Genetic ophthalmologic disorders are among the leading causes of visual impairment. From corneal dystrophy to optic neuropathy, there are many conditions known to be genetic in nature, affecting every portion of the eye from the anterior to the posterior segment.

Taken separately, many hereditary ocular diseases are rare and have little impact on the general population, but together they make up a significant group of visual impeding disorders. Over 60% of infant blindness is caused by hereditary eye disease such as eye malformations, optic atrophy, and retinal degeneration.

There has been tremendous headway in common ocular disorders as well. The two leading causes of visual acuity loss and blindness in adults are glaucoma and AMD, both of which genetic ophthalmologic researchers have shown to be hereditary in a large percentage of the patient population.

The beginning of 2018 witnessed the first ocular gene therapy approved by the FDA for retinitis pigmentosa (Spark Therapeutics’ voretigene neparvovec-rzyl), in where the mutated RPE65 gene–which normally delivers coding to create an enzyme that converts light to electrical signals–is replaced via subretinal injection to allow normal enzyme activity to return. This milestone paved the way for future approvals of genetic treatments, many currently in development or already in the clinic.

According to a recent article published in the International Journal of Ophthalmology, several ocular conditions have been identified and are being studied for genetic intervention, including:

  • Age-related Macular Degeneration (AMD)–complement factor and many other gene variants identified
  • Cataract–while genes associated with building of fiber cells along with homeostasis of lens proteins are thought to be key, more than 20 gene types have been identified
  • Glaucoma–several genes have been discovered with multiple interacting regions including defective genes such as optineurin and myocilin
  • Marfan Syndrome–a few genetic causes have been defined including mutations in fibrillin-1 that encodes protein fibrillin (a frameshift insertion and a nonsense mutation)
  • Myopia–more than a dozen linked genes including IGF-1 mutations
  • Polypoidal Choroidal Vasculopathies–phenotypically similar to AMD, but has a number of possible genes identified germane to PCV alone
  • Retinitis Pigmentosa–part of a group of heterogeneous diseases perpetuated via mutations in genes coding for proteins in rods and cones
  • Stargardt’s Disease–mutations in ABCA4 gene on chromosome 1 have been identified, with over 800 mutations
  • Uveal Melanoma–dysregulated signaling in multiple pathways have been identified including cyclin D1 overexpression, MDM2 overexpression, and P13K/AKT pathway

After four decades of researching gene therapy across multiple therapeutic areas, the ophthalmology field is filled with excitement as new treatments enter the clinic. The remainder of 2019 will certainly bring more advancements in genetic ophthalmology and move us closer to cures for many hereditary eye disorders.

More news