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Henrik Barth, Sven W Crafoord, Fredrik K Ghosh; Developing a retinal detachment model for in vivo testing of vitreous substitutes with repeated pars plana vitrectomy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5941.
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© ARVO (1962-2015); The Authors (2016-present)
In the development of vitreous substitutes, there is a considerable step in translation between preclinical safety studies (in vitro as well as in vivo), and clinical studies. To try and bridge this gap, an in vivo model for treatment of retinal detachment (RD) with vitreous substitutes is explored.
25-gauge pars plana vitrectomy with posterior vitreous detachment was performed in the right eye of 24 pigmented rabbits. Different kinds of ophthalmic cannulas were explored to create a retinal rupture. A subretinal injection of a dilute viscoelastic solution was made through the rupture, with the aim to create a RD. The next day, vitrectomy with fluid/air exchange was performed in 16 eyes, with subsequent injection of Balanced Saline Solution (BSS), SF6 gas or Healaflow® in the vitreous space. The unoperated eyes were used as control. Postoperative clinical evaluation was performed at 1 day, 1 week, and 1 month. After enucleation, the eyes were examined macroscopically, and prepared for histological examination with routine microscopy, TUNEL-assay and immunohistochemistry.
Retinal ruptures and RDs varied in size and configuration depending on surgical technique. Subretinal micro-cannulas were found to be the most versatile, allowing for good control of the size of the RD and rupture. On reoperation, mild to moderate fibrinous reaction in the vitreous was seen in some cases. One eye displayed signs of endophthalmitis and was excluded. Persistent RDs and open ruptures at 30 days were seen in eyes without reoperation, but not in cases with uneventful, repeated surgery. Microscopy and immunohistochemistry showed comparable results for SF6 and Healaflow®.
We here show that clinical rhegmatogenous retinal detachment conditions can be well emulated within the described repeat surgery rabbit vitrectomy model. In some cases, the surgery was technically demanding due to edema and inflammation caused by the original surgery. Future work will be directed towards minimizing postoperative inflammation between surgeries and standardizing instrumentation, allowing for better comparison between different vitreous substitutes. The preclinical platform is well suited for evaluation of potential vitreous substitute candidates pending clinical trials allowing for macroscopic and microscopic evaluation.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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