Solution-related in Vitro Dewetting Behavior of Various Daily Disposable Contact Lenses.

SIGNIFICANCE: The dewetting process of contact lenses (CLs) is a result of material and solution properties as well as environmental factors. This article describes an investigational approach to observe and describe dewetting characteristics of different CL material and solution combinations. PURPOSE: This study aimed to determine the in vitro dewetting characteristics of various daily disposable CLs that were assessed using a noninvasive keratograph dewetting procedure (noninvasive keratograph dry-up time). In vitro dewetting data of the same CL materials soaked in saline solution and artificial tear solution (ATS) were measured to determine additional dewetting characteristics. METHODS: Noninvasive keratograph dry-up time was measured for six different soft CL materials and three different test conditions, in their specific blister solution, after exposure to saline and an ATS. Twenty CLs of each solution/material combination were assessed after an 8-hour soaking, during a 180-second dewetting observation, and the results were expressed by area under the curve values. RESULTS: Fastest dewetting occurred for all materials when measured out of saline, indicated by the highest averaged area under the curve value of 9243.3 ± 38.3 over all lens materials. Slower dewetting was detected for all materials when measured out of their specific blister solution (7755.9 ± 37.1) and out of ATS (7988.8 ± 40.0). Intragroup results were statistically significantly different for all solutions showing the smallest differences within the ATS group ( P < .001, Kruskal-Wallis test). CONCLUSIONS: A pure saline thin film is not an ideal representation of a complex tear film layer of a healthy human because it lacks any evaporative protection by a lipid layer. The use of an ATS, which more likely mimics the natural tear film, allowed in this experimental in vitro project to decrease the gap to the in vivo field. In vitro dewetting information in connection with the blister solution allows only a theoretical conclusion about the initial lens wear after lens insertion.

Morphological characteristics of Meibomian Glands and their Influence on Dry Eye disease in contact lens wearers.

PURPOSE: Meibomian glands (MG) are now easily imaged via clinical meibography machines. The purpose of this work was to explore the utility of the known MG morphology metrics for predicting dry eye disease (DED) in contact lens (CL) wearers. METHODS: Successful and previous CL wearers were recruited. DED was diagnosed if the participant's worst eye had a reduced tear meniscus height (TMH) of <0.2 mm or non-invasive tear break-up time (NITBUT) of <10 s and a Standardized Patient Evaluation of Eye Dryness (SPEED) score >5.0. Meibography was performed and images were subjectively graded by two examiners for the following MG characteristics: distorted, tortuous, hooked, abnormal gap, overlapping, fluffy areas, tadpoling, thinned, thickened, ghost, no extension to lid margin, shortened and dropout (atrophy). DED diagnostic ability of each metric was determined with receiver operating characteristic (ROC) analysis. RESULTS: A total of 112 participants were recruited, with 18.8% having DED and 60.7% being female. The only MG morphology metrics that were marginally predictive of DED were thickened upper eyelid MGs (p = 0.046), thickened mean upper plus lower eyelid MGs (p = 0.007), and atrophy of upper eyelid MGs (p = 0.043); however, none of these metrics reached a meaningful area under the curve in ROC analysis (all <0.70). CONCLUSION: While abnormal MG morphology is likely suggestive of DED in CL wearers, none of the MG morphology metrics evaluated alone in this study had clinically meaningful predictive value for detecting DED in this group of current and previous CL wearers.

Hyperspectral imaging for perioperative monitoring of microcirculatory tissue oxygenation and tissue water content in pancreatic surgery - an observational clinical pilot study.

