Corneal re-innervation following refractive surgery treatments

Laser refractive surgery is one of the most performed surgical procedures in the world. Although regarded safe and efficient, it has side effects. All of the laser based refractive surgical procedures invoke corneal nerve injury to some degree. The impact of this denervation can range from mild discomfort to neurotrophic corneas. Currently, three techniques are widely used for laser vision correction: small incision lenticule extraction, laser-assisted keratomileusis in situ and photorefractive keratotomy. Each of these techniques affects corneal innervation differently and has a different pattern of nerve regeneration. The purpose of this review is to summarize the different underlying mechanisms for corneal nerve injury and compare the different patterns of corneal reinnervation

The effects of rho-associated kinase inhibitor Y-27632 on primary human corneal endothelial cells propagated using a dual media approach

10.1038/srep09167Scientific Reports

Enhancement after small-incision lenticule extraction

Purpose:To report the incidence, risk factors, and outcomes of enhancement after small-incision lenticule extraction (SMILE). Design:Retrospective cohort study.Participants:Five hundred twenty-four eyes of 307 patients who underwent SMILE at Singapore National Eye Center between February 2012 and March 2016. Methods:The data collected included patient age at primary SMILE, gender, race, preoperative and postoperative manifest refraction spherical equivalent (MRSE), preoperative and postoperative uncorrected distance visual acuity and corrected distance visual acuity, the occurrence of suction loss during the procedure, and the need for enhancement. All enhancements were carried out by performing an alcohol-assisted photorefractive keratectomy (PRK) procedure with application of mitomycin C (MMC).Main Outcome Measures:Incidence, prevalence, preoperative and intraoperative risk factors for enhancement, and outcomes after enhancement. Results:The prevalence of enhancement was 2.7%, and 71.4% eyes had enhancement within 1 year of primary SMILE. The incidence of enhancement was 2.1% and 2.9% at 1 and 2 years, respectively. Age older than 35 years, preoperative MRSE more than −6.00 diopters (D), preoperative myopia more than 6.00 D, preoperative astigmatism more than 3.00 D, and intraoperative suction loss were significant risk factors for enhancement after SMILE after adjusting for all other covariates (odds ratios, 5.58, 4.80, 1.41, 3.06, and 2.14, respectively; P = 0.004, 0.021, 0.022, 0.002, and 0.020, respectively). In the patients who underwent bilateral SMILE, the first-operated eye had a marginal trend toward significance for enhancement (P = 0.054). There was no gender or racial difference. In the 14 eyes requiring enhancement, the uncorrected distance visual acuity before enhancement ranged from 20/80 to 20/25, and the mean attempted enhancement spherical equivalent was −0.50±0.86 D. The uncorrected distance visual acuity improved in most patients (92.9%) after enhancement. Conclusions:The 2-year incidence of enhancement after SMILE was 2.9%. Risk factors associated with enhancement included older age at SMILE procedure, greater preoperative MRSE, greater preoperative myopia, greater preoperative astigmatism, and the occurrence of intraoperative suction loss. Clinical outcomes of using PRK with application of MMC for enhancement were good

Generation of novel monoclonal antibodies for the enrichment and characterization of human corneal endothelial cells (hCENC) necessary for the treatment of corneal endothelial blindness

