Biomedical subjects

Brian C Gilger

Publications and source records attributed to Brian C Gilger.

At least 19 recordsLinked to original sources

PubMed2006

A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis.

PURPOSE: To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. METHODS: A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years. RESULTS: Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant. CONCLUSIONS: Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.

Absorbable Implants↗

PubMed2006

Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses.

OBJECTIVE: To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. ANIMALS: 11 healthy adult horses. PROCEDURE: Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured. RESULTS: Mean +/- SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 +/- 0.37 microg/mL, 2.35 +/- 0.78 microg/mL, and 2.40 +/- 0.29 microg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean +/- SD voriconazole concentration in AH after a single orally administered dose was 0.86 +/- 0.22 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.

Administration, Oral↗

PubMed2005

Preclinical evaluation of a novel episcleral cyclosporine implant for ocular graft-versus-host disease.

PURPOSE: To develop a local drug delivery system that provides therapeutic cyclosporine levels to treat lacrimal gland graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. METHODS: Episcleral cyclosporine implants were manufactured with a silicone-based matrix design, and in vitro release rates were determined. Preclinical evaluation included toxicology (clinical examination, serial electroretinography, and histopathology) in normal rabbits and dogs, pharmacokinetics in normal rabbits, and pharmacodynamics in a canine model of aqueous tear deficiency and keratoconjunctivitis sicca. RESULTS: The cyclosporine implants showed sustained release of drug over time with in vitro assays. Histopathology showed normal ocular tissues in both dogs and rabbits 6 months after implantation. The cyclosporine implant produced lacrimal gland drug levels 1 to 2 log units higher than those reported with a variety of topical cyclosporine formulations and oral administration. The cyclosporine implant was effective in a canine model of keratoconjunctivitis sicca, with all animals able to discontinue topical cyclosporine and maintain normal Schirmer scores over a 6-month follow-up. CONCLUSIONS: This preclinical evaluation showed that the episcleral cyclosporine implant was safe, delivered potentially therapeutic cyclosporine levels to the lacrimal gland, and showed efficacy in a clinically relevant model of keratoconjunctivitis sicca. The episcleral cyclosporine implant shows promise in reducing the morbidity associated with lacrimal gland graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. In addition, continuous release of cyclosporine in the subconjunctival space with the episcleral implant was an effective means of delivering drug to the ocular surface and may have potential in treating other ocular inflammatory diseases.

Animals↗

PubMed2004

Cosmetic globe surgery in the horse.

Effects of traumatic injury or inflammation on the equine eye can be catastrophic. These ocular conditions can frequently result in blindness or chronic pain. In addition to blindness and pain, permanent unsightly cosmetic defects can occur. This article addresses options available for improved cosmetic outcome in horses with ocular scars or requiring enucleation. Many of these options have been described in detail previously. New information has been added to the discussion of each option where pertinent.

Animals↗

PubMed2004

Equine glaucoma.

Glaucoma is a diverse group of vision-impairing disorders that have as a common bond an elevation of intraocular pressure(IOP) to a level incompatible with the health of the eye. Glaucoma can be congenital, primary, or secondary. Congenital equine glaucoma is associated with developmental abnormalities of the iridocorneal angle or, in many cases, with the more severe anterior segment dysgenesis.

Animals↗

PubMed2004

Equine recurrent uveitis: new methods of management.

Equine recurrent uveitis (ERU) is one of the most common causes of blindness in horses. Until recently, treatment of this condition consisted only of symptomatic therapy, typically with steroidal and nonsteroidal medications. A better understanding of the disease process(es) has permitted new medical and surgical therapies that have recently been described. This article highlights clinical features of ERU, the causes of ERU, and new management and treatment options for horses with ERU.

Animals↗

PubMed2004

Novel approaches to ocular drug delivery.

Recent advances in surgical techniques, therapeutic approaches and materials sciences have produced revolutionary new therapies for ocular diseases. The development of prodrug formulations and permeability enhancers, sustained-release drug delivery devices, novel injectable medications and new and improved vectors, both viral and non-viral, for delivery of genes to all segments of the eye has greatly increased the chances of success in treating eye diseases. This review will discuss the most recent advances in drug delivery systems for the treatment of ocular diseases.

