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Combination therapy with low-dose transpupillary thermotherapy and intravitreal ranibizumab for neovascular age-related macular degeneration: a 24-month prospective randomised clinical study
  1. Anne-Catherine Söderberg1,
  2. Peep V Algvere1,
  3. Jürg C Hengstler1,
  4. Pär Söderberg2,
  5. Stefan Seregard1,
  6. Anders Kvanta1
  1. 1Department of Ophthalmology, Karolinska Institutet, St Eriks Eye Hospital, Stockholm, Sweden
  2. 2Ophthalmology, Department of Neuroscience, Uppsala University, Uppsala, Sweden
  1. Correspondence to Dr Anders Kvanta, Department of Ophthalmology, St Eriks Eye Hospital, Polhemsgatan 50, SE-11282 Stockholm, Sweden; anders.kvanta{at}


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).

  • Angiogenesis
  • experimental and laboratory
  • neovascularisation
  • pathology
  • treatment medical
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  • Competing interests None.

  • Ethics approval This investigation was approved by the Regional Ethical Review Board in Stockholm and by the Swedish Medical Products Agency (EU-nr 2007-005462-12).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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