NMI,POLR3G and APIP are the key molecules connecting glaucoma with high intraocular pressure:a clue for early diagnostic biomarker candidates

AIM:To understand the molecular connectivity between the intraocular pressure(IOP)and glaucoma which will provide possible clues for biomarker candidates.METHODS:The current study uncovers the important genes connecting IOP with the core functional modules of glaucoma.An integrated analysis was performed using glaucoma and IOP microarray datasets to screen for differentially expressed genes(DEGs)in both conditions.To the selected DEGs,the protein interaction network was constructed and dissected to determine the core functional clusters of glaucoma.For the clusters,the connectivity of IOP DEGs was determined.Further,enrichment analyses were performed to assess the functional annotation and potential pathways of the crucial clusters.RESULTS:The gene expression analysis of glaucoma and IOP with normal control showed that 408 DEGs(277 glaucoma and 131 IOP genes)were discovered from two GEO datasets.The 290 DEGs of glaucoma were extended to form a network containing 1495 proteins with 9462 edges.Using ClusterONE,the network was dissected to have 12 clusters.Among them,three clusters were linked with three IOP DEGs[N-Myc and STAT Interactor(NMI),POLR3G(RNA Polymerase Ⅲ Subunit G),and APAF1-interacting protein(APIP)].In the clusters,ontology analysis revealed that RNA processing and transport,p53 class mediators resulting in cell cycle arrest,cellular response to cytokine stimulus,regulation of phosphorylation,regulation of type Ⅰ interferon production,DNA deamination,and cellular response to hypoxia were significantly enriched to be implicated in the development of glaucoma.Finally,NMI,POLR3G,and APIP may have roles that were noticed altered in glaucoma and IOP conditions.CONCLUSION:Our findings could help to discover new potential biomarkers,elucidate the underlying pathophysiology,and identify new therapeutic targets for glaucoma.

Intraocular pressure fluctuation and the risk of glaucomatous damage deterioration: a Meta-analysis

AIM: To systematically review whether the increased fluctuation of intraocular pressure(IOP) is a risk factor for open angle glaucoma(OAG) progression. METHODS: Scientific studies relevant to IOP fluctuation and glaucoma progression were retrieved from MEDLINE,EMBASE and CENTRAL databases, and were listed as references in this paper. The hazard ratio(HR) was calculated by using fixed or random-effects models according to the heterogeneity of included studies. RESULTS: Individual data for 2211 eyes of 2637 OAG patients in fourteen prospective studies were included in this Meta-analysis. All studies were longitudinal clinical studies with follow-up period ranging from 3 to 8.5 y. The combined HR was 1.23(95%CI 1.04-1.46, P=0.02) for the association between IOP fluctuation and glaucoma onset or progression with the evidence of heterogeneity(P<0.1).Subgroup analyses with different types of IOP fluctuation were also evaluated. Results indicated that the summary HR was 0.98(95%CI 0.78-1.24) in short-term IOP fluctuation group, which showed no statistical significance with heterogeneity, whereas, the combined HR was 1.43(95%CI1.13-1.82, P=0.003) in long-term IOP fluctuation group without homogeneity. Sensitivity analysis further showed that the pooled HR was 1.10(95%CI 1.03-1.18, P=0.004) for long-term IOP fluctuation and visual function progression with homogeneity among studies(P=0.3). CONCLUSION: Long-term IOP fluctuation can be a risk factor for glaucoma progression based on the presentedevidence. Thus, controlling the swing of IOP is crucial for glaucoma or glaucoma suspecting patients.

Intraocular pressure-lowering effects of commonly used fixed combination drugs with timolol in the management of primary open angle glaucoma

AIM:To evaluate intraocular pressure(IOP)-lowering effect and ocular tolerability of brimonidine/timolol,dorzolamide/timolol and latanoprost/timolol fixed combination therapies in the management of primary open angle glaucoma.· METHODS:Each drug was administered for two months, after which a circadian tonometric curve was recorded using a Goldmann applanation tonometer.Ocular discomfort(conjunctival hyperemia, burning or stinging, foreign body sensation, itching, ocular pain) of each eye was assessed by the subject on a standardized ocular discomfort scale.RESULTS:Among the three study groups, there were no significant differences in the mean baseline IOP measurements, mean 2ndmo IOP measurements, and mean(%) change of IOPs from baseline. Among the three study groups, there were no significant differences in the mean IOP measurements obtained at circadian tonometric curves at baseline and at two months controls. In sum brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar effects on IOP levels.· CONCLUSION:Brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar lowering efficaties on IOP levels whereas there was no any difference between each other.

Casein kinase-2 inhibition promotes retinal ganglion cell survival after acute intraocular pressure elevation

Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma,the leading cause of irreversible blindness.We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury.To investigate the underlying mechanism,in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor(4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole)by intravitreal injection.We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages.Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors.Furthermore,casein kinase-2 inhibition downregulated the expression of genes(Cck,Htrsa,Nef1,Htrlb,Prph,Chat,Slc18a3,Slc5a7,Scn1b,Crybb2,Tsga10ip,and Vstm21)involved in intraocular pressure elevation.Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.

Comparing posture induced intraocular pressure variations in normal subjects and glaucoma patients

AIM:To compare the posture-induced variations in intraocular pressure(IOP)between the primary open angle glaucoma(POAG)and non-glaucomatous eyes.METHODS:A case-controlled age matched study was conducted in 55 successive newly diagnosed POAG and 56 non-glaucomatous patients seen in glaucoma clinic and general outpatient eye clinic in the Alex Ekwueme University Teaching Hospital,Abakaliki.The IOPs of eligible correspondents were measured with Perkin’s hand-held tonometer in the sitting,supine flat and supine with pillow positions respectively.Measurement of IOP in each position was done after 15 min of assuming such posture.RESULTS:The IOP difference between the sitting and supine flat position was significantly higher in the POAG than non-glaucoma subjects(7.68±2.08 vs 4.03±0.13 mm Hg,P<0.001).The IOP difference between the sitting and supine with pillow positions was 2.61±1.49 mm Hg for POAG and 1.44±0.70 mm Hg in non-glaucoma(P<0.001),while difference between supine flat and supine with pillow positions was 5.07±2.24 mm Hg in POAG and 2.59±0.66 mm Hg in non-glaucomatous patients(P<0.001).CONCLUSION:Greater variations in posture induced IOP occurred in POAG patients than non-glaucomatous.The posture induced IOP variation is lowest in the sitting position and highest in the supine flat position.Evaluation of posture induced IOP changes may be an important tool in the management of glaucoma.

Association of peripheral anterior synechia,intraocular pressure,and glaucomatous optic neuropathy in primary angle-closure diseases

AIM:To investigate the association of peripheral anterior synechiae(PAS)with intraocular pressure(IOP)and glaucomatous optic neuropathy(GON)in primary angle closure(PAC)and primary angle-closure glaucoma(PACG).METHODS:Totally 355 eyes(238 PAC and 117 PACG)of 181 patients were included in this retrospective analysis of baseline data from a randomized clinical trial.All patients had undergone a comprehensive ophthalmic examination.The extent of PAS in clock hours as determined on gonioscopy was documented.The independent effect of the extent of PAS on IOP and the prevalence of GON were determined using multivariable generalized estimating equation(GEE)models.RESULTS:The frequency of GON increased with the extent of PAS and a higher IOP.PAS were more extensive(8 vs 1 clock hour,P<0.001)and IOP higher(28.01 vs 18.00 mm Hg,P<0.001)in PACG compared to PAC.The prevalence of GON among the PAS quartiles were 10.2%(PAS<0.5 clock hours),16.9%(PAS≥0.5 and PAS<3 clock hours),29.6%(PAS≥3 and PAS<7 clock hours),and 74.4%(PAS≥7 clock hours),respectively.After adjusting for IOP,age,gender,spherical equivalent,average Shaffer score and number of medications,the odds ratio(OR)for GON was 4.4(95%CI:1.5-13.0;P=0.007)with PAS≥3 clock hours and 13.8(95%CI:4.3-43.6;P<0.001)with PAS≥7 clock hours as compared to eyes with PAS<0.5 clock hours.The frequency of GON increased linearly with the extent of PAS.Extent of PAS was also associated with higher IOP.Eyes with both PAS≥6 clock hours and IOP≥21 mm Hg had the highest risk of GON compared to eyes with both PAS<6 clock hours and IOP<21 mm Hg(OR=18.0,95%CI:7.5-43.4;P<0.001).CONCLUSION:The extent of PAS in PAC and PACG is an important predictor of higher IOP and is linearly associated with GON independent of IOP,suggesting other factors related to PAS formation may be involved in the development of GON in PACG.

