A comparative effectiveness analysis of visual field outcomes after projected glaucoma screening using SD-OCT in African American communities.

PURPOSE: To assess the impact on visual function of community glaucoma screening in an African American population using spectral-domain optical coherence tomography (SD-OCT). METHODS: Using a Monte Carlo microsimulation model with a 10-year time horizon, we analyzed the efficacy of SD-OCT screening on visual field outcomes in a population of African Americans who are not otherwise seeking office-based care. Outcomes included classification of visual field severity, quality-adjusted life years, and direct health care costs. RESULTS: Assuming a 60% follow-up rate, screening decreased the prevalence of undiagnosed glaucoma from 75% to 38%, and decreased the prevalence of severe visual field loss in patients with glaucoma from 29.1% to 23.9%. Conversely, screening increased the prevalence of mild visual field loss in patients with glaucoma from 9.2% to 18.7%. From initial screening through confirmatory eye examination, the screening program ("screen only") cost $98 per screened individual, and $2561 per new diagnosis of glaucoma. When considering the costs of initial screening though the resultant treatment, the screening program ("screen and treat") had an average annual cost of $79 and $2138, respectively, over a 10-year time period. The cost of one quality-adjusted life year (QALY) gained by screening, including management and treatment, in comparison with opportunistic case finding, ranged from $46,416 to $67,813. CONCLUSIONS: Our findings suggest that community SD-OCT screening in an African American population will minimize glaucoma-related visual morbidity. Ideally, strategies to maximize treatment efficacy through improved medication adherence and improved compliance with follow-up should be identified and implemented before instituting a screening program.

Disease progression in autosomal dominant cone-rod dystrophy caused by a novel mutation (D100G) in the GUCA1A gene.

PURPOSE: To document longitudinal fundus autofluorescence (FAF) and electroretinogram (ERG) findings in a family with cone-rod dystrophy (CRD) caused by a novel missense mutation (D100G) in the GUCA1A gene. METHODS: Observational case series. RESULTS: Three family members 26-49 years old underwent complete clinical examinations. In all patients, funduscopic findings showed intraretinal pigment migration, loss of neurosensory retinal pigment epithelium, and macular atrophy. FAF imaging revealed the presence of a progressive hyperautofluorescent ring around a hypoautofluorescent center corresponding to macular atrophy. Full-field ERGs showed a more severe loss of cone than rod function in each patient. Thirty-hertz flicker responses fell far below normal limits. Longitudinal FAF and ERG findings in one patient suggested progressive CRD. Two more advanced patients exhibited reduced rod response consistent with disease stage. Direct sequencing of the GUCA1A gene revealed a new missense mutation, p.Asp100Gly (D100G), in each patient. CONCLUSION: Patients with autosomal dominant CRD caused by a D100G mutation in GUCA1A exhibit progressive vision loss early within the first decade of life identifiable by distinct ERG characteristics and subsequent genetic testing.

Minimalist model for force-dependent DNA replication.

In experiments using optical or magnetic tweezers, investigators have monitored the rate at which polymerase enzymes catalyze DNA replication when the template strand is subjected to a stretching force. For T7, Klenow, and Sequenase polymerases, the replication rate increases modestly at low tension and then decreases markedly at higher tension. Molecular-dynamics (MD) simulations using x-ray structure data for the open and closed complexes of the Taq enzyme with DNA revealed that the dependence of replication rate on tension could be accounted for in terms of the induced enthalpy changes for the two DNA segments adjacent to the site of the added nucleotide. Here, we present a simple, minimalist two-segment local model (M2L) derived from some striking features seen in the MD simulations. The model predicts the tension dependence of the replication rate using only structural data and a critical tension, f(∗), without recourse to MD simulations. At f(∗), the outermost DNA segment undergoes a large angular reorientation in the open conformation of the enzyme. We give a generic plot for the M2L model, apply it to family A and B polymerases and HIV reverse transcriptase, and discuss factors that may govern the f(∗) flip parameter.

Biopolymer-released dexamethasone prevents tumor necrosis factor alpha-induced loss of auditory hair cells in vitro: implications toward the development of a drug-eluting cochlear implant electrode array.

HYPOTHESIS: Polymer-eluted dexamethasone (DXM) will retain its ability to protect against tumor necrosis factor alpha (TNFalpha)-induced hair cell (HC) loss. BACKGROUND: TNFalpha has been shown to be associated with trauma-induced hearing loss. DXM has been demonstrated to protect the cochlea against trauma-induced hearing loss. DXM is currently administered either systemically or locally to treat patients with sudden hearing loss of unknown cause. METHODS: P-3 organ of Corti explants challenged with an ototoxic level of TNFalpha was the experimental system, and the base form of DXM (DXMb) incorporated into a biorelease polymer (i.e., SIBS) was the otoprotection molecule tested. The efficacy of otoprotection was determined by counts of fluorescein isothiocyanate-phalloidin-stained HCs and changes in gene expression. RESULTS: HC counts show 1) SIBS alone did not protect HCs from TNFalpha ototoxicity (SIBS versus SIBS + TNFalpha; p < 0.001), and 2) SIBS with DXMb provides a significant level of protection against TNFalpha-induced loss of HCs (TNFalpha + SIBS versus TNFalpha + SIBS/DXMb, 299 mug; p < 0.001). Gene expression results show that polymer-eluted DXMb 1) upregulates antiapoptotic genes (i.e., Bcl-2, Bcl-xl) and downregulates a proapoptotic gene (i.e., Bax) in TNFalpha-challenged explants and 2) downregulates TNFR1 in these explants. CONCLUSION: Polymer-eluted DXMb retains its otoprotection capabilities in our in vitro test system of TNFalpha-challenged organ of Corti explants by altering the pattern of gene expression to favor survival of TNFalpha-exposed HCs. These results, although in vitro, support the application of polymer containing DXMb to electrode arrays for the conservation of hearing during cochlear implantation.