Ocular Surface Herpetic Disease
Özet
This chapter provides a comprehensive overview of ocular surface diseases caused by herpes viruses, with a particular focus on herpes simplex virus (HSV) keratitis. Herpes viruses are DNA viruses capable of establishing latent infections and reactivating later in life. Among them, HSV-1 is the most common cause of ocular involvement and remains a leading infectious cause of corneal blindness worldwide. HSV infections may present as primary or recurrent disease and can affect multiple ocular structures including the eyelids, conjunctiva, cornea, uvea, and retina. The chapter describes the classification of HSV keratitis into epithelial, stromal, and endothelial forms, detailing their clinical manifestations, pathogenesis, differential diagnosis, and laboratory diagnostic methods. Evidence-based management strategies are discussed, including topical and systemic antiviral therapy, corticosteroid use, long-term antiviral prophylaxis, and treatment approaches supported by the Herpetic Eye Disease Study (HEDS). Potential complications such as corneal scarring, neovascularization, neurotrophic keratopathy, and permanent vision loss are also addressed. Emphasis is placed on the importance of early diagnosis, appropriate treatment, and prevention of recurrence. The chapter further outlines risk factors, immunological influences, and surgical management options, providing clinicians with practical guidance for the diagnosis and management of herpetic ocular disease.
Bu bölüm, herpes virüslerinin oküler yüzeyde oluşturduğu hastalıkları ve özellikle herpes simpleks virüsüne (HSV) bağlı gelişen keratit tablolarını kapsamlı biçimde ele almaktadır. Herpes virüsleri, latent enfeksiyon oluşturabilen ve tekrar aktive olabilen DNA virüsleridir. Göz tutulumunda en sık etken HSV-1 olup, dünya genelinde önemli bir görme kaybı nedeni olarak kabul edilmektedir. HSV enfeksiyonları primer veya rekürren olarak ortaya çıkabilir ve göz kapağı, konjonktiva, kornea, uvea ve retina gibi birçok oküler yapıyı etkileyebilir. Bölümde HSV keratitinin epitelyal, stromal ve endotelyal formları; klinik bulguları, patogenezi, ayırıcı tanısı ve laboratuvar tanı yöntemleri ayrıntılı olarak açıklanmaktadır. Ayrıca antiviral tedaviler, kortikosteroid kullanımı, uzun dönem profilaksi ve Herpetic Eye Disease Study (HEDS) sonuçlarına dayanan tedavi yaklaşımları ele alınmaktadır. Herpetik göz hastalığının komplikasyonları arasında korneal skar, neovaskülarizasyon, nörotrofik keratopati ve kalıcı görme kaybı yer almaktadır. Bu nedenle erken tanı, uygun tedavi ve rekürrenslerin önlenmesi büyük önem taşır. Bölüm ayrıca hastalığın risk faktörleri, immünolojik etkiler ve cerrahi tedavi seçenekleri hakkında da klinisyenlere yol gösterici bilgiler sunmaktadır.
Referanslar
Roizman B, Knipe DM, Whitley RJ. Herpes simplex viruses. In: Fields Virology. Clin Microbiol Rev. 2007;20(1):80–109. doi:10.1128/CMR.00031-06
Pavan-Langston D. Ocular viral infections. Med Clin North Am. 1983;67(5):973–990. doi:10.1016/S0025-7125(16)31464-6
Nicoll MP, Proença JT, Efstathiou S. The molecular basis of herpes simplex virus latency. FEMS Microbiol Rev. 2012;36(3):684–705. doi:10.1111/j.1574-6976.2011.00320.x
Looker KJ, Magaret AS, May MT, Turner KME, Vickerman P, Newman LM, et al. Global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 2012. PLoS One. 2015;10(10):e0140765. doi:10.1371/journal.pone.0140765
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448–462. doi:10.1016/j.survophthal.2012.01.005
Toma HS, Murina AT, Areaux RG Jr, Neumann DM, Bhattacharjee PS, Foster TP, et al. Ocular herpes simplex virus type 1 infection: clinical manifestations and management. Clin Ophthalmol. 2008;2(2):417–425. doi:10.2147/OPTH.S2702
Lairson DR, Begley CE, Reynolds TF, Wilhelmus KR. Prevention of herpes simplex virus eye disease: a cost-effectiveness analysis. Arch Ophthalmol. 2003;121(8):108–112. doi:10.1001/archopht.121.8.108
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185–191. doi:10.2147/OPTH.S80475
Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25(4):355–380. doi:10.1016/j.preteyeres.2006.05.001
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448–462. doi:10.1016/j.survophthal.2012.01.005
Rowe AM, St Leger AJ, Jeon S, Dhaliwal DK, Knickelbein JE, Hendricks RL. Herpes keratitis. Prog Retin Eye Res. 2013;32:88–101. doi:10.1016/j.preteyeres.2012.08.002
Wald A, Ashley-Morrow R. Serological testing for herpes simplex virus (HSV)-1 and HSV-2 infection. Clin Infect Dis. 2002;35(Suppl 2):S173–82. doi: 10.1086/342104.
Johnston C, Corey L. Current concepts for genital herpes simplex virus infection: diagnostics and pathogenesis of genital tract shedding. Clin Microbiol Rev. 2016;29(1):149–61. doi: 10.1128/CMR.00043-15.
Gilden DH, Tyler KL. Herpes simplex viruses. In: Human Herpesviruses. Springer; 2010. doi: 10.1007/978-1-4899-7448-8_36.
Kimberlin DW. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013;131(2):e635–46. doi: 10.1542/peds.2012-3216.
Whitley RJ, Roizman B. Herpes simplex viruses. Lancet. 2001;357(9267):1513–8. doi: 10.1016/S0140-6736(00)04638-9.
Mertz GJ. Asymptomatic shedding of herpes simplex virus 1 and 2: implications for prevention of transmission. J Infect Dis. 2008;198(8):1098–100. doi: 10.1086/591914.
Awasthi S, Hook LM, Pardi N, Wang F, Myles A, Cancro MP, et al. Maternal immunization confers protection against neonatal herpes simplex mortality and behavioral morbidity. Sci Transl Med. 2019;11(487):eaau6039. doi: 10.1126/scitranslmed.aau6039.
Melvin AJ, Mohan KM, Vora SB, Selke S, Sullivan E, Wald A. Neonatal herpes simplex virus infection: epidemiology and outcomes in the modern era. J Pediatric Infect Dis Soc. 2022;11(3):94–101. doi: 10.1093/jpids/piab105.
Held K, Derfuss T. Control of HSV-1 latency in human trigeminal ganglia—current overview. J Neurovirol. 2011;17(6):518–27. doi: 10.1007/s13365-011-0063-0.
Harrison KS, Jones C. Regulation of herpes simplex virus type 1 latency-reactivation cycle and ocular disease by cellular signaling pathways. Exp Eye Res. 2022;218:109017. doi: 10.1016/j.exer.2022.109017.
