Research redefines retinal dystrophies

Baltimore-State-of-the-art evaluation and emerging therapies for retinal degenerations are currently the focus of significant research, said Hendrik Scholl, MD, MA, here at the 23rd annual Current Concepts in Ophthalmology meeting, held in association with Ophthalmology Times.

Dr. Scholl reviewed some of the newest modalities for imaging of the human retina and emerging treatment strategies for retinal dystrophies now in development.

In Germany, which is representative for Western societies, the most frequent single cause of blindness in those aged 20 to 60 years is the group of retinal dystrophies, said Dr. Scholl, visiting professor of ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore.

"This recent success has now left us with a complexity that is enormous," he continued. "Added to this complexity is genetic and phenotypic heterogeneity. For example, mutations in the rhodopsin gene are responsible for autosomal-dominant retinitis pigmentosa, autosomal-recessive retinitis pigmentosa, and for some forms of congenital stationary night blindness."

Molecular diagnosis is therefore a challenge, as is genetic counseling, according to Dr. Scholl.

"Moreover, we see that individual genes can cause different phenotypes," he said. "For example, mutations in the ABCA4 gene are responsible for recessive Stargardt's macular dystrophy. But they can also cause cone and cone-rod dystrophies, as well as full-blown retinitis pigmentosa. The picture is quite complex."

On the phenotypic side, retinal structure can now be investigated with effective tools that allow imaging of the retina with unprecedented resolution, Dr. Scholl explained.

"Multimodal imaging of the retina can be performed using confocal scanning laser ophthalmoscopy techniques using red-free, infrared, autofluorescence, fluorescein, or indocyanine green angiography," he said. "Simultaneously, we can use the latest technology in the field of optical coherence tomography."

To investigate retinal function, researchers use electrophysiology and psychophysics. For example, electroretinography is one of the techniques used to investigate retinal function objectively.

Psychophysical techniques are also useful, and include microperimetry with fundus control, which compensates for any eye movement.

The technique provides single sensitivity measures projected onto the retinal surface, Dr. Scholl said.

"We recently correlated visual function with multimodal imaging techniques in macular telangiectasia, and found that there is a significant relationship between outer retinal thickness and retinal sensitivity," he said. "Longitudinal data revealed that small lesions affecting the photoreceptor layer typically precede functional detection but later cause severe loss of light sensitivity."

Ranibizumab, he said, was shown to be ineffective to prevent such functional loss in macular telangiectasia.²