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 Table of Contents  
Year : 2023  |  Volume : 3  |  Issue : 2  |  Page : 433-435

Response of a single-dose intravitreal brolucizumab in type 3 macular neovascularization

1 Department of Vitreoretinal Services, Retina Institute of Bengal, Pradhan Nagar, Siliguri, West Bengal, India
2 Shantilal Shanghvi Eye Institute, Mumbai, Maharashtra, India

Date of Submission06-Nov-2022
Date of Acceptance14-Dec-2022
Date of Web Publication28-Apr-2023

Correspondence Address:
Somnath Chakraborty
Retina Institute of Bengal, Pradhan Nagar, Siliguri - 734 003, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJO.IJO_2957_22

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The authors describe a case of an 82-year-old female with type 3 macular neovascularization (MNV) who underwent a single-dose of intravitreal injection (IVI) of brolucizumab at baseline. The patient demonstrated significant visual improvement from 20/400 at baseline to 20/32 at 3 months without any significant adverse events. Notably, there was complete resolution of the subretinal fluid (SRF), intraretinal fluid (IRF), and subretinal hyperreflective material (SHRM) at 1 month postinjection, which was maintained for up to 3 months. Further prospective studies with a larger sample size are warranted to better understand the morphological and visual responses of type 3 MNV to brolucizumab therapy.

Keywords: Anti-vascular endothelial growth factor, brolucizumab, macular neovascularization, retinal angiomatous proliferation

How to cite this article:
Chakraborty S, Sheth JU. Response of a single-dose intravitreal brolucizumab in type 3 macular neovascularization. Indian J Ophthalmol Case Rep 2023;3:433-5

How to cite this URL:
Chakraborty S, Sheth JU. Response of a single-dose intravitreal brolucizumab in type 3 macular neovascularization. Indian J Ophthalmol Case Rep [serial online] 2023 [cited 2023 Jun 5];3:433-5. Available from: https://www.ijoreports.in/text.asp?2023/3/2/433/375005

Type 3 macular neovascularization (MNV), formerly known as retinal angiomatous proliferation (RAP), is a distinctive type of neovascular age-related macular degeneration (nAMD) accounting for 10%–40% of these cases.[1] Having two neovascular elements, one in the choroid and the other in the deep retina, gives type 3 MNV its distinctive feature. Currently, the preferred treatment for MNV is intravitreal anti-vascular endothelial growth factor (anti-VEGF) medication, which has also been utilized extensively for type 3 MNV.[2]

Brolucizumab, a US Food and Drug Administration (FDA)-approved anti-VEGF agent, is a humanized single-chain antibody fragment that inhibits all VEGF-A isoforms.[3] In the HAWK and HARRIER trials, brolucizumab was demonstrated to be noninferior to aflibercept in terms of visual acuity outcomes with comparatively better anatomical outcomes.[4] However, these landmark trials did not evaluate the variations in therapeutic responses based on the type of MNV, specifically, type 3 networks. In our case report, we illustrate the efficacy of intravitreal injection (IVI) of brolucizumab in a patient with type 3 MNV.

  Case Report Top

An 82-year-old female presented with diminution of vision in the right eye (OD) for 3 months. Her best-corrected visual acuity (BCVA) was 20/400 in OD and 20/20 in the left eye (OS). Both eyes' (OU) anterior segments showed good pseudophakia. Fundus examination of OD showed presence of exudative maculopathy with a diving retinal vessel, while OS demonstrated dry AMD changes [Figure 1]a and [Figure 1]b. On spectral-domain optical coherence tomography (SD-OCT), there was presence of fibrovascular pigment epithelial detachment (PED), with subretinal fluid (SRF), intraretinal fluid (IRF), subretinal hyperreflective material (SHRM), and an intraretinal hyperreflective lesion, suggestive of the neovascularization in OD [Figure 1]c. On fundus fluorescein angiography (FFA), OD showed the presence of significant subretinal and intraretinal leakage [Figure 1]d. Based on multimodal imaging, the patient was diagnosed with type 3 MNV in OD and underwent IVI of brolucizumab.
Figure 1: Baseline CFP demonstrating the presence of exudative maculopathy in the right eye (OD) with a diving retinal vessel (yellow arrow) (a) and dry AMD changes in the left eye (OS) (b). The baseline SD-OCT of OD (c) demonstrates the presence of IRF, SRF, SHRM, PED, and an intraretinal hyperreflective lesion suggestive of the neovascularization (c). FFA of OD at baseline illustrates the presence of subretinal and intraretinal leakage (d). After undergoing treatment with IVI of brolucizumab, there was complete resolution of IRF and SHRM, with a notable reduction in SRF and PED morphology on the SD-OCT at 1 month (e), week 4 (b), week 8 (c), and week 12 (d). At 3 months, the SRF too resolved completely with a further reduction in the PED (f). AMD = age-related macular degeneration, CFP = color fundus photographs, FFA = fundus fluorescein angiography, IRF = intraretinal fluid, IVI = intravitreal injection, PED = pigment epithelial detachment, SD-OCT = spectral-domain optical coherence tomography, SHRM = subretinal hyperreflective material, SRF = subretinal fluid

