Corneal surface changes in Thygeson's superficial punctate keratitis: a clinical and non-contact photomicrographic in vivo study in the human cornea.

PURPOSE: To elucidate mechanisms behind the morphology of Thygeson's superficial punctate keratitis (TSPK). METHODS: Sixteen patients were examined with the slit lamp and photographed by non-contact photomicrography. The results were compared with morphology of epithelial keratitis in herpes simplex type 1 (HSV1), varicella zoster (VZV), and adenovirus type 8 (Ad8) infections, all previously studied by the same method, and with published histologic findings in TSPK. RESULTS: In the photographs, the corneal epithelium showed various numbers of abnormal subsurface cells measuring about 10-15 microm in diameter, present individually, in small groups, or aggregated in larger lesions (coarse lesions with the slit lamp). The surface epithelium was well preserved, except in larger lesions, which showed surface debris. The morphology was unlike HSV1 and VZV epithelial keratitis, but strongly resembled epithelial changes occurring in Ad8 infections on day 5, and later, after the onset of symptoms. CONCLUSIONS: TSPK shows a more widespread epithelial involvement than suspected with the slit lamp. Its morphology seems to reflect an action of a noxious agent targeted at the deeper epithelial layers, with the appearance of abnormal cells as a result. These might represent invading inflammatory cells, damaged intraepithelial ones, or both. The coarse lesions visualize areas of major involvement showing discernible signs of cell destruction. The similarity to Ad8 keratitis suggests that the source of the noxious agent might be located outside the cornea. The morphology, in conjunction with clinical features, is compatible with an immunologically mediated injury. The etiology remains unknown.

Filamentary keratopathy: a non-contact photomicrographic in vivo study in the human cornea.

PURPOSE: To investigate in vivo morphology of corneal filaments. MATERIALS AND METHODS: Over a 12-year period, 19 patients with corneal filaments (7 with keratoconjunctivitis sicca and 12 with other surface diseases) were examined with the slit lamp and photographed by non-contact photomicrography. RESULTS: The filaments appeared as variously long and thick threads, attached at one or both ends to the surface and carrying various amounts of granular and amorphous material. The attachment points and their surroundings showed abnormal cells and diffusion of tear fluid stained green with fluorescein sodium. The underlying stroma appeared normal. The remaining epithelium often showed abnormal surface cells and/or edematous or cystic changes. CONCLUSIONS: The in vivo morphology of filamentary keratopathy is consistent with aggregations of mucus and cell debris adhering to the corneal surface. The underlying diseases seem to have in common corneal epithelial edema. The nature of additional factors, or their combination, precipitating mucus adherence to the surface is not clear.

Corneal surface changes in keratoconjunctivitis sicca. Part I: The surface proper. A non-contact photomicrographic in vivo study in the human cornea.

PURPOSE: To describe corneal surface changes in keratoconjunctivitis sicca (KCS). METHODS: In all 23 patients with KCS were examined with the slit lamp and photographed by non-contact photomicrography. RESULTS: Without staining, grey surface cells and small epithelial cysts were visible. Application of fluorescein sodium resulted in two types of micropunctuate (15-30 microm) staining, a nonfluorescent (yellow/brown) and a fluorescent (green) one, in brilliantly green staining of cysts, and in enlarging fluorescent (green) flecks (70-1600 microm) with propensity to confluence. The flecks often developed in inconspicuous areas and showed abnormal subsurface cells. Application of rose bengal resulted in more or less intensively red-stained cells measuring about 30 mm in diameter, often less (15-20 microm), with or without a centrally located nucleus, individual or gathered in small groups or larger patches, and in confluent staining. Smaller and larger cells, with or without nuclei, weakly or strongly stained, were often located close to each other. The smaller green flecks showed a few centrally located red-stained cells, and the larger ones showed many almost uniform small red-stained nucleated ones. CONCLUSIONS: Corneal epithelial surface disease in the present KCS patients consisted of unspecific features-such as increased light-reflecting property (grey cells), disruptions of intercellular junctions (micropunctuate green fluorescein staining), pathological dye uptake (micropunctuate yellow/brown fluorescein and red rose bengal stainings), and epithelial oedema (microcysts)--and also of features that seemed to be disease specific. Such features were, with fluorescein sodium, focal disruptions of the epithelial barrier function manifesting in enlarging green flecks, and, with rose bengal, abundant nucleated cells, particularly small ones organised in foci. The nature of the abnormal subsurface cells present in the areas of the green flecks, and the mechanisms behind the focal involvement are unclear.

