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Clinical manifestations and immune markers of non-HIV-related CMV retinitis

BMC Infectious Diseases volume 24, Article number: 787 (2024) Cite this article

Abstract

Background

Since the HIV epidemic in the 1980s, CMV retinitis has been mainly reported in this context. CMV retinitis in persons living with HIV is usually observed when CD4 + cells are below 50 cells/mm3. This study aims to describe the immune markers of non-HIV-related CMV retinitis as well as to describe its clinical manifestations and outcomes.

Methods

Retrospective chart review of consecutive patients with CMV retinitis not related to HIV seen at the uveitis clinic of Jules Gonin Eye Hospital between 2000 and 2023. We reported the clinical manifestations and outcomes of the patients. We additionally assessed immune markers during CMV retinitis (leukocyte, lymphocyte, CD4 + cell and CD8 + cell counts as well as immunoglobulin levels).

Results

Fifteen patients (22 eyes) were included. Underlying disease was hematologic malignancy in 9 patients, solid organ transplant in 3 patients, rheumatic disease in 2 patients and thymoma in one patient. The median time between the onset of underlying disease and the diagnosis of retinitis was 4.8 years. Lymphopenia was observed in 8/15 patients (mild = 3, moderate = 4, severe = 1), and low CD4 counts were observed in 9/12 patients, with less than 100 cells/mm3 in 4 patients. Hypogammaglobulinemia was detected in 7/11 patients. Retinitis was bilateral in 7/15 patients, and severe visual loss was frequent (5/19 eyes). Disease recurrence was seen in 7/13 patients at a median time of 6 months after initial diagnosis. No differences in immune markers were observed in patients with vs. without recurrence.

Conclusion

CMV retinitis is a rare disorder that can affect patients suffering any kind of immunodeficiency. It is associated with a high visual morbidity despite adequate treatment. CD4 + cell counts are usually higher than those in HIV patients, but B-cell dysfunction is common.

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Background

Cytomegalovirus (CMV) is a double-stranded DNA virus from the Herpesviridae family. The seroprevalence of CMV infection in the population is estimated to be between 50 and 100%. [1] Retinitis is a sight-threatening condition and represents one of the most severe presentations of CMV infection. Since the HIV epidemic in the 1980s, CMV retinitis has been mainly reported in this context. CMV retinitis in persons living with HIV (PLWH) is usually observed when CD4 + cells are below 50 cells/mm3 and represents one of the most frequent opportunistic infections defining AIDS [2] . Even though most of the literature on CMV retinitis is HIV-related, CMV retinitis due to iatrogenic immunosuppression has been known since the forties [3]. The immune response to CMV infection and the mechanism of CMV reactivation remain poorly understood. Whereas the role of CD4 + and CD8 + T lymphocytes in the control of CMV infection has been largely demonstrated, the impact of the use of immunosuppressive drugs impairing humoral immunity on the incidence of CMV retinitis has been less reported [4].

This study aims to describe the clinical characteristics, immune markers and clinical outcomes of non-HIV-related CMV retinitis in a cohort of patients seen in our outpatient clinics over the last two decades.

Methods

This is a retrospective study of consecutive patients treated for non-HIV-related CMV retinitis between 2000 and 2023 in the uveitis clinic of Jules-Gonin Eye Hospital in Lausanne, Switzerland. The study was conducted in compliance with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board (CER-VD n° 2018–02161) for retrospective analysis between 2000 and 2022. For later inclusion all patient had signed the informed consent allowing data analysis for research purpose (CER-VD PB 2016 − 00868).

Written informed consent was obtained from all living patients, for deceased patient, the use of data was approved by the above-mentioned ethic committee.

CMV retinitis diagnosis was based on the SUN (Standardized Uveitis Nomenclature study group) classification criteria. [5] Briefly, it was suspected based on the presence of a retinal necrotic lesion with indistinct borders and small satellite lesions in the context of immunosuppression. It was confirmed either by a PCR on aqueous humor after anterior chamber tap or by the presence of additional clinical characteristics (wedge-shaped lesion, hemorrhagic retinitis and/or granular appearance) associated with a confirmed systemic CMV infection. All the included patient had a negative antigenic and serologic test for HIV infection.

Demographic data collection included age, sex, systemic disease, immunosuppressive therapy, delay of onset of CMV retinitis after introduction of immunosuppression (in autoimmune disease or after solid organ transplantation) or chemotherapy in hematologic malignancies, laterality of eye involvement, and type and duration of antiviral therapy. Clinical data collected included best corrected visual acuity (BCVA) using the decimal chart. The zonal distribution of the lesions was evaluated according to Holland et al. [6], where zone 1 refers to an area of 3000 μm (2 disc diameters) from the fovea or 1500 μm from the edge of the optic nerve head, zone 2 extends up to the equator and zone 3 is the area beyond the equator. The extent of the lesion was expressed in clock-hours of retinal involvement. The presence of complications (retinal detachment, ischemia, etc.) was also reported. Follow-up data were described in patients with a follow-up longer than 6 months and included final BCVA, number of recurrences, antiviral prophylaxis duration and, if applicable, time to death.

Laboratory data collected included the number of CMV copies measured by quantitative polymerase chain reaction (qPCR) in the peripheral blood, in the aqueous humor and in the cerebrospinal fluid when appropriate (CSF) (in one case). The total leucocyte count was reported as well as the lymphocyte, CD4+, CD8 + and CD19+ (B-lymphocytes) counts. Leukopenia was classified into mild (3 - < 4 G/L), moderate (< 3–2 G/L) and severe (< 2 G/L) forms according to an adapted classification from the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTAE). [7] Similarly, lymphopenia was graded into mild (500–1000 cells/mm3), moderate (200–499 cells/mm3) and severe (< 200 cells/mm3) forms. Gammaglobulin levels were also reported, and hypogammaglobulinemia was classified into severe (< 3.5 G/L) and moderate (3.5-5 G/L) forms [8].

Categorical variables were expressed as numbers (percentages). For continuous variables, the median and range were reported. The Wilcoxon-Mann‒Whitney test was used to compare the results. A p value < 0.05 was considered statistically significant.

Results

Fifteen consecutive patients (22 eyes) were included in the study. This represents an incidence rate of 0.49% of uveitis cases in our tertiary referral center. The median age was 66 years (IQR 14). Seven patients were males (46.7%). Systemic diagnosis was hematologic malignancies in 9 patients (60%), solid organ transplant (SOT) in 3 patients (20%), rheumatic disease in 2 patients (systemic lupus erythematosus (SLE) and rheumatoid arthritis) (13.3%), and one patient presented with a thymoma and Good syndrome (Table 1)(6.7%).

Table 1 Demographic data, systemic diagnosis and treatment
Full size table

The median time between systemic diagnosis or SOT and retinitis was very variable (4.8 years, IQR 8.4 years). Patients with autoimmune diseases presented the longest disease duration prior to the onset of retinitis (47.8 and 25.4 years, respectively) as opposed to heart transplant recipients who presented with CMV retinitis 4 and 8 months, respectively, after transplantation (Table 1).

CMV retinitis was bilateral in 7 patients (46.7%). The zonal distribution and extent of the lesions are depicted in Table 2. Initial BCVA was severely impaired (≤ 1/10 BCVA) in 4/22 eyes (18.2%).

Table 2 Ophthalmological characteristics and follow up data
Full size table

CMV DNA in peripheral blood was present in 11/13 patients (84.6%). It was known prior to the diagnosis of CMV retinitis in 6/13 patients (46.2%), discovered at the time of CMV retinitis in 5/13 patients (38.5%) and remained negative in 2/13 patients (15.4%).

