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The effect of topical pimecrolimus on keratoconjunctivitis sicca and chronic superficial keratitis in dogs: results from an exploratory study.

OBJECTIVE: Pimecrolimus is an ascomycin derivative that interferes selectively with the activation of T cells and mast cells and inhibits the production of inflammatory cytokines. This study evaluated the efficacy of an experimental ophthalmic formulation of pimecrolimus in treating keratoconjunctivitis sicca (KCS) and chronic superficial keratitis (CSK) in dogs. ANIMALS AND PROCEDURES: Eight dogs with KCS and six with CSK were included. The dogs were of various breeds, suffered from chronic conditions, and had been pretreated unsuccessfully. The affected eyes were treated with 1 drop of an experimental, corn oil-based pimecrolimus 1% formulation three times a day. Parameters evaluated included Schirmer tear test (STT), ocular discharge, conjunctival inflammation, corneal inflammatory cell infiltrate and scarring, and comfort level. RESULTS: The effect of pimecrolimus 1% was pronounced (increase in STT values to higher than 4 mm/min, no signs of inflammation) or moderate (increase in STT values of 3-4 mm/min, mild signs of corneal/conjunctival inflammation) in a total of 6/8 animals with KCS. In 4/6 animals with CSK, the effect was either pronounced (total regression of fibrovascular infiltration into the cornea, no corneal scarring) or moderate (distinct regression of pannus, mild corneal scarring). The response to treatment was unsatisfactory in four of 14 animals. CONCLUSION: Results of this exploratory study suggest that topical 1% pimecrolimus may be a new effective treatment for keratoconjunctivitis sicca and chronic superficial keratitis in dogs.

Animals↗

Test and symptoms in keratoconjunctivitis sicca and their correlation.

Results of dry eye tests and ocular symptoms were compared and correlated in patients with primary Sjögren's syndrome (1 degree SS), in patients with connective tissue disease differing from 1 degree SS, and in normal controls. Patients with 1 degree SS had many and pronounced ocular complaints, however, non-diagnostic for the disease. Break-up time and Schirmer-1 test results below 10 mm/5 min both had high sensitivity but low specificity, whereas the reverse was true for Rose-Bengal score and Schirmer-1 test below 5 mm/5 min. Presence of snake-like chromatin in conjunctival imprints and the lactotest on tear fluid did not qualify as alternative tests since they had very low specificity and were less sensitive than the Schirmer-1 test and break-up time. Cornea sensitivity was not found to be an appropriate test at all. In 21% of eyes the presence of keratoconjunctivitis sicca changed from one consultation to the next in patients with 1 degree SS. Examination for keratoconjunctivitis sicca should therefore be repeated in test negative cases where symptoms indicate 1 degree SS.

Adult↗

Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in the cavalier King Charles spaniel.

OBJECTIVES: To record a previously unreported congenital and hereditary condition affecting the eyes and skin in the cavalier King Charles spaniel. METHODS: Nineteen cases (13 litters) were investigated, with particular reference to eye and skin clinical signs. In addition, five generation pedigrees were obtained and studied from all cases with the exception of one. RESULTS: The eye signs were due to keratoconjunctivitis sicca, a common ocular disease in the dog, but rarely of congenital origin. The skin signs were of an ichthyosiform dermatosis; ichthyosis being a rare skin disease in the dog. In human beings, ichthyosis is a similar disease, mainly inherited and with a neonatal onset, and sometimes accompanied by other developmental defects. In the cavalier King Charles spaniel, the coat abnormality was noted at birth by the breeders as a 'curly coat', with deterioration of the skin signs as the animal became adult. CLINICAL SIGNIFICANCE: These two conditions occurring together in this breed is well recognised by some breeders but rarely by the veterinary profession. Successful treatment is not possible, although some improvement, particularly of the keratoconjunctivitis sicca, can be obtained. The probable hereditary nature of the condition is an important factor for control.

Animals↗

Infectious bovine keratoconjunctivitis vaccine development.

Infectious bovine keratoconjunctivitis is a common and highly contagious ocular disease affecting cattle worldwide. The tremendous economic losses attributable to this disease warrant continued investigation into methods of prevention. Multiple virulence factors have been linked to the primary aetiologic agent, Moraxella bovis. Efforts to develop an efficacious vaccine have primarily focused upon the use of surface pili or cytolysin to stimulate host immunity; however, M. bovis possesses other virulence determinants that include proteases, fibrinolysins, phospholipases and other cell surface components such as outer membrane proteins. These potentially conserved antigens provide additional possibilities for vaccine development. Examination of appropriate antigen presentation is necessary to attain an adequate immune response. Further, the potential for antigenic diversity as well as epitope conversion requires continuous epidemiological surveillance of isolates recovered from outbreaks. Current work targeting conserved immunogens provides hope for efficacious vaccines that when used in tandem with proper management may control, if not prevent, infectious bovine keratoconjunctivitis.

