Long-term efficacy of botulinum toxin A for treatment of blepharospasm,hemifacial spasm, and spastic entropion: a multicentre study using two drug-dose escalation indexes

PURPOSE: To investigate the long-term effectiveness and safety of botulinum neurotoxin A (BoNT-A) treatment in patients with blepharospasm (BEB), hemifacial spasm (HFS), and entropion (EN) and to use for the first time two modified indexes, 'botulin toxin escalation index-U' (BEI-U) and 'botulin toxin escalation index percentage' (BEI-%), in the dose-escalation evaluation. METHODS: All patients in this multicentre study were followed for at least 10 years and main outcomes were clinical efficacy, duration of relief, BEI-U and BEI-%, and frequency of adverse events. RESULTS: BEB, HFS, and EN patients received a mean BoNT-A dose with a significant inter-group difference (P<0.0005, respectively). The mean (+/-SD) effect duration was statistically different (P=0.009) among three patient groups. Regarding the BoNT-A escalation indexes, the mean (+/-SD) values of BEI-U and BEI-% were statistically different (P=0.035 and 0.047, respectively) among the three groups. In BEB patients, the BEI-% was significantly increased in younger compared with older patients (P=0.008). The most frequent adverse events were upper lid ptosis, diplopia, ecchymosis, and localized bruising. CONCLUSIONS: This long-term multicentre study supports a high efficacy and good safety profile of BoNT-A for treatment of BEB, HFS, and EN. The BEI indexes indicate a significantly greater BoNT-A-dose escalation for BEB patients compared with HFS or EN patients and a significantly greater BEI-% in younger vsolder BEB patients. These results confirm a greater efficacy in the elderly and provide a framework for long-term studies with a more flexible and reliable evaluation of drug-dose escalation

Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)

The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death

Conjunctival Reconstruction with Progenitor Cell-Derived Autologous Epidermal Sheets in Rhesus Monkey

Severe ocular surface diseases are some of the most challenging problems that the clinician faces today. Conventional management is generally unsatisfactory, and the long-term ocular consequences of these conditions are devastating. It is significantly important to find a substitute for conjunctival epithelial cells. This study was to explore the possibility of progenitor cell-derived epidermal sheets on denuded amniotic membrane to reconstruct ocular surface of conjunctiva damaged monkeys. We isolated epidermal progenitor cells of rhesus monkeys by type IV collagen adhesion, and then expanded progenitor cell-derived epidermal sheets on denuded amniotic membrane ex vivo. At 3 weeks after the conjunctiva injury, the damaged ocular surface of four monkeys was surgically reconstructed by transplanting the autologous cultivated epidermal progenitor cells. At 2 weeks after surgery, transplants were removed and examined with Hematoxylin-eosin staining, Periodic acid Schiff staining, immunofluorescent staining, scanning and transmission electron microscopy. Histological examination of transplanted sheets revealed that the cell sheets were healthy alive, adhered well to the denuded amniotic membrane, and had several layers of epithelial cells. Electron microscopy showed that the epithelial cells were very similar in appearance to those of normal conjunctival epithelium, even without goblet cell detected. Epithelial cells of transplants had numerous desmosomal junctions and were attached to the amniotic membrane with hemidesmosomes. Immunohistochemistry confirmed the presence of the conjunctival specific markers, mucin 4 and keratin 4, in the transplanted epidermal progenitor cells. In conclusion, our present study successfully reconstructed conjunctiva with autologous transplantation of progenitor cell-derived epidermal sheets on denuded AM in conjunctival damaged monkeys, which is the first step toward assessing the use of autologous transplantation of progenitor cells of nonocular surface origin. Epidermal progenitor cells could be provided as a new substitute for conjunctival epithelial cells to overcome the problems of autologous conjunctiva shortage

Improving Results in Endoscopic DCR

The aim of presenting this article is to highlight the factors causing failure in endoscopic dacryocystorhinostomy (DCR). Understanding these factors will lead to an enhancement in the success rate of endoscopic DCR. Out of 600 cases done in a period of 10 years (from 1998 to 2008), 60 were revision cases. 60 patients referred over a period of 10 years, were selected. The aim was to study the factors causing failure in each case. The cases included were revised in a period of 10 years from 1998 to 2008. These were the cases that were unsuccessful for one or the other reason. The author presents a series of failed DCR cases referred over a period of 10 years. Patients had undergone primary surgery elsewhere and were referred due to the persistence of symptoms. Assessment of all the cases was done with the examination of Eyes and lids for any obvious deformity, watering or purulent discharge in the medial canthal area. ROPLAS test was done as a spot diagnosis for NLD block. This was followed by probing and syringing in the outdoor. All the cases were revised and the likely causes leading to failure of the first surgery were analyzed. It was found that the improper selection of cases accounted for 3.3% of total failed cases; Low rhinostomy accounted for 28.3% cases, inadequate sac opening for 38.3% cases, Pre existing canaliculitis for 1.6% of cases, contracture at the rhinostomy site in 10% cases. Laser burn canalicular scarring for 3.3% of total cases and laxity of the lids and atonic sac was responsible for failure in 3.3% cases. Most of the above factors are secondary to the false localization of the sac, inadequate removal of the sac wall, too much of mucosal removal leading to synaechia formation at the surgical site and inability to detect any additional block with NLD (Nasolacrimal duct) block

External dacryocystorhinostomy: do we really need to repair the posterior flap?

Purpose: This study aims to compare a simplified technique of external dacryocystorhinostomy (DCR), where the posterior flap is excised, with the more traditional approach of double flap repair. Methods: A prospective, comparative, single surgeon, single centre clinical trial was conducted of eighty-three patients who received external DCR, with either anterior and posterior flap anastomosis (Group A), or anterior flap anastomosis and excision of the posterior flap (Group B), in a tertiary referral hospital in Nepal. Patients with nasolacrimal duct obstruction and epiphora were assigned to one of two groups. Follow up was a minimum of 6 months for inclusion in the study. Success was defined objectively by irrigation of the puncta without regurgitation and subjectively by the absence of epiphora or discharge. Results: The overall success rate of external DCR was 89.2%, after a mean follow up of 13.5 ± 2.2 months. There was no difference in success between the two groups (p-value = 0.73), with 90.7% success in Group A and 87.5% in Group B. The frequency of complications was not statistically different between Groups A and B (p-value = 0.79). Conclusions: Excision of the posterior flap and anastomosis of only the anterior flap is not disadvantageous to the outcomes of external DCR surgery when compared with the more traditional approach of anastomosis of both flaps. We believe this simplified procedure can be implemented as the standard technique for external DCR, particularly in developing nations such as Nepal