Effect of four different intraocular lenses on posterior capsule opacification

AIM: To evaluate the impact of 4 different intraocular lenses(IOLs) on posterior capsule opacification(PCO) by comparing the neodymium: yttrium-aluminum-garnet(Nd:YAG) laser capsulotomy rates.METHODS: This retrospective study included 4970 eyes of 4013 cataract patients who underwent phacoemulsification and IOL implantation between January 2000 and January 2008 by the same surgeon at one clinic. Four different IOLs were assessed. The outcome parameter was the incidence of Nd:YAG laser posterior capsulotomies.· RESULTS: An Nd:YAG laser posterior capsulotomy was performed in 153(3.07%) of the 4970 eyes. The mean follow-up time was 84 mo for all of the IOL groups. The percentage of eyes developing PCO was significantly greater for the acrylic hydrophilic IOLs than for the hydrophobic IOLs, although eyes with acrylic hydrophilic IOLs did not require Nd:YAG laser capsulotomy as soon as eyes with acrylic hydrophobic IOLs. There was no difference between the long-term PCO rates when 1-and 3-piece acrylic hydrophobic IOLs were compared or when IOLs made of the same material but with different haptic angles were compared.· CONCLUSION: In this study, eyes with acrylic hydrophilic IOLs were more likely to develop PCO than those with acrylic hydrophobic IOLs. The lens design(1-piece versus 3-piece and varying haptic angles) did not affect the PCO rate.

Comparison of posterior capsule opacification at 360-degree square edge hydrophilic and sharp edge hydrophobic acrylic intraocular lens in diabetic patients

·AIM: To compare posterior capsule opacification(PCO)degree and visual functions after phacoemulsification in eyes implanted with 360-degree square edge hydrophilic acrylic intraocular lens(IOL)(570C C-flex, Rayner) and sharp edge hydrophobic acrylic IOL(Sensar AR40 e,AMO) in diabetic patients.· METHODS: Sixty diabetic patients underwent uneventful phacoemulsification and randomly implanted one of the two IOLs. The PCO value was measured by retroillumination photographs and Evaluation of Posterior Capsule Opacification(EPCO) 2000 image-analysis software at 1, 6, 12, and 24 mo after surgery. Visual acuity, and contrast sensitivity in photopic and mesopic conditions were also examined at each follow up time point. The incidence of eye that required Nd:YAG laser posterior capsulotomy were also compared.·RESULTS: There was not any statistically significant difference in PCO scores between Rayner C-flex 570 C group and Sensar AR40 e group at each follow up time point. Visual acuity, Nd:YAG capsulotomy incidence and contrast sensitivity also had no significant difference during the 24 mo follow-up.·CONCLUSION: For diabetic patients, Rayner 570 C Cflex and Sensar AR40 e IOLs are same effective for prevent PCO. The 360-degree square edge design maybe is a good alternative technique to improve PCO prevention.

Anterior segment OCT application in quantifying posterior capsule opacification severity with varied intraocular lens designs

AIM:To evaluate the application of anterior segmentoptical coherence tomography(AS-OCT)in posterior capsule opacification(PCO)severity assessment and analyse the relationship between PCO severity and intraocular lens(IOL)characters.METHODS:PCO patients were prospectively recruited.Cross-sectional images of the anterior segment at horizontal and vertical meridians were acquired with AS-OCT.The area of the IOL-PC(posterior capsular)space and PCO severity(area,thickness,and density at 3 mm and 5 mm IOL optic regions)were measured.The relationship between PCO severity and visual acuity,comparisons of PCO severity and IOL-PC space using varied IOL designs were analysed.RESULTS:One hundred PCO eyes were enrolled.IOL-PC space,PCO thickness and area were positively correlated with axial length.In addition,PCO area and thickness were positively correlated with visual acuity when it was≤0.52 log MAR.The cut-off level of visual acuity should be 0.52 log MAR.With varied IOL designs,3-piece C haptic IOL showed a smaller PCO area and thickness than the 1-piece 3 haptic IOL and 1-piece 4 haptic IOL.PCO area and thickness values for an IOL with a diameter≤11.0 mm was greater than for an IOL with a diameter of 12.5 mm,and the differences were statistically significant.PCO area and thickness increased when IOL haptic angulation increased(from 0 to 12 degrees).CONCLUSION:In PCO eyes,cut-off level of visual acuity is 0.52 log MAR.With more severe PCO,visual acuity maybenot enough to describe the visual function impairment.PCO severity and IOL-PC space are significantly correlated with axial length and IOL design and material.

