Clinical characteristics and current therapies for inherited retinal degenerations

Abstract

Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307-316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod-cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone-rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances.

Figure 1.

Fundus photographs, autofluorescence and spectral domain optical coherence tomography of a patient with rod–cone dystrophy (retinitis pigmentosa). Fundus photography (A right eye and B left eye), Fundus autofluorescence blue (C right eye and D left eye) and near infrared (E right eye and F left eye) as well as Sd-OCT (G horizontal scan, I vertical scan of the right eye, H horizontal scan and K vertical scan of the left eye) of a patient with rod–cone dystrophy (retinitis pigmentosa). On the color pictures note the waxy disc pallor of the optic disc, narrowed retinal vessels and preserved macular region with a high density ring of hyperautofluorescence around the macula associated with relatively preserved macular lamination on Sd-OCT.

Figure 2.

Adaptive optic images from the left eye of a patient with rod–cone dystrophy and perifoveal macular atrophy. (A) Infrared and blue autofluorescence from the left eye of the patient showing perifoveal loss of autofluorescence with relatively normal autofluorescence in the foveal region. (B) Sd-OCT horizontal scan of the left eye showing thinning of the outer retina with relatively normal foveal lamination with inner segment preservation up to 2°; white rectangles represent retinal location of the corresponding adaptive optics pictures. (C) Adaptive optics imaging reveals that cones are still present around the fovea, but the cone mosaic is nearly absent at 4°. (Image courtesy of Kiyoko Gocho and Michel Paques.)

Figure 3.

Fundus photographs, autofluorescence and spectral domain optical coherence tomography of a patient with Stargardt disease. Fundus photography (A right eye and B left eye), fundus autofluorescence blue (C right eye and D left eye), and near infrared (E right eye and F left eye) as well as Sd-OCT (G horizontal scan, I vertical scan of the right eye, H horizontal scan and K vertical scan of the left eye) of a patient with Stargardt disease. On the color pictures, note central macular atrophy with yellow dots in the mid-periphery. Fundus autofluorescence both on the blue and near infrared autofluorescence shows punctuate loss of autofluorescence in the mid-periphery with peripapillary sparing and loss of foveal autofluorescence in relation with macular atrophy; Sd-OCT reveal thinning of the outer retina in the foveal and parafoveal region.