Glaucoma

New glaucoma treatments: Canaloplasty Canaloplasty (pronounced Kah-NAL-oh-plas-tee) is an advanced minimally invasive glaucoma treatment. As glaucoma can cause a permanent loss of vision, this procedure can provide patients with glaucoma a peace of mind not possible with use of glaucoma drops alone. Canaloplasty can reduce eye pressure by nearly 40%, and most glaucoma patients who have had Canaloplasty can cut their glaucoma drops in half. In some cases, Canaloplasty can even eliminate the need for Glaucoma drops. Canaloplasty can be done on its own or at the same time as cataract surgery (in which case it is called PhacoCanaloplasty). It is a non-penetrating glaucoma surgery which means it does not require creation of a hole in the eye (fistula) nor does it result in a bleb as required with the more traditional glaucoma surgery called trabeculectomy (trab for short). How it is perform? Canaloplasty uses a micro-catheter to open the eyes natural drainage system (Schlemms canal). This canal is then opened using a sterile, gel-like material (viscoelastic). The iTrack micro-catheter is then removed while a suture is threaded through Schlemms canal. The suture is then tied down resulting in tension on the the inner wall of the canal just as you might pull on the strings of a hoodie to close the hood over your face. The suture placed in the eyes drainage canal can keep the canal stretched open for years. Once this canal is opened, the eyes fluid can exit through a more natural process allowing the pressure in the eye to drop to a more normal level. http://new-glaucoma-treatments.com/canaloplasty/

Gene therapy for glaucoma: Glaucoma is a chronic progressive disease for which ideal treatment would provide a localized long-lasting therapy with minimal side-effects. A gene therapy approach in which a mutated gene is replaced or inactivated, or in which a new gene is introduced, could provide a novel and more effective way of targeting the disease. Both viral and nonviral vector gene delivery systems have been used to target specific tissues involved in the pathogenesis of glaucoma. These tissues include the trabecular meshwork, ciliary body, ciliary epithelium, Mller cells, and retinal ganglion cells. Recent studies in large animal models have demonstrated effective longterm gene expression in the trabecular meshwork following intracameral delivery of adenoassociated viral vectors and lentiviral vectors with limited effect on surrounding ocular tissues. Other promising studies have focused on vector-mediated expression of neurotrophic factors and have demonstrated a neuroprotective effect following intravitreal delivery of vectors in glaucomatous animal models. Gene therapy techniques to lower intraocular pressure and to

provide neuroprotection, and the continued development of tissue-specific vectors, it seems that we are well poised for a new generation of treatments for glaucoma. Stem cell injection 'reverses glaucoma' People with glaucoma could receive a simple injection in the near future to halt - or even reverse - the eye condition.Scientists at Cambridge University believe the technique, which uses stem cells, could even cure blindness one day. They have already had success in rats and hope to start trials in humans within five years. The method involves taking stem cells from bone marrow and injecting them in a solution into the back of the eye. There, they help existing optic nerve cells from degenerating further. They can also transform themselves into new optic nerve cells, reversing damage and improving eyesight. Acoording to Professor Keith Martin, a neuroscientist at Cambridge University and an eye surgeon at Addenbrooke's Hospital, "Finding treatments to reverse blindness is no longer in the realm of science fiction. "We are doing it in animal models and results are so encouraging that we hope to move forward to testing on humans soon."Stem cell treatment is moving forward very fast in many branches of the medicine and we are seeing some of the best results in eyes." He added: "We have concentrated on glaucoma because it is so common, but there are quite a few diseases that affect the optic nerve, such as inflammatory diseases, so it could be used here too." While the team has had success in halting glaucoma in rats and reversing its decline to some extent, they are still working on the ultimate objective - how to cure blindness. http://www.telegraph.co.uk/health/healthnews/8376433/Stem-cell-injection-reversesglaucoma.html

Use of fixed-dose combination drugs for the treatment of glaucoma: Glaucoma is a leading cause of irreversible visual loss. This potentially blinding disease is a progressive optic neuropathy associated with elevated intraocular pressure (IOP). Initial therapy for glaucoma typically consists of topical medications or laser treatment to lower IOP. Frequently, more than one medication is required to achieve adequate control of IOP. However, more medications means more bottles and greater complexity for the patient. There are several potential benefits of fixed combination medications compared with using the individual components separately. These include a reduction in the total number of drops and preservative instilled per day, cost savings, improved tolerability and compliance and avoiding the washout effect resulting from rapid-sequence instillation of multiple drops. Attempts to develop effective fixed combinations of glaucoma medications date back several decades. In recent years, fixed combinations of commonly paired drugs have been approved by various regulatory bodies in different countries and have gained wide acceptance. Current commercially available, fixed combination drugs include the topical beta-adrenoceptor antagonist timolol 0.5% combined with a prostaglandin, a topical carbonic anhydrase inhibitor or an alpha-adrenoceptor agonist. Although there is no uniformity among registration trial designs, most published literature compares the efficacy of the fixed combination to the individual components and to concomitant use of both components. Various factors inherent to study design such as medication run-in, washout periods and peak and trough effects have to be taken into consideration when

