Safety and efficacy of cyclosporine in the treatment of chronic dry eye.

Dry-eye syndrome (DES) is a multifactorial disease affecting millions of individuals worldwide. Various factors, including age, hormonal status, genetics, sex, immune status, innervation status, nutrition, pathogens, and environmental stress, can alter the cellular and molecular structure or function of components of the ocular surface system. The resulting imbalance increases susceptibility to desiccation and epithelial damage, leading to a vicious circle in which inflammation amplifies and sustains further damage by chronic deregulation of the system. Lubricating agents and steroids have been used as treatment options. However, as the causes of the disease become better elucidated, the more chemically complex cyclosporine A has become an increasingly useful treatment option and in the United States is currently the only Food and Drug Administration (FDA)-approved prescription drug for the treatment of dry eye. The safety and efficacy of cyclosporine have been shown in numerous studies.

Voclosporin as a treatment for noninfectious uveitis.

Voclosporin is a relatively new calcineurin inhibitor that has been used successfully in humans for the treatment of plaque psoriasis. Available data indicate a good safety profile for this treatment and a significant increase in quality of life for psoriasis patients. More recently, voclosporin has been used to treat ophthalmic conditions such as uveitis. The limited data available indicate at least comparable results relative to current therapy with a better safety profile. Here, we analyze data from human and animal studies and the mode of action of voclosporin. Available safety profile data are also discussed.

Treatment of corneal defects with delayed re-epithelization with a medical device/drug delivery system for epidermal growth factor.

BACKGROUND: Human recombinant epidermal growth factor has been shown to be effective in corneal healing when applied topically. The purpose of this preliminary study was to observe whether re-epithelization occurred in patients with non-healing corneal defects treated with a bandage contact lenses impregnated with epidermal growth factor. DESIGN: Prospective non-comparative interventional case series study. Epidermal growth factor-impregnated bandage contact lenses (created through passive transfer of epidermal growth factor into hydrogel contact lenses of high water content) were used to passively release epidermal growth factor to the corneal surface of the damaged eye. PARTICIPANTS: Nine clinical patients who presented for tertiary care at the University of British Columbia Eye Care Centre at Vancouver General Hospital. METHODS: All patients had clinically significant delayed corneal re-epithelization that had not healed despite standard treatments including conventional bandage contact lenses and topical medications. Causes of delayed re-epithelization varied from corneal injuries (e.g. alkali burns, recurrent corneal erosions) to recent corneal surgery (photorefractive keratectomy, phototherapeutic keratectomy, penetrating keratoplasty). MAIN OUTCOME MEASURES: Closure of wounds. RESULTS: Re-epithelialization was seen in the corneas of seven of the nine patients within 8 days after insertion of the epidermal growth factor-treated bandage contact lens into the damaged eye. The drug delivery system appeared to be most effective in non-inflamed corneas. CONCLUSIONS: Preliminary results indicate that bandage contact lenses impregnated with epidermal growth factor may be helpful in promoting re-epithelization in corneas with delayed healing. Efficacy appears to be reduced for vascularized and significantly inflamed corneas.

Gatifloxacin ophthalmic solution for treatment of bacterial conjunctivitis: safety, efficacy and patient perspective.

Gatifloxacin is a fourth generation fluroquinolone antibiotic that has been prescribed for systemic use. However, the drug which was developed by Kyorin (Japan) was linked to toxic reactions and death and was banned in the United States and Canada for use as an oral dosage form. It continues to be used as a topical application for ophthalmic conditions as the systemic toxicity seen when taking the drug orally has not been observed with ophthalmic use. The available data indicate that ocular use of gatifloxacin is safe, and effective against a broad spectrum of bacteria, including intracellular bacteria and anaerobes.

Tafluprost for the reduction of interocular pressure in open angle glaucoma and ocular hypertension.

Tafluprost is an FP receptor antagonist that has been shown in clinical studies in Europe and Japan to be extremely useful in treating elevated intraocular pressure and glaucoma. The drug is well tolerated and appears to be at least equal in effectiveness and perhaps superior to other protanoids for routine use comparison to be superior to other treatments for the elevated IOP as the side effects and other related symptomology appear to be less, while maintaining a level of pressure control for prolonged periods.

Drug delivery to the posterior segment of the eye through hydrogel contact lenses.

