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CLINICAL SCIENCES

Clinical Manifestations of Cytomegalovirus-AssociatedPosterior Uveitis and Panuveitis in Patients WithoutHuman Immunodeficiency Virus InfectionKessara Pathanapitoon, MD, PhD; Nattaporn Tesavibul, MD; Pitipol Choopong, MD; Sutasinee Boonsopon, MD;Natedao Kongyai, PhD; Somsanguan Ausayakhun, MD; Paradee Kunavisarut, MD; Aniki Rothova, MD, PhD

Importance: Little attention has been paid to clinicalfeatures of cytomegalovirus (CMV) infections in indi-viduals without human immunodeficiency virus (HIV).

Objective: To describe the clinical manifestations andcomorbidities of patients without HIV infection who haveCMV-associated posterior uveitis or panuveitis.

Design and Setting: Retrospective observational caseseries in an academic research setting.

Participants: The medical records were reviewed of 18patients (22 affected eyes) diagnosed as having poste-rior uveitis or panuveitis who had aqueous positive forCMV by polymerase chain reaction techniques.

Main Outcome Measures: Demographic data, clini-cal manifestations, and associated systemic diseases wererecorded.

Results: Ocular features included focal hemorrhagic reti-nitis (n=13) and peripheral retinal necrosis (n=7). Twoeyes had no focal retinal lesions but manifested vasculi-tis and vitritis. All patients exhibited vitreous inflamma-tion. Inflammatory reactions in anterior segments devel-oped in 14 of 22 eyes (64%). Retinal vasculitis wasobserved in 16 of 22 eyes (73%) and included mostly ar-

teries (in 13 of 16 eyes [81%]). Eleven of 18 patients weretaking immunosuppressive medications (5 for hemato-logic malignant diseases, 4 for systemic autoimmune dis-eases, and 2 following organ transplants). One addi-tional patient was diagnosed as having non-Hodgkinlymphoma 3 months after the onset of CMV-associatedpanuveitis, and another patient had primary immuno-deficiency disorder. Of the remaining 5 patients, 2 haddiabetes mellitus, and 3 had no associated systemic dis-eases and exhibited no evidence of immune deficiency.

Conclusions and Relevance: Cytomegalovirus-associated infections of posterior eye segments can de-velop in patients without HIV infection who have com-promised immune function of variable severity but mayoccur also in individuals who have no evidence of im-mune insufficiency. Cytomegalovirus infections lo-cated in posterior eye segments in patients without HIVinfection caused intraocular inflammatory reaction in allcases and demonstrated more variable clinical presenta-tion than classic CMV retinitis observed in patients withHIV infection.

JAMA Ophthalmol. 2013;131(5):638-645.Published online March 14, 2013.doi:10.1001/jamaophthalmol.2013.2860

C YTOMEGALOVIRUS(CMV)IS

a common cause of poste-rioruveitis inpatientswithsevere immunosuppres-sion. The main cause of

blindness in patients who have human im-munodeficiency virus (HIV) infection isCMV retinitis, with prevalences of approxi-mately 30% before the era of highly activeantiretroviral therapy (HAART) and 22%in the HAART era.1,2 Cytomegalovirus reti-nitis occurs predominantly during the endstage of disease in patients with severely de-creased CD4 cell counts.3 In addition, CMVretinitis has been reported in patients with-out HIV infection who are taking aggres-sive immunosuppressive medications and

has been sporadically diagnosed in pa-tients who are receiving immunosuppres-sive treatments for malignancy and auto-immune diseases.4-11 Recently, several casesof CMV retinitis have been reported afterintraocular administration of triamcino-lone acetonide.12-14 In contrast, few cases ofCMV retinitis have been diagnosed amongimmunocompetent patients.15-18

Little attention has been paid to clini-cal features of CMV infection in individu-als without HIV infection, although a com-prehensive literature review shows thatsevere clinical manifestations of CMV in-fection in immunocompetent patientsmight not be so uncommon as originallythought.16 In this article, we describe 18

Author AffDepartmenFaculty of MPathanapitoand KunaviDepartmenTechnologyAssociatedKongyai), CUniversity,DepartmenFaculty of MHospital, MBangkok (DChoopong,Thailand; aOphthalmoMedical CeDepartmenErasmus MRotterdam,Rothova).

