Dendritic Ulcers Research Articles

Comparative analysis of ceruloplasmin level in biological fluids at herpes infection

Aim. To compare the levels of ceruloplasmin in tears, saliva and blood serum of patients with herpetic stomatitis and eye herpes to evaluate the effectiveness of treatment. Methods. Ceruloplasmin levels were determined in tears, saliva and blood serum of 30 children, 22 adult patients with herpetic keratitis and 27 children with acute herpetic stomatitis. Biological fluids of 62 healthy individuals were used as the control group. Results. In patients with eye herpes infection, сeruloplasmin levels increased in oral fluid and blood serum and markedly decreased in tears of both affected and intact eye. Ceruloplasmin levels in biological fluids normalized only among children with light forms of eye herpes at discharge. In the case of acute herpetic stomatitis, ceruloplasmin levels increased in oral fluid and blood serum, depending on the severity of the disease. After the treatment, ceruloplasmin levels in tears, oral fluid and blood plasma normalized only in children with dendritic ulcer (herpes epithelial keratitis), while in adult patients with chronic relapsing eye herpes and in children with highly invasive eye herpes ceruloplasmin levels did not normalize. Conclusion. In the case of infection detected multidirectional ceruloplasmin levels in tears, oral fluids and blood serum changes were found in patients with herpes. Ceruloplasmin level decreased in tears, and increased in blood serum and oral fluid.

Collect, boil and amplify – A simple approach for the detection of three common viruses associated with epidemic keratoconjunctivitis, conjunctivitis and dendritic ulcers

During 2011’ an outbreak of epidemic keratoconjunctivitis led to increased clinical requests for molecular screening of viruses from conjunctival swabs. To maximise throughput with minimal cost, a simple boil extraction on dry swabs followed by amplification and real-time detection using ‘in-house’ assays for herpes simplex viruses (HSV) and adenoviruses with RNaseP as an internal control was validated and introduced. Data from 541 patients who were tested for one or more viral targets was analysed. Adenovirus was most frequently detected accounting for 30% of all cases including the community outbreak. Genotyping of the hexon gene identified the cause as an adenovirus type 8. HSV was detected in 7% of the samples tested, predominantly HSV-1 with a single case of HSV-2. Invalid results due to poor RNaseP signals were reported in 10.5% of samples but for the HSV-1 assay 23% of the samples were invalid due to interference of the fluorescein dye used by ophthalmologists resulting in repeat sampling to obtain a valid result. Despite this, when compared to conventional techniques such as direct immunofluorescence, collect, boil and amplify increased significantly the detection of DNA viruses in conjunctival samples ensuring improved diagnosis, patient management and infection control measures at a modest cost.

Herpetic keratitis after corneal collagen cross-linking with riboflavin and ultraviolet-A for progressive keratoconus

To describe a case of herpetic keratitis after corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A for progressive keratoconus. A 31-year-old woman with rapidly progressive keratoconus in the left eye was treated with CXL. Four days postoperatively, a dendritic ulcer developed in the treated eye. The diagnosis was confirmed with polymerase chain reaction analysis of the corneal swab for herpes simplex. The patient had no prior history of herpetic eye disease or cold sores. The keratitis resolved in 10days with treatment. At 1month, the visual acuity was stable, but a mild superficial opacity was noted. Herpetic keratitis can be induced by CXL even in patients with no history of previous herpetic eye disease. Early diagnosis and proper treatment can facilitate successful management of this rare but important complication.

