Subha T. Venkataraman

Vascular Reactivity of Optic Nerve Head and Retinal Blood Vessels in Glaucoma—A Review

Please cite this paper as: Venkataraman, Flanagan and Hudson (2010). Vascular Reactivity of Optic Nerve Head and Retinal Blood Vessels in Glaucoma—A Review. Microcirculation17(7), 568–581.

Retinal arteriolar and capillary vascular reactivity in response to isoxic hypercapnia.

The aim of the study was to compare the magnitude of vascular reactivity of the retinal arterioles in terms of percentage change to that of the retinal capillaries using a novel, standardized methodology to provoke isoxic hypercapnia. Ten healthy subjects (mean age 25 years, range 21-31) were recruited. Subjects attended a single visit comprising two study sessions separated by 30 min. Subjects were fitted with a sequential re-breathing circuit connected to a computer-controlled gas blender. Each session consisted of breathing at rest for 10 min (baseline), increase of P(ET)CO(2) (maximum partial pressure of CO(2) during expiration) by 15% above baseline whilst maintaining isoxia for 20 min, and returning to baseline conditions for 10 min. Retinal hemodynamic measurements were performed using the Canon Laser Blood Flowmeter and the Heidelberg Retina Flowmeter in random order across sessions. Retinal arteriolar diameter, blood velocity and flow increased by 3.3%, 16.9% and 24.9% (p<0.001), respectively, during isoxic hypercapnia. There was also an increase of capillary blood flow of 34.8%, 21.6%, 24.9% (p< or =0.006) at the optic nerve head neuroretinal rim, nasal macula and fovea, respectively. The coefficient of repeatability (COR) was 5% of the average P(ET)CO(2) both at baseline and during isoxic hypercapnia and was 10% and 7% of the average P(ET)O(2) (minimum partial pressure of oxygen at end exhalation), respectively. The overall magnitude of retinal capillary vascular reactivity was equivalent to the arteriolar vascular reactivity with respect to percentage change of flow. The magnitude of isoxic hypercapnia was repeatable.

Retinal Arteriolar Vascular Reactivity in Untreated and Progressive Primary Open-Angle Glaucoma

Purpose. To determine (1) the magnitude of retinal arteriolar vascular reactivity to normoxic hypercapnia in patients with untreated primary open-angle glaucoma (uPOAG) or progressive (p)POAG and in control subjects and (2) the effect of treatment with 2% dorzolamide on retinal vascular reactivity in uPOAG. Methods. The sample comprised 11 patients with uPOAG (after undergoing treatment, they became treated (t)POAG), 17 patients with pPOAG (i.e., manifesting optic disc hemorrhage), and 17 age-similar control subjects. The partial pressure of end-tidal CO(2) (PetCO(2)) was stabilized at 38 mm Hg at baseline. After baseline (10 minutes), normoxic hypercapnia was then induced (15 minutes) with an automated gas flow controller. Retinal arteriolar and optic nerve head (ONH) blood hemodynamics were assessed. The procedures were repeated after treatment with 2% dorzolamide for 2 weeks in tPOAG. Results. Baseline arteriolar hemodynamics were not different across the groups. In control subjects, diameter, velocity, and flow increased (P < 0.001) in response to normoxic hypercapnia. There was no change in all three hemodynamic parameters to normoxic hypercapnia in uPOAG, whereas only blood flow increased (P = 0.030) in pPOAG. Vascular reactivity was decreased in uPOAG and pPOAG patients compared with that in control subjects. After treatment with topical 2% dorzolamide for 2 weeks, the tPOAG group showed an increase in diameter, velocity, and flow (P </= 0.04) in response to normoxic hypercapnia. Similar trends were noted for ONH vascular reactivity. Conclusions. A reduced magnitude of arteriolar vascular reactivity in response to normoxic hypercapnia was shown in uPOAG and in pPOAG. Vascular reactivity improved after dorzolamide treatment in POAG.

The relationship between retinal vascular reactivity and arteriolar diameter in response to metabolic provocation.

