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Quantitative detection of glaucomatous damage at the posterior pole by Retinal Thickness Mapping
Abstract
The posterior pole ganglion cell bodies form a substantial fraction of the retinal thickness, prompting the authors to study the feasibility of detecting, by scanning retinal thickness analysis, retinal changes at the posterior pole due to glaucomatous damage.
Nonconsecutive case series.
One or both eyes of patients with chronic open-angle glaucoma who presented with either a superoinferior asymmetry in visual fields or a localized field loss or a nerve fiber layer defect visible on photography were recruited. Twenty-nine eyes of 18 patients were studied.
A laser slit was projected on the retina and scanned, in 400 msec, across a 2- x 2-mm area of the fundus, yielding optical cross-sections that were digitally recorded. Nine such scans covered the central 20 degrees of the fundus. The optical cross-sections were analyzed by an operator-free algorithm to yield a three-or two-dimensional color map. The asymmetry (difference) between the visual sensitivity of the upper and lower hemifields was compared with the asymmetry in retinal thickness deviation from normal.
Large losses (up to 34%) in retinal thickness were detected at the posterior pole of patients with glaucoma due to the loss of ganglion cells and nerve fibers. A statistically significant correlation was found between the asymmetry in visual sensitivity loss and the asymmetry in deviation from normal thickness (r = 0.72; P < 0.0005).
Mapping of the retinal thickness may provide a sensitive method for the detection and monitoring of early glaucomatous tissue loss in the posterior pole, which is unique due to the combination of (1) the direct measurement of neuroretinal loss in the central field of vision; (2) the mapping capability; and (3) the rapid image acquisition.
... Macula, the only place in retina where RGC bodies are stacked up to six layers thick, constitutes more than 50% of the RGCs of the entire retina. Since the RNFL comprises of the RGC axons; therefore, assessment of the RGCs may be a more direct method of evaluation of glaucomatous damage than peripapillary RNFL (ppRNFL) thickness, also the cell body is substantially larger than the axons of the RGCs which makes more part of the thickness than the axon does and thus might improve the ability to detect damage to these cells [10,17,18]. Allowing scanning and accurate quantitative assessment of the macula, optical coherence tomography aids sampling of the majority of the RGCs. ...
... MT evaluation received gross attention after Zeimer et al. [17] hypothesized that quantitative detection of glaucomatous damage at macula may provide a method for detection and monitoring of early glaucomatous damage. Although some studies favor MT as a valuable surrogate measure for evaluating glaucomatous structural changes, the presence of contrasting reports on its discriminating power and reproducibility is ordinary. ...
... Our study is in accordance with the Zeimer et al. [17] hypothesis of decreasing macular volume with advancing disease. Giovannini et al. [20], Parikh et al. [21], Sharma et al. [22], Khanal et al. [23], and Lederer et al. [24] found results consistent to ours among POAG and control groups whereas Lederer et al. [24] in the same study did not find variation significant enough among POAG suspects and controls where though the inclusion criteria and methods were similar, the calculation of macular volume was performed manually after estimation of MT from commercially available OCT1 machine. ...
Introduction: Primary open-angle glaucoma is a silent predator of sight, killing retinal ganglion cells (RGCs), and leads to characteristic optic nerve head (ONH) changes and visual field (VF) defects. The conventional methods of diagnosis include clinical examination and perimetry. However, by these at the time of diagnosis, a substantial loss of RGCs has already occurred. Spectral domain optical coherence tomography (SD-OCT) allows quantitative measurements of various parameters of the retina. This tool may be utilized for selective measurement of macular parameters to make an early diagnosis of primary open angle glaucoma (POAG). Methods: In 6 months of study, a total of 81 eyes of 51 subjects underwent SD-OCT measurements, that is, 49 eyes of 35 POAG subjects and 32 eyes of 16 age-matched healthy subjects, to record all measurable macular parameters, namely, macular thickness (MT)-central, average, in all sectors of the inner and outer circle of early treatment of diabetic retinopathy study (ETDRS) macular map; macular volume, ganglion cell-inner plexiform layer (GC-IPL) thickness-in all sectors; succeeded by statistical calculations using the unpaired t-test to calculate two-tailed p-value which is significant when its value is <0.05. Results: As an observation the average MT, MT in the inferior and temporal sector of the inner circle of the ETDRS macular map, that in the inferior sector of the outer circle, minimum GC-IPL thickness, and GC-IPL thickness in all sectors were all significantly reduced in POAG eyes than healthy eyes. Whereas central MT, average GC-IPL thickness, macular volume, and MT in few sectors of the inner and outer circle of the ETDRS macular map proved to bear an insignificant change of POAG. Conclusion: In this study, the greatest impact of POAG on macula was discovered in the GC-IPL layer and MT in the inferior sector of inner and outer ring which might serve the purpose of diagnosis of POAG apart from the established parameters of RNFL and ONH.
... The superficial layer mVD depicts the VD of the SVP, which supplies the RNFL and RGCs, while the deep layer mVD relates to the perfusion of the DVP supplying the horizontal cells in the outer nuclear layer 23 . Considering that the RNFL and RGCs are the primary sites for glaucomatous structural damage 24 , glaucomatous change may be more closely related to changes in the Table 3. Univariable and multivariable Cox regression analyses to identify clinical factors associated with visual field progression. Values with statistical significance are presented in bold. ...
... Our current study findings are in line with previous results that revealed a significant correlation between superficial layer mVD reduction and glaucomatous damage 7,8,25 . Hou et al. 24 reported that the superficial layer mVD decreased more rapidly in primary open-angle glaucoma eyes compared to preperimetric glaucoma or healthy eyes. This implies that a faster decrease in the superficial layer mVD is associated with more severe glaucomatous damage. ...
Identifying the clinical relevance of superficial versus deep layer macular vessel density (mVD) in glaucoma is important for monitoring glaucoma patients. Our current retrospective longitudinal study investigated the association of superficial and deep layer mVD parameters with glaucomatous visual field (VF) progression in mild to moderate open-angle glaucoma (OAG) eyes with central visual field (CVF) damage. Serial optical coherence tomography (OCT) angiography-derived mVD measurements were obtained in 182 mild to moderate OAG eyes (mean deviation ≥ -10 decibels). Forty-eight eyes (26.4%) showed VF progression during a mean follow-up of 3.5 years. The parafoveal and perifoveal mVDs of both superficial and deep layers showed significantly faster reduction rates in the VF progressors than in the non-progressors according to linear mixed effects models (P < 0.05). Cox and linear regression analyses showed that greater reduction rates of both the superficial layer parafoveal and perifoveal mVDs, but not their deep layer counterparts, were significant predictors of VF progression and faster VF loss (P < 0.05). In conclusion, faster rates of change in superficial but not deep layer mVD parameters are significantly associated with subsequent VF progression and faster VF deterioration in mild to moderate OAG eyes with CVF damage.
... 21 The correlation between reduced ssPERG parameters and reduced total macular thickness found in this study is also in line with previous studies that have found reduced macular thickness in patients with glaucoma. 38,39 It has been suggested that this is secondary to the thinning in the GCL/IPL layers. 39 The macular region has been reported to contain approximately 50% of all RGCs, which are reduced in glaucoma, and there is a strong association between macular RGC density and GCL/IPL thickness. ...
... 38,39 It has been suggested that this is secondary to the thinning in the GCL/IPL layers. 39 The macular region has been reported to contain approximately 50% of all RGCs, which are reduced in glaucoma, and there is a strong association between macular RGC density and GCL/IPL thickness. 40,41 Interestingly, ssPERG had significant correlations with all the inner sector thicknesses and had a much weaker correlation with the outer sector thicknesses of the macula in this study. ...
Aim:
To investigate whether steady state pattern electroretinogram (ssPERG) could identify retinal ganglion cell (RGC) dysfunction, and to assess the relationship between ssPERG with optical coherence tomography (OCT) measurements in glaucoma suspects (GS).
Materials and methods:
This was a prospective cohort study of GS, identified based on suspicious optic disk appearance and glaucoma risk factors. Complete eye exam, Standard automated perimetry, OCT, and ssPERG were performed. Magnitude (Mag), Magnitude D (MagD), and MagD/Mag ratio were subsequently used in the correlation and linear regression analyses between ssPERG parameters and the RNFL, GCL/IPL, and macular thicknesses measurements.
Results:
Forty-nine eyes of 26 patients were included. Mag and MagD were significantly correlated with the superior, inferior, and average RNFL thicknesses (avRNFLT). All ssPERG parameters were significantly correlated with the average and minimum GCL/IPL thicknesses and the inner macular sector thicknesses. Mag and MagD significantly predicted the superior, inferior, and avRNFLT in the regression analysis. All ssPERG parameters were predictive of GCL/IPL thickness in all sectors as well as the average and minimum GCL/IPL thicknesses. All ssPERG parameters were predictive of all inner macular sector thicknesses and MagD was also predictive of some outer macular sector thicknesses as well.
Conclusion:
ssPERG has significant correlations with and is predictive of RNFL, GCL/IPL, and macular thicknesses in glaucoma suspects.
Clinical significance:
ssPERG may serve as a useful objective functional tool for identifying and following the progression of disease in glaucoma suspects.
How to cite this article:
Tirsi A, Wong A, Zhu D, et al. Pattern Electroretinogram Parameters and their Associations with Optical Coherence Tomography in Glaucoma Suspects. J Curr Glaucoma Pract 2022;16(2):96-104.
... Zeimer y otros plantearon la hipótesis de que la pérdida de CGR en el glaucoma temprano es más probable que ocurra en esta estructura. (11) Identificar un método preciso para medir esta pérdida permitiría la detección temprana del glaucoma y el monitoreo de su progresión. ...
... Solo en el glaucoma, el cambio del grosor macular es típicamente arciforme; no adquiere esta disposición cuando se afecta por otras enfermedades. (11) En el caso del sistema CIRRUS, recomendamos identificar en el patrón de células ganglionares formas típicas, denominadas "en caparazón de caracol". Son formas típicas de los defectos que vemos en la zona inferior. ...
Glaucoma is an optic neuropathy characterized by the loss of retinal ganglion cells and their axons. It is the leading cause of irreversible blindness worldwide, hence the crucial importance of its timely detection and continuous monitoring. Optical coherence tomography measurement of circumpapillary retinal nerve fiber layer thickness is the main structural evaluation strategy to diagnose glaucoma. However, in view that the macula is the retinal area related to central vision and contains 50% of the retinal ganglion cells, measuring macular thickness seems to be a good option for early detection of the death of these cells. The present review discusses the antecedents, anatomical justification, protocols and main artifacts of macular optical coherence tomography as related to the care of glaucoma. An updated approach is also provided to the way these explorations may be used in clinical practice.
... However, there is significant evidence of structural and functional losses in areas of high acuity, even at early stages of disease. [1][2][3][4][5][6][7][8][9][10] In fact, it has been shown that macular tests of visual function using 10-2 perimetry, in addition to macula optical coherence tomography (OCT) imaging, can be beneficial for glaucoma management. 11 The macula region has the highest density of RGCs, and in vivo OCT can be used to reliably quantify the inner retinal thickness. ...
... Furthermore, axon counts using this method have been compared to circumpapillary RNFL thickness for 15 eyes with experimental glaucoma (including the four animals used for histologic work in the current study) and 12 normal control eyes (Antwi-Boasiako K, et al. IOVS 2017;58 (8):4025). Axon counts using the methods described are linearly related to the circumpapillary RNFL thickness (Fig. 1) and similar to that previously reported. 35 . ...
Purpose:
Loss of ganglion cell inner plexiform layer (GCIPL) and visual sensitivity in the macula region are known to occur at all stages of glaucoma. While both are dependent on the underlying retinal ganglion cells (RGCs), the relationship between structure and function is modest. We hypothesize that the imprecise relationship is due to a lack of direct correspondence between in vivo measures and RGC counts, as well as the relatively large stimulus size used by standard perimetry, which exceeds spatial summation.
Methods:
The relationship between optical coherence tomography (OCT)-derived GCIPL thickness and corresponding inner cell density from retinal flat mounts was determined for four nonhuman primates with varying stages of neuropathy. Normative data for 10-2 threshold using Goldman size I to V stimuli were established for 10 animals, 4 of which were then followed longitudinally with OCT and perimetry. The relationship between GCIPL volume, which incorporated stimulus size after removal of residual thickness, and differential light sensitivity was determined for both experimental glaucoma and healthy eyes.
Results:
Peak inner retinal cell density was 63,052 ± 9238 cells/mm2 in the healthy eye. Cell density was related to both GCIPL thickness and eccentricity (R2 = 0.74, P < .01). For all 10-2 eccentricities, size III stimuli were greater than the critical area (P < 0.01). Based on the structural and histologic relationship, the critical area corresponds to approximately 156 RGCs.
Conclusions:
The relationship between cell density and GCIPL thickness is dependent on retinal eccentricity. For 10-2 perimetry, perimetric loss, especially at earlier stages of neuropathy, may best be detected using size II or smaller stimuli.
... Thus, as the FLV and GLV values increased, visual field sensitivity decreased (Table 3) which is similar to a study in India [21]. This concurrent relationship between RNFL and GCC parameters and visual field sensitivity has been suggested to be useful in the accurate diagnosis of glaucoma in suspected cases [26,27]. The strong association observed between the retinal structure and function in the average POAG group was not evident in the early stages of the disease (Table 3) which is consistent with the findings of Chu et al. [28], who found no significant association between the structure and function in non-glaucomatous eyes and the early stages of glaucoma. ...
... The findings of this study provide a good basis to reemphasize the fact that because structural changes precede perimetric visual field changes, sensitive imaging tools can improve the practitioners' ability to detect early glaucoma and allow timely intervention to prevent vision loss [27,36]. ...
Purpose
The objective of this study was to determine the structure–function association of the optical coherence tomography (OCT) indices (retinal nerve fibre layer (RNFL), ganglion cell complex (GCC) and optic nerve head (ONH) parameters) with the visual field sensitivity and their diagnostic ability at different stages of primary open-angle glaucoma (POAG) among a population West-African descent.
Methods
The study was a clinic-based prospective study which employed purposive-sampling in the recruitment of clinically diagnosed POAG and non-glaucoma patients. OCT and visual field test (VFT) results were collated. Classification of the POAG cases was done using the Hodapp–Parrish–Anderson criteria. ROC was used for assessing the diagnostic ability of OCT indices. Pearson’s correlation was used to assess the structure–function association. P value < 0.05 was considered statistically significant.
