Browsing by Author "Herring, Ian P."

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    Aqueous humor concentration and prostaglandin E2 suppression efficacy of topically applied ophthalmic ketorolac 0.5% and diclofenac 0.1% solutions in dogs with cataract
    Waler, Kayla A. (Virginia Tech, 2020-06-01)
    Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic, anti-pyretic and anti-inflammatory properties in both human and veterinary patients. Topical ophthalmic NSAIDs are commonly employed in the management of intraocular inflammation (uveitis), corneoconjunctival inflammatory disease and pre-operatively to prevent intraoperative miosis during cataract surgery. Despite their routine application in these clinical scenarios, little is known regarding the corneal penetration and relative anti-inflammatory efficacy of the available topical ophthalmic NSAIDs in the dog. Decisions regarding which of these agents to employ are therefore based upon factors such as cost and ease of acquisition as opposed to established efficacy. Objectives: To investigate the relative intraocular penetration and anti-inflammatory efficacy of two commonly utilized topical ophthalmic NSAIDs in dogs, diclofenac 0.1% and ketorolac 0.5%. Animals: Twenty-two client owned dogs (22 operated eyes) presenting to the VTH ophthalmology service for routine cataract surgery for mature or hypermature cataract. Methods: Subjects were randomized to be treated with either topical ketorolac 0.5% or topical diclofenac 0.1% ophthalmic solutions at specified times in the 24-hour period pre-operatively. Aqueous humor samples were obtained intra-operatively and stored for subsequent evaluation of drug concentrations and prostaglandin E2 (PGE2) concentrations via ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and enzyme-linked immunoassay (ELISA) analysis, respectively. Results: Median aqueous humor drug concentrations were significantly higher in dogs treated with ketorolac 0.5% (1311.6 ng/mL) compared to those treated with diclofenac 0.1% (284.9 ng/mL). There was no significant difference in aqueous humor PGE2 concentrations between the two treatment groups. No significant association was determined between aqueous humor drug concentration and PGE2 concentration. There was no significant association between diabetic status and aqueous humor drug concentration or PGE2 concentration in either group. Conclusions and clinical importance: This study suggests that topical ketorolac 0.5% and diclofenac 0.1% are efficacious in decreasing aqueous humor PGE2 concentrations and are equally suitable for use based on their comparable anti-inflammatory profiles. The results of these assays provide clinically relevant information regarding intraocular penetration and anti-inflammatory efficacy of these medications in dogs with cataract.
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    Biochemical and Immunocytochemical Characterization of Canine Corneal Cells Cultured in Two Different Media
    Schorling, Jamie J. (Virginia Tech, 2007-04-26)
    The study purpose was to determine whether canine corneal cultures demonstrate superior growth when cultured in a fully defined epithelial selective medium, Epilife®, compared to Dulbecco's modification of Eagle's medium (DMEM) with fetal bovine serum (FBS), and to characterize cultured canine corneal cells. Superficial keratectomies were performed on three dogs. Samples were trypsinized to separate cell layers. Post-trypsinization, immunohistochemistry confirmed that epithelial cells had been released from the stroma. Both cell populations (presumed epithelial cells and stromal tissues) were cultured in DMEM with FBS or Epilife®. First passage cells were fixed for immunocytochemistry and prepared for PCR. Immunocytochemical staining for pancytokeratin, vimentin, and E-cadherin was evaluated, and immunofluorescence for zonula occludens-1 was attempted. Amplification of cytokeratin 5 (CK5) mRNA was assessed by PCR. Primary presumed epithelial cells grew faster when cultured in DMEM with FBS compared to Epilife®. Stromal tissue segments in Epilife® medium failed to adhere to culture plates, indicating that this medium may inhibit attachment and growth of non-epithelial tissues. Staining of corneal tissue segments confirmed that epithelial layers were pancytokeratin and E-cadherin positive, while stromal cells were vimentin positive. Immunocytochemistry of cultured cells revealed that epithelial cells stained positively for pancytokeratin, vimentin, and E-cadherin, while stromal cells remained only vimentin positive. Greater amplification of CK5 mRNA occurred from epithelial cells grown in Epilife® compared to epithelial cells in DMEM with FBS or the stromal cells. Based on PCR results, Epilife® medium may support retention of the epithelial characteristic of CK5 mRNA expression better than DMEM with FBS.
