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High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment for chemosensitive relapsed classical Hodgkin lymphoma, although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR classical Hodgkin lymphoma patients treated with HDC/ASCT at our institution between 01/01/2005 and 12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring more than one salvage line, or positron emission tomography (PET)-positive disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (n=146), busulphan/melphalan (BuMel) (n=38), gemcitabine( Gem)/BuMel (n=189) and vorinostat/Gem/BuMel (n=128). The Gem/BuMel and vorinostat/Gem/BuMel cohorts had more HRR criteria and more patients with PET-positive disease at ASCT. Treatment with brentuximab vedotin (BV) or anti-PD1 prior to ASCT, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). The median follow-up is 50 months (range, 6-186). Outcomes improved over time, with 2-year progressionfree survival (PFS)/overall survival (OS) rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016- 2019) (P

Significance Alignment of the scleral lens haptic with the anterior ocular surface is of critical importance when fitting scleral lenses. The concept of leveraging big-data analysis to drive lens design is explored in this study. This retrospective study evaluated fitting outcomes of a data-driven, quadrant-specific scleral lens design and found that most patients (76%) were successfully fit with this design. Purpose The purpose of this study was to evaluate clinical outcomes with a data-driven, quadrant-specific scleral lens design compared with traditional lens designs. Methods For this multicenter retrospective observational study, A REDCap (Research Electronic Data Capture) survey was distributed to scleral lens practitioners who participated in β testing of a data-driven, quadrant-specific scleral lens design (study lens) between June 1, 2016, and January 31, 2017. Descriptive data were collected, and patient-reported outcomes, visual acuity, and lens design outcomes achieved with the study lens were described. Results Seventy-five patients (85 eyes) were fit with the study lens design between June 2016 and January 2017. Mean patient age was 47 years (range, 17 to 77 years). Forty-six were male, and 29 were female. Seventy-six eyes (89%) were fit for corneal irregularity, whereas nine eyes (11%) were fit for management of ocular surface disease. Compared with habitual correction, 22% more eyes achieved 20/20 or better, and 21% more eyes achieved 20/40 or better. There was also a 60% decrease in the need for midday removal with the study lens. An average of two lenses were manufactured per eye to complete the fitting process. Conclusions Using a data-driven, quadrant-specific scleral lens resulted in visual improvement, a reduced need for midday removal, and an average of two lenses needed to complete the fitting process. Longer-term clinical outcomes and the use of big-data analysis to inform scleral lens design should be further explored.

PURPOSE BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. METHODS We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698 ) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed. RESULTS Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement. CONCLUSION Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.

Scleral lenses were the first type of contact lens, developed in the late nineteenth century to restore vision and protect the ocular surface. With the advent of rigid corneal lenses in the middle of the twentieth century and soft lenses in the 1970's, the use of scleral lenses diminished; in recent times there has been a resurgence in their use driven by advances in manufacturing and ocular imaging technology. Scleral lenses are often the only viable form of contact lens wear across a range of clinical indications and can potentially delay the need for corneal surgery. This report provides a brief historical review of scleral lenses and a detailed account of contemporary scleral lens practice including common indications and recommended terminology. Recent research on ocular surface shape is presented, in addition to a comprehensive account of modern scleral lens fitting and on-eye evaluation. A range of optical and physiological challenges associated with scleral lenses are presented, including options for the clinical management of a range of ocular conditions. Future applications which take advantage of the stability of scleral lenses are also discussed. In summary, this report presents evidence-based recommendations to optimise patient outcomes in modern scleral lens practice.

