Medical Policy

This document addresses the use of topical continuous diffusion of oxygen therapy (for example, the EO₂ [formerly the TransCu O₂ System], and the OxyGeni^® System [with OxySpur^® dressing] EO2 Concepts^®, San Antonio, TX) which have been proposed to deliver continuous, low-flow oxygen directly to a wound through a small, wearable generator connected to tubing and a dressing. The oxygen is provided at normal atmospheric pressure, and is not hyperbaric therapy.

Note: For more information, please see the following related documents.

• CG-DME 18 Home Oxygen Therapy
• CG-DME 48 Vacuum Assisted Wound Therapy in the Outpatient Setting
• CG-MED 71 Chronic Wound Care in the Home or Outpatient Setting
• CG-MED 73 Hyperbaric Oxygen Therapy (Systemic/Topical)
• MED.00096 Low-Frequency Ultrasound Therapy for Wound Management

Note: For a high-level overview of this document, please see “Summary for Members and Families” below. 

Investigational and Not Medically Necessary:

The use of topical continuous diffusion of oxygen therapy is considered investigational and not medically necessary for all indications.

This document describes clinical studies and expert recommendations, and explains whether topical continuous diffusion of oxygen therapy is clinically appropriate. The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

Topical continuous diffusion of oxygen therapy (CDO), including use of devices such as EO2 (formerly TransCu O2) and OxyGeni (OxySpur dressing), is a type of wound treatment that delivers a steady flow of oxygen directly to a wound through a small wearable device. The oxygen is given at normal air pressure, not in a pressurized chamber like in hyperbaric therapy. This treatment is used along with standard wound care, not by itself. The goal is to help wounds heal by increasing oxygen at the wound site. Studies suggest that CDO may help some wounds heal faster in the short term. However, results have been mixed, and many studies had important limits, such as small numbers of participants, short follow-up periods, differences in treatment methods, and possible bias. More research is needed to know whether CDO improves long-term health outcomes and wound healing compared with standard wound care.

What the Studies Show

CDO is proposed to work by increasing oxygen levels in the wound. Oxygen helps the body repair tissue, build new blood vessels, and fight infection. Some studies show that wounds treated with CDO close faster or shrink more in the first few weeks compared to standard care alone. For example, several clinical trials found higher wound closure rates and shorter healing times with CDO. Some studies also show improved oxygen levels and healing signals in the tissue. However, other studies found little or no difference in long-term healing. This suggests that CDO may speed up early healing but may not change the final outcome.

There are important limits to the research. Some studies found little or no difference in healing compared with standard care. Many studies included small groups of people that make it difficult to apply the results to a wider population, had short follow-up periods so it is difficult to tell if the result last over time, or used different treatment methods, making results difficult to compare results from study to study. Some studies may have bias due to funding or study design. Several reviews found that while CDO may speed up early healing, it has not been clearly shown to improve long-term healing outcomes. Better studies are needed to know if CDO improves health.

Is this Clinically Appropriate?

Topical continuous diffusion of oxygen therapy is not clinically appropriate because it has not been proven to improve health.

Studies suggest that CDO may help some wounds heal faster in the short term. However, research results have been inconsistent. Many studies had important limitations, including small numbers of participants, short follow-up periods, differences in wound types and treatment methods, and possible bias. Several reviews found uncertainty about whether benefits last over time. Better studies are needed to know if CDO improves health.

Because the available research does not clearly show lasting health benefits, topical continuous diffusion of oxygen therapy is considered investigational and not medically necessary for all uses.

(Return to Description/Scope)

Summary

Topical continuous diffusion of oxygen (CDO) therapy is intended to deliver low-flow oxygen directly to wounds at atmospheric pressure via a wearable system as an adjunct to standard wound care. Evidence from randomized trials and meta-analyses suggests these devices may accelerate early wound healing and improve short-term closure rates, though results are variable and often depend on wound type, study design, and concurrent care. Limitations across the evidence base include small sample sizes, short follow-up periods, heterogeneity in protocols, and potential bias, resulting in uncertainty regarding long-term outcomes and generalizability. Current Wound Healing Society (WHS) guidelines emphasize established standards of care for chronic wounds (for example, debridement, infection control, moisture balance) (Federman, 2024; Gould, 2024; Kirsner, 2016; Lavery, 2024; Marston, 2016). The guidelines acknowledge that oxygen may play a role in wound healing; however, they do not specifically address or recommend topical continuous diffusion oxygen therapy devices. Rather, the available recommendations primarily discuss the use of hyperbaric oxygen therapy in selected wound care settings.

Discussion

In 2017, Niederauer published a randomized, double-blind, sham-controlled multicenter trial (n=100) that evaluated CDO therapy for chronic diabetic foot ulcers over 12 weeks. A significantly greater proportion of wounds achieved complete closure with CDO compared to sham moist wound therapy (46% vs. 22%, p=0.02), along with faster rates of healing (p<0.001), and enhanced benefit in more chronic wounds (e.g., 42.5% vs. 13.5%, p=0.006). Treatment effects were maintained across increasing wound size and appeared more pronounced in harder-to-heal ulcers, supporting a dose-response relationship between wound severity and benefit. Limitations include modest sample size, per-protocol analysis (excluding some randomized participants), relatively short follow-up (12 weeks), and potential industry funding and conflict of interest, which may introduce bias and limit generalizability despite the rigorous study design.

Niederauer (2018) followed up by reporting on a double-blind, placebo-controlled randomized multicenter trial (n=146) that evaluated CDO therapy for diabetic foot ulcers over 12 weeks using an intention-to-treat analysis. CDO significantly improved complete wound closure rates compared with placebo (32.4% vs. 16.7%, p=0.033), with similar findings in completed cases (46.2% vs. 22.6%, p=0.016), and significantly reduced time to healing (e.g., time to 50% closure: 18.4 vs. 28.9 days, p=0.001). Treatment effects were more pronounced in more chronic wounds (relative performance up to 334%) and in weight-bearing ulcers (closure 46.5% vs. 10.0%, p=0.002), while adverse events were similar overall but less severe in the CDO group. Limitations include relatively modest sample size, strict inclusion criteria limiting generalizability, short follow-up for durability outcomes, and potential conflicts of interest, as well as limited power for subgroup analyses despite rigorous blinding and study design.

A narrative review by Oropallo (2021) describes the physiological and molecular mechanisms by which oxygen therapies, including CDO, may enhance healing in diabetic foot ulcers, emphasizing oxygen’s role in cellular metabolism, collagen synthesis, angiogenesis, and immune function. Oxygen availability increases reactive oxygen species (ROS) production, which drives growth factor signaling (for example, vascular endothelial growth factor [VEGF], platelet-derived growth factor [PDGF]) and promotes angiogenesis, while also supporting collagen formation and tensile strength through oxygen-dependent enzymatic processes. A small prospective study (n=23) demonstrated that CDO significantly increased growth factors (up to 280 to 820% above baseline) and cytokines (up to 680% compared to baseline) within the first 1-2 weeks, along with improved tissue oxygenation, suggesting a biologic effect on wound healing pathways. Limitations include that the evidence is largely mechanistic and observational, with limited high-quality clinical outcome data, small sample sizes, and potential conflicts of interest, and it remains unclear how these biomarker changes translate into consistent, generalizable improvements in long-term healing outcomes. Large-scale randomized controlled trials are needed to confirm clinical efficacy and generalizability.

A 2021 narrative review by Frykberg describes topical oxygen therapy (TOT), including CDO and pressurized systems, as an adjunctive treatment for chronic diabetic foot ulcers, emphasizing oxygen’s role in reversing wound hypoxia and supporting key healing processes such as angiogenesis, collagen synthesis, and bacterial defense. There are three types of delivery systems for TOT. They are continuous delivery of oxygen systems (TransCu O₂), low constant pressure in a contained chamber system (Natrox^®, Inotec AMD Ltd., Cambridge, Cambridgeshire, England, UK) and cyclically pressurized and humidified in a contained chamber (TWO₂^®, Advanced Oxygen Therapy Inc., Oceanside, CA). The latter two types are considered hyperbaric therapy due to the oxygen delivery at higher than normal atmospheric pressure. The review summarizes multiple clinical studies, including randomized controlled trials, reporting improved healing rates with topical oxygen compared to standard care (e.g., 32.4% vs. 17.7%, p=0.033 for 1 CDO [TransCu O₂] trial; 44.4% vs. 28.1%, p=0.044 in another [Natrox]; and 41.7% vs. 13.5%, p=0.007 for a pressurized system [TWO₂]), along with faster time to closure and potential reductions in amputations. Findings are inconsistent across devices and trials, with at least 1 well-conducted RCT showing no significant difference (53.8% vs. 49.2%, p=0.42). Limitations include that the evidence base is heterogeneous, with variability across device types, study designs (including small or non-randomized studies), and mixed results (for example, some trials showing no significant benefit), and the therapy remains dependent on concurrent optimal wound care and appropriate participant selection. There were high dropout rates in the trials (up to 30%). Overall, while supportive evidence is growing, limitations include inconsistent trial quality, potential bias, and lack of standardized protocols, which restrict generalizability and lessen the strength of conclusions.

