RETeval Portable Electroretinogram Parameters in Different Severity Stages of Glaucoma.

PRéCIS:: Four parameters of the noninvasive, portable RETeval electroretinogram (ERG) system were found to correlate with visual field mean deviation and optical coherence tomography (OCT) thickness parameters, and may therefore be suitable for glaucoma detection. PURPOSE: To investigate the RETeval full-field ERG parameters for accuracy of separating glaucoma and normal eyes, and correlation with glaucoma severity. PATIENTS AND METHODS: Sixty-two eyes of 62 primary open-angle glaucoma patients [visual field mean deviation (MD) range: -0.44 to -31.15 dB] and 39 eyes of 39 healthy controls underwent one RETeval test (photopic negative response protocol), OCT imaging, and Humphrey 30-2 visual field testing. The glaucoma patients were divided into early (MD≥-6dB, n=33) and moderate-to-advanced (MD<-6 dB, n=29) groups. RESULTS: Significant correlations were found between the best-performing 4 RETeval ERG parameters and the glaucoma severity measures (MD and OCT thickness parameters) for all eyes, all glaucoma eyes and the moderate-to-advanced glaucoma eyes [photopic negative response amplitude at 72 ms (PhNR 72) and MD: r=-0.333, -0.414, and -0.485, respectively, P≤0.008; PhNR 72 and average circumpapillary retinal nerve fiber layer thickness; r=-0.429, -0.450, and -0.542, respectively, P≤0.002]. Except for P-ratio, there was no significant difference between the area under the receiver-operating characteristic (AUROC) values of the OCT thickness parameters (range: 0.927 to 0.938) and the 4 best-performing RETeval ERG parameters (range: 0.839 to 0.905) in the early glaucoma versus control separation. For differentiating the control and the moderate-to-advanced glaucoma eyes, the AUROC values of the 4 best-performing RETeval ERG parameters ranged between 0.924 and 0.958, and no significant difference was found between them and those of the OCT parameters. CONCLUSIONS: The noninvasive, portable RETeval full-field ERG device may be useful to detect glaucoma in moderate-to-advanced stages.

Is "normal tension glaucoma" glaucoma?

Primary open angle glaucoma (POAG) represents a distinct disease entity with elevated intraocular pressure (IOP) as the main risk factor, even though the reasons for why the IOP is elevated remains to be elucidated. It is considered that normal tension glaucoma (NTG) is a subtype of POAG, comprising a special form of glaucomatous neurodegeneration or glaucomatous optic neuropathy (GON) almost exactly the same as that seen in POAG, but the IOP, as named, remains in the statistically normal range. Actually the disease entity of NTG has been a profound confusion and it is difficult to be accurately conceptualized. One of the reasons is that the IOP is closely linked to the occurrence of GON in POAG but not in NTG, and for the latter, it seems that GON is secondary to a number of local or systemic disorders. In recent years, increasing evidences suggest that NTG or IOP independent GON is a non-glaucomatous disease with different disease entities from POAG and with more diverse and complex etiologies. Here we hypothesized that NTG, at least for those with recognizable primary diseases, is not a glaucomatous disease; instead, it represents a group of disorders with GON as a characteristic clinical feature or phenotype.

Twenty-four-hour pattern of intra-ocular pressure in untreated patients with primary open-angle glaucoma.

PURPOSE: To investigate and compare the 24-hr intra-ocular pressure (IOP) pattern among different severities of glaucomatous optic neuropathy (GON) together with different subtypes of primary open-angle glaucoma (POAG). METHODS: The IOPs of untreated patients with POAG were measured every 2 hrs over a 24-hr period. Subjects were divided into mild, moderate and severe groups according to the glaucoma staging system 2. The two POAG subtypes, normal tension glaucoma (NTG) and hypertension glaucoma (HTG) were classified according to peak IOP values throughout the 24-hr period. The 24-hr IOP curves were obtained based on the average IOP value at each time-point. The mean, peak, trough and fluctuation of IOP together with the diurnal-to-nocturnal IOP change were calculated and compared among different groups. RESULTS: A total of 160 POAG patients (84 NTG and 76 HTG) were enrolled in the study. Generally, IOP decreased in the diurnal period and increased progressively during the nocturnal period, with peak IOP occurring from 2:00 AM to 10:00 AM. The average IOP values at all time-points were significantly higher in the mild group compared to the moderate and severe groups (p < 0.05). Compared with the NTG subjects, the IOP parameters including mean, peak, trough and fluctuation were significantly higher in the HTG subjects (p < 0.001), and IOP increased more predominantly in the HTG subtype during the nocturnal period. CONCLUSIONS: There was some regularity in the 24-hr IOP pattern in POAG, but different severities of GON and different subtypes might present different characteristics. Other non-IOP factors may lead to pathological IOP fluctuation and could be correlated with GON.

