September 2017

CATARACT

Lens regeneration: The future is now


by Liz Hillman EyeWorld Staff Writer

Promising results in congenital cataracts with research moving toward regeneration in adults

It was named one of the eight Notable Advances by Nature Medicine in 2016 and called “one of the finest achievements in the field of regenerative medicine,” according to Yizhi Liu, MD, PhD, professor, director of Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Dr. Liu was the designer of the novel surgery used in this lens regeneration research, for which he received the Gold Medal at the 30th annual meeting of the Asia-Pacific Association of Cataract and Refractive Surgeons.1
During a symposium that looked at new innovations, Haotian Lin, MD, PhD, one member of Dr. Liu’s research group, presenting the research on his behalf, described a new surgical technique for congenital cataracts that regenerated the patient’s lens within 6 months.
The research, published in March 2016 in Nature, involved 12 children (24 eyes) under 2 years old with bilateral congenital cataract.2 A 1–1.5 mm peripheral capsulorhexis was made, the cataract was removed using irrigation/aspiration, and the patient received atropine and an antibiotic/steroid. Then, they waited. The lens capsule opening had healed by 1 month, and at 6 months postop, a regenerated lens had formed.
“The congenital cataract is a very challenging problem,” Kang Zhang, MD, PhD, professor of ophthalmology, chief of ophthalmic genetics, founding director of the Institute for Genomic Medicine, and co-director of biomaterials and tissue engineering, Institute for Engineering in Medicine, University of San Diego, told EyeWorld.
Because the infant eye is still growing and changing, making it difficult to estimate the power of an intraocular lens, completing a traditional cataract surgery with an IOL is controversial under the age of 2. However, surgeons want to make an optically clear path so images can be adequately superimposed on the retina to avoid amblyopia, Dr. Zhang said.
“The patient has to undergo some kind of procedure, however, this procedure, as you can imagine, carries risks. … You have to, in many cases, remove the entire lens out of the eye. The lens that’s developing adheres to the vitreous tightly, so removing the lens with a big incision and disrupting the vitreous leaves the potential for a lot of complications, macular edema, corneal edema, increased intraocular pressure, infection, to name a few,” Dr. Zhang said.
“Rather than removing the entire lens, we thought, what if we can figure out a way to regenerate the patient’s lens using their own stem cells?” he said.
Previous research has shown the ability of other animals to regenerate lenses under certain conditions.3 Dr. Zhang said the complication of posterior capsule opacification after cataract surgery is also a clue of the presence of stem cells. Prior to this human trial, Dr. Liu’s research found lens epithelial stem/progenitor cells (LECs) at the edge of the original capsulorhexis in pediatric patients.
Whether the equatorial LECs were stem cells, however, required further research. Dr. Liu’s team showed human LECs are capable of cell renewal and how the number of LECs decrease with aging but increase after injury or stimulation.
Proliferative LECs at the equator were found to be stem cells, according to Dr. Liu. Dr. Zhang more specifically said it’s now known that lens stem cells are under the entire anterior capsule. A traditional 6–7 mm capsulorhexis destroys 80% of these stem cells, he explained.
“What we found is in mice, since we knew stem cells were in the anterior capsule, we have to find a way to minimize its damage. We thought, in the case of children with cataracts, cortical cataracts are very soft, they’re easily removed with gentle I/A, so we can create a small incision that’s easily sealed and with minimal trauma to the lens stem cells to let it regenerate,” Dr. Zhang said.
Making a manual 1–1.5 mm capsulorhexis to minimize stem cell damage, however, is not easy, Dr. Zhang said, though he noted it could be performed with a femtosecond laser.
“But when we did the surgery it was not an option, so we have very skilled surgeons, in this case Dr. Liu … do the surgery. He’s a very experienced surgeon,” Dr. Zhang said.
After testing this technique in animal models, a clinical trial of 12 patients (24 eyes) with congenital cataracts compared to a control group of 25 patients (50 eyes) who received traditional cataract surgery showed comparable safety data between the two groups. However, the novel group had significantly better clinical results, according to the research. Patients in the test group regenerated a lens within 6 months and, according to Dr. Liu’s group, it showed a certain degree of thickness, functional refractive power, and accommodative ability.
A small number of patients redeveloped cataract in the regenerated lens. “We did not correct the underlying mutation or cause for cataract,” Dr. Zhang pointed out. But in those cases, the lens remained clear for about a year, giving the
patients critical time with clear vision to avoid amblyopia and to continue growth of the eye to the point where traditional cataract surgery with an intraocular lens would be safer. Dr. Zhang also said there’s the possibility of performing the modified cataract surgery again to encourage another lens to grow.
“If I were able to have my own lens, I would rather have my own lens, so I think our procedure gives us an alternative to extracting the lens material,” Dr. Zhang said.
What’s more, he said the research team is working on an idea to speed up the regenerative process using a 3-D printed biodegradable lens scaffold that contains growth factors to promote regeneration. This scaffold, he said, would be injected into a small hole in a manner similar to an ophthalmic viscoelastic device. As the patient’s own lens fibers and proteins grow, the scaffold would biodegrade.
“Cataract surgery is so successful—you will have your vision back within the next day or two,” Dr. Zhang said, adding that visual recovery 6 months later with the regenerative technique would be less well received. “However, if this can be done within a timeframe of 2 months, I think most ophthalmologists and patients would be able to accept that.”
In addition to providing another option for congenital cataract surgery, Dr. Zhang said the long-term goal is to use this regenerative technique for adult, age-related cataracts as well. “We could actually restore our accommodation this way,” he said.

References

1. Stower H, et al. Notable advances 2016. Nat Med. 2016;22:1374–1376.
2. Lin H, et al. Lens regeneration using endogenous stem cells with gain of visual function. Nature. 2016;531:323–8.
3. Del Rio-Tsonis K, et al. Eye regeneration at the molecular age. Dev Dyn. 2003;226:211–24.

Editors’ note: Drs. Liu and Zhang have no financial interests related to their comments.

Contact information

Lin: yzliu62@yahoo.com
Zhang: k5zhang@AD.UCSD.EDU

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