BACKGROUND: Hyperspectral imaging (HSI) could provide extended haemodynamic monitoring of perioperative tissue oxygenation and tissue water content to visualize effects of haemodynamic therapy and surgical trauma. The objective of this study was to assess the capacity of HSI to monitor skin microcirculation and possible relations to perioperative organ dysfunction in patients undergoing pancreatic surgery. METHODS: The hyperspectral imaging TIVITA® Tissue System was used to evaluate superficial tissue oxygenation (StO2), deeper layer tissue oxygenation (near-infrared perfusion index (NPI)), haemoglobin distribution (tissue haemoglobin index (THI)) and tissue water content (tissue water index (TWI)) in 25 patients undergoing pancreatic surgery. HSI parameters were measured before induction of anaesthesia (t1), after induction of anaesthesia (t2), postoperatively before anaesthesia emergence (t3), 6 h after emergence of anaesthesia (t4) and three times daily (08:00, 14:00, 20:00 ± 1 h) at the palm and the fingertips until the second postoperative day (t5-t10). Primary outcome was the correlation of HSI with perioperative organ dysfunction assessed with the perioperative change of SOFA score. RESULTS: Two hundred and fifty HSI measurements were performed in 25 patients. Anaesthetic induction led to a significant increase of tissue oxygenation parameters StO2 and NPI (t1-t2). StO2 and NPI decreased significantly from t2 until the end of surgery (t3). THI of the palm showed a strong correlation with haemoglobin levels preoperatively (t2: r = 0.83, p < 0.001) and 6 h postoperatively (t4: r = 0.71, p = 0.001) but not before anaesthesia emergence (t3: r = 0.35, p = 0.10). TWI of the palm and the fingertip rose significantly between pre- and postoperative measurements (t2-t3). Higher blood loss, syndecan level and duration of surgery were associated with a higher increase of TWI. The perioperative change of HSI parameters (∆t1-t3) did not correlate with the perioperative change of the SOFA score. CONCLUSION: This is the first study using HSI skin measurements to visualize tissue oxygenation and tissue water content in patients undergoing pancreatic surgery. HSI was able to measure short-term changes of tissue oxygenation during anaesthetic induction and pre- to postoperatively. TWI indicated a perioperative increase of tissue water content. Perioperative use of HSI could be a useful extension of haemodynamic monitoring to assess the microcirculatory response during haemodynamic therapy and major surgery. TRIAL REGISTRATION: German Clinical Trial Register, DRKS00017313 on 5 June 2019.

Ultraviolet and Visible Transmittance of Soft Contact Lenses with and without Ultraviolet Blockers.

SIGNIFICANCE: Ultraviolet (UV) and visible light transmittance of soft contact lenses (SCLs) was measured. A significant difference in UV transmittance has been found between SCLs with a positive and negative back vertex power (BVP). It can be shown that thicker SCLs absorb more UV radiation. PURPOSE: This study aimed to determine UV and visible light transmittance of different SCLs with and without UV protection filters. METHODS: Twenty-one lens brands were investigated in the BVP range of -12.00 to +6.00 D. Three SCLs were measured per BVP 25 times. Three hundred thirty-nine SCLs with UV filter (stenfilcon A, somofilcon A, narafilcon A, senofilcon A, senofilcon C, etafilcon A, nesofilcon A) and 489 SCLs without UV filter (delefilcon A, lotrafilcon A, lotrafilcon B, comfilcon A, balafilcon A, samfilcon A, asmofilcon A, nelfilcon A, omafilcon A, hilafilcon B, ocufilcon D, hioxifilcon A, omafilcon B) have been examined. The measurement setup was created according to ISO 18369-3. RESULTS: All UV-absorbing labeled test SCLs meet UV protection class 2. senofilcon A, senofilcon C, and narafilcon A meet the higher UV protection class 1 level. A statistically significant difference in UV transmittance (280 to 380 nm) has been found between SCLs with a positive BVP (+1.00 to +6.00 D) and SCLs with a negative BVP (-1.00 to -12.00 D), both without (P = .04) and with UV filters (P = .02). CONCLUSIONS: With the ISO-conforming, diopter-independent measurement setup, the UV-absorbing test contact lenses that meet the current international standards, regardless of their BVP, were identified. Lenses with increased center thickness absorb more UV radiation. Further studies may use a modified measurement setup with a larger aperture than 10 mm. It would also be worthwhile to examine the UV absorption of the contact lens over the complete corneal area and limbal area because UV radiation may damage inner ocular tissues like the crystalline lens as well as limbal stem cells.

In-House Preparation and Quality Control of Ac-225 Prostate-Specific Membrane Antigen-617 for the Targeted Alpha Therapy of Castration-Resistant Prostate Carcinoma.

