Low-level light therapy (LLLT; ≤0.5 Watts; W) has advanced to the stage of guideline recommended treatment with payer coverage for treating shallow tissue oral mucositis. However, LLLT often fails in trials treating deeper tissue pathologies due to an inability to penetrate and deliver sufficient therapeutic light. By contrast, Class IV high-intensity laser therapy (HILT; 0.5-80W) typically at 100-fold higher powers has proven successful for treating these same deeper tissue pathologies. To evaluate the range of indications responding favorably to Class IV HILT, we searched PubMed, Google Scholar, and Cochrane databases from 2018 to March 2024 using the keywords "laser" AND "photobiomodulation" OR "therapy" AND "high" AND "patients" NOT "surgical", focusing on controlled trials. Effect sizes were determined using Cohen’s d. Fifty-six identified studies (n=1,486 HILT vs n=1,494 controls) reported zero serious adverse events. HILT reduced pain in 100% of the trials focused on the knee (n=10), spine, shoulder/arm, and wounds with large effect sizes (>90%). Positive outcomes were demonstrated for the hand/wrist (n=5), feet, face/jaw, bone osteoporosis, and endometriosis. Improvements in range of motion (94%; n=16), functional outcomes (84%; n=37), quality of life (80%; n=20), knee cartilage thickness, rotator cuff tear size, and nerve conduction were demonstrated. Larger effect sizes occurred in follow-up measurements made after cessation of treatment (n=18) indicating that benefits were sustained and not merely transient. The average (median, range) power used was 9.5W (10.5, 0.5-30) and the average power density was 9.1W/cm2 (8; 1-30). We conclude that Class IV HILT is an exceptionally safe, effective, and increasingly recognized treatment that is in a promising discovery phase of research for an expanding list of indications with deep-tissue pathologies. The medical and payer communities should include HILT as a viable treatment option for indications showing positive outcomes in the published research.
