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Editors Selection IGR 16-4

Medical Treatment: Mono- vs. Multitherapy

Comment by Gustavo de Moraes on:

78343 Initial intraocular pressure reduction by mono- versus multi-therapy in patients with open-angle glaucoma: results from the Glaucoma Intensive Treatment Study, Lindén C; Heijl A; Jóhannesson G et al. et al. et al., Acta Ophthalmologica, 2018; 96: 567-572

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Linden et al.¹ compared the effect intraocular pressure (IOP)-lowering between newly diagnosed glaucoma patients treated with mono- versus multi-therapy regimens in a randomized clinical trial. The mono-therapy group (N = 118 patients) received any one of three classes of glaucoma drops commercially-available in Sweden, while the multi-therapy group (N = 122) received three different classes (one fixed combination plus a third class) followed by laser trabeculoplasty (LTP, either selective or argon laser trabeculoplasty). Of note, all eyes had early-to-moderate visual field loss at baseline (visual field index > 65%) and all levels of untreated IOP at study entrance were allowed. The present analysis is part of a larger study goal of assessing whether immediate, more intense treatment or conventional, stepwise treatment would result in better functional and quality-of-life outcomes in the long run in patients newly diagnosed with glaucoma.

To successfully decrease visual disability due to glaucoma worldwide, treatment options in glaucoma need to become more affordable

The first main finding was that, after one month, both the absolute and percentage IOP reduction were dependent upon the baseline IOP levels ‐ with higher baseline measurements resulting in greater reduction ‐ which is consistent with what has been described in a number of studies investigating different types of IOP-lowering interventions. Nonetheless, this effect was more pronounced in the intense (multi-therapy) eyes: for each mmHg higher baseline IOP, these eyes experienced a 0.84 mmHg IOP reduction compared to 0.56 mmHg in the mono-therapy eyes.

Secondly, despite similar median baseline IOP prior to initiation of treatment (median= 24 mmHg in both groups), the multi-therapy group experienced a median pressure reduction 6 mmHg greater than the mono-therapy group (final median IOP = 12 and 18 mmHg, respectively, P < 0.001).

Finally, and perhaps the most relevant finding, multi-therapy enabled achieving pressures lower than several different target IOPs in a greater proportion of patients than mono-therapy. For instance, while an IOP < 18 mmHg was achieved in 49% of eyes in the mono-therapy group, multi-therapy achieved the same target in 92% of eyes. This finding was also true regardless of the baseline IOP. For instance, while an IOP < 14 mmHg was achieved in 34% of eyes whose baseline IOP was < 21 mmHg in the mono-therapy group, that number was 92% in the multi-therapy group.

Although it appears intuitive that more intense medical therapy leads to lower IOP, this is the first report to provide quantitative estimates in a randomized trial. It would have been valuable had the authors also described how the two groups compared in terms of quality- of-life measurements given that IOP drops can adversely affect these estimates due to topical or systemic effects,² even after short periods of follow-up. This will hopefully be addressed in a follow-up publication by the investigators in this database. Although the benefits of multi-therapy were clear after one month, more compelling information will be available in the long-term analysis. Adherence is one major confounder as patients tend to be less compliant when treated with more complex regimens.³

Of course, the long-term effects on visual function and the cost-benefit analyses will be crucial to help clinicians decide whether the new treatment paradigm ‐ which recommends an immediate, intense multi-therapy regimen ‐ should be considered at least in some patients with newly diagnosed glaucoma. The authors should be congratulated for the design of this clinical trial and the novel information to be added to the literature.

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