Purpose

To describe the location of initial visual field defects (VFD) in glaucoma, their modes of deterioration, and those factors associated with different modes of deterioration.

Methods

Patients with POAG were categorized into four groups based on three consecutive initial VFD: (1) superior paracentral defects (PD), (2) inferior PD, (3) superior nasal defects (ND), and (4) inferior ND. According to the worsening of the VF, four further subgroups were identified: (1) superior central worsening (CW), (2) inferior CW, (3) superior peripheral or nasal worsening (NW), and (4) inferior NW. Systemic and ocular factors were analyzed for each of the subgroups to identify possible associations.

Results

One hundred sixty-two eyes of 162 subjects were analyzed. Superior PD (n = 40) were more frequent in females and associated with disc hemorrhage (DH), and were less frequent in patients with systemic hypertension (HT). Inferior PD (n = 35) showed a significant association with cup shape measure and axial length. Superior ND (n = 37) were more highly associated with HT and diabetes. Inferior ND (n = 50) showed a lower incidence of DH. With binary logistic regression analysis, superior PD showed a significant association with both HT and DH. With respect to VF worsening, superior CW showed a significant association with HT and diabetes, whereas superior NW was associated with a high minimum IOP during follow-up, and inferior NW was associated with a high maximum IOP during follow-up.

Conclusions

The initial location and subsequent direction of worsening of VFD were associated with different systemic and ocular factors.

The present study evaluates the effect of celastrol on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). Celastrol, a quinine methide triterpene extracted from the perennial vine Tripterygium wilfordii (Celastraceae), has been identified as a potential neuroprotective candidate in a comprehensive drug screen against various neurodegenerative diseases. Two weeks after ONC, the average density of remaining RGCs in retinas of animals treated with daily intraperitoneal (i.p.) injections of celastrol (1mg/kg) was approximately 1332 cells/mm(2), or 40.8% of the Celastrol/Control group. In retinas of the Vehicle/ONC group about 381 RGCs/mm(2) were counted, which is 9.6% of the total number of RGCs in the DMSO/Control group. This corresponds to approximately a 250% increase in RGC survival mediated by celastrol treatment compared to Vehicle/ONC group. Furthermore, the average RGC number in retinas of ONC animals treated with a single intravitreal injection of 1mg/kg or 5mg/kg of celastrol was increased by approximately 80% (760 RGCs/mm(2)) and 78% (753 RGCs/mm(2)), respectively, compared to Vehicle/ONC controls (422 cells/mm(2)). Injection of 0.2mg/kg of celastrol had no significant effect on cell survival, with the average number of RGCs being 514 cells/mm(2) in celastrol-treated animals versus 422 cells/mm(2) in controls. The expression levels of Hsp70, Hsf1, Hsf2, HO-1 and TNF-alpha in the retina were analyzed to evaluate the roles of these proteins in the celastrol-mediated protection of injured RGCs. No statistically significant change in HO-1, Hsf1 and Hsp70 levels was seen in animals with ONC. An approximately 2 fold increase in Hsf2 level was observed in celastrol-treated animals with or without injury. Hsf2 level was also increased 1.8 fold in DMSO-treated animals with ONC injury compared to DMSO-treated animals with no injury suggesting that Hsf2 induction has an injury-induced component. Expression of TNF-alpha in retinas of celastrol-treated uninjured and ONC animals was reduced by approximately 2 and 1.5 fold compared to vehicle treated animals, respectively. The observed results suggest that mechanisms underlying celastrol׳s RGC protective effect are associated with inhibition of TNF-alpha-mediated cell death.

Nell2 is a neuron-specific protein containing six epidermal growth factor-like domains. We have identified Nell2 as a retinal ganglion cell (RGC)-expressed gene by comparing mRNA profiles of control and RGC-deficient rat retinas. The aim of this study was to analyze Nell2 expression in wild-type and optic nerve axotomized retinas and evaluate its potential role in RGCs. Nell2-positive in situ and immunohistochemical signals were localized to irregularly shaped cells in the ganglion cell layer (GCL) and colocalized with retrogradely-labeled RGCs. No Nell2-positive cells were detected in 2 weeks optic nerve transected (ONT) retinas characterized with approximately 90% RGC loss. RT-PCR analysis showed a dramatic decrease in the Nell2 mRNA level after ONT compared to the controls. Immunoblot analysis of the Nell2 expression in the retina revealed the presence of two proteins with approximate MW of 140 and 90 kDa representing glycosylated and non-glycosylated Nell2, respectively. Both products were almost undetectable in retinal protein extracts two weeks after ONT. Proteome analysis of Nell2-interacting proteins carried out with MALDI-TOF MS (MS) identified microtubule-actin crosslinking factor 1 (Macf1), known to be critical in CNS development. Strong Macf1 expression was observed in the inner plexiform layer and GCL where it was colocalizied with Thy-1 staining. Since Nell2 has been reported to increase neuronal survival of the hippocampus and cerebral cortex, we evaluated the effect of Nell2 overexpression on RGC survival. RGCs in the nasal retina were consistently more efficiently transfected than in other areas (49% vs. 13%; n = 5, p<0.05). In non-transfected or pEGFP-transfected ONT retinas, the loss of RGCs was approximately 90% compared to the untreated control. In the nasal region, Nell2 transfection led to the preservation of approximately 58% more cells damaged by axotomy compared to non-transfected (n = 5, p<0.01) or pEGFP-transfected controls (n = 5, p<0.01).

Prcis

Both macular superficial vessel density and ganglion cell complex (GCC) thickness measurement are significantly associated with regional and global 10-degree central visual field (VF) sensitivity in advanced glaucoma.

Purpose

The purpose of this study was to evaluate the regional and global structure-function relationships between macular vessel density (MVD) assessed by optical coherence tomography angiography (OCTA) and 10-2 VF sensitivity in advanced open angle glaucoma eyes.

Methods

Macular OCTA and 10-2 VF sensitivity of 44 patients [mean deviation (MD) <-10 dB] were evaluated. Regional and global VF mean sensitivity (MS) was calculated from total deviation plots. Superficial and deep MVD were obtained from 3 × 3 and 6×6 mm 2 OCTA scans using 2 sectoral definitions. Spectral-domain optical coherence tomography macular GCC thickness was obtained simultaneously from the same scan as the MVD measurements. Linear regression models were used to assess the associations ( R2 ).

Results

Lower MS was significantly associated with a reduction in superficial MVD and GCC in each region of both scan sizes for both maps. Associations were weaker in the individual sectors of the whole image grid than the Early Treatment Diabetic Retinopathy Study map. Deep-layer MVD was not associated with central MS. Although 6×6 mm 2 and perifoveal vessel density had better associations with central 10-degree MS compared with GCC thickness (eg, R2 from 25.7 to 48.1 µm and 7.8% to 32.5%, respectively), GCC associations were stronger than MVD associations in the central 5-degree MS.

Conclusions

Given a stronger MVD-central 10-degree VF association compared with GCC, as well as stronger GCC-central 5-degree VF association compared with MVD, MVD and GCC are complementary measurements in eyes with advanced glaucoma. A longitudinal analysis is needed to determine the relative utility of the GCC and MVD measurements.