Supplemental Digital Content is Available in the Text.Safety assessment of subretinal implantation of human embryonic stem cell–derived retinal pigment epithelium to repopulate the retinal pigment epithelium cells in the submacular area in Stargardt disease.

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To provide information on the effects of phosphodiesterase type 5 (PDE5) inhibitors on choroidal vessels and central serous chorioretinopathy (CSC) and possible implications for development of exudative age-related macular degeneration (AMD). Two independent investigators conducted a qualitative review of PubMed to identify studies on the choroidal effect of PDE5 inhibitors in June 2019. The search used key words that included PDE5 inhibitors, sildenafil, tadalafil, vardenafil, choroid, choroidal flow, choroidal vessels, choroidal thickness, CSC, AMD or a combination. Only studies which assessed choroidal findings were included. Many ocular diseases are related to changes in choroidal thickness and perfusion. Patients with AMD, who have decreased choroidal perfusion, may manifest more severely diminished choroidal ability to deliver oxygen and other metabolites to the retina, leading to growth of neovascular tissue. As a result of this engorgement of the choroidal vasculature, some patients may have leakage across the retinal pigment epithelium (RPE) and accumulation of subretinal fluid, resulting in CSC. Transient visual symptoms, i.e., changes in color perception and increased light sensitivity, are well-known adverse effects, but there have been rare reports of vision-threatening ocular complications in users of PDE5 inhibitors, such as nonarteritic anterior ischemic optic neuropathy and cilioretinal artery occlusion. The choroid is a vascular tissue analogous in many respects to the corpus cavernosum, and PDE5 inhibitors may increase the choroidal thickness and perfusion. While it is intuitively obvious that thickness of the choroid alone does not guarantee better choriocapillaris oxygenation, it is a reasonable step towards ameliorating ischemia. These drugs have numerous physiologic effects on the choroid related to blood flow, such as clinical consequences in CSC and AMD.