Hyaluronic acid fillers have become a cornerstone of modern aesthetic medicine, offering predictable and reversible volume restoration for facial aging concerns. However, the reversibility of these products depends entirely on understanding the biochemistry of hyaluronic acid degradation and the proper use of hyaluronidase enzyme. When complications arise from filler placement—particularly in the delicate periocular region—the ability to safely and effectively dissolve the product requires both clinical expertise and a foundation in the current evidence base.

At The Pur Health, Dr. Munib's approach to filler dissolution is grounded in peer-reviewed research and an understanding of the molecular properties that influence treatment outcomes. The decision to dissolve and reset filler is not simply a technical procedure but a medical intervention that requires careful assessment, appropriate dosing, and individualized treatment planning.

Hyaluronic acid fillers have become a cornerstone of modern aesthetic medicine, offering predictable and reversible volume restoration for facial aging concerns. However, the reversibility of these products depends entirely on understanding the biochemistry of hyaluronic acid degradation and the proper use of hyaluronidase enzyme. When complications arise from filler placement—particularly in the delicate periocular region—the ability to safely and effectively dissolve the product requires both clinical expertise and a foundation in the current evidence base.

At The Pur Health, Dr. Munib's approach to filler dissolution is grounded in peer-reviewed research and an understanding of the molecular properties that influence treatment outcomes. The decision to dissolve and reset filler is not simply a technical procedure but a medical intervention that requires careful assessment, appropriate dosing, and individualized treatment planning.

Understanding Hyaluronidase and Its Mechanism of Action

Hyaluronidase is an enzyme that catalyzes the hydrolytic cleavage of hyaluronic acid, breaking down the glycosidic bonds that hold the polymer chains together. When injected into tissue containing hyaluronic acid filler, the enzyme disperses through the treatment area and begins degrading the filler material, converting it into smaller molecular weight fragments that the body can metabolize and eliminate.

The effectiveness of hyaluronidase depends on several factors, including the type and concentration of enzyme used, the degree of cross-linking in the target filler, and the volume and location of the product being dissolved. Both ovine-derived and recombinant human hyaluronidase formulations are clinically effective, though their potency and dispersion characteristics differ slightly. Recent comparative studies have demonstrated that both formulations successfully degrade hyaluronic acid fillers when used at appropriate concentrations, though recombinant human hyaluronidase may offer advantages in patients with concerns about animal-derived products or prior sensitization.

The enzymatic activity of hyaluronidase is concentration-dependent, and proper dilution is essential for achieving adequate dispersion throughout the treatment area. Research supports a minimum dilution ratio of three parts enzyme to one part diluent to ensure sufficient enzymatic activity while allowing for controlled diffusion. Overdilution reduces the concentration of active enzyme per injection site, potentially requiring additional treatments, while inadequate dilution may result in uneven degradation or localized tissue reactions.

Understanding Hyaluronidase and Its Mechanism of Action

Hyaluronidase is an enzyme that catalyzes the hydrolytic cleavage of hyaluronic acid, breaking down the glycosidic bonds that hold the polymer chains together. When injected into tissue containing hyaluronic acid filler, the enzyme disperses through the treatment area and begins degrading the filler material, converting it into smaller molecular weight fragments that the body can metabolize and eliminate.

The effectiveness of hyaluronidase depends on several factors, including the type and concentration of enzyme used, the degree of cross-linking in the target filler, and the volume and location of the product being dissolved. Both ovine-derived and recombinant human hyaluronidase formulations are clinically effective, though their potency and dispersion characteristics differ slightly. Recent comparative studies have demonstrated that both formulations successfully degrade hyaluronic acid fillers when used at appropriate concentrations, though recombinant human hyaluronidase may offer advantages in patients with concerns about animal-derived products or prior sensitization.

The enzymatic activity of hyaluronidase is concentration-dependent, and proper dilution is essential for achieving adequate dispersion throughout the treatment area. Research supports a minimum dilution ratio of three parts enzyme to one part diluent to ensure sufficient enzymatic activity while allowing for controlled diffusion. Overdilution reduces the concentration of active enzyme per injection site, potentially requiring additional treatments, while inadequate dilution may result in uneven degradation or localized tissue reactions.

