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Herpes Simplex epithelial keratitis associated with daily disposable contact lens wear
Contact Lens & Anterior Eye 37 (2014) 228–229
Contents lists available at ScienceDirect
Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae
Case report
Herpes Simplex epithelial keratitis associated with daily disposable contact lens wear Ahmed Hamroush ∗ , James Welch Tennent Institute of Ophthalmology, Gartnavel General Hospital, United Kingdom
a r t i c l e
i n f o
Article history: Received 17 September 2012 Received in revised form 29 September 2013 Accepted 20 November 2013 Keywords: Herpes Simplex keratitis Contact lens Immune response at the ocular surface
a b s t r a c t Purpose: To report a case of epithelial Herpes Simplex keratitis in a patient wearing daily disposable contact lenses. Method: Case report. Results: A 30-year-old female contact lens wearer presented to the emergency clinic with a painful, red left eye associated with an acute reduction of vision over 48 h. On examination, confluent dendritic ulcers were present on the cornea. Neither pertinent ocular nor medical history was obtained to explain such a dramatic clinical presentation. Conclusion: Contact lens wear was the only risk factor identified, perhaps resulting in deviation of the immune response at the ocular surface, with consequent extensive dendritic ulceration. © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction Herpes Simplex keratitis (HSK) is a major cause of visual morbidity worldwide. Replication of the virus within the corneal epithelium produces epithelial HSK, which not only causes acute symptoms but may also lead to stromal disease, resulting in permanent scarring and opacification [1]. The pathogenesis and severity of HSK is largely determined by the interaction between this doublestranded DNA virus and the host’s immune system; therefore any factor deviating the immune response at the ocular surface could influence the resulting clinical picture. A possible factor is soft contact lens wear, as it is known to have significant effects on many corneal structures [5]. 2. Case report A 30-year-old female presented to the emergency clinic with a two-day history of a painful left eye and associated reduction of vision. The patient had already attended her GP the previous day and had been commenced on Chloramphenicol 0.5% eye drops 2 hourly with no symptomatic improvement. She had worn daily disposable soft contact lenses successfully for many years. On questioning she denied sleeping, swimming or having showered whilst wearing her contact lenses. Neither pertinent ocular nor medical
∗ Corresponding author at: Tennent Institute of Ophthalmology, Gartnavel General Hospital, 1053 Great Western Road, Glasgow G12 0YN, United Kingdom. Tel.: +44 7999681508. E-mail address: [email protected] (A. Hamroush).
history was identified; specifically there was no history of atopy, ocular surface disease nor systemic immunosuppression, including pregnancy. She was not on any topical or systemic medications otherwise. Best corrected visual acuity was recorded as count fingers left eye and 6/5 right eye. On examination, the left eye demonstrated a mild diffuse conjunctival congestion, with multiple dendritic ulcers observed (Figs. 1 and 2). No stromal or endothelial activity was noted. Corneal sensation was reduced. No anterior chamber inflammation was present and intraocular pressure was within normal limits. Right eye examination was unremarkable. A clinical diagnosis of epithelial HSK was made. A corneal scrape for HSV and Acanthamoeba culture was performed. Diagnosis was subsequently confirmed by positive HSV Type 1 polymerase chain reaction. Aciclovir 0.3% eye ointment 5 times daily was instituted. At review, one week later, best corrected visual acuity had improved to 6/9 + 3 left eye, with resolution of all the dendritic ulcers; only subtle subepithelial corneal opacities remained. The treatment was discontinued forthwith and the patient received routine advice regarding contact lenses wear and the possibility of HSK recurrence. 3. Discussion Extensive dendritic ulceration is an unusual presentations of HSK in the absence of predisposing factors such as systemic immunodeficiency, topical steroid use [3] or atopy [4]. It has been reported that the use of different types of contact lenses affects corneal structures, including those involved in local ocular immunity [2]. Confocal microscopy has improved our
1367-0484/$ – see front matter © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clae.2013.11.007
A. Hamroush, J. Welch / Contact Lens & Anterior Eye 37 (2014) 228–229
Fig. 1. Multiple corneal dendritic ulcers in the left eye.
