Purpose
To determine the frequency of unilateral amblyopia in right versus left eyes among children younger than 18 years.
Design
Analysis of data collected in randomized clinical trials conducted by the Pediatric Eye Disease Investigator Group.
Methods
The laterality of the amblyopic eye was analyzed in 2635 subjects younger than 18 years who participated in 9 multicenter prospective, randomized treatment trials. Eligibility criteria for these clinical trials included unilateral amblyopia associated with strabismus, anisometropia, or both, with visual acuity between 20/40 and 20/400. Logistic regression was used to assess the association of baseline and demographic factors with the laterality of amblyopia.
Results
Among subjects with anisometropic amblyopia (with or without strabismus), amblyopia was present more often in left than right eyes, with a relative prevalence of 59% in left eyes (95% confidence interval, 57% to 62%; P < .001 from a test of proportion, 50%). However, among subjects with strabismic-only amblyopia, there was no laterality predilection (relative prevalence of 50% in left eyes; 95% confidence interval, 47% to 54%; P = .94).
Conclusions
Anisometropic amblyopia, with or without strabismus, occurs more often in left eyes than right eyes. This finding of amblyopia laterality may be related to microtropia, sighting dominance, or other forms of ocular dominance; developmental or neurological factors; laterality in the development of refractive error; or a combination thereof.
Among individuals with amblyopia, reduced visual acuity typically is present in 1 eye. Several retrospective reports suggest that amblyopia occurs more often in left eyes ( Table 1 ). This study examined the laterality of amblyopia among children younger than 18 years enrolled in prospective amblyopia studies conducted by the Pediatric Eye Disease Investigator Group (PEDIG).
| Study | No. | Type | Left Eye Prevalence (95% Confidence Interval) |
|---|---|---|---|
| Cole, 1959 | 527 | M | 58% (53% to 62%) |
| Coren and Duckman, 1975 | 258 | S | 57% (51% to 63%) |
| Hopkisson and associates, 1982 | 379 | M | 53% (48% to 58%) |
| Attebo and associates, 1998 | 118 | M | 53% (44% to 63%) |
| Woodruff and associates, 1994 | 164 | A | 64% (56% to 71%) |
| 262 | C | 56% (50% to 62%) | |
| 535 | S | 53% (49% to 57%) | |
| Total | 2243 | — | 56% (54% to 58%) |
Methods
The patient population for this report was drawn from 9 randomized, multicenter clinical trials. The protocols are available on the PEDIG web site ( www.pedig.net ). Two thousand six hundred thirty-five subjects, ranging in age from 2 to 17 years, with unilateral amblyopia (20/40 and 20/400; 0.3 and 1.3 logarithm of the minimum angle of resolution units) associated with strabismus, anisometropia, or both were enrolled. Specific eligibility criteria varied by study. For each patient, amblyopia was classified by presumptive cause into 1 of 3 categories. Strabismic amblyopia required the presence of (1) either a heterotropia at distance or near fixation, or both, or a history of strabismus surgery (or botulinum toxin injection); and (2) refractive error not meeting the criteria below for combined mechanism amblyopia. Refractive or anisometropic amblyopia (referred to subsequently as anisometropic amblyopia without strabismus ) required the presence of anisometropia of 0.50 diopters (D) or more of spherical equivalent or 1.50 D or more difference in astigmatism in any meridian that persisted after at least 4 weeks of spectacle correction, with no measurable heterotropia at distance or near fixation. Eligibility criteria specified that the amblyopic eye be the more hypermetropic eye. Combined mechanism amblyopia (referred to herein as anisometropic amblyopia with strabismus ) required the presence of (1) either a heterotropia at distance or near fixation, or both, or a history of strabismus surgery (or botulinum toxin injection); and (2) anisometropia of 1.00 D or more of spherical equivalent or 1.50 D or more difference in astigmatism in any meridian, which persisted after at least 4 weeks of spectacle correction.
Statistical Methods
The proportion of subjects with amblyopia in their left eyes and the corresponding 95% confidence interval was calculated overall and in subgroups based on baseline factors, including cause of amblyopia, age at randomization (younger than 7 years vs 7 to younger than 18 years), race (white vs nonwhite), and severity of amblyopia (amblyopic eye visual acuity 20/100 or better vs 20/125 or worse). The analysis consisted of an exact binomial test evaluating the null hypothesis that the proportion of cases with the left eye affected was 0.50. A multivariate logistic regression analysis was used to explore whether amblyopic eye laterality differed with respect to the baseline factors above while adjusting for the other baseline factors (with cause of amblyopia and race as categorical variables, and age and severity of amblyopia registered as continuous variables).
Among subjects with anisometropic amblyopia with or without strabismus, the multivariate logistic model was repeated to include the amount of anisometropia (continuous) and the amount of hyperopia in the amblyopic eye (continuous), in addition to age, race, and amblyopic eye visual acuity.
