This month I want to take a look at the incredible field of genetic testing. Two recent advances for the cornea will soon impact the way we practice in a very positive way, namely early detection. In particular, the first test will help us make a timely diagnosis for keratoconus and other corneal diseases; the second will help us identify corneal pathogens, especially when standard cultures and PCR testing fails to identify the causative organism(s).

Genetic Detectives

AvaGen (Avellino) will be the first commercially available test of its kind (Q2 2021) to help identify patients that have risk of developing keratoconus and certain other corneal dystrophies. It will be helpful to provide timely alerts to those predisposed to keratoconus. If detected, preventative strategies such as warning not to rub one’s eyes, sleeping on their back and perhaps getting collagen crosslinking early are all important to minimize morbidity. AvaGen looks at over 1,000 variants across 75 different genes for keratoconus and over 70 TGFBI mutations for corneal dystrophies.1 

Metagenomic deep sequencing (MDS) is genetic testing that simultaneously and independently detects nucleic acid fragments of any pathogen that might be present and allows ongoing pathogen discovery. MDS is currently not FDA approved and not yet in the mainstream. It’s primarily used when there is obvious infection but no known cause after standard testing. Investigators at UCSF are doing incredible work with this technology trying to streamline workflow issues, detection limits and interpretation difficulties to eventually make this routine.  It’s a promising test with some challenges including cost, differentiating pathogenic organisms causing infection from commensals and the ethical question of generating genetic data (disease causing genetic mutations). 

We’re familiar with the limitations and errors with standard cultures and the profiling required ahead of time for PCR testing. Corneal cultures—our gold standard—have a sensitivity of only about 60%. Unlike PCR testing, a targeted test where you need to ask for specific pathogen identification probes, MDS is an unbiased method for detecting pathogen(s) responsible for any corneal infection overcoming the need to separate the genomes or culturing the microbes.2,3 In other words, you don’t have to ask ahead of time to probe for any specific pathogen. Similar to any diagnostic assay, clinical diagnostic correlation and assessment of treatment response remain important.2

Data Vulnerabilities

I must digress a bit and share some potential problems of such technology when not used properly or as intended. A recent 60 Minutes presentation interviewed local Scranton star, William Evanina, director of the National Counterintelligence and Security Center. 

Throughout the interview, Bill stressed the national security risks of foreign adversaries having access to our biologic and healthcare data. Our government is primarily concerned with their ability to generate genomic data and the potential to control the United States’s healthcare and pharmacy companies. Bill suggests that those quick to offer their services for COVID testing across the United States likely showed significant interest because, apparently, our DNA is so valuable. Might they one day circumvent and do an “end-around” on our healthcare system and target citizens directly? On one hand, all of this might be good for future treatment and cures, but what else exists that might be unfavorable to our healthcare system? It’s an interesting interview to check out.

I see the field of genetic testing and nucleic acid analysis as an exciting frontier with many rewards, and at the same time with a few risks. As long as we use the data as its intended—namely to treat and eventually cure the population at risk—science advances. And if we not do not abide by that goal, the consequences are serious. Let’s hope Bill Evanina is looking at a worst-case scenario and being overly cautious in his assessment of how this data is being used and targeted for future use. 

On a more positive note, the advances mentioned above will soon help us better serve our patients from the front to the back of the eye. through genomic testing. I can’t wait to use them.

1. Genetic Testing Registry. AvaGen test for keratoconus risk factors adnd corneal dystrophies. Last updated September 16, 2020. Accessed March 15, 2021.

2. Gallon P, Parekh M, Ferrari S et al. Metagenomics in ophthalmology: hypothesis or real prospective? Biotechnol Rep. 2019;23(9):e00355.

3. Seitzman GD, Hinterwirth A, Zhing L et al.: Metagenomic deep sequencing for the diagnosis of corneal and external disease infections. Ophthamology. 2019;126(12):1724-6.