Corneal transplantation is the primary treatment option to restore vision for patients with corneal endothelial blindness. Although the success rate of treatment is high, limited availability of transplant grade corneas is a major obstacle. Tissue-engineered corneal endothelial grafts constructed using cultivated human corneal endothelial cells (hCENC) isolated from cadaveric corneas may serve as a potential graft source. Currently, tools for the characterization of cultured hCENC and enrichment of hCENC from potential contaminating cells such as stromal fibroblasts are lacking. In this study, we describe the generation and characterization of novel cell surface monoclonal antibodies (mAbs) specific for hCENC. These mAbs could be used for enrichment and characterization of hCENC. Out of a total of 389 hybridomas, TAG-1A3 and TAG-2A12 were found to be specific to the corneal endothelial monolayer by immunostaining of frozen tissue sections. Both mAbs were able to clearly identify hCENC with good ‘cobblestone-like’ morphology from multiple donors. The antigen targets for TAG-1A3 and TAG-2A12 were found to be CD166/ALCAM and Peroxiredoxin-6 (Prdx-6), respectively, both of which have not been previously described as markers of hCENC. Additionally, unlike other Prdx-6 mAbs, TAG-2A12 was found to specifically bind cell surface Prdx-6, which was only expressed on hCENC and not on other cell types screened such as human corneal stromal fibroblasts (hCSF) and human pluripotent stem cells (hPSC). From our studies, we conclude that TAG-1A3 and TAG-2A12 are promising tools to quantitatively assess hCENC quality. It is also noteworthy that the binding specificity of TAG-2A12 could be used for the enrichment of hCENC from cell mixtures of hCSF and hPSC.ASTAR (Agency for Sci., Tech. and Research, S’pore

Intraobserver repeatability and interobserver reproducibility of corneal measurements in normal eyes using an optical coherence tomography-Placido disk device

10.1016/j.jcrs.2014.05.044Journal of Cataract and Refractive Surgery412372-38

Corneal inlays for presbyopia explanted due to corneal haze

PURPOSE: To present 3 patients who required explantation of KAMRA inlays (AcuFocus, Inc., Irvine, CA) due to visual symptoms caused by postoperative corneal haze. METHODS: Case series. RESULTS: All patients had good near and distance vision immediately following implantation. They developed visual symptoms 3 to 6 years later. All patients reported a decline in distance vision. Two patients had hyperopic shift with flattening of the central cornea. Six months following explantation, all patients reported improvement in visual symptoms. A reversal of hyperopic shift was also observed, with improvement in corneal profiles on topography. Histopathology of the explanted inlays showed thin, acellular collagenous fibrotic membranes over the inlays with occasional chronic inflammatory cells. CONCLUSIONS: It is important for health care professionals to be made aware of this reversible complication following KAMRA inlay implantation. Long-term monitoring is recommended

Femtosecond laser-assisted preparation of conjunctival autograft for pterygium surgery

Femtosecond laser-assisted conjunctival autografts (CAG) preparation was recently proposed. This study reports the outcomes of the first clinical trial on the use of laser to prepare CAG in pterygium surgery, and to compare the outcomes with those of manual technique. Forty eyes undergoing primary pterygium excision with laser-assisted CAG transplantation were prospectively included (L group). Two historical matched cohorts whose CAGs were prepared manually were compared (n = 78 eyes by the same experienced surgeon, M group; n = 78 eyes by trainees; TM group). We found the laser-created CAGs had only 11 μm deviation from the targeted thickness. The best-corrected visual acuity improved, and the astigmatism significantly decreased after surgery, with comparable efficacy across 3 groups. The 1-year recurrence rate was 2.5%, 3.8% and 7.7% in the L, M and TM groups, respectively (P = 0.12). There was no significant difference between the L and M groups in the complication rate (5.0% and 1.3%, respectively), surgical time (19.4 ± 5.1 and 19.1 ± 6.2 minutes, respectively), and postoperative discomfort scores (0.1 ± 0.3 and 0.2 ± 0.3, respectively), but these outcomes were significantly less favorable in the TM group. The results of this first comparative clinical trial suggest that femtosecond laser-assisted CAG preparation can be considered as an alternative technique for CAGs preparation.Published versio

