Allergic conjunctivitis: a cross-sectional study.

BACKGROUND: Ocular allergy is a common disease in daily practice. OBJECTIVES: A cross-sectional study was conducted to evaluate clinical aspects of and therapeutic approaches to ocular allergy in Italy. METHODS: Of the 3685 patients affected by ocular allergy and enrolled by 304 ophthalmologists nationally, 3545 were eligible to be included in the statistical analysis. A questionnaire was administered in office to record demographic data, comorbidities, trigger factors, number of conjunctivitis episodes, and past treatments. Signs and symptoms were graded according to their severity, frequency, and duration. RESULTS: Mean age of enrolled patients was 38 ± 19 years. Seasonal allergic conjunctivitis (55% of patients) was equally distributed among the different age groups, while perennial allergic conjunctivitis (18%) increased with age and vernal keratoconjunctivitis (9%) was more frequent under the age of 18. Itching and redness were reported in 90% and 85%, respectively; lid skin involvement was observed in 22% of cases and keratitis in 11%. Pollen sensitivities were indicated as the most frequent triggers; however, exposure to non-specific environmental conditions, pollutants, and cigarette smoke was frequently reported. Only 35% of patients underwent a diagnostic evaluation of specific allergic sensitization, with positive allergy tests found in 82% of this subset. With regard to treatment, topical decongestants were used in 43% of patients, corticosteroids in 41%, antihistamines in 29%, systemic antihistamines in 27%, and mast cell stabilizers in 15%. CONCLUSION: This survey provided useful epidemiological information regarding the clinical characteristics and treatment options of a large cohort of patients affected by different forms of ocular allergy. CLINICAL RELEVANCE: An understanding of ocular allergic disease, its incidence, demographics, and treatment paradigms provides important information towards understanding its pharmacoeconomics and burden on the national health system.

Peripapillary fundus perimetry in eyes with glaucoma.

AIMS: To evaluate, with fundus perimetry, the peripapillary differential light threshold (DLT) in eyes with glaucoma and ocular hypertension (OHT), and compare it with peripapillary retinal nerve fibre layer (RNFL) thickness. METHODS: 35 glaucomatous, 29 OHT and 24 control eyes were included. Peripapillary DLT at 1 degrees from the optic nerve head was quantified with fundus perimetry; peripapillary RNFL thickness was measured over the same area by optical coherence tomography. RESULTS: Mean (SD) peripapillary DLT was 19.2 (1.7), 17.6 (4.2) and 10.1 (6.9) dB in control, OHT and glaucomatous eyes, respectively (p<0.001). Mean (SD) RNFL thickness was 98.4 (35.3), 83.9 (35.1) and 55.8 (28.2) microm, respectively (p<0.001). Mean peripapillary DLT showed higher sensitivity and specificity in differentiating the three groups compared with RNFL thickness. CONCLUSION: Progressive, significant reduction of peripapillary DLT was documented in OHT and glaucomatous eyes compared with controls (p<0.001). DLT reduction parallels RNFL reduction.

HNK-1+ (Leu-7) and other lymphocyte subsets in long-term survivors with renal allotransplants.

At 5 or more years after renal transplantation, 42 patients were studied for their lymphocyte subsets to Leu-1, Leu-2, Leu-3, and Leu-7. It was found that, in this group of patients who ranged from 25 to 60 years of age, there was a significant decrease in the number of T helper cells and a decrease in the absolute level of T lymphocytes, with no significant change in the number of T suppressor cells. On a relative basis, the helper/suppressor ratio was decreased in patients when compared with normal persons. This was due to an increase in the relative numbers of suppressor cells. It was demonstrated that the Leu-7+ subset, which marks the NK population, was significantly elevated, in relative proportion, in peripheral blood when compared with controls. This was not seen on an absolute basis. The age-dependence of the relative numbers of Leu-7+ cells was seen in the normal control population and in the transplant cohort. There was no significant correlation between lymphocyte subset measurements and delayed-type hypersensitivity skin tests in the transplant population. A finding of interest is that 6 of the patients who had been treated for malignant disease during their posttransplant course had significantly higher numbers of Leu-7+ cells on a relative basis. In 5 of these patients, for whom data was available on absolute numbers, there was also a highly significant difference in the absolute numbers of Leu-7+ cells in these treated and surviving allograft recipients. It is speculated that this finding may suggest that an increase in Leu-7+ cells marks posttransplant patients who have a successful outcome following the treatment of malignancy, for which they are at increased risk.

