A pathological indicator for dysthyroid optic neuropathy: tritan color vision deficiency.

PURPOSE: To investigate the sensitivity of the color vision test by Arden in patients with dysthyroid optic neuropathy (DON) to improve diagnosis. METHODS: In this observational, retrospective study, we included the medical records of 92 eyes (48 patients) with diagnosis of DON between 2008 and 2019 in order to evaluate the full spectrum of findings from the color vision test by Arden, and to determine potential importance of this test. Thirty-five patients were female, and 13 patients were male. The mean age was 58.0 years (range: 34-79) at the time of the DON diagnosis. RESULTS: Forty-one eyes displayed relatively good BCVA with ≤ 0.2 LogMAR. We found a protan value exceeding the threshold of ≥ 8% in 57 eyes (30 patients) at the time of the diagnosis. The sensitivity of protan was 61.9% (95% CI 51.2-71.8%), while that of tritan was a striking 98.9% (95% CI 94.1-99.9%). We discovered one pathological sign, tritan deficiency (based on a threshold of ≥ 8%) consistently in all eyes but one at the time of the diagnosis, regardless of the visual field defects or any changes in best-corrected visual acuity (BCVA). CONCLUSION: We found blue-yellow (tritan) deficiency, to be a sensitive and reliable indicator of dysthyroid optic neuropathy. We conclude that, in cases with suspected DON, a color vision test that can detect tritan deficiency is an essential tool for the adequate assessment, diagnosis, and treatment of DON.

Incidence of dyschromatopsy in glaucoma.

PURPOSE: As proven in studies dating back to the eighteenth century, color vision changes may occur early in the course of glaucoma. Our aim was to reevaluate the incidence of acquired color vision deficiency in glaucoma patients of the University hospital Zürich by using the Panel D-15 test. METHODS: Inclusion criteria of the study involved a diagnosis of glaucoma, age equal or greater than 18 years with no upper limit and a best-corrected visual acuity (BCVA) smaller than ≤ 0.7 logMAR. All volunteers were tested twice monocularly for color vision with (1) the Ishihara color plate test and (2) the Farnsworth and Lanthony Panel D-15 test by one examiner (L.B.). Using the Moment of Inertia Method of Vingrys and King-Smith (Investig Ophthalmol Vis Sci 29(1):50-63, 1988), we measured the color defect type (blue-yellow, red-green or non-selective). RESULTS: One hundred and fifty-one eyes of 87 glaucoma patients were included in this study. Nine eyes showed a deficient result in the Ishihara test, which proves a congenital red-green weakness. Fifty-one (33.8%) eyes showed color vision anomalies in the desaturated test and 24 (15.9%) eyes in the saturated Panel D-15 test. A total of 25.2% and 8.6% of eyes in the desaturated and saturated test were diffuse dyschromatopsia, respectively. The second most prevalent deficiencies were blue-yellow defects with 4.0% and 4.6% of saturated and desaturated results. Just the covariate visual acuity had a significant influence on the Panel D-15 result, whereas other variables like age, sex or intraocular pressure did not show any impact. CONCLUSION: This study ascertains that the long-known theory of color vision defects in patients with glaucoma is also relevant in our sample of 151 eyes, providing continuity to claims firstly reported many years ago. Despite our results highlighting more diffuse dyschromatopsia than other similar experiments, we have also proven that the tritanomalous defects occur more frequently than other color defects.

Estrogens and endocrine-disrupting chemicals differentially impact the bioenergetic fluxes of mammary epithelial cells in two- and three-dimensional models.

