It's all about the (aqueous) flow

When it comes to the treatment of glaucoma, there is growing evidence to suggest that the ability to re-establish the natural flow of aqueous humour plays a critical role not only in reducing IOP, but also in preserving the health of the corneal endothelium, says US ophthalmologist DR DAVID LUBECK.

In a healthy eye, most aqueous humour drains through the conventional outflow pathway, flowing from the anterior chamber through progressively smaller channels of the trabecular meshwork into Schlemm’s canal. From the canal, circuitous channels, known as collector channels, connect to the episcleral vasculature, which drains into the venous system. The flow of aqueous throughout the conventional outflow pathway is dynamic and is determined by intraocular pressure (IOP), outflow resistance or facility and episcleral venous pressure, and can be described as natural aqueous flow.

Blockages can occur along several points of the conventional outflow pathway, including the trabecular meshwork, Schlemm’s canal and the collector channels, disrupting the natural aqueous flow and resulting in elevated IOP. It also has the consequence of depriving the eye of the nutrient- rich flow of aqueous throughout the full 360 degrees of the conventional outflow pathway, thereby contributing to the pathogenesis of glaucoma.

While all MIGS devices aim to overcome the reduced outflow facility associated with glaucoma, their respective mechanisms of action are very different. Considering each of the MIGS devices, they are often categorised based on whether they require the use of a stent or implant. These microtrabecular bypass stents commonly include iStent (Glaukos) and Hydrus (Ivantis). There are also MIGS designed to remove or manipulate the trabecular meshwork tissue, referred to as goniotomy (KDB, New World Medical) or ab-interno trabeculotomy (OMNI, Sight Sciences).

The results of a prospective study presented at the 2021 meeting of the American Society of Cataract and Refractive Surgery (ASCRS) would posit another criterion for the categorisation of MIGS and glaucoma treatments: the re-establishment of natural aqueous flow, as compared to the creation of artificial flow.

Presented by doctors David M. Lubeck, MD, ABO and Robert J. Noecker, MD, MBA, ABO and awarded best paper in the session “Minimally Invasive Glaucoma Surgery (MIGS) II”, the 12-month data reported a mean change in endothelial cell density (ECD) of 3.2% (SD ±9.0%) following ab-interno canaloplasty (iTrack, Nova Eye Medical) performed in conjunction with cataract surgery – and represents one of the lowest reported rates of endothelial cell loss (ECL) of all the MIGS procedures. Refer to Table 1 below.

Table 1: A comparison of endothelial cell loss rates between the different MIGS procedures. References can be found at the bottom of this article.

At the ASCRS meeting, Lubeck asked the question of whether it is the change in aqueous currents which is responsible for much of the loss in ECD following glaucoma treatment.

“It is well accepted that more invasive glaucoma surgeries such as trabeculectomy and tube shunts are associated with a more significant loss of ECD² ,” he said.

“In the case of tube shunts, much of this loss is thought to result from the mechanical disruption caused by the shunt itself. Studies estimate ECL at between 8.0% and 18.6%^3-6 at two years for tube shunt surgery and between 9.5% and 28.0% at one year^7-10 for trabeculectomy.”

Examining the various MIGS procedures and their impact on the corneal endothelium, the reported rates of ECL are much lower than that of traditional glaucoma surgeries.

“Micro-trabecular bypass stents, when correctly implanted in the angle, should not negatively impact on the health of the corneal endothelium,” Lubeck said. “Further, migration of these stents is uncommon. They do create artificial flow, however, and the impact of this on the corneal endothelium may warrant further consideration. With MIGS procedures such as goniotomy, there is the additional drawback of post-operative inflammation that may disrupt the delicate environment of the corneal endothelium.”

He added: “In contrast, ab-interno canaloplasty re-establishes natural aqueous flow throughout the entire 360 degrees of the conventional outflow pathway without the use of an implant, and without the removal or damage of tissue. Theoretically it may safeguard against the risk of excessive damage to the corneal endothelium.”

During the ab-interno canaloplasty procedure, 360-degree catheterization and viscodilation dilates the canal and separates the compressed tissue planes of the trabecular meshwork. It also acts downstream on the collector channel ostia, pushing out herniations of trabecular meshwork tissue, which have been shown to block up to 90% of collector channels in glaucomatous eyes¹¹ .

“There is no denying the improved safety profile afforded by MIGS. I would encourage my peers to consider the impact of MIGS on natural aqueous flow, and how this relates to the health of the corneal endothelium.”

