Neural conduction in the visual pathways in ocular hypertension and glaucoma.

To compare the hemifield asymmetry of visual field (VF) loss in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) across all severity levels. A total of 522 eyes of 327 patients with POAG (mean age ± SD, 54.1 ± 12.4 years) and 375 eyes of 204 patients with PACG (67.3 ± 8.9 years) were included. Subjects meeting the definitions of POAG or PACG were included. Means of the total deviation (TD) values (Humphrey 24-2 VF) in the Glaucoma Hemifield Test (GHT) regions were calculated in early (≥ -6 dB), moderate (< -6 dB and ≥ -12 dB), and advanced (< -12 dB) stages of POAG and PACG eyes. Then the differences of the TD values between superior and inferior hemifield GHT regions of POAG and PACG eyes were calculated. Also, the relationship between the values of pattern SD (PSD) and mean TD (mTD) was compared between POAG and PACG. In POAG eyes in the early stage, three regions (central, paracentral, and peripheral) in the superior hemifield had greater loss than their inferior counterparts; in moderate and advanced stages, all GHT regions in the superior hemifield had greater loss than their inferior counterparts. In PACG eyes, siginificantly fewer regions in the superior hemifield were significantly worse than their inferior counterpart, compared with POAG: one region (central) in early stage, two regions (central and peripheral) in moderate stage, and one region (central) in advanced stage. POAG eyes had greater PSD values than PACG eyes for given mean of TD values. In both POAG and PACG eyes, VF damage was more pronounced in superior hemifield than inferior hemifield; however, this tendency was more obvious in POAG eyes than in PACG eyes.

Visual electrophysiological responses in subjects with cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

This study aimed to assess vascular endothelial function in patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG) by measuring: (a) endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery, and (b) circulating endothelial progenitor cells, which are believed to support the integrity of the vascular endothelium. We enrolled 25 patients with OHT, 23 with POAG and 26 control subjects, all of whom were aged < 65 years and had no medical history of cardiovascular disease or cardiovascular risk factors. All subjects underwent a complete ophthalmological examination, biochemistry study, assessment of cardiovascular parameters, brachial artery ultrasound assessment of endothelium-dependent FMD, generic circulating progenitor cell (CPC) and circulating endothelial progenitor cell (EPC) count with the use of flow cytometry. Flow-mediated vasodilation values differed significantly in OHT (4.5 +/- 1.1%; p = 0.021) and POAG (4.0 +/- 0.9%; p = 0.003) patients compared with controls (7.7 +/- 0.8%). The CD34(+) KDR(+) EPC count was markedly lower in OHT (28.0 +/- 5.0; p < 0.001) and POAG (24.3 +/- 3.4; p < 0.001) patients compared with controls (73.1 +/- 8.1). Neither FMD not EPCs differed significantly between OHT and POAG patients. No significant differences in CPC count or cardiovascular parameters were found among OHT or POAG patients and controls. The levels of CD34(+) KDR(+) EPCs were directly correlated (p = 0.043) with FMD, and inversely correlated (p = 0.032) with baseline intraocular pressure in OHT and POAG patients. Both OHT and POAG patients without cardiovascular risk factors have previously unreported severely reduced circulating EPCs and reduced FMD, both of which are indicators of endothelial dysfunction and increased risk of cardiovascular events.

Purpose:Aerobic exercise (AE) has been reported to decrease intraocular pressure (IOP) in healthy subjects and there are concomitant morphological changes in the anterior segment of the eye including the Schlemm’s canal (SC). However, its effects on IOP and SC morphology in glaucoma patients had not been studied before. We aim to investigate the effect of AE on the IOP and SC dimension in both healthy and primary open-angle glaucoma (POAG) eyes.Methods:The area and diameter of SC and IOP were measured in 35 primary open-angle glaucoma (POAG) patients (59 eyes) and 36 healthy subjects (72 eyes) before and after performing moderate intensity of AE by running on a treadmill for 30 min. SC was imaged by swept-source optical coherence tomography (SS-OCT) for evaluation.Results:In comparison with baseline values, mean IOP decreased significantly following AE in both POAG and healthy eyes (both P < 0.001), in which POAG eyes showed a greater degree of reduction compared to healthy eyes (P = 0.002). In comparison with baseline values, in both POAG and healthy eyes, the average cross-sectional area (POAG: 80.48 +/- 59.54 vs. 99.20 +/- 54.87 pixels; healthy: 151.84 +/- 52.76 vs. 198.23 +/- 53.70 pixels; both P < 0.001) and diameter (POAG: 3.73 +/- 1.69 vs. 4.33 +/- 1.74 pixels; healthy: 5.61 +/- 1.02 vs. 6.47 +/- 1.20 pixels; both P < 0.001) of SC significantly increased after AE. In POAG, both treated and untreated with IOP-lowering medications, a significant reduction in mean IOP and increase in SC dimensions following AE were observed (all P < 0.05), and there were no significant differences of such measurements between the two subgroups (all P > 0.05).Conclusion:AE-induced reduction in IOP and an increase in SC dimensions in POAG eyes as in healthy eyes. Further studies to evaluate the long-term effect of AE on IOP control and SC morphology in POAG seem warranted.

PurposeTo document the diurnal intraocular pressure (IOP) profile with rebound tonometry performed by primary glaucoma patients in non-clinic environment.Patients and methodsFifty-three medically-treated eyes of 31 primary angle closure glaucoma (PACG) and 22 primary open angle glaucoma (POAG) patients with no previous eye surgery were recruited. Diurnal IOP was measured 5 times per day at four-hourly intervals from 08:00 to 24:00 for 1 week in patients’ study eye using rebound tonometry in a non-clinic environment. The diurnal IOP profiles were compared between PACG and POAG eyes.ResultsFor both PACG and POAG eyes, mean patient-measured IOP was highest in the morning, gradually decreased over the course of a day, and was lowest by midnight (p < 0.001). The diurnal IOP fluctuation ± 1 standard deviation (SD), as documented by SD in daily IOP values, was lower in PACG group (1.6 ± 1.1 mmHg) than in POAG group (2.0 ± 1.2 mmHg; p = 0.049). The mean trough IOP ± 1 SD was higher in PACG group (12.9 ± 2.8 mmHg), compared to POAG group (11.5 ± 3.8 mmHg; p = 0.041). The mean IOP level at midnight ± 1 SD in PACG group (14.0 ± 3.2 mmHg) was higher than that in POAG group (12.1 ± 3.7 mmHg; p = 0.013).ConclusionsIOP in primary glaucoma patients was highest in the morning, and decreased over the course of a day in non-clinic environment. Treated diurnal IOP fluctuation seemed to be greater in POAG than PACG eyes.

To observe the diurnal variations of intraocular pressure (IOP) measured with dynamic contour tonometer (DCT) in primary open angle glaucoma (POAG) patients, normal tension glaucoma (NTG) patients, and healthy controls, and to compare the differences of diurnal variation curves between the two eyes of each subject and define the distribution of the peak of IOP; to analyze the diurnal variation range of ocular pulse amplitude (OPA) and compare the differences among the POAG and NTG patients and healthy controls. DCT was used to measure the diurnal variations of IOP and OPA in the two eyes of 18 POAG patients, 17 NTG patients and 30 normal controls at 5:00, 7:00, 10:00, 14:00, 18:00, and 22:00 and the distribution of the peak IOP was observed. The range of the diurnal variation of OPA was identified. The diurnal variation curves of IOP were different among the POAG patients, NTG patients, and normal people, and also between the two eyes of each subject. Four right eyes (13.3%) and 6 left eyes (20.0%) of the healthy controls, 4 right eyes (23.5%) and 5 left eyes (29.4%) of the NTG patients, and 5 right eyes (27.8%) and 4 left eyes (22.2%) of the POAG patients reached the peak IOP values in out-office period. Diurnal variation of OPA was detected in both the patients and controls, and the variation curves were different within different groups sampled and between the two eyes of each subject. The diurnal OPA range of the right and left eyes of the POAG group were (2.1 +/- 1.3) mm Hg, and (2.4 +/- 1.9) mm Hg respectively, significantly larger than those of the normal controls [(1.1 +/- 0.5) mm Hg and 1.2 +/- 0.5) mm Hg respectively], and those of the NTG group [(1.1 +/- 0.8) mm Hg and (1.0 +/- 0.5) mm Hg) respectively] (all P < 0.01). OPA has diurnal variation. The diurnal variation of the POAG patients is the largest. NTG patients and normal controls have asymmetric IOP and OPA diurnal variations. The two eyes of the same individual cannot always be treated as the same. The value of IOP measured in the office-time cannot completely represents the 1 d IOP.

