Association of variants in the ATXN2 (rs7137828), FOXC1 (rs2745572) and TXNRD2 (rs35934224) genes as risk factors for primary open-angle glaucoma development in a Brazilian cohort.

BACKGROUND: Primary open-angle glaucoma (POAG), the world's main cause of irreversible blindness, is an asymptomatic and neurodegenerative disease of multifactorial etiology with ethnic and geographic disparities. Multiethnic genome-wide association studies (GWAS) identified single nucleotide variants (SNVs) in ATXN2, FOXC1, and TXNRD2 loci as risk factors for POAG pathophysiology and/or endophenotypes. The aim of this case-control study was to investigate the association of the variants rs7137828 (ATXN2), rs2745572 (FOXC1), and rs35934224 (TXNRD2), as risk factors for POAG development, additionally to rs7137828 association with glaucoma clinical parameters in a Brazilian cohort from the Southeast and South regions. METHODS: This investigation comprised 506 cases and 501 controls. Variants rs2745572 and rs35934224 were genotyped through TaqMan® assays and validated by Sanger sequencing. Variant rs7137828 was genotyped exclusively by Sanger sequencing. RESULTS: The primary research outcome revealed that the variant rs7137828 (ATXN2) was associated with an increased risk for the development of POAG in the presence of the TT genotype compared to the CC genotype (p = 0.006; Odds Ratio [OR] = 1.717; Confidence Interval [CI] 95% = 1.169-2.535). There was no significant association of rs2745572 and rs35934224 genotypes with POAG. The CT genotype of the rs7137828 was associated with the vertical cup-to-disk ratio (VCDR) (p = .023) but not with the age at diagnosis or the mean deviation. CONCLUSION: Our data indicate the rs7137828 associated with increased risk for the development of POAG and VCDR in a Brazilian cohort. If validated in additional populations, these findings may enable the development of relevant strategies for early diagnosis of glaucoma in the future.

Automated algorithms combining structure and function outperform general ophthalmologists in diagnosing glaucoma.

PURPOSE: To test the ability of machine learning classifiers (MLCs) using optical coherence tomography (OCT) and standard automated perimetry (SAP) parameters to discriminate between healthy and glaucomatous individuals, and to compare it to the diagnostic ability of the combined structure-function index (CSFI), general ophthalmologists and glaucoma specialists. DESIGN: Cross-sectional prospective study. METHODS: Fifty eight eyes of 58 patients with early to moderate glaucoma (median value of the mean deviation = -3.44 dB; interquartile range, -6.0 to -2.4 dB) and 66 eyes of 66 healthy individuals underwent OCT and SAP tests. The diagnostic accuracy (area under the ROC curve-AUC) of 10 MLCs was compared to those obtained with the CSFI, 3 general ophthalmologists and 3 glaucoma specialists exposed to the same OCT and SAP data. RESULTS: The AUCs obtained with MLCs ranged from 0.805 (Classification Tree) to 0.931 (Radial Basis Function Network, RBF). The sensitivity at 90% specificity ranged from 51.6% (Classification Tree) to 82.8% (Bagging, Multilayer Perceptron and Support Vector Machine Gaussian). The CSFI had a sensitivity of 79.3% at 90% specificity, and the highest AUC (0.948). General ophthalmologists and glaucoma specialists' grading had sensitivities of 66.2% and 83.8% at 90% specificity, and AUCs of 0.879 and 0.921, respectively. RBF (the best MLC), the CSFI, and glaucoma specialists showed significantly higher AUCs than that obtained by general ophthalmologists (P<0.05). However, there were no significant differences between the AUCs obtained by RBF, the CSFI, and glaucoma specialists (P>0.25). CONCLUSION: Our findings suggest that both MLCs and the CSFI can be helpful in clinical practice and effectively improve glaucoma diagnosis in the primary eye care setting, when there is no glaucoma specialist available.

Occurrence of MYOC and CYP1B1 variants in juvenile open angle glaucoma Brazilian patients.

