We Have Fixed Hundreds Of Lazy Eyes

Amblyopia is clinically defined as reduction of best-corrected visual acuity (BCVA) that is not solely ascribed to a structural abnormality or refractive error in the eye, rather is caused by abnormal binocular interaction during the critical period of neurosensory development [1]. Amblyopia is a result of aberrant stimulation of the brain during the critical periods of brain plasticity and visual development [2, 3]. Unilateral amblyopia is defined as ≥2-line difference in the BCVA between both eyes with a BCVA of 20/32 (0.2 logMAR) or less in the affected eye, having an amblyogenic factor that explains the weakness. Bilateral amblyopia is a deficit in BCVA of <20/40(0.3 logMAR) bilaterally for ages 48 to 72 months, or <20/50 (0.4 logMAR) bilaterally for ages <48 months, having an amblyogenic factor in both eyes that explains the weakness [6]. If not treated, amblyopia can cause low vision that persists throughout adulthood.

Amblyopia is the leading cause of unilateral low vision, affecting 1-5% of the world population [2, 7]. The high prevalence leads to widespread disability, with significant financial efforts directed towards its prevention and treatment. In addition to the economic impact, individuals with amblyopia often have reduced quality of life, including limited career options, minimized social interaction, and anxiety towards losing vision in the contralateral eye [2].

Amblyopia may be classified according to its main etiological factor: strabismic, deprivational, refractive (anisometropic or ametropic), or a mix of more than one. Strabismus is the misalignment of both eyes which results in different images on the fovea, leading to unilateral amblyopia [8]. Anisometropia, defined as the difference in refractive error between both eyes of ≥1.50 D difference in hypermetropia, ≥3.00 D difference in myopia, or ≥1.50 D difference in astigmatism in any meridian leading to one foveal image being more blurred than the other leading to unilateral amblyopia. Ametropia is described as hypermetropia ≥4.00 D, myopia ≥ 6.00 D, or astigmatism ≥ 2.50 D that can induce either unilateral or bilateral amblyopia. Deprivational amblyopia is usually due to evidence of past or present obstruction of the visual axes including cataract or ptosis among other causes [6, 8].

The conventional treatment options of amblyopia in children include refractive correction, patching, or penalization using pharmacological agents [1, 9]. Refractive correction alone improves visual acuity and resolves amblyopia in at least one third of 3 to 7-year-olds with anisometric amblyopia. It is important to note the cases which resolve usually have moderate (0.3 to 0.7 logMAR) amblyopia, nevertheless treating the more advanced levels of amblyopia with glasses decreases the burden of the subsequent therapy [9]. When refractive correction alone does not restore normal vision in the amblyopic eye, patching the contralateral eye is necessary. Covering the fellow eye reduces neural stimulation of areas devoted to input from the normal eye, as depicted in experimental animal studies [10]. Consequently, this will increase reliance on visual input, and firing of neural pathways of the amblyopic eye. Over time neuronal plasticity will rearrange the cortical ocular dominance columns if early enough, or lead to less functional suppression. Compliance with patching is usually suboptimal for many reasons like child’s compliance, skin irritation due to the patch and relying on the vision of the normal eye commonly outweigh the enthusiasm of the patients and their parents to protect themselves from the consequences of not treating amblyopia [11]. Penalization of the unaffected eye with 1% atropine solution causes cycloplegia, preventing it from focusing. This method is used as a substitute or in addition to patching for treatment of mild to moderate amblyopia, if the healthy eye is hyperopic. However, penalization has been associated with photosensitivity [12] and systemic adverse effects of atropine: dry mouth, tachycardia, and delirium [13].

Initially the resolution of amblyopia was noted to be limited to the age in which treatment began, due to the “critical period” of brain plasticity. Optimal efficacy of patching was reported before 3 years and the efficiency was decreased until negligible by 12 years of age [14]. However, recent studies have reported plasticity in the visual cortex in adult amblyopic patients past the critical period [15]. Transient enhancement of contrast sensitivity in the amblyopic visual cortex, and improvement in letter recognition tasks with repetitive transcranial magnetic stimulation (rTMS) have been noted in adults [16, 17]. Moreover, it has been observed that the window of plasticity may be reopened beyond the critical period with a short decrease of the gamma-aminobutyric acid-ergic (GABAergic) inhibition in rats [18]. Multiple intrinsic and extrinsic means of enhancing plasticity to increase efficacy in treating amblyopia post critical period have been investigated. Intrinsic methods include perceptual learning with demanding visual tasks to stimulate the manipulation of endogenous neurotransmitters in the brain. On the other hand, extrinsic augmentation uses external approaches, which include levodopa, to modulate the internal neurotransmitters to improve neuronal plasticity. However, it is worth pointing out that clinical studies have shown that there is no statistical significance in visual acuity improvement between those given levodopa and those on placebo. Development of the visual system continues throughout adolescence, during a time known as the critical period. Proper development relies on 3 fundamental conditions: adequate stimuli reaching retinal photoreceptors of each eye, ocular parallelism, and integrity of visual pathways [19]. Lastly, animal studies promote valproate’s use as a histone deacetylase inhibitor to modify gene expression, reversing the “brakes” on neural plasticity [19]. Fortunately, this implies that the adult visual system may still have capacity for functional recovery. 

Laser refractive surgeries for correction of amblyopia is engrossing and evolving. Laser therapies are well tolerated, have low complication rates and have validated BCVA gains [20]. Regression is a common concern across with preoperative refractory errors, and mostly happens during the first year following surgery with smaller shifts in next 2-3 years. Anticipating these shifts, overcorrection by 1-2D may be a pragmatic approach. Anecdotal reports suggest application of antimetabolite mitomycin-c (MMC) has to reduce regression in both myopic and hypermetropic treatment [21]. Therefore, refractive surgery is a feasible option for children with refractive amblyopia who are non-compliant with spectacle wear or non-responsive to traditional treatment. In children with neurobehavioral disorders, correction of ametropia with PRK (Photorefractive keratectomy) and Phakic IOL have demonstrated significant improvement in vision and outcomes in global functioning. These strategies need further affirmation with randomized control studies. Currently PEDIG (pediatric eye disease investigation group) is planning Amblyopia Treatment study 19, intended to compare PRK versus non-surgical treatment of anisometric amblyopia in children who have failed conventional treatment [22].  Results from this trial may provide further evidence in support of refractive surgery in the management of amblyopia. As most of the research pertaining to these topic is limited to pediatric population, our study is to evaluate the effects of laser refractive surgery in adult patients with amblyopia due to strabismus, refractive error, or both. Our study will be the first study to prove the efficacy of laser assisted Subepithelial Keratectomy (LASEK) in this patient population.