Treatment of Macular Degeneration with Sildenafil: Results of a Two-Year Trial

Abstract

Objective: To evaluate PDE5/6 inhibition with sildenafil to reduce choroidal ischemia and treat age-related macular degeneration. Methods: Sildenafil was prescribed to treat participants with macular degenerations or macular dystrophies measured by spectral-domain optical coherence tomography, color fundus photography, enhanced depth imaging, and best-corrected visual acuity. Results: No change in calcified drusen was noted. Vitelliform-type soft drusen were not substantially changed. A participant with Best vitelliform macular dystrophy had a significant improvement in vision as well as in photoreceptor and ellipsoid layers. Conclusions: Our research supports sildenafil as a safe treatment for age-related and vitelliform macular degenerations. Thickened Bruch’s membrane reduces the beneficial effect of perfusion increase, but all eyes appear to benefit from PDE6. Notably, maintenance or improvement in the photoreceptor layer may be the most significant result of sildenafil and is consistent with PDE6 inhibition. Thus, sil­denafil treatment of macular degeneration offers significant potential for vision retention and recovery.

Identification of Key Genes and Pathways Associated with Age-Related Macular Degeneration

“…Rho kinase inhibitors also have a potential therapeutic benefit in neovascular AMD [37]. Phosphodiesterase (PDE) inhibitors, including Viagra (sildenafil; Pfizer [38]), Levitra (vardenafil; Bayer), and Cialis (tadalafil; Eli Lilly), continue to raise interest among eye specialists for the hypoperfusion-related ocular pathologic disease treatment, including diabetic retinopathy and AMD [39]. G protein alpha was released by the activation of GPCRs, which provided a strategy for AMD treatment from a system pharmacology aspect [18].…”

Central serous chorioretinopathy treatment with a systemic PDE5 and PDE6 inhibitor (sildenafil)

“…Our hypothesis is that select patients with macular disease including CSCR may benefit from increased choroidal blood flow afforded by sildenafil. 14 , 15 , 16 We anticipate that sildenafil, administered with attention to “challenge” and “dechallenge” settings - that is, continued treatment beyond the initial resolution of serous fluid - should produce clinical improvement for these patients. The use of spironolactone – and eplerenone to a lesser extent - most closely parallels the present treatment but has shown slower treatment response and greater side effects.…”

Effects of phosphodiesterase type 5 inhibitors on choroid and ocular vasculature: a literature review

“…Systemic treatment using a PDE5 and PDE6 inhibitor (sildenafil) is suggested as a means of increasing choroidal perfusion. Based on the hypothesis of increasing choroidal perfusion as a means of elevating NO (a messenger molecule) transfer across Bruch's membrane by PDE5 as well as the increase in photoreceptor regeneration caused by a decrease in Warburg glycolysis by PDE6, some studies treated a series of patients with AMD with systemic sildenafil [20].…”

“…Coleman et al [20] conducted a 2-year trial to evaluate the effect of sildenafil measured by spectral-domain OCT, color fundus photography, EDI, and best-corrected visual acuity. The group concluded that sildenafil is a safe treatment for AMD or vitelliform macular degeneration and suggested that a thickened Bruch's membrane reduced the beneficial effect of the perfusion increase, but all eyes appeared to benefit from PDE6.…”