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Biomedical subjects

J P Gilbard

Publications and source records attributed to J P Gilbard.

At least 19 recordsLinked to original sources
PubMed1994

Treatment of keratoconjunctivitis sicca in rabbits with 3-isobutyl-1-methylxanthine.

OBJECTIVE: To examine the effects of topical 3-isobutyl-1-methylxanthine treatment on tear-film osmolarity, conjunctival goblet-cell densities, and corneal epithelial glycogen levels in a rabbit model for keratoconjunctivitis sicca. METHODS: Keratoconjunctivitis sicca was surgically induced in the right eyes of 16 rabbits. In a masked protocol, eight of these operated-on eyes underwent treatment for 12 weeks with a 3.0-mmol solution of 3-isobutyl-1-methylxanthine. The remaining eight operated-on eyes were left untreated and served as controls. RESULTS: The 3-isobutyl-1-methylxanthine treatment resulted in a rapid and significant decrease in tear osmolarity and sodium (P < .5) and potassium levels (P < .05) and a significant increase in conjunctival goblet-cell densities and corneal epithelial glycogen levels compared with untreated and operated-on controls (P < .001). CONCLUSIONS: 3-Isobutyl-1-methylxanthine rapidly and significantly decreased tear-film osmolarity in this rabbit model for keratoconjunctivitis sicca and restored conjunctival goblet-cell densities and corneal glycogen levels, thus reversing the disease process.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Treatment of persistent epithelial defects in neurotrophic keratitis with epidermal growth factor: a preliminary open study.

We report three patients with persistent epithelial defects in the context of neurotrophic keratopathy that healed while on treatment with topically applied, mouse-derived epidermal growth factor (m-EGF). The clinical course of these patients was striking and suggests that EGF may have a potential role in the treatment of persistent epithelial defects in subjects suffering from neurotrophic keratitis.

Administration, Topical↗
PubMed1992

An electrolyte-based solution that increases corneal glycogen and conjunctival goblet-cell density in a rabbit model for keratoconjunctivitis sicca.

Thirty-two rabbits with monocular surgically induced keratoconjunctivitis sicca (KCS) underwent masked treatment for 12 weeks with 1 of 4 artificial tear solutions. Disease in each group of treated rabbits was compared with disease in untreated KCS controls. One of the solutions tested was a unique electrolyte-based formulation shown previously to preserve normal goblet-cell density after extended exposure in normal rabbits. Only the electrolyte-based solution decreased elevated tear osmolarity and sodium after 9 weeks of treatment (P less than 0.05). At 20 weeks, mean corneal glycogen and conjunctival goblet-cell density in eyes treated with the electrolyte-based solution increased significantly relative to untreated KCS controls (P less than 0.01). With the other three solutions, mean glycogen levels and goblet-cell densities were either decreased relative to untreated KCS controls (P less than 0.05) or were unchanged. The electrolyte-based solution is the first treatment to increase corneal glycogen and conjunctival goblet cells in a rabbit model of KCS.

Animals↗
PubMed1992

Decreased tear osmolarity and absence of the inferior marginal tear strip after sleep.

To better understand some of the clinical syndromes that patients experience on eyelid opening in the morning, we examined four patients clinically and measured tear osmolarity immediately after sleep and later in the day. The inferior marginal tear strip was absent, and tear osmolarity was at its nadir on eyelid opening after sleep. We propose a mechanism whereby decreased osmolarity, together with a probable decrease in tear volume, may increase lid-corneal and soft contact lens-corneal adhesion during sleep, and help explain both the development of recurrent corneal erosions on awakening and the tendency of soft contact lenses to adhere to the cornea overnight.

Adult↗
PubMed1991

Stimulation of tear secretion and treatment of dry-eye disease with 3-isobutyl-1-methylxanthine.

We examined the effect of topically applied 3-isobutyl-1-methylxanthine (IBMX), a known secretagogue, on tear secretion and dry-eye disease in a clinical study. We found that IBMX produced a dose-dependent decrease in tear film osmolarity that was significant at 3.0 mmol/L (P less than .0005) in patients with dry-eye disease. This effect was not blocked by prior administration of proparacaine hydrochloride (P less than .05). Throughout a 4-week, open-label, vehicle-controlled study, IBMX decreased tear film osmolarity significantly, whereas vehicle alone did not. After 4 weeks, mean (+/- SEM) osmolarity in IBMX-treated eyes decreased from 325 +/- 3.2 mOsm/L to 312 +/- 1.8 mOsm/L but remained unchanged in vehicle-treated eyes (323 +/- 4.4 mOsm/L vs 320 +/- 4.2 mOsm/L). In our study, IBMX was significantly more effective than vehicle alone in decreasing rose bengal staining (P less than .02). Hence, topical IBMX stimulated tear secretion and decreased ocular surface disease in patients with dry-eye disease.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Tear film and ocular surface changes in a rabbit model of neurotrophic keratitis.

The authors studied the tear film and ocular surface in a rabbit model of neurotrophic keratitis to determine the extent to which the surface disease of neurotrophic keratitis resembled keratoconjunctivitis sicca. After denervation, tear film osmolarity increased and remained significantly elevated for 14 weeks. The ocular surface developed decreased conjunctival goblet cell density, decreased corneal epithelial glycogen, and morphologic changes similar to those seen in keratoconjunctivitis sicca. Although the conjunctival changes were consistent with the increases in tear film osmolarity and the surface disease of keratoconjunctivitis sicca, the corneal changes observed with denervation, including slit-lamp findings, morphologic changes, and decreases in glycogen, were too severe and rapid in onset to be accounted for by osmolarity alone. Neurotrophic "keratitis" is an ocular surface disease composed in part of the surface disease of keratoconjunctivitis sicca. However, the data also support an additional mechanism for corneal disease that could be due to the trophic influence of the trigeminal nerve.

