Retinal Neurodegeneration in an Intraocular Pressure Fluctuation Rat Model.

Increased intraocular pressure (IOP) is the most important risk factor for glaucoma. The role of IOP fluctuation, independently from elevated IOP, has not yet been confirmed in glaucoma. We investigated the effects of IOP fluctuation itself on retinal neurodegeneration. Male rats were treated with IOP-lowering eyedrops (brinzolamide and latanoprost) on Mondays and Thursdays (in the irregular instillation group) or daily (in the regular instillation group), and saline was administered daily in the normal control group for 8 weeks. The IOP standard deviation was higher in the irregular instillation group than the regular instillation group or the control group. The degree of oxidative stress, which was analyzed by labeling superoxide, oxidative DNA damage, and nitrotyrosine, was increased in the irregular instillation group. Macroglial activation, expressed by glial fibrillary acidic protein in the optic nerve head and retina, was observed with the irregular instillation of IOP-lowering eyedrops. Microglial activation, as indicated by Iba-1, and the expression of TNF-α did not show a significant difference between the irregular instillation and control groups. Expression of cleaved caspase-3 was upregulated and the number of retinal ganglion cells (RGCs) was decreased in the irregular instillation group. Our findings indicate that IOP fluctuations could be induced by irregular instillation of IOP-lowering eyedrops and this could lead to the degeneration of RGCs, probably through increased oxidative stress and macrogliosis.

Glaucoma diagnostic ability of ganglion cell-inner plexiform layer thickness differs according to the location of visual field loss.

OBJECTIVE: To determine whether the ganglion cell-inner plexiform layer (GCIPL) or circumpapillary retinal nerve fiber layer (cpRNFL) is better at distinguishing eyes with early glaucoma from normal eyes on the basis of the the initial location of the visual field (VF) damage. DESIGN: Retrospective, observational study. PARTICIPANTS: Eighty-four patients with early glaucoma and 43 normal subjects were enrolled. The patients with glaucoma were subdivided into 2 groups according to the location of VF damage: (1) an isolated parafoveal scotoma (PFS, N = 42) within 12 points of a central 10 degrees in 1 hemifield or (2) an isolated peripheral nasal step (PNS, N = 42) within the nasal periphery outside 10 degrees of fixation in 1 hemifield. METHODS: All patients underwent macular and optic disc scanning using Cirrus high-definition optical coherence tomography (Carl Zeiss Meditec, Dublin, CA). The GCIPL and cpRNFL thicknesses were compared between groups. Areas under the receiver operating characteristic curves (AUCs) were calculated. MAIN OUTCOME MEASURES: Comparison of diagnostic ability using AUCs. RESULTS: The average and minimum GCIPL of the PFS group were significantly thinner than those of the PNS group, whereas there was no significant difference in the average retinal nerve fiber layer (RNFL) thickness between the 2 groups. The AUCs of the average (0.962) and minimum GCIPL (0.973) thicknesses did not differ from that of the average RNFL thickness (0.972) for discriminating glaucomatous changes between normal and all glaucoma eyes (P =0.566 and 0.974, respectively). In the PFS group, the AUCs of the average (0.988) and minimum GCIPL (0.999) thicknesses were greater than that of the average RNFL thickness (0.961, P =0.307 and 0.125, respectively). However, the AUCs of the average (0.936) and minimum GCIPL (0.947) thicknesses were lower than that of the average RNFL thickness (0.984) in the PNS group (P =0.032 and 0.069, respectively). CONCLUSIONS: The GCIPL parameters were more valuable than the cpRNFL parameters for detecting glaucoma in eyes with parafoveal VF loss, and the cpRNFL parameters were better than the GCIPL parameters for detecting glaucoma in eyes with peripheral VF loss. Clinicians should know that the diagnostic capability of macular GCIPL parameters depends largely on the location of the VF loss.

The Relationship between Myopia and Obesity in Adults.

PURPOSE: To investigate the relationship between myopia and obesity through direct measurements of fat content. METHODS: A cross-sectional study used a stratified, multistage survey, the Korea National Health and Nutrition Examination Survey (2008-2010). Subjects 19 years or older (n = 10,305) were included. Participants were divided into three groups according to refractive status: myopia (spherical equivalent [SE] ≤ -1.0 diopter [D]), emmetropia (-1.0 D < SE ≤ 1.0 D), and hyperopia (SE > 1.0 D). Obesity was investigated with assessment of fat mass and body mass index or waist circumference. Fat mass was measured with whole-body dual energy x-ray absorptiometry. Body fat percentage was calculated as (total fat mass / body weight × 100). RESULTS: Higher obesity index was found in individuals with myopic eyes after adjustment for age, sex, education level, income status, physical activity, residence, and serum vitamin D level. The significant difference in total body fat percentages among myopia, emmetropia, and hyperopia was significant in the young age group (19-39 years, p < 0.05) but not in the middle age group (40-64 years) and the old age group (≥65 years). Individuals with a higher percentage of total body fat had greater odds ratios for myopia (fourth quartile of body fat; odds ratio, 1.352; 95% confidence interval, 1.178-1.551). CONCLUSIONS: An association was found between adiposity and myopia in relatively young adults using direct measurements of fat mass.

Exploring Neuroprotective Effects of Topical Brimonidine in Experimental Diabetic Retinopathy.

BACKGROUND/AIM: Diabetic retinopathy is a leading cause of blindness worldwide, characterized by neurovascular dysfunction. This study aimed to investigate the impact of brimonidine, a selective adrenoceptor agonist, on diabetic retinal neurodegeneration, recognizing the critical role of neurodegeneration in diabetic retinopathy. MATERIALS AND METHODS: Streptozotocin-induced diabetes was established in adult male Sprague-Dawley rats to mimic diabetic retinopathy. Rats, except non-diabetic control rats, received topical applications of 0.15% brimonidine tartrate (treatment group) or balanced salt solution (diabetic control group) twice daily following diabetes induction. Each group comprised six randomly assigned animals. Retinal samples were analyzed using immunofluorescence staining, apoptosis assay, and western blot. RESULTS: Topical brimonidine treatment reduced apoptosis of retinal ganglion cells at 8 weeks after induction of diabetes (p<0.05). Glial activation induced by diabetes was reduced by brimonidine treatment. Immunoblot and immunofluorescence assay revealed that the decrease in phospho- protein kinase B (AKT) level resulting from diabetes was also attenuated by brimonidine (p<0.05). Furthermore, brimonidine alleviated the decrease in anti-apoptotic proteins [BCL2 apoptosis regulator (BCL2) and BCL-xl] induced by diabetes (p<0.05). Elevation of phospho-p38 mitogen-activated protein kinase (p38MAPK) and p53 in diabetic rats were reduced by brimonidine (p<0.05). Additionally, brimonidine treatment attenuated the upregulation of the pro-apoptotic molecule BCL-2 associated X in retinas of diabetic rats (p<0.05). CONCLUSION: These findings suggest that topical brimonidine treatment may protect retinal ganglion cells in experimental diabetes by modulating the AKT pathway and reducing pro-apoptotic p38MAPK levels. This presents a potential neuroprotective approach in diabetes, offering the advantage of localized treatment without the added burden of oral medication.

Long-Term Intraocular Pressure Fluctuation and Epiretinal Membrane in Patients with Glaucoma or Glaucoma Suspect.

Background: A relationship between glaucoma and epiretinal membrane (ERM) has been suggested previously. We investigated the association between intraocular pressure (IOP) fluctuation and idiopathic ERM in patients with glaucoma or glaucoma suspect. Methods: Among patients with glaucoma or glaucoma suspect, data from 43 patients with ERM and 41 patients without ERM were reviewed and analyzed in this retrospective study. The long-term fluctuation of IOP was defined based on the standard deviation of IOP across all visits. Results: Patients with ERM were older and had a higher SD of IOP and a higher proportion of having a history of cataract surgery and greater macular thickness (p = 0.018, 0.049, 0.013, and <0.001, respectively). In multiple logistic regression analysis, the high-IOP-fluctuation group was associated with the presence of ERM (p = 0.047). Among patients with ERM, eyes with stage-3 or -4 ERM had worse visual field defects based on mean deviation than those with stage-1 or -2 ERM (p = 0.025). Conclusions: Long-term IOP fluctuation was associated with idiopathic ERM in patients with glaucoma or glaucoma suspect. Idiopathic ERM could serve as a biomarker for long-term IOP fluctuation in glaucoma patients, particularly in clinics where measuring long-term IOP fluctuation during the first visit is not feasible due to its time-consuming nature.

Parallel Analysis of Exosomes and Cytokines in Aqueous Humor Samples to Evaluate Biomarkers for Glaucoma.

Recent emerging studies have demonstrated numerous critical roles of exosomes in cell-to-cell signaling. We investigated exosomes in the aqueous humor of glaucoma patients and controls and compared their characteristics with other biomarkers such as cytokines. Glaucoma patients exhibited higher exosome particle counts and smaller sizes compared to controls. Higher exosome density was correlated with more severe visual field loss. Conversely, concentrations of aqueous humor cytokines, particularly PD-L1, were primarily associated with intraocular pressure, and none of the cytokines showed a significant association with visual field damage. This may reflect the characteristics of exosomes, which are advantageous for crossing various biological barriers. Exosomes may contain more information about glaucoma functional damage occurring in the retina or optic nerve head. This highlights the potential importance of exosomes as signaling mediators distinct from other existing molecules.

Thicker Inner Nuclear Layer as a Predictor of Glaucoma Progression and the Impact of Intraocular Pressure Fluctuation.

Background: Thickening of the inner nuclear layer (INL) or microcystic macular changes has been reported to be implicated in glaucoma patients, but their potential impact on disease progression remains unclear. We investigated the relationship between baseline microcystic macular edema in the INL or INL thickness and subsequent visual field (VF) progression in glaucoma patients. Methods: This retrospective observational study included primary open-angle glaucoma with follow-up exceeding 3 years. We identified macular cystic changes through Spectralis optical coherence tomography and measured the INL thickness using automated segmentation. Glaucoma progression was determined using the Guided Progression Analysis program of the Humphrey filed analyzer, calculating the mean deviation (MD) changes (dB/year). Results: Microcystic macular changes were observed in 12 (7.5%) of 162 patients. Patients with microcystic macular change had thicker INL thickness than those without it (p = 0.010). Progressors had a higher probability of having microcystic macular changes and a thicker average INL thickness than nonprogressors (p = 0.003, p = 0.019). Thicker INL thickness was associated with faster VF progression based on MD slope (dB/year) in the multivariate regression analysis (p = 0.045). Additionally, greater intraocular pressure (IOP) fluctuation was found to be associated with both a thicker INL and the presence of microcystic changes in the multivariate regression analysis (p = 0.003, 0.028). Conclusions: Increased macular INL thickness indicative of INL changes was linked to subsequent VF progression in glaucoma patients. These findings suggest that retinal inner nuclear change could serve as an indicator of progressive glaucoma.

Neuroprotective effects of cilostazol on retinal ganglion cell damage in diabetic rats.

Neurodegeneration is an important component of diabetic retinopathy, with increasing evidence that retinal ganglion cell (RGC) death occurs early in diabetes. We investigated the effects of cilostazol, which has been widely used to manage diabetic complications, on retinal ganglion cell death in the diabetic retina. Four-week-old Otsuka Long-Evans Tokushima fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats as matched nondiabetic controls were treated with daily oral cilostazol at 30 mg/kg or 0.9% saline solution. In OLETF rats at the age of 40 weeks, glial fibrillary acidic protein (GFAP) immunofluorescence staining was upregulated in vertical sections, and showed a more ramified pattern in whole-mount retinas compared with that in LETO rats. Vascular endothelial growth factor (VEGF) expression was limited to the ganglion cell layer in LETO rats, but extended into the outer plexiform layer in OLETF rats. Immunofluorescence staining and Western blotting demonstrated that cilostazol treatment reduced GFAP and VEGF expression in the retinas of OLETF rats. Terminal deoxynucleotidyl transferase-mediated terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling (TUNEL) staining revealed an increase in the RGC layer in OLETF compared with LETO rats (P < 0.05), and cilostazol treatment reduced the number of TUNEL-positive cells in OLETF rats (P < 0.05). Relieving retinal ischemia by systemic cilostazol treatment had a noticeable protective effect on RGCs in diabetic rats. Cilostazol treatment may be useful for the management of diabetic retinal vascular dysfunction and neuronal degeneration.