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After 1 month, the OS BCVA improved considerably to 20/63. On SD-OCT, there was complete resolution of the IRF and SHRM, with a significant reduction in PED morphology [Figure 1]e. The patient had trace residual SRF and was advised a second dose of IVI brolucizumab. However, the patient refused further treatment due to economic constraints. The patient was observed and at 3 months, she showed further visual improvement to 20/32. On SD-OCT, there was complete resolution of the residual SRF noted at 1 month [Figure 1]f. The PED morphology too improved significantly [Figure 1]f. There were no adverse ocular or systemic effects reported. The serial SD-OCT images from all visits are portrayed in [Figure 1].

  Discussion Top

In our unique case report, we demonstrate the therapeutic response of a single dose of brolucizumab injection in a patient with type 3 MNV that lasted up to 3 months. Excellent visual improvement was noted along with a notable morphological response on SD-OCT, lasting up to 3 months. Additionally, no ocular or systemic adverse events were observed.

Type 3 MNV/RAP is a form of nAMD characterized by intraretinal neovascularization leading to retinal–choroidal anastomosis.[2] Type 3 MNV is considered to have a less-favorable natural course than other kinds of nAMD that cause visual impairment.[2],[5] Progression to poor vision in stage I and stage II RAP-affected eyes is usually seen within 3 months in patients with quick progression and within 1 year in patients with slow progression.[6] Thus, early treatment with a potent anti-VEGF agent is imperative for optimal therapeutic outcomes. It has been shown that aflibercept is just as effective as ranibizumab for treating nAMD, while requiring fewer injections.[7] In the cohort of RAP eyes within the Comparison of AMD Treatments Trials (CATT), it was demonstrated that the likelihood of fluid, fluorescein angiography (FA) leakage, scarring, and SHRM was lower and the likelihood of geographic atrophy (GA) was higher in eyes with RAP at 1 and 2 years following the start of anti-VEGF treatment.[1] Also, the mean improvement in VA was comparable after 2 years.[1] Brolucizumab was shown in the HAWK and HARRIER trials to be noninferior to aflibercept in terms of visual acuity outcomes with comparatively better anatomical outcomes.[4] They did not, however, assess the differences in therapy responses based on the MNV type. In our case report, we highlight the visual and anatomical responses of type 3 MNV to IVI brolucizumab therapy.

Dell'Omo et al.[8] have shown that the aqueous levels of VEGF are substantially higher in type 3 MNV than in type 1 or 2 MNV in eyes with untreated nAMD. Thus, an anti-VEGF agent with better VEGF-binding capability will potentially be preferred in these cases. Brolucizumab is a humanized single-chain antibody fragment with a molecular weight of only 26 kDa.[9],[10] It initially binds to VEGF-A in a 2:1 ratio due to its smaller size; however, once the drug's concentration is reduced, this ratio may drop to 1:1.[9],[10] Brolucizumab, however, continues to completely block VEGF-A even at a 1:1 ratio.[9],[10] Furthermore, brolucizumab has a low molecular weight, which is four times lower than aflibercept and 1.8 times lower than ranibizumab.[9],[10] This enables it to be delivered at a molar dose that is 22 times higher than ranibizumab and 12 times higher than aflibercept.[9],[10] Brolucizumab has also been demonstrated to have longer durability in numerous trials on nAMD due to these molecular properties.[4],[11],[12] With this background, our patient was offered brolucizumab treatment. The patient demonstrated significant visual and anatomical improvement to a single dose of IVI of brolucizumab. Despite not receiving additional anti-VEGF treatment after 1 month, the patient continued to show visual improvement as well as improved morphology on SD-OCT for up to 3 months. This reinforces the durability of the molecule for extended regimens. Furthermore, while intraocular inflammation (IOI) is still a concern with the brolucizumab molecule,[4] we did not see any ocular or systemic side events in our case during the 3 months.