Author Affiliations are listed atthe end of this article.

JAMA OPHTHALMOL/ VOL 131 (NO. 5), MAY 2013 WWW.JAMAOPHTH.COM638

©2013 American Medical Association. All rights reserved.

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patients without HIV infection who had uveitis locatedin the posterior eye segment and report on their clinicalmanifestations and immune status.

METHODS

We performed a retrospective review of the medical records of18 patients without HIV infection who had posterior uveitisor panuveitis and positive polymerase chain reaction (PCR) re-sults of intraocular fluids for CMV from 2 university hospitals(Chiang Mai University Hospital, Chiang Mai [n=13] and Siri-raj Hospital, Bangkok [n=5]) in Thailand.

Among 170 patients without HIV infection who had uve-itis with intraocular fluid analysis, these 18 patients repre-sented all patients from both hospitals without HIV infectionwho had posterior uveitis or panuveitis and had positive testresults for CMV in intraocular fluids (aqueous humor samplesin all patients) between January 2006 and December 2011. Pa-tients with HIV infection and patients with anterior uveitis onlywere excluded from the study.

Samples of intraocular fluid were obtained in patients withuveitis, as well as results of diagnostic screening, which in-cluded serologic testing for Treponema pallidum and Toxo-plasma gondii and a chest radiograph. When appropriate, a tu-berculin skin test was also administered. Polymerase chainreaction of intraocular fluids for CMV and for human herpes-virus types 1, 2, and 3 was performed on all samples as de-scribed previously (herpesvirus type 3 is also known as varicella-zoster virus).19 Nucleic acid was extracted from 25 �L ofintraocular fluid using a commercially available kit (QIAampDNA Blood Mini Kit; QIAGEN, Inc). Before extraction, 2500to 5000 copies/mL of phocid herpesvirus type 1 were added toeach sample to monitor the quality of extraction and the am-plification procedures.20 Each focal pathogenic DNA was sepa-rately analyzed by real-time PCR with a repeated cycling pro-gram as previously described.21 Briefly, 10 �L of the extractednucleic acid was added to 15 �L of the real-time PCR reactionmixture kit (DyNAmo Probe qPCR; New England Biolabs, Inc),which contained specific primers and probes. Then, real-timePCR was performed in a detector machine (Chromo4 DNA En-gine; Bio-Rad). The lowest detection limits were 3.4�104 cop-ies/mL for CMV infection, 4.8�104 copies/mL for human her-pesvirus types 1 and 2 infection, 5.5�104 copies/mL for humanherpesvirus type 3 infection, and 4.6�104 copies/mL for T gon-dii infection. Included in the study were patients with a posi-tive PCR result for CMV only and negative results for other testedpathogens.

Each patient underwent a full ophthalmic examination, in-cluding slitlamp biomicroscopy, tonometry, and indirect oph-thalmoscopy. Uveitis was classified according to the anatomi-cal localization as determined by the Standardization of UveitisNomenclature (SUN) Working Group.22 We recorded the demo-graphic data of the patients, their associated systemic dis-eases, concurrent medication use, and ocular manifestations.This study was performed with the approval of local medicalethics committees. The Fisher exact t test was used for statis-tical analyses. P� .05 was considered statistically significant.

RESULTS

Our study included 18 patients (22 eyes), with a meanage of 49 years (age range, 29-65 years). There were 11male patients and 7 female patients (6 with posterior uve-itis and 12 with panuveitis). Unilateral involvement waspresent in 14 patients, and 4 had bilateral involvement,

resulting in 22 affected eyes. The mean follow-up timewas 24 months (range, 3-60 months).

Eleven of 18 patients were taking immunosuppres-sive medications; specifically, 2 of the patients had re-ceived organ transplants, 4 of the patients had autoim-mune connective tissue diseases, and 5 of the patientshad hematologic malignant diseases (4 non-Hodgkin lym-phoma and 1 acute myeloid leukemia). One additionalpatient had primary immunodeficiency disorder, and an-other patient was diagnosed as having non-Hodgkin lym-phoma 3 months after the onset of CMV-associated panu-veitis (including features of corneal endotheliitis, elevatedintraocular pressure, and retinal necrotic lesions)(Figure 1A and B, and Table 1). Of the remaining 5patients, 2 had diabetes mellitus (DM), associated withnonproliferative diabetic retinopathy in both cases, andthe other 3 had no systemic diseases or use of medica-tions that could alter their immune system. During thefollow-up period, no signs or symptoms of systemic dis-ease or alterations of the immune system were noted (2patients completed follow-up periods of 2 years, and 1patient completed a follow-up period of 4 years after theonset of CMV eye infection) (Table 1).

