Neuroimaging in atypical normal tension glaucoma:debating routine implementation in the absence of classic neurological findings

●AIM:To assess the necessity of neuroimaging in patients with neurological or atypical findings of normal tension glaucoma(NTG)who do not exhibit typical glaucoma manifestations.●METHODS:A retrospective analysis was conducted on 90 atypical NTG patients who underwent cranial magnetic resonance imaging(MRI)due to atypical symptoms.The demographic characteristics,clinical parameters,and radiological findings were recorded.●RESULTS:Among the patients,66.7%had abnormal radiology results,with the most common findings being gliosis(34.4%),sequelae of cerebrovascular events and vascular malformations(14.4%),and benign intracranial mass lesions(11%).Non-glaucomatous visual field defects were more frequently observed in patients with abnormal neuroimaging results.However,there were no significant differences in intraocular pressure,optic disc parameters,retinal nerve fiber layer thickness,and visual field indices between patients with normal and abnormal radiological results.The mean age of the patients was 58.74y.Interestingly,there was a significant age difference,with the abnormal radiology group having a higher median age(P=0.021).●CONCLUSION:The study highlights the importance of cranial imaging in older NTG patients to detect underlying pathologies and prevent misdiagnosis.It suggests that neuroimaging may be warranted in NTG patients with atypical visual field defects incompatible with glaucoma.However,routine neuroimaging in all NTG patients without classic neurological signs may not be necessary.

Regulatory mechanisms of retinal ganglion cell death in normal tension glaucoma and potential therapies

Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have described the mechanisms underlying the pathogenesis of NTG.In addition to controlling intraocular pressure,neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG.In this review,we summarized the main regulatory mechanisms of RGC death in NTG,including autophagy,glutamate neurotoxicity,oxidative stress,neuroinflammation,immunity,and vasoconstriction.Autophagy can be induced by retinal hypoxia and axonal damage.In this process,ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway.Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate,which occurs in RGCs and induces progressive glaucomatous optic neuropathy.Oxidative stress also participates in NTG-related glaucomatous optic neuropathy.It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway.Moreover,it increases inflammation and the immune response of RGCs.Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow,promoting vasospasm and glaucomatous optic neuropathy,as a result of NTG.In conclusion,we discussed research progress on potential options for the protection of RGCs,including TANK binding kinase 1 inhibitors regulating autophagy,N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity,ASK1 inhibitors regulating mitochondrial function,and antioxidants inhibiting oxidative stress.In NTG,RGC death is regulated by a network of mechanisms,while various potential targets protect RGCs.Collectively,these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.

Comparisons of ganglion cell-inner plexiform layer loss patterns and its diagnostic performance between normal tension glaucoma and primary open angle glaucoma: a detailed, severity-based study

AIM: To evaluate the patterns of macular ganglion cell-inner plexiform layer(GCIPL) loss in normal tension glaucoma(NTG) and primary open angle glaucoma(POAG) in a detailed, disease severity-matched way;and to assess the diagnostic capabilities of GCIPL thickness parameters in discriminating NTG or POAG from normal subjects.METHODS: A total of 157 eyes of 157 subjects, including 57 normal eyes, 51 eyes with POAG and 49 eyes with NTG were enrolled and strictly matched in age, refraction, and disease severity between POAG and NTG groups. The average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal GCIPL thickness, and the average, superior, temporal, inferior, and nasal retinal nerve fiber layer(RNFL) thickness were obtained by Cirrus optical coherence tomography(OCT). The diagnostic capabilities of OCT parameters were assessed by area under receiver operating characteristic(AUROC) curves. RESULTS: Among all the OCT thickness parameters, no statistical significant difference between NTG group and POAG group was found(all P>0.05). In discriminating NTG or POAG from normal subjects, the average and inferior RNFL thickness, and the minimum GCIPL thickness had better diagnostic capabilities. There was no significant difference in AUROC curve between the best GCIPL thickness parameter(minimum GCIPL) and the best RNFL thickness parameter in discriminating NTG(inferior RNFL;P=0.076) and indiscriminating POAG(average RNFL;P=0.913) from normal eyes.CONCLUSION: Localized GCIPL loss, especially in the inferior and inferotemporal sectors, is more common in NTG than in POAG. Among all the GCIPL thickness parameters, the minimum GCIPL thickness has the best diagnostic performance in differentiating NTG or POAG from normal subjects, which is comparable to that of the average and inferior RNFL thickness.