A feasibility pilot randomized controlled trial (n=16 participants; 32 breasts) evaluated CDO as an adjunct to standard care following reduction mammoplasty, focusing on feasibility, safety, tissue oxygenation, and wound outcomes (Zulbaran-Rojas, 2023). The intervention demonstrated high feasibility (93.7% protocol delivery), excellent acceptability (85.4% positive user attitude), and no device-related adverse events, while the silicon-covered CDO group showed significantly improved tissue oxygenation (higher SatO₂ and lower deoxyhemoglobin, p<0.001) compared to standard care. However, there was no significant difference in wound dehiscence rates between groups (0-12.5%, p=0.66), and results were limited by small sample size, short follow-up (4 weeks), and variability in measurement techniques. Overall, while CDO appears safe and capable of improving local tissue oxygenation, its impact on clinically meaningful outcomes such as wound breakdown remains uncertain and requires larger trials.

In 2021, Zulbaran-Rojas reported on a proof-of-concept randomized controlled trial (n=21, with 16 completing follow-up) that evaluated CDO as an adjunct therapy for scar reduction following cervicotomy. At 4 weeks, a significantly higher proportion of participants in the CDO group achieved greater than 10% scar reduction compared to standard care (88.8% vs. 28.5%, p=0.049), although the overall reduction in scar length did not reach statistical significance (15.7% vs. 11.2%, p=0.72). A subgroup analysis in thyroidectomy cases showed a significant improvement with CDO (11.6% vs. 5.1%, p=0.009), while no benefit was observed in parathyroid cases. Tissue oxygenation (SatO₂) did not differ significantly between groups, suggesting that mechanisms beyond measurable perfusion may contribute to scar outcomes. Limitations include small sample size, high attrition, short follow-up, potential confounding factors (for example, age differences, perioperative vasoconstrictors), and limited power for subgroup analyses, restricting generalizability and definitive conclusions.

In a systematic review and meta-analysis of 31 randomized controlled trials (n=1823), CDO is described as a topical oxygen modality delivering low-flow oxygen (approximately 3-10 mL/h) directly to the wound under a dressing, and is included among oxygen-based therapies shown to improve short-term wound healing outcomes (Du, 2024). Although results were not always isolated by modality, pooled analyses suggest oxygen therapies (including CDO) contribute to improved short-term healing rates (risk ratio [RR] 1.54), greater ulcer size reduction (standardized mean difference [SMD], 0.999), faster healing, and increased tissue oxygenation (transcutaneous partial pressure of oxygen [TcPO₂]), supporting a biologically plausible benefit of continuous local oxygen delivery. However, limitations specific to interpreting CDO include the lack of modality-specific subgroup analysis, small number of CDO-only trials (5 of 31), heterogeneity in treatment protocols and measurement timing, and overall study limitations such as risk of bias, lack of blinding, and inconsistent control groups. Additionally, no significant benefit was observed for long-term healing outcomes, suggesting that while CDO may accelerate early healing processes, its sustained clinical impact remains uncertain.

In 2025, Mercurio reported on an observational cohort analysis of a prospective real-world database (n=764 compliant individuals) that evaluated CDO therapy across multiple chronic wound types and compared outcomes to negative pressure wound therapy (NPWT). CDO demonstrated a high overall healing rate of 76.3% (range 71.2-84.1% by wound type), with Kaplan-Meier analysis showing 79.2% complete closure at 112 days compared to 43.2% with NPWT, and a shorter median time to healing (58 vs. 96 days), suggesting faster and more frequent wound closure with CDO. Results were consistent across age groups, wound types, and anatomical locations, and no serious adverse events were reported. However, limitations include the non-randomized observational design, potential selection and confounding bias, lack of standardized control for comorbidities and wound severity, missing data (including loss to follow-up), and indirect comparison to NPWT using separate datasets rather than head-to-head randomization, which limits causal inference despite statistical robustness.

