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Biomedical subjects

Penny A Asbell

Publications and source records attributed to Penny A Asbell.

17 recordsLinked to original sources

Efficacy of topical cobalt chelate CTC-96 against adenovirus in a cell culture model and against adenovirus keratoconjunctivitis in a rabbit model.

BACKGROUND: Adenovirus (Ad), associated with significant morbidity, has no topical treatment. A leading CTC compound (CTC-96), a Co(III) chelate, was found to have potent in vitro and in vivo antiviral efficacy against herpes viruses. In this study CTC-96 is being tested for possible anti-Adenovirus activity. METHODS: The biological anti-adenovirus activity of CTC-96 in concentrations from 5 to 250 ug/ml, was evaluated initially by viral inactivation (viral exposure to CTC-96 followed by dilution and inoculation of cells), virucidal (viral exposure to CTC-96 and inoculation of cells without dilution) and antiviral (effect of CTC-96 on previously adsorbed virus) plaque assays on HeLa (human cervical carcinoma), A549 (human lung carcinoma) and SIRC (rabbit corneal) cells. After verifying the antiviral activity, New Zealand White rabbits were infected with Ad-5 into: 1) the anterior cul-de-sac scarifying the conjunctiva (Group "C+"); 2) the anterior cul-de-sac scarifying the conjunctiva and cornea (Group "CC+"); 3) the stroma (Group "CI+"). Controls were sham-infected ("C-", "CC-", "CI-"). Other rabbits, after "CC", were treated for 21 days with: 1) placebo, 9x/day ("-"); 2) CTC-96, 50 ug/ml, 9x/day ("50/9"); CTC-96, 50 ug/ml, 6x/day ("50/6"); CTC-96, 25 ug/ml, 6x/day ("25/6"). All animals were monitored via examination and plaque assays. RESULTS: In vitro viral inactivation, virucidal and antiviral assays all demonstrated CTC-96 to be effective against Adenvirus type 5 (ad-5). The in vivo model of Ad keratoconjunctivitis most similar to human disease and producing highest viral yield was "CC". All eyes (6/6) developed acute conjunctivitis. "CI" yielded more stromal involvement (1/6) and iritis (5/6), but lower clinical scores (area x severity). Infection via "C" was inconsistent (4/6). Fifty (50) ug/ml was effective against Ad-5 at 6x, 9x dosings while 25 ug/ml (6x) was only marginally effective. CONCLUSION: CTC-96 demonstrated virucidal activity against Ad5 in tissue culture with HeLa, A549 and SIRC cell lines. Animal Model Development: 1) "CC" produced conjunctival infection with occasional keratitis similar to human disease; "CI" yielded primarily stromal involvement; 2) "C" consistently produced neither conjunctivitis nor keratitis.CTC Testing: 1) Conjunctivitis in all eyes; 2) Resolution fastest in "50/9" ("50/9". "50/6" > "25/6" > "-"); 3) Efficacy in "50/6" was not statistically different than "50/9"; 4) Conjunctival severity was lower in treatment groups then controls; 5) Little corneal or intra-ocular changes were noted.

Acute Disease↗

Fluorophotometry as a diagnostic tool for the evaluation of dry eye disease.

BACKGROUND: Dry eye disease is a common debilitating ocular disease. Current diagnostic tests used in dry eye disease are often neither sensitive nor reproducible, making it difficult to accurately diagnose and determine end points for clinical trials, or evaluate the usefulness of different medications in the treatment of dry eye disease. The recently developed fluorophotometer can objectively detect changes in the corneal epithelium by quantitatively measuring its barrier function or permeability. The purpose of the study is to investigate the use of corneal fluorescein penetration measured by the fluorophotometer as a diagnostic tool in the evaluation of dry eye patients. METHODS: Dry eye patients (16 eyes), who presented with a chief complaint of ocular irritation corresponding with dry eye, low Schirmer's one test (<10 mm after 5 minutes) and corneal fluorescein staining score of more than two, were included in the study. Normal subjects (16 eyes), who came for refraction error evaluation, served as controls. Institutional Review Board (IRB) approved consent was obtained before enrolling the subjects in the study and all questions were answered while explaining the risks, benefits and alternatives. All Fluorophotometry of the central corneal epithelium was done utilizing the Fluorotron Master. Each eye had a baseline fluorescein scan performed, after which 50 l of 1% sodium fluorescein dye was instilled. Three minutes later, the fluorescein was washed with 50 ml of normal saline. Fluorescein scans were then started immediately after washing and were recorded at 10, 20, 40, and 60 minutes thereafter. The corneal peak values of fluorescein concentration were recorded within the central cornea in both dry eyes and in controls. RESULTS: Ten minutes after fluorescein installation, patients with dry eye disease averaged a five-fold increase in corneal tissue fluorescein concentration (mean = 375.26 +/- 202.67 ng/ml) compared with that of normal subjects (mean = 128.19 +/- 85.84 ng/ml). Sixty minutes after dye installation, patients with dry eye disease still revealed higher corneal tissue fluorescein concentration (mean = 112.87 +/- 52.83 ng/ml) compared with that of controls (mean = 40.64 +/- 7.96 ng/ml), averaging a three-fold increase. CONCLUSION: Patients with dry eye disease demonstrated an increased corneal permeability and a slower rate of elimination to topically administered fluorescein when measured by the fluorophotometer. This suggests that fluorophotometry may serve as a valuable quantitative and objective tool for the diagnosis of dry eye disease, and in following patients' response to new treatment modalities. Fluorophotometry may serve as an objective non-invasive tool for end-point analysis in clinical trials of new treatments for dry eye disease.

