Hemoglobin Video Imaging Detects Differences in Aqueous Outflow Between Eyes With and Without Glaucoma During the Water Drinking Test.

PRCIS: Hemoglobin video imaging (HVI) demonstrates increased aqueous outflow (AO) in response to the water drinking test (WDT) in patients with and without glaucoma. In glaucomatous eyes, increased AO was not sustained, and characteristic flow patterns were seen. PURPOSE: To observe how variations in intraocular pressure (IOP) correlate with the flow of aqueous in episcleral veins. DESIGN: Prospective observational cohort study. PARTICIPANTS: The WDT increased AO into the episcleral venous system in 30 eyes recruited from Sydney Eye Hospital. A comparison was made between glaucomatous (n=20) and nonglaucomatous eyes (n=10). METHODS: Each patient had baseline IOP and HVI before drinking 10 mL/kg body weight of water. IOP and HVI were then repeated every 15 minutes for 1 hour. Aqueous column cross-sectional area (AqCA) of the most prominent nasal and temporal aqueous veins was used to semi-quantify conventional AO. MAIN OUTCOME MEASURES: Change in IOP and AqCA from baseline during the WDT. Aqueous flow characteristics were also observed. RESULTS: Peak IOP elevation above baseline was significantly higher in the glaucoma group, with an average IOP rise of 39.7% on 1.6 1.1 medications, compared with 22.9% in the control group ( P =0.04). AqCA significantly increased for glaucomatous and nonglaucomatous eyes in response to water ingestion ( P <0.05). AqCA fell by 50% in glaucomatous eyes ( P =0.003) and 33% in nonglaucomatous eyes ( P =0.08) at study completion compared with the peak measurement. IOP remained >30% elevated in 8 glaucomatous eyes (40%) after 60 minutes and no control eyes. Variations in qualitative aqueous flow patterns were observed in glaucomatous eyes but not in controls. CONCLUSIONS: AO volume, estimated by AqCA, increases in response to IOP elevation induced by an ingested water bolus in patients with and without glaucoma. The increase in aqueous drainage was not sustained in glaucomatous eyes and may have led to incomplete recovery of IOP. Using HVI in combination with the WDT may assist with clinical decision-making and facilitate the monitoring of responses to treatment.

Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition-Induced Hypertension: The HYPAZ Trial.

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Aqueous outflow imaging techniques and what they tell us about intraocular pressure regulation.

Recent advances in the medical and surgical management of open-angle glaucoma have increased the number of treatment options available. Several new intraocular pressure (IOP)-lowering treatments target the conventional aqueous outflow (AO) system. However, success rates are variable and outcomes in individual patients are often difficult to predict. Variable treatment responses remain unexplained and highlight deficiencies in our current understanding of AO regulation and IOP homeostasis. Imaging is often relied upon to confirm diagnoses and monitor treatment responses in other ocular and systemic pathologies. As yet no suitable AO imaging tool has been developed to fulfil this role in glaucoma. A variety of imaging techniques have been used to study the AO tracts of humans and animals in ex vivo and in vivo eyes. In this review, results from novel imaging techniques that assess aqueous drainage through the episcleral venous system are considered and we argue these provide new insights into AO regulation. We suggest that the ability to objectively measure AO responses to interventions would be a significant clinical advance, and we have demonstrated that this can be achieved with direct visualisation of aqueous drainage. We predict that the evolution of AO imaging technology will continue to reveal critical components of AO and IOP regulation, and that personalised IOP-lowering treatment in glaucoma care may well become a reality in the near future.

The Effects of Trabecular Bypass Surgery on Conventional Aqueous Outflow, Visualized by Hemoglobin Video Imaging.