Peroxiredoxin-1 regulates lipid peroxidation in corneal endothelial cells

Corneal transparency is maintained by a monolayer of corneal endothelial cells. Defects in corneal endothelial cells (CEnCs) can be rectified surgically through transplantation. Fuchs' endothelial corneal dystrophy (FECD) is the foremost cause of endothelial dysfunction and the leading indication for transplantation. Increased sensitivity of CEnCs to oxidative stress is thought to contribute to the pathogenesis of FECD through increased apoptosis. In part, this is thought to be due to loss of NRF2 expression: a global regulator of oxidative stress. We demonstrate that expression of the redox sensor, peroxiredoxin 1 (PRDX1) is selectively lost from CEnCs in FECD patient samples. We reveal that expression of PRDX1 is necessary to control the response of CEnCs to agents that cause lipid peroxidation. Iron-dependent lipid peroxidation drives non-apoptotic cell death termed ferroptosis. We establish that the inhibitor of ferroptosis, ferrostatin-1 rescues lipid peroxidation and cell death in CEnCs. Furthermore, we provide evidence that the transcription factor NRF2 similarly regulates lipid peroxidation in CEnCs.National Medical Research Council (NMRC)Published versionThis work was supported by the Singapore National Medical Research Council (NMRC), Clinician Scientist Award (NMRC/CSA-INV/0004/2015). The funding body had no role in study design, nor theanalysis and interpretation of data or the decision to publish

Early corneal wound healing and inflammatory responses after SMILE : comparison of the effects of different refractive corrections and surgical experiences

To investigate the early corneal wound healing and inflammatory responses after small incision lenticule extraction (SMILE) with different power of corrections and surgical experiences using a rabbit model.Twenty-four rabbits underwent SMILE with -2.00, -4.00, and -8.00 diopters (D) correction. One eye of each rabbit was operated on by surgeon 1 (experienced) and the contralateral eye was operated on by surgeon 2 (novice). Slit-lamp examination, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy were performed at 1 day and 1 week postoperatively. The corneas were harvested for immunofluorescence of markers for inflammation (CD11b), wound healing (fibronectin), and keratocyte response (HSP47).All corneas appeared clear throughout the follow-up period. In vivo confocal microscopy showed a greater reflectivity after -8.00 D than -2.00 D correction at day 1 at the lenticule anterior, posterior, and extracted lenticule planes (surgeon 1: P = .004, .041, and .038; surgeon 2: P = .012, .045, and .031). Different refractive corrections did not significantly affect the expression of CD11b, fibronectin, and HSP47. In the -2.00 D group, eyes operated on by surgeon 2 had thicker central corneal thickness evaluated by AS-OCT (P = .049) and exhibited more CD11b- and HSP47-positive cells at day 1 at the small vertical incision (P = .039 and .042).The early inflammatory and wound healing responses after SMILE were minimal. In the early postoperative period, less surgical experience resulted in an increased inflammatory response in low myopic corrections. Greater keratocyte response was seen in high myopic corrections irrespective of surgeon experience.NRF (Natl Research Foundation, S’pore

Nanotechnology for the treatment of allergic conjunctival diseases

Allergic conjunctivitis is one of the most common external eye diseases and the prevalence has been increasing. The mainstay of treatment is topical eye drops. However, low bioavailability, low ocular drug penetration, transient resident time on the ocular surface due to tear turnover, frequent topical applications and dependence on patient compliance, are the main drawbacks associated with topical administration. Nanotechnology-based medicine has emerged to circumvent these limitations, by encapsulating the drugs and preventing them from degradation and therefore providing sustained and controlled release. Using a nanotechnology-based approach to load the drug is particularly useful for the delivery of hydrophobic drugs such as immunomodulatory agents, which are commonly used in allergic conjunctival diseases. In this review, different nanotechnology-based drug delivery systems, including nanoemulsions, liposomes, nanomicelles, nanosuspension, polymeric and lipid nanoparticles, and their potential ophthalmic applications, as well as advantages and disadvantages, are discussed. We also summarize the results of present studies on the loading of immunomodulators or nonsteroidal anti-inflammatory drugs to nano-scaled drug delivery systems. For future potential clinical use, research should focus on the optimization of drug delivery designs that provide adequate and effective doses with safe and satisfactory pharmacokinetic and pharmaco-toxic profiles.Published versio