Schirmer test values and lysozyme content of tears in acute dendritic keratitis.

In acute dendritic keratitis, the lacrimal flow is increased in the affected eye but not in the normal fellow eye. After recovery the tearflow returns to normal. The lysozyme concentration in the affected and the normal fellow eye do not differ statistically significantly nor do they differ significantly from values of an age- and sex-matched control group. There is no correlation between tearflow and lysozyme concentration. These findings support the view of a constant composition of stimulated tear fluid, irrespective of tear volume produced.

Origin and biosynthesis of human tear fluid proteins.

In tear fluid, a large number of proteins can be detected with electrophoretic or immunologic techniques. The composition of serum proteins in tears resembles that of whole serum. By comparison of the protein patterns resulting from different sampling methods, it was shown that serum albumin is not present in the secretion of the lacrimal gland, but is mixed with the tear fluid in the conjunctival sac. The in vitro synthesis and excretion of more than 20 protein components by the lacrimal gland could be demonstrated. Among these were lactoferrin, tear-specific prealbumin, lysozyme, and secretory IgA. The complexity of the electrophoretic protein pattern of tear fluid can be explained from the combination of the secretory activity of the lacrimal gland and the leakage of serum proteins from the circulation into the tear fluid.

Nonlysozyme antibacterial factor in human tears. Fact or fiction?

The existence of nonlysozyme antibacterial activity in tear fluid was reinvestigated. Tear fluid was fractionated by ultrafiltration and affinity chromatography. The antibacterial activity, detected in native tear fluid, coincided with the presence of lysozyme in the fractions. No antibacterial activity could be detected by agar diffusion in the fractions that should contain the low molecular mass antibacterial factors of tear fluid, reported in the literature.

Combination therapy of recombinant human alpha 2 interferon and acyclovir in the treatment of herpes simplex keratitis.

No statistical difference was found in both partial and complete healing time in acute epithelial herpetic keratitis between the ACV-recombinant human alpha 2 IFN (both "eyedrops" and "eyerods") and Buffy coat human leucocyte alpha IFN. A highly significant difference was found in both partial and complete healing time between the ACV-IFN combination versus the ACV-Placebo combination. The combination of ACV and recombinant human alpha 2 arg IFN is a potent anti-herpetic treatment.

Combination therapy for dendritic keratitis with acyclovir and alpha-interferon.

Fifty-nine patients with superficial herpetic keratitis were treated with 3% acyclovir ointment five times a day in combination with alpha-interferon (30 million IU/mL) or albumin-placebo once a day in a stratified double-masked clinical trial. All patients had minimal wiping of the superficial lesion to isolate virus. The healing time of the corneal ulcers was substantially lower with the combination of acyclovir and interferon than with the combination of acyclovir and placebo. Only minor toxic effects were observed. The combination of acyclovir and interferon appears to be the best presently known treatment for dendritic keratitis.

A new intermediate adenovirus type causing conjunctivitis.

A new adenovirus of intermediate type involved in conjunctivitis has been isolated. The virus is related to adenovirus types 13 and 30 by neutralization and to types 10 and 19 by hemagglutination inhibition. Since 1976 the agent has been causing sporadic cases of conjunctivitis in different parts of The Netherlands. Twenty-three cases have been established by virus isolation from the affected eyes. The symptoms of the disease range from epidemic keratoconjunctivitis to pharyngoconjunctival fever. Also, adenovirus type 13-30/10-19 has been isolated from the cervix uteri of four women in a series of 1,477 women with cervicitis.

Lipolytic activity of Staphylococcus aureus from different sources.

The lipolytic activity for a number of triglycerides, oils, and Tween 80 of 50 Staphylococcus aureus strains from the margin of the eyelids in patients with chronic blepharitis was found to be significantly greater than that of 80 S. aureus strains from the upper respiratory tract.

Central corneal abscess.

Central corneal abscess developed in the experimental animal after inoculation of biologically active staphylococcal strains in a paracentral epithelial lesion of the cornea. These abscesses did not ulcerate, developed only with high inocula, occurred more frequently in immunized rabbits. A serpiginous type of ulceration did not develop at the site of the initial epithelial lesion nor at any other place in the cornea. Histologically, the lesions consisted of densely packed polymorphonuclear leukocytes between the corneal lamellae.

Comparison of electrophoretic techniques for the analysis of human tear fluid proteins.

