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Management of filamentary keratitis associated with aqueous-deficient dry eye.

PURPOSE: To review the incidence, underlying pathophysiology, and clinical features of filamentary keratitis and to identify evidence-based best-practice strategies for managing filamentary keratitis. METHODS: A comprehensive review of published literature was undertaken. Recommendations for best-practice management strategies were based on the available evidence. Three cases are presented to illustrate the clinical findings and management of patients with chronic filamentary keratitis. RESULTS: Although the evidence base is limited by the absence of well-designed studies, current evidence indicates the following: (1) Aqueous-deficient dry eye (keratoconjunctivitis sicca) is the most common ocular condition associated with filamentary keratitis. (2) Current best-practice management of filamentary keratitis involves treating the underlying dry eye and specific treatments for the corneal filaments. Proposed treatments include nonpreserved lubricants, topical steroidal and nonsteroidal anti-inflammatory agents, and punctal plugs for aqueous-deficient dry eye as well as mechanical removal of filaments, hypertonic saline, mucolytic agents, and bandage contact lenses for the filaments. (3) Filamentary keratitis can be induced or exacerbated by contact lens wear and ocular surgical procedures such as cataract surgery and corneal graft surgery. Pre- and postoperative ocular surface management strategies should be considered in the surgical planning of patients with, or who are susceptible to, filamentary keratitis. Filamentary keratitis can also be induced and/or exacerbated by chronic use of ocular and/or systemic medications, and alternate medications or additional measures to manage the tear film and ocular surface may be required in these cases. CONCLUSIONS: Filamentary keratitis can be a chronic, recurrent, and debilitating condition. With a systemic approach to diagnosis and management, the condition can be effectively controlled and the incidence and severity of recurrences minimized.

Adult↗

Impact of differences in diagnostic criteria when determining the incidence of contact lens-associated keratitis.

PURPOSE: The purpose of this study is to examine the effect of differences in within-study and between-study diagnostic criteria in determining the incidence of contact lens-associated keratitis. METHODS: We applied the sets of criteria for "microbial keratitis" as described in five previous studies to the dataset of Morgan et al., which documents 118 cases of contact lens-associated keratitis across a wide range of clinical severities. For each set of criteria, the incidence of contact lens-associated keratitis was calculated for the following five lens type/modality combinations: daily-wear rigid, daily-wear daily disposable hydrogel, daily-wear hydrogel, extended-wear hydrogel, and extended-wear silicone hydrogel. The effect of varying the clinical severity score for the differentiation of nonsevere versus severe keratitis was also examined with respect to the dataset of Morgan et al. RESULTS: The size and location of the corneal infiltrative events identified as representing "microbial keratitis" for each of the different sets of criteria are illustrated in a series of cartograms. A key between-study difference in the incidence values calculated for the various sets of criteria relates to the categories of extended-wear hydrogel and extended-wear silicone hydrogel lenses. Specifically, the incidence of "microbial keratitis" was found to be statistically significantly greater for extended-wear hydrogel compared with extended-wear silicone hydrogel lenses when the set of criteria of Morgan et al. was applied, but not when the other sets of criteria were applied, to the dataset of Morgan et al. Increasing the threshold clinical severity criterion for differentiating between nonsevere and severe keratitis within this dataset resulted in lower incidence values; however, such changes in threshold had a minimal impact on relative risk values. CONCLUSIONS: The choice of criteria for diagnosing contact lens-associated "microbial keratitis" has a significant impact on calculations of the incidence of this condition.

Contact Lenses↗

Detection of herpes simplex virus DNA in atypical epithelial keratitis using polymerase chain reaction.

