Exploring lens regeneration after cataract surgery

Take-home message: Functional lens regeneration was achieved in infants undergoing surgery for congenital cataract using a novel minimally invasive technique that maintains lens capsule integrity and preserves lens epithelial stem cells.

Reviewed by Kang Zhang, MD, PhD

Functional lens regeneration may be moving a step closer to reality from hypothesis.

In the March 17, 2016, issue of Nature, Kang Zhang, MD, PhD, and colleagues reported results of a clinical trial in which functional lens regeneration was achieved after congenital cataract surgery performed with a novel minimally invasive technique [Lin H, et al. Nature. 2016;531:323-328].

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Designed to maintain lens capsule integrity and preserve the lens epithelial stem cells (LECs), their surgical strategy involves removal of the lens contents and/or cortical opacities through a small, 1.0 to 1.5 mm, peripheral capsulorhexis using a 0.9 mm phacoemulsification probe.

After demonstrating in rabbit and macaque models that the surgical technique resulted in functional lens regeneration, the research advanced into a pilot clinical trial co-led by Yizhi Liu, MD, PhD, professor and director, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

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The randomized study enrolled infants aged 0 to 1 years with bilateral congenital cataract and assigned 12 children to be operated on with the new method and 25 children to undergo conventional cataract surgery. The procedure in the control group involved a 6-mm anterior continuous curvilinear capsulorhexis plus a posterior continuous curvilinear capsulorhexis; an IOL was either implanted primarily or the eyes were left aphakic and children were fitted with glasses or contact lenses for refractive correction.

After the minimally invasive procedure, the small capsule opening healed within 1 month and a transparent lens structure formed within 3 months. During follow-up to 8 months, the lens attained central thickness comparable to a normal lens while refractive power and accommodative amplitude increased.

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Achieved visual acuity was comparable in the two surgical groups.

However, visual axis opacification occurred in only a single eye that underwent the new procedure (4.2%) versus 42 control eyes (84%). Significantly lower rates of other complications also occurred after the new procedure compared with the standard operation, including corneal edema (8.3% versus 30%), anterior chamber inflammation (16.7% versus 74%), ocular hypertension (0% versus 18%), and a need for additional laser surgery (0% versus 84%).

LECs as stem cells

In addition, the life-long glaucoma risk, which is associated with the current congenital cataract surgery, is expected to be significantly lower due to minimal disruption of the ocular structure, although the investigators noted this needs to be verified.

Dr. Zhang noted that the landmark accomplishment is notable both because of its implications for overcoming current challenges in managing congenital cataract and because it may signal hope for an exciting new era in regenerative medicine.

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“Obviously, further study in larger patient cohorts with longer follow-up is needed to demonstrate the efficacy and safety of this procedure,” he said.

However, this novel approach introduces a new way of thinking about visual rehabilitation for patients with congenital cataract. Moreover, it is also the first proof-of-concept that human tissue can be successfully regenerated in vivo by endogenous stem cells,” said Dr. Zhang, professor of ophthalmology and chief of ophthalmic genetics, University of California-San Diego.

“Since newts can regenerate their own limbs and other organs, latent regenerative capacity should exist in mammals as well,” Dr. Zhang said said. “If researchers can develop techniques for regenerating tissues and organs using endogenous stem cells, we can envision a future where there is new hope for patients surviving myocardial infarction and those living with hepatic disease, diabetes, degenerative brain diseases, and a host of other conditions.”

LECs as stem cells

The development of posterior capsule opacification (PCO) and Soemmering ring formation after cataract surgery provided the genesis for the idea of retaining LECs as a means for achieving functional lens regeneration after cataract surgery.

Lens regeneration has been contemplated for many years; however, the new approach overcomes some key difficulties.

“PCO and Soemmering ring formation are well recognized phenomena after cataract surgery and represent disorganized regrowth of LECs,” Dr. Zhang explained. “However, without an intact lens capsule and proper inductive environment, they won’t form a useful lens.

“Neverthless, these observations suggest that LECs are stem cells with proliferative potential and the ability to generate mature lens fiber cells,” Dr. Zhang said. Our hypothesis is that, given the proper environment and stimulation, we can regenerate a lens with visual function.”

Initial preclinical experiments confirmed a role for LECs in lens regeneration and showed that loss of LEC homeostasis led to cataract formation.

A look ahead

A look ahead

Despite the favorable safety and efficacy outcomes reported in the published paper, Dr. Zhang observed that the new approach does not result in generation of a perfect lens as peripheral cortical changes are seen in some cases.

In addition, it does not address certain underlying causes of cataract, such as genetic mutation, and so the potential for recurrent cataract remains.  In fact, opacification is being observed during longer follow-up that ranges up to 18 months in some cases.

“Importantly, however, the visual axis may remain clear during the critical period of vision development so that it would reduce the risk of amblyopia, and buy time while the eye develops to a point where it is possible to implant an IOL powered to provide accurate and long-lasting refractive correction,” Dr. Zhang said.

“To date, some children have undergone a second cataract surgery with IOL implantation, and they are doing well during the short-term follow-up,” Dr. Zhang said. “So, it appears there is a viable back-up plan if the cataract recurs.”

Potential for senile cataract surgery

The decision to develop a technique for promoting functional lens regeneration after congenital cataract surgery recognized limitations of the current surgical procedure for that population, both with respect to techniques used for refractive correction and visual rehabilitation and the associated risks and complications, particularly the lifelong risk of glaucoma.

Dr. Zhang said it is tantalizing to think about expanding the project to adult cataract surgery, but challenges exist.

The age-related decline in the regenerative potential of LECs is one obstacle, although Dr. Zhang suggested they are developing techniques and materials that may augment regenerative capability.

A second issue relates to the fact that adult cataract surgery is already an extremely safe and effective procedure that generally produces a rapid return of functional vision.

“Visual recovery that depends on lens regeneration might take 6 months to 1 year in adults, and so patients would need refractive correction during that period,” Dr. Zhang said. “On the other hand, lens regeneration could result in accommodation restoration, thereby providing a solution for the correction of presbyopia, and in a sense giving a young functional lens back to a patient.”

Kang Zhang, MD, PhD

E: k5zhang@ad.ucsd.edu

Dr. Zhang did not indicate a financial interest in the subject matter.