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D Jackson Coleman, Stanley Chang, Stephen H Tsang, Suzanne Daly, Winston Lee, Harriet O Lloyd, Ronald H Silverman; Systemic treatment of macular degeneration with sildenafil. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4975. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Choroidal ischemia is related to parasympathetic control of the choriocapillaris, similar to parasympathetic regulation in pulmonary hypertension and erectile dysfunction. With choroidal ischemia, the terminal arterioles in the Sattler layer of the choroid can be upregulated with a phosphodiesterase-5 (PDE5) inhibitor to increase nitric oxide perfusion and reduce toxic waste products (Starling’s Law)1. Sildenafil also cross-reacts with phosphodiesterase-6 (PDE6), which normally promotes acidosis and Warburg anabolism. Decreased photoreceptor Warburg anabolism and outer segment genesis decrease retinal pigment epithelium (RPE) metabolic stress. In a previous long-term series of sildenafil treatment we found positive visual effects2,3. The purpose of this current study is to evaluate the effects of systemic sildenafil on macular degeneration including hard and soft drusen, as well as acquired and inherited vitelliform lesions in a more diverse patient population.
Six subjects are being treated with systemic sildenafil, 20 to 40 mg twice daily, with dosage based on patient weight. Best-corrected visual acuity (BCVA), color fundus and autofluorescence imaging, Pelli-Robson contrast sensitivity and spectral domain-optical coherence tomography (SD-OCT) mapping of the macula is performed every 2 months.
There is improved contrast sensitivity, maintenance of BCVA and evidence on SD-OCT of sub-pigment epithelial detachment absorption after one year follow-up. Other changes include decreased lipid in soft (vitelliform-type) lesions but no observed changes in hard drusen.
Systemic PDE5 inhibitors such as sildenafil may have a positive effect in treating macular degeneration and may offer enhancement of intravitreal injection of anti-VEGF agents in wet AMD. Vision is retained by increased choroidal perfusion and unique metabolic support of the photoreceptor layer.REFERENCES:1. Flower RW, Fryczkowski AW, McLeod DS. Variability in choriocapillaris blood flow distribution. Investigative ophthalmology & visual science 1995;36:1247-1258.2. Kim DY, Silverman RH, Chan RV, et al. Measurement of choroidal perfusion and thickness following systemic sildenafil (Viagra((R)) ). Acta ophthalmologica 2013;91:183-188.3. Coleman DJ, Silverman RH, Rondeau MJ, Lloyd HO, Khanifar AA, Chan RV. Age-related macular degeneration: choroidal ischaemia? The British journal of ophthalmology 2013;97:1020-1023.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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