AIM: To study herpes simplex virus (HSV) DNA in tears from patients with atypical epithelial keratitis of unknown aetiology. METHODS: Tear samples were collected from 17 affected eyes of 17 consecutive patients suffering from epithelial keratitis in whom HSV keratitis was suspected but whose diagnosis was difficult on the basis of clinical manifestations alone. Using reduced sensitivity polymerase chain reaction (PCR), tear samples were tested for HSV DNA. Tears from the unaffected eyes of the 17 patients were also examined, along with 38 tear samples from 19 normal volunteers. Southern blot analysis was performed to confirm that amplified DNA bands were specific for HSV. Clinical correlation with photographs of corneal lesions was also investigated. RESULTS: HSV DNA was detected in tears from the affected eyes of eight of the 17 patients with suspected HSV keratitis. Tears from the affected eyes of the other patients were PCR negative, as were tears from the unaffected eyes of all 17 patients, and from the 38 normal eyes. There was no correlation between PCR results and clinical manifestation of keratitis. CONCLUSIONS: Based on the sensitivity of the PCR system, eight of 17 suspected HSV keratitis patients were confirmed as suffering from HSV keratitis. HSV keratitis should therefore be considered as a possible diagnosis in atypical epithelial keratitis.

Adult↗

[Laboratory study of the mycotic infectious eye diseases and factors associated with keratitis].

PURPOSE: To analyze the frequency and the etiology of mycotic infectious eye diseases diagnosed by culture at the Ocular Diseases Laboratory of the Federal University of São Paulo (LOFT-UNIFESP), São Paulo, SP, Brazil, and the factors associated with fungal keratitis. METHODS: We retrospectively analyzed the 14,391 laboratory requests regarding infectious eye diseases between 1975 and May 2003. For the fungal culture proven examinations we observed the morphologic type of the isolated fungus, the gender and age of the patient, the site of ocular involvement, the year of identification, and the factors associated with keratitis cases, according to the identified etiologic agent. Results were considered significant if p<0.05. RESULTS: We verified 296 (2.05%) ocular mycosis cases with 265 keratitis (89.5%), 27 intraocular infections (9.1%), and 4 infections at other sites (1.3%). Filamentous fungi were isolated in 233 cases (78.7%) 74.7% being male (n=174) and 25.3% female (n=59). Yeasts were isolated in 63 cases (21.3%) 49.2% being male (n=31) and 50.8% female (n=32). Ages varied between 2 and 99 years in the filamentous fungi group and between 14 and 88 years in the yeast group. The most frequently found etiologic agents of the filamentous fungi isolations were Fusarium (n=137; 58.8%), Aspergillus (n=28; 12.0%), and Penicillium (n=12; 5.2%); and in yeasts, Candida (n=59; 93.7%). Regarding keratitis, 95.1% had at least one associated factor. Ocular trauma was significantly associated with filamentous fungi keratitis (p=0.0002); and previous surgeries (p=0.0002), ocular (p=0.0002) and systemic diseases (p=0.0002) with yeast keratitis. The use of topic antibiotics showed association with filamentous fungi keratitis, at a lower statistical significance (p=0.0224). CONCLUSIONS: Laboratory analysis showed predominance of filamentous fungi over the yeasts, and keratitis was the main observed ocular infection. Fungal keratitis involved at least one associated factor in most cases.

Adult↗

[Retrospective analysis of misdiagnosed amoebic keratitis].

OBJECTIVE: To analyze the clinical characteristic of amoebic keratitis and the cause of misdiagnosis retrospectively. METHODS: Corneal pathological sections of 269 cases having been diagnosed as herpes simplex keratitis (HSK), bacterial keratitis and other microbial keratitis and then undergone penetrating keratoplasty (PKP) were reexamined to find the misdiagnosed cases of amoebic keratitis. The clinical characteristic efficacy of treatment and cause of misdiagnosis were retrospectively analyzed according to case history and photographs. RESULTS: Based on the pathological examination, 5 cases of amoebic keratitis were recognized which had been misdiagnosed, including HSK in 3 cases, fungal keratitis in 1 case and suppurative keratitis in 1 case previously. The main clinical characteristics were severe radiating neuralgia and ring-shaped stromal infiltrates. After PKP, infection of 3 cases were controlled, 2 cases were recurrent and underwent eyeball enucleation eventually. CONCLUSION: The incidence of amoebic keratitis is not very low in China. It is necessary to pay high attention to this kind of disease, and its early and definite diagnosis is very important for the prevention of serious results.

