The healing effect of all-trans retinoic acid on epithelial corneal abrasions in rabbits.

PURPOSE: The aim of the study was to investigate the possible healing effect of the vitamin A analogue all-trans retinoic acid 0.05% (RA) in vaseline on epithelial corneal abrasions in 13 ocularly healthy Copenhagen white rabbits. METHODS: A corneal abrasion with a diameter of 6 mm was created centrally in both eyes with a trephine and subsequent rubbing off of the corneal epithelium with an n-heptanol soaked swab The corneal abrasions were treated twice daily with topical applications (50 microl); RA was placed in the right inferior fornix and its vaseline vehicle in the left inferior fornix. Photographic documentation of fluorescein stained, non-healed areas, was performed at time points 0, 12, 24, 36, 48 and 72 h. The rabbits were sacrificed by an overdose of pentobarbital and enucleated. Planimetry was performed from corneal photographs. RESULTS: Healed epithelial mean area at time point 36 h was significantly higher after RA compared to vehicle (p=0.036, paired t-test). Median time to 75% and 85% healing was significantly shorter for RA compared to vehicle (p= 0.03 and 0.02, log rank-test). No morphological difference, evaluated by light microscopy (hematoxylin-eosin) or scanning electron microscopy, was noted between the two treatments. CONCLUSION: It is concluded that RA 0.05% applied twice daily increases the healing rate compared to vaseline vehicle.

Viscous carbomer eye drops in patients with dry eyes. Efficacy and safety. A randomized, open, cross-over, multicentre study.

The efficacy and safety of a new carbomer containing ocular gel was compared to a commonly used 1.4% polyvinyl alcohol-based (PVA) offificial tear preparation. Sixty-one patients with symptoms and signs of dry eyes were treated with each preparation separately for two weeks in a multicentre, randomized, open cross-over study. A statistically significant difference in favour of the new viscous carbomer eye drops compared to the PVA preparation was achieved in reducing the symptom of 'dryness', the total symptom score and in prolonging the break-up time. During the carbomer eye drops period the mean daily frequency of application was 3.92 compared to 4.64 for the PVA eye drops period (p = 0.02). Twenty-three patients (38%) reported adverse events only while using the carbomer gel and 5 (8%) only while using the PVA eye drops (p < 0.001). 'Blurred vision' was the most common adverse event reported. The present carbomer containing ocular gel may offer advantages in the treatment of dry eyes.

A bioavailability comparison in rabbits after a single topical ocular application of prednisolone acetate formulated as a high-viscosity gel and as an aqueous suspension.

To increase contact time between drug and ocular surface and thus improve the bioavailability, we used the high-viscous, water-soluble polymer carbomer Leogel (carbomer 0.5%). The drugs were applied to Copenhagen white rabbits as a single application. We compared the bioavailability of prednisolone acetate 0.5% in Leogel with fusidic acid 1% after 1, 4, 7 and 10 h (n = 3 at each time points) with that obtained when doubling the prednisolone acetate concentration in unchanged Leogel and fusidic acid 1% in 12 rabbits. In addition we compared the bioavailability of prednisolone acetate 0.5% given in 1) Leogel using fusidic acid 1% with that obtained using 2) aqueous sulfacetamide sodium 10% as vehicle after 0.5, 1, 1.5, 2, 3, 6, 8 and 12 h (n = 6 at each time points) in 54 rabbits. When doubling the prednisolone acetate dose an increase in bioavailability was achieved in conjunctiva, cornea and aqueous humour with 1.57, 3.86 and 2.18 times, respectively. Prednisolone concentrations in cornea, conjunctiva and aqueous humour were higher using the Leogel vehicle than using the aqueous suspension. The bioavailability in 0-12 h for prednisolone acetate in Leogel and fusidic acid 1% to conjunctiva was significantly higher (p = 0.003) than for prednisolone acetate in aqueous and sulfacetamide sodium 10%. The bioavailability (0-6 h) for conjunctiva was significantly higher for the Leogel preparation than for the aqueous suspension (p < 0.001). For cornea and aqueous humour, the bioavailability values for the total period (0-12 h) do not differ significantly. However, for the first 6 h the difference is significant (p < 0.001 for cornea and p = 0.003 for aqueous humour).

An ocular bioavailability comparison in rabbits of prednisolone acetate after repeated topical applications formulated as a high-viscosity gel and as an aqueous suspension.

To increase contact time between drug and ocular surface and thus improve the ocular bioavailability, we used the high-viscous, water-soluble polymer carbomer Leogel (carbomer 0.5%). We compared the bioavailability of prednisolone acetate 0.5% given in 1) Leogel using fusidic acid 1% with that obtained using 2) aqueous sulfacetamide sodium 10% as vehicle. We applied the drugs to Copenhagen white rabbits as repeated topical applications (gel preparation: twice daily; aqueous preparation: four times daily) for one week. Dosis regimen was chosen according to earlier investigations (Johansen et al. 1995). Prednisolone concentrations in cornea, conjunctiva and aqueous humour were shown to be higher using the Leogel vehicle than using the aqueous suspension. Fusidic acid and sulfacetamide sodium values were compared with values from a single application (Johansen et al. 1995). Fusidic acid reached higher concentration levels in cornea, conjunctiva and aqueous humour after repeated applications than after a single application. Sulfacetamide sodium concentrations did not rise when applied four times daily for one week. Leogel increases the ocular bioavailability of substance(s) in the gel and allows lower drug concentrations and/or application frequencies.

Lubrithal (Leo viscous eye gel), precorneal residence time in normal and dry eyes.

In an open, right/left controlled study we compared the effects of topical carbomer gel Lubrithal (Leo viscous eye gel) and polyvinyl alcohol (Liquifilm, Allergan) in 20 patients with dry eyes and in 20 healthy subjects. The average precorneal residence time of carbomer gel in patients and healthy subjects was 92.8 min (+/- 35.7) and 36.5 min (+/- 14.2), respectively, while it was 40.8 min (+/- 19.4) and 19.5 min (+/- 8.3) in the polyvinyl alcohol group. The tear break up time was 10 min after instillation significantly longer with the carbomer gel: 23.0 seconds (+/- 5.5) in dry eye patients and 26.2 seconds (+/- 4.4) in healthy subjects compared to polyvinyl alcohol: 10.4 seconds (+/- 3.4) in dry eye patients and 16.5 seconds (+/- 7.1) in healthy subjects (p < 0.001). Seventy-five per cent of the dry eye patients preferred Lubrithal.

Lactose malabsorption and tolerance of lactose-hydrolyzed milk. A double-blind controlled crossover study.

Eleven lactose-intolerant patients were investigated in a double-blind crossover controlled study. In random sequence they received 500 ml of either ordinary cow milk (lactose content, 25 g) or the same amount of low-lactose milk (85% of the lactose hydrolyzed), which had been processed by Lactozym 3000 L for 24 h at 4 degrees C. A significantly increased blood glucose rise from fasting levels was demonstrated in the low-lactose tests. Similarly, a significant reduction of liquid stool frequency, abdominal colics, distention, borborrhygmia, and flatulence was demonstrated. It was concluded that further studies, including long-term treatment of lactose-intolerant children, are indicated.