Effects of cyclosporin A on human conjunctival fibroblasts.

OBJECTIVE: To evaluate the effects of cyclosporin A (CsA) on cytokine and/or collagen production, cell growth, and apoptosis in conjunctival fibroblast cultures. METHODS: Fibroblast cultures derived from normal subjects and patients with vernal keratoconjunctivitis and pemphigoid were exposed to different concentrations of CsA for either 24 hours or 30 days. The effects were evaluated by the colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) test to assess cell proliferation, and by the measurement of procollagen I (PIP) and procollagen III (PIIIP) cytokines and total protein in culture medium. CsA-induced apoptosis was assessed by fluorescence-activated cell sorter analysis. RESULTS: After 24 hours of exposure to doses of CsA of more than 10 microg/mL, cell proliferation and migration were significantly reduced. Cyclosporin A reduced PIP and interleukin 1 (IL-1) production in a dose-dependent manner. Interleukin 6 and IL-8 were increased by 10 microg/mL of CsA, whereas transforming growth factor beta, PIIIP, and total protein were unaffected. Cyclosporin A exposure induced apoptosis in a time- and dose-dependent manner. Long-term exposure to CsA reduced IL-6 but did not modify PIIIP production. CONCLUSION: Exposure to CsA directly modified fibroblast behavior. CLINICAL RELEVANCE: Cyclosporin A ability to accelerate apoptosis in clinically fibrotic tissues may prove to be therapeutic and useful in hyperproliferative conjunctival disorders.

Lysophosphatidyl choline in the aqueous humour during ocular inflammation.

Phospholipase A and lysophosphatidyl choline (LPC) have been shown to induce significant changes in the lens permeability in vitro to cations and soluble proteins. During uveal inflammation, in various experimental models and in man as well, the levels of LPC in the aqueous humour have been shown to reach values which are harmful to the lens in vitro. In addition, a phospholipase is thought to be activated during the antigen + antibody + complement sequence. The possible significance of these findings is discussed in relation to the pathogenesis of complicated cataracts in uveitis and the possible role of the lens as a source of autoantigens in recurrent uveitis.

Anti-inflammatory and antiallergic effects of ketorolac tromethamine in the conjunctival provocation model.

AIM: To study the effect of the topical anti-inflammatory drug, ketorolac, on (1) the clinical allergic reaction induced by the conjunctival provocation test (CPT); (2) the release of tryptase in tears; and (3) the expression of adhesion molecules on the conjunctival epithelium. METHODS: 10 allergic but non-active patients were challenged in both eyes with increasing doses of specific allergen to obtain a positive bilateral reaction and rechallenged, after 1 week, to confirm the allergic threshold dose response. After 2 weeks, a third CPT was then performed bilaterally 30 minutes after topical application of ketorolac in one eye and placebo in the contralateral eye in a double blind fashion. Clinical symptoms and signs were registered 5, 10, 15, and 20 minutes after challenge. The following objective tests were performed: tear tryptase measurement; tear cytology; and conjunctival impression cytology for immunohistochemical expression of ICAM-1 on epithelial cells. RESULTS: Compared with placebo, ketorolac significantly reduced the total clinical score and the itching score in the 20 minutes after challenge (p<0.0005). Tear levels of tryptase were significantly reduced in the ketorolac pretreated eyes compared with placebo (p<0.03). Eosinophils, neutrophils, and lymphocytes in tear cytology were significantly lower in ketorolac treated eyes compared with placebo. A significant difference in the epithelial expression of ICAM-1 was observed between placebo and ketorolac treated eyes (p<0.05). CONCLUSION: Ketorolac proved to be effective in reducing mast cell degranulation, as indicated by significantly decreased tryptase tear levels, as well as the clinical and cytological allergic reaction.

