[Effects of oral bupranolol on aqueous dynamics in primary open-angle glaucoma (a preliminary report) (author's transl)].
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Numerous compelling observational studies have indicated that migraine is a risk factor for the development of glaucoma. Nevertheless, some studies have observed entirely opposite results. The objective of our research is to evaluate the potential relationship between migraine and glaucoma by employing a bidirectional Mendelian Randomization (MR) approach. This method enables us to rigorously assess the causal links between these 2 conditions, thereby addressing the discrepancies in existing literature. Independent genetic variants associated with glaucoma and migraine at the genome-wide significance level were selected as instrumental variables. All summary data were obtained from the genome-wide association study database. The primary method employed in the bidirectional MR analysis was the inverse variance weighted method, while sensitivity analyses utilized the leave-one-out method, MR-Egger method, and MR-Pleiotropy RESidual Sum and Outlier‌ method. When migraine and its subtypes (specifically migraine with aura and migraine without aura) were evaluated as exposure factors, we found no evidence of a causal relationship with glaucoma and its subtypes (namely angle-closure glaucoma and open-angle glaucoma). Subsequently, in the reverse MR analysis, when glaucoma and its subtypes (angle-closure glaucoma and open-angle glaucoma) were assessed as exposure factors, there was no substantial evidence to support a causal relationship with migraine or its subtypes (migraine with aura and migraine without aura). Furthermore, sensitivity analyses also reinforced the robustness of our bidirectional MR findings. Our bidirectional MR analysis mitigates the biases associated with traditional observational studies, highlighting that there is no direct causal relationship between migraine and the risk of glaucoma.
Eleven subjects with normal eyes and sixteen subjects with open-angle glaucoma had a selective alpha-adrenergic blocking agent, thymoxamine hydrochloride 0.5 per cent eyedrop, applied to one of their eyes. This consistently produced miosis, but did not significantly alter the intraocular pressure or the tonographically determined facility of aqueous outflow. Because we find that thymoxamine can selectively induce miosis without significant accompanying effect on the ciliary muscle or facility of outflow, we expect that this drug may prove to be a useful diagnostic adjunct to gonioscopy in distinguishing between angle-closure glaucoma and open-angle glaucoma with narrow angle. It seems worthwhile proceeding with clinical evaluation of this possibility.
IMPORTANCE: Elevated intraocular pressure (IOP) is a risk factor for primary open-angle glaucoma, and genetic risk scores hold promise as a tool for screening for ocular hypertension. However, genetic risk scores for IOP have a nonuniform association across the range of IOP, which reduces their accuracy. OBJECTIVE: To test the hypothesis that nonuniform behavior of genetic risk scores for IOP is associated with a specific type of genetic interaction. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional, post hoc genetic association studies were performed using linear and quantile regression in a sample of UK Biobank participants. Data were analyzed from January to September 2025. EXPOSURES: Ninety-eight genetic variants associated with IOP. MAIN OUTCOMES AND MEASURES: Tests were carried out for 98 genetic variants associated with IOP (P < 5.0 ×10-8) to examine (1) dominant or recessive genetic effects, (2) genotype × genotype interactions, (3) genotype × age interactions, and (4) genotype × sex interactions. RESULTS: A total of 98 235 participants (mean [SD] age, 58.1 [7.9] years; 52 168 female [53.1%]) were included in this analysis. More variants exhibited genotype × age interactions than expected by chance (14 of the 98 variants associated with IOP had at least nominal evidence of an interaction with age; P = 3.76 ×10-4). For 12 of these 14 variants, age increased rather than decreased the magnitude of the IOP vs genotype association. However, integrating age interactions into the genetic risk score construction process did not yield improved accuracy (incremental noninteraction model, R2 = 4.05; 95% CI, 3.82-4.31 and interaction model, R2 = 4.04; 95% CI, 3.80-4.27). There was little support for other types of genetic interaction. CONCLUSIONS AND RELEVANCE: In the current work, findings show minimal evidence that nonadditive allelic effects, genotype × genotype interactions, and genotype × sex interactions contributed to the nonuniform association of genetic variants with IOP across quantiles of IOP. Although a genetic risk score for IOP was more accurate in older vs younger individuals, efforts to account for genotype × age interactions in genetic risk score construction did not improve accuracy. These findings suggest other factors, such as gene-environment interactions, contribute to the nonuniform relationship of genetic variants with IOP.
