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Conjunctivitis of allergic origin: clinical presentation and differential diagnosis.

Conjunctivitis of allergic origin is associated with a diversity of clinical presentations. Common features include pronounced itching, a milky conjunctival appearance, a stringy or ropy discharge and papillary hypertrophy of the tarsal conjunctiva in severe cases, and a family history of allergy. The diagnosis should be based on thorough history-taking and careful ophthalmic examination, and, when necessary, confirmation by laboratory testing. An IgE-mediated immediate hypersensitivity mechanism is associated with most types of allergic conjunctivitis, although contact allergy is mediated by lymphocytes rather than antibody. Treatment is based on the diagnosis and severity of signs and symptoms. An array of medications is available to control symptoms, and the regimen of choice should be based on the response to milder forms of therapy and consideration of drug side effects.

Conjunctivitis, Allergic↗

Sodium cromoglycate in ragweed-allergic conjunctivitis.

Sodium cromoglycate (SCG), in a 4% solution instilled into each eye 4 times daily, was compared with placebo in a double-blind, noncrossover trial in 30 matched patients with troublesome ragweed pollen-induced conjunctivitis. In the SCG group, eye symptom scores were significantly less (p = 0.05), and all patients judged that their symptoms were improved over the previous year (p less than 0.05). Less antihistamine was used by the SCG group but the difference was not significant. It was concluded that SCG was effective in the treatment of ragweed-induced seasonal allergic conjunctivitis.

Clinical Trials as Topic↗

Pollen-specific IgG antibodies in the tears of patients with allergic-like conjunctivitis.

Specific-IgG antibodies to rye grass and/or AgE in the tear secretions were demonstrated in studies of patients with the clinical features of allergic conjunctivitis but negative immediate skin reactivity and absent IgE antibodies by RAST to the inhalant pollen allergens. Studies by use of transferrin as a marker for the vascular leakage of plasma proteins into the tear secretions indicated that more than 98% of these pollen-specific IgG antibodies were locally produced by the conjunctival tissues of the external eye. These findings suggest that IgG-mediated immune mechanism(s) are important in the pathogenesis of some patients with allergic-like conjunctivitis.

Adolescent↗

Complement proteins and C3 anaphylatoxin in the tears of patients with conjunctivitis.

Previous studies in our laboratory have demonstrated pollen-specific IgG antibodies in the tears of patients with vernal conjunctivitis (VC) and elevated tear IgG levels in patients with contact lens-induced giant papillary conjunctivitis (GPC). Tear secretions were examined for complement (C) proteins to determine the role of this effector system in the pathogenesis of these ocular disorders. The tears of VC (15) and GPC (10) patients with active disease had elevated tear levels of both C3 and factor B. By use of transferrin as a marker for the leakage of plasma proteins into the tears, most C3 was locally produced by the conjunctival tissues. Although immune complexes could not be detected in the tear secretions, increased levels of C3 des Arg were present in the tears that suggested complement activation with the generation of anaphylatoxins. These studies suggest that complement may be important in the inflammatory ocular process of VC and GPC and that the generation of anaphylatoxins (C3a), even by nonimmune mechanisms, may contribute to basophil and mast cell activation with the release of inflammatory mediators into the tear secretions.

Complement C3↗

Sodium cromoglycate eye drops: regular versus "as needed" use in the treatment of seasonal allergic conjunctivitis.

