H₁N₁-associated Acute Retinitis

Abstract

Purpose: To present the first reported case of bilateral H₁N₁-associated acute retinitis and its successful treatment.

Design: Interventional case report.

Methods: A 41-year-old HIV-positive male presented with acute vision loss, panuveitis, and retinitis. A diagnostic and therapeutic vitrectomy with intravitreal injection of vancomycin and ganciclovir and endolaser was performed. One month later, the patient returned with similar symptoms in the fellow eye and underwent the same procedure.

Results: ELISA immunoassay revealed H₁N₁ antibodies in both the vitreous and serum. PCR for herpes viruses included HSV, CMV, and VZV. Bacterial and fungal cultures were negative. On 1-year follow-up, the vision remained 20/20 in both eyes without evidence of recurrent inflammation.

Conclusions: H₁N₁ should be included in the differential diagnosis of any patient with a history of recent influenza A (H₁N₁) infection and acute retinitis. H₁N₁ may carry a better prognosis than other viruses causing acute retinitis.

Keywords:

• H₁N₁
• retinitis
• viral
• influenza A
• vitrectomy
• intravitreal biopsy
• intravitreal antibiotics

Viral retinitis is one of the most common causes of infection involving the posterior segment and is a potentially visually devastating disease affecting both immunocompetent and immunocompromised individuals.¹ Viral retinitis may be congenital or acquired, most commonly due to cytomegalovirus.² Ocular involvement in cytomegalovirus has been reported to be between 12 and 46% of patients with acquired immune deficiency syndrome (AIDS).³ Other documented causes of ophthalmic manifestations of systemic viral disease include herpes zoster, herpes simplex, and Epstein-Barr virus.⁴ Influenza A has also been implicated in few reports of ocular findings in systemically infected individuals, with potential findings of influenza A retinopathy, macular edema, foveal irregularity,⁵ and optic neuritis.⁶

H₁N₁ (avian influenza A, swine flu) hit the United States in April 2009, when a 10-year-old patient in California was diagnosed with a influenza strain variant.⁷ Patients infected with H₁N₁ may present with flu symptoms such as fever, cough, and body aches. Eye involvement has rarely been reported—limited to one case of presumed H₁N₁ retinopathy⁸ and a report of a child who developed bilateral acute anterior uveitis, papillitis, and neuroretinitis after a respiratory infection of H₁N₁.⁹ Treatment of influenza caused by H₁N₁ has proven difficult as resistance is quite high. According to the Centers of Disease Control (CDC), in 2007, resistance to the commonly used anti-virals amantadine and rimantadine was nearly 100%. In 2009, resistance to oseltamavir was noted to also be near 100%.¹⁰

The aim of this case report is to present a patient with bilateral acute retinitis, likely secondary to H₁N₁, who was successfully treated with vitrectomy and intravitreal injection of vancomycin and ganciclovir.

CASE REPORT

A 41-year-old HIV-positive male suffered from redness, pain, and progressive decreased vision in his right eye for several days. Medical history was significant for a CD₄ count of 560, undetectable viral load, and recent H₁N₁ influenza, documented and confirmed by his primary care physician with a rapid influenza diagnostic test, and treated with systemic oseltamivir approximately 3 weeks prior to presentation to our service. Patient's visual acuity was 20/125 in the right eye and 20/20 in the left eye. The right eye demonstrated considerable conjunctival injection and chemosis. The anterior chamber revealed dense inflammation, hypopyon, fibrin, and posterior synechiae. Funduscopic examination revealed a dense vitritis and necrosis of the peripheral retina in the right eye (Figure 1A). The left eye was unremarkable.

Diagnostic as well as therapeutic pars plana vitrectomy surgery was performed on the right eye with an intravitreal injection of 1 mg/0.1 mL vancomycin, and 2 mg/0.1 mL ganciclovir. Prophylactic endolaser was also performed surrounding the retinitis, as demonstrated in the intraoperative video (which can be found in the online edition of this article). A vitreous biopsy revealed negative herpes viruses (HSV, VZV, and CMV) PCR acid-fast bacilli, and bacterial and fungal cultures. The patient was also prescribed 1 g of oral valacyclovir 3 times per day by the vitreoretinal surgeon.