Animals↗

Treatment of keratoconjunctivitis sicca with liquid paraffin or polyvinyl alcohol in double-blind trial.

Twenty-two eyes affected with keratoconjunctivitis sicca have been subjected to double trials using the double-blind randomized cross-over technique. Polyvinyl alcohol in a 5% concentration improved the condition whereas liquid paraffin aggravated it, as estimated subjectively, and by the measurement of the break up time of the corneal film, and, finally, by the scoring of rose bengal vital staining of exposed cornea and conjunctiva. The conclusion is drawn that oil is contraindicated in keratoconjunctivitis sicca, and that rose bengal scoring (modified Bijsterveld method) is a valuable aid in control of the sicca syndrome.

Adult↗

'Snake-like' appearance of nuclear chromatin in conjunctival epithelial cells from patients with keratoconjunctivitis sicca.

Millipore filter imprints of conjunctiva in patients with conjunctival symptoms revealed a 'snake-like' appearance of the chromatin in nuclei of epithelial cells. A total of 40 patients were investigated. Abnormal cells were found in 8/16 patients with long-term keratoconjunctivitis sicca and in 6/24 patients suspected for Sjøgrens syndrome. The abnormal cells were typically arranged in clusters among morphologically normal epithelial cells. The finding was significantly correlated to the severity of the disease in patients with keratoconjunctivitis sicca. In all patients the abnormal cells could only be detected in millipore imprints of the upper bulbar conjunctiva and not in scrapings from the same area. The significance of the findings are discussed.

Chromatin↗

A comparative clinical study of tear substitutes in normal subjects and in patients with keratoconjunctivitis sicca.

The effect upon the tear film of a new tear substitute, Dacriosol, was compared to a non-viscous solution, saline, an to a highly viscous solution, Isopto Plain, in 15 normal healthy subjects and in 15 patients with mild to moderate keratoconjunctivitis sicca. No differences between the test solutions could be measured 3 h after last medication regarding: Schirmer's test, break-up time, rose bengal staining, corneal sensitivity and tear content of lysozyme. The test persons could not discriminate subjectively between the effect of the test solutions. The investigation parameters show an equal effect of Dacriosol, Isopto Plain and saline both in normal healthy subjects and in patients with keratoconjunctivitis sicca.

Adult↗

The central corneal thickness in keratoconjunctivitis sicca.

The central corneal thickness of 17 patients with keratoconjunctivitis sicca was compared with the thickness recorded in a control group of 105 subjects with healthy eyes. A moderate, but highly statistically significant central corneal thinning was found in the keratoconjunctivitis sicca group. The possible etiology and clinical importance of this finding is briefly discussed.

Adolescent↗

Herpetic keratoconjunctivitis: therapy with synthetic double-stranded RNA.

A study was undertaken in rabbits to determine how late in the course of keratoconjunctivitis caused by herpes simplex recovery could be effected by an inducer of interferon. Interferon was induced by means of synthetic double-stranded RNA copolymer formed with polynosinic acid: polycytidilic acid RNA. Therapy promotes recovery from severe and fully established keratoconjunctivitis for which treatment was begun as late as 3 days after virus inoculation. No drug toxicity was observed in the therapeutic dose range. These findings further support the proposed role of the interferon mechanism in the natural recovery of already established viral infection. They also suggest the usefulness of interferon inducers in viral infections of man.

Animals↗

Efficacy of hospital germicides against adenovirus 8, a common cause of epidemic keratoconjunctivitis in health care facilities.

