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Purpose: Development of an osmotic-shock technique to remove human lens epithelial cells (LECs) as a preventive measure to address posterior capsule opacification (PCO) after pediatric cataract surgery., Setting: Department of Genetics, UCL Institute of Ophthalmology, London, England, and Department of Ophthalmology, Ruijin Hospital, Jiao Tong University, Shanghai, China., Design: Laboratory study., Methods: Various tissue preparations of human LECs (cultured on coverslips/collagen-coated membrane inserts, human lens capsule biopsies, and lens organ cultured PCO models) were subjected to a single or incremental hyperosmotic shock (NaCl, 350-4000 mOsm/L) in the presence of inhibitors of the Na + -K + -2Cl - cotransporter (NKCC) (to disable the regulatory volume increase [RVI] process). The integrity of the cell monolayer was determined by phase-contrast microscopy, viability assays, and measurement of transepithelial resistance., Results: Hyperosmotic shock (400 mOsm/L) caused rapid cell shrinkage (<5 minutes) in all the LEC models studied. In the absence of the NKCC inhibitor, the shrunk cells gradually returned to their original cell volume and architecture over time, while still exposed to the hyperosmotic shock. However, inhibition of the RVI process disabled the ability for restoration of cell volume leading to persistent cell shrinkage, subsequently resulting in cell detachment from the underlying support medium., Conclusion: Hyperosmotic shock in the presence of inhibitors of the RVI process was effective in rapidly detaching LECs from their basement membranes. This technique could potentially facilitate removal of residual LECs left on the lens capsule after cataract surgery, thus decreasing or eliminating the risk for aggressive cell proliferation and the development of PCO., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Purpose: Posterior capsule opacification (PCO) is a common complication of cataract surgery. In addition to improved surgical methods and IOL designs, it is likely additional agents will be needed to improve patient outcomes. Presently no pharmacological agent is in clinical use to prevent PCO. Here we investigate the putative ability of resveratrol (RESV), a naturally occurring polyphenol, as a therapeutic agent., Methods: The human lens epithelial cell line FHL124, a human lens capsular bag model, and central anterior epithelium were used as experimental systems. Standard culture was in 5% fetal calf serum Eagle's minimum essential medium; 10 ng/mL transforming growth factor-β2 (TGFβ2) was used to induce fibrotic changes. A scratch wound assay was used to measure cell migration and the patch assay was used to assess matrix contraction by FHL124 cells. Protein expression was assessed by immunocytochemistry and Western blot and gene expression by quantitative RT-PCR. In capsular bags, cell growth across the posterior lens capsule, capsular wrinkling, and epithelial-to-mesenchymal transition were determined by image analysis., Results: In FHL124 cells, addition of 30 μM RESV significantly impeded cell migration in a wound-healing assay. RESV significantly inhibited TGFβ2-induced expression of the myofibroblast marker alpha-smooth muscle actin (α-SMA) at both the message and protein levels, as well as significantly inhibiting matrix contraction induced by TGFβ2. In human capsular bags, 30 μM RESV significantly inhibited cell growth. TGFβ2-induced α-SMA expression and capsular wrinkling were also significantly inhibited by RESV treatment. RESV significantly suppressed expression of TGFβ2-induced genes associated with fibrotic disease, including matrix metalloproteinase-2 in FHL124 cells, capsular bags, and central anterior epithelium., Conclusions: RESV can counter PCO-related physiological events in two human lens model systems. RESV therefore has the potential to be used as a candidate agent for the prevention of PCO, which in turn could benefit millions of cataract patients.

Purpose: To analyze and compare the surface properties of commercially available hydrophobic acrylic intraocular lenses (IOLs)., Setting: Eye Clinic, University of Trieste, Italy., Design: Experimental study., Methods: The following 6 single-piece hydrophobic acrylic IOL models with the same dioptric power were studied and compared: Clareon SY60WF, Tecnis PCB00, enVista MX60, CT Lucia 601P, Vivinex iSert XY1, and iSert 251. Topography of the IOL surface was analyzed using atomic force microscopy (AFM). Surface contact angle measurements using the sessile drop method were performed to assess IOL wettability., Results: The AFM analysis showed that the Vivinex iSert XY1 IOL and Clareon SY60WF IOL had the lowest surface roughness (P < .05); there was no statistically significant difference in surface roughness between the those 2 IOL models (P > .05). Surface contact angle measurements showed that the iSert 251 IOL had the highest hydrophobicity. The CT Lucia 601P IOL had the lowest contact angle of all IOL models., Conclusions: The AFM analysis and surface contact angle measurements of all IOLs tested showed that the Vivinex iSert XY1 IOL and Clareon SY60WF IOL had the best topographic features. The smoother, more regular surface of these new IOL models might reduce cell adhesion and therefore lower the incidence of posterior capsule opacification., (Copyright © 2019 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To reduce capsular opacification by a peri-surgical treatment of the lens capsule with drugs in an in vivo rabbit model. Lens-refilling surgery is a potential therapeutic intervention to treat patients with a cataract lens. The lens material is replaced with an injectable (bio)polymer that retains the natural mechanical and optical lens properties, therewith allowing accommodation. The occurrence of capsular opacification mediated by lens epithelial cells negatively affects accommodation and vision and should be avoided in this lens restoration approach., Methods: An in vivo rabbit animal model was used with lens replacement with a silicone-based gel-like polymer and concurrent treatment of the lens epithelium with drugs. A case-study approach was applied as both drug combinations and implantation times were varied. The following drugs were investigated for their potential to prevent capsular opacification long-term: actinomycin D, methotrexate, paclitaxel and Tween-20. All were administered in a hyaluronic acid vehicle. The rabbits were clinically followed for periods up to 4 years postimplantation. Eyes, corneas and lenses were analysed post-mortem using MRI and confocal microscopy., Results: Treatment combinations containing actinomycin D generally led to the least appearance of capsular fibrosis. The use of Tween-20 or paclitaxel without actinomycin D resulted in much earlier and pronounced fibrotic responses. The aspect of capsular opacification was highly variable in individual animals. Application of the drugs in a hyaluronic acid vehicle appeared to be a safe method that spared the corneal endothelium., Conclusion: The feasibility of long-term prevention of fibrosis over a period of more than 4 years has been demonstrated in lens refilling in the rabbit model., (© 2019 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To study the effect of rotation of intraocular lens (IOL) on posterior capsular opacification (PCO) in eyes with phacoemulsification., Methods: This was a prospective, comparative, randomized case series. One eye of each patient was randomized to one of two groups. The 360-degree rotation of IOL was carried out after its placement in the capsular bag (rotation group). The control group had no rotation of IOL. PCO was analyzed by an independent observer on EPCO computer analysis system at 6, 12, 24, and 36 months., Results: The study included 50 patients (100 eyes) with senile cataracts scheduled for phacoemulsification and IOL implantation. The median age in 2 groups was 66 years. 25% quartile age in both the group was 62 years (P = 0.06). There were 30 males, and 20 females. The median PCO score at 6, 12 and 24 months was significantly low in the rotation group (0.15, 0.13, 0.22) compared to the control group (0.22, 0.23, 0.25). There was no significant difference in PCO score between the two groups from 24-36 months. The median PCO score at 36 months was 0.2 in both the groups. At the end of three years, 4 eyes (8%) in the rotation group, and 10 eyes (20%) in the control group needed Nd:YAG capsulotomy (P = 0.04)., Conclusion: Rotation of IOL in the capsular bag decreases PCO and Nd:YAG capsulotomy rate., Competing Interests: None

