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International Journal of Ophthalmology(English edition) 2024年第3期17卷 509-517页

作者： Umay Güvenç Gülizar Demirok Güner Üney Selma Uzman Ophthalmology Department Ankara Training and Research HospitalAnkara 06230Turkey

●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.

关键词： normal tension glaucoma neuroimaging atypical visual field defects

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

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World Journal of Cardiology 2024年第1期16卷 10-15页

作者： Prasanna Venkatesh Ramesh Arvind Kumar Morya Ajanya K Aradhya Pavithra Pannerselvam Sai Thaejesvi Gopalakrishnan Shruthy Vaishali Ramesh Aji Kunnath Devadas Navaneeth Krishna Department of glaucoma and Research Mahathma Eye Hospital Private LimitedTrichy 620017Tamil NaduIndia Department of Ophthalmology All India Institute of Medical SciencesHyderabad 508126TelanganaIndia Department of Optometry and Visual Science Mahathma Eye Hospital Private LimitedTrichy 620017Tamil NaduIndia Mahathma Eye Hospital Private Limited Trichy 620017Tamil NaduIndia Department of Cataract and Refractive Surgery Mahathma Eye Hospital Private LimitedTrichy 620017Tamil NaduIndia

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.

关键词： normal tension glaucoma Vascular dysregulation Ocular blood flow Blood pressure Perfusion pressure Oxidative stress

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

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Neural Regeneration Research 2023年第1期18卷 87-93页

作者： Wen-Cui Shen Bing-Qing Huang Jin Yang Tianjin Eye Hospital&Eye Institute Tianjin Key Laboratory of Ophthalmology and Visual ScienceNankai UniversityTianjinChina State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinChina

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.

关键词： autophagy endothelin 1 glutamate neurotoxicity inhibitor nerve regeneration neuroinflammation normal tension glaucoma oxidative stress retinal ganglion cell vasoconstriction

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Corneal Biomechanical Parameters and Asymmetric Visual Field Damage in Patients with Untreated normal tension glaucoma

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Chinese Medical Journal 2017年第3期130卷 334-339页

作者： Bai-Bing Li Yu Cai Ying-Zi Pan Mei Li Rong-Hua Qiao Yuan Fang Tian Tian Department of Ophthalmology Peking University First Hospital Key Laboratory of Vision Loss and Restoration Ministry of Education Beijing 100034 China Department of Ophthalmology Beijing Tsinghua Changgung Hospital Beijing 102218 China

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

关键词： Asymmetric Visual Field Damage Corneal Biomechanical Parameters Corvis-ST normal tension glaucoma Untreated

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

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International Journal of Ophthalmology(English edition) 2018年第8期11卷 1342-1351页

作者： Pei-Wen Lin Hsueh-Wen Chang Ing-Chou Lai Jen-Chia Tsai Yi-Chieh Poon Department of Ophthalmology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Department of Biological Sciences Sun Yat-Sen University

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 capabi

关键词： retinal nerve fiber layer macular thickness primary open angle glaucoma normal tension glaucoma hemisphere retinal asymmetry optical coherence tomography

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

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International Journal of Ophthalmology(English edition) 2015年第3期8卷 476-483页

作者： Man Yu Bo Chen Bo Gong Ping Shuai Zheng-Zheng Wu Wei Lin Department of Ophthalmology Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Sichuan Key Laboratory for Human Disease Gene Study Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Center of Health Physical Examination and Health Management Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital

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.

关键词： normal tension glaucoma polyunsaturated fatty acid erythrocytes plasma

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

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International Journal of Ophthalmology(English edition) 2020年第1期13卷 71-78页

作者： Xiao-Yu Xu Kun-Bei Lai Hui Xiao Yi-Quan Lin Xin-Xing Guo Xing Liu State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat-sen University

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.

关键词： normal tension glaucoma primary open angle glaucoma spectral domain optical coherence tomography ganglion cell-inner plexiform layer thickness pattern

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

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Chinese Medical Journal 2021年第9期134卷 1087-1092页

作者： Ya-Hui Wei Yu Cai Bonnie N.K.Choy Bai-Bing Li Ruo-Shi Li Chen Xing Xia Wang Tian Tian Yuan Fang Mei Li Ying-Zi Pan Department of Ophthalmology Peking University First HospitalBeijing 100034China Department of Ophthalmology LKS Faculty of MedicineThe University of Hong KongHong KongChina Department of Ophthalmology Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China

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];P0.05).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.

关键词： Corneal biomechanics Primary open-angle glaucoma normal tension glaucoma Hypertensive glaucoma

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The Comparison Study of Renin and Angiotensin AⅡ Levels on normal tension glaucoma Patients and normal Individuals

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眼科学报 2005年第3期 64-67页

作者： Hongmin Yun, Pei Fu, Kexi Ding, Qi Yang Department of Ophthalmology, Peking University Shenzhen Hospital, Shenzhen 518036, China

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.

关键词： normal tension glaucoma renin angiotensin AⅡ renin-angiotension system

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

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International Journal of Ophthalmology(English edition) 2018年第7期11卷 1163-1172页

作者： Pei-Wen Lin Hsueh-Wen Chang Jih-Pin Lin Ing-Chou Lai Department of Ophthalmology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Department of Biological Sciences Sun Yat-Sen University

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.

关键词： retinal nerve fiber layer ganglion cell layer primary open angle glaucoma normal tension glaucoma optical coherence tomography