1. TA298 Ranibizumab for treating choroidal neovascularisation associated with pathological myopia Dr.Muhammad Hamza North Devon District NHS Hospital NICE GUIDLINE

2. CNV is a common cause of vision loss in people with pathological myopia. There are approximately 200,000 people with pathological myopia in the UK. The prevalence or incidence of CNV associated with pathological myopia in the UK is not known. However, approximately 30% of people who develop CNV in one eye will develop it in the other eye within 8 years

3. Indication Patients of any age undergoing treatment for choroidal neovascularisation (CNV) secondary to pathological myopia (PM), including patients with concomitant ocular disease

4. Dosage Ranibizumab is administered as a single 0.5 mg intravitreal injection. Each vial of ranibizumab contains 2.3 mg in 0.23 ml; overfilling is considered necessary to achieve an injectable dose of 0.5 mg. The summary of product characteristics states that monitoring is recommended monthly for the first 2 months and at least every 3 months thereafter during the first year. If monitoring reveals signs of disease activity, for example, reduced visual acuity and/or signs of lesion activity, further treatment is recommended Major Outcomes Considered Clinical effectiveness Best corrected visual acuity in the studied eye Adverse effects of treatment Health related quality of life Cost-effectiveness

5. The approval was supported by data from the Novartis- sponsored clinical trial, RADIANCE, which showed ranibizumab provides superior improvement in visual acuity compared with the current licensed standard of care, verteporfin PDT (Visudyne®), in patients with CNV secondary to PM. These new data showed around 40 percent of ranibizumab treated patients compared with 15 percent of verteporfin PDT treated patients gained 15 or more letters of visual acuity at month three ( 4). Mean visual acuity gains of approximately 14 letters at one year were demonstrated with ranibizumab; this was with a median of 2.0 injections (1,2).

6. Contraindications Contraindications to ranibizumab include known hypersensitivity to the active substance or to any of its excipients, active or suspected ocular or periocular infections, and active severe intraocular inflammation.

7. Current practice The Committee heard that the current standard treatment for choroidal neovascularisation secondary to pathological myopia is vPDT. However, it is not effective in most patients and its use is diminishing because of anti ‑ VEGF treatments.

8. Risk of Complication Vitreous floaters, Conjunctival haemorrhage Sensation of a foreign body in the eye Eye pain, Ocular hyperaemia, Increased intraocular pressure, Vitritis, Vtreous detachment. The Committee agreed that the evidence suggested manageable adverse events with ranibizumab, and concluded that ranibizumab was safe and well tolerated in patients with visual impairment caused by choroidal neovascularisation associated with pathological myopia.

9. Followup Pivotal trial shows average visual acuity improvement of up to 14 letters at one year with a median of only two injections with Lucentis treatment

10. Implementation When NICE recommends a treatment 'as an option', the NHS must make sure it is available for the patients.

11. The key drivers of cost effectiveness The manufacturer's sensitivity analyses showed that the cost effectiveness of ranibizumab was sensitive to changes in the unit cost of ranibizumab and vPDT, the number of ranibizumab injections in the first and second year, the starting age of the patient group, the discount rate for benefits, and the maximum utility gain in the worse ‑ seeing eye.

12. Future The Committee noted that the primary end point of RADIANCE was the mean average change in BCVA between baseline and months 1–3. The Committee heard from a clinical specialist that 3 months was not a long timeperiod to assess the longer term benefits of ranibizumab.The Committee concluded that, because the clinical effectiveness of ranibizumab was not compared with vPDT after 3 months, there is uncertainty about the long-term efficacy of ranibizumab for choroidal neovascularisation associated with pathological myopia. Review of guidance 7.1 The guidance on this technology will be considered for review in March 2016.

13. References 1 Bandello F. Twelve-month efficacy and safety of ranibizumab 0.5 mg versus verteporfin photodynamic therapy in the treatment of visual impairment due to choroidal neovascularization secondary to pathologic myopia. Association for Research in Vision and Ophthalmology 2013 2 Novartis data on file: LUCDOF13-009 3 NICE, 2012, available online: http://www.nice.org.uk/nicemedia/live/14019/63645/63 645. http://www.nice.org.uk/nicemedia/live/14019/63645/63 645 4 Novartis data on file: LUCDOF 13-010 pdf accessed July 2013