JKOS Journal of the Korean Ophthalmological Society J Korean Ophthalmol Soc 0378-6471 2092-9374 Korean Ophthalmological Society 10.3341/jkos.2016.57.6.863 jkos-57-863 Original Article Clinical Manifestations and Outcomes of Treatment in Cytomegalovirus Endotheliitis KimYoung-Jun MD 1 YooWoong-Sun MD 2 HanYong-Seop MD, PhD 1 3 ChungInyoung MD, PhD 1 3 SeoSeong-Wook MD, PhD 1 3 YooJi-Myong MD, PhD 1 3 ParkJong-Moon MD, PhD 1 3 ChoMin-Chul MD 4 KimSeong-Jae MD, PhD 1 3 Department of Ophthalmology, Gyeongsang National University School of Medicine, Jinju, Korea Lee Seong Su Eye Center, Jinju, Korea Gyeongsang Institute of Health Science, Gyeongsang National University, Jinju, Korea Department of Laboratory Medicine, Gyeongsang National University College of Medicine, Jinju, Korea Address reprint requests to Seong-Jae Kim, MD, PhD Department of Ophthalmology, Gyeongsang National University Hospital, #79 Gangnam-ro, Jinju 52727, Korea Tel: 82-55-750-8171, Fax: 82-55-758-4158 E-mail: Maya12kim@naver.com 09 2016 25 09 2016 576 863 875 14012016 18042016 24052016 Copyright © 2016 Korean Ophthalmological Society 2016 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Purpose

To elucidate the clinical manifestations of cytomegalovirus (CMV) endotheliitis, and evaluate the outcomes of treatment in CMV endotheliitis.

 Methods

We reviewed the medical records of 7 patients (8 eyes) who were diagnosed with CMV endotheliitis via a polymerase chain reaction (PCR) of aqueous humor and were treated with ganciclovir.

 Results

Eight eyes of 7 patients were followed for a mean of 17.8 months. One patient had bilateral corneal endotheliitis. All eyes had coin-shaped keratoprecipitates and mild anterior chamber inflammation (1+∼2+). All eyes had an absence of anterior segment inflammation 3 weeks after ganciclovir treatment. Following treatment, the mean visual acuity improved significantly from 0.60 ± 0.40 (log MAR) at baseline to 0.18 ± 0.18 (log MAR) at last follow-up. The mean intraocular pressure (IOP) decreased significantly from 30 mm Hg at baseline to 12 mm Hg at last visit. Two eyes had a recurrence of corneal endotheliitis, where one underwent penetrating keratoplasty and the other was treated with intravitreal ganciclovir injection.

 Conclusions

Patients with increased IOP and coin-shaped keratoprecipitates are suspected to have CMV endotheliitis, and PCR of aqueous humor is needed to diagnose CMV endotheliitis. More than 6 weeks of ganciclovir treatment might be effective for CMV endotheliitis and may help prevent recurrence.

 Cytomegalovirus Endotheliitis Ganciclovir References Suzuki T Ohashi Y Corneal endotheliitis Semin Ophthalmol 2008 2323540 Koizumi N Yamasaki K Kawasaki S Cytomegalovirus in aqueous humor from an eye with corneal endotheliitis Am J Ophthalmol 2006 1415645 Koizumi N Suzuki T Uno T Cytomegalovirus as an etiologic factor in corneal endotheliitis Ophthalmology 2008 1152927.e3 Koizumi N Inatomi T Suzuki T Clinical features and abdominal of cytomegalovirus corneal endotheliitis: analysis of 106 cases from the Japan corneal endotheliitis study Br J Ophthalmol 2015 99548 Choi WS Cho JH Kim HK A case of CMV endotheliitis treated with intravitreal ganciclovir injection Korean J Ophthalmol 2013 271302 Shin SY Kwon KC Park JW Evaluation of the Seeplex(R) Meningitis ACE Detection kit for the detection of 12 common abdominal and viral pathogens of acute meningitis Ann Lab Med 2012 32449 Hwang YS Shen CR Chang SH The validity of clinical abdominal profiles for cytomegaloviral anterior segment infection Graefes Arch Clin Exp Ophthalmol 2011 24910310 Chee SP Jap A Treatment outcome and risk factors for visual loss in Cytomegalovirus endotheliitis Graefes Arch Clin Exp Ophthalmol 2012 2503839 Chee SP Bascal K Jap A Clinical features of cytomeglovirus anterior uveitis in immunocompetent patients Am J Ophthalmol 2008145 83440 Anshu A Chee SP Mehta JS Tan DT Cytomegalovirus endotheliitis in Descemet's stripping endothelial keratoplasty Ophthalmology 2009 11662430 Alfawaz A Cytomegalovirus-related corneal endotheliitis: a abdominal article Saudi J Ophthalmol 2013 27479 Su CC Wang IJ Chen WL Topical ganciclovir treatment in patients with cytomegalovirus endotheliitis receiving penetrating keratoplasty Clin Experiment Ophthalmol 2013 4133947 Figures and Tables

