Clinical and material degradations of intraocular lenses: A review

Purpose: To review the published scientific literature concerning clinical and material degradations of intraocular lenses after implantation in cataract surgery. Methods: A search was undertaken using the following databases: CENTRAL (including Cochrane Eyes and Vision Trials Register; The Cochrane Library: Issue 2 of 12 February 2019), Ovid MEDLINE (R) without Revisions (1996 to February week 2, 2019), Ovid MEDLINE (R) (1946 to February week 2, 2019), Ovid MEDLINE (R) Daily Update 19 February 2019, MEDLINE and MEDLINE non-indexed items, Embase (1980–2019, week 7), Embase (1974–2019, 19 February), Ovid MEDLINE (R) and Epub Ahead of Print, in-Process & Other Non-Indexed Citations and Daily (1946 to 19 February 2019), Web of Science (all years), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov) and the WHO International Clinical Trials Registry Platform (www.who.int/ictrp/search/en). Only published articles in English were selected. Search terms/keywords included ‘IOL’ or ‘intraocular lens’, combined with ‘opacification’, degradation, glistenings, nanoglistenings, whitening, transmittance, light scatter, discolouration/discoloration, performance, quality, material, biocompatibility, calcification, explantation and ultraviolet/UV radiation. Relevant in-article references not returned in our searches were also considered. Results: After review of the available articles, the authors included 122 publications in this review, based on the quality of their methodology and their originality. The studies included in this review were randomized controlled trials, cohort studies, case-controlled studies, case series, case reports, laboratory studies and review papers. Differing material degradations of intraocular lenses have been described and their associated pathophysiology studied. Reported anomalies include photochemical alterations, water vacuoles, internal and surface calcific deposits, surface coatings and discolouration. The nature of such changes has been shown to depend on the type of intraocular lenses material used and/or manufacturing processes and storage conditions employed. Changes in the intraocular lens can also be influenced by surgical technique, coexisting ocular pathologies and topical and systemic medications. The clinical significance of these degradations is variable, with some resulting in significant visual disturbance and the need for intraocular lens explantation and others producing only minimal visual impairments. Failure to recognize the precise nature of the problem may lead to unnecessary laser capsulotomy procedures. Conclusion: Clinical degradations of intraocular lenses are uncommon but have been reported following the implantation of intraocular lenses made of differing biomaterials. Their correct identification and thorough investigation to determine the underlying cause is necessary for optimal patient management and the prevention of such problems. Choosing a lens made of a particular material may be important in patients with certain ocular conditions

Effects of intraocular lens glistenings on visual function: A prospective study and presentation of a new glistenings grading methodology

Objective To investigate the effect of intraocular lens (IOL) glistenings on visual performance and evaluate a new glistenings grading methodology. Methods and Analysis Thirty-four patients (34 eyes) were recruited. Corrected distance visual acuity (CDVA), mesopic gap acuity (MGA), functional contrast sensitivity (FCS) and forward light scatter were measured (Advanced Vision and Optometric Tests, City Occupational, London, UK). The IOL centre was imaged and glistenings density graded by three observers using the Miyata scale and a new system. Inter-rater reliability, association between the two grading scales, and correlations between glistenings grades and visual performance parameters were evaluated. Results The intraclass correlation coefficient between graders for the new grading system was 0.769 (95% Confidence Interval [CI] 0.636 to 0.868). There was a significant association between the Miyata scale and the new grading system for all graders (r s =0.533-0.895, p≤0.001). There was no association between CDVA or MGA and glistenings grade (r s =- 0.098, p=0.583 and r s =0.171, p=0.359, respectively). There was no association between FCS at mesopic light levels and glistenings grade (r s =-0.032, p=0.864), or the straylight parameter and glistenings grade (r s =0.021, p=0.916). No association was found between the integrated straylight parameter and glistenings grade (r s =0.078, p=0.701). Conclusion The new glistenings grading scale was highly reproducible. In this cohort, glistenings in the same hydrophobic acrylic IOL after cataract surgery were not associated with changes in visual function, as assessed by a series of tests not previously used in glistenings research

