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Peripapillary and macular vessel density (VD) are reduced in myopic non-glaucomatous eyes, the dynamic range of VD may be decreased by myopia, and whether VD measurement has the potential in differentiating stages of glaucoma severity in patients with myopic glaucoma remains questionable. This observational, cross-sectional study aimed to clarify the changes in peripapillary and macular VDs in preperimetric glaucoma (PPG) and primary open-angle glaucoma in the early, moderate, and late stages. A total of 1228 eyes from 661 participants (540 normal, 67 PPG, and 521 glaucomatous) were included. Participants underwent free blood tests at the internal medicine clinic to retrieve systemic data. Patients with glaucoma were grouped by disease severity, defined by glaucomatous visual field mean defect, including early-(224 eyes), moderate-(103 eyes), and late-stage glaucoma (194 eyes), and further divided into advanced (158 eyes) and terminal glaucoma (36 eyes). Macular VD, peripapillary VD, circumpapillary retinal nerve fiber layer (cpRNFL) thickness, and ganglion cell complex (GCC) thickness were evaluated and divided into superior and inferior parts. One-way analysis of variance was performed, followed by Tukey’s post-hoc test. The peripapillary VD was significantly different between the healthy and PPG groups and the early-, moderate-, and late-stage glaucoma subgroups (all p < 0.001). Peripapillary VD measurements are helpful in differentiating the various stages of glaucoma even in patients with myopic glaucoma.

Purpose To investigate vessel density (VD) of radial peripapillary capillaries (RPC) and structural alterations in patients with unilateral preperimetric glaucoma (PPG) using optical coherence tomography angiography (OCTA). Methods This cross-sectional observational study included 13 untreated patients with unilateral PPG. PPG eyes had larger excavation and abnormal thinning of retinal nerve fiber layer (RNFL) and/or ganglion cell complex (GCC) compared with fellow eyes (F). Both RNFL and GCC thickness in F were statistically within normal limits and/or borderline. The RPC VD on optic disc (idVD), of peripapillary (ppVD) and whole image (wiVD) scan area was measured. Twenty healthy eyes (H) served as controls. Structural and vascular parameters obtained by spectral-domain OCT/OCTA (Optovue; Fremont, CA) were compared between PPG, F and H. Results Mean RNFL and GCC average thickness in microns differed significantly (p 0.9). AUROCs between F and H demonstrated an excellent diagnostic ability for structural parameters and a poor one (

PRECIS Macular superficial capillary plexus (SCP) vessel density is more informative than deep capillary plexus (DCP) vessel density for the detection of glaucoma. PURPOSE The purpose of this study was to characterize optical coherence tomography angiography macular SCP and projection-resolved DCP vessel densities and compare their diagnostic accuracies with ganglion cell complex (GCC) thickness in healthy, glaucoma suspect, and glaucoma eyes. MATERIALS AND METHODS Sixty-eight eyes of 44 healthy subjects, 26 eyes of 16 preperimetric glaucoma suspects, and 161 eyes of 124 glaucoma patients from the Diagnostics Innovations in Glaucoma Study with good quality high-density 6×6 mm2 macula optical coherence tomography angiography images were included. The diagnostic accuracy of SCP vessel density, projection-resolved DCP vessel density and GCC thickness were compared among groups. RESULTS Mean whole image vessel density (wiVD; % of area occupied by vessels containing flowing blood) in the SCP layer was highest in healthy eyes (49.7%), followed by glaucoma suspect eyes (46.0%), and glaucoma eyes (40.9%) (P

Purpose To evaluate the central visual field by microperimetry (MP), in early glaucoma. Methods Consecutive perimetrically experienced patients with a single nasal step or arcuate scotoma and 14 control eyes underwent MP. Retinal sensitivity on MP was mapped for frequency and depth of loss in the central 10° around fixation. Results Twenty-one eyes had a single nasal step and 19 eyes with single arcuate scotoma on standard automated perimetry (SAP), with central 10° being normal on 30-2 and 10-2 perimetry. The average mean sensitivity on MP, in glaucomatous and control eyes was 11.8 ± 3.9 dB and 16.6 ± 1.2 dB, respectively, P = 0.0004. The average mean defect on MP-1, in glaucomatous and control eyes was -6.5 ± 2.0 dB and -3.0 ± 1.2 Db, respectively, P = 0.05. The corresponding retinal hemisphere showed significant defects in MP. In eyes with single nasal steps, an absolute scotoma was seen in 14-28% of eyes 8-10° off fixation, moderate to mild defects were seen in 10-52% eyes, and 10% eyes showed involvement up to 4° from the fixation. Eyes with arcuate scotoma had an absolute scotoma on MP in 95% of eyes, 6-10° from fixation, with extension up to 2° from fixation in 21%. In glaucomatous eyes, the normal hemisphere on SAP showed a mild defect on MP in 43%. Control eyes did not show any defect in SAP or MP. Conclusion A significant loss of central retinal sensitivity is recorded on MP in early glaucomatous neuropathy as compared to SAP. Paramacular absolute defects were seen at 6-10° from fixation.

