Anisometropic amblyopia is the second most common cause of amblyopia. Anisometropic amblyopia occurs when unequal focus between the two eyes causes chronic blur on one retina. Anisometropic amblyopia can occur with relatively small amounts of asymmetric hyperopia or astigmatism. Generally, larger amounts of anisomyopia are necessary for amblyopia to develop.
Anisometropic amblyopia is an insidious disease because unlike strabismic amblyopia, the eyes appear normal to an observer. Anisometropic amblyopia is most commonly caught by vision screening either in a pediatrician’s office or in the school system.
The prevalence of amblyopia is reported as 2-4% in North America and is the primary cause of unilateral vision loss in children. According to Hess et al., one third of amblyopia cases are caused by anisometropia, one third by strabismus and one third from a combination of the two. However, other authors have reported that 50% of cases with amblyopia are caused by anisometropia.
As previously discussed, anisometropic amblyopia can occur when there is a difference in refractive error between the two eyes.
It is generally accepted that pathological changes from amblyopia occur primarily in the primary visual cortex and lateral geniculate nucleus. Experiments by Hubel and Wiesel were the first to demonstrate neuronal loss in the primary cortex (V1) using experimental deprivation amblyopia in kittens. Subsequent amblyopia studies in animals have shown neurological changes in layer IVc of V1 and the lateral geniculate nucleus.
Recent studies using PET, FMRI and VEP have verified that there is significant loss of neural activity in the visual cortex. However, the ocular dominance columns do not appear to shrink in size in patients with strabismic or anisometropic amblyopia
Although amblyopia is most commonly detected by a difference in optotype visual acuity, studies have shown that changes occur in different areas of the visual system. Deficits from amblyopia affect neuronal receptive fields, contrast sensitivity, and grating acuity. These areas of the visual system may be affected differently depending on the type of amblyopia (deprivation, strabismus, anisometropia).
It is well known that patients with amblyopia show better visual acuity with isolated or single letter visual acuity than linear acuity. This is recognized as the crowding phenomenon and is speculated to be caused by contour interaction. Studies using spatial summation have shown that neuronal receptive fields are larger in the amblyopic visual system. This may explain why patients with amblyopia have difficulty resolving surrounding characters of similar size when testing their amblyopic eye.
Many studies have shown that contrast sensitivity is decreased in patients with amblyopia. The decrease in contrast sensitivity for patients with anisometropic amblyopia is more pronounced at mid and high spatial frequencies. In 1980 Hess et al. demonstrated that patients with anisometropia amblyopia have decreased contrast sensitivity across the entire visual field (central and peripheral field). Conversely, contrast sensitivity was only decreased in the central visual field in patients with strabismic amblyopia. A recent study by Levi et al. found that contrast sensitivity was reduced in anisometropic amblyopia, however these contrast deficits were not apparent in bilateral refractive amblyopia.
Grating acuity and Vernier acuity have been shown to be equally decreased in patients with anisometropic amblopia. However, patients with amblyopia secondary to strabismus show a greater loss of Vernier acuity than grating acuity. Patients with anisometropic amblyopia do not show any visual field asymmetry when testing vertical grating resolution. Conversely, vertical grating resolution is asymmetric in patients with strabismic amblyopia and is dependent on their type of eye-misalignment.
Treatment of anisometropic amblyopia starts with eliminating the competitive advantage of the dominant eye. This is usually done by prescribing the cyclopegic refraction to the child for full time wear. Sometimes children will not tolerate their full hyperopic correction and so symmetric decreases in plus lens power may be required. Some children will respond to refractive correction alone.
For those with residual amblyopia after refractive correction, the next step is optical penalizations for the dominant eye. There are a number of techniques for optical penalization including occlusion (both part time and full time), placement of filters, refractive defocus, and pharmacologic blurring. The positives and negatives of different penalization techniques are discussed below.
Studies have shown that some patients with anisometropic amblyopia may show improvement in visual acuity while wearing their glasses full-time, without concurrent patching. A retrospective study by Steele et al. showed that one third of the patients with pure anisometropic amblyopia resolved without the need of occlusion therapy. The length of recovery time was directly proportional to the severity of amblyopia. The mean time to resolution was 5.8 months. In 2006 a prospective study by PEDIG reported that 27% of children with anisometropic amblyopia aged 3 to 6 resolved with spectacles alone. Visual acuity continued to improve in 48% of patients beyond 5 weeks.
A child maintains a high level of cortical synaptic plasticity until they reach visual maturity (approximately 7 to 9 years of age). During these early years, amblyopic neural deficits and vision loss can be reversed by occluding the non-amblyopic eye. Visual plasticity is inversely related to a child’s age, thus patching is more effective at an early age. However, there are studies that have shown that occlusion therapy can be effective in adolescent children .
A more detailed review on treatment efficacy and recommended patching dosage can be found in the EyeWiki article titled Amblyopia. The amblyopia studies performed by PEDIG are also reviewed in this section.
Atropine is an anticholineric drug that works as a competitive inhibitor for the muscarinic acetylcholine receptor. Optical penalization is also used to treat amblyopia by using atropine 1% to paralyze accommodation and induce blur in the non-amblyopic eye. If a patient has a hyperopic refractive error in their dominant eye then reducing this lens to plano will enhance the affect of pharmacologic penalization. Please see the Eyewiki article titled Amblyopia for more information on atropine treatment.
Neutral Density Filter
A recent study by PEDIG analyzed the efficacy of Bangerter filters for the treatment of moderate amblyopia as compared to part-time patching. The authors found that after 24 weeks of treatment, the mean visual acuity improvement in the patching group was only half a line better than the Bangerter filter group. The study also included a questionnaire to asses the negative impact of each treatment modality. They found that the Bangerter filter was a less disruptive treatment option for both the child and family. The authors concluded that the Bangerter filter is effective for treating moderate amblyopia and may be a useful alternative for patients with poor patching compliance. It is important to mention that patients with minimal refractive error in their non-amblyopic eye will likely look over their glasses. These patients will likely not respond as well to Bangerter filter treatment.
A more recent treatment option is the use of pharmacologic neurotransmitters for patients that are non-responsive to standard amblyopia treatment. The neurotransmitters are believed to enhance cortical plasticity. Dopamine is a neurotransmitter that is active in the retina and the cortex but does not cross the blood brain barrier. A precursor molecule known as levodopa does cross the blood brain barrier and is converted to dopamine in the brain. Levodopa is currently used to treat patients with Parkinson disease and children with dystonia. Numerous studies have reported that patients who receive levodopa-carbidopa with patching show more improvement than patients who receive a placebo and patching. However, there are conflicting results in the literature on the stability of visual acuity after cessation of treatment. In 2002 Leguire et al. analyzed the regression rates of three previous levodapa studies. They found that after the cessation of treatment, the regression rates of levodopa and patching treatment were similar to the regression rates of patching therapy alone.
PEDIG is currently conducting a multi-center, double-masked randomized study on levodopa-carbidopa for the treatment of amblyopia. This study will provide a better understanding of the efficacy and long-term stability of levodopa treatment for amblyopia.
The prognosis for treatment varies significantly based on the age of the child and the type of treatment initiated. In general, treatment is more successful if the child is treated at a younger age. Although refractive amblyopia is more commonly associated with anisometropic hyperopia, unilateral high myopia tends to have a worse prognosis.
- AAPOS Information on Amblyopia
- Visit EyeSmart from the American Academy of Ophthalmology for a patient-friendly summary of Amblyopia.
- American Academy of Ophthalmology. Pediatric Ophthalmology/Strabismus: Anisometropic amblyopia Practicing Ophthalmologists Learning System, 2017 - 2019 San Francisco: American Academy of Ophthalmology, 2017.
- American Academy of Ophthalmology. Basic and clinical science course. Pediatric Ophthalmology and Strabismus. Section 6. San Francisco: American Academy of Ophthalmology, 2006.
- Hess RF, Field DJ, Watt RJ: The Puzzle of Amblyopia. Vision: Coding and Efficiency. Cambridge University Press 1990; 267-280.
- Flynn JT. 17th annual Frank Costenbader Lecture Amblyopia revisited. Pediatr Ophthalmol Strabismus 1991;28(4):183-201.
- Wiesel TN, Hubel DH. Single-cell responses in the striate of kittens deprived of vision in one eye. J Neurophysiol 1963;26:1003-1017.
- Barrett BT, Bradley A, McGraw PV. Understanding the neural basis of amblyopia. Neuroscientist 2004;10:106-117.
- Campos, E. Amblyopia; Major Review. Survey of Ophthalmology 1995;40(1):23-39.
- Bradley A, Freeman RD. Contrast Sensitivity in anisometropic amblyopia. Invest Ophthalmol Vis Sci 1981;21:467-476.
- Levi, D.M, McKee, S.P, Movshon, J.A. Visual deficits in Anisometropia. Vision Research 2011;51:48-57.
- Steel AL, Bradfield YS, Kushner BJ et al. Successful treatment of anisometropic amblyopia with spectacles alone. J AAPOS 2006;10(1):37-43.
- Pediatric Eye Disease Investigator Group: Treatment of anisometropic amblyopia in children with refractive correction. Ophthalmology 2006;113:895-903.
- (ATS3) Pediatric Eye Disease Investigator Group. Randomized trial of treatment of amblyopia in children aged 7 to 17 years. Arch Ophthalmol. 2005;123(4):437-447.
- (ATS 9) Pediatric Eye Disease Investigator Group. Patching vs atropine to treat amblyopia in children aged 7 to 12 years: a randomized trial. Arch Ophthalmol 2008; 12:1634-42.
- Pediatric Eye Disease Investigator Group. A randomized trial comparing Bangerter filters and patching for the treatment of moderate amblyopia in children. Ophthalmology 2010;17(5):998-1004.
- Leguire LE, Komaromy KL, Nairus TM, Rogers GL. Long-term follow-up L-dopa treatment in children with amblyopia. J Pediatr Ophthalmol Strabismus 2002;39:326-330.