Conclusions
Of the 497 subjects (497 eyes), 301 (60.6%) were males and 196 (39.4%) were females. The average, superior and inferior RNFL and GCC showed a strong positive correlation with the visual field sensitivity, but the average RNFL had the highest correlation (r = 0.673, p < 0.001). The parameters of the ONH showed a moderate-to-weak correlation with the visual field sensitivity. However, there was no significant correlation between structure and function in early POAG (p > 0.05). Superior GCC showed the highest diagnostic ability for POAG (AUC = 0.655; p < 0.001) comparable to the RNFL. Macula (GCC) and (RNFL) have a comparable ability to diagnose POAG at all the stages of POAG and can be used complimentarily for glaucoma assessment and diagnosis.
Keywords: Primary open-angle glaucoma (POAG). Retinal nerve fibre layer (RNFL). Ganglion cell complex (GCC). Optic nerve head (ONH)
Full PDF: https://rdcu.be/caLWN
... superior, outer inferior, outer nasal, and outer temporal) and macular volume measurements showed significant macular volume at( fovea, inner superior, inner inferior, inner nasal, inner temporal, outer superior, outer inferior, outer nasal and outer temporal) in control group than glaucoma group 13 . to be further investigated 6 . ...
EJO(MOC) 2024;4(1):40-50. Short title: Macular Thickness and Volume Analysis in POAG By OCT Abstract Purpose: the aim of the current study was to compare the difference of retinal macular thickness and macular volume using optical coherence tomography (OCT) between normal subjects and POAG patients. Methods: This was a case-control observational study held in Mansoura university ophthalmic center during the period from April 2021 to June 2022 on a sample size of 100 eyes. Eyes were divided into 2 groups; group A which include glaucoma group (50 eyes) and Control group (group B) of normal subjects (50eyes). Eyes underwent O.C.T macula (macular volume and macular thickness) by using SS-OCT (3D DRI OCT Triton [plus], Topcon Corporation, Tokyo, Japan). Results: Macular thicknesses and macular volume had significant decreased in all macular quadrants (fovea), Inner (Superior, inferior nasal, temporal) and Outer (Superior, inferior, nasal, temporal) quadrants in the glaucoma patients compared to the controls. RNFL thicknesses had significant decreased in Inferior, superior, nasal, temporal quadrants in the glaucoma patients compared to the controls. Conclusion: This data showed a significant difference in macular volume and macular thickness between normal, compared to glaucomatous eyes in all macular quadrants including fovea, Inner (Superior, inferior, nasal, temporal) and Outer (Superior, inferior, nasal, temporal) so they could be used as reliable indicators to differentiate between cases and the normal subjects.
... 39 Leading up to the introduction of PPAA, several studies reported that the evaluation of macular thickness could be an effective method to evaluate for glaucomatous damage. [40][41][42] The pathophysiologic basis of the PPAA protocol is that in open-angle glaucoma, because of increased intraocular pressure, early glaucomatous damage is typically localized to either the superior or inferior side of the horizontal meridian, and rarely both simultaneously. In normal tension glaucoma, this asymmetry in hemifields is not seen; instead, centralized defects around the central macular region are observed. ...
Purpose
Spectral domain optical coherence tomography (SD-OCT) with posterior pole asymmetry analysis (PPAA) provides a mapping of posterior pole retinal thickness with asymmetry analysis between hemispheres of each eye. We investigated whether these structural abnormalities were correlated with functional retinal ganglion cell (RGC) loss, quantified by steady state pattern electroretinogram (ssPERG), in glaucoma suspects (GS).
Methods
Twenty GS (34 eyes) were enrolled in a prospective study at the Manhattan Eye, Ear, and Throat Hospital. All subjects underwent ophthalmological examination, including Humphrey visual field, Spectralis Glaucoma Module Premium Edition (GMPE) SD-OCT PPAA, and ssPERG testing. The ability of ssPERG parameters (Magnitude [Mag, µv], MagnitudeD [MagD, µv], and MagD/Mag ratio) to predict PPAA thickness (total, superior, and inferior thickness, [µm]) was tested via adjusted multivariate linear regression analysis.
Results
Mag explained 8% of variance in total PPAA change (F(1,29)=6.33, B=6.86, 95% CI: 1.29–12.44, p=0.018), 8% in superior PPAA change (F(1,29)=5.57, B=6.92, 95% CI: 0.92–12.92, p=0.025), and 7.1% in inferior PPAA change (F(1,29)=5.83, B=6.80, 95% CI: 1.04–12.56, p=0.022). Similarly, MagD explained 9.7% of variance in total PPAA change (F(1,29)=8.09, B=6.47, 95% CI: 1.82–11.13, p=0.008), 10% in superior PPAA change (F(1,29)=7.33, B=6.63, 95% CI: 1.62–11.63, p=0.011), and 8.5% in inferior PPAA change (F(1,29)=7.25, B=6.36, 95% CI: 1.53–11.18, p=0.012). MagD/Mag ratio and PPAA were not significantly associated.
Conclusion
To the best of our knowledge, this is the first study demonstrating a positive relationship between RGC dysfunction and retinal thickness changes between the superior and inferior hemispheres. The detection of asymmetrical structural loss, combined with functional RGC assessment using ssPERG, may be an informative tool for early glaucoma diagnosis.
... The ganglion cell analysis (GCA) algorithm on Cirrus HD-OCT can successfully detect the thickness of the macular ganglion cell-inner plexiform layer (GCIPL) [11]. GCIPL consists of nuclei and dendrites of RGCs, which accounts for up to 35% of the retinal thickness of the posterior pole, and therefore, it may be less prone to segmentation errors [12]. ...
Introduction:
To quantitatively assess retinal neurodegenerative changes with optical coherence tomography (Cirrus HD-OCT) in type 2 diabetes mellitus (T2DM) patients without diabetic retinopathy (DR), and evaluate their relationships with insulin resistance (IR) and associated systemic indicators.
Methods:
102 T2DM patients without DR and 48 healthy controls were included in this observational cross-sectional study. The OCT parameters of macular retinal thickness (MRT) and ganglion cell-inner plexiform layer (GCIPL) thicknesses were evaluated between diabetic and normal eyes. The receiver operating characteristics (ROC) curve was generated to evaluate the discrimination power of early diabetes. Correlation and multiple regression analysis were performed between ophthalmological parameters and T2DM -related demographic and anthropometric variables, and serum biomarkers and homeostasis model assessment of insulin resistance (HOMA-IR) scores.
Results:
MRT and GCIPL thicknesses showed significant thinning in patients, especially in inferotemporal area. High body mass index (BMI) correlated with decreased GCIPL thicknesses and elevated intraocular pressure (IOP). A negative correlation between waist-to-hip circumference ratio (WHR) and GCIPL thicknesses was also found. High-density lipoprotein (HDL) and fasting C-peptide (CP0) were associated with GCIPL thickness but only in inferotemporal region (r = 0.20, P = 0.04; r = -0.20, P = 0.05, respectively). Multiple regression analysis showed that increased HOMA-IR scores independently predicted both average (β = -0.30, P = 0.05) and inferotemporal (β = -0.34, P = 0.03) GCIPL thinning.
Conclusion:
Retinal thinning in early T2DM was associated with obesity-related metabolic disorders. IR as an independent risk factor for retinal neurodegeneration may increase the risk of developing glaucoma.
... The ganglion cells and their axons contribute to 30%-35% of the total retinal thickness in the macular area. 83 Parvocellular RGCs are the predominant subtype of RGCs in the macula and the parvocellular pathway has been suggested to be preferentially impacted by AD. 69,84 Accordingly, attention has focused on macular ganglion cell layer (GCL) thickness in AD. This review found varying results for GCL thickness measured by OCT. ...
Introduction:
We performed a systematic review and meta-analysis of the association between retinal imaging parameters and Alzheimer's disease (AD).
Methods:
PubMed, EMBASE, and Scopus were systematically searched for prospective and observational studies. Included studies had AD case definition based on brain amyloid beta (Aβ) status. Study quality assessment was performed. Random-effects meta-analyses of standardized mean difference, correlation, and diagnostic accuracy were conducted.
Results:
Thirty-eight studies were included. There was weak evidence of peripapillary retinal nerve fiber layer thinning on optical coherence tomography (OCT) (p = 0.14, 11 studies, n = 828), increased foveal avascular zone area on OCT-angiography (p = 0.18, four studies, n = 207), and reduced arteriole and venule vessel fractal dimension on fundus photography (p < 0.001 and p = 0.08, respectively, three studies, n = 297) among AD cases.
Discussion:
Retinal imaging parameters appear to be associated with AD. Small study sizes and heterogeneity in imaging methods and reporting make it difficult to determine utility of these changes as AD biomarkers.
Highlights:
We performed a systematic review on retinal imaging and Alzheimer's disease (AD).We only included studies in which cases were based on brain amyloid beta status.Several retinal biomarkers were associated with AD but clinical utility is uncertain.Studies should focus on biomarker-defined AD and use standardized imaging methods.
... The fea tures of glaucoma include pathological loss of retinal ganglion cells which are correlated to changes in the retinal nerve fiber layer (RNFL) and the optic nerve head. Considering that the RNFL and the ganglion cells constitute 30% to 35% of the macular retinal thickness and are thickest in the macular region, it was proposed that glaucomatous damage may be more readily detected in this region (2). To assess structural glaucomatous damage, earlier imaging technologies focused on the peripapillary RNFL, but only the recent advancement in optical coherence technology by spectral domain optical coherence to mography (SD-OCT) revived the idea of scanning the macular region. ...
Purpose: To evaluate the diagnostic ability of macular thickness parameters and peripapillary retinal nerve fiber layer (RNFL) thickness parameters for detecting glaucoma using spectral domain optical coherence tomography (SD–OCT). Methods: 37 eyes of 20 glaucoma patients and 30 eyes of 16 healthy subjects included in this study underwent macular and peripapillary RNFL scans with SD–OCT using standard scanning parameters. The ”Macular Cube 512x128” scan protocol was used to measure the macular thickness. The ”Optic Disc Cube 200x200” scan protocol was used for assessing the peripapillary region. The discrimination power of all parameters for detecting glaucoma was determined by the Area under Receiver Operating Characteristics (AROC) curve and sensitivity at fixed specificity, followed by a comparison of the best macular thickness and peripapillary RNFL thickness parameters. Results: Significant differences between glaucoma patients and healthy subjects were found in all peripapillary RNFL thickness parameters and all macular thickness parameters, except in the fovea (p=0.322). The largest AROC with sensitivity at >90% specificity among the peripapillary RNFL thickness parameters was found for the average peripapillary RNFL thickness (AROC 0.95, sensitivity 76%). The largest AROC with sensitivity at >90% specificity among the macular parameters was found for the inferior inner macular thickness (AROC 0.90, sensitivity 78%). There was no statistically significant difference between the AROCs of these two parameters (p=0.208). Conclusion: To discriminate glaucoma patients from healthy subjects using SD–OCT, macular thickness parameters had high diagnostic ability which was comparable to that of the peripapillary RNFL thickness parameters.
... Loss of RGC axons is apparent as characteristic ONH appearance or RNFL wedge defects, and therefore, loss of the RGCs may be assessed better directly by measurement of RGC layer thickness. As the cell body is substantially larger than the axons of the RGCs, it makes more part of the thickness than the axon does and, thus, might improve the ability to detect damage to these cells [8][9][10]. ...
Objective: Primary open-angle glaucoma (POAG), a neuro-ophthalmological disease, is a condition of slowly progressive loss of retinal ganglion cells which are evident as characteristic optic nerve head vicissitudes and visual field defects, only after death of more than 40% of cells. This huge loss when witnessed is started to treat only if the patient approaches an ophthalmologist with a significant complaint, leading to optic nerve head examination, which means being an asymptomatic disease, it is usually left undiagnosed until advanced. An additional system of diagnosis of the disease earlier in the stage can aid reduce the burden of the blindness of POAG. Methods: Among a total of 62 eyes of 31 subjects, 40 eyes of 20 POAG subjects, and 22 eyes of 11 age-matched healthy subjects were recruited. All of them underwent Spectral Domain Optical Coherence Tomography macular and optic disk scans to note macular ganglion cell–inner plexiform layer (mGCIPL) and retinal nerve fiber layer (RNFL) thicknesses. Statistical analysis was did using an unpaired t-test and calculating a two-tailed p value, in which the significance was indicated by p<0.05. Results: Similar to peripapillary RNFL thickness, the mGCIPL parameters, that is, minimum GCIPL thickness and GCIPL thickness in all sectors decreased significantly in POAG eyes to be able to discriminate them from normal. mGCIPL and RNFL thickness decreased as the severity of glaucoma increased. Conclusion: The minimum GCIPL thickness and that in all sectors can discriminate POAG eyes from healthy eyes significantly and has comparable performance to that of peripapillary RNFL thickness.
... Recent glaucoma studies have also paid attention to the macula as it has the highest density of the RGC. Vascular and functional measures of the inner macula may be a useful tool in assessment of glaucoma progression [12][13][14][15]. ...
Purpose
To evaluate the association between OCT-angiography (OCTA) and photopic negative response (PhNR) in open angle glaucoma (OAG) patients and assess the diagnostic accuracy of these parameters in early detection of glaucoma.
Methods
A total of 152 eyes were enrolled in this study, 28 eyes with mild POAG (group I), 44 eyes with moderate-severe POAG (group 2) & 80 eyes of healthy subjects (control group). Full ophthalmological examination, OCTA and PhNR measurements were underwent for all participants. RNFL, GCC thicknesses, PhNR (implicit time and amplitude) were recorded. The superficial and deep capillary plexus vessel density (SCP-VD%, DCP-VD%) were measured by using 6 × 6 mm macula OCTA scans. The peripapillary vessel density (RPC-VD %) were measured by using 4.5 × 4.5 mm optic disk head OCTA scans.
Results
There were reduction of the median Interquartile range (IQR) thickness of the GCC and RNFL in OAG eyes versus normal (P < 0.001). RPC-VD%, SCP-VD % and DCP-VD% were significantly reduced in OAG eyes versus normal (P < 0.001). Increased OAG severity was associated with more reduction in PhNR amplitude and increased implicit time. Reduced PhNR amplitude and prolonged latency were significantly correlated with reduced vascular parameters. The RCP-VD and PhNR amplitude demonstrated higher diagnostic accuracy (98.7) with the largest AUC and higher sensitivity and specificity (100% & 98.7%, respectively), followed by the PhNR implicit time with (AUC = 0.995) with a diagnostic accuracy 98.7. The SCP-VD, RNFL and GCC thickness had a diagnostic accuracy of (75.0, 81.6 & 84.2), respectively (P < 0.001).
Conclusions
OCTA vascular parameters displayed significant positive correlation with PhNR amplitude and significant negative correlation with PhNR implicit time. OCTA and PhNR parameters showed a high diagnostic accuracy for detection of glaucoma, and both may provide promising insight in early detection of glaucoma.
This study was retrospectively registered on ClinicalTrials.gov (identifier, NCT05104294).