Glaucoma patients had a reduction in the inner annulus peripapillary choroidal microvascular density (PCMD) that became worse as the glaucoma severity progressed, which might provide new evidence supporting the vascular theory. To compare PCMD among normal tension glaucoma (NTG), primary open angle glaucoma (POAG), and healthy controls using optical coherence tomography (OCT) angiography (OCTA). The study included 40 POAG, 25 NTG, and 33 healthy controls. All subjects underwent OCT and OCTA testing. The inner annulus and outer annulus PCMD, as well as peripapillary vessel density (VD), were calculated. One-way analysis of variance was used to compare the vascular parameters of the 3 groups. Pearson correlation analysis or Spearman correlation test was used to evaluate the correlation between PCMD and glaucomatous severity factors. The spatial positional relationship between PCMD and corresponding peripapillary retinal nerve fiber layer (RNFL) thickness and visual field (VF) mean deviation (MD) was also assessed. The average and 4 quadrants of the inner annulus PCMD and peripapillary VD in the 2 glaucomatous groups were significantly lower than in normal eyes ( P <0.05). Strong correlations were found between inner annulus PCMD and VF MD, peripapillary VD, and RNFL in POAG patients. Similarly, the inner annulus PCMD in NTG patients was strongly correlated with peripapillary VD and RNFL (all r >0.5). Strong positional correlations were found between inner superior quadrantal PCMD and RNFL thickness in both POAG and NTG patients ( r =0.566 and 0.731, respectively). Likewise, inner inferior quadrantal PCMD exhibited a strong correlation with RNFL thickness in POAG patients ( r =0.608). Strong positional correlations were also found between inner superior PCMD and VF MD in both POAG and NTG patients ( r =0.589 and 0.622, respectively). Inner inferior PCMD exhibited a moderate correlation with VF MD in both POAG and NTG patients ( r =0.487 and 0.440, respectively). The study found that the inner annulus PCMD decreased to varying degrees in NTG and POAG patients. The inner annulus PCMD was closely related to the structural and visual function parameters of glaucoma in both NTG and POAG. Furthermore, inner PCMD demonstrated a spatial correlation with corresponding RNFL thickness and VF MD.

To evaluate macular function and neural conduction along postretinal visual pathways in amblyopic patients. Twenty-five anisometropic amblyopic patients (mean age, 7 ± 1.9 years; visual acuity [VA]: 0.44 ± 0.27 logMAR in amblyopic [AM] eyes and 0.023 ± 0.067 logMAR in sound [SE] eyes) and 25 age-similar control subject ([CE] eyes, VA of 0.0 ± 0.0 logMAR in both eyes) were enrolled. In AM, SE, and CE eyes, simultaneous pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) were recorded in response to checks reversed at the rate of two reversals/second stimulating macular or extramacular areas (the check edge subtended 15 minutes and 60 minutes of visual arc, respectively). Nonsignificant differences (ANOVA, P > 0.005) were observed in PERG, in VEP responses to the 60-minute stimulus, and in retinocortical time with the 60-minute stimulus (RCT; the difference between VEP P100 and PERG P50 implicit times) between AM, SE, and CE eyes. AM eyes showed a significant (P < 0.005) increase in VEP P100 implicit time and in RCT in response to the 15-minute stimulus, compared with the values observed in SE and CE eyes. In AM patients, the interocular difference in VA was significantly (Pearson's test, P < 0.005) related to the interocular difference VEP P100 latencies and RCT with the 15-minute stimulus. Amblyopic eyes showed abnormal visual cortical responses only when the macular area was stimulated (increase in VEP P100 implicit times with the 15-minute stimulus). This functional impairment, in the presence of normal macular function (PERG responses similar to control eyes) may be attributable to a delay in postretinal neural conduction (increase in RCT).

Purpose: In primary open angle glaucoma (POAG) patients, elevated intraocular pressure usually leads to extracellular matrix remodeling and astrocytes activation. Thus, lamina cribrosa (LC) cells may play an important role in POAG progression. The objective of this study was to comprehensively explore gene expression profiles in LC cells of POAG patients.Materials and methods: Using the GSE13534 microarray datasets downloaded from Gene Expression Omnibus database, the differentially expressed genes (DEGs) between LC cells from POAG patients and controls were firstly screened based on the classical t-test and false discovery rate <0.05 as a significant threshold. Subsequently, these DEGs were grouped into gene sets using a graph-clustering approach. The underlying molecular mechanisms were investigated by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Results: A total of 57 DEGs were identified and 478 co-expression relationships were constructed among these DEGs. Among them, cytochrome p450 family 1 subfamily B (CYP1B1), brain-derived neurotrophic factor (BDNF) and myelin basic protein (MBP) showed high-degree relationships and they could interact with several genes. CYP1B1 is an important genetic gene involved in POAG and BDNF is an effective growth neurotrophic factor to weak POAG damage. MBP, versican (VCAN), integrin, alpha 4 (ITGA4) and N-cadherin (CDH2) may be involved in extracellular matrix remodeling in LC cells. FZD2 and FZD7 were enriched in basal cell carcinoma pathway.Conclusions: The results demonstrate that the genes above may be associated with the pathogenesis of POAG.

To compare the capability of the lamina cribrosa depth (LCD) and lamina cribrosa (LC) curvature in discriminating between eyes with primary open-angle glaucoma (POAG) and healthy eyes. Seventy-seven eyes of 77 patients with POAG and 77 eyes of 77 healthy subjects who were matched for age, sex, and axial length were included. The LCD and lamina cribrosa curvature index (LCCI) were measured in B-scan images obtained using swept-source optical coherence tomography at seven locations spaced equidistantly across the vertical optic disc diameter. The mean values of the measurements made at seven points of the LC were defined as the average LCD and LCCI. The average LCD (527.0 ± 116.4 vs. 413.3 ± 80.4 μm, P < 0.001) and average LCCI (10.97 ± 2.59 vs. 6.81 ± 1.43, P < 0.001) were significantly larger in POAG eyes than in the matched healthy subjects (all seven locations, P < 0.001). The area under the receiver operating characteristic curve (AUC) was significantly larger for the LCCI than the LCD (0.921 vs. 0.784, P < 0.001). The intraocular pressure was positively associated with average LCD and LCCI in healthy subjects (P = 0.021 and P < 0.001, respectively) and POAG patients (P = 0.011 and P < 0.001, respectively). Male sex was associated with larger average LCCI (P = 0.013) and LCD (P = 0.008) in POAG. The LCCI had significantly better discriminating capability between POAG and healthy eyes than LCD. This finding suggests that the LCCI may serve better than the LCD for improved glaucoma management.

Influence of Cataract Surgery on Optical Coherence Tomography and Neurophysiology Measurements in Patients With Retinitis Pigmentosa

Ocular hypertension (OHT), the common situation in adult patients in the outpatients, occurs ∼5% worldwide. However, there are still some practical problems in differentiation of OHT with early primary open-angle glaucoma (POAG) using current standard methods. Application of high resolution diffusion tensor imaging (DTI) enables us to the differentiate axonal architecture of visual pathway between POAG and OHT subjects. Among 32 POAG patients recruited (15 OHT and 14 control subjects), 62.5% of glaucoma were in early stage for the current study. All subjects underwent ophthalmological assessments with standard automated perimetry and optical coherence tomography (OCT). DTI was applied to measure fraction anisotropy (FA) and mean diffusivity (MD) of optic tract (OT), lateral geniculate body (LGN) and optic radiation (OR) using voxel-based analysis. Our data demonstrated that FA values of bilateral OR in POAG were significantly lower in the right or left than that of OHT patients (left OR: 0.51 ± 0.04 vs. 0.54 ± 0.03, p < 0.05; right OR: 0.51 ± 0.05 vs. 0.54 ± 0.03, p < 0.05). In right LGN, MD values were higher in POAG patients compared with OHT subjects (9.81 ± 1.45 vs. 8.23 ± 0.62, p < 0.05). However, no significant difference of all of the DTI parameters was observed between OHT and control subjects. DTI parameters in POAG patients were positively correlated with morphological and functional measurements (p < 0.05). Vertical cup to disc ratio (VCDR) was correlated with ipsilateral FA of OT (p < 0.05), ipsilateral MD of OT (p < 0.05), ipsilateral MD of LGN (p < 0.05), and contralateral MD of OT (p < 0.05). Mean deviation of visual field (MDVF) was correlated with ipsilateral FA of OT (p < 0.05), ipsilateral MD of OT (p < 0.05), and ipsilateral FA of LGN (p < 0.05). Our study demonstrated that DTI can differentiate POAG from OHT subjects in optic pathway, particularly in early POAG, and DTI parameters can quantify the progression of POAG.