Acanthamoeba Keratitis↗

[Clinical forms of acanthamoeba keratitis as viewed from the standpoint of biomicroscopy and confocal microscopy].

Clinical cases of 60 patients with acanthamebic keratitis examined by biomicroscopy and of 22 patients largely examined by confocal microscopy are generalized. Acanthamebic keratitis is a slowly progressing infectious lesion of the cornea, which is caused by acanthamebas freely residing in soil and water. Contaminated contact lenses are the key risk factor. The main clinical features of acanthamebic keratitis are defined; they are presence of risk factors; a unilateral lesion in young, healthy and immune-competent persons; a typical clinical pattern of surface keratitis mainly of the ring shape; corneal neuritis without corneal neovascularization but with a severe pain in the eye; and a slow chronic clinical course, i.e. lasting for several weeks and months. Confocal microscopy is the most effective and fast diagnostic tool because it ensures the detection of acanthamebic cysts and trophozoids in all strata of the corneal stroma. The authors isolate, within the clinical course of acanthamebic keratitis, 5 stages; they are surface epithelial keratitis; surface epithelial punctate keratitis; stromal ring-shaped keratitis; ulcerous keratitis; and keratoscleritis.

Acanthamoeba↗

Fungal keratitis in patients with corneal ulcer in Sari, Northern Iran.

BACKGROUND: Fungal keratitis is a suppurative, ulcerative, and sight-threatening infection of the cornea that sometimes leads to loss of the eye. The objectives of this study were to improve facilities for laboratory diagnosis, to determine the predominant causative microorganisms, and to identify the predisposing factors of mycotic keratitis patients. METHODS: A prospective study of corneal ulcer was conducted in Sari between May 2004 and March 2005. Patients who presented with clinically suspected corneal ulcer to the Ophthalmology Department of Bou-Ali Sina University Hospital in Sari were included in this study. Each patient was examined with slit lamp. Data were collected by examining and questioning the patients. Using standard techniques, corneal scraping was performed by an ophthalmologist. The specimens collected were then smeared on two slides, which were stained with Gram stain (for bacterial keratitis) and 10% potassium hydroxide with or without Calcofluor white stain (for fungal keratitis), and studied under light microscope. The specimens were also inoculated directly on blood agar, Sabouraud dextrose agar, and potato dextrose agar in C-shaped streaks. RESULTS: A total of 22 patients met the inclusion criteria of this study, among whom 10 (45.5%) were females and 12 (54.5%) were males. The mean +/- SD age of patients was 61.5 +/- 17.7 (range: 15 - 83) years. In direct microscopy, branching, and septate hyphae were identified in 7 (31.8%) patients. Two (28.6%) fungi (Aspergillus fumigatus and Fusarium spp.) were isolated. Five (31.8%) patients with fungal keratitis were males and 2 (28.6%) were females. The mean +/- SD age of patients with fungal keratitis was 60.4 +/- 12.1 (range: 39 - 73) years. Three (42.85%) patients with fungal keratitis were farmers. The mean interval between the onset of symptom and diagnosis was 26.4 (range: 1 - 93) days. Trauma with plant debris and straws were noted in two (28.6%) patients with fungal keratitis. Five (71.4%) patients received topical antibiotics. Analyses, using potassium hydroxide with or without Calcofluor white as the gold-standard test, revealed a sensitivity of 71.4% for potassium hydroxide, and 42.9% for Gram stain. CONCLUSION: Infections of the cornea due to filamentous fungi are frequent causes of corneal damage and should always be kept in mind. The direct microscopy method is an essential tool in the diagnosis of fungal keratitis. Therefore, wet mount preparation with potassium hydroxide with or without Calcofluor white or only KOH can be relied upon as the single most important screening test for rapid diagnosis of fungal corneal ulcer.

Adolescent↗

Keratitis.