... [? ] Zeimer and colleagues suggested that analyzing macular parameters may be used as an alternative or additional parameter to peripapillary RNFL thickness in diagnosing glaucoma. [7] It has been shown that macular thickness is correlated with optic disc cupping and RNFL thickness in diagnosing glaucoma. [8,9] Furthermore, macular thickness also correlates with RGC counts and perimetry parameters in both glaucomatous and normal eyes when diagnosing glaucoma and analyzing its progression. ...
Purpose:
Presence of diabetes in glaucoma patients may influence findings while documenting the progression of glaucoma. We conducted the study to compare individual and combined effects of diabetes and glaucoma on macular thickness and ganglion cell complex thickness.
Methods:
The present study is a cross-sectional analysis of 172 eyes of 114 individuals. The groups were categorized according to the following conditions: glaucoma, diabetes mellitus, both glaucoma and diabetes (`both' group), and none of these conditions (`none' group). Patients with diabetes did not have diabetic retinopathy (DR). We compared retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, foveal loss of volume (FLV), and global loss of volume (GLV) among the groups. We used random effects multivariate analysis to adjust for potential confounders.
Results:
The mean (SD) age of these individuals was 60.7 (10.1) years. The total average RNFL and GCC were significantly lower in the glaucoma group (RNFL: -36.27, 95% confidence intervals [CI]: -42.79 to -29.74; P < 0.05, and GCC: -26.24, 95% CI: -31.49 to -20.98; P < 0.05) and the `both' group (RNFL: -24.74, 95% CI: -32.84 to -16.63; P < 0.05, and GCC: -17.92, 95% CI: -24.58 to -11.26; P < 0.05) as compared with the `none' group. There were no significant differences in the average RNFL values and total average GCC between the diabetes group and the `none' group. The values of FLV and GLV were significantly higher in the `glaucoma' group and the `both' group as compared with the `none' group. The foveal values were not significantly different across these four groups. Among the glaucoma cases, 25% were mild, 30% were moderate, and 45% were severe; there was no significant difference in the proportion of severity of glaucoma between the `glaucoma only' and `both' groups (p=0.32). After adjusting for severity and type of glaucoma, there were no statistically significant differences in the values of average RNFL (6.6, 95% CI: -1.9 to 15.2; P=0.13), total average GCC (3.6, -95% CI: -2.4 to 9.6; P=0.24), and GLV (-3.9, 95% CI: -9.5 to 1.6; P=0.16) in the `both group' as compared with the glaucoma only group.
Conclusion:
We found that diabetes with no DR did not significantly affect the retinal parameters in patients with glaucoma. Thus, it is less likely that thickness of these parameters will be overestimated in patients with glaucoma who have concurrent diabetes without retinopathy.
... The idea that the macula is a good site to test for glaucomatous changes has gradually become more acceptable over the years. Landmark studies by Zeimer, [11][12][13][14][15][16] Asrani and colleagues have demonstrated damage in the 17,18 macula and showed that evaluation of the macula may be more effective for detecting early glaucoma than evaluation in the peri-papillary region. Macular evaluation for glaucoma is centred around the GCC, which has been reported to be damaged early in glaucoma. ...
Aim: To evaluate the differences between ganglion cell complex (GCC) of primary open angle glaucoma and ocular disorders affecting the macula. Methods and Materials: Forty-seven patients diagnosed with primary open angle glaucoma and 27 patients with macular diseases of different aetiology were enrolled in this pilot study. All patients underwent direct GCC analysis with the optical coherence tomographic scan, using the Optovue Fourier Domain RTVue-version. A comparison of the average GCC thickness, focal loss volume (FLV) and the global loss volume (GLV) of the two groups was made. Results: A total of 74 pairs of eyes were included in the study. This comprised 48 males and 26 females with a mean age of 53.8 ± 11.3 among glaucoma patients and 59.8 ± 9.8 among patients with macular disease. Eyes with macular disease (33.3%) and eyes with glaucoma (42.6%) had abnormal average GCC parameters. However, the mean average GCC value was significantly higher in eyes with macular disease (87.50 ± 20.73) when compared with eyes with glaucoma (76.55 ± 12.51) (p=0.01). A significantly higher percentage of eyes with macular disease (43.3%) had GLV values within normal range when compared with eyes with glaucoma (21.3%) (p=0.03). Abnormal FLV values were seen in both eyes with macular disease (83.3%) and eyes with glaucoma (80.9%) but the differences were not of statistical significance (p= 0.24). Conclusion: This pilot study demonstrated abnormal OCT GCC values in eyes with glaucoma as well as in eyes with macular disease. However, eyes with macular disease had significantly higher mean average GCC parameters but GLV parameters that were within normal values.
... Optical coherence tomography (OCT) makes it possible to image and segment the multilayered structure of the macula. Because approximately 40% of retinal ganglion cells (RGCs) are located within the macula 1 , there has been a recent focus on macular OCT imaging to measure the reduction in the thickness of inner retinal layers caused by glaucoma [2][3][4] , in manner that approximates histological analysis 5 . Loss of RGCs also results in loss of visual field (VF) sensitivity estimated with standard automated perimetry. ...
Correlation between structural data from optical coherence tomography and functional data from the visual field may be suboptimal because of poor mapping of OCT measurement locations to VF stimuli. We tested the hypothesis that stronger structure–function correlations in the macula can be achieved with fundus-tracking perimetery, by precisely mapping OCT measurements to VF sensitivity at the same location. The conventional 64 superpixel (3° × 3°) OCT grid was mapped to VF sensitivities averaged in 40 corresponding VF units with standard automated perimetry (conventional mapped approach, CMA) in 38 glaucoma patients and 10 healthy subjects. Similarly, a 144 superpixel (2° × 2°) OCT grid was mapped to each of the 68 locations with fundus-tracking perimetry (localized mapped approach, LMA). For each approach, the correlation between sensitivity at each VF unit and OCT superpixel was computed. Vector maps showing the maximum correlation between each VF unit and OCT pixel was generated. CMA yielded significantly higher structure–function correlations compared to LMA. Only 20% of the vectors with CMA and < 5% with LMA were within corresponding mapped OCT superpixels, while most were directed towards loci with structural damage. Measurement variability and patterns of structural damage more likely impact correlations compared to precise mapping of VF stimuli.
... A correlation was found between macular thickness and pRNFL thickness and optic cupping [45,46]. Humphrey visual field (HVF) and RGC count also correlated with macular thickness in normal and glaucomatous subjects [47][48][49]. The analysis of pRNFL only concentrates on a ring of tissues nearby an optic nerve; however, macular imaging allows a complete macular thickness and volume. ...
Glaucoma is a progressive and degenerative optic neuropathy that causes severe visual impairment or even blindness if left untreated. Glaucoma is majorly caused due to stress which increases intraocular pressure that leads towards optic nerve degeneration. The degenerative optic nerve then causes irreversible loss of peripheral vision which may lead to complete blindness. Although the progression of glaucoma can harshly affect the vision, it can be prevented if diagnosed in the early stages. However, optical coherence tomography (OCT) imagery is widely used by ophthalmologist for early glaucoma diagnosis and progression tracking. Owing to this objective screening capacity of the OCT imagery, many researchers have used it as an examination procedure to verify their clinical studies or to train their autonomous systems for mass-screening glaucomatous pathologies. In this paper, we present a systematic review of the recent studies that have proposed various solutions to mitigate glaucomatous progression using OCT imagery. Initially, we have presented a review of clinical studies that looked at glaucomatous diseases in OCT images.Furthermore, this paper presents a detailed survey of the state-of-the-art techniques for glaucoma detection and grading. In future directions, ganglion cell layer as well as macular analysis and its automation will improve the diagnostic power of OCT for the early glaucoma detection and especially monitoring its progression.
... 7 Bundan dolayı maküla, glokomatöz değişikliklerin değerlendirilmesi için stratejik bir bölgedir. 8,9 Bu çalışmada amaç XFS'deki olası erken vasküler değişikliklerin araştırılmasıdır. Yapısal hasarı rutin testlerle tespit edemediğimiz XFS'li olgularda erken vasküler hasarın OKTA ile değerlendirilebilmesi bu hastalardaki glokoma dönüşüm riskini öngörebilir. ...
Amaç: Bu çalışmada, eksfolyasyon sendromu olgularında ve sağlıklı kontrol grubunda maküla damar dansitesinin karşılaştırılması hedeflendi. Gereç ve Yöntem: Eksfolyasyon sendromlu 30 hastanın ve 26 sağlıklı kontrolün birer gözü çalışmaya dahil edildi. Yüzeyel maküla damar dansitesi ve iç maküla (retina sinir lifi tabakası+gangliyon hücre tabakası+inner pleksiform tabakası) kalınlığı değerleri 6x6 milimetrelik maküla optik koherans tomografi anjiyografi görüntüleri ile değerlendirildi. Tüm görüntü ve inferior, nazal, superior, temporal kadran yüzeyel perifoveal damar dansitesi ölçümleri çalışmaya dahil edilmiştir. Bulgular: Gruplar cinsiyet, yaş, göz içi basıncı, sinyal gücü indeksi ve aksiyel uzunluk yönünden benzerlerdi (hepsi için p>0,05). İki grup arasında ortalama iç maküla kalınlıkları tüm sektörlerde benzerdi (hepsi için p>0,05). Ancak eksfolyasyon sendromlu olan gözler kontrollerle karşılaştırıldığında tüm görüntü bölgesinde ve temporal perifoveal bölgede azalmış yüzeyel maküla damar dansitesi gözlendi (sırasıyla p<0,001, p=0,01). Sonuç: Eksfolyasyon sendromlu hastalarında sağlıklı kontrollere kıyasla iç maküla kalınlıkları korunmuş olmasına rağmen maküla damar dansitesi değerleri azalmış izlendi. Bu bulgu, vasküler değişikliklerin yapısal değişikliklerden daha erken meydana gelebileceği ve eksfolyasyon sendromlu patogenezinde önemli bir role sahip olabileceği görüşünü desteklemektedir. İleri mikrovasküler sistem görüntü-lemesi, eksfolyasyon sendromlu hastalarda erken değişiklikleri saptamaya yardımcı olabilir. Objective: To compare the macula vessel density in patients with exfoliation syndrome and healthy controls. Material and Method: One eye was included from 30 patients with exfoliation syndrome and 26 healthy controls. The superficial macula vessel density and the inner macula (retina nerve fiber layer layer+ganglion cell layer+inner plexiform layer) thickness values were evaluated with 6x6 mm optical coherence tomography angiography scans. The whole image and inferior, nasal, superior, temporal quadrant superficial vessel density's in the perifoveal region were evaluated in the present study. Results: The age, sex, intraocular pressure, signal strength index and axial length were similar between groups (p>0.05 for all). The mean inner macula thicknesses of the groups were similar in all sectors (p>0.05 for all). However, eyes with exfoliation syndrome demonstrated reduced mean superficial perifoveal macula vessel density's in the whole image region and the temporal sector compared with the controls (p<0.001, p=0.01, respectively). Conclusions: The macula vessel density values were diminished despite preserved inner macula thicknesses in exfoliation syndrome compared with healthy controls. This supports that vascular alterations may occur earlier than structural alterations and may have an important role in the pathogenesis of exfoliation syndrome. Advanced imaging of microvasculature may help to discriminate early changes in exfoliation syndrome.
... Recent glaucoma studies have also paid attention to the macula as it has the highest density of the RGC. Vascular and functional measures of the inner macula may be a useful tool in assessment of glaucoma progression [12][13][14][15]. ...
Purpose: To evaluate the association between OCT-angiography (OCTA) and photopic negative response (PhNR) in open angle glaucoma (OAG) patients and assess the diagnostic accuracy of these parameters in early detection of glaucoma.
Methods: A total of 152 eyes were enrolled in this study. 28 eyes with mild POAG (group I), 44 eyes with moderate-severe POAG (group 2) & 80 eyes of healthy subjects (control group). Full ophthalmological examination, OCTA and PhNR measurements were underwent for all participants. RNFL, GCC thicknesses, PhNR (implicit time and amplitude) were recorded. The superficial and deep capillary plexus vessel density (SCP-VD%, DCP-VD %) were measured by using 6×6mm macula OCTA scans. The peripapillary vessel density (RPC-VD %) were measured by using 4.5×4.5mm optic disc head OCTA scans.
Results: There were reduction of the median Interquartile range (IQR) thickness of the GCC and RNFL in OAG eyes versus normal (P<0.001). RPC-VD%, SCP-VD % and DCP-VD% were significantly reduced in OAG eyes versus normal (P<0.001). Increased OAG severity was associated with more reduction of PhNR amplitude and increased implicit time. Reduced PhNR amplitude and prolonged latency were significantly correlated with reduced vascular parameters. The RCP-VD and PhNR amplitude demonstrated higher diagnostic accuracy (98.7) with the largest AUC and higher sensitivity and specificity (100% & 98.7%, respectively), followed by the PhNR implicit time with (AUC=0.995) with a diagnostic accuracy 98.7. The SCP-VD, RNFL and GCC thickness had a diagnostic accuracy of (75.0, 81.6 & 84.2) respectively (P<0.001).
Conclusions: OCTA vascular parameters displayed significant positive correlation with PhNR amplitude and significant negative correlation with PhNR implicit time. OCTA and PhNR parameters showed a high diagnostic accuracy for detection of glaucoma, and both may provide promising insight in early detection of glaucoma.
This study was retrospectively registered on ClinicalTrials.gov (identifier, NCT05104294).
... OCT has been widely used in ophthalmology clinics and research for its excellent depth-resolved capability [9]. For instance, the retinal thickness, as a reflection of total cell number and retinal structure complexity, has been used as a biomarker for retinal degeneration [10][11][12] and damage recovery [13,14] studies. Retinal layer thickness abnormity has also been associated with retinopathy of prematurity (ROP). ...
A better study of postnatal retinal development is essential for the in-depth understanding of the nature of the vision system. To date, quantitative analysis of postnatal retinal development is primarily limited to endpoint histological examination. This study is to validate in vivo optical coherence tomography (OCT) for longitudinal monitoring of postnatal retinal development in developing mouse eyes. OCT images of C57BL/6J mice were recorded from postnatal day (P) 14 to P56. Three-dimensional (3D) frame registration and super averaging were adopted to investigate the fine structure of the retina. Quantitative OCT analysis revealed distinct outer and inner retinal layer changes, corresponding to eye development. At the outer retina, external limiting membrane (ELM) and ellipsoid zone (EZ) band intensities gradually increased with aging, and the IZ band was detectable by P28. At the inner retina, a hyporeflective layer (HRL) between the nerve fiber layer (NFL) and inner plexiform layer (IPL) was observed in developing eyes and gradually disappeared with aging. Further image analysis revealed individual RGCs within the HRL layer of the young mouse retina. However, RGCs were merged with the NFL and the IPL in the aged mouse retina. Moreover, the sub-IPL layer structure was observed to be gradually enhanced with aging. To interpret the observed retinal layer kinetics, a model based on eyeball expansion, cell apoptosis, and retinal structural modification was proposed.