Objectives To compare lens comfort and dry eye (DE) symptoms of DE scleral lens (SL) wearers fit with polyethylene glycol (PEG)-based surface-treated and untreated SLs. Dry eye signs, comfortable SL wearing time (WT), vision quality, and lens-related ocular surface changes were also assessed. Methods Twenty-one SL wearers with DE and SL discomfort were enrolled in a double-masked crossover study. Participants were randomized to wear their untreated or PEG (Tangible Hydra-PEG, Tangible Science; Redwood, CA) surface-treated SL of the same parameters first for 30 days. Lens comfort, DE symptoms, and ocular surface assessments were measured at baseline, after the first test period, and after the crossover. Comfortable lens WT and frequency of foggy vision were recorded. Comparisons were assessed using paired t tests or Wilcoxon signed-rank tests. Results Polyethylene glycol-treated SL wear resulted in significantly improved: lens comfort (P=0.003), DE symptoms (P=0.004), corneal sodium fluorescein staining (P=0.01), temporal conjunctival lissamine green staining (P=0.01), lid wiper epitheliopathy (P=0.002), conjunctival papillae (P=0.003), frequency of foggy vision (P=0.002), tear break-up time (TBUT) (P=0.01), and comfortable lens WT (P=0.002) compared with untreated wear. There were no significant changes between treated and untreated lens wear for TBUT over the SL (P=0.14) and nasal conjunctival lissamine green staining (P=0.06). Conclusions Polyethylene glycol surface-treated SLs provided improved comfort, reduced DE symptoms, and reduced ocular surface compromise compared with untreated SLs for participants with DE.

SIGNIFICANCE Standardized guidelines that are clinically practical are needed to assist the prescriber in minimizing the risk of conveying infection through multiuse diagnostic contact lens use and reuse.Contact lens prescribers face the specter of transferring potential pathogens from one patient to another when reusing diagnostic (trial) contact lenses on multiple patients because infectious organisms have been recovered from worn contact lenses, although there is no evidence of transmission through this mechanism. These pathogens can be introduced into the system from one patient to another, or they may be introduced by clinician lens handling, storage, or both. These pathogens can cause acute or chronic systemic or ocular infection that can lead to significant morbidity (temporary or permanent) that includes vision loss.

The use of contact lenses as ocular drug delivery systems has been considered intuitive for decades. However, at this time, there are no approved products using such systems. In this article, we review the challenges with current therapies, pharmacokinetics, and pharmacodynamics of different drug classes and the patient population. In addition, we note the relative lack of clinical studies, and list potential products in active development at this time. In particular, we address the alignment of time course of the therapeutic need, the pharmacokinetics of the molecule, and the delivery characteristics of the systems (e.g., pulsatile vs. zero-order). We also discuss the needs of various populations including the elderly (who may have motor and cognitive issues as well as presbyopia) and the young. While a contact lens delivery system may also provide refractive correction, to date, most of the studies have used noncorrective (plano) lenses. We also considered nanotechnology-based carrier systems. We generalize the development of contact lens delivery systems to all ocular delivery systems in which there are relatively few product approvals and long development times.

Purpose Diagnostic testing for dry eye disease (DED) in Sjogren's syndrome (SS) is well described. Little is published about monitoring this systemic autoimmune DED. We analyzed the SS related DED tests used in North American optometric practices and compared academic settings to private practice settings. Methods A retrospective chart review of 123 SS charts from 6 optometric practices in North America was conducted. Testing done during the first examination following a SS diagnosis was recorded on Research Electronic Data Capture (REDCap) database. The complete data file was reviewed and testing type and methodology were compared. Results Symptoms of DED (98.4% of charts),meibomian gland dysfunction (76.4% of charts), corneal staining with fluorescein (75.6% of charts) and anterior blepharitis (73.2% of charts) were the most frequently recorded variables. Clinicians used different methodologies to measure and grade these variables. Private practitioners were more likely to use symptom questionnaires and grading scales and to describe anterior blepharitis. Academic settings were more likely to record TBUT and tear meniscus height. Conclusions The monitoring of DED in SS is not uniform in optometric offices across North America. Creating accepted standards of testing will improve the ability of clinicians and researchers to communicate and understand the course of DED in SS.

Purpose We performed a needs assessment to understand how existing physician assistant (PA) program curricula and clinical training affect students' ultrasound knowledge, skills, and competence and prepare students for performing ultrasound techniques in clinical practice. Methods Students graduating from a PA program completed a 23-item questionnaire examining their ultrasound training experiences, their self-assessment of competency, and their demographics. Students also completed a 15-item ultrasound knowledge assessment. Results Thirty-eight of 39 students (97%) completed the survey. Students received little hands-on ultrasound training, with the most hands-on training being offered during emergency medicine (44.7%), obstetrics and gynecology (42.1%), and inpatient internal medicine (39.5%) rotations. This lack of preparedness was reflected in a mean score of 47.1% (±16.4%) on the ultrasound knowledge assessment. Most students (84.2%) indicated that the ultrasound instruction they received during clinical rotations was insufficient to prepare them for clinical practice, and 84.2% desired a formal ultrasound training program in the PA program curriculum. Conclusions Existing PA program curricula are insufficient for developing critical skills related to ultrasonography.

