Glare prediction and mechanism of adaptation following implantation of hydrophilic and hydrophobic intraocular lenses.

Purpose: Glare is a known side effect of intraocular lens (IOL) implantation, affected principally by IOL material and optics, although it is reported subjectively to decrease in impact with time. However, little objective data have been published on changes over time, how these relate to subjective reports, and whether those who will report greater glare symptoms can be predicted prior to IOL implantation. Methods: A total of 32 patients (aged 72.4 ± 8.0 years) with healthy eyes were implanted bilaterally with hydrophilic 600s (Rayner, Worthing, UK) or hydrophobic Acrysof (Alcon, Texas, USA) acrylic IOLs (n = 16 each, randomly assigned). Each patient reported their dysphotopsia symptoms subjectively using the validated forced choice photographic questionnaire for photic phenomena, and halo size resulting from a bright light in a dark environment was quantified objectively in eight orientations using the Aston Halometer. Assessment was performed binocularly pre-operatively and at 1, 2, 3, and 4 weeks after IOL implantation. Setting: The study was carried out at the National Health Service Ophthalmology Department, Queen Elizabeth Hospital, Birmingham, UK. Results: Visual acuity (average 0.37 ± 0.26 logMAR) did not correlate with subjective glare (r = 0.184, p = 0.494) or objective glare (r = 0.294, p = 0.270) pre-surgery. Objective halo size (F = 112.781, p < 0.001) decreased with cataract removal and IOL implantation and continued to decreased over the month after surgery. Subjective dysphotopsia complaints (p < 0.001) were also greater pre-surgery, but did not change thereafter (p = 0.228). In neither case was there a difference with IOL material (p > 0.05). It was not possible to predict post-surgery dysphotopsia from symptoms or a ratio of symptoms to halo size pre-surgery (p > 0.05). Conclusions: Subjective dysphotopsia and objective halos caused by cataracts are greatly reduced by implantation of IOL after cataract removal causing few perceivable symptoms. However, objective measures are able to quantify a further reduction in light scatter over the first month post-IOL implantation, suggesting that any subjective effects over this period are due to the healing process and not due to neuroadaptation.

Patterns of somatic mutation in human cancer genomes.

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.

Best technique for upper lid eversion.

AIM: Lid eversion is an essential component of contact lens aftercare. Hence, this study determined the best method of lid eversion based on three criteria: comfort, speed of administration and the area of the palpebral conjunctiva exposed. METHOD: Twenty-five participants (aged 20-34) had 6 different techniques applied in random order by the same clinician on two separate occasions: three involving a cotton bud placed on the extended upper eyelid either centrally, at the top of the tarsal plate or off-centre; one using the wooden end of the bud placed at the top of the tarsal plate; one using the clinician's index finger to evert the lid; and one using a silicone rubber, finger-shaped substitute. The participants judged the degree of discomfort of each technique on a visual analogue scale. The time to complete the task was timed with a stop-watch and the area of exposed palpebral conjunctiva was captured with a digital slit lamp and assessed using image analysis. RESULTS: There was no difference between the initial lid eversion or subsequent repeat in terms of comfort (F = 0.304, p = 0.586), time to complete (F = 3.075, p = 0.092) or area exposed (F = 2.311, p = 0.142). Lid eversion using fingers alone or the silicone substitute everter were similar in comfort (p = 0.312), being the most comfortable methods, with off-centre cotton bud eversion or the wooden end of the cotton bud the least comfortable techniques (F = 17.480, p < 0.001). The quickest method to perform was the wooden end of the cotton bud, followed by the silicone everter (F = 17.522, p < 0.001). The area of exposed palpebral conjunctiva was greatest using the silicone everter (F = 28.199, p < 0.001). CONCLUSIONS: Lid eversion had repeatable results, with the silicone everter placed at the top of the tarsal plate the most comfortable for the patient, quick to perform and exposed a greater area of tarsal plate than other techniques and therefore is recommended to clinicians.

