Roger Turbin, MD, assistant professor of ophthalmology, UMDNJ-New Jersey Medical School; associate director of neuro-ophthalmology and director of ocular trauma, UMDNJ-University Hospital

As a young faculty member, the direction of my early research was influenced by close relationships with my two previous fellowship preceptors, Mark Kupersmith and Jack Kennerdell at New York University and Allegheny General Hospital. Their guidance provided a platform on which to expand into areas of my own research. Both physicians emphasized the importance of a team approach to neuro-ophthalmic and surgical orbital disease, a tradition I have continued.

My interactions with colleagues in diagnostic and interventional subspecialties have provided me with unique challenges for both clinical practice and research. Traditionally, physicians are taught to develop practice patterns rooted in large study populations, preferably based on thousands of patients. Yet, many of the diseases I care for occur too rarely to support large studies and are more closely akin to unusual "orphan diseases." Even the largest and most well controlled prospective interventional trial for optic neuritis, one of the most common diseases I see, enrolled only 457 patients over three years. Similarly, most clinical studies in our field, although multi-institutional, are based on summaries of far fewer than 100 cases. Yet, ophthalmologists seem to make important progress with such limited resources. For instance, a handful of centers treating retinoblastoma in the U.S. has transformed a uniformly fatal and blinding disease of childhood into one associated with childhood survival and retention of excellent sight in at least one eye.

My current research includes a two-year open-label, multi-institutional study, to treat the unaffected eyes of patients with Leber's hereditary optic neuropathy presenting with first eye visual loss. The disorder, which primarily affects young men, is the phenotypic expression of a hereditary mitochondrial DNA mutation. Affected males suffer irreversible, sequential sudden visual loss in both eyes, typically between the ages of 20 and 40. The study was designed to prospectively assess the ability of a neuro-protective drug to change the course of visual loss in the second eye, which historically develops visual loss within months of the first eye involvement. Prior to the study enrollment closure, more than 40 national sites enrolled fewer than 10 patients with this rare disease. Fortunately, I was able to enroll a patient who met the criteria and our work has significantly contributed to the outcome of this study, and, I hope, to our understanding of the disease process.

Enlarge the image Figure 1. Schematic diagram describing cutaneous zones of entry, based on pattern of occult penetrating intracranial injury. Zones 1 and 2 represent nonmedial superior and inferior entry points. Zone 3 with subdivisions represent medial entry points. Zone 4 represents all non-medial entry points.

Similarly, some of the work that I began with Jack Kennerdell on optic nerve sheath meningioma resulted in a publication of a paper in the May 2002 issue of Ophthalmology, which has helped define the current standard of care for vision-preserving therapy in patients with this tumor. Optic nerve sheath meningioma (ONSM) is a neoplastic tumor of the optic nerve sheath which has a predilection for affecting young, healthy women. However, it may also affect subjects of any age, and is particularly aggressive in children. The tumor causes visual loss by compression of the optic nerve, and may result in associated damage to other important local structures. We published the outcome of patients treated using various modalities, including observation, surgery, and radiotherapy. Work in subgroups of these patients continues, and results were presented at the Academy of Ophthalmology, as well as in the Yearbook of Ophthalmology, 2003.

Enlarge the image Figure 2: Simulated model skull with porcine eyes placed in anatomic position, supported by lipid vegetable shortening to simulate orbital fat.

We observed the following results: 58 patients had unilateral and six patients had bilateral disease; none had neurofibromatosis. Thirteen patients were only observed, 12 only had surgery, 18 received radiation alone, and 16 had surgery and radiation. Two patients received resection and radiation. Irradiated patients received 4,000-5,500 cGy of conventional multiport or conformal external beam therapy, typically fractionated over six weeks. Patients with ONSM receiving radiation alone demonstrated the best visual outcome during the period of follow-up. We recommended that fractionated external beam radiation (5,000-5,500 cGg) be considered as initial treatment in adults in selected cases when preservation of visual function is a reasonable therapeutic goal.

Enlarge the image Figure 3: Helical CT accurately detects small glass fragments in anterior and posterior intraocular chambers.

Another interesting project involves the development of a system of classification that will help to predict patterns of intracranial injury occurring in the setting of occult penetrating transcutaneous orbito-cranial injury based on suspected cutaneous entry sites. We analyzed all published cases spanning the time period of modern radiographic imaging (1980-2002) to determine common types of injury. Analysis of recurring patterns led to the development of a classification system that helps predict intracranial extension from superficial wounds, thereby providing a guideline for more timely and accurate diagnosis and treatment of such cases. For the purpose of describing trends, the orbit was divided into four zones (Figure 1). Perforation of the orbital roof with injury to the frontal lobe was the most commonly observed injury (60% of cases). The majority of these entered via upper or lower non-medial eyelid or conjunctival lacerations. The second most frequent pattern of injury in our study involved penetration of the superior orbital fissure into the cavernous sinus, temporal lobe, or prepontine cistern. Such injuries were related to entry points at the medial orbit or canthal region in 83.3% of cases.

We also recently evaluated the efficacy of computerized tomography (CT), magnetic resonance imaging (MRI), and ultrasonography (US), to detect intraocular glass, varying in size, placed at three locations in the globe, using a simulated model of the human eye, orbital fat and cranium (Figures 2, 3). We utilized a standard radiographic model of the skull, and placed fresh porcine eyes within a bed of vegetable fat to simulate the in vivo conditions. Detection rates were 57.14% for helical CT, 27% for axial CT, and 11.11% for T1 MRI. Detection rates for glass fragment size ranged from 91.67% at 1.5 mm to 48.29% at 0.5 mm, significant at P<0.0001. Helical CT was the most sensitive imaging modality for the detection of intraocular glass. The sensitivity of detection was unaffected by hyphema (blood placed within the animal eye anterior chamber) and varied with the type of glass, size and location.

Roger Turbin, MD, is the associate director of neuro-ophthalmology and director of ocular trauma at UMDNJ-University Hospital and is assistant professor of ophthalmology at UMDNJ-New Jersey Medical School. Dr. Turbin attended the Washington University School of Medicine. He completed his residency in ophthalmology at New York University/Bellevue, and fellowships in neuro-ophthalmology and orbital surgery at The Institute for Neurology and Neurosurgery in New York and Allegheny General Hospital in Pittsburgh. Dr. Turbin's research interests include orbital tumors, inflammatory conditions and trauma, as well as unusual diseases of the optic nerve.§