Anisometropia is a condition in which the refractive error differs between the two eyes. A difference in spherical equivalent refraction of 1.00 diopter (D) or greater between both eyes is usually used as the definition for anisometropia.1
Anisometropia is an infrequent finding in the population. The prevalence of anisometropia (difference in spherical equivalent refraction ≥ 1.00 D) is low (≤ 18%) before 40 years and most studies report a prevalence of lower than 10%.2,3 However, prevalence of anisometropia is thought to be age dependent, with a relatively low prevalence among young children and a higher prevalence among adults.1–6 Several longitudinal studies show that anisometropia increases after children start school.7–9 Moreover, a study in Japan found a small increase in the prevalence of spherical anisometropia (spherical difference ≥ 1.00 D), rising from 1.43% at 6 years to 3.14% at 11 years.10
Whereas lower degrees of anisometropia are usually tolerated well with glasses, children with higher degrees of anisometropia (≥ 4.00 D) are more likely to develop amblyopia during their preschool years and symptoms become more difficult to manage.11 Refractive surgery has been suggested as a possible method of management for such patients to minimize aniseikonia and improve visual acuity.12–14 However, because the onset and progression of such large differences in refraction between the two eyes is not clearly known, the choice of the age at surgery and the accurate interpretation of the refractive stability after refractive surgery is always biased by the possible age-related refractive changes in such an age group. Our study aimed to analyze the stability and progression of higher degrees of myopic anisometropia in children.
Patients and Methods
A retrospective study was performed to evaluate the progression of myopic anisometropia in children younger than 13 years examined in the pediatric ophthalmology outpatient clinic between June 2004 and January 2015. Children with myopic anisometropia, myopia of greater than 4.00 D in the more ametropic eye, and a difference in spherical equivalent refraction of 4.00 D or greater between both eyes at any visit were included in the study. Children were included only if they completed follow-up for at least 5 consecutive years. Exclusion criteria included evidence of intraocular pathology or prior intraocular surgeries. The study was approved by the Cairo University Research Ethics Committee and followed the tenets of the Declaration of Helsinki.
All patients included in the study had a complete ophthalmologic examination, including measurement of visual acuity, cycloplegic refraction, detailed slit-lamp examination, and dilated fundus examination during each visit. Ductions and versions were evaluated in all patients. A cover–uncover test was performed for both a near accommodative and distant target to detect any heterotropia or phoria in the primary position.
Uncorrected and best corrected distance visual acuity was measured with a single surround HOTV letter using a standard commercial chart projector. Cycloplegic refraction was done using 1% cyclopentolate instilled three times 10 minutes apart. The last instillation of the drops was 30 to 45 minutes before refraction. Refraction was done using both objective streak retinoscopy and subjective refinement, whenever appropriate. However, only the objective measurements were used to standardize the measurements for statistical analysis.
All patients were prescribed spectacles based on the results of either the cycloplegic refraction or the subjective refinement. Astigmatism and myopia were corrected fully in both eyes. If the less ametropic eye was hypermetropic, hypermetropia was undercorrected by 0.50 to 1.00 D.
Follow-up with patients was scheduled every 3 to 6 months. Patients with amblyopia, defined as a difference of three or more lines of visual acuity (logarithm of the minimum angle of resolution) between both eyes, started amblyopia therapy using standard guidelines (2 hours of daily patching for moderate amblyopia and 6 hours of daily patching for severe amblyopia). Amblyopia therapy was continued whenever possible until the difference in visual acuity was one line or less between both eyes.
The age of the patients at presentation and the initial presentation was recorded. Changes in the spherical equivalent and cylindrical error for both eyes and in the difference in the spherical equivalent between both eyes were calculated for each patient at each visit. For statistical calculations, linear, polynomial, logarithmic, and exponential fitting models were tested for the more ametropic and the less ametropic eye, as well as for the anisometropic difference between both eyes. The regression line with the greatest R2 value was considered best fit.
A total of 418 patients diagnosed as having myopic anisometropia were identified. Of these patients, only 63 patients fulfilled the inclusion criteria. The rest were excluded because of an insufficient follow-up period or because the difference in the spherical equivalent between both eyes was less than 4.00 D.
The mean age of these patients at the initial visit was 4.3 years. Most patients were accidentally discovered during routine eye examinations at school or ophthalmology consultations. The most common age at presentation was 4 to 6 years. A summary of the clinical characteristics of the patients is presented in Table 1.
Clinical Characteristics of Patients
The mean spherical equivalent and cylinder at presentation and at the last follow-up are presented in Table 2. The best corrected visual acuity was statistically significantly lower in the more ametropic eye at presentation. Although the best corrected visual acuity improved significantly throughout the study period (P < .01), it remained statistically significantly lower in the more ametropic eye at the last follow-up. The percentage of patients who satisfied the definition of amblyopia decreased significantly throughout the study period (P < .01). However, 68% of the patients continued to satisfy the definition of amblyopia at the last follow-up visit.
