An Updated Keratoconus Screening Protocol for 2022

Diagnosing patients early in their disease course is the best-case scenario in most conditions, and keratoconus is no exception. Finding keratoconic eyes before progression steals vision, so those eyes can be successfully treated with therapies such as corneal cross-linking (CXL), is the goal. But without the right equipment and knowledge of how to target and screen, patients with keratoconus (especially younger patients) can go undetected until real damage is done, research shows.¹

“You want to identify and intervene prior to permanent loss of vision,” explains Michael W. Belin, MD, a corneal specialist at Illinois Society of Eye Physicians & Surgeons in Vernon Hills, IL and an ophthalmology professor at the University of Arizona in Tucson, AZ. “Imagine if we only treated high blood pressure or high cholesterol after the first heart attack? Currently, the standard epi-off crosslinking is not without some risk, but as newer approaches become available, with a better risk/benefit ratio, earlier intervention will become standard.” 

That identification/intervention will only be more important in the future. Dr Belin cites The Raine Study, published online in 2020, which found that 1 in 84 people in an Australian population had keratoconus, one of the highest reported rates in the world.² He predicts that routine tomographic keratoconus screening for school-age children is likely to become more common as rates rise. “Obviously, any individual with a family history, children with complaints of poor vision, high astigmatism, eye rubbing, and/or frequent changes in glasses need to be evaluated,” he adds.

If keratoconus is found late, patients face more challenges from degraded vision, points out Steven A. Greenstein, MD, a corneal specialist at The Cornea and Laser Eye Institute Hersh Vision Group in Teaneck, NJ, and a clinical assistant professor at Rutgers – New Jersey Medical School in Newark, NJ. 

“The more irregular the cornea is, the harder it is to correct their vision with our standard approaches of glasses or soft contact lenses,” he says. “So, as keratoconus gets worse, we have to either use specialty contact lenses, or we have to take further surgical action, whether that be with ring segments, corneal inlays, or eventually corneal transplant to be able to correct a patient’s vision. And so, the sooner we can stabilize the disease before these things happen, the better the quality of life can be for keratoconic patients.”

This quandary is leading clinicians, Drs Belin and Greenstein included, to investigate new approaches to identifying those at highest risk for keratoconus, as early as possible. That’s going to include utilizing a screening algorithm that takes all settings (even those with less advanced technologies) into account, and a staging and classification system for modern times, respectively, plus the potential future benefits of genetic testing in these patients. 

Screening At-Risk Keratoconus Patients in Any Practice

The journey begins with asking when ophthalmologists should consider a patient suspect for keratoconus, keeping in mind that not every practice has access to advanced state-of-the-art diagnostic testing. Dr Greenstein and colleagues are attempting to answer this question, starting with their poster presentation at the American Society of Cataract and Refractive Surgery (ASCRS) 2021 meeting in Las Vegas, “Refraction and Keratometry in Keratoconus: A Proposed Screening Algorithm.”³ After surveying eyecare practices where patients receive their primary eye care, they found that many do not have access to corneal topography. 

While that’s something that will probably change over time, it remains likely thatmany optometry practices, where younger patients are often screened, will not have access to topography on a regular basis, Dr Greenstein suggests. “We tried to step back and see if there were other ways that we could identify — particularly for younger patients — who should be screened, and then referred for the next level of screening with corneal topography.”

Their retrospective analysis of 1020 keratoconus eyes using the Pentacam^® (Oculus) device found that 50% of keratoconus eyes had against-the-rule (ATR) astigmatism, and that, for participants younger than 20 years, 37% and 32% had ATR and oblique astigmatism, respectively. They concluded that patients with at least 2 D of refractive astigmatism, or with 1 D to 2 D of ATR refractive astigmatism, should be further evaluated with corneal topography, and doctors should give “additional consideration” for topography referral to patients with 2 D or more of corneal astigmatism. 

“The key take-home message from what we’ve looked at so far, is that the manifest refraction seemed to be the best early screening tool when you don’t have access to topography,” Dr Greenstein says. He and his colleagues’ next step is establishing a multi-centered prospective trial to corroborate these results.

A New Staging and Classification System for Keratoconus Screening

Many clinicians continue to rely on the most widely used system for grading keratoconus — the Amsler-Krumeich system (AK). But they might not realize just how much it has aged. Created in 1947, AK does not evaluate the posterior corneal surface. Based on keratometry and optical pachymetry, it measures only the central anterior curvature and apical thickness. It was helpful when keratoconus was treated primarily with rigid gas permeable lenses and penetrating keratoplasty; now, with more modern therapies (and refractive surgery that can lead to postrefractive surgery ectasia in undetected cases), it is no longer as helpful, according to a 2020 article composed by Dr Belin.⁴ 

A proposed replacement, the Belin ABCD staging and classification system was designed to address the more current needs in keratoconus screening, partly in response to the 2015 Consensus document published in Cornea that year.⁵ The Belin ABCD staging and classification system looks at 3 objective measurements, 2 that are machine (Pentacam) generated, and 1 subjective (vision) test. Dr Belin defines the ABCD staging/classification system as appropriate for population-based studies and the ABCD progression display as designed for following and documenting change in individual patients.⁶ 

“The Belin ABCD progression display evaluated the 3 objective parameters and determines when there has been statistically significant change. It displays both 80% and 95% confidence intervals and evaluates each parameter individually. The main clinical advantage and utilization of the display is to identify progressive change as early as possible and prior to visual loss,” he says. 

“Currently, relying solely on Kmax means that most patients have to have lost vision and that the visual loss has to progress. This is counterintuitive to what we normally do in medicine, which is to prevent sequelae, not wait until permanent deficit occurs. The Belin ABCD progression display should allow us to identify progressive change at the earliest possible period and to intervene to preserve ‘normal’ vision.”

Several peer-reviewed studies have demonstrated the ABCD progression display’s utility, he says. One recent article even found that, in patients treated with CXL based on standard Kmax change, on average, they could’ve been identified 6 months earlier with the progression display.  

“As more and more peer-reviewed papers become available, it is the hope that insurance companies will recognize the disservice of delaying treatment and relying solely on Kmax as the determinant for treatment,” he says. 

Useful Diagnostic Tools for Keratoconus Screening

While placido disk-based topography is commonly used for keratoconus screening when practices have access to it, it is an older tool that only images the anterior corneal surface, Dr Belin points out. “The earliest changes seen in ectatic disease will almost always show up first on the posterior surface and so standard anterior topography is limited,” he says. 

In contrast, corneal tomography, like with the Pentacam system (which uses a Scheimpflug camera) gives doctors anterior and posterior topographic, pachymetric, and aberrometry maps.⁷ One study in the International Journal of Ophthalmology compared placido disk-based topography to high-resolution rotating Scheimpflug camera in keratoconic and post-LASIK eyes, and found that that the Scheimpflug camera provided more repeatable and reproducible measurements of Ks, Kf, and Ks.⁸

But placido disk-based topography should not be ruled out just yet, thinks David Hardten, MD, founding partner of Minnesota Eye Consultants in Bloomington, MN. The main reason: It’s affordable. In his own practice, clinicians use tomography for keratoconus screening and then for follow-up — especially if patients have severe disease in 1 eye but not the other and need close follow-up, but many practices don’t have advanced tomography, and placido topography can still be very useful.

As for anterior-segment optical coherence tomography (AS-OCT), a high-resolution cross-sectional imaging modality created for retinal imaging, there’s a lot of similarities between it and Scheimpflug-based tomography, Dr Belin says, but currently, the screening software on the Scheimpflug devices are more specific for keratoconus screening and detection. 

OCT has been incredibly helpful in providing information not just about the shape of the entire cornea but also changes in the epithelial thickness, Dr Greenstein says.

“Epithelial thickness maps have also been shown to potentially identify early cases of keratoconus and early irregularity because, in keratoconus, the epithelium tends to thin over the steepest portions of the cornea over the cone and thicken around the edges of the cone to try to smooth out the corneal surface, and if we can identify those changes early, we can also use that to help us in identifying keratoconus,” he says.

