What is the Optimal Frequency of Visual Field Testing to Detect Rapid Progression Among Hypertensive Eyes?

PRCIS: We evaluated 16,351 visual field (VF) tests from Ocular Hypertension Treatment Study (OHTS) database and showed that more frequent testing resulted in a shorter time to detect glaucoma progression, with the best trade-off being the 6-month intervals for high-risk and 12 months for low-risk patients. PURPOSE: To investigate the effect of different testing intervals on time to detect visual field progression in eyes with ocular hypertension. METHODS: A total of 16,351 reliable 30-2 VF tests from 1575 eyes of the OHTS-1 observation arm with a mean (95% CI) follow-up of 4.8 (4.7-4.8) years were analyzed. Computer simulations (n = 10,000 eyes) based on mean deviation values and the residuals of risk groups (according to their baseline 5 y risk of developing primary open angle glaucoma: low, medium, and high risk) were performed to estimate time to detect progression with testing intervals of 4, 6, 12, and 24 months using linear regression. The time to detect VF progression ( P < 5%) at 80% power was calculated based on the mean deviation slope of -0.42 dB/year. We assessed the time to detect a -3 dB loss as an estimate of clinically meaningful perimetric loss. RESULTS: At 80% power, based on the progression of -0.42 dB/year, the best trade-off to detect significant rates of VF change to clinically meaningful perimetric loss in high, medium, and low-risk patients was 6, 6, and 12-month intervals, respectively. CONCLUSION: Given the importance of not missing the conversion to glaucoma, the frequency of testing used in OHTS (6 mo) was optimal for the detection of progression in high-risk patients. Low-risk patients could potentially be tested every 12 months to optimize resource utilization.

Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer Thickness for Diagnosing Early to Moderate Glaucoma.

PRCIS: In a cross-sectional study from a Brazilian multiracial population, minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness measurements from OCT showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes. PURPOSE: The purpose of this study is to compare the ability of MRW and peripapillary retinal nerve fiber layer thickness (RNFLT) measurements in discriminating early to moderate glaucoma from healthy eyes in a Brazilian population. METHODS: A total of 155 healthy controls and 118 patients with mild to moderate glaucoma (mean deviation >-12 dB) underwent MRW and RNFLT measurements with optical coherence tomography. Only 1 eye per patient was included in the analysis. A receiver operating characteristic (ROC) regression model was used to evaluate the diagnostic accuracy of MRW and RNFLT, whereas adjusting for age and Bruch membrane opening area. Sensitivities at fixed specificities of 95% were calculated for each parameter. RESULTS: Global RNFLT and MRW showed comparable area under the ROC curves [0.93 (0.91-0.96) and 0.93 (0.89-0.96), respectively; P =0.973]. Both parameters had similar sensitivities (75% vs. 74%, respectively; P =0.852) at a fixed specificity of 95%. The best sector for diagnosing glaucoma for both parameters was the temporal inferior sector, which showed an area under the ROC curve of 0.93 (0.87-0.96) for RNFLT and 0.91 (0.86-0.95) for MRW ( P =0.320). The temporal inferior sector showed similar sensitivities for RNFLT and MRW measurements (83% vs. 77%, respectively) at a fixed specificity of 95% (P =0.230). CONCLUSIONS: MRW and RNFLT measurements showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes in a Brazilian multiracial population.

Frequency of Optical Coherence Tomography Testing to Detect Progression in Glaucoma.

