Assessment of intraocular lens/capsular bag biomechanical interactions following cataract surgery in a human in vitro graded culture capsular bag model

Abstract

Intraocular lenses (IOLs) are implanted during cataract surgery. For optimum results, stable positioning of the IOL in the capsular bag is important. Wound-healing events following cataract surgery lead to modification of the capsular bag and secondary visual loss due to posterior capsule opacification. At present, it is unclear how these biological events can affect stability of the IOL within the capsular bag. In the present study, a human in vitro graded culture capsular bag model was the experimental system. Capsulorhexis and lens extraction performed on human donor eyes generated suspended capsular bags (5 match-paired experiments). Preparations were secured by pinning the ciliary body to a silicone ring and maintained in 6 mL of medium for 84 days using a graded culture system: days 1-3, 5% human serum and 10 ng/mL transforming growth factor β (TGFβ2); days 4-7, 2% human serum and 1 ng/mL TGFβ2; days 8-14, 1% human serum and 0.1 ng/mL TGFβ2; days 15-84, serum-free Eagle's minimum essential medium (EMEM). A CT LUCIA 611PY IOL was implanted in all preparations. Quantitative measures were determined from whole bag images captured weekly. Images were registered using FIJI and analysed in ImageJ to determine capsular bag area; distortion; angle of contact; haptic stability; capsulorhexis area; and a fusion footprint associated with connection between the anterior and posterior capsules. Cell coverage and light scatter were quantified at end-point. The transdifferentiation marker, α-SMA was assessed by immunocytochemistry. Immediately following surgery, distortion of the capsular bag was evident, such that a long axis is generated between haptics relative to the non-haptic regions (short axis). The angle of contact between the haptics and the peripheral bag appeared inversely correlated to capsular bag area. Growth on the peripheral posterior capsule was observed 1 week after surgery and beneath the IOL within 1 month. As coverage of the posterior capsule progressed this was associated with matrix contraction/wrinkles of both the central posterior capsule and peripheral capsular bag. Cells on the central posterior capsule expressed αSMA. Fusion footprints formed in non-haptic regions of the peripheral bag and progressively increased over the culture period. Within and at the edge of the fusion footprint, refractive structures resembling lens fibre cells and Elschnig's pearls were observed. Cell attachment to the IOL was limited. An impression in the posterior capsule associated with the CT LUCIA 611PY optic edge was evident; cell density was much greater peripheral to this indent. Wound-healing events following surgery reduced capsular bag area. This was associated with the long/short axis ratio and angle of contact increasing with time. In summary, we have developed a human capsular bag model that exhibits features of fibrotic and regenerative PCO. The model permits biomechanical information to be obtained that enables better understanding of IOL characteristics in a clinically relevant biological system. Throughout culture the CT LUCIA 611PY appeared stable in its position and capsular bag modifications did not change this. We propose that the CT LUCIA 611PY optic edge shows an enhanced barrier function, which is likely to provide better PCO management in patients.

Keywords: Capsular bag; Cataract surgery; Human; In vitro; Intraocular lens; Lens; Model; Posterior capsule opacification.