A systematic review of multimodal clinical biomarkers in the management of thyroid eye disease.

Thyroid Eye Disease (TED) is an autoimmune disease that affects the extraocular muscles and periorbital fat. It most commonly occurs with Graves' Disease (GD) as an extrathyroidal manifestation, hence, it is also sometimes used interchangeably with Graves' Ophthalmopathy (GO). Well-known autoimmune markers for GD include thyroid stimulating hormone (TSH) receptor antibodies (TSH-R-Ab) which contribute to hyperthyroidism and ocular signs. Currently, apart from radiological investigations, detection of TED is based on clinical signs and symptoms which is largely subjective, with no established biomarkers which could differentiate TED from merely GD. We evaluated a total of 28 studies on potential biomarkers for diagnosis of TED. Articles included were published in English, which investigated clinical markers in tear fluid, orbital adipose-connective tissues, orbital fibroblasts and extraocular muscles, serum, thyroid tissue, as well as imaging biomarkers. Results demonstrated that biomarkers with reported diagnostic power have high sensitivity and specificity for TED, including those using a combination of biomarkers to differentiate between TED and GD, as well as the use of magnetic resonance imaging (MRI). Other biomarkers which were upregulated include cytokines, proinflammatory markers, and acute phase reactants in subjects with TED, which are however, deemed less specific to TED. Further clinical investigations for these biomarkers, scrutinising their specificity and sensitivity on a larger sample of patients, may point towards selection of suitable biomarkers for aiding detection and prognosis of TED in the future.

Contribution of systemic factors on macular vessel density: a sex-specific population-based study.

PURPOSE: To evaluate the influence of systemic factors on macular vessel density in quantitative Optical Coherence Tomography Angiography (OCTA) by sex. STUDY DESIGN: A cross-sectional study. METHODS: A total of 2018 adults were recruited in this study. Participants were excluded (n=964) due to missing data, eye-related problems, or low OCTA scan quality. Macular vessel densities were measured with OCTA using split-spectrum amplitude decorrelation angiography algorithm. Only the data from the right eyes were selected for analysis. Multivariable linear regression analysis was performed to determine the associations between macular vessel density and obesity-related systemic factors in each gender group. RESULTS: The right eyes of 1054 participants (59.6% women) were enrolled. Men had significantly higher obesity parameters and associated risk factors. In multivariable linear regression analysis in men, older age and type 2 diabetes mellitus were independently associated with lower superficial retinal vessel density (ß = -0.37, p = 0.002; ß = -1.22, p = 0.03) and deep retinal vessel density, respectively (ß = -0.66, p < 0.001; ß = -1.76, p = 0.02); positive association was also observed between body mass index (BMI) and superficial retinal vessel density (ß = 0.56, p = 0.02). In women, only higher systolic blood pressure was independently associated with a lower deep retinal vessel density (ß = -0.50, p = 0.003). CONCLUSIONS: This large cross-sectional study shows that older age and type 2 diabetes mellitus are associated with lower superficial and deep retinal capillary vessel density in men. This may help clinicians better understand how systemic factors influence retinal vessel density in different genders and future studies can ascertain more potential sex differences.

Optic disc and peripapillary vessel density measured with optical coherence tomography angiography and its associations in Chinese adults: a large population-based study.

PURPOSE: To investigate the optic disc and peripapillary vessel density, as well as its ocular and systemic associations, in healthy eyes among adult Chinese population. METHODS: A population-based cross-sectional eye survey was conducted on Chinese adults residing in Hong Kong. 1891 eyes from 1891 participants who completed 4.5×4.5 mm optical coherence tomography angiography scans were recruited. Among the 1891 eyes, 404 were excluded due to low scan quality, optic disc or retinal disorders and non-Chinese ethnicity. The vessel densities (VDs) at nerve fibre layer plexus (NFLP) at both optic disc and peripapillary were collected for analysis. Multiple linear regression analysis was performed to determine the ocular and systemic associations of NFLP VD. RESULTS: The study included 1487 participants (men: 41.2%) with a mean age of 48.8±15.4 years. The mean NFLP VD of the whole en face image, inside disc and peripapillary region was 53.8%, 42.7% and 60.3%, respectively. In the multivariable model, decreased NFLP VDs were significantly associated with older age, male gender, longer axial length (AL) and lower Signal Strength Index. CONCLUSIONS: This large population-based cross-sectional study provided quantitative data of optic disc and peripapillary NFLP VD which may serve as a normative reference for clinical use. Apart from age, gender and AL, the scan signal strength also should be taken into consideration during the assessment of NFLP VD.