Influence of upper blepharoplasty on intraocular lens calculation.

PURPOSE: To determine the effect of upper blepharoplasty on corneal topography and intraocular lens power calculation using Galilei and IOLMaster. METHODS: Thirty patients submitted to upper blepharoplasty from May 2014 to March 2017 at the Hospital Oftalmológico de Sorocaba (São Paulo, Brazil) were included in this observational case series. All patients underwent imaging sessions with Galilei and IOLMaster preoperatively (baseline) and at 1 and 6 months postoperatively. Primary outcome measures using both devices included flattest, average, and steepest corneal curvature, corneal astigmatism, and blepharoplasty-induced corneal astigmatism. Determination of axial length and lens power calculation were performed using only IOLMaster (Holladay formula). Paired t-test and vectorial analysis were used for statistical analysis. RESULTS: Sixty eyes from 30 patients were prospectively included. Vectorial analysis showed that 6 months after surgery, blepharoplasty induced on average 0.39 D and 0.31 D of corneal astigmatism, as measured with Galilei and IOLMaster, respectively. IOLMaster measurements showed that average corneal curvature (44.56 vs 44.64 D, p=0.01), steepest corneal curvature (45.17 vs 45.31, p=0.01) and corneal astigmatism (1.22 vs 1.34, p=0.03) were higher 6 months after surgery. IOLMaster measurements also showed that intraocular lens power was significantly smaller 6 months after surgery (22.07 vs 21.93, p=0.004). All other parameters showed no change for comparisons between baseline and 6 months (p>0.05 for all comparisons). CONCLUSION: Upper eyelid blepharoplasty influenced intraocular lens calculation using the IOLMaster. However, the influence was not clinically significant. No topographic changes were found using Galilei.

Influence of upper blepharoplasty on intraocular lens calculation / A influência da blefaroplastia superior no cálculo da lente intraocular

ABSTRACT Purpose: To determine the effect of upper blepharoplasty on corneal topography and intraocular lens power calculation using Galilei and IOLMaster. Methods: Thirty patients submitted to upper blepharoplasty from May 2014 to March 2017 at the Hospital Oftalmológico de Sorocaba (São Paulo, Brazil) were included in this observational case series. All patients underwent imaging sessions with Galilei and IOLMaster preoperatively (baseline) and at 1 and 6 months postoperatively. Primary outcome measures using both devices included flattest, average, and steepest corneal curvature, corneal astigmatism, and blepharoplasty-induced corneal astigmatism. Determination of axial length and lens power calculation were performed using only IOLMaster (Holladay formula). Paired t-test and vectorial analysis were used for statistical analysis. Results: Sixty eyes from 30 patients were prospectively included. Vectorial analysis showed that 6 months after surgery, blepharoplasty induced on average 0.39 D and 0.31 D of corneal astigmatism, as measured with Galilei and IOLMaster, respectively. IOLMaster measurements showed that average corneal curvature (44.56 vs 44.64 D, p=0.01), steepest corneal curvature (45.17 vs 45.31, p=0.01) and corneal astigmatism (1.22 vs 1.34, p=0.03) were higher 6 months after surgery. IOLMaster measurements also showed that intraocular lens power was significantly smaller 6 months after surgery (22.07 vs 21.93, p=0.004). All other parameters showed no change for comparisons between baseline and 6 months (p>0.05 for all comparisons). Conclusion: Upper eyelid blepharoplasty influenced intraocular lens calculation using the IOLMaster. However, the influence was not clinically significant. No topographic changes were found using Galilei.

RESUMO Objetivo: Determinar o efeito da blefaroplastia superior na topografia corneana e no cálculo do poder das lentes intraoculares usando Galilei e IOLMaster. Métodos: Trinta pacientes submetidos a blefaroplastia superior de maio de 2014 a março de 2017 no Hospital Oftalmológico de Sorocaba, São Paulo, Brasil foram incluídos neste estudo de série de casos observacional. Todos os pacientes foram submetidos a sessões de imagem com Galilei e IOLMaster antes da cirurgia (exame de base) e no 1º e 6º mês pós-operatório. Os resultados primários utilizando os dois aparelhos incluíram ceratometria, astigmatismo corenano e astigmatismo corneano induzido pela blefaroplastia. O comprimento axial e o cálculo do poder da lente intraocular foram realizados unicamente com o IOLMaster (fórmula de Holladay). Teste-t pareado e análise vetorial foram usados na análise estatística. Resultados: Sessenta olhos de 30 pacientes foram incluídos prospectivamente. A análise vec­torial mostrou que após 6 meses da cirurgia, a blefaroplastia superior induziu na média 0,39 D de astigmatismo corneano medido com o Galilei e 0,31 D com IOLMaster. As medidas com o IOLMaster mostraram que a ceratometria média (44,56 vs 44,64 D, p=0,01), ceratometria máxima (45,17 vs 45,31, p=0,01) e o astigmatismo corneano (1,22 vs 1,34, p=0,03) foram maiores após 6 meses da blefaroplastia. As medidas com IOLMaster mostraram que o poder da lente intraocular foi significativamente menor 6 meses após a blefaroplastia (22,07 vs 21,93, p=0,004). Todos os outros parâmetros não mostraram mudanças entre o pré-operatório e o 6º mês da cirurgia (p>0,05 para todas as comparações). Conclusões: A blefaroplastia superior influenciou o cálculo da lente intrao­cular utilizando o IOLMaster. Contudo, a influência não foi cli­­nicamente significativa. Não foram encontradas mudanças topográficas com o Galilei.

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.

Use of statistical analyses in the ophthalmic literature.

PURPOSE: To identify the most commonly used statistical analyses in the ophthalmic literature and to determine the likely gain in comprehension of the literature that readers could expect if they were to add knowledge of more advanced techniques sequentially to their statistical repertoire. DESIGN: Cross-sectional study. METHODS: All articles published from January 2012 through December 2012 in Ophthalmology, the American Journal of Ophthalmology, and Archives of Ophthalmology were reviewed. A total of 780 peer-reviewed articles were included. Two reviewers examined each article and assigned categories to each one depending on the type of statistical analyses used. Discrepancies between reviewers were resolved by consensus. MAIN OUTCOME MEASURES: Total number and percentage of articles containing each category of statistical analysis were obtained. Additionally, we estimated the accumulated number and percentage of articles that a reader would be expected to be able to interpret depending on their statistical repertoire. RESULTS: Readers with little or no statistical knowledge would be expected to be able to interpret the statistical methods presented in only 20.8% of articles. To understand more than half (51.4%) of the articles published, readers would be expected to be familiar with at least 15 different statistical methods. Knowledge of 21 categories of statistical methods was necessary to comprehend 70.9% of articles, whereas knowledge of more than 29 categories was necessary to comprehend more than 90% of articles. Articles related to retina and glaucoma subspecialties showed a tendency for using more complex analysis when compared with articles from the cornea subspecialty. CONCLUSIONS: Readers of clinical journals in ophthalmology need to have substantial knowledge of statistical methodology to understand the results of studies published in the literature. The frequency of the use of complex statistical analyses also indicates that those involved in the editorial peer-review process must have sound statistical knowledge to appraise critically the articles submitted for publication. The results of this study could provide guidance to direct the statistical learning of clinical ophthalmologists, researchers, and educators involved in the design of courses for residents and medical students.

Evaluation of progressive neuroretinal rim loss as a surrogate end point for development of visual field loss in glaucoma.

PURPOSE: To evaluate the validity of using progressive loss of neuroretinal rim area as a surrogate end point for the development of visual field loss in glaucoma. DESIGN: Prospective, observational cohort study. PARTICIPANTS: The study group included 492 eyes of 328 patients classified with suspected glaucoma at the baseline visit. These eyes had an average of 7.4±2.8 confocal scanning laser ophthalmoscopy (CSLO) images during a mean follow-up time of 6.6±1.6 years. METHODS: Rim area measurements were acquired with CSLO during follow-up. The visual field end point was considered the development of 3 consecutive abnormal visual fields on standard automated perimetry. Strong predictive ability and large proportion of treatment effect (PTE) explained are requisites for a suitable surrogate end point. A joint longitudinal survival model was used to evaluate the ability of rates of rim area loss in predicting visual field development, adjusting for confounding variables (baseline age, race, and corneal thickness and follow-up measurements of intraocular pressure [IOP] and pattern standard deviation). The PTE was calculated by comparing the effect of IOP on the risk of development of visual field loss when incorporating rim area loss in the same model with the effect of IOP in the model excluding rim area measurements. MAIN OUTCOME MEASURES: Predictive strength was measured by survival-adapted R(2) and PTE. RESULTS: Sixty-two of 492 eyes (13%) developed visual field loss during follow-up. The mean rate of rim area change in eyes that developed visual field loss was -0.011 mm(2)/year versus -0.003 mm(2)/year in eyes that did not (P<0.001). In the multivariable model, each 0.01 mm(2)/year faster rate of rim area loss was associated with a 2.94 higher risk of visual field loss (hazard ratio, 2.94; 95% confidence interval, 1.38-6.23; P = 0.005). R(2) values were 62% and 81% for univariable and multivariable models, respectively. The PTE was 65%. CONCLUSIONS: Progressive rim area loss was highly predictive of the development of visual field loss in glaucoma and explained a significant PTE on the clinically relevant outcome. These findings suggest that rim area measurements may be suitable surrogate end points in glaucoma clinical trials.

