No controlled study of exosomes applied to the under-eye area was located for this article: a 2026 systematic review of 16 facial studies and a 2026 meta-analysis whose 39 studies include 26 on skin report facial outcomes as a whole and name no periorbital subgroup [3, 4]. The skin there is the thinnest on the face, at 521 to 626 micrometers in one histological survey and a dermis of 759 micrometers at the upper medial eyelid in another, which is why the area is studied on its own terms [6, 7].
Patients asking about an under-eye add-on, and the staff who answer them, can work from four bodies of evidence: the anatomy of periorbital skin, the systematic reviews of PRP and PRF around the eye, the facial exosome studies, and the case reports that followed injection of exosome products in the face. Each is set out below, followed by the topical labeling position. ExaVeyra Sciences supplies exosome material to licensed practices; whether and how it is used is the practitioner’s decision.
Regulatory status
The FDA stated in its 2019 public safety notification that there are currently no FDA-approved exosome products, and its 2020 consumer alert, current as of 2024, repeats that statement [17, 18]. ExaVeyra supplies exosome material for topical aesthetic use by licensed practitioners, and for laboratory research and clinical research conducted under an IND, described by its available formats. The case reports in this article followed intradermal injection of products labeled for topical use, a route outside that labeling [14, 15]. Whether any product is used near a patient’s eyes, and how, is a decision for the licensed practitioner.
Understanding periorbital skin as the thinnest on the face
Chopra and colleagues measured full-thickness biopsies at 39 facial subunits from 10 cadaveric heads in 2015 and reported that the upper medial eyelid carried the thinnest dermis on the face at 758.9 micrometers, against 1,969.2 micrometers at the lower nasal sidewall [6]. Lee and Hwang surveyed 452 biopsies from 28 body regions in 2002 and reported eyelid skin among the thinnest anywhere, at 521 to 626 micrometers in total with an epidermis of 31 to 71 micrometers [7].
A dermis that thin sits close to the orbicularis muscle and the vessels beneath it, which is why the periocular area carries its own device literature and its own precautions. Bajaj and colleagues reviewed laser and energy-based device use around the eye in 2024, from pigmented and vascular lesions to infraorbital dark circles, and exosomes do not appear among the modalities they cover [16].
The anatomy matters for a second reason. Anything applied to the eyelid is a short distance from the ocular surface, so the handling of any topical material near the eye is a practitioner judgment the published exosome trials, which addressed the cheeks and the face as a whole, do not inform.
What the published reviews report about the causes of dark circles
Searches for exosomes for dark circles research begin with a classification problem. Vrcek and colleagues described infraorbital dark circles in 2016 as multifactorial, arising from deep facial anatomy, soft tissue change and the skin itself, and wrote that an understanding of the anatomy is central to evaluating them [9].
Michelle and colleagues systematically reviewed 39 studies of periorbital hyperpigmentation in 2021 and separated pigmentary, structural, vascular and mixed causes [8]. The authors reported that fillers and fat grafting address volume loss, that topical agents and peels address pigment, and that the quality of evidence across the field is low; exosomes are absent from the modalities they reviewed.
| Cause described in the reviews | What the reviews report | Source |
|---|---|---|
| Volume loss and tear trough shadow | Fillers and autologous fat grafting reported as most effective for this cause | Michelle 2021 [8] |
| Pigment in the skin | Topical agents and chemical peels reported as useful; lasers mildly to moderately so | Michelle 2021 [8] |
| Visible vessels through thin skin | Lasers reported as mildly to moderately beneficial | Michelle 2021 [8]; Vrcek 2016 [9] |
| Skin texture, fine lines and crepiness | PRF associated with improvement in 14 periorbital studies; PRF improvement often diminished by 6 months | Sollitto 2025 [1] |
An under-eye concern therefore has to be evaluated before any modality is chosen, and the evaluation belongs to the practitioner. The table is a map of the published literature on the causes, with no exosome entry because no exosome study has addressed any of them.
Periorbital PRP and PRF reviews report sessions, intervals and fading by six months
The autologous platelet products are the closest published comparison for anyone weighing exosomes vs PRF under eyes. Evans and colleagues pooled 19 studies with 455 patients in 2021 and reported a mean of 3 PRP sessions at mean intervals of 23 days, follow-up averaging 3 months, and higher satisfaction than saline and other controls across three randomized trials [2].