Adult↗

Intrastromal corneal ring implantation (360 degrees ring) for myopia: a 5-year follow-up.

PURPOSE: Stability of correction is a major factor for successful refractive surgery. Intrastromal corneal rings were placed for the correction of low to moderate myopia beginning 10 years ago. The purpose of this study was to evaluate findings in patients 5 years after ring placement and to compare these findings with 1-year results to assess the stability of effect. METHODS: Seventy-two patients (113 eyes) with myopia (range, -0.75 to -4.50 diopters [D]) were treated with the placement of intrastromal corneal rings (360 degrees ), in a multicenter clinical trial between 1993 and 1994 under U.S. Food and Drug Administration phase II and phase III clinical trials. Six insert sizes were evaluated: 0.21, 0.25, 0.30, 0.35, 0.40, and 0.45 mm. The long-term results that were evaluated were uncorrected visual acuity, best spectacle-corrected visual acuity, cycloplegic refraction spherical equivalent at 5 years and proximity of this value to the target refraction determined preoperatively, induced manifest refraction cylinder, and slitlamp findings. RESULTS: Data at the 5-year follow-up showed that uncorrected visual acuity was 20/40 or better in 83% of eyes and 20/20 or better in 64% of eyes, compared to 88% and 43%, respectively, at the first year of follow-up. Only 7% of eyes lost two or more lines of preoperative best spectacle-corrected visual acuity at 5 years, compared to 11% at the first year. No eyes at the 1- or 5-year follow-up had a best spectacle-corrected visual acuity worse than 20/40. Cycloplegic refraction spherical equivalent was within 1.00 D of target refraction in 68% of eyes at 5 years, compared to 71% at the 1-year follow-up. Induced manifest refraction cylinder greater than 1.00 D was reduced to 5% of eyes in the fifth year, compared to 12% of eyes at year 1. CONCLUSIONS: Intrastromal corneal rings are a safe, effective, and stable method of correcting mild to moderate myopia, and most patients continue to be satisfied with the results after 5 years. There was no clinically significant change in refractive effect and the central corneas remained clear at the 5-year follow-up in all eyes studied. Further data are currently being collected for 10-year follow-up periods. It is hypothesized that the use of intrastromal corneal rings as a refractive option for mild to moderate myopia will be supported by these additional longitudinal data.

Corneal Stroma↗

Susceptibility testing of clinical isolates of pseudomonas aeruginosa to levofloxacin, moxifloxacin, and gatifloxacin as a guide to treating pseudomonas ocular infections.

PURPOSE: Pseudomonas aeruginosa ocular infections most frequently originate from an environmental source; successful treatment with various ocular antibiotics is well established. However, emergence of resistant clones to available antibiotics poses a real threat to successful treatment. The purpose of this study was to evaluate the antibiotic susceptibilities of 100 random clinical isolates of P. aeruginosa to levofloxacin, moxifloxacin, and gatifloxacin, potential agents for the treatment of ocular infections caused by this microorganism. METHODS: One hundred consecutive strains of P. aeruginosa were isolated from clinical specimens submitted to the clinical microbiology hospital laboratory. Duplicate isolates were not included. The minimum inhibitory concentrations (MICs) of these isolates were determined by using Etests, performed according to the manufacturer's instructions. American Type Culture Collection (ATCC) strains of Escherichia coli, P. aeruginosa, and Staphylococcus aureus served as reference controls. RESULTS: Although most isolates were susceptible to levofloxacin, moxifloxacin, and gatifloxacin and the MICs were not significantly different, significant numbers were resistant. The standardized controls rendered expected MICs. The susceptibility of the isolates varied with regard to source, and resistant strains showed increased resistance. CONCLUSIONS: Based on the data, the treatment of ocular infections caused by P. aeruginosa with levofloxacin, moxifloxacin, and gatifloxacin still has a high likelihood of success. However, six of the isolates collected were resistant to all three of the fluoroquinolones tested. Based on the data, clinicians must be aware that clinical resistance can occur even with the newer fluoroquinolones.

