Cytomegalovirus as a cause of hypertensive anterior uveitis in immunocompetent patients

Abstract

Background

The aims of this study are to investigate the clinical characteristics of patients with anterior hypertensive uveitis and to compare the characteristics between patients in cytomegalovirus (CMV)-positive and CMV-negative groups in their aqueous humor samples.

Immunocompetent patients (n=42) with a history of chronic and/or recurrent hypertensive anterior uveitis underwent ophthalmic examination and serological tests. Among the 42 patients with hypertensive anterior uveitis, aqueous humor sampling was performed in 21, and they were analyzed for viral deoxyribonucleic acids using the polymerase chain reaction (PCR).

Results

The average age of the 42 patients with hypertensive anterior uveitis was 57.6 years, and 29 (69.0 %) of the subjects were males. Of the patients, 22 (52.4 %) underwent glaucoma surgery, and the average corneal endothelial cell counts were 1908 cells/mm2. Among the 21 patients who underwent an aqueous sampling, 6 were positive for CMV-DNA, while 15 were negative. The frequency of glaucoma surgery was similar between groups (CMV positive vs. CMV negative, 66.0 vs. 66.0 %, P=0.701). However, 66.7 % of the CMV-positive group underwent glaucoma tube shunt surgery, whereas 80 % of the CMV-negative group underwent trabeculectomy or received an ExPRESS glaucoma filtration device (Alcon, Fort Worth, TX) for glaucoma surgery (P=0.095). The corneal endothelial cell counts were significantly lower in the CMV-positive group (CMV positive vs. CMV negative, 1245±560 vs. 1981±387 cells/mm2; P=0.009).

Conclusions

CMV was found to be an etiological factor in patients with hypertensive anterior uveitis in Korea. Special caution is needed for patients with CMV-induced hypertensive anterior uveitis, considering its adverse effect on the corneal endothelium.

Choi et al. Journal of Ophthalmic Inflammation and Infection (2016) 6:32

DOI 10.1186/s12348-016-0100-5

Journal of Ophthalmic Inammation and Infection

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Web End = Cytomegalovirus as a cause of hypertensive anterior uveitis in immunocompetent patients

Jin A Choi1, Kyu Seop Kim2, Younhea Jung2, Hae Young Lopilly Park2 and Chan Kee Park2*

Abstract

Background: The aims of this study are to investigate the clinical characteristics of patients with anterior hypertensive uveitis and to compare the characteristics between patients in cytomegalovirus (CMV)-positive and CMV-negative groups in their aqueous humor samples.

Immunocompetent patients (n = 42) with a history of chronic and/or recurrent hypertensive anterior uveitis underwent ophthalmic examination and serological tests. Among the 42 patients with hypertensive anterior uveitis, aqueous humor sampling was performed in 21, and they were analyzed for viral deoxyribonucleic acids using the polymerase chain reaction (PCR).

Results: The average age of the 42 patients with hypertensive anterior uveitis was 57.6 years, and 29 (69.0 %) of the subjects were males. Of the patients, 22 (52.4 %) underwent glaucoma surgery, and the average corneal endothelial cell counts were 1908 cells/mm2. Among the 21 patients who underwent an aqueous sampling, 6 were positive for CMV-DNA, while 15 were negative. The frequency of glaucoma surgery was similar between groups (CMV positive vs. CMV negative, 66.0 vs. 66.0 %, P = 0.701). However, 66.7 % of the CMV-positive group underwent glaucoma tube shunt surgery, whereas 80 % of the CMV-negative group underwent trabeculectomy or received an ExPRESS glaucoma filtration device (Alcon, Fort Worth, TX) for glaucoma surgery (P = 0.095). The corneal endothelial cell counts were significantly lower in the CMV-positive group (CMV positive vs. CMV negative, 1245 560 vs. 1981 387 cells/mm2;

P = 0.009).

Conclusions: CMV was found to be an etiological factor in patients with hypertensive anterior uveitis in Korea. Special caution is needed for patients with CMV-induced hypertensive anterior uveitis, considering its adverse effect on the corneal endothelium.

Keywords: Glaucoma, Uveitis, Cytomegalovirus, Endothelium, Cornea

Background

Herpes viruses are known to play a role in the idiopathic anterior uveitis associated with ocular hypertension [14].There are three herpes viruses responsible for ocular inflammation; human cytomegalovirus (CMV), herpes simplex virus (HSV)-1, and varicella zoster virus (VZV).CMV has been recognized as a cause of morbidity and mortality, mostly in immunocompromised individuals [3, 4]. Recent reports have shown that CMV infection is

an emerging cause of anterior uveitis associated with ocular hypertension in immunocompetent subjects [1, 2, 5, 6]. CMV is also an important cause of corneal endotheliitis, particularly in Asian populations [712]. However, the pathogenesis of CMV-induced anterior uveitis in immunocompetent patients and the systemic and ocular characteristics of the disease are not well understood.

In the present study, we investigated the clinical characteristics of patients with anterior hypertensive uveitis and compared the ocular and systemic characteristics between CMV-positive and CMV-negative patients in their aqueous humor. Finally, we investigated the factors

* Correspondence: mailto:[email protected]

Web End [email protected]

2Department of Ophthalmology and Visual Science, Seoul St. Marys Hospital, College of Medicine, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul 137-701, Republic of KoreaFull list of author information is available at the end of the article

2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/

Web End =http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Choi et al. Journal of Ophthalmic Inflammation and Infection (2016) 6:32 Page 2 of 7

associated with the corneal endothelial cell loss in the hypertensive anterior uveitis patients.

Methods

This was a retrospective review of patients with anterior hypertensive uveitis who were investigated at Seoul St. Marys Hospital from March 2009 to June 2014. This study was performed according to the tenets of the Declaration of Helsinki, and the study protocol was approved by the institutional review/ethics boards of the Seoul St. Marys Hospital, the Catholic University of Korea (IRB number: KC14RISI0513). All of the patients included in this study met the following criteria: (1) anterior uveitis with keratic precipitates (KPs) and (2) increased intraocular pressure (IOP). Patients with the following were excluded: (1) presence of inflammation in vitreous or retina and (2) presence of corneal endothelial changes for a known cause other than anterior uveitis.

All of the participants underwent a comprehensive ophthalmic examination, including a detailed review of medical and ocular histories, best-corrected visual acuity measurement, slit-lamp biomicroscopy, Goldmann applanation tonometry, specular microscopy using a non-contact specular microscope (Konan Noncon Robo, Konan Medical, Inc., Hyogo, Japan), dilated stereoscopic examination of the optic nerve head and fundus, stereoscopic optic disc photography and red-free retinal nerve fiber layer (RNFL) photography (Nonmyd 7; Kowa Company Ltd., Nagoya, Japan), achromatic automated perimetry using the 242 Swedish Interactive Threshold Algorithm Standard program (Humphrey Visual Field (VF) Analyzer; Carl Zeiss Meditec, Inc., Dublin, CA, USA), and optical coherence tomography scans (Cirrus OCT, Carl Zeiss Meditec) to measure peripapillary RNFL thickness. Peripapillary RNFL thickness was determined three times at 256 points around a set diameter(3.4 mm) circle using the fast RNFL program. Only well-focused, well-centered images without eye movement and a signal strength 7 were used. A global average RNFL thickness provided by the software was used for the analysis. All of the patients underwent a laboratory work-up (including complete blood count, erythrocyte sedimentation rate analysis, white cell count and differential, blood chemistry) and serologic screening for IgM and IgG anti-CMV, HSV, and VZV.

