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JAMA Ophthalmology Jun 2024Intraocular pressure (IOP) elevations of clinical relevance have been observed after the commonly used 0.05-mL volume for intravitreous injections. However, more...
IMPORTANCE
Intraocular pressure (IOP) elevations of clinical relevance have been observed after the commonly used 0.05-mL volume for intravitreous injections. However, more recently approved intravitreous agents involve volumes from 0.07 to 0.1 mL. It is not well established whether repeated 0.1-mL intravitreous injections may result in IOP-related complications.
OBJECTIVE
To investigate the effect of 1 year of repeated 0.1-mL intravitreous injections on IOP outcomes.
DESIGN, SETTING, AND PARTICIPANTS
This study was a post hoc analysis of 2 clinical trials investigating the IOP safety of intravitreous lampalizumab on geographic atrophy secondary to age-related macular degeneration. Both trials were conducted between 2014 and 2018 and recruited participants who were 50 years or older and had bilateral geographic atrophy. This post hoc analysis was performed between 2018 and 2022.
INTERVENTIONS
Intravitreous lampalizumab, 0.1 mL, every 4 weeks; lampalizumab, 0.1 mL, every 6 weeks; or sham procedure every 4 weeks or 6 weeks for 48 weeks.
MAIN OUTCOMES AND MEASURES
IOP changes in the 4-week-frequency study arms and ocular adverse events to week 48 in all arms. The hypothesis for this analysis was formulated after data collection.
RESULTS
Among a total of 1851 participants, there was no change in mean pre-injection IOP values through 48 weeks in either arm. The adverse events glaucoma and ocular hypertension were reported for 1.8% of participants treated with lampalizumab and 1.6% of those in the sham arm.
CONCLUSIONS AND RELEVANCE
Over 1 year, IOP increases were rare and did not affect treated participants more frequently than sham arm participants. These findings support the low risk of persistent IOP increases, on average, of intravitreous 0.1-mL injection volumes administered for 1 year in a manner similar to that performed in these clinical trials. These results may be valuable in the design of future therapeutic trials considering this volume for injections particularly as more recently approved agents use volumes of 0.07 to 0.1 mL.
TRIAL REGISTRATION
ClinicalTrials.gov Identifiers: NCT02247479 and NCT02247531.
PubMed: 38900484
DOI: 10.1001/jamaophthalmol.2024.2061 -
Translational Vision Science &... Jun 2024The VisuALL S is an automated, static threshold, virtual reality-based perimeter for mobile evaluation of the visual field. We examined same-day and 3-month...
PURPOSE
The VisuALL S is an automated, static threshold, virtual reality-based perimeter for mobile evaluation of the visual field. We examined same-day and 3-month repeatability.
METHODS
Adult participants with a diagnosis of glaucoma or ocular hypertension underwent two VisuALL 24-2 Normal T- Full threshold strategy tests at baseline and one additional exam at 3 months for each eligible eye. Spearman, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to assess the correlation of individual point sensitivities and mean deviation (MD) among three tests.
RESULTS
Eighty-eight eyes (44 participants) were included. Average age was 68.1 ± 14.3 years, and 60.7% were male. VisuALL MD was highly correlated between tests (intravisit: r = 0.89, intervisit: r = 0.82; P < 0.001 for both). Bland-Altman analysis showed an average difference in intravisit MD of -0.67 dB (95% confidence interval [CI], -6.04 to 4.71 dB) and -0.15 dB (95% CI, -8.04 to 7.73 dB) for intervisit exams. Eight-five percent of pointwise intravisit ICCs were above 0.75 (range, 0.63 to 0.93), and 65% of pointwise intervisit ICCs were above 0.75 (range, 0.55 to 0.91).
CONCLUSIONS
VisuALL demonstrated high correlation of MD between tests and good repeatability for individual point sensitivities among three tests in 3 months, except at the points around the blind spot and superiorly.