PURPOSE: Ac-225 labeled with prostate-specific membrane antigen (PSMA-617), a transmembrane glycoprotein which is highly expressed in prostate carcinoma cells, is presently being considered a promising agent of targeted alpha therapy for the treatment of patients suffering from metastatic castration-resistant prostate cancer. In the present study, we report an optimized protocol for the preparation of therapeutic dose of Ac-225 PSMA-617 with high yield and radiochemical purity (RCP). METHODS: Ac-225 PSMA-617 was prepared by adding the peptidic precursor-PSMA-617 (molar ratios, Ac-225: PSMA-617 = 30:1) in 1 ml ascorbate buffer to Ac-225 and heating the reaction mixture at 90°C for 25 min to obtain the radiopeptide with high RCP and yield. The radiolabeled peptide was administered in patients who met the eligibility criteria and posttherapy assessment was done. RESULTS: Ten batches of Ac-225 PSMA-617 were prepared following this protocol. The radiopeptide was obtained with an adequate yield of 85%-87% and RCP of 97%-99%. CONCLUSION: The current protocol allows single-step, successful, routine inhouse radiolabeling of Ac-225 with PSMA-617 with high yield and RCP.

Objective Analysis of Pre-Lens Tear Film Stability of Daily Disposable Contact Lenses Using Ring Mire Projection.

PURPOSE: The primary objective of this study was to evaluate the in vivo pre-lens non-invasive drying-up time of two types of daily disposable contact lenses (DDCLs) after 12 hours of wear. METHODS: This prospective, randomized, single-center, cross-over pilot study evaluated 31 subjects aged 18-44 years with normal eyes and good tear film stability who were adapted current soft contact lens wearers. Subjects wore nelfilcon A and stenfilcon A DDCLs for 12 hours each on two different days. Non-invasive video keratography drying-up time (NIK-DUT) videos of each eye were recorded 12 hours after lens insertion for about 25 seconds, with a 5-minute tear film recovery time allowed between video recordings of the right and left eyes to avoid bias. Post-blink time required to reach 15% distortion of the projected rings and the speed of break-up at 15 seconds post-blink were measured at each time point and on-eye wettability was determined by ring mire projection under white light illumination. RESULTS: Mean time to reach 15% ring distortion was similar for nelfilcon A (19.25±3.20 sec) and stenfilcon A (20.24±3.02 sec) DDCLs but varied highly among subjects. The mean speed of break-up at 15 sec post-blink was 0.3±0.38% distortion/sec (95% confidence interval [CI] 0.138-0.365% distortion/sec) for nelfilcon A and 0.2±0.23% distortion/sec (95% CI 0.048-0.279% distortion/sec) for stenfilcon A DDCLs. CONCLUSION: Multifunctional topography allowed the objective evaluation of in vivo pre-lens tear film stability using ring mire projection. This dynamic method was simple, fast and non-invasive, enabling measurements of NIK-DUT and evaluating wettability over a large area, greater than the optical zone of the contact lens surface, for the entire inter-blink interval.

Bedside hyperspectral imaging for the evaluation of microcirculatory alterations in perioperative intensive care medicine: a study protocol for an observational clinical pilot study (HySpI-ICU).

INTRODUCTION: Normalisation of macrocirculatory parameters during resuscitation therapy does not guarantee the restoration of microcirculatory perfusion in critical illness due to haemodynamic incoherence. Persistent microcirculatory abnormalities are associated with severity of organ dysfunction and mandate the development of bedside microcirculatory monitoring. A novel hyperspectral imaging (HSI) system can visualise changes in skin perfusion, oxygenation and water content at the bedside. We aim to evaluate the effectiveness of HSI for bedside monitoring of skin microcirculation and the association of HSI parameters with organ dysfunction in patients with sepsis and major abdominal surgery. METHODS AND ANALYSIS: Three independent groups will be assessed and separately analysed within a clinical prospective observational study: (1) 25 patients with sepsis or septic shock (according to sepsis-3 criteria), (2) 25 patients undergoing pancreatic surgery and (3) 25 healthy controls. Patients with sepsis and patients undergoing pancreatic surgery will receive standard therapy according to local protocols derived from international guidelines. In addition, cardiac output of perioperative patients and patients with sepsis will be measured. Healthy controls undergo one standardised evaluation. The TIVITA Tissue System is a novel HSI system that uses the visible and near-infrared spectral light region to determine tissue microcirculatory parameters. HSI analysis (hand/knee) will be done in parallel to haemodynamic monitoring within defined intervals during a 72-hour observation period. HSI data will be correlated with the Sequential Organ Failure Assessment score, global haemodynamics, inflammation and glycocalyx markers, surgical complications and 30-day outcome. ETHICS AND DISSEMINATION: The protocol has been approved by the local ethics committee of the University of Heidelberg (S-148/2019). Study results will be submitted to peer-reviewed journals and medical conferences. TRIAL REGISTRATION NUMBER: DRKS00017313; Pre-results.

