Sera of glaucoma patients show autoantibodies against myelin basic protein and complex autoantibody profiles against human optic nerve antigens

Background The aim of this study was to gain more information about the possible immunological mechanisms in glaucoma. We analyzed the complex autoantibody patterns against human optic nerve antigens in sera of patients with glaucoma and tried to identify important antigens. Methods Sera of 133 patients were included: healthy control subjects (n = 44), primary open-angle glaucoma (n = 44), and normal tension glaucoma patients (n = 45). The sera were tested against Western blots of human optic nerve, and antibody bands were visualized with chloronaphthol. IgG antibody patterns were analyzed by multivariate statistical techniques, and the most significant antigens were identified by mass spectrometry (Maldi-TOFTOF). Results All subjects, even healthy ones, showed different and complex antibody patterns. Glaucoma groups showed specific up- and down-regulations of antibody reactivities compared to the control group. The multivariate analysis of discriminance found significant differences (P < 0.05) in IgG antibody profiles against human optic nerve antigens between both glaucoma groups and healthy subjects. The identified antigens include: myelin basic protein (up-regulated in the POAG group), glial fibrillary acidic protein (down-regulated in the glaucoma groups), and vimentin (down-regulated in the glaucoma groups in comparison to controls). Conclusions Using human optic nerve antigen, we were able to demonstrate that complex IgG autoantibody patterns exist in sera of patients with glaucoma. Large correlations between the given and our previous studies using bovine optic nerve antigens could be seen. Furthermore, anti-myelin basic protein antibodies, which can also be detected in patients with multiple sclerosis, were found in sera of glaucoma patients.     

Analysis of autoantibody repertoires in sera of patients with glaucoma

PURPOSE: Glaucoma is the second cause of blindness worldwide. It is usually considered a neurodegenerative disease. There is evidence that an autoimmune mechanism is involved in the development of glaucoma in some patients. The aim of this study was to analyze the IgG autoantibody repertoires in sera of glaucoma patients and healthy subjects. METHODS: A total of 82 patients were divided into four groups: healthy volunteers without any ocular disorders (CO, n = 30), patients with primary open-angle glaucoma (POAG, n = 19), ocular hypertension (OHT, n = 16), and normal tension glaucoma (NTG, n = 17). All groups were matched for age and gender. The sera of these patients were tested against Western blots of retinal antigens. Immunodetection was done using 4-chloro-1-naphthol staining. The autoantibody patterns were digitized and subsequently analyzed by multivariate statistical techniques. RESULTS: All patients showed different, complex staining patterns of autoantibodies against retinal antigens. There was an increase in the number of peaks in sera of patients with primary open-angle glaucoma (POAG) compared to healthy subjects (CO). Including all peaks the analysis of discriminance revealed a statistically significant difference between the patterns of POAG compared to all other groups (p < 0.01). Sera of normal tension glaucoma (NTG) had no statistically different autoantibody pattern compared to those of control subjects. CONCLUSIONS: In this study, we demonstrated a difference in the IgG autoantibody patterns of primary open-angle glaucoma patients compared to healthy subjects. However, the patterns were not significantly different in normal tension glaucoma compared to control subjects.     

Fluorescein filling defects of the optic nerve head in normal tension glaucoma, primary open-angle glaucoma, ocular hypertension and healthy controls

BACKGROUND: To evaluate fluorescein filling defects of the optic nerve head in normal tension glaucoma (NTG), primary open-angle glaucoma (POAG), ocular hypertension (OHT) and controls. METHODS: Forty patients with NTG (mean age 55 +/- 10 years), 40 patients with POAG (mean age 55 +/- 11 years), 40 patients with OHT (mean age 53 +/- 13 years), and 40 age-matched controls (mean age 54 +/- 11 years) were included in a prospective study. Video fluorescein angiograms were performed by means of a scanning laser ophthalmoscope. The extent of absolute filling defects of the optic nerve head was assessed (as a percentage of the disc area) using digital image analysis. Visual fields were tested by automatic static perimetry (Humphrey Field Analyzer, programme 24-2). RESULTS: Absolute filling defects were significantly larger in patients with NTG (12.2 +/- 15.5%) and POAG (12.9 +/- 13.1%) compared to patients with OHT (1.2 +/- 3.6%) and healthy controls (0.1 +/- 0.5%) (p < 0.0001). The area under the receiver operating characteristic (ROC) curve was 0.806 for NTG vs healthy controls, and 0.812 for POAG vs OHT. Absolute filling defects are significantly correlated to the global indices mean deviation (r = -0.63, p < 0.0001), pattern standard deviation (r = 0.61, p < 0.0001), and corrected pattern standard deviation (r = 0.62, p < 0.0001) and significantly correlated to horizontal (r = 0.50, p < 0.0001) and vertical (r = 0.53, p < 0.0001) cup-to-disc-ratios. CONCLUSIONS: Fluorescein filling defects of the optic disc representing capillary dropout are present in NTG and POAG. The extent of these filling defects is correlated to visual field loss and morphological damage. Fluorescein angiography may be useful in the diagnosis and management of NTG and POAG.     

Absolute filling defects of the optic disc in fluorescein angiograms in glaucoma--a retrospective clinical study

BACKGROUND: Analysis of clinical importance of the size of filling defects in fluorescein angiograms in primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), ocular hypertension and subjects with physiological excavations in comparison to visual field loss, optic nerve head morphology and hemodynamics. PATIENTS AND METHODS: 75 patients (POAG, NTG, ocular hypertension) and 10 healthy subjects with physiological excavations were included in this study. In digitized video fluorescein angiograms (Scanning Laser Ophthalmoscope) the size of absolute filling defects of the optic disc was quantified in the early venous phase and expressed by percentage of the optic disc. Visual fields were obtained by conventional static perimetry (Humphrey 24-2) and graded in stages of glaucoma visual field defects (Aulhorn I-V). Optic disc excavations were evaluated as cup-to-disc-area-ratios. RESULTS: The filling defects correlated with the visual-field loss stages of Aulhorn and the visual field indices MD (mean deviation), PSD (pattern standard deviation) and CPSD (corrected pattern standard deviation). There was no correlation with the index SF (short-term fluctuation) and with systemic hemodynamics (blood pressure, perfusion pressure) or the IOP. Absolute filling defects correlated with the cup-to-disc-area-ratio in NTG. The absolute filling defects were larger in patients with glaucoma (POAG, NTG) in comparison to patients without glaucomatous visual field loss (ocular hypertension, glaucoma-like discs). No difference of filling defects was found in the glaucoma group (POAG, NTG). Patients with NTG had larger excavations and lower systolic blood pressures than patients with POAG. CONCLUSION: The size of fluorescein filling defects may be useful as a parameter for the evaluation of an ischemic lesion of the optic nerve head. Absolute filling defects may differentiate POAG from ocular hypertension and NTG from glaucoma-like discs without field defects. The results support the hypothesis that in POAG and NTG disturbances of the circulation result in similar filling defects of the optic disc and visual field loss.     

The optic nerve head in normal-tension glaucoma

There is controversy over the definition, appearance, and characteristics of the optic nerve head in normal-tension glaucoma (NTG). Optic disk size is greater in eyes with NTG than in those with primary open-angle glaucoma. However, in an intraindividual bilateral comparison, the eye with the larger optic disk showed neither more marked nor less pronounced glaucomatous optic nerve damage. Optic disk hemorrhage and peripapillary atrophy have been reported to be more frequent in patients with NTG. Nonuse of calcium channel blockers, peripapillary atrophy, and disk hemorrhage were statistically significantly associated with visual field loss progression in NTG. However, there is a possibility that a high IOP may stop disk hemorrhage relatively early. Histopathologic optic nerve head changes correlated with the clinical appearance of the optic nerve head, which is comparable in NTG and primary open-angle glaucoma. However, as novel findings, serum antibodies to retinal proteins and retinal immunoglobulin deposition in the ganglion cells were observed, and the level of serum autoantibodies to optic nerve head glycosaminoglycans was higher in patients with NTG than in patients with primary open-angle glaucoma.     