A new software for automated counting of glistenings in intraocular lenses in vivo

AIM: To assess the performance of a bespoke software for automated counting of intraocular lens (IOL) glistenings in slit-lamp images. METHODS: IOL glistenings from slit-lamp-derived digital images were counted manually and automatically by the bespoke software. The images of one randomly selected eye from each of 34 participants were used as a training set to determine the threshold setting that gave the best agreement between manual and automatic grading. A second set of 63 images, selected using randomised stratified sampling from 290 images, were used for software validation. The images were obtained using a previously described protocol. Software-derived automated glistenings counts were compared to manual counts produced by three ophthalmologists. RESULTS: A threshold value of 140 was determined that minimised the total deviation in the number of glistenings for the 34 images in the training set. Using this threshold value, only slight agreement was found between automated software counts and manual expert counts for the validating set of 63 images (κ=0.104, 95%CI, 0.040-0.168). Ten images (15.9%) had glistenings counts that agreed between the software and manual counting. There were 49 images (77.8%) where the software overestimated the number of glistenings. CONCLUSION: The low levels of agreement show between an initial release of software used to automatically count glistenings in in vivo slit-lamp images and manual counting indicates that this is a non-trivial application. Iterative improvement involving a dialogue between software developers and experienced ophthalmologists is required to optimise agreement. The results suggest that validation of software is necessary for studies involving semi-automatic evaluation of glistenings

The Transcription Factor SOX18 Regulates the Expression of Matrix Metalloproteinase 7 and Guidance Molecules in Human Endothelial Cells

Mutations in the transcription factor SOX18 are responsible for specific cardiovascular defects in humans and mice. In order to gain insight into the molecular basis of its action, we identified target genes of SOX18 and analyzed one, MMP7, in detail.SOX18 was expressed in HUVEC using a recombinant adenoviral vector and the altered gene expression profile was analyzed using microarrays. Expression of several regulated candidate SOX18 target genes was verified by real-time PCR. Knock-down of SOX18 using RNA interference was then used to confirm the effect of the transcription factor on selected genes that included the guidance molecules ephrin B2 and semaphorin 3G. One gene, MMP7, was chosen for further analysis, including detailed promoter studies using reporter gene assays, electrophoretic mobility shift analysis and chromatin-immunoprecipitation, revealing that it responds directly to SOX18. Immunohistochemical analysis demonstrated the co-expression of SOX18 and MMP7 in blood vessels of human skin.The identification of MMP7 as a direct SOX18 target gene as well as other potential candidates including guidance molecules provides a molecular basis for the proposed function of this transcription factor in the regulation of vessel formation

Correlation of LNCR rasiRNAs Expression with Heterochromatin Formation during Development of the Holocentric Insect Spodoptera frugiperda

Repeat-associated small interfering RNAs (rasiRNAs) are derived from various genomic repetitive elements and ensure genomic stability by silencing endogenous transposable elements. Here we describe a novel subset of 46 rasiRNAs named LNCR rasiRNAs due to their homology with one long non-coding RNA (LNCR) of Spodoptera frugiperda. LNCR operates as the intermediate of an unclassified transposable element (TE-LNCR). TE-LNCR is a very invasive transposable element, present in high copy numbers in the S. frugiperda genome. LNCR rasiRNAs are single-stranded RNAs without a prominent nucleotide motif, which are organized in two distinct, strand-specific clusters. The expression of LNCR and LNCR rasiRNAs is developmentally regulated. Formation of heterochromatin in the genomic region where three copies of the TE-LNCR are embedded was followed by chromatin immunoprecipitation (ChIP) and we observed this chromatin undergo dynamic changes during development. In summary, increased LNCR expression in certain developmental stages is followed by the appearance of a variety of LNCR rasiRNAs which appears to correlate with subsequent accumulation of a heterochromatic histone mark and silencing of the genomic region with TE-LNCR. These results support the notion that a repeat-associated small interfering RNA pathway is linked to heterochromatin formation and/or maintenance during development to establish repression of the TE-LNCR transposable element. This study provides insights into the rasiRNA silencing pathway and its role in the formation of fluctuating heterochromatin during the development of one holocentric organism

