Nailfold Capillary Abnormalities in Primary Open-Angle Glaucoma: A Multisite Study

Abstract

PURPOSE. There is considerable evidence for systemic vascular dysfunction in primary openangle glaucoma (POAG). We performed nailfold capillary video microscopy to observe directly the nature of nonocular microvasculature abnormalities in POAG. METHODS.We enrolled 199 POAG patients and 124 control subjects from four sites. We used JH-1004 capillaroscopes to perform nailfold capillary video microscopy on the fourth and fifth digits of each subject's nondominant hand. Videos were evaluated for hemorrhages, dilated capillary loops > 50 lm, and avascular zones > 100 lm by graders masked to case status. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for POAG were obtained by means of logistic regression analyses that were applied to data from all cases and controls. Corresponding estimates of moderate or severe POAG versus mild POAG (based on the Hodapp-Anderson-Parrish scale) were obtained among cases only. RESULTS.After controlling for demographic factors, family history of glaucoma, systemic diseases, and use of anticoagulation and antiplatelet therapy, for each 100 nailfold capillaries assessed, all types of microvascular abnormalities were significantly associated with POAG. Specifically, the presence of any dilated capillaries (OR ¼ 2.9; 95% CI, 1.6-5.6), avascular zones (OR ¼ 4.4; 95% CI, 1.7-11.3) and hemorrhages (OR ¼ 12.2; 95% CI, 5.9-25.1) were associated with POAG. Among cases, the frequency of microvascular abnormalities was not associated with glaucoma severity (P ‡ 0.43).CONCLUSIONS. These data provided support for nonocular capillary bed abnormalities in POAG. Comparable vascular abnormalities in the optic nerve may render it susceptible to glaucomatous damage.

Nailfold capillary morphology in exfoliation syndrome

“…Previously we reported that 76.9% of 199 POAG patients had any hemorrhages using a protocol identical to the one used for this work. 21 Using an entirely new patient sample we observed that 71.3% of POAG patients had similar findings. In contrast, 60.8% of XFS/XFG had any hemorrhages.…”

“…We speculated that impaired nitric oxide signaling might be responsible for nailfold hemorrhages in POAG. 21 Interestingly, some 51,52 but not all studies 53 show that asymmetric dimethyl arginine, an inhibitor of nitric oxide synthase and contributor to endothelial cell dysfunction, is elevated in the aqueous humor and serum of XFS/XFG patients. One needs also to consider that other mechanisms may be operative in the formation of nailfold hemorrhages in XFS/XFG including a tendency for inherent blood clot formation as demonstrated by rotational thromboelastography.…”

“…Nailfold capillary videomicroscopy is used for diagnostic purposes in rheumatology 19 and has served a role in defining vascular changes in primary open-angle glaucoma (POAG). [20][21][22] Although nailfold capillary hemodynamics in XFS have been assessed, 16 the nailfold capillary morphology in XFS/XFG has never been studied. The nailfold capillary bed shares the same hairpin loop architecture as the iris microvasculature 23,24 and thus may serve as a useful surrogate to gain further insight into the systemic manifestations of XFS/XFG.…”

Relating glaucomatous visual field loss to retinal oxygen delivery and metabolism

“…Pasquale et al. () studied the relationship between nailfold microvascular abnormalities and POAG. In that study, investigators found a 12‐fold increased risk of POAG in association with nailfold haemorrhages indicating systemic vascular abnormalities.…”

“…; Pasquale et al. ). Specifically, reductions in retinal, choroidal and retrobulbar blood flow and impairment in vascular autoregulation (Flammer et al.…”