A retrospective case series by Kormylo in 2025 evaluated the use of continuous topical oxygen therapy (cTOT) as an adjunct to standard of care in the treatment of lower-extremity surgical wound dehiscence (SWD), a complication characterized by separation of a surgical incision and associated with significant morbidity. Over an 8-month period, 9 individuals with grade 3 or 4 SWD received standard wound care alongside cTOT, resulting in complete wound closure in all cases without the need for additional surgery or hospitalization. The average healing time was approximately 70 days (59.5 days excluding an outlier), suggesting favorable outcomes even in the presence of comorbidities such as diabetes and smoking. The findings support cTOT as a noninvasive modality that may enhance healing by improving tissue oxygenation and microcirculation, although larger studies are needed given the small sample size, retrospective design, lack of a control group and single-center setting which restrict generalizability and prevent definitive conclusions regarding efficacy.

Gong (2025) presented a network meta-analysis of 67 randomized controlled trials (n=5957) that evaluated multiple non-pharmacological interventions for diabetic foot ulcers, including CDO. CDO was associated with a significant improvement in healing rate compared to standard care (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.40-4.58) and ranked moderately for reducing healing time (surface under cumulative ranking curves [SUCRA] 60.2%), though it was not among the top-performing modalities for wound closure or size reduction. Notably, CDO demonstrated the most favorable safety profile, with significantly fewer adverse events compared to standard care (OR, 0.27; 95% CI, 0.08-0.85; SUCRA 89.2%). However, limitations include substantial heterogeneity across studies (for example, variation in wound severity, treatment protocols, and outcome definitions), generally low to very low certainty of evidence for many comparisons, potential publication bias for some outcomes, and limited data for key endpoints such as recurrence and amputation, which restricts the strength and generalizability of conclusions regarding CDO’s comparative effectiveness.

A single-center randomized controlled trial (n=88) evaluated portable cTOT compared to moist wound therapy for chronic wounds over 28 days with follow-up to 12 weeks (Zhu, 2026). The CDO group demonstrated significantly greater early improvements, including higher healing rates at day 28 (45.5% vs. 11.4%, p<0.001), greater wound area reduction (88.8% vs. 73.3%, p<0.001), greater depth reduction (81.0% vs. 66.6%, p=0.018), and faster overall healing time (reduced by 13.5 days; 95% CI, 6.74-15.40; p=0.004), with no treatment-related adverse events. However, by 12 weeks, overall healing rates were similar between groups (95.5% vs. 90.9%, p=0.536), suggesting that the primary benefit of CDO is acceleration rather than increased ultimate healing. Limitations include a single-center design, small sample size, heterogeneous wound types with relatively few diabetic foot or venous ulcers, short follow-up duration, and limited ability to perform subgroup or multivariate analyses, which may restrict generalizability. Overall, the findings suggest that portable CDO may accelerate early wound healing but do not clearly demonstrate superiority in long-term outcomes.

According to Bowers (2020), “a chronic wound is one that fails to progress through a normal, orderly, and timely sequence of repair, or in which the repair process fails to restore anatomic and functional integrity after three months.” Established standards of care exist for chronic and non-healing wounds, with first-line treatments typically including debridement, topical antimicrobials, systemic antibiotics, moisture-retentive dressings, negative pressure wound therapy, and skin grafts or substitutes.

Topical continuous oxygen therapy devices (such as the EO₂ and the OxyGeni System) are wound care systems designed to promote healing by delivering oxygen directly to chronic, non-healing wounds through integrated dressings, tubing, and a portable oxygen supply. The oxygen is provided at normal atmospheric pressure and is not hyperbaric therapy. The system also helps to keep the wound from drying out. In August 2009, the U.S. Food and Drug Administration (FDA) gave 510(k) premarket approval to the TransCu O₂ System as a topical oxygen chamber for extremities. It was indicated for use with wound dressings to treat pressure ulcers, infected residual limbs, skin grafts, bums, frostbite and skin ulcerations due to diabetes, venous stasis, post-surgical infections and gangrenous lesions. Rebranding occurred in 2020 with a name change to EO₂ and OxyGeni. Trials and studies have been small, biased or did not show that topical continuous oxygen therapy devices were more effective than normal standards of care.

Atmospheric pressure: The force exerted by the weight of air in the Earth’s atmosphere on a surface. At sea level, standard atmospheric pressure is approximately 1 atmosphere (atm) or 760 mmHg.

Continuous diffusion of oxygen: A form of topical oxygen therapy that delivers a continuous, low-flow stream of oxygen directly to a wound surface, typically through a small portable device, to support healing by improving local oxygen availability.

