Rudolph's Pediatrics, 22nd Ed.

CHAPTER 585. Amblyopia

Anthony G. Quinn and Alex V. Levin

Amblyopia is a monocular (or occasionally binocular) reduction of vision due to impaired visual development by the brain. It is sometimes referred to as lazy eye, although this lay term may also be applied to describe strabismus (ie, a wandering eye). In addition to the subnormal visual acuity, sophisticated testing will also reveal possible deficiency of motion sensitivity, contrast sensitivity, color sensitivity, visual field, and stereoacuity. The functional and anatomical changes in the visual brain result from disruption of normal visual experience during development. The severity and reversibility of amblyopia relate closely to the cause of the visual disturbance and the child’s age.

Normal visual development requires that both eyes are in good focus, with normal ocular structures and cerebral visual pathways. In addition, both eyes need to be look at the same thing at the same time. The three main types of amblyopia are

1. Deprivational—caused by physical obstructions to vision such as congenital cataract, corneal opacification, eyelid capillary hemangioma, or ptosis occluding the visual axis;

2. Strabismic—caused by misalignment of the visual direction of the two eyes; and

3. Ametropic—caused by asymmetric monocular or, occasionally, binocular refractive error (glasses prescription).

In deprivational amblyopia, the physical abnormality of the eye or lid itself may cause the vision to be reduced. Amblyopia is visual loss in addition to the loss caused by the physical obstruction. For example, if an opacity in the lens (cataract) blurs the vision to 20/60, the brain will prefer the other normal eye and will “ignore” the eye with cataract. Amblyopia will then further impair the visual development in the eye with cataract, causing the vision to be even worse than the 20/60 the eye would have been capable of if it were not for the superimposed amblyopia.

The most common form of ametropic amblyopia is anisometropic amblyopia, caused by the two eyes having a different focus, such that one eye is out of focus when the other is in focus. The defocus can be caused by a difference in the refractive power of the two eyes. For example, if one eye does not need glasses and the other is very nearsighted, the myopic eye may develop amblyopia in addition to the blurring caused by myopia. If both eyes are farsighted—a very common finding in young children that does not require glasses, because they can focus using their own intrinsic eye muscles (accommodation)—but one eye is more farsighted than the other, the brain will prefer to view through the eye with less farsightedness. As a result, when the eye with less farsightedness is focused, the other eye is still not completely focused. The brain will prefer the better-focusing eye, and the remaining eye will become amblyopic.

Typically, deprivational amblyopia is more severe than strabismic amblyopia, which is usually more severe than amblyopia due to refractive error. Mixed strabismic and anisome-tropic amblyopia is usually more severe than strabismic amblyopia alone.

There is a fundamental difference between strabismic amblyopia and the other two forms. Deprivational and ametropic amblyopia result from a lack of a well-focused, formed image on the retina, which leads to reduced vision. In strabismic amblyopia, the retinal images are initially in good focus, but due to the misalignment of the visual axes of the eyes, the brain suppresses the image from one eye (preventing diplopia), resulting in reduced vision from that eye.

The two eyes are “in competition” for cerebral neuronal connections; if the image from one is suppressed or out of focus, that eye loses the competition. This period of competition occurs in what is known as the “critical period” of visual development, after which the visual brain loses plasticity.

Monocular amblyopia causes little if any reduction in the child’s quality of life. But if there is loss of vision in the better (nonamblyopic) eye—for example, due to trauma or other coincidental ocular disease—then a major visual disability may result, as both eyes will have subnormal vision, if not legal blindness. It follows that treating amblyopia is likely to be very cost-effective, because the effect of improving vision is felt over the child’s whole life and offers protection should the other eye suffer visual disease.1

Binocular amblyopia is much less common than monocular amblyopia. It usually occurs in children who have bilateral high-refractive errors that are not treated with glasses at an early age. This underscores the importance of vision screening by pediatricians at well-child examinations, as a child with uncorrected refractive error might very well appear functionally normal because the visual demands of young childhood do not present a sufficient enough challenge to elicit symptoms. Yet, the child’s brain is not receiving a clear enough image to allow for proper visual development. Later, when the deficit is discovered, it may be too late for glasses to fully correct the problem. If they receive early intervention, some children will show a slow but steady improvement in visual function and typically achieve normal visual acuity within 1 year of being prescribed corrective spectacles.2