TRANSLATIONAL RELEVANCE
The preliminary reproducibility results for VisuALL are encouraging. Its portable design makes it a potentially useful tool for patients with glaucoma, enabling more frequent assessments both at home and in clinical settings.
Topics: Humans; Male; Ocular Hypertension; Female; Aged; Reproducibility of Results; Middle Aged; Virtual Reality; Visual Field Tests; Glaucoma; Visual Fields; Aged, 80 and over; Intraocular Pressure; Prospective Studies
PubMed: 38899952
DOI: 10.1167/tvst.13.6.14 -
Neurosurgery Jun 2024Aneurysms in the cavernous segment of the internal carotid artery (ICA) often present in an indolent fashion with limited morbidity. However, their growth progression...
BACKGROUND AND OBJECTIVES
Aneurysms in the cavernous segment of the internal carotid artery (ICA) often present in an indolent fashion with limited morbidity. However, their growth progression and possible rupture over time remains poorly defined, thereby limiting optimization of serial follow-up. Thus, we aim to describe the progression of cavernous ICA aneurysms over time, as well as the patient and aneurysm characteristics associated with possible growth and rupture status.
METHODS
We identified a consecutive cohort of 157 patients from 2007 to 2021 with cavernous ICA aneurysms. Patient demographic data, possible risk factors, presenting symptoms, radiographic features of aneurysms, size progression, rupture status, and concomitant noncavernous aneurysm rupture data were manually extracted.
RESULTS
One hundred and fifty-seven patients (mean age at diagnosis 57.2 ± 15.6 years; 85.4% females) with 174 cavernous carotid aneurysms (CCAs) were followed for an average of 7.1 ± 4.8 years. 76.4% of aneurysms were identified incidentally, with predominantly ocular palsies as the presenting symptoms in remaining primary cases. Most aneurysms were small, and of the 168 aneurysms that were followed, 98.2% did not demonstrate appreciable growth. Of the aneurysms that grew, it took an average of 6.0 years to grow 1.6 ± 0.2 mm. Demographic data, hypertension, and smoking status were not associated with aneurysm growth. Most radiographic features also were not associated with growth, except long-axis diameter, which had an odds ratio of 1.4 (CI: 1.2, 1.8) on multivariable analysis. Presenting clinical symptoms were not associated with growth. No CCAs ruptured during follow-up.
CONCLUSION
Cavernous ICA aneurysms in our series demonstrate no rupture and limited growth over years of clinical follow-up. No radiographic or patient risk factors were associated with growth except initial aneurysm size. Hence, small CCAs may not require close follow-up over time.
PubMed: 38899866
DOI: 10.1227/neu.0000000000003033 -
Drug Delivery Dec 2024Glaucoma is the leading cause of blindness worldwide. However, its surgical treatment, in particular via trabeculectomy, can be complicated by fibrosis. In current...
Glaucoma is the leading cause of blindness worldwide. However, its surgical treatment, in particular via trabeculectomy, can be complicated by fibrosis. In current clinical practice, application of the drug, Mitomycin C, prevents or delays fibrosis, but can lead to additional side effects, such as bleb leakage and hypotony. Previous drug screening and testing has identified the known antibiotic, josamycin, as a possible alternative antifibrotic medication with potentially fewer side effects. However, a suitable ocular delivery mechanism for the hydrophobic drug to the surgical site does not yet exist. Therefore, the focus of this paper is the development of an implantable drug delivery system for sustained delivery of josamycin after glaucoma surgery based on crosslinked γ-cyclodextrin. γ-Cyclodextrin is a commonly used solubilizer which was shown to complex with josamycin, drastically increasing the drug's solubility in aqueous solutions. A simple γ-cyclodextrin crosslinking method produced biocompatible hydrogels well-suited for implantation. The crosslinked γ - cyclodextrin retained the ability to form complexes with josamycin, resulting in a 4-fold higher drug loading efficiency when compared to linear dextran hydrogels, and prolonged drug release over 4 days.