The main laboratory features at the time of diagnosis are depicted in Table 3. The median leucocyte count was 5 G/L (IQR 3.4), with severe leukopenia present in 2 patients (13.3%). The median lymphocyte count was 846 cells/mm3 (IQR 993), with only two patients presenting severe lymphopenia (13.3%), and the median CD4 count was 348 cell/m3 (IQR 407), with 4/12 patients with counts lower than 100 cell/mm3 (33.3%). A CD8 + count lower than 400 cell/mm3 was present in 6 patients (50%), with no data for 3 patients. The median gammaglobulin level was 5.43 G/L (IQR 6.25), with hypogammaglobulinemia present in 7 out of 11 patients (63.6%).

Table 3 Laboratory features at the time of CMV retinitis diagnosis
Full size table

Initial treatment was oral valganciclovir (900 mg bid adjusted to the renal function) in 12 cases (80%) or intravenous ganciclovir (5 mg/kg bid) in 1 case (6.7%). Patients 2 and 6 initially received alternative treatments (foscarnet, 60 mg/kg/day TID and/or 5 mg/kg/week cidofovir) because of a known systemic ganciclovir-resistant CMV infection (proven in patient 6 by a mutation N408K in the UL54 gene). Induction therapy was given until full scarring of the lesion for a median time of 30 days (range 21–90 days). It was followed by maintenance therapy of 7 months (range from 3 weeks in one patient presenting with pancytopenia to 24 months). Two patients received adjuvant intravitreal foscarnet injections (1.2 mg in 0.05 mL): patient number 4 because of pancytopenia and patient number 6 because of a known ganciclovir-resistant virus.

Two patients were excluded from the follow-up analysis (follow-up of less than 6 months). The median follow-up after diagnosis was 1.9 years (IQR 1.9) (Table 2). Seven patients (53.8%) died during the follow-up at a median time of 2.1 years (IQR 2.55) after retinitis diagnosis. Of the 7 patients, 2 (15.4%) died during the first year after the diagnosis. The number of deaths corresponded to a rate of 0.06 patients/year.

Recurrence occurred in 7 patients (53.8%) after a median time of 6 months after initiation of therapy (IQR 6). Three of those patients presented multiple recurrences (four recurrences for patient 6 and two recurrences for patients 10 and 13). The calculated recurrence rate was 24% recurrences per patient/year. Four patients were still under valganciclovir maintenance therapy (450 mg BID) at the time of recurrence. From the 7 patients with recurrence, four responded well to increased dosage of ganciclovir, one patient had a known resistant strain and was treated with cidofovir and two patients (number 5 and 10) were suspected to have to ganciclovir resistant virus because of progression of the disease under therapeutic dosage. Both responded well to alternative treatments (Foscavir and cidofovir respectively). The other three had stopped the antiviral treatment: 2 months earlier in 2 patients and one month earlier in the third. Of the 19 eyes with CMV retinitis, BCVA at last follow-up was severely impaired (≤ 1/10) and moderately impaired (2/10 − 5/10) in 4 (21.1%) and 7 (36.8%) eyes, respectively. Ocular complications included retinal detachment in 4 eyes (21.1%), retinal ischemia and/or vascular occlusion in 2 eyes (10.5%), macular edema due to immune recovery in 4 eyes (2 patients, 21.1%) and foveal extension of the retinitis in one case.

There were no statistically significant differences in lymphocyte and CD4 counts or globulin levels in patients with or without relapse (Table 4).

Table 4 Immune markers in patients with and without relapse of CMV retinitis
Full size table

Discussion

This study presents the data of 15 patients (22 eyes) with non-HIV-related CMV retinitis. Supporting the results of other series, we found hematological malignancies to be the most frequent systemic diagnoses associated with CMV retinitis [9]. Nevertheless, CMV retinitis can also be found in long-lasting rheumatismal diseases or after solid organ transplant [10].

