Test-Retest Reliability of Intraocular Pressure Measurements With Office-Based Versus Home-Based Rebound Tonometers.

PRCIS: Intraocular pressure (IOP) measurements obtained with the HOME2 rebound tonometer are interchangeable with measurements obtained using the office-based IC100 and IC200 rebound tonometers, making characterization of circadian IOP achievable with no inter-device sources of variability. OBJECTIVE: To evaluate test-retest reliability between IOP measurements obtained with a home rebound tonometer operated by patients and those obtained with office rebound tonometers operated by experienced clinical staff. METHODS: After training and practice with a home rebound tonometer (iCare HOME2) in a randomly selected eye, patients with established or suspected open angle glaucoma underwent IOP measurement in the fellow eye as follows in randomized order: 3 good quality measurements with the iCare IC100 operated by experienced clinical staff, 3 good quality measurements with the iCare IC200 operated by experienced clinical staff, and 3 good quality measurements with the HOME2 operated by the patient. The Shrout-Fleisch intraclass correlation coefficient (ICC; 2,1) was the measure of reliability utilized based on the model using 2-way random effects, absolute agreement, and single measurement. RESULTS: Thirty eyes of 30 patients were evaluated. The Pearson correlation coefficient ( r ) for IOP measurements taken with the IC100 and HOME2 was 0.97, with the IC200 and HOME2 was 0.96, and with the IC100 and IC200 was 0.97. Test-retest reliability between HOME2 and IC100 (ICC: 0.90), HOME2 and IC200 (ICC: 0.92), and IC100 and IC200 (ICC: 0.94) all reflected excellent test-retest reliability. CONCLUSION: The test-retest reliability of IOP measurements taken by patients using the iCare HOME2 self-tonometer compared with IOP measurements taken by trained operators using the iCare IC100 and IC200 tonometers was uniformly excellent (ICCs all ≥0.9). These findings indicate that these three devices should be considered interchangeable for the clinical assessment of circadian IOP.

Iris Chafing Syndrome Secondary to Iridociliary Adhesions in a Patient with a Single-Piece Acrylic Intraocular Lens: Case Report.

Introduction: We present a unique case of iris chafing syndrome in a patient with a complex ophthalmologic history after successful placement of a single-piece in-the-bag intraocular lens (IOL) in an eye with healthy zonular support. Case Presentation: A patient with a previous history of multiple retinal surgeries presented with pain and elevated intraocular pressure (IOP) secondary to retained viscoelastic material in the anterior chamber. Following removal of the viscoelastic material in clinic, the patient underwent a combined cataract and glaucoma surgery. Subsequently, the patient developed signs and symptoms of iris chafing syndrome. Anterior segment imaging revealed the cause to be iridociliary adhesion causing an elimination of the sulcus space. Iris chafing syndrome was suspected when the patient presented post-operatively with changes in vision and anterior chamber inflammation. New iris transillumination defects present at the edge of the optic and haptic of the 1-piece lens helped confirm the diagnosis of UGH. Upon further investigation with gonioscopy, ultrasound biomicroscopy and anterior segment optical coherence tomography, it was determined that the patient had iridociliary adhesions. These adhesions eliminated the sulcus space, which resulted in iris chafing. The patient opted for conservative medical management. Best-corrected distance visual acuity remained stable at 20/100 and IOP remained well controlled. Conclusion: A complex ocular history of multiple retinal surgeries and retained viscoelastic material in the anterior chamber resulted in adhesions of the ciliary processes to the iris, leading to UGH syndrome in a patient with an otherwise unremarkable placement of a single-piece in-the-bag IOL.

Super-Resolution Ultrasound Localization Microscopy Using High-Frequency Ultrasound to Measure Ocular Perfusion Velocity in the Rat Eye.