MicroRNAs (miRNAs) are endogenously expressed, non-coding, small RNAs which inhibit protein translation through binding to target mRNAs. Recent studies have demonstrated that miRNAs participate in the regulation of a variety of cell structures and functions including those for cell proliferation and migration. MicroRNA-34a (miR-34a), a potential effector of the p53 tumor suppressor gene, is extensively studied for its suppression of cell growth. In the present study, we investigated the function of miR-34a in human lens epithelial cells. Following confirming that miR-34a expression was increased in a P53 dependent manner in human lens epithelial cells after treatment with doxorubicin, we demonstrated that overexpression of miR-34a in the human lens epithelial cell line HLE B3 led to a significant decrease in cell proliferation and migration, with the use of MTS and transwell migration assays. Moreover, HGF enhanced the proliferation and migration of human lens epithelial cells. miR-34a was found to downregulate the expression of c-Met protein by Western blotting. Furthermore, overexpression of miR-34a downregulated the levels of phosphorylated Akt, phosphorylated ERK1/2 and other cell cycle regulators. miR-34a expression was significantly reduced in posterior capsule opacification (PCO) clinical samples. These results demonstrate that miR-34a may act as a suppressor in PCO by regulating human lens epithelial cell proliferation and migration through downregulation of c-Met., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To develop a single-piece open-capsule intraocular lens (IOL) that can be inserted through a small incision and that prevents posterior capsule opacification (PCO) by expanding the capsule and circulating aqueous humor into the capsular bag., Setting: Department of Ophthalmology, Dokkyo Medical University, Tochigi, Japan., Design: Experimental study., Method: Using the same hydrophobic acrylic material as the NY-60 IOL, a prototype open-capsule IOL was constructed. The IOL has a single optic and 2 haptics, with a 2.8 mm high spacer and holes through which aqueous humor circulates into the capsular bag by separating the anterior capsule from the posterior capsule and expanding the capsule. The open-capsule IOL or NY-60 (as a control group) was inserted in rabbit eyes. Posterior capsule opacification development was evaluated by measuring the thickness of the cell layer at the center of the posterior capsule on histopathologic specimens and statistically comparing the thickness between the open-capsule IOL group and control group., Results: The open-capsule IOL could be inserted through a 3.2 mm corneal incision using a D cartridge. The mean thickness of the cell layer at the center of the posterior capsule was 4.78 μm ± 2.61 (SD) in the open-capsule IOL group and 101.14 ± 25.19 μm in the control group and was significantly smaller in the open-capsule IOL group., Conclusion: The prototype single-piece IOL could be implanted through a small incision and prevented PCO by expanding the lens capsule and circulating aqueous humor into the capsular bag., (Copyright © 2019. Published by Elsevier Inc.)

Objective: This meta-analysis aims to evaluate the incidence of secondary glaucoma in patients under the age of 2 years who underwent congenital cataract surgery with or without primary intraocular lens (IOL) implantation., Methods: An electronic literature search was performed in Medline, EMBASE, and Web of Science databases to retrieve studies between January 2011 and November 2018. Patients with congenital cataract who did primary IOL implantation, aphakia, or secondary IOL implantation followed by receiving extraction surgery were included in this study. Relevant studies meeting defined eligibility criteria were selected and reviewed systematically by meta-analysis. Long-term incidences of secondary glaucoma, which developed at least one year after cataract surgery, were considered and discussed as clinical outcomes in each cohort. The pooled data were analyzed according to a random effects model., Results: Eight publications involving 892 eyes were included in the current meta-analysis. In the general population of eyes with congenital cataract, the long-term incidence of secondary glaucoma was lower (P = 0.06) in eyes with primary IOL (9.5%) than in eyes without primary IOL (15.1%), including aphakia and secondary IOL. The pooled risk ratio (RR) favors primary IOL implantation in all patients (RR = 0.63). For bilateral congenital cataract, the incidence was 6.7% in eyes with primary IOL implantation, which is significantly lower than the 16.7% in eyes with aphakia and secondary IOL implantation (P<0.05, RR = 0.44). However, for unilateral congenital cataract surgery, the incidence was very similar in eyes with and without primary IOL (12.4% vs 12.0%, P = 0.61, RR = 0.87)., Conclusions: In patients under 2 years of age, primary IOL implantation for bilateral congenital cataract surgery is associated with a lower risk of secondary glaucoma., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To investigate the relationship between anterior capsule polish and visual function., Methods: Data were obtained from Pubmed, Embase, Web of Science, WanFang, VIP and CNKI up to the end of May 2018, without any date or language restrictions for trials. The modified Jadad scale and the newcastle-ottawa scale were used to assess the quality of included studies. Uncorrected visual acuity (UCVA) and posterior capsule opacification (PCO) were used as outcome variables. Data on anterior capsule polish were pooled using weighted, random-effect meta-analysis., Results: One randomized controlled trial and 4 observational cohort studies involving 2533 patients were included in the analyses. There was a statistically significant difference of UCVA (OR 1.92, 95% CI 1.41-2.61) between the polish group and the control group, indicating that anterior capsule polish improved UCVA. Further studies with continuous data also suggested that anterior capsule polish was associated with good UCVA (MD 0.11, 95% CI 0.06-0.16). Posterior capsule opacification rate for 1-year or longer follow-up were extracted for 2561 eyes in 3 studies. Posterior capsule opacification rate was lower in the anterior capsule polish group according to summary odds ratio on PCO rate (OR 0.42 95% CI 0.24-0.73)., Conclusions: Anterior capsule polish prevents complication of modern cataract surgery and benefits on visual function in short term follow-up period., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Posterior capsule opacification (PCO) occurs as a common complication after cataract surgery. Erlotinib is an inhibitor of the epidermal growth factor-Receptor and reduces critical cellular events leading to PCO. In this in vitro study, Erlotinib-modified intraocular lenses (IOLs) employed as a drug delivery device have been evaluated for PCO prevention., Methods: The IC 50 concentration of Erlotinib was determined by using FHL-124 cells. For the human capsular bag model, 40 cadaver eyes underwent sham cataract surgery. Sixteen capsular bags were exposed to the IC 50 of Erlotinib. Intraocular lens (IOL) of three different materials was pharmacologically modified and tested in the anterior segment model and implanted into 24 capsular bags. To test for corneal toxicity, pairs of human cornea were exposed to high concentrations of Erlotinib and corneal endothelial cells (CEC) were exposed to the modified IOL. Release kinetics of Erlotinib from the IOL was measured., Results: IC 50 of Erlotinib was determined to be 10 μm. Erlotinib alone (p = 0.002) and when soaked into IOLs (p < 0.001) significantly increased the number of days needed until total cell coverage of the capsular bags in comparison with the control. Modified IOLs mitigated cell growth in the anterior segment model (p < 0.001). No short-term corneal toxicity was observed up to a concentration of 100 μm, and IOLs did not show toxicity on CEC. Erlotinib was released constantly from IOL., Conclusion: Erlotinib might be of clinical relevance in PCO prophylaxis, as its short-term application induces a long-term deceleration of cellular growth. Erlotinib can be introduced into the eye via soaked IOLs., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

In order to determine whether posterior capsule opacification after cataract surgery, could be delayed or inhibited through the application of hydrogen peroxide (H 2 O 2 ) or distilled water (H 2 Od),we extracted lens capsules from 25 human donor eye globes. Samples were treated for 5 min with either 30 mM H 2 O 2 or H 2 Od or used as controls, and cultured for one month, during which dark field and tilt illumination photos were taken. These were used to observe and quantify, time until cellular growth and confluence on the posterior capsule. After culture, histological sections were stained for H&E, α-SMA, Ki-67 and vimentin and evaluated. We prevented cellular growth in 50% of H 2 Od and 58% H 2 O 2 of treated samples. The overall prevention of cell growth compared to cultured controls was significant for both treatments while there was no significant difference between them. In the cases where cellular growth was not prevented, both treatments significantly delay cellular growth. Until day 28 none of the treated samples of either type that had shown growth reached total confluence. All cultured controls reached total confluence before treated samples (median = day 11.5). Also, histologically, there was a clear morphological difference between cultured controls and treated samples.

