Cerebroretinal vasculopathy, hereditary vascular retinopathy, and hereditary endotheliopathy, retinopathy, nephropathy and stroke are neurovascular syndromes initially described as distinct entities. Recently they were shown to be one disease caused by C-terminal frame-shift mutations in TREX1, which was termed 'retinal vasculopathy with cerebral leukodystrophy'. Here we defined the genetic and clinicopathologic spectrum of this clinically and pathophysiologically poorly characterized and frequently misdiagnosed fatal neurovascular disorder. We identified five different TREX1 mutations in 78 members from 11 unrelated families and by using a standardized study protocol we retrospectively reviewed and aggregated the associated clinical, neuroimaging, and pathology data. Findings were similar across mutations and families. Sixty-four mutation carriers had vascular retinopathy. Neuroimaging revealed (i) punctate, hyperintense, white matter lesions with or without nodular enhancement in 97% of them; (ii) rim-enhancing mass lesions in 84%; and (iii) calcifications in the white matter in 52%. Ninety per cent had clinical manifestations of brain disease, including focal neurological deficits (68%), migraine (59%), cognitive impairment (56%), psychiatric disturbances (42%), and seizures (17%). One mutation carrier had enhancing brain lesions and neurological features but unknown retinopathy status. Additional systemic features included liver disease (78%), anaemia (74%), nephropathy (61%), hypertension (60%), mild Raynaud's phenomenon (40%), and gastro-intestinal bleeding (27%). Mean (AE standard deviation) age at diagnosis was 42.9 AE 8.3 years and at death 53.1 AE 9.6 years. Pathological examination revealed systemic vasculopathy with luminal narrowing and multi-laminated basement membranes. The 13 mutation carriers without retinopathy or brain lesions were on average 8 years younger (mean age: 35.1 AE 10.6 years). Of them, 54% had mild Raynaud's phenomenon, 42% had migraine, and 23% had psychiatric disturbances. Retinal vasculopathy with cerebral leukodystrophy is an autosomal dominant systemic small-vessel disease due to specific TREX1 mutations and clinically primarily characterized by (i) visual impairment from vascular retinopathy; and (ii) neurological decline and premature death due to progressive enhancing cerebral white matter lesions. Impaired liver and kidney function, anaemia sometimes associated with gastrointestinal bleeding, hypertension, migraine, and Raynaud's phenomenon appear to be part of the clinical spectrum as well. Penetrance
The rate of endophthalmitis associated with intravitreal bevacizumab and ranibizumab is low, with an incidence of approximately 1 in 4,500 injections.
<h4>BACKGROUND AND OBJECTIVE</h4> <p>To evaluate the use of intravitreal pegaptanib in the treatment of choroidal neovascularization secondary to age-related macular degeneration (AMD) in treatment-naïve patients.</p> <h4>PATIENTS AND METHODS</h4> <p>In a consecutive, retrospective case series, treatment-naïve patients with exudative AMD were treated with intravitreal pegaptanib. Intravitreal injections were typically given every 6 weeks at the discretion of the treating physician. Snellen visual acuity (VA), clinical course, and adverse events were monitored. A minimum of three pegaptanib injections were given. Retreatment criteria included persistent submacular fluid, macular edema, new macular hemorrhage, and loss of vision.</p> <h4>RESULTS</h4> <p>The average change in VA for all lesions was a loss of 2.9 lines. Fifteen (14%) patients gained more than 3 lines of VA. The average number of injections was 4.8. Ninety-two of 111 lesions were able to be categorized by size. Sixty-six patients had small lesions (< 4 disc areas) with an average change of -2.0 lines, and 26 had large lesions (<span style="text-decoration: underline;">></span> 4 disc areas) with an average change of -5.4 lines (<em>P</em> < .02). Patients with larger lesions were at greater risk for severe visual loss (<em>P</em> < .01). The average follow-up was approximately 31 weeks (range: 12 to 82 weeks) after the first injection.</p> <h4>CONCLUSIONS</h4> <p>Pegaptanib therapy resulted in a 2.9 average line loss in patients when all lesions were considered. Small lesions responded favorably, with 15% of patients gaining more than 3 lines of VA. Larger lesions had an increased risk of progression and poor visual outcome.</p> <p>[<cite>Ophthalmic Surg Lasers Imaging</cite> 2007;38:371- 377.]</p> <h4>AUTHORS</h4> <p>From the Retina Service (CDR, MSF, ACH), Wills Eye Institute (JPE, DRF, OPG), Philadelphia, Pennsylvania.</p> <p>Accepted for publication April 30, 2007.</p> <p>Address correspondence to Allen C. Ho, MD, Retina Service, Wills Eye Institute, 840 Walnut Street, Suite 1020, Philadelphia, PA 19107.</p>
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