Corneal surface changes in keratoconjunctivitis sicca. Part II: The mucus component. A non-contact photomicrographic in vivo study in the human cornea.

PURPOSE: Description of mucus on the corneal surface and in the precorneal tear film in keratoconjunctivitis sicca (KCS). METHODS: In all, 24 patients with KCS examined with slit lamp and by non-contact photomicrography. RESULTS: Material interpreted as mucus seemed to exist in three varieties: one optically dense, light reflecting, and with definite forms (fine threads, variously thick and long strands, sheet-like structures); one appearing as small clumps or patches of light-reflecting material adhering to the corneal surface; and one amorphous. All were present either per se, or in various combinations, with or without adherent cell debris. The mucus attached to abnormal (stainable) corneal surface cells. CONCLUSIONS: The formed material strongly resembles formed mucus found in samples from normal conjunctival surface; the light-reflecting clumps or patches adhering to the surface are possibly of the same origin. The nature of the amorphous material is unclear. Adherence of formed mucus to the corneal surface seems to be related to the presence of abnormal (stainable) surface cells.

Corneal epithelial keratitis in herpes zoster ophthalmicus: "delayed" and "sine herpete". A non-contact photomicrographic in vivo study in the human cornea.

PURPOSE: To investigate the origin of corneal epithelial keratitis occurring without accompanying herpes zoster ophthalmicus (HZO) cutaneous rash. METHODS: Corneal epithelial lesions in seven patients (four with a history of classical HZO with cutaneous rash, one of herpes zoster oticus, and two with no history of herpes zoster, were examined with the slit lamp and photographed by non-contact in vivo photomicrography. The findings were compared with lesions in classical acute HZO. Polymerase chain reaction (PCR) was done in three patients. RESULTS: Slit lamp appearance, morphology at higher magnification, and kinetics of the lesions were indistinguishable from classical acute HZO. PCR was positive for varicella-zoster virus DNA in all three samples. CONCLUSIONS: The findings strongly suggest that HZO typical corneal epithelial lesions occurring in the absence of cutaneous rash are in fact recurrent episodes of virus shedding.

Healing of recurrent herpes simplex corneal epithelial lesions treated with topical acyclovir A non-contact photomicrographic in vivo study in the human cornea.

PURPOSE: To examine morphological changes occurring in recurrent herpes simplex virus (HSV) epithelial keratitis after the application of topical acyclovir ointment 3%. MATERIAL AND METHODS: 7 patients examined with the slit lamp and photographed by non-contact in vivo photomicrography. RESULTS: Within one day of treatment the lesions lost their typical herpetic features, and after about 2-3 days the morphology seemed to reflect only the sequelae: unhealthy epithelium and abnormal cells located at the level of the basement membrane. Two patients showed epitheliopathy compatible with the side-effects of the treatment. CONCLUSIONS: The rapid loss of typical HSV features after drug application reflects a successful arrest of the virus replication, freeing the epithelial healing forces. At what point of time infectious virus is eradicated and the treatment can be safely stopped cannot be determined clinically. Healing in the sense of restitution ad integrum is a slow process showing individual variations. Abnormal intra-/subepithelial cells are last to disappear.

Corneal epithelial changes due to adenovirus type 8 infection. A non-contact photomicrographic in vivo study in the human cornea.

PURPOSE: To investigate corneal epithelial changes in human adenovirus type 8 (Ad8) infection, and compare them with herpes simplex virus type 1 (HSV1) changes. MATERIAL AND METHOD: 12 patients with Ad8 infection: in 10 verified by tissue culture, in 2 clinically. The corneae were photographed by non-contact photomicrography. RESULTS: Within the first days the epithelium showed multiple elevations measuring about 20-30 microm in diameter, and from about day 5 large numbers of scattered subsurficial abnormal cells. At the end of the first week larger (about 150-200 microm in diameter) epithelial foci started to appear. No focal ulcerative changes were observed. CONCLUSIONS: The subsequent stages of Ad8 cytopathic effect are difficult to discern. The primary virus target seems to be the deeper epithelial layers. The damaged cells are probably successively transported toward the surface and desquamated. The etiology of larger focal changes is unclear. The presence (HSV1) or absence (Ad8) of ulcerative changes differentiates these two infections.

