Case Report
Bilateral radiation retinopathy
17 years following radiotherapy
for nasopharyngeal carcinoma:
A diagnostic and therapeutic challenge
during COVID-19 lockdown
Koyel Chakraborty, Srikant K Padhy1,
Bhagabat Nayak, Gargi Verma
A 40‑year‑old male presented with reduced vision in the right
eye for one week. He had a history of nasopharyngeal carcinoma
for which 34‑Gy radiation was administered. The best‑corrected
visual acuity (BCVA) was 20/40 in the right eye and 20/20 in the
left eye. Anterior segment examination suggested a bilateral
early posterior subcapsular cataract. Fundoscopy revealed
bilateral localized telangiectasia and macular edema in the right
eye. Diagnosis of bilateral extremely delayed onset radiation
retinopathy with right eye macular edema was made. Three
doses of intravitreal bevacizumab injection were administered in
the right eye. The patient was lost to follow‑up due to COVID‑19
and presented with recurrence.
Key words: Radiation, recurrence, retinopathy
Radiotherapy is a well‑established line of treatment in
several neoplastic and non‑neoplastic conditions of the orbit,
head, neck, and nasopharynx. Its ophthalmic complications
include dry eye disease, blepharitis, keratoconjunctivitis,
scleral necrosis, glaucoma, cataract, optic neuropathy, and
radiation retinopathy.[1] Radiation retinopathy is a late‑onset,
slowly progressive, occlusive microangiopathy involving
retinal vasculature.[2] Factors critical for its development
are dosage, location, total amount of radiation delivered,
concurrent chemotherapy, and comorbid conditions such as
hypertension, diabetes, and collagen vascular diseases.[3] The
overall incidence has been reported to be 17%, the highest
being associated with radiation in the orbit (85.7%), followed
Access this article online
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DOI:
10.4103/ijo.IJO_1526_22
Department of Ophthalmology, All India Institute of Medical Sciences,
Bhubaneswar, Odisha, 1Vitreo-Retina Services, L. V. Prasad Eye
Institute, Bhubaneswar, Odisha, India
Correspondence to: Dr. Bhagabat Nayak, All India Institute of Medical
Sciences, Bhubaneswar ‑ 751 019, Odisha, India. E‑mail: bhagabat80@
gmail.com
Received: 25-Jun-2022 Revision: 27-Sep-2022
Accepted: 28-Oct-2022 Published: 30-Dec-2022
© 2022 Indian Journal of Ophthalmology | Published by Wolters Kluwer - Medknow
by paranasal sinuses  (45.4%), nasopharynx  (36.4%), and the
brain (3.1%).[4] The clinical course follows a log dose‑response
curve and occurs with dosages between 15 Gy and 60 Gy.[5]
The threshold of radiation has been reported to be 35Gy with
a daily fraction of 1.8–2G y in most literature.[6]
We report a case of extremely delayed onset radiation
retinopathy with recurrent macular edema (ME), presenting
17 years after exposure.
Case Report
A 40‑year‑old man presented with reduced vision in the right
eye for one week. A detailed medical history revealed that he
had nasopharyngeal carcinoma 17 years back and had received
two cycles of chemotherapy followed by 34 Gy of external beam
radiotherapy over four months. He did not have any history
of diabetes mellitus, hypertension, or immunological disorder.
The best‑corrected visual acuity  (BCVA) at presentation
was 20/40 and 20/20 in the right and left eye, respectively.
Anterior segment examination was unremarkable except for
bilateral focal posterior subcapsular cataract. Dilated fundus
evaluation revealed localized microvascular telangiectasia
distributed along the terminal blood vessels around the
fovea and elsewhere in the macula with microaneurysms and
multiple dot hemorrhages at the posterior pole in both the
eyes [Fig. 1a and c]. The right eye also had ME and a small
tortuous blood vessel with collaterals temporal to the fovea,
which was better appreciated using red‑free filter [Fig. 1b, 1d].
Fundus fluorescein angiography  (FFA) revealed bilateral
perifoveal capillary telangiectasia, pinpoint hyperfluorescence
in early phase  (microaneurysms) with late leakage, without
neovascularization [Fig. 2a, 2b]. Swept‑source optical coherence
tomography  (SS‑OCT) of the right eye revealed a subfoveal
neurosensory detachment (NSD) with pockets of intraretinal
fluid temporal to the fovea, whereas SS‑OCT was unremarkable
for the left eye [Fig. 3a, 3b]. OCT angiography (OCTA) of both
the eyes revealed abnormal telangiectatic vessels in superficial
and deep retinal vasculature with capillary dropouts and
irregular foveal avascular zone (FAZ) temporally [Fig. 4a–d].
Routine blood investigations showed a fasting blood glucose of
89 mg/dL, two‑hour postprandial blood glucose of 97 mg/dL,
glycosylated hemoglobin (HbA1c) of 5.9%, and non‑reactive
titers of HBsAg, anti‑HCV antibody, and HIV‑I and II. Blood
pressure was 128/78  mmHg, which was normal as per the
patient’s age. Based on history, clinical, imaging, angiographic,
and blood investigation findings, a diagnosis of bilateral
extremely delayed onset radiation retinopathy with right eye
ME was made.
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Cite this article as: Chakraborty K, Padhy SK, Nayak B, Verma G. Bilateral
radiation retinopathy 17 years following radiotherapy for nasopharyngeal
carcinoma: A diagnostic and therapeutic challenge during COVID‑19 lockdown.
Indian J Ophthalmol 2023;71:303-5.
