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Inclusion keratoconjunctivitis ('pink eye') in sheep. A proposal for a new name for chlamydial keratoconjunctivitis in sheep and comment on recent clinical trials.

The cytoplasmatic inclusion bodies, which, in 1931, Coles discovered in the corneal cells of sheep suffering from contagious keratoconjunctivitis are now considered to be the reticulate bodies of a chlamydia, Colesiota conjunctivae (synonym: Chlamydia psittaci ovis). According to the postulates of Koch Colesiota conjunctivae is a primary cause of contagious keratoconjunctivitis in sheep, but the clinical picture is complex and is a result of the interaction between the infecting chlamydiae, host resistance factors, and secondary infections caused by opportunistic bacterial ocular pathogens. The clinical syndrome might also be caused by other micro-organisms, such as Mycoplasma conjunctivae or environmental factors, such as dust. However, in these cases, cytoplasmatic inclusion bodies cannot be found in the corneal cells of diseased eyes. To differentiate chlamydial keratoconjunctivitis from keratoconjunctivitis due to other causes, it is proposed to include in the name the laboratory findings typical for this disease: Sheep Inclusion Keratoconjunctivitis. Chlamydia are Gram-negative bacteria, which are obligate intracellular parasites. Prolonged treatment seems to be required to eradicate chlamydiae from a host and antibiotics must reach intracellular levels that are higher than their minimum inhibitory concentration for chlamydiae. Tetracyclines are the drugs of choice. This means that for a microbiological cure, diseased sheep must be injected several times a day for a week or more. Because the disease is usually self-limiting and economic losses are considered low, this seems unnecessary and control of the disease by local treatment of secondary infections seems sufficient. However, this will not prevent spreading of the disease in a herd and relapses may occur.

Animals↗

Topical fibronectin in the treatment of keratoconjunctivitis sicca. Chiron Keratoconjunctivitis Sicca Study Group.

Topical fibronectin was evaluated for the treatment of keratoconjunctivitis sicca in a multicenter, double-masked, controlled study in which 272 patients were randomly assigned to treatment. Patients with documented clinical evidence of keratoconjunctivitis sicca received either fibronectin, a vehicle alone, or a commercially available artificial tear. Evaluation at baseline, 21, 42, and 63 days consisted of patient self-evaluation of symptoms, rose bengal and fluorescein staining, tear breakup time, Schirmer's testing, and conjunctival impression cytology. Although all groups showed improvements in most study variables during the course of the study, there were no statistically significant differences found between any of the groups. Topical fibronectin does not appear to be more effective than artificial tears in the treatment of keratoconjunctivitis sicca.

Aged↗

Tear levels of interferon-gamma, interleukin (IL) -2, IL-4 and IL-5 in patients with vernal keratoconjunctivitis, atopic keratoconjunctivitis and allergic conjunctivitis.

BACKGROUND: A predominance of TH2 activity in chronic allergic diseases, such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC), has been suggested recently. However, there is no published study on tear levels of cytokines of the two different subgroups, TH1 and TH2, in patients with ocular allergy. OBJECTIVES: We measured interferon (IFN)-gamma, interleukin (IL)-2, IL-4 and IL-5 levels in tears by ELISA, to determine whether the levels of these cytokines are elevated in allergic ocular diseases when compared among patient groups and normal controls. METHODS: Tear levels of IL-2, IFNgamma, IL-4 and IL-5 were measured by ELISA using samples from patients with VKC, AKC (AKC-NP, without proliferative lesions; and AKC-P, with proliferative lesions), allergic conjunctivitis (AC) and normal subjects. The levels of these cytokines in tears and the clinical severity of AD were also compared. RESULTS: Tear IL-4 level in patients with AKC was significantly higher than those in VKC, AC and controls, and tear IL-4 levels in patients with AKC-P vs VKC differed significantly. Tear IL-5 levels in patients with diseases associated with proliferative lesions, VKC and AKC-P, were higher than those in AC and normal controls. However, tear level of IL-5 in patients with AKC-P was significantly higher than that in AKC-NP. Although the dermatological severity of AD correlated significantly with tear IL-4 level, IFNgamma, IL-2 and IL-5 levels did not correlate with dermatological severity of AD. CONCLUSION: These results indicate that the TH2-like cytokines play an important pathophysiological role in severe ocular allergic conditions such as AKC and VKC and that tear level of IL-5 may be a candidate marker to evaluate the clinical status of ocular allergy. The different patterns of tear levels of IL-4 and IL-5 among ocular allergic diseases may reflect the origin and immunological basis of these cytokines.