... OCT has been widely used in ophthalmology clinics and research for its excellent depth-resolved capability [10]. For instance, the retinal thickness, as a reflection of total cell number and retinal structure complexity, has been used as a biomarker for retina degeneration [11][12][13], and damage recovery [14,15] studies. Retinal layer thickness abnormity has been also associated with retinopathy of premature (ROP). ...
A better study of the postnatal retinal development is not only essential for the in-depth understanding of the nature of the vision system but also may provide insights for treatment developments of eye conditions, such as retinopathy of premature (ROP). To date, quantitative analysis of postnatal retinal development is primarily limited to end-point histological examination. This study is to validate in vivo optical coherence tomography (OCT) for longitudinal monitoring of postnatal retinal development in developing mouse eyes. Three-dimensional (3D) frame registration and super averaging were adopted to investigate the fine structure of the retina. Interestingly, a hyporeflective layer (HRL) between the nerve fiber layer (NFL) and inner plexiform layer (IPL) was observed in developing eyes and gradually disappeared with aging. To interpret the observed retinal layer kinetics, a model based on eyeball expansion, cell apoptosis, and retinal struc-tural modification was proposed.
... Currently, in clinical practice, physicians generally focus on characteristics indicating neural tissue loss in the ONH and its ambient areas when assessing changes in the structure of glaucomatous eyes. Nevertheless, although alterations occur in the ONH and cpRNFL, the macula is suggested to be an assessment location for glaucoma [12]. Only a few large vessels exist in the macula, and the shape is normally less variable than that of the ONH. ...
Backgroud: The retinal microvasculature within the macula in glaucomatous eyes is not clear.
Objectives:
To detect macular vessel density (MVD) changes in primary angle closure glaucoma (PACG).
Methods:
22 PACG patients who had an episode of acute primary angle closure were included. Structural optical coherence tomography (OCT) scans were conducted to measure the thickness of the peripapillary retinal nerve fiber layer and macular ganglion cell complex (GCC). The MVD was measured with OCT angiography.
Results:
A weakened macular microvascular network that had an expanded fovea avascular zone was observed in the case group. Compared with the control group, the case group had a lower MVD (P < 0.001). Single correlation analysis revealed a significant correlation of the MVD with best-corrected visual acuity （BCVA） (r = -0, 65, P = 0.001), GCC (r = 0.50, P = 0.018), and the visual field mean deviation (r = -0.54, P= 0.009) in the case group. Moreover, in the mixed-effect models, the MVD was found to be positively correlated with GCC (P= 0.017), and negatively correlated with LogMar BCVA (P < 0.001).
Conclusions:
After an acute angle closure attack, the macular microvascular network is attenuated, and the MVD decreases significantly.
... Approximately 30% to 50% of the retinal ganglion cells (RGC) may be lost before detectable visual field deficits occur in glaucoma. 4,5 Zeimer et al 6 suggested that, since ganglion-cell-inner-plexiform layer (GCIPL) and RNFL constitute 30-35% of the total macular thickness, the macular thinning in glaucoma could be attributed to reduction in GCIPL thickness. Conversely, any loss of tissue in this region could be a sign of glaucomatous damage. ...
Purpose
To determine whether macular volume and macular GCA measurements in patients are comparable to their RNFL thickness parameters.
Materials and Methods
The cross-sectional, observational study was conducted on 1380 eyes with 460 each, into three groups. Group I: patients with healthy eyes. Group II: patients diagnosed as pre-perimetric glaucoma. Group III: patients with diagnosed perimetric glaucoma. After patients were selected on the basis of inclusion and exclusion criteria, baseline standard ophthalmic examination was done by the same operator under the same settings, including SD-OCT using both the Spectralis SD-OCT and the Cirrus SD-OCT as elaborated below.
Statistical Analysis
Data were checked for normality before statistical analysis using Shapiro–Wilk test. Normally distributed continuous variables were compared using ANOVA. For all statistical tests, a p < 0.05 was taken to indicate a significant difference. Receiver operating characteristic (ROC) curves were used to define the ability RNFL and GCC parameters to distinguish perimetric and preperimetric glaucomatous eyes from control eyes.
Results
There was a statistically significant difference in the average, superior, inferior RNFL thickness and average, superior, inferior GCIPL thickness between Group I and Group II (p<0.001), between Group I and Group III (p<0.001) and also between Group II and Group III (p<0.001). The statistical significance was also reflected in their AUROCs.
Conclusion
Mean, superior, inferior GCIPL thickness along with macular volume analysis can substantiate RNFL analysis for diagnosis, serial monitoring and follow-up of glaucoma patients and suspects.
... In 1998, Zeimer et al. [5] first proposed that changes in retinal thickness at the macula may be an indicator of the structural damage in NTG based on the anatomic evidence that almost half of the RGCs are aggregated in the macular region. Since then, many studies have put the macular analysis to the test [6][7][8]. ...
Purpose:
This study aimed to compare the clinical characteristics of patients who showed structural progression in the peripapillary retinal nerve fiber layer (RNFL) first against those who showed progression in the macular ganglion cell-inner plexiform layer (GCIPL) first and to investigate clinical parameters that help determine whether a patient exhibits RNFL or GCIPL damage first.
Methods:
A retrospective review of medical records of patients diagnosed with early-stage normal-tension glaucoma was performed. All eyes underwent intraocular pressure measurement with Goldmann applanation tonometer, standard automated perimetry, and Cirrus optical coherence tomography at 6-month intervals. Structural progression was determined using the Guided Progression Analysis software. Blood pressure was measured at each visit.
Results:
Forty-one eyes of 41 patients (mean age, 52.6 ± 16.7 years) were included in the study. In 21 eyes, structural progression was first detected in the RNFL at 54.2 ± 14.8 months, while structural progression was first observed at the macular GCIPL at 40.5 ± 11.0 months in 20 eyes. The mean intraocular pressure following treatment was 13.1 ± 1.8 mmHg for the RNFL progression first group and 13.4 ± 1.8 mmHg for the GCIPL progression first group (p = 0.514). The GCIPL progression first group was older (p = 0.008) and had thinner RNFL at baseline (p = 0.001). The logistic regression analyses indicated that both age and follow-up duration until first progression predicted the region of structural progression (odds ratio, 1.051; 95% confidence interval, 1.001-1.105; p = 0.046 for age; odds ratio, 0.912; 95% confidence interval, 0.840-0.991; p = 0.029 for time until progression).
Conclusions:
Age of glaucoma patients and time until progression are associated with the region of the first structural progression in normal-tension glaucoma. Further studies exploring the association between glaucomatous progression and the location of damage are needed.
... [9][10][11] Evaluation of macular thickness with OCT has been proposed as a parameter for diagnosis and monitoring of glaucoma, as the macula has the highest RGC density. 12,13 Although central vision is often preserved until the late stages of glaucoma, it is known that glaucomatous damage can affect the macula in the early stages of the disease, preceding the onset of a glaucomatous VF defect. [14][15][16][17][18][19][20] At the opposite end of the spectrum, in advanced glaucoma, circumpapillary RNFL (cRNFL) reaches a thickness at which no more thinning is evidentthe floor effect. ...
Purpose
To evaluate differences in the thickness of the individual macular layers between early, moderate, and severe glaucomatous eyes and compare them with healthy controls.
Patients and Methods
Subjects with glaucoma presenting typical optic nerve head findings, high intraocular pressure with or without visual field (VF) damage and normal controls were included. All participants underwent 24–2 perimetry and spectral-domain OCT. Patients were divided into three groups (early, moderate, and severe) based on the mean deviation of the VF and a healthy control group. The device segmented the layers automatically, and their measurements were plotted using the means of the sectors of the inner (3mm) and outer (6mm) circles of the ETDRS grid.
Results
A total of 109 eyes qualified for the study: 14 in the control group and 52, 18 and 25 in the early, moderate and severe groups, respectively. Mean age was 66.13 (SD=12.38). The mean thickness of the circumpapillary retinal nerve fiber layer (RNFL), total macular thickness (TMT), macular RNFL, ganglion cell layer (GCL) and inner plexiform layer (IPL) were significantly different between the 4 groups, with progressive decrease in thickness. Significant overall difference was found for the inner nuclear layer (INL), and the severe glaucoma group presented thicker measurements than controls and early glaucoma. Outer nuclear layer (ONL) was thinner in severe glaucoma group compared with early glaucoma group.
Conclusion
Individual macular layer measurement using the inner and outer circles of the ETDRS grid is useful to evaluate different stages of glaucoma. The INL thickening and ONL thinning in advanced glaucoma should be explored in the future studies.
... Using a Retinal Thickness Analyzer (Talia Technology Ltd, Neve Ilan, Isel) Zeimer et al. first hypothesized the possibility to detect the loss of ganglion cells analysing the posterior pole [23]. Following the introduction of timedomain OCT, Greenfield et al. observed a reduction of macular thickness in early-and moderate-stage glaucoma by using time-domain OCT and demonstrated that these macular changes were correlated with VF sensitivity [13]. ...
Optical Coherence Tomography (OCT) is a powerful instrument for helping clinicians detect and monitor glaucoma. The aim of this study was to provide a detailed mapping of the relationships between visual field (VF) sensitivities and measures of retinal structure provided by a commercial Spectral Domain (SD)-OCT system (RTvue-100 Optovue).
Sixty-three eyes of open angle glaucoma patients (17 males, 16 females, and mean age 71 ± 7.5 years) were included in this retrospective, observational clinical study. Thickness values for superior and inferior retina, as well as average values, were recorded for the full retina, the outer retina, the ganglion cell complex, and the peripapillary retinal nerve fiber layer (RNFL). RNFL thickness was further evaluated along eight separate sectors (temporal lower, temporal upper, superior temporal, superior nasal, nasal upper, nasal lower, inferior nasal, and inferior temporal). Point-wise correlations were then computed between each of these OCT measures and the visual sensitivities at all VF locations assessed via Humphrey 10-2 and 24-2 perimetry. Lastly, OCT data were fit to VF data to predict glaucoma stage.
The relationship between retinal thickness and visual sensitivities reflects the known topography of the retina. Spatial correlation patterns between visual sensitivities and RNFL thickness along different sectors broadly agree with previously hypothesized structure–function maps, yet suggest that structure–function maps still require more precise characterizations. Given these relationships, we find that OCT data can predict glaucoma stage.
Ganglion cell complex and RNFL thickness measurements are highlighted as the most promising candidate metrics for glaucoma detection and monitoring.
... Research has found that imaging the retinal thickness loss in the macula is a sensitive measure for detecting early glaucoma. 11 • Diagnosis and scanning protocol for macular OCT. Each of the three OCT devices provides a different scan of the macula (Examples appear in Table 1). ...
Since glaucoma is a progressive disease, physicians are constantly searching for reliable tools to monitor it over time. Before the introduction of optical coherence tomography, determination of glaucoma progression relied heavily on clinical assessment of the optic nerve, comparison of disc photos over time and visual field analysis. Although these remain key elements of the glaucoma evaluation, they’re still subjective and qualitative in nature, limiting their ability to detect progression reliably. In this article, we’ll provide tips on how to use the OCT devices we’re familiar with to monitor progression, and how to avoid artifacts and other errors that can lead you astray.
Clinical relevance:
Alterations in ocular microvasculature may contribute to pathogenesis of exfoliation glaucoma (XFG) and may improve monitoring this aggressive type of open angle glaucoma.
Background:
This work aims to compare the macula vessel density and the relationship between macula vessel density and central visual field mean sensitivity between eyes with XFG and eyes with primary open-angle glaucoma (POAG) of different stages.
Methods:
In this cross-sectional observational study, the macula vessel density values were compared among 52 POAG cases (26 early stage, 26 moderate to advanced stage) and 53 XFG cases (27 early stage, 26 moderate to advanced stage). The vessel density values were evaluated with optical coherence tomography angiography. Vasculature-function and structure-function relationships were analysed by comparing macula vessel density, inner macula thickness and visual field mean sensitivity in early and moderate to advanced stages of XFG and POAG eyes separately.
Results:
The early stage XFG eyes had a significantly lower global macula vessel density compared with early stage POAG eyes (42.81 ± 3.85% and 46.56 ± 3.90%, respectively; p = 0.02). However, the tendency of XFG eyes for a lower vessel density compared with the POAG eyes did not exhibit any significance in moderate to advanced stages of glaucoma (37.39 ± 5.65% and 38.35 ± 4.67%, respectively; p = 0.9). The macula vessel density (%)-visual field mean sensitivity (1/Lambert) correlation was statistically significant in early stage XFG eyes (r = 0.464 p = 0.01), while no such correlation was notable for the early stage POAG eyes (r = -0.029 p = 0.89).
Conclusion:
The macula vessel density appears to be more severely affected in early stage XFG than POAG of similar severity, suggesting a relatively greater value of vascular insufficiency in XFG. The significant vasculature-function association in early stage XFG, which was absent in early stage POAG, may infer the importance of macula vessel density in monitoring functional loss in early stages of XFG.
Prcis:
SD-OCT facilitates early glaucoma detection in the Chinese population in Taiwan. The best parameters for POAG, PACG, NTG, and GS detection are temporal inferior BMO-MRW, inner temporal mGCL, temporal superior cpRNFL, and mean global BMO-MRW, respectively.
Purpose:
We investigated the diagnostic capability of spectral-domain optical coherence tomography (SD-OCT) for different types of early glaucoma among the Chinese population in Taiwan.
Methods:
One eye each was assessed from 113 individuals with healthy eyes, 125 individuals with suspected glaucoma (GS), and 156 patients with early glaucoma (primary open-angle glaucoma [POAG], 87; primary angle-closure glaucoma [PACG], 50; and normal-tension glaucoma [NTG], 19). Circumpapillary (cp) retinal nerve fiber layer (RNFL) thickness (global and sectoral); Bruch's membrane opening-minimum rim width (BMO-MRW); and macular parameters, including the macular RNFL (mRNFL), macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL), were assessed using SD-OCT. The areas under receiver operator characteristic curves (AUCs) were calculated to evaluate the diagnostic capacity of the parameters to differentiate between healthy and early glaucomatous eyes.
Results:
The parameters most suitable for detecting early POAG, PACG, NTG and GS were temporal inferior BMO-MRW (AUC, 0.847), inner temporal mGCL (AUC, 0.770), temporal superior cpRNFL (AUC, 0.861) and mean global BMO-MRW (AUC, 0.768), respectively. Among the macular parameters, mGCL exhibited the highest diagnostic capacity. The diagnostic capacity of mGCL was lower than that of cpRNFL and BMO-MRW for POAG and NTG but not PACG. After adjusting for confounding variables in multivariable analysis, the AUC was determined to be 0.935 for POAG and 0.787 for GS.
