NIR-triggered thermosensitive polymer brush coating modified intraocular lens for smart prevention of posterior capsular opacification.

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. Drug-eluting intraocular lens (IOLs) is a promising concept of PCO treatment in modern cataract surgery. However, the large dose of drugs in IOL leads to uncontrollable and unpredictable drug release, which inevitably brings risks of overtreatment and ocular toxicity. Herein, a low-power NIR-triggered thermosensitive IOL named IDG@P(NIPAM-co-AA)-IOL is proposed to improve security and prevent PCO by synergetic controlled drug therapy and simultaneous photo-therapy. Thermosensitive polymer brushes Poly(N-isopropylacrylamide-co-Acrylic acid) (P(NIPAM-co-AA)) is prepared on IOL via surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization. Then, Doxorubicin (DOX) and Indocyanine green (ICG) co-loaded Gelatin NPs (IDG NPs) are loaded in P(NIPAM-co-AA) by temperature control. The IDG NPs perform in suit photodynamic & photothermal therapy (PTT&PDT), and the produced heat also provides a trigger for controllable drug therapy with a cascade effect. Such functional IOL shows excellent synergistic drug-phototherapy effect and NIR-triggered drug release behavior. And there is no obvious PCO occurrence in IDG@P(NIPAM-co-AA) IOL under NIR irradiation compared with control group. This proposed IDG@P(NIPAM-co-AA)-IOL serves as a promising platform that combines phototherapy and drug-therapy to enhance the therapeutic potential and medication safety for future clinical application of PCO treatment.

An in vitro evaluation of the Anew Zephyr open-bag IOL in the prevention of posterior capsule opacification using a human capsular bag model.

PURPOSE: During cataract surgery an IOL is placed within the capsular bag. Clinical studies show that IOLs with a square edge profile and complete contact between the IOL and the anterior capsule (AC) are currently the best way to prevent posterior capsule opacification (PCO). This has been challenged by recent clinical and experimental observations, which suggest that if the capsular bag is kept open with separation of contact between the AC and posterior capsule (PC) by an "open-bag device" PCO is dramatically reduced. Therefore, the current study set out to evaluate the putative merits of an open-bag IOL (Anew Zephyr) in a human capsular bag model. METHODS: An in vitro organ culture model using the bag-zonular-ciliary body complex isolated from fellow human donor eyes was prepared. A capsulorhexis and lens extraction were performed, and an Alcon Acrysof IOL or Anew Zephyr IOL implanted. Preparations were secured by pinning the ciliary body to a silicone ring and maintained in 6 mL Eagle's minimum essential medium (EMEM) or EMEM supplemented with 2% vol/vol human serum (HS) and 10 ng/mL TGF-ß2 for 28 days. Cell growth and capsular modifications were monitored with phase-contrast and modified dark-field microscopy. RESULTS: In serum-free EMEM culture conditions, cells were observed growing onto the PC of preparations implanted with an Anew Zephyr IOL, but this was retarded relative to observations in match-paired capsular bags implanted with an Alcon Acrysof IOL. In the case of cultures maintained in 2% HS-EMEM plus TGF-ß2, the movement on to the PC was again delayed with the presence of an Anew Zephyr IOL. Differences in the degree of growth on the PC and matrix modifications were apparent with the different donors, but in each case the match-paired Alcon Acrysof implanted bag exhibited significantly greater coverage and modification of the capsule. CONCLUSIONS: The Anew Zephyr open-bag IOL performs consistently better than the Alcon Acrysof IOL in the human capsular bag model. We propose that the benefits observed with the Anew Zephyr result from a reduction in growth factor levels available within the capsular bag and a barrier function imposed by the ring haptic.

Prevention of capsule opacification after accommodating lens refilling: pilot study of strategies evaluated in a monkey model.

PURPOSE: To test 2 strategies to prevent capsule opacification after accommodating lens refilling in a rhesus monkey model. SETTING: Animal laboratory and laboratory of European university medical centers. DESIGN: Experimental study. METHODS: Six rhesus monkeys had refilling of the lens capsular bag. In the first strategy, before it was filled with a silicone polymer, the capsular bag was treated with noncommercial sodium hyaluronate 1.0% containing cytotoxic substances. In the second strategy, the capsular bag was filled with clinically used sodium hyaluronate 1.0% (Healon) after treatment with actinomycin-D. Slitlamp inspection was performed during a follow-up of 40 to 50 weeks. After enucleation, magnetic resonance images were obtained and confocal fluorescence imaging was performed. RESULTS: Using the first strategy, capsule opacification developed in all eyes. Using the second strategy, 1 monkey did not develop capsule opacification after a 9-month follow-up. In a second monkey, the lens capsule remained clear for 3 months, after which the hyaluronate refill material was exchanged with a silicone polymer and capsule opacification developed. Combining these results with those in a previous study, the difference in opacification between silicone and sodium hyaluronate as refilling materials was statistically significant (P<.01). CONCLUSIONS: That no capsular bag fibrosis occurred in the presence of hyaluronate suggests that the properties of hyaluronate are the reason that remaining lens epithelial cells do not develop into fibrotic cells. The choice of a suitable lens-refilling material prevents the development of capsule opacification. FINANCIAL DISCLOSURE: Mr. Terwee was an employee of Abbott Medical Optics B.V. during the study period. No other author has a financial or proprietary interest in any material or method mentioned.

Effect of total lens epithelial cell destruction on intraocular lens fixation in the human capsular bag.

PURPOSE: To evaluate the effect of complete destruction of lens epithelial cells (LECs) in the capsular bag on intraocular lens (IOL) stability. SETTING: School of Biological Sciences, University of East Anglia, Norwich, United Kingdom. DESIGN: Comparative evaluation. METHODS: An in vitro organ culture model using the bag-zonule-ciliary body complex isolated from fellow human donor eyes was prepared. A capsulorhexis and fiber extraction were performed, and an Acrysof IOL was implanted. Preparations were secured by pinning the ciliary body to a silicone ring and maintaining it in 6 mL Eagle minimum essential medium supplemented with 5% v/v fetal calf serum and 10 ng/mL transforming growth factor-ß2 for 3 weeks or more. One bag of each pair was treated with 1 µM thapsigargin to destroy all LECs. Observations of LEC growth were captured by phase-contrast microscopy, IOL stability by video microscopy, and endpoint analysis through scanning electron microscopy and immunocytochemistry. RESULTS: The LECs in control capsular bags migrated centrally, closing the bag and fixating the IOL between the anterior and posterior capsules, as seen clinically. These events were not observed in the thapsigargin-treated group. After a period of controlled orbital movement, the IOL in the control group stabilized quicker than in the treated bags. There was no IOL rotation in the bag; however, the IOLs in the treated group rocked with axial movement. CONCLUSIONS: The LECs appeared to aid stabilization of current IOL designs in the capsular bag. The results have clinical implications for IOL design and for strategies to prevent posterior capsule opacification. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.