Clinical Insights
Dark Circles and Under-Eye Puffiness
From clinical assessment to targeted periocular care
Understanding pigmentation, vascular visibility, structural shadowing and edema – and what these distinctions mean for treatment selection.
The eye contour is a small area. The clinical challenge is not.
Dark circles and under-eye bags describe an appearance, not a single diagnosis. Similar concerns can reflect different combinations of pigmentation, visible vasculature, skin characteristics, anatomical changes and fluid accumulation. Clinical classifications therefore distinguish contributing components rather than treating every dark circle as the same condition. [1,2]
For the clinician, the central question is which component should be treated, what change is realistic, and how the response will be measured. This article reviews selected research, offers a practical assessment framework and places EyeBelle peptide® within a clearly identified discussion of formulation rationale.
1. One appearance, several contributing factors
A useful assessment separates color, contour, skin quality and swelling. Pigmentary, vascular, structural and mixed categories are supported by clinical research. The framework below adds fluid-related puffiness as a distinct assessment question; it is an editorial synthesis, not a validated diagnostic score. [1,2,3]
| Predominant component | Findings that may guide assessment | The practical question |
|---|---|---|
| Pigmentary | Persistent brown discoloration, constitutional pigmentation or post-inflammatory change. | Is melanin the principal contributor, and is an inflammatory trigger still present? |
| Vascular / skin transparency | Blue or violaceous coloration, visible vessels and thin lower-eyelid skin. | How much of the appearance is vascular show-through? |
| Structural shadowing | Hollowing, protruding fat pads or an uneven lid-cheek junction. | Is the darkness a change in skin color or a shadow created by anatomy? |
| Edematous | Swelling requiring assessment of its distribution, time course and associated symptoms. | Is fluid accumulation involved, and what is causing it? |
| Mixed | More than one contributing feature. | Which component has the greatest impact, and which should be addressed first? |
Clinical synthesis of references 1–3. The categories overlap and are not diagnostic criteria.
In a cross-sectional study of 250 patients, Chhabra and colleagues classified 88.4% of presentations as mixed. That percentage describes the study population, not a universal prevalence; its value is to illustrate the limitations of a single-cause approach. [4]
Instrumental research has also associated dark circles with higher melanin and hemoglobin indices and thinner under-eye skin. These are associations, not proof that one factor explains every case. They nevertheless help explain why pigment reduction alone may leave other contributors unchanged. [3]
2. Clinical assessment before product selection
Look beyond the appearance of tiredness
A tired appearance does not establish the cause of a dark circle. A case-control study involving 303 participants found no significant difference in sleep-quality scores between people with and without periocular hyperchromia. This does not exclude every influence of sleep, but persistent discoloration should not simply be attributed to insufficient rest. [5]
A focused history should consider onset, progression, family history, irritation, atopy, rubbing, topical exposures and previous procedures. Clinical and histopathological investigations support a multifactorial assessment rather than one explanation for all patients. [1,6]
Examine pigmentation and inflammation separately
Dermoscopy may help distinguish pigmentary and vascular patterns and reveal subtle erythema or scaling. Chhabra and colleagues found additional information compared with unaided examination, but their study lacked histological correlation and a control group. Dermoscopy therefore complements the history and examination; it does not replace them. [4]
Ask what has already been done in the area
Previous filler treatment can remain relevant to swelling or discoloration. A retrospective study of 147 patients with at least five years of follow-up documented persistent malar edema, blue-gray discoloration and contour irregularities in some patients. Most recorded complications were mild. These findings do not establish the risk of every product or technique, but they reinforce the need to review prior treatments before adding another intervention. [7]
3. Three distinctions that change the treatment discussion
Pigmentation is not shadowing
A trial that improves infraorbital hollowing does not automatically demonstrate a depigmenting effect. The randomized study of VYC-15L evaluated an anatomical deficit. Its findings support interpretation of contour change, not a claim that filler treats every cause of under-eye darkness. [11]
Vascular visibility is not necessarily deposited blood pigment
Visible vasculature should not automatically be equated with extravasated blood, iron deposition or hemoglobin breakdown products. In a clinicopathological study of 50 patients, biopsies showed melanin-related changes and staining for hemosiderin was negative in every case. This does not exclude blood-derived pigments in other circumstances, but it argues against using them as a universal explanation. [6]
Edema, fat prolapse and hollowing are different targets
Huang and colleagues used ultrasound to distinguish increased preseptal thickness in patients with puffiness from protruding retroseptal fat in patients with bags. The teaching point is not that an appearance alone proves one cause: it is that similar concerns can have different underlying structures. [2]
A formulation intended for skin-related concerns should not be assumed to correct substantial fat prolapse or an anatomical hollow. Conversely, a contour-directed intervention may leave pigmentary or inflammatory contributors unchanged. Treatment planning should make that distinction explicit. [2,11]
4. Reading the treatment evidence in context
Research includes topical formulations, device-assisted protocols, fillers and regenerative interventions. The clinically useful comparison is not simply the percentage improvement reported: it is who was treated, what was measured, what the comparator was and how long follow-up lasted. The examples below are a selected evidence snapshot, not a ranking or a comprehensive treatment guideline.
