Tear Film and Ocular Surface Changes in a Rabbit Model of Neurotrophic Keratitis JEFFREY P. GILBARD, MD, 1•2 SCOTT R. ROSSI, MS1
Abstract: The authors studied the tear film and ocular surface in a rabbit model of neurotrophic keratitis to determine the extent to which the surface disease of neurotrophic keratitis resembled keratoconjunctivitis sicca. After denervation, tear film osmolarity increased and remained significantly elevated for 14 weeks. The ocular surface developed decreased conjunctival goblet cell density, decreased corneal epithelial glycogen, and morphologic changes similar to those seen in keratoconjunctivitis sicca. Although the conjunctival changes were consistent with the increases in tear film osmolarity and the surface disease of keratoconjunctivitis sicca, the corneal changes observed with denervation, including slit-lamp findings, morphologic changes, and decreases in glycogen, were too severe and rapid in onset to be accounted for by osmolarity alone. Neurotrophic "keratitis" is an ocular surface disease composed in part of the surface disease of keratoconjunctivitis sicca. However, the data also support an additional mechanism for corneal disease that could be due to the trophic influence of the trigeminal nerve. Ophthalmology 1990; 97:308-312
The etiology of the ocular surface disease in neurotrophic keratitis is unclear, and many hypotheses have been proposed to explain the changes. Two hypotheses that have endured for over 100 years 1 are now the most prominent: ( 1) the keratitis can be attributed to ocular surface drying and (2) the keratitis can be attributed to the trophic influence of the trigeminal nerve. Some evidence exists that ocular surface drying plays an important role in neurotrophic keratitis. In a rat model of neurotrophic keratitis, areas of the cornea normally covered by the lids were found to be normal in appearance, 2 and clinically the therapeutic value of tarsorrhaphy is well known. 3 Furthermore, when topical proparacaine is used to decrease ocular surface sensation, tear secretion decreases 60 to 75%. 4 More recently, we demonstrated that this decrease in tear secretion can increase tear film Originally received: August 24, 1989. Revision accepted: November 25, 1989. 1
2
Cornea Unit, Eye Research Institute, Boston. Department of Ophthalmology, Harvard Medical School, Boston.
Supported in part by grant EY03373 from the National Institutes of Health. Reprint requests to Jeffrey P. Gilbard, MD, Eye Research Institute, 20 Staniford St, Boston, MA 02114.
308
osmolarity in rabbits and humans in the presence of normallacrimal gland tissue. 5 The evidence that ocular surface drying plays a role in neurotrophic keratitis does not exclude a trophic influence of the trigeminal nerve. It has been proposed that the trophic influence may occur via axonally transported substances such as proteins. 6 There is evidence for such a mechanism regarding the trophic effect of nerve on skeletal muscle. 7 In the eye, results indicate that decreases in corneal mitosis and corneal thinning are not reversed by lid closure. 4 •8 However, it is evident that lid closure decreases evaporation but does not reverse the decrease in tear secretion. We studied the tear film and ocular surface in a previously described rabbit model of neurotrophic keratitis6 •9 to determine the extent to which the surface disease of neurotrophic keratitis resembled that of keratoconjunctivitis sicca.
MATERIALS AND METHODS SURGICAL PROCEDURE
Eight New Zealand white rabbits of both sexes and weighing approximately 2.0 kg were anesthetized with
GILBARD AND ROSSI
330 ~ LlJ
•
- - Operated eyes --o- Contralatera~ control eyes P
Abstract: The authors studied the tear film and ocular surface in a rabbit model of neurotrophic keratitis to determine the extent to which the surface disease of neurotrophic keratitis resembled keratoconjunctivitis sicca. After denervation, tear film osmolarity increased and remained significantly elevated for 14 weeks. The ocular surface developed decreased conjunctival goblet cell density, decreased corneal epithelial glycogen, and morphologic changes similar to those seen in keratoconjunctivitis sicca. Although the conjunctival changes were consistent with the increases in tear film osmolarity and the surface disease of keratoconjunctivitis sicca, the corneal changes observed with denervation, including slit-lamp findings, morphologic changes, and decreases in glycogen, were too severe and rapid in onset to be accounted for by osmolarity alone. Neurotrophic "keratitis" is an ocular surface disease composed in part of the surface disease of keratoconjunctivitis sicca. However, the data also support an additional mechanism for corneal disease that could be due to the trophic influence of the trigeminal nerve. Ophthalmology 1990; 97:308-312
The etiology of the ocular surface disease in neurotrophic keratitis is unclear, and many hypotheses have been proposed to explain the changes. Two hypotheses that have endured for over 100 years 1 are now the most prominent: ( 1) the keratitis can be attributed to ocular surface drying and (2) the keratitis can be attributed to the trophic influence of the trigeminal nerve. Some evidence exists that ocular surface drying plays an important role in neurotrophic keratitis. In a rat model of neurotrophic keratitis, areas of the cornea normally covered by the lids were found to be normal in appearance, 2 and clinically the therapeutic value of tarsorrhaphy is well known. 3 Furthermore, when topical proparacaine is used to decrease ocular surface sensation, tear secretion decreases 60 to 75%. 4 More recently, we demonstrated that this decrease in tear secretion can increase tear film Originally received: August 24, 1989. Revision accepted: November 25, 1989. 1
2
Cornea Unit, Eye Research Institute, Boston. Department of Ophthalmology, Harvard Medical School, Boston.
Supported in part by grant EY03373 from the National Institutes of Health. Reprint requests to Jeffrey P. Gilbard, MD, Eye Research Institute, 20 Staniford St, Boston, MA 02114.
308
osmolarity in rabbits and humans in the presence of normallacrimal gland tissue. 5 The evidence that ocular surface drying plays a role in neurotrophic keratitis does not exclude a trophic influence of the trigeminal nerve. It has been proposed that the trophic influence may occur via axonally transported substances such as proteins. 6 There is evidence for such a mechanism regarding the trophic effect of nerve on skeletal muscle. 7 In the eye, results indicate that decreases in corneal mitosis and corneal thinning are not reversed by lid closure. 4 •8 However, it is evident that lid closure decreases evaporation but does not reverse the decrease in tear secretion. We studied the tear film and ocular surface in a previously described rabbit model of neurotrophic keratitis6 •9 to determine the extent to which the surface disease of neurotrophic keratitis resembled that of keratoconjunctivitis sicca.
MATERIALS AND METHODS SURGICAL PROCEDURE
Eight New Zealand white rabbits of both sexes and weighing approximately 2.0 kg were anesthetized with
GILBARD AND ROSSI
330 ~ LlJ
•
- - Operated eyes --o- Contralatera~ control eyes P
