Axial spondyloarthritis: looking for the blind spot: Ocular manifestations and disease burden of axial spondyloarthritis

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease, related to the HLA-B27 gene, that mainly affects the sacroiliac joints and the spine. AxSpA is more prevalent in men, mostly develops between 20 and 40 years of age and is characterized by inflammatory back pain, fatigue and progressive limitations in spinal mobility. Patients suffer from chronic pain, loss of physical functioning, work absence and limitations in daily life. AxSpA can be accompanied by extra-articular manifestations, of which acute anterior uveitis (AAU) is the most prevalent. In addition, patients have an increased risk of atherosclerotic and non-atherosclerotic cardiovascular diseases. Currently, the most important treatment options for axSpA are non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy, and in case of insufficient response, Tumor Necrosis Factor alpha inhibitors (TNFi; a biologic) can be added. The first part of this thesis focusses at the disease burden of AxSpA in general. First, it demonstrates that the disease burden in axSpA is still considerable, despite the current treatment options. Importantly, it shows that female patients in Chile suffer a higher disease activity and burden, compared to men, and suggests this to be partly caused by inequality in treatment access, as female patients were less likely to use biologic treatment. Next, it describes a validation study of a performance-based test of physical functioning, which is an important disease outcome parameter of axSpA. This study demonstrated a high reliability, validity and feasibility of this test in Latin American patients. The second part of this thesis focusses on ocular manifestations of axSpA, particularly anterior uveitis. First, it confirms the important role of acute anterior uveitis (AAU) in the early recognition of axSpA, as referral of patients with chronic back pain and AAU from the ophthalmologist to the rheumatologist, resulted in a new axSpA diagnosis in 23% of the referred patients. This study demonstrated that in daily practice, the referral of patients with AAU and CBP can be improved, and results in the recognition of a high number of new axSpA patients. Second, it demonstrates how the TNF inhibitors (TNFi) golimumab and certolizumab, common treatment options for axSpA, also importantly reduce the recurrence of AAU in patients with axSpA. These studies show that golimumab and certolizumab, aside from reducing the axSpA disease activity significantly, also reduce the occurrence of anterior uveitis largely, in the first year of treatment by 80% (golimumab) and 87% (certolizumab). In a subsequent chapter of this thesis, we describe a study on whether axSpA patients show retinal vascular abnormalities, as a potential biomarker of cardiovascular disease. In this study, two retinal imaging techniques (fundus photography with Singapore I Vessel Assessment software, and Ocular Coherence Tomography Angiography) were used in axSpA patients between 50-75 years. This proof of concept study was the first to extensively study the retinal microvasculature in axSpA patients and showed a microvascular profile that has been associated with CVD in population studies. The last chapter focusses on the effects of structural collaboration between rheumatologists and ophthalmologists in the management of ocular inflammatory diseases, which consisted of a biweekly multidisciplinary meeting and an ophthalmology-dedicated rheumatology clinic. This work offers practical and valuable insights into how a collaboration can be beneficial for the management of these complex diseases. It emphasizes that it should provide easily accessible support for diagnostic work-up and guidance in the application of systemic immunosuppressives, in particular aimed to reduce the corticosteroid dosages. Overall, this thesis emphasizes that the disease burden in axSpA is still considerable and that improvement of the structural collaboration between rheumatologists and ophthalmologists is crucial to improve the awareness, early diagnosis and care of axSpA in patients with AAU.