Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Comparison of subretinal aflibercept vs ranibizumab vs bevacizumab in the context of PPV, pneumatic displacement with subretinal air and subretinal tPA in naïve submacular haemorrhage secondary to nAMD. “The Submarine Study”

Eye volume 38, pages 292–296 (2024)Cite this article

Subjects

Abstract

Objective

To compare efficacy and safety profile of subretinal aflibercept, ranibizumab, and bevacizumab in the context of pars plana vitrectomy, pneumatic displacement with subretinal air and subretinal tPA for subretinal macular haemorrhage (SMH) due to naïve neovascular age-related macular degeneration (nAMD).

Design

Retrospective interventional cohort study.

Participants

123 eyes of 123 patients treated with subretinal aflibercept (n = 41, 33%), ranibizumab (n = 41,33%), and bevacizumab (n = 41, 33%).

Methods

Review of electronic medical records for best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) at baseline and 24 months after treatment.

Main outcome measures

BCVA, CST, and number of intravitreal anti VEGF over 24 months.

Results

Mean age of patients was 80.5 ± 5.5 years, 43.9% were female. Mean time from symptom onset until surgery was 1.1 days (range 0–3 days). In all cases, the SMH did not reach the arcades. CST at baseline was 627 ± 140 µ, 739 ± 54 µ, and 793 ± 93 µ (p = 0.0001) for aflibercept, ranibizumab, or bevacizumab, respectively. Baseline BCVA (logMAR) was 0.65 ± 0.13, 0.69 ± 0.96, and 0.74 ± 0.81 (p = 0.0041) for aflibercept, ranibizumab, and bevacizumab, respectively. All three groups showed statistically significant improvement in BCVA and CST (for all groups: p < 0.001). There was no statistically significant difference at the final BCVA (p = 0.789). The mean number of anti VEGF given during follow-up period was 5.2 ± 0.81, 4.4 ± 0.63, and 5.5 ± 0.95 (p = 0.0001) for aflibercept, ranibizumab, and bevacizumab, respectively.

Conclusion

This study shows that aflibercept, ranibizumab, and bevacizumab in a subretinal manner in the context of PPV, pneumatic displacement with subretinal air and subretinal tPA for subretinal macular haemorrhage secondary to naïve nAMD work with the same efficacy and safety profile.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Intraoperative pictures showing the subretinal technique.
Fig. 2: Central macular thickness.
Fig. 3: Best-corrected visual acuity.
Fig. 4: Number of Anti-VEGF injections over the follow-up period.

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this paper or its supplementary material files. Further enquiries can be directed to the corresponding author.

References

  1. Toth CA, Morse LS, Hjelmeland LM, Landers MB. Fibrin directs early retinal damage after experimental subretinal hemorrhage. Arch Ophthalmol (Chic, Ill 1960). 1991;109:723–9.

    Article  CAS  Google Scholar 

  2. Scupola A, Coscas G, Soubrane G, Balestrazzi E. Natural history of macular subretinal hemorrhage in age-related macular degeneration. Ophthalmologica. 1999;213:97–102.

    Article  CAS  PubMed  Google Scholar 

  3. Glatt H, Machemer R. Experimental subretinal hemorrhage in rabbits. Am J Ophthalmol. 1982;94:762–73.

    Article  CAS  PubMed  Google Scholar 

  4. Haupert CL, McCuen BW 2nd, Jaffe GJ, Steuer ER, Cox TA, Toth CA, et al. Pars plana vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-gas exchange for displacement of thick submacular hemorrhage in age-related macular degeneration. Am J Ophthalmol 2001;131:208–15.

    Article  CAS  PubMed  Google Scholar 

  5. Olivier S, Chow DR, Packo KH, MacCumber MW, Awh CC. Subretinal recombinant tissue plasminogen activator injection and pneumatic displacement of thick submacular hemorrhage in Age-Related macular degeneration. Ophthalmology 2004;111:1201–8.

    Article  PubMed  Google Scholar 

  6. Martel JN, Mahmoud TH. Subretinal pneumatic displacement of subretinal hemorrhage. JAMA Ophthalmol. 2013;131:1632–5.

    Article  PubMed  Google Scholar 

  7. Chang W, Garg SJ, Maturi R, Hsu J, Sivalingam A, Gupta SA, et al. Management of thick submacular hemorrhage with subretinal tissue plasminogen activator and pneumatic displacement for age-related macular degeneration. Am J Ophthalmol. 2014;157:1250–7.

    Article  CAS  PubMed  Google Scholar 

  8. Stopa M, Lincoff A, Lincoff H. Analysis of forces acting upon submacular hemorrhage in pneumatic displacement. Retina 2007;27:370–4.

    Article  PubMed  Google Scholar 

  9. Iglicki M, Khoury M, Melamud JI, Donato L, Barak A, Quispe DJ, et al. Naïve subretinal haemorrhage due to neovascular age-related macular degeneration. pneumatic displacement, subretinal air, and tissue plasminogen activator: subretinal vs intravitreal aflibercept-the native study. Eye (Lond). 2023;37:1659–64.

  10. Klettner A, Grotelüschen S, Treumer F, Roider J, Hillenkamp J. Compatibility of recombinant tissue plasminogen activator (rtPA) and aflibercept or ranibizumab coapplied for neovascular age-related macular degeneration with submacular haemorrhage. Br J Ophthalmol. 2015;99:864–9.

    Article  PubMed  Google Scholar 

  11. Avci R, Kapran Z, Ozdek Ş, Teke MY, Oz O, Guven D, et al. Multicenter study of pars plana vitrectomy for optic disc pit maculopathy: MACPIT study. Eye 2017;31:1266–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. The CATT Research Group, The CRG. Ranibizumab and bevacizumab for neovascular. N Engl J Med. 2011;364:1897–908.

    Article  Google Scholar 

  13. Matsuoka M, Ogata N, Otsuji T, Nishimura T, Takahashi K, Matsumura M. Expression of pigment epithelium derived factor and vascular endothelial growth factor in choroidal neovascular membranes and polypoidal choroidal vasculopathy. Br J Ophthalmol. 2004;88:809–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jackson TL, Bunce C, Desai R, Hillenkamp J, Lee CN, Lois N, et al. Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER): study protocol for a phase 3, pan-European, two-group, non-commercial, active-control, ob. Trials 2022;23:99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lüke M, Januschowski K, Warga M, Beutel J, Leitritz M, Gelisken F, et al. The retinal tolerance to bevacizumab in co-application with a recombinant tissue plasminogen activator. Br J Ophthalmol. 2007;91:1077–82.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Singh RP, Patel C, Sears JE. Management of subretinal macular haemorrhage by direct administration of tissue plasminogen activator. Br J Ophthalmol. 2006;90:429–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. de Silva SR, Bindra MS. Early treatment of acute submacular haemorrhage secondary to wet AMD using intravitreal tissue plasminogen activator, C3F8, and an anti-VEGF agent. Eye (Lond). 2016;30:952–7.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Anat Loewenstein and Dinah Zur, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Author information

Authors and Affiliations

  1. Private Retina Office, University of Buenos Aires, Buenos Aires, Argentina

    Matias Iglicki

  2. Medical Investigation Institute “Alfredo Lanari”, University of Buenos Aires, Buenos Aires, Argentina

    Marina Khoury & Javier Ignacio Melamud

  3. Ophthalmologic Institute, Buenos Aires, Argentina

    Lucas Donato

  4. Diagnostic Ophthalmology Center, Buenos Aires, Argentina

    Diego Jose Quispe & Hermino Pablo Negri

Authors
  1. Matias Iglicki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marina Khoury
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucas Donato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Diego Jose Quispe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hermino Pablo Negri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Javier Ignacio Melamud
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MI, DJQ, MK. - Substantial contributions to the conception or design of the work; the acquisition, analysis, and interpretation of data for the work. - Drafting the work or revising it critically for important intellectual content. - Final approval of the version to be published. - Ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. JIM, LD, HPN - Substantial contributions to the conception or design of the work and interpretation of data for the work. - Drafting the work or revising it critically for important intellectual content. - Final approval of the version to be published. - Ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Matias Iglicki.

Ethics declarations

Competing interests

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submit- ted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Ethics approval

As this was a retrospective study, participants' informed consent was not needed, in compliance with the Institutional review board (IRB) approval. This study protocol was reviewed and approved by the local IRB. The research adhered to the tenets of the Declaration of Helsinki.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Iglicki, M., Khoury, M., Donato, L. et al. Comparison of subretinal aflibercept vs ranibizumab vs bevacizumab in the context of PPV, pneumatic displacement with subretinal air and subretinal tPA in naïve submacular haemorrhage secondary to nAMD. “The Submarine Study”. Eye 38, 292–296 (2024). https://doi.org/10.1038/s41433-023-02676-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41433-023-02676-9

This article is cited by

Search

Advanced search

Quick links