This study adhered to the tenets of the Declaration of Helsinki. Informed patient consent and approval by the Institutional Review Board of The Hospital Authority of Hong Kong were obtained prior to study commencement. The authors declare no financial or conflicting interests.
The study was registered with the following publicly accessible registries: the Clinical Trials Register of the University of Hong Kong (trial registration number: HKCTR1847) in April 2012 and retrospectively registered with the European Clinical Trials Database (trial registration number: 2014-003305-15) on August 11, 2014.
The methodology of this study has been previously described in parts . This was a prospective cohort study from July 2012 to March 2014, conducted at a university hospital in Hong Kong.
The study recruited cases of unilateral or bilateral NTG subjects who were currently on topical anti-glaucoma medications. NTG was defined by open angle on gonioscopy, glaucomatous visual field loss on Humphrey visual field analyzer as per the Hodapp-Parrish-Anderson’s criteria , progressive thinning of the retinal nerve fiber layer on Optical Coherence Tomography, and Goldmann applanation measured IOP < 21 mmHg on all documented clinical visits. Cases were excluded if they had received prior surgery or laser for the treatment of glaucoma or taking any systemic medications that may affect IOP. Patients were also excluded if there were contraindications for SLT like corneal pathologies or scars; they did not complete follow-up visits to12 months, or if any intraocular surgery or repeated SLT was performed within 12 months of the first SLT treatment.
The pre-study IOP with anti-glaucoma medication and the number of anti-glaucoma medication used were recorded prior to study enrollment. Fixed combination eye drops were counted as two types of anti-glaucoma medication. All patients then underwent a 1-month washout period where all anti-glaucoma medications were discontinued. A mean baseline IOP without medication was then calculated after IOP phasing at 9 am, 1 pm, and 5 pm. An individual target IOP was calculated as a 30% reduction from the baseline IOP, as per the findings from The Collaborative Normal Tension Glaucoma Study .
All patients received a single session of SLT using a Q-switched Nd:YAG laser (Ellex Solo™, Ellex Medical Pty. Ltd., 82 Gilbert Street, Adelaide, SA 5000 Australia) with an initial energy of 0.8 mJ. The power was titrated up or down until bubble formation was just visible. A single glaucoma specialist (JWYL) delivered the SLT treatment and both eyes were treated in the same laser session for those with bilateral disease. In all treated eyes, a single drop of Brimonidine Tartrate (Alphagan P, Allergan Inc., Waco Texas, United States of America) was instilled immediately after SLT. Dexamethasone 0.1% and Neomycin 0.5% combination eye drop (Dexoptic-N by Ashford Laboratories Pvt. Ltd., 31/36, 5th Floor, Dheeraj Heritage,S. V. Road, Santacruz West, Mumbai - 400 054, India) was used twice daily for 1 day and was continued for a few more days only if anterior chamber reaction was seen on day 1 after SLT. Subjects returned for follow-up on day 1, 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months after SLT. At 1 month after SLT, IOP phasing (9 am, 1 pm, and 5 pm) was repeated and a mean 1-month IOP was calculated. IOP phasing was only performed before and at 1-month after SLT. Anti-glaucoma medications were resumed and titrated based on clinical response to achieve the preset target IOP for each individual. The order of resuming anti-glaucoma medication included the following: first, alpha-adrenergic agonists or prostaglandin analogues were prescribed followed by topical carbonic anhydrase inhibitors and then lastly, β-blockers. This order was based on the understanding from the Low-pressure Glaucoma Treatment Study that NTG subjects treated with alpha-adrenergic agonists were less likely (9.1%) to develop visual field progression than those using β-blockers (39.2%) . When multiple medications were required, fixed combination medications were given to simplify the drug regimen.
The primary outcome measure included IOP at the following time intervals: pre-study with medication, baseline phasing after washout, 1 day, 1 week, 1 month post-SLT phasing, without medication, 3 months, 6 months, 9 months, and 12 months after SLT.
The secondary outcomes included these: the number of anti-glaucoma medications used pre-study and again at 3 months, 6 months, and 12 months after SLT. Goldmann applanation tonometry was used to measure IOP.
Definitions of success
Absolute success: IOP reduction ≥ 20% after SLT compared to baseline without any additional anti-glaucoma medication
Qualified success: IOP reduction ≥ 20% reduction compared to baseline, with additional anti-glaucoma medication
Only the right eye was used for statistical analysis. The Friedman test with Dunn’s Multiple Comparison posthoc test was used to calculate the following outcome measures over the study period:
IOP at pre-study and at 1 day, 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months post-SLT.
Number of anti-glaucoma eye drops at pre-study and 1 month, 3 months, 6 months, and 12 months post-SLT.
A Kaplan-Meier survival curve was used to represent the “mortality” after SLT, which was defined as the need of a repeated SLT procedure during the study period.
All means were expressed as mean ± standard deviation. Statistical significance was defined as P < 0.05.