Research suggests there are nearly 500 different eye-related diseases, with more than 800 ocular and periocular manifestations of systemic disease. Hundreds of genes, if mutated, can cause disease isolated to the eye.1 Fortunately, genetic testing can aid health care providers in managing inherited diseases. Specifically, genetic testing is beneficial for (1) a confirmational diagnosis, (2) newborn screening, (3) carrier screening and (4) forensic testing.1-3

Exciting new frontiers are providing measures for pharmaco­genomics, whole genome and whole exome sequencing, and even tumor analysis.2 The latter, for example, looks at genetic alterations that drive tumor growth and the genetics that help predict therapeutic response.

Identification of susceptibility loci has helped researchers better understand the complex pathophysiology of several ocular and neurologic diseases.4

Clinical Applications
Many recent findings in eye care are a result of genetic testing, and some are applicable to therapy today:

• Though controversial, research suggests there may be a different response to the AREDS formula based on specific genotypes, and testing for the genotype for which zinc supplementation may be pro-inflammatory in patients with macular degeneration could impact therapy.

• For the cornea, genetic testing is now available to identity Avellino’s corneal dystrophy.

• The Asper Biotech test screens for 333 mutations in 13 genes for corneal dystrophy.5

• Researchers have been investigating gene therapy to improve the quality of donor tissue for corneal grafts, which might decrease the risk of graft failure and rejection.

Therapy Advances

The key is to target therapy with testing prior to gene expression. Gene augmentation—treatment for deficient genes—is easier than gene knock-out therapy (blocking a gene causing a detrimental effect).4 For example, gene augmentation therapy is now possible for Leber’s congenital amaurosis when a RPE65 deficiency is found.

Using nanoparticles as vectors for delivering DNA is an exciting advancement.4,5 For example, researchers recently used lentiviral-mediated genetic modification of cultured endothelial cells to deliver genes to the endothelium.5

Creating new viral vectors with directed evolution is the key to timely adoption. Researchers can now create viruses in the lab to maximize their diversity and can promote the evolution of viruses, through an artificial selection process, that have the traits researchers need.3

Keep Patients Informed

As helpful as genetic testing can be, it can raise both social and ethical issues, and clinicians must be careful to discuss the value and limitations of genetic testing with patients.6 When ordering tests, it is the clinician’s duty to educate patients on the likelihood that they have a particular disease, the spectrum of disease possibilities (from mild to severe), recurrence rates, chance of passing the condition to offspring, possible treatments and reproductive alternatives.5,6

The ramifications of knowing that you have the genes for a particular disease without a current treatment can be traumatic. Fortunately, patients are protected by the Genetic Nondiscrimination Act, which does not allow health care insurers or employers to discriminate based on genetic predisposition or pre-existing conditions.5

The last two decades have seen an explosion of research in genomics, with rapidly expanding genetic medicine. Gene therapy specific to the cornea and anterior segment is a particularly exciting frontier, considering corneal disease is responsible for a significant amount of blindness worldwide. Ocular gene testing and therapy research is robust with a high priority in funding and should prove fruitful in the very near future.

1. Uthra S, Kumaramanickavel G. Gene therapy in ophthalmology. Oman Ophthalmol. 2009:2(3):108-10.
2. American Medical Association. Genetic Testing. Available at Accessed December 5, 2016.
3. Bethke W. The future of gene therapy. Rev Ophthalmol. 2016:23(4):36-9.
4. Fritsche LG, Fariss RN, Stambolian D, et al. Age related macular degeneration: genetics and biology coming together. Annu Rev Genomics Hum Genet. 2014;15:151-71.
5. John T. Decoding the genetics of corneal disease. Rev Cornea Contact Lenses. 2014 June:24-8.
6. Bateman B, Silva E. AAO Task Force on Genetic Testing. Ophthalmol 2013;120(10):e72-3.