Corneal nerve alterations in acute Acanthamoeba and fungal keratitis: an in vivo confocal microscopy study

Kurbanyan, Kristina; Hoesl, L. M.; Schrems, W.; Hamrah, Pedram

doi:10.1038/eye.2011.270

Cited by 51 publications

(48 citation statements)

References 14 publications

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“…The degree of sensitivity loss correlates with the severity of clinical disease. The loss of sensitivity in corneas of patients with HSK is thought to be irreversible (12) and associated with loss of nerve fibers extending from the corneal stroma into the epithelium (13,14). Nerve damage in corneas with HSK is assumed to be related to HSV-1 neurotropism, but it is unclear if damage is directly mediated by HSV-1 infection or is immunologically mediated.…”

mentioning

confidence: 99%

Reversible Nerve Damage and Corneal Pathology in Murine Herpes Simplex Stromal Keratitis

Yun

Rowe

Lathrop

et al. 2014

J Virol

108

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Herpes simplex virus type 1 (HSV-1) shedding from sensory neurons can trigger recurrent bouts of herpes stromal keratitis (HSK), an inflammatory response that leads to progressive corneal scarring and blindness. A mouse model of HSK is often used to delineate immunopathogenic mechanisms and bears many of the characteristics of human disease, but it tends to be more chronic and severe than human HSK. Loss of blink reflex (BR) in human HSK is common and due to a dramatic retraction of corneal sensory nerve termini in the epithelium and the nerve plexus at the epithelial/stromal interface. However, the relationship between loss of BR due to nerve damage and corneal pathology associated with HSK remains largely unexplored. Here, we show a similar retraction of corneal nerves in mice with HSK. Indeed, we show that much of the HSK-associated corneal inflammation in mice is actually attributable to damage to the corneal nerves and accompanying loss of BR and can be prevented or ameliorated by tarsorrhaphy (suturing eyelids closed), a clinical procedure commonly used to prevent corneal exposure and desiccation. In addition, we show that HSK-associated nerve retraction, loss of BR, and severe pathology all are reversible and regulated by CD4 ؉ T cells. Thus, defining immunopathogenic mechanisms of HSK in the mouse model will necessitate distinguishing mechanisms associated with the immunopathologic response to the virus from those associated with loss of corneal sensation. Based on our findings, investigation of a possible contribution of nerve damage and BR loss to human HSK also appears warranted. IMPORTANCEHSK in humans is a potentially blinding disease characterized by recurrent inflammation and progressive scarring triggered by viral release from corneal nerves. Corneal nerve damage is a known component of HSK, but the causes and consequences of HSK-associated nerve damage remain obscure. We show that desiccation of the corneal surface due to nerve damage and associated loss of BR severely exacerbates and prolongs inflammation-induced pathology in mice. Preventing corneal desiccation results in a milder and more transient HSK with variable scarring that mirrors HSK seen in most humans. We further show that nerve damage is reversible and regulated by CD4 ؉ T cells. Thus, we provide a mouse model that more closely resembles typical human HSK and suggest nerve damage is an important but largely overlooked factor in human disease.

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mentioning

confidence: 99%

Reversible Nerve Damage and Corneal Pathology in Murine Herpes Simplex Stromal Keratitis

Yun

Rowe

Lathrop

et al. 2014

J Virol

108

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“…It has also been found that corneal sensation may be decreased after fungal infection, supported by in vivo confocal microscopy showing decreased corneal nerve length as well as nerve counts [38].…”

Section: Clinical Outcomesmentioning

confidence: 80%

Fungal Keratitis: Update for 2014

Stone

Tan

2014

Curr Ophthalmol Rep

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Fungal keratitis is a challenging problem worldwide, and many obstacles remain to the effective prevention, diagnosis, and therapy of this vision-threatening condition. Recent research has highlighted progress in each of these facets of the clinical approach to keratomycosis. Increased awareness of contact lens-associated fungal keratitis has prompted regulators to pay greater attention to testing of contact lens solutions under realworld conditions. Related research has also delved into the mechanisms of fungal biofilm formation and related therapeutic targets. Advances in polymerase chain reaction methodologies promise to increase the rapidity and accuracy of diagnosis, thereby decreasing the delay in instituting appropriate therapy. Antifungal pharmacologic agents remain the first line of therapy, with the newer azole antifungal voriconazole being utilized in innovative ways, such as via intrastromal injection. Large prospective studies such as the Mycotic Ulcer Treatment Trial have helped delineate optimal treatment algorithms, and variations in surgical techniques and postoperative regimens continue to be refined. Natamycin may still be more effective than other recently utilized antifungals for the treatment of Fusarium infections, but treatment failure is still a concern. Post-keratoplasty immunosuppression may benefit from the use of topical calcineurin inhibitors such as cyclosporine and tacrolimus, given their intrinsic antifungal properties. It can be argued that the prevention, diagnosis, and treatment of fungal keratitis lag behind the state of the art for bacterial keratitis, but dramatic improvements are undoubtedly on the horizon.

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“…[15][16][17][18] In this study, high resolution laser IVCM was used to diagnose different kinds of concealed corneal foreign bodies. Results showed that glass corneal foreign bodies were more highly reflective than other foreign bodies and had a knife-edged appearance.…”

Section: Discussionmentioning

confidence: 99%

The role of in vivo confocal microscopy in the diagnosis of hidden corneal foreign bodies

et al. 2013

J Int Med Res

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Objective: To investigate in vivo confocal microscopy (IVCM) to diagnose hidden corneal foreign bodies. Methods: Male Kunming mice (n ¼ 25; 12 weeks old) were anaesthetized prior to the insertion of five different materials (spiny wood, rusty iron, sharp stone, sharp glass fragment and human hair fragment) into the cornea by different traumatic processes. A separate mouse was used for each corneal foreign body. The corneas of the mice were scanned 24 h later by a laser scanning IVCM to establish the characteristics (shape, reflectivity and depth in the cornea) of each foreign body. These findings were used to help screen and identify corneal foreign bodies in patients. Corneal smears and scraping cultures were performed in cases of probable corneal infection. Results: Animal models for the five different foreign particles were established successfully, with each showing distinctive characteristics. These animal results were used to diagnose 41 patients with suspected corneal foreign bodies who were negative by slit lamp examination, but positive by IVCM (observational case series). The most prevalent type of hidden foreign body was plant material (51.2%), followed by metal (29.3%). Ten patients with corneal foreign bodies developed fungal keratitis, found using IVCM. Conclusions: Laser IVCM is an effective and reliable tool for the diagnosis of hidden corneal foreign bodies.

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Corneal nerve alterations in acute Acanthamoeba and fungal keratitis: an in vivo confocal microscopy study

Cited by 51 publications

References 14 publications

Reversible Nerve Damage and Corneal Pathology in Murine Herpes Simplex Stromal Keratitis

Reversible Nerve Damage and Corneal Pathology in Murine Herpes Simplex Stromal Keratitis

Fungal Keratitis: Update for 2014

The role of in vivo confocal microscopy in the diagnosis of hidden corneal foreign bodies

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