We describe an automated method to locate the optic nerve in images of the ocular fundus. Our method uses a novel algorithm we call fuzzy convergence to determine the origination of the blood vessel ...network. We evaluate our method using 31 images of healthy retinas and 50 images of diseased retinas, containing such diverse symptoms as tortuous vessels, choroidal neovascularization, and hemorrhages that completely obscure the actual nerve. On this difficult data set, our method achieved 89% correct detection. We also compare our method against three simpler methods, demonstrating the performance improvement. All our images and data are freely available for other researchers to use in evaluating related methods.
Describes an automated method to locate and outline blood vessels in images of the ocular fundus. Such a tool should prove useful to eye care specialists for purposes of patient screening, treatment ...evaluation, and clinical study. The authors' method differs from previously known methods in that it uses local and global vessel features cooperatively to segment the vessel network. The authors evaluate their method using hand-labeled ground truth segmentations of 20 images. A plot of the operating characteristic shows that the authors' method reduces false positives by as much as 15 times over basic thresholding of a matched filter response (MFR), at up to a 75% true positive rate. For a baseline, they also compared the ground truth against a second hand-labeling, yielding a 90% true positive and a 4% false positive detection rate, on average. These numbers suggest there is still room for a 15% true positive rate improvement, with the same false positive rate, over the authors' method. They are making all their images and hand labelings publicly available for interested researchers to use in evaluating related methods.
To evaluate the efficacy of a second year of pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD).
Two concurrent, multicenter, randomized, double-masked, ...sham-controlled studies (V.I.S.I.O.N. Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization trials).
Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102.
At week 54, those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 pegaptanib doses.
Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of > or =15 letters from week 54 to week 102; losing <15 letters (responders) from baseline to week 102; gaining > or =0, > or =1, > or =2, and > or =3 lines of VA; and progressing to legal blindness (20/200 or worse).
In combined analysis, mean VA was maintained in patients continuing with 0.3-mg pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg pegaptanib for a second year were less likely to lose > or =15 letters than those re-randomized to discontinue after 1 year (P<0.05). The proportion of patients gaining vision was higher for those assigned to 2 years of 0.3-mg pegaptanib than receiving usual care. Progression to legal blindness was reduced for patients continuing 0.3-mg pegaptanib for 2 years.
Continuing visual benefit was observed in patients who were randomized to receive therapy with pegaptanib in year 2 of the V.I.S.I.O.N. trials when compared with 2 years' usual care or cessation of therapy at year 1.
Age-related macular degeneration (AMD) is a leading cause of visual impairment in aging populations in industrialized countries. Here we investigated whether the genotype of vascular endothelial ...growth factor A (VEGFA) gene is associated with response to anti-VEGF therapy. 223 eyes with neovascular AMD were treated with intravitreal anti-VEGF therapy. Responders were defined as patients who had an improvement in best corrected visual acuity (BCVA) of at least 5 letters or one line on the EDTRS visual acuity chart along with resolution of intraretinal or subretinal fluid over 12 months. Patients who did not meet the definition of responders were classified as poor-responders. The vision of responders (n = 148) improved while the vision of poor-responders (n = 75) worsened (P<0.001). Responders on average had a decrease in central foveal thickness (CFT), while poor-responders had an increase in CFT (P <0.001). Compared with the responder group, the poor-responder group had a higher frequency of the risk (T) allele (Allelic P = 0.019) and TT genotype (P = 0.002 under a recessive model) for the VEGFA-rs943080 polymorphism. VEGFA expression was 1.8-fold higher in cells with the VEGFA rs943080 TT genotype than in cells with the VEGFA rs943080 CC genotype (P = 0.012). Age, gender, smoking, diabetes mellitus, and hypertension did not play a significant role in treatment response, but BMI was found to be significantly different between responders and poorresponders (P = 0.033). In conclusion, we demonstrated a potential pharmacogenetic relationship between the VEGFA gene and treatment response to anti-VEGF therapy.The studies are registered at ClinicalTrials.gov under the identifiers NCT00474695 (http://clinicaltrials. gov/ct2/show/NCT00474695) and NCT01464723 (http://clinicaltrials.gov/ct2/show/NCT01464723).