Intraocular retinal thickness asymmetry in early stage of primary open angle glaucoma and normal tension glaucoma

AIM： To investigate the intraocular retinal thickness asymmetry of peripapillary retinal nerve fiber layer（pR NFL） and macular layers measured by spectral-domain optical coherence tomography（SD-OCT） in patients with early stage of primary open angle glaucoma（POAG） and normal tension glaucoma（NTG）.METHODS： A total of 117 patients with early stage of glaucoma（54 patients with POAG and 63 patients with NTG） and 32 normal subjects were recruited for the study. The pR NFL thickness, total macular layer（TML） thickness, and isolated inner macular layer（IML） thickness were measured by SD-OCT. Hemisphere TML thickness asymmetry measured by the posterior pole asymmetry scan was evaluated. Thickness differences of pR NFL and IML between superior and inferior quadrants were calculated. Asymmetry indices（AIs） of the p RNFL, TML and isolated IML were also computed. Areas under the receiver-operating characteristic curves（AROCs） were generated to determine the diagnostic capabilities of different parameters. RESULTS： Intraocular p RNFL thickness differences and AIs between the superior and inferior quadrants were significantly different between normal and NTG groups（P=0.009 and P〈0.001, respectively）. Intraocular p RNFL thickness differences and AIs between the temporal-superior and temporal-inferior sectors were also significantly different between normal and NTG groups（P=0.035 and P〈0.001, respectively）. The thickness differences and AIs of TML between superior and inferior hemispheres were significantly different between normal and NTG groups（P=0.001 and P=0.001, respectively） and between normal and POAG groups（P=0.032 and P=0.020, respectively）. The thickness differences and AIs of macular ganglion cell layer（mG CL） between superior and inferior quadrants were significantly different between normal and NTG groups（P=0.013 and P=0.004, respectively）, and between NTG and POAG groups（P=0.015 and P=0.012, respectively）. The thickness difference of TML between superior and inferior hemispheres showed the highest diagnostic capability for early NTG eyes（AROC=0.832）.CONCLUSION： Intraocular retinal thickness asymmetry in pR NFL, TML and mG CL are found in early stage of NTG. Hemisphere TML thickness asymmetry is also found in POAG eyes. Asymmetry analysis of retinal thickness can be an adjunctive modality for early detection of glaucoma.

Comparison of corneal biomechanical properties in normal tension glaucoma patients with different visual field progression speed

AIM：To compare the corneal biomechanical properties difference by ocular response analyzer（ORA） in normal tension glaucoma（NTG） patients with different visual field（VF） progression speed. METHODS：NTG patients with well-controlled Goldmann applanation tonometer（GAT） who routinely consulted Kitasato University Hospital Glaucoma Department between January 2010 and February 2014 were enrolled.GAT and ORA parameters including corneal compensated intraocular pressure（lOPcc）,Goldmann estimated intraocular pressure（lOPg）,corneal hysteresis（CH）,corneal resistance factor（CRF） were recorded.VF was tested by Swedish interactive threshold algorithm（SITA）-standard 30-2 fields.All patients underwent VF measurement regularly and GAT did not exceed 15 mm Hg at any time during the 3y follow up.Patients were divided into four groups according to VF change over 3y,and ORA findings were compared between the upper 25th percentile group（slow progression group） and the lower 25th percentile group（rapid progression group）.RESULTS：Eighty-two eyes of 56 patients were studied.There were 21 eyes（21 patients） each in rapid and slow progression groups respectively.GAT,lOPcc,lOPg,CH,CRF were 12.1＋1.4 mm Hg,15.8±1.8 mm Hg,12.8±2.0 mm Hg,8.4±1.1 mm Hg,7.9±1.3 mm Hg respectively in rapid progression group and 11.5±1.3 mm Hg,13.5±2.1 mm Hg,11.2±1.6 mm Hg,9.3±1.1 mm Hg,8.2±0.9 mm Hg respectively in slow progression group（P=0.214,〈0.001,0.007,0.017,0.413,respectively）.In bivariate correlation analysis,lOPcc,lOPcc-GAT and CH were significant correlated with m△MD（r =-0.292,-0.312,0.228 respectively,P =0.008,0.004,0.039 respectively）.CONCLUSION：Relatively rapid VF progression occurred in NTG patients whose lOPcc are rather high,CH are rather low and the difference between lOPcc and GAT are relatively large.Higher lOPcc and lower CH are associated with VF progression in NTG patients.This study suggests that GAT measures might underestimate the IOP in such patients.

