Abstract
Background:
The nevus of Ota is an uncommon pigmentary skin condition that causes bluish-gray pigmentation and is traditionally treated with a Q-switched laser. Emerging evidence suggests that the 755-nanometer picosecond alexandrite laser is a safe and effective therapeutic option. We sought to determine the overall effectiveness and safety profile of the 755-nanometer (nm) picosecond alexandrite laser for managing nevus of Ota.
Methods:
We reviewed 6 databases for studies that addressed the safety as well as efficacy profile of the 755-nm picosecond alexandrite laser for nevus of Ota. Ten studies, including 558 individuals with nevus of Ota, were included. The main outcomes were the rate of excellent clinical response and reported side effects encompassing erythema as well as post-inflammatory pigmentary alterations, including both hyperpigmentation and hypopigmentation. Review Manager Version 5.4 and Comprehensive Meta-Analysis v3 software were used for data analysis.
Results:
The pooled excellent clinical response rate for the 755-nm picosecond alexandrite laser was found to be 36.8% (95% confidence interval [24.4–51.2%], P = .642). Post-inflammatory hyperpigmentation and hypopigmentation were each observed in 20.6% and 12.2% of the cases (P-value < .001), respectively. Post-inflammatory erythema, assessed in 2 studies (n = 23), demonstrated a pooled prevalence of 45.2% (95% confidence interval: 12.9–82.2%).
Conclusion:
The 755-nm picosecond alexandrite laser demonstrated moderate effectiveness and a favorable safety profile in the treatment of nevus of Ota. Pigmentary complications occurred at relatively low rates across the included studies. Further high-quality prospective and randomized controlled trials are required to confirm long-term effectiveness and safety.
Keywords: lasers, nevus of Ota, picosecond lasers, pigmentary disorders
1. Introduction
An uncommon and harmless pigmentary disorder marked with brown or bluish-gray spots is known as nevus of Ota.[1] It usually affects skin areas that receive blood from the ophthalmic and maxillary branches of the trigeminal nerve.[1] This condition is seen more often among the Asian population, but it can also affect people of other ethnic backgrounds.[2] Moreover, the rate of occurrence is 0.03%.[2] It is not common to find nevus of Ota in adults; it usually shows up in young children.[3] Patients with nevus of Ota may have mental health problems because of its disfiguring appearance, which may make caregivers want to seek medical attention.[4]
Managing nevus of Ota in its early stages is one of the ongoing therapeutic challenges.[5,6] Geronemus et al was the first to suggest using Q-switched lasers to treat nevus of Ota in a small study with 15 individuals.[7] Recent research suggests that the results of treatment may eventually plateau with Q-switched lasers.[8] Also, using Q-switched lasers has often been linked to side effects like erosions, hyperpigmentation, and hypopigmentation.[6] Because of this, many patients may not be able cope with it.[6]
Recently, picosecond lasers have demonstrated remarkable efficacy at eliminating tattoos.[9,10] For example, Brauer reported that the 755-nanometer (nm) picosecond alexandrite laser could eradicate up to 75% of pigmentation in green and/or blue tattoos after merely 1 or 2 treatments.[10] The very short pulse length of picosecond lasers is fundamental to their therapeutic efficacy, largely via photoacoustic and photomechanical mechanisms that disintegrate pigment particles while minimizing heat transfer to adjacent tissues.[11] The 755-nm picosecond alexandrite laser has recently garnered significant attention for its efficacy in treating pigmented conditions.