Predicting progression of glaucoma from rates of frequency doubling technology perimetry change.

PURPOSE: To evaluate the ability of longitudinal frequency doubling technology (FDT) to predict the development of glaucomatous visual field loss on standard automated perimetry (SAP) in glaucoma suspects. DESIGN: Prospective, observational cohort study. PARTICIPANTS: The study included 587 eyes of 367 patients with suspected glaucoma at baseline selected from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). These eyes had an average of 6.7 ± 1.9 FDT tests during a mean follow-up time of 73.1 ± 28.0 months. METHODS: Glaucoma suspects had intraocular pressure (IOP) >21 mmHg or an optic disc appearance suspicious of glaucoma. All patients had normal or nonrepeatable abnormal SAP at baseline. Humphrey Matrix FDT (Carl Zeiss Meditec, Inc, Dublin, CA) testing was performed within 6 months of SAP testing. The study end point was the development of 3 consecutive abnormal SAP test results. Joint longitudinal survival models were used to evaluate the ability of rates of FDT pattern standard deviation (PSD) change to predict the development of visual field loss on SAP, adjusting for confounding variables (baseline age, mean IOP, corneal thickness, and follow-up measurements of SAP PSD). MAIN OUTCOME MEASURES: The R(2) index was used to evaluate and compare the predictive abilities of the model containing longitudinal FDT PSD data with the model containing only baseline data. RESULTS: Sixty-three of 587 eyes (11%) developed SAP visual field loss during follow-up. The mean rate of FDT PSD change in eyes that developed SAP visual field loss was 0.07 dB/year versus 0.02 dB/year in those that did not (P < 0.001). Baseline FDT PSD and slopes of FDT PSD change were significantly predictive of progression, with hazard ratios of 1.11 per 0.1 dB higher (95% confidence interval [CI], 1.04-1.18; P = 0.002) and 4.40 per 0.1 dB/year faster (95% CI, 1.08-17.96; P = 0.04), respectively. The longitudinal model performed significantly better than the baseline model with an R(2) of 82% (95% CI, 74-89) versus 11% (95% CI, 2-24), respectively. CONCLUSIONS: Rates of FDT PSD change were highly predictive of the development of SAP visual field loss in glaucoma suspects. This finding suggests that longitudinal FDT evaluation may be useful for risk stratification of patients with suspected glaucoma.

Prevalence and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus in ocular infections / Prevalência e suscetibilidade antibiótica de Staphylococcus aureus resistente à meticilina em infecções oculares

PURPOSE: To study the prevalence of methicillin-resistant Staphylococcus aureus among S. aureus ocular infections in a tertiary health center in Brazil and compare antibiotic susceptibility patterns between MRSA and methicillin-susceptible S. aureus isolates. METHODS: Electronic records from the ocular microbiology laboratory of the Universidade Federal de São Paulo were retrospectively reviewed. During a 10-year period (between January 2000 and December 2009) all conjunctivitis, keratitis, and endophthalmitis cases with a positive culture for S. aureus were identified. Antibiotic susceptibility was determined using the Kirby-Bauer disk diffusion method. RESULTS: Five hundred sixty-six S. aureus isolates were identified; of those, 56 (9.9%) were resistant to methicillin. Throughout the 10-year period, Staphylococcus aureus showed a significant increasing trend from 7.55% to 16.18% among overall S. aurues infections (p=0.001) and from 3.7% to 13.16% in conjunctivitis (p=0.001). Conversely, we did not observe the same trend among those with keratitis (p=0.38). Staphylococcus aureus isolates showed higher resistance rates to tobramycin, gentamicin, ciprofloxacin, gatifloxacin, and moxifloxacin when compared with S. aureus isolates (p< 0.001). All cases were susceptible to vancomycin. CONCLUSION: We observed an increasing trend in the overall prevalence of Staphylococcus aureus ocular infections and statistically significant higher resistance rates to commonly used antibiotics compared to Staphylococcus aureus. Our data supports the need for constant bacterial surveillance and should be taken into consideration before initiating empiric treatment of ocular infections.