Sollitto and colleagues compared PRP with PRF across 14 periorbital studies in 2025 and reported that PRF was associated with improvement in texture, wrinkles and crepiness while PRP showed stronger evidence for pigmentation, with only mild transient adverse effects for either [1]. The authors also reported that PRF improvement often diminished by 6 months and concluded that the evidence does not support the superiority of one over the other.
Individual trials add texture. Kadry and colleagues randomized 30 adults with dark circles of mixed cause in 2023 and reported that 53 percent of the PRP group had no response, against 6.7 percent in the fat transfer group [10]. Wanitphakdeedecha and colleagues measured periorbital fine line, fold and wrinkle depth by instrument in 28 adults after three intradermal PRP sessions a month apart in 2026, the kind of named periorbital endpoint the exosome trials have yet to publish [11].
Recognizing what the evidence does not yet show
- No controlled study has measured exosomes applied to the under-eye area, so exosomes under eyes results exist only as part of whole-face outcomes [3, 4]
- The 2026 meta-analysis reports no periorbital subgroup, and the 2026 systematic review reports no eye-specific endpoint [3, 4]
- The only topical exosome report that names periorbital wrinkles is a company-authored safety study of a cosmetic prototype with no control arm in the abstract [12]
- No study compares exosomes with PRF or PRP around the eye, so the comparison rests on separate literatures with different routes and designs [1, 2]
- Knauer and colleagues reported that 20 commercial exosome products carried minimal information on isolation, processing or shelf life, so a finding with one product is not evidence for another [5]
- The case reports of harm followed intradermal injection in the face; no report describes topical application near the eye, which leaves that route unstudied rather than reassured [14, 15]
Those gaps set the tone for the rest of this article. Anything said about exosomes and the eye area is an inference from whole-face studies, and the practitioner is the person who decides whether that inference applies to a patient.
Exosome facial studies rarely isolate the eye area
Gaebe and colleagues reported in 2026 that most of the 16 facial studies they reviewed found improvement in at least one skin-quality outcome, with wrinkle severity, pigmentation, hydration and elasticity reported for the face as a whole and no serious adverse events [3]. Stack and colleagues pooled a 20.2 percent facial wrinkle reduction and 14.7 to 23.4 percent gains in other skin outcomes from the 26 skin studies within their 39-study meta-analysis, again without a periorbital subgroup [4].
Park GH and colleagues measured wrinkles, elasticity, hydration and pigmentation by instrument after microneedling in 28 adults in 2023 and reported greater gains on the exosome side, with no periorbital zone named in the abstract [13]. Lee and colleagues listed periorbital wrinkle reduction among the parameters assessed for a potato-derived vesicle cosmetic prototype in 2025, in a safety study whose first and senior authors were employed by the product company and whose abstract describes no control arm [12].
Knauer and colleagues concluded in 2026 that human studies of topical exosomes remain scarce, with much of the evidence extrapolated from preclinical models [5]. For a search on exosomes for eye wrinkles, the accurate summary is that the published trials measured the face and the eye area has not been studied on its own.
Case reports after injection of exosome products describe lasting harm
Park KY reported four adult women in 2025 who developed persistent erythema, nodules, granulomatous inflammation and scarring after intradermal injection of exosome-containing cosmetic products in nonclinical settings, with incomplete resolution in all four despite corticosteroids, laser and surgical removal [14]. The products were labeled for topical use, and the author described injection as outside that labeling.
AlBargawi reported a 38-year-old man in 2025 with painful ulcerated papules and dusky discoloration of both cheeks three days after multiple intradermal injections of a lyophilized exosome product, consistent with ischemic necrosis, followed by atrophic scarring with hyperpigmentation that three laser sessions improved only modestly [15]. The author stated that no exosome product is approved for dermal injection.
There are currently no FDA-approved exosome products, in the agency’s own words, first stated in 2019 after serious adverse events in Nebraska and repeated in its consumer alert, current as of 2024 [17, 18].
