Eyedrop Inoculation Causes Sublethal Leptospirosis in Mice.

Leptospirosis is potentially a fatal zoonosis acquired by contact of skin and mucosal surfaces with soil and water contaminated with infected urine. We analyzed the outcome of infection of C3H/HeJ mice with Leptospira interrogans serovar Copenhageni using an enzootic mode of transmission, the conjunctival route. Infection led to weight loss and L. interrogans dissemination from blood to urine, and spirochetes were detected in blood and urine simultaneously. The infectious dose that led to consistent dissemination to kidney after conjunctival infection was ∼108 leptospires. Interestingly, a lower number of spirochetes appeared to colonize the kidney, given that we quantified ∼105 and ∼10 leptospires per µl of urine and per µg of kidney, respectively. Leptospira-specific IgM and IgG were detected at 15 days postinfection, and isotyping of the Ig subclass showed that the total IgG response switched from an IgG1 response to an IgG3 response after infection with L. interrogans Histological periodic acid-Schiff D staining of infected kidney showed interstitial nephritis, mononuclear cell infiltrates, and reduced size of glomeruli. Quantification of proinflammatory immunomediators in kidney showed that keratinocyte-derived chemokine, macrophage inflammatory protein 2, RANTES, tumor necrosis factor alpha, gamma interferon, and interleukin-10 were upregulated in infected mice. We show that the kinetics of disease progression after infection via the ocular conjunctiva is delayed compared with infection via the standard intraperitoneal route. Differences may be related to the number of L. interrogans spirochetes that succeed in overcoming the natural defenses of the ocular conjunctiva and transit through tissue.

Lacrimal gland ductulitis caused by probable Actinomyces infection.

OBJECTIVE: To describe the clinical characteristics and management of a group of patients who had chronic mucopurulent conjunctivitis that was probably due to Actinomyces infection of the lacrimal gland ductules. DESIGN: A retrospective, interventional case series. PARTICIPANTS: Seven patients (2 male; 29%) between 34 and 52 years of age (mean, 48.7 years; median, 49 years) who presented to the lacrimal clinic. INTERVENTION: Surgical excision of the infective focus (6 cases) or fenestration and expression of infective debris (1 case) from the affected lacrimal gland ductule--typically the most inferolateral of the ductules. MAIN OUTCOME MEASURES: The clinical features of this previously unrecognized cause of chronic conjunctivitis and its response to treatment. RESULTS: All cases settled rapidly after surgery. There was often a major delay in diagnosis, with the patients having symptoms for between 2 and 42 months before referral (mean, 13.3 months; median, 9 months); 5 patients received prolonged or ineffectual topical medical therapy before referral. CONCLUSIONS: Infective lacrimal gland ductulitis, commonly from Actinomyces infection, should be considered in patients with unexplained chronic mucopurulent conjunctivitis; the condition settles rapidly with surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Assessment of Streptococcus pneumoniae capsule in conjunctivitis and keratitis in vivo neuraminidase activity increases in nonencapsulated pneumococci following conjunctival infection.

PURPOSE: The pneumococcal capsule is required for pathogenesis in systemic infections, yet reports show most conjunctivitis outbreaks are caused by nonencapsulated pneumococci, while keratitis infections are caused by encapsulated strains. This study aims to determine the effect of capsule in pneumococcal keratitis and conjunctivitis in rabbit models of infection. METHODS: A capsule-deficient isogenic mutant was created using homologous transformation. Parent and mutant strains were injected within the upper bulbar conjunctiva (conjunctivitis) or into the corneal stroma (keratitis) of New Zealand white rabbits. Clinical examinations were performed 24 and 48 hr post-infection at which time corneas or conjunctivae were removed, homogenized, and plated to determine the recovered bacterial load. Whole eyes were removed for histological examination. The neuraminidase activity was determined following in vitro and in vivo growth. RESULTS: There were no significant differences in clinical scores between the eyes infected with the parent or mutant for either infection, nor was there a difference in the amount of bacteria recovered from the cornea. In the conjunctivae, however, the mutant strain was cleared by the host faster than the parent strain. Histological examination showed slightly more infiltrating polymorphonuclear leukocytes (PMN) and macrophages in the conjunctivae infected with the parent strain. The neuraminidase activity of both strains was not significantly different when the strains were grown in vitro. However, the neuraminidase activity of the parent was significantly less than that of the mutant at 3 and 12 hr post conjunctival infection. CONCLUSIONS: Although more outbreaks of pneumococcal conjunctivitis are tied to nonencapsulated S. pneumoniae strains, this study showed that an encapsulated strain was capable of establishing conjunctivitis in a rabbit injection model and survive attack by the host immune system longer than its nonencapsulated isogenic mutant. Nonetheless, the nonencapsulated pneumococci had an increased neuraminidase activity level in vivo when compared to the parent strain.

