Progressive outer retinal necrosis: Dual virus involvement.

A 17-year-old male, newly diagnosed with human immunodeficiency virus (HIV) infection [on highly active antiretroviral therapy (HAART)], presented to our uveitis clinic with a 4-week history of gradual, painless loss of vision in the left eye (OS). He was being treated with oral valganciclovir and intravitreal ganciclovir injection elsewhere for presumptive diagnosis of cytomegalovirus (CMV) retinitis. General physical examination revealed multiple healed facial lesions on the left side of the face having a classical dermatomal distribution suggestive of a previous attack of Herpes Zoster dermatitis [Fig. 1a, black arrows]. His CD4+ T cell count was 61 cells/microliter. Ophthalmologic examination revealed visual acuity of hand motions in OS and 20/20 in OD. Fundus evaluation of OS showed minimal vitreous cells, retinitis with classic 'cracked mud' appearance [Fig. 1b]. The spectral-domain optical coherence tomography (OCT) showed the destruction of all retinal layers which appear as a single hyperreflective structure [Fig. 1c], yellow star], with hyporeflective areas at the level of outer retinal layers [Fig. 1c], yellow arrow]. The diagnosis was revised to progressive outer retinal necrosis (PORN).

Figure 1

Photograph of the patient showing multiple healed Herpes Zoster dermatitis lesions on left side of face. The scars have a classical dermatomal distribution (black arrows) (a); Wide angle fundus pictures of left eye at presentation showing multiple opaque yellowish-white lesions all over the fundus with sparing of the retinal vessels giving ‘cracked mud’ appearance (b); Optical coherence tomography image showing distorted architecture affecting all retinal layers which appears as a single hyper-reflective structure (yellow star), with optically empty spaces at the level of the outer nuclear layer (yellow arrow). Posterior hyaloid appears thickened with minimal vitritis (c)

Viral polymerase chain reaction (PCR) from vitreous fluid showed positivity for both CMV and varicella-zoster virus (VZV). Real-time PCR (RT-PCR) using the TaqMan probe was done on the vitreous sample [Fig. 2a and b]. The PCR kit used was in vitro diagnostic (IVD) approved CMV R-GENE® and HSV1&2 VZV R-GENE® (BioMérieux S.A, France) on RT- PCR system. The viral load as determined by PCR were 4 × 105 copies/ml for CMV and 5 × 104 copies/ml for VZV. Treatment was revised to weekly ganciclovir intravitreal injections (2 mg/0.05 ml) and oral valaciclovir (1 gm three times daily). A significant response was noted within 2 weeks after starting treatment [Fig. 3a], green arrows]. Five ganciclovir intravitreal injections (2 mg/0.05 ml) were given at weekly intervals. The patient was continued with oral valaciclovir (1 gm three times daily). He was lost to follow-up after 3 months. At the last follow-up, retinitis was healing significantly leaving behind extensively atrophic retina [Fig. 3b], black arrow], best corrected visual acuity (BCVA) was perception of light (PL+) with inaccurate projection of rays (PR). Retinal detachment was not seen. The right eye was normal. CD4 count had decreased to 55 cells/microliter.

Figure 2

The graph showing the amplification curve obtained from the real-time polymerase chain reaction (RT-PCR). The blue line corresponds to CMV whereas the orange one corresponds to VZV. An increase in fluorescence after multiple amplification cycles denotes the presence of the viral genes in the sample (a); The flat lines denote the control arm. 6-Carboxyfluorescein (FAM) dye was used to detect any fluorescent activity. The flat lines indicate the absence of significant fluorescent activity (b)

Figure 3

Wide-angle fundus photograph at 2 weeks follow-up showing atrophic retina due to healing of retinitis lesions (green arrows) and disc pallor (a). At 3 months follow-up, retinitis has healed significantly leaving behind extensive areas of atrophic retina (black arrow, b)

Discussion

PORN is a VZV retinopathy seen in severely immunocompromised patients usually in acquired immunodeficiency syndrome (AIDS) patients.[1] The lesions involve outer retinal layers in the early stage, progress quickly to involve all retinal layers.[2] There is minimal or no intraocular inflammation present. Perivascular sparing gives a typical 'cracked mud' appearance.[3] VZV is the main causative organism though Wong et al.[4] have reported both HSV and CMV being associated with PORN. We report a PCR proven case of PORN with dual viral positivity.

Patients with HIV are prone to multiple infections. Our patient was positive for both CMV and VZV proved by highly specific RT-PCR. The clinical picture was classical of PORN. After modification of treatment according to the PCR report, the patient responded well with the resolution of retinitis lesions.

Declaration of patient consent

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Conflicts of interest

There are no conflicts of interest.