Lipid Analysis on Block Copolymer-containing Packaging Solution and Lens Care Regimens: A Randomized Clinical Trial.

SIGNIFICANCE: Lotrafilcon B lenses packaged in and cared for with block copolymer-containing (polyoxyethylene-polyoxybutylene; EOBO) lens care solutions resulted in lower cholesterol extraction than each of the habitual silicone hydrogel lens/multipurpose solution (MPS) regimens tested. PURPOSE: This study aimed to compare the extracted cholesterol of lotrafilcon B lenses packaged in and cared for with EOBO-containing lens care solutions with the extracted cholesterol of habitual silicone hydrogel lenses cared for with MPS not containing EOBO. METHODS: In this prospective, randomized, observer-masked parallel study, habitual wearers of senofilcon C, senofilcon A, comfilcon A, and samfilcon A contact lenses using a non-EOBO MPS were randomized 1:1 to lotrafilcon B lenses packaged in and cared for with EOBO-containing solutions or to their habitual lenses and MPS. Subjects randomized to lotrafilcon B were further randomized to one of two EOBO-containing lens care solutions, OPTI-FREE PUREMOIST or CLEAR CARE PLUS with HydraGlyde (Alcon Laboratories, Inc., Fort Worth, TX). A subset of right eye lenses was collected after wear, and total cholesterol was extracted and measured using a fluorometric enzymatic assay. RESULTS: Of 143 lenses analyzed, 95 were from subjects randomized to their habitual lenses/MPS and 48 to lotrafilcon B + EOBO lenses plus CLEAR CARE PLUS with HydraGlyde or OPTI-FREE PUREMOIST. The mean amounts of cholesterol extracted from lotrafilcon B + EOBO lenses cared for with CLEAR CARE PLUS with HydraGlyde (0.28 ± 0.18 µg/lens) and OPTI-FREE PUREMOIST (0.28 ± 0.48 µg/lens) were significantly lower than those extracted from senofilcon C (4.18 ± 3.25 µg/lens), senofilcon A (2.19 ± 2.69 µg/lens), comfilcon A (2.17 ± 1.47 µg/lens), and samfilcon A (2.07 ± 1.48 µg/lens) lenses used with MPS (P < .0001 each). CONCLUSIONS: Cholesterol sorption was significantly lower in wearers of lotrafilcon B lenses cared for with polyoxyethylene-polyoxybutylene-containing lens care solutions than in users of habitual silicone hydrogel lenses cared for with non-polyoxyethylene-polyoxybutylene MPS.

Subjective Comparison of Pre-Lens Tear Film Stability of Daily Disposable Contact Lenses Using Ring Mire Projection.

PURPOSE: To subjectively evaluate the in vivo tear film stability of three daily disposable contact lenses (DDCLs) using placido ring reflection at lens wear times of 5 mins and 8 and 12 hrs. PATIENTS AND METHODS: This prospective, randomized, observer-masked, 3-way crossover study evaluated 28 subjects with good tear film stability. In vivo tear film stability was assessed for three DDCLs (nelfilcon A, etafilcon A, omafilcon A) on three different days over 12 hrs of lens wear. Time to first distortion by non-invasive keratography drying-up time (NIK-DUTf) was assessed by reviewing the captured videos. Lens wettability was also graded subjectively by three investigators using a scale from 0 (no visible distortions) to 3 (distortions in more than one-third of the ring reflection zone). Medians were analyzed statistically. RESULTS: Mean NIKDUTf at 8 hrs was longer for nelfilcon A and shorter for etafilcon A and omafilcon A, but the differences were not significant. NIK-DUTf did not differ significantly among nelfilcon A, etafilcon A and omafilcon A DDCLs at all visits (p=0.36). Subjective wettability grades after 5 mins, 8 hrs, and 12 hrs differed significantly for etafilcon A (P <0.01) and omafilcon A (p < 0.01), but not for nelfilcon A (p = 0.05), DDCLs. CONCLUSION: Grading was sufficiently sensitive to differentiate the wettability performances of the three lens materials. Nelfilcon A maintained wettability over the wearing period, whereas etafilcon A material showed faster dewetting at 8 and 12 hrs than at 5 mins after lens insertion.

