Retinal dystrophies (RDs) comprise relatively rare but devastating causes of progressive
vision loss. They represent a spectrum of diseases with marked genetic and clinical
heterogeneity. Mutations in the same gene may lead to different diagnoses, for example,
retinitis pigmentosa or cone dystrophy. Conversely, mutations in different genes may
lead to the same phenotype. The age at symptom onset, and the rate and characteristics
of peripheral and central vision decline, may vary widely per disease group and even
within families. For most RD cases, no effective treatment is currently available.
However, preclinical studies and phase I/II/III gene therapy trials are ongoing for
several RD subtypes, and recently the first retinal gene therapy has been approved
by the US Food and Drug Administration for RPE65-associated RDs: voretigene neparvovec-rzyl
(Luxturna). With the rapid advances in gene therapy studies, insight into the phenotypic
spectrum and long-term disease course is crucial information for several RD types.
The vast clinical heterogeneity presents another important challenge in the evaluation
of potential efficacy in future treatment trials, and in establishing treatment candidacy
criteria. This perspective describes these challenges, providing detailed clinical
descriptions of several forms of RD that are caused by genes of interest for ongoing
and future gene or cell-based therapy trials. Several ongoing and future treatment
options will be described.