The inactivation of virus-contaminated nonporous inanimate surfaces was investigated using adenovirus type 8, a common cause of epidemic keratoconjunctivitis. A 10-microl inoculum of adenovirus was placed onto each stainless steel disk (1-cm diameter), and the inoculum was allowed to air dry for 40 min. Twenty-one different germicides (including disinfectants and antiseptics) were selected for this study based on their current uses in health care. After a 1- or 5-minute exposure to 50 microl of the germicide, the virus-germicide test mixture was neutralized and assayed for infectivity. Using an efficacy criterion of a 3-log10 reduction in the titer of virus infectivity and regardless of the virus suspending medium (i.e., hard water, sterile water, and hard water with 5% fetal calf serum), only five disinfectants proved to be effective against the test virus at 1 min: 0.55% ortho-phthalaldehyde, 2.4% glutaraldehyde, 2.65% glutaraldehyde, approximately 6,000 ppm chlorine, and approximately 1,900 ppm chlorine. Four other disinfectants showed effectiveness under four of the five testing conditions: 70% ethanol, 65% ethanol with 0.63% quaternary ammonium compound, 79.6% ethanol with 0.1% quaternary ammonium compound, and 0.2% peracetic acid. Of the germicides suitable for use as an antiseptic, 70% ethanol achieved a 3-log10 reduction under four of the five test conditions. These results emphasize the need for proper selection of germicides for use in disinfecting noncritical surfaces and semicritical medical devices, such as applanation tonometers, in order to prevent outbreaks of epidemic keratoconjunctivitis.

Adenoviridae↗

Epidemic caprine keratoconjunctivitis: recovery of Mycoplasma conjunctivae and its possible role in pathogenesis.

Clinical, microbiological, serological, histological, and therapeutic aspects of two separate outbreaks of caprine keratoconjunctivitis are described. The disease was characterized by a high rate of contagion, rapid onset, intense lacrimation, conjunctival hyperemia, and corneal opacity with neovascularization. In addition, many of the animals developed respiratory illness during the second epidemic. The only organism consistentlyisolated was Mycoplasma conjunctivae. A total of 23 strains were isolated from 18 inflamed conjunctivae, one normal conjunctiva, and the nasal secretions of four goats with concomitant respiratory illness. The convalescent sera of goats in the first outbreak had neutralizing antibody titers to M. conjunctivae that ranged from 1:32 to 1:256. In the milder second outbreak the antibody titers ranged from 1:4 to 1:32 in animals with only ocular disease and from 1:4 to 1:64 in animals with only respiratory disease. Whereas little change was noted in antibody titers of goats with only localized eye disease, 43% of the goats with respiratory disease showed significant fourfold rises. The histological picture was consistent with acute corneal infection. Animals requiring antibiotic treatment appeared to respond favorably to a combination of oxytetracycline and polymyxin B, but not to penicillin. These findings suggest that M. conjunctivae is one cause of epidemic caprine keratoconjunctivitis.

Animals↗

Epidemic caprine keratoconjunctivitis: experimentally induced disease with a pure culture of Mycoplasma conjunctivae.

The induction of caprine keratoconjunctivitis by the subconjunctival inoculation of a cloned culture of Mycoplasma conjunctivae is described. The clinical course of the experimental disease was similar to that noted in naturally occurring outbreaks of "pink-eye" among goats, and biopsies of inflamed conjunctivae showed similar histological response. M. conjunctivae was consistently recovered from the inflamed conjunctival tissues of inoculated animals that developed ocular disease, thus fulfilling Koch's postulates and establishing this organism as an etiological agent of caprine keratoconjunctivitis. Immunological studies suggested that cellular immune mechanisms may play a role in protecting animals from disease produced by this mycoplasma.

Animals↗

Protection against keratoconjunctivitis shigellosa induced by immunization with outer membrane proteins of Shigella spp.

Active immunization of guinea pigs and rabbits with outer membrane proteins (OMP) isolated from Shigella flexneri 3a and Shigella sonnei phase I protected the animals against keratoconjunctivitis shigellosa induced with the homologous or heterologous strain. Protection was also achieved in rabbits after passive immunization with anti-OMP immune serum. Active immunization with lipopolysaccharide of S. flexneri 3a did not protect rabbits against keratoconjunctivitis shigellosa.

Animals↗

HeLa cell invasiveness and O antigen of Shigella flexneri as separate and prerequisite attributes of virulence to evoke keratoconjunctivitis in guinea pigs.

Many rough mutants selected from isogenic smooth virulent and avirulent strains of Shigella flexneri were examined for virulence, using tissue culture infection and Sereny tests. Many of the rough mutants isolated from a virulent smooth strain were capable of penetrating tissue culture cells but incapable of producing a positive Sereny test. In contrast, we could not obtain from smooth avirulent strains any rough mutants capable of penetrating HeLa cells. Chemical analysis of lipopolysaccharide of some representative rough strains showed several patterns of sugar composition with a range of from Ra to Re chemotypes. There was no correlation between HeLa cell invasiveness and chemotypes of lipopolysaccharides, thus indicating little significance of oligosaccharides of the rough core as well as O antigens in the ability of S. flexneri to penetrate HeLa cells. When these invasive rough strains were given O antigen genes from a smooth avirulent Shigella Hfr strain, most of the transconjugants that expressed O antigens regained the ability to evoke keratoconjunctivitis in guinea pigs. We also examined the chromosomal loci of HeLa cell invasion by transferring carbohydrate fermentation genes of Escherichia coli K-12 Hfr and found two chromosomal loci, the rha and lac-gal regions, which control the ability to penetrate HeLa cells. These results suggested that O antigens and ability to penetrate tissue culture cells are independent and prerequisite attributes of virulence in Shigella flexneri to evoke keratoconjunctivitis in guinea pigs.

