Combination therapy with low-dose transpupillary thermotherapy and intravitreal ranibizumab for neovascular age-related macular degeneration: a 24-month prospective randomised clinical study

Br J Ophthalmol. 2012 May;96(5):714-8. doi: 10.1136/bjophthalmol-2011-300721. Epub 2012 Jan 12.


Aim: To compare the effect of combined low-dose transpupillary thermotherapy (TTT) and intravitreal ranibizumab with sham TTT and intravitreal ranibizumab in patients with neovascular age-related macular degeneration (AMD).

Methods: A 24-month, double-masked, randomised, active-controlled clinical trial. 100 patients with primary neovascular AMD were randomly assigned (1:1) to receive intravitreal ranibizumab and sham TTT or intravitreal ranibizumab and low-dose TTT. After an initial loading phase of ranibizumab patients were assigned to receive quarterly low-dose TTT (136 mW/mm) or sham TTT for 24 months. Retreatment with ranibizumab was allowed in both treatment groups using a variable dosing regimen. The primary endpoint was the number of intravitreal injections with ranibizumab. Secondary endpoints included change in best corrected visual acuity (BCVA), central retinal thickness (CRT) and lesion area.

Results: In the per protocol (PP) population (78 patients) the mean number of ranibizumab injections was 8.0 in the sham TTT group versus 6.3 in the TTT group (p<0.05). The mean number of injections between 0-12 months and 13-24 months was 4.8 versus 4.6 (p>0.05) and 3.2 versus 1.7 (p<0.01) in the sham TTT and TTT groups, respectively. There was no statistically significant difference in BCVA (+4.0 vs +0.9 ETDRS letters), CRT (-49.9% vs -36.4%) or lesion area (-0.3% vs -10.6%) between the treatment groups at the final examination. The results of the intent-to-treat population (92 patients) were similar to the PP population.

Conclusions: Treatment with low-dose TTT significantly reduced the number or intravitreal injections of ranibizumab over 24 months. The results suggest that low-dose TTT can serve as an adjuvant in combination with intravitreal ranibizumab for neovascular AMD.

Clinical trial registration number: The trial is registered at (no NCT00599222).

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage*
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Combined Modality Therapy
  • Double-Blind Method
  • Female
  • Fluorescein Angiography
  • Humans
  • Hyperthermia, Induced*
  • Intravitreal Injections
  • Male
  • Prospective Studies
  • Pupil
  • Ranibizumab
  • Retina / pathology
  • Retreatment
  • Time Factors
  • Tomography, Optical Coherence
  • Visual Acuity / physiology
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / physiopathology
  • Wet Macular Degeneration / therapy*


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Ranibizumab

Associated data