Platelet-Rich Plasma and Combination Therapies for Dry Eye Disease: Current Advances and Future Directions

Abstract

Background

Dry eye disease (DED), as one of the most prevalent ocular surface diseases, is a multifactorial disorder disrupting tear film homeostasis and ocular surface integrity, profoundly impacts patients’ quality of life. Conventional therapies such as artificial tears and anti-inflammatory agents provide transient relief but fail to address underlying pathological mechanisms and may induce complications with prolonged use.

Summary

Platelet-rich plasma (PRP), an autologous biologic agent enriched with growth factors (e.g., platelet-derived growth factor, transforming growth factor-β, epidermal growth factor), has emerged as a promising therapeutic strategy. PRP promotes corneal epithelial regeneration, reduces inflammation, and restores glandular function, offering a pathophysiologically targeted approach. Recent studies highlight synergistic benefits of combining PRP with agents like hyaluronic acid, stem cells, or nanomaterials, which enhance tear film stability and tissue repair. Despite encouraging preclinical and clinical outcomes, optimal protocols and long-term safety of PRP-based combination therapies remain under investigation.

Key Messages

This review synthesizes current evidence on PRP’s mechanisms, clinical efficacy, and innovative combinatorial approaches for DED, emphasizing the need for standardized trials to validate these strategies. Future integration of PRP with biologics, advanced materials, or laser therapies may revolutionize precision medicine in DED management.

Introduction

Dry eye disease (DED) is a common, chronic, and progressive ocular surface disease (OSD) affecting multiple factors of the eye [1]. Symptoms like dryness, burning, the feeling of a foreign body, and intermittent visual disturbances can significantly lower patients’ quality of life [2]. Individuals over 50, particularly women, long-term contact lens users, those with autoimmune diseases like Sjögren’s syndrome, and people who frequently use diuretics or antihistamines are more likely to develop DED [3]. Data indicate that DED affects approximately 5% of adults in the USA, while worldwide prevalence ranges from 5% to 50% [4, 5]. A comprehensive study conducted in the USA, France, Germany, Italy, Spain, the UK, and Japan found that DED significantly decreases work productivity, and this reduction in productivity imposes a substantial economic burden on social development, which varies by region [6]. In the past clinical treatment, for patients with mild DED, clinicians usually choose artificial tears and eye lubrication to relieve symptoms, while for patients with moderate or severe OSD, anti-inflammatory drugs such as steroids can only be used for treatment; nonetheless, the concern is that on the one hand, the above treatment is difficult to repair the damaged tissue, and on the other hand, long-term use of drugs such as steroids can produce serious consequences such as increased eye pressure and increased risk of eye surface infections [7, 8]. Given the worsening epidemic of DED, it is urgent to seek alternative treatments that are effective in the long term, have few side effects, and ensure safety.

Recently, platelet-rich plasma (PRP) has gained attention as a biological agent due to its abundance of anti-inflammatory and growth factors, as well as its ability to promote tissue repair [9]. PRP’s wound healing properties further support its therapeutic potential not only for DED but for a wide range of OSD [10]. Research indicates that platelet-derived growth factor (PDGF) and transforming growth factor (TGF) in PRP positively impact cell proliferation and migration. This promotes healing of the ocular surface tissue and enhances the biological environment, facilitating the regeneration of corneal epithelial cells and alleviating DED symptoms, and in extensive studies, researchers found that combining PRP with standard clinical treatments can enhance its efficacy while maintaining good feasibility and minimizing complications [11]. Evidence suggests that combining PRP with hyaluronic acid (HA) enhances tear adhesion and stability, significantly improving symptoms and quality of life for patients with DED [12]. Additionally, combining PRP with stem cell factors may enhance the treatment of DED by promoting tissue regeneration and repair [13].

