Clinical Manifestations and Outcomes of Treatment in Cytomegalovirus Endotheliitis

Young-Jun Kim; Woong-Sun Yoo; Yong-Seop Han; Inyoung Chung; Seong-Wook Seo; Ji-Myong Yoo; Jong-Moon Park; Min-Chul Cho; Seong-Jae Kim

doi:10.3341/jkos.2016.57.6.863

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Kim, Yoo, Han, Chung, Seo, Yoo, Park, Cho, and Kim: Clinical Manifestations and Outcomes of Treatment in Cytomegalovirus Endotheliitis

Original Article

J Korean Ophthalmol Soc 2016;57(6):863-875.

Published online: 25 September 2016

DOI: https://doi.org/10.3341/jkos.2016.57.6.863

Clinical Manifestations and Outcomes of Treatment in Cytomegalovirus Endotheliitis

Young-Jun Kim, MD¹, Woong-Sun Yoo, MD², Yong-Seop Han, MD, PhD^1,³, Inyoung Chung, MD, PhD^1,³, Seong-Wook Seo, MD, PhD^1,³, Ji-Myong Yoo, MD, PhD^1,³, Jong-Moon Park, MD, PhD^1,³, Min-Chul Cho, MD⁴, Seong-Jae Kim, MD, PhD^1,³

¹Department of Ophthalmology, Gyeongsang National University School of Medicine, Jinju, Korea

²Lee Seong Su Eye Center, Jinju, Korea

³Gyeongsang Institute of Health Science, Gyeongsang National University, Jinju, Korea

⁴Department 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

Received 14 January 2016 Revised 18 April 2016 Accepted 24 May 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.

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Keywords: Cytomegalovirus, Endotheliitis, Ganciclovir

References

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Figure 1.

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.

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Figure 2.

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.

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Figure 3.

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.

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Figure 4.

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.

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Figure 5.

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.

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Figure 6.

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.

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Figure 7.

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.

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Table 1.

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.

Table 2.

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.

Table 3.

Changes of visual acuity and intraocular pressure

Pt.	BCVA (log MAR)		IOP (mm Hg)		ECC (/mm³)		CCT (μm)
Pt.	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.

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