PRCIS: With high specificity and less variability than perimetry, more frequent testing resulted in shorter time to detect progression, though a 6-month testing interval provides a reasonable trade-off for following glaucoma patients using optical coherence tomography (OCT). PURPOSE: To investigate the time to detect progression in glaucomatous eyes using different OCT test intervals. MATERIALS AND METHODS: Participants with manifest glaucoma from the African Descent and Glaucoma Evaluation Study (ADAGES), a multicenter, prospective, observational cohort study, were included. A total of 2699 OCT tests from 171 glaucomatous and 149 normal eyes of 182 participants, with at least 5 tests and 2 years of follow-up, were analyzed. Computer simulations (n=10,000 eyes) were performed to estimate time to detect progression of global circumpapillary retinal nerve fiber layer thickness (cpRNFL) measured with OCT tests. Simulations were based on different testing paradigms (every 4, 6, 12, and 24 mo) and different rates of change (µm/year). Time to detect significant progression ( P <0.05) at 80% and 90% power were calculated for each paradigm and rate of cpRNFL change. RESULTS: As expected, more frequent testing resulted in shorter time to detect progression. Although there was clear disadvantage for testing at intervals of 24 versus 12 months (~22.4% time [25 mo] increase in time to progression detection) and when testing 12 versus 6 months (~22.1% time [20 mo] increase), the improved time to detect progression was less pronounced when comparing 6 versus 4 months (~11.5% time [10 mo] reduction). CONCLUSION: With high specificity and less variability than perimetry, a 6-month testing interval provides a reasonable trade-off for following glaucoma patients using OCT.

Glaucomatous Visual Field Progression in the African Descent and Glaucoma Evaluation Study (ADAGES): Eleven Years of Follow-up.

PURPOSE: To compare the rates of visual field (VF) progression between individuals of Black and White race and to investigate whether treatment effects may help explain differences previously reported between racial groups. DESIGN: Multicenter prospective observational cohort study. METHODS: Participants were patients in referral tertiary care glaucoma clinics with open angle glaucoma. Eyes were excluded who had <5 VF tests and <2 years of follow-up or any disease that could affect the optic nerve or the VF. The VF mean deviation (MD) slopes over time (dB/y) were calculated with linear regression models. Socioeconomic variables, rates of glaucoma surgery, medications, treated intraocular pressure (IOP), and central corneal thickness (CCT) were investigated. RESULTS: A total of 516 eyes were included with a mean (95% CI) follow-up time of 11.0 (range, 10.5-11.5) years and 15.0 (range, 14.1-15.8) visits. Participants of Black race were significantly younger (59.7 vs 66.9 years, P < .01) than those of White race. The mean CCT and socioeconomic variables were similar between Black and White groups (P = 0.20 and P = .56, respectively), as were treatment with topical medications (P = .90) and the rate of VF MD change (-0.24 [-0.31 to -0.17] dB/year vs -0.32 [-0.36 to -0.27], P = .11), despite higher treated mean IOP (14.9 [14.5 to 15.4] vs 14.0 [13.6 to 14.4] mm Hg, P = .03) and fewer trabeculectomies (29.5% vs 50.0%, P < .01) in the Black race group. CONCLUSIONS: Rates of VF progression were similar despite higher treated IOP in the Black race group. Mitigation of health access disparities in this study may have equalized previously reported different rates of VF progression between racial groups.

Primary glaucomas in adults: Epidemiology and public health-A review.

Glaucoma is a mixed group of optic neuropathies that lead to irreversible visual field loss and blindness if left untreated. It is estimated that 3.5% of the global population aged 40 to 80 years have any glaucoma, being the primary open-angle and the primary angle-closure glaucoma the most prevalent forms. Although the age-standardised prevalence of blindness caused by glaucoma has decreased substantially over the last decades, population growth and ageing impose many challenges in preventing glaucoma-related morbidities on a global level. In addition, difficulties in diagnoses and treatment, along with its chronic and irreversible nature, urge the development and implementation of innovative approaches in confronting the disease. This manuscript reviews recent literature related to the epidemiology of primary glaucomas in adults, the risk factors attributed to the development of the disease, and discuss challenges and potential solutions from a public health perspective.

Relationship between mean follow-up intraocular pressure, rates of visual field progression and current target intraocular pressure guidelines.

