April 2020


Therapeutic Refractive Corneal Surgery
Crosslinking, combo procedures for refractive outcomes in keratoconus

by Liz Hillman Editorial Co-Director

Six-month difference maps showing crosslinking alone versus concurrent topography-guided (TG) PRK and crosslinking. Both eyes improved 1 line in CDVA, while subjectively the patient noticed improvement only in his left eye, which received concurrent treatment.
Source: Luke Rebenitsch, MD

“There are differing views out there, but I personally would rather do a laser before
crosslinking than after to avoid removing too much of the tissue that has now been crosslinked.”
—Luke Rebenitsch, MD


Crosslinking, while therapeutic to stop progression of keratoconus and corneal ectasia, leaves something to be desired by patients in terms of refractive outcomes. As such, cornea specialists have been pairing it with other devices and procedures, allowing patients to get the best of both worlds: a strengthened, stable cornea and improved visual acuity.
Luke Rebenitsch, MD, shared his practice’s algorithm for adjunct treatments to crosslinking:
1. For patients with early ectasia and with CDVA close to 20/20, they do crosslinking alone.
2. If there is significant epithelial remodeling around the cone seen on epithelium mapping as well as sufficient residual stroma, they use PTK to reduce the cone, making sure to remove no more than 50 µm.
3. If there is not significant epithelial remodeling, they consider topography-guided PRK, removing no more than 50 µm.
4. If there is significant coma across the pupil and CDVA <20/40, they consider a single intrastromal ring segment or asymmetric segments.

Crosslinking alone

“The goal of crosslinking is to stabilize the corneal biomechanics in order to prevent progression of keratoconus,” said Peter Hersh, MD. “It does have the beneficial effect that there is a little bit of decrease in the cone—on average about a diopter and a half—but the goal is to stabilize the cornea.”
Dr. Rebenitsch said he recommends crosslinking for patients with confirmed keratoconus.
“As keratoconus manifests as early as your adolescent years, we are crosslinking earlier and earlier before further damage to the cornea is done,” Dr. Rebenitsch said. “Historically, it was thought that keratoconus progression slowed or even stopped later in life. We have good data to show that is not always the case, so we use age as just one factor in evaluating for crosslinking. In general, though, the earlier we can catch it the better.”
James Loden, MD, offered a similar sentiment, saying he is a little more aggressive in recommending crosslinking to patients with keratoconus. The current FDA-approved protocol requires documentation of keratoconus progression and uses an epithelium-off, 30-minute riboflavin soak, followed by 30-minute irradiation from a UV-A light using the Avedro (recently acquired by Glaukos) system. Dr. Loden, however, uses a non-FDA approved device, compounded riboflavin, and offers the procedure to patients on a cash-pay basis.
“I think the ideal time to treat a patient is when it first shows up in their teens or early 20s. That’s where I think the real emphasis needs to be, and I’m coming from the perspective that I have keratoconus. I’ve been crosslinked,” Dr. Loden said, explaining that his procedure was done with the same non-FDA approved system. “I would give anything if we had crosslinking when I was 22 years old because mine progressed to the point where I can see 20/20 with glasses but it’s blurry. Gas permeable contact lenses are uncomfortable to wear but they give crisp vision. I wish I had the opportunity to receive crosslinking back then; we could have arrested the disease process in its very early stages.”
Waiting to show progression, Dr. Loden said, is “dereliction of duty.” “It’s like saying, we don’t want to treat your cancer until you’re having a symptom from it,” Dr. Loden said, adding that almost all cases of keratoconus will progress. It’s just a question of when and how much.
Two things that Dr. Rebenitsch said have been “game changers” in decreasing pain and increasing the speed of epithelialization is doing an epi-Bowman keratectomy (EBK) for epithelium removal and using Regener-Eyes in the postoperative period. If an eye was having delayed epithelial healing, Dr. Loden said he would pull steroid drops.
“Steroids will impede corneal epithelial healing. The most important thing to prevent a haze reaction, whether it’s with PRK, PRK with crosslinking combined, or crosslinking alone, is to get the epithelium healed as quickly as possible. It’s not the steroid,” Dr. Loden said.

