Laboratory diagnosis in ulcerative keratitis

AIMS: To identify the common bacterial and fungal isolates from corneal ulcers and to determine the antimicrobial susceptibility patterns of bacterial isolates to commonly used antibiotics at B.P. Koirala Institute of Health Sciences (BPKIHS), eastern Nepal. Culture and direct microscopic correlation and reliability were also compared. METHODS: All patients with suspected corneal ulceration presenting to the Ophthalmology Department of BPKIHS from 1st August 1998 to 31st July 2001 were evaluated. Corneal scraping was performed and processed for direct microscopy and culture for bacterial and fungal isolates. Bacterial isolates were subjected to antimicrobial susceptibility testing. RESULTS: Of 447 specimens examined direct microscopy was positive in 216 (48%) specimens. Culture positivity could be correlated with direct microscopy in 179 (83%) of specimens. Growth of etiologic agents was found in 303 (67.8%) samples. Of these 145 (47.8%) had pure fungal growth, 103 (34%) had pure bacterial growth and 55 (18.2%) had mixed fungal and bacterial infection. The commonest fungal pathogen was Aspergillus spp.in 78 (38.4%) followed by Fusarium spp. in 45 (22%). Aureobasidium sp. was isolated in 25 (12.3%) samples. Staphylococcus aureus (93, 56.7%) dominated the scene as the commonest bacterial agent. Streptococcus pneumoniae (33, 20%) was second in the list. Most of the bacterial isolates were sensitive to commonly used antibiotics. CONCLUSION: This study emphasizes the importance and need of the continued surveillance of the agents and their antimicrobial susceptibility for the prevention and management of corneal ulcers and their complications.     

Predisposing factors in microbial keratitis: the significance of contact lens wear.

Fifty-three patients consecutively admitted to Moorfields Eye Hospital for treatment of suspected microbial keratitis were examined to identify predisposing factors. The principal associations were pre-existing corneal disease (22 patients (41.5%] and contact lens wear (22 patients (41.5%]. In 13 cases (25%) contact lens wear was the only factor in patients with otherwise healthy eyes using contact lenses as an alternative to spectacles. Gram-negative keratitis was more frequent in the lens wearers, with the exception of therapeutic lens users, than in other patients (p = 0.0006) and Pseudomonas aeruginosa caused keratitis in cosmetic soft lens users more frequently (p = 0.001). There was no correlation between lens handling or solution contamination in three extended wear soft-lens users. This implies that some soft-lens wearers may be infected by Gram-negative organisms from environmental sources other than contaminated lens care materials. Gram-negative keratitis is strongly associated with contact lens wear, and the diagnosis must be considered in any contact lens user with an acutely painful red eye.     

Peripheral ulcerative keratitis

Peripheral ulcerative keratitis (PUK) is an inflammatory condition of the peripheral cornea with hallmark features of epithelial defects and stromal destruction as a result of a complex interplay of factors including host autoimmunity and the peculiar anatomic and physiologic features of the peripheral cornea and environmental factors. PUK may be the result of local or systemic causes and infectious or noninfectious causes. Arriving at a specific etiological diagnosis requires a meticulous clinical workup that may include a battery of laboratory and radiological investigations. Management by a team of internists or rheumatologists and ophthalmologists and judicious use of immunosuppressive agents may yield favorable results minimizing adverse effects. We review current clinical knowledge on the diagnosis and management of PUK.     

Predictive factors for response to medical therapy in bacterial ulcerative keratitis

Background: Fifty-four consecutive cases of culture-positive bacterial ulcerative keratitis presenting at a major university hospital were reviewed to identify factors predictive of response to medical therapy for bacterial ulcerative keratitis (BUK). Methods: Eleven patients (20%) failed medical therapy (defined as the need for surgical intervention or cyanoacrylate gluing). Using multivariate logistic regression, the following variables were evaluated: (1) predisposing ocular factors (e.g., contact lens wear), (2) pre-existing ocular diseases, (3) ulcer size, and (4) the number of topical ocular medications used at the time of presentation. Results: We noted certain factors to be potentially predictive of medical therapy outcome. The average size of the ulcer at the time of presentation was 4.4±2.4 mm in the failure group but only 2.5±1.9 mm for the success group (P=0.027). In addition, patients in the medical failure group used more topical ocular medications at the time of presentation (P=0.0075). Further analysis of the individual topical ocular medications revealed that the use of corticosteroids was higher in the failure group (56% vs 12%, P=0.0005 by Fisher's exact test). Other factors such as patient age, the type of organism(s), and the time elapsed between the onset of symptoms and the beginning of definitive therapy were not statistically significant. Conclusion: In this population, ulcer size at the onset of antibacterial treatment and the use of certain ocular medications, specifically corticosteroids, were significant predictive factors for failure of medical therapy for BUK.     

