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Preclinical Toxicology/Safety Considerations in the Development of Ophthalmic Drugs and Devices
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
Robert B. Hackett, Michael E. Stern
Evaluation of the strength and ability of the corneal stroma to heal and withstand trauma is extremely important in evaluating the effects of topical and intraocular formulations. This impacts on postoperative healing of corneal transplants, cataracts, and refractive surgeries such as radial keratotomy and epikeratophakia. In this technique a 9 mm corneal incision is placed in the central cornea and closed with four interrupted 10.0 nylon sutures. The cornea is allowed to heal for a predetermined period of time (usually 6 to 9 days). At this time the rabbit is humanely euthanized and a needle is placed in the anterior chamber which is attached to an infusion pump. Another needle is placed in the anterior chamber which is attached to a pressure transducer and physiograph. As saline is pumped into the eye, the pressure increases and is recorded by the transducer and physiograph. The pressure increases until the incision fails, which is marked by a sudden decrease in monitored pressure. The peak of the pressure curve is called the bursting pressure.9 This pressure can be compared to others in corneas treated with test formulations, either topically or intraocularly. Steroids, for example, are known to decrease the bursting pressure of a corneal wound at various time points.
Corneal onlays and inlays
Published in Pablo Artal, Handbook of Visual Optics, 2017
The efforts toward development of a synthetic corneal onlay have been more recent [11–13]. A corneal onlay is intended to be placed at the very anterior aspect of the corneal stroma, often anterior to Bowman’s membrane after removal of the epithelium, and the epithelium is either replaced or regrows over the surface of the onlay. Epikeratophakia is a technique where donor corneal stromal tissue is formed into a lenticule and added to the anterior corneal stroma to correct high refractive errors, such as those due to aphakia. Long-term viability of these lenticules, however, was often hampered by remodeling and epithelial tissue abnormalities [14–16]. Bioderived tissues were also developed and studied and found to have similar issues to donor corneal stroma [17,18]. In 1989, Colin described the development of synthetic keratophakia onlays that could be placed on the corneal surface without sutures [19]. Later development of the onlay was for the replacement of extended wear contact lenses, since this contact lens wear modality had been shown to cause corneal ulcers and other physiological issues. Synthetic onlays provide potential solutions for conditions such as corneal scarring, keratoconus, or high refractive error, in that they are essentially implantable contact lenses [11]. Evans et al. in 2002 described the development of a polymer that exhibited the required characteristics for an implantable contact lens [20]. Although significant work has been done in this area, to date corneal onlays have only been implanted in animal models and nonsighted human eyes with limited success.
Machines and Instrumentation
Published in Pradeep Venkatesh, Handbook of Vitreoretinal Surgery, 2023
Photic retinopathy results from the toxic effects of photochemical, photothermal, and mechanical interaction between light and retinal tissue. Tso first reported the possibility of retinal phototoxicity from artificial light under experimental conditions in rhesus monkey eyes in 1973. Subsequently, several other reports appeared following cataract extraction, epikeratophakia, triple procedure, vitreous surgery, Molteno implant, and pterygium surgery. The actual incidence from operating microscope–induced macular phototoxicity remains poorly defined with estimates ranging from 3% to 28%. The main sources of retinal phototoxicity during vitreoretinal surgery are indirect ophthalmoscope, operating microscope, and endoilluminator probes. Recognized time thresholds beyond which photic retinopathy could occur are 4.0 to 7.5 minutes for a 30W operating microscope and 15 minutes for the indirect ophthalmoscope. For endoilluminators, it depends on the light source, distance from the retina, diameter, and divergence of the beam. The shape and size depend on the light source. Operating light–induced lesions are sharply defined and are rarely more than 1–2 disc areas, while endoilluminator lesions are larger and have less distinct margins. The location of the lesion in operation microscope–induced photic maculopathy is typically superior or inferior to the fovea. This is determined by the effect of the bridle suture and because the coaxial light is normally 1.5–6 degrees off normal. Because phototoxicity has a cumulative effect, reducing surgical time under the microscope and endoilluminator would reduce the risk of this ‘invisible’ and delayed complication.
Presence of Panel-reactive Antibodies after Penetrating Keratoplasty
Published in Ocular Immunology and Inflammation, 2023
Albert Y. Cheung, Joseph H. Jeffrey, Khaliq H. Kurji, Matthew R. Denny, Amit Govil, Edward J. Holland
Statistical analysis was performed to determine whether there was a significant difference between patients with a single PK graft with good function compared to those with prior sensitization to a previous corneal allograft (multiple PKs). We defined “good function” as a keratoplasty without history of acute rejection with no clinical corneal edema. In those patients with multiple PKs, history of rejection episode or other graft failure etiology are detailed in Table 1. Means between groups were compared with Student’s t-test assuming unequal variances. Relative risk analysis for etiology was performed by comparing elevation of PRA for multiple PK etiology categories compared to the single PK group as control (non-exposuregroup). Etiology categories were divided as follows: corneal dystrophy/degeneration (including Fuch’s, Avellino, lattice, and keratoconus), infectious (namely HSV), corneal scarring (including trauma, chemical injuries, aniridia, and SJS), and iatrogenic corneal malfunction (including failed epikeratophakia and pseudophakic bullous keratopathy). A p-value less than 0.05 was considered significant. Statistical analysis was performed with Microsoft Excel (Microsoft, California, USA).
Assessment of patient-reported outcome measures used in corneal transplantation: a systematic review
Published in Clinical and Experimental Optometry, 2022
Mallika Prem Senthil, Ranjay Chakraborty, Jeremiah Lim
The search was undertaken on 2 March 2021and was not limited to any preceding dates. The following search terms were used: ‘*QoL*’, ‘quality of life’, ‘questionnaires’, ‘self-report’, ‘health status indicators’, ‘patient-reported outcome measures’, ‘corneal transplantation’, ‘epikeratophakia’, ‘keratoplasty’, ‘penetrating’, ‘Descemet stripping’ ‘endothelial keratoplasty’, ‘cornea graft’ and ‘cornea transplant’ (Appendix 1). The search was limited to original research published in humans. Forty eight articles were excluded that constituted review articles (n = 6), as well as articles on other subject area (n = 34) and articles on cost-effectiveness/cost utility without PROM data/results (n = 8) (Figure 1). The search strategy and the data abstraction were undertaken by the authors, MP, RC and JL and any discrepancy was resolved by discussion and systematic elimination. The database search was conducted online using Covidence. One article was in French and was translated and included.
Immune Response and Mechanisms of IFN-γ in Administration for Keratomycosis
Published in Ocular Immunology and Inflammation, 2019
Xuedong Zheng, Tianlu Xie, Yan Lin, Juan Yang, Libin Huang, Jingjin Zhang, Xiaoli Han, Jianzhang Hu
A FK model was produced referring to our previous report8 using epikeratophakia with the aid of corneal epithelium erosion with a minor modification. The mice were anesthetized with intraperitoneal injections of ketamine (50 mg/kg) and xylazine (10 mg/kg); proparacaine hydrochloride (0.5%) was used topically for corneal anesthesia. The central corneal epithelium was removed at a diameter of 2 mm before a full-thickness rat corneal button was placed on the mouse cornea, and 5 μL of inoculum were injected into the space between the two corneas. Then, tarsorrhaphy was performed with two interrupted 7–0 Nylon sutures to limit excursion of the rat corneal button, and another 5 μL inoculum were injected into the conjunctival sac. After surgery, 0.3% ofloxacin eye ointment (Tarivid; Santen, Osaka, Japan) was administered to the palpebral edge immediately.