Abstract
BackgroundVitreomacular interface conditions can substantially affect vision. In addition, vitreomacular status may influence the clinical course of other diseases such as neovascular age-related macular degeneration (nAMD).
Aims
To investigate the efficacy and safety of intravitreal ocriplasmin or gas for symptomatic vitreomacular adhesion (sVMA).
To assess the effect of vitreomacular interface status (attached or detached vitreous) on antivascular endothelial growth factor (anti-VEGF) drug clearance in nAMD.
To determine the effect of the vitreomacular interface status on the pharmacodynamics and systemic safety of anti-VEGF drugs.
Methods
• A meta-analysis of intravitreal ocriplasmin versus sham or placebo injection for sVMA.
• A pilot study investigating the effect of intravitreal ocriplasmin on hue discrimination measured by serial Farnsworth-Munsell 100 (FM-100) testing.
• A literature synthesis of intravitreal gas for sVMA.
• A clinical trial (VITCLEAR) using serial blood sampling to investigate the systemic pharmacokinetic and pharmacodynamic properties of two different anti-VEGF drugs (ranibizumab and aflibercept) for nAMD. Serum concentrations of the anti-VEGF drug, a panel of cytokines (including VEGF), high sensitivity C-reactive protein (hs4 CRP), and systemic renal function markers were measured at baseline and 11 time points over a time period of one month after intravitreal anti-VEGF injection.
Results
• The meta-analysis of intravitreal ocriplasmin included 932 participants from four randomised controlled trials. Ocriplasmin, when compared to control, was more likely to result in VMA release within 28 days (risk ratio 3.46, 95% confidence interval 2.00 to 6.00). Those receiving ocriplasmin were more likely to have an adverse event than control participants (risk ratio 1.22, 95% confidence interval 1.09 to 1.37).
• Thirteen patients were included in the hue discrimination pilot study. The FM-100 mean total error score worsened from 331.4 to 371.6 at one week (p = 0.29), and reduced further to 397.1 at one month (p = 0.40), before recovering to 349.1 at one year (p = 0.19).
• The literature synthesis of gas for sVMA included 91 eyes and found anatomic success in 48% at one month, and 57% at final review. Safety was acceptable, although there were retinal detachments in two highly myopic eyes.
• The VITCLEAR study included 53 participants. The systemic half-life of aflibercept was decreased when a posterior vitreous detachment was present compared to those with an attached posterior hyaloid, but not significantly so (20.6 days versus 23.3
days; p = 0.66). Compared to baseline, those who received aflibercept had a significant reduction in their serum VEGF concentration at one week and one month (104.5 vs 19.5 vs 39.6 ng/L, respectively; p < 0.01 at both time points compared to baseline), whereas those receiving ranibizumab had no change (139.3 vs 125.9 vs 133.4 ng/L, respectively; p = 0.10 and p = 0.61). Serum concentrations of renal function markers were unchanged from baseline to one month in both anti-VEGF
drug groups.
Conclusion
• For sVMA, there is evidence that ocriplasmin is an effective first line treatment, with an acceptable safety profile.
• Further studies are required to determine the effect of ocriplasmin on hue discrimination.
• Gas appears to be an effective treatment for sVMA, but retinal detachment can occur and larger studies are needed to determine the relative risk versus benefit, particularly in myopic eyes.
• The vitreomacular interface may influence the systemic anti-VEGF drug pharmacokinetics of aflibercept, but larger studies are needed to verify this nonsignificant difference. Intravitreal aflibercept results in a significant reduction of systemic VEGF concentration, whereas ranibizumab does not. Further work is needed to determine whether those with reduced serum VEGF levels have an altered systemic safety profile.
| Date of Award | 1 Jul 2023 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Timothy Jackson (Supervisor) & David G Charteris (Supervisor) |