Novel features of ARS selection in budding yeast Lachancea kluyveri

<p>Abstract</p> <p>Background</p> <p>The characterization of DNA replication origins in yeast has shed much light on the mechanisms of initiation of DNA replication. However, very little is known about the evolution of origins or the evolution of mechanisms through which origins are recognized by the initiation machinery. This lack of understanding is largely due to the vast evolutionary distances between model organisms in which origins have been examined.</p> <p>Results</p> <p>In this study we have isolated and characterized autonomously replicating sequences (ARSs) in <it>Lachancea kluyveri </it>- a pre-whole genome duplication (WGD) budding yeast. Through a combination of experimental work and rigorous computational analysis, we show that <it>L. kluyveri </it>ARSs require a sequence that is similar but much longer than the ARS Consensus Sequence well defined in <it>Saccharomyces cerevisiae</it>. Moreover, compared with <it>S. cerevisiae </it>and <it>K. lactis</it>, the replication licensing machinery in <it>L. kluyveri </it>seems more tolerant to variations in the ARS sequence composition. It is able to initiate replication from almost all <it>S. cerevisiae </it>ARSs tested and most <it>Kluyveromyces lactis </it>ARSs. In contrast, only about half of the <it>L. kluyveri </it>ARSs function in <it>S. cerevisiae </it>and less than 10% function in <it>K. lactis</it>.</p> <p>Conclusions</p> <p>Our findings demonstrate a replication initiation system with novel features and underscore the functional diversity within the budding yeasts. Furthermore, we have developed new approaches for analyzing biologically functional DNA sequences with ill-defined motifs.</p

A transcriptomic analysis of Echinococcus granulosus larval stages:implications for parasite biology and host adaptation

The cestode Echinococcus granulosus--the agent of cystic echinococcosis, a zoonosis affecting humans and domestic animals worldwide--is an excellent model for the study of host-parasite cross-talk that interfaces with two mammalian hosts. To develop the molecular analysis of these interactions, we carried out an EST survey of E. granulosus larval stages. We report the salient features of this study with a focus on genes reflecting physiological adaptations of different parasite stages.We generated ~10,000 ESTs from two sets of full-length enriched libraries (derived from oligo-capped and trans-spliced cDNAs) prepared with three parasite materials: hydatid cyst wall, larval worms (protoscoleces), and pepsin/H(+)-activated protoscoleces. The ESTs were clustered into 2700 distinct gene products. In the context of the biology of E. granulosus, our analyses reveal: (i) a diverse group of abundant long non-protein coding transcripts showing homology to a middle repetitive element (EgBRep) that could either be active molecular species or represent precursors of small RNAs (like piRNAs); (ii) an up-regulation of fermentative pathways in the tissue of the cyst wall; (iii) highly expressed thiol- and selenol-dependent antioxidant enzyme targets of thioredoxin glutathione reductase, the functional hub of redox metabolism in parasitic flatworms; (iv) candidate apomucins for the external layer of the tissue-dwelling hydatid cyst, a mucin-rich structure that is critical for survival in the intermediate host; (v) a set of tetraspanins, a protein family that appears to have expanded in the cestode lineage; and (vi) a set of platyhelminth-specific gene products that may offer targets for novel pan-platyhelminth drug development.This survey has greatly increased the quality and the quantity of the molecular information on E. granulosus and constitutes a valuable resource for gene prediction on the parasite genome and for further genomic and proteomic analyses focused on cestodes and platyhelminths