Role of diabetic retinopathy including chorioretinal microvasculature and diabetic neuropathy including neuroinflammatory biomarker on cognition and visual perception in type II diabetes mellitus

**Title of the project:**Role of diabetic retinopathy including retinal microvasculature and diabetic neuropathy including neuroinflammatory biomarker on cognition and visual perception in type II diabetes mellitus

Aim:

To study the role of diabetic retinopathy including retinal microvasculature and diabetic neuropathy including neuroinflammatory biomarker on cognition and visual perception in type II diabetes mellitus

Objectives:

1.     To find the cognition and visual perception in individuals with type II diabetes mellitus, diabetic retinopathy and diabetic neuropathy

2.      To explore the correlation of cognition with visual perception in type II diabetes mellitus, diabetic retinopathy and diabetic neuropathy

3.     To understand the relationship between retinal microvasculature and cognition, visual perception in type II diabetes mellitus, diabetic neuropathy, and diabetic retinopathy

4.     To evaluate the relationship between change in cognition and visual perception in type II diabetes mellitus, diabetic retinopathy and diabetic neuropathy using neuroinflammatory biomarkers

Justification for study:Diabetes is the second leading disease in India. The majority of older adults are at high risk for T2DM. Hyperglycemia is an important risk factor for developing a microvascular complication. Several studies have investigated the potential impact of diabetic complications on cognitive function. Limited studies have been done on visual perception. There are limited studies on the Indian population to study the cognition and visual perception among T2DM. Most of the previous studies have less sample size, did not study each cognitive domains and did not measure visual perceptual skills in type 2 diabetes mellitus patients. Using MVPT-V perception skills were assessed but normative data was not available for older adults and also different groups have not been compared to see how these functions are affected in diabetic neuropathy and retinopathy. Studied on RNFL thinning, photoreceptor, and ganglion cell loss but the relationship between retinal microvasculature, cognition, and visual perception with human plasma markers in T2DM has not been studied. This research will help us to better understand the underlying mechanisms and relationship between plasma biomarkers, retinal neural and vascular changes, visual perception, and cognitive function in Type 2 DM. This knowledge will enable us to improve testing and improve clinical management strategies, and ultimately enhance the quality of life for individuals living with these complications.

Procedure: The study will be initiated after getting approval from the Institutional Protocol Approval Committee (IPAC) and Institutional Ethical Committee. Followed by CTRI registration will be done. The study will be performed on type 2 diabetes mellitus with the age range from 40-80 years. Patients who are coming to the hospital outpatient department and will go through the comprehensive eye examination based on the diagnosis made by the ophthalmologist and physician and who will meet our criteria will be included in the study. Consent will be taken from participants and the patient information sheet will be given to all before conducting the study. Detailed demographic data including age, gender, educational levels, detailed history to rule out any other systemic associations, duration of the disease, current medications, HbA1c values, fasting blood sugar (FBS) levels, post prandial blood sugar (PPBS) levels, blood pressure, routine eye examination findings, and disease diagnosis will be noted. There are 4 groups, age-matched normal (Nondiabetic), Type II diabetic mellitus, diabetic retinopathy, and diabetic neuropathy. All 4 groups will be examined for selection criteria. To rule out neurological disorders, a detailed history will be taken with past medical consultations & medications, and a neurological examination will be done. DR will be diagnosed by the retina specialist by comprehensive eye examination including fundus evaluation. DN will be diagnosed with a detailed examination which includes Vibration Perception Threshold (VPT), small nerve assessment using hot and cold perception, and monofilament test. All measurements will be taken on a single visit. MoCA questionnaire will be used to evaluate cognitive function. It consists of 30 points. The time needs to administer the test will be around ten minutes. An overall score of ≥ 26 will be considered normal. The MVPT- 4 is the latest revision used to evaluate visual perceptual skills among adults. The MVPT-4 includes a variety of tasks which consist of 45 items, and it takes 20-30 minutes to complete the whole test. A number of errors counted and subtracted from the total plates and raw score will be noted. Retinal nerve fibre layer thickness in µm will be taken from the optical coherence tomography (OCT). Followed by OCTA will be performed for vessel density in percentage, foveal avascular zone area in mm2, and avascular density in percentage. All participant’s Blood will be collected as per the aseptic precautions serum will be separated, and stored at -80 degrees in the freezer until analysis. Human blood biomarkers will be analyzed using the ELISA method.  Values of human blood biomarkers which are Neurofilament light chain (NFL), Glycated Haemoglobin, lipid profile, C-Peptide will be noted.