Histopathology and ultrastructure of rabbit lenses exposed 'in vitro' to lysophosphatidylcholine (LPC).

Permeability changes which take place in the lens in the course of uveitis are probably due to 'Lens Permeability Factors' present in the inflammatory aqueous. One of these 'factors', lysophosphatidyl-choline (LPC), has been shown to damage the lens in vitro: a leakage of Rb(86) and proteins, and an increase of Na(+) and water content indicate a dose-related membrane lytic effect. Damaging levels of LPC (up to 10µg/ml of aqueous humor) were found in the anterior chamber of inflamed eyes in the course of experimental uveitis in rabbits, and also in humans during uveitis. This report deals with an ultrastructural investigation on the damaging effect of different concentrations of LPC on rabbit lenses in culture. Concentrations of LPC higher than 12µg/ml caused signs of degeneration immediately below the capsule. Scanning electron microscopy revealed grossly enlarged lens fibers, globular structures of different size and widespread water vacuoles. Transmission electron microscopy showed inter- and intracellular changes in the epithelium and the outer cortex, swollen lens epithelial cells, fiber cells separation, vacuoles, and areas of decreased electron density. The overall structure of the lens fibers in the inner cortex and in the nucleus was always intact.

Tear histamine and histaminase during the early (EPR) and late (LPR) phases of the allergic reaction and the effects of lodoxamide.

The objectives of this study were two-fold: to identify tear histamine content and its relationship to changes in tear histaminase activity during the early (EPR) and late phases (LPR) of the allergic reaction induced by a conjunctival provocation test (CPT) and to evaluate the effects of lodoxamide on histamine release and allergic signs and symptoms during EPR and LPR. A baseline CPT was administered to 20 allergic patients with no baseline signs or symptoms of allergy. Clinical signs and symptoms were evaluated after 20 minutes and 6 hours. Tear samples were taken after 5-10 minutes and after 6 hours for subsequent analyses of cytology and histamine content (ELISA). Patients were then randomly assigned to receive lodoxamide or placebo four times daily for one week in a double-masked fashion. A second CPT was done after this therapy and the same parameters were re-evaluated. During EPR, tear histamine increased significantly with respect to baseline values (p < 0.05). During LPR, tear histamine increased significantly (p < 0.05) only in histamine inactivated samples. Histaminase enzymes were also significantly less active during the EPR (5.5 +/- 0.7) than the LPR (9.9 +/- 2.3) and at baseline. Histamine levels significantly correlated with allergic signs and symptoms (p < 0.05) only during the EPR. Lodoxamide significantly reduced histamine release during EPR (p < 0.05), allergic signs and symptoms during both EPR (p < 0.001) and LPR (p < 0.005), and tear cytology counts during LPR. In conclusion, greater histaminase activity may account for the smaller amount of tear histamine generally found during LPR, while these enzymes seem to play less of a role during the surge of histamine release and activity in the EPR. Lodoxamide was shown to ideally inhibit various aspects of the allergic reaction: clinical signs and symptoms in both the early and late phases, the primarily EPR-related peak of histamine release, and the primarily LPR-related changes in tear cytology.

[Specific IgE in the gastric and duodenal mucosa. An epiphenomenon or pathogenetic mechanism of some forms of "peptic" ulcer?]. / IgE specifiche nella mucosa gastrica e duodenale. Epifenomeno o meccanismo patogenetico di alcune forme di ulcera "peptica"?

