Why Our Study Matters

         The article is the first one demonstrating the vision state and refraction parameters in different inherited retinal disease (IRD) subtypes and in various gene groups in Asian patients. The unique disease-causing gene in Asians may lead to different refractive state compared to patients from other regions.

Understanding Refractive Errors: Theories Behind the Development

         Refractive errors mean the light does not form image properly on the retina (the light-sensitive layer at the back of the eye), causing blurry vision. The most common types include nearsightedness (i.e., myopia), farsightedness (i.e., hyperopia), and astigmatism. Hyperopia is commonly observed in infants. As children grow, their eyes gradually lengthen and the refractive power of the cornea and lens becomes less, a process called “emmetropization”, which helps focusing accurately.¹ Hyperopia usually results from insufficient emmetropization or a high initial refractive error.² Myopia, on the other hand, develops when the axial length increases more than needed to maintain clear vision.¹ Animal studies suggest that myopia develops when images form behind the retina on the peripheral retina (known as hyperopic defocus), which is the basis for the theory behind ortho-K lenses.³

         Both genetic factors and environmental influences contribute to the development of refractive errors.⁴ Although genetic analyses show no significant difference in myopia risk between people of Asian and European ancestry,⁵ myopia is much more common in Asian countries, affecting over 80% of people, compared to around 30% in Western countries.⁶ The higher rate in Asia is thought to be related to high study pressure and less time spent outdoors.⁷ Taiwan, in particular, has one of the highest rates of myopia in the world. Owing to the National Health Insurance Research Database, a series of population-based myopia prevalence surveys has been conducted from 1983 to 2017, allowing for the assessment of the prevalence of myopia in children or adults of different ages.⁷

Inherited Retinal Disease (IRD): Exploring Possible Link to Refractive Errors

         IRD is a group of congenital eye diseases which cause the retina to gradually deteriorate, potentially leading to worsening vision or even blindness. IRD can be categorized by the primary affected cell type, including rod-dominated diseases, cone-dominated diseases, generalized retinal degeneration, and vitreoretinopathies. The same subtype of IRD can be caused by different genes, while a single gene can result in various diseases, illustrating the complex relationship of genetics and disease expression. The diverse ages of disease onset, the different types of cell it affects, and the various genes involved make IRD a nature model to explore how refractive errors develop and impact vision.

         In earlier research from the Taiwan Inherited Retinal Degeneration Project (TIP), we identified the most common disease subtypes and the genes most frequently linked to IRD in Taiwanese patients. Approximate two-thirds of the patients in the cohort were diagnosed with retinitis pigmentosa, followed by macular dystrophy, cone dystrophy/cone-rod dystrophy, Leber congenital dystrophy, and Biette’s crystalline dystrophy, among others. The genetic analysis revealed that ABCA4 variants were the most common disease-causing gene, followed by genes such as EYS, USH2A, CYP4V2, RPGR, PROM1, CRB1, PRPF31, and RDH12……etc.⁸ The regional database enables us to examine refraction parameters across different disease subtypes and genotypes.

Our Research Approach: Methods and Techniques in Action

         Overall, five hundred right eyes and four hundred and nighty four left eyes were enrolled. We compared the visual acuity and refraction parameters across different disease subtypes to assess conditions that primarily affect the macula (the central retina) and those mainly involve the peripheral retina. In addition, the rates of myopia and high myopia were examined between the general population and the four most prevalent disease subtypes to determine if patients with IRD were more or less prone to developing refractive error.

         For genotype studies, the three most prevalent genotypes identified in the TIP cohort, including ABCA4, EYS and USH2A, were used to compare to the general population regarding myopia and high myopia rates. Nine of the most common genotypes in the TIP cohort were analyzed to assess the visual acuity and refractive parameters.

Study Summary: Key Findings and Takeaways

         In our Taiwanese cohort, patients with different IRD subtypes shared similar refractive state regardless of the age of onset and related photoreceptor dysfunction, except for higher degree of astigmatism found in patients with Leber’s congenital amaurosis. The rate of myopia was also similar between patients with IRD and the general population. Regarding the association between the causative genes and refractive state, more advanced myopia was seen in RPGR and PROM1-related patients, and significantly poorer visual acuity was found in ABCA4, CRB1 and PROM1-related patients.

         With distinct myopia prevalence and varying disease-causing genotypes in Asians, our exploratory study could serve as a basis for future research on how refractive errors relate to retinal degeneration and offer as a reference for larger, international studies involving different ethnic groups.

Reference:

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