The CD4 cell counts were available in 4 patients (3 withnon-Hodgkin lymphoma and 1 with congenital immuno-deficiency). The results ranged from 181 to 427 cells/�L.

Clinical features of 22 eyes are given in Table 2 andTable 3. In total, 13 of 22 eyes (59%) had focal hem-orrhagic retinal lesions (Figure 1C); 7 of 22 eyes (32%)exhibited peripheral retinal necrosis (3 with hemorrhag-ing and 4 without hemorrhaging) (Figure 1D and E). Tworemaining eyes (9%) had no focal retinal lesions, and bothwere initially seen with vitritis and retinal vasculitis only(Figure 2A). Areas with indolent granular retinitis werepresent in 2 eyes (one in combination with retinal ne-crosis and the other in combination with a focal retinallesion) (Figure 2B and C).

Retinal vasculitis was present in 16 of 22 eyes (73%),and 13 of 16 (81%) involved the arteries only. Three re-maining eyes exhibited (in addition to their retinal le-sions) frosted branch angiitis, which predominantly in-volved veins (Figure 2D and E).

Vitritis was present in 22 of 22 (100%) affected eyes.Anterior segment inflammation was noted in 14 of 22 eyes(64%). One of our patients initially had anterior uveitiswith endotheliitis and posterior involvement typical ofCMV retinitis (Figure 1A and B).

The clinical manifestations did not differ among thevarious subgroups of our patients (Table 3) but few pa-tients were included in the subgroups. All 5 patients with-out evident immunosuppression showed unilateral in-volvement; 1 had a focal retinal lesion, 2 demonstratedperipheral retinal necrosis, and 2 exhibited only vitritisand vasculitis, without other retinal lesions. All 5 mani-fested severe vitritis, and all had retinal arteritis; ante-rior chamber inflammatory reactions were present in 4of 5 eyes. One patient with DM had features of acute reti-nal necrosis (ARN), and the other patient with DM hada focal necrotic lesion. Three patients who were not tak-ing immunosuppressive medications and who had no DMor other causes or disorders associated with possible im-munosuppression were aged 26, 29, and 41 years at the




onset of their uveitis. Two patients had retinal vasculitisand vitritis and subsequently developed epiretinal mem-branes with traction.

In general, treatment with systemic (n = 5) and intra-ocular (n = 11) ganciclovir sodium had a beneficial ef-fect on inflammatory signs, and the ocular lesions be-came inactive within 6 to 8 weeks. Immunosuppressivemedications were decreased or withdrawn in 4 of 11 pa-tients, none of whom exhibited features consistent withimmune reconstitution uveitis (increase in inflamma-tion and development of macular edema). During the fol-low-up period, retinal detachment developed only in 1eye of a patient with non-Hodgkin lymphoma and ocu-

lar features of ARN, which had an incidence of 3% perperson per eye-year (1 case in 30.4 person eye-years). Parsplana vitrectomy was performed in patients with epireti-nal membranes and traction (2 eyes) or retinal detach-ment (1 eye).

COMMENT

Our results document that posterior uveitis and panu-veitis due to CMV can develop in patients without HIVinfection who have moderate or slight degrees of immu-nosuppression, as well as in occasional patients without

A

B

D

E

C

Figure 1. Clinical presentation of cytomegalovirus-associated posterior uveitis and panuveitis in patients 4, 10, and 13 in Table 1. A and B, Cytomegalovirus-associatedpanuveitis in a 49-year-old woman (patient 4) who was seen with decreased vision in the left eye for 3 months. During the screening for uveitis, B-cell non-Hodgkinlymphoma was diagnosed. The anterior segment exhibited stellate keratic precipitates and endotheliitis; necrotic retinitis with hemorrhaging and vitritis were alsoobserved. C, Cytomegalovirus-associated focal hemorrhagic retinitis in a 59-year-old man (patient 13) who had been receiving cyclophosphamide therapy for nephritisdeveloped cytomegalovirus-associated unilateral posterior retinitis and vitritis. D and E, Cytomegalovirus-associated peripheral retinal necrosis and arteritis in a54-year-old man (patient in 10) who had been receiving tacrolimus therapy after undergoing renal transplantation 3 years previously.




