Source: Healio Interviews
Disclosures: Agarwal reports no relevant financial disclosures. Holladay reports he is a consultant for AcuFocus and Ocuphire Pharma. Majmudar reports no relevant financial disclosures. Rocha reports she is a consultant for Allergan.
November 03, 2020
9 min read
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Small-aperture optics can improve depth of focus without compromising vision

Source: Healio Interviews
Disclosures: Agarwal reports no relevant financial disclosures. Holladay reports he is a consultant for AcuFocus and Ocuphire Pharma. Majmudar reports no relevant financial disclosures. Rocha reports she is a consultant for Allergan.
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A pinhole effect, achieved through surgery, pharmacologic agents, IOLs or inlays, can treat significant irregular corneal astigmatism and higher-order aberrations, whose effects are minimized by reducing pupillary aperture.

A smaller pupil can reduce incident straylight, help improve visual acuity, and reduce glare and halos.

Jack T. Holladay, MD, MSEE, FACS
Each of the small-aperture optic categories will evolve along their own path because they each best serve different groups of patients, according to Jack T. Holladay, MD, MSEE, FACS.

Source: Jack T. Holladay, MD, MSEE, FACS

The pinhole effect/small-aperture optics is an effective therapy to increase depth of focus, OSN Technology Board Member Karolinne M. Rocha, MD, PhD, said.

“You really want to achieve that ideal pupil size that enhances depth of focus without compromising distance vision and contrast,” she said.

Small-aperture optics is often the only modality that benefits patients with higher-order aberrations and refractive error after refractive surgery. It provides “so many people who have no other alternatives a way of getting better vision,” OSN Optics Section Editor Jack T. Holladay, MD, MSEE, FACS, said.

“None of the other modalities, such as topographic-guided or wavefront-guided LASIK, have been able to provide the quality we can with a pinhole. They’ve improved, but they still have difficulty achieving the same results you’d get with a pinhole or a rigid contact,” Holladay said.

Pinhole pupilloplasty

Ashvin Agarwal, MD, is a proponent of surgical means to achieve the effect. Agarwal and colleagues published a pinhole pupilloplasty technique in Journal of Cataract and Refractive Surgery, advocating it in all cases of higher-order aberrations arising from corneal surface irregularity.

The technique’s concept is to achieve a pinhole aperture that allows light through and cuts off all peripheral aberrant rays.

Ashvin Agarwal, MD
Ashvin Agarwal

“The target is to achieve a pinhole pupil of approximately 1.5 mm in diameter through pupilloplasty. I’ve adopted a single-pass four-throw technique while performing pinhole pupilloplasty,” Agarwal said.

Patients with higher-order aberrations with a clear central cornea and normal iris tissue are typically good candidates for the procedure. Additionally, patients who underwent penetrating keratoplasty or radial keratotomy, or those with keratoconus who have irregular astigmatism, can also benefit from the procedure.

The surgeon performs a single-pass four-throw technique, modified slightly for the pinhole pupilloplasty. More iris tissue is incorporated from the pupillary margin into a 10-0 needle, which is passed through the iris tissue more centrally so that the iris tissue close to the center of the pupil can be approximated.

“Intraoperatively, I target the pupil to be centered on the Purkinje 1 image arising from the anterior corneal surface. This is a coaxial light reflex arising from the light of my Lumera microscope. Often, three to four attempts are needed to achieve the pinhole pupil that is well centered around the Purkinje 1 reflex,” he said.

A rewarding technique

The technique offers extended depth of focus from +1.5 D to –2.5 D and can improve visual acuity due to the added pinhole effect. Patients typically experience significant improvement in distance, intermediate and near vision under photopic and mesopic light conditions, Agarwal said.

“I would suggest the readers should try doing pinhole pupilloplasty after learning single-pass four-throw pupilloplasty in appropriate cases. The surgical outcomes and patient satisfaction are truly rewarding,” he said.

