RESUMO
Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.
Assuntos
Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Aberto , Humanos , Predisposição Genética para Doença , Glaucoma de Ângulo Aberto/genética , População Negra/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Minimally invasive glaucoma surgery (MIGS) refers to a group of procedures generally characterized by an ab interno approach, minimal trauma to ocular tissue, moderate efficacy, an excellent safety profile, and rapid recovery. The number of MIGS procedures continues to increase, and their use has become widespread among glaucoma and cataract specialists. Standardization of the methodology and reporting of clinical endpoints in MIGS investigations enhances interpretation and comparison across different studies. The assessment of surgical interventions should not only consider statistical significance, but also whether the outcome is meaningful to patients. Minimal clinically important difference (MCID) is defined as the smallest change in a treatment outcome that is considered beneficial for an individual patient and prompts a change in their clinical management, and expert consensus is an accepted approach to determine the MCID. The American Academy of Ophthalmology's Glaucoma Preferred Practice Pattern Panel is an expert panel that develops guidelines identifying characteristics and components of quality eye care. The panel recommends that the cumulative probability of surgical success at 2 years with Kaplan-Meier survival analysis be used as the primary efficacy endpoint in MIGS studies. The panel suggests that surgical success for standalone MIGS be defined as intraocular pressure (IOP) ≤ 21 mmHg and reduced ≥ 20% from baseline without an increase in glaucoma medications, additional laser or incisional glaucoma surgery, loss of light perception vision, or hypotony. The proposed MCID for the cumulative probability of success of standalone MIGS at 2 years is 50%. The panel recommends that surgical success for MIGS combined with cataract extraction with intraocular lens implantation (CE-IOL) be defined as a decrease in glaucoma medical therapy ≥ 1 medication from baseline without an increase in IOP, or IOP ≤ 21 mmHg and reduced ≥ 20% from baseline without an increase in glaucoma medications, additional laser or incisional glaucoma surgery, loss of light perception vision, or hypotony. The suggested MCID for the cumulative probability of success for CE-IOL/MIGS at 2 years is 65%.
RESUMO
SIGNIFICANCE: The glaucoma question prompt list/video intervention was well received by patients. Eighty-seven percent of patients recommended that other patients should watch the educational video before their visits, and 89% said that other patients should complete the question prompt list before visits. PURPOSE: The objectives of this study were to (a) describe patient feedback on a glaucoma question prompt list/video intervention designed to motivate African American patients to be more engaged during visits and (b) examine patient demographics associated with acceptance of the intervention. METHODS: We are conducting a randomized controlled trial of a glaucoma question prompt list/video intervention. African American patients with glaucoma were enrolled and assigned to a control group or an intervention group where they watched a video emphasizing the importance of asking questions and received a prompt list to complete before visits. All patients were interviewed after visits and are being followed up for 12 months. RESULTS: One hundred eighty-nine African American patients with glaucoma were enrolled into the larger trial. Of the 93 patients randomized to the intervention group, 89% said that patients should complete the prompt lists before visits, and 87% recommended that patients should watch the video before visits. Older patients were significantly less likely to believe that other patients should watch the video before their visits (t = -3.7, P = .04). Patients with fewer years of education were significantly more likely to rate the video as being more useful than patients with more years of education (Pearson correlation, -0.27; P = .01). Patients who reported being less adherent on the visual analog scale were more likely to rate the video as being more useful (Pearson correlation, -0.23; P = .03). CONCLUSIONS: This study demonstrates that the question prompt list/video was accepted by the majority of African American patients who received the intervention.
Assuntos
Negro ou Afro-Americano , Glaucoma , Humanos , Glaucoma/terapia , PacientesRESUMO
SIGNIFICANCE: The developed video can be accessed by African American patients with glaucoma from across the United States on YouTube to learn why it is important to ask eye care providers any questions they might have about glaucoma and/or its treatment. PURPOSE: Our objective was to develop an educational video for African Americans with glaucoma to watch before their ophthalmology office visits to help motivate them to be actively involved in their care. METHODS: The Social Cognitive Theory guided the development of the video. We conducted three focus groups with African American patients with glaucoma and three focus groups with providers who care for African American patients with glaucoma. The research team reviewed the transcripts of the focus groups and then developed a plan for video production. RESULTS: The themes that both patients and providers felt should be covered in the video to motivate patient question-asking included the following: what is glaucoma, glaucoma treatment, glaucoma testing, and treatment adherence. Based on focus group results, the resulting video had one male African American physician and four African American patients covering the themes that emerged. CONCLUSIONS: Ophthalmologists and African Americans with glaucoma gave us excellent insight into developing videos to increase patient involvement during their visits.
