Faculty Bibliography

Background: Recent studies have suggested that vascular endothelial growth factor (VEGF) is an important stimulus for the growth of new blood vessels in the eye. Anti-VEGF therapy is thus a potential treatment for exudative macular degeneration and diabetic retinopathy. Methods: Previously described animal models of vascular leakage and ocular neovascularization, including the Miles assay, the rat corneal angiogenesis model, and the mouse retinopathy of prematurity (ROP) model, were used to study this drug. After these studies, a phase IA single ascending dose study of intravitreal injections of the drug was performed in 15 patients with subfoveal choroidal neovascularization secondary to exudative age-related macular degeneration (AMD). Results: The Miles assay model showed almost complete attenuation of VEGF-mediated vascular leakage following addition of EYE001, and the corneal angiogenesis model also showed a significant reduction in neovascularization with EYE001. The ROP model showed inhibition of 80% of the retinal neovascularization compared with controls (P = 0.0001). The phase A safety study of patients with exudative AMD showed no significant safety issues related to the drug. Ophthalmic evaluation revealed that 80% of patients showed stable or improved vision 3 months after treatment and that 27% of eyes demonstrated a three-line or greater improvement in vision on the Early Treatment for Diabetic Retinopathy Study chart at this time. Conclusion: Anti-VEGF therapy is a promising new avenue for the treatment of neovascular diseases of the eye, including exudative macular degeneration and diabetic retinopathy. Preclinical data from studies with EYE001 support clinical evaluation of its efficacy in such diseases. This report is the first to describe administration of anti-VEGF therapy in humans for exudative macular degeneration and shows the safety of such therapy for single injections. Further clinical studies are necessary to determine the safety of multiple intravitreal injections of EYE001 and larger studies are needed to prove the efficacy of this novel, potentially therapeutic agent for neovascular AMD

PURPOSE: To determine if oral hydration decreases the incidence of verteporfin infusion-associated pain and to find out if other factors play a role in predisposing to this undesired complication. METHODS: Nonrandomized clinical trial. We prospectively examined 250 consecutive patients who have been diagnosed with subfoveal choroidal neovascularization secondary to age-related macular degeneration and received photodynamic therapy using verteporfin. One hundred twenty-five patients were assigned to receive 500 ml of water orally administered 30 minutes before beginning the verteporfin infusion, and the remaining 125 consecutive patients were used as controls. Historical and clinical factors in these patients were evaluated for their association with the presence of verteporfin infusion-associated pain. RESULTS: Out of 125 patients receiving water before treatment 12 (9.6%) experienced verteporfin infusion-associated pain. Among the 125 patients who did not get hydration before therapy 12(9.6%) experienced verteporfin infusion-associated pain. There was no statistical difference between the incidence of pain in the two groups (P = 1.0). No statistically significant association was evidenced between the presence of pain and participant's baseline characteristics, except for pain on previous administration of verteporfin (P < .001). Out of 250 total patients 24 (9.6%) developed verteporfin infusion-associated pain. Back pain was the most common and occurred in 21 (8.4%) patients, but other sites included leg, groin, chest, buttock, arm, and shoulder pain concurrently or independently. All patients had resolution of their pain, including chest pain, on cessation of the infusion. CONCLUSIONS: Verteporfin infusion-associated pain may be more common than has been previously reported and is not limited to the back area. It appears to be an idiosyncratic reaction to the drug. It does not seem to be prevented by oral hydration before infusion of verteporfin, and no baseline characteristics, other than a history of pain on previous infusion, seem to be predictive of verteporfin infusion-associated pain

OBJECTIVE: To describe a case of a patient with documented genetic mallatia leventinese who developed a classic choroidal neovascular membrane and underwent photodynamic therapy (PDT) with verteporfin (Visudyne; CIBA Vision Corp., Duluth, GA). DESIGN: Interventional case report. INTERVENTION: The patient underwent a complete ophthalmologic evaluation and fluorescein angiography. Photodynamic therapy with verteporfin was performed. MAIN OUTCOME MEASURES: Clinical and angiographic records were analyzed for evidence of changes in visual acuity, clinically evident subretinal fluid and the extent of fluorescein leakage from choroidal neovascularization (CNV). RESULTS: Three weeks after treatment, a fluorescein angiogram showed closure of the neovascular membrane, no evident subretinal fluid was seen, and visual acuity had improved from 20/60- to 20/40. Nine weeks after the application, fluorescein angiography demonstrated a microscopic hyperfluorescent spot at the site of the previously active CNV at which a small area of shallow subretinal fluid was observed, and visual acuity was 20/50. Thirty-four weeks after PDT, visual acuity was 20/60, subretinal fluid resolved, and fluorescein angiography did not show any further changes. CONCLUSIONS: Photodynamic therapy with verteporfin may be considered as a possible treatment in patients with mallatia leventinese who develop classic CNV

