Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 17:18:1741-1752.
doi: 10.2147/CCID.S518475. eCollection 2025.

Hyaluronic Acid Combined with Diluted and Hyperdiluted Calcium Hydroxylapatite to Treat the Periocular Area

Julieta Spada  1 , Jani Van Loghem  2
Affiliations

Hyaluronic Acid Combined with Diluted and Hyperdiluted Calcium Hydroxylapatite to Treat the Periocular Area

Julieta Spada et al. Clin Cosmet Investig Dermatol. .

Abstract

Purpose: A combination of fillers and other modalities is often required to address all signs of periorbital aging. Patients are injected for volume loss, and for hyperpigmentation are treated with a combination treatments with chemical peels and lasers, but multiple visits can be burdensome. To streamline the current treatment approach for the periocular area, the current study investigated the benefit of the treatment with a blend of Hyaluronic Acid (HA) and Calcium Hydroxylapatite (CaHA). This dual-filler strategy is designed to utilize the rheological and volume replacement capabilities of HA alongside the bioregenerative effects of CaHA while avoiding excessive edema and/or delayed swelling that may occur when HA is injected alone.

Methods: One hundred and six adults were treated with a blend of crosslinked HA (22.5 mg/mL) and diluted/hyperdiluted CaHA. The filler ratio was chosen based on individual skin thickness and depth of palpebro-malar groove (PG) or supraorbital hollowness (SH). Assessments were performed at baseline (T0), 30, 60, 90, and 365 days. One patient underwent a comparative analysis of HA alone versus the HA-CaHA blend, evaluated through ultrasound, Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) scan post-injection.

Results: All treated patients presented natural-looking results, less pronounced PG and SH with minimal edema on D30, and skin quality improvement with less laxity, wrinkling and pigmentation. No hyaluronidase injections for overcorrections were required. No severe complications were observed. For most patients, results varied according to the dilution of the blend; lower dilutions (1:1) lasted longer than higher dilution (1:4), even though results were still noticeable for patients treated with the latter (1:4) at the 1-year evaluation.

Conclusion: This study validates the use of a HA and CaHA blend (CaHA-CPM) for periocular rejuvenation, addressing various aging symptoms in this complex facial region.

Keywords: A-frame deformity; calcium hydroxylapatite; hyaluronic acid filler injection; periocular; sunken upper eyelids; superior sulcus syndrome; supraorbital hollowness; tear trough.

PubMed Disclaimer

Conflict of interest statement

Dr Spada and Dr Van Loghem are global speakers for Merz Aesthetics. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
GAIS score at 30-day evaluation.
Figure 2
Figure 2
GAIS score at 60-day or more evaluation. Improvement.
Figure 3
Figure 3
Modified Sadick Scale scores at baseline, 30 and 60 days.
Figure 4
Figure 4
46 yo. Female received treatment for the palpebromalar groove with CaHA-CPMB blend (with CaHA with 1:4 dilution). (A) Before. (B) 30 days after 1st injection. (C) 60 days after 1st injection. (D) 1yr after injection. (E) 60 days after 2nd injection CaHA-CPMB (CaHa with 1:1 dilution). (F) 5 months after 2nd injection.
Figure 5
Figure 5
38 yo. Female received treatment for the sunken upper eyelids and palpebromalar groove with CaHA-CPMB blend (CaHA with 1:4 dilution). (A) Before. (B) 30 days after 1st injection. (C) 60 days after 1st injection. (D) 8 months after injection. (E) 30 days after 2nd injection CaHA-CPMB blend (CaHA with 1:1 dilution). (F) 1yr and 7 months after 2nd injection.
Figure 6
Figure 6
38 yo. Female received treatment on right side with CPM-HA B 22.5 mg/mL and left side with a CaHA-CPMB blend (CaHA with 1:1 dilution). US images performed 14 days after injection. (A) Right side, CMP-HA 22.5 mg/mL. (B) Left side CaHA-CPMB blend (CaHA with 1:1 dilution).
Figure 7
Figure 7
38 yo. Female received treatment on right side with CPM-HA B 22.5 mg/mL and left side with a CaHA-CPMB blend (CaHA with 1:1 dilution). CT scan 3D reconstruction image showing microdeposits of calcium in a linear trajectory in the left tear trough (black arrow).
Figure 8
Figure 8
38 yo. Female received treatment on right side with CPM-HA B 22.5 mg/mL and left side with a CaHA-CPMB blend (CaHA with 1:1 dilution). MR image showing microdeposits of hydrophilic filler were evidenced in the tear troughs in the supraperiosteal plane, predominantly on the right side.
Figure 9
Figure 9
38 yo. Female received treatment on right side with CPM-HA B 22.5 mg/mL and left side with a CaHA-CPMB blend (CaHA with 1:1 dilution). (A) Before. (B) 30 days after. (C) 60 days after. (D) 5 months after.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Woodward J, Cox SE, Kato K, Urdiales-Galvez F, Boyd C, Ashourian N. Infraorbital hollow rejuvenation: considerations, complications, and the contributions of midface volumization. Aesthet Surg J Open Forum. 2023;5:ojad016. doi: 10.1093/asjof/ojad016 - DOI - PMC - PubMed
    1. Aruan RR, Hutabarat H, Widodo AA, Firdiyono M, Wirawanty C, Double-blind FL. Randomized trial on the effectiveness of acetylhexapeptide-3 cream and palmitoyl pentapeptide-4 cream for crow’s feet. J Clin Aesthetic Dermatol. 2023;16(2):37–43. - PMC - PubMed
    1. Lee S, Yen MT. Nonsurgical rejuvenation of the eyelids with hyaluronic acid gel injections. Semin Plast Surg. 2017;31(1):17–21. doi: 10.1055/s-0037-1598189 - DOI - PMC - PubMed
    1. Kuruoglu D, Salinas CA, Kirk DS, Wong CH, Sharaf BA. Brow and eyelid rejuvenation: trends from the 100 most cited articles over 30 years. Medicina. 2023;59(2). doi: 10.3390/medicina59020230 - DOI - PMC - PubMed
    1. Love LP, Farrior EH. Periocular anatomy and aging. Facial Plast Surg Clin North Am. 2010;18(3):411–417. doi: 10.1016/j.fsc.2010.05.001 - DOI - PubMed

LinkOut - more resources