LLLT Effects on Inferior Alveolar Nerve (IAN) Recovery Post-orthognathic Surgery
Phase: NA
Conditions: Mandible; Deformity, Surgical Healing, Orthognathic Surgery, Nerve Injury
Sponsor: Albert Einstein College of Medicine

Title:  LLLT Effects on Inferior Alveolar Nerve (IAN) 
Recovery Post-orthognathic Surgery
NCT04910074
IRB#:  2021-12990
IRB Approval Date:  03/16/2022
IRB NUMBER: 2021-12990
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022
IRB APPROVAL DATE: 03/16/2022

1
Background and Significance
Orthognathic surgery is an essential part of correcting dentofacial deformities. The most common 
surgery for correcting mandibular deformities is the bilateral sagittal split osteotomy (BSSO). The BSSO 
was first developed in 1957 by Obwegeser(1), and allowed for anteroposterior correction of the 
mandible in either a Class II or Class III direction. The BSSO has been modified over time to improve 
surgical stability and reduce negative post-operative sequelae. Despite the modifications, there are still 
several potential complications that patients may experience. The most common post-operative 
complications are pain, swelling and nerve dysfunction. 
As with any surgery, pain and swelling are unavoidable, but the extent can be variable. A variety of both 
pharmaceutical and non-pharmaceutical approaches are generally used to improve pain and swelling, 
including warm compresses, pressure dressings and analgesics. Physical interventions may reduce 
swelling, which in turn reduces pain, but are limited in their penetration. Meanwhile medications carry 
their own potential negative consequences; opioids carry a risk for dependence and neutropina and 
non-steroidal anti-inflammatories can cause digestive issues, renal problems.
Nerve dysfunction leading to neurosensory deficits are a relatively common side effect of a BSSO, with 
literature estimating rates between 9% to 84.6% (2, 3) The inferior alveolar nerve (IAN) runs through the 
mandibular canal in the body of the mandible, with a branch, the mental nerve, splitting off and exiting 
the bone at the mental foramen between the first and second premolars. The IAN provides sensation to 
the gingiva and teeth, while the mental nerve provides sensation to the lips and the chin. During the 
BSSO, the IAN is necessarily moved and is at risk for either direct or indirect injury, which leads to the 
neurosensory deficits which are usually transient, but can be permanent in some cases (4-7). Therapy 
for IAN dysfunction is limited.
One treatment modality that has solid evidence to treat both sensory nerve dysfunction and pain is low-
level laser therapy (LLLT). LLLT has been established as viable therapy that modulates the body’s own 
healing potential in recovery from injury and surgery. The proposed mechanism of LLLT is that low 
intensity laser light applied to body tissues penetrates and scatters into the tissue, and the scattered 
energy stimulates a cascade reaction that leads to upregulating of healing and a reduction of 
inflammation (8).
Existing studies have shown that LLLT can modulate the post-surgical healing and pain (9, 10) and nerve 
recovery in orthognathic surgery patients (11-15,). Two systematic reviews have also determined that 
LLLT is an efficacious therapy to reduce pain and have significant long-term improvement neurosensory 
deficits over placebo (16, 17). Additionally, the literature has a consensus that the adverse effects of 
LLLT are virtually non-existent, with both review papers noting no negative complications reported in 
any of the papers included in the reviews. Both review papers, however, discuss that the existing 
literature has too few studies that are well-designed. Both review articles recommended more objective 
analysis of neurosensory function, as many relied on objective patient reports, and a longer follow-up 
period. Additionally, many studies have been conducted using a split-mouth design, in which one side 
receives LLLT and the other side doesn’t, in order to increase the sample size without increasing the 
number of patients. The issue is, according to the current understanding of LLLT (8, 9), the 
photobiomodulation effect can travel away from the site of LLLT administration. There are no 
documented adverse effects of LLLT.
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022

2
This study would aim to study the effects of LLLT on pain, swelling and neurosensory function on 
patients who have undergone orthognathic surgery with BSSO and compare the effects on a control 
group of patients undergoing similar surgery who will not receive any extraordinary post-op care.
Hypothesis
Administration of low-level laser therapy along the skin over the mandibular body of patients who have 
had bilateral sagittal split osteotomy surgery for correction of the position of the mandible will reduce 
pain and swelling and improve neurosensory dysfunction when compared to patients who do not 
receive the laser treatment.
Study Design
The study will have two groups into which patients will be assigned to a control group and an 
experimental group through a random number generator. Patients will undergo their planned surgical 
procedure and receive instructions as per standard clinic protocols, in both pre- and post-operative 
settings. The standard instructions include information on pain and swelling management. The patients 
will also receive post-operative medications, including an NSAID and an opioid for pain management and 
a steroid to reduce inflammation and swelling. The patients will be seen at one-week intervals for six 
weeks for post-operative follow-ups, as per standard clinic protocols. The experimental group will 
undergo low level laser therapy (LLLT) at weekly intervals. Subject treatment assignments will remain 
blinded until the final subject has completed follow up and all data has been recorded and validated.  
Urgent, immediate unblinding due to medical emergency may be authorized by the Investigator.  When 
possible, the treatment assignment will be provided to the treating physician in order to maintain the 
blind for the Investigator and study staff. All instances of subject unblinding will be documented in the 
study record.
The proposed LLLT protocol will use the Biolase Epic X, an InGaAsP diode laser (940nm) using the pain 
relief handpiece, a device which has received FDA approval (GUDID 00647529002537) for the treatment 
of pain, muscle relaxation and healing via increased local circulation. The LLLT will be administered to 
the experimental group at 30 j/cm2. The laser will be applied extraorally, on the skin overlying the 
mandible. Application will be for 40 seconds per side, with 10 seconds administered in four places along 
the jawline, 1 cm apart starting from the gonial angle. The timing would coincide with standard post-
operative care, with the first LLLT administration performed on post-operative day 1, prior to the 
patient’s discharge from the hospital. The follow-up LLLT doses would be given at the standard post-op 
follow-up visits, at one-week intervals, which would be at week 1, week 2, week 3, week 4, week 5, and 
week 6. Patients will be seen for evaluation at week 8 and again at approximately 20 weeks post-
surgery. The control group will follow the same post-op visit schedule, but receive a dummy treatment 
in which the laser handpiece is moved over the patient’s jaw in a similar fashion as the experimental but 
without laser irradiation.
Nerve function, pain and swelling will be measured according to objective measures. A baseline 
measurement will be recorded pre-operatively for nerve function and pain. Baseline for swelling will be 
used from the final measurement at week 8, due to the changes in mandible length caused by the 
orthognathic surgery. Measurements for each outcome will also be performed on the days for which 
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022

3
LLLT is administered. The individual who performs the assessment will be blinded to the group to which 
each patient belongs.  
To evaluate nerve function, three tests will be conducted, a two-point discrimination (TPD) test, a hard 
stimulus test and soft stimulus test. For the TPD test, the patient will be instructed to close their eyes, 
and a caliper will be placed on the lateral aspect of the patient’s chin. The calipers will start at 0 mm and 
be incrementally opened in .5mm increments, and the first distance felt by the patient as two distinct 
points will be recorded reported in millimeters. For the soft- and hard- stimuli tests, the lower face will 
be divided into eight regions, with four symmetric regions per side. Region 1 will be from the skin on the 
chin at the midsagittal plane laterally 1 cm. Region 2 will be the skin from the edge of Region 1 
extending laterally 1 cm. Region 3 will be the skin from the edge of Region 2 extending laterally 1 cm. 
Region 4 will be the vermillion of thee lower from the midsagittal plane to the commissure. The regions 
will be designated by an “L” for left or “R” for right, plus a number as per the above scheme. Each region 
will be checked for nerve function via two tests, a cotton-swab test and a two test. During the 
evaluation, the patient will be instructed to keep their eyes closed. The cotton-swab test will involve the 
skin in each region being lightly brushed in a 2cm vertical path twice per region, and the patient 
reporting if they feel the contact. Likewise, the toothpick test will involve the skin being slightly 
depressed by the edge of a toothpick in three spots separated by 1 cm each per region, and the patient 
reporting if they feel the contact. The responses will be recorded as positive or negative for soft (swab) 
or hard pressure (toothpick), by region.
Pain will be reported via use of a visual analogue scale (VAS). The patient will rate the intensity of the 
pain on each side of the mandible at each visit. The intensity of the pain will be from zero, meaning 
compete absence of pain, to 10, indicating the maximum amount of pain imaginable. 
Swelling will be measured with a soft measuring tape from the tip of the chin to the lower lobe of the 
ear, bilaterally. The calculation of the swelling index will be done by subtracting the baseline length 
(from the six-week post-operative visit) to the measured length and diving the difference by baseline 
length and multiplying by 100.
Outcomes (primary and secondary)
In this study, the predictor variable was the use of laser therapy versus placebo treatment after 
orthognathic surgery on the mandible. The primary outcome variable was neurosensory disturbance 
recovery by the TPD, hard and soft sensory tests. The secondary outcome variables are pain reduction, 
as measured by change in VAS, and swelling reduction, as measured by soft-ruler measurement of lower 
face.
Sample Size
Published data (13-15) examining the effect of LLLT on IAN functional recovery shows a range of 
improvement versus placebo. The percentage of recovery shows that the LLLT treatment led to 27.3% 
(n=30, not split mouth, standard deviation not reported) (13), 13% (n=12, split mouth, 7.4167 ± 1.62 vs 
8.5000 ± 1.56) (14), and 15% (n= 15, 5.12 + 0.59 vs 5.97 + 0.45) (15) improvement in sensory function, 
with . Additionally, one non-placebo controlled study of patients with long-standing documented 
neurosensory alteration following dental surgery (12) showed 33% improvement over baseline (n=4). 
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022

4
Using these studies, a sample size graph (Figure 1) was plotted in R Stats Package with the effect size 
versus sample size, with the standard deviation set to 0.5 and power set to 0.9. In order to detect an 
effect size of 0.5 with a SD of 0.5 at 90% power a sample size of just over 22 is needed. Therefore, 23 
subjects per arm is required.
Figure 1- Effect size vs. Sample size.
The oral surgery clinic at Jacobi Medical Center treats approximately 50 patients with orthognathic 
surgery of the mandible annually, and has done so routinely for the last decade. Recruiting 46 patients 
to participate, even accounting for potential drop outs or failure to follow-up, should prove feasible.
Risk/Benefit
There are no known risks to low-level laser therapy. 
The potential benefits to the patients are improved course of healing after orthognathic surgery.
Data will be stored on Jacobi shared servers using password-protected spreadsheets, that use codes to 
de-identify patients’ names. The list of patient names that correspond to codes will be saved separately 
in a password-protected spreadsheet, and only the PI will have access the password.
Participant Recruitment
The patient pool for this study will be drawn from regular patients scheduled to undergo orthognathic 
surgery at Jacobi Medical Center. Patients who have been cleared for orthognathic surgery already must 
be in good health and understand the risks of the surgery. The only additional requirements for inclusion 
are 1) the planned surgery includes bilateral sagittal split osteotomies; 2) patients must be free from 
pre-operative inferior alveolar neurosensory deficiencies; 3) the patient cannot have an intra-operative 
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022

5
accidental fracture or rupture of the inferior alveolar nerve. The details of the whole orthognathic 
surgery will be recorded (including maxillary procedure, genioplasty, and direction of positional change 
of the mandible) but will not alter eligibility for enrolment in the study. 
Since 2013, over 30% of the patients treated for orthognathic surgery at Jacobi Medical Center are 
between the ages of 15 and 18, which is in line with orthognathic surgery in general. As such, the study 
aims to include these patients in the potential pool of subjects. Because of the significant portion of 
patients under the age of 18 in general, and their inclusion will allow for age to be examined as a related 
factor in how healing proceeds. Their inclusion will also allow for an adequate sample size.
Informed Consent
Patients who express interest in volunteering for the study will have the risks and benefits of the study 
explained to them, as well as that they may be assigned to either a control or experimental group. The 
details of study participation will be explained, including that the patients will not have any aspect of 
their surgery or post-care altered, other than LLLT treatment. It will be explained that the time 
commitment of the study is the same as the normal post-op care, with the exception of two additional 
visits at 8 weeks and 20 weeks post-op. It will be explained that patients may decided to not volunteer 
and their treatment will not be affected. Likewise, if the patients decide to drop out of the study, their 
treatment will not be affected. Information security will also be discussed with the patient during the 
consent process. All information in the discussion will be provided to the patient in written form, with a 
copy for them to keep. Patients who desire an alternate language will be offered translation services.
Patients over 18, will be given an informed consent form to sign. Patients who are under 18 will be 
asked to sign the informed consent form, to indicate their assent, while a legal guardian, who will also 
be present for the discussion of the risks and benefits of the study, will be asked to sign for consent.
Data analysis
The primary outcome, change in neurosensory deficit, is measured by the three clinical tests, TPD, soft-
stimulus and hard-stimulus.  For TPD, the difference between the LLLT group and placebo group at each 
time point will be compared using an independent t-test, with alpha set at .05. The soft- and hard- 
stimulus tests for each region will be analyzed at each time point with a chi-square test. VAS pain score 
and swelling index will be analyzed using independent t-tests for the measurements on each side at 
each time point, with alpha set at .05. Linear regression will be performed to analyze the relationship of 
the pain, swelling and nerve tests with age, skeletal class, direction and magnitude of mandibular 
movement, and inclusion of genioplasty.
Safety monitoring
While low-level laser therapy has no known adverse effects, safety monitoring of the study participants 
will be conducted in conjunction with their normal post-operative care during the duration of their 
participation, which occurs at each post-surgical visit. As orthognathic post-op care is generally overseen 
by the Jacobi Director of Oral & Maxillofacial Surgery (OMFS), the director will serve as the safety 
monitor. Adverse events during post-op care are reported to the Director of OMFS and documented into 
the patient chart. Any patient reporting an adverse event that is deemed, by the Director of OMFS, as 
clinically significant, will be withdrawn from the study and provided with all appropriate treatment. If 
more than one patient is withdrawn from the study through this mechanism, the study will be halted. 
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022

6
The Director of OMFS will report to the PI any adverse events requiring removal of a patient from the 
study, and the PI will document the adverse effects and provide a report to the IRB.
Citations
1.
Trauner R, Obwegeser H. The surgical correction of mandibular prognathism and retrognathia 
with consideration of genioplasty. II. Operating methods for microgenia and distoclusion. Oral Surg Oral 
Med Oral Pathol. 1957;10(8):787-92; contd.
2.
Al-Bishri A, Barghash Z, Rosenquist J, Sunzel B. Neurosensory disturbance after sagittal split and 
intraoral vertical ramus osteotomy: as reported in questionnaires and patients' records. Int J Oral 
Maxillofac Surg. 2005;34(3):247-51.
3.
Kuroyanagi N, Miyachi H, Ochiai S, Kamiya N, Kanazawa T, Nagao T, et al. Prediction of 
neurosensory alterations after sagittal split ramus osteotomy. Int J Oral Maxillofac Surg. 2013;42(7):814-
22.
4.
Al-Bishri A, Rosenquist J, Sunzel B. On neurosensory disturbance after sagittal split osteotomy. J 
Oral Maxillofac Surg. 2004;62(12):1472-6.
5.
Baas EM, Horsthuis RB, de Lange J. Subjective alveolar nerve function after bilateral sagittal split 
osteotomy or distraction osteogenesis of mandible. J Oral Maxillofac Surg. 2012;70(4):910-8.
6.
Boutault F, Diallo R, Marecaux C, Modiga O, Paoli JR, Lauwers F. [Neurosensory disorders and 
functional impairment after bilateral sagittal split osteotomy: role of the anatomical situation of the 
alveolar pedicle in 76 patients]. Rev Stomatol Chir Maxillofac. 2007;108(3):175-82; discussion 82.
7.
D'Agostino A, Trevisiol L, Gugole F, Bondi V, Nocini PF. Complications of orthognathic surgery: 
the inferior alveolar nerve. J Craniofac Surg. 2010;21(4):1189-95.
8.
Reddy GK. Photobiological basis and clinical role of low-intensity lasers in biology and medicine. 
J Clin Laser Med Surg. 2004;22(2):141-50.
9.
Ezzati K, Fekrazad R, Raoufi Z. The Effects of Photobiomodulation Therapy on Post-Surgical Pain. 
J Lasers Med Sci. 2019;10(2):79-85.
10.
Hamid MA. Low-level Laser Therapy on Postoperative Pain after Mandibular Third Molar 
Surgery. Ann Maxillofac Surg. 2017;7(2):207-16.
11.
Khullar SM, Emami B, Westermark A, Haanaes HR. Effect of low-level laser treatment on 
neurosensory deficits subsequent to sagittal split ramus osteotomy. Oral Surg Oral Med Oral Pathol Oral 
Radiol Endod. 1996;82(2):132-8.
12.
Ozen T, Orhan K, Gorur I, Ozturk A. Efficacy of low level laser therapy on neurosensory recovery 
after injury to the inferior alveolar nerve. Head Face Med. 2006;2:3.
13.
Fuhrer-Valdivia, A., A. Noguera-Pantoja, V. Ramirez-Lobos, and P. Sole-Ventura. "Low-Level 
Laser Effect in Patients with Neurosensory Impairment of Mandibular Nerve after Sagittal Split Ramus 
Osteotomy. Randomized Clinical Trial, Controlled by Placebo." Med Oral Patol Oral Cir Bucal 2014;19(4): 
e327-34. 
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022

7
14.
Haghighat A, Khosrawi S, Tamizifar A, Haghighat M. Does Low-Level Laser Photobiomodulation 
Improve Neurosensory Recovery After Orthognathic Surgery? A Clinical Trial With Blink Reflex. J Oral 
Maxillofac Surg. 2021;79(3):685-93.
15.
Eshghpour, M., B. Shaban, F. Ahrari, M. Erfanian, and E. Shadkam. "Is Low-Level Laser Therapy 
Effective for Treatment of Neurosensory Deficits Arising from Sagittal Split Ramus Osteotomy?". J Oral 
Maxillofac Surg 2017; 75(10): 2085-90.
16.       Bittencourt MA, Paranhos LR, Martins-Filho PR. Low-level laser therapy for treatment of 
neurosensory disorders after orthognathic surgery: A systematic review of randomized clinical trials. 
Med Oral Patol Oral Cir Bucal. 2017;22(6):780-7.
17.
Firoozi P, Keyhan SO, Kim SG, Fallahi HR. Effectiveness of low-level laser therapy on recovery 
from neurosensory disturbance after sagittal split ramus osteotomy: a systematic review and meta-
analysis. Maxillofac Plast Reconstr Surg. 2020;42(1):41.
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022
IRB NUMBER: 2021-12990
IRB APPROVAL DATE: 03/16/2022