Pachychoroid Associated With Acute Retinal Necrosis Secondary to Varicella Zoster Virus

Abstract

Purpose: To report a case of pachychoroid associated with acute retinal necrosis secondary to the varicella zoster virus (VZV). Methods: A retrospective review of a single case was performed. Results: The VZV-related acute retinal necrosis with pachychoroid resolved with quiescence of the acute infectious process. Conclusions: Acute retinal necrosis can result in choroidal thickening adjacent to retinitis. Previous reports have described choroidal sparing in these cases.

Introduction

Acute retinal necrosis (ARN) is a rare disorder, with an incidence of 0.63 cases per million population each year. ¹ The 2021 Standard Uveitis Nomenclature diagnostic criteria recently defined ARN as a peripheral necrotizing retinitis with either (1) confirmation via polymerase chain reaction (PCR) of intraocular infection with herpes simplex virus (HSV) or varicella zoster virus (VZV) or (2) the classic clinical picture (ie, confluent or circumferential retinitis, retinal vascular inflammation, and greater than minimal vitritis). ¹

Treatment includes antiviral therapy, usually oral and intravitreal, with local or systemic steroid therapy to reduce intraocular inflammation. The visual prognosis is guarded, with up to 85% of eyes developing retinal detachments (RDs) and approximately 50% of eyes with 20/200 or worse visual acuity (VA) 6 months after initial presentation.^1,2 Accurate and rapid diagnosis is critical to allow aggressive and urgent treatment, and multimodal imaging can be helpful in evaluating these cases. Optical coherence tomography (OCT) has been used to image areas of retinitis and shows full-thickness retinal hyperreflectivity and retinal thickening, vitritis, and subretinal fluid (SRF). OCT is thought to be helpful in distinguishing viral ARN from other nonviral causes of retinitis, such as toxoplasmosis, because ARN was thought to spare the choroid, whereas focal thickening of the choroid is highly suggestive of toxoplasmosis. ³

We performed a retrospective chart review of a patient with VZV-related, PCR-confirmed ARN that resulted in typical OCT characteristics of full-thickness retinal hyperreflectivity, vitritis, and SRF and also showed a new finding—choroidal thickening underlying the area of retinal involvement. Furthermore, the choroidal thickening resolved after treatment with antivirals and steroids. To our knowledge, pachychoroid caused by viral ARN has not been previously reported.

Case Report

A 47-year-old man presented reporting floaters, redness, and blurred vision in the right eye. His Snellen VA measured 20/30 (pinhole to 20/25) OD and 20/20 OS. The intraocular pressure was 21 mm Hg and 16 mm Hg, respectively.

An anterior segment examination of the right eye was notable for 1+ conjunctival injection with mild inferior punctate keratic precipitates and 3+ anterior chamber cells. The left anterior segment was unremarkable. A posterior segment examination of the right eye was notable for 2+ vitreous cells, mild engorgement of the retinal vessels with vascular sheathing, peripheral intraretinal hemorrhages, dense inferior peripheral retinal whitening, and scattered peripheral small white satellite lesions throughout the periphery (Figure 1). The posterior segment in the left eye was unremarkable.

Figure 1.

Widefield fundus photograph of the right eye shows multifocal areas of retinitis and intraretinal hemorrhage as well as peripheral arteriolitis.

Macular OCT of the right eye showed a mild epiretinal membrane, hyperreflective vitreous debris, and a normal choroidal thickness symmetric with the other eye. Extramacular scans directed over the inferior near periphery in an area of retinitis showed hyperreflectivity of the retina, SRF, and considerable pachychoroid (Figure 2). Areas adjacent to the retinitis had normal choroidal thickness. Fluorescein angiography of the right eye showed a normal filling pattern with arteriolar sheathing nasally, inferior blocking at areas of retinitis and hemorrhage, and late diffuse vascular leakage (Figure 3).

Figure 2.

Extramacular optical coherence tomography directed over a segment of retinitis showing vitreous opacities, retinal thickening and hyperreflectivity, subretinal fluid, and pachychoroid.

Figure 3.

Widefield intravenous fluorescein angiography at 1 minute 37 seconds shows choroidal hyperfluorescence, arteriolar leakage nasally, inferior blocking at areas of retinitis and hemorrhage, and diffuse vascular leakage.

The clinical presentation was suspicious for viral retinitis. Initial laboratory work included a complete blood count, syphilis antibodies, HIV antibodies, and QuantiFERON gold. An anterior chamber paracentesis with PCR testing for HSV, VZV, and cytomegalovirus was performed. At presentation, given the high clinical suspicion for a viral retinitis, the patient was started on 2 g of oral valacyclovir 3 times daily. Initial PCR results were negative. Syphilis, HIV, and tuberculosis testing were negative, and a complete blood count was unremarkable.