Among the 42 patients with hypertensive anterior uveitis, aqueous sampling was performed in 21. Using a 30-gauge needle, 100 L aqueous humor was aspirated under aseptic conditions and subjected to a polymerase chain reaction (PCR) assay for CMV, HSV1, and HSV2 DNA. DNA was extracted from the aqueous humor samples using a QIAamp DNA minikit (Qiagen, Valencia, CA, USA). Quantitative CMV-DNA PCR testing was performed using an AccuPower CMV Quantitative PCR Kit

(Bioneer, Daejun, Republic of Korea). For HSV PCR, the HSV 1/2 PCR Kit (Bio-Core, Seoul, Republic of Korea) was used.

Glaucoma was defined as having glaucomatous disc appearance (thinning of neuroretinal rim, peripapillary hemorrhage, or localized pallor) associated with a typical reproducible VF defect evident on standard automated perimetry. A glaucomatous VF defect was defined as a glaucoma hemifield test result outside normal limits and the presence of at least three contiguous points in the pattern deviation plot with P values <5 %, with at least one point associated with a P value <1 % on two consecutive reliable VF examinations.

Patients were classified according to the duration of active intraocular inflammation. Patients with at least 3 months of active intraocular inflammation were considered to have chronic uveitis, and other patients to have recurrent episode of acute uveitis, which was normalized between attacks [2]. Glaucoma treatment was started in a step-wise manner; anti-glaucoma medication (beta-blocker, alpha-2 agonists, topical acetazolamide, and prostaglandin), and finally, glaucoma surgery. Glaucoma surgery was chosen among conventional trabeculectomy/ExPRESS glaucoma filtration device (Alcon Laboratories, Fort Worth, TX, USA) or Ahmed glaucoma valve implant (New World Medical, Inc., Rancho Cucamonga, CA, USA) surgery, considering preoperative IOP and severity of glaucomatous optic disc damage.

Statistical analysisFor independent samples, the non-parametric Mann-Whitney U test and the 2 test were used to compare between-group means and percentages. Multivariable analysis was performed using simple and multiple linear regressions for corneal endothelial cell counts according to the presence of CMV-DNA in the aqueous humor. First, we adjusted for age and gender (model 1). Then we adjusted for age, gender, lens status, and history of glaucoma surgery (model 2). A P value <0.05 was considered to statistically significant. All of the statistical analyses were performed using the SPSS software (ver. 14.0 for Windows; SPSS Inc.).

Results

The clinical features of our patients are summarized in Table 1. The average age of the 42 patients with hyper-tensive anterior uveitis was 57.6 years, and 29 (69.0 %) of the subjects were males. In total, 22 (52.4 %) patients underwent glaucoma surgery, and the mean corneal endothelial cell counts were 1908 cells/mm2.

Among the 21 patients who underwent aqueous sampling, six were positive for CMV-DNA, whereas 15 were negative (Table 2). The CMV-positive group was significantly younger and more myopic than the CMV-

Choi et al. Journal of Ophthalmic Inflammation and Infection (2016) 6:32 Page 3 of 7

Table 1 Clinical parameters of 42 patients with hypertensive anterior uveitis

Gender (M/F) 29:13Age (range), years 57.6 (2588) Spherical equivalent, D 2.6 (11.250.00) Glaucoma operation,% 22 (52.4 %) Corneal endothelial cell count, cells/mm2 1908 (6253067) Unilaterality 39 (92.9 %)

KPs at baseline examination 28 (67.8 %) Anterior chamber reaction with 1+ or less 37 (88.1 %) Severe peripheral anterior synechiae 0 (0.0 %)

Typical feature of P-S syndrome 14 (33.3 %)

negative group (CMV positive vs. CMV negative: 47.5 14.8 vs. 67.6 11.8 years, P = 0.006; 3.6 4.2 vs. 0.0 1.6 D, P = 0.031). The frequency of glaucoma surgery was similar between the groups (CMV positive vs. CMV negative, 66.0 vs. 66.0 %, P = 0.701). However, 66.7 % of CMV-positive group had an Ahmed glaucoma valve implanted, whereas 80 % of the CMV-negative group underwent trabeculectomy or use of the ExPRESS glaucoma filtration device (P = 0.095). The corneal endothelial cell counts were significantly lower in the CMV-positive group (CMV positive vs. CMV negative: 1245 560 vs. 1981 387 cells/mm2; P = 0.009).