Zhao et al described the use of the 755-nm picosecond alexandrite laser in 306 children with nevus of Ota.[4] The average pigment removal was determined to be 79.1% following about 2 sessions.[4] Likewise, Lin YT et al did a retrospective study on 86 Taiwanese patients with nevus of Ota.[6] They found that 96.5% of them got 95% to 100% of their pigment cleared after an average of 4.3 sessions, with only minor and temporary side effects.[6]
A 2021 meta-analysis and systematic review evaluated the safety as well as effectiveness of various laser treatments, including the 755-nm picosecond alexandrite laser, for nevus of Ota. The study demonstrated that the 755-nm picosecond laser had a 100% success rate, but this was only based on 2 studies, which makes it difficult to apply the results to other situations.[12] Our current meta-analysis and systematic review builds on these results by including newer studies and a wider range of patient groups. This gives us a more complete and reliable understanding of the safety as well as effectiveness profile of the 755-nm picosecond alexandrite laser for treating nevus of Ota.
2. Methods
Registration of this study was completed in the Prospective Register of Systematic Reviews with protocol ID: CRD420251044271. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and used the Population, Intervention, Comparator, Outcome framework: populations (P): patients with nevus of Ota; intervention (I): 755-nm picosecond alexandrite laser; comparator (C): other laser treatments, placebo, or no treatment; outcome (O): efficacy and adverse effects.[13]
2.1. Search strategy
In April 2025, we performed an extensive literature review utilizing multiple databases, including PubMed, Google Scholar, EBSCO, Web of Science, Embase, and Scopus (as shown in Table 1). Subsequently, we manually reviewed the bibliographies of all identified articles and carried out forward and backward citation tracking throughout the full text review to find other relevant publications.
Table 1.
Search strategy for different databases.
| Database | Date | Keywords | Results | |
|---|---|---|---|---|
| 1 | PubMed | April 4, 2025 | (“Nevus of Ota”[MeSH] OR “nevus of Ota” OR “oculodermal melanocytosis” OR “Ota nevus”) AND (“Picosecond laser” OR “picosecond lasers” OR “755-nm alexandrite laser” OR “picosecond alexandrite laser” OR “picosecond 755-nm alexandrite laser”) |
13 |
| 2 | Google Scholar | April 4, 2025 | (“Nevus of Ota”[MeSH] OR “nevus of Ota” OR “oculodermal melanocytosis” OR “Ota nevus”) AND (“Picosecond laser” OR “picosecond lasers” OR “755-nm alexandrite laser” OR “picosecond alexandrite laser” OR “picosecond 755-nm alexandrite laser”) |
13 |
| 3 | Web of science | April 4, 2025 | (“Nevus of Ota”[MeSH] OR “nevus of Ota” OR “oculodermal melanocytosis” OR “Ota nevus”) AND (“Picosecond laser” OR “picosecond lasers” OR “755-nm alexandrite laser” OR “picosecond alexandrite laser” OR “picosecond 755-nm alexandrite laser”) |
31 |
| 4 | Ebsco | April 4, 2025 | (“Nevus of Ota”[MeSH] OR “nevus of Ota” OR “oculodermal melanocytosis” OR “Ota nevus”) AND (“Picosecond laser” OR “picosecond lasers” OR “755-nm alexandrite laser” OR “picosecond alexandrite laser” OR “picosecond 755-nm alexandrite laser”) |
18 |
| Embase | April 16, 2025 | (“nevus ota”:ti OR “nevus of ota”:ti OR “oculodermal melanocytosis”:ti) AND picosecond:ti AND laser:ti | 23 | |
| April 16, 2025 | (“nevus ota”:ti OR “nevus of ota”:ti OR “oculodermal melanocytosis”:ti) AND alexandrite:ti AND laser:ti | 29 | ||
| Scopus | April 16, 2025 | (TITLE (Nevus of Ota) OR TITLE (Nevus Ota) OR TITLE (oculodermal megalocytosis) AND TITLE (Picosecond) OR TITLE (alexandrite) AND TITLE (Laser)) | 46 |
2.2. Study selection
The Rayyan collaboration platform was utilized to screen articles based on title and abstract (https://www.rayyan.ai/).[14] Our inclusion criteria consisted of: studies that included patients with nevus of Ota of any age, sex, ethnicity, or Fitzpatrick skin type; studies that reported at least one effectiveness outcome such as percentage of lesion clearance or pigmentation reduction, alongside safety results, such as side effects, associated with the 755-nm picosecond alexandrite laser; randomized controlled trials, non-randomized comparative studies, and both prospective and retrospective studies; full-text studies published solely in English. The exclusion criteria included: studies that did not utilize the 755-nm picosecond alexandrite laser as a treatment method; studies that combined results from multiple laser therapies without providing separate data for the 755-nm picosecond alexandrite laser; studies that included other pigmentary disorders such as melasma or nevus spilus without reporting separate data for nevus of Ota; studies that did not report relevant efficacy or safety outcomes; case reports, case series, review articles, editorial letters, abstracts, animal studies, or in vitro research; studies published in languages other than English, unless there is an available full-text English translation.
