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Editors Selection IGR 22-2

Medical Treatment: Multiple Therapy Slows Rate of Glaucoma Progression

Comment by Tony Realini on:

94971 The glaucoma intensive treatment study: interim results from an ongoing longitudinal randomized clinical trial, Bengtsson B; Lindén C; Heijl A et al. et al., Acta Ophthalmologica, 2022; 100: e455-e462

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Bengtsson and colleagues have reported the interim results of the Glaucoma Intensive Treatment Study (GITS), a prospective randomized trial comparing standard to intensive initial therapy for newly-diagnosed and treatment-naive patients with mild-moderate OAG. In this trial, patients were assigned to initial therapy with either (a) a single topical drug of the investigators' choosing (81% chose a prostaglandin analogue, 19% a beta-blocker); or (b) a fixed-combination of two drug PLUS a third single-agent PLUS 360-degree laser trabeculoplasty (ALT or SLT). No target IOP was established, and treatment adjustments were at the investigators' discretion over three years of follow-up (of a planned five years in total). The primary outcome was rate of progression, compared between groups. In this interim analysis, the rate of progression was -0.5 dB/yr in monotreated patients and -0.1 dB/yr in multi-treated patients (p = 0.03), and both groups had rapid progressors despite therapy adjustments. Treatment was intensified in 42% of mono-treated and 7% of multi-treated patients.

Take-home lesson from this analysis is that applying more treatments lowers IOP more and reduces progression more than applying a single treatment

Median IOP was reduced from 24 mmHg in both groups at baseline to 17 mmHg in monotreated and 14 mmHg in multi-treated eyes and remained stable during follow-up. The top-line take-home lesson from this analysis is that applying more treatments lowers IOP more and reduces progression more than applying a single treatment. The applicability of this finding to clinical practice is less clear, as the treatment protocol in this study does not conform to standards of clinical practice. There was no effort made to match the initial treatment to the patients' individual therapeutic goals. This inevitably resulted in both under-treatment and over-treatment. The former was easily addressed by adding additional therapy as needed. While the latter could also be addressed by withdrawing therapy as needed, some trial participants are certain to have achieved acceptable IOP control with three medications and yet underwent protocol-mandated laser trabeculoplasty in addition, arguably unnecessarily, which cannot be withdrawn. In fairness to the investigators, their research protocol was designed with the specific purpose of showing that more intensive therapy produces better outcomes and was not meant to mimic or define ideal clinical practice. Translating their findings to clinical practice, however, is limited by the mismatch: this is not how we manage - and not how we should manage - our patients in the real world.

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