高眼压性和正常眼压性原发性开角型青光眼视神经损害特征的比较

目的探讨高眼压性原发性开角型青光眼(POAG)和正常眼压性青光眼(NTG)患者视神经损害的不同特点。方法应用德国Heidelberg公司生产的视网膜断层扫描仪对高眼压性POAG39例(47只眼)和NTG32例(38只眼)进行定量视盘参数和神经纤维层检查,并行眼底立体照相观察视网膜神经纤维层(RNFL)缺损类型,检测静态定量视野,并对检查结果进行比较。结果(1)NTG组视盘总体参数和分区(除颞侧外)盘沿面积、沿/盘面积小于高眼压性POAG组,而C/D大于高眼压性POAG组;平均RNFL厚度和RNFL面积在颞下和颞上小于高眼压性POAG组;总体盘沿容积小于高眼压性POAG组,总体平均视杯深度和颞下视杯面积大于高眼压性POAG组,两组差异均有统计学意义(P<005)。两组颞侧视盘各参数比较,差异无统计学意义(P>005)。(2)RNFL缺损类型高眼压性POAG组RNFL弥漫性缺损占5319%,局限性缺损占426%;NTG组弥漫性缺损占2105%,局限性缺损占5526%。两组RNFL缺损类型构成比比较,差异有统计学意义(P<001)。结论NTG较高眼压性POAG具有较大的C/D值、C/D面积比和窄盘沿面积,RNFL丢失严重。高眼压性POAG患者的RNFL以弥漫性缺损为主,NTG患者的RNFL以局限性缺损为主。两者视神经损害具有不同特点,其损害机制可能不同。(中华眼科杂志,2005,41136140)     

Lower corneal hysteresis in glaucoma patients with acquired pit of the optic nerve (APON)

Objective Acquired pit-like changes of the optic nerve head (APON) are characteristic of glaucomatous damage and may be a sign of a localized susceptibility of the optic nerve. Thus, it is possible that biomechanical properties of the ocular tissues may play a pressure-independent role in the pathogenesis of glaucoma. Corneal hysteresis (CH) appears to provide information of the biomechanical properties of the ocular hull tissues. The purpose of this study was to compare CH of patients with primary open angle glaucoma (POAG) with and without APON. Methods A prospective case control study was done. POAG patients with and without APON were measured using the Ocular Response Analyzer by masked investigators. Patients in both groups were matched for sex, age, corneal thickness, and type of glaucoma according to maximal IOP (NTG or POAG). Statistical analysis was done using ANOVA. Results Corneal hysteresis of 16 glaucomatous eyes with APON and 32 controls (glaucoma without APON) was measured. The mean (±SD) CH in the APON group was 8.89 (±1.53) and 10.2 (±1.05) in the control group. The difference is statistically significant (p = 0.005). Conclusions Corneal hysteresis in POAG patients with APON was significantly lower than in patients that did not have such structural changes of the optic disc. These findings may reflect pressure-independent mechanisms involved in the pathogenesis of such glaucomatous optic nerve changes.     

Relationship between optic nerve head microcirculation and visual field loss in glaucoma

PURPOSE: To study the relationship between optic nerve head blood flow velocity and visual field loss in patients with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). METHODS: This study included 44 eyes of 44 patients with POAG and 44 eyes of 44 patients with NTG. To evaluate optic nerve head blood flow velocity, the square blur rate (SBR) was measured by means of laser speckle flowgraphy. The correlation between SBR and Humphrey visual field indices was evaluated with linear regression analysis. RESULTS: In the NTG group, the average SBR at the superior and inferior temporal neuroretinal rim was positively correlated with mean deviation (MD) (r = 0.349, p = 0.020). The SBR at the superior or inferior temporal neuroretinal rim was positively correlated with the sum of the total deviations in the corresponding hemifields (r = 0.299, p = 0.049; r = 0.354, p = 0.019, respectively). The correlations between SBR and MD did not differ statistically between the NTG and POAG groups; however, no significant correlation between SBR and visual field indices was observed in the POAG group. CONCLUSION: These results suggested that the change in the circulation of the optic nerve head may be related to visual field damage in the NTG group but may be less involved in visual field damage in the POAG group.     

