TREATING WITH MORE PRECISION

ROIBEÁRD O’HÉINEACHÁIN REPORTS

Genomic analys is offers the prospect of personalised glaucoma management, said Ananth C Viswanathan MD, PhD, but achieving that goal will involve a gradual process involving big data and empirical outcomes.

“It is already changing our practice, and we are on a journey where it will change our practice for the benefit of our patients.”

He noted the evidence base for genotype analysis in glaucoma management is still in its early stages. A review of the literature he co-authored with Anthony P Khawaja indicated genetic testing on a population level is not currently justified.i Furthermore, the latest EGS guidelines advise against offering routine genetic testing to POAG patients.

“It might seem genomics does not have a great deal to do with glaucoma management, but evidence is rapidly accumulating that genomic information can be very helpful,” Prof Viswanathan explained.

As an example, he cited a study involving participants of the Ocular Hypertension Treatment Study (OHTS). It showed the risk allele in the TMCO1 gene (related to intraocular pressure) had a higher hazard ratio for conversion to glaucoma than any of the previously identified risk factors, including central corneal thickness, vertical cup-to-disc ratio, visual field defect, and IOP itself.ii

“The OHTS risk calculator has now been modified to take account of this. That means if you use the calculator, you are using genomic information,” he said.

Another approach uses a multi-trait analysis of glaucoma risk variants across the genome, putting them together to form a polygenic risk score (PRS). A study involving optic nerve photographs of 67,040 UK Biobank participants showed those in the top PRS decile had a 15-fold increased risk of developing advanced glaucoma compared to the bottom decile.iii

Precision Medicine

Prof Viswanathan noted genomic analysis will be a valuable tool in developing precision medicine, an approach to disease treatment and prevention that considers the variability in an individual’s genes, environment, and lifestyle.

“We are already using genomics for biomarkers to guide our management of the condition in a number of areas—all of which have a crucial role in glaucoma management.”

He explained its development as an iterative process, starting with a broad stratum of diagnostic and prognostic groups. Then, as information accumulates on how risk factors influence disease and treatment outcomes, treatment protocols gradually refine.

“It is not as if we are going to go from nothing to full precision medicine by the flick of a switch,” he observed. “It will develop gradually.”