2.3. Data extraction
Using a predesigned standardized data extraction form, 2 authors extracted data independently from the figures, tables and text of all included studies. For the purpose of ensuring accuracy, a third author independently examined the data extraction process, verifying each extracted data point against the original study materials to detect as well as address inconsistencies or missing information. In addition to patient-related information like age, sex, and Fitzpatrick skin type, the retrieved data included research characteristics including the first author’s last name, study area, design, and study time. Details regarding the 755-nm picosecond alexandrite laser protocol were also extracted, such as pulse duration, fluence, spot size, frequency, number of sessions, interval between sessions, and follow-up duration. The efficacy outcomes data extracted was the rate of excellent response. An excellent clinical response was defined as a reduction or lightening of the lesion by ≥75% from the baseline, evaluated through clinical examinations by a physician or photographic assessments. At last, safety outcomes, which included adverse skin reactions posttreatment with the 755-nm picosecond alexandrite laser, such as post-inflammatory hyperpigmentation, post-inflammatory hypopigmentation, and post-inflammatory erythema, were recorded.
2.4. Risk of bias and quality assessment
The Cochrane Collaboration’s bias assessment tool was employed to evaluate the risk of bias in the included randomized clinical trials.[15] The quality of the observational studies was evaluated using the National Institute of Health quality assessment method.[16] According to this quality assessment, the studies were categorized as good, fair, or poor based on scores over 65%, ranging from 30 to 65%, or below 30%, respectively. A domain was designated as “Yes” when the parameter was controlled, and as “No” when it was not.
2.5. Statistical analysis
Standardized mean difference was utilized to analyze continuous variables. Data presented in median and range, mean and range, as well as mean with 95% confidence interval (CI), were converted to mean and standard deviation using the equations from Hozo et al.[17] To evaluate outcomes, event rates and 95% CIs were computed for each study, capturing both prevalence of response and risk of complications. These estimates were then synthesized into a pooled summary proportion with 95% CIs. Dichotomous variables were analyzed using risk ratios or odds ratios (ORs). The choice of analytical model depended on assumptions regarding heterogeneity: a fixed-effect model was applied when a uniform effect size was expected, and a random-effects model when variation across studies was presumed. Statistical heterogeneity was appreciated using the Higgins I2 statistic, at the value >50%, and the Cochrane Q (Chi2 test), at the value of P < .10.[18] Data analysis was performed using Review Manager version 5.4 (The Cochrane Collaboration, Copenhagen, Denmark) and Comprehensive Meta-Analysis v3 software (Biostat, Inc., Englewood).[19,20] A P-value of <.05 was considered statistically significant.
3. Results
The literature search across 6 databases initially yielded 173 articles. Following title and abstract screening, 108 studies were considered relevant. Nineteen full-text articles were assessed, and finally, 9 were selected for data extraction. Additionally, one article was identified through citation tracking, bringing the total to 10 articles eligible for the purpose of meta-analysis and systematic review (as shown in Fig. 1).
Figure 1.
