Sector-specific Association of Intraocular Pressure Dynamics in Dark-room Prone Testing and Visual Field Defect Progression in Glaucoma.

PURPOSE: To investigate sectoral differences in the relationship between intraocular pressure (IOP) dynamics during dark-room prone testing (DRPT) and visual field (VF) defect progression in primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective, longitudinal study. PARTICIPANTS: This retrospective study included 116 eyes of 84 POAG patients who underwent DRPT and had at least 5 reliable VF tests conducted over a more than 2-year follow-up period. We excluded eyes with mean deviation worse than -20 dB or a history of intraocular surgery or laser treatment. METHODS: Average total deviation (TD) was calculated in the superior, central, and inferior sectors of the Humphrey 24-2 or 30-2 program. During DRPT, IOP was measured in the sitting position, and after 60 minutes in the prone position in a dark room, IOP was measured again. The relationship between IOP change during DRPT, IOP after DRPT, and TD slope in each quadrant was analyzed with a linear mixed-effects model, adjusting for other potential confounding factors. MAIN OUTCOME MEASURES: Total deviation slope in each quadrant, IOP change during DRPT, and IOP after DRPT. RESULTS: Intraocular pressure after DRPT and IOP change during DRPT were 18.16 ± 3.42 mmHg and 4.92 ± 3.12 mmHg, respectively. Superior TD slope was significantly associated with both IOP after DRPT (ß = -0.28, P = 0.003) and IOP change during DRPT (ß = -0.21, P = 0.029), while central (ß = -0.05, P = 0.595; ß = -0.05; P = 0.622) and inferior (ß = 0.05, P = 0.611; ß = 0.01, P = 0.938) TD slopes were not. CONCLUSION: Dark-room prone testing might be a useful test to predict the risk of superior VF defect progression in eyes with POAG. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The association between intraocular pressure dynamics during dark-room prone testing and intraocular pressure over a relatively long-term follow-up period in primary open-glaucoma patients.

PURPOSE: To investigate the relationship between the dynamics of intraocular pressure (IOP) during dark-room prone testing (DRPT) and IOP over a relatively long-term follow-up period. METHODS: This retrospective study enrolled 84 eyes of 51 primary open-angle glaucoma patients who underwent DRPT for whom at least three IOP measurements made using Goldmann applanation tonometry were available over a maximum follow-up period of two years. We excluded eyes with a history of intraocular surgery or laser treatment and those with changes in topical anti-glaucoma medication during the follow-up period. In DRPT, IOP was measured in the sitting position, and after 60 min in the prone position in a dark room, IOP was measured again. In this study, IOP fluctuation refers to the standard deviation (SD) of IOP, and IOP max indicates the maximum value of IOP during the follow-up. The relationship between these parameters was analyzed with a linear mixed-effects model, adjusting for clinical parameters including age, gender, and axial length. RESULTS: IOP increased after DRPT with a mean of 6.13 ± 3.55 mmHg. IOP max was significantly associated with IOP after DRPT (ß = 0.38; p < 0.001). IOP fluctuation was significantly associated with IOP change in DRPT (ß = 0.29; p = 0.007). CONCLUSION: Our findings suggest that short-term and relatively long-term IOP dynamics are associated. Long-term IOP dynamics can be predicted by DRPT to some extent.

Factors Affecting the Second Complete Atypical Femoral Fracture after the First Atypical Fracture.