  Conclusion Top

In conclusion, a single-dose IVI of brolucizumab is efficacious for the treatment of type 3 MNV, with good visual and anatomical outcomes lasting up to 3 months. Nonetheless, further studies with a larger sample size and longer duration are warranted to investigate this further.

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


Conflicts of interest

There are no conflicts of interest.

  References Top

Daniel E, Shaffer J, Ying GS, Grunwald JE, Martin DF, Jaffe GJ, et al. Outcomes in eyes with retinal angiomatous proliferation in the comparison of age-related macular degeneration treatments trials (CATT). Ophthalmology 2016;123:609-16.  Back to cited text no. 1
Tsai ASH, Cheung N, Gan ATL, Jaffe GJ, Sivaprasad S, Wong TY, et al. Retinal angiomatous proliferation. Surv Ophthalmol 2017;62:462-92.  Back to cited text no. 2
Chakraborty S, Sheth JU. Contralateral effect following intravitreal brolucizumab injection in diabetic macular edema. Case Rep Ophthalmol Med 2022;2022:3755249.  Back to cited text no. 3
Dugel PU, Singh RP, Koh A, Ogura Y, Weissgerber G, Gedif K, et al. HAWK, and HARRIER: Ninety-six-week outcomes from the phase 3 trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 2021;128:89-99.  Back to cited text no. 4
Huang YY, Lo WJ, Chang HY, Chou YB, Lin TC. Three-year outcomes of intravitreal aflibercept injections for retinal angiomatous proliferation according to disease stage. Ophthalmol Ther 2022;11:1503-16.  Back to cited text no. 5
Viola F, Massacesi A, Orzalesi N, Ratiglia R, Staurenghi G. Retinal angiomatous proliferation: Natural history and progression of visual loss. Retina 2009;29:732-9.  Back to cited text no. 6
Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, Brown DM, Chong V, Nguyen QD, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: Ninety-six-week results of the VIEW studies. Ophthalmology 2014;121:193-201.  Back to cited text no. 7
Dell'Omo R, Cassetta M, dell'Omo E, di Salvatore A, Hughes JM, Aceto F, et al. Aqueous humor levels of vascular endothelial growth factor before and after intravitreal bevacizumab in type 3 versus type 1 and 2 neovascularization. A prospective, case-control study. Am J Ophthalmol 2012;153:155-61.e2.  Back to cited text no. 8
Tadayoni R, Sararols L, Weissgerber G, Verma R, Clemens A, Holz FG. Brolucizumab: A newly developed anti-vegf molecule for the treatment of neovascular age-related macular degeneration. Ophthalmologica 2021;244:93-101.  Back to cited text no. 9
Chakraborty D, Sheth JU, Boral S, Sinha TK. Off-label intravitreal brolucizumab for recalcitrant diabetic macular edema: A real-world case series. Am J Ophthalmol Case Rep 2021;24:101197.  Back to cited text no. 10
Holz FG, Dugel PU, Weissgerber G, Hamilton R, Silva R, Bandello F, et al. Single-chain antibody fragment VEGF inhibitor RTH258 for neovascular age-related macular degeneration: A randomized controlled study. Ophthalmology 2016;123:1080-19.  Back to cited text no. 11
Dugel PU, Jaffe GJ, Sallstig P, Warburton J, Weichselberger A, Wieland M, et al. Brolucizumab versus aflibercept in participants with neovascular age-related macular degeneration: A randomized trial. Ophthalmology 2017;124:1296-304.  Back to cited text no. 12


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