Pre-extensively Drug-Resistant Congenital Tuberculosis in an Extremely Premature Baby.

We describe a case of congenital tuberculosis in an extremely premature baby, with rapid molecular detection of a pre-extensively drug-resistant (XDR) pattern of drug resistance. The baby was treated successfully with a regimen including bedaquline and delamanid, drugs not previously described in the treatment of congenital tuberculosis (TB).

Dry eye disease in the young: A narrative review.

Dry eye disease (DED), a multifactorial ocular disease that significantly impacts quality of life, is most commonly reported in adults. This review describes the prevalence, risk factors, diagnosis and management of DED in children. A literature search, conducted from January 2000-December 2022, identified 54 relevant publications. Using similar diagnostic criteria to those reported in adults, namely standardized questionnaires and evaluation of tear film homeostatic signs, the prevalence of DED in children ranged from 5.5% to 23.1 %. There was limited evidence for the influence of ethnicity in children, however some studies reported an effect of sex in older children. Factors independently associated with DED included digital device use, duration of digital device use, outdoor time and urban living, Rates of DED were higher in children with ocular allergy and underlying systemic diseases. Compared with similar studies in adults, the prevalence of a prior DED diagnosis or a diagnosis based on signs and symptoms was lower in children, but symptoms were commonly reported. Treatment options were similar to those in adults, including lifestyle modifications, blinking, management of lid disease and unpreserved lubricants in mild disease with escalating treatment with severity. Management requires careful exploration of symptoms, medical history and the diagnosis and management of ocular comorbidities such as allergy and anterior blepharitis. Appropriately powered population-based studies are required to understand the prevalence of and risk factors for DED in children. Development of age-appropriate thresholds for signs and symptoms of DED would support better diagnosis of disease and understanding of natural history.

Possible Strategies to Mitigate Placebo or Vehicle Response in Dry Eye Disease Trials: A Narrative Review.

Many candidate drugs for dry eye disease (DED) have been assessed over the years in pursuit of demonstrating efficacy in both signs and symptoms. However, patients with DED have very limited treatment options for management of both signs and symptoms of DED. There are several potential reasons behind this including the placebo or vehicle response, which is a frequent issue observed in DED trials. A high magnitude of vehicle response interferes with the estimation of a drug's treatment effect and may lead to failure of a clinical trial. To address these concerns, Tear Film and Ocular Surface Society International Dry Eye Workshop II taskforce has recommended a few study design strategies to minimize vehicle response observed in DED trials. This review briefly describes the factors that lead to placebo/vehicle response in DED trials and focuses on the aspects of clinical trial design that can be improved to mitigate vehicle response. In addition, it presents the observations from a recent ECF843 phase 2b study, wherein the study design approach consisted of a vehicle run-in phase, withdrawal phase, and masked treatment transition, and led to consistent data for DED signs and symptoms and reduced vehicle response post randomization.

Reduction of Artificial Tears and Use of Adjunctive Dry Eye Therapies After Lifitegrast Treatment: Evidence from Clinical and Real-World Studies.

Purpose: To assess the frequency of patients reducing the use of artificial tears (ATs) among patients with dry eye disease (DED) following lifitegrast treatment. Patients and Methods: Two independent analyses were performed using the data from the 1-year, randomized, multicenter, Phase 3 SONATA trial and a noninterventional, real-world evidence (RWE) study conducted in patients with DED who were treated with lifitegrast in the United States and Canada. In SONATA, patients who had used ATs in the lifitegrast and placebo groups were included. The RWE study reviewed patients' electronic medical records, prescribing patterns, and practices of physicians throughout the survey. These data were then used to compare the proportion of patients using ATs in the 6-month pre-index period versus the 12-month post-index period. Results: Of 293 patients (lifitegrast, n=195; placebo, n=98) from SONATA, 107 (lifitegrast, n=64; placebo, n=43) used ATs during the on-therapy period while 186 (lifitegrast, n=131; placebo, n=55) did not. Of those not using ATs, the proportion of patients in the lifitegrast group at any time was higher (~67% [n=131]) versus placebo (~56% [n=55]); this was the case at all study time-points (Days 90, 180, 270, and 360). The RWE study included 600 patient charts (US, n=550; Canada, n=50); 75.5% (n=453) reported AT use. There was ~40% decrease in the proportion of patients using ATs as adjunct DED therapy to lifitegrast in the post-index period (n=273) versus those in the pre-index period (n=453). Conclusion: The findings show that the reliance on AT use can be gradually reduced with lifitegrast treatment, eventually leading to a reduction in disease burden.

Thirty years of 'quiet eye' with etafilcon A contact lenses.

Frequent replacement contact lenses made from the etafilcon A hydrogel lens material were introduced onto the market over 30 years ago, and etafilcon A remains the most widely used hydrogel lens material today. Although the prescribing of silicone hydrogel lenses is increasing, millions of lens wearers globally have been wearing hydrogel lenses for many years and exhibit a physiologically-stable 'quiet eye', with a low profile of adverse events. Hydrogel lenses are demonstrated to maintain a low inflammatory response and infection risk profile during daily wear, which in the case of etafilcon A, may be related to its low modulus, and the naturally-protective, anti-microbial, non-denatured lysozyme absorbed into the lens from the tear fluid. Although improved corneal physiology from decreased hypoxia with silicone hydrogel lenses is well accepted, equivalent levels of corneal oxygenation are maintained during daily wear of low to medium powered hydrogel lenses, which do not impede the daily corneal de-swelling process, and do not induce clinically significant changes in ocular health. Therefore, hydrogel lenses remain an important alternative for daily wear in modern contact lens practice.

