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Year : 2020  |  Volume : 8  |  Issue : 3  |  Page : 109-111

Immune recovery uveitis associated with active cytomegalovirus retinitis: A rare presentation

Department of Ophthalmology, Sri Sankaradeva Nethralaya, Guwahati, Assam, India

Date of Submission24-Aug-2019
Date of Decision20-Oct-2020
Date of Acceptance21-Oct-2020
Date of Web Publication4-Dec-2020

Correspondence Address:
Mandabi Sengupta
Sri Sankaradeva Nethralaya, Guwahati - 781 028, Assam
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcor.jcor_72_19

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Immune recovery uveitis (IRU) is the ocular manifestation of immune reconstitution inflammatory syndrome in human immunodeficiency virus (HIV)-infected patients with cytomegalovirus (CMV) retinitis receiving highly active antiretroviral therapy (HAART). Here, we report the case of a 48-year-old HIV-infected patient, with poor adherence to HAART, who presented with gradual diminution of vision and pain in the left eye for 2 months. HAART was restarted along with anti-tubercular treatment for central nervous system tuberculosis 6 months ago. Clinical examination revealed the features of uveitis and active CMV retinitis. Laboratory investigations showed increased CD4+ T-lymphocyte count. We diagnosed the case as IRU associated with active CMV retinitis. The patient recovered with topical steroid and oral anti-CMV therapy. Although IRU is commonly seen in patients with inactive CMV retinitis, rarely this may be seen in association with active CMV retinitis, particularly when HAART therapy is initiated without treating CMV retinitis.

Keywords: Cytomegalovirus retinitis, highly active antiretroviral therapy, immune reconstitution inflammatory syndrome, immune recovery uveitis

How to cite this article:
Sengupta M, Das D, Paul S, Misra P, Chaudhary P, Shinde K. Immune recovery uveitis associated with active cytomegalovirus retinitis: A rare presentation. J Clin Ophthalmol Res 2020;8:109-11

How to cite this URL:
Sengupta M, Das D, Paul S, Misra P, Chaudhary P, Shinde K. Immune recovery uveitis associated with active cytomegalovirus retinitis: A rare presentation. J Clin Ophthalmol Res [serial online] 2020 [cited 2022 Jun 26];8:109-11. Available from: https://www.jcor.in/text.asp?2020/8/3/109/302201

  Introduction Top

Cytomegalovirus (CMV) retinitis is a common opportunistic infection in patients with human immunodeficiency virus (HIV). It may manifest as a progressive necrotizing retinitis, with little or no ocular inflammation.[1] Due to the advent of highly active antiretroviral therapy (HAART) regimen, many patient experiences immune reconstitution inflammatory syndrome (IRIS). IRIS, also known as immune reconstitution syndrome, is characterized by exaggeration of the treated opportunistic infection or unmasking of previously subclinical infection in patients with HIV after initiation of antiretroviral therapy.[2] Ocular manifestations of IRIS are referred to as immune recovery uveitis (IRU). The current definition of IRU (or IRIS) includes at least five main criteria: (1) being a patient with Acquired Immunodeficiency Syndrome (AIDS), (2) receiving HAART, (3) achieving an immune reconstitution indicated by increased CD4+ T-cell count over 100 cells/mm3 for at least 2 months, (4) having preexisting CMV retinitis which is currently in the inactive state, and (5) developing an intraocular inflammation that cannot be explained by drug toxicity or a new opportunistic infection.[2] IRU is most commonly associated with inactive CMV retinitis.

We, herein, present the case of a 48-year-old male, infected with HIV and is on HAART therapy, who presented to us with IRU in the presence of active CMV retinitis.

  Case Report Top

A 48-year-old male patient presented to us with chief complaints of progressive blurring of vision and pain in the left eye for 2 months. He had been diagnosed with HIV-1 infection 9 years back and HAART therapy was started. However, he discontinued medications on his own for past 3 years. Six months ago, he developed central nervous system (CNS) tuberculosis, and he was being treated elsewhere with anti-tubercular treatment (ATT) and HAART regimen was re-started. On examination, his best-corrected visual acuity was 6/6 in the right eye and hand movement positive (HM+) in the left eye. On slit-lamp examination of the left eye, there was circum-ciliary congestion; keratic precipitates were present on corneal endothelium. Anterior chamber cells were 2+ (SUN Working Group Grading),[3] and also, flare was present. Intraocular pressure was 15 mm of Hg in both eyes. On the posterior segment examination, there was vitreous haze. Fundus examination showed whitish areas of retinal necrosis associated with retinal hemorrhages involving almost the entire posterior pole and extending up to zone 2 and 3 [Figure 1]. Right eye fundus was within normal limit.
Figure 1: Color montage fundus photo of the left eye showing whitish areas of retinal necrosis with retinal hemorrhages involving Zone 1, 2, and 3