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    The Biomechanical Response of the Eye, Face, and Orbit to Primary Blast Overpressure
    Alphonse, Vanessa D. (Virginia Tech, 2015-12-08)
    Combat-related blast injuries are occurring more frequently with the increased use of improvised explosive devices in current military conflicts. Though much research has focused on how the body responds to the relatively low loading rates associated with blunt trauma, little is known regarding the response of the body to the higher loading rates associated with blast trauma. While soldiers are surviving once-lethal blast events due to enhanced protective equipment, injuries such as those to the eye and face that were once considered inconsequential, can now be detrimental to long-term healthcare costs and quality of life. Although it is suggested primary blast overpressure (i.e., the shock wave) can cause severe eye injuries, there remains few empirical data in the literature that confirms this. Adding to this, there are currently no testing standards to assess the effectiveness of personal protective equipment during blast exposure. Expanding upon traditional research techniques within the field of injury biomechanics, the research in this dissertation focuses specifically on developing experimental and physical models of the eye, face, and orbit for blast overpressure exposure. Foremost, a porcine eye model is used to quantify eye injury risk from blast overpressure exposure. Subsequently, these biomechanical data are used to develop a physical model of the eye that can be used in lieu of cadaver specimens for blunt and blast loading. Lastly, military spectacles and goggles are examined for effectiveness at protecting the eye during blast exposure. Combined with detailed computer-aided design geometries, these data can be used to validate computational models of the eye, orbit, and face to blast loading. Results from these tests support one theory that shock waves may enter the skull through the orbit, alluding to future work that is essential to more fully understanding the physiological response of the brain and ocular motor system to blast exposure. Ultimately, the experimental methods and analysis techniques disseminated herein serve as a framework for future experimental work related to blast and other high-rate loading scenarios.
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    Comparison of conjunctival pedicle flap to corneal adhesion achieved by Tisseel® fibrin glue, ethyl cyanoacrylate adhesive, ReSure® hydrogel sealant, and conventional suturing with 8-0 VICRYL® suture
    VerHulst, Elodie Marie (Virginia Tech, 2023-02-09)
    Background: Conjunctival pedicle flaps are one of the most frequently employed surgical interventions used to address a variety of sight threatening corneal diseases in veterinary ophthalmic practice. Securing the conjunctiva to the cornea is typically achieved through suturing, which is technically challenging and can result in prolonged surgical times, increased corneal edema, increased scar tissue, foreign body reaction, suture abscess and dehiscence. In human ophthalmology, a number of sutureless techniques to affix ocular tissues are being explored. Specifically, these approaches include synthetic tissue adhesives, bioadhesives, and hydrogel sealants. The proposed advantages of adhesives over suture, include reduced operative times, watertight seals, decreased foreign-body sensation and inflammation, faster healing times and tissue regeneration with original architecture restoration. Objective. To evaluate the maximum tensile force a conjunctival pedicle flap is able to withstand with respect to different fixation methods, i.e., Tisseel® fibrin glue, ethyl cyanoacrylate adhesive, ReSure® hydrogel sealant, or 8-0 VICRYL suture. Animals Studied. Ex-vivo porcine globes Procedures. Following a 500-micron restricted depth lamellar keratectomy, conjunctival pedicle flaps were dissected and secured to corneal defects with either the bioadhesive Tisseel®, or the synthetic adhesives ReSure®, ethyl cyanoacrylate, or 8-0 VICRYL® suture. Harvested corneoconjunctival flap interfaces were clamped to an accelerometer and potentiometer device, and loaded under video surveillance until the point of failure. Peak load at failure was determined for each test and used to compare between sample types. Results. 40 flaps underwent tensile force testing, with 6 being omitted for dehiscence prior to tensile testing. Of the 34 tests included in analysis, 10 conjunctival flaps were secured with suture, 10 with cyanoacrylate, 8 with ReSure® hydrogel sealant, and 6 with Tisseel® fibrin glue. A significant increase in maximum withstood tensile force was recorded between sutured flap fixation when compared with cyanoacrylate glue (p=0.02474), ReSure® hydrogel sealant (p= 0.00000), and Tisseel® fibrin glue (p= 0.00002). Cyanoacrylate fixation was significantly stronger when compared with ReSure® hydrogel sealant and Tisseel fibrin glue (p=0.01194 and 0.01798 respectively). There was no significant difference in adhesion strength between ReSure® hydrogel sealant and Tisseel® fibrin glue (p=0.95675). Conclusions. Conjunctival pedicle flap fixation using 8-0 VICRYL® suture fixation was able to withstand significantly greater maximum tensile force application in comparison with the ReSure®, Tisseel®, or cyanoacrylate adhesives.
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    The Development and Validation of a Biofidelic Synthetic Eye for the Facial and Ocular CountermeasUre Safety (FOCUS) Headform
    Kennedy, Eric A. (Virginia Tech, 2007-08-03)
    There are over 1.9 million eye injuries per year in the United States with over 30,000 patients left blind in at least one eye as a result of trauma. Some of the most severe eye injuries can occur in automobile accidents and from sports related impacts. Eye injuries in the military environment are even more prevalent and are generally more severe than eye injuries to civilians. The rate of eye injuries has dramatically increased in warfare in recent years, rising from 2% of all casualties during World War I and World War II to over 13% of all combat injuries in Operation Desert Storm. While many of the conflict-related eye injuries are caused by shrapnel and other debris, nearly 25% of the injuries are also caused by blunt trauma from motor vehicle and helicopter crashes, falling, and direct hits from blunt objects. In order to develop safety countermeasures effective at preventing these eye injuries, as well as evaluate the eye injury potential of different impacts, it is desirable to have the capability for distinguishing between injurious and non-injurious eye impacts. Current anthropometric test device (ATD) headforms lack instrumentation and facial features to allow detailed assessment of eye or discrete facial injuries. Therefore, the purpose of this dissertation is to present the development and validation of the Facial and Ocular CountermeasUre Safety (FOCUS) headform's synthetic eye and orbit and corresponding eye injury risk criteria.
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    Differential Impact of VEGF and FGF2 Signaling Mechanisms on Flt1 Pre-mRNA Splicing
    Payne, Laura Beth (Virginia Tech, 2016-06-19)
    The human proteome is exponentially derived from a limited number of genes via alternative splicing, where one gene gives rise to multiple proteins. Alternatively spliced gene products, although crucial for normal physiology, are also linked to an increasing number of pathologies. Consequently, a growing focus is currently being placed on elucidating the extrinsic cues and ensuing signaling mechanisms which direct changes in gene splicing to yield functionally distinct proteins. Of note is the dysregulation of the vascular endothelial growth factor (VEGF) receptor, Flt1 and its soluble splice variants, sFlt1_v1 and sFlt1_v2, in the pregnancy-related disorder, preeclampsia. Preeclampsia is characterized by proteinuria and hypertension and is responsible for almost 600,000 maternal and fetal yearly deaths, worldwide. Here, we examined the impact of endothelial mitogens VEGF and FGF2 (fibroblast growth factor 2), both of which are upregulated in preeclampsia, on Flt1 transcript variants in umbilical vein endothelial cells. We tested the hypothesis that VEGF modulates the expression of Flt1 variants via the signaling kinase Akt and its impact on SR proteins. VEGF was observed to induce expression of overall Flt1 mRNA, principally as variants Flt1 and sFlt1_v1. Conversely, FGF2 induced a shift in splicing toward sFlt1_v2 without significant increase in overall Flt1. Based on inhibitor studies, the VEGF and FGF2 signals were transduced via ERK, but with the involvement of different upstream components. We mapped predicted SR protein binding to Flt1 pre-mRNA and identified two candidate proteins, SRSF2 and SRSF3, that may be involved in VEGF- or FGF2-induced Flt1 pre-mRNA splicing. Examination of SRSF2 and SRSF3 relative mRNA expression levels, following inhibition of VEGF- and FGF2-activated kinases, indicates that FGF2 significantly downregulates SRSF3 mRNA levels via PKC-independent activation of ERK. Additionally, our data suggest that FGF2 may impact Flt1 and sFlt1_v1 via SR protein kinases Akt and SRPK, while conversely regulating sFlt1_v2 levels via Clk. We did not find evidence of VEGF-induced Flt1 variant splicing via SR protein kinase activation or SRSF2 and SRSF3 mRNA levels. Thus, VEGF and FGF2 signals were tranduced via related but distinct mechanisms to differentially influence Flt1 pre-mRNA splicing. These findings implicate VEGF and FGF2 and their related intracellular signaling mechanisms in soluble Flt1 regulation.
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    The effects of Nd:YAG laser cyclophotocoagulation on corneal sensitivity, intraocular pressure, aqueous tear production and corneal nerve morphology in the canine eye
    Weigt, Anne Kelley (Virginia Tech, 2001-06-04)
    Corneal ulceration with prolonged healing following Nd:YAG laser cyclophotocoagulation in dogs is a frequent complication. It is hypothesized that these corneal ulcerations may be a form of neurotrophic keratitis due to laser-induced damage to corneal innervation. Fifteen clinically normal dogs had the neodymium:yttrium aluminum garnet(Nd:YAG) laser cyclophotocoagulation performed on the left eye. Each treated eye received 100 Joules of laser energy. Corneal touch threshold (CTT) and Schirmer I tear tests (STT) were performed before the surgery and on days 1,3,5,7,9,11, and 13 post-laser treatment. Applanation tonometry was performed before surgery and twice daily for 14 days post-laser treatment. Eyes were enucleated after 14 days and corneal nerves were stained using a gold chloride technique. Major nerve bundles entering the cornea were quantitated by quadrant, using camera lucida reproductions. Nerve bundle diameters were measured using NIH image computer software on computer-scanned images. Statistical methods included repeated values for analysis of variance for CTT, STT and IOP, and a paired t-test for nerve diameters and bundles. All laser treated eyes had significantly higher CTTs (P<0.05) compared to control eyes for all measurements. Six out of fifteen dogs had evidence of ulcerative keratitis. Intraocular pressure was significantly lower in laser treated eyes compared to control eyes in the a.m. on days 2-9,and 14, and in the p.m. on days 2-11 using a Bonferroni-corrected alpha level (P<0.0039). A significant decrease of one nerve bundle per corneal quadrant was found between the laser treated and control eyes. There was no significant difference in STT or nerve bundle diameters between laser treated and control eyes. Nd:YAG laser cyclophotocoagulation effectively reduces IOP while increasing CTT. The procedure also causes a significant decrease in the number of major nerve bundles entering the cornea, but has no effect on the diameter of those bundles. These findings support the hypothesis that nerve damage and corneal hypoesthesia are etiologic factors in ulcerative keratitis following Nd:YAG laser cyclophotocoagulation.
