INTRODUCTION
Polydeoxyribonucleotide (PDRN) is derived from the sperm DNA of Oncorhynchus mykiss (salmon trout) or Oncorhynchus keta (chum salmon) and is well recognized for its tissue repair, antiischemic, and anti-inflammatory properties [1]. Platelet-rich plasma (PRP) is autologous plasma enriched with platelets and possesses significant tissue repair capacity [2]. Lower blepharoplasty is a frequently performed aesthetic procedure; however, complications such as ectropion occur more commonly in older patients, with weak lower lid support being a frequent contributing factor [3,4]. Although ectropion may result from excess skin removal, hematoma, swelling, or postoperative contracture, it generally resolves over time. Nonetheless, the condition can cause discomfort—manifesting as eye irritation and dryness—and may occasionally persist, leading to malposition [3-6]. Although several surgical techniques have been proposed to prevent ectropion [7,8], few treatments exist once the condition develops. Non-surgical methods, including taping, massage, and steroid injections, have been attempted; however, their outcomes remain inconclusive. In this study, we report the benefits of intradermal injections of PDRN and PRP for promoting scar regeneration and achieving rapid recovery from ectropion following lower blepharoplasty.
METHODS
Patients
This retrospective study was reviewed and approved by the Institutional Review Board of Hanyang University Medical Center (approval No. 2023-03-037). The study was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was obtained from all participants for the publication of identifiable photographs. We analyzed 21 cases of ectropion among 420 cases of transcutaneous lower blepharoplasty performed between January 2020 and October 2022. In all cases, skin excision was performed in a tension-free manner. Patients who underwent lateral canthoplasty, canthopexy, tarsal sling operations, or transconjunctival lower blepharoplasty were excluded. We retrospectively reviewed patient sex, age, history of lower blepharoplasty, comorbid conditions, smoking status, ectropion location, timing of injection initiation, intervals for additional injections, total injection count, patient satisfaction ratings, and follow-up duration. No patient was receiving steroids or immunosuppressants. Detailed patient information is provided in Table 1. Regarding preoperative evaluation, all patients underwent the pinch and snap-back tests. During surgery, the orbicularis oculi muscle was plicated along the lateral orbital rim to prevent postoperative ectropion.
Injection and follow-up
Patients were monitored for complications during outpatient visits held at 1-week intervals after lower blepharoplasty, and injection therapy was promptly administered when ectropion was observed. The injections were performed as standalone procedures, without any accompanying revision surgeries. Initially, 15 mL of blood—including 1.5 cc of anticoagulant—was collected from the patient’s arm. The blood was transferred to a kit (Ycellbio PRP; Ycellbio Medical Co. Ltd.) configured to contain 12.5 mL for women, 13.5 mL for men, and 14.5 mL for anemic patients. After 4 minutes of centrifugation, the buffy coat was extracted from the center of the kit using an adjustable lever, and 1.5–2.0 cc of PRP was collected with a long needle. The prepared PRP and PDRN (Placentex; PharmaResearch) were then uniformly injected intradermally into the lower eyelid using a 30-gauge needle. On each injection day, an additional 3 mL of PDRN was administered prior to the next outpatient follow-up at 1- or 2-week intervals. If symptoms persisted or if objective improvement was slow, additional injections of the combined PDRN and PRP therapy were administered using the described method. For patients who received multiple injections, the interval between injections ranged from 2 to 4 weeks, depending on symptom severity. All injections were performed by a single surgeon. Outpatient observation continued until ectropion was completely corrected—evidenced by the absence of symptoms and scleral show. Long-term follow-up examinations were conducted at 12 and 24 weeks, and patient satisfaction was assessed at 24 weeks using a 5-point scale (1, very dissatisfied; 2, dissatisfied; 3, neither satisfied nor dissatisfied; 4, satisfied; and 5, very satisfied).
RESULTS
The study included 12 female and nine male patients with a mean age of 62 years (range, 48–80 years). Patients presented with various underlying conditions, including diabetes mellitus in six, hypertension in eight, and hyperlipidemia in four cases. Furthermore, 15 patients underwent primary lower blepharoplasty, five underwent secondary procedures, and one underwent tertiary lower blepharoplasty. Five patients were current smokers, and all cases of ectropion were unilateral; 11 cases occurred on the left side and 10 on the right side. The first injection was administered 2 to 6 weeks after the onset of ectropion (mean, 3.8 weeks). Ten patients required only a single injection, all of whom developed symptoms after primary blepharoplasty. In contrast, 11 patients received two or more injections; this group included five patients with ectropion following primary lower blepharoplasty (45%), five with ectropion following secondary procedures (45%), and one with ectropion following tertiary surgery (9%). The mean time for complete ectropion improvement after injection was 9.3 weeks (range, 6–14 weeks). The average patient satisfaction score was 4.3 (range, 3–5), and the mean follow-up duration was 34.9 weeks (range, 24–52 weeks). At the final follow-up, all patients demonstrated complete resolution of ectropion. Detailed results are provided in Table 2.
Case 1
A 63-year-old male patient who had previously undergone two lower blepharoplasty procedures, but remained dissatisfied due to persistent eyelid bags, opted for a third transcutaneous lower blepharoplasty. He had diabetes and was on antihypertensive medication, with his condition relatively well controlled. Four weeks postoperatively, an outpatient visit revealed ectropion on the right side, and the patient reported discomfort. Consequently, one injection of PDRN and PRP was administered intradermally into the right lower eyelid. After 8 weeks, the symptoms had significantly improved, yet the lid position remained suboptimal; additional PDRN + PRP injections were then performed. A further injection was administered 12 weeks after surgery, leading to additional symptom improvement and correction of the ectropion by 14 weeks. At 20 weeks post-surgery, the fat bulging under the eyes improved symmetrically, resulting in a satisfactory outcome rated 4 (Fig. 1).
Case 2
A 68-year-old male patient with hyperlipidemia and no surgical history underwent transcutaneous lower blepharoplasty. During the procedure, there was neither excessive bleeding nor significant skin excision. However, in the third week postoperatively, the patient reported eye discomfort and asymmetry, prompting a clinic visit. On the same day, PDRN+PRP injection therapy was performed. At the 8-week follow-up, the patient’s symptoms had improved, and he experienced no discomfort; however, slight ectropion and lid position irregularities were noted on the left lower eyelid, warranting additional injections. By 12 weeks after injection, the eyelid had returned to normal and the ectropion had completely resolved. Despite undergoing two rounds of injection therapy, the patient achieved a high satisfaction score of 5 (Fig. 2).
DISCUSSION
The desire to appear younger and more attractive is universal across ages and ethnicities. With advancing age, gravitational effects contribute to fat bulging and reduced skin elasticity around the eyelids, resulting in an older appearance [3]. Numerous surgical methods have been developed to counter these changes, including the relatively straightforward lower blepharoplasty, which removes excess fat and sagging skin to rejuvenate the eye area [3-8]. However, this procedure carries a risk of complications such as ectropion, particularly in cases of significant lid laxity due to orbicularis oculi muscle denervation or excessive skin resection. Ectropion may also develop from postoperative hematoma or inflammation [6-8]. The frequent occurrence of ectropion following facial bone fracture surgery, even without excessive skin excision, illustrates that hematoma and traumatic traction can induce the condition [9,10]. Furthermore, heavy smokers may experience blood vessel constriction and an enhanced inflammatory response, leading to increased wrinkle formation. Various surgical techniques, such as lateral canthopexy, canthoplasty, sling operations, and the transconjunctival approach, have been modified to prevent ectropion in high-risk patients [4-7,11,12]. Despite these efforts, ectropion still occurs after standard lower blepharoplasty and fat repositioning, and although most cases eventually improve, the process may extend over several months [13], causing significant discomfort. Thus, prompt restoration of eyelid position is crucial to reduce discomfort and enhance satisfaction when complications arise. Previous non-surgical methods, such as taping, steroid injections, and massage, have demonstrated limited efficacy.
