Eye Size and Shape in Relation to Refractive Error in Children: A Magnetic Resonance Imaging Study.

Purpose: The purpose of this study was to determine the association between eye shape and volume measured with magnetic resonance imaging (MRI) and optical biometry and with spherical equivalent (SE) in children. Methods: For this study, there were 3637 10-year-old children from a population-based birth-cohort study that underwent optical biometry (IOL-master 500) and T2-weighted MRI scanning (height, width, and volume). Cycloplegic refractive error was determined by automated refraction. The MRI images of the eyes were segmented using an automated algorithm combining atlas registration with voxel classification. Associations among optical biometry, anthropometry, MRI measurements, and RE were tested using Pearson correlation. Differences between refractive error groups were tested using ANOVA. Results: The mean volume of the posterior segment was 6350 (±680) mm3. Myopic eyes (SE ≤ -0.5 diopters [D]) had 470 mm3 (P < 0.001) and 970 mm3 (P < 0.001) larger posterior segment volume than emmetropic and hyperopic eyes (SE ≥ +2.0D), respectively. The majority of eyes (77.1%) had an oblate shape, but 47.4% of myopic eyes had a prolate shape versus 3.9% of hyperopic eyes. The correlation between SE and MRI-derived posterior segment length (r -0.51, P < 0.001) was stronger than the correlation with height (r -0.30, P < 0.001) or width of the eye (r -0.10, P < 0.001). Conclusions: In this study, eye shape at 10 years of age was predominantly oblate, even in eyes with myopia. Of all MRI measurements, posterior segment length was most prominently associated with SE. Whether eye shape predicts future myopia development or progression should be investigated in longitudinal studies.

Time Spent Outdoors Partly Accounts for the Effect of Education on Myopia.

Purpose: The purpose of this study was to investigate if education contributes to the risk of myopia because educational activities typically occur indoors or because of other factors, such as prolonged near viewing. Methods: This was a two-sample Mendelian randomization study. Participants were from the UK Biobank, Avon Longitudinal Study of Parents and Children, and Generation R. Genetic variants associated with years spent in education or time spent outdoors were used as instrumental variables. The main outcome measures were: (1) spherical equivalent refractive error attained by adulthood, and (2) risk of an early age-of-onset of spectacle wear (EAOSW), defined as an age-of-onset of 15 years or below. Results: Time spent outdoors was found to have a small genetic component (heritability 9.8%) that tracked from childhood to adulthood. A polygenic score for time outdoors was associated with children's time outdoors; a polygenic score for years spent in education was inversely associated with children's time outdoors. Accounting for the relationship between time spent outdoors and myopia in a multivariable Mendelian randomization analysis reduced the size of the causal effect of more years in education on myopia to -0.17 diopters (D) per additional year of formal education (95% confidence interval [CI] = -0.32 to -0.01) compared with the estimate from a univariable Mendelian randomization analysis of -0.27 D per year (95% CI = -0.41 to -0.13). Comparable results were obtained for the outcome EAOSW. Conclusions: Accounting for the effects of time outdoors reduced the estimated causal effect of education on myopia by 40%. These results suggest about half of the relationship between education and myopia may be mediated by children not being outdoors during schooling.

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration.

BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24). INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).

Myopia risk behaviour related to the COVID-19 lockdown in Europe: The generation R study.