BACKGROUND: The purpose of this study was to screen juvenile open angle glaucoma (JOAG) patients from Brazil for variants within the MYOC and CYP1B1 genes. MATERIAL AND METHODS: In this study, we evaluated the coding regions of MYOC and CYP1B1 genes in 100 non-related patients with JOAG and 200 controls through Sanger sequencing. We also tested the most frequent single nucleotide variants of CYP1B1 for association with JOAG. RESULTS: Sixteen different sequence variants in the MYOC gene were observed in JOAG patients: eight variants were described as neutral and eight were identified in 34 out of 100 patients with JOAG and no controls, thus being considered damaging. In the CYP1B1 gene, nine neutral variants and two damaging alterations were found among JOAG patients. No association between CYP1B1 variants and JOAG was detected. CONCLUSION: While MYOC damaging alterations were highly prevalent (34%), CYP1B1 damaging variants were less frequent (2%) in this cohort of Brazilian JOAG patients.

Intraocular pressure control after the implantation of a second Ahmed glaucoma valve.

The objective of this study is to evaluate the efficacy and safety of a second Ahmed glaucoma valve (AGV) in eyes with refractory glaucoma that had undergone prior Ahmed device implantation. This multicenter, retrospective study evaluated 58 eyes (58 patients) that underwent a second AGV (model S2-n = 50, model FP7-n = 8) due to uncontrolled IOP under maximal medical therapy. Outcome measures included IOP, visual acuity, number of glaucoma medications, and postoperative complications. Success was defined as IOP <21 mmHg (criterion 1) or 30 % reduction of IOP (criterion 2) with or without hypotensive medications. Persistent hypotony (IOP <5 mmHg after 3 months of follow-up), loss of light perception, and reintervention for IOP control were defined as failure. Mean preoperative IOP and mean IOPs at 12 and 30 months were 27.55 ± 1.16 mmHg (n = 58), 14.45 ± 0.83 mmHg (n = 42), and 14.81 ± 0.87 mmHg (n = 16), respectively. The mean numbers of glaucoma medications preoperatively at 12 and 30 months were 3.17 ± 0.16 (n = 58), 1.81 ± 0.2 (n = 42), and 1.83 ± 0.35 (n = 18), respectively. The reductions in mean IOP and number of medications were statistically significant at all time intervals (P < 0.001). According to criterion 1, Kaplan-Meier survival curves disclosed success rates of 62.9 % at 12 months and 56.6 % at 30 months. According to criterion 2, Kaplan-Meier survival curves disclosed success rates of 43.9 % at 12 months and 32.9 % at 30 months. The most frequent early complication was hypertensive phase (10.3 %) and the most frequent late complication was corneal edema (17.2 %). Second AGV implantation may effectively reduce IOP in eyes with uncontrolled glaucoma, and is associated with relatively few complications.

Ahmed Glaucoma Valve Implantation for Refractory Glaucoma in a Tertiary Hospital in Brazil.

Purpose. To evaluate the efficacy of Ahmed Glaucoma Valve (AGV) implantation in patients with refractory glaucoma in a tertiary hospital in Brazil. Methods. Retrospective case series of patients who underwent AGV implantation. Primary outcome was to assess the rate of failure, which was defined as intraocular pressure (IOP) in two consecutive visits greater than 18 or lower than 5 mmHg (criterion 1) or IOP greater than 15 or lower than 5 mmHg (criterion 2). The secondary outcome was to investigate risk factors for failure. Results. 112 eyes from 108 patients underwent AGV implantation between 2000 and 2012. Mean follow-up time was 2.54 (±1.52) years. Kaplan-Meier survival analysis showed cumulative probabilities of success of 80.3%, 68.2%, and 47.3% at 1, 3, and 5 years using 18 mmHg as endpoint. When adopting 15 mmHg as endpoint, cumulative success rates were 80.3%, 60.7%, and 27.3% at 1, 3, and 5 years, respectively. Multivariate analysis with generalized estimating equations revealed that African American ancestry and early hypertensive phase were risk factors for failure (P = 0.001 and P = 0.002, resp.). Conclusion. A success rate of approximately 50% was obtained 5 years after the implantation of an AGV. African American ancestry and early hypertensive phase were associated with increased risk of failure.

