At the moment, two classes of glaucoma surgeries have been gaining favor among cataract and glaucoma surgeons: gonioscopy-assisted transluminal trabeculotomy (GATT) and ab-interno trabeculotomy (AIT). They are currently popular among eye surgeons as these procedures require minimal additional training or skill, are fast to perform, reimburse well, and appear to be modestly effective at lowering intraocular pressure (IOP). Both GATT and AIT work through similar mechanisms: GATT involves tearing through the trabecular meshwork whereas with AIT a strip of trabecular meshwork is removed. However, mounting evidence suggests that we should be sparing, not tearing the trabecular meshwork.
Before addressing the reason we should consider protecting the trabecular meshwork, it is helpful to understand why we would wish to destroy this tissue in the first place. The trabecular meshwork has traditionally been viewed as a type of microscopic drainage grate within the eye. Fluid within the eye (aqueous fluid) must pass through this grate in order to leave the eye, similar to how excess rain water must pass through a grate in the street. Just as street drains can get clogged by leaves and other debris, the trabecular meshwork is prone to getting clogged in those with glaucoma.
It has widely been believed that a clogged trabecular meshwork was the main problem in glaucoma. This was first proposed in the late 19th century (Leber, 1873). Apparent proof of this was provided almost a century later by Dr. W. Morton Grant (Grant, 1958, 1963). However, we now know that Grant’s work failed to take into account multiple important physiologic components affecting IOP. Grant himself later concluded that there is actually little resistance in the TM itself (Ellingsen and Grant, 1971a, 1971b, 1972; Johnstone and Grant, 1973a, 1973b; Van Buskirk and Grant, 1973, 1974). Despite this, the idea that the primary problem in glaucoma was from resistance to flow at the trabecular meshwork has ossified into near dogma among ophthalmologists.
If one believes that the trabecular meshwork is essentially obstructing the drainage of fluid within the eye, then it makes intuitive sense to remove what is blocking the exit. Shortly after Dr. Grant’s 1958 publication, “Nylon filament trabeculotomy in glaucoma” was described in which a suture was threaded into Schlemm’s canal and then ripped through the trabecular meshwork. (Smith, 1962). This was the precursor to modern GATT surgery which is a minimally invasive (MIGS) modification of Nylon filament trabeculotomy that was first described in 2014 (Grover et al., 2014)
There is a problem with Nylon filament trabeculotomy and GATT, however. Our bodies have inherent systems to heal damage caused by trauma. Just as a cut in our skin tends to heal leaving a small scar, so would the tear in the trabecular meshwork scar down over time, essentially undoing the effect of the surgery (Wada et al., 1994). In order to address this issue a new surgery, ab-interno trabeculotomy (AIT), was developed. In this surgery a specialized instrument was used to remove (rather than just tear) a strip of trabecular meshwork from the eye. In theory this would make it much harder for the body to seal up the opening created during surgery.
If Grant’s initial conclusion that the majority of the resistance to outflow was at the trabecular meshwork, then removing the trabecular meshwork should have resulted in intraocular pressures (IOPs) near what is called the episcleral venous pressure (EVP, 7-8mmHg). This is a range of IOP which most glaucoma surgeons would consider to be ideal for those with glaucoma. However, AIT tended to lower the IOP only into the high teens, over twice as high as the EVP. Why wasn’t this working as intended?
We now know that over half of the resistance to outflow is located “distal to” (beyond) the trabecular meshwork. Assuming the outflow system is just a series of restrictions to flow, removing the trabecular meshwork is simply insufficient to lower IOP below the teens. However, even this understanding to the outflow system is grossly simplified and outdated.
Recent discoveries have demonstrated that the conventional outflow system is anything but passive. Indeed, rather than just blocking outflow, the trabecular meshwork acts as a critical component of a complex system of active pumping of aqueous fluid (Johnstone, 2004). To clarify, modern understanding suggests that the trabecular meshwork functions as a piston that pushes aqueous fluid out of Schlemm’s canal into even smaller tubes (the collector channels). If this piston is destroyed, so is the pump. It doesn’t take an engineer to understand that if a pump is malfunctioning the solution is to fix the pump, not destroy it. Yet, destroying the pump is exactly what is being done with GATT and AIT.
