Longitudinal Growth Differentiation Factor 15 (GDF15) and Long-term Intraocular Pressure Fluctuation in Glaucoma: A Pilot Study.

Jonathan B Lin,Andrea Santeford,Rajendra S Apte,Arsham Sheybani

doi:10.18502/jovr.v16i1.8245

Jonathan B Lin, Andrea Santeford + Show 2 more

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https://doi.org/10.18502/jovr.v16i1.8245

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Abstract

PurposeGrowth Differentiation Factor 15 (GDF15) was previously identified as a molecular marker of retinal ganglion cell stress in rodent models of glaucoma and was elevated in the aqueous humor (AH) of patients with primary open-angle glaucoma as a possible risk factor for glaucoma progression. The purpose of this study was to determine whether changes in the AH GDF15 levels were associated with intraocular pressure (IOP) changes in eyes undergoing glaucoma surgery.Methods Here, we performed a prospective, longitudinal pilot study in nine patients to determine whether changes in AH GDF15 levels from surgery to post-surgery follow-up were associated with IOP fluctuation. An initial AH sample was taken from the peripheral corneal paracentesis during planned glaucoma surgery, and a second sample was taken during an outpatient follow-up visit, approximately six months later.ResultsThere was a statistically significant correlation between GDF15 fold change and IOP standard deviation (r = 0.87, P = 0.003), IOP range (r = 0.87, P = 0.003), and maximum IOP (r = 0.86, P = 0.003). There was no correlation between the GDF15 fold change and baseline IOP (r = 0.50, P = 0.17), final IOP (r = 0.038, P = 0.92), or mean IOP (r = 0.40, P = 0.28).ConclusionOur findings in this pilot study suggest that longitudinal changes in AH GDF15 may be associated with IOP fluctuation during the postoperative period. Further studies are necessary to corroborate these findings in a larger patient population and to explore the possibility that AH GDF15 may be used not only to improve treatment algorithms but also as a surrogate endpoint in clinical trials.

Highlights

Observational pilot study, we analyzed whether changes in aqueous humor (AH) Growth Differentiation Factor 15 (GDF15) levels from baseline to follow-up at approximately six months were associated with intraocular pressure (IOP) fluctuation
Our findings suggest that AH GDF15 fold change is associated with IOP fluctuation
IOP fluctuation that occurs over months to years has been reported as a risk factor for visual field progression in glaucoma in the Advanced Glaucoma Intervention Study (AGIS),[4, 5] the Collaborative Initial Glaucoma Treatment Study (CIGTS),[6] and the Japanese Archive of Multicentral Databases in Glaucoma ( JAMDIG).[7]

Summary

Introduction

Longitudinal GDF15 and IOP Fluctuation in Glaucoma; Lin et al ganglion cells (RGCs) It is currently the second leading cause of blindness worldwide,[1] the molecular pathogenesis of RGC death remains elusive. Interventions are currently centered on lowering intraocular pressure (IOP), a risk factor for disease progression.[2] Most clinical decision-making is based upon measuring IOP and surrogates of glaucomatous neurodegeneration, such as Humphrey visual field, cup-to-disc ratio, and nerve fiber layer thickness. These surrogate metrics are imprecise in their ability to quantify disease severity and, in some cases, are subjective and unreliable. There is a clinical need for molecular markers that measure RGC health and stress prior to cell death to guide optimal medical and surgical management of glaucoma patients

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