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Diagnosis and Management of CMV Endotheliitis

  • Ashish Kumar
  • Jodhbir Singh MehtaEmail author
Ocular Microbiology and Immunology (B Jeng and L Schocket, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Ocular Microbiology and Immunology

Abstract

Purpose of Review

The purpose of this review is to elucidate the recent developments in the diagnostic armamentarium and the treatment strategy of CMV endotheliitis.

Recent Findings

CMV endotheliitis is now increasingly recognized entity especially in the Asian population. The exact pathogenesis is still unknown but many risk factors have been identified. A strong suspicion based on clinical features with the use of modern diagnostic tools like PCR and high resolution imaging modalities can lead to early confirmation of the disease. Early diagnosis and appropriate treatment at the initial stage are crucial to avoid the sequelae.

Summary

Apart from the typical clinical features, any patient presenting with KPs, raised IOP with mild AC reaction especially following corneal transplant, diagnosis of CMV endotheliitis should be considered. CMV endotheliitis can mimic graft rejection. PCR can help confirm but clinical acumen still remains the mainstay tool for diagnosis. Oral valganciclovir is the definitive treatment till date but recurrences are common. Future studies to find the appropriate dosage, duration, and the route of ganciclovir administration for prophylaxis are needed.

Keywords

Cytomegalovirus Endotheliitis Valganciclovir Graft rejection Anterior uveitis PCR 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Human and Animal Rights