To evaluate the safety of up to 3 years of pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD).
Two concurrent, prospective, multicentre, double-masked ...studies randomised subjects with all angiographic lesion compositions of NV-AMD to receive intravitreous pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were rerandomised to continue or discontinue therapy for 48 more weeks; sham-treated subjects continued sham, discontinued or received pegaptanib. At 102 weeks, subjects receiving pegaptanib 0.3 mg or 1 mg in years 1 or 2 continued; those receiving pegaptanib 3 mg or who did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg for year 3.
As in years 1 and 2, pegaptanib was well tolerated in year 3. Adverse events were mainly ocular in nature, mild, transient and injection-related. Serious adverse events were rare. No evidence of systemic safety signals attributed to vascular endothelial growth factor inhibition arose in year 3. There were no findings in relation to vital signs or electrocardiogram results suggesting a relationship to pegaptanib treatment.
The 3-year safety profile of pegaptanib sodium was favourable in patients with NV-AMD.
In surveys, clients have expressed preferences for alternatives to traditional HIV counseling and testing. Few data exist to document how offering such alternatives affects acceptance of HIV testing ...and receipt of test results.
This randomized controlled trial compared types of HIV tests and counseling at a needle exchange and 2 bathhouses to determine which types most effectively ensured that clients received test results.
Four alternatives were offered on randomly determined days: (1) traditional test with standard counseling, (2) rapid test with standard counseling, (3) oral fluid test with standard counseling, and (4) traditional test with choice of written pretest materials or standard counseling.
Of 17,010 clients offered testing, 7014 (41%) were eligible; of those eligible, 761 (11%) were tested: 324 at the needle exchange and 437 at the bathhouses. At the needle exchange, more clients accepted testing (odds ratio OR = 2.3; P < 0.001) and received results (OR = 2.6; P < 0.001) on days when the oral fluid test was offered compared with the traditional test. At the bathhouses, more clients accepted oral fluid testing (OR = 1.6; P < 0.001), but more clients overall received results on days when the rapid test was offered (OR = 1.9; P = 0.01).
Oral fluid testing and rapid blood testing at both outreach venues resulted in significantly more people receiving test results compared with traditional HIV testing. Making counseling optional increased testing at the needle exchange but not at the bathhouses.
To determine strategies to overcome barriers to HIV testing among persons at risk.
We developed a survey that elicited testing motivators, barriers, and preferences for new strategies among 460 ...participants at a needle exchange, three sex venues for men who have sex with men, and a sexually transmitted disease clinic.
Barriers to testing included factors influenced by individual concern (fear and discrimination); by programs, policies, and laws (named reporting and inability to afford treatment); and by counseling and testing strategies (dislike of counseling, anxiety waiting for results, and venipuncture). The largest proportions of participants preferred rapid testing strategies, including clinic-based testing (27%) and home self-testing (20%); roughly equal proportions preferred oral fluid testing (18%), urine testing (17%), and standard blood testing (17%). One percent preferred home specimen collection. Participants who had never tested before were significantly more likely to prefer home self-testing compared with other strategies. Blacks were significantly more likely to prefer urine testing.
Strategies for improving acceptance of HIV counseling and testing include information about access to anonymous testing and early treatment. Expanding options for rapid testing, urine testing, and home self-testing; providing alternatives to venipuncture; making pretest counseling optional; and allowing telephone results disclosure may encourage more persons to learn their HIV status.
