Multicenter RCT of Eye-Brain Imaging in Diabetes Neurovascular Coupling

The measurement of Retinal Nerve Fiber Layer Thickness (RNFL) is crucial in ophthalmology. Its main parameter is RNFL thickness, which represents the overall average thickness across the entire measured retinal area and is a fundamental metric for initial assessment with a decrease often linked to optic nerve damage.The measurement is often obtained using optical coherence tomography (OCT), a non-invasive imaging technique that delivers high-resolution, cross-sectional images of the retinal layers.

Foveal Avascular Zone (FAZ) is a crucial parameter in retinal imaging, particularly for evaluating macular vascular integrity and diagnosing retinal vascular diseases, such as diabetic retinopathy. The key parameter is the FAZ area, which provides a detailed morphological and functional assessment of the foveal microvasculature. This measurement is commonly obtained using optical coherence tomography angiography (OCTA), which offers high-resolution, depth-resolved visualization of the retinal vasculature without the need for dye injection.

Visual Evoked Potential (VEP) is a neurophysiological technique used to assess the functional integrity of the visual pathway, from the retina to the visual cortex, by measuring the electrical activity generated in response to visual stimuli. Its main parameter is the latency of the P100 wave, which represents the time delay (in milliseconds) between the presentation of a visual stimulus and the peak of the positive waveform occurring around 100 milliseconds post-stimulus. VEP measurement is typically conducted using an electroencephalogram system equipped with specialized software for stimulus presentation and signal analysis, making it an essential tool for evaluating visual pathway integrity, diagnosing neurological disorders, and monitoring disease progression or treatment efficacy.

Gray matter volume (GMV) is a pivotal aspect in neuroimaging research, particularly focusing on the structural properties of the brain. A primary parameter in GMV measurement is the absolute volume, which quantifies the volume occupied by neuronal cell bodies, dendrites, and synapses within specific brain regions. This parameter offers crucial insights into brain development, aging, and the pathophysiology of neurological and psychiatric disorders. The GMV is commonly measured by magnetic resonance imaging (MRI) scanners, specifically high-field strength MRI systems that provide superior spatial resolution and contrast.

The Montreal Cognitive Assessment (MoCA) score is a widely used cognitive screening tool designed to detect mild cognitive impairment and early stages of dementia. It assesses multiple cognitive domains, including attention, executive functions, memory, language, visuospatial abilities, abstraction, calculation, and orientation. The MOCA scale will be downloaded from the official website (https://www.mocatest.org).The test consists of 30 items, with a maximum score of 30 points, and typically takes 10-15 minutes to administer. A score of 26 or above is generally considered normal, while scores below 26 may indicate cognitive impairment.The MoCA is administered by a trained clinician or researcher who scores the participant's performance based on standardized criteria, providing a comprehensive assessment of cognitive function.

The Mini-Mental State Examination (MMSE) score is a widely utilized cognitive screening instrument designed to assess cognitive impairment. It evaluates multiple cognitive domains, including orientation, memory, attention, language, and visuospatial abilities, through a series of questions and tasks. The MMSE will be downloaded from the official website at https://www.parinc.com.The MMSE, administered by a trained investigator, consists of 30 items, with a maximum score of 30 points, and typically takes 5-10 minutes to test. A score of below 24 often indicates cognitive impairment.

Symptom scores in Traditional Chinese Medicine (TCM) are a systematic approach to quantifying and evaluating clinical manifestations based on TCM theory. These scores, administered by a trained investigator, typically assess a range of symptoms, including but not limited to fatigue, pain, digestive issues, sleep disturbances, emotional states, and specific organ-related dysfunctions, through structured questionnaires or clinical observation. The degree can be scored from mild to severe.

Hemoglobin A1c (HbA1c) is a critical biomarker used to assess long-term glycemic control in individuals with diabetes, reflecting the average blood glucose levels over the preceding 2-3 months. The measurement of HbA1c include high-performance liquid chromatography (HPLC), immunoassay, and affinity chromatography, each offering high precision and accuracy.

