Retina Associates’ Case of the Month: September 2016

Fig 1 Large

Author: Samantha Fraser-Bell

Figure 1. The left fundus shows a patch of acute retinal necrosis affecting the left macula. There are 2 cotton wool spots visible in the right fundus photograph.

Figure 1.
The left fundus shows a patch of acute retinal necrosis affecting the left macula. There are 2 cotton wool spots visible in the right fundus photograph.

A 56-year-old man presented with a 2 day history of reduced left vision

Case History

A 56-year-old man presented complaining of acute loss of left vision the previous day. He had a history of T cell lymphoma with secondary haemophagocytic syndrome and was on high dose dexamethasone and etoposide. Systemically he was febrile with a low neutrophil count (neutropaenic).

On examination, his right vision was 6/6 and left vision 6/60. There were no cells in either anterior chamber. Intraocular pressures were 15mmHg each eye. There was mild left vitritis. Dilated examination of the right fundus revealed an occasional cotton wool spot. Examination of the left fundus is shown in Figure 1. There is evidence of retinitis with haemorrhage affecting the macula.

 

What is your diagnosis?

Differential diagnosis

The causes of acute retinal necrosis (ARN) in an immunocompromised patient include:

  • Cytomegalovirus (CMV)
  • Varicella zoster virus (VZV)
  • Herpes simplex virus (HSV)
  • Toxoplasmosis
  • Blood borne infections/endogenous endophthalmitis

The cotton wool spots in the fellow eye are most likely due to the patient’s concurrent anaemia.

Initial treatment
  • A sample of vitreous was taken using a 23gauge needle and an intravitreal injection of foscarnet was given (2.4mg/0.1ml). Foscarnet was chosen as it is a broad spectrum antiviral which is generally effective for CMV, HSV and VZV which are the most common causes of retinitis. Also, these herpetic viruses generally have the worst prognosis with delayed treatment.
  • Ganciclovir was started intravenously as this is the treatment of choice for CMV retinitis, which was the mostly likely organism.
Diagnosis
  • The vitreous biopsy was positive for CMV using PCR testing.
  • Despite intravitreal and systemic treatment, the lesion initially increased in size and 2 further foscarnet injections every third day were given (Figure 2) before stability was achieved. After induction therapy with intravenous ganciclovir, the oral form (valganciclovir) was used.
Figure 2. Initially the area of retinal necrosis increased.

Figure 2.
Initially the area of retinal necrosis increased.

 

Clinical course

The patient remained systemically unwell due to his coexistent lymphoma and unfortunately, he passed away within 3 months of this presentation.

Discussion

CMV is a double stranded DNA Herpes virus. CMV is ubiquitous but is an opportunistic infection affecting patients who are immunocompromised. CMV retinitis is most commonly associated with patients with HIV and a CD4 count less than 50. Treatment for HIV normally increases the CD4 count whereby a patient’s own immunity can keep ocular CMV in remission. Because CMV can affect patients systemically, including colitis, pneumonitis and encephalitis, patients who are immunosuppressed post solid organ transplants often take medication for CMV prophylaxis. As with this patient, CMV retinitis can also occur in patients with lymphoma and also in patients with autoimmune disorders on high dose corticosteroids or on steroid-sparing immunosuppressive agents.

Ophthalmic features include retinitis in one or both eyes. Associated haemorrhage is common. Most commonly retinitis starts in the peripheral retina, but as in this case, it may present in the macular region. Vitritis is typically mild or absent but there may be associated vasculitis or a “frosted branch’’ appearance. It can also present as a granular retinitis which can be subtle.

Complications include retinal detachment especially for peripheral lesions. Systemic therapy is essential to prevent fellow eye involvement and extraocular infection.

First line treatment is induction with intravitreal foscarnet and/or intravitreal ganciclovir and intravenous ganciclovir 5mg/kg bd for 2 weeks followed by oral valganciclovir. Side effects include bone marrow suppression and neutropenia.

Take home points
  • Patients with retinitis are at risk of severe vision loss and need urgent ocular treatment.
  • Patients with retinitis are often systemically unwell.
  • Patients with retinitis due to CMV are also systemically infected with CMV and are at risk of colitis, pneumonitis and encephalitis and require systemic treatment to treat this as well as their retinitis.

 

References
  • Cvetković RS, Wellington K. Valganciclovir: a review of its use in the management of CMV infection and disease in immunocompromised patients. Drugs. 2005;65:859-78.
  • Jabs DA et al. Comparison of Treatment Regimens for Cytomegalovirus Retinitis in Patients with AIDS in the Era of Highly Active Antiretroviral Therapy. Ophthalmology, 2013;120:1262-70
  • Jabs DA, Martin BK, Forman MS, et al, Cytomegalovirus Retinitis and Viral Resistance Research Group. Cytomegalovirus resistance to ganciclovir and clinical outcomes of patient with cytomegalovirus retinitis. Am J Ophthalmol 2003;135:26 –34
  • Stewart, M. Optimal Management of CMV retinitis in patients with AIDS. Clin Ophthalmol. 2010; 4:285-99