In conclusion, PRP, a clinically available and effective biologic agent, has demonstrated considerable application value. When PRP is combined with other components, it can form a synergistic effect through various mechanisms to provide practical and effective treatment for DED, even OSD. However, current literature suggests that PRP combination therapy remains in the exploratory stage, requiring further clinical trials to verify its long-term efficacy and safety for broader clinical application. Thus, in this paper, we discuss the application of PRP in treating DED and highlight successful combination therapy cases, emphasizing the potential of PRP to enhance clinical interventions for DED.

PRP Components and PRP Application in Ophthalmology

PRP Components and Preparation

PRP is plasma that contains a high concentration of platelets, which are isolated from the individual’s own anticoagulated whole blood using in vitro centrifugation, the main component of PRP is the platelets, which become highly concentrated during preparation [14]. As a crucial component of whole blood, platelets are abundant in bioactive substances, particularly growth factors such as PDGF, TGF-β, insulin-like growth factor, epidermal growth factor (EGF), and vascular endothelial growth factor [15]. These growth factors play an important role in tissue repair and regeneration processes (shown in Fig. 1).

Fig. 1.

The central region of the figure depicts platelets, surrounded by a variety of bioactive factors. They are capable of producing, including PDGF, VEGF, IGF, TGF-β, EGF, and others. VEGF, vascular endothelial growth factor; IGF, insulin-like growth factor.

PRP typically requires activation before it can function effectively, and it can be divided into exogenous activation and endogenous activation according to the activation mode [16]. Exogenous activation encourages liquid PRP to transform into a PRP gel, and this process involves activating platelets in vitro using chemical or physical methods before the PRP is utilized to release growth factors [17]. This method of exogenous activation is particularly suitable for hard tissue injuries that require rapid repair. Thrombin and calcium chloride are considered as common activators because they can rapidly induce platelet degranulation to activate PRP [18]. Endogenous activation refers to the process wherein PRP, which has not been preactivated by calcium chloride or other exogenous activators, is injected into the body and subsequently activated by natural physiological agonists such as thrombin and collagen. This mode of activation results in a more gradual release of growth factors, making it particularly suitable for soft tissue repair [19, 20].

Currently, common methods for PRP preparation are mainly divided into two categories: apheresis preparation and whole blood preparation. The apheresis method involves connecting the patient to a blood cell separator via a separation tubing set, thereby establishing a continuous circulatory system capable of processing large volumes of blood. It accurately identifies and collects the platelet-rich layer while simultaneously returning other blood components such as red blood cells back to the patient. In contrast, the whole blood method requires drawing the necessary volume of whole blood into an anticoagulant-containing container. Through centrifugation, the blood components, including red blood cells, white blood cells, and platelets, are separated into distinct layers according to density, after which the PRP layer is collected [21, 22]. It must be pointed out that although the aforementioned apheresis method and the whole blood method represent two distinct preparation approaches, they ultimately rely on centrifugation to isolate the PRP layer. Furthermore, although PRP preparation significantly enriches the platelet concentration compared to whole blood, the current lack of standardized protocols and systems for PRP production leads to considerable variations in platelet concentration across preparations. These differences in enrichment levels can largely be attributed to variations in the centrifugation parameters or the separation systems used during the processing [23–25]. Studies indicate that in clinical practice, either one-step or two-step centrifugation methods can be employed for the preparation of PRP. One-step centrifugation typically yields about double the platelet content and is more commonly used in eye clinics [26]. In contrast, two-step centrifugation can achieve approximately five times the platelet content, and this is because when PRP is prepared by two-step centrifugal method, plasma containing platelets is usually separated from red blood cells with heavier gravity through one centrifugation, and then plasma containing platelet components is transferred to a new container for a second centrifugation, so that platelets can gather well at the bottom of the container, and allows more than half of the platelet-deficient plasma to be discarded as supernatant [23] (shown in Fig. 2).

Fig. 2.

Flowchart for the preparation of platelet-rich plasma (PRP) through a two-step centrifugation process. The schematic illustrates the procedural sequence: (1) whole blood (initial state), (2) first centrifugation, (3) supernatant collection after initial centrifugation, (4) serum preparation prior to secondary centrifugation, (5) second centrifugation, (6) final PRP product.