Conclusion:
SD-OCT facilitates the detection of early POAG, PACG and NTG. Using a combination of cpRNFL, BMO-MRW and macular parameters may enhance their diagnostic capacities. Further studies are necessary to validate these findings.
PURPOSE
: We compared ganglion cell layer (GCL) and inner plexiform layer (IPL) rates of change (RoC) in patients with suspected (GS) and established glaucoma (EG) to test the hypothesis that IPL thickness changes occur earlier than GCL in eyes with early damage.
DESIGN
: Prospective, cohort study.
METHODS
: 64 GS eyes (46 patients) and 112 EG eyes (112 patients) with ≥2 years of follow-up and ≥3 macular optical coherence tomography scans were included. GCL and IPL superpixel thickness measurements were exported. A Bayesian hierarchical model with random intercepts/slopes, and random residual variances was fitted to estimate RoC in individual superpixels. Normalized RoC and proportions of superpixels with significantly negative and positive GCL and IPL RoC were compared within the groups.
RESULTS
: Average (SD) follow-up time and number of scans were 3.5 (0.7) years, and 4.2 (1.0), respectively, in the GS group and 3.6 (0.4) years and 7.3 (1.1) in the EG group. Mean (SD) normalized RoC was faster for GCL than IPL (−0.69 [0.05] vs. −0.33 [0.04]) in the GS group, whereas it was faster for IPL (−0.47 [0.03] vs. −0.28 [0.02]) in EG eyes. GCL RoC were significantly negative in 24/36 superpixels compared with 8/36 for IPL (p<0.001) in GS eyes. In the EG group, 23/36 superpixels had significant negative IPL RoC compared to 13/36 superpixels for GCL (p=0.006).
CONCLUSIONS
: GCL thickness was more likely to demonstrate change compared to IPL in glaucoma suspects. There is no evidence of preferential IPL thinning in eyes with suspected early glaucoma damage.
PurposeTo investigate the macular spectral domain optical coherence tomography (SD-OCT) measurements of the segmented inner retinal layers in patients with exfoliation syndrome (XFS), exfoliation glaucoma (XFG).Methods
This prospective cross-sectional study included 28 eyes with XFS, 47 eyes with XFG, and 29 healthy controls. Thickness of the inner retinal layers, including retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) was obtained from the horizontal SD-OCT scans. Functional correlation of structural parameters was analyzed using the mean sensitivity (MS) values on 10–2 visual fields.ResultsThe RNFL, GCL, and IPL were thinnest in eyes with XFG. Among these retinal layers, IPL was significantly thinner in eyes with XFS than healthy controls (p = 0.02) and the IPL thickness was significantly correlated with the corresponding MS scores on 10–2 visual fields (r = 0.492, p = 0.02) in eyes with XFS. Neither GCL nor RNFL thickness values demonstrated significant correlations with functional parameters in eyes with XFS (r = 0.377, p = 0.08; r = 0.212, p = 0.34). In eyes with XFG, the IPL thickness correlated with the visual field MS scores (r = 0.572, p = 0.0007), similar to the correlation of GCL (r = 0.585, p = 0.0005) thickness with visual field scores.Conclusions
Segmented analysis of the macular IPL thickness presented a significant correlation with the 10–2 visual field scores not only in eyes with XFG but also in eyes with XFS. With respect to early dendritic/synaptic alterations in animal models, larger and longitudinal studies are encouraged to determine the predictive value of the IPL thickness for conversion of XFS to XFG.
Importance:
Ganglion cell analysis (GCA) of ocular coherence tomography (OCT) imaging is routinely used to detect and monitor glaucomatous damage of the ganglion cell complex in the macula. The GCA printout provides qualitative and quantitative data about the macular ganglion cell-inner plexiform layer and a single B-scan of the retina through the fovea. However, the full macular cube scan, including all 128 B-scans, is available for review. The macular cube scan provides considerable information about nonglaucomatous ocular pathology that may be missed if clinicians review only the GCA printout.
Objective:
To determine the frequency and type of nonglaucomatous macular findings that are observable in the full macular cube scan but not the GCA printout.
Design, setting, and participants:
A retrospective cross-sectional analysis of GCA printouts and full macular cube scans to detect nonglaucomatous macular pathology at a tertiary care academic center. Consecutive patients undergoing ganglion cell complex imaging during routine glaucoma evaluations over a 1-week period in a multi-clinician glaucoma clinic.
Main outcomes and measures:
The prevalence and type of nonglaucomatous macular pathology visible on the GCA printout or macular cube scan.
Results:
Among 105 patients (mean (SD) age, 67 (15.46) years; 63 [60%] female and 42 [40%] male) 201 eyes were imaged (64 [31.7%] with suspected glaucoma, 126 [62.4%] with open-angle glaucoma, 6 [3.0%] with closed-angle glaucoma, and 6 [3.0%] with other glaucoma). GCA printouts and macular cube scans revealed nonglaucomatous macular pathology in 65 eyes (32.2%). Of these, 25 eyes (38.5%) included findings that were not visible on the GCA printout. Of the cases not visible on the printout, 16 eyes (64.0% ) included macular pathology that required further evaluation.
Conclusions and relevance:
The findings indicate that nonglaucomatous macular pathology may be missed based on GCA printouts alone. While it may be beneficial to review the full macular cube to detect potentially vision-threatening disease and ensure proper patient care, this study cannot determine if this missed pathology affects clinical outcomes.
Precis:
The macular and peripapillary structural and vascular alterations in elderly patients with age-related choroidal atrophy may mimic glaucomatous degeneration.
Purpose:
To evaluate the peripapillary retinal nerve fiber layer (pRNFL), macular nerve fiber layer (mNFL), ganglion cell layer (mGCL), inner plexiform layer (mIPL) thicknesses, and choroidal vascularity index (CVI) values in patients with age-related choroidal atrophy (ARCA) and to compare with the those of age and sex-matched healthy controls.
Methods:
The cross-sectional, observational study included 95 eyes of 95 patients. The patients were divided into two groups according to subfoveal choroidal thickness (sCT) values. Forty eight eyes with sCT<125 µm constituted ARCA group (group 1), and 47 eyes with sCT>125 µm constituted control group (group 2). Peripapillary RNFL, mNFL, mGCL, mIPL, sCT values and fundus autofluorescence images were acquired with spectral domain-optical coherence tomography (SD-OCT). Enhanced depth imaging mode SD-OCT images were binarized to show the luminal and stromal areas of choroid. CVI (%) was defined as the ratio of the luminal area to the total choroidal area with defined borders.
Results:
The mean age was 78.47±6.07 years in group 1 and 76.95±6.68 years in group 2. The mean, superior and inferior quadrants pRNFL thicknesses were significantly lower in group 1 than in group 2 (P<0.05 for all). The mean mNFL, mGCL, mIPL thickness values were also statistically lower in group 1 than group 2 (P<0.05 for all). The CVI value was 61.29±4.52 in group 1, and 64.81±3.80 in group 2 (P<0.001).
Conclusion:
The patients with ARCA had decreased pRNFL, inner macular layer thickness and CVI values when compared to healthy control eyes. These findings should be considered in the differential diagnosis and the follow up of eyes with glaucoma.
Purpose: Evaluation of ganglion cell complex measurement and the use of parameters of lamina cribrosa depth in early diagnosis and progression of patients with suspected glaucoma.
Materials and Methods: Measurements were taken with Heidelberg Spectralis Spectral Domain Optical Coherence Tomography from patients in both groups. Ganglion cell complex thicknesses measured with segmentation analysis. Lamina cribrosa depths were measured by using optic nerve head images of the glaucoma suspected group and the control group.
Results: Thirty-one glaucoma suspect patients and 42 healthy individuals were included in the study. The thickness of the ganglion cell layer was 11.46 in the glaucoma suspect group, and it was 12.19 in the control group. Mean lamina cribrosa depth was 579.3 in the glaucoma suspected group and 399.62 in the control group.
Conclusion: Optical coherence tomography helps ophthalmologists for the diagnosis and follow-up of glaucoma patients, and non-invasively measured ganglion cell layer and lamina cribrosa depth may be a guide for early diagnosis. In this study, lamina cribrosa depth difference is more significant in the glaucoma suspect group so this parameter can be used in early diagnosis.
The last three decades have been a turning point for early glaucoma diagnosis and monitoring by newly developed imaging techniques. Improvements in imaging of the anterior segment (AS), retinal nerve fiber layer (RNFL), optic nerve head (ONH), and macular ganglion cell complex (GCC) came into existence and broke new ground for early diagnosis and progression survey. This review will summarize the different ophthalmic imaging techniques, their principles, pros and cons, ongoing development processes, and the future of imaging methods. The aim is to provide the clinician with an understanding of the role of imaging methods and provide insight for appropriate use and evaluation of their outputs in glaucoma diagnosis and treatment. This article is protected by copyright. All rights reserved.
Correlation between structural data from optical coherence tomography (OCT) and functional data from the visual field (VF) may be suboptimal because of poor mapping of OCT measurement locations to VF test stimuli. We tested the hypothesis that stronger structure-function correlations in the macula can be achieved with fundus-tracking perimetery, by precisely mapping OCT measurements to VF sensitivity at the same location. The conventional 64 superpixel (3°x3°) OCT grid was mapped to VF sensitivities averaged in 40 corresponding VF units with standard automated perimetry (conventional mapped approach, CMA) in 38 glaucoma patients and 10 healthy subjects. Similarly, a 144 superpixel (2°x2°) OCT grid was mapped to each of the 68 VF locations with fundus-tracking perimetry (localized mapped approach, LMA). For each approach, the correlation between sensitivity at each VF unit and OCT superpixel was computed and the maximum value used to generate vector maps. CMA yielded significantly higher structure-function correlations compared to LMA. Only 20% of the vectors with CMA and <5% with LMA were within corresponding mapped OCT superpixels, while most were directed towards loci with structural damage. Measurement variability and patterns of glaucomatous damage are more likely to affect the correlations rather than precise mapping of VF stimuli.
Purpose
To characterize the change of ganglion cell complex (GCC) thickness and macula vessel density in eyes diagnosed as being glaucoma suspect eyes with ocular hypertension (OHT) or glaucomatous optic neuropathy (GON).
Design
Prospective, longitudinal study.
Participants
83 eyes (24 healthy eyes, 30 OHT eyes, and 29 GON eyes) of 65 subjects who had at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was at least 3 years.
Methods
Optical coherence tomography angiography (OCTA)-based vessel density and OCT-based structural thickness of the 3×3 mm² GCC scan slab were evaluated at each visit. The rates of vessel density and thickness change were compared across diagnostic groups using linear mixed-effects model.
Main Outcome Measures
Change rates of macula GCC thickness and superficial macula vessel density.
Results
Significant mean rates of both GCC thinning and macula vessel density loss were detectable in OHT and GON groups. 49.1% of the individual suspect eyes showed significant loss (P<0.05) either with vessel density or GCC thickness. Of the GON eyes, 51.7% showed only significant GCC loss, while 17.2% showed only significant vessel density loss. Both significant GCC loss and vessel density loss was detectable in 31.0% of the GON eyes. Vessel density loss was faster than GCC thinning in half of the suspect eyes based on percent loss analysis. The age and scan quality adjusted GCC thinning rates of the OHT group (-0.59 μm/year, P=0.025) and GON group (-0.79 μm/year, P=0.058) were faster than healthy group (-0.11 μm/year), while the rate of vessel density loss was not significantly different among the diagnostic groups (all P>0.2). Higher mean intraocular pressure during follow-up was associated with a faster rate of GCC thinning in the OHT group (P=0.065) and GON groups (P=0.015), but was not associated with the rate of vessel density decrease.
Conclusions
While the rate of GCC thinning was faster on average in suspect eyes than in healthy eyes, some suspect eyes had significant loss of vessel density and faster vessel density loss than GCC thinning. OCT and OCTA are complementary and useful for evaluating eyes with OHT or GON.
Early detection and monitoring are critical to the diagnosis and management of glaucoma, a progressive optic neuropathy that causes irreversible blindness. Optical coherence tomography (OCT) has become a commonly utilized imaging modality that aids in the detection and monitoring of structural glaucomatous damage. Since its inception in 1991, OCT has progressed through multiple iterations, from time-domain OCT, to spectral-domain OCT, to swept-source OCT, all of which have progressively improved the resolution and speed of scans. Even newer technological advancements and OCT applications, such as adaptive optics, visible-light OCT, and OCT-angiography, have enriched the use of OCT in the evaluation of glaucoma. This article reviews current commercial and state-of-the-art OCT technologies and analytic techniques in the context of their utility for glaucoma diagnosis and management, as well as promising future directions.
Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Myopia is an important risk factor for glaucoma. The prevalence of myopia is increasing dramatically, and thus too, myopic glaucoma will be more often encountered. Recent advances in Spectral-Domain Optical Coherence Tomography (SD-OCT) technology enable fast, objective, and quantitative structural imaging of the optic nerve head (ONH), retinal nerve fiber layer (RNFL), and macula for facilitated and enhanced glaucoma diagnostics. However, myopic eyes have unique structural features, which might cause artifacts in OCT imaging or induce false positivity or negativity in interpreting OCT results. For correct diagnosis of glaucoma, it is essential to understand myopic eyes’ structural features that might affect imaging and interpretation of OCT. The key OCT parameters in glaucoma diagnosis include peripapillary RNFL thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and neuroretinal rim thickness measurements. Here, I review the anatomical features of these structures in myopia, how they affect imaging and the diagnostic performance of OCT, how these structures and tests might be misinterpreted, and how to overcome pitfalls and to make correct diagnoses of myopic eyes with or without glaucoma.
Purpose:
The aim of this study was to evaluate the diagnostic ability of optic nerve head (ONH), RNFL, and GC-IPL parameters in differentiating eyes with PPG from normals.
Methods:
This was a retrospective, cross-sectional, observational study. We studied 73 eyes of 41 patients and compared them to 65 eyes of 34 normal persons. Each patient underwent detailed ocular examination, standard automated perimetry, GC-IPL, ONH, and RNFL analysis. PPG was defined as eyes with normal visual field results and one or more localized RNFL defects that were associated with a glaucomatous disc appearance (e.g., notching or thinning of neuroretinal rim) and IOP more than 21 mm Hg. Diagnostic abilities of GC-IPL, ONH, and RNFL parameters were computed using area under receiver-operating curve (AUROC), sensitivity and specificity, and likelihood ratios (LRs).
Results:
All GC-IPL parameters differed significantly from normal. The ONH, RNFL, and GC-IPL parameters with best area under curves (AUCs) to differentiate PPG were vertical cup to disc ratio (0.76), inferior quadrant RNFL thickness (0.79), and inferotemporal quadrant GC-IPL thickness (0.73), respectively. Similarly, best LRs were found for clock hour 5, 6, and 12 thicknesses among RNFL; inferior sector and inferotemporal sector thicknesses among GC-IPL parameters.
