Myopia, Axial Length, and Age-Related Cataract: The Singapore Malay Eye Study

Abstract

Purpose.: To describe the associations of myopia and axial length (AL) with age-related cataract in an Asian population in Singapore.

Methods.: A population-based cross-sectional study that examined 3280 (78.7% response) adults of Malay ethnicity aged 40 to 80 years. Refractive error was determined by subjective refraction and AL was measured using the Zeiss IOL-Master. Digital slit lamp and retroillumination lens photographs were taken and graded for age-related nuclear, cortical, and posterior subcapsular (PSC) cataract following the Wisconsin system.

Results.: After excluding eyes with prior refractive or cataract surgery, 5474 eyes with gradable lens photographs were analyzed. In multivariate analyses adjusting for age, sex, body mass index, systolic blood pressure, glycosylated hemoglobin, smoking status, and education, myopia (spherical equivalent less than −0.5 diopter [D]) was associated with an increased prevalence of nuclear (OR: 4.99, 95% CI: 3.72–6.69) and PSC cataract (OR: 1.34, 95% CI: 1.30–1.39) but not with cortical cataract (OR: 0.85, 95% CI: 0.68–1.08) compared with emmetropia. Per-millimeter increase in AL was not associated with any of the three cataract subtypes. When myopia was defined as spherical equivalent of less than −5.0 D to −6.0 D, the OR of myopia for PSC cataract increased dramatically.

Conclusions.: Our study shows that myopia, but not AL, was associated with nuclear cataract, supporting the concept of index myopia with aging. Myopia, especially high myopia, may predispose to PSC cataract formation. Clinically, ophthalmologists should be aware that risk of PSC cataract appears to vary by refractive status.

Introduction

Age-related cataract is a leading cause of visual impairment in both the developing and developed world. ^1–8 With longer life expectancies and an aging population, the burden and impact of age-related cataract are expected to increase. Therefore, understanding risk factors and mechanisms for cataract is important to allow further research to enable the eventual prevention of this eye condition. It has been well documented in population-based studies that cataract, especially nuclear cataract, may lead to a myopic shift in refraction in the elderly. However, it is unclear whether myopia predisposes to cataract formation or the other way around. In the Visual Impairment Project, myopia was related to the development of cortical cataract, ⁹ whereas this association was not observed in other population-based cohort studies. ^10,11 It was also reported that early-onset myopia (defined as self-reported history of distance spectacle use before the age of 20 years) was related to posterior subcapsular (PSC) cataract, ^12,13 whereas nonsignificant association was found between baseline refraction and incident PSC cataract. ^10,11 Even if myopia is a risk factor for certain subtypes of cataract, it is unclear if a threshold effect exists. 

In addition, the relationship between axial length (AL) and cataract is less well studied. In the Tanjong Pagar Study, ¹⁴ no correlation was found between any cataract subtype and AL. However, Kubo et al. ¹⁵ reported that an increased severity of nuclear cataract was associated with a longer AL, whereas Lin et al. ¹⁶ suggested that a longer AL was a risk factor for progression of lenticular opacity. Studies with data of AL provide further insights into the underlying mechanisms of the relationship of myopia with cataract. 

Our study aimed to describe the associations of myopia and AL with age-related cataract, and to specifically determine if there is a threshold effect of the impact of refraction on age-related cataract in a population-based study of Malays aged 40 to 80 years. 

Methods

Study Population

The Singapore Malay Eye Study (SiMES) was a population-based, cross-sectional study of 3280 Malay adults, aged between 40 and 80 years, living in Singapore. Details of the SiMES study design, sampling plan, and methodology have been reported elsewhere. ¹⁷ In brief, the sampling frame consisted of all Malays aged 40 to 80 years living in 15 residential districts across the southwestern part of Singapore. From an initial list of 16,069 Malay names provided by the Ministry of Home Affairs, an age-stratified random sampling procedure was used to select 5600 names (1400 people from each decade of 40–49, 50–59, 60–69, and 70–80 years). Of the 5600 names initially identified, 4168 participants (74.4%) were determined to be eligible to participate. Of these, 3280 (78.7%) were examined in the clinic and the remaining 888 (21.3%) were classified as nonparticipants. There was no difference in sex (P = 0.82) between participants and nonparticipants. However, participants were younger compared with nonparticipants (P < 0.001) 

The study adhered to the Declaration of Helsinki and ethics approval was obtained from the Singapore Eye Research Institute Institutional Review Board. Written informed consent was obtained from all subjects before enrollment. 

Measurement of Myopia and Axial Length

An initial estimate of the refraction (sphere, cylinder, and axis) was measured using an autorefractor (Canon RK-5 Auto Ref-Keratometer; Canon, Inc., Ltd., Tokyo, Japan). ¹⁸ Refraction was determined by subjective refraction by trained and certified study optometrists. Autorefraction readings were used as the starting point, and refinement of sphere, cylinder, and axis was performed until the best-corrected visual acuity was obtained. Refractive error was expressed as spherical equivalent (SE). Emmetropia was defined as −0.5 diopter (D) ≤ SE ≤ +0.5 D. Hyperopia was defined as SE greater than +0.5 D. Myopia was defined as SE less than −0.5 D. 

A noncontact partial coherence laser interferometry (IOLMaster V3.01; Carl Zeiss Meditec AG, Jena, Germany) was used to measure AL. 

Grading of Cataract and Lens Opacities

Cataract was assessed from grading of digital lens photographs as previously described. ¹⁹ A digital slit-lamp camera (Topcon model DC-1 with FD-21 flash attachment; Topcon, Tokyo, Japan) and a Scheimpflug retroillumination camera (Nidek EAS-1000; Nidek, Aichi, Japan) were used to photograph the lens through the dilated pupil for assessment of nuclear, cortical, and posterior subcapsular cataract according to the Wisconsin Cataract Grading System. ²⁰ The slit beam was adjusted to completely fill the pupil, bisecting the lens from the 12 to 6 o'clock position at a 45° angle. Focus was placed on the sulcus of the lens, if visible, to allow for the grading of the presence and extent of a central optically clear zone. If the sulcus was not visible, focus was placed on the estimated center of the lens so that it was possible to grade the degree of nuclear opalescence in comparison with standard photographs. In addition, using a diffused light source, the slit-lamp camera was used to photograph the anterior segment of the lens with the focus on the iris margin. All photographs captured by the Topcon slit-lamp camera were in color. If an eye was aphakic or pseudophakic, only the anterior segment image was taken. Black-and-white Scheimpflug retroillumination photographs were then taken of each eye for grading of cortical and posterior subcapsular opacities. ²⁰  

For cataract, a five-point scale was used to assess the presence and severity of nuclear cataract. This was determined by comparing participant photographs with four standards of nuclear photographs with increasing opacity. Nuclear cataract was defined as nuclear opacity worse than Standard number 3 of the Wisconsin Cataract Grading System. ²⁰ The presence and severity of cortical cataract and PSC were graded using a circular grid divided into eight equal wedges and a central circle. The grader estimated the percentage area in each of the nine segments involved by opacities. These percentages were then summated to give an overall percentage of the whole lens area that was involved by cataract. Cortical cataract was considered present when at least 5% of the lens area was involved, and PSC was defined if any was present. 

Interview and Other Measurements

Participants underwent a standardized interview, systemic examination, and laboratory investigations. A detailed interviewer-administrated questionnaire was used to collect information about medical history, education level, and lifestyle factors. Height was measured in centimeters using a wall-mounted measuring tape and weight was measured in kilograms using a digital scale (SECA, model 782 2321009; Vogel and Halke, Hamburg, Germany). Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters squared (kg/m²). Blood pressure was taken with the participant seated and after 5 minutes of rest. Systolic and diastolic blood pressures were measured with a digital automatic blood pressure monitor (Dinamap model Pro Series DP110X-RW, 100V2; GE Medical Systems Information Technologies, Inc., Milwaukee, WI) by following methods used in the Multi-Ethnic Study of Atherosclerosis. ²¹ A 40-mL sample of venous blood (nonfasted) was collected to determine the level of glycosylated hemoglobin (HbA1c). 

Statistical Analysis

We analyzed eye-specific data using generalized estimating equation (GEE) models to account for correlation between two eyes. ²² Eyes with previous refractive or cataract surgery were excluded from analyses. Multivariable-adjusted models were fitted adjusting for potential confounders, including age, sex, BMI, systolic blood pressure, HbA1c, smoking, and education level. An age-stratified analysis was performed to investigate the association of myopia with age-related cataract in those aged less and no less than 70 years, respectively. The potential threshold effect was determined by the magnitude of odds ratios (ORs) using a different cutoff value for myopia. A P value of less than 0.05 was considered statistically significant. Statistical analyses were performed using standard statistical software (Statistical Package for Social Sciences, SPSS V16; SPSS, Inc., Chicago, IL). 