Clinical photographs of patient 1. Slit lamp photograph showed sectorial corneal edema and coin-shaped keratic precipitates in left eye of patient 1 (A, arrow). Specular microscopy revealed pleomorphism and polymegathism of corneal endothelial cells (B). Multiplex polymerase chain reaction showed positive in cytomegalovirus (CMV) (C). After withdrawal of valganciclovir, bullous keratopathy occurred (D). No recurrence had been occurred after penetrating keratoplasty (E). EBV = Epstein-Barr virus; HHV6 = human herpes virus 6; HSV1, 2= herpetic simplex virus 1, 2; VZV = varicella-zoster virus; IC = internal control; NC = negative control; PC = positive control.

Clinical photographs of patient 2. Slit lamp photograph showed sectorial corneal edema and coin-shaped keratic precipitates in right eye (A, arrow) and left eye (B, arrow) of patient 2. Specular microscopy revealed decreased number, pleomorphism and polymegathism of corneal endothelial cells in right (C) and left eyes (D). Multiplex polymerase chain reaction showed positive with cytomegalovirus (CMV) in aqueous humor in both eyes (E). After valganciclovir treatment, keratic precipitates and edema of cornea were disappeared in right (F) and left eye (G). EBV = Epstein-Barr virus; HHV6 = human herpes virus 6; HSV 1, 2 = herpetic simplex virus 1, 2; VZV = Varicella-zoster virus; IC = internal control; PC = positive control; NC = negative control.

Clinical photographs of patient 3. Slit lamp photograph showed sectorial corneal edema and coin-shaped keratic precipitates in right eye (A, arrow) of patient 3. Specular microscopy revealed decreased number and polymegathism of corneal endothelial cells (B). Multiplex polymerase chain reaction showed positive with cytomegalovirus (CMV) in aqueous humor in right eye (C). Corneal lesions were disappeared after ganciclovir treatment (D). HHV6 = human herpes virus 6; EBV = Epstein-Barr virus; HSV1, 2 = herpetic simplex virus 1, 2; VZV = varicella-zoster virus; IC = internal control; PC = positive control; NC = negative control.

Clinical photographs of patient 4. Slit lamp photograph showed sectorial corneal edema and coin-shaped keratic precipitates in left eye (A, arrow) of patient 4. Specular microscopy revealed decreased number, polymegathism, pleomorphism, and hy-po-reflectivity of corneal endothelial cells (B). Multiplex polymerase chain reaction showed positive with cytomegalovirus (CMV) in aqueous humor in left eye (C). Two months after completion of ganciclovir treatment of 6 weeks, coin-shaped keratic precipitates were re-appeared in different location of cornea (D, arrows). Repeated multiplex polymerase chain reaction (PCR) revealed positive with CMV in aqueous humor (E). Corneal keratic precipitates and edema were regressed after intravitreal ganciclovir injection (F). HHV6 = human herpes virus 6; EBV = Epstein-Barr virus; HSV1, 2 = herpetic simplex virus 1, 2; VZV = Varicella-zoster virus; IC = internal control; PC = positive control; NC = negative control.

Clinical photographs of patient 5. Slit lamp photograph showed sectorial corneal edema and coin-shaped keratic precipitates in right eye (A, arrow) of patient 5. Specular microscopy revealed decreased number, polymegathism, and hypo-reflectivity of corneal endothelial cells (B). Multiplex polymerase chain reaction showed positive with cytomegalovirus (CMV) in aqueous humor in right eye (C). After ganciclovir treatment, coin-shaped keratic precipitate was regressed (D). HHV6 = human herpes virus 6; EBV = Epstein-Barr virus; HSV1, 2 = herpetic simplex virus 1, 2; VZV = Varicella-zoster virus; IC = internal control; PC = positive control; NC = negative control.

Clinical photographs of patient 6. Slit lamp photograph showed sectorial corneal edema and coin-shaped keratic precipitates in right eye at superior cornea (A, arrow) of patient 6. Specular microscopy revealed decreased number and polymegathism of corneal endothelial cells (B). Multiplex polymerase chain reaction showed positive with cytomegalovirus (CMV) in aqueous humor in right eye (C). Corneal lesions were disappeared after ganciclovir treatment (D). HHV6 = human herpes virus 6; EBV = Epstein-Barr virus; HSV1, 2 = herpetic simplex virus 1, 2; VZV = Varicella-zoster virus; IC = internal control; PC = positive control; NC = negative control.

