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

Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

Hyperglycemia (HG) and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients

In vitro protein-DNA interactions at the human lamin B2 replication origin.

The complexity of mammalian origins of DNA replication has prevented, so far, the in vitro studies of the modalities of initiator protein binding and origin selection. We approached this problem by utilizing the human lamin B2 origin, wherein the precise start sites of replication initiation have been identified and known to be bound in vivo by the origin recognition complex (ORC). In order to analyze the in vitro interactions occurring at this origin, we have compared the DNA binding requirements and patterns of the human recombinant Orc4 with those of preparations of HeLa nuclear proteins containing the ORC complex. Here we show that both HsOrc4 alone and HeLa nuclear proteins recognize multiple sites within a 241-bp DNA sequence encompassing the lamin B2 origin. The DNA binding activity of HeLa cells requires the presence of ORC and can be reproduced in the absence of all the other proteins known to be recruited to origins by ORC. Both HsOrc4 alone and HeLa nuclear proteins exhibit cooperative and ATP-independent binding. This binding covers nucleotides 3853-3953 and then spreads outward. Because this region contains the start sites of DNA synthesis as well as the area protected in vivo and preserves protein binding capacity in vitro after removal of a fraction of the protected region, we suggest that it could contain the primary binding site. Thus the in vitro approach points to the sequence requirements for ORC binding as a key element for origin recognition

Single-molecule analysis reveals that DNA replication dynamics vary across the course of schizogony in the malaria parasite Plasmodium falciparum.

The mechanics of DNA replication and cell cycling are well-characterized in model organisms, but less is known about these basic aspects of cell biology in early-diverging Apicomplexan parasites, which do not divide by canonical binary fission but undergo unconventional cycles. Schizogony in the malaria parasite, Plasmodium, generates ~16-24 new nuclei via independent, asynchronous rounds of genome replication prior to cytokinesis and little is known about the control of DNA replication that facilitates this. We have characterised replication dynamics in P. falciparum throughout schizogony, using DNA fibre labelling and combing to visualise replication forks at a single-molecule level. We show that origins are very closely spaced in Plasmodium compared to most model systems, and that replication dynamics vary across the course of schizogony, from faster synthesis rates and more widely-spaced origins through to slower synthesis rates and closer-spaced origins. This is the opposite of the pattern usually seen across S-phase in human cells, when a single genome is replicated. Replication forks also appear to stall at an unusually high rate throughout schizogony. Our work explores Plasmodium DNA replication in unprecedented detail and opens up tremendous scope for analysing cell cycle dynamics and developing interventions targetting this unique aspect of malaria biology.The work was supported by UK Research Councils [MR/L008823/1, BB/K009206/1 to CJM]; by the Agence Nationale de la Recherche within the frame of the “Investissements d’avenir” program [ANR11-LABX-0024-01 “PARAFRAP” to YS], the Centre National de la Recherche Scientifique (CNRS) and the French Ministry of Research and the Centre Hospitalier Universitaire of Montpellier [YS]; the “Fondation pour la Recherche Médicale” (FRM) and Agence Nationale de la Recherche (ANR) [SS

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

Corneal astigmatic outcomes after femtosecond laser-assisted cataract surgery combined with surface penetrating arcuate keratotomies

AIM: To evaluate corneal astigmatic outcomes of femtosecond laser-assisted arcuate keratotomies (FAKs) combined with femtosecond-laser assisted cataract surgery (FLACS) over 12mo follow-up. METHODS: Totally 145 patients with bilateral cataracts and no ocular co-morbidities were recruited to a single-centre, single-masked, prospective randomized controlled trial (RCT) comparing two monofocal hydrophobic acrylic intraocular lenses. Eyes with corneal astigmatism (CA) of >0.8 dioptres (D) received unpaired, unopened, surface penetrating FAKs at the time of FLACS. Visual acuity, subjective refraction and Scheimpflug tomography were recorded at 1, 6, and 12mo. Alpins vectoral analyses were performed. RESULTS: Fifty-one patients (61 eyes), mean age 68.2±9.6y [standard deviation (SD)], received FAKs. Sixty eyes were available for analysis, except at 12mo when 59 attended. There were no complications due to FAKs. Mean pre-operative CA was 1.13±0.20 D. There was a reduction of astigmatism at all post-operative visits (residual CA 1mo: 0.85±0.42 D, P=0.0001; 6mo: 0.86±0.35 D, P=0001; and 12mo: 0.90±0.39, P=0.0001). Alpins indices remained stable over 12mo. Overall, the cohort was under-corrected at all time points. At 12mo, 61% of eyes were within ±15 degrees of pre-operative astigmatic meridian. CONCLUSION: Unpaired unopened penetrating FAKs combined with on-axis phacoemulsification are safe but minimally effective. CA is largely under-corrected in this cohort using an existing unmodified nomogram. The effect of arcuate keratotomies on CA remained stable over 12mo

Visual and refractive outcomes and glistenings occurrence after implantation of 2 monofocal, aspheric, hydrophobic acrylic IOLs

PURPOSE: To compare the Clareon intraocular lens (IOL) with the Tecnis PCB00 IOL in terms of visual performance, refractive outcomes, glistenings occurrence, and quality-of-life outcomes. SETTING: Guy's and St Thomas' NHS Foundation Trust, London, England. DESIGN: Single-center, single-masked, prospective, randomized, controlled trial. METHODS: One hundred thirty-nine patients with bilateral cataracts were randomized to receive the Clareon (C IOL) or Tecnis (T IOL) IOL. Visual acuity, refraction, central corneal thickness (CCT), endothelial cell loss, contrast sensitivity, and mesopic gap acuity, evaluation of glistenings and rates of perioperative and postoperative complications were recorded. Quality-of-life outcomes were measured with the EuroQOL-5 Dimension questionnaire and the Patient-Reported Outcome Measures questionnaire. Optimised A-constants were available for the T IOL but not the C IOL. RESULTS: Seventy-one patients (140 eyes) received the C IOL and 68 patients (134 eyes) received the T IOLs. Data were analysed for the first implanted eye. At 12 months, mean uncorrected distance visual acuity (logarithm of the minimum angle of resolution) was 0.02+/-0.10 and 0.01+/-0.08 (mean+/- SD; P=0.49; 95% CI -0.02, 0.04) in the C IOL and T IOL groups, respectively. Corrected visual acuity was -0.02+/-0.09 and -0.03+/-0.06, respectively (P=0.45; 95% CI -0.02, 0.04). The increase in CCT was 14+/-19 and 16+/-28 μm, respectively (P=0.63;95% CI -10.16, 6.16). Mean absolute refraction spherical equivalent error from target refraction was 0.41+/-0.28 for the C IOL and 0.25+/-0.2 for the T IOL groups (P=0.002; 95% CI 0.08, 0.24). Glistenings were minimal (median grade 0), with no difference in grades between groups (P=0.2). PROMS improved postoperatively and were similar in both groups. CONCLUSIONS: There were no differences in visual outcomes between the Clareon IOL and Tecnis PCB00 IOLs. Glistenings were rarely observed in either IOL with no difference in grades. There was no difference in perioperative or postoperative complications. Surgeon optimization of the A-constant for the Clareon IOL is recommended