Purpose. We examined the relationships between pattern electroretinogram and optical coherence tomography derived optic nerve head measurements, after controlling for disc area. Methods. Thirty-two eyes from 20 subjects with preperimetric glaucoma underwent pattern electroretinogram and optical coherence tomography. Pattern electroretinogram parameters (Magnitude, MagnitudeD, and MagnitudeD/Magnitude ratio) and optic nerve head measurements (rim area, average cup to disc ratio, vertical cup to disc ratio, cup volume, retinal nerve fiber layer thickness sectors, and Bruch’s membrane opening-minimum rim width thickness sectors) were analyzed after controlling for disc area. Results. Magnitude and MagnitudeD were significantly associated with rim area (r ≥ 0.503, p ≤ 0.004 ). All pattern electroretinogram parameters significantly correlated with Bruch’s membrane opening-minimum rim width sectors—temporal superior and nasal inferior (r = 0.400, p = 0.039 )—and retinal nerve fiber layer sectors—superior, nasal superior, and inferior (r ≥ 0.428, p ≤ 0.026 ). Magnitude and MagnitudeD explained an additional 26.8% and 25.2% of variance in rim area (B = 0.174 (95% CI: 0.065, 0.283), p = 0.003 , and B = 0.160 (95% CI: 0.056, 0.265), p = 0.004 ), respectively. MagnitudeD and MagnitudeD/Magnitude ratio explained an additional 13.4% and 12.8% of the variance in Bruch’s membrane opening-minimum rim width global (B = 38.921 [95% CI: 3.872, 73.970], p = 0.031 , and B = 129.024 (95% CI: 9.589, 248.460), p = 0.035 ), respectively. All Bruch’s membrane opening-minimum rim width sectors and retinal nerve fiber layer sectors (nasal superior, nasal inferior, and inferior) were significantly correlated with rim area (r ≥ 0.389, p ≤ 0.045 ). Conclusion. PERG abnormalities can predict rim area loss in preperimetric glaucoma after controlling for disc area. We recommend controlling for disc area to increase diagnostic accuracy in early glaucoma.

Author(s): Suh, Min Hee; Na, Jeong Ho; Zangwill, Linda M; Weinreb, Robert N | Abstract: PurposeTo compare disease severity between preperimetric primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature dropout.Materials and methodsNinety-four eyes of 94 preperimetric POAG patients with β-zone parapapillary atrophy (βPPA) were categorized according to the presence of deep-layer microvasculature dropout defined as a complete loss of microvasculature within the choroid or scleral flange on optical coherence tomography angiography. Parameters representing disease severity, that is, visual field (VF) mean deviation (MD), global and sectoral (6-sector) retinal nerve fiber layer (RNFL) thickness, and other factors including age, focal lamina cribrosa (LC) defect, width of βPPA with and without Bruch membrane (BM) (βPPA+BM and βPPA-BM), and optic disc hemorrhage were compared between eyes with and without dropout.ResultsDeep-layer microvasculature dropout was observed in 33 preperimetric POAG eyes (35.1%). Eyes with dropout had significantly thinner RNFL in all areas except the inferonasal sector, worse VF MD, and higher prevalence of focal LC defect, and larger βPPA-BM (Pl0.05), whereas the 2 groups did not differ in age, disc hemorrhage, or βPPA+BM width (Pg0.05). In the multivariable logistic regression, worse VF MD [odds ratio (OR), 1.485; P=0.045], thinner RNFL (OR, 1.141; Pl0.001), and higher prevalence of focal LC defect (OR, 6.673; Pl0.001) were significantly associated with dropout.ConclusionsDeep-layer microvasculature dropout was observed in a considerable number of preperimetric POAG eyes, and worse disease severity was associated with dropout. Future studies elucidating the pathogenic role of deep-layer microvasculature dropout in the development and progression of glaucoma are warranted.

