Pharmacodynamics of Dexamethasone Delivery from a Punctum Plug in Cataract Patients

Abstract

 

Purpose

 

To evaluate the pharmacodynamic performance of dexamethasone delivered from a sustained release punctum plug (OTX-DP) when placed in the vertical canaliculus of the eye for the treatment of ocular inflammation and pain in subjects who have undergone cataract extraction with lens implantation.

 

Methods

 

OTX-DP is a punctum plug containing dexamethasone within a biodegradable PEG hydrogel matrix. The hydrogel is conjugated with fluorescein to aid plug visualization through the tissue using blue light from a slit lamp with a yellow filter. OTX-DP is designed to release dexamethasone into the tear fluid in a tapered profile over 30 days, as shown in Figure One in a preclinical beagle model. The clinical study (NCT01666210) evaluated 60 patients (30 per group) who received either OTX-DP or placebo vehicle punctum plug (PVPP) inserted into the canaliculus of the operated eye at the conclusion of cataract surgery. The PVPP is identical to OTX-DP without the drug. Over 30 days patients were monitored for ocular pain and ocular inflammation (anterior chamber cells and aqueous flare). Plug retention was assessed using a slit lamp.

 

Results

 

Pharmacodynamic indicators in patients comparing the performance of OTX-DP to the PVPP over 30 days are presented in Table One. The OTX-DP over the study duration had more patients with an absence of cells compared to PVPP and this difference was significant at Days 14 and 30. At all time points the absence of ocular pain and anterior chamber aqueous flare was significantly lower for OTX-DP compared to PVPP. The amount of aqueous flare and cells in the anterior chamber is indicative of increased protein content and inflammatory cells and is a sign of intraocular inflammation. OTX-DP retention was 100% through 14 days and 97% at Day 30, and it was considered easy to visualize with a slit lamp.

 

Conclusions

 

Topical corticosteroids treat inflammation for various ophthalmic conditions including postoperative inflammation and pain. The dosing regimen requires multiple daily administrations for at least the first 2 weeks followed by tapering to a lesser frequency as the inflammation subsides. A single dose of OTX-DP at the time of surgery can be a convenient administration option to ensure treatment. Clinical results demonstrated pharmacodynamic performance as indicated in the relief of postoperative pain and reductions in key ocular inflammatory markers of cells and flare.

 

 

 

Keywords: 445 cataract • 487 corticosteroids • 466 clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials