Structural and functional assessment of the macular region in patients with glaucoma

PURPOSE: To investigate the correlation of a structural measure of the macular area (optical coherence tomography (OCT)) with two functional measures (10-2 Humphrey visual field (HVF) and multifocal visual evoked potential (mfVEP)) of macular function. METHODS: 55 eyes with open-angle glaucoma were enrolled. The 10-2 HVF was defined as abnormal if clusters of > or =3 points with p<5%, one of which had p<1%, were present. The mfVEP was abnormal if probability plots had > or =2 adjacent points with p<1%, or > or =3 adjacent points with p<5% and at least one of these points with p<1%. Two criteria were used for the macular OCT: (I) > or =2 sectors with p<5% or 1 sector with p<1% and (II) 1 sector with p<5%. RESULTS: 54 of the 55 eyes showed an abnormal 10-2 HVF and 50 had central mfVEP defects. The two OCT criteria resulted in sensitivities of 85% and 91%. When both functional tests showed a defect (in 49 eyes), the OCT was abnormal in 45. For the OCT the outer and inner inferior regions were the most likely to be abnormal, and both functional techniques were most abnormal in the superior hemifield. CONCLUSIONS: Good agreement exists between macular thickness and functional defects in patients with glaucoma. Study of the macular region may provide a quantitative measure for disease staging and monitoring.     

Threshold testing of the macular area in glaucoma

The purpose of this study has been to verify whether threshold testing of the central area with a common automated perimeter could detect glaucomatous damage. We selected 31 eyes of 31 patients with primary open angle glaucoma free from defects within the central 5 degrees of the field and 32 eyes of 32 age-matched normal subjects. They underwent the Macula Threshold Test of the Humphrey Field Analyzer using white and blue targets. Statistical analysis of the results obtained showed that threshold sensitivities to both white and blue targets were significantly depressed in glaucomatous eyes (t = 2.44, p = 0.018 and t = 12.59, p less than 0.001 respectively), but only blue thresholds distributed really differently in glaucomatous and normals. Sensitivities to blue stimuli related to age only in normals (r = 0.58; p = 0.0005), while in glaucomatous they were related to cup/disc ratios (r = 0.70, p less than 0.0001 for horizontal C/D; r = 0.52, p = 0.0027 for vertical C/D). These results suggest that it is possible to detect early central functional disturbances from glaucoma using an automated perimeter and its built-in color filters.     

正视视野前期青光眼的存在

原发性开角型青光眼(POAG)为慢性进行性视神经病变, 其特征为疾病早期无症状, 进入中晚期病情难以控制, 可导致不可逆盲, 因此早期诊疗极为重要。视野缺损是其重要的诊断标准。近年来临床针对POAG提出视野前期青光眼(PPG)概念, 即临床标准全自动视野计检查结果正常, 但已存在明确的青光眼视神经结构改变, 病情进展可导致视野缺损, 由视野无缺损阶段(临床极早期青光眼)进入功能损伤阶段(临床早、中、晚期青光眼)。本文通过阐述和分析PPG的定义、发生机制、临床证据以及诊断方法、治疗价值等, 提出临床正视PPG的存在, 有助于及时发现POAG病情, 重视随访并准确判断和把握治疗时机, 这是预防POAG视野缺损的关键。     

Structural and functional assessment after intravitreal injection of ranibizumab in diabetic macular edema

Purpose

To evaluate structure and function improvement in central retina by optical coherence tomography (OCT) and multifocal electroretinography (mf-ERG) in diabetic macular edema (DME) patients after intravitreal injection of ranibizumab (IVR) treatment.

Methods

Twenty-seven eyes in 27 patients with DME received three consecutive monthly injections of IVR (0.05 ml, 10 mg/ml) and as needed thereafter. The clinical parameters of best-corrected visual acuity (BCVA), central foveal thickness (CFT) and mf-ERG were monitored for 6 months before and after IVR. The findings at baseline, 1, 3 and 6 months were analyzed. Correlation and regression analyses were performed on BCVA, CFT, mf-ERG amplitude and implicit time of the N1 and P1 waves.

