Skip to main content

Advertisement

SpringerLink
Log in

Dexamethasone implant improves anatomic response to anti-VEGF therapy in treatment-resistant polypoidal choroidal vasculopathy

  • Original Paper
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Background

A significant proportion of eyes with polypoidal choroidal vasculopathy (PCV) can be resistant to anti-vascular endothelial growth factor (VEGF) injections. We evaluated the efficacy of a combination of dexamethasone intravitreal implant (DXI) and anti-VEGF therapy in eyes resistant to anti-VEGF monotherapy.

Methods

In this retrospective study, patients with PCV resistant to anti-VEGF injections were additionally injected with a DXI along with an anti-VEGF agent. Best-corrected visual acuity (BCVA), slit-lamp examination, fundus evaluation, and optical coherence tomography (OCT) data were analyzed. Anatomical response on OCT was the primary outcome measure. Change in visual acuity and injection-free interval after DXI were evaluated as secondary outcome measures.

Results

Twelve eyes of 11 patients were included in the study. Mean age of patients at presentation was 64.7 ± 9.5 years (range, 49–78.8 years), and there were seven females (63.6%). Median number of anti-VEGF injections prior to DXI was 4 (interquartile range IQR, 3–7). Median follow-up duration after DXI was 32.2 months (IQR, 6.6–41.6 months). Median logMAR BCVA immediately prior to DXI was 0.41 (IQR, 0.30–0.88) and after injection was 0.40 (IQR, 0.30–1.05), which was not significantly different (p = 0.85). Median Central Retinal Thickness (CRT) after DXI was 305.5 µm (IQR, 249–409 µm), which was significantly (p = 0.003) lesser than pre-injection thickness of 547 µm (IQR, 431–771 µm). Median injection-free interval in these eyes after DXI was 5 months (IQR, 2.8–6.4 months). Kaplan–Meier estimates of first injection after DXI were 27.3% at 3 months, 67.3% at 6 months, and 89.1% at 12 months.

Conclusions

Dexamethasone implant combined with anti-VEGF treatment can prolong the treatment-free interval in eyes with PCV resistant to anti-VEGF injection while maintaining visual acuity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

BCVA:

Best-corrected visual acuity

CNVM:

Choroidal neovascular membrane

CRT:

Central retinal thickness

DXI:

Dexamethasone implant

FFA:

Fundus fluorescein angiography

ICGA:

Indocyanine green angiography

IOP:

Intraocular pressure

IQR:

Inter-quartile range

ME:

Macular edema

nAMD:

Neovascular age-related macular degeneration

PCV:

Polypoidal choroidal vasculopathy

PED:

Pigment epithelial detachment

OCT:

Optical coherence tomography

VEGF:

Vascular endothelial growth factor

References

  1. Koh A, Lee WK, Chen LJ, Chen SJ, Hashad Y, Kim H et al (2012) EVEREST study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina 32(8):1453–1464

    Article  CAS  Google Scholar 

  2. Lee WK, Iida T, Ogura Y, Chen SJ, Wong TY, Mitchell P et al (2018) Efficacy and Safety of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in the PLANET Study: A Randomized Clinical Trial. JAMA Ophthalmol 136(7):786–793

    Article  Google Scholar 

  3. Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE et al (2012) Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology 119:1388–1398

    Article  Google Scholar 

  4. Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD et al (2012) Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548

    Article  Google Scholar 

  5. Lux A, Llacer H, Heussen FM, Joussen AM (2007) Non-responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions. Br J Ophthalmol 91:1318–1322

    Article  Google Scholar 

  6. Krebs I, Glittenberg C, Ansari-Shahrezaei S, Hagen S, Steiner I, Binder S (2013) Non-responders to treatment with antagonists of vascular endothelial growth factor in age-related macular degeneration. Br J Ophthalmol 97:1443–1446

    Article  Google Scholar 

  7. Suzuki M, Nagai N, Izumi-Nagai K, Shinoda H, Koto T, Uchida A et al (2014) Predictive factors for non-response to intravitreal ranibizumab treatment in age-related macular degeneration. Br J Ophthalmol 98:1186–1191