AIMS: To investigate if eyes presenting intraocular pressure (IOP) within the limits of current guideline-driven target IOP indeed experience slow rates of glaucomatous visual field (VF) progression. METHODS: A total of 8598 24-2 VF tests from 603 eyes from the African Descent and Glaucoma Evaluation Study with manifest glaucoma were included. The sample was split into three groups based on baseline VF mean deviation (MD): G1 (better than -5.0 dB), G2 (-5.0 to -10 dB) and G3 (worse than -10 dB). We investigated the relationship between existing target IOP guidelines and rates of MD progression in these groups. RESULTS: For stable eyes, the medians and IQR of the mean follow-up IOP were G1=15.0 mmHg (IQR: 13.1 to 17.7), G2=13.2 mmHg (IQR: 11.6 to 14.3) and G3=11.9 mmHg (IQR: 10.1 to 13.8) (p<0.01). When considering the mean follow-up IOP within the limits proposed by current guidelines, the median MD slopes were: -0.20 dB/y (IQR: -0.43 to -0.02) for G1<21 mmHg, -0.19 dB/y (IQR: -0.51 to -0.01) for G2<18 mmHg and -0.15 dB/y (IQR: -0.47 to 0.05) for G3<15 mmHg (p=0.63). There were no significant differences between racial groups. CONCLUSION: In a sample of patients with manifest glaucoma, despite substantial variability between eyes, adherence to treatment guidelines helped slow the rates of global VF progression at various stages of disease. TRIAL REGISTRATION NUMBER: clinicaltrials.gov Identifier: NCT00221923.

Clinical validation of a smartphone-based handheld fundus camera for the evaluation of optic nerve head / Validação clínica de um retinógrafo portátil acoplado a smartphone para avaliação da cabeça do nervo óptico

ABSTRACT Purpose: To compare the quality of retinal images captured with a smartphone-based, handheld fundus camera with that of retinal images captured with a commercial fundus camera and to analyze their agreement in determining the cup-to-disc ratio for a cohort of ophthalmological patients. Methods: A total of 50 patients from a secondary ophthalmic outpatient service center underwent a bilateral fundus examination under mydriasis with a smartphone-based, handheld fundus camera and with a commercial fundus camera (4 images/patient by each). Two experienced ophthalmologists evaluated all the fundus images and graded them on the Likert 1-5 scale for quality. Multivariate regression analyses was then performed to evaluate the factors associated with the image quality. Two masked ophthalmologists determined the vertical cup-to-disc ratio of each fundus image, and both the intraobserver (between devices) and interobserver agreement between them was calculated. Results: Ninety-eight images from 49 patients were processed in this study for their quality analysis. Ten images from five patients (four from commercial fundus camera and one from smartphone-based, handheld fundus camera) were not included in the analyses due to their extremely poor quality. The medians [interquartile interval] of the image quality were not significantly different between those from the smartphone-based, handheld fundus camera and from the commercial fundus camera (4 [4-5] versus 4 [3-4] respectively, p=0.06); however, both the images captured with the commercial fundus camera and the presence of media opacity presented a significant negative correlation with the image quality. Both the intraobserver [intraclass correlation coefficient (ICC)=0.82, p<0.001 and 0.83, p<0.001, for examiners 1 and 2, respectively] and interobserver (ICC=0.70, p=0.001 and 0.81; p<0.001, for smartphone-based handheld fundus camera and commercial fundus camera, respectively) agreements were excellent and statistically significant. Conclusions: Our results thus indicate that the smartphone-based, handheld fundus camera yields an image quality similar to that from a commercial fundus camera, with significant agreement in the cup-to-disc ratios between them. In addition to the good outcomes recorded, the smartphone-based, handheld fundus camera offers the advantages of portability and low-cost to serve as an alternative for fundus documentation for future telemedicine approaches in medical interventions.

