At present, the only treatment for glaucoma is the reduction of intraocular pressure (IOP). Trabeculectomy is the most commonly performed surgical intervention and has been proven to be more effective than medications (drops) in achieving lower IOP. For this reason, clinical guidelines in the UK and Europe suggest that trabeculectomy be offered to patients with advanced glaucoma as the first line of treatment.
The Treatment of Advanced Glaucoma Study (TAGS) is a recently completed multicentre randomised controlled trial (RCT) comparing medical versus surgical (trabeculectomy) treatments in patients presenting with previously untreated advanced open angle glaucoma (OAG). The primary outcome was vision related quality of life (QoL) measured using the Visual Function Questionnaire 25 (VFQ-25). Recently reported results indicated no difference in this primary outcome between treatment arms for the period of the study (24 months). However, patient self-reported outcome measures have been shown to lack sensitivity in detecting visual deterioration from glaucoma.
Visual field (VF) tests are an important clinical measure in glaucoma and have been successfully used as a primary outcome in previous important glaucoma trials. In the primary report of results from TAGS, the average difference in VF mean deviation (MD) between baseline and 24 months showed no difference between the two groups, despite an average 3 mmHg difference in IOP favouring trabeculectomy. However, TAGS was designed such that series of 24-2 VFs (Humphrey Field Analyzer [HFA], Zeiss Meditec, Dublin, CA) were collected at baseline and 24 months; the main trial report did not take account of all these data.
In this study Giovanni Montesano et al conducted post-hoc analysis of VF data from a two-arm multicenter randomized controlled clinical trial. Authors applied these methods to the serial VF data from TAGs with the objective of identifying whether there is a treatment difference between the study arms not seen in the primary outcome to compare visual field (VF) progression between the two arms of the Treatment of Advanced Glaucoma Study (TAGS).
453 patients with newly diagnosed advanced open-angle glaucoma in at least one eye from 27 centers in the United Kingdom were randomized to either trabeculectomy (N = 227) or medications in their index eye (N = 226) and followed-up for two years with two 24-2 VF tests at baseline, 4, 12 and 24 months. Authors analyzed data for participants with a reliable VF (False positive rate < 15%) at baseline and at least two other time-points. Time for each eye to progress from baseline beyond specific cut-offs (0.5, 1, 1.5 and 2 dB) was compared using survival analysis.
211 eyes in the trabeculectomy-first arm and 203 eyes in the medications-first arm were analyzed. The average RoPs were -0.59 [-0.88, -0.31] dB/year in the medications-first arm and -0.40 [-0.67, -0.13] dB/year in the trabeculectomy-first arm. The difference was not significant (Bayesian p-value = 0.353). More eyes progressed in the medications first arm: ≥0.5 dB (p = 0.001), ≥1dB (p = 0.014), ≥1.5dB (p = 0.071) and ≥2dB (p = 0.061).
The main outcome did not show any statistically significant difference in the rate of VF progression in patients randomised to trabeculectomy first compared to medication first after 24 months of follow-up. Study also explored possible differences in localised progression, by analysing the average progression rate for different VF clusters, by comparing the RoP of the fastest cluster and the average RoP of the 5 fastest locations in each eye and, finally, by comparing the time to estimated perimetric blindness of individual locations. These comparisons all failed to reach significance. However, authors found a significantly higher percentage of eyes progressing beyond specific cut-offs from baseline sensitivity, indicating lower frequency of progressive VF loss in eyes receiving trabeculectomy first.
The authors concluded there was no significant difference in the average RoP at two years. Initial trabeculectomy significantly reduced the proportion of progressing eyes.
Source: Giovanni Montesano , Giovanni Ometto , Anthony King , David F. Garway-Heath , David P. Crabb , Two-year visual field outcomes of the treatment for advanced glaucoma study (TAGS), American Journal of Ophthalmology (2022),
doi: https://doi.org/10.1016/j.ajo.2022.09.011