OBJETIVO: Estudar a prevalência do Staphylococcus aureus resistente à meticilina nas infecções oculares causadas por S. aureus em um centro de saúde terciário no Brasil e comparar o perfil de suscetibilidade antimicrobiana entre as cepas de Staphylococcus aureus resistente à meticilina e S. aureus susceptível à meticilina MÉTODOS: Foi realizada uma análise retrospectiva dos arquivos do laboratório de microbiologia ocular da Universidade Federal de São Paulo e selecionados todos os casos de conjuntivite, ceratite e endoftalmite com cultivo positivo para S. aureus, durante um período de 10 anos (entre janeiro de 2000 e dezembro de 2009). Foi avaliada a prevalência de Staphylococcus aureus resistente à meticilina e comparado o perfil de susceptibilidade antimicrobiano dos Staphylococcus aureus resistente à meticilina e S. aureus susceptível à meticilina. RESULTADOS: Quinhentos e sessenta e seis isolados de S. aureus foram identificados. Desses, 56 (9,9%) apresentaram resistência à meticilina. Durante o período de 10 anos estudado, Staphylococcus aureus resistente à meticilina mostrou uma tendência significante de aumento de 7,6% para 16,2% entre as infecções oculares causadas por S. aureus em geral (p=0,001) e de 3,7% para 13,2% nas conjuntivites (p=0,001). A mesma tendência não foi observada entre as amostras de ceratite (p=0,38). Os isolados de Staphylococcus aureus resistente à meticilina mostraram maiores taxas de resistência à tobramicina, gentamicina, ciprofloxacino, gatifloxacino e moxifloxacino em comparação com os isolados de S. aureus susceptível à meticilina (p<0,001). Todos os casos foram susceptíveis à vancomicina. CONCLUSÃO:Foi observada uma tendência de aumento na prevalência do Staphylococcus aureus resistente à meticilina nas infecções oculares causadas por S. aureus, bem como taxas de resistência significantemente maiores aos antibióticos comumente utilizados na prática oftalmológica. Nossos dados alertam para a necessidade de constante vigilância de resistência bacteriana a antimicrobianos e devem ser considerados na eleição do tratamento empírico das infecções oculares.

Likelihood ratios for glaucoma diagnosis using spectral-domain optical coherence tomography.

PURPOSE: To present a methodology for calculating likelihood ratios for glaucoma diagnosis for continuous retinal nerve fiber layer (RNFL) thickness measurements from spectral-domain optical coherence tomography (spectral-domain OCT). DESIGN: Observational cohort study. METHODS: A total of 262 eyes of 187 patients with glaucoma and 190 eyes of 100 control subjects were included in the study. Subjects were recruited from the Diagnostic Innovations Glaucoma Study. Eyes with preperimetric and perimetric glaucomatous damage were included in the glaucoma group. The control group was composed of healthy eyes with normal visual fields from subjects recruited from the general population. All eyes underwent RNFL imaging with Spectralis spectral-domain OCT. Likelihood ratios for glaucoma diagnosis were estimated for specific global RNFL thickness measurements using a methodology based on estimating the tangents to the receiver operating characteristic (ROC) curve. RESULTS: Likelihood ratios could be determined for continuous values of average RNFL thickness. Average RNFL thickness values lower than 86 µm were associated with positive likelihood ratios (ie, likelihood ratios greater than 1), whereas RNFL thickness values higher than 86 µm were associated with negative likelihood ratios (ie, likelihood ratios smaller than 1). A modified Fagan nomogram was provided to assist calculation of posttest probability of disease from the calculated likelihood ratios and pretest probability of disease. CONCLUSION: The methodology allowed calculation of likelihood ratios for specific RNFL thickness values. By avoiding arbitrary categorization of test results, it potentially allows for an improved integration of test results into diagnostic clinical decision making.

Corneal hysteresis as a risk factor for glaucoma progression: a prospective longitudinal study.