229
Langerhans cells form an essential part of the corneal immune surveillance system and are, responsible for the recognition, processing and presentation of antigens. After Langerhans cells recognize HSV as non-self, the antigen is processed and is transported to the cell surface by both class I and II major histocompatibility complex (MHC) molecules. This in turn activates T-cells which bind to the T-cell receptor on the MHC complex. These T cells then mature into effector cells, which are CD4+, if the MHC molecules presenting the antigen are class II, or CD8+, if the MHC is class I. The T cells either directly kill the virus (CD8+ cytotoxic cells) or secrete cytokines (CD4+ T helper cells) which attract other effector cells, predominantly macrophages, which are involved in the destruction of the virus [17,18]. Contact lens wear changes the density and distribution of Langerhans cells with the cornea compared to controls [19]. By compromising several facets of the immune defences at the ocular surface, contact lens wear may deviate the immune response to Herpes Simplex infection and directly influence the extent and natural history of the resultant keratitis as was demonstrated by our case. References
Fig. 2. Multiple dendritic ulcers in the same patient highlighted using a Cobalt Blue filter following instillation of 1% fluorescein.
understanding of the corneal changes that occur in response to contact lens wear [5]. Corneal nerves are important in the defence of the cornea as pain sensations result in the release of neuropeptides, specifically calcitonin gene related peptide and substance P. Both are released from the termini of corneal sensory neurons [6,7], and bind to human corneal epithelial cells, inducing interleukin (IL)-8 synthesis, resulting in neutrophil influx which contribute to HSV removal [8]. While some studies report quantitative changes in corneal nerves and reduction of total axon length of the subepithelial nerve plexus in soft lens wearers [9], others showed only qualitative changes with decreased corneal sensitivity in contact lens wearers compared to control subjects [10]. Epithelial cells themselves are capable of directly secreting cytokines to activate immune defences. IL-1 is stored within epithelial cells and then passively released when the cell membrane is ruptured due to infection or trauma [11]. This pro-inflammatory mediator attracts innate immune cells such as neutrophils to eradicate the virus. Use of contact lenses is found to increase the size of the superficial epithelial cells [12], with overall thinning of the epithelial layer [13]. Stromal keratocytes also have a defensive capacity during microbial invasion. Under the influence of IL-1 and tumour necrosis factor (TNF), keratocytes synthesize IL-6 and defensins [14]. IL6 interacts synergistically with IL-1 to attract inflammatory cells and the defensins have a broad spectrum of antimicrobial activity (bacteria, fungi, and viruses) and accelerate epithelial healing [15]. Studies using confocal microscopy report significant decrease in keratocyte numbers, both in the anterior and posterior stroma, compared to non-lens wearers [16].
[1] Wilhelmus KR, Coster DJ, Donovan HC, Falcon MG, Jones BR. Prognostic indicators of herpetic keratitis: analysis of a five-year observation period after corneal ulceration. Arch Ophthalmol 1981;99:1578–82. [2] Liesegang TJ. Physiologic changes of the cornea with contact lens wear. CLAO J 2002;28(January (1)):12–27. [3] Easty DL. Manifestations of immunodeficiency diseases in ophthalmology. Trans Ophthalmol Soc UK 1977;97:8–17. [4] Easty D, Entwistle C, Funk A, Witcher J. Herpes simplex keratitis and keratoconus in the atopic patient. A clinical and immunological study. Trans Ophthalmol Soc UK 1975;95:267–76. [5] Efron N. Contact lens-induced changes in the anterior eye as observed in vivo with the confocal microscope. Prog Retin Eye Res 2007;26:398–436. [6] Tran MT, Ritchie MH, Lausch RN, Oakes JE. Calcitonin gene-related peptide induces IL-8 synthesis in human corneal epithelial cells. J Immunol 2000;164:4307–12. [7] Tran MT, Lausch RN, Oakes JE. Substance P differentially stimulates IL-8 synthesis in human cornea epithelial cells. Invest Ophthalmol Vis Sci 2000;41:3871–7. [8] Thomas J, Gangappa S, Kanangat S, Rouse BT. On the essential involvement of neutrophils in the immunopathologic disease: herpetic stromal keratitis. J Immunol 1997;158:1383–91. [9] Bansal AK, Mustonen RK, McDonald MB. High resolution in vivo scanning confocal microscopy of the cornea in long term contact