Rotational Stability and Centration of a New Toric Lens Design Platform Using Objective Image Analysis Over 6 Months.

PURPOSE: To determine the rotational stability of the Rayner 600S intraocular lens (IOL) (Rayner, Worthing, United Kingdom) using objective image analysis techniques. METHODS: A total of 66 patients (mean age: 69.92 ± 8.45 years) with healthy eyes presenting for routine cataract surgery were implanted monocularly with the 600S IOL and followed up over 90 to 180 days postoperatively. Images of the IOL were captured through a maximally dilated pupil (tropicamide 1.0%, phenylephrine 2.5%) immediately after surgery and after 1 to 3 days, 30 days, and 90 to 180 days using a digital slit-lamp biomicro-scope. The orientation of the IOL markings were image analyzed compared to conjunctival blood vessel landmarks visible across all time points to correct for head and rotation. Centration was assessed by drawing ovals to circumscribe the IOL, pupil, and limbus to compare the centers (0.01 mm per-pixel resolution). RESULTS: Absolute values for rotation postoperatively were 1.60° ± 1.13° at 1 to 3 days, 1.58° ± 1.36° at 30 days, and 1.83° ± 1.44° at 90 to 180 days. No lens rotated more than 5°. The average centration relative to the limbus was -0.04 ± 0.25 mm horizontally and 0.04 ± 0.26 mm vertically at 1 to 3 days, 0.00 ± 0.38 mm vertically and 0.01 ± 0.28 mm horizontally at 30 days, and 0.08 ± 0.37 mm vertically and 0.07 ± 0.47 mm horizontally at 90 to 180 days. CONCLUSIONS: The Rayner 600S IOL showed exceptional rotational stability and centration after implantation, meeting the U.S. Food and Drug Administration prescribed American National Standards Institute standards for toric IOLs. [J Refract Surg. 2019;35(1):48-53.].

Metformin protects the ischemic heart by the Akt-mediated inhibition of mitochondrial permeability transition pore opening.

BACKGROUND: In the majority of studies, metformin has been demonstrated to cardioprotect diabetic patients, the mechanism of which is unclear. We hypothesized that metformin cardioprotects the ischemic heart through the Akt-mediated inhibition of mitochondrial permeability transition pore (mPTP) opening. MATERIALS AND METHODS: Isolated perfused hearts from normoglycemic Wistar or from diabetic Goto-Kakizaki (GK) rats (N > or = 6/group) were subjected to 35 min ischemia and 120 min of reperfusion. Metformin (50 micromol/l) was added for 15 min at reperfusion, alone or with LY294002 (15 micromol/l), a PI3K inhibitor. Infarct size and Akt phosphorylation were measured. Furthermore, the effect of metformin on mPTP opening in adult cardiomyocytes isolated from both strains was determined. RESULTS: Metformin reduced infarct size in both Wistar (35 +/- 2.7% metformin vs. 62 +/- 3.0% control: P < 0.05) and GK hearts (43 +/- 4.7% metformin vs. 60 +/- 3.8% control: P < 0.05). This protection was accompanied by a significant increase in Akt phosphorylation. LY294002 abolished the metformin-induced Akt phosphorylation and the infarct-limiting effect of metformin in Wistar (61 +/- 6.7% metformin + LY294002 vs. 35 +/- 2.7% metformin: P < 0.05) and GK rats (56 +/- 5.7% metformin + LY294002 vs. 43 +/- 4.7% metformin: P < 0.05). In addition, metformin significantly inhibited mPTP opening and subsequent rigor contracture in both Wistar and GK cardiomyocytes subjected to oxidative stress, in a LY-sensitive manner. CONCLUSIONS: We report that metformin given at the time of reperfusion reduces myocardial infarct size in both the non-diabetic and diabetic heart and this protective effect is mediated through PI3K and is associated with Akt phosphorylation. Furthermore, cardioprotection appears to be executed through a PI3K-mediated inhibition of mPTP opening. These findings may explain in part the cardioprotective properties of metformin observed in clinical studies of diabetic patients.