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Roles of CD4+CD25+ T cells in the development of experimental murine allergic conjunctivitis.

BACKGROUND: CD25+ regulatory T (T reg) cells play a suppressive role in experimental autoimmune uveoretinitis as well as experimental airway inflammation but their involvement in the development of allergic conjunctivitis (AC) remains unclear. We therefore investigated whether T reg cells play a role in the development of experimental AC (EC). METHODS: BALB/c and C57BL/6 mice were actively immunized with ragweed (RW). The mice were treated with an anti-CD25 Ab (PC61) or control normal rat IgG (nrIgG) either 2 days prior to active immunization or during the induction phase (days 0, 2, 4, 6 and 8). Ten days after active immunization, the mice were challenged with RW-containing drops. Twenty-four hours after the challenge, the conjunctivas were harvested for histological analysis of eosinophil infiltration, and the spleens were harvested for cell culture for splenocyte transfer. Cultured splenocytes were transferred into syngeneic mice, and 4 days after the transfer, the recipient mice were challenged with RW. Twenty-four hours after the challenge, conjunctivas were collected for histological analysis. RESULTS: Pretreatment with PC61 did not affect EC in either strain of mice; however, treatment with PC61 during the induction phase significantly suppressed EC in C57BL/6 mice. In contrast, transfer of RW-primed splenocytes from mice treated with PC61 induced EC that was significantly more severe regardless of strain and treatment protocol. CONCLUSIONS: The finding that T reg cells play a suppressive role in the development of EC in splenocyte transfer experiments suggests that modulation of T reg cells may be a possible therapy for AC.

Adoptive Transfer↗

An epidemic of acute haemorrhagic conjunctivitis caused by enterovirus 70 in Okinawa, Japan, in 1994.

BACKGROUND: Although enterovirus 70 (EV70) has been identified as the major aetiological agent of acute haemorrhagic conjunctivities (ACH),no EV70 strain has been isolated by cell culture method since 1988. Therefore, recent clinical and epidemiological characteristics of AHC caused by EV70 have not been clarified. METHODS: Clinical and serological studies were carried out on patients during the AHC epidemic in Okinawa, Japan, in 1994 in which 7509 cases were reported by national epidemiological surveillance. EV70 was confirmed as the causative agent by reverse-transcription polymerase chain reaction. RESULTS: The 11-15 years age group contained the highest number of cases (62% of the total). Conjunctival hyperaemia was present in all patients, and subconjunctival haemorrhage, superficial punctate keratitis and preauricular lymphadenopathy were present in 24.0%, 11.7% and 9.3% of AHC cases, respectively. No neurological complication was observed in this epidemic. Out of 31 paired serum samples, 10 pairs showed a fourfold rise in antibody level to EV70. None of the paired serum samples showed a fourfold rise in antibody level to Coxsackie A24 variant virus. CONCLUSION: These findings demonstrate that the clinical features of AHC observed in this study were milder than those reported previously, in contrast to the high transmission rate during an epidemic. Changes in clinical features of AHC, such as a low incidence of subconjunctival haemorrhage and disappearance of neurological complications, might be due to biological transformation of EV70. It should be noted that EV70 is still an important aetiological agent of explosive epidemics of AHC.

Adolescent↗

Ocular surface changes induced by topical application of latanoprost and timolol: a short-term study in glaucomatous patients with and without allergic conjunctivitis.

BACKGROUND: This study evaluated the conjunctival effects of latanoprost and timolol, both of which contain benzalkonium chloride, in patients with primary open-angle glaucoma (POAG), with and without a history of allergic conjunctivitis (AC). METHODS: Two groups of 25 patients with and without a positive history for AC were studied. After a 21-day wash-out period patients were randomized to 14 days treatment with latanoprost or with timolol, in a cross-over fashion. The following parameters were evaluated on days 0 and 14: number of white blood cells, ferning test, conjunctival impression cytology, subjective symptoms, and objective ocular changes. RESULTS: Latanoprost caused: (a) an increase in eosinophils in both groups and reduction in lymphocytes only in the group with a history of AC; (b) alterations in ferning test and impression cytology only in AC patients; and (c) development of subjective symptoms and objective signs only in non-AC glaucomatous subjects. Timolol therapy was responsible only for the occurrence of subjective symptoms and objective signs in non-AC patients. CONCLUSION: Latanoprost treatment induces ocular surface changes which are more evident in POAG patients who are also affected by AC. These findings are probably related to the very high latanoprost concentration of benzalkonium chloride and to its bedtime administration, which further amplifies the toxicity.

Administration, Topical↗

Expression of beta defensins in ocular surface tissue of experimentally developed allergic conjunctivitis mouse model.