Application of PRP in Ophthalmology

When utilized in ophthalmology, PRP is commonly referred to as eye platelet-rich plasma. It is typically prepared by collecting 80–100 mL of whole blood from the patient under aseptic conditions via venipuncture, using 3.2% sodium citrate as an anticoagulant, followed by isolation through a one-step centrifugation process [26, 27]. Eye platelet-rich plasma is primarily used to treat OSD based on its biological properties that promote tissue healing and regeneration [28]. The application of PRP in ophthalmology is becoming more widespread, and it has been shown to play a significant therapeutic role in treating a spectrum of OSDs including DED, corneal ulcers, corneal burns, neurokeratitis, and other eye conditions [28–31]. As early as 2001, researchers have applied PRP as an auxiliary method in macular hole repair in eye surgery and achieved satisfactory therapeutic effect [32]. In a study on post-LASIK Ocular Surface syndrome, Javaloy et al. [33] demonstrated that PRP effectively promotes the healing of epithelial injuries. However, PRP does not positively affect the restoration of corneal sensitivity after this condition, so, they forward that PRP lacks the ability to stimulate basal nerve regeneration in this condition. Additionally, they hypothesized that the effectiveness of PRP in restoring corneal sensitivity may relate to corneal integrity and bioavailability, as other studies indicated that PRP positively influences peripheral nerve regeneration [34, 35]. In addition, the beneficial role of PRP in the treatment of corneal ulcers has also been reported by relevant studies. In the study of Alio et al. [36], 95% of corneal ulcers were significantly improved when PRP was applied to patients with corneal ulcers, and 85.7% of cases had no symptoms of eye discomfort and clinical feedback reports related to pain, inflammation, and ulcer healing have shown that the application of PRP can effectively improve the effect. Furthermore, studies have shown that PRP cannot only promote the proliferation and migration of corneal epithelial cells through the release of growth factors, accelerate the healing of the cornea, but also promote angiogenesis, improve the blood supply of the ocular surface, and further promote the physiological effects of eye tissue repair and regeneration [27].

Related Factors of DED and Its Pathophysiological Mechanism

The occurrence of DED is influenced by various factors, including environmental elements like dust, humidity, wind, and air pollution, as well as lifestyle choices such as a sedentary lifestyle, eye hygiene, and the use of electronic devices; sedentary, eye hygiene, electronic products, eye health, and other life factors; also, Besides systemic diseases like diabetes and Sjögren’s syndrome, factors such as anxiety, depression, age, gender, and hormone levels are also believed to be closely linked to the incidence of DED [5]. Currently, DED can be categorized into two types based on its pathogenesis: (1) aqueous-deficient DED, which occurs due to insufficient tear secretion and (2) evaporative DED, which arises from a weakened tear film lipid layer and increased tear evaporation. Compared with water deficiency DED, evaporative DED is more common. But most people have both types of DED [37]. In summary, the primary pathological feature of DED is the dysregulation of tear film homeostasis, this dysregulation can result from abnormalities in ocular structures, including goblet cells, the ocular surface, and eyelids, this condition can also lead to dysfunction in ocular glands, such as the lacrimal and meibomian glands, which are crucial for eye health [38, 39]. Research indicates that lacrimal gland secretion is affected by several factors, including neuroregulation, endocrine influences, and local inflammation, among which the balance of sympathetic nerve and parasympathetic nerve is crucial for the secretion of tears, the excitation of parasympathetic nerve can promote the secretion of lacrimal gland, while the sympathetic nerve plays an inhibitory role. The dysfunction of lacrimal glands caused by abnormal neural pathways can lead to insufficient tear secretion, which leads to the occurrence of DED [40]. Besides, ocular surface inflammation is also very important in the pathogenesis of DED because the ocular surface of patients with DED is usually accompanied by inflammatory response, which is manifested as the damage of ocular surface cells and the infiltration of inflammatory cells, cytokines and chemical mediators released by inflammatory cells, such as pro-inflammatory factors, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), can lead to the apoptosis of ocular surface cells and the decline of lacrimal gland function, and its content was positively correlated with the severity of DED [41]. Studies related to ocular surface inflammation promoting the progression of DED have shown that tear film hyperosmia can stimulate ocular surface inflammation and epithelial and goblet cell damage, which will further lead to abnormal tear film regulation and aggravate tear film hyperosmia, thus forming a vicious cycle and leading to more serious clinical consequences [5]. Based on this, various clinical methods such as corneal staining, lipid layer analysis, tear osmotic pressure, and ocular surface inflammation marker detection are often used for comprehensive diagnosis of DED and personalized treatment according to individual conditions [42].

