The relationship between anisometropia and amblyopia

Abstract

This review aims to disentangle cause and effect in the relationship between anisometropia and amblyopia. Specifically, we examine the literature for evidence to support different possible developmental sequences that could ultimately lead to the presentation of both conditions. The prevalence of anisometropia is around 20% for an inter-ocular difference of 0.5D or greater in spherical equivalent refraction, falling to 2-3%, for an inter-ocular difference of 3D or above. Anisometropia prevalence is relatively high in the weeks following birth, in the teenage years coinciding with the onset of myopia and, most notably, in older adults starting after the onset of presbyopia. It has about one-third the prevalence of bilateral refractive errors of the same magnitude. Importantly, the prevalence of anisometropia is higher in highly ametropic groups, suggesting that emmetropization failures underlying ametropia and anisometropia may be similar. Amblyopia is present in 1-3% of humans and around one-half to two-thirds of amblyopes have anisometropia either alone or in combination with strabismus. The frequent co-existence of amblyopia and anisometropia at a child's first clinical examination promotes the belief that the anisometropia has caused the amblyopia, as has been demonstrated in animal models of the condition. In reviewing the human and monkey literature however it is clear that there are additional paths beyond this classic hypothesis to the co-occurrence of anisometropia and amblyopia. For example, after the emergence of amblyopia secondary to either deprivation or strabismus, anisometropia often follows. In cases of anisometropia with no apparent deprivation or strabismus, questions remain about the failure of the emmetropization mechanism that routinely eliminates infantile anisometropia. Also, the chronology of amblyopia development is poorly documented in cases of 'pure' anisometropic amblyopia. Although indirect, the therapeutic impact of refractive correction on anisometropic amblyopia provides strong support for the hypothesis that the anisometropia caused the amblyopia. Direct evidence for the aetiology of anisometropic amblyopia will require longitudinal tracking of at-risk infants, which poses numerous methodological and ethical challenges. However, if we are to prevent this condition, we must understand the factors that cause it to develop.

Keywords: Amblyopia; Anisometropia; Anisometropic amblyopia; Emmetropization; Refractive error; Visual development.

Figure 1

Number of publications about ‘anisometropic amblyopia’ per decade, identified using PubMed searches. [Search conducted, July 1^st, 2012].

Figure 2

Dependence of prevalence on the criterion used to diagnose anisometropia. Anisometropia is given as the inter-ocular difference in spherical-equivalent refractive error. Results are shown from studies that quoted prevalence figures using different criteria in a single sample. (Cheng et al., 2003; Chia, 2010; Deng and Gwiazda, 2012; Giordano et al., 2009; Gupta et al., 2008; Guzowski et al., 2003; Huynh et al., 2006; Ohlsson et al., 2003; Qin et al., 2005; Quek et al., 2004; Saw et al., 2002; Tarczy-Hornoch et al., 2011; Tong et al., 2004).

Figure 3

Prevalence of anisometropia as a function of age. To account for differences in criterion used to diagnose anisometropia, only studies employing the most commonly used criterion are included, a difference of 1D or greater in spherical equivalent refraction between the right and left eyes.

Figure 4

Prevalence of amblyopia (%) as a function of the magnitude of anisometropia (D). Positive values on the abscissa indicate anisohyperopia, negative values represent anisomyopia. Studies were included only if they reported on individuals without manifest strabismus and if they distinguished between cases anisomyopia and anisohyperopia. Studies were not included if the whole sample was amblyopic (e.g. Townshend et al., 1993; Kutschke et al., 1991). The criteria for diagnosis of amblyopia are those that appeared in the respective studies.

Figure 5

Severity of amblyopia (logMAR VA) as a function of magnitude of anisometropia (D). Positive values on the abscissa indicate anisohyperopia, negative values represent anisomyopia. Studies were included only if they reported on individuals without manifest strabismus and if they distinguished between cases anisomyopia and anisohyperopia.

Figure 6

Hypothesis 1 is the standard clinical explanation: something causes emmetropiziation to fail, and chronic, unilateral blurring from anisometropia causes the amblyopia. Hypothesis 2: the anisometropia is caused by the amblyopia. Hypothesis 3: the amblyopia and the anisometropia are not linked causally but are both triggered by a third factor. Hypotheses 2 and 3 are theoretically distinct but they are difficult to distinguish because amblyopia tends to arise quickly following deprivation whereas anisometropia onset and progression is much slower (see section 4.1). Thus, even if Hypothesis 3 is correct, the earlier appearance of the amblyopia could falsely be interpreted as evidence that the amblyopia has caused the anisometropia (Hypothesis 2). Cases of “pure ” anisometropic amblyopia (where there is no apparent triggering factor) are believed to represent instances where the anisometropia has caused the amblyopia (Hypothesis 1) but Hypotheses 2 or 3 may be correct if a sub-clinical anomaly exists now or if one existed in the past.