OBJECTIVE: The objective of this study was to compare the efficacy and side effects of sodium cromoglycate eye drops (Opticrom 2%) used regularly versus as needed in the treatment of seasonal (ragweed) allergic conjunctivitis. METHODS: A randomized, unblinded, parallel group comparison was performed during the 6 weeks of the ragweed pollen season. Sixty-two adults with ragweed pollen-induced conjunctivitis were recruited for the study from previous ragweed studies and notices in the local media. Two drops of sodium cromoglycate were placed in each eye either four times daily (regular treatment group) or when needed, up to four times daily (prn group), from 1 week before and throughout the ragweed pollen season. Uncontrolled eye symptoms were treated with terfenadine 60 mg as needed, up to 120 mg daily. Subjects kept daily diaries for symptoms and medication requirements throughout the 6 weeks of treatment. The Rhinoconjunctivitis Quality of Life Questionnaire was administered and adverse experiences were reported after 1, 3, and 6 weeks of treatment. RESULTS: Diary eye symptoms were similar in the two treatment groups, but quality of life was better in the regular treatment group. There was a trend for the prn group to require more terfenadine for uncontrolled eye symptoms. CONCLUSIONS: There may be some additional therapeutic benefit from using sodium cromoglycate eye drops regularly throughout the ragweed pollen season.

Adolescent↗

Ciprofloxacin and levofloxacin resistance among methicillin-sensitive Staphylococcus aureus isolates from keratitis and conjunctivitis.

PURPOSE: The majority of Staphylococcus aureus isolated from ocular infections are methicillin sensitive (MSSA). Fluoroquinolone resistance among methicillin- resistant Staphylococcus aureus is well known but not among MSSA. In this study we investigate the emergence of fluoroquinolone (ciprofloxacin, levofloxacin) resistance among methicillin-sensitive Staphylococcus aureus isolates from keratitis and conjunctivitis. DESIGN: Cross-sectional study. METHODS: Minimal inhibitory concentration susceptibility profiles for 1230 S. aureus isolates from keratitis and conjunctivitis were analyzed. Historical and current rates of emerging fluoroquinolone resistance for methicillin-resistant (MRSA) and methicillin-sensitive isolates (MSSA) were evaluated. Sensitivity patterns for vancomycin and gentamicin were also documented. RESULTS: Ciprofloxacin resistance among corneal and conjunctival S. aureus isolates during the first 6 years after its introduction (baseline) (1990-1995) was 8% and ranged from 3% to 11%. The rate for the most recent 6 years (current) (1996-2001) was 20.7%. Baseline ciprofloxacin resistance for MSSA isolates was 2% vs 55.8% for MRSA. The current resistance rate for MSSA is 5% vs 83.7% for MRSA. The general resistance rate from January 2000 to December 2001 for levofloxacin was 25.5% vs 33.2% for ciprofloxacin (P =.13). The levofloxacin-resistance rate for MSSA was 4.7% vs 11.9% for ciprofloxacin (P =.05). In MRSA isolates, a higher resistance rate was found for ciprofloxacin (95.7%) vs levofloxacin (82.1%) (P =.04). No resistance for vancomycin was documented for any of the S. aureus isolates. Gentamicin susceptibility for MSSA was 99% and MRSA was 86%. CONCLUSIONS: Ciprofloxacin and levofloxacin resistance among methicillin-sensitive S. aureus corneal and conjunctival isolates is increasing. This is of concern because it narrows treatment choices for the management of these common ocular infections.

Anti-Infective Agents↗

The effects of topical ketorolac and indomethacin on measles conjunctivitis: randomized controlled trial.

PURPOSE: To compare the effect of topical ketorolac and indomethacin on measles conjunctivitis. DESIGN: Prospective double-masked placebo-controlled randomized trial. METHODS: Sixty-two patients with severe measles conjunctivitis were included in this study. All patients were hospitalized and randomly assigned to receive ketorolac 0.5% or indomethacin 0.1% in the right eye and artificial tears in the left eye. Conjunctival hyperemia, burning sensations, foreign-body sensations, and photophobia scores were conducted at baseline and at days seven and 14. A satisfaction score was evaluated at the end of the study. RESULTS: The conjunctival injection score of the control eyes was significantly higher than those of the ketorolac- and indomethacin-treated eyes at day seven (P < .05). The conjunctival injection score of the ketorolac-treated eyes was lower than that of the indomethacin-treated eyes at days seven and 14, but this did not reach statistical significance. There was no significant difference in the burning and foreign-body sensations and in the photophobia scores among the study eyes at baseline, day seven, and day 14 (P > .05). There was no significant difference in the satisfaction score among the study eyes at the end of the study (P > .05). CONCLUSIONS: In patients with measles during the first two weeks of infection, ketorolac and indomethacin were more effective than artificial tears in decreasing conjunctival hyperemia, but burning sensations, foreign-body sensations, and photophobia were unaffected.