Herpes Simplex and Herpes Zoster associated corneal ulcerations

AbstractCorneal ulcerations are the landmark of viral infections of the ocular surface. The clinical patterns of these ulcerations may vary according to the virus, the type of infection (epithelial or stromal) and the history of the patient. Dendritic ulcers are the most typical findings of Herpes Simplex Virus (HSV) infection, but may also be seen during Varicella‐Zoster Virus (VZV) infection. They share common feature such as rapid diffusion of fluorescein beneath the edges of the ulcer. Inversely, this diffusion is usually not seen in pseudo‐dentritic ulcers, which may be related to either some other infectious agents, or toxicity of eyedrops, or corneal denervation. Geographic ulceration is usually due to HSV infection mistreated with topical steroids, especially if the size of the defect is rapidly progressing. In contrast, a slowly progressing geographic ulcer, with amorphous margins, rather results from neurotrophic conditions. Finally, deep corneal ulcerations, involving both the epithelium and the stroma should be first treated as HSV or VZV necrotic keratitis, but other agents like bacteria, acanthameba and even fungi may lead to similar findings. Such cases thus need a daily control of the evolution to find optimal treatment.

Ganciclovir Ophthalmic Gel 0.15%

Dendritic epithelial keratitis is most commonly caused by infections of herpes simplex virus (HSV) type 1 (HSV-1), and less frequently by HSV type 2 (HSV-2). Ganciclovir, a guanosine nucleoside analogue, is a well established broad-spectrum antiviral agent that inhibits replication of viral DNA and is active against both HSV-1 and -2 and several other viruses. Ganciclovir ophthalmic gel 0.15% is a five-times-daily topical preparation that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers). A randomized, open-label, phase III trial in immunocompetent patients with acute herpetic keratitis showed that ganciclovir ophthalmic gel 0.15% applied five times daily provided effective clinical resolution of dendritic ulcers following 7 days of treatment (primary endpoint). Moreover, a retrospective analysis of noninferiority showed that ganciclovir ophthalmic gel 0.15% was no less effective than aciclovir (acyclovir) ointment 3%. A pooled analysis of three randomized, single-masked, phase II multinational trials also showed high rates of dendritic ulcer healing at day 7 for eyes treated with ganciclovir ophthalmic gel 0.15% and aciclovir ointment 3%. Furthermore, in the individual phase II trials, most patients showed evidence of healed dendritic and geographic ulcers at day 14 in either treatment arm. Median healing times with either treatment ranged from 6 to 10 days. Ganciclovir ophthalmic gel 0.15% was generally well tolerated and was associated with a significantly lower incidence of visual disturbances than aciclovir ointment 3% in the phase III trial.

Outbreak of ocular disease associated with naturally‐acquired canine herpesvirus‐1 infection in a closed domestic dog colony

To describe clinical and virological findings of an outbreak of ocular disease attributed to naturally-acquired primary canine herpesvirus-1 (CHV-1) infection in a closed domestic dog colony. Twenty-seven 10- to 16-week-old laboratory Beagles. Complete ophthalmic examinations were performed and ocular samples collected for CHV-1 polymerase chain reaction and virus isolation. The prevalence of ocular morbidity was 100% in examined dogs. Lesions were restricted to the ocular surface and included bilateral conjunctivitis (100% of dogs); punctate, dendritic, or geographic ulcerative keratitis (26% of dogs); and non-ulcerative keratitis (19% of dogs). Conjunctival petechiae were detected in 22% of dogs. Punctate and dendritic corneal ulcers were frequently organized into discrete groups or linear arrangements. Non-ulcerative keratitis appeared clinically as a perilimbal ring of superficial corneal vascularization and leukocyte infiltration. CHV-1 was detected in ocular samples by polymerase chain reaction or virus isolation in all dogs sampled. In susceptible populations of domestic dogs, CHV-1 may be associated with outbreaks of highly contagious ocular infection in the absence of concurrent overt systemic disease. This naturally-acquired outbreak of CHV-1 infection provides an opportunity to report the spectrum and prevalence of ocular lesions associated with primary ocular CHV-1 infection in dogs. Conjunctivitis was the most frequent ocular lesion detected. Ulcerative and non-ulcerative keratitis were less prevalent and of variable clinical appearance. Dendritic ulcerative keratitis, a classic and relatively specific ocular lesion associated with alphaherpesvirus infection, was detected in < 20% of dogs.