Hyperbaric therapy: A medical treatment in which an individual breathes 100% oxygen in a pressurized chamber (greater than atmospheric pressure, usually 2-3 atm), increasing oxygen delivery to tissues via the bloodstream to promote healing and fight infection.

Topical: Refers to a treatment that is applied directly to a specific area of the body, such as the skin or a wound, rather than being taken orally or delivered systemically.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
For the following procedure code, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Peer Reviewed Publications:

1. Bowers, S, Franco, E. Chronic wounds: evaluation and management. Am Fam Physician. 2020; 101(3):159-166.
2. Du X, Zhang X, Liu J, Wang Z. Effects of oxygen therapy on patients with a chronic wound: a systematic review and meta-analysis. Adv Skin Wound Care. 2024; 37(5):1-9.
3. Frykberg RG. Topical wound oxygen therapy in the treatment of chronic diabetic foot ulcers. Medicina (Kaunas). 2021; 57(9):917.
4. Gong J, Sun X, Fu H, et al. Comparative efficacy and safety of non-pharmacological nursing interventions for diabetic foot ulcers: a systematic review and network meta-analysis. BMC Nurs. 2025; 24(1):1445.
5. Kormylo E, Cole W, Wielgomas J. Use of continuous topical oxygen therapy to treat lower-extremity surgical wound dehiscence: a retrospective review. Eplasty. 2025; 25:e23.
6. Mercurio M, Lavery LA, Agarwal A, Oropallo A. Cost-effectiveness of continuously diffused oxygen therapy compared with negative-pressure wound therapy. J Health Econ Outcomes Res. 2026; 13(1):30-38.
7. Niederauer MQ, Michalek JE, Armstrong DG. A prospective, randomized, double-blind multicenter study comparing continuous diffusion of oxygen therapy to sham therapy in the treatment of diabetic foot ulcers. J Diabetes Sci Technol. 2017; 11(5):883-891.
8. Niederauer MQ, Michalek JE, Liu Q, et al. Continuous diffusion of oxygen improves diabetic foot ulcer healing when compared with a placebo control: a randomised, double-blind, multicentre study. J Wound Care. 2018; 27(Sup9):S30-S45.
9. Oropallo AR, Serena TE, Armstrong DG, Niederauer MQ. Molecular biomarkers of oxygen therapy in patients with diabetic foot ulcers. Biomolecules. 2021; 11(7):925.
10. Zhu Y, Jiang Q, Zhan Y, et al. Clinical efficacy and safety of portable continuous topical oxygen Therapy for chronic wound management: a randomised controlled trial. Int Wound J. 2026; 23(2):e70837.
11. Zulbaran-Rojas A, Bara RO, Lee M, et al. Optimizing tissue oxygenation in reduction mammoplasty: the role of continuous diffusion of oxygen: a feasibility pilot randomized controlled trial. J Surg Res. 2023; 292:113-122.
12. Zulbaran-Rojas A, Mishra R, Pham A, Suliburk J, Najafi B. Continuous diffusion of oxygen adjunct therapy to improve scar reduction after cervicotomy - a proof of concept randomized controlled trial. J Surg Res. 2021; 268:585-594.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Federman DG, Dardik A, Shapshak D, et al. Wound Healing Society 2023 update on guidelines for arterial ulcers. Wound Repair Regen. 2024; 32(5):619-629.
2. Gould LJ, Alderden J, Aslam R, et al. WHS guidelines for the treatment of pressure ulcers-2023 update. Wound Repair Regen. 2024; 32(1):6-33.
3. Kirsner RS. The Wound Healing Society chronic wound ulcer healing guidelines update of the 2006 guidelines--blending old with new. Wound Repair Regen. 2016; 24(1):110-111.
4. Lavery LA, Suludere MA, Attinger CE, et al. WHS (Wound Healing Society) guidelines update: diabetic foot ulcer treatment guidelines. Wound Repair Regen. 2024; 32(1):34-46.
5. Marston W, Tang J, Kirsner RS, Ennis W. Wound Healing Society 2015 update on guidelines for venous ulcers. Wound Repair Regen. 2016; 24(1):136-144.

1. National Library of Medicine. Chronic wounds: Learn More - What are the treatment options for chronic wounds? Last update: October 1, 2025. Available at: https://www.ncbi.nlm.nih.gov/books/NBK326436/#:~:text=At%20first%2C%20chronic%20wounds%20are,or%20skin%20grafts%20are%20used. Accessed on August 13, 2026.

EO2 System (formerly TransCu O₂)
OxyGeni System with OxySpur dressing

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

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