Results

IVR significantly improved visual acuity from the beginning of the treatment (P < 0.05). There were significant decreases in the CFT compared with the baseline after IVR (P < 0.05). The mean amplitude of P1 and N1 in the central ring at all examinations increased significantly compared with the baseline (P < 0.05). The mean P1 and N1 implicit times in the central ring were shortened, but not significantly (P > 0.05). There were significant correlations of BCVA with CFT, P1 and N1 amplitudes in the central retina (P < 0.05).

Conclusion

In addition to the improvement in BCVA and the reduction in CFT, IVR improved macular retinal function, as assessed by mf-ERG, in diabetic eyes. The combination of OCT and mf-ERG for macular evaluation may better assess DME.

     

黄斑内层视网膜厚度测量在青光眼早期诊断和随访中的应用

青光眼是一组以视盘凹陷性萎缩和视野进行性损害为特点的不可逆性致盲眼病。传统视野“金标准”及视网膜全层厚度测量在青光眼诊断中具有一定的滞后性和局限性,而黄斑区内层厚度测量由于其生理优势可能有助于早期青光眼诊断。目前快速发展的OCT技术已经能够分离测量视网膜黄斑内层厚度,至今也已有多篇文献报道黄斑内层厚度测量在早期青光眼中具有较好的诊断效能且发现其基线指标可能对青光眼进展有预测价值。     

Comparative study of macular ganglion cell complex thickness measured by spectral-domain optical coherence tomography in healthy eyes,eyes with preperimetric glaucoma,and eyes with early glaucoma

Purpose

To evaluate the diagnostic accuracy of Topcon 3D spectral-domain optical coherence tomography (SD-OCT) for measuring the macular inner retinal layers and the circumpapillary retinal nerve fiber layer (cpRNFL) in order to detect preperimetric glaucoma.

Methods

Two hundred four eyes, including 64 healthy eyes, 68 eyes with preperimetric glaucoma, and 72 eyes with early glaucoma were analyzed. Patients had a comprehensive ocular examination including visual field testing and SD-OCT imaging (3D OCT-2000; Topcon Corporation, Tokyo, Japan) in the macular and peripapillary regions. OCT macular scans were segmented into the macular nerve fiber layer (mNFL), ganglion cell layer with the inner plexiform layer (GCIP), and ganglion cell complex (GCC) (composed of the mNFL and GCIP). Ability to discriminate preperimetric glaucoma was assessed using the area under the receiver operating curve for all macular parameters and the cpRNFL.

Results

The median visual field MD was ?0.78 ± 1.19 dB for the healthy group, ?1.02 ± 1.29 dB for the preperimetric glaucoma group, and ?3.08 ± 1.61 dB for the early glaucoma group. There were significant differences between the preperimetric and healthy groups for GCIP and GCC and for almost all cpRNFL thickness parameters (P < 0.05), except for the mNFL and cpRNFL (nasal, 3, 4, 8, 9, and 10 o’clock sectors). The comparisons among the AUCs of the cpRNFL parameters (0.772), the GCIP parameters (0.727) and the GCC parameters (0.720) showed no significant differences in their abilities to detect preperimetric glaucoma.

Conclusions

The capacity of Topcon 3D-OCT macular intraretinal parameters (GCIP and GCC measurements, not mNFL measurements) to diagnose preperimetric glaucoma is similar to that of the cpRNFL.     

Blue-on-yellow perimetry and optical coherence tomography in patients with preperimetric glaucoma

Purpose: To investigate the diagnostic ability of blue‐on‐yellow perimetry (B/YP) and Stratus optical coherence tomography (OCT) in discriminating preperimetric glaucoma from normal eyes. Methods: A total 40 eyes of 40 normal subjects, 38 eyes of 38 preperimetric glaucoma patients (normal standard automated perimetry [SAP] and retinal nerve fibre layer [RNFL] defects or localized optic disc notching and thinning) were enrolled in the study. All the patients underwent SAP and B/YP tests, and OCT measurements. The correlation between B/YP indices and OCT parameters in the eyes with preperimetric glaucoma was analysed. Receiver operating characteristic (ROC) curve area was calculated to discriminate preperimetric glaucoma from normal eyes. Results: In preperimetric glaucoma, 42% eyes (16/38) had B/YP visual field loss, and 68% eyes (26/38) had RNFL defects with OCT measurements. A mild significant correlation was found between B/YP pattern standard deviation (PSD) and average RNFL thickness (Avg.Thi) (R² = 0.112, P = 0.012), superior maximum (Smax) (R² = 0.140, P = 0.005) and maximum‐minimum (Max‐Min) (R² = 0.074, P = 0.042) in the preperimetric glaucoma group. The areas under the ROC curve for B/YP PSD and B/YP mean deviation were 0.721 and 0.665, respectively, and the three OCT parameters with the widest areas under the ROC curve were Avg.Thi (0.719), inferior average (Iavg) (0.718) and nasal average (Navg) (0.706). The highest sensitivity of the individual B/YP indices and OCT parameters for detection of preperimetric glaucoma was B/YP mean deviation (32%) and Smax/Navg (40%) at 90% specificity; the highest sensitivity of the individual B/YP indices and OCT parameters was B/YP PSD (49%) and Iavg (56%) at 80% specificity. Conclusion: The sensitivity of B/YP indices and Stratus OCT RNFL thickness parameters is low for detecting preperimetric glaucoma, suggesting that BYP and OCT as utilized in this study have limited utility in the detection of preperimetric glaucoma.     

Development of visual field defect after first-detected optic disc hemorrhage in preperimetric open-angle glaucoma

Purpose

To evaluate functional progression in preperimetric glaucoma (PPG) with disc hemorrhage (DH) and to determine the time interval between the first-detected DH and development of glaucomatous visual field (VF) defect.

Methods

A total of 87 patients who had been first diagnosed with PPG were enrolled. The medical records of PPG patients without DH (Group 1) and with DH (Group 2) were reviewed. When glaucomatous VF defect appeared, the time interval from the diagnosis of PPG to the development of VF defect was calculated and compared between the two groups. In group 2, the time intervals from the first-detected DH to VF defect of the single- and recurrent-DH were compared.

Results

Of the enrolled patients, 45 had DH in the preperimetric stage. The median time interval from the diagnosis of PPG to the development of VF defect was 73.3 months in Group 1, versus 45.4 months in Group 2 (P = 0.042). The cumulative probability of development of VF defect after diagnosis of PPG was significantly greater in Group 2 than in Group 1. The median time interval from first-detected DH to the development of VF defect was 37.8 months. The median time interval from DH to VF defect and cumulative probability of VF defect after DH did not show a statistical difference between single and recurrent-DH patients.

Conclusions

The median time interval between the diagnosis of PPG and the development of VF defect was significantly shorter in PPG with DH. The VF defect appeared 37.8 months after the first-detected DH in PPG.

     

Interpretation of the Humphrey Matrix 24-2 test in the diagnosis of preperimetric glaucoma

Purpose  To define the diagnostic precision of the Humphrey Matrix 24-2 test and to determine a clinically applicable cutoff criterion for the inclusion of preperimetric glaucoma. Methods  Eyes with preperimetric glaucoma (99 eyes) were defined as having normal standard automated perimetry (SAP) results and a glaucomatous optic nerve head, along with one or more optical coherence tomography (OCT) parameters flagged as <0.05 or a retinal nerve fiber layer (RNFL) defect on red-free fundus photographs. Normal controls (122 eyes) were defined as having a normal optic disc and RNFL with normal SAP. Receiver—operating characteristic (ROC) curves were constructed to determine the best-discriminating parameter of the frequency-doubling technology (FDT) Matrix. The sensitivity, specificity, and hit ratio of all available criteria were calculated from the FDT Matrix. Results  Pattern standard deviation (PSD) showed a larger area under the ROC curve (AUC) (0.767) than mean deviation (MD) (0.619). A pattern deviation plot (PDP) analysis by modified Anderson criteria showed the highest discriminating power, with a sensitivity of 75.76%, followed by a PSD cutoff value of 3.14 dB (sensitivity, 73.74%). Conclusions  FDT Matrix seems to be a valuable clinical tool in the detection of preperimetric glaucoma. Among the parameters of the FDT Matrix, PDP analysis by modified Anderson criteria may provide a reliable cutoff criterion.     

Macular integrity assessment to determine the association between macular microstructure and functional parameters in diabetic macular edema

AIM: To respectively evaluate macular morphological features and functional parameters by using spectral-domain optical coherence tomography (SD-OCT) and macular integrity assessment (MAIA) in patients with diabetic macular edema (DME). METHODS: This prospective, non-controlled, open study included 61 eyes of 38 consecutive patients with DME. All patients underwent best-corrected visual acuity (BCVA) measurement, MAIA microperimetry, and SD-OCT. DME morphology, including central retinal thickness (CRT) and central retinal volume (CRV); integrity of the external limiting membrane (ELM) and photoreceptor inner segment/outer segment (IS/OS) junction; and the deposition of hard macular exudates were assessed within a 1000-μm central subfield area. MAIA microperimetry parameters evaluated were average threshold (AT)-retinal sensitivity, macular integrity index (MI), fixation points within a circle of radius 1° (P1) and 2° (P2), and bivariate contour ellipse area considering 63% and 95% of the fixation points (A63 and A95, respectively). RESULTS: MI was significantly higher in eyes with disrupted ELM or IS/OS, compared with eyes with intact ELM and IS/OS. Values of BCVA (logMAR), total AT, AT within 1000-μm diameter, P2, A63, A95, and CRT were significantly worse in eyes with disrupted IS/OS, compared with eyes with intact IS/OS. The values of BCVA (logMAR), AT within 1000-μm diameter, and CRT were significantly worse in eyes with disrupted ELM, compared with eyes with intact ELM. These parameters were not significantly different between eyes with or without hard macular exudate deposition. CRV was not significantly different in the presence or absence of the integrity of ELM, IS/OS, or deposition of hard macular exudates. At the center, nasal and temporal sectors of the fovea, significant negative correlations were observed between retinal thickness and AT of the corresponding area. At the inferior and superior sectors of the fovea, no correlations were observed between retinal thickness and AT of the corresponding area. In the intact IS/OS group, significant negative correlations were observed between CRT and central AT. There was no correlation between retinal sensitivity and thickness when the IS/OS layer was disrupted. Multiple linear regression analyses revealed that IS/OS integrity was an independent factor affecting MI. CONCLUSION: Functional (BCVA and visual field) and morphological parameters (retinal thickness) were significantly associated with an intact IS/OS. Local photoreceptor integrity was a strong predictor of local visual function throughout the retina. MI revealed the functional status in DME, reflecting the IS/OS juction status in the macula.     

Frequency-doubling technology and retinal measurements with spectral-domain optical coherence tomography in preperimetric glaucoma

Background

To determine the relationship between visual fields and retinal structures measured with spectral-domain optical coherence tomography in preperimetric glaucoma (PPG).

Methods

Twenty-six eyes of 26 patients with PPG and 20 healthy eyes of 20 volunteers were included. All patients underwent Heidelberg retina tomography-2 (HRT2), standard automated perimetry (SAP), frequency-doubling technology (FDT) perimetry, and RTVue-100. SAP and FDT indices, HRT parameters, and circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) thicknesses were correlated using Pearson’s test. Areas under the receiver operating characteristic curves (AUROCs) and sensitivity/specificity based on each parameter’s definition of abnormalities were compared between parameters.

Results

Significant differences were found in FDT-MD, FDT-PSD, SAP-PSD, cpRNFL, and mGCC parameters (p?<?0.001–0.015), but not in SAP-MD or HRT parameters, between PPG and control groups. Significant correlations were not found between visual field indices and structural parameters, except between FDT-MD and HRT rim area (r?=?0.450, p?=?0.021) and between FDT-PSD and temporal cpRNFL thickness (r?=?0.402, p?=?0.021). AUROCs for cpRNFL (p?=?0.0047–0.033) and mGCC (p?=?0.0082–0.049) parameters were significantly better than those of HRT parameters, whereas significant differences were not found between FDT indices and cpRNFL or mGCC parameters or between cpRNFL and mGCC parameters. Adding average cpRNFL or mGCC thickness to FDT-MD significantly increased sensitivity compared to single parameters (p?=?0.016–0.031).

