Kamran M. Riaz, MD, a clinical associate professor and director of Medical Student Research at the Dean A. McGee Institute at the University of Oklahoma, recently discussed with Ophthalmology Times some of the latest trends in cornea treatment.
Reviewed by Kamran M. Riaz, MD
Ophthalmologists treating patients diagnosed with myriad corneal issues today have a range of options to help provide better outcomes.
Kamran M. Riaz, MD, a clinical associate professor and director of Medical Student Research at the Dean A. McGee Institute at the University of Oklahoma, discussed with Ophthalmology Times some of the latest trends in cornea treatment.
On the refractive side, Riaz pointed out that there are several new innovations for cornea specialists today.
“I think we're seeing more surgeons doing SMILE (small incision lenticular extraction) as a primary laser vision correction (LVC) procedure,” he said. “I have not done SMILE, so I cannot comment on personal experience. However, from discussions with colleagues nationally and internationally, an increasing number of SMILE procedures are performed, especially in patients with concerns for dry eye or delayed visual recovery, which can occur after LASIK or PRK, respectively.”
Riaz said he believes patients are increasingly seeking SMILE as an LVC option, a trend worth watching from the refractive side of the cornea subspecialty. Another trend is topography-guided excimer laser treatments for treating irregular corneas that previously were deemed unsuitable for LVC. For example, patients with irregular corneal surfaces or stable ectatic disease (e.g., stable keratoconus (KCN) after corneal cross-linking (CXL)) may be potential candidates for this LVC option.
“I think more surgeons now feel comfortable with topography-guided LVC in post-CXL KCN patients, especially with at least one year of topographic stability,” Riaz explained. “Some of our international colleagues have reported good results with combined CXL and topography-guided LVC as a single procedure. However, I am still nervous about this approach until we see good long-term data, especially with multi-center studies performed in the USA.”
Riaz noted that while U.S. surgeons have been routinely performing CXL since FDA approval in 2016, they are also awaiting FDA approval for epi-on crosslinking, which is already being performed in many other parts of the world.
“I know some of my colleagues in the United States that were part of epi-on CXL trials, and they have unanimously said that epi-on CXL works very well, “ Riaz explained. “Epi-on CXL would be a huge boon for many KCN patients. One of the challenges with epi-off CXL is the pain reported by patients that makes them miserable for several days after surgery. If we can save the epithelium, we may be able to save them some misery while still providing them with good clinical outcomes. Right now, I have to tell my patients to soldier through the pain for a few days for long-term gain, which I feel really bad about!”
Riaz noted that he has been doing CXL for four years at Dean McGee. More than post-CXL pain, he has seen patients develop infections after epi-off CXL because they forgot to use or improperly used antibiotic drops after the procedure.”
“I vividly recall one patient who mistakenly used his steroid drops only instead of the antibiotic drops after CXL, and he developed a terrible corneal ulcer. I think epi-on CXL can decrease infection risk,” he said.
Riaz said he would also like to see additional CXL devices available in the domestic market, including devices that can perform epi-on CXL, accelerated CXL, or even CXL at the slit-lamp through a contact lens. Such devices are available internationally, he noted.
Another issue on the radar for Riaz is watching the number of surgeons performing CXL steadily drop because of increasing costs for riboflavin and decreasing reimbursements for a very time-intensive procedure.
“The current domestic CXL climate is shameful,” Riaz said. “One company has a monopoly on riboflavin, and the costs are ridiculously high. I know of numerous colleagues in private practice that have given up performing CXL because it’s a money-losing enterprise for them. The burden has fallen to many tertiary-care and academic referral centers for patients receiving CXL. It’s a tragedy because we know CXL can save patients from needing a corneal transplant.” aid.
Refractive Options for Keratoconus Patients
Previously, corneal surgeons avoided any corneal refractive surgical procedures in KCN patients. However, some surgeons are exploring how to perform CXL for KCN stabilization while offering patients options to decrease the need for glasses or contact lenses.
“As mentioned previously, topography-guided PRK is emerging as an option for KCN patients after CXL. Another approach is to use a phakic IOL (including toric options) to treat the refractive error. A significant advantage of this approach is avoiding any surgical removal of corneal tissue, which may potentially worsen ectasia in the long term. However, the out-of-pocket costs with phakic IOLs may exclude many patients. Finally, there has been a re-emergence of intrastromal corneal ring segments (INTACS) during this golden age of CXL.”
According to Riaz, while INTACS have been used since 2000, many corneal surgeons avoided them because they did not halt the disease process.
“While corneal surgeons used INTACS to flatten KCN corneas to improve the refractive error and facilitate contact lens fitting, ultimately, we couldn’t stop the actual KCN disease process. Many surgeons felt that INTACS were not helpful in KCN eyes. Now that we have CXL with good long-term data, some surgeons have regained interest in INTACS when used judiciously with CXL. Basically, there are two schools of thought on this: the first school believes that CXL should be done first, and INTACS second; the second believes the opposite approach is better.”