Sauerbrei A. Optimal laboratory diagnosis of herpes simplex virus infections. Intervirology. 2016;59(5-6):287–93. doi:10.1159/000453396
Ashley RL. Performance and use of HSV type-specific serology test kits. Herpes. 2002;9(2):38–45. doi:10.1684/her.2002.9.38
Wald A, Ashley-Morrow R. Serological testing for herpes simplex virus (HSV)-1 and HSV-2 infection. Clin Infect Dis. 2002;35(Suppl 2):S173–82. doi:10.1086/342104
Kimberlin DW, Baley J; Committee on Infectious Diseases; Committee on Fetus and Newborn. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013;131(2):e635–46. doi:10.1542/peds.2012-3216
Simon JW, Longo F, Smith RS. Spontaneous resolution of herpes simplex blepharoconjunctivitis in children. Am J Ophthalmol. 1986;102(5):598-600. doi:10.1016/0002-9394(86)90530-1
Reddy JC, Rapuano CJ. Current concepts in the management of herpes simplex anterior segment eye disease. Curr Ophthalmol Rep. 2013;1:194-203. doi:10.1007/s40135-013-0024-2
Labib BA, Chigbu DI. Clinical management of herpes simplex virus keratitis. Diagnostics (Basel). 2022;12(10):2368. doi:10.3390/diagnostics12102368
Sibley D, Larkin DFP. Update on Herpes simplex keratitis management. Eye (Lond). 2020;34:2219-2226. doi:10.1038/s41433-020-01153-x
Wilhelmus KR. Herpes simplex virus keratitis: a treatment guideline. Ophthalmology. 2015;122(1):1-??. doi:10.1016/j.ophtha.2014.09.021
Rowe AM, St Leger AJ, Jeon S, Dhaliwal DK, Knickelbein JE, Hendricks RL. Herpes keratitis. Prog Retin Eye Res. 2013;32:88-101. doi:10.1016/j.preteyeres.2012.08.002
Young RC, Hodge DO, Liesegang TJ, Baratz KH. Incidence, recurrence, and outcomes of herpes simplex virus eye disease in Olmsted County, Minnesota, 1976-2007: the effect of oral antiviral prophylaxis. Arch Ophthalmol. 2010;128(9):1178-1183. doi:10.1001/archophthalmol.2010.187
Liesegang TJ. Epidemiology of ocular herpes simplex. Natural history in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989;107(8):1160-1165. doi:10.1001/archopht.1989.01070020226030
Sibley D, Larkin DFP. Update on Herpes simplex keratitis management. Eye (Lond). 2020;34:2219-2226. doi:10.1038/s41433-020-01153-x
Liesegang TJ. Classification of herpes simplex virus keratitis. Cornea. 1999;18(2):144-154. doi:10.1097/00003226-199903000-00002
Sibley D, Larkin DFP. Update on Herpes simplex keratitis management. Eye (Lond). 2020;34:2219-2226. doi:10.1038/s41433-020-01153-x
White ML, Chodosh J. Herpes Simplex Virus Keratitis: A Treatment Guideline [Internet]. American Academy of Ophthalmology; 2014 [cited 2026 Feb 14]. Available from: https://www.aao.org/education/clinical-statement/herpes-simplex-virus-keratitis-treatment-guideline
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185–191. doi:10.2147/OPTH.S80475
Wilhelmus KR; Herpetic Eye Disease Study Group. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Ophthalmology. 2015;122(1):1–9. doi:10.1016/j.ophtha.2014.09.021
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219–2226. doi:10.1038/s41433-020-01153-x
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185–191. doi:10.2147/OPTH.S80475
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219–2226. doi:10.1038/s41433-020-01153-x
Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25(4):355–380. doi:10.1016/j.preteyeres.2006.05.001
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Ophthalmology. 2015;122(1):1–9. doi:10.1016/j.ophtha.2014.09.021
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448–462. doi:10.1016/j.survophthal.2012.01.005
Rowe AM, St Leger AJ, Jeon S, Dhaliwal DK, Knickelbein JE, Hendricks RL. Herpes keratitis. Prog Retin Eye Res. 2013;32:88–101. doi:10.1016/j.preteyeres.2012.08.002
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219–2226. doi:10.1038/s41433-020-01153-x
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Ophthalmology. 2015;122(1):1–9. doi:10.1016/j.ophtha.2014.09.021
Müller LJ, Pels E, Vrensen GFJM. The specific architecture of the human corneal nerves and its clinical implications. Prog Retin Eye Res. 2003;22(5):605–633. doi:10.1016/S1350-9462(03)00026-2
Hamrah P, Cruzat A, Dastjerdi MH, Zheng L, Shahatit BM, Bayhan HA, et al. Corneal sensation and subbasal nerve alterations in herpes simplex keratitis: an in vivo confocal microscopy study. Ophthalmology. 2010;117(10):1930–1936.doi:10.1016/j.ophtha.2010.02.020
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219–2226. doi:10.1038/s41433-020-01153-x
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185–191. doi:10.2147/OPTH.S80475
Poon SHL, Wong WHL, Lo ACY, Yuan H, Chen CF, Jhanji V, et al. A systematic review on advances in diagnostics for herpes simplex keratitis. Surv Ophthalmol. 2021;66(3):514–530. doi:10.1016/j.survophthal.2020.09.008
Liu L, Azher TN. Herpes Simplex Virus (HSV) Keratitis. In: Sharma N, ed. Keratitis. Singapore: Springer; 2020. doi:10.1007/978-981-15-8811-2_13
Matoba AY, Peterson JR, Wilhelmus KR. Dendritiform keratopathy associated with exposure to polyquaternium-1, a common ophthalmic preservative. Ophthalmology. 2016;123(3):451-456. doi:10.1016/j.ophtha.2015.10.063
Vera-Duarte GR, Jimenez-Collado D, Kahuam-López N, Ramirez-Miranda A, Graue-Hernandez EO, Navas A, Rosenblatt MI. Neurotrophic keratopathy: General features and new therapies. Surv Ophthalmol. 2024;69(5):789-804. doi:10.1016/j.survophthal.2024.04.004
Morphology of epithelial keratitis in herpes zoster ophthalmicus. Acta Ophthalmol Scand. 2000. doi:10.1034/j.1600-0420.2000.078006651.x
Herpetic Eye Disease Study Group. A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial. Arch Ophthalmol. 1997;115(6):703-712. doi:10.1001/archopht.1997.01100150705001
Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007;5(3):240-250. doi:10.1016/S1542-0124(12)70614-6
Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007;5(3):240-250. doi:10.1016/S1542-0124(12)70614-6
Hoh HB, Hurley C, Claoue C, Viswalingham M, Easty DL, Goldschmidt P, Collum LM. Randomised trial of ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis: a multicentre study. Br J Ophthalmol. 1996;80(2):140-143. doi:10.1136/bjo.80.2.140
Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007;5(3):240-250. doi:10.1016/S1542-0124(12)70614-6
Sozen E, et al. Comparison of efficacy of oral valacyclovir and topical acyclovir in the treatment of herpes simplex keratitis: a randomized clinical trial. Chemotherapy. 2006;52(1):29-31. doi:10.1159/000090239
Wilhelmus KR, Coster DJ, Jones BR. Acyclovir and debridement in the treatment of ulcerative herpetic keratitis. Am J Ophthalmol. 1981;91(3):323-327. doi:10.1016/0002-9394(81)90284-1
Al-Nouri ZL, Reese JA, Terrell DR, Vesely SK, George JN. Drug-induced thrombotic microangiopathy: a systematic review of published reports. Blood. 2015;125(4):616-618. doi:10.1182/blood-2014-11-611335
Smith JP, Weller S, Johnson B, Nicotera J, Luther JM, Haas DW. Pharmacokinetics of acyclovir and its metabolites in cerebrospinal fluid and systemic circulation after administration of high-dose valacyclovir in subjects with normal and impaired renal function. Antimicrob Agents Chemother. 2010;54(3):1146-1151. doi:10.1128/AAC.00729-09.
