Diagnosis Of Herpes Simplex Keratitis Research Articles

Diagnostic performance of real-time quantitative PCR in tear samples in various subtypes of herpes simplex keratitis.

Diagnosis of herpes simplex keratitis (HSK) is mostly based on clinical findings, yet biological confirmation supports management of challenging cases. This study evaluated the place of real-time quantitative PCR (RT-qPCR) on tear samplings in the management of HSK. Clinical records of patients who underwent tear sampling tested by RT-qPCR for herpes simplex virus type 1 for an acute episode of corneal inflammation or defect between January 2013 and December 2021 were retrospectively reviewed, and results were compared to clinical diagnosis (i.e., HSK or not) based on biomicroscopic findings and medical history. Of 465 tested tear samples from 364 patients, a clinical diagnosis of active (ongoing) HSK was recorded in 240 cases, among which 76 were RT-qPCR positive (global sensitivity of 31.6%, specificity of 99.5%). Sensitivity of RT-qPCR was higher in epithelial (97.4%) and stromal keratitis with ulceration (48.7%), compared to other types of HSK (23.5% in keratouveitis, 13.6% in endotheliitis, 11.1% in postherpetic neurotrophic keratopathy, and 8.1% in stromal keratitis without ulceration). The highest viral loads were detected from epithelial and stromal keratitis with ulceration, while in HSK with no epithelial involvement, the viral load detected was 196-fold lower, on average. The proportion of clinically characterized HSK patients with negative tear samples was higher in patients receiving antiviral treatment (P < 0.0001). RT-qPCR, performed on tear samples, can help in confirming diagnosis in case of presumed HSK, including clinical forms with no obvious epithelial involvement. The sensitivity of tear sampling is much higher whenever epithelial keratitis is present.

Optical Diagnostics in Herpetic Keratitis

One of the leading global causes of vision impairment due to anterior segment disease is herpes simplex keratitis (HSK). The routine clinical method in the diagnosis of HSK is examination of the eye using slit lamp biomicroscopy; nevertheless, this is a subjective examination and can potentially lead to an erroneous diagnosis. Optical devices such as in vivo confocal microscopy and anterior segment optical coherence tomography are among the additional diagnostic tools that provide a valuable resource in the diagnosis and management of the condition. In research settings, these technologies have already enhanced our understanding of the microscopic causes of numerous common in vivo observations. This review aims to highlight the multiple emerging clinical and research applications for optical imaging devices in HSK.

Herpetic endotheliitis following an uncomplicated cataract surgery

Introduction: Herpetic endotheliitis after cataract surgery is a rare complication, and it is more likely linked with previous ocular herpetic infection. Case Report: In the current case, the patient of this study is a 66-year-old woman without a personal history of herpes simplex keratitis (HSK) who underwent an uneventful phacoemulsification in her left eye. For the next two weeks, corneal endotheliitis appeared in the same eye, and then the initial diagnosis of HSK was made clinically. The patient was treated with systemic and topical antiviral therapy associated with an intensive topical corticosteroid. In four weeks, a complete resolution of the corneal edema was noticed and the visual acuity was improved (6/9). Conclusion: The occurrence of corneal edema after cataract surgery could reveal a herpetic endotheliitis, although early diagnosis and early treatment with strict monitoring are the keys to successful control of this affection.

Herpes simplex Keratitis Mimicking Acute Corneal Hydrops

Purpose: The purpose of this paper is to present a case of a Herpes simplex keratitis presenting as a case of acute corneal hydrops. Methods: Case report. Results: A 57-year-old white woman presented with acute onset of pain, photophobia and decreased vision in the left eye. In the years prior, she had been under the care of her optometrist, who had previously diagnosed her with irregular astigmatism, for which she had been using rigid gas permeable contact lenses for vision correction. At the slit-lamp biomicroscope, the left eye was found to have marked corneal edema with central endothelial folds, as well as a round, paracentral area of stromal haze and opacity. The fellow eye was shown to have inferior areas of anterior stromal scarring. Corneal topography showed markedly irregular astigmatism, with inferior steepening bilaterally. These are findings that could also be seen in acute corneal hydrops. In this case, a diagnosis of Herpes Simplex keratitis was made, and patient showed marked improvement on oral valacyclovir. Conclusions: Herpes simplex keratitis can often be a diagnostic challenge, as it can present itself in various forms. We report a case of Herpes simplex keratitis mimicking acute corneal hydrops.