OBJECTIVE: To describe clinical and angiographic features of patients with central serous chorioretinopathy (CSC) who had yellowish subretinal deposits forming a reticulated leopard-spot pattern during fluorescein angiography. METHODS: We conducted case studies using the clinical and photographic records of 5 patients. RESULTS: All 5 patients were older men between the ages of 68 and 81 years who had been treated with corticosteroids and had bilateral CSC. Nine eyes of the 5 patients developed yellowish deposits in a reticulated pattern in the macular region under the chronic detached neurosensory retina. The pattern of leopard-spot deposits was well demonstrated on the fluorescein angiogram, with hypofluorescence in most of the deposits and hyperfluorescence from atrophy of the retinal pigment epithelium. Later phases of the fluorescein angiographic study showed leaks from the retinal pigment epithelium. During the indocyanine green angiography evaluation of 4 patients, all had bilateral multifocal patches of hyperfluorescence in the midphase, findings typical of CSC. CONCLUSIONS: Yellowish deposits forming a reticulated leopard-spot pattern may occur under the neurosensory retina and are associated with chronic neurosensory detachment caused by CSC. All patients were older men being treated with corticosteroids. This report described a newly recognized finding: the subretinal deposition of a yellowish material in a leopard-spot pattern in eyes with CSC

PURPOSE: Whipple's disease is a rare, chronic, and multiorgan bacterial disease that predominantly involves the gut and its lymphatic drainage in middle-aged Caucasian men but may involve the eye. It is often difficult to diagnose and treat. We report results of one more polymerase chain reaction (PCR) analysis-diagnosed ocular Whipple's disease (OWD) case and the care of three new patients with ocular inflammation caused by OWD. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Three patients. METHODS: Diagnostic PCR was performed on a vitreous sample, medical records of three patients with OWD were reviewed, and a literature review (1907 to present) located 74 OWD cases. Analysis of published OWD cases to seek out factors that contribute to earlier, definitive diagnosis and treatment of OWD is made. MAIN OUTCOME MEASURES: Response of ocular inflammation and vision to treatment. RESULTS: One of 3 new and 4 of 74 published OWD cases reviewed were diagnosed with PCR on vitreous samples and subsequently successfully treated with antibiotics without devastating central nervous system (CNS) sequelae. CONCLUSION: Diagnostic PCR on vitreous samples and recognition of key presenting symptoms in patients with OWD allows earlier definitive diagnosis, when the disease may be more amenable to antibiotic treatment, compared with 'late' CNS Whipple's disease in the cases reviewed

PURPOSE: To report three patients who developed central serous chorioretinopathy after epidural corticosteroid injection for treatment of back pain. DESIGN: Interventional case series. METHODS: Three men, aged 73, 52, and 73 years, presented with bilateral central serous chorioretinopathy after corticosteroid injection in the epidural space for treatment of back pain. In all three cases, we did not initially elicit the history of corticosteroid use. RESULTS: Two of the three patients, aged 52 and 73 years, had diffuse retinal pigment epitheliopathy and one, aged 73 years, had classic central serous chorioretinopathy. Two patients had a spontaneous resolution of the subretinal fluid in both eyes. One patient had laser photocoagulation in both eyes but continued to have diffuse leakage in one eye. CONCLUSIONS: A careful history to determine corticosteroid use, including possible intrajoint and epidural injection, should be performed in older people with serous detachment of the macula, particularly when bilateral

Objective: To evaluate the relationship between intake of total and specific types of fat and risk for advanced age-related macular degeneration (AMD), the leading cause of irreversible blindness in adults. Design: A multicenter eye disease case-control study Setting: Five US clinical ophthalmology centers. Patients: Case subjects included 349 individuals (age range, 55-80 years) with the advanced, neovascular stage of AMD diagnosed within 1 year of their enrollment into the study who resided near a participating clinical center. Control subjects included 504 individuals without AMD but with other ocular diseases. Controls were from the same geographic areas as cases and were frequency-matched to cases by age and sex. Main Outcome Measures: Relative risk for AMD according to level of fat intake, controlling for cigarette smoking and other risk factors. Results: Higher vegetable fat consumption was associated with an elevated risk for AMD. After adjusting for age, sex, education, cigarette smoking, and other risk factors, the odds ratio (OR) was 2.22 (95% confidence interval [ CI] 1.32-3.74) for persons in the highest vs those in the lowest quintiles of intake (P for trend, .007). The risk for AMD was also significantly elevated for the highest vs lowest quintiles of intake of monounsaturated (OR, 1.71) and polyunsaturated (OR, 1.86) fats (Ps for trend, .03 and .03, respectively). Higher consumption of linoleic acid was also associated with a higher risk for AMD (P for trend, .02). Higher intake of omega -3 fatty acids was associated with a lower risk for AMD among individuals consuming diets low in linoleic acid, an omega -6 fatty acid (P for trend, .05; P for continuous variable,.03). Similarly, higher frequency of fish intake tended to reduce risk for AMD when the diet was low in linoleic acid (P for trend, .05). Conversely, neither omega -3 fatty acids nor fish intake were related to risk for AMD among people with high levels of linoleic acid intake. Conclusion: Higher intake of specific types of fat-including vegetable, monounsaturated, and polyunsaturated fats and linoleic acid-rather than total fat intake may be associated with a greater risk for advanced AMD. Diets high in omega -3 fatty acids and fish were inversely associated with risk for AMD when intake of linoleic acid was low. $$: