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Subretinal transient hyporeflectivity in neovascular age-related macular degeneration and its response to a loading phase of aflibercept: PRECISE report 4

Eye (2024)Cite this article

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Abstract

Purpose

To describe the prevalence of subretinal transient hyporeflectivity (STHR) in exudative neovascular age-related macular degeneration (nAMD) and its response to a loading phase of aflibercept.

Methods

Optical coherence tomography (OCT) scans of treatment-naïve nAMD patients captured at baseline and after a loading phase of aflibercept were graded for presence of STHR, defined as a small, well-defined, round, subretinal, hyporeflective area, delimited between the ellipsoid zone (EZ) and the retinal pigmented epithelium/Bruch membrane complex. OCT parameters recorded were macular neovascularisation (MNV) subtypes, location of retinal fluids (subretinal fluid, SRF and intraretinal fluid, IRF), central retinal and choroidal thickness. Response was defined as absence of IRF and SRF. Factors associated with completely resolved STHR versus persistent STHR post-loading phase were compared.

Results

2039 eyes of 1901 patients were analysed. STHR was observed in 79 eyes of 78 patients, with an estimated prevalence of 3.87% (95% CI 3.08–4.81%). STHR were seen in 44 type 1 MNV (56%), 27 with type 2 (34%), and 8 with type 3 (10%). At baseline, a total of 303 STHR were present, ranging between 1–22 per eye. The total number of STHR reduced significantly after the loading phase to 173 (p = 0.002). Complete disappearance of STHR was seen in 44 eyes (56%) and persistent STHR in the rest (44%).

Conclusions

STHR may represent a marker of low-grade exudation in nAMD eyes with good response to a loading phase of aflibercept. However, its potential role as an independent nAMD activity biomarker is limited as most resolve after the loading phase.

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Fig. 1: STHR associated with different MNV types.
Fig. 2: STHR response to aflibercept.
Fig. 3: Recurrence of STHR after a loading phase of aflibercept.
Fig. 4: Choroidal hypertransmission and differential diagnosis.

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Data availability

The dataset generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The research was funded by Boehringer Ingelheim and supported by the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, UCL Institute of Ophthalmology and the NIHR Moorfields Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Funding

Boehringer Ingelheim, Binger Str. 173, 55216, Ingelheim am, Rhein, Germany.

Author information

Authors and Affiliations

  1. NIHR Moorfields Biomedical Research Centre and Clinical Research Facility, Moorfields Eye Hospital NHS Foundation Trust, London, UK

    Andrea Montesel, Raheeba Pakeer Muhammed, Swati Chandak, Dimitrios Kazantzis, Sridevi Thottarath, Shruti Chandra & Sobha Sivaprasad

  2. Institute of Ophthalmology, University College London, London, UK

    Shruti Chandra, Victor Chong & Sobha Sivaprasad

  3. James Paget University Hospitals NHS Foundation Trust, Norfolk, UK

    Benjamin J. L. Burton

  4. Frimley Health NHS Foundation Trust, Surrey, UK

    Geeta Menon

  5. Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK

    Ian Pearce

  6. Leeds Teaching Hospitals NHS Trust, Leeds, UK

    Martin McKibbin

  7. South Tyneside and Sunderland NHS Foundation Trust, Sunderland, UK

    Ajay Kotagiri

  8. Newcastle Hospitals NHS Foundation Trust, Newcastle, UK

    James Talks

  9. King’s College Hospital NHS Foundation Trust, London, UK

    Anna Grabowska

  10. Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK

    Faruque Ghanchi

  11. York Teaching Hospital NHS Foundation Trust, York, UK

    Richard Gale

  12. Boehringer Ingelheim, Rhein, Germany

    Andrea Giani & Taffeta Ching Ning Yamaguchi

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  1. Andrea Montesel
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Contributions

AM and SS designed the study, analysed data, and drafted the manuscript. AM, RPM, DK, SC, ST, and SC collected the data. AM, VC, BJLB, GM, IP, MM, AK, JT, AG, FG, RG, AG, TCNY and SS reviewed the paper and contributed to the final version of the manuscript. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Sobha Sivaprasad.

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Competing interests

None related to the paper. AM, RPM, SC, DK, and ST have no financial disclosures. ShC is a member of the Editorial board. SS received consultancy fees from Bayer, Allergan, Novartis Pharma AG, Roche, Boehringer Ingelheim, Optos, Apellis, Oxurion, Oculis and Heidelberg Engineering and is a member of the Eye editorial board. VC is an employee of Janssen R&D and previously of Boehringer Ingelheim. AG is an employee of Boehringer Ingelheim. TCNY is an employee of Boehringer Ingelheim. BB is in the advisory board and received international conference attendance sponsored by Novartis and Bayer. GM has conducted consultancy-advisory boards for Novartis, Bayer and Allergan, received educational travel grants from Novartis, Bayer, Allergan. IP has received lecture fees from Allergan, Bayer, Heidelberg and Novartis, consultancy fees from Allergan, Alimera, Bayer and Novartis and travel fees from Allergan, Bayer and Novartis. FG has received honorarium for consultancy-advisory boards from Alimera, Allergan, Bayer, Novartis, Oxford BioElectronics, Roche; educational travel grants from Allergan, Bayer, Novartis and is a member of the Eye editorial board. MM has received lecture and advisory board honoraria from Bayer and Novartis and an educational travel grant from Bayer. RG has conducted consultancy-advisory boards for Novartis, Bayer and Allergan, Alimera, Santen, received educational travel grants from Novartis, Bayer, Allergan, Heidelberg Engineering. JT is a consultant for Bayer and Novartis, received grant support from Bayer, Novartis and Heidelberg Engineering, and is involved in research for Allergan, Roche, Bayer, Novartis and Boehringer-Ingelheim. AK received travel support from Novartis, Bayer, and Allergan, and speaker fees from Allergan and Bayer.

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Montesel, A., Pakeer Muhammed, R., Chandak, S. et al. Subretinal transient hyporeflectivity in neovascular age-related macular degeneration and its response to a loading phase of aflibercept: PRECISE report 4. Eye (2024). https://doi.org/10.1038/s41433-024-03087-0

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