Transforming Vision: Hyaluronic Acid in Ophthalmology

Known for its biocompatibility, viscoelasticity, and exceptional water-retaining capabilities, HA plays a pivotal role across numerous therapeutic areas. Notably, ophthalmology was the first field to harness the power of HA, setting the stage for decades of innovation in ocular treatments.

An Indispensable biopolymer in Ophthalmology

Found naturally in the eye and connective tissues, HA contributes to lubrication, maintaining tissue hydration, and cellular repair — features that are particularly beneficial in the delicate environment of ocular structures. Since its first FDA approval in 1979 with Healon, HA has become foundational in a wide array of ophthalmic procedures and therapies.

Established Applications of HA in Ophthalmology

• Cataract Surgery 

One of HA’s earliest and most established uses is in cataract surgery. HA-based viscoelastics are used to maintain the anterior chamber, protect the corneal endothelium, and support intraocular lens (IOL) implantation. These formulations reduce mechanical trauma and ensure a smoother surgical process. 2 

• Corneal Transplantation 

In corneal transplants, HA helps preserve donor corneas by maintaining hydration and structural integrity. This contributes to better tissue viability and postoperative healing, supporting the graft’s integration into the host eye. 2 

• Glaucoma Surgery 

During procedures such as goniotomy or trabeculectomy, HA maintains space within the eye, helping to prevent tissue collapse and aid surgical precision. It also contributes to improved postoperative recovery by reducing inflammation and supporting wound healing. 2 

• Dry Eye Disease 

HA-based eye drops are a frontline treatment for dry eye syndrome. By enhancing tear film stability and hydrating the ocular surface, HA alleviates symptoms such as irritation, burning, and visual fatigue. Its ability to retain moisture makes it particularly effective for long-term management. 3, 4, 5

Advancing Innovation: Next-Generation Uses of HA

As research advances, HA continues to be at the center of innovative solutions in eye care. 

• Intravitreal Drug Delivery 

HA is being studied as a carrier for intravitreal injections, particularly for retinal conditions like age-related macular degeneration (AMD) and diabetic retinopathy. By controlling drug release and extending therapeutic duration, HA-based systems could reduce injection frequency and improve patient outcomes. 6, 7, 8

• Corneal Regeneration 

HA-infused contact lenses and hydrogel formulations are being developed to accelerate healing after corneal injury or surgery. These materials deliver moisture and create a protective barrier that promotes epithelial regeneration. 9, 10

• Smart Drug Delivery Systems 

Cutting-edge delivery technologies are incorporating HA into mucoadhesive inserts, hydrogels, and nanoparticles. 7, 8 One example is a preclinical ophthalmic insert that transforms into a hydrogel pellet on the eye’s surface, delivering drugs steadily over several days—potentially transforming treatment adherence. 11 

• Anti-Scarring Applications 

Postoperative scarring remains a risk in many ophthalmic procedures. HA’s anti-fibrotic potential is being explored to prevent excessive tissue formation, particularly after glaucoma surgeries. Reducing scarring could preserve surgical success and long-term vision outcomes. 3, 10, 12 

The Future of HA in Ophthamology

Cutting-edge research is now focusing on customizing HA molecules to enhance therapeutic properties. Scientists are also investigating its integration with stem cell therapies for retinal regeneration, aiming to create supportive scaffolds that promote cellular differentiation and repair in degenerative eye diseases. 

Additionally, HA is being explored for use as an artificial vitreous substitute—a potential game-changer for patients undergoing vitrectomy for retinal conditions. 

From its foundational role in cataract surgery to its promise in next-generation regenerative medicine, hyaluronic acid continues to redefine what’s possible in ophthalmology. Its unique combination of hydration, lubrication, and biocompatibility makes it an essential molecule in both established procedures and pioneering research. 

References 

1. Scholtz S. History of Ophthalmic Viscosurgical Devices[Internet]. 2007. CRST GLOBAL. Available from: https://crstodayeurope.com/articles/2007- jan/0107_06-php/. 
2. Higashide T, Sugiyama K. Use of viscoelastic substance in ophthalmic surgery – focus on sodium hyaluronate. Clin Ophthalmol. 2008;2(1):21–30. doi:10.2147/opth.s1439. 
3. Fallacara A, Baldini E, Manfredini S, Vertuani S. Hyaluronic Acid in the Third Millennium. Polymers. 2018;10:701. doi:10.3390/polym10070701 
4. Vasvani S, Kulkarni P, Rawtani D. Hyaluronic acid: A review on its biology, aspects of drug delivery, route of administrations and a special emphasis on its approved marketed products and recent clinical studies. Int J Biol Macromol. 2020;151:1012-1029. doi:10.1016/j.ijbiomac.2019.11.066. 
5. Caruso C, D’Andrea L, Rinaldi M, Senese I, Piscopo R, Costagliola C. Modified Sodium hyaluronate conjugated to riboflavin (Har® 0.1%) as lubricant eyedrops in the treatment of dry eye: A prospective randomised study. Heliyon. 2024; 10(15): e35527. doi: 10.1016/j.heliyon.2024.e35527. 
6. Rafael D, Guerrero M, Marican A, Arango D, Sarmento B, Ferrer R, Durán-Lara EF, Clark SJ, Schwartz S Jr. Delivery Systems in Ocular Retinopathies: The Promising Future of Intravitreal Hydrogels as Sustained Release Scaffolds. Pharmaceutics. 2023;15(5):1484. doi:10.3390/ pharmaceutics15051484. 
7. Jiménez-Gómez Y, Alba-Molina D, Blanco-Blanco M, Pérez-Fajardo L, Reyes-Ortega F, Ortega-Llamas L, Villalba-González M, Fernández-Choquet de Isla I, Pugliese F, Stoikow I, González-Andrades M. Novel Treatments for Age-Related Macular Degeneration: A Review of Clinical Advances in Sustained Drug Delivery Systems.Pharmaceutics.2022;14(7):1473.doi:10.3390/pharmaceutics14071473 
8. Batur E, Özdemir S, Durgun ME, özsoy Y. Vesicular Drug Delivery Systems: Promising Approaches in Ocular Drug Delivery. Pharmaceuticals. 2024;17:511 doi:10.3390/ph17040511. 
9. Dong Q, Wu D, Li M, Dong W. Polysaccharides, as biological macromolecule-based scaffolding biomaterials in cornea tissue engineering: A review. Tissue Cell. 2022;76:101782. doi:10.1016/j.tice.2022.101782 
10. Bucolo C, Maugeri G, Giunta S, D’Agata V, Drago F, Romano GL. Corneal wound healing and nerve regeneration by novel ophthalmic formulations based on cross-linked sodium hyaluronate, taurine, vitamin B6, and vitamin B12. Front Pharmacol. 2023;14:1109291. doi:10.3389/fphar.2023.1109291. 
11. Biophta. Biophta’s mini-table [Internet]. Biophta. Available from: https://www.biophta.com/technology/#Insert (accessed 31 July 2024). 
12. Wang X, Dai WW, Dang YL, Hong Y, Zhang C. Five Years’ Outcomes of Trabeculectomy with Cross-linked Sodium Hyaluronate Gel Implantation for Chinese Glaucoma Patients. Chin Med J (Engl). 2018;131(13):1562–8. doi:10.4103/0366-6999.233655.