Table 3 shows the laboratory characteristics of subjects with and without CMV-PCR(+) in the aqueous humor. In the CMV-positive subjects, the percentage of monocytes tended to be lower than in the CMV-negative

Table 2 Comparisons of clinical and immunologic characteristics in subjects with or without CMV in aqueous humorCharacteristics CMV-positive subjects n = 6 CMV-negative subjects n = 15 P value Demographic characteristics

Male, n (%) 6 (100 %) 13 (86.7 %) 0.500 Age, years 47.5 14.8 67.6 11.8 0.006 Ocular characteristics

Initial BCVA 0.65 0.29 0.58 0.29 0.569 Final BCVA 0.47 0.46 0.52 0.30 0.733 Spherical equivalent, D -3.6 4.2 0.0 1.6 0.031 Axial length, mm 25.7 1.5 24.4 0.7 0.053 Glaucoma, n (%) 6 (100 %) 13 (86.7 %) 0.347 Average RNFL thickness, m 66.2 16.7 77.8 19.1 0.132 Corneal endothelial cell count, mm2 1245 560 1981 387 0.009 Unilaterality, n (%) 83.3 80.0 0.684 KPs at baseline examination, n (%) 83.3 73.3 0.550 Presence of PAS, n (%) 4 (66.7 %) 5 (33.3 %) 0.331 Anterior chamber reaction with 1+ or less, n (%) 100.0 92.9 0.714 Lens status, phakic, n (%) 5 (83.3 %) 5 (33.3 %) 0.055 Baseline IOP, mmHg 28.83 8.25 22.73 7.86 0.132 Maximum IOP, mmHg 37.17 8.03 39.53 13.02 0.622 Final IOP, mmHg 13.3 3.44 13.5 5.05 0.950 Number of anti-glaucoma medication, n 2.67 0.81 2.67 0.81 0.970 Course of uveitis 0.544

Chronic, n (%) 4 (66.7 %) 13 (86.7 %)

Recurrent, n (%) 2 (33.3 %) 2 (13.3 %)

Glaucoma operation, n (%) 4 (66.7 %) 10 (66.7 %) 0.701 Choice of glaucoma operation 0.095

Ahmed valve, n (%) 3 (75.0 %) 2 (20.0 %)

Trabeculectomy or ExPRESS , n (%) 1 (25.0 %) 8 (80.0 %)

HSV PCR positivity, n (%) 0 (0.0 %) 1 (6.2 %) 0.727 CMV RQ PCR, copies/mL 46,048.8 91,334.5 Negative n/a

CMV cytomegalovirus, BCVA best-corrected visual acuity, RNFL retinal nerve fiber layer, KP keratic precipitate, PAS peripheral anterior synechiae, n/a not applicable

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Table 3 Comparison of laboratory findings in subjects with or without CMV-PCR (+) in aqueous humorCharacteristics CMV-positive subjects n = 6 CMV-negative subjects n = 15 P value Complete blood count

WBC count, cells/L 7300 900 6,700 1900 0.590 Seg, % 54.4 8.7 55.9 7.7 0.677 Lymp, % 35.0 6.6 31.9 7.1 0.424 Mono, % 6.5 0.7 7.8 1.6 0.055 Eosinophil, % 3.5 1.8 3.8 3.2 0.970 Basophil, % 0.6 0.3 0.5 0.2 0.302 RBC count, 106/L 5.0 0.5 4.4 0.6 0.059 Hemoglobin g/dl 15.5 1.4 13.9 2.0 0.070 Platelet count, 103/L 247.5 51.0 220.8 58.8 0.329 ESR, mm/h 10.5 7.6 31.8 32.7 0.283 Blood chemistry

