Advancements in Ectasia Screening for Refractive Surgery

Departing from the era of radial keratotomy and conductive keratoplasty, laser-based corneal refractive procedures – LASIK (laser-assisted in situ keratomileusis), SMILE (small incision lenticular extraction) or LALEX (laser-assisted lenticular extraction) – stand among the most successful medical procedures, with very high satisfaction rates. Additionally, lens-based surgery options such as phakic implantable collamer lens (ICL) implants and lens replacement surgery, are seeing similar levels of success with increased experience and improved lens technology.

In researching evidence on outcomes of laser-based refractive surgery, I came across two pivotal articles. The Solomon review¹ published in 2016, analysed 97 articles on LASIK published between 2008 and 2015, incorporating data from 67,893 eyes. The analysis revealed that 99.5% of patients attained a visual acuity of at least 20/40 or better following the procedure. The overall incidence of a loss of two or more lines of corrected distance visual acuity (CDVA) was minimal, affecting only 0.61% of eyes. Impressively, patient satisfaction rates were notably high, with 98.8% expressing satisfaction with LASIK during the specified period.

Similarly, Tanzer et al.² focussed on the outcomes of LASIK, specifically among naval aviators, a group with exceptionally high visual acuity demands. Involving over 600 eyes, primarily with myopia, the study found that 98.3% of myopic and mixed astigmatism eyes achieved a 6/6 or 20/20 result post-procedure. Additionally, approximately 40% of myopic and mixed myopic eyes experienced an improvement of at least one line of corrected Snellen acuity, while 95.7% of hyperopes achieved 6/6 (20/20) vision. Impressively, 95.6% of pilots perceived LASIK to have enhanced their effectiveness as naval aviators, with an overwhelming 99.6% indicating willingness to recommend it to others.

These findings underscore the safety and efficacy of LASIK, even in professions with the most demanding visual requirements, and the ability of refractive surgery to deliver results where there is a need for high precision.

A patient scheduled for laser treatment in 2024 can expect enhanced precision and better outcomes due to the advancements in laser technology achieved through numerous innovations in recent years. We no longer just treat the patient’s refraction but optimise their treatment via customised treatment profiles such as aberration free, topography-guided, customwavefront, and more recently, ray tracing. Patients also benefit from a markedly more comfortable procedure due to faster lasers and decreased suction pressure from femtosecond lasers compared to the microkeratome. They often remark on how much smoother the experience was than they had anticipated. This is particularly true for SMILE Pro, my procedure of choice for myopic treatments, with 10 second laser treatment times, a faster workflow, no smell, and a small incision, which means less post-operative dry eye.

SCREENING FOR CORNEAL REFRACTIVE SURGERY

The success of refractive surgery depends heavily on meticulous patient selection and screening processes. Factors affecting selection include: the patient’s refraction; their ocular health, especially ocular surface and dry eye; ocular anatomy e.g. corneal shape, corneal diameter and thickness and anterior chamber depth; medication use (especially those associated with dry eye); medical and psychological history; and genetic risks.

One of the most critical aspects of screening is the assessment for the risk of post-operative corneal ectasia. Although the general prevalence of post-LASIK ectasia is unknown, there are several reports that show a prevalence rate varying from 0.02% to 0.6%.^3,4 Corneal thickness and the level of myopia remain preliminary measures in assessing patient suitability for laser surgery in the community setting. It is important to note that currently SMILE or lenticule-based procedures and LASIK are considered equivalent in terms of post-operative ectasia risk.

In 2003 Randleman et al. published a comparative analysis between uneventful LASIK patients and those developing corneal ectasia post-LASIK.⁵ Their findings revealed significant distinctions between the two groups. Patients who developed ectasia were characterised by:

1. Abnormal preoperative corneal topography,
2. Younger age,
3. Higher myopia (over eight diopters of mean refractive spherical equivalent),
4. Thinner corneas prior to surgery (with a mean of 521 microns), and
5. Reduced residual stromal bed (RSB) thickness (averaging 256 microns).

Logistic regression analysis underscored abnormal topography as the most pivotal factor distinguishing between cases and controls. Subsequently, they proposed the Ectasia Risk Scoring System (ERSS), which assigns a score ranging from zero to four to each of these factors with the highest score for abnormal preoperative topography.⁶

Figure 2 shows schematic patterns of corneas at risk of subclinical keratoconus, as based on anterior corneal placido imaging published by Rabinowitz et al. in 1989, which remains very current.^7,8

While this scoring system provides a useful framework for pre-operative screening, its application remains a subject of contention. A study by Ambrósio et al. evaluated the ability of ERSS vs BAD-D methods (the BelinAmbrosio Enhanced Ectasia Display (BAD) analyses several corneal parameters to provide a ‘D value’ (BAD-D)) to predict ectasia risk among LASIK candidates and found that the ERSS failed to detect ectasia risk in 47.8% of post-LASIK ectasia cases.⁹ This is because the ERSS depended on the subjective classification of corneal topography curvature maps, which may vary tremendously among different experts. Additionally, ERSS did not specifically consider posterior corneal elevation. It did, however, emphasise the importance of evaluating topography.

In recent years, newer parameters have significantly enhanced the precision and reliability of ectasia screening. These are:

1) Corneal tomography,

2) Corneal biomechanics, and

3) Corneal epithelium as a measure for early keratoconus.

The Global Consensus on Keratoconus and Ectatic Diseases, published in the journal Cornea in 2015, highlighted posterior corneal abnormalities as the sine qua non of early ectasia. It states: “Posterior corneal elevation abnormalities must be present to diagnose mild or subclinical keratoconus.”¹⁰

Much of the current diagnostic imaging performed when screening patients for suitability of laser refractive surgery is focussed on detecting early posterior corneal elevation changes. By combining this with what we understand about the anterior cornea, advanced diagnostics have reduced the need for subjective interpretation.

It is important to mention here that eye rubbing is emerging as a risk factor that could explain the ectasia occurrence in some cases without other identified risk factors,¹¹ and is something we should all counsel our patients about. Genetic screening, such as AvaGen, continues to be developed to assess the genetic risk, but is not discerning enough yet. A positive family history of keratoconus could be used as an indicator of genetic risk with studies quoting up to 6–23.5% of keratoconus patients having a positive family history.¹²

CORNEAL TOMOGRAPHY

Corneal tomography provides threedimensional imaging of the cornea for a more detailed analysis. It is used for the characterisation of the elevation of the front and back surfaces of the cornea, along with pachymetric mapping. One notable technology in this regard is the Scheimpflug imaging system used by the Pentacam (Oculus, Wetzlar, Germany). The Pentacam was the first instrument to use a rotational Scheimpflug camera to provide three-dimensional, noncontact imaging of the anterior segment. The instrument uses a 475 nm blue light source and two camera systems to capture an image. The rotational Scheimpflug camera takes up to 50 cross-sectional images on an angle from zero to 180° in a single scan, acquiring 25,000 data points in approximately two seconds. This allows for the assessment of corneal thickness distribution, elevation, and curvature. Other excellent Scheimpflug systems, like the Galilei (Ziemer, Biel, Switzerland), and Sirius (Costruzione Strumenti Oftalmici, Florence, Italy) provide similar data and accuracy,¹³ but it would be fair to say that the Pentacam is the most studied with well-established indices that remain the current ‘gold standard’ for ectasia screening in Australia.

When identifying keratoconus, the steepest part of the cornea on the curvature map should closely align with the most elevated and thinnest part of the cornea. The Pentacam provides a ‘refractive display’, which allows for viewing these parameters together (Figure 3).

Built into the Pentacam software is the BelinAmbrosio Enhanced Ectasia Display (BAD), which provides a BAD-D to identify patients suspicious for keratoconus, who would be less suitable for laser-based refractive surgery (Figure 4). Studies have found BAD-D to have a significantly higher accuracy with sensitivity ranging from 60–95% and specificity ranging from 73–94% in various studies.^13-19

The BAD-D parameters are:

• Df: Deviation from the mean of front elevation difference map,
• Db: Deviation from the mean of back elevation difference map,
• Dp: Deviation from the mean of average pachymetric progression,
• Dt: Deviation from the mean of minimum thickness, and
• Da: Deviation from the mean of ARTmax (Ambrosio relational thickness).

A final ‘D’ is calculated based on a regression analysis that weights differently each parameter and compares against a standard database of normal and keratoconic corneas. The combined D of yellow is considered suspicious, i.e. when it is C1.6 standard deviations (SD) from the mean. Red is abnormal or frank keratoconus i.e. when it is C2.6 or more SD from the mean. Values below 1.6 D are reported in white and are viewed as within the normal range.

Understanding the various parameters presented, and applying them to each case, does require personal expertise and experience. This is because there are instances where the test will flag false positives and false negatives, which need to be evaluated in the context of all the diagnostics on that patient. For example, patients with Fuchs’ dystrophy or hypermetropic refractive error with smaller corneas can present as ‘red’ on the BAD-D analysis.