Introducing a novel in vivo method to access visual performance during dewetting process of contact lens surface.

PURPOSE: To introduce a novel in vivo method (Visual Acuity Dry Up; VADU) for testing the visual performance during the dewetting of the pre-lens tear film on a contact lens (CL). METHODS: Thirty-nine subjects were fitted with daily disposable CL (Nelfilcon A). Visual performance and dewetting characteristics of the pre-lens tear film were simultaneously assessed using a modified multifunctional topographer (Keratograph 5 M, OCULUS Optikgeräte GmbH, Wetzlar, GERMANY) and the Non-Invasive Keratograph Dry-Up Time (NIKDUT) method. Measures were taken after five minutes and eight hours of CL wear and included the Visual Acuity Dry-Up Time (VADUT; time between last blink and visual breakdown) and the Visual Acuity Dry-Up Area (VADUA; dewetted CL area at visual breakdown) at one (VA+0.1logMAR), two (VA+0.2logMAR) and three (VA+0.3logMAR) log units below maximal visual acuity (VA). RESULTS: Participants lost one, two or three log units of VA after 13.1 ± 17.4 s, 20.83 ± 21.81, 34.67 ± 29.11 (VADUT), corresponding to a dewetted CL area of 4.82 ± 6.64 mm², 9.5 ± 8.26 and 13.0 ± 8.68 (VADUA), respectively. Differences in VADUT und VADUA for all visual requirements were significant (all p < 0.05). VADUT and VADUA did not vary with CL wear duration (all p > 0.05). A median VA loss of one log unit occurred five seconds after the first dewetting. CONCLUSIONS: The novel VADU method can be used to analyze the role of the tear film stability on the visual performance during CL wear. Hereby, visual loss is quantified based on the threshold definition of the psychometric function.

Radiation Exposure to the Nuclear Medicine Personnel During Preparation and Handling of 213Bi-Radiopharmaceuticals.

Because of the excellent ability of α-particles to transfer a high amount of energy over a short tissue range, targeted α-therapy has been attracting rising numbers of nuclear medicine centers. In this study, we estimated the radiation exposure to the occupational workers with pocket dosimeters during handling of the α-emitter 213Bi, used for targeted α-therapy of neuroendocrine tumor and castration-resistant prostate cancer patients. The dose rates from patients at different distances and time points after injection of the therapy were also evaluated. Methods: This prospective study was done in the Department of Nuclear Medicine at Fortis Memorial Research Institute, Gurgaon, India. Twelve patients with neuroendocrine tumors or castration-resistant prostate cancer were enrolled to receive 213Bi-DOTATOC or 213Bi-prostate-specific membrane antigen therapy, respectively. Each patient received 2-3 intravenous injections of 213Bi-peptide, 266-362 MBq (7.2-9.8 mCi) in a single cycle over 2-3 d. The radiation exposure to nuclear medicine personnel at the chest and extremity levels was assessed for tasks such as elution, dispensing, injecting, and collecting blood samples. Radiation levels were measured at distances of 1 cm and 1 m from patients immediately after, and at 1, 2, and 4 h after, the administration of 213Bi-peptide. Results: The external dose incurred at the chest level by radiopharmacists during synthesis, by physicians during injection, by technologists during imaging, and by nurses during sample collection was 2-7 µSv/procedure. The extremity dose was 1-14 µSv/procedure. The dose rate at 1 m from patients immediately after 213Bi-radiopharmaceutical injection was 0.02-0.03 µSv/MBq⋅h. Conclusion: The external radiation doses received by occupational workers involved in various procedures were far below the limit prescribed by the regulatory authority (20 mSv/y).

