Predicting toric soft lens acuity by attenuated cylinder refraction

Purpose: As variability in vision with a toric soft contact lens is related to cylinder power, providing the lowest acceptable amount of cylinder correction is sometimes a useful strategy. It would be useful clinically to have a reliable method of testing the acceptability of reduced cylinder correction prior to actually selecting and placing a trial soft toric contact lens on the eye. It would be useful to determine a patient\u27s potential acceptance of a cylinder power and axis that is adjusted to those available in the soft contact lens. Method: 18 myopic subjects (29 eyes), with astigmatism between 0.50D and 1.75D were evaluated. After determining optimal manifest refraction, the cylinder component of the refraction was adjusted to comply with those available in a single use toric soft lens such that the cylinder values and axes in the phoropter were set at -0.75 axis 180 degrees for with-the-rule eyes and -0.75 axis 90 degrees for against-the-rule eyes. Sphere power was then adjusted to best subjective acuity. High and low contrast visual acuity was determined through this attenuated refraction. Focus Dailies Toric lenses with power corresponding to the attenuated refraction were applied and allowed to settle. High and low contrast acuity were determined again, and compared with acuity obtained with the attenuated refraction. Results: Analysis showed a reasonably linear relationship between the visual acuities obtained from the adjusted refraction and the trial contact lens, with a trend to better acuity with the contact lens. Acuity with the contact lens was the same or better than the attenuated refraction for 93% of eyes. Conclusion: Practitioners performing an attenuated cylinder refraction prior to selecting a soft toric contact lens should be able to reliably predict the patient\u27s visual acuity with the contact lenses

Tetrahydropyrazolo[1,5-a]Pyrimidine-3-Carboxamide and N-Benzyl-6′,7′-Dihydrospiro[Piperidine-4,4′-Thieno[3,2-c]Pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-ca​rboxamide(THPP) and N-benzyl-6′,7′-dihydrospiro[piperidine-4,​4′-thieno[3,2-c]pyran](Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This ‘genetic phenotype’ was further confirmed by a ‘chemical phenotype’, whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice