**Background:** The eye is a complex sensory organ that contains a wealth of physiological information and biomarkers accessible through ocular fluids like tears, aqueous humor, and vitreous humor. These biomarkers can be used for point-of-care diagnosis and management of various diseases, including ophthalmic conditions (glaucoma, retinitis pigmentosa, age-related macular degeneration), metabolic diseases (diabetes, hyperlipidemia, gout), and neurodegenerative diseases (Parkinson's, Alzheimer's, multiple sclerosis). Wearable ophthalmic devices, particularly smart contact lenses (SCLs), offer a noninvasive platform for continuous monitoring and therapy. This review provides a comprehensive overview of the anatomy and physiology of the eye, the biomarkers relevant to disease, the technologies enabling SCLs, and the current state of diagnostic and therapeutic SCLs, as well as other ocular devices like retinal prostheses and optogenetic approaches.
**Methods:** This is a narrative review that synthesizes information from a wide range of published literature. The authors first describe the anatomy and physiology of the eye, including the structure of the cornea, sclera, retina, and the composition and dynamics of tears, aqueous humor, and vitreous humor. They then detail the pathophysiological mechanisms of various diseases that can be managed through the eye, such as glaucoma (focusing on intraocular pressure, glutamate toxicity, inflammatory factors, and oxidative stress), photoreceptor degeneration (retinitis pigmentosa and age-related macular degeneration), metabolic diseases (diabetes, hyperlipidemia, gout, hyperkalemia), and neurodegenerative diseases (Parkinson's, Alzheimer's, multiple sclerosis). The review then provides an extensive overview of the technologies used in SCL fabrication, including materials (conductive, polymeric, metal-organic, optical), fabrication techniques (photolithography, soft lithography, printing, electrospinning, sol-gel), powering methods (wireless power transmission, biofuel cells, supercapacitors, solar cells, flexible batteries), and data transmission methods (NFC, RFID, Bluetooth, Wi-Fi). Finally, the review categorizes and describes diagnostic SCLs (electrochemical, physical, electrophysiological, optical) and therapeutic SCLs (drug delivery, heat therapy, optical therapy, electrical stimulation), and discusses retinal prostheses and optogenetics as other therapeutic modalities.
**Key Results:** The review presents a vast amount of data from numerous studies, but as a narrative review, it does not present a single set of experimental results. Key findings summarized include:
- **Biomarkers in Tears:** Tear glucose levels reflect blood glucose levels with a time delay of around 10 min. Cholesterol levels in tears correlate with blood cholesterol levels in rabbits. Alpha-Synuclein (α-Syn) levels in tears are altered in Parkinson's disease patients: oligomeric α-Syn increased by 8.6-fold (4.43 ± 1.26 ng mg⁻¹ tear protein) in early-stage PD. A combination of four proteins (lipocaline-1, lysozyme-C, lacritin, and dermcidin) are effective biomarkers for Alzheimer's disease.
- **Diagnostic SCLs:** A graphene-based glucose sensor showed a response time of ~1.3 s and a minimum detectable concentration of ~12.57 μM. A MoS₂-FET glucose sensor showed 48% sensitivity at 0.6 mM glucose. An MMP-9 sensor had a limit of detection (LOD) of 0.74 ng mL⁻¹. A cortisol sensor had an LOD of 10 pg mL⁻¹. An IOP sensor using a strain gauge on a rigid-soft hybrid layer showed a sensitivity of 0.05% per mmHg. A capacitive IOP sensor with a pyramid-microstructured dielectric layer showed a sensitivity of 1.101‰ mmHg⁻¹.
- **Therapeutic SCLs:** A drug delivery system using a gold channel dissolved at 1.85 V with an operation current of 5–9 μA. A phototherapeutic contact lens with red ILEDs maintained a safe temperature of 37 °C. An electrical bandage contact lens promoted complete healing of corneal wounds in rabbits after 3 days.
- **Retinal Prosthesis:** The Argus II epiretinal prosthesis was the first to receive CE marking. The Alpha IMS subretinal implant has 1,500 independent photodiode-amplifier-electrode units and achieved a best visual acuity of 20/546. A photovoltaic subretinal prosthesis with 70-μm-wide pixels achieved a spatial resolution of 64 ± 11 μm in rats.
**Clinical Implications:** The review highlights the significant potential of SCLs to revolutionize disease management by enabling noninvasive, continuous, and real-time monitoring of a wide range of biomarkers. This could lead to earlier diagnosis, personalized treatment, and improved patient outcomes for conditions like glaucoma, diabetes, and neurodegenerative diseases. Therapeutic SCLs offer the possibility of targeted drug delivery, heat therapy, and electrical stimulation, potentially improving treatment efficacy and patient compliance. Retinal prostheses and optogenetics provide hope for restoring vision in patients with degenerative retinal diseases. However, the review emphasizes that many of these technologies are still in the research and development phase. Key challenges that must be overcome for clinical translation include improving sensor accuracy and reliability, ensuring stable wireless power and data transmission, addressing issues of comfort and biocompatibility for long-term wear, and conducting rigorous clinical trials to validate the correlation between tear biomarkers and disease states. The integration of artificial intelligence and multifunctional capabilities into SCLs is seen as a crucial future direction for creating closed-loop, personalized healthcare platforms.