Neither report describes the eye area, and neither describes topical application, so they say nothing direct about an under-eye topical step. They do document what followed when a product labeled for topical use was injected into facial skin, and the thin, well-vascularized tissue under the eye is a place where that distinction carries weight.
Topical labeling and intended use govern how the material is described
The FDA states that whether a product is a cosmetic or a drug is determined by its intended use, established in part by the claims made for it [20]. That is why ExaVeyra describes exosome material by what it is, how it is documented and how access works, and names no condition, including dark circles, as something the material is for.
The FDA microneedling page states that the devices are authorized to improve the appearance of facial acne scars, facial wrinkles and abdominal scars in patients aged 22 or older, and that they are not approved for delivering cosmetics, topical medications, drugs or blood products into the skin [19]. An exosome under eye treatment, as the phrase appears in search, has no counterpart in that authorization or in the published trials, which the reviews examined for the face as a whole [3].
| Point of comparison | PRP and PRF around the eye | Exosome material |
|---|---|---|
| Source | Autologous, prepared from the patient’s own blood at the visit | Manufactured from a cell culture or a plant source, with sources varying across commercial products [5] |
| Route in the published studies | Intradermal injection, mean 3 sessions 23 days apart [2] | Topical application after microneedling or laser, in whole-face trials [3] |
| Eye-specific evidence | 19 PRP studies and 14 PRP-versus-PRF studies pooled [1, 2] | No controlled study of the eye area located; one company-authored prototype report [12] |
| Duration reported | PRF improvement often diminished by 6 months [1] | Follow-up in the facial studies was short, and no periorbital follow-up was located [3] |
| US regulatory position | Autologous blood product; device clearance governs the kits | No FDA-approved exosome products, per the agency [17, 18] |
The practitioner evaluates the under-eye concern and chooses the route
An under-eye concern is evaluated for its cause first, as the reviews describe, and the practitioner then chooses a modality with its own evidence around the eye [8, 9]. Where a practitioner elects to use exosome material topically after a facial procedure, the trials above describe the face as a whole, and the session record should note that the eye area is outside the published designs.
Each ExaVeyra vial carries its lot number, a certificate of analysis with serology exists for every lot, and the certificate, characterization panel and cold-chain records are available on request. Orders ship overnight frozen on dry ice and arrive in 1 to 3 business days, and the lot documents give the practice a written answer to what the product is.
Access works through a verified account. Anyone may ask the scientific team a question or apply without an NPI, NPI review takes 1 to 3 business days, and verification gives access to the practitioner portal, product documentation and pricing.
The eye area is one of the last places the exosome literature has reached, and that leaves room for well-designed studies with named periorbital endpoints like those the PRP trials already use. Practices that document their material and their visits carefully will be the first able to read those studies against their own records when they arrive.
Educational Disclaimer: This article is for educational purposes only and does not constitute medical or legal advice. It does not identify any material, compound, device setting or protocol as safe, effective or appropriate for any patient, and it is not intended to diagnose, treat, cure, or prevent any disease. Questions about a treatment belong with the reader’s own licensed provider. Exosome material is supplied for topical aesthetic use by licensed practitioners. No exosome product is FDA-approved for any use, and ExaVeyra Sciences makes no statement about administration, route, or outcome. Compounded medications are not FDA-approved. They are prepared by a 503A compounding pharmacy licensed by the Texas State Board of Pharmacy for an individual patient against that patient’s prescription, and are available to NPI-verified licensed practitioners only, in the states where the pharmacy is licensed. Product, device and brand names mentioned are trademarks of their respective owners and are used only to identify the products discussed. Their mention is not an endorsement, and those owners have not reviewed or endorsed this article. ExaVeyra Sciences is a supplier and takes no part in any diagnosis, treatment decision, or plan of care. Findings described are attributed to the peer-reviewed literature, trial registries and agencies cited. The content of these guides is provided for general informational purposes only. It does not constitute legal, medical, or regulatory advice, and does not establish that any particular product or practice is compliant. Regulatory requirements vary by state and depend on the circumstances of each practice. Each practitioner should consult their own legal counsel and the applicable state licensing boards before acting on anything stated here.
