The ‘two global flash’ mfERG in high and normal tension primary open-angle glaucoma

PURPOSE: To analyse the sensitivity of the '2 global flash' multifocal electroretinogram (mfERG) to detect glaucomatous dysfunction in normal tension (NTG) and high tension primary open angle glaucoma (POAG) patients. METHODS: MfERGs were recorded from 20 NTG and 20 POAG patients and compared to those of 20 controls. The mfERG array consisted of 103 hexagons. Each m-sequence step started with a focal flash that could be either dark or light (m-sequence: 2--13, L(max): 200 cd/m(2), L(min): 1 cd/m(2)), followed by two global flashes (L(max): 200 cd/m(2)) at an interval of approximately 26 ms. Focal scalar products (SP) were calculated using focal templates derived from the control recordings (VERIS 4.8). We analyzed 5 response averages (central 7.5 degrees and 4 adjoining quadrants) of the response to the focal flash, the direct component at 10-40 ms (DC) and the following two components induced by the effects of the preceding focal flash on the response to the global flashes at 40-70 ms (IC-1) and at 70-100 ms (IC-2). RESULTS: Both NTG and POAG patients differed from controls in the IC-1 response to the superior quadrants, and POAG patients also differed from controls in the centre. The most sensitive parameter was the IC-1 of the superior temporal quadrant with an area under the ROC curve of 0.82 for POAG and 0.79 for NTG. The DC and the IC-2 did not differ significantly between the groups. When all five response averages of the IC-1 were taken into consideration 90% of the NTG patients and 85% of the POAG patients were correctly classified as abnormal while 80% of the control subjects were correctly classified as normal. CONCLUSIONS: This stimulus sequence holds promise for the diagnosis of early functional changes in POAG. A new finding is that both NTG, as well as POAG can be differentiated from control subjects.     

What increases outflow resistance in primary open-angle glaucoma?

Intraocular pressure, the most critical risk factor for primary open-angle glaucoma is generated in the trabecular meshwork outflow pathways, which provide resistance to aqueous humor outflow. The resistance is increased in primary open-angle glaucoma, and changes in the quality and amount of the extracellular matrix in the juxtacanalicular region of the trabecular meshwork appear to be causatively involved. The extracellular matrix changes are very likely under control of transforming growth factor-beta2 (TGF-beta2), which is found at high concentrations in the aqueous humor of patients with primary open-angle glaucoma. Additional factors are thrombospondin-1, which activates TGF-beta2 in vivo, and connective tissue growth factor, which is an important downstream mediator of the effects of TGF-beta2 on trabecular meshwork extracellular matrix turnover. In contrast, bone morphogenetic protein-7 (BMP-7) strongly antagonizes fibrogenic actions of TGF-beta2 on human trabecular meshwork cells, indicating that a pharmacological modulation of BMP-7 signalling might be a promising strategy to treat primary open-angle glaucoma.     

A sick eye in a sick body? Systemic findings in patients with primary open-angle glaucoma

Despite intense research, the pathogenesis of primary open-angle glaucoma (POAG) is still not completely understood. There is ample evidence for a pathophysiological role of elevated intraocular pressure; however, several systemic factors may influence onset and progression of the disease. Systemic peculiarities found in POAG include alterations of the cardiovascular system, autonomic nervous system, immune system, as well as endocrinological, psychological, and sleep disturbances. An association between POAG and other neurodegenerative diseases, such as Alzheimer disease and Parkinson disease, has also been described. Furthermore, the diagnosis of glaucoma can affect the patient's quality of life. By highlighting the systemic alterations found in POAG, this review attempts to bring glaucoma into a broader medical context.     

Normal-tension glaucoma: is it different from primary open-angle glaucoma?

PURPOSE OF REVIEW: Normal-tension glaucoma (NTG) is a common form of open-angle glaucoma throughout the world, and yet there are many unanswered questions regarding both the mechanisms of the optic neuropathy and the treatment of these patients. The present review considers how recent literature advances our understanding of both the mechanisms of glaucomatous damage and the treatment of patients with NTG. RECENT FINDINGS: The main theme in the current literature continues to be that NTG and primary open-angle glaucoma (POAG) represent a continuum of open-angle glaucomas, in which a certain level of intraocular pressure (IOP) is the predominant causative risk factor in POAG, while additional IOP-independent factors take increasing importance in NTG. There is considerable overlap between the two conditions, however, and within the population of NTG patients there are subsets in which IOP, blood flow and other factors assume relative importance. SUMMARY: In clinical practice, control of IOP remains the mainstay of managing NTG patients, but consideration must also be given to other factors, especially those that may influence perfusion of the optic nerve head. Treatment paradigms will likely change as researchers continue to investigate the mechanisms of glaucomatous optic neuropathy and search for IOP-independent neuroprotective agents.     