Topics: Hydrogels; Delayed-Action Preparations; gamma-Cyclodextrins; Solubility; Drug Liberation; Drug Delivery Systems; Glaucoma; Anti-Bacterial Agents; Drug Carriers; Animals; Humans; Cross-Linking Reagents
PubMed: 38899440
DOI: 10.1080/10717544.2024.2361168 -
Experimental Cell Research Jul 2024Glaucoma is characterized by pathological elevation of intraocular pressure (IOP) due to dysfunctional trabecular meshwork (TM), which is the primary cause of...
Glaucoma is characterized by pathological elevation of intraocular pressure (IOP) due to dysfunctional trabecular meshwork (TM), which is the primary cause of irreversible vision loss. There are currently no effective treatment strategies for glaucoma. Mitochondrial function plays a crucial role in regulating IOP within the TM. In this study, primary TM cells treated with dexamethasone were used to simulate glaucomatous changes, showing abnormal cellular cytoskeleton, increased expression of extracellular matrix, and disrupted mitochondrial fusion and fission dynamics. Furthermore, glaucomatous TM cell line GTM3 exhibited impaired mitochondrial membrane potential and phagocytic function, accompanied by decreased oxidative respiratory levels as compared to normal TM cells iHTM. Mechanistically, lower NAD + levels in GTM3, possibly associated with increased expression of key enzymes CD38 and PARP1 related to NAD + consumption, were observed. Supplementation of NAD + restored mitochondrial function and cellular viability in GTM3 cells. Therefore, we propose that the aberrant mitochondrial function in glaucomatous TM cells may be attributed to increased NAD + consumption dependent on CD38 and PARP1, and NAD + supplementation could effectively ameliorate mitochondrial function and improve TM function, providing a novel alternative approach for glaucoma treatment.
Topics: Trabecular Meshwork; Mitochondria; Glaucoma; NAD; Humans; Membrane Potential, Mitochondrial; Intraocular Pressure; Cell Survival; ADP-ribosyl Cyclase 1; Cell Line; Poly (ADP-Ribose) Polymerase-1; Dexamethasone; Cells, Cultured
PubMed: 38897410
DOI: 10.1016/j.yexcr.2024.114137 -
Applied Clinical Informatics May 2024In times of omnipresent digitization and big data, telemedicine and electronic case files (ECFs) are gaining ground for networking between players in the health care...
BACKGROUND
In times of omnipresent digitization and big data, telemedicine and electronic case files (ECFs) are gaining ground for networking between players in the health care sector. In the context of the SALUS study, this approach is applied in practice in the form of electronic platforms to display and process disease-relevant data of glaucoma patients.
OBJECTIVES
The SALUS ECF is designed and implemented to support data acquisition and presentation, monitoring, and outcome control for patients suffering from glaucoma in a clinical setting. Its main aim is to provide a means for out- and inpatient exchange of information between various stakeholders with an intuitive user interface in ophthalmologic care. Instrument data, anamnestic data, and diagnostic assessments need to be accessible and historic data stored for patient monitoring. Quality control of the data is ensured by a reading center.
METHODS
Based on an intensive requirement analysis, we implemented the ECF as a web-based application in React with a Datomic back-end exposing REST and GraphQL APIs for data access and import. A flexible role management was developed, which addresses the various tasks of multiple stakeholders in the SALUS study. Data security is ensured by a comprehensive encryption concept. We evaluated the usability and efficiency of the ECF by measuring the durations medical doctors need to enter and work with the data.
RESULTS
The evaluation showed that the ECF is time-saving in comparison to paper-based assessments and offers supportive monitoring and outcome control for numerical and imaging-related data. By allowing patients and physicians to access the digital ECF, data connectivity as well as patient autonomy were enhanced.
CONCLUSION
ECFs have a great potential to efficiently support all patients and stakeholders involved in the care of glaucoma patients. They benefit from the efficient management and view of the data tailored to their specific role.