Association of n3 and n6 polyunsaturated fatty acids in red blood cell membrane and plasma with severity of normal tension glaucoma

AIM: To determine whether red blood cell(RBC)membrane and plasma lipids, particularly long-chain polyunsaturated fatty acids such as eicosapentaenoic acid(EPA), docosahexaenoic acid(DHA), arachidonic acid(AA) are significantly correlated with severity of normal tension glaucoma(NTG).METHODS: This study included 35 patients with NTG and 12 healthy normal control subjects, matched for age and sex with the study group. The stage of glaucoma was determined according to the Hodapp-Parrish-Anderson classification. Lipids were extracted from RBC membranes and plasma, and fatty acid methyl esters prepared and analyzed by gas chromatography-mass spectrometry(GC-MS).RESULTS: When RBC lipids were analyzed, the levels of EPA, the levels of DHA and the ratio of n3 to n6 were positively associated with the Humphrey Perimetry mean Deviation(MD) score(r =0.617, P 【0.001; r =0.727, P 【0.001 and r =0.720, P 【0.001, respectively), while the level of AA was negatively associated with the MD score(r =-0.427, P =0.001). When plasma lipids were analyzed,there was a significant positive relationship between the levels of EPA and the MD score(r =0.648, P 【0.001), and the levels of AA were inversely correlated with the MD score(r =-0.638, P 【0.001). CONCLUSION: The levels of n3 and n6 polyunsaturated fatty acids in RBC membrane and plasma lipids were associated with severity of NTG.

Normal tension glaucoma: from the brain to the eye or the inverse?

Glaucoma is a chronic, progressive optic neuropathy characterized by the loss of peripheral vision first and then central vision. Clinically, normal tension glaucoma is considered a special subtype of glaucoma, in which the patient’s intraocular pressure is within the normal range, but the patient experiences typical glaucomatous changes. However, increasing evidence has challenged the traditional pathophysiological view of normal tension glaucoma, which is based only on intraocular pressure, and breakthroughs in central nervous system imaging may now greatly increase our knowledge about the mechanisms underlying normal tension glaucoma. In this article, we review the latest progress in understanding the pathogenesis of normal tension glaucoma and in developing imaging techniques to detect it, to strengthen the appreciation for the connection between normal tension glaucoma and the brain.

The Comparison Study of Renin and Angiotensin AⅡ Levels on Normal Tension Glaucoma Patients and Normal Individuals

Purpose: To investigate the levels of renin-angiotension system (RAS) components in normal tension glaucoma patients and normal controls. Methods: Blood samples were obtained from 11 normal tension glaucoma(NTG)patients and 11 age and sex matched controls. The levels of renin and angiotensin AⅡof 11 NTG patients and normal controls were examined by radio-immunity test. Statistical analyses were performed by paired t test. Results:The levels of renin of NTG patients and normal controls are (769.085±183.217) pg/ml/n and (822.035 ±124.140) pg/ml/n, while the levels of angiotensin A Ⅱof NTG patients and normal controls are (37.347±10.669)pg/ml and (24.836±10.665)pg/ml respectively. No statistically significant differences were observed between the levels of renin and angiotensin among NTG patients and normal controls. Conclusion: There were not many abnormalities of the levels of circulating rennin and angiotensin AⅡof NTG patients in our study. Eye Science 2005 ;21 :192-195.

Unveiling the silent link:Normal-tension glaucoma's enigmatic bond with cardiac blood flow