Results

After excluding the eyes with prior refractive and cataract surgery, 5474 eyes with gradable lens photographs were included in the analysis related to myopia. Table 1 shows the associations of myopia with the cataract subtypes (nuclear, cortical, and PSC) in the GEE models. Compared with emmetropic eyes, myopic eyes were associated with an increased prevalence of nuclear (OR: 4.99, 95% confidence interval [CI]: 3.72–6.69) and PSC cataract (OR: 1.34, 95% CI: 1.30–1.39), but not with cortical cataract (OR: 0.85, 95% CI: 0.68–1.08). As SE decreased (i.e., increasing myopia), there was an increased trend of nuclear (P < 0.001) and PSC cataract (P < 0.001). In multivariable-adjusted analyses, a longer AL was not associated with any of the cataract subtypes, namely nuclear (OR: 1.01, 95% CI: 0.86–1.18, P = 0.93), cortical (OR: 0.91, 95% CI: 0.81–1.01, P = 0.08), and PSC cataract (OR: 1.09, 95% CI: 0.96–1.25, P = 0.18). 

Table 1. 

 

Association of Any Nuclear, Cortical, or PSC Cataract With Myopia

Refractive Errors		Any Nuclear Cataract			Any Cortical Cataract			Any PSC Cataract
		n (%)	Multivariate* OR (95% CI)		n (%)	Multivariate* OR (95% CI)		n (%)	Multivariate* OR (95% CI)
Hyperopia, SE > +0.5 D	1997	256 (12.8)	0.55 (0.42–0.72)	<0.001	665 (33.3)	1.25 (1.04–1.52)	0.02	193 (9.7)	0.66 (0.50–0.85)	0.001
Emmetropia, −0.5 D ≤ SE ≤ +0.5 D	2065	253 (10.3)	1.00		445 (21.5)	1.00		202 (9.8)	1.00
Myopia, SE < −0.5 D	1412	442 (31.3)	4.99 (3.72–6.69)	<0.001	288 (20.4)	0.85 (0.68–1.08)	0.18	192 (13.6)	1.35 (1.02–1.78)	0.04
SE, per diopter decrease	5474	951 (17.4)	1.39 (1.31–1.48)	<0.001	1398 (25.5)	0.96 (0.91–1.01)	0.07	587 (10.7)	1.14 (1.08–1.20)	<0.001
Axial length, per mm increase	5261	802 (14.9)	1.01 (0.86–1.18)	0.93	1226 (23.4)	0.91 (0.81–1.01)	0.08	415 (8.0)	1.09 (0.96–1.25)	0.18

*  Adjusted for age, sex, BMI, systolic blood pressure, HbA1c, smoking history, and education level in GEE models.

Considering that myopic shift associated with nuclear cataract usually occurs after the age of 70 years, we performed an age-stratified analysis in those aged less and no less than 70 years, respectively. Table 2 shows the results of an age-stratified analysis on the association of myopia with nuclear, cortical, or PSC cataract. The associations of myopia with nuclear, cortical or PSC cataract in adults older than 70 years were similar compared with their counterparts younger than 70 years. Per diopter decrease in SE was associated with an increase in nuclear cataract in adults aged both older than 70 years (OR: 1.71, 95% CI: 1.46–2.02, P < 0.001) and younger than 70 years (OR: 1.41, 95% CI: 1.31–1.52, P < 0.001). The mean ages of nuclear cataract cases in persons with and without myopia were 70.3 and 71.1 years, respectively (P = 0.23). 

Table 2. 

