Tien Yin Wong

Whether the increase in vascular disease prevalence and mortality in OA populations is a result of co-occurrence of cardiovascular disease and OA, which are both common in the older population, is due to OA treatments or to the common association with reduced physical activity and/or obesity is unclear. One way to explore this non-invasively is to examine the cross-sectional relationship between changes in retinal microvasculature, which have been shown to be markers of generalized vascular pathology, and knee structural changes in an asymptomatic community-based population.

Background and Purpose—: Small-vessel disease contributes to the pathophysiology of stroke, and retinal microvascular signs have been linked to the risk of stroke. We examined the relationship of retinal signs with incident stroke in a multiethnic cohort. Methods—: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study that enrolled participants without clinical cardiovascular diseases from 6 US communities between 2000 and 2002. Of the participants, 4849 (71.2%) had fundus photography performed in 2002 to 2004. Retinopathy and retinal vessel caliber were assessed from retinal images. Stroke risk factors including high-sensitivity C-reactive protein, carotid artery intima-media thickness, and coronary artery calcium were measured using standardized protocols. Incident stroke was confirmed from medical record review and death certificates. Results—: After 6 years of follow-up, there were 62 incident strokes. Narrower retinal arteriolar caliber was associated with increased risk of stroke after adjusting for conventional cardiovascular risk factors (adjusted incidence rate ratio, 2.83; 95% CI, 1.34—5.95; P =0.006; adjusted hazard ratio, 3.01; 95% CI, 1.29–6.99; P =0.011). Retinopathy in persons without diabetes was associated with increased risk of stroke (adjusted adjusted incidence rate ratio, 2.96; 95% CI, 1.50–5.84; P =0.002; adjusted hazard ratio, 3.07; 95% CI, 1.17–8.09; P =0.023). These associations remained significant after adjusting for high-sensitivity C-reactive protein, carotid intima-media thickness, or coronary artery calcium. Conclusions—: Narrower retinal arteriolar caliber and retinopathy in nondiabetic persons were associated with increased risk of stroke in this relatively healthy multiethnic cohort independent of traditional risk factors and measures of atherosclerosis. The association between narrower retinal arteriolar caliber and stroke warrants further investigation.

Human Molecular Genetics 2012 21:2; pp. 437–445; doi: 10.1093/hmg/ddr463

To assess retinal vascular calibre changes in eyes with neovascular age-related macular degeneration (AMD), treated with intravitreal anti-vascular endothelial growth factor agents, over a 1-year period and compare any such changes to untreated fellow eyes. Treatment naïve patients with neovascular AMD received three consecutive intravitreal injections of ranibizumab, followed by a pro re nata dosing regimen up to 1 year, with the aim of maintaining a ‘fluid-free’ macula. Retinal arteriolar and venular calibre was measured from digital fundus photographs at baseline and at three monthly intervals to 1 year, and summarised as central retinal artery equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively. A total of 53 injected eyes and 41 fellow, non-injected eyes were analysed. At baseline, there were no differences in retinal vascular calibre between injected and non-injected eyes (mean CRAE (SD) 144.93 (14.07) vs 145.74 (13.10) μm, P=0.80 and mean CRVE (SD) 216.23 (25.93) vs 219.91 (22.82) μm, P=0.53). Over a 12-month period, retinal venular calibre dilatation occurred in injected eyes (mean CRVE change +5.71 (14.71) μm, P=0.007), with no change in retinal arterioles, +0.69 (14.71) μm, P=0.68. In non-injected eyes, arteriolar narrowing occurred as a whole, mean CRAE change −4.20 (7.00) μm, P=0.001, over 12 months, with a trend for narrowing in venules, −2.16 (11.56) μm, P=0.28. In injected eyes, after controlling for covariates, the changes in CRVE over 12 months mirrored improvements in macular thickness, −0.06 (−0.005, −0.11) μm, P=0.04, and visual acuity, +9.66 (−0.30, +19.32) μm, P=0.06. Intravitreal ranibizumab significantly dilated retinal venules after a 1-year period.

Background: To describe the changes in retinal vascular calibre in response to intravitreal ranibizumab injections in patients with neovascular age-related macular degeneration. Design: Prospective interventional case series. Participants: Treatment naïve patients with neovascular age-related macular degeneration were recruited over a 1-year period. Methods: Each patient received three monthly intravitreal injections according to a ‘loading dose’. Retinal arteriolar and venular calibre was measured from digital fundus photographs and summarized as central retinal artery equivalent and central retinal vein equivalent at baseline and 3 months. Main Outcome Measure: Central retinal artery equivalent and central retinal vein equivalent changes from baseline to 3 months. Results: Seventy-four eyes of 71 patients had good quality images for grading vessel calibre at baseline and at 3 months in treated (study) eyes and 51 eyes of 51 patients had good quality images in fellow (control) eyes. Over 3 months, in study eyes treated with ranibizumab, there was a significant increase in central retinal vein equivalent over baseline (+6.20 µm, P = 0.005), but no significant change in central retinal artery equivalent (+0.86 µm, P = 0.55). In control eyes, there was no change in central retinal vein equivalent (−0.82 µm, P = 0.70) or central retinal artery equivalent (0.34 µm, P = 0.75). Conclusion: Intravitreal ranibizumab has a significant vasodilational effect on retinal venular calibre in eyes treated for neovascular age-related macular degeneration. The reason for this change is unclear, but may relate to changes in blood flow or inflammatory changes within the retina.

OBJECTIVE: Endothelial dysfunction has been hypothesized as a possible pathogenic factor in the development of diabetic retinopathy (DR). We examined the relationship of DR to endothelium-dependent and endothelium-independent responses in skin microvascular flow. RESEARCH DESIGN AND METHODS: Participants consisted of 224 individuals with diabetes: 85 with type 1 diabetes and 139 with type 2 diabetes. Sodium nitroprusside (SNP) and acetylcholine (ACh) were delivered across the skin by iontophoresis. Laser Doppler flowmetry was used to assess the skin microcirculation response to SNP (endothelium-independent response) and ACh (endothelium-dependent response). The presence and severity of DR were graded from retinal photographs using a standard protocol. RESULTS: Of 224 participants, 64.3% had DR. After multivariable adjustment, participants with reduced responses to SNP or ACh were more likely to have DR, with an odds ratio (OR) of 2.33 (95% CI 1.09–5.01) for SNP and 2.20 (1.05–4.61) for ACh, comparing participants with responses below and above the median values. Participants with reduced responses (below the median) to both SNP and ACh were nearly four times more likely to have DR (OR 3.86 [1.45–10.3]) than those with SNP and ACh both above the median values. CONCLUSIONS: The presence of DR was associated with a reduction in skin microcirculation responses to iontophoresis of both SNP and ACh, suggesting that vascular processes associated with both endothelial dysfunction and endothelial function-independent mechanisms may be pathogenically related to DR.