TABLE 1.

Key differences in the application of gene-based therapeutics for inherited and acquired retinal diseases.

Monogenic inherited retinal disease	Multifactorial acquired retinal disease
Genotype-specific; Relies on accurate identification of the causative genetic variant in individual patients	Genotype-agnostic; Does not require identification of causative genetic variants in individual patients
Therapeutic targets and pathophysiologic pathways are genotype-specific	Therapeutic targets and pathophysiologic pathways may not be disease-specific; e.g., VEGF pathway is common to neovascular AMD, DR, RVOs
Treatment and delivery are targeted at specific cell types and locations, e.g., photoreceptors at the macula	In “ocular biofactory” approaches, treatment and delivery do not have to be targeted at specific cell types or locations
Smaller treatment population per therapy developed; Translates to higher cost per treatment; However, may qualify for “orphan drug” designation	Larger potential treatment population per therapy developed; May translate to lower cost per treatment; Most diseases will not qualify for “orphan drug” designation
Possibility of prophylactic therapy, e.g., in utero or pre-implantation, only if diagnosis is suspected or known at that stage	Possibility of prophylactic therapy at earlier stages of disease, e.g., early or intermediate AMD, non-proliferative DR
Lower bar for acceptance in terms of safety and efficacy; Standard of care is largely expectant management	Higher bar for acceptance; Safety and efficacy need to be compared against standard of care treatment, e.g., intravitreal anti-VEGF therapy or laser photocoagulation
Blood-retinal barrier more likely to be intact; Less potential for systemic immunogenicity	Blood-retinal barrier may be compromised; May have greater potential for systemic immunogenicity

VEGF, vascular endothelial growth factor; AMD, age-related macular degeneration; DR, diabetic retinopathy; RVO, retinal vein occlusion.