Anti-Bacterial Agents↗

Increasing importance of dry eye syndrome and the ideal artificial tear: consensus views from a roundtable discussion.

BACKGROUND: Dry eye syndrome is a highly prevalent, yet largely under diagnosed, condition that can substantially affect quality of life. Left untreated, dry eye is associated with chronic eye pain and increased risk of ocular surface disease. Current demographic changes and lifestyle factors indicate that the dry eye syndrome patient population will increase significantly, ensuring that general practitioners and ophthalmic clinicians alike will experience more patients presenting with dry eye symptoms. Greater public and practitioner awareness of emerging research, technologies, and therapies is crucial to ensuring appropriate interventions to meet specific patient needs and result in clinically favorable outcomes. ROUNDTABLE ASSEMBLY: In August 2005, a team of ocular surface experts convened for a 1-day roundtable session to discuss the latest information on diagnosing and treating dry eye syndrome and real-world issues in artificial tear therapy, including preservative use. ROUNDTABLE DISCUSSION: The discussion centered on the mild to moderate dry eye patient and critical features of the ideal artificial tear, which are preservative-free formulation, protection from microbial contamination, cost-effective, non-blurring, and easy to use. Products that match this profile have the advantage of being able to benefit the myriad of patients who comprise the dry eye syndrome population. Ocular surface health should always remain a top priority. Preferred Practice Pattern Dry Eye Syndrome Medical Treatment guidelines should be modified to recommend the use of preservative-free formula artificial tear products for all levels of dry eye conditions in consideration of the medical benefit they offer to dry eye syndrome sufferers. CONCLUSION: The growing prevalence of dry eye syndrome demands increased attention. Further research, enhanced diagnostic tests, increased use of preservative-free artificial tear formulations as first-line therapy, greater patient-practitioner interaction, and patient education are warranted.

Cost-Benefit Analysis↗

Ten-year follow-up of 360 degrees intrastromal corneal rings for myopia.

PURPOSE: To determine the safety, efficacy, and stability of intrastromal corneal rings 10 years after placement for myopia. METHODS: Ten eyes with myopia treated with the placement of 360 degrees complete intrastromal corneal rings with the ends sutured together were evaluated at 10-year follow-up for the following: uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction spherical equivalent (MRSE), induced manifest refractive cylinder, keratometry readings, slit-lamp findings, and ultrasound central pachymetry. Ten-year data were compared to 1-year results to assess visual stability over time. RESULTS: No statistically significant difference was noted between UCVA at 1 year and 10 years. At the 10-year examination, 90% of patients had BSCVA > or = 20/25 and 100% had BSCVA > or = 20/30. There was no statistically significant difference between MRSE at 1 year and 10 years. At the 10-year examination, induced manifest refractive cylinder was >1.00 diopter (D) in 0% of eyes and < or = 0.25 D in 60% of eyes. There was no statistically significant difference between mean central keratometric power at 1-year follow-up compared with 10-year follow-up. No statistically significant difference was noted in central corneal thickness between 1 and 10 years in the eyes studied. CONCLUSIONS: Intrastromal corneal rings are an effective and stable method of correcting mild myopia based on optic parameters.

Adult↗

Effects of topical antiglaucoma medications on the ocular surface.

The side effects of topical antiglaucoma medications and their preservatives range from ocular discomfort to sight-threatening alterations of the ocular surface. Conjunctival hyperemia, decreased tear production and function, and superficial punctate keratitis are among the most common signs seen on routine clinical examination. Squamous cell metaplasia and changes in cell morphology have been demonstrated by impression cytology studies and evaluation of biopsy specimens, and inflammatory effects are documented by the presence of inflammatory markers. The adverse effects of topical antiglaucoma eyedrops interfere with the treatment of glaucoma on two levels: first, the discomfort produced by the eye drops discourages patient compliance; and, second, long-term treatment with eyedrops is associated with a higher failure of filtration surgery. The detailed mechanism of inflammatory response and/or direct toxicity of eye drops has yet to be determined, but it may vary with the different classes of eye drops, different preservatives, and durations of treatments. Upcoming multicenter trials for new antiglaucoma eye drops should specifically evaluate ocular surface effects.