Visualization of blebs using anterior-segment optical coherence tomography after glaucoma drainage implant surgery.

OBJECTIVE: The current study investigated the internal structure of blebs using anterior-segment optical coherence tomography (AS-OCT) in patients who had undergone Ahmed glaucoma valve (AGV) (New World Medical Inc, Rancho Cucamonga, CA) implantation and compared the differences between successful and failed surgeries. DESIGN: Cross-sectional, observational study. PARTICIPANTS: A total of 76 patients who had undergone AGV implantation. METHODS: The blebs after AGV implantation were examined using AS-OCT. The relationship between intraocular pressure (IOP) or the number of glaucoma medications and intrableb parameters was evaluated. Success was defined as IOP ≤ 21 mmHg with a maximum of 2 glaucoma medications, and the remaining cases were assigned to the "failed surgery group." Logistic regression was used to determine the predictive value of various bleb parameters measured by AS-OCT for bleb success. MAIN OUTCOME MEASURES: The bleb wall thickness (minimum and maximum) and the reflectivity of the bleb wall (mean, modal value, minimum, and maximum). RESULTS: Blebs from 46 successful (60.5%) and 30 failed (39.5%) AGV implantation surgeries were analyzed. The AS-OCT imaging of the intrableb configuration revealed a relatively regular surface and a homogeneous and hyperreflective bleb wall. The maximum and minimum bleb wall thicknesses were significantly different between the 2 groups (P<0.001, P<0.005). No significant differences were observed between the 2 groups in mean, modal, maximum, or minimum reflectivity of the bleb wall. The maximum and minimum bleb wall thicknesses were significantly correlated with the postoperative maximum IOP (r = 0.402, P<0.001; r = 0.280, P = 0.014). The maximum and minimum bleb wall thicknesses showed a significant correlation with the number of postoperative glaucoma eye drops (r = 0.452, P<0.001; r = 0.327, P = 0.004). Maximum bleb wall thickness was significantly associated with the success of AGV surgery by multivariate analysis (P<0.001). CONCLUSIONS: Anterior-segment OCT can be used for bleb imaging after glaucoma valve implantation. The AS-OCT results revealed that the maximum bleb wall was significantly thinner in successful AGV implant surgeries compared with unsuccessful AGV implant surgeries. This technique may facilitate the investigation of surgical outcomes and pathogenesis in patients receiving glaucoma valve implants. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Cytokines Associated With Onset of a Hypertensive Phase and Surgical Failure After Ahmed Glaucoma Valve Implantation.

PURPOSE: To investigate the relationship between cytokines of the aqueous humor or Tenon capsule, the onset of a hypertensive phase, and surgical failure in patients undergoing Ahmed Glaucoma Valve (AGV) implantation DESIGN: Prospective clinical cohort study. METHODS: A total of 36 patients who underwent AGV implantation were included. Samples of aqueous humor and Tenon tissue were collected at the time of surgery. Multiple cytokines were evaluated in the samples using a bead-based multiplex cytokine assay. As for surgical outcomes, a hypertensive phase was defined as an intraocular pressure (IOP) of greater than 21 mm Hg within 3 months after surgery, whereas surgical failure was defined as an IOP greater than 21 mm Hg with maximum tolerable glaucoma medications during 2 consecutive visits. RESULTS: Patients who entered a hypertensive phase showed higher transforming growth factor-ß2 (TGF-ß2) levels in the aqueous humor (P = .012). A longer axial length and higher TGF-ß2 concentration of the aqueous humor were associated with higher maximum IOP values during 3 months after surgery per multiple regression analysis (P = .028 and P = .034). In the multiple logistic regression analysis, higher monocyte chemoattractant protein-1 (MCP-1) concentrations in the aqueous humor and higher interleukin-4 concentrations in Tenon tissue were related to surgical failure (P = .022 and P = .040). CONCLUSIONS: Greater concentrations of TGF-ß2 and MCP-1 were related to surgical outcome after glaucoma drainage device implantation. Further studies are needed to confirm that down-regulation of these cytokines could be helpful in improving surgical outcomes.

Normotensive Glaucoma in the Fellow Eye of Patient with Unilateral Pseudoexfoliation.

PURPOSE: To investigate the characteristics of normotensive glaucoma (NTG) in the fellow eye of patients with unilateral pseudoexfoliation syndrome (PXS). METHODS: This study is a retrospective chart review. We included 313 patients with NTG. Using the 1:1 matched propensity score, only 94 well-matched patients were selected. A total of 47 NTG patients who had PXS in their contralateral eye (PXS group) and 47 NTG patients who did not (control group) were compared. The propensity score was matched based on age, mean intraocular pressure (IOP), baseline retinal nerve fiber layer (RNFL) thickness and baseline mean deviation (MD) of visual field (VF) score. The diagnosis of NTG was based on the presence of glaucomatous optic nerve head injury with VF defect, intraocular pressure less than 22 mmHg, open angles and no pseudoexfoliation material. RESULTS: The PXS group had a higher ratio of males (34.0%) than the control group (17.0%). No significant differences were observed between the two groups in terms of CCT, axial length, untreated baseline IOP, baseline PSD of VF, systemic blood pressure and follow-up duration. The rate of RNFL thinning was significantly faster in the PXS group (-1.88 ± 2.83 µm/year) compared with the control group (-0.27 ± 5.29 µm/year) (p = 0.02). The progression rate of VF MD was slightly faster in PXS than in the control group, but there was no statistically significant difference (PXS group, -0.33 ± 0.90 dB/year; control group, -0.11 ± 0.84 dB/year; p = 0.236). CONCLUSIONS: NTG eyes with PXS showed faster RNFL thinning than did control NTG eyes.

Effect of a Pericardium Graft Inserted Adjacent to the Endplate in the Ahmed Glaucoma Valve Implantation.

The surface area of encapsulation around the Ahmed glaucoma valve (AGV) endplate is a critical factor in the surgical outcome as it is associated with the degree of IOP reduction. We investigated the surgical outcome of AGV implantation with an additional pericardium graft inserted adjacent to the endplate, with the intent of expanding the surface area of encapsulation. We enrolled 92 patients (92 eyes) who underwent AGV implantation. Of them, 50 patients underwent conventional surgery (termed the without-expansion group), and 42 received an additional an 8 × 6 mm pericardium graft inserted adjacent to the AGV endplate at the sub-Tenon's space (with-expansion). The hypertensive phase was classified as mild (>21 mmHg), moderate (>25 mmHg), and severe (>30 mmHg). Six months post-surgery, the with-expansion group exhibited a lower IOP (14.90 ± 4.27 mmHg) and lower peak IOP (22.29 ± 4.95 mmHg) than the without-expansion group (17.56 ± 4.88 mmHg and 25.06 ± 6.18 mmHg, p = 0.008 and p = 0.021, respectively). The with-expansion group exhibited a relatively low rate of moderate (16.7%) and severe (4.8%) hypertensive phases compared to the without-expansion group (40.0% and 20.0%, with p = 0.014 and p = 0.031, respectively). The additional pericardium graft was associated with a reduced occurrence of moderate hypertensive phase in both univariate and multivariate analysis logistic regression analyses (p = 0.017 and p = 0.038, respectively). Endplate surface area expansion using an additional pericardium graft reduced the occurrence of moderate and severe hypertensive phases, and lower postoperative 6-month IOP could be achieved.

Attenuated Amplitude of Pattern Electroretinogram in Glaucoma Patients with Choroidal Parapapillary Microvasculature Dropout.

This study aims to investigate whether parapapillary choroidal microvasculature dropout (MvD) is related to visual function measured by pattern electroretinogram (PERG) in glaucomatous eyes with ß-zone parapapillary atrophy (PPA). A total of 79 patients with open angle glaucoma and preperimetric glaucoma with ß-zone PPA was included in this cross-sectional study. Through the deep layer of the Swept-source optical coherence tomography angiography image, the angular width and the area of MvD were measured. Visual function was evaluated with a standard automated perimetry and PERG. N95 and P50 PERG amplitudes in eyes with MvD were noticeably decreased compared to those without MvD (p = 0.004 and p = 0.007, respectively), although the mean deviation was not significantly different (p = 0.107). The lower N95 amplitude was associated with the presence of MvD (ß = -0.668, p = 0.017) and wider angular width of MvD (B = -7.612, p = 0.014). Old age (p = 0.001), average ganglion cell's inner plexiform layer thickness (p = 0.003), and the presence of MvD (p = 0.020) were significantly related to low N95 amplitude. Association between the presence and extent of the MvD and PERG amplitudes suggests that the presence of MvD has relevance to the generalized dysfunction of retinal ganglion cells.

Neuroprotective Effects of Nicotinamide (Vitamin B3) on Neurodegeneration in Diabetic Rat Retinas.

The loss of inner retinal neurons is an initial event in diabetic retinopathy. In diabetic retinas, oxidative stress is increased, which could lead to increased oxidative DNA damage. Nicotinamide is a precursor to nicotinamide adenine dinucleotide, which contributes to the DNA damage response. We investigated whether nicotinamide plays a neuroprotective role in diabetic retinal neurodegeneration in terms of DNA repair. Male Sprague Dawley rats with streptozotocin-induced diabetes were orally administered nicotinamide (500 mg/kg/day) for 4 or 12 weeks. Oxidative stress exhibited by dihydroethidium was upregulated at 4 and 12 weeks after onset of diabetes, and nicotinamide treatment reduced oxidative stress at 4 weeks after induction of diabetes. Oxidative DNA damage measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG) increased at 4 and 12 weeks after induction of diabetes and decreased following nicotinamide treatment. The elevated expression of glial fibrillary acidic protein (GFAP) induced by diabetes was attenuated by nicotinamide treatment. In Western blot analysis, the increased expression of cleaved PARP-1 in diabetes was attenuated by nicotinamide treatment at 12 weeks after induction of diabetes. The diabetes-induced apoptosis of inner retinal cells detected by the TUNEL assay was reduced by nicotinamide treatment. In conclusion, nicotinamide attenuated retinal neurodegeneration in diabetes, probably by reducing oxidative DNA damage and supporting DNA repair.

Macular Blood Flow and Pattern Electroretinogram in Normal Tension Glaucoma.

PURPOSE: To investigate whether macular vessel density (VD) was associated with the pattern electroretinogram (PERG) in normal tension glaucoma (NTG). DESIGN: Cross-sectional study. METHODS: Seventy-six eyes from patients with NTG were included in this study. Macular VD was calculated from the superficial retinal layer, including the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), using the built-in software provided with the optical coherence tomography angiography (OCTA) device. Functional parameters were obtained from standard automated perimetry (SAP) and PERG, using a commercial ERG stimulator. Moreover, structural parameters, such as peripapillary RNFL and macular ganglion cell/inner plexiform layer (GCIPL) thickness, were measured using OCT. RESULTS: Patients with higher VD had higher N95 amplitude (p = 0.048). Macular VD was significantly correlated with N95 amplitude, irrespective of disease severity (r = 0.352, p = 0.002 for the total subjects and r = 0.276, p = 0.043 for mild glaucoma). According to regression analyses, N95 amplitude and macular VD were bidirectional significant factors (p = 0.035 and 0.019, respectively). For patients with mild to moderate glaucoma, N95 amplitude and macular VD were also significantly associated bidirectionally, according to regression analyses (p = 0.032 and 0.040, respectively). CONCLUSIONS: Macular VD was significantly associated with N95 amplitude from PERG. The correlation was prominent in early glaucoma, in contrast to the other structural or functional parameters. When considering that PERG represents the objective function of the retinal ganglion cell (RGC), macular VD was associated with RGC dysfunction before the functional change became apparent on SAP.

