Michelle A. George

Histaminase Activity in Patients with Vernal Keratoconjunctivitis

PURPOSE To investigate the activity of histamine-degradating enzymes in tears and plasma of patients with vernal keratoconjunctivitis (VKC). METHOD Tear and plasma samples were collected from patients with VKC and from age-matched control subjects. Histamine was measured by enzyme-linked immunosorbent assay in acid samples treated with perchloric to deactivate histaminase and in untreated samples. Tear cytology, skin test reactivity to histamine, and the sum clinical score of allergic signs and symptoms in patients with VKC also were evaluated. Nineteen patients with active VKC and six age-matched control subjects participated in this study. RESULTS In untreated samples, tear histamine (mean +/- standard error of the mean) was 11.15 +/- 2.16 ng/ml in patients with VKC and 0.855 +/- 0.225 ng/ml in control tears (P < 0.001). In treated samples, mean tear histamine was 22.25 +/- 4.17 ng/ml in patients with VKC versus 10.64 +/- 2.85 ng/ml in control subjects (not statistically different). The ratio of histamine in treated to untreated samples (indicating histaminase activity) was significantly lower in patients with VKC (2.30 +/- 0.263) than in control subjects (17.57 +/- 5.97; P = 0.0001). Plasma histamine levels in untreated and treated samples were significantly higher in patients with VKC (untreated, 2.23 +/- 0.334 ng/ml; treated, 4.37 +/- 0.357 ng/ml) than in control subjects (untreated, 0.254 +/- 0.068, P = 0.0002; treated, 2.96 +/- 0.171 ng/ml, P = 0.0082). The enzymatic breakdown of histamine (treated/ untreated) in plasma was significantly decreased in patients with VKC (2.54 +/- 0.447) compared with control subjects (14.78 +/- 4.86; P = 0.0012). Skin reactivity to histamine was not increased in VKC. Tear histamine levels were significantly correlated to tear lymphocyte content in the general population and to tear basophils in the patients with tarsal-vernal VKC only. An increased number of tear eosinophils were correlated with elevated enzyme activity only in patients with tarsal-vernal VKC and to the clinical score only in limbal-vernal patients. CONCLUSION The enzymatic degradation of histamine was significantly decreased in patients with VKC compared with control subjects in both tears and plasma, suggesting that this dysfunction may be a primary factor in the pathophysiology of VKC.

Evaluation of the new ophthalmic antihistamine, 0.05% levocabastine, in the clinical allergen challenge model of allergic conjunctivitis.

The objective of this study was to evaluate the efficacy of 0.05% levocabastine, a new antihistamine formulated for ophthalmic use, compared with the placebo vehicle for the treatment of allergic conjunctivitis induced by ocular allergen challenge. Subjects who reacted. positively in both eyes on two separate occasions to ocular allergen challenge with grass, ragweed, or cat dander (N = 47) received one dose of 1 to 2 drops of 0.05% levocabastine in one eye and its vehicle in the other eye. After 10 minutes, the predetermined dose of allergen was instilled in both eyes. Signs and symptoms of allergic conjunctivitis were evaluated with biomicroscopy and subjective evaluation of itching after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and reevaluated to determine levocabastines duration of action. Results showed that levocabastine was significantly more effective than placebo in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and in inhibiting all parameters except eyelid swelling after the rechallenge 4 hours later (p < 0.05). These results demonstrate that levocabastine, currently the only ophthalmic antihistamine available that is not combined with a vasoconstrictor, is efficacious in the inhibition of itching, as well as all of the allergic signs of a vascular origin, with a duration of action of at least 4 hours. Because of its strong effects on itching and hyperemia, chemosis, lid swelling, and tearing, levocabastine would be a valuable therapeutic agent to add to the heterogeneous family of antiallergic compounds presently available for the treatment of seasonal allergic conjunctivitis.

A Scanning Electron Micrographic Comparison of the Effects of Two Preservative-Free Artificial Tear Solutions on the Corneal Epithelium as Compared to a Phosphate Buffered Saline and a 0.02% Benzalkonium Chloride Control

Common ophthalmic preservatives can be divided into five classes: quaternary ammonium compounds (benzalkonium chloride), mercurials (thimerisol), alcohols (chlorobutanol), esters of parahydroxybenzoic acid, and other compounds (polymyxin and chlorhexidine).1

A Precise Method of Using Rose Bengal in the Evaluation of Dry Eye and the Detection of Changes in its Severity

Rose bengal (tetrachloro-tetraiodo fluorescein sodium) is a vital dye used to diagnose disorders of the external eye, particularly dry eye syndrome. Historically, it has been written that rose bengal possesses a propensity for dead or degenerate cells, but will also stain mucus. Differentiation between degenerate cells and mucus has been achieved by the addition of alcian blue, allowing the degenerate cells to remain red in coloring while the mucus turns blue1. Recent work performed by Feenstra and Tseng2 has suggested that rose bengal is not a vital dye, but actually absorbed by all cells in a rapid (less than 1 minute), dose dependent manner. Feenstra and Tseng further asserted that rose bengal may actually be cytotoxic, and that this effect could be augmented by exposure to light, perhaps explaining why patients complain of increased discomfort as time passes following instillation of the dye. It would appear from these results that rose bengal is not specific for degenerated cells, but instead may expose breaks in the tear film, particularly the mucin layer, exposing the underlying epithelial cells to dye absorption. While further investigation is still necessary to determine the exact mechanism of action of rose bengal, it is clear that rose bengal staining is, nevertheless, a reflection of a dry eye state. A review of the clinical use of rose bengal in diagnosing dry eye has lead to the development of a precise system in which the changes in the severity of rose bengal staining in dry eye can be mapped. As these changes have been correlated with symptomatology, they can thereby be used to evaluate the effect of specific therapies and therapeutic regimens on the severity of the condition.