Open Access

Various clinical presentations of uveitis associated with durvalumab treatment

Nika Vrabic
Nika Vrabic
, 
Ana Fakin
Ana Fakin
, 
Polona Jaki Mekjavic
Polona Jaki Mekjavic
, 
Urska Janzic
Urska Janzic
, 
Martina Vrankar
Martina Vrankar
 and 
Natasa Vidovic Valentincic
Natasa Vidovic Valentincic
   | Apr 12, 2022
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Article Category: review article
Published Online: Apr 12, 2022
Page range: 129 - 137
Received: Nov 24, 2021
Accepted: Jan 10, 2022
DOI: https://doi.org/10.2478/raon-2022-0007
© 2022 Nika Vrabic, Ana Fakin, Polona Jaki Mekjavic, Urska Janzic, Martina Vrankar, Natasa Vidovic Valentincic, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Case I. Fundoscopy, at presentation, on one-week and five-week follow-up. Follow-up images show diminishment of vitreous haze and regression of optic disc swelling.OD(R) = oculus dexter (right); OS(L) = oculus sinister (left)
Case I. Fundoscopy, at presentation, on one-week and five-week follow-up. Follow-up images show diminishment of vitreous haze and regression of optic disc swelling.OD(R) = oculus dexter (right); OS(L) = oculus sinister (left)

Figure 2

Case I. Optical coherence tomography (OCT) of optic discs. Optic disc drusen at presentation and on a five-week follow-up. No alteration in optic disc drusen size is visible. Up images show diminishment of vitreous haze and regression of optic disc swelling.OD(R) = oculus dexter (right); OS(L) = oculus sinister (left)
Case I. Optical coherence tomography (OCT) of optic discs. Optic disc drusen at presentation and on a five-week follow-up. No alteration in optic disc drusen size is visible. Up images show diminishment of vitreous haze and regression of optic disc swelling.OD(R) = oculus dexter (right); OS(L) = oculus sinister (left)

Figure 3

Case I. Fluorescein angiography at presentation. Early and late frames. Contrast blockage in the upper temporal part of the right optic disc (white arrow), corresponding to a peripapillary haemorrhage. Hypofluorescent dots (black arrow) corresponded to hyperreflective spots on optical coherence tomography (OCT). Fluorescein angiography five weeks on methylprednisolone treatment. Early and late frames. Diminishment of the contrast blockage in the upper temporal part of the right optic disc (white arrow) corresponding to a peripapillary haemorrhage. Hypofluorescent dots (black arrow) are less prominent.OD(R) = oculus dexter (right); OS(L) = oculus sinister (left)
Case I. Fluorescein angiography at presentation. Early and late frames. Contrast blockage in the upper temporal part of the right optic disc (white arrow), corresponding to a peripapillary haemorrhage. Hypofluorescent dots (black arrow) corresponded to hyperreflective spots on optical coherence tomography (OCT). Fluorescein angiography five weeks on methylprednisolone treatment. Early and late frames. Diminishment of the contrast blockage in the upper temporal part of the right optic disc (white arrow) corresponding to a peripapillary haemorrhage. Hypofluorescent dots (black arrow) are less prominent.OD(R) = oculus dexter (right); OS(L) = oculus sinister (left)

Figure 4

Case I. Optical coherence tomography (OCT) of optic discs, at presentation, one week on methylprednisolone treatment, five weeks on methylprednisolone treatment. Follow-up shows regression of optic disc swelling.OD(R) = oculus dexter (right); OS(L) = oculus sinister (left)
Case I. Optical coherence tomography (OCT) of optic discs, at presentation, one week on methylprednisolone treatment, five weeks on methylprednisolone treatment. Follow-up shows regression of optic disc swelling.OD(R) = oculus dexter (right); OS(L) = oculus sinister (left)

Figure 5

Case II. (A) Fundoscopy, prior to non-small cell lung cancer diagnosis in 2013: posterior pole and peripheral retinal changes. (B) Colour fundus photography at presentation in March 2021: multiple flat, grey-white lesions (black arrows) are visible at presentation. (C) Three weeks on methylprednisolone treatment in April 2021: a diminishment of lesions (white arrows) is observed.OD = oculus dexter; OS(L) = oculus sinister
Case II. (A) Fundoscopy, prior to non-small cell lung cancer diagnosis in 2013: posterior pole and peripheral retinal changes. (B) Colour fundus photography at presentation in March 2021: multiple flat, grey-white lesions (black arrows) are visible at presentation. (C) Three weeks on methylprednisolone treatment in April 2021: a diminishment of lesions (white arrows) is observed.OD = oculus dexter; OS(L) = oculus sinister

Figure 6

Case II. (A) Macular optical coherence tomography (OCT) presentation and (B) two weeks on methylprednisolone treatment. Loss of ellipsoid zone and hyperreflective haze in outer plexiform and outer nuclear layers is evident at presentation. Indocyanine angiography at presentation shows hypofluorescent lesions corresponding to ellipsoid zone disruptions (white arrows). Two weeks on methylprednisolone treatment ellipsoid zone appears granular.OD = oculus dexter; OS(L) = oculus sinister
Case II. (A) Macular optical coherence tomography (OCT) presentation and (B) two weeks on methylprednisolone treatment. Loss of ellipsoid zone and hyperreflective haze in outer plexiform and outer nuclear layers is evident at presentation. Indocyanine angiography at presentation shows hypofluorescent lesions corresponding to ellipsoid zone disruptions (white arrows). Two weeks on methylprednisolone treatment ellipsoid zone appears granular.OD = oculus dexter; OS(L) = oculus sinister