Corneal inflammation or keratitis is a significant cause of ocular morbidity around the world. Fortunately, the majority of the cases are successfully managed with medical therapy, but the failure of therapy does occur, leading to devastating consequences of either losing the vision or the eye. This review attempts to provide current information on most, though not all, aspects of keratitis. Corneal inflammation may be ulcerative or nonulcerative and may arise because of infectious or noninfectious causes. The nonulcerative corneal inflammation may be confined to the epithelial layer or to the stroma of the cornea or may affect both. For clarity, this section has been divided into nonulcerative superficial keratitis and nonulcerative stromal keratitis. While the former usually includes hypersensitivity responses to microbial toxins and unknown agents, the latter can be either infectious or noninfectious. In the pathogenesis of ulcerative keratitis, microorganisms such as bacteria, fungi, parasites (Acanthamoeba), or viruses play an important role. Approximately, 12.2% of all corneal transplantations are done for active infectious keratitis. Available world literature pertaining to the incidence of microbial keratitis has been provided special place in this review. On the other hand, noninfectious ulcerative keratitis can be related to a variety of systemic or local causes, predominantly of autoimmune origin.

Acanthamoeba Keratitis↗

Conrad Berens Lecture. The management of infectious keratitis as we approach the 21st century.

PURPOSE: To determine the role of cultures in the management of ulcerative keratitis, and to determine the role and selection of either commercially available monotherapy versus combined fortified antibiotics in the treatment of bacterial keratitis. METHODS: The ocular microbiology files at the Bascom Palmer Eye Institute for the years 1969-1997 were reviewed; as were outpatient data at the Bascom Palmer Eye Institute/Anne Bates Leach Eye Hospital for the 20 years 1978-1997 to arrive at an annual incidence of suspected infectious keratitis. An ulcerative keratitis/management survey of the membership of the Castroviejo Cornea Society in 1995 was also conducted. RESULTS: For the period 1969-1997, a total of 5,845 eyes were cultured for suspected infectious keratitis. The incidence of keratitis was 3.1 per 1,000 clinic visits. Forty-nine percent of the cultures were positive--82% bacterial isolates, 16% fungal isolates, and 2% parasites. Pseudomonas aeruginosa represented 20% of the bacterial isolates from 1969 through 1997, increasing to 32% and 39% during the two five-year intervals in the decade 1978-1987, and decreasing to 20% during the period 1993-1997. CONCLUSIONS: 1) Perform corneal scrapings in selected patients with suspected infectious keratitis when risk factors are present, when there is a large central infiltrate, or when empirical therapy has failed. 2) In community/hospital based practice continue to culture all cases of suspected infectious keratitis. 3) Use fortified antibiotics for more severe keratitis. 4) Use monotherapy with a fluoroquinolone and/or other commercially available antibiotics for mild or less suspect keratitis. 5) A third alternative is to combine fortified cefazolin with a fluoroguinolone.

Animals↗

Acanthamoeba keratitis in non-contact lens wearers in India: DNA typing-based validation and a simple detection assay.

OBJECTIVES: To establish that the protozoan Acanthamoeba is one of the causative organisms associated with non-contact lens-related keratitis in the Indian population and to develop a simple and sensitive diagnostic assay for clinical testing. DESIGN: DNA sequencing of nuclear 18S and 26S ribosomal DNA motifs was performed and compared with the reference Acanthamoeba strains, to establish the genetic identity of the putative amoeba isolates obtained from the corneal scrapings of non-contact lens-wearing patients with keratitis. Ribosomal DNA typing of clinical corneal scrapings from the patients with keratitis was performed by means of a simple agarose gel-based multiplex polymerase chain reaction assay, to detect the cases of Acanthamoeba keratitis. RESULTS: The ribosomal DNA analysis of 15 putative amoeba isolates obtained from the corneal scrapings of 14 patients with keratitis and 1 from the patients' environment established the isolates to be pathogenic formsof Acanthamoeba belonging to type T4 ribosomal DNA genotype. Multiplex polymerase chain reaction assay was specific and sensitive enough to detect as low as 5 pg of Acanthamoeba DNA. Its utility as a reliable diagnostic assay was demonstrated directly with the use of 34 additional corneal scrapings. CONCLUSIONS: Acanthamoeba is one of the causative organisms of keratitis in Indian patients with no history of contact lens usage. Moreover, the Acanthamoeba infection can be easily detected in the clinical samples by means of the simple multiplex polymerase chain reaction assay based on ribosomal DNA typing. Clinical Relevance This study suggests the need and means to determine the incidence and prevalance of Acanthamoeba keratitis in India and elsewhere. Moreover, the polymerase chain reaction assay would help in early and definitive diagnosis, leading to better prognosis of Acanthamoeba keratitis condition.