This method spares the lens and cornea and allows a surgeon to put a lasso on the iris and bring it down to the ideal pupil size. It can provide “tremendous” results for patients with higher-order aberrations and greatly improve visual acuity, Holladay said.

The ideal candidate for pinhole pupilloplasty would be a patient with a moderate, intermediate or severe cataract who may need a pinhole smaller than the typical 1.36 mm aperture provided by the IC-8 IOL (AcuFocus), Holladay said.

Pinhole pupilloplasty can be a great option for patients with highly aberrated corneas, but surgeons should take care in finding the ideal pupil size for each patient. Holladay and colleagues created a titanium-based circular device, with various pinhole sizes ranging from 0.5 mm to 4 mm, that can be held up to a patient’s eye before surgery to customize the best pinhole size.

Patient selection is key

There is a balance among diffraction, higher-order aberrations and refractive error that must be taken into consideration when pupil size is determined, Holladay said.

“This device lets us find the optimal pinhole size for each patient with those two things at either end of the spectrum, which you can’t figure out quantitively from a calculation. This determines the optimal pinhole size for us empirically. You can go to surgery and know you’ve given the patient the best pinhole size for their higher-order aberrations and refractive error. You’ve customized that pinhole to be best for the patient,” he said.

Patients with retinal issues may not be good candidates for a permanent pinhole pupilloplasty, in that the procedure can make it difficult to look into the back of the eye and may compromise a dilated fundus exam, Rocha said.

Karolinne M. Rocha, MD, PhD
Karolinne M. Rocha

Also, surgeons can have difficulty looking at the periphery of the eye in those who underwent surgical pinhole pupilloplasty and may have difficulty dilating patients with diabetic retinopathy who may need panretinal photocoagulation, she said.

“Make sure the patient has a healthy eye. We need long-term follow-up for these patients to make sure they don’t develop chronic cystoid macular edema or complications related to the iris suture,” she said.

Pharmacologic options

No pharmacologic agents that induce a pinhole effect are yet approved by the FDA, but several are in clinical trials.

In some patients, such agents that would extend depth of focus through enhanced pseudoaccommodation with the pinhole effect and miosis would be more appropriate than surgery, Rocha said. These drug therapies can help treat early presbyopes who may not yet be candidates for laser vision correction or who are not ready for lens surgery.

“Having a reversible drop to help these candidates would be fantastic, especially during a transition in vision,” she said.

Presbyopia Therapies, Ocuphire Pharma, Orasis Pharmaceuticals and Allergan all have miotic therapies in development. The agents constrict the pupil to not allow for full dilation typically reached in normal or dim light.

According to ClinicalTrials.gov, Allergan’s AGN-241622 is in phase 1/2 study in healthy participants with presbyopia, and a phase 3 efficacy study of AGN-190584 in participants with presbyopia is completed.

Presbyopia Therapies’ PRX-100 ophthalmic solution met primary efficacy and safety endpoints in a phase 2b study. The therapy demonstrated a three-line or greater improvement in monocular distance corrected near acuity in patients between the ages of 48 and 64 years, according to the company.

Additionally, Orasis’ CSF-1 agent reached its primary endpoint in a phase 2b clinical trial and demonstrated statistically significant improvement in distance corrected near visual acuity with a three line or more gain, according to the company.

Holladay said that Nyxol (Ocuphire Pharma), a preservative-free ophthalmic solution containing 1% phentolamine mesylate, can effectively decrease the size of the pupil. It is currently in three phase 1 and four phase 2 trials with more than 230 patients and is being developed under the 505 (b)(2) pathway, according to the company.

Visus Therapeutics is developing Brimochol, a proprietary formulation of carbachol and brimonidine tartrate. It results in a strong miotic effect that can be longer acting. In studies, Brimochol has shown an ability to achieve target pupil size and functional near visual acuity at 8 hours past its dose, Richard L. Lindstrom, MD, reported at the virtual European Society of Cataract and Refractive Surgeons meeting.