PRISMA flow chart showing the process of the literature search for the systematic review. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analysis.
3.1. Demographic characteristics of the included studies
The current systematic review included 10 articles, involving a total of 558 patients diagnosed with nevus of Ota.[4–6,21–27] Three articles included participants from China, 3 from Japan, and 2 from Taiwan. Among the studies, 7 adopted a retrospective design, while 2 were prospective, and 1 was a randomized, split-lesion, controlled trial. The mean age of participants ranged between 3 months and 71 years. The sample included 165 males and 414 females. Specifically, 158 patients had Fitzpatrick Skin Type III, and 300 had Type IV. The average pulse duration ranged from 550 to 750 picoseconds, and the average fluence ranged between 0.71 and 6.37 J/cm2. The frequency of the alexandrite laser was reported to range between 2.5 and 10 Hz, with the average spot size ranging from 2 to 5 mm.
Participants underwent an average of 1 to 6 treatment sessions, with intervals between sessions lasting from 4 to 6 weeks. The follow-up interval reported in the studies ranged between 3 and 60 months. All included observational studies were of good quality, scoring between 66.66% and 75%.[4–6,21,23–27] Ge et al showed an unclear risk for random sequence generation bias, an unclear risk of allocation concealment bias, and a low risk of performance, detection, and attribution biases[22] (as shown in Table 2).
Table 2.
Characteristics of the included studies.
| Study ID | Study region | Study design | Study period | Sample size | Picosecond alexandrite laser | Laser device manufacturer | Age (yr) | Gender | Fitzpatrick skin type | Protocol of picosecond alexandrite laser | Follow-up (mo) | Quality assessment | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Males | Females | Type III | Type IV | Pulse duration | Fluence (J/cm2) | Spot size (mm) | Frequency | Number of sessions | Interval between sessions | |||||||||||||
| Number | Range | Number | Number | Number | Number | % | Decision | |||||||||||||||
| 1 | BSN et al[4] | China | Retrospective | NR | 305 | 755-nm | PicoSure, Cynosure | 3 mo to 12 yr | 114 | 191 | 76 | 230 | 750 ps | 2.83–4.07 J/cm2 | 2.5–3.0 mm | NR | 1–6 sessions | 3–6 mo | 36–60 mo | 75% | Good | |
| 2 | Chan et al[21] | Japan | Retrospective | October 2013 to November 2014 | 4 | 755-nm | PicoSure, Cynosure | 23.9 ± 16.2 yr | NR | NR | NR | 1 | NR | 1.76–4.80 J/cm2 | 2.3–3.8 mm | 2.5–5.0 Hz | 3–4 sessions | 4–6 wk | 6 mo | 66.66% | Good | |
| 3 | Ge et al[22] | China | A randomized, split-lesion, controlled trial | NR | 53 | 755-nm | PicoSure, Cynosure | 18 to 54 yr | 16 | 37 | 8 | 48 | 750 ps | 1.59–6.37 J/cm2 | 2.0–4.0 mm | 5 Hz | 5.26 sessions | 1.59–6.37 J/cm2 | 3 mo | – | – | |
| 4 | Hu et al[5] | Taiwan | Retrospective | April 2017 and March 2019 | 36 | 755-nm | PicoSure, Cynosure | 19 to 58 yr | 0 | 36 | NR | NR | 650 ps | 2.73–3.98 J/cm2 | 2.4–2.9 mm | NR | 1–4 sessions | 3–12 mo | ≥3 mo | 66.66% | Good | |
