A Novel Approach for RD in Viral Retinitis

The PFO-foscarnet pocket is an option for treating a detached retina in this difficult clinical setting.

David R.P. Almeida, MD, MBA, PhD, and Eric K. Chin, MD
By
First described as acute retinal necrosis by Akira Urayama, MD, and colleagues at Tohoku University in Japan in 1971,1 viral retinitis typically manifests as a progressive occlusive necrotizing vasculitis involving retinal and choroidal vasculature with subsequent retinal detachment.2,3 Bilateral viral retinitis, also known as bilateral ARN (BARN), occurs in up to a third of cases.3,4
 

Viral retinitis is rare—0.63 cases per 1 million population per year—with equal incidence among males and females and a large variation in age of presentation.5,6 However, mixed-mechanism retinal detachment secondary to viral retinitis is common, occurring in 20 to 75 percent of these eyes, with resultant poor visual outcomes.7-10 These complex RDs require surgery. Here, we discuss our own study of surgical and anatomic outcomes in patients with RD secondary to viral retinitis11 and highlight a novel surgical technique called the “PFO-foscarnet pocket.”12

Etiology of Viral Retinitis

Diagnosis of viral retinitis is based on the American Uveitis Society clinical criteria that include:

Focal, well-demarcated areas of retinal necrosis in the peripheral retina.

Rapid and circumferential progression of necrosis.

Evidence of occlusive vasculopathy.

Prominent inflammatory reaction in the vitreous and anterior chamber.13

Etiology in immunocompetent patients is varicella zoster virus in 50 percent, herpes simplex virus in 25 percent, Epstein-Barr virus in 15 percent and cytomegalovirus (CMV) in 1 percent, although the latter is much more common in immunocompromised patients.14–16

 
Polymerase chain reaction analysis of aqueous and vitreous samples is the gold standard for diagnosis, with a sensitivity of 95 percent and specificity of 97 percent,17-19 and for monitoring disease course and response to therapy via viral load quantification.20-22 Treatment standards currently call for oral medications such as acyclovir (800 mg five times per day),23 valacyclovir (1 g t.i.d.)24 or famciclovir (500 mg t.i.d.).25 They seem to have similar efficacy to the traditional intravenous acyclovir (1,500 mg/m2 body surface area) regimen.26

Oral agents like valacyclovir and famciclovir have superior bioavailability and central nervous system penetration compared to acyclovir and seem to have utility in both the initial treatment and maintenance therapy of patients with viral retinitis.3 A six-to-eight-week induction period followed by a three-to-six-month maintenance phase seems to be effective in this often chronic and recurrent clinical course.
 


RDs in Viral Retinitis

RDs in viral retinitis usually occur after the acute phase of infection and are secondary to vitreous traction on the necrotic retina and inflammatory membranes, resulting in stretch holes and a partially rhegmatogenous component.27

In our study, all cases underwent three-port pars plana vitrectomy (PPV) with induction of a posterior vitreous detachment, if not already present. We employed membrane peeling, retinotomies and retinectomies to remove inflammatory vitreal and retinal membranes as well as necrotic retina (video available at bit.ly/2eKmGzW), and performed tamponade with 1,000-centistoke silicone oil in 11 of 12 eyes. During PPV, we placed a scleral buckle in 10 eyes (83.3 percent).

Initial surgery achieved successful anatomic re-attachment of the retina in all cases, and no re-detachments occurred during the follow-up period. In 50 percent of eyes, we successfully removed silicone oil at a later date with no recurrence of retinal detachment during the study period.

Foscarnet During Surgery

To view a video that demonstrates the technique Drs. Almeida and Chin discuss, click here.
Although oral valacyclovir penetrates intraocular tissue, we know that direct intravitreal antiviral therapy may be more effective. Delivering intravitreal therapies in the setting of silicone oil tamponade is challenging. One must use caution because delayed clearance of intravitreal antivirals from silicone oil-filled eyes may result in retinal toxicity.

Unlike acyclovir or gancyclovir, antiviral foscarnet does not require thymidine kinase activation, so resistance is uncommon. Foscarnet selectively inhibits viral polymerase and can rapidly inactivate the virus with a short contact exposure time. Consequently, we have successfully incorporated this therapy at the time of surgical repair.12 The steps in the technique are:

Multiplane chromovitrectomy. This step facilitates retinal detachment repair with concurrent intraoperative intravitreal antiviral therapy prior to silicone oil tamponade.

After removal of all vitreous and necrotic retina, injection of perfluoro-n-octane (PFO) liquid over the posterior pole. This flattens any posteriorly detached retina up to the most posterior edge of any breaks, creating a PFO-infusion fluid meniscus. At this point, there are two distinct phases in the vitreous cavity: a PFO bubble over the posterior pole; and a layer of balanced salt solution (BSS) more anteriorly. The PFO flattens and immobilizes the retina more posteriorly in its usual manner.

Injection of approximately 0.1 to 0.2 mL of foscarnet (2.4 mg per 0.1 mL) over the PFO into the BSS more anteriorly. This creates a PFO-foscarnet “pocket” or “shell” that allows the foscarnet to penetrate the retina while the PFO stabilizes the posterior retina.

At this point, laser retinopexy or any additional vitrectomy or retinectomy can be performed. If needed, this will allow the intravitreal foscarnet to have increased exposure time to the diseased peripheral retina.

Air-fluid exchange. Upon completion of the vitrectomy, a soft-tipped extrusion cannula helps to perform an air-fluid exchange by first removing the anterior BSS-foscarnet followed by the more posterior PFO.

Foscarnet wash. In the final step, injection of three to five drops of foscarnet over the posterior pole in the air-filled eye performs a foscarnet wash. This allows the foscarnet to penetrate any posterior retina previously inaccessible owing to the PFO placement. The silicone-tip extrusion needle helps to remove the foscarnet and any remaining BSS. The technique allows stabilization of the detached retina while allowing for antiviral washout during vitrectomy.
 


We identified optic nerve involvement as a poor prognostic factor because only eyes without optic nerve involvement were able to achieve visual acuity of 20/100 or better. We used the proposed absolute criteria for optic nerve involvement in ARN to determine optic nerve involvement according to three criteria:

Afferent papillary defect not consistent with the retinal findings.

Poor correlation between retinal findings and visual acuity.

Sudden deterioration of visual acuity to 20/100 or worse without corresponding retinal changes within a 24- to 36-hour interval.28

Visual acuity seems unlikely to improve in these cases. Subsequent interventions primarily aim to prevent involvement of the fellow eye, chronic retinal detachment and phthisis bulbi.

Our novel PFO-foscarnet pocket allows for intraoperative antiviral coverage in this challenging group of patients, who often require long-acting silicone oil tamponade.  RS

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