
==== Front
J Curr Ophthalmol
J Curr Ophthalmol
JCO
J Curr Ophthalmol
Journal of Current Ophthalmology
2452-2325
Wolters Kluwer - Medknow India

JCO-35-350
10.4103/joco.joco_164_23
Original Article
Adverse Events of Femtosecond-Assisted Laser-Assisted In situ Keratomileusis: A Manufacturer and User Facility Device Experience Database Study
Hong Sungmin 1
Yu Austin 2
Wong Amanda 3
Adamovich-Zeitlin Richard 1
Shah Paras 45
Minaya Josue 1
Wang Carol 1
Peng Travis 1
Saleem Matthew 1
Lau Nathan 56
Gupta Rohun 6
Gorski Matthew 45
Winokur Jules 45
Zhu Daniel 45
1 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
2 Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
3 Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA
4 Manhattan Eye, Ear and Throat Hospital, New York, New York, USA
5 Northwell Health Eye Institute, Great Neck, New York, USA
6 Department of Ophthalmology, Rush University Medical Center, Chicago, Illinois, USA
Address for correspondence: Daniel Zhu, Northwell Health Eye Institute, Great Neck, New York, New York, USA. E-mail: dzhu@northwell.edu
Oct-Dec 2023
10 8 2024
35 4 350354
12 8 2023
18 11 2023
28 12 2023
Copyright: © 2024 Journal of Current Ophthalmology
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
Purpose:

To analyze the United States Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database, which contains reports of adverse events involving medical devices, and characterize the most common adverse events of femtosecond (FS) laser-assisted in situ keratomileusis (LASIK).

Methods:

The MAUDE database was queried on May 19, 2022, for adverse events involving the ophthalmic FS laser reported from January 2012 to April 2022. Reports unrelated to LASIK procedures were excluded. Data extraction was performed on these reports, including the type of adverse event and whether surgery was successfully completed. Frequency analysis was performed using the Statistical Package for the Social Sciences.

Results:

From the 3491 reported adverse events involving the FS laser system, 1136 met the inclusion criteria. Of the 672 cases where outcomes were reported, 476 were successfully completed and 196 were aborted. The most common intraoperative complications were incomplete cut (42.8%), thinner than intended flap (17.6%), and difficulty lifting the flap (12.0%). FS-related complications included opaque bubble layer (2.3%), air bubbles in the anterior chamber (2.4%), and vertical gas breakthrough (4.1%). Other device-related intraoperative complications included suction loss (10.2%), difficulty docking (2.4%), and laser malfunction (2.0%). The most common postoperative complications were diffuse lamellar keratitis (DLK) (7.8%) and rainbow glare (4.6%).

Conclusion:

The most common intraoperative FS-assisted LASIK complication in the MAUDE database was an incomplete flap. The most common postoperative complication was DLK. This study is the first to investigate FS-assisted LASIK adverse events in the MAUDE database. It can raise awareness of real-world surgical complications and help ophthalmologists better counsel and treat patients.

Adverse events
Complications
Laser-assisted in situ keratomileusis
Ophthalmology
Refractive surgery
United States Food and Drug Administration
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pmcINTRODUCTION

Since its introduction in the early 1990s, laser-assisted in situ keratomileusis (LASIK) has become the most common refractive surgery worldwide and a popular alternative to glasses and contact lenses. Creation of the lamellar corneal flap, a critical step in LASIK, was traditionally done through a mechanical microkeratome (MMK). Since then, innovations in instrumentation and technology have led to safer modern MMKs with the United States Food and Drug Administration’s (FDA’s) approval of femtosecond-assisted LASIK (FS-LASIK) in 2001.1 While studies have shown that FS-assisted LASIK has a more predictable outcome and lower incidence of flap-related complications compared to MMK, there are also unique complications associated with its use.234

Intraoperative complications associated with FS-LASIK include subconjunctival hemorrhages, which have been seen in nearly one-third of cases, and suction loss which may occur when there is an asymmetric tear meniscus around the patient interface, potentially leading to an incomplete flap.56 In addition to intraoperative complications, postoperative complications must also be monitored. These complications include pathologies ranging from dry eye to pressure-induced stromal keratitis in the early setting as well as regression and epithelial ingrowth later in the postoperative course.5

In our study, we analyze the wide array of complications associated with FS-LASIK in the FDA’s Manufacturer and User Facility Device Experience (MAUDE) database and document the number of reported complications over the past decade. MAUDE collects and stores complication reports from mandatory reporters (e. g., device manufacturers, hospitals, and surgery centers), as well as voluntary reporters (e. g., physicians, other clinical personnel, and patients) and is updated monthly for adverse events surrounding medical devices. While prior studies have analyzed complications reported to MAUDE for FS laser-assisted cataract surgery (FLACS) and microinvasive glaucoma surgery, no studies have examined reported complications of FS-LASIK.78 The objective of this paper is to report on intraoperative and postoperative complications of FS-LASIK reported to the MAUDE database.

