Periorbital tissue is among the first facial regions to display visible signs of aging, given its role as a primary focal point of facial expression. Loss of infraorbital volume, incluiding the depression known as the tear trough, can diminish overall facial apperarance by producing an impression of tiredness or sadness which, in turn, may negatively affect self-steem and how atractive an individual is perceived to be by others.^1,2

In a study that examined the preferences of women seeking aesthetic medicine care, most respondents considered the infraorbital area to be one of the facial areas that bothered them the most. This area was also rated as the second and third facial area most likely to be treated in the 30- to 50-year-old group.³

One of the challenges when discussing the infraorbital area is the wide variation in terminology and definitions. The infraorbital groove refers to the curved or U-shaped depression beneath the eyes, which frequently has a dark coloration over it. The other grooves in the infraorbital region are the palpebromalar groove and the nasojugal groove (Figure 1).

The palpebromalar groove refers to the deep groove that extends approximately 2 cm downward and laterally from the inner canthus of the eye and is commonly seen at the junction of the eyelid and cheek. It comprises the medial third of the nasojugal groove and continues inferolaterally, which in some individuals may be seen visually as the midcheek groove.^4,5

During the aging process, skin physiology changes and eventually diminish metabolic processes and normal cellular activities; a process called chronoaging.

One of the first phenomena of skin aging are skin laxity and fine rhytides, which begin at approximately 35 years of age, although they may not become evident until later.The main exogenous factor is photodamage.

Laxity is strictly related to a reduction in collagen and elastin production. It is associated with alterations in the extracellular matrix, particularly with a decrease in the concentration of hyaluronic acid (HA).⁶

The use of stabilized hyaluronic acid hybrid complexes (Profhilo^®, IBSA, Lugano, Switzerland) has gained relevance in aesthetic medicine due to their ability to address skin laxity and optimize skin quality through a process of cellular bioremodeling. This mechanism is based on the interaction between keratinocytes and fibroblasts, which favors the synthesis and organization of extracellular matrix proteins.

Those effects are mediated by the activation of the CD44 receptor, induced by specific molecular weights of HA. Likewise, a significant increase in the production of type I and IV collagen, as well as elastin, has been observed in treated areas, contributing to dermal regeneration.⁷

The administration protocol for stabilized hyaluronic acid hybrid complexes (HCC-HA) follows a standardized regimen that includes two applications at a 30-day interval.

In each session, 64 mg of non-cross-linked HA are administered, composed of 50% (32 mg) low-molecular-weight HA (80-100 kDa), and 50% (32 mg) high-molecular-weight HA (1100-1400 kDa).

Application is peablrformed by means of 10 intradermal boluses of 0.2 mL each, using a prefilled syringe containing 2 mL of product.

In the case of the face, the injection points have been standardized into five specific points per hemiface, known as Bioesthetic Points (BAP).⁸

Aliaxin^® (IBSA) is a line of dermal fillers based on ultrapure HA, manufactured through a patented biofermentation process using Streptococcus zooepidemicus strains. Its low percentage of cross-linking (<10%) and the minimal level of BDDE residues (<0.1 ppm) allow more effective integration into tissues, reducing trauma and structural alterations compared with other fillers.⁹

The use of HA fillers for the management of aging of the periocular region has increased as an alternative to surgical procedures with minimal recovery time, low complication rates, and although HA is biodegradable and has limited immunogenic potential.

Nevertheless, fillers may migrate and persist longer than expected and produce edema given the difficult lymphatic drainage of the area.

For this reason, it is crucial to use high-purity HA and fillers with a high cohesivity index to prevent migration and improve tissue integration. Furthermore, a thorough knowledge of facial anatomy and safe injection techniques is essential.¹⁰

We hypothesized that the combined use of HA hybrid complexes and cross-linked cohesive HA would produce a synergistic improvement in the infraorbital area, addressing both skin quality through bioremodeling and structural volume loss through mechanical support.

Objective

To present a case series of infraorbital aging with fine rhytides in the lower eyelid, dark circles or displacement of the infraorbital fat pocket in order to demonstrate the efficacy and safety of an intervention procedure with ultrapure and cohesive HA in that specific area of the face in a prospective, non-comparative study.

Justification

Periorbital aging is one of the primary aesthetic concerns because of the central role of the eyes in facial expression and gaze; therefore, these alterations and signs of aging impact on the patients’quality of life. Treatment of dark circles requires detailed anatomical knowledge because many factors may contribute to their appearance.

Eyelid laxity is a disorder that can often go unnoticed, but may contribute to ocular surface pathology and worsen dry eye symptoms because blinking in these patients is less effective.