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 2010;20:202–13.Google Scholar
  2. 2.
    De Schryver I, Rozenberg F, Cassoux N, Sotozono C, Inatomi T, Mochida C, et al. Diagnosis and treatment of cytomegalovirus iridocyclitis without retinal necrosis. Br J Ophthalmol. 2006;90(7):852–5.Google Scholar
  3. 3.
    Teoh SB, Thean L, Koay E. Cytomegalovirus in aetiology of Posner-Schlossman syndrome: evidence from quantitative polymerase chain reaction. Eye (Lond). 2005;19(12):1338–40.Google Scholar
  4. 4.
    Bloch-Michel E, Dussaix E, Cerqueti P, Patarin D. Possible role of cytomegalovirus infection in the etiology of the Posner-Schlossmann syndrome. Int Ophthalmol. 1987;11(2):95–6.Google Scholar
  5. 5.
    Chee SP, Bacsal K, Jap A, Se-Thoe SY, Cheng CL, Tan BH. Clinical features of cytomegalovirus anterior uveitis in immunocompetent patients. Am J Ophthalmol. 2008;145(5):834–40.Google Scholar
  6. 6.
    Van Boxtel LA, Van Der Lelij A, Van Der Meer J, Los LI. Cytomegalovirus as a cause of anterior uveitis in immunocompetent patients. Ophthalmology. 2007;114(7):1358–62.Google Scholar
  7. 7.
    Park SW, Hg YU. Association of cytomegalovirus with idiopathic chronic anterior uveitis with ocular hypertension in Korean patients. Ocul Immunol Inflamm. 2013;21(3):192–6.Google Scholar
  8. 8.
    Chen SC, Chuang CT, Chu MY, Sheu SJ. Patterns and etiologies of uveitis at a tertiary referral center in Taiwan. Ocul Immunol Inflamm. 2017;25(sup1):S1–S38.Google Scholar
  9. 9.
    Tan WJ, Poh EW, Wong PY, Ho SL, Lim WK, Teoh SC. Trends in patterns of anterior uveitis in a tertiary institution in Singapore. Ocul Immunol Inflamm. 2013;21(4):270–5.Google Scholar
  10. 10.
    Hwang YS, Shen CR, Chang SH, Lai CC, Liu CL, Chen KJ, et al. The validity of clinical feature profiles for cytomegaloviral anterior segment infection. Graefes Arch Clin Exp Ophthalmol. 2011;249(1):103–10.Google Scholar
  11. 11.
    Woo JH, Lim WK, Ho SL, Teoh SC. Characteristics of cytomegalovirus uveitis in immunocompetent patients. Ocul Immunol Inflamm. 2015;23(5):378–83.Google Scholar
  12. 12.
    Kongyai N, Sirirungsi W, Pathanapitoon K, Lai CC, Liu CL, Chen KJ, et al. Viral causes of unexplained anterior uveitis in Thailand. Eye (Lond). 2012;26(4):529–34.Google Scholar
  13. 13.
    Babu K, Kini R, Philips M, Subbakrishna DK. Clinical profile of isolated viral anterior uveitis in a south Indian patient population. Ocul Immunol Inflamm. 2014;22(5):356–9.Google Scholar
  14. 14.
    Yamauchi Y, Suzuki J, Sakai J, Sakamoto S, Iwasaki T, Usui M. A case of hypertensive keratouveitis with endotheliitis associated with cytomegalovirus. Ocul Immunol Inflamm. 2007;15(5):399–401.Google Scholar
  15. 15.
    Kandori M, Miyazaki D, Yakura K, Lai CC, Liu CL, Chen KJ, et al. Relationship between the number of cytomegalovirus in anterior chamber and severity of anterior segment inflammation. Jpn J Ophthalmol. 2013;57(6):497–502.Google Scholar
  16. 16.
    Markomichelakis NN, Canakis C, Zafirakis P, Marakis T, Mallias I, Theodossiadis G. Cytomegalovirus as a cause of anterior uveitis with sectoral iris atrophy. Ophthalmology. 2002;109(5):879–82.Google Scholar
  17. 17.
    Accorinti M, Gilardi M, Pirraglia MP, Lai CC, Liu CL, Chen KJ, et al. Cytomegalovirus anterior uveitis: long-term follow-up of immunocompetent patients. Graefes Arch Clin Exp Ophthalmol. 2014;252(11):1817–24.Google Scholar
  18. 18.
    Hedayatfar A, Chee SP. Posner-Schlossman syndrome associated with cytomegalovirus infection: a case series from a non-endemic area. Int Ophthalmol. 2014;34(5):1123–9.Google Scholar
  19. 19.
    Khodadoust AA, Attarzadeh A. Presumed autoimmune corneal endotheliopathy. Am J Ophthalmol. 1982;93:718–22.Google Scholar
  20. 20.