Purpose: Cataract surgery is a procedure by which the lens fiber cell mass is removed from its capsular bag and replaced with a synthetic intraocular lens. Postoperatively, remnant lens epithelial cells can undergo an aberrant wound healing response characterized by an epithelial-to-mesenchymal transition (EMT), leading to posterior capsular opacification (PCO). Aldose reductase (AR) inhibition has been shown to decrease EMT markers in cell culture models. In this study, we aim to demonstrate that AR inhibition can attenuate induction of EMT markers in an in vivo model of cataract surgery., Methods: A modified extracapsular lens extraction (ECLE) was performed on C57BL/6 wildtype, AR overexpression (AR-Tg), and AR knockout mice. Immunofluorescent staining for the myofibroblast marker α-smooth muscle actin (α-SMA), epithelial marker E-cadherin, and lens fiber cell markers αA-crystallin and Aquaporin 0 was used to characterize postoperative PCO. Quantitative reverse transcription PCR (qRT-PCR) was employed to quantify postoperative changes in α-SMA, vimentin, fibronectin, and E-cadherin. In a separate experiment, the AR inhibitor Sorbinil was applied postoperatively and qRT-PCR was used to assess changes in EMT markers., Results: Genetic AR knockout reduced ECLE-induced upregulation of α-SMA and downregulation of E-cadherin. These immunofluorescent changes were mirrored quantitatively in changes in mRNA levels. Similarly, Sorbinil blocked characteristic postoperative EMT changes in AR-Tg mice. Interestingly, genetic AR knockout did not prevent postoperative induction of the lens fiber cell markers αA-crystallin and Aquaporin 0., Conclusions: AR inhibition prevents the postoperative changes in EMT markers characteristic of PCO yet preserves the postoperative induction of lens fiber cell markers.

Background: We evaluated the long-term biocompatibility and safety of a new modular posterior chamber intraocular lens (IOL) system in rabbit eyes., Methods: Seven New Zealand rabbits underwent bilateral phacoemulsification with placement of the modular IOL in OD and a control IOL (SA60AT) in OS. Slit-lamp examinations were performed at postoperative weeks 1, 2, 3, 4, 6 and 8 and months 3 and 6. All rabbits were then sacrificed and eyes enucleated. The eyes were examined grossly from the Miyake-Apple view. Selected IOLs were explanted and underwent surface staining for implant cytology. All globes were then sectioned and processed for histopathological examination., Results: The modular IOL remained stable in all seven rabbits through the entire follow-up period. Biocompatibility was better than the control lens at six months postoperatively, on account of less extensive synechiae formation as assessed by slit-lamp examination. At the six-week examination, posterior capsule opacification (PCO) was significantly better in the test group (scored as 1.71 ± 0.8 versus 3.28 ± 0.48 in the control group, p = 0.0008). On gross examination with the Miyake-Apple view, Soemmering's ring formation was significantly better in the test group, (5.14 ± 1.57 versus 10.85 ± 1.95 in the control group, p = 0.002)., Conclusion: Previous studies showed that explantation/exchange of the modular system optic was safer and easier than with a standard IOL. The new modular IOL system has demonstrated better long-term biocompatibility compared to the control lens at six months postoperatively in the rabbit model., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Mammalian target of rapamycin (mTOR) serves a central role in regulating cell growth and survival, and has been demonstrated to be involved in the pathological progression of posterior capsule opacification (PCO). In the present study, the potency of PP242, a novel dual inhibitor of mTOR complex 1/2 (mTORC1/2), in the suppression of the growth of human lens epithelial cells (HLECs) was investigated. Using a Cell Counting Kit‑8 and a wound healing assay, it was demonstrated that PP242 inhibited the proliferation and migration of HLECs. In addition, western blot analysis indicated that PP242 completely inhibited mTORC1 and mTORC2 downstream signaling activities, whereas rapamycin only partially inhibited mTORC1 activity within LECs. Furthermore, PP242 treatment led to an upregulation of the expression levels of p53 and B cell lymphoma‑2 (Bcl‑2)‑associated X and downregulation of Bcl‑2. In addition, flow cytometric analysis demonstrated that PP242 induced the cell cycle arrest at the G0/G1 phase, which may have caused apoptosis and induced autophagy within the LECs. The results of the present study suggested that administration of PP242 may potentially offer a novel therapeutic approach for the prevention of PCO.

Purpose: To study the effect of capsular bag irrigation of trypan blue dye (0.06%) on posterior capsular opacification (PCO) in eyes undergoing phacoemulsification., Methods: This was a randomized, trial conducted at a tertiary eye care center in central India. The study included 50 patients (100 eyes) with senile cataracts who were scheduled for phacoemulsification and intraocular lens (IOL) implantation and were willing to undergo bilateral cataract surgery. One eye of each patient was randomized to one of two groups. The dye group received 0.2 ml of trypan blue injected in the capsular bag after cortical cleanup under air. The control group (other eye of the same patient) received 0.2 ml of balanced salt solution injected in a similar manner. PCO in the central 3 mm area of IOL optic was analyzed by a masked observer using an evaluation of PCO software computer analysis system at 6, 12, 24, and 36 months., Results: The average age of patients was 62.05 ± 6.22 in the dye group and 64.92 ± 7.16 years in the control group. The mean PCO score at 6 months was significantly lower in the dye group (0.10 ± 0.15) than in the control group (0.22 ± 0.30). There were no significant differences in the PCO scores between the two groups from 12 to 36 months. At the end of 3 years, eight eyes in the dye group and seven in the control group required YAG capsulotomy (P = 0.21)., Conclusion: Capsular bag irrigation of trypan blue dye decreased the PCO score at 6 months, but it had no effect at 36 months.

Background: Posterior capsular opacification (PCO) is a common long-term complication of cataract surgery. Intraocular lens design and material have been implicated in influencing the development of PCO. This study evaluated the association of hydrophobic and hydrophilic intraocular lenses on preventing PCO., Methods: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until August 3, 2016, using the following search terms: cataract, posterior capsule opacification, and intraocular lens. Eligible studies included randomized controlled trials (RCTs), retrospective, and cohort studies., Results: Eleven studies were included in the study with a total of 889 eyes/patients. The overall analysis revealed that hydrophobic intraocular lenses were associated with lower Nd:YAG laser capsulotomy rates than hydrophilic lenses [odds ratio (OR) = 0.38, 95% confidence interval (95% CI) = 0.16-0.91, P = .029]. Hydrophobic intraocular lenses were also associated with lower subjective PCO score (diff. in means: -1.32, 95% CI = -2.39 to -0.25, P = .015) and estimated PCO score (diff. in means: -2.23; 95% CI, -3.80 to -0.68, P = .005) as compared with hydrophilic lenses. Objective PCO score was similar between lens types. (diff. in means: -0.075; 95% CI, -0.18 to 0.035; P = .182). Pooled analysis found that visual acuity was similar between hydrophobic and hydrophilic intraocular lenses (diff. in means: -0.016; 95% CI, -0.041 to 0.009, P = .208)., Conclusion: In general, PCO scores and the rate of Nd:YAG laser capsulotomy were influenced by intraocular lens biomaterial. Lens made of hydrophobic biomaterial were overall superior in lowering the PCO score and the Nd:YAG laser capsulotomy rate, but not visual acuity.

