Ocular Immunology and Inflammation

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ioii20

Detection of Pre-clinical Involvement of the

Second Eye in Viral Acute Retinal Necrosis Using
Optical Coherence Tomography

S Pockar , NP Jones , R Chhabra & LR Steeples

To cite this article: S Pockar , NP Jones , R Chhabra & LR Steeples (2020): Detection of Pre-
clinical Involvement of the Second Eye in Viral Acute Retinal Necrosis Using Optical Coherence
Tomography, Ocular Immunology and Inflammation, DOI: 10.1080/09273948.2020.1783324

To link to this article: https://doi.org/10.1080/09273948.2020.1783324

Published online: 20 Aug 2020.

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OCULAR IMMUNOLOGY AND INFLAMMATION
https://doi.org/10.1080/09273948.2020.1783324

LETTER TO THE EDITOR

Detection of Pre-clinical Involvement of the Second Eye in Viral Acute Retinal Necrosis
Using Optical Coherence Tomography
S Pockar MDa, NP Jones BSc, MBChB, DO, FRCSEd, FRCOphtha,b, R Chhabra MBBS, FRCS, DO, MSa,b,
and LR Steeples MBChB (Hons), FRCOphtha,b
a
Manchester Royal Eye Hospital, Medical Academic Health Science Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, UK;
b
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

ABSTRACT KEYWORDS
Purpose: To report the detection of retinitis in the second eye of a patient with viral acute retinal necrosis Acute retinal necrosis; optical
(ARN), before the appearance of clinical change, using swept-source optical coherence tomography. coherence tomography;
Results: A 63 year-old male developed right-sided varicella-zoster virus (VZV) ARN, confirmed with varicella zoster retinitis
aqueous sampling. High-dose intravenous aciclovir caused renal impairment and was suspended for
two-days. One day later, left eye macular SS-OCT revealed focal retinal thickening and disruption of retinal
architecture without clinically detectable retinitis. The patient was asymptomatic. Aqueous sampling was
VZV PCR positive. He received bilateral foscarnet injections and renal adjusted dose of aciclovir. The left
OCT signs improved with full restoration of retinal layers.
Conclusions: We report for the first time the use of OCT to detect pre-clinical second eye retinitis during
ARN. Prompt diagnosis and combined systemic and intensive local antiviral therapy resulted in a favour­
able structural and functional outcome.

Viral acute retinal necrosis (ARN) is a severe, rapidly progres­
sive, and sight-threatening infection. Visual outcomes are
usually poor. Typically unilateral at presentation, ARN
becomes bilateral in a significant proportion of cases without
treatment. Prompt diagnosis and systemic treatment are cru­
cial to limit visual loss and to prevent fellow eye involvement.
Method
We present a case of ARN and demonstrate swept-source
optical coherence tomography (SS-OCT) detection of second
eye retinal involvement before the appearance of symptoms or
clinically detectable change. Tomographic signs in the acute
phase and evolution during systemic and local antiviral therapy
are described.
Results
A 63 year-old male was referred to the Manchester Uveitis
Clinic (MUC) with a 2-week history of right reduced visual
acuity (VA) and panuveitis with severe retinal necrosis invol­
ving all four quadrants and zones 1–3 with occlusive arteritis.
Intravenous aciclovir (13 mg/kg TID) had been started 2 days
earlier and barrier laser retinopexy had been performed by the
referring center.
Visual acuity was hand movements right and 0.0 logMar left.
The left clinical examination and wide-field retinal imaging
including autofluorescence (Optos®) and OCT (SS-OCT;
Triton®, Topcon), was normal. Right aqueous sampling was
varicella-zoster virus (VZV) polymerase chain reaction (PCR)
positive. Intravitreal foscarnet (2.4 mg/0.1 ml) was injected.
Severe acute kidney injury was evident at presentation to MUC
(creatinine 395 µmol/L, eGFR 15 ml/min). Intravenous aciclovir
was suspended for 2 days and subsequently resumed at renal-
adjusted dose and supplemented by intravitreal foscarnet to the
right eye (twice weekly, total five injections). Immunodeficiency
investigations were negative.
Three days after stopping aciclovir, left low-grade vitritis was
observed but there was no clinically detectable retinitis and VA
was unchanged. Left macular OCT demonstrated a focal area of
retinal thickening nasal to the fovea with a band of inner-retinal
hyper-reflectivity, and disruption of structures from the outer
nuclear layer (ONL) to the ellipsoid zone (EZ) (Figure 1a).
Further focal areas of outer retinal hyper-reflectivities and disrup­
tion of the external limiting membrane (ELM), EZ and inter-
digitation zone (IZ) were observed at the fovea (Figure 1a).
Fundus autofluorescence and near infra-red imaging were normal.
Left intravitreal foscarnet (2.4 mg/0.1 ml) was administered on the
same day and aqueous was confirmed VZV positive. Intravenous
aciclovir was continued for 12 days, followed by oral valaciclovir
(2 gm TID). Renal function rapidly improved (eGFR 51 after
8 days). The left eye vitritis and OCT signs improved after 2 days
with reduced retinal thickness, partial restoration of EZ and ELM,
but persistent hyper-reflectivities spanning ONL and outer plexi­
form layer (Figure 1b). After 14 days, the EZ and ELM were fully
restored, with reduction of hyper-reflectivities and appearance of