Animals↗

Isolation and characterization of Mycoplasma conjunctivae sp. n. from sheep and goats with keratoconjunctivitis.

Fourteen conjunctival strains of mycoplasma were isolated from infected sheep and goats in two separate naturally occurring outbreaks of keratoconjunctivitis (pink-eye). The biological and serological properties and cell protein patterns of these strains are presented in this report. These strains were related to each other and were unrelated to 40 recognized Mycoplasma and Acholeplasma species and serotypes. We are proposing that this group of mycoplasmas be named M. conjunctivae. The role of M. conjunctivae in the etiology of keratoconjunctivitis in sheep and goats remains to be determined.

Animals↗

Adenovirus type 21 keratoconjunctivitis.

A case of keratoconjunctivitis caused by adenovirus type 21 in London has been described. A 59-year-old woman attented hospital in August 1974 complaining of a 3-week history of redness, grittiness, watery discharge, and photophobia in her left eye and a slight upper respiratory infection. Clinical examination showed a moderate follicular conjuctivitis mainly in the lower and upper fornices, which lasted for 6 weeks. In the cornea a moderate amount of epithelial and subepithelial punctate keratitis was observed. The subepithelial opacities were coarse, discrete, and round and lasted for 4 months. The course of follicular conjunctivitis and the subepithelial punctate keratitis in this patient was similar to epidemic keratoconjunctivitis caused by adenovirus 8. A conjunctival swabbing collected from this patient was positive for adenovirus serotype 21.

Adenoviridae Infections↗

Acute follicular conjunctivitis and keratoconjunctivitis due to herpes simplex virus in London.

During the 18 months January 1975 to June 1976, 25 cases of acute herpetic follicular conjunctivitis and keratoconjunctivitis resembling adenovirus ocular infection presented in the External Eye Disease Clinic, Moorfields Eye Hospital, City Road, London. Herpes simplex virus was isolated in HEp2 cells in 22 patients, and the remaining 3 patients were identified by a minimum 4-fold rise in the level of antiherpes simplex virus antibody in their blood. No adenovirus was isolated from these patients, but complement fixation test for adenovirus was positive in 1 patient with cultural test positive for herpes simplex virus. Most patients were between 20 and 35 years old and the ratio of males to females was 12 to 13. At the initial visit the clinical features of disease were moderate to severe conjunctival papillary and follicular reasons with epithelial and subepithelial punctate keratitis but little systemic disease. In the absence of typical herpetic lesions of face, lids, or cornea the disease resembled adenovirus types 8 or 19 keratoconjunctivitis. Of these 25 patients 5 subsequently developed typical herpetic lesions of lids or cornea. In the remaining 20 cases the correct diagnosis could be made only by cultural or serological tests. Virological diagnosis provides a rational basis for antiherpetic chemotherapy, which appears to shorten the course of infection.

Adolescent↗

Destructive epidemic Neisseria gonorrheae keratoconjunctivitis in African adults.

An epidemic of Neisseria gonorrheae keratoconjunctivitis in African adults occurred in Malawi in 1983. Sixteen patients, seven females and nine males, aged 18 to 60 years, were admitted to the inpatient ocular services at Queen Elizabeth Central Hospital in Blantyre from 1 February to 28 May 1983, all with severe bilateral purulent keratoconjunctivitis and concomitant venereal infection secondary to N. gonorrheae. Corneal melting, corneal perforation with iris prolapse, and endophthalmitis occurred in 10 eyes, of which five required enucleation. Thirteen additional eyes sustained severe visual loss secondary to corneal ulceration, leucomata, and healed corneal perforation. The route of transmission and factors of epidemicity are speculative. Because of worldwide epidemic venereal infection ophthalmologists and epidemiologists should be alert to probable sporadic N. gonorrheae epidemics in adults. Such outbreaks could occur elsewhere, especially in the developing world, and ocular gonococcal infection might become a significant cause of irreversible blindness.

Adolescent↗