| 5 | Imagawa et al[23] | Japan | Prospective study | NR | 9 | 755-nm | PicoSure, Cynosure | 24 to 70 yr | 2 | 7 | 4 | 5 | 550 ps | 2.33–3.36 J/cm2 | 2.5–3 mm | NR | 4.2 (mean) | 6–8 wk | 6 mo (posttreatment) | 66.66% | Good | |
| 6 | Koh et al[24] | Singapore | Retrospective | NR | 18 | 755-nm | PicoSure, Cynosure | 22 to 59 yr | 4 | 14 | NR | NR | 750 ps | 1.02–2.92 J/cm2 | 2.8–5 mm | 5–10 Hz | 1–6 sessions | 2 mo | NA | 66.66% | Good | |
| 7 | Levin et al[25] | USA | Retrospective | January 2011 to December 2013 | 17 | 755-nm | Picolase, Cynosure | 1 to 71 yr | 6 | 36 | NR | NR | 750–900 ps | 0.71–4.07 J/cm2 | 2.5–6 mm | NR | Mean: 4.12 (SD: 2.23) | NA | (mean: 18.21 wk) | 66.66% | Good | |
| 8 | Sakio et al[26] | Japan | Retrospective | June 2015 to August 2017 | 15 | 755-nm | PicoSure, Cynosure | 10 mo to 65 yr | 3 | 12 | NR | NR | 750 ps | 4.07–6.37 J/cm2 | 2.2–2.5 mm | NR | 2–3 sessions | Average: 4.1 mo | 3 mo | 66.66% | Good | |
| 9 | Yang et al[6] | Taiwan | Retrospective | January 2017 and September 2020 | 86 | 755-nm | PicoSure, Cynosure | 3.6 ± 2.3 yr | 17 | 69 | 70 | 16 | 750 ps | 1.96–2.08 J/cm2 | 3.5–4.0 mm | NR | 4.3 (4–6) | 3–4 mo | 9–36 (mean: 20.9) | 66.66% | Good | |
| 10 | Zhou et al[27] | China | Prospective self-controlled trial | June 2019 to July 2021 | 15 | 755-nm | PicoSure, Cynosure | 4 mo to 29 yr | 3 | 12 | NR | NR | NR | 5.25–6.37 J/cm2 | 2 mm | 5 Hz | 2–5 sessions | 3 mo | 10–24 mo | 66.66% | Good | |
Hz = hertz, J/cm2 = joules per square centimeter, mm = millimeter, nm = nanometer, NR = not reported, ps = picosecond, SD = standard deviation.
3.2. Outcomes of the picosecond alexandrite laser
3.2.1. Excellent response
Seven articles, including 493 patients, evaluated the prevalence of excellent response after picosecond alexandrite laser among patients with nevus of Ota.[4–6,21–23,26] In the random-effects model (I2 = 87.8%, P < .001), the prevalence of excellent response was estimated at 36.8%, with a 95% confidence interval of 24.4% to 51.2% (P = .642) (as shown in Fig. 2). We conducted a leave-one-out analysis to determine the effect of each of the studies on the observed heterogeneity. Our leave-one-out analysis (as shown in Fig. S1, Supplemental Digital Content, https://links.lww.com/MD/R382) indicated that none of the included studies significantly contributed to the observed heterogeneity. Omission of each of the studies did not change the heterogeneity by >5% (as shown in Fig. S1, Supplemental Digital Content, https://links.lww.com/MD/R382).
Figure 2.
Forest plot of summary analysis of the event rate and 95% CI of excellent response after picosecond alexandrite laser in patients with nevus of Ota. CI = confidence interval.
Two studies compared the odds of excellent response between the picosecond alexandrite laser and the Q-switched laser.[22,25] There was no statistically significant difference between both groups (OR: 0.748, 95% CI: 0.213–2.631, P = .651) in the random-effects model (I2 = 28.3%, P = .23) (as shown in Fig. 3).
Figure 3.
Forest plot of summary analysis of the event rate and 95% CI of excellent response after picosecond alexandrite laser and Q-switched laser in patients with nevus of Ota. CI = confidence interval.