This comprehensive review embarks on a captivating journey into the complex relationship between cardiology and normal-tension glaucoma(NTG),a condition that continues to baffle clinicians and researchers alike.NTG,characterized by optic nerve damage and visual field loss despite normal intraocular pressure,has long puzzled clinicians.One emerging perspective suggests that alterations in ocular blood flow,particularly within the optic nerve head,may play a pivotal role in its pathogenesis.While NTG shares commonalities with its high-tension counterpart,its unique pathogenesis and potential ties to cardiovascular health make it a fascinating subject of exploration.It navigates through the complex web of vascular dysregulation,blood pressure and perfusion pressure,neurovascular coupling,and oxidative stress,seeking to uncover the hidden threads that tie the heart and eyes together in NTG.This review explores into the intricate mechanisms connecting cardiovascular factors to NTG,shedding light on how cardiac dynamics can influence ocular health,particularly in cases where intraocular pressure remains within the normal range.NTG's enigmatic nature,often characterized by seemingly contradictory risk factors and clinical profiles,underscores the need for a holistic approach to patient care.Drawing parallels to cardiac health,we examine into the shared vascular terrain connecting the heart and the eyes.Cardiovascular factors,including systemic blood flow,endothelial dysfunction,and microcirculatory anomalies,may exert a profound influence on ocular perfusion,impacting the delicate balance within the optic nerve head.By elucidating the subtle clues and potential associations between cardiology and NTG,this review invites clinicians to consider a broader perspective in their evaluation and management of this elusive condition.As the understanding of these connections evolves,so too may the prospects for early diagnosis and tailored interventions,ultimately enhancing the quality of life for those living with NTG.

The change of anterior segment parameters after cataract surgery in normal-tension glaucoma

AIM： To investigate the change of anterior chamber angle morphology and intraocular pressure （lOP） reduction after cataract surgery in patients with normal-tension glaucoma （NTG） using swept-source optical coherence tomography （SS-OCT）. METHODS： This prospective, comparative, observational study recruited patients into two groups. Group 1 was the control group including normal subjects except those with cataracts （cataract group, n=67 eyes of 67 patients）, and group 2 was NTG group including patients who were diagnosed with NTG and cataracts （n=43 eyes of 43 patients）, which were treated with phacoemulsification and intraocular lens implantation. Before surgery, and at postoperative 1 and 6too, anterior chamber angles were evaluated by SS-OCT under dark conditions using three- dimensional angle analysis scan protocol. Angle opening distance （AOD）, angle recess area （ARA）, and trabecular- iris surface area （TISA） at four quadrants （temporal, nasal, superior, and inferior） were calculated automatically by SS-OGT, after the observer marked scleral spurs. RESULTS： A total of 106 patients （54 males and 52 females） were enrolled in the study. Angle parameters, AOD, ARA, and TISA were increased after surgery in both groups. However, changes of angle parameters were only significant in group 2. In group 2, preoperative lOP was 13.2＋2.9 mm Hg, and postoperative lOP at 1 and 6mo were 10.5＋3.0 and 10.7＋2.8 mm Hg, respectively. In group 1, preoperative lOP was 12.42.8 mm Hg, and postoperative lOP at 1 and 6mo were 11.6＋2.5 and 12.0＋2.8 mm Hg, respectively. After cataract surgery, angle parameters changed significantly while IOP significantly reduced and was maintained in group 2 （P〈0.001）. The changes in angle parameters （＆AOD500, ATISAS00 at temporal; ＆AOD500, S, RA500 at nasal） were linearly correlated with postoperative IOP changes. CONCLUSION： Cataract surgery may have improved antedor chamber angle parameters and decreased lOP in NTG patients.

剔络养血明目汤对正常眼压性青光眼患者眼部血流的影响

目的观察剔络养血明目汤对正常眼压性青光眼(NTG)患者眼部血流的影响。方法纳入2018年6月—2021年12月中国中医科学院眼科医院诊治的NTG患者32例(63只眼),辨证为瘀血阻络证。随机分为治疗组20例(39只眼)和对照组12例(24只眼)。对照组予银杏叶片和甲钴胺片口服;治疗组在对照组的基础上联合剔络养血明目汤口服。2组均观察28 d。分别于治疗前、后检测受试者的视神经总扫描区域的血流密度(VD1)及视盘周围毛细血管区域的血流密度(VD2),视网膜中央动脉(CRA)和睫状后短动脉(SPCA)的收缩峰值速度(PSV)、舒张末期速度(EDV)和阻力指数(RI)。结果2组治疗前VD1、VD2、EDV、PSV和RI比较,差异均无统计学意义(P>0.05);且对照组治疗后VD1、VD2、CRA和SPCA的PSV、EDV、RI与治疗前比较,差异均无统计学意义(P>0.05)。(1)VD:治疗组治疗后VD1、VD2均较治疗前升高,差异均有统计学意义(tVD1=6.739、tVD2=8.285,均P=0.000)。治疗后2组间VD1、VD2比较,差异无统计学意义(P>0.05)。治疗组治疗前、后的VD1差值与VD2差值均高于对照组,差异均有统计学意义(tVD1=5.599、tVD2=6.210,均P=0.000)。(2)眼部血管血流动力学参数:治疗组治疗后CRA的EDV较治疗前增加、RI较治疗前降低,差异均有统计学意义(tEDV=3.096,P=0.003;tRI=2.446,P=0.017);治疗后2组间CRA的各指标比较,差异均无统计学意义(P>0.05)。治疗组治疗后SPCA的PSV、EDV均较治疗前增加,差异均有统计学意义(tPSV=2.481,P=0.015;tEDV=2.315,P=0.023);治疗后2组间SPCA的各指标比较,差异均无统计学意义(P>0.05)。结论剔络养血明目汤可改善NTG患者的眼部血流,尤其是视神经血流。