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According to the patient, he was on lamivudine, abacavir, and efavirenz along with ATT (isoniazid and rifampicin). Laboratory investigations revealed, CD3+/CD45+ 73%, CD3+ absolute count 1766 cells/mL, T-helper % of lymphocyte (CD3+ CD4+/CD45+) 26% and T-helper lymphocytes (CD4+) absolute count was 324 cells/mL. Based on the laboratory result, which shows an increased CD4 count and the patient being on HAART therapy, he was diagnosed with a case of IRU associated with CMV retinitis. He was prescribed topical prednisolone acetate, 1 drop four times daily in the left eye for 2 weeks and oral gancyclovir, 1000 mg thrice daily for 6 weeks and advised to continue HAART and ATT. On next follow-up after 1 week, he showed the signs of improvement. He completed the course of ATT in the next 2 months, and by that time, the topical steroid was also gradually tapered off. He was advised to continue with maintenance dose of oral gancyclovir along with HAART regimen. On subsequent follow-up visit after 6 months, the patient showed resolution of inflammation and CMV retinitis with an improvement in visual acuity up to 6/36 in the left eye.

  Discussion Top

CMV retinitis occurs in severely immune-compromised HIV-infected patients, with CD4+ T-lymphocyte counts of <50 cells/mm3. Before HAART era, CMV retinitis occurred in at least 30% of people with AIDS.[4] With the advent of HAART therapy, the incidence of CMV retinitis has declined by 75%–90% approximately.[1] However, it still remains a leading cause of ocular morbidity in HIV patients.[5]

IRU is a noninfectious ocular inflammation that develops in patients with CMV retinitis (or infrequently with other intraocular infections, such as tuberculosis or toxoplasmosis) showing substantial increase in the number of CD4+ T-lymphocyte several weeks after initiation of HAART. It may even develop months to years after an immune recovery with HAART. Ortega-Larrocea et al.[6] noted that early introduction of HAART in patient with CMV retinitis before completing induction therapy for CMV results in a higher incidence of IRU (71%) than among those who had suppressed CMV retinitis before starting HAART (31%). This suggests that in such patient anti-CMV induction therapy should be started first followed by HAART therapy. Visual loss in patients with IRU is mostly due to macular pathology, cystoid macular edema and epiretinal membrane. A large cohort study evaluated the prevalence and risk factors for IRU and out of the 50 patients with CMV and IRU, none showed the signs of active retinitis.[7]

The peculiarity of our case is the co-existence of IRU and active CMV retinitis in the patient 6 months after initiation of HAART. The patient also had an episode of CNS tuberculosis diagnosed 6 months back, when ATT and HAART therapy was initiated. Although the CD4+ T-lymphocyte count during that period is not available, it can be assumed that initiation of HAART therapy without any anti-CMV induction therapy resulted in a recovery of immune status (CD4+ T-lymphocyte count 324 cells/mL) while the retinitis remained in active stage. With the recovery of immune status, the patient subsequently developed the signs of inflammation (IRU).

IRU most commonly develops in eyes with inactive or resolved CMV retinitis. Very rarely, it occurs in eyes with active CMV retinitis. In developing countries such as India, poor adherence to HAART is a major problem which leads to the increased risk of ocular complications in HIV patients. Thus, ophthalmological screening in HIV patients is important before initiating anti-retroviral therapy, to rule out any ocular opportunistic infections. Especially in case of CMV retinitis, anti-CMV induction therapy should be started before initiation of HAART to reduce the risk of adverse inflammatory reactions.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Figueiredo L, Rothwell R, Bilhoto M, Varandas R, Fonseca S. Immune recovery uveitis masked as an endogenous endophthalmitis in a patient with active CMV retinitis. Case Rep Ophthalmol Med 2013;2013:462968.  Back to cited text no. 1
Urban B, Bakunowicz-Łazarczyk A, Michalczuk M. Immune recovery uveitis: Pathogenesis, clinical symptoms, and treatment. Mediators Inflamm 2014;2014:971417.  Back to cited text no. 2
Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol 2005;140:509-16.  Back to cited text no. 3
McCannel CA, Holland GN, Helm CJ, Cornell PJ, Winston JV, Rimmer TG. Causes of uveitis in the general practice of ophthalmology. UCLA Community-Based Uveitis Study Group. Am J Ophthalmol 1996;121:35-46.  Back to cited text no. 4
Holbrook JT, Jabs DA, Weinberg DV, Lewis RA, Davis MD, Friedberg D, et al. Visual loss in patients with cytomegalovirus retinitis and acquired immunodeficiency syndrome before widespread availability of highly active antiretroviral therapy. Arch Ophthalmol 2003;121:99-107.  Back to cited text no. 5
Ortega-Larrocea G, Espinosa E, Reyes-Terán G. Lower incidence and severity of cytomegalovirus-associated immune recovery uveitis in HIV-infected patients with delayed highly active antiretroviral therapy. AIDS 2005;19:735-8.  Back to cited text no. 6
Kempen JH, Min YI, Freeman WR, Holland GN, Friedberg DN, Dieterich DT, et al. Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis. Ophthalmology 2006;113:684-94.  Back to cited text no. 7


  [Figure 1]


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