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Editors Selection IGR 12-1

Medical Treatment: Do Prostaglandin Analogs prevent Functional Loss in Glaucoma Suspects?

Comment by Jonathan Crowston & Jess Tang on:

112785 Retinal Ganglion Cell Functional Recovery after Intraocular Pressure Lowering Treatment Using Prostaglandin Analogs in Glaucoma Suspects: A Prospective Pilot Study, Tirsi A; Gliagias V; Sheha H et al., Journal of Current Glaucoma Practice, 2023; 17: 178-190

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Experimental and clinical studies using electrophysiological tests have provided compelling evidence for the concept of functional recovery of 'sick' retinal ganglion cells (RGC) following intraocular pressure (IOP) reduction. The pattern electroretinogram (PERG) is one such method which uses a reversing checkerboard stimulus to measure RGC response¹ and has been shown in several retrospective studies to recover in a subset of glaucoma patients after IOP treatment.^2-4

In this study, the authors used a clinic-based PERG device (Diopsys NOVA-PERG) to evaluate the effect of topical IOP lowering (prostaglandin analogue) in treatment-naive glaucoma suspects (n = 6 patients, eight eyes). Using an optimized protocol for glaucoma (PERGLA), they reported that an IOP reduction of around 22% was associated with a significant increase in the PERG phase (MagD) and PERG ratio (MagD/Mag ratio) after three months. The authors concluded that the increase in MagD reflects faster generation of electrical signals which would be consistent with the recovery of dysfunctional RGCs, while the lack of change in PERG amplitude (Mag) was expected since this reflects the total number of RGC and non-viable RGC would not recover.

This study used a commercially available PERG device, demonstrating its accessibility in the real-world clinical setting. With an established normative database and 'traffic light system' to present results, this simplifies interpretation and clinic adaptation. It should however be noted that this is a very small cohort of non-treated glaucoma suspects with marginally elevated IOP elevation at baseline (mean ± SD: 22.43 ± 2.57 mmHg). Presenting results as an average percent change makes it difficult for the reader to determine whether all individuals improved, or whether only a proportion influenced the overall result. One significant issue with PERG recording is inter-visit variability from factors such as fixation errors, electrode positioning, as well as consistency of ambient room lighting.⁵ Thus, even with a normative database, without first establishing a test-retest repeatability within their cohort, it is impossible to distinguish true change after treatment from intrinsic variability. A further weakness is that despite a lengthy introduction and discussion, many studies that have shown far more convincing functional recovery have been omitted. In addition to this, several

references are incorrect in what is being cited and rather than citing original works the authors chose to cite their more recent additions. Such omissions should have been picked up in the review process.

In summary, the present study provides additional evidence for short-term functional improvement in response to IOP lowering. Larger and longer-term studies are however required to determine whether PERG recovery is sustained and predicts the effectiveness of glaucoma treatment.

Larger and longer-term studies are however required to determine whether PERG recovery is sustained and predicts the effectiveness of glaucoma treatment

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