Why Filler Type Matters: The Role of Cross-Linking and Rheology

Not all hyaluronic acid fillers respond identically to hyaluronidase, and understanding the rheological properties of different products is critical for predicting treatment response. Fillers are manufactured with varying degrees of cross-linking, which refers to the chemical bonds that connect hyaluronic acid chains to one another. Higher cross-linking creates a more cohesive, longer-lasting gel that resists enzymatic degradation, while lower cross-linking results in a softer product that dissolves more readily.

Clinical studies evaluating the response of different filler brands to hyaluronidase have shown significant variation in dissolution rates. Fillers such as Juvéderm Ultra XC and products in the RHA series, which have higher degrees of cross-linking, require higher doses of hyaluronidase or repeated treatments to achieve complete dissolution. In contrast, fillers like Restylane-L, which are less extensively cross-linked, degrade more readily with lower enzyme doses. This variability underscores the importance of knowing which filler product was originally injected before attempting dissolution, as a one-size-fits-all dosing approach may result in incomplete correction or unnecessary exposure to additional enzyme.

The molecular structure of the filler also influences how the enzyme disperses through the tissue. More cohesive gels may limit the spread of hyaluronidase, requiring multiple injection points or higher concentrations to ensure thorough degradation. Understanding these product-specific characteristics allows for more precise treatment planning and reduces the likelihood of residual filler remaining after dissolution attempts.

Why Filler Type Matters: The Role of Cross-Linking and Rheology

Not all hyaluronic acid fillers respond identically to hyaluronidase, and understanding the rheological properties of different products is critical for predicting treatment response. Fillers are manufactured with varying degrees of cross-linking, which refers to the chemical bonds that connect hyaluronic acid chains to one another. Higher cross-linking creates a more cohesive, longer-lasting gel that resists enzymatic degradation, while lower cross-linking results in a softer product that dissolves more readily.

Clinical studies evaluating the response of different filler brands to hyaluronidase have shown significant variation in dissolution rates. Fillers such as Juvéderm Ultra XC and products in the RHA series, which have higher degrees of cross-linking, require higher doses of hyaluronidase or repeated treatments to achieve complete dissolution. In contrast, fillers like Restylane-L, which are less extensively cross-linked, degrade more readily with lower enzyme doses. This variability underscores the importance of knowing which filler product was originally injected before attempting dissolution, as a one-size-fits-all dosing approach may result in incomplete correction or unnecessary exposure to additional enzyme.

The molecular structure of the filler also influences how the enzyme disperses through the tissue. More cohesive gels may limit the spread of hyaluronidase, requiring multiple injection points or higher concentrations to ensure thorough degradation. Understanding these product-specific characteristics allows for more precise treatment planning and reduces the likelihood of residual filler remaining after dissolution attempts.

The Case for Low-Dose, Multidose Hyaluronidase Protocols

Traditional approaches to filler dissolution often involved administering large doses of hyaluronidase in a single session, with the goal of achieving rapid and complete degradation. However, emerging evidence supports the use of low-dose, multidose protocols, particularly in anatomically sensitive areas such as the periocular region. This approach allows for gradual sculpting of the treatment area, minimizing the risk of overcorrection and providing better control over the final aesthetic outcome. This is where Dr. Munib excels using Ultrasound to dissolve filler. Her results speak for themselves.

A randomized clinical trial published in JAMA Dermatology evaluated the effectiveness of low-dose hyaluronidase for removing hyaluronic acid filler nodules and found that incremental dosing achieved successful dissolution while reducing adverse effects. The study demonstrated that lower doses administered in multiple sessions allowed clinicians to titrate the enzyme based on clinical response, stopping once the desired correction was achieved rather than risking excessive tissue degradation.

This titration-based approach is especially valuable in the under-eye area, where the skin is thin, the underlying anatomy is complex, and even minor overcorrection can result in visible hollowing or asymmetry. By administering small doses and reassessing at weekly intervals, clinicians can achieve precise correction without the complications associated with aggressive single-dose treatments. The ability to repeat injections as needed, rather than committing to a high initial dose, provides a margin of safety that is particularly important when working near the orbital structures.

