Dupilumab-associated ocular surface disease: An interdisciplinary decision framework for prescribers in the Australian setting.

BACKGROUND/OBJECTIVES: Dupilumab-associated ocular surface disease (DAOSD) is of particular relevance in patients with atopic dermatitis (AD). Guidance on DAOSD assessment and management in the Australian setting is needed to reduce its impact and minimise disruption to treatment. METHODS: A systematic review of the literature was undertaken to identify data pertaining to the incidence, pathophysiology, risk factors and management of DAOSD. A critical review of this literature was used to inform a decision framework for dupilumab-prescribers and develop a graded severity scoring tool to guide appropriate management options. RESULTS: DAOSD typically emerges within 4 months of commencing dupilumab and the occurrence of new events diminishes over time. The reported incidence varies widely depending on the nature and source of the data: 8.6-22.1% (clinical trials programme), 0.5-70% (real-world data; differences in study size, duration of follow-up, ophthalmologist intervention, use of prophylaxis). Occurrence increases with AD severity and in patients with prior history of ocular disease; pathophysiology is still to be fully characterised. Management options have evolved over time and include lubricants/artificial tears, corticosteroids, calcineurin inhibitors, antihistamines, anti-inflammatory agents and antimicrobial agents. Current therapies aim to resolve symptoms or reduce severity to levels sufficiently tolerable to enable continuation of dupilumab therapy. CONCLUSIONS: Recommendations for DAOSD assessment and management include identification of high-risk patients, vigilance for red flags (keratoconus, herpetic and bacterial keratitis), regular assessment of symptom severity (before and during dupilumab therapy), conservative management of mild DAOSD by the prescribing physician and ophthalmologist referral for collaborative care of moderate-severe DAOSD and high-risk patients.

Immediate and short term visual recovery after SmartSurfACE photorefractive keratectomy / Recuperación visual inmediata y a corto plazo tras queratectomía fotorrefractiva SmartSurf ACE

PURPOSE: To investigate immediate and short-term visual recovery in a large cohort of 2093 myopic eyes (with or without astigmatism) treated with SmartSurfACE procedure, a combination of Transepithelial Photo Refractive Keratectomy (PRK) and Smart Pulse Technology (SPT, SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany). METHODS: In this retrospective case series, post-operative outcomes were evaluated immediately after the surgery (Day 0), at day 1 and 3 months postoperatively, after myopic SmartSurfACE treatment with mean pre-operative spherical equivalent -4.65 ± 2.53 D and range from -16.13D to- 0.13D. In all cases, pre and postoperative standard examinations were performed. The analysis evaluated preoperative Corrected and Uncorrected Distance Visual Acuity (CDVA and UDVA, respectively), and postoperative UDVA, monocularly and binocularly, immediately after the surgery, at day 1 and 3 month follow up. RESULTS: Sixty-two percent eyes achieved monocular UDVA 20/40 or better immediately after the surgery, while 82% patients achieved binocular UDVA 20/32 or better immediately after the surgery. At 3-month postoperatively, monocular UDVA 20/25 or better was achieved in 94% eyes. Treated eyes achieved immediately after the surgery or by the next day mean UDVA 20/41 ± 8. UDVA improved significantly from Day 1 to 3-months follow up (p < 0.0001 for both OS and OD) to mean UDVA 20/21 ± 5 (equal to preoperative CDVA 20/21 ± 8). CONCLUSION: Immediate and short-term visual recovery after SmartSurfACE PRK in our large cohort was rapid, providing functional binocular UDVA immediately after the surgery