any evidence of immunosuppression, during several fol-low-up years. Furthermore, we showed that all patientswithout HIV infection who had posterior segment in-volvement due to CMV exhibited associated inflamma-tion in the vitreous and that 14 of 22 affected eyes (64%)developed an inflammatory reaction in the anterior cham-ber (Table 1). The presence of retinal vasculitis was a com-mon characteristic (occurring in 16 of 22 eyes [73%]),predominantly involving arteries. The retinal features re-sembled in part the typical manifestations of CMV reti-nitis found in patients with HIV infection, described ashemorrhagic and granular types of retinitis, but our casesalso included manifestations typical of ARN, as well ascases with retinal vasculitis associated with vitritis.

Cytomegalovirus is a ubiquitous member of the fam-ily of human herpesvirus types 1 and 2, and the sero-prevalence of CMV is about 90% among the Thai adultpopulation.23 Cytomegalovirus retinitis can occur in pa-tients who have deficient T-cell responses against the CMV(usually due to the HIV infection or to the immunosup-pressive medication), and the prevalence of CMV reti-nitis has been linked to the degree of immunosuppres-sion.24 Systemic CMV infection in patients with a healthyimmune system has often been reported to be subclini-cal, while ocular involvement during viremia has not been

regularly documented. However, a 2008 review of se-vere systemic CMV infection among 290 immunocom-petent adults demonstrated that the most frequent sites

Table 2. Clinical Manifestations of 18 Patients WithoutHuman Immunodeficiency Virus Who Had Posterior Uveitisor Panuveitis Due to Cytomegalovirus Infection

Clinical Feature

Affected Eyes,No. (%)(N = 22)

Fine keratic precipitates 8 (36)Endotheliitis 1 (5)Anterior chamber cells 14 (64)Posterior synechiae 2 (9)Focal hemorrhagic retinitis 13 (59)Granular retinitis 2 (9)Acute retinal necrosis 7 (32)No focal retinal lesions, only vasculitis

and vitritis2 (9)

Retinal arteritis 13 (59)Frosted branch angiitisa 3 (14)Vitritis 22 (100)Intraocular pressure �24 mm Hg 3 (14)

aOne eye in combination with focal retinitis and another eye incombination with retinal peripheral necrosis.

Table 1. Immunosuppressive Medication Use and Comorbidity in Patients With Cytomegalovirus (CMV)–AssociatedPosterior Uveitis or Panuveitis

Patient No./Sex/Age, y

ImmunosuppressiveMedication Use at the Onsetof CMV-Associated Uveitis Comorbidity Remarks

1/M/42 None Primary immunodeficiency disorder . . .2/M/64 None Diabetes mellitus Glycated hemoglobin, 10.0%3/F/50 None Diabetes mellitus Glycated hemoglobin, 8.9%4/F/49 None Diagnosis of non-Hodgkin lymphoma 3 mo

after onset of CMV-associated uveitis. . .

5/M/50 None Non-Hodgkin lymphoma Completed 2 cycles of chemotherapy 2 mobefore the onset of CMV-associated uveitisa



8/F/59 None Non-Hodgkin lymphoma Completed 8 cycles of chemotherapy 9 mobefore the onset of CMV-associated uveitisa

9/F/52 None Acute myeloid leukemia Completed 8 cycles of chemotherapy 5 mobefore the onset of CMV-associated uveitisb

10/M/54 Tracrolimus (6 mg/d) Renal transplant . . .11/F/58 Cyclosporine (150 mg/d) Renal transplant . . .12/F/45 Prednisolone (40 mg/d),

azathioprine (100 mg/d)Myasthenia gravis and transverse myelitis Died 1 mo after the onset of CMV-associated

uveitis13/M/59 Prednisolone (10 mg/d),

cyclophosphamide (50 mg/d)Nephritis . . .