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    Effects of systemic flunixin meglumine, topical oxytetracycline, and topical prednisolone acetate on tear film proteinases innormal horses
    Rainbow, Marc E. (Virginia Tech, 2004-04-21)
    The purpose of this study was to determine the effects of three medical treatments, topical oxytetracycline, topical prednisolone acetate, and systemic flunixin meglumine, on the activity of two proteinases, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), in equine tear film. The study design consisted of twelve ophthalmically normal horses separated into three groups of four in a cross-over study design. Each group was treated for 5 days with flunixin meglumine (500mg IM bid), topical 1% prednisolone acetate (0.2ml tid), or topical oxytetracycline (0.2ml tid), followed by a 9-day washout period. All topical medications were applied to the left eye and the right eye was treated with a placebo. Tears were collected before the first treatment on day one and the morning following the last treatment on day 5. Tear film proteinase activity was measured using gelatin zymography and measurements of optical density. Statistical analysis of the difference between the treated and untreated eyes and the eyes before and after treatment was performed using mixed effects model for ANOVA. When eyes were compared after treatment, there was no significant difference between treated and placebo eyes for MMP-2 or MMP-9 for any of the treatments. When post-treated eyes were compared to pre-treated eyes, there was a significant decrease in MMP-2 activity in the left eye of horses treated with flunixin meglumine (P=0.0259). There were no differences in MMP-2 and MMP-9 activity for the other treatments. In conclusion, topical 1% prednisolone acetate and topical oxytetracycline did not significantly change MMP-2 or MMP-9 activity in normal equine tear film. Systemic flunixin meglumine had an inhibitory, but questionable, effect on MMP-2 activity in normal equine tear film. This project was funded by Patricia Bonsall Stuart Award for Equine Research.
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    Microstructural and Mechanical Properties of Human Ribs
    Cormier, Joseph Michael (Virginia Tech, 1998-09-16)
    The direction of osteons in cortical bone has been shown to be well correlated with the strongest loading direction of the bone as a whole. Therefore, determining the orientation of osteons in the rib cage is an important step in understanding the behavior of the rib cage under mechanical load. A total of 37 specimens were removed from several rib locations from a male and female cadaver. Eight histological slides were created from each 5 mm long section. Image analysis included the use of a computer algorithm created in Matlab to track the center of each osteon throughout the rib section. Analysis of the results showed variations in the osteon direction between samples taken from the anterior, lateral and posterior surfaces of the rib cage. The average offset angle between the osteon direction and the rib axis was determined to be 4.1, 3.2 and 1.9 degrees for the anterior, lateral and posterior surfaces respectively. The average offset angle for the anterior specimens was significantly higher than that of the posterior rib specimens (P=0.01) The lateral specimens also showed a significantly higher average offset angle than the posterior rib specimens (P=0.01). The results indicate a trend in osteon offset angle between the three locations studied. The offset angle is highest in the anterior region, then decreases in the lateral and is lowest in the posterior regions of the rib cage. Determining the risk of injury from an automobile collision to the thorax requires knowledge of the properties of the skeletal components that comprise the thorax. The purpose of this study was to investigate the strength of human ribs subjected to dynamic three-point bending. A total of four human cadavers were utilized by removing 16 rib sections from the right side of each thorax. One or two sections were removed from a single rib at the lateral, anterior and posterior locations of the thorax. The strain rates resulting from the dynamic loading ranged from 0.5 to 5.44 strains per second. Three-axis strain gage rosettes were used for one series of tests showing small variation of the principal strain axis from the direction of bending. For all subjects, the anterior specimens failed at a significantly lower peak stress than the lateral (p=0.01) and posterior (p=0.01) specimens. The average elastic modulus from all tests was 22 GPa. The average peak stress for all specimens was 115 MPa, with an average peak strain of 11,460 microstrain.
