Abstract
Purpose :
The mild phenotype associated with point mutations in the gene RGR (Retinal G-protein-coupled Receptor) entails mild asymptomatic anomalies of retinal pigment epithlium (RPE) around the optic disc; and the contrasting severe phenotype entails loss of central vision from choroidal sclerosis. This study bridges the gap between these extremes by showing progression of disease in one individual over almost three decades.
Methods :
This study entails clinical observation with fundus photography, fluorescein angiography, optical coherence tomography and visual field testing. The individual concerned is the proband in a family where six members in three generations have asymptomatic anomalies around the optic discs, and one other member has lost central vision due to chorio-retinal degeneration.
Results :
In teenage the proband had areas of anomalous discolouration of the RPE under the nasal half of each macula and around each disc, and dense scotomata in the corresponding portions of visual field. The remaining unaffected RPE remained normal throughout follow-up; but secondary pathology slowly appeared in the choriocapillaris underneath the abnormal RPE, and subsequently in the larger choroidal vessels. As colobomata opened up in the nasal sub-macular choroid the healthy part of the RPE was shown to slide temporally under the fovea.
Conclusions :
The slowly progressive degenerative changes that we have observed in the choroid underlying affected areas of RPE demonstrates that the choroid has some sort of trophic dependence upon healthy RPE and choroid, and that when the RPE is damaged by the point mutation in RGR the lack of that trophic effect leads, very slowly, to degeneration first of the choriocapillaris and then of the larger choroidal vessels. This explains how RGR point mutations can be associated with severe as well as with mild phenotypes, but we still do not understand why the only portion of RPE (and sometimes of choroid) to be affected is around the optic disc and under the nasal part of the macula. The trophic dependence of choroid upon RPE that is illuminated by this study may be applicable to other situations: we can look for comparably slow deterioration of the subjacent choroid where the RPE is damaged by ripping, atrophic macular degeneration, or other hereditary disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.