Pseudodendritic fungal epithelial keratitis in an extended wear contact lens user.

PURPOSE: Pseudodendritic keratitis in a contact lens wearer is generally associated with acanthamoeba keratitis. We report a case of isolated pseudodendritic fungal epithelial keratitis that occurred in an extended wear contact lens user. METHODS: A 48-year-old woman was evaluated in our clinic for a 36-hour history of left eye pain. She wore extended wear soft contact lenses and frequently rinsed her eyes with tap water. Her left cornea had a paracentral 3-mm area of epithelium with raised ridges in a pseudodendritic pattern. The underlying corneal stroma was normal. A therapeutic and diagnostic corneal scraping of the lesion was performed and sent for Gomori methenamine silver (GMS) staining. The clinical concern was for epithelial acanthamoeba keratitis. RESULTS: The GMS staining revealed septate fungal hyphae within sheets of corneal epithelium. The patient was started on frequent alternating natamycin (5%) and amphotericin B (0.15%) antifungal eyedrops and exhibited a rapid clinical response. Her keratitis completely resolved, and her vision returned to her baseline of 20/25. Corneal fungal cultures showed no growth. CONCLUSIONS: Our case is an extremely unusual presentation of fungal keratitis, which rarely presents as a pseudodendritic epithelial keratitis. There are two previous similar case reports initially misdiagnosed as acanthamoeba keratitis. Clinicians should be aware that isolated fungal epithelial keratitis can present as a distinct entity and should be considered in the differential diagnosis of pseudodendritic keratitis. The GMS staining is an excellent diagnostic test in a patient presenting with pseudodendritic keratitis because it allows rapid diagnosis of acanthamoeba and fungal infections.

Unusual dendritic keratitis.

Bilateral pseudo-dendritic keratitis in infancy can be due to tyrosinemia, a rare metabolic disorder. Ocular involvement may be the earliest presenting manifestation of this disease. Early diagnosis is essential because dietary modifications can result in complete reversal of the manifestations of this disorder. This disease must be suspected in all cases of non-responsive dendritic keratitis in the pediatric age group, especially if it is associated with cutaneous lesions such as patmoplantar keratosis. Serum tyrosine levels must be done in these cases.

Paciente con enfermedad corneal severa en el contexto del síndrome KID / Patient with severe corneal disease in KID syndrome

Caso clínico: Mujer de 33 años con neovascularizacióncorneal bilateral superficial y profunda yqueratopatía punteada superficial de distribucióndifusa, queratoeritema y sordera neurosensorial,que es diagnosticada de síndrome KID.Discusión: El síndrome KID es una displasia congénitaectodérmica caracterizada por la asociaciónde queratitis vascularizante, lesiones cutáneashiperqueratósicas y sordera neurosensorial. Recientemente,la deficiencia de stem cell limbares ha sidoreconocida como posible factor patogenético clave

Case report: A 33-year-old woman with superficial ;;and deep bilateral corneal vascularization and ;;keratoconjunctivitis sicca, keratoerythema and neurosensory ;;deafness, was diagnosed with keratitisichthyosis- ;;deafness (KID) syndrome. ;;Discussion: KID syndrome is a congenital ectodermal ;;dysplasia characterized by the association of ;;vascularizing keratitis, hyperkeratotic skin lesions ;;and sensorineural hearing loss. Recently, limbal ;;stem cell deficiency was recognized as a possible ;;major pathogenetic factor

[The pathogenesis of herpetic keratitis]. / Zur Pathogenese der herpetischen 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.

In vivo confocal microscopy after herpes keratitis.