Sensitivity and specificity of frequency-doubling technology, tendency-oriented perimetry, SITA Standard and SITA Fast perimetry in perimetrically inexperienced individuals.

PURPOSE: To evaluate the sensitivity and specificity of the screening modes of frequency-doubling technology (FDT), tendency-oriented perimetry (TOP), SITA Standard (SS) and SITA Fast (SF) in perimetrically inexperienced individuals. METHODS: One eye of 64 glaucoma patients and 53 normal subjects who had never undergone automated perimetry were tested with programs C-20-5 (FDT), G1 (TOP) and 24-2 (SS and SF). The gold standard for glaucoma was the presence of a typical glaucomatous optic disc appearance on stereoscopic examination (judged by a glaucoma expert), and intraocular pressure (IOP) > 21 mmHg. The test order among strategies was randomized for each subject. To define an abnormal visual field, we applied three criteria for SS and SF and two criteria for TOP and FDT, all of which have been previously described in the literature. Sensitivities and specificities among the different criteria were compared using the Cochran test. RESULTS: Frequency-doubling technology showed the shortest mean test duration, followed by TOP, SF and SS (p < 0.05). Sensitivity ranges were 87.5-89.1% for SS, 92.2-93.8% for SF, 87.5-89.1% for TOP, and 82.8-85.9% for FDT (p = 0.34). Specificity ranges were 73.6-83% for FDT, 56.6-62.3% for TOP, 60.4-69.8% for SF and 66.0-71.7% for SS. The specificity obtained with criterion 2 for FDT (based on the presence of two or more abnormal locations regardless of the severity of abnormal points) was higher than those measured with the other strategies (p < 0.01). CONCLUSION: When testing individuals with no perimetric experience, moderate sensitivities and specificities should be expected, regardless of the strategy chosen.

[Full Threshold vs. SITA in glaucomatous patients undergoing automated perimetry for the first time]. / Full threshold vs. Swedish interactive threshold algorithm (SITA) em pacientes glaucomatosos submetidos à perimetria computadorizada pela primeira vez.

PURPOSE: To compare the Full Threshold (FT) and SITA Standard (SS) strategies in glaucomatous patients undergoing automated perimetry for the first time. METHODS: Thirty-one glaucomatous patients who had never undergone perimetry underwent automated perimetry (Humphrey, program 30-2) with both FT and SS on the same day, with an interval of at least 15 minutes. The order of the examination was randomized, and only one eye per patient was analyzed. Three analyses were performed: a) all the examinations, regardless of the order of application; b) only the first examinations; c) only the second examinations. In order to calculate the sensitivity of both strategies, the following criteria were used to define abnormality: glaucoma hemifield test (GHT) outside normal limits, pattern standard deviation (PSD) <5%, or a cluster of 3 adjacent points with p<5% at the pattern deviation probability plot. RESULTS: When the results of all examinations were analyzed regardless of the order in which they were performed, the number of depressed points with p<0.5% in the pattern deviation probability map was significantly greater with SS (p=0.037), and the sensitivities were 87.1% for SS and 77.4% for FT (p=0.506). When only the first examinations were compared, there were no statistically significant differences regarding the number of depressed points, but the sensitivity of SS (100%) was significantly greater than that obtained with FT (70.6%) (p=0.048). When only the second examinations were compared, there were no statistically significant differences regarding the number of depressed points, and the sensitivities of SS (76.5%) and FT (85.7%) (p=0.664). CONCLUSION: SS may have a higher sensitivity than FT in glaucomatous patients undergoing automated perimetry for the first time. However, this difference tends to disappear in subsequent examinations.