To assess the existing literature on the subject of keratoconus and personality and to propose a theory that might account for the perceived personality changes associated with this condition.A literature search was conducted in the PubMed database using the term "keratoconus" in combination with keywords such as personality, psychiatry, psychology, anxiety, depression, or psychosis. A total of 15 articles pertaining to personality and psychiatric disorders in keratoconus were retained and reviewed.Although patients with keratoconus tend to score differently on personality scales compared with normal controls, the literature fails to substantiate the existence of a unique "keratoconic personality." Instead, patients with keratoconus prove to have more dysfunctional coping mechanisms that specifically alter their interaction with health care providers and may account for the persistent clinical impression of less respectful, conforming, and cooperative patients.We hypothesize that the stage of life at which keratoconus commonly presents plays a crucial role in personality and coping mechanism development that significantly affects behavioral patterns and the relationship with caregivers.

The aim of this study was to evaluate both the indications for and results of fitting the Jupiter Scleral Lens in patients with corneal abnormalities.This was a retrospective case review of 63 patients (107 eyes) fitted with scleral lenses between October 2009 and March 2011 at the UC Davis Eye Center.Sixty-three percent of 107 eyes were in patients with keratoconus. Other conditions included high postkeratoplasty astigmatism and corneal scarring. The improvement in best-corrected visual acuity compared with previous contact lens or glasses correction was a mean gain of 3.5 Snellen lines (SD=2.6). Seventy-eight percent of patients found the scleral lenses to be comfortable or comfortable. Twenty-five eyes discontinued the wear after at least 3 months.Jupiter Scleral lenses are a good alternative for patients with corneal abnormalities and for those who failed other types of lens rehabilitation. Seventy-seven percent of eyes fit with Jupiter Scleral Lenses were still wearing after a follow-up of 3 months.

The range of contact lens modalities currently available for the successful optical correction of keratoconus is greatly expanded. We review lens types currently available for the nonsurgical management of keratoconus, including rigid gas-permeable (GP) lenses, intralimbal lenses, corneoscleral lenses, scleral lenses, hybrid lenses, and piggyback lenses. In this review, we discuss the contemporary range of available lens types and the circumstances in which they are best used.

To examine the clinical outcomes of scleral lenses for visual rehabilitation after penetrating keratoplasty (PK).A retrospective review was conducted for 34 patients (48 eyes) who had a history of prior PK and were fit with scleral lenses between October 2009 and December 2013 at the UC Davis Eye Center.The most common initial indication for PK was keratoconus in 27 eyes (56%). Thirty-three eyes (69%) had previously been fit with other types of contact lenses, with small-diameter rigid gas-permeable lenses being the most common. The improvement in best-corrected visual acuity with a scleral lens compared with prior spectacle refraction or other contact lens was a mean of two best-corrected visual acuity lines. Forty-four eyes (91.7%) achieved functional vision with best scleral lens-corrected visual acuities of 20/40 or better. Patients who continued wearing scleral lenses were significantly more likely to report "good" subjective vision compared with patients who abandoned scleral lens wear (P=0.009), although change in objective best-corrected visual acuity did not differ significantly. There were no cases of infectious keratitis. Six eyes (12.5%) developed graft rejection; 3 were able to resume scleral lens wear. Nineteen eyes (39.5%) discontinued scleral lens wear for various reasons, the most common reason for discontinuation of lens wear was difficulty with scleral lens insertion or removal (8 eyes, 42.1%).Scleral lenses are effective and safe in patients who have had PK. There was a mean gain in visual acuity, with the majority of patients achieving 20/40 vision or better. The patient's subjective perception of vision was a significant factor in determining whether scleral lens wear was continued or abandoned.