PURPOSE: To investigate the expression of beta-defensin in the ocular surface of a mouse experimental allergic conjunctivitis (EAC) model. METHODS: Mouse beta-defensin (mBD)-1 and -2 mRNA expressed in conjunctival tissue of both the EAC and the control group were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. mBD-1 and mBD-2 mRNA expressed in cornea, limbus, and conjunctival epithelium of the EAC and the control group were also analyzed using a laser-assisted microdissection technique and the RT-PCR method. RESULTS: There was no significant difference in the amount of mBD-1 between the EAC and the control group. However, the EAC group had significantly less mBD-2 (0.23 +/- 0.15 x 10(4) copy/microl) than the control group (3.61 +/- 4.87 x 10(4) copy/microl) (P < 0.01, Mann-Whitney U test). mBD-1 mRNA was positive for all examined tissue in both groups. The expression of mBD-2 mRNA in the EAC group was definitely positive for the corneal and conjunctival epithelium and negative for the limbus. CONCLUSION: mBD-2 mRNA was expressed significantly less in the EAC model than in the control. Analysis by site in the ocular surface tissue revealed that this reduction was caused by the diminished expression of mBD-2 in the limbus.

Animals↗

Antibody array-generated cytokine profiles of tears of patients with vernal keratoconjunctivitis or giant papillary conjunctivitis.

PURPOSE: To investigate differences in the cytokine and chemokine profiles of patients with vernal keratoconjunctivitis (VKC) or giant papillary conjunctivitis (GPC). METHODS: The study included six patients (six eyes) with VKC, five patients (five eyes) with GPC, and five healthy volunteers (five eyes) as controls. None of the patients had received any anti-allergic treatment prior to this study. One patient with VKC was given a tear examination to evaluate the effect of anti-inflammatory treatment with a steroid on the tear cytokine profile about the treatment. Tear samples were collected with the Schirmer I method, using filter paper. Tear samples were eluted and analyzed by an antibody array system for inflammation-related factors, including cytokines and chemokines. RESULTS: In the patients with VKC, four inflammation-related factors, eotaxin, interleukin (IL)-11, monocyte chemoattractant protein (MCP)-1, and macrophage-colony stimulating factor (M-CSF) increased to four times the values in the control group, and seven inflammation-related factors, eotaxin-2, IL-4, IL-6, interleukin-6 soluble receptor (IL-6sR), IL-7, macrophage inflammatory protein (MIP)-1delta, and tissue inhibitor of metalloproteinases (TIMP)-2, increased to eight times the control values. In the patients with GPC, three inflammation-related factors, IL-6, M-CSF, and monokine-induced gamma interferon (MIG), increased to four times those in the control group, and five inflammation-related factors, eotaxin-2, IL-6sR, IL-11, MIP-1delta, and TIMP-2, increased to eight times the control values. The increase in IL-6sR relative to the controls was statistically significant in both the VKC and GPC groups. The increase in eotaxin-2 was significant only in the VKC group, and that in TIMP-2 was significant only in the GPC group, compared with the controls. CONCLUSIONS: The present study demonstrated the presence of crucial cytokines, soluble cytokine receptors, and chemokines in tears of patients with VKC and GPC. In particular, IL-6sR increased significantly in both the VKC and GPC groups, whereas eotaxin-2 increased significantly only in the VKC group. Thus, IL-6sR may play an important pathophysiological role in giant papillary proliferation in VKC and GPC, and eotaxin-2 may play an important role in eosinophilic inflammation in VKC.

Adolescent↗

The pathogenesis of allergic conjunctivitis.

The clinical presentation of the various forms of allergic conjunctivitis varies greatly from mild symptoms to severe disease with vision-threatening complications. Although an IgE-mediated type-1 hypersensitivity reaction has been demonstrated or postulated in many types of allergic eye disease, the pathophysiology underlying the allergic conjunctivitides is not fully understood. The variety of currently available treatment options underscores the complexity of the chemical reactions associated with mast cell degranulation and mediator release causing the onset of allergic signs and symptoms. Many of these treatments are merely palliative and do not eliminate the complex immune response initiating the symptoms, so there is a recurrence of disease as soon as the therapy is discontinued. Models of allergic eye disease have significantly aided the discovery of new anti-allergic and anti-inflammatory compounds that can be used safely in the eye.

Acute Disease↗

Neurologic complications with elevated antibody titer after acute hemorrhagic conjunctivitis.

Nine patients with polyradiculomyeloneuropathy after acute hemorrhagic conjunctivitis (AHC) infection were studied serologically. All except one patient had neutralization titers larger than or equal to 1:16 against the prototype J670/71 strain of AHC virus in at least one of their serum samples. The development of a significant fourfold rise in antibody titer against AHC virus occurred in one of the patients who developed neurologic complications five days after the onset of AHC infection.