 

Age-Stratified Analysis on the Association of Myopia With Nuclear, Cortical, or PSC Cataract

	Age, y	Myopia (SE < −0.5 D) Versus Emmetropia (−0.5 D ≤ SE ≤ +0.5 D)			Per D Decrease in SE
		Multivariate* OR	95% CI	P Value	Multivariate* OR	95% CI	P Value
Eyes with nuclear cataract	<70	4.73	3.21–6.97	<0.001	1.41	1.31–1.52	<0.001
	≥70	4.60	2.82–7.52	<0.001	1.71	1.46–2.02	<0.001
Eyes with cortical cataract	<70	0.88	0.65–1.18	0.39	0.87	0.80–0.96	0.004
	≥70	0.88	0.58–1.33	0.55	0.94	0.86–1.04	0.22
Eyes with PSC cataract	<70	1.11	0.71–1.71	0.65	1.12	1.05–1.20	0.001
	≥70	1.04	0.65–1.66	0.89	1.08	0.98–1.20	0.12

 Values in bold show the difference in ORs between adults aged less and no less than 70 years.

*  Adjusted for age, sex, BMI, systolic blood pressure, HbA1c, smoking history, and education level in GEE models.

Table 3 demonstrates the ORs of myopia for PSC and nuclear cataract using a different cutoff value for myopia. When myopia was defined as SE of less than −0.5 D to −4.5 D, the magnitude of OR did not vary significantly (lowest OR: 1.67, highest OR: 2.70). When myopia was defined as SE of less than −5.0 D to −6.0 D, the OR of myopia for PSC cataract increase dramatically (OR: 2.75 for −5.0 D; OR: 3.20 for −5.5 D; OR: 3.71 for −6.0 D). The severity of myopia was associated with an increasing trend of PSC cataract (P for trend = 0.02). The association between nuclear cataract and myopia did not increase with increasing myopia cutoffs. 

Table 3. 

 

Associations of Myopia With PSC and Nuclear Cataract Using Different Cutoff Value for Myopia

	PSC Cataract			Nuclear Cataract
	No. Eyes With PSC Cataract in Myopic Eyes	OR*	95% CI	No. Eyes With Nuclear Cataract in Myopic Eyes	OR*	95% CI
Cutoff value for myopia, D
−0.5	192	1.67	1.31–2.14	442	6.95	5.30–9.13
−1.0	151	1.78	1.36–2.34	341	7.14	5.30–9.62
−1.5	123	1.97	1.46–2.65	272	7.70	5.57–10.65
−2.0	105	2.28	1.64–3.16	209	6.99	4.93–9.93
−2.5	86	2.53	1.76–3.63	168	7.87	5.53–11.20
−3.0	60	2.05	1.35–3.12	122	6.75	4.60–9.88
−3.5	51	2.18	1.38–3.44	96	5.74	3.79–8.70
−4.0	42	2.39	1.44–3.96	76	5.51	3.50–8.69
−4.5	38	2.70	1.55–4.70	62	5.32	3.16–8.94
−5.0	32	2.75	1.51–4.99	52	4.71	2.64–8.41
−5.5	29	3.20	1.76–5.84	40	4.25	2.26–8.03
−6.0	25	3.71	1.95–7.07	31	4.00	1.97–8.12
Severity of myopia, D
−0.5 to −2.0	87	1.25	0.92–1.70	233	5.52	4.00–7.62
−2.01 to −5.0	73	2.18	1.52–3.13	157	10.44	7.04–15.48
< −5.0	32	3.01	1.66–5.45	52	7.78	4.25–14.25

*  Comparing myopic eyes versus nonmyopic eyes adjusting for age, sex, BMI, systolic blood pressure, HbA1c, smoking history, and education level in GEE models.

Discussion

Our study provides new population-based data on the associations of myopia and AL with age-related cataract in ethnic Malay persons. We found that myopic refraction was associated with an increased prevalence of both nuclear and PSC cataracts while AL was not associated with any cataract subtypes. The cross-sectional association of myopia with nuclear cataract is most likely to be explained by lens refraction rather than AL. A threshold effect may exist for PSC cataract; that is, the risk of PSC cataract may increase dramatically when refraction is less than −5.0 D. 