Three days after the patient’s initial presentation, worsening arteriolitis was noted on examination. Oral prednisone 60 mg per day and topical prednisolone acetate 1% 4 times a day were started. Clinical suspicion for ARN was still high despite the initial negative PCR testing. Five days after initial presentation, the arteriolitis continued to worsen. Thus, the patient was given an intravitreal injection of ganciclovir 2 mg/0.1 mL and a second PCR from aqueous humor was sent. The second PCR test detected VZV, confirming the diagnosis.

The patient continued on valacyclovir, oral prednisone, and prednisolone and subsequently received 3 more ganciclovir injections over the next 2 weeks. His clinical examination gradually improved. One month after presentation, the valacyclovir was decreased to 1 g 3 times a day. Prophylactic laser retinopexy was performed to decrease the chance of rhegmatogenous RD. At the time of writing, the patient was stable on a continued oral and topical steroid taper.

Extramacular OCT scans over previous areas of retinitis taken 3 months after initial presentation showed full-thickness retinal tissue loss, resolution of the SRF, and a reduction in pachychoroid (Figure 4).

Figure 4.

Extramacular optical coherence tomography 3 months after presentation directed over the segment of retinitis in Figure 2. There is a decrease in vitreous opacities and resolution of retinal hyperreflectivity, subretinal fluid, and pachychoroid. Note the full-thickness retinal necrosis at the previous retinitis site. Laser scars can be seen bordering the necrotic retina.

Conclusions

To our knowledge, this is the first reported case of the presence of pachychoroid in the setting of PCR-confirmed viral ARN. Previously, the presence of pachychoroid could erroneously lead providers toward the diagnosis of toxoplasmosis or other pathologies that preferentially involve the choroid with subsequent retinal involvement, including fungal or bacterial infections. ³ Typically, the clinical context and fundoscopic appearance can differentiate these etiologies. In cases of immunosuppression or atypical presentations, OCT findings are helpful in establishing the diagnosis. Thus, including viral ARN as a differential diagnosis when confronted with retinitis associated with pachychoroid is important for proper diagnosis and management.

A few potential mechanisms could explain the pachychoroid found in viral ARN. There is a possibility of direct viral infection of the choroid; however, we suspect this is less likely given the absence of late choroidal destruction on OCT in this case. Likewise, the absence of choroidal nonperfusion in areas of thickening, as might be expected with destruction of the choriocapillaris secondary to viral infiltration, makes direct viral choroid involvement less likely. We suspect the choroidal thickening was more likely secondary to local inflammation or ischemia given that numerous cytokine mediators have been described in ARN and could lead to a local inflammatory response in the underlying choroid.^4–8 Therefore, we are describing this choroidal thickening as reactive and secondary to the primary retinal pathology. Although this appears to be a novel case, recent improvements in OCT could explain why similar choroidal alterations in this setting have not been previously documented in the literature. ⁹ With awareness of this finding, detection of future cases may become more common.

Stuebiger et al ¹⁰ described a case of central serous chorioretinopathy (CSCR) with SRF after ARN that the authors attributed to systemic steroid therapy. In our patient’s case, pachychoroid was present before topical or systemic steroid use, removing CSCR as a diagnostic consideration. Pachychoroid has also been described in cases of systemic viral infection (Table 1).^10–13 It is unclear whether the mechanism in these systemic cases is the same as in our patient’s case or whether the pachychoroid was caused by an increase in systemic cortisol, which is more resembling of typical CSCR.

Table 1.

Cases of Viral Infection With Pachychoroid Manifestations.

Authors	Study Design	Clinical Features
Stuebiger et al10	Case report	CSCR developed after ARN resolved with steroid treatment in an immunocompetent patient.
Yudhishdran et al11	Case report	Foveolitis in the right eye and CSCR in the left eye in a patient with dengue fever.
Tesař et al12	Case report	Choroidal thickening with subretinal fluid in a patient with recent coxsackievirus infection.
Abrishami et al13	Case series	Four patients demonstrated pachychoroid and pachyvessels with choroidal hyperpermeability after COVID-19 infection.

Abbreviations: ARN, acute retinal necrosis; CSCR, central serous chorioretinopathy.

In conclusion, pachychoroid is a possible OCT finding in the acute phase of ARN and does not eliminate viral etiologies as a potential cause of the retinitis. The pachychoroid in our patient’s case resolved with quiescence of the active infection and may be useful as an additional imaging marker of active disease. This case of reactive choroidal thickening related to viral ARN is an important addition to the literature because it builds on the spectrum of OCT findings in cases of viral ARN. Likewise, this addition expands the differential in ambiguous cases of pachychoroid where toxoplasmosis and other etiologies are classically considered.