TABLE 2.

Characteristics of included studies.

Studies	Inclusion criteria of KOA	High-intensity laser therapy			Control		Analyzable outcomes
		Participants	Treatments	HIL device	Participants	Treatments
Akaltun et al. (30)	(1) Grade II-III KOA cases according to K-L classification; (2) being aged between 45 and 75; (3) having knee pain for at least 6 months; and (4) the VAS score being at least 3 or more.	n = 20 age (year): 57.85 ± 8.07 gender (M/F): 6/14 BMI (Kg/m2): 29.94 ± 5.49	The analgesic mode was applied on the first 3 days. A total of 300 J was applied as 12 J/m2 25 cm2 at a frequency of 25 Hz in these sessions. The biostimulation mode was implemented as of the fourth session. A total of 3,000 J was applied as 120 J/cm2 in this mode. The application was made continuously with circular motions in both modes. (A total of 10 sessions were implemented)	Nd:YAG Laser with 1,064 nm wavelength (BTL-6000 HIL 12 W)	n = 20 age (year): 58.62 ± 11.28 gender (M/F): 6/14 BMI (Kg/m2): 31.95 ± 4.87	Placebo laser: The same device was applied in the form of a sham laser that did not radiate laser beam. Exercise: The home exercise program included ROM exercises, stretching, strengthening, and flexibility exercises.	Null
Alayat et al. (31)	(1) Degenerative osteoarthritic knee of grade III or less based on K-L classification; (2) persistent pain ≥ 4 on the VAS for more than 3 months in one or both knees; (3) BMI ≤ 30 kg/m2; and (4) self-reported disability due to knee pain with a score of at least 25 on the WOMAC.	n = 23 age (year): 55 ± 4.41 gender (M/F): all male height (cm): 171.9 ± 3.46 weight (kg): 83.21 ± 5.82 BMI (Kg/m2): 28.15 ± 1.72	Each anterior or posterior knee surface was scanned in two sub-phases (initial and final) with three fluency levels. Initially, fast scanning was performed with gradually increasing fluency in three levels: level I: with energy density of 1,430 mJ/cm2, frequency of 30 Hz, in 30.4 s; level II: with energy density of 1,530 mJ/cm2, frequency of 25 Hz in 34 s; and level III: with energy density of 1,780 mJ/cm2, frequency of 20 Hz, and time of application 36.6 s. In each level, 250 J was delivered with a total of 750 J for anterior knee surface, and the same sequence was performed to posterior knee surface. The final phase was similar to the initial phase except that the scanning was slow. The average area was 200 cm2 and the average energy density was 15 J/cm2, with a total energy of 3,000 J delivered in each session. (2 times per week for 6 weeks)	Pulsed Nd:YAG laser (HIRO 3.0, ASA, Arcugnano, Vicenza, Italy)	n = 22 age (year): 52.86 ± 5.03 gender (M/F): all male height (cm): 170.95 ± 4.64 weight (kg): 83.68 ± 4.50 BMI (Kg/m2): 28.63 ± 1.00	Placebo laser: A sham laser was administered in the same way as the active laser. Exercise: The program included ROM exercise, flexibility, stretching, and strengthening training.	VAS WOMAC (pain, stiffness, function)
					n = 22 age (year): 53.64 ± 3.54 gender (M/F): all male height (cm): 171.64 ± 3.82 weight (kg): 85.18 ± 3.42 BMI (Kg/m2): 28.91 ± 0.49	Medication: patients received glucosamine sulfate potassium chloride and chondroitin sulfate sodium 3 times daily.
Angelova and Ilieva (32)	(1) Duration of the symptoms for over 4 years and X-ray stages II and III by K-L; (2) without local application of corticosteroids or hyaluronic acid during the last 6 months; (3) without physiotherapy during the last 6 months; and (4) being treated with physiotherapy or drugs more than 6 months before.	n = 35 age (year): 65.11 ± 1.4 gender (M/F): 11/24	The first three procedures are with analgesic effect with dose 12 J/cm2 = 300 J for treated area of 25 cm2. Laser therapy is applied on the medial and lateral sides of the knee, distant application, for 2 min, 25 Hz frequency. The next 4 sessions use biostimulating parameters, applied with dose 120 J/cm2 = 3,000 J treated area 25 cm2, applied on the medial side of the knee, 10 min. (A total of seven sessions were implemented)	Semiconductive neodymium laser IV with wave length 1,064 nm and maximal power 12 W (BTL)	n = 37 age (year): 64.71 ± 1.98 gender (M/F): 12/25	Placebo laser: The patients are treated with imitation of laser treatment by directing the laser device without turning on the light beam (sham laser).	VAS
Delkhosh et al. (33)	The condition of patients with KOA was based on a diagnosis of specialists or doctors from Orthopedics for Physiotherapy Centers of the University of Medical Sciences.	n = 15 age (year): 43.5 ± 8.4 gender (M/F): all female height (cm): 154.1 ± 5.5 weight (kg): 58.5 ± 4.8	The Ga-A1-As laser with maximal power of 5 W and wave length of 1,064 nm were used on 4 points (anterior and inside of the knee joint). Each session was divided into three phases, and each phase was 4 min. The total energy was approximately 1,400 J per session.	Ga-A1-As laser	n = 15 age (year): 48.3 ± 4.0 gender (M/F): all female height (cm): 150.5 ± 4.4 weight (kg): 70.5 ± 1.0	Placebo laser: The patients received inactive laser (the device was turned off).	VAS WOMAC (total)
					n = 15 age (year): 44.5 ± 8.7 gender (M/F): all female height (cm): 150.3 ± 4.5 weight (kg): 58.3 ± 1.0	Low level laser therapy: The laser Ga-Al-As with power of 300 mW and wave length of 830 nm were used on 4 points (anterior and inside of the knee joint). Dosage: average energy density was 50 J/cm2 per point.
Gworys et al. (34)	The study involved patients with pain of more than 6 weeks’ duration and a diagnosis of KOA according to the criteria established by the American College of Rheumatology. Enrollment criteria also included 2nd degree joint injury according to Seyfried on the basis of clinical examination, no intraarticular corticosteroids, hyaluronic acid or other drugs within the 3 months preceding the study, no physical therapy during the 3 months, and no contraindications for physical therapy.	n = 30 age (year): 65.4 ± 9.6	The patients received two-wave laser irradiation (power 1,100 mW, frequency 2,000 Hz, dose 12.4 J/point, energy density 6.21 J/cm2). The knee joint was irradiated in 12 points: three points each at the level of the medial and lateral aspect of the knee joint gap, two points each at the level of the patellofemoral joint on the superior and inferior aspect of the joint, and two points in the popliteal fossa. Laser therapy sessions were performed once a day, 5 days a week over 2 weeks. Each patient attended 10 sessions.	Multiwave Locked System (MLS) Therapy (synchronized generation of continuous (wave length 808 nm) and pulsed (wave length 905 nm) laser light)	n = 31 age (year): 67.7 ± 11.3	Placebo laser: Laser therapy procedures were simulated without actual irradiation.	VAS
					n = 34 age (year): 57.6 ± 11.8	Low level laser therapy: The patients received one-wave laser irradiation (wave length 810 nm, dose 8 J/point, surface density of energy 12.7 J/cm2, power 400 mW, and surface density of power 634.9 mW/cm2) in the continuous mode.
					n = 30 age (year): 65.9 ± 9	Mild dose laser therapy: The patients received two-wave laser irradiation (power 1,100 mW, frequency 2,000 Hz, dose 6.6 J/point, energy density 3.28 J/cm2).
Kheshie et al. (35)	(1) Had painful KOA for at least 6 months with degenerative osteoarthritic knee of grade II-III or less based on radiographic diagnosis in the K-L grading of osteoarthritis; (2) had no limitation of range of motion except for minimum tightness in the knee joint; (3) did not engage in any high-joint-loading exercises such as hiking or tennis playing and had not undergone any specific treatments 3 months before entering the study; (4) had a minimum score of 25 on the WOMAC total score, and (5) had a knee pain ≥ 4 on the VAS in the previous 3 months.	n = 20 age (year): 52.1 ± 6.47 gender (M/F): all male height (cm): 172 ± 5.49 weight (kg): 88.55 ± 7.51 BMI (Kg/m2): 29.94 ± 3.36	The scanning was performed transversely and longitudinally in the anterior, medial, and lateral aspects of the knee joint with emphasis on the application on the joint line between the tibial and femoral epicondyles. The total energy delivered to the patient during one session was 1,250 J through three phases of treatment. The initial phase was performed with fast manual scanning with a total of 500 J. In the initial phase, the laser fluency was set to two successive sub-phases of 710 and 810 mJ/cm2 for a total of 500 J. In the intermediate phase, the handpiece was applied on the joint line just proximal to the medial and lateral tibial condyles with 25 J, a fluency of 610 mJ/cm2, and a time of 14 s for each point and a total of 250 J in this phase. The final phase was the same as the initial phase except that scanning was slow manual scanning. The application time for all three phases was approximately 15 min with the total energy delivered to the patient during one session of 1,250 J. (two sessions per week for 6 weeks)	Pulsed Nd:YAG laser (HIRO 3.0, ASA, Arcugnano, Vicenza, Italy)	n = 15 age (year): 55.6 ± 11.02 gender (M/F): all male height (cm): 175 ± 6.30 weight (kg): 87.00 ± 7.75 BMI (Kg/m2): 28.51 ± 3.35	Placebo laser: Patients attended the physical therapy clinic two times a week for 6 weeks and received sham laser. Exercise: Patients received an exercise program which consisted of active ROM exercises, muscle strengthening, and flexibility exercises.	VAS WOMAC (pain, stiffness, function)
					n = 18 age (year): 56.56 ± 7.86 gender (M/F): all male height (cm): 173 ± 4.92 weight (kg): 85.16 ± 14.03 BMI (Kg/m2): 28.62 ± 5.20	Low level laser therapy: Patients received gallium-arsenide diode (GaAs) laser (BTL-5000 laser) infrared probes with a wavelength of 830 nm, output power of 800 mW, average energy density of 50 J/cm2, frequency of 1 KHz, and duty cycle of 80%. The cluster laser was in direct contact and perpendicular to the affected knee with a time of application of 32 min and 33 s per session and a total energy of 1,250 J. (two sessions per week for 6 weeks)
Kim et al. (36)	The subjects’ attending doctors had diagnosed them with KOA based on clinical findings and images taken using X-ray equipment.	n = 10 age (year): 65.3 ± 4.2 height (cm): 159.3 ± 7.4 weight (kg): 62.0 ± 11.0	A high intensity laser was applied in the tibia and femoral epicondyle for 5 min. A separation distance of around 1 cm between the handpiece and the skin was also maintained throughout the treatment. The intensity of the HIL was level 2, the frequency was 11 Hz, and the total amount of delivered energy was 1,500 mJ/cm2. (3 times per week for 4 weeks)	HEALTRON (United Technology Inc., Israel)	n = 10 age (year): 65.5 ± 4.0 Height (cm): 159.9 ± 8.2 weight (kg): 61.6 ± 10.4	Thermotherapy plus interferential current: The program consisted of hot pack treatment for 20 min, interferential current therapy for 15 min, and deep heat diathermy using ultrasonic waves for 5 min.	VAS WOMAC (total)
Kim et al. (37)	The subjects had grade II osteoarthritis of Kellgren classification and knee pain.	n = 14 age (year): 60.6 ± 2.98	Patients underwent treatment 30 times. Three sub-phases of high intensity laser, 500 J of the energies were evenly transferred through each phase 60 s. (A) For the anterior condyle of the femur, the internal and external hematoma of the knee flexed at 90° on supine position. (B) For the posterior side of the patella, the lateral and medial windows at the 30° knee flexion state. (C) For the posterior condyle of the femur, the internal and external hematoma of the knee over the popliteal fossa at the maximum knee extension state. (5 times per week for 6 weeks)	Pulsed Nd:YAG laser (HIRO 3.0, ASA, Arcugnano, Vicenza, Italy)	n = 14 age (year): 61.6 ± 2.98	Placebo laser: The same device was applied in the form of a sham laser that did not radiate laser beam.	VAS WOMAC (pain, stiffness, function)
Mostafa et al. (38)	Patients were diagnosed with chronic KOA according to the American College of Rheumatology criteria, and they had stage II KOA measured by X-ray, according to Kellgren and Lawrence.	n = 20 age (year): 46.62 ± 8.68 height (cm): 163.2 ± 7.3 weight (kg): 77.17 ± 6.38 BMI (Kg/m2): 29.26 ± 2.48	Participants received high-intensity pulsed Nd:YAG laser therapy at a frequency of 30 Hz and total delivered energy of 1,500 mJ/cm2 in each session, three sessions/week for 4 weeks. To expose the joint surfaces to the laser beam, the HILT handpiece was positioned in contact with and perpendicular to the medial side of the knee while the patient lay supine with the knee flexed at 30° (optical windows). The HILT handpiece was then moved transversely and longitudinally in the anterior, medial, and lateral aspects of the knee joint, emphasizing the joint line between the tibial and femoral epicondyles.	Pulsed Nd:YAG laser (HIRO 3.0, ASA, Arcugnano, Vicenza, Italy)	n = 20 age (year): 40.12 ± 9.45 height (cm): 162.2 ± 7.1 weight (kg): 76.02 ± 10.23 BMI (Kg/m2): 28.82 ± 5.23	Shock wave therapy: Patients received 1,000 extracorporeal shock wave pulses (Evotron RFL0300 Focal Shockwave; manufactured by Swiss Tech Medical AG, Switzerland) with an intensity of 0.05 mJ/mm2, one session/week for 4 weeks. Shock wave therapy is applied to the tender point of the medial tibial plateau area in the affected knee while the patient is lying in a supine position with knees bent at 90°.	VAS WOMAC (total)
Nazari et al. (39)	(1) X-ray stages II and III osteoarthritis according to the criteria proposed by K-L; (2) age between 50 and 75 years; (3) BMI equal to or less than 30; (4) knee pain lasted at least 6 months with intensity at least 3 on VAS scale in activities such as going up- and downstairs, sitting and squatting; (5) no history of acute traumatic injuries; (6) no history of previous surgery or injury in the knee and lower extremities; (7) lack of neuromuscular disease; (8) normal mental state; (9) absence of bone implants; (10) no history of new fractures; (11) lack of cancerous tumors; (12) no history of chronic disease and any condition that affect the study; (13) not participating in sports programs and physical therapy in the recent 3 months; and (14) no history of knee intra-articular injection in the past 6 months.	n = 30 age (year): 61.5 ± 3.9 gender (M/F): 13/17 BMI (Kg/m2): 27.7 ± 1.4	The treatment was performed in a slow manual scanning in longitudinal and perpendicular direction on the medial and lateral sides of the knee with a 6-cm probe. The probe was placed vertically in contact with the joint line while the patient was in a supine position and the knee flexed at 30° for 8 min, at a frequency of 30 Hz with a peak power of 5 W, a duty cycle of 70%, energy density of 60 J/cm2, and total energy of 2,400 J during one session. (3 times per week for 4 weeks)	Pulsed mode of E20780–Nd:YAG laser with wavelength of 1,064 nm (Fysiomed, Belgium)	n = 30 age (year): 62.4 ± 3.14 gender (M/F): 14/16 BMI (Kg/m2): 27.2 ± 1.6	Electric stimulation plus ultrasound: The participants were treated by a special equipment, including transcutaneous electric nerve stimulation (TENS) and ultrasound (US) for 12 sessions, on alternate days. The former was delivered by two self-adhesive electrodes which were placed on the medial and lateral parts of the knee joint line, which was applied to the patients using a frequency of 100 Hz, pulse width of 50–100 μs, and quadratic biphasic symmetrical pulse shape for 20 min, and the intensity (mA) was set at the individual threshold of a tingling sensation. The latter protocol consisted of continuous ultrasonic waves of 1 MHz frequency and 1 W/cm2 intensity applied with a 5 cm diameter applicator. The patients were placed in a supine position, and the ultrasound was applied to the medial and lateral parts (5 min on each side) of the knee in circular movements with the probe at right angles to ensure maximum absorption of the energy.	VAS WOMAC (pain, stiffness, function, total)
					n = 30 age (year): 62.24 ± 3.87 gender (M/F): 14/16 BMI (Kg/m2): 27.5 ± 1.8	Exercise: The program consisted of nine exercises as follows: walking at the usual speed on a flat surface, hamstring and calf gentle stretches, straight leg raise, quadriceps setting, pillow squeeze, heel raise, one leg balance, step ups, and quadriceps strengthening.

KOA, knee osteoarthritis; HIL, high-intensity laser; K-L, Kellgren-Lawrence; ROM, range of motion; BMI, body mass index; Nd:YAG, Neodymium:Yttrium Aluminum Garnet; VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.