Assuntos
Negro ou Afro-Americano/etnologia , Glaucoma/etnologia , Educação de Pacientes como Assunto/métodos , Participação do Paciente , Gravação em Vídeo , Idoso , Comunicação , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Visita a Consultório Médico , Oftalmologistas , Relações Médico-Paciente , Estados UnidosRESUMO
PURPOSE: To determine the incidence of open-angle glaucoma (OAG) and its risk factors in the Tema Eye Survey in Ghana, West Africa. DESIGN: Longitudinal, observational population-based study. PARTICIPANTS: One thousand two hundred five of 1500 participants 40 years of age or older selected randomly from 5603 participants originally drawn from the population and who had undergone a baseline examination. METHODS: All participants underwent baseline and follow-up ophthalmologic examinations 8 years apart. Glaucoma diagnosis was determined based on the International Society for Geographical and Epidemiologic Ophthalmology criteria. MAIN OUTCOME MEASURES: Incidence and odds ratio (OR). RESULTS: The response rate was 80.3%. Of 1101 nonglaucomatous participants at baseline who had complete follow-up data, 4.6% (95% confidence interval [CI], 3.7%-5.2%) demonstrated OAG over the 8-year period, or 0.58% (95% CI, 0.4%-0.8%) per year. The 8-year incidence increased with age from 3.1% in those 40 to 49 years old to 7.0% in those 60 to 69 years old. Baseline risk factors for incident OAG were male gender (OR, 2.1; 95% CI, 1.1-4.0; P = 0.025), older age relative to those 40 to 49 years old (those 50-50 years old: OR, 2.6; 95% CI, 1.2-5.7; those 60-69 years old: OR, 4.3; 95% CI, 2.0-8.8; and for those 70 years of age and older: OR, 6.3; 95% CI, 2.6-15.4; all P < 0.001), higher intraocular pressure (IOP; OR, 1.4; 95% CI, 1.1-1.8; P < 0.001), larger vertical cup-to-disc ratio (OR, 5.8; 95% CI, 5.2-6.6; P < 0.001), and thinner central cornea (OR, 1.2; 95% CI, 1.03-1.5; P = 0.013). A separate analysis performed with central corneal thickness-based IOP correction did not change the outcome of the associative model of incident glaucoma. CONCLUSIONS: The incidence of OAG is higher in this population than reported in nonblack populations outside Africa. This is important not only in Ghana and probably other West African countries but also wherever people of the West African diaspora reside. These data enhance our understanding of the epidemiologic factors of OAG in this setting and may serve as reference for public health policy and planning.
Assuntos
Glaucoma de Ângulo Aberto/epidemiologia , Inquéritos Epidemiológicos/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , População Negra/estatística & dados numéricos , Feminino , Gana/epidemiologia , Glaucoma de Ângulo Aberto/diagnóstico , Gonioscopia , Humanos , Incidência , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Distribuição por Sexo , Microscopia com Lâmpada de Fenda , Tonometria Ocular , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologiaRESUMO
SIGNIFICANCE: Glaucoma patients express a strong need for practical instruction on instilling eye drops correctly. To maximize the benefit of a video intervention to improve eye drop technique, patients recommend that video education be provided both in the clinic setting and online. PURPOSE: The purposes of this study were to (1) describe glaucoma patients' perspectives on how to improve an online eye drop technique video and how to disseminate it to other glaucoma patients and (2) examine how these perspectives differ across demographics. METHODS: Glaucoma patients (N = 43) who viewed an online eye drop technique educational video as part of a randomized controlled trial were interviewed to assess their overall rating of the video on a 4-point scale, with whom they had watched the video, whether they would recommend the video to others, how the video helped them, how they would recommend improving the video, and how they would like the video to be disseminated to other glaucoma patients. RESULTS: Patients' mean (SD) rating of the video was 3.4 (0.8), with a higher mean rating of 3.8 among African Americans (P = .02). All 43 patients said that they would recommend that others watch the video. Patients most commonly said that the video helped them learn to block the tear duct correctly, put the cap down on its side, mix the medication correctly, and close the eye after instillation. Patients preferred viewing the video in the doctor's office examination room and a website. CONCLUSIONS: Eye drop technique videos should be disseminated in the doctor's office and online. Health systems that integrate educational videos into their everyday practice may be able to use technique videos to improve patient technique at low cost and little time burden to the provider.
