Indocyanine Green-Guided Lymphatic Sparing Surgery for Lipedema: A Case Series

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Minimal excision and minimal improvement

Photos could be more consistent

Timiing of tumescent and ICG injection and epi effect

Limitation of ICG SPY/PHI

Author Response

Reviewer 1

Comment 1: Minimal excision and minimal improvement

Response 1: Thank you for this comment. We have expanded our description of our protocol and goals. Because liposuction was intentionally focal, aspirate volumes are not directly comparable to circumferential liposuction series; procedural intent, anatomic coverage, and safety endpoints differ. In addition, we prefer not to perform radical excision. We targeted selected excision to symptomatic areas in patients with large overhanging lobules. We have included data including specimen weight and size as well. We clarified the lymphatic-sparing strategy and expanded quantitative outcomes. The new Results report average aspirate volume and resection weights, and add functional improvements (LLIS reduction; improved walking) to show meaningful effect sizes. We also explain that excision was targeted to symptomatic lobules to preserve lymphatics.

Comment 2: Photos could be more consistent

Response 2: Thank you, we agree and have updated all the figures included. Figure captions have been standardized to pre- vs postoperative views at specified follow-up intervals (6 or 12 months) and consistent anterior/posterior positions.

Comment 3: Timing of tumescent vs ICG and possible epinephrine effect

Response 3: The Methods now state the exact sequence in combined cases (tumescent liposuction performed before ICG lymphography), the ICG concentration and injection volumes, and the imaging protocol. This clarifies potential vasoactive effects and our rationale for the workflow.

Comment 4: Limitations of ICG SPY/PHI

Response 4: The Limitations section is expanded to note depth limitations (inability to visualize deeper channels), equipment availability, and that 83% of extremities did not show proximal channels due to adipose depth.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript presents a valuable case series on the application of ICG lymphography in lymphatic-sparing surgery for lipedema. The topic is clinically relevant and the study is generally well-structured. However, several issues should be addressed to improve the clarity, methodological rigor, and overall academic impact:

(1) The abstract does not clearly state the main conclusions. It should explicitly highlight the clinical value of ICG in preserving lymphatic vessels during surgery.

(2) The Methods section describes lipedema Types I–V, yet Type IV is missing from the Results (Table 1).

(3) The description of the lymphatic-sparing technique is too brief. More procedural details should be provided (e.g., the excitation wavelength of ICG and the near-infrared imaging system used), or a supplementary figure should be included if available.

(4) The study lacks quantitative comparisons between preoperative and postoperative images. Images alone are insufficient; each case should be supplemented with measurement data, ideally summarized in bar charts, to more effectively demonstrate the outcomes.

(5) Some units are not formatted correctly (e.g., line 112: “2.5 mg/cc”; line 124: “1 mg/1 L”). Please carefully review and revise.

(6) References 3 and 6 are duplicates (Clin Obes. 2023 Jun;13(3): e12588). Please verify and remove the duplicate entry.

 

Author Response

Reviewer 2

Comment 1: The abstract does not clearly state the main conclusions. It should explicitly highlight the clinical value of ICG in preserving lymphatic vessels during surgery.

Response 1: We apologize for this lack of clarity. We agree and have updated the abstract, which now explicitly states that ICG guidance reliably visualizes lymphatics intraoperatively, enabling safe debulking while preserving lymphatic function.

Comment 2: The Methods section describes lipedema Types I–V, yet Type IV is missing from the Results (Table 1).

Response 2: We agree, and have expanded our cohort to include two additional patients, one of which was diagnosed with Type IV lipedema. Type IV has also been added to the Results table, aligning with the Methods and included cohort.

Comment 3: The description of the lymphatic-sparing technique is too brief. More procedural details should be provided (e.g., the excitation wavelength of ICG and the near-infrared imaging system used), or a supplementary figure should be included if available.

Response 3: Thank you for this comment. We agree and have expanded the methods to specify ICG preparation (25 mg/vial resuspended to 2.5 mg/mL), intradermal injection sites/volumes (0.1 mL), and near-infrared parameters (illumination 750–800 nm; emission peak ~832 nm; long-pass filter <820 nm) with the SPY-PHI handheld system.

Comment 4: The study lacks quantitative comparisons between preoperative and postoperative images. Images alone are insufficient; each case should be supplemented with measurement data, ideally summarized in bar charts, to more effectively demonstrate the outcomes.

Response 4: Thank you for this comment. Although we have not included pre-and-post operative changes in measurement data, we have included data on average specimen weight and size that was removed from each limb. We have also added quantitative endpoints: LLIS improvement at 12 months.

Comment 5: Some units are not formatted correctly (e.g., line 112: “2.5 mg/cc”; line 124: “1 mg/1 L”). Please carefully review and revise.

Response 5: Thank you for noticing this mistake. We have updated all units (e.g., mg/mL; 1:1,000 epinephrine per liter; 0.1 mL injections).

Comment 6: References 3 and 6 are duplicates (Clin Obes. 2023 Jun;13(3): e12588). Please verify and remove the duplicate entry.

Response 6: We again apologize for this oversight. Reference list has been updated, with duplicates removed.

Reviewer 3 Report

Comments and Suggestions for Authors

Thank you for sharing your experience with ICG lymphography with liposuction/excision. How much extra time would the use of the ICG/SPY add to the procedure? Have you tried the use of ink such as Patent Blue that is used in Sentinel lymph node biopsies where the blue dye filled lymphatics can be visualise to the bare eye? My understanding that the classic Lipedema is usually in women. The fact that half of your cohorts are men would their diagnosis be morbid obesity instead? I note that reference 3 and 6 are duplicates.

Author Response

Reviewer 3

Comment 1: How much extra time would the use of the ICG/SPY add to the procedure?

 

Response 1: Thank you very much for pointing this out. We have modified the manuscript to include not only total operative time, but also the additional time for ICG lymphography. Approximately 15 minutes were added to operative time by ICG/SPY.

Comment 2: Have you tried the use of ink such as Patent Blue that is used in Sentinel lymph node biopsies where the blue dye filled lymphatics can be visualise to the bare eye?

 

Response 2: This is a great question. We have included a discussion of blue dyes (e.g., patent blue) used in cadaveric studies and explain they offer only line-of-sight visualization after dissection and no transcutaneous imaging; ICG provides real-time mapping through intact skin/fat.

Comment 3: My understanding that the classic Lipedema is usually in women. The fact that half of your cohorts are men would their diagnosis be morbid obesity instead?

 

Response 3: Thank you, as this is a common misconception that lipedema only affects women. Although lipedema is found to have a hormonal component, men can also be affected.

Comment 4: I note that reference 3 and 6 are duplicates.

 

Response 4: We apologize for this oversight. Duplicates were removed; the bibliography has been corrected.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have solved my concerns. 

Author Response

Thank you for your time and thoughtful comments.

Reviewer 3 Report

Comments and Suggestions for Authors

Please reference the comment that man can have lipedema

It would appear that lipedema classically are women of the 'germanic' group with family history. How do you differentiate or diagnose lipedema in your patients?

The original abstract and 'limitation' section have n=6 and the main paper is n=8. Please clarify

It would seem that dyes such as patent blue give the surgeon gross visual demonstration of the lymphatics rather than having to turn the light off to 'visualise' lymphatics that have to be marked would make the operation longer than necessary. What is the argument for ICG instead of patent blue?

Author Response

Comment 1: Please reference the comment that man can have lipedema.

Response 1: Thank you for your comment, we have included in the introduction, in the second paragraph, that men can be affected by this disease as well.

Comment 1: How do you differentiate or diagnose lipedema in your patients?

Response 2: Thank you for this important comment. We agree. The diagnosis of lipedema is made clinically, and we have included our diagnostic criteria in the Methods section. We have also included how we distinguished patients with lipedema from those with lymphedema, as they can often overlap.

Comment 3: The original abstract and 'limitation' section have n=6 and the main paper is n=8. Please clarify

Response 3: We apologize for this oversight; we have corrected the abstract and limitation sections to reflect the total sample size of 8 patients.

Comment 4: It would seem that dyes such as patent blue give the surgeon gross visual demonstration of the lymphatics rather than having to turn the light off to 'visualise' lymphatics that have to be marked would make the operation longer than necessary. What is the argument for ICG instead of patent blue?

Response 4: Thank you for this thoughtful question. Patent blue (PB) allows visualization of exposed superficial lymphatics during dissection; however, its utility is largely confined to intraoperative identification after tissue exposure and it does not provide functional assessment or pre-incision mapping that would assist with staging or strategic planning in lipedema. By contrast, indocyanine green (ICG) near-infrared fluorescence enables real-time, transcutaneous visualization of lymphatic flow across broader limb territories, yielding dynamic visualization of lymphatic patterns as they track through a limb distally to proximal that is directly relevant to operative decision-making. NIR emission from ICG penetrates several millimeters to ~1–2 cm, allowing transcutaneous tracking of lymphatics of an entire limb that are not visible to the naked eye. We acknowledge, as our data show, that ICG penetration is attenuated by thick adiposity and that lymphatic patterns were not visualized in 83% of extremities in our series; limiting ICG utility in staging patients with high adiposity. Nonetheless, in the subset with appreciable fluorescence, ICG provided actionable, pre-dissection information that informed incision placement and intraoperative assistance to avoid injury to functioning collectors—capabilities that PB cannot offer prior to exposure. For these reasons, despite its limitations in lipedema, ICG was selected as the more informative modality for the aims of this study.