Ischemic Retinal Vein Occlusion: characterizing the more severe spectrum of retinal vein occlusion

Retinal vein occlusion (RVO), including central (CRVO), branch (BRVO) and hemicentral and hemispheric RVO, is the second most common vascular cause of visual loss, surpassed only by diabetic retinopathy. The presence and extent of retinal ischemia in RVO is associated with a worse prognosis. On this basis, most previously conducted studies considered iRVO and non-iRVO as separate entities based on set thresholds of existing retinal ischemia, as determined by fundus fluorescein angiography (FFA). Other diagnostic technologies have been used specifically in the differentiation of iCRVO and non-iCRVO. To date there is not a fully accepted definition for iRVO. Some clinicians and researchers may favor establishing a clear differentiation between these forms of RVO; others may prefer not to consider iRVO as a separate entity. Whatever the case, retinal ischemia in RVO confers a higher risk of visual loss and neovascular complications and, thus, should be determined as accurately as possible in patients with this disease and should be considered in clinical and experimental studies. Most recently conducted clinical trials evaluating new treatments for macular edema secondary to RVO, included none or only few patients with iRVO based on previous definitions (i.e. few patients with sizeable areas of retinal ischemia were recruited in these trials) and, thus, it is unclear whether the results observed in recruited patients could be extrapolated to those with retinal ischemia. There has been scarce research aiming at developing and/or testing treatments for retinal ischemia as well as to prevent new vessel formation result of RVO. This manuscript aims at providing the reader with a detailed review on the knowledge gathered over the years on iRVO, from controversies on its definition and diagnosis to the understanding of its epidemiology, risk factors and pathogenesis, the structural and functional effects of this disease in the eye and its complications, natural history, and outcomes following treatment. In each section, the definition of iRVO used is given so, independently of whether iRVO is considered a separate clinical entity or a more severe end of the spectrum of RVO, the information contained herein will be useful to clinicians, to determine patient's risk, guide therapeutic decisions and counsel patients and for researchers to design future studies.