Animals↗

PubMed2003

Use of thermokeratoplasty for treatment of ulcerative keratitis and bullous keratopathy secondary to corneal endothelial disease in dogs: 13 cases (1994-2001).

OBJECTIVE: To evaluate the outcome of thermokeratoplasty for treatment of ulcerative keratitis and bullous keratopathy secondary to corneal endothelial disease in dogs. DESIGN: Retrospective study. ANIMALS: 13 dogs. PROCEDURES: Medical records from 1994 to 2001 for dogs evaluated because of ulcerative keratitis and bullous keratopathy and treated with thermokeratoplasty were reviewed. RESULTS: There were 7 spayed females, 5 castrated males, and 1 sexually intact male, ranging from 6 to 16 years of age. Ten dogs had endothelial degeneration, and 3 dogs had breed-related endothelial dystrophy. All dogs had bullous keratopathy, characterized by microbullae formation that was detected via biomicroscopy. Recurrent or nonhealing corneal ulcers were detected unilaterally in 5 dogs and bilaterally in 8 dogs. Mean +/- SD duration from thermokeratoplasty until ulcerations were healed for all dogs was 2.2 +/- 1.1 weeks. All dogs that underwent thermokeratoplasty for nonhealing corneal ulceration secondary to endothelial disease and corneal edema had epithelial wound healing and resolution of corneal ulceration. Mean duration of treatment (ie, topical treatment required until resolution of ulceration) was significantly less after thermokeratoplasty than duration of treatment (with multiple treatments) prior to referral. CONCLUSIONS AND CLINICAL RELEVANCE: It may be necessary to perform thermokeratoplasty of the entire cornea to prevent recurrence of ulcerations in areas that have not been treated with thermokeratoplasty.

Animals↗

PubMed2003

Use of a hydroxyapatite orbital implant in a cosmetic corneoscleral prosthesis after enucleation in a horse.

A hydroxyapatite orbital implant was used after enucleation of an eye from a 5-year-old performance horse. A custom-made corneoscleral prosthesis was made and fitted over the hydroxyapatite implant. The implant and surgery were well tolerated. Placement of a cosmetic prosthesis is desired after enucleation of equine eyes to allow horses to return to competition. Synthetic spheres consisting of methylmethacrylate or silicone have been used, although reported complications have included extrusion, infection, and poor cosmetic results. Hydroxyapatite orbital implants made from marine coral allow vascular and fibrous tissue growth from the host orbit into the implant, which decreases the possibility of implant extrusion or infection and allows enhanced healing of defects in the overlying conjunctiva. Extraocular muscle fixation onto the implant permits motility and assists in the prevention of implant extrusion.

Animals↗

PubMed2003

Intraocular extramedullary plasmacytoma in a cat.

An 8-year-old, castrated male Domestic Short-haired cat was referred for evaluation of a possible intraocular neoplasm following previous ocular trauma. The eye was blind, and uveitis and an iridal mass were noted on examination. An enucleation was performed and the mandibular lymph node excised. Histopathologic examination revealed neoplastic proliferation of plasma cells in the iris and lymph node. No other evidence of disseminated disease was detected. This is the first case reported of an intraocular extramedullary plasmacytoma in the cat. The variation in clinical manifestations and potential association with multiple myeloma are not known at this time. Disseminated metastasis from a primary plasmacytoma of the uveal tract could also involve the bone marrow and be indistinguishable from multiple myeloma. Early enucleation, as in trauma-associated sarcomas, may be indicated to prevent metastasis. Periodic systemic evaluation for evidence of multiple myeloma should be performed.

Animals↗

PubMed2002

Nasal adenocarcinoma with diffuse metastases involving the orbit, cerebrum, and multiple cranial nerves in a horse.