PURPOSE: Despite pharmacological advances, delivery of drugs to the posterior segment of the eye remains problematic. We investigated the ability of hydrogel contact lenses to deliver small-molecule steroids, as well as larger biological molecules to the posterior segment. METHODS: Release characteristics of steroid-instilled lenses were studied in vitro. Drug delivery to the posterior segment of the eye was evaluated in a rabbit model, in which hydrogel contact lenses treated with diluted steroids (prednisolone or beclomethasone) were placed on rabbit corneas for four hours on days 1, 2, 5, 8 and 10. The amount of drug in plasma, posterior segment tissue and vitreous humour was measured with high-performance liquid chromatography-tandem mass spectrometry. In a further preliminary investigation, two rabbits were treated with ranibizumab. RESULTS: The lenses released prednisolone and beclomethasone in saline over a six-hour period at a declining rate. Prednisolone was found in posterior segment tissue from six of six rabbits at concentrations ranging from 26.8 to 166 ng/g and in vitreous humour from two of six rabbits. Beclomethasone was detected in posterior segment tissue from three rabbits but was not found in the vitreous humour. Ranibizumab was detected in posterior segment tissue in a range from 0.19 ng/mL to 0.5183 ng/mL. CONCLUSIONS: Hydrogel contact lenses are a non-invasive, periocular drug delivery device capable of achieving measurable drug levels in posterior segment tissue.

Contact lenses as a drug delivery device for epidermal growth factor in the treatment of ocular wounds.

BACKGROUND: This work was conducted to investigate the uptake and release of epidermal growth factor (EGF) from hydrogel contact lenses and to determine whether the released protein would be therapeutically active in a rabbit corneal epithelial defect model of ocular trauma, prior to use in humans. METHODS: The uptake and release of EGF from hydrogel contact lens materials were determined by high-pressure liquid chromatography. Contact lenses composed of vasurfilcon A or lotrafilcon A (containing silicone) were incubated in a source solution containing 0.4 ppm EGF for seven hours. To determine the kinetics of drug uptake into the contact lens matrix, drug concentration in the source solution was measured at zero, one, 60, 240 and 420 minutes. To determine the kinetics of release, loaded contact lenses were immersed in a recipient solution of phosphate-buffered saline. Therapeutic activity in vivo was investigated by placing prepared lenses on the surface of abraded corneas of New Zealand White rabbits, with abraded corneas of contralateral eyes used as controls. Control eyes were treated with contact lenses placed in saline for injection. Wound closure was assessed hourly. RESULTS: Uptake and release of EGF were demonstrated for vasurfilcon A but not lotrafilcon A contact lens materials. The retention time of EGF released from vasurfilcon A contact lenses was similar to control EGF not exposed to contact lens polymers. The greatest adsorption of EGF into the lens material occurred within approximately 120 minutes, with a flattening of the rate of uptake thereafter. Abraded eyes in rabbits showed a significantly higher overall healing rate for EGF-treated contact lenses compared with control eyes (p < 0.0001). CONCLUSIONS: EGF can be delivered from some but not all hydrogel materials. Lens materials composed of silicone may not be useful for delivering EGF to the eye. EGF-treated contact lenses may be a useful device to facilitate healing of ocular wounds.

Making standard of caring part of the standard of care.

Effective risk management focuses on consistent patient communication to inform patients of the benefits of dental health and the breadth of alternative treatments. When education is effective, it helps patients develop new understandings of health and disease. New understandings make appropriate treatment choices possible, and those choices reduce the chances of legal action and contribute to the health of the patient as well as the health of the practice.

A medical device/drug delivery system for treatment of glaucoma.

BACKGROUND: The aim of this study was to investigate the uptake and release kinetics of two common glaucoma drugs delivered onto hydrogel contact lenses using analytical chemistry and to evaluate this device's ability to control intraocular pressure in a limited number of volunteers. METHODS: Contact lenses were incubated in a source solution containing timolol maleate or brimonidine tartrate to determine uptake kinetics. The lenses were then immersed in fresh saline to determine release kinetics. Analysis was performed by high-pressure liquid chromatography (HPLC). HPLC column retention times were determined for drugs released from the lens individually and under co-elution conditions. To evaluate clinical feasibility and toxicity, three volunteers (patients being treated for glaucoma) were provided with contact lenses that had been passively impregnated with either drug. After a three-week wash-out period, the volunteers were instructed to wear the lenses for 30 minutes per day for two weeks. RESULTS: HPLC analysis showed that maximum uptake and release of both drugs had occurred by approximately 60 minutes, with the slopes tending to flatten after this point. The retention time on the HPLC column was 8.08 minutes for timolol maleate and 2.16 minutes for brimonidine tartrate after incubation for one hour, with no changes after seven hours. Patient data showed that use of the lenses maintained IOP at levels equivalent to those obtained with previous treatment. No ocular toxicity was observed. CONCLUSION: Drugs commonly used for glaucoma treatment can be passively transferred to a hydrogel contact lens and then eluted from the polymer. Data obtained from a limited number of patients suggest that this contact lens/drug delivery system may be a feasible means of controlling IOP.