Bioinformatics analysis of potential essential genes that response to the high intraocular pressure on astrocyte due to glaucoma

AIM: To study the gene expression response and predict the network in cell due to pressure effects on optic nerve injury of glaucoma.METHODS: We used glaucoma related microarray data in public database [Gene Expression Omnibus(GEO)] to explore the potential gene expression changes as well as correspondent biological process alterations due to increased pressure in astrocytes during glaucoma development.RESULTS: A total of six genes were identified to be related with pressure increasing. Through the annotation and network analysis, we found these genes might be involved in cell morphological remodeling, angiogenesis,mismatch repair.CONCLUSION: Increasing pressure in glaucoma on astrocytes might cause gene expression alterations,which might induce some cellular responses changes.

Head trauma can cause transient elevation of intraocular pressure in patients with open angle glaucoma

AIM: To describe a newly-recognized entity, illustrated by five cases of glaucoma in whom trauma to the head, but not the eye, resulted in marked, transient elevation of intraocular pressure (IOP). METHODS: Retrospective case series. Chart review. RESULTS: All five cases had a diagnosis of primary open-angle glaucoma prior to the experience of trauma to the head. All cases had an unusual elevation of IOP (around 70 percent) for days to weeks following the trauma, after which the IOP fell to pre-accident levels. No cause other than the trauma could be determined. CONCLUSION: The relationship between head trauma and elevation of IOP appears real.

Comparison of intraocular pressure peak and fluctuations among Filipino patients with non-glaucomatous eyes and glaucoma suspects using water drinking test and diurnal intraocular pressure

AIM:To compare the intraocular pressure(IOP)peaks and fluctuations using water drinking tests(WDTs)and mean diurnal IOP among Filipino patients with normal eyes and glaucoma suspectsMETHODS:This prospective study included normal and glaucoma suspect patients.Each patient underwent both WDT and mean diurnal examination on separate visits.For mean diurnal examination,IOP was recorded every 2 h for 8 h while in WDT,IOP was recorded prior to WDT,and postWDT at 5,15,30,45,and 60 min.IOP peak was recorded as the highest IOP for both methods,and IOP fluctuation was recorded as highest IOP minus lowest IOP.RESULTS:With the comparison of diagnostic tests,both normal eyes and glaucoma suspect groups,the peak IOP was caught at 15 min.Comparative analysis of both groups also showed that the peak IOP measurements were statistically higher for the WDT compared to mean diurnal IOP(P=0.039,P=0.048 under normal group and P=0.032 and P=0.031 under glaucoma suspect group).Similarly,the WDT had a statistically higher mean IOP fluctuation score than the mean diurnal IOP method in both groups(P=0.003,P=0.011 under normal group;P=0.002 and P=0.005 under glaucoma suspect group).CONCLUSION:This study shows that WDT is a comparable diagnostic exam in predicting IOP fluctuations than mean diurnal measurement.WDT is a promising diagnostic procedure for risk assessment in glaucoma.

Impact of intraocular pressure fluctuations on progression of normal tension glaucoma

AIM:To investigate short-and long-term intraocular pressure(IOP)fluctuations and fur ther ocular and demographic parameters as predictors for normal tension glaucoma(NTG)progression.METHODS:This retrospective,longitudinal cohort study included 137 eyes of 75 patients with NTG,defined by glaucomatous optic disc or visual field defect with normal IOP(<21 mm Hg),independently from therapy regimen.IOP fluctuation,mean,and maximum were inspected with a mean follow-up of 38 mo[standard deviation(SD)18 mo].Inclusion criteria were the performance of minimum two 48-hour profiles including perimetry,Heidelberg retina tomograph(HRT)imaging,and optic disc photographs.The impact of IOP parameters,myopia,sex,cup-to-disc-ratio,and visual field results on progression of NTG were analyzed using Cox regression models.A sub-group analysis with results from optical coherence tomography(OCT)was performed.RESULTS:IOP fluctuations,average,and maximum were not risk factors for progression in NTG patients,although maximum IOP at the initial IOP profile was higher in eyes with progression than in eyes without progression(P=0.054).The 46/137(33.5%)eyes progressed over the followup period.Overall progression(at least three progression confirmations)occurred in 28/137 eyes(20.4%).Most progressions were detected by perimetry(36/46).Longterm IOP mean over all pressure profiles was 12.8 mm Hg(SD 1.3 mm Hg);IOP fluctuation was 1.4 mm Hg(SD 0.8 mm Hg).The progression-free five-year rate was 58.2%(SD 6.5%).CONCLUSION:Short-and long-term IOP fluctuations do not result in progression of NTG.As functional changes are most likely to happen,NTG should be monitored with visual field testing more often than with other devices.