Some surgeons might argue that, “Well, we don’t know how to fix it, so we might as well do what we can.” This might be a reasonable argument if pumping was the only function of the trabecular meshwork . However, we now also know that in addition to pumping fluid out of the eye, the trabecular meshwork acts as both a sensor of pressure and regulator of aqueous outflow.
As such the healthy trabecular meshwork doesn’t just restrict outflow but monitors, controls, and facilitates it as well (Johnstone et al., 2020).
Given this modern understanding, tearing through or removing the trabecular meshwork not only destroys the pump, but breaks the control system used by the eye to monitor and regulate the drainage of fluid out of the eye.
If your home is too warm on a summer day and your air conditioner is not keeping up would you “solve” this problem by opening up your windows, smashing the air conditioner, and ripping the control box off of the wall? Of course not. Yet, this is what we are essentially doing to the complex and active system of IOP control in the eye when either GATT or AIT are performed. Granted, if the system is so irreversibly broken that it cannot be fixed then you may have no other option than to just open the windows. Likewise, there are times when there may be no other reasonable option to “fix” or restore function to the eye’s drainage system.
However, just because we do not currently have methods of restoring the function of the natural outflow system in the eye, it is potentially unwise to destroy it. You would likely still enjoy some relief from the heat even with a poorly functioning air conditioner and would not, therefore, intentionally break it. We need to consider the possibility that the trabecular meshwork (even when damaged in glaucoma) is still at least partially functioning and that we should try to preserve this remaining function, not destroy it.
Unfortunately, we currently do not have any method of assessing what active control and pumping functions may still be present in the trabecular meshwork of someone with glaucoma. This, however, is likely to change as imaging systems that are currently available only in research labs are made available to clinicians and their patients. Indeed, based on this imaging research we now know that the pumping function (though decreased) is still active in at least some patients with glaucoma (Gao et al., 2020).
There are other reasons to spare the trabecular meshwork as well. The newest class of glaucoma medications (the ROCK-NET inhibitors) work on the trabecular meshwork and there is evidence that this class of medications can actually restore some of the lost function. If the trabecular meshwork is destroyed then this class of medication will not be an option for those patients who have undergone GATT or AIT.
Finally, there is a strong tradition among glaucoma surgeons that has existed for over half a century dictating that eye tissue that may be needed for potential future surgery should be “spared“. This tradition is based on the understanding that glaucoma is a chronic, progressive disease that has no cure.
Although not appreciated by many individuals with glaucoma, one surgery is seldom enough to maintain IOP control for life.
As such, it is important to avoid damaging or destroying tissue that may be needed for future surgical treatments. In the past, that tissue was the conjunctiva which was needed for successful trabeculectomy surgery. This admonition to spare conjunctiva was so strong that it bordered on unethical to even make a small cut in this tissue in patients who might someday require trabeculectomy.
Surgeons that commonly perform GATT or AIT may reasonably argue that we do not have available surgical treatments capable of restoring trabecular meshwork function, so there is no great need to spare this tissue. That argument ignores the fact that we already have a medical treatment (netarsudil) capable of restoring some function. It is also pessimistic with regard to how quickly strides are being made in this area. There are currently multiple academic and commercial institutions that are actively developing pharmaceutical and surgical treatments targeted toward enhancing the active outflow system (most of which would require an intact trabecular meshwork). It’s not outside of the realm of possibility to think that one of these treatments could be available as an effective treatment for glaucoma sometime over the next five years. If so, doesn’t it make sense to protect the trabecular meshwork in the hope that it can be fixed at some date in the future?
Medicine, like all fields, is subject to trends and fads. Although many eye surgeons have chosen to jump onto the current GATT and AIT glaucoma treatment trends, it’s important to reflect on how what is done today may be regretted in the future. I, for one, regret wearing 1970s clothing styles whenever I come across family pictures of my childhood.
When concerning treatment of a potentially blinding disease, however, the cost of engaging in a fad is not just a tinge of embarrassment, but sight itself.
