrosis, acral pain and paresthesias, renal cysts and failure.  Myocardial ischemia. Febrile crises.  Cerebral ischemia or hemorrhage.  Seizures. 

XR.  Alpha-galactosidase-A deficiency.  Xq22.  Accumulation of glycosphingolipids, including globotriaosylceramide.

Generalized gangliosidosis (GM1 gangliosidosis type I).

Foveal cherry red spot.  Optic atrophy. Corneal clouding.

Developmental delay/arrest. Neurologic deterioration. Hepatosplenomegaly. Skeletal dysplasia.

AR.  Beta-galactosidase deficiency.  Chromosome 3.  (Suzuki 1991).

Mucolipidosis type I (cherry red spot-myoclonus syndrome).

Foveal cherry red spot.  Optic atrophy.  Corneal opacities.  Lamellar cataracts.

Ataxia. Myoclonic epilepsy.  Hepatosplenomegaly.

AR.  Neuraminidase (sialidase) deficiency.  Chromosome 6.  (Bonten 2000).

Mucopolysaccharidosis I-H (Hurler syndrome) and I-S (Scheie syndrome)

Retinal pigmentary degeneration with spiculated appearance. Optic atrophy.  Progressive corneal opacity without edema.  ERG abnormalities.

MR, coarse facies, short stature. Joint stiffness.  Dysostosis multiplex. Rhinitis. Enlarged tongue.  Type I-S is less severe than type I-H.

AR.  Deficiency of lysosomal alpha-L-iduronidase with accumulation of dermatan sulfate and heparin sulfate.  Chromosome 4. (Scott 1990).

Mucopolysaccharidosis II (Hunter syndrome)

Retinal pigmentary degeneration with arteriolar narrowing. Optic atrophy.  Corneal clouding. ERG abnormalities.

MR, coarse facies, short stature.

XR.

Mucopolysaccharidosis III (Sanfilippo syndrome)

Retinal pigmentary degeneration with speculated appearance.  Optic atrophy. Corneal clouding. ERG abnormalities.

MR, coarse facies, short stature.

AR.

Niemann-Pick disease.

Foveal cherry red spot (primarily in type A).   Anterior capsular brownish opacification and posterior capsular cataract.

MR in infantile (type A).  Lung disease. Hepatosplenomegaly.  Short stature.  Pancytopenia.

AR.  Sphingomyelinase deficiency.  Chromosome 11p15.  Sphingomyelin accumulation in lysosomes of macrophages.

Sandhoff’s disease (GM2 gangliosidosis type II)

Foveal cherry red spot.

MR.  Muscle weakness.  Hepatosplenomegaly.

AR. Hexosaminidase A and B deficiency.  Chromosome 5.

Tay-Sachs disease (GM2 gangliosidosis type I).

Foveal cherry red spot.  Optic atrophy.  Abnormal visual evoked responses.

MR. Muscle weakness. Seizures.

AR.  Hexosaminidase A deficiency.  Chromosome 15.  (Kaback 2001).

PHAKOMATOSES.

 

 

 

Angiomatosis retinae (von Hippel-Lindau disease).

Retinal capillary hemangiomas with dilated feeder vessels and associated hemorrhage or exudates.

Cerebellar hemangioblastomas, renal cell carcinomas.  Cysts in pancreas, liver, epididymis, or ovaries. Pheochromocytoma.

AD.  Chromosome 3.

Ataxia-telangiectasia (Louis-Bar syndrome).

Oculomotor apraxia, bulbar conjunctival telangiectasias.

Mental retardation, progressive cerebellar ataxia in second year of life, skin telangiectasias, thymus hypoplasia, poor immune function, increased incidence of leukemia and lymphoma.

AR. Chromosome 11.

Encephalofacial angiomatosis (Sturge-Weber syndrome).

Choroidal hemangiomas.  Glaucoma ipsilateral to eyelid or conjunctiva hemangiomas.

Seizure, mental retardation.  CNS and meningeal hemangiomas. Facial hemangioma.  Nevus flammeus present at birth.

Sporadic occurrence.

Neurofibromatosis type 1 (von Recklinghausen’s disease).

Lisch nodules (iris hamartomas) in almost 100% of type 1 by age 21.  Relatives should be examined for Lisch nodules.  Optic nerve glioma, glaucoma, conjunctival neurofibromas, enlarged corneal nerves, pulsatile proptosis.

MR, learning disabilities, seizures, neurofibromas, axillary and inguinal freckling, sphenoid hypoplasia, glioma, pheochromocytoma.

AD.  Chromosome 17.

Neurofibromatosis type 2.

Posterior subcapsular cataracts. Optic nerve gliomas and meningiomas.

Vertigo, seizures, mental retardation, acoustic neuromas, hearing loss, CNS glioma, meningioma, pheochromocytoma.

AD. Chromosome 22.

Racemose angioma (Wyburn-Mason syndrome).

Retinal arteriovenous anastomoses.

Mental retardation.  Intracranial, especially midbrain, arteriovenous malformations with calcification.

Sporadic occurrence.

Tuberous sclerosis (Bourneville’s disease).

Retinal or optic nerve astrocytic hamartoma.

Seizures, mental retardation possible, CNS astrocytic hamartomas, achromic nevi (ash-leaf spots), café-au-lait spots, shagreen patches, visceral hamartomas in kidneys, bone, and heart.

AD.  Chromosome 9.

OTHER GENETIC CONDITIONS:

 

 

 

Aicardi syndrome.

Optic nerve hypoplasia.  Clear retinal lacunae.

Seizures.  Infantile spasms.  MR.  Lethal in boys.  Seen only in girls.  Absence of corpus callosum.  Gray matter abnormalities on MRI.