The Case for Low-Dose, Multidose Hyaluronidase Protocols

Traditional approaches to filler dissolution often involved administering large doses of hyaluronidase in a single session, with the goal of achieving rapid and complete degradation. However, emerging evidence supports the use of low-dose, multidose protocols, particularly in anatomically sensitive areas such as the periocular region. This approach allows for gradual sculpting of the treatment area, minimizing the risk of overcorrection and providing better control over the final aesthetic outcome. This is where Dr. Munib excels using Ultrasound to dissolve filler. Her results speak for themselves.

A randomized clinical trial published in JAMA Dermatology evaluated the effectiveness of low-dose hyaluronidase for removing hyaluronic acid filler nodules and found that incremental dosing achieved successful dissolution while reducing adverse effects. The study demonstrated that lower doses administered in multiple sessions allowed clinicians to titrate the enzyme based on clinical response, stopping once the desired correction was achieved rather than risking excessive tissue degradation.

This titration-based approach is especially valuable in the under-eye area, where the skin is thin, the underlying anatomy is complex, and even minor overcorrection can result in visible hollowing or asymmetry. By administering small doses and reassessing at weekly intervals, clinicians can achieve precise correction without the complications associated with aggressive single-dose treatments. The ability to repeat injections as needed, rather than committing to a high initial dose, provides a margin of safety that is particularly important when working near the orbital structures.

Individualized Dosing: Why There Is No Universal Protocol

Despite the widespread use of hyaluronidase in clinical practice, there is currently no universally standardized dosing protocol for filler dissolution. The optimal dose varies based on multiple factors, including the type of filler, the volume of product present, the anatomic location, and the time elapsed since the original injection. Older filler that has been present for months or years may be partially degraded by the body's natural enzymatic processes, requiring less hyaluronidase for complete removal, while recently injected filler may be more resistant.

Dr. Munib's approach at The Pur Health involves careful clinical assessment before initiating hyaluronidase treatment. This includes reviewing the patient's injection history when available, examining the distribution and characteristics of the existing filler, and considering any signs of inflammation or vascular compromise. Based on this assessment, an individualized dosing plan is developed, with the understanding that additional sessions may be necessary depending on the response to initial treatment.

Research continues to refine best practices for hyaluronidase use, with ongoing studies examining the time- and dose-dependent effects of the enzyme on different filler formulations. In vitro studies have demonstrated that degradation occurs in a predictable pattern based on enzyme concentration and contact time, but translating these findings to clinical practice requires accounting for the complexity of living tissue, including factors such as blood flow, lymphatic drainage, and inflammatory responses that influence durg distribution and activity.

Individualized Dosing: Why There Is No Universal Protocol

Despite the widespread use of hyaluronidase in clinical practice, there is currently no universally standardized dosing protocol for filler dissolution. The optimal dose varies based on multiple factors, including the type of filler, the volume of product present, the anatomic location, and the time elapsed since the original injection. Older filler that has been present for months or years may be partially degraded by the body's natural enzymatic processes, requiring less hyaluronidase for complete removal, while recently injected filler may be more resistant.

Dr. Munib's approach at The Pur Health involves careful clinical assessment before initiating hyaluronidase treatment. This includes reviewing the patient's injection history when available, examining the distribution and characteristics of the existing filler, and considering any signs of inflammation or vascular compromise. Based on this assessment, an individualized dosing plan is developed, with the understanding that additional sessions may be necessary depending on the response to initial treatment.

Research continues to refine best practices for hyaluronidase use, with ongoing studies examining the time- and dose-dependent effects of the enzyme on different filler formulations. In vitro studies have demonstrated that degradation occurs in a predictable pattern based on enzyme concentration and contact time, but translating these findings to clinical practice requires accounting for the complexity of living tissue, including factors such as blood flow, lymphatic drainage, and inflammatory responses that influence durg distribution and activity.