Genetic Testing For Early Keratoconus Detection

Another option working gaining steam is genetic testing to early keratoconus detection. It’s known that the disease has a genetic component, Dr Hardten points out, with whole biological families sometimes sharing the condition.⁹ In his practice, they’re using AvaGenTM (Avellino Lab USA, Inc.), the first genetic test to determine risk for keratoconus and other corneal dystrophies, which launched in 2021.¹⁰ The test involves a simple cheek swab andcan be used in young children who might not be the best candidates for screening imaging. Dr Hardten adds that past methods of screening/detection are not likely disappear anytime soon: For example, “for a 45-year-old who doesn’t have any children and wants to know if they have keratoconus, then topography, or tomography, is much more useful than genetic testing.”

Dr Greenstein and his colleagues will be working with Avellino on keratoconus and corneal ectasia modeling, and are excited to use the company’s genetic test for keratoconus. The most common questions that keratoconus patients with kids have been asking for years are “How likely is it that my kid is going to have this?” Another common question is, “Should we screen our children for keratoconus?”

“Right now, our best answer is that we tell them to bring them in, at a relatively young age, around 10 years old, and we’ll start to do corneal topography for them. And based on what we see, and based on how much astigmatism they have in their refraction and on their cornea, we’ll monitor them over time. But with genetic testing, we hopefully will be able to discuss with those families a risk score, for example your child has a high risk for keratoconus or low risk for keratoconus.”

That’s a potential game changer in keratoconus screening for young children, he says, because it could help eliminate unnecessary imaging for those at low risk, while giving ophthalmologists more clues about whom to carefully monitor, like those at higher risk.

References

1. Kreps EO, Claerhout I, Koppen C. Diagnostic patterns in keratoconus. Cont Lens Anterior Eye. 2021;44(3):101333. doi:10.1016/j.clae.2020.05.002
2. Chan E, Chong EW, Lingham G, et al. Prevalence of keratoconus based on Scheimpflug imaging: The Raine Study. Ophthalmol. 2021;128(4):515-521. doi:10.1016/j.ophtha.2020.08.020.
3. Greenstein S, Wawrzusin P, Hersh P, Gelles J, Ando A, Garvey N. Refraction and keratometry in keratoconus: a proposed screening algorithm. Poster presented at: 2021 ASCRS Annual Meeting; July 2021; Las Vegas, NV. Abstract 76244.
4. Gomes JA, Tan D, Rapuano CJ, et al. Global consensus on keratoconus and ectatic diseases. Cornea. 2015;34:359–369. doi:10.1097/ICO.0000000000000408
5. Belin MW, Kundu G, Shetty N, Gupta K, Mullick R, Thakur P. ABCD: a new classification for keratoconus. Indian J Ophthalmol. 2020;68(12):2831-2834. doi:10.4103/ijo.IJO_2078_20.
6. Belin MW, Jang HS, Borgstrom M. Keratoconus: diagnosis and staging. Cornea. 2022;41(1):1-11. doi:10.1097/ICO.0000000000002781
7. Castro-Luna G, Pérez-Rueda A. A predictive model for early diagnosis of keratoconus. BMC Ophthalmol. 2020;20(1):263. doi:10.1186/s12886-020-01531-9
8. Penna RR, de Sanctis U, Catalano M, Brusasco L, Grignolo FM. Placido disk-based topography versus high-resolution rotating Scheimpflug camera for corneal power measurements in keratoconic and post-LASIK eyes: reliability and agreement. Int J Ophthalmol. 2017;10(3):453-460. doi:10.18240/ijo.2017.03.20
9. Bykhovskaya Y, Rabinowitz YS. Update on the genetics of keratoconus. Exp Eye Res. 2021;202:108398. doi: 10.1016/j.exer.2020.108398
10. Avellino Launches AvaGen Nationwide as First Genetic Test to Quantify Keratoconus Risk and Presence of Corneal Dystrophies. BusinessWire. https://www.businesswire.com/news/home/20210602005304/en. Published June 2, 2021. Accessed January 6, 2022.