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    A Nonlinear Finite Element Model of the Human Eye to Investigate Ocular Injuries From Night Vision Goggles
    Power, Erik D. (Virginia Tech, 2001-04-20)
    Airbags have been saving lives in automobile crashes for many years and are now being used in helicopters. The purpose of this study was to investigate the potential for ocular injuries to helicopter pilots wearing night vision goggles when the airbag is deployed. A nonlinear finite element model of the human eye was constructed. Ocular structures never before included in finite element models of the eye, such as the fatty tissue, extraocular muscles, and bony orbit were included in this model. In addition, this model includes material properties up to rupture making the eye suitable for large deformation applications. The model was imported into Madymo and used to determine the worst-case position of a helicopter pilot wearing night vision goggles. This was evaluated as the greatest Von Mises stress in the eye when the airbag is deployed. The worst-case position was achieved by minimizing the distance between the eyes and goggles, having the occupant look directly into the airbag, and making initial contact with the airbag halfway through its full deployment. By removing the extraocular muscles, the stress sustained by the eye decreased. Simulations with both the goggles remaining fastened and breaking away from the aviator helmet were performed. Finally, placing a protective lens in front of the eyes was found to reduce the stress to the eye but increase the force experienced by the surrounding orbital bones. The finite element model of the eye proved effective at evaluating the experimental boundary conditions, and could be used in the future to evaluate impact loading on eyes that have been surgically corrected and to model the geometry of the orbital bones.
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    Optic nerve astrocytoma in a dog
    Rozov, Orr; Piñyero, Pablo E.; Zimmerman, Kurt L.; Herring, Ian P.; Matusow, Rachel; Rossmeisl, John H. Jr.; Jortner, Bernard S.; Dreyfus, Jennifer (Wiley, 2016)
    Intraocular neoplasms in dogs are uncommon in comparison with other anatomic locations [1–4]. Over 75% of these cases are attributed to melanocytic neoplasia [1]. A majority of the remaining cases (~22%) are comprised of lymphoma, metastatic neoplasia, iridociliary epithelial tumors, optic nerve meningiomas, and histiocytic sarcomas in decreasing order of frequency [1, 2]. Rarely, optic nerve astrocytomas have been reported in humans, dogs, and horses [5–7]. In humans, astrocytomas involving the optic nerve are uncommon accounting for only about 1% of neoplasms at this site in comparison with 25% of neoplasms occurring in the brain [5, 8–14]. Most of these neoplasms occur unilaterally, are benign, and arise in children under 10 years of age; those involving the cerebellum have a more favorable prognosis [8, 14]. These younger patients commonly have an underlying familiar disorder such as neurofibromatosis. In older patients in their fourth and fifth decade of life, astrocytomas more commonly involve the cerebrum with a less favorable prognosis and can be associated with familiar disorders such as Li–Fraumeni syndrome [13, 15–17]. Most canine ocular astrocytoma cases are sporadic and not associated with any familial disorder [1, 13, 18–21]. However, Thomas et al. demonstrated a genomic risk factor associated with frequency of chromosome copy number aberrations within canine brain astrocytomas and tumor grade [22]. Similar to humans, canine astrocytomas account for less than 1% of ocular and optic nerve neoplasms and 10–36% of primary intracranial neoplasms [1, 4, 16–18, 20, 21, 23]. There appears to be a breed predisposition for development of intracranial astrocytomas in English Toy Spaniels, Boston Terriers, French Bulldogs, Boxers, and English Bulldog with a peak prevalence at 7– 8 years and 1.5 odds ratio in favor of larger versus smaller breeds [13, 23]. These risk factors have not been shown in association with canine ocular forms of this neoplasm [1, 16, 17]. Gender as a risk factor has not been described for either anatomic location [1, 13, 16–18, 23]. Case reports related to ocular astrocytomas are still rare in veterinary literature. The purpose of this report is to add to this sparse body of information. This report presents the clinical, histological, and immunohistochemical features of an optic nerve astrocytoma in a dog.
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    Perioperative Administration of Topical Dorzolamide Hydrochloride/Timolol Maleate Reduces Postoperative Ocular Hypertension in Dogs Undergoing Cataract Surgery
    Matusow, Rachel Brodman (Virginia Tech, 2015-05-15)
    Development of cataracts is a relatively frequent ocular disease of the dog and cataract extraction via phacoemulsification (PE) is commonly performed by veterinary ophthalmologists. Postoperative ocular hypertension (POH) describes the elevation of pressures within the eye during the acute postoperative period and can result in vision loss and poor surgical outcome. Relatively little is known about risk factors or efficacy of prophylactic treatment for POH, and current clinical practice with regard to pressure monitoring and medication administration are highly variable. The literature on POH prophylaxis in humans indicates that improved efficacy may be achieved with a multi-dose approach and that dorzolamide hydrochloride/timolol maleate (DHTM) may be more efficacious than other pressure lowering medications. The canine literature on POH prophylaxis is limited and DHTM has not yet been evaluated despite common use in the clinical setting. Our objectives, therefore, were to investigate risk factors for POH and to test the hypothesis that perioperative topical ophthalmic dorzolamide hydrochloride 2%/timolol maleate 0.5% (DHTM) reduces the prevalence and/or severity of postoperative ocular hypertension (POH) in dogs undergoing cataract extraction by phacoemulsification (PE). We employed a randomized double-masked placebo-controlled study and enrolled 103 dogs (180 eyes) presenting for unilateral or bilateral PE. Select historical, signalment, ophthalmic examination, and surgical data was collected. Dogs were treated with DHTM or Blink Contacts (BC) placebo at 14- and 2-h preoperatively and at conclusion of surgical closure. Intraocular pressures were assessed by rebound tonometry at 2, 4, 6, and 8 hours after surgery and at 8 am the following morning. POH was defined as IOP>25 mmHg and intervention consisted of latanoprost 0.005% if IOP rose to 26 mmHg - 45 mmHg or surgeon treatment of choice if >45 mmHg. Our investigation of risk factors yielded a statistically significant association only with surgeon and surgical time, which were also associated with one another. DHTM significantly reduced the prevalence of POH in comparison with BC (26% versus 49% of eyes, OR=0.36; 34% versus 62% of dogs, OR=0.32). There was also a trend toward reduction of POH severity in DHTM-treated eyes (POH value 37.17±10.47 mmHg with BC, 32.67±6.39 mmHg with DHTM). DHTM-treated eyes that developed POH were significantly more likely to respond favorably (1 hour post-treatment IOP <25 mmHg) to treatment with latanoprost than those in the BC group (76% versus 51%, OR=3.87). We conclude that multi-dose perioperative administration of DHTM may be recommended in dogs undergoing PE to reduce the risk of POH and improve responsiveness of POH to treatment with latanoprost.
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    Retrobulbar neurolytic ethanol injection for the treatment of end-stage canine glaucoma
    Enders, Andrew Michael (Virginia Tech, 2019-06-11)
    Background: Glaucoma is a chronic ocular disease of both dogs and humans that results in blindness and ocular discomfort. Most commonly, end-stage glaucomatous eyes in dogs are enucleated to provide comfort. This intervention requires significant financial investment, general anesthesia, and has a psychological impact on some owners. Retrobulbar neurolytic injections are used in humans to provide immediate and long-acting pain relief, while simultaneously preserving the globe. Objectives: To determine the safety and efficacy of retrobulbar neurolytic ethanol injection in canine eyes with end-stage glaucoma. Animals: 16 client-owned dogs (19 eyes) diagnosed with end-stage glaucoma. Methods: All eyes underwent an ophthalmic examination, including Schirmer Tear Testing (STT), intraocular pressure (IOP) measurement, corneal touch threshold (CTT), anterior and posterior segment examination, and fluorescein staining. Subjects were sedated and administered a retrobulbar block with bupivacaine, followed by retrobulbar injection of ethanol or saline solution. At specified time points after the procedure, clients assessed their pet's comfort and side effects of the injections via survey. Subjects returned for enucleation. Owner perceived comfort after the enucleation was assessed at identical post-procedure time points and compared to that achieved with retrobulbar ethanol injection or control solution. Overall client satisfaction with each procedure, as well as the effects of retrobulbar ethanol injection on STT, IOP, CTT, and histological changes in retrobulbar tissues were investigated. Results: Retrobulbar neurolytic ethanol injections did not signficiantly improve owner perceived comfort compared to control group treatment or provide more comfort than enucleation. Retrobulbar ethanol injections did not signficantly lower IOP, but did significantly elevate CTT. There was a trend towards lower STT in eyes receiving retrobulbar ethanol injections. Retrobulbar ethanol injections were safe, well tolerated, and no differences in client satisfaction with particpation in the study were noted in either injection group. Histologically, globes in the treatment group displayed significantly greater inflammation and fibrosis; retrobublar tissue samples were not significantly different between control and treatment groups with regard to inflammation or fibrosis. Conclusions and Clinical Importance: Retrobulbar neurolytic ethanol injections were not determined to be an effective globe-sparing alternative treatment to provide analgesia for end-stage canine glaucoma. Enucleation remains an effective way to provide comfort to dogs with elevated IOP.
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    The Role of Local Material Properties in Modeling Fracture Tolerance of the Human Thorax
    Stitzel, Joel D. (Virginia Tech, 2003-09-19)
    This dissertation presents the results of dynamic material tests and computational modeling exploring the effects of regional rib mechanical properties on thoracic fracture patterns. Test coupon modeling was used to verify the test setup. These material properties were incorporated into a human body computational model. The data from the material tests for all subjects indicate a statistically significant increase in the average stiffness and average ultimate stress for the cortical bone specimens located in the lateral (11.9 GPa modulus, 153.5 MPa ultimate stress) portion of the ribs versus the anterior (7.51 GPa, 116.7 MPa) and posterior (10.7 GPa, 127.7 MPa) rib locations. The results from computational modeling for both frontal and lateral impacts illustrate that the location and number of rib fractures are altered by the inclusion of rib material properties that vary by region. A sensitivity analysis of the effects of altering the failure strain criteria on the number of rib fractures predicted is performed revealing improved sensitivity of the modified THUMS model versus the original THUMS model for failure strains from 0.8 to 1.8%. The results from the small specimen tests are compared to results obtained for three-point bending of whole human rib sections.
