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Biomedical subjects

Ian J Constable

Publications and source records attributed to Ian J Constable.

25 records · Page 2Linked to original sources
PubMed2003

AlphaCor cases: comparative outcomes.

PURPOSE: To describe clinical outcomes after a novel type of corneal surgery, implantation of an artificial cornea, AlphaCor , and to evaluate outcomes in comparison with alternative keratoprostheses and high-risk grafts. METHODS: Case reports and data from a noncontrolled clinical trial and a literature review. RESULTS: The probability of AlphaCor retention to 1 year is 80%. Postoperative best corrected visual acuity ranges from Perception Light to 20/30. The most significant complications are stromal melts and optic depositions, for both of which the main risk factors have been identified. Complications can be managed without loss of the eye. CONCLUSION: Results from the clinical trial period have helped to determine the indications and risk factors for AlphaCor surgery and to refine surgical techniques. Continued monitoring of outcomes as the series increases will allow a more accurate determination of comparative outcomes. The series provides preliminary evidence that AlphaCor may have a lower incidence of complications than traditional keratoprostheses and may prove to be preferable to a donor graft in high-risk cases.

Aged↗
PubMed2002

The use of synthetic polymers for delivery of therapeutic antisense oligodeoxynucleotides.

Developed over the past two decades, the antisense strategy has become a technology of recognised therapeutic potential, and many of the problems raised earlier in its application have been solved to varying extents. However, the adequate delivery of antisense oligodeoxynucleotides to individual cells remains an important and inordinately difficult challenge. Synthetic polymers appeared on this scene in the middle 1980s, and there is a surprisingly large variety used or proposed so far as agents for delivery of oligodeoxynucleotides. After discussing the principles of antisense strategy, certain aspects of the ingestion of macromolecules by cells, and the present situation of delivery procedures, this article analyses in detail the attempts to use synthetic polymers as carrier matrices and or cell membrane permeabilisation agents for delivery of antisense oligodeoxynucleotides. Structural aspects of various polymers, as well as the results, promises and limitations of their use are critically evaluated.

Animals↗
PubMed2002

The Chirila Keratoprosthesis: phase I human clinical trial.

OBJECTIVE: To undertake a preliminary safety and performance evaluation of an artificial cornea, the Chirila Keratoprosthesis, in human patients. DESIGN: A prospective, interventional case series. PARTICIPANTS: Fourteen consecutive patients with blindness of corneal origin not treatable by repeated standard penetrating keratoplasty. METHODS: Keratoprostheses were manufactured and implanted. The patients, all with preoperative visual acuity of light perception to count fingers (CF), were followed clinically in adherence to a protocol. MAIN OUTCOME MEASURES: Safety (keratoprosthesis retention, incidence of serious complications) and performance (visual acuity, comfort, appearance). RESULTS: Ninety-three percent of keratoprostheses were retained to the date of reporting, up to 2.5 years. One keratoprosthesis (7%) was removed in a manner that restored the patient's preoperative condition. All but one patient maintained their preoperative level of visual acuity or improved on it, with most achieving their estimated full potential visual acuity, (range, count fingers - 20/20). CONCLUSIONS: This keratoprosthesis is acceptably safe and has demonstrated an ability to restore vision in cases in which alternative management would have had a poor prognosis. More extensive trials are warranted.

Cornea↗
PubMed2002

A model for a blinding eye disease of the aged.