RESUMO Objetivo: Comparar a qualidade das imagens da retina capturadas com um retinógrafo portátil acoplado a um smartphone com aquelas adquiridas com um retinógrafo comercial padrão e analisar a concordância na determinação da relação escavação/ cabeça do nervo óptico em um coorte de pacientes de um serviço oftalmológico. Métodos: Cinquenta pacientes de um serviço oftalmológico secundário foram submetidos a uma avaliação do fundo de olho bilateral, sob midríase, utilizando o retinógrafo portátil acoplado a um smartphone e o retinógrafo comercial padrão (4 imagens por paciente). Dois oftalmologistas experientes avaliaram a qualidade de todas as imagens e atribuíram a elas uma pontuação entre 1 e 5, de acordo com a escala Likert. Os fatores relacionados a qualidade das imagens foram avaliados utilizando uma análise de regressão multivariada. Dois oftalmologistas determinaram de forma mascarada a relação da escavação/ cabeça do nervo óptico de cada imagem e a concordância intra e interobservador foi calculada. Resultados: Noventa e oito imagens de 49 pacientes foram utilizadas neste estudo para análise de qualidade. Dez imagens de cinco pacientes (quatro do retinógrafo comercial padrão e um do retinógrafo portátil acoplado a um smartphone) foram excluídas das análises de concordância devido à baixa qualidade das mesmas, mas foram considerados nas análises de qualidade. Dos cinco pacientes com imagens excluídas, quatro foram capturadas pelo retinógrafo comercial padrão e uma pelo retinógrafo portátil acoplado a um smartphone. As medianas (intervalo interquartil) da qualidade das imagens não apresentaram diferença estatística entre o retinógrafo portátil acoplado a um smartphone e o retinógrafo comercial padrão (4 [4-5] versus 4 [3-4] respectivamente, p=0.06). As imagens obtidas com o retinógrafo comercial padrão e o diagnóstico de opacidade de meios apresentou uma correlação negativa com a qualidade da imagem. As concordâncias intraobservador (ICC=0,82, p<0,001 e 0,83, p<0,001, para o examinador 1 e 2, respectivamente) e interobservador (ICC = 0,70, p=0,001 e 0,81, p<0.001, para o retinógrafo portátil acoplado a um smartphone e retinógrafo comercial padrão, respectivamente) foram excelentes e estatisticamente significativas. Conclusões: Nossos resultados sugerem que o retinógrafo portátil acoplado a um smartphone apresenta uma qualidade de imagem semelhante ao retinógrafo comercial padrão, com concordância significativa na análise da relação escavação-cabeça do nervo óptico. Além dos bons resultados apresentados, o retinógrafo portátil acoplado a um smartphone pode ser considerado uma alternativa portátil de baixo custo para documentação de retina em cenários futuros de telemedicina.

Clinical validation of a smartphone-based handheld fundus camera for the evaluation of optic nerve head.

PURPOSE: To compare the quality of retinal images captured with a smartphone-based, handheld fundus camera with that of retinal images captured with a commercial fundus camera and to analyze their agreement in determining the cup-to-disc ratio for a cohort of ophthalmological patients. METHODS: A total of 50 patients from a secondary ophthalmic outpatient service center underwent a bilateral fundus examination under mydriasis with a smartphone-based, handheld fundus camera and with a commercial fundus camera (4 images/patient by each). Two experienced ophthalmologists evaluated all the fundus images and graded them on the Likert 1-5 scale for quality. Multivariate regression analyses was then performed to evaluate the factors associated with the image quality. Two masked ophthalmologists determined the vertical cup-to-disc ratio of each fundus image, and both the intraobserver (between devices) and interobserver agreement between them was calculated. RESULTS: Ninety-eight images from 49 patients were processed in this study for their quality analysis. Ten images from five patients (four from commercial fundus camera and one from smartphone-based, handheld fundus camera) were not included in the analyses due to their extremely poor quality. The medians [interquartile interval] of the image quality were not significantly different between those from the smartphone-based, handheld fundus camera and from the commercial fundus camera (4 [4-5] versus 4 [3-4] respectively, p=0.06); however, both the images captured with the commercial fundus camera and the presence of media opacity presented a significant negative correlation with the image quality. Both the intraobserver [intraclass correlation coefficient (ICC)=0.82, p<0.001 and 0.83, p<0.001, for examiners 1 and 2, respectively] and interobserver (ICC=0.70, p=0.001 and 0.81; p<0.001, for smartphone-based handheld fundus camera and commercial fundus camera, respectively) agreements were excellent and statistically significant. CONCLUSIONS: Our results thus indicate that the smartphone-based, handheld fundus camera yields an image quality similar to that from a commercial fundus camera, with significant agreement in the cup-to-disc ratios between them. In addition to the good outcomes recorded, the smartphone-based, handheld fundus camera offers the advantages of portability and low-cost to serve as an alternative for fundus documentation for future telemedicine approaches in medical interventions.

