Skip to main content

Advertisement

SpringerLink
Log in

Single-session photodynamic therapy combined with intravitreal ranibizumab for neovascular age-related macular degeneration: a comprehensive functional retinal assessment

  • Original Research Article
  • Published:
Documenta Ophthalmologica Aims and scope Submit manuscript

Abstract

Purpose

To explore functional retinal changes in neovascular AMD patients (nAMD) treated with ranibizumab 0.5 mg combined with photodynamic therapy (PDT) 3 days after the first injection in the long term.

Methods

Patients with no prior treatment for nAMD were treated with 3 injections of ranibizumab 0.5 mg 1 month apart and a single session of standard PDT 3 days after the first injection. Best-corrected visual acuity and time-domain OCT at baseline and every 28 ± 2 days were performed; microperimetry at 3, 6, and 12 months and multifocal electroretinogramm (mfERG) at 3 and 12 months were repeated. Fluorescein angiography and vision-related quality-of-life questionnaire were performed at baseline and 12 months.

Results

12/15 nAMD patients completed the 12 months study and received an average of 3.4 ± 0.7 injections. Mean VA changed from 54.67 ± 15.72 to 59.0 ± 24.77 letters (p = 0.371), while mean retinal sensitivity from 5.5 ± 4.8 to 6.6 ± 6.0 dB (p = 0.216). MfERG N1–P1 response amplitude densities (RADs) were significantly different from baseline (p < 0.01) in the central 0°–2.5°, whereas in the peripheral retinal areas (2.5°–20°), not significant (p > 0.01) changes in N1–P1 RADs were detected. The “general vision” VFQ-25 subscale showed a statistically significant improvement at 3 and 12 months.

Conclusions

Ranibizumab 0.5 mg combined with standard PDT 3 days after the first injection determines an improvement of mfERG values in the retinal central area in nAMD patients in long-term follow-up.

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

Similar content being viewed by others

References

  1. Klein R, Klein BE, Jensen SC, Meuer SM (1997) The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 104:7–21

    Article  CAS  PubMed  Google Scholar 

  2. Ferrara N (2000) Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res 55:15–35, discussion 35–36

    CAS  PubMed  Google Scholar 

  3. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY, MARINA Study Group (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431

    Article  CAS  PubMed  Google Scholar 

  4. Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S, ANCHOR Study Group (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444

    Article  CAS  PubMed  Google Scholar 

  5. Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, Shams N (2008) Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol 145:239–248

    Article  CAS  PubMed  Google Scholar 

  6. Bradley J, Ju M, Robinson GS (2007) Combination therapy for the treatment of ocular neovascularization. Angiogenesis 10:141e8

    Article  Google Scholar 

  7. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group (1999) Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP report. Arch Ophthalmol 117:1329–1345

    Article  Google Scholar 

  8. Bressler NM (2001) Treatment of age-related macular degeneration with photodynamic therapy (TAP) study group: photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials—TAP report 2. Arch Ophthalmol 119:198–207

    CAS  PubMed  Google Scholar 

  9. Bressler NM, Arnold J, Benchaboune M, Blumenkranz MS, Fish GE, Gragoudas ES, Lewis H, Schmidt-Erfurth U, Slakter JS, Bressler SB, Manos K, Hao Y, Hayes L, Koester J, Reaves A, Strong HA (2002) Treatment of Age-related macular degeneration with photodynamic therapy (TAP) study group: verteporfin therapy of subfoveal choroidal neovascularization in patients with age-related macular degeneration: additional information regarding baseline lesion composition’s impact on vision outcomes—TAP report no. 3. Arch Ophthalmol 120:1443–1454

    Article  CAS  PubMed  Google Scholar 

  10. Kaiser PK, Brown DM, Zhang K, Hudson HL, Holz FG, Shapiro H, Schneider S, Acharya NR (2007) Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results. Am J Ophthalmol 144:850–857

    Article  CAS  PubMed  Google Scholar 

  11. Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T, ANCHOR Study Group (2009) Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology 116:57–65

    Article  PubMed  Google Scholar 

  12. Schmidt-Erfurth U, Michels S, Barbazetto I, Laqua H (2002) Photodynamic effects on choroidal neovascularization and physiological choroid. Invest Ophthalmol Vis Sci 43:830–841