Allergic mechanisms have been shown to induce gastric and intestinal damage in animal models. It has been demonstrated that people allergic to food may complain of gastrointestinal disorders. Furthermore food allergens can induce gastric mucosal damage in sensitized people. Little is known as regards allergic mechanisms underlying "peptic" ulcers although there are reports suggesting that some forms of gastric and duodenal ulcer may be caused by allergy. AIM. Of the study was to evidence if IgE specific to food and inhalants are localized in gastric and duodenal mucosa and if the in vitro incubation of gastric and duodenal biopsies with specific allergens, stimulate mast-cell mediators. MATERIALS AND METHODS. Twenty-one patients affected by gastric/duodenal ulcers (14 with high total IgE serum levels) and 16 controls were studied. All patients were submitted to upper digestive endoscopy and biopsies were taken from gastric fundus, body and antrum and duodenal bulb. Specific IgE to food and inhalant allergens were tested after homogenization of biopsies, using commercial kits. In 3 selected patients, 3 biopsies from gastric fundus and 3 from duodenal bulb were taken. After incubation of mucosal of mucosal biopsies with allergens (wheat, lactoalbumin, Parietaria J. pollen), the release of histamine and tryptase was measured. The release of Pepsinogen A was measured in the same conditions, as control. RESULTS. Specific IgE to food and inhalants allergens have been found in 164/586 tests (27.9%) of "peptic" ulcer patients and in 17/430 tests (4%) of controls. The duodenal bulb resulted the site in which most frequently IgE have been found. The release of histamine and tryptase has been stimulated only in 1/6 tests by incubation of biopsies with specific allergens in patients with specific IgE. PG-A release has been always stimulated by incubation of gastric biopsies, but not duodenal biopsies, with all tested allergens. DISCUSSION AND CONCLUSION. Specific IgE may be localized in gastric and duodenal mucosa of patients with "peptic" ulcer and/or food allergy. This event is linked to high total IgE serum levels and in a lesser extent, intestinal parasitosis, it is not strictly correlated with specific IgE in the serum and it regards both food and inhalant allergens. No relevant effects were observed after incubation of specific allergens with gastric or duodenal mucosa biopsies containing specific IgE. The possibility that higher allergens concentration stimulate mediator release from mast cells should be investigated. A defect of the gastric or duodenal epithelial barrier which permit a passage way for proteins with subsequent IgE production in the submucosa, appears to be the cause of localization of specific IgE in stomach and duodenum.

Clinical and biological efficacy of preservative-free NAAGA eye-drops versus levocabastine eye-drops in vernal keratoconjunctivitis patients.

AIMS: This comparative and randomised pilot study assessed the clinical and biological efficacy of Naaxia Sine(R) eye-drops versus levocabastine eye-drops in the treatment of vernal keratoconjunctivitis (VKC). METHODS: Twenty-three VKC patients were randomised and treated bilaterally for 28 days with N-acetyl-aspartyl-glutamate (NAAGA) or levocabastine (LEVO) eye-drops. The primary efficacy variable, overall evolution of eosinophil cationic protein (ECP) tear concentrations, was assessed in a masked fashion on D0, D7 and D28. Clinical symptoms and signs were reported at the same time points. Biological parameters were analysed with a non-parametric rank-based approach. Global tolerance was assessed by the investigator and patient. RESULTS: At all time points, ECP tear levels were significantly reduced in the NAAGA compared with the LEVO group (p = 0.023). Reduction of eosinophil leucocytes and tear lymphocytes was higher not significant in the NAAGA group. The same trend was observed for the evolution of total ocular symptom score. There were no significant differences between treatment groups in the occurrence of adverse effects, except for burning which was more frequent in the LEVO group (p = 0.002). CONCLUSION: The anti-eosinophilic actions of NAAGA were shown by a significant reduction of ECP tear concentrations. A decreased lymphocyte count and an overall improvement of the symptomatology were also noted. Moreover, the tolerability of NAAGA appeared to be better.

The effect on the macular function of laser photocoagulation for diabetic macular edema.