Conclusion:
Diagnostic abilities of GC-IPL parameters were comparable to RNFL parameters in differentiating PPG patients from normals. The likelihood of ruling in a disease was greater with GC-IPL parameters.
Precis:
Using standard glaucoma structural and functional tests, clinicians accurately predicted the presence/absence of 10-2 glaucomatous visual field (VF) loss in 90% of the eyes in this study.
Purpose:
To investigate how well clinicians with variable experience can predict the presence and location of 10-2 VF loss using structural and functional data that are routinely obtained for glaucoma assessment.
Methods:
Within a test set of 416 eyes (210 subjects) who were diagnosed glaucoma suspect or primary open-angle glaucoma (with most eyes having mild disease), 6 clinicians were asked to predict the presence and hemispheric location of 10-2 VF loss using 24-2 VF and spectral-domain optical coherence tomography structural data. Prediction accuracies were calculated for each clinician and compared using the weighted κ-statistic. Receiver operating characteristic analyses were used to evaluate models for predicting 10-2 VF loss.
Results:
Among the 6 clinicians, mean (range) accuracy, false negatives, and false positives for predicting presence/absence of 10-2 VF loss were 90% (87% to 92%), 4.7% (2.4% to 7.0%), and 5.4% (1.7% to 7.5%) respectively. The mean (range) weighted κ-statistic was 0.75 (0.64 to 0.83), suggesting good or very good inter-rater agreement between examiners. Mean accuracy for correctly predicting hemispheric location was 73% (range, 65% to 82%) with the most common error occurring in eyes with both superior and inferior 10-2 VF defects in which one hemisphere was correctly identified but the other missed.
Conclusions:
In this study, the presence/absence of 10-2 glaucomatous VF loss was highly predictable using standard functional and structural clinical metrics. These findings suggest that 10-2 VF testing is not needed to reliably recognize and confirm central VF involvement in most eyes with glaucoma. Whether error related to identifying second hemisphere involvement in 10-2 VF loss is important requires further study.
Purpose:
Quantify the spatial error in mapping perimetric stimuli for structure-function analysis resulting from the choice of mapping scheme and eye movements.
Methods:
We analyzed data from 17 healthy and 30 glaucomatous participants. Structural data of the macula were collected with a spectral-domain optical coherence tomography. We extracted eye movement data and projection locations from a fundus tracking perimeter and quantified the retinal location mapping error (distance between the actual and the intended stimulus location in degrees from the fovea) for non-tracked perimetry in a 10-2 grid. First, we evaluated whether rotating the 10-2 grid to match the fovea-disc axis improved mapping accuracy. Second, we analyzed the effect of eccentric fixation, random eye movements, and gaze attraction from seen stimuli on projection accuracy and spread of fixation, measured with the 95% bivariate contour ellipse area (95% BCEA). We used generalized linear mixed models for our statistical analyses.
Results:
Rotating the 10-2 grid to match the fovea-disc axis significantly increased the mapping error (P < 0.001). Eye movements evoked by seen stimuli significantly increased the projection error during the test (P < 0.001). Removing such eye movements significantly reduced the 95% BCEA (P < 0.001). Eccentric fixation also significantly contributed to the projection error (P < 0.001), and its effect was larger in glaucoma patients (P < 0.001).
Conclusions:
Rotating the perimetric grid to match the fovea-disc axis is not recommended. Fixation eccentricity and instability should be taken into account for structure-function analyses.
Translational relevance:
Accounting for fixation can improve structure-function mapping in glaucoma.
Purpose
To evaluate the thinning of circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) in primary open angle glaucoma (POAG) eyes with and without history of disc hemorrhage (DH).
Design
Observational cohort study
Subjects
39 eyes (34 subjects) with DH and 117 eyes (104 subjects) without DH from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Decent and Glaucoma Evaluation Study (ADAGES).
Methods
All participants had at least 1.5-years of follow-up with a minimum of 3 visits with bi-annual spectral-domain optic coherence tomography (SD-OCT) cpRNFL and mGCIPL thickness measurements and visual fields (VF). The rates of cpRNFL and mGCIPL thinning were calculated using mixed effects models. The dynamic range-based normalized rates of cpRNFL and mGCIPL were calculated and compared between the DH and non-DH groups.
Main Outcome Measures
Rates of cpRNFL and mGCIPL thinning
Results
The rate of mGCIPL thinning was significantly faster in the DH group compared to the non-DH group (-0.62 vs. -0.38 μm/year, P=0.024). The rate of cpRNFL thinning in the DH quadrant and rate of mGCIPL thinning in inferotemporal sector in the DH group were faster than the corresponding regions in the non-DH group after adjusting for intraocular pressure (IOP) and race (-1.33 vs. -0.58 μm/year, P=0.053, and (-0.82 vs. -0.44 μm/year, P = 0.048, respectively). In the DH group, the percent rate of loss was significantly faster with mGCIPL than cpRNFL (-1.59 vs. -1.31 %/year, P=0.046). mGCIPL thinning rates were weakly associated with MD slope, VFI slope, and GPA (R² = 3.6%(P=0.058), R²=2.4%(P=0.096), and R²= 5.2%(P=0.073), respectively). The area under operating receiver curves for VF progression based on Guided Progression Analysis was 0.75 for mGCIPL and 0.56 for cpRNFL in the DH group.
Conclusions
In our study, the rate of mGCIPL and cpRNFL thinning was faster in DH eyes than non-DH eyes. mGCIPL showed higher proportional rates of thinning and greater association with functional progression compared to cpRNFL. In addition to cpRNFL, clinicians should consider incorporating mGCIPL imaging to monitor glaucoma progression, especially in glaucoma eyes with DH.
Background: Glaucoma is the leading cause of irreversible blindness worldwide. It is very important to diagnose glaucoma in early stages so that timely management can be done. Spectral domain optical coherence tomography (SD-OCT), is a newer device which helps to diagnose glaucoma early. The aim of our study was to evaluate the RNFL, ONH, and mGCA (GCL+IPL) measurements for early glaucoma detection using spectral domain optical coherence tomography (SD-OCT).Methods: Total 30, POAG (primary open angle glaucoma) suspects were compared with 30 normal controls. The Cirrus HD-OCT optic disc cube 200 × 200 protocol was used to measure ONH, RNFL and macular parameters.Results: The average cpRNFL thickness of all quadrants was significantly lower in POAG suspects, (84.13±7.42 μm versus 103.85±8.95 μm, p<0.001). The superior GCL+IPL thickness of POAG suspects and controls was 75.75±2.60 μm and 80.05±1.74 μm, respectively, (p<0.001). The inferior GCL+IPL thickness of POAG suspects and controls was 75.98±2.59 μm and 80.00±1.79 μm, respectively, (p<0.001).Conclusions: The SD-OCT is an important device to diagnose POAG suspects, early. The GCA measurements and average RNFL (especially superior and inferior) measurements, both are equally good to discriminate between glaucoma suspects and normal controls.
Transcatheter aortic valve replacement (TAVR) is associated with clinically significant cerebral microembolism and cognitive status changes. There are no data on the impact of TAVR on retinal layers. We assessed the influence of TAVR on the retinal nerve fiber layer, ganglion cell complex (GCC), and macular thickness (MT) measured by spectral domain optical coherence tomography (SD-OCT). Elderly patients (n = 50) with severe aortic stenosis undergoing TAVR were included in this study (mean age: 78.5 ± 6.9 years). Retinal nerve fiber layer, GCC, and MT were measured with SD-OCT by an ophthalmologist before and on the first day and in the first month after TAVR. The average MT was significantly increased on the first day after TAVR compared with the basal value ( P = .04). Ganglion cell complex thickness was significantly thinner on the first day after TAVR than the basal value in the inner inferior quadrant and outer temporal quadrant of the left eye ( P = .03 and .04, respectively). Postoperative changes observed on the first day compared with the preoperative period returned to basal values in the first month. In conclusion, TAVR did not cause permanent changes in retinal layers.
PRéCIS:: Based on 6 functional subzones of peripapillary retinal nerve fiber layer (pRNFL) thickness, the glaucoma detection ability of zone 2 and zone 4 was high and comparable with that of mean pRNFL in glaucoma groups.
Purpose:
To compare diagnostic performance of peripapillary retinal nerve fiber layer (pRNFL) subzones, mean pRNFL thickness and macular ganglion cell-inner plexiform layer (mGCIPL) in mild, moderate and severe open-angle glaucoma.
Methods:
181 patients with open-angle glaucoma (318 eyes: 122 mild, 60 moderate and 136 severe glaucoma) and 70 normal subjects underwent spectral-domain optical coherence tomography (SD-OCT) measurements. FORUM software was used to determine subzone pRNFL thickness mapping the visual field to the optic disc (6 zones). The thickness and area under the receiver operating curve (AUROC) of each parameter was compared between groups. DeLong's method was used to compare AUROCs between mean pRNFL and mGCIPL and each zone of SD-OCT parameters.
Results:
Mean pRNFL thickness (99.81±10.06▒μm) and mGCIPL thickness (83.24±5.91▒μm) were higher in controls compared to glaucoma (67.42±13.22▒μm and 63.31±10.85▒μm; P<0.001).Mean pRNFL had the best diagnostic performance in mild (0.957) and severe (1.000) glaucoma. Of the 6 zonal parameters, zone 2 (associated with the inferior temporal sector) best discriminated glaucomatous changes between controls and mild and moderate (0.941 and 0.988). Zone 4 (associated with the superior temporal sector) best discriminated glaucomatous changes between controls and severe glaucoma (0.998). AUROCs for zone 2 and zone 4 were not significantly different from mean pRNFL and mGCIPL in all glaucoma groups (all P>0.0038).
Conclusions:
Mean pRNFL had the best diagnostic performance in mild and severe glaucoma. Glaucoma detection ability of zone 2 and zone 4 was high and comparable with that of mean pRNFL and mGCIPL in all glaucoma groups.
PRéCIS:: In the adult offspring of glaucoma patients, RNFL and GCC thickness in the especially inferior quadrant were significantly decreased. This finding in the adult offspring of glaucoma patients may be important in evaluating the course of glaucoma disease.
Purpose:
The aim of this study is to investigate retinal nerve fiber layer and ganglion cell complex thickness in adult offspring of primer open angle glaucoma patients and to compare the results with individuals without a family history for glaucoma disease.
Materials and methods:
This was a cross-sectional observational study. Forty eyes of 40 individuals with self reported family history for proven primary open-angle glaucoma (POAG) and forty eyes of 40 healthy individuals without a family history for glaucoma disease were included in the study. Retinal nerve fiber layer (RNFL) and macular ganglion cell complex(GCC) thickness were measured by spectral domain optical coherence tomography (OCT), and the results were compared between the two groups.
Results:
In adult offspring of patients with POAG, RNFL and GCC thickness were thinner in all quadrants. Average RNFL and GCC decreased significantly in adult offspring of patients with POAG (P=0.039, P=0.015, respectively). Thinning in RNFL and GCC thickness was especially significant in the inferior quadrant (P=0.024, P=0.039, respectively). There is no significant difference between the groups in terms of MD and PSD values (P=0.064, P=0.091, respectively).
Conclusion:
In adult offspring of POAG patients, especially in the inferior quadrant, the retinal nerve fiber layer and ganglion cell complex thicknesses are significantly lower than subjects without a family history. Prospective, controlled clinical trials with longer follow-up are needed to better understand whether these changes are an early indicator of glaucoma, and the progression of glaucoma disease.
Structural designing of carriers with extended drug release profiles is critically important for achieving long-acting drug delivery systems toward efficient managements of chronic diseases. Here, we present a strategy to exploit the effects of the shell thickness of hollow poly(lactic acid) nanoparticles (HPLA NPs) in sustained glaucoma therapy. Formulations based on pilocarpine-loaded HPLA NPs with tailorable shell thickness ranging from 10 to 100 nm were shown to be highly compatible with human lens epithelial cells in vitro and with rabbit eyes in vivo. Specifically, shell thickness regulated the release of pilocarpine, with thick shells (~70 to 100 nm) providing sustained drug release performance but limited drug-loading efficiency, whereas ultrathin shells (~10 nm) induced the opposite effects. Remarkably, moderately thick shells (~40 nm) showed the most effective release profile of pilocarpine (above the therapeutic levels of ~10 µg/mL for over 56 days). In a rabbit model of glaucoma, single intracameral administration of an HPLA NP-based formulation with shell thickness of ~40 nm sustainably alleviated ocular hypertension for over 56 days, consequently protecting the structural integrity of the corneal endothelium, preserving the electrophysiological functions of the retina, and attenuating retinal and optic nerve degeneration in progressively glaucomatous eyes. The findings therefore implied a promising use of shell thickness effects in the development of long-acting drug delivery systems for pharmacological treatment of chronic ocular diseases.
Statement of Significance
Owing to their large surface areas and modifiable structures, nanoparticles have been considered as a promising platform for drug delivery; however, achieving drug nanocarrier systems with reduced burst release and sustained therapeutic efficacy remains challenges. This work presents the first report on rational design of hollow poly(lactic acid) nanocarriers for tailoring the structure-property-function relationships toward effective treatment of glaucoma. The shell thickness of the hollow nanocarriers is demonstrated to have influential impacts on pilocarpine encapsulation efficiency and release profile, indicating that the most sustained delivery performance (maintaining the release of pilocarpine above therapeutic level over 56 days) can be obtained for the polymeric nanoparticles with moderate shell thickness of ~40 nm.
Purpose
To evaluate the capacity of retinal nerve fibre layer (RNFL) thickness measured by SD‐OCT to discriminate glaucoma patients from controls in an elderly population.
Methods
The MONTRACHET (Maculopathy, Optic Nerve, nuTRition, neurovAsCular and HEarT diseases) Study is a population‐based study including participants aged 75 years and over. All participants underwent a complete eye examination with optic nerve photographs, visual field testing and OCT peripapillary RNFL thickness measurement. Glaucoma was defined according to the ISGEO (International Society for Epidemiologic and Geographical Ophthalmology) classification. Performance indicators were calculated including area under the receiver operating characteristics curves (AUC), likelihood ratios (LR) and diagnostic odds ratios (DOR).
Results
In total, 1061 participants were included in the study, of whom 89 were classified as having glaucoma and 972 were classified as normal. The mean (SD) age of the population was 82.3 (3.7) years. The average RNFL thickness was significantly lower in the glaucoma group than in controls 64.0 (14.9) µm versus 88.9 (12.4) µm, respectively, p < 0.001) and in all sectors compared with controls. The average RNFL thickness had the highest AUC (0.901) followed by the temporal‐inferior (0.879) and temporal‐superior sectors (0.862). When RNFL thickness was classified as abnormal by SD‐OCT, the average RNFL thickness had the best sensitivity (83.75%) followed by the temporal‐inferior sector (75.64%). The specificity for these two parameters was 87.34% and 91.08%, respectively. The highest DOR was 28.70 for average RNFL thickness and reached 34.84 when using the reference database of the OCT manufacturer.