OBJECTIVES: Atypical femoral fracture (AFF) is an atypical low-energy subtrochanteric and diaphyseal femoral fracture. Even if bone fusion is achieved in patients with AFF, the risk of AFF in the contralateral femur must be considered. This study aimed to investigate the factors affecting complete AFF in the contralateral femur and conservatively treated incomplete AFF. SUBJECT AND METHODS: Radiographs of 111 femurs in 104 AFF cases were examined, and the femurs were classified as follows: 85 contralateral femurs with complete AFF; 18 contralateral femurs with incomplete AFF; 8 femurs with incomplete AFF without surgical treatment. Various patients' clinical data were collected, and we investigated the factors affecting the second complete AFF. RESULTS: Complete fractures occurred in 10 (9.7%) of 103 femurs without incomplete AFF at the first visit and in 3 (37.5%) of 8 femurs with incomplete AFF. The Kaplan-Meier curve revealed that lateral cortical bone thickening and thigh pain were associated with significantly poorer prognoses (p = 0.026 and p = 0.013, respectively). Multivariate analyses revealed that eldecalcitol usage after AFF onset (p = 0.0094) and previous use of bisphosphonate or denosumab (p = 0.0126) were protective factors for second complete AFF and that the presence of thigh pain (p = 0.0134) was a risk factor for second complete AFF. CONCLUSIONS: Eldecalcitol administration after bone union of first AFF may prevent AFF recurrence. In addition, painful incomplete AFF has a high risk of developing a complete fracture.

Reduced glutathione level in the aqueous humor of patients with primary open-angle glaucoma and normal-tension glaucoma.

Glaucoma is a leading cause of blindness worldwide in older people. Profiling the aqueous humor, including the metabolites it contains, is useful to understand physiological and pathological conditions in the eye. In the current study, we used mass spectrometry (MS) to characterize the aqueous humor metabolomic profile and biological features of patients with glaucoma. Aqueous humor samples were collected during trabeculectomy surgery or cataract surgery and analyzed with global metabolomics. We included 40 patients with glaucoma (32 with POAG, 8 with NTG) and 37 control subjects in a discovery study. VIP analysis revealed five metabolites that were elevated and three metabolites that were reduced in the glaucoma patients. The identified metabolomic profile had an area under the receiver operating characteristic curve of 0.953. Among eight selected metabolites, the glutathione level was significantly decreased in association with visual field defects. Moreover, in a validation study to confirm the reproducibility of our findings, the glutathione level was reduced in NTG and POAG patients compared with a cataract control group. Our findings demonstrate that aqueous humor profiling can help to diagnose glaucoma and that various aqueous humor metabolites are correlated with clinical parameters in glaucoma patients. In addition, glutathione is clearly reduced in the aqueous humor of glaucoma patients with both IOP-dependent and IOP-independent disease subtypes. These findings indicate that antioxidant agents in the aqueous humor reflect glaucomatous optic nerve damage and that excessive oxidative stress may be involved in the pathogenesis of glaucoma.

The GPR84 molecule is a mediator of a subpopulation of retinal microglia that promote TNF/IL-1α expression via the rho-ROCK pathway after optic nerve injury.

Resident microglia are important to maintain homeostasis in the central nervous system, which includes the retina. The retinal microglia become activated in numerous pathological conditions, but the molecular signatures of these changes are poorly understood. Here, using an approach based on FACS and RNA-seq, we show that microglial gene expression patterns gradually change during RGC degeneration induced by optic nerve injury. Most importantly, we found that the microglial cells strongly expressed Tnf and Il1α, both of which are known to induce neurotoxic reactive astrocytes, and were characterized by Gpr84high -expressing cells in a particular subpopulation. Moreover, ripasudil, a Rho kinase inhibitor, significantly blunted Gpr84 expression and cytokine induction in vitro and in vivo. Finally, GPR84-deficient mice prevented RGC loss in optic nerve-injured retina. These results reveal that Rho kinase-mediated GPR84 alteration strongly contribute to microglial activation and promote neurotoxicity, suggesting that Rho-ROCK and GPR84 signaling may be potential therapeutic targets to prevent the neurotoxic microglial phenotype induced by optic nerve damage, such as occurs in traumatic optic neuropathy and glaucoma.

Long-Term Surgical Outcomes and Possible Postoperative Complication with Severe Corneal Endothelial Cell Loss After Trabeculectomy for Cytomegalovirus-Associated Anterior Uveitis with Secondary Glaucoma.

