A case of choroidal neovascular membrane in Best vitelliform macular dystrophy treated with intravitreal brolucizumab

Pradeep K Panigrahi; Yamijala Neha Srija; Japesh Thareja; Jasmita Satapathy; Anita Minj

doi:10.4103/IJO.IJO_2534_22

CASE REPORT

Year : 2023 | Volume : 3 | Issue : 2 | Page : 436-438

A case of choroidal neovascular membrane in Best vitelliform macular dystrophy treated with intravitreal brolucizumab

Pradeep K Panigrahi, Yamijala Neha Srija, Japesh Thareja, Jasmita Satapathy, Anita Minj
Department of Ophthalmology, Institute of Medical Sciences and SUM Hospital, Siksha O Anusandhan (Deemed to be) University, Bhubaneswar, Odisha, India

Date of Submission	02-Oct-2022
Date of Acceptance	15-Dec-2022
Date of Web Publication	28-Apr-2023

Correspondence Address:
Pradeep K Panigrahi
Department of Ophthalmology, Institute of Medical Sciences and SUM Hospital, Siksha O Anusandhan (Deemed to be) University, 8-Kalinga Nagar, Bhubaneswar - 751 003, Odisha
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJO.IJO_2534_22

Abstract

A 21-year-old healthy male presented with loss of vision associated with metamorphopsia in the right eye of 6 weeks duration. The patient was a known case of best vitelliform macular dystrophy in both eyes. Clinical and imaging studies lead to a diagnosis of the choroidal neovascular membrane (CNVM). The diseased eye was treated with a single dose of intravitreal brolucizumab. Significant gains in visual acuity and reduction in the subretinal fluid were noted over 2 months of follow-up. Intravitreal brolucizumab can be an effective option in treating CNVMs associated with macular dystrophy.

Keywords: Best dystrophy, brolucizumab, choroidal neovascular membrane, intravitreal, vitelliform

How to cite this article:
Panigrahi PK, Srija YN, Thareja J, Satapathy J, Minj A. A case of choroidal neovascular membrane in Best vitelliform macular dystrophy treated with intravitreal brolucizumab. Indian J Ophthalmol Case Rep 2023;3:436-8

How to cite this URL:
Panigrahi PK, Srija YN, Thareja J, Satapathy J, Minj A. A case of choroidal neovascular membrane in Best vitelliform macular dystrophy treated with intravitreal brolucizumab. Indian J Ophthalmol Case Rep [serial online] 2023 [cited 2023 Jun 5];3:436-8. Available from: https://www.ijoreports.in/text.asp?2023/3/2/436/374952

Best vitelliform macular dystrophy (BVMD) is an inherited disorder associated with a mutation in the gene encoding for the bestrophin protein, which is an ion channel protein in the retinal pigment epithelium (RPE).^[1] It is clinically characterized by the bilateral accumulation of subretinal yellowish material in the macular area, which can lead to decreased vision as the disease progresses. Five different stages of the disease have been identified, which are the previtelliform, vitelliform, pseudohypopyon, vitelliruptive, and atrophic stages. BVMD can sometimes be complicated with a choroidal neovascular membrane (CNVM).^[2] CNVM is a serious complication seen in 20% of cases of BVMD.^[1]

We report a case of CNVM in a patient with BVMD, which was successfully treated with a single dose of intravitreal brolucizumab.

Case Report

A 21-year-old healthy male presented with decreased vision in the right eye (RE) associated with distortion for the last 6 weeks. The patient was a known case of BVMD and had been diagnosed with CNVM in RE elsewhere. He had come to us for a second opinion. Best corrected visual acuity (BCVA) in RE was 20/80, N18 and 20/20, N6 in the left eye (LE). Anterior segment examination was unremarkable bilaterally. Intraocular pressure measured using Goldmann's applanation tonometer was 17 and 16 mm of Hg in RE and LE, respectively. Fundus examination of the RE revealed a yellowish hypopigmented lesion with subretinal hemorrhage and subretinal fluid in the macular area [Figure 1]a. A smaller egg yolk-like hypopigmented lesion was noted in the macular area in LE [Figure 1]b. We clinically diagnosed it as a case of BVMD in both eyes with CNVM in the RE.

Figure 1: (a): Color fundus photograph of the right eye showing yellowish hypopigmented lesion in the macular area with subretinal hemorrhage (white arrow). (b): Color fundus photograph of the left eye showing smaller egg yolk-like hypopigmented lesion in the macular area

Click here to view

The patient had undergone a few investigations elsewhere. Fundus fluroescein angiography showed features of classic CNVM in RE. Electrooculogram showed reduced Arden's ratio bilaterally (RE: 1.72, LE: 1.46). Spectral-domain optical coherence tomography (SD-OCT) done at our center showed type 2 CNVM with the subretinal fluid in RE [Figure 2]a. A subretinal vitelliform lesion was noted on SD-OCT in LE [Figure 2]b. Optical coherence tomography angiography could not be done because of nonavailability of the machine at our center.