Optimal screening interval for intraocular pressure measurement for Asian glaucoma patients

AIM: To explore the optimal interval of intraocular pressure(IOP) measurement for screening glaucoma in healthy people.METHODS: From January to December 2005, we consecutively enrolled all participants(> 20 years old) attending the Center for Preventive Medicine at St. Luke's International Hospital in Tokyo, Japan, for the annual health check program. The program promoted the early detection of chronic diseases and their risk factors. We excluded people who had glaucoma or a high IOP(≥ 22 mm Hg) at baseline. The annual health check-ups collected all demographic information and medical history with an initial evaluation, including IOP measurement. IOP was measured in both eyes with a full autotonometer TX-F(Canon, Tokyo, Japan). Participants with an IOP ≥ 22 mmH g in either eye were considered to require additional evaluation for glaucoma. We divided the participants into two groups based on age: under 65 years old and over 65 years old. The United States Department of Health and Human Services Cen-ters for Medicare and Medicaid Services guideline was used as a reference. RESULTS: From January 2005 to July 2008, 12 385 participants underwent check-ups each year. The mean ± SD IOP in the higher eye at baseline was 13.4(2.6) in 2005, 13.2(2.7) in 2006, 13.3(2.6), and 12.8(2.6) in 2008. In addition, we analyzed the differences with an analysis of variance(ANOVA), and additional analysis was performed with Bonferroni's correction. The difference between the 4 years was significant(P < 0.01) with ANOVA. Bonferroni analysis revealed significant differences between 2005 and 2006(P < 0.01), 2005 and 2008(P < 0.01), 2006 and 2007(P < 0.01), 2006 and 2008(P < 0.01), and 2007 and 2008(P < 0.01). Only the difference between 2005 and 2007 was not significant(P = 0.1). Logistic regression suggested that only age(P < 0.01) and baseline IOP(P < 0.01) were associated with high IOP; the presence of diabetes, HgbA 1c level, gender, systolic blood pressure, diastolic blood pressure, low-density lipoprotein and family history were non-significant.CONCLUSION: Annual IOP check-ups may be recommended for participants aged ≥ 65 years with baseline IOPs of 17-21 mm Hg. A check-up every 3 years or more may be recommended for patients with IOPs < 17 mmH g.

SEQUENTIAL INTRAOCULAR PRESSURE MEASUREMENTS IN SUSPECTED OPEN-ANGLE GLAUCOMA

Objective To evaluate the variations of intraocular pressure （lOP） in suspected open-angle glaucoma （OAG） patients. Methods The variations of lOP were measured in 216 eyes of suspected OAG patients at 4-hour intervals for 48 h. Based on the results of the serial lOP measurements, optic disc changed and visual field defected, the patients were diagnosed as primary OAG （ POAG ）, normal tension glaucoma （NTG）, ocular hypertension （ OHT） , or physiologic cup （PC）. Results After the serial lOP measurements, 16. 7% of the suspected OAG patients were diagnosed as POAG, 32. 4% as NTG, 24. 5% as OHT, and 26. 4% as PC. The highest percentages of the POAG group had peak lOP at 8 AM （19. 4% ） and their trough lOP at 10 PM （27. 8% ） ; the NTG group had peak lOP at 12 AM （18. 6% ） and their trough lOP at 12 PM （22. 9% ） ; the OHT group had peak lOP at 4 AM （22. 6% ） and their trough lOP at 10 PM （26. 4% ） ; and the PC group had peak lOP at 4 AM （ 21. 1% ） and their trough lOP at 12 PM （ 21. 1% ）. The percentages of peak lOP outside clinic （ 8 AM - 4 PM） in the POAG, NTG, OHT and PC groups were 55. 6%, 50. 0%, 58. 4% and 45. 7%, respectively. The mean magnitude of variance was 5. 1 - 6. 7 mmHg in those suspected OAG patients. There was a strong positive correlation in lOP between both eyes at each time point of measurement and the variation curves of the right and left eyes had parallel profiles in those suspected OAG patients. Conclusion Serial measurement of lOP is still needed, in order not to miss the peak and the trough lOP readings in suspected OAG patients, which helps in better management of glaucoma.

