An Association Between Large Optic Nerve Cupping and Cognitive Function

PurposeTo determine if a larger cup-to-disc ratio is associated with poor cognitive function in postmenopausal women without glaucoma or ocular hypertension.MethodsWe used data from the Women's Health Initiative (WHI) hormone trial, originally designed to test effects of hormone therapy (HT) on various health outcomes. Large cup-to-disc ratio was defined as greater than 0.6 in either eye based on stereoscopic optic nerve photographs. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) in the WHI Memory Study. Exclusions were no information on optic nerve grading; no 3MSE scores at the time of the eye examination, ocular hypertension (intraocular pressure >23 mm Hg, Goldmann applanation tonometry), or glaucoma medication use. A generalized linear model for log-transformed 3MSE scores was used for determining the association between large cup-to-disc ratio and 3MSE scores, adjusting for age, race, diabetes, body mass index, cardiovascular disease, smoking, HT randomization, education, and diabetic retinopathy.ResultsAnalyses included 1636 women (mean age ± standard deviation, 69.57 ± 3.64 years; 90.39% white). Of those, 122 women had large cup-to-disc ratio. The mean 3MSE scores in women with vs without large cup-to-disc ratio were 95.4 ± 6 vs 96.6 ± 5. In the adjusted model, women with large cup-to-disc ratio had statistically significantly lower 3MSE scores, compared with those without large cup-to-disc ratio, yielding the predicted mean difference in 3MSE scores of 0.75 with a standard error of 0.05 units (P = .04).ConclusionsPostmenopausal women who had large cup-to-disc ratio without glaucoma or ocular hypertension exhibited lower global cognitive function. Further investigation is warranted. NOTE: Publication of this article is sponsored by the American Ophthalmological Society

Association between cognitive function and large optic nerve cupping, accounting for cup-disc-ratio genetic risk score.

PurposeTo investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women.DesignThis was a retrospective study using data from the Women's Health Initiative.MethodsPatients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics.ResultsFinal analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007).ConclusionsIndependent of the CDR GRS, women with large CDR had a lower cognitive function

Association of macular pigment optical density with retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma

Objective To investigate associations between baseline macular pigment optical density (MPOD) and retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma (POAG) in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2).Methods and analysis MPOD was measured at CAREDS baseline (2001–2004) via heterochromatic flicker photometry (0.5° from foveal centre). Peripapillary retinal nerve fibre layer (RNFL), macular ganglion cell complex (GCC), ganglion cell layer (GCL), inner plexiform layer (IPL), and RNFL thicknesses were measured at CAREDS2 (2016–2019) via spectral-domain optical coherence tomography. Associations between MPOD and retinal thickness were assessed using multivariable linear regression.Results Among 742 eyes (379 participants), manifest POAG was identified in 50 eyes (32 participants). In eyes without manifest POAG, MPOD was positively associated with macular GCC, GCL and IPL thicknesses in the central subfield (P-trend ≤0.01), but not the inner or outer subfields. Among eyes with manifest POAG, MPOD was positively associated with macular GCC, GCL, IPL and RNFL in the central subfield (P-trend ≤0.03), but not the inner or outer subfields, and was positively associated with peripapillary RNFL thickness in the superior and temporal quadrants (P-trend≤0.006).Conclusion We observed a positive association between MPOD and central subfield GCC thickness 15 years later. MPOD was positively associated with peripapillary RNFL superior and temporal quadrant thicknesses among eyes with manifest POAG. Our results linking low MPOD to retinal layers that are structural indicators of early glaucoma provide further evidence that carotenoids may be protective against manifest POAG

Markers of Spontaneous Preterm Delivery in Women Living With HIV: Relationship With Protease Inhibitors and Vitamin D

Background: Women living with HIV (WLHIV) have increased risk of spontaneous preterm delivery (SPTD). We sought to identify plasma predictors of SPTD and their correlations with factors that increase the risk of SPTD, such as vitamin D deficiency and use of protease inhibitors. Design: Plasma was obtained from 103 WLHIV with SPTD (= 37 weeds) matched to cases 2:1 by race and gestational age at blood draw. TNF alpha, IFNy gamma, IL6, IL8, IL1 beta, IL18, IL17, granulocyte colony stimulating factor (GCSF), MCP1, IP10, sIL2Ra, sCD14, vascular endothelial factor a, monocyte colony stimulation factor, GRO alpha, MMP9, IL10, TGF beta, sCTLA4, and eicosanoids were compared between cases adjusting for known SPTD risk factors. Results: Participants had similar demographic characteristics, but cases had higher plasma HIV RNA, lower CD4 cells, and more advanced HIV disease compared with controls. High sIL2Ra was associated with increased risk of SPTD. High sCD14, GCSF, PGF2 alpha, and 5-HEPE were marginally associated with increased risk of SPTD. Women who initiated protease inhibitors-containing antiretroviral treatment before or during the first trimester had higher levels of GCSF and 5-HEPE compared with women without such exposure before plasma collection. Vitamin D insufficiency was associated with higher inflammatory sCD14 and PGF2 alpha, and lower anti-inflammatory 5-HEPE. Conclusions: The best plasma predictor of SPTD in WLHIV was sIL2R alpha, a marker of T-cell activation. Markers of monocyte activation and eicosanoids were marginally increased in WLHIV and SPTD, suggesting that they may also play a role in the pathogenesis of this disorder