Figure 2: (a): Spectral-domain optical coherence tomography image of the right eye showing choroidal neovascular membrane (white arrow) with the subretinal fluid (white arrowhead). (b): Spectral-domain optical coherence tomography image of the left eye showing subretinal vitelliform material in the macular area (white arrow)

Click here to view

Management options were discussed with the patient, and the patient was given the option of intravitreal ranibizumab, aflibercept, and brolucizumab. Pros and cons of each agent and the risks associated with the procedure were clearly explained. The patient opted for intravitreal brolucizumab. The patient received a single dose of intravitreal brolucizumab (6 mg/0.05 ml) in his RE under sterile precautions. Postoperatively, the patient was started on topical moxifloxacin (0.5%) 4 times a day for 1 week. Symptoms of any ocular or systemic side effects were explained and the patient was advised to seek immediate medical attention at the onset of any such symptom.

The patient presented 1 month following the intravitreal injection. BCVA in RE had improved to 20/32, N8. Fundus examination showed complete resolution of subretinal hemorrhage with a reduction in the subretinal fluid in OCT [Figure 3]a and [Figure 3]b. Two months following the injection, BCVA had further improved to 20/20 (P), N6. The patient no longer had complaints of metamorphopsia. Fundus examination showed a hypopigmented lesion in the macular area with resolved subretinal hemorrhage [Figure 3]c. OCT examination showed almost complete resolution of subretinal fluid [Figure 3]d. No further injections were planned, and the patient was asked to be on regular follow-up. There were no signs of retinal vasculitis throughout the follow-up period.

Figure 3: (a): Color fundus photograph of the right eye 1 month following injection showing hypopigmented lesion in the macular area with resolution of subretinal hemorrhage. (b): Spectral-domain optical coherence tomography image of the right eye 1 month following injection showing a reduction in the subretinal fluid. (c): Color fundus photograph 2 months following injection showing hypopigmented lesion with complete resolution of subretinal hemorrhage. (d): Spectral-domain optical coherence tomography image of the right eye 2 months following injection showing almost complete resolution of subretinal fluid

Click here to view

Discussion

Brolucizumab is a humanized, single-chain variable fragment that inhibits vascular endothelial growth factor-A (VEGF-A). It is composed of the monoclonal antibody's variable light and heavy chain domains tethered by a flexible linker resulting in a small protein fragment of approximately 26 kDA.^[3] Smaller size results in improved bioavailability and reduced immunogenicity.^[4] Recent clinical trials on age-related macular degeneration (ARMD) have shown that brolucizumab was noninferior to aflibercept in visual function at week 48 with >50% of patients being able to be maintained on three monthly dosing intervals.^[5] Anatomic outcomes like reduction in the subretinal fluid and central subfield retinal thickness favored brolucizumab over aflibercept.

RPE dysfunction associated with BVMD results in the accumulation of fluid in the subretinal space separating the retinal layers from the RPE. This results in reduced phagocytosis of the outer segments of photoreceptors. There occurs an increased accumulation of lipofuscin due to increased oxidative stress, thereby leading to an increase in free radical-mediated retinal damage.^[1] The severity of RPE dysfunction and increase in oxidative stress are believed to initiate the development of CNVM in BVMD.^[6]

CNVM associated with BVMD has been successfully treated with anti-VEGF agents like bevacizumab and ranibizumab.^[1],[2],[7] Most of these cases do not require multiple injections, as is the case of CNVM associated with ARMD. Our case responded well to a single dose of intravitreal brolucizumab. Improvement in vision and reduction in subretinal fluid was maintained till 2 months follow-up. Smaller molecular size resulting in better retinal penetration and higher binding affinity for VEGF A isoforms might be the potential reasons for a single dose of intravitreal brolucizumab performing well in this case.

Conclusion

To the best of our knowledge, this is the first case of CNVM secondary to BVMD successfully treated with intravitreal brolucizumab. Intravitreal brolucizumab adds to the armamentarium available to the retina specialist in managing such cases. However, longer follow-up will be needed to determine the optimum number of intravitreal injections in such cases.

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

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Adiyeke SK, Ture G. Choroidal neovascularization associated with best vitelliform macular dystrophy. Beyoglu Eye J 2022;7:103-8.
2.	Rishi E, Rishi P, Mahajan S. Intravitreal bevacizumab for choroidal neovascular membrane associated with Best's vitelliform dystrophy. Indian J Ophthalmol 2010;58:160-2. [PUBMED] [Full text]
3.	Panigrahi PK. A case of recalcitrant neovascular wet age-related macular degeneration treated with intravitreal brolucizumab. Photodiagnosis Photodyn Ther 2021;35:102450. doi: 10.1016/j.pdpdt. 2021.102450.
4.	Fernandes CFC, Pereira SDS, Luiz MB, Zuliani JP, Furtado GP, Stabeli RG. Camelid single-domain antibodies as an alternative to overcome challenges related to the prevention, detection, and control of neglected tropical diseases. Front Immunol 2017;8:653. doi: 10.3389/fimmu. 2017.00653.
5.	Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, et al. HAWK and HARRIER: Phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 2020;127:72-84.
6.	Alisa-Victoria K, Jin-Poi T, Shatriah I, Zunaina E, Ngah NF. Choroidal neovascularization secondary to Best's vitelliform macular dystrophy in two siblings of a Malay family. Clin Ophthalmol 2014;12:537-42.
7.	Celea C, Pop M, Avidis-Zamfiroiu N, Celea C. Evolution of choroidal neovascular membrane in best disease after single intravitreal bevacizumab. Case report. Maedica (Bucur) 2015;10:61-4.