Thorsten R. Stolwijk

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 timolol with and without benzalkonium chloride: epithelial permeability and autofluorescence of the cornea in glaucoma

Epithelial permeability and autofluorescence of the cornea were determined by fluorophotometry in 21 patients with open-angle glaucoma or ocular hypertension using timolol medication with the preservative benzalkonium chloride (BAC) and 2 weeks after changing to timolol medication without BAC. The investigation was performed to determine whether removal of BAC would reduce toxic effects on the cornea and complaints of sensations of burning or dry eye. Corneal epithelial permeability decreased significantly after changing medication (mean decrease per patient 27%, P=0.025). Corneal autofluorescence increased significantly after changing medication suggesting an alteration in corneal metabolism (mean increase per patient 6%, P = 0.003). Timolol without BAC was found to be as effective as timolol with BAC in reducing intraocular pressure (P=0.4). Removal of BAC from timolol resulted in an improvement of corneal epithelial barrier function and in a reduction of complaints. The improvement was found to be proportional to the duration of the preceding BAC-containing therapy.

Analysis of tear fluid proteins in insulin-dependent diabetes mellitus

Abstract. Secretory immunoglobulin A, lactoferrin, lysozyme and tear specific pre‐albumin were analyzed in stimulated tear fluid of 25 diabetic patients without retinopathy and in 29 diabetic patients with (pre‐) proliferative retinopathy using high performance liquid chromatography. Results were compared to those obtained in 26 healthy controls to determine the effect of diabetes mellitus on the exocrine function of the main lacrimal gland. Sodium dodecyl sulfate polyacrylamide gel electrophoresis onto minigels was performed on 20 tear samples for verification of high performance liquid chromatography fractions recorded. The mean total protein values in tear fluid (Bradford assay) of diabetics without retinopathy, with retinopathy and healthy controls did not differ significantly (mean in mg/ml ± sd: 6.4 ± 2.2, 5.9 ± 2.0 and 5.7 ± 1.7, respectively; Mann‐Whitney: p>0.2). High performance liquid chromatography showed an increased secretory immunoglobulin A and decreased peak 5 OD280 (+56% and ‐38%, respectively; p< 0.02) in patients without retinopathy, whereas in patients with retinopathy lysozyme was increased (+27%; p< 0.01) and tear specific pre‐albumin and peak 5 OD280 decreased (‐24% and ‐42%, respectively; p< 0.04), when compared to healthy controls. These inconsistent differences do not uniformly suggest an exocrine dysfunction of the main lacrimal gland in diabetic patients.

Corneal autofluorescence in diabetic and penetrating keratoplasty patients as measured by fluorophotometry.

At first it was verified that the major part of the fluorophotometer signal obtained when measuring corneal autofluorescence originated from fluorescence and not from scatter of excitation light at the corneal surface. The minimum percentage of the signal which can be attributed to fluorescence was determined using a fluorescence blocking filter placed in the excitation and fluorescence light path, respectively. The minimum percentages in two healthy controls, two diabetic patients and two patients after penetrating keratoplasty ranged from 75% to 93% (mean 84%). Then the corneal autofluorescence was determined in 22 healthy controls, 18 non-insulin-dependent diabetes mellitus (NIDDM). 23 insulin-dependent diabetes mellitus (IDDM) and 21 penetrating keratoplasty patients in order to detect a possible difference in autofluorescence as a result of diabetes or penetrating keratoplasty. The means of the corneal peak autofluorescence values in the NIDDM, IDDM and penetrating keratoplasty patient groups were significantly higher than that in the healthy control group (mean values in ng equivalent fluorescin ml-1: 18.0 +/- 4.2 S.D., 20.6 +/- 5.1 S.D., 17.9 +/- 5.5 S.D. and 13.7 +/- 3.7 S.D., respectively; P less than 0.01). The mean values in the NIDDM and IDDM patients did not differ significantly (P = 0.09). The autofluorescence values were independent of age in all four groups (linear correlation coefficient: r less than 0.47). The corneal peak autofluorescence was linearly correlated with the diabetes duration in the NIDDM and IDDM patients [r = 0.6, P = 0.02; increase: 0.36 ng equiv. fluorescein ml-1 yr diabetes-1]. Our results show that corneal autofluorescence is an easily obtained parameter which can be of assistance in evaluating corneal metabolism.

