Br J Ophthalmol: first published as 10.1136/bjo.66.11.705 on 1 November 1982. Downloaded from
British Journal of Ophthalmology, 1982, 66, 705-708
Corticosteroids and corneal epithelial wound healing
G. PETROUTSOS, R. GUIMARAES, J. P. GIRAUD AND Y. POULIQUEN From the Centre de Recherche d'Ophtalmologie, INSERM U 86, H6tel-Dieu, Place du Parvis Notre-Dame, 75181 Paris Cedex 04, France
SUMMARY The effect of corticosteroids on the re-epithelialisation of corneas from which the epithelium was removed has been determined by fluorescein staining, photography, and light microscopy. Our results suggest that hydroxymethyl progesterone 1 05% (p<005), prednisolone 1-0% (p<0-001), and dexamethasone 0-1% (p<0001) administered 6 times a day retard the epithelial wound healing compared with control animals which received isotonic NaCl.
The effect of corticosteroids on the comeal epithelium The method described by Moses et al. " was used is important for a number of reasons. Corticosteroids for removal of the corneal epithelium. Our tube has are the most effective drugs for the nonspecific sup- an internal diameter of 7-3 mm at the tip. pression of inflammation.' They prevent corneal neo- Rabbits were anaesthetised with sodium pentobar- vascularisation in clinical and experimental work23 bital administered in a marginal ear vein (25 mg per and are widely used in current ophthalmology. Finally kg body weight). Two drops of Novesine (oxybypro- the integrity4 and healthy quality' of the corneal caine hydrochlorate 0 4%) were instilled into each epithelium are essential to the health of the cornea. eye. Each eye was then gently proptosed, and the lip Anti-inflammatory steroids may delay the healing of of the iodine tube was wiped on a filter paper and held corneal stromal wounds,67 produce glaucoma,8 and against the cornea for 3-5 minutes. Recording of the increase the liability to infection.9 10 lesion was by photography. The cornea was stained This paper reports experimental results of the with one drop of 0-5% fluorescein (without preserva- effects of different corticosteroids on the healing of tives) and then washed with 2 drops of isotonic NaCl http://bjo.bmj.com/ rabbit corneal epithelium. solution. The lesions were photographed on Kodak Tri-X film 4 times a day until the complete healing of Material and methods the corneal epithelial wound, which was determined by the absence of corneal fluorescein uptake. An Experimental animals. Twenty pigmented rabbits of annular electronic flash covered with a Wratten 47 B both sexes weighing 2 to 3 kg each were used in this filter was fixed round the objective of a slit-lamp, and study. Each animal was examined in a slit-lamp micro- the objective was covered with a Wratten 12 filter to on October 2, 2021 by guest. Protected copyright. scope and no evident pathological findingswere noted obtain a good contrast on black-and-white films. prior to the experiment. With a Quantimet 720 (Cambridge Instruments, Epithelial healing study. Forty eyes were divided in UK) the fluorescein-stained areas were measured and 4 groups of 10: Group A received topical isotonic converted to square millimeters. NaCl solution used as control; group B received top- For each eye a healing curve was obtained by plot- ical commercial hydroxymethyl progesterone 1 05% ting successive areas of the wound against time. The solution (Medrysone); group C received topical com- best fitting curve by the least squares method was mercial prednisolone sodium phosphate 1 -0% solu- obtained by means of a linear regression. tion (Solucort); group D received topical commercial The diameter of the first corneal wound for each dexamethasone sodium phosphate 0-1% solution eye was also measured at 6 hours. (Decadron phosphate). All these drugs were given 6 Histological study. Four days after treatment 4 eyes times a day. from each group were enucleated, stained with haematoxylin and eosin, and prepared for histological Correspondence to Dr G. Petroutsos, Laboratoire d'Ophtalmologie, examination. Hotel-Dieu, Place du Parvis Notre-Dame. 75181 Paris Cedex 04. Under the microscope we counted the total number France, INSERM U 86. of cellular nuclei on the 4 specimens on a 0-35 mm 705 Br J Ophthalmol: first published as 10.1136/bjo.66.11.705 on 1 November 1982. Downloaded from
706 G. Petroutsos, R. Guimaraes, J. P. Giraud, and Y. Pouliquen
lA http://bjo.bmj.com/
Figs. IA, B, C, D Histological cross-sections ofhealed epithelium after 4 days of treatmnent. (x622). A: Top left, control cornea. B: Top right, cornea treated by hydroxymethyl progesterone. C: Left cornea treated by prednisolone O-I %. D: Right cornea treated by dexamethasone I 0O%. Note the difference appearing: in the cellular aspect; in the numberoflayers; in the cellular nuclei.
