R. J. W. De Keizer

Effect of timolol with and without preservative on the basal tear turnover in glaucoma.

AIMS--The purpose of this study was to assess whether the preservative benzalkonium chloride (BAC 0.01%) present in timolol induced a decrease in basal tear turnover and a deterioration of precorneal tear film in patients with glaucoma and ocular hypertension using topical timolol. METHODS--The basal tear turnover of 20 patients with open angle glaucoma or ocular hypertension was measured by computerised objective fluorophotometry when using topical timolol preserved with BAC and 2 weeks after changing to topical timolol containing no preservative. Evaluation of the precorneal tear film was done by measuring the break up time (BUT) before and 2 weeks after changing medication. RESULTS--The tear turnover of the patients before the change was 32% lower than that of healthy controls (mean tear turnover values (SD) (%/min): 10.7 (3.0) and 15.6 (5.4), respectively, p < 0.0001). A mean increase of 28% (47%) in the individual tear turnover values was found after the change to the preservative-free timolol (p = 0.04). The BUT values before the change of medication did not differ significantly from those after the change (p = 0.5) but both values were significantly lower than the values of healthy controls (p = 0.009 and p = 0.003, respectively). CONCLUSION--Preservative-free timolol solution has a favourable effect on the tear turnover of patients with glaucoma and ocular hypertension in comparison with timolol containing BAC. The integrity of the precorneal tear film persisted to be affected when using timolol without BAC. Timolol without preservative can be recommended in those patients who have keratoconjunctivitis sicca or a borderline tear production since BAC may exacerbate a dry eye state.

Topical application of 5-Fluorouracil in premalignant lesions of cornea, conjunctiva and eyelid

Local application of 5-Fluorouracil was practised on 5 patients. In 3 patients with multiple premalignant oculo-cutaneous lesions, two of whom had also premalignant epibulbar lesions, local 5% 5-Fu cream and/or 1% 5-Fu eyedrops were applied. In 2 other patients who had only premalignant lesions on the cornea and conjunctiva, 1% 5-Fu eyedrops were used only. In animal experiments 1% 5-Fu was not found to cause any damage to normal corneal and conjunctival epithelium. The frequency of the applications and the duration of the treatment were dependent on the location and extent of the lesions. Except for easily treatable lesions, caused by the separation of the tumour epithelium, no complications of local 5-Fu treatment were seen. The visual acuity improved in all 4 patients in whom the cornea was affected. In these premalignant conditions the diagnosis and assessment of the therapy were based on exfoliative cytology and biopsies.

Pterygium excision with or without postoperative irradiation, a double-blind study

A double-blind study (covering 40 months) of 40 eyes with a pterygium which had not previously been operated on, was carried out to study the effect of postoperative irradiation. Nineteen eyes were treated by the ‘bare sclera’ operation technique only and in 13 cases (68%) a recurrence occurred within 4 months. In 18 eyes from the group of patients treated with Sr 90 irradiation on the 1st, 7th and 14th postoperative day (maximum 3×1000 rad) no recurrences were seen.Patients with a recurrent pterygium and diplopia, symblepharon, visual disturbances (growth over the pupil or severe astigmatism) or many previous operations, were treated by lamellar keratoplasty (Dake, 1980). The recurrences without these complications were treated with success by the ‘bare sclera’ technique and postoperative irradiation.Complications did not occur in any of the series.

Increased presence of Epstein–Barr virus DNA in ocular fluid samples from HIV negative immunocompromised patients with uveitis