We should, therefore, keep in mind the wisdom of those glaucoma specialists who have lived through many treatment fads of the past, and spare the tissues that we may need to protect our patients from future loss of vision. As we enthusiastically embrace the “new” (GATT, AIT) we must not forget or toss aside the wisdom we have gained from the older methods of treating glaucoma.
References:
Ellingsen, B.A., Grant, W.M., 1971a. Influence of intraocular pressure and trabeculotomy on aqueous outflow in enucleated monkey eyes. Invest. Ophthalmol. 10, 705–709.
Ellingsen, B.A., Grant, W.M., 1971b. The relationship of pressure and aqueous outflow in enucleated human eyes. Invest. Ophthalmol. 10, 430–437.
Ellingsen, B.A., Grant, W.M., 1972. Trabeculotomy and sinusotomy in enucleated human eyes. Invest. Ophthalmol. 11, 21–28.
Gao K, Song S, Johnstone MA, et al., 2020. Reduced Pulsatile Trabecular Meshwork Motion in Eyes With Primary Open Angle Glaucoma Using Phase-Sensitive Optical Coherence Tomography. Investigative Ophthalmology & Visual Science. 61(14):21-21. doi:[10.1167/iovs.61.14.21](https://doi.org/10.1167/iovs.61.14.21)
Grant, W.M., 1958. Further studies on facility of flow through the trabecular meshwork. Arch. Ophthalmol. 60, 523–533.
Grant, W.M., 1963. Experimental aqueous perfusion in enucleated human eyes. Arch. Ophthalmol. 69, 783–801.
Grover DS, Godfrey DG, Smith O, Feuer WJ, Montes de Oca I, Fellman RL. Gonioscopy-assisted transluminal trabeculotomy, ab interno trabeculotomy: technique report and preliminary results, 2014. Ophthalmology. 121(4):855–61. https://doi.org/10.1016/j.ophtha.2013.11.001
Johnstone, M.A., Grant, W.M., 1973a. Pressure-dependent changes in structure of the aqueous outflow system in human and monkey eyes. Am. J. Ophthalmol. 75, 365–383.
Johnstone, M.A., Grant, W.M., 1973b. Microsurgery of schlemm’s canal and the human aqueous outflow system. Am. J. Ophthalmol. 76, 906–917.
Johnstone MA, 2004. The Aqueous Outflow System as a Mechanical Pump: Evidence from Examination of Tissue and Aqueous Movement in Human and Non-Human Primates. Journal of Glaucoma. (5):421-438. doi:10.1097/01.ijg.0000131757.63542.24
Johnstone M, Xin C, Tan J, Martin E, Wen J, Wang RK, 2020. Aqueous outflow regulation – 21st century concepts. Progress in Retinal and Eye Research. (Published online November 17, 2020):100917.
Leber, T., 1873. Studien über den flüssigkeitswechsel im auge. Albr. v. Gr. Arch Ophthal. 19, 87–106.
Smith R., 1962. Nylon filament trabeculotomy in glaucoma. Trans Ophthalmol Soc U K. 82:439-454.
Van Buskirk, E.M., Grant, W.M., 1973. Lens depression and aqueous outflow in enucleated primate eyes. Am. J. Ophthalmol. 76, 632–640.
Van Buskirk, E.M., Grant, W.M., 1974. Influence of temperature and the question of involvement of cellular metabolism in aqueous outflow. Am. J. Ophthalmol. 77, 565–572.
Wada Y, Nakatsu A, Kondo T, 1994. Long-term results of trabeculotomy ab externo. Ophthalmic Surg. 25(5):317-320.
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David Richardson, MD
Medical Director, San Marino Eye
David Richardson, M.D. is recognized as one of the top cataract and glaucoma surgeons in the US and is among an elite group of glaucoma surgeons in the country performing the highly specialized canaloplasty procedure. Morever, Dr. Richardson is one of only a few surgeons in the greater Los Angeles area that performs MicroPulse P3™ "Cyclophotocoagulation" (MP3) glaucoma laser surgery. Dr. Richardson graduated Magna Cum Laude from the University of Southern California and earned his Medical Degree from Harvard Medical School. He completed his ophthalmology residency at the LAC+USC Medical Center/ Doheny Eye Institute. Dr. Richardson is also an Ambassador of Glaucoma Research Foundation.
