Age-related macular degeneration (AMD) is a multifactorial progressive degeneration of macula and it is the major cause of irreversible blindness in senile population in developed world. According to World Health Organization (WHO), about 10% of blindness is due to AMD. About 196 million individuals are affected by AMD worldwide.^[1]

Several genetic and environmental risk factors are associated with AMD. Aging is the strongest non-modifiable risk factor whereas smoking, obesity, atherosclerosis, hypertension, hyperlipidemia are moderate and modifiable risk factors. Oxidative stress, altered hemodynamics, immune inflammatory responses play important role in pathogenesis of AMD.^[2] AMD is usually classified into dry (non-exudative) and wet (exudative) forms. The dry form is more common comprising around 80 -90% of cases.

A positive family history increases the risk of AMD.^[3] Klaver CC et al. reported one in four cases of advanced AMD is genetically determined.^[4] Important genes implicated in AMD are: CFH (Compliment factor H), HTRA-1 (Htra Serine Peptidase-1) and ApoE (apolipoprotein- E) etc.^[2] CFH inhibits multiple steps of the alternate pathway of inflammation. It binds with C-reactive protein (CRP) and inhibits the CRP-mediated response to photoreceptor damage. The Y402h mutation in the CHF gene may lead to complement dysregulation in AMD.^[5], ^[6], ^[7] Single-nucleotide polymorphisms (SNPs) in chromosome 10q26 are associated with high risk of wet AMD.^[8]

Ischemia-induced neovascularization of photoreceptor involves release of HIF-1 (Hypoxia inducible factor-1) and vascular endothelial growth factor (VEGF) that can be modulated by gene therapy.

rAAV2-sFLT1 treatment is used for prolonged management of neovascular AMD. Adeno-associated virus type 2 (AAV2)-sFLT1 combines a viral factor with plasmid which transduce retinal cells to produce highly potent naturally occurring anti VEGF (sFLT1=fms-like tyrosine kinase). Phase I/ IIa trial established safety and efficacy of rAAVs FLT1.^[9] It improves central macular thickness and regain vision.

ADVM-022 / ADVM-032 - utilize a modified AAV2 vector which is specified for intravitreal infections, ADVM-022 expressing an aflibercept-like protein while ADVM-032 producing a ranibizumab like protein.^[2]

Retinostat utilizes a recombinant equine infectious anemia virus (EIAV) vector which encodes two protein - endostatin and angiostatin through a subretinal injection. The phase-1 trial has been done for neovascular AMD without any adverse effects.^[10]

AKST4290- is an oral treatment that targets against CCR3 which is receptor for eotaxin. Eotaxin is associated with membrane permeability in pathogenesis of AMD. Phase II trial showed improvement in BCVA of 2-83Y of wet AMD.^[11]