Clinics of oncology

Case Report ISSN: 2640-1037 Volume 7

Severe Ocular Adverse Reaction Following Single Pembrolizumab Infusion: A Case Report
Nisha Nixon1*, Vaidehi Konteti2, Karan Gupta3, Anna Thompson2, Erika Damato1 and Madhavan Rajan1
1
Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
2
North Middlesex University Hospital NHS Foundation Trust, London, UK
3
University of Cambridge Clinical School, Cambridge, UK
Received: 01 July 2024 Copyright:
*
Corresponding author:
Accepted: 15 July 2024 ©2024 Nixon N, This is an open access article distribut-
Nisha Nixon,
Published: 22 July 2024 ed under the terms of the Creative Commons Attribution
Cambridge University Hospitals NHS
J Short Name: COO License, which permits unrestricted use, distribution, and
Foundation Trust, Cambridge, UK
build upon your work non-commercially.

Citation:
Nixon N. Severe Ocular Adverse Reaction Following
Single Pembrolizumab Infusion: A Case Report.
Clin Onc. 2024; 7(12): 1-4

1. Abstract tein on T cells, pembrolizumab acts to circumvent the mechanisms

1.1. Purpose: To report a case of severe sight loss following single by which cancer cells evade the body’s adaptive immune response.
infusion of pembrolzumab Though reportedly better tolerated than pre-existing chemotherapy
drugs [2], much remains unknown about immune-related adverse
1.2. Methods: Retrospective case report
events that it may precipitate. To date, pneumonitis, hepatitis, co-
1.3. Results: Ocular adverse events associated with immune litis, hypothyroidism, and cutaneous adverse events have all been
checkpoint inhibitors, due to their rarity, remain poorly charac- widely reported following pembrolizumab treatment [3]. Ocular
terised. Pembrolizumab targets the programmed cell death (PD-1) adverse events, though reported less frequently, must also be con-
protein on T cells, circumventing the mechanisms by which cancer sidered, as our case demonstrates.
cells evade the body’s adaptive immune response. To date, reports
3. Case Report
of ocular surface disease, neuro-ophthalmic complications, orbito-
pathy, retinal dysfunction and uveitis have been reported following A 78 year-old male was diagnosed with a locally advanced squa-
pembrolizumab infusion. We report the first case of severe panu- mous cell carcinoma of the oral cavity in 2020. He had a large
veitis resulting in loss of vision, following a single initial infusion primary arising from the right tongue with associated bilateral
of pembrolizumab. lymphadenopathy. Radical surgery and reconstruction would have
been extensive, and he was not fit enough for this. He underwent a
1.4. Conclusion: The case serves as a heartening reminder of the
short course of palliative radiotherapy to the macroscopic disease
need for prompt reporting of visual symptoms, recognition of oc-
with a margin only, and a complete clinical response was achieved.
ular immune-related adverse events and a multi-disciplinary ap-
The radiotherapy field did not approach the eyes (Figure 1). In
proach between oncology and ophthalmology in patients receiving
2023, he reported worsening symptoms, including dysphagia and
immunotherapy for cancer treatment.
right-sided facial swelling. Serial imaging confirmed radiological
2. Background progression and he was commenced on first-line palliative im-
Pembrolizumab was approved as a first-line therapeutic agent for munotherapy with pembrolizumab. His past medical history was
unresectable or metastatic squamous cell carcinoma of the head otherwise unremarkable, and his past ocular history included pre-
and neck by NICE in 2020 [1]. Since then, it has been a central vious left eye cataract surgery only. On the evening following his
treatment option for a cohort of patients who were previously lim- first pembrolizumab infusion, he developed a severe headache,
ited to a small selection of chemotherapy agents. An IgG4 mono- followed by left eye redness, periocular swelling and blurring of
clonal antibody targeting the programmed cell death (PD-1) pro- vision, progressing to complete loss of vision in the left eye two
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Volume 7 Issue 12 -2024 Case Report