14/F/39 Prednisolone (10 mg/d),cyclophosphamide (25 mg/d)

Systemic lupus erythematosus . . .

15/M/45 Prednisolone (40 mg/d) Idiopathic thrombocytopenic purpura . . .16/M/29 None None No evidence of disorder associated with immune

deficiency during a 2-y follow-up period17/M/26 None None No evidence of disorder associated with immune

deficiency during a 2-y follow-up period18/M/41 None None No evidence of disorder associated with immune

deficiency during a 2-y follow-up period

Abbreviation: Ellipsis, not applicable.aNon-Hodgkin lymphoma chemotherapy included a combination of rituximab, vincristine sulfate, cyclophosphamide, and prednisolone.bAcute myeloid leukemia chemotherapy included a combination of fludarabine phosphate, idarubicin hydrochloride, and cytosine arabinoside.




of severe CMV infection in these patients were the gas-trointestinal tract and the central nervous systems; eyeinvolvement was also noted.25 That series included 16 pa-tients with all types of eye involvement, including con-junctivitis and anterior and posterior eye segmentinflammation.

The largest study of patients without HIV infectionwho had CMV retinitis, published by Kuo et al6 in 2004,included 18 patients with profound immunosuppres-sion diagnosed as having CMV retinitis on clinical groundsonly. In that study, the rates of mortality, vision loss, andimmune reconstitution uveitis were found to be similarto those of patients with HIV infection and CMV retini-tis receiving HAART. Immune reconstitution uveitis oc-curred in 4 of 18 patients (incidence of 13% per person-year); however, the number of patients in whomimmunosuppressive treatment could be decreased or with-drawn was not given. These results contrast with thoseof our series, which included patients with less severeor the absence of immunosuppression. In our study, im-munosuppressive treatment was decreased or with-drawn in 4 of 11 patients, but none developed featuresof immune reconstitution uveitis during the follow-upperiod. Intraocular inflammation was present in all of ourpatients with CMV, in contrast to the series by Kuo etal.6 Moreover, the mortality in their study was high (23%per person-year vs 3% per person-year in our series). Thesediscrepancies can be explained by different inclusion cri-teria and by more severe immunosuppression among pa-tients in the earlier study. The incidence rate of retinaldetachment found previously among patients without HIVinfection who had CMV retinitis was similar to our re-sults (3.7% vs 3% per eye-year), which is lower than theincidence rates among patients who have HIV and CMVretinitis (22% with HAART and 44% without HAART).6,26

Ocular manifestations of CMV infection in hosts withHIV infection have been extensively reported.2,26-31 How-ever, systematic studies5,6 on the clinical manifestations

of CMV infection in posterior eye segments among pa-tients without HIV infection are rare.

The clinical manifestations of HIV-associated CMV reti-nitis include the classic features of necrotizing retinitis,with variable degrees of hemorrhaging (“cottage cheesewith ketchup” or “pizza pie” retinopathy), as well as agranular form of retinitis that is sometimes in combina-tion with frosted branch angiitis; associated inflamma-tory signs are lacking.27-31 In contrast to clear media ob-served by Kuo et al,6 all of our patients demonstratedassociated vitritis, and more than half had concurrent an-terior uveitis, while the absence of intraocular inflam-mation in patients with HIV infection and CMV retinitisis typical.27-31 Our findings clearly show that the charac-teristics of posterior segment involvement caused by CMVin patients without HIV infection represent a much widerspectrum of clinical manifestations, which include fre-quent prevalence of retinal arteritis, variable signs of in-traocular inflammation, and the presence of retinal in-volvement, varying from focal lesions to extended ARN.Seven of our patients without HIV infection who had CMVexhibited clinical characteristics of ARN. The preva-lence of the clinical syndrome of ARN among individu-als with HIV infection varies between 0.4% and 1.1%,2,32

which is much lower than that in our series. Acute reti-nal necrosis is mostly associated with human herpesvi-rus types 1, 2, and 3, but occasional CMV cases have beenreported.33 The presence of ARN due to CMV has beenreported in a patient without HIV infection who had DM.34