Due to its sensitivity to hormonal signaling, the mammary gland is often referred to as a sentinel organ for the study of endocrine-disrupting chemicals (EDCs), environmental pollutants that can interfere with the estrogen signaling pathway and induce mammary developmental defects. If and how EDCs impact mammary epithelial cell metabolism has not yet been documented. Herein, to study how estrogens and EDCs modulate mammary gland metabolism, we performed bioenergetic flux analyses using mouse mammary epithelial organoids compared to cells grown in monolayer culture. Several EDCs were tested, including bisphenol A (BPA), its close derivative BPS, a new BPA replacement copolyester called TritanTM, and the herbicide glyphosate. We report that estrogens reprogrammed mammary epithelial cell metabolism differently when grown in two- and three-dimensional models. Specific EDCs were also demonstrated to alter bioenergetic fluxes, thus identifying a new potential adverse effect of these molecules. Notably, organoids were more sensitive to low EDC concentrations, highlighting them as a key model for screening the impact of various environmental pollutants. Mechanistically, transcriptomic analyses revealed that EDCs interfered with the regulation of estrogen target genes and the expression of metabolic genes in organoids. Furthermore, co-treatment with the anti-estrogen fulvestrant blocked these metabolic impacts of EDCs, suggesting that, at least partially, they act through modulation of the estrogen receptor activity. Finally, we demonstrate that mammary organoids can be used for long-term studies on EDC exposure to study alterations in organogenesis/morphogenesis and that past pregnancies can modulate the sensitivity of mammary epithelial organoids to specific EDCs. Overall, this study demonstrates that estrogens and EDCs modulate mammary epithelial cell metabolism in monolayer and organoid cultures. A better understanding of the metabolic impacts of EDCs will allow a better appreciation of their adverse effects on mammary gland development and function.

Identifying missing pieces in color vision defects: a genome-wide association study in Silk Road populations.

Introduction: Color vision defects (CVDs) are conditions characterized by the alteration of normal trichromatic vision. CVDs can arise as the result of alterations in three genes (OPN1LW, OPN1MW, OPN1SW) or as a combination of genetic predisposition and environmental factors. To date, apart from Mendelian CVDs forms, nothing is known about multifactorial CVDs forms. Materials and Methods: Five hundred and twenty individuals from Silk Road isolated communities were genotyped and phenotypically characterized for CVDs using the Farnsworth D-15 color test. The CVDs traits Deutan-Protan (DP) and Tritan (TR) were analysed. Genome Wide Association Study for both traits was performed, and results were corrected with a False Discovery Rate linkage-based approach (FDR-p). Gene expression of final candidates was investigated using a published human eye dataset, and pathway analysis was performed. Results: Concerning DP, three genes: PIWIL4 (FDR-p: 9.01*10-9), MBD2 (FDR-p: 4.97*10-8) and NTN1 (FDR-p: 4.98*10-8), stood out as promising candidates. PIWIL4 is involved in the preservation of Retinal Pigmented Epithelium (RPE) homeostasis while MBD2 and NTN1 are both involved in visual signal transmission. With regards to TR, four genes: VPS54 (FDR-p: 4.09*10-9), IQGAP (FDR-p: 6,52*10-10), NMB (FDR-p: 8.34*10-11), and MC5R (FDR-p: 2.10*10-8), were considered promising candidates. VPS54 is reported to be associated with Retinitis pigmentosa; IQGAP1 is reported to regulate choroidal vascularization in Age-Related Macular Degeneration; NMB is involved in RPE homeostasis regulation; MC5R is reported to regulate lacrimal gland function. Discussion: Overall, these results provide novel insights regarding a complex phenotype (i.e., CVDs) in an underrepresented population such as Silk Road isolated communities.

Identification of non-volatile migrants from baby bottles by UPLC-Q-TOF-MS.

Baby bottles made of polypropylene, Tritan® and silicone were evaluated regarding the migration of non-volatile compounds using UPLC-QTOF-MS. Twenty-seven compounds were identified. In all polypropylene samples the migration of 2.2'-(tridecylimino)bis-ethanol and derivatives thereof were detected in concentrations below the specific migration limit (1.2 mg.kg-1). Furthermore, clarifying agents and glycerol derivatives were detected. Tritan baby bottle showed the migration of one slip additive. On the other hand, twenty compounds were detected in silicone baby bottles. Most of them were unknown compounds derived from acrylates. Once the migrants were identified, the risk assessment was carried out using the Threshold of Toxicological Concern (TTC) approach. The risk assessment of migrants coming from silicone samples showed levels above the threshold recommended as safe for babies.

