Macular EpiRetinal Brachytherapy Versus Lucentis® Only Treatment (MERLOT)
Condition: Macular Degeneration
MeSH terms: Macular Degeneration
Intervention: Epimacular Brachytherapy; Ranibizumab
Intervention description: Strontium-90. The device delivers 24 Gray of beta radiation to the choroidal neovascular membrane (CNV) lesion. Each device is calibrated for a set duration.; intravitreal injection of Ranibizumab (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Intervention MeSH terms: Ranibizumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 363.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Wet Age-related Macular Degeneration; Predominantly classic; Minimally classic; Occult with no classic; Retinal Angiomatous Proliferation (RAP) lesions

Summary:

      Wet age-related macular degeneration is the most common cause of blind registration in the
      United Kingdom (UK). Standard treatment involves regular eye injections of a drug called
      ranibizumab (Lucentis). For most patients, ranibizumab maintains their vision but the effect
      of the drug is temporary, and they therefore require monthly hospital visits and typically
      six injections into the eye every year, probably for life.

      This study tests a new surgical device that delivers a focal dose of radiation (epimacular
      brachytherapy) to the macula (the part inside the back of the eye that gives fine central
      vision), to try and reduce or eliminate the need for ongoing, regular eye injections. The
      trial compares epimacular brachytherapy to ongoing standard treatment with ranibizumab.

      Whereas most studies of this new surgical device target patients who have not yet commenced
      any treatment, this study targets those who are requiring frequent eye injections, as there
      are limited surgical resources and these resources are best directed to those who have not
      fully responded to ranibizumab therapy, or whose response is shortlived. These patients have
      the most to gain from a device that may reduce their burden of treatment. The findings in
      untreated disease cannot be extrapolated to this discrete subset of patients, hence the need
      for a study that targets refractory disease.

      It is hypothesised that epimacular brachytherapy will reduce the frequency of Lucentis®
      (ranibizumab) re-treatment that patients require, whilst maintaining visual acuity.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects with subfoveal choroidal neovascularisation associated with wet age-related
             macular degeneration. Retinal Angiomatous Proliferation (RAP) lesions not directly
             involving the fovea must be associated with contiguous foveal leakage demonstrated on
             fundus examination, optical coherence tomography (OCT), or fluorescein angiography;

          2. Subjects must have received anti-VEGF induction treatment, defined as the first three
             months of anti-VEGF therapy. Following this induction period, subjects must have
             received at least 4 additional injections of Lucentis® in no more than 12 months
             preceding enrolment, or 2 additional injections of Lucentis® in no more than 6 months
             preceding enrolment, given on an as needed basis;

          3. At the time subjects commenced anti-VEGF therapy for wet age-related macular
             degeneration they were aged 50 years or older and met the NICE treatment criteria for
             Lucentis® therapy, as outlined in the Final Appraisal Determination (FAD). This states
             that all of the following circumstances must apply in the eye to be treated:

               -  the best-corrected visual acuity is between 6/12 and 6/96 (24 to 69 ETDRS
                  letters)

               -  there is no permanent structural damage to the central fovea

               -  the lesion size is less than or equal to 12 disc areas in greatest linear
                  dimension

               -  there is evidence of recent presumed disease progression (blood vessel growth, as
                  indicated by fluorescein angiography, or recent visual acuity changes)

        Exclusion Criteria:

          1. Patients who have not been treated in accordance with NICE guidance;

          2. Visual acuity worse than 6/96 at the time of study enrolment;

          3. Subjects with prior or concurrent subfoveal CNV therapy with agents, surgery or
             devices (other than Macugen®, Avastin®, or Lucentis®) including thermal laser
             photocoagulation (with or without photographic evidence), photodynamic therapy,
             intravitreal or subretinal steroids, and transpupillary thermotherapy (TTT);

          4. Subfoveal scarring;

          5. Subjects with active concomitant disease in the study eye, including uveitis, presence
             of pigment epithelial tears or rips, acute ocular or periocular infection;

          6. Subjects who have been previously diagnosed with Type 1 or Type 2 Diabetes Mellitus.
             Subjects who do not have a documented diagnosis, but have retinal findings consistent
             with Type 1 or Type 2 Diabetes Mellitus;

          7. Subjects with advanced glaucoma (greater than 0.8 cup:disk) or intraocular pressure ≥
             30 mmHg in the study eye;

          8. Previous glaucoma filtering surgery in the study eye;

          9. Subjects with inadequate pupillary dilation or significant media opacities in the
             study eye, including cataract, which may interfere with visual acuity or the
             evaluation of the posterior segment;

         10. Current vitreous haemorrhage in the study eye;

         11. History of rhegmatogenous retinal detachment or macular hole in the study eye;

         12. Subjects who present with CNV due to causes other than AMD, including subjects with
             known or suspected idiopathic polypoidal choroidal vasculopathy (IPCV), ocular
             histoplasmosis syndrome, angioid streaks, multifocal choroiditis, choroidal rupture,
             or pathologic myopia (spherical equivalent ≥ 8 Dioptre or axial length ≥ 25mm);

         13. Subjects who have undergone any intraocular surgery in the study eye within 12 weeks
             prior to the screening visit, with the exception of cataract surgery as discussed in
             the Exclusion Criteria #14

         14. Previous cataract surgery within 2 months prior to enrolment into the study;

         15. Subjects with known serious allergies to fluorescein dye used in angiography;

         16. Subjects with known sensitivity or allergy to Lucentis®;

         17. Subjects who underwent previous radiation therapy to the eye, head or neck;

         18. Subjects with an intravitreal device or drug in the study eye;

         19. Subjects with any other condition, which in the judgment of the investigator would
             prevent the subject from completing the study (e.g. documented diagnosis of dementia
             or serious mental illness);

         20. Current participation in another drug or device clinical trial, or participation in
             such a clinical trial within the last year;

         21. History of use of drugs with known retinal toxicity, including: chloroquine (Aralen -
             an anti-malarial drug), hydroxychloroquine (Plaquenil), phenothiazines, chlorpromazine
             (Thorazine), thioridazine (Mellaril), fluphenazine (Prolixin), perphenazine
             (Trilafon), and trifluoperazine (Stelazine);

         22. Subjects who are unwilling or unable to return for scheduled treatment and follow-up
             examinations for three years;

         23. Women must be post-menopausal more than 1 year unless surgically sterilised