Full threshold vs. Swedish interactive threshold algorithm (SITA) em pacientes glaucomatosos submetidos à perimetria computadorizada pela primeira vez / Full threshold vs. SITA in glaucomatous patients undergoing automated perimetry for the first time

OBJETIVO: Comparar as estratégias Full Threshold (FT) e SITA Standard (SS) em pacientes glaucomatosos submetidos à perimetria computadorizada pela primeira vez. MÉTODOS: Trinta e um pacientes glaucomatosos sem experiência perimétrica prévia foram submetidos à perimetria computadorizada (Humphrey, programa 30-2) com as estratégias FT e SS num mesmo dia, com um intervalo de tempo de pelo menos 15 minutos. A ordem dos exames foi randomizada, e somente um olho por paciente foi analisado. Foram realizadas três análises comparativas: a) todos os exames, independentemente da ordem de realização; b) somente os primeiros exames; c) somente os segundos exames. Para calcular a sensibilidade das estratégias, adotaram-se os seguintes critérios para definir anormalidade: glaucoma hemifield test (GHT) fora dos limites normais, pattern standard deviation (PSD) <5 por cento, ou agrupamento de 3 pontos adjacentes com p<5 por cento no gráfico de probabilidades pattern deviation. RESULTADOS: Quando todos os exames foram analisados independentemente da ordem de realização, o número de pontos suspeitos com p<0,5 por cento no gráfico de probabilidades pattern deviation foi significativamente maior com SS (p=0,037), e as sensibilidades foram 87,1 por cento para SS e 77,4 por cento para FT (p=0,506). Quando somente os primeiros exames foram comparados, não houve diferença em relação ao número de pontos suspeitos, mas a sensibilidade de SS (100 por cento) foi significantemente maior que aquela obtida com FT (70,6 por cento) (p=0,048). Quando somente os segundos exames foram comparados, não houve diferenças estatisticamente significantes em relação ao número de pontos suspeitos e às sensibilidades de SS (76,5 por cento) e FT (85,7 por cento) (p=0,664). CONCLUSÃO: SS pode apresentar maior sensibilidade que FT em pacientes glaucomatosos submetidos à perimetria computadorizada pela primeira vez. Entretanto, esta diferença tende a desaparecer em exames subseqüentes.

Full-threshold versus Swedish Interactive Threshold Algorithm (SITA) in normal individuals undergoing automated perimetry for the first time.

PURPOSE: To compare the full-threshold (FT) and Swedish Interactive Threshold Algorithm standard (SS) strategies in normal individuals undergoing automated perimetry for the first time. DESIGN: Randomized, comparative, observational case series. PARTICIPANTS: Eighty perimetrically naive normal individuals. METHODS: All individuals underwent computerized visual field examinations (30-2, Humphrey 750, Humphrey-Zeiss, Dublin, CA) with both FT and SS strategies. One eye of each individual was tested. Test order between strategies was randomized. MAIN OUTCOME MEASURES: The following variables were compared: test time, foveal threshold, fixation losses, false-positive and false-negative errors, mean deviation, pattern standard deviation, glaucoma hemifield test, and number of depressed points deviating at P < 5%, P < 2%, P < 1%, and P < 0.5% on the total and pattern deviation probability maps. Initially, we compared the results of all FT and SS tests, regardless of the order in which they were applied. Next, patients undergoing SS as the first examination were compared with those undergoing FT as the first test. Finally, the SS and FT results obtained in the second test were compared. Anderson's criteria were applied to define abnormal examinations, allowing for the calculation of the specificity of the SS and FT strategies. RESULTS: When the results of all FT and SS tests were analyzed, the number of significantly depressed points deviating at P < 5%, P < 2%, and P < 1% on the pattern deviation probability maps was higher with the SS strategy (P < 0.05); the specificity was 50% for SS and 72.5% for FT (P < 0.01). When only first examinations were compared, the number of significantly depressed points deviating at P < 5%, P < 2%, and P < 1% on both the total and pattern deviation probability maps was higher with the SS strategy (P < 0.05); the specificity was 38.1% and 63.2% for the SS and FT strategies, respectively (P = 0.04). When only the second examinations were compared, there were no significant differences either between the number of depressed points or between the specificities of both strategies (73.7% for SS and 71.4% for FT) (P = 0.98). CONCLUSIONS: Normal individuals with no perimetric experience may present more significantly depressed points on the pattern deviation probability map when the SS strategy is used, reducing the test specificity in comparison with FT. These findings are probably due to a lower interindividual variability observed with SS. However, these differences disappeared in a second examination, suggesting that both strategies perform similarly in perimetrically experienced individuals.