lens wear. Invest Ophthalmol Vis Sci 1997;38:S138. [10] Patel SV, McLaren JW, Hodge DO, Bourne WM. Confocal microscopy in vivo in corneas of long-term contact lens wearers. Invest Ophthalmol Vis Sci 2002;43:995–1003. [11] Niederkorn JY, Peeler JS, Mellon J. Phagocytosis of particulate antigens by corneal epithelial cells stimulates interleukin-1 secretion and migration of Langerhans cells into the central cornea. Reg Immunol 1989;2:83–90. [12] Ren DH, Petroll WM, Jester JV, Ho-Fan J, Cavanagh HD. The relationship between contact lens oxygen permeability and binding of Pseudomonas aeruginosa to human corneal epithelial cells after overnight and extended wear. CLAO J 1999;25:80–100 [Erratum 25, 175]. [13] Tsubota K, Yamada M. Corneal epithelial alterations induced by disposable contact-lens wear. Ophthalmology 1992;99:1193–6. [14] Cubitt CL, Lausch RN, Oakes JE. Differences in interleukin-6 gene expression between cultured human corneal epithelial cells and keratocytes. Invest Ophthalmol Vis Sci 1995;36:330–6. [15] Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, et al. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 1985;76:1427–35. [16] Weed KH, Macewen CJ, Cox A, McGhee CN. Quantitative analysis of corneal microstructure in keratoconus utilising in vivo confocal microscopy. Eye 2006, http://dx.doi.org/10.1038/sj.eye.6702286. [17] Gillette TE, Chandler JW, Greiner JV. Langerhans cells of the ocular surface. Ophthalmology 1982;89:700–11. [18] Jager MJ, Bradley D, Atherton S, Streilein JW. Presence of Langerhans cells in the central cornea linked to the development of ocular herpes in mice. Exp Eye Res 1992;54:835–41. [19] Zhivov A, Stave J, Vollmar B, Guthoff R. In vivo confocal microscopic evaluation of Langerhans cell density and distribution in the corneal epithelium of healthy volunteers and contact lens wearers. Cornea 2007;26(1):47–54.
Contents lists available at ScienceDirect
Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae
Case report
Herpes Simplex epithelial keratitis associated with daily disposable contact lens wear Ahmed Hamroush ∗ , James Welch Tennent Institute of Ophthalmology, Gartnavel General Hospital, United Kingdom
a r t i c l e
i n f o
Article history: Received 17 September 2012 Received in revised form 29 September 2013 Accepted 20 November 2013 Keywords: Herpes Simplex keratitis Contact lens Immune response at the ocular surface
a b s t r a c t Purpose: To report a case of epithelial Herpes Simplex keratitis in a patient wearing daily disposable contact lenses. Method: Case report. Results: A 30-year-old female contact lens wearer presented to the emergency clinic with a painful, red left eye associated with an acute reduction of vision over 48 h. On examination, confluent dendritic ulcers were present on the cornea. Neither pertinent ocular nor medical history was obtained to explain such a dramatic clinical presentation. Conclusion: Contact lens wear was the only risk factor identified, perhaps resulting in deviation of the immune response at the ocular surface, with consequent extensive dendritic ulceration. © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction Herpes Simplex keratitis (HSK) is a major cause of visual morbidity worldwide. Replication of the virus within the corneal epithelium produces epithelial HSK, which not only causes acute symptoms but may also lead to stromal disease, resulting in permanent scarring and opacification [1]. The pathogenesis and severity of HSK is largely determined by the interaction between this doublestranded DNA virus and the host’s immune system; therefore any factor deviating the immune response at the ocular surface could influence the resulting clinical picture. A possible factor is soft contact lens wear, as it is known to have significant effects on many corneal structures [5]. 2. Case report A 30-year-old female presented to the emergency clinic with a two-day history of a painful left eye and associated reduction of vision. The patient had already attended her GP the previous day and had been commenced on Chloramphenicol 0.5% eye drops 2 hourly with no symptomatic improvement. She had worn daily disposable soft contact lenses successfully for many years. On questioning she denied sleeping, swimming or having showered whilst wearing her contact lenses. Neither pertinent ocular nor medical
∗ Corresponding author at: Tennent Institute of Ophthalmology, Gartnavel General Hospital, 1053 Great Western Road, Glasgow G12 0YN, United Kingdom. Tel.: +44 7999681508. E-mail address: [email protected] (A. Hamroush).
