Update on corneal collagen crosslinking for ectasia.

PURPOSE OF REVIEW: Corneal collagen crosslinking (CXL) is a minimally invasive treatment that can stabilize corneal ectatic disorders including keratoconus, pellucid marginal degeneration, or postrefractive surgery ectasia. The benefits of CXL have been well documented. New research is focused on modifying current treatment protocols with the goals of maximizing corneal stability while also shortening overall procedure time. RECENT FINDINGS: Accelerated CXL protocols have the goal of delivering the same ultraviolet A intensity as conventional protocols, but over a shorter time period. Accelerated protocols have shown success to date, but there are concerns for long-term corneal stability. Pulsed protocols may increase the long-term efficacy of the accelerated designs. In addition, transepithelial crosslinking protocols have been designed with the goal of reducing postoperative pain and lower the risk of infectious complications of epithelial-off conventional protocols. SUMMARY: Newer CXL protocols attempt to make the procedure safer and more effective. Current research is promising, but long-term studies are essential to understand how the new protocols may affect corneal stability.

Third Nerve Palsy as the Presenting Sign of Metastatic Endometrial Carcinoma with Lymphovascular Space Invasion.

We present a case of endometrial carcinoma (EC) presenting with a third cranial nerve palsy due to metastasis to the cavernous sinus. Although the tumour was only stage 1B, histopathologic features including higher grade and lymphovascular space invasion (LVSI) increase the risk of recurrent and metastatic disease. To our knowledge, this is the first case of EC presenting as a third cranial nerve palsy in the English-language ophthalmic literature. Clinicians should be aware that the risk of metastatic EC including neuro-ophthalmic presentations depends upon not only stage and grade but also the presence of unique histopathological findings such as LVSI.

Massive ischemic stroke as a complication of otitis media.

Cerebral artery infarction as a complication of acute otitis media is a rare complication. The mechanism appears to be the spread of meningeal inflammation to involve the walls of intracranial vessels, resulting in arterial thrombosis with ischemia or rupture with hemorrhage. We report the case of a 3 year old female with a history of global developmental delay who sustained a large left hemispheric stroke after middle cerebral artery infarction as a complication of an acute otitis media.

The SIRT1 activator SRT1720 reverses vascular endothelial dysfunction, excessive superoxide production, and inflammation with aging in mice.

Reductions in arterial SIRT1 expression and activity with aging are linked to vascular endothelial dysfunction. We tested the hypothesis that the specific SIRT1 activator SRT1720 improves endothelial function [endothelium-dependent dilation (EDD)] in old mice. Young (4-9 mo) and old (29-32 mo) male B6D2F1 mice treated with SRT1720 (100 mg/kg body wt) or vehicle for 4 wk were studied with a group of young controls. Compared with the young controls, aortic SIRT1 expression and activity were reduced (P < 0.05) and EDD was impaired (83 ± 2 vs. 96 ± 1%; P < 0.01) in old vehicle-treated animals. SRT1720 normalized SIRT1 expression/activity in old mice and restored EDD (95 ± 1%) by enhancing cyclooxygenase (COX)-2-mediated dilation and protein expression in the absence of changes in nitric oxide bioavailability. Aortic superoxide production and expression of NADPH oxidase 4 (NOX4) were increased in old vehicle mice (P < 0.05), and ex vivo administration of the superoxide scavenger TEMPOL restored EDD in that group. SRT1720 normalized aortic superoxide production in old mice, without altering NOX4 and abolished the improvement in EDD with TEMPOL, while selectively increasing aortic antioxidant enzymes. Aortic nuclear factor-κB (NF-κB) activity and tumor necrosis factor-α (TNF-α) were increased in old vehicle mice (P < 0.05), whereas SRT1720 normalized NF-κB activation and reduced TNF-α in old animals. SIRT1 activation with SRT1720 ameliorates vascular endothelial dysfunction with aging in mice by enhancing COX-2 signaling and reducing oxidative stress and inflammation. Specific activation of SIRT1 is a promising therapeutic strategy for age-related endothelial dysfunction in humans.

Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise.

We tested the hypothesis that peripheral blood mononuclear cells (PBMC) of older adults demonstrate a proinflammatory/-oxidative gene expression profile that can be improved by regular aerobic exercise. PBMC were isolated from young (n = 25, 18-33 yr) and middle-aged/older (n = 40, 50-76 yr) healthy adults. The older adults had greater mRNA expression (real-time RT-PCR) of the proinflammatory/-oxidant transcription factor nuclear factor-κB (1.58-fold, P < 0.05) and receptor for advanced glycation end products (1.12-fold, P < 0.05), the proinflammatory cytokines tumor necrosis factor-α (1.90-fold, P < 0.05) and monocyte chemoattractant protein-1 (1.47-fold, P < 0.05), and the oxidant-producing enzymes nicotinamide adenine dinucleotide phosphate-oxidase (0.91-fold, P < 0.05) and inducible nitric oxide synthase (2.60-fold, P < 0.05). In 11 subjects (58-70 yr), maximal oxygen consumption (+11%) and exercise time (+19%) were increased (both P < 0.001), and expression of the above proinflammatory/-oxidative genes was or tended to be decreased in PBMC after vs. before 2 mo of aerobic exercise (brisk walking ∼6 days/wk, 50 min/day, 70% of maximal heart rate). Expression of interleukin-6 was not different with age or exercise intervention. Age group- and exercise intervention-related differences in gene expression were independent of other factors. PBMC of healthy older adults demonstrate increased expression of several genes associated with inflammation and oxidative stress, which is largely ameliorated by habitual aerobic exercise. This proinflammatory/-oxidative gene signature may represent a therapeutic target for lifestyle and pharmacological prevention and treatment strategies.