Managing Periocular Filler Complications: When Dissolution Is Necessary

The periocular region presents unique challenges for filler placement due to the delicate nature of the tissues and the proximity to critical structures such as the orbital vessels and the globe itself. Complications from under-eye filler can range from aesthetic concerns such as the Tyndall effect—a bluish discoloration caused by superficially placed filler—to more serious issues including persistent edema, filler migration, and in rare cases, vascular compromise.

The Tyndall effect occurs when hyaluronic acid filler is placed too superficially in the skin, causing light to scatter and creating a visible bluish or grayish tinge. This is particularly problematic in the thin skin of the lower eyelid, where even small amounts of superficial product can be cosmetically bothersome. Dissolution with hyaluronidase effectively resolves this issue by removing the offending filler, allowing the skin color to return to baseline.

Filler migration is another common indication for dissolution. Over time, hyaluronic acid can shift from its original injection site due to muscle movement, gravitational forces, or improper placement technique. In the under-eye area, this can result in puffiness, irregular contours, or a "sausage-like" appearance along the lower lid margin. Attempting to correct migration by adding more filler often exacerbates the problem, making dissolution and reset the preferred approach.

Persistent edema—swelling that does not resolve weeks or months after injection—can be caused by several factors, including inflammatory reactions to the filler, lymphatic obstruction, or the hygroscopic properties of hyaluronic acid drawing excess fluid into the tissue. When conservative measures such as massage, warm compresses, or anti-inflammatory medications fail to resolve the swelling, hyaluronidase dissolution provides definitive treatment.

Managing Periocular Filler Complications: When Dissolution Is Necessary

The periocular region presents unique challenges for filler placement due to the delicate nature of the tissues and the proximity to critical structures such as the orbital vessels and the globe itself. Complications from under-eye filler can range from aesthetic concerns such as the Tyndall effect—a bluish discoloration caused by superficially placed filler—to more serious issues including persistent edema, filler migration, and in rare cases, vascular compromise.

The Tyndall effect occurs when hyaluronic acid filler is placed too superficially in the skin, causing light to scatter and creating a visible bluish or grayish tinge. This is particularly problematic in the thin skin of the lower eyelid, where even small amounts of superficial product can be cosmetically bothersome. Dissolution with hyaluronidase effectively resolves this issue by removing the offending filler, allowing the skin color to return to baseline.

Filler migration is another common indication for dissolution. Over time, hyaluronic acid can shift from its original injection site due to muscle movement, gravitational forces, or improper placement technique. In the under-eye area, this can result in puffiness, irregular contours, or a "sausage-like" appearance along the lower lid margin. Attempting to correct migration by adding more filler often exacerbates the problem, making dissolution and reset the preferred approach.

Persistent edema—swelling that does not resolve weeks or months after injection—can be caused by several factors, including inflammatory reactions to the filler, lymphatic obstruction, or the hygroscopic properties of hyaluronic acid drawing excess fluid into the tissue. When conservative measures such as massage, warm compresses, or anti-inflammatory medications fail to resolve the swelling, hyaluronidase dissolution provides definitive treatment.

The Importance of the Waiting Period Between Dissolution and Reset

After hyaluronidase treatment, a waiting period of three to four weeks is recommended before re-injecting filler. This interval allows for complete resolution of any residual enzyme activity, elimination of degraded filler fragments, and normalization of tissue inflammation. Rushing to re-treat before the tissue has fully recovered can lead to unpredictable results, as residual swelling or enzymatic activity may distort the anatomy and make it difficult to assess the true volume deficit.

During this waiting period, the under-eye area returns to its baseline appearance, which may include the original hollowing, shadowing, or volume loss that prompted the initial filler treatment. While some patients find this temporary regression aesthetically concerning, it is a necessary step in the correction process. By allowing the tissue to stabilize completely, Dr. Munib can accurately assess the degree of volume restoration needed and place the new filler with precision.

The reset phase involves careful selection of filler type, appropriate volume calculation, and strategic injection technique to avoid repeating the complications that necessitated dissolution. At The Pur Health, this process is guided by a thorough understanding of facial anatomy, the biomechanical properties of different filler products, and the patient's aesthetic goals. The objective is not simply to replace the dissolved filler but to achieve a natural, harmonious result that enhances the periocular region without creating new problems.