The presentation of CMV retinitis in our series was often severe. We found zone 1 involvement in 36.4% of the eyes and an extension of over one-quarter of the retina in 45.5% of the eyes. Initial visual acuity below 5/10 was present in 40.9%. These results correspond to the current literature, which reports rates of zone 1 involvement in non-HIV-related CMV retinitis to vary between 33% and 61% [9,10,11,12]. We found that CMV retinitis in hematological malignancies more frequently presented bilateral involvement and a zone 1 extension of the lesions, in line with the results of a previous study [13].

The immune status of our patients was different from those found in HIV-related CMV retinitis. Whereas CMV retinitis is rarely seen in PLWH with CD4 + counts over 50 cell/mm3 and virtually never in patients with CD4 + counts over 100 cell/mm3, we found that only four patients (33.3%) had CD4 + counts under 100 cell/mm3. We found one series reporting CD4 + counts under 100 cell/mm3 in non-HIV-related CMV retinitis in 48% of their patients without details on the lymphocyte counts or immunoglobulin levels [12]. The total lymphocyte and CD4 + cell counts observed in our cohort are in line with previous publications of SOT and HSCT recipients with systemic CMV disease. After heart transplantation, a median lymphocyte count of 380 cell/mm3 was found in patients who developed early CMV disease compared to 840 cell/mm3 in patients without CMV disease [14]. Likewise, lymphopenia was identified as an independent risk factor for CMV disease after renal transplantation [15]. However, there are incomplete data on the level of immune parameters specifically for SOT recipients with CMV retinitis.

We also observed that immunoglobulin levels were reduced in 63.6% of the patients who were tested, a rate that was much higher than that usually found after SOT (45%) or after HSCT (32.5%). [16, 17] Hypogammaglobulinemia has been associated with an increased risk of CMV disease in these populations, [16, 18, 19]. In PLWH, gammaglobuline levels are frequently increased and hypogammaglobulinemia is a rare finding which is not known to be associated with CMV disease [20,21,22,23]. Given the uncontrolled nature of our study, we cannot exclude hypogammaglobulinemia as a marker of severity of the underlying disease rather than a risk factor for CMV retinitis. Therefore, the role of the substitution of immunoglobulins in these patients also remains under debate [24, 25].

Testing for CMV DNA in the blood by qPCR is a useful tool for the monitoring and detection of systemic CMV disease. The combination of a positive PCR test in the blood and visual symptoms should trigger a rapid ophthalmological evaluation. However, as shown for CMV colitis, our series demonstrated that 15.4% of our patients did not have CMV viremia, highlighting the necessity to maintain a high clinical suspicion for CMV retinitis in immunosuppressed patients even in the absence of signs of non-ophthalmic organ involvement of CMV disease. Early diagnosis remains a key feature for good visual outcome [26, 27]. Monitoring the CMV specific immune response might be a promising alternative to predict the risk of CMV disease, although the performance of these assays for predicting CMV retinitis has not been largely investigated [28, 29].

The prognosis of CMV retinitis is serious, with one-third of patients with severe visual loss at the final visit and half of the patients with recurrence in our series. These rates match most of the published series in non-HIV-related CMV retinitis [9, 10, 12]. One exception is a prospectively followed cohort of patients with hematological malignancies and CMV retinitis reporting a lower recurrence rate (16.7%), which might be explained by the inclusion of asymptomatic, less severe CMV retinitis (48% of the patients). [27] The mortality rate was also high (overall 53.8%, 15.4% at one year) but was lower than the rates reported in the literature (30.3% at one year in HSCT with CMV retinitis). [27]

In our study, due to the modest sample size, we were not able to correlate the use of a specific immunosuppressive drug and the risk for a worse outcome of CMV retinitis. It is, however, worth noting that all but three patients were taking two or more immunosuppressant drugs described as risk factors for CMV disease in the literature [30, 31].

