Scleral approaches to presbyopia moving from niche to mainstream

Among the many options for presbyopia, scleral approaches stand out for their unique attempt to tackle the roots of the problem, restoring physiological function rather than aiming for optical compensation. They had a slow takeoff and limited acceptance, but step by step, through a long path of research and technological upgrades, they continue to move forward. According to several surgeons, they might be the ideal solution for plano or near-plano presbyopia, when the lens is still clear. They are minimally invasive procedures that preserve the visual axis, and patients’ visual experiences can be outstandingly good, even beyond what measurements say.

The predecessors of current scleral procedures as a treatment for presbyopia included anterior ciliary sclerotomies, scleral expansion bands and laser presbyopia reversal. These early attempts to restore accommodation were based on important intuitions but were abandoned due to complications and failure over time. However, they paved the way for the two approaches that are now being explored, one in FDA trials and one in international trials, with the scientific support provided by modern imaging and wavefront sensing methods.

More than near vision loss

“To truly understand presbyopia, we must go beyond the old idea of a simple loss of near vision or a loss of accommodation and embrace the concept that presbyopia is an aging eye. Jokingly, I tell my patients that they are experiencing the AGE syndrome, something we cannot escape,” Healio/OSN Board Member Mitchell A. Jackson, MD, said.

Source: Karolinne M. Rocha, MD, PhD

With age, cross-linkage occurs within and between molecules, leading to loss of elasticity and increased rigidity of all tissues and organs, including the eye. Jonas S. Friedenwald, MD, was the first to quantify ocular rigidity, establish the correlation between increased ocular rigidity and age, and hypothesize that decreased ocular elasticity may predispose to the development of age-related diseases such as age-related macular degeneration. Ioannis Pallikaris, MD, PhD, and co-authors further investigated this correlation and, in their paper on ocular rigidity published in Clinical and Experimental Ophthalmology, extended the idea to other age-related diseases such as glaucoma. “In this context, possible therapeutic approaches that aim to reduce ocular rigidity need to be evaluated,” they wrote.

Ocular rigidity also causes detrimental changes in accommodative biomechanics. In her VisioDynamics theory, AnnMarie Hipsley, DPT, PhD, redesigned the concept of accommodation as a dynamic system that involves not only the lens, but the entire eye apparatus.

“As age-related cross-linking occurs in the lens, the cornea, the sclera, the zonules and the ciliary muscles, the entire shell of the eye becomes like a serial cast that compresses the delicate internal physiological structures that reside beneath the outer scleral coat or the globe of the eye. These age-related changes progressively compromise the associated physiological and biomechanical functions of the eye organ,” she said.

Prior technology only addressed near vision, but according to Hipsley’s theory, that is not all that makes up presbyopia.

“Presbyopia affects all the age-related degrading functions of the eye, and the loss of visual accommodation is only one symptom of this aging problem. The change in anatomical positions, compromise in hydrodynamics as well as progressive anterior impingement of the angle structures are all further symptoms of the ‘aging eye.’ The presbyopic technologies of the future are those that will adopt this new way of looking at the problem and address the pathophysiological impact of presbyopia and the clinical manifestations that result from this aging eye disease. New findings and research are already illuminating that presbyopia is much more than a near vision correction market; rather, it is an age-related biomechanical and physiological dysfunction market,” she said.

Laser scleral microporation

The scleral laser anterior ciliary excision (LaserACE, Ace Vision Group) developed by Hipsley more than a decade ago has progressively evolved to become laser scleral microporation with the use of a new OCT-driven, touchless, automated 2.94 µm Er:YAG laser that creates tiny micropores in the sclera in a patented mathematical matrix.

Hipsley characterizes this as a tissue rejuvenation technique that improves the compliance of the sclera to accommodative forces from the ciliary muscles and extralenticular anatomy, restoring the biomechanics of the accommodation mechanism, which potentially affects accommodative amplitude, pseudoaccommodation, pupillary miosis, binocularity and other quality vision metrics that extend the effective range of focus of a presbyopic eye.