Impact of meibomian gland width on successful contact lens use.

PURPOSE: To evaluate meibomian gland (MG) width and determine its impact on successful contact lens (CL) use and ocular health. METHODS: A five-site study was conducted by recruiting 18- to 45-year-old subjects who had dropped out of CLs because of discomfort. CL dropouts were compared to age- and sex-matched successful CL wearers. Right eyes were evaluated for tear break-up time, tear meniscus height, MG expressibility, meibum quality, and meibography. Central MG widths were evaluated with a custom MATLAB program. RESULTS: CL dropouts (n = 56) and successful CL (n = 56) wearers had similar grades for upper (p = 1.0) and lower (p = 0.22) MG atrophy, upper (p = 0.07) and lower (p = 0.89) MG tortuosity, and upper (p = 0.92) and lower (p = 0.97) MG widths. Upper eyelid MG widths were narrower than lower eyelid MG widths (p = 0.03). Upper and lower MG tortuosity (p < 0.001) and widths (p = 0.03) were associated, but not atrophy (p = 0.42). Lower eyelid MG widths were associated with MG expressibility (p = 0.01), but MG widths were not with any other factors. CONCLUSIONS: Successful CL wear does not appear to be clinically influenced by MG width or other measures of MG structural integrity. Lower eyelid MGs were wider than upper eyelid MGs and narrower lower eyelid MGs were associated with worse MG expressibility, suggesting that narrower MGs may produce abnormal meibum. Data also suggests that MG factors of both eyelids should be evaluated in practice.

Clinical factors associated with contact lens dropout.

PURPOSE: Contact lens (CL) dropout is estimated to be approximately equal to the number of new wearers per year, resulting in virtually no growth in the global CL market. The purpose of this study was to determine ocular and CL factors associated with CL dropout. METHODS: This five-site study recruited subjects 18-45 years of age who had ceased CL wear within the past 6-12 months due to discomfort. Dropout subjects were compared to age- and sex-matched currently successful CL wearers. Each subject was administered a symptoms survey and a study-specific survey that queried general CL history and compliance. Clinical testing included non-invasive tear break-up time, tear meniscus height, blepharitis assessment, meibum quality and expression, and meibography. RESULTS: A total of 56 matched-pairs were recruited. Dry eye was found to significantly increase a subject's odds of dropping out of CLs. The odds of dropping out of CLs was also significantly increased with each worsening grade of upper or lower eyelid meibomian gland (MG) plugging, upper eyelid meibum quality, and upper eyelid MG tortuosity. No other factors analyzed increased a subject's odds of dropping out of CLs. CONCLUSIONS: CL dropout may be precipitated by underlying dry eye symptoms, though most dry eye signs, with the exception of MG structure and function, had minimal predictive value for CL dropout. Nevertheless, evidence suggests that practitioners should screen for and educate CL patients about the importance of maintaining healthy MGs, which may potentially allow them to maintain comfortable CL use and increase their CL longevity.

Performance evaluation of delefilcon a water gradient daily disposable contact lenses in first-time contact lens wearers.

PURPOSE: To evaluate the tolerability of and subject and investigator satisfaction with delefilcon A (DAILIES TOTAL1®) daily disposable contact lenses in first-time contact lens wearers. METHODS: This European multicenter, open-label, single-arm, two-week trial enrolled first-time contact lens wearers and fitted them with delefilcon A contact lenses. Assessments were made at dispensing and at Weeks 1 and 2. Subject-reported outcomes included comfort, quality of vision, convenience, and intent to purchase, which were ranked by agreement responses. Investigator-reported outcomes included slit-lamp biomicroscopy findings and lens fit satisfaction. RESULTS: Ninety-two subjects were included in the per protocol dataset. Mean scores at Weeks 1 and 2 for subject-reported quality of vision and ocular comfort were significantly higher with delefilcon A contact lenses than with the subjects' habitual spectacles during the day, at the end of the day, and overall (all p ≤ 0.02). Ninety-one percent of subjects reported that their study lenses were more comfortable than expected, 98% agreed that they were convenient to use, and 92% were interested in purchasing the lenses (all p < 0.001). Investigators reported that study lenses had an acceptable fit in at least 97% of subjects. CONCLUSIONS: Practitioners can expect favorable outcomes when transitioning first-time contact lens wearers from spectacles to delefilcon A daily disposable contact lenses.