Clinical Research on the Application of PRP in the Treatment of DED

The positive role of PRP in the treatment of DED is gradually being appreciated, and many studies have been successfully conducted and published before this. The results indicate that PRP can effectively alleviate symptoms of moderate to severe evaporative DED, hyposecretory DED, DED secondary to Sjögren’s syndrome, and DED due to neurotrophic keratitis. For instance, Alio et al. [36] found that 32.9% of patients had received local anti-inflammatory therapy prior to PRP treatment, but this showed no significant effects. After PRP treatment, patients reported significant improvements in their symptoms, Schirmer’s test scores showed notable increases, and Ocular Surface Disease Index (OSDI) scores significantly decreased, at the same time, the researchers found that PRP can play a good role in both evaporative DED and water deficiency DED; in a study related to severe lacrimal duct dysfunction with severe DED, Avila [47] found that when PRP was used to treat the disease, the volume of the lacrimal duct was significantly improved in all cases, the tear rupture time was prolonged, the eye staining was decreased, and no adverse reactions such as complications occurred in any patient; Murtaza et al. [43], in a study of DED due to tarsus dysfunction, showed that PRP use significantly increased tear meniscus height, first noninvasive break-up time, and average noninvasive break-up time and decreased Patient Subjective Assessment (PSA) scores [43–45].

In addition to evaluating the efficacy of PRP as a standalone treatment for DED, researchers have also undertaken comparative studies. These studies assess the effectiveness of PRP relative to traditional therapeutic options, such as HA or artificial tears, in managing DED symptoms. Their results indicate that PRP offers more effective treatment and improves patients’ subjective experiences [46–48]. All these studies confirm that PRP offers robust clinical support for DED treatment and effectively addresses issues that conventional treatments struggle with. Traditional treatments, such as artificial tears, have drawbacks, including the need for frequent administration and reduced efficacy with long-term use. Although PRP can avoid such problems to a certain extent, the Tear Film & Ocular Surface Society (TFOS) still recommends the application of PRP in the third step strategy for the treatment of DED diseases to achieve better efficacy [49]. In other aspects, the influence of PRP application and preservation methods on its effect has also drawn much attention. The study of Kwaku et al. [49] pointed out that for some eye diseases, administration by injection could not significantly improve the therapeutic effect, while administration by drip could significantly improve DED, tear quality, and other parameters. Therefore, it is worth noting that, the use of PRP in treatment needs to be selected according to the actual situation, such as the need to help tissue regeneration or when the main cause of DED is damage to the tear gland, the injection of the drug will be the most effective method of administration [49]. Regarding the influence of PRP storage on its component stability, Chanatip Metheetrairut pointed out in his study that some components of PRP, such as EGF, PDGF-AB, TGF-β1, and fibronectin, can be stable for at least 3 months at −20°C, the contents of EGF, PDGF-AB, and fibronectin in PRP were higher than the original concentration even when it was stored at 4°C for a short time, and EGF was also increased when it was stored at −20°C. The researchers speculated that this may be the result of platelet activation. These findings suggest that PRP may be more effective when used in cold storage or cryopreservation [50].

