Ocular Manifestations of Granulomatosis With Polyangiitis.

The current state of knowledge on ANCA-associated vasculitis (AAV) indicates that it is a group of autoimmune diseases in which small blood vessels in various organs are affected. Disease entities included in this group are granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome).

These are rare diseases, with an incidence in Europe of approximately 20-25 cases per million people per year. There is a slight predominance among men, and the risk of developing the disease increases with age.

ANCA antibodies play a role in the pathogenesis of the disease, and inflammation within small vessels leads to damage of the vessel walls, resulting either in rupture or occlusion of the vessel lumen. Consequently, vital organs such as the kidneys, lungs, heart, nervous system, upper respiratory tract, gastrointestinal tract, and eyes may be affected.

If the disease is not diagnosed, untreated, or treated improperly, it can lead to irreversible failure of these organs and even death. Despite appropriate treatment, AAV diseases tend to relapse; therefore, therapy consists of two phases: induction therapy and maintenance therapy.

Current EULAR/EDTA guidelines for induction treatment of AAV recommend the use of cyclophosphamide (CYC) or rituximab (RTX) in combination with glucocorticosteroids in cases of severe disease. If remission is achieved after induction therapy, maintenance treatment should be initiated with drugs such as azathioprine, mycophenolate mofetil, methotrexate, or rituximab, combined with a low dose of glucocorticosteroids. Maintenance therapy should last no less than two years.

The study will focus on ophthalmological evaluation of patients diagnosed with ANCA-associated vasculitis. In this disease, all structures of the eye may be involved. The most common ocular manifestations include scleritis, keratitis, proptosis, inflammation of orbital tissues, nasolacrimal duct obstruction, and orbital involvement leading to proptosis, double vision, and restricted eye movement.

Until recently, the disease was often fatal. However, advances in diagnostics and current pharmacological treatment options, combined with appropriately aggressive immunosuppressive therapy, have significantly improved survival, enhanced patients' quality of life, and reduced mortality. Early diagnosis and prompt initiation of appropriate therapy are crucial.

In the literature there are no available data on the prevalence in our country regarding the frequency of involvement of ocular structures in this disease, and there is little information on the nature of the changes or treatment outcomes. Based on data from other populations in these rare disorders, all ocular structures can be affected. The most common ocular manifestations include scleritis, keratitis, proptosis, orbital tissue inflammation, nasolacrimal duct obstruction, orbital involvement with proptosis, diplopia, and restricted ocular motility.

For the study, patients referred for ophthalmologic consultation from the Nephrology Clinic of the Military Institute of Medicine with newly diagnosed or relapsing ANCA-positive vasculitis will be enrolled. Estimated number of patients: 60. Examinations will be performed for initial ophthalmic evaluation. If more frequent visits are required (whenever ophthalmic involvement is present), additional follow-ups will be scheduled as clinical status requires. The study is planned for a minimum duration of three years.

Ophthalmic examinations will include: visual acuity, intraocular pressure, and anterior and posterior segment examinations. Depending on the clinical situation and reported symptoms, additional tests will be performed:

* anterior or posterior segment OCT
* neurological assessment - pupillary light reflexes, visual field, color vision
* exophthalmometry, ocular motility testing
* fluorescein angiography
* photographic documentation
* imaging studies Collected data will be subjected to statistical analysis.

OCT angiography will be performed to assess whether changes in small vessels influence the vasculature of critical structures for vision in comparison to healthy individuals.

• Optical coherence tomography angiography (Diagnostic test): standardized OCTA protocol for macula 3x3 standardized OCTA protocol for optic disc 4.5x4.5

Primary outcomes

• Statistical analysis of ocular structures involvement [from 01/2024 until 12/2026]: Based on data from other populations in these rare disorders, all ocular structures can be affected. The most common ocular manifestations include scleritis, keratitis, proptosis, orbital tissue inflammation, nasolacrimal duct obstruction, orbital involvement with proptosis, diplopia, and restricted ocular motility. The epidemiology data will be collected and presented in percenage data

Secondary outcomes

• Vessel structure and density measured with OCT angiography compared to control group. [1/2024-12/2026]: Each patient will have assessment of vessels structure and vessel density in macula and optic disc according to standardised protocols. The data will be compared to normative data in healthy controls.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

ANCA positive vasculitis age 18- no limit patients with onset od the disease and patients already under treatment

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Exclusion Criteria:

* no consent for ophthalmic examination
* inability to udergo ophthalmic examination

• Byszewska A, Skrzypiec I, Rymarz A, Niemczyk S, Rekas M. Ocular Involvement of Granulomatosis with Polyangiitis. J Clin Med. 2023 Jul 2;12(13):4448. doi: 10.3390/jcm12134448. PMID 37445483