正常眼压性青光眼患者黄斑区微循环状态与视功能改变的关系研究

目的 联合使用光学相干断层扫描血管成像(OCTA)和微视野计探讨正常眼压性青光眼(NTG)患者黄斑区微循环状态和视功能变化情况,并分析两者之间的相关性。方法 横断面观察性研究。收集NTG患者17例30眼作为NTG组,按病情严重程度分为轻度、中度和重度NTG组3组。选取同期年龄、性别相匹配的健康体检者13例23眼作为对照组。使用OCTA获取黄斑区浅层视网膜血管线性密度(LD)及灌注密度(PD)。使用微视野计检测黄斑区10°范围的视网膜光敏感度(RS)及2°、4°固视率。比较各组间OCTA参数及微视野计参数的差异,并分析NTG患者OCTA参数与微视野计参数之间的相关性。结果 对照组与轻度NTG组受试者之间除黄斑区中央和鼻侧的LD、PD差异均无统计学意义外,其余各区域和整体平均LD、PD在对照组和轻度、中度、重度NTG组受试者间均呈逐渐下降趋势。轻度NTG组患者黄斑区下方和颞侧区域RS均较对照组受试者降低。黄斑区各区域及整体平均RS随NTG病情分期加重而降低。在NTG组患者中,LD、PD与RS在黄斑区各区域和整体平均中均呈显著性正相关(均为P<0.05)。NTG组患者黄斑区LD、PD与P2在一定区域内呈正相关。结论 NTG患者黄斑区微循环状态及视功能均较健康人显著下降,且随病情进展而加重;NTG患者黄斑区血管密度与RS存在显著相关性。

基于V1区种子点应用静息态功能磁共振的功能连接技术分析正常眼压性青光眼患者脑部功能连接的变化

目的基于V1区种子点(ROI)应用静息态功能磁共振的功能连接技术研究正常眼压性青光眼(NTG)患者和健康志愿者的脑部功能连接变化,旨在探究NTG患者的发病机制及早期诊断方法。方法收集符合纳入标准的NTG患者14例(NTG组)及健康对照者14例(HCs组),收集受试者的临床数据信息后对两组受试者行静息态功能性磁共振成像扫描。通过软件对磁共振数据进行预处理,以双侧V1区作为ROI,分别计算其与全脑体素时间序列的相关性并比较组间静息态功能连接的差异得到V1区ROI和全脑的功能连接值。采用Pearson相关分析探讨NTG组患者与V1区功能连接显著差异脑区功能连接值与临床变量之间的相关性。结果与HCs组受试者相比,NTG组患者年龄、性别、体重、杯盘比、24 h平均眼压差异均无统计学意义(均为P>0.05),两组患者间左、右眼最佳矫正视力(BCVA)及视盘周围视网膜神经纤维层厚度(RNFLT)差异均有统计学意义(均为P<0.05)。Pearson相关性分析结果显示,NTG组患者与V1区异常功能连接脑区功能连接值均与RNFLT具有相关性(P<0.05)。ROI1-左侧额上回、ROI1-右侧额上回、ROI2-左侧扣带回和ROI2-右侧额中回与RNFLT均呈显著正相关(均为P<0.05)。与HCs组受试者相比,NTG组患者与右侧ROI功能连接减低的脑区为左侧额上回及右侧额上回;与左侧ROI功能连接减低的脑区为左侧扣带回和右侧额中回。结论相较于健康人,NTG患者某些特定大脑区域与V1区的功能连接有显著改变,包括双侧额上回、左侧扣带回、右侧额中回。大脑功能活动的变化区域可能由NTG引起的视觉功能障碍导致视觉和认知情绪处理脑区的功能损伤,这可能是NTG患者潜在神经病理机制之一。