Imaging of the ocular vasculature can provide new insights into the pathophysiology of ocular diseases. This study proposes a novel high-frequency super-resolution ultrasound localization microscopy (SRULM) technique and evaluates its ability to measure in vivo perfusion changes in the rat eye at elevated intraocular pressure (IOP). A 38.4 MHz center frequency linear array transducer on a VisualSonics Vevo F2 imaging platform was used to collect high frame rate (1 kHz) radiofrequency data of the posterior rat eye following systemic microbubble contrast injection. Following clutter and spatiotemporal non-local means filtering, individual microbubbles were localized and tracked. The microbubble tracks were accumulated over 10,000 frames to generate vascular images quantifying perfusion velocity and direction. Experiments were performed using physiologic relevant controlled flow states for algorithm validation and subsequently performed in vivo on the rat eye at 10 mm Hg IOP increments from 10 to 60 mm Hg. The posterior vasculature of the rat eye, including the ophthalmic artery, long posterior ciliary arteries and their branches, central retinal artery and retinal arterioles and venules were successfully visualized, and velocities quantified at each IOP level. Significant reductions in arterial flow were measured as IOP was elevated. High-frequency SRULM can be used to visualize and quantify the perfusion velocity of the rat eye in both the retrobulbar and intraocular vasculature simultaneously. The ability to detect ocular perfusion changes throughout the depth of the eye may help elucidate the role ischemia has in the pathophysiology of ocular diseases such as glaucoma.

Diabetic retinopathy screenings in West Virginia: an assessment of teleophthalmology implementation.

BACKGROUND: The prevalence of diabetes in the state of West Virginia (WV) is amongst the highest in the United States, making diabetic retinopathy (DR) and diabetic macular edema (DME) a major epidemiological concern within the state. Several challenges exist regarding access to eye care specialists for DR screening in this rural population. A statewide teleophthalmology program has been implemented. We analyzed real-world data acquired via these systems to explore the concordance between image findings and subsequent comprehensive eye exams and explore the impact of age on image gradeability and patient distance from the West Virginia University (WVU) Eye Institute on follow-up. METHODS: Nonmydriatic fundus images of diabetic eyes acquired at primary care clinics throughout WV were reviewed by retina specialists at the WVU Eye Institute. Analysis included the concordance between image interpretations and dilated examination findings, hemoglobin A1c (HbA1c) levels and DR presence, image gradeability and patient age, and distance from the WVU Eye Institute and follow-up compliance. RESULTS: From the 5,512 fundus images attempted, we found that 4,267 (77.41%) were deemed gradable.  Out of the 289 patients whose image results suggested DR, 152 patients (52.6%) followed up with comprehensive eye exams-finding 101 of these patients to truly have DR/DME and allowing us to determine a positive predictive value of 66.4%. Patients within the HbA1c range of 9.1-14.0% demonstrated significantly greater prevalence of DR/DME (p < 0.01).  We also found a statistically significant decrease in image gradeability with increased age.  When considering distance from the WVU Eye Institute, it was found that patients who resided within 25 miles demonstrated significantly greater compliance to follow-up (60% versus 43%, p < 0.01). CONCLUSIONS: The statewide implementation of a telemedicine program intended to tackle the growing burden of DR in WV appears to successfully bring concerning patient cases to the forefront of provider attention.  Teleophthalmology addresses the unique rural challenges of WV, but there is suboptimal compliance to essential follow-up with comprehensive eye exams. Obstacles remain to be addressed if these systems are to effectively improve outcomes in DR/DME patients and diabetic patients at risk of developing these sight-threatening pathologies.

Evaluation of machine learning algorithms for trabeculectomy outcome prediction in patients with glaucoma.

The purpose of this study was to evaluate the performance of machine learning algorithms to predict trabeculectomy surgical outcomes. Preoperative systemic, demographic and ocular data from consecutive trabeculectomy surgeries from a single academic institution between January 2014 and December 2018 were incorporated into models using random forest, support vector machine, artificial neural networks and multivariable logistic regression. Mean area under the receiver operating characteristic curve (AUC) and accuracy were used to evaluate the discrimination of each model to predict complete success of trabeculectomy surgery at 1 year. The top performing model was optimized using recursive feature selection and hyperparameter tuning. Calibration and net benefit of the final models were assessed. Among the 230 trabeculectomy surgeries performed on 184 patients, 104 (45.2%) were classified as complete success. Random forest was found to be the top performing model with an accuracy of 0.68 and AUC of 0.74 using 5-fold cross-validation to evaluate the final optimized model. These results provide evidence that machine learning models offer value in predicting trabeculectomy outcomes in patients with refractory glaucoma.

Comparative Outcomes of the Molteno3 and Baerveldt Glaucoma Implants.

