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PURPOSE: To improve understanding of intraocular pressure (IOP) and its variance, this project identifies systemic and ocular characteristics of healthy eyes of adult volunteers including IOP variation, ocular biometrics, and aqueous humor dynamics (AHDs). These data serve as baseline controls for further studies from the Eye Dynamics and Engineering Network (EDEN) Consortium. DESIGN: Multicenter open-label clinical trial in healthy adults randomized to 1 week treatment with 2 approved glaucoma drugs in a crossover design. PARTICIPANTS: Among 135 healthy participants, 122 participants (aged 55.2 ± 8.8 years; 92 females, 30 males) completed the protocol. METHODS: Participants from the University of Michigan, Mayo Clinic, and University of Nebraska Medical Center underwent measurements of ocular biometrics, AHD, and IOP using 4 tonometers. Intraocular pressure data during 3 study visits without glaucoma medications were used in the analysis. The PhenX Toolkit survey acquired standardized data on medical history, surgical history, medications, smoking and alcohol exposures, and physical measures. MAIN OUTCOME MEASURES: The variability of IOP measurements within eyes was assessed as visit-to-visit IOP variation, within-visit IOP variation, and within-visit positional IOP variation. The concordance (or correlation) between eyes was also assessed. RESULTS: Average positional change of > 4.7 mmHg was detected with a range of 0.5-11.0 mmHg. Pearson correlation of IOP between eyes within a visit was 0.87 (95% confidence interval [CI], 0.82-0.91) for Goldmann applanation tonometry, 0.91 (95% CI, 0.88-0.94) for Icare rebound tonometry, and 0.91 (95% CI, 0.88-0.94) for pneumatonometry. There was a 4% to 12% asymmetric fluctuation of 3 mmHg or more between eyes between visits using rebound tonometry, 9% with Goldmann applanation tonometry, and 3% to 4% by pneumotonometry. The coefficient of variation between visits for the same eye ranged from 11.2% to 12.9% for pneumatonometry, from 13.6% to 17.4% for rebound tonometry, and 15.8% to 16.2% for Goldmann applanation tonometry. CONCLUSIONS: The current study from the EDEN Consortium describes measurement methods and data analyses with emphasis on IOP variability. Future papers will focus on changes in ocular biometrics and AHD with timolol or latanoprost treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
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Glaucoma , Masculino , Feminino , Humanos , Adulto , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Pressão Intraocular , Tonometria OcularRESUMO
Understanding aqueous outflow resistance at the level of aqueous veins has been a challenge to the management of glaucoma. This study investigated resolving the anatomies of aqueous veins and the textures of surrounding sclera using photoacoustic microscopy (PAM). A dual wavelength PAM system was established and validated using imaging phantoms, porcine and human globes perfused with an optical contrast agent ex vivo. The system shows lateral resolution of 8.23 µm and 4.70 µm at 1200â nm and 532â nm, respectively, and an axial resolution of 27.6 µm. The system is able to separately distinguish the aqueous veins and the sclera with high contrast in full circumference of the porcine and human globes.
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Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries. Identifying patients at high risk of progression to late AMD, the sight-threatening stage, is critical for clinical actions, including medical interventions and timely monitoring. Recently, deep-learning-based models have been developed and achieved superior performance for late AMD prediction. However, most existing methods are limited to the color fundus photography (CFP) from the last ophthalmic visit and do not include the longitudinal CFP history and AMD progression during the previous years' visits. Patients in different AMD subphenotypes might have various speeds of progression in different stages of AMD disease. Capturing the progression information during the previous years' visits might be useful for the prediction of AMD progression. In this work, we propose a Contrastive-Attention-based Time-aware Long Short-Term Memory network (CAT-LSTM) to predict AMD progression. First, we adopt a convolutional neural network (CNN) model with a contrastive attention module (CA) to extract abnormal features from CFPs. Then we utilize a time-aware LSTM (T-LSTM) to model the patients' history and consider the AMD progression information. The combination of disease progression, genotype information, demographics, and CFP features are sent to T-LSTM. Moreover, we leverage an auto-encoder to represent temporal CFP sequences as fixed-size vectors and adopt k-means to cluster them into subphenotypes. We evaluate the proposed model based on real-world datasets, and the results show that the proposed model could achieve 0.925 on area under the receiver operating characteristic (AUROC) for 5-year late-AMD prediction and outperforms the state-of-the-art methods by more than 3%, which demonstrates the effectiveness of the proposed CAT-LSTM. After analyzing patient representation learned by an auto-encoder, we identify 3 novel subphenotypes of AMD patients with different characteristics and progression rates to late AMD, paving the way for improved personalization of AMD management. The code of CAT-LSTM can be found at GitHub.
