The LIMO Study, Lucentis for Treatment of Uveitic Patients With Refractory Cystoid Macular Oedema

• The number of patients in whom, by consensus, no further treatment is required. [ Time Frame: Data will be collected at every patient visit which will take place every 4-5 weeks, and analysed at 12 months follow-up ] [ Designated as safety issue: No ]
  Intravitreal Ranibizumab will be given at baseline, month 1 and month 2 . Subsequent 4-5 weekly injections will be given according to clinical need. There will be a total of 12 months of follow-up.
  
  
• Change in CRT as measured by Spectralis spectral domain OCT. [ Time Frame: at baseline visit then at 6 and 12 months. ] [ Designated as safety issue: Yes ]
  

• Functional vision changes based on self-reported quality of life measures (including acceptability of 4 weekly intravitreal therapy). [ Time Frame: at baseline visit then at 6 and 12 months. ] [ Designated as safety issue: Yes ]
  
• The proportion of subjects gaining >10 and >15 letters. [ Time Frame: at baseline vist, on day 7 and day 14, then on monthly basis. ] [ Designated as safety issue: Yes ]
  
• Change in contrast sensitivity. [ Time Frame: at baseline visit then at months 1, 3, 6, 9 and 12. ] [ Designated as safety issue: Yes ]
  
• Change in BCVA. [ Time Frame: at baseline visit then at 3, 6, 9 and 12 months. ] [ Designated as safety issue: Yes ]
  
• The proportion of subjects with loss of >15 letters and >30 letters. [ Time Frame: at baseline vist, on day 7 and day 14, then on monthly basis. ] [ Designated as safety issue: Yes ]
  
• Change in retinal sensitivity on microperimetry. [ Time Frame: at baseline visit then on month 3, 6, 9 and 12. ] [ Designated as safety issue: Yes ]
  
• Change in reading speed. [ Time Frame: at baseline visit, months 1, 3,6, 9 and 12. ] [ Designated as safety issue: Yes ]
  
• Evidence of improvement in PERG or mfERG. [ Time Frame: at baseline visit, month 4, and 12. ] [ Designated as safety issue: Yes ]
  
• Maintenance of the foveal avascular zone. [ Time Frame: at baseline, 6 and 12. ] [ Designated as safety issue: Yes ]
  
• Absence of toxicity on Electrophysiological testing / microperimetry / autofluorescence. [ Time Frame: at baseline visit then on month 3, 4,6, 9 and 12. ] [ Designated as safety issue: Yes ]
  
• Incidence and severity of ocular adverse events. [ Time Frame: at day 7, day 14, month 1 then every month until 12 month post initial intravitreal injection ] [ Designated as safety issue: Yes ]
  
• Incidence and severity of non ocular adverse events. [ Time Frame: at day 7, day 14, month 1 then every month until 12 month post initial intravitreal injection ] [ Designated as safety issue: Yes ]
  

The study has been designed as an open label, prospective non-randomised interventional case series.

Clinical staff will be asked to briefly discuss the option of enrolling into the study with potentially suitable patients. If the patient expresses an interest in finding out more about the study, the doctor will then contact a member of the study team, who will provide the patient with the patient information leaflet. This outlines the details and purpose of the study, the intended benefits of the intravitreal treatment and the potential hazards (including the unlicensed use of Ranibizumab for this indication). The intravitreal injection procedure will be discussed. The follow-up schedule will be outlined. There will be an opportunity for the patient to ask questions and at least 24 hours for the patient to think about entering the study. Only 1 eye of each patient, the worse eye, will be enrolled.

Comprehensive pre- and post- therapy and a longitudinal series of structure and function tests will be performed on all 20 enrolled patients. All patients will receive intravitreal injections performed in a designated clean room. The injections (Ranibizumab 0.5 mg in 0.05 ml) will be administered 4-5 weekly, for three injections then according to clinical need for a total of 12 months of follow-up. A maximum of 5 intravitreal Ranibizumab injections will be administered to patients who do not demonstrate any positive clinical response.

The patients will be seen for baseline screening over a 2 day period, with the first treatment with Ranibizumab administered on the second day (maximum of 10 working days after the first baseline screening day). Subsequent to the first 3 injections, the investigator will assess whether re-treatment is warranted (clinical / OCT criteria set out in re-treatment protocol). Re-treatment, when indicated, will be performed on the same day as the follow-up visit and no sooner than 4 weeks or later than 5 weeks from the time of the last treatment. If re-treatment with IVI Ranibizumab is to be deferred patients will not be given a sham injection. Should a relapse in ocular inflammation occur, it might be difficult to differentiate as to whether this is because of the drug or the underlying disease. A mild flare up, Lucentis-related or not, may be observed and treated with topical therapy (but patient will remain in the study). A moderate to severe recurrence, regardless of the cause which will necessitate more extensive therapy, namely a change or addition of systemic therapy, will result in the patient exiting the study-this would be an end point.