Posterior capsular opacification (PCO) is a major post-operative complication of cataract surgery. Epithelial-mesenchymal transition (EMT) contributes to PCO. We previously indicated that Wnt3a induces the EMT of human lens epithelial cells (LECs) and plays an important role in the development of PCO. The present study aimed to test the potential effect of Dickkopf-1 (Dkk1) on Wnt3a-induced cell migration and the EMT of LECs and to explore possible cellular mechanisms. The secretion of Dkk1 was reduced in the rabbit PCO model, and Dkk1 injected into the eyes post-surgical manipulation prevented PCO formation. Cultured HLE-B3 cells were then transfected with Wnt3a in the presence or absence of Dkk1. Dkk1 treatment restored the epithelial phenotype and reversed the expression of EMT-associated proteins induced by Wnt3a. Dkk1 suppressed LEC migration and the expression of matrix metalloproteinase-1 (MMP-1), and the activity of MMP-2 and MMP-9. Dkk1 inhibited the nuclear accumulation of β-catenin, which is the key regulator of the canonical Wnt signaling. Our results indicate that Dkk1 inhibits Wnt3a-induced migration and the EMT of human LECs.The results contribute to the prevention of PCO formation and development., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Posterior capsule opacification (PCO) commonly develops following cataract surgery and is a wound-healing response that can ultimately lead to secondary visual loss. Improved management of this problem is required. The isothiocyanate, sulforaphane (SFN), is reported to exert cytoprotective and cytotoxic actions, and the latter may be exploited to treat/prevent PCO. SFN concentrations of 10 μM and above significantly impaired wound-healing in a human lens capsular bag model. A similar pattern of response was also seen with a human lens cell line, FHL124. SFN treatment promoted increased expression of endoplasmic reticulum (ER) stress genes, which also corresponded with protein expression. Evidence of autophagy was observed in response to SFN as determined by increased microtubule-associated protein 1A/1B-light chain 3 (LC3)-II levels and detection of autophagic vesicles. This response was disrupted by established autophagy inhibitors chloroquine and 3-MA. SFN was found to promote MAPK signaling, and inhibition of ERK activation using U0126 prevented SFN-induced LC3-II elevation and vesicle formation. SFN also significantly increased levels of reactive oxygen species. Taken together, our findings suggest that SFN is capable of reducing lens cell growth and viability and thus could serve as a putative therapeutic agent for PCO., Key Message: SFN reduces lens epithelial cell growth, migration, and viability. SFN can promote ER stress and autophagy in lens cells. SFN promotes MAPK signaling, and inhibition of MEK can suppress SFN-induced autophagy. ER stress and autophagy in lens cells are likely promoted by ROS production. SFN may help prevent posterior capsule opacification after cataract surgery.

Purpose: To objectively assess the long-term posterior capsule opacification (PCO) and neodymium-doped yttrium aluminium garnet (Nd:YAG) capsulotomy rate of a square-edge (SE) polymethylmethacrylate (PMMA) intraocular lens (IOL) modification in comparison with a round-edge (RE) PMMA IOL or an SE hydrophobic acrylic IOL (SE-Acrylic)., Design: Prospective, randomized, controlled fellow eye clinical study., Participants: Ninety-four patients scheduled for bilateral phacoemulsification had an SE-PMMA IOL implanted in 1 eye. An RE-PMMA IOL was implanted in the fellow eye in 46 patients (group A), and an SE-Acrylic IOL was implanted in the fellow eye in 48 patients (group B). Randomization was used to determine group assignment and which IOL was implanted in the first eye to undergo surgery., Methods: Evaluation of Posterior Capsule Opacification (EPCO) image analysis software was used to objectively grade PCO density from standardized, high-resolution retroillumination photographs obtained annually for the first 5 postoperative years and at year 9., Main Outcome Measures: The PCO scores and Nd:YAG capsulotomy rate., Results: Nine-year follow-up was achieved by 72% from group A and 63% from group B. In group A, the mean PCO score was significantly lower in the SE-PMMA IOL eyes compared with the contralateral RE-PMMA eyes at all follow-up visits (P < 0.05). In group B, the mean PCO score was statistically lower in the SE-PMMA IOL eyes compared with the contralateral SE-Acrylic IOL eyes at all but the 1- and 3-year follow-up visits. Nine-year Nd:YAG capsulotomy rates were 2% for SE-PMMA IOLs versus 37% for RE-PMMA IOLs in group A (P < 0.001), and 4% for SE-PMMA IOLs versus 10% for SE-Acrylic IOLs in group B (P = 0.435). The RE-PMMA PCO rate did not plateau and continued to increase throughout the 9-year study period., Conclusions: This prospective, 9-year fellow eye comparison study suggests that an inexpensive PMMA IOL design modification-a squared optic edge-could significantly reduce the burden of vision-impairing secondary membrane in developing countries., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To moderate the capsular opacification (CO) response after lens surgery, an experimental study was performed in which nanofibre-based hydrogels (nanogels) with different ratios of attached peptides were applied to provide extracellular matrix-related cues for lens epithelial cells (LECs) in a porcine eye model., Methods: The lens content was removed, and the capsules were refilled with nanogel. Lenses were divided into two groups, the first group (n = 34) was refilled with nanogels containing different ratios of two laminin-derived peptides (IKVAV + YIGSR), and the latter group (n = 26) was refilled with nanogel combinations of a fibronectin-derived and a type IV collagen-derived peptide (RGDS + DGEA). Two lenses were refilled with culture medium to investigate the effect of the medium on LECs. After refilling, lenses were extracted and cultured for 3 weeks. Lens epithelial cells (LECs) were assessed for morphology and alpha-smooth muscle actin (αSMA) expression using confocal laser scanning microscopy., Results: Differences were seen in cell morphology between lenses refilled with nanogels with IKVAV + YIGSR and RGDS + DGEA peptides. In nanogels with IKVAV + YIGSR peptides, differences in LEC morphology were largest when ratios between the peptides were unequal, whereas LEC responses from the RGDS + DGEA refilled groups showed variation in LEC morphology dependent on the total quantity of mixed-in peptides. The culture medium did not induce proliferation or transformation of LECs., Conclusions: Ratios and concentrations of cell adhesion-mediating peptides both can direct the LEC response, depending on the adhesion molecules of origin, by influencing LEC proliferation and transformation. Nanogels with incorporated peptides may be tuned towards CO prevention., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Posterior capsular opacification (PCO) is a common complication in cataract surgery. The development of PCO is attributed to the combination of adhesion, migration, proliferation, and transdifferentiation of the residual lens epithelial cells (LEC) onto the interface of intraocular lens (IOL) material and lens posterior, in which the initial adhesion is the beginning step and plays important roles. In the present study, hydrophilic polyethylene glycol (PEG) was immobilized onto IOL surface via plasma-aided chemical grafting procedure. The attenuated total reflection - Fourier transform infrared (ATR-FTIR) and contact angle (CA) - measurements indicate the successful surface PEGylation, as well as the excellent hydrophilicity of the surfaces. Compared with pristine IOL, the PEGylation does not influent its optical property, whereas the initial adhesion of LEC is greatly inhibited. In vivo ocular implantation results show that the PEGylated IOL presents good in vivo biocompatibility, and can effectively prevent the PCO development., (© The Author(s) 2016.)

One of the most important and challenging goals in pharmaceutical prevention for posterior capsule opacification is to preserve an effective drug concentration in capsular bag for a long period without affecting the patients' vision. Here, a novel kind of composite, which was prepared by 2-hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) via a two-step process, was applied for capsular tension ring (CTR) as an implant that could deliver docetaxel (DTX) over a long period of time. The drug release rate of the composite could be controlled by the ethyleneglycol dimethacrylate (EGDMA) content and the ratio of HEMA/MMA as well as the structure of porous PMMA framework. The CTR could continuously release DTX for up to 6 weeks in vitro and maintain DTX in effective concentration in the aqueous humor after 42 days. Docetaxel-load capsular tension ring (DTX-CTR) presented strong inhibition on the lens epithelial cells in-vivo without obvious damage to normal tissues. These results indicate that the drug sustained-release CTR can provide a promising application in posterior capsule opacification prevention., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Unlabelled: Postoperative capsule opacification is a multifactorial physiological consequence of cataract surgery that remains the most common complication of this procedure. A literature review that included several intraocular lenses (IOLs) and endocapsular devices studied in our laboratory found that devices maintaining the capsular bag in an open or expanded state were associated with improved bag clarity. This observed effect likely occurs secondary to the complex interactions of myriad mechanisms, which include formation of a barrier to lens epithelial cell (LEC) migration, mechanical compression of residual LECs, mechanical stretch at the level of the capsule equator, maintenance of overall bag contour, and enhanced endocapsular circulation of aqueous humor. We review the designs of endocapsular devices and IOLs that minimize the degree of postoperative capsule opacification by preventing capsular bag collapse and discuss the underlying mechanisms that contribute to this phenomenon., Financial Disclosure: None of the authors has a financial or proprietary interest in any material or method mentioned., (Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Posterior capsule opacification (PCO) is one of the main reasons for loss of vision again after cataract surgery. In this study, intraocular lenses were modified with indocyanine green (ICG) and sealed up with PLGA to form long-term intraocular implants (ICG-IOL). When triggered by laser, ICG-IOL would induce photodynamic therapy (PDT). In-vitro cell viability assay and scratch wound healing assay demonstrated that ICG-IOL could effectively inhibit HLEpiC proliferation and migration without causing damage to the cells far away from it. Laser attenuation test indicated that ICG-IOL could be applied in vivo. In-vivo pharmacodynamics and safety study showed that ICG-IOL could significantly prevent the occurrence of PCO and was safe for intraocular normal tissue. All these results suggested that ICG-IOL would be a very promising candidate for PCO prevention., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To investigate the safety and efficacy of cyclosporine A sustained release from modified intraocular lens for preventing posterior capsular opacification (PCO) in rabbit eyes., Methods: Forty-five New Zealand albino rabbits undergoing phacoemulsification in their right eyes were randomly and equally divided into three groups. Group A had implanted original IOL, group B had implanted PLGA-IOL(IOL coated with polylactide-glycoli acid), and group C had implanted CsA-PLGA-IOL (CsA loaded PLGA-IOL). All the 45 eyes were examined by a slit-lamp microscope. The intraocular pressures were recorded. Anterior chamber flare and aqueous humor cells were graded at different time point after surgery. The concentrations of CsA in the aqueous humor and blood were determined by high performance liquid chromatography. Anterior segment tissue was histologically examined. Wet posterior capsules were weighed. PCO was graded 6 months later., Results: The mean concentrations of CsA in group C at 2 h,1 d,3 d,7 d,14 d,30 d,60 d after operation were (11.47±2.42) mg/L, (10.30±2.15) mg/L, (6.71±1.45) mg/L, (4.81±1.16) mg/L, (6.11±0.84) mg/L, (2.53±0.77) mg/L, (0.86±0.28) mg/L. The concentrations of CsA in blood were undetectable. During the early days after operation, the reactions of the anterior chamber in group A and B were more severe than group C. The initial appearance of PCO in group C was much later than in the other two groups, and the grade of PCO in group C was much lower than the other two groups. The mean weights of wet posterior capsules in group A(312.86±52.91) mg and B(310.64±62.42) mg were much heavier than that of group C(56.93 ± 24.24) mg. Histological observation showed that there was remarkably less accumulation of lens materials on the posterior capsules in group C than in the other two groups. No toxic actions were found in intraocular tissues in group C., Conclusion: Our study suggested that Cyclosporin A modified intraocular lens could effectively and safely prevent the formation and development of posterior capsular opacification in rabbit eyes for a relatively long term.

Nanofiber-based hydrogels (nanogels) with different, covalently bound peptides were used as an extracellular environment for lens epithelial cells (LECs) in order to modulate the capsular opacification (CO) response after lens surgery in a porcine eye model. Lenses were divided into 15 groups (n = 4 per group), the lens content was removed and the empty capsules were refilled with nanogel without peptides and nanogels with 13 combinations of 5 different peptides: two laminin-derived, two fibronectin-derived, and one collagen IV-derived peptide representing cell adhesion motifs. A control group of 4 lenses was refilled with hyaluronan. After refilling, lenses were extracted from the porcine eye and cultured for three weeks. LECs were assessed for morphology and alpha smooth muscle actin (αSMA) expression using confocal laser scanning microscopy. Compared to hyaluronan controls, lenses filled with nanogel had less CO formation, indicated by a lower αSMA expression (P = 0.004). Microscopy showed differences in morphological cell response within the nanogel refilled groups. αSMA expression in these groups was highest in lenses refilled with nanogel without peptides (9.54 ± 11.29%). Overall, LEC transformation is reduced by the presence of nanogels and the response is improved even further by incorporation of extracellular matrix peptides representing adhesion motifs. Thus, nanomaterials targeting biological pathways, in our case interactions with integrin signaling, are a promising avenue toward reduction of CO. Further research is needed to optimize nanogel-peptide combinations that fully prevent CO., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the efficacy of a laser photolysis (LP) system in preventing posterior capsule opacification (PCO) in a human ex vivo PCO model., Setting: Ars Ophthalmica Study Center, Department of Ophthalmology, General Hospital Linz, Medical Faculty of Johannes Kepler University, Linz, Austria, and the Department of Ophthalmology, Ludwig-Maximillians-University, Munich, Germany., Design: Prospective randomized controlled laboratory trial., Methods: Open sky extracapsular cataract extraction following implantation of a capsular tension ring (CTR) into the capsular bag was performed in 28 human donor eyes. Donor eyes received LP treatment of the capsular bag fornix and the anterior capsule for 180 or 360 degrees, whereas the contralateral eyes served as a control group. Lens epithelial cell (LEC) growth onto the posterior capsule was determined objectively during 3 months of organ culture incubation., Results: The mean interval until a complete monolayer of LECs on the posterior capsule had formed was 8.2 days ± 1.2 (SD) for control eyes and 9.4 days ± 1.1 for eyes with 180-degree LP treatment (P = .042). Eyes with 360-degree treatment showed no sign of LEC growth or migration onto the posterior capsule during the entire observation period. Transmission light microscopy revealed many residual LECs on the anterior lens capsule of untreated areas, whereas no evidence of remaining LEC in areas treated with LP was found., Conclusions: This study demonstrates complete and sustained PCO prevention by a prototype LP system in a capsular tension ring-based human ex vivo model. Laser capsule polishing has the potential to serve as a successful surgical strategy for PCO prevention., Financial Disclosure: The authors have no proprietary or financial interest in any of the materials or equipment mentioned in this study., (Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the effect of disintegrin echistatin on integrin linked kinase (ILK) and subsequent PI3-K/Akt and ERK1/2 signaling pathways in the posterior capsule opacification (PCO) model of diabetic rabbit., Methods: 56 rabbits were injected alloxan to model diabetic. Then they accepted lens extraction surgery and randomly and intraoperatively injected distilled water (control group; n = 28) or 10.0 mg·L(-1) echistatin (echistatin-treated group; n = 28) into the anterior chamber. Each group was subdivided into ten days group (n = 14) and six weeks group (n = 14) respectively. The PCO severity was evaluated with a slit lamp microscope and light microscope for 10 days and 6 weeks postoperatively. The levels of ILK in the posterior capsule were determined by Q-PCR, Western blotting and Immunohistochemistry. Akt and ERK1/2 phosphorylation were analyzed by Western blotting., Results: 10 days and 6 weeks after surgery, the grades of PCO in the echistatin-treated group were lower than the control group. The lens epithelial cells (LECs) in the posterior capsule of echistatin-treated eyes had decreased degrees of proliferation and migration than the control group. And no significant side effects appeared after treated with echistatin. Echistatin could significantly reduce the expression of ILK in terms of both mRNA and protein levels. The phosphorylation levels of Akt and ERK1/2 were decreased in the echistatin-treated group compared with the control group., Conclusions: Echistatin could inhibit postoperative PCO occurrence and development in diabetic rabbit eyes, which may be related to down-regulation the expression of ILK and inhibition the PI3-K/Akt and ERK1/2 pathways.