    Ohashi Y, Kinoshita S, Mano T, Kiritoshi A, Ohji M. Idiopathic corneal endotheliopathy: a report of two cases. Arch Ophthalmol. 1985;103:1666–8.Google Scholar
  21. 21.
    Maudgal PC, Missotten L, De Clercq E, Descamps J. Varicella- zoster virus in the human corneal endothelium: a case report. Bull Soc Belge Ophtalmol. 1980;190:71–86.Google Scholar
  22. 22.
    Ohashi Y, Yamamoto S, Nishida K, Okamoto S, Kinoshita S, Hayashi K, et al. Demonstration of herpes simplex virus DNA in idiopathic corneal endotheliopathy. Am J Ophthalmol. 1991;112:419–23.Google Scholar
  23. 23.
    Robin JB, Steigner JB, Kaufman HE. Progressive herpetic corneal endotheliitis. Am J Ophthalmol. 1985;100:336–7.Google Scholar
  24. 24.
    Mimura T, Amano S, Nagahara M, Oshika T, Tsushima K, Nakanishi N, et al. Corneal endotheliitis and idiopathic sudden sensorineural hearing loss. Am J Ophthalmol. 2002;133:699–700.Google Scholar
  25. 25.
    Amano S, Oshika T, Kaji Y, Numaga J, Matsubara M, Araie M. Herpes simplex virus in the trabeculum of an eye with corneal endotheliitis. Am J Ophthalmol. 1999;127:721–2.Google Scholar
  26. 26.
    Cheng CK, Chang SW, Hu FR. Acyclovir treatment for linear endotheliitis on grafted corneas. Cornea. 1995;14:311–5.Google Scholar
  27. 27.
    Koizumi N, Yamasaki K, Kawasaki S, Sotozono C, Inatomi T, Mochida C, et al. Cytomegalovirus in aqueous humour from an eye with corneal endotheliitis. Am J Ophthalmol. 2006;141:564–5.Google Scholar
  28. 28.
    Chee SP, Bacsal K, Jap A, Se-Thoe SY, Cheng CL, Tan BH. Corneal endotheliitis associated with evidence of cytomegalovirus infection. Ophthalmology. 2007;114:798–803.Google Scholar
  29. 29.
    Kam KW, Leung KS, Kwok RP, Yu M, Li FCH, Young AL, et al. Clinical features, diagnosis and treatment outcomes of cytomegalovirus endotheliitis in Hong Kong. Acta Ophthalmol. 2018;96(4):541–2.Google Scholar
  30. 30.
    •• Koizumi N, Inatomi T, Suzuki T, Shiraishi A, Ohashi Y, Kandori M, et al. Clinical features and management of cytomegalovirus corneal endotheliitis: analysis of 106 cases from the Japan corneal endotheliitis study. Br J Ophthalmol. 2014;99(1):54–8. This is the largest case series on CMV endotheliitis which described the clinical characteristics and the treatment regimen used in 109 eyes of 106 patients. The study revealed male predominance (80.2%), topical steroids as an important risk factor (96.3%), coin-shaped and linear KPs as a typical features, and ocular hypertension and anterior uveitis as atypical features of CMV endotheliitis. The findings suggested the effectiveness of the anti-viral treatment and didn’t find any significant differences between the combination (systemic and topical) versus either alone. Google Scholar
  31. 31.
    Jap A, Chee S. Cytomegalovirus-associated anterior segment infection. Exp Rev Ophthalmol. 2011;6(5):517–28.Google Scholar
  32. 32.
    Koizumi N, Suzuki T, Uno T, Chihara H, Shiraishi A, Hara Y, et al. Cytomegalovirus as an etiologic factor in corneal endotheliitis. Ophthalmology. 2008;115:292–7.Google Scholar
  33. 33.
    Kasetsuwan N, Tangmonkongvoragul C. Concomitant herpes simplex virus and cytomegalovirus endotheliitis in immunocompetent patient. BMJ Case Rep. 2013;2013:bcr2012007942.Google Scholar
  34. 34.
    Choi WS, Cho JH, Kim HK, Kim HS, Shin YJ. A case of CMV endotheliitis treated with intravitreal ganciclovir injection. Korean J Ophthalmol. 2013;27:130–2.Google Scholar
  35. 35.
    Su CC, Wang IJ, Chen WL, Lin CP, His B, Hu FR. Topical ganciclovir treatment in patients with cytomegalovirus endotheliitis receiving penetrating keratoplasty. Clin Exp Ophthalmol. 2013;41:339–47.Google Scholar
  36. 36.
