Secondary developmental glaucoma in eyes with congenital aphakia

Purpose:To describe the clinical spectrum and management of glaucoma in congenital aphakia.Methods:The demographics and clinical spectrum of eyes with congenital aphakia with and without glaucoma were compared, and management outcomes of congenital aphakia cases with glaucoma were studied retrospectively between April 2000 and June 2020.Results:There were a total of 168 eyes (84 subjects) with a diagnosis of congenital aphakia, of which 29 eyes of 18 subjects were diagnosed with glaucoma. Corneal opacity was the presenting complaint in 26/29 eyes with glaucoma and 139/139 eyes without glaucoma. The (interquartile range (IQR)) horizontal corneal diameter was 10.5mm (IQR, 9.0-12.5) and 8mm (IQR, 5-10) in eyes with and without glaucoma (P = 0.01), respectively. The median (IQR) axial length was 17.5mm (IQR, 13.5-19.5) and 15mm (IQR, 14-16) mm in eyes with and without glaucoma (P = 0.03), respectively. Nineteen eyes with glaucoma had adequate intraocular pressure (IOP) control with one medication. Three eyes underwent transscleral diode cyclophotocoagulation and maintained IOP without medications. Three eyes underwent trabeculectomy and trabeculotomy, trabeculectomy followed by penetrating keratoplasty, and trabeculectomy, respectively, of which two eyes became phthisical. At the last follow-up, the median (IQR) IOP was 14 mm Hg (IQR, 14-17) Hg. The median (IQR) follow-up duration was 4.53 months (IQR, 2.03- 48.06).Conclusion:One-fifth of the eyes with congenital aphakia had secondary developmental glaucoma. The corneal diameter and axial lengths were higher in the eyes with glaucoma compared to eyes without glaucoma. Medical management is the preferred short-term mode of IOP control. Transscleral cyclophotocoagulation may be preferred over surgical intervention.     

Sex,gender, and retinoblastoma: analysis of 4351 patients from 153 countries

ObjectiveTo investigate in a large global sample of patients with retinoblastoma whether sex predilection exists for this childhood eye cancer.MethodsA cross-sectional analysis including 4351 treatment-naive retinoblastoma patients from 153 countries who presented to 278 treatment centers across the world in 2017. The sex ratio (male/female) in the sample was compared to the sex ratio at birth by means of a two-sided proportions test at global level, country economic grouping, continent, and for selected countries.ResultsFor the entire sample, the mean retinoblastoma sex ratio, 1.20, was higher than the weighted global sex ratio at birth, 1.07 (p < 0.001). Analysis at economic grouping, continent, and country-level demonstrated differences in the sex ratio in the sample compared to the ratio at birth in lower-middle-income countries (n = 1940), 1.23 vs. 1.07 (p = 0.019); Asia (n = 2276), 1.28 vs. 1.06 (p < 0.001); and India (n = 558), 1.52 vs. 1.11 (p = 0.008). Sensitivity analysis, excluding data from India, showed that differences remained significant for the remaining sample (χ² = 6.925, corrected p = 0.025) and for Asia (χ² = 5.084, corrected p = 0.036). Excluding data from Asia, differences for the remaining sample were nonsignificant (χ² = 2.205, p = 0.14).ConclusionsNo proof of sex predilection in retinoblastoma was found in the present study, which is estimated to include over half of new retinoblastoma patients worldwide in 2017. A high male to female ratio in Asian countries, India in specific, which may have had an impact on global-level analysis, is likely due to gender discrimination in access to care in these countries, rather than a biological difference between sexes.Subject terms: Eye cancer, Risk factors     

A short-term chick embryo in vivo xenograft model to study retinoblastoma cancer stem cells

