Department of Ophthalmology

Thomas Mauger, MD, Chair

The Department of Ophthalmology sees more than 60,000 patients a year, mostly in the William H. Havener Eye Institute at the Ohio State University Hospital Clinic in Cramblett Hall. The Department also has sites in Dublin and at Ohio State University Hospital East. Faculty are involved in multicenter clinical trials funded by the National Eye Institute, as well as by industry. Basic science studies include investigation of the biomechanical properties of the cornea and sclera, and fundamental studies of cerebral spinal fluid outflow facility and the impact on idiopathic intracranial hypertension. In addition, the Department’s Molecular Genetics Program studies uveal melanoma. Scientists are investigating the MET gene, which they believe is a crucial factor for the high selectivity of eye melanomas and other cancers that spread to the liver. They hope to identify molecular markers to monitor for metastatic disease. If they can identify at-risk patients, early intervention should lead to a better prognosis.

Ongoing Research Programs

Cornea:

Optical profilometry and atomic force microscopy analysis of corneal surface topography: the effect of lamellar keratoplasty, excimer laser ablation and smoothing procedures
Standard surface anterior surface topography measurements quantify the discrepancy between Scheimpflug and Placido-based topographers
Evaluation of the utility of intra-operative topography to optimize corneal shape during penetrating keratoplasty: a clinical trial examining whether topography-guided suture placement will improve surgical outcomes in corneal transplant patients
Corneal wound healing and artificial anterior chamber cultures: femtosecond laser and longterm corneal cultures – examination of the effect of state-of-the-art Femtosecond anterior and posterior Lamellar surgery techniques
Biomechanical and structural response of the cornea following Lamellar keratoplasty: an optical coherence tomography and Scheimpflug image analysis
High-resolution X-ray scattering analysis of the microfibril organization in cornea and optic nerve and its relation to biomechanical response
The study of central and peripheral corneal biomechanical response to swelling using topography, wave-front, viscoelastic properties and reflectivity coefficients in normal and LASIK populations

Glaucoma:

The Ocular Hypertension Treatment Study (OHTS) evaluates the efficacy of placing ocular hypertensive patients on eye drops to delay or perhaps prevent them from developing glaucoma.
The OHTS Ancillary Genetic Study collects blood from OHTS patients for a national database that may help identify glaucoma genetic markers.
The Memantine Study evaluates the effectiveness and safety of oral Memantine in patients with glaucoma who are at risk for progression of optic nerve damage.
Researchers are comparing the current standard post-glaucoma filtration surgery antiproliferative treatment, Mitomycin-c, to novel antiproliferative drugs and determining their effect on fibroblast and epithelial cell proliferation in an in vitro culture model.
To understand the mechanism of laser trabeculoplasty, which is wavelength independent and dependent on the rapid rate of temperature increase in the target tissue, with a total increase of less than 1°C, researchers are studying the irradiation- related functional relationships among the aqueous outflow pathway components, including the TM cells and the SCE cells using an in vitro model of the outflow pathway.

Neuro-Ophthalmology:

Scientists are studying a cerebral spinal fluid outflow mechanism through human arachnoid granulations using both in vitro and ex vivo models, including postperfusion ultrastructural studies using fluorescent microparticle perfusion, TEM and immunohistochemistry.
Scientists are working to understand the role of vitamin A and its cerebral spinal fluid (CSF) metabolites to support a novel mechanism of idiopathic intracranial hypertension (IIH), a well-controlled CSF and blood study of newly presenting IIH subjects.

Pediatrics:

In its sixth year of follow-up, the Early Treatment for Retinopathy of Prematurity trial continues to demonstrate the benefits of early treatment for high-risk prethreshold retinopathy of prematurity.
Corneal endothelium and ocular component change after strabismus surgery in children – this project investigates the influence of strabismus surgery on the corneal endothelial cells and ocular components in children.
Corneal endothelium change in type I diabetic children – This project investigates the influence of type I diabetes on corneal endothelial cells in children. It uses fMRI to explore normal and abnormal oculomotor function, as well as the neural basis of amblyopia and effects of pharmacological interventions. It also uses NIR (near infrared) to develop a test of visual function.