PRECIS: Hemoglobin Video Imaging (HVI) provides a noninvasive method to quantify aqueous outflow (AO) perioperatively. Trabecular bypass surgery (TBS) is able to improve, and in some cases re-establish, conventional AO. PURPOSE: The purpose of this study was to use HVI to illustrate and quantify effects of TBS on AO through the episcleral venous system. DESIGN: This is a prospective observational cohort study. PARTICIPANTS: Patients were recruited from Sydney Eye Hospital, Australia. The study included 29 eyes from 25 patients, 15 with glaucoma and 14 normal controls. TBS (iStent Inject) was performed on 14 glaucomatous eyes (9 combined phacoemulsification/TBS and 5 standalone TBS). Cataract surgery alone was performed on the remaining eye from the glaucoma group and 2 eyes from the control group. METHODS: We used HVI, a novel clinic-based tool, to visualize and quantify AO perioperatively during routine follow-up to 6 months. Angiographic blood flow patterns were observed within prominent aqueous veins on the nasal and temporal ocular surface. Aqueous column cross-section area (AqCA) was compared before and after surgery. MAIN OUTCOME MEASURES: AqCA, number of aqueous veins, intraocular pressure (IOP) before and after surgery, and number of IOP-lowering medications. RESULTS: Patients with glaucoma had reduced AqCA compared with normal controls (P=0.00001). TBS increased AqCA in 13 eyes at 1 month (n=14; P<0.002), suggesting improved AO. This effect was maintained at 6 months in 7 eyes (n=9, P≤0.05). All patients with unrecordable AO before surgery (n=3; 2 standalone TBS, 1 combined cataract/TBS) established measurable flow after TBS. IOP and/or medication burden became reduced in every patient undergoing TBS. Cataract surgery alone (n=3) increased AqCA in nasal and temporal vessels at 4 weeks after surgery. CONCLUSIONS: HVI provides a safe method for detecting and monitoring AO perioperatively in an outpatient setting. Improvement of AO into the episcleral venous system is expected after TBS and can be visualized with HVI. TBS is able to improve, and in some cases re-establish, conventional AO. Cataract surgery may augment this. Some aqueous veins were first seen after TBS and these patients had unstable postoperative IOP control, which possibly suggests reorganization of aqueous homeostatic mechanisms. HVI may confirm adequacy of surgery during short-term follow-up, but further work is required to assess the potential of HVI to predict surgical outcomes and assist with personalized treatment decisions.

Hemoglobin Video Imaging Provides Novel In Vivo High-Resolution Imaging and Quantification of Human Aqueous Outflow in Patients with Glaucoma.

Purpose: Noninvasive, detailed measurement of the dynamics of human aqueous outflow is difficult to achieve with currently available clinical tools. We used hemoglobin video imaging (HVI) to develop a technique to image and quantify human aqueous outflow noninvasively and in real time. Design: A prospective observational study to describe characteristics of aqueous veins and a pilot prospective interventional feasibility study to develop quantification parameters. Participants: Patients were recruited from the Cambridge University Hospitals NHS Foundation Trust Glaucoma clinic. The observational study included 30 eyes, and the pilot interventional feasibility study was performed on 8 eyes undergoing selective laser trabeculoplasty (SLT). Our SLT protocol also included the installation of pilocarpine and apraclonidine eye drops. Methods: Participants underwent HVI alongside their usual clinic visit. Main Outcome Measures: The change in cross-sectional area (CSA) of the aqueous column within episcleral veins was correlated with intraocular pressure (IOP) reduction and change in visual field mean deviation (MD) before and after intervention. Fluctuations in contrast and pixel intensity of red blood cells in an aqueous vein were calculated to compare the flow rate before and after intervention using autocorrelation analysis. Results: Hemoglobin video imaging enables the direct observation of aqueous flow into the vascular system. Aqueous is seen to centralize within a laminar venous column. Flow is pulsatile, and fluctuations of flow through globe pressure or compression of the aqueous vein are observed. There was a significant increase in the aqueous column after the administration of our SLT protocol (n = 13; P < 0.05). This correlated with the degree of IOP reduction (n = 13; Pearson's correlation coefficient 0.7; P = 0.007) and the improvement in MD observed postintervention (n = 8; Pearson's correlation coefficient 0.75; P = 0.03). Autocorrelation analysis demonstrated a faster rate of decay in an aqueous vein after intervention, indicating an increase in flow rate. Conclusions: Hemoglobin video imaging can be incorporated into a routine clinic slit-lamp examination to allow a detailed assessment and quantification of aqueous outflow in real time. It has the potential to be used to help target therapeutic interventions to improve aqueous outflow and further advance our understanding of aqueous outflow dysregulation in the pathogenesis of glaucoma.