Oculoglandular syndrome caused by Yersinia pseudotuberculosis in a dairy goat.

An outbreak of ocular disease in a herd of housed dairy goats was characterized by severe granulomatous conjunctivitis and ipsilateral parotid and submandibular lymphadenopathy. In one case submitted for post-mortem examination, Yersinia pseudotuberculosis was isolated from both the conjunctiva and submandibular lymph node. Histopathological examination identified severe chronic active suppurative and lymphoplasmacytic conjunctivitis and suppurative and necrotizing lymphadenitis associated with bacteria of yersinial morphology. Similar pathological changes occur in Parinaud's oculoglandular syndrome in man due to infection with Y. pseudotuberculosis.

Enhanced release of IL-6 and IL-8 into tears in various anterior segment eye diseases.

OBJECTIVE: To determine the levels of interleukin 6 (IL-6) and interleukin 8 (IL-8/CXCL-8) in tears collected from the eyes of normal individuals and of patients with different irritative eye diseases, in order to acquire information on the immunological changes occurring during the early postoperative period following various forms of eye surgery, including penetrating keratoplasty (PKP). METHODS: IL-6 and IL-8 levels were measured with the aid of human ultrasensitive ELISA kits in the non-stimulated tears of patients in the early postoperative period following PKP or cataract operation, and of patients with acute bacterial conjunctivitis or with a corneal foreign body. The IL-6 and IL-8 concentrations, the total amounts released in a given time and the rates of their release were calculated. RESULTS: A significant increase in IL-6 release was observed in all patient groups compared with the normal controls (p < or = 0.003). The IL-8 release levels were significantly higher in the tears of all patient groups (p < or = 0.03), except for the cataract operation group, where the IL-8 release was not significantly higher (p = 0.053) than in the control samples. No significant differences in IL-6 or IL-8 release were observed when the various patient groups were compared with each other. CONCLUSION: The release of IL-6 and IL-8 into the tears is enhanced in various anterior segment eye diseases, and this may be used as an indicator of various inflammatory reactions in the early postoperative period.

Infectious keratitis after photorefractive keratectomy in a comanaged setting.

A 48-year-old man had simultaneous bilateral photorefractive keratectomy (PRK). The surgeon who performed the PRK did not see the patient in follow-up, and there was confusion regarding the comanaging doctor. Therefore, the patient was not examined immediately postoperatively. Several days later, he was hospitalized for an unrelated, painful orthopedic problem and heavily sedated. Seven days after the PRK, an ophthalmologist was consulted for ocular irritation and discharge. Examination showed bilateral, purulent conjunctivitis and severe infectious keratitis in the left eye. The patient was treated with periocular and topical antibiotics. Corneal cultures yielded Staphylococcus aureus. The keratitis resolved slowly, leaving the patient with hand motion visual acuity. A corneal transplant and cataract extraction was performed 15 months later, resulting in a best corrected visual acuity of 20/400 because of glaucomatous optic nerve damage. Severe infectious keratitis may occur after PRK. Poor communication between the surgeon, comanaging doctor, and patient may result in treatment delay.

Comparison of cyclosporin A and dexamethasone in the treatment of canine nictitans plasmacytic conjunctivitis.

