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Biomedical subjects

P A Pearson

Publications and source records attributed to P A Pearson.

18 recordsLinked to original sources
PubMed1995

Intravitreal sustained-release dexamethasone device in the treatment of experimental uveitis.

PURPOSE: Uveitis often runs a chronic course requiring long-term therapy. Topical treatment results in poor intravitreal penetration, and systemic therapy is associated with significant side effects. The authors investigated whether an intravitreal sustained-release dexamethasone device was effective in the treatment of severe panuveitis in a rabbit model. METHODS: Twenty New Zealand white rabbits were immunized twice subcutaneously with 10 mg of Mycobacterium tuberculosis H37Ra antigen. Twelve days later, sustained-release dexamethasone devices were implanted into the vitreous of the right eye of 10 rabbits. Ten control rabbits received a sham device. One day later, rabbits were challenged with an intravitreal injection of 33 micrograms of antigen. Three animals in each group were sacrificed on post-challenge days 7 and 13 for aqueous white blood cell (WBC) count, protein determination, and histologic examination. To simulate chronic inflammation with exacerbations, the eight remaining eyes were rechallenged with intravitreal antigen on day 15 and were observed for 3 1/2 months. Inflammation was graded clinically by two masked observers. Retinal function was evaluated by electroretinography (ERG). Light microscopy was used to evaluate the eyes histopathologically. The amount of residual drug in the devices was measured on day 13 and at the end of the experiment. RESULTS: By all clinical criteria measured--anterior chamber cells, flare, and vitreous opacity--treated eyes had significantly less inflammation than untreated eyes (P < 0.05). Clinical examination correlated well with objective data. Both protein concentration (P < 0.05) and aqueous WBCs (P < 0.02) were approximately 10-fold higher, and ERGs were significantly depressed (P < 0.05) in untreated eyes compared to treated eyes. Histopathologic examination showed marked inflammation and tissue disorganization in the untreated compared to the treated eyes. After antigen rechallenge, inflammation in experimental eyes was still less than in control eyes. Late complications such as corneal neovascularization, cataract, and hypotony were also less in the treated eyes than in the untreated eyes. At the end of the experiment (99 days after device implantation), approximately 30% of drug remained in the devices. CONCLUSIONS: The intravitreal sustained-release dexamethasone device is highly effective in suppressing inflammation and preventing complications after two episodes of experimental uveitis in a rabbit model for at least 3 1/2 months. This device may be useful in the management of patients with severe chronic posterior uveitis who cannot tolerate systemic or periocular therapy.

Animals↗
PubMed1994

Review: implants.

An implantable sustained release device has been developed to treat chronic disorders of the eye. The device, consisting of a central core of drug encased in layers of permeable and impermeable polymers, can be implanted subconjunctivally or intravitreally. This technique was used to develop a ganciclovir device which, when implanted into the vitreous, maintains therapeutic vitreous levels of drug for 8 months. Initial studies in patients with cytomegalovirus (CMV) retinitis indicate that this treatment may offer better control of the disease and fewer side effects than existing therapies. Cyclosporine A devices were prepared for the treatment of uveitis. Early data suggests that these devices maintain therapeutic levels in the vitreous for approximately 3 years. Work on efficacy and toxicity is continuing. Although clinical applications of these devices are likely to be restricted to diseases requiring chronic drug therapy, they can be used to investigate optimal delivery rates. Subconjunctivally implanted devices releasing 5-FU for 12 days maintained filters in cynomolgus monkeys for 3 months. Similar devices maintained low intraocular pressure in 75% of high risk filter patients.

Animals↗
PubMed1993

Clearance and distribution of ciprofloxacin after intravitreal injection.

This study was designed to determine the drug concentration and clearance after intravitreal injection of ciprofloxacin. Ciprofloxacin (100 micrograms/0.1 cc) was injected into the vitreous of normal eyes and into eyes that had undergone lensectomy and vitrectomy. Drug concentration was determined using high-pressure liquid chromatography analysis 0.5, 2, 4, and 12 hours after injection. In normal eyes, the elimination half life was 2.2 hours with a distribution volume of 1.2 ml. In aphakic vitrectomized eyes, the half life was 1 hour and the distribution volume was 1.4 ml. The majority of the drug appears to leave via a transretinal route, but clearance was not inhibited by probenecid. Because of the relatively short half life, intravitreal administration of ciprofloxacin for the treatment of endophthalmitis would provide only short-term therapy and would need to be supplemented by other forms of treatment.