PURPOSE: We assess long-term surgical outcomes after an initial trabeculectomy for cytomegalovirus-associated anterior uveitis with secondary glaucoma (CMV-SG). METHODS: We retrospectively reviewed the medical records of 16 eyes of 15 patients with CMV-SG and 157 eyes of 157 patients with primary open-angle glaucoma. The average follow-up period was approximately 3 years. Surgical success was defined as intraocular pressure (IOP) below 18 mmHg and at least 20% lower than baseline. RESULTS: Kaplan-Meier survival analysis revealed that bleb survival rates were not significantly different in the CMV-SG and POAG groups (P = 0.75). Bullous keratopathy occurred in 2 of 16 eyes with CMV-SG postoperatively but did not occur in the POAG group. The corneal endothelial cell density decreased by 34.2 ± 22.7% in the CMV-SG group during an average follow-up period of 2.7 ± 2.0 years. CONCLUSION: Trabeculectomy effectively controlled IOP in CMV-SG, but attention must be paid to corneal endothelial cell loss.

A Plant-Derived Antioxidant Supplement Prevents the Loss of Retinal Ganglion Cells in the Retinas of NMDA-Injured Mice.

Purpose: To investigate the effect of plant-derived antioxidant compounds, identified with primary culture screening, on retinal ganglion cell (RGC) survival in mice under excitotoxic conditions. Additionally, to determine the effect of these compounds on the involvement of calpain inactivation. Materials and Methods: Plant-derived antioxidant compounds including hesperidin, crocetin, and Tamarindus indica were administrated orally to C57BL/6J mice. The levels of lipid oxidation and calpain activation were assessed with a TBARS assay and western blotting. RGC survival was evaluated with a TUNEL assay and RBPMS immunostaining after intravitreal injection of NMDA. Results: Plant-derived antioxidant compounds significantly ameliorated the increase in the level of MDA in the retinas after NMDA injury. Cleaved α-fodrin fragments were detected in the NMDA-injured retinas, and these fragments were significantly lower in mice that received the plant-derived antioxidant compounds. The plant-derived antioxidants also ameliorated increases in TUNEL-positive cells and RGC death after NMDA injection. Conclusion: These results indicate that oral administration of plant-derived antioxidant compounds such as hesperidin, crocetin, and Tamarindus indica suppressed RGC death. This oral supplementation decreased lipid oxidation and excessive calpain activation in NMDA-injured retinas. Thus, our newly developed antioxidant supplement has a potential role in neuroprotective treatment for retinal diseases, such as glaucoma.

CHOP deletion and anti-neuroinflammation treatment with hesperidin synergistically attenuate NMDA retinal injury in mice.

Glaucoma is a leading cause of blindness worldwide and is characterized by degeneration associated with the death of retinal ganglion cells (RGCs). It is believed that glaucoma is a group of heterogeneous diseases with multifactorial pathomechanisms. Here, we investigate whether anti-inflammation treatment with an ER stress blockade can selectively promote neuroprotection against NMDA injury in the RGCs. Retinal excitotoxicity was induced with an intravitreal NMDA injection. Microglial activation and neuroinflammation were evaluated with Iba1 immunostaining and cytokine gene expression. A stable HT22 cell line transfected with an NF-kB reporter was used to assess NF-kB activity after hesperidin treatment. CHOP-deficient mice were used as a model of ER stress blockade. Retinal cell death was evaluated with a TUNEL assay. As results, in the NMDA injury group, Iba1-positive microglia increased 6 h after NMDA injection. Also at 6 h, pro-inflammatory cytokines and chemokine increased, including TNFα, IL-1b, IL-6 and MCP-1. In addition, the MCP-1 promoter-driven EGFP signal, which we previously identified as a stress signal in injured RGCs, also increased; hesperidin treatment suppressed this inflammatory response and reduced stressed RGCs. In CHOP-deficient mice that received an NMDA injection, the gene expression of pro-inflammatory cytokines, chemokines, markers of active microglia, and inflammatory regulators was greater than in WT mice. In WT mice, hesperidin treatment partially prevented retinal cell death after NMDA injury; this neuroprotective effect was enhanced in CHOP-deficient mice. These findings demonstrate that ER stress blockade is not enough by itself to prevent RGC loss due to neuroinflammation in the retina, but it has a synergistic neuroprotective effect after NMDA injury when combined with an anti-inflammatory treatment based on hesperidin.