    • Anshu A, Chee SP, Mehta JS, Tan DTH. Cytomegalovirus endotheliitis in Descemet’s stripping endothelial keratoplasty. Ophthalmology. 2009;116(4):624–30. This study reported 4 cases of undiagnosed CMV endotheliitis leading to corneal decompensation which ended up with DSAEK. The authors suggested excluding CMV endotheliitis as a cause for endothelial decompensation or sudden loss of ECC post DSAEK. Allograft rejection should be differentiated from CMV endotheliitis. Google Scholar
  37. 37.
    Chee SP, Jap A. Immune ring formation associated with cytomegalovirus endotheliitis. Am J Ophthalmol. 2011;152(3):449–53.Google Scholar
  38. 38.
    Chee SP, Jap A. Presumed Fuchs heterochromic iridocyclitis and Posner–Schlossman syndrome: comparison of cytomegalovirus-positive and negative eyes. Am J Ophthalmol. 2008;146(6):883–9.Google Scholar
  39. 39.
    Lafemina RL, Hayward GS. Differences in cell type-specific blocks to immediate early gene-expression and DNA-replication of human, simian and murine cytomegalovirus. J Gen Virol. 1988;69:355–74.Google Scholar
  40. 40.
    Tang QY, Maul GG. Mouse cytomegalovirus crosses the species barrier with help from a few human cytomegalovirus proteins. J Virol. 2006;80:7510–21.Google Scholar
  41. 41.
    Lilja AE, Shenk T. Efficient replication of rhesus cytomegalovirus variants in multiple rhesus and human cell types. Proc Natl Acad Sci. 2008;105:19950–5.Google Scholar
  42. 42.
    Hudson JB. The murine cytomegalovirus as a model for the study of viral pathogenesis and persistent infections. Arch Virol. 1979;62:1–29.Google Scholar
  43. 43.
    Dogra P, Sparer TE. What we have learned from animal models of hcmv. Methods Mol Biol. 2014;1119:267–88.Google Scholar
  44. 44.
    Sinclair J, Reeves M. The intimate relationship between human cytomegalovirus and the dendritic cell lineage. Front Microbiol. 2014;5.Google Scholar
  45. 45.
    Hosogai M, Shima N, Nakatani Y, Inoue T, Iso T, Yokoo H, et al. Analysis of human cytomegalovirus replication in primary cultured human corneal endothelial cells. Br J Ophthalmol. 2015;99(11):1583–90.Google Scholar
  46. 46.
    Shiraishi A, Hara Y, Takahashi M, Oka N, Yamaguchi M, Suzuki T, et al. Demonstration of “Owl’s eye” morphology by confocal microscopy in a patient with presumed cytomegalovirus corneal endotheliitis. Am J Ophthalmol. 2007;143(4):715–7.Google Scholar
  47. 47.
    Miyanaga M, Sugita S, Shimizu N, Morio T, Miyata K, Maruyama K, et al. A significant association of viral loads with corneal endothelial cell damage in cytomegalovirus anterior uveitis. Br J Ophthalmol. 2009;94(3):336–40.Google Scholar
  48. 48.
    Miyazaki D, Uotani R, Inoue M, Haruki T, Shimizu Y, Yakura K, et al. Corneal endothelial cells activate innate and acquired arm of anti-viral responses after cytomegalovirus infection. Exp Eye Res. 2017;161:143–52.Google Scholar
  49. 49.
    Chee SP, Jap A. Treatment outcome and risk factors for visual loss in cytomegalovirus endotheliitis. Graefes Arch Clin Exp Ophthalmol. 2012;250:383–9.Google Scholar
  50. 50.
    Choi JA, Kim KS, Jung Y, Park HY, Park CK. Cytomegalovirus as a cause of hypertensive anterior uveitis in immunocompetent patients. J Ophthalmic Inflamm Infect. 2016;6(1):32.Google Scholar
  51. 51.
    Su CC, Hu FR, Wang TH, Huang JY, Yeh PT, Lin CP, et al. Clinical outcomes in cytomegalovirus-positive Posner-Schlossman syndrome patients treated with topical ganciclovir therapy. Am J Ophthalmol. 2014;158:1024.e2–31.e2.Google Scholar
  52. 52.
    Chan NS, Chee SP, Caspers L, Bodaghi B. Clinical features of CMV- associated anterior uveitis. Ocul Immunol Inflamm. 2018;26:107–15.Google Scholar
  53. 53.
    Choi JA, Kim JE, Noh SJ, Kyoung KE, Park CK, Paik SY. Enhanced cytomegalovirus infection in human trabecular meshwork cells and its implication in glaucoma pathogenesis. Sci Rep. 2017;7:43349.Google Scholar
  54. 54.
    Jap A, Chee SP. Viral anterior uveitis. Curr Opin Ophthalmol. 2011;22:483–8.Google Scholar
  55. 55.
