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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 32  |  Issue : 2  |  Page : 179-182

Atypical cytomegalovirus retinitis in an immunocompetent individual with diffuse large B-cell lymphoma posing a diagnostic enigma


1 Department of Ophthalmology, JIPMER Hospital, Puducherry, India
2 Department of Microbiology, JIPMER Hospital, Puducherry, India

Date of Submission22-Feb-2020
Date of Acceptance24-Feb-2020
Date of Web Publication25-Aug-2020

Correspondence Address:
Dr. Amit Kumar Deb
Department of Ophthalmology, Old IPD Block First Floor, JIPMER Hospital, Gorimedu, Puducherry - 605 006
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kjo.kjo_21_20

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  Abstract 


Cytomegalovirus (CMV) retinitis is a vision-threatening condition seen with CD4+ count below 50/μL. In the presence of systemic lymphoma, CMV retinitis may pose a diagnostic dilemma due to similar clinical features with intraocular lymphoma. We, hereby, report a rare case of bilateral CMV retinitis in a patient with normal CD4+ counts and a past history of diffuse large B-cell lymphoma (DLBCL). A 51-year-old male presented with sudden-onset painless diminution of vision in the right eye (RE) for a 2-week duration. He had a past history of DLBCL and had been treated with chemotherapy. On examination, his best-corrected visual acuity was perception of light in RE and 20/20 in the left eye (LE). RE fundus examination showed yellowish-white deep retinal lesions with scanty superficial retinal hemorrhages and perivascular exudates. LE fundus examination showed only one focal area of yellowish-white deep retinal lesions along the inferotemporal arcade. A provisional diagnosis of bilateral intraocular lymphoma was made based on the past history of systemic lymphoma. RE vitreous tap was done, and intravitreal injection of methotrexate was given. Vitreous sample revealed CMV DNA on polymerase chain reaction but no evidence of malignant cells on cytology. CD4 count was 393 cells/μl. The patient was subsequently treated with intravenous ganciclovir and oral valganciclovir for bilateral CMV retinitis. This case report highlights the importance of vitreous sample analysis in patients of systemic lymphoma presenting with atypical retinal necrotic lesions to establish an accurate diagnosis and to differentiate between closely mimicking lesions of intraocular lymphoma and viral retinitis.

Keywords: Cytomegalovirus retinitis, immunocompetent, intraocular lymphoma, normal CD4+ counts


How to cite this article:
Deb AK, Janani V S, Chowdhury SS, Chavhan P. Atypical cytomegalovirus retinitis in an immunocompetent individual with diffuse large B-cell lymphoma posing a diagnostic enigma. Kerala J Ophthalmol 2020;32:179-82

How to cite this URL:
Deb AK, Janani V S, Chowdhury SS, Chavhan P. Atypical cytomegalovirus retinitis in an immunocompetent individual with diffuse large B-cell lymphoma posing a diagnostic enigma. Kerala J Ophthalmol [serial online] 2020 [cited 2020 Sep 29];32:179-82. Available from: http://www.kjophthal.com/text.asp?2020/32/2/179/293289




  Introduction Top


Cytomegalovirus (CMV) retinitis is a vision-threatening condition seen commonly in individuals with acquired immunodeficiency syndrome when the CD4+ cell count falls below 50/μL. It can also manifest in other immunocompromised conditions such as post organ transplantation, autoimmune diseases, leukemia, lymphoma, and any other malignancy. In the setting of preexisting systemic lymphoma, CMV retinitis may pose a diagnostic dilemma due to its close resemblance to the clinical features of intraocular lymphoma.[1],[2] CMV retinitis has also been reported in immunocompetent individuals with high CD4+ count, albeit rare.[3] We, hereby, report such a rare case of bilateral CMV retinitis in a patient with a past history of diffuse large B-cell lymphoma (DLBCL) who presented with atypical and perplexing fundus features and with normal CD4+ counts.