FBS, mg/dL 103.7 18.7 100.5 44.1 0.519 AST, IU/L 23.3 3.3 23.6 10.5 0.367 ALT, IU/L 28.7 10.5 27.2 15.7 0.590 BUN, mg/dL 15.3 4.7 17.8 6.7 0.261 Creatinine, mg/dL 0.9 0.1 1.0 0.3 0.971 GFR, ml/min/1.73 m2 91.1 8.9 79.2 19.1 0.178 Na, mEq/L 142.3 1.2 141.9 3.2 0.858 K, mEq/L 4.4 0.4 4.3 0.5 0.914 Immunology

HSV IgM positivity, n (%) 1 (16.7 %) 0 (0.0 %) 0.273 HSV IgG, titer, AU/mL 3.3 1.4 6.5 6.8 0.320 VZV IgM positivity, n (%) 1 (16.7 %) 0 (0.0 %) 0.273 VZV IgG titer, AU/mL 5.3 3.1 5.0 2.2 1.000 CMV IgM positivity, n (%) 0 (0.0 %) 0 (0.0 %) n/a CMV IgG titer, AU/mL 54.7 15.3 55.7 16.4 1.000

HSV herpes simplex virus, VZV varicella zoster virus, CMV cytomegalovirus, ESR erythrocyte sedimentation rate, FBS fasting blood sugar, AST aspartate aminotransferase, ALT alanine aminotransferase, BUN blood urea nitrogen, GFR glomerular filtration rate, n/a not applicable

subjects, with marginal significance (P = 0.055), whereas other parameters did not differ between the groups. The presence of CMV in the aqueous humor was significantly associated with corneal endothelial cell count after controlling for age and gender (P = 0.023), which was maintained after additional adjustment for lens status and history of glaucoma surgery (P < 0.001; Table 4). The clinical information of the 6 CMV+ patients was described in the Additional file 1, and two representative cases with antiviral treatment are discussed.

Case reportsPatient 1A 68-year-old man had hypertensive anterior uveitis of his left eye with a recurrence rate of one to two times a month since 2010. On slit-lamp examination at Seoul St. Marys Hospital in October 2012, fine KPs in the lower part of the cornea and mild inflammatory reaction in the

Table 4 Association between the presence CMV DNA in aqueous and corneal endothelial cell count in patients with anterior hypertensive uveitis

Model 1 Model 2 Model 3 Unadjusted Adjusted for

age and gender

Adjusted for age,

gender, lens status,

and history of

glaucoma surgery B (CI) B (CI) B (CI)

CMV positivity 672.4 734.4 1034.2(77.01267.9) (116.41352.4) (631.31437.1)

P value 0.029 0.023 <0.001

B beta coefficient, CI confidence interval

Choi et al. Journal of Ophthalmic Inflammation and Infection (2016) 6:32 Page 5 of 7

anterior chamber were seen. The corneal endothelial cell count of the left eye was 2141 cells/mm2, and the IOP was 22 mmHg with two topical antiglaucoma medications. He showed glaucomatous optic disc changes, with a mean deviation of 9.50 dB. Despite the use of topical steroids and three antiglaucoma medications for 5 months, his IOP was not controlled, and his corneal endothelial cell count in the left eye decreased to 1245 cells/mm2. A CMV-quantitative PCR analysis of aqueous humor samples for the left eye revealed 229,000 copies/mL CMVDNA, but no HSV-DNA. Thus, an oral course of valacyclovir (90 mg/day) was started. The ExPRESS glaucoma filtration device (P-200) was implanted under a scleral flap. Oral valacyclovir (900 mg/day) was continued for 10 days, and anterior chamber tapping revealed 66,600 copies/mL CMV-DNA. Oral valacyclovir treatment (450 mg/day) was continued for another 14 days, and repeated anterior chamber tapping revealed 630 copies/mL CMV-DNA. After glaucoma surgery, the anterior chamber had a rare to +1 grade inflammation, and IOP was well controlled in a range of 69 mmHg. However, 5 months later, his corneal endothelial cell count was found to have decreased further, to 981 cells/mm2 (Fig. 1).

