Dataset Information

PYK-1105: Preclinical Evaluation of a Novel Biodegradable Vitreous Substitute for Retinal Tamponade.

ABSTRACT:

Purpose

Current retinal tamponade strategies are limited by anatomic considerations (retinal break location), durability (short-term vs need for removal), and patient adherence (positioning, travel/altitude restrictions). Here we describe the preclinical safety and toxicology of a novel biodegradable hydrogel tamponade agent (PYK-1105) with the potential to improve both patient experience and outcomes after retina surgery.

Methods

We studied in vitro performance to assess hydrogel gelation time, modulus, viscosity, degradation time, refractive index, and transmittance. In addition to studying in vitro and in vivo (mice and rabbits) biocompatibility, testing was performed to assess cytotoxicity, intraocular irritation, acute systemic toxicity, genotoxicity, and pyrogenicity. Furthermore, clinical safety was assessed using in vivo (rabbits and minipigs) response to vitrectomy with PYK-1105 insertion with the following measures: clinical examination, multimodal imaging, full-field electroretinography, and histopathology.

Results

PYK-1105 met the predefined performance testing criteria for optimal tamponade and demonstrated excellent biocompatibility. Animal studies showed the PYK-1105 formulation to be well tolerated and nontoxic in mice, rabbits, and pigs.

Conclusions

PYK-1105 holds promise as a new biodegradable tamponade agent that has the potential to improve both the patient experience and outcomes after retina surgery. Human pilot studies are warranted to further assess for safety and efficacy.

SUBMITTER: Stryjewski TP

PROVIDER: S-EPMC9976048 | biostudies-literature | 2021 Jan-Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PYK-1105: Preclinical Evaluation of a Novel Biodegradable Vitreous Substitute for Retinal Tamponade.

Stryjewski Tomasz P TP Stefater James A JA Roth Larry L Li Jun J Awh Carl C CC Moshfeghi Darius M DM Kim Leo A LA Eliott Dean D

Journal of vitreoretinal diseases 20200901 1

<h4>Purpose</h4>Current retinal tamponade strategies are limited by anatomic considerations (retinal break location), durability (short-term vs need for removal), and patient adherence (positioning, travel/altitude restrictions). Here we describe the preclinical safety and toxicology of a novel biodegradable hydrogel tamponade agent (PYK-1105) with the potential to improve both patient experience and outcomes after retina surgery.<h4>Methods</h4>We studied in vitro performance to assess hydrogel ...[more]

PMID: 37009585

Similar Datasets

Project description:PurposeRhegmatogenous retinal detachment repair by intraoperative sealing of the tear without a tamponade agent should enable faster restoration of vision and resumption of normal activities. It avoids the need for further surgery in the case of silicone oil endotamponade. This study evaluated the retinal thermofusion (RTF) retinopexy method of subretinal space dehydration before photocoagulation to create an instantaneous intraoperative retina reattachment in a preclinical model.DesignPreclinical study.ParticipantsTwenty Dutch Belt, pigmented rabbits that underwent RTF repair after experimental retinal detachment.MethodsThis ex vivo model quantified adhesion force between the retina and underlying retinal pigment epithelium and choroid after treatment of 1 retinal edge using postmortem porcine or human retina (6 × 12 mm). We compared (1) control, (2) laser photocoagulation alone, (3) dehydration alone, and (4) dehydration followed by photocoagulation (RTF). Optimized parameters for RTF were then applied in the in vivo rabbit model of retinal detachment. Animals were followed up for 14 days.Main outcome measuresFor this ex vivo model, we measured adhesion force and related this to tissue temperature. For the in vivo study, we assessed retinal attachment using funduscopy and histologic analysis.ResultsThe ex vivo model showed that RTF repair produced significantly higher adhesion force than photocoagulation alone independent of dehydration method: warm (60° C) high airflow (50-70 ml/minute) or using laser wavelengths targeting water absorption peaks (1470 or 1940 nm) with coaxial low airflow (10-20 ml/minute). The latter approach produced a smaller footprint of dehydration. Application of RTF (1940-nm laser with coaxial airflow) in an in vivo retinal detachment model in rabbit eyes resulted in immediate retinal adhesion, achieving forces similar to those in the ex vivo experiments. Retinal thermofusion repair resulted in stable reattachment of the retina over the 2-week follow-up period.ConclusionsWe showed that a short preliminary dehydrating laser treatment of a retinal tear margin before traditional laser photocoagulation creates an immediate intraoperative waterproof retinopexy adhesion independent of tamponade and a wound-healing response. This approach potentially will allow rapid postoperative recovery regardless of the tear location and improved vision.

Project description:IntroductionRetinal detachment is a sight-threatening emergency, with more than half of those affected suffering permanent visual impairment. A diagnostic test to identify eyes at risk before vision is threatened would enable exploration of prophylactic treatment. This report presents the use of irregularities in retinal shape, quantified from optical coherence tomography (OCT) images, as a biomarker for retinal detachment.MethodsOCT images were taken from posterior and mid-peripheral retina of 264 individuals [97 after a posterior vitreous detachment (PVD), 99 after vitrectomy for retinal detachment and 68 after laser for a retinal tear]. Diagnoses were taken from history, examination and OCT. Retinal irregularity was quantified in the frequency domain, and the distribution of irregularity across the regions of the eye was explored to identify features exhibiting the greatest difference between retinal detachment and PVD eyes. Two of these features plus axial length were used to train a quadratic discriminant analysis classifier. Classifier performance was assessed by its sensitivity and specificity in identifying retinal detachment eyes and visualised with a receiver operating characteristic (ROC) curve.ResultsValidation set specificity was 84% (44/52 PVD eyes correctly labelled) and sensitivity 35% (23/64 retinal detachment eyes identified, p = 0.02). Area under the ROC curve was 0.75 (95% confidence intervals 0.58-0.85). Retinal detachment eyes were significantly more irregular than PVD eyes in the superior retina (0.70 mm versus 0.49 mm, p < 0.05) and supero-temporal retina (1.12 mm versus 0.80 mm, p < 0.05). Lower sensitivity (16/68, 24%) was seen for eyes with a retinal tear without detachment, that were intermediate in size between retinal detachment and PVD eyes. Axial length on its own was a poor classifier. Neither irregularity nor classification were affected by surgery for retinal detachment or the development of PVD.ConclusionsThe classifier identified 1/3 of retinal detachment eyes in this sample. In future work, these features can be evaluated as a test for retinal detachment prior to PVD.

Dataset Information

PYK-1105: Preclinical Evaluation of a Novel Biodegradable Vitreous Substitute for Retinal Tamponade.

Purpose

Methods

Results

Conclusions

Publications

PYK-1105: Preclinical Evaluation of a Novel Biodegradable Vitreous Substitute for Retinal Tamponade.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets