by Robert Hammer, B. Optom.
January 2002
The gene for Stargardt’s disease has been identified (Allikmet et al.’97 Nat. Gen. 15:236-246). The faulty gene fails to code for a protein which is present in rod outer segments only (has not been found in cones, pigment epithelium or anywhere else in the body). This protein was thought to be responsible for the active transport of some substance across the cell membrane.
Recently published findings (Weng at al. ’99 Cell 98: 13-23) yield a model identifying this substance as a compound of a product of the phototransduction of rhodopsin (protonated N-retinylidene-PE). As a result, protonated N-retinylidene-PE, a precursor of lipofuscin, is present in higher concentrations in rod outer segment discs with the Stargardt’s defect than in normals.
These rod outer segment discs are phagocytosed by RPE cells, where, over time, high levels of lipofuscin accumulate. High lipofuscin concentrations in the long term can have a detergent-like effect, destroying the RPE cell. These “poisoned” RPE cells, in turn, fail to support the existence of the photoreceptors. This is significant mainly in the perifovea, where rod density is maximal, leading to the characteristic macular degeneration. This correlates with histopathological findings of high lipofuscin levels in the RPE in Stargardt’s (and also in some cases of AMD).
At the end of their discussion, the authors predict from their model that avoiding bright light (and hence the phototransduction of rhodopsin) would help slow the progression of Stargardt’s disease. I would go one step further than just suggesting dark glasses when outdoors. In view of the fact that the gene is expressed in rods only and not in cones, I would consider colored lenses (for both outdoors and indoors) which specifically filter out wavelengths which stimulate rod vision, while still allowing cone vision. (Rod cells are not sensitive to wavelengths exceeding 600 nm, while cone cell sensitivity extends to 700 nm.)
There are a number of ways of achieving this. I think that the lenses prescribed need to be individually tailored for each patient, taking into account his level of motivation to slow down the degeneration, balanced against cosmesis, distortions, color vision, and functional visual requirements. There is room for creativity in prescribing appropriate protection for Stargardt’s patients.
At one extreme would be red filters which don’t transmit any light of wavelength shorter than 600 nm. This would be expected to provide complete protection and delay indefinitely the progress of the disease, but I think that almost no one would wear them. The other extreme is wearing regular sunglasses when outdoors.
I have an 8.5 year old patient with suspected early Stargardt’s. I provided him with a pair of lenses with a filter which blocks out all light shorter than 550 nm. I chose the lighter lens, intending that he would use them both indoors and outdoors, and I also incorporated his prescription.
In practice, he uses them only outdoors. They distort color vision too much to be acceptable to him for full time wear. He was concerned about the cosmetic appearance of the bright orange color of the lenses, so I provided a regular grey clip-on over the spectacles. This provides a very satisfactory appearance, and he is comfortable using it outdoors, although the distortion to color vision is a bit disturbing.
In conclusion, clinical application of the latest research findings provides hope to patients with early Stargardt’s for delaying or slowing the progress of the disease until gene replacement therapy becomes available.
