Recurrent herpetic keratitis in mice]

In order to investigate the mechanism of recurrence in herpes simplex keratitis, it is very important to establish an animal model. As a first step, mice were examined with the slit-lamp biomicroscope to determine whether they spontaneously showed recurrent epithelial keratitis after healing of primary herpetic keratitis. Among 90 eyes of 45 inbred C57BL/6 mice, recurrent epithelial keratitis stained with fluorescein was observed in 10 eyes of 9 mice during the observation period up to 50 days after the primary corneal infection with herpes simplex virus (HSV) type I Amakata strain (virulent strain). Recurrent epithelial keratitis was observed in 17 eyes of 15 mice among 116 eyes of 58 ddy mice infected with HSV-I Ska strain (avirulent strain). The epithelial lesions showed punctate or dendritic patterns and continued for one to 7 days. HSV antigen was detected by the fluorescent antibody technique in the cornea of 5 out of 8 eyes which showed recurrent epithelial keratitis using another ddy mice group tested. It was limited in the epithelium of the cornea. These results show that mice herpetic keratitis recurs spontaneously.     

Corneal sensitivity and substance P in experimental herpes simplex keratitis in mice

Experimental herpes simplex keratitis in the mouse produced a rapid fall in both corneal sensitivity and levels of corneal substance P (SP). This finding supports the association of SP with sensory neurones and shows that such levels can be used as an indication of damage to neurones resulting, for example, from infection with HSV. However, the delay in recovery of SP compared to the more rapid and complete recovery of sensitivity suggests that SP in the cornea is not directly involved in mediation of the blink reflex.     

Sequential antibody changes following ulcerative herpetic keratitis.

Blood and tear levels of immunoglobulins against herpes simplex virus (HSV) were examined in 28 patients with dendritic keratitis over a period of 28 days. By means of an indirect micro-immunofluorescent technique blood and tear HSV IgG were detected, but neither circulating HSV IgM nor local HSV IgA were found. Over a four-week interval non-diagnostic fluctuations of HSV IgG occurred in most patients, though seven (25%) developed a rising blood IgG titre. Tear IgG appeared to be an exudate from blood. HSV was isolated from 68% of corneal swabbings and 11% of conjunctival swabbings. This study provides guidelines for laboratory testing in recurrent herpetic keratitis.     

The pathogenesis of herpetic keratitis

BACKGROUND: Viral infections of Herpes origin are the most commonly encountered ones in man. The most important member of this family is the Herpes simplex virus (HSV), two varieties of which are known to exist: HSV-1 affects predominantly the upper half of the body, whereas HSV-2 is associated mainly with diseases of the urogenital tract. In the immunocompetent host, viral replication is usually confined to cutaneous and mucocutaneous sites, invasion of subcutaneous tissues being impeded by an early onset of non-specific defence mechanisms. These are rapidly complemented by the specific, mainly cellular, immune response. PATIENTS: Epithelial dendritic keratitis is the first symptomatic clinical finding, and after several recurrences, the corneal stroma may become involved. This condition of herpetic stromal keratitis (HSK), which, in contrast to the epithelial one, is believed to be directed by a predominantly immunopathological process, is one of the leading causes of infectious blindness in developed countries. RESULTS: The mechanisms underlying HSK, and the establishment of viral latency and reactivation are poorly understood. But on the basis of studies with mice as well as clinical immunohistological observations, evidence is now accumulating in support of a cell-mediated mechanism being responsible for corneal destruction. CONCLUSION: Our present knowledge of the pathogenesis of herpetic keratitis is incomplete. The different pathophysiological aspects reflecting our current understanding, such as that of a virally induced autoimmune disease, form the basis of accepted clinical treatment concepts.     

Corneal endothelial changes associated with herpetic stromal keratitis

Wide-field specular microscopy was performed on both eyes of 33 patients with unilateral herpetic stromal keratitis. Endothelial changes were quantitated by computerized morphometric analysis of individual cells. In the 16 patients with disciform keratitis, the corneal endothelium of the affected eyes showed no difference in cell density but demonstrated significant increases of variation in cell size (polymegathism) and shape (pleomorphism) when compared to the cells in the fellow unaffected eyes. The eyes with keratouveitis (17 patients), however, had marked polymegathism and pleomorphism of the endothelium and a distinctly lower endothelial cell density (mean, 19%) than the healthy fellow eyes.     