Refraction and Visual Acuity of Patients at Presentation and the Last Follow-Up
During the study period, the more ametropic eye seemed to grow in a regular fashion as monitored by cycloplegic refraction during the first 2 years of life, followed by a rapid decrease in the rate of growth, so that refractive changes were minimal after 4 years of age (Figure 1). The increase in myopia best fit a third-degree polynomial (cubic) model. A dioptric diagram of the mean cycloplegic refraction in the more ametropic eye is summarized by the following polynomial function: cycloplegic = −0.0158x3 + 0.3545x2 − 2.5863x + 6.1426, where x is patient age in years and R2 = 0.98.
Scatter plot showing the mean change in spherical equivalent refraction in both the more ametropic and the less ametropic eye during follow-up. The increase in myopia in the more ametropic eye best fit a third-degree polynomial (cubic) model (R2 = 0.98) with an initial increase in myopia during the first 2 years of life followed by a rapid decrease in the rate of growth, so that the increase in myopia was minimal after 4 years of life. The less ametropic eye best fit a linear model with a small increase in the rate of increase in myopia with increasing age. D = diopters
A second-degree polynomial model proved to be a good match during the initial study period, but did not explain the trend of a rapid decrease in rate of growth toward the end of the study period. The exponential model tended to underestimate the rate of myopic progression when the children were younger. The regression curves of the cycloplegic refraction during follow-up for the population sample are shown in Figure 2.
Scatter plots showing different regression models for the mean change in spherical equivalent refraction in the more ametropic eye during follow-up. D = diopters
Regardless of how low (spherical equivalent refraction > 4.00 and < 6.00 D), intermediate (spherical equivalent refraction ≥ 6.00 and < 8.00 D), or high (spherical equivalent refraction ≥ 8.00 D) initial refraction was, the curves were, to a large extent, parallel to the mean curve (Figure 3).
Scatter plots showing the mean change in spherical equivalent refraction (SER) in the more ametropic eye based on the initial refraction. D = diopters
The less ametropic eye showed only a small increase in myopia during the follow-up period (Figure 1). The increase in myopia best fit a linear model with a small increase in the rate of increase in myopia with increasing age.
The anisometropic difference between both eyes increased gradually during the first 2 years of life, then remained stable during the follow-up period. Toward the end of the follow-up period, there was a small clinically nonsignificant decrease in the anisometropic difference.
Of the 63 patients, only 3 eyes deviated from the general pattern. In one eye, there was a slow continuous increase in the progression of myopia in the more ametropic eye until 6 years of age (case 24). In two other patients (cases 31 and 53), there was a progression of myopia in the less ametropic eye at a higher rate that started at 9 years of age and resulted in a decrease in the amount of anisometropia.
Although there is substantial evidence of the axial nature of anisometropia,15–17 little is known about what initially triggers mismatched eye growth. Furthermore, the possible association of myopia and the development of anisometropia are topics of interest.
In school-aged children, special interest has been drawn to the association between myopia progression and the development of anisometropia.2,10 The cause-and-effect relationship between myopia and anisometropia remains unknown, given that few longitudinal studies are available to investigate the question in depth.10
Pärssinen8 examined the change in anisometropia during a period of 3 years in school-aged myopic children participating in a lens treatment study. An increase in the prevalence of significant anisometropia (≥ 1.00 D) from 8% to 18% after 3 years of myopia progression was found. Pärssinen also observed a small but significant correlation (r = 0.13) between myopia progression and the increase in anisometropia. However, no correlation between the magnitude of anisometropia at baseline and the amount of myopia progression was found.8 Another longitudinal study,9 conducted in Singapore, reported an increase in the prevalence of anisometropia from 3.6% to 9.9% after 3 years in children with a baseline age between 7 and 9 years and faster myopia progression rates in those with anisometropia (defined as being anisometropic at any visit) versus those without anisometropia.
In the current study, large degrees of anisometropia (≥ 4.00 D) at an early age had little influence on the progression of myopia after 4 years and up to 13 years, suggesting that large degrees of anisometropia are not a risk factor for the progression of myopia after 4 years of age. We found that both the more anisometropic and the less ametropic eyes maintained a stable refraction throughout childhood, even in the presence of anisometropia during the early years.
Preschool refractive error screening could detect many children with amblyogenic levels of anisometropia and most studies show an increased risk of amblyopia with anisometropia of greater than 1.00 D.9,11 All of our patients had high anisometropia. It is not surprising that, even after occlusion and optical correction with glasses, most patients had persistent amblyopia.
Large degrees of anisometropia prevent the development of binocular single vision and are associated with a high risk of amblyopia. In addition, it may be refractory to treatment because of noncompliance with spectacle or contact lens wear.11 Although refractive surgery for anisometropic children seems like a valid option to achieve symmetry between both eyes, it has risks and may cause refractive instability in children.12–14 In the current study, most anisometropia progression occurred in the first few years of life, with little change in the amount of anisometropia afterward. However, we did not study the refractive stability after 13 years. Refractive changes may be expected to occur afterward, especially with hormonal changes associated with puberty.
