When should AMD treatment stop?

December 1, 2012

Study identifies factors for discontinuing Lucentis treatment and helps streamline AMD services

Age-Related macular degeneration (AMD) is the leading cause of severe loss of vision in the elderly population in the developed world, affecting 30–50 million people worldwide.1 It is estimated that a quarter of a million older adults in the UK alone suffer from blindness due to this condition.2

The current treatment for wet AMD, approved by NICE, is ranibizumab (Lucentis, Novartis, Basel, Switzerland).4 Treatment initiation with three consecutive monthly injections, followed by continued monthly injections, has provided the best visual-acuity outcomes in pivotal clinical trials. If continued, monthly injections are not feasible after initiation, a flexible strategy appears viable with monthly monitoring of lesion activity recommended.5

As there are no clear guidelines for stopping antiVEGF treatment in these patients, a national protocol to discontinue treatment is still awaited. We hope that this study will further enable us to identify those factors for discontinuing such treatment and benefit streamlining of AMD services.

Current AMD guidelines

In regards to discontinuation of on-going treatment with intravitreal Lucentis, NICE (National Institute of Clinical Excellence, UK) Technology Appraisal 155 (August 2008; modified May 2012)4 states that treatment with ranibizumab should be continued only in people who maintain adequate response to therapy. They also state that criteria for discontinuation should include persistent deterioration in visual acuity and identification of anatomical changes in the retina that indicate inadequate response to therapy. They recommend that a national protocol specifying criteria for discontinuation is developed.

In its Age-Related Macular Degeneration Guidelines for Management (February 2009),7 The Royal college of Ophthalmology state in their guidelines to consider discontinuing treatment permanently if any of the following criteria are met:

1. A hypersensitivity reaction to ranibizumab is established or suspected. A change to pegaptanib or PDT is recommended.

2. Reduction of BCVA in the treated eye to less than 15 letters (absolute) on 2 consecutive visits in the treated eye, attributable to AMD in the absence of other pathology.

3. Reduction in BCVA of 30 letters or more compared to either baseline and/or best recorded level since baseline as this may indicate either poor treatment effect or adverse event or both.

4. There is evidence of deterioration of the lesion morphology despite optimum treatment. Such evidence includes progressive increase in lesion size confirmed with FFA, worsening of OCT indicators of CNV disease activity or other evidence of disease activity in the form of significant new haemorrhage or exudates despite optimum therapy over 3 consecutive visits.

In patients under long-term hospital follow up, the Royal College of Ophthalmology recommends their discharge from follow up in the following circumstances:

1. The decision to permanently discontinue ranibizumab has been made.

2. There is no evidence of other ocular pathology requiring investigation or treatment.

3. There is low risk of further worsening or reactivation of wet AMD that could benefit from restarting treatment (e.g., very poor central vision and a large, non-progressive, macular scar).

Aim

Using the above guidelines, this study aimed to identify putative factors, which indicate a poor response to treatment of wet AMD by ranibizumab. This would facilitate the formulation of departmental protocols related to discontinuing treatment permanently and discharging patients from the AMD service. By doing so, it would not only avoid unnecessary treatment and its potential complications but also enable better use of clinical resources in terms of cost reduction and increasing clinical potentials in an environment of financial constraints currently faced by most NHS hospitals.

Methods

We gathered retrospective data from the list of patients who were treated with intraviteal Lucentis for wet AMD between 2008 and 2011 at The Ipswich Hospital NHS Trust. Visual acuity was recorded on a Logmar chart. Patients who had a pretreatment visual acuity (VA) worse than 1.2 or anyone noted to have VA worse than or equal to 1.2 on two consecutive visits were included. Wet AMD patients with only one recording of VA 1.2 or worse were excluded on grounds of observer bias. Data was recorded in a pre-designed proforma.