Evaluation of intraocular pressure and inflammation after Boston K-Pro implantation in Rabbits.

Abstract

Purpose : One of the most common postoperative complications of Boston Keratoprosthesis (B-Kpro) surgery is glaucoma. The pathogenesis is not fully understood, however, elevated intraocular pressure (IOP) and inflammation are known to contribute to retinal and optic nerve degeneration. In this study we investigate inflammation and IOP elevation in a rabbit B-KPro model.

Methods : New Zealand White rabbits (n=6) underwent B-Kpro implantation using autologous corneal graft. During the surgery, the lens was explanted and surgical peripheral iridotomy was performed to prevent pupillary block. Therapeutic partial tarsorrhaphy was applied for one week and daily topical antibiotic prophylaxis was provided for 21 days. IOP measurements were performed at baseline and postoperative days 1, 3, 7, 14 and 21 using a 30G intracameral manometer. IOP elevation (>21mmHg) was treated with timolol maleate 0.5% eye drop (twice daily) until pressure normalization. The eyes were harvested at euthanasia (day 21) for tissue analysis using inflammatory markers CD-45, TNF-α, and GFAP glial marker. Retinal and optic nerve evaluation was performed using β-III-tubulin and p-phenylenediamine (PPD) staining, respectively. ImageJ was used to quantify the data.

Results : All surgeries were successful and uneventful. One week after the surgery, all rabbits exhibited transient IOP elevation ranging from 17±3mmHg to 30±11mmHg (mean±SD, p-value=0.018) which normalized during the following 2 weeks (18±7mmHg, p>0.9). Tissue analysis showed marked upregulation of CD-45 expression in the corneal tissue harboring the device and diffuse TNF-α expression throughout the corneal tissue. In contrast, the retina showed no upregulation of CD-45 or TNF-α expression but a significant increase in GFAP expression in the ganglion cell, inner, and outer nuclear cell layer. Retinal β-III-tubulin expression was significantly down regulated (-16%, p=0.01) and optic nerve axon density was significantly reduced (21%, p=0.03) 21 days after B-Kpro implantation.

Conclusions : This study cast doubts that IOP treatment alone can prevent degeneration in the retina and optic nerve after B-KPro implantation. Suppressing retinal glial cell reactivity using targeted immunotherapy may be an imperative adjunct in the postoperative management of B-KPro patients.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.