Experimental study on cyclosporine A drug delivery system in prevention of posterior capsule opacification after intraocular lens implantation in rabbits

Objective To study the effect of cyclosporine A drug delivery system (CsA-DDS) on the prevention of posterior capsule opacification (PCO) after experimental intraocular lens implantation in rabbit eyes. Methods Twenty healthy New Zealand white rabbits, whose left eyes and right eyes were used respectively as experiment eyes and controls, were subjected to extracapsular lens extraction and artificial lens implantation. During the operation, CsA-DDS with poly (lactideco-glycolide) as carriers or empty DDS was implanted in the capsular bag for the experimental eyes and controls respectively. After the operation, anterior chamber reaction, intraocular pressure (IOP) and CsA concentration were monitored and twelve weeks after the operation, the eyes were extracted for histopathological and morphological examinations. Results There were no differences between the two groups in conjunctival congestion, IOP change and anterior chamber reaction. PCO was less severe in the experimental eyes than in the controls. Light microscopy revealed that posterior capsular membrane in the experimental eyes was slick, with no obvious proliferation, whereas in the controls, there were lens epithelial cell proliferation and cortex regeneration of different degrees. Morphological examination with electron microscope showed that in the experimental eyes, lens epithelial cells did not function actively and apoptosis occurred, whereas in the controls, epithelial cells presented active function. No marked ultrastructural changes were found in either group. Conclusion Cs-DDS can inhibit PCO after intraocular lens implantation in rabbit eyes and does not have toxic effects on the surrounding ocular tissues. Therefore, it has a good potential for clinical use in prevention of PCO.

Prophylaxis of posterior capsule opacification through autophagy activation with indomethacin-eluting intraocular lens

Posterior capsule opacification(PCO)is the most common long-term postoperative complication of cataract surgery,leading to secondary vision loss.Optimized intraocular lens(IOL)structure and appropriate pharmacological intervention,which provides physical barriers and biological inhibition,respectively,can block the migration,proliferation,and epithelial-mesenchymal transition(EMT)of lens epithelial cells(LECs)for PCO prophylaxis.Herein,a novel indomethacin-eluting IOL(INDOM-IOL)with an optimized sharper edge and a sustained drug release behavior was developed for PCO prevention.Indomethacin(INDOM),an ophthalmic non-steroidal anti-inflammatory drug(NSAID)used for postoperative ocular inflammation,was demonstrated to not only be able to suppress cell migration and down-regulate the expression of cyclooxygenase-2(COX-2)and EMT markers,including alpha-smooth muscle actin(α-SMA)and cyclin D1,but also promote the autophagy activation in LECs.Additionally,autophagy was also verified to be a potential therapeutic target for the down-regulation of EMT in LECs.The novel IOL,serving as a drug delivery platform,could carry an adjustable dose of hydrophobic indomethacin with sustained drug release ability for more than 28 days.In the rabbit PCO model,the indomethacin-eluting IOL showed excellent anti-inflammatory and anti-PCO effects.In summary,indomethacin is an effective pharmacological intervention in PCO prophylaxis,and the novel IOL we developed prevented PCO in vivo under its sustained indomethacin release property,which provided a promising approach for PCO prophylaxis in clinical application.

An experimental study on the effects of curcumin on posterior capsule opacification in young rabbit eyes

Background Posterior capsule opacification （PCO） compromises vision development in infants after cataract surgery and lead to amblyopia. To observe the effects of curcumin on PCO in infant rabbits, curcumin was injected under the capaule and into the anterior chamber during phacoemulsification. Methods Seventy-five 1-month-old healthy New Zealand white rabbits were randomized into 3 groups, one eye of each rabbit was randomly selected to be operated. The operation involved continuous circular capsulorhexis, followed by hydrodissection with 0.6 ml each of balanced salt solution （BSS, group A）, hydroxypropyl-β-dodextrJn （HP-13-CD, 90μg/ml, group B） or CUR-HP-β-CD （123 μg/ml, group C）, respectively. After phacoemulsification, 0.4 ml of each drug solution was injected into the anterior chamber via an incision. The extent of corneal edema and the inflammatory response within the anterior chamber were considered as measures PCO and observed postoperatively. All eyes were examined 1 and 2 months postoperative by slit lamp microscopy and photography after pupil dilation. On the third day postoperative, 6 rabbits from each group were executed. Paraffin-embedded sections were stained with hematoxylin-eosin （HE） or terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL, indicative of apoptosis）. Stained sections were observed under light microscopy. Proliferation of lens epithelial cells （LECs） was observed microscopically on day 3, day 7, month 1 and month 2 after the operation with HE staining. Results The remission of cornea edema occurred earlier in group C than in groups A and B （P 〈0.05）; there were no significant differences between groups A and B. The remission of anterior chamber exudation in group C was earlier than those in groups A and B （P 〈0.05）. No significant difference in the times when PCO occurred, was observed among groups. Compared to groups A and B, the extent of PCO was less severe （P〈0.05）. Three days after the operation, LECs aggregated at the orbit. Meanwhile, minor apoptosis was observed in all groups. One month after the operation transparent, cortex and proliferating LECs were observed near the orbit in groups A and B. Two months postoperative, heavy cortex proliferation was observed in all groups： epithelial cells migrated and aggregated at the posterior capsule and rearranged under the anterior capsule in the control group. Proliferation was also observed in group C, but to a less severe extent than in the other two groups. Conclusion CUR-HP-β-CD exerts an inhibitory effect on PCO.

Induction of oxidative stress in human aqueous and vitreous humors by Nd:YAG laser posterior capsulotomy

AIM： To evaluate whether the Q-switched Nd：YAG laser treatment applied in routine capsulotomy elicits oxidative stress in aqueous and vitreous humors. METHODS： Thirty-six patients who had to undergo a 25 gauge pars plana vitrectomy due to vitreoretinal disorders were enrolled, 15 of them underwent a Q-switched Nd：YAG laser capsulotomy 7 d before vitrectomy due to posterior capsule opacification（PCO）（Nd：YAG laser group） while the remaining 21 patients were not laser treated before vitrectomy（no Nd：YAG laser group）. Samples of the aqueous and vitreous humors were collected during vitrectomy from all patients for the assessment of oxidative parameters which were compared between the Nd：YAG laser group and no Nd：YAG laser group. Thiobarbituric acid reactive substances（TBARS）, a product of membrane lipid peroxidation, nitrite levels, the antioxidative activities of SOD and catalase, the 4-HNE-protein conjugate formation, indicating structural modifications in proteins due to lipoperoxidation, were assessed in aqueous and vitreous samples. RESULTS： In the human vitreous humor TBARS levels are significantly higher in the Nd：YAG laser group compared to the no Nd：YAG laser group and importantly, there is a significant correlation between the TBARS levels and the total energy of Nd：YAG laser used during capsulotomy.Moreover the anti-oxidative activities of SOD and catalase were significantly decreased by Nd：YAG laser treatment, both in aqueous and vitreous humors. In accordance with the TBARS data and anti-oxidative enzyme activities, significantly higher levels of proteins were conjugated with the lipoperoxidation product 4-HNE in the aqueous and vitreous humors in the Nd：YAG laser-treated group in comparison to no Nd：YAG laser group. CONCLUSION： These data, clearly suggest that any change that Q-switched Nd：YAG photo disruption may cause in the aqueous and vitreous compartments, resulting in a higher level of oxidative damage might be of considerable clinical significance particularly by accelerating the aging of the anterior and posterior segments of the eye and by worsening the intraocular pressure, the uveal, the retinal（especially macular） pathologies.

miRNA-26b suppresses the TGF-β2-induced progression of HLE-B3 cells via the PI3K/Akt pathway

