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Weisenfeld Lecture: Progress being made toward biological treatment of retinal diseases

World-renowned retinal specialist Alan Bird, MD, FMedSci, University College London Institute of Ophthalmology and Moorfields Eye Hospital, London, received the Mildred Weisenfeld Award Monday evening and presented a lecture on progress toward biological treatment of retinal diseases. In his long career, Dr. Bird has made many contributions to the study of genetic and degenerative retinal disorders.

Fort Lauderdale, FL-World-renowned retinal specialist Alan Bird, MD, FMedSci, University College London Institute of Ophthalmology and Moorfields Eye Hospital, London, received the Mildred Weisenfeld Award Monday evening and presented a lecture on progress toward biological treatment of retinal diseases. In his long career, Dr. Bird has made many contributions to the study of genetic and degenerative retinal disorders.

Dr. Bird described some of the highlights of research on retinal dystrophies. Since 1969, when a genetic clinic for the study of retinal disease was established at Moorfields, enormous advances have been made. For example, investigators have identified the prevalence of different genetic forms of retinitis pigmentosa and the sequence of photoreceptor cell loss. They also have identified the genes involved and related the phenotype to the mutation, probed disease mechanisms, and initiated treatment.

About 20 years ago, researchers identified a mutation in the rhodopsin gene that caused retinitis pigmentosa. This discovery stimulated extensive efforts that so far have resulted in the identification of more than 130 genes and 42 loci linked to inherited retinal diseases, Dr. Bird said.

Advances also have been made in treatment of inherited retinal diseases, and research is underway on several approaches: growth factors, gene therapy, and cell transplantation. Gene therapy is likely to have the most immediate application, Dr. Bird said. In loss of function, the objective is to insert a gene that will work and produce proteins, while in other instances the goal is to block the function of the abnormal gene.

One of the first successes has been treatment of retinitis pigmentosa with RPE65, which has produced undoubted benefit in humans following successful treatment in a canine model, Dr. Bird said. While the extent of the benefit varies from patient to patient, researchers are planning to apply the therapy to younger individuals in the hope that earlier intervention will produce better results.

The next step will be applying gene therapy to other inherited retinal diseases, such as achromatopsia and choroideremia. Expanding gene therapy to more conditions could have a signifiant impact on blindness, Dr. Bird said.

The therapeutic advances that he cited in his award lecture are examples of the importation of knowledge from the laboratory to the clinic. This transfer justifies the existence of research institutes and organizations such as ARVO, which bring scientists and clinicians together, he added.

Dr. Bird also described his involvement during the 1970s with efforts to treat onchocerciasis, a parasitic condition which at that time was considered one of the major blinding diseases in the world.

“It had a limited distribution (mainly in sub-Saharan Africa), but it was the intensity of blindness that was so important,” he said, adding that a large proportion of the population in highly infected areas was destined to go blind before they died, and that life expectancy was limited.

Working with infected populations, Dr. Bird and other investigators learned more about the etiology and manifestations of onchocerciasis and eventually confirmed that the treatment recommended at the time by the World Health Organization was often detrimental, as local residents widely believed. It was found that the treatment caused major damage, including blindness, in some patients.

Dr. Bird was among those who contributed to the eventual use of the drug ivermectin, which kills the microfilariae that cause onchocerciasis. Along with vector control, this treatment has contributed substantially to the reduction of ocular morbidity, Dr. Bird said.

“Onchocerciasis is now not considered to be a major cause of blindness, although the disease has not been totally eradicated,” he concluded. “I feel extraordinarily fortunate to have taken part in this exercise, with many others, that has had a major effect on a blinding disease.”

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