Acanthamoeba↗

Topical anti-inflammatory agents in an animal model of microbial keratitis.

Topical steroids potentiate Pseudomonas keratitis in the absence of concomitant antibiotic therapy. The effects of other anti-inflammatory agents on microbial keratitis are unknown, but if these agents do not intensify the infection, they may be useful in the initial management of microbial keratitis by limiting ulceration and thus the size of the resultant corneal scar. In rabbit models of untreated Pseudomonas keratitis and pneumococcal keratitis, topical 1% prednisolone phosphate, 0.03% flurbiprofen sodium, and vehicle were applied hourly. In cases of Pseudomonas keratitis, prednisolone worsened the clinical disease, and flurbiprofen further worsened the disease. When combined with effective antibiotic therapy, neither anti-inflammatory agent worsened the disease. In pneumococcal keratitis, neither anti-inflammatory agent worsened the disease. Topical anti-inflammatory agents should be used with caution in cases of microbial keratitis at least until effective antibiotic therapy has been instituted.

Administration, Topical↗

Incidence and severity of herpetic stromal keratitis: impaired by the depletion of lymph node macrophages.

HSV-1 induced stromal keratitis (HSK) is an immune-mediated disease. The role of macrophages in this process is still unclear. In this study we investigated the influence of specific macrophage depletion from the spleen and the submandibular lymph nodes by dichloromethylene diphosphonate liposomes (Cl(2)MDP-LIP) on the course of HSV-1 keratitis. BALB/c mice were infected corneally with 10(5)PFU of HSV-1 (KOS). Groups of mice received Cl(2)MDP-LIP 7 and 2 days prior to infection. Cl(2)MDP-LIP were given by various routes: intravenously (i.v.) for macrophage depletion in the spleen; subcutaneously for macrophage depletion in the submandibular regional lymph node (s.c.); or both i.v. and s.c. The development of HSV-1 keratitis was evaluated clinically and histologically. A standard plaque assay from the infected eyes was used to measure virus clearance. Seventy-nine percent of the HSV-1-infected control mice (n = 14) developed severe stromal keratitis by day 14 p.i. The development of stromal keratitis was inhibited by Cl(2)MDP-LIP given s.c. (64%;n = 14;P < 0.05), i.v. and s.c. (50%;n = 14;P < 0.05), but not by i.v. treatment alone (77%;n = 13). After s.c., i.v. and s.c. Cl(2)MDP-LIP injection, histologically the corneal stroma had a decrease in inflammatory cell infiltration by day 14 p.i. compared to the control group, and the DTH response was reduced. The healing of epithelial HSV-1 keratitis and the virus clearance were not affected significantly. These results indicate an important function of macrophages in the course of HSV-1 keratitis. Virus replication in the eye does not appear to be affected by monocytes/macrophages of lymph nodes and spleen. In contrast, the immunopathological process of stromal HSV-keratitis that results in corneal destruction is profoundly accelerated by macrophages in the lymph nodes.

Animals↗

Colletotrichum keratitis.

PURPOSE: To evaluate Colletotrichum keratitis and to report the risk factors and clinical course. DESIGN: Interventional case series. METHODS: In order to report the clinical course of Colletotichum keratitis, fungal keratitis cases between January 1980 and February 2001 in an institutional setting were retrospectively reviewed and 10 eyes of 9 patients with Colletotrichum keratitis were identified by positive cultures. RESULTS: Colletotrichum species were identified in 10 of 360 culture-proven fungal keratitis cases. All cases were sensitive to amphotericin B, three of the isolates showed resistance to natamycin, two isolates had intermediate sensitivity to natamycin, and one isolate was resistant to fluconazole. Natamycin 5% was used as the initial antifungal agent in eight microbiologically proven fungal keratitis cases. Two of nine patients continued the treatment with amphotericin B 0.15% after the sensitivity results were obtained. CONCLUSION: Colletotrichum is an infrequent cause of fungal keratitis. The risk factors are similar to the known fungal keratitis. Colletotrichum is resistant to natamycin in vitro; however, all our patients responded well to this treatment while resistance or intermediate sensitivity to natamycin and resistance to fluconazole was observed.