FIGURE 1  (A) Mosaic color fundus photograph of the right eye, demonstrating focal and confluent areas of necrosis of the peripheral retina. Preretinal exudate, a “pseudohypopyon,” is also shown in addition to areas of retinal necrosis (arrow). (B) Mosaic color fundus photograph of the right eye after pars plana vitrectomy and laser retinopexy treatment, showing resolved retinal necrosis.

One week postoperatively, the vision in the right eye improved to 20/30 and pain had resolved. However, within 2 weeks the patient returned for a follow-up visit complaining of swelling, pain, and floaters in his fellow eye. Vision was 20/20 in both eyes. Examination of the anterior chamber revealed mild conjunctival infection and moderate inflammation in the left eye. Funduscopic examination demonstrated focal coalescent necrosis of the retina and vitreous haze, indicating retinitis in the fellow eye. The right eye remained stable.

The patient underwent a 25-gauge pars plana vitrectomy surgery in the left eye and intravitreal injection of the same doses of antibiotics and antiviral agents. One week postoperatively, the patient's vision was 20/20 in both eyes and retinal necrosis was completely resolved (Figure 1B). Vitreous herpes viruses (HSV, VZV, and CMV) PCR acid-fast bacilli, and bacterial and fungal cultures were negative. However, serum and vitreous ELISA immunoassay for influenza A (H₁N₁) antibodies were positive. At a 1-year follow-up examination, vision remained 20/20 in both eyes without evidence of recurrent intraocular inflammation. The patient is currently continuing his HIV medications only, as prescribed by his internist.

Although another herpetic viral cause of our patient is certainly high on the differential in this HIV-positive individual, our patient's rapid response to intravitreal anti-viral therapy, despite a negative viral workup, alludes to a viral cause, specifically H₁N₁, of his acute retinitis. The patient was on systemic valacyclovir when he developed contralateral retinitis, suggesting H₁N₁ rather than another virus as a cause for the retinitis. It is our belief that our patient, who suffered from viral retinitis, traditionally a devastating and blinding disease, had a favorable outcome due to several factors. Firstly, the patient sought treatment immediately upon experiencing visual symptoms. Secondly, his general ophthalmologist had a high index of suspicion for an infectious endophthalmitis and referred him immediately to a retina specialist. The patient was taken to surgery for a vitreous biopsy and intravitreal injection of broad-spectrum antibacterial and antiviral agents on the same day of consultation, without delay. Because of the acute nature of the retinitis and our suspicion of possible acute retinal necrosis (ARN), early surgery was recommended, yielding an excellent clinical result, despite the grim natural history of ARN. We cannot determine of this favorable prognosis was due to our early surgical intervention or because of the atypical viral cause. However, as small-gauge vitrectomy is available, the threshold for surgical intervention may be lower nowadays than in previous years.

It is plausible that this may be a case of retinitis secondary to a herpesvirus infection, undetected by PCR, although, the sensitivity and specificity of immunodetection of herpesvirus antigens are known to be over 90%.¹¹ The swine influenza virus (SIV) ELISA immunoassay (IDEXX Laboratories, Westbrook, Maine) that was used for the detection of antibodies to swine influenza virus in the serum and in the vitreous has limitations: although highly specific for the detection of H₁N₁ in serum, cross-reactivity has occurred in porcine serum and plasma to other SIV subtypes. The Goldmann Witmer coefficient was also calculated as (anti-SIV IgG in vitreous/total IgG in vitreous)/(anti-SIV IgG in serum/total IgG in serum) and found to be 2.8. A value of 2 was considered evidence of intraocular antibody synthesis.¹² However, sensitivities and specificities of the test to detect H₁N₁ antibodies in vitreous are currently unknown. Recently, reactivation of acute retinal necrosis from varicella zoster infection after H₁N₁ vaccination was reported.¹³ To our knowledge this is the first case to describe H₁N₁-associated acute retinitis, which may be caused by the H₁N₁ virus itself or be indicative of a secondary viral cause of acute retinitis undetected by PCR. Because antibodies and not antigens were identified, cross-reactivity to other viral antigens may be a confounding factor.

In summary, we highly recommend that any patient who has a history of recent influenza A (H₁N₁) infection and visual symptoms be referred immediately to an ophthalmologist. H₁N₁ may carry a better prognosis than other viruses causing acute retinitis. Without more reported cases, the favorable outcome of H₁N₁ retinitis as observed by our patient, may, in fact, be due to the natural history of progression of H₁N₁ retinitis and not a specific treatment.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.