Partial reversal of color vision impairment in type 2 diabetes associated with obstructive sleep apnea.

Objective: Tritan anomaly is a known acquired color defect seen in diabetic patients, with or without the evidence of clinical signs of diabetic retinopathy (DR). We report a case of a 45-year-old diabetic patient with tritan pattern color defect associated with obstructive sleep apnea and its partial reversal with continuous positive airway pressure (CPAP) ventilation. Methods: A 45-year-old male with diabetes, wildlife photographer by profession, presented with specific complaints of seeing all objects in the surrounding with a greenish tinge in both the eyes. He underwent a comprehensive eye examination including Farnsworth-Munsel 100 (FM 100) hue test, multifocal electroretinogram, microperimetry, spectral domain optical coherence tomography (SDOCT), and arterial oxygen saturation. Results: The subject was found to have a low arterial oxygen saturation (PaO2) of 86%. He was then advised inhalation of 100% oxygen for 15 min, following which he reported improvement in his visual symptoms. FM 100, OCT, and microperimetry were repeated after oxygenation. He was referred to a specialty hospital for further evaluation of the cause for reduced blood oxygen saturation and was further advised for sleep study, where he was diagnosed to have obstructive sleep apnea (OSA) with an apnea-hypopnea index of 20.9. Conclusion: The subject was advised weight loss measures and oral application of continuous positive airway pressure. Since then, he is under our regular follow-up and has never experienced or complained of any color vision problems. This case report highlights the presence of associated systemic disorders like obstructive sleep apnea in individuals with diabetes that can present with color vision problems.

A robotic BG1Luc reporter assay to detect estrogen receptor agonists.

Endocrine disrupting chemicals with estrogenic activity (EA) have been associated with various adverse health effects. US agencies (ICCVAM/NICEATM) tasked to assess in vitro transcription activation assays to detect estrogenic receptor (ER) agonists for EA have recently validated a BG1Luc assay in manual format, but prefer robotic formats. We have developed a robotic BG1Luc EA assay to detect EA that demonstrated 100% concordance with ICCVAM meta-analyses and ICCVAM BG1Luc results in manual format for 27 ICCVAM test substances, i.e. no false negatives or false positives. This robotic assay also consistently assessed other, more problematic ICCVAM test substances such as clomiphene citrate, L-thyroxin, and tamoxifen. Agonist responses using this robotic BG1Luc assay were consistently inhibited by the ER antagonist ICI 182,780, confirming that agonist responses were due to binding to ERs rather than to a non-specific agonist response. This robotic assay also detected EA in complex mixtures of substances such as extracts of personal care products, plastic resins or plastic consumer products. This robotic BG1Luc assay had at least as high accuracy and greater sensitivity and repeatability when compared to its manual version or to the other ICCVAM/OECD validated assays for EA (manual BG1Luc and CERI).

Prevalence of color-vision deficiency among male high-school students

@#Objective This study determined the prevalence of color-vision deficiency among male high-school students in a public school. Methods Male high-school students were screened for color-vision deficiency using 6 plates of the Ishihara pseudoisochromatic plates. All students with one or more errors were reexamined at a later date with the full 15 Ishihara plates and the Farnsworth D15 (FD15) test. A detailed history was taken and an ocular examination was conducted. Students who identified less than 10 plates correctly on the FD15 were classified as color-deficient and underwent the Farnsworth Munsell 100 hue (FM 100) test. The results were statistically analyzed. Results A total of 1,258 male high-school students, aged 12 to 16 years, were included in the study, 122 of whom failed the screening test. Of these, 106 completed the 15 Ishihara plates. Sixty-five failed and were classified as color-visiondeficient, of which 64 (98%) were deutans. Deutan was also the most common deficiency determined using the FD15 (78.95%) and FM100 (44.19 %) hue tests. Conclusion The prevalence of color-vision deficiency among male students in a public high school was 5.17% (65/1,258). The most common deficiency was the deutan type.