Adolescent↗

Spontaneous canine keratoconjunctivitis sicca. A useful model for human keratoconjunctivitis sicca: treatment with cyclosporine eye drops.

Thirty-six sequential cases of canine keratoconjunctivitis sicca (KCS) were treated with ophthalmic cyclosporine. The effects of topical cyclosporine were twofold: (1) cyclosporine increased tear production by 5 mm/min or greater in all cases of spontaneous KCS having an initial Schirmer's Tear Test value greater than 2 mm/min and in 59% of eyes with an initial Schirmer's Tear Test value of 0 to 2 mm/min, and (2) cyclosporine caused marked regression of chronic corneal neovascularization and granulation even in eyes in which lacrimation failed to improve. Additional benefits of topical cyclosporine were reduced mucopurulent conjunctivitis, rapid healing of nonhealing corneal ulcers, and reduced dependence on frequent topical treatments of KCS. Twelve normal beagles treated with topical cyclosporine also had a reversible increase in lacrimation compared with baseline or placebo control-treated dogs.

Animals↗

Keratoconjunctivitis sicca associated with achalasia of the cardia, adrenocortical insufficiency, and lacrimal gland degeneration: Keratoconjunctivitis sicca secondary to lacrimal gland degeneration may parallel degenerative changes in esophageal and adrenocortical function.

OBJECTIVE/DESIGN: This study aimed to examine and describe three siblings with alacrima, the eldest of whom had associated achalasia and adrenocortical insufficiency. PARTICIPANTS: Three affected siblings and four age-matched control subjects participated. INTERVENTION/MAIN OUTCOME MEASURES: The three children underwent complete ophthalmologic examinations; computed tomographic scanning of brain, orbit, chest, and abdomen; and measurement of serum cortisol. All three were subjected to a short synacthen challenge. Lacrimal gland biopsies were performed on the two younger subjects, and specimens were studied by light and electron microscopy. RESULTS: All three children showed virtually absent tear secretion as tested by the Schirmer test. The resulting keratopathy was most severe in the oldest child, who developed bilateral corneal melting. The two younger children showed interpalpebral corneal staining with rose bengal. All three children improved after punctal occlusion. Addison's disease was present in the oldest child. Computed tomographic scanning showed absent lacrimal and shrunken adrenal glands in association with achalasia of the cardia in the oldest child. The lacrimal glands were found to be reduced in size in the next eldest child. When evaluated by electron microscopy, the lacrimal gland biopsy specimens from the two younger children showed neuronal degeneration associated with depletion of secretory granules in the acinar cells. CONCLUSION: In this disease, radiologic evidence of reducing lacrimal gland size with increasing age could represent a degenerative process. This may be paralleled by other signs and the possibility of adrenocortical insufficiency and achalasia of the cardia should be investigated in all children presenting with dry eyes. These children appear to have a progressive neuronal disease.

Adrenal Cortex↗

Conjunctival epithelial cell hypermitosis and goblet cell hyperplasia in atopic keratoconjunctivitis.

Atopic diseases that include eczema (atopic dermatitis), asthma, and seasonal and perennial rhinoconjunctivitis are common manifestations of abnormal immediate hypersensitivity. Ocular involvement, such as atopic keratoconjunctivitis, characteristically includes conjunctival and corneal inflammation, and in a severe form, conjunctival scarring, symblepharon, corneal epitheliopathy, and visual loss. To examine the conjunctival cellular abnormalities in atopic keratoconjunctivitis, we studied the in vivo differentiation and tissue-culture growth characteristics of conjunctiva from normal subjects and patients with severe atopic keratoconjunctivitis. We examined conjunctival biopsy specimens to determine epithelial mitotic rate and goblet cell frequency, and we studied conjunctival explants to determine the latent period for fibroblast outgrowth and fibroblast doubling time. The mitotic rate for atopic keratoconjunctivitis, 6.7% +/- 2.1% (11 patients), was statistically significantly greater than for normal subjects, 2.0% +/- 0.63% (seven subjects) (P = .05). Also the goblet cell frequency for atopic keratoconjunctivitis, 14.6% +/- 3.4% (11 patients), was statistically significantly greater than for normal subjects, 4.8% +/- 0.92% (seven subjects) (P = .02). The latent period for fibroblast outgrowth and the fibroblast doubling time for atopic keratoconjunctivitis were not statistically significantly different from normal control subjects. Therefore, atopic keratoconjunctivitis was associated with conjunctival epithelial hypermitosis, goblet cell hyperplasia, and normal fibroblast tissue-culture growth. These characteristics may be useful in the diagnosis of atopic keratoconjunctivitis. We previously studied another disease characterized by chronic conjunctival inflammation and scarring, cicatricial pemphigoid, which also demonstrated conjunctival epithelial hypermitosis, but in contrast there was near absence of goblet cells, and the fibroblasts were hyperproliferative. These differences may be used to distinguish atopic keratoconjunctivitis from cicatricial pemphigoid.

