Discussion
This systematic review estimated the incidence of post-refractive ectasia in PRK, LASIK, and SMILE. For clarification of reporting, “incidence” in its original statistical definition means the number of new cases of a disease per unit time, often over 1 year [
171]. However, the term incidence is used loosely in the literature to represent the occurrence of disease or the new cases observed within the time period of the investigation. The data collected in the present study also report disease occurrence rather than true incidence, though “incidence” is utilized for consistency with the literature.
In the present study, there was no difference between the frequency of ectasia in male and female patients, even though keratoconus as a whole tends to be more common in men [
172]. Of the 296 LASIK cases with a documented method of flap creation, ectasia occurred more frequently with femtosecond laser (54%) compared to microkeratome (46%), which may be due to the larger proportion of cases in this literature search occurring after introduction of the femtosecond laser. We would have expected lower rates of ectasia with femtosecond flap creation since this method is considered to make thinner and more predictable flaps [
173]. Regarding post-PRK ectasia, the higher RSB and lower PTA compared to LASIK and SMILE are likely a reflection of the larger proportion of low myopes undergoing PRK. Ectatic eyes tended to have thinner corneas preoperatively in PRK than LASIK, aligning with the use of PRK for patients with thin corneas who are not candidates for LASIK. When assessing risk factors, ERSS is a validated tool for predicting post-LASIK ectasia [
10]. Interestingly, the ERSS calculated in the present study for patients who underwent PRK and SMILE showed that many eyes were considered low risk. Newer technologies, like the Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany), attempt to fill this void in predicting preoperative risk by incorporating biomechanical studies into traditional Pentacam topography [
174,
175]. However, the data output by the Corvis ST is still not well understood, and further studies are needed to establish normal parameters before it can be a useful tool in evaluating preoperative risk.
The literature search in the present study confirms that cases of post-PRK ectasia are rare, with only 57 cases reported worldwide since 2000. Incidence of post-PRK ectasia from large case series is lacking, as only two such studies were identified [
5,
13]. These reported incidences were 0.011–0.029%, comparable to the estimated incidence of worldwide post-PRK ectasia in the present study (0.020%) in patients with no identifiable preoperative risk factors. LASIK has the most reports of post-refractive ectasia, for an estimated 1453 procedures and a worldwide incidence of 0.090%. Reports of post-LASIK ectasia in the literature range from 0.013% [
5] up to 0.935% [
6], for an average of 0.284%. Although this study’s estimated incidence falls within the range reported in the literature, it likely underestimates post-LASIK ectasia, and the large case studies in Table
4 that utilize discrete populations may be more representative of the true incidence. Post-LASIK ectasia may be more likely due to differences in postprocedural corneal tensile strength. It is estimated that the stroma only regains 2.4–28.1% of its original strength after LASIK in the central region and flap margin, respectively [
176]. This supports that the creation of a LASIK flap permanently disrupts the corneal integrity, predisposing patients to the onset or progression of ectasia.
Our calculations estimate that post-LASIK ectasia is approximately 4.5 times more likely than post-PRK ectasia in patients without identifiable preoperative risk factors. If we assume PRK volume accounts for 25% rather than 15% of LVCs in some parts of the world (536,182 PRK procedures worldwide), then the incidence of post-LASIK ectasia in patients without identifiable preoperative risk factors would be approximately eight times more likely than post-PRK ectasia. This suggests that the incidence of post-PRK ectasia may be more or less prevalent based on the frequency of procedures.
SMILE is a newer refractive surgery option; the pilot case was performed in 2007, and widespread implementation occurred between 2012 and 2016 [
177]. SMILE is believed to preserve corneal integrity because the lenticule is extracted through a small corneal incision, leaving the anterior stroma unaffected [
178]. Based on a mathematical model created by Reinstein et al., SMILE has a higher postoperative relative tensile strength than PRK and LASIK [
178]. In the present study, 19 total cases, including 11 cases without identifiable preoperative risk factors, have already been reported over the 8 years that SMILE has been in practice, with more cases likely undocumented to date. Although LASIK had an estimated incidence of ectasia approximately eight times greater than SMILE, the relative infancy of SMILE as a refractive procedure impedes validation of the claim that SMILE achieves equivalent visual outcomes without the risk of postoperative ectasia. Considering that SMILE accounts for a substantially smaller proportion of refractive surgeries than LASIK, it appears that the trajectory of post-SMILE ectasia is concerning and difficult to predict at this time. It may only be a matter of time until additional cases of post-SMILE ectasia are published.