| Approach and study | What was observed | What cannot be inferred |
|---|---|---|
| Multi-ingredient topical formulation Brady & Shah-Desai, 2025 [9] | An open-label study of 53 participants reported improved measured pigmentation after six weeks. | No control group; individual ingredient contributions and performance of other formulations were not established. |
| Laser plus topical treatment Momosawa et al., 2008 [10] | An 18-patient Japanese series reported improvement with a combined pigment-focused protocol. | Not a randomized comparison. Two patients developed post-inflammatory hyperpigmentation; results are not universal across skin types or devices. |
| Hyaluronic acid filler for hollowing Fabi et al., 2021 [11] | A multicenter randomized trial showed correction of infraorbital hollowing with a specific filler. | The target was anatomical. Recorded local reactions included swelling and bruising; the trial did not establish treatment of all dark circles. |
| Microneedling with selected agents Pazyar et al., 2025 [12] | A randomized split-face study of 37 women found improvement with tranexamic acid and vitamin C combinations, without a significant difference between them. | The design did not isolate the procedure from the active agent or validate arbitrary products for the same route. |
| Polynucleotides versus non-crosslinked HA Lee et al., 2022 [13] | In 27 participants, selected skin-quality measures favored the polynucleotide preparation. | Global aesthetic assessments were not significantly different. Results do not demonstrate superiority of all PN or PDRN products. |
| Platelet-rich plasma versus fibrin Behrangi et al., 2026 [14] | Twenty-four patients completed a randomized split-face comparison; several outcomes improved with both approaches. | No consistent overall clinical superiority. The sample was small and severe hollowing was not adequately corrected. |
| Topical PDRN preparation Ye et al., 2026 [15] | A 28-day split-face study in 31 women compared a defined PDRN eye cream with retinol. | Short-term preparation-specific findings do not establish durable remodeling or the performance of other PDRN-containing products. |
These studies do not show that established approaches fail. They show why benefits should be interpreted in relation to the target and the exact intervention. Different populations and endpoints make indirect comparisons of improvement percentages unreliable.
Several studies are small, uncontrolled, short-term or linked to commercial formulations. Their findings may be useful without resolving every clinical question. Most importantly, evidence for an ingredient, a combined protocol and a finished product represents three different levels of support.
5. Evaluating response beyond the before-and-after
A photograph is informative only when its conditions and timing are known. Mac-Mary and colleagues observed intra-individual, intra-day and inter-day variation in dark-circle intensity, supporting consistent conditions when documenting change. [3]
For clinical records, define the primary concern before treatment. Measure changes in pigmentation, puffiness, contour and texture separately rather than reducing them all to an overall impression of rejuvenation. The following is a practical documentation framework, not a validated scoring instrument.
| Record | Information that makes the result interpretable |
|---|---|
| Baseline | Predominant contributors, phototype, relevant history and previous procedures. |
| Intervention | Exact product and protocol, sessions and concurrent treatments. |
| Images | Comparable lighting, camera position, expression and framing; no retouching of the clinical result. |
| Timing | Time from the first and most recent session, with later follow-up where available. |
| Outcomes | The specific target assessed, not only an overall aesthetic impression. |
| Tolerability | Discomfort, irritation, swelling, adverse events and discontinuations, alongside satisfaction. |
Validated tools can strengthen this process. O’Mahony and colleagues developed a ten-point photonumeric dark-circle scale and assessed reproducibility, repeatability and sensitivity. Its validation supports a structured assessment of dark-circle severity, not automatic measurement of edema, hollowing or every periocular concern. [16]
The question is not only whether the area looks different, but what changed, whether it persisted and how the patient tolerated the intervention.
From assessment to treatment priorities
Once the predominant contributors have been identified, clinical assessment can be translated into explicit therapeutic objectives. The pathway below summarizes this sequence and shows where a multi-target periocular formulation such as EyeBelle may be considered within an individualized plan. It is a conceptual decision aid, not a validated diagnostic or treatment algorithm.
6. From clinical understanding to the EyeBelle formulation rationale
Manufacturer-supplied product information. Proposed mechanisms are distinguished below from independently demonstrated clinical performance.
Persebelle presents EyeBelle peptide® as a sterile bioactive formulation for professional periocular care. Its technical dossier focuses on dark circles and puffiness and organizes the formulation around five proposed routes of action. [20]
The dossier’s key-actives page lists Addwhite™ – tranexamic acid, Tranexamoyl-Dipeptide-23, α-arbutin and niacinamide – and Ophira™ – hesperidin, chrysin, glycyrrhizate and N-hydroxysuccinimide – alongside peptides, PDRN, hyaluronic acid and Complexia55™. This is a manufacturer description of selected ingredients, not a complete quantitative formula. [20]
Route 1 / Pigmentation-related pathways
The first proposed route concerns melanin synthesis and transfer. Niacinamide has been investigated in laboratory models and topical studies; Hakozaki and colleagues supported inhibition of melanosome transfer rather than direct tyrosinase inhibition in their experiments. [17,20]
Sugimoto and colleagues found reduced melanin production and cellular tyrosinase activity with α-arbutin in cultured cells and reconstructed skin. This is preclinical evidence, not a clinical response rate for patients with dark circles. Tranexamic-acid studies offer additional context, but none of these results can be assigned directly to EyeBelle or used to demonstrate synergy within it. [12,18]
Route 2 / Hemoglobin-derived discoloration
The dossier attributes a role to chrysin and N-hydroxysuccinimide in processes related to hemoglobin breakdown products. This proposal must remain distinct from the simple visibility of vessels through thin skin. [20]
Walle and colleagues showed induction of the bilirubin-conjugating enzyme UGT1A1 by chrysin in a human hepatoma cell line. That experiment did not demonstrate clearance of iron or blood-derived pigments from periocular skin. It provides biochemical background, not clinical proof of this proposed route in EyeBelle. [19]
Route 3 / Lower-eyelid skin support
The dossier describes support of thin lower-eyelid skin as a formulation objective. Research on particular PN and PDRN preparations provides context for investigating skin quality, but preparations and application methods differ. Appropriate outcomes would need to show what changed in the skin, separately from correction of hollowing or fat prolapse. [13,15,20]
Route 4 / Vascular and fluid-related pathways
The manufacturer’s framework associates hesperidin-related ingredients and dipeptide-2 with vascular permeability and fluid balance. These are proposed formulation targets. Clinical interpretation would require assessment of the source of swelling and outcomes able to distinguish fluid-related puffiness from structural bags. [2,20]
Route 5 / Swelling-related pathways
The fifth route links chrysin to inflammatory pathways associated with swelling. A proposed anti-inflammatory mechanism does not establish that all bags share one cause, or replace evaluation of active skin disease, unexplained edema or orbital symptoms. [4,8,20]
From formulation rationale to clinical practice
EyeBelle’s five-route framework brings together the formulation’s proposed biological targets for professional periocular care. The cited research provides scientific context for these targets and relates to the specific ingredients, preparations and experimental settings studied. Ingredient-level findings and clinical outcomes of the finished formulation should therefore be considered separately, with product-specific documentation guiding the assessment of efficacy and tolerability. [12,13,15,17,18,19,20]
In practice, individual patient assessment and carefully documented treatment experience help place this rationale in context. Recording baseline findings, treatment protocols, concomitant treatments and follow-up supports a considered interpretation of individual responses and realistic expectations. Clinical case observations complement this assessment; they do not, by themselves, establish comparative performance.
