Assessing the benefit of Ranibizumab treatment for Age- related Macular Degeneration: A follow-up

Project: Other projectResearch collaboration

Project Details


Our research constitutes the latter stages of a longitudinal study investigating the long-term effects of anti-angiogenic treatments (periodic Ranibizumab injections) on the symptoms of neovascular (or ‘wet’) Age-Related Macular Degeneration (AMD), and the ensuing functional and structural changes to the visual areas of the brain. This is a follow-up to a previous project investigating changes from baseline (diagnosis/before treatment), with monthly followups for 3 months during the treatment initiation phase.

Wet AMD is a more treatable, but less common form of late stage Macular Degeneration. It is characterised by the growth of fragile blood vessels underneath the macula, and the resultant retinal scarring and exudation of blood, lipids, and liquid into the retina. As the scarring and leaking of fluid continues, a blind-spot is formed in the central visual field, known as a scotoma. Hernowo et al. (2014) showed that patients with a central scotoma had noticeable volumetric reductions in brain areas corresponding to the visual field occupied by the scotoma (the lesion projection zone), spreading as the scotoma grew. Nevertheless, evidence suggests that these areas can become responsive again as retinal function is restored (Baseler et al. 2011). We will therefore begin by exploring the extent to which seven-year long treatment of Wet AMD stabilises and/or reduces the growth and size of central scotoma. This will be done using MRI and fMRI, with the aim of comparing both brain structure and function of patients in response to stimulation of the treated and untreated eye, replicating the methodology previously applied to the same patients. More specifically, the procedure will involve presenting full-field light stimuli to patients inside the scanner to determine the areas of the primary visual cortex that show a high haemodynamic response. Subsequently, this data will be combined with measures of microperimetry, visual acuity and fixation stability to give a measure of each participant’s visual field, and the structure and function of the corresponding visual areas. Additionally, we will be applying this procedure to age matched controls with normal vision, enabling further comparison.

Layman's description

Age related macular degeneration (AMD) is the leading cause of blindness in the UK. The disease progressively destroys vision from the centre of vision to the periphery over time. We use the centre of our vision to see in fine detail, an ability that is essential for reading. AMD principally affects the elderly and comes in two main forms. The form that progresses rapidly is known as wet AMD for which there are treatments including Lucentis (Ranibizumab) and Eylea (Aflibercept). The other form progresses more slowly and is known as dry AMD. There is, as yet, no treatment for dry AMD. The aim of this follow-up study was to assess the visual benefits that result from the long-term treatment of wet AMD. Research has shown that patients benefit by being able to read more of the standard letter chart, which is often used to assess vision. We wanted to determine how vision improves across the whole visual field which requires different tests to the letter chart. One test we applied is a visual field test, which
measures vision by presenting small spots of light at different locations in the visual field. The other test was a brain scan, which shows how much of the brain receives information from the eyes. We performed these tests and compared results with the initial study to see how well long-term treatment was working.

Key findings

Main findings
All analyses were completed on a cohort of 7 patients who took part in the original and follow-up study. Of the original 10 patients, 1 withdrew following consent to the follow-up, 1 declined to take part and 1 was deceased. A significant volumetric decrease was found in the entire occipital cortex after long-term treatment (p = 0.023), primarily due to reduced cortical thickness of the occipital pole (p = 0.027) rather than the calcarine sulcus (p = 0.174). A linear regression revealed that changes in the entire brain (excluding the occipital lobes) largely explained variance observed in the calcarine sulcus (65%, p = 0.029) but did not fully account for reductions in the occipital pole (31.6%, p = 0.189). Clinical assessments revealed increased visual acuity during treatment initiation, decreasing slightly with long-term treatment (n.s). Central retinal thickness initially decreased, with signs of stabilisation following long-term treatment (n.s). Retinal sensitivity measured with microperimetry increased with long-term treatment (n.s). Visual acuity improvements following treatment were maintained above pre-treatment levels over the long term, whilst central retinal thickness showed stabilisation and retinal sensitivity increased. Nevertheless, long-term anti-VEGF treatment did not prevent significant atrophy of primary visual cortex (V1) in representations of the retinal regions affected in nvAMD. This study provides a hypothesis about the potential role of visual cortex in long-term vision loss in patients treated for nvAMD.

This work is currently being prepared for submission to the journal BRAIN. Dissemination via poster has also been presented to the annual Association for Research in Vision and Ophthalmology (ARVO) conference in April 2018.

Feedback to participants: A meeting is to be arranged with all participants who took part in this study whereby a verbal summary of the findings will be provided.
Short titleComplete Picture 2
Effective start/end date15/03/176/11/17