Less than two months after FDA approval of Alcon’s AcrySof IQ PanOptix Trifocal IOL and AcrySof IQ PanOptix Toric Trifocal IOL on August 27, early users report high adoption rates for the lenses, which demonstrate the ability to correct near, intermediate, and distance vision. A robust adoption rate is consistent with the experience of surgeons who have been implanting the PanOptix in more than 70 countries since 2015.
“I’m already implanting seven or eight PanOptix IOLs per week,” says Elizabeth Yeu, MD, of Virginia Eye Consultants, one of the trial investigators. “The strong possibility that patients will not have to wear glasses anymore is a very attractive option to them.”
Surgeons say that it may be simpler to explain the lens to patients, compared to other options in the past.
“With today’s other premium lens options, we’re used to asking patients if they want a monovision solution for distance and near clarity,” says Kerry Solomon, MD, a PanOptix investigator from Mount Pleasant, South Carolina. “If they’re not interested in monovision correction, we ask them if they’d like to have their vision for intermediate tasks, such as working on the computer and using cell phones and back-lit items, and use readers for printed material. Would they prefer to make accommodations by using computer glasses? It gets to be a lengthy discussion that, at times, can lead to some confusion. Now we can just ask, “Would you like to be less dependent on glasses for distance, intermediate and near activities? It’s an easy conversation to have, and so far, my adoption rate has been terrific.”
In an FDA clinical study of 243 patients implanted with either the PanOptix lens or a control lens at 12 U.S. investigational sites, a total of 129 patients (256 eyes) were implanted with the PanOptix (127 in both eyes and two patients in one eye). A total of 114 patients (225 eyes) were implanted with the control lens (111 in both eyes, three in one eye).
Six months after implantation, according to the study, the average best corrected distance vision in one eye was approximately 20/20 for each study group. For intermediate distance, the vision in one eye with the PanOptix lens was approximately 20/25 compared to 20/40 for the control group. The vision for near distance correction with the PanOptix lens was approximately 20/25, compared to 20/63 for the control group. Overall, there were no safety concerns during the study, the company says.
The PanOptix trifocal IOLs are made of same material that was used to create the AcrySof ReSTOR IQ IOL, which has been implanted in more than 120 million eyes globally. The toric PanOptix models were designed by placing new trifocal features on parent ReSTOR Toric IQ IOLs. Alcon officials say the PanOptix intraocuar lens has unique properties made possible by the company’s new Enlighten Optical Technology, which establishes three focal points: one at near (16 inches); a second at intermediate (24 inches); and a third that redirects light energy for improved distance vision.
The technology allows 88 percent total light utilization at a 3-mm pupil size, reducing dependence on pupil size in varied lighting conditions. A 4.5-mm diffractive zone divides incoming light to create the effective intermediate and near add powers. The anterior surface is designed with negative spherical aberration to compensate for the positive spherical aberration of the cornea. The posterior surface of the optic of the AcrySof IQ PanOptix Trifocal Toric IOL is marked with six indentations (three on either side) on the flatter meridian of the optic. Below are the corrective parameters of both lens types:
• Spherical powers: 6 to 30 D in
0.5-D increments; 31 to 34 D in 1-D increments.
• Add powers: 2.17-D intermediate and a +3.25-D add power at the intraocular lens plane, representing approximately +1.65 D and +2.35 D at the corneal plane after implantation, respectively, for the average eye.
• Cylinder powers (for four toric designs): 1.5, 2.25, 3 and 3.75 D.
In one patient-reported outcome measure, 80.5 percent of study
participants (99 of 123) who had the PanOptix implanted said they “never” had to wear glasses during the previous seven days.
Alcon notes that the PanOptix can potentially create visual disturbances at night that can be worse than those created by monofocal IOLs. Potential disturbances include glare, rings around lights, starbursts and reduced contrast sensitivity (especially in dim lighting). In the study, for example, 45.2 percent of PanOptix patients were bothered by glare vs. 30.6 percent of the monofocal patients, and 48.8 percent of PanOptix patients were bothered by halos vs. 16.4 percent of the monofocal patients. These side effects may make it more difficult to see while driving at night or completing tasks in low lighting conditions, according to the company.