Evaluation of the Nature and Etiologies of Risk Factors for Diaphyseal Atypical Femoral Fractures.

OBJECTIVES: Differences in mechanisms of subtrochanteric and diaphyseal atypical femoral fractures (AFFs) are speculated in studies that analyzed differences in the patients' background. However, the etiologies of each type of AFF have not been studied in detail. This study aimed to investigate the nature and etiologies of the risk factors for diaphyseal AFFs. MATERIALS AND METHODS: Eighty consecutive Japanese patients with 91 diaphyseal AFFs (AFF group) and 110 age-matched women with osteoporosis (non-AFF control group) were included. Their clinical data were compared; factors affecting AFFs were investigated, and the etiologies of the risk factors for diaphyseal AFFs were examined. RESULTS: Multivariate analysis revealed that femoral serrated changes, bisphosphonate or denosumab usage, and lateral and anterior femoral curvatures were risk factors for diaphyseal AFFs (p < 0.0011, p = 0.0137, and p < 0.0001, respectively). Multivariate analyses revealed that serrated changes and low serum 25(OH)D levels affected the lateral curvature (p = 0.0088 and 0.0205, respectively), while serrated changes affected the anterior curvature (p = 0.0006), each significantly affected the femoral curvature. High serum calcium (Ca) levels, lateral femoral curvature, and anterior femoral curvature were predictors of serrated changes (p = 0.0146, 0.0002, and 0.0098, respectively). CONCLUSION: Risk factors for diaphyseal AFFs were bone resorption inhibitor usage, a strong femoral curvature, and serrated changes. Low serum 25(OH)D levels and serrated changes are risk factors for lateral curvature, while a high serum Ca level is a risk factor for serrated changes.

Evaluation of factors affecting the occurrence of second atypical fracture after bone union of the first atypical fracture.

PURPOSE: Teriparatide is sometimes used in the treatment of atypical femoral fracture (AFF). Even if bone union is achieved, orthopedic physicians must consider the risk of relapse. This study aimed to investigate the factors affecting AFF recurrence, and to determine the appropriate treatment for osteoporosis after bone union. METHODS: One hundred thirty-one consecutive AFFs in 113 Japanese patients were included. Eleven patients had AFF in the unaffected limb (9 patients) after the first AFF or re-fracture at the original fracture site (2 patients) after bone union of the first AFF was confirmed. We divided all patients into two groups: the second fracture group (22 AFFs in 11 patients) and non-second fracture group (109 AFFs in 102 patients). We compared clinical information between the 2 groups and investigated the factors affecting AFF recurrence using the Student t-, Welch t-, and chi-square tests. RESULTS: Although there was no significant difference in clinical characteristics between the 2 groups, multivariate analysis of factors associated with AFF recurrence identified short duration of treatment with teriparatide and active vitamin D3 (p = 0.0408 and 0.0366, respectively) as risk factors. Even in the analysis excluding subtrochanteric AFF, short periods of teriparatide and active vitamin D3 administration were observed as risk factors (p = 0.0484 and 0.0346, respectively). CONCLUSION: The administration of teriparatide for as long as possible after occurrence first AFF and the use of active vitamin D3 after completion of teriparatide therapy may be the most effective strategy to prevent the recurrence of AFF.

Effects of Brimonidine and Timolol on the Progression of Visual Field Defects in Open-angle Glaucoma: A Single-center Randomized Trial.

