A novel therapeutic hypothesis for craniosynostosis syndromes: Clover to clever.

Cloverleaf skull is a complex skull deformity named after its cloverleaf shape. The primary pathogenic factor is craniosynostosis. Craniosynostosis could result in limited development of skull, brain, maxillofacial and nervous system, thus arising a series of complex syndromes, including Crouzon, Apert, Pfeiffer, Saethre-Chotzen and Muenke syndromes. Craniosynostosis syndromes exhibit a group of similar symptoms because of the mutual cause, craniosynostosis, with Crouzon syndrome being the most common one. At present, the surgical approach for Craniosynostosis syndromes has been established and generally accepted, including a series of surgical interventions in stages according to patients' age, severity and function of skull malformation. It's a large, complex, long time span deformity correcting procedure with formidable limitations, including high risk, expensive cost, quantity shortage of qualified surgeons and unsatisfactory successful rate for complicated cases. Hence, a new nonsurgical therapy for patients with craniosynostosis syndromes is seriously needed. A concept of Dynamic Cranial Suture Management (DCSM) was introduced. It includes objective and evaluable monitoring tools and craniosynostosis patent modifying drugs or medications tools which consist of regulatory factors for osteoclasts, osteoblasts and mesenchymal stem cells. By using these tools alternatively in different skull developing stages, DCSM is designed to prevent craniosynostosis. A Crouzon syndrome case was also presented.

Endogenous Endophthalmitis Caused by Klebsiella pneumoniae: A Ten-Year Retrospective Study in Western China.

OBJECTIVES: The aim of this study was to analyse the clinical features, microbiology results, management and outcomes of patients with endogenous endophthalmitis caused by Klebsiella pneumoniae in western China. METHODS: A retrospective review of medical records of 10 eyes in 10 subjects diagnosed with endogenous K. pneumoniae endophthalmitis from January 2008 to December 2018 was undertaken. RESULTS: The top 3 predisposing medical conditions included diabetes mellitus (50%), malignancy (20%) and cardiac stent implantation (10%). Extraocular infective foci were mainly found in the liver (40%), lungs (20%) and kidneys (10%). The positive culture rate was 85.71% (6/7) in vitreous samples, 83.33% (5/6) in blood samples and 100% (4/4) in body fluid samples. Only 20% of the patients, who had good initial visual acuity (VA) better than hand movement (HM), achieved a final VA better than 1.0 (log MAR). The mortality rate was 10%. CONCLUSIONS: Though the prognosis of endogenous K. pneumoniae endophthalmitis is often poor, patients with an initial VA better than HM may have a good prognosis under comprehensive treatments, including vitrectomy, systemic sensitive antibiotic injection and drainage of the primary infection loci.

A new strategy to interpret OCT posterior pole asymmetry analysis for glaucoma diagnosis.

AIM: To detect early glaucoma by optical coherence tomography (OCT) posterior pole asymmetry analysis. METHODS: Totally 39 eyes from 39 healthy subjects, 40 eyes from 40 mild glaucoma patients, 33 eyes from 33 moderate glaucoma patients and 41 eyes from severe glaucoma patients were included in this study. All subjects underwent posterior pole asymmetry analysis (PPAA) of OCT and the posterior pole area was divided into three zones. Means, standard deviations and 95% confidence intervals of each zone asymmetry in control group were assessed. Retina thickness asymmetry (RTA) of different stage of glaucoma were compared for each zone, and receiver operating characteristic (ROC) curves were made to test the efficacy of strategies using different zones to discriminate glaucomatous eyes from the healthy ones. RESULTS: In a healthy population, RTA of the centre zone showed the minimal mean value (3.085 µm), standard deviation (1.756), and the narrowest 95% confidence interval (from 2.360 to 3.810 µm). It was only in the center zone that RTA exhibited significant difference between control and moderate glaucoma group (P<0.01), as well as control and severe glaucoma group (P<0.00001). The strategy utilized in the center zone had the strongest diagnostic capability (zone 3 AUROC=0.816, P=0.0016) in comparison to that of the periphery area (zone 1 AUROC=0.675, P=0.0016; zone 2 AUROC=0.623, P=0.0197), the whole posterior pole involved interpreting strategy showed inferior diagnostic power than the centre zone dependent strategy (z=2.851, P=0.0044). CONCLUSION: Utilizing the posterior pole centre zone to interpret OCT PPAA results are more effective than making use of the whole posterior pole map.

ipRGCs: possible causation accounts for the higher prevalence of sleep disorders in glaucoma patients.

Sleep accounts for a third of one's lifetime, partial or complete deprivation of sleep could elicit sever disorders of body function. Previous studies have reported the higher prevalence of sleep disorders in glaucoma patients, but the definite mechanism for this phenomenon is unknown. On the other hand, it is well known by us that the intrinsically photosensitive retinal ganglion cells (ipRGCs) serve additional ocular functions, called non-image-forming (NIF) functions, in the regulation of circadian rhythm, melatonin secretion, sleep, mood and others. Specifically, ipRGCs can directly or indirectly innervate the central areas such as suprachiasmatic nucleus (SCN), downstream pineal gland (the origin of melatonin), sleep and wake-inducing centers and mood regulation areas, making NIF functions of ipRGCs relate to sleep. The more interesting thing is that previous research showed glaucoma not only affected visual functions such as the degeneration of classical retinal ganglion cells (RGCs), but also affected ipRGCs. Therefore, we hypothesize that higher prevalence of sleep disorders in glaucoma patients maybe result from the underlying glaucomatous injuries of ipRGCs leading to the abnormalities of diverse NIF functions corresponding to sleep.

ß-III-Tubulin: a reliable marker for retinal ganglion cell labeling in experimental models of glaucoma.

AIM: To evaluate the reliability of ß-III-Tubulin protein as a retinal ganglion cell (RGC) marker in the experimental glaucoma model. METHODS: Glaucoma mouse models were established by injecting polystyrene microbeads into the anterior chamber of C57BL/6J mice, then their retinas were obtained 14d and 28d after the intraocular pressure (IOP) was elevated. Retinal flat mounts and sections were double-labeled by fluorogold (FG) and ß-III-Tubulin antibody or single-labeled by ß-III-Tubulin antibody, then RGCs were counted and compared respectively. RESULTS: IOP of the injected eyes were elevated significantly and reached the peak at 22.8±0.7 mm Hg by day 14 after injection, then dropped to 11.3±0.7 mm Hg by day 28. RGC numbers counted by FG labeling and ß-III-Tubulin antibody labeling were 64 807±4930 and 64614±5054 respectively in the control group, with no significant difference. By day 14, RGCs in the experimental group decreased significantly compared to the control group, but there was no significant difference between the FG labeling counting and the ß-III-Tubulin antibody labeling counting either in the experimental group or in the control group. The result was similar by day 28, with further RGC loss. CONCLUSION: Our result suggested that the ß-III-Tubulin protein was not affected by IOP elevation and can be used as a reliable marker for RGC in experimental models of glaucoma.