Morphology of epithelial keratitis in herpes zoster ophthalmicus. A non-contact photomicrographic in vivo study in the human cornea.

PURPOSE: To investigate the in vivo morphology of epithelial changes in acute herpes zoster keratitis. METHODS: 10 patients with acute disease. In 7, systemic acyclovir treatment was started at presentation, in 2 < or = 24 hours before, 1 was not treated. The corneae were examined with the slit lamp, followed intermittently for 3-30 days, and photographed at intervals ranging between 1 to 7 days. RESULTS: All but one patient had epithelial changes at presentation; all developed new ones. The smallest discernible entities were abnormal cells of about 10-15 microm in diameter, singular or grouped. Larger foci measured about 100-200 microm. 2 patients showed pseudodendrites at presentation, and further 3/9 observed > or = 2 weeks developed them. Some lesions showed white surface plaques. No ulcerations were observed. Healing occurred < or = 10-22 days after the onset of symptoms. CONCLUSIONS: The study seemed to have followed the natural course of the disease. The rapidly changing morphology in the absence of ulcerative features indicated successive damage counteracted by reparative forces.

Epithelial changes in early primary herpes simplex virus keratitis. Photomicrographic observations in a case of human infection.

PURPOSE: To report the morphology of early corneal epithelial changes in primary herpes simplex virus type 1 (HSV 1), and to compare it to that of recurrent HSV 1 and adenovirus keratitis. METHODS: A 23-year-old man examined with the slit lamp and photographed by non-contact in vivo photomicrography. RESULTS: 3 days after onset the cornea showed myriads of clear epithelial vesicles, two rounded limbal epithelial foci, and scattered, faintly discernible incipient ones. On day 5 several partly confluent foci, and on day 6 typical HSV dendrites were present. HSV 1 was isolated. Serological tests confirmed primary disease. CONCLUSION: The early stage of primary HSV epithelial keratitis differed from recurrent disease by the presence of large numbers of clear vesicles. The photographs, however, captured similar early changes as in recurrent disease, and the subsequent development followed the same pattern. The main sign differentiating primary HSV from adenovirus infections was the early presence of epithelial foci with ulcerative features.

Corneal stromal infiltrates in patients with recurrent erosions.

PURPOSE: To report six patients with recurrent erosions and apparently sterile anterior stromal infiltrates. METHOD: The patients were examined in the slit lamp. RESULTS: The infiltrates resolved slowly in one patient treated only with antibiotics, and more rapidly with the addition of topical steroid treatment in five. In one patient, shortly after the resolution, a new infiltrate appeared in a different site. Another patient suffered a year later a new, but uncomplicated episode of recurrent erosion. Three patients developed during the course of the disease a late phenomenon of nummular superficial opacities which disappeared spontaneously. 5/6 patients had anterior basement membrane dystrophy. CONCLUSIONS: The clinical features are suggestive of a non-infectious process. The striking similarities in the patients' history and clinical picture imply a causative relationship with recurrent erosions. The inflammatory reaction, possibly occurring only in predisposed individuals, seems to be provoked by epithelial breakdowns. The nature of the stimulus is uncertain, but it might be of epithelial origin.

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.

Toxic effect of rose bengal dye on the living human corneal epithelium.

PURPOSE: To investigate whether rose bengal dye at a concentration of 1% has a toxic in vivo effect on the human corneal epithelium. MATERIAL AND METHODS: 80 patients with presumed keratoconjunctivitis sicca (KCS) were examined with break-up time, Schirmer 1 test, and staining with fluorescein sodium and rose bengal. The corneal surface was observed in the slit lamp and photographed by means of non-contact photomicrography. RESULTS: After the application of rose bengal 1% in eyes preinstilled with fluorescein sodium 1% myriads of green dots appeared on the corneal surface in all 32 patients with KCS according to Copenhagen criteria, in 17/18 with low Schirmer 1 test values only, and in 21 of the remaining 30 in whom the KCS diagnosis wasn't verified. CONCLUSIONS: The appearance of green microdots after the application of rose bengal was probably due to the interruption of intercellular junctions and the penetration of fluorescein stained fluid below the superficial cells. Whether this phenomenon reveals an unhealthy corneal surface and thus has a clinical significance has to be further investigated.

