Evaluation of a steroid delivery system to mitigate the severity of proliferative vitreoretinopathy in a minipig model

Abstract

Purpose: To investigate the efficacy of liposomal prednisolone phosphate to mitigate the severity of proliferative vitreoretinopathy (PVR) in a minipig model of PVR.

Methods: A total of 18 eyes of 9 minipigs underwent PVR induction surgically. Eyes were randomized equally into three groups: intravitreal injection of liposomal prednisolone phosphate (LPP), triamcinolone acetonide (TA), and controls. PVR severity was graded on fundoscopic examination using a modified version of the Silicon Study Classification System. Severe PVR was defined as grade 2-5 on this classification, and the proportion of eyes with retinal detachment from severe PVR, defined as retinal re-detachment, i.e., PVR grade 2-5, was compared between treatment and control groups.

Results: On day 28, five eyes (83.3%) in the control group were observed to have severe PVR. Within the LPP group, one (16.7%) eye developed retinal detachment due to severe PVR. Grade 0 PVR was observed in four (66.7%) eyes, grade 1 in one (16.7%) eye, and grade 5 in one (16.7%) eye. Within the TA group, grade 0 PVR was observed in four eyes (66.7%), grade 1 in two eyes (16.6%), and grade 5 in one (16.7%) eye. The difference in the proportion of eyes with severe PVR was significantly lower in the LPP group compared to controls at day 28 (16.7% vs 83.3%, p=0.02). There was no significant difference in the rate of severe PVR or median PVR grade between the liposomal prednisolone phosphate and triamcinolone acetonide groups.

Conclusion: Liposomal prednisolone phosphate reduces the severity of PVR in a minipig model of PVR.

Keywords: animal model; drug delivery; liposome; proliferative vitreoretinopathy; retinal detachment.

Figure 1

Fundus color photographs and optical coherence tomographic (OCT) scans of an eye with grade 5 PVR (A-C) and grade 1 PVR (D-F). (A) Fundus photograph shows a totally detached retina with folds (white arrow). (B) Infrared en face image of the detached retina. The highlighted green line indicates the scan segment shown in (C), where the folding of the detached retina (white arrow) can be seen. (D) Fundus photograph shows the attached retina with epiretinal/intraretinal pucker (white arrow). (E) Infrared en face image shows the distortion of a retinal vessel (white arrow) crossing the area of the pucker. The highlighted green line indicates the scan segment shown in (F), where distortion of the inner retina (white arrow) can be seen. (G-I) Fundus color photograph, infrared en face and OCT image of an eye with no PVR.

Figure 2

Histology and immunohistochemistry slides of a minipig eye with severe proliferative vitreoretinopathy (PVR) shown at 10x (left) and 20x (right) magnification. (A) H&E staining demonstrates folding of the retina, a characteristic of PVR. Positive staining for the following (white arrows) can be seen associated with the subretinal surface of these retinal folds: (B) Macrophages (RAM11 stain), a major inflammatory cell type involved in the PVR process, (C) Alpha smooth muscle actin, a marker for myofibroblasts derived mainly from de-differentiated RPE cells, and (D) Glial fibrillary acid protein (GFAP), a marker of glial cells. E-H:10x (left) and 20x (right) magnification of the H&E (E), RAM11 (F), alpha smooth muscle actin (G), and GFAP (H) staining of a minipig eye without PVR.