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 Table of Contents  
Year : 2023  |  Volume : 3  |  Issue : 2  |  Page : 439-440

Spontaneous closure of full-thickness macular hole after intravitreal brolucizumab injection for neovascular age-related macular degeneration

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

Date of Submission08-Aug-2022
Date of Acceptance12-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_1951_22

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The authors describe the first case report of spontaneous closure of full-thickness macular hole (FTMH) in a 74-year-old female patient with macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) after intravitreal injection (IVI) of brolucizumab. A significant improvement in the pigment epithelial detachment (PED) morphology seems to have facilitated the hole closure by relieving the centrifugal traction onto the overlying retina. Another proposed mechanism for hole closure is glial cell proliferation caused by the brolucizumab molecule acting on the underlying MNV. However, more histologic validation is needed to confirm the same.

Keywords: Anti-vascular endothelial growth factor, brolucizumab, full-thickness macular hole, neovascular age-related macular degeneration

How to cite this article:
Chakraborty S, Sheth JU. Spontaneous closure of full-thickness macular hole after intravitreal brolucizumab injection for neovascular age-related macular degeneration. Indian J Ophthalmol Case Rep 2023;3:439-40

How to cite this URL:
Chakraborty S, Sheth JU. Spontaneous closure of full-thickness macular hole after intravitreal brolucizumab injection for neovascular age-related macular degeneration. Indian J Ophthalmol Case Rep [serial online] 2023 [cited 2023 Jun 6];3:439-40. Available from: https://www.ijoreports.in/text.asp?2023/3/2/439/374918

A full-thickness macular hole (FTMH) is a foveal anatomic defect characterized by the interruption of neural retinal layers extending from the internal limiting membrane (ILM) to the retinal pigment epithelium (RPE).[1] It can be either idiopathic or secondary to posterior segment pathologies such as trauma, macular telangiectasia, high myopia, neovascular age-related macular degeneration, and so on.[2] Although the standard of care for FTMH management remains pars plana vitrectomy with ILM peeling, and gas tamponade, its spontaneous closure has been sporadically reported.[3],[4]

Intravitreal therapy with anti-vascular endothelial factor (anti-VEGF) agents is the treatment of choice for macular disorders such as macular neovascularization (MNV) secondary to age-related macular degeneration (AMD).[5] Brolucizumab (Beovu®; Novartis, Basel, Switzerland) was approved by the US Food and Drug Administration (FDA) for use in MNV in 2019.[6]

Although spontaneous closure of FTMH after intravitreal injection (IVI) with bevacizumab and ranibizumab has been documented,[7],[8] a thorough PubMed/Medline search showed that such an occurrence after IVI of brolucizumab is yet to be described.

  Case Report Top

A 74-year-old female presented with diminution of vision in the left eye (OS) for 1 month. Her best-corrected visual acuity (BCVA) was 20/40 in right eye (OD) and 20/80 in OS. Both eyes' (OU) anterior segments were unremarkable. Fundus examination of OD showed changes of dry AMD, while OS demonstrated the presence of a large retinal pigment epithelial detachment (PED) with an overlying FTMH [Figure 1]a. Posterior vitreous detachment (PVD) was clinically noted in OS. On spectral-domain optical-coherence tomography (SD-OCT), a small FTMH having a basal diameter of 391 μm along with the PVD was established in OS [Figure 1]b. Additionally, the large irregular PED with a height of 531 μm was noted [Figure 1]b. Moreover, OS-OCT also showed the presence of intraretinal fluid (IRF) at baseline [Figure 1]b. With a provisional diagnosis of OS MNV with FTMH, the patient underwent three loading doses of IVI brolucizumab.
Figure 1: Serial CFP SD-OCT scans of the left eye (OS). At baseline, OS showed the presence of a large PED (height 531 μm) with a FTMH (basal diameter 391 μm) (a and b), for which the patient received three loading doses of intravitreal brolucizumab injection. At 1 month, there was type 1 closure of the FTMH with a decrease in the PED height (475 μm) and presence of residual IRF and SRF (c and d). Subsequently, at 3 months, the FTMH remained closed (e and f) with a significant reduction in the PED (116 μm), complete resolution of SRF, and presence of trace IRF. CFP = color fundus photographs, FTMH = full-thickness macular hole, IRF = intraretinal fluid, PED = pigment epithelial detachment, SD-OCT = spectral-domain optical coherence tomography, SRF = subretinal fluid

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At 1 month, the OS BCVA improved significantly to 20/50. The PED height improved to 475 μm with spontaneous type 1 closure of the overlying FTMH [Figure 1]d. The SD-OCT showed residual IRF with subretinal fluid (SRF) at this visit, and the patient subsequently underwent administration of the second and third dose of brolucizumab [Figure 1]c. After another 2 months, the BCVA improved to 20/40 in OS. The SD-OCT at this stage illustrated significant reduction in the PED height (116 μm), with complete resolution of SRF and presence of trace IRF [Figure 1]f. The FTMH remained notably closed at this visit too [Figure 1]e. There were no ocular or systemic side effects observed. [Figure 1] illustrates the serial color fundus photographs and SD-OCT images at all visits.