PURPOSE To compare the magnitude of vascular reactivity in response to metabolic provocation in retinal arterioles of varying diameter in healthy young subjects. METHODS Ten healthy young subjects (26.2 +/- 3.5 years [mean +/- SD]) attended for three sessions. Session 1 was used to select two discrete hemodynamic measurement sites along the superior temporal arteriole. Retinal arteriolar blood flow was assessed at relatively narrow and wide sites. At sessions 2 and 3, CO(2) and O(2) were sequentially administered (and alternated across sessions) using manual gas flow control via a modified sequential rebreathing circuit to achieve target hypercapnia and hyperoxia. Blood flow was assessed for each gas phase. Total vascular reactivity capacity (TVRC) was taken as the difference in flow between hypercapnia and hyperoxia. RESULTS The baseline diameter for the narrow and wide measurement sites was 92.4 microm (+/-13.6) and 116.7 microm (+/-12.7), respectively (ReANOVA; P < 0.0001). Hyperoxia induced a decrease in blood flow, whereas hypercapnia increased flow (P < 0.0001). TVRC was greater for the wide than for the narrow measurement sites (Delta flow narrow = 3.0 microL/min versus Delta flow wide = 6.6 microL/min; P < 0.0001). In terms of percentage change in flow relative to baseline, TVRC was the same between the wide and narrow sites (Delta narrow = 67% versus Delta wide = 61%; P > 0.05). CONCLUSIONS In response to metabolic provocation, absolute TVRC was greater for retinal arteriolar measurement sites with wider baseline vessel diameters. However, percentage change in retinal blood flow was the same irrespective of initial arteriolar diameter.

Impact of simulated light scatter on scanning laser Doppler flowmetry.

Aim: To determine the impact of simulated light scatter on scanning laser Doppler flowmetry (SLDF) assessment of retinal capillary blood flow and retinal image quality. Methods: One eye of 10 normal subjects (mean (SD) age 24 (1.7) years, range 22–27) was randomly selected. Varying concentrations of polystyrene microspheres were suspended in optically clear cells to simulate light scatter. The microsphere concentrations used were 0.05%, 0.03%, 0.02%, 0.01%, and a cell containing only water. LogMAR visual acuity and contrast sensitivity were measured both with and without cells. Optimal focus and alignment was established by acquiring three SLDF images each of the optic nerve head (ONH) and of the macula using the Heidelberg retina flowmeter (HRF) with no cell in place. SLDF images were subsequently acquired with each of the light scatter cells mounted in front of the HRF. The group mean retinal capillary blood flow was compared using repeated measures analysis of variance (reANOVA) as a function of microsphere concentration. Results: Retinal capillary blood flow increased significantly in the ONH, nasal macula, fovea, and temporal macula with increasing microsphere concentration (p<0.0001). Using Dunnett’s post hoc test, retinal capillary blood flow was found to be significantly increased relative to the no cell condition for the 0.03% and 0.05% cell concentrations. Conclusions: Simulated light scatter produces an artifactual increase in retinal capillary blood flow. The impact of cataract on SLDF measurements has yet to be determined.

The impact of artificial light scatter on scanning laser tomography.

Purpose. The impact of cataract (which frequently occurs alongside glaucoma) on scanning laser tomography (SLT) is poorly understood. The aim of this pilot study was to determine the impact of artificial light scatter on SLT estimates of optic nerve head (ONH) topography. Methods. The sample comprised 10 healthy, young subjects of mean age 23.5 years. One eye of each subject was randomly selected. Cells filled with increasing concentrations of 0.50-&mgr;m diameter polystyrene microspheres were prepared. The cells were mounted in front of the objective lens of the Heidelberg Retina Tomograph (HRT) II and were tilted at an angle of 20° to eradicate any surface reflections. Three sets of ONH scans were initially acquired without any light scatter cell in place and then three further sets were acquired for each of four different concentrations of microspheres in a randomized order. The impact of artificial light scatter on cup-to-disc area ratio, cup volume, rim volume, cup shape measure, height variation contour, and mean retinal nerve fiber layer (RNFL) thickness was evaluated. Results. Repeated-measures analysis of variance showed that there was no significant change in cup-to-disc area ratio, cup volume, rim volume, height variation contour, cup shape measure, or mean RNFL thickness as a function of increasing light scatter cell concentration. Conclusion. Artificial light scatter had no statistically significant impact on the stereometric parameters of the HRT II. From a clinical perspective, useful SLT data can be acquired with confidence from patients with diagnosed/suspected glaucoma and concomitant cataract.