Recurrence occurred in 42.8% of the cases under prophylactic treatment (3/7 cases). It is unknown whether these recurrences are related to a dose reduction of the prophylactic treatment due to systemic toxicity or to the development of drug-resistant strains. In any case, it highlights the need for alternative prophylactic treatments. New drugs have recently been developed for CMV prophylaxis and therapy, including letermovir and maribavir. Because maribavir does not cross the hematoencephalic barrier, it cannot be used for the treatment of CMV retinitis. Letermovir is currently used for CMV prophylaxis in HSCT recipients. Given the potential toxicity of long-term prophylaxis with valganciclovir, this drug can be an option for secondary prophylaxis to avoid relapse of CMV retinitis.

The main limitation of this study is the restricted number of patients and the retrospective nature of the study. Even though all patients had an iatrogenic immunosuppression, the different nature of the underlying diseases and treatments do not allow a direct comparison. Follow-up were also variable as well as the duration of prophylactic treatments. A prospective investigation of gammaglobuline levels, lymphocyte number and function should be perform to confirm our findings.

In conclusion, CMV retinitis is a rare disease affecting immunosuppressed patients. It is associated with a high mortality rate and a high morbidity rate. Compared with HIV-related CMV retinitis, phenotyping of lymphocytes revealed less frequently reduced CD4 + and CD8 + counts. Hypogammaglobulinemia was very frequent, but its significance requires further investigation.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 2010;20(4):202–13.

    Article  PubMed  Google Scholar 

  2. Kuppermann BD, Petty JG, Richman DD, Mathews WC, Fullerton SC, Rickman LS, et al. Correlation between CD4 + counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus-related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syndrome. Am J Ophthalmol. 1993;115:575–82.

    Article  PubMed  CAS  Google Scholar 

  3. Bhat P, Jackson AT, Foster CS. Infectious uveitis. In: Ocular Disease [Internet]. Elsevier; 2010 [cited 2022 Apr 29]. pp. 654–65. https://linkinghub.elsevier.com/retrieve/pii/B9780702029837000838.

  4. Manuel O, Avery RK. Update on cytomegalovirus in transplant recipients: new agents, prophylaxis, and cell-mediated immunity. Curr Opin Infect Dis. 2021;34(4):307–13.

    Article  PubMed  CAS  Google Scholar 

  5. Standardization of Uveitis Nomenclature (SUN) Working Group. Classification criteria for Cytomegalovirus Retinitis. Am J Ophthalmol. 2021;228:245–54.

    Article  Google Scholar 

  6. Holland GN, Buhles WC, Mastre B, Kaplan HJ. A controlled retrospective study of ganciclovir treatment for cytomegalovirus retinopathy. Use of a standardized system for the assessment of disease outcome. UCLA CMV retinopathy. Study Group. Arch Ophthalmol Chic Ill 1960. 1989;107(12):1759–66.

    CAS  Google Scholar 

  7. Cancer Therapy Evaluation Program, Co. Common Terminology Criteria for Adverse Events [Internet]. 2006 [cited 2022 Apr 29]. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf.

  8. Mawhorter S, Yamani MH. Hypogammaglobulinemia and infection risk in solid organ transplant recipients. Curr Opin Organ Transpl. 2008;13(6):581–5.

    Article  Google Scholar 

  9. Iu LP, Fan MC, Lau JK, Chan TS, Kwong YL, Wong IY. Long-term follow-up of Cytomegalovirus Retinitis in Non-HIV Immunocompromised patients: clinical features and visual prognosis. Am J Ophthalmol. 2016;165:145–53.

    Article  PubMed  Google Scholar 

  10. Kuo IC, Kempen JH, Dunn JP, Vogelsang G, Jabs DA. Clinical characteristics and outcomes of cytomegalovirus retinitis in persons without human immunodeficiency virus infection. Am J Ophthalmol. 2004;138(3):338–46.

    Article  PubMed  Google Scholar 

  11. Jeon S, Lee WK. Cytomegalovirus retinitis in a human immunodeficiency virus-negative cohort: long-term management and complications. Ocul Immunol Inflamm. 2015;23(5):392–9.