Acute Disease↗

Bulbar ligneous conjunctivitis after pterygium removal in an elderly man.

Ligneous conjunctivitis occurred unilaterally in a 74-year-old man after pterygium excision and only involved the bulbar conjunctiva. Histochemical studies confirmed the presence of mucopolysaccharides in the lesion sensitive to hyaluronidase. The patient was treated successfully with topical hyaluronidase and alpha-chymotrypsin, with no recurrence 20 months after cessation of therapy.

Adrenal Cortex Hormones↗

Marginal corneal ulcers with acute beta streptococcal conjunctivitis and chronic dacryocystitis.

A 73-year-old woman had right dacryocystitis, intense conjunctival hyperemia and chemosis, marginal corneal ulcers, and abscesses and conjunctival cultures that were positive for beta hemolytic streptococci. A distinct lucid interval separated the peripheral corneal ulcers and infiltrates from the corneoscleral limbus. Gram stain of corneal scrapings revealed polymorphonuclear leukocytes but no bacteria, and corneal cultures were negative for bacteria. The peripheral corneal ulcers and abscesses in our patient with the lacrimal conjunctivitis of Morax clinically resembled the catarrhal ulcers found with staphylococcal blepharitis. A hypersensitivity or toxic reaction to streptococci or their products may have played a role in the development of the marginal ulcers in this patient.

Aged↗

Treatment of ragweed allergic conjunctivitis with cromolyn sodium 4% ophthalmic solution.

We treated 31 patients with ragweed conjunctivitis in an eight-week, double-masked parallel-group study with cromolyn sodium 4% ophthalmic solution. Analysis of data showed preseason serum IgE antibody to ragweed level was a significant predictor of drug response. Of 16 patients with ragweed IgE values of less than 100 ng/ml, the nine treated with cromolyn had significantly fewer symptoms during the course of treatment than the seven in the placebo group. Of the 15 remaining patients, who had IgE levels of more than 100 ng/ml, the eight treated with cromolyn improved but the difference between their symptom scores and those of the seven patients treated with placebo was not statistically significant.

Adolescent↗

Interferon treatment of adenoviral conjunctivitis.

We conducted a randomized, double-masked, placebo-controlled study to evaluate the efficacy of topical interferon in the treatment of adenoviral conjunctivitis. The study was designed to determine the efficacy of plasmid-derived alpha-2 interferon treatment with regard to the duration of clinical disease, virus shedding, and the occurrence of bilateral infection and subepithelial infiltrates. Interferon therapy was not found to have a statistically significant effect with regard to these factors in the 14 patients who completed 14 days of treatment in the study with interferon or a placebo. Interferon therapy was, however, associated with a tendency toward asymptomatic infection in the second eye when compared to the controls.

Adenoviridae Infections↗

The clinical characteristics and course of adult gonococcal conjunctivitis.

We studied 21 cases of adult conjunctivitis caused by Neisseria gonorrhoeae, confirmed by either Gram's stain or culture, that were seen between 1972 and 1986. The patients, typically young men, had irritation or pain, a copious purulent discharge, and marked conjunctival inflammation. Keratitis, anterior chamber inflammation, periocular edema and tenderness, gaze restriction, and preauricular lymphadenopathy were common. All patients were hospitalized and treated with high doses of parenterally administered antibiotics. Two patients had severe ulcerative keratitis at initial examination, which ultimately resulted in light-perception visual acuity, despite antibiotic therapy and keratoplasty. In the remainder of the patients, corneal involvement was milder and transient, and treatment with parenteral penicillin and topical antibiotics was uniformly effective in reversing the course of the infection and preventing significant visual loss. Careful ophthalmologic and microbiologic monitoring is suggested to prevent possible complications caused by penicillin-resistant strains.

Adolescent↗

Neisseria meningitidis conjunctivitis in children.

We examined two children from the same family who had purulent conjunctivitis. Isolates of Neisseria species were obtained from eye cultures and Gram stain of conjunctival scrapings disclosed many gram-negative intracellular diplococci. Colony structure and growth characteristics of the organism with subsequent carbohydrate fermentation tests and serotyping were consistent with Neisseria meningitidis Group B. The patients had no neurologic signs or symptoms. Results of laboratory investigations and blood cultures were normal. Early diagnosis is mandatory and aggressive systemic therapy with appropriate antibiotics may prevent ocular, neurologic, or systemic complications.

Child, Preschool↗

The role of leukotriene D4 as a mediator of allergic conjunctivitis in the guinea-pig.