PRéCIS:: Instillation of brimonidine or timolol slowed visual field deterioration in patients with open-angle glaucoma; both brimonidine and timolol might improve the mean deviation (MD) slopes. PURPOSE: The purpose of this study was to investigate and compare the effects of 0.1% brimonidine and 0.5% timolol on the progressing visual field defects in open-angle glaucoma. PATIENTS AND METHODS: We evaluated 1 eye each of 68 glaucoma patients who were treated with at least 1 prostaglandin analog. Their baseline MD slopes were < -0.5 dB/y based on at least 5 Humphrey field analyzer measurements within 3 years. Eligible eyes were randomly assigned to brimonidine or timolol treatment groups and treatments were administered without the wash-out period. Clinical examinations were performed every 4 months for 2 years. We designated the MD slope as the primary endpoint. RESULTS: Ultimately, 56 eyes (brimonidine:timolol=26:30) were included in the present study (mean age=65.2 y). Dropout rates of brimonidine and timolol treatment groups were 27.8% and 6.3%, respectively. There were no significant differences in baseline intraocular pressure or MD slopes between brimonidine and timolol groups (12.7 and 12.9 mm Hg, P=0.77, and -1.22 and -1.08 dB/y, P=0.43, respectively). Intraocular pressure decreased significantly in the brimonidine group at 4, 8, 12, and 16 months, and in the timolol group at 4 months, without significant differences between the drugs (P=0.20). MD slopes significantly improved in both groups (brimonidine: -0.38 dB/y, P<0.001; timolol: -0.52 dB/y, P=0.04). Furthermore, there was no significant difference between groups in the primary endpoint (P=0.59). CONCLUSION: Brimonidine and timolol treatments improved MD slopes in open-angle glaucoma.

Pilot study for three-dimensional assessment of laminar pore structure in patients with glaucoma, as measured with swept source optical coherence tomography.

PURPOSE: To develop a method to quantify, based on swept-source optical coherence tomography (OCT), the 3D structure of the laminar pores in patients with glaucoma. METHODS: This retrospective study examined 160 laminar pores from 8 eyes of 8 cases: 4 normal subjects and 4 open-angle glaucoma (OAG) patients. We reconstructed 3D volume data for a 3 x 3 mm disc, using a method similar to OCT angiography, and segmented the structure of the lamina cribrosa. Then, we manually segmented each laminar pore in sequential C-scan images (>90 slices at 2.6-micron intervals) with VCAT5 (RIKEN, Japan). We compared the control and OAG subjects with the Mann-Whitney U test. Differences were considered significant at p < 0.05. RESULTS: We found that the laminar pores of the OAG patients had a significantly smaller average cross-sectional area, smaller 3D volume (adjusted to the average thickness of the lamina cribrosa), and higher true sphericity, and lower principal value (P1, 2, 3) of the 3D structure data (all: p < 0.0001). The topographic distribution of damaged laminar pores was consistent with the damaged area of the macular map. CONCLUSION: We successfully developed a method to quantify the 3D structure of the laminar pores; providing a useful tool to assess lamina cribrosa-associated risk factors for glaucoma. These findings promise to benefit future investigations into the pathomechanisms of glaucoma.

Ecel1 Knockdown With an AAV2-Mediated CRISPR/Cas9 System Promotes Optic Nerve Damage-Induced RGC Death in the Mouse Retina.

Purpose: To assess the therapeutic potential of endothelin-converting enzyme-like 1 (Ecel1) in a mouse model of optic nerve crush. Methods: Ecel1 expression was evaluated with real time quantitative (qRT)-PCR, Western blotting, and immunohistochemistry in mouse retinas after optic nerve crush. Vinblastine administration to the optic nerve and the intravitreal injection of N-methyl-d-aspartate (NMDA) were used to assess Ecel1 gene expression. Ecel1 was deleted with an adeno-associated viral (AAV) clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas9 system, and retinal ganglion cell (RGC) survival was investigated with retrograde labeling, qRT-PCR, and visual evoked potential. Results: Optic nerve crush induced Ecel1 expression specifically in the RGCs, peaking on day 4 after optic nerve crush. Ecel1 gene expression was induced by the vinblastine-induced inhibition of axonal flow, but not by NMDA-induced excitotoxicity, even though both are triggers of RGC death. Knockdown of Ecel1 promoted the loss of RGCs after optic nerve crush. Conclusions: Our data suggest that Ecel1 induction is part of the retinal neuroprotective response to axonal injury in mice. These findings might provide insight into novel therapeutic targets for the attenuation of RGC damage, such as occurs in traumatic optic neuropathy.

