The Protective Effect of Metformin Use on Early Nd:YAG Laser Capsulotomy.

Purpose: To determine the effect of metformin on early Nd:YAG laser treatment for posterior capsule opacification (PCO) and to explore a molecular mechanism to explain a possible protective effect of metformin against PCO. Methods: We conducted: 1) a retrospective cohort study of patient eyes undergoing phacoemulsification at our institution; and 2) laboratory investigation of the effect of metformin on the behavior of lens epithelial cells in the context of an animal model for PCO. Population-averaged Cox proportional hazards modeling was used to estimate risk for time to Nd:YAG. For laboratory studies, expression of markers for epithelial-to-mesenchymal transition (EMT) implicated in PCO pathogenesis was measured in tissue culture and following extracapsular lens extraction in a mouse model. Results: The rate of Nd:YAG laser capsulotomy was 13.1% among the 9798 eyes. Both metformin use and diabetes were protective factors for Nd:YAG laser capsulotomy in univariate analysis. However, in multivariable analysis with nondiabetics as the reference group, only metformin use among diabetics was significantly protective of Nd:YAG (hazard ratio: 0.68, 95% CI: 0.54-0.85, P = 0.0008), while eyes of patients with diabetes without metformin use did not significantly differ (P = 0.5026). Treatment of lens epithelial cells with metformin reduced the level of the EMT markers ⍺-SMA and pERK induced by TGF-ß2. Similarly, metformin treatment reduced ⍺-SMA expression in lens epithelial cells following extracapsular lens extraction in a mouse model. Conclusions: The protective effect of metformin against early Nd:YAG may relate to its ability to downregulate EMT in residual lens epithelial cells that otherwise trend toward myofibroblast development and PCO.

CuInS/ZnS quantum dots modified intraocular lens for photothermal therapy of posterior capsule opacification.

Posterior capsule opacification (PCO) after cataract surgery is one of the leading causes of visual impairment and blindness. The cause of PCO is the capsule fibrosis developed on implanted Intraocular Lens (IOLs) by the de-differentiation of Lens Epithelial Cells (LECs) undergoing epithelial mesenchymal transition. How to prevent PCO has been a challenge to scientists and ophthalmologists for decades. Here we demonstrated the use of carboxylated CuInS/ZnS quantum dots (ZCIS QDs), which are free of toxic heavy metals and are more biocompatible, as photothermal nanomedicines. The ZCIS QDs are modified onto the non-optical section of IOLs by a facial activation-immersion method. Under mild NIR laser irradiation, ZCIS QDs modified IOLs (QDs-IOLs) will generate localized heat and prevent the proliferation of LECs onto the surface of QDs-IOLs. Our findings provide experimental evidence for further application of combined nanotechnology and photothermal therapy for the clinical treatment of PCO.

Poly(lactic-co-glycolic) Acid as a Slow-Release Drug-Carrying Matrix for Methotrexate Coated onto Intraocular Lenses to Conquer Posterior Capsule Opacification.

PURPOSE: Posterior capsule opacification (PCO) still represents the main long-term complication of cataract surgery. Research into pharmacologic PCO prophylaxis is extensive. One promising candidate drug is methotrexate (MTX). Our aim is to determine the in vitro feasibility of MTX-loaded poly(lactic-co-glycolic) (PLGA) biomatrices sprayed on intraocular lenses (IOLs) as a drug-delivery implant. METHODS: Hydrophilic and hydrophobic acrylic IOLs were spray-coated with MTX-loaded PLGA. Unsprayed, solvent only, and solvent-PLGA-sprayed IOLs served as controls. All IOLs were evaluated for their growth-inhibiting properties in an in vitro anterior segment model and the ex vivo human capsular bag. The release kinetics of MTX from the IOLs was determined. The toxicity of MTX on corneal endothelial cells was evaluated by using a dye reduction colorimetric assay. MTX was also used in a scratch assay. RESULTS: MTX-PLGA-IOL showed a significant difference in cell proliferation and migration compared with all controls in the anterior segment model (p < 0.001) and in the human capsular bag model (p = 0.04). No difference in viability was observed on corneal endothelial cells (p = 0.43; p = 0.61). MTX significantly inhibited cells in the scratch assay (p = 0.02). At all measured points, the released MTX dose remained above EC50 and below the toxic dose for the endothelium. CONCLUSIONS: In view of the strong inhibition of PCO in vitro with the lack of toxic effects on a corneal cell line, MTX encapsulating microspheres seem to be a promising method for modifying IOL.

Microplasma Induced Cell Morphological Changes and Apoptosis of Ex Vivo Cultured Human Anterior Lens Epithelial Cells - Relevance to Capsular Opacification.

Inducing selective or targeted cell apoptosis without affecting large number of neighbouring cells remains a challenge. A plausible method for treatment of posterior capsular opacification (PCO) due to remaining lens epithelial cells (LECs) by reactive chemistry induced by localized single electrode microplasma discharge at top of a needle-like glass electrode with spot size ~3 µm is hereby presented. The focused and highly-localized atmospheric pressure microplasma jet with electrode discharge could induce a dose-dependent apoptosis in selected and targeted individual LECs, which could be confirmed by real-time monitoring of the morphological and structural changes at cellular level. Direct cell treatment with microplasma inside the medium appeared more effective in inducing apoptosis (caspase 8 positivity and DNA fragmentation) at a highly targeted cell level compared to treatment on top of the medium (indirect treatment). Our results show that single cell specific micropipette plasma can be used to selectively induce demise in LECs which remain in the capsular bag after cataract surgery and thus prevent their migration (CXCR4 positivity) to the posterior lens capsule and PCO formation.