AIMS To investigate whether routine testing for Epstein–Barr virus (EBV) is necessary in the examination of a patient with uveitis. METHODS Intraocular EBV DNA was determined in 183 ocular fluid samples taken from patients with AIDS and uveitis, HIV negative immunocompromised uveitis, acute retinal necrosis, toxoplasma chorioretinitis, intraocular lymphoma, anterior uveitis, and miscellaneous uveitis of unknown cause. In 82 samples from this group of patients paired serum/ocular fluid analysis was performed to detect local antibody production against EBV. Controls (n=46) included ocular fluid samples taken during surgery for diabetic retinopathy, macular pucker, or cataract. RESULTS Serum antibody titres to EBV capsid antigen proved to be significantly increased in HIV negative immunocompromised patients with uveitis (p<0.01) compared with controls. Local antibody production revealed only three positive cases out of 82 patients tested, two results were borderline positive and one patient had uveitis caused by VZV. EBV DNA was detected in three out of 46 control ocular fluid samples. In the different uveitis groups EBV DNA was noted, but was not significantly higher than in the controls, except in six out of 11 HIV negative immunocompromised patients (p=0.0008). In four out of these six cases another infectious agent (VZV, HSV, CMV, or Toxoplasma gondii) had previously been identified as the cause of the uveitis. CONCLUSIONS When comparing various groups of uveitis patients, EBV DNA was found more often in HIV negative immunocompromised patients with uveitis. Testing for EBV does not have to be included in the routine management of patients with uveitis, since indications for an important role of this virus were not found in the pathogenesis of intraocular inflammation.

Syringomatous carcinoma of the eyelid and orbit: a clinical and histopathological challenge

AIMS To present three patients with a syringomatous carcinoma (SC). SC is a rare cutaneous neoplasm, most frequently situated on the face and scalp and histologically characterised by an infiltrative pattern of basaloid or squamous cells, a desmoplastic stromal reaction, keratin filled cysts, and granular structures. METHODS The clinical histories of the patients with a SC were investigated retrospectively. RESULTS Patient 1 had a benign appearing tumour of the lower eyelid. Five tumour excisions were necessary to remove the SC completely. Patient 2 had a tumour on the lateral part of the lower eyelid and in the medial canthal area. The histopathological findings revealed a squamous cell carcinoma, later revised as a SC. In spite of two excisions and one microscopically controlled excision, a recurrence occurred. An exenteration orbitae was recommended. Patient 3, known to have a history of multiple malignant skin tumours after kidney transplantation and use of cyclosporin, presented with a firm mass in the eyebrow region and in the nasal area of the orbit. The pathological diagnosis of this adnexal tumour was difficult. An exenteration was recommended. CONCLUSIONS SC is a benign appearing but extremely invasive, locally destructive, slowly growing adnexal tumour, derived from eccrine sweat glands. It is often mistaken, both clinically and microscopically, for other benign and malignant entities. The tumour recurrence is high due to extensive perineural invasion, but regional or distant metastases are rare. The local aggressive nature of the tumour and the high recurrence rate may necessitate mutilating procedures. Optimal treatment consists of a complete microscopically controlled surgical excision with clear surgical margins.

Immunophenotypic markers to differentiate between benign and malignant melanocytic lesions

Background/aims: The authors investigated the expression of S100A1, S100A6, S100B, MelanA, and CEA in conjunctival naevi, primary acquired melanosis (PAM), conjunctival melanoma, and uveal melanoma in order to assess their potential usefulness in the pathological differential diagnosis of these entities. Methods: Paraffin embedded sections of 18 conjunctival naevi, 14 PAM, 16 conjunctival melanomas, and 20 uveal melanomas were immunostained for S100A1, S100A6, S100B, MelanA, and CEA, and expression was scored semiquantitatively. Results: Expression of S100A1 differed significantly between conjunctival naevi and conjunctival melanoma, with percentages of positive cells of 30.6% and 71.4%, respectively. Conjunctival melanomas had high average scores for S100A1 and S100B (71.4%, 62.9%, respectively), while uveal melanomas also had high S100A1 but low S100B scores (88.5%, 18.5%, respectively). MelanA was highly variable; naevi and uveal melanoma had higher average scores than conjunctival melanoma. CEA was hardly detectable in all four groups. Conclusion: S100A1 seems to be a possible candidate to differentiate conjunctival naevi from conjunctival melanoma. S100B seems to differentiate between uveal melanoma and conjunctival melanoma. However, the study size was small and therefore the data have to be confirmed by others.