Purpose: To determine the incidence of rhegmatogenous retinal detachment (RRD) and associated risk factors after phacoemulsification and bag-in-the-lens intraocular lens (IOL) implantation., Setting: Antwerp University Hospital, Department of Ophthalmology, Antwerp, Belgium., Design: Prospective cohort study., Methods: All consecutive bag-in-the-lens IOL implantations performed between January 2001 and December 2007 were included, with the exception of combined procedures and IOL exchanges. The retinal detachment (RD) incidence was studied in the total cohort, in a subgroup of patients with 1 to 5 years of follow-up, and finally in the group remaining after exclusion of all risk factors except gender., Results: RD after bag-in-the-lens IOL implantation in 1323 eyes with an average follow-up of 44.75 months (range 0 to 152 months) was found in 19 eyes (1.44%). The 1-year RD incidence was 0.49% (5 RD cases in 1024 eyes) (0.00% in patients without risk factors). The 2-year cumulative RD incidence was 0.84% (9 RD cases in 931 eyes; 0.15% without risk factors). Four clinically significant risk factors were confirmed: male gender, young age at time of surgery (<60 years), axial myopia (axial length ≥25 mm), and history of contralateral RD in the total cohort., Conclusion: The RRD incidence following bag-in-the-lens IOL implantation was comparable to that seen after lens-in-the-bag (LIB) implantation. The wide variation in study design in the literature precludes direct comparison, so there is a need for standardization in evaluating RRD incidence after cataract surgery. Future prospective studies should consider patients with and without risk factors (except gender) separately., Financial Disclosure: Prof. dr. M.J. Tassignon has intellectual property rights to the bag-in-the-lens intraocular lens (U.S. patent 6 027 531; EU patent 009406794; PCT/120268), which is licensed to Morcher GmbH, Stuttgart, Germany., (Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Background: Incorrect lens power remains one of the most common reasons for intraocular lens explantation/exchange. We evaluated stability and effect on capsular bag opacification of a new foldable modular lens system, with a base component and an optic component in rabbit eyes., Methods: Bilateral phacoemulsification was performed on six rabbits; one eye received the test lens (Harmoni Modular Lens, ClarVista Medical), whereas the other received a single-piece hydrophobic acrylic control lens (SA60AT, Alcon). Slit-lamp examinations were performed at postoperative weeks 1, 2, 3, 4 and 6. All rabbits were sacrificed at week 6. After enucleation, the eyes were examined grossly from the Miyake-Apple view. Following, all globes were sectioned and processed for histopathological examination., Results: The modular lens was stable in all six rabbits. Uveal biocompatibility was similar to or better in the test eyes when compared with control eyes up to 6 weeks postoperatively. Overall, capsular bag opacification was found to be significantly lower in the test eyes when compared with control eyes. At the 6-week gross examination, central posterior capsule opacification was scored as 0.58 ± 0.73 in the test group, and as 3.00 ± 1.26 in the control group (paired two samples for means t-test; two-tail P = 0.005)., Conclusions: The Harmoni Modular system remains stable within the capsular bag after implantation. Due to the design of the base component featuring long loops, along with peripheral anterior and posterior square edges, the lens appeared to prevent overall capsular bag opacification in the rabbit model., (© 2015 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To determine the structural characteristics of lens epithelial cells (LECs) found on the anterior portion of the lens capsule and their pluripotency, proliferating and migrating potential when grown ex vivo with relevance to posterior capsular opacification (PCO) after cataract surgery., Methods: The explants of anterior portion of the lens capsule consisting of monolayer of LECs were obtained from uneventful cataract surgery and were cultivated under adherent conditions. The size and shape of the outgrowing cells were recorded by scanning electron microscopy (SEM), while their migration and proliferation potential were followed using light microscopy. Positivity for proliferation (Ki-67)- and pluripotency (Sox2)-specific markers were tested by immunofluorescent staining., Results: The proliferation and migration of anterior portion of the lens capsule's LECs filling up the denuded and reverse side regions of the lens capsule as well as their growth on glass culture surfaces could be followed by light microscopy and SEM, while the distribution of LECs and their morphology could be analysed in detail by SEM. The expression of Ki-67 and Sox2 in LECs growing adherently on human anterior portion of the lens capsule could also be detected., Conclusions: Classic light microscopy and SEM can be used to show that human anterior portion of the lens capsule harbours LECs that can proliferate and migrate, suggesting their pluripotency or putative stem cell nature. Similarly, morphological techniques can be used to study PCO and the effect different drugs or physical treatments have against PCO development., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the stability and capsular bag opacification of a smooth or a patterned silicone protective membrane implanted in the bag with secondary placement of an intraocular lens (IOL)., Setting: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA., Design: Experimental study., Methods: Twelve New Zealand rabbits had bilateral implantation of a protective membrane and an IOL or an IOL alone. Three groups of 8 eyes each received the IOL and the smooth protective membrane, the IOL and the patterned membrane, or the IOL alone. Slitlamp examination was performed weekly for 4 weeks. The rabbits were then humanely killed and their globes enucleated. Capsular bag opacification was scored based on the Miyake-Apple view, and the eyes underwent histopathology., Results: At 4 weeks, the mean central posterior capsule opacification (PCO) score was 0.28 ± 0.32 (SD) in all eyes with a protective membrane and 2.08 ± 1.28 in eyes with the IOL alone (P < .00001, Student t test). Peripheral PCO and Soemmerring ring formation were also significantly less in eyes with the protective membrane. Histopathologically, the posterior capsules were relatively clear in most IOLs with the protective membrane. The smooth and patterned protective membranes showed a significant difference in overall capsular bag opacification formation compared with the IOLs without the membrane., Conclusions: The circular geometry of the protective membrane led to expansion of the capsular bag and appeared to prevent capsular bag opacification. Further studies are warranted to assess whether the pattern on the device's posterior surface further enhances this effect., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: We define the ideal anterior capsulotomy through consideration of capsular histology and biomechanics. Desirable qualities include preventing posterior capsular opacification (PCO), maintaining effective lens position (ELP) and optimising capsular strength., Methods: Laboratory study of capsular biomechanics and literature review of histology and published clinical results., Results: Parameters of ideal capsulotomy construction include complete overlap of the intraocular lens to prevent PCO, centration on the clinical approximation of the optical axis of the lens to ensure concentricity with the capsule equator, and maximal capsular thickness at the capsulotomy edge to maintain integrity., Conclusions: Constructing the capsulotomy centred on the clinical approximation of the optical axis of the lens with diameter 5.25 mm optimises prevention of PCO, consistency of ELP and capsular strength., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Posterior capsular opacification (PCO) is a common complication of cataract surgery. The development of PCO is due to a combination of the processes of proliferation, migration, and transdifferentiation of residual lens epithelial cells (LECs) on the lens capsule. In the past decades, various forms of PCO prevention have been examined, including adjustments of techniques and intraocular lens materials, pharmacological treatments, and prevention by interfering with biological processes in LECs. The only method so far that seems effective is the implantation of an intraocular lens with sharp edged optics to mechanically prevent PCO formation. In this review, current knowledge of the prevention of PCO will be described. We illustrate the biological pathways underlying PCO formation and the various approaches to interfere with the biological processes to prevent PCO. In this type of prevention, the use of nanotechnological advances can play a role., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To determine whether erufosine alone or erufosine-loaded intraocular lenses (IOLs) can inhibit growth of human lens epithelial cells after a single administration in the human capsular bag model., Setting: Laboratory for Cell Biology, Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany., Design: Experimental study., Methods: Sixteen human cadaver eyes had sham cataract surgery. The capsular bag was transferred into cell culture. The tissue was exposed to the half maximum inhibitory concentrations of erufosine alone for 72 hours; solvent-only tissue served as a control. Erufosine is a potent inhibitor of phosphoinositide-3-kinase, a downstream kinase with major implications in posterior capsule opacification (PCO) pathogenesis. The IOLs were soaked with erufosine and implanted in the capsular bags; unsoaked IOLs served as controls. For both settings, the time until confluence of the capsular bag was measured. Cell growth was observed and photodocumented., Results: Erufosine as a single therapeutic agent increased the time until confluence of the capsular bag, but not significantly compared with the control. When IOLs were soaked with erufosine, a long-term prophylactic effect was observed in this organ model for PCO, which is known to closely reflect the clinical situation., Conclusion: Erufosine-soaked IOLs effectively inhibited PCO formation as seen in long-term organ culture and might become of clinical relevance., Financial Disclosures: Drs. Kampik and Eibl-Lindner are inventors of IOLs treated with alkylphosphocholines for pharmacological after-cataract prophylaxis, patent international application PCT/EP2010/051490. No other author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to determine the Cyclosporine A (CsA) dose and minimum drug delivery time needed to prevent posterior capsule opacification (PCO) in an ex vivo canine model and evaluate the mechanism of CsA-induced cell death. Canine lens epithelial cells (LEC) were treated with CsA and changes in cell migration, proliferation, and density were monitored over time. CsA-treated LEC underwent transmission electron microscopy (TEM), immunofluorescence, and immunoblotting in the presence or absence of autophagy inhibitors to evaluate the mechanism of cell death. Lens capsules were harvested from canine cadaver eyes for an ex vivo model of PCO. Lens capsules were treated with CsA for 1, 2, 3, 4, 5, 6, or 7 days, and subsequently maintained in culture for a total of 28 days in the absence of drug. CsA reduced LEC viability in a dose dependent manner. Morphologically, CsA-treated LEC were swollen, had intact nuclei, lacked peripheral chromatin condensation, and demonstrated prominent vacuolization; TEM revealed autophagosomes. LC3-II protein expression and acridine orange fluorescence increased in CsA-treated cells. A small non-significant induction of cleaved caspase-3 was observed in CsA-treated LEC. Lens capsules treated with 5, 6, or 7 days of 10 μg/mL CsA showed a significant decrease in ex vivo PCO formation; 6 days of drug delivery prevented PCO. This study finds that morphologic changes, formation of acidic vesicles, and increased expression of LC3-II supports the hypothesis that CsA mediates LEC death via autophagy; this is a novel finding in the lens. Induction of CsA-induced apoptosis was minimal. Six days of intracapsular CsA drug delivery prevented ex vivo PCO formation., (Published by Elsevier Ltd.)