Assuntos
Anti-Hipertensivos/administração & dosagem , Glaucoma de Ângulo Aberto/tratamento farmacológico , Soluções Oftálmicas/administração & dosagem , Educação de Pacientes como Assunto/métodos , Preferência do Paciente/estatística & dados numéricos , Gravação de Videoteipe/estatística & dados numéricos , Administração Oftálmica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Comunicação em Saúde , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Autoadministração , Adulto JovemRESUMO
Importance: Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives: To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants: A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14â¯917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures: Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures: Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results: A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-ß A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14â¯917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance: In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , População Negra/genética , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Aberto/etnologia , Glaucoma de Ângulo Aberto/genética , Polimorfismo de Nucleotídeo Único , Idoso , Peptídeos beta-Amiloides/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Imuno-Histoquímica , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
PURPOSE OF REVIEW: Since its introduction in ophthalmology, optical coherence tomography (OCT) has undergone significant advances in imaging protocols, algorithms, and addition of new parameters which have maximized its potential for diagnosing, evaluating the response to treatment, and assessing the progression of various ocular diseases, including glaucoma. This review provides an update on recent developments in OCT with respect to the management of glaucoma. RECENT FINDINGS: Most recent notable developments include the introduction of the minimum distance band, which is a three-dimensional optic nerve head parameter, and Swept-Source OCT with its single wide-field scanning capability. The introduction of OCT angiography provides additional structural and functional measures for glaucoma management. Adaptive optics helps visualize individual RNFL bundles and measure their widths. SUMMARY: Continued improvements in OCT technology is both enhancing our understanding of glaucoma and improving our ability to manage the disease.
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Glaucoma/diagnóstico por imagem , Fibras Nervosas/patologia , Disco Óptico/diagnóstico por imagem , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Animais , Angiografia por Tomografia Computadorizada/métodos , Humanos , Imageamento Tridimensional/métodosRESUMO
PURPOSE OF REVIEW: To describe the current state of knowledge regarding glaucoma patients' eye drop technique, interventions attempting to improve eye drop technique, and methods for assessing eye drop technique. RECENT FINDINGS: In observational studies, between 18.2 and 80% of patients contaminate their eye drop bottle by touching their eye or face, 11.3-60.6% do not instill exactly one drop, and 6.8-37.3% miss the eye with the drop. Factors significantly associated with poorer technique include older age, lack of instruction on eye drop technique, female sex, arthritis, more severe visual field defect, lack of positive reinforcement to take eye drops, lower educational level, low self-efficacy, and being seen at a clinic rather than a private practice. Among intervention studies, four of five studies using a mechanical device and three of four studies using educational interventions to improve technique showed positive results, but none of the studies were randomized controlled trials. SUMMARY: Poor eye drop technique is a significant impediment to achieving good control of intraocular pressure in glaucoma. Both mechanical device interventions and educational interventions offer promise to improve patients' technique, but studies with stronger designs need to be done followed by introduction into clinical practice.
Assuntos
Administração Oftálmica , Anti-Hipertensivos/administração & dosagem , Glaucoma/tratamento farmacológico , Soluções Oftálmicas/administração & dosagem , Embalagem de Medicamentos , Humanos , Pressão Intraocular/efeitos dos fármacos , Adesão à Medicação , Educação de Pacientes como Assunto , Tonometria OcularRESUMO
Timely detection of glaucomatous progression is crucial in the delivery of glaucoma care. Clinical judgment may be used to make this assessment, but relatively modest agreement among practitioners supports the use of complementary methods. Event-based analyses take into account expected localized test-retest variabilities in sensitivity, and trend-based analyses are helpful for determining and predicting overall visual function. Landmark clinical trials have used various visual field progression criteria as end points with variable performances. Short- and long-term fluctuations as well as inadequate testing frequency are limitations in visual field analysis for glaucomatous progression. Ongoing improvements in statistical techniques as well as incorporation of functional and structural measures into a single model likely will lead to an enhanced ability to detect glaucomatous progression and will allow for more timely and appropriate therapy.
