The National Institute for Health and Care Excellence (NICE) has issued final guidance recommending ranibizumab (Lucentis, Novartis) as a treatment for sight problems caused by macular oedema, a condition which affects a person's ability to see detail and colour. The new guidance relates to macular oedema caused by retinal vein occlusion (RVO) where the vein to the retina or one of its branches is blocked (central or branch retinal vein occlusion). NICE recommends the treatment should only be prescribed if the manufacturer makes it available to the NHS under terms agreed with the Department of Health as part of a patient access scheme.

The macula is the central part of the retina responsible for seeing colour and fine detail. Macular oedema occurs when fluid collects in the retina at the macular area, which can lead to severe visual impairment in the affected eye. Straight lines may appear wavy, and people can have blurred central vision or sensitivity to light. A reduction in the number of connective tissues around the capillaries and an increased amount of a protein called vascular endothelial growth factor (VEGF) causes the blood retinal barrier to become porous. This leads to plasma in the surrounding retina, causing a build-up of excess fluid (oedema) which disrupts the fovea, the area of the eye responsible for sharp vision.

The guidance recommends ranibizumab as an option for treating macular oedema following central retinal vein occlusion (CRVO)ⁱ. It also recommends the drug as a treatment option following branch retinal vein occlusion (BRVO)ⁱⁱ only if standard treatment with laser photocoagulation (where a laser is used to seal ocular blood vessels) has not worked, or when it is not suitable because of the extent of macular haemorrhage.

Professor Carole Longson, Director of the Health Technology Evaluation Centre at NICE said: “Macular oedema can cause blurred vision or a sensitivity to light, both of which can be very frightening and can significantly affect a person's everyday life. These symptoms can come on suddenly, and if left untreated can cause blindness.

“NICE is, therefore, pleased to recommend ranibizumab in people with CRVO and some people with BRVO, following the submission of a patient access scheme, which makes the treatment more cost effective.”

The incidence of RVO increases with age. Other risk factors for RVO include high blood pressure, hyperlipidaemiaⁱⁱⁱ, glaucoma^iv, thrombophilia^v and diabetes.

Ranibizumab, which is given by injection into the eye, works by preventing the production of VEGF. By inhibiting VEGF, ranibizumab can decrease the oedema and limit visual loss and/or improve vision.

Ends

The guidance can be found from 00:01hrs on Wednesday 22 May 2013

Notes to Editors

References and explanation of terms

i. CRVO results from thrombosis of the central retinal vein where it passes through the back of the optic nerve through a mesh-like structure called the lamina cribrosa.

ii. BRVO is caused by venous thrombosis at an arteriovenous crossing (where an artery and vein share a common lining of connective tissue).

iii. Hyperlipidaemia occurs when there is an excessively high level of lipids / fats in the blood.

iv. Glaucoma is the name given to a group of eye conditions which cause optic nerve damage that affects vision.

v. Thrombophilia is a condition in which the blood has an increased tendency to form clots.

About the guidance

1. The guidance can be found from 00:01hrs on Wednesday 22 May 2013on the NICE website

Embargoed copies are available on request; please contact the press office.

2. RVO is a common cause of reduced vision due to retinal vascular disease. It is classified into BRVO and CRVO. Thrombosis of the retinal veins causes an increase in retinal capillary pressure, resulting in the capillaries being more permeable, and the discharge of blood and plasma into the retina. This leads to the development of macular oedema and varying levels of ischaemia (a restriction in blood supply) through non-perfusion of capillaries. These changes trigger an increased amount of vascular endothelial growth factor (VEGF), which increases vascular permeability and new vessels developing.

3. The current standard treatment for macular oedema secondary to BRVO is grid laser photocoagulation. However, grid laser photocoagulation is not an option for people with CRVO and the current standard treatment is dexamethasone or anti-VEGF drugs such as bevacizumab.

4. Ranibizumab (Lucentis, Novartis) belongs to a class of drugs that block the action of vascular endothelial growth factor A (VEGF-A).

5. Ranibizumab has a marketing authorisation for ‘the treatment of visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO)'. For more details see the summary of product characteristics (SPC).

6. Ranibizumab is administered as a single intravitreal injection of 0.5 mg. Each vial of ranibizumab contains 2.3 mg in 0.23 ml. Ranibizumab costs £742.17 per vial (excluding VAT; 'British national formulary' [BNF] edition 64).

