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Ascorbic acid metabolites are involved in intraocular pressure control in the general population.

ABSTRACT: Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Mechanisms involved in its homeostasis are not well understood, but associations between metabolic factors and IOP have been reported. To investigate the relationship between levels of circulating metabolites and IOP, we performed a metabolome-wide association using a machine learning algorithm, and then employing Mendelian Randomization models to further explore the strength and directionality of effect of the metabolites on IOP. We show that O-methylascorbate, a circulating Vitamin C metabolite, has a significant IOP-lowering effect, consistent with previous knowledge of the anti-hypertensive and anti-oxidative role of ascorbate compounds. These results enhance understanding of IOP control and may potentially benefit future IOP treatment and reduce vision loss from glaucoma.

SUBMITTER: Hysi PG

PROVIDER: S-EPMC6223183 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Ascorbic acid metabolites are involved in intraocular pressure control in the general population.

Hysi Pirro G PG Khawaja Anthony P AP Menni Cristina C Tamraz Bani B Wareham Nick N Khaw Kay-Tee KT Foster Paul J PJ Benet Leslie Z LZ Spector Tim D TD Hammond Chris J CJ

Redox biology 20181013

Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Mechanisms involved in its homeostasis are not well understood, but associations between metabolic factors and IOP have been reported. To investigate the relationship between levels of circulating metabolites and IOP, we performed a metabolome-wide association using a machine learning algorithm, and then employing Mendelian Randomization models to further explore the strength and directionality of effect of the metabol ...[more]

PMID: 30391827

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Project description:PurposeTo investigate the impact of intraocular pressure (IOP) control on rates of change of spectral-domain OCT (SD-OCT) retinal nerve fiber layer (RNFL) thickness in a large clinical population.DesignRetrospective cohort study.ParticipantsA total of 85 835 IOP measurements and 60 223 SD-OCT tests from 14 790 eyes of 7844 patients.MethodsData were extracted from the Duke Glaucoma Registry, a large database of electronic medical records of patients with glaucoma and suspected disease followed over time at the Duke Eye Center and satellite clinics. All records from patients with a minimum of 6 months of follow-up and at least 2 good-quality SD-OCT scans and 2 clinical visits with Goldmann applanation tonometry were included. Eyes were categorized according to the frequency of visits with IOP below cutoffs of 21 mmHg, 18 mmHg, and 15 mmHg over time. Rates of change for global RNFL thickness were obtained using linear mixed models and classified as slow if change was slower than -1.0 μm/year; moderate if between -1.0 and -2.0 μm/year; and fast if faster than -2.0 μm/year. Multivariable models were adjusted for age, gender, race, diagnosis, central corneal thickness, follow-up time, and baseline disease severity.Main outcome measuresRates of change in SD-OCT RNFL thickness according to levels of IOP control.ResultsEyes had a mean follow-up of 3.5±1.9 years. Average rate of change in RNFL thickness was -0.68±0.59 μm/year. Each 1 mmHg higher mean IOP was associated with 0.05 μm/year faster RNFL loss (P < 0.001) after adjustment for potentially confounding variables. For eyes that had fast progression, 41% of them had IOP <21 mmHg in all visits during follow-up, whereas 20% of them had all visits with IOP <18 mmHg, but only 9% of them had all visits with IOP <15 mmHg.ConclusionsIntraocular pressure was significantly associated with rates of progressive RNFL loss in a large clinical population. Eyes with stricter IOP control over follow-up visits had a smaller chance of exhibiting fast deterioration. Our findings may assist clinicians in establishing target pressures in clinical practice.

Project description:PurposeTo determine the effect of general anesthesia on intraocular pressure (IOP) in children with no intraocular pathology and determine which postanesthetic time point is most predictive of preinduction IOP.DesignProspective observational study.ParticipantsChildren with no intraocular pathology ≤ 18 years scheduled for general anesthesia as part of their routine care followed by a pediatric ophthalmologist at Nanjing Medical University.MethodsParticipants underwent a standardized general anesthetic protocol using a mask induction with sevoflurane and propofol maintenance. Intraocular pressure was measured at the following 7 time points: preinduction (taken in the preoperative area), postinduction minutes 1, 3, and 5, and postairway placement minutes 1, 3, and 5 for a total time period of 10 minutes after induction. A generalized estimating equation was used to evaluate the effect of anesthesia on IOP and the effect of patient factors (age, gender, vital signs, and airway type) on preanesthetic and postanesthetic IOP. An IOP prediction model was developed using the postanesthesia IOP measurements for predicting preinduction IOP.Main outcome measuresIntraocular pressure and change in IOP at prespecified time points.ResultsEighty-five children were enrolled with a mean ± standard deviation (SD) age of 7.5 ± 2.9 years. Mean ± SD preinduction IOP was 20.1 ± 3.7 mmHg. Overall, IOP was lowest at 3 minutes postinduction, decreased to a mean of 13.4 ± 3.7 mmHg (P < 0.001). After this, IOP rose 5 minutes postinduction to 16.5 ± 4.2 mmHg, which did not reach preinduction IOP levels (P < 0.001). The IOP prediction model showed that combining 1 minute postinduction and 3 minutes postairway was most predictive (R2 = 0.13), whereas 1 minute postairway was least predictive of preinduction IOP (R2 = 0.01).ConclusionsAfter the induction of general anesthesia in children, IOP temporarily decreases with a trough at 3 minutes postinduction before increasing and remaining stable just below preinduction levels. Intraocular pressure measurements taken 1 minute after induction with 3 minutes after airway placement are most predictive of preinduction IOP, though predictive value is relatively low.Financial disclosuresProprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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Ascorbic acid metabolites are involved in intraocular pressure control in the general population.

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Ascorbic acid metabolites are involved in intraocular pressure control in the general population.

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