PURPOSE: Low systemic blood pressure (BP) has been implicated as a risk factor for glaucoma progression. The purpose of this study was to investigate the association between 24-hour BP and rates of retinal nerve fiber layer (RNFL) loss in eyes with primary open-angle glaucoma. DESIGN: Prospective cohort study. PARTICIPANTS: Seventy-nine eyes from 42 subjects with glaucoma (mean age, 68.5 ± 7.6 years) enrolled in the Vascular Imaging in Glaucoma Study at the Bascom Palmer Eye Institute. METHODS: Participants underwent 24-hour ambulatory BP monitoring at baseline. Follow-up evaluations were conducted at 4-month intervals and included ophthalmic examination, BP measurement, and peripapillary RNFL thickness measurement with spectral-domain optical coherence tomography. The association between BP and RNFL loss over time was assessed using linear mixed-effects models adjusted for age, sex, race, baseline RNFL thickness, central corneal thickness, and intraocular pressure. MAIN OUTCOME MEASURES: The effect of baseline 24-hour mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP) on the rate of average RNFL loss over time. RESULTS: Eyes underwent an average of 13 ± 3 optical coherence tomography exams over 43 ± 10 months of follow-up. The mean rate of RNFL loss was -0.34 ± 0.64 µm/y (median: -0.32; interquartile range: -0.66 to -0.04 µm/y). After adjusting for confounding factors, every 10 mm Hg lower in 24-hour minimum MAP, SBP, and DBP was associated with -0.542 µm/y (P < .001), -0.360 µm/y (P = .003), and -0.458 µm/y (P = .008) faster RNFL loss, respectively. Eyes in the lowest quartile of average 24-hour MAP (81-90 mm Hg) and minimum 24-hour DBP (35-47 mm Hg) experienced significantly faster progression compared to those in the highest quartile, with differences of -0.68 µm/y (P = .017) and -0.63 µm/y (P = .030), respectively. CONCLUSIONS: Lower systemic BP, especially minimum MAP, SBP, and DBP measured by 24-hour ambulatory BP monitoring, is associated with faster rates of RNFL loss in primary open-angle glaucoma eyes. 24-hour BP monitoring may help predict glaucoma patients at greater risk of progression.
OBJECTIVE: The progression of glaucoma despite adequate intraocular pressure (IOP) control highlights the need for neuroprotective and neuroregenerative therapies. Preclinical studies suggest insulin promotes retinal ganglion cell survival and regeneration, but its safety in higher concentrations (100 and 500 units/mL), administered topically, has been poorly characterized in humans. We aim to assess the safety and tolerability of these two concentrations of insulin eye drops in patients with open-angle glaucoma (OAG). DESIGN: A phase I, randomized, double-blind, placebo-controlled, single-centre clinical trial. PARTICIPANTS: Patients with mild to moderate OAG were randomized 2:2:1 to receive once-daily topical insulin U-100, U-500, or placebo in 1 eye for 5 days, with follow-up visits at 1, 3, and 6 months. The primary safety outcomes include glycemia, serum potassium, ocular adverse events (AEs), and ocular tolerability scores. Secondary outcomes included IOP, best-corrected visual acuity (BCVA), retinal nerve fibre layer thickness, ganglion cell complex, visual field, and OCT angiography. RESULTS: Eighteen open-angle glaucoma patients were enrolled (mean age: 66.2 ± 10.1 years). No serious AEs related to insulin were observed. One asymptomatic, transient near-hypoglycemia event occurred in a fasting participant (3.9 mmol/L), with no recurrence after dietary adjustment. No significant changes were found in serum potassium, IOP, BCVA, visual fields, or OCT. Ocular symptoms in the insulin groups were limited to transient, mild burning sensation upon application. One participant experienced cystoid macular edema at 3 months, which was attributed to pre-existing ocular pathology. CONCLUSION: Topical insulin at 100 and 500 units/mL concentrations was well tolerated in patients for short-term use and did not result in significant systemic or ocular toxicity.
