Aldose reductase inhibition enhances lens regeneration in mice.

After cataract surgery, epithelial cells lining the anterior lens capsule can transition to one of two divergent pathways, including fibrosis which leads to posterior capsular opacification (PCO), or lens fiber cell differentiation which leads to regeneration of lens material. We previously showed that the PCO response can be suppressed with aldose reductase (AR) inhibitors. In this present study we show that AR inhibition, both genetic and pharmacologic with Sorbinil, can augment the process of lens regeneration. Extracapsular lens extraction (ECLE) was carried out in C57BL/6 (WT), AR overexpression (AR-Tg), and AR knockout (ARKO) mice, and in some cases in mice treated with the AR inhibitor sorbinil. Whole eyes were harvested approximately 8 weeks after ECLE and evaluated by histological analysis and immunostaining for the fiber cell marker γ-crystallin. All eyes examined for lens regeneration were paraffin embedded for serial sectioning to produce three-dimensional reconstructed models of lens morphology and size. We observed that AR-null mice respond to ECLE by regenerating a lens-like structure with a circular shape and array of cell nuclei reminiscent of the lens bow region typical of the native mammalian lens. Although WT and AR-Tg eyes also produced some regenerated lens material after ECLE, their structures were consistently smaller than ARKO regenerated lenses. WT mice treated with sorbinil showed higher levels of lens regeneration after ECLE compared to WT mice, as assessed by size and three-dimensional morphology. Altogether, this study adds evidence for a critical role for AR in the response of lens epithelial cells to cataract extraction and lens regeneration.

Aldose Reductase Inhibition Prevents Development of Posterior Capsular Opacification in an In Vivo Model of Cataract Surgery.

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.

Neovascular Age-Related Macular Degeneration Disease Quiescence with Visual Acuity Stability in a Subgroup of Patients Following PRN Treatment.

PURPOSE: This study evaluates long-term visual acuity (VA) outcomes in patients with prolonged clinically quiescent neovascular age-related macular degeneration (AMD) after treatment with a pro re nata (PRN) regimen of anti-vascular endothelial growth factor agents (bevacizumab, ranibizumab, and/or aflibercept). METHODS: This retrospective study analyzes VA changes in 105 eyes from 72 patients with a period of AMD disease quiescence (determined by retinal examination) not requiring treatment for at least 180 days. All patients were seen at Colorado Retina Associates between October 31, 2005 and December 31, 2015. VA was measured at the time of first treatment, last treatment, and final clinic visit showing changes in VA during the treatment and quiescent periods. The sample was stratified to compare those with VA gain throughout the study to those with VA loss. RESULTS: The aggregate group showed VA stability during the treatment period (20/117 to 20/116) with a significant decline during the quiescent period (to 20/235; P < 0.001). The VA gainers had a significant increase in VA during the treatment period (20/187 to 20/88; P < 0.001) and VA stability during the quiescent period (to 20/93). VA losers had a significant decline in VA during both the treatment and quiescent periods (P < 0.001). CONCLUSION: Overall, PRN treatment resulted in a decline in VA during a period of apparent disease quiescence. There is a group of patients that does not lose VA during this period, and if patients like these can be identified, their treatment could be optimized to include a period of clinically justified nontreatment.

Endoscopic Management of Paranasal Sinus Mucoceles: Meta-analysis of Visual Outcomes.

Objective Paranasal sinus mucoceles are benign cystic lesions originating from sinus mucosa that can impinge on adjacent orbital structures, causing ophthalmic sequelae such as decreased visual acuity. Definitive treatment requires surgery. We present the first meta-analysis quantifying the effect of preoperative visual function and time to surgery on postoperative visual acuity outcomes. Data Sources PubMed, Ovid, Embase, Web of Science, and the Cochrane Library. Methods Two independent authors systematically reviewed articles describing outcomes after endoscopic sinus surgery for paranasal sinus mucoceles presenting with visual loss. Available data from case reports and series were combined to analyze the associations among preoperative visual acuity, time to surgery, and postoperative outcomes. Results Eighty-five studies were included that provided data on 207 patients. The average presenting visual acuity was 1.57 logMAR (logarithm of the minimum angle of resolution), and the average postoperative visual acuity was 0.21 logMAR, with visual improvement in 71.5% of cases. Preoperative visual acuity ≥1.52 logMAR correlated with postoperative improvement >1 logMAR ( R = 0.4887, P < .0001). A correlation was found between a time to surgery <6 days and postoperative improvement ( R = 0.297, P < .0001). Receiver operator curve analysis of these thresholds demonstrated a moderately accurate prognostic ability (area under the curve: 75.1 for preoperative visual acuity and 73.1 for time to surgery). Conclusion Visual loss resulting from paranasal sinus mucoceles is potentially reversible in most cases, even those presenting with poor vision. When possible, surgery should be performed promptly after diagnosis, but emergency surgery does not appear to be necessary for vision restoration.

The safety and efficacy of Diphoterine for ocular and cutaneous burns in humans.

CONTEXT: Diphoterine, developed by the French company Prevor, is a polyvalent, chelating, amphoteric and slightly hypertonic solution used in the management of chemical cutaneous and ocular burns. While used extensively in Europe and Canada, it is has not been approved by the United States Occupational Safety and Health Administration (OSHA) as an alternative to the water-rinse method due to a lack of evidence of its safety and efficacy on human subjects. An unbiased and extensive systematic review was undertaken in order to better understand Diphoterine's safety and efficaciousness on humans. OBJECTIVE: Review the safety and efficacy of Diphoterine for treating chemical burns of the skin and eyes in humans. METHODS: Data sources: Information sources included Pubmed, the National Library of Medicine's Medline Database and the "Publications" sections of the Prevor website. Search terms included Diphoterine, chemical burn, ocular burn and cutaneous burn. STUDY SELECTION: Any study type published through a peer-reviewed journal up to May 2016 was considered eligible. Published data must have included Diphoterine in the treatment of chemical burns on the skin or eyes as well as meet other specified criteria. Acceptable studies had to use either a quantitative (e.g. number of work days lost) or qualitative (e.g. level of erythema) approach when measuring cutaneous or ocular lesion outcomes. DATA EXTRACTION: Independent assessment of article inclusion by two authors using predefined criteria. RESULTS AND CONCLUSION: Diphoterine is safe and highly effective in improving healing time, healing sequelae and pain management of chemical burns on the skin and eyes of humans. Outcomes are significantly improved when compared to water or a physiologic solution equivalent. We recommend that this product be readily available to emergency responders and companies that expose their employees to hazardous chemical substances in order to improve healing sequelae, pain management and lost work days from these types of burns.