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PURPOSE: To determine the visual outcomes and effectiveness of glaucoma surgeries in congenital ectropion uvea. DESIGN: Retrospective interventional case series. METHODS: Surgeries and examination findings were collected on 11 eyes of 8 patients with congenital ectropion uvea at 2 academic sites from 2001 to 2021. Visual outcomes, surgical success (intraocular pressure [IOP]: 5-20 mm Hg, no additional IOP-lowering surgery, no visually devastating complications), and survival rates of glaucoma surgeries were assessed. RESULTS: Glaucoma in bilateral congenital ectropion uvea was diagnosed at an earlier age (0.02 ± 0.01 years) than unilateral disease (8.9 ± 5.3 years, P = .002). All eyes required glaucoma surgery with 91% requiring multiple surgeries (3.5 ± 2.1, median 3 surgeries per eye). Trabeculotomy (8 eyes) showed 13% success rate. Although none of the 4 eyes that underwent trabeculectomy with mitomycin C needed repeat trabeculectomy, glaucoma drainage device placement, or cycloablation, 75% required bleb revision surgery. Glaucoma drainage devices (7 eyes) had a 57% success rate with 3 eyes requiring subsequent cycloablation (2) or trabeculectomy (1). At the final follow-up (8.5 ± 6.6 years, median: 7.9 years), all eyes achieved IOP control, and IOP was lower compared with presentation (13.2 ± 2.6 mm Hg vs 32.9 ± 9.9 mm Hg, P = .002). Best-corrected logarithm of the minimum angle of resolution visual acuity at the final follow-up was 0.2 ± 0.2. CONCLUSIONS: Bilateral congenital ectropion uvea presents with glaucoma earlier than unilateral cases. The majority of eyes required multiple glaucoma surgeries. Angle surgery was less effective than trabeculectomy or glaucoma drainage devices. IOP control was obtained in all eyes and affected individuals had good visual outcomes.
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Ectrópio , Glaucoma , Trabeculectomia , Ectrópio/cirurgia , Seguimentos , Glaucoma/complicações , Glaucoma/congênito , Glaucoma/cirurgia , Humanos , Recém-Nascido , Pressão Intraocular , Estudos Retrospectivos , Resultado do Tratamento , ÚveaRESUMO
PURPOSE: The purpose of this study was to investigate the mechanism of potential droplet formation in response to air puff deformation with two noncontact tonometers (NCTs). METHODS: Twenty healthy volunteers were examined using two NCTs, Ocular Response Analyzer and Corvis ST, and two contact tonometers, iCare and Tono-Pen. High-speed videos of the tear film response were captured with at spatial resolution of 20 microns/pixel at 2400 fps. Droplet size, droplet velocity, distance between air puff impact location, and the tear meniscus-lid margin were characterized. RESULTS: One subject was excluded due to technical issues. Droplets were detected only in tests with instilled eye drop. Videos showed the tear film rolls away from the apex while remaining adherent to the ocular surface due to the tendency of the fluid to remain attached to a solid surface explained by the Coanda effect. Twelve out of 38 videos with an eye drop administration showed droplet formation. Only one resulted in droplets with predominantly forward motion, which had the shortest distance between air puff impact location and lower meniscus. This distance on average was 5.9 ± 1.1 mm. The average droplet size was 500 ± 200 µm. CONCLUSIONS: Results indicate no droplet formation under typical clinical setting. Hence, standard clinical use of NCT tests is not expected to cause droplets. NCT testing with eye drop administration showed droplet formation at the inferior eyelid boundary, which acts as a barrier and interrupts tear flow. TRANSLATIONAL RELEVANCE: Study of tear film interaction with NCT air puff shows that these tonometers are not expected to cause droplet formation in standard use and that if external drops are required, both eyelids should be held if patients need assistance to maintain open eyes to avoid droplets with predominantly forward motion.
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Hidrodinâmica , Lacerações , Humanos , Pressão Intraocular , Manometria , Soluções Oftálmicas , Tonometria OcularRESUMO
BACKGROUND: Singleton-Merten syndrome (SGMRT) is a rare immunogenetic disorder that variably features juvenile open-angle glaucoma (JOAG), psoriasiform skin rash, aortic calcifications and skeletal and dental dysplasia. Few families have been described and the genotypic and phenotypic spectrum is poorly defined, with variants in DDX58 (DExD/H-box helicase 58) being one of two identified causes, classified as SGMRT2. METHODS: Families underwent deep systemic phenotyping and exome sequencing. Functional characterisation with in vitro luciferase assays and in vivo interferon signature using bulk and single cell RNA sequencing was performed. RESULTS: We have identified a novel DDX58 variant c.1529A>T p.(Glu510Val) that segregates with disease in two families with SGMRT2. Patients in these families have widely variable phenotypic features and different ethnic background, with some being severely affected by systemic features and others solely with glaucoma. JOAG was present in all individuals affected with the syndrome. Furthermore, detailed evaluation of skin rash in one patient revealed sparse inflammatory infiltrates in a unique distribution. Functional analysis showed that the DDX58 variant is a dominant gain-of-function activator of interferon pathways in the absence of exogenous RNA ligands. Single cell RNA sequencing of patient lesional skin revealed a cellular activation of interferon-stimulated gene expression in keratinocytes and fibroblasts but not in neighbouring healthy skin. CONCLUSIONS: These results expand the genotypic spectrum of DDX58-associated disease, provide the first detailed description of ocular and dermatological phenotypes, expand our understanding of the molecular pathogenesis of this condition and provide a platform for testing response to therapy.
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Exantema , Glaucoma de Ângulo Aberto , Odontodisplasia , Proteína DEAD-box 58/genética , Exantema/patologia , Glaucoma de Ângulo Aberto/patologia , Humanos , Interferons/genética , Metacarpo/patologia , Odontodisplasia/genética , Odontodisplasia/patologia , Receptores ImunológicosRESUMO
A method motivated by the eye's aqueous veins is described for the imaging and strain calculation within soft biological tissues. A challenge to the investigation of the biomechanics of the aqueous vein-perilimbal sclera tissue complex is resolution of tissue deformations as a function of intraocular pressure and the subsequent calculation of strain (a normalized measure of deformation). The method involves perfusion of the eye with a contrast agent during conduction of non-invasive, optical resolution photoacoustic microscopy. This imaging technique permits three-dimensional displacement measurements of tracked points on the inner walls of the veins which are used in a finite element model to determine the corresponding strains. The methods are validated against two standard strain measurement methods. Representative porcine globe perfusion experiments are presented that demonstrate the power of the method to determine complex strain fields in the veins dependent on intraocular pressure as well as vein anatomy. In these cases, veins are observed to move radially outward during increases in intraocular pressure and to possess significant spatial strain variation, possibly influenced by their branching patterns. To the authors' knowledge, these are the only such quantitative, data driven, calculations of the aqueous vein strains available in the open literature.
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Imageamento Tridimensional/métodos , Técnicas Fotoacústicas/métodos , Esclera/fisiologia , Veias/fisiologia , Animais , Fenômenos Biomecânicos/fisiologia , Biofísica/métodos , Análise de Elementos Finitos , Pressão Intraocular/fisiologia , Disco Óptico/fisiologia , Estresse Mecânico , Suínos , Tonometria Ocular/métodosRESUMO
Purpose: To characterize the effects of timolol and latanoprost on calculated ocular perfusion pressure (OPP) in a multicenter, prospective, crossover-design study. Methods: Nonglaucomatous volunteers were evaluated at baseline, after 1 week of timolol 0.5% dosed twice daily, and after 1 week of latanoprost 0.005% dosed nightly (randomized treatment order; 6-week washout period). Pneumatonometric intraocular pressure (IOP) and brachial blood pressure (BP) were evaluated at each visit. Using 3 commonly used equations, OPP was calculated based on IOP and BP. The OPPs at each visit were compared by using linear mixed-effects models. Results: This analysis includes 121 participants (242 eyes; 75% female, 87% White, mean age 55 years). Mean OPP (standard deviation) calculated with mean arterial pressure was 46.8 (8.1) mmHg at baseline, 48.5 (7.9) mmHg with timolol (P = 0.005), and 49.6 mmHg (8.2) with latanoprost (P < 0.001). When compared with baseline, OPP calculated with diastolic BP was significantly increased with both timolol (1.3 mmHg) and latanoprost (3.1 mmHg). The OPP calculated with systolic BP was increased with latanoprost (2.8 mmHg) but decreased with timolol (-1.3 mmHg). Timolol reduced systolic BP by 3.2 mmHg. Compared with timolol, latanoprost conferred greater increases in OPP calculated with both systolic and diastolic BP compared with baseline; however, the difference in treatment effects on OPP calculated with mean arterial pressure was not significantly different (P = 0.068). Conclusion: In this crossover study of nonglaucomatous volunteers, latanoprost increased OPP. However, timolol's benefit to OPP may be limited in part because it reduced systolic BP. Clinical Trial Registration number: NCT01677507.
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Latanoprosta/farmacologia , Fenômenos Fisiológicos Oculares/efeitos dos fármacos , Soluções Oftálmicas/farmacologia , Timolol/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: Poor vision affects physical health but the relationship with depressive symptoms among midlife adults (40-65ây), who often present with early stage vision impairment (VI), is not well understood. The goal of this study was to assess the impact of vision on depressive symptoms during midlife. METHODS: The Michigan site of the Study of Women's Health Across the Nation conducted assessments of distance visual acuity at six consecutive, near-annual follow-up visits. At each visit, depressive symptoms (Center for Epidemiological Studies-Depression Scale) were assessed. VI was defined as mild (20/30-20/60) or moderate-severe (20/70 or worse). Multivariable logistic regression models using generalized estimating equations were used to assess the association of VI and reporting of depressive symptoms at the subsequent visit. RESULTS: At analytic baseline, the mean age of participants (Nâ=â226) was 50.0âyears (standard deviationâ=â2.6). More than half (53.5%) of women had mild VI and 8.0% had moderate-severe VI. Adjusting for age, preexisting depressive symptoms, race, education, economic strain, body mass index, and smoking, participants with mild and moderate-severe VI had 68% (95%âC (0.97-2.90)) and 2.55-fold (95% CI 1.13-5.75) higher odds of reporting depressive symptoms at their subsequent study visit as compared with women without VI. Further adjustment for diabetes, hypertension, and osteoarthritis attenuated the estimates and the associations were no longer statistically significant. CONCLUSION: VI was associated with increased odds of future depressive symptoms among mid-life women. Timely detection and appropriate correction of VI may be important to consider in maintaining the mental health status of midlife women.
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Depressão , Saúde da Mulher , Índice de Massa Corporal , Depressão/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Michigan/epidemiologia , Pessoa de Meia-IdadeRESUMO
Purpose: To assess ocular rigidity using dynamic optical coherence tomography (OCT) videos in glaucomatous and healthy subjects, and to evaluate how ocular rigidity correlates with biomechanical and morphological characteristics of the human eye. Methods: Ocular rigidity was calculated using Friedenwald's empirical equation which estimates the change in intraocular pressure (IOP) produced by volumetric changes of the eye due to choroidal pulsations with each heartbeat. High-speed OCT video was utilized to non-invasively measure changes in choroidal volume through time-series analysis. A control-case study design was based on 23 healthy controls and 6 glaucoma cases. Multiple diagnostic modalities were performed during the same visit including Spectralis OCT for nerve head video, Pascal Dynamic Contour Tonometry for IOP and ocular pulse amplitude (OPA) measurement, Corvis ST for measuring dynamic biomechanical response, and Pentacam for morphological characterization. Results: Combining glaucoma and healthy cohorts (n = 29), there were negative correlations between ocular rigidity and axial length (Pearson R = -0.53, p = 0.003), and between ocular rigidity and anterior chamber volume (R = -0.64, p = 0.0002). There was a stronger positive correlation of ocular rigidity and scleral stiffness (i.e., stiffness parameter at the highest concavity [SP-HC]) (R = 0.62, p = 0.0005) compared to ocular rigidity and corneal stiffness (i.e., stiffness parameter at the first applanation [SP-A1]) (R = 0.41, p = 0.033). In addition, there was a positive correlation between ocular rigidity and the static pressure-volume ratio (P/V ratio) (R = 0.72, p < 0.0001). Conclusions: Ocular rigidity was non-invasively assessed using OCT video and OPA in a clinic setting. The significant correlation of ocular rigidity with biomechanical parameters, SP-HC and P/V ratio, demonstrated the validity of the ocular rigidity measurement. Ocular rigidity is driven to a greater extent by scleral stiffness than corneal stiffness. These in vivo methods offer an important approach to investigate the role of ocular biomechanics in glaucoma.
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BACKGROUND: In older adults, vision impairment (VI) is associated with worse cognitive function. However, the relationship between midlife vision and future cognitive function remains unknown. METHODS: The Study of Women's Health Across the Nation, Michigan site, is a longitudinal cohort of midlife women aged 42-52 years at baseline. Presenting Titmus visual acuity (VA) in the better-seeing eye was assessed at baseline and categorized as no or mild VI (VA ≥20/60), or moderate or worse VI (VA <20/60). Cognitive function was measured 8 times over 15 years using the East Boston Memory Test immediate (EBMTi) and delayed (EBMTd) recall and the Digit Span Backwards (DSB) test. Linear mixed models with a random intercept and slope for age were constructed to detect associations between VI at baseline and future repeated measures of cognitive function, adjusting for age, race, education, financial strain, alcohol use, and tobacco use. RESULTS: About 394 women aged 42-52 at baseline with a maximum follow-up of 20 years were included in this analysis. After covariate adjustment, moderate or worse VI was associated with lower EMBTi (ß = -0.56, p = .012), EBMTd (ß = -0.60, p = .009), and DSB (ß = -0.84, p = .04). While we detected significant associations between VI and levels of cognitive function scores, rates of cognitive decline as individuals aged did not vary by VI status. CONCLUSION: Moderate or worse VI, assessed during midlife, was associated with lower scores on measures of cognitive function over a 15-year period during which women transitioned from midlife to older adulthood.
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Cognição , Disfunção Cognitiva , Transtornos da Visão/epidemiologia , Adulto , Idoso , Disfunção Cognitiva/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Michigan , Pessoa de Meia-Idade , Saúde da MulherRESUMO
PRECIS: The Michigan Screening and Intervention for Glaucoma and eye Health through Telemedicine (MI-SIGHT) program leverages community-engaged research, telemedicine, and health coaching to overcome key logistical and psychosocial barriers to improve glaucoma screening in underserved communities. PURPOSE: To describe the methodology of the implementation and evaluation of the MI-SIGHT Program. METHODS: The MI-SIGHT Program uses community engagement, telemedicine, and health coaching to overcome key logistical and psychosocial barriers to glaucoma identification and care among underserved populations. The MI-SIGHT Program will be evaluated in 2 community clinics: Hamilton Community Health Network, a federally qualified health center in Flint, Michigan, and the Hope Clinic, a free clinic in Ypsilanti, Michigan. A Community Advisory Board including the research team and health care providers, administrators, and patients from both clinics will guide program implementation. An ophthalmic technician at the community clinics will conduct screening tests for glaucoma and eye disease. The data will be transmitted through electronic health record to be reviewed by an ophthalmologist who will make recommendations for follow-up care. The ophthalmic technician will conduct a return visit to fit low-or no-cost glasses, help arrange follow-up with an ophthalmologist, and provide education. Those diagnosed with glaucoma or suspected glaucoma will be randomized to standard education or personalized glaucoma education and coaching. Costs will be assessed. RESULTS: The authors hypothesize that the MI-SIGHT Program will detect a higher prevalence rate of glaucoma than that found in the general population, improve upon presenting visual acuity, enhance vision-related quality of life, and demonstrate that personalized glaucoma education and coaching improve adherence to follow-up care. CONCLUSION: The MI-SIGHT Program may serve as a model for glaucoma screening and care in high-risk communities.
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Glaucoma , Telemedicina , Glaucoma/diagnóstico , Glaucoma/epidemiologia , Glaucoma/terapia , Humanos , Pressão Intraocular , Michigan/epidemiologia , Qualidade de VidaRESUMO
PURPOSE: Phentolamine mesylate ophthalmic solution (PMOS), applied to the eye topically, was shown previously to have beneficial effects in patients with dim light vision disturbances (DLD), including decreased pupil diameter (PD), improved best-corrected distance visual acuity (BCDVA), as well as lower intraocular pressure (IOP). The ORION-1 trial evaluated the long-term safety and efficacy of PMOS in a glaucomatous, presbyopic population. PATIENTS AND METHODS: In this randomized, double-masked, multi-center, placebo-controlled, multiple-dose Phase 2b trial, 39 patients with elevated IOP were randomized to receive one evening dose of study medication or placebo for 14 days. The primary outcome measure was mean change in diurnal IOP, and the key secondary outcome measures included changes in PD, distance-corrected near visual acuity (DCNVA), and conjunctival hyperemia. RESULTS: Use of 1% PMOS did not lead to a statistically significant decrease in diurnal IOP compared to placebo (P = 0.89) but trended toward a greater decrease in patients with lower IOP baselines. PMOS produced a statistically significant mean 20% PD reduction under both photopic and mesopic conditions that was sustained for 36 hours post-dosing. A statistically significant number of patients with PMOS compared to placebo demonstrated ≥1 line of improvement in photopic DCNVA at day 8 (P = 0.0018), day 15 (P = 0.0072), and day 16 (P = 0.0163), with a trend for 2- and 3-line improvements at all time points. There was no statistical difference in conjunctival hyperemia compared to placebo. CONCLUSION: Although mean IOP was not lowered significantly, daily evening dosing of 1% PMOS was found to be well tolerated with no daytime conjunctival redness and demonstrated improvement in DCNVA with sustained PD reduction in a glaucomatous and presbyopic population. Smaller pupil size can have beneficial effects in improving symptoms of presbyopia and DLD, which will be the focus of further studies.
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PRCIS: Community-engaged research (CER) enables researchers to identify community-specific barriers and facilitators to program implementation. Broadly applicable barriers to glaucoma care, such as Cost, Transportation, and Trust, and community-specific barriers, such as Language and Convenience/Access, were identified. PURPOSE: The aim was to identify the facilitators and barriers to implementing glaucoma screening programs in 2 community clinics. METHODS: A concurrent mixed-methods process analysis using CER. Key stakeholders-including patients, providers, and staff members-from 2 community clinics were interviewed using a semistructured interview guide. Interviews had 2 parts: (1) asking patients about community-based facilitators and barriers to implementing glaucoma screening and care and (2) eliciting feedback about a personalized coaching program. The transcripts were coded using Grounded Theory. Number of participants and number of representative citations were counted per theme. The qualitative analysis was coded using Dedoose 8.3.17 (Los Angeles, CA). RESULTS: Thematic saturation was reached after coding 12 interviews. 30 participants were interviewed, 13 from Hamilton Clinic (Flint, MI; 8 patients, 5 providers and staff members) and 17 from Hope Clinic (Ypsilanti, MI; 6 patients, 11 providers and staff members). The most commonly cited themes were: Priorities (98 citations, 30 participants), Knowledge (73, 26) Transportation (63, 26), Cost (60, 23), and Convenience/Access (63, 22). Broadly applicable barriers to glaucoma care, such as Cost, Transportation, and Trust were identified alongside community-specific barriers such as Language and Convenience/Access. Participants rated their likelihood to follow up with an ophthalmologist after participating in the personalized coaching program at a mean of 8.83 (on a scale of 1 to 10 with 10 being the most confident). CONCLUSIONS: CER enables researchers to identify community-specific barriers and facilitators, allowing more effective program implementation.
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Glaucoma , Pressão Intraocular , Instituições de Assistência Ambulatorial , Glaucoma/diagnóstico , Humanos , Programas de RastreamentoRESUMO
Nanophthalmos is a rare condition defined by a small, structurally normal eye with resultant high hyperopia. While six genes have been implicated in this hereditary condition (MFRP, PRSS56, MYRF, TMEM98, CRB1,VMD2/BEST1), the relative contribution of these to nanophthalmos or to less severe high hyperopia (≥ + 5.50 spherical equivalent) has not been fully elucidated. We collected probands and families (n = 56) with high hyperopia or nanophthalmos (≤ 21.0 mm axial length). Of 53 families that passed quality control, plausible genetic diagnoses were identified in 10/53 (18.8%) by high-throughput panel or pooled exome sequencing. These include 1 TMEM98 family (1.9%), 5 MFRP families (9.4%), and 4 PRSS56 families (7.5%), with 4 additional families having single allelic hits in MFRP or PRSS56 (7.5%). A novel deleterious TMEM98 variant (NM_015544.3, c.602G>C, p.(Arg201Pro)) segregated with disease in 4 affected members of a family. Multiple novel missense and frameshift variants in MFRP and PRSS56 were identified. PRSS56 families were more likely to have choroidal folds than other solved families, while MFRP families were more likely to have retinal degeneration. Together, this study defines the prevalence of nanophthalmos gene variants in high hyperopia and nanophthalmos and indicates that a large fraction of cases remain outside of single gene coding sequences.