Five electrophoretic techniques were tested for application to the analysis of human tear proteins: disc-, SDS- and gradient polyacrylamide gel electrophoresis, immunoelectrophoresis and isoelectric focusing. Protein patterns obtained from pooled normal tear fluid, tear fluid from keratoconjunctivitis sicca patients and from patients with chronic non-infectious conjunctivitis were compared. The four major components of human tear fluid were purified and their positions within the separation patterns were determined. The highest resolution and the clearest differences between the patterns of the three tear samples were obtained by SDS polyacrylamide gel electrophoresis.

Immunochemical determination of human tear lysozyme (muramidase) in keratoconjunctivitis sicca.

Radial immunodiffusion was tested as an alternative for the agar diffusion assay for lysozyme in tear fluid. The influence of interactions between lysozyme and agarose or filter paper, used for sample collection, on the results of the immunodiffusion test was investigated. In 100 tear samples from 50 healthy volunteers and average lysozyme concentration of 1.9 g/l was found. Lysozyme values obtained by both methods in the tear fluid of a group of 78 volunteers, ranging from healthy individuals to severe keratoconjunctivitis sicca patients were compared. A lower limit of normal at 1.1 g/l was found by the radial immunodiffusion assay.

Trifluorothymidine versus adenine arabinoside in the treatment of herpes simplex keratitis.

Trifluorothymidine (TFT) and adenine arabinoside (ara-A) are effective antiviral drugs with a very low toxicity for the cornea. In our study no difference between these 2 drugs in antiviral activity was noted. The average healing time for TFT was 11-14 days and for ara-A 10-54 days. These data differ markedly from those of other studies. This was the result of the use of additional criteria for healing of the lesion. Not only absence of fluorescein staining of the cornea but also the absence of oedema and cystic changes in the epithelium over the previous ulcer were considered criteria for healing. In addition to clearly defined healing criteria and the healing time we found the interval between the first symptoms and the commencement of the therapy of greatest importance in the clinical evaluation of antiviral drug efficacy. An effort was made to approximate this relationship for TFT and ara-A mathematically.

Limbal and corneal calcification in patients with chronic renal failure.

In patients with chronic renal failure on regular dialysis treatment, limboconjunctival degenerations and calcifications are commonly observed. In this study three groups of patients were followed over a period of 6 years. The first group consisted of 47 patients with renal failure, the second group of 17 patients with renal failure and hyperparathyroidism not controlled by drugs, and the third group seven patients with primary hyperparathyroidism without renal failure. The aim of this study was to determine the progression of the limboconjunctival changes over time. The hypothesis that an increase in serum calcium and phosphorus concentrations, as a result of tertiary hyperparathyroidism, could possibly add a corneal component to the limbal calcification was also tested. All patients with renal failure (in as much as the degenerative limbal features were not obscured by deposits of lime salts), had a type II white limbus girdle of Vogt. This limbal degeneration was observed in only 45% of controls. In all 47 patients with renal failure conjunctival calcification was observed; 26 of them also had limbal calcification. After 6 years 41 patients had developed limbal calcification. This progression was statistically significant. In 15 out of 17 patients with tertiary hyperparathyroidism a band-shaped keratopathy developed in addition to the limboconjunctival calcification.

Nocardia gypsoides corneal ulcer.

Nocardia gypsoides, a species characterised by its ability to produce calcium sulphate granules, has been isolated for the first time from a corneal ulcer. In vivo this pseudomycete also forms gypsum. Every effort should be made to identify Actinomycetales to species level. The names Leptothrix and Streptothrix should be abandoned.

The red eye of renal failure: a crystal induced inflammation?

Of 57 patients with chronic renal failure and calcification of the anterior membranes of the eye eight developed inflammatory reactions, clinically indistinguishable from pingueculitis. In three patients an acute inflammatory reaction of the episcleral tissue and the conjunctiva over it developed which we considered to represent the red eye of renal failure. In these patients massive shedding of calcium phosphate salts was clinically evident. Histopathologically in all these patients calcific deposits were observed. Although sporadically polymorphonuclear leucocytes were present in the inflamed tissues we could not demonstrate crystal phagocytosis. We believe that in the red eyes in renal failure and, more specifically, in the red eyes of renal failure a crystal induced inflammatory mechanism is not operative.

Red eyes in renal failure.

Of 57 patients with chronic renal failure who all had deposition of calcium salts in the conjunctival and corneal tissue two developed a brief episode of painful irritation and redness of the conjunctiva and subconjunctiva. This hyperaemia was adjacent to erosions of the corneal epithelium of the eye as a consequence of exfoliation of calcium concretions from the superficial corneal epithelium. Eight patients showed inflammatory reactions of the conjunctivae that were clinically identical to inflamed pingueculae. Three patients showed an inflammatory reaction of the eye that was characterised by a waxy red, more or less diffuse, episcleral and conjunctival hyperaemia extending beyond the palpebral fissure. The average value of the serum calcium concentration in these patients was particularly high and statistically significantly higher than in patients with calcification but without inflammatory signs and also higher than in patients who showed pingueculitis. We propose to reserve the term 'red eye of renal failure' for the latter group of patients.