The assessment of changes in macular thickness in diabetic and non-diabetic patients: the effect of topical ketorolac on macular thickness change after ND:YAG laser capsulotomy.

PURPOSE: The purpose of our study is to assess the changes in macular thickness (MT) in diabetic and non-diabetic patients and to research effects of topical ketorolac (Acular®, Allergan, Irvine, CA) on MT change after neodymium:yttrium aluminum garnet (Nd:YAG) laser capsulotomy. MATERIAL AND METHODS: This study involved 88 eyes of 88 patients diagnosed as posterior capsule opacification (PCO). Patients were divided into four groups according to presence of diabetes mellitus (DM) and drugs used after capsulotomy. Group 1: Patients with DM using only 0.1% Fluorometholon (FML®, Allergan, Irvine, CA) after capsulotomy (22 patients). Group 2: Patients with DM using 0.5% ketorolac (Acular®) and 0.1 Fluorometholon (FML®, Allergan, Irvine, CA) after capsulotomy (20 patients). Group 3: Patients without DM using only 0.1% Fluorometholon (FML®, Allergan, Irvine, CA) (22 patients). Group 4: Patients without DM using 0.5% ketorolac (Acular®) and 0.1% Fluorometholon (FML®, Allergan, Irvine, CA) (24 patients). A plus-shaped capsulotomy was performed using VISULAS® YAGIII (Carl Zeiss) laser microscope. MT measurement with Cirrus SD-OCT (Carl Zeiss Opthalmic System Inc., Model 400, Dublin, CA, Software 5) were done. Measurements were done before laser, and on the first day, first week, first month, third month and sixth month after laser capsulotomy. We compared the four groups for MT change during 6 months. RESULTS: Group 1 involving patients with DM using only 0.1% Fluorometholon (FML®, Allergan, Irvine, CA) after capsulotomy had increased MT at the first week, and the first, third, and sixth month after laser (p < 0.001). Group 3 involving patients without DM using only 0.1% Fluorometholon (FML®, Allergan, Irvine, CA) had increased MT at the first week, and at the first and third month, there was no statistically significant difference at the sixth month (p > 0.05). There was no statistically significant increase in MT during the follow-up period in group 2 involving patients with DM using 0.5% ketorolac (Acular®) and 0.1 Fluorometholon (FML®, Allergan, Irvine, CA) after capsulotomy and group 4 involving patients without DM using 0.5% ketorolac (Acular®) and 0.1% Fluorometholon (FML®, Allergan, Irvine, CA) (p > 0.05). CONCLUSION: An increase in MT can be observed after Nd:YAG laser capsulotomy, especially in diabetic patients. Adding topical ketorolac (Acular®, Allergan, Irvine, CA) to topical Fluorometholon (FML®, Allergan, Irvine, CA) therapy after YAG laser capsulotomy can prevent this increase.

[Posterior capsule opacification]. / La cataracte secondaire.

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.

[Prevention of posterior capsule opacification in experimental studies]. / Profilaktyka zmetnienia torebki tylnej soczewki w badaniach doswiadczalnych.

The pharmaceuticals inhibiting proliferation of epithelium cells or causing their death were tested in experimental studies on PCO prevention. The following antymetabolites were tested: 5-fluorouracil, dounomycin, methotrexat and colchicine, epithelial antibodies against epithelial cells, toxins, hyperosmolar agents and heparin, indomethacine and lignocaine. Moreover, gene therapy with the use of apoptose genes was applied. None of the attempts to prevent PCO was useful for effective and safe clinical treatment.

Impact of anterior capsule polishing on anterior capsule opacification after cataract surgery: a randomized clinical trial.

AIMS: To evaluate the effect of anterior capsule polishing on the development of anterior capsule opacification (ACO) in patients undergoing cataract surgery. METHODS: This prospective randomized observational double-masked clinical trial comprised 120 eyes of 60 consecutive patients with bilateral age-related cataract who underwent phacoemulsification. The patients were randomly assigned to one of the two groups: One eye received a 360 degree anterior capsule polishing (group 1 (cases)) and the fellow eye was without anterior capsule polishing (group 2 (controls)) The primary observation was to observe the development of ACO between the 2 groups, whereas the secondary observation was to measure uveal inflammation. ACO was evaluated at 1 week, 1 month, and 6 months. RESULTS: At the 1-week follow-up, there was no significant difference in the development of ACO between the two groups. At 1 month, 54 (90%) eyes developed ACO in controls and 26 (43.3%) eyes in cases (P<0.001). However, at 6 months, there was no significant difference in the development of ACO between controls and cases (P=0.500). The odds of having cells and flare were significantly more in cases compared with controls at first postoperative day (cells: OR, 39.27; 95% CI, 13.49-114.26 and flare: OR, 48.0; 95% CI, 15.57-147.97). CONCLUSIONS: ACO was significantly lower at 1 month in cases compared with controls. However, the difference in ACO between the two groups was insignificant at 6 months. A significant difference in anterior segment inflammation was documented in cases on the first postoperative day. There was no detectable benefit of performing scraping on the anterior capsule to avoid opacification after phacoemulsification.E