Adult↗

Latanoprost and herpes simplex keratitis.

PURPOSE: To report three cases in which herpes simplex keratitis developed after initiation of latanoprost therapy. METHODS: Case report. RESULTS: One patient with a history of herpes simplex keratitis had recurrence of herpes simplex keratitis with latanoprost treatment, resolution when latanoprost was stopped, and another recurrence when rechallenged with latanoprost. A second patient with a history of herpes simplex keratitis had bilateral recurrence with initiation of latanoprost; antiviral therapy could not eradicate herpes simplex keratitis until the latanoprost was discontinued. The third patient with latanoprost-associated herpes simplex keratitis cleared with the discontinuation of latanoprost and start of antiviral therapy; reinstitution of latanoprost with prophylactic antiviral medication kept the cornea clear, but as soon as the antiviral suppression was discontinued, herpes simplex keratitis reappeared. CONCLUSION: Latanoprost, among its diverse pharmacologic effects, may mediate inflammation in the eye. Prostaglandins may be a final common pathway for stimulating recurrence of herpes simplex keratitis. Clinicians should be aware of this possible association.

Aged↗

The serratial 56K protease as a major pathogenic factor in serratial keratitis. Clinical and experimental study.

A possible cause and the difference in clinical severity of serratial keratitis were investigated. Two strains of Serratia marcescens were isolated: one from a patient with severe liquefactive keratitis, who had diabetes mellitus, and one from a patient with mild superficial keratitis, but who had no underlying disease. When the same numbers of bacteria were injected separately into corneas of the same rabbits or guinea pigs, the strain from the first patient elicited severe corneal destruction, remarkable intracorneal edema; and liquefactive necrosis, but the strain from the second caused mild keratitis with erosion or intracorneal abscess. The keratitis induced by the former strain required a longer time to heal, and the prognosis was poorer than that for the other keratitis. Therefore, the difference in severity between the two cases of experimentally induced keratitis paralleled that of the clinical cases. Thus, the severity of the serratial keratitis might be attributed more to the virulence of the bacteria than the condition of the host. The virulence factor seemed to be a heat-labile metabolic product (or products) of the bacteria. To clarify this virulence factor, the major secretory protease (56K protease) produced by these two strains of bacteria was compared by using in vitro and in vivo systems. The virulent strain produced about ten times more protease during culture than the less virulent strain. When injected into the corneas of experimental animals, the 56K protease from the virulent strain induced severe lesions similar to those caused by the living virulent strain of bacteria. These results indicated that one of the major factors causing the virulence was correlated with the tissue destructive 56K protease produced by S. marcescens.

Aged↗

Microbial keratitis in children.