Ab-externo precise localization of Schlemm’s canal in patients with primary open-angle glaucoma北大核心

Objective To investigate the ab-externo approach for the precise localization of the Schlemm’s canal (SC) in patients with primary open-angle glaucoma (POAG). Methods A total of 40 POAG patients (40 eyes) who underwent ab-externo SC-related surgeries in Weifang Eye Hospital from August 2020 to October 2021 were selected. According to the intraoperative measuring method, the patients were randomly divided into the high-definition (HD) image group and the sterile drawing group, with 20 patients (20 eyes) in each group. In the HD image group, HD images of the surgical area were captured by a microscope for measurement of the distance between loci. In the sterile drawing group, the loci were marked on the sterile drawing with a mapping compass under the microscope before measurement of their distance. The boundary line between the semitransparent and non-transparent tissues was marked by the sclerotic scatter and used as the base line (BL). A blood reflux band of SC was found on the scleral bed by the transillumination in the anterior chamber with the fiber optic endoscope. The outer wall of SC was removed completely during the operation for measuring related indexes, such as the width of SC (SW), the distance between the BL and the posterior edge of SC (d1), the distance between the conjunctival insertion line (CIL) and the anterior edge of SC (d2), and the distance between the BL and the CIL (d3). The white-to-white (WTW) distance and axial length (AL) were measured with IOL-Master before surgery. Differences and correlations among these indexes were analyzed. Results d2 [(1.85±0.28) mm] and d3 [(2.63±0.30) mm] in the HD image group were higher than those [d2: (1.61±0.37) mm and d3: (2.41±0.38) mm] in the sterile drawing group, and the differences were statistically significant (both P<0.05). WTW and d1 were positively correlated with AL (both P<0.05), d1 and d2 were positively correlated with d3 (both P<0.05) in both groups, while the rest indexes had no significant correlation (all P>0.05). The 40 eyes were divided into 3 groups according to AL: short AL group (AL<23 mm), medium AL group (23 mm≤AL<25 mm), and long AL group (AL≥25 mm). d1 in the short, medium, and long AL groups were (0.30±0.08) mm, (0.37±0.10) mm, and (0.57±0.09) mm, respectively, and the differences among the three groups were statistically significant (F=14.915, P<0.05). d1 in the long AL group was longer than that in the short and medium AL groups (both P<0.05). Conclusion The transillumination system can clearly display the SC blood reflux band on the deep scleral bed, facilitating the precise localization of SC. d1 is positively correlated with AL in POAG patients. © The Author(s) 2023.     

Is primary open-angle glaucoma an ocular manifestation of systemic disease?

Graefe's Archive for Clinical and Experimental Ophthalmology - Primary open-angle glaucoma is currently characterized by a pattern of progressive retinal ganglion cell loss that stems from a...     

Screening for primary open-angle glaucoma in the developed world: are we there yet?

BACKGROUND: In 1995, the Quebec Agency for Health Services and Technology Assessment (AETMIS) stated that a formal screening program for primary open-angle glaucoma (POAG) could not be recommended for the province of Quebec, owing to "a high degree of uncertainty and because of the high cost such a program would entail." The purpose of this article was to evaluate the possibility of instituting a POAG screening program in light of recent advances in the diagnosis and treatment of glaucoma. METHODS: We reviewed new developments that have occurred since the mid to late 1990s in the field of glaucoma. Changes that could positively influence the feasibility and organization of future glaucoma screening programs were identified. RESULTS: New technologies, including confocal scanning laser ophthalmoscopy (HRT II), optical coherence tomography (Stratus OCT), and scanning laser polarimetry with variable corneal compensation (GDx-VCC), permit early detection of optic nerve and nerve fibre layer structural damage. Together with advanced psychophysical tests (frequency doubling perimetry and short wavelength automated perimetry) for earlier detection of functional damage, they provide an increased understanding of the diagnosis and monitoring of POAG. Elevated intraocular pressure (IOP) remains the most important risk factor for glaucoma. Clinical trials indicate that lowering IOP at different stages of the disease can arrest or decrease its rate of progression. Moreover, it is important to assess pachymetry because IOP measurements are influenced by central corneal thickness. Finally, new treatments, such as prostaglandin analogues or selective laser trabeculoplasty, are safer and may also achieve lower intraocular pressures. INTERPRETATION: Health policy involves the investment of public resources, and cost-effectiveness analyses for POAG screening are heavily weighted by the degree of uncertainty that glaucoma screening can be effectively and reliably achieved. The many new developments and advancements outlined herein, combined with the possible increasing prevalence of POAG, necessitate the re-evaluation of screening for primary open-angle glaucoma.     