“Laser scleral microporation uncross-links the rigid scleral microfibrils and creates a region of rejuvenated sclera or new scleral tissue, according to our histology studies at Singapore National Eye Center,” she said.

The laser uses 225 µm spots to create a 5 mm × 5 mm array matrix of 49 micropores in four oblique quadrants of the sclera, a mathematical matrix that induces pliability and plastic properties.

“What we are basically doing is uncross-linking the aged scleral connective tissue, which decreases its biomechanical stiffness over key accommodative structures. This decreased ocular rigidity improves accommodative biomechanics and results in improved effective range of focus for all ranges of vision. Unlike other treatments, such as the pinhole lens, corneal inlay, multifocal lenses and multifocal laser ablation, that are static treatments, this approach is a dynamic, true therapy for restoring some accommodation, as well as improving natural depth of focus and pinhole effect that is lost with age,” Jackson said.

The procedure is performed binocularly, and the effect is enhanced by bilateral summation for distance and near. Patients can notice an improvement at day 1.

“We can now objectively measure the depth of focus and amplitude of accommodation by using ray tracing technology. The iTrace (Tracey Technologies) can objectively measure true accommodation, ie, the shift in refraction, by computing near and distance through-focus curves, and pseudoaccommodation related to changes in higher-order aberrations (HOA). Patients see better not thanks to true accommodation alone, but because this is combined with changes in HOA, especially spherical aberration,” OSN Technology Board Member Karolinne M. Rocha, MD, PhD, said.

Pseudoaccommodation, she said, depends on several factors. One is pupil size because the pupil can act as a pinhole when it contracts and shifts nasally for reading vision. The second factor, if patients are phakic, is the changes in higher-order aberrations in the lens during accommodation. Third is the residual spherical aberration from the cornea.

“Now we can measure all that, not only the change in refraction from distance to near, but the entire change in the optical system,” Rocha said.

“We published the long-term outcomes of patients who had the LaserACE procedure 10 years ago and who are now between 55 and 60 years of age. They still have a great distance vision and can read J3 or better at near. In the new studies, we measure patients before and after the procedure, and we see some changes, an extended range of vision due to a combination of sphere shift through true accommodation plus the pseudoaccommodation,” she said.

VisAbility micro insert

The VisAbility micro insert for presbyopia (Refocus Group) is an updated version of previous scleral bands, aimed at expanding the area between the sclera and the ciliary muscles.

“By inserting a microstent in the sclera, posterior to the limbus in all four quadrants, you expand the scleral diameter and put the zonules on stretch to reestablish accommodation. The theory is that the lens grows as you get older and the zonules lose tension. It is like a marionette puppet, which cannot move if the strings are not on stretch,” Healio/OSN Board Member Kenneth A. Beckman, MD, FACS, said.

The inserts are placed midway between the rectus muscles, in each quadrant, 4 mm posterior to the limbus, through a 4 mm long tunnel at a depth of 400 µm.

“Midway because you try to avoid the ciliary circulation within the muscles, which carries the blood flow to the anterior segment,” he said.

The creation of scleral tunnels is now automated, ensuring correct length, depth and location. The inserts are micro-thin, the size of a grain of rice, and are held in place by a two-piece locking micro insert. The procedure is meant to be binocular, although in the studies it was performed one eye at a time with the second eye generally completed no sooner than 14 days after the first surgery.

Compared with other technologies to correct presbyopia, the procedure holds many advantages, Beckman said.

“It is a binocular procedure, as opposed to corneal inlays, and it does not affect the visual axis, so some of the risks related to corneal scarring are not there. It is external to the eye, it does not rely on multifocality, and it aims at restoring accommodation, so as to give a natural near reaction. It is reversible; you can remove the stents at any time,” he said.