PURPOSE: To battle the spreading of the COVID-19 virus, nationwide lockdowns were implemented during 2020 and 2021. Reports from China revealed that their strict home confinements led to an increase in myopia incidence. The Netherlands implemented a more lenient lockdown, which allowed children to go outside. We evaluated the association between COVID-19 restrictions, myopia risk behaviour and myopia progression in Dutch teenagers. METHOD: A total of 1101 participants (mean age 16.3 ± 3.65 yrs) completed questionnaires about their activities before, during and after lockdown (March-October 2020). We used a repeated-measures ANOVA to compare time use between these time periods. Ocular measurements were acquired before the COVID-19 pandemic when participants were 13 years old; only 242 participants had ocular measurements at 18 years of age at the time of this analysis. Linear regression analyses were used to evaluate the association between lifestyle factors and myopia progression. RESULTS: Children were on average 16.2 (1.03) years of age during lockdown. Total nearwork increased from 8.11 h/day to 11.79 h/day, and remained higher after lockdown at 9.46 h/day (p < 0.001). Non-educational nearwork increased by 2.22 h/day (+49%) during lockdown and was associated with faster axial length progression (B 0.002 mm/h/year; SE 0.001 p = 0.03). Before and during lockdown, the mean time spent outdoors was similar (1.78 h/day and 1.80 h/day, respectively). After lockdown, time spent outdoors decreased to 1.56 h/day (p < 0.001). CONCLUSION: The Dutch lockdown significantly increased digitised nearwork in adolescents but did not affect outdoor exposure. The changes in time spent performing nearwork remained after the lockdown measures had ended. We expect that the COVID-19 pandemic may lead to an increase in myopia prevalence and progression in European children.

Spatiotemporal expression of angiogenesis growth factor receptors during the revascularization of regenerating rat liver.

Regenerating liver was evaluated for the spatiotemporal expression of angiogenic growth factor receptors on endothelial cell (EC) membranes during revascularization resulting from 70% partial hepatectomy (PHx). Fractions enriched in EC membranes were examined by Western blot for angiogenic growth factor receptor expression from 1 to 14 days after PHx. Increases in vascular endothelial growth factor (VEGF) receptors Flt-1 and Flk-1/KDR, angiopoietin receptors Tie-1, Tie-2, and platelet-derived growth factor receptor beta (PDGF-Rbeta), modest increases in epidermal growth factor receptor (EGF-R), and no increase in hepatocyte growth factor receptor (c-Met) or fibroblast growth factor receptors (FGF-R) were observed in isolated membranes during EC proliferation. All receptors were tyrosine phosphorylated, and therefore activated, during peak expression. Immunofluorescence staining of regenerating liver identified populations with increased receptor expression, indicating cells receptive to ligand signaling. EGF-R was upregulated evenly throughout the sinusoidal membrane, whereas c-Met was observed on hepatocyte canaliculae, bile duct epithelium, and large vessel EC. Tie-2 and PDGF-Rbeta were increased on sinusoidal and large vessel EC, whereas Tie-1 was expressed in EC surrounding avascular hepatic islands. Flk-1/KDR was increased on large vessels with slight increases on sinusoidal EC, whereas Flt-1 was increased in arterioles, sinusoidal EC as well as in hepatocytes. Although Flt-1 was phosphorylated on isolated hepatocytes, vascular endothelial growth factor(165) (VEGF(165)) did not induce a proliferative or motogenic response. Proliferation assays on isolated EC indicated responsiveness to VEGF(165), but synergism among several growth factors including PDGF-BB was also observed. The data identify novel autocrine and paracrine interactions and indicate that each growth factor acts on a specific set of EC at specific times during revascularization of regenerating liver.

Abruptio placentae after auto accidents. A case-control study.