Crosslinking and intrastromal ring segments

Intrastromal ring segments, often referred to by the brand name Intacs (Addition Technology), are designed to improve corneal contour, making the cornea less irregular, flattening the cone, and making it more symmetric, Dr. Hersh said.
“That’s the general goal of using any corneal refractive surgery in keratoconus with or without crosslinking,” he added.
Dr. Hersh said he is a proponent of combining the two procedures and referenced a study he coauthored in 2019 that included 200 patients, looking at how crosslinking and Intacs work together and whether the procedures should be performed separately or concurrently.1 The study found that the combination of crosslinking and intrastromal ring segments leads to “substantial improvement in corneal topography” and sequential or concurrent procedures “show equivalent outcomes.” Dr. Rebenitsch said when he uses Intacs with crosslinking, he performs the procedure concurrently. He counsels patients that there is a chance they will have to be removed in the future but that there may be some residual effect if crosslinking is performed as well.
Dr. Hersh said he would recommend Intacs if the patient has poor best-corrected visual acuity, has an inability to wear contact lenses effectively, or if there is a major difference between the two eyes.
“If they are doing well with their glasses or contacts, don’t rock the boat,” he said, adding that Intacs can’t be used if the cornea is too thin in the paracentral area or if there is scarring where the segment would go.
Dr. Loden doesn’t use Intacs, citing that he has had to remove multiple Intacs.
“The cornea does not like foreign bodies in it; it tries to extrude them,” Dr. Loden said. “You can get thinning over the Intacs, you can get them eroding through the cornea. After a period of time, they want to extrude themselves from the eye.”
Dr. Hersh said he did a study of his Intacs population, following 600 patients for 10 years, and found the removal rate was 6–7%.2 One-third of these were for a medical issue (inflammation, infection, extrusion, etc.), and two-thirds were for optical or topography reasons, such as changing the segment size or position.
“In general, they seem to be quite safe,” Dr. Hersh said. “We’ve found the use of single-segmented Intacs may be more appropriate for keratoconus patients.”

Crosslinking and topography-guided PRK

All three ophthalmologists supported crosslinking combined with topography-guided PRK, provided the patient was a candidate (has a thick enough cornea).
“The only thing we’ve noticed with doing combination PRK and crosslinking is you’ll typically get more aggressive haze, and there are reports that you can get slower healing time and re-epithelialization of the cornea,” Dr. Loden said.
Dr. Hersh said his early results with combined crosslinking and topography-guided PRK show that the effect is similar to Intacs. He acknowledged, however, that Intacs vs. topography-guided PRK might be more appropriate for different kinds of patients.
Dr. Rebenitsch said he’ll usually perform topography-guided PRK concurrently with crosslinking or occasionally afterward if he did a PTK first.
“I wait a minimum of 6 months before doing any additional treatment,” he said. “There are differing views out there, but I personally would rather do a laser before crosslinking than after to avoid removing too much of the tissue that has now been crosslinked. That being said, there are reports of significant haze after crosslinking when laser was done concurrently, so there are many docs who recommend laser afterward only. With EBK and avoiding the removal of more than 50 µm of tissue with the laser, that has not been my experience though.”

An emerging refractive therapy

Dr. Hersh described another technique that he’s working on to benefit keratoconus patients refractively. It’s called corneal tissue addition for keratoconus, or CTAK. He said it uses preserved corneal tissue that is cut into customized shapes with a femtosecond laser.
“Depending on the location of the cone and thickness of the cornea, we are implanting preserved corneal tissue to preserve corneal topography and thicken the cornea,” he said.
About 10 patients have been treated with this technique so far and “it’s looking very promising,” Dr. Hersh said.
“The benefit of that is you can make different sizes and shapes, customized for the patient,” he said.

At a glance
• Crosslinking is meant to strengthen a weakened, bulging cornea, stopping progression of keratoconus. It doesn’t necessarily improve vision.
• Combining crosslinking with therapeutic refractive procedures can enhance a patient’s ability to wear soft contact lenses, improve visual acuity with glasses, or even improve uncorrected visual acuity.
• Therapeutic refractive options include intrastromal ring segments and topography-guided PRK.

About the doctors

Peter Hersh, MD
CLEI Center for Keratoconus
The Cornea & Laser Eye Institute
Hersh Vision Group
Teaneck, New Jersey

James Loden, MD
Loden Vision
Nashville, Tennessee

Luke Rebenitsch, MD
ClearSight Center
Oklahoma City, Oklahoma


1. Hersh PS, et al. Corneal crosslinking and intracorneal ring segments for keratoconus: A randomized study of concurrent versus sequential surgery. J Cataract Refract Surg. 2019;45:830–839.
2. Nguyen N, et al. Incidence and associations of intracorneal ring segment explantation. J Cataract Refract Surg. 2019;45:153–158.

Relevant disclosures

Hersh: Avedro (acquired by Glaukos), Lions Vision Gift,
Addition Technology
Loden: None
Rebenitsch: None


Hersch: phersh@vision-institute.com
Loden: lodenmd@lodenvision.com
Rebenitsch: dr.luke@clearsight.com

Crosslinking, combo procedures for refractive outcomes in keratoconus Crosslinking, combo procedures for refractive outcomes in keratoconus
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