The Importance of the Waiting Period Between Dissolution and Reset

After hyaluronidase treatment, a waiting period of three to four weeks is recommended before re-injecting filler. This interval allows for complete resolution of any residual enzyme activity, elimination of degraded filler fragments, and normalization of tissue inflammation. Rushing to re-treat before the tissue has fully recovered can lead to unpredictable results, as residual swelling or enzymatic activity may distort the anatomy and make it difficult to assess the true volume deficit.

During this waiting period, the under-eye area returns to its baseline appearance, which may include the original hollowing, shadowing, or volume loss that prompted the initial filler treatment. While some patients find this temporary regression aesthetically concerning, it is a necessary step in the correction process. By allowing the tissue to stabilize completely, Dr. Munib can accurately assess the degree of volume restoration needed and place the new filler with precision.

The reset phase involves careful selection of filler type, appropriate volume calculation, and strategic injection technique to avoid repeating the complications that necessitated dissolution. At The Pur Health, this process is guided by a thorough understanding of facial anatomy, the biomechanical properties of different filler products, and the patient's aesthetic goals. The objective is not simply to replace the dissolved filler but to achieve a natural, harmonious result that enhances the periocular region without creating new problems.

Evidence-Based Practice in Aesthetic Medicine

The use of hyaluronidase for filler dissolution exemplifies the importance of evidence-based practice in aesthetic medicine. While the procedure is common in clinical settings, optimal outcomes depend on understanding the underlying science, staying current with evolving research, and applying clinical judgment to individualize treatment. Dr. Munib's approach at The Pur Health integrates the latest peer-reviewed evidence with years of clinical experience, ensuring that patients receive care that is both medically sound and tailored to their specific needs.

As research continues to advance our understanding of hyaluronic acid degradation, filler rheology, and enzymatic activity, treatment protocols will continue to evolve. The commitment to ongoing education and evidence-based practice ensures that patients benefit from the most current and effective approaches available, minimizing complications and optimizing aesthetic outcomes.

For patients dealing with under-eye filler complications, consultation with a physician who understands both the art and science of filler dissolution is essential. At The Pur Health, Dr. Munib provides comprehensive evaluation, evidence-based treatment planning, and meticulous execution to help patients achieve safe and satisfying correction of filler-related concerns.

Evidence-Based Practice in Aesthetic Medicine

The use of hyaluronidase for filler dissolution exemplifies the importance of evidence-based practice in aesthetic medicine. While the procedure is common in clinical settings, optimal outcomes depend on understanding the underlying science, staying current with evolving research, and applying clinical judgment to individualize treatment. Dr. Munib's approach at The Pur Health integrates the latest peer-reviewed evidence with years of clinical experience, ensuring that patients receive care that is both medically sound and tailored to their specific needs.

As research continues to advance our understanding of hyaluronic acid degradation, filler rheology, and enzymatic activity, treatment protocols will continue to evolve. The commitment to ongoing education and evidence-based practice ensures that patients benefit from the most current and effective approaches available, minimizing complications and optimizing aesthetic outcomes.

For patients dealing with under-eye filler complications, consultation with a physician who understands both the art and science of filler dissolution is essential. At The Pur Health, Dr. Munib provides comprehensive evaluation, evidence-based treatment planning, and meticulous execution to help patients achieve safe and satisfying correction of filler-related concerns.