Fluorescein leakage of the optic disc in glaucomatous optic neuropathy

Purpose To identify and quantify the role of capillary leakage of the optic nerve head in digital fluorescein angiography in normal subjects and patients with open-angle glaucoma.Methods We conducted a prospective cross-sectional study in the Department of Ophthalmology of the Technical University of Aachen. Thirty patients with primary open-angle glaucoma (POAG) and 30 healthy age-matched subjects were included. Fluorescein angiograms were performed using the scanning laser ophthalmoscope. The fluorescence of the optic nerve head and the surrounding retina (ratio of leakage) was measured using digital imaging analysis in the late phases of the angiogram (9–10 min).Results The ratio of optic nerve head fluorescence to retinal reference loci was significantly increased (p=0.01) in patients with glaucoma (POAG, 1.38±0.34) compared with normal subjects (1.20±0.19). Intraocular pressure (p=0.0001), visual field indices (mean deviation, p<0.0001; pattern standard deviation, p<0.0001; corrected pattern standard deviation, p<0.0001), and cup to disc ratios (p=0.02) differed significantly between the groups. Age and systolic and diastolic blood pressure showed no significant differences between groups.Conclusion Fluorescein angiography revealed significantly increased vascular leakage of glaucomatous optic nerve heads. An endothelial disruption and fluorescein leakage might be the result of mechanical stress at the level of the lamina cribrosa and/or a sign of ischemic damage. This measurement approach might enable us to judge the severity of optic nerve head leakage, and it is a potential way to evaluate therapeutic regimens.     

Retinal ganglion cells recognized by serum autoantibody against gamma-enolase found in glaucoma patients

PURPOSE: To study pathologic roles of the presence of serum autoantibodies against retinal ganglion cells in patients with glaucoma. METHODS: Serum autoantibody reactions were detected by Western blot analysis using retinal soluble fractions in 79 patients with glaucoma (normal-tension glaucoma [NTG], 23 cases; primary open-angle glaucoma [POAG], 56 cases) and 60 age-matched healthy subjects. Clinical characteristics including visual acuity, visual field, intraocular pressure (IOP), and optic disc features were compared between the serum autoantibody-positive and -negative patients. The retinal autoantigen recognized by patients' sera was identified by a combination of in-gel digestion and Edman sequencing. RESULTS: Western blot analysis revealed that serum autoantibody against retinal 50-kDa antigen was recognized in 20 out of 79 glaucoma patients (25.3%; 14 POAG and 6 NTG patients) and 60 age-matched control subjects (11.7%), respectively. Immunocytochemistry revealed that labeling of the ganglion cell layer (GCL) by IgG from glaucoma patients (POAG: 13/56, 23.2%; NTG: 6/23, 26%) existed at a significantly higher rate than that by IgG from control subjects (2/60, 3.3%; P < 0.05). In POAG, maximum IOP in the serum antibody positive-patients was significantly lower than that in the antibody-negative patients (P < 0.05). However, no statistical differences were observed in visual field loss, disc cupping, and other clinical factors between the antibody-positive and -negative groups in POAG and NTG. In-gel digestion of the 50-kDa band in two-dimensional polyacrylamide gels and Edman sequence analysis of the high-performance liquid chromatography-purified peptides identified the 50-kDa protein as gamma-enolase. Injection of the 50-kDa IgG from glaucoma patients or anti-gamma-enolase serum into the vitreous cavity of Lewis rats caused reduction of the b-wave of the electroretinogram and TdT-dUTP terminal nick-end labeling (TUNEL)-positive staining within the GCL. CONCLUSIONS: In the current study, serum autoantibody against 50-kDa protein identified as gamma-enolase in 25% of glaucoma patients.     

