Which are the causes of Keratoconus?

TL;DR: The exact cause of Keratoconus remains multifactorial and is not fully understood, but it is widely considered a complex interplay between genetic predisposition, environmental stressors, and biomechanical weakness of the corneal tissue. While researchers have identified several susceptibility genes, the development of Keratoconus typically requires a combination of inherited vulnerability and external triggers like chronic eye rubbing.

What are the primary causes of Keratoconus?

In medical research, we distinguish between "causes" (the fundamental mechanisms that lead to a disease) and "risk factors" (elements that increase the likelihood of developing it). In Keratoconus, the fundamental mechanism is the progressive thinning and cone-shaped bulging of the cornea. This happens because the collagen fibers that provide the cornea with its structural strength become disorganized and weakened. Think of the cornea like a fabric: in a healthy eye, the threads are woven tightly and uniformly; in Keratoconus, the weaving becomes loose and irregular, causing the tissue to lose its shape under the normal pressure of the eye.

Is Keratoconus hereditary?

Genetics play a significant role in Keratoconus, though it does not follow a simple Mendelian inheritance pattern (where one gene guarantees the disease). Approximately 10% to 15% of individuals with Keratoconus have a family history of the condition. Researchers have identified mutations in several genes, such as VSX1, SOD1, and MIR184, which may contribute to the weakening of the cornea. However, many people with these genetic markers never develop the disease, suggesting that "genetics loads the gun, but the environment pulls the trigger."

What environmental and behavioral factors contribute to the disease?

Environmental triggers are crucial in the progression of Keratoconus. The most significant, clinically recognized factor is chronic eye rubbing. Mechanical trauma to the cornea from vigorous rubbing can trigger an inflammatory response, releasing enzymes that further degrade the collagen structure. Other risk factors include:

• Atopic conditions: High rates of asthma, eczema, and severe seasonal allergies are found in patients with Keratoconus, likely because these conditions cause chronic eye irritation and subsequent rubbing.


• Oxidative stress: The corneal tissue in patients often shows an imbalance in antioxidants, making the tissue more susceptible to damage from free radicals.


• Down Syndrome and Connective Tissue Disorders: There is a statistically higher prevalence of Keratoconus in populations with conditions like Down syndrome, Ehlers-Danlos syndrome, and Leber congenital amaurosis.

What does current research tell us about the etiology?

Current research is moving toward a "two-hit hypothesis" for Keratoconus. The first "hit" is a genetic predisposition that leaves the cornea inherently weaker. The second "hit" is an external environmental factor—such as chronic mechanical rubbing or intense ultraviolet light exposure—that overwhelms the cornea’s limited ability to repair itself. Scientists are currently using advanced imaging, such as corneal topography and genetic sequencing, to better understand why some individuals with genetic markers remain stable while others progress to severe stages of Keratoconus.

Next steps

• Schedule a comprehensive eye exam with a corneal specialist to monitor your corneal thickness and topography.


• Avoid rubbing your eyes; if you suffer from allergies, consult an allergist to manage symptoms that lead to itching.


• Join the DiseaseMaps.org community of 724 members to share experiences and learn how others manage their condition.


• Discuss with your ophthalmologist whether corneal cross-linking (CXL) is a viable option to stop the progression of the disease.

Medical disclaimer: This information is for educational purposes only and does not constitute medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition.

References

• National Eye Institute (NEI): Facts About Keratoconus.


• NIH Genetic and Rare Diseases Information Center (GARD): Keratoconus overview.


• Orphanet: Rare diseases database, entry for Keratoconus.


• OMIM (Online Mendelian Inheritance in Man): Clinical synopsis for Keratoconus.