Medical treatment patterns of ASCRSmembers for primary open-angle glaucoma — 1998 survey

A survey of medical treatment patterns of primary open-angle glaucoma (POAC) wasmailed to all United States members of the American Society of Cataract and Refractive Surgery (ASCRS) in March 1988, 21.2% responded. Demographic information pertinent to glaucoma care was also obtained. The use of diagnostic ancillary tests, as well as the sequential order of preferred therapy in 3 hypothetical patient populations was analyzed: patients with mild, moderate and advanced POAC. Preferred medical therapy was cross-tabulated with number of years in practice fellowship training in glaucoma, and geographic location.     

Abnormal systemic and ocular vascular response to temperature provocation in primary open-angle glaucoma patients: a case for autonomic failure?

PURPOSE: To assess systemic and ocular vascular reactivity in response to warm and cold provocation in untreated patients with primary open-angle glaucoma and normal control subjects. METHODS: Twenty-four patients with primary open-angle glaucoma and 22 normal control subjects were subjected to a modified cold pressor test involving immersion of the right hand in 40 degrees C warm water followed by 4 degrees C cold water exposure, and finger and ocular blood flow were assessed by means of peripheral laser Doppler flowmetry and retinal flowmetry, respectively. Finger and body temperature as well as intraocular pressure, systemic blood pressure, systemic pulse pressure, heart rate, and ocular perfusion pressure were also monitored. RESULTS: The patients with glaucoma demonstrated an increase in diastolic blood pressure (P = 0.023), heart rate (P = 0.010), and mean ocular perfusion pressure (P = 0.039) during immersion of the tested hand in 40 degrees C water. During cold provocation, the patients demonstrated a significant decrease in finger (P = 0.0003) and ocular blood flow (the parameter velocity measured at the temporal neuroretinal rim area; P = 0.021). Normal subjects did not demonstrate any blood flow or finger temperature changes during immersion of the tested hand in 40 degrees C water (P > 0.05); however, they exhibited increases in systolic blood pressure (P = 0.034) and pulse pressure (P = 0.0009) and a decrease in finger blood flow (P = 0.0001) during cold provocation. In normal subjects, the ocular blood flow was unchanged during high- and low-temperature challenge. CONCLUSIONS: Cold provocation elicits a different blood pressure, and ocular blood flow response in patients with primary open-angle glaucoma compared with control subjects. These findings suggest a systemic autonomic failure and ocular vascular dysregulation in POAG patients.     

【In Press】 Comparison of total/active ghrelin levels in primary open-angle glaucoma, pseudoexfoliation glaucoma and pseudoexfoliation syndrome

AIM: To investigate the levels of ghrelin (Gh), acylated-ghrelin (AGh) and AGh/Gh ratio in the humor aqueous (HA) of cases with pseudoexfoliation syndrome (PXS), pseudoexfoliation glaucoma (PXG), primary open angle glaucoma (POAG) and to compare these with control subjects. METHODS: A prospective examination was made of the total-Gh, and AGh levels of HA of 67 patients undergoing cataract surgery. Patients were divided into 4 groups. HA samples were aspirated at the beginning of the surgery, stored at -70℃ Gh and AGh quantification was performed with ELISA kits, the AGh/total-Gh ratios were calculated. ANOVA, Kruskal-Wallis, Chi-Square and post-hoc tests were used for statistical analysis. RESULTS: Total-Gh levels in HA were 189.2±45.6 pg/mL in the control group, 199.2±32.9 pg/mL in PXS, 180.6±20.9 pg/mL in PXG and 176.8±21.4 pg/mL in POAG groups (P>0.05). AGh levels in HA were 23.09±5.01 pg/mL in the control group, 24.13±5.22 pg/mL in PXS, 22.29±1.55 pg/mL in PXG and 19.69±2.93 pg/mL in POAG groups (P>0.05). The ratio of AGh/Gh was 10.3%±2.34% in the control group, 13.03%±2.58% in PXS, 12.3%±1.54% in PXG and 11.79%±1.41% in POAG groups (P=0.044). The difference between the PXS and control groups was significant (P=0.030). CONCLUSION: In spite of statistically insignificant results, the HA total-Gh levels were lower than those of the control subjects but not parallel with the AGh levels in glaucoma patients. The relative increase in the AGh/Gh ratio in glaucoma cases supports the view that proportional increases of AGh might play a role in the pathogenesis of glaucoma.     