To assess the association between the serum levels of uric acid (UA) and primary open-angle glaucoma (POAG). In this pilot study, 46 eyes of 23 patients with a clinical history of POAG and 30 eyes of 15 healthy subjects were included. All patients underwent a complete ophthalmological examination, including best corrected visual acuity (BCVA), intraocular pressure (IOP), and gonioscopy. Visual field parameters, such as mean deviation (MD) and pattern standard deviation (PSD), and optical coherence tomography (OCT) values of the optic nerve head, including retinal nerve fiber layer (RNFL) thickness and vertical cup/disc ratio (VCDR), were noted. A blood sample was collected from each subject for serum UA measurement. IOP, MD, PSD, RNFL thickness, and VCDR resulted significantly different in POAG patients, when compared with controls (p < 0.05). POAG patients showed significantly lower levels of mean serum UA than healthy controls (4.00 ± 0.66 mg/dL vs 4.95 ± 0.86 mg/dL, respectively, p < 0.0001). Furthermore, severe POAG patients showed mean serum levels of UA lower than mild POAG patients (3.36 ± 0.70 mg/dL vs 4.22 ± 0.51 mg/dL, respectively, p = 0.01). Visual field and OCT parameters were statistically correlated with the mean serum levels of UA in POAG eyes (p < 0.05). Results suggest that in POAG patients, serum UA levels may be decreased and correlated with visual field and OCT parameters worsening. Further larger multi-center prospective studies are necessary to confirm our findings and establish the role of UA in glaucoma.

Progression of Primary Open-Angle Glaucoma in Diabetic and Nondiabetic Patients

Background: Spectral-domain optical coherence tomography (OCT) can identify the presence of localized glaucomatous structural damage. The peripapillary retinal nerve fiber layer (RNFL) thickness is a popular OCT parameter used for glaucoma diagnosis and monitoring progression. Aim: To measure the peripapillary RNFL thickness, the pattern of RNFL defect, and association of RNFL with the severity of glaucoma using Spectralis Spectral Domain – OCT in patients with primary open-angle glaucoma (POAG) at a glaucoma clinic in a tertiary care teaching hospital in south India. Methods: Cross-sectional study design. Peripapillary RNFL thickness of 109 glaucomatous eyes of 56 patients aged 40–75 years having POAG, ocular hypertension, or suspected to have glaucoma but without visual field (VF) defects were included in the study. The cross-sectional thickness of RNFL using a 3.46 mm circle centered around the disc in 6 segments were measured and defects in the RNFL were identified by comparing measurements from each patient with the normative database. Results: The study included 109 eyes with 51 (46.79%) preperimetric eyes and 58 (53.21%) POAG eyes (with field defects). The average global thickness in the study population was 91.31 ± 12.81 µm for preperimetric eyes and 67.76 ± 17.33 µm for eyes with glaucoma. There was significant thinning in all segments between eyes with POAG and normal eyes with the mean difference highest in the inferotemporal segment (mean difference of 73.05) and the superotemporal segment (mean difference of 55.85). The global RNFL thickness had a coefficient of − 0.015 (standard error [SE] 0.003, 95% confidence interval [CI]: 0.02–0.009, R2 = 0.29) for mild glaucoma, −0.010 (SE 0.004, 95% CI: 0.02–0.003, R2 = 0.12) for moderate and − 0.18 (SE: 0.001, 95% CI: 0.022–0.014, R2 = 0.60) for severe glaucoma compared to preperimetric eyes in a linear regression model that adjusted for age and gender. Global and sector-wise RNFL thickness also had a significant area under Receiver Operator Characteristic (0.84, 95% CI: 0.78. 0.91) that showed the ability to discriminate between preperimetric and glaucomatous eyes. Possible “floor effect” of RNFL thickness was shown by 7 eyes with advanced glaucoma cases. Conclusion: RNFL thinning can be used as a parameter to assess glaucomatous structural loss that can aid in early diagnosis and monitoring of disease progression, to grade the severity of the disease in primary open-angle glaucoma, and when VFs cannot be done.