A Comparison of the Clinical and Molecular Diagnosis of Herpes Simplex Keratitis

Purpose: To compare the clinical and molecular diagnoses of Herpes Simplex Keratitis (HSK). Materials and Methods: Conjunctival swabs (after fluorescein and anaesthetic wash out) and detailed questionnaire data were obtained from 146 participants. Corneal rims and conjunctival epithelial cells were infected with Herpes Simplex Virus (HSV) type 1 or HSV2 and supernatant collected. HSV1; HSV2; Varicella Zoster Virus (VZV) and Adenovirus (ADV) DNA was assessed using two real time Polymerase Chain Reaction (PCR) methods. Results: Of the 146 participants recruited, 54 were clinically diagnosed with typical epithelial lesions and 38 with atypical epithelial lesions, 17 with old inactive HSK and 37 healthy volunteers. HSV1 DNA was detected in 28 (30%) of the 92 participants with clinically suspect HSK. Patients who presented with typical epithelial lesions had a higher positive rate (46%) than those who presented with atypical type lesions (8%), when using primers against the Glycoprotein (Gp) G region of the virus. When the same samples were retested with primers against the GpB region, the positive rate for the typical and atypical cases increased to 52% and 11% respectively. Antiviral use at the time of sampling reduced the rate of PCR positivity by 20% (p in vitro control investigations of HSV1 and 2 infected corneal rims and conjunctival epithelial cells were 100% positive for infected and 100% negative for uninfected samples when assessed using both PCR methods. Conclusions: Clinical diagnosis of typical HSK is not always confirmed by PCR. Concomitant use of an antiviral reduces levels of PCR positivity. Given this and the findings that other ocular surface pathogens may mimic HSK pathology, and that choice of gene amplification region can also affect accurate detection of HSV1 by PCR, we propose the use of a multiplex assay. This would perform PCR using primers spanning a number of different regions within one gene and would also target a number of different viral genes to ensure potentially different HSV1 viral strains or other viruses do not affect the test and lead to disagreements between the clinical and molecular diagnosis of HSK. From these findings, this paper proposes a clinical supportive algorithmic guide to manage such disagreements.

Comparison of the sensitivity of a 24 h-shell vial assay, and conventional tube culture, in the isolation of Herpes simplex virus - 1 from corneal scrapings.

BackgroundHerpes simplex keratitis is a sight threatening ocular infection. A rapid and specific diagnosis is essential for the institution of specific antiviral therapy and to avoid complications that can arise from misdiagnosis and inappropriate treatment. Though a variety of techniques are available, isolation of Herpes simplex virus 1 (HSV-1) in culture provides the most reliable and specific method, and is considered as the gold standard in laboratory diagnosis of herpes simplex keratitis. We report a comparative study of the sensitivity of a 24 h-shell vial assay and conventional tube culture in the isolation of HSV-1 from corneal scrapings.MethodsA total of 74 corneal scrapings obtained from 74 patients with a clinical suspicion of herpes simplex keratitis submitted for the isolation of HSV-1, were simultaneously inoculated into shell vial and tube cultures employing the vero cell line. Shell vial and tube cultures were terminated at 24 h and fifth day respectively. Isolation of HSV-1 was confirmed employing an indirect immunofluorescence assay.ResultsHSV-1 was isolated from 24/74 (32.4%) specimens employing both the methods. Sensitivity of both the techniques were found to be similar (20/24, 83.3%) (P = 1.0).ConclusionA 24 h-shell vial assay is a rapid alternative technique in comparison to the time consuming conventional tube cultures for the isolation of HSV-1, especially from corneal scrapings for the laboratory diagnosis of herpes simplex keratitis.

Herpes simplex virus bullous keratitis misdiagnosed as a case of pseudophakic bullous keratopathy with secondary glaucoma: an unusual presentation

PurposeTo report an unusual case of herpetic bullous keratitis misdiagnosed as a case of pseudophakic bullous keratopathy with secondary glaucoma.ResultsA retrospective analysis of the case record of a 60-year-old man who had earlier undergone bilateral cataract surgery, was done. He presented with a complaint of decrease in vision in the right eye of 20 days duration. On examination, cornea showed epithelial bullae all over the surface with stromal and epithelial edema. Intraocular pressure was 30 mm of Hg in RE. He was treated with anti-glaucoma medications. Two dendritic lesions were seen in the cornea during a subsequent visit four days later. Virological investigations confirmed a diagnosis of Herpes simplex keratitis. He was treated with topical acyclovir.ConclusionsThis case highlights the fact that herpes simplex keratitis can present initially as a more diffuse corneal stromal and epithelial edema with epithelial bullae mimicking bullous keratopathy. Herpetic bullous keratitis, although unusual, should be considered in the differential diagnosis under such circumstances.

Tear secretory IgA: evaluation of usefulness as a diagnostic marker in herpetic keratitis

In a South Indian study, an `in-house' enzyme-linked immunosorbent assay (ELISA) was developed to evaluate the potential of herpes simplex virus (HSV)-specific tear secretory IgA (sIgA) in the diagnosis of herpes simplex keratitis (HSK). The presence of HSV-specific tear sIgA was found to be diagnostic in 20.28% of cases. The usefulness of the sIgA ELISA system was evaluated against HSV isolation, which is the `gold standard' and HSV antigen detection, a more sensitive, commonly employed method. Analysis of HSV-specific IgG and IgM results showed their failure as reliable indicators of active or ongoing infection. Comparison of sIgA ELISA with culture as `gold standard' showed its sensitivity, specificity, and positive and negative predictive values to be 60% (95% CI 36.4-80), 93.2% (95% CI 86.7-96.8), 60% (95% CI 36.4-80), and 93.2% (95% CI 86.7-96.8), respectively. This study is the first report on the complete evaluation of the usefulness of tear anti-HSV sIgA in the laboratory diagnosis of HSK, taking into account both epithelial and stromal keratitis cases.