Topics: Glaucoma; Humans; Tonometry, Ocular; Self Care; Telemedicine; Electronic Health Records
PubMed: 38897231
DOI: 10.1055/s-0044-1787008 -
International Ophthalmology Jun 2024As the epidemiological and burden trends of glaucoma are changing, it is extremely necessary to re-investigate geographical differences and trends. Here we use data from...
PURPOSE
As the epidemiological and burden trends of glaucoma are changing, it is extremely necessary to re-investigate geographical differences and trends. Here we use data from the 2019 Global burden of Disease, which aims to report the prevalence and disability-adjusted life years of glaucoma injury to assess the latest epidemiological models and trends from 1990 to 2019.
METHOD
Annual case numbers, age-standardized rates of prevalence, DALYs, and their estimated annual percentage changes (EAPCs) for glaucoma between 1990 and 2019 were derived from the GBD 2019 study. The relationship between glaucoma disease burden and social demographic index (SDI) was also investigated in this study.
RESULTS
In 2019, there were 7.47 million prevalent cases and 0.75 million DALYs cases, which increased by 92.53% and 69.23% compared with 1990 respectively. The global age-standardized rate of prevalence (ASPR) and age-standardized rate of DALYs (ASDR) decreased during 1990-2019 (EAPC = - 0.55 and - 1, respectively). In 2019, the highest ASPR and ASDR of Glaucoma were all observed in Mali, whereas the lowest occurred in Taiwan (Province of China). In terms of gender, males were more likely to suffer from glaucoma than females, especially the elderly.
CONCLUSIONS
The global prevalence and DALYs of glaucoma had an absolute increase during the past 30 years. The disease burden caused by glaucoma is closely related to socioeconomic level, age, gender, and other factors, and these findings provide a basis for policymakers from the perspective of social management.
Topics: Humans; Global Burden of Disease; Glaucoma; Prevalence; Female; Male; Middle Aged; Aged; Adult; Global Health; Age Distribution; Disability-Adjusted Life Years; Sex Distribution; Quality-Adjusted Life Years; Adolescent; Aged, 80 and over; Young Adult; Child; Cost of Illness; Blindness
PubMed: 38896279
DOI: 10.1007/s10792-024-03222-6 -
F1000Research 2023The purpose of this study was to compare iCare HOME (TA022) with Goldmann applanation tonometer and to evaluate the self-tonometry measurements among the Indian...
The purpose of this study was to compare iCare HOME (TA022) with Goldmann applanation tonometer and to evaluate the self-tonometry measurements among the Indian population. Eligible patients underwent iCare HOME training through guided demonstration (verbal, pictorial, video) and practised self-tonometry measures using iCare HOME. Certification for independent iCare HOME measure was provided if first iCare HOME intraocular pressure (IOP) measurement fell within ± 5 mmHg of Goldmann applanation tonometer (GAT) measurement which was measured by the trained clinician (principal investigator). Certified participants underwent simulated home self-tonometry measurements using iCare HOME, and agreement with GAT IOP measurements was assessed. Seven of 83 participants (8.43%) failed to complete the study due to difficulty in performing the task, leading to non-certification. Patients who could use the iCare HOME had a mean age of 53 ± 15.55years (53% males; 46% females). Only one in 12 subjects did not qualify to use iCare HOME. The overall mean difference between iCare HOME and GAT was 0.83 mmHg (95%, 3.92 and -2.25). At various pressure ranges, 7-16 mmHg, 17-23 mmHg and >23 mmHg, the mean difference between iCare HOME and GAT was 1.22 mmHg (95%, 4.32 and -1.86), 0.77 mmHg (95%,3.69 and -2.19), -0.11 mmHg (95%, 2.52 and -2.74) respectively. The intra-class correlation coefficient of the iCare HOME device was 0.997(95% CI,0.995-0.998). Patients were able to perform self- tonometry using iCare HOME with good reliability and safety. iCare HOME can be used to address the issue of difficulty in acquiring frequent and diurnal IOP measurements by patients doing self-tonometry from home.
