Short summary

This is a cross-sectional study of non-invasive retinal markers in patients with sarcoidosis. We aim to demonstrate if non-invasive structural and metabolic retinal markers will differ according to primary site of disease affection and if there is a connection between retinal changes and blod cytokines, chemokines and microRNA profile. 

Rationale

Sarcoidosis is a multisystem inflammatory granulomatous disorder of unclear etiology. It is often characterized by intrathoracic involvement which may be demonstrated by chest radiographic imaging as bilateral hilar lymphadenopathy and pulmonary infiltration, but it may also involve other organs such as skin, joints, eyes and the central nervous system (CNS). Ocular involvement is common and has been demonstrated in up to every second patient. The basic diagnostic criteria for sarcoidosis include a histopathological verification of non-caseating epithelioid cell granulomas, and exclusion of other diseases with granuloma formation. However, in cases where ocular sarcoidosis is the only manifestation or where ocular manifestation precedes systemic manifestation diagnosis can be hard to verify, due to the risk of vision loss linked to intraocular biopsy. 

The vascular tree is the only part of the human body available for direct, non-invasive, in-vivo structural and metabolic inspection. 

Wide-field retinal imaging is to be used for measuring the retinal vascular structure which includes vascular measurements like calibers, fractals and more advanced markers of vascular dysfunction like vascular tortuosity and suboptimal vascular branching. 

The metabolic changes are assessed on the basis of lower retinal oxygen consumption as given by a higher retinal venular oxygen saturation. 

Optical coherence tomography (OCT) provides a high-resolution, cross-sectional image of more than 18 different retinal and choroidal layers. Hence retinal thinning can be evaluated as a potential marker of neurodegeneration as previously demonstrated in diabetes. 

In a cross-sectional study including patients with a history of sarcoidosis, we aim to demonstrate if non-invasive structural and metabolic retinal markers will differ according to primary site of disease affection. 

In particular, we hypothesize to demonstrate: 

a) Retinal structural alterations (caliber narrowing and suboptimal vascular branching) in patients with ocular sarcoidosis

b) Retinal structural neurodegeneration in patients with CNS-involvement and ocular sarcoidosis.

c) Retinal metabolic changes in patients with ocular sarcoidosis. 

d) The connection between retinal metabolic and structural changes and blood cytokines, chemokines and microRNA profile. 

Proof-of-concept has been established that non-invasive retinal markers are in association and is sometimes even predictive of ocular and extra-ocular manifestations of systemic disease

We will be the first to test if non-invasive structural and metabolic retinal markers are linked to ocular and systemic disease in sarcoidosis. If demonstrated, this may lead to an earlier diagnosis and a better individualized management of the disease.  

Description of the cohort

The cohort consists of 100 patients with the diagnosis sarcoidosis. The cohort i subdivided into 4 groups by primary site of disease affection: 1) patients with advanced sarcoidosis, 2) ocular sarcoidosis, 3) patients with primary CNS involvement and 4) patients with primary lung or joint involvement. 

Data and biological material

From each participant 25ml blood will be collected for biobank and latter analysed for cytokines, chemokines, mikroRNA and DNA.

Blood sampling of circulating biomarkers including pro- and anti-inflammatory cytokines and neurofilament.

DAS28CRP will be calculated from CRP, sarcoidosis markers and the antibody profile.

4 surveys will be filled out: Quality of life questionnaire21, Short Form 36 Health Survey, HAQ, and Charlson comorbidity index. 

Demographic data as well as systemic disease evaluation, previous blood samples, scan results and biopsy results, previous immunosuppressive treatment and comorbidity. If it is clinically relevant, the participant will be referred to a new x-ray of the chest and lung-function test.

Ocular examination with best corrected visual acuity, mydriatic slit-lamp examination and funduscopy with classification of potential uveitis (IWOS criterias and SUN). Intraocular preassure. 

Wide-field retinal imaging, enhanced depth imaging spectral domain optical coherence tomography and retinal oximetry. 

Collaborating researchers and departments

Department of Ophthalmology, Odense University Hospital 

• Head of the Research Unit of Ophthalmology, Professor Jakob Grauslund
• Professor, Jimmi Wied

Department of Rheumatology, Odense University Hospital 

• Staff Specialist, Keld-Erik Byg 
• Head of Research Unit of Rheumatology, Professor Torkell J Ellingsen 

Department of Clinical biochemistry and pharmacology