This work aims to investigate the effect of compromised lysosomal enzyme activity on the accumulation of photoreceptor-derived debris in the retinal pigment epithelial (RPE) cells and to examine if this accelerated debris accumulation can induce retinal abnormalities similar to those observed in aged individuals. A mutated, enzymatically inactive form of cathepsin D (CatD), generated by site-directed mutagenesis was used to produce stable cell lines and transgenic mice. There was a strong increase in enzymatically inactive CatD protein production in the mutated CatD DNA transfected D407 cells (D407MCD). The presence of the inactive CatD has been linked to an impairment in bovine rod outer segment (BROS) digestion and was confirmed by a statistically significant increase of undigested residual BROS in the medium of D407MCD when compared to the control vector-transfected D407 cells (t-test, P < or = 0.016, P < or = 0.003) or untransfected D407 cells (t-test, P < or = 0.008, P < or = 0.003). The impairment was also confirmed in vivo by demonstration of BROS-derived debris accumulation in the RPE cell layer of transgenic mice. These results demonstrated that the mutated and inactive CatD form could lead to impairment of photoreceptor outer segments (POS) proteolysis. It is proposed that this initial impairment of POS proteolysis may result in the accumulation of CatD-opsin-like complexes in the pigment epithelium, which further compromises RPE cell functions and thus causes the changes observed in aging humans.

Base Sequence↗
PubMed2002

Preclinical evaluation of a phosphorothioate oligonucleotide in the retina of rhesus monkey.

Overexpression of vascular endothelial growth factor (VEGF) has been strongly implicated in the development of choroidal neovascularization (CNV) in patients with age-related macular degeneration. In this study, a phosphorothioate oligonucleotide (PS-oligo) targeting both human and rat VEGF(165) genes upstream of the translation initiation code, named DS135 in this study, was evaluated for its uptake dynamics and retinal tolerance after intravitreal (IV) and subretinal (SR) injections in the rhesus monkey. Intravitreal and SR injections of a fluorescent-labeled DS135 (FL-DS135) resulted in both dose- and time-dependent uptake and persistence, and FL-DS135 remained detectable in the retina for at least 3 weeks after injection. Ophthalmic examination showed transient vitreous haze after IV delivery of a high dose but not with a low dose of FL-DS135. Histologic examination showed no evidence of retinal degeneration with respect to IV delivery. After SR delivery, however, dose-related cellular infiltration, transient residual fluid, and slight distortion of the neuroretina were observed. The biologic efficacy of DS135 was further assessed in a laser-induced CNV model, and development of CNV was determined by fluorescein angiography and histologic examination. Incomplete inhibition of CNV formation was observed after IV and SR injection of DS135, but no statistically significant difference was achieved when compared with dose-matched control of PS-oligo. Analysis of fluorescein angiogram and histologic examination showed less than 30% incidence of CNV development in this monkey model. Our study demonstrated that PS-oligos can be successfully introduced into the retina, although with potential limitations, after SR delivery. DS135, a PS-oligo targeting the VEGF gene upstream of the translation initiation code, partially inhibited CNV formation. An improved CNV model is necessary for further confirmation of the full therapeutic potency of DS135 before clinical application.

Animals↗
PubMedDate not supplied

Telemedicine-friendly, portable tonometers: an evaluation for intraocular pressure screening.

PURPOSE: To evaluate the intraocular pressure (IOP) readings from two portable, telemedicine-friendly tonometers for suitability in glaucoma screening. METHODS: 213 eyes of 107 consenting patients attending an eye clinic were tested with an I-care tonometer and a Pulsair-Easy Eye puff-air tonometer. Gold standard IOP was measured with a Goldmann applanation tonometer (GAT). Effect of central corneal thickness, anterior chamber depth and refractive errors on IOP measurements were also analysed. RESULTS: The mean difference of IOP by GAT and both the portable tonometers was +/- 2.2 mmHg. The analysis indicates minimal difference between IOP readings of both the portable tonometers. The mean difference between two consecutive readings by I-care was 0.01 mmHg. Using 21 mmHg as a threshold for suspected glaucoma, both the portable digital tonometers reported a sensitivity of 38% and specificity of >95%. In the subjects studied, central corneal thickness had statistically significant influence on IOP measurements while refractive errors and anterior chamber depth had no significant influence on IOP measurements with any tonometry. CONCLUSION: The IOP readings by both portable tonometers are comparable and were within clinically acceptable range from GAT. These portable tonometers are useful tools for IOP screening.

Adult↗