3.2.2. Complete clearance
Three studies separately reported the number of patients who had complete clearance of the lesions.[4,6,22] The pooled prevalence of complete clearance was 28% with a 95% CI between 4.1% and 78% (as shown in Fig. 4). The analysis however, had significant heterogeneity (99.8, P = .00). A leave-one-out analysis identified BSN et al, as the study that contributed to this observed heterogeneity. Omitting this study reduced the heterogeneity to 0% (as shown in Fig. S2, Supplemental Digital Content, https://links.lww.com/MD/R382).
Figure 4.
Forest plot of summary analysis of the event rate and 95% CI of complete clearance after picosecond alexandrite laser in patients with nevus of Ota. CI = confidence interval.
3.2.3. Post-inflammatory hyperpigmentation
Eight articles, including 501 patients, evaluated the risk of post-inflammatory hyperpigmentation after picosecond alexandrite laser among patients with nevus of Ota.[4–6,22,23,25–27] The prevalence of post-inflammatory hyperpigmentation was 20.6% (95% CI: 11.5–34.3%, P < .0001) in the random-effects model (I2 = 77.5%, P < .0001) (as shown in Fig. 5). A leave-one-out analysis identified Sakio et al, as the study that significantly contributed to the observed heterogeneity. Omitting this study reduced the heterogeneity to 46.6% (as shown in Fig. S3, Supplemental Digital Content, https://links.lww.com/MD/R382).
Figure 5.
Forest plot of summary analysis of the event rate and 95% CI of post-inflammatory hyperpigmentation after picosecond alexandrite laser in patients with nevus of Ota. CI = confidence interval.
3.2.4. Post-inflammatory hypopigmentation
Eight articles, including 502 patients, evaluated the risk of post-inflammatory hypopigmentation after picosecond alexandrite laser among patients with nevus of Ota.[4–6,21–24,27] The risk of post-inflammatory hypopigmentation was 12.2% (95% CI: 4.7–28.1, P < .0001) in the random-effects model (I2 = 84.3%, P < .001) (as shown in Fig. 6). A leave-one-out analysis identified BSN et al, as the study that significantly contributed to the observed heterogeneity, as its omission reduced the heterogeneity to 57.4% (as shown in Fig. S4, Supplemental Digital Content, https://links.lww.com/MD/R382).
Figure 6.
Forest plot of summary analysis of the event rate and 95% CI of post-inflammatory hypopigmentation after picosecond alexandrite laser in patients with nevus of Ota. CI = confidence interval.
3.2.5. Post-inflammatory erythema
Two articles, including 23 patients, evaluated the risk of post-inflammatory erythema after picosecond alexandrite laser among patients with nevus of Ota.[24,26] In the random-effects model (I2 = 87.8%, P < .001), the risk of post-inflammatory erythema was 45.2% with a 95% CI that ranged from 12.9% to 82.2% (P = .828) (as shown in Fig. 7).
Figure 7.
Forest plot of summary analysis of the event rate and 95% CI of post-inflammatory erythema after picosecond alexandrite laser among patients with nevus of Ota. CI = confidence interval.
4. Discussion
Managing pigmentary disorders continues to pose challenges for dermatologists on a daily basis.[28] Formerly, Q-switched nanosecond lasers, operating at various wavelengths, were the predominant tools for treating pigmented lesions.[28] More recently, picosecond lasers, which have pulse durations roughly 70 times shorter than those of Q-switched lasers, have been introduced.[28] These shorter pulse durations lead to more intense damage to pigmented chromophores and were first reported as effective for tattoo removal by Ross in 1990.[11,29] Since that time, multiple studies have shown that picosecond lasers enable faster clearance of tattoos, especially those that are blue-green and significantly better in eliminating multicolored tattoos compared to Q-switched nanosecond lasers.[10,30] Moreover, picosecond lasers have lately demonstrated considerable efficacy in treating various endogenous pigmentary disorders, such as nevus of Ota.[25,29,31]
To explore this promising application further, a meta-analysis and systematic review was performed of 10 studies involving a total of 558 patients treated with the 755-nm picosecond alexandrite laser for nevus of Ota. The demographic characteristics of the included participants indicated a predominance of female patients and Fitzpatrick skin types of III and IV, along with a wide age range and varied treatment parameters across studies.
In total, the pooled prevalence of excellent clinical response among individuals who received therapy with the 755-nm picosecond alexandrite laser was 36.8% (95% CI [24.4–51.2%], P = .642), although significant heterogeneity was noted (I2 = 78.7%), reflecting variability in treatment results among studies. Across 2 studies that directly compared the 755-nm picosecond laser with Q-switched lasers, the odds of achieving an excellent clinical response did not differ significantly (OR = 0.748, 95% CI: 0.213–2.631, P = .651), indicating comparable efficacy between the 2 modalities. While no substantial difference in efficacy was noted relative to Q-switched lasers, picosecond lasers may provide clinical benefits through primarily photomechanical pigment fragmentation with lower thermal diffusion, correlating with a reduced risk of pigmentary complications and potentially fewer treatment sessions.[11,29]
Regarding safety and adverse effects, the 755-nm picosecond alexandrite laser showed a favorable safety profile. Specifically, the prevalence of post-inflammatory hyperpigmentation and hypopigmentation was 20.6% and 12.2% (P < .001), respectively. These pigmentary changes occurred at rates that were comparable to or lower than those reported for Q-switched lasers, suggesting a favorable safety profile. Additionally, post-inflammatory erythema was reported less frequently and was evaluated in only 2 studies (n = 23), showing a pooled prevalence of 45.2% (95% CI: 12.9–82.2%, P-value = .828). Overall, the findings suggest that the 755-nm picosecond laser provides moderate efficiency while posing a low risk of complications related to pigmentation.
The outcomes of this review are consistent with previous reports regarding the application of picosecond lasers for pigmentary disorders. Previous research has demonstrated positive outcomes in treating nevus of Ota with Q-switched lasers, reporting excellent clinical efficacy rates ranging from 40% to 60%, varying by laser wavelength and treatment protocols.[7,32,33] We found a pooled excellent response rate of 36.8% (95% CI: 24.4–51.2%) with the 755-nm picosecond alexandrite laser, indicating a broadly comparable efficacy to Q-switched lasers. Conversely, a 2021 systematic review and meta-analysis that compared different lasers reported a 100% success rate, defined as >70% lesion clearance, for the picosecond laser.[12] However, these findings, while encouraging, were based on only 2 studies assessing picosecond lasers, limiting the robustness of their conclusions. In contrast, our review included a greater number of studies, contributing to a more comprehensive conclusion. Moreover, while previous literature has highlighted the risk of pigmentary complications, especially post-inflammatory hyperpigmentation, associated with Q-switched lasers, our pooled analysis revealed a relatively low occurrence (11%) of such events when using picosecond lasers. Shen et al reported that one-third of their patients treated with Q-switched laser experienced post-inflammatory hyperpigmentation.[34]
This review offers significant insights; yet it is essential to recognize its limitations. The articles incorporated in this meta-analysis as well as systematic review were predominantly retrospective, exhibiting diverse study designs. This has the potential to introduce selection bias and limit the strength of the conclusions drawn. Second, by only including studies in English, there may have been language bias, and important data published in other languages might have been excluded. Third, notable heterogeneity existed in treatment parameters, follow-up durations, and methods of outcome assessment, which could have led to the high I2 values noted in the pooled analysis. Fourth, inconsistent reporting of outcome measures, such as clinical severity scores and adverse events, may have reduced the accuracy of the pooled analysis. Fifth, in post-inflammatory erythema, the wide confidence interval and nonsignificant P-value signify considerable imprecision, possibly attributable to the small sample size, hence constraining the reliability of this estimate. However, this evaluation exhibits significant strengths. Based on current evidence, it is the first meta-analysis and systematic review solely focused on assessing the 755-nm picosecond alexandrite laser for nevus of Ota treatment, synthesizing data from 10 studies encompassing a total of 558 patients. Furthermore, this review incorporates a larger sample size and integrates more recent studies that were not considered in prior reviews.[12] In addition, our analysis provides a thorough examination of both efficacy and safety results associated with 755-nm picosecond lasers.
