The shrinking eye: dimensional changes in the young child's eye after glaucoma drainage device implantation for refractory childhood glaucoma.

PURPOSE: To investigate the magnitude of reduction in the axial length (AL) and corneal diameter following glaucoma drainage device (GDD) placement and intraocular pressure (IOP) reduction in glaucoma patients <3 years of age at surgery. METHOD: The medical records of consecutive childhood glaucoma patients who underwent GDD implantation at a single practice between 2013 and 2018 and were <3 years of age at surgery were reviewed retrospectively. Demographics, glaucoma diagnoses, surgical details, and pre- and post-procedure measurements of AL, IOP, corneal diameter, central corneal thickness, presence of corneal edema, and cup:disk ratio were analyzed. RESULTS: A total of 16 eyes of 10 patients were included. Before GDD placement, mean AL was 23.49 ± 3.05 mm. Mean AL reduction after placement was 0.80 ± 0.85 mm (P = 0.001); median AL reduction, 0.93 mm (range, -3.05 to +0.59). Mean IOP reduction after GDD placement was 15.0 ± 6.0 mm Hg (P < 0.0001). IOP reduction and AL reduction were significantly related (P = 0.0013). Mean corneal diameter before GDD placement was 13.0 ± 1.6 mm; mean corneal diameter reduction after placement was 0.3 ± 0.3 mm (P = 0.012). Reduction of corneal diameter and of AL were significantly related (P = 0.03); corneal diameter and IOP were not (P = 0.40). Objective cupping reversal after GDD was noted in 50% of eyes with documented cup:disk ratio. CONCLUSIONS: In this study cohort, reduction in AL, corneal diameter, and cup:disk ratio was found to be correlated with reduced IOP after GDD placement. This result merits consideration during surgical planning for glaucoma patients <3 years of age.

Septic Cerebral Venosinus Thrombosis Secondary to an Odontogenic Infection.

BACKGROUND: Cerebral venosinus thrombosis (CVT); is an uncommon, potentially fatal disease that is more common in young adults and children. Thrombophilia, elevated estrogenic states, and infections are the most common risk factors in patients who develop CVT. CASE: A 69-year-old man with a right-sided odontogenic infection presented with fever, headache, opthalmoplegia, and periorbital swelling. Imaging revealed evidence of meningitis and thrombosis of bilateral ophthalmic veins, the cavernous sinus, right internal jugular vein, and sigmoid sinus. The patient was treated with empiric antibiotic therapy and unfractionated heparin. He recovered with only mild impairment in right eye abduction. DISCUSSION: Early diagnosis and prompt treatment of CVT is vital in reducing the associated morbidity and mortality. Unfractionated or low molecular weight heparin may be safely used in CVT patients. Thrombolytic therapy is an option in clinically severe cases. Treatment also includes addressing the underlying cause and management of early complications.

Getting Hooked: A Simple Technique for the Treatment of Adhesive Injuries to the Eyelids.

BACKGROUND: Ocular chemical injuries due to accidental exposure or application of cyanoacrylate, commonly known as "superglue," have increased over the past 30 years. However, current treatment options to relieve eyelid adhesions due to cyanoacrylate applications are difficult to successfully execute and can require sedation or general anesthesia. Here we describe a simple technique to release eyelid adhesions due to cyanoacrylate, or other adhesive agents, that can be successfully performed at bedside without sedation. DISCUSSION: Topical anesthetic is instilled in the involved eye through an opening identified in the lid fissure. A Jameson muscle hook is inserted through the opening with the distal element of the hook normal to the surface of the eye. The hook is then pulled parallel to the lid margins and through the site of adhesion while counter pressure is applied with the fellow hand in the opposite motion of the hook. Residual glue from the eyelashes can be trimmed with blunt-tip scissors. Examination of the eyelids and ocular surface after application of the technique to open the eyelids showed successful release of adhesion sites with no additional injuries to the eye itself. CONCLUSIONS: A Jameson muscle hook can be used in emergency departments to safely and successfully relieve eyelid adhesions due to the inadvertent application of cyanoacrylate glue without the use of general anesthesia.

Genome-wide impact of the BRG1 SWI/SNF chromatin remodeler on the transforming growth factor beta transcriptional program.