Patient 2A 64-year-old man had hypertensive anterior uveitis of his left eye with a recurrence rate of one to two times a month since 1991. He had been diagnosed with Posner-Schlossman syndrome, but chronic inflammation in the anterior chamber with uncontrolled IOP elevation was seen, and he was referred to Seoul St. Marys Hospital for glaucoma surgery. At the initial visit, mutton-fat keratic precipitates were noted in the central cornea with minimal anterior chamber reaction (Fig. 2). IOP was 21 mmHg with three antiglaucoma medications, and high pigmentation was noted in the anterior chamber angle. Severe glaucomatous optic disc was seen, with

a mean deviation of 18.20 dB. The corneal endothelial cell count of the left eye was 1310 cells /mm2. A CMV-quantitative PCR analysis of an aqueous humor sample for the left eye revealed 44,609 copies/mL CMV-DNA, but no HSV-DNA. Oral valacyclovir treatment (900 mg/day) was started, and an Ahmed glaucoma valve was implanted. After 14 days of oral valacyclovir treatment, the aqueous humor showed 6980 copies/mL CMV-DNA. Oral valacyclovir was continued for 14 days, and further anterior chamber tapping showed 450 copies/mL CMV-DNA. After 1 month, the corneal endothelial cell count of the left eye was 1310 cells/mm2.

Discussions

We reported the clinical characteristics of hypertensive anterior uveitis (Table 1), which occurred unilaterally (93 %), predominantly in middle-aged (57.6 17.0 years) males (69.0 %; Table 1). Despite seemingly mild intraocular inflammation of the anterior chamber in the majority of patients (88.1 %) and the absence of peripheral anterior synechiae (0 %), glaucoma surgeries were required in over half of the patients (52.4 %). The male dominance in hypertensive anterior uveitis is consistent with previous results in non-Korean populations [4, 7]. Among the patients who underwent aqueous sampling, six (28.6 %) patients were positive for CMV-DNA. This prevalence is similar to the previous studies, reporting 22.8 % of anterior uveitis associated with raised IOP [1, 4].

Notably, the corneal endothelial cell count in the CMV-positive subjects was significantly lower than in the CMV-negative subjects (P = 0.009; Table 2). This association between the presence of CMV-DNA and the corneal endothelial cell count was more evident after adjusting for age, gender, lens status, and history of glaucoma surgery (P < 0.001; Table 3). Previous studies demonstrated that CMV is an important pathogen for chronic corneal endotheliitis, particularly in Asian

Fig. 1 Case 1: serial follow-up of specular microscopy. At the initial visit, the corneal endothelial count in the left eye was 2141 cells/mm2 (a). After topical steroid and three antiglaucoma medications for 5 months, the corneal endothelial cell count decreased to 1245 cells/mm2 (b). A CMV-quantitative

PCR analysis of aqueous humor samples revealed 229,000 copies/mL CMV-DNA. After valacyclovir treatment for 1 month, repeated anterior chamber

tapping revealed 630 copies/mL CMV-DNA. However, the corneal endothelial cell count had decreased further, to 981 cells/mm2 (c)

Choi et al. Journal of Ophthalmic Inflammation and Infection (2016) 6:32 Page 6 of 7

Fig. 2 Case 2: slit lamp photograph showing diffuse mutton-fat

keratic precipitates within the central area of the cornea. There was

mild inflammation in the anterior chamber

populations [79, 13]. This study confirmed that CMV is a major cause of corneal endothelial cell loss in patients with hypertensive anterior uveitis.

Evidence of valacyclovirs efficacy was seen in our study, using serial follow-up of CMV-DNA copy number and corneal endothelial cell counts in two case patients. After 1 month of therapy, CMV-DNA copy numbers decreased dramatically in both patients. Considering that patient 1 showed very high CMV-DNA copy numbers (44,609 copies/mL), it seems that one episode of acutely increased viral load is sufficient to cause extensive cor-neal endothelial cell loss. Consistent with our study, Kandori et al. [11] also reported a significant correlation between CMV viral load and corneal endothelial cell loss in CMV-associated uveitis.