Vasculitic peripheral ulcerative keratitis.

The onset of peripheral ulcerative keratitis in the course of a connective tissue disorder, such as rheumatoid arthritis, relapsing polychondritis, or systemic lupus erythematosus, may reflect the presence of potentially lethal systemic vasculitis. Moreover, peripheral ulcerative keratitis may be the first sign of systemic necrotizing vasculitis in patients with Wegener's granulomatosis, polyarteritis nodosa, microscopic polyangiitis, or Churg-Strauss syndrome. Although the exact pathogenesis of this severe corneal inflammation and destruction is not well understood, evidence points to a dysfunction in immunoregulation with immune complexes formed in response to autoantigens or to some unknown microbial antigen depositing in scleral and limbal vessels. These events lead to changes that are mainly responsible for the resulting tissue damage. In pauci-immune vasculitides positive for antineutrophil cytoplasmic antibodies, cell-mediated cytotoxicity may play an important role in the pathogenesis of peripheral ulcerative keratitis. Untreated systemic conditions such as those mentioned above may carry a grave prognosis for the eye and may also be life-threatening. Immunosuppressive therapy with corticosteroids and cytotoxic agents is, we believe, mandatory in the treatment of these multisystem disorders associated with vasculitic peripheral ulcerative keratitis.     

HLA-DR alleles and sterile ulcerative keratitis.

Human leukocyte antigen-DR typing was performed on 18 unrelated white patients with sterile ulcerative keratitis (SUK) to determine whether these patients share common immunogenetic susceptibility genes. There was no statistically significant increase in any DR allele among the entire group of SUK patients. There was a trend in the frequency of DR1 in the rheumatoid arthritis (RA) patients (5 of 8, 63%) versus the non-RA patients (1 of 10, 10%), which was not statistically significant, possibly due to the small number of patients in the study. Screening patients with RA without known SUK from our RA register revealed one DR1-positive patient with an inactive peripheral marginal melt. These findings suggest a possible relationship between DR1 and RA sterile corneal melting, which will need to be confirmed with a larger study.     

Herpes simplex keratitis misdiagnosed as rheumatoid arthritis-related peripheral ulcerative keratitis

PURPOSE: To report 2 cases of herpes simplex keratitis misdiagnosed as rheumatoid arthritis (RA)-related peripheral ulcerative keratitis (PUK), where isolation of the herpes simplex virus (HSV) led to a complete modification in management. METHODS: This is a case report. RESULTS: Two patients with RA presented with painful red right eyes. Ocular examination in both revealed an ulcer involving the peripheral cornea. The adjacent conjunctiva was infected, and the underlying sclera appeared inflamed. A diagnosis of corneal PUK secondary to RA was therefore made. The first patient had corneal scrapes taken for routine microbiological examination, which included polymerase chain reaction (PCR) for HSV. In the second patient, despite systemic immunosuppressive therapy, the ulcer progressed to involve deeper stroma and more central cornea. The conjunctiva adjacent to the ulcer was resected, and healthy conjunctival tissue was mobilized to cover the peripheral corneal ulcer. Resected conjunctival and corneal tissue was histopathologically assessed. In the first patient, PCR for HSV yielded a positive result. This prompted treatment with immediate systemic and topical acyclovir. The ulcer responded well to treatment. In the second patient, histopathological assessment and electron microscopy identified HSV. Treatment with topical trifluorothymidine and steroids was started, and a good recovery was made. CONCLUSIONS: Treatment of PUK is with systemic immunosuppressive therapy, and such therapies have serious side effects. PUK may have an occult cause in RA, and a search for a secondary agent may be beneficial. In particular, occult HSV infection must be ruled out before commencing immunosuppressive therapy.     

Peripheral ulcerative keratitis in a child

Peripheral ulcerative keratitis is a destructive process involving perilimbal corneal inflammation and an overlying epithelial defect. It can be a manifestation of systemic autoimmune diseases or can be secondary to an infectious process. We present a case of a 7-year-old girl with peripheral ulcerative keratitis of unknown etiology. To the best of our knowledge, this is the first such case reported in a child.     