Intereye structure-function relationship using photopic negative response in patients with glaucoma or glaucoma suspect.

We evaluated the intereye structure-function relationship in glaucoma patients using photopic negative response in electroretinogram analysis. Patients with confirmed glaucoma (36 eyes, 36 patients) or suspected glaucoma (19 eyes, 19 patients) were included in this study. Electroretinogram (RETI-scan) was performed with red stimulus on blue background. Intereye comparison for 55 patients was performed between better eyes and worse eyes, which were divided based on average retinal nerve fiber layer (RNFL) thickness measured using spectral-domain optical coherence tomography. In the intereye analysis, PhNR amplitude was lower in worse eyes than in better eyes (P < 0.001). The intereye difference in PhNR amplitude was significantly correlated with intereye difference in average RNFL, as well as average or minimum ganglion cell-inner plexiform layer (GCIPL) thickness (P = 0.006, 0.044, 0.001). In patients with mean deviation ≥ - 6 dB of worse eyes, the intereye difference in PhNR amplitude was significantly associated with intereye difference in average RNFL thickness or minimum GCIPL thickness (P = 0.037, 0.007), but significant correlation was not found between mean sensitivity of visual field tests and structural parameters. In conclusion, PhNR performed well with regard to intereye structure-function association in glaucoma patients, especially at the early stage.

Characteristics of progressive temporal visual field defects in patients with myopia.

Temporal visual field damage (VFD) is the common type of non-glaucomatous VF defects found in eyes with myopia. However, little is known about the factors associated with its progression. We investigated the characteristic of myopic eyes with progressive temporal VF defects. This retrospective, observational study included a total of 116 eyes: 39 eyes with temporal VFDs and an axial length greater than 24.5 mm, 77 eyes with typical glaucomatous VFDs who were followed up more than 5 years. VF progression was evaluated with Trend-based global progression analysis. In the temporal VFD group, the greater tilt ratios, the higher prevalence of ß-zone peripapillary atrophy (ß-PPA), the substantial increase in ß-PPA were found, compared to the typical glaucomatous VFD groups (all P-values ≤ 0.001). The temporal VFD group had the slower progression than the typical glaucomatous VFD group on trend-based GPA (P = 0.047). In the multivariate linear regression analysis, the change of ß-PPA area over years was related to temporal VFD progression (B, - 0.000088, P = 0.003). In conclusion, myopic eyes with the temporal VFD, which come with growing ß-PPA area, should be monitored with extra caution.

Simultaneously performed combined 24-2 and 10-2 visual field tests in glaucoma.

Using either 24-2 or 10-2 visual field (VF) testing only is not enough to cover all the various types of glaucomatous VF defects. We investigated the performance of the combined 24-2 and 10-2 perimetry when conducted together and separately using the structure-function relationship. A total of 30 glaucoma patients with isolated peripheral nasal step, 37 patients with isolated paracentral scotoma, and 38 patients with both paracentral and nasal scotoma were included. To create the combined Humphrey VF test, a custom test pattern was established using the built-in custom point options, an example of the X, Y coordinate system. In glaucoma patients with peripheral nasal step, the superotemporal topographic structure-function relationship with peripapillary retinal nerve fiber layer (RNFL) thickness was superior in relation to the combined or 24-2 perimetry relative to the 10-2 perimetry (both P < 0.05). The combined VF test showed more favorable inferotemporal or inferonasal structure-function correlation with the corresponding ganglion cell-inner plexiform layer (GCIPL) thickness when compared with results gleaned using the 24-2 VF test (P < 0.05). Simultaneously performed 24-2 and 10-2 VF tests demonstrated a superior topographic structure-function relationship when compared with them separately performed in some sectors.

The effect of anxiety and depression on progression of glaucoma.

Glaucoma is considered a chronic disease that requires lifelong management. Chronic diseases are known to be highly associated with psychological disturbances such as depression and anxiety. There have also been many studies on association between anxiety or depression and glaucoma. The majority of these studies explained that the glaucoma diagnosis causes anxiety or depression. However, It is also necessary to evaluate whether the psychological disturbance itself affect glaucoma. Therefore, we investigated the association of anxiety and depression with glaucoma progression, and elucidate mechanisms underlying that. We included 251 eyes with open angle glaucoma who were followed up for at least 2 years in this retrospective case-control study. The Beck Anxiety Inventory (BAI) and Beck Depressive Inventory-II (BDI-II) were used to assess anxiety and depression in glaucoma patients. Patients were classified into groups (high-anxiety group; HA-G, low-anxiety group; LA-G, high-depression group; HD-G, low-depression group; LD-G) according to their score on the BAI or BDI-II (separately). In logistic regression analysis, disc hemorrhage, peak intraocular pressure (IOP) and RNFL thickness loss rate were significantly associated with high anxiety (p = 0.017, p = 0.046, p = 0.026). RNFL thinning rate and disc hemorrhage were significant factors associated with anxiety in multivariate models (p = 0.015, p = 0.019). Multivariate linear regression analysis showed a significant positive correlation between the rate of RNFL thickness loss and BAI score (B = 0.058; 95% confidential interval = 0.020-0.097; p = 0.003), and RNFL loss and IOP fluctuation (B = 0.092; 95% confidential interval = 0.030-0.154; p = 0.004). For the depression scale, visual field mean deviation and heart rate variability were significantly associated with high depression in multivariate logistic regression analysis (p = 0.003, p = 0.006). We suggest that anxiety increase the risk of glaucoma progression and they are also associated with IOP profile and disc hemorrhage.

Predicting the development of normal tension glaucoma and related risk factors in normal tension glaucoma suspects.

This study investigated the predicted risk factors for the development of normal-tension glaucoma (NTG) in NTG suspects. A total of 684 eyes of 379 NTG suspects who were followed-up for at least 5 years were included in the study. NTG suspects were those having (1) intraocular pressure within normal range, (2) suspicious optic disc (neuroretinal rim thinning) or enlarged cup-to-disc ratio (≥ 0.6), but without definite localized retinal nerve fiber layer (RNFL) defects on red-free disc/fundus photographs, and (3) normal visual field (VF). Demographic, systemic, and ocular characteristics were determined at the time of the first visit via detailed history-taking and examination of past medical records. Various ocular parameters were assess using spectral-domain optical coherence tomography and Heidelberg retinal tomography. Conversion to NTG was defined either by the presence of a new localized RNFL defect at the superotemporal or inferotemporal region on disc/fundus red-free photographs, or presence of a glaucomatous VF defect on pattern standard deviation plots on two consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. In total, 86 (12.6%) of the 684 NTG suspects converted to NTG during the follow-up period of 69.39 ± 7.77 months. Significant (P < 0.05, Cox regression) risk factors included medication for systemic hypertension, longer axial length, worse baseline VF parameters, thinner baseline peripapillary RNFL, greater disc torsion, and lamina cribrosa (LC) thickness < 180.5 µm (using a cut-off value obtained by regression analysis). Significant (P < 0.05, Cox regression) risk factors in the non-myopic NTG suspects included medication for systemic hypertension and a LC thinner than the cut-off value. Significant (P < 0.05, Cox regression) risk factors in the myopic NTG suspects included greater disc torsion. The results indicated that 12.6% of NTG suspects converted to NTG during the 5-6-year follow-up period. NTG suspects taking medication for systemic hypertension, disc torsion of the optic disc in the inferotemporal direction, and thinner LC of the optic nerve head at baseline were at greater risk of NTG conversion. Related baseline risk factors were different between myopic and non-myopic NTG suspects.