Conclusion
This study confirms that SD‐OCT could be useful as an additional test to discriminate glaucoma patients from controls in an elderly population.
We quantified the spatial distribution of presumed ganglion cells and displaced amacrine cells in unstained whole mounts of six young normal human retinas whose photoreceptor distributions had previously been characterized. Cells with large somata compared to their nuclei were considered ganglion cells; cells with small somata relative to their nuclei were considered displaced amacrine cells. Within the central area, ganglion cell densities reach 32,000--38,000 cells/mm² in a horizontally oriented elliptical ring 0.4--2.0 mm from the foveal center. In peripheral retina, densities in nasal retina exceed those at corresponding eccentricities in temporal retina by more than 300%; superior exceeds inferior by 60%. Displaced amacrine cells represented 3% of the total cells in central retina and nearly 80% in the far periphery. A twofold range in the total number of ganglion cells (0.7 to 1.5 million) was largely explained by a similar range in ganglion cell density in different eyes. Cone and ganglion cell number were not correlated, and the overall cone: ganglion cell ratio ranged from 2.9 to 7.5 in different eyes. Peripheral cones and ganglion cells have different topographies, thus suggesting meridianal differences in convergence onto individual ganglion cells.
There are many devastating ocular diseases that are directly related to an alteration of the retinal or nerve fiber layer thickness, such as glaucoma and macular edema. To diagnose these diseases earlier and to monitor their therapy more sensitively, an accurate measurement of the tissue thickness is needed. Since no clinical method is currently available, we developed and tested a new method capable of measuring noninvasively the retinal thickness. The separation between the images of the anterior and posterior intersections is quantitated by an optoelectronic system. The theoretical performance of the method has been calculated. Tests of the method in a model eye indicated that the measurements were basically diffraction limited, their reproductivity was +/- 9 microns, and their accuracy was 5.5 microns. Tests performed in vivo indicated that two intersections between the laser and the retina are present and correspond to the anterior and posterior surfaces of the retina. These intersections can be resolved and analyzed to yield quantitative data. These encouraging results indicate that this method is feasible and could yield sensitive measurements of the retinal thickness.
To determine if photoreceptors die in primary open-angle glaucoma.
Retinas were examined in a masked fashion from nine standard locations of 14 eyes with documented open-angle glaucoma and from nine age-matched control eyes. The number and density of photoreceptors, as well as the area and height of the outer nuclear layer, were calculated with an automated image analysis system. The number of photoreceptors per 0.1 mm of retina was determined.
No significant difference was seen between control and glaucomatous eyes in comparisons of photoreceptor density, outer nuclear layer height, or photoreceptors per 0.1 mm of retinal length in nine retinal zones. There was no detectable association between photoreceptor number and severity of glaucoma (defined as mild, moderate, or severe), visual field, and optic nerve fiber loss. In eyes in which damage predominated in the upper or lower visual field, no corresponding difference in photoreceptor number in upper compared to lower retinal zones was observed.
Photoreceptors are not lost in substantial numbers in primary open-angle glaucoma.
The purpose of this study was to study the pattern of foveal ganglion cell loss in experimental glaucoma.
Retinal ganglion cell size and number in the foveal region of seven monkey eyes with experimental glaucoma was determined and compared to normal monkey eyes. Serial sections of macular retina were studied in two regions: the plateau of peak density of ganglion cells (800-1100 microns from the fovea), and within 500 microns of the foveal center.
In normal eyes, cell densities were 37,900 +/- 2700 in the foveal plateau and 17,200 +/- 1800 cells/mm2 in the foveal center. There was selective loss of larger ganglion cells in glaucoma eyes. The degree of foveal ganglion cell loss was significantly correlated to the degree of nerve fiber loss in the temporal optic nerve of the same eye.
Detection of early, central visual function loss in glaucoma could be enhanced by testing functions subserved by larger retinal ganglion cells.
• Diabetic macular edema is a major cause of vision loss and is evaluated with qualitative or semiquantitative techniques. A new quantitative method for assessment of macular edema using retinal thickness analysis was applied to 19 patients with diabetic macular edema. Foveal thickening was frequently coupled with poor visual acuity. Slit-lamp biomicroscopy and stereophotography detected 80% and 78% of local areas of thickening, respectively, but failed to detect locations with average thicknesses of 1.5 and 1.6 times normal, respectively. Fluorescein leakage on angiography was generally associated with retinal thickening, but locations with similar degrees of leakage had widely varying retinal thickening. Fluorescein leakage in the posterior vitreous correlated poorly with the degree of foveal thickening. These results indicate that quantitative measurement of retinal thickness may become useful in the management of diabetic patients with macular edema.
Objective:
To determine race-, age-, gender-, and refractive error—related differences in the size and topography of the optic disc in healthy Americans.
Design:
Population-based study.
Setting:
Eastern and southeastern health districts of Baltimore, Md.
Participants:
A population-based sample of 4877 noninstitutionalized black and white individuals aged 40 years or older without evidence of optic nerve disease.
Main Outcome Measure:
Race-, age-, gender-, and refractive error—related differences in optic disc measurements: disc area, neural rim area, cup area, cup-to-disc ratio, and neural rim area—to—disc area ratio.
Results:
We analyzed simultaneous stereoscopic optic disc photographs from 3387 (1534 black and 1853 white) of the 4877 healthy individuals using an image analyzer (Topcon Image Analyzer, Topcon Instrument Corporation, Paramus, NJ). A total of 1490 individuals were excluded owing to the absence of good-quality images from either eye. The image analyzer defined the cup margin 150 μm below the surface of the disc margin. On average, blacks had significantly larger disc areas (blacks, 2.94 mm2; whites, 2.63 mm2), larger cup areas (blacks, 1.04 mm2; whites, 0.71 mm2), larger cup-to-disc ratios (blacks, 0.56; whites, 0.49), similar neural rim areas (blacks, 1.90 mm2; whites, 1.92 mm2), and smaller neural rim area-to—disc area ratios (blacks, 0.66; whites, 0.74) compared with whites. There were no age-related differences in any of the disc measurements. Male subjects had 2% to 3% larger optic discs compared with female subjects. No association between refractive error and any of the optic disc mesurements studied was detected.
Conclusions:
Racial differences in the normal optic disc are present among urban Americans, and these differences must be considered in evaluation of the optic disc for glaucoma and other optic neuropathies. Among the individuals in our study, all of whom were 40 years of age or older, no progressive age-related decline in neural rim area was detectable. Neither gender nor refractive error were associated with any significant differences in the size and topography of the normal optic disc.
Purpose:
Quantitative assessment of nerve fiber layer (NFL) thickness in normal and glaucomatous eyes, and correlation with conventional measurements of the optic nerve structure and function.
Methods:
We studied 59 eyes of 33 subjects by conventional ophthalmologic physical examination, Humphrey 24-2 visual fields, stereoscopic optic nerve head photography, and optical coherence tomography.
Results:
Nerve fiber layer thickness as measured by optical coherence tomography demonstrated a high degree of correlation with functional status of the optic nerve, as measured by visual field examination (P=.0001). Neither cupping of the optic nerve nor neuroretinal rim area were as strongly associated with visual field loss as was NFL thickness (P=.17 and P=.21,respectively). Cupping correlated with NFL thickness only when the cup was small (cup-to-diameter ratio, 0.1 to 0.3) or large (cup-to-diameter ratio, 0.8 to 1.0) (P=.006); there was no correlation between cupping and NFL thickness otherwise. Nerve fiber layer, especially in the inferior quadrant, was significantly thinner in glaucomatous eyes than in normal eyes (P=.04). Finally, we found a decrease in NFL thickness with aging, even when controlling for factors associated with the diagnosis of glaucoma (P=.03).
Conclusions:
Nerve fiber layer thickness can be measured using optical coherence tomography. These measurements provide good structural and functional correlation with known parameters.
In order to diagnose certain ocular diseases such as macular edema and atrophy, and to monitor their therapy closely, an accurate measurement of the retinal thickness is essential. We have developed a method which is capable of providing a quantitative thickness profile along a 2 mm length on the retina. A preliminary evaluation of the instrument was performed in normal human subjects. With this method, the retinal thickness can be visualized in a region extending from the optic disc to the fovea and the reproducibility of the measurement was found to be 8% (32 microns).
The magnification of the Zeiss type of fundus camera depends, except for the case of emmetropy, on the camera-to-eye distance. Its relative variation is equal to the product of the patient's ametropia and the difference in the camera-to-eye distance. Moreover, magnification is also affected by changing the diopter range scales on the camera.
We have examined by light and electron microscopy the retina, optic nervehead, and optic nerves of 21 human eyes from glaucoma patients in whom clinical information was available for comparison. In several cases it was possible to correlate the degree and distribution of optic nerve damage with the clinical appearance of the optic disc and visual field studies. There was no selective loss of astrocytes of the optic nervehead in early glaucoma cupping. Acquired increases in optic disc cup size prior to detectable visual field loss probably represent loss of ganglion cell axonal fibers which is not yet significant enough to produce field defects. It is unlikely that the mechanism of axonal damage in chronic human glaucoma involves early loss of astrocytic glial cells at the optic nervehead. At the level of the retrobulbar optic nerve, the ganglion cell axonal fibers of the superior and inferior quadrants seem to be lost earlier than the fibers of the nasal and temporal nerve periphery. Since the superior and inferior poles of the optic nerve may contain the fibers of arcuate area ganglion cells, these data confirm the presumption from visual field testing that arcuate area ganglion cell fibers are selectively more susceptible to damage in chronic glaucoma.
Diabetic macular edema is a major cause of vision loss and is evaluated with qualitative or semiquantitative techniques. A new quantitative method for assessment of macular edema using retinal thickness analysis was applied to 19 patients with diabetic macular edema. Foveal thickening was frequently coupled with poor visual acuity. Slit-lamp biomicroscopy and stereophotography detected 80% and 78% of local areas of thickening, respectively, but failed to detect locations with average thicknesses of 1.5 and 1.6 times normal, respectively. Fluorescein leakage on angiography was generally associated with retinal thickening, but locations with similar degrees of leakage had widely varying retinal thickening. Fluorescein leakage in the posterior vitreous correlated poorly with the degree of foveal thickening. These results indicate that quantitative measurement of retinal thickness may become useful in the management of diabetic patients with macular edema.
A noninvasive method has been developed that is capable of providing quantitative thickness profiles of the retina. The method was used to map the retinal thickness in five normal human volunteers and determine the reproducibility of the measurements. The reproducibility or equivalent sensitivity of the measurements to detect changes was found to be 5% or 19 microns on the same day and 8% or 31 microns on different days. By averaging the values obtained in five normal subjects, ranging in age from 21 to 43 years (mean, 34 years), a preliminary normal baseline was derived for the thickness profile at the fovea and the thickness cross-section from the optic disc to the fovea. The results of the study indicated that this noninvasive method promises to be of clinical use in diagnosing ocular diseases that produce changes in the thickness of the retinal as well as in monitoring the effectiveness of therapy.
We studied the size, shape, and configuration of connective tissue of the optic disc in normal eye-bank eyes from 60 adults. The mean vertical and horizontal disc diameters were 1.88 and 1.77 mm, respectively. These figures are larger than most estimates of disc diameter using clinical image analysis methods. Within our sample, larger eyes did not have larger discs. The normal variation in disc diameter is sufficient to explain the normal variation in cup-disc ratio. The optic discs of blacks were larger and more oval than those of whites, though the axial lengths of the eyes in the two groups were not significantly different. Women's eyes and discs were smaller than those of men, possibly explaining the smaller cup-disc ratio in women. Larger optic discs and optic nerves have more optic nerve fibers than do smaller discs and nerves. Oblique insertions of the disc were detected in 18% of eyes. These were predominantly centered in the inferior disc and were more commin in white women.
Reliable structural markers for early glaucomatous optic nerve damage would facilitate the diagnosis of glaucoma at an early stage, possibly before visual field loss occurs. Computerized image analyses were used to develop and analyze new structural parameters for glaucomatous optic nerve damage. Multiple measurements of relative juxtapapillary nerve fiber layer height were made in glaucoma patients (n = 112), patients suspected of having glaucoma (n = 87), and in age-matched normal control subjects (n = 53). The average relative nerve fiber layer (NFL) height differed in glaucoma patients and normal subjects by 70 microns, but differences exceeded 100 microns at the superior and inferior poles of the disc. Mean values for "glaucoma suspects" were intermediate between those for the normal subjects and glaucoma groups. The ability of summary statistics of relative NFL height measurements to discriminate between normal and glaucomatous eyes was superior to that of the standard disc parameters cup-disc ratio, disc rim area, and cup volume. Measurements of relative NFL height correlated with indices of visual field loss; the strongest correlations occurred for measurements at the superior and inferior poles. Measurements of juxtapapillary NFL height may prove useful to detect glaucomatous optic nerve damage at an early stage and to accurately recognize progressive nerve damage over time.
We measured the number and size of retinal ganglion cells from six human eyes with glaucoma. In each, the histologic findings were correlated with visual field results. Five age-matched normal eyes were studied for comparison. In general, there were fewer remaining large ganglion cells in retinal areas with atrophy. In the perifoveal area, however, no consistent pattern of cell loss by size was found. Our estimates suggest that visual field sensitivity in automated testing begins to decline soon after the initial loss of ganglion cells. Throughout the central 30 degrees of the retina, 20% of the normal number of cells were gone in locations with a 5-dB sensitivity loss, and 40% cell loss corresponded to a 10-dB decrease. There were some remaining ganglion cells in areas that had 0-dB sensitivity in the field test.
Topographic analysis and measurement of the optic nerve head is important for the diagnosis and follow-up of glaucoma. To quantify structures of the optic nerve head the new technique of laser tomographic scanning was used. A laser beam was focused onto the surface of the optic nerve head and the reflected light was detected in a confocal detection unit. The consequent change of focus produced a tomographic scanning series and allowed measurement of three-dimensional structures. To analyze the reproducibility of optic cup measurements the authors did ten recordings of one eye of eight normal volunteers. The mean standard deviation of the measurements was +/- 0.015 mm3 and the mean coefficient of variation was 9.5%. Confocal laser tomographic scanning is a safe, effective, convenient method to measure and document the topography of the optic nerve head and should be a valuable technique for follow-up of glaucoma patients.