Tectonic keratoplasty for peripheral ulcerative keratitis

Peripheral ulcerative keratitis (PUK) is a destructive, inflammatory process that can lead to corneal perforation and visual loss. Successful control of PUK has been reported with conjunctival resection, cyanoacrylate adhesive, and systemic immunosuppression. Cases with impending or actual corneal perforation may require more extensive surgery, including lamellar or penetrating keratoplasty, to maintain the integrity of the globe. We report on 17 eyes of 14 patients with PUK that required tectonic keratoplasty because of progressive ulceration. Surgery with concomitant immunosuppression preserved the eyes in all but two cases, and 8 of 17 eyes maintained or improved preoperative visual acuity. Six eyes had final visual acuities of 20/200 or better. This therapeutic strategy can preserve eyes that might otherwise be lost to progressive inflammation.     

Differentiation of etiologic agents of bacterial keratitis from presentation characteristics

Presenting characteristics of bacterial corneal ulcers may suggest particular causative organisms, helping to guide treatment decisions before cultures become available. In this study, we analyze the association between presentation demographic and clinical characteristics, using data collected as part of a randomized, controlled clinical trial. Data for this study were collected as part of the Steroids for Corneal Ulcers Trial, a randomized, placebo-controlled, double-masked trial. All patients had a culture-proven bacterial corneal ulcer. Patient history, clinical examination, and photography were performed in a standardized fashion at enrollment. Analysis of variance or Fisher’s exact test was used to compare characteristics by organism. Univariate logistic regression was used to analyze predictors of the most common organisms. Five hundred patients were enrolled in the trial, of whom 488 were included in this analysis. The most common organism was Streptococcus pneumoniae (N?=?248, 51?%) followed by Pseudomonas aeruginosa (N?=?110, 23?%). Compared to other organisms, P. aeruginosa was significantly associated with a larger baseline infiltrate/scar size [odds ratio (OR) 1.6, 95?% confidence interval (CI) 1.4–1.8] and deeper infiltrate (OR 2.4, 95?% CI 1.5–3.8). S. pneumoniae was significantly associated with a smaller baseline infiltrate/scar size (OR 0.8, 95?% CI 0.7–0.9) and dacryocystitis (OR 7.3, 95?% CI 4.1–13.3). Nocardia spp. were significantly associated with longer duration of symptoms prior to presentation (OR 1.4, 95?% CI 1.2–1.6), more shallow infiltrate (OR 0.3, 95?% CI 0.2–0.5), and better baseline visual acuity (OR 0.4, 95?% CI 0.2–0.65). Staphylococcus spp. were less likely to be central in location (OR 0.16, 95?% CI 0.08–0.3). Baseline characteristics of bacterial ulcers may suggest the likely etiology and guide early management.     

风湿病相关的边缘性角膜溃疡

边缘性角膜溃疡是指近角膜缘处角膜基质的半月形破坏性病变,伴随角膜上皮缺损、基质变性,以及基质炎性细胞浸润。风湿病常累及眼部,类风湿关节炎、Wegener’s肉芽肿、结节性多动脉炎、复发性多软骨炎、系统性红斑狼疮等可发生边缘性角膜溃疡。边缘性角膜溃疡可能是系统性血管炎的首发表现,也可能预示着某些风湿病进入了严重的血管炎阶段。眼科医师了解这些风湿病的全身及眼部表现,做出正确及时的诊断,并协同风湿科医师进行全身性治疗,对于挽救患者的生命和眼睛都是非常重要的。就边缘性角膜溃疡的病因、临床表现及治疗的研究进展进行综述。     

Peripheral ulcerative keratitis: Our challenging experience

A 52 year old male presented with peripheral ulcerative keratitis in the right eye. Patient’s history included retinitis pigmentosa, pseudophakia (right eye), cataract (left eye), bilateral partial deafness, ischemic heart disease, hypertension, type 1 diabetes mellitus, depression, hyperparathyroidism, hypertriglycemia and renal failure. The patient was on weekly hemodialysis. The peripheral corneal ulceration remained stable until he developed sudden and rapid thinning after eight months of regular follow up and management.Laboratory investigations including immunological studies were negative and we had to rely on treatment based on clinical signs, including the visual acuity, size, depth and staining of the ulcer and perilimbal, episcleral, scleral, corneal and anterior chamber reactions. The patient was treated with medical and conservative approaches and the eye was protected with a plastic shield to avoid injury. Despite our efforts, the patient perforated his eye due to a trivial trauma during sleep. He was managed successfully with cyanoacrylate glue and a bandage contact lens. The anterior chamber reformed after the perforation was sealed and the patient is on a regular follow up with a multidisciplinary approach.