Animals↗
PubMed1992

Intravitreal sustained-release ganciclovir.

Current treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome involves frequent intravenous administration of sodium ganciclovir that often results in unacceptable side effects. We have developed devices that release ganciclovir at rates of 2 micrograms/h and 5 micrograms/h in vitro. When implanted into the vitreous of rabbit eyes, mean intravitreal ganciclovir levels of 9 mg/L and 16 mg/L were maintained for more than 80 and 42 days, respectively. Devices were well tolerated, with no toxic effects attributable to the polymers used in the devices. This investigation indicates that these devices can maintain therapeutic levels of drug for extended periods and are well tolerated in the rabbit eye. They may prove useful in the clinical management of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

Animals↗
PubMed1992

Intravitreal ganciclovir pharmacokinetics in rabbits and man.

Cytomegalovirus (CMV) retinitis occurs in immunocompromised patients and can be treated by repeated intravenous or intravitreal injections of ganciclovir (GCV) or foscarnet. Due to toxicity and complications these modalities are not ideal. The development of alternative administration routes is hindered by a lack of pharmacokinetic data. Devices giving pseudo zero order release of GCV were implanted intravitreally first in rabbits and then in patients with AIDS associated CMV retinitis as part of a Phase I clinical trial. Steady state intravitreal GCV levels were obtained immediately after death and the elimination rate constants were calculated assuming first order pharmacokinetics. Normalizing for retinal surface area, distribution volume and anatomic volume, the retinal elimination rate constants were calculated. These were found to be 0.017 cm-2hr-1 in rabbits and 0.015 cm-2hr-1 in man. This indicates that the rabbit eye is a good model for studying intravitreal pharmacokinetics of ganciclovir and suggests a common elimination mechanism which may be trans-retinal.

Animals↗
PubMed1992

Subconjunctival sustained release 5-fluorouracil.

The authors have developed a sustained release device for 5-fluorouracil (5-FU) made up of a 12 mg pellet of drug coated in a mixture of permeable and impermeable polymers. When implanted subconjunctivally in rabbits, these devices released 5-FU at approximately 1 mg/d for over 10 days. Devices were implanted into four cynomolgus monkey eyes after posterior lip sclerotomy. One eye (treatment) received a device that contained 12 mg 5-FU and the other eye (control) received a placebo device that contained no drug. In control eyes, intraocular pressures returned to normal within 1 wk. In treatment eyes, pressures remained significantly lower throughout the experimental period (3 mo). There was no indication of impaired wound healing, corneal toxicity, inflammation, or damage to the ciliary body in rabbits or monkeys.

Animals↗
PubMed1991

Evaluation of optic nerve sheath fenestration in pseudotumor cerebri using automated perimetry.

Evaluation of the efficacy of optic nerve sheath fenestration in pseudotumor cerebri has been hindered by a lack of quantitative indicators of visual function before and after treatment. Nine patients (14 eyes) were treated who had pseudotumor with optic nerve sheath fenestration, in whom automated perimetry was used as a major parameter in the decision to undertake surgery and in evaluating the results. Visual field results demonstrated significant improvement in this group of patients. Seven of 8 eyes with total loss less than 1500 dB had improvement or no further deterioration. Using results of the last preoperative examination as baseline, it was found that six of the eight had improvement over 150 dB. In one patient, a slight deterioration occurred postoperatively. Those eyes with total loss above 1500 dB demonstrated stabilization of fields postoperatively. Statistical analysis of total loss preoperatively and postoperatively for this group of patients demonstrated significant improvement for five of the six comparisons investigated. Average preoperative total loss and average postoperative total loss were not significantly different. Comparisons of results of the last preoperative examination to those of the first postoperative and most recent follow-up examinations, and evaluation of average total loss postoperatively showed significant improvement had occurred. Results of the first postoperative examination and those of the most recent follow-up examination showed significant improvement from the average preoperative total loss.

Adult↗
PubMed1990

The relationship of mean defect to corrected loss variance in glaucoma and ocular hypertension.