PURPOSE: To evaluate the role of corneal hysteresis (CH) as a risk factor for the rate of visual field progression in a cohort of patients with glaucoma followed prospectively over time. DESIGN: Prospective observational cohort study. PARTICIPANTS: The study group included 114 eyes of 68 patients with glaucoma followed for an average of 4.0 ± 1.1 years. Visual fields were obtained with standard automated perimetry. Included eyes had a median number of 7 (range, 5-12) tests during follow-up. METHODS: The CH measurements were acquired at baseline using the Ocular Response Analyzer (Reichert Instruments, Depew, NY). Evaluation of rates of visual field change during follow-up was performed using the visual field index (VFI). Linear mixed models were used to investigate the relationship between rates of visual field loss and baseline CH, baseline intraocular pressure (IOP), and central corneal thickness (CCT), while adjusting for potentially confounding factors. An interaction term between IOP and CH was included in the model to investigate whether the effect of IOP on rates of progression depended on the level of CH. MAIN OUTCOME MEASURES: Effects of CH, IOP, and CCT on rates of VFI loss over time. RESULTS: The CH had a significant effect on rates of visual field progression over time. In the univariable model including only CH as a predictive factor along with time and their interaction, each 1 mmHg lower CH was associated with a 0.25%/year faster rate of VFI decline over time (P<0.001). The multivariable model showed that the effect of IOP on rates of progression depended on CH. Eyes with high IOP and low CH were at increased risk for having fast rates of disease progression. The CH explained a larger proportion of the variation in slopes of VFI change than CCT (17.4% vs. 5.2%, respectively). CONCLUSIONS: The CH measurements were significantly associated with risk of glaucoma progression. Eyes with lower CH had faster rates of visual field loss than those with higher CH. The prospective longitudinal design of this study supports the role of CH as an important factor to be considered in the assessment of the risk of progression in patients with glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Predicting progression in glaucoma suspects with longitudinal estimates of retinal ganglion cell counts.

PURPOSE: We evaluated the ability of baseline and longitudinal estimates of retinal ganglion cell (RGC) counts in predicting progression in eyes suspected of having glaucoma. METHODS: The study included 288 glaucoma suspect eyes of 288 patients followed for an average of 3.8 ± 1.0 years. Participants had normal standard automated perimetry (SAP) at baseline. Retinal nerve fiber layer thickness assessment was performed with optical coherence tomography (OCT). Progression was defined as development of repeatable abnormal SAP or glaucomatous progressive optic disc changes. Estimates of RGC counts were obtained by combining data from SAP and OCT according to a previously described method. Joint longitudinal survival models were used to evaluate the ability of baseline and rates of change in estimated RGC counts for predicting progression over time, adjusting for confounding variables. RESULTS: A total of 48 eyes (17%) showed progression during follow-up. The mean rate of change in estimated RGC counts was -18,987 cells/y in progressors versus -8,808 cells/y for nonprogressors (P < 0.001). Baseline RGC counts and slopes of RGC loss were significantly predictive of progression, with HRs of 1.56 per 100,000 cells lower (95% confidence interval [CI], 1.18-2.08; P = 0.002) and 2.68 per 10,000 cells/y faster loss (95% CI, 1.22-5.90; P = 0.014), respectively. The longitudinal model including estimates of RGC counts performed significantly better than models including only structural or functional indexes separately. CONCLUSIONS: Baseline and longitudinal estimates of RGC counts may be helpful in predicting progression and performed significantly better than conventional approaches for risk stratification of glaucoma suspects.

Association between rates of binocular visual field loss and vision-related quality of life in patients with glaucoma.

IMPORTANCE: It is reasonable to hypothesize that for 2 patients with similar degrees of integrated binocular visual field (BVF) loss, the patient with a history of faster disease progression will report worse vision-related quality of life (VRQOL) than the patient with slowly progressing damage. However, to our knowledge, this hypothesis has not been investigated in the literature. OBJECTIVE: To evaluate the association between binocular rates of visual field change and VRQOL in patients with glaucoma. DESIGN Observational cohort study. SETTING: Patients were recruited from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. PARTICIPANTS: The study included 796 eyes of 398 patients with diagnosed or suspected glaucoma followed up from October 1, 1998, until January 31, 2012, for a mean (SD) of 7.3 (2.0) years. MAIN OUTCOME MEASURES: The VRQOL was evaluated using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) at the last follow-up visit. The NEI VFQ-25 was completed for all patients during the period extending from December 1, 2009, through January 31, 2012. Integrated BVFs were calculated from the monocular fields of each patient. Linear regression of mean deviation values was used to evaluate rates of BVF change during the follow-up period. Logistic regression models were used to investigate the association between abnormal VRQOL and rates of BVF change, while adjusting for potentially confounding socioeconomic and demographic variables. RESULTS: Thirty-two patients (8.0%) had abnormal VRQOL as determined by the results of the NEI VFQ-25. Patients with abnormal VRQOL had significantly faster rates of BVF change than those with normal VRQOL (-0.18 vs -0.06 dB/y; P < .001). Rates of BVF change were significantly associated with abnormality in VRQOL (odds ratio = 1.31 per 0.1 dB/y faster; P = .04), after adjustment for confounding variables. CONCLUSIONS AND RELEVANCE: Patients with faster rates of BVF change were at higher risk of reporting abnormal VRQOL. Assessment of rates of BVF change may provide useful information in determining risk of functional impairment in glaucoma.