OBJECTIVE: To compare accident and injury characteristics in pregnant women with and without abruptio placentae involved in auto accidents (AAs). STUDY DESIGN: A retrospective, case-control study involving 12 pregnant women (16-39 weeks) with a diagnosis of abruptio placentae after AAs and 12 control subjects matched for gestational age (+/- 2 weeks) involved in AAs without abruptio placentae from 1988 through 1997. Numerous variables were compared, including restraint system use, estimated speed of the collision, injury severity score (ISS), clinical findings and patient position in the vehicle. Patient complaints and physical examination on admission were also recorded, and obstetric and neonatal outcomes were compared. Statistical analysis was performed using the independent sample t, Mann-Whitney and Fisher's exact tests, when appropriate. RESULTS: There was no significant difference in the frequency of unrestrained subjects or position in the vehicle between cases and controls. Estimated speed of the vehicle at the time of collision was significantly higher in the abruptio placentae group (> 30 mph, 92% vs. 50%, P = .03), as was the mean ISS code (20 [SD 12.71] vs. 4 [SD 5.13], P < .001). Abdominal pain and vaginal bleeding were seen more frequently in women with abruptio placentae as compared to controls (58% vs. 25% and 33% vs. 0, respectively). Patients with abruptio placentae had a higher incidence of preterm delivery (mean gestational age at delivery = 29 weeks [SD 7.99] vs. 36 weeks [SD 7.21], P = .008) and stillbirth (57% vs. 0%, P = .002) and lower mean birth weight (1,924 g [SD 931] vs. 3,069 g [SD 450], P = .003). There was no significant difference in cesarean section rates between the groups (58% vs. 30%, P = .23). There was no difference in the two groups in placental location on ultrasonography. CONCLUSION: Pregnant women who were involved in severe accidents (i.e., higher speed or ISS) were more likely to suffer abruptio placentae. In severe accidents, proper restraints were frequently not used. Because of the severity of these accidents, current restraint systems may not be sufficient to prevent abruptio placentae even with proper restraint use. Efforts toward designing new restraint systems for pregnant women should be encouraged.

Effects of cocaine on the placenta.

Adverse perinatal outcomes of gravidas using cocaine is well documented, but the effects on the placenta have been difficult to elucidate due to confounding factors such as concurrent use of other drugs. This study compares pathologic findings of 26 placentas from women who used only cocaine during pregnancy with findings from 26 controls. All women were from a similar socioeconomic class and were controlled for gestational age and tobacco use. None of the cocaine placentas were from women whose toxicology screens were positive for drugs other than cocaine. In the 26 cocaine placentas, there was 1 infarct, 3 chronic villitis, and 1 segmental fibrosis, with none present in the controls. In the control group, there was 1 decidual vasculopathy and 1 thrombus in a maternal vessel, but none were in the cocaine placentas. Each group had 1 thrombus in a fetal vessel. The study group showed 6 cases of chorioamnionitis and 1 funisitis; the control group had 10 and 4 cases, respectively. None of the above or seven other features showed a statistically significant difference between the cases and controls. Cocaine is a potent vasoconstrictive agent that blocks re-uptake of norepinephrine at the adrenergic nerve terminals. Our study suggests that cocaine does not cause an increased incidence of any of the 15 clearly recognizable placental features examined.

Candida funisitis: A clinicopathologic study of 32 cases.

We report on 32 cases of Candida funisitis and describe the associated clinicopathologic features. The Candida funisitis was characterized grossly by small, circumscribed, yellow-white nodules on the umbilical cord surface and, microscopically, by subamnionic microabscesses in which fungal organisms were demonstrable. Chorioamnionitis was present in all cases. Twenty-four (75%) of the 32 infants were premature. There were 7 perinatal deaths, all in immature fetuses. Five (16%) of the 32 fetuses had congenital candidiasis. Five (16%) of the mothers had a history of intrauterine foreign body, including intrauterine contraceptive device in three and cervical cerclage in two. The diagnosis of Candida funisitis should prompt a careful examination for fetal infection, even though it is associated with congenital candidiasis in only a minority of the cases.

Risk factors for recurrence of hemorrhagic endovasculitis of the placenta.