Micropunctate fluorescein staining of the human corneal surface: microerosions or cystic spaces? A non-contact photomicrographic in vivo study.

PURPOSE: To study in vivo the phenomenon of micropunctate fluorescein staining of the human corneal surface. METHODS: Patients were examined in the slit-lamp and photographed by the means of photomicrography. The staining pattern of fluorescein was compared with that of superimposed rose bengal staining. RESULTS: The staining patterns showed a great correspondence. CONCLUSION: The findings indicate that micropunctate fluorescein staining probably reveals disruptions of intercellular junctions permitting penetration and accumulation of stained fluid beneath diseased cells in situ.

Keratoconjunctivitis sicca, autoimmune diseases and adenovirus type 8 infection.

In epidemic keratoconjunctivitis caused by adenovirus type 8 (Ad8), 21 patients were followed between 1.5-18 months. Thirty-three percent of the patients developed classical corneal subepithelial opacities. In considering comorbidity possibly influencing the outcome of the disease it was found that: (1) two patients with keratoconjunctivitis sicca did not develop subepithelial opacities, (2) 6/9 patients showing little propensity for developing subepithelial opacities were found to have a variety of manifest diseases of autoimmune nature, and, (3) dense opacities developed in five subjectively healthy persons. These findings suggest that susceptibility to stromal keratitis in Ad8 infections might at least in part be determined by the condition of the host immune status.

Two outbreaks of adenovirus type 8 keratoconjunctivitis with different outcome.

In 1993, a case of adenovirus type 8 keratoconjunctivitis acquired in Central Europe was the starting point of an outbreak in Malmö, Sweden. Of the 33 diagnoses cases, 23 were infected nosocomially. In 29 the diagnosis was verified by virus culture. The outbreak was recognised 15 days after the appearance of the first secondary case. Nosocomial transmission was stopped by protective measures which didn't include separation of the infected patients from others. Epidemiologic investigation disclosed unrecognised infections as the main source of virus transmission; contaminated hands and a dropper bottle appeared to be major vectors. A new case of adenovirus type 8 infection, again introduced from Central Europe, turned up in September 1994. There was only one secondary case.

Herpes simplex virus in chronic relapsing keratoconjunctivitis.

In a patient with a 5-month history of chronic relapsing keratoconjunctivitis, herpes simplex virus antigen was disclosed by immunofluorescence test in material obtained by conjunctival scraping, and the symptoms resolved following acyclovir (Zovirax) treatment. The diagnostic difficulties with patients presenting without symptoms suggestive of herpes simplex virus may be responsible for the lack of similar reports.

Dual appearance of fluorescein staining in vivo of diseased human corneal epithelium. A non-contact photomicrographic study.

Adherence of fluorescein sodium dye to diseased epithelial cells, a hitherto unreported phenomenon, was captured in photomicrographs in severe herpes zoster and keratoconjunctivitis sicca keratopathies. It is notable that this phenomenon differs completely from the well known fluorescent property of the dye penetrating into defective corneal epithelium, and that the staining pattern shown by adherent fluorescein correlates well with the staining pattern shown by rose bengal dye.

Non-traumatic recurrent corneal erosion. A study based on sequential photomacrographic recordings.

A case of non-traumatic recurrent corneal erosion was studied for several days by means of non-contact photomacrography. The development of cysts and fingerprint-like lines was registered. A previous suggestion based on histological evidence regarding the origin of some of the cysts, could be confirmed.

Photography in vivo of epithelial lesions in the human cornea with non-contact high magnification technique.

A technique is described for high magnification in vivo photography of epithelial lesions in the human cornea. Combining use of a high resolution, long working-distance microscope type lens with two-step photographic enlargement techniques results in photomacrographs with effective linear magnification of up to 500 X. The method allows studies of size and shape and crude details of epithelial cells.