Amblyopia is a disorder of the development of sight. It is due to the failure of cortical visual development in one or both eyes from ocular pathology early in life. Often, amblyopia is referred to as a "lazy eye" by the general public. Amblyopia results in permanent decreased vision in the pathological eye if not treated early enough, even if the ocular pathology is removed later on in life. It is the most common cause of decreased vision in a single eye among children and younger adults.
Amblyopia occurs early in life when the developing visual system fails to transmit a sharp image to the visual cortex. Amblyopia can be the result of media opacities, cataracts, strabismus, or anisometropic refractive errors that place one eye at a developmental disadvantage to the other. Amblyopia usually occurs unilaterally but can occur bilaterally with cataracts of both eyes or high refractive errors. Our visual experience as infants and children determines how we see as adults.
Amblyopia is diagnosed by identifying diminished visual acuity in one or both eyes that are out of proportion to the structural abnormality of the eye, excluding any other visual disorders as the underlying cause. It can be defined as an interocular difference of two lines or more in acuity when the refractive error is corrected. In young children, visual acuity can be difficult to measure but can be estimated by observing the reactions of the child when one eye is covered, including watching the child's ability to follow objects with one eye.
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Amblyopia can be broken down into three main causes: deprivation, strabismus, and refractive. Deprivation amblyopia comes from any pathology that inhibits the visual pathway. This could be a cataract, corneal opacity, damage to the retina, or optic nerve pathology. It can even be caused by the absence of visual stimuli, such as covering one eye or living in complete darkness. Deprivation causes the most severe form of amblyopia. Strabismus is when both eyes do not align. The pediatric brain prevents diplopia by suppressing the visual input in one eye, leading to impaired visual development in that eye. The strabismus can be treated with surgery or prism glasses; however, amblyopia often persists despite treating the underlying strabismus. Refractive amblyopia stems from blurred visual input from hyperopia, astigmatism, or myopia. Generally, an eye with hyperopia or astigmatism has a higher likelihood of developing amblyopia than myopia, as a myopic eye will still have near objects in focus.
Typically the more profound the visual deprivation, the more severe the resultant amblyopia will be. The critical period for visual development is roughly the first seven years of life, with the first few years and even months being the most critical. The later the amblyopia treatment begins, the more difficult it becomes to reverse clinically. This is because early-onset visual deprivation results in permanent anatomic changes in the magnocellular (M) and parvocellular (P) visual pathways. For this reason, surgeons may need to operate on dense congenital monocular cataracts very early, often within a week after discovery. Even a few months with a congenital cataract could lead to irreversible amblyopia. With binocular, equally dense congenital cataracts, there is a little more flexibility, usually a few weeks.
In its various forms, amblyopia has historically been cited to affect up to 3% of the population, with a 1.2% lifetime risk of vision loss from this condition. More recently, the global prevalence of amblyopia has been cited to be around 1.75%. Anisometropia was the most common cause of amblyopia, followed by mixed anisometropia and strabismus, strabismus, and visual deprivation. The diagnosis for mixed and strabismic amblyopia is typically made at an earlier age (7.4) than anisometropic amblyopia (12.7). The prevalence of amblyopia appears to be equal between right and left eyes. No sex predilection has been found.
With monocular visual deprivation during visual development, there is competition between the neural networks of the two eyes for impact on cortical neurons. Different aspects of neuronal selectivity, such as synaptic plasticity, activity-dependence, and neuronal network learning, have different sensitive periods and are therefore affected differently by the types of vision deprivation involved.
It is the anatomic relationships of photoreceptors to ganglion cell receptor fields, ganglion cell receptor fields to the layers in the lateral geniculate, and the lateral geniculate to the layers of the visual cortex that determine amblyopia. The age of onset and duration of the disability determines its depth. The earlier the onset and the longer it goes untreated, the harder amblyopia is to correct.
