Real-world strategies for wet AMD

February 29, 2016

In many clinical areas, early consultant-led intervention has been shown to improve clinical and patient-reported outcomes and to reduce overall treatment costs. This paper reconfirms this finding in the treatment of wet age-related macular degeneration (wet AMD) and presents data from a publicly funded NHS fast-track (FT) centre in north-west England that aims to see and treat patients within 48 hours of referral.

Reviewed by Winfried Amoaku, associate professor/reader and honorary consultant ophthalmologist at the University of Nottingham, and Nottingham University Hospitals Trust 

In many clinical areas, early consultant-led intervention has been shown to improve clinical and patient-reported outcomes and to reduce overall treatment costs.

This paper reconfirms this finding in the treatment of wet age-related macular degeneration (wet AMD) and presents data from a publicly funded NHS fast-track (FT) centre in north-west England that aims to see and treat patients within 48 hours of referral.

Outcomes, in this real-world setting and at commissioning scale, exceed those from clinical studies.

National treatment guidelines are not onerous but are nevertheless often not met, and this paper reinforces the clinical benefits of early and on-protocol treatment and the consequent importance of patient, provider and commissioner education.

Given the cost to patients and society of poor compliance and outcomes, we call for systematic monitoring of performance metrics on a national scale.


Wet AMD is a common eye condition that leads to rapid and progressive loss of central vision and severe visual impairment.

Two agents, the anti-vascular endothelial growth factor (VEGF) antibody ranibizumab (Lucentis, Novartis) and the VEGF trap aflibercept (Eyelea, Bayer), have been shown to be highly effective in inhibiting the neovascularisation that is characteristic of wet AMD and stabilising or improving vision in most patients.

Two pivotal randomised controlled trials, ANCHOR1 and MARINA,2 underpin the use of intravitreal ranibizumab in the treatment of wet AMD. In the ANCHOR study, in which ranibizumab was administered on a four-weekly basis over two years, visual acuity (VA) improved by 15 or more letters in 40.3% of patients, with a mean improvement of 11.3 letters at one year and 10.7 letters at two years.

Background (cont.)


The MARINA study showed that, at 12 months, 94.6% of patients had lost fewer than 15 letters of vision, VA had improved by 15 or more letters in 33.8% of patients and the overall mean improvement was 7.2 letters. The PrONTO study3 subsequently demonstrated the equivalent effectiveness of pro re nata (PRN) administration after initial stabilisation of the lesion, using optical coherence tomography (OCT) parameters to dictate treatment.

Mean VA increased by 9.5 letters at 12 months and 10.7 letters at 24 months. Baseline vision was maintained by 78% of patients and VA improved by 15 letters or more in 43% of patients. Subsequent ranibizumab studies have further improved these treatment models, including the validation of treat and extend, which achieves similar outcomes.4

The overall effectiveness of all of these pathways depends on both the time from symptom onset to treatment initiation and compliance with subsequent treatment protocols. Although the Royal College of Ophthalmologists recommends treatment within two weeks of initial referral,5 many, if not most, providers routinely fail to achieve these targets and real-world results fall considerably short of those expected from clinical trials.6–8.

This is generally attributed to capacity constraints reducing treatment frequency, case-mix, loss of patients to follow-up and difficulty with transportation.9

On the other hand, it is widely acknowledged that early and protocol-compliant consultant-led intervention improves outcomes and reduces overall healthcare journey costs in a range of disease areas.10

This paper re-examines this principle in the treatment of wet AMD, and reports one-year data from a newly established fast-track service that aims to see and treat patients within 48 hours of referral, in strict accordance with existing PRN protocols.

Fast-track treatment of wet AMD


Fast-track treatment of wet AMD

We set out to build a wet AMD service able to confirm a diagnosis of wet AMD and initiate VEGF inhibition within 48 hours of referral. This timeline was selected as being ambitious yet deliverable within the constraints of the normal Monday-to-Friday working of a secondary care ophthalmology unit.

By building a responsive and flexible capacity, able to urgently accommodate the patient on the day of referral or the following day and to initiate treatment at the same visit, only patients mis-directed through non-FT gateways, those unwilling or unable to present urgently or those referred at close of day on a Friday would necessarily fall outside of the 48-hour window.

Following a consultant-delivered optometrist education programme, a direct fax-based FT pathway was established across a clinical commissioning group (CCG) area for the urgent referral of all cases of suspected AMD. Upon referral, patients are immediately telephoned by an AMD specialist nurse, advised of the importance of early disease intervention and offered an appointment that day or the next.

Beginning the process of informed consent and expectation management, patients are advised that treatment may be required at the first visit and given a 24/7 contact number for the service.

Upon attendance, the patient is treated exclusively by the same specialist AMD nurse, who conducts diagnostic tests including LogMAR vision and OCT (Spectralis, Heidelberg) and arranges fluorescein angiography for a second visit.

Results are discussed with a sub-specialist retinal consultant and a definitive diagnosis made at the first presentation using well-established and widely used clinical protocols.

Following a diagnosis of wet AMD and establishment of eligibility under NICE guidelines, patients are listed directly for intravitreal injection, accommodated within existing cataract procedure scheduling or included in a dedicated injection list.

Injections are conducted in a sterile operating environment, using established methods and protocols, by ophthalmic consultant surgeons and a specialist AMD nurse.

Following the first appointment, the referring optometrist is telephoned by the AMD nurse and informed of the patient’s clinic attendance and diagnosis. Injections and follow-up investigations are conducted according to existing PRN pathways as shown in Box 1.