Variability and Power to Detect Progression of Different Visual Field Patterns.

PURPOSE: To compare the variability and ability to detect visual field (VF) progression of 24-2, central 12 locations of the 24-2 and 10-2 VF tests in eyes with abnormal VFs. DESIGN: Retrospective, multisite cohort. PARTICIPANTS: A total of 52 806 24-2 and 11 966 10-2 VF tests from 7307 eyes from the Glaucoma Research Network database were analyzed. Only eyes with ≥ 5 visits and ≥ 2 years of follow-up were included. METHODS: Linear regression models were used to calculate the rates of mean deviation (MD) change (slopes), whereas their residuals were used to assess variability across the entire MD range. Computer simulations (n = 10 000) based on real MD residuals of our sample were performed to estimate power to detect significant progression (P < 5%) at various rates of MD change. MAIN OUTCOME MEASURES: Time required to detect progression. RESULTS: For all 3 patterns, the MD variability was highest within the -5 to -20 decibel (dB) range and consistently lower with the 10-2 compared with 24-2 or central 24-2. Overall, time to detect confirmed significant progression at 80% power was the lowest with 10-2 VF, with a decrease of 14.6% to 18.5% when compared with 24-2 and a decrease of 22.9% to 26.5% when compared with central 24-2. CONCLUSIONS: Time to detect central VF progression was reduced with 10-2 MD compared with 24-2 and C24-2 MD in glaucoma eyes in this large dataset, in part because 10-2 tests had lower variability. These findings contribute to current evidence of the potential value of 10-2 testing in the clinical management of patients with glaucoma and in clinical trial design.

Frequency and visual outcomes of ocular toxoplasmosis in an adult Brazilian population.

Although ocular toxoplasmosis is a leading cause of posterior uveitis worldwide, there is scarce information about the real-life frequency of ocular lesions, visual outcomes, and risk factors for poor prognosis. We conducted a community-based cross-sectional study with 721 adults living in Cássia dos Coqueiros, Southeast Brazil, consisted of visual acuity measurement, dilated ocular examination, a risk-factor questionnaire, and peripheral blood collection for anti-T. gondii serology. Presumed toxoplasmic lesions were recorded on video and analyzed by experienced and masked ophthalmologists. Ocular toxoplasmosis was determined if at least one suspected lesion was appointed by two graders in the presence of positive anti-T. gondii serology. Forty-eight eyes (n = 42 participants; 6.7% among those with positive anti-T. gondii serology) with ocular toxoplasmosis were found. Most lesions were single (n = 28; 58.3%), peripheral (n = 34; 77.1%) and unilateral (85.7% of participants); no active lesions were found. Older age was associated with lesions larger than one-disc diameter (p = 0.047), and lower social stratum (OR: 2.89; CI 1.2-6.97; p = 0.018) was associated with the presence of toxoplasmic lesions. Although there were no differences in visual acuity between participants and eyes with or without ocular lesions (p > 0.05), unilateral blindness associated with ocular toxoplasmosis was identified in a reduced number of individuals.

Retinal function after intravitreal injection of autologous bone marrow-derived mesenchymal stromal cells in advanced glaucoma.