Figure 7

Case II. Fluorescein angiography at presentation, early and late frames. Note surface capillary net dilatation and late staining of the papilla and hypofluorescent areas on the posterior pole and periphery. Indocyanine angiography at presentation showing hypofluorescent lesions.OD = oculus dexter; OS(L) = oculus sinister
Case II. Fluorescein angiography at presentation, early and late frames. Note surface capillary net dilatation and late staining of the papilla and hypofluorescent areas on the posterior pole and periphery. Indocyanine angiography at presentation showing hypofluorescent lesions.OD = oculus dexter; OS(L) = oculus sinister

Figure 8

Case II. Fundus autofluorescence images at presentation show no pathologic changes. Hyperautofluorescent spots are visible three weeks on methylprednisolone treatment.AF = fundus autofluorescence; OD = oculus dexter; OS(L) = oculus sinister
Case II. Fundus autofluorescence images at presentation show no pathologic changes. Hyperautofluorescent spots are visible three weeks on methylprednisolone treatment.AF = fundus autofluorescence; OD = oculus dexter; OS(L) = oculus sinister

Published cases reporting uveitis secondary to durvalumab (PD-L1 inhibitor) treatment

Author, year Number of cases reported Indication Ocular inflammation specification (% eyes) Treatment Discontinuing immune checkpoint inhibitor
Dow et al. 20206 3 n/a Anterior uveitis 80%Posterior uveitis 20% Local corticosteroidSystemic corticosteroid No
Parikh et al., 20207 1 Non-small cell lung cancer Anterior uveitis Local corticosteroid Yes
Andrade et al., 20208 1 Non-small cell lung cancer Retinal vasculitis Systemic corticosteroid Yes
Vrabic et al., 2021 2 Small cell lung cancer, non-small cell lung cancer Intermediate uveitis, Posterior uveitis Systemic corticosteroid Yes

Published cases reporting uveitis and optic disc oedema/papillitis secondary to other immune checkpoint inhibitors

Author, year Immune checkpoint inhibitor Target receptor Cancer diagnosis Clinical findings at presentation Complications Initial treatment Discontinuing immune checkpoint inhibitor
Hahn et al., 20169 Ipilimumab CTLA-4 Malignant melanoma AC inflammation, keratic precipitates Panuveitis, papillitis, intraretinal, subfoveal fluid Topical prednisolone acetate, brimonidine tartrate timolol maleate, oral prednisolone 20 mg/day Discontinued
Aaberg et al., 201710 Pembrolizumab PD-1 Uveal melanoma AC inflammation, vitreous cells and haze Optic disc oedema, posterior uveitis, retinal vasculitis Intraocular dexamethasone implant No.
Wang et al., 201911 Nivolumab PD-1 Renal carcinoma AC inflammation, keratoprecipitates, posterior synechiae, vitreous floaters Panuveitis, papillitis, serous retinal detachment Intravenous methylprednisolone 500 mg/day, followed by oral prednisolone 30 mg/day tapered over 2 months; recurrence of uveitis managed with periocular methylprednisolone, and intraocular dexamethasone implant Discontinued, resumed 6 weeks after discontinuation, recurrence of uveitis 2 weeks after resumption
Reid et al., 201812 Pembrolizumab PD-1 Malignant melanoma AC vitreous inflammation, cells, choroidal thickening, posterior synechiae Panuveitis, optic disc oedema, hypotony Oral prednisolone 75 mg/day 7 days, tapered over 3 weeks Discontinued after 12 months commenced on nivolumab therapy
Navarro- Perea et al., 201913 Pembrolizumab PD-1 Malignant melanoma AC inflammation, irido-crystalline synechiae Optic disc oedema Topical dexamethasone, cyclopentolate, tropicamide, phenylephrine, oral prednisolone 40 mg/day tapered over 2 months Discontinued, replaced by vemurafenib and cobimetinib
Sun et al., 20205 Nivolumab PD-1 Malignant melanoma AC inflammation, vitreous cells, and haze Optic disc oedema, ocular hypertension Topical prednisolone acetate, oral prednisolone 60 mg/day n/a
Sun 2020et 5 al., Pembrolizumab PD-1 Malignant melanoma AC inflammation Hypotony, Papillitis Topical difluprednate, subtenon triamcinolone acetonide n/a
Sun et al., 20205 Ipilimumab PD-1 Malignant melanoma AC inflammation, vitreous cells Macular oedema, Papillitis Tiamcinolonetransseptal followed by retrobulbar) n/a
Kim et al., 202014 Pembrolizumab PD-1 Renal carcinoma n/a Panuveitis, papillitis Topical steroid, posterior subtenon triamcinolone injection Discontinued
Kim 2020et 14 al., Pembrolizumab PD-1 Uveal melanoma n/a Panuveitis, papillitis Systemic steroid Discontinued
Kim 2020et 14 al. Pembrolizumab PD-1 Lung cancer n/a Panuveitis, uveal effusion papillitis, Systemic steroid Discontinued
Kikuchi et al. 202015 Nivolumab PD-1 Hypopharyngeal cancer Granulomatous mutton-fat keratic precipitates, AC inflammation, posterior synechiae Panuveitis, papillitis, serous retinal detachment; Vogt- Koyanagi-Harada disease-like uveitis Sub-tenon triamcinolone acetonide, followed by methylprednisolone 1000 mg/day 3 days, followed by oral methylprednisolone 50 mg/day tapered by 5 mg every week Discontinued due to the patient’s deteriorating health
Vrabic et al. durvalumab PDL-1 NSCLC AC inflammation, vitreous cells Intermediate uveitis, optic dics oedema Systemic steroid 500 mg/day 3 days, followed by oral methylprednisolone 48 mg/day tapered over 6 weeks Discontinued
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