PURPOSE: To compare outcomes between 2 nonvalved glaucoma drainage devices (GDDs) used to treat refractory glaucoma or in patients with neovascular/uveitic glaucoma likely to be poorly responsive to less aggressive therapies. DESIGN: Retrospective, nonrandomized, multicenter comparative study. PARTICIPANTS: A total of 117 eyes from 117 patients. METHODS: Retrospective chart review of patients who underwent implantation of the Baerveldt (BGI) (Abbott Medical Optics, Abbott Park, IL) or the Molteno3 glaucoma implant (MGI) (Molteno Ophthalmic Limited, Dunedin, New Zealand). Noninferiority of the MGI versus the BGI was tested with Cox and mixed-effects regression models. Interventions in each group were analyzed with chi-square tests. MAIN OUTCOME MEASURES: The primary outcome was time until device failure, defined as intraocular pressure (IOP) >21 mmHg or a reduction <20%, hypotony, reoperation for glaucoma, or loss of light perception. Secondary outcomes were intraoperative time, postoperative IOP, number of IOP-lowering medications, and visual acuity (VA). RESULTS: The MGI could not be deemed noninferior to the BGI with regard to time until device failure (hazard ratio [HR], 0.83; confidence interval [CI], 0.41-1.65). The MGI was noninferior to the BGI when comparing postoperative IOP, a difference of -0.40 mmHg (95% CI, -1.74-0.93). The MGI needed 2% fewer medications (ratio of 0.98, 95% CI, 0.79-1.22), but noninferiority could not be claimed. With regard to VA, the MGI's mean was 0.10 logarithm of the minimum angle of resolution (logMAR) higher (95% CI, -0.01-0.21), but noninferiority testing was again inconclusive. Intraoperative time for the MGI was 15.7 minutes shorter versus the 350 mm2 plate size BGI (P < 0.001) and 4.3 minutes shorter versus the 250 mm2 plate size BGI (P = 0.32). More patients in the MGI group needed secondary operative management (11%, P = 0.03). CONCLUSIONS: The MGI was noninferior to the BGI in lowering IOP. Differences in time until device failure, VA outcomes, and medication use were inconclusive. The MGI required more secondary operative interventions. The MGI required less time to implant than the BGI's 350 mm2 plate size implant. Overall, the use of both GDDs is justifiable to lower IOP when more conservative management has failed.

Mechanical Stability of Cryopreserved Split-Thickness Tectonic Corneal Grafts.

PURPOSE: To evaluate the influence of cryopreservation on the pressure-strain relationship of microkeratome dissected anterior stromal grafts (ASGs). METHODS: Partial thickness ASGs were created from 7 pairs of human corneas and randomized to immediate grafting or grafting after 3 months of cryopreservation at -80°C into a whole globe ex vivo corneal perforation model. High frequency ultrasound speckle tracking was used to calculate the cross-sectional axial and lateral strains in each graft at increasing intraocular pressure (IOP) from 5 to 30 mm Hg. The mean axial and lateral strains were compared between the paired groups. RESULTS: The mean axial and lateral strains were not significantly different between the cryopreserved and noncryopreserved ASGs. The mean lateral strains at 30 mm Hg in the noncryopreserved and cryopreserved grafts were 2.4% ± 2.1% and 1.4% ± 0.7% (P = 0.294), respectively. The mean axial strains at 30 mm Hg in the noncryopreserved and cryopreserved grafts were -7.8% ± 3.3% and -5.5% ± 3.0% (P = 0.198), respectively. A linear pressure-strain relationship was found for all grafts at physiologic IOP. CONCLUSIONS: ASGs cryopreserved at -80°C maintain their IOP-strain relationship compared with noncryopreserved ASGs at physiologic pressures, supporting the potential use of cryopreserved human corneal stroma for patch grafting procedures.

Corneal keloid presenting forty years after penetrating injury: Case report and literature review.

A 64-year-old Caucasian man had been diagnosed with presumed ocular surface squamous neoplasia in the left eye and started on topical interferon alpha 2b drops. When we saw him, he provided a history of penetrating corneal injury more than forty years before. Slit lamp examination revealed a large, elevated, opaque lesion involving the left cornea. High-definition anterior segment optical coherence tomography revealed a hyperreflective lesion involving the anterior stroma with a relatively normal overlying epithelium. Based on the clinical history, slit lamp, and anterior segment optical coherence tomography findings, a giant corneal keloid was suspected, and the interferon drops were discontinued. He subsequently underwent a penetrating keratoplasty, and histopathologic analysis was consistent with corneal keloid. Corneal keloids may be seen decades after the initial trauma, and anterior segment optical coherence tomography can be a useful tool in differentiating these tumor-like lesions from other neoplasia.