Utilizing a Cortical Bone Trajectory Pedicle Screw for Lumbar Flexion-Distraction Injury.

Spinal flexion-distraction injuries (FDIs) are unstable fractures, commonly located at the thoracolumbar junction. Management of FDIs often necessitates the use of posterior instrumentation and fusion, but long-segment instrumentation surgery decreases postoperative spinal mobility and increases the risk of junctional kyphosis and fracture. We report the case of a patient with FDI showing an L2 vertebral fracture, unilateral L2 pedicle fracture, and disruptions of the posterior ligamentous complex between L1 and L2. After open reduction using L1 and L2 pedicle screws with a conventional trajectory on the right side, a cortical bone trajectory (CBT) pedicle screw was used as an osteosynthesis screw for the fractured left pedicle. This procedure enabled successful single-level fusion. Follow-up radiological examination revealed good reduction and complete bone union. To the best of our knowledge, utilizing a CBT technique as an osteosynthesis screw in FDIs has not previously been described.

Bilberry extract administration prevents retinal ganglion cell death in mice via the regulation of chaperone molecules under conditions of endoplasmic reticulum stress.

PURPOSE: To investigate the effect of bilberry extract anthocyanins on retinal ganglion cell (RGC) survival after optic nerve crush. Additionally, to determine details of the mechanism of the neuroprotective effect of bilberry extract anthocyanins and the involvement of endoplasmic reticulum stress suppression in the mouse retina. MATERIALS AND METHODS: Anthocyanins in bilberry extract (100 mg/kg/day or 500 mg/kg/day) were administrated orally to C57BL/6J mice. The expression levels of various molecular chaperones were assessed with quantitative reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry. RGC survival was evaluated by measuring the gene expression of RGC markers and counting retrogradely labeled RGCs after optic nerve crush. RESULTS: The protein levels of Grp78 and Grp94 increased significantly in mice after bilberry extract administration. Increased Grp78 and Grp94 levels were detected in the inner nuclear layer and ganglion cell layer of the retina, surrounding the RGCs. Gene expression of Chop, Bax, and Atf4 increased in mice after optic nerve crush and decreased significantly after oral bilberry extract administration. RGC survival after nerve crush also increased with bilberry extract administration. CONCLUSION: These results indicate that oral bilberry extract administration suppresses RGC death. Bilberry extract administration increased Grp78 and Grp94 protein levels, an effect which may underlie the neuroprotective effect of bilberry extract after optic nerve crush. Thus, bilberry extract has a potential role in neuroprotective treatments for retinal injuries, such as those which occur in glaucoma.

The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation.

We found that hesperidin, a plant-derived bioflavonoid, may be a candidate agent for neuroprotective treatment in the retina, after screening 41 materials for anti-oxidative properties in a primary retinal cell culture under oxidative stress. We found that the intravitreal injection of hesperidin in mice prevented reductions in markers of the retinal ganglion cells (RGCs) and RGC death after N-methyl-D-aspartate (NMDA)-induced excitotoxicity. Hesperidin treatment also reduced calpain activation, reactive oxygen species generation and TNF-α gene expression. Finally, hesperidin treatment improved electrophysiological function, measured with visual evoked potential, and visual function, measured with optomotry. Thus, we found that hesperidin suppressed a number of cytotoxic factors associated with NMDA-induced cell death signaling, such as oxidative stress, over-activation of calpain, and inflammation, thereby protecting the RGCs in mice. Therefore, hesperidin may have potential as a therapeutic supplement for protecting the retina against the damage associated with excitotoxic injury, such as occurs in glaucoma and diabetic retinopathy.

The Effect of Systemic Hyperoxia on Optic Nerve Head Blood Flow in Primary Open-Angle Glaucoma Patients.