CONTACT S Pockar sasa.pockar@mft.nhs.uk Manchester Royal Eye Hospital, Oxford Road, Manchester M13 9WL, UK
© 2020 Taylor & Francis Group, LLC
2 S. POCKAR ET AL.

Figure 1. Left eye macular sequential swept-source optical coherence tomography images (a-f) and wide-field retinal images at presentation (g-h). (a) OCT
demonstrating a focal area of retinal thickening nasal to the fovea with a band of inner-retinal hyper-reflectivity, particularly within the nerve fiber layer (*), disruption
of structures from the outer nuclear layer (ONL) to the ellipsoid zone (EZ) (arrow), outer retinal hyper-reflectivities and disruption of the external limiting membrane
(ELM), EZ and inter-digitation zone (IZ) (arrowhead). (b) Reduced retinal thickness, partial restoration of EZ and ELM, persistent hyper-reflectivities spanning ONL and
outer plexiform layer (*) after 2 days. (c) Reduction of hyper-reflectivities (*), posterior hyaloid vitreous deposits (arrow) after 14 days consistent with vitreous cells. (d)
A hyper-reflective inner retinal lesion, consistent with a cotton wool appeared at 1 month with no evidence of retinal necrosis (*). Evolution of the vitreo-retinal interface
was evident with posterior vitreous detachment. (e) Full resolution of the cotton-wool spot was observed after a further 2 months. (f) Complete restoration of retinal
layers after 3 months. (g) Right eye retinal imaging at presentation with extensive retinal necrosis involving all four quadrants and disease in the temporal retina
extending toward the posterior pole and macular regions. Extensive occlusive arteritis was evident. Laser scars are evident in the supero-nasal and nasal retina (*)
following prophylactic retinopexy performed in the referring center. (h) Left eye wide-field retinal imaging was normal at presentation to Manchester Uveitis Clinic. (i)
A magnified view of the left posterior pole three days after stopping aciclovir, with marked location of the OCT scans (arrow).

posterior hyaloid vitreous deposits (Figure 1c). At 1 month, a cot­ resolved within 2 months (Figure 1e). After 3 months, complete
ton-wool spot was observed in the area of previous thickening but restoration of retinal layers was observed (Figure 1f). The right eye
no other retinal structural change was evident (Figure 1d). This developed macula-off retinal detachment (RD) and underwent