Analysis of peripapillary retinal nerve fiber layer and inner macular layers by spectral-domain optical coherence tomography for detection of early glaucoma

AIM： To analyze the diagnostic capabilities of peripapillary retinal nerve fiber layer（p RNFL） thickness and segmented inner macular layer（IML） thickness measured by spectraldomain optical coherence tomography for detection of early glaucoma. METHODS： Fifty-three patients with primary open angle glaucoma（POAG）, 60 patients with normal tension glaucoma（NTG） and 32 normal control subjects were enrolled. Thicknesses of p RNFL, total macular layers（TML）, and the IML, including macular RNFL（m RNFL） and macular ganglion cell layer（m GCL） were assessed. The areas under the receiver operating characteristic curves（AROC） were calculated to compare the diagnostic power of different parameters. RESULTS： There were no differences in the parameters of p RNFL, TML, and IML between POAG and NTG groups. The thicknesses of superior and inferior m GCL showed significant correlation with mean deviation of visual field（R2=0.071, P=0.004; R2=0.08, P=0.002）. The m GCL thickness significantly correlated with the p RNFL thickness in the superior and inferior quadrants（R2=0.156, P〈0.001; R2=0.407, P〈0.001）. The thickness of the inferior-outer sector of macula had greater AROCs than those in the inferior-inner sector of macula. The AROCs for superior（0.894） and inferior（0.879） p RNFL thicknesses were similar with the AROCs for superior（0.839） and inferior m GCL（0.864） thicknesses. Sensitivities at 80% specificity for global p RNFL, inferior-outer m GCL and inferior-outer m RNFL thicknesses were 0.938, 0.867, and 0.725, respectively. CONCLUSION： The diagnostic capability of the m GCL thickness is comparable to that of the p RNFL thickness in patients with early glaucoma. The inferior-outer sector of IML has a better diagnostic capability than the inferiorinner sector of IML for detection of early glaucoma.

The Missing Piece in Glaucoma?

Glaucoma is defined as an optic disc neuropathy meaning the nerve fibers are being atrophied similar to the fate occurring in non-glaucomatous optic atrophies. Furthermore, the nerve fibers are always being destroyed randomly in all the non-glaucomatous optic atrophies. In contrast, the nerve fibers in glaucoma are invariably destroyed in an orderly tandem fashion, from peripheral to central, never randomly. Is glaucoma really an optic disc neuropathy in light of orderly destruction of nerve fibers in glaucoma? The current prevailing theories in glaucoma such as posterior bowing of the lamina cribrosa or cupping can’t explain the orderly destruction of nerve fibers occurring in glaucoma. In fact, there is no biological mechanism acting directly on the nerve fibers or their RGCs which could lead to their orderly destruction. Therefore, there should be some mechanical way, which could result in the orderly destruction of nerve fibers even though this mechanical scenario may have resulted from the direct biological effect of raised IOP on some important component of the optic disc. It is proposed that the border tissue of Elschnig (BT) atrophies due to chronic ischemia caused by raised IOP, and as a result, the lamina cribrosa (LC) begins sinking in the scleral canal—a mechanical problem. Due to sinking of the LC, the nerve fibers get stretched and broken starting with the most peripheral nerve fibers being closest to the edge of the scleral opening and ending with the most central nerve fibers in an orderly tandem fashion. Therefore, in view of the orderly destruction of nerve fibers, glaucoma may not be an optic disc neuropathy but an optic disc axotomy.

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.