Estimation of the Disc Damage Likelihood Scale in primary open-angle glaucoma: the Glaucoma Stereo Analysis Study.

PURPOSE: The Glaucoma Stereo Analysis Study (GSAS), a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX) to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients. We examined the associations between the Disc Damage Likelihood Scale (DDLS), a grading system for estimating glaucomatous ONH damage, and each parameter. METHODS: The study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. ONH morphological parameters including the DDLS stage were calculated with prototype analysis software. Three independent graders classified each optic disc appearance into four different types: focal ischemic, myopic glaucomatous, senile sclerotic, and generalized enlargement. The correlations between the DDLS and patient characteristics or each ONH parameter were analyzed with Spearman's rank correlation coefficient. RESULTS: The DDLS was correlated positively with baseline intraocular pressure and visual field pattern standard deviation, and negatively with visual field mean deviation. The DDLS was strongly correlated with vertical cup-to-disc ratio and horizontal cup-to-disc ratio positively, and with minimum rim-disc ratio negatively. The mean DDLS stage in the myopic glaucomatous type tended to be higher than the scores in other types. CONCLUSION: The DDLS obtained through three-dimensional ONH analysis correlates well with the severity of glaucomatous ONH and visual field damage.

Characteristic correlations of the structure-function relationship in different glaucomatous disc types.

PURPOSE: To investigate the influence of the optic disc type on the overall and regional correlation between structure and function in open angle glaucoma (OAG). METHODS: We divided 144 eyes of 144 patients with OAG into four groups according to Nicolela et al.'s classification of optic disc type: focal ischemic (FI), myopic glaucomatous (MY), senile sclerotic (SS), and generalized enlargement (GE). We measured the circumpapillary retinal nerve fiber layer thickness (cpRNFLT) with the 3D OCT-2000 and the mean deviation (MD) with the Humphrey Field Analyzer in each group and determined the influence of the disc type on these parameters with the Spearman rank correlation. RESULTS: We found that cpRNFLT and MD were significantly correlated in the MY (r = 0.61, P < 0.001), GE (r = 0.62, P < 0.001), and SS groups (r = 0.52, P = 0.002), but not in the FI group (r = 0.25, P = 0.130). The region of the optic disc with the highest correlation coefficient between structure and function differed according to the disc type. CONCLUSIONS: The correlation between cpRNFLT and MD varied according to the optic disc morphology in OAG. This suggests that different disc types have characteristic regional variations in the correlation between structure and function. The disc type should therefore be considered in investigations of the correlation between structure and function in glaucoma.

A hierarchical cluster analysis of normal-tension glaucoma using spectral-domain optical coherence tomography parameters.

PURPOSE: Normal-tension glaucoma (NTG) is a heterogenous disease, and there is still controversy about subclassifications of this disorder. On the basis of spectral-domain optical coherence tomography (SD-OCT), we subdivided NTG with hierarchical cluster analysis using optic nerve head (ONH) parameters and retinal nerve fiber layer (RNFL) thicknesses. PATIENTS AND METHODS: A total of 200 eyes of 200 NTG patients between March 2011 and June 2012 underwent SD-OCT scans to measure ONH parameters and RNFL thicknesses. We classified NTG into homogenous subgroups based on these variables using a hierarchical cluster analysis, and compared clusters to evaluate diverse NTG characteristics. RESULTS: Three clusters were found after hierarchical cluster analysis. Cluster 1 (62 eyes) had the thickest RNFL and widest rim area, and showed early glaucoma features. Cluster 2 (60 eyes) was characterized by the largest cup/disc ratio and cup volume, and showed advanced glaucomatous damage. Cluster 3 (78 eyes) had small disc areas in SD-OCT and were comprised of patients with significantly younger age, longer axial length, and greater myopia than the other 2 groups. CONCLUSIONS: A hierarchical cluster analysis of SD-OCT scans divided NTG patients into 3 groups based upon ONH parameters and RNFL thicknesses. It is anticipated that the small disc area group comprised of younger and more myopic patients may show unique features unlike the other 2 groups.

[Is normal-tension glaucoma different from primary open-angle glaucoma].

Based on the clinical consideration, Chinese glaucoma specialist reached a consensus (2008) that normal-tension glaucoma (NTG) is a subtype of primary open-angle glaucoma (POAG), and the dividing line is whether the intraocular pressure (IOP) more than 21 mm Hg or not. But it is still a controversial problem in the world that whether NTG is different from POAG or not. Some studies have confirmed that the pathogenesis of optic neuropathy, clinical features, risk factors for glaucomatous optic neuropathy progression and treatment strategy in NTG are different from those of POAG, indicating that they may be two different disorders.

