A Revolution in Ocular Genetics

American Academy of Ophthalmology 2012

Alex V. Levin, MD, MHSc


November 20, 2012

Editorial Collaboration

Medscape &

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Hello. I'm Dr. Alex Levin, Chief of Pediatric Ophthalmology and Ocular Genetics at Wills Eye Institute in Philadelphia. Welcome to Medscape Ophthalmology Insights. This is part of a series in collaboration with Medscape and Wills Eye Institute. We are coming to you from the American Academy of Ophthalmology (AAO) meeting in Chicago, and we want to bring you up to date on the latest developments in ocular genetics.

We live in exciting times. With the explosion in knowledge about the genetic basis of disease, we now have new diagnostic power to help patients understand their illnesses and guide their physicians to better intervention strategies. Ophthalmology has led the pack largely because of the unique opportunity for us to see genetic events occurring "live," something that can’t be done with any other organ. It is no wonder that the first autosomal dominant, autosomal recessive, X-linked recessive, X-linked dominant, digenic, triallelic, mitochondrial, and 2-hit disorders all had eye manifestations or were primarily eye diseases. We can actually see the lyonization taking place in the retina of a female carrier of ocular albinism or Lowe syndrome. As a result of this advantage, we now have wide diagnostic opportunities to find the genetic basis of a patient's eye disease.

With those opportunities come some challenges. Diseases such as retinitis pigmentosa have scores of genes which, when mutated, can cause the disorder. We have had to rename diseases such as albinism from the old tyrosinase positive and -negative to a complicated, gene-based nomenclature for oculocutaneous albinism: OCA1, OCA2, etc. The genetics of glaucoma and cataract are proving to be complex with multiple involved loci. Yet, finding the causative gene helps the patient move beyond the unknown into the world of knowing what they have, what the future might hold, recurrence risk assessment, identification of at-risk family members, contact with appropriate support groups, knowledge of what else to look for, appropriate surveillance screening, and, of greatest importance, the new possibility of gene-based treatment.

With the successful phase 1 and 2 trials on children and adults with Leber congenital amaurosis caused by mutations of the RPE65 gene, we expect an explosion of gene therapy trials in the near future for diseases such as choroideremia, Usher syndrome, retinoschisis, and more. In addition, at places like Wills Eye Institute in Philadelphia, we already have trials under way for stem cell treatment and artificial retina implantation for genetic retinal disorders. Yes, trials take time, and they may begin with 1 eye of affected adults rather than well-seeing young children before vision loss, but the door is open and the question now is, how can we best help our patients walk through that door?

Part of the difficulty is that the general ophthalmologist cannot possibly be expected to diagnose these rare disorders, keep up-to-date with the exploding genetic information, know how to solve complex genetic dilemmas or select appropriate testing (let alone interpret the results of those tests), or be able to identify appropriate treatment trials for the patients. Examining these patients and solving their mysteries takes hours of work, both during and after the clinical contact.

That is where the field of ocular genetics comes into play. Although still representing a small fraction of ophthalmic subspecialists, ocular genetics programs, such as the one at Wills Eye Institute, can now be found at some centers. These programs offer the experience and knowledge to assist ophthalmologists in the diagnosis, testing, interpretation, support, and eventual treatment of patients with genetic eye disease. Ocular genetics represents a paradigm shift in ophthalmic patient care. No longer is it common to say, "I'm sorry but I don't know what you have" or "I'm sorry, but there is nothing I can do; your child will be blind." The rapid advances occurring every day in ocular genetics at Wills Eye Institute and elsewhere now allow us to give our patients hope, if not promise, for the future and the power of understanding and support that will give them strength today.

Thank you for joining us. I'm Dr. Alex Levin for Wills Eye Institute and Medscape Ophthalmology.