Journal Article↗

Conductive keratoplasty and the coupling phenomenon.

PURPOSE: To determine whether changes in corneal astigmatism with astigmatic conductive keratoplasty (CK) treatment obey Gaussian coupling (i.e., the steepening of the flat axis associated with the flattening of the steep axis) and to measure the coupling ratio and the coupling constant to determine the effect of astigmatic CK treatment on spherical equivalent. METHODS: Retrospective review of 33 eyes in 24 patients who had undergone CK for hyperopia and who were treated intraoperatively for induced astigmatism. Induced astigmatism was determined by comparison of keratometric readings before and after CK. RESULTS: The coupling ratio was calculated according to two equations: clinical coupling ratio (1.61 +/- 0.81 diopters) and coupling ratio of the surgically induced refractive change (1.57 +/- 1.16 diopters). Values of the coupling ratio between 0.72 and 1.88 indicate coupling. CONCLUSIONS: The cornea does not behave according to Gauss's law of elastic domes. The targeted flat axis and steep axis 90 degrees away are affected by CK in opposite but not equal amounts. Therefore, when correcting surgically induced astigmatism with CK, the overall spherical equivalent of the patient will change because the coupling ratio is not equal to 1.

Astigmatism↗

Intraoperative correction of induced astigmatism after spherical correction of hyperopia with conductive keratoplasty.

PURPOSE: To evaluate the treatment of surgically induced astigmatism intraoperatively during conductive keratoplasty (CK) for correcting hyperopia. METHODS: Conductive keratoplasty uses radiofrequency energy applied to the peripheral corneal stroma to shrink the collagen and alter the central cornea to correct hyperopia. Nineteen consecutive patients (27 eyes) who underwent CK for hyperopia and were treated intraoperatively for induced astigmatism were examined. By using automated keratometric readings taken during the procedure, additional spots were applied at the minus cylinder or flat axis at the 7-mm zone until the intraoperative astigmatism was 2 diopters (D) or less. RESULTS: The intraoperative treatment reduced the astigmatism by an average of 2.30 +/- 1.32 D (P=0.00001). The mean induced astigmatism was 3.33 +/- 0.14 D for eyes that received eight spots, 4.12 +/- 1.13 D for eyes that received 16 spots, 4.43 +/- 0.82 D for eyes that received 24 spots, and 4.60 +/- 1.08 D for eyes that received 32 spots. Additional spots reduced astigmatism in most patients to less than 2 D. CONCLUSIONS: Intraoperative treatment of astigmatism through the addition of more spots at the minus cylinder or flat axis reduced the degree of induced astigmatism. Surgically induced astigmatism was observed more frequently in patients who received 32 treatment spots and 6-mm treatment zone application.

Astigmatism↗

The current state of corneal reshaping.

PURPOSE: The application of contact lenses to alter the shape of the cornea and temporarily reduce or eliminate myopia is known as orthokeratology, corneal refractive therapy, or corneal reshaping. It was first introduced in the 1960s, but high oxygen permeable materials and more sophisticated designs allow patients to wear contact lenses only during sleep, while dramatically improving the predictability and rate of myopia reduction. Many studies have shown that most corneal reshaping patients achieve uncorrected visual acuity of 20/25 or better that lasts all day long in one to two weeks of nighttime wear. Treatment is primarily effective through central epithelial thinning and midperipheral epithelial and stromal thickening. Much remains to be learned about corneal reshaping contact lenses and their effects on the cornea. METHODS: The authors reviewed existing knowledge and determined what needs to be learned in order to provide patients with appropriate informed consent prior to corneal reshaping contact lens wear. RESULTS: While corneal reshaping contact lenses are effective at temporarily reducing or eliminating myopia, claims about the progress of myopia being controlled with corneal reshaping contact lenses should not be made until further studies are published in peer-reviewed literature. The incidence and prevalence of microbial keratitis related to corneal reshaping contact lens wear is not known. Any overnight wear of contact lenses increases the risk of infection, but it is not known whether the risks of microbial keratitis are greater for corneal reshaping overnight contact lens wearers than other form of overnight contact lens wear. It is also not known whether the risk of microbial keratitis is greater for children than adults, but we must determine if children are at greater risk than adults because many children are wearing corneal reshaping contact lenses. CONCLUSIONS: Finally, it is recommended that ongoing education be provided to practitioners and staff regarding safety, informed consent, and prevention of potential problems, with special emphasis on the critical need to properly and thoroughly disinfect lenses that will be worn overnight.

