Topical treatment for 1 week with latanoprost but not diclofenac reduces the diameter of dilated retinal arterioles in patients with type 1 diabetes mellitus and mild retinopathy

Abstract

ABSTRACT.Purpose: Diabetic retinopathy is characterised by morphological lesions secondary to retinal vascular impairment, and it is assumed that changes in the diameter regulation of retinal arterioles are involved in the disease pathogenesis. It has previously been shown that prostaglandin F2a can constrict retinal arterioles in vitro. In the present study, we investigated whether a similar effect could be achieved by topical administration in diabetic patients with dilated retinal arterioles and retinopathy. Methods: Twenty-two type 1 diabetic patients with mild retinopathy and twenty-four matched normal controls were randomized to topical treatment with the prostaglandin F2a agonist latanoprost twice daily for 1 week, followed by similar treatment with the cyclo-oxygenase inhibitor diclofenac, or to receive the two medications in the reverse order. The Dynamic Vessel Analyzer was used to assess the effect of the interventions on the resting diameter of retinal vessels and on the diameter response of retinal arterioles to increased blood pressure (BP) induced by isometric exercise and flicker stimulation. Results: Latanoprost reduced the resting diameter of retinal arterioles significantly in patients with diabetes (p = 0.01), but had no effect on normal persons. Diclofenac had no effect on the resting diameter of arterioles in either of the groups. The diameter responses to increased BP and flicker stimulation were not significantly changed by any of the treatments. Conclusion: Long-term prospective studies are needed to study the effect of topical treatment with latanoprost on the consequences of retinal hyperperfusion in retinal vascular diseases such as diabetic retinopathy.

Preserved Pressure Autoregulation but Disturbed Cyclo-Oxygenase and Nitric Oxide Effects on Retinal Arterioles during Acute Hypoxia in Diabetic Patients without Retinopathy

“…A recent in vitro study has shown that hypoxia-induced vasodilation depends on inducible NO in the perivascular retina [25], and supports the existence of an interaction between these two signaling pathways in vivo. The diameter responses during simultaneous flicker stimulation and isometric exercise were similar to those observed during flicker stimulation alone, which confirmed that metabolic autoregulation can overrule pressure autoregulation in order to adapt the blood flow to changes in retinal metabolism [28,30]. …”

“…The flicker-induced vasodilatation in the studied diabetic patients without retinopathy was reduced similarly to observations from diabetic patients [26,27,28,29,30], and during hypoxia the response was reduced further than in normal persons subjected to similar experimental conditions as in the present study [11]. L -NMMA has previously been found to increase flicker-induced dilatation of retinal vessels in normal persons [10] but had no significant effect in the studied diabetic patients without retinopathy.…”

The diameter response of retinal arterioles in diabetic maculopathy is reduced during hypoxia and is unaffected by the inhibition of cyclo-oxygenase and nitric oxide synthesis

“…The lack of contraction of retinal arterioles during isometric exercise explains why diclofenac was unable to affect this contraction during hypoxia, as has been shown previously in normal persons and in diabetic patients with minimal retinopathy during normoxia [31,38], and therefore the modulating effects of COX inhibition on retinal blood flow can be assumed to be less relevant in patients with diabetic maculopathy.…”

Impaired retinal vasodilator responses in prediabetes and type 2 diabetes

“…In addition, retinal attenuation further increased with the progression of diabetic retinopathy (Mandecka et al. 2007; Tilma & Bek 2012). Retinal vascular dysfunction is proposed to contribute to the pathogenesis of diabetic retinopathy (Schmetterer & Wolzt 1999), but the exact microvascular changes that precede diabetes are not clearly understood (Caballero 2005).…”