Frequency and prediction of myopic macular degeneration in adults

Paper title: Predictors of myopic macular degeneration in a 12-year longitudinal study of Singapore adults with myopia

Authors: Li Lian Foo (1,2,3), Lingqian Xu (2), Charumathi Sabanayagam (2,3), Hla M Htoon (2), Marcus Ang (1,2,3), Jingwen Zhang (4), Kyoko Ohno-Matsui (5), Ching Yu Cheng (2,3), Quan V Hoang (1,2,3,6), Chuen-Seng Tan (7), Seang-Mei Saw (2,3,7), Chee Wai Wong (1,2,3,8)

1. Singapore National Eye Centre, Singapore
2. Singapore Eye Research Institute, Singapore
3. Duke-NUS Medical School, National University of Singapore, Singapore
4. GKT School of Medicine, King's College London, London, UK
5. Ophthalmology and Visual Science, Tokyo Medical and Dental University, Bunkyo-ku, Japan
6. of Ophthalmology, Columbia University, New York, New York, USA
7. Saw Swee Hock School of Public Health, National University of Singapore, Singapore
8. Asia Pacific Eye Centre, Gleneagles Hospital, Singapore

Date: May 2022

Reference:  Foo LL, Xu L, Sabanayagam C, Htoon HM, Ang M, Zhang J, Ohno-Matsui K, Cheng CY, Hoang QV, Tan CS, Saw SM, Wong CW. Predictors of myopic macular degeneration in a 12-year longitudinal study of Singapore adults with myopia. Br J Ophthalmol. 2022 May 9: bjophthalmol-2021-321046.

[Link to abstract]

The purpose of this study was to gain insight into predictive features for myopic macular degeneration for adult myopes.

The Singapore Malay Eye Study and The Singapore Indian Eye Study recruited 828 Malay and Indian adults aged 40-80 years with spherical equivalent myopia of -0.50D or more.  Eye examinations, including axial length measurement and fundus photography, were performed at baseline and repeated over a 12yr period for comparison.

Fundus images were assessed and graded for Myopic Macular Degeneration (MMD) using the Meta-Analysis for Pathological Myopia (META-PM) classification.  The predictive factors for classification and progression of MMD were expressed as risk ratios calculated from multivariable regression modelling and a receiver operating curve (ROC) was plotted to present the predictive elements for developing MMD.

• For myopic adults without a diagnosis of MMD at baseline, 10% suffered onset within 12 years.
• For myopic adults who already had MMD at baseline,12% suffered progression within 12 years.
• Age, higher myopia and longer eye lengths were independent risks for both onset and progression of MMD.

The best predictive factor was a tessellated fundus, with a risk ratio of 2.50. In the eyes that developed MMD, 83% had tesselated fundus at baseline. The incidence of MMD was highest in those who were older (≥60 years old) with tessellated fundus (34.9%). Similarly, a higher incidence was found in those with high myopia and tessellated fundus (47.4%), independent of age.

The risk of MMD onset was also increased in those who were Malay (versus Indian) ethnicity and in females compared to males, but these were not risk factors for MMD worsening. For both MMD onset and progression, each additional 1mm of axial length and 1 year of age increased the risk of MMD development by a relative risk of just over 1. Educational level was not related to MMD risk.

Myopic macular degeneration (also known as myopic maculopathy) has serious consequences for ocular health and vision. It has been previously reported that each 1.00D increase in myopia increased the risk of myopic maculopathy by around 60%, but also that each 1.00D reduction in final myopia reduced the risk of MMD by 40%. This is discussed in more detail here.

• This study has highlighted the importance of recognising the predictive factors for MMD in adults 40-80 years, with 10-12% of ALL myopes (-0.50D or greater), not just high myopes, showing development of MMD over a decade.
• An adult myope with a tesselated fundus should be monitored closely for onset of MMD, as this is the greatest predictive factor. A tesselated fundus is defined as the visualization of large choroidal vessels at the posterior pole - read more about this here.
• Other independent predictive factors are increasing age and axial length. The relationship of axial length to MMD indicates both the benefit of tracking its measurement and the importance of applying myopia control treatments in childhood to reduce excessive growth.

1. This study did not report the percentage of adults with MMD of certain ages. Age was described as a risk factor for both MMD onset and progression, increasing with each additional year. Understanding how frequently MMD occurs in younger adults (40-60 years) could help to alert eye care practitioners to the importance of close retinal health monitoring in adult myopes.
2. The prevalence of myopia in East Asian countries is around twice that of aged-matched populations in other countries² and the overall prevalence is increasing, particularly for younger people.² European data indicates that from a lower base rate of myopia, the prevalence of myopia has increased in the past few decades and nearly half of 25-29yr olds are now myopic.^4,5  Repeating this study in Europe would provide valuable information on the incidence and prevalence of MMD in other ethnicities.

Title: Predictors of myopic macular degeneration in a 12-year longitudinal study of Singapore adults with myopia

Authors: Li Lian Foo, Lingqian Xu, Charumathi Sabanayagam, Hla M Htoon, Marcus Ang, Jingwen Zhang, Kyoko Ohno-Matsui, Ching Yu Cheng, Quan V Hoang, Chuen-Seng Tan, Seang-Mei Saw, Chee Wai Wong

Purpose: To investigate the predictive factors for myopic macular degeneration (MMD) and progression in adults with myopia.

Methods: We examined 828 Malay and Indian adults (1579 myopic eyes) with myopia (spherical equivalent (SE) ≤-0.5 dioptres) at baseline who participated in both baseline and 12-year follow-up visits of the Singapore Malay Eye Study and the Singapore Indian Eye Study. Eye examinations, including subjective refraction and axial length (AL) measurements, were performed. MMD was graded from fundus photographs following the Meta-Analysis for Pathologic Myopia classification. The predictive factors for MMD development and progression were assessed in adults without and with MMD at baseline, respectively as risk ratios (RR) using multivariable modified Poisson regression models. The receiver operating characteristic curve was used to visualise the performance of the predictive models for the development of MMD, with performance quantified by the area under the curve (AUC).

Results: The 12-year cumulative MMD incidence was 10.3% (95% CI 8.9% to 12.0%) among 1504 myopic eyes without MMD at baseline. Tessellated fundus was a major predictor of MMD (RR=2.50, p<0.001), among other factors including age, worse SE and longer AL (all p<0.001). The AUC for prediction of MMD development was found to be 0.78 (95% CI 0.76 to 0.80) for tessellated fundus and increased significantly to an AUC of 0.86 (95% CI 0.84 to 0.88) with the combination of tessellated fundus with age, race, gender and SE (p<0.001). Older age (p=0.02), worse SE (p<0.001) and longer AL (p<0.001) were found to be predictors of MMD progression.

Conclusions: In adults with myopia without MMD, tessellated fundus, age, SE and AL had good predictive value for incident MMD. In adults with MMD, 1 in 10 eyes experienced progression over the same period. Older age, more severe myopia and longer AL were independent risk factors for progression.

[Link to abstract]