 

Albinism.

Foveal and optic nerve hypoplasia, nystagmus, reduced visual acuity, iris transillumination defects, refractive errors, strabismus, decreased proportion of uncrossed fibers at optic chiasm.

MR and immune defects (in Chediak-Higashi syndrome).

AR (Chediak-Higashi syndrome).  Tyrosinase-negative in complete oculocutaneous form.

Aniridia.

Iris hypoplasia or absence, nystagmus, anterior polar or disk-like cataracts, foveal hypoplasia, glaucoma

MR, Wilms tumor in sporadic patients.

2/3 AD,  1/3 sporadic chromosome 11 deletion.

Cornelia de Lange syndrome.

Common:  myopia, ptosis, nystagmus.  Also:  Optic atrophy, optic nerve colobomas, microcornea, astigmatism, microcornea, strabismus.

Prematurity.  Intrauterine growth retardation.  Low-pitched weak cry.  Initial hypertonicity.  MR.

Usually sporadic.  Rarely AD or AR.

Down’s syndrome.

Strabismus, nystagmus, keratoconus, total or punctate “snowflake” cataracts, myopia, astigmatism, glaucoma, ptosis, Brushfield spots (yellow iris spots). Epicanthal folds.  Eyelid laxity.

MR.  Large tongue.  Facial hypoplasia. Short and webbed neck. Short digits.  Palmar crease. Congenital heart disease.

Trisomy 21.

Friedreich’s ataxia.

Optic atrophy. Nystagmus.

Spinocerebellar degeneration. Ataxia. SNHL.

AR.  FRDA gene on chromosome 9, which encodes frataxin (Bradley 2000).

Galactosemia.

Oil droplet, lamellar, nuclear, or total cataract shortly after birth in 75%.

Lethargy, hypotonia, hepatomegaly, sepsis, poor growth, language deficits.  Treat with galactose restriction.

AR. Defect of galactose-1-phosphate uridyl transferase at chromosome 9p13.

Homocystinuria.

Myopia, lens subluxation, cataracts, glaucoma, pigmentary retinal degeneration.

MR, marfanoid appearance, thromboembolism, leg weakness.

AR.  Deficiency of cystathionine synthase with accumulation of homocysteine.  Chromosome 21q22.3 (Kraus 1994).

Joubert syndrome.

Congenital retinal dystrophy.  Oculomotor abnormalities.

Cerebellar hypoplasia, ataxia, MR, episodic hyperventilation.

AR.

Leber congenital amaurosis.

Poor vision.  Sluggish pupillary responses.  Large-amplitude nystagmus within first few months.  Eye pressing (ocular digital sign).  Retina normal initially, then with vessel attenuation, optic disc pallor, retinal pigment changes. Hyperopia.  Keratoconus. Abnormal or absent ERG.

MR, seizures. SNHL in 5%. 

AR rod-cone dystrophy.

Lowe (oculocerebrorenal) syndrome.

Cataracts, glaucoma.  Carriers have punctate cortical opacities.

Hypotonia, mental retardation, rickets, aminoaciduria.

AR or XR.  Decreased renal ammonia production.

Myotonic dystrophy (Steinert disease)

“Christmas tree” or posterior subcapsular cataract.

Swallowing and speech disability.  Muscle wasting.

AD.

Septooptic dysplasia (de Morsier syndrome).

Optic nerve hypoplasia.

Absence of septum pellucidum and agenesis or thinning of the corpus callosum. Pituitary abnormalities.  Encephalocele.  Brain MRI and endocrine evaluation warranted.

Usually sporadic.  Can be AR.  Hesx1 gene mutations (Bennett 2002).

CONGENITAL INFECTIONS AND TOXINS.

 

 

 

Cerebral palsy.

Strabismus, optic atrophy, nystagmus, refractive errors (Ashwal 2004).

Posture or movement disorder due to lesion of the developing brain.

Multiple etiologies: genetic, toxic, infectious, vascular insufficiency.

Congenital cytomegalovirus infection.

Chorioretinal inflammation, retinal hemorrhage.

MR.  Intrauterine growth retardation.  Hepatosplenomegaly. Petechiae. Cerebral atrophy.  Cerebal calcifications. SNHL.  1% of newborns.

Maternal infection with cytomegalovirus.

Fetal alcohol syndrome.

Small palpebral fissures (blepharophimosis), ptosis, telecanthus, anterior segment dysgenesis, strabismus, corneal opacities, optic nerve hypoplasia, retinal vascular tortuosity.

Cognitive impairment.  Congenital heart disease.  Facial abnormalities with absence of a philtrum and a broad upper lip.

Maternal ethanol ingestion.

Herpes simplex, intrauterine.

Chorioretinitis, microphthalmia.

Encephalitis.

Intrauterine disease less likely than transplacental acquisition.

Rubella, congenital.

“Salt and pepper” retinopathy, nuclear or total cataract, glaucoma, microphthalmos.

Cardiac defects, deafness.

Maternal infection during first trimester.

Syphilis, congenital.

Choroiditis.

Hepatosplenomegaly. Pneumonia.  Rhinitis. Neurosyphilis. Skin lesions.

Transplacental passage of Treponema pallidum.

Toxoplasmosis, congenital.

Retinochoroiditis, focal atrophic and pigmented scars.  Focal vitritis.

Cerebral calcifications. Convulsions. Fever. Hydrocephalus. Microcephaly.

Maternal infection with toxoplasma gondii.

AR = autosomal recessive.  MR=mental retardation.  SNHL=sensorineural hearing loss.  XR=X-linked recessive.  XD=X-linked dominant.

 

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