OBJETIVO: Investigar la recuperación visual inmediata y a corto plazo en una amplia cohorte de 2.093 ojos miópicos (con o sin astigmatismo) tratados con el procedimiento SmartSurfACE, una combinación de Queratectomía Fotorrefractiva Transepitelial (PRK) y SPT (Smart Pulse Technology, SCHWIND eye-tech-solutions GmbH, Kleinostheim, Alemania). MÉTODOS: En esta serie de casos retrospectivos, se evaluaron los resultados post-operatorios inmediatamente tras la cirugía (Día 0), al día siguiente a la misma, y a los tres meses de la intervención, tras el tratamiento de la miopía con SmartSurfACE, con un equivalente esférico preoperatorio medio -4,65 ± 2,53D y rango desde -16,13D a -0,13D. En todos los casos se realizaron exámenes estándar preoperatorios y postoperatorios. El análisis evaluó preoperatoriamente la agudeza visual de lejos corregida y no corregida (CDVA y UDVA), y postoperatoriamente UDVA, monocular y binocular, inmediatamente tras la cirugía, al día siguiente, y a los tres meses de seguimiento. RESULTADOS: El 62% de los ojos logró UDVA monocular 20/40 o un valor mejor inmediatamente tras la cirugía, y el 82% de los pacientes logró UDVA binocular 20/32 o un mejor valor inmediatamente tras la cirugía. A los tres meses de la intervención, se logró UDVA monocular 20/25 o un valor mejor en el 94% de los ojos. Los ojos tratados lograron inmediatamente tras la cirugía o al día siguiente UDVA 20/41 ± 8. UDVA mejoró significativamente entre el día siguiente y los tres meses de seguimiento (p < 0,0001 para ambos ojos) a un valor medio de 20/21 ± 5 (igual a CDVA preoperatoria de 20/21 ± 8). CONCLUSIÓN: La recuperación visual inmediata y a corto plazo tras PRK con SmartSurfACE en nuestra amplia cohorte fue rápida, logrando una UDVA binocular funcional inmediatamente tras la cirugía

Immediate and short term visual recovery after SmartSurfACE photorefractive keratectomy.

PURPOSE: To investigate immediate and short-term visual recovery in a large cohort of 2093 myopic eyes (with or without astigmatism) treated with SmartSurfACE procedure, a combination of Transepithelial Photo Refractive Keratectomy (PRK) and Smart Pulse Technology (SPT, SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany). METHODS: In this retrospective case series, post-operative outcomes were evaluated immediately after the surgery (Day 0), at day 1 and 3 months postoperatively, after myopic SmartSurfACE treatment with mean pre-operative spherical equivalent -4.65±2.53D and range from -16.13D to -0.13D. In all cases, pre and postoperative standard examinations were performed. The analysis evaluated preoperative Corrected and Uncorrected Distance Visual Acuity (CDVA and UDVA, respectively), and postoperative UDVA, monocularly and binocularly, immediately after the surgery, at day 1 and 3 month follow up. RESULTS: Sixty-two percent eyes achieved monocular UDVA 20/40 or better immediately after the surgery, while 82% patients achieved binocular UDVA 20/32 or better immediately after the surgery. At 3-month postoperatively, monocular UDVA 20/25 or better was achieved in 94% eyes. Treated eyes achieved immediately after the surgery or by the next day mean UDVA 20/41±8. UDVA improved significantly from Day 1 to 3-months follow up (p<0.0001 for both OS and OD) to mean UDVA 20/21±5 (equal to preoperative CDVA 20/21±8). CONCLUSION: Immediate and short-term visual recovery after SmartSurfACE PRK in our large cohort was rapid, providing functional binocular UDVA immediately after the surgery.

High-Dose Steroid Treatment of Bacterial Keratitis.

PURPOSE: To describe the usage patterns of steroids in bacterial keratitis and to analyze the effect of steroids on patients' visual outcomes. METHODS: This was a single-center retrospective review of patients with culture-positive bacterial keratitis treated between 1999 and 2015 at Princess Alexandra Hospital (Brisbane, Australia). Patients with culture-positive bacterial keratitis were identified through the Queensland Pathology Database, and clinical information was gathered through a subsequent medical record review. High-dose steroid treatment was classified as 6 or more drops of a steroid a day started within 7 days of corneal scraping. The outcome of a patient's episode of keratitis was classified as good if their final visual acuity was 6/12 or better; poor if it was 6/60 or worse or required a corneal transplant, otherwise it was classified as average. Microbiological and clinical variables' association with outcomes was evaluated in univariate analyses. Variables significant at P < 0.1 were examined in a multivariate ordinal logistic regression analysis created with forward variable selection with forced inclusion of steroid treatment (high, regular, low dose, and none). RESULTS: A total of 328 patients were included from the 1002 reviewed charts. Of these patients, 164 (50.0%) were treated with steroids. Factors significantly associated with outcomes in the multivariate model were high-dose steroid treatment, visual acuity on presentation, age group, cause of keratitis, infiltrate size, and location. The odds ratio of better outcomes with high-dose steroids was 5.49 (confidence interval, 1.6-19.0, P = 0.007). CONCLUSIONS: High-dose steroid treatment is significantly associated with better visual outcomes in patients with culture-positive bacterial keratitis in this case series.