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448-462. doi:10.1016/j.survophthal.2012.01.005
Liesegang TJ. Epidemiology of ocular herpes simplex. Natural history in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989;107(8):1160-1165. doi:10.1001/archopht.1989.01070020226030
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Rowe AM, St Leger AJ, Jeon S, Dhaliwal DK, Knickelbein JE, Hendricks RL. Herpes keratitis. Prog Retin Eye Res. 2013;32:88-101. doi:10.1016/j.preteyeres.2012.08.002
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448-462. doi:10.1016/j.survophthal.2012.01.005
Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25(4):355-380. doi:10.1016/j.preteyeres.2006.05.001
Liesegang TJ. Epidemiology of ocular herpes simplex. Arch Ophthalmol. 1989;107(8):1160-1165. doi:10.1001/archopht.1989.01070020226030
Wilhelmus KR. Diagnosis and management of herpes simplex stromal keratitis. Cornea. 2007;26(9 Suppl 1):S12-S19. doi:10.1097/ICO.0b013e318157a6c1
Jabs DA. Immunosuppression for the uveitides. Ophthalmology. 2018;125(2):193-202. doi:10.1016/j.ophtha.2017.08.023
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Liesegang TJ. Varicella-zoster virus infection. Curr Opin Ophthalmol. 2004;15(6):531-536. doi:10.1097/01.icu.0000136663.88946.37
Toma HS, Murina AT, Areaux RG Jr, Neumann DM, Bhattacharjee PS, Foster TP, et al. Ocular herpes simplex virus type 1 infection: clinical manifestations and management. Clin Ophthalmol. 2008;2(2):417-425. doi:10.2147/OPTH.S2702
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185-191. doi:10.2147/OPTH.S80475
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Wilhelmus KR; Herpetic Eye Disease Study Group. The Herpetic Eye Disease Study: background and design. Arch Ophthalmol. 1994;112(3):315-322. doi:10.1001/archopht.1994.01090150051024
Herpetic Eye Disease Study Group. A randomized controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Arch Ophthalmol. 1994;112(3):322-329. doi:10.1001/archopht.1994.01090150058025
Herpetic Eye Disease Study Group. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med. 1998;339(5):300-306. doi:10.1056/NEJM199807303390503
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus stromal keratitis. Ophthalmology. 2015;122(1):1-9. doi:10.1016/j.ophtha.2014.09.021
Herpetic Eye Disease Study Group. Topical corticosteroids in herpes simplex stromal keratitis. Arch Ophthalmol. 1994;112(3):322-329. doi:10.1001/archopht.1994.01090150058025
Jeng BH, Gritz DC, Kumar AB, Holsclaw DS, Porco TC, Smith SD, et al. Epidemiology of ulcerative keratitis in Northern California. Arch Ophthalmol. 2010;128(8):1022-1028. doi:10.1001/archophthalmol.2010.152
Herpetic Eye Disease Study Group. Oral acyclovir for herpes simplex virus stromal keratitis. Arch Ophthalmol. 1996;114(9):1065-1072. doi:10.1001/archopht.1996.01100140275001
Colin J, Hoh HB, Easty DL, Herbort CP. Ganciclovir ophthalmic gel in the treatment of herpes simplex keratitis. Acta Ophthalmol Scand Suppl. 1997;224:19-23. doi:10.1111/j.1600-0420.1997.tb00442.x
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448-462. doi:10.1016/j.survophthal.2012.01.005
Herpetic Eye Disease Study Group. Oral acyclovir for herpes simplex virus stromal keratitis. Arch Ophthalmol. 1996;114(9):1065-1072. doi:10.1001/archopht.1996.01100140275001
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Toma HS, Murina AT, Areaux RG Jr, Neumann DM, Bhattacharjee PS, Foster TP, et al. Ocular herpes simplex virus type 1 infection: clinical manifestations and management. Clin Ophthalmol. 2008;2(2):417-425. doi:10.2147/OPTH.S2702
Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25(4):355-380. doi:10.1016/j.preteyeres.2006.05.001
Wilhelmus KR. Diagnosis and management of herpes simplex stromal keratitis. Cornea. 2007;26(9 Suppl 1):S12-S19. doi:10.1097/ICO.0b013e318157a6c1
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Miserocchi E, Fogliato G, Bianchi I, Bandello F, Modorati G. Clinical features of ocular herpetic infection in an Italian referral center. Cornea. 2014;33(6):565-570. doi:10.1097/ICO.0000000000000122
Tugal-Tutkun I, Otük-Yasar B, Altinkurt E. Clinical features and prognosis of herpetic anterior uveitis: a retrospective study of 111 cases. Ophthalmology. 2009;116(9):1603-1609. doi:10.1016/j.ophtha.2009.02.034
Sungur G, Hazirolan D, Duran S, Satana B, Arikan G, Duman S. Clinical features and prognosis of herpetic anterior uveitis. Ocul Immunol Inflamm. 2009;17(6):402-406. doi:10.3109/09273940903311634
Wand M, Gilbert CM, Liesegang TJ. Latanoprost and herpes simplex keratitis. Am J Ophthalmol. 1999;127(5):602-604. doi:10.1016/S0002-9394(98)00429-2
Cunningham ET Jr, Short GA, Irvine AR, Duker JS, Margolis TP. Aciclovir therapy for herpes simplex virus–associated anterior uveitis. Ophthalmology. 1996;103(3):437-442. doi:10.1016/S0161-6420(96)30666-0
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Ophthalmology. 2015;122(1):1-9. doi:10.1016/j.ophtha.2014.09.021
Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007;5(3):240-250. doi:10.1016/S1542-0124(12)70614-6
Dua HS, Saini JS, Azuara-Blanco A, Gupta P. Limbal stem cell deficiency: concept, aetiology, clinical presentation, diagnosis and management. Indian J Ophthalmol. 2000;48(2):83-92. doi:10.4103/0301-4738.27049
Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571-579. doi:10.2147/OPTH.S45921
Hamrah P, Cruzat A, Dastjerdi MH, Zheng L, Shahatit BM, Bayhan HA, et al. Corneal sensation and subbasal nerve alterations in herpes simplex keratitis: an in vivo confocal microscopy study. Ophthalmology. 2010;117(10):1930-1936. doi:10.1016/j.ophtha.2010.02.020
Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003;17(8):989-995. doi:10.1038/sj.eye.6700616
Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571-579. doi:10.2147/OPTH.S45921
Dua HS, Said DG, Messmer EM, Rolando M, Benitez-Del-Castillo JM, Hossain PN, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107-131. doi:10.1016/j.preteyeres.2018.04.003
Dua HS, Said DG, Messmer EM, Rolando M, Benitez-Del-Castillo JM, Hossain PN, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107-131. doi:10.1016/j.preteyeres.2018.04.003
Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007;5(3):240-250. doi:10.1016/S1542-0124(12)70614-6
Dua HS, Said DG, Messmer EM, Rolando M, Benitez-Del-Castillo JM, Hossain PN, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107-131. doi:10.1016/j.preteyeres.2018.04.003
Wilhelmus KR. Diagnosis and management of herpes simplex stromal keratitis. Cornea. 2007;26(9 Suppl 1):S12-S19. doi:10.1097/ICO.0b013e318157a6c1
Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea. 2001;20(1):1-13. doi:10.1097/00003226-200101000-00001
Deng SX, Lee WB, Hammersmith KM, Kuo AN, Li JY, Shen JF, et al. Descemet membrane endothelial keratoplasty: safety and outcomes. Ophthalmology. 2018;125(2):295-310. doi:10.1016/j.ophtha.2017.08.037
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448-462. doi:10.1016/j.survophthal.2012.01.005
Schornack MM. Scleral lenses: a literature review. Eye Contact Lens. 2015;41(1):3-11. doi:10.1097/ICL.0000000000000092
Cogan DG, Kuwabara T. Lipid keratopathy and its pathogenesis. Arch Ophthalmol. 1958;59(2):219-227. doi:10.1001/archopht.1958.00940040221009
Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol. 2001;12(4):242-249. doi:10.1097/00055735-200108000-00005
Liu J, Sheha H, Fu Y, Liang L, Tseng SCG. Update on amniotic membrane transplantation. Expert Rev Ophthalmol. 2010;5(5):645-661. doi:10.1586/eop.10.63
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus stromal keratitis. Ophthalmology. 2015;122(1):1-9. doi:10.1016/j.ophtha.2014.09.021
Anwar M, Teichmann KD. Deep lamellar keratoplasty: surgical techniques for anterior lamellar keratoplasty with and without baring of Descemet’s membrane. Cornea. 2002;21(4):374-383. doi:10.1097/00003226-200205000-00008
Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a global perspective. Bull World Health Organ. 2001;79(3):214-221. doi:10.2471/BLT.01.96320
Coster DJ, Williams KA. The impact of corneal allograft rejection. Transplantation. 2005;80(3):243-248. doi:10.1097/01.TP.0000164108.08419.2C
Toma HS, Murina AT, Areaux RG Jr, Neumann DM, Bhattacharjee PS, Foster TP, et al. Ocular herpes simplex virus type 1 infection: clinical manifestations and management. Clin Ophthalmol. 2008;2(2):417-425. doi:10.2147/OPTH.S2702
Sharma A, Kaur R, Kumar S, Gupta P, Pandav SS, Patnaik B. Fibrin glue versus N-butyl-2-cyanoacrylate in corneal perforations. Ophthalmology. 2003;110(2):291-298. doi:10.1016/S0161-6420(02)01572-7
Dua HS, Gomes JAP, King AJ, Maharajan VS. The amniotic membrane in ophthalmology. Surv Ophthalmol. 2004;49(1):51-77. doi:10.1016/j.survophthal.2003.10.004
Aldave AJ, Sangwan VS, Basu S, Basak SK, Hovakimyan E, Gevorgyan O, et al. International outcomes of the Boston type I keratoprosthesis. Ophthalmology. 2012;119(8):1530-1538.doi:10.1016/j.ophtha.2012.01.041
Roberts MB, Fishman JA. Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the “Net State of Immunosuppression”. Clin Infect Dis. 2021;73(7):e1302-e1317. doi:10.1093/cid/ciaa1189
Hoepelman AIM, Meiland R, Lichtenauer-Kaligis EGR, van Buuren M, Kastelein JJP. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol. 1999;26(3-4):259-265. doi:10.1111/j.1574-695X.1999.tb01397.x
Fugier-Vivier I, Servet-Delprat C, Rivailler P, Rissoan MC, Liu YJ, Rabourdin-Combe C. Measles Virus Suppresses Cell-mediated Immunity by Interfering with the Survival and Functions of Dendritic and T Cells. J Exp Med. 1997;186(6):813-823. doi:10.1084/jem.186.6.813
Schwartz GS, Holland EJ. Oral acyclovir for the management of herpes simplex virus keratitis in children. Am J Ophthalmol. 2000;129(2):175-180. doi:10.1016/S0002-9394(99)00312-9
Young RC, Hodge DO, Liesegang TJ, Baratz KH. Epidemiology and recurrence of herpes simplex virus eye disease: a population-based study. Arch Ophthalmol. 2010;128(9):1178-1183. doi:10.1001/archophthalmol.2010.187
O’Brien TP, Maguire MG, Fink NE, Alfonso E, McDonnell P. Epithelial healing in herpes simplex virus keratitis: factors associated with delayed healing. Ophthalmology. 1995;102(10):1547-1554. doi:10.1016/S0161-6420(95)30848-2
Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea. 2001;20(1):1-13. doi:10.1097/00003226-200101000-00001
Schwartz GS, Holland EJ. Oral acyclovir for the management of herpes simplex virus keratitis in children. Am J Ophthalmol. 2000;129(2):175-180. doi:10.1016/S0002-9394(99)00312-9
Akova YA, Onat M, Sener EC, Eroğlu A. Bilateral herpetic keratitis: clinical characteristics and risk factors. Cornea. 2001;20(1):28-32. doi:10.1097/00003226-200101000-00006
Akova YA, Onat M, Sener EC, Eroğlu A. Bilateral herpetic keratitis: clinical characteristics and risk factors. Cornea. 2001;20(1):28-32. doi:10.1097/00003226-200101000-00006
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185-191. doi:10.2147/OPTH.S80475
Akova YA, Onat M, Sener EC, Eroğlu A. Bilateral herpetic keratitis: clinical characteristics and risk factors. Cornea. 2001;20(1):28-32. doi:10.1097/00003226-200101000-00006
Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387(10023):1109-1122. doi:10.1016/S0140-6736(15)00149-X
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185-191. doi:10.2147/OPTH.S80475
Akova YA, Onat M, Sener EC, Eroğlu A. Bilateral herpetic keratitis: clinical characteristics and risk factors. Cornea. 2001;20(1):28-32. doi:10.1097/00003226-200101000-00006
