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Cytomegalovirus Retinitis

Cytomegaloviral Retinitis

Cytomegalovirus (CMV) retinitis is usually an opportunistic viral infection, found in individuals with low immunity. This condition results in the inflammation of the retina, and can eventually lead to blindness.


Presentation

Cytomegalovirus infection commonly occurs in adults during their fourth decade of life. The retina can be affected when the virus spreads via the bloodstream [1]. People infected with the human immunodeficiency virus (HIV) are at a higher risk of acquiring cytomegalovirus retinitis, as the former organism compromises the endothelial integrity of vasculature, and blood flow, in the retina [2]. Retinitis may involve inflammation as well as bleeding of the retina, often in the ocular fundus. Lesions such as cotton wool spots can be visualized on the retina.

HIV further predisposes individuals to cytomegalovirus retinitis due to its immunosuppressive effects. This results in activation of latent infection after the host immunity decreases [3]. Various conditions, such as diabetes mellitus, malignancy, and organ transplantation, impart the same effect [4] [5]. Although cytomegalovirus retinitis in immunocompetent individuals is rare, cases have been reported. It has also been described in patients with systemic lupus erythematosus and other autoimmune diseases, with concomitant use of immunosuppressive drugs [6].

Cytomegalovirus retinitis can be asymptomatic. In symptomatic infection, patients may experience various visual disturbances, including floaters, photopsia, narrowed visual fields, blurred vision, and scotoma [7]. They do not usually complain of red or painful eyes. Blindness can ensue within months of symptom onset. Furthermore, cytomegalovirus retinitis is often initially unilateral before becoming bilateral.

Notably, immunocompromised children do not seem to have increased susceptibility to this disease [8]. Cytomegalovirus retinitis can also be congenital, occurring in 25% of babies already exhibiting other features of CMV infection, and does not usually worsen after birth.

Recurrent Bacterial Infection
  • Patients with CVID are mainly characterized by decreased serum immunoglobulin levels, and increased susceptibility to recurrent bacterial infections, autoimmune disorders, and malignancies.[ncbi.nlm.nih.gov]
Retinal Hemorrhage
  • Retinal examination uncovered classical appearance of retinal whitening and retinal hemorrhages with extensive macular involvement. CMV retinitis can occur as a late complication following liver transplantation.[ncbi.nlm.nih.gov]
  • A, Retinal hemorrhages and areas of opaque retina are present. Note the vascular sheathing in the superotemporal arcade and hard exudates in the macular region. B, Histologically, full-thickness retinal necrosis is present.[aao.org]
  • White, fluffy retinal necrosis with overlying retinal hemorrhages.[eyerounds.org]
  • The retinitis is detected with ophthalmoscopy as either a perivascular yellow-white retinal lesion frequently associated with retinal hemorrhage or as a focal white granular infiltrate, often without hemorrhage.[annals.org]
Retinal Pigmentation
  • (n 3 eyes) characterized by inner retinal hyperreflectivity, large empty spaces in outer nuclear layer, and bridges of retinal tissue but retinal pigment epithelium and choriocapillaris sparing.[ncbi.nlm.nih.gov]
  • These findings suggested inflammation or scarring of the choroid and retinal pigment epithelial injury. Indocyanine green angiographic findings in this cytomegalovirus retinitis patient suggested a cytomegalovirus retinitis lesion of the choroid.[ncbi.nlm.nih.gov]
  • In the late to subacute stage, features observed included rhegmatogenous retinal detachment with shrinking posterior hyaloid membrane and waving from the ellipsoid zone to the retinal pigment epithelium.[ncbi.nlm.nih.gov]
  • To evaluate the association of sequence variability of depicted viral genes with HCMV retinitis and in vitro growth properties in retinal pigment epithelial cells (RPE) and human foreskin fibroblasts (HFF), we compared 14 HCMV isolates obtained from vitreous[ncbi.nlm.nih.gov]
  • There were also alternating areas of stippled hyperfluorescence and hypofluorescence at places suggestive of retinal pigment epithelium atrophy. FFA of left eye was normal.[mjdrdypu.org]
Retinal Pigmentation
  • (n 3 eyes) characterized by inner retinal hyperreflectivity, large empty spaces in outer nuclear layer, and bridges of retinal tissue but retinal pigment epithelium and choriocapillaris sparing.[ncbi.nlm.nih.gov]
  • These findings suggested inflammation or scarring of the choroid and retinal pigment epithelial injury. Indocyanine green angiographic findings in this cytomegalovirus retinitis patient suggested a cytomegalovirus retinitis lesion of the choroid.[ncbi.nlm.nih.gov]
  • In the late to subacute stage, features observed included rhegmatogenous retinal detachment with shrinking posterior hyaloid membrane and waving from the ellipsoid zone to the retinal pigment epithelium.[ncbi.nlm.nih.gov]
  • To evaluate the association of sequence variability of depicted viral genes with HCMV retinitis and in vitro growth properties in retinal pigment epithelial cells (RPE) and human foreskin fibroblasts (HFF), we compared 14 HCMV isolates obtained from vitreous[ncbi.nlm.nih.gov]
  • There were also alternating areas of stippled hyperfluorescence and hypofluorescence at places suggestive of retinal pigment epithelium atrophy. FFA of left eye was normal.[mjdrdypu.org]
Retinal Scar
  • Fibrovascular changes occurred in the CMV retinitis scar, were misdiagnosed as CMV retinitis reactivation, and were treated with anti-CMV medication.[ncbi.nlm.nih.gov]
  • Eyes with Full thickness retinitis developed choriocapillaris atrophy and choroidal thinning and retinal scars as the lesions healed. CONCLUSION: There are two distinct patterns of chorioretinal involvement in CMV retinitis.[ncbi.nlm.nih.gov]
  • Two patients were not treated (patients 1 and 8), one of whom (patient 8) had received an autologous transplant and was diagnosed with atrophic retinal scarring compatible with previous CMV active retinitis after spontaneous resolution of the acute retinitis[academic.oup.com]
  • In recovered patients, hemorrhage and exudation were disappeared completely and yellow-white retinal scars were formed in 10 eyes.[bmcinfectdis.biomedcentral.com]
Unilateral Blindness
  • However, there is a risk of unilateral blindness in severe cases.[patient.info]