The benefit of focal and grid-laser photocoagulation in reducing the risk of visual loss from diabetic macular edema has been established. In order to investigate the effect of this treatment on macular function, 30 diabetics with macular edema and 1.0 visual acuity were tested before and after laser treatment at intervals of 1 week, and 1 and 3 months, respectively. The test was carried out by means of nyctometry, contrast sensitivity, hue discrimination and critical flicker frequency of blue cones. All patients had abnormal results in macular tests before treatment. During the follow-up, visual acuity remained stable and the macular tests did not statistically modify, except for nyctometry, which deteriorated at the 1-week follow-up (P = 0.02) and then increased to the basal values, and contrast sensitivity [improved at the last control (P = 0.006)]. Clinical regression of macular edema was observed, but macular function tests never normalized. Patients with diabetic macular edema and good visual acuity should be monitored with many functional methods, and laser treatment should be performed before macular function deteriorates irreversibly.

Immunopathology of the lens. II. 86Rb efflux and protein leakage from normal lenses exposed to antilens and antiuveoretina antibodies.

Normal rabbit lenses exposed in vitro to heterologous antilens and antiuveoretina antibodies lose control of the intracellular 86Rb and this effect is followed by a late leakage of lenticular proteins; both phenomena take place only in the presence of complement. This antibody-induced complement-dependent membrane damage might be involved in the pathogenesis of complicated cataracts in uveitis and in the self-maintenance of recurrent uveal inflammations.

Immunopathology of the Lens. III. The effect of experimental allergic uveitis on the cation balance in the lens.

Rabbit lenses from eyes suffering from experimental allergic uveitis showed a clear enhancement in the 86Rb efflux as compared to the lenses from the fellow normal eyes. Intracellular K+ was also significantly decreased and Na+ significantly increased after several relapses of inflammation.

Immunopathology of the lens. I 86Rb efflux and protein leakage from normal lenses exposed to unrelated antigen-antibody interactions.

Normal rabbit lenses exposed in vitro to heterologous antibody (Ab)--antigen (Ag) interactions lose control of the intracellular 86Rb; this membrane damage, which seems to be related to the quantitative ratio Ab/Ag, is relatively complement independent and is followed by a subsequent leakage of lenticular proteins. A possible implication of these findings in the development of complicated cataracts in uveitis (as 'permeability cataracts') and in the self-maintenance of recurrent uveal inflammation is shortly discussed.

Correlation between conjunctival provocation test (CPT) and systemic allergometric tests in allergic conjunctivitis.

In order to assess the potential usefulness of CPT as a diagnostic tool for ocular allergy, the correlation between skin/RAST tests and CPT was determined in 144 patients affected by allergic 'hay fever' type conjunctivitis. The results showed that an agreement between skin/RAST tests and CPT occurred in 71% of the cases (130/183). Of the 29% uncorrelated cases, 23% (43/183) were positive for at least one specific antigen by skin/RAST tests but not by CPT, while 6% (10/183) were positive for at least one specific antigen by CPT, but not by skin/RAST tests. CPT dramatically increased the histamine levels in tears (p less than 0.001). These findings show that (1) systemic tests can be misleading in that they may suggest a specific sensitisation which, in fact, does not involve the conjunctiva (systemic test positive/CPT negative); (2) CPT can identify local conjunctival sensitisation in the absence of a systemic sensitisation (systemic test negative/CPT positive); (3) CPT can demonstrate that allergic 'hay fever' type conjunctivitis may be related to allergens different from those responsible for a systemic sensitisation.

Heterogeneity of lymphocytes from aqueous humor of patients with uveitis.

T lymphocyte subsets from inflammatory aqueous humor (n = 34) have shown one of three different patterns: group 1 = lower CD4+/CD8+ ratio in aqueous as compared to peripheral blood (0.43 +/- 0.25 vs. 1.96 +/- 0.82; n = 9); group 2 = similar CD4+/CD8+ ratio in aqueous and peripheral blood (1.76 +/- 0.60 vs. 1.60 +/- 0.62; n = 22); and group 3 = higher CD4+/CD8+ ratio in aqueous as compared to peripheral blood (7.53 +/- 0.47 vs. 2.13 +/- 0.55; n = 3). DR+ T lymphocytes were significantly higher, and natural killer cells significantly lower, in inflammatory aqueous as compared to peripheral blood.

Histamine effects on conjunctival fibroblasts from patients with vernal conjunctivitis.