Genetics contributes to the presence of eyelid bags, but aging plays an important role due to displacement of the infraorbital fat pocket in the setting of bone resorption and ligamentous laxity of the periorbital area.

In this prospective, non-comparative case series, eleven patients (ten women and one man), who attended various private clinics seeking improvement in their infraorbital aging condition (from August to December 2025), were included. All patients signed an informed consent form. The mean age was 45 years.

Inclusion criteria

Patients with dark circles, fine infraorbital rhytides, and malar loss.

Exclusion criteria

Patients with autoimmune diseases, active lesions or infections in the treatment area, keloid scarring, uncontrolled diabetes or hypertension, pregnant women, or those who refuse to sign an informed consent form that includes permission to use their clinical photographs for academic purposes.

Evaluation

For patient assessment, the degree of dark circles was evaluated according to the Hirmand classification, which is a scale used to evaluate tear trough deformity and infraorbital depression. It is divided into three grades based on the severity of tissue atrophy and localized depression:

• Grade 1 (Mild). Slight depression in the tear trough without significant changes in malar fat volume. The skin and the underlying structure still retain good firmness and support. It is generally more evident with lateral lighting. It responds well to treatments with low-cross-linked HA.
• Grade 2 (Moderate). The tear trough depression is more evident and extends laterally toward the malar region. There may be some degree of skin thinning and loss of malar fat volume. More pronounced infraorbital shadows may be noticeable, giving an appearance of fatigue.
• Grade 3 (Severe). Deep tear trough depression with marked loss of volume in the underlying fat. Tissue flaccidity and greater visibility of the transition between the lower eyelid and the cheek. In some cases, protrusion of the infraorbital fat pads is observed.¹¹

Skin condition (fine rhytides and laxity) was assessed according to the modifiedFitzpatrick-Goldman scale¹²(Table 1) and the Leal Silva scale.

The Facial Laxity Rating Scale (FLRS), or Leal Silva scale, is a tool designed to evaluate laxity of the facial skin and soft tissues. It classifies laxity into 10 grades: Grade 0 represents absence of laxity, and grades 1 to 9 indicate a progressive degree of laxity. It also evaluates four distinctive signs in four facial regions¹³:

1. Upper face: eyelid folds
2. Midface: nasojugal folds
3. Lower face: jowls
4. Neck: neck profile

A Global Aesthetic Improvement Scale (GAIS) form was also included; the patients and the treating physicians answered it to treatment satisfaction. Descriptive statistical analysis was used to report the results.

At each visit, patients underwent directed questioning and physical examination of the treated area to actively assess for adverse events, including erythema, edema, ecchymosis, nodularity, or signs of vascular compromise.

Study Design

Three visits were conducted. At the first one (day 0), HCC-HA and Aliaxin GP^® were applied, and the following scales were performed:

• Hirmand to assess the degree of infraorbital aging;
• the modified Fitzpatrick-Goldman to assess the condition of the infraorbital skin;
• Leal Silva to assess facial tissue flaccidity;
• and the Likert to grade pain associated with the procedure.

At the second visit (day 30), the second dose of HCC-HA was applied and the Hirmand, modified Fitzpatrick-Goldman, and Leal Silva scales were performed, as well as the Likert scale and a patient GAIS questionnaire.

At the third visit (day 60), no procedure was performed, and the assessments from the second visit were repeated (except for the pain scale), plus a GAIS assessment by the treating physician.

Procedure and Products Used

Aliaxin GP®

Due to its rheology (with a G´ of 95, high cohesivity, a tan delta of 0.23, and a G´ of 0.16), it improves volume in the periocular area, which requires materials with high tissue adaptation in order to avoid undercorrection. Thanks to its cohesivity, gel migration is prevented and greater projection of the material is achieved due to the molecular weights of the HA.

Profhilo®

The eyelid skin is very thin (less than 1mm in thickness), making it especially vulnerable to photodamage and aging. Thus, based on the rheology and the naturally hybrid complex (NAHYCO) technology of this product —which forms hybrid complexes with multilevel action—, it provides hydration to the eyelid skin via its low-molecular-weight chains.

High-molecular-weight HA provides structural support and improves the extracellular matrix through increased tension, preserving the periorbital fat and the rest of the fat pads that interact dynamically with the major support ligaments of the midface.

Application Technique

Patients were evaluated in the seated position to objectively assess the displacement of periorbicular tissues. The depression zone was marked from the inner canthus to the mid-pupillary line, defining the start and end points of the dark-circle depression.