PURPOSE: To describe the confocal microscopic findings, with special reference to corneal subbasal nerves, after herpes simplex virus (HSV) keratitis. METHODS: In this study, 16 HSV eyes and 14 contralateral eyes of 16 patients, diagnosed with unilateral HSV keratitis 1-12 months earlier by the presence of dendritic corneal ulceration or microbiologic confirmation, were examined by in vivo confocal microscopy for evaluation of corneal morphology. RESULTS: Herpes simplex virus eyes: In 2 eyes the surface epithelial cells appeared large, and no abnormalities were observed in the basal epithelial cells. In 2 eyes subbasal nerve fiber bundles were completely absent, in 3 eyes there was a reduced number of long nerve fiber bundles, and in 11 eyes the subbasal nerve plexus appeared normal. In 10 corneas, highly reflective dendritic structures were found at the level of the basal epithelial cells. Frequently these structures were found in the vicinity of stromal fibrosis. Areas with increased abnormal extracellular matrix were found in 11 eyes. Stromal nerves were not visualized in all corneas, but appeared normal when observed. Contralateral eyes: No abnormalities were observed in the epithelium. All corneas presented with a normal subbasal nerve plexus, but in 2 eyes dendritic particles were observed. Three corneas presented with activated keratocytes and increased amounts of abnormal extracellular matrix. CONCLUSIONS: When visualized by confocal microscopy, the subbasal nerve plexus appears relatively unaffected in cases with resolved HSV keratitis. Unidentified dendritic structures, presumably Langerhans cells, are frequently seen at the level of the basal epithelium in corneas with a history of herpetic disease.

Comparative antiviral efficacies of cidofovir, trifluridine, and acyclovir in the HSV-1 rabbit keratitis model.

PURPOSE: To determine the relative antiviral inhibitory activity of topical 1% and 0.5% cidofovir, topical trifluridine (Viroptic; Burroughs-Wellcome, Research Triangle Park, NC), and topical acyclovir (Zovirax; The Wellcome Foundation, London, UK) during a 7-day period for the treatment of herpes simplex virus type 1 (HSV-1) keratitis and HSV-1 replication in the New Zealand rabbit ocular model. METHODS: In a series of four experiments using a two-eye design, a total of 80 New Zealand rabbits were inoculated in both eyes with HSV-1 McKrae after epithelial scarification. Forty-eight hours after inoculation, the rabbits were randomly assigned to a treatment group. Five treatment groups (16 rabbits/group) were evaluated: I, 1% cidofovir, twice daily for 7 days; II, 0.5% cidofovir, twice daily for 7 days; III, 3% acyclovir ointment, five times daily for 7 days; IV, 1% trifluridine, nine times daily for 3 days, then 4 times daily for 4 days; and V, control vehicle twice daily for 7 days. HSV-1 dendritic keratitis was graded in a masked fashion by slit-lamp examination on days 2, 3, 5, 7, 9, 11, and 14. Ocular viral cultures were obtained after slit-lamp examination on days 1, 3, 5, 7, 9, 11, and 14. RESULTS: Compared with the control group, all four treatment groups demonstrated significantly lower viral titers, fewer HSV-1-positive eyes/total during the treatment period, lower keratitis scores, fewer eyes with keratitis/total, and a shorter time to resolution of keratitis. Within the treatment groups, the 1% and 0.5% cidofovir treatments were significantly more effective than acyclovir and trifluridine as measured by the previous viral and keratitis parameters. CONCLUSIONS: Topical 1% and 0.5% cidofovir both appeared to be significantly more efficacious than topical trifluridine and acyclovir, during a 7-day course, in the treatment of experimental HSV-1 ocular disease in the New Zealand rabbit keratitis model.

Early epithelial changes in recurrent herpes simplex virus keratitis: a non-contact photomicrographic study in vivo in the human cornea.

PURPOSE: To examine early corneal epithelial changes in recurrent herpes simplex virus (HSV) type 1 keratitis. MATERIAL AND METHODS: Three patients presenting early (< or =18, < or =24 and < or =29 hours) after the onset of symptoms were examined by means of non-contact in vivo photomicrography. RESULTS: Case 1 (< or =18 hours) showed about 60 rounded or irregularly shaped and partly confluent intraepithelial lesions. In case 2 (< or =24 hours) similar lesions and a dendritic figure with a broken pattern were present. Case 3 (< or =29 hours) showed four separate lesions and a large dendrite. Some lesions appeared as dark protrusions in the fluorescein stained tear film, others stained green; of these, some additionally showed fluorescein diffusion into the surroundings. The smallest discernible entities were abnormal cells of about 10 microm in diameter, present both within the lesions and scattered elsewhere, and clearly swollen cells of about 15 microm of diameter. CONCLUSIONS: The distribution of the precursors shows the multifocal origin of HSV dendritic figures. The dark protruding lesions with abnormal cells covered by intact overlying cell layer(s) seem to be the earliest HSV epithelial changes so far captured in the living human cornea. The protrusions are probably the result of cell swelling representing the incipient stage of HSV cytopathic effect, and the subsurface location of the abnormal cells suggests that the initial virus target are the deeper epithelial layers. The morphological features of the remaining lesions are consistent with successive stages of cell degeneration, i.e. cell swelling leading to surface disruptions, burst of the cells, and cell desquamation resulting in surface ulcerations. The contemporaneous presence of all these stages is typical of recurrent HSV type 1 infections.

Chronic varicella-zoster virus epithelial keratitis in patients with acquired immunodeficiency syndrome.

OBJECTIVE: To characterize further a chronic epithelial keratitis caused by varicella-zoster virus infection in patients with acquired immunodeficiency syndrome (AIDS). METHODS: Patients with AIDS and chronic epithelial keratitis associated with varicella-zoster virus from 3 institutions were identified. Patient records were reviewed retrospectively for the following data: medical and demographic characteristics, techniques of diagnosis, physical findings, course, response to treatment, and outcome. RESULTS: Sixteen patients were studied. CD4+ T-lymphocyte cell counts were available in 11 patients, with a median of 0.034 x 10(9)/L (range, 0-0.094 x 10(9)/L). Two patients had no history of a zosteriform rash. In the remaining patients, the interval between rash and keratitis ranged from 0 days to 6 years. In all cases, the keratitis was chronic and characterized by gray, elevated, dendriform epithelial lesions that stained variably with fluorescein and rose bengal. The peripheral and midperipheral cornea was most commonly affected, and, in 13 of the 16 patients, the lesions crossed the limbus. Pain was a prominent feature, occurring in 12 of 16 patients. In 9 of 12 patients tested, varicella-zoster virus was identified by culture, direct fluorescent antibody testing, polymerase chain reaction testing, or a combination of these studies, with direct fluorescent antibody testing (6 of 8 positive results) and polymerase chain reaction testing (3 of 3 positive results) appearing to be the most sensitive. Response to antiviral medication was variable. CONCLUSIONS: In patients with AIDS, varicella-zoster virus may cause a chronic infection of the corneal epithelium. The keratitis is characterized by dendriform lesions, prolonged course, and frequently by extreme pain. It can occur without an associated dermatitis.

Infectivity of basal epithelial cells in herpetic dendritic epithelial keratitis.

In patients with herpes virus dendritic epithelial keratitis, the pathologic morphogenesis of the dendritic lesion was investigated by means of impression cytology. Impression specimens were taken from the lesions of 24 consecutive patients assessed with a slit lamp biomicroscope. After a Millipore membrane impression was stained with hematoxylin-eosin and examined by light microscope, cellular patterns were analyzed. The results of these examinations showed that most cells were epithelial cells; there were also occasional multinucleated syncytial giant cells, inclusion bodies and inflammatory cells. Basal epithelial cells were most prominent at the actively infected lesion, whereas superficial epithelial cells were shown at the margin of the active lesion and terminal bulb. These findings suggest that in dendritic keratitis, viral spread and replication in the dendritic keratitis may progress through basal epithelial cells along the nerve within the basal epithelium-stromal interface.

Effect of 9-(4-hydroxybutyl)-N2-phenylguanine (HBPG), a thymidine kinase inhibitor, on clinical recurrences of ocular herpetic keratitis in squirrel monkeys.

9-(4-Hydroxybutyl)-N2-phenylguanine (HBPG) is a new viral thymidine kinase inhibitor that we tested for the ability to prevent recurrences of herpetic keratitis. Eighteen squirrel monkeys (Saimiri scuireus) were infected in both corneas with the Rodanus strain of herpes simplex virus type 1 (HSV-1). All corneas showed typical dendritic keratitis 3 days after infection, followed by spontaneous healing. On day 21, the monkeys were randomized into two coded groups and ocular examinations were begun. One group received intraperitoneal (i.p.) injections of HBPG, 150 mg/kg, in a corn oil suspension every 8 h, and the other group received i.p. injections of the corn oil vehicle only. On day 22, recurrences were induced by reducing the temperature of the room in the late afternoon so that a low of 18 degrees C was achieved during the night. After the morning treatment, room temperature was raised to the normal ambient temperature (24-27 degrees C), and treatment was discontinued. Treatment was reinstituted on day 27, the room temperature was lowered again on day 28, and treatment was again discontinued as before. Third and fourth cycles of treatment and cold stress were begun on days 34 and 69. Ocular examinations were continued until day 73, at which point the code was broken. We found that the HBPG treatment significantly reduced the number of corneas with recurrences during the treatment periods, compared with recurrences in untreated, cold-stressed animals (P = 0.01).