False-positive technetium-99m methylene diphosphonate bone scan activity in the orbit in a patient with a history of breast carcinoma.

Metastasis of breast carcinoma to the orbit is an uncommon entity and carries a poor prognosis. This case report presents false-positive technetium-99m methylene diphosphonate activity in the right orbit of a patient with a history of a primary breast neoplasm. Orbital computed tomography imaging was obtained to further characterize the radiotracer uptake identified on the bone scan and demonstrated diffuse right globe intraocular calcifications secondary to degenerative intraocular changes. A brief literature review of orbital metastasis from breast carcinoma and causes of intraocular calcification in the context of chronic vision loss are provided.

A case of indirect superior rectus pulled-in-two syndrome during superior oblique tenectomy.

A 67-year-old white man with a history of right orbital trauma and restrictive strabismus underwent right superior oblique tenectomy for superior oblique restriction. Bleeding was noted from the superior rectus intraoperatively, despite the fact that the muscle was neither exposed nor hooked for the procedure. Subsequent exploration of the muscle revealed a full-width tear across the superior rectus muscle approximately 5 mm posterior to its insertion. The remaining residual distal muscle was removed from the insertion and the proximal end of the torn superior rectus muscle was identified and reattached to the insertion. We postulate that shearing forces exerted by a taut superior oblique tendon were sufficient to tear the overlying superior rectus muscle.

Corneal Alterations Associated with Pseudoexfoliation Syndrome and Glaucoma: A Literature Review.

A systematic literature review was performed evaluating articles examining the effects of pseudoexfoliation syndrome (PEX) and glaucoma (PEXG) on the cornea with a focus on the corneal endothelium. We searched for articles relevant to pseudoexfoliation syndrome, pseudoexfoliation glaucoma and corneal endothelial cell counts using Pubmed, Google Scholar Database, Web of Science and Cochrane Library databases published prior to September of 2016. We then screened the references of these retrieved papers and performed a Web of Science cited reference search. Corneal characteristics analyzed included central corneal thickness (CCT), corneal nerve density, endothelial cell density (ECD), polymegathism, and pleomorphism. These parameters were compared in the following populations: control, PEX, PEXG, and primary open angle glaucoma (POAG). Over 30 observational studies were reviewed. Most studies showed a statistically significant lower ECD in PEX and PEXG populations compared to controls. Overall, PEX eyes had a non-statistically significant trend of lower ECDs compared to PEXG eyes. No consistent trends were found when analyzing differences in CCT amongst control, PEX and PEXG groups. For the few studies that looked at corneal nerve characteristics, the control groups were found to have statistically significantly greater nerve densities than PEX eyes, which had significantly greater densities than PEXG eyes. ECD and corneal nerve densities may be potential metrics for risk-stratifying patients with PEX and PEXG. Our literature review provided further evidence of the significant negative influence PEX has on the cornea, worsening as patients convert to PEXG.

Skew Deviation and Partial Ocular Tilt Reaction Due to Intratympanic Gentamicin Injection, with Review of the Literature.

Skew deviation is a rare side effect of intratympanic gentamicin injection for intractable Meniere's disease. When the skew deviation is accompanied by pathologic head tilt and ocular torsion, the result is an ocular tilt reaction (OTR). The authors report the case of a 56-year-old man with refractory Meniere's disease who developed binocular vertical diplopia following intratympanic gentamicin injection and was found to have skew deviation and a partial ocular tilt reaction. The authors also review the reported cases of skew deviation following intratympanic gentamicin and confirm this phenomenon, which has only rarely been reported in the literature.

Influence of Age on Ocular Biomechanical Properties in a Canine Glaucoma Model with ADAMTS10 Mutation.