days later. He presented to the Emergency Department three days with an initial working diagnosis of orbital cellulitis with possi-
after the infusion, at which time he had severe left eye pain and ble intraocular infection. Intravitreal injection of vancomycin and
loss of vision. On examination, he was afebrile and systemically ceftazidime was administered and a sample of vitreous sent to Mi-
well. His Snellen visual acuity was 6/9 in the right eye, and no crobiology. After all cultures were proven negative, 48 hours after
perception of light in the left eye. He had no proptosis and intraoc- presentation and after minimal improvement on antibiotic therapy,
ular pressures were normal. There was marked left eyelid swelling, a revised diagnosis of likely immune-related adverse event in re-
conjunctival chemosis, redness (Figure 2), and an intense fibrinous sponse to pembrolizumab was made. Antibiotics were discontin-
and haemorrhagic inflammatory reaction in the anterior chamber ued, and oral prednisolone at a dose of 1mg/kg was commenced,
with small hypopyon. A haemorrhagic vitreous opacity obscured alongside topical steroid and atropine eye drops. Within one week
the view of the retina. The right eye exam was unremarkable, with of starting steroid treatment, the left eye pain, eyelid swelling and
healthy retina and optic nerve. Ultrasound B scan of the left eye conjunctival chemosis has subsided completely (Figure 3). The
was suggestive of haemorrhagic choroidal effusions and scleritis. anterior chamber fibrinous inflammatory reaction had lessened,
Blood tests revealed a white cell count 8.4 x109/L, platelets 475 and the haemorrhagic vitreous opacity was showing consolidation.
x109/L, CRP 34mg/L and albumin of 30g/L. MRI imaging indicat- However, the patient’s visual acuity in the left eye remains at no
ed inflammatory change throughout the left orbit associated with perception of light. Pembrolizumab treatment has been discontin-
a haemorrhagic choroidal effusion. On admission, intravenous ued, and the patient remains on best supportive care.
antibiotics (metronidazole and ceftriaxone) were commenced,

Figure 1: Colour wash of radiotherapy plan, showing prescribed volume (36Gy) in red and low dose (5Gy) in blue. The eyes received no dose of
radiotherapy.

Figure 2: Left eyelid swelling, conjunctival chemosis and injection on initial presentation.

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Volume 7 Issue 12 -2024 Case Report

Figure 3: Complete resolution of left eyelid swelling and conjunctival cheimosis 6 days after commencement of oral steroid therapy.

4. Discussion picture of optic neuropathy in addition to severe inflammation re-

Pembrolizumab is a relatively recent addition to the armoury used sponsible for sight loss in our case. Such acute-onset sight loss
against metastatic and unresectable recurrence of head and neck with panuveitis occurring after the first dose of pembrolizumab
squamous cell carcinoma. As an immune checkpoint inhibitor tar- infusion, though representing the first reported case to date, holds
geting the programmed cell death (PD-1) protein on T cells, it is implications for pre-treatment counselling and post-treatment
able to block the downregulation of the adaptive immune system monitoring. Though many ocular immune-related adverse events
and augment the attack on tumour cells. However, this disruption are mild and do not necessitate discontinuation of therapy [8],
of usual immune regulation has led to increasing reports of im- prompt recognition of severe ocular symptoms, by both patients
mune-related adverse events associated with pembrolizumab, as and healthcare professionals, and appropriate multi-disciplinary li-
well as other immune checkpoint inhibitors [4]. Ocular immune-re- aison between oncology and ophthalmology may allow for earlier
lated adverse events comprise a small proportion of these adverse initiation of treatment and prevention of sight loss [9].
events, and remain poorly characterised, yet can have wide-rang- 5. Learning Points
ing and potentially sight-threatening effects. Martens et al. (2023) • Immune checkpoint inhibitors such as pembrolizumab
[5] categorise these ocular adverse events into (i) uveitis, (ii) neu- may result in severe ocular inflammation and sight loss.
ro-ophthalmic (myaesthaenia gravis, optic nerve or other cranial Both physicians and patients need to be aware of this rare,
nerve disorders), (iii) orbital disorders (orbital inflammation, my- but serious, risk.
opathy), (iv) retinal dysfunction, and (v) ocular surface disorders
In patients receiving cancer immunotherapy and presenting with
(dry eye disease, blepharitis, conjunctivitis, episcleritis, scleritis,
ocular symptoms, a multi-disciplinary approach between oncol-
keratitis).
ogy and ophthalmology can allow for early identification of im-
The most common ocular immune-related adverse event associat- mune-related adverse events and initiation of treatment.
ed with pembrolizumab is uveitis, with pembrolizumab-associated
References
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a scoping review. J Ophthalmic Inflamm Infect. 2023; 13(1): 5.

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