Richard A. Thoft

Corneal Epithelial Changes in Diabetic Rats

Electron microscopy of streptozotocin diabetic rat eyes showed increased intracellular levels of tonofilaments and glycogen, thickenings and infoldings of subepithelial basement membrane and basal cell degeneration after 8 months. Glycogen, glucose, sorbitol, and fructose were measured in corneal epithelium from short- and long-term diabetic rats. The small increase in sorbitol pathway products which were found after 8 months of diabetes (less than 1.0 mosm/1 tissue water) confirmed similar findings in rabbits and humans. Thus, the morphologic changes occur in the absence of significant accumulation of sorbitol pathway products. Osmotic damage secondary to corneal epithelial cell accumulation of sorbitol is probably not a significant factor in corneal epithelial diabetic disease.

Indications for Conjunctival Transplantation

Long-term follow-up (two to five years) of 12 unilateral chemical burn patients treated by conjunctival transplantation shows permanent stabilization of the ocular surface. The procedure was used in another group of five patients with unilateral recalcitrant epithelial defects. Regardless of the etiology of the epithelial defect, prompt healing of the surface occurs after conjunctival transplantation with no further stromal loss and long-term stabilization of the surface. Such results suggest that epithelial replacement may be a valuable therapeutic approach to a variety of ocular surface disorders.

Ocular Cicatricial Pemphigoid Associated with Hyperproliferation of the Conjunctival Epithelium

We determined the mitotic rate, measured by evaluating uptake of tritiated thymidine autoradiographically, and the frequency of goblet cells in conjunctival epithelial biopsy specimens from nine normal subjects and from 11 patients (seven women and four men ranging in age from 50 to 80 years) with ocular cicatricial pemphigoid. The mitotic rate of patients with the disease was significantly higher than that of normal subjects, 7.2 +/- 2.2 vs 1.6 +/- 0.2 labeled cells per 100 basal epithelial cells (P less than .01). The goblet cell frequency, however, was significantly less in patients than in normal subjects. This suggests that ocular cicatricial pemphigoid is associated with hyperproliferation of the conjunctival epithelium, with a concurrent failure of normal conjunctival differentiation.

Similar Epithelial Healing Rates of the Corneas of Diabetic and Nondiabetic Patients

We developed a reliable method for measuring corneal regeneration in humans with noninvasive, readily available photographic techniques. We then used this method prospectively to compare the rates of primary corneal regeneration after surgery in a series of 27 diabetic and nondiabetic patients. The rates of corneal epithelial regeneration were not significantly different when diabetic patients were compared with nondiabetic patients. A tendency toward recurrent epithelial defects was confirmed in the diabetic patients, however.

The extracellular space of the lens

The extracellular space of rat, rabbit and calf lenses has been estimated in vitro using radioactive non-metabolized carbohydrates and 24Na as test substances. The size of the extracellular space ranges from 4 to 13% of the lens water, depending on the test substance used. In addition, the extracellular space of the lens in situ was estimated from chemical determination of the sodium content of aqueous humor and of the lens. This sodium space, presumably the maximal size of the extracellular space, is from 10 to 13% of the lens water, depending upon the animal studied. The sucrose space of the rat lens was found in vivo to be about 5%.

Permeability of regenerated corneal epithelium

The penetration of non-metabolized 14carbon labelled α-amino-isobutyric acid (α-AIB), 3-o-methyl glucose, and d-mannitol across the regenerated corneal epithelium in rabbits has been determined in vivo and compared to penetration into bare stroma and across normal epithelium. From these values it was possible to calculate the permeability of the epithelium to these analogues of nutrient compounds. An estimate of endothelial permeability to these compounds was made after measuring penetration across the endothelium from stroma into aqueous humor. The data confirm the relative impermeability of the epithelial layer and it is noted that re-establishment of epithelial integrity, as measured by fluorescein staining, is coincident with resumption of impermeability to the small molecules. The results indicate that attempts to nourish epithelium from the tear surface require concentrations and contact times which are best achieved by constant infusion techniques. Endothelial permeabilities were much greater than epithelial permeabilities and these nutrient molecule analogues apparently penetrate slightly more rapidly than does sodium.