Microbial rhodoquinone biosynthesis proceeds via an atypical RquA-catalyzed amino transfer from S-adenosyl-L-methionine to ubiquinone.

Rhodoquinone (RQ) is a close analogue of ubiquinone (UQ) that confers diverse bacterial and eukaryotic taxa the ability to utilize fumarate as an electron acceptor in hypoxic conditions. The RquA protein, identified in a Rhodospirillum rubrum RQ-deficient mutant, has been shown to be required for RQ biosynthesis in bacteria. In this report, we demonstrate that RquA, homologous to SAM-dependent methyltransferases, is necessary and sufficient to catalyze RQ biosynthesis from UQ in vitro. Remarkably, we show that RquA uses SAM as the amino group donor in a substitution reaction that converts UQ to RQ. In contrast to known aminotransferases, RquA does not use pyridoxal 5'-phosphate (PLP) as a coenzyme, but requires the presence of Mn2+ as a cofactor. As these findings reveal, RquA provides an example of a non-canonical SAM-dependent enzyme that does not catalyze methyl transfer, instead it uses SAM in an atypical amino transfer mechanism.

Pain Control Following Photorefractive Keratectomy: A Prospective Clinical Trial Comparing Codeine Versus Oxycodone for the Management of Postoperative Pain.

PURPOSE: To compare the efficacy of oral codeine plus acetaminophen versus oxycodone plus acetaminophen for severe pain control following photorefractive keratectomy (PRK). METHODS: This single-center trial randomized 200 patients to receive codeine 30 mg/acetaminophen 325 mg (codeine group) or oxycodone 5 mg/acetaminophen 325 mg (oxycodone group)every 4 hours as needed for severe pain for 4 days following PRK. Patients recorded postoperative pain, tablet consumption, and tetracaine use. Patients were monitored at postoperative 1 day, 1 week, and 1, 3, and 6 months for visual acuity and follow-up. Study outcomes were mean postoperative pain, treatment and tetracaine use, and visual acuity. RESULTS: Analysis of 197 patients who completed the trial (97 codeine group and 100 oxycodone group) showed mean pain scores were lower in the codeine group throughout the intervention period. Mean pain scores were higher in the oxycodone group than the codeine group on postoperative days 2 and 4 (P = .017 and P = .034, respectively). The oxycodone group consumed more tablets than the codeine group, with a difference on postoperative day 2 (P = .019), and used a greater number of tetracaine drops (P = .015). Repeated measures analysis of variance showed significant improvement in visual acuity in both groups with no difference in visual outcomes (P = .81). CONCLUSIONS: Codeine/acetaminophen is as effective and safe as oxycodone/acetaminophen for pain control following PRK, with no clinical difference in overall pain control and long-term visual outcomes. This implies that treating postoperative pain after PRK with a Schedule III opioid (codeine) is effective and potentially decreases the risk of misuse by a higher regulated Schedule II opioid (oxycodone), lowering the potential for abuse and dependence. [J Refract Surg. 2021;37(9):582-589.].

Retrospective Analysis of the Post-Operative Changes in Higher-Order Aberrations: A Comparison of the WaveLight EX500 to the VISX S4 Laser in Refractive Surgery.

