Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations

Atul Jain, Sophaktra Chea, Wataru Matsumiya, M Sohail Halim, Çigdem Yaşar, Guoping Kuang, Yasir J Sepah, Arshad M Khanani, Diana V Do, Quan Dong Nguyen, Atul Jain, Sophaktra Chea, Wataru Matsumiya, M Sohail Halim, Çigdem Yaşar, Guoping Kuang, Yasir J Sepah, Arshad M Khanani, Diana V Do, Quan Dong Nguyen

Abstract

Purpose: To describe a case of unilateral retinal arteriolar occlusion following multiple intravitreal brolucizumab injections for neovascular age-related macular degeneration (nAMD).

Observations: A 92-year-old Caucasian woman presented with blurry vision in her left eye (OS) after receiving the third dose of intravitreal brolucizumab. At the time of presentation, visual acuity (VA) was 20/40 in her right eye (OD) and had decreased from 20/150 to count finger (CF) at 1-foot OS. On examination, there was no evidence of active inflammation in the anterior chamber OU. Dilated fundus examination showed no vitritis in OD and 1+ vitreous cells OS, flame-shaped hemorrhage at the superior optic disc margin, and retinal whitening surrounding the proximal portion of the supero-temporal branch of the central retinal artery. There were drusen in OS and retinal pigment epithelial (RPE) changes in the maculae of OU. Intra-arteriolar greyish deposits were seen OS. Fluorescein angiography (FA) showed hyper-fluorescence in the maculae corresponding to fibrovascular pigment epithelial detachments (PED) OU. No peri-vascular leakage was noted OU. Delayed filling of multiple arterioles in early and late phases OS was observed on FA. The patient was diagnosed with retinal arteriolar occlusion associated with repeated intravitreal brolucizumab administrations.

Conclusion: Retinal arteriolar occlusion with severe vision loss, possibly secondary to inflammatory responses, can occur after subsequent intravitreal brolucizumab injections, even if no inflammation occurred after initial administrations. Vaso-occlusive disease should be considered as a potential ocular complication, with acute as well as delayed onset, following intravitreal brolucizumab therapy.

Keywords: Age-related macular degeneration; Brolucizumab; Intravitreal; Neovascular; Retinal occlusive vasculitis; Retinal vasculitis; Vaso-occlusion.

Conflict of interest statement

The authors declare that there are no conflicts of interest related to this manuscript.

© 2020 Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
Fundus photograph (FP) of both eyes. FP of the right eye before (1A) and after (1B–1C) bevacizumab injection are within normal limits. Left eye before (1D) the third intravitreal brolucizumab injection showing drusen (yellow arrow); three weeks post-third intravitreal brolucizumab injection (1E) showing drusen (yellow arrow), whitish lesions near the disc (red arrow), small intra-arteriolar greyish depositions (black arrow); and four weeks post-third intravitreal brolucizumab injection (1F) showing whitish lesions near disc (red arrow), small intra-arteriolar greyish depositions (black arrow). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
Fig. 2
Fig. 2
Optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany) of the right (OD) and left (OS) eyes. OCT of OD after multiple intravitreal bevacizumab injections (2A, 2C, 2E). Before the third intravitreal brolucizumab injection in OS (2B), three weeks post-third intravitreal brolucizumab injection (2D) and four weeks post-third intravitreal brolucizumab injection (2F). Pigmented epithelial detachment can be seen at all visits in both OD and OS (red arrow). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
Fig. 3
Fig. 3
Fluorescein angiography of right eye (OD) post-bevacizumab injection (top row) and post-third intravitreal brolucizumab injection (bottom row) in left eye (OS). No leakage of optic nerve and peri-vasculature can be seen in OD (3A-3C). Hyper-fluorescence in the peri-foveal region with no active leakage can be seen OU (white arrows). Delayed arteriolar filling in early phase (yellow arrow) can be seen in early phase FA in OS (3D). Hyper-fluorescence of the superior retinal arteriole near the optic disc (red arrows) can be seen without leakage in mid to late FA in OS (3E-3F). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

References

    1. Hernandez-Pastor L.J., Ortega A., Garcia-Layana A., Giraldez J. Ranibizumab for neovascular age-related macular degeneration. Am J Health Syst Pharm: Offc J Am Soc Health Sys Pharama. 2008;65:1805–1814.
    1. Morris B., Imrie F., Armbrecht A.M., Dhillon B. Age-related macular degeneration and recent developments: new hope for old eyes? Postgrad Med. 2007;83:301–307.
    1. Wong W.L., Su X., Li X. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob health. 2014;2:e106–e116.
    1. Dugel P.U., Jaffe G.J., Sallstig P. Brolucizumab versus aflibercept in participants with neovascular age-related macular degeneration: a randomized trial. Ophthalmology. 2017;124:1296–1304.
    1. Dugel P.U., Koh A., Ogura Y. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2020;127:72–84.
    1. Markham A. Brolucizumab: first approval. Drugs. 2019;79:1997–2000.
    1. American Society of Retina Specialists Beovu update for ASRS members. Published February 23, 2020 and March 30, 2020.
    1. Holz F.G., Dugel P.U., Weissgerber G. Single-chain antibody fragment VEGF inhibitor RTH258 for neovascular age-related macular degeneration: a randomized controlled study. Ophthalmology. 2016;123:1080–1089.
    1. Dugel P.U. Expanded week 96 safety outcomes: analysis of pooled data from HAWK & HARRIER studies. Presented at the 2020 Meeting of the Macula Society, March 19 to 22, San Diego, California.
    1. Nguyen Q.D., Das A., Do D.V. Brolucizumab: evolution through preclinical and clinical studies and the implications for the management of neovascular age-related macular degeneration. Ophthalmology. 2020 [Epub ahead of print]
    1. Busbee B.G., Ho A.C., Brown D.M. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2013;120:1046–1056.
    1. Sepah Y.J., Sadiq M.A., Boyer D. Twenty-four-month outcomes of the ranibizumab for edema of the macula in diabetes - protocol 3 with high dose (READ-3) study. Ophthalmology. 2016;123:2581–2587.
    1. Heier J.S., Korobelnik J.F., Brown D.M. Intravitreal aflibercept for diabetic macular edema: 148-week results from the VISTA and VIVID studies. Ophthalmology. 2016;123:2376–2385.
    1. Kaiser P.K., Brown D.M., Zhang K. Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results. Am J Ophthalmol. 2007;144:850–857.
    1. Mitchell P., McAllister I., Larsen M. Evaluating the impact of intravitreal aflibercept on diabetic retinopathy progression in the VIVID-DME and VISTA-DME studies. Ophthalmol Retina. 2018;2:988–996.
    1. Nguyen Q.D., Brown D.M., Marcus D.M. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119:789–801.
    1. Heier J.S., Brown D.M., Chong V. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119:2537–2548.
    1. Data on File. Regeneron Pharmaceuticals, Inc. Tarrytown, NY 10591.
    1. Data on File. Internal Sales Data. Novartis Pharmaceuticals Corporation; March 2020.

Source: PubMed

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