Soft tissue often displays marked age-associated stiffening. This study aims to investigate how age affects scleral biomechanical properties in a canine glaucoma model with ADAMTS10 mutation, whose extracellular matrix is concomitantly influenced by the mutation and an increased mechanical load from an early age. Biomechanical data was acquired from ADAMTS10-mutant dogs (n = 10, 21 to 131 months) and normal dogs (n = 5, 69 to 113 months). Infusion testing was first performed in the whole globes to measure ocular rigidity. After infusion experiments, the corneas were immediately trephined to prepare scleral shells that were mounted on a pressurization chamber to measure strains in the posterior sclera using an inflation testing protocol. Dynamic viscoelastic mechanical testing was then performed on dissected posterior scleral strips and the data were combined with those reported earlier by our group from the same animal model (Palko et al, IOVS 2013). The association between age and scleral biomechanical properties was evaluated using multivariate linear regression. The relationships between scleral properties and the mean and last measured intraocular pressure (IOP) were also evaluated. Our results showed that age was positively associated with complex modulus (p<0.001) and negatively associated with loss tangent (p<0.001) in both the affected and the normal groups, suggesting an increased stiffness and decreased mechanical damping with age. The regression slopes were not different between the groups, although the complex modulus was significantly lower in the affected group (p = 0.041). The posterior circumferential tangential strain was negatively correlated with complex modulus (R = -0.744, p = 0.006) showing consistent mechanical evaluation between the testing methods. Normalized ocular rigidity was negatively correlated with the last IOP in the affected group (p = 0.003). Despite a mutation that affects the extracellular matrix and a chronic IOP elevation in the affected dogs, age-associated scleral stiffening and loss of mechanical damping were still prominent and had a similar rate of change as in the normal dogs.

Changes in posterior scleral collagen microstructure in canine eyes with an ADAMTS10 mutation.

PURPOSE: We aimed to characterize alterations in the posterior scleral collagen microstructure before detectable disease onset in a canine model of open-angle glaucoma caused by an ADAMTS10 mutation. METHODS: Collagen orientation, anisotropy degree (proportion of preferentially aligned collagen), and relative density were measured at 0.4 mm spatial resolution using synchrotron wide-angle X-ray scattering. For statistical evaluation of structure parameters, regional averages of the peripapillary and mid-posterior sclera were compared between ADAMTS10 mutant (affected) dogs (n = 3) and age-matched (carrier) controls (n = 3). RESULTS: No marked differences in the general pattern of preferential collagen fibril orientation were noted between the control and affected dogs. The peripapillary sclera of all specimens featured strongly aligned circumferential collagen ringing the optic nerve head. Collagen anisotropy was significantly reduced in the mid-posterior sclera of the affected dogs (carrier: 0.27±0.11; affected: 0.24±0.10; p = 0.032) but was not statistically significantly different in the peripapillary sclera (carrier: 0.46±0.15; affected: 0.45±0.17; p = 0.68). Collagen density was statistically significantly reduced in the affected dogs for the mid-posterior sclera (carrier: 28.1±9.14; affected: 18.3±5.12; p<0.0001) and the peripapillary sclera (carrier: 34.6±9.34; affected: 21.1±6.97; p = 0.0002). CONCLUSIONS: Significant alterations in the posterior scleral collagen microstructure are present before the onset of clinical glaucoma in ADAMTS10 mutant dogs. A reduction in fibrous collagen density is likely an important contributory factor in the previously reported mechanical weakening of the sclera in this model. Baseline scleral abnormalities have the potential to interact with intraocular pressure (IOP) elevations in determining the course of glaucoma progression in animal models of the disease, and potentially in human glaucoma.

Three-Dimensional Strains in Human Posterior Sclera Using Ultrasound Speckle Tracking.

Intraocular pressure (IOP) induced strains in the peripapillary sclera may play a role in glaucoma progression. Using inflation testing and ultrasound speckle tracking, the 3D strains in the peripapillary sclera were measured in nine human donor globes. Our results showed that the peripapillary sclera experienced through-thickness compression and meridional stretch during inflation, while minimal circumferential dilation was observed when IOP was increased from 10 to 19 mmHg. The maximum shear was primarily oriented in the through-thickness, meridional cross sections and had a magnitude slightly larger than the first principal strain. The tissue volume had minimal overall change, confirming near-incompressibility of the sclera. Substantial strain heterogeneity was present in the peripapillary region, with local high strain areas likely corresponding to structural heterogeneity caused by traversing blood vessels. These 3D strain characteristics provide new insights into the biomechanical responses of the peripapillary sclera during physiological increases of IOP. Future studies are needed to confirm these findings and investigate the role of these biomechanical characteristics in ocular diseases.