Additionally, the patient’s age can determine whether the exact value of BAD-D is suspicious. Dr Michael Belin, one of the two experts who primarily developed the BAD-D analysis, has suggested that the upper limit of the BAD might be more liberal (up to 2.2) in patients older than 40 years old who have a lower risk of ectasia.²¹

Needless to say, the BAD-D analysis is one of the most widely relied upon parameters by most refractive surgeons in screening patients for refractive surgery.

BIOMECHANICAL ANALYSIS

Understanding the biomechanical properties of the cornea is crucial in predicting its stability after refractive surgery. Corneal hysteresis, a measure of the cornea’s ability to absorb and dissipate energy, has gained significance in glaucoma management, but also ectasia screening. A lower corneal hysteresis may indicate reduced corneal resistance and increased susceptibility to ectasia.

Advanced devices, such as the Corvis ST (Oculus Optik-geräte GmbH, Wetzlar, Germany), assess corneal hysteresis and provide valuable information about the cornea’s biomechanical integrity. The Corvis ST aggregates noncontact tonometry with a very high-speed Scheimpflug camera to monitor corneal deformation. One hundred and forty images are taken within 31 seconds of the air puff to provide data on corneal stiffness.

The Corvis ST Corneal Biomechanical Index (CBI) was described by Vinciguerra et al. in 201622 as an objective index to detect keratoconus. Previous studies examining the specificity of corneal hysteresis in eyes suspected of keratoconus did not establish a strong correlation with high specificity for predicting the risk of ectasia.^23,24

However, a further study of the CBI combined with Pentacam tomographic data (as provided by the BAD-D analysis), and using AI models, now shows superiority of this metric rather than CBI or BAD-D alone. This metric is known as the Tomographic Biomechanical Index (TBI). It integrates the data from the Corvis ST and Pentacam into a value from zero to one, with values ranging from 0.35 to 0.75 representing suspicious corneas with moderate risk of ectasia, while values over 0.75 have a high risk for corneal ectasia. TBI provides high sensitivity and specificity and, in one seminal study, an area under the curve (AUC) of up to 0.985 (Figure 6).²⁵

It is important to remember that when screening patients for refractive surgery we are not only screening for forme fruste keratoconus but those corneas that are susceptible to ectasia should they undergo the biomechanical change that corneal refractive surgery induces. This is where corneal hysteresis is a useful parameter.

Figure 7 demonstrates an example of one of my patients with suspicious inferior steepening and a pattern of pellucid-marginal degeneration (PMD) on topography, where the BAD-D was normal but corneal hysteresis and TBI were not. This helped to objectively stratify that patient into someone with a higher risk for post-LASIK ectasia. In this instance the patient was presbyopic and even though he had a lower risk of post-LASIK ectasia as per his age, he was offered lens-based surgery.

When corneal biomechanics are considered, age becomes a lesser factor as age is only a pseudo-measure of biomechanics with the understanding that older patients have stiffer corneas.

RESIDUAL STROMA BED AND PER CENT TISSUE ALTERED

It seems appropriate to discuss residual stroma bed (RSB) and per cent tissue altered (PTA) in the context of corneal biomechanics. It is intuitive that the thinner the intact residual stroma, the more biomechanically weak a cornea is. The key is to identify the critical level at which the cornea is biomechanically weak enough. This may not be the same for all patients, but some guidelines have been helpful. As mentioned earlier, a RSB of 250 µm was considered safe for patients undergoing corneal refractive surgery, but more recently 300 µm is considered safer for LASIK,²⁶ while SMILE may allow a lesser RSB of 250 µm as the minimal RSB due to a biomechanically stronger anterior cornea.

Some studies suggested that PTA could be used to predict ectasia risk.

The equation for PTA is: PTA = (FT + AD) / CCT, where PTA is per cent tissue altered, FT is flap thickness, AD is ablation depth, and CCT is preoperative central corneal thickness.

Previously, a PTA of >40% was considered an independent risk factor for ectasia following LASIK.27 More recently, Ong et al. suggested that the PTA can be extended in SMILE without impacting safety.²⁸ There are a range of potential explanations for this variation between LASIK and SMILE.^29,30 Firstly, cohesive tensile strength appears greater in the anterior stroma lamellae than the posterior stromal lamellae.²⁹ Secondly, Sinha et al. suggested that the LASIK flap essentially decouples the anterior cornea from its anchoring boundaries unlike SMILE, which mostly preserves anterior stromal structure.²⁹ The difference, however, is not permanent with subsequent wound healing around the LASIK flap, as reported by Khamar et al.³¹

The usefulness of PTA has not been substantiated by further studies^32,33 but provides a useful framework or pseudo-measure of the amount of myopia being treated and hence its effect on corneal biomechanics.