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    Spring Mediated Cranioplasty for the Treatment of Craniosynostosis
    Hurst, William James (Virginia Tech, 2003-04-22)
    Craniosynostosis is a disorder characterized by the premature fusion of one or more cranial sutures in the infant skull, resulting in an abnormal shape of the cranium. An effective surgical procedure for treatment of this disorder has been developed and is currently use called "Dynamic Spring Mediated Craniofacial Reshaping." This technique involves surgical removal of the fused suture and insertion of springs to expand the gap created by the suture removal in order to gradually reshape the skull to a more desirable shape. There were three primary objectives of this research: develop a device that could fabricate type 316 stainless steel wireform springs having consistent mechanical characteristics, evaluate the performance of the device, and develop a mathematical model to predict the mechanical characteristics of the fabricated springs. Use of the mathematical model facilitates further research to be performed that could determine the most effective use of the "Dynamic Spring Mediated Craniofacial Reshaping" surgical procedure.
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    Static and Dynamic Stress/Strain Properties for Human and Porcine Eyes
    Voorhies, Katherine Desiree (Virginia Tech, 2003-04-22)
    Every year, more than 2.4 million eye injuries occur in the United States, with over 30,000 of those injured left blind in at least one eye as a result. Computer modeling is one of the most versatile ways to study ocular trauma, however, existing models lack accurate stress and strain properties for ocular globe rupture. A pressure system was built to examine static and dynamic globe rupture pressures for healthy postmortem human and porcine (pig) eyes. Maximum rupture stress for the quasi-static tests was found to be 11.17MPa for human tissue and 12.08MPa for porcine tissue, whereas stress for the dynamic tests was found to be 30.18MPa for human tissue and 26.01MPa for porcine tissue. Maximum rupture stress results correlate well with static material properties used in published research (9.4MPa), and dynamic properties of 23MPa found in published research. Healthy postmortem human eyes were ruptured statically and dynamically to determine the relationship between stress and strain for the ocular globe under intraocular pressure loading. Stress-strain relationships were investigated and values for the elastic modulus were found to be slightly lower than that previously published. This research shows that it is important to differentiate between tissue type, and static versus dynamic failure properties before drawing conclusions from computer models and other published research. Now that rupture can be accurately determined, safety systems designed to protect eyesight in automotive, sports, and military applications can also be applied to protect the quality of life for humans in these applications.
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    Statistical Analysis and Computational Modeling of Injuries in utomobile Crashes
    Jernigan, Mary Virginia (Virginia Tech, 2002-04-16)
    Although airbags have reduced the incidence of fatal and severe injuries in automobile collisions, they have been shown to increase the risk of less severe injuries. The purpose of this research was to investigate particular occupants and injury types in automobile crashes in order to identify national trends in injury incidence, type, and severity. A statistical analysis was performed in order to determine the effects of airbag deployment on incidence and severity of various injury and occupant types. In addition, a computational modeling study aimed to recreate actual automobile crashes that occurred in order to identify injury mechanisms and occupant kinematics during the crash. The specific studies performed were designed to investigate the effects of frontal airbags on: skin injuries, burn injuries, eye injuries, orbital fractures, severe upper extremity injuries, and pregnant occupant injuries. The statistical analyses revealed several significant findings in injury trends related to occupant exposure to airbag deployment. In particular, occupants in frontal crashes were significantly at a higher risk to sustain a skin injury (p=0.00), a burn injury (p=0.02), a corneal abrasion (p=0.03), and a severe upper extremity injury (p=0.01) when exposed to an airbag deployment, than when not exposed to an airbag deployment. In addition, female occupants were at a statistically higher risk of sustaining an airbag induced skin injury than males (p=0.00). Finally, within a 95% confidence interval, older occupants were at a higher risk for sustaining both airbag induced burn injuries, and severe upper extremity injuries. While occupants in crashes with lower impact velocities were at a higher risk for airbag induced burn injuries, occupants in crashes with higher impact velocities were more likely to sustain a severe upper extremity injury. The airbag increased the incidence of eye injuries for occupants in frontal crashes, however, it also decreased the severity of the associated eye injuries. In particular, occupants who sustained an orbital fracture when exposed to airbag deployment sustained mostly closed, less severe orbital fractures, while occupants not exposed to airbag deployment much more often sustained more severe, open, displaced, or comminuted orbital fractures. While the airbag was shown to increase the risk of some injuries to particular occupants involved in specific crash types, the airbag appears to have provided a beneficial protective effect as it also reduced the severity of all injuries observed.