Box 1. PRN protocol for the management of wet AMD


One-year results


One-year results

Overall, 165 patients from a single CCG were referred to the newly established macular service during the 15-month period from September 2014, with 73 (44.2%) referred through the accelerated (FT) channel, and the remainder through routine non-FT pathways.

The wet AMD diagnosis was confirmed in 62 (84.9%) FT and 22 (23.9%) non-FT patients who were treatment naive and met the criteria for treatment with Lucentis. Fourteen patients had bilateral disease; therefore, 98 eyes in total were treated.

One patient was excluded from the study on leaving the country and two patients suffered unrelated excluding events.

Figure 1 shows referral to treatment time performance for FT and non-FT groups. In the FT group, 56.8% of patients were seen and treated within 48 hours of referral, with 94.8% seen and treated within one week.

The equivalent figures for non-FT patients are 21.4% and 52.4%, respectively. The subsequent treatment of 84% of patients (both FT and non-FT) was fully compliant with the Box 1 protocol for all appointments and injections, with remaining patients deviating by less than two weeks, largely as a result of patient availability.

Figure 2 shows the resulting mean improvement in VA over the 12-month period: 7.2 letters for all wet AMD patients and 8.8 letters for FT patients. In 95.3% of patients, VA deteriorated by less than 15 letters; 30.2% of patients had an improvement of more than 15 letters. Baseline vision was maintained or improved in 81.4% of patients.

(FIGURE 1) Cumulative referral to injection time performance for fast-track and non-fast-track patients. Colours indicate compliance with existing RCOphth guidelines.(5)

(FIGURE 2) Mean VA change in fast-track and all-patient treatment groups.















Despite a failure to meet the target to see and treat every single patient within 48 hours of referral, results from the service are highly consistent with those of the ANCHOR and MARINA studies and suggest that the level of performance achieved in clinical trials is achievable in real-world practice through earlier intervention and improved protocol adherence.

The relative contribution of these elements merits further investigation.

Implementation of treatment within 48 hours is not, however, without challenge. Notably, despite consultant-delivered education and one-to-one feedback, patients continued to be referred through non-urgent channels.

Achievement of see-and-treat targets were also limited by patient lack of readiness to undergo intravitreal injection as an urgent procedure, despite attempts to manage patient expectations from the first contact.

Inevitably, some patients were also unable to be accommodated urgently within existing activities and there was a continual need to reinforce clinical urgency in scheduling practices more normally used to elective activity.

Nevertheless, existing routine activity need not be dramatically disturbed by the integration of urgent pathways; although secondary care ophthalmology is usually treated as a scheduled care specialty with limited requirement for acute unplanned activity, the service described here was developed with limited impact on the existing pathways with which it shares equipment, operating facilities and staff.

This was achieved through the real-time adjustment of capacity and resource allocation based on demand, supported by a detailed administrative and booking framework. An integrated team commitment to the delivery of gold-standard care across all pathways was further motivated by significant patient success stories.

This ability of the service to provide treatment at short notice improved throughout the period of study as a result of increased experience and the existence of dedicated injection lists primarily occupied by follow-up patients.

This would indicate that existing providers could perhaps adapt readily to firmer treatment scheduling.

Concluding comments


Concluding comments

This paper describes our experience of establishing a 48-hour wet-AMD treatment service and demonstrates that reference-standard outcomes are achievable in the real-world setting, at typical (250,000 population) commissioning scale and at no additional cost over existing pathways.

Nationally, wet AMD services are highly variable and it is likely that the vision of several thousand UK patients per year, along with the estimated costs associated with blindness, could be saved through faster, protocol-compliant wet AMD pathways.

This paper highlights the importance of educating providers, commissioners and healthcare regulators to expect, monitor and enforce higher standards in the treatment of wet AMD and, given the considerable personal and societal costs of sight loss, we propose urgent implementation of centralised systematic performance monitoring on a national scale.



1.     D.M. Brown et al., Ophthalmology 2009; 116(1): 57-65.e5.

2.     P.J. Rosenfield et al.,N. Engl. J. Med. 2006; 355(14): 1419-1431.

3.     G.A. Lalwani et al., Am. J. Ophthalmol. 2009; 148(1): 43-58.e1.

4.     J.J. Arnold et al., Ophthalmology 2015; 122(6): 1212-1219.

5.     Royal College of Ophthalmology. Guidelines on the management of macular disease. September 2013, p106.

6.     Writing Committee for the UK Age-Related Macular Degeneration EMR Users Group. Ophthalmology 2014; 121(5): 1092-1101.

7.     R. Chevan et al.,Clin. Ophthalmol. 2014; 8: 717-723.

8.     F.G. Holz et al., Br. J. Ophthalmol. 2014. Published online first on Sept. 5th 2014. doi:10.1136/bjophthalmol- 2014-305327

9.     London Medicines Evaluation Network Review. Evidence behind change in treatment regimen recommendations and monitoring for ranibizumab and data on use in clinical practice for age related macular degeneration. September 2014.

10.  Academy of Medical Royal Colleges. The benefits of consultant-delivered care. London: AMRC, 2012.


Karen Goodall


Care UK, the UK’s largest independent healthcare provider, and Manchester Consultants Eye Partnership (MCEP), a local consultant consortium, together provide an NHS ophthalmology service for around 250,000 patients in Rochdale, England. The service delivers a full range of gold-standard secondary level activities in a community setting.