Pediatric Herpes Simplex Virus Keratitis

To report the clinical characteristics and visual outcomes of pediatric herpes simplex virus (HSV) keratitis. The medical records of 29 patients younger than 16 years with HSV keratitis who were diagnosed and treated at Chang Gung Memorial Hospital, Taoyuan, Taiwan, between 1996 and 2004 were retrospectively reviewed. The diagnosis of HSV keratitis was proven by a positive viral culture and/or real-time quantitative polymerase chain reaction or by a clear history of dendritic keratitis or herpetic kerato-uveitis. Type of HSV keratitis, recurrence rate, and visual outcome were analyzed. The average age at the entry into the study was 5.7 years (range: 7 months to 15 years). Mean follow-up time was 35.3 months (range: 2-69 months). Epithelial keratitis including dendritic and geographic ulcers was noted in 14 eyes, stromal keratitis in 2 eyes, stromal keratitis concurrent with epithelial keratitis in 8 eyes, and endotheliitis in 6 eyes. One patient had sequential involvement of both eyes. Thirteen patients (45%) developed recurrent HSV keratitis after the first documented episode. Female gender (but not age or the type of keratitis) was significantly associated with recurrences. Five patients who were maintained on oral valacyclovir prophylaxis up to 1 year had no recurrence during the period. Fifteen of 21 patients younger than 8 years of age had best-corrected visual acuity available at last follow-up, and 10 patients developed amblyopia. Children with HSV keratitis are at risk for recurrent keratitis and amblyopia. Prolonged systemic antiviral prophylaxis may help to prevent such consequences.

Herpes Simplex Keratitis after Ophthalmic Surgery

We report 6 cases of herpes simplex keratitis after ophthalmic surgery, in eyes without clinical history of herpes simplex keratitis. These cases comprised 6 patients examined at our hospital between April 1992 and November 2001. Past operations were keratoplasty in 5 eyes and cataract surgery in 1 eye. Clinical findings and predisposing factors were evaluated retrospectively. The period between herpetic epithelial keratitis onset and ophthalmic surgery ranged from 1.5 to 79 months. Predisposing factors included corticosteroid therapy and operative wound. The herpetic epithelial lesions were dendritic ulcers in 2 eyes, geographic ulcer in 1 eye, and atypical epithelial lesions in 3 eyes; in all cases, herpes simplex virus (HSV)-DNA was detected by polymerase chain reaction (PCR) in tear fluid. All herpetic epithelial lesions healed with oral and topical acyclovir. When corticosteroids are used following ophthalmic surgery, physicians should be alert to the possibility of herpetic epithelial keratitis, even in patients with no clinical history of herpes simplex keratitis. PCR detection in tear fluid is helpful in diagnosing this disease.

Queratitis por herpes simplex tras láser in situ keratomileusis

A 40-year-old woman underwent bilateral Laser In Situ Keratomileusis (LASIK) for the correction of myopia and astigmatism. The day after, four dendritic ulcers appeared in her left eye. She was treated with topical antiviral agents until complete recovery. She had a history of recurrent labial herpetic infection. Reactivation of herpes simplex virus type 1 can occur, even without any previous history of corneal infection. Although this does not contraindicate surgery, all patients with a history of herpetic infection should be made aware of the complications related to this technique.

In vivo confocal microscopy after herpes keratitis.

To describe the confocal microscopic findings, with special reference to corneal subbasal nerves, after herpes simplex virus (HSV) keratitis. 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. 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. 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.

Eosinophilic conjunctivitis, herpes virus and mast cell tumor of the third eyelid in a cat.