    Keorochana N, Choontanom R. Efficacy and safety of an extemporaneous preparation of 2% ganciclovir eye drops in CMV anterior uveitis. BMJ Open Ophthalmol. 2017;2(1):e000061.Google Scholar
  56. 56.
    •• Kitazawa K, Jongkhajornpong P, Inatomi T, Koizumi N, Kayukawa K, Wakimasu K, et al. Topical ganciclovir treatment post-Descemet’s stripping automated endothelial keratoplasty for patients with bullous keratopathy induced by cytomegalovirus. Br J Ophthalmol. 2018;102(9):1293–7. This was a prospective case series where continuous application of 0.5% of topical ganciclovir was found to be effective for preventing the recurrence of CMV endotheliitis during the mean follow-up of 40 months in post DSAEK eyes. Google Scholar
  57. 57.
    Shahrudin NA, Mohd Zahidin AZ, Md Noh UK, Wan Abdul Halim WH, Md Din N. CMV endotheliitis: a cause for recurrent failed corneal transplant. GMS Ophthalmol Cases. 2017;7:Doc31.  https://doi.org/10.3205/oc000082.Google Scholar
  58. 58.
    Siak J, Chee SP. Cytomegalovirus anterior uveitis following topical cyclosporine A. Ocul Immunol Inflamm. 2018;26:90–3.Google Scholar
  59. 59.
    Chee SP, Jap A. Cytomegalovirus anterior uveitis: outcome of treatment. Br J Ophthalmol. 2010;94:1648–52.Google Scholar
  60. 60.
    Fan NW, Chung YC, Liu YC, Liu CJ, Kuo YS, Lin PY, et al. Long-term topical ganciclovir and corticosteroids preserve corneal endothelial function in cytomegalovirus corneal endotheliitis. Cornea. 2016;35:596–601.Google Scholar
  61. 61.
    Kobayashi A, Yokogawa H, Higashide T, Nitta K, Sugiyama K. Clinical significance of owl eye morphologic features by in vivo laser confocal microscopy in patients with cytomegalovirus corneal endotheliitis. Am J Ophthalmol. 2012;153:445–53.Google Scholar
  62. 62.
    Wong VW, Chan CK, Leung DY, Lai TY. Long-term results of oral valganciclovir for treatment of anterior segment inflammation secondary to cytomegalovirus infection. Clin Ophthalmol. 2012;6:595–600.Google Scholar
  63. 63.
    Yokogawa H, Kobayashi A, Sugiyama K. Mapping owl’s eye cells of patients with cytomegalovirus corneal endotheliitis using in vivo laser confocal microscopy. Jpn J Ophthalmol. 2013;57:80–4.Google Scholar
  64. 64.
    Kandori M, Inoue T, Takamatsu F, Kojima Y, Hori Y, Maeda N, et al. Prevalence and features of keratitis with quantitative polymerase chain reaction positive for cytomegalovirus. Ophthalmology. 2010;117:216–22.Google Scholar
  65. 65.
    Kawaguchi T, Sugita S, Shimizu N, Mochizuki M. Kinetics of aqueous flare, intraocular pressure and virus-DNA copies in a patient with cytomegalovirus iridocyclitis without retinitis. Int Ophthalmol. 2007;27:383–6.Google Scholar
  66. 66.
    Wong JX, Agrawal R, Wong EP, Teoh SC. Efficacy and safety of topical ganciclovir in the management of cytomegalovirus (CMV) related anterior uveitis. J Ophthalmic Inflamm Infect. 2016;6:10.Google Scholar
  67. 67.
    Shimazaki J, Harashima A, Tanaka Y. Corneal endotheliitis with cytomegalovirus infection of corneal stroma. Eye (Lond). 2010;24:1105–7.Google Scholar
  68. 68.
    Alfawaz A. Cytomegalovirus-related corneal endotheliitis: a review article. Saudi J Ophthalmol. 2013;27:47–9.Google Scholar
  69. 69.
    Jhanji V, Kwok R, Young AL. Eighteen months of anterior chamber inflammation. BMJ Case Rep. 2013; 2013.Google Scholar
  70. 70.
    Inoue Y. Review of clinical and basic approaches to corneal endotheliitis. Cornea. 2014;33(Suppl 11):S3–8.Google Scholar
  71. 71.
    Martin Ramirez A, Cardenoso Domingo L, Gonzalez Guijarro JJ. PCR multiplex for CMV detection in patients with anterior uveitis. Ocul Immunol Inflamm. 2018:1–6.Google Scholar
  72. 72.
    Joye A, Gonzales J. Ocular manifestations of cytomegalovirus in immunocompetent hosts. Curr Opin Ophthalmol. 2018;29(6):535–42.Google Scholar
  73. 73.