304 Indian Journal of Ophthalmology Volume 71 Issue 1
a b
c d
Figure 1: Color fundus photograph of right (a) and left eye (c) shows
presence of microaneurysms, multiple dot hemorrhages (horizontal
small arrow head) at the posterior pole along with localized
microvascular telangiectasia (vertical long arrow head) distributed
along terminal blood vessels temporal to the macula, features better
appreciated using red‑free imaging (b, d)
a b
c d
e f
Figure 3: SS‑OCT of the right eye macula (a) shows intraretinal
hyporeflective spaces temporal to the fovea along with subfoveal
neurosensory detachment; left eye (b) shows normal anatomical
layers. At one‑month follow‑up post injection, right eye (c) shows
disappearance of the subfoveal neurosensory detachment with the
persistence of the intraretinal hyporeflective spaces; left eye (d) remains
the same. After third injection, right eye (e) shows significant reduction
of intraretinal hyporeflective spaces. At nine‑month follow‑up, right
eye (f) shows huge intraretinal hyporeflective cystic spaces
The presence of microaneurysms, dot hemorrhages, and
ME along with microvascular telangiectasia temporal to
the fovea led to few differential diagnoses. Macular branch
retinal venous occlusion  (BRVO) was considered because
a b
Figure 2: Fundus fluorescein angiography of the right  (a) and the
left eye (b); late‑phase delineates the microaneurysms present in the
posterior pole and temporal parafoveal telangiectatic blood vessels
a b
c d
Figure 4: OCTA image of the right eye superficial (a) and deep capillary
plexus slab (b) reveals areas of capillary dropout with an enlarged FAZ,
telangiectatic terminal blood vessel at the temporal border of the fovea,
whereas that of the left eye shows a circular normal FAZ with areas
of capillary dropouts temporal to it in the superficial capillary plexus
slab (c) and telangiectatic blood vessels in deep (d) capillary plexus slab
of the collaterals, microaneurysms, and ME. However,
absence of sclerosed vessel and delayed dye transition on
FFA ruled this out. Telangiectatic vessels temporal to the
fovea and microaneurysms in the posterior pole favored
macular telangiectasia type 2. However, dot hemorrhages and
telangiectasias outside the macula and lack of OCT features
ruled it out. Moreover, FFA in this condition characteristically
shows telangiectatic capillaries predominantly temporal to the
foveola in early phase and diffuse hyperfluorescence in late
phase. Fundus findings were also similar to non‑proliferative
diabetic retinopathy, but the patient being non‑diabetic ruled
out this differential. HIV retinopathy also mimics radiation
retinopathy and was ruled out by detailed history and negative
serum titers for HIV‑I and II.
The patient was administered one dose of intravitreal
bevacizumab (IVB) injection (1.25 mg/0.05 mL) in the right eye.
January 2023 Case Reports
At one‑month follow‑up, vision improved to 20/20p in the right
eye with OCT showing resolution of NSD, though there was
persistence of intraretinal fluid  [Fig.  3c, 3d]. Thereafter, two
more doses of IVB were administered at one‑month intervals,
and significant resolution of ME was noted after the third
dose [Fig. 3e]. He was lost to follow‑up due to the then ongoing
COVID‑19 pandemic and presented nine months later with
worsening vision in the right eye. OCT showed intraretinal cystic
spaces and focal exudates in the affected eye [Fig. 3f]. As of this
writing, repeat injection of IVB with focal laser photocoagulation
of leaky microaneurysms has been planned. The left eye macula
was without any changes till the last follow‑up.
Discussion
Radiation retinopathy usually begins within 6–12  months
after completion of radiotherapy, and once it commences,
it becomes almost irreversible. The posterior pole being the
most radiosensitive region of the retina is affected early, as in
this case. The pathogenesis appears to be related to vascular
injury, which is evident clinically as microvascular damage,
including vascular occlusion, telangiectasia, formation of
collaterals, and microaneurysms.[7] All of these findings were
present in our case. FFA typically shows areas of capillary
non‑perfusion, which is considered the gold standard for
diagnosis. Our patient had enlargement of FAZ temporally
and perifoveal capillary telangiectasia in both eyes on FFA.
One of the earliest manifestations of this disease is ME
which can be picked up on OCT.[8] Also, OCTA can detect
early vascular changes like irregular widening of FAZ in
superficial and deep layers, mild‑to‑moderate capillary
dropouts, and microaneurysms before anatomical changes
appear on OCT. Keeping the radiation dose below the
threshold limits is the only preventive measure. However, this
is not always possible in real life, especially after the sudden
hit of SARS‑CoV‑2. Stone et al.[9] showed a delay in review
of ≥8 weeks in 39.6% of patients with neovascular age‑related
macular degeneration—retinal vein occlusion  (RVO) or
diabetic macular edema (DME)—out of which 30.4% returned
for follow‑up. Even though our patient responded to three
initial doses of IVB, there was recurrence of edema due to
non‑compliance owing to the pandemic.
Conclusion
Radiation retinopathy can have late presentation, even
decades after exposure. Long‑term follow‑up is crucial in
305
patients receiving radiotherapy for head and neck carcinoma.
Multimodal imaging with FFA, OCT, and OCTA can detect
challenging cases with diagnostic dilemmas. Treatment should
be re‑initiated at the earliest in cases that have been lost to
follow‑up.
Declaration of patient consent
The authors certify that they have obtained all appropriate
patient consent forms. In the form the patient(s) has/have
given his/her/their consent for his/her/their images and other
clinical information to be reported in the journal. The patients
understand that their names and initials will not be published
and due efforts will be made to conceal their identity, but
anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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