Introduction
A biomarker is a biological characteristic of the body that is measured and evaluated and gives an insight into health levels. Various types of molecules, such as DNA, proteins, and hormones, act as biomarkers and indicate the assessment of health conditions. It serves as an indicator of biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.
What Is an Ocular Biomarker?
These are molecular biomarkers concerning ophthalmology. Ocular biomarkers help in the early detection and prediction of disease. It also reveals the severity and rate of progression of the disease. The treatment response is also recorded with the help of these molecular biomarkers.
What Is the Importance of Ocular Biomarkers?
- Biomarkers provide a measurable algorithm for the evaluation of disease progression.
- Ocular biomarkers help in the early diagnosis of disease.
- Identification of risk factors and early signs of the disease at the preclinical stage.
- To evaluate the effectiveness of various treatments.
- Detection of ocular biomarkers is minimally invasive.
- It overcomes the limitations of eye care.
- The potential biomarkers exist on the ocular surface, thus easily available resources for research and discovering biomarkers.
What Are the Various Ocular Biomarkers?
- Eye Tear:
- A tear contains more than five hundred proteins, and apart from its role on the ocular surface, a tear remains an untapped reservoir for potential biomarkers. The application of various techniques like enzyme-linked immunosorbent assay (ELISA), anterior segment OCT, and functional slit lamp biomicroscopy.
- Meibomian Gland:
- Meibomian glands are sebaceous glands along the rims of the eyelid. They secrete an oily substance called meibum, that prevents the evaporation of tear film and thereby prevents dry eyes.
- The evaluation of the functioning of the meibomian gland is assessed by techniques called infrared meibography and cellular level assessment by in vivo confocal microscopy (IVCM).
- IVCM techniques assess various parameters that act as biomarkers. They are meibomian gland orifice width, short diameter, long diameter, and density. These parameters help in the diagnosis of meibomian gland dysfunction.
- Conjunctiva:
- Conjunctiva is a transparent, highly vascularized mucous-secreting tissue of the eye.
- In vivo, confocal microscopy evaluates several changes in the cornea and conjunctiva. It is a non-invasive procedure for the diagnosis of dry eye diseases.
- HLA-DR is a glycoprotein normally expressed in conjunctival epithelial cells, which is used to monitor the severity of the disease and evaluate the treatment effect in dry eye disease.
- Goblet cells present in the conjunctival epithelial layer secrete mucin into the ocular surface. Decreased density of goblet cells results in dry eye and other ocular surface inflammatory diseases like Steven-Johnson syndrome, and ocular mucous membrane pemphigoid.
- The expression of histamine biomarkers plays an important role in ocular allergy.
- Increased levels of eotaxin -2 in ocular surfaces are common in ocular allergies.
- Paired box protein in the ocular surface is a potential biomarker. This is a protein commonly expressed from the cornea, limbus to the conjunctiva. The level of paired box protein is significantly reduced in Sjogren syndrome and high chance of ocular staining.
- The level of small proline-rich protein is associated with ocular damage, and the level of protein is elevated in the Sjogren syndrome.
- NAMPT - nicotinamide phosphoribosyltransferase, also called visfatin, is a proinflammatory cytokine. It is identified as one of the genes that have the greatest potential as a biomarker. High expression of this protein is associated with low tear production, ocular surface damage, and tear film instability.
- T lymphocytes have an active role in the inflammation of the anterior part of the eye.
- Lipid peroxidation markers are other biomarkers used to detect oxidative damage. this biomarker can be used to assess the severity of dry eye diseases.
- Conjunctival epithelial proteomes are inflammatory and apoptotic biomarkers to know the role of conjunctival proteins in disease pathophysiology.
Which Are the Ocular Biomarkers for Alzheimer’s Disease?
Alzheimer's disease is a brain disease that causes changes in the brain, causing brain cells to shrink and eventually die. Alzheimer's disease causes a gradual decline in memory, behavior, and social skills. The ocular biomarkers are
- Retina and Optic Nerve: The retina is a neurosensory tissue in the interior of the eye. The retina contains photoreceptor cells and helps send signals to the brain via the optic nerve to process the image. The neurosensory retina is considered to be a direct extension of the brain. The changes in the neurosensory layer are seen in the retinal tissue. In Alzheimer's disease, neurodegenerative changes appear in the retinal tissue. The important pathological signs of Alzheimer's are amyloid beta protein and neurofibrillary tangles, which were identified in the retina. Higher levels of amyloid beta protein confirmed Alzheimer's disease. Thus, amyloid beta protein is an important biomarker for the early detection of Alzheimer's disease.
- Optical Coherence Tomography: This technique utilizes retinal imaging for the assessment of Alzheimer's disease. OCT uses light waves to get high-resolution cross-sectional images of the retina. In Alzheimer's patients, the retinal tissue density is high throughout multiple layers. Another biomarker in Alzheimer's disease prediction is choroidal thickness. The choroidal thinning is correlated with the deposition of amyloid beta protein.
- Vitreous Humor: It is a transparent gelatinous substance in the posterior part of the eye that helps maintain the shape of the eye. Vitreous humor is used as an ocular biomarker to track degenerative changes such as Alzheimer's disease.
- Lens: The human lens has one of the highest concentrations of protein, and the degenerative changes cause the accumulation of protein in the lens. The presence of amyloid beta protein can result in cataract formation and is a biomarker for Alzheimer's disease.
- Pupil and Cornea: The decreased corneal sensation and increased dendritic cell density act as ocular biomarkers in Alzheimer's disease. The atypical pupillary response to cholinergic antagonists and increased pupillary size are seen in Alzheimer's disease.
What Are the Challenges and Opportunities Related to Ocular Biomarkers?
Biomarkers are widely used in clinical trials, in understanding disease pathogenesis, and in the assessment of patient response to treatments. The FDA-approved ocular biomarker tests are InflammaDry and Advanced Tear Diagnostics. The ocular matrices are sampled in human clinical trials. Regarding the collection of the samples, tears, aqueous humor, and vitreous humor shows a great challenge. So the collection of aqueous and vitreous humor is very limited due to the invasive procedure. Also, pose an additional risk for ocular surface damage. Biomarker evaluation has been a great advantage in the study and diagnosis of various diseases.
Conclusion
Biomarkers present in the human body are used in the assessment of various disease parameters. Ocular biomarkers provide valid information about the presence of disease, the severity of the disease, and prediction chances of diseases and help in the evaluation of the therapeutic responses.
