PEG-PPG-PCL thermogelling polymer as tamponading agent in non-human primate retinal detachment model

Abstract

Purpose : We optimized a tri-component thermogelling polymer (PEG-PPG-PCL, EPC) to provide internal vitreous tamponade through swelling pressure and viscosity. The initial results of its use in retinal detachment repair using non-human primate models are presented.

Methods : In vitro studies: Dynamic gel properties were examined wtih oscillation frequency/amplitude sweep experiments. Viscosity temperature ramp and surface tension of thermogelling solutions were measured.
In vivo studies: All animal experiments were approved by Institutional Animal Care and Use Committee, SingHealth, Singapore, in accordance with ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Five macaques underwent three-port, 23G vitrectomy using standard vitreo retinal surgical set up and wide-angle visualization system. Posterior vitreous detachment was induced with forceps and suction, aided by triamcinolone acetonide staining. Retinal detachment was created in midperiphery by injecting BSS subretinally with 41 gauge needle. The site of injection was enlarged with vitreous cutter to mimic a retinal break. Retina was flattened by fluid air exchange and laser was done to the retinal break. Air was replaced with 7% EPC hydrogel and sclerotomies were sutured. The monkeys were followed up by slit-lamp, SD-OCT and ERG for up to 10 months.

Results : In vitro studies show that the thermogel (EPC-7%) provides sufficient viscosity and surface tension. At 37 degrees celsius, an amplitude sweep of 0.1-100 % strain revealed linear viscoelasticity; the surface tension was 220 mN.m^-1; and the viscosity in gel state was 107 Pa.s.
Of the 5 eyes that underwent surgery, 3 had mild inflammation in first 2 weeks. At 1 month all the eyes were quiet; lenses were clear; retina was attached and the vitreous cavity was optically clear. The intra-ocular pressures remained within normal range (12 - 18 mm/Hg). In the monkey that was followed up for 10 months, assessment of retina by OCT confirmed normal retinal architecture at the macula; pattern-ERG showed normal P50 and N95 amplitudes; and the full-field ERG amplitudes and latencies were normal except for a mild reduction in photopic b-wave amplitude.

Conclusions : Our findings demonstrate that in principle, EPC-7% hydrogel has biophysical requirements of an effective internal tamponading agent through swelling pressure and viscosity. The 10 month follow up demonstrates its safety.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.