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Vyzulta for POAG shows surprising effect on retinal vessel density

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5 min read

A study recently published in the Journal of Glaucoma evaluated the effect of once daily topical latanoprostene bunod 0.024% (Vyzulta, Bausch + Lomb) on intraocular pressure (IOP) and macular vessel density (VD) in newly diagnosed primary and pseudoexfoliative open-angle glaucoma (OAG) patients.

Give me some background.

Latanoprostene bunod (LBD, 0.024% ) is a nitric oxide (NO) donating modified prostaglandin F2ɑ analog (PGA) that was approved by the FDA for IOP reduction in patients with OAG.

Of note: Endogenous NO relaxes trabecular meshwork cells, facilitates trabecular drainage of aqueous humor, and stimulates a signaling cascade that is part of basal retinal vascular tone.

Bring it back to this study.

Previous analyses of optical coherence tomography angiography (OCT-A) imaging studies have demonstrated that microvascular changes can be observed in different sections of the macula in OAG patients.

As such: The research team utilized OCT-A to demonstrate the possible effect of LBD on retinal microvessels in addition to its IOP-lowering effect.

Now talk about the study.

In this single-center prospective study, investigators included a total of 66 patients with newly-diagnosed OAG and 32 healthy participants:

  • Group 1 (OAG): 66 subjects (mean age 49.4±12.8 years, 53% female)
    • Group 1A (primary OAG [POAG]): 34 subjects
    • Group 1B: (pseudoexfoliative glaucoma [PXG]): 32 subjects
  • Group 2 (control): 32 subjects (mean age 49.6±12.0 years, 56% female)

IOP was measured using Goldmann tonometry while OCT-A imaging was performed at baseline and 1 month following Vyzulta administration to assess changes in VD within multiple retinal layers.

Inclusion criteria?

These included:

  • Age ≥25 years
  • An open angle on gonioscopic examination
  • IOP level ≥21 mmHg on IOP measurements with Goldmann tonometry
  • Diagnosis of OAG, including primary or secondary (pseudoexfoliative) glaucoma in at least one eye

Findings?

In Group 1, the mean IOP decrease in the first month of treatment with LBN was 7.7 mmHg, and the change in IOP was -30.8%.

What about OCTA parameters?

In the superficial slab, the VD in the superior and nasal quadrants was lower in the PXG group compared to the POAG group in the first month of treatment (p=0.038, p=0.019, respectively).

In the choriocapillaris slab, the VD in the superior quadrant at baseline (i.e., before treatment) was statistically lower in both groups compared to the VD in the superior quadrant in the first month of treatment (p<0.001 for both).

  • Meaning: LBN demonstrated significant improvements in VD compared to the baseline.

Expert opinion?

“The amount of IOP reduction (mmHg or %) was not correlated with VD at baseline (pretreatment) or during treatment (except in the superior quadrant of the deep capillary plexus VD [DCPVD]),” the study authors noted.

Further, while this study could not fully explain the mechanism of this effect, the authors pointed out two potential explanations:

  • NO may have caused vasodilation in retinal vessels and increased VD independent of the magnitude of IOP reduction
  • The reduction in IOP may have decreased the stress on the retinal vasculature and improved blood circulation

Limitations?

These included:

  • The sample size was relatively small due to the strict inclusion criteria, which may have limited researchers’ ability to detect changes in patient subgroups
  • The study only evaluated the effect of LBN on VD, and it was unclear if this effect was due to latanoprost or NO
  • Though almost all patients had early-stage glaucoma at the time of diagnosis, the effects of LBN should be (and were not) shown in patients with different stages of disease
  • A lack of evaluation of the effect of LBN on peripapillary vascular structures

Take home.

These findings suggest that treatment with Vyzulta reduced IOP by an average of 29.9% and 31.8% in patients with POAG and PXG, respectively, and improved VD in different quadrants in all slabs.

A large population-based prospective randomized trial is required to validate this effect with definitive data using non-NO-containing PGAs.

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