The incidences reported in the present study reflect iatrogenic ectasia to the best of our knowledge, though not all authors report whether patients had abnormal preoperative topography. Furthermore, terms such as “suspicious topography” and “keratoconus suspect” are used loosely, and not all studies utilized the ERSS definition of “abnormal” [
10]. Regardless, this study questions whether ectasia can truly be classified as iatrogenic rather than a progression of pre-existing subclinical keratoconus. To illustrate this point, one study reports a patient who developed bilateral ectasia after unilateral LASIK [
145]. The patient had no evidence of abnormal topography or family history of ocular disease and thus was considered a good candidate for LASIK. Since he developed bilateral ectatic disease 20 months later, it seems likely the patient was predisposed to keratoconus, which emerged as a natural progression of the disease rather than a consequence of his unilateral refractive surgery. We propose that referring to post-refractive ectasia as “iatrogenic” inaccurately reflects the complexity of this disease and the multitude of preoperative factors that may be unidentified on initial surgical evaluation.
To better understand the interplay of keratoconus and post-refractive ectasia, we investigated the incidence and prevalence of keratoconus in the general population (Table
5). Reports of keratoconus in the literature fall short of representing the worldwide rates of keratoconus. Studies from Northern Europe are more readily available than other parts of the world, such as South America, where no reports were able to be obtained. However, keratoconus is a known problem in South America, as evidenced by the Violet June campaign started in Rio de Janeiro in 2018 to decrease eye rubbing [
179]. Studies that stratify by ethnic groups and geographic regions demonstrate a wide range of calculated incidences. One example is in the UK, where the reported incidence of keratoconus for Asian patients was approximately four to nine times higher than for white patients from the same region [
180‐
182]. When compared across similar studies, the incidence and prevalence of keratoconus seem to be increasing over time. For example, an incidence of 1.2 per 100,000 in 2003 and 3.8 per 100,000 in 2011 was reported in Denmark [
183]; similarly, the Asian populations increased from 20 to 32 cases per 100,000 between 1989 and 2001 [
180‐
182]. Worldwide prevalence increased from 50 per 100,000 in 1998 [
184] to 86 per 100,000 in 2019 [
185]. These studies likely under-report rates of keratoconus in the general population, as they do not capture all of the cases being treated in the private sector. However, it is important to note that increasing access to more sensitive technology may have uncovered previously undiagnosed cases. Considering that keratoconus is a spectrum of disease, it is possible that patients with keratoconus compose a larger percentage of post-refractive ectasia than what is currently documented.
There are several limitations to the present review. First, the estimated incidences in this study are limited by an absence of data reporting annual refractive procedures. Extrapolation was performed to approximate the number of cases of PRK, LASIK, and SMILE worldwide based on the ratios proposed by Joffe for US data [
8]. However, Zeiss reports that over 3 million cases of SMILE were performed in 70 countries by 2020 [
186], suggesting a higher prevalence of SMILE than the 5% accounted by the present study. Until a more transparent process of reporting refractive surgeries is developed, a truly representative number of annual cases is not achievable.
It is also imperative to have a more streamlined mechanism of reporting ectasia in order to understand the absolute incidence. In 2008, the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO) database was formed as a web-based system of reporting, though only 27,339 procedures have been documented over 10 years by 47 centers/surgeons [
187]. Similarly, the International Society of Refractive Surgery (ISRS) ectasia registry has limited data access and transparency, making it difficult for the scientific community to readily understand rates of ectasia.
Underestimation of surgical volume and underreporting of ectatic eyes may have misrepresented the incidence of post-refractive ectasia. Furthermore, manual identification of eligible publications may have missed reports of post-refractive ectasia. Additionally, true incidence cannot be calculated as many articles do not indicate the time period over which their patients were included. Utilizing a weighted average as a step in the calculation of total procedures does not account for confounding factors causing annual fluctuation in the number of surgeries being performed, including financial insecurity, economic and population growth, disease outbreaks/pandemics, political climate, and technological advances. A more dynamic approach that could capture a real-time annual refractive procedure rate would provide more representative calculations. Additionally, this study identifies a need for streamlined documentation of patient characteristics such that robust evaluations of potential preoperative ectasia risk factors can be conducted.
Acknowledgements
Special thanks to: Anisha N. Somani, James Barnes, Uma Vaidyanathan, Grant Hopping, Ayesha Patil, MacGregor Hall, Alex Villarreal, Preston Baker