Aged↗

Topical 0.1% prednisolone lowers nerve growth factor expression in keratoconjunctivitis sicca patients.

PURPOSE: To compare nerve growth factor (NGF) levels in tears and on the ocular surfaces of normal control and non-Sjögren's type keratoconjunctivitis sicca subjects, and to investigate the effect of 0.1% prednisolone eyedrops on NGF levels in keratoconjunctivitis sicca patients. DESIGN: Prospective, double-masked, randomized, comparative clinical trial. PARTICIPANTS: Forty-one keratoconjunctivitis sicca patients and 23 age- and gender-matched healthy subjects. METHODS: Baseline tear NGF levels were measured in keratoconjunctivitis sicca patients and healthy control subjects using enzyme-linked immunosorbent assays. Keratoconjunctivitis sicca patients received 0.1% prednisolone drops in one eye and 0.1% hyaluronic acid drops in the other, 3 times a day for 28 days. Also, impression cytology (IC) and immunostaining for NGF on conjunctival epithelium were performed on both groups. MAIN OUTCOME MEASURES: Tear NGF/total tear protein (TP) concentration ratio, IC and NGF immunocytologic staining, subjective symptom scale, tear breakup time, and Schirmer values. RESULTS: Keratoconjunctivitis sicca patients were found to have baseline tear NGF concentrations higher than those of age- and gender-matched healthy control subjects (65.9+/-14.5 vs. 122.1+/-45.3 pg/mug, P<0.0001). In keratoconjunctivitis sicca patients, prednisolone treatment for 28 days resulted in a decrease in tear NGF levels, symptom scores, and IC scores, whereas hyaluronic acid treatment had no such effect (68.2+/-25.0 pg/mug vs. 108.0+/-43.4 pg/mug, P<0.0001 for tear NGF/TP ratio; 2.16+/-1.01 vs. 3.39+/-1.50, P = 0.0014 for symptom scale; 1.05+/-0.67 vs. 1.61+/-0.86, P = 0.0317 for IC). Measurements taken at both 14 and 28 days indicated that neither prednisolone nor hyaluronic acid treatment affected breakup time or Schirmer values. CONCLUSION: Keratoconjunctivitis sicca patients showed elevated levels of tear NGF, which were decreased by treatment with 0.1% prednisolone. These data suggest that ocular surface NGF may play an important role in ocular surface inflammation processes associated with dry eyes.

Administration, Topical↗

Increased expression of the type 1 growth factor receptor family in the conjunctival epithelium of patients with keratoconjunctivitis sicca.

PURPOSE: To investigate the expression of type 1 growth factor receptors (epidermal growth factor receptor, ErbB2, and ErbB3) in the conjunctival epithelium of patients with keratoconjunctivitis sicca. METHODS: Immunofluorescent staining and Western blotting were performed to grade the level of expression of the epidermal growth factor receptor ErbB2, and ErbB3 in conjunctival epithelial impression cytologies taken from both eyes of seven normal subjects and 22 patients with keratoconjunctivitis sicca. RESULTS: Epidermal growth factor receptor staining was observed in a greater percentage of keratoconjunctivitis sicca than normal samples (P <.05). ErbB2 and ErB3 staining in the apical conjunctival epithelium was observed in both groups, but stronger ErbB2 and ErbB3 staining was noted in keratoconjunctivitis sicca conjunctival samples (P <.05). The relative levels of expression of these receptor proteins on immunoblots were consistent with immunofluorescent staining. On immunoblots, epidermal growth factor receptor protein was detected in 50% of keratoconjunctivitis sicca samples, but none of the normal samples (P <.025). The expression of ErbB2 and ErbB3 on immunoblots was also greater in the keratoconjunctivitis sicca samples (P <.05). Immunofluorescent staining scores for these receptors were correlated with conjunctival lissamine green staining scores (r =. 574, P <.01 for epidermal growth factor receptor; r =.620, P <.0025 for ErbB2; r =.502, P <.025 for ErbB3) and with corneal fluorescein staining (r =.409, P <.05 for ErbB2; r =.588, P <.005 for ErbB3). CONCLUSION: The expression of the type 1 growth factor receptors is significantly greater in the conjunctival epithelium of eyes with keratoconjunctivitis sicca than normal eyes. The increased expression of these receptors was positively correlated with ocular surface dye staining. The increased expression of these receptors may contribute to the abnormal growth and differentiation of the conjunctival epithelium that occurs in keratoconjunctivitis sicca.