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Glaucoma de Ângulo Aberto/diagnóstico , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Transtornos da Visão/diagnóstico , Testes de Campo Visual/métodos , Campos Visuais , Progressão da Doença , Humanos , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologiaRESUMO
PURPOSE OF REVIEW: Optical coherence tomography (OCT) aids in the diagnosis and long-term monitoring of various ocular diseases, including glaucoma. Initially, the retinal nerve fiber layer was the only OCT structural parameter used in glaucoma. Subsequent research has resulted in more retinal and optic nerve head parameters. In addition, OCT is being investigated for its ability to assess ocular hemodynamics. This review summarizes these spectral domain-optical coherence tomography (SDOCT) parameters in the context of glaucoma. RECENT FINDINGS: Several new SDOCT retinal nerve fiber layer, optic nerve head, and macular parameters with good glaucoma diagnostic ability have been added to existing ones recently. The combination of SDOCT and Doppler or angiography has also resulted in hemodynamic parameters that may prove to be useful in the functional assessment in glaucoma. SUMMARY: OCT technology is advancing not only as a tool for structural assessment, but also as a multimodality tool to assess both structure and function to enhance our understanding of glaucoma, and ultimately clinical decisions.
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Glaucoma/diagnóstico , Tomografia de Coerência Óptica , Progressão da Doença , Hemodinâmica , Humanos , Disco Óptico , RetinaRESUMO
PURPOSE: To compare the 5-year outcomes of the Ahmed FP7 Glaucoma Valve (AGV) (New World Medical, Cucamonga, CA) and the Baerveldt 101-350 Glaucoma Implant (BGI) (Abbott Medical Optics, Abbott Park, IL) for the treatment of refractory glaucoma. DESIGN: Multicenter, randomized, controlled clinical trial. PARTICIPANTS: A total of 276 patients, including 143 in the AGV group and 133 in the BGI group. METHODS: Patients aged 18 to 85 years with previous intraocular surgery or refractory glaucoma and intraocular pressure (IOP) of ≥18 mmHg in whom glaucoma drainage implant (GDI) surgery was planned were randomized to implantation of an AGV or a BGI. MAIN OUTCOME MEASURES: Surgical failure, IOP, visual acuity (VA), use of glaucoma medications, and complications. RESULTS: At 5 years, IOP (mean ± standard deviation [SD]) was 14.7±4.4 mmHg in the AGV group and 12.7±4.5 mmHg in the BGI group (P = 0.015). The number of glaucoma medications in use at 5 years (mean ± SD) was 2.2±1.4 in the AGV group and 1.8±1.5 in the BGI group (P = 0.28). The cumulative probability of failure during 5 years of follow-up was 44.7% in the AGV group and 39.4% in the BGI group (P = 0.65). The number of subjects failing because of inadequately controlled IOP or reoperation for glaucoma was 46 in the AGV group (80% of AGV failures) and 25 in the BGI group (53% of BGI failures; P = 0.003). Eleven eyes in the AGV group (20% of AGV failures) experienced persistent hypotony, explantation of implant, or loss of light perception compared with 22 eyes (47% of failures) in the BGI group. Change in logarithm of the minimum angle of resolution VA (mean ± SD) at 5 years was 0.42±0.99 in the AGV group and 0.43±0.84 in the BGI group (P = 0.97). CONCLUSIONS: Similar rates of surgical success were observed with both implants at 5 years. The BGI produced greater IOP reduction and a lower rate of glaucoma reoperation than the AGV, but the BGI was associated with twice as many failures because of safety issues.
Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Feminino , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Implantação de Prótese , Reoperação , Tonometria Ocular , Trabeculectomia , Falha de Tratamento , Resultado do Tratamento , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To explore the association between peripapillary atrophy (PPA) area and conversion from ocular hypertension (OHT) to glaucoma. DESIGN: Prospective, longitudinal cohort study of cases and controls. PARTICIPANTS: We included 279 age-matched and follow-up time-matched eyes with OHT that converted to glaucoma and 279 eyes with OHT that did not convert to glaucoma. METHODS: Initial and last acceptable optic disc photos were analyzed. Disc, α-zone, and ß-zone PPA were traced independently by 2 trained readers and their areas were measured with Photoshop. The α-zone and ß-zone areas were expressed as a percentage of optic disc area. MAIN OUTCOME MEASURES: α-Zone and ß-zone PPA size over time. RESULTS: Intraclass correlation coefficients (ICCs) demonstrated that readers had good agreement on disc area (ICC = 0.97) and ß-zone (ICC = 0.82), but not α-zone (ICC = 0.48). The ß-zone, as a percentage of disc area, increased in size (P < 0.001) in both eyes with incident primary open-angle glaucoma (mean, 10.6%; standard deviation, 22.6%) and matched controls (mean, 10.1%; standard deviation, 33.7) over follow-up (mean, 12.3 years). The increase in size did not differ between cases and controls (P = 0.82). Enlargement of the ß-zone was not correlated with follow-up time (P = 0.39). CONCLUSIONS: The results did not show a difference in size of the ß-zone at baseline between eyes that proceed to develop glaucoma and those that do not. Moreover, the ß-zone enlarges equally in case and control eyes during follow-up.
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Glaucoma de Ângulo Aberto/diagnóstico , Hipertensão Ocular/diagnóstico , Atrofia Óptica/diagnóstico , Disco Óptico/patologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Pressão Intraocular , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fotografação , Estudos Prospectivos , Reprodutibilidade dos Testes , Tomografia de Coerência Óptica , Tonometria Ocular , Transtornos da Visão/diagnóstico , Campos VisuaisRESUMO
PURPOSE: To study the performance of the Matrix perimeter compared with the Humphrey Field Analyzer II (HFA) with the Swedish Interactive Thresholding Algorithm over the range of contrast sensitivities each machine could estimate. METHODS: Fifty stable glaucoma subjects at various stages of disease and three normal subjects had visual fields testing done on five different days within 8 weeks with both perimeters. Intraclass correlation coefficient of mean deviation, pattern standard deviation, and the SD of repeat measurements were evaluated. The repeatability of the sensitivity estimates at individual locations and global indices was quantified, as well as their dependence on disease severity. The relationship between sensitivity determinations with the two instruments was explored (principal curve analysis). RESULTS: Mean deviation on the HFA ranged from -31 to +2.5 dB. The mean deviation and pattern standard deviation had intraclass correlation coefficients above 0.90 for both instruments. Over most of the useful range (above 20 dB on the HFA), a difference of 1 dB for the Matrix corresponded to a difference of 2 dB for the HFA. The SD of repeat measurements increased with disease severity with HFA, but not with Matrix, except that values of 12 or 34 dB were highly variable on repeat. Variability was reduced for both HFA and Matrix when duplicate sensitivity values were used. A single Matrix test provided only 15 possible sensitivity values, unevenly spaced, but the average of duplicate measurements provided more numerous sensitivity values. A learning effect was detected for Matrix. CONCLUSIONS: The decibel values reported by the two machines are not equivalent. Variability of sensitivity determinations is affected more by the sensitivity level with HFA than with Matrix. Duplicate measurements for baseline and follow-up evaluation could be important, especially for Matrix. Further information on learning effects is needed, as is commercially available progression software for Matrix.
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Glaucoma/diagnóstico , Transtornos da Visão/diagnóstico , Testes de Campo Visual/instrumentação , Campos Visuais/fisiologia , Adulto , Idoso , Algoritmos , Sensibilidades de Contraste , Progressão da Doença , Eletrorretinografia , Feminino , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia de Coerência Óptica , Transtornos da Visão/fisiopatologia , Testes de Campo Visual/métodosRESUMO
Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], ORâ=â0.69 [95%CI 0.63-0.75], pâ=â1.86×10⻹8), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], ORâ=â1.32 [95%CI 1.21-1.43], pâ=â3.87×10⻹¹). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], ORâ=â0.58 [95% CI 0.50-0.67], pâ=â1.17×10⻹²) and a probable regulatory region on 8q22 (rs284489 [G], ORâ=â0.62 [95% CI 0.53-0.72], pâ=â8.88×10⻹°). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], ORâ=â0.59 [95% CI 0.41-0.87], pâ=â0.004 and rs284489 [G], ORâ=â0.76 [95% CI 0.54-1.06], pâ=â0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted pâ=â0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma.