The dynamic properties of hyaluronate solutions are discussed with relevance to some problems in sensory physiology (mechanoelectrical transduction), renal physiology, interstitial fluid regulation, and especially to the causes of open-angle glaucoma. With respect to the last problem: as recent biochemical evidence indicates that the hyaloid membrane does not exist, it now seems worthwhile to consider the increase in intraocular pressure present in the eye with glaucoma to be due--at least in the open-angle case--to a change in the specific gravity and hydrophilic nature of the hyaluronic acid in the vitreous body in particular, as well as in the trabecular meshwork. Densimetric experimental evidence indicates that the hyaluronate system could, indeed, produce the pressure changes seen in glaucoma, if intraocular pH changed but slightly. A hypothesis concerning the effect of acetazol amide on intraocular pressure is also presented.
BACKGROUND/AIMS: Primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) are distinct diseases, yet many glaucoma cases in population-based datasets lack subtype specification. We assessed incidence patterns of glaucoma subtypes in China and the UK and used genetic evidence to infer the likely subtype composition of cases recorded as unspecified glaucoma. METHODS: Incident primary glaucoma was identified from linked inpatient records in the prospective China Kadoorie Biobank (CKB; n=512 504) and UK Biobank (UKB; n=492 329) studies. Cohort-specific phenotyping algorithms defined POAG, PACG and unspecified glaucoma. Adjusted incidence rates were estimated by direct standardisation. To support subtype inference, polygenic risk scores (PRSs) were constructed using ancestry-specific genome-wide association studies, including a new East Asian PACG meta-analysis, and tested for association with glaucoma phenotypes using multivariable logistic regression. RESULTS: Over 12 years of follow-up, 1658 primary glaucoma cases were identified in CKB and 7643 in UKB. Most (>68%) cases lacked subtype specification. Incidence increased with age and was twofold higher among women for PACG in both cohorts and for unspecified glaucoma in CKB. In UKB, POAG incidence was fivefold higher among Black than White participants, with a similar but attenuated pattern for unspecified glaucoma. PRS analyses indicated that unspecified glaucoma closely aligned with PACG in CKB but was more heterogeneous in UKB. CONCLUSION: Healthcare-recorded incidence patterns for POAG and PACG were consistent with established demographic risk factors, whereas unspecified glaucoma showed differences in subtype composition between populations. Integrating epidemiological and genetic evidence improves interpretation of glaucoma phenotypes when detailed clinical information is unavailable.
Every 12 hours 0.1% dipivefrin was administered to one eye and 2% epinephrine hydrochloride was administered to the fellow eye of 42 patients with primary open-angle glaucoma or ocular hypertension in a randomized, double-masked study lasting three months. Dipivefrin produced similar percent reductions in intraocular pressure (18.6%) to epinephrine (21.0%), as well as similar increases in outflow facility and pupil diameter. A significantly lower incidence of burning and stinging after drug instillation was noted with dipivefrin therapy. This study supported the contention that dipivefrin is an effective and safe alternative to epinephrine therapy for the reduction of elevated intraocular pressure.
45 patients with ocular hypertension or open-angle glaucoma were tested to see if, and to what extent timolol and three other different parasympathicomimetics (pilocarpine 2%, carbachol 1.5%, aceclydine 2%) produced an supplementary reduction of the intraocular pressure. An equally marked, additional drop in eye pressure was achieved when patients who had been given timolol over an extended period of time, were additionally treated with one dose of pilocarpine 2% or carbachol 1.5%. Aceclydine 2% produced no statistically significant additional effect. Patients who had only been treated with pilocarpine 2% over an extended period of time and then were given one dose of timolol 0.25% produced a drop in eye presure more than double that of those patients who had been primarily treated with timolol and then received pilocarpine or carbachol. These results will be discussed on the basis of the mode of action of the applied medications.
Topical treatment with 1% thymoxamine produces in rabbit and human eyes a small but real miotic and tension-lowering effect. The latter is more evident using two different models of experimental ocular hypertension in rabbits. In human open-angle glaucoma eyes, tonographic measurements indicate that the outflow facility is left unchanged by the drug.