Analysis of polyvinyl alcohol release from commercially available daily disposable contact lenses using an in vitro eye model.

The purpose of this work was to determine the release of polyvinyl alcohol (PVA) from etafilcon A, omafilcon A, and nelfilcon A daily disposable hydrogel contact lenses using a novel in vitro model. PVA is an ocular lubricant that can be found in multiple formulations of artificial tears. Nelfilcon A innately contains PVA, so only the release of PVA from this lens was evaluated. Etafilcon A and omafilcon A lenses were incubated in a PBS solution containing PVA. The release of PVA was evaluated using a novel in vitro blink platform with Milli-Q water and PBS under various blink conditions and flow rates. Nelfilcon A lenses significantly released more PVA than other lenses at 0.5 and 1.5 h in both PBS and Milli-Q water (p < 0.001). For nelfilcon A, there was no statistical significance between the release profiles of PVA between the blink and no-blink conditions, or for the various flow rates (p > 0.05). All tested groups and lenses showed a burst release within the first 4.5 h and rapidly plateaued thereafter. The current study demonstrates that releasable PVA (whether through uptake or through being inherently available from the material) is loosely bound on hydrogel lenses, and the majority is released within 4.5 h. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1662-1668, 2019.

Determination of the release of PEG and HPMC from nelfilcon A daily disposable contact lenses using a novel in vitro eye model.

The traditional method to measure release of components from CLs is a vial containing a static volume of PBS (phosphate buffered saline). However, this model does not simulate physiologically relevant tear volume and natural tear flow, air exposure, and mechanical rubbing. These factors can significantly impact release kinetics. We have developed an in vitro eye model (OcuFlow) that simulates these parameters. The aim of the study was to measure the release of PEG (polyethylene glycol), and HPMC (hydroxypropyl methylcellulose) from a daily disposable hydrogel contact lens material (nelfilcon A; Dailies AquaComfort PLUS; DACP;) over 24 hrs using the OcuFlow platform. The elution of PEG and HPMC from DACP lenses was analyzed using LCMS (liquid chromatography mass spectrometry). The release of all wetting agents from the lenses followed a burst release pattern, which occurred within the first 1.5 hrs (P < 0.05). The release of PEG was greater than that of HPMC (P < 0.05). The amount of PEG and HPMC released at any given time was less than 1% of the amount in the blister pack solution. Our results suggest that HPMC and PEG are rapidly released from the CL.

Comparison of the Lubricity and Surface Roughness of 5 Cosmetic Contact Lenses.

OBJECTIVES: Cosmetic contact lenses are increasingly popular because of their eye enhancing cosmetic benefits. The pigment particles used in these lenses can impact lens surface characteristics. This article examines the surface characteristics and the differences between the clear and the pigmented regions among five limbal ring design lenses. METHODS: Scanning electron microscopy was used to determine the location and depth of the pigment particles from the lens surface. The coefficient of friction (CoF) was determined with a Basalt-MUST microtribometer at clear and pigmented regions on either the front or the back surface. Atomic force microscopy was used to determine the surface roughness of each lens in root-mean-square (RMS) units at clear and pigmented regions. A linear mixed model for repeated measures was used for the analysis of the CoF and RMS roughness to compare all lenses. RESULTS: Four lens types had pigments exposed on the surface and one lens type had pigment fully enclosed. The CoF difference between clear and pigmented regions were similar and not statistically significant (P=0.0124) for the lens type with pigments enclosed, whereas the CoF difference for the other four lens types showed statistically significant difference (P<0.0001). CONCLUSIONS: Of the lenses tested here, cosmetic contact lenses with pigments enclosed in the lens matrix provided a more consistent surface between clear and pigmented regions compared with lenses that had exposed pigments.

Demonstrating correction of low levels of astigmatism with realistic scenes.

PURPOSE AND METHOD: Modern standard visual acuity tests are primarily designed as diagnostic tools for use during subjective refraction and normally bear little relation to real-world situations. We have developed a methodology to create realistic rendered scenes that demonstrate potential vision improvement in a relevant and engaging way. Low-cylindrical refractive error can be made more noticeable by optimizing the contrast and spatial frequencies, and by testing four different visual perception skills: motion tracking, pattern recognition, visual clutter differentiation and contrast sensitivity. Using a 1.00DC lens during iteration, we created a range of still and video scenes before optimizing to a selection 3-D rendered street scenes. These were assessed on everyday relevance, emotional and visual engagement and sensitivity to refractive correction for low-cylinder astigmats (0.75-1.00DC, n=74) wearing best spherical equivalent correction and then with astigmatism corrected. RESULTS AND CONCLUSIONS: The most promising visual elements involved or combined optimized textures, distracting patterns behind text, faces at a distance, and oblique text. 91.9% of subjects (95% CI: 83.2, 97.0) reported an overall visual improvement when viewing the images with astigmatic correction, and 96% found the images helpful to determine which type of contact lens to use. Our method, which combines visual science with design thinking, takes a new approach to creating vision tests. The resultant test scenes can be used to improve patient interaction and help low cylinder astigmats see relevant, every-day benefits in correcting low levels (0.75 & 1.00DC) of astigmatism.