Interaction between Metformin, Folate and Vitamin B12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies.

Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of 'catch up' growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin's transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes.

Quantification of the surgically induced refractive effect of intrastromal corneal ring segments in keratoconus with standardized incision site and segment size.

PURPOSE: To determine the surgically induced refractive and keratometric effects of intrastromal corneal ring segments (ICRS). SETTING: St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom. DESIGN: Case series. METHODS: Keratoconic patients had implantation of 2 vertically aligned 0.3 mm Intacs ICRS with the incision site at 90 degrees. Principal outcome measures were changes in visual acuity and refractive and keratometric effects (analyzed using methods of Kaye and Harris) 4 months postoperatively. Subgroup analysis was based on the Krumeich classification. RESULTS: Twenty-nine eyes (29 patients) were included. There was a significant difference between the mean preoperative (-5.16 +1.93 × 162.05) and postoperative (-2.64 +1.07 × 137.25) refractive errors (P=.01), with a mean refractive surgical effect of +1.35 +1.48 × 88.71 (SD +2.76 +4.78 × 149.62), and between the mean preoperative (51.32/2.28 @ 122.33) and postoperative (48.23/2.36 @ 92.10) keratometric powers (P=.001), with a mean keratometric surgical effect of -3.87/2.54 @ 61.77 (SD 1.37/4.20 @ 136). The irregularity index in the 3.0 mm zone decreased from 11.56 diopters (D) to 8.78 D. Refractive and keratometric surgical effects showed little difference within stages I through III and were greater in stage IV. CONCLUSIONS: Placement of two 0.3 mm ICRS caused overall flattening of the cornea (2.00 D to 3.00 D), with more flattening orthogonal to the incision site at 90 degrees. Variability of this effect, principally in the steep and flat meridians, limited the predictability of ICRS. Corneal behavior may differ with other incision sites. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

The psychosocial effects of strabismus: effect of patient demographics on the AS-20 score.

PURPOSE: The introduction of the AS-20 strabismus-specific quality-of-life questionnaire allows clinicians to quantify the effects of strabismus on adults for the first time. We correlated strabismic patients' demographic and clinical findings to their AS-20 scores. METHODS: A consecutive cohort of patients from an ongoing prospective study of adults with manifest strabismus was recruited. The patients' age, sex, socioeconomic status (SES), magnitude, and direction of deviation were correlated to their AS-20 scores. Patients' zip codes were used to derive a score for their SES based on the English 2007 Index of Multiple Deprivation score (IMD2007). RESULTS: A total of 61 questionnaires with all demographic and clinical data were available. The median magnitude of deviation was 20.4(Δ) in this group. The mean AS-20 score was 49.5 (SD 21.6). Women had significantly lower AS-20 scores than men (p = 0.02). There was no difference in AS-20 scores between individuals with eso- and exodeviations (p = 0.7). Multiple linear regression analysis shows female sex and lower SES to be significantly associated with lower AS-20 scores (p = 0.03 and p = 0.006, respectively). CONCLUSIONS: Strabismic patients who are female or live in a more deprived area have a significantly lower AS-20 score.

Ketamine and botulinum: a safe combinationfor the management of childhood strabismus.

AIMS: To determine the prevalence of ketamine side effects in children receiving botulinum toxin injections for strabismus under ketamine anesthesia and to establish the prevalence, severity, and duration of ptosis in these children. METHODS: Children who had undergone ketamine anesthesia for botulinum toxin injections (1999 to 2006) to correct strabismus were identified in a retrospective review. A questionnaire to establish occurrence of nightmares, sleepless nights, hallucinations (ketamine side effects), or ptosis (botulinum toxin side effect), was sent to parents or guardians. Details of side effects were obtained by telephone and the patients' medical records were analyzed. RESULTS: Questionnaires were sent to 113 patients (total of 130 injections). Ninety-seven (114 injections) completed questionnaires were returned. Emergence reactions were experienced by 12 patients (12.4%). Two children experienced sleepless nights, nightmares, and hallucinations. The remaining 10 experienced one side effect only. Eighteen children had ptosis at their 2-week follow-up appointment, most which resolved within 6 weeks. There were no life-threatening or sight-threatening adverse events. CONCLUSIONS: Botulinum toxin injection under intravenous ketamine anesthesia can safely be used for children. Ketamine anesthesia may be associated with side effects, namely hallucinations and sleep disturbances.

The psychosocial aspects of strabismus: correlation between the AS-20 and DAS59 quality-of-life questionnaires.

PURPOSE: To compare two quality-of-life (QoL) scales and subscales: the Derriford Appearance Scale 59 (DAS59) and the Adult Strabismus-20 (AS-20) scale in a series of strabismic and nonstrabismic patients and to illustrate the differences in results between strabismic and nonstrabismic patients. METHODS: The DAS59 is a self-report QoL questionnaire generating an assessment of distress caused by problems of appearance. The AS-20 is a newly developed strabismus specific QoL scale. A prospective, noninterventional study of a series of consecutive adult patients undergoing strabismus surgery and a control group was performed. Patients were given both questionnaires to complete before surgery. The underlying condition, previous number of surgeries, and deviation measurements were recorded. RESULTS: Thirty-four patients and 30 controls correctly completed both questionnaires. In the strabismus group, the mean AS-20 score was 50.5. The mean DAS59 score was 122.5 (out of 269). There is strong correlation between the scales (r = -0.813; 95% CI, -0.90 to -0.66; p < 0.0001). In the control group, the AS-20 score was 98.8 and the DAS59, 84.4, with both showing significant differences to the strabismic group (t = 12.9 [p < 0.0001] and t = -4.642 [p < 0.0001], respectively). CONCLUSIONS: The AS-20 shows strong correlation to the widely used DAS59. Strabismus patients show significantly more psychosocial distress than controls. The AS-20 is specific to strabismus patients and the result is not influenced by any other systemic factors that can impinge on the more general DAS59 scale.

Modified Lundie loops improve apraxia of eyelid opening.

BACKGROUND: Current treatments are unsatisfactory for improving apraxia of eyelid opening, defined as a delay or inability to open closed eyelids voluntarily in the presence of intact motor pathways. METHODS: Improvement in functional health was assessed using the Blepharospasm Disability Scale (BDS) in five consecutive patients with apraxia of eyelid opening treated with wire loops affixed behind ordinary spectacles (Lundie loops) and modified to provide pressure on the brow as a stimulus to keep the eyelids elevated. RESULTS: All five patients showed improvement in BDS scores. The mean percentage of normal activity of the study population improved from 25% to 37.6%. Outdoor activities were not significantly altered with the use of the device. CONCLUSIONS: Modified Lundie loops appear to be helpful in improving the functional health of patients with eyelid apraxia. These results will need to be verified in larger trials.