EPITHELIAL THICKNESS MAPPING

Epithelial thickness mapping has emerged as a valuable tool in the screening process for ectasia risk as established by Professor Dan Reinstein, based on his high-frequency ultrasound studies.³⁴ This technique involves mapping the thickness of the corneal epithelium as an independent measure of posterior corneal elevation.³⁵

Epithelium can be considered a ‘masking agent’, covering abnormalities i.e., the ‘peaks and troughs’ of the stroma to allow a smooth anterior corneal surface. In patients with corneal scarring, we note a thicker epithelium over a depressed corneal scar. Conversely in patients with keratoconus, an early thinning of the epithelium over the cone can be detected. A characteristic pattern, known as the ‘donut pattern’ of epithelial remodelling, is observed. This pattern manifests as central epithelial thinning surrounded by a ring of epithelial thickening. Some studies would suggest a difference of more than six microns³⁶ between the thin and thick cornea is abnormal. By detecting this distinctive epithelial morphology, clinicians can identify subtle corneal changes indicative of early-stage keratoconus.

Incorporating epithelial thickness mapping into ectasia screening protocols enhances the ability to detect corneal abnormalities at an early stage. Figure 9 shows an example of a patient with asymmetrical keratoconus with marked thinning of epithelium in the eye with an advanced cone, where the thinner corneal epithelium is surrounded by an almost continuous annulus of thicker epithelium. There is a lesser but similar pattern of epithelial change in the forme fruste right eye as well.

When it comes to evaluating epithelial thickness maps, certain ocular conditions can affect the results. These include anterior basement membrane dystrophy (ABMD), which can cause an irregular epithelial profile; dry eye that can lead to changes in epithelial thickness; and eyelid anatomy differences that can lead to changes in epithelial thickness (e.g. ptosis causes superior thinning, which can create apparent inferior steepening on topography).

As with any measurement device, there is also the possibility of measurement error. With epithelial mapping, the main source of error is the reliability of the algorithm for detecting Bowman’s layer on the B-scans.

Several platforms exist for epithelial mapping. Cirrus optical coherence tomography (OCT) (ZEISS, Germany), Anterion (Heidelberg, Germany), Avanti (Visionix, USA) and, CSO MS39 (CSO, Italy). I use the MS-39 AS-OCT. Its notable advantage lies in its integration of Placido disc topography and high-resolution SD-OCT-based tomography, offering a comprehensive assessment of the cornea including epithelial thickness, corneal curvature, elevations, pachymetry, and corneal diopteric power. Additionally, its aberrometric analysis provides a thorough evaluation of corneal aberrations. In approximately one second, the scanning process acquires one placido top-view image and a series of 25 spectral-domain-OCT radial scans at a wavelength of 840 nm, with an axial resolution of 3.6 µm (in tissue), a transverse resolution of 35 µm (in air).³⁷ It measures 31,232 points on the anterior surface and 25,600 on the posterior surface, together with high-speed scanning of 30,000 A-scans per second.³⁸

The epithelial interface is fainter when using OCT devices with variability between devices. The epithelial thickness from the Cirrus is often significantly thinner than the other devices and the maps more irregular.

This might make the measurement less reliable when examining for subtle amounts of change in screening for ectasia. The MS39 provides higher resolution scans, and also a ‘keratoconus screening report’ based on several key corneal indices to produce an enhanced screening tool for keratoconus (Figure 10).³⁹

There may be a movement towards OCT-based imaging for ectasia screening. As Scheimpflug systems employ 470–475 nm wavelength light, they are sensitive to corneal opacities, resulting in hyperreflective images of an inaccurate contour.⁴⁰ Due to total internal reflection in the peripheral cornea, direct visualisation of the anterior chamber angle is not possible and hence derived by extrapolating the data. The OCT however, uses longer wavelength infrared light, which results in higher resolution images. In addition to epithelial thickness mapping, the MS39 is a very useful anterior segment OCT, which allows imaging of LASIK flaps, SMILE interface, implantable collamer lens placement and vault, and angular structures. Currently however, the robustly evaluated algorithms of the BAD-D and TBI are not available on any OCT-based devices.

ARTIFICIAL INTELLIGENCE AND MULTIMODAL IMAGING

It is apparent to most refractive surgeons that in the present time, using one device for ectasia screening may not be sufficient or sensitive enough. Using multiple modes of imaging to further evaluate and substantiate suspicious abnormal corneas is important. In addition to improving sensitivity, this will minimise false positive and false negatives, which each mode of imaging is subject to.

