Scott R. Rossi

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.

A Proposed Mechanism for Increased Tear-Film Osmolarity in Contact Lens Wearers

Contact lenses decrease corneal sensitivity and increase tear-film osmolarity. To determine whether the decrease in corneal sensitivity is responsible for the increase in tear-film osmolarity, we studied tear-film osmolarity in normal rabbits and rabbits with surgically induced keratoconjunctivitis sicca before and after the instillation of 0.5% proparacaine. Instillation of proparacaine resulted in a significant increase in tear-film osmolarity. Decreased corneal sensitivity, with a resultant decrease in tear secretory rates, is the most likely cause for increased tear-film osmolarity in wearers of hard contact and extended-wear soft contact lenses.

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.

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.

Natural history of disease in a rabbit model for keratoconjunctivitis sicca

Abstract 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.

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.

Changes in Tear Ion Concentrations in Dry-Eye Disorders

Meibomian gland dysfunction and autoimmune lacrimal gland disease both increase tear film osmolarity, the former by an increase in tear film evaporation, and the later by a decrease in tear secretion.1 In both cases the surface disease that results is known as keratoconjunctivitis sicca (KCS) and is characterized by decreased conjunctival goblet-cell density and corneal glycogen levels, specific epithelial abnormalities, and rose Bengal staining.2–9

Increased tear secretion in pancreatic cholera: a newly recognized symptom in an experiment of nature

Hormone producing non-B islet cell tumors can be considered experiments of nature because the clinical manifestations allow determination of the pathophysiologic or pharmacologic functions of the peptides produced, and suggest physiologic functions as well. The roles of gastrin as a normal regulator of hydrogen secretion by the stomach and of vasoactive intestinal peptide (VIP) as a regulator of sodium and chloride transport by the intestine were strongly suggested by the clinical manifestations of tumors producing these respective peptides [l]. Herein, we describe a patient with a VIP-producing pancreatic adenocarcinoma who had secretory diarrhea and increased tearing. This case suggests a role for VIP in regulation of human lacrimal gland secretion. CASE REPORT A 35-year-old woman with a previous diagnosis in 1982 of pancreatic cholera secondary to a VIP-producing metastatic pancreatic adenocarcinoma [2] was admitted in September 1986 for refractory diarrhea secondary to metastatic VIPoma. The patient complained of continual tearing and epiphora (overflow tears) that were worse at night. She denied associated ocular irritation or eye pain. At this time, her stool volume was 21 liters per 24 hours, her serum VIP level was 2,394 pmol/liter (normal less than 30 pmolfliter), and her serum pancreatic polypeptide level was 28,661 pmol/liter (normal less than 300 pmovliter).

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.

A Unique Therapeutic Artificial Tear Formulation

The tear film has a unique electrolyte balance distinct from aqueous humor and serum.1. We postulated that this electrolyte balance was critical for the maintenance of ocular surface health.