Results
Among 2635 subjects with unilateral amblyopia, 56.6% of amblyopic eyes were left eyes (95% confidence interval, 54.7% to 58.5%; P < .001 from test of proportion, 50%; Table 2 ). Laterality was associated with the presence of anisometropic amblyopia with or without strabismus ( P < .001). Among subjects with anisometropic amblyopia (747 subjects with strabismus and 1071 without strabismus), amblyopia was present more often in left than right eyes, with a relative prevalence of 59% in left eyes (95% confidence interval, 56% to 62%; P < .001 from a test of proportion, 50%), whereas among subjects with strabismic-only amblyopia (n = 817), there was no laterality predilection (relative prevalence of 50% in left eyes; 95% confidence interval, 47% to 54%; P = .94). There was no significant difference in the laterality of the anisometropic patients when comparing those with strabismus with those without strabismus (61% vs 59%; P = .68).
| No. | Left Eye Percentage | P Value a | |
|---|---|---|---|
| Race | .96 | ||
| White | 1533 | 60% | |
| Nonwhite | 285 | 58% | |
| Age at enrollment (yrs) | .33 | ||
| <5 | 470 | 61% | |
| 5 to <7 | 815 | 58% | |
| 7 to <9 | 211 | 60% | |
| 9 to < 12 | 213 | 60% | |
| 12 to <15 | 80 | 63% | |
| 15 to <18 | 29 | 62% | |
| Visual acuity in the amblyopic eye | .66 | ||
| 20/100 or better (≥48 letters) | 1448 | 59% | |
| 20/125 or worse (≤47 letters) | 370 | 61% | |
| Amount of hypermetropia in amblyopic eye (D) | <.001 | ||
| <+2.00 | 180 | 46% | |
| +2.00 to <+4.00 | 390 | 55% | |
| ≥+4.00 | 1248 | 63% | |
| Amount of anisometropia (D) | .47 | ||
| <+1.00 | 333 | 55% | |
| +1.00 to <+2.00 | 631 | 59% | |
| +2.00 to <+3.00 | 337 | 59% | |
| +3.00 to <+4.00 | 248 | 61% | |
| ≥+4.00 | 269 | 64% |
a From a multivariate logistic regression analysis evaluating the association of amblyopic eye predominance with race, age at enrollment, amblyopic eye acuity, amblyopic eye refractive error, and degree of anisometropia. All covariates were included in the model as continuous variables other than race.
Among subjects with anisometropic amblyopia with or without strabismus, there was no apparent relationship of laterality with age ( P = .33), race ( P = .96), or amblyopia severity ( P = .66). The degree of anisometropia was not associated with laterality ( P = .47); however, there was an increased likelihood of the left eye being amblyopic with increasing hypermetropia in the amblyopic eye ( P < .001; Table 2 ).
Results
Among 2635 subjects with unilateral amblyopia, 56.6% of amblyopic eyes were left eyes (95% confidence interval, 54.7% to 58.5%; P < .001 from test of proportion, 50%; Table 2 ). Laterality was associated with the presence of anisometropic amblyopia with or without strabismus ( P < .001). Among subjects with anisometropic amblyopia (747 subjects with strabismus and 1071 without strabismus), amblyopia was present more often in left than right eyes, with a relative prevalence of 59% in left eyes (95% confidence interval, 56% to 62%; P < .001 from a test of proportion, 50%), whereas among subjects with strabismic-only amblyopia (n = 817), there was no laterality predilection (relative prevalence of 50% in left eyes; 95% confidence interval, 47% to 54%; P = .94). There was no significant difference in the laterality of the anisometropic patients when comparing those with strabismus with those without strabismus (61% vs 59%; P = .68).
| No. | Left Eye Percentage | P Value a | |
|---|---|---|---|
| Race | .96 | ||
| White | 1533 | 60% | |
| Nonwhite | 285 | 58% | |
| Age at enrollment (yrs) | .33 | ||
| <5 | 470 | 61% | |
| 5 to <7 | 815 | 58% | |
| 7 to <9 | 211 | 60% | |
| 9 to < 12 | 213 | 60% | |
| 12 to <15 | 80 | 63% | |
| 15 to <18 | 29 | 62% | |
| Visual acuity in the amblyopic eye | .66 | ||
| 20/100 or better (≥48 letters) | 1448 | 59% | |
| 20/125 or worse (≤47 letters) | 370 | 61% | |
| Amount of hypermetropia in amblyopic eye (D) | <.001 | ||
| <+2.00 | 180 | 46% | |
| +2.00 to <+4.00 | 390 | 55% | |
| ≥+4.00 | 1248 | 63% | |
| Amount of anisometropia (D) | .47 | ||
| <+1.00 | 333 | 55% | |
| +1.00 to <+2.00 | 631 | 59% | |
| +2.00 to <+3.00 | 337 | 59% | |
| +3.00 to <+4.00 | 248 | 61% | |
| ≥+4.00 | 269 | 64% |
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