[Skip to Content]
[Skip to Content Landing]
September 1984

Corneal Nerve Alterations in Diabetes Mellitus

Author Affiliations

From the Cornea Research Laboratory, Department of Ophthalmology (Drs Ishida, Rao, del Cerro, and Aquavella) and the Center for Brain Research (Drs Ishida, Rao, and del Cerro), University of Rochester (NY) School of Medicine and Dentistry.

Arch Ophthalmol. 1984;102(9):1380-1384. doi:10.1001/archopht.1984.01040031122038

• The morphologic status of corneal innervation was studied in rats with streptozocin-induced diabetes. Animals were killed at 1, 4, 16, and 36 weeks. Corneal innervation was studied by light and electron microscopy using nonspecific cholinesterase reaction, gold chloride impregnation, and plastic-embedded sections. Increased irregularity in the periodicity of nerve fiber beading was observed in diabetic corneas with gold impregnation. Ultrastructural evidence of irregularities in the basal lamina of Schwann cells was demonstrated in 16- and 36-week-old diabetic animals, along with occasional axonal degeneration. These alterations constitute a constellation of early pathologic manifestations in the innervation of diabetic cornea. To our knowledge, this study represents the first demonstration of neural changes in diabetic corneas as well as nerve fiber changes in an avascular tissue in diabetes.

Schultz RO, van Horn DL, Perters MA, et al:  Diabetic keratopathy . Trans Am Ophthalmol Soc 1981;79:180-199.
Kenyon KR, Stark WJ, Stone DL:  Corneal endothelial degeneration and fibrous proliferation after pars plana vitrectomy . Am J Ophthalmol 1976;81:486-490.
Foulks GN, Thoft RA, Perry HD, et al:  Factors related to corneal epithelial complications after closed vitrectomy in diabetes . Arch Ophthalmol 1979;97:1076-1078.Article
Fukushi S, Merola LO, Kinoshita JH:  Corneal re-epithelialization in the diabetic rats . Invest Ophthalmol Vis Sci 1979;18:73.
Quaranta CA:  Sulla freguenza di una particolare forma di alterazione corneale in diabetici . Acta Biomed Ateneo Parmense 1954;25:548-555.
Scullica L, Proto F:  Rilievi clinici e stastistici sulla sensibilita corneale nei diabetici . Boll Ocul 1965;44:944-954.
Schwartz DE:  Corneal sensitivity in diabetics . Arch Ophthalmol 1974;91:174-178.Article
Rogell GD:  Corneal hypesthesia and retinopathy in diabetes mellitus . Ophthalmology 1980;87:229-233.Article
Riss B, Binder S:  Die Hornhautsensibilitat nach lichtkoagulation bei diabetischer Retinopathie . Grafes Arch Clin Exp Ophthalmol 1981; 217:143-147.Article
MacRae SM, Engerman RL, van Horn DL, et al:  Is decreased corneal sensitivity related to control and duration of diabetes mellitus? Invest Ophthalmol Vis Sci 1982;22( (suppl) ):200.
Hyndiuk RA, Kazarian EL, Schultz RO, et al:  Neurotrophic corneal ulcers in diabetes mellitus . Arch Ophthalmol 1977;95:2193-2196.Article
Henkind P, Wise GN:  Descemet's wrinkles in diabetes . Am J Ophthalmol 1961;52:371-374.
Kenyon K, Wafai Z, Michels R, et al:  Corneal basement membrane abnormalities in diabetes mellitus . Invest Ophthalmol Vis Sci 1978; 17( (suppl) ):245.
Hatchell DL, Magolan JJ, Besson MJ, et al:  Damage to the epithelial basement membrane in the corneas of diabetic rabbits . Arch Ophthalmol 1983;101:469-471.Article
Ishii Y, Lahav M, Mukai Y:  Corneal changes in diabetic patients and streptozotocin diabetic rats: An ultrastructural correlation . Invest Ophthalmol Vis Sci 1981;21( (suppl) ):154.
Karnovsky MJ, Root L:  A 'direct-coloring' thiocholine method for cholinesterases . J Histochem Cytochem 1964;12:219-221.Article
Koelle GB, Friedenwald JS:  A histochemical method for localizing cholinesterase activity . Proc Soc Exp Biol Med 1949;70:617-622.Article
Ishida N, del Cerro M, Rao GN, et al:  Corneal stromal innervation: A qualitative analysis of distribution . Ophthalmic Res 1984;16:139-144.Article
Del Cerro M, Standler NS, del Cerro C:  High resolution optical microscopy of animal tissue by the use of submicrometer thick sections and a new stain . Microsc Acta 1980;83:217-220.
Del Cerro M, Cogen J, del Cerro C:  Stevenel's blue, an excellent stain for optical microscopical study of plastic embedded tissues . Microsc Acta 1980;83:117-121.
Peters MA, Schultz RO, Klewin KM, et al:  Diabetic keratopathy and peripheral sensation . Invest Ophthalmol Vis Sci 1982;22( (suppl) ):200.
Fagerberg SE:  Diabetic neuropathy: A clinical and histological study on the significance of vascular affections . Acta Med Scand 1959; (suppl) 345:1-81.
Raff MC, Sangalang V, Asbury AK:  Ischemic mononeuropathy multiplex associated with diabetes mellitus . Arch Neurol 1968;18:487-499.Article
Thomas PK, Eliasson SG:  Diabetic neuropathy , in Dyck PJ, Thomas PK, Lambert EH (eds): Peripheral Neuropathy . Philadelphia, WB Saunders Co, 1975, vol 2, pp 956-981.
Brown MJ, Martin JR, Asbury AK:  Painful diabetic neuropathy: A morphometric study . Arch Neurol 1976;33:164-171.Article
Bischoff A:  Die Diabetische Neuropathie . Praxis 1965;14:723-729.
Bischoff A:  Diabetic neuropathy: Morbid anatomy, pathophysiology and pathogenesis based on electron-microscopic findings . Germ Med Methods 1968;13:214-218.
Behse F, Buchthal F, Carlsen F:  Nerve biopsy and conduction studies in diabetic neuropathy . J Neurosurg Psychiatry 1977;40:1072-1084.Article
Martin MM:  Diabetic neuropathy: A clinical study of 150 cases . Brain 1953;76:594-624.Article
Jakobsen J:  Axonal dwindling in early experimental diabetes: II. A study of isolated nerve fibers . Diabetologica 1976;12:547-553.Article
Sima AAF, Robertson DM:  Peripheral neuropathy in the diabetic mutant mouse: An ultrastructural study . Lab Invest 1979;40:627-632.
Sima AAF, Bouchier M, Christensen H:  Axonal atrophy in sensory nerves of the diabetic BB-Wistar rat: A possible early correlate of human diabetic neuropathy . Ann Neurol 1982; 13:264-272.Article
Chopra JS, Hurwitz LJ, Montogomery DAD:  The pathogenesis of sural nerve changes in diabetes mellitus . Brain 1969;92:391-418.Article
Schlaepfer WW, Gerritsen GC, Dulin WE:  Segmental demyelination in the distal peripheral nerves of chronically diabetic Chinese hamsters . Diabetologica 1974;10:541-548.Article
Rodger FC:  The pattern of the corneal innervation in rabbits . Br J Ophthalmol 1950; 34:107-113.Article
Rodger FC:  The significance of beading in corneal nerve fibers . J Physiol 1951;115:67.
Felten DL, Felten SY, Melman A:  Noradrenergic innervation of the penis in control and streptozotocin-diabetic rats: Evidence of autonomic neuropathy . Anat Rec 1983;206:49-59.Article