Purpose: To evaluate diagnostic ability of macular ganglion cell layer–inner plexiform layer (GCL-IPL) for detection of preperimetric glaucoma (PPG) and perimetric glaucoma and comparison with peripapillary RNFL. Methods: Three hundred and thirty seven eyes of 190 patients were enrolled (127 normals, 70 PPG, 140 perimetric glaucoma). Each patient underwent detailed ocular evaluation, standard automated perimetry, and spectral domain optical coherence tomography. Diagnostic abilities of GCL-IPL and RNFL parameters were determined. Data were compared using one-way analysis of variance, Pearson's Chi-square test, and area under the curve (AUC). Results: After adjusting for age, gender, and signal strength, all GCL-IPL and RNFL parameters except mean thickness and disc area differed significantly. Among GCL-IPL thicknesses, inferotemporal had the highest AUC (0.865) for classifying perimetric glaucoma from normals, inferior (0.746) for PPG from normals, and inferotemporal (0.750) for perimetric glaucoma from PPG. When using RNFL, inferior thickness had the highest AUC (0.922) in discriminating POAG from normal, while the same parameter had lower AUC (0.813) in discriminating PPG from normal. The average thickness had maximum AUC (0.775) for discriminating POAG from PPG. For discriminating perimetric glaucoma and normals, inferotemporal GCL-IPL had the highest strength (sensitivity 81.43% and specificity 77.96%), slightly lower than inferior RNFL thickness (sensitivity 87.85% and specificity 84.26%). The same parameters were sensitive in discriminating perimetric glaucoma from PPG (87.14% and 92.85%, respectively). However, their specificities were poor (56.43% both). Conclusion: RNFL had better diagnostic ability, when compared with GCL-IPL for detecting PPG and perimetric glaucoma. However, difference was small and may not be clinically relevant.

Background/aimsTo investigate whether subjects with preperimetric glaucoma exhibit decline in patient-reported vision-related quality of life (QoL) compared with healthy individuals.MethodsThis cross-sectional study included 45 patients with preperimetric glaucoma, 102 patients with perimetric glaucoma and 81 healthy controls. Perimetric glaucoma was defined by the presence of repeatable abnormal standard automated perimetry tests and corresponding optic nerve damage in at least one eye. Preperimetric glaucoma was defined based on the presence of retinal nerve fibre layer (RNFL) loss as detected by spectral-domain optical coherence tomography in the absence of visual field loss. Patient-reported QoL was measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25).ResultsPatients with preperimetric glaucoma had significantly thinner average RNFL in the better eye compared with controls (79.9±9.2 µm vs 97.8±8.6 µm; pConclusionContrary to patients with perimetric damage, preperimetric glaucoma does not seem to be associated with loss in QoL. Prevention of disability from glaucoma may benefit from early diagnosis during a ‘window of opportunity’ given by detecting structural loss before visual field damage.

Purpose To evaluate the ability of macular and multifocal (mf) pattern electroretinogram (PERG) to differentiate preperimetric glaucoma (PG) and glaucoma with hemifield loss (GHL) from controls, to compare the discrimination ability of PERG and fourier-domain optical coherence tomography (FD-OCT), and to assess the relationship between measurements. Patients and methods Standard automated perimetry, steady-state and transient PERG and mfPERG measurements were obtained from PG (n=14, 24 eyes), GHL (n=5, 7 eyes), and controls (n=19, 22 eyes). Circumpapillary retinal nerve fiber layer (cpRNFL), full-thickness macula, and segmented macular layer thicknesses on FD-OCT were investigated. Measurements were compared using mixed effects linear models. The relationships between measurements and the diagnostic performance of each technology were assessed. Results Compared with controls, average P50 peak time transient PERG responses were reduced in PG and GHL, whereas average latency and amplitude steady-state and mfPERG responses were abnormal only in GHL. cpRNFL and macular thickness measurements in PG and GHL differed significantly from controls. A significant relationship was found between PERG and most FD-OCT or SAP parameters. Partial least squares discriminant analysis revealed that OCT parameters, along with mfPERG and transient PERG parameters had similar ability to discriminate PG and GHL from healthy controls. Conclusions PERG and OCT parameters may be abnormal, with significant correlations between measurements, in PG eyes. Both technologies may be useful for detection of early glaucoma.

