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Purpose: To determine the effect of discontinuing chronic topical immune modulating (IM) treatment on Schirmer tear test (STT) values in dogs with dry eye disease (DED). Methods: Serial measurements of STTs from 14 dogs (16 eyes) previously diagnosed with DED were obtained before and after discontinuation of topical IM agents. Dogs with moderate to severe DED that had been well controlled with a topical IM treatment were included. After initial assessment topical IM treatment was discontinued, but topical lubricant was continued, and STT values were obtained sequentially. A mixed-effects regression model was used to evaluate the effects of age, gender, breed, clinical score, frequency of treatment, baseline STT value, and drug type on final STT values after IM withdrawal. P < 0.05 was considered statistically significant. Results: During the follow-up period after the IM treatment had been discontinued (136 ± 29 days), 50% of the eyes (n = 8) exhibited STT values that never decreased to <10 mm/min. In the other 50% (n = 8), STT values decreased from 15.9 ± 4.7 mm/min to 6.1 ± 0.9 mm/min. In this group, the time it took to decrease the STT to <10 mm/min was 21.1 ± 9.5 days. Severe clinical signs of DED and low baseline STT pre-IM treatment significantly affected STT post-IM treatment withdrawal (P < 0.05). Conclusions: The duration that a residual effect of topical IM treatment persists needs to be taken into consideration when studies are designed utilizing dogs with previous IM treatment for DED.

Continuous monitoring of intraocular pressure, particularly during sleep, remains a grand challenge in glaucoma care. Here we introduce a class of smart soft contact lenses, enabling the continuous 24-hour monitoring of intraocular pressure, even during sleep. Uniquely, the smart soft contact lenses are built upon various commercial brands of soft contact lenses without altering their intrinsic properties such as lens power, biocompatibility, softness, transparency, wettability, oxygen transmissibility, and overnight wearability. We show that the smart soft contact lenses can seamlessly fit across different corneal curvatures and thicknesses in human eyes and therefore accurately measure absolute intraocular pressure under ambulatory conditions. We perform a comprehensive set of in vivo evaluations in rabbit, dog, and human eyes from normal to hypertension to confirm the superior measurement accuracy, within-subject repeatability, and user comfort of the smart soft contact lenses beyond current wearable ocular tonometers. We envision that the smart soft contact lenses will be effective in glaucoma care.

Continuous monitoring of intraocular pressure, particularly during sleep, remains a grand challenge in glaucoma care. Here we introduce a class of smart soft contact lenses, enabling the continuous 24-hour monitoring of intraocular pressure, even during sleep. Uniquely, the smart soft contact lenses are built upon various commercial brands of soft contact lenses without altering their intrinsic properties such as lens power, biocompatibility, softness, transparency, wettability, oxygen transmissibility, and overnight wearability. We show that the smart soft contact lenses can seamlessly fit across different corneal curvatures and thicknesses in human eyes and therefore accurately measure absolute intraocular pressure under ambulatory conditions. We perform a comprehensive set of in vivo evaluations in rabbit, dog, and human eyes from normal to hypertension to confirm the superior measurement accuracy, within-subject repeatability, and user comfort of the smart soft contact lenses beyond current wearable ocular tonometers. We envision that the smart soft contact lenses will be effective in glaucoma care.

Continuous monitoring of intraocular pressure, particularly during sleep, remains a grand challenge in glaucoma care. Here we introduce a class of smart soft contact lenses, enabling the continuous 24-hour monitoring of intraocular pressure, even during sleep. Uniquely, the smart soft contact lenses are built upon various commercial brands of soft contact lenses without altering their intrinsic properties such as lens power, biocompatibility, softness, transparency, wettability, oxygen transmissibility, and overnight wearability. We show that the smart soft contact lenses can seamlessly fit across different corneal curvatures and thicknesses in human eyes and therefore accurately measure absolute intraocular pressure under ambulatory conditions. We perform a comprehensive set of in vivo evaluations in rabbit, dog, and human eyes from normal to hypertension to confirm the superior measurement accuracy, within-subject repeatability, and user comfort of the smart soft contact lenses beyond current wearable ocular tonometers. We envision that the smart soft contact lenses will be effective in glaucoma care.