The retinal vessels may have an important role in thepathogenesis of CMV retinitis. Clinically, the areas of CMVretinitis are located along the retinal vessels, and immu-nohistochemical studies35,36 have revealed the presenceof CMV proteins in the retinal vascular endothelium inthe areas adjacent to retinal necrosis. It has been pro-posed that CMV infection in the retina initially occursin the vascular endothelium. The association of HIV vas-culopathy and subsequent retinitis has been reported.37

Table 3. Clinical Manifestations of Cytomegalovirus (CMV)–Associated Posterior Uveitis or Panuveitis in PatientsWith vs Without Immunosuppression

Variable

Eyes in PatientsWith Immunosuppression

(n = 17)

Eyes in PatientsWithout Immunosuppression

(n = 5)

P Value

OrganTransplantation

(n = 3)

HematologicMalignancy

(n = 7)

AutoimmuneDisease(n = 5)

PrimaryImmunodeficiency

Disorder(n = 2)

No AbnormalityExcept Ocular

Disease(n = 3)

DiabetesMellitus(n = 2)

Clinical Feature, No. (%)Focal retinal lesions 2 (67) 4 (57) 4 (80) 2 (100) 1 (33) 0 .06Peripheral retinal necrosis 1 (33) 1 (14) 3 (60) 0 0 2 (100) .52Retinal vasculitis 3 (100) 4 (57) 3 (60) 1 (50) 3 (100) 2 (100) .32Retinal hemorrhaging 3 (100) 2 (29) 5 (100) 0 2 (67) 1 (50) .29Anterior uveitis 1 (33) 5 (71) 2 (40) 2 (100) 2 (67) 2 (100) .38Vitritis 3 (100) 7 (100) 5 (100) 2 (100) 3 (100) 2 (100) Not availableIntraocular pressure �24 mm Hg 0 1 (14) 0 0 1 (33) 1 (50) .11Visual acuity at the onset

of CMV-associated uveitis �0.11 (33) 2 (29) 3 (60) 0 2 (67) 0 .62

Ratio of Unilateral to Bilateral InvolvementUnilateral-bilateral involvement 1:1 5:1 3:1 0:1 3:0 2:0 .07




In our series, a high prevalence of vascular involvementamong patients without HIV infection who had CMV in-fection was noted, and 2 patients without necrotic reti-nal changes manifested severe vasculitis only. Involve-ment of retinal vessels is common in CMV retinitis andcan affect arteries and veins. The exact role of HIV vas-culopathy in the development of CMV retinitis amongpatients with HIV infection is controversial.35,38 Predomi-nant involvement of retinal veins among individuals withHIV infection and CMV retinitis has been noted and con-sisted primarily of perivenous sheathing.39,40 In con-trast, we observed primary involvement of retinal arter-

ies in our patients without HIV infection who had CMVand posterior uveitis. The predominance of retinal arte-ritis was also noted in ARN associated with human her-pesvirus types 1, 2, or 3 infection.41 It may be that reti-nal necrosis due to viral infections (including CMV) inpatients without HIV infection is frequently associatedwith involvement of retinal arteries. The severe loss ofimmunity in patients with HIV infection might explainthe absence of arteritis even in the presence of retinal ne-crotic lesions. A severe retinal vasculitis, frosted branchangiitis may be associated with multiple infective agents,including CMV.27-31 Frosted branch angiitis was ob-

A

B

D

E

C

Figure 2. Clinical presentation of cytomegalovirus-associated posterior uveitis and panuveitis in patients 5, 8, and 18 in Table 1. A, A 41-year-old healthy man(patient 18) without evidence of previous immunosuppression was seen with severe unilateral vitritis complicated by epiretinal membrane formation and retinaltraction. After pars plana vitrectomy, severe vasculitis and sheathing became visible, but retinal lesions were not observed. B and C, A 59-year-old woman (patient8) with non-Hodgkin lymphoma had been successfully treated with chemotherapy. She developed cytomegalovirus-associated unilateral peripheral retinalnecrosis, areas of granular retinitis, and retinal arteritis 16 months after the diagnosis of non-Hodgkin lymphoma. D and E, A 50-year-old man (patient 5) withunderlying non-Hodgkin lymphoma had been receiving repeated cycles of chemotherapy. He developed cytomegalovirus-associated panuveitis with focal retinitisand peripheral retinal necrosis, as well as frosted branch angiitis.




served in our series in 3 of 22 eyes (14%) and was al-ways associated with the presence of retinitis.

