First Author: A.Mohite UK
Co Author(s): J. Sardar 0 0 0 0 0 0 0 0 0
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National guidelines stipulate that monthly injections of intravitreal Ranibizumab offer the greatest efficacy in maintaining and improving vision in neovascular AMD. However, financial constraints mean that only the most cost-effective treatments are feasible if a treatment is to be offered to the general population that is free at the point of delivery for every patient that needs it. With this in mind we sought to investigate whether a strict monthly injection protocol, with the additional costs it incurs for NHS hospitals, is really necessary to prevent visual loss from neovascular AMD in comparison to an ‘as needed’ injection protocol.
We therefore investigated the 2-year outcomes of intravitreal Ranibizumab for all types of neovascular AMD in a District General Hospital to compare our outcomes with the major randomised controlled trials quoted in the National Institute for Health and Care Excellence (NICE) guidance.
A retrospective case note review of 99 consecutive treatment-naive eyes (of 86 patients) with neovascular AMD, all of which met the inclusion criteria as defined by NICE guidelines, was undertaken. All cases had a diagnostic fluorescein angiogram (FFA) prior to a loading dose of three injections at monthly intervals. Thereafter, treatment consisted of injections on a pro re nata (PRN) basis guided by optical coherence tomography (OCT) findings and visual acuity at 6-week intervals. This is in contrast to the monthly follow-up suggested by current NICE guidelines and the monthly retreatment used in the ANCHOR and MARINA trials. Rigorous monthly follow-ups were not possible due to various constraints in a busy macular service with limited financial resources. The primary endpoint was a loss of less than 15 letters on the Early Treatment of Diabetic Reinopathy Study (ETDRS) chart at the end of 12 and 24 months. The secondary endpoint was a gain of at least 15 ETDRS letters after 12 and 24 months. Any serious adverse events, including arterial thromboembolic events (ATE’s) were recorded.
The mean age of our cohort was 80.5 years (± 9.6) at presentation, with 64.6% of eyes being female. 60.6% had occult, 29.2% had classic, 5.0% had mixed, and 5.0% had no documentation of CNV subtype. All 99 eyes had 12 month follow-up data but only 77 eyes had 24 month data. Mean baseline vision was 31.7 (± 15.8) ETDRS letters, with mean vision at 12 and 24 months being 30.0 (± 19.0) and 29.2 (± 19.6) letters respectively. The mean time from FFA to first injection was 33.6 (± 18.6) days. The mean number of injections at 12 and 24 months was 4.0 (±1.0) and 5.7 (±2.2) respectively. After 12 months, 86.9% of eyes met the primary endpoint and 11.1% met the secondary endpoint. After 24 months, 80.5% met the primary and 13.0% the secondary endpoints respectively. There were no cases of endophthalmitis. We found a 5.0% (5/99) rate of ATE’s, all of whom had multiple cardiovascular co-morbidities, with two patients dying following these. This is comparable to the MARINA and ANCHOR trials, but since these used more injections per patient, our true ATE rate per injection for each patient is higher than that previously reported.
Our outcomes were comparable, although not quite as good as the major randomised trials which all used monthly injections throughout the whole treatment period. The delay from FFA to first injection in our study may have adversely confounded our results given the natural progression of the condition. Gain in visual acuity at 24 months was much higher (33-40%) in the major trials than the 13% we achieved. Therefore, our results demonstrate that a PRN regime using fewer injections can be similarly effective as monthly injections in stabilising visual acuity, but less effective in gaining acuity after 24 months. ‘As needed’ injection regimes may be a cost-effective means of achieving similar results in a health system with limited resources such as the National Health Service. Ranibizumab may be associated with a higher incidence of ATE’s in those with known vascular co-morbidities than previously thought. This potentially makes a PRN regime that utilises both a lower dosing frequency and total number of injections safer for ‘at risk’ patients, albeit at a slight compromise with regard to the long term visual gain at 24 months.