analysing the demonstrated efficacy of fixed combinations. Fixed combination treatments offer effective IOP control while reducing the washout effect and exposure to preservatives. They are also convenient. However, fixed combinations also remove the possibility of titrating the individual components both in terms of concentration and timing of administration. In addition, fixed combinations might not always provide the same efficacy as proper use of the individual components. The clinician must make individualised assessments when weighing the convenience of these medications against their limitations for specific patients.when analysing the demonstrated efficacy of fixed combinations. Fixed combination treatments offer effective IOP control while reducing the washout effect and exposure to preservatives. They are also convenient. However, fixed combinations also remove the possibility of titrating the individual components both in terms of concentration and timing of administration. In addition, fixed combinations might not always provide the same efficacy as proper use of the individual components. The clinician must make individualised assessments when weighing the convenience of these medications against their limitations for specific patients.

multiple sclerosis Mitochondrial changes within axons in multiple sclerosis: an update. There is a gathering body of evidence implicating an energy-deficient state in the pathogenesis of MS, and mitochondrial defects have been the subject of a number of previous reviews. In myelinated axons within the central nervous system, over 90% of mitochondria are located within juxtaparanodal and internodal axoplasm. The electrogenic machinery, mitochondria and myelin form a triad that is disrupted in MS. The axonal mitochondrial content increases following demyelination and persists despite the residual inflammatory reaction subsiding to levels seen in control cases. The changes in axonal mitochondrial content following demyelination in MS and experimental demyelination in vivo and in vitro do not return to the levels in nondemyelinated and myelinated axons following remyelination.Understanding the mechanisms of axonal mitochondrial response to a disturbance in myelin and determining if certain aspects of the axonal mitochondrial response to demyelinated and remyelinated axons are beneficial may identify potential therapeutic targets for the progressive forms of MS. http://www.ncbi.nlm.nih.gov/pubmed/22543429

Mitoxantrone: a review of its use in multiple sclerosis. Mitoxantrone (Novantrone), a synthetic anthracenedione derivative, is an antineoplastic, immunomodulatory agent. Its presumed mechanism of action in patients with multiple sclerosis (MS) is via immunomodulatory mechanisms, although these remain to be fully elucidated. Intravenous mitoxantrone treatment improved neurological disability and delayed progression of MS in patients with worsening relapsing-remitting (RR) [also termed progressiverelapsing (PR) MS] or secondary-progressive (SP) disease. In a pivotal randomised, doubleblind, multicentre trial, mitoxantrone 12 mg/m(2) administered once every 3 months for 2 years provided significant improvements in neurological disability ratings, including Kurtzke Expanded Disability Status Scale (EDSS), Ambulatory Index (AI) and Standardised Neurological Status (SNS) scores, compared with placebo. The drug also significantly reduced the mean number of corticosteroid-treated relapses and prolonged the time to the first treated relapse, with the beneficial effects on disease progression supported by magnetic resonance imaging. Mitoxantrone treatment may be sustained for at least 12 months after cessation of treatment, mean changes from baseline at 36 months in EDSS, AI and SNS scores of 0.10, 0.61 and 0.19, Concomitant intravenous mitoxantrone 20mg plus intravenous methylprednisolone 1g once every month for 6 months was more effective than intravenous methylprednisolone monotherapy in preventing the development of new gadolinium-enhanced lesions in patients with very active RRMS or SPMS. The drug was generally well tolerated in patients with MS. Adverse events were generally mild to moderate in severity and usually resolved upon discontinuation of treatment or with appropriate pharmacotherapy.

