During the past several years, prostaglandin medical therapy has become the standard first-line treatment for glaucoma worldwide. For that reason, it is important to evaluate concomitant prostaglandin therapy versus other antiglaucoma medications on the efficacy of SLT.
SLT AND TOPICAL DROPS
Dr. Latina and Vikas Gulati, MD, both from Boston, and John Dagianis, MD, of Nashua, New Hampshire, showed that SLT further lowers the IOPs of patients on topical glaucoma medications.2 The type of antiglaucoma medications may affect the degree of additional lowering with adjunctive SLT, however. This retrospective chart review compared 15 eyes on monotherapy with a prostaglandin analogue that underwent SLT (group 1) with 15 IOP-matched eyes on an aqueous suppressant (beta-blocker or carbonic anhydrase inhibitor) that underwent SLT (group 2) (Table 1). No changes were made to the type or frequency of topical drops for at least 1 month after SLT.
In group 1, SLT reduced subjects' IOPs from a baseline of 22.27 ±3.13 mm Hg to 18.15 ±3.38 mm Hg (an 18.02% reduction). In group 2, the IOP reduction was similar (not statistically significant, P=.39), decreasing from a baseline of 22.27 ±3.10 mm Hg to 17.21 ±2.80 mm Hg (a 22.11% reduction) (Figure 1). The response rate (IOP reduction > 3 mm Hg) was significantly lower in group 1 eyes (47%) as compared with group 2 eyes (87%) (Figure 2). These results suggest that the IOP reduction and the percentage response to SLT were better if eyes were concomitantly receiving aqueous suppressants versus prostaglandins.
Although baseline IOP can be a significant determinant of an eye's response to SLT, it does not entirely explain the better response rates in the aqueous suppressant group observed in this study (Table 2). If the IOP were greater than 21 mm Hg, the response rate for the aqueous suppressant group was two times higher than that for the prostaglandin group. Likewise, for baseline IOPs of less than 21 mm Hg, the response rate for the aqueous-suppressant group was also twice that of the prostaglandin group. The overall correlation between the baseline IOP and response of eyes on both drugs was 25% (Table 3), a finding suggesting that other factors are involved, including the effect of the drug itself and its combination with the SLT procedure.
PROSTAGLANDINS ARE OUTFLOW DRUGS
Prostaglandins are known to improve the uveoscleral outflow. Topical treatments with certain prostaglandins, including prostaglandin F2-alpha receptor agonists, lower IOP by increasing uveoscleral outflow. Although the precise mechanism for the increased uveoscleral outflow is not known, these agents appear to activate a molecular transduction cascade and an increase in the biosynthesis of certain metalloproteinases. These changes lead to a reduction in extracellular matrix components (collagen types I, III, and IV; laminin; fibronectin; and hyaluronans) within the ciliary muscle.3 This reduction of the extracellular matrix within portions of the uveoscleral pathway may contribute to the mechanism of increased uveoscleral outflow. Additional mechanisms that may contribute to the prostaglandin-mediated increase of uveoscleral outflow include relaxation of the ciliary muscle, changes in cell shape, cytoskeletal alteration, or compaction of the extracellular matrix within the tissues of the uveoscleral outflow pathway.
SLT AS AN OUTFLOW TREATMENT
The precise mechanism by which SLT lowers the IOP is still unknown. Alvarado et al4 suggested that macrophages play an important role. The investigators demonstrated an increase in growth factors and chemo-attractants such as tissue growth factor-beta, tissue necrosis factor, and interleukin-1 with SLT therapy. They theorized that SLT may also activate a prostaglandin pathway or a prostaglandin-like effect. Further, they proposed that injury to the pigmented trabecular meshwork cells after SLT results in the release of chemo-attractants that recruit monocytes, which are activated and transform into macrophages upon interacting with SLT-injured tissues. After these macrophages engulf and clear the pigment granules from the trabecular meshwork tissues, they exit the eye to return to the circulation via Schlemm's canal.4
That SLT selectively targets pigmented trabecular meshwork cells suggests that the treatment works at the cellular level, either (1) through migration and phagocytosis of trabecular meshwork debris by the macrophages or (2) by stimulating the formation of healthy trabecular tissue that may enhance the outflow properties of the trabecular meshwork. Both mechanisms could also influence and increase the aqueous flow through the uveoscleral pathway, as does topical prostaglandin therapy.
A reduction in IOP can occur through a variety of mechanisms (eg, decreased production of aqueous humor by the ciliary body and/or increased aqueous outflow through the trabecular meshwork and/or the uveoscleral pathway). The net reduction in IOP depends on the interaction of these individual mechanisms. Thus, if SLT lowers IOP through the trabecular meshwork and/or uveoscleral pathways, then it may not substantially enhance these drainage pathways when used as adjunctive therapy with prostaglandins. In contrast, if SLT affects trabecular meshwork and uveoscleral outflow, then the addition of an aqueous suppressant eye drop might enhance the procedure's IOP-lowering effect, because the aqueous suppressants would work through a different pressure-lowering mechanism. This reasoning might account for the greater response of eyes on aqueous suppressants that underwent SLT in the study by Latina et al.2
CONCLUSION
One should consider SLT to be an outflow therapy. The likelihood of an IOP-lowering response seems to be higher when SLT is combined with an inflow drug (eg, a beta-blocker or carbonic anhydrase inhibitor) versus an outflow drug (eg, a prostaglandin analogue). Prostaglandins may still be effective in conjunction with SLT, but the rate of nonresponders is greater. A large-scale, prospective study is needed to resolve and confirm the relationship between SLT and glaucoma medications.
John Mark S. de Leon, MD, is a glaucoma fellow, Massachusetts Eye and Ear Infirmary, Boston. He stated that he holds no financial interest in the product or in the company mentioned herein. Dr. de Leon may be reached at (781) 526-4110; jmarkmd@edsamail.com.ph.
Mark A. Latina, MD, is Associate Clinical Professor, Tufts University, Medford, Massachusetts. He stated that he holds a financial interest in Lumenis, Inc. Dr. Latina may be reached at (781) 942-9876; mark.latina2@verizon.net.
1. Melamed S, Simon GJB, Levkovitch-Verbin H. Selective laser trabeculoplasty as primary treatment for open-angle glaucoma. Arch Ophthalmol. 2003;121:957-960.
2. Latina MA, Gulati V, Dagianis J. IOP lowering effect of SLT may be influenced by the type of concomitant anti-glaucoma drops. Paper presented at: The AAO Annual Meeting; October 24, 2004; New Orleans, LA.
3. Ocklind A. Effect of latanoprost on the extracellular matrix of the ciliary muscle. A study on the cultured cells and tissue sections. Exp Eye Res. 1998;67:179-191.
4. Alvarado JA, Murphy CG. Outflow obstruction in pigmentary and primary open angle glaucoma. Arch Ophthalmol. 1992;110:1769-1778.