  Case Report Top


A 51-year-old male presented with a history of sudden-onset painless diminution of vision in the right eye (RE) associated with floaters for a 2-week duration. He had been diagnosed with DLBCL 6 years ago and had achieved complete remission after successful treatment with chemotherapy. He had no systemic comorbidity and was not on immunosuppressives currently. His best-corrected visual acuity (BCVA) was perception of light (PL+) in RE and 20/20 in the left eye (LE). Anterior segment examination of RE showed circumcorneal congestion, 2+ cells in the anterior chamber, and a clear lens. Anterior segment examination of LE was normal. Fundus examination of the RE [Figure 1]a and b] showed Grade 1 vitritis, yellowish-white deep retinal lesions involving the posterior pole as well as peripheral retina, few superficial retinal hemorrhages, and perivascular exudates (frosted branch angiitis). Fundus examination of LE showed only one focal area of yellowish-white deep retinal lesions along the inferotemporal arcade [Figure 2]a and [Figure 2]b. Fundus picture in both eyes at presentation was atypical for intraocular lymphoma as well as CMV retinitis, thereby posing a diagnostic dilemma. However, an initial provisional diagnosis of bilateral intraocular lymphoma was made in view of the past history of systemic lymphoma (DLBCL) in our patient. He had undergone vitreous tap in the RE along with intravitreal injection of methotrexate (400 μg/0.1 ml). Investigations revealed negative enzyme-linked immunosorbent assay (ELISA) tests for human immunodeficiency virus (HIV) and toxoplasma, and negative Venereal Disease Research Laboratory test (VDRL) test for syphilis. CSF analysis and imaging ruled out a relapse of DLBCL. Vitreous sample analysis revealed CMV DNA on polymerase chain reaction (PCR) but no evidence of malignant cells on cytology. Blood sample was also positive for CMV DNA. CD4 cell count was 393 cells/μl. He was subsequently treated with intravenous ganciclovir 300 mg/day (5 mg/kg) BD for 2 weeks, followed by oral valganciclovir 900 mg OD. This was combined with twice weekly intravitreal ganciclovir (2 mg/0.1 ml) injections for 4 weeks in the RE. On subsequent follow-up examination 3 weeks later, fundus examination revealed healing lesions in RE [Figure 3]a and further progression of the lesions threatening to involve the fovea along with disc edema, peripapillary flame-shaped hemorrhages, and sheathing of vessels in LE [Figure 3]b. BCVA in RE was PL + and LE was 20/25 at this stage. Due to the progression of lesions in the LE, intravitreal ganciclovir (2 mg/0.1 ml) injections were given twice weekly for 3 weeks in LE as well. Three weeks later, LE fundus examination showed complete regression of the retinal lesions [Figure 4]. BCVA in LE was maintained at 20/25. Fundus examination in both eyes at the latest follow-up visit showed no further recurrence of the retinal lesions.
Figure 1: Fundus images of the right eye at presentation showing yellowish-white deep retinal lesions with scanty hemorrhages and frosted branch angiitis in the posterior pole (a) as well as the periphery (b)

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Figure 2: Fundus images of the left eye at presentation showing normal disc and macula (a), and focal retinal lesion (arrow mark) along the inferotemporal arcade (b)

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Figure 3: Fundus images at 3 weeks showing regressing retinal lesions in the right eye (a), and progressing retinal lesions threatening the fovea along with disc edema and peripapillary hemorrhages in the left eye (b)

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Figure 4: Fundus image of the left eye showing regressed retinal lesions

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  Discussion Top


CMV retinitis is the most common opportunistic eye infection seen in Human immunodeficiency virus positive (HIV +) individuals. It is also reported in other immunodeficiency states such as post organ transplantation, leukemia, and lymphoma. Rare reports of CMV retinitis in otherwise healthy individuals also do exist in literature. DLBCL is the most common subtype of non-Hodgkin's lymphoma seen in adults.[4] Our case describes such a rare occurrence of bilateral CMV retinitis in a patient with a past history of DLBCL with normal CD4 counts. Few other cases of CMV retinitis in patients with systemic lymphoma and normal CD4 counts [Table 1] have been reported previously in literature with a similar diagnostic dilemma as in our case.[1],[5],[6],[7]
Table 1: Cytomegalovirus retinitis in systemic lymphoma and normal CD4 count

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CMV retinitis manifests most often when CD4+ cell count is <50/μL. CD4+ cells are of two subtypes: memory subset (CD4+ CD45RO+) and naive subset (CD4+ CD45RA+). Memory cells are the ones that are pivotal in the prevention of CMV retinitis. These memory cells are more severely affected in cases of lymphoma/chemotherapy.[1] This may be a possible explanation of CMV retinitis in our patient despite normal CD4 cell counts.