PURPOSE: To report electroretinographic (ERG) findings in advanced glaucoma treated with a single intravitreal injection of bone marrow-derived mesenchymal stem cells (MSCs). METHODS: Intravitreal injection of autologous MSCs (1 × 106 cells) was performed in 2 eyes from 2 patients with open-angle glaucoma in advanced stage of optic neuropathy (ClinicalTrials.gov, NCT02330978, 01.05.2015): cup/disk ratio worse than 0.9, visual field mean deviation index lower than - 15 dB, visual acuity of light perception, but controlled intraocular pressure. ERG tests were recorded at baseline and week 1, 4 and 48 after injection, using DTL electrodes following the ISCEV standard: After dark adaptation, ERG was elicited using white flashes of 0.01 cd.s/m2 and 3.0 cd.s/m2, followed by 10-min light adaptation (30 cd/m2) and stimuli of 3.0 cd.s/m2 and 30 Hz flicker. RESULTS: Patients did not show improvement on visual acuity or visual field after treatment. At baseline, ERG responses showed typical findings for advanced glaucoma, with a- and b-wave amplitude and latency within normative range, but reduced photopic negative responses. No noteworthy changes were observed on ERG responses for both cases up to 1 week after treatment, but at day 15, one patient showed retinal detachment with proliferative vitreoretinopathy and was removed from the trial. The other patient kept ERG responses stable throughout study period. CONCLUSION: Although no ERG response changes were observed after MSCs injection in one case, the complication observed on the second one, along with the lack of visual function improvement, warrants further studies involving modified MSCs to treat ocular disorders, including glaucoma. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02330978- missed in pdf.

Disc-fovea Angle Is Associated With Visual Field Defect Location in Patients With Glaucoma.

PRECIS: The current study showed that glaucomatous eyes from patients with central visual field defects presented less negative disc-fovea angle compared with patients with peripheral defects. PURPOSE: The purpose of this study was to investigate the relationship between disc-fovea angle and visual field defect location in patients with glaucoma. MATERIALS AND METHODS: This was a cross-sectional study including glaucoma patients divided into isolated central and isolated peripheral scotoma groups. The main outcome measure was disc-fovea angle measurement between groups. Secondary outcomes included disc-fovea distance, vertical disc diameter, and fovea vertical deviation. RESULTS: We included 50 glaucoma patients (50 eyes; 27 with central scotoma and 23 with peripheral scotoma). Mean deviation from visual fields was -3.05±1.67 and -2.95±1.49 dB (P=0.829) (central and peripheral scotoma groups, respectively). We found that eyes in the central group had lower values of disc-fovea angle (-5.85±2.67 vs. -7.97±2.26 degrees, P=0.004), shorter disc-fovea distance (4.38±0.70 vs. 4.98±0.78 mm, P=0.006), and shorter fovea vertical deviation (-0.43±0.19 vs. -0.68±0.22 mm, P<0.001) compared with eyes in the peripheral group. CONCLUSIONS: This study showed an association between disc-fovea angle and central visual field defects in patients with glaucoma. Our findings suggest that eyes with a less negative disc-fovea angle should undergo a more careful investigation of the central visual field, even at early stages of the disease.

Electrophysiology in Glaucoma.

OBJECTIVES: Electrophysiological testing of the visual system has been continuously used in studies involving the evaluation of retinal ganglion cells and the diagnosis of glaucoma. This study aims to review the results of recent studies regarding the clinical applicability of electrophysiological tests to glaucoma. METHODS: A systematic review of the literature was carried out by 2 independent reviewers using the PubMed and EMBASE electronic databases, searching for articles published in English from January 1, 2014 to July 1, 2019 using a combination of the following keywords: ("glaucoma" OR "ocular hypertension") AND ("electrophysiolog" OR "electroretinogra" OR "ERG" OR "mfERG" OR "Pattern-reversal electroretinography" OR "PERG" OR "mfPERG" OR "photopic negative response" OR "pattern electroretinogram" OR "visual evoked potential" OR "multifocal electroretinography" OR "multifocal electroretinogram" OR "electro-oculography" OR "multifocal VEP" OR "mf-ERG"). A total of 38 studies were selected and the data of 30 of them were tabulated in this review. RESULTS: Among the 30 studies selected, the photopic negative response and the reversal pattern electroretinogram were found to be the major methods used to record the electroretinographic responses generated by the retinal ganglion cell. Their multifocal versions and the multifocal visual evoked potential were also proposed during this period. In general, the results underscored a consistent but general correlation between the amplitude and latency measures and routine tests for glaucoma, such as perimetry and optical coherence tomography. DISCUSSION: In agreement with previous reviews, clinical electrophysiological testing of the visual system reasonably matched with both the structural and functional analyses for glaucoma. No definitive indications of these tests have been established either at early detection or during follow-up of the disease, and easier protocols and better topographical correspondence with current glaucoma tests are warranted for their routine use.