Purpose: To assess the optic nerve head blood flow (ONH BF) response to hyperoxia in glaucoma patients using laser speckle flowgraphy (LSFG), and determine factors influencing vasoreactivity within the ONH. Methods: We performed oxygen provocation testing in 15 eyes of 15 primary open-angle glaucoma (POAG) patients and 15 eyes of 15 age-matched control subjects. During the test, LSFG-derived tissue mean blur rate (MBRT) and clinical variables, including blood pressure, were recorded. We evaluated differences in MBRT alteration during systemic hyperoxia between the groups. Additionally, we calculated the mean % change in MBRT against baseline and determined contributing factors. Results: Despite similar clinical variables during systemic hyperoxia in both groups, the mean % change in MBRT against baseline was significantly lower in the POAG than control subjects (P < 0.0001). Multiple regression analysis revealed that baseline MBRT and systolic blood pressure (SBP) were contributing factors to mean % change in MBRT (ß = 0.44, ß = -0.32, respectively). Additionally, baseline MBRT and SBP were strongly correlated to mean % change in MBRT only in the POAG group (r = 0.83, P < 0.0001; r = -0.60, P = 0.02, respectively). Conclusions: POAG patients had a weaker vasoreactive response to hyperoxia than controls, and this impaired response was associated with lower basal ONH BF and higher SBP. These findings suggest that pre-existing vasoconstriction in the ONH of eyes with glaucoma might reduce the capacity of the vasoconstrictive response to hyperoxia. Alternatively, the pathways that mediate hyperoxia-induced vasoconstriction could be altered in POAG.

Clinical Factors Associated with Lamina Cribrosa Thickness in Patients with Glaucoma, as Measured with Swept Source Optical Coherence Tomography.

PURPOSE: To investigate the influence of various risk factors on thinning of the lamina cribrosa (LC), as measured with swept-source optical coherence tomography (SS-OCT; Topcon). METHODS: This retrospective study comprised 150 eyes of 150 patients: 22 normal subjects, 28 preperimetric glaucoma (PPG) patients, and 100 open-angle glaucoma patients. Average LC thickness was determined in a 3 x 3 mm cube scan of the optic disc, over which a 4 x 4 grid of 16 points was superimposed (interpoint distance: 175 µm), centered on the circular Bruch's membrane opening. The borders of the LC were defined as the visible limits of the LC pores. The correlation of LC thickness with Humphrey field analyzer-measured mean deviation (MD; SITA standard 24-2), circumpapillary retinal nerve fiber layer thickness (cpRNFLT), the vertical cup-to-disc (C/D) ratio, and tissue mean blur rate (MBR) was determined with Spearman's rank correlation coefficient. The relationship of LC thickness with age, axial length, intraocular pressure (IOP), MD, the vertical C/D ratio, central corneal thickness (CCT), and tissue MBR was determined with multiple regression analysis. Average LC thickness and the correlation between LC thickness and MD were compared in patients with the glaucomatous enlargement (GE) optic disc type and those with non-GE disc types, as classified with Nicolela's method. RESULTS: We found that average LC thickness in the 16 grid points was significantly associated with overall LC thickness (r = 0.77, P < 0.001). The measurement time for this area was 12.4 ± 2.4 minutes. Average LC thickness in this area had a correlation coefficient of 0.57 with cpRNFLT (P < 0.001) and 0.46 (P < 0.001) with MD. Average LC thickness differed significantly between the groups (normal: 268 ± 23 µm, PPG: 248 ± 13 µm, OAG: 233 ± 20 µm). Multiple regression analysis showed that MD (ß = 0.29, P = 0.013), vertical C/D ratio (ß = -0.25, P = 0.020) and tissue MBR (ß = 0.20, P = 0.034) were independent variables significantly affecting LC thickness, but age, axial length, IOP, and CCT were not. LC thickness was significantly lower in the GE patients (233.9 ± 17.3 µm) than the non-GE patients (243.6 ± 19.5 µm, P = 0.040). The correlation coefficient between MD and LC thickness was 0.58 (P < 0.001) in the GE patients and 0.39 (P = 0.013) in the non-GE patients. CONCLUSION: Cupping formation and tissue blood flow were independently correlated to LC thinning. Glaucoma patients with the GE disc type, who predominantly have large cupping, had lower LC thickness even with similar glaucoma severity.