Administration, Topical↗

TLR2 agonist ameliorates murine experimental allergic conjunctivitis by inducing CD4 positive T-cell apoptosis rather than by affecting the Th1/Th2 balance.

Innate immune responses that operate through Toll-like receptors (TLRs) are actively involved in the development of diseases predominantly mediated by adaptive immune responses. This is true also for allergic disease, as TLRs have been found to be involved in the development of allergic airway inflammation. We investigated whether stimulating TLR2 also abrogates murine allergic conjunctivitis by upregulating Th1 responses. We found that treating mice during the efferent phase with the TLR2 agonist Pam3CSK4 significantly suppressed eosinophil infiltration into the conjunctiva. However, Pam3CSK4 treatment inhibited both the Th1 and Th2 responses in the mice, and also suppressed eosinophil infiltration in IFN-gamma knockout mice. Flow cytometric analysis demonstrated that Pam3CSK4 treatment significantly elevated the numbers of annexin V-positive splenocytes, especially CD4 positive T cells. Thus, the stimulation of TLR2 during the efferent phase of murine allergic conjunctivitis suppresses eosinophil infiltration by inducing CD4 positive T-cell apoptosis rather than upregulating Th1 responses.

Animals↗

Antibodies to T-cell Ig and mucin domain-containing proteins (Tim)-1 and -3 suppress the induction and progression of murine allergic conjunctivitis.

The T cell Ig and mucin domain-containing proteins (Tim) regulate Th1- and Th2-mediated immune responses. We investigated the ability of Abs blocking Tim-1 or Tim-3 ligand-binding activity to prevent and treat murine experimental allergic conjunctivitis (EC), a Th2-mediated disease. Treatment with either Ab during the induction phase of EC in actively immunized wild-type mice suppressed EC and upregulated Th1 and Th2 immune responses. In contrast, both Abs exacerbated EC in actively immunized IFN-gamma-knockout mice. Thus, both anti-Tim Abs suppress the pathogenic immune responses generated in the induction phase by upregulating systemic IFN-gamma production. Treatment of actively immunized mice and passively immunized mice with either anti-Tim Ab just prior to RW challenge also suppressed EC. Thus, treatment with anti-Tim-1 or anti-Tim-3 Ab can suppress both the induction and progression of EC, which could indicate potential preventive and/or therapeutic approaches for allergic diseases such as allergic conjunctivitis.

Animals↗

Modulation of murine experimental allergic conjunctivitis by treatment with alpha-galactosylceramide.

When mice are treated with alpha-galactosylceramide (alpha-GalCer), NKT cells are activated and suppress the development of experimental airway inflammation. This suppressive effect is believed to be mediated by the upregulation of IFN-gamma. Here, we investigated whether alpha-GalCer treatment can also modulate the development of experimental allergic conjunctivitis (EC). EC was induced in wild-type and IFN-gamma-deficient Balb/c mice by active immunization with ragweed (RW) followed by challenge with RW in eye drops. The mice were intraperitoneally injected with alpha-GalCer or vehicle at the time of immunization or before RW challenge. Twenty-four hours after RW challenge, conjunctivas, spleens and sera were harvested for histological analysis, flow cytometric, proliferation and cytokine assays, and measurement of immunoglobulin levels, respectively. Treatment with alpha-GalCer at the time of the EC-priming immunization significantly increased Th2 responses and markedly upregulated the severity of the EC. However, treatment with alpha-GalCer just before the Ag challenge that triggers EC in primed animals significantly suppressed the disease. This was associated with an increased frequency of CD4(+)CD25(+) cells, which express Foxp3, in the spleen. alpha-GalCer treatment just prior to Ag challenge also suppressed the development of EC in IFN-gamma-deficient mice, and we found apoptosis and anergy are unlikely to play a major role in the mechanism by which pre-challenge alpha-GalCer treatment suppresses EC. These data suggest that NKT cells can play a downregulatory role in the development of EC and that alpha-GalCer may be useful for treating allergic conjunctivitis.