Workup

The ophthalmologic examination is the diagnostic procedure employed. This involves dilating the pupils to visualize internal ocular structures through ophthalmoscopy.

CMV infection can be detected through biochemical analysis of blood and urine samples. Furthermore, a biopsy would reveal viral organisms in the tissue, however, this is not a routine procedure.

It is good practice to screen all patients at risk of cytomegalovirus retinitis, including those that lack symptoms, because early stage diagnosis and treatment are uncomplicated, and in addition, a significant proportion of individuals are asymptomatic at the time of diagnosis. Furthermore, intervention prevents blindness, which is a highly debilitating sequela of cytomegalovirus retinitis. Screening via testing visual acuity of patients using a Snellen chart is insufficient, as only a small portion of the retina, the fovea, is assessed in this way. The use of questionnaires specifically tailored to detect or elicit signs and symptoms of cytomegalovirus retinitis can be a more effective screening tool.

HIV patients have a higher risk of cytomegalovirus retinitis, and it is reported that the latter is the most frequently encountered opportunistic viral infection in the above group, especially when CD4 (cluster of differentiation 4) cell count is extremely low, that is, less than 50 per cubic millimeter [9]. Immunocompetent individuals, especially those who have received steroid injections, make up the minority of cytomegalovirus retinitis patients [10] [11].

Lymphocytopenia
  • The authors report a case of CMV retinitis in an HIV-negative man with idiopathic CD4 lymphocytopenia (ICL). This is the first such case to be confirmed by polymerase chain reaction (PCR) of aqueous humor. Case report.[ncbi.nlm.nih.gov]
  • We describe the case of a 16-month-old girl with neuroblastoma and chronic lymphocytopenia due to chemotherapy and treosulfan-containing megatherapy who developed cytomegalovirus retinitis and neuritis.[ncbi.nlm.nih.gov]
  • Analysis of blood samples disclosed a marked selective CD4 T-cell lymphocytopenia, with a reduced CD4/CD8 ratio of 0.25 (reference range, 0.66-3.52) but a normal B cell count.[jamanetwork.com]
  • His CD4 and CD8 percentages were 7.01% and 83.19%, respectively, with CD4/CD8 ratio of 0.08 suggestive of isolated CD4 lymphocytopenia. Chest imaging and pulmonary function test revealed normal study.[meajo.org]
  • Lippincott-Raven (pg. 215 - 27 ) 9 Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study , Blood , 1996 , vol. 88 (pg. 4063 - 71 ) 10 Lymphocytopenia[academic.oup.com]
Lymphocytic Infiltrate
  • Here we present a CVID patient who has developed a clinical polyclonal lymphocytic infiltration phenotype associated with severe and irreversible pancytopenia with unknown etiology.[ncbi.nlm.nih.gov]
  • Viral infection also induces CXCL9 and CXCL10, which are known T-cell chemoattractants that precede lymphocyte infiltration.[doi.org]

