Association of Axial Length With Risk of Uncorrectable Visual Impairment for Europeans With Myopia

Question  What is the association between axial length, refractive error, and risk of visual impairment？

Findings  In this cross-sectional study of data from several population-based studies and a case-control study in the Netherlands, axial lengths of 26 mm and greater and refractive errors of −6 diopters and less were significantly associated with an increased lifetime risk of visual impairment.

Meaning  Extrapolating these results to regions that have recently experienced a strong rise in myopia indicates that myopia will become the most important cause of blindness.

Importance  Myopia (ie, nearsightedness) is becoming the most common eye disorder to cause blindness in younger persons in many parts of the world. Visual impairment due to myopia is associated with structural changes of the retina and the globe because of elongation of the eye axis. How axial length—a sum of the anterior chamber depth, lens thickness, and vitreous chamber depth—and myopia relate to the development of visual impairment over time is unknown.

Objectives  To evaluate the association between axial length, spherical equivalent, and the risk of visual impairment and to make projections of visual impairment for regions with high prevalence rates.

Design, Setting, and Participants  This cross-sectional study uses population-based data from the Rotterdam Study I (1990 to 1993), II (2000 to 2002), and III (2006 to 2008) and the Erasmus Rucphen Family Study (2002 to 2005) as well as case-control data from the Myopia Study (2010 to 2012) from the Netherlands. In total, 15 404 individuals with data on spherical equivalent and 9074 individuals with data on axial length were included in the study; right eyes were used for analyses. Data were analyzed from September 2014 to May 2016.

Main Outcomes and Measures  Visual impairment and blindness (defined according to the World Health Organization criteria as a visual acuity less than 0.3) and predicted rates of visual impairment specifically for persons with myopia.

Results  Of the 15 693 individuals included in this study, the mean (SD) age was 61.3 (11.4) years, and 8961 (57.1%) were female. Axial length ranged from 15.3 to 37.8 mm; 819 individuals had an axial length of 26 mm or greater. Spherical equivalent ranged from −25 to +14 diopters; 796 persons had high myopia (ie, a spherical equivalent of −6 diopters or less). The prevalence of visual impairment varied from 1.0% to 4.1% in the population-based studies, was 5.4% in the Myopia Study, and was 0.3% in controls. The prevalence of visual impairment rose with increasing axial length and spherical equivalent, with a cumulative incidence (SE) of visual impairment of 3.8% (1.3) for participants aged 75 years with an axial length of 24 to less than 26 mm and greater than 90% (8.1) with an axial length of 30 mm or greater. The cumulative risk (SE) of visual impairment was 5.7% (1.3) for participants aged 60 years and 39% (4.9) for those aged 75 years with a spherical equivalent of −6 diopters or less. Projections of these data suggest that visual impairment will increase 7- to 13-fold by 2055 in high-risk areas.

Conclusions and Relevance  This study demonstrated that visual impairment is associated with axial length and spherical equivalent and may be unavoidable at the most extreme values in this population. Developing strategies to prevent the development of myopia and its complications could help to avoid an increase of visual impairment in the working-age population.

Myopia (ie, nearsightedness) is a common refractive error and is generally considered a nonthreatening condition that can be corrected with eyewear, contact lenses, or refractive surgical procedures. Nonetheless, the incidence of myopia has increased rapidly during the past 30 years, predominantly in East Asia.1-4 The trait results from excessive growth of the eyes’ axial length, which is a sum of the anterior chamber depth, lens thickness, and vitreous chamber depth.5-7 High myopia is defined as a spherical equivalent of −6 diopters (D) or less with an axial length generally exceeding 26 mm.8 The frequency of high myopia in the general population is estimated to be 3% to 20%.3,9-11

High myopia is currently one of the leading causes of legal blindness in developed countries because of complications occurring in adulthood, such as myopic macular degeneration, early cataract, retinal detachment, and/or glaucoma.11 The rapid increase in prevalence combined with the sight-threatening complications represents a significant public health burden.12,13 Studies addressing the association between myopia and ocular pathology found that few eyes with mild to moderate myopia develop ocular pathology in contrast to many eyes with high myopia.14-18 From this, it seems a logical assumption that a longer axial length is associated with higher risks of visual impairment.16,19,20 Nevertheless, to our knowledge, precise risk estimates of the association between axial length and lifetime visual function are currently lacking.

In this study, we investigated the association between axial length, spherical equivalent, and visual impairment as a function of age. We combined epidemiologic studies from the same research center to maximize the number of persons with very long axial lengths and high spherical equivalents and to achieve sufficient statistical power for lifetime analyses. Next, we extrapolated our risk estimates to make a prediction of the rise in visual impairment in regions that have recently experienced a high increase in myopia prevalence. The goal of our study was to provide insights into the potential visual morbidity of the myopic shift that is occurring all over the world.