Advantages and Potential Application of PRP Combined with Other Ingredients for Clinical Disease Treatment

Drug combination refers to the use of two or more drugs with different mechanisms of action successively or together in the treatment, and the combined application of some drugs has been proven to play a better curative effect, the principle may include synergistic effect, overcoming drug resistance, reducing dose to reduce side effects [51]. Combination drugs have been widely used in the treatment of cancer diseases, infectious diseases, cardiovascular diseases, and other chronic diseases [52]. Since PRP was developed and demonstrated advantages in the clinic, more and more researchers have tried to combine the emerging PRP with traditional therapies to achieve better treatment results, and it is exciting to see that PRP has been reported to significantly improve patient symptoms in a variety of diseases when combined with other ingredients. In a review published by Paganelli et al. [53], it was reported that the combined application of PRP and adipose-derived stem cells (ADSCs) significantly improved discomfort symptoms such as pruritus and burning sensation in patients with lichen sclerosus, and no other adverse reactions were found in patients treated with PRP and ADSC, except for slight swelling or temporary pain at the injection site. In addition, relevant studies also have shown that PRP combined with ADSC treatment in the early stages of lichen sclerosus is more helpful. In another study, researchers utilized the chemical crosslinker 1,4-butanediol diglycidyl ether to interconnect HA molecules, forming a more stable, mechanically enhanced, and degradation-resistant mono-crosslinked HA. This modified hydrogel was then combined with PRP for the treatment of knee osteoarthritis. The results demonstrated that the combined application exerted synergistic therapeutic effects in managing osteoarthritic knees and were marked by significant improvements in Visual Analog Scale (VAS) pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne Index, and the results of the Single Leg Stance Test (SLS). Meanwhile, the researchers observed a temporal disparity in the efficacy of pain reduction measured by VAS scores between PRP monotherapy and the combination therapy of PRP with mono-crosslinked HA. Specifically, patients receiving PRP alone demonstrated more significant improvement in VAS pain scores during the early treatment phase. However, in long-term follow-up assessments, the combination of PRP and mono-crosslinked HA exhibited a superior ability to alleviate pain [54]. Similarly, the difference in duration of use was reported in another study by Dernek and Kesiktas [55], in which PRP combined with ozone was used to treat osteoarthritis, the results show that although PRP alone and PRP combined with ozone can improve patients’ symptoms and have no significant difference in pain relief, PRP alone and PRP combined with ozone show different effects in relieving stiffness and physical function at different application times. Regarding the alleviation of stiffness, the combination therapy of PRP and ozone demonstrated superior efficacy at the sixth month. With respect to functional improvement, the PRP-ozone group showed better outcomes at the third month. Notably, the researchers observed that as early as day 10 of treatment, the combined application of PRP and ozone effectively reduced pain perception and inflammatory symptoms at the injection site, suggesting that this synergistic approach may accelerate recovery [55]. The role of ozone in enhancing the therapeutic effect of PRP can be answered in a study by Inguscio et al. [56], which looked at the effects of ozone and procaine on platelets in PRP when treated alone or together with PRP, the research results show that ozone or procaine alone can increase the contents of EGF, IL-2, and INF-α in PRP, and when combined with the two can further stimulate the increase of contents. Meanwhile, ozone alone has no effect on the contents of IL-1β, IL-6, IL-10, and TNF-α. However, the application of procaine alone could significantly increase the content of these components in PRP, and the addition of ozone in the procaine treatment group could not significantly increase the content of these substances. Studies on the mechanism by which ozone and procaine affect various active factors in PRP show that both ozone and procaine can induce morphological and functional modifications of platelets in PRP and stimulate the release of active factors. In detail, ozone can cause the expansion and increase of platelet surface protruding and open tubule system and affect the content of active factors through the release pathway, although procaine can cause a decrease in the expansion of the open tubule system, and platelets indicate protrusions, it can induce a significant increase in the release of microvesicles, which affect the content of active factors through the secretion pathway [56]. In addition to the above-mentioned lichen sclerosus and osteoarthritis, PRP combined with other ingredients has also shown better efficacy in the treatment of androgenic alopecia, rotator cuff tear, endometrial injury, keloid, and other clinical diseases. These studies all show that PRP combined with other ingredients can play a synergistic role and improve the possibility of disease cure (shown in Table 1).