History and Physical
A thorough medical history of the patient should be queried all the way back to childhood. Medical records should be obtained if it is still possible to get them. Important questions to ask include when did decreased vision in the suspected eye start and does the patient has any history of refractive correction, ocular trauma, ocular pathology, amblyopia treatment, and ocular surgeries. Sometimes the patient may be unaware of this history, so getting the history from the parents on family members may be of help.
Any patient with suspected amblyopia should have a complete eye exam. The visual acuity of each eye should be checked individually with the patient’s refractive correction. Visual acuity may be overestimated in amblyopic eyes when using individual visual targets, so it may be beneficial to bracket the visual targets for accuracy. Steroacuity testing should be performed, as amblyopic eyes often have impaired or absent stereopsis. All patients with decreased vision should have refraction done. In children, this often should be done after cycloplegia to get cycloplegic refraction and uncover underlying hyperopia. The pupillary reflex should be tested with light, and the eye in question should be assessed closely for a relative afferent pupillary defect using the swinging flashlight test. The intraocular pressure (IOP) should be checked in all patients that are able to undergo the testing. Sometimes this testing is deferred in patients that have difficulty undergoing the testing, especially children. Extraocular motility and confrontational visual fields should be assessed in all patients that are able to do this testing. Tropias and phorias should be assessed with the cover-uncover test and alternate cover test. This can uncover any underlying strabismus, a common cause for amblyopia. All patients with suspected amblyopia should undergo a dilated exam. When examining the eyes, special attention should be paid to the ocular structures involved in vision: the cornea, lens, retina, and optic nerve.
Further testing that should be considered when evaluating for amblyopia includes formal visual field testing, optical coherence tomography (OCT), fundus photography, and an electroretinogram (ERG). Brain and orbit imaging can be considered if there is suspicion for a compressive lesion along the visual pathway. Amblyopia is a clinical diagnosis, and additional patient testing should only be done to evaluate for other ocular pathology causing decreased vision. Brain magnetic resonance imaging (MRI) in research has shown decreased visual cortex size in patients with amblyopia. However, MRI is not recommended as a diagnostic test for amblyopia.
Treatment / Management
The initial treatment of amblyopia depends on the underlying cause. Deprivation amblyopia should first be treated by removing the obstructive pathology. This may be cataract surgery, retinal detachment repair, corneal surgery, or treatment for a variety of other ocular pathologies. Refractive amblyopia often is the most amenable to treatment. Treatment of the patient’s entire refractive error with corrective lenses may be treatment enough to reverse the amblyopia. In strabismic amblyopia, strabismus repair may realign the eyes; however, this rarely is enough to reverse amblyopia completely.
All forms of amblyopia often need to utilize visual penalization of the non-amblyopic eye to force visual development in the amblyopic eye. The most common form of visual penalization is patching the non-amblyopic eye. The amount of time the non-amblyopic eye is patched per day varies with the severity of the amblyopia. Practitioners often patch for two hours, six hours, or sometimes even full-time. Visual activity such as reading, watching television or playing video games while patching may be helpful, as the patient will be forced to use the amblyopic eye and may be more cooperative with the patching if it is associated with an enjoyable activity. Patching of the non-amblyopic eye as a treatment for amblyopia began in the 16th century. It remains the mainstay of therapy to this day. If the patient cannot reliably go through patching therapy, pharmacologic amblyopia treatment is an option. A cycloplegic drug (usually atropine) can be used to inhibit accommodation in the non-amblyopic eye. The benefit of this therapy includes ease of putting in one drop daily compared to having to maintain a patch over the eye for hours at a time. This therapy has been found to have similar effectiveness to patching in the correct patients. However, patients who are myopic or emmetropic in the non-amblyopic eye may not benefit from pharmacologic therapy since these eyes will maintain the focus of objects at certain distances.
The older the patient gets, the more likely the plasticity of the brain to reverse amblyopia is no longer present. The exact age at which amblyopia treatment becomes futile is not uniformly agreed upon. However, The Pediatric Eye Disease Investigator Group found that patients from seven to twelve showed at least some benefit from amblyopia treatment, compared to patients thirteen and older, who showed minimal improvement with treatment.