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Oftalmopatias Hereditárias/genética , Mutação da Fase de Leitura/genética , Hiperopia/genética , Proteínas de Membrana/genética , Microftalmia/genética , Mutação de Sentido Incorreto/genética , Serina Proteases/genética , Alelos , Estudos de Coortes , Olho/metabolismo , Feminino , Humanos , Masculino , Linhagem , Estados UnidosRESUMO
PURPOSE: The purpose of this study was to evaluate the ability to screen for glaucoma using a Food Drug Administration (FDA) Class II diagnostic digital fundus photography system used for diabetic retinopathy screening (DRS). METHODS: All research participants underwent a comprehensive eye examination as well as non-mydriatic 45°single photograph retinal imaging centered on the macula. Optic nerve images within the 45° non-mydriatic and non-stereo DRS image were evaluated by two methods: 1) grading by three glaucoma specialists, and 2) a computer-aided automated segmentation system to determine the vertical cup-to-disc ratio (VCDR). Using VCDR from clinical assessment as gold standard, VCDR results from two methods were compared to that from clinical assessment. Inter-grader agreement was assessed by computing intraclass correlation coefficient (ICC). In addition, sensitivity and specificity were calculated. RESULTS: Among 245 fundus photos, 166 images met quality specifications for analysis. Fifty images were not processed by the automated system due to the poor quality of the optic disc, and 29 images did not include the optic nerve head due to the patient movement during the photo acquisition. The ICC value for the VCDR between the gold standard clinical exam and the automated system was 0.41, indicating fair agreement. The ICC value between the three ophthalmologists and the gold standard was 0.51, 0.56, and 0.69, respectively, indicating fair to moderate agreement. DISCUSSION: Assessing the VCDR on non-mydriatic and non-stereo DRS fundus photographs by either the computer-aided automated segmentation system or by glaucoma specialists showed similar fair to moderate agreement. In summary, optic nerve assessment for glaucoma from these 45° non-mydriatic and non-stereo DRS images is not yet suitable for tele-glaucoma screening.
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PURPOSE: Ultrasound biomicroscopy (UBM) has been used to characterize anterior segment dimensions in plateau iris configuration (PIC), but transverse measurements between the recesses of the ciliary sulcus (sulcus-to-sulcus diameter [STSD]) and the ciliary body processes (interplicata diameter [IPD]) have not been reported. We measured STSD and IPD and compared these among eyes with PIC, primary angle closure (PAC), and control eyes with open angles. DESIGN: Retrospective, cross-sectional clinical study. PARTICIPANTS: Sixty-nine participants, 37 PIC, 13 PAC, and 19 controls. METHODS: We searched our clinical UBM database for PAC and PIC cases. Controls were assembled by reviewing images obtained for surveillance of ocular surface lesions. Anterior segment measurements were performed using the UBM digital caliper tool. Robust-fit ANOVA identified among-group differences. Pairwise t tests were used to test the significance of between-group differences. MAIN OUTCOME MEASURES: Anterior chamber depth (ACD), angle opening distance (AOD), ciliary body area and thickness, iris area, horizontal and vertical STSD, and horizontal and vertical IPD. RESULTS: Fifty-five left eyes were analyzed (30 PIC, 10 PAC, and 15 controls). ACD was smaller in PAC than in PIC and control eyes (P < 0.05 for PIC vs. PAC; P < 0.01 for control vs. PAC). Mean AOD was smaller in PIC than controls (P < 0.05) and smaller in PAC than PIC (P < 0.001). Vertical STSD was smaller in both PAC and PIC than controls (P = 0.04 for PIC vs. control; P < 0.01 for PAC vs. control). Horizontal STSD was smaller in PIC than controls (P = 0.02). Vertical IPD was smaller in PIC than controls (P = 0.04) and smaller in PAC than PIC eyes (P = 0.02). Horizontal IPD was smaller in PIC and PAC than controls (P = 0.03 for PIC vs. control; P < 0.01 for PAC vs. control). CONCLUSIONS: STSD and IPD are narrower in PIC and PAC than in healthy eyes. Further studies that examine the ratio of white-to-white cornea diameter to the IPD may provide a mechanism for reported cases of in-the-bag uveitis-glaucoma-hyphema syndrome in PIC.