Two laboratory methods for diagnosis of herpes simplex keratitis.

Two techniques are described which enable a rapid diagnosis of herpes simplex keratitis to be made. The tests, antibody/antigen reactions, were shown to be accurate and sensitive in the 119 patients examined. A result is available within four hours with the indirect peroxidase-antiperoxidase method and within one hour with the direct method. The techniques are relatively inexpensive, though labour intensive. Negative reactions were found in treated cases and in those with some delay in the histochemical staining.

Chronic Keratitis Caused by Mycobacterium gordonae

We treated a patient with chronic keratitis caused by Mycobacterium gordonae, a slow-growing, atypical mycobacterium not previously reported as a cause of corneal infection. The patient was a 34-year-old man who was hit in the eye with some vegetable matter while gardening. Initially, the patient was treated for a presumptive diagnosis of herpes simplex keratitis. Because of progression of the keratitis, a lamellar corneal biopsy was performed 3 1/2 years later and the definitive diagnosis was made. Subsequently, a penetrating keratoplasty was performed and the patient's condition then remained stable. The diagnosis of atypical mycobacterium should be considered in a patient with an indolent corneal ulcer. Lamellar corneal biopsy may disclose the pathogen when the infection is deep, chronic, or partially treated.

Rapid Diagnosis of Acanthamoeba Keratitis From Corneal Scrapings Using Indirect Fluorescent Antibody Staining

Two soft contact lens wearers using a homemade saline solution developed corneal stromal inflammation and epithelial ulceration and were both treated for months with a presumptive diagnosis of herpes simplex keratitis. Subsequently, corneal scrapings revealed refractile, cystic structures consistent with the appearance of Acanthamoeba. This was rapidly confirmed by indirect fluorescent antibody studies, and Acanthamoeba castellani was later identified by growth in culture in both cases. Acanthamoeba is being reported with increasing frequency as a pathogen responsible for chronic stromal keratitis and ulceration in contact lens wearers. Since specific therapy is required to control this organism, rapid diagnosis is essential. Indirect fluorescent antibody staining of corneal scrapings provides a simple means of accomplishing this goal with a high degree of accuracy.

A modified immunoperoxidase method for rapid diagnosis of herpes simplex I keratitis.

To study the possibility of establishing a rapid diagnosis of herpes simplex keratitis, corneas of 10 rabbits, a total of 20 eyes, were inoculated with herpes simplex virus (HSV), type I, strain PH. Epithelial keratitis developed within three days of inoculation in all the animals used. Scraping of infected corneas were smeared and examined, using a modified indirect immunoperoxidase technic. One hundred percent of the smears prepared from these corneas demonstrated positive cells. Negative findings in corneas inoculated with adenovirus 19 suggest the specificity of the reaction. To test the possibility of blockage of staining by the presumed development of circulating endogenous anti-HSV I antibodies, the corneas of eight consecutive patients who presented to the Albany Medical Center Hospital with known recurrent dendritic keratitis also were scraped and stained, using a similar procedure. Positive cells present in each of these scrapings suggest against the blocking of this immunoperoxidase method by the development of circulating anti-HSV antibodies.

Application of immunoperoxidase staining in the cytodiagnosis of herpes simplex keratitis

In corneal scraping smears from 13 patients with clinically suspected herpes simplex keratitis (HSK), HSK is demonstrated by means of peroxidase-antiperoxidase (PAP) technique with antisera to herpes simplex virus (HSV) in Papanicolaou-destained cellular samples. The staining for HSV antigen was present in seven cases of corneal scraping smears with superficial keratitis (dendritic and geographic ulcers) while six cases of stromal keratitis (deep keratitis) failed to show HSV antigen except in one case. Specific antigen for HSV was predominantly present in the cytoplasm rather than in the nucleus. Immunoreactions were negative with HSV antisera in patients with other infections and in those in a normal control group. Using the PAP technique, detection of HSV antigen in corneal scraping smears was of great value in the diagnosis of HSK, especially in cases of superficial keratitis.

Pseudodendritic Keratitis and Systemic Tyrosinemia

Three children (6 eyes) with systemic tyrosinemia who presented with a diagnosis of herpes simplex keratitis are described. Two of the patients underwent extensive treatment for herpes simplex keratitis until their defects in tyrosine metabolism were discovered. All three children responded favorably to a low-tyrosine diet. These cases illustrate the typical corneal findings of the Richner-Hanhart syndrome (pseudodendritic keratitis, hyperkeratotic skin lesions of the palms and sole without mental retardation). The findings in these three patients were similar to those cases previously reported in the literature except none had mental retardation. The ophthalmologist confronted with a young child with bilateral dendritiform keratitis should request evaluation of the serum tyrosine levels.