Bromovinyldeoxyuridine and interferon treatment in ulcerative herpetic keratitis: a double masked study.

Bromovinyldeoxyuridine is a potent and safe antiherpes compound that in combination with a placebo treatment promoted the partial and complete healing of herpetic epithelial disease in 22 patients in average times of 4-6 days and 8.5 days respectively. However, when BVDU was combined with 1.5 X 10(6) IU of recombinant a 2C interferon, partial and complete healing times for keratitis in 19 patients were reduced to 2-6 days and 4-6 days respectively. No toxic effects of the medications were observed in any patient.

Long-term course of tear gland function in patients with keratoconjunctivitis sicca and Sjögren's syndrome.

AIMS: To assess the course of tear gland function of patients with keratoconjunctivitis sicca (KCS) associated with primary (KCS-PSS) or secondary Sjögren's syndrome (KCS-SSS), and of patients with KCS not related to Sjögren's syndrome (KCS-NS). METHODS: In 106 patients with dry eye an ophthalmic diagnosis of KCS was made. Subsequent evaluations revealed a diagnosis of KCS-PSS in 31, KCS-SS in 19, and KCS-NS in 56 patients. Follow up assessments have been performed 10-12 years after initial diagnosis. RESULTS: At baseline and at follow up tear gland function tests were worse in patients with KCS-PSS compared with the other forms of KCS. At follow up in the KCS-SSS patient group the tear gland function variables returned to marginal normal limits. In contrast with expectation, a marked improvement of the tear gland function variables in the KCS-NS patient group was noted. CONCLUSIONS: In KCS-PSS patients tear gland function is characterised by a steady state situation. In KCS-SSS patients the normalisation of tear gland function variables most probably reflects a remission of the underlying disease. In view of the overall improvement in KCS-NS patients the term age related KCS should be avoided.

Diagnosis and differential diagnosis of keratoconjunctivitis sicca associated with tear gland degeneration.

The clinical tests to diagnose keratoconjunctivitis sicca are weak, whereas the laboratory tests are very powerful, but there is no reason whatsoever to discard the present clinical tests. For example, finding a Schirmer test consistently lower than 5 mm is an easy way to strongly suspect a dry eye state. The level of tear fluid production can help one to determine the preferred viscosity of the tear substitute. Then, what test should be used other than the rose Bengal test to evaluate the over-all effect of the dry eye state on the external eye? What other test than the break-up time is there to evaluate tear film stability? There is no doubt that laboratory tests will be used in the future as routine clinical procedures, in addition to but not replacing the clinical tests, as the tear protein concentration, the Schirmer test values and the break-up time are important for the diagnosis of dry eye and, analyzed together, they may be of value to differentiate between Sjögren's and non-Sjögren's keratoconjunctivitis sicca.

Sjögren's syndrome and tear function parameters.

In a group of patients with keratoconjunctivitis sicca associated with Sjögren's syndrome, the Schirmer values were lower in the Sjögren group of patients in comparison with a comparable group in which KCS was not associated with any systemic disease and these differences reached almost statistical significance. But a significant decrease in tear fluid lactoferrin concentration and tear film break-up time was demonstrated. The combination of the tear fluid lactoferrin concentration, the Schirmer I test values and the tear film break-up time provides a basis for differential diagnosis that is of some value clinically. None of these parameters in itself appeared to be of any clinical value to differentiate between KCS patients who were or were not associated with Sjögren' syndrome.

Sjögren's syndrome: terminology.

In spite of our continuously improved pathobiological understanding, there is still no consensus on terminology and disease criteria in Sjögren's syndrome (SS). This survey points out discrepencies in the current description of the syndrome, and argues for a new classification model. We suggest that the present nomenclatures for the global disease (Sjögren's disease) and disease subsets (primary and secondary SS) be retained until additional pathobiological insights give rise to new and descriptive terms. We do find evidence, however, to support a new terminology and classification of the main immunoinflammatory manifestations of primary SS. Accordingly, three "exocrine" and four "non-exocrine" subgroups of disease manifestations are here defined. The usefulness of the proposed model should be evaluated in clinical studies and in a debate engaging all of the medical specialities involved.