Amblyopia is a diagnosis of exclusion, meaning that amblyopia can only be diagnosed when all other ocular or cerebral pathology has been ruled out as the cause for decreased visual acuity. Common causes of decreased visual acuity include refractive error, cataract, corneal pathology, retinal pathology, and optic nerve pathology. Most of these pathologies can be ruled out by a complete eye exam. Cerebral visual impairment and functional (non-organic) vision loss should also be considered.
The prognosis of amblyopia is dependent if it is treated at an early age and the severity of amblyopia. Amblyopia has significant morbidity and is a common cause of monocular decreased vision. At least 75% of children treated with occlusion therapy do show a good return of vision. However, in at least 50% of children, there is a slight decrease in visual acuity over time. The best outcomes are in children who are referred early in life. However, in many cases, the actual real-life images may be slightly altered in many children as they grow. However, if treated, more than 70% of patients have significant vision improvement within 12 months. Even after treatment, there may be some decline in vision over the coming years. Risk factors for failure to restore vision include age at which treatment for the condition started (later treatment tends to have a worse outcome), deprivation amblyopia, and poor initial visual acuity.
The main complication of amblyopia is an irreversible, lifelong decrease in vision. These visual functional abnormalities include reductions in visual acuity, contrast sensitivity, vernier acuity, spatial distortion, abnormal spatial interactions, and impaired contour detection. Patients with amblyopia will have binocular abnormalities such as impaired stereoscopic acuity and abnormal binocular summation. The monocular vision deficits are usually specific to only the amblyopic eye. However, subclinical deficits of the non-amblyopic eye have also been demonstrated.
People with amblyopia have difficulty seeing three-dimensional images hidden in stereoscopic displays such as autostereograms. Perception of depth, however, from monocular cues such as size, perspective, and motion parallax in the non-amblyopic eye typically remains normal.
Learning may also be impaired in children with amblyopia. Children with amblyopia read and answer multiple-choice questions slower than children that do not have amblyopia. Another possible complication of amblyopia includes worsening strabismus due to impaired binocular fusion.
Deterrence and Patient Education
Parents should be educated on the importance of early vision exams for their children. School vision screenings may be the first time amblyopia is suspected. If a child has been diagnosed with amblyopia, parents should be educated that if untreated, the vision loss from amblyopia is typically irreversible. The importance of treatment should be emphasized with the parents. Children may not want to wear glasses or patches, but parents need to ensure that their child goes through with the treatment. Providers should encourage parents at every visit to continue treatment, as amblyopia treatment may need to continue for a long period of time.
Pearls and Other Issues
Amblyopia or lazy eye is a disorder of sight due to the eye and brain not working together. It results in decreased vision in an eye that may appear normal. It is the most common cause of decreased vision in a single eye among children and younger adults. In practice, the earlier the onset of its sensitive period, the more profound the visual deprivation and the deeper the resultant amblyopia. Refractive amblyopia is typically the most amenable to treatment, especially astigmatic amblyopia. Sometimes refractive correction alone may be all that is needed for treatment. If the amblyopia does not resolve, then patching the non-amblyopic eye is indicated.
Enhancing Healthcare Team Outcomes
Pediatric ophthalmologists are typically the physicians who treat amblyopia, although optometrists also have experience in treatment. It is critically important that the patients are referred to a provider that has training in amblyopia treatment because mismanagement of this condition can lead to irreversible vision loss. The first provider to suspect amblyopia often will not be an ophthalmologist or optometrist. It may be a pediatrician, family doctor, nurse, or medical assistant. Family members spend more time with the patients and may be the first to notice preferential fixation of the non-amblyopic eye. Many cases of amblyopia will be caught during vision screenings. These screening programs are critical to catching amblyopia early. [Level 5] Without an appropriate referral, the child is at risk for permanent vision loss. The longer the condition remains undiagnosed and untreated, the poorer the outcome. Health care providers need to communicate effectively with other providers as well as parents to prevent irreversible vision loss from this condition.
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