Update on current and future novel therapies for dry age-related macular degeneration

Abstract

Age-related macular degeneration (ARMD) is the leading cause of irreversible blindness in developed countries. There are currently no cures, but there are promising potential therapies that target the underlying disease mechanisms of dry ARMD. Stem cells, ciliary neurotrophic factor, rheopheresis, ozonated autohemotherapy and prostaglandins show promise in stabilizing or improving visual acuity. Age-Related Eye Disease Study vitamins may reduce progression to severe ARMD. Adjuvant therapy like low vision rehabilitation and implantable miniature telescopes may help patients adjust to the sequelae of their disease, and herbal supplementation with saffron, zinc monocysteine and phototrop may be helpful. Therapies that are currently in clinical trials include brimonidine, doxycycline, anti-amyloid antibodies (GSK933776 and RN6G), RPE65 inhibitor (ACU-4429), complement inhibitors (ARC1905, FCFD4514S), hydroxychloroquine, intravitreal fluocinolone acetate and vasodilators like sildenafil, moxaverine and MC-1101. Therapies that have not been shown to be effective include POT-4, eculizumab, tandospirone, anecortave acetate, the antioxidant OT-551, sirolimus and vitamin E.

Keywords::

• amyloid-β antibodies
• AREDS
• ciliaryneurotrophic factors
• complement cascade
• lasers
• macular degeneration
• rheopheresis
• stem cells

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Age-related macular degeneration is a leading cause of blindness in the world.

• • Therapies that may stabilize or improve vision include stem cells (regenerates photoreceptors), CNTF (mediates the IL-6 pathway), rheopheresis (filters out large molecular weight protein), ozonated autohemotherapy (improves oxygenation), prostaglandins (upregulates glutathione) and saffron.

• • Glatiramer acetate and lasers may decrease drusen, autologous retinal transplantation can be anatomically successful, fenretidine may decrease the size of geographic atrophy and incidence of CNV, sildenafil increases choroidal thickness and retinal vascular flow, carotenoids and ω-3 fatty acids may decrease progression of geographic atrophy. However, these therapies do not improve vision.

• • Low vision rehabilitation and implantable miniature telescopes may help patients cope with their disease.

• • Potential treatments pending results include brimonidine, doxycycline, immunoglobulin GSK933776, anti-amyloid-β RN6G, RPE65 inhibitors (ACU-4429) and complement component 5 inhibitor (ARC1905), complement factor D inhibitor (FCFD4514S), hydroxychloroquine, steroids, rosemary and tumeric.

• • Treatments that lacked efficacy include the steroid anecortave acetate; antioxidant OT-551; sirolimus; complement inhibitors POT-4, eculizumab and tandosporine; vitamin E alone; and gingko biloba.