A 3-year-old Himalayan cat was diagnosed with concurrent eosinophilic conjunctivitis, herpes virus, and a conjunctival mast cell tumor. Eosinophilic conjunctivitis was verified via cytology from a conjunctival scraping, which revealed 50% eosinophils and 50% neutrophils. Herpes virus was verified via a positive polymerase chain reaction (PCR). Conjunctival scrapings for chlamydia immmunofluorescent antibody (IFA) and herpes IFA were negative. A mycoplasma was detected by a general mycoplasma PCR but the organism did not grow on the available mycoplasma media. The mass was excised and microscopic evaluation revealed a histiocytic mast cell tumor. The mast cell did not recur following local excision (at 1 year follow-up). The eosinophilic conjunctivitis was treated with both topical steroids and systemic megesterol acetate (Ovaban). When topical steroids were used, the herpes virus flared up and resulted in dendritic and geographic corneal ulceration. Therefore, the cat was treated with megesterol acetate and the eosinophilic conjunctivitis was well controlled. Treatment of eosinophilic conjunctivitis in the cat with megesterol acetate may be the treatement of choice due to the possibility of herpes virus.

Classification of herpes simplex virus keratitis.

We propose a nomenclature for classification of herpes simplex virus (HSV) keratitis. We hope that a more consistent classification system will lead to a better understanding of the disease processes, thus resulting in improved diagnosis, treatment, and patient outcomes. A review of the literature was performed to evaluate current HSV classification systems. These systems were evaluated in the context of both current clinical and basic science studies and our own clinical observations. The proposed classification system is based on the anatomy and pathophysiology of the specific presentations of HSV keratitis. Anatomically, the primary level of corneal involvement, whether epithelium, stroma, or endothelium, must be elucidated. Pathophysiologically, the cause of the inflammation. whether immunologic, infectious, or neurotrophic, must be determined. There are four major categories of HSV keratitis. (1) Infectious epithelial keratitis, which is made up of cornea vesicles, dendritic ulcer, geographic ulcer, and marginal ulcer. (2) Neurotrophic keratopathy, which includes punctate epithelial erosions and neurotrophic ulcer. (3) Stromal keratitis, which is subdivided into necrotizing stromal keratitis and immune stromal keratitis. (4) Endotheliitis, which has three clinical presentations: disciform, diffuse, and linear. We believe that by categorizing cases of HSV keratitis by their primary anatomic and pathophysiologic etiologic characteristics, clinicians can better understand and therefore treat all types of HSV keratitis. The four main categories of HSV keratitis are infectious epithelial keratitis, neurotrophic keratopathy, stromal keratitis, and endotheliitis. Each of these is subdivided to more specific clinical presentations.

The management of corneal abrasions in accident and emergency

Recent debate over the use of eyepads and mydriatics for corneal abrasions in ophthalmology departments (Mindin et al., 1996, JAMA 1996; 27: 837) has prompted this review of the management of small corneal abrasions ( < 60% of cornea) in a large teaching hospital accident and emergency (A&E) department. Ninety-nine patients were studied who presented to the Leicester Royal Infirmary A&E Department with a corneal abrasion: 49 were given an eye pad and 50 were not given an eye pad. All patients received chloramphenicol (1%) ointment. There was no significance difference between the two groups in terms of the duration of pain (p > 0.2). Four patients developed corneal infections (two wore an eyepad, two had no eye pad). There was only one patient who suffered a transient but significant reduction in visual acuity ( 6 9 - 6 18 ), following the use of an eye pad and subsequent diagnosis in eye casualty of a dendritic ulcer. It is concluded that accident and emergency treatment of small corneal abrasions is safe and effective if an eye pad is not given. Previous criticisms of A&E management of eye problems (Nayeen and Stansfield, Archs Emerg Med, 1992; 9: 257) are unfounded in this department.