METHODS

The MAUDE database was queried on May 19, 2022 for adverse events involving the FS laser reported from January 2012 to April 2022. Only entries pertaining to FS-LASIK were included. Reports that did not provide adequate information on whether the procedure pertained to FS-LASIK were excluded. Each entry was categorized by date of report and manufacturer. Intraoperative complications were categorized by whether surgery was successfully completed, aborted, or had an unknown result. They were also subdivided by whether they were dissection, flap, FS laser, or lifting-related. Postoperative complications were categorized by time of onset, presence of treatment, and resolution if specified. Entries frequently had more than one complication described, in which case each complication was marked independently. Frequency analysis was performed using the Statistical Package for the Social Sciences version 28.0. Obtaining patient consent was not necessary, as no patient data was used in this study.

RESULTS

Three thousand four hundred and ninety-one adverse events involving the FS laser system were reported from January 2012 to April 2022. Of these, a total of 2355 entries were removed. 1136 entries met the inclusion criteria and were further analyzed [Figure 1].

Figure 1 Flowchart of reports meeting inclusion criteria. PRK: Photorefractive keratectomy

The most frequently reported intraoperative complications were incomplete cut (486 cases; 42.8%), thinner than intended flap (200 cases; 17.6%), and difficulty lifting the flap (136 cases; 12.0%). FS-related complications included opaque bubble layer (26 cases; 2.3%), air bubbles in the anterior chamber (27 cases; 2.4%), and vertical gas breakthrough (47 cases; 4.1%). Other intraoperative complications included suction loss (116 cases; 10.2%), laser malfunction (23 cases; 2.0%), and difficulty docking (27 cases; 2.4%).

The most common postoperative complications were diffuse lamellar keratitis (DLK) (88 cases; 7.8%), rainbow glare (52 cases; 4.6%), and residual refractive error (14 cases; 1.5%). Of the residual refractive error cases, 10 were due to astigmatism, three were due to undercorrection, one was due to overcorrection, and three did not specify. Table 1 contains a complete list of complications.

Table 1 Intraoperative and postoperative complications of femtosecond-assisted laser-assisted in situ keratomileusis reported to manufacturer and user facility device experience database by complication type

Complication category	n (%)	
Intraoperative		
 Dissection-related		
  Incomplete cut	486 (42.78)	
  Cut not at the same level	1 (0.09)	
  Cut too deep	3 (0.26)	
  No cut made	22 (1.93)	
  Incorrect side-cut position	1 (0.08)	
  Side-cut not smooth	2 (0.18)	
  Whitening at side-cut	4 (0.35)	
 Flap-related		
  Decentered flap	11 (0.97)	
  Thin flap	200 (17.61)	
  Thick flap	76 (6.69)	
  Small flap	2 (0.18)	
  Irregular flap, unspecified	52 (4.58)	
  Asymmetric flap	10 (0.88)	
  Uneven flap bed	11 (0.97)	
  Tear of the flap when created	10 (0.88)	
 FS laser-related		
  Vertical gas breakthrough	47 (4.14)	
  Opaque bubble layer	26 (2.29)	
  Air bubble in the anterior chamber	27 (2.38)	
 Lifting-related		
  Difficult to lift	136 (11.97)	
  Unable to lift	80 (7.04)	
  Tear with lifting	40 (3.52)	
  Sticky bed	43 (3.79)	
  Adhesions	23 (2.02)	
  Irregular stromal bed	10 (0.88)	
  Resistance	3 (0.26)	
 Other		
  Suction loss	116 (10.21)	
  Fluid or blood present	3 (0.26)	
  Unintended gantry movement	1 (0.09)	
  Laser malfunction	23 (2.02)	
  Difficulty docking	27 (2.38)	
  System error message	13 (1.14)	
Postoperative		
 Flap related		
  Flap striae	9 (0.79)	
 Interface related		
  DLK	88 (7.75)	
  Superficial punctate keratitis	4 (0.35)	
  Interface haze	12 (1.06)	
 Late-onset		
  Epithelial ingrowth	11 (0.97)	
  Corneal ectasia	1 (0.09)	
  Corneal texture changes	4 (0.35)	
 Other		
  Residual refractive error	14 (1.49)	
  Dry eye	9 (0.79)	
  Rainbow glare	52 (4.58)	
  Posterior vitreous detachment	2 (0.18)	
  Halos	11 (0.97)	
  Starburst glare	3 (0.26)	
  Floaters	2 (0.18)	
Total	1136	
MAUDE: Manufacturer and user facility device experience database, FS-LASIK: Femtosecond laser-assisted in situ keratomileusis, DLK: Diffuse lamellar keratitis, FS: Femtosecond

