Mathea R. Allansmith

Giant Papillary Conjunctivitis in Contact Lens Wearers

A syndrome that occurred in both hard and soft contact lens wearers was characterized by increased mucus, itching, decreased lens tolerance, and giant papillae in the upper tarsal conjunctiva. It developed in as few as three weeks with soft lens wearers but also occurred after months or even years of successful wear. The histology was characterized by basophils, eosinophils, and mast cells in the epithelium, and these cells as well as increased numbers of lymphocytes, plasma cells, and polymorphonuclear leukocytes in the stroma. The syndrome may be immunologic in origin with deposits on the lenses as the antigen, and the syndrome may be a major cause of difficulty in wearing contact lenses once they have been successfully fit.

The development of immunoglobulinlevels in man

Summary The development of IgG, IgA, and IgM levels from birth, through the newborn period, infancy, childhood, and into adulthood has been studied with the use of 1,241 sera from 939 subjects. Rapid synthesis of IgM starts in the first week of postnatal life. This system expands to the adult levels by the age of about 1 year for boys and 2 years for girls. Boys and girls have similar IgM values until age 7, after which girls have higher values. IgA synthesis begins by 2 to 3 weeks of age, increases slowly, and attains adult levels by about 12 years. Rapid IgG synthesis probably begins by the first 4 to 6 weeks of life and adult levels are reached at about age 8 years.

Conjunctival Deposition of Eosinophil Granule Major Basic Protein in Vernal Keratoconjunctivitis and Contact Lens-Associated Giant Papillary Conjunctivitis

To investigate the role of the eosinophil in vernal keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis, we assessed the presence of eosinophil granule major basic protein in conjunctival tissues by immunofluorescence. Biopsy specimens of conjunctiva were taken from nine patients with vernal keratoconjunctivitis, seven patients with giant papillary conjunctivitis, and five control subjects. We performed a masked semiquantitative assessment of immunofluorescence on sections from each specimen. The vernal keratoconjunctivitis and giant papillary conjunctivitis groups had significantly (P less than .05) more major basic protein deposition than controls. No significant correlation between severity of disease and degree of major basic protein deposition was found. We found extracellular eosinophil granules in one of three vernal keratoconjunctivitis specimens examined by transmission electron microscopy. Thus, eosinophil degranulation commonly occurs in vernal keratoconjunctivitis and giant papillary conjunctivitis with release of eosinophil granule major basic protein and presumably other toxic granule proteins onto affected tissues. These cationic proteins are potent cytotoxins and are able to stimulate mast cell degranulation.

Number of Inflammatory Cells in the Normal Conjunctiva

We counted inflammatory cells per cubic millimeter in both the epithelium and the substantia propria of samples from upper tarsal conjunctiva of 15 normal subjects and from lower forniceal conjunctiva of ten normal subjects. The upper limit of normal for number of cells was nearly 500,000/mm3. Lymphocytes accounted for about 70% of the inflammatory cells. Neutrophils and lymphocytes were almost always present in both the epithelium and the substantia propria. Plasma cells and mast cells were present in the substantia propria of all subjects, but never in the epithelium. Neither eosinophils nor basophils were found in any specimen. We concluded that conjunctiva of the white and quiet eye usually contains heavy infiltrates of inflammatory cells.

Inflammatory changes in conjunctival scrapings after allergen provocation in humans

This study was performed to investigate the inflammatory changes occurring in the human conjunctiva at different time periods after allergen provocation. Twenty-three ryegrass-sensitive patients with allergic conjunctivitis (19 with hayfever and four with vernal conjunctivitis) were challenged by topical administration of ryegrass antigen to the eye. Allergen concentrations were increased in increments until an immediate ocular allergic reaction was elicited. Numbers of various inflammatory cells (neutrophils, eosinophils, lymphocytes, and monocytes) found in conjunctival scrapings were quantified and correlated with the clinical profile, total serum IgE, and serum IgE to Rye I antigen. Twenty minutes after some level of antigen topical challenge to the eye, all patients had ocular redness, tearing, and itching. Compared with findings in seven control subjects, significant inflammatory cells were found in the conjunctival scrapings of patients before challenge (p less than 0.05) and 20 minutes (p less than 0.001) and 6 hours (p less than 0.002) after effective challenge. Significant increases in neutrophils of patients occurred after 20 minutes (p less than 0.001), and in eosinophils at 6 hours (p less than 0.005), compared with values of control subjects. When each case was evaluated individually, nine of the 23 patients had highly evident inflammatory changes 6 hours after allergen provocation. The levels of total serum IgE and serum IgE to Rye I antigen of these nine patients did not differ significantly from the other patients in the study. Our data provide the first evidence in humans that significant inflammatory changes in conjunctival scrapings are present long after allergen exposure has ended.

