Progression of diabetic retinopathy in women with pregestational diabetes during pregnancy and postpartum.

BACKGROUND: Diabetic retinopathy (DR) may worsen during pregnancy, but its course in the postpartum remains poorly understood. Understanding the natural history of DR during and after pregnancy can help determine when sight-threatening DR treatment should be administered. METHODS: A prospective longitudinal cohort study recruited pregnant women with pre-existing type 1 (T1D) or type 2 diabetes from two tertiary Diabetes Antenatal Clinics in Melbourne, Australia. Eye examination results in early pregnancy, late pregnancy, and up to 12-months postpartum were compared to determine DR changes. Two-field fundus photographs and optical coherence tomography scans were used to assess DR severity. RESULTS: Overall, 105 (61.4%) women had at least two eye examinations during the observation period. Mean age was 33.5 years (range 19-51); 54 women (51.4%) had T1D; 63% had HbA1c <7% in early pregnancy. DR progression rate was 23.8% (95% CI 16.4-32.6). Having T1D (RR 4.96, 95% CI 1.83-13.46), pre-existing DR in either eye (RR 4.54, 95% CI 2.39-8.61), and elevated systolic blood pressure (adjusted RR 2.49, 95% CI 1.10-5.66) were associated with increased risk of progression. Sight-threatening progression was observed in 9.5% of women. Among the 19 eyes with progression during pregnancy, 15 eyes remained stable, three eyes progressed, and only one eye regressed in the postpartum. CONCLUSIONS: Nearly 1 in 4 women had DR progression from conception through to 12-months postpartum; almost half of these developing sight-threatening disease. DR progression occurring during pregnancy was found to predominantly remain unchanged, or worsen, after delivery, with very few eyes spontaneously improving postpartum.

Prevalence of diabetic retinopathy in women with pregestational diabetes during pregnancy and the postpartum.

BACKGROUND: Diabetic retinopathy (DR) may be affected by pregnancy. The majority of prevalence data regarding DR in pregnancy predate the advent of contemporary guidelines for diabetes management during pregnancy. This study reports DR prevalence and associated risk factors in women with pregestational diabetes during pregnancy and the postpartum in Australia. METHODS: A total of 172 pregnant women with type 1 (T1DM) or type 2 diabetes diagnosed pre-pregnancy were prospectively recruited from two obstetrics hospitals in Melbourne (November 2017-March 2020). Eye examinations were scheduled in each trimester, at 3-, 6-, and 12-months postpartum. DR severity was graded from two-field fundus photographs by an independent grader utilising the Airlie House Classification. Sight-threatening DR (STDR) was defined as the presence of diabetic macular oedema or proliferative DR. RESULTS: Overall, 146 (84.9%) women had at least one eye examination during pregnancy. The mean age was 33.8 years (range 19-51), median diabetes duration was 7.0 years (IQR 3.0-17.0), 71 women (48.6%) had T1DM. DR and STDR prevalence during pregnancy per 100 eyes was 24.3 (95% CI 19.7-29.6) and 9.0 (95% CI 6.1-12.9); while prevalence in the postpartum was 22.2 (95% CI 16.5-29.3) and 10.0 (95% CI 5.4-17.9), respectively. T1DM, longer diabetes duration, higher HbA1c in early pregnancy, and pre-existing nephropathy were significant risk factors. CONCLUSIONS: The prevalence of DR in pregnant women was similar to the non-pregnant diabetic population in Australia. One in nine participants had STDR during pregnancy and the postpartum, highlighting the need to optimise DR management guidelines in pregnancy given the significant risk of vision loss.

Pregnancy and the eye.

PURPOSE OF REVIEW: The aim of this study was to summarize common eye changes that may occur during pregnancy, and how pregnancy may affect preexisting eye conditions such as glaucoma and diabetic retinopathy. Challenges and complexities surrounding the treatment of these eye conditions during pregnancy are also highlighted. RECENT FINDINGS: Refractive changes are common and may persist in the postpartum in patients with keratoconus. Although new medical and surgical glaucoma treatments are available, their safety in pregnancy is unknown. Limited use of topical and systemic glaucoma therapies is recommended, with a preference for selective laser trabeculoplasty as first line treatment in appropriate cases. The impact of pregnancy on diabetic retinopathy remains unclear. Although anti-vascular endothelial growth factor agents are first-line treatment for sight-threatening diabetic retinopathy, their effect on the developing foetus remains unknown and are therefore best avoided in the first and second trimesters. Noninfectious uveitis tends to become less active during pregnancy, allowing the potential tapering of systemic therapy and the use of local topical or injected corticosteroid treatment for active disease as required. SUMMARY: Significant changes can occur to the eye during pregnancy, wherein the optimal treatment for many ocular conditions remains uncertain, highlighting the need for further research to develop clear recommendations that best balance the need to preserve the mother's sight, and the health of the developing foetus. The need for preconception planning, and collaborative multidisciplinary care between the obstetrician, physician, ophthalmologist and paediatrician is paramount.

Epigenetic treatment-mediated modulation of PD-L1 predicts potential therapy resistance over response markers in myeloid malignancies: A molecular mechanism involving effectors of PD-L1 reverse signaling.

Recent evidence suggests an association exists between resistance to epigenetic therapy (EGT) and the expression of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) in myeloid malignancies. Biomarkers are required to predict resistance to EGT in myeloid malignancies, which together with the delineation of associated molecular mechanisms, may provide additional understanding for novel treatment strategies when investigating resistance to EGT. The present study aimed to investigate the in vivo effects of EGT on the expression of PD-1, PD-L1 and orphan nuclear receptor NUR77 with clinical responses in patients with myeloid malignancies. In addition, in vitro and in vivo characterization of the effects of EGT on the expression of NF-κB and Bcl-xL, potential downstream targets of PD-L1 reverse signaling, were evaluated to determine components of the molecular mechanism responsible for these effects. The in vivo effects of EGT on the expression of PD-1, PD-L1 and a previously identified molecular marker of response to EGT, NUR77 was characterized in peripheral blood mononuclear cells (PBMC) from patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with either azacytidine (Aza) alone or a combination of Aza and the histone deacetylase inhibitor (HDACi) LBH-589 during the first cycle of therapy. The correlation of clinical responses to treatment with EGT with the expression of PD-1, PD-L1 and NUR77 demonstrated that the induction of PD-L1 mRNA levels was associated with resistance to EGT despite the concurrent augmentation of NUR77 expression. The characterization of potential downstream effector molecules of reverse PD-L1 signaling identified EGT-mediated induction of Bcl-xL and NF-κB mRNA expression in vitro and in vivo, suggesting a potential anti-apoptotic molecular mechanism was responsible for PD-L1-mediated resistance to EGT. Taken together, these observations suggest that enhanced PD-L1 expression may confer resistance to EGT over known EGT response markers in myeloid malignancies, and provides a potential molecular mechanism involving the modulation of effectors of PD-L1 reverse signaling, which may in-part, be responsible for these effects.