References

FDA Orange Book. FDA Orange Book.Alam M, Hughart R, Geisler A, et al. Effectiveness of Low Doses of Hyaluronidase to Remove Hyaluronic Acid Filler Nodules: A Randomized Clinical Trial. JAMA Dermatology. 2018;154(7):765-772. doi:10.1001/jamadermatol.2018.0515.
Zoumalan CI. Managing Periocular Filler-Related Syndrome Prior to Lower Blepharoplasty. Aesthetic Plastic Surgery. 2019;43(1):115-122. doi:10.1007/s00266-018-1250-7.
Mandal P, Gama F. The Use of Periocular Fillers in Aesthetic Medicine. Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS. 2021;74(7):1602-1609. doi:10.1016/j.bjps.2020.12.079.
Ryu C, Lu JE, Zhang-Nunes S. Response of Twelve Different Hyaluronic Acid Gels to Varying Doses of Recombinant Human Hyaluronidase. Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS. 2021;74(4):881-889. doi:10.1016/j.bjps.2020.10.051.
Safran T, Khalaf R, Metelitsa A, Woodward J, Nikolis A. Comparison of the Degradability of Hyaluronic Acid by Ovine and Recombinant Human Hyaluronidase. Aesthetic Surgery Journal. 2025;:sjaf127. doi:10.1093/asj/sjaf127.
Sudharshan R, Davuluru SS, Shen AJ, et al. Identifying Minimum Single Dose of Recombinant Human Hyaluronidase for in Vitro Dissolution of Twenty-Two Hyaluronic Acid Fillers. Ophthalmic Plastic and Reconstructive Surgery. 2025;:00002341-990000000-00600. doi:10.1097/IOP.0000000000002941.
Flégeau K, Jing J, Brusini R, et al. Multidose Hyaluronidase Administration as an Optimal Procedure to Degrade Resilient Hyaluronic Acid Soft Tissue Fillers. Molecules (Basel, Switzerland). 2023;28(3):1003. doi:10.3390/molecules28031003.
Gerber PA, Buhren BA, Bölke E, et al. Time- And Dose-Dependent Effects of Hyaluronidase on the Degradation of Different Hyaluronan-Based Fillers in Vitro. Plastic and Reconstructive Surgery. 2023;151(3):560-567. doi:10.1097/PRS.0000000000009916.

References

FDA Orange Book. FDA Orange Book.Alam M, Hughart R, Geisler A, et al. Effectiveness of Low Doses of Hyaluronidase to Remove Hyaluronic Acid Filler Nodules: A Randomized Clinical Trial. JAMA Dermatology. 2018;154(7):765-772. doi:10.1001/jamadermatol.2018.0515.
Zoumalan CI. Managing Periocular Filler-Related Syndrome Prior to Lower Blepharoplasty. Aesthetic Plastic Surgery. 2019;43(1):115-122. doi:10.1007/s00266-018-1250-7.
Mandal P, Gama F. The Use of Periocular Fillers in Aesthetic Medicine. Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS. 2021;74(7):1602-1609. doi:10.1016/j.bjps.2020.12.079.
Ryu C, Lu JE, Zhang-Nunes S. Response of Twelve Different Hyaluronic Acid Gels to Varying Doses of Recombinant Human Hyaluronidase. Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS. 2021;74(4):881-889. doi:10.1016/j.bjps.2020.10.051.
Safran T, Khalaf R, Metelitsa A, Woodward J, Nikolis A. Comparison of the Degradability of Hyaluronic Acid by Ovine and Recombinant Human Hyaluronidase. Aesthetic Surgery Journal. 2025;:sjaf127. doi:10.1093/asj/sjaf127.
Sudharshan R, Davuluru SS, Shen AJ, et al. Identifying Minimum Single Dose of Recombinant Human Hyaluronidase for in Vitro Dissolution of Twenty-Two Hyaluronic Acid Fillers. Ophthalmic Plastic and Reconstructive Surgery. 2025;:00002341-990000000-00600. doi:10.1097/IOP.0000000000002941.
Flégeau K, Jing J, Brusini R, et al. Multidose Hyaluronidase Administration as an Optimal Procedure to Degrade Resilient Hyaluronic Acid Soft Tissue Fillers. Molecules (Basel, Switzerland). 2023;28(3):1003. doi:10.3390/molecules28031003.
Gerber PA, Buhren BA, Bölke E, et al. Time- And Dose-Dependent Effects of Hyaluronidase on the Degradation of Different Hyaluronan-Based Fillers in Vitro. Plastic and Reconstructive Surgery. 2023;151(3):560-567. doi:10.1097/PRS.0000000000009916.