    Article  PubMed  Google Scholar 

  12. Sadik MT, Aksu Ceylan N, Cebeci Z, Kir N, Oray M, Tugal-Tutkun I. Patterns of cytomegalovirus retinitis at a tertiary referral center in Turkey. Int Ophthalmol. 2021;41(9):2981–92.

    Article  PubMed  Google Scholar 

  13. Son G, Lee JY, Kim JG, Kim YJ. Clinical features of cytomegalovirus retinitis after solid organ transplantation versus hematopoietic stem cell transplantation. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol. 2021;259(3):585–91.

    Article  Google Scholar 

  14. Yoon M, Oh J, Chun KH, Lee CJ, Kang SM. Post-transplant absolute lymphocyte count predicts early cytomegalovirus infection after heart transplantation. Sci Rep. 2021;11(1):1426.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Corona-Nakamura AL, Monteón-Ramos FJ, Troyo-Sanromán R, Arias-Merino MJ, Anaya-Prado R. Incidence and Predictive Factors for Cytomegalovirus Infection in Renal Transplant Recipients. Transplant Proc. 2009;41(6):2412–5.

  16. Florescu DF, Kalil AC, Qiu F, Schmidt CM, Sandkovsky U. What is the impact of hypogammaglobulinemia on the rate of infections and survival in solid organ transplantation? A Meta-analysis: risk of infections in severe hypogammaglobulinemia. Am J Transpl. 2013;13(10):2601–10.

    Article  CAS  Google Scholar 

  17. Karakulska-Prystupiuk E, Dwilewicz-Trojaczek J, Drozd-Sokołowska J, Kmin E, Chlebus M, Szczypińska K, et al. Prevalence of hypogammaglobulinemia and its management with subcutaneous immunoglobulin supplementation in patients after allogeneic hematopoietic stem cell transplantation—a single-center analysis. Ann Hematol. 2021;100(12):3007–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Deborska-Materkowska D, Perkowska-Ptasinska A, Sadowska A, Gozdowska J, Ciszek M, Serwanska-Swietek M, et al. Diagnostic utility of monitoring cytomegalovirus-specific immunity by QuantiFERON-cytomegalovirus assay in kidney transplant recipients. BMC Infect Dis. 2018;18(1):179.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Carbone J, Rodriguez-Ferrero ML, Lopez-Hoyos M, Karanovic B, Arias M, Rodrigo E et al. IgG Hypogammaglobulinemia is a Risk Factor of Cytomegalovirus Infection in a Multicenter Study in Kidney Transplantation. Transplantation [Internet]. 2018;102. https://journals.lww.com/transplantjournal/Fulltext/2018/07001/IgG_Hypogammaglobulinemia_is_a_Risk_Factor_of.573.aspx.

  20. Chess Q, Daniels J, North E, Macris NT. Serum immunoglobulin elevations in the acquired immunodeficiency syndrome (AIDS): IgG, IgA, IgM, and IgD. Diagn Immunol. 1984;2(3):148–53.

    PubMed  CAS  Google Scholar 

  21. Konstantinopoulos PA, Dezube BJ, Pantanowitz L, Horowitz GL, Beckwith BA. Protein electrophoresis and Immunoglobulin Analysis in HIV-Infected patients. Am J Clin Pathol. 2007;128(4):596–603.

    Article  PubMed  CAS  Google Scholar 

  22. Nozarian Z, Mehrtash V, Abdollahi A, Aeinehsazi S, Khorsand A, Eftekhar-Javadi A, et al. Serum protein electrophoresis pattern in patients living with HIV: frequency of possible abnormalities in Iranian patients. Iran J Microbiol. 2019;11(5):440–7.

    PubMed  PubMed Central  Google Scholar 

  23. Zemlin AE, Ipp H, Maleka S, Erasmus RT. Serum protein electrophoresis patterns in human immunodeficiency virus-infected individuals not on antiretroviral treatment. Ann Clin Biochem. 2015;52(Pt 3):346–51.