眼灌注压对人视乳头微循环的影响

目的 了解眼外负压吸引诱导的眼灌注压改变的条件下，正常人、原发性开角性青光眼(POAG)患者和正常眼压性青光眼患者(NTG)的视乳头微循环的变化，探讨视乳头局部自身调节的幅度。方法正常人8例，POAG患者10例和NTG患者7例，采用眼外负压杯吸引诱导眼压升高，负压增加的幅度为30s50mmHg，同时测量眼压。采用HRF测量视乳头处血流量。将基础状态下视乳头血流值作为基础值，当眼压升高到30mmHg和40mmHg时，分别测量这两点视乳头微循环的血流值，在40mmHg后解除负压吸引，测量负压吸引解除后1min、5min时视乳头微循环的血流值。结果 三组视乳头的基础血流量无明显差异。当眼压升高到30mmHg时，正常组的血流量仍维持稳定，但POAG组和NTG组明显下降，POAG组下降幅度超过25％，NTG组下降幅度超过45％。当眼压升高到40mmHg，正常组视乳头血流量也出现明显下降，其中0NHF下降约30％，POAG组和NTG组下降更明显，POAG组下降幅度超过50％，NTG组下降幅度超过65％。在解除负压吸引后1min，正常组血流量增加的幅度约为31％，POAG组增加约19％，NTG组无明显增加。在负压解除后5min，三组视乳头血流基本恢复到基础状态。结论 正常组视乳头微循环有一定范围的自身调节幅度，可以耐受眼灌注压一定程度的改变，POAG组和NTG组自身调节能力均有不同程度的损害。     

Serum autoantibodies to alpha-fodrin are present in glaucoma patients from Germany and the United States

PURPOSE: Glaucoma is characterized by a progressive loss of retinal ganglion cells that results in a characteristic optic neuropathy associated with visual field loss. In previous studies, changes in the antibody profiles have been shown in the sera of patients with glaucoma, and these findings suggest a role for autoimmune involvement in the pathogenesis of glaucoma in some patients. The purpose of this study was to compare the antibody profiles against optic nerve antigens in patients with glaucoma in two different study populations from Germany and the United States. METHODS: One hundred twenty patients were included in the study, 60 from Germany and 60 from the United States: a control group (CTRL, n = 20), a group of patients with primary open-angle glaucoma (POAG, n = 20), and one group of patients with normal-pressure glaucoma (NPG, n = 20) from each country. Western blot analyses against bovine optic nerve antigens were used to detect the IgG antibody patterns present in the patients' sera. The complex antibody profiles were analyzed by multivariate statistical techniques. RESULTS: Complex IgG autoantibody repertoires were present in all patients with glaucoma as well as healthy subjects from both the German and the United States study population. A large similarity between all antibody profiles in both study populations was demonstrated in the number and frequency of both up- and downregulation of antibody reactivities in patients with glaucoma of both national cohorts. The multivariate analysis of discriminance found a significant difference between the glaucoma groups and healthy subjects against optic nerve antigens. As in previous studies, the NPG group revealed the highest variance from the control group (P < 0.01). Furthermore, a newly described antibody biomarker in both study populations was identified as alpha-fodrin. Western blot results revealed that there was an increased frequency and enhanced immunoreactivity to alpha-fodrin (120 kDa) in the sera of patients with NPG. The presence of alpha-fodrin autoantibodies were confirmed by ELISA, in which a highly elevated anti-alpha-fodrin titer in patients with NPG was found to be significantly greater than in the control subjects (P < 0.01) or age-matched patients with POAG (P < 0.04). CONCLUSIONS: Complex IgG antibody patterns against optic nerve antigens can be reproducibly identified in the serum of study populations from the United States and Germany. In both cohorts, patients with glaucoma have characteristic differences in serum autoantibody repertoires from those in control subjects. A newly described autoantibody to alpha-fodrin found in other neurodegenerative diseases such as Alzheimer's, further implicate a role for autoimmunity and the neurodegenerative processes in glaucoma. The high correspondence of the autoantibody patterns found in the study populations from different continents provides further evidence that serum autoantibody patterns may be useful biomarkers for glaucoma detection or for determining prognosis in future studies by means of pattern-matching algorithms.     

A comparison of optic disc topographic parameters in patients with primary open angle glaucoma,normal tension glaucoma,and ocular hypertension