Purpose: To evaluate the measurements of the peripapillary retinal neurofiber layers (RNFL) and the ganglion cells complex (GCC) obtained by Optical Coherence Tomography (OCT) in eyes with preperimetric open-angle glaucoma. Methods: One hundred and forty eyes of 75 patients (21 male and 54 female), 80 eyes with preperimetric glaucoma (PPG) (45 patients) and 60 normal eyes (30 subjects) were included in this study. Automated visual field examination was done to all participants using Humphrey field analyzer, program 30-2. The GCC thickness and peripapillary RNFL thickness were measured using RTVue-100 (Optivue, Inc., Fremont, CA). The areas under ROC (receiver operating characteristic)—curves (AUCs) were defined for all examined GCC and RNFL parameters. Results: GCC of the eyes with PPG was significantly thinner than GCC of the normal eyes: (89.58 vs 97.82 microns, P < 0.001). There was no significant difference between upper and lower GCC halves in both study groups. We found a reduction of RNFL thickness in glaucomatous eyes (P < 0.001) compared with normals. AUCs for GCC parameters in eyes with PPG were larger than AUCs for RNFL parameters. Conclusion: Our study showed that the peripapillary RNFL and GCC thickness are lower in preperimetric glaucoma than in normal eyes. Despite the fact that GCC measurements (especially GLV) show better AUC than peripapillary measurements, we suggest that two scans (GCC and ONH) put together are superior in detecting early structural glaucomatous damage. Several diagnostic parameters should be considered in the clinical diagnosis of preperimetric glaucoma.

To evaluate an effective functional strategy for detecting glaucomatous damage of the macula in preperimetric to perimetric glaucoma.Cross-sectional study.Preperimetric glaucoma patients (n = 102) and perimetric glaucoma patients (n = 88) with isolated paracentral scotoma or combined paracentral scotoma were enrolled in this study. Global and sectoral mean sensitivities (MS) were evaluated using 10-2 standard automated perimetry (SAP) with a stimulus of sizes III (0.43-degree diameter) and V (1.72 degrees), and 10-2 Matrix perimetry with a stimulus of 2 degrees. Ganglion cell-inner plexiform layer (GCIPL) was measured using spectral-domain optical coherence tomography.The percentage of significantly depressed visual field (VF) points5% and1% in the pattern deviation plot was higher with frequency doubling technology (FDT) 10-2 than with SAP 10-2 III in patients with preperimetric glaucoma (both P.001). Using FDT 10-2 tests, the global structure-function correlation was superior to SAP 10-2 (III or V) in both preperimetric and perimetric glaucoma. Topographic structure-function relationships for each VF test were more favorable with the FDT 10-2 test. The preperimetric glaucoma patients showing VF abnormalities on FDT 10-2 or SAP 10-2 (III) showed thinner average, minimum, superior, inferior, and inferotemporal GCIPL thicknesses than in those without VF abnormalities (all P.05).FDT 10-2 was found to detect functional damage of the macula early in preperimetric glaucoma, and to perform better than with SAP 10-2 (size III or V) from preperimetric to perimetric glaucoma in the structure-function relationship. FDT 10-2 can be considered a useful tool to detect glaucomatous damage of the macula early and appropriately.

Background/aimsTo investigate the relationship between gaze tracking (GT) results and ocular surface condition in glaucoma.MethodThe Humphrey 24–2 visual field (VF) was measured in 34 eyes of 30 patients with open-angle glaucoma without VF damage. Tear break-up time, Schirmer’s test, tear meniscus volume (TMV) and presence of superficial punctate keratopathy (SPK) were also measured in order to describe the condition of the ocular surface. Various GT parameters were calculated: the average frequency of eye movements per stimulus between 1° and 2° (move1-2), the average frequency of eye movements per stimulus between 3° and 5° (move3-5), the average frequency of eye movements per stimulus more than 6° (move≥6), the average tracking failure frequency per stimulus (TFF) and the average blinking frequency. The relationship between GT parameters, reliability indices and ocular surface measurements was investigated using linear mixed modelling.ResultsSPK was positively associated with high rates of move3-5 (coefficient=0.12 for SPK+, p=0.003) and move≥6 (coefficient=0.052 for SPK+, p=0.023). High TMV was significantly related to TFF (coefficient=0.37, p=0.023). Fixation losses, false-positives and false-negatives were not significantly associated with any GT parameters or ocular surface measurements.ConclusionSPK is associated with increased frequency of eye movements (move3-5 and move≥6). In addition, large TMV is associated with increased rate of TFF. Careful attention should be paid when interpreting GT parameters in patients with SPK or a large TMV.