Thirteen dogs with nictitans plasmocytic conjunctivitis were treated with 2.0 per cent cyclosporin drops in the right eye and with 0.1 per cent dexamethasone ointment in the left eye. The response to both therapies was monitored for six weeks, repeat biopsy specimens were taken, and the time for the clinical signs to recur recorded. Conjunctival cultures were taken before and after both therapies. There were no significant differences between the treatments in the remission of clinical signs, the reduction of inflammatory infiltrate in the biopsy specimens, or the time to recurrence of the condition or its subsequent severity. However, the eyes treated with 0.1 per cent dexamethasone tended to recover more rapidly than the eyes treated with 2.0 per cent cyclosporin, and the eyes treated with 2.0 per cent cyclosporin tended to be protected from a recurrence for longer than the eyes treated with 0.1 per cent dexamethasone.

Nosocomial Klebsiella pneumoniae conjunctivitis resulting in infectious keratitis and bilateral corneal perforation.

PURPOSE: Klebsiella pneumoniae is a known cause of metastatic endophthalmitis. However, the organism has never been described to cause severe infectious keratoconjunctivitis. We report a fulminant case of nosocomial K. pneumoniae conjunctivitis complicated by infectious keratitis and corneal perforation in both eyes. METHODS: An 83-year-old previously healthy Chinese woman, blind in the right eye from rubeotic glaucoma and with bilateral dense cataracts, was admitted for observation after a head injury. While in hospital, she developed purulent bilateral conjunctivitis. Repeated cultures grew K. pneumoniae. This rapidly progressed to severe infectious keratitis and corneal perforation in both eyes, despite intensive antibiotics to which the organism was susceptible. The patient was otherwise well, and investigations did not reveal any source of endogenous sepsis. RESULTS: The patient lost complete vision in both eyes. The left eye turned phthisical, and the right eye was eviscerated for uncontrolled endophthalmitis. CONCLUSION: Although not previously reported, K. pneumoniae can cause devastating keratoconjunctivitis resulting in corneal melt, perforation, and uncontrolled endophthalmitis.

Characterization of the systemic disease and ocular signs induced by experimental infection with Chlamydia psittaci in cats.

In addition to the commonly reported ocular signs, Chlamydia psittaci infection of kittens resulted in fever, lethargy, lameness and reduction in weight gain following ocular instillation of virulent organisms. The appearance of these systemic signs was late with respect to the appearance of ocular symptoms and occurred simultaneously with increasing levels of chlamydia-specific IgG. Measurement of acute phase reactants and IL-6 in plasma indicated that both became elevated concurrent with or slightly after the appearance of fever and remained elevated after the fever began to resolve. Preliminary data also indicated that infectious C. psittaci was present in the blood stream during this time period. The results of ocular instillation of three different levels of C. psittaci (10(3.8), 10(2.8) and 10(1.5) TCID50) indicated that the frequency of infection and the severity of ocular signs were diminished in the group receiving the lowest dose. However, the magnitude of systemic disease was similar in all animals which exhibited clinical signs, irrespective of the dose administered. The immune response to infection included elementary body (EB)-specific lymphocyte proliferation as well as the development of EB-specific IgG and IgM antibodies. The predominant antibody response was to a 45 kDa protein, the major outer membrane protein (MOMP), lipopolysaccharide (LPS), a 58 kDa doublet and 32 and 16-19 kDa proteins.

Conjunctival scrapings and impression cytology in chronic conjunctivitis. Correlation with microbiology.

To assess the utility of exfoliative cytology in the diagnosis of chronic conjunctivitis, we compared its findings with microbiological examination and established the correlation between cytology and microbiology in 32 patients with conjunctivitis lasting four weeks or more, with a nonspecific clinical picture. The material for cytology was collected by scraping and by imprint of the ocular surface on Millipore filter paper. The specimens were stained with Giemsa. Material for bacterial culture and fluorescent antibody test for viruses and Chlamydia were obtained at the same time. In 12 patients neutrophils predominated in cytology, in six eosinophils were found and in four there were more lymphocytes. One patient had a basophilic intracytoplasmic inclusion specific for Chlamydia infection. In eight patients coagulase-negative Staphylococcus species and in one Staphylococcus aureus were isolated, in two the fluorescent antibody test for Chlamydia was positive and in three for viruses. In all patients with a positive bacterial culture, a predominance of neutrophils was observed. All patients with a positive test for viruses had lymphocytosis in conjunctival scrapings. In two patients microbiology detected Chlamydia, but characteristic intracytoplasmic inclusions were observed only in one. Scrapings gave more specific results, that correlated well with microbiology in bacterial and viral infection, whereas the results of impression cytology showed minor metaplastic changes of epithelial cells that were nonspecific for the type of inflammation. Cytology remains a useful non-invasive tool and is an adjunct to clinical and microbiological examination. It proved especially helpful in allergic conjunctivitis.