Conclusions

Structural and functional parameters were poorly correlated but complementary for glaucoma detection in PPG. Combining these parameters may improve PPG diagnosis.     

The development of hemispheric asymmetry in human motion VEPs

In six healthy adults we examined the sources underlying P1 and N2 of the motion VEP. For this purpose was acquired, in addition to the VEP, MRI images and patterns of regional cerebral blood flow with SPECT for three of the subjects. With the same motion stimulus we also examined the spatial distribution of N2 in children. In both adults and children left and right half-field responses were compared. It was found that N2 is generated by extrastriate activity and that motion stimuli are not equivalently processed in the two cerebral hemispheres. In adults, N2 dominates in one hemisphere irrespective of the visual half-field used for stimulation whereas children show an ipsilateral maximum for N2 upon half-field presentation.     

Optic nerve head parameters of high-definition optical coherence tomography and Heidelberg retina tomogram in perimetric and preperimetric glaucoma

Background:Heidelberg retina tomogram (HRT) and optical coherence tomography (OCT) are two widely used imaging modalities to evaluate the optic nerve head (ONH) in glaucoma.Purpose:To compare the ONH parameters of HRT3 and high-definition OCT (HD-OCT) and evaluate their diagnostic abilities in perimetric and preperimetric glaucoma.Design:Cross-sectional analysis.Methods:35 control eyes (24 subjects), 21 preperimetric glaucoma eyes (15 patients), and 64 perimetric glaucoma eyes (44 patients) from the Longitudinal Glaucoma Evaluation Study underwent HRT3 and HD-OCT examinations.Results:Optic disc area, vertical cup to disc ratio, and cup volume with HD-OCT were larger than with HRT, while the rim area was smaller with HD-OCT (P < 0.001 for all comparisons). AUCs of all HD-OCT ONH parameters (0.90-0.97 in perimetric and 0.62-0.71 in preperimetric glaucoma) were comparable (P > 0.10) to the corresponding HRT ONH parameters (0.81-0.95 in perimetric and 0.55-0.72 in preperimetric glaucoma). LRs associated with diagnostic categorization of ONH parameters of both HD-OCT and HRT were associated with larger effects on posttest probability of perimetric compared to preperimetric glaucoma.Conclusions:ONH measurements of HD-OCT and HRT3 cannot be used interchangeably. Though the diagnostic abilities of ONH parameters of HD-OCT and HRT in glaucoma were comparable, the same were significantly lower in preperimetric compared to perimetric glaucoma.     

Diagnostic evaluation of optical coherence tomography parameters in normal, preperimetric and perimetric glaucoma patients

AIM: To compare the diagnostic ability of glaucoma parameters measured by the optical coherence tomography (OCT) in normal, preperimetric glaucoma (PPG) and perimetric glaucoma (PG) patients.METHODS: This cross-sectional observational study includes 127 eyes of 127 subjects. Patients were divided into PPG (51 eyes), PG (46 eyes), and normal controls (30 eyes) based on clinical optic disc assessment and Humphrey visual field changes. The Heidelberg Spectralis OCT machine using Glaucoma Module Premium Edition software was used to measure the retinal nerve fiber layer (RNFL) and Bruch’s membrane opening-minimum rim width (BMO-MRW) to assess the optic nerve head and ganglion cell layer (GCL) thickness in the macula.RESULTS: RNFL, MRW, and GCL thickness were all significantly thinner in PG compared to PPG and the normal group. The BMO-MRW parameters showed better specificity (>70%) at 90% specificity compared to both RNFL and GCL parameters to discriminate normal, PPG, and PG patients. All BMO-MRW parameters showed higher area under curves (AUC) compared to RNFL and GCL parameters with the highest AUC observed in the superotemporal sector of the BMO-MRW (AUC=0.819 and and 0.897 between normal and PPG and PG groups respectively).CONCLUSION: While the BMO-MRW best discriminates PPG and PG against normal eyes, GCL parameters poorly differentiate the three groups.