Dear Editor, I have some ideas about macular edema and macular ischemia in diabetic retinopathy, and the recent case report by Dr. Hayreh  refreshes these ideas and I would like to explain them. I start the discussion with reviewing some well-known facts of physiology: In normal individuals, because of autoregulatory function of pericytes, high blood pressure in perifoveal arterioles leads to a decrease in their caliber. This vasospasm protects vessels from high pressure inside them and reduces wall tension  (recall that pressure declines in smaller diameter tubes (Bernoulli’s law) and wall tension as a function of Pressure* Radius decreases when the two above variables decrease). Diabetes patients lose the pericytes and their autoregulatory function, so high blood pressure in perifoveal capillaries results in exudation and more destruction of the vessel wall. Exudation and macular edeme lengthen the distance for simple diffusion to supply oxygen and nutrients, causing ischemia, which in turn results in more exudation. This loop of exudation–ischemia results in diabetic maculopathy. Considering that the inner retina in the foveal avascular zone is markedly dependent upon simple diffusion from very small capillaries of perifoveal area, not only ischemia may result in macular edema by increasing capillary permeability but also macular thickening and edema exacerbates the hypoxic state due to lengthening of the path for diffusion. It is well known that the control of blood pressure in diabetics may result in a decrease in macular edema by breaking the exudation hand of the above-mentioned loop. Control of kidney function and proteinuria also lead to a decrease in exudation of fluid and reduction in exudation hand of this loop. Management of anemia by supplying more oxygen to the tissues is an effective treatment by breaking down the ischemia side of this cycle.  Although macular ischemia as a result of very low blood pressure may be an explanation for the Dr. Hayreh case, some other interesting and well-known mechanisms could also explain his findings. Anemia (and its consequence, hypoxia) as either a side effect of medication (ACEI side effect)  that was used by the patient or her underlying disease (diabetes and its nephropathy) may explain macular edema and subfoveal fluid in her OCT (optical coherence tomography). Proteinuria might result in more exudation and macular edema in this patient as well. In addition to NAION (nonarteritic anterior ischemic optic neuropathy) in this patient, coexisting non-ischemic CRVO (central retinal vein occlusion), which might have a self-limiting process, should also be kept in mind. Obvious venous tortuosity and dilation and widespread hemorrhage throughout the fundus and far from the macula that is seen in initial fundus angiography of the patient’s right eye and its disappearance in the final angiography may be due to non-ischemic CRVO in concordance with NAION.