Efeitos da constrição pulilar na perimetria de frequência dupla em olhos normais / Effects of pupillary constriction on frequency doubling perimetry in normal eyes

Objetivo: Estudar os efeitos da redução do diâmetro pupilar nos resultados da perimetria de freqüência dupla em um grupo de voluntários normais. Métodos: Dezoito voluntários saudáveis participaram do estudo. Realizou-se perimetria de freqüência dupla no olho direito de cada participante (estratégia " Full Threshold" C-20). Para a segunda sessão de perimetria, instilou-se uma gota de pilocarpina 2 por cento no olho direito dos voluntários e refez-se o exame após 60 minutos. Resultados: Sessenta minutos após adição de pilocarpina 2 por cento houve redução significante do diâmetro pupilar de 4,22 ñ 0,17 mm para 1,55 ñ 0,51 mm (p<0,05). Houve redução significativa da sensibilidade retiniana média após constrição pupilar de 5,67 ñ 2,49 dB nos 5 graus centrais, 4,49 ñ2,73 dB entre 2,5 graus e 10 grause 5,10 ñ 3,55 dB entre 10 graus e 20 graus (p<0,01). Observou-se redução de 4,06ñ2,67 dB no "mean deviation" e aumento de 0,64 ñ 0,94 dB no "pattern standard deviation" (p< 0,01). Não se observaram diferenças em relação às respostas falso-positivas, falso-negativas, perdas de fixação e duração média do exame (p>0,05). Conclusão: A alteração do diâmetro pupilar está associada a redução significativa dos limiares de sensibilidade dentro dos 20 graus centrais do campo testado pela perimetria de freqüência dupla. Estes resultados sugerem que seja importante manter o diâmetro pupilar constante em exames seriados.

Prevalence of refractive errors and ocular disorders in preschool and schoolchildren of Ibiporä-PR, Brazil (1989 to 1996)

Purpose: To establish the prevalence of refractive errors and ocular disorders in preschool and schoolchildren of Ibiporä, Brazil. Methods: A survey of 6 to 12-year-old children from public and private elementary schools was carried out in Ibiporä between 1989 and 1996. Visual acuity measurements were performed by trained teachers using Snellen's chart. Children with visual acuity

Perimetria computadorizada em pacientes glaucomatosos afácicos / Automated perimetry in aphakic glaucomatous patients

Objetivo: comparar os exames de perimetria computadorizada em pacientes glaucomatosos afácicos usando lentes corretivas convencionais (LCC) e lentes de contato gelatinosas (LC). Métodos: foram selecionados 17 pacientes que já haviam realizado pelo menos dois exames anteriormente, sendo aleatória a escolha daqueles que iniciavam o exame utilizando LCC ou LC. A seleçäo da LC era baseada em critérios específicos e o aparelho utilizado foi o Humphrey Field Analizer 630. Foram analisados dados referentes a idade, sexo, cor, equivalente esférico, sensibilidade foveal, tempo para execuçäo do exame, MD, CPSD, SF e acuidade visual. Para a análise estatística foi utilizado o teste t de Student pareado considerando significativos valores de p menores que 0,05. Resultados: foram excluídos quatro pacientes que apresentaram exames com baixa confiabilidade