A novel in-vitro method for assessing contact lens surface dewetting: Non-invasive keratograph dry-up time (NIK-DUT).

PURPOSE: This study was designed to develop a novel technique called non-invasive keratograph dry-up time (NIK-DUT), which used an adapted corneal topographer, to analyse in-vitro contact lens surface dewetting and the effects of combinations of lenses and lens care solutions on dewetting. METHODS: Variables were assessed to optimise sensitivity and reproducibility. To validate the method, in-vitro dewetting of silicone hydrogel contact lenses (balafilcon A, comfilcon A, lotrafilcon A, lotrafilcon B and senofilcon A) was tested. All lens types were soaked in OPTI-FREE® PureMoist® Multipurpose Disinfecting Solution (OFPM) and Sensitive Eyes® Saline Solution. The mean NIK-DUT, defined as drying of 25% of the placido ring measurement segments (NIK-DUT_S25), was calculated for each lens/lens solution combination and a visual map constructed representing the time and location of the dry-up event. RESULTS: Optimal conditions for NIK-DUT measurement included mounting onto a glass stage with a surface geometry of r=8.5mm, e=0, and measuring with high intensity red or white illumination. This method detected significant differences in contact lens dewetting with different lens soaking solutions. NIK-DUT_S25 for all lenses was longer when pre-soaked in OFPM versus saline. Visual analysis showed that dewetting of contact lenses was not uniform across surfaces and differed between test solutions. CONCLUSIONS: NIK-DUT is suitable for detecting differences in dewetting among various contact lenses and lens-care combinations. NIK-DUT can quantify the dewetting of large areas of lens surfaces with little subjective influence. Lens care solutions containing surface-active wetting agents were found to delay surface dewetting of silicone hydrogel lenses.

Radiosynthesis of clinical doses of 68Ga-DOTATATE (GalioMedix™) and validation of organic-matrix-based 68Ge/68Ga generators.

INTRODUCTION: 68Ga-DOTATATE is a radiolabeled peptide-based agonist that targets somatostatin receptors overexpressed in neuroendocrine tumors. Here, we present our results on validation of organic matrix 68Ge/68Ga generators (ITG GmbH) applied for radiosynthesis of the clinical doses of 68Ga-DOTATATE (GalioMedixTM). METHODS: The clinical grade of DOTATATE (25 µg±5 µg) compounded in 1 M NaOAc at pH=5.5 was labeled manually with 514±218 MBq (13.89±5.9 mCi) of 68Ga eluate in 0.05 N HCl at 95°C for 10 min. The radiochemical purity of the final dose was validated using radio-TLC. The quality control of clinical doses included tests of their osmolarity, endotoxin level, radionuclide identity, filter integrity, pH, sterility and 68Ge breakthrough. RESULTS: The final dose of 272±126 MBq (7.35±3.4 mCi) of 68Ga-DOTATATE was produced with a radiochemical yield (RCY) of 99%±1%. The total time required for completion of radiolabeling and quality control averaged approximately 35 min. This resulted in delivery of 50%±7% of 68Ga-DOTATATE at the time of calibration (not decay corrected). CONCLUSIONS: 68Ga eluted from the generator was directly applied for labeling of DOTA-peptide with no additional pre-concentration or pre-purification of isotope. The low acidity of 68Ga eluate allows for facile synthesis of clinical doses with radiochemical and radionuclide purity higher than 98% and average activity of 272±126 MBq (7.3±3 mCi). There is no need for post-labeling C18 Sep-Pak purification of final doses of radiotracer. Advances in knowledge and implications for patient care. The clinical interest in validation of 68Galabeled agents has increased in the past years due to availability of generators from different vendors (Eckert-Ziegler, ITG, iThemba), favorable approach of U.S. FDA agency to initiate clinical trials, and collaboration of U.S. centers with leading EU clinical sites. The list of 68Ga-labeled tracers evaluated in clinical studies should growth because of the sensitivity of PET technique, the simplicity of the shakebake approach for the dose preparation and reliability of 68Ge/68Ga generators. Our studies have confirmed the reproducible elution profile, and high reliability of ITG GmbH generators required for routine doses preparation according to FDA recommendations.

