Is Glaucoma in Your Genes? Find out with Dr. Anthony Khawaja

Understanding Glaucoma Genetics: Why Your DNA Matters More Than You Think

Glaucoma has long been recognized as a condition that runs in families, but until recently the scientific community lacked the tools to quantify that inherited risk with any precision. In this webinar, Dr. Anthony Khawaja — a clinician-scientist at the UCL Institute of Ophthalmology and Moorfields Eye Hospital in London, with fellowship training at Cambridge and Harvard — walks patients through what modern glaucoma genetics research has uncovered, what a polygenic risk score actually means, and how lifestyle factors interact with your genetic profile to raise or lower your intraocular pressure.

Glaucoma Is One of the Most Genetic Common Diseases

Dr. Khawaja opens by framing glaucoma as a disease of the optic nerve head, where elevated intraocular pressure puts biomechanical stress on nerve fibers. He explains that even so-called normal-tension glaucoma is driven by pressure dynamics. What many patients do not realize is that when researchers rank common human diseases by how much genetics contributes to who gets them, glaucoma consistently lands near the top of the list. Unlike single-gene conditions such as cystic fibrosis or BRCA-related breast cancer, glaucoma is a complex disease: hundreds of common genetic variants each nudge risk by a small amount, and it is the cumulative burden of those variants — combined with environmental exposures — that determines whether a given individual develops the condition.

From Nine Loci to Hundreds: The Role of Genome-Wide Association Studies

Dr. Khawaja traces the rapid progress of glaucoma genetics research through genome-wide association studies (GWAS). In 2016, the best available meta-analysis had identified just nine regions of the genetic code associated with glaucoma — a groundbreaking result at the time, but not nearly enough to build a useful prediction model. The real breakthrough came from the UK Biobank, a study of roughly half a million participants in the United Kingdom who provided genetic data along with detailed health measurements. For the last approximately 100,000 enrollees, the study also captured eye-specific measurements including intraocular pressure and OCT scans. With that scale, the number of confirmed genetic loci jumped to well over one hundred. More recent analyses — including work with Google on AI-based grading of optic nerve images — have pushed the Manhattan plot, the standard visualization of GWAS results, into territory that Dr. Khawaja describes as showing an unprecedented density of signals.

What Is a Polygenic Risk Score and How Accurate Is It?

A polygenic risk score (PRS) distills all of those hundreds of genetic signals into a single number that represents an individual's inherited predisposition to glaucoma. Dr. Khawaja explains that the best published PRS for glaucoma, using only genetic data plus age and sex, achieves roughly 76 percent accuracy on a receiver operating characteristic curve, with newer unpublished versions approaching 83 percent. When patients are divided into deciles by their PRS, those in the top ten percent face approximately fifteen times the risk of glaucoma compared with those in the bottom ten percent — and the latest scores are showing separation as high as 200-fold. Importantly, a high PRS does not diagnose glaucoma; it identifies who should be screened earlier and monitored more frequently, potentially years before any clinical signs appear.

Genetic Testing for Glaucoma Is Available Now

Dr. Khawaja notes that 23andMe now offers a glaucoma polygenic risk score as part of its direct-to-consumer genetic testing platform — a development he had hoped for since the early days of his research. For a clinically validated PRS, he points to a company whose test is ordered through a physician and produces two reports: one for the clinician and one written in accessible language for the patient. Ashley Felloney, who hosts the webinar on behalf of MyEyes, confirms that MyEyes plans to help patients and their family members access the validated PRS test, connecting them with the ordering process and supporting them in understanding their results alongside intraocular pressure monitoring data from the iCare HOME2 device.

Family History of Glaucoma: When Should Relatives Get Screened?

A recurring question from the audience is how early family members should begin eye exams. Dr. Khawaja advises starting about ten years before the youngest age at which a relative was diagnosed, and returning annually once you reach 40 — especially if you have a first-degree family member with glaucoma or if your polygenic risk score comes back elevated. He stresses that glaucoma in its early stages produces no noticeable symptoms, so waiting until vision loss is apparent means the disease has already progressed significantly. A high PRS can serve as the objective nudge that motivates at-risk relatives to schedule and keep those annual dilated exams.

How Caffeine, Alcohol, and Lifestyle Interact with Genetic Risk

One of the webinar's most striking findings comes from the Modifiable Risk Factors for Glaucoma Collaboration, a group Dr. Khawaja co-leads. Using detailed dietary data from UK Biobank participants, the team calculated total caffeine consumption across 19 foods and beverages — not just coffee and tea. They found a gene-environment interaction: higher caffeine intake was associated with elevated intraocular pressure, but only among individuals who already carried high genetic risk. The proposed mechanism is that caffeine stimulates additional aqueous humor production; if your drainage anatomy is genetically robust, the extra fluid drains harmlessly, but if your outflow pathways are compromised by genetic variants, your eye cannot compensate and pressure rises. A similar pattern emerged for alcohol consumption. Dr. Khawaja emphasizes that he does not advise every glaucoma patient to cut caffeine — only those whose disease is progressing despite optimal treatment. For patients with access to home intraocular pressure monitoring through a device like the iCare HOME2, he recommends measuring pressure before and at intervals after consuming caffeine to see whether their own eyes respond.

The Drainage Pathway Discovery: Schlemm's Canal Over Trabecular Meshwork

Another significant finding from the large-scale genetic data is that the primary site of outflow obstruction in many glaucoma patients is Schlemm's canal and the collector channels rather than the trabecular meshwork, which had been the conventional assumption for decades. This distinction matters for treatment selection. Procedures such as selective laser trabeculoplasty (SLT), iStent, and trabeculotomy target the trabecular meshwork; if the true bottleneck lies downstream at Schlemm's canal, those interventions may be less effective. Dr. Khawaja's group at Moorfields has developed a genetic risk score specific to the Schlemm's canal pathway, and early results presented at the ARVO conference show that patients with a high Schlemm's canal score are more likely to experience earlier failure after laser treatment. This line of research points toward a future where genetic testing for glaucoma helps guide not just screening, but the choice between drops, laser, minimally invasive glaucoma surgery, and traditional filtration surgery.

Looking Ahead: Population-Scale Genetic Screening

Dr. Khawaja closes with a vision for how genetics will reshape glaucoma care at the population level. Countries like Iceland and Finland have already genotyped large fractions of their populations. The UK's Our Future Health study aims to collect genetic data on five million adults and is already halfway to that goal. Once health systems hold that data, they can invite individuals at highest genetic risk for targeted glaucoma screening — an approach that dramatically improves the efficiency of screening programs and reduces false positives and unnecessary referrals. For patients today, the actionable takeaway is straightforward: if glaucoma runs in your family, consider a polygenic risk score to quantify your inherited risk, and pair that knowledge with regular intraocular pressure monitoring so that any changes are caught early, long before irreversible nerve damage occurs.