Diode Laser Cyclophotocoagulation in the Management of Pain and Intraocular Pressure Control in Patients with Terminal Glaucoma--Six Years’Experience

Objective: This study aims to describe the experience with diode laser cyclophotocoagulation in the control of intraocular pressure and resolution of pain in patients with refractory glaucoma. Methods: Retrospective study. 64 eyes of 60 patients who underwent cyclophotocoagulation between January 2008 and March 2014. Evaluation of the pre- and post-operative intraocular pressure, the control of ocular pain, the number of anti-glaucoma drugs used in pre- and post-intervention, the rate of complications and the success rate. Results: There was an overall success rate of 81.3%, with 9 eyes needing a second intervention. There was a mean reduction of 52.6% of the preoperative mean intraocular pressure of 41.25 to 19.56 mmHg at 12 months observation (p < 0.001). There was also a statistically significant reduction in the number of anti-glaucoma drugs used from 3.19 to 2.01 per eye and the resolution of pain in 75% of patients. Conclusions: cyclophotocoagulation is an effective procedure, with an expected positive impact on quality of life of patients as a result from the decreased number of anti-glaucoma drugs, sustained intraocular pressure reduction and resolution of pain.

Immediate intraocular pressure rise after intravitreal injection of ranibizumab and two doses of triamcinolone acetonide

AIM: To evaluate prospectively immediate intraocular pressure (IOP) changes after the intravitreal injection of ranibizumab, 2 and 4mg triamcinolone acetonide. METHODS: Patients who underwent intravitreal injection of 0.1mL (4mg) triamcinolone acetonide (TA, Group T4), 0.05mL (2mg) TA (Group T2) and 0.05mL (0.5mg) ranibizumab (Group R) comprised the study population. Overall, 229 eyes of 205 patients were injected. Fifty-four eyes (23.6%) were in Group T4, 69 eyes (30.1%) in Group T2 and 106 eyes (46.3%) in Group R. If IOP was less than 26mmHg immediately after the injection no further measurement was performed. If IOP was ≥26mmHg, IOP was remeasured till the reading was below 26mmHg at 5, 15 and 30 minutes. RESULTS: Immediately after the injection, the IOP of 28 eyes (51.9%) in Group T4, 22 eyes (31.9%) in Group T2 and 51 eyes (48.1%) in Group R were over 25mmHg. At 30 minutes, IOP of one eye (1.9%) in group T4, two eyes (2.9%) in group T2 and two eyes (1.9 %) in Group R were over 25mmHg. Immediate post-injection IOP was significantly higher in Group T4 and Group R when compared to Group T2 (P <0.001 and P <0.001, respectively). IOP was significantly higher in eyes without vitreous reflux when compared to those with vitreous reflux in all groups (P <0.001). CONCLUSION: IOP may remarkably increase immediately after the intravitreal injection of 2 or 4mg triamcinolone acetonide, and 0.5mg ranibizumab. Absence of vitreous reflux is the most important predicting factor for immediate IOP rise after the injection.