What is new in the treatment of multiple sclerosis? Weinstock-Guttman B, Jacobs LD. Multiple sclerosis (MS) is considered an autoimmune disease associated with immune activity directed against central nervous system antigens. Based on this concept, immunosuppression and immunomodualtion have been the mainstays of therapeutic strategies in MS. During the last decade new therapies have been shown to significantly improve MS disease course. The effective therapies have led to a better understanding of MS pathogenesis and further development of even more efficient therapeutic interventions. Recombinant interferon (IFN)beta represents the first breakthrough in MS therapy. Three large placebo-controlled, double-blind studies and several smaller studies have demonstrated the efficacy of different forms of IFNbeta administrated by either subcutaneous or intramuscular routes and at different doses in patients with active relapsing-remitting multiple sclerosis (RR-MS). The three IFNbeta drugs are IFNbeta-1b and two IFNbeta-1a preparations (Avonex and Rebif). Although each clinical trial had unique features and differences that make direct comparisons difficult, the aggregate results demonstrate a clear benefit of IFNbeta for decreasing relapses and probability of sustained clinical disability progression in patients with RR-MS. All forms of IFNbeta therapy had beneficial effects on the disease process measured by brain magnetic resonance imaging (MRI). IFNbeta-1a (Avonex) also showed benefit in slowing or preventing the development of MS related brain atrophy measured by MRI after 2 years of therapy. Glatiramer acetate, the acetate salt of a mixture synthetic polypeptides thought to mimic the myelin basic protein showed a significant positive results in reducing the relapse rate in patients with RR-MS. Follow up of these patients for approximately 3 years continued to show a beneficial effect on disease relapse rate. Recent MRI data supported the beneficial clinical results seen with glatiramer acetate in patients with RR-MS. Recent studies using intravenous immune globulin (IVIG) suggest that IVIG could be effective to some degree in patients with RR-MS. However, there is not enough evidence that IVIG is equivalent to IFNbeta or glatiramer acetate in the treatment of patients with RR-MS.

Intravenous immunoglobulin for Guillain-Barr syndrome. The efficacy of intravenous immunoglobulin for treating Guillain-Barr syndrome. Another Cochrane systematic review has shown that plasma exchange significantly hastens recovery. We found six randomised trials comparing intravenous immunoglobulin with plasma exchange. We undertook a meta-analysis of five trials involving 536, mostly adult participants who were unable to walk unaided and had been ill for less than two weeks. Our primary outcome measure was the change in a seven-grade disability scale four weeks after randomisation. The weighted mean difference of this measure was not statistically significant, being only -0.02 (95% confidence interval -0.25 to 0.20) of a disability grade more improvement in the intravenous immunoglobulin than the plasma exchange group. There were no statistically significant differences in other measures. One trial involving 249 participants compared plasma exchange followed by intravenous immunoglobulin with plasma exchange alone. Another involving 37 participants compared immunoabsorption followed by intravenous immunoglobulin with immunoabsorption alone. Neither revealed significant extra benefit from intravenous immunoglobulin. One study with 39 participants showed a trend towards more improvement with high-dose compared with low-dose intravenous immunoglobulin. Another trial with 51 children found no significant difference in outcome when the standard dose was given over two days rather than five days. Three studies including a total of 75 participants suggested that in children intravenous immunoglobulin significantly hastens recovery compared with supportive care. In adults, there are no adequate comparisons with placebo. Randomised trials in severe disease show that intravenous immunoglobulin started within two weeks from onset hastens recovery as much as plasma exchange, which is known to be more effective than supportive care. Treatment with intravenous immunoglobulin is significantly more likely to be completed than plasma exchange. Giving intravenous immunoglobulin after plasma exchange did not confer significant extra benefit. In children, intravenous immunoglobulin probably hastens recovery compared with supportive care alone. More research is needed in mild disease and in treatment starting more than two weeks after onset of the condition. Dose-ranging studies are also needed. Guillain-Barr syndrome after H1N1 vaccination in the United States: a report using the CDC/FDA Vaccine Adverse Event Reporting System (2009). Although the Guillain-Barr syndrome (GBS) can be associated with the seasonal influenza vaccine, there is no definite evidence that GBS is associated with H1N1 influenza vaccination. The objective of this report is to study the occurrence and characteristics of GBS after H1N1 vaccine administration in the United States in 2009. Data were acquired from the Vaccine Adverse Event Reporting System and supplemented by additional information obtained from the Center for Biologics Evaluation and Research, under the Federal Freedom of Information Act. A total of 62 individuals (mean age 46.51 22.41 years), 33 of whom were men, developed GBS associated with the H1N1 influenza vaccination in 2009. Sixty GBS cases were reported within 6 weeks after vaccination, with 31 cases (50.0%) reported in the first 2 weeks. The estimated rate of occurrence of GBS was 6.2 cases per 10 million vaccinations, which is comparable to the rate of GBS in the general population.

The higher rate of GBS reports in the first 6 weeks after H1N1 vaccination suggests that some GBS cases may be triggered by H1N1 vaccination. This warrants early recognition, treatment, and active surveillance in the postvaccination setting.