Background Heidelberg Retina Tomograph (HRT) findings have been employed to quantitatively assess the topography of optic discs. We measured topographic parameters of optic discs in patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and ocular hypertension (OH) using an HRT in order to determine whether HRT topographic parameters can be used to differentiate those conditions.Methods Seventeen eyes in 17 patients with POAG, 23 eyes in 23 patients with NTG, and 15 eyes in 15 patients with OH were examined using an HRT, and the results were analyzed by age, refractive error, and topographic parameters.Results Among the HRT parameters, the mean values for rim area, rim volume, cup disk area ratio, and classification showed significant differences among POAG, NTG, and OH eyes. The mean values for cup area, cup volume, mean RNFL thickness, and RNFL cross section area showed significant differences between POAG and NTG eyes, and NTG and OH eyes, however, not between POAG and OH eyes. Cup shape measure showed significant differences between POAG and OH, and NTG and OH eyes, but not between POAG and NTG eyes.Conclusions Our results suggest that POAG is distinguishable from NTG and OH based on evaluations of rim area and rim volume. Patients with NTG tend to have larger cupping, smaller rims, and thinner retinal nerve fiber layers as compared to POAG and OH patients. Thus, HRT topographic parameters are useful to differentiate patients with POAG, NTG, and OH.     

Intraocular pressure correlates with optic nerve sheath diameter in patients with normal tension glaucoma

Purpose

1. Identify differences in optic nerve sheath diameter (ONSD) as an indirect measure of intracranial pressure (ICP) in glaucoma patients and a healthy population. 2. Identify variables that may correlate with ONSD in primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) patients.

Methods

Patients with NTG (n?=?46) and POAG (n?=?61), and healthy controls (n?=?42) underwent B-scan ultrasound measurement of ONSD by an observer masked to the patient diagnosis. Intraocular pressure (IOP) was measured in all groups, with additional central corneal thickness (CCT) and visual field defect measurements in glaucomatous patients. Only one eye per patient was selected. Kruskal–Wallis or Mann–Whitney were used to compare the different variables between the diagnostic groups. Spearman correlations were used to explore relationships among these variables.

Results

ONSD was not significantly different between healthy, NTG and POAG patients (6.09?±?0.78, 6.03?±?0.69, and 5.71?±?0.83 respectively; p?=?0.08). Visual field damage and CCT were not correlated with ONSD in either of the glaucoma groups (POAG, p?=?0.31 and 0.44; NTG, p?=?0.48 and 0.90 respectively). However, ONSD did correlate with IOP in NTG patients (r?=?0.53, p?<?0.001), while it did not in POAG patients and healthy controls (p?=?0.86, p?=?0.46 respectively). Patient’s age did not relate to ONSD in any of the groups (p?>?0.25 in all groups).

Conclusions

Indirect measurements of ICP by ultrasound assessment of the ONSD may provide further insights into the retrolaminar pressure component in glaucoma. The correlation of ONSD with IOP solely in NTG patients suggests that the translaminar pressure gradient may be of particular importance in this type of glaucoma.     

Scanning laser polarimetry, retinal nerve fiber layer photography, and perimetry in the diagnosis of glaucomatous nerve fiber defects

Background: Retinal nerve fiber layer defects are part of early glaucomatous damage. In the present study, we compared the ability of retinal nerve fiber layer photography (NFP) and scanning laser polarimetry (SLP) to detect nerve fiber layer defects in glaucoma patients. Methods: Besides ophthalmological standard examinations, we performed NFP (Zeiss Ikon fundus camera 30°, green filter), SLP (GDx, 1.0.14 and 2.0.09, LDT) and automated perimetry (Oculus, Twinfield, 30°) in 150 glaucoma patients [74 with primary open-angle glaucoma (POAG) and 76 with normal-tension glaucoma (NTG)]. The perimetric results were evaluated according to a modified Aulhorn classification. NFP and SLP were graded according to Quigley. Results: In POAG, 42% of NFP and 5% of SLP were not evaluable. In NTG, 24% of NFP and 4% of SLP were not evaluable. In POAG, NFP and SLP revealed a direct agreement in 54.5%, and in NTG, 55%; there was a small dif-ference of one stage in 39.5% (POAG) and 41% (NTG). In POAG, NFP / SLP showed agreement with perimetric results in 35%/30% of cases and differences of one stage in 56%/58%. In NTG, NFP / SLP agreed with perimetry in 52%/48% of cases and differed by only one stage in 32%/39%. Larger deviations were found in less than 13% of the cases. Conclusions: NFP and SLP mostly showed good agreement or little deviation as to grading of nerve fiber layer damage. In clinical use, SLP has advantages over NFP because a higher rate of good-quality images can be obtained and pupils do not have to be dilated. Additionally, SLP measurements provide quantitative data and a large normative data base exists. Received: 15 February 2000 Revised: 13 June 2000 Accepted: 14 June 2000     