A 9-year-old Trakehner gelding was examined because of right exophthalmus. Clinical findings included a lack of menace response in the right eye, reduced direct and consensual right pupillary light reflexes, ventrolateral strabismus of the right eye, mild right-sided facial asymmetry, a head tilt to the left, and increased extensor tone in the right limbs. Findings were suggestive of a multifocal lesion affecting the right forebrain; right optic, oculomotor, and facial nerves; and left vestibulocochlear nerve. Ultrasonographic examination of the right eye revealed a vascular retrobulbar mass. Computed tomographic imaging revealed a mass that filled the nasal cavity and invaded the forebrain. Necropsy revealed an undifferentiated nasal adenocarcinoma affecting the orbit with metastases to the right parotid gland, cranial cervical lymph nodes, fascial planes of the neck, and lungs. No evidence of direct involvement of the right facial and left vestibulocochlear nerves was found, suggesting the possibility of paraneoplastic peripheral neuropathy.

Adenocarcinoma↗

PubMed2002

Causes of uveitis in dogs: 102 cases (1989-2000).

Uveitis is one of the most common ocular diseases and one of the most common causes of blindness in dogs. The purpose of this retrospective study was to correlate the signalment, history, clinical signs and ophthalmic findings of dogs with uveitis with the underlying etiology. We conducted a retrospective study of 102 dogs presented to the NCSU-VTH from 1989 to 2000 with clinical signs of uveitis. Medical records of dogs presented for uveitis were reviewed. Dogs were included in the study only if a complete diagnostic work-up database was collected, if sufficient follow-up was documented, and if the uveitis was not secondary to trauma or a hypermature cataract. The mean age +/- SD of all dogs in this study was 6.2 +/- 3.6 years. There were 33 intact and 16 castrated males, and 14 intact and 27 neutered females. Fourteen breeds were represented, with the Golden Retriever (n = 14) most common. Fifty-nine dogs (58%) were diagnosed with idiopathic/immune-mediated uveitis, neoplasia was diagnosed in 25 dogs (24.5%) and 18 dogs (17.6%) were diagnosed with infectious causes of uveitis. Aqueous flare was the most common clinical sign, occurring in 88 dogs (86%). The most common infectious organisms associated with uveitis in the dogs of this study were Ehrlichia canis (n = 7). Lymphosarcoma (n = 17) was the most common neoplasm. In approximately 60% of dogs presenting for uveitis an underlying cause was not found, and a diagnosis of immune-mediated or idiopathic uveitis was made. However, approximately 25% of dogs had ocular and/or systemic neoplasia (with 17% of cases having lymphosarcoma) and 18% with an underlying infectious cause for uveitis. Because of the high percentage of systemic disease associated with uveitis in dogs, extensive diagnostic testing is recommended before instituting symptomatic anti-inflammatory therapy.

Animals↗

PubMed2002

Bilateral proliferative keratitis in a Domestic Long-haired cat.

A 9-year-old, female spayed, Domestic Long-haired cat was presented with bilateral, progressive, pink-white corneal opacities. The referring veterinarian had diagnosed feline herpesvirus-1 (FHV-1) keratitis though diagnostics for FHV-1 had not been performed and treatment with antibiotics and antivirals did not improve the condition. Histopathology showed neutrophils, plasma cells and lymphocytes, but no eosinophils or mast cells. Routine diagnostics did not find an underlying cause, but Southern blot analysis for FHV-1 was positive. The cat responded to topical corticosteroids and cyclosporine when used consistently.

Animals↗

PubMed2002

Expression of a chemokine by ciliary body epithelium in horses with naturally occurring recurrent uveitis and in cultured ciliary body epithelial cells.