Associations with Meibomian Gland Atrophy in Daily Contact Lens Wearers.

PURPOSE: To determine associations for contact lenses (CLs) and meibomian gland atrophy in a matched-pair study. METHODS: Contact lens wearers (case) and age- and sex-matched non-contact lens (NCL) wearers with no history of CL use (control) were recruited for a multicenter study. All subjects were administered the Ocular Surface Disease Index questionnaire and a comprehensive battery of clinical tests (e.g., tear breakup time, bulbar and limbal redness, meibography, etc.) were performed. Upper and lower eyelid meibomian gland atrophy were graded with both digital meibography (percent gland atrophy) and visual meiboscore methods. Conditional logistic regression analyses were then used to determine relationships among CL use, meibomian gland atrophy, and ocular surface signs and symptoms. RESULTS: A total of 70 matched pairs were analyzed. The mean (± SD) age of the CL group was 30.6 (± 12.4) years, and that of the NCL group was 30.1 (± 12.2) years. The subjects were 63% female. The association between CL wear and meiboscore was not significant univariately, but the best-fitting multivariate regression model showed that higher meiboscores were associated with being a CL wearer (odds ratio [OR], 2.45) in a model that included eyelid margin erythema (OR, 0.25) and lissamine green staining (OR, 1.25). Percent gland atrophy was not associated with CL wear in regression analysis (p = 0.31). CONCLUSIONS: This study determined inconclusive associations with CLs and meibomian gland atrophy. This study also provided a comprehensive assessment of differences between CL and NCL wearers.

Anti-CD33-antibodies labelled with the alpha-emitter Bismuth-213 kill CD33-positive acute myeloid leukaemia cells specifically by activation of caspases and break radio- and chemoresistance by inhibition of the anti-apoptotic proteins X-linked inhibitor of apoptosis protein and B-cell lymphoma-extra large.

AIM: The emerging interest in radioimmunotherapies employing alpha-emitters for cancer treatment like high risk-leukaemia leads to the question of how these radionuclides exhibit their cytotoxicity. To clarify the molecular mechanisms of cell death induction, we investigated the molecular effects of the alpha-emitter Bismuth-213 (Bi-213) bound to a monoclonal anti-CD33-antibody ([Bi-213]anti-CD33) on the cell cycle and on apoptosis induction in sensitive as well as in beta- and gamma-radiation-resistant CD33-positive acute myeloid leukaemia (AML) cells. METHODS: The cytotoxic potential of the radioimmunoconjugate [Bi-213]anti-CD33 was analysed in the CD33-expressing human AML cell line HL-60 and in radiation- and chemoresistant HL-60-derived cell lines. Cell cycle and apoptosis induction analyses were performed via flow cytometry. Activation of apoptosis pathways was determined by immunodetection. RESULTS: [Bi-213]anti-CD33 induced apoptotic cell death in CD33-positive AML cells specifically. Molecular analyses revealed that the intrinsic mitochondrial pathway of apoptosis was activated resulting in caspase-9 activation. In the apoptotic executioner cascade caspase-3 was activated and its substrate poly (ADP-ribose) polymerase (PARP) was cleaved. Notably, [Bi-213]anti-CD33 overcame radio- and chemoresistance by reversing deficient activation of apoptosis pathways in resistant CD33-positive AML cells and by the downregulation of inhibitors of apoptosis B-cell lymphoma-extra large (Bcl-xL) and X-linked inhibitor of apoptosis protein (XIAP) involved in leukaemia resistance. CONCLUSION: [Bi-213]anti-CD33 exhibits its cytotoxic effects specifically in CD33-expressing AML cells via induction of the intrinsic, mitochondrial pathway of apoptosis. The abrogation of chemo- and radioresistances and the reactivation of apoptotic pathways seem to be promising for the treatment of patients with so far untreatable resistant AML and underline the importance of this emerging therapeutic approach of targeted alpha-therapies.