Comparison of different spectral domain OCT scanning protocols for diagnosing preperimetric glaucoma.

PURPOSE: To compare the ability of spectral-domain optical coherence tomography (SDOCT) retinal nerve fiber layer (RNFL), optic nerve head (ONH), and macular measurements to detect preperimetric glaucomatous damage. METHODS: The study included 142 eyes from 91 patients suspected of having the disease based on the appearance of the optic disc. All eyes had normal visual fields before the imaging session. Forty-eight eyes with progressive glaucomatous damage were included in the preperimetric glaucoma group. Ninety-four eyes without any evidence of progressive glaucomatous damage and followed untreated for 12.8 ± 3.6 years were used as controls. Areas under the receiver operating characteristic curves (AUC) were calculated to summarize diagnostic accuracies of the parameters. RESULTS: The three RNFL parameters with the largest AUCs were average RNFL thickness (0.89 ± 0.03), inferior hemisphere average thickness (0.87 ± 0.03), and inferior quadrant average thickness (0.85 ± 0.03). The three ONH parameters with the largest AUCs were vertical cup-to-disc ratio (0.74 ± 0.04), rim area (0.72 ± 0.05), and rim volume (0.72 ± 0.05). The three macular parameters with the largest AUCs were GCC average thickness (0.79 ± 0.04), GCC inferior thickness (0.79 ± 0.05), and GCC superior thickness (0.76 ± 0.05). Average RNFL thickness performed better than vertical cup-to-disc ratio (0.89 vs. 0.74; P = 0.007) and GCC average thickness (0.89 vs. 0.79; P = 0.015). CONCLUSIONS: SDOCT RNFL measurements performed better than ONH and macular measurements for detecting preperimetric glaucomatous damage in a cohort of glaucoma suspects. (ClinicalTrials.gov number, NCT00221897.).

Prevalence and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus in ocular infections.

PURPOSE: To study the prevalence of methicillin-resistant Staphylococcus aureus among S. aureus ocular infections in a tertiary health center in Brazil and compare antibiotic susceptibility patterns between MRSA and methicillin-susceptible S. aureus isolates. METHODS: Electronic records from the ocular microbiology laboratory of the Universidade Federal de São Paulo were retrospectively reviewed. During a 10-year period (between January 2000 and December 2009) all conjunctivitis, keratitis, and endophthalmitis cases with a positive culture for S. aureus were identified. Antibiotic susceptibility was determined using the Kirby-Bauer disk diffusion method. RESULTS: Five hundred sixty-six S. aureus isolates were identified; of those, 56 (9.9%) were resistant to methicillin. Throughout the 10-year period, Staphylococcus aureus showed a significant increasing trend from 7.55% to 16.18% among overall S. aurues infections (p=0.001) and from 3.7% to 13.16% in conjunctivitis (p=0.001). Conversely, we did not observe the same trend among those with keratitis (p=0.38). Staphylococcus aureus isolates showed higher resistance rates to tobramycin, gentamicin, ciprofloxacin, gatifloxacin, and moxifloxacin when compared with S. aureus isolates (p< 0.001). All cases were susceptible to vancomycin. CONCLUSION: We observed an increasing trend in the overall prevalence of Staphylococcus aureus ocular infections and statistically significant higher resistance rates to commonly used antibiotics compared to Staphylococcus aureus. Our data supports the need for constant bacterial surveillance and should be taken into consideration before initiating empiric treatment of ocular infections.

Advances in the Structural Evaluation of Glaucoma with Optical Coherence Tomography.