Topics: Humans; Male; Intraocular Pressure; Female; Glaucoma; Tonometry, Ocular; Middle Aged; Adult; Aged; Self Care
PubMed: 38894819
DOI: 10.12688/f1000research.123104.2 -
International Journal of Molecular... Jun 2024Although glaucoma is a leading cause of irreversible blindness worldwide, its pathogenesis is incompletely understood, and intraocular pressure (IOP) is the only...
Although glaucoma is a leading cause of irreversible blindness worldwide, its pathogenesis is incompletely understood, and intraocular pressure (IOP) is the only modifiable risk factor to target the disease. Several associations between the gut microbiome and glaucoma, including the IOP, have been suggested. There is growing evidence that interactions between microbes on the ocular surface, termed the ocular surface microbiome (OSM), and tear proteins, collectively called the tear proteome, may also play a role in ocular diseases such as glaucoma. This study aimed to find characteristic features of the OSM and tear proteins in patients with glaucoma. The whole-metagenome shotgun sequencing of 32 conjunctival swabs identified Actinobacteria, Firmicutes, and Proteobacteria as the dominant phyla in the cohort. The species was only found in healthy controls, and their conjunctival microbiomes may be enriched in genes of the phospholipase pathway compared to glaucoma patients. Despite these minor differences in the OSM, patients showed an enrichment of many tear proteins associated with the immune system compared to controls. In contrast to the OSM, this emphasizes the role of the proteome, with a potential involvement of immunological processes in glaucoma. These findings may contribute to the design of new therapeutic approaches targeting glaucoma and other associated diseases.
Topics: Humans; Glaucoma; Proteome; Male; Female; Microbiota; Tears; Middle Aged; Eye Proteins; Aged; Conjunctiva; Metagenome; Adult
PubMed: 38892444
DOI: 10.3390/ijms25116257 -
International Journal of Molecular... May 2024To analyze in vivo scleral changes induced by MicroPulse transscleral laser therapy (MP-TLT) in refractory glaucoma using anterior segment-optical coherence tomography...
To analyze in vivo scleral changes induced by MicroPulse transscleral laser therapy (MP-TLT) in refractory glaucoma using anterior segment-optical coherence tomography (AS-OCT). Forty-two candidate patients for MP-TLT were consecutively enrolled and underwent AS-OCT at baseline and after six months. MP-TLT success was defined as an intraocular pressure (IOP) reduction by one-third. The main outcome measures were the mean superior (S-), inferior (I-), and total (T-) intra-scleral hypo-reflective space area (MISHA: mm) and scleral reflectivity (S-SR, I-SR, T-SR; arbitrary scale) as in vivo biomarkers of uveoscleral aqueous humor (AH) outflow. The IOP was the secondary outcome. The relations between the baseline-to-six months differences (D) of DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, DT-SR, and DIOP, were investigated. At 6 months, the median IOP reduction was 21% in the failures and 38% in the successes. The baseline S-MISHA, I-MISHA, and T-MISHA did not differ between the groups, while S-SR and T-SR were higher in the successes ( < 0.05). At six months, successful and failed MP-TLTs showed a 50% increase in S-MISHA ( < 0.001; = 0.037), whereas I-SR and T-SR reduced only in the successes ( = 0.002; = 0.001). When comparing DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, and DT-SR, there were no significant differences between the groups. In the successful procedures, DIOP was positively correlated with DT-MISHA and DI-MISHA (ρ = 0.438 and ρ = 0.490; < 0.05). MP-TLT produced potentially advantageous modifications of the sclera in refractory glaucoma. Given the partial correlation between these modifications and post-treatment IOP reduction, our study confirmed that the activation of the uveoscleral AH outflow route could significantly contribute to the IOP lowering after MP-TLT.
Topics: Humans; Tomography, Optical Coherence; Sclera; Male; Female; Glaucoma; Middle Aged; Intraocular Pressure; Laser Therapy; Aged; Aqueous Humor; Uvea; Adult; Treatment Outcome
PubMed: 38892100
DOI: 10.3390/ijms25115913