New approach to improve treatment for leading cause of blindness
Age-related macular degeneration (AMD) is expected to affect almost 288 million people worldwide and almost 25 million Europeans by 2040. Of those suffering from vision loss, the vast majority will be suffering from wet AMD. Vascular endothelial growth factor (VEGF) is the major contributor in the development of the abnormal and leaky choroidal blood neovessels, leading to severe loss of central vision. Ten years ago, therapies involving anti-VEGF proteins revolutionised the treatment of wet AMD. Treatment consists of regular injections of the anti-VEGF drugs into the vitreous humour of the eyeball, possibly for the rest of the patient’s lifetime. It slows down the development of these abnormal blood vessels. However, the dosing interval varies widely among the patients and is shorter in clinical trials than in clinical practice. The injection frequency is decided by the ophthalmologist, based upon the subjective analysis of retina images obtained from optical coherence tomography (OCT). However, there is no quantitative method available for its evaluation. Assessing the concentration of the drug in the eye (pharmacokinetics (PK)), and its impact on the condition (pharmacodynamics (PD)), has been challenging. Support from the Marie Skłodowska-Curie Actions programme to the EyeTREAT project enabled lead researcher Eva del Amo Páez to develop a new way of assessing frequency needs. “The advantage of our approach is that we can use available, non-invasive imaging data to build the model,” says del Amo Páez. She conducted her research at the University of Manchester, supervised by Leon Aarons, professor of Pharmacometrics. EyeTREAT has developed a way of using data from OCT, which is a non-invasive imaging technique used to scan the retina. OCT scanning is routine practice in the ophthalmological clinics to aid macular degeneration diagnosis. Quantitative data of central retinal thickness can be extracted from the non-invasively OCT retina scans and is used to assess PD, and, knowing the dose and frequency of injections of the anti-VEGF drug, the PK can be estimated. Using a modelling technique called ‘nonlinear mixed-effects’, EyeTREAT has managed to gain insights into the impact of the injections across a patient population despite the fact that individual data is sparse. In doing so, EyeTREAT has managed to establish preliminary population PKPD models to understand the link between treatment and effect. “Current scarce models involve invasive anterior humour sampling from the anterior chamber of the eye. The advantage of our approach is that we can use available, non-invasive imaging data to build the model,” explains del Amo Páez. These models could shine some light on variability attributed to intrinsic patient factors, such as gender and age, and dosing regimen selection for effective treatment. Work done as a result of EyeTREAT’s research can facilitate future models for other anti-VEGF drugs. Other retinal diseases involving neovascularisation at the back of the eye, such as retinal vein occlusion and diabetic retinopathies, could also benefit. While del Amo Páez is still analysing the data, she explains: “We have observed that there is a correlation between the initial status of the central retina thickness and the efficacy of the treatment. Further studies, with larger patient data and more frequent OCT measurements, are needed to define the appropriate individualised dosing regimen of these patients in clinics.” Once established, the ophthalmologist could anticipate the injection interval from the individual retina scan determination with OCT.
Keywords
EyeTREAT, age-related macular degeneration, AMD, vascular endothelial growth factor, retina scans, VEGF, anti-VEGF