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Síndrome de Exfoliação/genética , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Aberto/genética , Degeneração Neural , Fator de Crescimento Transformador beta , Alelos , Cromossomos Humanos Par 8 , Cromossomos Humanos Par 9 , Proteínas de Homeodomínio/genética , Humanos , Degeneração Neural/genética , Degeneração Neural/patologia , Nervo Óptico/patologia , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante , RNA não Traduzido/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. Using genome-wide association single-nucleotide polymorphism data from the Glaucoma Genes and Environment study and National Eye Institute Glaucoma Human Genetics Collaboration comprising 3,108 cases and 3,430 controls, we assessed biologic pathways as annotated in the KEGG database for association with risk of POAG. After correction for genic overlap among pathways, we found 4 pathways, butanoate metabolism (hsa00650), hematopoietic cell lineage (hsa04640), lysine degradation (hsa00310) and basal transcription factors (hsa03022) related to POAG with permuted p < 0.001. In addition, the human leukocyte antigen (HLA) gene family was significantly associated with POAG (p < 0.001). In the POAG subset with normal-pressure glaucoma (NPG), the butanoate metabolism pathway was also significantly associated (p < 0.001) as well as the MAPK and Hedgehog signaling pathways (hsa04010 and hsa04340), glycosaminoglycan biosynthesis-heparan sulfate pathway (hsa00534) and the phenylalanine, tyrosine and tryptophan biosynthesis pathway (hsa0400). The butanoate metabolism pathway overall, and specifically the aspects of the pathway that contribute to GABA and acetyl-CoA metabolism, was the only pathway significantly associated with both POAG and NPG. Collectively these results implicate GABA and acetyl-CoA metabolism in glaucoma pathogenesis, and suggest new potential therapeutic targets.
Assuntos
Acetilcoenzima A/metabolismo , Glaucoma de Ângulo Aberto/genética , Glaucoma/genética , Redes e Vias Metabólicas/genética , Ácido gama-Aminobutírico/metabolismo , Estudos de Casos e Controles , Análise por Conglomerados , Feminino , Predisposição Genética para Doença , Glaucoma/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Humanos , Pressão Intraocular/genética , Masculino , Modelos Genéticos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
PURPOSE: To compare 3-year outcomes and complications of the Ahmed FP7 Glaucoma Valve (AGV) (New World Medical, Cucamonga, CA) and the Baerveldt Glaucoma Implant (BGI) 101-350 (Abbott Medical Optics, Abbott Park, IL) for the treatment of refractory glaucoma. DESIGN: Multicenter, randomized, controlled clinical trial. PARTICIPANTS: A total of 276 patients: 143 in the AGV group and 133 in the BGI group. METHODS: Patients aged 18 to 85 years with refractory glaucoma and intraocular pressures (IOPs) ≥ 18 mmHg in whom an aqueous shunt was planned were randomized to an AGV or a BGI. MAIN OUTCOME MEASURES: The IOP, visual acuity (VA), supplemental medical therapy, complications, and failure (IOP >21 mmHg or not reduced by 20% from baseline, IOP <5 mmHg, reoperation for glaucoma or removal of implant, or loss of light perception vision). RESULTS: At 3 years, IOP (mean ± standard deviation) was 14.3 ± ± 4.7 mmHg (AGV group) and 13.1 ± 4.5 mmHg (BGI group) (P = 0.086) on 2.0 ± 1.4 and 1.5 ± 1.4 glaucoma medications, respectively (P = 0.020). The cumulative probabilities of failure were 31.3% (standard error [SE], 4.0%) (AGV) and 32.3% (4.2%) (BGI) (P = 0.99). Postoperative complications associated with reoperation or vision loss of >2 Snellen lines occurred in 24 patients (22%) (AGV) and 38 patients (36%) (BGI) (P = 0.035). The mean change in the logarithm of the minimum angle of resolution VA at 3 years was similar (AGV: 0.21 ± 0.88, BGI: 0.26 ± 0.74) in the 2 treatment groups at 3 years (P = 0.66). The cumulative proportion of patients (SE) undergoing reoperation for glaucoma before the 3-year postoperative time point was 14.5% (3.0%) in the AGV group compared with 7.6% (2.4%) in the BGI group (P = 0.053, log rank). The relative risk of reoperation for glaucoma in the AGV group was 2.1 times that of the BGI group (95% confidence interval, 1.0-4.8; P = 0.045, Cox proportional hazards regression). CONCLUSIONS: Implantation of the AGV was associated with the need for significantly greater adjunctive medication to achieve equal success relative to implantation of the BGI and resulted in a greater relative risk of reoperation for glaucoma. More subjects experienced serious postoperative complications in the BGI group than in the AGV group.
Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Pressão Intraocular/fisiologia , Implantação de Prótese , Adolescente , Adulto , Idoso , Anti-Hipertensivos/administração & dosagem , Feminino , Seguimentos , Glaucoma/tratamento farmacológico , Glaucoma/fisiopatologia , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Modelos de Riscos Proporcionais , Reoperação , Tonometria Ocular , Resultado do Tratamento , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To evaluate the glaucoma diagnostic performance of ganglion cell inner-plexiform layer (GCIPL) parameters used individually and in combination with retinal nerve fiber layer (RNFL) or optic nerve head (ONH) parameters measured with Cirrus HD-OCT (Carl Zeiss Meditec, Inc, Dublin, CA). DESIGN: Prospective cross-sectional study. PARTICIPANTS: Fifty patients with early perimetric glaucoma and 49 age-matched healthy subjects. METHODS: Three peripapillary RNFL and 3 macular GCIPL scans were obtained in 1 eye of each participant. A patient was considered glaucomatous if at least 2 of the 3 RNFL or GCIPL scans had the average or at least 1 sector measurement flagged at 1% to 5% or less than 1%. The diagnostic performance was determined for each GCIPL, RNFL, and ONH parameter as well as for binary or-logic and and-logic combinations of GCIPL with RNFL or ONH parameters. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR). RESULTS: Among GCIPL parameters, the minimum had the best diagnostic performance (sensitivity, 82.0%; specificity, 87.8%; PLR, 6.69; and NLR, 0.21). Inferior quadrant was the best RNFL parameter (sensitivity, 74%; specificity, 95.9%; PLR, 18.13; and NLR, 0.27), as was rim area (sensitivity, 68%; specificity, 98%; PLR, 33.3; and NLR, 0.33) among ONH parameters. The or-logic combination of minimum GCIPL and average RNFL provided the overall best diagnostic performance (sensitivity, 94%; specificity, 85.7%; PRL, 6.58; and NLR, 0.07) as compared with the best RNFL, best ONH, and best and-logic combination (minimum GCIPL and inferior quadrant RNFL; sensitivity, 64%; specificity, 100%; PLR, infinity; and NPR, 0.36). CONCLUSIONS: The binary or-logic combination of minimum GCIPL and average RNFL or rim area provides better diagnostic performances than those of and-logic combinations or best single GCIPL, RNFL, or ONH parameters. This finding may be clinically valuable for the diagnosis of early glaucoma.
Assuntos
Axônios/patologia , Técnicas de Diagnóstico Oftalmológico , Glaucoma/diagnóstico , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Pressão Intraocular , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Testes de Campo Visual , Campos Visuais/fisiologiaRESUMO
PURPOSE: The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further. DESIGN: Case-control study. PARTICIPANTS: We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls). METHODS: We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7 × 10(-4) was used to account for multiple comparisons. MAIN OUTCOME MEASURES: Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss. RESULTS: We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61 × 10(-7)). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59 × 10(-5)). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07 × 10(-4)), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men. CONCLUSIONS: CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.
Assuntos
Caveolina 1/genética , Caveolina 2/genética , Variação Estrutural do Genoma , Glaucoma de Ângulo Aberto/genética , Polimorfismo de Nucleotídeo Único , Transtornos da Visão/genética , Campos Visuais , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
PURPOSE OF REVIEW: To review the current literature regarding the effectiveness and risks of new surgeries that can be combined with phacoemulsification in the management of cataract and glaucoma. RECENT FINDINGS: Surgical options for concurrently managing cataract and glaucoma have expanded in recent years. Endoscopic cyclophotocoagulation, trabecular micro-bypass stent, ab interno trabeculectomy, and canaloplasty may be performed in conjunction with cataract extraction to provide additional intraocular pressure (IOP) reduction. Studies evaluating these new glaucoma procedures combined with phacoemulsification generally include retrospective case series without a comparison group. Because cataract surgery alone is associated with IOP reduction, the relative contribution of the glaucoma procedure in lowering IOP cannot be determined in these studies. Randomized clinical trials are needed to better evaluate the efficacy and safety of newer glaucoma procedures in combination with cataract surgery. SUMMARY: The newer glaucoma procedures appear less effective than trabeculectomy, but they are associated with a lower risk of surgical complications.