Optical coherence tomography (OCT) is capable of providing quantitative and objective assessments of the optic disc, macula and retinal nerve fiber layer in glaucoma. The recent advent of spectral domain OCT (SD-OCT) has enhanced the resolution, decreased scan acquisition time, and improved the reproducibility of measurements compared to older versions of this technology. However, although OCT has been successfully used for detection of disease and evaluation of progression, the limited agreement between structural and functional tests indicates the strong need for a combined approach for detecting and monitoring the disease. A recently described approach for estimation of rates of retinal ganglion cell loss from a combination of SD-OCT and functional data is a promising method for diagnosing, staging, detecting progression, and estimating rates of glaucomatous deterioration.

Combining structure and function to evaluate glaucomatous progression: implications for the design of clinical trials.

The selection of a suitable method for assessment of glaucomatous progression and estimation of rates of change is an essential component of the design of clinical trials investigating neuroprotective therapies for the disease. Due to the limitations of currently available tests, approaches combining structural and functional tests are essential in order to provide reliable detection of endpoints. This could also potentially enable shorter clinical trials with relatively smaller sample size requirements. A recent approach for estimating rates of retinal ganglion cell loss using a combination of structural and functional tests has been shown to perform better than isolated parameters from conventional tests for diagnosing, staging and detecting glaucoma progression and may prove useful as an outcome measure in clinical trials of the disease.

Retinal ganglion cell count estimates associated with early development of visual field defects in glaucoma.

PURPOSE: To estimate retinal ganglion cell (RGC) losses associated with the earliest development of visual field defects in glaucoma. DESIGN: Observational cohort study. PARTICIPANTS: The study group included 53 eyes of 53 patients with suspected glaucoma who were followed as part of the Diagnostic Innovations in Glaucoma (DIGS) study. These eyes had normal standard automated perimetry (SAP) visual fields at baseline and developed repeatable (3 consecutive) abnormal test results during a median follow-up of 6.7 years. An age-matched control group of 124 eyes of 124 healthy subjects recruited from the general population was included. METHODS: Estimates of RGC counts were obtained using a previously published model that combines estimates of RGC numbers from SAP sensitivity thresholds and retinal nerve fiber layer (RNFL) thickness measurements with spectral domain optical coherence tomography (SD-OCT). For eyes converting to glaucoma, estimates of RGC counts were obtained at the time (within ± 3 months) of the first abnormal visual field, representing the time of earliest detection of visual field losses. MAIN OUTCOME MEASURES: Estimates of RGC counts in eyes converting to glaucoma versus healthy eyes. RESULTS: The average RGC count estimate in the eyes with early visual field defects was 652057 ± 115829 cells, which was significantly lower than the average of 910 584 ± 142 412 cells found in healthy eyes (P < 0.001). Compared with the average number of RGCs in the healthy group, glaucomatous eyes had an average RGC loss of 28.4%, ranging from 6% to 57%, at the time of the earliest visual field defect on SAP. Retinal ganglion cell counts performed significantly better than the SD-OCT average RNFL thickness parameter in discriminating glaucomatous from healthy eyes with receiver operating characteristic curve areas of 0.95 ± 0.02 versus 0.88 ± 0.03, respectively (P = 0.001). CONCLUSIONS: Glaucomatous eyes with the earliest detectable visual field loss on automated perimetry may already show substantial loss of RGCs. Empirical estimates of RGC counts combining structural and functional tests agreed closely with previous histologic reports on the number of RGCs associated with early visual fields defects on SAP.

A combined index of structure and function for staging glaucomatous damage.

OBJECTIVES: To present and evaluate a new combined index of structure and function (CSFI) for staging and detecting glaucomatous damage. METHODS: Observational study including 333 glaucomatous eyes (295 with perimetric glaucoma and 38 with preperimetric glaucoma) and 330 eyes of healthy subjects. All the eyes were tested with standard automated perimetry and spectral domain optical coherence tomography within 6 months. Estimates of the number of retinal ganglion cells (RGCs) were obtained from standardautomated perimetry and spectral domain optical coherence tomography and a weighted averaging scheme was used to obtain a final estimate of the number of RGCs for each eye. The CSFI was calculated as the percent loss of RGCs obtained by subtracting estimated from expected RGC numbers. The performance of the CSFI for discriminating glaucoma from normal eyes and the different stages of disease was evaluated by receiver operating characteristic curves. RESULTS: The mean CSFI, representing the mean estimated percent loss of RGCs, was 41% and 17% in the perimetric and preperimetric groups, respectively (P.001). They were both significantly higher than the mean CSFI in the healthy group (P.001). The CSFI had larger receiver operating characteristic curve areas than isolated indexes of structure and function for detecting perimetric and preperimetric glaucoma and differentiating among early, moderate, and advanced stages of visual field loss. CONCLUSION: An index combining structure and function performed better than isolated structural and functional measures for detection of perimetric and preperimetric glaucoma as well as for discriminating different stages of the disease.