Fasting Blood Glucose (FBG) is a fundamental test used to measure blood sugar levels after an individual has fasted for at least 8 hours. It is a key diagnostic tool for assessing glucose metabolism and identifying conditions such as diabetes mellitus, prediabetes, and insulin resistance.The measurement is performed using enzymatic methods, such as glucose oxidase or hexokinase assays, which provide high specificity and accuracy.

The SF-36 is a widely utilized questionnaire that measures health-related quality of life including physical functioning, bodily pain, general health perceptions, vitality, social functioning and mental health. It employs a standardized set of questions with weighted response options, enabling the quantification of an individual's health status thus serving as a valuable tool in clinical research, healthcare evaluation, and policy-making.

WBC measures the total number of white blood cells in the blood, reflecting the body's immune response. This is typically measured by collecting a blood sample from venous draw, and analyzed by using an automated blood analyzer.

RBC indicates the total number of red blood cells.The measurement involves drawing a blood sample from venous draw and using automated hematological analyzers or manual microscopic methods to count the number of red blood cells.

Hemoglobin is the iron-containing protein in red blood cells that carries oxygen. Its level is measured spectrophotometrically or by hemoglobinometers after collecting a blood sample, providing insights into the blood's oxygen-carrying capacity.

Packed Cell Volume measures the percentage of blood volume occupied by red blood cells. It is determined by centrifuging a blood sample to separate the red blood cells from the plasma and measuring the volume occupied by the packed red blood cells.

Platelet Count represents the number of platelets in the blood, essential for blood clotting, and low levels can cause bleeding tendencies while high levels may indicate inflammation or other disorders.

Neutrophil Count reflects the number of neutrophils, a type of white blood cell that plays a key role in fighting bacterial infections, and elevated levels often indicate an active infection or inflammation.

Lymphocyte Count measures the number of lymphocytes, another type of white blood cell involved in immune responses, particularly against viral infections, and changes in lymphocyte count can suggest immune system alterations or viral infections.

Urine pH measures the acidity or alkalinity of urine, crucial for reflecting the body's acid-base balance and the kidney's regulatory function. The normal range is generally between 4.6 and 8.0, with an average of 6.0. This test is conducted using urine analyzers or other methods, and deviations may indicate conditions such as diabetes, gout, acidosis, or frequent vomiting.

Urine protein detects the presence of protein in urine, which may indicate kidney disease or other underlying health issues.

Occult blood refers to the presence of RBCs in urine that is not visible to the naked eye but can be detected microscopically. This test is usually performed using fresh morning urine, and a positive result may suggest conditions such as urinary tract infections, stones, or kidney diseases.

Red blood cells in urine are detected through microscopic examination of the urine sediment. More than 3 RBCs per high-power field indicating hematuria. This may be due to kidney bleeding, urinary tract bleeding, or increased glomerular permeability.

White blood cells in urine are also identified via microscopic examination of the urine sediment. Elevated WBCs may indicate infection or inflammation, with normal levels being less than 5 WBCs per HPF.

Increased Urine ketones may suggest conditions such as diabetic ketoacidosis, hunger, excessive alcohol consumption, or vigorous exercise.

Creatinine is a metabolite produced by muscle metabolism and excreted by the kidneys. It serves as an important indicator of renal function.

eGFR is an estimation used to assess kidney function by calculating the rate at which the kidneys filter blood. It is derived from factors including serum creatinine levels, age, gender by using standardized formulas such as MDRD. The measurement provides an indication of renal function and aids in the diagnosis and management of chronic kidney disease. Lower eGFR values indicate decreased kidney function.

AST is an enzyme found in multiple tissues, including the liver, heart and skeletal muscle. Elevated AST indicates liver damage.

ALT is an enzyme predominantly found in liver cells and is involved in protein metabolism. Elevated ALT indicates liver damage.

GGT is an enzyme found in the liver and biliary system, and its level is used to detect bile duct issues or liver damage.

The QT interval on 18-lead electrocardiogram（ECG）represents the total duration of ventricular depolarization and repolarization, measured from the beginning of the QRS complex to the end of the T wave.The prolongation of the QT interval may be correlated with drug-induced severe arrhythmias, notably including Torsades de Pointes, thereby making the QT interval one of the key indicators reflecting drug safety.