Late-Onset Retinal Macular Degeneration: refining the phenotype

Abstract

 

Purpose

 

Late-onset retinal macular degeneration (L-ORMD) is a rare inherited blinding eye disease. L-ORMD and age-related macular degeneration (AMD) share key clinical characteristics including macular drusenoid spots, choroidal neovascularisation and retinal atrophy. At onset, the diseases are difficult to differentiate. Importantly, a translational pathway now exists for new therapies through human induced pluripotent cell, small animal model, large animal model and identified L-ORMD families. Current phenotyping methods, although informative, do not enable adequate assessment of treatment efficacy. Together these indicate a need to develop better quantifiable clinical markers. This study aims to see if new-generation retinal diagnostic tools can provide clinically useful phenotypic markers using one of the largest L-ORMD patient cohorts.

 

Methods

 

We initially recruited 17 affected cases across two regions in the United Kingdom. Patients had an average age of 63 with 11 male: 6 female ratio. We investigated patients using microperimetry, multifocal ERG, scanning laser ophthalmoscope and HD-OCT, fluorescein angiogram and indo-cyanine green.

 

Results

 

Mean visual acuity for the patients was 0.52(-0.06-1.38) right eye and 0.64(-0.1-1.56)left eye. In early stage 2 disease patients microperimetry was most sensitive from 10 degrees temporal to fovea(Fig 1) and correlated well with reduced multifocal ERG sensitivity. Fluorescein angiogram showed early hyperfluorescent white dots with plaque at macula. ICG showed hypofluorescent mid-peripheral stippled appearance. Hypofluorescent areas at the macula corresponded to white dots seen on colour photograph. HD Oct showed no significant thickening in early stage patient’s macula.(Fig 2)

 

Conclusions

 

We have previously described a staging system for L-ORMD. In intermediate stages, microperimetry, multi focal ERG and autofluorescence help to further characterise the L-ORMD phenotype by highlighting changes to the temporal retina despite little fundus change. These changes appear different from those commonly seen in AMD. This study provides a useful baseline for a long-term cohort study and future planned treatment studies.

 

 

Figure 1 Showing marked temporal microperimetry sensitivity loss despite few fundus changes

 

 

Figure 2 Colour fundus(A, B), SLO (C, D), FFA(E, F) and ICG(G, H)

 

Keywords: 688 retina • 494 degenerations/dystrophies • 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)