    Article  PubMed  CAS  Google Scholar 

  24. Ohmoto A, Fuji S, Shultes KC, Savani BN, Einsele H. Controversies about immunoglobulin replacement therapy in HSCT recipients with hypogammaglobulinemia. Bone Marrow Transpl. 2022;57(6):874–80.

    Article  CAS  Google Scholar 

  25. Florescu DF, Kalil AC, Qiu F, Grant W, Morris MC, Schmidt CM, et al. Does increasing immunoglobulin levels impact survival in solid organ transplant recipients with hypogammaglobulinemia? Clin Transpl. 2014;28(11):1249–55.

    Article  CAS  Google Scholar 

  26. Mori T, Mori S, Kanda Y, Yakushiji K, Mineishi S, Takaue Y, et al. Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transpl. 2004;33(4):431–4.

    Article  CAS  Google Scholar 

  27. Kim JY, Hong SY, Park WK, Kim RY, Kim M, Park YG, et al. Prognostic factors of cytomegalovirus retinitis after hematopoietic stem cell transplantation. PLoS ONE. 2020;15(9):e0238257.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Prakash K, Chandorkar A, Saharia KK. Utility of CMV-Specific Immune monitoring for the management of CMV in solid organ transplant recipients: a clinical update. Diagnostics. 2021;11(5):875.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Yong MK, Lewin SR, Manuel O. Immune monitoring for CMV in transplantation. Curr Infect Dis Rep. 2018;20(4):4.

    Article  PubMed  Google Scholar 

  30. Mavropoulou E, Ternes K, Mechie NC, Bremer SCB, Kunsch S, Ellenrieder V, et al. Cytomegalovirus colitis in inflammatory bowel disease and after haematopoietic stem cell transplantation: diagnostic accuracy, predictors, risk factors and disease outcome. BMJ Open Gastroenterol. 2019;6(1):e000258.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wagner M, Earley AK, Webster AC, Schmid CH, Balk EM, Uhlig K. Mycophenolic acid versus azathioprine as primary immunosuppression for kidney transplant recipients. Cochrane Kidney and Transplant Group, editor. Cochrane Database Syst Rev [Internet]. 2015 Dec 3 [cited 2022 Sep 2]; https://doi.org/10.1002/14651858.CD007746.pub2.

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Acknowledgements

not applicable.

Funding

This study was supported by AURIS Foundation, W & E. Grand dʼHauteville Foundation, Ingvar Kamprad Fund, Fleurette Wagemakers, Foundation, Kononchuk Family Grant, Blatter Family Grant and Rhumatismes-Enfants-Suisse Foundation support Financial disclosure: No financial disclosures.

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Author notes

  1. Olga Passarin and Florence Hoogewoud contributed equally as co-first authors.

Authors and Affiliations

  1. Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, avenue de France 15, Lausanne, 1002, Switzerland

    Olga Passarin, Florence Hoogewoud & Yan Guex-Crosier

  2. Cabinet ophtalmologique, Av. de la Gare 52, Lausanne, 1003, Switzerland

    Olga Passarin

  3. Department of Infectiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, 1011, Switzerland

    Oriol Manuel

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OP and FH contributed equally to the work as first authors.

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Correspondence to Yan Guex-Crosier.

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The study was conducted in compliance with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board (Comission cantonale d’éthique sur la recherche sur l’être humain; CER-VD n° 2018–02161). Written informed consent was obtained from all living patients, for deceased patient, the use of data was approved by the above-mentioned ethic committee.

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The data have been presented at the Swiss Ophthalmology Congress in August 2022 and the French Ophthalmology Congress in May 2023.

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Passarin, O., Hoogewoud, F., Manuel, O. et al. Clinical manifestations and immune markers of non-HIV-related CMV retinitis. BMC Infect Dis 24, 787 (2024). https://doi.org/10.1186/s12879-024-09653-x

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