Glaucoma is a progressive optic neuropathy with characteristic structural changes in the optic nerve head reflected in the visual field. The visual-field sensitivity test is commonly used in a ...clinical setting to evaluate glaucoma. Standard automated perimetry (SAP) is a common computerized visual-field test whose output is amenable to machine learning. We compared the performance of a number of machine learning algorithms with STATPAC indexes mean deviation, pattern standard deviation, and corrected pattern standard deviation. The machine learning algorithms studied included multilayer perceptron (MLP), support vector machine (SVM), and linear (LDA) and quadratic discriminant analysis (QDA), Parzen window, mixture of Gaussian (MOG), and mixture of generalized Gaussian (MGG). MLP and SVM are classifiers that work directly on the decision boundary and fall under the discriminative paradigm. Generative classifiers, which first model the data probability density and then perform classification via Bayes' rule, usually give deeper insight into the structure of the data space. We have applied MOG, MGG, LDA, QDA, and Parzen window to the classification of glaucoma from SAP. Performance of the various classifiers was compared by the areas under their receiver operating characteristic curves and by sensitivities (true-positive rates) at chosen specificities (true-negative rates). The machine-learning-type classifiers showed improved performance over the best indexes from STATPAC. Forward-selection and backward-elimination methodology further improved the classification rate and also has the potential to reduce testing time by diminishing the number of visual-field location measurements.
To determine whether there is an association between hepatic lipase (LIPC) and age-related macular degeneration (AMD) in two independent Caucasian cohorts.
A discovery cohort of 1626 patients with ...advanced AMD and 859 normal controls and a replication cohort of 2159 cases and 1150 controls were genotyped for two single-nucleotide polymorphisms (SNPs) in the promoter region of LIPC. The associations between the SNPs and AMD were examined by χ(2) tests.
In the discovery cohort, rs493258 and rs10468017 were both associated with advanced AMD (P=9.63E-3 and P=0.048, respectively). The association was corroborated in the replication cohort (P=4.48E-03 for rs493258 and P=0.015 for rs10468017). Combined analysis resulted in even more significant associations (P=1.21E-04 for rs493258 and P=1.67E-03 for rs10468017).
The LIPC promoter variants rs493258 and rs10468017 were associated with advanced AMD in two independent Caucasian populations, confirming that LIPC polymorphisms may be a genetic risk factor for AMD in the Caucasian population.
To compare the non-decanted (standard) 4 mg versus the decanted 20 mg intravitreal triamcinolone acetonide (IVTA) injections and to assess their effect on intraocular pressure (IOP).
We ...retrospectively reviewed the records of 92 consecutive eyes, which received an intravitreal injection of either dose of triamcinolone acetonide, at a single retina centre. The change in IOP (elevation of at least 5 mm Hg from baseline or above 21 mm Hg) was analysed with a multivariate logistic analysis. The mean follow-up period in both groups was 27 weeks. A subgroup analysis comparing vitrectomised to non-vitrectomised eyes in both groups was also performed.
Of the 92 eyes, 46% (23 of 51) in the 4 mg group versus 30% (12 of 41) in the 20 mg group had an IOP >21 mm of Hg (p = 0.14) after a mean follow-up period of 27 weeks. The vitrectomised eyes (3 of 24) in the 20 mg group had a significantly lower rate of IVTA induced IOP elevation than the non-vitrectomised eyes (9 of 17) (p = 0.013). The IOP elevation occurred significantly earlier in the 4 mg group (vitrectomised eyes 27 (SD 43) days and non-vitrectomised eyes 61 (52) days) than in the 20 mg group (vitrectomised eyes 104 (56) days and non-vitrectomised eyes 119 (82) days), independent of the vitreous status (vitrectomised p = 0.05 and non-vitrectomised p = 0.04). The mean value of initial high IOP in the non-vitrectomised eyes was higher in the 4 mg group than in the corresponding 20 mg group (p = 0.048).
Decanted 20 mg IVTA may not pose a significantly greater risk of IOP elevation than the 4 mg non-decanted IVTA.
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