7. The guidance follows consideration of further evidence and a patient access scheme submitted by the manufacturer, as well as the results of further work carried out by the NICE Decision Support Unit.

8. The independent Appraisal Committee concluded that ranibizumab is a clinically and cost-effective treatment option for non-ischaemic macular oedema secondary to CRVO and secondary to BRVO only if treatment with laser photocoagulation has not been beneficial, or when laser photocoagulation is not suitable because of the extent of macular haemorrhage.

9. The Department of Health and the manufacturer have agreed that ranibizumab will be available to the NHS with a patient access scheme,revised in the context of NICE technology appraisal guidance 274, which makes ranibizumab more cost effective. The terms of the agreement are commercial in confidence.

10. Ranibizumab was associated with an ICER of £26,200 per QALY gained compared with best supportive care in CRVO.

11. The Committee concluded that the most plausible ICER for ranibizumab compared with standard care in treating the full patient population of BRVO was in excess of £44,800 per QALY gained. This ICER (£44,800) is above the usual range considered cost-effective (£20,000-£30,000 per QALY gained). For the smaller population of people with BRVO who can receive dexamethasone (when laser treatment is inappropriate as recommended in NICE technology appraisal guidance 229), the ICER's ranged from the manufacturer's pairwise ICER of £2400 per QALY gained (including the patient access scheme as revised in the context of NICE technology appraisal 274) to the ERG's exploratory ICER of £4100 per QALY gained (including correction of the maximum utility benefit in the ‘worse-seeing eye'). The Committee concluded that although there was uncertainty around this estimate of £4100 per QALY gained because of both the confounding in the BRAVO trial, and the uncertainty in the dexamethasone indirect comparison, ranibizumab could be considered an option in people with BRVO for whom grid laser photocoagulation has not been beneficial or is not suitable because of the extent of macular haemorrhage.

12. People currently receiving ranibizumab whose disease does not meet the criteria in the guidance should be able to continue treatment until they and their clinician consider it appropriate to stop

13. The NICE Decision Support Unit (DSU) is commissioned by the Institute to provide a research and training resource to support the Institute's Technology Appraisal Programme. Further information on the NICE Decision Support Unit can be found at: http://www.nicedsu.org.uk/

14. The timelines for NICE's appraisal of ranibizumab were extended to enable the results of further work related to the use of bevacizumab (Moorfields Eye Hospital Pharmaceuticals and Royal Liverpool and Broadgreen University Hospital Pharmacy) as a comparator in this appraisal to become available. NICE commissioned this additional work following consultation on the previous draft recommendations which did not recommend ranibizumab. The appraisal was also extended to allow the patient access scheme (revised in the context of NICE technology appraisal guidance 274) to be considered.

15. NICE technology appraisals apply across the NHS in England and Wales.

16. NICE technology appraisals are normally enforceable three months from the date of publication.

17. For further details on NICE technology appraisals, please see the NICE website

Related guidance

Published

18. In February 2013, NICE recommended ranibizumab for treating diabetic macular oedema (rapid review of technology appraisal 237). NICE technology appraisal guidance 274.

19. In January 2013, NICE did not recommend fluocinolone acetonide intravitreal implant for the treatment of chronic diabetic macular oedema after an inadequate response to prior therapy. NICE technology appraisal guidance 271.

20. In July 2011, NICE recommended dexamethasone (Ozurdex, Allergan) for the treatment of macular oedema secondary to retinal vein occlusion (RVO). NICE technology appraisal guidance 229.

21. In August 2008, NICE published guidance recommending ranibizumab for the treatment of age-related macular degeneration. It did not recommend pegaptanib for the same indication. NICE technology appraisal guidance 155. In May 2012, this guidance was re-issued after a change to the patient access scheme.

In development

22. Aflibercept solution for injection for the treatment of macular oedema caused by central retinal vein occlusion. Publication date is expected in April 2014.

23. The Scottish Medicines Consortium (SMC) has recommended ranibizumab for for restricted use within NHS Scotland. It is restricted to use in patients with macular oedema secondary to central retinal vein occlusion (CRVO).

24. The SMC has recommend ranibizumab for the treatment of diabetic macular oedema for restricted use within NHS Scotland, contingent upon the continuing availability of a patient access scheme that improves the cost-effectiveness of ranibizumab.

About NICE

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