Clinical characteristics of acyclovir-resistant herpetic keratitis and experimental studies of isolates.

BACKGROUND: We treated two patients with dendritic keratitis that did not respond to acyclovir (ACV) ointment therapy. Their systemic immune status was normal: however, one patient had a long history of atopic disease and the other had previously undergone topical corticosteroid treatment. HSV-1 was isolated from the patients and inoculated into animals to investigate its viral pathogenicity and latent infection. METHODS: HSV-1 isolates from the patients were tested for drug sensitivity to acyclovir, ganciclovir, idoxuridine, trifluridine, foscarnet and interferon-beta in vitro. In in vivo studies, bilateral corneas of two New Zealand white rabbits and 10 BALB/c mice in each of four groups were infected by the respective viral isolates. The extent of corneal epithelial and/or stromal lesions produced by the viruses was evaluated. The trigeminal ganglial tissues of the mice were examined for viral latent infection by co-culture with Vero cells. RESULTS: Herpetic keratitis in both patients was characterized by prolonged clinical course, succeeded by various types of corneal lesions and ocular complications. In in vitro studies, the two HSV-1 isolates demonstrated cross-resistance to ACV, ganciclovir and/or idoxuridine. Both strains demonstrated weakly virulent corneal epithelial and/or stromal lesions in rabbits and mice. One isolate displayed delayed advent but prolonged course of epithelial lesions in rabbits. The latent infection incidences of the isolates in mice trigeminal ganglia were 6.25% (1/16) and 0% (0/18) respectively. CONCLUSION: Topical immune depression may induce ACV-resistant HSV-1 infection in the cornea, with a prolonged course in association with ocular complications. The prolonged infectious course of the viral isolates in the animal study partially supported the clinical demonstrations in the patient. The existence of latent infection by one ACV-resistant HSV-1 in its animals may indicate the possibility of its recurrence. Trifluridine may be an alternative choice for treating corneal epithelial lesions caused by ACV-resistant HSV-1.

Herpetic epithelial keratitis caused by acyclovir-resistant strain.

Dendritic keratitis occurred during oral acyclovir (ACV) therapy in a 60-year-old man. Corneal stromal edema and iritis were found at his first visit. Herpetic keratouveitis was suspected, based on clinical findings and previous history. Treatment with steroid eyedrops and ACV ointment was initiated. However, ACV [corrected] ointment was changed to oral ACV, since conjunctival ulcer occurred as an adverse effect of the ointment. Subsequently, he received long-term oral ACV medication and steroid eyedrops for recurrent keratitis. The fifth recurrence was also treated with oral ACV and steroid eyedrops. At this time, although the stromal keratitis had improved, there was an outbreak of dendritic keratitis. The lesion healed spontaneously after only a reduction in the steroid. The 50% effective dose (ED)50 of the isolated virus to ACV was 4.4 +/- 0.15 micrograms/ml (mean +/- SD), a level considered ACV-resistant in vitro. The clinical course of this case emphasizes that it is important to consider the route and duration of ACV administration and the use of steroids in the treatment of stromal keratitis or keratouveitis.

Fractal properties of herpes simplex dendritic keratitis.

Fractal geometry can be used to analyze the complexity and self-similarity of many natural forms and structures. By using three techniques for fractal dimension estimation, a group of 11 herpes simplex virus dendritic corneal ulcers was analyzed and found to possess outlines with fractal properties. The mean surface fractal dimension approached 1.4 over 1.5 decades of scale. The demonstration and quantification of the fractal dimension of dendritic lesions is important in the understanding of their behaviour and, at a more fundamental level, the planar spread of viral infection.