Effect of persistent high intraocular pressure on microstructure and hydraulic permeability of trabecular meshwork

As the aqueous humor leaves the eye, it first passes through the trabecular meshwork （TM）. Increased flow resistance in this region causes elevation of intraocular pressure （IOP）, which leads to the occurrence of glaucoma. To quantitatively evaluate the effect of high IOP on the configuration and hydraulic permeability of the TM, second harmonic generation （SHG） microscopy was used to image the microstructures of the TM and adjacent tissues in control （normal） and high IOP conditions. Enucleated rabbit eyes were perfused at a pressure of 60 mmHg to achieve the high lOP. Through the anterior chamber of the eye, in situ images were obtained from different depths beneath the surface of the TM. Porosity and specific surface area of the TM in control and high IOP conditions were then calculated to estimate the effect of the high pressure on the permeability of tissue in different depths. We further photographed the histological sections of the TM and compared the in situ images. The following results were obtained in the control condition, where the region of depth was less than 55 μm with crossed branching beams and large pores in the superficial TM. The deeper meshwork is a silk-like tissue with abundant fluorescence separating the small size of pores. The total thickness of pathway tissues composed of TM and juxtacanalicular （JCT） is more than 100 p.m. After putting a high pressure on the inner wall of the eye, the TM region progressively collapses and decreases to be less than 40 μm. Fibers of the TM became dense, and the porosity at 34 μm in the high IOP condition is comparable to that at 105 μm in the control condition. As a consequent result, the permeability of the superficial TM decreases rapidly from 120 μm2 to 49.6 μm2 and that of deeper TM decreases from 1.66 μm2 to 0.57 μm2. Heterogeneity reflected by descent in permeability reduces from 12.4 μm of the control condition to 3.74 μm of the high IOP condition. The persistently high IOP makes the TM region collapse from its normal state, in which the collagen fibers of the TM are arranged in regular to maintain the physiological permeability of the outflow pathway. In the scope of pathologically high IOP, the microstructure of the TM is sensitive to pressure and hydraulic permeability can be significantly affected by IOP.

Visual functional changes during acute elevation of intraocular pressure

Glaucoma is closely related to elevation of intraocular pressure （IOP）. Many studies have done on the effect of chronic elevation of lOP on the retina and optic nerve, but less attention was paid to the effect of acute elevated lOP. Here we briefly review experimental studies on functional changes of the visual system from the retina to the visual cortex under acute elevated lOP condition, which is similar to that of acute primary angle-closure glaucoma.

The effect of increased intra-abdominal pressure on orbital subarachnoid space width and intraocular pressure

In accordance with the trans-lamina cribrosa pressure difference theory, decreasing the trans-lamina cribrosa pressure difference can re- lieve glaucomatous optic neuropathy. Increased intracranial pressure can also reduce optic nerve damage in glaucoma patients, and a safe, effective and noninvasive way to achieve this is by increasing the intra-abdominal pressure. The purpose of this study was to observe the changes in orbital subarachnoid space width and intraocular pressure at elevated intra-abdominal pressure. An inflatable abdominal belt was tied to each of 15 healthy volunteers, aged 22-30 years （12 females and 3 males）, at the navel level, without applying pressure to the abdomen, before they laid in the magnetic resonance imaging machine. The baseline orbital subarachnoid space width around the optic nerve was measured by magnetic resonance imaging at 1, 3, 9, and 15 mm behind the globe. The abdominal belt was inflated to increase the pressure to 40 mmHg （1 mmHg = 0.133 kPa）, then the orbital subarachnoid space width was measured every 10 minutes for 2 hours. After removal of the pressure, the measurement was repeated 10 and 20 minutes later. In a separate trial, the intraocular pressure was measured for all the subjects at the same time points, before, during and after elevated intra-abdominal pressure. Results showed that the baseline mean orbital subarachnoid space width was 0.88 ＋ 0.1 mm （range： 0.77-1.05 mm）, 0.77 ＋ 0.11 mm （range： 0.60-0.94 mm）, 0.70 ＋ 0.08 mm （range： 0.62-0.80 ram）, and 0.68 _＋ 0.08 mm （range： 0.57-0.77 mm） at 1, 3, 9, and 15 mm behind the globe, respectively. During the elevated intra-abdominal pressure, the orbital subarachnoid space width increased from the baseline and dilation of the optic nerve sheath was significant at 1, 3 and 9 mm behind the globe. After decompression of the abdominal pressure, the orbital subarachnoid space width normalized and returned to the baseline value. There was no significant difference in the intraocular pressure before, during and after the intra-abdominal pressure elevation. These results verified that the increased intra-abdominal pressure widens the orbital subarachnoid space in this acute trial, but does not alter the intraocular pressure, indicating that intraocular pressure is not affected by rapid increased in- tra-abdominal pressure. This study was registered in the Chinese Clinical Trial Registry （registration number： ChiCTR-ONRC-14004947）.