vitrectomy and oil tamponade. The final VAs at 9 months were
hand movements right and 0.0 LogMar left. Long-term antiviral
maintenance therapy (aciclovir 400 mg BD) was continued.
Discussion
Acute retinal necrosis is characterized by acute panuveitis with
peri-arteritis progressing to necrotizing retinitis (and RD in up to
75% of cases) and carries a very poor prognosis. Early diagnosis
and systemic treatment are essential to control progression of
retinal necrosis, to reduce the risk of RD and optic neuropathy
and to prevent second eye involvement. Adjunctive foscarnet may
be more effective than systemic therapy alone.1
Early and isolated macular involvement is atypical in ARN,
which has a predilection for peripheral retina. Non-necrotizing
and posterior necrotizing variants are however described.2
Hizarolan et al. described atypical focal posterior pole VZV
and herpes simplex retinitis in a series of eight immunocom­
petent patients with clinically evident unilateral retinitis treated
with systemic antiviral with eventual development of retino­
choroidal scarring.3 Sequential OCT findings in macula-
involving ARN secondary to VZV are described in case reports
in patients with clinically detectable retinitis.4,5 Murata et al.
described full-thickness hyper-reflectivities and thickening in
early stages, particularly in the inner retina, with evolution to
cystic thickening in the ONL and loss of layer delineation,
disruption of EZ and IZ layers followed by necrosis (inner
then outer retina).4 In a separate case of peripheral ARN
extending within the inferior arcade, macular OCT changes
with inner retinal hyper-reflectivities and edema are described
alongside disorganization of the outer retina. Loss of the EZ
was observed in the acute stages and persisted during long-
term follow-up.5
We demonstrate the utility of SS-OCT technology for early
detection of second eye involvement, with an insight into the
pattern of disease with thickening and inner and outer-retinal
disruption plus foveal foci of hyper-reflective change within the
ONL, in the absence of clinically detectable retinitis. High-
resolution SS-OCT in viral retinitis is also useful for evaluating
the vitreo-retinal interface, with posterior hyaloid vitreous
deposits and subsequent vitreous detachment demonstrated in
our patient, and demarcating regions of abnormal retina.
Tomography was extremely valuable for evaluating response to
treatment with clear evidence of resolution of thickening and
restoration of layers, favoring a better visual prognosis. The later
appearance of a cotton-wool spot, suggesting localized altered
retinal circulation, was confirmed and monitored with OCT,
OCULAR IMMUNOLOGY AND INFLAMMATION 3
with demonstration of a focal inner retinal hyper-reflectivity
rather than retinal necrosis.
Pre-clinical OCT detection of VZV retinitis prompted urgent
intravitreal foscarnet injection to achieve immediate therapeutic
vitreous drug levels and inhibit viral replication. This, alongside
systemic aciclovir, limited the extent of disease, achieving rapid
control and full restoration of retinal structures. We suggest the
disease pattern and severity observed was influenced by the
patient initially receiving high-dose systemic antiviral therapy
to protect the eye. Furthermore, rapid intervention including
intravitreal anti-viral therapy at an early disease stage prevented
permanent tissue disruption and typical atrophy seen in ARN.
Conclusion
To the best of our knowledge, this is the first description of the
use of OCT technology to detect pre-clinical evidence of viral
retinitis in the contralateral eye during ARN. The technique is
a valuable adjunct to clinical examination for early detection of
retinal involvement and monitoring response to therapy and
we recommend routine imaging of the contralateral eye during
ARN management.
Declaration of interest
The authors report no conflicts of interest. The authors alone are respon­
sible for the content and writing of the paper.
References
1. Schoenberger SD, Kim SJ, Thorne JE, et al. Diagnosis and treatment
of acute retinal necrosis: A report by the American academy of
ophthalmology. Ophthalmology. 2017;124(3):382–392.doi:10.1016/j.
ophtha.2016.11.007.
2. Margolis R, Brasil OF, Lowder CY, et al. Multifocal posterior
necrotizing retinitis. Am J Ophthalmol. 2007;143(6):1003–1008.
doi:10.1016/j.ajo.2007.02.033.
3. Hizarolan D, Sungur G, Demir N, Kasim R, Duman S. Focal
posterior pole viral retinitis. Eur J Ophthalmol. 2010;20
(5):925–930. doi:10.1177/112067211002000518.
4. Murata K, Yamada W, Nishida T, et al. Sequential optical
coherence tomography images of early macular necrosis caused
by acute retinal necrosis in non-human immunodeficiency virus
patients. Retina. 2016;36(7):e55–7.doi:10.1097/IAE.000000000
0000972.
5. Ohtake-Matsumoto A, Keino H, Koto T, Okada AA. Spectral
domain and swept source optical coherence tomography find­
ings in acute retinal necrosis. Graefes Arch Clin Exp Ophthalmol.
2015;253(11):2049–2051. doi:10.1007/s00417-015-3051-x.