References
- 1.Sollitto CF, Narduzzi M, Wolinsky C. A Systematic Review of Platelet-Rich Plasma Versus Platelet-Rich Fibrin for Periorbital Rejuvenation. J Cosmet Dermatol. 2025;24(11):e70524. PMID 41190633. PMC12587466. doi:10.1111/jocd.70524PRISMA-guided systematic review of injectable PRP and PRF in the periorbital region; 14 studies. Carries in this article: PRF was associated with improvement in texture, wrinkles and crepiness while PRP showed stronger evidence for pigmentation, both reported only mild transient adverse effects, PRF improvement often diminished by 6 months, and the authors concluded the evidence does not support the superiority of either. Disclosure: the authors declared no conflicts of interest.
- 2.Evans AG, Ivanic MG, Botros MA, Pope RW, Halle BR, Glassman GE, et al. Rejuvenating the periorbital area using platelet-rich plasma: a systematic review and meta-analysis. Arch Dermatol Res. 2021;313(9):711-727. PMID 33433716. doi:10.1007/s00403-020-02173-zPRISMA systematic review and meta-analysis of PRP applied to periorbital wrinkles, hyperpigmentation and photoaging, searches to June 2019; 19 studies, 455 patients, 95 percent female. Carries in this article: a mean of 3 sessions at mean intervals of 23 days, follow-up averaging 3 months, and higher satisfaction than saline and other controls across 3 randomized trials. Disclosure: the authors call for future studies without industry sponsors; registration CRD42019135968.
- 3.Gaebe K, Lowe K, Bosnalie D, Khoury S, Villemure Poliquin N, Nichols A. Effectiveness and Safety of Extracellular Vesicle-Based Therapies for Nonsurgical Facial Rejuvenation: A Systematic Review. Facial Plast Surg Aesthet Med. 2026. Published online ahead of print. PMID 42487416. doi:10.1177/26893614261457879PRISMA systematic review with GRADE assessment, searches January 2000 to June 2025; 16 studies, 503 participants. Carries in this article: outcomes were reported for the face as a whole (wrinkle severity, pigmentation, hydration, elasticity, overall appearance), no serious adverse events were reported, and certainty was low or very low. Disclosure: academic authors (Canada); no conflict statement in the PubMed record.
- 4.Stack ER, Spongberg C, Braud SC, Stanton WN, Elway M. Clinical Advances in Exosome-Based Therapies for Aesthetic Medicine: A Systematic Review and Meta-analysis of Human Clinical Trials. Aesthet Surg J. 2026;46(12 Suppl 2):S13-S25. PMID 41800726. doi:10.1093/asj/sjaf178Systematic review and random-effects meta-analysis, searches to February 2025; 39 human studies. Carries in this article: pooled facial wrinkle reduction of 20.2 percent and pigmentation and other outcomes improved by 14.7 to 23.4 percent, with no periorbital subgroup reported and protocols described as nonstandardized. Disclosure: published in a journal supplement on exosomes; no funding statement in the PubMed record.
- 5.Knauer G, Chang A, Gupta A, Brownstone N, Mejia N, Bauman S, et al. Clinical Evidence and Commercial Landscape of Topical Exosomes for Skin Rejuvenation: A Scoping Review. Aesthet Surg J. 2026;46(11):NP148-NP157. PMID 42411735. doi:10.1093/asj/sjag141Scoping review of 18 human studies of topical exosomes plus a market survey of 20 commercial cosmetic products. Carries in this article: human studies remain scarce with much of the evidence extrapolated from preclinical models, and the products carried minimal information on isolation, processing or shelf life. Disclosure: academic authors (USA); no conflict statement in the PubMed record.
- 6.Chopra K, Calva D, Sosin M, Tadisina KK, Banda A, De La Cruz C, et al. A comprehensive examination of topographic thickness of skin in the human face. Aesthet Surg J. 2015;35(8):1007-1013. PMID 26508650. doi:10.1093/asj/sjv079Histological study of full-thickness punch biopsies at 39 facial subunits from 10 cadaveric heads. Carries in this article: the thinnest dermis on the face was the upper medial eyelid at 758.9 micrometers against 1,969.2 micrometers at the lower nasal sidewall, and the authors confirmed that eyelid skin is the thinnest in the face. Disclosure: none stated in the PubMed record.
