PTSD in women is associated with a block in conversion of progesterone to the GABAergic neurosteroids allopregnanolone and pregnanolone measured in plasma.

There is a need to identify new and more effective treatments for posttraumatic stress disorder (PTSD). Allopregnanolone and its stereoisomer pregnanolone (together termed ALLO) are metabolites of progesterone that positively and allosterically modulate GABA effects at GABAA receptors, thereby reducing anxiety and depression. Previous research revealed that women with PTSD had low cerebrospinal fluid (CSF) ALLO levels and a low ratio of ALLO to the allopregnanolone precursor 5α-DHP, consistent with deficient activity of the ALLO synthetic enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD). The current study examined ALLO and the ratio of ALLO to 5α-DHP in plasma at rest and in response to psychophysiological stressors in trauma-exposed, medication-free women with and without PTSD. Participants were examined twice in random order during the early follicular phase (eFP) and mid-luteal phase (mLP) of the menstrual cycle. Plasma neurosteroids were measured using gas chromatography-mass spectrometry. Results indicate that the ALLO to 5α-DHP ratio in plasma increases between the eFP and mLP. In addition, women with PTSD have a lower ratio of ALLO to 5α-DHP than trauma-exposed healthy women, as well as blunted increases in this ratio in response to a moderately stressful laboratory procedure, i.e., differential fear conditioning, across the menstrual cycle. Clinically feasible testing for 3α-HSD dysfunction is critical to translating this line of research into clinical care. Measurement of this ratio in plasma could facilitate patient stratification in clinical treatment trials, as well as precision medicine targeting of treatments that address ALLO synthesis deficits in women with PTSD.

Anterior segment ischemia: etiology, assessment, and management.

Anterior segment ischemia (ASI) is a potentially serious but rare complication of strabismus surgery. Among several risk factors, ASI occurs after strabismus surgery because of the nature of the anterior segment circulation. Disinsertion of rectus muscles leads to a decrease in the blood supply to the various anterior segment structures. We report a series of retrospective and prospective studies performed by our group focused on determining the risk of anterior segment ischemia following strabismus surgery, diagnosis, and modifications to surgical techniques to minimize the impact on anterior segment circulation. We found a significant decrease in postoperative anterior segment blood flow when operating vertical rectus muscles. Plication procedures preserve anterior segment circulation, and modifications to the technique allow the performance of adjustable sutures. Small adjustable selective procedures that spare the ciliary vessels have been demonstrated to be effective in patients with vertical and torsional diplopia. Ciliary sparing augmented adjustable transposition surgery decreases the risk of anterior segment ischemia while allowing management of potential post-operative alignment complications. Finally, ocular coherence tomography angiography is a valuable quantitative and qualitative technique to evaluate anterior segment ischemia. Strabismus surgeons should be aware of the risks of anterior segment ischemia when operating vertical rectus muscles. Modifications to standard surgical techniques allow surgeons to perform complex strabismus surgery in patients at risk for anterior segment ischemia.