Johnston C, Corey L. Current concepts for genital herpes simplex virus infection: diagnostics and pathogenesis of genital tract shedding. Clin Microbiol Rev. 2016;29(1):149-161. doi:10.1128/CMR.00043-15
Herpetic Eye Disease Study Group. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med. 1998;339(5):300-306. doi:10.1056/NEJM199807303390503
Herpetic Eye Disease Study Group. Risk factors for recurrence of herpes simplex virus eye disease. Arch Ophthalmol. 2000;118(8):1030-1036. doi:10.1001/archopht.118.8.1030
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus stromal keratitis. Ophthalmology. 2015;122(1):1-9. doi:10.1016/j.ophtha.2014.09.021
Woodward DF, Krauss AH, Chen J, Lai RK, Spada CS, Burk RM, et al. The pharmacology of prostaglandin F2α analogs in the eye. Surv Ophthalmol. 2007;52(Suppl 2):S1-S2. doi:10.1016/j.survophthal.2007.08.002
Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986-1000. doi:10.1161/ATVBAHA.110.207449
Wand M, Gilbert CM, Liesegang TJ. Latanoprost and herpes simplex keratitis. Am J Ophthalmol. 1999;127(5):602-604. doi:10.1016/S0002-9394(98)00429-2
Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017;17(4):233-247. doi:10.1038/nri.2017.1
O’Brien TP, Maguire MG, Fink NE, Alfonso E, McDonnell P. Epithelial healing in herpes simplex virus keratitis: factors associated with delayed healing. Ophthalmology. 1995;102(10):1547-1554. doi:10.1016/S0161-6420(95)30848-2
Kaye SB, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25(4):355-380. doi:10.1016/j.preteyeres.2006.05.001
Dhaliwal DK, Romanowski EG, Yates KA, Gordon YJ. Experimental reactivation of ocular herpes simplex virus type 1 by laser in a rabbit model. Ophthalmology. 1999;106(10):1926-1930. doi:10.1016/S0161-6420(99)90405-3
Nagy ZZ, McDonnell PJ. Herpes simplex keratitis after excimer laser refractive surgery. Ophthalmology. 1999;106(8):1400-1404. doi:10.1016/S0161-6420(99)90352-7
Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea. 2001;20(1):1-13. doi:10.1097/00003226-200101000-00001
Wilhelmus KR. Diagnosis and management of herpes simplex stromal keratitis. Cornea. 2007;26(9 Suppl 1):S12-S19. doi:10.1097/ICO.0b013e318157a6c1
Herpetic Eye Disease Study Group. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med. 1998;339(5):300-306. doi:10.1056/NEJM199807303390503
Referanslar
Roizman B, Knipe DM, Whitley RJ. Herpes simplex viruses. In: Fields Virology. Clin Microbiol Rev. 2007;20(1):80–109. doi:10.1128/CMR.00031-06
Pavan-Langston D. Ocular viral infections. Med Clin North Am. 1983;67(5):973–990. doi:10.1016/S0025-7125(16)31464-6
Nicoll MP, Proença JT, Efstathiou S. The molecular basis of herpes simplex virus latency. FEMS Microbiol Rev. 2012;36(3):684–705. doi:10.1111/j.1574-6976.2011.00320.x
Looker KJ, Magaret AS, May MT, Turner KME, Vickerman P, Newman LM, et al. Global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 2012. PLoS One. 2015;10(10):e0140765. doi:10.1371/journal.pone.0140765
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448–462. doi:10.1016/j.survophthal.2012.01.005
Toma HS, Murina AT, Areaux RG Jr, Neumann DM, Bhattacharjee PS, Foster TP, et al. Ocular herpes simplex virus type 1 infection: clinical manifestations and management. Clin Ophthalmol. 2008;2(2):417–425. doi:10.2147/OPTH.S2702
Lairson DR, Begley CE, Reynolds TF, Wilhelmus KR. Prevention of herpes simplex virus eye disease: a cost-effectiveness analysis. Arch Ophthalmol. 2003;121(8):108–112. doi:10.1001/archopht.121.8.108
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185–191. doi:10.2147/OPTH.S80475
Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25(4):355–380. doi:10.1016/j.preteyeres.2006.05.001
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448–462. doi:10.1016/j.survophthal.2012.01.005
Rowe AM, St Leger AJ, Jeon S, Dhaliwal DK, Knickelbein JE, Hendricks RL. Herpes keratitis. Prog Retin Eye Res. 2013;32:88–101. doi:10.1016/j.preteyeres.2012.08.002
Wald A, Ashley-Morrow R. Serological testing for herpes simplex virus (HSV)-1 and HSV-2 infection. Clin Infect Dis. 2002;35(Suppl 2):S173–82. doi: 10.1086/342104.
Johnston C, Corey L. Current concepts for genital herpes simplex virus infection: diagnostics and pathogenesis of genital tract shedding. Clin Microbiol Rev. 2016;29(1):149–61. doi: 10.1128/CMR.00043-15.
Gilden DH, Tyler KL. Herpes simplex viruses. In: Human Herpesviruses. Springer; 2010. doi: 10.1007/978-1-4899-7448-8_36.
Kimberlin DW. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013;131(2):e635–46. doi: 10.1542/peds.2012-3216.
Whitley RJ, Roizman B. Herpes simplex viruses. Lancet. 2001;357(9267):1513–8. doi: 10.1016/S0140-6736(00)04638-9.
Mertz GJ. Asymptomatic shedding of herpes simplex virus 1 and 2: implications for prevention of transmission. J Infect Dis. 2008;198(8):1098–100. doi: 10.1086/591914.
Awasthi S, Hook LM, Pardi N, Wang F, Myles A, Cancro MP, et al. Maternal immunization confers protection against neonatal herpes simplex mortality and behavioral morbidity. Sci Transl Med. 2019;11(487):eaau6039. doi: 10.1126/scitranslmed.aau6039.
Melvin AJ, Mohan KM, Vora SB, Selke S, Sullivan E, Wald A. Neonatal herpes simplex virus infection: epidemiology and outcomes in the modern era. J Pediatric Infect Dis Soc. 2022;11(3):94–101. doi: 10.1093/jpids/piab105.
Held K, Derfuss T. Control of HSV-1 latency in human trigeminal ganglia—current overview. J Neurovirol. 2011;17(6):518–27. doi: 10.1007/s13365-011-0063-0.
Harrison KS, Jones C. Regulation of herpes simplex virus type 1 latency-reactivation cycle and ocular disease by cellular signaling pathways. Exp Eye Res. 2022;218:109017. doi: 10.1016/j.exer.2022.109017.
Sauerbrei A. Optimal laboratory diagnosis of herpes simplex virus infections. Intervirology. 2016;59(5-6):287–93. doi:10.1159/000453396
Ashley RL. Performance and use of HSV type-specific serology test kits. Herpes. 2002;9(2):38–45. doi:10.1684/her.2002.9.38
Wald A, Ashley-Morrow R. Serological testing for herpes simplex virus (HSV)-1 and HSV-2 infection. Clin Infect Dis. 2002;35(Suppl 2):S173–82. doi:10.1086/342104
Kimberlin DW, Baley J; Committee on Infectious Diseases; Committee on Fetus and Newborn. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013;131(2):e635–46. doi:10.1542/peds.2012-3216
Simon JW, Longo F, Smith RS. Spontaneous resolution of herpes simplex blepharoconjunctivitis in children. Am J Ophthalmol. 1986;102(5):598-600. doi:10.1016/0002-9394(86)90530-1
Reddy JC, Rapuano CJ. Current concepts in the management of herpes simplex anterior segment eye disease. Curr Ophthalmol Rep. 2013;1:194-203. doi:10.1007/s40135-013-0024-2
Labib BA, Chigbu DI. Clinical management of herpes simplex virus keratitis. Diagnostics (Basel). 2022;12(10):2368. doi:10.3390/diagnostics12102368
Sibley D, Larkin DFP. Update on Herpes simplex keratitis management. Eye (Lond). 2020;34:2219-2226. doi:10.1038/s41433-020-01153-x
Wilhelmus KR. Herpes simplex virus keratitis: a treatment guideline. Ophthalmology. 2015;122(1):1-??. doi:10.1016/j.ophtha.2014.09.021
Rowe AM, St Leger AJ, Jeon S, Dhaliwal DK, Knickelbein JE, Hendricks RL. Herpes keratitis. Prog Retin Eye Res. 2013;32:88-101. doi:10.1016/j.preteyeres.2012.08.002
Young RC, Hodge DO, Liesegang TJ, Baratz KH. Incidence, recurrence, and outcomes of herpes simplex virus eye disease in Olmsted County, Minnesota, 1976-2007: the effect of oral antiviral prophylaxis. Arch Ophthalmol. 2010;128(9):1178-1183. doi:10.1001/archophthalmol.2010.187
Liesegang TJ. Epidemiology of ocular herpes simplex. Natural history in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989;107(8):1160-1165. doi:10.1001/archopht.1989.01070020226030
Sibley D, Larkin DFP. Update on Herpes simplex keratitis management. Eye (Lond). 2020;34:2219-2226. doi:10.1038/s41433-020-01153-x
Liesegang TJ. Classification of herpes simplex virus keratitis. Cornea. 1999;18(2):144-154. doi:10.1097/00003226-199903000-00002
Sibley D, Larkin DFP. Update on Herpes simplex keratitis management. Eye (Lond). 2020;34:2219-2226. doi:10.1038/s41433-020-01153-x
White ML, Chodosh J. Herpes Simplex Virus Keratitis: A Treatment Guideline [Internet]. American Academy of Ophthalmology; 2014 [cited 2026 Feb 14]. Available from: https://www.aao.org/education/clinical-statement/herpes-simplex-virus-keratitis-treatment-guideline
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185–191. doi:10.2147/OPTH.S80475
Wilhelmus KR; Herpetic Eye Disease Study Group. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Ophthalmology. 2015;122(1):1–9. doi:10.1016/j.ophtha.2014.09.021
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219–2226. doi:10.1038/s41433-020-01153-x
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185–191. doi:10.2147/OPTH.S80475
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219–2226. doi:10.1038/s41433-020-01153-x
Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25(4):355–380. doi:10.1016/j.preteyeres.2006.05.001
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Ophthalmology. 2015;122(1):1–9. doi:10.1016/j.ophtha.2014.09.021
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448–462. doi:10.1016/j.survophthal.2012.01.005
Rowe AM, St Leger AJ, Jeon S, Dhaliwal DK, Knickelbein JE, Hendricks RL. Herpes keratitis. Prog Retin Eye Res. 2013;32:88–101. doi:10.1016/j.preteyeres.2012.08.002
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219–2226. doi:10.1038/s41433-020-01153-x
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Ophthalmology. 2015;122(1):1–9. doi:10.1016/j.ophtha.2014.09.021
Müller LJ, Pels E, Vrensen GFJM. The specific architecture of the human corneal nerves and its clinical implications. Prog Retin Eye Res. 2003;22(5):605–633. doi:10.1016/S1350-9462(03)00026-2
Hamrah P, Cruzat A, Dastjerdi MH, Zheng L, Shahatit BM, Bayhan HA, et al. Corneal sensation and subbasal nerve alterations in herpes simplex keratitis: an in vivo confocal microscopy study. Ophthalmology. 2010;117(10):1930–1936.doi:10.1016/j.ophtha.2010.02.020
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219–2226. doi:10.1038/s41433-020-01153-x
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185–191. doi:10.2147/OPTH.S80475
Poon SHL, Wong WHL, Lo ACY, Yuan H, Chen CF, Jhanji V, et al. A systematic review on advances in diagnostics for herpes simplex keratitis. Surv Ophthalmol. 2021;66(3):514–530. doi:10.1016/j.survophthal.2020.09.008
Liu L, Azher TN. Herpes Simplex Virus (HSV) Keratitis. In: Sharma N, ed. Keratitis. Singapore: Springer; 2020. doi:10.1007/978-981-15-8811-2_13
Matoba AY, Peterson JR, Wilhelmus KR. Dendritiform keratopathy associated with exposure to polyquaternium-1, a common ophthalmic preservative. Ophthalmology. 2016;123(3):451-456. doi:10.1016/j.ophtha.2015.10.063
Vera-Duarte GR, Jimenez-Collado D, Kahuam-López N, Ramirez-Miranda A, Graue-Hernandez EO, Navas A, Rosenblatt MI. Neurotrophic keratopathy: General features and new therapies. Surv Ophthalmol. 2024;69(5):789-804. doi:10.1016/j.survophthal.2024.04.004
Morphology of epithelial keratitis in herpes zoster ophthalmicus. Acta Ophthalmol Scand. 2000. doi:10.1034/j.1600-0420.2000.078006651.x
Herpetic Eye Disease Study Group. A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial. Arch Ophthalmol. 1997;115(6):703-712. doi:10.1001/archopht.1997.01100150705001
Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007;5(3):240-250. doi:10.1016/S1542-0124(12)70614-6
Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007;5(3):240-250. doi:10.1016/S1542-0124(12)70614-6
Hoh HB, Hurley C, Claoue C, Viswalingham M, Easty DL, Goldschmidt P, Collum LM. Randomised trial of ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis: a multicentre study. Br J Ophthalmol. 1996;80(2):140-143. doi:10.1136/bjo.80.2.140
Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007;5(3):240-250. doi:10.1016/S1542-0124(12)70614-6
Sozen E, et al. Comparison of efficacy of oral valacyclovir and topical acyclovir in the treatment of herpes simplex keratitis: a randomized clinical trial. Chemotherapy. 2006;52(1):29-31. doi:10.1159/000090239
Wilhelmus KR, Coster DJ, Jones BR. Acyclovir and debridement in the treatment of ulcerative herpetic keratitis. Am J Ophthalmol. 1981;91(3):323-327. doi:10.1016/0002-9394(81)90284-1
Al-Nouri ZL, Reese JA, Terrell DR, Vesely SK, George JN. Drug-induced thrombotic microangiopathy: a systematic review of published reports. Blood. 2015;125(4):616-618. doi:10.1182/blood-2014-11-611335
Smith JP, Weller S, Johnson B, Nicotera J, Luther JM, Haas DW. Pharmacokinetics of acyclovir and its metabolites in cerebrospinal fluid and systemic circulation after administration of high-dose valacyclovir in subjects with normal and impaired renal function. Antimicrob Agents Chemother. 2010;54(3):1146-1151. doi:10.1128/AAC.00729-09.
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448-462. doi:10.1016/j.survophthal.2012.01.005
Liesegang TJ. Epidemiology of ocular herpes simplex. Natural history in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989;107(8):1160-1165. doi:10.1001/archopht.1989.01070020226030
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Rowe AM, St Leger AJ, Jeon S, Dhaliwal DK, Knickelbein JE, Hendricks RL. Herpes keratitis. Prog Retin Eye Res. 2013;32:88-101. doi:10.1016/j.preteyeres.2012.08.002
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448-462. doi:10.1016/j.survophthal.2012.01.005
Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25(4):355-380. doi:10.1016/j.preteyeres.2006.05.001
Liesegang TJ. Epidemiology of ocular herpes simplex. Arch Ophthalmol. 1989;107(8):1160-1165. doi:10.1001/archopht.1989.01070020226030
Wilhelmus KR. Diagnosis and management of herpes simplex stromal keratitis. Cornea. 2007;26(9 Suppl 1):S12-S19. doi:10.1097/ICO.0b013e318157a6c1
Jabs DA. Immunosuppression for the uveitides. Ophthalmology. 2018;125(2):193-202. doi:10.1016/j.ophtha.2017.08.023
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Liesegang TJ. Varicella-zoster virus infection. Curr Opin Ophthalmol. 2004;15(6):531-536. doi:10.1097/01.icu.0000136663.88946.37
Toma HS, Murina AT, Areaux RG Jr, Neumann DM, Bhattacharjee PS, Foster TP, et al. Ocular herpes simplex virus type 1 infection: clinical manifestations and management. Clin Ophthalmol. 2008;2(2):417-425. doi:10.2147/OPTH.S2702
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185-191. doi:10.2147/OPTH.S80475
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Wilhelmus KR; Herpetic Eye Disease Study Group. The Herpetic Eye Disease Study: background and design. Arch Ophthalmol. 1994;112(3):315-322. doi:10.1001/archopht.1994.01090150051024
Herpetic Eye Disease Study Group. A randomized controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Arch Ophthalmol. 1994;112(3):322-329. doi:10.1001/archopht.1994.01090150058025
Herpetic Eye Disease Study Group. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med. 1998;339(5):300-306. doi:10.1056/NEJM199807303390503
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus stromal keratitis. Ophthalmology. 2015;122(1):1-9. doi:10.1016/j.ophtha.2014.09.021
Herpetic Eye Disease Study Group. Topical corticosteroids in herpes simplex stromal keratitis. Arch Ophthalmol. 1994;112(3):322-329. doi:10.1001/archopht.1994.01090150058025
Jeng BH, Gritz DC, Kumar AB, Holsclaw DS, Porco TC, Smith SD, et al. Epidemiology of ulcerative keratitis in Northern California. Arch Ophthalmol. 2010;128(8):1022-1028. doi:10.1001/archophthalmol.2010.152
Herpetic Eye Disease Study Group. Oral acyclovir for herpes simplex virus stromal keratitis. Arch Ophthalmol. 1996;114(9):1065-1072. doi:10.1001/archopht.1996.01100140275001
Colin J, Hoh HB, Easty DL, Herbort CP. Ganciclovir ophthalmic gel in the treatment of herpes simplex keratitis. Acta Ophthalmol Scand Suppl. 1997;224:19-23. doi:10.1111/j.1600-0420.1997.tb00442.x
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448-462. doi:10.1016/j.survophthal.2012.01.005
Herpetic Eye Disease Study Group. Oral acyclovir for herpes simplex virus stromal keratitis. Arch Ophthalmol. 1996;114(9):1065-1072. doi:10.1001/archopht.1996.01100140275001
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Toma HS, Murina AT, Areaux RG Jr, Neumann DM, Bhattacharjee PS, Foster TP, et al. Ocular herpes simplex virus type 1 infection: clinical manifestations and management. Clin Ophthalmol. 2008;2(2):417-425. doi:10.2147/OPTH.S2702
Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25(4):355-380. doi:10.1016/j.preteyeres.2006.05.001
Wilhelmus KR. Diagnosis and management of herpes simplex stromal keratitis. Cornea. 2007;26(9 Suppl 1):S12-S19. doi:10.1097/ICO.0b013e318157a6c1
Sibley D, Larkin DFP. Update on herpes simplex keratitis management. Eye (Lond). 2020;34(12):2219-2226. doi:10.1038/s41433-020-01153-x
Miserocchi E, Fogliato G, Bianchi I, Bandello F, Modorati G. Clinical features of ocular herpetic infection in an Italian referral center. Cornea. 2014;33(6):565-570. doi:10.1097/ICO.0000000000000122
Tugal-Tutkun I, Otük-Yasar B, Altinkurt E. Clinical features and prognosis of herpetic anterior uveitis: a retrospective study of 111 cases. Ophthalmology. 2009;116(9):1603-1609. doi:10.1016/j.ophtha.2009.02.034
Sungur G, Hazirolan D, Duran S, Satana B, Arikan G, Duman S. Clinical features and prognosis of herpetic anterior uveitis. Ocul Immunol Inflamm. 2009;17(6):402-406. doi:10.3109/09273940903311634
Wand M, Gilbert CM, Liesegang TJ. Latanoprost and herpes simplex keratitis. Am J Ophthalmol. 1999;127(5):602-604. doi:10.1016/S0002-9394(98)00429-2
Cunningham ET Jr, Short GA, Irvine AR, Duker JS, Margolis TP. Aciclovir therapy for herpes simplex virus–associated anterior uveitis. Ophthalmology. 1996;103(3):437-442. doi:10.1016/S0161-6420(96)30666-0
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Ophthalmology. 2015;122(1):1-9. doi:10.1016/j.ophtha.2014.09.021
Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007;5(3):240-250. doi:10.1016/S1542-0124(12)70614-6
Dua HS, Saini JS, Azuara-Blanco A, Gupta P. Limbal stem cell deficiency: concept, aetiology, clinical presentation, diagnosis and management. Indian J Ophthalmol. 2000;48(2):83-92. doi:10.4103/0301-4738.27049
Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571-579. doi:10.2147/OPTH.S45921
Hamrah P, Cruzat A, Dastjerdi MH, Zheng L, Shahatit BM, Bayhan HA, et al. Corneal sensation and subbasal nerve alterations in herpes simplex keratitis: an in vivo confocal microscopy study. Ophthalmology. 2010;117(10):1930-1936. doi:10.1016/j.ophtha.2010.02.020
Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003;17(8):989-995. doi:10.1038/sj.eye.6700616
Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571-579. doi:10.2147/OPTH.S45921
Dua HS, Said DG, Messmer EM, Rolando M, Benitez-Del-Castillo JM, Hossain PN, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107-131. doi:10.1016/j.preteyeres.2018.04.003
Dua HS, Said DG, Messmer EM, Rolando M, Benitez-Del-Castillo JM, Hossain PN, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107-131. doi:10.1016/j.preteyeres.2018.04.003
Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007;5(3):240-250. doi:10.1016/S1542-0124(12)70614-6
Dua HS, Said DG, Messmer EM, Rolando M, Benitez-Del-Castillo JM, Hossain PN, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107-131. doi:10.1016/j.preteyeres.2018.04.003
Wilhelmus KR. Diagnosis and management of herpes simplex stromal keratitis. Cornea. 2007;26(9 Suppl 1):S12-S19. doi:10.1097/ICO.0b013e318157a6c1
Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea. 2001;20(1):1-13. doi:10.1097/00003226-200101000-00001
Deng SX, Lee WB, Hammersmith KM, Kuo AN, Li JY, Shen JF, et al. Descemet membrane endothelial keratoplasty: safety and outcomes. Ophthalmology. 2018;125(2):295-310. doi:10.1016/j.ophtha.2017.08.037
Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448-462. doi:10.1016/j.survophthal.2012.01.005
Schornack MM. Scleral lenses: a literature review. Eye Contact Lens. 2015;41(1):3-11. doi:10.1097/ICL.0000000000000092
Cogan DG, Kuwabara T. Lipid keratopathy and its pathogenesis. Arch Ophthalmol. 1958;59(2):219-227. doi:10.1001/archopht.1958.00940040221009
Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol. 2001;12(4):242-249. doi:10.1097/00055735-200108000-00005
Liu J, Sheha H, Fu Y, Liang L, Tseng SCG. Update on amniotic membrane transplantation. Expert Rev Ophthalmol. 2010;5(5):645-661. doi:10.1586/eop.10.63
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus stromal keratitis. Ophthalmology. 2015;122(1):1-9. doi:10.1016/j.ophtha.2014.09.021
Anwar M, Teichmann KD. Deep lamellar keratoplasty: surgical techniques for anterior lamellar keratoplasty with and without baring of Descemet’s membrane. Cornea. 2002;21(4):374-383. doi:10.1097/00003226-200205000-00008
Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a global perspective. Bull World Health Organ. 2001;79(3):214-221. doi:10.2471/BLT.01.96320
Coster DJ, Williams KA. The impact of corneal allograft rejection. Transplantation. 2005;80(3):243-248. doi:10.1097/01.TP.0000164108.08419.2C
Toma HS, Murina AT, Areaux RG Jr, Neumann DM, Bhattacharjee PS, Foster TP, et al. Ocular herpes simplex virus type 1 infection: clinical manifestations and management. Clin Ophthalmol. 2008;2(2):417-425. doi:10.2147/OPTH.S2702
Sharma A, Kaur R, Kumar S, Gupta P, Pandav SS, Patnaik B. Fibrin glue versus N-butyl-2-cyanoacrylate in corneal perforations. Ophthalmology. 2003;110(2):291-298. doi:10.1016/S0161-6420(02)01572-7
Dua HS, Gomes JAP, King AJ, Maharajan VS. The amniotic membrane in ophthalmology. Surv Ophthalmol. 2004;49(1):51-77. doi:10.1016/j.survophthal.2003.10.004
Aldave AJ, Sangwan VS, Basu S, Basak SK, Hovakimyan E, Gevorgyan O, et al. International outcomes of the Boston type I keratoprosthesis. Ophthalmology. 2012;119(8):1530-1538.doi:10.1016/j.ophtha.2012.01.041
Roberts MB, Fishman JA. Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the “Net State of Immunosuppression”. Clin Infect Dis. 2021;73(7):e1302-e1317. doi:10.1093/cid/ciaa1189
Hoepelman AIM, Meiland R, Lichtenauer-Kaligis EGR, van Buuren M, Kastelein JJP. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol. 1999;26(3-4):259-265. doi:10.1111/j.1574-695X.1999.tb01397.x
Fugier-Vivier I, Servet-Delprat C, Rivailler P, Rissoan MC, Liu YJ, Rabourdin-Combe C. Measles Virus Suppresses Cell-mediated Immunity by Interfering with the Survival and Functions of Dendritic and T Cells. J Exp Med. 1997;186(6):813-823. doi:10.1084/jem.186.6.813
Schwartz GS, Holland EJ. Oral acyclovir for the management of herpes simplex virus keratitis in children. Am J Ophthalmol. 2000;129(2):175-180. doi:10.1016/S0002-9394(99)00312-9
Young RC, Hodge DO, Liesegang TJ, Baratz KH. Epidemiology and recurrence of herpes simplex virus eye disease: a population-based study. Arch Ophthalmol. 2010;128(9):1178-1183. doi:10.1001/archophthalmol.2010.187
O’Brien TP, Maguire MG, Fink NE, Alfonso E, McDonnell P. Epithelial healing in herpes simplex virus keratitis: factors associated with delayed healing. Ophthalmology. 1995;102(10):1547-1554. doi:10.1016/S0161-6420(95)30848-2
Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea. 2001;20(1):1-13. doi:10.1097/00003226-200101000-00001
Schwartz GS, Holland EJ. Oral acyclovir for the management of herpes simplex virus keratitis in children. Am J Ophthalmol. 2000;129(2):175-180. doi:10.1016/S0002-9394(99)00312-9
Akova YA, Onat M, Sener EC, Eroğlu A. Bilateral herpetic keratitis: clinical characteristics and risk factors. Cornea. 2001;20(1):28-32. doi:10.1097/00003226-200101000-00006
Akova YA, Onat M, Sener EC, Eroğlu A. Bilateral herpetic keratitis: clinical characteristics and risk factors. Cornea. 2001;20(1):28-32. doi:10.1097/00003226-200101000-00006
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185-191. doi:10.2147/OPTH.S80475
Akova YA, Onat M, Sener EC, Eroğlu A. Bilateral herpetic keratitis: clinical characteristics and risk factors. Cornea. 2001;20(1):28-32. doi:10.1097/00003226-200101000-00006
Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387(10023):1109-1122. doi:10.1016/S0140-6736(15)00149-X
Azher TN, Yin XT, Tajfirouz D, Huang AJW, Stuart PM. Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol. 2017;11:185-191. doi:10.2147/OPTH.S80475
Akova YA, Onat M, Sener EC, Eroğlu A. Bilateral herpetic keratitis: clinical characteristics and risk factors. Cornea. 2001;20(1):28-32. doi:10.1097/00003226-200101000-00006
Johnston C, Corey L. Current concepts for genital herpes simplex virus infection: diagnostics and pathogenesis of genital tract shedding. Clin Microbiol Rev. 2016;29(1):149-161. doi:10.1128/CMR.00043-15
Herpetic Eye Disease Study Group. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med. 1998;339(5):300-306. doi:10.1056/NEJM199807303390503
Herpetic Eye Disease Study Group. Risk factors for recurrence of herpes simplex virus eye disease. Arch Ophthalmol. 2000;118(8):1030-1036. doi:10.1001/archopht.118.8.1030
Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus stromal keratitis. Ophthalmology. 2015;122(1):1-9. doi:10.1016/j.ophtha.2014.09.021
Woodward DF, Krauss AH, Chen J, Lai RK, Spada CS, Burk RM, et al. The pharmacology of prostaglandin F2α analogs in the eye. Surv Ophthalmol. 2007;52(Suppl 2):S1-S2. doi:10.1016/j.survophthal.2007.08.002
Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986-1000. doi:10.1161/ATVBAHA.110.207449
Wand M, Gilbert CM, Liesegang TJ. Latanoprost and herpes simplex keratitis. Am J Ophthalmol. 1999;127(5):602-604. doi:10.1016/S0002-9394(98)00429-2
Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017;17(4):233-247. doi:10.1038/nri.2017.1
O’Brien TP, Maguire MG, Fink NE, Alfonso E, McDonnell P. Epithelial healing in herpes simplex virus keratitis: factors associated with delayed healing. Ophthalmology. 1995;102(10):1547-1554. doi:10.1016/S0161-6420(95)30848-2
Kaye SB, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25(4):355-380. doi:10.1016/j.preteyeres.2006.05.001
Dhaliwal DK, Romanowski EG, Yates KA, Gordon YJ. Experimental reactivation of ocular herpes simplex virus type 1 by laser in a rabbit model. Ophthalmology. 1999;106(10):1926-1930. doi:10.1016/S0161-6420(99)90405-3
Nagy ZZ, McDonnell PJ. Herpes simplex keratitis after excimer laser refractive surgery. Ophthalmology. 1999;106(8):1400-1404. doi:10.1016/S0161-6420(99)90352-7
Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea. 2001;20(1):1-13. doi:10.1097/00003226-200101000-00001
Wilhelmus KR. Diagnosis and management of herpes simplex stromal keratitis. Cornea. 2007;26(9 Suppl 1):S12-S19. doi:10.1097/ICO.0b013e318157a6c1
Herpetic Eye Disease Study Group. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med. 1998;339(5):300-306. doi:10.1056/NEJM199807303390503
