CHAPTER 43 Laser trabeculoplasty
Introduction
In 1974, Worthen and Wickham first described a laser procedure for the treatment of open angle glaucoma (OAG)1. The laser was directed at the trabecular meshwork and they believed the procedure to be a trabeculotomy. Soon thereafter, Krasnov demonstrated a decrease in intraocular pressure (IOP) using a Q-switched laser to perform ‘goniopuncture’2. In 1979, Wise and Witter introduced the technique and parameters for an enduring procedure called argon laser trabeculoplasty (ALT)3. Since then, different techniques such as trabeculopuncture have been tried with limited long-term success. Interestingly, laser irradiation of the trabecular meshwork (TM) with the neodymium : YAG laser (1064 nm), diode laser (810 nm), and krypton laser (red 647.1 nm or yellow 568.2 nm) also reduce IOP comparably with ALT. Since these lasers interact with the TM in different ways, it suggests the hypotensive effect of laser trabeculoplasty (LTP) is multifactorial. In 1998, Latina published a pilot study using a Q-switched 532-nm Nd : YAG laser to perform trabeculoplasty that lowered IOP without causing coagulative damage to the TM4. This method was coined ‘selective laser trabeculoplasty’ (SLT). SLT and ALT have become the two most common forms of LTP performed for OAG and will be the focus of this chapter.
Epidemiology
The Early Manifest Glaucoma Trial was the first large randomized clinical trial to show that reduction of IOP with a combination of a beta blocker and ALT can slow disease progression in patients with manifest OAG5. Lowering IOP, medically or with laser or filtration surgery, remains the only viable approach to favorably alter the course of OAG. Therefore, the focus of glaucoma treatment remains centered on IOP control at an estimated cost of $623–2511 per patient per year in 20046. In the US, the direct medical cost of glaucoma, including medical treatment, surgical procedures and outpatient visits, was $2.86 billion in 2004. Medical therapy accounts for 38–52% of direct costs7. While real world data on the cost effectiveness of LTP are lacking, studies using simulated models that make assumptions about treatment efficacy suggest that LTP lowers yearly treatment costs for OAG. In one study, the cumulative 5-year cost of treatment with medication alone was $6571, while treatment with LTP reduced the cost to $4838, (including the cost of the procedure), therefore offering a 5-year saving of $1733 or a yearly savings of $346 per patient8. Clinically, the Glaucoma Laser Trial showed that initial treatment with ALT was as effective as initial treatment with topical medication9. Therefore, the use of LTP as treatment, compared with topical medications or in conjunction with medications, may be a reasonable option for selected OAG patients. Using a Medicare database, the numbers of LTPs peaked in 1992 with 176 670 procedures performed10. LTP numbers declined steadily until 2002, when the rates started to increase again to 169 680 in 20067. Given the trend of increased use, along with data regarding clinical efficacy and favorable economic impact, we need to review our understanding of the fundamental principles and describe the techniques of ALT and SLT.
Fundamental principles
The mechanisms of action of ALT and SLT are not completely understood, but are thought to be different from one another. A comparison of the morphological changes in the TM of eight human eye bank eyes after these procedures offers some insight. After ALT, scanning electron microscopy (SEM) revealed crater formation in the treated areas, measuring approximately 70 µm. Coagulative damage was evident along the base and edges of the craters, with disruption of the collagen scaffolding and scattered debris derived from disrupted trabecular beams. Intracellular changes were evaluated with transmission electron microscopy (TEM). TEM also revealed disrupted trabecular endothelial cells with coagulative damage. In contrast, evaluation with SEM of eyes treated with SLT revealed no evidence of crater formation or coagulative damage. There was minimal evidence of mechanical change, with only rare crack-like defects of the corneo-scleral meshwork identifiable. TEM revealed no coagulative damage to trabecular cells, but revealed disrupted intra-cytoplasmic pigment granules within pigmented TM endothelial cells11. See Figure 43.1.
