Kreissig lecture highlights role of choroidal ischaemia in AMD

An improved understanding of the role of choroidal ischaemia in the pathogenesis of age-related macular degeneration (AMD) may lead to better and more targeted therapies for the treatment of the disease, said Donald Jackson Coleman MD, FACS, in the Kreissig Lecture delivered at the 17th EURETINA Congress. “The theory that choroidal and retinal blood flow abnormalities play a role in AMD is now well established. We know that ischaemia is present in nearly all cases of AMD but that fact does not preclude the presence of other aetiologies such as oxidative stress and genetics in the development of the disease. The key point is that ischaemia can be successfully treated,” he said. The research of Dr Jackson Coleman and colleagues in this area have led them to hypothesise that choroidal ischaemia is related to a parasympathetic control similar to that in pulmonary arterial hypertension and erectile dysfunction. Sildenafil (Viagra, Pfizer), a selective phosphodiesterase (PDE) inhibitor, has been shown to increase choroidal perfusion and may thus have a beneficial effect on delaying or interdicting AMD. By inhibiting PDE5, sildenafil enables the terminal arterioles in Sattler’s layer of the choroid to increase nitric oxide perfusion and help in the reduction of toxic waste products, said Dr Jackson Coleman. Its inhibition of PDE6 leads to a decrease in basal rod photoreceptor hypoxic drive. In an off-label treatment of four AMD patients treated with 20mg of sildenafil over a four- to six-year period, Dr Jackson Coleman said that the therapy seemed to be safe and effective. “All patients noted an increase in their contrast sensitivity and their visual acuity remained stable over the follow-up period and maintained at pre-treatment levels,” he said. Further investigation with optical coherence tomography (OCT) imaging showed that soft drusen decreased with the use of sildenafil and there seemed to be visible recovery of the photoreceptor layer. Dr Jackson Coleman said that the drug had no detrimental effect on best-corrected visual acuity (BCVA), contrast sensitivity, colour vision or intraocular pressure. The study demonstrates proof of concept but many questions remain to be answered in future research, he added. “We need to think about timing and when we should start therapy, and to ask if treating patients earlier might prevent progression of AMD. We also need to address questions of dosage and potentially adjusting for different body weights. Finally, we need to compare the performance of sildenafil with new systemic therapies for mitochondrial health and investigate whether treatments might also be helpful in other conditions such as retinitis pigmentosa and stem cell therapies,” he concluded.