Continuous monitoring of intraocular pressure, particularly during sleep, remains a grand challenge in glaucoma care. Here we introduce a class of smart soft contact lenses, enabling the continuous 24-hour monitoring of intraocular pressure, even during sleep. Uniquely, the smart soft contact lenses are built upon various commercial brands of soft contact lenses without altering their intrinsic properties such as lens power, biocompatibility, softness, transparency, wettability, oxygen transmissibility, and overnight wearability. We show that the smart soft contact lenses can seamlessly fit across different corneal curvatures and thicknesses in human eyes and therefore accurately measure absolute intraocular pressure under ambulatory conditions. We perform a comprehensive set of in vivo evaluations in rabbit, dog, and human eyes from normal to hypertension to confirm the superior measurement accuracy, within-subject repeatability, and user comfort of the smart soft contact lenses beyond current wearable ocular tonometers. We envision that the smart soft contact lenses will be effective in glaucoma care.

Continuous monitoring of intraocular pressure, particularly during sleep, remains a grand challenge in glaucoma care. Here we introduce a class of smart soft contact lenses, enabling the continuous 24-hour monitoring of intraocular pressure, even during sleep. Uniquely, the smart soft contact lenses are built upon various commercial brands of soft contact lenses without altering their intrinsic properties such as lens power, biocompatibility, softness, transparency, wettability, oxygen transmissibility, and overnight wearability. We show that the smart soft contact lenses can seamlessly fit across different corneal curvatures and thicknesses in human eyes and therefore accurately measure absolute intraocular pressure under ambulatory conditions. We perform a comprehensive set of in vivo evaluations in rabbit, dog, and human eyes from normal to hypertension to confirm the superior measurement accuracy, within-subject repeatability, and user comfort of the smart soft contact lenses beyond current wearable ocular tonometers. We envision that the smart soft contact lenses will be effective in glaucoma care.

Re-epithelialization of wounds is a critical element of wound closure. Growth factors have been used in combination with conventional wound management to promote closure, but the method of delivery has been limited to the topical application of ointment formulations. Cytoactive factors delivered in this way have short resident times in wounds and have met with limited success. Here, we demonstrate that methods used to covalently immobilize proteins on synthetic materials can be extended to immobilize cytoactive factors such as the epidermal growth factor (EGF) onto the wound beds of genetically diabetic mice that exhibit impaired healing. Full-thickness splinted excisional wounds were created in diabetic (db/db) mice with a well-defined silicone splint to limit wound contracture. Wound surfaces were treated with a reducing agent to expose sulfhydryl groups and subsequently treated with EGF modified with a heterobifunctional crosslinker. This allowed for the covalent immobilization of the EGF to the wound surface. The conjugation chemistry was validated in vitro and in vivo. In a separate group of mice, wounds were topically treated twice daily with soluble EGF. The mice were evaluated over 11 days for wound closure. This covalent immobilization strategy resulted in EGF being retained on the wound surface for 2 days and significantly increased epithelial wound closure by 20% compared to wounds treated with topical EGF or topical vehicle. Covalent immobilization was not only therapeutically effective but also delivered a markedly reduced load of growth factor to the wound surface compared to topical application (when only 180 ng of EGF was immobilized onto the wound surface in comparison with 7200 ng of topically applied EGF over a period of 11 days). No adverse effects were observed in treated wounds. Results obtained provide proof of concept for the effectiveness of covalent immobilization in the treatment of dysregulated wounds. The covalent immobilization of cytoa

Topical application of platelet-derived growth factor-BB (PDGF-BB) is considered to accelerate tissue repair of impaired chronic wounds. However, the vast literature is plagued with conflicting reports of its efficacy in animal models and this is often influenced by a wide array of experimental variables making it difficult to compare the results across the studies. To mitigate the confounding variables that influence the efficacy of topically applied PDGF-BB, we used a controlled full thickness splinted excisional wound model in db/db mice (type 2 diabetic mouse model) for our investigations. A carefully-defined silicone-splinted wound model, with reduced wound contraction, controlled splint and bandage maintenance, allowing for healing primarily by reepithelialization was employed. Two splinted 8 mm dorsal full thickness wounds were made in db/db mice. Wounds were topically treated once daily with either 3 µg PDGF-BB in 30 µl of 5% PEG-PBS vehicle or an equal volume of vehicle for 10 days. Body weights, wound contraction, wound closure, reepithelialization, collagen content, and wound bed inflammation were evaluated clinically and histopathologically. The bioactivity of PDGF-BB was confirmed by in vitro proliferation assay. PDGF-BB, although bioactive in vitro, failed to accelerate wound healing in vivo in the db/db mice using the splinted wound model. Considering that the predominant mechanism of wound healing in humans is by re-epithelialization, the most appropriate model for evaluating therapeutics is one that uses splints to prevent excessive wound contraction. Here, we report that PDGF-BB does not promote wound closure by re-epithelialization in a murine splinted wound model. Our results highlight that the effects of cytoactive factors reported in vivo ought to be carefully interpreted with critical consideration of the wound model used.