Postulated mechanisms of action of ALT include: mechanical, cellular, and biochemical. The mechanical theory suggests that coagulative damage causes shortening or ‘tightening’ of the inner trabecular lamellae. This trabecular tightening may increase outflow by preventing trabecular beams from collapsing. In 1972, Nesterov performed perfusion studies on 20 cadaver eyes and proposed that collapse of the trabecular lamellae upon each other and onto Schlemm’s canal may contribute to primary open angle glaucoma (POAG)12. Thus, the mechanical theory of ALT proposes that the tightening of the trabecular lamellae prevents or delays collapse of the lamellae or Schlemm’s canal allowing for increased outflow. The efficacy of a new procedure, canaloplasty, provides some construct validity for the mechanical theory of ALT. In canaloplasty, a 10-0 suture is threaded into Schlemm’s canal for 360° and a knot is tied to tighten the trabecular ring. This vaults Schlemm’s canal inwards and in one study the degree of this effect was proportional to the magnitude of IOP lowering13. The mechanical theory explains IOP lowering based on changes in anatomic conformations.
The cellular theory, or the ‘repopulation’ theory, suggests that LTP stimulates TM cell division and repopulates the trabecular beams with healthy cells that contribute to an improved outflow facility. In support, a histological study that measured TM cellularity in patients with POAG compared with that of non-glaucomatous individuals found that the TM from POAG patients had lower cellularity than age-matched normals14. Laser may stimulate repopulation by cells that are derived from a stem cell population in the anterior, non-filtering region of the TM15. LTP may also trigger macrophage infiltration of the TM aiding removal of cellular debris and thereby increase outflow facility16.
The cellular theory links to the biochemical theory due to the altered biochemical profile of healthier cells that repopulate the TM. Furthermore, infiltrating macrophages may also degrade extracellular matrix, further improving outflow facility. The biochemical theory focuses primarily on the alterations in the extracellular matrix, particularly the juxtacanalicular tissue, which allows aqueous to enter Schlemm’s canal. Such changes are of particular interest for the mechanism of SLT, since SLT produces minimal mechanical and coagulative changes in the TM, yet results in a significant IOP lowering effect. The trabecular surface and intratrabecular spaces are lined with mucinous glycosaminoglycans (GAGs). GAGs are important contributors to aqueous outflow resistance in the juxtacanalicular connective tissue and regulate fluid outflow by forming gel-like solutions. Laser treatment has been shown to alter the expression of GAGs by the TM cells17. Whether the modulation GAGs directly changes the extracellular matrix to allow for more outflow, or if it allows the TM cells to respond to biophysical cues and further modulate the matrix to then increase outflow, is yet to be elucidated18,19. Studies of other factors released by the TM that regulate Schlemm’s canal permeability are also contributing to the understanding of the mechanisms of LTP. SLT results in the release of interleukin-1α, 1β, and tumor necrosis factor-α into the aqueous humor. These cytokines bind to TM cells near the juxtacanalicular tissue and increase flow across the extracellular matrix tissues by inducing the release of matrix metalloproteinases19. Therefore, the IOP lowering effect is not due to one factor but likely due to the interactions of many mechanisms and enzyme cascades.
Preoperative assessment
Determining which patients are good candidates for LTP requires assessment of multiple factors. These include age, race, angle anatomy, TM pigmentation, and the mechanism of glaucoma. Some secondary glaucomas such as pigmentary20, exfoliative21, or steroid-induced22 can be treated successfully with LTP, while others such as uveitic, angle-recession23, and those associated with irido-corneal endothelial syndrome show minimal benefit with LTP. Congenital or juvenile glaucomas or glaucomas associated with angle dysgenesis and malformations also do not respond well to LTP.
Preoperative gonioscopy is essential when LTP is considered as a treatment modality. This not only determines the status of the angle structures but allows assessment patient cooperation as well, since the procedure will require adequate intraoperative patient positioning and lens placement. Anecdotally, we have found that patients with severe blepharospasm and small lid fissures may require a pediatric Goldmann lens for successful LTP. It is advantageous to recognize such challenges preoperatively rather than in the laser suite. During gonioscopy note the amount of TM pigmentation, as this dictates the power necessary at the time of LTP. For both ALT and SLT, increased pigmentation likely leads to increased absorption of laser energy by pigmented TM cells. Eyes with increased TM pigmentation are at higher risk of post-LTP IOP spikes (particularly SLT24