Postoperative Corneal Asphericity in Low, Moderate, and High Myopic Eyes After Transepithelial PRK Using a New Pulse Allocation.

PURPOSE: To evaluate the postoperative asphericity in low, moderate, and high myopic eyes after combined transepithelial photorefractive keratectomy and SmartSurfACE treatment (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany). METHODS: In this retrospective case series, the outcomes of myopic SmartSurfACE were evaluated at 3 months postoperatively in 106 eyes and divided into low (less than -4.125 diopters [D]), moderate (-4.125 to -6.25 D), and high (more than -6.25 D) myopia groups. In all cases, standard examinations and preoperative and postoperative corneal topography (SCHWIND Sirius) were performed. The analysis comprised evaluating the change in asphericity versus planned correction, comparing expected and achieved postoperative asphericity for all eyes, and comparison of the three groups in terms of the preoperative and postoperatively expected and achieved asphericity. RESULTS At 3 months postoperatively, the low myopia group (n = 33) improved average negative asphericity (Q = -0.04 ± 0.17 preoperative vs -0.19 ± 0.20 postoperative, P < .05). The moderate myopia group (n = 35) maintained or slightly improved average negative asphericity (Q = -0.07 ± 0.14 preoperative vs -0.05 ± 0.24 postoperative, P = .35). For the high myopia group (n = 38), the eyes became more oblate compared to the preoperative status (Q = -0.09 ± 0.15 preoperative vs 0.62 ± 0.70 postoperative, P < .05). In terms of asphericity, the difference between the three groups was not statistically significant preoperatively (P > .10), but showed significant differences postoperatively (P < .007). The cohort's average preoperative corrected distance visual acuity was 0.01 ± 0.04 logMAR (range: 0.0 to 0.18 logMAR) and uncorrected distance visual acuity was 0.03 ± 0.08 logMAR (range: -0.12 to 0.40 logMAR) 3 months postoperatively. CONCLUSIONS: SmartSurfACE maintained or slightly improved preoperative corneal asphericity for low to moderate myopic corrections (up to -6.00 D). This may provide advantages in the quality of vision and the onset of presbyopic symptoms after laser refractive surgery in myopic patients. [J Refract Surg. 2017;33(12):820-826.].

Accelerated search for materials with targeted properties by adaptive design.

Finding new materials with targeted properties has traditionally been guided by intuition, and trial and error. With increasing chemical complexity, the combinatorial possibilities are too large for an Edisonian approach to be practical. Here we show how an adaptive design strategy, tightly coupled with experiments, can accelerate the discovery process by sequentially identifying the next experiments or calculations, to effectively navigate the complex search space. Our strategy uses inference and global optimization to balance the trade-off between exploitation and exploration of the search space. We demonstrate this by finding very low thermal hysteresis (ΔT) NiTi-based shape memory alloys, with Ti50.0Ni46.7Cu0.8Fe2.3Pd0.2 possessing the smallest ΔT (1.84 K). We synthesize and characterize 36 predicted compositions (9 feedback loops) from a potential space of ∼800,000 compositions. Of these, 14 had smaller ΔT than any of the 22 in the original data set.

Adaptive Strategies for Materials Design using Uncertainties.

We compare several adaptive design strategies using a data set of 223 M2AX family of compounds for which the elastic properties [bulk (B), shear (G), and Young's (E) modulus] have been computed using density functional theory. The design strategies are decomposed into an iterative loop with two main steps: machine learning is used to train a regressor that predicts elastic properties in terms of elementary orbital radii of the individual components of the materials; and a selector uses these predictions and their uncertainties to choose the next material to investigate. The ultimate goal is to obtain a material with desired elastic properties in as few iterations as possible. We examine how the choice of data set size, regressor and selector impact the design. We find that selectors that use information about the prediction uncertainty outperform those that don't. Our work is a step in illustrating how adaptive design tools can guide the search for new materials with desired properties.