This lecture covers the basics of the initial Laser in Glaucoma and ocular HyperTension (LiGHT) Study publication as well as two follow up studies with important clinically relevant information.
Speaker: Dr. Malik Y. Kahook, Professor of Ophthalmology, University of Colorado, USA
Dr. Kahook: This is Malik Kahook from The University of Colorado and this is the second edition of one slide in 5 minutes. The topic today involves the elevation of primary Selective Laser Trabeculoplasty, or SLT, from a “side consideration” to a therapeutic approach that is much more common. The Laser in Glaucoma and ocular HyperTension Study, also known as the LiGHT Study, recruited consecutive, newly referred patients who were identified at six hospitals across the UK between 2012, and 2014. The study duration was 36 months.
Eligible patients had newly diagnosed, untreated open angle glaucoma (including a small number of pseudoexfoliation patients) or ocular hypertension in one or both eyes. Humphrey Visual Field (HVF) mean deviation requirement was no worse than –12 dB in the better eye or –15 dB in the worse eye and corresponding damage to the optic nerve. Patients were 18 years of age or older with visual acuity of 6/36 (20/120) or better in the eyes to be treated. Pervious ocular surgery was an exclusion, except uncomplicated phacoemulsification performed a year or more before randomization. Exclusion criteria also included contraindications to SLT (for example if the patients were unable to sit at the slit-lamp mounted laser, any past history of uveitis, or poor view of TM on gonioscopy), if they were unable to instill eye drops, had visually significant cataract, or those being treated for any ophthalmic condition.
It is important to note that clinicians and patients were not masked to the specific treatment arm. This was done in part to minimize the risk of the patient being less adherent to future drop use if they had received SLT initially and might believe they didn’t need to use drops. However, all measurements influencing treatment decisions (including visual field, optic disc imaging, and intraocular pressure measurements) were made by clinicians masked to treatment allocation. In cases where both eyes in the same patient were eligible, treatment was identical for both eyes. In both groups, patient mean age was ~62-63years, most patients were Caucasian (68-71%), most eyes where phakic and only a small subset of the OAG patient had Pseudoexfoliation –12 Meds (1.9%) 5 SLT (0.8%). Of note, pigmentary glaucoma patients were not included.
IOP goal was determined from both a percentage reduction (20% or 30% depending on disease status) from a single untreated baseline measurement (OHTS also used a single untreated baseline measurement but, unlike OHTS, the LiGHT study did not have any IOP eligibility criteria for enrollment, a strategy that can minimize Regression to the Mean).
Treatment escalation occurred if there was: (1) strong evidence of disease progression independent of intraocular pressure, (2) IOP above the target by more than 4 mm Hg at a single visit, or (3) IOP above the target by less than 4 mm Hg and less strong evidence of progression. Target IOP was decreased by 20% if disease progression was identified despite the measured IOP being at or below the set target level.
In the case of IOP above target by less than 4 mm Hg and no evidence of deterioration, the target IOP was revised to the mean of the previous three visits over which deterioration had not occurred. While this might seem a bit confusing… it is the way I practice in every day patient care. We are constantly revisiting our goal IOP based on specific clinical information as we engage with patients in clinic.
SLT treatment was completed over 360° of the trabecular meshwork using 100 non-overlapping shots (25 per quadrant), with the laser energy ranging between 0.3 to 1.4 mJ. Laser energy was to be titrated to observation cavitation bubbles and then the energy was decreased until bubbles were barely observable at least 50% of the time.
Re-treatment with SLT was allowed once if the initial treatment was noted to result in some lowering of IOP after the initial treatment. The next escalation was medical therapy for the SLT group. Repeat SLT was not done if the patient experienced complications from the initial treatment (ex. a spike in IOP). For the medical therapy arm, first line was prostaglandin analogues, second line was a blocker, third or fourth line was topical carbonic anhydrase inhibitors and alpha agonists. Systemic carbonic anhydrase inhibitors were only permitted while awaiting surgery. The study did not use SLT treatment for the drop arm prior to performing glaucoma surgery once maximum tolerated medical therapy was unsuccessful. Back to this point in a bit.
Data for the primary outcome were available for 652 (91%) of 718 patients at 36 months (92% of SLT group and 89% of the eye drops group) and were included in the intention-to-treat analysis.
Out of 718 patients, 517 (72.0%) were eligible in both eyes and 201 patients (28%) had only one eye eligible.
Overall 95% of eyes treated with SLT were at target IOP at 36 months. Target IOP was achieved without IOP medication in 78.2% of the eyes treated in the SLT group; of these 76.6% required only one treatment. A total of 74.2% of the patients in the SLT group were not using any drops at the 36-month visit. In comparison, 93.1% of the eyes treated in the eye drops group were at target IOP at 36 months, and 64.6% of patients were only using one medication.
Thirty-six eyes in the eye drops group had disease deterioration with three eyes converting from ocular hypertension to OAG and 33 eyes showing progression of OAG. In the SLT group, 23 eyes had disease deterioration with two eyes converting from ocular hypertension to OAG and 21 eyes showing progression of OAG. Cataract surgery was more common in the drop group (25) vs the drops group (13). The mean (SD) total power of initial SLT was 89.1mJ (+/-27.5) and the total number of applications was 98.9 (+/-4.6) shots.
Complications were minimal post SLT with one case of herpes simplex keratitis reactivation (also noted in one patient in the drops group) and two cases of uveitis (with one noted in the eye drops group). Only one eye required treatment due to IOP rise and resolved quickly with oral Acetazolamide.
One key finding was the requirement for glaucoma surgery (trabeculectomy) in 11 eyes (1.8%) in the eye drops group compared with none in the SLT group. Getting back to an earlier point, it is unclear how allowing SLT prior to surgery in the drops group might have influenced this, but my experience is that SLT does not perform as well in medicated eyes compared to treatment naïve eyes and the difference in surgery requirement remains significant in my mind despite this potential confounding issue.
Some other findings, from a cost perspective, SLT was found to be more cost effective than the drops first approach and took into consideration the cost of procedures, medications, follow-up visits and other parameters (non-eye related costs) that influence quality of life. There were more follow up visits in the SLT arm but there were more follow-up visits mandates in this group to be seen earlier post laser treatment.
There was a lack of quality of life differences between group which might be attributed to the type of questionnaire used with the focus more on the disease effect rather than the treatment effect and could be an area of further exploration in the future.
The authors concluded that primary SLT is a cost-effective alternative to drops that can be offered to patients with OAG or ocular hypertension needing treatment to lower IOP with the caveat that communication with the patient is key due to the possibility of some patients believing close monitoring is not necessary after laser (essentially fear that post laser patients might believe they are cured). My feeling is that adherence to follow up visits is poor across the board and not unique to patients post SLT compared to those receiving drops.
Two follow up LiGHT study publications are worth brief mention:
A study by Wright and colleagues looked at differences in VF progression (9 VFs over 48 months) between the two groups in the LiGHT study and found, using total deviation values, that 1 in 4 eyes in the medication group showed moderate or fast VF progression, whereas in the SLT group, this value was approximately 1 in 6. The authors concluded “With slower VF deterioration, SLT may delay or completely avert the need for more intense medical and surgical intervention in a significant proportion of patients.”
The second study by Garg and colleagues set to determine the efficacy of repeat SLT in the LiGHT study in patients requiring repeat treatment for early to medium-term failure of initial SLT treatment. 115 eyes of 90 patients received repeat SLT during the first 18 months of the study. Kaplan-Meier analysis of initial SLT survival demonstrated a median duration of effect of 189 days. Median duration of survival post repeat SLT could not be determined because 50% of these eyes did not reach the end point within the 18-month follow-up period, although available data show that median duration of survival in this group was at least 18 months. The Pre-treatment IOP before initial SLT was significantly higher than that before repeat SLT. A total of 34 eyes were early failures (retreated at 2 months after initial SLT) and 81 were considered late failures (retreatment after 2 months from initial SLT). The authors concluded that repeat SLT maintained drop-free IOP control in 67% of 115 eyes at 18 months. This is strong evidence that repeat SLT should be considered much earlier than would I would have considered in the past and that outcomes post repeat SLT can be clinically meaningful as well as long lasting and may obviate the need for adding drops or needing surgery to lower IOP for an extended period of time.
I was able to join Gus Gazzard and a few other colleagues on webinar where we discussed the LiGHT trial findings and Dr. Gazzard summarized the take home points as follows:
• Laser 1st gave drop-free disease control in 74% of patients at 3 years with less surgery and lower cost
• SLT was safe
• Primary SLT was associated with less rapid progression of visual field loss
• Repeat SLT was at least as effective as initial SLT treatment
My personal conclusion is that I should be offering more primary SLT to treatment naïve patients compared to what I have done in the past and I would welcome future exploration of adding SLT vs medications in patients already on one or two drops when treatment escalation is needed.
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