Improving Outcomes in Cataract Surgery: Intraocular Lenses (IOLs) Resistant to Cell Growth - ABSTRACT
Cataracts, a clouding of the natural lens, is the leading cause of blindness worldwide, with a projected 40M
cases by 2050. Underrepresented groups and medically underserved populations are disproportionately
impacted by cataracts. Clinical treatment is limited to surgical removal of the cataractous lens, and
implantation of an intraocular lens (IOL). Unfortunately, the IOL is highly susceptible to growth from residual
lens epithelial cells (LECs), a complication known as posterior capsule opacification (PCO) that occurs in
~40% of adult IOL patients. Laser capsulotomy surgery is used to treat PCO, but has significant potential side
effects. The proposed work will lead to the development of “LEC-resistant IOLs” based on a new amphiphilic
silicone, reducing the incidence of PCO and the need for a 2nd surgery (laser capsulotomy). This work is
significant given not only the expected exceptional LEC-resistance and retention of desired opto-mechanical
properties of the proposed IOLs (supported by preliminary data), but also that it relies on a strategy readily
integrated into existing IOL materials, designs, and manufacturing processes. Diphenyl silicones are used to
prepare foldable IOLs, wherein the elastomeric nature provides the ability to fold the IOL upon implantation
such that the incision size may be reduced. In this work, new amphiphilic surface-modifying additives (SMAs)
[developed by the PI], comprised of a poly(ethylene oxide) (PEO) segment and siloxane tether, will be readily
blended into an IOL-type diphenyl silicone. These SMAs uniquely afford rapid and substantial migration to the
aqueous/biological interface to produce LEC-resistance, without impacting opto-mechanical properties. The
innovation of this work rests not only in the novelty of the PI-developed SMAs, but in the departure from
other strategies that have attempted to produce IOLs with resistance to LEC growth (e.g., change to IOL
geometric design, complex surface treatment, and reactive oxygen species (ROS)-producing modifiers). The
approach to accomplish this work relies on a systematic and robust methods, and will be led by a team of
skilled experts. In Aim 1 [led by Grunlan, PI], silicone formulations will be prepared with SMAs of varying
structure and concentration in the diphenyl silicone, key material properties assessed, and IOLs prepared
from formulations meeting success criteria. In Aim 2 [led by Chandler, Co-I] select formulations will be
evaluated for resistance to LEC growth, and select IOLs assessed ex vivo in rabbit and human eyes with a
commercial silicone IOL used as a control. Following iterations of Aim 1 and 2, in Aim 3 [led by Scott, Co-I),
a SMA-modified IOL will be evaluated in a rabbit model, and biocompatibility and resistance to LEC growth
compared to the commercial IOL. The clinical consultant, Dr. Lee, M.D. (a comprehensive ophthalmologist
and ocular pathologist) will provide guidance to these studies.