Table 1.

Examples of PRP combined application and its therapeutic effect

Disease	Ingredients to be used in combination	Combined effect	Article type	Reference
Lichen sclerosus	Adipose-derived stem cell	More effective, especially in the early stages	Review	Paganell et al. [53] (2023)
Knee osteoarthritis	Single crosslinked hyaluronan	1 month alone is more effective, but 6 months in combination is more effective	Research article	Sun et al. [54] (2021)
Osteoarthritis	Ozone	More effective and patients may recover faster	Research article	Dernek and Kesiktas [55] (2019)
Hip osteoarthritis	Hyaluronic acid	Combined application is more effective and lasts longer	Research article	Nouri et al. [57] (2022)
Partial-thickness rotator cuff tears	Vitamin C	The effect was similar, but the combination had a slight advantage in improving functional scores and pain	Research article	Mohammadivahedi et al. [58] (2024)
Rotator cuff injuries	Mesenchymal stem cells	Combined application is most effective	Research article	Han et al. [59] (2019)
Endometrium repair	Mesenchymal stem cells	The effect of combined application is more significant	Research article	Wang et al. [60] (2024)
Keloids	Triamcinolone acetonide	The combination is more effective and can reduce the side effects of drugs	Research article	Hewedy et al. [61] (2022)
Vitiligo	Latanoprost, CO2 laser	Latanoprost is more effective in combination with a small amount of CO2 and PRP	Research article	Omar et al. [62] (2024)
Facial melasma	Tranexamic acid	Combined application is more effective	Research article	Tawanwongsri et al. [63] (2024)
Venous ulcers	Umbilical cord mesenchymal stem cells	Combined application is more effective, and the ulcer is basically healed in 62 days	Case report	Jiao et al. [64] (2024)
Moderately damaged tendons	Broad-spectrum matrix metalloproteinase inhibitors	The combination is more effective and has better histological characteristics	Research article	Jafari et al. [65] (2019)
Androgenetic alopecia	Minoxidil	The combination is more effective and significantly increases hair density and patient satisfaction	Review	Kaiser et al. [66] (2023)

Research Progress of PRP Combined with Other Ingredients in the Treatment of DED

PRP Combined with HA in Treatment of Severe DED

HA is a kind of polymer acidic mucopolysaccharide composed of d-glucuronic acid and n-acetylglucosamine, which exists widely in human tissues [67]. HA is regarded as a conventional medicine for DED because of its excellent water retention and lubricity, which can form a stable water film on the eye surface and maintain the moisture of the eye [68]. However, although HA can alleviate DED to a certain extent, on the one hand, because its effect is only to lubricate the eye surface, it cannot solve the fundamental problem of the pathological mechanism of DED, and on the other hand, due to its frequent use as HA eye drops, its limited action time on the ocular surface leads to its low bioavailability and preservatives or other ingredients in the eye drops increase the possibility of adverse reactions in patients [69]. Thus, the limitations of using HA for treating DED are significant and cannot be overlooked. Based on this, researchers have combined HA with PRP, which has excellent biological activity and safety, for the treatment of DED in order to find a more effective treatment. In a clinical study by Avila et al. [47], 30 patients with severe DED were equally divided into a HA alone treatment group and a HA combined with PRP injection group. The results of the study showed that the tear volume and tear break-up time in the HA combined with PRP injection group were significantly increased, and the eye surface staining and OSDI score were significantly decreased, and the changes in the above clinical results were significantly better than those in the HA alone application group, indicating that the combined application of PRP and HA could effectively improve the therapeutic effect of HA. It is safe and effective in improving patients’ subjective feeling and tear quality, and it is promising as a new method to treat DED.

