Medical Uses of Hyaluronic Acid
Hyaluronic acid has established medical applications in ophthalmology for eye surgery and dry eye disease, in rheumatology for knee osteoarthritis (though with significant controversy and conditional recommendations against routine use), in dermatology for wound healing and skin rejuvenation, and in aesthetic medicine for lip augmentation and facial volumization. 1, 2, 3
Ophthalmological Applications
Hyaluronic acid is strongly established as a viscoelastic surgical aid in cataract surgery, where it facilitates procedures and protects the corneal endothelium through its lubricating and cushioning properties. 2 The role extends to other eye surgeries including penetrating keratoplasty, trabeculectomy, retinal reattachment, and trauma surgery, though efficacy in these indications is less well-defined. 2
For dry eye disease, hyaluronic acid provides water retention and lubricant properties that challenge current standard treatments through its exceptional hydration capacity. 3
Rheumatological Applications - Knee Osteoarthritis
Current Guideline Stance
The 2020 American College of Rheumatology/Arthritis Foundation conditionally recommends AGAINST intra-articular hyaluronic acid injections for knee osteoarthritis, based on meta-analyses showing that when limited to low-risk-of-bias trials, the effect size compared to saline injections approaches zero. 1 The 2022 American Academy of Orthopaedic Surgeons similarly recommends against routine use, though acknowledging a calculated number needed to treat of 17 patients. 1
When It May Still Be Considered
Despite the conditional recommendation against, hyaluronic acid may be used in shared decision-making when other alternatives have been exhausted or failed, including non-pharmacologic therapies, topical and oral NSAIDs, and intra-articular corticosteroids. 1, 4, 5 The conditional (not strong) recommendation acknowledges that some subset of patients may benefit, though current evidence cannot identify which patients. 1
Historical Evidence Context
Older EULAR guidelines (2003) showed evidence supporting hyaluronic acid for pain reduction (effect sizes 0.04-0.9) and functional improvement (effect size 0.36) over periods of 60 days to one year. 1 However, these benefits were offset by slower onset of action compared to corticosteroids and the requirement of 3-5 weekly injections. 1
Patients over 60 years with important functional impairment responded better to hyaluronic acid, while those with severe disease or baseline effusion had worse outcomes. 1 Most trials excluded severe osteoarthritis. 1
Hip and Hand Osteoarthritis
Hyaluronic acid is strongly recommended AGAINST for hip osteoarthritis due to higher quality evidence showing lack of benefit. 1 For first carpometacarpal joint osteoarthritis, it is conditionally recommended against. 1
Dermatological and Wound Healing Applications
Radiation-Related Vaginal Toxicity
Topical hyaluronic acid combined with vitamins E and A prevents acute and late vaginal toxicities in gynecological cancer patients receiving radiotherapy, reducing dyspareunia, vaginal mucosal inflammation, dryness, bleeding, fibrosis, and cellular atypia through support of the extracellular matrix and keratinocyte proliferation. 1
General Dermatological Uses
Hyaluronic acid improves tissue hydration, elasticity, and cellular resistance to mechanical damage in aesthetic dermatology. 6 It provides moisturizing and dermal filling effects with marginal adverse effects. 6 The concentration in tissues decreases with age, contributing to loss of tissue function and structure. 7
Aesthetic Medicine Applications
Lip Augmentation
Hyaluronic acid fillers are the primary option for lip augmentation, creating harmonious volumizing with lasting 3D effects for 6-18 months. 8 Administration should use 27-30 gauge needles or 22-25 gauge cannula, injecting 0.2-0.5 mL per quadrant in a retrograde fashion above the orbicularis oris muscle to avoid vascular complications. 8
Periorbital Rejuvenation
For the delicate periorbital region, hyaluronic acid demonstrates satisfactory outcomes in improving pigmentation and skin condition, though small gauge needles (30G) and careful technique are essential due to proximity to the eye. 1
Pharmacological Properties and Safety
Hyaluronic acid is a naturally occurring polysaccharide and major component of the extracellular matrix of connective tissues. 9 Do not use concomitantly with disinfectants containing quaternary ammonium salts, as hyaluronic acid can precipitate in their presence. 9 Concomitant topical treatment with antibiotics or other local agents has not caused interactions or incompatibilities. 9
The molecule exhibits strong hydration and viscoelasticity properties that depend on molecular weight, with high molecular weight preparations potentially offering superior effects in some applications. 1, 7, 10
Common Pitfalls to Avoid
- Do not use hyaluronic acid injections as first-line treatment for knee osteoarthritis—exhaust non-pharmacologic therapies, NSAIDs, and corticosteroid injections first. 1, 4, 5
- Avoid assuming all hyaluronic acid formulations are equivalent—molecular weight and preparation methods significantly affect clinical outcomes. 1
- Do not inject superficially in aesthetic applications—maintain depth above the orbicularis oris muscle in lips to prevent vascular injury. 8
- Avoid using hyaluronic acid in patients with severe osteoarthritis or baseline joint effusion—these patients demonstrate worse outcomes. 1
- Do not expect rapid onset of action—hyaluronic acid has slower onset compared to corticosteroids, though potentially longer duration. 1