Alcon plans to begin training U.S. ophthalmologists and making inventory of PanOptix and PanOptix Toric IOLs available through the rest of 2019 into early 2020.
One topic of great interest will be which patients are good candidates for these IOLs. “You need to use the PanOptix on patients with healthy corneas,” says Dr. Solomon. “You want to make sure the astigmatism is regular, not irregular. No basement membrane dystrophy or any significant dry eye. You want to treat that first. A healthy ocular anatomy and healthy retina is required. We should be looking at patients with generally healthy eyes who are interested in being less dependent on glasses.”
One group of patients was purposely excluded from the FDA trial—those who had undergone refractive surgery. “Speaking to some of my European colleagues, it’s not quite clear yet how this lens performs in that setting,” says Dr. Solomon. “But I think we’ll learn more in the very near future as more discussion about this lens and that topic ensues.”
A Major Advance in Transplants
On July 25, Kohji Nishida, MD, and his team at Osaka University performed the first human corneal transplant using sheets of corneal epithelial tissue made from induced pluripotent stem cells. The new treatment gained approval from Japan’s health ministry in March, and a woman in her 40s suffering from limbal stem cell deficiency was the first to receive the treatment. At a one-month follow-up, her cornea remained clear.
Corneal diseases are the most common cause of vision loss globally,1 and corneal transplants are among the transplant procedures in highest demand.1 There’s a significant shortage of donor corneas, however, with only one cornea available for every 70 needed.2
Lab-engineered corneas may help narrow this gap. Induced pluripotent stem cells have a high differentiation potential and can proliferate indefinitely, making them a potentially unlimited source of transplantable cells.3
Last year, Dr. Nishida participated in a study on differentiating human induced pluripotent stem cells into distinct ocular lineages. The researchers used five different isoforms of laminin, a basement membrane protein, as a substrate for the cell cultures and found that distinct laminin isoforms determined selective differentiation of human iPSCs into eye-like tissues, including neural crest and retinal cells.
Figure 1. An induced pluripotent stem cell-derived corneal epithelial cell sheet.4
The researchers report that culturing hiPSCs on LN332E8 eliminates the need to pipette away non-epithelial-like cells for corneal epithelial cell sheet production, which was necessary for a previously-attempted method.4 The researchers also observed that their new laminin differentiation method shortens the culture period.5 Ryuhei Hayashi, PhD, one of the study’s authors, explains that the binding affinity of laminin and integrins determines the characteristics of hiPSC colonies. “On LN332E8, which has a moderate binding affinity, YAP protein, a sensor for mechanical stress, remained in the nuclei throughout the colony. The presence of YAP promotes corneal epithelial differentiation from human induced pluripotent stem cells. The resulting cell sheets expressed major corneal epithelial markers such as PAX6 and keratin12.”
Embryonic stem cells and mesenchymal stem cells are alternatives, but these have faced clinical hurdles from the ethical debate surrounding embryonic stem cells and the challenges of immunosuppression for donor tissue. Donor iPSCs were used by Dr. Nishida’s team for the patient suffering from limbal stem cell deficiency, but iPSCs also have the potential for autologous transplantation, since these stem cells can be obtained from the patient herself with no immune rejection risk.3
Four more transplant procedures have been approved by the health ministry, and iPSC therapy may be ready for clinical use in five years. REVIEW
1. Robaei D and Watson S. Corneal blindness: A global problem. Clin Exp Ophthalmol 2014;42:3:213-4.
2. Gain P, Jullienne R, He Z, et al. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol 2016;134:2:167-173.
3. Zhu J, Slevin M, Guo B, Zhu S. Induced pluripotent stem cells as a potential therapeutic source for corneal epithelial stem cells. Int J Ophthalmol 2018;11:12:2004-2010.
4. Hayashi R, et al. Coordinated ocular development from human iPS cells and recovery of corneal function. Nature 2016;531:376-380.
5. Shibata S, Hayashi R, Nishida K, et al. Selective laminin-directed differentiation of human induced pluripotent stem cells into distinct ocular lineages. Cell Rep 2018;25:1668-1679.