早期原发性开角型青光眼视盘血流密度的分析研究

目的:探讨早期原发性开角型青光眼(POAG)、高眼压症患者和健康者的视盘血流密度的差异。方法:横断面研究。收集2019-01/2021-04于福州东南眼科医院青光眼科门诊就诊患者,早期POAG组45例70眼,其中男32例49眼,女13例21眼,年龄48.50(26.75,64.50)岁,高眼压症组37例65眼,其中男17例29眼,女20例36眼,年龄37.00(27.00,47.00)岁,健康组51例94眼,其中男23例39眼,女28例55眼,年龄46.00(34.50,56.50)岁。分别对三组进行常规的眼科检查包括最佳矫正视力(BCVA)、眼压、视野、视网膜神经纤维层厚度(RNFL)、中央角膜厚度(CCT)等,通过光相干断层扫描血管成像检查(OCTA)采集并测量三组的视盘中心区、内层区、外层区和完整区的视盘血流密度。结果:三组眼压比较有差异(H=146.876,P<0.001),早期POAG组和高眼压症组与健康组的眼压值有差异(均P<0.01),早期POAG组和高眼压症组患者的眼压无差异(P=0.132)。早期POAG组和高眼压症组的BCVA、RNFL、MD值比较有差异(P=0.005、0.01、<0.01),早期POAG组和健康组两者的BCVA、RNFL、MD值比较有差异(P=0.013、<0.01、<0.01),高眼压症组和健康组两者的BCVA、RNFL、MD值比较无差异(P=1.000、0.660、1.000)。早期POAG组和健康组之间CCT无差异(P=0.074),早期POAG组和高眼压症组之间CCT比较有差异(P=0.006),高眼压症组和健康组之间CCT比较有差异(P<0.01)在中心区、内层区、完整区,早期POAG组和高眼压症组的血流密度比较有差异(均P<0.01),早期POAG组和健康组的血流密度比较有差异(均P<0.01),高眼压症组和健康组比较无差异(均P=1.000)。在外层区,早期POAG组和健康组的血流密度比较有差异(P=0.001),高眼压症组和早期POAG组及健康组比较有差异(P=0.067、0.877)。结论:早期POAG的视盘血流密度相比高眼压症和健康者是减少的,与视野MD、RNFL参数的变化是相一致的,早期POAG视盘不同区域血流密度均减少。     

Iris colour, optic disc dimensions, degree and progression of glaucomatous optic nerve damage

PURPOSE: To evaluate whether iris colour influences size and shape of the optic nerve head and risk for glaucoma progression. METHODS: The hospital-based observational study included 1973 eyes of 1012 Caucasian subjects with ocular hypertension or chronic open-angle glaucoma. For all patients, colour stereo optic disc photographs were evaluated, and corneal pachymetry and achromatic perimetry were performed. Main outcome measures were optic nerve head parameters, the development or progression of visual field defects and iris colour. RESULTS: In most of the study groups, size of the optic disc, neuroretinal rim, alpha zone and beta zone of parapapillary atrophy, retinal vessel diameter and central corneal thickness did not differ significantly between eyes with blue, green, brown and mixed iris colour. In the normal-pressure glaucoma group, neuroretinal rim area was smallest in the population with mixed-coloured eyes and largest in the group of eyes with brown irides (P = 0.001 after correction for inter-eye dependency and multiple testing). For the ocular hypertensive subjects and glaucoma patients with follow-up examinations, the rate of development or progression of glaucomatous visual field loss was not significantly associated with iris colour (P = 0.060). CONCLUSIONS: In Caucasian subjects, iris colour does not have a major association with the size of the optic nerve head structures, central corneal thickness and retinal arterial diameter. In Caucasian patients with ocular hypertension or chronic open-angle glaucoma, an influence of iris colour on the risk for development or progression of glaucomatous visual field defects could not be confirmed.     