OBJECTIVE: To assess the potential for recurrence of placental hemorrhagic endovasculitis and to identify clinical or pathologic cofactors that might influence recurrence of this lesion or subsequent pregnancy outcome. METHODS: Ninety-seven women with a placenta affected by hemorrhagic endovasculitis, who also had at least one placenta referred to the Michigan Placental Tissue Registry from a subsequent pregnancy, were identified from 10,531 referrals between 1978 and 1988. Histologic slides from 209 placentas and clinical data from 211 infants (two sets of twins) from initial (first) and subsequent referrals were analyzed. Placentas were graded for the presence, extent, and severity of hemorrhagic endovasculitis and chronic villitis of unknown etiology; for placental lesions indicative of hypertensive maternal vessel disease; and for intravascular nucleated erythrocytes and chorionic thrombi. Maternal data included age, gravidity, number of previous losses, and history of toxemia or hypertension. All data were analyzed for significance using chi2 and t tests. Outcome assessment was based on recurrence of hemorrhagic endovasculitis and infant viability with the second referral. RESULTS: With first referrals, 80 of 98 infants (81.6%) were stillborn. Among second referrals, 26 of 98 infants (26.5%) were stillborn. Hemorrhagic endovasculitis recurred in 28 second placentas (28.9%); of these, 18 infants (64.3%) were stillborn. Higher rates of recurrence were found with progressively higher first-referral chronic villitis severity scores (P < .02), higher hypertensive placental lesion scores (P < .001), and first referrals with a history of toxemia or hypertension (P < .02). Recurrence of hemorrhagic endovasculitis was higher in patients with two or more of these factors in first referrals (P < .001). Subsequent stillbirth was more frequent with progressively higher first-referral hypertensive placental lesion scores (P < .01) and in first placentas with two or more risk factors (P = .064). Hemorrhagic endovasculitis severity scores, intravascular nucleated erythrocytes, and chorionic thrombi were associated with stillbirth in index pregnancies only. Maternal age, gravidity, or history of prior losses were not predictive. CONCLUSIONS: Placental hemorrhagic endovasculitis is associated with pregnancy loss and can recur in some patients. Interrelations among placental hemorrhagic endovasculitis, chronic villitis, maternal hypertension, and adverse outcomes in subsequent pregnancies are apparent. This information may be useful in patient counseling.

Angiomatous malformation of placental chorionic stem vessels and pseudo-partial molar placentas: report of five cases.

Five placentas referred to the Michigan Placental Tissue Registry between 1982 and 1992 exhibited an unusual malformation of chorionic stem vessels. Multiple intestine-like tangles arising from umbilical vessels rested on and entered the chorionic plate. This anomaly appears similar to the "unusual vascular anomaly of the placenta" reported by Lee et al. (Am J Clin Pathol 1991; 95:48-51). In addition, amnionic-type bands were often adherent to the vascular complex. In three cases, clusters of macrocystic villi interspersed by normal placental parenchyma resulted in a partial molar appearance. Two of the infants were stillborn; three were liveborn. Congenital anomalies were not recognized in other organs. Flow cytometric analysis of placental tissue from four specimens disclosed a diploid chromosomal pattern. This rare anomaly complex appears to be a malformation involving the extraembryonic mesoderm rather than a cytogenetic error.

Report of fourteen cases of nonimmune hydrops fetalis in association with hemorrhagic endovasculitis of the placenta.

Hemorrhagic endovasculitis of the placenta is a distinct vasodestructive process of unknown cause that has been associated with perinatal morbidity and mortality. A relationship between nonimmune hydrops fetalis and hemorrhagic endovasculitis has not been previously described. At a large teaching hospital, six cases of nonimmune hydrops fetalis were identified out of 72 cases of hemorrhagic endovasculitis over 6 years, for an incidence of 8%. Conversely, these same six cases represented 24% of the 25 cases of nonimmune hydrops fetalis from this time period. Eight additional cases of nonimmune hydrops fetalis were found among 2064 cases of hemorrhagic endovasculitis at the Michigan Placental Tissue Registry. In eight of the total 14 cases, after congenital malformations and cytomegalovirus infections were excluded, hemorrhagic endovasculitis was the only significant associated pathologic finding evident. The significance of the relationship between nonimmune hydrops fetalis and the vascular abnormalities of hemorrhagic endovasculitis remains to be determined.

The Michigan Placental Tissue Registry.

The Michigan Placental Tissue Registry is located in the Department of Pathology at Michigan State University in East Lansing. Operational since 1970, the registry now receives some 1300 specimens annually from Michigan, out-of-state, and out-of-country hospitals. This registry is intended to assist physicians with patient care, to maintain a tissue bank for referred specimens, and to explore the cause, clinical significance, and management of placental abnormalities.