Showing papers by "Pratap Challa published in 2014"

Rho-kinase inhibitors offer a new approach in the treatment of glaucoma

Abstract: Introduction: Primary open-angle glaucoma (POAG) is a leading cause for worldwide blindness and is characterized by progressive optic nerve damage. The etiology of POAG is unknown, but elevated intraocular pressure (IOP) and advanced age have been identified as risk factors. IOP reduction is the only known treatment for glaucoma. Recently, drugs that inhibit rho-associated protein kinase (ROCK) have been studied in animals and people for their ability to lower IOP and potentially treat POAG. ROCK inhibitors lower IOP through a trabecular mechanism and may represent a new therapeutic paradigm for the treatment of POAG. Areas covered: Exploring the place that ROCK inhibitors may occupy in our treatment of POAG requires a thorough understanding of pathophysiology and treatment. This article summarizes current research on the incidence, proposed etiologies and mechanisms of action for this drug class. ROCK inhibitor research is presented and considered in light of the current standard of pharmacologic care. E...

Osteogenesis imperfecta and primary open angle glaucoma: Genotypic analysis of a new phenotypic association

Abstract: Purpose: Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by bone fragility. Ocular findings include blue sclera, low ocular rigidity, and thin corneal thickness. However, there are no documented cases linking OI and primary open angle glaucoma (POAG). In this report, we describe three individuals, one isolated case and two from a multiplex family, with OI type I and POAG. Methods: Available family members with OI and POAG had a complete eye examination, including visual acuity, intraocular pressure (IOP), pachymetry, slit-lamp exam, dilated fundus exam, and visual fields. DNA from blood samples was sequenced and screened for mutations in COL1A1/2 and myocilin (MYOC). Results: All subjects had OI type I. Findings of POAG included elevated IOP, normal gonioscopy, and glaucomatous optic disc cupping and visual field loss. POAG cosegregated with OI in the multiplex family. The multiplex family had a single nucleotide insertion (c.540_541insC) in COL1A1 resulting in a frameshift mutation and a premature termination codon. The sporadic case had a COL1A1 splice acceptor site mutation (c.2452–2A>T or IVS36–2A>T) predicted to result in a premature termination codon due to intron inclusion or a cryptic splice site. None of the glaucoma cases had mutations or sequence changes in MYOC. Conclusions: We identified two novel mutations in COL1A1 in individuals with OI type I and POAG. Thus, some mutations in COL1A1 may be causative for OI and POAG. Alternatively, susceptibility genes may interact with mutations in COL1A1 to cause POAG.

Osteogenesis Imperfecta and the Eye

Abstract: While the many skeletal, auditory, dental and other anomalies in osteogenesis imperfecta (OI) have been well documented in the medical literature, the eye and the visual system are also commonly affected in patients with OI. As type I collagen fibers are also found in ocular structures including the cornea and sclera, eyes in OI patients may have corneal thinning and blue sclerae to different degrees related to the severity of altered type I collagen synthesis as a result of OI. More severe ocular and visual system problems may also be related to OI and lead to significant visual impairment. Ocular and visual pathway problems reported in OI patients include corneal disorders, glaucoma, retinal detachment, optic neuropathy and others. This chapter provides an overview of the range of eye and vision-related pathologies found in patients with OI. This chapter (1) reviews the basic anatomy of the eye and visual system for background, (2) provides a literature review of case reports, case series and clinical studies that relate to the eye and visual pathways in OI, (3) shares results from an eye survey of OI patients from the Kennedy Krieger Institute and (4) makes general recommendations regarding eye care for OI patients.