In this report, alongside the intraoperative plication of the orbicularis oculi muscle on the lateral orbital rim, we employed combined PDRN and PRP therapy to treat ectropion that had proven refractory to conservative methods, aiming for more rapid symptom resolution. PDRN and PRP have increasingly been used in cosmetic surgery to improve wrinkles and skin elasticity, facilitating a swift postoperative recovery. Both agents have shown promise in various clinical and molecular applications [14-23]; however, clinical data regarding their efficacy in resolving temporary ectropion following lower blepharoplasty remain limited.
As an adenosine A2A receptor (A2AR) agonist, PDRN promotes angiogenesis through vascular endothelial growth factor (VEGF) upregulation [17,18] and enhances tissue repair via fibroblast stimulation [14,19,20]. Activation of A2AR also yields anti-inflammatory effects by inhibiting several pro-inflammatory mediators [14-16]. Previous studies have highlighted three main beneficial roles of PDRN injections [14]: (1) increased collagen production, which reinforces the skin’s strength and elasticity; (2) reduced inflammation, thereby alleviating redness, swelling, and pain; and (3) accelerated wound healing through the promotion of angiogenesis.
At the molecular level, PRP injections release various growth factors—including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), VEGF, and insulin-like growth factor (IGF)—which are integral to cellular processes such as proliferation, differentiation, migration, and angiogenesis [21-23]. PDGF is a potent mitogen for mesenchymal cells involved in tissue repair and regeneration; TGF-β helps regulate the immune response and promotes extracellular matrix formation; VEGF is critical for angiogenesis; and IGF stimulates cell proliferation and differentiation [21-23].
Our preliminary trial in 21 cases yielded satisfactory outcomes, with an average patient satisfaction score of 4.3 and a mean ectropion resolution time of 9.3 weeks, considerably faster than the typical 3–6 months reported by previous experience [13]. These improvements are likely due to the enhanced collagen synthesis and anti-inflammatory effects of PDRN, as well as the tissue repair and angiogenic properties of PRP. Outpatient follow-ups were performed at 2- to 4-week intervals, and the time point for complete improvement was recorded; thus, the actual improvement period may be even faster than the average by 1–2 weeks. Moreover, patients reported significant symptomatic relief after even a single injection.
Among the 15 primary surgery cases, 10 responded well to a single injection. In contrast, all six patients with a history of multiple operations required two or more injections. In secondary surgery cases, the naturally more severe contraction and scarring necessitated additional injections, resulting in a slightly delayed resolution of ectropion compared to primary cases.
Despite these positive outcomes, certain factors may cause inconvenience or reluctance for patients, including the need for blood withdrawal and centrifugation for PRP preparation, additional costs associated with PDRN injections, and frequent outpatient follow-ups. Moreover, the retrospective design and small sample size of this study may introduce selection bias. The absence of a control group without injection therapy limits the ability to quantitatively compare improvements in ectropion. Although our results suggest that patients undergoing primary surgery respond more favorably to injection therapy than those with multiple lower blepharoplasties, the existence of a dose-response relationship remains uncertain. We ceased injection therapy once both subjective symptoms and objective signs of ectropion had resolved, and long-term outcomes did not substantially differ based on the number of injections. However, patients who required multiple injections experienced a longer overall recovery due to additional follow-up intervals. It is also challenging to determine whether the observed effects are attributable solely to PDRN or PRP. Nonetheless, this study is the first to combine PDRN and PRP for treating temporary ectropion after lower blepharoplasty, and our results may help shorten the period of postoperative discomfort. Given the benefits of these modalities in correcting post-blepharoplasty ectropion, these therapies might also play a role in its prevention. Further studies exploring their preventive effects could provide valuable insights for surgeons. We plan to continue refining complication rates through additional comparative studies, including investigations into the effects of PDRN or PRP when used individually.
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