    PubMed  Google Scholar 

  13. Schmidt-Erfurth U, Schlötzer-Schrehard U, Cursiefen C, Michels S, Beckendorf A, Naumann GO (2003) Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor. Invest Ophthalmol Vis Sci 44:4473–4480

    Article  PubMed  Google Scholar 

  14. Verteporfin in Photodynamic Therapy Study Group (2001) Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization: verteporfin in photodynamic therapy report 2. Am J Ophthalmol 131:541–560

    Article  Google Scholar 

  15. Aiello L, Brucker A, Chang S, Cunningham ET Jr, D’Amico DJ, Flynn HW Jr, Grillone LR, Hutcherson S, Liebmann JM, O’Brien TP, Scott IU, Spaide RF, Ta C, Trese MT (2004) Evolving guidelines for intravitreous injections. Retina 24:S3–S19

    Article  PubMed  Google Scholar 

  16. Ferris FL III, Kassof A, Bresnick GH, Bailey I (1982) New visual acuity charts for clinical research. Am J Ophthalmol 94:91–96

    PubMed  Google Scholar 

  17. Puliafito CA, Hee MR, Lin CP, Reichel E, Schuman JS, Duker JS, Izatt JA, Swanson EA, Fujimoto JG (1995) Imaging of macular diseases with optical coherence tomography. Ophthalmology 102:217–229

    Article  CAS  PubMed  Google Scholar 

  18. Rohrschneider K, Springer C, Bultmann S, Völcker HE (2005) Microperimetry-comparison between the micro perimeter 1 and scanning laser ophthalmoscope-fundus perimetry. Am J Ophthalmol 139:125–134

    Article  PubMed  Google Scholar 

  19. Springer C, Bültmann S, Völcker HE, Rohrschneider K (2005) Fundus perimetry with the micro perimeter 1 in normal individuals: comparison with conventional threshold perimetry. Ophthalmology 112:848–854

    Article  PubMed  Google Scholar 

  20. Fujii GY, de Juan E Jr, Sunness J, Humayun MS, Pieramici DJ, Chang TS (2002) Patient selection for macular translocation surgery using the scanning laser ophthalmoscope. Ophthalmology 109:1737–1744

    Article  PubMed  Google Scholar 

  21. Tanga L, Centofanti M, Oddone F, Parravano M, Parisi V, Ziccardi L, Kroegler B, Perricone R, Manni G (2011) Retinal functional changes measured by frequency-doubling technology in patients treated with hydroxychloroquine. Graefes Arch Clin Exp Ophthalmol 249:715–721

    Article  CAS  PubMed  Google Scholar 

  22. Parisi V, Ziccardi L, Stifano G, Montrone L, Gallinaro G, Falsini B (2010) Impact of regional retinal responses on cortical visually evoked responses: multifocal ERGs and VEPs in the retinitis pigmentosa model. Clin Neurophysiol 121:380–385

    Article  PubMed  Google Scholar 

  23. Parisi V, Tedeschi M, Gallinaro G, Varano M, Saviano S, Piermarocchi S, CARMIS Study Group (2008) Carotenoids and antioxidants in age-related maculopathy Italian study: multifocal electroretinogram modifications after 1 year. Ophthalmology 115(324–333):e2

    PubMed  Google Scholar 

  24. Parisi V, Perillo L, Tedeschi M, Scassa C, Gallinaro G, Capaldo N, Varano M (2007) Macular function in eyes with early age-related macular degeneration with or without contralateral late age-related macular degeneration. Retina 27:879–890

    Article  PubMed  Google Scholar 

  25. Varano M, Parisi V, Tedeschi M, Sciamanna M, Gallinaro G, Capaldo N, Catalano S, Pascarella A (2005) Macular function after PDT in myopic maculopathy: psychophysical and electrophysiological evaluation. Invest Ophthalmol Vis Sci 46:1453–1462

    Article  PubMed  Google Scholar 

  26. Rossi GC, Milano G, Tinelli C (2003) The Italian version of the 25-item National Eye Institute Visual Function Questionnaire: translation, validity, and reliability. J Glaucoma 12:213–220