We found that the proportion of monocytes tended to be lower in CMV-positive subjects, with marginal significance (P = 0.053; Table 2). Monocytes are the primary cell type of CMV persistence within the peripheral blood mononuclear cells [14]. CMV infection of monocytes induces trans-endothelial migration and monocyte to macrophage differentiation, which is productive for CMV replication [15]. Although the reason is unclear, CMV-induced differentiation of monocytes into macrophages may be associated with the lower proportion of monocytes in CMV-positive subjects in this study.

We found that the CMV-positive subjects were significantly younger (P = 0.006, Table 2). Generally, CMV seropositivity increases with age and serves as an immune risk phenotype, which is associated with survival in an older population [16, 17]. The current understanding of the mechanisms by which CMV reactivates in relatively young immunocompetent subjects is very limited. CMV is unlikely to cause clinically significant symptoms as long as it is maintained in balance by the

host immune system [18]. However, recent literature suggests that CMV is associated with the pathogenesis of cardiovascular diseases, such as atherosclerosis, auto-immune disease, and even certain cancers [19, 20]. It is known that CMV can be reactivated when circulating monocytes with latent CMV are recruited to sites of inflammation [20]. For this reactivation, inflammatory cytokines, such as tumor necrosis factor and interferon, are known to play a role [21, 22]. In this regard, it is suggested that chronic inflammation in the anterior chamber may trigger CMV reactivation, which in turn, aggravates the inflammatory condition. In addition, CMV anterior uveitis is recalcitrant to topical steroid treatment [3, 4]. Recent reports show evidence that local immunosuppression by topical steroid use increases the risk of CMV infection in immunocompetent patients [2326]. In addition, there is possibility that the frequent use of prostaglandin eyedrops have play an important role for worsening, including the uncontrolled glaucoma, considering previous reports regarding the complications from glaucoma eyedrops in uveitis [2729].

Conclusions

In conclusion, we found that CMV was a significant etiological factor in hypertensive anterior uveitis patients in Korea. In CMV-associated uveitis, extensive corneal endothelial cell damage may occur, even with effective anti-viral medication. CMV-associated hypertensive anterior uveitis patients were younger compared to CMV-negative uveitis patients. Special caution is needed for patients with CMV-positive hypertensive anterior uveitis, given its adverse effects on the corneal endothelium.

Additional file

http://dx.doi.org/10.1186/s12348-016-0100-5

Web End =Additional file 1: Table S1. Demographic data and clinical manifestations of patients with the presence of cytomegalovirus in the aqueous. (DOCX 15 kb)

Acknowledgements Not applicable.

FundingThe authors wish to acknowledge of the financial support of the National Research Foundation of Korea Grant funded by the Korean government (MSIP) (No. NRF- 2016R1C1B1011287).

Authors contributionsJAC and CKP contributed to the conception and design. JAC, KSK, and YHJ contributed to the acquisition of data and analysis and interpretation of data. JAC contributed in drafting the manuscript. HYLP contributed in revising the manuscript. CKP gave the final approval of the version to be published. All authors read and approved the final manuscript.

Competing interestsThe authors declare that they have no competing interests.

Choi et al. Journal of Ophthalmic Inflammation and Infection (2016) 6:32 Page 7 of 7

Ethics approvalThe study protocol was approved by the institutional review/ethics boards of Seoul St. Marys Hospital, the Catholic University of Korea (IRB number: KC14RISI0513).

Author details

1Department of Ophthalmology and Visual Science, St. Vincents Hospital, College of Medicine, The Catholic University of Korea, 93-6, Ji-dong, Paldal-gu, Suwon, Kyonggi-do 442-060, Republic of Korea. 2Department of Ophthalmology and Visual Science, Seoul St. Marys Hospital, College of Medicine, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul 137-701, Republic of Korea.

Received: 11 April 2016 Accepted: 22 August 2016

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