Imaging of aqueous outflow in health and glaucoma. Justifying the re-direction of aqueous

Abstract

A wave of less invasive surgical options that target or bypass the conventional aqueous outflow system has been incorporated into routine clinical practice to mitigate surgical risks associated with traditional glaucoma drainage surgery. A blanket surgical approach for open-angle glaucoma is unlikely to achieve the desired IOP reduction in an efficient or economical way. Developing a precise approach to selecting the most appropriate surgical tool for each patient is dependent upon understanding the complexities of the aqueous outflow system and how devices influence aqueous drainage. However, homoeostatic control of aqueous outflow in health and glaucoma remains poorly understood. Emerging imaging techniques have provided an opportunity to study aqueous outflow responses non-invasively in clinic settings. Haemoglobin Video Imaging (HVI) studies have demonstrated different patterns of aqueous outflow within the episcleral venous system in normal and glaucomatous eyes, as well as perioperatively after trabecular bypass surgery. Explanations for aqueous outflow patterns remain speculative until direct correlation with findings from Schlemm's canal and the trabecular meshwork are possible. The redirection of aqueous via targeted stent placement may only be justifiable once the role of the aqueous outflow system in IOP homoeostasis has been defined.

Fig. 1. Minimally invasive glaucoma surgery (MIGS).

A Examples of surgical devices used to reduce intraocular pressure. From top left to bottom right: iStent, iStent inject, Hydrus Microstent, iTrack, trabectome, TRAB 360, Kahook Dual Blade, CyPass Micro-stent (withdrawn from market), iStent Supra (not commercially available), XEN 45, PreserFlo Microshunt, MicroPulse G6 cyclophotocoagulation. B Diagrammatic representation of anatomical approaches to MIGS (GATT indicates gonioscopy-assisted transluminal trabeculotomy). Adapted diagrams reprinted from Gillmann K et al. [2] with permission from Wolters Kluwer Health, Inc.

Fig. 2. The method used to calculate aqueous column cross-sectional area.

A Diagrammatic representation of aqueous column measurement from light intensity transepts. B, C An aqueous vein is pictured with a linear transept cutting across the vessel. The transept and corresponding graph are generated by Image J software. The aqueous column diameter equals the distance between the troughs (vertical blue arrows). The diameter in pixels is converted to aqueous column cross-sectional area (AqCA) in micrometres squared. Reproduced from Lusthaus et al. [31].

Fig. 3. Improvement of aqueous outflow following trabecular bypass surgery as evidenced by gradual aqueous column cross-section area (AqCA) increase during the first 3 months after surgery.

Linear transept is the site where AqCA measurement was taken. 0 = Preoperative laminar flow. AqCA increases 1 week after trabecular bypass surgery and this is maintained after 4 and 12 weeks. Adapted image reprinted from Lusthaus JA et al. [15] with permission from Wolters Kluwer Health, Inc.

Fig. 4. Gradual improvement in aqueous column cross-sectional area (AqCA) following trabecular bypass surgery after 4 weeks (N = 14; P = 0.002), 3 months (N = 10; P < 0.05) and 6 months (N = 9; P < 0.05).

Black lines represent median AqCA. Figure reprinted from Lusthaus JA et al. [15] with permission from Wolters Kluwer Health, Inc.

Fig. 5. Aqueous outflow after standalone TBS seems to reduce 1 day after surgery (D1), begins to recover after 1 week when a 38% IOP spike developed (W1), and then improves after 4 weeks (W4).

The white arrow in the preoperative image (0) represents the direction of aqueous drainage away from the limbus. AqCA reduces after surgery and then exceeds the preoperative measurement after 4 weeks. AqCA indicates aqueous column cross-sectional area, IOP intraocular pressure, TBS trabecular bypass surgery. Figure reprinted from Lusthaus JA et al. [16] with permission from Wolters Kluwer Health, Inc.

Fig. 6. A Mean percentage change in intraocular pressure (IOP) during the water drinking test. Peak IOP was seen 30 min after water ingestion in both groups.

A Mean percentage change in intraocular pressure (IOP) during the water drinking test. Peak IOP was seen 30 min after water ingestion in both groups. B The median percentage change in aqueous column cross-sectional area (AqCA) was compared at every interval. A poorly sustained AqCA response was seen in glaucomatous eyes with AqCA falling below baseline levels at 60 min. Adapted figures reprinted from Lusthaus JA et al. [37].

Fig. 7. Aqueous column widening occurs within an episcleral vein of a glaucomatous eye 15 min after water ingestion.

The aqueous column then reduces in size, almost disappears at 45 min and is not able to be detected after 60 min (not pictured). The site of aqueous column cross-section measurement is represented by a linear transept and the black arrows indicate direction of aqueous flow. Figure reprinted from Lusthaus JA et al. [37] with permission from Wolters Kluwer Health, Inc.