Topical timolol, corneal epithelial permeability and autofluorescence in glaucoma by fluorophotometry

Corneal epithelial permeability and autofluorescence were measured by fluorophotometry in patients with open-angle glaucoma or ocular hypertension to quantify the epithelial function of the cornea and to evaluate its metabolic activity in 24 patients using daily timolol and 11 not using timolol. The findings were compared with those in age-matched healthy controls. Permeability values in patients using timolol were 1.9 times higher than in patients not using timolol and 2.5 times higher than in healthy controls (Mann-Whitney test P<0.001). Values for patients not using timolol did not differ from those for healthy controls (P=0.15). Corneal autofluorescence values in each patient group were higher than in healthy controls (P=0.002). Conclusions: (1) open-angle glaucoma or ocular hypertension alone does not affect corneal epithelial permeability; (2) daily instillation of timolol causes impairment of the corneal epithelial barrier; (3) open-angle glaucoma or ocular hypertension are likely to induce an increase of corneal autofluorescence.

Endogenous Fluorescence of Ocular Malignant Melanomas

The endogenous fluorescence of human choroid, sclera, and retinal pigment epithelium (RPE) in normal tissue and tissue with uveal melanoma was studied in vitro by a non-invasive and non-destructive fluorescence technique which had previously been applied for the diagnostic evaluation of pigmented lesions of the skin. The fluorescence of the normal choroid is rather dark, the normal sclera exhibits blue fluorescence and the RPE bright yellow fluorescence due to deposits of lipofuscin. In choroidal melanoma, the lipofuscin granulae at the level of the retinal pigment epithelium are cleaved off above the tumour and broken up into small remnants. The fluorescence intensity emitted from the tumour is rather low which agrees with previous findings on skin melanomas. The results may become interesting for diagnostic evaluation of uveal melanomas, uveal naevi, and pigmented conjunctival tumours by endogenous fluorescence.

Epithelial permeability in corneal grafts by fluorophotometry

AbstractThe epithelial permeability to fluorescein of 27 clear corneal grafts in 23 patients was determined by fluorophotometry at > 1 year after penetrating keratoplasty (PKP) so as to study the recovery of corneal epithelial function. The mean epithelial permeability of the corneal grafts did not differ significantly from that of normal corneas (0.042 ± 0.016 and 0.038 ± 0.017 nm/s, respectively; P>0.3). Multiple linear regression analysis showed that permeability correlated with recipient age but not with donor age (permeability increase, 0.00054 nm/s per year; r=0.6, P<0.005 and r=0.1, P>0.5, respectively). These results indicate that corneal grafts can regain a normal epithelial barrier function and that recovery of epithelial function is better in young than in old recipients. Offprint requests to: J.A. van Best

Corneal endothelial permeability and aqueous humor dynamics in normal pressure glaucoma

Corneal endothelial permeability and aqueous humor dynamics were studied in 17 non-treated normal pressure glaucoma patients in order to analyse the relevance of these parameters in the pathophysiology of this disease. Corneal endothelial permeability and aqueous humor flow were measured by fluorophotometry and aqueous outflow facility was determined by tonography. The results were compared with those of 17 healthy controls of similar age. The mean corneal endothelial permeability values and the aqueous flow and outflow facility values of the patients did not differ significantly from those of the healthy controls (P=0.8, P=0.2 and P=0.5, respectively). Normal pressure glaucoma does not affect the corneal endothelial permeability. The aqueous humor dynamics are not primarily involved in the pathophysiology of normal pressure glaucoma.