Secretory IgA and lysozyme in tears of patients with Graves' ophthalmopathy

Using an enzyme linked immuno-assay (ELISA) and spectrophotometry, we determined levels of secretory IgA and lysozyme in tears of 69 patients with Graves ophthalmopathy and 28 controls. The quantitative determination of secretory IgA and lysozyme in tears provided an impression of the functioning of the lacrimal gland in the two groups. An IgA/lysozyme ratio was calculated in both patients and controls as a parameter for the activity of the secretory IgA-producing plasma cells in the lacrimal gland. An increase in the IgA/ lysozyme ratio was observed in 23 patients (33%) and one control (3%). Half of the patients who had suffered from the disease for more than 5 years showed a raised IgA/lysozyme ratio. No correlation was found between the IgA/lysozyme ratio and the NOSPECS classification. Our findings suggest that the lacrimal gland is involved in the orbital condition produced by Graves ophthalmopathy. In most cases the involvement occurs in patients with a long history of the disease.

Optic glioma with intraocular tumor and seeding in a child with neurofibromatosis

We treated a 3-year-old boy with neurofibromatosis who had an optic glioma, intraocular extension with seeding, and iris tumors. On the basis of results of ultrasonography, computed tomography, magnetic resonance imaging, and fine needle aspiration, other intraocular and orbital tumors were excluded. Because of the malignant intraocular aspect, the optic nerve glioma was extirpated. Histologic examination confirmed the diagnosis of an optic nerve glioma with intraocular extension, seeding, and iris nodules. In this juvenile pilocytic astrocytoma with secondary perineural fibrous hyperplasia, several mitoses were found in the orbital and intraocular parts. In the optic canal, three small islands were found that were compatible with the diagnosis of malignant astrocytoma, grade 3. The iris nevi appeared as iris pits and not like the Lisch nodules typical of neurofibromatosis. Café au lait spots were present on the skin. The family history was positive for neurofibromatosis. The results of this study demonstrate that optic gliomas are true astrocytomas and not hamartomas, and have a continuous scale from benign to malignant differentiation.

Birdshot Chorioretinopathy and Lyme Borreliosis

Two patients in whom ocular Lyme disease was suspected and who had antibodies to Borrelia burgdorferi developed birdshot chorioretinopathy and carried the HLA-A29 antigen. In a series of 11 patients with birdshot chorioretinopathy who carried the HLA-A29 antigen, three patients had antibodies against B. burgdorferi as determined by either immunofluorescence assay, enzyme-linked immunosorbent assay, Western blot analysis, or a combination of these tests. Further studies will be necessary to evaluate whether this is a false-positive reaction or whether B. burgdorferi has a causative role in the pathogenesis of birdshot chorioretinopathy.

Determination of basal tear turnover in insulin-dependent diabetes mellitus patients by fluorophotometry

The tear turnover was determined by fluorophotometry in 25 insulin-dependent diabetes mellitus (IDDM) patients without retinopathy and 29 IDDM patients with (pre-)proliferative retinopathy. The results were compared with those in 34 healthy controls, to investigate the lacrimal gland function in diabetic patients. The tear turnover was calculated from the decay of the relative tear fluorescein concentration values measured after instillation of one μL of fluorescein.The tear turnover values in both patient groups did not correlate significantly with age or diabetes duration (linear correlation coefficients: r < 0.3). The tear turnover values in patients both without retinoplathy and with (pre-)proliferative retinopathy did not differ significantly from those in healthy controls (mean ± SD in %/min: 13.7 ± 4.5, 14.7 ± 5.8 and 15.5 ± 5.1, respectively; P > 0.16). The tear turnover was significantly decreased in eyes having a BUT shorter than 10 seconds compared with eyes having a BUT longer than 10 seconds (P < 0.05). The tear turnover values correlated significantly with the HbA1c and Schirmer-test values in patients with (pre-)proliferative retinopathy (r = 0.7 and r = 0.4, respectively; P < 0.02) and with the blood glucose values in patients without retinopathy (r = 0.41, P = 0.04).Since the tear turnover was not significantly decreased in IDDM patients in comparison with healthy controls the corneal disorders which are more frequently seen in these patients than in a healthy population may not be attributed to a decrease in tear production.