Longitudinal observation of intraocular pressure variations with acute altitude changes

BACKGROUND Higher intraocular pressure(IOP)is a major risk factor for developing glaucoma,and the leading cause of irreversible blindness worldwide.High altitude(HA)may be involved in IOP,but the reported results were conflicting.Ascent to HA directly by plane from low altitude regions is an acute,effortless exposure.However,the effects of such exposure to different altitudes on IOP have rarely been reported.AIM To investigate changes in IOP after rapid effortless exposure to HA in stages and compare it with systemic parameters.METHODS Fifty-eight healthy subjects(116 eyes)were divided into three groups:17 lowaltitude(LA)residents[44 m above sea level(ASL)],22 HA residents(2261 m ASL)and 19 very HA(VHA)residents(3750 m ASL).The LA group flew to HA first.Three days later,they flew with the HA group to VHA where both groups stayed for 2 d.Then,the LA group flew back to HA and stayed for 1 d before flying back to 44 m.IOP,oxygen saturation(SpO2)and pulse rate were measured.The linear mixed model was used to compare repeated measurements.RESULTS IOP in the LA group significantly decreased from 18.41±2.40 mmHg at 44 m to 13.60±3.68 mmHg at 2261 m ASL(P<0.001),and then to 11.85±2.48 mmHg at 3750 m ASL(P=0.036 compared to IOP at 2261 m ASL)and partially recovered to 13.47±2.57 mmHg upon return to 44 m.IOP in the LA group at HA and VHA was comparable to that in the local residents(12.2±2.4 mmHg for HA,11.5±1.8 mmHg for VHA).IOP was positively associated with SpO2 while negatively associated with pulse rate.CONCLUSION IOP in the LA group gradually reduced as altitude elevated in stages and became comparable to IOP in local residents.Hypoxia may be associated with IOP,which deserves further study.

Time Course of Age-dependent Changes in Intraocular Pressure and Retinal Ganglion Cell Death in DBA/2J Mouse

Purpose:To characterizes the progression of glaucoma in DBA/2J mice by measuring intraocular pressure(IOP) and retinal ganglion cells(RGCs) numbers in mice of various ages. Methods:A quantitative assessment of the pathophysiology of the DBA/2J mice was performed and the C57/BL6 mice was used as control. The IOP was measured by the servo-null micropipette system; the regional patterns of the loss of RGCs were determined by cell count of retrogradely-labeled RGCs. Results:The baseline IOP for DBA/2J mice at 7 weeks was (16.6 ± 1.2)mm Hg.Then IOP increased extend to 12 months, with the peak of (25.2 ± 1.2)mm Hg at 6 months of age. Retinal ganglion cell numbers did not decrease relative to control until 12 months of age(P=0.006), when the loss was proportionally higher in peripheral regions(P<0.05). Conclusion:The elevation in IOP precedes the loss of RGCs by several months. RGCs cell loss occurs particularly in peripheral regions of the retina. These findings expand our understanding of the changes in DBA/2J mice and provide information for experiments design when they are used as a glaucoma model for future studies of RGCs degeneration in glaucoma.

Biomechanics of the sclera and effects on intraocular pressure

Accumulating evidence indicates that glaucoma is a multifactorial neurodegenerative disease characterized by the loss of retinal ganglion cells （RGC）, resulting in gradual and progressive permanent loss of vision. Reducing intraocular pressure （IOP） remains the only proven method for preventing and delaying the progression of glaucomatous visual impairment. However, the specific role of IOP in optic nerve injury remains controversial, and little is known about the biomechanical mechanism by which elevated IOP leads to the loss of RGC. Published studies suggest that the biomechanical properties of the sclera and scleral lamina cribrosa determine the biomechanical changes of optic nerve head, and play an important role in the pathologic process of loss of RGC and optic nerve damage. This review focuses on the current understanding of biomechanics of sclera in glaucoma and provides an overview of the possible interactions between the sclera and IOP. Treatments and interventions aimed at the sclera are also discussed.