Structural and functional assessment of cone photoreceptors in patients with rhodopsin mutation.

Abstract

Purpose: To evaluate functional and structural changes over time in patients with autosomal dominant rod-cone dystrophy (adRCD) due to rhodopsin (RHO) mutation.

Methods: 28 patients from our cohort of 50 RCD patients with RHO mutation were enrolled in the study. Best-corrected visual acuity (BCVA) was measured with the ETDRS chart. Central retinal sensitivity was assessed, in the 8° at baseline and 12° at 1 and 2 years of follow-up using microperimetry (Nidek MP1, Padova, Italy). Fundus autoflourescence (FAF, HRA2, Heidelberg, Germany) was performed in all patients at baseline and in 19 patients at follow-up visits. If a perifoveal ring of increased FAF was present the surface and diameter along the horizontal axis inside the ring was measured. Spectral domain optical coherence tomography (sd-OCT, Spectralis, Heidelberg, Germany) was obtained in 28 patients at baseline and in 19 patients at follow-up visits. Preservation of the ellipsoid zone was measured along the horizontal axis and correlated with visual acuity, microperimetry and FAF.

Results: Among the 28 patients 17 were women and 11 men. Patient’s age ranges from 11 to 66 years. BCVA was between 20/20 to LP. None of our patients presented normal autofluorescence: 10 had a ring of increased FAF and 18 showed patchy loss of FAF in the macula. Slight constriction of horizontal diameter and surface of the ring was observed over the study and was in correlation with the ellipsoid zone thinning measured on sd-OCT. Visual sensitivity inside, across and outside the autofluorescent ring was 11.66 +/- 5.76; 7.87+/-5.0 and 1.4+/-2.3 dB respectively. In the eyes without the hyperfluorescent ring (irregular autofluorescence) central retinal sensitivity was markedly diminished.

Conclusions: There is a variability in macular FAF abnormalities in patients with rhodopsin mutations. Only 30% presented with a ring of increased FAF associated with macular function and structure preservation as documented by microperimetry and sd-OCT respectively. These findings may suggest variable macular cone involvement associated with the genotype and could serve basis for future clinical trials based on gene therapy or neuroprotection for cone survival.

Keywords: 696 retinal degenerations: hereditary • 550 imaging/image analysis: clinical