Treatment Of Radiation Retinopathy Trial (TORR)

• To evaluate the time course of BCVA changes on ranibizumab (0.5 mg) and triamcinolone acetonide (4.0mg) relative to no treatment. [ Time Frame: one year ] [ Designated as safety issue: No ]
• To evaluate the effects of ranibizumab (0.5 mg) and triamcinolone acetonide (4.0mg) on central retinal thickness, severity of retinopathy and other anatomical changes relative to no treatment [ Time Frame: one year ] [ Designated as safety issue: No ]
• To demonstrate a possible relation between decreasing levels of angiogenic factors (such as VEGF) in the anterior chamber fluid and a good response to treatment with ranibizumab or triamcinolone acetonide, and radiation retinopathy [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

The purpose of this study is to demonstrate a statistically significant improvement of visual acuity after treatment using either Lucentis® or Triamcinolone® compared to no treatment, in patients with radiation retinopathy.

Approximately 30-40% of patients develop a deterioration of visual acuity within 5 years after treatment of uveal melanoma using radiation therapy and TTT due to radiation retinopathy (Shields 2002, Bartlema 2003). By administration of either Lucentis® or Triamcinolone® we hope to treat complications of radiation therapy, by demonstrating a statistically significant improvement in visual acuity and a reduced amount of macular edema and vascular leakage. Additionally, we hope to obtain a better understanding of the pathophysiologic processes involved, by demonstrating a possible relation between high levels of angiogenic factors (VEGF) in the anterior chamber fluid, and radiation retinopathy. In conclusion, we hope to provide evidence for a new therapy in patients with retinopathy, due to radiation in uveal melanoma. There is no scientifically proven treatment available at this time.

• Drug: ranibizumab
  three initial monthly intra vitreal injections with 0.5 mg ranibizumab
• Drug: triamcinolone acetonide
  at baseline one intra vitreal injection with 4.0 mg triamcinolone acetonide
• Other: sham
  at baseline one sham-injection

• Active Comparator: 1: Lucentis
  Intervention: Drug: ranibizumab
• Active Comparator: 2: Kenalog
  Intervention: Drug: triamcinolone acetonide
• Sham Comparator: 3: No treatment
  Intervention: Other: sham

Inclusion Criteria:

• The eye was previously irradiated for treatment of a uveal melanoma;
• Decrease of visual acuity after irradiation therapy by more than 10 letters (ETDRS) and is now 20/40 or less;
• Vision decrease is considered to be due to central radiation retinopathy with significant macular edema or optic disc edema;
• Age 18 years or older;
• The patient is fully competent;
• Written informed consent to participate in the trial is given.
• Patient is not pregnant (or not fertile) and is willing to use contraceptives for the duration of the trial (one year)
• Patient is willing and able to return for follow-up.

Exclusion Criteria:

• Vision decrease is considered to be due to ischemic radiation retinopathy without macular edema or optic disc edema;
• Other, approved therapy indicated for treatment of condition;
• Presence of metastasis;
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial;
• Pre-existing retinopathy due to other disorders;