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    Tear Film VEGF in Dogs with Vascularizing Corneal Disease
    Brantman, Karen Renee (Virginia Tech, 2013-06-06)
    This body of work encompasses two studies: the collection of canine tears via a novel polyester
    rod and the comparison of VEGF-A concentrations in tears from dogs with normal and
    vascularized corneas. The first study used polyester rods for tear collection in dogs. Fluid volume and VEGF recovery characteristics, as well as potential binding of VEGF to the rod, were determined. Tears were harvested from normal dogs using rods and glass capillary tubes. Tears were assayed for tear film VEGF using a commercial canine VEGF sandwich ELISA kit. Dilutions of VEGF standard were wicked into the rods or drawn into capillary tubes, eluted, and assayed. Percent volume recovery is adequate for polyester rods as is percent VEGF recovery. VEGF is detectable in normal canine tears.The second study harvested tear samples from eyes of dogs with vascularizing corneal disease, as well as the contralateral unaffected eye of unilaterally diseased dogs, and normal dogs. Vascularization scores were assigned to diseased eyes and tear film VEGF concentration was assayed as above. Mean tear film VEGF concentration of diseased eyes did not differ from control eyes, and was not correlated with disease process, extent of vascularization, or other parameters. Tear film VEGF in unaffected eyes was significantly higher than control and vascularized eyes. Canine tear film VEGF exceeds biologically active concentrations, but does not correlate with state of corneal vascularization. VEGF-related control of corneal vascularization may be mediated by other proangiogenic factors.
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    Tear lacritin concentrations in canine keratoconjunctivitis sicca
    Disney, Julia L. (Virginia Tech, 2017-06-26)
    Background: Keratoconjunctivitis sicca (KCS) is a chronic ocular disease of both dogs and humans that can result in ocular discomfort, corneal opacification, and vision loss. Lacritin, a protein found in the tears of many species, has been shown to play a role in lacrimation and corneal health. Because of its role as a potential lacrimostimulant, assessment of endogenous lacritin levels could reveal a correlation between lacritin and tear production in the dog. Objectives: To determine if tear lacritin concentrations are decreased in canine eyes affected by KCS. Animals: 58 client-owned dogs (tear samples from 55 eyes with normal tear production and 55 eyes diagnosed with KCS). Methods: All eyes underwent an ophthalmic exam, including Schirmer Tear Testing (STT), anterior segment assessment, and tear sample collection. Tear samples were evaluated for their total protein concentrations via BCA assay and lacritin concentrations via ELISA. Results: Total protein of canine tears is increased in KCS-affected eyes as compared to normal eyes. Tear lacritin as a component of total tear protein is significantly decreased in tears from KCS-affected eyes. When measured as a concentration (mass per volume of aqueous tears), lacritin is not significantly different between KCS-affected eyes and normal eyes, nor were they strongly correlated to STT values. Conclusions and Clinical Importance: Total tear protein levels were significantly increased in canine KCS. When quantified as a proportion of total tear sample protein, tear lacritin levels are decreased in KCS-affected eyes. Relative to tear volume, tear lacritin levels are not significantly different between KCS-affected eyes and normal eyes. Assessment of lacritin supplementation in canine KCS is warranted to evaluate potential effects on lacrimation and ocular surface health.
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    Vascular Endothelial Growth Factor in the Aqueous Humor of Dogs With and Without Intraocular Disease
    Sandberg, Christina Ann (Virginia Tech, 2009-06-08)
    Vascular endothelial growth factor A (VEGF) is a potent mediator of blood vessel formation throughout the body. Intraocular diseases characterized by inflammation, hypoxia or neoplasia induce new blood vessel formation within the eye. The end result of such blood vessel formation may be blinding sequellae such as glaucoma from outflow obstruction or hyphema from intraocular hemorrhage. Elevated VEGF concentrations in the aqueous humor and vitreous are documented in a number of human intraocular disease processes, including tumors, retinal detachment and uveitic glaucoma. Pharmacotherapy inhibiting VEGF expression demonstrates promise for control of some of these ophthalmic conditions. We quantified and compared VEGF concentrations in canine aqueous humor samples from 13 dogs with normal eyes and 226 eyes from 178 dogs with a variety of ophthalmic diseases by ELISA. Dogs with primary cataract, diabetic cataract, primary glaucoma, uveitic glaucoma, aphakic/pseudophakic glaucoma, retinal detachment, lens luxation and neoplasia were evaluated. Elevated VEGF concentrations were found in all disease conditions tested as compared to normal dogs excepting cataracts and diabetic cataracts. Elevated aqueous humor VEGF concentrations were found in dogs with pre-iridal fibrovascular membranes (PIFM) as compared to dogs without PIFM. These results are consistent with the hypothesis that VEGF has a role in the causation or progression of a variety of canine ocular disorders.