AIM:To study the effect of mi R-26 b on lens epithelial cells induced by transforming growth factor beta(TGF-β)2 and the underlying signaling pathways.METHODS:Human lens epithelial cell line B-3(HLE-B3)was incubated with TGF-β2(5 ng/m L)and then transfected with mi R-26 b mimics.The expression of mi R-26 b was determined using quantitative reverse transcriptase polymerase chain reaction(q RT-PCR),while 5’-bromodeoxyuridine(Brd U)and wound-healing assays were used to measure the growth and migration of HLE-B3 cells,respectively.The expression of epithelialmesenchymal transition(EMT)markers and the activity of the phosphatidylinositol 3-kinase(PI3 K)/Akt pathway were measured by Western blotting assay and immunofluorescence staining.Electron microscopy was also used to observe cellular morphology.RESULTS:The expression levels of mi R-26 b were significantly reduced in human posterior capsular opacification-attached lens tissue and TGF-β2-stimulated HLE-B3 cells.In the presence of TGF-β2,the growth,migration,and EMT of HLE-B3 cells were distinctly enhanced;these effects were attenuated by the administration of mi R-26 b mimics.Furthermore,the overexpression of mi R-26 b significantly reduced upregulation of the PI3 K/Akt pathway when stimulated by TGF-β2 in HLE-B3 cells.Moreover,the addition of an activator(740 Y-P)led to the upregulation of the PI3 K/Akt pathway and abolished the protective effect of mi R-26 b on the HLE-B3 cells that was mediated by TGF-β2.CONCLUSION:The mi R-26 b suppresses TGF-β2-induced growth,migration,and EMT in HLE-B3 cells by regulating the PI3 K/Akt signaling pathway.

TGF-β2-induced NEAT1 regulates lens epithelial cell proliferation,migration and EMT by the miR-26a-5p/FANCE axis

AIM:To explore the regulatory mechanism of nuclear paraspeckle assembly transcript 1(NEAT1)in the pathogenesis of posterior capsule opacification(PCO).METHODS:Quantitative reverse transcription polymerase chain reaction(RT-q PCR)was executed to analyze NEAT1 and micro RNA(miR)-26a-5p expression in transforming growth factor-beta 2(TGF-β2)-disposed lens epithelial cells(LECs).The proliferation,cell cycle progression,apoptosis,and migration of TGF-β2-disposed LECs were evaluated.The relationship between NEAT1 or fanconi anemia(FA)complementation group E(FANCE)and miR-26a-5p was verified by dual-luciferase reporter assay.RESULTS:TGF-β2 induced NEAT1 expression in LECs.NEAT1 inhibition accelerated apoptosis,cell cycle arrest,decreased proliferation,epithelial-mesenchymal transition(EMT),and migration of TGF-β2-disposed LECs.NEAT1 sponged miR-26a-5p to further regulate FANCE expression.Rescue experiments presented that miR-26a-5p downregulation overturned NEAT1 silencing-mediated impacts on TGF-β2-disposed LEC biological behaviors.Additionally,FANCE overexpression reversed miR-26a-5p mimic-mediated impacts on TGF-β2-disposed LEC biological behaviors.CONCLUSION:TGF-β2-induced NEAT1 facilitates LEC proliferation,migration,and EMT by upregulating FANCE via sequestering miR-26a-5p.

Apoptosis of lens epithelial cells induced by cinobufagin in vitro

AIMTo investigate the in vitro effects and mechanism of action of cinobufacini on apoptosis of lens epithelial cells (LEC).

Cumulative probability and risk analysis for Nd:YAG laser capsulotomy

AIM: To estimate the cumulative probability of Nd:YAG capsulotomy at a teaching institution and evaluate secondary risk factors.METHODS: The records of all patients who underwent phacoemulsification with intraocular lens(IOL) placement between 2005-2010 were retrospectively reviewed. The cumulative probability of Nd:YAG capsulotomy(capsulotomy) was calculated using KaplanMeier survival analysis and secondary risk factors were evaluated using the Cox proportional hazards regression model. RESULTS: One thousand three hundred and fifty four charts were reviewed. A total of 70 capsulotomies wereperformed. The mean follow-up was 19.4 mo(standard deviation 17 mo). The cumulative probability of capsulotomy was 4% at 1 year, 5% at 2 year, and 9% at 3 year. Multivariate analysis demonstrated an increased risk with younger age(HR = 1.03, CI 1.01-1.05, P = 0.007), placement of sulcus IOL(HR = 2.57, CI 1.32-4.99, P = 0.005), ocular trauma(HR = 2.34, CI 1.13-4.83, P = 0.02), and phacoemulsification by a more experienced surgeon(HR = 4.32, CI 1.89-9.87, P = 0.001).CONCLUSION: Cumulative probability of capsulotomy was lower than previously reported. Posterior capsule opacification was strongly associated with younger age and factors associated with high-risk cataract surgery. Surgeon awareness to the risk factors that correlate with posterior capsulotomy may allow for more thorough pre-operative disclosure and enhance patient satisfaction.

