Open-angle glaucoma (OAG) is managed primarily with topical medical therapy, with laser and surgical interventions reserved for those in whom medical therapy is ineffective, intolerable, or inappropriate. The effectiveness of medical therapy is limited by patient adherence with therapy; inadequate adherence has been extensively documented. Selective laser trabeculoplasty (SLT) has comparable efficacy to preferred first-line prostaglandin analogues, is very safe, and obviates the need for daily medical therapy in most patients when applied as primary therapy. A recent randomized trial demonstrated superior glaucoma outcomes (less progression, fewer surgeries required) in newly diagnosed OAG patients receiving primary SLT vs. medical therapy, providing the evidentiary basis for a paradigm shift that is already underway in which SLT supplants medical therapy as the preferred first-line treatment for OAG. SLT is largely performed as first described by its inventor; little exploration of dose-response has been undertaken. An intriguing data set from Italy (with significant weaknesses and limitations) suggests that low energy SLT repeated annually is far more effective than standard SLT repeated as needed when its effect wanes, in delaying or preventing the need for topical medical therapy. This finding is consistent with the limited data exploring the dose-response relationship between SLT and intraocular pressure (IOP) reduction. Further, it is biologically plausible that ongoing health maintenance of trabecular meshwork (TM) function with proactive annual low energy SLT would better preserve the TM's long-term health and function than a repeated cycle of SLT, progressive TM re-impairment by the glaucoma process, loss of IOP control, and repeat SLT. Our proposal describes a multi-center clinical trial to answer two key questions: 1) Is primary low energy SLT as effective as primary standard energy SLT in newly diagnosed and treatment-nave patients with mild-moderate OAH or high-risk ocular hypertension?; and 2) Does annual low energy repeat SLT more effectively delay or prevent the need for medical therapy compared to standard SLT repeated as needed when its effect wanes and IOP rises? Participants will be randomized to initial standard SLT or initial low energy SLT with the possibility of a single repeat SLT as needed in the first year of the study. The first primary outcome will be 12-month survival where failure represents the need for repeat SLT to achieve/maintain protocol-specified target IOP. At Month 12, all participants who remain medication-free will be re-randomized to undergo repeat SLT either as needed when IOP exceeds target IOP (at initially randomized energy) or to annual low energy SLT irrespective of IOP. The second primary outcome will be 42-month medication-free survival in subjects who were medication-free at Month 12. Our study seeks to clarify the optimal way to utilize SLT with the ultimate goal of maximizing long- term SLT responsiveness and medication-free survival. If successful, our results will shape the course of treatment for most newly diagnosed and treatment-nave patients with mild-moderate OAG or high-risk OHT.
If we validate an SLT treatment strategy that extends the duration of medication-free disease control, we move one step closer to the possibility of a drop-free lifetime for our patients. Delaying the need for medications by 3, or 5, or 7 years not only confers all the benefits of medication-freedom during this period (which will be all that many patients would need in their lifetimes)?it also allows time for development of safer and more effective drugs dosed infrequently via sustained-release delivery systems, as well as better surgical options, for patients whose lifespans exceed SLT responsiveness. Thus, a new treatment paradigm consisting of SLT, then sustained-release medications, then surgery, could offer the majority of glaucoma patients the very real possibility of a drop-free lifetime of therapy.