Spatially heterogeneous corneal mechanical responses before and after riboflavin-ultraviolet-A crosslinking.

PURPOSE: To determine the heterogeneous through-thickness strains in the cornea at physiologic intraocular pressures before and after corneal collagen crosslinking (CXL) using noninvasive ultrasound. SETTING: Department of Biomedical Engineering, Ohio State University, Columbus, Ohio, USA. DESIGN: Experimental study. METHODS: Sixteen paired canine corneoscleral shells were divided into 2 groups. The CXL group completed a standard CXL protocol using riboflavin-ultraviolet-A (UVA) irradiation. The control group was given an identical treatment except UVA irradiation. Ultrasound scans (at 55 MHz) of the cornea were obtained before and after treatment as the corneoscleral shell was inflated from 5 mm Hg to 45 mm Hg to calculate the distributive through-thickness strains in the cornea. The mean radial and tangential strains of the whole cornea layer, as well as those of the anterior, middle, and posterior thirds of the cornea, were compared before and after treatment in the control group and CXL group using linear mixed models with repeated measures. RESULTS: Significant reductions in tangential and radial strains occurred in the CXL group (P=.003 and P=.0025, respectively) but not the control group (P=.08 and P=.63, respectively). The anterior third had the smallest strains in all pretreated corneas (P<.001) and posttreated corneas (CXL group, P=.023; control group, P=.01). CONCLUSIONS: Ultrasound speckle tracking showed heterogeneous strain distributions through the cornea and confirmed that CXL results in a stiffer corneal response (ie, smaller strains during physiologic loadings). This technique may provide a clinical tool to quantify the biomechanical effects of CXL. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Biaxial mechanical testing of posterior sclera using high-resolution ultrasound speckle tracking for strain measurements.

This study aimed to characterize the mechanical responses of the sclera, the white outer coat of the eye, under equal-biaxial loading with unrestricted shear. An ultrasound speckle tracking technique was used to measure tissue deformation through sample thickness, expanding the capabilities of surface strain techniques. Eight porcine scleral samples were tested within 72 h postmortem. High resolution ultrasound scans of scleral cross-sections along the two loading axes were acquired at 25 consecutive biaxial load levels. An additional repeat of the biaxial loading cycle was performed to measure a third normal strain emulating a strain gage rosette for calculating the in-plane shear. The repeatability of the strain measurements during identical biaxial ramps was evaluated. A correlation-based ultrasound speckle tracking algorithm was used to compute the displacement field and determine the distributive strains in the sample cross-sections. A Fung type constitutive model including a shear term was used to determine the material constants of each individual specimen by fitting the model parameters to the experimental stress-strain data. A non-linear stress-strain response was observed in all samples. The meridian direction had significantly larger strains than that of the circumferential direction during equal-biaxial loadings (P's<0.05). The stiffness along the two directions was also significantly different (P=0.02) but highly correlated (R(2)=0.8). These results showed that the mechanical properties of the porcine sclera were nonlinear and anisotropic under biaxial loading. This work has also demonstrated the feasibility of using ultrasound speckle tracking for strain measurements during mechanical testing.

Biomechanical properties and correlation with collagen solubility profile in the posterior sclera of canine eyes with an ADAMTS10 mutation.

PURPOSE: We examined the biomechanical properties and correlation with the collagen solubility profile of the posterior sclera in a canine model of primary open-angle glaucoma caused by the G661R missense mutation in the ADAMTS10 gene. METHODS: Scleral strips from ADAMTS10-mutant (affected) dogs and age-matched controls were collected. Viscoelastic properties (i.e., complex modulus and tan[δ]) were measured using dynamic mechanical analysis (DMA) with a 0.15% sinusoidal strain at different frequencies superimposed upon different preloads. A tensile ramp was performed following DMA. The collagen solubility profile was examined using a colorimetric hydroxyproline assay to determine the amount of soluble and insoluble collagen. The viscoelastic properties were compared between groups using linear mixed models for repeated measures at different preloads and frequencies. The correlation between the biomechanical properties and collagen content were evaluated using Pearson correlations. RESULTS: Complex modulus and tan(δ) were significantly lower in the affected group (P < 0.001), and the differences were consistent at different preloads and frequencies. The B value from the tensile ramp test also was significantly lower in the affected group (P = 0.02). The insoluble collagen was significantly lower in the affected group (P < 0.05) and correlated positively with the complex modulus (R = 0.88, P < 0.005). CONCLUSIONS: An inherently weaker and biochemically distinct posterior sclera was observed in dogs with the G661R missense mutation in ADAMTS10 before clinical indications of optic nerve damage. It remains to be shown whether and how the altered scleral biomechanics may affect the rate of glaucoma progression following intraocular pressure elevation.