    Article  Google Scholar 

  8. Kokame GT, deCarlo TE, Kaneko KN, Omizo JN, Lian R (2019) Anti-Vascular endothelial growth factor resistance in exudative macular degeneration and polypoidal choroidal vasculopathy. Ophthalmology Retina 3:744–752

    Article  Google Scholar 

  9. Yang S, Zhao J, Sun X (2016) Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review. Drug Des Dev Ther 10:1857

    Article  CAS  Google Scholar 

  10. Agrawal R, Balne PK, Wei X, Bijin VA, Lee B, Ghosh A et al (2019) Cytokine profiling in patients with exudative age-related macular degeneration and polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci 60(1):376–382

    Article  CAS  Google Scholar 

  11. Kuppermann BD, Goldstein M, Maturi RK, Pollack A, Singer M, Tufail A et al (2015) Dexamethasone intravitreal implant as adjunctive therapy to ranibizumab in neovascular age-related macular degeneration: a multicenter randomized controlled trial. Ophthalmologica 234:40–54

    Article  CAS  Google Scholar 

  12. Ranchod TM, Ray SK, Daniels SA, Leong CJ, Ting TD, Verne AZ (2013) LuceDex: a prospective study comparing ranibizumab plus dexamethasone combination therapy versus ranibizumab monotherapy for neovascular age-related macular degeneration. Retina 33(8):1600–1604

    Article  CAS  Google Scholar 

  13. Calvo P, Ferreras A, Al Adel F, Wang Y, Brent MH (2015) Dexamethasone intravitreal implant as adjunct therapy for patients with wet age-related macular degeneration with incomplete response to ranibizumab. Br J Ophthalmol 99:723–726

    Article  Google Scholar 

  14. Rezar-Dreindl S, Eibenberger K, Buehl W, Georgopoulos M, Weigert G, Krall C et al (2017) Role of additional dexamethasone for the management of persistent or recurrent neovascular age-related macular degeneration under ranibizumab treatment. Retina 37:962–970

    Article  CAS  Google Scholar 

  15. Todorich B, Thanos A, Yonekawa Y, Mane G, Hasbrook M, Thomas BJ et al (2017) Simultaneous dexamethasone intravitreal implant and anti-vegf therapy for neovascular age-related macular degeneration resistant to anti-vegf monotherapy. J Vitreoret Dis 1:65–74

    Article  Google Scholar 

  16. Giancipoli E, Pinna A, Boscia F, Zasa G, Sotgiu G, Dore S et al (2018) Intravitreal dexamethasone in patients with wet age-related macular degeneration resistant to anti-vegf: A prospective pilot study. J Ophthalmol 2018:1–8

    Article  Google Scholar 

  17. Jonas JB, Libondi T, Golubkina L, Spandau UH, Schlichtenbrede F, Rensch F (2010) Combined intravitreal bevacizumab and triamcinolone in exudative age-related macular degeneration. Acta Ophthalmol 88:630–634

    Article  CAS  Google Scholar 

  18. Tozer K, Roller AB, Chong LP, Sadda S, Folk JC, Mahajan VB et al (2013) Combination therapy for neovascular age-related macular degeneration refractory to anti-vascular endothelial growth factor agents. Ophthalmology 120:2029–2034

    Article  Google Scholar 

  19. Veritti D, Sarao V, Lanzetta P (2013) Bevacizumab and triamcinolone acetonide for choroidal neovascularization due to age-related macular degeneration unresponsive to antivascular endothelial growth factors. J Ocul Pharmacol Ther 29:437–441

    Article  CAS  Google Scholar 

  20. Kauppinen A, Paterno JJ, Blasiak J, Salminen A, Kaarniranta K (2016) Inflammation and its role in age-related macular degeneration. Cell Mol Life Sci 73:1765–1786

    Article  CAS  Google Scholar 

  21. Kauppinen A, Niskanen H, Suuronen T, Kinnunen K, Salminen A, Kaarniranta K (2012) Oxidative stress activates NLRP3 inflammasomes in ARPE-19 cells—implications for age-related macular degeneration (AMD). Immunol Lett 147:29–33

