Genetic testing for keratoconus facilitates earlier recognition of condition

Reviewed by Dr Sumit Garg.

Great strides have been made in recognising and treating keratoconus. Recent imaging technologies, such as optical coherence tomography, have identified thinning of corneal tissue over the cone, and wave-front aberrometry shows higher-order aberrations that may facilitate the diagnosis.

Yet the pathway to diagnosing the condition is not always free of roadblocks, according to Dr Sumit Garg, professor of cataract, corneal and refractive surgery at the Gavin Herbert Eye Institute, University of California, Irvine, California, United States. Dr Garg said that keratoconus has two components: genetic and environmental. The latter, he said, includes allergies and eye rubbing (during waking and sleeping hours), which is a huge driver of keratoconus progression. If eye rubbing persists, progression can occur despite cross-linking treatment.

Dr Garg also pointed out that the diagnosis can depend on where a patient lives and their genetic make-up. “The keratoconus prevalence is individualised and [keratoconus] can be prevalent in up to 5% of particular populations as shown in a recent study,” he said.¹ With the rapid advancements in this field, the next step is determining the role of genetic testing in this patient population.

Assessing the risk

Figure 1. Results from 32-year-old patient.

Genetic testing in patients at risk of keratoconus is in its infancy. Dr Garg reported that AvaGen75 (Avellino) is a test—the first of its kind— that looks at variants of genes reported to be associated with keratoconus. “The test, which looks at 75 genes and more than 2,000 variants, provides a scale ranging from 0 to 100 that defines the genetic risk of a patient developing keratoconus,” Dr Garg said.

The manufacturer reports that the test provides a risk score from data based on multiple gene clusters that have a high correlation with keratoconus, with the goal of providing an early diagnosis. Dr Garg emphasised that keratoconus is polygenic and not binary (i.e., the presence of genes does not necessarily mean that a patient has clinical evidence of keratoconus). He also cited a study² that found that when genetic testing is coupled with advanced imaging, the chances of identifying keratoconus early are greater.

In his practice, he is offering genetic testing as an option, especially when there is a suspicion of keratoconus. Those who request a refractive surgery and those with family members who have been diagnosed with keratoconus are also offered testing.

Representative results of genetic testing

Figure 2a. Results from 31-year-old patient.

Figure 2b. Results from 31-year-old patient. (Images courtesy of Dr Sumit Garg)

Dr Garg reported the case of a woman aged 32 years, who was referred for an ocular evaluation for a possible LASIK procedure. The patient was highly myopic with high cylinder, but her vision had been stable. The best-corrected vision was 20/20 bilaterally; she denied eye rubbing.

The topography maps indicated possible posterior changes, with some steepening in the corneal centre, and changes on the ABCD score. The Kmax values were generally thin overall. The patient had no family history of keratoconus.

Genetic testing showed moderate-to-high risk of keratoconus. The decision was made not to perform the refractive procedure and to perform a follow-up examination in 6 months. If the changes were progressive, corneal cross-linking could be considered. If follow-up showed no progression, an implantable collamer lens could be considered.

A second case was that of a woman aged 31 years, who presented after being evaluated for LASIK in another practice, where a photorefractive keratectomy was recommended. The patient, who was a mild myope with low cylinder, had no recent refractive changes and she denied eye rubbing.

The patient’s best-corrected vision was 20/20. The maps did not show any abnormality and the genetic testing was inconclusive. The patient became pregnant and any refractive considerations were postponed.

A third case was that of a man aged 27 years, who presented for a LASIK evaluation. The patient was a mild myope and previously wore contact lenses. The refraction was stable. His maps showed slight corneal thinning but a good residual stromal bed. His father had a history of keratoconus. Dr Garg said that for this patient, genetic testing is the next step and may help in the treatment plan.

“Genetic testing is new and holds a lot of promise,” Dr Garg concluded. “It helps us to risk-stratify our patients, help with clinical quandaries, and hopefully will facilitate earlier diagnosis and screening for keratoconus. It is important that the disease is not binary but rather a spectrum. Patients must understand that if they undergo genetic testing it will not determine whether they have keratoconus. Genetic testing will provide another data point to help identify keratoconus.”

Sumit Garg, MD

E: gargs@uci.edu

This article is adapted from Dr Garg’s presentation at the American Society of Cataract and Refractive Surgery’s annual meeting in Washington, D.C. He is a consultant to Avellino and Glaukos.

References

1. Torres Netto EA, Al-Otaibi WM, Hafezi NL, et al. Prevalence of keratoconus in paediatric patients in Riyadh, Saudi Arabia. Br J Ophthalmol. 2018Oct;102:1436-1441.

2. Chen S, Li XY, Jin JJ, et al. Genetic screening revealed latent keratoconus in asymptomatic individuals. Front Cell Dev Biol. 2021 May;9:650344.