Purpose:Cancer stem cells (CSCs) reported in various tumors play a crucial role in tumorigenesis and metastasis of retinoblastoma (Rb). Following the efforts to reduce, replace, and refine the use of mammalian models, we aimed to establish a short-term xenograft for Rb to evaluate the CSC properties of CD133^- Rb Y79 cells, using the well-established chick embryo chorioallantoic membrane (CE-CAM) assay.Methods:Y79 cells were cultured, labeled with two different dyes (CM-Dil Y79 and enhanced green fluorescent protein (eGFP)) and sorted for CD133^- and CD133 + subsets. Two million cells from each of the labeled groups were transplanted onto the abraded CAM on embryonic day 7 (E7). On E14, the tumor nodule formation on CAM and spontaneous metastasis to the embryos were evaluated by confocal microscopy, in vivo imaging, and histology.Results:Y79 cells formed pink–white raised perivascular nodules with feeder vessels on the CAM with both the types of labeled CD133^- cells. CD133^- cells, when compared to CD133 + cells, demonstrated significantly larger tumor volume (40.45 ± 7.744 mm³ vs 3.478 ± 0.69 mm³, P = 0.0014) and higher fluorescence intensity (CM-Dil: AUF = 6.37 × 10⁷ ± 7.7 × 10⁶ vs 1.08 × 10⁷ ± 1.6 × 10⁶; P < 0.0001; eGFP: AUF = 13.94 × 10⁴ ± 2.54 × 10⁴ vs AUF = 1.39 × 10⁴ ± 0.4 × 10⁴; P = 0.0003). The metastatic potential of CD133^- cells was also observed to be higher as noted by in vivo imaging and histopathology.Conclusion:This study highlights that CE-CAM is a feasible alternative nonmammalian model for evaluating tumorigenicity and metastatic potential of Y79 CSCs. Increased tumorigenicity and metastatic potential of CD133^- subset of tumor cells substantiate their CSC properties.     

Chirality, charge, and chain branching effects on dithiocarbamate-induced mobilization of cadmium from intracellular deposits in mice

The effects of three major structural features on the intracellular cadmium mobilizing potency of dithiocarbamates have been examined. These features, the chirality of the groups, the total ionic charge of the chelating agent, and the extent of chain branching, would be expected to affect the pharmacological properties of these chelating agents but to have little effect on the stability constants of the cadmium complexes involved. A total of 25 compounds (including 21 new ones) was prepared and used in animal studies designed to evaluate these effects. These included a series of amphipathic dithiocarbamates of the general type R1N(R2)CS2-Na+, where R1 is a relatively nonpolar organic group and R2 is derived from a reducing hexose. All of the factors examined influenced the potency of dithiocarbamates in the mobilization of cadmium from intracellular deposits. The compounds with R2 = galactose or mannose and R1 = benzyl were both more effective than the corresponding glucose derivatives in inducing the removal of cadmium from the liver and the whole body. Increases in the net negative charge of the chelating agent uniformly decreased the observed potency in the mobilization of hepatic and renal cadmium deposits. The replacement of a normal alkyl group by a branched-chain group of the same molecular weight also led to an increase in potency for the two pairs of compounds examined. Dithiocarbamates which are not amphipathic because of the presence of similar polar substituents for both R1 and R2, such as sodium diarabitylamine carbodithioate, were relatively ineffective as agents for the mobilization of intracellular cadmium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of wall shear stress in the aorta with the use of MR phase velocity mapping

MR phase velocity mapping was used to calculate wall shear stress (WSS) in the suprarenal and infrarenal abdominal aorta, two sites with very different proclivities for development of atherosclerosis. For the eight subjects studied, the average value of the mean (tune averaged over the cardiac cycle) WSS in the suprarenal aorta was 10.4 dynes/cm² at the posterior wall and 8.6 at the anterior wall. In the infrarenal aorta, WSS values were 4.7 at the posterior wall and 6.1 at the anterior wall. Peak WSS over the cardiac cycle was 48 and 54 at the anterior and posterior walls of the suprarenal aorta, respectively, and 33 and 30 at the anterior and posterior walls of the infrarenal aorta, respectively. Wide variation was found in both mean and peak WSS values among subjects. However, for 28 of 32 locations examined, mean and peak WSS were ingher in the suprarenal aorta than in the infrarenal aorta. Because atherosclerosis is more likely to form in the infrarenal aorta than in the suprarenal aorta, tins study supports the hypothesis that low WSS is a localizing factor for atherosclerosis, and ingh WSS may act as a deterrent against formation of atherosclerosis.