This study included cross-sectional data from 15 693 persons of European descent 25 years or older from the population-based cohort studies Rotterdam Study I, II, and III, and the genetic-isolated study Erasmus Rucphen Family Study as well as the case-control Myopia Study (MYST), all of which were conducted in or near Rotterdam, the Netherlands. All participants with available data on best-corrected visual acuity and axial length or spherical equivalent were included. The rationale and study design of the studies have been described previously.21,22 A short description of each study can be found in the eMethods in the Supplement. Measurements in all studies were collected after receiving approval from the Medical Ethics Committee of the Erasmus University Medical Center, and all participants provided written informed consent in accordance with the Declaration of Helsinki.

Participants in the Rotterdam Study I, II, and III, Erasmus Rucphen Family Study, and MYST received an extensive ophthalmological examination as described previously.21 This examination included a noncycloplegic measurement of refractive error for both eyes using the Topcon RM-A2000 Auto-Refractor (Topcon Optical Company). After additional subjective refraction, best-corrected visual acuity was measured using the Lighthouse Distance Visual Acuity Test, a modified version of the Early Treatment Diabetic Retinopathy Study chart.23 Axial length was measured using the Lenstar LS900 (Laméris Ootech) for participants in the Rotterdam Study I and II or the A-scan function of the PacScan 300 AP (Sonomed Escalon) for participants in the Erasmus Rucphen Family Study and the Rotterdam Study III. Measurements of axial length were introduced in a later phase of the Rotterdam Study I, II, and III; therefore, measurements of axial length were available in 5686 study participants of these studies. Participants from MYST with an axial length greater than 30 mm underwent an A-scan.

All subsequent analyses were performed on right eyes; left eyes were used if measurements on right eyes were not available. The spherical equivalent was calculated using the standard formula, ie, adding the size of the sphere with half the size of the cylinder. In the analyses regarding spherical equivalent, persons with a history of cataract or refractive surgical procedures were excluded unless data on the spherical equivalent prior to the procedure were available. Visual impairment was defined as a best-corrected visual acuity of less than 0.3 to 0.05 or greater and blindness was defined as a best-corrected visual acuity less than 0.05, according to the World Health Organization criteria.24

We investigated the association of axial length and spherical equivalent with risk of visual impairment as well as axial length or spherical equivalent and birth year with risk of visual impairment using ordinary least squares linear regression models, with restricted cubic splines with 3 knots (10th, 50th, and 90th percentiles) for axial length and birth year and 5 knots (5th, 27.5th, 50th, 72.5th, and 95th percentiles) for spherical equivalent and birth year. In the analyses of axial length and spherical equivalent with birth year, participants from MYST were excluded because of the study design. Prevalence estimates were calculated in percentages as the number of visually impaired divided by the number in the total group multiplied by 100.

Logistic regression was used to calculate odds ratios (ORs) for visual impairment by axial length or spherical equivalent categories. We categorized axial length as less than 24 mm, 24 to less than 26 mm, 26 to less than 28 mm, 28 to less than 30 mm, and 30 mm or greater and spherical equivalent as greater than −0.5 D, −0.5 to greater than −3 D, −3 to greater than −6 D, −6 to greater than −10 D, −10 to greater than −15 D, and −15 D or less. High myopia was defined as a spherical equivalent of −6 D or less. Quadratic terms were used to test for nonlinearity of visual impairment risk. Participants were categorized as younger than 60 years or 60 years or older for analyses, which were adjusted for sex, age, and cohort. Analyses on axial length were additionally adjusted for height.25 Cumulative risk of visual impairment (ie, a visual acuity less than 0.3) was estimated by axial length and spherical equivalent categories using Kaplan-Meier product limit analysis. All participants 75 years and older were censored at 75 years to ensure unbiased estimates.

To demonstrate the potential burden of visual impairment with the increasing prevalence of myopia, we extrapolated the risk estimates from the current study to published reports on populations with high myopia.26 We considered 5 studies from Singapore,27-31 4 studies from the Republic of Korea,32-35 and 1 European consortium study4; all studies were population-based, used autorefraction or subjective refraction, and reported age-specific myopia prevalence. Prevalence by birth decade was calculated by extracting the age of participants from start year of the study. Weighted prevalence was calculated by birth decade for each region. The projected increase in prevalence of visual impairment was calculated using the reported myopia prevalence and this study’s cumulative risk of visual impairment. Ordinary least squares linear regression models were performed in R. Other statistical analyses were performed using SPSS version 21.0 (IBM). Statistical significance was set at P