ObjectiveTo evaluate repeatability and reproducibility of tear osmolarity measured using the TearLab™ osmometer in normal dogs and to assess its diagnostic potential in dogs with keratoconjunctivitis sicca (KCS).Animals studiedBeagle dogs; six normal and five with KCS.ProceduresTear osmolarity and Schirmer tear test-1 (STT-1) values were obtained at various times. Normal dogs were assessed for diurnal variation and repeatability and reproducibility of measurements. Dogs with KCS were evaluated before and after 5 months' topical twice-daily therapy with 2% cyclosporine.ResultsMean ± SD tear osmolarity (mOsm/L) was significantly higher in normal dogs (337.4 ± 16.2) than in dogs with KCS before therapy (306.2 ± 18.0; P < 0.0001), but not following therapy with 2% cyclosporine (330.5 ± 13.7; P = 1.00). Osmolarity readings lower than 325.5 mOsm/L were suggestive of KCS (84.8% sensitivity and 87.1% specificity). In normal dogs, tear osmolarity readings were stable during the daytime (P = 0.99). Repeated measurements revealed high variability and typically poor-to-moderate repeatability and reproducibility, although this was improved by taking three successive measurements at each session. Considering combined data from all dogs, a positive correlation existed between STT-1 and tear osmolarity measurements (Pearson's correlation test, P = 0.04, r = 0.62).ConclusionsCanine tear osmolarity as determined by TearLab™ osmometer was variable, required multiple readings to be informative, and differed from values reported for humans. Dogs with KCS had a lower tear osmolarity than did normal dogs, and this increased following cyclosporine therapy.

The selection of oxide materials for catalyzing the oxygen evolution reaction in acid-based electrolyzers must be guided by the proper balance between activity, stability and conductivity-a challenging mission of great importance for delivering affordable and environmentally friendly hydrogen. Here we report that the highly conductive nanoporous architecture of an iridium oxide shell on a metallic iridium core, formed through the fast dealloying of osmium from an Ir25Os75 alloy, exhibits an exceptional balance between oxygen evolution activity and stability as quantified by the activity-stability factor. On the basis of this metric, the nanoporous Ir/IrO2 morphology of dealloyed Ir25Os75 shows a factor of ~30 improvement in activity-stability factor relative to conventional iridium-based oxide materials, and an ~8 times improvement over dealloyed Ir25Os75 nanoparticles due to optimized stability and conductivity, respectively. We propose that the activity-stability factor is a key "metric" for determining the technological relevance of oxide-based anodic water electrolyzer catalysts.

ObjectiveTo evaluate repeatability and reproducibility of tear osmolarity measured using the TearLab™ osmometer in normal dogs and to assess its diagnostic potential in dogs with keratoconjunctivitis sicca (KCS).Animals studiedBeagle dogs; six normal and five with KCS.ProceduresTear osmolarity and Schirmer tear test-1 (STT-1) values were obtained at various times. Normal dogs were assessed for diurnal variation and repeatability and reproducibility of measurements. Dogs with KCS were evaluated before and after 5 months' topical twice-daily therapy with 2% cyclosporine.ResultsMean ± SD tear osmolarity (mOsm/L) was significantly higher in normal dogs (337.4 ± 16.2) than in dogs with KCS before therapy (306.2 ± 18.0; P < 0.0001), but not following therapy with 2% cyclosporine (330.5 ± 13.7; P = 1.00). Osmolarity readings lower than 325.5 mOsm/L were suggestive of KCS (84.8% sensitivity and 87.1% specificity). In normal dogs, tear osmolarity readings were stable during the daytime (P = 0.99). Repeated measurements revealed high variability and typically poor-to-moderate repeatability and reproducibility, although this was improved by taking three successive measurements at each session. Considering combined data from all dogs, a positive correlation existed between STT-1 and tear osmolarity measurements (Pearson's correlation test, P = 0.04, r = 0.62).ConclusionsCanine tear osmolarity as determined by TearLab™ osmometer was variable, required multiple readings to be informative, and differed from values reported for humans. Dogs with KCS had a lower tear osmolarity than did normal dogs, and this increased following cyclosporine therapy.