Aims To evaluate the long-term clinical course of normotensive preperimetric glaucoma (PPG). Methods We retrospectively analysed 130 eyes of 130 patients initially diagnosed as having preperimetric normal tension glaucoma and followed these cases for at least 5 years with reliable visual field (VF) examinations by standard automated perimetry. When the VF defect (VFD) met Anderson-Patella’s criteria on three or more consecutive examinations, and consistently met the criteria on subsequent examinations, we concluded that a glaucomatous VFD was present. Predictive factors for developing a VFD were assessed. Results Seventy-one eyes (54.6%) developed a glaucomatous VFD during the follow-up period. The mean deviation slope varied from −0.90 to 0.41 dB/year. A Cox proportional hazard model showed that having a greater initial pattern SD (p=0.005), the presence of optic disc haemorrhage (p=0.022) and higher mean intraocular pressure (IOP) prior to developing a VFD (p=0.039) were related to developing a VFD. Conclusions Our findings confirmed that the mean IOP, but not the IOP fluctuation, is strongly associated with the development of a VFD in cases of PPG.

Purpose To differentiate the visual fields (VFs) of preperimetric open-angle glaucoma (OAG) patients from the VFs of healthy eyes using a deep learning (DL) method. Design Cohort study. Participants One hundred seventy-one preperimetric glaucoma VFs (PPGVFs) from 53 eyes in 51 OAG patients and 108 healthy eyes of 87 healthy participants. Methods Preperimetric glaucoma VFs were defined as all VFs before a first diagnosis of manifest glaucoma (Anderson-Patella's criteria). In total, 171 PPGVFs from 53 eyes in 51 OAG patients and 108 VFs from 108 healthy eyes in 87 healthy participants were analyzed (all VFs were tested using the Humphrey Field Analyzer 30-2 program; Carl Zeiss Meditec, Dublin, CA). The 52 total deviation, mean deviation, and pattern standard deviation values were used as predictors in the DL classifier: a deep feed-forward neural network (FNN), along with other machine learning (ML) methods, including random forests (RF), gradient boosting, support vector machine, and neural network (NN). The area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of discrimination for each method. Main Outcome Measures The AUCs obtained with each classifier method. Results A significantly larger AUC of 92.6% (95% confidence interval [CI], 89.8%–95.4%) was obtained using the deep FNN classifier compared with all other ML methods: 79.0% (95% CI, 73.5%–84.5%) with RF, 77.6% (95% CI, 71.7%–83.5%) with gradient boosting, 71.2% (95% CI, 65.0%–77.5%), and 66.7% (95% CI, 60.1%–73.3%) with NN. Conclusions Preperimetric glaucoma VFs can be distinguished from healthy VFs with very high accuracy using a deep FNN classifier.

Aim To evaluate the diagnostic ability of macular ganglion cell-inner plexiform layer (GCIPL) thickness obtained by spectral-domain optical coherence tomography (SD-OCT) in discriminating non-highly myopic eyes with preperimetric glaucoma (PPG) from highly myopic healthy eyes. Methods A total of 254 eyes, including 76 normal controls (NC), 116 eyes with high myopia (HM) and 62 non-highly myopic eyes with PPG were enrolled. The diagnostic ability of OCT parameters was accessed by the areas under the receiver operating characteristic (AUROC) curve in two distinguishing groups: PPG eyes with non-glaucomatous eyes including NC and HM (Group 1), and PPG eyes with HM eyes (Group 2). Differences in diagnostic performance between GCIPL and RNFL parameters were evaluated. Results The minimum (AUROC curve of 0.782), inferotemporal (0.758) and inferior (0.705) GCIPL thickness were the top three GCIPL parameters in discriminating PPG from non-glaucomatous eyes, all of which had statistically significant lower diagnostic ability than average RNFL thickness (0.847). In discriminating PPG from HM, the best GCIPL parameter was minimum (0.689), statistically significant lower in diagnostic ability than average RNFL thickness (0.789) and three other RNFL thickness parameters of temporal and inferotemporal clock-hour sectors. Conclusion The minimum GCIPL thickness is the best GCIPL parameter to detect non-highly myopic PPG from highly myopic eyes, whose diagnostic ability is inferior to that of average RNFL thickness and RNFL thickness of several temporal and inferotemporal clock-hour sectors. The average RNFL thickness is recommended for discriminating PPG from highly myopic healthy eyes in current clinical practice in a Chinese population.