Purpose: To evaluate a single-piece hydrophobic acrylic intraocular lens (IOL) with ultraviolet-ozone (UV-O3) treatment on the posterior surface and compare it with an identical untreated IOL in a rabbit model., Setting: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA., Design: Experimental study., Methods: Study IOLs were implanted in the right eyes and control IOLs in the left eyes of 10 New Zealand rabbits. Slitlamp examinations were performed 1 to 6 weeks postoperatively. Neodymium:YAG (Nd:YAG) posterior capsulotomy was performed in both eyes of 5 rabbits after the 4-week slitlamp examination. At 6 weeks, the rabbits were killed humanely and their globes were enucleated. Capsular bag opacification was scored from the posterior aspect (Miyake-Apple view), and the eyes were processed for histopathology., Results: At 4 weeks, the mean posterior capsule opacification (PCO) scores were 0.88 ± 0.33 (SD) in the study eyes and 2.55 ± 1.13 in the control eyes (P=.003, 2-tailed paired t test). Performance of Nd:YAG posterior capsulotomy was similar in both groups. Gross postmortem examination also showed statistically less peripheral PCO in eyes with the study IOLs than in control eyes. There was no difference in histopathologic findings between study eyes and control eyes and no signs of untoward inflammation or toxicity in any eye evaluated., Conclusions: Treatment of the posterior surface of a single-piece hydrophobic acrylic IOL with UV-O3 appears to prevent PCO, likely by increasing adhesion between the posterior capsule and the IOL while retaining uveal biocompatibility. Performance of Nd:YAG posterior capsulotomy was similar between treated IOLs and untreated IOLs., (Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Accommodation may be restored to presbyopic lenses by refilling the lens capsular bag with a soft polymer. After this accommodative lens refilling prevention of capsular opacification is a requirement, since capsular opacification leads to a decreased clarity of the refilled lens. It has been hypothesized that capsular fibrosis causing the capsular opacification results in increased stiffness of the lens capsular bag, therewith contributing to a decrease in accommodative amplitude of the lens. However, the change in viscoelastic properties of refilled lenses due to capsular fibrosis has never been measured directly. In this study we examined natural lenses from enucleated porcine eyes and refilled lenses directly after refilling and after three months of culturing, when capsular fibrosis had developed, and determined their viscoelastic properties with a low load compression tester. Control refilled lenses were included in which capsular opacification was prevented by treatment with actinomycin D. We related lens stiffening to the degree of capsular opacification, as derived from the microscopic images taken with a confocal laser scanning microscope. Overall, the refilled lenses directly after refilling were softer than refilled lenses after three months of culturing, and refilled lenses treated with actinomycin D were softer compared with untreated refilled lenses. The degree of capsular opacification as assessed by microscopy corresponds to an increase in lens stiffness. This indicates that the viscoelastic properties of the refilled lens are influenced by capsular fibrosis and modulated by treatment of the lens epithelium. In conclusion, this study shows that the development of capsular fibrosis negatively affects the viscoelastic properties of isolated, cultured refilled lenses., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Posterior capsule opacification (PCO) occurs as a common complication after cataract surgery. Gefitinib is a selective inhibitor of the epidermal growth factor receptor (EGFR) which represents a potential pharmacological target for PCO prevention. In this in vitro study, we assessed the effect and biocompatibility of Gefitinib in PCO prophylaxis., Methods: The effect of Gefitinib on the key pathological features of PCO was assessed in vitro. We determined growth in the human capsular bag model, prepared from sixteen cadaver eyes that underwent sham cataract surgery. Furthermore, two lens epithelial cell lines, HLE-B3 and FHL-124, were used to determine concentration-based effects on cell proliferation. In addition, cell-migration, matrix-contraction, and cell spreading were investigated. To exclude toxic concentrations, Gefitinib was assessed for its biocompatibility on six different human ocular cell types from the anterior and posterior segment of the eye., Results: Gefitinib significantly increased the time until confluence of the capsular bag compared to controls (p < 0.001)). In both human lens epithelial cell lines (HLE-B3 and FHL-124), proliferation decreased significantly and as equally strong after incubation with Gefitinib (p < 0.001), as did chemotactic migration (p = 0.004), matrix contraction (p = 0.001), and cell-spreading (p = 0.001). At the IC50 concentration, Gefitinib was well tolerated by six different human ocular cell types of the anterior and posterior segment., Conclusion: The specific EGFR inhibitor Gefitinib might become of clinical relevance in PCO prophylaxis as it attenuated cellular growth and other pathological PCO factors in the ex vivo human capsular bag model and in two human lens epithelial cell lines, while showing good biocompatibility in vitro.

Background: To evaluate lens epithelial cell (LEC) proliferation with two different designs (one-piece or three-piece) of hydrophobic acrylic IOLs with 360° square optic edge using an in vitro culture model of posterior capsule opacification (PCO)., Methods: This experimental study was conducted at the Department of NEUROFARBA, Section of Pharmacology, University of Florence, Italy. Human LECs were seeded and cultured in transwell cell culture inserts coated with a type-IV collagen membrane on which an IOL (one-piece Tecnis-1 or three-piece AR40E, Abbott Medical Optics Inc.) had been previously placed. As control, cells were plated on the insert membrane without an IOL. At day six (cells confluent in controls) IOLs were removed and cell counting, viability and cell density under and outside the IOLs were evaluated., Results: No statistically significant difference in the number of cells (p>0.05) between inserts with the one-piece and three-piece IOLs was found. Cell density in the area under each IOL was significantly lower than in the area outside of it (p<0.05), or in the control insert. (p<0.05). Cell density under the single-piece IOL was not significantly different from that under the three-piece IOL (p>0.05)., Conclusions: A 360° sharp-edge played a crucial role in avoiding LEC migration under the IOL and preventing the formation of PCO after cataract surgery. Long term clinical evaluation is necessary to estimate functional results.