Clinical features of CMV retinitis include a fulminant subtype presenting with dense, confluent areas of retinal whitening associated with retinal hemorrhages and vascular sheathing (frosted branch angiitis), and an indolent/granular subtype characterized by faint, grainy opacification, and little or no retinal hemorrhage without vascular sheathing.[4] Clinical features of intraocular lymphoma consist of vitritis, yellowish-white perivascular deep retinal lesions with or without hemorrhages, retinal vasculitis, or solitary or multiple creamy yellow or grayish subretinal masses. Findings in intraocular lymphoma can mimic various infective/inflammatory etiologies, for example, viral retinitis, toxoplasmosis, fungal chorioretinitis, and noninfectious choroiditis.[5],[8] In our case as well, the initial presenting fundus pictures were atypical for CMV retinitis. Confluent areas of yellowish-white retinal lesions with very scanty hemorrhages posed a diagnostic dilemma between intraocular lymphoma and viral retinitis. However, due to the past history of DLBCL, we considered intraocular lymphoma as the initial provisional diagnosis. PCR and cytology of the vitreous sample ruled out intraocular lymphoma and revealed the diagnosis of CMV retinitis. Based on the confirmed tissue diagnosis of CMV retinitis, the patient was treated subsequently with systemic and intravitreal ganciclovir injections. Visual acuity in the RE in our patient did not recover due to retinal atrophy at the macula post viral retinitis. Vision in the LE could, however, be salvaged due to accurate tissue diagnosis and timely intervention with systemic and intravitreal ganciclovir. Vitreous sample collection for PCR and cytology to rule out all infective etiologies and intraocular lymphoma, respectively, is, therefore, mandatory in all cases of systemic lymphoma presenting with retinal lesions.[9] Intravitreal methotrexate injections given for the treatment of suspected intraocular lymphoma can further worsen the CMV-associated retinal lesions. Therefore, timely intervention and accurate microbiological and cytological diagnosis is very essential to initiate appropriate treatment and salvage vision.

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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Chawla R, Venkatesh P, Garg SP, Mandal S, Tewari HK. Cytomegalovirus retinitis in a patient with non-Hodgkin's lymphoma: A diagnostic dilemma. Eur J Ophthalmol 2005;15:153-7.  Back to cited text no. 1
    
2.
Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program 2009;1:523-31.  Back to cited text no. 2
    
3.
Karkhaneh R, Lashay A, Ahmadraji A. Cytomegalovirus retinitis in an immunocompetent patient: A case report. J Curr Ophthalmol 2016;28:93-5.  Back to cited text no. 3
    
4.
Kang HM. Cytomegalovirus retinitis in patients with diffuse large B-cell lymphoma. J Retin 2017;2:97-100.  Back to cited text no. 4
    
5.
Derzko-Dzulynsky LA, Berger AR, Berinstein NL. Cytomegalovirus retinitis and low-grade non-Hodgkin's lymphoma: Case report and review of the literature. Am J Hematol 1998;57:228-32.  Back to cited text no. 5
    
6.
Svozílková P, Heissigerová J, Brichová M, Kalvodová B, Dvořák J, Ríhová E. A possible coincidence of cytomegalovirus retinitis and intraocular lymphoma in a patient with systemic non-Hodgkin's lymphoma. Virol J 2013;10:18.  Back to cited text no. 6
    
7.
Nasir MA, Jaffe GJ. Cytomegalovirus retinitis associated with Hodgkin's disease. Retina 1996;16:324-7.  Back to cited text no. 7
    
8.
Sandhu HS, Maguire AM. Atypical retinitis in the setting of prior cytomegalovirus retinitis. JAMA Ophthalmol 2016;134:709-10.  Back to cited text no. 8
    
9.
Tyagi M, Ambiya V, Mathai A, Narayanan R. Atypical cytomegalovirus retinitis in non-Hodgkin's lymphoma. BMJ Case Rep. 2015;2015. pii: bcr2015210812.  Back to cited text no. 9
    


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