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

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.

Inclusion:

• Patients are at least 18 years of age.
• Patients must have ocular hypertension or be a glaucoma suspect.
• Patient must not have used any IOP-lowering medication (topical or systemic) within the past 6 months
• Patients must have open angles on gonioscopy.
• All patients will have at least one recorded visual field examination within 6 months of enrollment in the study. Visual fields will be assessed using the Hodapp-Andersen-Parish criteria.

Exclusion:

• Participation in other investigational studies, unless such participation does not involve the administration of any drugs or agents that could impact the results of this study or have an effect on episcleral flow, as determined by the Investigator.
• Prior intraocular surgery other than uncomplicated cataract surgery.
• Allergy or history of adverse reaction to ICG, shellfish, or Iodine.
• Significant liver disease or uremia.
• Secondary glaucoma including exfoliation glaucoma, pigmentary glaucoma, or history of acute angle closure.
• Moderate or severe visual field deficits as per Hodapp-Anderson-Parish criteria.
• Any condition precluding imaging including reliable visual fields, disc photography, or use of study treatments including media opacity or tilted optic disk
• Pregnant or nursing patients.