A majority of the reported cases were done using the brands LensX (Alcon Laboratories, Inc.) and WaveLight FS200 (Alcon Laboratories, Inc.), with 735 and 372 cases, respectively. Other brands included Intralase (8 cases), Femto LDV (6 cases), and Ziemer (4 cases). Interestingly, 303 of the WaveLight FS200 cases were reported in 2015, which contributed to the high number of reported cases that year. The number of cases reported per year is depicted in Figure 2.

Figure 2 Number of femtosecond laser-assisted in situ keratomileusis reports made to manufacturer and user facility device experience database by year

Of the 672 cases in which the outcomes were reported, 476 were successfully completed and 196 were aborted. Among completed cases, 236 were completed with manual dissection. Among aborted cases, 53 were converted to photorefractive keratectomy. The most common reasons for aborting a case were uncut flap (79 cases), suction loss (59 cases), inability to lift the flap (42 cases), button-hole defect (11 cases), and thin flap (10 cases). The number of aborted cases and reasons for aborting are reported in Table 2.

Table 2 Case outcomes and reasons for aborting cases

Case outcomes	n (%)	
Aborted cases	196 (17.25)	
 Aborted and converted to photorefractive keratectomy	53 (4.67)	
Completed cases	476 (41.90)	
 Completed with manual dissection	236 (20.77)	
Unknown	300 (26.41)	
Case aborted reason		
 Suction loss	59 (5.19)	
 Uncut flap	79 (6.95)	
 Tear when lifting	2 (0.18)	
 Unable to lift	42 (3.70)	
 Button hole defect	11 (0.97)	
 Opaque bubble layer	5 (0.44)	
 Laser issue	6 (0.53)	
 Unable to clear error message	2 (0.18)	
 Thin flap	10 (0.88)	

DISCUSSION

Although various reports have studied FS-LASIK outcomes and adverse events, no prior studies have analyzed them using the MAUDE database. Incorporating both mandatory and self-reported outcomes from ophthalmologists and patients allows for the MAUDE database to serve as a repository for rare and less commonly reported adverse events that are not typically found in clinical trials with narrower inclusion criteria.

Our study found that between 2012 and 2022, the number of adverse events reported in the MAUDE database peaked in 2015 (363 events) and progressively declined until 2020 (66 events), before rebounding in 2021 (126 events). Given the continual growth in estimated LASIK procedures over the past decade, the decline in adverse event reports from 2015 to 2020 is likely not attributed to changes in number of surgeries performed.9 One hypothesis for the decline in adverse events may be accredited to the collective experience, training, and comfort level of surgeons as a whole, with innovations in treatment algorithms and a larger database of nomograms to derive treatment plans. Furthermore, as medical devices become less novel, mandatory reporting policies may become less stringent and the inclination to self-report adverse events (particularly for nonmandatory reporters) may decline, attributing in part to the decline in reported adverse events.

Of note, a large proportion of the adverse events reported in 2015 were from the Wavelight FS200 FS laser system (79.4%). We were unable to find a credible explanation for what may have led to the large number of cases in that year. Despite the rise in adverse events reported from the Wavelight FS200 laser in 2015, it is important to note that these findings do not indicate comparative efficacy or safety, with all FS laser systems having previously been shown to be predictable and safe for making corneal flaps in LASIK.10

Generally, the overall complication rates with both MMK and FS-LASIK are low, with several studies reporting adverse events in <1.0% of cases.1112 One retrospective study of over 84,000 LASIK operations found the incidence of partial flaps, thin/irregular flaps, and free flaps to be 0.1%, 0.07%, and 0.01%, respectively.12 Our study found that the most common intraoperative complications reported in the MAUDE database were related to flap creation. These complications were similar to those reported in MMK LASIK, such as unintended flap thickness, incomplete flaps, free caps, and buttonholes.11 Despite shared complications, there are notable advantages and disadvantages of FS-LASIK that can affect the incidence rates of complications.

