Selective Changes in Human Corneal Sensation Associated with Herpes Simplex Virus Keratitis

Gallar, Juana; Tervo, Timo; Neira, Waldir; Holopainen, Juha M.; Lamberg, Marko; Miñana, Fernando; Acosta, M. Carmen; Belmonte, Carlos

doi:10.1167/iovs.10-5225

Cited by 62 publications

(55 citation statements)

References 38 publications

(44 reference statements)

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“…The chronicity of this situation, common to other ocular surface diseases [18][19][20][21][22] , has been described as one of the causes of corneal nerve injury 2 . In any case, multifactorial origin of corneal hypoesthesia in eyes with pterygium should not be dismissed.…”

Section: Discussionmentioning

confidence: 99%

Determining Factors for Fast Corneal Sensitivity Recovery After Pterygium Excision

Julio

Campos

Pujol

et al. 2016

Cornea

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Purpose: To establish determining factors for fast corneal sensitivity (CS) recovery after pterygium excision.Methods: Thirty-two eyes of 14 males and 18 females with primary nasal pterygium were recruited. Differences in CS (in the four quadrants and the center using Cochet-Bonnet esthesiometer), pterygium corneal area (PCA), tear osmolarity, tear break up time, Schirmer test, and ocular symptoms were analyzed before and 1 month after lesion excision. The relationship between CS recovery (difference between the two time points; CS1-CS0) and the other features was assessed.Results: All the studied locations exhibited normal (6 cm) or near normal mean CS at the 2 time points, except tendency for moderate hypoesthesia in nasal CS0 (median 4.5; range: 1.5 -6.0 cm). Point by point comparison revealed significant postoperative improve in nasal location (p=0.008; Wilcoxon rang test) with normal values in 17 eyes (53%) and a median CS1= 5.0 cm (2.5 -5.5 cm) in 15 eyes with no complete recovery. No significant correlation was found between CS0 and the studied variables and CS1 was only significantly correlated with PCA (rho: -0.441; p<0.05). CS recovery also showed significant correlation with PCA (rho= -0.516; p<0.01). Conclusions:Corneal sensitivity recovery after pterygium excision showed important variability and the only studied factor that seems to be determinant could be PCA. It would be advisable to operate while lesion is relatively small, with lower surgical injury, and faster and complete recovery, thus protecting ocular surface homeostasis.3

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Section: Discussionmentioning

confidence: 99%

Determining Factors for Fast Corneal Sensitivity Recovery After Pterygium Excision

Julio

Campos

Pujol

et al. 2016

Cornea

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“…Reduced corneal sensation (hypoesthesia), often assessed by a loss of corneal blink reflex (BR), is another hallmark of HSK in both humans and mice (9)(10)(11). Decreased corneal sensitivity plays an important role both in the diagnosis and prognosis of all types of herpetic keratitis (12).…”

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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“…Therefore, we were forced to consider the possible use of lytic granules in controlling HSV-1 latency. Indeed, patients with recurrent herpes keratitis tend to lose some sensation in their corneas over time (Gallar et al 2010). However, it is unclear if this loss of sensation is due to neuronal death resulting from HSV-1 replication during a reactivation event or neuronal death due to CD8 + T cell killing of neurons in combating reactivation.…”

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confidence: 99%

CD8+ T cells patrol HSV-1-infected trigeminal ganglia and prevent viral reactivation

Leger

Hendricks

2011

J. Neurovirol.

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A hallmark of herpes viruses is their capacity to cause recurrent disease. Recurrences of herpes simplex virus (HSV)-1 disease do not result from reinfection from external sources, but rather from reactivation of virus that is maintained in a latent state in sensory neurons and periodically reactivates from latency to cause recurrent disease. Recent findings implicate HSV-specific CD8(+) T cells in immune surveillance of HSV-1 latently infected sensory neurons in trigeminal ganglia (TG) and inhibition of HSV-1 reactivation from latency. This review summarizes recent findings regarding the characteristics of the TG-resident CD8(+) T cell population and certain unique obstacles that might complicate the development of therapeutic vaccines.

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Selective Changes in Human Corneal Sensation Associated with Herpes Simplex Virus Keratitis

Cited by 62 publications

References 38 publications

Determining Factors for Fast Corneal Sensitivity Recovery After Pterygium Excision

Determining Factors for Fast Corneal Sensitivity Recovery After Pterygium Excision

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

CD8+ T cells patrol HSV-1-infected trigeminal ganglia and prevent viral reactivation

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