5. Conclusion
The 755-nm picosecond alexandrite laser demonstrated moderate efficacy, with a pooled excellent clinical response rate of 36.8%, and a generally favorable safety profile in the treatment of nevus of Ota. By incorporating a larger number of studies and patients than previous reviews, this analysis provides a comprehensive synthesis of the available evidence. Nevertheless, further high-quality prospective and randomized controlled trials are needed to better define long-term effectiveness and safety.
Author contributions
Conceptualization: Mishari Tariq Alrubaiaan, Ahmed Hisham Almajed.
Data curation: Mishari Tariq Alrubaiaan, Ahmed Hisham Almajed.
Formal analysis: Mishari Tariq Alrubaiaan, Ahmed Hisham Almajed, Latifah Albrahim.
Funding acquisition: Mishari Tariq Alrubaiaan, Ahmed Hisham Almajed.
Investigation: Mishari Tariq Alrubaiaan, Ahmed Hisham Almajed, Saif Alagha, Latifah Albrahim, Khalid Nabil Nagshabandi.
Methodology: Mishari Tariq Alrubaiaan, Ahmed Hisham Almajed, Saif Alagha, Futun Abdulhadi Alsallom, Khalid Nabil Nagshabandi.
Project administration: Mishari Tariq Alrubaiaan.
Resources: Mishari Tariq Alrubaiaan, Ahmed Hisham Almajed, Futun Abdulhadi Alsallom, Khalid Nabil Nagshabandi.
Software: Mishari Tariq Alrubaiaan, Futun Abdulhadi Alsallom, Khalid Nabil Nagshabandi.
Supervision: Lamia Alakrash.
Validation: Mishari Tariq Alrubaiaan, Latifah Albrahim, Khalid Nabil Nagshabandi, Lamia Alakrash.
Visualization: Mishari Tariq Alrubaiaan, Latifah Albrahim, Khalid Nabil Nagshabandi, Lamia Alakrash.
Writing – original draft: Mishari Tariq Alrubaiaan, Saif Alagha, Futun Abdulhadi Alsallom, Latifah Albrahim, Khalid Nabil Nagshabandi.
Writing – review & editing: Mishari Tariq Alrubaiaan, Saif Alagha, Futun Abdulhadi Alsallom, Latifah Albrahim, Khalid Nabil Nagshabandi.
Supplementary Material
Abbreviations:
- CI
- confidence interval
- nm
- nanometer
- OR
- odds ratio
The study has been registered in Prospective Register of Systematic Reviews (PROSPERO) with the protocol number ID: CRD420251044271.
The authors have no funding and conflicts of interest to disclose.
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
Supplemental Digital Content is available for this article.
How to cite this article: Alrubaiaan MT, Almajed AH, Alagha S, Alsallom FA, Albrahim L, Nagshabandi KN, Alakrash L. Investigating the efficacy and safety of the 755-nm picosecond alexandrite laser in treating nevus of Ota: A systematic review and meta-analysis. Medicine 2026;105:8(e47692).
Contributor Information
Ahmed Hisham Almajed, Email: ahmeed.almajed7@gmail.com.
Saif Alagha, Email: saifalagha01@gmail.com.
Futun Abdulhadi Alsallom, Email: futunabdulhadi@gmail.com.
Latifah Albrahim, Email: latifahalbrahim@gmail.com.
Khalid Nabil Nagshabandi, Email: Khaloed23@gmail.com.
Lamia Alakrash, Email: l.alakrash@hotmail.com.
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