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Câmara Anterior/diagnóstico por imagem , Pressão Intraocular/fisiologia , Doenças da Íris/diagnóstico , Corpo Ciliar/diagnóstico por imagem , Estudos Transversais , Gerenciamento de Dados , Feminino , Seguimentos , Gonioscopia , Humanos , Masculino , Microscopia Acústica , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: The surgical management of glaucoma associated with Axenfeld-Rieger Syndrome (ARS) is poorly described in the literature. The goal of this study is to compare the effectiveness of various glaucoma surgeries on intraocular pressure (IOP) management in ARS. METHODS: Retrospective cohort study at a university hospital-based practice of patients diagnosed with ARS between 1973 and 2018. Exclusion criterion was follow-up less than 1 year. The number of eyes with glaucoma (IOP ≥ 21 mmHg with corneal edema, Haabs striae, optic nerve cupping or buphthalmos) requiring surgery was determined. The success and survival rates of goniotomy, trabeculotomy±trabeculectomy (no antifibrotics), cycloablation, trabeculectomy with anti-fibrotics, and glaucoma drainage device placement were assessed. Success was defined as IOP of 5-20 mmHg and no additional IOP-lowering surgery or visually devastating complications. Kaplan-Meier survival curves and the Wilcoxon test were used for statistical analysis. RESULTS: In 32 patients identified with ARS (median age at presentation 6.9 years, 0-58.7 years; median follow-up 5.4 years, 1.1-43.7 years), 23 (71.9%) patients were diagnosed with glaucoma at median age 6.3 years (0-57.9 years). In glaucomatous eyes (46 eyes), mean IOP at presentation was 21.8 ± 9.3 mmHg (median 20 mmHg, 4-45 mmHg) on 1.0 ± 1.6 glaucoma medications. Thirty-one eyes of 18 patients required glaucoma surgery with 2.2 ± 1.2 IOP-lowering surgeries per eye. Goniotomy (6 eyes) showed 43% success with 4.3 ± 3.9 years of IOP control. Trabeculotomy±trabeculectomy (6 eyes) had 17% success rate with 14.8 ± 12.7 years of IOP control. Trabeculectomy with anti-fibrotics (14 eyes) showed 57% success with 16.5 ± 13.5 years of IOP control. Ahmed© (FP7 or FP8) valve placement (8 eyes) had 25% success rate with 1.7 ± 1.9 years of IOP control. Baerveldt© (250 or 350) device placement (8 eyes) showed 70% success with 1.9 ± 2.3 years of IOP control. Cycloablation (4 eyes) had 33% success rate with 2.7 ± 3.5 years of IOP control. At final follow-up, mean IOP (12.6 ± 3.8 mmHg, median 11.8 mmHg, 7-19 mmHg) in glaucomatous eyes was significantly decreased (p < 0.0001), but there was no difference in number of glaucoma medications (1.6 ± 1.5, p = 0.1). CONCLUSIONS: In our series, greater than 70% of patients with ARS have secondary glaucoma that often requires multiple surgeries. Trabeculectomy with anti-fibrotics and Baerveldt glaucoma drainage devices showed the greatest success in obtaining IOP control.
Assuntos
Segmento Anterior do Olho/anormalidades , Anormalidades do Olho/complicações , Oftalmopatias Hereditárias/complicações , Glaucoma/cirurgia , Adolescente , Adulto , Segmento Anterior do Olho/fisiopatologia , Criança , Pré-Escolar , Criocirurgia , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/fisiopatologia , Oftalmopatias Hereditárias/diagnóstico , Oftalmopatias Hereditárias/fisiopatologia , Feminino , Seguimentos , Glaucoma/etiologia , Glaucoma/fisiopatologia , Implantes para Drenagem de Glaucoma , Humanos , Lactente , Recém-Nascido , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tonometria Ocular , Trabeculectomia , Acuidade VisualRESUMO
PURPOSE: To conduct a qualitative description of corneal and glaucoma outcomes in Peters anomaly. DESIGN: Retrospective case series. METHODS: Children with Peters anomaly who presented between 1982-2017 were included. Visual acuity, intraocular pressure (IOP), survival of corneal grafts, and success of glaucoma surgery (defined as IOP of 5-20 mm Hg and no additional IOP-lowering surgery or visually devastating complications) were analyzed. RESULTS: Fifty-eight eyes of 37 patients (19 males) with Peters anomaly presented at 0.7 ± 1.5 years of age and had a follow-up of 10.2 ± 10.8 years. Twenty-three eyes underwent penetrating keratoplasty (PKP) with an average of 2.0 ± 1.3 grafts per eye. PKP survival at 1 year was 60% (95% confidence interval 41-75%) but decreased at 10 years to 34% (95% confidence interval 18-51%). Thirty-four eyes were diagnosed with glaucoma at 2.8 ± 6.4 years of age. Twenty eyes required glaucoma surgery, and the average number of IOP-lowering surgeries was 2.9 ± 2.0 per eye. Glaucoma drainage devices (15 eyes) had a 53% success rate. Laser cycloablation (9 eyes, transcleral or endoscopic) had a success rate of 67% with 2.0 ± 1.0 treatments per eye. Trabeculectomy with mitomycin C (8 eyes) and trabeculotomy (8 eyes) had 25% and 0% success rates, respectively. Fifteen eyes that underwent glaucoma surgery obtained IOP control, and GDD with or without cycloablation accounted for 80% of the successes. Eyes that underwent PKP did not show increased rates of glaucoma, higher IOP, or a greater necessity for IOP-lowering surgery. CONCLUSIONS: In Peters anomaly, PKP shows poor long-term success. In addition, >50% of eyes with Peters anomaly have secondary glaucoma that often requires multiple surgeries.