Corneal Biomechanical Parameters and Asymmetric Visual Field Damage in Patients with Untreated Normal Tension Glaucoma

Background： High intraocular pressure （IOP） and low central corneal thickness （CCT） are important validated risk factors for glaucoma, and some studies also have suggested that eyes with more deformable corneas may be in higher risk of the development and worsening of glaucoma. In the present study, we aimed to evaluate the association between corneal biomechanical parameters and asymmetric visual field （VF） damage using a Corvis-ST device in patients with untreated normal tension glaucoma （NTG）. Methods： In this observational, cross-sectional study, 44 newly diagnosed NTG patients were enrolled. Of these, 31 had asymmetric VF damage, which was defined as a 5-point difference between the eyes according to the Advanced Glaucoma Intervention Study scoring system. Corneal biomechanical parameters were obtained using a Corvis-ST device, such as time from start until the first and second applanation is reached （time A 1 and time A2, respectively）, cord length of the first and second applanation （length A 1 and length A2, respectively）, corneal speed during the first and second applanation （velocity A1 and velocity A2, respectively）, time from start until highest concavity is reached （time HC）, maximum amplitude at the apex of highest concavity （def ampl HC）, distance between the two peaks at highest concavity （peak dist HC）, and central concave curvature at its highest concavity （radius HC）. Results： Time A 1 （7.19 q- 0.28 vs. 7.37 ~ 0.41 ms, P = 0.010）, length A 1 （1.73 [ 1.70-1.76] vs. 1.78 [ 1.76-1.79] mm, P = 0.007）, length A2 （1.58 [1.46-1.70] vs. 1.84 [h76-1.92] mm, P 〈 0.001）, peak dist HC （3.53 [3.08-4.00] vs. 4.33 [3.92-4.74] mm, P = 0.010）, and radius HC （6.20 ± 0.69 vs. 6.59 i h 18 mm, P = 0.032） were significantly lower in the worse eyes than in the better eyes, whereas velocity A 1 and def ampl HC were significantly higher （0.156 [0.149-0.163] vs. 0.145 [0.138-0.152] m/s, P= 0.002 and 1.19 ± 0.13 vs. 1.15 ± 0.13 mm, P = 0.005, respectively）. There was no significant difference in time A2, velocity A2, and time HC between the two groups. In addition, no difference was observed in lOP, CCT, and axial length. In the univariate and multivariate analyses, some of the Corvis-ST parameters, including time A1 and def ampl HC, were correlated with known risk factors for glaucoma, and there was also a significant positive correlation between def ampl HC and age. Conclusions： There were differences in dynamic corneal response parameters but not IOP or CCT between the paired eyes of NTG patients with asymmetric VF damage. We suggest that the shape of the cornea is more easily altered in the worse eyes of asymmetric NTG patients.

Comparison of corneal biomechanics among primary open-angle glaucoma with normal tension or hypertension and controls

Background:Normal tension glaucoma(NTG)is a less pressure-dependent type of glaucoma with characteristic optic neuropathy.Recently,the biomechanical mechanism has been thought to account for glaucomatous optic neuropathy to some degree.We intended to compare dynamic corneal response parameters(DCRs)among patients with primary open-angle glaucoma with normal tension or hypertension and controls.The correlations between DCRs and known risk factors for glaucoma were also analyzed.Methods:In this cross-sectional study,49 NTG subjects,45 hypertension glaucoma(HTG)subjects,and 50 control subjects were enrolled.We compared the differences in DCRs using corneal visualization Scheimpflug technology among the NTG,HTG,and control groups.We also analyzed the correlations between DCRs and known risk factors for glaucoma(eg,central corneal thickness[CCT],intraocular pressure[IOP],etc).Results:The maximum inverse concave radius(NTG:0.18[0.17,0.20]mm-1;control:0.17[0.16,0.18]mm-1;P=0.033),deformation amplitude ratio of 2 mm(DAR 2 mm,NTG:4.87[4.33,5.39];control:4.37[4.07,4.88];P<0.001),and DAR 1 mm(NTG:1.62[1.58,1.65];control:1.58[1.54,1.61];P<0.001)were significantly higher in NTG than in the controls.The integrated radius(IR,NTG:8.40±1.07 mm-1;HTG:7.64±1.31 mm-1;P=0.026)and DAR 2 mm(NTG:4.87[4.33,5.39];HTG:4.44[4.12,5.02];P<0.007)were significantly higher,whereas the stiffness parameter at the first applanation(SP-A1,NTG:91.23[77.45,107.45];HTG:102.36[85.77,125.12];P=0.007)was lower in NTG than in HTG.There were no significant differences in the DCRs between HTG and control groups(P>0.05).In the univariate and multivariate analyses,some of the DCRs,such as IR,were negatively correlated with CCT and IOP,whereas SP-A1 was positively correlated with CCT and IOP.Conclusions:The cornea was more deformable in NTG than in HTG or controls.There were no significant differences in corneal deformability between HTG and controls.The cornea was more deformable with the thinner cornea and lower IOP.