EPIDEMIOLOGY

Amblyopia affects 2% of the population and is the leading cause of monocular reduced vision in childhood in the world’s wealthier economies.3 It is more common in children with a family history of conditions such as strabismus, refractive error, and congenital cataract. It is also more common in children with systemic abnormalities such as Down syndrome and premature birth, due to the increased frequencies of strabismus and refractive error associated with these conditions. Bilateral amblyopia has been shown to have a prevalence of 0.5% in one study from Germany.4 Robaei and coworkers reported that the cause of monocular amblyopia is anisometropia in 34.4%, strabismus in 37.5%, and mixed in 18.8%.3 There is an increased risk of losing the better eye, in particular due to trauma, in patients with unilateral amblyopia,5,6 and the lifetime risk of vision loss in the better eye is at least 1.2%.7

PATHOPHYSIOLOGY

The pathophysiology of amblyopia was, in part, the subject of the Nobel Prize–winning research by Hubel and Wiesel.8 They studied the primary visual (striate) cortex in 4- to 6-week-old kittens when the eyelid of one eye was sutured closed for 3 days or more, from birth. They looked at the size of ocular dominance columns (areas in the striate cortex that carry neuronal input from either the left or the right eye) via the lateral geniculate nucleus in the thalamus. The surgically closed eye had much attenuated ocular dominance columns in the striate cortex, and the open eye had larger-than-normal columns. This experimental situation is analogous to that of human infants with a dense monocular cataract. In this instance, good visual results necessitate surgery by 6 weeks of age. After 6 weeks of age, there is a steady and rapid reduction in the chances for the best possible corrected visual acuity due to irreversible organic brain changes in the vision pathways.9

In contrast, critical periods for strabismus and anisometropia in humans are longer but not well defined experimentally. Ocular dominance columns in the striate cortex are not anatomically altered in human strabismic or anisometropic amblyopia.10,11 Functional magnetic resonance imaging (MRI) studies of brain activity in strabismic and anisometropic amblyopes show that amblyopic eyes have a reduced share of cortical territory than normal eyes. However, many important questions remain to be resolved in this area, particularly the relative impact of amblyopia on the striate versus extrastriate visual processing areas.12

DIAGNOSIS

In unilateral amblyopia, the amblyopic eye typically has visual acuity of two or more lines worse than the nonamblyopic eye. This finding is a criterion for referral for an ophthalmology assessment. Visual loss in amblyopia ranges from mild to severe, with about 25% of children having visual acuity in the amblyopic eye of worse than 20/100 and about 75% having 20/100 or better.13-16 Amblyopia is detected by measuring visual acuity. Standard visual acuity testing using charts creates a “crowded” stimulus, which accentuates the vision deficit and makes it more likely to be detected. If single letters/figures/numbers are used, the stimulus is no longer crowded and performance will be enhanced. Therefore, pediatricians may miss amblyopia if they use such isolated stimuli. In children who are too young to perform literate or picture tests, the pediatrician must look for an unequal preference of fixation. If such a preference is found, then referral to an ophthalmologist is indicated to ascertain the cause.

TREATMENT

Treatments of unilateral amblyopia consist of optimizing the clarity of the visual axis and occlusion of the visual axis of the unaffected eye to give the brain the opportunity to focus on developing vision in the amblyopic eye. In ametropic amblyopia (unilateral or bilateral), spectacle correction alone may be sufficient. If there is an organic cause of the amblyopia (eg, ptosis, cataract), the abnormality may first need to be corrected (eg, lid surgery, cataract removal) before amblyopia treatment can proceed. To the contrary, in strabismic amblyopia, the amblyopia is usually treated first, followed by eye muscle surgery to straighten the eyes; the surgical result will be enhanced if the patient has equal vision in both eyes, thus allowing the brain to have a greater chance of keeping the eyes aligned.

Patching (occlusion) of the sound eye is the mainstay of amblyopia treatment. The patch goes over the periorbital skin of the good eye. If the child is wearing glasses, the patch is best to go on the skin and not on the glasses (Fig. 585-1), even though options for occluding one spectacle lens are available. In selected cases, in particular for those with a farsighted good eye or mild to moderate amblyopia, optical penalization of the sound eye, typically with atropine eye drops, may also be effective. The drops blur the good eye to a point where the brain now prefers the amblyopic eye. Children are encouraged to engage in visually stimulating near activities during the treatment period to increase the use of the amblyopic eye.

In the last decade, there has been a leap forward in our evidence base for amblyopia treatment, with the advent of multicenter, prospective, randomized clinical trials. The studies have revealed many important findings. Children with monocular ametropic amblyopia, treated with spectacles to correct their refractive error and with patching to correct their amblyopia, have better visual acuity than those treated with spectacles alone or those who are not treated. Improvement for children with initial visual acuities in the range of 20/60 to 20/100 tend to be better with treatment than in those who start with less severe amblyopia.17 The results of this study must not be extrapolated to strabismic or deprivational amblyopia. As the mildest form of amblyopia, anisometropic amblyopia is the easiest form to treat, and even teenagers can respond to treatment.