Allergens↗

A chronic model for evaluating the itching associated with allergic conjunctivitis in rats.

The present study was performed to develop a new model for evaluating itching associated with allergic conjunctivitis in rats. Repeated topical application of antigen caused an increase in eye scratching behavior in sensitized animals, and a significant difference was observed from days 21 to 42. Almost the same findings were observed in allergic symptoms, hyperemia and edema. Instillation of histamine also resulted in an increase in eye scratching behavior. The sensitivity to histamine in eye scratching behavior was increased by topical antigen application for 42 days after sensitization. In addition, the number of conjunctival eosinophils was significantly increased by repeated topical antigen application from days 21 to 42 in sensitized rats. Some anti-allergic drugs such as olopatadine (H1 antagonist), cetiridine (H1 antagonist) and ramatroban (thromboxane A2 (TXA2) antagonist) caused an inhibition of eye scratching behavior induced by topical sensitization in a dose-related manner. However, zafirlukast (cys-LT antagonist) caused no significant inhibition even at a dose of 30 mg/kg. The findings in present model of itching in allergic conjunctivitis were mainly through histamine H1-activity, and thromboxane A2 receptors were also involved in the response.

Animals↗

Participation of chemical mediators in the development of experimental allergic conjunctivitis in rats.

In the present study, we investigated the participation of chemical mediators in the development of experimental allergic conjunctivitis in rats. Cetirizine (a histamine H1 receptor antagonist), ramatroban (a thromboxane A2 (TXA2) receptor antagonist) and zafirlukast (a cysteinyl leukotrienes (cys-LTs) receptor antagonist) were orally administered from day 14 to day 42 during repeated topical antigen challenge. An increase in reactivity to antigen- and histamine-induced eye scratching behavior was observed by topical sensitization in sensitized rats. Although increased reactivity to antigen was not influenced by cetirizine, ramatoroban and zafirlukast, increased reactivity to histamine was significantly inhibited by ramatroban. The development of conjunctival edema was also observed for topical sensitization. Cetirizine caused no inhibition of the development of conjunctival edema, but ramatroban and zafirlukast inhibited the development of conjunctival edema. In addition, the number of eosinophils in the conjunctiva was increased by topical sensitization. Cetirizine had no significant effect on the increase in the number of eosinophils. However, ramatroban and zafirlukast were effective in inhibiting an increase in the number of eosinophils induced by topical sensitization. These results indicate that TXA2 is involved in increased histamine reactivity, and TXA2 and cys-LTs are associated with not only the conjunctival edema but also eosinophil infiltration during the development of experimental allergic conjunctivitis in rats.

Administration, Oral↗

Effect of pollen-mediated oxidative stress on immediate hypersensitivity reactions and late-phase inflammation in allergic conjunctivitis.