history was identified; specifically there was no history of atopy, ocular surface disease nor systemic immunosuppression, including pregnancy. She was not on any topical or systemic medications otherwise. Best corrected visual acuity was recorded as count fingers left eye and 6/5 right eye. On examination, the left eye demonstrated a mild diffuse conjunctival congestion, with multiple dendritic ulcers observed (Figs. 1 and 2). No stromal or endothelial activity was noted. Corneal sensation was reduced. No anterior chamber inflammation was present and intraocular pressure was within normal limits. Right eye examination was unremarkable. A clinical diagnosis of epithelial HSK was made. A corneal scrape for HSV and Acanthamoeba culture was performed. Diagnosis was subsequently confirmed by positive HSV Type 1 polymerase chain reaction. Aciclovir 0.3% eye ointment 5 times daily was instituted. At review, one week later, best corrected visual acuity had improved to 6/9 + 3 left eye, with resolution of all the dendritic ulcers; only subtle subepithelial corneal opacities remained. The treatment was discontinued forthwith and the patient received routine advice regarding contact lenses wear and the possibility of HSK recurrence. 3. Discussion Extensive dendritic ulceration is an unusual presentations of HSK in the absence of predisposing factors such as systemic immunodeficiency, topical steroid use [3] or atopy [4]. It has been reported that the use of different types of contact lenses affects corneal structures, including those involved in local ocular immunity [2]. Confocal microscopy has improved our
1367-0484/$ – see front matter © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clae.2013.11.007
A. Hamroush, J. Welch / Contact Lens & Anterior Eye 37 (2014) 228–229
Fig. 1. Multiple corneal dendritic ulcers in the left eye.
229
Langerhans cells form an essential part of the corneal immune surveillance system and are, responsible for the recognition, processing and presentation of antigens. After Langerhans cells recognize HSV as non-self, the antigen is processed and is transported to the cell surface by both class I and II major histocompatibility complex (MHC) molecules. This in turn activates T-cells which bind to the T-cell receptor on the MHC complex. These T cells then mature into effector cells, which are CD4+, if the MHC molecules presenting the antigen are class II, or CD8+, if the MHC is class I. The T cells either directly kill the virus (CD8+ cytotoxic cells) or secrete cytokines (CD4+ T helper cells) which attract other effector cells, predominantly macrophages, which are involved in the destruction of the virus [17,18]. Contact lens wear changes the density and distribution of Langerhans cells with the cornea compared to controls [19]. By compromising several facets of the immune defences at the ocular surface, contact lens wear may deviate the immune response to Herpes Simplex infection and directly influence the extent and natural history of the resultant keratitis as was demonstrated by our case. References
Fig. 2. Multiple dendritic ulcers in the same patient highlighted using a Cobalt Blue filter following instillation of 1% fluorescein.
understanding of the corneal changes that occur in response to contact lens wear [5]. Corneal nerves are important in the defence of the cornea as pain sensations result in the release of neuropeptides, specifically calcitonin gene related peptide and substance P. Both are released from the termini of corneal sensory neurons [6,7], and bind to human corneal epithelial cells, inducing interleukin (IL)-8 synthesis, resulting in neutrophil influx which contribute to HSV removal [8]. While some studies report quantitative changes in corneal nerves and reduction of total axon length of the subepithelial nerve plexus in soft lens wearers [9], others showed only qualitative changes with decreased corneal sensitivity in contact lens wearers compared to control subjects [10]. Epithelial cells themselves are capable of directly secreting cytokines to activate immune defences. IL-1 is stored within epithelial cells and then passively released when the cell membrane is ruptured due to infection or trauma [11]. This pro-inflammatory mediator attracts innate immune cells such as neutrophils to eradicate the virus. Use of contact lenses is found to increase the size of the superficial epithelial cells [12], with overall thinning of the epithelial layer [13]. Stromal keratocytes also have a defensive capacity during microbial invasion. Under the influence of IL-1 and tumour necrosis factor (TNF), keratocytes synthesize IL-6 and defensins [14]. IL6 interacts synergistically with IL-1 to attract inflammatory cells and the defensins have a broad spectrum of antimicrobial activity (bacteria, fungi, and viruses) and accelerate epithelial healing [15]. Studies using confocal microscopy report significant decrease in keratocyte numbers, both in the anterior and posterior stroma, compared to non-lens wearers [16].