The role of leukotriene D4 (LTD4) as a mediator of conjunctival microvascular permeability changes associated with immediate hypersensitivity reactions in the guinea-pig conjunctiva has been investigated using two novel, selective LTD4 receptor antagonists, L-648,051 and L-649,923. Changes in microvascular permeability were measured through the accumulation of [99mTc]albumin. LTD4 administered intravenously produced dose-related increases in conjunctival microvascular permeability through a mechanism which does not involve the generation of prostaglandins as indicated by the failure of indomethacin to attenuate the response. The response to LTD4 was significantly blocked by the receptor antagonists, L-648,051 and L-649,923. Topical application of antigen (either single challenge or 2 challenges separated by 24 h) to the eyes of sensitized guinea-pigs caused significant increases in conjunctival microvascular permeability. Following a single challenge, the antigen response was largely blocked by mepyramine (H1 receptor antagonist), but was unaffected by L-648,051 and L-649,923. Following a second challenge (24 h later) a substantial portion of the response was inhibited by L-648,051 and L-649,923. Indomethacin failed to inhibit either challenge. These results suggest that LTD4 may have a role in chronic allergic conjunctivitis.

Animals↗

Electron microscopic observations concerning the in vivo uptake and release of the agent of guinea-pig inclusion conjunctivitis (Chlamydia psittaci) in guinea-pig exocervix.

This report details electron-microscopical observations concerning C. psittaci infection in vivo. The model employed was that of the guinea-pig infected at the exocervical region with the agent of guinea-pig inclusion conjunctivitis (GPIC). Our observations indicate that chlamydial particles gain access to their target cells by the mechanism of endocytosis. Single GPIC elementary bodies were seen to be positioned within individual endosomes. The observations reported here provide evidence that chlamydial particles that had undergone their developmental cycle within the exocervical epithelial cells may leave the epithelium in 2 ways; within entire infected cells that had been shed into the lumen of the cervix and by means of the liberation of chlamydial particles from disrupted cells. The mechanism of cell disruption and shedding is thought to involve the large number of PMNs observed to be present within the enlarged intercellular spaces of the infected epithelium.

Animals↗

Radiculomyelitis complicating acute haemorrhagic conjunctivitis. A clinical study.

Fourteen patients with radiculomyelitis following acute haemorrhagic conjunctivitis (AHC) were seen in Bangkok during October to December 1974. Most patients developed weakness of extremities 2 weeks after AHC. Prodromal symptoms consisted of fever and malaise for a few days, followed by the acute onset of root pain in the legs and flaccid paralysis. Knee and ankle reflexes were absent or diminished. Cerebrospinal fluid examination revealed lymphocytosis and an increase in protein. Electromyographic findings were consistent with anterior horn cell or motor root lesions. Ten of the 12 cases in which virological studies were performed showed definite serological evidence of AHC virus infection. Six patients received corticosteroid treatment but apart from relief of pain no significant improvement was seen. Motor weakness in 10 patients was less at the end of 2 months, but in 4 it remained unchanged. The occurrence of disabling neurological sequelae calls for effective public health control of AHC outbreak.

Acute Disease↗

Neurological complications of acute haemorrhagic conjunctivitis.

Forty four cases of the neurological complications of acute haemorrhagic conjunctivitis (AHC) seen in India during 1981 epidemic are reported. The disease predominantly affected adult males. The preceding attack of AHC, a latent period, prodromal symptoms of fever, myalgia and root pains followed by acute onset of lower motor neurone paralysis of limbs and/or cranial nerves formed the classical picture of neurological involvement. The recovery was poor and nearly half of the patients remained severely handicapped. Electrophysiological studies showed early appearance of widespread fibrillations and fasciculations, large polyphasic potentials of increased amplitude and reduced interference pattern. Nerve conduction studies were normal in most of the cases. Cerebrospinal fluid (CSF) examination revealed lymphocytic pleocytosis and rise in protein content. Significant antibody titres against enterovirus type 70 (EV 70) were demonstrated in the serum and the CSF. HLA studies showed low occurrence of A2 and B15 HLA antigens. Muscle biopsies revealed neurogenic atrophy and sural nerve biopsies were histologically unremarkable. The similarities of this disease with poliomyelitis and its pathogenesis are discussed.

Adolescent↗

Isolation of enterovirus 70 (EV70) from patients with acute haemorrhagic conjunctivitis in two areas of Saudi Arabia.

This is the first epidemic of acute haemorrhagic conjunctivitis (AHC) reported from Saudi Arabia in which enterovirus 70 (EV70) was implicated as aetiological agent. EV70 was isolated from 5 of 29 conjunctival scrapings from patients with AHC. Two human diploid cell lines, human skin fibroblast (HSF) and human embryonic lung fibroblast (MRC-5), were quite sensitive for the isolation of this virus. The relatively high isolation rate could also be attributed to the timing of collection of specimens and perhaps to the fact that conjunctival scrapings contained more virus particles than did eye swabs.

Adolescent↗