BACKGROUND: Allergic eye diseases are complex inflammatory conditions of the conjunctiva that are becoming increasingly prevalent and present an increasing economic burden because of direct and indirect health expenditures. OBJECTIVE: We sought to identify factors that may synergize with antigen-induced allergic inflammation and lead to allergic conjunctivitis. We used a murine model of allergic conjunctivitis to test the effect of oxidative stress generated by pollen oxidases using nicotinamide adenine dinucleotide (reduced) or nicotinamide adenine dinucleotide phosphate (reduced) (NAD[P]H) as an electron donor present in pollen grains. METHODS: Reactive oxygen species (ROS) generation by hydrated Ambrosia artemisiifolia pollen (short ragweed pollen; RWP) grains was determined by using 2'-7'-dihydro-dichlorofluorescein diacetate, nitroblue tetrazolium reduction, and Amplex Red assay. The RWP-induced changes in intracellular ROS levels were examined in A549 cells, human primary bronchial epithelial cells, and murine conjunctiva. RESULTS: Ragweed pollen grains contain NAD(P)H oxidase activity, which is diphenyleneiodonium-sensitive and quinacrine-sensitive and sodium azide-resistant. These NAD(P)H oxidases generate a superoxide anion that can be converted to H2O2 by pollen grain-associated superoxide dismutase. These diffusible oxygen radicals from pollen grains increase intracellular ROS levels in cultured epithelial cells and murine conjunctiva. Similar phenomena were observed in sensitized and naive mice, indicating that the RWP-induced oxidative stress in conjunctival epithelium is independent of adaptive immunity. Inactivation of NAD(P)H oxidase activity in RWP decreases the immediate-type hypersensitivity and inflammatory cell infiltration into the conjunctiva. CONCLUSION: Our data suggest that ROS generated by NAD(P)H oxidases in pollen grains intensify immediate allergic reactions and recruitment of inflammatory cells in murine conjunctiva.

Animals↗

Towards an in vitro model for acute hemorrhagic conjunctivitis: cytokine-mediated vascular endothelial cell activation triggered by enterovirus type 70 infection.

BACKGROUND: Little is known of the pathogenetic mechanisms of enterovirus type 70 (EV70), a causative agent of acute hemorrhagic conjunctivitis. However, virus- or cytokine-induced perturbation of vascular endothelial cells are potential triggering events. OBJECTIVE: To determine whether EV70 infection of human umbilical vascular endothelial cells (HUVECs) and human corneal epithelial cells (HCEs) causes the release of vasoactive cytokines, capable of triggering vascular endothelial cell activation. STUDY DESIGN: Susceptibility of cultured HUVECs and HCEs to EV70 was tested by observing the appearance of cytopathic effect or immunoprecipitation of viral protein in infected cells. The culture fluids from the virus-infected cells were tested for their ability to stimulate the expression of intercellular adhesion molecule-1 (ICAM-1) on uninfected HUVECs. Anti-cytokine antibodies were used to identify ICAM-1-activating cytokine(s). RESULTS: Both HUVECs and HCEs were susceptible to EV70 infection. Culture fluids from EV70-infected HUVECs and HCEs stimulated ICAM-l expression on uninfected HUVECs, which was completely blocked by anti-interleukin-1alpha (IL-1alpha) antibody but not by interleukin-1beta (IL-1beta) or anti-tumor necrosis factor alpha (TNFalpha) antibodies. CONCLUSION: This study provides the first evidence of EV70 infection of both HCEs and HUVECs, and furthermore, identifies IL-1alpha as the predominant endothelial cell-activating factor produced by EV70-infected cells. Since endothelial cell activation is often an initiating step towards vascular permeability and/or inflammation, the perturbation of endothelial cell function through EV70 induced IL-1alpha is thus a potential contributory factor in the pathogenesis of EV70-associated hemorrhagic conjunctivitis.

Antibodies↗

[Identification of adenoviruses serotypes implicated in haemorrhagic conjunctivitis in Tunisia].

Human adenoviruses (ADV) are distributed worldwide; they are associated with a variety of diseases. Some ADV can be implicated in large epidemics of conjunctivitis, gastroenteritis and respiratory infections. Classical diagnosis of ADV infections is based on virus isolation on cell culture and identification of the serotype by neutralization test or hemagglutination inhibition assay. However, these methods have a lack of rapidity that makes them impractical in clinical situations. With the advent of PCR, the diagnosis of ADV was improved. In this work, we have used molecular techniques for the identification of ADV serotypes implicated in conjunctivitis in Tunisia. A total of 199 conjunctival swabs received between October 2000 and May 2005 were investigated. Serotype identification was performed using a PCR followed by restriction enzyme analysis in the hexon gene. Typing by sequencing of the PCR product was used to confirm the serotype identification. Among the 199 tested clinical specimens, 24% were positive for ADV. Two different profiles were observed: one predominant corresponding to the majority of the detected ADV; this profile is in favour of two distinct serotypes, ADV37 or ADV8; the second profile was specific of ADV4 and was found in one case observed in 2005. Sequencing confirmed two serotypes: ADV8 with an endemoepidemically circulation in our country and ADV4 that appeared sporadic. The present work showed the importance of molecular techniques not only for ADV detection but also for identification of the circulating serotypes. These techniques are practical and interesting mainly for the rapid virological investigation during epidemics.