    Takase H, Kubono R, Terada Y, Imai A, Fukuda S, Tomita M, et al. Comparison of the ocular characteristics of anterior uveitis caused by herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Jpn J Ophthalmol. 2014;58(6):473–82.Google Scholar
  74. 74.
    Sugita S, Ogawa M, Shimizu N, Morio T, Ohguro N, Nakai K, et al. Use of a comprehensive polymerase chain reaction system for diagnosis of ocular infectious diseases. Ophthalmology. 2013;120:1761–8.Google Scholar
  75. 75.
    Miyazaki D, Shimizu D, Shimizu Y, Inoue Y, Inoue T, Higaki S, et al. Diagnostic efficacy of real-time PCR for ocular cytomegalovirus infections. Graefes Arch Clin Exp Ophthalmol. 2018;256(12):2413–20.Google Scholar
  76. 76.
    Carmichael A. Cytomegalovirus and the eye. Eye. 2011;26(2):237–40.Google Scholar
  77. 77.
    De Groot-Mijnes JD, Rothova A, Van Loon AM, et al. Polymerase chain reaction and Goldmann-Witmer coefficient analysis are complimentary for the diagnosis of infec- tious uveitis. Am J Ophthalmol. 2006;141(2):313–8.Google Scholar
  78. 78.
    Relvas L, Antoun J, de Groot-Mijnes JDF, Motulsky E, Ten Dam-Van Loon N, Makhoul D, et al. Diagnosis of cytomegalovirus anterior uveitis in two European referral centers. Ocul Immunol Inflamm. 2018;26(1):116–21.Google Scholar
  79. 79.
    Chu H, Sun C, Chuang W, Liou S, Ma D, Lai C, et al. Cytomegalovirus associated corneal endotheliitis after penetrating keratoplasty in a patient with Fuchs corneal endothelial dystrophy. Br J Ophthalmol. 2010;96(2):300–1.Google Scholar
  80. 80.
    Sonoyama H, Araki-Sasaki K, Osakabe Y, Nakamura M, Amano S, Koizumi N, et al. Detection of cytomegalovirus DNA from cytomegalovirus corneal endotheliitis after penetrating keratoplasty. Cornea. 2010;29(6):683–5.Google Scholar
  81. 81.
    • Ang M, Sng C, Chee S, Tan D, Mehta J. Outcomes of corneal transplantation for irreversible corneal decompensation secondary to corneal endotheliitis in asian Eyes. Am J Ophthalmol. 2013;156(2):260–266.e2. This study highlighted the importance of CMV aqueous PCR analysis before corneal transplantation. Patients with positive CMV PCR preoperatively were more likely to have recurrence, despite anti-CMV treatment before surgery. Google Scholar
  82. 82.
    Fernández López E, Chan E. Descemet stripping automated endothelial keratoplasty outcomes in patients with cytomegalovirus endotheliitis. Cornea. 2017;36(1):108–12.Google Scholar
  83. 83.
    •• Tan TE, Tan DTH. Cytomegalovirus corneal endotheliitis after Descemet membrane endothelial keratoplasty. Cornea. 2018;00:1–6. This is the first case series of CMV endotheliitis after DMEK. The authors highlighted the importance of high index of suspicion of CMV endotheliitis which can present as allograft rejection after DMEK. PCR is advised for prompt diagnosis. Early diagnosis and appropriate treatment will improve the outcome. Google Scholar
  84. 84.
    Chee S, Jap A, Wen Ling E, Ti S. Cytomegalovirus positive corneal stromal edema with keratic precipitates after penetrating keratoplasty. Cornea. 2013;32(8):1094–8.Google Scholar
  85. 85.
    Li J, Terry M, Goshe J, Shamie N, Davis-Boozer D. Graft rejection after Descemet's stripping automated endothelial keratoplasty. Ophthalmology. 2012;119(1):90–4.Google Scholar
  86. 86.
    Hos D, Tuac O, Schaub F, Stanzel T, Schrittenlocher S, Hellmich M, et al. Incidence and clinical course of immune reactions after Descemet membrane endothelial keratoplasty. Ophthalmology. 2017;124(4):512–8.Google Scholar
  87. 87.
    Ham L, Dapena I, Liarakos V, Baydoun L, van Dijk K, Ilyas A, et al. Midterm results of Descemet membrane endothelial keratoplasty: 4 to 7 years clinical outcome. Am J Ophthalmol. 2016;171:113–21.Google Scholar
  88. 88.
    •• da Costa Paula C, Gore D, Shah K, Kuit G, Angunawela R, Barnett J, et al. Cytomegalovirus infection is not a major cause of corneal graft failure in the United Kingdom. Eye (Lond). 2019.  https://doi.org/10.1038/s41433-018-0331-9. The authors looked for the presence of CMV DNA in the failed cornea graft and the donor corneal rims. No CMV could be identified and they concluded that CMV is not a significant risk factor for graft failure in UK and so do not suggest the change in the current practice patter where aqueous PCR analysis for CMV is not routinely done in UK.
  89. 89.
    Kobayashi R, Hashida N, Soma T, Koh S, Miki A, Usui S, et al. Clinical findings of anterior segment spectral domain optical coherence tomography images in cytomegalovirus corneal endotheliitis. Cornea. 2017;36(4):411–4.Google Scholar
  90. 90.
    • Chan A, Mehta J, Al Jajeh I, Iqbal J, Anshu A, Tan D. Histological features of cytomegalovirus-related corneal graft infections, its associated features and clinical significance. Br J Ophthalmol. 2015;100(5):601–6. This was a retrospective histological study of 48 cases of failed repeat penetrating keratoplasty. 3/48 cases was CMV positive. They reported that CMV infection was not just confined to endothelium but extended into corneal stroma which may act as a potential reservoir for graft infection especially in repeat partial thickness endothelial keratoplasty. Google Scholar
  91. 91.
    Åsberg A, Humar A, Rollag H, Jardine A, Kumar D, Aukrust P, et al. Lessons learned from a randomized study of oral valganciclovir versus parenteral ganciclovir treatment of cytomegalovirus disease in solid organ transplant recipients: the VICTOR trial. Clin Infect Dis. 2016;62(9):1154–60.Google Scholar
  92. 92.
    • Waduthantri S, Zhou L, Chee S. Intra-cameral level of ganciclovir gel, 0.15% following topical application for cytomegalovirus anterior segment infection: a pilot study. PLoS One. 2018;13(1):e0191850. This study showed that the intracameral levels of ganciclovir after topical application of 0.15% ganciclovir gel after 6 weeks was much below the level of 50% of inhibitory dose for CMV replication. Even with the subtherapeutic levels in aqueous, there was an effective clearance of CMV from the aqueous due to preferential distribution of ganciclovir in the eye. Google Scholar
  93. 93.
    Suzuki T, Ohashi Y. Corneal endotheliitis. Semin Ophthalmol. 2008;23(4):235–40.Google Scholar
  94. 94.
    Mietz H, Aisenbrey S, Bartz-Schmidt K, Bamborschke S, Krieglstein G. Ganciclovir for the treatment of anterior uveitis. Graefes Arch Clin Exp Ophthalmol. 2000;238(11):905–9.Google Scholar
  95. 95.
    Hsiao C, Hwang Y, Chuang W, Ma D, Yeh L, Chen S, et al. Prevalence and clinical consequences of cytomegalovirus DNA in the aqueous humour and corneal transplants. Br J Ophthalmol. 2018:bjophthalmol-2018-312196.  https://doi.org/10.1136/bjophthalmol-2018-312196.
  96. 96.
    •• Basilious A, Chew H. Topical ganciclovir for prophylaxis of cytomegalovirus endotheliitis in endothelial keratoplasty. Cornea. 2019;38(1):120–2. This study showed the effectiveness of long term application of topical ganciclovir 0.15% gel to prevent the recurrence of CMV associated graft failure in a mean follow-up duration of around 2 years. Google Scholar

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Authors and Affiliations

  1. 1.Singapore National Eye CentreSingaporeSingapore
  2. 2.Aravind Eye Care SystemMaduraiIndia
  3. 3.Tissue Engineering and Stem Cell GroupSingapore Eye Research InstituteSingaporeSingapore
  4. 4.Eye-ACPDuke-NUS Graduate Medical SchoolSingaporeSingapore
  5. 5.Department of Ophthalmology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  6. 6.School of Material Science and EngineeringNanyang Technological UniversitySingaporeSingapore

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