Results

STUDY ENTRANCE

Of the 106 patients at entry 73% were females. There were statistically significantly more females in the PSS patient group compared with the other two patient groups—93% versus 58% for KCS-SSS and 66% for KCS-NS (Table 1). The average age was 53.5 years and the mean duration of the dry eye status judged from the beginning of ocular discomfort was 3.9 years. No statistically significant differences in mean age and mean duration of disease were noticed between the three patient groups. Based on the criteria of Daniels and Talal,16 31 patients had KCS associated with PSS, 19 had KCS-SSS, and 56 patients had KCS-NS. Extensive ophthalmic examination revealed no cause of KCS in the KCS-NS patient group. Of the 19 KCS-SSS patients 11 had rheumatoid arthritis, four had systemic sclerosis, two had dermatomyositis, and two had systemic lupus erythematosus.

Signs and symptoms

No statistically significant differences between the three groups were found with regard to the symptoms and signs with the exception of suffering from a sandy feeling in the eyes. This symptom was reported in more than 80% of KCS-PSS and KCS-NS patients, but in only 53% of the KCS-SSS patients. At the time of the last examination none of the patients had major corneal, scleral, or choroidal complications.

Tear function tests

The lysozyme tear fluid concentrations in all three patient groups were well below the limit of 1400 μg/ml (Table1). Lowest values were found in the KCS-PSS patient group, and no significant differences were noted between the KCS-SSS and the KCS-NS patient groups (Table1). In the KCS-PSS patient group the Schirmer test values were low when compared with the other groups, whereas in this patient group highest values of the rose bengal test were noted (Table 1).

STUDY FOLLOW UP

After a 10 year period 71 patients were evaluable for follow up (Table 2). Owing to a variety of reasons 35 patients had dropped out: 24 patients had died, seven patients were unwilling to participate in the study, and four patients were lost for follow up as a result of moving to another location.13 At baseline no differences in ophthalmic variables were found between patients not evaluable for follow up and patients who were, with exception of suffering from a sandy feeling in the eyes. In patients who dropped out this symptom was present in 62%, whereas 84% of the patients who also were evaluable at follow up reported this complaint (p <0.05) (data not shown). Of the remaining 71 patients 21 had KCS-PSS, 12 patients had KCS-SSS, and 38 patients had KCS-NS. Data of these patients are shown in Table 3. At the time of examination none of these patients had major ocular complications.

Signs and symptoms

At follow up no statistically significant differences in signs and symptoms between the three patient groups were noted (Table 3).

Tear function tests

In the 10 year period the KCS-PSS patient group remained essentially the same. The KCS-SSS group showed a tendency to improvement (Table 4). The patients in the KCS-NS group showed a significant and sizeable improvement in both symptoms and signs.

At follow up, again the KCS-PSS patient group showed the poorest tear function, the mean values of all variables, including tear fluid lactoferrin concentration, being within the pathological range. At follow up in the KCS-SSS and the KCS-NS patient groups, mean Schirmer-I test values and mean lysozyme and lactoferrin concentrations were within the normal range, but the tear film break up time values were poor.

Discussion

After an obvious initial period a remarkable steady state situation in ocular findings as well as general situation in the KCS-PSS patient group was observed.13

Within the KCS-SSS group the tear gland function variables reached the normal range at follow up. As secondary Sjögren’s syndrome represents a heterogeneous group of patients, remission of the underlying disease may have similar consequences for the ocular findings.

In contrast with our expectation of a steady state situation in the KCS-NS patient group a marked improvement of the tear function variables was noted. At follow up tear gland function variables reached the normal range, and some symptoms disappeared. The most common and, in fact, unavoidable situation leading to a dry eye state is assumed to be advanced age: the age related dry eye. In itself age related alterations of the lacrimal gland do not necessarily cause a dry eye unless the tear function was marginal to begin with. In a few documented cases of these so called age related dry eyes histopathological atrophy of the secretory elements and the lymph follicles of the eye and an increase of fibrous tissue as well as plasmacytic infiltration have been reported.19 In sublabial salivary gland biopsy specimens similar findings have been seen.20 In a small series, abnormal lacrimal gland histology including lymphocytic infiltration and an increase in fibrous tissue was observed not only in Sjögren’s syndrome patients, but also in KCS-NS patients.21 In contrast, in bulbar conjunctiva biopsy specimens from a normal elderly population morphological changes including irregularities in thickness of the epithelium were observed exclusively in patients over 80 years old.22 In Sjögren’s syndrome patients as well as KCS-NS patients bulbar conjunctiva biopsy specimens revealed stratification of the conjunctival epithelium with separation of the superficial cell layers, directly proportional to the clinical severity of the disease.23 After nasolacrimal duct occlusion in two of these KCS-NS patients a reduction in epithelial cell stratification was noticed.23

At advancing age in healthy individuals a gradual decrease in tear secretion as measured by the Schirmer-I test has been demonstrated in both males and females. Also, a decrease in tear fluid lysozyme concentration has been shown.24 In view of the findings of a significant overall improvement of tear gland function in the present study we favour avoiding the term ‘age related KCS’. But the explanation of this phenomenon is difficult. One could speculate on a possible role of previous subclinical dacryoadenitis. Also intermittent focal adenitis of the lacrimal glands cannot be excluded.21-23 However, because in healthy salivary gland tissue focal lymphocytic adenitis has been described,25 a temporary decrease in tear secretion due to intermittent lacrimal adenitis is at least a doubtful theory.

In conclusion, within the population of dry eye patients, referred to a university hospital ophthalmic outpatients’ department specialising in the dry eye syndrome, a considerable number of patients appears to suffer from Sjögren’s syndrome. Tear gland function in PSS patients is characterised by a steady state situation. In KCS-SSS patients a normalisation of tear gland function variables at follow up was noted. In view of an overall improvement of tear gland function in KCS-NS patients seen over the years we suggest avoiding the term ‘age related KCS’.