Adult↗

Bacteriological investigation of infectious keratoconjunctivitis in Norwegian sheep.

Contagious keratoconjunctivitis is a rather common disease in Norwegian sheep. Since the knowledge of its aetiology is limited, the present study was performed to determine the microorganisms involved. Local veterinarians throughout the country collected conjunctival swabs from both sick (n = 43) and healthy (n = 42) sheep on 15 farms with outbreaks of ovine keratoconjunctivitis, and further from healthy sheep (n = 50) on 17 farms not showing any signs of conjunctival disease. All samples were cultivated for bacteria and mycoplasma. Listeria monocytogenes was isolated from 3 cases (1%) in one single herd. Staphylococcus aureus (5%), Corynebacterium spp. (2%) and Escherichia coli (4%) were isolated only in herds with keratoconjunctivitis, but from both sick and healthy animals. Moraxella (Branhamella) ovis was isolated from 28% of sampled animals in affected herds and from 10% of sampled animals in healthy herds. The corresponding numbers for Moraxella spp. were 9%/12%, for Pseudomonas spp. 7%/8%, for Staphylococcus spp. 22//22%, for Bacillus spp. 12%/14%, for Micrococcus spp. 6%/2% and for Streptococcus/Enterococcus spp. 2%/2%. Mycoplasma conjunctivae was isolated from 16 animals with keratoconjunctivitis (37%) and from 3 animals without clinical signs (7%) in farms with keratoconjunctivitis. In farms without clinical signs of keratoconjunctivitis, M. conjunctivae was isolated in 4 animals (8%). To our knowledge, this is the first time M. conjunctivae has been isolated in Norway. Other predisposing agents found were Moraxella (Branhamella) ovis and Listeria monocytogenes. The etiological importance of different microorganisms in ovine keratoconjunctivitis seems to vary; some are probably only present as secondary invaders. Other possible causes of ovine keratoconjunctivitis in Norway, such as Chlamydia psittaci, remain to be investigated.

Animals↗

Increased plasma levels of nerve growth factor in vernal keratoconjunctivitis and relationship to conjunctival mast cells.

PURPOSE: To evaluate the nerve growth factor (NGF) plasma concentration in patients with vernal keratoconjunctivitis and to correlate it with the histopathology and immunopathology of the disease. METHODS: An immunoenzymatic assay was performed to measure NGF plasma levels in patients with vernal keratoconjunctivitis and in healthy matched controls. A competitive radioimmunoassay was used to detect eosinophil cationic protein (ECP) and total specific immunoglobulin E (IgE) serum levels. Histologic evaluation was performed in tarsal and bulbar conjunctival biopsies. RESULTS: Plasma levels of NGF were significantly higher (P < 0.001) in patients with vernal keratoconjunctivitis (mean = 8224.47 +/- 7802.53 pg/ml; median = 121 pg/ml) than in controls (mean = 51.68 +/- 5.94 pg/ml; median 42.5 pg/ml). Conjunctival tissue showed a significant increase of mast cells, eosinophils, and lymphocytes in vernal keratoconjunctivitis. A significant correlation was observed between plasma levels of NGF and the number of mast cells in the tarsal conjunctiva (Cc = 0.81; P < 0.005) and bulbar conjunctiva (Cc = 0.77; P < 0.01) of patients with vernal keratoconjunctivitis. No correlation was found between NGF plasma levels and total IgE serum levels in patients with vernal keratoconjunctivitis; NGF plasma levels were inversely related to the number of circulating eosinophils (Cc = -0.61; P < 0.05) and to the increased serum levels of ECP (Cc = -0.71; P < 0.02). CONCLUSIONS: These data represent the first reported evidence of increased NGF plasma levels in an allergic human disease and suggest a possible relationship between this neurotrophic polypeptide and inflammatory cells in vernal keratoconjunctivitis.

Adolescent↗

[Tear lactoferrin in keratoconjunctivitis sicca].