Background To evaluate the diagnostic ability of macular ganglion cell asymmetry to diagnose preperimetric glaucoma (PPG), using Cirrus spectral domain optical coherence tomography (OCT). Methods This prospective study included 67 eyes of 67 patients with PPG and 67 eyes of 67 age- and refractive error-matched controls. We measured circumpapillary RNFL (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness and optic nerve head (ONH) parameters using OCT. Macular ganglion cell asymmetries were expressed as absolute difference and ratios between inferior hemisphere and superior hemisphere, inferotemporal (IT) and superotemporal (ST), IT and superonasal (SN), IT and inferonasal (IN), ST and IN as well as temporal and nasal. An asymmetry index was assigned by taking the absolute value of log10 of the ratio. The area under the receiver operating characteristics curve (AUROC), partial AUROC (pAUROC) ≥ specificities 90 and 95%, cutoff values and sensitivities at specificities 90 and 95% was analyzed. Results Parameters with largest AUROCs were IT GCIPL thickness (0.784), average RNFL thickness (0.767), and average C/D (0.746). For macular asymmetry parameters, log IT/SN index had the largest AUROC (0.734), followed by log IT/IN index (0.725), and absolute difference of IT−SN GCIPL thickness (0.715). Performance was comparable between the best measures of asymmetry analysis (log IT/SN index) and those of cpRNFL, GCIPL, and ONH parameters (all P > 0.05). The IT/SN asymmetry index not only had the largest pAUROC based on the pAUROCs ≥90 and 95% specificity (0.044 and 0.019) but also had the highest diagnostic sensitivity at 90 and 95% specificities (52.2 and 46.3%). Conclusions GCIPL asymmetry measurements have diagnostic ability comparable to cpRNFL, GCIPL, and ONH analysis for PPG. The best macular ganglion cell asymmetry parameter was IT/SN asymmetry index, which could be a new parameter to detect early structural changes in PPG. Electronic supplementary material The online version of this article (10.1186/s12886-018-1019-4) contains supplementary material, which is available to authorized users.

PurposeTo evaluate choroidal structural changes in glaucoma using choroidal vascularity index (CVI) compared to healthy subjects.MethodsThis retrospective study included 56 patients with open angle glaucoma (OAG), 50 patients with preperimetric glaucoma (PPG) and 50 age-matched healthy eyes. Choroidal images were binarized into luminal area (LA) and stromal area. CVI was defined as the ratio of LA to total circumscribed choroid area (TCA). Mean choroidal thickness (CT) and mean CVI between glaucoma patients and healthy subjects were compared.ResultsOAG and PPG eyes showed smaller LA (0.45 ± 0.13 ㎟ vs. 0.47 ± 0.11 ㎟, p = 0.04). In multivariate regression analysis, CVI of both OAG (64.34±0.19%, p = 0.001) and PPG (65.37±0.15%, p = 0.001) were significantly lower than healthy eyes (68.81±0.14%).ConclusionEyes with glaucoma demonstrated reduced CVI compared with healthy eyes. CVI may be a potential noninvasive tool for studying vascular dysfunction in glaucoma.