Diagnosing preperimetric glaucoma with spectral domain optical coherence tomography.

PURPOSE: To evaluate the diagnostic accuracy of spectral domain optical coherence tomography (SD-OCT) for detection of preperimetric glaucoma and compare it with the performance of confocal scanning laser ophthalmoscopy (CSLO). DESIGN: Cohort study. PARTICIPANTS: A cohort of 134 eyes of 88 glaucoma suspects based on the appearance of the optic disc. METHODS: Patients were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS). All eyes underwent retinal nerve fiber layer (RNFL) imaging with Spectralis SD-OCT (Heidelberg Engineering, Carlsbad, CA) and topographic imaging with Heidelberg Retinal Tomograph III (HRT-III) (Heidelberg Engineering) CSLO within 6 months of each other. All patients had normal visual fields at the time of imaging and were classified on the basis of history of documented stereophotographic evidence of progressive glaucomatous change in the appearance of the optic nerve occurring before the imaging sessions. MAIN OUTCOME MEASURES: Areas under the receiver operating characteristic curves (AUCs) were calculated to summarize diagnostic accuracies of the SD-OCT and CSLO. Likelihood ratios (LRs) were reported using the diagnostic categorization provided by each instrument after comparison to its normative database. RESULTS: Forty-eight eyes of 42 patients had evidence of progressive glaucomatous change and were included in the preperimetric glaucoma group. Eighty-six eyes of 46 patients without any evidence of progressive glaucomatous change followed untreated for an average of 14.0 ± 3.6 years were included in the control group. The parameter with the largest AUC obtained with the SD-OCT was the temporal superior RNFL thickness (0.88 ± 0.03), followed by global RNFL thickness (0.86 ± 0.03) and temporal inferior RNFL thickness (0.81 ± 0.04). The parameter with the largest AUC obtained with the CSLO was rim area (0.72 ± 0.05), followed by rim volume (0.71 ± 0.05) and linear cup-to-disk ratio (0.66 ± 0.05). Temporal superior RNFL average thickness measured by SD-OCT performed significantly better than rim area measurements from CSLO (0.88 vs. 0.72; P=0.008). Outside normal limits results for SD-OCT parameters were associated with strongly positive LRs. CONCLUSIONS: The RNFL assessment with SD-OCT performed well in detecting preperimetric glaucomatous damage in a cohort of glaucoma suspects and had a better performance than CSLO.

A combined index of structure and function for staging glaucomatous damage.

OBJECTIVES: To present and evaluate a new combined index of structure and function (CSFI) for staging and detecting glaucomatous damage. METHODS: Observational study including 333 glaucomatous eyes (295 with perimetric glaucoma and 38 with preperimetric glaucoma) and 330 eyes of healthy subjects.All the eyes were tested with standard automated perimetry and spectral domain optical coherence tomography within 6 months. Estimates of the number of retinal ganglion cells (RGCs) were obtained from standard automated perimetry and spectral domain optical coherence tomography and a weighted averaging scheme was used to obtain a final estimate of the number of RGCs for each eye. The CSFI was calculated as the percent loss of RGCs obtained by subtracting estimated from expected RGC numbers. The performance of the CSFI for discriminating glaucoma from normal eyes and the different stages of disease was evaluated by receiver operating characteristic curves. RESULTS: The mean CSFI, representing the mean estimated percent loss of RGCs, was 41% and 17% in theperimetric and preperimetric groups, respectively(P.001). They were both significantly higher than the mean CSFI in the healthy group (P.001). The CSFI had larger receiver operating characteristic curve areas than isolated indexes of structure and function for detecting perimetric and preperimetric glaucoma and differentiating among early, moderate, and advanced stages of visual field loss. CONCLUSION: An index combining structure and function performed better than isolated structural and functional measures for detection of perimetric and preperimetric glaucoma as well as for discriminating different stages of the disease.