- 7.Lee Y, Hwang K. Skin thickness of Korean adults. Surg Radiol Anat. 2002;24(3-4):183-189. PMID 12375070. doi:10.1007/s00276-002-0034-5Histological survey of 452 biopsies from 28 body regions in Korean adults. Carries in this article: total skin thickness ranged from 521 to 1,977 micrometers, with the eyelid among the thinnest sites at 521 to 626 micrometers and an epidermis of 31 to 71 micrometers there. Disclosure: non-US government research support listed in the PubMed record.
- 8.Michelle L, Pouldar Foulad D, Ekelem C, Saedi N, Mesinkovska NA. Treatments of Periorbital Hyperpigmentation: A Systematic Review. Dermatol Surg. 2021;47(1):70-74. PMID 32740208. doi:10.1097/DSS.0000000000002484Systematic review of the PubMed literature on periorbital hyperpigmentation; 39 studies. Carries in this article: the authors separate pigmentary, structural, vascular and mixed causes, report that fillers and fat grafting address volume loss while topical agents and peels address pigment, and note the scarcity of high-quality evidence. Exosomes do not appear among the modalities reviewed. Disclosure: none stated in the PubMed record.
- 9.Vrcek I, Ozgur O, Nakra T. Infraorbital Dark Circles: A Review of the Pathogenesis, Evaluation and Treatment. J Cutan Aesthet Surg. 2016;9(2):65-72. PMID 27398005. PMC4924417. doi:10.4103/0974-2077.184046Narrative review of the pathogenesis and evaluation of infraorbital dark circles. Carries in this article: the authors describe dark circles as multifactorial, arising from deep facial anatomy, soft tissue change and the skin itself, the reason an evaluation precedes any choice of modality. Disclosure: none stated in the PubMed record.
- 10.Kadry A, Gamal A, Alkhalifah A, Ibrahim SMA. Efficacy of Platelet-Rich Plasma Versus Autologous Fat Transfer With Nanofat in the Treatment of Infraorbital Dark Circles: A Single-Blinded Randomized Comparative Clinical Trial. Dermatol Surg. 2023;49(3):247-252. PMID 36735798. doi:10.1097/DSS.0000000000003697Single-blinded randomized comparative trial in adults with infraorbital dark circles of mixed cause; n = 30 in two equal groups. Carries in this article: in the PRP group 20 percent had an excellent response, 13 percent a moderate response and 53 percent no response, against 46.7 percent excellent in the fat transfer group, a reminder that an autologous injectable with a longer record showed modest results around the eye. Disclosure: none stated in the PubMed record.
- 11.Wanitphakdeedecha R, Ollero MPGCR, Bhorntarakcharoen W, Sittiwanaruk S, Phokai W, Woramongkol T, et al. Efficacy and safety of photothermal biomodulated platelet-rich plasma versus standard platelet-rich plasma for facial rejuvenation: a prospective split-face randomized study. Sci Rep. 2026;16(1):25017. PMID 42225690. PMC13462578. doi:10.1038/s41598-026-54310-9Prospective split-face randomized study of intradermal PRP preparations in Thai adults with photoaging; n = 28, three sessions at one-month intervals, follow-up at 1, 3 and 6 months. Carries in this article: periorbital fine line, fold and wrinkle depth measured by instrument as named endpoints, the kind of periorbital measurement the exosome trials have not yet published. Disclosure: medical writing assistance was provided by the device company; the authors declared no competing interests.
- 12.Lee Y, Mohamed RW, Yang S. Safety Profile of Solanum tuberosum-Derived Exosomes: Evidence from In Vitro Experiments and Human Skin Tests. Pharmaceuticals (Basel). 2025;18(4):458. PMID 40283895. PMC12030548. doi:10.3390/ph18040458Laboratory study of potato-derived vesicles with human skin irritation tests and cosmetic prototype assessments. Carries in this article: the only topical exosome report located that names periorbital wrinkle reduction as a measured parameter, in a cosmetic prototype with no control arm described in the abstract. Disclosure: two authors were employed by the company that makes the product.
