This study found that riboflavin deficiency may play a role in the pathogenesis of keratoconus. Photo: Irving Martinez Navé. Click image to enlarge.

Research has yet to confirm the pathogenesis of keratoconus, a disease characterized by progressive thinning and corneal steepening. Ongoing studies are investigating the effects of various factors on its etiology, including genetic, biomechanical, proteomic, metabolic, endocrinological and environmental. Recently, researchers looked into whether metabolic substances like vitamin D, vitamin B12, riboflavin, homocysteine, folic acid and arginine might play into the development of keratoconus, confirming that every substance did either directly or indirectly.

Piggybacking off of this previous research, a team performed a study to evaluate the blood levels of homocysteine, vitamin B12, folic acid and riboflavin in patients with or without keratoconus. Among their findings, published this month in the Journal of Cataract and Refractive Surgery, was that low blood riboflavin levels in keratoconus patients are a possible risk factor in the pathogenesis of the disease.

One hundred patients with keratoconus and 200 healthy controls were included in the prospective study (age range: 18 to 35). All patients completed ophthalmologic exams and corneal tomography and gave blood samples at a single hospital eye clinic between 2019 and 2020.

The researchers found that there were no differences in levels of homocysteine, vitamin B12 or folic acid between keratoconus and non-keratoconus patients. However, riboflavin level was significantly different between the two groups (84.0µg/L in keratoconus patients and 183.6µg/L in controls). Additionally, riboflavin levels were below 180µg/L in 99% of keratoconus patients and 53.5% of controls.

“The significant decrease in riboflavin levels detected in keratoconus subjects in our study indicates that riboflavin deficiency may have a potential role in the development of keratoconus,” the researchers explained in their paper. “Riboflavin deficiency is frequently seen in the community in conjunction with other water-soluble vitamin deficiencies. The fact that vitamin B12 and folic acid levels were normal in our study makes determining the cause of isolated riboflavin deficiency difficult.”

In light of these results, the study authors stress that future studies should investigate the causes of low-endogenously synthesized riboflavin in keratoconus patients. “A longitudinal study should also be conducted to determine whether progressive keratoconus is caused by an ongoing/worsening riboflavin deficiency,” they concluded in their paper.

Sozer O, Ozalp O, Atalay E, et al. Comparison of blood levels of vitamin b12, folic acid (b9), riboflavin (b2), and homocysteine in keratoconus and healthy subjects. J Cataract Refract Surg. February 2, 2023. [Epub ahead of print].