A reversible option

These miotic agents may provide the “sweet spot” for patients in terms of therapies designed to treat presbyopia, Parag A. Majmudar, MD, president and chief medical officer of Chicago Cornea Consultants, said.

“These drops will take advantage of the small-aperture optics. Most of these drops have an 8- to 12-hour duration of action, so it should not be much of an issue at nighttime if used in both eyes. The drops will be best used in a population of patients that won’t have dependence on night vision or who have work or hobbies that depend on night vision,” he said.

Parag A. Majmudar, MD
Parag A. Majmudar

The duration of action is an advantage for the drop technology. If a patient experiences poor outcomes or complications, the drops can be discontinued, and the effect wears off quickly, Majmudar said.

Younger patients with higher-order aberrations and refractive errors, usually after refractive surgery, who are not ready for cataract surgery may benefit more from a pharmacological approach, Holladay said.

Inlay and IOL options

Devices offer a more permanent solution in terms of small-aperture optics, but patient selection is key and complications can be greater. The Kamra corneal inlay (CorneaGen), approved by the FDA in 2015, is an alternative treatment for presbyopia and is indicated for phakic presbyopes between the ages of 45 and 60 years. It is indicated for patients who do not require glasses or contact lenses for distance vision but who need near vision correction of +1 D to +2.5 D, Majmudar said.

The inlay is 3.8 mm in diameter, with a 1.6 mm diameter opening in the center of the device. It is made of polyvinylidene fluoride and carbon and is positioned over the central zone of the cornea in a patient’s nondominant eye.

Majmudar said his clinic was one of the first to use the technology after its FDA approval, and the device was implanted in about 25 to 30 patients. Most of the patients have experienced positive outcomes, but the difficulty of implanting the inlay may limit its widespread adoption.

“We also did have to adjust our endpoints. Initially we thought it could treat any range, from a little bit of hyperopia to myopia, but it really couldn’t. It needed a certain sweet spot for that, at least for the corneal application,” he said.

The inlay is primarily best for younger patients, Holladay said. The technology has been used for nearly 14 years, and the long-term outcomes and complications appear to be good. However, a surgeon must be an accomplished refractive corneal surgeon to implant the inlay. Most cataract surgeons are not corneal surgeons, so patients must be referred to a corneal specialist if an inlay is needed, he said.

Patients who have an early, moderate or severe cataract with refractive errors after refractive surgery are good candidates for the IC-8 IOL. The IOL has a pinhole in its center to increase a patient’s range of vision by extending the focus of light rays that enters the eye, Holladay said.

Positive results in Europe

According to a 2020 Clinical Ophthalmology study, the IC-8 IOL eliminates unfocused peripheral light rays with its small aperture, allowing the central rays to pass through. This reduces blur circle size and improves image resolution for intermediate and near vision, with little change in distance vision.

A 2019 study in Eye investigated visual outcomes after cataract surgery in 126 patients who were implanted monocularly with the IC-8 IOL. More than 90% of patients without preexisting ocular pathology achieved uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA) and uncorrected near visual acuity (UNVA) of 6/12 (20/40) or better in the IC-8 eye. Binocularly, 98% of patients achieved UDVA of 6/9 (20/30), 94% achieved UIVA of 6/12 and 91% achieved UNVA of 6/12 or better.

The IOL is not yet approved by the FDA for use in the United States. If approved, it could be used effectively in the millions of patients who have refractive errors after refractive surgery, Holladay said.

“Patients with cataracts or even those who are presbyopic in their 50s or 60s with an early cataract who wish to improve their intermediate and near vision and get rid of their higher-order aberrations will be good candidates for the AcuFocus IC-8,” he said.

Each of these small-aperture optic categories will evolve along their own path because they each best serve different groups of patients, Holladay said.

Everything is about patient selection when it comes to this technology. All of the modalities work, but finding the best technology for the appropriate patient is key in using small-aperture optics, Majmudar said.

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