Retina:

Age-Related Macular Degeneration (AMD) – This program evaluated treatment modalities for patients suffering from AMD, the leading cause of vision loss in the United States for people over age 60. Scientists are involved in many new and exciting National Institutes of Health- and industry- sponsored studies that investigate treatments including anti-VEGF (vascular endothelial growth factor) drugs. Another study will look at prevention of this disease using a combination of dietary supplements and vitamin therapies. It will evaluate the potential for lutein and omega-3 fatty acid nutritional supplements to impede the progression of AMD.
Molecular Genetics – This program examines uveal melanoma. Researchers are focusing on the MET gene (also known as hepatocyte growth factor receptor), which they believe to be a crucial factor for the high selectivity of eye melanomas and other cancers that spread to the liver. They hope to identify molecular markers to monitor for metastatic disease. If they can identify at-risk patients, early intervention should lead to a better prognosis. We are collaborating with Cheryl London, DVM, PhD, a veterinary oncologist who is involved in target therapy using the MET gene.
Diabetic Retinopathy – Three clinical trials are ongoing in this program. One compares laser therapy and intravitreal drug therapy to determine which is more effective in treating diabetic macular edema (DME), the leading cause of vision loss in the ever-increasing diabetic population. A second trial evaluates the effect of panretinal laser therapy for diabetic retinopathy on the development of DME. A third trial strives to determine the effectiveness of optical coherence tomography to detect DME at a stage at which clinical observation alone may not. This could allow new strategies for prevention of vision loss in this common malady.
Choroidal Melanoma MRI – In collaboration with the Department of Radiology, Ophthalmology is imaging its melanoma patients with a 1.5 tesla MRI with dynamic contrast and surface coil imaging. This is a novel approach to evaluate the radiological perfusion characteristic of choroidal circulation. The goal is to discover predictive parameters of choroidal circulatory blood flow that may correlate with tumor size, rate of growth, metastases and survival.

Research Accomplishments of 2006

Glaucoma – The Ocular Hypertension Treatment Study (OHTS) is entering its 14th year; a measurement of visual contrast sensitivity and additional patient surveys have been included into the study. Researchers also continued to enroll patients in the OHTS ancillary genetic study and planned to complete it by June 2007. The Memantine Study concluded patient follow-up in summer 2006 and is in the final phase of data collection. The Glaucoma Division also initiated three studies: “Autoimmune Mechanisms in Giant Cell Arteritis”; “Autoimmune Mechanisms in Glaucoma”; and “Autoimmune Mechanisms in Graves’ Disease.” Each focuses on the discovery of an antibody that could cause these diseases. If identified, it could lead to earlier diagnosis and better treatment.
Pediatrics – Investigators clarified the differences between look (voluntary) Optokinetic Nystagmus (OKN) and stare (involuntary) OKN (ARVO 2006). Based on fMRI, they mapped brain areas responsible for pursuit and saccadic eye movements. They also pursued IRB approval of the near infrared multidisciplinary and multi-institutional research project.
Retina – The Department secured a role in the National Institutes of Health- and National Eye Institute-sponsored Age-Related Eye Disease Study 2 (AREDS 2 Study). Ohio State site was selected as one of nearly 100 centers to participate in the nationwide study to see if a modified combination of vitamins, minerals and fish oil can further slow the progression of vision loss from age-related macular degeneration, the leading cause of vision loss in the United States for people over age 60. The Department also was selected as one of 21 sites nationwide to participate in the Comparison of Age-related Macular Degeneration Treatments Trial (the CATT Study), which will evaluate the relative efficacy and safety of treatment of subfoveal, neovascular AMD with lucentis and avastin.
Neuro-Ophthalmology – Researchers demonstrated that both the in vitro and ex vivo human models of the cerebral spinal fluid (CSF) outflow pathway through the arachnoid granulations mimic the physiological unidirectional flow, in addition to the bulk flow component, via vacuole transport. This work was initially reported in the journal Investigational Ophthalmology & Visual Science and will be detailed in future publications. Scientists also demonstrated that the en face probability-ofoccurrence maps of human arachnoid granulations (AG) are localized in a characteristic distribution with regions of high and low probability. These measurements provide age-related surface area quantification data in terms of absolute values as well as proportional area with respect to total brain area. Total brain surface area declines with age and must be considered when analyzing proportional AG area. Race has a statistically significant effect on AG surface area, with Caucasians having a smaller proportion of positive area. Females have a smaller proportion of surface area in most age groups. This data will be used as input for an in vitro CSF perfusion model.
Jennifer Lewis, PhD, a U.S.-U.K. Fulbright Scholar in 2005-06, completed a research fellowship in the Structural Biophysics Laboratory at the School of Optometry and Vision Sciences, Cardiff University, Cardiff Wales and Guys, and the Department of Ophthalmology at St. Thomas’ Hospital in London. Her project was titled “Optical and X-ray studies of human and porcine cornea and the biomechanical response to Lamellar keratoplasty using femtosecond and mechanical microkeratome.”
Jennifer Wilding Bogucki, a third-year medical student, won first place at the fifth annual Ohio State University College of Medicine Graduate and PostGraduate Research Day for a poster entitled “Topographic data for normal donated human corneas.”
Andrew Schrader, an Ohio State University firstyear veterinary student, won the Deans’ Undergraduate Research Award to support his research. He also finished first in the Health Professions/Clinical Category at the Richard J. & Martha D. Denman Undergraduate Research Forum for a poster titled “Surface topography of the cornea following laser ablation with and without smoothing.”