Do motivational cards really benefit sibling screening of primary open-angle glaucoma probands?

Purpose:To compare the impact of Sibling Motivational Card (SMC) and oral counseling in screening siblings of primary open-angle glaucoma (POAG) probands.Methods:Two hundred and thirty-four newly diagnosed POAG probands were randomized to receive either oral counseling or SMC to motivate their siblings for a glaucoma screening at a tertiary eye care hospital in South India from July 2015 and June 2017. A total of 116 probands were orally counseled with a standard template of dialogs about the importance of family screening to motivate their siblings for a screening. One hundred and eighteen probands were randomized to receive SMC, bearing the details of the proband, sibling, and a message stressing the importance of family screening, in addition to oral counseling. We assessed the response rate in each group. Additionally, we evaluated the prevalence of POAG in the siblings.Results:A total of 95 siblings of 234 POAG probands were screened. The mean age distribution was 53.33 ± 10.9 years (range 28–79 years). The male to female ratio was 3:4. The percentage of siblings screened was more in the oral counseling group (63.2%) than in the SMC group (36.8). About 43 (45%) siblings had some form of glaucoma, and 13.6% had POAG. An additional 22.1% were disk suspects, and 5.2% had ocular hypertension.Conclusion:SMC did not have an additional benefit over the standard oral counseling in promoting sibling screening. Our study stresses the importance of sibling screening in POAG probands. Targeting siblings of POAG probands with oral counseling may offer a relatively inexpensive way of detecting glaucoma.     

Characterizing the “POAGome”: A bioinformatics-driven approach to primary open-angle glaucoma

Primary open-angle glaucoma (POAG) is a genetically, physiologically, and phenotypically complex neurodegenerative disorder. This study addressed the expanding collection of genes associated with POAG, referred to as the “POAGome.” We used bioinformatics tools to perform an extensive, systematic literature search and compiled 542 genes with confirmed associations with POAG and its related phenotypes (normal tension glaucoma, ocular hypertension, juvenile open-angle glaucoma, and primary congenital glaucoma). The genes were classified according to their associated ocular tissues and phenotypes, and functional annotation and pathway analyses were subsequently performed. Our study reveals that no single molecular pathway can encompass the pathophysiology of POAG. The analyses suggested that inflammation and senescence may play pivotal roles in both the development and perpetuation of the retinal ganglion cell degeneration seen in POAG. The TGF-β signaling pathway was repeatedly implicated in our analyses, suggesting that it may be an important contributor to the manifestation of POAG in the anterior and posterior segments of the globe. We propose a molecular model of POAG revolving around TGF-β signaling, which incorporates the roles of inflammation and senescence in this disease. Finally, we highlight emerging molecular therapies that show promise for treating POAG.     

Visual field defects and normal nerve fiber layer: may they coexist in primary open-angle glaucoma?

The retinal nerve fiber layer (RNFL) is the anatomical structure most sensitive to glaucoma injury. Before a functional loss such as a visual field defect is displayed, a large number of nerve fibers can be damaged. However, there are glaucoma patients in which an apparently normal RNFL coexists with evident visual field defects. A total of 54 eyes affected with primary open-angle glaucoma were studied. Visual field was examined with the Humphrey Field Analyzer (Zeiss) using program 30-2. The Nerve Fiber Analyzer II (Laser Diagnostic Technologies) was used to study the RNFL of these patients. Mean deviation of the visual field ranged from 6 to 31 dB in all eyes that were examined. The average thickness of the RNFL ranged from 20 to 90 microm. According to our previous experience 75 microm was fixed as the cutoff between normal and pathological values of RNFL thickness. We identified 5 eyes with a RNFL thickness over 75 microm and a visual field with a mean deviation over 6 dB; 9% of the studied eyes were found to have a visual field defect with no changes in RNFL. We conclude that not all subjects have the same number of fibers at birth and that it is therefore possible to underestimate the RNFL changes. Our study illustrates that the concept of normal and altered has to be considered as a relative one for all the aspects characterizing the glaucomatous disease.