    Article  CAS  Google Scholar 

  22. Nozaki M, Raisler BJ, Sakurai E, Sarma JV, Barnum SR, Lambris JD et al (2006) Drusen complement components C3a and C5a promote choroidal neovascularization. Proc Natl Acad Sci 103:2328–2333

    Article  CAS  Google Scholar 

  23. Machalińska A, Dziedziejko V, Mozolewska-Piotrowska K, Karczewicz D, Wiszniewska B, Machaliński B (2009) Elevated plasma levels of C3a complement compound in the exudative form of age-related macular degeneration. Ophthalmic Res 42:54–59

    Article  Google Scholar 

  24. Oliver A, Ciulla TA (2006) Corticosteroids as antiangiogenic agents. Ophthalmol Clin North Am 19:345–351

    PubMed  Google Scholar 

  25. Oh H, Takagi H, Takagi C, Suzuma K, Otani A, Ishida K et al (1999) The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes. Invest Ophthalmol Vis Sci 40:1891–1898

    CAS  PubMed  Google Scholar 

  26. Schaal S, Kaplan HJ, Tezel TH (2008) Is there tachyphylaxis to intravitreal anti-vascular endothelial growth factor pharmacotherapy in age-related macular degeneration? Ophthalmology 115:2199–2205

    Article  Google Scholar 

  27. Kwak HW, D’Amico DJ (1992) Evaluation of the retinal toxicity and pharmacokinetics of dexamethasone after intravitreal injection. Arch Ophthalmol 110:259–266

    Article  CAS  Google Scholar 

  28. Chang-Lin JE, Attar M, Acheampong AA, Robinson MR, Whitcup SM, Kuppermann BD et al (2011) Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant. Invest Ophthalmol Vis Sci 52:80–86

    Article  CAS  Google Scholar 

  29. van Wijngaarden P, Coster DJ, Williams KA (2005) Inhibitors of ocular neovascularization: promises and potential problems. JAMA 293:1509–1513

    Article  Google Scholar 

Download references

Acknowledgements

Hyderabad Eye Research Foundation and India Alliance DB Wellcome Trust.

Funding

None.

Author information

Authors and Affiliations

  1. Washington University School of Medicine, St. Louis, MO, USA

    Kushanth Mallikarjun & Rajendra S. Apte

  2. Smt. Kanuri Santhamma Centre for Vitreoretinal Diseases, Suven Clinical Research Centre, IHOPE Centre, L V Prasad Eye Institute, Hyderabad, India

    Raja Narayanan

  3. Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, India

    Rajiv Raman

  4. Ophthalmic Biophysics, L V Prasad Eye Institute, Hyderabad, India

    Ashik Mohamed

  5. Sankara Eye Hospitals, Bengaluru, India

    Mahesh P. Shanmugam

  6. Vitreoretinal Diseases, L V Prasad Eye Institute, Bhubaneswar, India

    Srikant Kumar Padhy

Authors
  1. Kushanth Mallikarjun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raja Narayanan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rajiv Raman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ashik Mohamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mahesh P. Shanmugam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rajendra S. Apte
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Srikant Kumar Padhy
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RN, KM, and AM contributed to data collection, analysis and interpretation, preparation of the manuscript, and provided major revisions to the manuscript. RR, MPS, RSA, and SKP contributed to interpretation and final analysis of manuscript. AM and KM performed statistical analysis. All authors participated in the development and writing of the manuscript and approved the final article for publication.

Corresponding author

Correspondence to Raja Narayanan.

Ethics declarations

Conflict of interest

None of the authors have any competing interests.

Data availability and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on request.

Ethical approval

The study protocol adhered to the tenets of the Declaration of Helsinki and was approved by the local Institutional Review Board (LEC 05–18-089) at L.V. Prasad Eye Institute. All study participants gave a written informed consent before enrollment. Patients were recruited from March 2017 through November 2019.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mallikarjun, K., Narayanan, R., Raman, R. et al. Dexamethasone implant improves anatomic response to anti-VEGF therapy in treatment-resistant polypoidal choroidal vasculopathy. Int Ophthalmol 42, 1263–1272 (2022). https://doi.org/10.1007/s10792-021-02113-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-021-02113-4

Keywords

Search

Navigation