Treatment

  • Treatment was again withheld after diagnosis of retinitis because of immunocompetent status, potential side effects of ganciclovir treatment, and location of retinitis in the retinal periphery of both eyes.[ncbi.nlm.nih.gov]
  • To our knowledge, this is the first report of a successful treatment of co-infection with Nocardia pneumonia and cytomegalovirus retinitis in a renal transplant patient, with early diagnosis and prompt treatment.[ncbi.nlm.nih.gov]
  • Cytomegalovirus retinitis can be a sight-threatening complication of immunosuppressive treatment with FK 506. Ganciclovir treatment together with a reduction in FK 506 dose was effective in preserving vision.[ncbi.nlm.nih.gov]
  • Forty-one eyes (61.2 %) completely resolved after treatment within the 6-month follow-up.[ncbi.nlm.nih.gov]
  • To describe leflunomide use in the treatment of drug resistant cytomegalovirus retinitis. Leflunomide has been shown to be effective in the treatment of systemic CMV viremia.[ncbi.nlm.nih.gov]

Prognosis

  • CONCLUSION: The overall visual prognosis and the clinical features of CMV retinitis do not differ between HIV and non-HIV patients. The visual prognosis of CMV retinitis still remains quite poor despite advancements in antiviral treatment.[ncbi.nlm.nih.gov]
  • Treatment and prognosis The treatment for CMV retinitis involves administration of antiviral medications (e.g. valganciclovir, ganciclovir, foscarnet, or cidofovir).[radiopaedia.org]
  • […] infection of the eye, a common opportunistic infection in AIDS, a complication of disseminated CMV infection Clinical Retinal inflammation, blindness Management Antivirals–eg, foscarnet, cidofovir, gancyclovir, systemically and as a ganciclovir implant Prognosis[medical-dictionary.thefreedictionary.com]
  • SUMMARY The incidence and prognosis of CMV retinitis has improved remarkably since the introduction of HAART in 1996. Treatment is tailored to the individual, involving localized and systemic anti-CMV therapy.[retinalphysician.com]
  • There is no treatment but the prognosis is excellent.[patient.info]

Etiology

  • Here we present a CVID patient who has developed a clinical polyclonal lymphocytic infiltration phenotype associated with severe and irreversible pancytopenia with unknown etiology.[ncbi.nlm.nih.gov]
  • This case provides further evidence implicating CMV infection in the etiology of hypertensive iridocyclitis.[ncbi.nlm.nih.gov]
  • An extensive diagnostic workup was performed, including fluorescein angiography, serologic testing for infectious etiologies including syphilis and tuberculosis and a temporal artery biopsy.[ncbi.nlm.nih.gov]
  • These include CMV infecting the eye causing retinitis, Pneumonitis of unknown etiology (Probably CMV) and Pseudomonas aeruginosa infection in the UTI.[omicsonline.org]

Epidemiology

  • Division of Laboratory Medicine, University Hospital of Geneva and Medical School, University of Geneva, Geneva hDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.[ncbi.nlm.nih.gov]
  • PURPOSE: We report the epidemiologic trend of cytomegalovirus (CMV) retinitis among human immunodeficiency virus (HIV) patients in Singapore.[ncbi.nlm.nih.gov]
  • However, there is the lack of epidemiological report on the incidence of CMV retinitis in the AIDS patients in China.[bmcinfectdis.biomedcentral.com]
  • Kestelyn P (1999) The epidemiology of CMV in Africa. Ocul Immunol Inflamm 7: 173–177. View Article Google Scholar 16.[doi.org]
Sex distribution
Age distribution

Pathophysiology

  • Offers the most comprehensive content available on retina , balancing the latest scientific research and clinical correlations, covering everything you need to know on retinal diagnosis, treatment, development, structure, function, and pathophysiology[books.google.es]
  • Comprehensively updated to reflect everything you need to know regarding retinal diagnosis, treatment, development, structure, function, and pathophysiology, this monumental ophthalmology reference work equips you with expert answers to virtually any[books.google.es]
  • Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group, N Engl J Med, 2000 , vol. 343 (pg. 1594 - 602 ) 17 Anti-tumour necrosis factor specific antibody (infliximab) treatment provides insights into the pathophysiology[academic.oup.com]
  • Pathophysiology CMV reaches the retina hematogenously and infects the vascular endothelium which then spreads to the retinal cells. Impaired CD4 cell function permits uncontrolled CMV replication.[eyewiki.aao.org]
  • […] of CMV retinitis by allowing immune reconstitution in many individuals. [11, 12, 13] Over a period of 5 years, the incidence of opportunistic infections has decreased, and newly diagnosed cases of CMV retinitis have decreased by as much as 83%. [14] Pathophysiology[emedicine.com]

Prevention

  • Systematic screening of HIV patients with CD4 counts below 100 cells/μl should be carried out to detect disease at an early stage, when blindness can still be prevented.[ncbi.nlm.nih.gov]
  • Hence, early intervention may be crucial to prevent its progression to irreversible visual loss.[ncbi.nlm.nih.gov]
  • CMV retinitis causes debilitating, permanent sequelae, which is preventable by ART initiation at higher CD4 cell counts.[ncbi.nlm.nih.gov]
  • Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of[journals.sbmu.ac.ir]
  • This multicenter, prospective, observational study of patients with AIDS is identifying key combinations of drug treatments to prevent blinding eye disease in AIDS patients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .[medschool.lsuhsc.edu]

References

Article

  1. López-Contreras J, Ris J, Domingo P, Puig M, Rabella N, Nolla J. Disseminated cytomegalovirus infection in an immunocompetent adult successfully treated with ganciclovir. Scand J Infect Dis. 1995;27(5):523-525.
  2. Glasgow BJ, Weisberger AK. A quantitative and cartographic study of retinal microvasculopathy in acquired immunodeficiency syndrome. Am J Ophthalmol. 1994;118(1):46-56.
  3. Britt W. Manifestations of human cytomegalovirus infection: proposed mechanisms of acute and chronic disease. Curr Top Microbiol Immunol. 2008;325:417-470.
  4. Bhat V, Joshi A, Sarode R, Chavan P. Cytomegalovirus infection in the bone marrow transplant patient. World J Transplant. 2015;5(4):287–291.
  5. Vertes D, Snyers B, De Potter P. Cytomegalovirus retinitis after low-dose intravitreous triamcinolone acetonide in an immunocompetent patient: a warning for the widespread use of intravitreous corticosteroids. Int Ophthalmol. 2010;30(5):595-597.
  6. Kelkar A, Kelkar J, Kelkar S, Bhirud S, Biswas J. Cytomegalovirus retinitis in a seronegative patient with systemic lupus erythematosus on immunosuppressive therapy. J Ophthalmic Inflamm Infect. 2011;1(3):129–132.
  7. Wei LL, Park SS, Skiest DJ. Prevalence of visual symptoms among patients with newly diagnosed cytomegalovirus retinitis. Retina. 2002;22(3):278-282.
  8. Baumal CR, Levin AV, Kavalec CC, Petric M, Khan H, Read SE. Screening for CMV retinitis in children. Arch Pediatr Adolesc Med. 1996;150(11):1186-1192.
  9. Jabs DA. Ocular manifestations of HIV infection. Trans Am Ophthalmol Soc. 1995;93:623-683.
  10. Gupta S, Vemulakonda GA, Suhler EB, et al. Cytomegalovirus retinitis in the absence of AIDS. Can J Ophthalmol. 2013;48(2):126-129.
  11. Saidel MA, Berreen J, Margolis TP. Cytomegalovirus retinitis after intravitreous triamcinolone in an immunocompetent patient. Am J Ophthalmol. Am J Ophthalmol. 2005;140(6):1141-1143.

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Last updated: 2019-07-11 20:29