Riaz said he finds himself in the latter camp.
“A meta-analysis published in Cornea in 20181 compared surgical sequences of INTACS and CXL. The best group had both procedures done on the same day, but that can be difficult to do for logistical reasons. The next best had INTACS first, followed by CXL shortly thereafter. Intuitively, it makes sense that by placing the INTACS first, we are “flattening” the cornea, and then by using CXL, we are “freezing” it from progressing. I prefer this “flatten-and-freeze” approach in my practice.”
Bowman’s membrane transplant
Riaz explained that there has been increasing interest in performing Bowman's membrane transplantation (BMT). He said it remains to be seen if it will become a mainstream option , noting that surgery and preparation of the BMT graft are difficult.
“I think if the eye banks can start preparing ready-to-implant BMT grafts like we have for endothelial keratoplasty, it would certainly be viewed more and more as a therapeutic option,” he said. “Technically, the surgery is very challenging . I am not sure how much more effective this can be compared to other treatments like CXL combined with INTACS, phakic IOLs, and/or topography-guided LVC. The BMT graft is an onlay graft that functions like an intrastromal contact lens. “
Riaz added that he is cautiously optimistic about this treatment. However, it isn’t something he has offered to patients yet as he waits to see how clinical outcomes from surgeons performing BMT fare compared to existing treatments.
“I do think there may be a role for Bowman's membrane transplantation in the near future, but as of 2023, I don’t think it’s ready for prime time,” he said.
Rho kinase inhibitors
Rho kinase inhibitors (RKIs) have been shown to improve corneal wound healing and may help endothelial regeneration. Corneal surgeons have been using RKIs to treat endothelial diseases such as Fuchs endothelial dystrophy (FECD) for several years.
“We have seen colleagues report good outcomes with RKIs for certain patient populations, such as using them with Descemet’s stripping without endothelial keratoplasty (DWEK) type of procedures for patients with FECD. Our glaucoma colleagues are also using RKIs as an ocular hypotensive agent. Given their potential for wound healing and improving retinal blood flow, we see clinicians and researchers exploring using RKIs to treat limbal stem cell deficiency and retinal vasculopathies, respectively. As a cornea specialist, I don’t want to comment much on the latter, but I think RKIs may play a role in treating other anterior segment pathologies, either as a primary or secondary treatment, in the near future.”
Riaz said many corneal surgeons are waiting for a truly revolutionary event, which would be the availability of injectable endothelial cells. He noted that studies have previously demonstrated the concept, which worked in a limited number of patients.2
Riaz said it could improve endothelial keratoplasty (DMEK/DSAEK) outcomes or even obviate the need for these surgical procedures. “We may find that injecting endothelial cells is much safer,” he said. “And the irony would be for years, we had patients lay on their back looking up at the ceiling after DMEK, and now we may end up having to follow our retina colleagues’ lead and have them look down at the floor.”
Another recent innovation is the widespread availability of preloaded DSAEK and DMEK tissue. “Many eye banks have provided excellent, easy-to-use preloaded tissue options. In my practice, I do a lot of DMEK and still some DSAEK. Preloaded tissue allows me to do these cases in about 15-20 minutes now. With some of the DMEK injector options, we don’t even have to place a suture at the time of surgery. I teach DMEK at national conferences, and one of the things I hear from my colleagues, including veteran surgeons, who attend these courses as my students is that the availability of preloaded tissue has given them the confidence to incorporate DMEK into their practices.”
In the past, surgeons would have to prepare their own tissue, and advances are making the injections much safer.
Corneal inlays, 3D printing
Riaz also addressed corneal inlays for the treatment of presbyopia.
“We may find that with further refinement, there is a role for these types of devices for the treatment of presbyopia,” he said. “I would love to see some options for patients emerge so they can be offered to them.”
Riaz added that he is somewhat skeptical because devices that have made it to the market in the past ended up being pulled off the market.
Finally, another cutting-edge advancement Riaz noted is the potential use of 3D-printed corneal tissue.
“I think a 3D printed stromal tissue contact lens could be used for crosslinking and may be made compatible for human transplantation or use as a patch graft for injuries in war zones,” Riaz said. “When human corneal tissue isn’t available, 3D-printed corneal tissue could be a viable option.”
1 Hashemi H, Alvani A, Seyedian MA, Yaseri M, Khabazkhoob M, Esfandiari H. Appropriate Sequence of Combined Intracorneal Ring Implantation and Corneal Collagen Cross-Linking in Keratoconus: A Systematic Review and Meta-Analysis. Cornea. 2018 Dec;37(12):1601-1607.
2 Numa K, Imai K, Ueno M, Kitazawa K, Tanaka H, Bush JD, Teramukai S, Okumura N, Koizumi N, Hamuro J, Sotozono C, Kinoshita S. Five-Year Follow-up of First 11 Patients Undergoing Injection of Cultured Corneal Endothelial Cells for Corneal Endothelial Failure. Ophthalmology. 2021 Apr;128(4):504-514.