Frank W. Scribbick

Topical Voriconazole as a Novel Treatment for Fungal Keratitis

ABSTRACT Paecilomyces lilacinus is a fungal pathogen which is generally resistant to amphotericin B and certain other antifungals and is an uncommon cause of devastating fungal keratitis. In the present studies, we evaluated topical voriconazole as therapy for P. lilacinus keratitis in rabbits. Thirty eyes of 15 rabbits were studied. In five animals, the uninfected left eye was treated twice daily with voriconazole (drug control, uninfected eye). In these same animals, the right eye was infected with P. lilacinus but not treated with voriconazole (infection control eye). By day 5, the infection controls had lesions of >2.4 mm in diameter, with conjunctivitis and severe hypopyon, and were sacrificed. In the other 10 rabbits (voriconazole treatment), the right eyes were infected with P. lilacinus and treated with voriconazole beginning on day 3 after infection. Voriconazole therapy caused lesions to decrease during 8 days of therapy, after which rabbits were sacrificed (11 days postinfection). Hyphal masses were present in the control infected eyes and absent in treated infected eyes. Voriconazole was detected in all tissues of treated eyes. Topical voriconazole is effective treatment for P. lilacinus experimental keratitis, and it penetrates more deeply than the corneal tissue.

Use of Bioglass for Orbital Volume Augmentation in Enophthalmos: A Rabbit Model (Oryctolagus Cuniculus)

Purpose To investigate the clinical and histologic response of Novabone-C/M as an osteoproductive alloplastic implant for volume augmentation in the orbit in the treatment of enophthalmos and to compare its outcome alone versus its use in combination with autogenous bone or Medpor granules. Methods Novabone-C/M, a bioactive silicone glass material, was implanted in the subperiosteal space of the left orbit of 12 New Zealand White rabbits. The animals were divided into 3 groups, each with 4 animals, based on the material implanted in the orbit: group 1, Novabone alone; group 2, Novabone plus Medpor granules; and group 3, Novabone plus autogenous bone fragments. All rabbits were studied clinically, radiographically, and histologically at 1-, 3-, and 6-month intervals. Animals underwent preoperative and postoperative computed tomography (CT) with 3-dimensional reconstruction, proptosis measurements, and volumetric analysis. Orbit specimens were studied histologically with mineralized bone stain (MIBS) to look for bone formation, reactivity, infection, implant resorption, and migration. Results There were no signs of significant inflammation or infection. Subcutaneous migration of the implant was seen radiographically but not clinically in groups 1 and 3. Induced proptosis averaged 2.5 mm (at 1 month) and showed regression in all groups over a 6-month period but was not statistically significant. Implant volume was markedly reduced in all groups, averaging 69% in group 1, 37% in group 2, and 59% in group 3 at 6 months. New bone formation and bone remodeling was present in all 3 groups at 3 months and only in group 2 at 6 months. The rate and amount of implant remodeling and bone formation was greatest in the Novabone/Medpor group (group 2). Conclusions Bioglass particulate is biocompatible, easy to use in the orbit, and stimulates bone growth. Bioglass is associated with volume loss and migration over 6 months and may not provide adequate volume augmentation in the orbit when used alone for the treatment of enophthalmos. The duration and amount of bone formation may be enhanced when Novabone is used in conjunction with Medpor.

Blunt eye trauma: Empirical histopathologic paintball impact thresholds in fresh mounted porcine eyes

PURPOSE Ballistic studies were conducted using gelatin-embedded abattoir-fresh porcine eyes suspended within clear acrylic orbits to discern the energy required to produce specific ocular injuries. Paintball impact provides a robust ballistic model for isolating and quantifying the role of direct blunt force in ocular trauma. METHODS Fifty-nine porcine orbital preparations received direct blows from 0.68 caliber (16-18 mm diameter/3.8 g) paintballs fired at impact velocities ranging from 26 to 97 meters per second (2-13.5 J). Five additional eyes not subjected to ballistic impact were also evaluated as controls. Impact energies were correlated with histopathologic damage. RESULTS Minimum impact energies consistently producing damage in experimental eyes unobserved in control specimens were: 2 joules--posterior lens dislocation, zonulysis, capsular rupture, and choroidal detachment; 3.5 joules--moderate angle recession; 4 joules--anterior lens dislocation; 4.8 joules--peripapillary retinal detachment; 7 joules--severe angle recession, iridodialysis, and cyclodialysis; 7.5 joules--corneal stromal distraction; 9.3 joules--choroidal segmentation; and 10 joules--globe rupture. CONCLUSIONS Impact thresholds correlating traumatic ocular pathology with impact energy followed a positive stepwise progression in severity with impact energies between 2 and 10 joules. Moderate angle recession commensurate with typical clinical traumatic glaucoma was not observed among control eyes, but occurred at relatively low impact energy of 3.5 joules among test eyes. Extensive disruption in and around the angle (iridodialysis/cyclodialysis) consistently occurred at energies >7 joules. Globe rupture required a minimum energy of 10 joules.

Effect of Topical Immunomodulatory Interleukin 1 Receptor Antagonist Therapy on Corneal Healing in New Zealand White Rabbits (Oryctolagus cunniculus) After Photorefractive Keratectomy

OBJECTIVES To compare topical interleukin 1 receptor antagonist (IL-1ra) to steroid treatment following photorefractive keratectomy (PRK) in rabbit eyes. METHODS Our study is a randomized, investigator-masked study that was approved by the Institutional Animal Care and Use Committee. Following standard PRK, 48 eyes of 24 rabbits were divided into 5 arms: 4 treatment arms and 1 control arm. The right eye of each rabbit served as the treatment eye, and the left eye served as a control. Eyes in treatment arms were randomized to receive either fluorometholone, 0.1%, 4 times a day (Falcon, Fort Worth, Texas), or 2.5, 1.25, or 0.25 mg of IL-1ra 4 times a day. Control eyes received only moxifloxacin hydrochloride, 0.5% (Vigamox; Alcon, Fort Worth, Texas), and a solution of polyethylene glycol 400, 0.4%, and propylene glycol, 0.3% (Systane; Alcon), 4 times a day. Primary outcome measures included weekly evaluation of subjective haze formation and time to corneal reepithelization with clinic examinations, objective haze formation using Pentacam technology (Oculus, Lynnwood, Washington), as well as histological examination for haze thickness 7 weeks after PRK. RESULTS There was no difference among treatment groups in time to reepithelization. The IL-1ra treatment groups showed a statistically significant reduction in haze formation (P < .001, determined by repeated-measures analysis of variance) on corneal evaluation using the Pentacam 3 weeks after PRK compared with the control group. This effect was comparable to that in the steroid treatment group. There was also a statistically significant effect of the treatment on subjective haze evaluation at weeks 4 and 5 (P < .05, determined by repeated-measures analysis of variance), but this effect lost statistical significance when the steroid group was excluded from the evaluation. In addition, there was no statistically significant difference in histologic evaluation of haze thickness among treatment groups (P = .997). CONCLUSION Further studies are needed to determine the efficacy and adverse effect profile of topical IL-1ra in human eyes. CLINICAL RELEVANCE IL-1ra therapy may be an alternative to steroid treatment following PRK.

Pathologic evaluation of radial optic neurotomy in an animal model

Vascular endothelial growth factor plays an important role in the development of abnormal blood vessels in proliferative diabetic retinopathy and other retinovascular diseases.1 Intravitreal administration of bevacizumab (Avastin, Genentech, Inc., San Francisco, CA), a humanized monoclonal antibody to vascular endothelial growth factor, has recently been reported to be of benefit in macular degeneration.2,3 This case report demonstrates the rapid resolution of iris and retinal neovascularization in a diabetic patient after the intravitreal injection of bevacizumab.

Plasminogen deficiency as a rare cause of conjunctivitis and lymphadenopathy

Plasminogen deficiency is a rare disorder complicated by the subsequent formation of firm “woody” plaques in the eye (ligneous conjunctivitis) or other mucosal sites as the result of inflammation or trauma. The plaques are composed of fibrinogen, granulation tissue, and inflammatory cells. The findings may be considered nonspecific by the unsuspecting surgical pathologist and delay the appropriate diagnosis. We report the first case of lymph node involvement with characteristic eosinophilic hyaline deposits that are periodic acid Schiff positive, stain dark red with Masson trichrome, and contain fibrinogen as detected by immunofluorescence and describe the longitudinal evolution of this patients disease over a 15-year period. The differential diagnosis of amorphous hyaline material in lymph node biopsies is discussed.