ABOUT THE AUTHOR: Dr David Lubeck is Assistant Clinical Professor of Ophthalmology, UIC Eye Center, Chicago; director of advanced anterior segment surgery, Arbor Centers for Eye Care, Homewood, Illinois. Financial disclosures: consultant/speaker (Alcon, Glaukos, Nova Eye Medical).

Article references

Goel M, Picciani RG, Lee RK and Bhattachary SK. Aqueous humor dynamics: a review. The Open Ophthalmology Journal, 2010; 4:52-59
Janson BJ, Alward WL, Kwon YH, et al. Glaucoma-associated corneal endothelial cell damage: A review. Surv Ophthalmol. 2018;63(4):500-506
Lee EK, Yun YJ, Lee EJ, et al. Changes in corneal endothelial cells after Ahmed glaucoma valve implantation: 2-year follow-up. Am J Ophthalmol. 2009;148(3):361-367.
Kim KN, Lee SB, Lee YH, et al. Changes in corneal endothelial cell density and the cumulative risk of corneal decompensation after Ahmed glaucoma valve implantation. Br J Ophthalmol. 2016;100(7):933-938.
Tan AN, Webers CA, Berendschot TT, et al. Corneal endothelial cell loss after Baerveldt glaucoma drainage device implantation in the anterior chamber. Acta Ophthalmol. 2017;95(1):91-96.
Tojo N, Hayashi A, Consolvo-Ueda T, et al. Baerveldt surgery outcomes: anterior chamber insertion versus vitreous cavity insertion [published online August 31, 2018]. Graefes Arch Clin Exp Ophthalmol. 2018;256(11):2191-2200.
Arnavielle S, Lafontaine PO, Bidot S, et al. Corneal endothelial cell changes after trabeculectomy and deep sclerectomy. J Glaucoma. 2007;16(3):324-328.
Nassiri N, Nassiri N, Rahnavardi M, et al. A comparison of corneal endothelial cell changes after 1-site and 2-site phacotrabeculectomy. Cornea. 2008;27(8):889-894.
Storr-Paulsen T, Norregaard JC, Ahmed S, et al. Corneal endothelial cell loss after mitomycin C-augmented trabeculectomy. J Glaucoma. 2008;17(8):654-657.
Konopińska J, Deniziak M, Saeed E, et al. Prospective randomized study comparing combined phaco-ExPress and phacotrabeculectomy in open angle glaucoma treatment: 12-month follow-up. J Ophthalmol. 2015;2015:720109
Cha ED, Xu J, Gong H. Variations in active areas of aqueous humor outflow through the trabecular outflow pathway. Presented at ARVO 2015.)

Table 1 references

Samuelson, T. W., Sarkisian, S. R., Jr, Lubeck, D. M., Stiles, M. C., Duh, Y. J., Romo, E. A., Giamporcaro, J. E., Hornbeak, D. M., Katz, L. J., & iStent inject Study Group (2019). Prospective, Randomized, Controlled Pivotal Trial of an Ab Interno Implanted Trabecular Micro-Bypass in Primary Open-Angle Glaucoma and Cataract: Two-Year Results. Ophthalmology, 126(6), 811–821https://doi.org/10.1016/j.ophtha.2019.03.006
Arriola-Villalobos, P., Martínez-de-la-Casa, J. M., Díaz-Valle, D., García-Vidal, S. E., Fernández-Pérez, C., García-Sánchez, J., & García-Feijoó, J. (2013). Mid-term evaluation of the new Glaukos iStent with phacoemulsification in coexistent open-angle glaucoma or ocular hypertension and cataract. British Journal of Ophthalmology, 97(10), 1250-1255.
Gillmann K, Mansouri K, Ambresin A, Bravetti GE, Mermoud A. A Prospective Analysis of iStent Inject Microstent Implantation: Surgical Outcomes, Endothelial Cell Density, and Device Position at 12 Months. J Glaucoma. 2020 Aug;29(8):639-647.
Samuelson, T. W., Chang, D. F., Marquis, R., Flowers, B., Lim, K. S., Ahmed, I. I. K., & Pfeiffer, N. (2019). A Schlemm canal microstent for intraocular pressure reduction in primary open-angle glaucoma and cataract: the HORIZON study. Ophthalmology, 126(1), 29-37.
M. Lubeck, MD, and R.J. Noecker, MD, unpublished data, 2021; accepted for presentation at ASCRS 2021).
Oddone, F., Roberti, G., Posarelli, C., Agnifili, L., Mastropasqua, L., Carnevale, C., … & Figus, M. (2021). Endothelial Cell Density After XEN Implant Surgery: Short-term Data From the Italian XEN Glaucoma Treatment Registry (XEN-GTR). Journal of Glaucoma, 30(7), 559-565.

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