At issue: PGA effect on SLT

Limited and potentially conflicting information from mechanistic and clinical studies provides fuel for a debate over whether prostaglandin analogue (PGA) use affects outcomes of selective laser trabeculoplasty (SLT).

Dr Francis rationalized that use of PGAs in eyes that have SLT is appropriate because the two modalities are traditionally thought to reduce IOP via complementary mechanisms - SLT by increasing aqueous outflow facility through the trabecular meshwork, and PGAs by increasing uveoscleral outflow.

Dr Francis also noted that the exact mechanism of action of SLT has yet to be elucidated, and he acknowledged there is evidence indicating overlap in the mechanism of action of SLT and PGAs.

"I was unable to find any published clinical data showing PGA treatment decreases the efficacy of SLT, and I will still use PGAs in conjunction with SLT," said Dr Francis, associate professor of ophthalmology and holder of the Ralph and Angelyn Riffenburgh Professorship in Glaucoma, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, USA. "However, further study is needed on this topic, including prospective clinical trials."

Some theories on the mechanism by which SLT increases outflow facility are based on the idea that the procedure produces inflammation, resulting in upregulation of cytokines that might activate macrophages and subsequently phagocytosis of cellular debris in the intertrabecular spaces, or induce a chemical signalling pathway that alters the cytoskeletal structure of the trabecular meshwork. In addition, there is evidence that the increase in outflow after SLT may be mediated by alteration of the meshwork's glycoproteome.

However, findings from a recent in vitro study performed by Alvarado and colleagues¹ showing that SLT and PGAs had similar effects on increasing permeability of cultured Schlemm's canal endothelial cells suggest these modalities may share a common mechanism of action and that their effects would be mutually exclusive of one other, Dr Francis said.

The clinical studies he reviewed that have investigated whether PGA treatment affects IOP lowering after SLT included a paper by Martow and colleagues,² who analysed a variety of factors as potential predictors of SLT and found adjunctive medical therapy had no effect on the procedure's success. Dr. Francis also cited a retrospective study by Singh et al.³ who found no difference in the 6-month SLT success rate comparing patients using and not using a PGA.

In addition, he reported the findings from a subgroup analysis of his own study (in press) designed to investigate the success of repeat SLT in patients who initially had successful IOP lowering for at least 1 year after a 360° primary SLT procedure. With patients categorized based on medication therapy, success rates by Kaplan-Meier survival analysis were similar among patients receiving PGAs and those taking aqueous suppressants, Dr Francis noted.