7. Defining an appropriate role in practice
For any professional formulation, the assessment should determine whether the intended application matches the individual’s predominant concern. A skin-directed rationale should not be presented as a substitute for correction of substantial fat prolapse or anatomical hollowing. Unexplained swelling also requires assessment rather than automatic treatment as an aesthetic indication. [2,8,11]
Persebelle’s Painless Beauty philosophy expresses an emphasis on patient comfort. It is not a guarantee of absent discomfort or adverse effects; these should be recorded for the actual product, application method and patient.
The product’s presentation as sterile does not, by itself, establish an authorized administration route. Clinical use must follow current instructions for use, product-specific documentation, local requirements and individual medical assessment. This article is not an injection or procedural protocol.
Precision begins with understanding the problem
Periocular care begins with the distinction between pigment, visible vasculature, anatomy and edema. The evidence supports careful selection and structured assessment, while leaving important questions about comparative effectiveness and durability unresolved. [1,2,3,4,9,10,11,12,13,14,15,16]
EyeBelle can be evaluated within that framework: through its stated formulation rationale, current professional documentation and appropriately recorded outcomes. The objective is not to treat every dark circle in the same way, but to make a targeted, defensible decision for each presentation.
References
Select a numbered citation to jump here. PubMed opens the bibliographic record; the journal link may require access. Free full text is identified where available.
- Ranu H, Thng S, Goh BK, Burger A, Goh CL. Periorbital hyperpigmentation in Asians: an epidemiologic study and a proposed classification. Dermatol Surg. 2011;37(9):1297-1303. DOI: 10.1111/j.1524-4725.2011.02065.x.
PubMed / Journal article / DOI - Huang YL, Chang SL, Ma L, Lee MC, Hu S. Clinical analysis and classification of dark eye circle. Int J Dermatol. 2014;53(2):164-170. DOI: 10.1111/j.1365-4632.2012.05701.x.
PubMed / Journal article / DOI - Mac-Mary S, Zornoza Solinis I, Predine O, et al. Identification of three key factors contributing to the aetiology of dark circles by clinical and instrumental assessments of the infraorbital region. Clin Cosmet Investig Dermatol. 2019;12:919-929. DOI: 10.2147/CCID.S217956.
PubMed / Journal article / DOI / Free full text - Chhabra N, Khare S, Sachdev D. Dermoscopy as an efficient aid to diagnose pigmentary and vascular component of periorbital melanosis: a cross-sectional study. J Cosmet Dermatol. 2022;21(11):5880-5886. DOI: 10.1111/jocd.15141.
PubMed / Journal article / DOI - Barone CR, et al. The influence of sleep quality on the development of periocular hyperchromia: a case-control study. J Cosmet Dermatol. 2020;19(7):1760-1767. DOI: 10.1111/jocd.13195.
PubMed / Journal article / DOI - Nayak CS, Giri AS, Zambare US. A study of clinicopathological correlation of periorbital hyperpigmentation. Indian Dermatol Online J. 2018;9(4):245-249. DOI: 10.4103/idoj.IDOJ_244_17.
PubMed / Journal article / DOI / Free full text - Mustak H, Fiaschetti D, Goldberg RA. Filling the periorbital hollows with hyaluronic acid gel: long-term review of outcomes and complications. J Cosmet Dermatol. 2018;17(4):611-616. DOI: 10.1111/jocd.12452.
PubMed / Journal article / DOI - American Academy of Ophthalmology. Orbital Cellulitis. EyeWiki. Accessed October 22, 2026.