OBJECTIVE: To determine whether a chemokine (RANTES)-like protein expressed by ciliary epithelium plays a role in uveitis. SAMPLE POPULATION: 3 clinically normal horses intradermal, 5 eyes from 5 horses with recurrent uveitis, and 10 normal eyes from 5 age- and sex-matched horses. PROCEDURE: Cross-reactivity and sensitivity of recombinant human (rh)-regulated upon activation, normal T-cell expressed and secreted (RANTES) protein were evaluated in horses by use of intradermal hypersensitivity reactions and a chemotaxis assay. Aqueous humor and ciliary body of eyes from clinically normal horses and horses with uveitis were examined for RANTES expression by use of an ELISA and reverse transcription-polymerase chain reaction (RT-PCR). Expression of RANTES mRNA and protein content of primary cultures of equine ciliary pigmented epithelial cells (RT-PCR) and culture supernatant (ELISA) were measured 6 or 24 hours, respectively, after cultures were stimulated with interleukin-1beta and tumor necrosis factor-alpha. RESULTS: Strong reactions to intradermal hypersensitivity testing and significant chemotaxis of equine leukocytes to rh-RANTES wereas observed. Aqueous humor of eyes from horses with uveitis contained increased concentrations of rh-RANTES-like protein (mean +/- SD, 45.9+/-31.7 pg/ml), compared with aqueous humor from clinically normal horses (0 pg/ml). Ciliary body from horses with uveitis expressed RANTES mRNA, whereas ciliary body from clinically normal horses had low mRNA expression. Stimulated ciliary pigmented epithelial cells expressed increased amounts of rh-RANTES-like protein (506.1+/-298.3 pg/ml) and mRNA, compared with unstimulated samples. CONCLUSIONS AND CLINICAL RELEVANCE: Ciliary epithelium may play a role in recruitment and activation of leukocytes through expression of RANTES.

Animals↗

PubMedDate not supplied

Bilateral nodular lymphocytic conjunctivitis in a horse.

A Russian jumper horse presented because of an ocular perilimbal conjunctival mass and, on clinical examination, two bilateral conjunctival masses were found, of different size and conformation. Attempts at complete excision of the left eye mass and excisional biopsy of the right eye mass were performed. The left eye mass recurred rapidly, but resolved completely after topical corticosteroid therapy. The two lesions had similar histopathologic features, characterized by focal, chronic, primarily lymphocytic conjunctivitis with follicular lymphoid hyperplasia. Special histopathologic staining techniques (Gomori methenamine silver and acid fast stains) and immunohistochemistry (for CD3, BLA36 and lysozyme) failed to reveal any etiologic agents and indicated an inflammatory lesion composed of a heterogeneous population of lymphocytes and macrophages (nodular lymphocytic conjunctivitis). The lesions were indistinguishable, clinically and behaviorally, from what has been reported as 'conjunctival pseudotumor' in the horse. Equine conjunctival pseudotumor/nodular lymphocytic conjunctivitis has been reported to be unilateral and have a good prognosis after partial or complete surgical excision. This is the first reported case of bilateral nodular lymphocytic conjunctivitis in a horse and for which surgical excision alone was not curative.

Animals↗

PubMedDate not supplied

Immune-mediated keratitis in horses: 19 cases (1998-2004).

OBJECTIVE: The purpose of this study is to describe clinical and histologic findings, treatment, and outcome of horses with suspected immune-mediated keratitis (IMMK). DESIGN: Retrospective study. ANIMALS: Nineteen horses that presented to NCSU-VTH from 1998 to 2004 with IMMK. Procedures Information retrieved from the medical records included signalment, duration of clinical signs, therapy prior to initial examination, ophthalmic abnormalities, diagnostics performed, therapy instituted, and long-term vision. RESULTS: Nineteen horses (22 eyes) were diagnosed with IMMK. Three distinct clinical groups were identified based on the depth of the lesion in the cornea: superficial stromal (n = 11 eyes), midstromal (n = 6 eyes), or endothelial (n = 5 eyes). Horses ranged from 5 to 19 years of age, with a mean age +/- SD of 11.9 +/- 3.6 years. Eleven horses had 12 months or greater duration of clinical signs of corneal disease prior to referral. Overall there was a mean duration of 11.8 +/- SD 8.3 months. Superficial stromal keratitis appeared as a superficial stromal cellular infiltrate with diffuse vascularization. Midstromal keratitis appeared as midstromal cellular infiltrate with mild, surrounding corneal edema and vascularization. Endothelial disease appeared as endothelial cellular infiltrate with diffuse corneal edema. In all types of IMMK, signs of uveitis or severe discomfort were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Horses with superficial IMMK responded to topical medical therapy, but responded best to surgical removal of the lesion. Horses with midstromal keratitis responded to topical cyclosporine therapy. Endothelial disease was the least amenable to therapy.