The SiMES confirmed the cross-sectional association between myopia and nuclear cataract reported in previous studies. ^12,23–26 This cross-sectional association can mainly be explained by myopic shift in refraction in eyes with nuclear cataract. Because myopic shift associated with nuclear cataract usually occurs after the age of 70 years, ²⁷ it is possible that myopia could also promote the early onset and development of nuclear cataract, as this association was also observed in adults younger than 70 years in SiMES. In addition, our study showed that the mean ages of nuclear cataract cases in persons with and without myopia were 70.3 and 71.1 years, respectively. This appears to suggest that myopia does not lead to a much earlier onset of nuclear cataract, and even if myopia affects nuclear cataract development, the effect would be very weak. On the other hand, nuclear cataract is well-known to be a risk factor for myopia. The Blue Mountains Eye Study reported a hyperopic shift in persons younger than 65 years and a myopic shift thereafter, and this myopic refractive change was strongly associated with baseline nuclear cataract at both 5 and 10 years. ^28,29 The Beaver Dam Eye Study also reported similar trends ^30,31 and found that persons with greater severity of nuclear sclerosis at baseline tended to have myopic changes as well. 

Previous studies have also demonstrated a clear cross-sectional association of myopia with PSC cataract. ^12,14 The Tanjong Pagar Survey reported that PSC cataract was related to myopia, as well as a deeper anterior chamber, thinner lens, and longer vitreous chamber. ¹⁴ The Blue Mountains Eye Study reported a weak association between myopia and nuclear cataract, but a strong association between myopia and PSC cataract, especially in eyes with early-onset myopia (defined as having a history of wearing spectacles for distance before the age of 20 years). ¹² Our SiMES study indicated that the prevalence of PSC cataract increased dramatically when myopia was defined as less than −5.0 D. We think that myopia, especially high myopia, might lead to PSC cataract. The insignificant associations observed in previous cohort studies may be due to a small number of cases, short follow-up period, or inaccurate estimation due to cataract surgery between study visits. PSC cataract affects vision more severely and thus leads to surgery sooner than other types of cataract. 

Previous studies on the relationship between myopia and cortical cataract have reported conflicting trends. The Tanjong Pagar Survey reported no association between myopia and cortical cataract, ^12,14 whereas the Blue Mountains Eye Study demonstrated that high myopia was associated with cortical cataract. ¹² The Beaver Dam Eye Study reported that incident cortical cataract was associated with hyperopia. ¹¹ Our study found no association of myopia with cortical cataract. 

Whether AL is associated with aged-related cataract remains unclear. Kubo et al. ¹⁵ reported that an increased severity of nuclear cataract was associated with a longer AL, whereas Lin et al. ¹⁶ suggested that a longer AL was a risk factor for lenticular progressive myopia. A possible hypothesis is that a decreased diffusion of nutrients to the lens occurs due to a longer vitreous cavity. ¹⁵ The Tanjong Pagar Study reported no correlation between any cataract subtype and AL. ¹⁴ Our study found results similar to the Tanjong Pagar Study, where axial length was not significantly related to any cataract subtypes. It is likely that factors other than AL are related to cataract development, and previous studies that found an apparent association between the two may have been limited by small samples (198 eyes in the Kubo et al. study ¹⁵ and 47 in the Lin et al. study ¹⁶ ). 

Strengths of our study include a large sample size, high response rate, and use of standardized protocols for cataract grading. We used the GEE models with the right and left eye data combined to increase statistical power. The GEE method also affords greater precision of estimation and is less sensitive to missing data for some eyes. ³² Limitations of our study included its cross-sectional design, making it difficult to establish the temporal relationship between the factors under study. Also, participants were significantly younger than nonparticipants, thus selection bias may have occurred. Excluding an older cohort that contains relatively more cataract cases due to its older age distribution might also have caused an imprecision in the estimation of associations due to reduced number of cases. 

In conclusion, our study shows that myopia was associated with an increased prevalence of both nuclear and PSC cataract. However, the lack of associations with AL suggests that the association between myopia and nuclear cataract is explained by lens refraction rather than AL. The prevalence of PSC cataract increased dramatically when myopia is defined as SE of less than −5.0 D. Further well-designed cohort studies with a sufficient follow-up period and high follow-up rate are warranted to elucidate the longitudinal associations. 

Acknowledgments

Supported by the National Medical Research Council Grants 0796/2003, 0863/2004, and CSI/0002/2005, and Biomedical Research Council Grant No 501/1/25-5. 

Disclosure: C.-W. Pan, None; P.Y. Boey, None; C.-Y. Cheng, None; S.-M. Saw, None; W.T. Tay, None; J.J. Wang, None; A.G. Tan, None; P. Mitchell, None; T.Y. Wong, None 

Footnotes

 C-WP and PYB contributed equally to the work presented here and should therefore be considered equivalent authors.