Clinical reference - Brady RT, Shah-Desai S. Clinical efficacy of a novel topical formulation on periorbital dark circles: an objective analysis. J Cosmet Dermatol. 2025;24(7):e70326. DOI: 10.1111/jocd.70326.
Journal article / DOI / Free full text - Momosawa A, et al. Combined therapy using Q-switched ruby laser and bleaching treatment with tretinoin and hydroquinone for periorbital skin hyperpigmentation in Asians. Plast Reconstr Surg. 2008;121(1):282-288. DOI: 10.1097/01.prs.0000293869.00522.ec.
PubMed / Journal article / DOI - Fabi S, et al. A prospective, multicenter, single-blind, randomized, controlled study of VYC-15L, a hyaluronic acid filler, in adults for correction of infraorbital hollowing. Aesthet Surg J. 2021;41(11):NP1675-NP1685. DOI: 10.1093/asj/sjab308.
PubMed / Journal article / DOI / Free full text - Pazyar N, Badakhsh F, Yaghoobi R, Seyedtabib M. Comparing the efficiency of microneedling and tranexamic acid versus microneedling and vitamin C in the treatment of infraorbital hyperpigmentation. Adv Biomed Res. 2025;14:149. DOI: 10.4103/abr.abr_287_23.
PubMed / Journal article / DOI / Free full text - Lee YJ, et al. Comparison of the effects of polynucleotide and hyaluronic acid fillers on periocular rejuvenation: a randomized, double-blind, split-face trial. J Dermatolog Treat. 2022;33(1):254-260. DOI: 10.1080/09546634.2020.1748857.
PubMed / Journal article / DOI - Behrangi E, et al. Comparing the efficacy and safety of PRP and PRF on periorbital skin quality: a randomized split-face clinical trial. J Cosmet Dermatol. 2026;25(6):e70971. DOI: 10.1111/jocd.70971.
Journal article / DOI / Free full text - Ye R, Wang Q, Du L, Li L, Hu F. Topical medium-length PDRN enhances dermal extracellular matrix repair in photodamaged skin via PI3K-Akt/TGF-beta-regulated pathways. PLOS One. 2026;21(7):e0350905. DOI: 10.1371/journal.pone.0350905.
Journal article / DOI / Free full text - O’Mahony M, et al. A validated photonumeric scale for infraorbital dark circles and its application in evaluating the efficacy of a cosmetic treatment product in a split-face randomized clinical trial. Int J Cosmet Sci. 2021;43(1):48-56. DOI: 10.1111/ics.12668.
PubMed / Journal article / DOI / Free full text - Hakozaki T, et al. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br J Dermatol. 2002;147(1):20-31. DOI: 10.1046/j.1365-2133.2002.04834.x.
PubMed / Journal article / DOI - Sugimoto K, Nishimura T, Nomura K, Sugimoto K, Kuriki T. Inhibitory effects of alpha-arbutin on melanin synthesis in cultured human melanoma cells and a three-dimensional human skin model. Biol Pharm Bull. 2004;27(4):510-514. DOI: 10.1248/bpb.27.510.
PubMed / Journal article / DOI / Free full text - Walle T, Otake Y, Galijatovic A, Ritter JK, Walle UK. Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in the human hepatoma cell line Hep G2. Drug Metab Dispos. 2000;28(9):1077-1082.
PubMed - Persebelle. EyeBelle Technical Dossier. July 17, 2026. Manufacturer-supplied information, 26 pages. Key actives: p. 3; five-route overview: p. 4; proposed mechanisms: pp. 5-24. Not a peer-reviewed clinical study.
Public product page (not the dossier)
Editorial disclosure
Published by Persebelle for healthcare professionals. This is a narrative review of selected literature and manufacturer-supplied information, not a systematic review or an independent comparative evaluation of EyeBelle. Commercial product information is identified separately. Illustrative eye appearances and anatomical cutaways are AI-generated, schematic and not to scale; they are not clinical photographs, treatment results, an anatomical atlas or a procedural guide. Clinical care requires individual assessment and adherence to current product documentation and applicable requirements. Sources checked: October 22, 2026.