Different types of optic disc shape in patients with advanced open-angle glaucoma.

PURPOSE: To study the characteristics of patients with advanced open-angle glaucoma. METHODS: A hospital-based retrospective study was performed. Advanced glaucoma was defined as visual acuity of 0.3 or less, or mean deviation of -24 dB or less. First, we screened patients with advanced glaucoma and classified their glaucoma types. For patients with open-angle glaucoma (OAG), including both primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG), disc types were classified into four groups: focal ischemic (FI), myopic glaucomatous (MY), senile sclerotic (SS), and generalized cup enlargement (GE). RESULTS: After checking the medical history of 750 glaucoma patients, we classified 141 (18.8%) as having the advanced stage of the disease. The proportion of patients with advanced OAG was 47% (28% POAG, 19% NTG). The classification of optic disc appearances in OAG patients showed that in patients with POAG the predominant disc type was GE (P = 0.0012) and in those with NTG it was MY (P < 0.0001). CONCLUSION: In OAG patients in this study with severe glaucomatous damage, the predominant disc phenotype was GE in patients with POAG and MY in those with NTG.

Tumor necrosis factor-alpha concentrations in the aqueous humor of patients with glaucoma.

PURPOSE: To investigate the concentration of tumor necrosis factor (TNF)-alpha in the aqueous humor of patients with glaucoma, including correlations with glaucoma subtypes and intraocular pressure. METHODS: The study population comprised 84 patients with open-angle glaucoma who were scheduled for filtration or cataract surgery. Glaucoma subgroups included 29 cases of primary open-angle glaucoma (POAG), 28 cases of normal-tension glaucoma (NTG), and 27 cases of exfoliation glaucoma (ExG). Seventy-nine patients with senile cataract were recruited as control subjects. The concentrations of TNF-alpha in the aqueous humor were measured with an enzyme-linked immunosorbent assay. The percentages of samples positive for TNF-alpha and the measured concentrations in the glaucoma and cataract groups were compared. In addition, the relationships with the glaucoma subtypes, intraocular pressure, and glaucoma severity were analyzed. RESULTS: A significantly higher percentage of subjects in the glaucoma group were positive for TNF-alpha compared with the cataract group (P = 0.011). The mean TNF-alpha concentrations among the positive cases were not different between the groups (P = 0.689). TNF-alpha-positive samples were higher in the POAG (13.7%) and NTG (10.7%) subgroups than in the cataract group without significance, but higher in ExG subgroup (29.6%) with significance (P = 0.001). Relationships between the TNF-alpha concentration and the intraocular pressure or the clinical stage of glaucoma were not observed. CONCLUSIONS: TNF-alpha levels were significantly higher in the glaucoma group than in the cataract group, with a particularly large difference observed in those with ExG. The results suggest that TNF-alpha plays a key role in the progression of glaucoma.

Corneal thickness measurements in normal-tension glaucoma workups: is it worth the effort?

PURPOSE: To correlate central corneal thickness (CCT) and intraocular pressure (IOP) with disease severity in normal-tension glaucoma (NTG) patients. METHODS: We conducted a retrospective review of all patients diagnosed with NTG in our institution between 2002 and 2006. NTG was diagnosed according to the glaucomatous visual fields loss, glaucomatous optic disc cupping, and an IOP <22 mm Hg on diurnal curve measurements. Mean CCT and IOP values before and after treatment were also evaluated. Patients were divided into 3 groups according to advanced glaucoma intervention score (mild, moderate, and severe visual field defects). RESULTS: A total of 33 females and 35 males with bilateral NTG were enrolled. The mean follow-up was 4.6 years. CCT was inversely correlated with glaucoma severity. CCT was normal in both eyes in mild disease, thin in the right eye (RE) and normal in the left eye (LE) in moderate disease, and low in both eyes in severe disease. Initial bilateral mean maximal IOP was similar at all disease stages and became lower after treatment in parallel to disease severity: 13.44, 12.22, and 11.63 mm Hg in the RE and 13.29, 12.60, and 12.32 mm Hg in the LE, respectively. There was no statistical difference in disease severity between the RE and LE. CONCLUSIONS: CCT correlated with disease severity: the more advanced the disease, the thinner the cornea. Initial maximal IOP did not predict disease severity, but it was lower in the more severe cases after treatment, possibly representing a more aggressive treatment protocol.