Intraocular Inflammation Following Intravitreal Injection of Anti-VEGF Medications for Neovascular Age-Related Macular Degeneration

Knickelbein, Jared E.; Chew, Emily Y.; Sen, H. Nida

doi:10.3109/09286586.2015.1122067

Cited by 11 publications

(6 citation statements)

References 6 publications

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“…SII (also termed pseudoendophthalmitis) is characterized by acute-onset intraocular inflammation without infection that resolves without antibiotic treatment. The reported incidence of anti-VEGF associated SII varies by study from 0.02 to 0.37% [27,28]. Presentation usually occurs between 24 h and seven days from the inciting injection [29][30][31].…”

Section: Epidemiology and Presentationmentioning

confidence: 99%

Inflammatory Complications of Intravitreal Anti-VEGF Injections

Cox

Eliott

Sobrin

2021

JCM

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Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents is a commonly used therapy for numerous retinal diseases. The most commonly used of these medications are bevacizumab, ranibizumab, aflibercept, and brolucizumab. However, intravitreal administration of these agents is also associated with several inflammatory and non-inflammatory adverse events. The three inflammatory adverse events are sterile intraocular inflammation, brolucizumab-associated retinal vasculitis, and post-injection endophthalmitis. This narrative review summarizes the current literature regarding these conditions, including their epidemiology, presentation, management, outcomes, and pathogenesis. The inflammatory adverse events also share a number of overlapping features, which can make them difficult to discern from one another in a clinical context. This review discusses certain distinguishing features of these conditions that may aid providers in discerning between them and establishing the correct diagnosis.

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Section: Epidemiology and Presentationmentioning

confidence: 99%

Inflammatory Complications of Intravitreal Anti-VEGF Injections

Cox

Eliott

Sobrin

2021

JCM

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“…Furthermore, there was an increased risk of developing retinal scarring and geographic atrophy in nAMD patients 2 to 5 years after initiating treatment [ 14 ]. Complications such as vitreous and subconjunctival hemorrhage, fluid accumulation under the fovea, increased intraocular pressure, endophthalmitis, and ocular inflammation have also been described [ 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

New and Innovative Treatments for Neovascular Age-Related Macular Degeneration (nAMD)

Patel

Sheth²

2021

JCM

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Age-related macular degeneration (AMD) is one of the most common causes of vision loss. Advanced forms of AMD are seen in primarily two types—neovascular AMD (nAMD) with the presence of choroid neovascularization and non-neovascular AMD (nnAMD) with geographic atrophy. Neovascular AMD is characterized by choroidal neovascularization (CNV), which leads to a cascade of complications, including exudation, leakage, and ultimately fibrosis with photoreceptor loss. Inhibition of VEGF represents the current standard of care. However, there is a tremendous gap between the outcomes in randomized clinical trials and real-world settings. New agents for nAMD might offer the potential to improve treatment outcomes and reduce treatment of frequent intravitreal injections. We summarize all the newer molecules, their pivotal clinical trial results, and their unique mechanisms of action; these include longer-acting agents, combination strategies, sustained release, and genetic therapies.

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“…Due to the lack of the Fc antibody portion in the ranibizumab molecule, restricted activation of Fc receptors by ranibizumab was hypothesized to be responsible for these differences (Knickelbein et al. 2016; Souied et al. 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Non-infectious intraocular inflammation in association with intravitreal ranibizumab was reported to be a rare event, occurring at low rates ranging from 0.005% to 1.9% depending on the study (Anderson et al 2021), and to belessfrequentwithranibizumabthanwith bevacizumab (Sigford et al 2015;Knickelbein et al 2016;Williams et al 2016;Anderson et al 2021) or aflibercept (Knickelbein et al 2016;Souied et al 2016;Williams et al 2016;Anderson et al 2021). Due to the lack of the Fc antibody portion in the ranibizumab molecule, restricted activation of Fc receptors by ranibizumab was hypothesized to be responsible for these differences (Knickelbein et al 2016;Souied et al 2016). Brolucizumab does, like ranibizumab, not have an Fc portion, but nevertheless seems to provoke immunogenicity to a larger degree than ranibizumab.…”

Section: Discussionmentioning

confidence: 99%

Anti‐drug antibodies to brolucizumab and ranibizumab in serum and vitreous of patients with ocular disease

Busch

Pfeil

Dähmcke

et al. 2022

Acta Ophthalmologica

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Purpose Postapproval reports of intraocular inflammation (IOI) and occlusive retinal vasculitis following intravitreal brolucizumab are accumulating. A role of anti‐drug antibodies (ADAs) to brolucizumab is under current scientific discussion. The purpose of the present study was to measure brolucizumab ADAs in a cross‐sectional ophthalmic patient population and to compare the occurrence of brolucizumab ADAs with that of ranibizumab ADAs. Methods One hundred and ninety‐two serum samples and 54 vitreous samples were collected from patients with a range of eye diseases including neovascular age‐related macular degeneration (AMD), diabetic retinopathy, retinal vein occlusion, cataract, glaucoma, dry eye disease, macular hole, epiretinal membranes and intraocular lens (IOL) dislocation. Serum and vitreous samples were analysed for immune globuline (Ig) G ADAs to brolucizumab and ranibizumab using indirect enzyme‐linked immunosorbent assay (ELISA). Optical Density (OD) was read at 450 nm (wavelength correction at 550 nm) for ADA level measurements. Results Presence of brolucizumab ADAs was observed in patients with and without prior brolucizumab exposure. Both the frequency of notable ADA signals (OD > 0.1) and the mean ADA signal in serum samples were higher for brolucizumab than for ranibizumab. Two patients who experienced severe IOI and occlusive retinal vasculitis following intravitreal brolucizumab had high brolucizumab ADA serum levels. In one of these two patients, high brolucizumab ADA levels were also found in vitreous. Another patient developed moderate IOI without retinal vasculitis in the presence of low brolucizumab ADA serum levels. Overall, notable brolucizumab ADA levels were less frequent in vitreous than in the corresponding serum samples but with a tendency for higher prevalence in vitreous from patients with diabetic retinopathy. Conclusion Brolucizumab ADAs occur with significant prevalence in a typical ophthalmic patient population and may represent a risk factor for IOI and occlusive retinal vasculitis following brolucizumab.

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Intraocular Inflammation Following Intravitreal Injection of Anti-VEGF Medications for Neovascular Age-Related Macular Degeneration

Cited by 11 publications

References 6 publications

Inflammatory Complications of Intravitreal Anti-VEGF Injections

Inflammatory Complications of Intravitreal Anti-VEGF Injections

New and Innovative Treatments for Neovascular Age-Related Macular Degeneration (nAMD)

Anti‐drug antibodies to brolucizumab and ranibizumab in serum and vitreous of patients with ocular disease

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