INTRODUCTION: In an attempt to maximize treatment outcomes, refractive surgery techniques are being directed toward customized ablations to correct not only lower-order aberrations but also higher-order aberrations specific to the individual eye. Measurement of the entirety of ocular aberrations is the most definitive means to establish the true effect of refractive surgery on image quality and visual performance. Whether or not there is a statistically significant difference in induced higher-order corneal aberrations between the VISX Star S4 (Abbott Medical Optics, Santa Ana, California) and the WaveLight EX500 (Alcon, Fort Worth, Texas) lasers was examined. METHODS: A retrospective analysis was performed to investigate the difference in root-mean-square (RMS) value of the higher-order corneal aberrations postoperatively between two currently available laser platforms, the VISX Star S4 and the WaveLight EX500 lasers. The RMS is a compilation of higher-order corneal aberrations. Data from 240 total eyes of active duty military or Department of Defense beneficiaries who completed photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK) refractive surgery at the Wilford Hall Ambulatory Surgical Center Joint Warfighter Refractive Surgery Center were examined. Using SPSS statistics software (IBM Corp., Armonk, New York), the mean changes in RMS values between the two lasers and refractive surgery procedures were determined. A Student t test was performed to compare the RMS of the higher-order aberrations of the subjects' corneas from the lasers being studied. A regression analysis was performed to adjust for preoperative spherical equivalent. The study and a waiver of informed consent have been approved by the Clinical Research Division of the 59th Medical Wing Institutional Review Board (Protocol Number: 20150093H). RESULTS: The mean change in RMS value for PRK using the VISX laser was 0.00122, with a standard deviation of 0.02583. The mean change in RMS value for PRK using the WaveLight EX500 laser was 0.004323, with a standard deviation of 0.02916. The mean change in RMS value for LASIK using the VISX laser was 0.00841, with a standard deviation of 0.03011. The mean change in RMS value for LASIK using the WaveLight EX500 laser was 0.0174, with a standard deviation of 0.02417. When comparing the two lasers for PRK and LASIK procedures, the p values were 0.431 and 0.295, respectively. CONCLUSION: The results of this study suggest no statistically significant difference concerning induced higher-order aberrations between the two laser platforms for either LASIK or PRK. Overall, the VISX laser did have consistently lower induced higher-order aberrations postoperatively, but this did not reach statistical significance. It is likely the statistical significance of this study was hindered by the power, given the relatively small sample size. Additional limitations of the study include its design, being a retrospective analysis, and the generalizability of the study, as the Department of Defense population may be significantly different from the typical refractive surgery population in terms of overall health and preoperative refractive error. Further investigation of visual outcomes between the two laser platforms should be investigated before determining superiority in terms of visual image and quality postoperatively.

Dose Uniformity of Topical Corticosteroids: A Simulated Trial of Fluorometholone Acetate 0.1% and Loteprednol Etabonate Gel 0.5.

PURPOSE: The purpose of the study was to determine the concentrations of Flarex® and Lotemax® when shaken and not shaken. Many patients fail to shake or inappropriately shake suspensions of corticosteroids before instillation as directed. This study was designed to help determine what concentration of corticosteroid these patients are receiving. In addition, independent confirmation of loteprednol etabonate ophthalmic gel dose uniformity was determined and compared as a possible alternative. METHODS: Drug concentrations of shaken versus unshaken Flarex and Lotemax were determined over a 20-day simulated tapered course in our institutional laboratory. Collected samples were analyzed by reversed-phase high-performance liquid chromatography with photodiode array detection at 240 nm. RESULTS: Flarex had a mean concentration of 93.7% of the declared concentration when shaken and 7.25% when not shaken. The difference between these groups was statistically significant (P = 0.0001). Lotemax had a mean concentration of 96.74% of the declared concentration when shaken and a mean concentration of 98.97% when not shaken. The difference between these groups was not statistically significant (P = 0.194). CONCLUSIONS: Flarex maintains dose uniformity when shaken. When not shaken, it has poor dose uniformity. Lotemax was consistent whether shaken or not in our study and can be considered to eliminate the variability of poor patient compliance with shaking. The manufacturers of both drugs recommend shaking before application.

Comparison of pachymetry measurements between the Alcon Wavelight EX500 and Sonogage Corneo-Gage plus platforms.

PURPOSE: To compare the agreement of intraoperative central corneal thickness (CCT) measurements of the Wavelight EX500 (Alcon Laboratories, Fort Worth, TX) that uses optical low coherence reflectometry to the Corneo-Gage Plus ultrasound pachymetry device (Sonogage, Cleveland, OH). METHODS: In this retrospective study, 50 eyes of 26 patients undergoing LASIK were evaluated. Following LASIK flap creation, each eye was measured by both optical low coherence reflectometry and ultrasound pachymetry immediately prior to flap lifting and then again after flap lifting. RESULTS: The mean CCT value before lifting the flap was 556.9 and 557.78 µm as measured by ultrasound pachymetry and optical low coherence reflectometry, respectively. After lifting the flap, the mean ultrasound pachymetry value was 440.96 µm and the mean optical low coherence reflectometry value was 441.7 µm. A two-sample Kolmogorov-Smirnov test demonstrated that the ultrasound pachymetry and the optical low coherence reflectometry distribution of measurements were the same. A Shapiro-Wilk test of normality could not be rejected. Bland-Altman plots showed strong agreement. The correlation between the two tests was 0.98 before flap lifting and 0.97 after flap lifting, both with a 95% confidence interval. CONCLUSIONS: The pachymetry measurements by the optical low coherence reflectometry correlated with those of the ultrasound pachymetry device. The Wavelight EX500 optical low coherence reflectometry may be used in place of the ultrasound pachymetry device for measuring CCT.