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Beyond The Cornea: The Complex Interplay of Genetics and Environment in Keratoconus

by | Sep 1, 2023 | Manuscripts | 0 comments

Chingkheinganbi Khundongbam B.Optom

M.Optom Student, Sushant University, Haryana, India

 

Roshni Sengupta, M.Optom

Assistant Professor and PhD Scholar, Sushant University, Haryana, India

 

Introduction

Keratoconus is a condition in which the cornea thins and bulges forward, resulting in myopia, irregular astigmatism, and visual impairment. It affects all ethnic groups and both sexualities globally. (1, 2)

Keratoconus pathogenesis is influenced by both hereditary and environmental factors. As the condition advances, the patient experiences visual distortion, vision loss, decreased visual acuity, and increased sensitivity to light and glare. (1, 3) In many cases, keratoconus cannot be easily corrected with glasses or soft contact lenses, so a surgical procedure such as corneal collagen cross-linking, intracorneal ring implantation, or keratoplasty will be required to stop the progression of the disease and help prevent the condition from worsening.

Keratoconus was shown to be more widespread in urban than rural environments, with a global frequency of 1.38 per 1000 people. Prevalence ranged from 0.0003% in Russia to 2.3% in the Maharashtra area of central India, perhaps due to their population’s high UV exposure. (2, 4) Men’s keratoconus ratios deteriorated faster than women’s. (5) The frequency of disease in the general population varies significantly around the globe. Moreover, keratoconus is one of the primary causes of corneal vision impairment and blindness among schoolchildren and adolescents in high-prevalence countries. (3)

How Does the Environment Shape Keratoconus Risk and Progression?

Keratoconus is caused by a complex mix of environmental and genetic factors. Eye rubbing, atopy, and UV exposure are all environmental variables. Excessive levels of any of the components induce oxidative damage to keratoconus corneas due to the inability of keratoconus to handle reactive oxygen species, resulting in a degradation process that results in corneal thinning and vision loss (as shown in Figure 1). (6) Individuals with chronic eye rubbing, particularly keratoconus patients, may accelerate disease development by maintaining consistently increased levels of protease, inflammatory mediators, and protease activity. It also causes acute inflammatory cell infiltration, the production of inflammatory chemicals and matrix metalloproteinases in the tear film, epithelial thinning, keratocyte apoptosis, a decrease in tear film break-up time, and keratometry reading alterations. (7) Excessive sun exposure may trigger oxidative damage to keratoconus corneas.

Figure 1: Keratoconus Pathogenesis

[Source: Nicolas BLOMME, S. C. (2020, March 26). Eye rubbing: A sine qua non for keratoconus? D gatinel. Int K Kerat ECT Cor Dis, 2016 5 (1):6-12. Docteur Damien Gatinel. https://www.gatinel.com/2016/07/eye-rubbing-a-sine-qua-non-for-keratoconus/]

How Genetics Predispose Us to Keratoconus?

Keratoconus pathogenesis is heavily influenced by genetics. Some of the origins of genetics include familial inheritance, discordance between dizygotic twins, and other recognized genetic abnormalities. (8)

In keratoconus-affected corneas, a buildup of cytotoxic byproducts breaks mitochondrial DNA and causes high levels of oxidative stress. The involvement of VSX1 (visual system homeobox 1) and SOD1 (superoxide dismutase 1) in the development of keratoconus is influenced by genetic variables. The most prevalent family keratoconus pattern is autosomal dominant and sporadic. (5, 6) Additional genes implicated in the development and progression of keratoconus include COL6AI, COL8AI, MMP9, and MMP2, however, they are not considered causal. In recent research, some genes linked with keratoconus may lead to other ocular syndromes (as shown in Figure 2). Down syndrome, Leber congenital amaurosis, and connective tissue abnormalities are some of the syndromes linked with keratoconus.

Figure 2: Keratoconus genes and their involvement in other ocular diseases

[Source:  YS; B. Y. B. (n.d.-a). Genetics in keratoconus: Where are we? Eye and vision (London, England). https://pubmed.ncbi.nlm.nih.gov/27350955/]

Conclusion

Keratoconus is a multifactorial common corneal ectasia and corneal condition that begins with adolescence and affects both genders as well as all ethnic groups worldwide. Both environmental and genetic factors contribute to the pathogenesis of keratoconus, with eye rubbing being the most important risk factor, followed by allergies and sun exposure. Modern genetic tools, like genome sequencing and genome-wide association technologies, have pushed researchers to learn more about the pathophysiology of keratoconus. This will demonstrate the creation of enhanced early diagnoses, treatments, and possibly prognoses in the future.

 

References:

  1. Debourdeau E, Planells G, Chamard C, Touboul D, Villain M, Demoly P, et al. New Keratoconus Risk Factors: A cross-sectional case—control study. Journal of Ophthalmology. 2022; 2022:1 –9.
  2. Omer K. Epidemiology of Keratoconus Worldwide. The Open Ophthalmology Journal. 2018; 12(1):289–99.
  3. Almusawi LA, Hamied FM. Risk factors for the development of keratoconus: A matched pair case-control study. Clinical Ophthalmology. 2021; Volume 15:3473–9.
  4. Gordon-Shaag A, Millodot M, Shneor E. The epidemiology and etiology of keratoconus. International Journal of Keratoconus and Ectatic Corneal Diseases. 2012; 1(1):7–15.
  5. Hashemi H, Heydarian S, Hooshmand E, Saatchi M, Yekta A, Aghamirsalim M, et al. The prevalence and risk factors for keratoconus: A systematic review and meta-analysis. Cornea. 2019; 39(2):263–70.
  6. Gordon-Shaag A, Millodot M, Shneor E, Liu Y. The genetic and environmental factors for Keratoconus. BioMed Research International. 2015; 2015: 1–19.
  7. Crawford AZ, Zhang J, Gokul A, McGhee CNJ, Ormonde SE. The enigma of environmental factors in keratoconus. Asia-Pacific Journal of Ophthalmology. 2020; 9(6):549–56.
  8. M; N. D. (n.d.). The genetics of keratoconus. Middle East African journal of ophthalmology. https://pubmed.ncbi.nlm.nih.gov/21572727/

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