One advantage of FS-LASIK compared to MMK LASIK is the improved postoperative flap adhesion, with one study of 81,238 LASIK procedures reporting a lower incidence of flap displacements through FS laser (0.003%) compared to MMK (0.033%).13 This has been hypothesized to be attributed to differences in MMK flap thickness, particularly in hyperopes, which results in heavier flaps that can create increased rotational forces about the horizontal axis which may destabilize the flap.13 In addition, increased stability has typically been found in the superior hinges derived from FS-LASIK, as opposed to nasal hinges from translational MMK.11 In addition, Kim et al. demonstrated that FS laser produces greater inflammation and subsequently stronger postoperative flap adhesion.14 This advantage is corroborated in our MAUDE database analysis, which contained limited flap dislocations following FS-LASIK between 2012 and 2022. Another advantage of the FS laser over MMK is a lower incidence of epithelial ingrowth between the corneal flap and stromal bed following LASIK.151617 Higher rates of epithelial ingrowth are thought to occur with the microkeratome because it creates a more oblique incision at the flap margin that creates a greater surface area of incision into the epithelium, which results in greater injury to the epithelial cells and release of cytokines involved in epithelial healing and proliferation. In comparison, the incision in FS-LASIK creates a more vertical cut, promoting better adherence of the flap to the stromal bed, and sealing the entry of epithelial cells from entering through the flap.18 Only 11 adverse event reports in the MAUDE database included epithelial ingrowth.

While there are advantages of FS-LASIK that seem to decrease the frequency of certain complications, there are also unique complications that may arise as a result of the use of the FS laser, such as rainbow glare, epithelial gas breakthrough, and opaque bubble layer formation.1 These unique FS-LASIK complications accounted for 125 of the adverse events reported in the MAUDE database. Rainbow glare is a result of constructive interference from FS laser spots, with one study showing no relationship with age, gender, or refractive error, but a positive association with the level of laser energy used during FS-LASIK.19 Similarly, gas bubbles may appear as a result of the FS laser, with vertical gas breakthrough occurring between the dissection plane and subepithelial space, or opaque bubble layers forming at the stromal interface resulting in transient opacity. One study reported an opaque bubble layer incidence rate of 48%, although the average area affected was <10% of the flap area.20 Recent development of IntraLase lasers that require lower energy settings have been associated with decreased incidence of DLK, opaque bubble layer, and transient light sensitivity.21 It is important to take into consideration that surgeons may have a predilection to report these novel findings over other common LASIK complications, due to their unique nature as complications not previously seen with MMK.

Despite the potential for unique complications that may arise from FS-LASIK, the most commonly reported intraoperative complications were flap related, which have been commonly documented with MMK LASIK as well.11 During FS-LASIK, an incomplete flap can occur due to suction loss or FS laser malfunction, which may occur during the raster pattern and before the side cut is initiated. The risk of incomplete flaps in particular, using FS-LASIK, has been reported to be around 0.06% in one study by Haft et al., which is lower than rates reported in recent MMK studies.41122

There were several limitations to this study. First, there is no standardized policy for reporting adverse events in the MAUDE database. While some entries provided details on the outcomes of complications and whether repeat surgery was done in any of those cases, other entries did not include these details. During data collection, we only included data explicitly reported by entries and therefore, our numbers could underreport complications. It has also been noted in prior studies that the MAUDE database is subject to underreporting of adverse events.723 Similar to the prior study published looking at FLACS complications using the MAUDE database, in this study, we were also unable to draw conclusions based on any patient characteristics and device settings, which may have played a role in the adverse events.7 Unfortunately, this information is also not reported in the database. Since it is possible for anyone to report adverse events to the MAUDE database without any unique patient identifiers, there is the risk of reporting bias with potential duplicate entries. In addition, the different devices for performing FS-LASIK have all been on the market for different amounts of time, which may contribute to variation in the number of reports filed. Finally, the MAUDE database is a passive surveillance system which is not intended to be used to evaluate the rate of adverse events and therefore cannot be used to determine the incidence or prevalence of reported events. This limited our ability to run advanced statistical analyses on the data and influenced the study to be more qualitative in nature. Despite these limitations, this is the first study to report on the complications involving FS-LASIK using the MAUDE database. The findings from this study provide insight into the spectrum of complications related to FS-LASIK, including those that are rarer. It is important for ophthalmologists to be aware of all potential adverse events related to FS-LASIK to best counsel patients and prepare for any complications.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
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