length of object. Six different levels of the same p
Corticosteroids and corneal epithelial wound healing 707
Table 2 Rate ofdecrease ofarea ofepithelial wound Our results suggest that topical application of (mm2/h) prednisolone 1 -0% and dexamethasone 01% 6 times a day decreases (p<0001) the epithelial healing rates Group A Group B Group C Group D Control Hydroxymethyl Prednisolone Dexamethasone in comparison with those of the control group. progesterone 10%I 0.1% Hydroxymethyl progesterone also produces a slight 1-05% (p<005) retardation in the epithelial wound healing. There is a statistically significant difference at the 1-25 106 074 0(48 1-07 1*11 060 074 0-001 level between the mean healing rates of group 115 1-08 053 052 B (hydroxymethyl progesterone) and groups C 1*14 105 0-82 053 (prednisolone) and D (dexamethasone). 132 0-98 061 048 are confirmed the study. 1 08 085 054 0-42 Our results by histological 1-13 115 053 054 The total number of cellular nuclei was reduced 1-02 1-05 0-81 0-61 (p
There were only a few foci where the upper epithelial that 1-0% prednisolone acetate and 0-% dexameth- http://bjo.bmj.com/ layers consisted of flattened parakeratotic cells (Fig. asone did not affect the course of re-epithelialisation IB). after partial corneal epithelial denudation. On the In contrast, the epithelium of groups C and D was contrary the healing rate was significantly retarded one or 2 layers thick. The cells of the basal layer after complete corneal denudation. We think that the seemed to have lost their junctional units, and the larger diameter of the epithelial denudation used in superficial layers were formed of extremely flattened our method explains the different results obtained.
cells with hyperchromatic nuclei (Figs. 1C, D). The Moreover in this study the drugs were administered 3 on October 2, 2021 by guest. Protected copyright. histological study was restricted to the centre of the times daily. lesion. Epithelial punctate keratitis has also been reported in human corneas after topical application of Discussion prednisolone'7 and important morphological changes in the epithelium of rabbit cornea. 8 It has been shown There are certain conditions in which, despite a break that repeated application of prednisolone 1 00% and in the corneal epithelium, we are obliged to administer dexamethasone 0-1% can retard the epithelial wound topical corticosteroids. In order to obtain information healing of a superficial epithelium ulcer. on the epithelial regeneration of the cornea when For hydroxymethyl progesterone, a synthetic corti- treated with different corticosteroids the healing pro- costeroid which is an effective anti-inflammatory agent cess of a superficial epithelial corneal ulcer was mea- for certain external conditions'9 free from the pro- sured. Histological studies have been performed to pensity to raise the intraocular pressure,20 the results evaluate the quality of the regenerated epithelium. in our model proved that the epithelial wound healing For the removal of the corneal epithelium we used a was slightly retarded. The purpose of this study was to reproducible method" which respects'2 the epithelial facilitate recognition of the adverse effect of the corti- basal membrane. costeroids and to stress the need for further investiga- Br J Ophthalmol: first published as 10.1136/bjo.66.11.705 on 1 November 1982. Downloaded from
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