The learning curve is not difficult, and the procedure takes approximately 20 minutes per eye, with the patient sedated but awake.

“Once you do a handful of them, you get used to the insertion because it is automated. Patients don’t have significant pain. They have redness because the procedure is performed after lifting the conjunctiva over 360°,” Beckman said.

A large target population

Both scleral procedures are targeted to a specific subset of presbyopic patients, emmetropes with less than 1 D of astigmatism, with early presbyopia and no cataract, who are already using spectacles all the time for reading.

“Not earlier, when there is still accommodation. Patients who are 42 and can still read without spectacles are not good candidates for scleral microporation, but if they already cannot read without spectacles, that’s the right time to do it,” Jackson said.

“You want to find somebody who is emmetropic at distance, usually between +0.5 D and –0.5 D. Our typical VisAbility patients have been between 45 and 60 years old, early to mid-level presbyopics who need between 1 D and 2 D of presbyopic improvement,” Beckman said.

An interesting and potentially large subset of patients might be those who have previously undergone refractive surgery and by the age of 40 to 50 are still happy with their distance but not with their near vision.

“Since they are close to emmetropia at distance, they can undergo a scleral procedure as a supplement for near. It is hard to find patients who are naturally emmetropic, but we are creating emmetropes every day by doing refractive surgery. These are the patients who become presbyopic and are no longer so happy. We may find this will be the biggest market, tens of millions who do not have an appropriate treatment now,” Beckman said.

Regarding patients who underwent LaserACE years after having PRK, Rocha said, “They had the LaserACE procedure years ago and still now they can read, use the computer, the cell phone and iPad without spectacles. It is like an extended range of vision from distance to intermediate and near,” she said.

Better than numbers suggest

Both laser scleral microporation and VisAbility procedures also share the benefit of providing better vision than numbers suggest, deriving from an overall improvement in biomechanics.

“In my experience with VisAbility, I can say that the numbers are already quite good, but what you see when you have an accommodating system, lens or scleral, is that patient satisfaction is greater than the numbers would suggest,” Kevin L. Waltz, OD, MD, said.

One of his patients in the FDA trial was presbyopic in his late 50s and had been wearing glasses for more than a decade for reading. While sitting in the waiting room before one of his follow-up visits after VisAbility surgery, he was playing computer games on his smartphone without glasses.

“That’s pretty small, on your phone, and it is very small when you do games; everything is moving fast, and you don’t have a lot of time to read. I was watching him in fascination. He told me he never used to play games when wearing glasses and took up this new pastime after undergoing the procedure. It was a very interesting observation. I found that a lot of our patients took up that hobby of playing games on cell phones in the VisAbility trial. This told us that something very positive was happening, that the functional acuity was even better than the numbers told us,” he said.

“We are seeing an improvement in distance vision as well, not just near vision, and an improvement in stereopsis,” Jackson said.

“The ciliary muscle that is attached to the scleral wall can contract more,” Rocha said. “That will enhance the patient’s natural residual accommodation. Pseudoaccommodation is also enhanced. If patients have smaller pupils, as many older patients have, this can add to the true accommodation. The optical system works together, and we were able to measure dynamic changes of the pupil when patients tried to read, plus a shift in HOA from the lens.”

Good clinical trial results

Two-year data from the international trial show that laser scleral microporation meets the FDA requirement of having 75% of patients with stable 20/40 or better at near.

“With our first-generation laser, handheld, we had 89% of patients achieving 20/32 or better, 50% are seeing 20/20, even better than FDA requirements, and maintaining these results at 2 years. With the new laser, results are even better. My patients can now read J1+ the same day of surgery, quite amazing,” Jackson said.

No major complications occurred. Because the visual axis is not involved, there are no threats to vision.

“If you go too deep, you can potentially get a perforation, but it is a microperforation with the new laser, and since it is now OCT guided, it is not going to happen. With the previous 600 µm spot laser, perforation occurred a few times but caused no sight-threatening issues,” Jackson said.