[1] Wilhelmus KR, Coster DJ, Donovan HC, Falcon MG, Jones BR. Prognostic indicators of herpetic keratitis: analysis of a five-year observation period after corneal ulceration. Arch Ophthalmol 1981;99:1578–82. [2] Liesegang TJ. Physiologic changes of the cornea with contact lens wear. CLAO J 2002;28(January (1)):12–27. [3] Easty DL. Manifestations of immunodeficiency diseases in ophthalmology. Trans Ophthalmol Soc UK 1977;97:8–17. [4] Easty D, Entwistle C, Funk A, Witcher J. Herpes simplex keratitis and keratoconus in the atopic patient. A clinical and immunological study. Trans Ophthalmol Soc UK 1975;95:267–76. [5] Efron N. Contact lens-induced changes in the anterior eye as observed in vivo with the confocal microscope. Prog Retin Eye Res 2007;26:398–436. [6] Tran MT, Ritchie MH, Lausch RN, Oakes JE. Calcitonin gene-related peptide induces IL-8 synthesis in human corneal epithelial cells. J Immunol 2000;164:4307–12. [7] Tran MT, Lausch RN, Oakes JE. Substance P differentially stimulates IL-8 synthesis in human cornea epithelial cells. Invest Ophthalmol Vis Sci 2000;41:3871–7. [8] Thomas J, Gangappa S, Kanangat S, Rouse BT. On the essential involvement of neutrophils in the immunopathologic disease: herpetic stromal keratitis. J Immunol 1997;158:1383–91. [9] Bansal AK, Mustonen RK, McDonald MB. High resolution in vivo scanning confocal microscopy of the cornea in long term contact lens wear. Invest Ophthalmol Vis Sci 1997;38:S138. [10] Patel SV, McLaren JW, Hodge DO, Bourne WM. Confocal microscopy in vivo in corneas of long-term contact lens wearers. Invest Ophthalmol Vis Sci 2002;43:995–1003. [11] Niederkorn JY, Peeler JS, Mellon J. Phagocytosis of particulate antigens by corneal epithelial cells stimulates interleukin-1 secretion and migration of Langerhans cells into the central cornea. Reg Immunol 1989;2:83–90. [12] Ren DH, Petroll WM, Jester JV, Ho-Fan J, Cavanagh HD. The relationship between contact lens oxygen permeability and binding of Pseudomonas aeruginosa to human corneal epithelial cells after overnight and extended wear. CLAO J 1999;25:80–100 [Erratum 25, 175]. [13] Tsubota K, Yamada M. Corneal epithelial alterations induced by disposable contact-lens wear. Ophthalmology 1992;99:1193–6. [14] Cubitt CL, Lausch RN, Oakes JE. Differences in interleukin-6 gene expression between cultured human corneal epithelial cells and keratocytes. Invest Ophthalmol Vis Sci 1995;36:330–6. [15] Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, et al. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 1985;76:1427–35. [16] Weed KH, Macewen CJ, Cox A, McGhee CN. Quantitative analysis of corneal microstructure in keratoconus utilising in vivo confocal microscopy. Eye 2006, http://dx.doi.org/10.1038/sj.eye.6702286. [17] Gillette TE, Chandler JW, Greiner JV. Langerhans cells of the ocular surface. Ophthalmology 1982;89:700–11. [18] Jager MJ, Bradley D, Atherton S, Streilein JW. Presence of Langerhans cells in the central cornea linked to the development of ocular herpes in mice. Exp Eye Res 1992;54:835–41. [19] Zhivov A, Stave J, Vollmar B, Guthoff R. In vivo confocal microscopic evaluation of Langerhans cell density and distribution in the corneal epithelium of healthy volunteers and contact lens wearers. Cornea 2007;26(1):47–54.