PRP Combined with Sacchachitin Treated by 2,2,6,6-Tetramethylpiperidine-1-Oxyl Oxidation in the Treatment of Severe DED

Composed mainly of chitin and β-1, 3-glucan, sacchachitin (SC) is a water-insoluble dry residue formed by Ganoderma lucidum after digestion by KOH and bleaching by NaClO [70]. SC has been reported to have a good ability to promote wound healing and corneal regeneration. As a catalyst, the 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO)-mediated reaction system enables the selective oxidation of SC, introducing carboxyl groups onto its surface. This process yields negatively charged nanofibers, which subsequently form a hydrophilic 3D gel network. For instance, the results of Chao et al. [71] demonstrated that nanofiber materials (TOSCNF) formed by TEMPO-oxidized SC can significantly improve epithelial tissue healing and effectively accelerate wound repair in diabetic patients, it even resembles normal skin tissue, the improved tissue repair capacity of this oxidized material may be due to its unique hydrogel structure, which serves as a cell scaffold, providing an optimal environment for cell growth and differentiation, thus accelerating tissue regeneration. It is precisely because of its special structure and function as described above that it is a potential substance that can be used to treat DED. Consequently, researchers like Hong-Liang Lin investigated the application of TOSCNF material in conjunction with PRP for treating DED, and the research results showed that the combined application of this oxidation material and PRP could increase the effect of PRP in the treatment of DED, especially when an appropriate concentration of the mixture is used to activate PRP. This approach significantly enhances the proliferation and migration of corneal epithelial cells, and such an improvement effect can make the wound healing rate up to 89% and can fully improve corneal durability [72]. These findings suggest that certain substances treated with TEMPO oxidation in combination with PRP may enhance the original efficacy of PRP to improve or accelerate the treatment of DED, although in this study, the researchers used in vitro cell binding rabbit animal models rather than clinical treatment data. However, this safe and efficient treatment method should arouse the attention of scientific researchers and promote its early application in clinical practice.

Conclusion

Previous studies have shown that PRP can play a positive role in the treatment of OSD and is safer and has fewer side effects than traditional methods, and is gradually developing into a new strategy for the treatment of these clinical conditions. Although studies confirm that combining PRP with traditional drugs enhances its therapeutic effects, research on combining PRP with other components is still exploratory. Reports on such combinations are scarce, apart from those involving PRP with HA or TEMPO-oxidized nanomaterials discussed in this paper. Some researchers have discovered that PRP enhances the survival and functionality of stem cells. Stem cells treated with PRP exhibit greater migration and proliferation in vitro, suggesting a new avenue for combining PRP with other components in treating DED [73]. In addition, the combined application of PRP may not be limited to this combination with drugs or new materials but can also be combined with other therapeutic means, such as laser therapy. Studies have shown that the combination of PRP and laser therapy can significantly improve the treatment effect of DED patients, patients who received PRP injection and laser therapy combined regimen, their eye symptoms and tear film stability are significantly improved [74].

In summary, the application of PRP in combination with other ingredients shows significant potential in the treatment of DED and holds promise for addressing other challenging ocular surface conditions. Through the in-depth study of its mechanism and clinical effect, we cannot only better understand its principle of action but also provide more targeted treatment of DED. Current findings suggest that PRP can improve symptoms and quality of life in patients with DED by promoting ocular surface tissue repair and regeneration. However, balancing the perspectives and findings of different studies remains a challenge. Therefore, future studies should systematically consider patients’ individual characteristics, disease progression, and comorbidities to optimize treatment, enhance efficacy, and draw more universal conclusions.

Acknowledgments

We would like to express our gratitude to the FigDraw online platform (https://www.figdraw.com/) for providing the drawing tools and resources.

Conflict of Interest Statement

The authors declare no conflicts of interest.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Ying Liu and Junnian Liu: data collection, manuscript drafting, initial manuscript review, and reference organization; Rongyi Cao: supervision, decision-making, and final manuscript approval.

Funding Statement

This study was not supported by any sponsor or funder.