AB083.Intraocular lens biocompatibility:a novel,objective approach

Background:Understanding factors that contribute to posterior capsular opacification(PCO)development is a significant public concern as treatment can lead to complications.In order to prevent PCO,a better understanding of intraocular lens(IOL)characteristics,including design and material,and patient interaction is required.Herein,we performed a retrospective multivariable analysis to determine which factors(IOL and patient based)were least likely to result in PCO.Methods:One hundred eighty post-mortem eyes with implanted IOLs were collected from the Minnesota Eye Bank,along with clinical history,including date of cataract surgery and IOL model number.The capsular bag(CB)with the IOL implant was removed from all eyes to obtain digital images.PCO outcome was quantified on CB images using an objective,automated custom image analyzer(Medical Parachute Automated Detector Opacification Software).The software measured intensity and area of the opacification within the IOL optic edge,intra-optic edge(IOE=intensity/area),and in Soemmering’s ring(SR=intensity/area).Epidemiologic analysis assessed which IOL characteristics and patient-related factors correlated with PCO.IOL factors included material,edge design,lens filter,company,IOL model,decentration and time from cataract surgery to death.Patient factors included sex,age and diabetes,among others.Results:Multivariate analyses showed non-diabetic patients had less PCO(P=0.05).Individuals 50-80 years old compared to 80+had lower SR PCO(P=0.04).Non-blue light filter IOLs had lower SR and IOE PCO compared to filter IOLs(P=0.03,0.001).Square and frosted optic edge design had lower SR and IOE PCO rates compared to OptiEdge and round optic edge design(P=0.002,0.02).The IOL model that had the least PCO was the ZA9003 model,but this was only significant for SR and not IOE PCO(P=0.04).Adjusting for patient-factors,IOL lens model was no longer a confounding factor for PCO.Patients with an IOL implanted for<7 years had lower SR PCO,whereas lower IOE PCO was only seen in implants<4 years old(P=0.0001,0.04).Conclusions:In order to generate a lens that does not develop PCO,it is critical to understand the IOL-and patient-related factors that lead to PCO development.Based on our data,the most susceptible patients are elderly and diabetic,and it may be preferable to implant a square and frosted edge lens without blue-light filtering in this cohort.

TGF-β regulation of microRNA miR-497-5p and ocular lens epithelial cell mesenchymal transition

The purpose of this study was to investigate the role of a human lens microRNA(miR-497-5p) in regulating epithelialmesenchymal transition(EMT) under the control of transforming growth factor beta(TGF-β). A microRNA array was used to evaluate the microRNA profiles of untreated and TGF-β-treated human lens epithelial cells in culture. This showed that TGF-βtreatment led to the upregulation of 96 microRNAs and downregulation of 39 microRNAs. Thirteen microRNAs were predicted to be involved in the pathogenesis of posterior capsule opacification(PCO). Meanwhile, overexpression of miR-497-5p suppressed cell proliferation and EMT 48 h post-transfection, and inhibition of miR-497-5p accelerated cell proliferation and EMT.Treatment with TGF-β inhibited the expression of miR-497-5p, but not cell proliferation. miR-497-5p was also found to regulate the level of CCNE1 and FGF7, which are reported to be actively involved in EMT. CCNE1 and FGF7 were bona fide targets of miR-497-5p. The results suggest that miR-497-5p participates in the direct regulation of lens epithelial cell EMTand is regulated by TGF-β. miR-497-5p may be a novel target for PCO therapy.