The HA filler was applied with a 22-G or 23-G×50 mm cannula. The entry point was established at the intersection of two lines: one extending from the nasal ala to the earlobe, and the other from the lateral canthus to the jowl. The cannula was introduced in the supraperiosteal plane, applying boluses followed by retroinjection between the boluses, following the trajectory beneath the tear trough ligament and the nasojugal groove.

Boluses of 0.05 to 0.3 mL are recommended to project the tissue according to the patient’s volume replacement needs. Smaller to larger amounts were applied during retroinjection, with the maximum volume targeted at the level of the mid-pupillary line). To ensure precision in application, elevating the cannula is recommended to project the tissue and identify its tip using the hand contralateral to the injecting hand (Figure 2).

For the HCC-HA application, the following marking was performed (Figure 3), derived from the BAP technique:

1. 0.2 mL at the level of the lateral ocular canthus over the zygomatictemporal junction, aiming to provide multilevel tissue tone to the temporal area —encompassing the lateral orbital fat pads and the lateral temporal region—, and achieving tension by means of the orbicular retaining ligament, the zygomaticocutaneous ligament, the inferior temporal septum, and the SMAS.
2. 0.2 mL at 45 degrees from the lateral ocular canthus over the zygomatic bone, aiming to provide firmness to the tissues comprising the main support area of the middle and lower thirds of the face. This preserves the superficial and deep fat pads, such as the deep medial cheek fat, the sub-orbicularis oculi fat (SOOF), and the retro-orbicularis oculi fat (ROOF).
3. 0.2 mL on the mid-pupillary line below the orbital rim to preserve fat of superficial and deep fat pads (such as the deep and superficial medial cheek fat, medial SOOF, and medial ROOF), which directly participate in the tension of the zygomatic-cutaneous ligaments.
4. 0.2 mL at the intersection of the mid-pupillary line with the line extending from the nasal ala to the tragus, providing support to the infraorbital fatty tissue and the nasolabial fatty tissue.
5. 0.2mL at 5cm at the level of the tragus below the zygomaticotemporal suture, aimed at preserving the fat beneath the zygomaticocutaneous ligament, improving tissue tone within the SMAS, and enhancing the tension of the superior portion of the masseteric ligament.

No adverse events were reported in the patients in this study.

Patient satisfaction, evaluated by the GAIS scale, was rated as very positive in 82% of the cases and positive in 18%. The physician’s GAIS rating at the end of treatment showed an 82% very positive and 18% positive.

In the modified Fitzpatrick-Goldman grading (to measure elastosis):

• An initial grading of 36% of patients with grade 3 (severe elastosis) and 9% with grade 2 (moderate elastosis) was obtained; the rest of the patients initially had a grade 1 score (mild elastosis).
• At the second visit, 18% had a grade 3 score and the rest (82%) had grade 1. These scores were maintained at visit 3 (Graphic 1).

According to the Leal Silva scale for facial tissue laxity:

• At the initial visit, 91% of patients presented with moderate laxity and 9% with mild laxity.
• At the second visit, 27% showed moderate laxity and 73% mild laxity.
• By visit 3, moderate laxity had decreased to 18% and mild laxity was 82% (Graphic 2).

The Hirmand scale, which grades the condition of the infraorbital region, showed:

• At visit 1, that 45% of the patientes were type II (moderate) and 55% were type III (severe).
• At visit 2, 9% were type III, 55% were type II, and 36% were type I (mild).
• At the third visit, 45% were graded as type II and 55% as type I (Graphic 3).

Photograph 1 shows the patient before and after the procedure.

The findings of this study support the efficacy and safety of the combined approach using ultrapure cross-linked hyaluronic acid and HCC-HA for the treatment of infraorbital aging.

The improvements observed on the three scales used (Hirmand, modified Fitzpatrick-Goldman, and Leal Silva) reflect not only an improvement in the appearance of dark circles and tissue laxity, but also in the overall quality of the periorbital skin.

This multilevel approach enables action across different tissue layers, with HCC-HA acting as a tissue biomodulator and the ultrapure HA filler providing structural restoration through its high cohesivity and projection capacity. This synergistic effect appears to offer an effective alternative to more invasive procedures, with a high safety profile and no adverse events reported.

The level of satisfaction among patients and treating physicians, assessed through the GAIS scale, was notably high. This suggests that the treatment not only meets objective clinical criteria but also exerts a positive impact on the patient’s aesthetic perception.

Although the sample size is limited and the study was non-comparative, the promising results pave the way for larger, controlled studies that validate this technique as a standard therapeutic option in the management of infraorbital aging.