Determining Optic Nerve Cupping Using Optical Coherence Tomography (OCT) Versus a New Electronic Mobile Device.

PURPOSE: We present a new device that may aid in glaucoma screening. The vertical cup-to-disc ratio (CDR) obtained from a new electronic mobile device (EMD) was compared with that obtained from a spectral-domain optical coherence tomography. In addition, results from examiner's evaluations were compared with the results mentioned above. METHODS: A single-masked study was performed to evaluate the CDR results from 110 eyes from 110 subjects whose ages ranged between 18 and 60 years (39±13 y old), of whom 66 (60%) were female individuals. Vertical CDR was analyzed 5 times with each device in a single visit and evaluated by 3 different ophthalmologists. The Spearman correlation test and Bland-Altman analysis were used to evaluate the correlation and agreement between methods. RESULTS: The CDR average using spectral-domain optical coherence tomography was 0.47±0.04, whereas the CDR average using EMD was 0.42±0.02. The clinical evaluation resulted in an average of 0.34±0.27. The Spearman test showed a strong correlation between vertical CDR obtained with both devices (r=0.8319; P<0.0001) and between EMD and the examiners (r=0.7156; P>0.001). Bland-Altman analysis showed good agreement between both devices as well as between EMD and the examiners (95% limits of agreement from -0.20 to 0.10 and from -0.15 to 0.30, respectively). CONCLUSIONS: We present a low-cost, reliable EMD that may serve as an alternative to subjectively measuring vertical CDR in face-to-face consultations and hence increase the general public's access to glaucoma screening. This may be especially useful for patients who live in remote areas.

Ex vivo evaluation of intravitreal mesenchymal stromal cell viability using bioluminescence imaging.

BACKGROUND: Bone marrow-derived mesenchymal stromal cell (MSC) therapy is a promising treatment for several degenerative ocular diseases; however, no reproducible method of monitoring these cells into the eye has been established. The aim of this study was to describe successful bioluminescence imaging (BLI) to detect viable luciferase-expressing MSC in the eye. METHODS: Human donor MSC in culture were transduced with 50 µl luciferase lentiviral vector (three viral particles/cell) prior to intraocular injection. Twenty-one right eyes of 21 rabbits were evaluated through BLI after receiving 1 × 106 luciferase-expressing MSC intravitreally. Contralateral eyes were injected with vehicle (phosphate-buffered saline (PBS)) and were used as controls. At seven different time points (1 h to 60 days), D-luciferin (40 mg/ml, 300 µl PBS) was injected in subsets of six enucleated eyes for evaluation of radiance decay through BLI analysis. CD90 and CD73 immunofluorescence was studied in selected eyes. RESULTS: Eyes injected with MSC showed high BLI radiance immediately after D-luciferin injection and progressive decay until 60 days. Mean BLI radiance measures from eyes with luciferase-expressing MSC were significantly higher than controls from 8 h to 30 days. At the thirtieth day, positive CD90- and CD73-expressing cells were observed only in the vitreous cavity of eyes injected with MSC. CONCLUSIONS: Viable MSC were identified in the vitreous cavity 1 month after a single injection. Our results confirmed BLI as a useful and reliable method to detect MSC injected into the eye globe.

Effects of the relative positioning between the disc-fovea angle and localized optic disc defects on the 10-2 visual field results in glaucoma.

