Measuring the Effects of Netarsudil, Latanoprost, and Combination Therapy on Episcleral and Retinal Blood Flow in Ocular Hypertension and Glaucoma Suspects

Overview

The goal of this clinical trial is to compare participants treated with latanoprost to those treated with Rocklatan (netarsudil/latanoprost) to determine whether the addition of netarsudil results in greater improvements in episcleral venous blood flow in adults with glaucoma or ocular hypertension. Episcleral venous blood flow will be measured using erythrocyte-mediated angiography (EMA) and laser speckle contrast imaging (LSCI). The main questions this study aims to answer are: * Does Rocklatan produce greater increases in episcleral venous blood flow than latanoprost alone? * Can EMA and LSCI reliably detect changes in episcleral venous blood flow following treatment with these medications? Participants will: * Be randomized to receive either latanoprost or Rocklatan * Undergo imaging of the episcleral veins using EMA and LSCI before, during, and after treatment, and * Complete study visits that include standard ophthalmic examinations and intraocular pressure measurements. Hypothesis: The investigators hypothesize that latanoprost, which primarily increases uveoscleral outflow, will not significantly affect the distal episcleral circulation. In contrast, Rocklatan, through its netarsudil component, is expected to produce measurable increases in episcleral venous flow.

Glaucoma is a leading cause of irreversible blindness worldwide, and lowering intraocular pressure (IOP) remains the primary strategy for slowing disease progression. While many glaucoma medications reduce IOP by increasing aqueous humor outflow or decreasing its production, the effects of these therapies on the distal conventional outflow pathway-particularly the episcleral venous circulation-are not well understood. Previous studies using erythrocyte-mediated angiography (EMA)-a novel imaging technique capable of directly quantifying episcleral venous blood flow in vivo-demonstrated that netarsudil (Rhopressa) significantly increases episcleral venous flow while lowering IOP, supporting episcleral blood flow as a biomarker of distal outflow function. This study will build on those findings by comparing the effects of latanoprost and Rocklatan (netarsudil/latanoprost) on episcleral venous blood flow using both EMA and laser speckle contrast imaging (LSCI), a newer, less invasive imaging modality. Investigators will evaluate whether the addition of netarsudil to latanoprost produces measurable improvements in episcleral venous flow beyond those achieved with latanoprost alone. By improving the understanding of how these medications influence the distal outflow pathway, this study may help explain the superior IOP-lowering efficacy of Rocklatan and support the development of noninvasive imaging methods for assessing treatment response in glaucoma. Building on these findings, this study will compare the effects of latanoprost and Rocklatan (netarsudil/latanoprost) on episcleral venous blood flow using EMA and laser speckle contrast imaging (LSCI), a newer, noninvasive imaging modality. Latanoprost, a first-line prostaglandin analogue, primarily lowers IOP by increasing uveoscleral outflow and is not expected to substantially alter distal episcleral circulation. In contrast, Rocklatan combines the effects of latanoprost with netarsudil, which enhances conventional outflow and reduces episcleral venous pressure, and is therefore hypothesized to produce measurable increases in episcleral venous blood flow. By directly comparing these therapies, the study aims to assess whether Rocklatan enhances distal outflow as compared to latanoprost, correlate changes in episcleral flow with IOP reductions to evaluate the role of episcleral modulation as a driver of Rocklatan's enhanced clinical efficacy, and redefine how researchers and clinicians evaluate IOP-lowering therapies by targeting the actual vascular response of the distal outflow system. Ultimately, this work has the potential to clarify the mechanism underlying Rocklatan's superior efficacy, establish episcleral venous flow as a novel biomarker for pharmacologic response, and support further development of therapies that leverage distal outflow enhancement.