Limitations of the study include its retrospective nature and the relatively small number of patients included. This is partly because of the strict inclusion criteria. A prospective longitudinal study addressing the progression of refractive changes since the first year of life would provide more reliable data. Unfortunately, most children with anisometropia are diagnosed at a later age, which makes recruitment of patients difficult.
High anisometropic myopia progresses rapidly in the first few years of life before becoming stable. Although older children may present with large myopic anisometropic refraction, this difference is probably present before 4 years of age. Changes in spherical equivalent refraction between both eyes in the following years are insignificant.
- Deng L, Gwiazda JE. Anisometropia in children from infancy to 15 years. Invest Ophthalmol Vis Sci. 2012;53:3782–3787. doi:10.1167/iovs.11-8727 [CrossRef]
- Almeder LM, Peck LB, Howland HC. Prevalence of anisometropia in volunteer laboratory and school screening populations. Invest Ophthalmol Vis Sci. 1990;31:2448–2455.
- Hashemi H, Khabazkhoob M, Yekta A, Mohammad K, Fotouhi A. Prevalence and risk factors for anisometropia in the Tehran eye study, Iran. Ophthalmic Epidemiol. 2011;18:122–128. doi:10.3109/09286586.2011.574333 [CrossRef]
- Borchert M, Tarczy-Hornoch K, Cotter SA, et al. Anisometropia in Hispanic and African American infants and young children: the multi-ethnic pediatric eye disease study. Ophthalmology. 2010;117:148–153. doi:10.1016/j.ophtha.2009.06.008 [CrossRef]
- Dobson V, Harvey EM, Miller JM, Clifford-Donaldson CE. Anisometropia prevalence in a highly astigmatic school-aged population. Optom Vis Sci. 2008;85:512–519. doi:10.1097/OPX.0b013e31817c930b [CrossRef]
- Huynh SC, Wang XY, Ip J, et al. Prevalence and associations of anisometropia and aniso-astigmatism in a population based sample of 6 year old children. Br J Ophthalmol. 2006;90:597–601. doi:10.1136/bjo.2005.083154 [CrossRef]
- Abrahamsson M, Fabian G, Sjöstrand J. A longitudinal study of a population based sample of astigmatic children: II. The changeability of anisometropia. Acta Ophthalmol (Copenh). 1990;68:435–440. doi:10.1111/j.1755-3768.1990.tb01672.x [CrossRef]
- Pärssinen O. Anisometropia and changes in anisometropia in school myopia. Optom Vis Sci. 1990;67:256–259. doi:10.1097/00006324-199004000-00005 [CrossRef]
- Tong L, Chan YH, Gazzard G, Tan D, Saw SM. Longitudinal study of anisometropia in Singaporean school children. Invest Ophthalmol Vis Sci. 2006;47:3247–3252. doi:10.1167/iovs.05-0906 [CrossRef]
- Yamashita T, Watanabe S, Ohba N. A longitudinal study of cycloplegic refraction in a cohort of 350 Japanese schoolchildren: anisometropia. Ophthalmic Physiol Opt. 1999;19:30–33. doi:10.1046/j.1475-1313.1998.00407.x [CrossRef]
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Clinical Characteristics of Patients
|Mean age at presentation ± SD (range)||4.3 years ± 2.0 (range: 0 to 8 years)|
|Male/female sex||32 (51%) / 31 (49%)|
|Right eye/left eye||33 (52%) / 30 (48%)|
| Accidentally discovered||40 (63%)|
| Visual troubles||12 (19%)|
| Strabismus (exotropia)||11 (17%)|
|Age at presentation (y)|
| < 2||10 (16%)|
| ≥ 2 to < 4||15 (24%)|
| ≥ 4 to < 6||27 (43%)|
| ≥ 6 to < 8||10 (16%)|
| ≥ 8 to < 10||1 (2%)|
|Mean follow-up ± SD (range)||5.6 ± 0.9 (5 to 8 years)|
Refraction and Visual Acuity of Patients at Presentation and the Last Follow-Upa
|Variable||At Presentation||At Last Follow-Up|
|More Ametropic Eye||Less Ametropic Eye||P||More Ametropic Eye||Less Ametropic Eye||P|
|Spherical equivalent (D)||−7.81 ± 2.75 (range: −2.175 to −11.25)||−0.14 ± 1.45 (range: −2.12 to +1.75)||< .01||−8.81 ± 2.36 (range: −4.13 to −12.25)||−0.93 ± 1.89 (range: −5.25 to +1.63)||< .01|
|Cylindrical error mean (D)||2.04 ± 1.12 (range: 0.25 to 4.50)||1.32 ± 0.89 (range: 0.00 to 2.75)||.03||2.24 ± 0.98 (range: 0.50 to 4.50)||1.45 ± 0.95 (range: 0.00 to 3.00)||.03|
|logMAR BCVA (D)||0.72 ± 0.19 (range: 1.00 to 0.52)||0.03 ± 0.04 (range: 0.10 to 0.00)||< .01||0.47 ± 0.31 (range: 1.00 to 0.10)||0.02 ± 0.04 (range: 0.10 to 0.00)||< .01|
|No amblyopia||61 (97%)||–||–||43 (68%)||–||–|