Topical Cyclosporin as an Adjunct to Topical Acyclovir Treatment in Herpetic Stromal Keratitis

Immunological factors play an important role in the development of herpetic stromal keratitis. T lymphocytes are the principal cells involved in this immunologic reaction. We therefore investigated the efficacy and safety of topical cyclosporin A 2 % solution in herpetic stromal keratitis. Ten patients with herpetic stromal keratitis received topical cyclosporin A 2% 4 times daily for 2 months. Acyclovir 3% ointment 5 times daily and cycloplegic eyedrops 2 times daily were used in conjunction with cyclosporin A solution in the 1st month of treatment. Topical steroids were not used. The patients were followed for 6-9 months. Treatment efficacy was evaluated according to two parameters: resolution of stromal infiltrates and neovascularization and increase in visual acuity by two or more Snellen lines. Serum cyclosporin A levels were measured with high-performance liquid chromatography. In all the patients, the stromal infiltration resolved completely after 2 months of treatment. Visual acuity increased by two or more Snellen lines in 8 out of 10 patients. In the remaining 2 cases, stromal scarring that was present before cyclosporin A treatment prevented vision increase. There were no serious complications from the cyclosporin treatment but 4 cases complained of severe burning upon instillation of the drug. This complication was temporary and did not result in discontinuance of the drug. Serum levels of the drug were always below toxicity levels. While this is a noncontrolled study, our results show that topical cyclosporin can be a valuable adjunct to acyclovir treatment in herpetic stromal keratitis. Use of topical cyclosporin in dendritic herpetic ulcers and necrotic stromal keratitis has not been investigated in this study.

Clinical evaluation of carbocyclic oxetanocin G eyedrops in the treatment of herpes simplex corneal ulcers.

Acyclovir (ACV) ophthalmic ointment is effective in the treatment of herpetic keratitis. However, when applied, the ointment has an unpleasant feeling and some cases are resistant to ACV. A new antiviral compound, carbocyclic oxetanocin G (C.OXT-G) has potent anti-herpes simplex virus activity and high water solubility, so the clinical effect of C.OXT-G eyedrops on ulcerative herpetic keratitis was evaluated. Studies were conducted on the corneal ulcers in 37 eyes of 27 patients. Patients with typical dendritic or geographic corneal ulcers were treated with 0.1% C.OXT-G eyedrops, applied five times a day, together with eyedrops of an antibiotic applied four times a day. The eyes were examined at least twice a week until the ulcers healed, and thereafter at intervals for up to 3 months. All of the ulcers healed, their average healing time being 4.9 (SD 2.2) (range 2 to 9) days. The ulcers in 20 of the 37 eyes were induced by the use of corticosteroid or immunosuppressive drugs, and their average healing time was 4.8 (2.3) days. No adverse drug reactions were seen during the observation period in this trial. Eyedrops containing 0.1% C.OXT-G are excellent and safe for treatment of herpes simplex corneal ulcers in humans.

Treatment of cats with ocular disease attributable to herpesvirus infection: 17 cases (1983–1993)

Summary Medical records of 17 cats with ocular disease attributable to herpesvirus infection were reviewed. Herpesvirus infection was confirmed by a positive result on an immunofluorescent antibody test or by detection of dendritic corneal ulcers. Cats were 3 months to 23 years old (mean, 4.8 years). Sex or breed predilections were not evident. Vaccination history was available for 13 cats, 9 of which had been adequately vaccinated against feline viral rhinotracheitis, calici, and panleukopenia viruses. Six cats had a history of respiratory tract disease. Twelve cats were tested for FeLV, and 3 had positive results; 7 cats were tested for feline immunodeficiency virus, with 1 positive result. The most common ocular abnormality seen was conjunctivitis (13/17 cats), followed by dendritic corneal ulcers (10/17 cats). Keratitis was detected in 6 of 17 cats, and nondendritic corneal ulcers in 3 of 17 cats. Corneal sequestra were evident on initial examination or developed during the follow-up period in 4 of 17 cats. Keratoconjunctivitis sicca was diagnosed in 2 of 17 cats, and anterior uveitis was evident in 1 of 17 cats. All cats had 2 or more clinical ocular abnormalities associated with herpesvirus infection. Treatment with topically applied antiviral medications was instituted in 14 cats, including idoxuridine in 7, vidarabine in 4, and trifluridine in 3. Antibiotics were used topically in 10 cats, and atropine was used in 3 cats. Topical administration of corticosteroids was used in 2 cats. Recombinant human α-interferon was given orally to 3 cats in conjunction with topical administration of antiviral agents. In addition to medical treatment, 4 cats were treated surgically. The 17 cats were reexamined 1 to 9 times (mean, 3 reexaminations). Follow-up monitoring (reexamination) was performed between 1 week and 3 years after initial treatment. Ocular disease resolved in 3 of 17 cats, 8 had clinical improvement, and 6 did not have improvement or became worse. A specific antiviral treatment regimen that was clinically superior to other treatments could not be identified.