The transcription factors Smad2 and Smad3 mediate a large set of gene responses induced by the cytokine transforming growth factor beta (TGFbeta), but the extent to which their function depends on chromatin remodeling remains to be defined. We observed interactions between these two Smads and BRG1, BAF250b, BAF170, and BAF155, which are core components of the SWI/SNF chromatin-remodeling complex. Smad2 and Smad3 have similar affinity for these components in vitro, and their interactions are primarily mediated by BRG1. In vivo, however, BRG1 predominantly interacts with Smad3, and this interaction is enhanced by TGFbeta stimulation. Our results suggest that BRG1 is incorporated into transcriptional complexes that are formed by activated Smads in the nucleus, on target promoters. Using BRG1-deficient cell systems, we defined the BRG1 dependence of the TGFbeta transcriptional program genome-wide. Most TGFbeta gene responses in human epithelial cells are dependent on BRG1 function. Remarkably, BRG1 is not required for the TGFbeta-mediated induction of SMAD7 and SNON, which encode key mediators of negative feedback in this pathway. Our results provide a genome-wide scope of the participation of BRG1 in TGFbeta action and suggest a widespread yet differential involvement of BRG1 SWI/SNF remodeler in the transcriptional response of many genes to this cytokine.

Cyclin-dependent kinase inhibitors uncouple cell cycle progression from mitochondrial apoptotic functions in DNA-damaged cancer cells.

DNA damage results in transcriptional induction of p53 target genes, including the cyclin-dependent kinase (CDK) inhibitor p21(Cip1) (CDKN1A) and the proapoptotic Bcl-2 family member p53 up-regulated modulator of apoptosis (PUMA). Depending on the cellular context, p21(Cip1) and PUMA mediate cell cycle arrest and apoptosis, respectively. By imposing cell cycle arrest at the expense of apoptosis, p21(Cip1) can sharply reduce the effectiveness of DNA-damaging anticancer agents in colorectal cancer cells. We investigated the link between cell cycle progression and the onset of apoptosis in DNA-damaged cells by analyzing the activation of the apoptotic cascade in p21(Cip1)-deficient HCT116 colorectal cancer cells. DNA damage induced a similar level of p53 activation and PUMA induction in p21(Cip1)-deficient cells compared with wild-type isogenic counterparts. p21(Cip1) did not act as a direct blocker of PUMA. However, only p21(Cip1)-deficient cells showed extensive cytochrome c release, mitochondrial membrane depolarization, and caspase activation. An increase in caspase activation occurred as these cells reached M-phase and incurred polyploidy. When ectopically expressed in p21(Cip1)-deficient HCT116 cells, p21(Cip1), its family member p27(Kip1), and the structurally unrelated CDK inhibitor p16(Ink4a) were similarly effective at causing cell cycle arrest and inhibiting DNA damage-induced apoptotic events such as cytochrome c release, mitochondrial membrane depolarization, and activation of the caspase cascade. These observations suggest that by blocking dysregulated cell cycle progression, CDK inhibitors can influence the sensitivity of the mitochondria to proapoptotic signals in DNA damage-induced cancer cells.

Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation.

FoxO Forkhead transcription factors are shown here to act as signal transducers at the confluence of Smad, PI3K, and FoxG1 pathways. Smad proteins activated by TGF-beta form a complex with FoxO proteins to turn on the growth inhibitory gene p21Cip1. This process is negatively controlled by the PI3K pathway, a known inhibitor of FoxO localization in the nucleus, and by the telencephalic development factor FoxG1, which we show binds to FoxO-Smad complexes and blocks p21Cip1 expression. We suggest that the activity of this network confers resistance to TGF-beta-mediated cytostasis during the development of the telencephalic neuroepithelium and in glioblastoma brain tumor cells.

Myc suppression of the p21(Cip1) Cdk inhibitor influences the outcome of the p53 response to DNA damage.

Activation of the tumour suppressor p53 by DNA damage induces either cell cycle arrest or apoptotic cell death. The cytostatic effect of p53 is mediated by transcriptional activation of the cyclin-dependent kinase (CDK) inhibitor p21(Cip1), whereas the apoptotic effect is mediated by transcriptional activation of mediators including PUMA and PIG3 (ref. 2). What determines the choice between cytostasis and apoptosis is not clear. Here we show that the transcription factor Myc is a principal determinant of this choice. Myc is directly recruited to the p21(Cip1) promoter by the DNA-binding protein Miz-1. This interaction blocks p21(Cip1) induction by p53 and other activators. As a result Myc switches, from cytostatic to apoptotic, the p53-dependent response of colon cancer cells to DNA damage. Myc does not modify the ability of p53 to bind to the p21(Cip1) or PUMA promoters, but selectively inhibits bound p53 from activating p21(Cip1) transcription. By inhibiting p21(Cip1) expression Myc favours the initiation of apoptosis, thereby influencing the outcome of a p53 response in favour of cell death.