In our series, 2 of 5 patients (both with nonprolifera-tive diabetic retinopathy) who were not receiving immu-nosuppressive medications had DM. Notably, 2 patientswithout HIV infection who had DM have been previouslyreported as having PCR-proved CMV-associated panuve-itis and exhibited multiple keratic precipitates, vitreousopacities, necrotic retinal lesions, and arterial sheathing.42

Some research has suggested that CMV infection might beassociated with DM and its complications.43,44 In vitro stud-ies45,46 of the immune cells of patients with DM have dem-onstrated significant defects that bear similarity to abnor-malities described in immunodeficiency syndromes and thatwere hypothetically related to the frequent and chronic de-velopment of infections among individuals with DM. How-ever, it might also be feasible that vasculopathy present inDM may have an important role in the development of CMVinfection among individuals with DM.

The CMV-induced focal retinitis in our series was fre-quently associated with hemorrhaging, and no eyesshowed associated pigmented scars, which might helpto differentiate these lesions from ocular toxoplasmosis.Two of our patients without evident immune system ab-normalities had no necrotic retinal lesions and were ini-tially seen with vitritis and vasculitis only (manifestingin both arteries and veins), which indicates the possibil-ity of CMV involvement in the pathogenesis of retinalvasculitis in immunocompetent patients.

Cytomegalovirus-associated anterior uveitis repre-sents a distinct clinical entity that occurs in immuno-competent patients and has been reported mainly in Asia,47

but sporadic cases from Europe have also been de-scribed.48 The exact pathogenesis of CMV-associated an-terior uveitis and its association with primary systemicinfection remain unknown.49 Some of the typical mani-festations of this entity, such as endotheliitis and highintraocular pressure,47,48 were also observed in the ante-rior segments of our patients.

The retrospective nature of our study precludes anyconclusions about the prevalence of CMV infection inposterior eye segment inflammation. The limited num-ber of patients included in our study prevents a full de-piction of clinical signs associated with CMV infectionin patients without HIV infection.

In conclusion, CMV-associated infection of poste-rior eye segments can develop in patients without HIVinfection who have variable degrees of compromised im-mune function but may also occur in individuals whohave no evidence of immune insufficiency. Clinical fea-tures of CMV-associated posterior segment eye infec-tion in patients without HIV infection might differ fromthose of patients with HIV infection and typically in-clude signs of intraocular inflammation and the pres-ence of vasculitis, with the frequent involvement of ar-teries. Retinal necrotic lesions are often (but not always)present, and 7 of our patients without HIV infection whohad CMV infection in posterior eye segments exhibitedtypical features of ARN. It may be that CMV infectionlocated in posterior eye segments of patients without HIVinfection is more frequent and has more variable clini-cal presentation than previously thought.

Submitted for Publication: September 10, 2012; final re-vision received December 2, 2012; accepted December4, 2012.Published Online: March 14, 2013. doi:10.1001/jamaophthalmol.2013.2860Author Affiliations: Department of Ophthalmology, Fac-ulty of Medicine (Drs Pathanapitoon, Ausayakhun, andKunavisarut), and Department of Medical Technology,Faculty of Associated Medical Sciences (Dr Kongyai),Chiang Mai University, Chiang Mai, and Department ofOphthalmology, Faculty of Medicine, Siriraj Hospital, Ma-hidol University, Bangkok (Drs Tesavibul, Choopong, andBoonsopon), Thailand; and Department of Ophthalmol-ogy, University Medical Center, Utrecht, and Depart-ment of Ophthalmology, Erasmus Medical Center, Rot-terdam, the Netherlands (Dr Rothova).Correspondence: Kessara Pathanapitoon, MD, PhD, De-partment of Ophthalmology, Faculty of Medicine, ChiangMai University, 110 Intawaroros Rd, Chiang Mai 50200,Thailand ([email protected]).Author Contributions: Dr Pathanapitoon had full accessto all the data in the study and takes responsibility for theintegrity of the data and the accuracy of the data analysis.Conflict of Interest Disclosures: None reported.

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