The integration of artificial intelligence (AI) and machine learning (ML) algorithms will further revolutionise ectasia screening. These technologies analyse vast datasets of corneal characteristics and outcomes, identifying patterns and correlations that may not be apparent to the human eye. Ultimately, being able to ‘plug’ all available parameters into an AIbased screening tool will enhance the accuracy of ectasia risk assessment by considering multiple factors simultaneously. This has already been achieved with the BAD-D and TBI analysis,⁴¹ and in a model with epithelial thickness mapping and Pentacam indices.⁴² Others models are under development (sys. braincornea.com). Once standardised, this will likely represent the new holy grail.

CLINICAL DECISION SUPPORT SYSTEMS

The integration of advanced screening technologies has paved the way for the development of clinical decision support systems (CDSS) in refractive surgery. CDSS combines clinical expertise with data-driven insights to assist surgeons in making wellinformed decisions tailored to each patient’s unique characteristics. This is already available for cataract surgery and lens patients (ZEISS Veracity) but remains in development for purposes of ectasia risk screening.

My current standard procedure for refractive patients involves conducting all the abovementioned comprehensive screening assessments and analysing the outcomes in conjunction with the patient’s refraction, ocular anatomy and any other specific variables. Subsequently, I offer a conclusive recommendation to the patient regarding their available choices and the most suitable procedure.

ALTERNATIVE OPTIONS

For patients with forme fruste/suspicious cornea, and hence considered ineligible for laser-based procedures, alternative solutions include phakic implantable lenses like the STAAR Visian ICL and, for presbyopic patients, custom lens replacement or refractive lens exchange with presbyopia correcting IOLs (PC-IOLs). Once again, patient suitability must be determined, with regards to available anterior chamber depth, sulcus length, and other specific requirements. Ultimately, the decision rests with the consulting surgeon.

Phakic ICL lens-based procedures have several advantages which include:

1. Preservation of the corneal anatomy and minimal induced aberration,
2. Correction of large levels of ametropia including astigmatism without putting the cornea at risk of regression,
3. No impact on future biometry calculation for cataract surgery in the future, and
4. Minimal induced dry eye compared to LASIK and photorefractive keratectomy (PRK).

Some clinicians may choose PRK in instances where the cornea is suspicious for early keratoconus. While the incidence of ectasia with PRK is low, it is not zero. Hence my approach is to reserve PRK for refractive corrections where the topography is normal but corneal thickness is low for safe RSB; or patients with ABMD, which is a very small subset. I also avoid doing large levels of myopic correction with PRK and any hyperopic corrections. There are several reasons for limiting PRK in my practice. These include, longer healing times; possible PRK haze with larger levels of correction despite the use of anti-metabolites; postoperative discomfort and longer recovery; prolonged use of steroids; and regression of larger corrections.

Having said that, I do perform a limited number of cases with combined topographyguided PRK and corneal cross-linking (CXL) for cases with true keratoconus. This is quite a different proposition and something I have discussed in a previous mivision article.⁴³

Finally, there is some evidence for combining LASIK or SMILE with abbreviated CXL know as LASIK Xtra and SMILE Xtra for ‘borderline’ cases, but this is yet to be substantiated by larger, longer-term studies.^44,45

CONCLUSION

As refractive surgery continues to evolve, ectasia screening remains a cornerstone in ensuring patient safety and optimising visual outcomes. The integration of advanced technologies, such as corneal tomography, biomechanical analysis, epithelial mapping, and artificial intelligence, have significantly elevated the standards of ectasia screening. By investing time and effort in understanding the insights provided by cutting-edge technology, we not only enhance safety measures for our patients but also instil confidence within the broader community regarding refractive surgery. This confidence is pivotal in expanding access to vision correction procedures, allowing more patients to enjoy visual freedom and the associated lifestyle benefits.

Dr Aanchal Gupta is a cataract, refractive, and corneal surgeon and the owner of IVISION LASER in Adelaide. Fellowship trained in Cornea and Refractive Surgery from the University of British Columbia, Canada, she was recently awarded the fellowship to the World College of Refractive Surgery and Visual Sciences, which has been awarded to only select refractive surgeons around the world.

Dr Gupta is a RANZCO College Councillor, a Senior Clinical Lecturer at the University of Adelaide, and is the Australian and New Zealand Ambassador for the World Refractive Surgery Alliance (RSA). She is also part of the committee of management for the Australian Society of Cataract and Refractive Surgery (AUSCRS).

To earn your CPD hours from this article visit: mieducation.com/advancements-in-ectasiascreening-for-refractive-surgery.

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