Herpes simplex keratitis in children.

Ophthalmic findings are reported in 31 eyes of 28 children with herpes simplex keratitis. Twenty two had dendritic ulcers, and nine had geographic ulcers or disciform stromal keratitis. After resolution of keratitis, 80% (19/22) of children with dendritic ulcers achieved corrected visual acuity of 6/9 or better, 50% (11/22) had induced astigmatism, 45% (9/22) had one to five recurrences. In the group with geographic or disciform lesions, 89% (8/9) had reduced corrected vision, 78% (7/9) had induced astigmatism which was predominantly against the rule, and 87% (7/9) had one to six recurrences.

Size dependent variation in the fractal dimensions of herpes simplex epithelial keratitis.

Dendritic ulcers, the commonest manifestation of herpes simplex epithelial keratitis (HSEK) are fractals. It is likely that their fractal properties alter if they progress to a geographic appearance. This study investigates the relationship of maximum ulcer diameter (Feret's diameter) to area (Dm) and perimeter fractal dimensions (Ds), parameters of the complexity of their areas and outlines respectively. For dendritic ulcers in the size range of 1.6-3.2 mm, Dm = 1.41 +/- 0.06 and Ds = 1.40 +/- 0.04 (mean +/- SD). With increasing ulcer size, a progressive divergence of the values of Dm and Ds occurred, such that values of 1.75 and 1.22 respectively were found at a maximum diameter of 8.4 mm. These results imply that as ulcers enlarge, their outlines become less irregular and they fill more of a 2-dimensional plane. Dm and Ds are useful parameters in quantifying the progression of HSEK from dendritic to amoeboid morphology and could have a role in the assessment of ulcer response to pharmacological intervention. A knowledge of the fractal properties of HSEK may increase understanding of the mechanisms of ulcer formation and viral spread.

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.

Herpetic keratitis in Tanzania: association with malaria.

Of 103 patients who presented to a rural clinic in Africa with corneal ulceration, 62 (60.2%) had corneal ulcers which on clinical diagnosis were attributable to herpes simplex virus. There was a strong association between herpetic ulceration and a history of recent malaria; 37 of 62 (59.7%) herpetic ulcers occurred in the 3 month period from April to June which corresponds to the end of the peak season for malaria compared with 14 of 41 (34%) of the non-herpetic ulcers. Fifty per cent of herpetic ulcers had a geographic morphology, 27.4% were dendritic, and 22.6% presumed herpetic ulcers were stromal: 38.7% of herpetic ulcers occurred in children under 5 years of age. Bilateral herpetic ulcers occurred in 16.1% of patients but were more common in children under 2 years of age. Geographic and stromal ulcers tended to heal more slowly than dendritic ulcers (mean time to healing 12.6, 12.2, and 6.6 days respectively), and were more likely to result in severe corneal scarring (45%, 29%, and 0% respectively). Herpes simplex keratitis is a major cause of corneal scarring in Africa. It is often seen in children, may be bilateral, commonly is geographic in morphology, and has a strong association with malaria infection. Because it is not easily preventable, more effort must be made to ensure early diagnosis and prompt, effective treatment in order to prevent severe scarring and visual loss.