Animals↗
PubMed1990

Eledoisin and lacrimal secretion in the rabbit.

Eledoisin has been tried as a possible treatment for dry eye based on the hypothesis that it pharmacologically stimulates tear secretion when topically applied to the eye. To determine if topically applied eledoisin pharmacologically stimulates orbital lacrimal secretion, the orbital lacrimal gland excretory duct of normal rabbits was cannulated, and eledoisin was applied topically with and without prior administration of proparacaine. To determine if topically applied eledoisin stimulated accessory lacrimal gland secretion, isotonic buffer with and without eledoisin was tested in a rabbit model with only accessory lacrimal tissue remaining after the administration of proparacaine. Topically applied eledoisin did not pharmacologically stimulate lacrimal secretion but rather increased lacrimal gland secretion only in non-anesthetized eyes through a sensory reflex mechanism that is blocked by proparacaine.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Stimulation of tear secretion by topical agents that increase cyclic nucleotide levels.

The authors examined the effect of topical application of agents known to increase cyclic nucleotide levels on tear secretion by accessory lacrimal gland tissue in their rabbit model for keratoconjunctivitis sicca (KCS). Tear secretion was studied by changes in tear film osmolarity and tear volume caused by application of the agents relative to application of isotonic buffer solution alone. A decrease in tear film osmolarity or increase in tear volume was interpreted as an increase in tear secretion. Irritative stimulation was distinguished from pharmacologic stimulation by the prior use of topical proparacaine. The following agents significantly decreased tear film osmolarity and increased tear volume: vasoactive intestinal peptide (2 X 10(-8) to 2 X 10(-6) M); three pro-opiomelanocortin fragments alpha-, beta-, and gamma-melanocyte stimulating hormone at 10(-4), 10(-3), and 10(-3) M, respectively; the permeable cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) analogs 8-Br cAMP (0.3-3.0 X 10(-3) M) and 8-Br cGMP (1.0-10.0 X 10(-3) M); and the cyclic nucleotide phosphodiesterase inhibitor 1-isobutyl-3-methyl xanthine (0.3-3.0 X 10(-3) M). Forskolin (2 X 10(-4) M), which activates the catalytic subunits of adenyl cyclase, increased tear volume significantly. Secretin, adrenocorticotropic hormone, and pilocarpine were ineffective. The authors conclude that agents that increase either cAMP or cGMP levels pharmacologically stimulated tear secretion when applied topically to rabbit eyes with surgically induced KCS.

Administration, Topical↗
PubMed1989

Ophthalmic solutions, the ocular surface, and a unique therapeutic artificial tear formulation.

In rabbit studies, we found that extended exposure of the ocular surface to existing ophthalmic solutions resulted in gross surface abnormalities and decreases in conjunctival goblet cell density. We developed an electrolyte solution (solution 15) that preserves normal gross appearance, goblet cell density, corneal epithelial glycogen levels, and ocular surface morphologic characteristics after extended exposure to the rabbit ocular surface. We created an artificial tear formulation by adding a demulcent and a buffering system to solution 15 and reducing its osmolarity to 162 mOsm/l. We then compared our artificial tear formulation to Hypotears in a double-masked, crossover study involving 11 patients with dry-eye disorders. Our artificial tear formulation was more effective than Hypotears in decreasing tear film osmolarity and rose bengal staining, and was preferred subjectively by an eight-to-one margin.

Adult↗
PubMed1989

Tear film and ocular surface changes after closure of the meibomian gland orifices in the rabbit.

To determine whether meibomian gland dysfunction can increase tear film osmolarity and produce ocular surface changes analogous to those seen with lacrimal gland disease (keratoconjunctivitis sicca [KCS]), the authors closed the meibomian gland orifices in the right eyes of 11 rabbits by light cautery and studied the changes for 20 weeks. Tear film osmolarity was increased throughout the observation period. Conjunctival goblet cell density and corneal epithelial glycogen levels declined progressively. Closure of the meibomian gland orifices thus increased tear film osmolarity in the presence of normal lacrimal gland function and caused ocular surface abnormalities similar to KCS.

Animals↗
PubMed1989

Open-label crossover study of vitamin A ointment as a treatment for keratoconjunctivitis sicca.

The authors evaluated the efficacy of all-trans retinoic acid (vitamin A) ointment as a treatment for keratoconjunctivitis sicca (KCS) in a group of 11 patients selected on the basis of clinical history, slit-lamp examination results, rose Bengal staining, and tear film osmolarity. In this open-label crossover study, vitamin A ointment was no more effective than placebo in increasing tear secretion, as indicated by Schirmer test with proparacaine or tear film osmolarity, or in decreasing ocular surface disease, as indicated by rose Bengal staining. Seven patients stated some preference for the placebo ointment, two patients for the vitamin A ointment, and two patients had no preference.

Adult↗
PubMed1989

Natural history of disease in a rabbit model for keratoconjunctivitis sicca.

We have continued our study of the tear film and ocular surface in our full KCS (keratoconjunctivitis sicca) rabbit model up to 52 weeks post-operatively. Tear film osmolarity remains elevated, conjunctival goblet cell density remains decreased, and the conjunctival epithelium remains abnormal. Corneal epithelial glycogen levels decreased progressively, and at 44 weeks post-operatively rabbits developed abnormal rose Bengal staining of the affected cornea that was shown to be associated with morphologic abnormalities at 52 weeks. Rabbits began rubbing the affected eye after the development of corneal staining. Our full KCS rabbit model demonstrates the features of the human disease.

Animals↗