Retinal blood flow measurements and neuroretinal rim damage in glaucoma

AIM: To assess retinal blood flow characteristics in subjects with normal tension glaucoma (NTG), primary open angle glaucoma (POAG), and a group of controls using the Heidelberg retina flowmeter (HRF). The vascular parameters were correlated against structural damage of the optic nerve head, assessed using the Heidelberg retina tomograph (HRT). METHODS: HRF images were obtained in 76 subjects with NTG, 58 with POAG, and 38 controls. Optic nerve head images, acquired using the HRT, were analysed with Moorfields Regression Analysis software. The HRF variables, measured adjacent to a rim segment identified as "abnormal," were compared with the vascular parameters of the "normal" rim segments. The HRF parameters of the segments identified as normal in glaucoma subjects were compared with matched control segments. RESULTS: The glaucoma subjects had significantly lower retinal haemodynamics than the control subjects. There were no significant differences in the HRF parameters between the NTG and POAG subjects. The discs that had been identified as having abnormal segments had lower HRF values than those with a corresponding normal segment. The glaucoma subjects with normal rim segments had statistically significant lower velocity, flow, and volume measurements than the controls for each location sampled. CONCLUSION: This study shows a relation between structural damage of the optic nerve head and the level of retinal blood flow. The changes in the circulation could indicate that it may be an early marker of the pathological process.     

POAG早期上下半视盘视网膜神经纤维层的不对称性变化

目的：：探讨原发性开角型青光眼( primary open angle glaucoma, POAG)早期上下半视盘周围视网膜神经纤维层( retinal nerve fiber layer, RNFL)的变化特征。方法：临床观察研究,研究对象为2012-05/2014-05在我院门诊确诊为原发性开角型青光眼早期患者30例39眼和健康成人20例40眼,使用Humphrey视野计和光学相干断层成像术( optical coherence tomography,OCT)检查,分别记录视野平均缺损( mean defect,MD)、青光眼半视野检测( glaucoma hemifield test, GHT)、眼压、C/D比值及视盘周围FNFL厚度。使用SPSS 18.0统计软件对测量值进行统计分析,计量资料组间比较采用t检验。结果：两组上半视盘各钟点位的RNFL厚度减去下半视盘相对应钟点位的RNFL厚度,两组间比较,仅上鼻-下鼻的差值具有统计学意义(t=2.526,P=0.014),其余上下半视盘相对应钟点位RNFL厚度的差值比较,两组间均无统计学意义(均为P>0.05)。结论：原发性开角型青光眼早期上下半视盘周围RNFL存在不对称性变化,上鼻部位(右眼1：00位,左眼11：00位)的RNFL较下鼻部位(右眼5：00位,左眼7：00位)的RNFL更容易受损变薄。     

Higher optic nerve sheath diameters are associated with lower ocular blood flow velocities in glaucoma patients

Purpose

To investigate the relationship between optic nerve sheath diameter (ONSD) and retrobulbar blood flow velocities, as measured by color Doppler imaging (CDI) in glaucoma patients.

Methods

We performed a prospective, randomized, observer-masked study involving a total of 197 subjects. Once enrolled, they were divided by three groups: healthy controls (n?=?51), normal-tension glaucoma patients (NTG, n?=?58), and primary, open-angle glaucoma patients (POAG, n?=?88). All subjects underwent a general ophthalmological examination, an ultrasound-based assessment of the ONSD, and a hemodynamic study of the retrobulbar vascularization using CDI. Non-parametric tests, chi-square contingency tables, and the Deming correlations were used to explore differences and correlations between variables in the diagnostic groups.

Results

ONSD was not different between experimental groups (p?=?0.28). ONSD correlated positively with the pulsatility index of the ophthalmic artery in healthy individuals (p?=?0.007), but not in glaucoma patients (NTG: p?=?0.41; POAG: p?=?0.22). In NTG patients, higher ONSD values were associated with lower end-diastolic and mean flow velocities in the short ciliary arteries (p?=?0.005 in both correlations). No such correlation was found in healthy nor POAG groups (p range between 0.15 to 0.96). ONSD was not associated with any CDI-related variable of the central retinal artery in any cohort. Venous outflow velocities were not associated with ONSD in any of the three groups.

Conclusions

ONSD is negatively correlated with retrobulbar blood flow velocities in glaucoma patients, but not in healthy controls.