Monitoring New Long-Lasting Intravitreal Formulation for Glaucoma with Vitreous Images Using Optical Coherence Tomography

Abstract

Intravitreal injection is the gold standard therapeutic option for posterior segment pathologies, and long-lasting release is necessary to avoid reinjections. There is no effective intravitreal treatment for glaucoma or other optic neuropathies in daily practice, nor is there a non-invasive method to monitor drug levels in the vitreous. Here we show that a glaucoma treatment combining a hypotensive and neuroprotective intravitreal formulation (IF) of brimonidine–Laponite (BRI/LAP) can be monitored non-invasively using vitreoretinal interface imaging captured with optical coherence tomography (OCT) over 24 weeks of follow-up. Qualitative and quantitative characterisation was achieved by analysing the changes in vitreous (VIT) signal intensity, expressed as a ratio of retinal pigment epithelium (RPE) intensity. Vitreous hyperreflective aggregates mixed in the vitreous and tended to settle on the retinal surface. Relative intensity and aggregate size progressively decreased over 24 weeks in treated rat eyes as the BRI/LAP IF degraded. VIT/RPE relative intensity and total aggregate area correlated with brimonidine levels measured in the eye. The OCT-derived VIT/RPE relative intensity may be a useful and objective marker for non-invasive monitoring of BRI/LAP IF.

Analysis of Parainflammation in Chronic Glaucoma Using Vitreous-OCT Imaging

“…The left eyes from both models also showed a slight increase in cell number (Figure 7). The results of these two in-depth analyses are in agreement with previous results for relative VIT/EPR intensity [49].…”

“…This technique was validated in subsequent studies [ 46 , 78 ]. Rodrigo et al [ 49 ] described greater vitreous signal in rats with glaucoma than in healthy rats. Recently, a study performed in humans using OCT identified ramified macrophage-like cells on the retinal surface, suggesting a hyalocyte origin (but without histological confirmation), with altered morphology in patients with retinopathies and associated with areas of retinal nerve fibre layer (RNFL) thinning in glaucoma patients.…”

“…Vitreous/retinal pigment epithelium (VIT/RPE) relative intensity was quantified as an indirect measure of immune response [ 44 , 48 , 49 ]. Our custom program finds the internal limiting membrane (ILM) and the inner and outer layers of the RPE by greyscale conversion, obtaining the segmentation of vitreous and RPE ( Figure 1 ).…”

“…Vitreous opacities analysed using OCT can provide rapid correlation with vitreous and intraretinal ocular inflammation and do not require any correction factor for vitreous histological correlation [ 47 , 48 ]. Recently, our group described for the first time an increase in vitreous signal intensity using OCT after induction of ocular hypertension in an animal model of chronic glaucoma [ 49 ]. Our group hypothesizes that, thanks to the optical transparency of the vitreous, the activation and/or increase in the number of hyperreflective vitreous opacities detected in OCT images corresponding to immune cells can be identified more easily than intraretinal ones.…”

Influence of Sex on Neuroretinal Degeneration: Six-Month Follow-Up in Rats With Chronic Glaucoma

“…The retina posterior pole, retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) protocols were used. 39 – 41 , 43 , 44 All of them measured a 3-mm-diameter area centered on the optic disc using 61 b-scans, and subsequent follow-up examinations were performed at this same location using eye-tracking software and a follow-up application. The retina posterior pole protocol analyzed the thickness from the inner limiting membrane to the retinal pigment epithelium divided into the 9 Early Treatment Diabetic Retinopathy areas, 45 which included a central 1-mm circle centered on the optic disc (no fovea exists in rats), and inner (inferior, superior, nasal, temporal) and outer (inferior, superior, nasal, temporal) rings measuring 2 and 3 mm in diameter, respectively, as well as total volume; the RNFL protocol analyzed the thickness from the inner limiting membrane to the GCL boundaries divided into 6 sectors (inferotemporal, inferonasal, superotemporal, superonasal, nasal, and temporal); and the GCL protocol analyzed from the RNFL to the inner nuclear layer boundaries within the Early Treatment Diabetic Retinopathy areas.…”