    Article  PubMed  Google Scholar 

  27. Kaiser PK (2010) Combination therapy with verteporfin and anti-VEGF agents in neovascular age-related macular degeneration: where do we stand? Br J Ophthalmol 94:143–145

    Article  PubMed  Google Scholar 

  28. Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D (2003) Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 111:1287–1295

    CAS  PubMed  Google Scholar 

  29. Larsen M, Schmidt-Erfurth U, Lanzetta P, Wolf S, Simader C, Tokaji E, Pilz S, Weisberger A, MONT BLANC Study Group (2012) Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month MONT BLANC Study results. Ophthalmology 119:992–1000

    Article  PubMed  Google Scholar 

  30. Spielberg L, Leys A (2010) Treatment of neovascular age-related macular degeneration with a variable ranibizumab dosing regimen and one-time reduced-fluence photodynamic therapy: the TORPEDO trial at 2 years. Graefes Arch Clin Exp Ophthalmol 248:943–956

    Article  CAS  PubMed  Google Scholar 

  31. Vallance JH, Johnson B, Majid MA, Banerjee S, Mandal K, Bailey CC (2010) A randomised prospective double-masked exploratory study comparing combination photodynamic treatment and intravitreal ranibizumab vs intravitreal ranibizumab monotherapy in the treatment of neovascular age-related macular degeneration. Eye (Lond) 24:1561–1567

    Article  CAS  Google Scholar 

  32. Bashshur ZF, Schakal AR, El-Mollayess GM, Arafat S, Jaafar D, Salti HI (2011) Ranibizumab monotherapy versus single session verteporfin photodynamic therapy combined with as needed ranibizumab treatment for the management of neovascular age related macular degeneration. Retina 24:1561–1567

    Google Scholar 

  33. Mataix J, Palacios E, Carmen DM, Garcia-Pous M, Navea A (2010) Combined ranibizumab and photodynamic therapy to treat exudative age-related macular degeneration: an option for improving treatment efficiency. Retina 30:1190–1196

    Article  PubMed  Google Scholar 

  34. Parravano M, Oddone F, Tedeschi M, Chiaravalloti A, Perillo L, Boccassini B, Varano M (2010) Retinal functional changes measured by microperimetry in neovascular age related macular degeneration treated with ranibizumab: 24 months results. Retina 30:1017–1024

    Article  PubMed  Google Scholar 

  35. Jiang L, Jin C, Wen F, Huang S, Wu D, Wu L (2003) The changes of multifocal electroretinography in the early stage of photodynamic therapy for choroidal neovascularization. Doc Ophthalmol 107:165–170

    Article  PubMed  Google Scholar 

  36. Mackay AM, Brown MC, Hagan RP, Fisher AC, Grierson I, Harding SP (2007) Deficits in the electroretinogram in neovascular age-related macular degeneration and changes during photodynamic therapy. Doc Ophthalmol 115:69–76

    Article  PubMed  Google Scholar 

  37. Moschos MM, Panayotidis D, Theodossiadis G, Moschos M (2004) Assessment of macular function by multifocal electroretinogram in age-related macular degeneration before and after photodynamic therapy. J Fr Ophtalmol 27(9 Pt 1):1001–1006

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Fondazione G.B. Bietti-IRCCS, Via Livenza n 3, 00198, Rome, Italy

    Mariacristina Parravano, Vincenzo Parisi, Lucia Ziccardi, Adele Chiaravalloti, Massimiliano Tedeschi, Andrea Cacciamani, Barbara Boccassini, Antonluca Boninfante & Monica Varano

Authors
  1. Mariacristina Parravano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincenzo Parisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucia Ziccardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adele Chiaravalloti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Massimiliano Tedeschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrea Cacciamani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Barbara Boccassini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Antonluca Boninfante
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Monica Varano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mariacristina Parravano.

Additional information

Clinical Trials registration number: EUDRACT number 2007-006235-31.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parravano, M., Parisi, V., Ziccardi, L. et al. Single-session photodynamic therapy combined with intravitreal ranibizumab for neovascular age-related macular degeneration: a comprehensive functional retinal assessment. Doc Ophthalmol 127, 217–225 (2013). https://doi.org/10.1007/s10633-013-9404-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10633-013-9404-z

Keywords

Search

Navigation