正常眼压性青光眼患者黄斑区血流灌注状态与视野缺损的相关性研究

目的观察正常眼压性青光眼(NTG)患者黄斑区血流灌注状态,分析其与视野缺损之间的相关性。方法纳入2020年1月—2021年2月就诊于上海中医药大学附属曙光医院的符合纳入标准的NTG患者70例(70只眼)作为观察组,选取同期同医院就诊的同年龄段的健康志愿者49例(49只眼)作为对照组。采集受试者黄斑区视网膜浅层血管线性密度(MSRVLD)、黄斑区视网膜浅层血管灌注密度(MSRPD)、黄斑中心凹无血管区面积(FAZ)及观察组患者的视野平均缺损(MD),并对以上数据进行统计学分析。结果(1)MSRVLD:观察组黄斑区下方及鼻侧较对照组下降,差异均有统计学意义(t_(下方)=4.041,P=0.000;t_(鼻侧)=2.945,P=0.004)。(2)MSRPD:观察组黄斑区下方及鼻侧较对照组下降,差异均有统计学意义(t_(下方)=3.291,P=0.001;t_(鼻侧)=2.924,P=0.004)。(3)黄斑中心凹FAZ:观察组黄斑中心凹FAZ面积为(0.21±0.13)mm^(2),对照组为(0.23±0.17)mm^(2)。2组比较,差异无统计学意义(P>0.05)。(4)相关性分析:观察组MD与MSRVLD、MSRPD呈正相关(r_(MSRVLD)=0.387,r_(MSRPD)=0.402,均P=0.001)。结论NTG患者黄斑区存在血流灌注不足,且与MD相关。

正常眼压性青光眼患者认知功能损害及相关因素分析

目的探讨正常眼压性青光眼(NTG)患者认知功能损害发生情况及相关影响因素。方法选取2011年6月—2014年1月在北京大学第三医院眼科门诊就诊的NTG患者41例,记录其一般资料,并进行汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)、匹兹堡睡眠质量指数(PSQI)、蒙特利尔认知评估量表(Mo CA)等检测。结果根据Mo CA量表检测结果,将患者分为伴认知功能损害组(27例)和不伴认知功能损害组(14例)。认知功能损害发生率为65.8%(27/41)。两组患者性别、吸烟、饮酒、文化程度、睡眠障碍史、失眠家族史、打鼾、高脂血症、糖尿病、冠心病、脑血管疾病、胃肠道疾病、焦虑、抑郁发生率比较,差异均无统计学意义(P>0.05);两组患者年龄、BMI、高血压、睡眠障碍发生率比较,差异有统计学意义(P<0.05)。Logistic回归分析结果显示,年龄、BMI及PSQI是NTG伴认知功能损害的危险因素(P<0.05)。NTG伴认知功能损害患者Mo CA总分为(22.5±2.4)分,各项目评分较参考值下降程度比较,差异有统计学意义(F=17.99,P<0.05),其中记忆功能评分较参考值下降程度均高于其他项目评分较参考值下降程度(P<0.05)。将各项目评分较参考值下降程度与年龄、PSQI、BMI进行相关分析,结果显示,各项目评分较参考值下降程度与年龄均无直线相关关系(r=0.219、0.172、0.008、0.046、0.349、-0.137、0.118、0,P>0.05);记忆功能、视空间功能、执行功能、注意力、语言功能、时间定向力、地点定向力与PSQI均无直线相关性(r=0.141、0.171、-0.035、-0.027、-0.093、-0.275、0,P>0.05),计算力、注意力和短期记忆力与PSQI呈正相关(r=0.410,P=0.042);记忆功能、视空间功能、执行功能、注意力、语言功能、时间定向力、地点定向力与BMI均无直线相关性(r=0.042、-0.011、0.192、0.038、0.168、-0.141、0,P>0.05),计算力、注意力和短期记忆力与BMI呈正相关(r=0.432,P=0.031)。结论 NTG伴认知功能损害发生率较高,增龄、睡眠障碍和肥胖可增加NTG患者伴发认知功能损害的风险,并以记忆功能损害更为显著。