Two-year VisAbility data have been submitted to the FDA, and the procedure is now in the third year of study.

“Results are stable over time. Patients are very happy. It is quite impressive. We did not have any major complications. One patient in the study had the implant removed, which is easy and safe to do. The main concern is cutting off circulation with the anterior segment. This can be identified by monitoring the pupil reaction. During surgery, the pupil tends to dilate. During the immediate postop period, the patient is monitored to see when the pupil reaction returns. Once the pupil reaction returns, you know the circulation is not compromised,” Beckman said.

Cosmetic issues should not be a concern, according to Waltz. In the typical patient, under normal circumstances, the micro inserts are covered by the eyelids.

“The procedure is safe, comfortable to patients and not cosmetically an issue,” Waltz said.

A bright potential future

If approved by the FDA, scleral procedures may eventually climb out of the niche where they have been confined for many years and become mainstream for the correction of early presbyopia.

“We have a surprisingly long track record, but not as long as corneal or lens procedures. Yet, the VisAbility has come along because a lot of us were uncomfortable with the limitations in treating presbyopia with cornea or lens procedures. It gives a new way to treat presbyopia, but it is a new kind of surgery, and many of us are not familiar with the sclera as much as with cornea or lens. It is a new skill to learn,” Waltz said.

Jackson believes that between the two, scleral microporation will become more popular because it is easier to perform, faster and more cosmetically acceptable immediately postoperatively.

“It is an all-laser 5- to 10-minute procedure like any refractive procedure, automated, OCT guided. VisAbility may take up to 50 minutes, but this is still too long for modern refractive surgery,” he said.

“What I see is that scleral microporation is to VisAbility as LASIK is to PRK. Both procedures are good, as both PRK and LASIK were, but LASIK is the one that really took off. Laser microporation is the LASIK of the scleral space. Surgeons are going to like it because it is automated, like LASIK, and therefore less reliant on surgeon’s experience and capability, which is better for mainstream acceptance,” he said.

Both procedures also have the potential to enhance other procedures.

“In the future, if we implant an accommodating lens and don’t get as much accommodation as we like, we could conceivably add VisAbility to enhance that,” Waltz said.

Besides also enhancing the effect of accommodating lenses, scleral laser microporation may help presbyopia drops work better and at a lower dosage, Jackson said.

“And the most interesting future challenge is seeing whether the rejuvenation effect on the sclera and improvement on the overall eye function might help prevent age-related diseases, such as AMD and glaucoma,” he said. – by Michela Cimberle

• References:
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• For more information:
• Kenneth A. Beckman, MD, FACS, can be reached at Comprehensive Eye Care of Central Ohio, 450 Alkyre Run Drive, No. 100, Westerville, OH 43209; email: kenbeckman22@aol.com.
• Mitchell A. Jackson, MD, can be reached at Jacksoneye, 300 N. Milwaukee Ave., Suite L, Lake Villa, IL 60046; email: mjlaserdoc@msn.com.
• AnnMarie Hipsley, DPT, PhD, can be reached at Ace Vision Group, 39655 Eureka Drive, Newark, CA 94560; email: ahipsley@acevisiongroup.com.
• Karolinne M. Rocha, MD, PhD, can be reached at Storm Eye Institute, Medical University of South Carolina, 167 Ashley Ave., Charleston, SC 29425; email: karolinnemaia@gmail.com.
• Kevin L. Waltz, OD, MD, can be reached at 5051 Buttonwood Crescent, Indianapolis, IN 46228; email: kwaltz56@gmail.com.

Disclosures: Beckman reports he is a consultant for Refocus Group. Jackson reports he is global medical director of Ace Vision Group. Hipsley reports she is founder of Ace Vision Group. Rocha reports she is a consultant and advisory board member of Ace Vision Group. Waltz reports no relevant financial disclosures.

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