Statistical analysis of visual-field data is permitted by the quantitative techniques used in automated perimetry. The visual-field indices mean defect (MD) and corrected loss variance (CLV) provide an opportunity to analyze and follow visual fields mathematically. We investigated the relationship of MD to CLV in 32 glaucoma suspects and 17 patients with visual-field defects due to chronic open-angle glaucoma. In glaucoma patients with early and moderate disease (up to a MD of 18 dB), the CLV statistically covaried with the MD (R2 = 0.85). Beyond an MD of 18 dB, increases in the MD seemed to cause a decline in the CLV. These results differ from prior reports on the relationship of MD and CLV. Reasons for this and implications for the use of these statistics in the clinical management of the glaucoma patient are discussed. These results may be helpful in the understanding of the pathophysiologic basis of damage in glaucoma.

Chronic Disease↗
PubMed1989

Vitreous loss rates in extracapsular cataract surgery by residents.

Vitreous loss is a serious complication of cataract surgery. It has been suggested that high rates of vitreous loss may be an inevitable consequence when residents are learning extracapsular cataract extraction (ECCE). The authors retrospectively analyzed all (n = 936) cataract operations done by second- and third-year residents in a single Veterans Administration hospital from 1982 through 1988. Between 1982 and 1985, the incidence of vitreous loss was 10.3%. In 1985, a new program of resident surgical education was introduced, and the incidence from 1985 through 1988 declined to 3.2% (P less than 0.001). Statistical analysis confirms that this decrease cannot be attributed to any individual surgeon, class of residents, or year of surgery. The authors believe that an educational program including practice surgery, graded responsibility, and experienced assistance may be responsible in part for dramatically reducing the rate of this serious complication during surgery done by the beginning resident.

Cataract Extraction↗
PubMed1989

Anterior chamber lens implantation after vitreous loss.

Vitreous loss is a serious complication of cataract surgery. Following vitreous loss it is common practice to perform a primary implantation of an anterior chamber lens (AC-IOL). We retrospectively analysed 642 consecutive cases of cataract extraction performed between 1983 and 1986 with special attention to those patients in whom vitreous loss occurred and an AC-IOL was placed. There were 27 such cases, and 24 of these were available for follow-up. Eighteen (75%) had visual acuity of 20/40 or better. All six patients (25%) who had a visual acuity of less than 20/40 in the operated eye had a functional visual acuity of 20/200 or less. Complications that occurred in this group are discussed. We are concerned that the complications associated with vitreous loss and with AC-IOLs may be acting in concert to cause visually disabling results.

Aged↗
PubMed1989

The use of viscoelastic substances in the drainage of postoperative suprachoroidal hemorrhage.

Suprachoroidal hemorrhage is a serious surgical complication occurring in up to 10% of aphakic patients undergoing filtration surgery. Surgical treatment includes drainage of the hemorrhage through sclerotomies and reformation of the anterior chamber with balanced salt solution or air. Two patients are presented whose suprachoroidal hemorrhages were managed with the instillation of 10% sodium hyaluronate. The intraocular administration of a space-occupying fluid produces an even distribution of hydraulic force to facilitate drainage of the hemorrhage and avoids the optical problems associated with the use of intraocular air. While most cases of suprachoroidal hemorrhage can be effectively managed using balanced salt solution or air, we believe that viscoelastic agents may be of special benefit in selected situations.

Aged↗
PubMed1989

Lens subluxation as a complication of cyclocryotherapy.

There are many well known complications of cyclocryotherapy. This case represents what we believe to be the first report of cyclocryotherapy leading to lens subluxation. The patient was a 14-year-old boy with a history of ocular trauma that had resulted in intractable glaucoma. Six locations were treated inferiorly using the freeze-thaw-freeze technique. Postoperatively the patient's zonular attachment was disrupted inferiorly and the lens subluxated superiorly. While remote trauma may have been partly responsible, we suspect that the cyclocryotherapy precipitated the lens subluxation.

Adolescent↗
PubMed1987

Endophthalmitis associated with intravenous drug abuse.

Endophthalmitis is an inflammation of the interior of the eye. We describe an IV drug abuser with endophthalmitis who initially was diagnosed as having an acute conjunctivitis. During the next 12 hours fulminant endophthalmitis developed. The patient failed to respond to treatment, and on the second hospital day underwent subtotal exenteration of the right orbit. The only organism obtained from numerous cultures was Staphylococcus epidermidis. We suspect the causative organism was not isolated.

Adult↗