Antiproteases in herpetic keratitis

Proteolytic enzyme inhibitors are capable of preventing decomposition of the collagen structures of the corneal stroma, and also have a regulating influence on various aspects of the inflammatory process. The content of proteolytic enzymes (alpha 1-antitrypsin and alpha 2-macroglobulin) was studied in the tears and the blood serum of patients with herpes viral keratitis, as well as in the blood serum of rabbits with experimentally-induced ophthalmoherpes. Herpetic keratitis was attended by significant changes in the content of proteolysis inhibitors, as well as in the peripheral blood neutral proteases activity, this presumably serving as a nonspecific blood protective reaction to the inflammation. In the tears of patients suffering from herpetic keratitis the inhibitors are expended for binding activated proteases in the cornea. Local application to rabbits of protein preparations with an inhibitory effect (contrykal, gordox) at the acute period of the experimentally-induced ophthalmoherpes produced a marked antiphlogistic effect.     

Comparative efficacy of three antiviral drugs in mice herpetic keratitis

The antiherpetic effects of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) in vitro and in vivo were investigated in comparison with those of acyclovir (ACV) and 5-iodo-2'-deoxyuridine (IDU). ACV was found to be consistently superior to the other two agents in antiviral activity against all ocular isolates in vitro. In vivo tests in mice, in contrast, showed DHPG in ointment form to be more effective than ACV in treating herpetic keratitis. It was noted that even 0.03% DHPG ointment was as efficacious as 0.3% ACV ointment. Other studies using the same keratitis model also demonstrated that DHPG eyedrop solution is far more effective than IDU eyedrop solution. These results indicate that DHPG can be a useful antiviral agent in the treatment of herpetic keratitis.     

Recurrent herpetic keratitis during topical acyclovir application.

Dendritic herpetic keratitis developed in a 49-year-old patient during topical acyclovir treatment. A positive herpes simplex culture was obtained. After acyclovir was replaced by trifluorothymidine and interferon, the dendritic lesion disappeared and herpes simplex culture became negative. Six months later a carcinoma of the larynx was diagnosed. The acyclovir-resistant herpetic keratitis may be associated with the carcinoma because resistant herpes simplex virus strains are predominantly described in patients suffering from immune deficiency.     

Virus proteins in herpetic keratitis

We examined the differences in protein expression among several strains of herpes simplex virus that cause epithelial and stromal keratitis in the rabbit eye. The isolates were grown in HEp-2 cells in the presence of various radioactive isotopes and were analyzed by SDS-PAGE. The in vitro expression of viral specified proteins was studied with antiserum to the purified virion (heterologous) and with the strain's homologous antiserum made during herpetic ocular disease.We found: (1) similarity among the strains in their in vitro expression of viral proteins; (2) polypeptide differences in the areas of ICP 9/10-ICP 14 and ICP28/29 and 30, when these proteins were immune precipitated with their homologous antisera; (3) more abundant glycosylated polypeptides in the RE (stromal disease-producing) strain than in the F (epithelial disease-producing) strain; (4) secretion of the major glycoproteins (gC, gD and gA, gB) into the extracellular fluid by all tested strains. However, the amounts of the glycoproteins secreted seemed to be characteristic of the individual strain. Those strains that secreted the larger amounts of glycoproteins were the strains that are known to produce stromal disease in the rabbit eye, which suggests that one determinant in the induction of stromal disease may be the number of glycosylated polypeptides as well as the secretion of glycoproteins in a soluble antigenic form.     

Cytokine expression in murine corneas during recurrent herpetic stromal keratitis

Purpose: To describe a case of meningococcemia with anterior uveitis. Methods: Observational case report. Results: A 38-year-old woman developed meningococcal septicemia caused by Neisseria meningitidis type B. During her admission, she had pain in her left eye, inflammatory cells, and a fibrinous exudate in the anterior chamber and multiple posterior synechiae, all in the context of an anterior uveitis. She was treated with topical steroids and mydriatics with resolution of ocular inflammation. Conclusions: This case illustrates the possible association between anterior uveitis and a meningococcal septicemia, and the need for careful ophthalmologic examination when a red eye develops in this clinical context.