The Pediatric Eye Disease Investigator Group (PEDIG) has published extensively on amblyopia in recent years. They have shown that in the treatment of moderate amblyopia (20/40 to 20/100), patching the sound eye for 6 hours or more a day is as effective as using atropine eye drops (one drop per day, used with sunglasses and a hat in sunlight as needed).18 Atropine and patching treatments were both well tolerated and accepted by the child and the family, but overall, atropine received more favorable scores on evaluation by the families.19 PEDIG compared patching of 2 hours versus 6 hours per day in children under 7 years old with vision of 20/40 to 20/80 caused by strabismus, refractive error, or both. They found no significant difference in outcome, although the improvement with more daily hours of patching was faster. Both groups had their patching combined with 1 hour of near visual activities each day.20 PEDIG also reported that full-time patching of the sound eye was as effective as patching for 6 hours a day, in patients aged 3 to 6 years with severe (20/100 to 20/400) unilateral amblyopia. Both groups had improvement in visual acuity in the amblyopic eye of slightly less than five lines of the visual acuity chart.

PEDIG also examined the effectiveness of treating amblyopia in older children, ages 7 to 17 years, with baseline visual acuity of 20/40 to 20/400 and found that up to 53% of those ages 7 to 12 years and 47% of those ages 13 to 17 years could still improve. This study tells us that it is well worth attempting treatment in older children suffering from amblyopia, although compliance may be a challenge. In the past, there had been little confidence in attempting treatment after 7 to 8 years of age.21 Another question that PEDIG studied was how stable visual acuity improvements are following treatment of amblyopia. They studied 80 patients age 7 to 12 years whose visual acuity had improved two or more lines in the amblyopic eye after treatment with patching or atropine but who had ceased treatment, apart from spectacle wear, for 1 year. Visual acuity in the large majority was stable.22

COMPLICATIONS OF AMBLYOPIA TREATMENT

Amblyopia treatment is very safe, provided it is well supervised. It is possible to produce “occlusion amblyopia” (sometimes referred to as reverse amblyopia), in which the sound eye becomes amblyopic, especially if treatment of the sound eye is not stopped or tapered when the originally amblyopic eye achieves visual acuity equal to the sound eye. This can be avoided by careful follow-up of treated children. Now that they have been shown to be equivalent in efficacy to more intensive regimes, less intensive patching regimes for moderate amblyopia are much less likely to produce this complication than, for example, full-time occlusion of the sound eye. Occlusion amblyopia is particularly uncommon in deprivational amblyopia. For example, children with unilateral congenital cataracts may undergo years of nearly full-time patching without apparent harm to the eye without cataract. But careful follow-up is well advised.

Figure 585-1. Note that the patch is on the skin and not on the glasses. The patch is on the child’s healthy, nonamblyopic right eye. Amblyopia is present in the other eye.

Intractable diplopia is an extremely rare possibility when patching children older than age 7 years. The risk is probably in the order of 1:10,000 or less.

More innocuous complications include contact dermatitis of the periorbital skin due to the patch (Fig. 585-2). This may often be handled by a short course without the patch with or without topical steroids. Switching the brand of patch may then be helpful. If the child is developing abrasions of the periocular skin from removing the patch, parents may place a permanent piece of micropore paper over the affected area and continue patching, with the patch going on and coming off the tape rather than the skin. The micropore tape will spontaneously fall off when the skin underneath is healed. Systemic reaction to atropine eyedrops may occur. In such cases, and in children under 1 year old, we recommend atropine 0.5% instead of the more typical 1% solution.

Perhaps the most common problem with patching is noncompliance. Understandably, children will react adversely when asked to view the world with their blurry eye. Infants may fall asleep when the patch is applied, and older children will go to extraordinary lengths to either pull the patch off or resist in other ways. Children may be given the choice of the sting of the atropine or the occlusion of the patch. Other “tricks” are available such as preparations to increase patch adhesiveness, occlusive dressings over the patch, mitts over the hands, or arm restraints. Perhaps most importantly, parents need to use positive reinforcement techniques and have the support of their physicians and similarly affected families. Much information on patching can be found at the website of the Pediatric Glaucoma and Cataract Family Association (PGCFA). It has often been recognized by pediatric ophthalmologists and parents that amblyopia is one of the most difficult eye disorders of childhood to treat because of the compliance issues.