Conjunctival mycobacteriosis in two emus (Dromaius novaehollandiae).

Avian tuberculosis was diagnosed in two young adult female commercial emus (Dromaius novaehollandiae) with granulomatous conjunctivitis. Histologically, the granulomas appeared typical of avian tuberculosis. Caseonecrotic cores were surrounded by a broad ring of palisading epithelioid macrophages and multinucleate giant cells with a moderate admixture of heterophils, lymphocytes, and plasma cells. One conjunctival granuloma had multifocal mineralization. At necropsy, granulomas were also found in visceral organs of both birds. Acid-fast bacilli were demonstrated in all lesions using Ziehl-Neelsen or Fite's stains. Culture confirmed the bacilli to be Mycobacterium avium (complex).

[Perinaud's oculoglandular syndrome as a manifestation of cat-scratch disease]. / Parinauds okuloglandulaere syndrom som en manifestation af kattekradssygdommen.

The first Danish case of Parinaud's oculoglandular syndrome, a manifestation of cat-scratch disease, is reported in a 35-year-old man presenting with an enlarged preauricular lymph node and an ipsilateral conjunctival granuloma. Surgical removal of the granulomatous lesion was followed by rapid healing. The diagnosis was verified by demonstrating a high antibody tire against Rochalimaea (Bartonella) henselae. On subsequent questioning the man gave a history of acquiring a kitten six weeks before his illness. The importance of eye examination in patients presenting with preauricular lymphadenopathy is emphasized.

Conjunctival biopsy in patients with Kawasaki disease.

Kawasaki disease (KD) is an acute vasculitis of infants and young children that is associated with bilateral nonexudative conjunctivitis during the acute illness. Epidemiologic evidence has suggested an infectious cause but the etiology of KD remains unknown. We examined conjunctival biopsy specimens from seven patients with typical KD to characterize the pathologic changes during the acute disease. Light microscopic examination revealed nonspecific, mild inflammatory changes that included vascular dilatation, infiltration with scattered lymphocytes, increased numbers of plasma cells in the conjunctival stroma, and increased prominence of goblet cells in the epithelium. No pathogens were identified by special stains for bacteria and rickettsiae, nor were viral particles seen by electron microscopy. We conclude that the conjunctivitis of acute KD is characterized by vascular dilatation with a mild mononuclear cell response with no pathognomonic features. The conjunctiva can be readily sampled in these patients and biopsy may prove useful in selected patients to exclude other clinical entities in the differential diagnosis.

[Keratomalacia in rheumatoid arthritis: immunohistologic and enzyme histochemical studies]. / Keratomalazie bei rheumatoider Arthritis: immunhistologische und enzymhistochemische Untersuchungen.

Corneal and conjunctival biopsies of 13 patients with rheumatoid arthritis and corneal ulceration (RA-keratomalacia) have been characterized by immunohistological and histochemical analysis. Biopsies from 13 patients with bacterial conjunctivitis, 7 patients with allergic conjunctivitis, 15 patients with senile cataract and 15 patients with keratokonus served as controls. The phenotypic composition of the conjunctival inflammatory infiltration of rheumatoid corneal ulceration was not significantly different from the other inflammatory eye diseases studied. However, conjunctival epithelial cells of all RA-patients showed strong de novo expression of HLA-DR- and DP-antigens. HLA-DQ-antigens were only weakly expressed in a minority of patients. In bacterial conjunctivitis a less intense HLA-class-II-expression was found to be restricted to HLA-DR-antigens. Furthermore, in RA patients stromal fibroblasts of the cornea expressed lysosomal elastase. Both observations could be explained by paracrine action of interleukins produced by infiltrating T-lymphocytes and macrophages. Thus, it might be tempting to speculate that immunologically induced, elastase mediated autodegradation of corneal stroma may be an important factor in the pathogenesis of rheumatoid corneal ulceration.