Should I Have Genetic Testing for Keratoconus?

Should I Have Genetic Testing for Keratoconus?

by Brian Chou, OD, FAAO, FSLS

  • April 14, 2020 (Updated April 17, 2022)

Keratoconus has a well-established genetic link.  A 2012 review article found that between 6 to 23.5% with keratoconus have someone else in the family with it.  Furthermore, relatives of keratoconus patients are 15-67 times at higher risk to develop keratoconus compared to those with unaffected relatives.  Mutations in several different genes appear to underlie keratoconus.

Most cases of familial keratoconus are autosomal dominant, meaning that just one parent with the genetic abnormality can lead to keratoconus in the child.  However, there may be autosomal recessive keratoconus as well, where both parents must have the genetic mutation for their child to get keratoconus.

There are several external factors that might combine with genetics to bring about keratoconus.  These include eye-rubbing, atopy (allergy, asthma, and eczema), sun exposure, and geography.  The interplay of epigenetics, i.e., environmental factors on those with genetic predisposition, is still not well understood.

First commercially available genetic risk assessment for keratoconus

In February of 2020, Avellino Labs launched the AvaGen test.  It is the first and only commercial genetic test to assess risk for keratoconus.  AvaGen involves four quick and non-invasive cheek (buccal) swab samples taken at the doctor’s office.  This is not a do-it-yourself, at home kit.  Results arrive in two to four weeks.  Although it may not interest those undergoing the test for keratoconus, AvaGen also identifies the presence or absence of hereditary corneal dystrophies linked to the TGFBI gene (granular corneal dystrophy type 1 and type 2, epithelial basement membrane dystrophy, lattice corneal dystrophy, Reis-Bücklers corneal dystrophy, and Thiel-Behnke corneal dystrophy).

Due to the COVID-19 pandemic, Avellino Labs announced on March 19, 2020, they temporarily suspended production and processing of AvaGen tests to direct their resources to their SARS-CoV-2/COVID-19 test.  Since the summer of 2021, Avellino has resumed processing AvaGen testing.

AvaGen examines over 2,000 variants across 75 genes for keratoconus using whole exome DNA sequencing, a faster and more cost-effective genomic technique, which allows for discovery of rare, hard-to-find, pathogenic variants contributing to keratoconus.

Who should consider AvaGen?

The role of assessing the genetic risk for keratoconus is not yet established.  However, it will likely help:

  • Those told that they might have keratoconus.
  • Individuals with a history of keratoconus or other corneal diseases within the family.
  • Patients contemplating LASIK that wish to minimize their risk of surgical complications.

For these individuals, the results of AvaGen may help them decide if corneal cross-linking surgery is appropriate to stabilize against future progression of keratoconus, or if LASIK is a reasonable option.  LASIK causes poor outcomes for keratoconus.  AvaGen assesses risk for keratoconus using an index.  It is not like a pregnancy test where the result is either “yes” or “no”.  The test does not currently provide information on the predicted severity or rate of progression anticipated for those at risk for keratoconus.

The clinical role of AvaGen for someone already diagnosed with keratoconus is not as obvious.  To some degree, it may confirm what is already known.  Still, it could help enhance detection of keratoconus in other family members that under AvaGen testing.  From the administrative role, certain vision plans could eventually require genetic risk assessment for keratoconus to authorize coverage for medically necessary contact lenses.  Likewise, medical insurance may require this genetic test as one of the criteria for covering corneal cross-linking surgery.

How well does AvaGen work?

The jury is still out on how well AvaGen works. Early testing experience at ReVision Optometry and published in early 2022 show inconsistent results of AvaGen genetic testing for keratoconus. Avellino has acknowledged releasing an improved scoring analysis in October 2021. Please stay tuned for more reports on the promise of genetic testing for keratoconus.

How is the testing for keratoconus different from 23andMe or Ancestry?

Consumer genetic tests offered by 23andMe and Ancestry use genotyping, which looks at DNA sequences at locations known to be valuable.  These are not intended to diagnose or treat medical conditions or disease.  By comparison, AvaGen is a medical grade test using Next Generation Sequencing which can help you and your doctor decide on an appropriate medical plan.

Some authors have expressed concerns that companies like 23andMe reserve the right to use your personal information, including genome, to sell you products and services.  Genetic tests ordered by your physician have a higher standard for protecting patient confidentiality.

What is the cost?

Insurance does not presently cover the cost of genetic testing for keratoconus.  It is an out-of-pocket expense.  Expect it to cost under $400.  AvaGen can be performed during your comprehensive eye examination at ReVision Optometry.  For patients, this may bring assurance, whether for safety in undergoing LASIK or those contemplating corneal cross-linking surgery in the future.  Other patients with keratoconus have wondered about the risk of their children in developing keratoconus.  AvaGen can be done at any age and may provide a peek into the future, allowing for a more proactive and preventative treatment plan if risk is identified.  This test needs to only be done once and it also assesses for specific corneal dystrophies associated with the TGFBI gene.  For patients that exhibit genetic risk for keratoconus and those that are positive for a TGFBI corneal dystrophy, a complimentary session with a certified genetic counselor is included with the AvaGen test.


Precision medicine for keratoconus is just getting started.  The future may bring targeted pharmacologic treatments based on one’s unique genetic expression of keratoconus, and perhaps even CRISPR-based gene editing. With advanced scleral contact lens treatment to optimize vision in keratoconus, patients with keratoconus have many exciting and emerging diagnosis and treatment tools to bring them hope.  Schedule your keratoconus evaluation at ReVision Optometry to start taking control of keratoconus today.

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