CMVR – Awareness is Better Than Ignorance

Tathagata Roy, B.Optom

Fellow Optometrist, Vitreo-retina Department, Dr. Shroff’s Charity Eye Hospital, New Delhi, India

 

Viral ocular infection caused by herpes although very common yet one of the most serious complications leading to irreversible vision loss.⁽¹⁾ Cytomegalovirus retinitis is seen in patients immunocompromised from a variety of causes; it is a common opportunistic ocular infection in patients with AIDS, in whom it may represent reactivation of a latent infection. Untreated Cytomegalovirus retinitis is persistently progressive and will ruin the vascular endothelial cells followed by the retinal pigment epithelial cells within 4-6 months.^(1,4) Clusters of differentiation 4 (CD 4) count less than 100 cells/µL HIV patients who have visual symptoms are at high risk of Cytomegalovirus retinopathy (CMVR).

Figure 1: Colour fundus photo shows the superior arcades with retinal whitening and haemorrhage.

Mostly, peripheral CMVR patients may be asymptomatic but if symptomatic then the patient may complain of floaters, scotomata or peripheral visual field defects associating central retinal lesions. Lack of awareness of this condition provides a route to visual impairment and is termed as ‘the neglected disease of the AIDS pandemic’. Systematic detection of cases of early CMVR involvement will increase the chances of treatment to maintain visual acuity and be applied to patients prior to Highly active antiretroviral therapy (HAART), it stops the virus to produce replica of itself in the body,  who are at risk of mediated ocular immune – reconstitution. Reported rates CMVR effects from 27-33% of HIV – infected individuals. In the Indian sub-continent 9-17% are affected. ⁽²⁾

Figure 2: OCT reveals severe retinal architectural disruption and obliteration of the ellipsoid zone (EZ) and external limiting membrane (ELM) (or thickening and irregularity of the EZ, absence of ELM)

The large genome of CMV virus rapidly migrates into the nucleus of infected cells and initiates the production of viral progeny in the lytic life cycle. The progeny viruses then leave the infected cell to infect neighbouring cells and repeat the process. Uncontrolled viral replication causes cell death in the affected retinal tissue, leading to blurred vision, retinal detachment and ultimately blindness.

CMVR in non – HIV cases have been observed in patients undergoing immunosuppressive therapies for hematologic malignancies, autoimmune disease, bone marrow and solid organ transplantation, and after local steroid administration.

Fluorescent angiographic (FA) features of CMVR may include disc leaks and areas of active retinitis, blocking defects in hemorrhagic areas. FA can identify late complications of CMVR including papillary neovascularisation, choroidal neovascularisation, and cystoid macular oedema (CME). ⁽³⁾

Fundus autofluorescence (FAF) can be useful in detecting the early development of CMVR. In active retinitis, the progressive edges of the lesion become hyper – auto fluorescent, which helps the clinician see subtle areas of progression or reactivation.⁽³⁾

In CMVR cases spectral domain optical coherence tomography (SD – OCT) is not much significant. Monitoring the border between normal and abnormal ellipsoid areas is an important consideration with SD – OCT, which is assessed to detect microstructural development. ^(2,3)

Polymerase chain reaction analysis of aqueous or vitreous ocular fluid can further confirm the diagnosis and may be useful in the presence of atypical clinical symptoms, helps to differentiate CMVR from other retinitis caused by other members of the Herpesvirus family, such as varicella Zoster or herpes simplex virus or from other pathogens such as Toxoplasma gondii. ⁽³⁾

In case of management, HAART is the mainstay of management, restoring the patient’s innate ability to suppress CMV activity. Discontinuation of antiviral treatment is considered when the CD4⁺ count reaches more than 100 – 150 cells/ µL. ^(1,5)

Valganciclovir is taken orally (900 mg twice daily for up to 3 weeks) and effective for both induction and maintenance, where Ganciclovir, foscarnet and cidofovir given intravenously were formerly key therapeutic agents.^(1,5)

Vitrectomy with Endo laser demarcation and silicone oil tamponade is successful in around 75% of CMV related retinal detachments (RDs). ⁽¹⁾

Screening will be a good option for HIV patients for detection & early accessible treatment for CMV retinitis.

 

References:

1. Mannis MJ. Kanski’s clinical ophthalmology: A systematic approach.
2. Ho M, Invernizzi A, Zagora S, et al. Presenting Features, Treatment and Clinical Outcomes of Cytomegalovirus Retinitis: Non-HIV Patients Vs HIV Patients. OcularImmunology and Inflammation. 2019; 29:535-542.
3. Vrabec TR, Baldassano VF, Whitcup SM. Discontinuation of maintenance therapy in patients with quiescent cytomegalovirus retinitis and elevated CD4+ counts. Ophthalmology. 1998 Jul 1;105(7):1259-64.
4. Munro M, Yadavalli T, Fonteh C, Arfeen S, Lobo-Chan AM. Cytomegalovirus retinitis in HIV and non-HIV individuals. Microorganisms. 2019 Dec 28;8(1):55.
5. Vadlapudi A.D., Vadlapatla R.K., Mitra A.K. Current and emerging antivirals for the treatment of cytomegalovirus (CMV) retinitis: An update on recent patents. Recent Pat. Anti-Infect. Drug Discov. 2012; 7:8–18. doi: 10.2174/157489112799829765.

Sources of figure: Author has captured the retinal scans used in this blog.