  Discussion Top

MNV is a leading cause of irreversible visual loss worldwide.[9] Long-term sequelae such as recurrent hemorrhage, scarring, persistent fluid, atrophy, and rarely Macular Hole development can result in profound visual loss.[4],[7],[10] Although idiopathic MH development is related to the tangential and anteroposterior vitreous tractional forces,[11] the cause of secondary MH in MNV can be due to factors such as tensile pressure due to an underlying PED, rupture of chronic intraretinal cysts, and/or glial apoptosis.[7],[12] In our case, the presence of a large PED may have resulted in mechanical stretching of the overlying retina, which was already compromised by the presence of fluid, particularly IRF, and the underlying neovascular activity. Raiji et al.[13] have demonstrated successful management of FTMH with PED by pars plana vitrectomy. On the other hand, spontaneous closure of FTMH following anti-VEGF therapy has also been described in the literature.[4],[7],[8] Sethia et al.[4] described a case of spontaneous formation and closure of FTMH with bevacizumab therapy in a patient with polypoidal choroidal vasculopathy (PCV) with an underlying PED. Storch and Hoerauf[7] reported a similar case of MH closure after intravitreal bevacizumab injection for MNV with a large PED. However, the occurrence of such a phenomenon after brolucizumab injection has not been published in the literature.

The existence of a large PED in our case may have influenced the intraoperative surgical maneuver and, as a result, the final surgical outcome. Additionally, the patient had reasonably good baseline visual acuity (20/80) with a small MH. Due to these factors, surgical intervention was withheld and the patient was treated with three loading doses of anti-VEGF therapy. Following a single dose of injection, there was complete closure of the MH that was preserved till 3 months of follow-up. A notable reduction in the PED height appeared to have relieved the centrifugal drag onto the overlying retina. This could allow the MH edges to be approximated together and the hole to be closed, as illustrated on the follow-up OCT. Another possible mechanism for the hole closure could be the glial tissue proliferation secondary to the underlying exudative disease. Treatment with an anti-VEGF injection can promote healing of the diseased tissue and secondary gliosis, thereby promoting hole closure.

At 96 weeks, the HAWK and HARRIER trials demonstrated that IVI brolucizumab was not inferior to aflibercept in terms of visual outcomes.[14] Moreover, when compared to aflibercept, brolucizumab demonstrated better fluid resolution.[14] With this backdrop, our patient was offered treatment with the brolucizumab molecule. The patient demonstrated excellent anatomical response to three loading doses of brolucizumab with a near-total resolution of the fluid and significant reduction in the PED. Simultaneously, the MH closed too with notable visual improvement at 3 months. The occurrence of episodes of intraocular inflammation (IOI) remains a concern with the brolucizumab molecule, which was reported in 4% of eyes of the HAWK and HARRIER trials.[14] However, we did not observe any signs of IOI after the three injections. Additionally, no other ocular or systemic adverse events were noted.

  Conclusion Top

In conclusion, this is the first reported case of spontaneous closure of FTMH after IVI of brolucizumab. The improvement in PED morphology secondary to brolucizumab therapy appears to have relieved the mechanical stress, thereby facilitating the approximation and spontaneous closure of the macular hole. Glial cell proliferation can be another putative mechanism for the hole closure, which needs to be further corroborated by histologic studies.

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

Duker JS, Kaiser PK, Binder S, de Smet MD, Gaudric A, Reichel E, et al. The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology 2013;120:2611-9.  Back to cited text no. 1
Kang HG, Han JY, Choi EY, Byeon SH, Kim SS, Koh HJ, et al. Clinical characteristics, risk factors, and surgical outcomes of secondary macular hole after vitrectomy. Sci Rep 2019;9:19535.  Back to cited text no. 2
Lee J, Nguyen VQ, Doss MK, Eller AW. Spontaneous closure of a chronic full thickness macular hole after failed surgery. Am J Ophthalmol Case Rep 2018;13:59-61.  Back to cited text no. 3
Sethia A, Sheth J, Gopalakrishnan M, Anantharaman G. Spontaneous formation and closure of full thickness macular hole after treatment with anti-vascular endothelial growth factor therapy in polypoidal choroidal vasculopathy. Indian J Ophthalmol 2019;67:1756-8.  Back to cited text no. 4
[PUBMED]  [Full text]  
Yorston D. Anti-VEGF drugs in the prevention of blindness. Community Eye Health 2014;27:44-6.  Back to cited text no. 5
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. 6
Storch MW, Hoerauf H. Case report of a secondary macular hole closure after intravitreal bevacizumab therapy in a patient with retinal pigment epithelial detachment. Indian J Ophthalmol 2017;65:632-3.  Back to cited text no. 7
[PUBMED]  [Full text]  
Goel N. Full thickness macular hole formation and spontaneous closure during intravitreal Ranibizumab therapy for central retinal vein occlusion. Retin Cases Brief Rep 2022;16:678-80.  Back to cited text no. 8
Stewart MW. Clinical and differential utility of VEGF inhibitors in wet age-related macular degeneration: Focus on aflibercept. Clin Ophthalmol 2012;6:1175-86.  Back to cited text no. 9
Nguyen V, Barthelmes D, Gillies MC. Neovascular age-related macular degeneration: A review of findings from the real-world Fight Retinal Blindness! registry. Clin Exp Ophthalmol 2021;49:652-63.  Back to cited text no. 10
Johnson MW. Posterior vitreous detachment: Evolution and role in macular disease. Retina 2012;32(Suppl 2):S174-8.  Back to cited text no. 11
Brüggemann A, Hoerauf H. Atypische Makulaforamina nicht idiopathischer Genese [Atypical macular holes]. Klin Monbl Augenheilkd 2008;225:281-5.  Back to cited text no. 12
Raiji VR, Eliott D, Sadda SR. Macular hole overlying pigment epithelial detachment after intravitreal injection with ranibizumab. Retin Cases Brief Rep 2013;7:91-4.  Back to cited text no. 13
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. 14


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