In one optic nerve from each of 19 persons, the authors determined the number of axons, the distribution of fiber diameter, and the total neural area. The mean fiber count was 693,316, the mean neural area was 5.17 mm2, and the mean axonal fiber diameter was 0.96 microns. No significant decline in fiber number or neural area with increasing age was found. The authors found a large variability of axonal number among their patients. This variability would have obscured any small effect of aging. Linear regression analysis of the effect of age on mean axonal diameter yielded a slight negative slope (P less than 0.01), suggesting a redistribution of fiber diameter. This could occur from axonal shrinkage, from preferential large fiber loss, or from the technical features of tissue acquisition and analysis. The authors suspect that the explanation is a selective loss of large nerve fibers.
Topographic measurements of the optic nerve head were made with computerized videographic image analysis (Rodenstock Analyzer) in one eye each of 36 normal controls, 41 glaucoma suspects and 46 glaucoma patients matched for age. Glaucoma suspects had elevated intraocular pressures and normal visual fields in both eyes. Glaucoma patients had typical visual field defects. Disc measurements were corrected for the optical dimensions of individual eyes. One-way analysis of variance revealed statistically significant differences among the diagnostic groups for cup-disc ratio (P = 0.0006), disc rim area (P less than 0.0001) and cup volume (P = 0.0001). Mean (+/- SEM) disc rim area was 1.14 +/- 0.04 mm2 for controls, 1.10 +/- 0.04 mm2 for glaucoma suspects and 0.87 +/- 0.05 mm2 for glaucoma patients. Mean (+/- SEM) optic nerve cup volume was 0.35 +/- 0.02 mm3 for controls, 0.44 +/- 0.04 mm3 for glaucoma suspects and 0.60 +/- 0.05 mm3 for glaucoma patients. Planimetric measurements of disc rim area were made from manual tracings of stereoscopic disc photographs of the same eyes. There was a statistically significant correlation between the computerized videographic measurements and the manual photographic measurements of disc rim area (r = 0.73, P less than 0.0001). The broad range of values for these optic nerve structural parameters in normal eyes and their overlap with values in glaucomatous eyes prevents their use to reliably predict which patients are normal and which have glaucomatous visual field loss. New parameters are required to fully describe the depth information generated with new quantitative techniques.
The number and distribution of human optic nerve axons were compared with clinical measurements available the same eyes, including visual acuity, disc appearance, and visual field studies. Definite loss of axons occurs prior to reproducible visual field defects in some patients suspected of having glaucoma. In glaucoma, the superior and inferior poles of the nerve lose nerve fibers at a selectively greater rate, leading to an hourglass-shaped atrophy. Cavernous degeneration of the retrobulbar optic nerve is rarely observed in chronic glaucoma. The pattern of atrophy in examples of toxic amblyopia, ischemic optic neuropathy and chronic papilledema differ from that of glaucoma, suggesting different mechanisms of damage in these conditions.
To determine whether retardation (change in polarization) measurements of healthy subjects and glaucoma patients obtained by using a confocal scanning laser polarimeter correspond to known properties of the nerve fiber layer.
A polarimeter, an optical device used to measure the change in linear polarization of light (retardation), was interfaced with a scanning laser ophthalmoscope to obtain retardation data at 65,536 locations (256 x 256 pixels) in a study of normal subjects and patients with primary open-angle glaucoma. To validate the instrument, we compared our measurements with known properties of the human retinal nerve fiber layer in 105 normal subjects. Additionally, we compared retardation measurements in eyes of 64 normal subjects and 64 age-matched glaucoma patients treated in a referral practice.
In normal eyes, mean (+/- S.D.) peripapillary retardation was highest in the superior and inferior arcuate regions and lowest in the temporal and nasal regions, 12.0 +/- 1.9, 13.1 +/- 2.0, 7.0 +/- 1.8, and 7.0 +/- 1.6 degrees, respectively. Retardation decreased toward the periphery and was lower over blood vessels. In normal eyes, retardation decreased with increasing age in the superior and inferior regions. Mean retardation was statistically significantly higher among normal eyes than glaucoma eyes in the inferior and superior regions but not in the temporal or nasal areas.
Scanning laser polarimetry provides quantitative measurements that correspond to known properties of the retinal nerve fiber layer in normal and glaucomatous eyes.
Quantitative assessment of nerve fiber layer (NFL) thickness in normal and glaucomatous eyes, and correlation with conventional measurements of the optic nerve structure and function.
We studied 59 eyes of 33 subjects by conventional ophthalmologic physical examination, Humphrey 24-2 visual fields, stereoscopic optic nerve head photography, and optical coherence tomography.
Nerve fiber layer thickness as measured by optical coherence tomography demonstrated a high degree of correlation with functional status of the optic nerve, as measured by visual field examination (P = .0001). Neither cupping of the optic nerve nor neuroretinal rim area were as strongly associated with visual field loss as was NFL thickness (P = .17 and P = .21, respectively). Cupping correlated with NFL thickness only when the cup was small (cup-to-diameter ratio, 0.1 to 0.3) or large (cup-to-diameter ratio, 0.8 to 1.0) (P = .006); there was no correlation between cupping and NFL thickness otherwise. Nerve fiber layer, especially in the inferior quadrant, was significantly thinner in glaucomatous eyes than in normal eyes (P = .04). Finally, we found a decrease in NFL thickness with aging, even when controlling for factors associated with the diagnosis of glaucoma (P = .03).
Nerve fiber layer thickness can be measured using optical coherence tomography. These measurements provide good structural and functional correlation with known parameters.
Using confocal scanning laser tomography, we studied the test-retest variability of topographic measurements of the optic nerve head and parapapillary retina in 30 patients with glaucoma and 30 normal control subjects. We obtained three independent images, separated by between one and six hours, centered on the optic nerve head. We condensed each original 256 x 256-pixel image to a 64 x 64-pixel image, thereby allowing a realistic estimate of the empiric 90% confidence interval of testretest variability at each condensed pixel. Confidence interval maps generated for each subject showed highest measurement variability along the cup border and blood vessels. The mean standard deviation equivalents of test-retest variability in the patients and controls were 31.20 and 25.94 microns, respectively. These differences were statistically significant (P = .010). Variability increased with age (P < .001). When the analysis was repeated for discrete parapapillary areas, the group differences were not statistically significant (P = .100).
Scanning laser ophthalmoscopy is a laser-based image acquisition technique, which greatly improves the quality of the examination of the fundus and the retinal nerve fiber layer. To assess retinal nerve fiber layer imaging by scanning laser ophthalmoscopy and evaluate intra- and interobserver reproducibility in the classification of retinal nerve fiber layer defects, three independent observers evaluated on two separate occasions the videotaped images of 150 eyes of 80 consecutive patients with ocular hypertension or glaucoma. Ophthalmoscopy was performed using argon blue light (488 nm), confocal apertures of 3 to 1 mm, and 40-degree and 20-degree field angles. Of 150 eyes, 20 (13.3%) were excluded from the study because of the poor quality of the images (clinically significant cataract or myopic peripapillary atrophy). The retinal nerve fiber layer was evaluated qualitatively according to a standard classification: normal pattern, slit, wedge, and diffuse defects. Intraobserver reproducibility, evaluated by kappa statistic, was excellent (> or = 0.75): observer A = 0.78 (95% confidence limits, 0.67-0.88); observer B = 0.84 (95% confidence limits, 0.72-0.96); and observer C = 0.79 (95% confidence limits, 0.67-0.91). Interobserver reproducibility was also excellent in all cases: observers A-B = 0.84 (95% confidence limits, 0.71-0.98); observers A-C = 0.76 (95% confidence limits, 0.65-0.87); and observers B-C = 0.80 (95% confidence limits, 0.69-0.92). Kappa values ranged between 0.59 and 0.69 for intraobserver reproducibility and between 0.55 and 0.69 for interobserver reproducibility when using only those eyes in which abnormalities were noted by at least one observer.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine race-, age-, gender-, and refractive error-related differences in the size and topography of the optic disc in healthy Americans.
Population-based study.
Eastern and southeastern health districts of Baltimore, Md.
A population-based sample of 4877 non-institutionalized black and white individuals aged 40 years or older without evidence of optic nerve disease.
Race-, age-, gender-, and refractive error-related differences in optic disc measurements: disc area, neural rim area, cup area, cup-to-disc ratio, and neural rim area-to-disc area ratio.
We analyzed simultaneous stereoscopic optic disc photographs from 3387 (1534 black and 1853 white) of the 4877 healthy individuals using an image analyzer (Topcon Image Analyzer, Topcon Instrument Corporation, Paramus, NJ). A total of 1490 individuals were excluded owing to the absence of good-quality images from either eye. The image analyzer defined the cup margin 150 microns below the surface of the disc margin. On average, blacks had significantly larger disc areas (blacks, 2.94 mm2; whites, 2.63 mm2), larger cup areas (blacks, 1.04 mm2; whites, 0.71 mm2), larger cup-to-disc ratios (blacks, 0.56; whites, 0.49), similar neural rim areas (blacks, 1.90 mm2; whites, 1.92 mm2), and smaller neural rim area-to-disc area ratios (blacks, 0.66; whites, 0.74) compared with whites. There were no age-related differences in any of the disc measurements. Male subjects had 2% to 3% larger optic discs compared with female subjects. No association between refractive error and any of the optic disc measurements studied was detected.
Racial differences in the normal optic disc are present among urban Americans, and these differences must be considered in evaluation of the optic disc for glaucoma and other optic neuropathies. Among the individuals in our study, all of whom were 40 years of age or older, no progressive age-related decline in neural rim area was detectable. Neither gender nor refractive error were associated with any significant differences in the size and topography of the normal optic disc.
This study describes the dark-adapted electroretinograms (ERGs) of macaque monkeys with severe visual field defects and substantial retinal ganglion cell loss as a consequence of long-standing ocular hypertension.
Monocular experimental glaucoma was produced by argon laser trabeculoplasty, and visual fields were assessed with behavioral static perimetry. Electroretinographic responses to brief ganzfeld flashes under fully dark-adapted conditions were recorded using DTL fiber electrodes in anesthetized animals. The authors quantified retinal layer thickness and cell loss in 1-micron radial sections and inspected optic nervous under the light microscope.
At the lowest intensities, a sensitive negative component of the scotopic ERG, which normally peaks approximately 200 msec after stimulus onset, was present in the control eyes but was reduced greatly or was virtually absent in the experimental eyes of monkeys with severe visual field loss. A previously unreported sensitive positive component of the scotopic ERG remained in both eyes. In the control eyes, the positive component gave rise to a sharp peak approximately 120 msec after stimulus onset, but in the experimental eyes, because of the absence of the more delayed sensitive negative potential, it was sustained, lasting as long as 700 msec. Scotopic a- and b-waves and oscillatory potentials in the experimental eyes were not consistently different from control eyes. Ganglion cell and optic nerve loss in the experimental eyes was substantial, and there was little other obvious retinal damage.
A sensitive negative component is reduced or absent from the dark-adapted ERGs of macaque monkeys with severe visual field defects and substantial retinal ganglion cell loss as a consequence of long-standing ocular hypertension.
To determine whether, in a clinical setting, scanning laser polarimetry and retinal nerve fiber layer photography provide equivalent information on the retinal nerve fiber layer.
We prospectively studied 60 patients with glaucoma or ocular hypertension and 24 healthy subjects. With scanning laser polarimetry, an estimate of the cross section of the retinal nerve fiber layer was obtained. By using a photographic reference set, we quantified photographs of the retinal nerve fiber layer. Visual fields were used to relate the results of both methods to functional damage.
The scanning laser polarimetry measurements yielded reproducible cross-section values (coefficient of variation, 6.6%). Comparison of cross-section values and photograph scores gave Pearson correlation coefficients smaller than r = .4 (P < .01), improving to a maximum of r = .53 after compensation for offset. When cross-section values were compared to the mean deviation of the visual field, the Spearman correlation coefficients varied from an r of -.34 to -.53 (P < .01). Correction for offset resulted in an r of -.54 to -.65. When photograph scores and mean deviation of the visual field were compared, the Spearman correlation coefficients varied from an r of -.65 to -.71 (P < .01).
Because r was maximal at .53, the information on the retinal nerve fiber layer obtained with scanning laser polarimetry and photography seems not equivalent. This result could not have been because of lack of reproducibility. Although the results suggested possible offset in scanning laser polarimetry, other methodologic differences must be considered to explain the differences between the two techniques.
An objective, quantitative, and sensitive method to map retinal thickness is needed to diagnose more effectively the conditions causing alterations in thickness, such as macular edema and neuroretinal atrophy.
An instrument, the retinal thickness analyzer, was developed into a rapid scanning instrument, capable of covering macular areas of 2 x 2 mm in 200 or 400 msec and generating a detailed map of the retinal thickness. The performance was assessed in vitro and in five normal subjects who were scanned on three separate visits.
Optimal depth precision was 5 to 10 microns, and the optimal depth resolution was 50 microns. Reproducibility was +/- 12 microns on the same day, +/- 13 microns for single maps obtained in multiple visits, and +/- 10 microns for three averaged maps per visit obtained in multiple visits.
This new method to analyze retinal thickness provides four unique features: multiple optical cross-sectioning of the retina, mapping of retinal thickness, high reproducibility, and short acquisition time. These capabilities promise to improve the diagnosis and management of common diseases such as macular edema and glaucoma.
To determine whether an association exists between migraine headache history and open-angle glaucoma (OAG).
Population-based, cross-sectional study.
Subjects were 3654 people aged 49 or older; 82% of permanent residents from an area west of Sydney participated.
All participants underwent an interview and a detailed eye examination, including automated perimetry and stereo optic disc photography.
Open-angle glaucoma was diagnosed in subjects with matching typical glaucomatous visual field defects and pathologic optic disc cupping, independent of intraocular pressure level. The diagnosis of migraine history (typical or nontypical) was based on participant responses to specific questions, consistent with International Headache Society criteria.
Open-angle glaucoma prevalence increased exponentially with age, with rates of 0.4%, 1.3%, 4.7%, and 11.4% among persons aged less than 60 years, between 60 and 69 years, between 70 and 79 years, and 80 years or older, respectively. The frequency of reporting a past history of typical migraine headache declined with increasing age, with rates of 23.1%, 16.2%, 12.8%, and 10.4% for corresponding age groups. For all age groups combined, there was no significant association between typical migraine headache and OAG (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.8-2.2), after multivariate adjustment. However, after stratifying into 10-year age groups, increased odds for OAG were found for people giving a history of typical migraine headache and aged 70-79 years (OR, 2.5; 95% CI 1.2-5.2), after adjusting for variables found associated with glaucoma. This association was marginally stronger for high-pressure OAG cases (OR, 2.7; 95% CI, 1.1-5.6).
These data suggest the possibility of an association between history of typical migraine headache and OAG, which could be modified by age.
Reproducibility of retinal nerve fiber layer evaluation by dynamic scanning ophthalmoscopy
- Miglior
The normal topographical anatomy of the retinal ganglion cell layer
- Van Buren