Adenoviridae↗

Clinical safety of moxifloxacin ophthalmic solution 0.5% (VIGAMOX) in pediatric and nonpediatric patients with bacterial conjunctivitis.

Five independent, multicentered, double-masked, parallel, controlled studies were conducted to determine the safety of moxifloxacin ophthalmic solution 0.5% (VIGAMOX) in pediatric and nonpediatric patients with bacterial conjunctivitis. Patients were randomized into one of two treatment groups in each study and received either moxifloxacin ophthalmic solution 0.5% b.i.d. or t.i.d. or a comparator. A total of 1,978 patients (918 pediatric and 1,060 nonpediatric) was evaluable for safety. The most frequent adverse event in the overall safety population was transient ocular discomfort, occurring at an incidence of 2.8%, which was similar to that observed with the vehicle. No treatment-related changes in ocular signs or visual acuity were observed with moxifloxacin ophthalmic solution 0.5%, except for one clinically relevant change in visual acuity. Thus, based upon a review of adverse events and an assessment of ocular parameters, moxifloxacin ophthalmic solution 0.5% formulated without the preservative, benzalkonium chloride, is safe and well tolerated in pediatric (3 days-17 years of age) and nonpediatric (18-93 years) patients with bacterial conjunctivitis.

Adult↗

Chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and fatal Wegener granulomatosis.

PURPOSE: To describe a case of chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and Wegener granulomatosis. METHODS: Observational case report. A retrospective study. RESULTS: An 80-year-old man presented with chronic cicatrizing conjunctivitis, peripheral corneal thinning, and Wegener granulomatosis, which were diagnosed by his referring physician based on clinical (recurrent epistaxis, sinus congestion) and histopathologic features of nasal mucosa (granulomatous inflammation, vasculitis). A conjunctival biopsy performed by us disclosed features of active Wegener granulomatosis and ocular cicatricial pemphigoid, which indicate lack of control of both diseases with methotrexate treatment. The patient died of pulmonary complications from Wegener granulomatosis 1 week after our evaluation. CONCLUSION: Ocular cicatricial pemphigoid and Wegener granulomatosis are both potentially fatal autoimmune diseases. Ocular involvement in Wegener granulomatosis indicates poor control of the underlying systemic condition and is a marker for active vasculitis, which indicates the need for treatment with cyclophosphamide.

Aged↗

Porphyria cutanea tarda presenting as cicatricial conjunctivitis.

PURPOSE: To report a case of porphyria cutanea tarda presenting as cicatricial conjunctivitis. DESIGN: Observational study. METHODS: A 31-year-old man presented with bilateral inferior symblepharon, superior tarsal conjunctival scarring and concretions, and recurrent conjunctival and episcleral injection. RESULTS: Four years after initial presentation, the patient developed hepatitis C, and 2 years later blisters on his scalp and hands. Direct immunofluorescence studies of biopsies taken from the palpebral conjunctiva of the right lower lid were negative for cicatricial pemphigoid. A twenty-four hour urine specimen analysis revealed elevated levels of uroporphyrins and polycarboxylated porphyrins, confirming the diagnosis of porphyria cutanea tarda. The patient was treated with repeated phlebotomies and oral hydroxychloroquine, which resulted in a significant decrease in the skin lesions, conjunctival injection, and concretions under the upper lids. CONCLUSIONS: Cicatricial conjunctivitis may be a manifestation of porphyria cutanea tarda.

Administration, Oral↗