Dynamic testing of regional viscoelastic behavior of canine sclera.

Intraocular pressure (IOP) fluctuations have gained recent clinical interest and thus warrant an understanding of how the sclera responds to dynamic mechanical insults. The objective of this study was to characterize the regional dynamic viscoelastic properties of canine sclera under physiological cyclic loadings. Scleral strips were excised from the anterior, equatorial, and posterior sclera in ten canine eyes. The dimensions of each strip were measured using a high resolution ultrasound imaging system. The strips were tested in a humidity chamber at approximately 37 °C using a Rheometrics Systems Analyzer. A cyclic strain input (0.25%, 1 Hz) was applied to the strips, superimposed upon pre-stresses corresponding to an IOP of 15, 25, and 45 mmHg. The cyclic stress output was recorded and the dynamic properties were calculated based on linear viscoelasticity. Uni-axial tensile tests were also performed on the same samples and the results were compared to those reported for human eyes. The results showed that the sclera's resistance to dynamic loading increased significantly while the damping capability decreased significantly with increasing pre-stresses for all regions of sclera (P < 0.001). Anterior sclera appeared to have a significantly higher damping capability than equatorial and posterior sclera (P = 0.003 and 0.018, respectively). The secant modulus from uni-axial tensile tests showed a decreasing trend from anterior to posterior sclera, displaying a similar pattern as in the human eye. In conclusion, all scleral regions in the canine eyes exhibited an increased ability to resist and a decreased ability to dampen cyclic stress insults at increasing pre-stress (i.e., increasing steady-state IOP). The regional variation of the dynamic properties differed from those of uni-axial tensile tests. Dynamic testing may provide useful information to better understand the mechanical behavior of the sclera in response to dynamic IOP.

The effects of decorin and HGF-primed vocal fold fibroblasts in vitro and ex vivo in a porcine model of vocal fold scarring.

OBJECTIVES: Vocal fold injury can be irreversible, leading to vocal fold scarring, with permanent functional effects and no optimal treatment. A porcine model of vocal fold scarring was used to test effects of decorin and primed vocal fold fibroblasts in vitro using a cell migration assay and immunoblotting, and by using functional measurements of porcine larynges and excised porcine vocal folds. METHODS: In vitro: primary pig vocal fold fibroblasts (PVFFs) were subjected to cell migration assays (scratch) and treated with decorin 20 µg/mL, hepatocyte growth factor (HGF) 200 ng/mL, epidermal growth factor (EGF) 1 nM, or transforming growth factor-ß1 10 ng/mL. Cells also underwent decorin dose response testing. Scratch assays were analyzed in MetaMorph® Imaging; cell lysates were processed for MMP-8 and type I collagen content. Eleven pigs underwent unilateral vocal fold stripping procedures. At day 3 postoperatively, subjects underwent superficial injection into the affected vocal fold either with decorin 20 µg/mL or 1 × 10(6) HGF-primed fibroblasts. Larynges were harvested and either used for ex vivo laryngeal testing or for rheological testing. RESULTS: Scratch assay indicated significantly reduced cell migration in PVFFs treated with decorin or HGF. MMP-8 production was increased (P <0.01) and collagen was decreased in cells treated with decorin at increasing doses. Viscoelastic measurements suggested somewhat increased stiffness for decorin treated samples. Ex vivo aerodynamic testing suggested improved vocal efficiency scores in decorin-treated larynges. CONCLUSIONS: Decorin has a noticeable effect on PVFF migration in vitro and appears to increase vocal fold stiffness but either does not change or slightly increases vocal efficiency.