The selection of oxide materials for catalyzing the oxygen evolution reaction in acid-based electrolyzers must be guided by the proper balance between activity, stability and conductivity-a challenging mission of great importance for delivering affordable and environmentally friendly hydrogen. Here we report that the highly conductive nanoporous architecture of an iridium oxide shell on a metallic iridium core, formed through the fast dealloying of osmium from an Ir25Os75 alloy, exhibits an exceptional balance between oxygen evolution activity and stability as quantified by the activity-stability factor. On the basis of this metric, the nanoporous Ir/IrO2 morphology of dealloyed Ir25Os75 shows a factor of ~30 improvement in activity-stability factor relative to conventional iridium-based oxide materials, and an ~8 times improvement over dealloyed Ir25Os75 nanoparticles due to optimized stability and conductivity, respectively. We propose that the activity-stability factor is a key "metric" for determining the technological relevance of oxide-based anodic water electrolyzer catalysts.

ObjectiveTo describe the lacrimal system of snakes using contrast micro-computed tomography (micro-CT) with 3-dimensional reconstruction, fluorescein passage ('Jones') testing, histology, and gross dissection.Animals studiedOne royal python and 19 snake cadavers representing 10 species.ProceduresDirect observation following injection of fluorescein into the subspectacular space, micro-CT following injection of three contrast agents into the subspectacular space, gross dissection following injection of latex into the subspectacular space, and histopathology.ResultsInjection of fluorescein confirmed patency, but not course of the lacrimal duct. Barium enabled clear visualization of the lacrimal duct, whereas two iodinated contrast agents proved inadequate. Collectively, micro-CT, anatomic dissections, and histology suggest tears are produced by a single, large, serous, retrobulbar gland, released into the subspectacular space via several ductules, and drained through a single punctum originating in the ventronasal subspectacular space, and the lacrimal duct, which takes one of three routes of variable tortuosity before opening into the oral cavity in close association with the opening of the duct of the vomeronasal organ.ConclusionsThe ophidian lacrimal duct has a generally tortuous course, and the details of its anatomy are species-variable. The tortuous course of the duct likely predisposes snakes to duct occlusion and must be considered when planning medical and surgical interventions in snakes with pseudobuphthalmos and subspectacular abscessation.

ObjectiveTo describe the lacrimal system of snakes using contrast micro-computed tomography (micro-CT) with 3-dimensional reconstruction, fluorescein passage ('Jones') testing, histology, and gross dissection.Animals studiedOne royal python and 19 snake cadavers representing 10 species.ProceduresDirect observation following injection of fluorescein into the subspectacular space, micro-CT following injection of three contrast agents into the subspectacular space, gross dissection following injection of latex into the subspectacular space, and histopathology.ResultsInjection of fluorescein confirmed patency, but not course of the lacrimal duct. Barium enabled clear visualization of the lacrimal duct, whereas two iodinated contrast agents proved inadequate. Collectively, micro-CT, anatomic dissections, and histology suggest tears are produced by a single, large, serous, retrobulbar gland, released into the subspectacular space via several ductules, and drained through a single punctum originating in the ventronasal subspectacular space, and the lacrimal duct, which takes one of three routes of variable tortuosity before opening into the oral cavity in close association with the opening of the duct of the vomeronasal organ.ConclusionsThe ophidian lacrimal duct has a generally tortuous course, and the details of its anatomy are species-variable. The tortuous course of the duct likely predisposes snakes to duct occlusion and must be considered when planning medical and surgical interventions in snakes with pseudobuphthalmos and subspectacular abscessation.