OBJECTIVE: Microbial keratitis is a major cause of corneal blindness worldwide. This problem is particularly relevant to children, because most of their visual life is ahead of them, and they are uniquely at risk for irreversible ocular deficits, such as those resulting from amblyopia. The objective of this study was to determine the etiologic agents and predisposing factors in childhood infectious keratitis and to examine the outcome of treatment in terms of structure and visual acuity. DESIGN: The study design was a retrospective cases series. PARTICIPANTS: The authors studied 113 eyes in 107 children 16 years of age and younger who were treated for (nonviral) microbial keratitis at the LV Prasad Eye Institute in Hyderabad, India, during the 4.5-year period between February 1, 1991, and June 30, 1995. INTERVENTION: The patients who met the following criteria were included in the study: (1) corneal stromal infiltrate was present on slit-lamp examination; and (2) a corneal scraping was taken at the time of examination for suspected microbial keratitis. MAIN OUTCOME MEASURES: Etiologic micro-organisms, predisposing factors, treatment method, structural treatment outcome, and visual acuity treatment outcome of the infectious keratitis episode were measured. RESULTS: The principal predisposing factors identified in this study were trauma (21.2%), ocular disease (17.7%), systemic disease (15.9%), and prior penetrating keratoplasty in the same eye (8.8%). Vitamin A deficiency was an important factor within the category of severe systemic disease, and contact lens wear was not involved in any of the cases. A total of 85 organisms were isolated in cultures of corneal scrapings from 64 (56.6%) of the 113 cases. Staphylococcus species (43.7%), Streptococcus pneumoniae (18.8%), and fungi (17.2%) were the most common isolates. Eighteen eyes (15.9%) required surgery, and 28 (36.4%) of the 77 patients on whom visual acuity was assessed at last follow-up achieved an unaided visual acuity of 20/60 or better at last follow-up. CONCLUSION: This work represents the largest recent study on childhood (nonviral) microbial keratitis, its management, and treatment outcomes. In this study, amblyopia is highlighted as a potentially significant sequela of childhood microbial keratitis. Identification of the appropriate predisposing factors, etiologic microbial organisms, and treatment outcome from this study may aid in early recognition and treatment of microbial keratitis in children.

Adolescent↗

Oral acyclovir for the management of herpes simplex virus keratitis in children.

PURPOSE: To evaluate the use of oral acyclovir in pediatric patients with herpes simplex virus (HSV) keratitis. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Seven pediatric patients seen at the University of Minnesota Hospitals and Clinics with herpes simplex virus (HSV) infectious epithelial keratitis between January 1992 and October 1998. Patient ages ranged from 6 weeks to 5 years at time of presentation with a median of 1.7 and mean of 1.9 years. INTERVENTION: All patients received oral acyclovir; six of seven patients also received topical antiviral medications. Three of seven patients had topical antiviral therapy fail before being placed on oral acyclovir, and the remaining four patients were placed on oral acyclovir primarily. RESULTS: All patients showed resolution of HSV infectious epithelial keratitis. Three patients have been maintained on prophylactic dosage of oral acyclovir because of recurrent disease or because they have been chronically treated with topical corticosteroids for immune stromal keratitis. All patients tolerated acyclovir well, and there were no adverse reactions. CONCLUSIONS: Oral acyclovir is useful in treating HSV infectious epithelial keratitis in pediatric patients. It is beneficial in treating infectious epithelial keratitis and prophylactically either while treating with topical corticosteroids for immune stromal keratitis or for preventing recurrent infectious epithelial keratitis.

Acyclovir↗

Increased severity of herpes simplex virus type 1-induced keratitis in Hox A5 transgenic mice.

PURPOSE: Herpes simplex virus type 1 is a major cause of stromal keratitis and blindness in humans. Understanding of the role of host genes in the pathogenesis of herpes stromal keratitis is limited. We used a transgenic mouse model to examine the effect of a host gene, Hox A5 (which binds to the TAATGARAT sequence in the promoter regions of HSV-1 immediate early genes and increases HSV-1 replication), on the pathogenesis of HSV-1 induced stromal keratitis. METHODS: Corneas of wildtype and Hox A5 transgenic mice were infected with HSV-1 strain F following corneal scarification. Clinical severity of keratitis was evaluated using slit-lamp biomicroscopy. Histologic severity of keratitis was determined by light microscopic evaluation and by computerized morphometry. Ocular viral replication was measured via plaque assay. RESULTS: Clinical lesions of stromal keratitis were more severe at 17 and 23 days post infection in Hox A5 transgenic mice than in wildtype mice. Histological evaluation and morphometric analysis confirmed that keratitis lesions were more severe in the transgenic mice. HSV-1 replication was approximately100-fold greater in the corneas of transgenic mice than in wildtype mice. CONCLUSIONS: Our results demonstrate that a host gene (Hox A5) can increase ocular replication of HSV-1 and alter the pathogenesis of herpetic stromal keratitis.

Animals↗