**2. Theories of pathogenesis of vascular changes in macular dystrophies**

Histopathological studies in humans affected with macular dystrophies and in animal models of retinal degeneration demonstrated a wide-spread loss of the photoreceptors and the RPE, in addition to extensive vascular remodeling of the retinal vascular plexuses and the choriocapillaris [1, 2, 12]. These findings purported a cause–effect relationship between the morphological changes seen in retinal microstructure and the status of vascular nourishment, in the sense that one pathology is a consequence of the other, though the exact mechanism remains debatable [13–15]. One theory proposes that the progressive demise of photoreceptors and RPE causes a thinning out of the retina with subsequent progressive atrophy of retinal vasculature and choriocapillaris as part of a downregulation process due to a reduced vascular demand [16]. Another proposed mechanism is that retinal thinning due to the loss of photoreceptors and RPE allows more oxygen influx into the inner retinal layers from the choroidal circulation. The ensuing retinal hyperoxic state induces vasoconstriction and vascular rarefaction [12]. Another plausible theory is that progressive RPE loss results in a decreased release of vascular endothelial growth factor (VEGF) and other signaling factors that are essential for the viability of the choriocapillaris, hence precipitating choriocapillaris atrophy [17–19]. Finally, some researches propose that mechanical compression by the lipofuscin-laden RPE and accumulation of hyaline deposits between the RPE and Bruch's membrane exerts mechanical compression on the choriocapillaris with subsequent atrophy and loss [16].