Keratoconjunctivitis sicca is a commonly encountered disease with decreased lacrimal gland activity. There are several tests to determine the lacrimal gland function, but all have limitations in accuracy, sensitivity or technical difficulty. At present, there is no reliable objective test to render a firm diagnosis of dry eye. Lactoferrin is one of the major proteins secreted by the lacrimal gland. Its concentration was found to correlate well to lacrimal gland activity. In this study we tried to evaluate the diagnostic value of lactoferrin measurement in comparison with other tests for keratoconjunctivitis sicca. Tests including the measurement of tear lactoferrin, Schirmer's-1 test, Schirmer's basal test, tear film break-up time, and rose bengal stain of the cornea were done on 60 healthy eyes and 56 eyes with keratoconjunctivitis sicca. The lactoferrin level was measured by a commercially available "Lactoplate" (Eagle Vision, U.S.A.). It is a plate containing gel loaded with rabbit anti-human-lactoferrin antiserum. Tear-moistened filter paper discs containing lactoferrin were placed on the gel. The lactoferrin concentration could be determined by measuring the concentric ring of precipitate after 72 hours incubation at room temperature. The average concentration of lactoferrin was 1.9 +/- 0.51 mg/ml in the normal group and 1.4 +/- 0.93 mg/ml in the keratoconjunctivitis sicca group. They were significantly different from each other (t-test: p less than 0.05). The results of the other 4 tests also showed a significant difference between the normal and keratoconjunctivitis sicca group, but the lactoferrin measurement had the highest specificity among these 5 tests. Because of the technical simplicity of measurement and its high specificity, lactoferrin measurement could be a valuable tool for the early and accurate diagnosis of keratoconjunctivitis sicca.

Adult↗

Putative quantitative trait loci associated with the probability of contracting infectious bovine keratoconjunctivitis.

Infectious bovine keratoconjunctivitis, also known as pinkeye, is an economically important disease in cattle. The objective of this study was to detect QTL associated with infectious bovine keratoconjunctivitis in offspring from a Brahman x Hereford sire. The sire was mated to Hereford, Angus, and F1 cows to produce 288 offspring in 1994 and mated to MARC III ((1/4) Hereford, (1/4) Angus, (1/4) Red Poll, and (1/4) Pinzgauer) cows in 1996 to produce 259 offspring (547 animals total). Infectious bovine keratoconjunctivitis was diagnosed by physical examination in 36 animals of the family. Records included unilateral and bilateral frequency, but not severity. Records were binary: 0 for unaffected and 1 for affected cattle. A putative QTL for infectious bovine keratoconjunctivitis was identified on chromosome 1, with a maximum F-statistic (F = 10.15; P = 0.0015) at centimorgan 79 of the linkage group. The support interval spanned centimorgans 66 to 110. There was also evidence suggesting the presence of a QTL for infectious bovine keratoconjunctivitis on chromosome 20, with a maximum F-statistic (F = 10.35; P = 0.0014) at centimorgan 16 of the linkage group. The support interval ranged from centimorgan 2 to 35. This report provides the initial evidence of QTL for infectious bovine keratoconjunctivitis. Although a candidate gene was identified for one of the regions of interest, further studies are needed to identify the genetic basis of resistance to the disease.

Animals↗

Late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation: incidence and risk factors. European Group or Blood and Marrow Transplantation (EBMT) Working Party on Late Effects.

The incidence, time course and risk factors associated with late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation (BMT) was evaluated in a multicenter retrospective cohort study conducted by the European Group for Blood and Marrow Transplantation (EBMT) Working Party on Late Effects. Data were requested from participating European centers on all patients transplanted up to December 1980 and on all patients treated during the year of 1984. Twenty-eight centers reported data on 258 patients and 248 could be evaluated for keratoconjunctivitis. Forty-eight of the 248 (19%) patients developed a keratoconjunctivitis sicca syndrome between 3 and 127 months (13.8 months) after BMT. The actuarial probability of developing dry eyes was 21 +/- 3% at 15 years. Thirty-three of the 48 (69%) patients with sicca syndrome had graft-versus-host disease (GVHD) compared to 60 of 200 (30%) patients without keratoconjunctivitis (P < 0.0001). The probability of developing keratoconjunctivitis sicca syndrome at 15 years was 38 +/- 6% for patients with and 10 +/- 3% (P < 0.0001) for those without chronic GVHD. Factors associated with an increased risk for late-onset of keratoconjunctivitis are chronic GVHD (relative risk 3.5; CI, 1.9-6.9), female patients (5.6; CI, 1.6-18.8), age older than 20 years (3.1; CI, 1.6-5.6), single dose irradiation for preparation to BMT (3.8; CI, 1.3-11.3) and methotrexate for prevention of GVHD (3.6, CI, 1.05-12.8). Late-onset kerato- conjunctivitis is a frequent ocular complication of BMT. With adequate treatment, severe corneal defects can be avoided. It occurs more frequently in patients with chronic GVHD, but, independent of chronic GVHD, more frequently in older patients and in females as it is observed in de novo Sjögren's syndrome. These data support the current concept that chronic GVHD is a reaction of both, allo- and autoimmunity.

Adolescent↗