Histamine, an important mast cell mediator in allergic disorders, may affect extracellular matrix production and cell growth in vernal keratoconjunctivitis (VKC). In the present study, the histamine reactivity of conjunctival fibroblasts derived from VKC patients was investigated in vitro. Conjunctival fibroblast cultures were derived from biopses of 8 tarsal VKC patients and 5 normal subjects. These cells were maintained in vitro and stimulated with different concentrations of histamine with and without H1 (clorpheniramine) and H2 (cimetidine) receptor antagonists. Comparisons were made to fibroblasts grown in the same media without histamine and to fibroblasts stimulated with just antihistamine. The effects of histamine were evaluated by: (1) the MTT test to assess cell proliferation; (2) an in vitro wound model for cell migration and (3) the measurement of procollagen I (PIP) and procollagen III (PIIIP) in supernatants for collagen production. Results showed: (1) While VKC-derived fibroblasts proliferated at a faster rate than normal cells in unstimulated media, after histamine stimulation, VKC and normal cells grew at a similar rate. Both H1 and H2 antagonists significantly inhibited (P<0.05) histamine-induced cell proliferation. (2) Histamine enhanced cell migration after wounding; this effect was inhibited only by H2 antagonism. (3) When stimulated with histamine, VKC fibroblasts produced significantly more PIP than those in control media. Furthermore, VKC-derived fibroblasts were more sensitive to histamine challenge, producing significantly more PIP than normal fibroblasts. H1 and H2 antagonists did not modify histamine-stimulated PIP production. The enhanced proliferative and productive capacity of VKC fibroblasts may be the result of a selective overgrowth of one or more fibroblast subpopulations in a chronically inflamed tissue. Histamine increased proliferation, migration and collagen production in both normal and VKC fibroblasts. Since H2 antagonism modulated both cell growth and migration, but not histamine-induced collagen production, the latter may be mediated by a different receptor. These results showed that histamine is at least partially responsible for fibroblast stimulation.

Antigen sensitivity evaluated by tear-specific and serum-specific IgE, skin tests, and conjunctival and nasal provocation tests in patients with ocular allergic disease.

The potential for ocular allergic patients to have a site-specific antigen sensitisation was investigated using various diagnostic tests of allergen sensitivity in subjects with allergic conjunctivitis (AC: n = 135), vernal keratoconjunctivitis (VK: n = 20), rhinoconjunctivitis (n = 20) or rhinitis (N = 10). In the AC and VK patients, skin tests and conjunctival provocation tests (CPT) were performed, and the levels of specific IgE in serum and in tears were identified. A subgroup of 36 patients was also challenged with a nasal-specific provocation test (NPT). Results showed a poor correlation between skin test results and tear-specific IgE, and also between serum-specific IgE and tear-specific IgE in both AC and VK patients (K < 0.3). CPT and tear IgE were significantly correlated (K = 0.5) in the ocular allergic population. In patients with rhinoconjunctivitis or rhinitis, and in 10 normal subjects, results of CPT and NPT were in 100% agreement. Conversely, in patients with only conjunctivitis, little correlation was found between the results of CPT and NPT (K = 0.3). Tear-specific IgE was the only positive diagnostic sign of antigen sensitivity in 35% of VK patients and 30% of AC patients. These results suggest that the conjunctiva can be a uniquely sensitised target organ in allergic patients.

Clinical-economic audit of electrophysiologic examinations in ophthalmology.

To assess the diagnostic efficiency and direct costs of electrophysiologic tests, times and clinical data (admittance, diagnosis, final diagnosis and clinical reports) of 144 patients were recorded and statistically analyzed. Capital outlay on equipment and personnel costs were also evaluated to determine the economic impact of the tests. Electrophysiologic tests were found to play an important role in diagnosis and choice of therapy. It is important to improve collaboration between the referring ophthalmologist and the electrophysiology staff to inform patients better and to optimize the cost-benefit standards of the service. The current reimbursement by the Regional Public Health Service underestimates the costs of electrophysiologic tests.

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.