Animals↗

PubMedDate not supplied

Ocular parameters related to drug delivery in the canine and equine eye: aqueous and vitreous humor volume and scleral surface area and thickness.

OBJECTIVE: To measure the ocular surface area, scleral thickness, and the aqueous and vitreous humor volumes in the canine and equine eye. Animals studied Fourteen canine and 16 equine cadaver eyes. PROCEDURE: Eyes were measured either fresh or following fixation in formalin. Ocular surface area was calculated using the fluid displacement method. Globes were hemisected and aqueous and vitreous humor were collected and quantitated. Scleral thickness was measured by digital caliper, by image projection, and by ultrasonic biomicroscopy (UBM). RESULTS: Mean +/- standard deviation (SD) scleral surface areas in canine and equine eyes were 12.87 +/- 2.24 and 57.23 +/- 5.63 cm2, respectively. Mean +/- SD aqueous humor volume was 0.77 +/- 0.24 in the dog and 3.04 +/- 1.27 mL in the horse. Mean vitreous humor volume was 1.7 +/- 0.86 mL for the canine eye and 26.15 +/- 4.87 mL for the equine eye. In canine and equine eyes, the sclera was thinnest at the ocular equator: 0.34 +/- 0.13 mm (canine) and 0.53 +/- 0.1 (equine). There were no significant differences between the direct caliper and projected thickness measurements or differences between measurements in the superior, inferior, nasal, and temporal quadrants of the eye. Scleral thickness in fresh tissue was greater than in fixed tissue at most sites. CONCLUSIONS: The UBM measurement method appeared to be most consistent and reproducible when compared to direct measurement techniques. Formalin fixation of the eyes was associated with significantly thinner scleral tissue than with fresh ocular tissue.

Animals↗

PubMedDate not supplied

Effect of ophthalmic Nd:YAG laser energy on intraocular lenses after posterior capsulotomy in normal dog eyes.

OBJECTIVE: To determine Nd:YAG laser energy requirements for posterior capsulotomy and intraocular lens (IOL) damage threshold for foldable acrylic IOLs as compared to traditional polymethylmethacrylate (PMMA). MATERIALS AND PROCEDURES: Four groups of five-six fresh canine cadaver eyes were used in this study. The groups included (1) unaltered eyes (2) aphakic eyes (3) eyes implanted with PMMA IOLs, and (4) eyes implanted with acrylic IOLs. Laser energy was delivered to the posterior capsule in grid fashion for 10 sites each of five levels of laser energy ranging from 0.5 mJ to 9 mJ. Number of successful capsulotomy sites was recorded based on slit-lamp observation. Sites of IOL damage were evaluated using scanning electron microscopy (SEM). Statistical analysis of number of capsulotomies and IOL defects per laser energy level was conducted among and between groups using anova with Tukey's HSD test. RESULTS: When comparing groups (a) including all energy levels (n = 25) and (b) by specific energy levels (n = 5), there was no significant difference (P < 0.05) in number of successful capsulotomy sites between IOL types. The 50% incidence threshold for successful capsulotomy was 2.74 mJ for acrylic IOLs and 2.64 mJ for PMMA IOLs. Energy-dependent damage to both types of IOL was detected for medium, high-medium, and high laser energy. Calculated 50% damage threshold was 4.9 mJ for acrylic IOL and 5.7 mJ for PMMA IOL. Damage to the IOL varied subjectively between IOL type, but there was no significant difference in number of defects caused, with the exception of high-medium energy. CONCLUSIONS: Both posterior lens capsules and IOLs were disrupted in an energy-dependent manner with minimal difference in number of capsulotomy sites or damage to the IOL between acrylic and PMMA IOLs. A therapeutic margin between capsulotomy threshold (2.6-2.7 mJ) and IOL damage threshold (4.9-5.7 mJ) was determined to reliably achieve capsulotomies with minimal IOL damage for both acrylic and PMMA IOLs in normal canine cadaver eyes.

Acrylates↗