Vision loss caused by diabetic retinopathy comes in different packages.
Vision loss caused by diabetic retinopathy comes in different packages. Some form of vision loss can be reversable, for instance, when associated with diabetic macular edema (DME), vitreous hemorrhage, and tractional retinal detachment. However, vision loss associated with neovascular glaucoma and tractional retinal detachment involving the macula may not be recovered.
Loss of vision associated with macular and/or retinal ischemia may not only be irreversible, it is also the precursor for the above-mentioned complication.
Retinal ischemia results in upregulation of vascular endothelial growth factor (VEGF),1 a mediator of increased vascular permeability resulting in retinal edema and angiogenesis resulting in retinal neovascularization.
Retinal ischemia is referred to by a different lexicon and depends on the context in which it is discovered. For example, an angiographic term such as capillary dropout and/or capillary and vascular nonperfusion is used to describe this finding. Clinically, ischemic retinal changes may be difficult to detect.
Identifying retinal ischemia
The clues suggesting presence of an ischemic or hypoxic retina include cotton-wool spots. These fluffy white retinal lesions located in the retinal nerve fiber layer (RNLF) are representative of accumulation of axoplasm, caused by localized or diffuse ischemia. Although these don’t cause generalized ischemia, once they disappear, they result in localized RNFL loss (Figure 1).
Other clinical clues suggesting retinal hypoxia include presence of venous beading and loops, occluded (ghost) arteries and arterioles, retinal and/or iris neovascularization, preretinal hemorrhages, vitreous hemorrhage, fibrovascular proliferation, and tractional retinal detachment (Figures 2 and 3).
Another more subtle sign is the lack or resolution of previously noted common diabetic retinopathy findings such as microaneurysms, intraretinal hemorrhage (dot/blot), and cotton-wool spots (Figure 4).
In the same fashion that a dried tree branch cannot bear any fruits, absence of capillary beds will result in resolution and/or absence of typical retinopathy. With increased capillary loss, the typical retinal features may disappear leading to a “featureless retina.”
On optical coherence tomography (OCT), disorganization and atrophic loss of inner-retinal layers, such as RNFL, ganglion cell, inner plexiform, and inner nuclear layers as these retinal structures are mainly supplied by the superficial and deep retinal vascular plexus (Figure 6).
The most effective technique for detecting retinal ischemia is studying the actual vessels. This is accomplished by retinal angiography via use of contrast dye, fluorescein sodium (FA) (Figures 5 and 6) and/or the newer technique known as optical coherence tomography angiography (OCTA; Figure 7).
There is no specific treatment for loss of retinal vasculature. The best approach is prevention by improved glycemic control as well as improvement of other comorbidities, such as systemic hypertension and hyperlipidemia. There are some suggestions that use of intravitreal anti-VEGF can reverse capillary nonperfusion in its early stages;2 however, advanced cases are irreversible.
In examination of patients with diabetes, ODs need to be in search of tell-tale signs of retinal ischemia and its complications and pursue appropriate management to reduce vision loss and prevent diabetic blindness.
1. Ozaki H, Yu AY, Della N, Ozaki K, Luna JD, Yamada H, Hackett SF, Okamoto N, Zack DJ, Semenza GL, Campochiaro PA. Hypoxia inducible factor-1alpha increased in ischemic retina: temporal and spatial correlation with VEGF expression. Invest Ophthalmol Vis Sci. 1999 Jan;40(1):182-9.
2. Shruti C, Sheth J, Anantharaman G, Gopalakrishnan M. Ranibizumab-induced retinal reperfusion and regression of neovascularization in diabetic retinopathy: An angiographic illustration. Am J Ophthalmol Case Rep. 2018 Jan 4;9:41-44.