- 13.Park GH, Kwon HH, Seok J, Yang SH, Lee J, Park BC, et al. Efficacy of combined treatment with human adipose tissue stem cell-derived exosome-containing solution and microneedling for facial skin aging: A 12-week prospective, randomized, split-face study. J Cosmet Dermatol. 2023;22(12):3418-3426. PMID 37377400. doi:10.1111/jocd.15872Prospective, randomized, split-face study over 12 weeks, three microneedling sessions three weeks apart with an exosome solution on one side and saline on the other (Korea); n = 28. Carries in this article: instrument-measured wrinkle, elasticity, hydration and pigmentation gains on the exosome side reported for the face, with no periorbital zone named in the abstract. Disclosure: National Research Foundation of Korea grants listed in the PubMed record.
- 14.Park KY. Adverse Reactions Following Intradermal Injection of Exosome-Based Formulations: A Case Series. J Cosmet Dermatol. 2025;24(10):e70520. PMID 41097876. PMC12528963. doi:10.1111/jocd.70520Case series of adult women after intradermal injection of exosome-containing cosmetic products in nonclinical settings (South Korea); n = 4. Carries in this article: persistent erythema, nodules, granulomatous inflammation and scarring, with incomplete resolution in all four despite corticosteroids, laser and surgery, after products labeled for topical use were injected. Disclosure: the author declared no conflicts of interest.
- 15.AlBargawi S. Necrosis Following Dermal Injection of Lyophilized Exosomes: A Case Report. J Cosmet Dermatol. 2025;24(8):e70387. PMID 40820962. PMC12359287. doi:10.1111/jocd.70387Case report of a 38-year-old man with ischemic necrosis of both cheeks three days after multiple intradermal injections of a lyophilized exosome product (Saudi Arabia). Carries in this article: eschar, atrophic scarring with hyperpigmentation and only modest improvement after three laser sessions, and the author’s statement that no exosome product is approved for dermal injection. Disclosure: the author declared no conflicts of interest.
- 16.Bajaj S, Orbuch D, Wang JV, Biesman BS, Geronemus RG. Interventional and device treatment of the periocular area. Clin Dermatol. 2024;42(4):360-372. PMID 38336142. doi:10.1016/j.clindermatol.2024.01.008Narrative review of laser and energy-based device use around the eye, including infraorbital dark circles and cosmetic rejuvenation. Carries in this article: the periocular area has its own device literature and its own precautions, and exosomes are absent from the modalities the authors review. Disclosure: the authors declared no conflicts of interest.
- 17.U.S. Food and Drug Administration. Public Safety Notification on Exosome Products. December 6, 2019 (content current as of 12/06/2019; verified 4 November 2026). https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/public-safety-notification-exosome-productsAgency safety notification (CBER). Carries in this article: the statement that there are currently no FDA-approved exosome products, the reports of serious adverse events in Nebraska after unapproved products marketed as containing exosomes, and that exosomes used to treat diseases and conditions in humans are regulated as drugs and biological products.
- 18.U.S. Food and Drug Administration. Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes. Issued July 22, 2020; content current as of 04/09/2024; verified 4 November 2026. https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/consumer-alert-regenerative-medicine-products-including-stem-cells-and-exosomesAgency consumer alert (CBER). Carries in this article: the repeated statement that there are currently no FDA-approved exosome products, and that the only approved stem cell products are cord blood-derived hematopoietic progenitor cells for disorders of blood production.
- 19.U.S. Food and Drug Administration. Microneedling Devices. Content current as of 10/15/2025; verified 4 November 2026. https://www.fda.gov/medical-devices/aesthetic-cosmetic-devices/microneedling-devicesAgency device information page (CDRH). Carries in this article: microneedling devices are authorized to improve the appearance of facial acne scars, facial wrinkles and abdominal scars in patients aged 22 or older, and the page states they are not approved for delivery of cosmetics, topical medications, drugs or blood products into the skin.
- 20.U.S. Food and Drug Administration. Is It a Cosmetic, a Drug, or Both? (Or Is It Soap?). Content current as of 09/11/2024; verified 4 November 2026. https://www.fda.gov/cosmetics/cosmetics-laws-regulations/it-cosmetic-drug-or-both-or-it-soapAgency guidance page on the FD&C Act definitions. Carries in this article: whether a product is a cosmetic or a drug is determined by its intended use, established in part by the claims made for it, which is why supplier copy describes the material and names no condition.