Using the age-sex-specific data collected in the Framingham Heart Study 1948--1964 together with ophthalmic diagnoses made in the Framingham Eye Study in 1973--1975, the following variables were found to be associated with senile cataract: education, casual blood sugar, systemic blood pressure, height, vital capacity, serum phospholipid and hand strength; with senile macular degeneration: systemic blood pressure, height, vital capacity, left ventricular hypertrophy, hand strength and history of lung infection; with diabetic retinopathy: casual blood sugar, urine sugar and other specific elements of diabetes; with ocular hypertension: systemic blood pressure, height, casual blood sugar and pulse rate. No variables were identified as associated with open-angle glaucoma. The paper stresses the need for corroboration of these findings, which may be a mix of real and chance associations, and the need for additional analyses before any of these associations are considered evidence of factors related to risk of ophthalmic disease.
A patient with chronic open-angle glaucoma was suspected of having allergic dermatitis and conjunctivitis to epinephrine. He was tested with epinephrine and other active substances, the preservatives and antioxidants usually used in the preparation of eye drops. He was also tested with other possible contactants with which he had had contact. The patient showed positive allergic patch test reactions to the chloride solution of epinephrine. The patient showed an unexpected positive reaction when tested with di-isopropyl fluorophosphate (DFP). The importance of routine patch testing in ophthalmic practice to detect sensitizers in cases of contact allergy is stressed.
Theoretical aspects of laser characteristics as well as the physics parameters involved in laser trabeculotomy in open-angle glaucoma are put forward. Outflow hydrodynamics and perforation mechanism as well as the required optical matching system are evaluated in detail.
In a controlled double-blind cross-over trial in 10 patients comprising six with open-angle glaucoma, three with closed-angle glaucoma, and one with ocular hypertension, a single oral dose of atenolol (50 mg) was significantly more effective than propranolol (40 mg) in reducing ocular tension.
Pilocarpine 4% solutions at pH 4.1 and 5.8 were compared in a double-blind clinical trial on 24 eyes of patients with primary open-angle glaucoma. Each drug was used over a period of 1 week. No significant difference in the lowering of intraocular pressure was found, and the near-neutral solution of pilocarpine was found to be equally stable when compared to the acid solution over a 6-month period.
The ability to demonstrate AMPS in the trabecular region in the normal eye of the Rhesus monkey was shown to be critically dependent upon technical variation. Staining the fixed specimen prior to dehydration and embedding permits the uniform demonstration of AMPS in the trabecular region of the Rhesus monkey and shows it to be hyaluronidase-sensitive. Electron microscopy using the modified technique shows the reaction products to be present within the trabecular band, the intertrabecular spaces, and the canal of Schlemm. More impressive distribution was seen in the basement membrane of trabecular endothelium intimately related to the cell wall and in the ground substance and basement membrane of the endothelium of the inner wall of the canal Schlemm. The technique is also successful in the human eye and suggests a greater abundance of trabecular AMPS in open-angle glaucoma.
INTRODUCTION: The purpose of this study was to evaluate the capabilities of large language models such as Chat Generative Pretrained Transformer (ChatGPT) to diagnose glaucoma based on specific clinical case descriptions with comparison to the performance of senior ophthalmology resident trainees. METHODS: We selected 11 cases with primary and secondary glaucoma from a publicly accessible online database of case reports. A total of four cases had primary glaucoma including open-angle, juvenile, normal-tension, and angle-closure glaucoma, while seven cases had secondary glaucoma including pseudo-exfoliation, pigment dispersion glaucoma, glaucomatocyclitic crisis, aphakic, neovascular, aqueous misdirection, and inflammatory glaucoma. We input the text of each case detail into ChatGPT and asked for provisional and differential diagnoses. We then presented the details of 11 cases to three senior ophthalmology residents and recorded their provisional and differential diagnoses. We finally evaluated the responses based on the correct diagnoses and evaluated agreements. RESULTS: The provisional diagnosis based on ChatGPT was correct in eight out of 11 (72.7%) cases and three ophthalmology residents were correct in six (54.5%), eight (72.7%), and eight (72.7%) cases, respectively. The agreement between ChatGPT and the first, second, and third ophthalmology residents were 9, 7, and 7, respectively. CONCLUSIONS: The accuracy of ChatGPT in diagnosing patients with primary and secondary glaucoma, using specific case examples, was similar or better than senior ophthalmology residents. With further development, ChatGPT may have the potential to be used in clinical care settings, such as primary care offices, for triaging and in eye care clinical practices to provide objective and quick diagnoses of patients with glaucoma.