Child↗

P63 expression levels in side population and low light scattering ocular surface epithelial cells.

PURPOSE: Because stem cells exhibit high self-renewal capacity, slow cycling, and high proliferative potential, and one of many markers postulated for epithelial stem cells, p63, is challenged by widespread expression within stem cell-free regions, we examined p63 expression in these stem cell-associated cohorts compared with their controls. METHODS: Rabbit limbocorneal cryosections, cytospun cell-sorted (by fluorescence-activated cell sorter) side population (SP) and low side scatter (LSSC) cells, and limbal epithelial cells over feeders were stained for p63 by indirect immunofluorescence. Clones were fixed and stained daily for 7 days. Image analysis measured p63 intensity, plotting it against colony size. RESULTS: All basal limbal cells were positive for p63, yet only 5% to 7% expressed high p63 intensities, 40% intermediate, and the majority low. Side population cells were less than 1% of total cells. The average intensity of SP staining was three times that of controls. Subpopulations displaying stemlike features exhibited highest p63 expression. Replication rates of isolated cells differed. Day 5 colonies contained 256 (16 hours/cycle) to two (96 hours/cycle) cells. Whereas all cells were positive for p63, intensity in slow-cycling cells was three to four times that in rapidly proliferating congeners. Increased cell doublings did not decrease fluorescence. CONCLUSIONS: Results suggest that p63 concentration is maximal in stem cells and decreases with differentiation. High p63 levels seem to correlate with cells of the SP and LSSC phenotypes, indicating high cell stemness. With identification of stem cells, further studies can elucidate their use in supporting ocular surface health.

Animals↗

Age-related cataract.

Cataract, opacification of the lens, is one of the commonest causes of loss of useful vision, with an estimated 16 million people worldwide affected. Several risk factors have been identified in addition to increasing age--genetic composition, exposure to ultraviolet light, and diabetes. However, no method to halt the formation of a cataractous lens has been shown to be effective. Nevertheless, advances in surgical removal of cataracts, including small-incision surgery, use of viscoelastics, and the development of intraocular lenses, have made treatment very effective and visual recovery rapid in most cases. Despite these advances, cataract continues to be a leading public-health issue that will grow in importance as the population increases and life expectancy is extended worldwide.

Aging↗

Videokeratography in conductive keratoplasty.

PURPOSE: We used EyeSys videokeratography to evaluate corneal shape changes induced by conductive keratoplasty, a procedure that utilizes radio frequency energy to alter corneal shape to correct hyperopia. METHODS: Follow-up data were available for 19 eyes (out of 24 eyes of 13 patients). Preoperative spherical hyperopia ranged from +0.75 to +3.25 D with astigmatism <0.75 D. Manifest refractive spherical equivalent refraction (MRSE), uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), topographical parameter predicted corneal acuity (PCA), corneal uniformity index (CU Index), regular astigmatism, total astigmatism, average simulated keratometry (Avg Sim K), effective refractive power, and asphericity were measured preoperatively and at 6 and 12 months postoperatively. RESULTS: Twelve months postoperatively, mean PCA, CU Index, and BSCVA were maintained at preoperative levels. Mean UCVA (LogMAR) improved from 0.53+/-0.21 to 0.10+/-0.19 (P<.05) with a mean MRSE change from +1.62+/-0.76 D to -0.06+/-0.84 D (P<.05) from preoperative to 12 months postoperative. Mean asphericity increased +0.044+/-0.24 D (P>.05), mean Avg Sim K increased 1.88+/-0.72 D (P<.05), mean effective refractive power increased 1.71+/-0.79 D (P<.05), mean cylinder (cycloplegic refraction) increased 0.19+/-0.36 D (P<.05), mean regular astigmatism increased 0.25+/-0.49 D (P>.05), and mean irregular astigmatism decreased 0.01+/-0.13 D (P>.05) from preoperative to 12 months after conductive keratoplasty. CONCLUSIONS: Avg Sim K and effective refractive power changes support the refractive results; 12-month postoperative maintenance of BSCVA, PCA, and CU Index suggest the procedure is safe. Conductive keratoplasty induced a slight regular astigmatism in some eyes, which decreased with time. The increase in mean corneal asphericity indicated possible induction of central and peripheral cornea changes.

Adult↗