Evaluation of Lymphatic Response to Physiotherapy in Patients With Swelling Associated With Superficial Venous Disease

• Indocyanine Green near infrared fluorescence imaging (Combination product), also known as near-infrared fluorescence lymphatic imaging: A total of 10 intradermal injections of 25 ug indocyanine green (ICG) in 0.1 mL saline are administered in the feet, medial ankles, lateral calves, and thigh. The total dose of ICG will not exceed 250 ug. After injection, the legs will be illuminated by the dim output of a 780 nm laser diode, and the resultant fluorescent signal emanating from ICG-laden lymph will be collected by a custom built near-infrared fluorescent lymphatic imager.
• advanced pneumatic compression (Device): The advanced pneumatic compression device (APCD) mimics manual lymphatic drainage, a light massage that stimulates lymphatic uptake and function and frequently prescribed for lymphedema therapy. Daily treatment will be prescribed for approximately 30 days.
• Duplex ultrasound (Diagnostic test): Duplex ultrasound to measure venous reflux will be done at each visit.
• compression wrap (Device): A compression wrap, to provide 20-40 mm Hg of pressure, will be provided for daily use between visits (approximately 30 days).

Primary outcomes

• Extent of Dermal Backflow [Assessed at Visit 1 and 2 (approximately 30 days apart)]: The area of abnormal dermal lymphatic backflow in the leg.
• Lymphatic pumping rate [Assessed at Visit 1 and Visit 2 (approximately 30 days apart)]: Number of pumping events observed per minute assessed in the medial ankle.

Secondary outcomes

• Correlation of CEAP score and lymphatic pumping rates [Assessed at Visit 1 and 2 (approximately 30 days apart)]
• Correlation of CEAP score with extent of dermal backflow [Assessed at Visit 1 and 2 (approximately 30 days apart)]
• Change in limb volume between arms. [Assessed at Visit 1 and 2 (approximately 30 days apart)]: Limb volume, determined from limb circumference measurements, will be assessed at both visits.
• Change in LLIS score between arms [Assessed at Visit 1 and 2 (approximately 30 days apart)]: Patient reported outcomes assessed using the Lymphedema Life Impact Scale (LLIS) at each visit and change determined after Visit 2. Possible scores range from 0 to 100 with a higher score indicating a greater impact of disease on quality of life.
• Change in Venous Clinical Severity Score (VCSS) between arms [Assessed at Visit 1 and 2 (approximately 30 days apart)]: Venous Clinical Severity Score (VCSS) will be assessed at each visit. Possible scores range from 0 to 30 with a higher score indicating a greater severity of vascular disease.
• Change in patient reported outcomes between arms [Assessed at Visit 1 and 2 (approximately 30 days apart)]: Patient reported outcomes assessed using the Lower Extremity Functional Scale (LEFS) at each visit and change determined after Visit 2. Possible scores range from 0 to 80 with a higher score indicating a greater impact of disease on limb functionality.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Participant >18 years of age
2. Participant with an objective diagnosis of CEAP Class 3 or 4 superficial venous disease (superficial reflux time >0.5 sec), with venous edema (revised VCSS score of 2 or 3 for edema).
3. Participant must provide informed consent
4. Participant is willing and able to fulfill study timeline
5. Participant is a candidate for APCD treatment per the FTP indications
6. Lymphatic dysfunction is observed, using NIRF-LI, in affected limb.

Exclusion Criteria:

1. History of pelvic or lower extremity cancers
2. Systemic organ failure including heart failure
3. BMI >35
4. Previous endovascular or open vascular interventions
5. Patients with known, or family history of, primary lymphedema
6. Prior use of advanced pneumatic compression device, or complete decongestive therapy (CDT) on the lower extremities
7. Peripheral arterial disease with ABI <0.8
8. Participants with deep venous obstruction
9. Skin disease not related to CVD
10. Participants with iodine allergies including patients with shellfish allergy who may be allergic to iodine that may be in the ICG formulation
11. Females who are pregnant or breastfeeding
12. Females with the intent of becoming pregnant within 30 days after participation in final imaging session

• John C Rasmussen, PhD, Principal investigator, The University of Texas Health Science Center, Houston