Posterior capsule opacification (PCO) is the most common complication after cataract surgery, with an incidence of 30%. It tends to be considered a normal event in the natural history of cataract surgery. Better understanding of its pathophysiology and advancement of intraocular lens material and design along with the improvement of phacoemulsification technique have contributed to decrease the incidence of PCO. Although treatment by Nd: YAG laser posterior capsulotomy is quick and non-invasive, the opening of the posterior capsule may be associated with numerous complications. Prevention remains the best measure for controlling this pathology., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Purpose: To evaluate long-term uveal and capsular biocompatibility of a new accommodating intraocular lens (IOL)., Setting: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA., Design: Experimental study., Methods: Bilateral phacoemulsification was performed in 14 rabbits; 1 eye received the accommodating IOL (Fluidvision) and the other received a hydrophobic acrylic control IOL. Slitlamp examinations were performed at postoperative weeks 1 to 4 and months 2, 3, 4, and 6. Six rabbits were humanely killed at 2 months and 8 rabbits at 6 months. After gross examination with the Miyake-Apple view, selected IOLs were removed for implant cytology. All globes were then sectioned and processed for histopathologic examination., Results: Uveal biocompatibility of study and control IOLs was similar in clinical and pathologic examinations up to 6 months postoperatively. In the study group, anterior capsule opacification appeared absent and posterior capsule opacification (PCO) was significantly less than in the control group. At the gross examination at 6 months, central PCO was 0.8 ± 0.5 (SD) in the study IOLs and 3.7 ± 0.4 in the control IOLs (P < .0001, 2-tailed paired t test). Histopathologic examination confirmed the relative lack of capsule opacification in study eyes compared with controls and the absence of untoward inflammatory reaction or toxicity in all eyes., Conclusions: The accommodating IOL maintained an expanded capsular bag secondary to the large size of the haptic elements without significant contact with the anterior capsule. This appeared to prevent overall capsular bag opacification and to retain uveal and capsular biocompatibility., (Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy of a large capsulorhexis and intraocular lens (IOL) in obtaining a larger anterior capsule opening after cataract surgery in patients with diabetes mellitus (DM)., Setting: Department of Ophthalmology, University of Fukui, Fukui, Japan., Design: Prospective clinical trial., Methods: Patients with DM had bilateral cataract surgery with a 2.8 or 3.0 mm scleral incision, a capsulorhexis with a diameter of approximately 5.0 or 6.0 mm, and implantation of a 6.0 mm optic (Eternity X-60) or 7.0 mm optic (Eternity X-70) IOL. The anterior capsule opening area, aqueous flare intensity, surgically induced astigmatism (SIA), corneal endothelial cell density (ECD), and central corneal thickness (CCT) were measured 1 day, 1 week, and 1, 3, and 6 months after surgery., Results: Thirty-one patients (62 eyes) with DM were enrolled. At all postoperative timepoints, the anterior capsule opening was significantly larger in eyes with the 7.0 mm optic IOL than in eyes with the 6.0 mm optic IOL (P<.05, Mann-Whitney U test). There were no significant differences in postoperative aqueous flare intensity, SIA, ECD, or CCT based on the size of the capsulorhexis and IOL., Conclusion: A larger capsulorhexis and implantation of a 7.0 mm IOL resulted in a larger anterior capsule opening after cataract surgery in patients with DM., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Visual axis opacification (VAO) occurs in up to 40% of pediatric patients after cataract surgery withintraocular lens implantation(IOL) even with a primary posterior capsulotomy (PPC). In both children and adult group, opacification does obscure the visual axis. However, in children after PPC, there is no capsule. Hence, the terminology VAO is used in children rather than posterior capsular opacification. This opacification is caused by a proliferation of epithelial cells on the posterior capsule or anterior vitreous face and can hinder the optical image quality needed for normal visual development. The rate of epithelial mitotic activity is higher in children compared to adult. It can be managed by Yag laser or surgical membranectomy, the latter is preferable. International and national published articles were systematically reviewed on aetio-pathogenesis, surgical techniques and equipment, type and material of IOL, and management of VAO in children operated for cataract. Author's experience was also included to write manuscript. VAO is frequent complication following cataract surgery in pediatric patients. Age of cataract patients, surgical technique and type and materials of IOL are most common influencing factor for VAO. Immediate management with advance equipment of VAO reduces the incidence for development of irreversible stimulation deprivation amblyopia.

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-β2 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-β2, 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., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

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., (Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the intra-operative and postoperative outcome of paediatric cataract surgery with primary posterior capsulotomy (PPC) and anterior vitrectomy using intra-operative preservative-free triamcinolone acetonide., Methods: In this prospective, interventional case-control study, 20 Children who underwent cataract surgery for both eyes were enrolled and their eyes were randomized into two groups. Group A consists of 20 eyes in which standard phacoaspiration with PPC with intracameral triamcinolone was used, and Group B consists of 20 eyes in which triamcinolone were not used. Intra-operative complications and postoperative outcome like intraocular pressure (IOP), posterior synechiae, pigment deposits and posterior capsule opacification (PCO) were studied., Results: In both groups, age range varied between 2-8 years comprising 18 males and two females. The mean postoperative IOP did not show any significant variation during 6-month follow-up. In study group, all the 20 eyes were quiet at 2 weeks, while there was cellular reaction 1+ in four eyes (20%) and nil in 16 eyes (80%) at 2 week in the control group (p = 0.035). Pigment deposits on IOL optic was seen in two eyes (10%) of the study group while in control group, IOL deposits were present in 14 eyes (70%) (p = 0.001). Posterior capsule opacification was seen in two eyes (10%) in control group at 3 months while none occurred in study group., Conclusions: Intra-operative use of preservative-free triamcinolone acetonide led to less anterior chamber inflammation and pigment deposits on IOL optic postoperatively compared to those eyes where it was not used., (© 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Posterior capsule opacification (PCO) after cataract surgery is due in part to proliferation of the adhering lens epithelial cells and transdifferentiation into mesenchymal cells. The histone deacetylase (HDAC) inhibitors, trichostatin A (TSA) and vorinostat (suberoylanilidehydroxamic acid [SAHA]) are known to modulate cell proliferation and epithelial-mesenchymal transition (EMT). Studies have shown that TGFβ2 can induce EMT similar to that seen during PCO. This study evaluated the effects of TSA and SAHA on TGFβ2-induced EMT in lens epithelial explants., Methods: Epithelial cells adherent to lens capsules were isolated from fresh pig lenses and human donor lenses and cultured for 12 hours. Explants were pretreated with TSA or SAHA for 1 hour and then treated with TGFβ2 for up to 3 days. Scratch wound healing assay was used to determine epithelial cell proliferation and migration in the samples. The effects of TSA and SAHA on histone acetylation and HDAC 1 to 6 levels were analyzed by Western blotting., Results: Western blotting and immunocytochemistry demonstrated high expression of α-SMA in lens epithelial cells treated with TGFβ2. The HDAC inhibitors exerted dose-dependent inhibition of α-SMA expression, with complete inhibition occurring with 0.5 μM of TSA and 2.5 μM of SAHA. Transforming growth factor β2-induced EMT was suppressed by TSA and SAHA. Histone deacetylase inhibition in pig lens epithelia led to increased acetylation of histone 3 and 4 at multiple sites., Conclusions: Histone deacetylase inhibitors, TSA, and SAHA prevent EMT in lens epithelial explants. The results also suggest that the epigenetic modifiers are the potential targets to control PCO after cataract surgery., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)