PURPOSE: To investigate the effects of the foveal position relative to the optic disc on the 10-2 visual field (VF) results of glaucoma patients with localized inferotemporal neuroretinal rim defects (ITD). DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-seven eyes of 35 open-angle glaucoma (OAG) patients were included and divided into two groups based upon the presence (18 eyes) or not (39 eyes) of ITD. METHODS: Three different parameters obtained from a spectral domain optic coherence tomography (sdOCT) [disc-fovea angle (DFA), fovea vertical deviation (FVD) from midline, and the angular difference between the ITD border and the DFA (DAD)] were tested for their relationship with four 10-2 VF sectors: superior hemifield, superior edge, nasal edge, and superonasal arcuate. These relationships were tested with regression analyses with linear mixed effects models and random intercepts. MAIN OUTCOME MEASURES: Influences of DFA, FVD, and DAD on 10-2 VF sectors. RESULTS: Mean (±SD) values of DFA, FVD, and DAD were respectively: -5.05° ± 4.40°, -1346.6 um ± 1609.0 um, and 43.30° ± 17.33°. After adjustment for multiple comparisons, both FVD and DAD, but not DFA, were significantly associated with the severity of defects on the predefined VF sectors. Larger DAD values (third tertile: 54°-77°) showed higher coefficient estimate for the nasal edge sector sensitivities. CONCLUSIONS: The vertical foveal location and its position relative to the ITD was associated with loss of sensitivity at 10-2 VF locations in the superior hemifield. This association was significant but weak and was not seen using other conventional parameters that describe foveal position relative to the optic disc on sdOCT.

Life under pressure: The role of ocular cribriform cells in preventing glaucoma.

Primary open-angle glaucoma is a multifactorial blinding disease often impacting the two pressure-sensitive regions of the eye: the conventional outflow pathway and the optic nerve head (ONH). The connective tissues that span these two openings in the globe are the trabecular meshwork of the conventional outflow pathway and the lamina cribrosa of the ONH. Resident cribiform cells of these two regions are responsible for actively remodeling and maintaining their connective tissues. In glaucoma, aberrant maintenance of the juxtacanalicular tissues (JCT) of the conventional outflow pathway results in ocular hypertension and pathological remodeling of the lamina cribrosa results in ONH cupping, damaging retinal ganglion cell axons. Interestingly, cells cultured from the lamina cribrosa and the JCT of the trabecular meshwork have similarities regarding gene expression, protein production, plus cellular responses to growth factors and mechanical stimuli. This review compares and contrasts the current knowledge of these two cell types, whose health is critical for protecting the eye from glaucomatous changes. In response to pressure gradients across their respective cribiform tissues, the goal is to better understand and differentiate healthy from pathological behavior of these two cell types.

Effects of Swimming Goggles Wearing on Intraocular Pressure, Ocular Perfusion Pressure, and Ocular Pulse Amplitude.

PURPOSE: To evaluate changes in the ocular pulse amplitude (OPA) and ocular perfusion pressure (OPP), and investigate factors associated with intraocular pressure (IOP) elevation due to periorbital compression during swimming goggles (SG) use. METHODS: This cross-sectional study evaluated 35 eyes of 35 healthy volunteers during the wearing of a drilled SG. OPP calculation, Goldman applanation tonometry, and OPA measurements (using Pascal dynamic contour tonometer) were performed before, during, and after SG use. Scleral rigidity (calculated with Schiotz tonometry readings), orbital rim area, exophthalmometry, spherical equivalent, axial length, corneal thickness, and the goggles' rubber elastic force were considered in the multivariable analysis as potentially related to IOP changes. RESULTS: SG significantly increased IOP after 2 minutes of use (13.34±2.67 vs. 23.46±7.20 mm Hg, P<0.0001). After removal, IOP decreased significantly (10.20±5.85 mm Hg, P<0.0001). A inverse correlation between IOP and OPP differences was observed with the SG wearing (r=-0.57; P=0.0003). Mean OPA was significantly higher during compared with before SG wear (2.57±1.34 vs. 1.82±0.55 mm Hg for the timepoints 2 and 1, respectively; P=0.0064). Only orbital rim area (P=0.0052) and elastic force (P=0.0019) were significantly associated with IOP elevation. CONCLUSIONS: SG provoked acute IOP elevation and disturbance in the ocular hemodynamics, which was associated with larger orbital rim area and greater SG elastic force. These findings could have implications for subjects at high risk for glaucoma onset or progression.