Clinical photographs of patinet 7. Slit lamp photograph showed sectorial corneal edema and coin-shaped keratic precipitates in left eye at inferior cornea (A, black and white arrow) of patient 7. Specular microscopy revealed decreased number of corneal endothelial cells (B). Multiplex polymerase chain reaction showed positive with cytomegalovirus (CMV) in aqueous humor in left eye (C). After ganciclovir treatment, lesions of cornea were vanished (D). HHV6 = human herpes virus 6; EBV = Epstein-Barr virus; HSV1, 2 = herpetic simplex virus 1, 2; VZV = Varicella-zoster virus; IC = internal control; PC = positive control; NC = negative control.

Clinical data of patients with CMV endotheliitis

Pt. Sex Age (years) Baseline BCVA (log MAR) Baseline IOP (mm Hg) Baseline ECC (/mm3) Baseline CCT (μm) Coin-shaped KPs CMV IgM/IgG Previous ocular surgery Follow up (months)
1 M 50 0.69 24 614 739 Y −/+ − 31
2 (OD) M 53 0.69 32 802 622 Y −/+ Trab 26
2 (OS) M 53 1.0 38 850 610 Y −/+ Trab, AGV 26
3 M 68 0.22 27 1,149 557 Y −/+ Trab 18
4 M 65 0.22 29 1,348 572 Y   – 18
5 M 52 1.0 26 923 583 Y −/+ – 10
6 M 48 1.0 16 1,196 604 Y   Trab 10
7
 M
 48
 0
 48
 1,758
 602
 Y
  
 –
 3
Mean   54.6 0.60 30 1,067 611.1       17.8

CMV = cytomegalovirus; BCVA = best corrected visual acuity; IOP = intraocular pressure; ECC = endothelial cell count; CCT = central corneal thickness; KP = keratic precipitate; MAR = minimal angle of resolution; Trab = trabeculectomy; AGV = ahmed glaucoma valve implantation.

Course of treatment in patients

Pt. Treatment Recur
1 Oral VGCV 1,800 mg 3 wks (d/t self stop) Y
  → post PKP: oral VGCV 1,800 mg 6 wks + 900 mg 6 wks  
2 (OD) Oral VGCV 1,800 mg 6 wks + 900 mg 6 wks N
2 (OS)   N
3 IV GCV 5 mg/kg 2 wks & oral VGCV 1,800 mg 4 wks + 900 mg 6 wks N
4 Oral VGCV 1,800 mg 3 wks + 900 mg 3 wks Y
  → Intravitreal GCV inj. (2 mg/0.1 mL)  
5 Oral VGCV 1,800 mg 3 wks + 900 mg 3 wks N
6 Oral VGCV 1,800 mg 3 wks + 900 mg 3 wks N
7 Oral VGCV 1,800 mg 3 wks + 900 mg 3 wks N

Recur = recurrence; VGCV = valganciclovir; wks = weeks; PKP = penetrating keratoplasty; GCV = ganciclovir; inj. = injection.

Changes of visual acuity and intraocular pressure

Pt. BCVA (log MAR)
 IOP (mm Hg)
 ECC (/mm3)
 CCT (μm)
Baseline Final Baseline Final Baseline Final Baseline Final
1 0.69 0.30 24 12 614 1,092 739 528
2 (OD) 0.69 0.046 32 12 802 675 622 536
2 (OS) 1.0 0.15 38 15 850 793 610 520
3 0.22 0.046 27 12 1,149 1,164 557 505
4 0.22 0.10 29 15 1,348 1,443 572 525
5 1.0 0.52 26 15 923 826 583 524
6 1.0 0.30 16 5 1,092 1,196 604 520
7
 0
 0
 48
 10
 1,758
 1,750
 602
 531
Mean ± SD
 0.60 ± 0.40
 0.18 ± 0.18
 30.0 ± 9.6
 12.0 ± 3.4
 1,067.0 ± 360.0
 1,117.4 ± 358.8
 611.1 ± 55.9
 523.6 ± 9.3
p-value* 0.006 0.001 0.481 0.002

Values are presented as mean ± SD unless otherwise indicated.

BCVA = best corrected visual acuity; MAR = minimal angle of resolution; IOP = intraocular pressure; ECC = endothelial cell count; CCT = central corneal thickness.

Paired-samples t-test.