Vernal Conjunctivitis and Contact Lens-Associated Giant Papillary Conjunctivitis Compared and Contrasted

We compared quantitative histologic counts of ten subjects with vernal conjunctivitis to counts of 15 subjects with contact lens-associated giant papillary conjunctivitis and to counts of 15 normal subjects. Both vernal conjunctivitis and contact lens-associated giant papillary conjunctivitis subjects had abnormalities of mast cells in the epithelium, and eosinophils and basophils in epithelium and substantia propria. No normal individuals had these abnormalities. An additional 28 subjects with ocular inflammatory conditions had tissue evaluation for abnormalities of mast cells, eosinophils, and basophils. A few eosinophils were found in four subjects. The histologic abnormalities of vernal conjunctivitis are shared by contact lens-associated giant papillary conjunctivitis but not by conjunctival inflammation in general. Vernal conjunctivitis and contact lens-associated giant papillary conjunctivitis may represent different subtypes of a general category of conjunctival abnormality characterized by giant papillae.

Ocular allergy and mast cell stabilizers.

The role of the mast cell in ocular allergy is becoming understood. As a result, the therapeutic effects of agents that stabilize the mast cell have been evaluated in the treatment of seasonal allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis. At present, cromolyn sodium is the only available mast cell stabilizer of known effectiveness. Clinical and laboratory investigations of the effectiveness of cromolyn sodium in the treatment of ocular allergy are reviewed in the present article.

Allergen dose response and late symptoms in a human model of ocular allergy

Eleven ryegrass-sensitive patients were challenged weekly for 4 weeks with incremental doses of ryegrass allergen applied topically to one eye; a buffer was applied to the other eye. A clinical examination and tear-fluid cytology were performed before challenge and at 20 minutes, 1 hour, and 6 hours after challenge. A significant clinical reaction and neutrophil accumulation in the tear film occurred at 20 minutes. At 1 hour, a clinical response and tear cytologic reaction were present only at higher antigen concentrations. Six hours after antigen challenge, only the highest allergen concentration (320,000 BU/ml) produced a clinical late-phase reaction (LPR) (p less than 0.01) and tear cytologic change (presence of eosinophils and lymphocytes). Five nonryegrass-sensitive control subjects were unresponsive to a similar challenge. These results indicate that a conjunctival response to allergen challenge is dose dependent, that is, the higher the dose, the more likely an LPR will occur and that an LPR correlates with significant numbers of inflammatory cells in the tear film.

Eosinophil Granule Major Basic Protein and Charcot-Leyden Crystal Protein in Human Tears

We measured the levels of major basic protein and Charcot-Leyden crystal protein in tears from patients with ventral keratoconjunctivitis or miscellaneous inflammatory or noninflammatory ocular conditions, and from normal subjects. Patients with vernal keratoconjunctivitis had significantly increased levels of both proteins in their tears compared with the other subjects tested; levels of major basic protein seemed to correlate with the severity of the disease. The levels of Charcot-Leyden crystal protein paralleled those of major basic proteins.

Tear Histamine Levels in Vernal Conjunctivitis and Other Ocular Inflammations

Histamine levels were measured in tears from normal volunteers (geometric mean, 5 ng/ml), patients with vernal conjunctivitis (16 ng/ml), and patients with a wide variety of external ocular inflammatory disease (3 ng/ml). Histamine levels were significantly higher in patients with vernal conjunctivitis than in normal subjects (P < 0.01) or patients with other types of ocular inflammation (P < 0.001). We postulate that histamine is an important mediator in the expression of the inflammatory response in vernal conjunctivitis, and that its elevation may be caused by abnormalities in the number of mast cells, the stability of the mast cells or in the system that regulates histamine.