Purpose We assessed the ability to detect preperimetric glaucoma (PPG) based on asymmetry in the thickness of the macular inner retinal layers measured by spectral-domain optical coherence tomography. Methods We studied 45 normal eyes and 50 PPG eyes retrospectively. Three-dimensional optical coherence tomography macular area scans were used to obtain the thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer/inner plexiform layer (GCL/IPL), and ganglion cell complex (GCC). We calculated the thickness differences between the upper and lower macular hemispheres for the corresponding superpixels, then evaluated the mean absolute value of the thickness differences and the number of superpixels in which the thickness difference was greater than X µm, where X is an integer number from 1 to 10. Areas under the receiver operating characteristic curves (AUCs) for their PPG diagnostic performances were compared to the average thickness measurements of the total and hemiretinal sectors. X was determined at the maximum AUC value. Results The AUC for the mean absolute value of the difference in GCL/IPL thickness (0.923) was higher than the difference in RNFL and GCC thickness (0.710 and 0.905, respectively). The AUC for the number of superpixels in which the GCL/IPL thickness difference was greater than 8 µm (X = 8) was 0.914. The ability to diagnose PPG using these GCL/IPL parameters was statistically higher than for total or superior and inferior hemiretinal GCL/IPL thicknesses. Conclusions Asymmetry in the thickness of the GCL/IPL shows good PPG diagnostic performance. Translational relevance This approach would be useful in the early detection of glaucoma.

PurposeTo investigate the clinical significance of color visual acuity (CVA) in preperimetric glaucoma (PPG) and open-angle glaucoma (OAG).MethodsA total of 123 eyes of 73 subjects (22 normal eyes, 14 PPG eyes, and 87 OAG eyes; mean age: 44.9 ± 10.1 years, age range: 21-64 years) were enrolled. CVA was tested for red, green-yellow, blue-green and blue-purple with a newly developed test.ResultsThere was no statistical difference in clinical background factors, including age, sex, intraocular pressure, or spherical equivalent between the three groups. Red VA and blue-green VA were significantly worse in the OAG eyes than in the normal eyes (P = 0.008 and P = 0.015, respectively), although green-yellow VA and blue-purple VA were not significantly worse. Furthermore, red VA and blue-green VA were significantly correlated with MD in a group of eyes with either PPG or OAG (r = -0.23, P = 0.023; r = -0.25, P = 0.012, respectively), but green-yellow VA and blue-purple VA were not.ConclusionRed VA and blue-green VA were detectably worse in eyes with OAG, in close association with the degree of functional loss. This suggests that measuring CVA with the new color test described here may be a promising supplement to existing methods of detecting glaucoma and evaluating its severity.

Milena Pahlitzsch,1 Necip Torun,1 Carl Erb,2 Jeanette Bruenner,1 Anna Karina B Maier,1 Johannes Gonnermann,1 Eckart Bertelmann,1 Matthias K J Klamann1 1Department of Ophthalmology, University Medicine Charité, Campus Virchow Clinic, Berlin, 2Augenklinik am Wittenbergplatz, Berlin, Germany Purpose: To assess the correlation between the disc damage likelihood scale (DDLS) objectively measured by a non-mydriatic fundus camera, Heidelberg Retina Tomograph 3, and optic coherence tomography in preperimetric glaucoma. Methods: One-hundred-twenty-five patients with preperimetric primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (n=30) were included (mean age 58.9±15.9 years). All three devices graded the optic disc topography: Diagnosis 1 was defined as “outside normal limits”, while Diagnosis 2 as “borderline or outside normal limits”. Results: For Diagnosis 1, a significant correlation was shown between DDLS and Moorfields regression analysis (P=0.022), and for Diagnosis 2 with glaucoma probability score analysis (P=0.024), in POAG. In pseudoexfoliation glaucoma, DDLS did not correlate significantly with Heidelberg Retina Tomograph 3 and optic coherence tomography. Regarding the area under the curve the highest predictive power was demonstrated by the objective DDLS (0.513–0.824) compared to Burk (0.239–0.343) and Mikelberg (0.093–0.270) coefficients. Conclusions: The DDLS showed a significant correlation to the Moorfields regression analysis in preperimetric POAG. The objective DDLS showed the highest predictive power and thus is an additive tool in diagnosing preperimetric glaucoma. Keywords: DDLS, preperimetric glaucoma, optic coherence tomography, stereophotography, Heidelberg Retina Tomograph

It is generally acknowledged that structural loss can precede functional loss in some patients with early glaucoma. However, conventional standard automated perimetry (SAP) has limitations in the detection of functional loss, especially in the macular area. This study explores visual field loss in the macular areas of patients with preperimetric glaucoma exhibiting structural thinning in the area by examining the correlations between the ganglion cell-inner plexiform layer (GCIPL) and the results of matrix frequency-doubling technology (FDT) 10-2 tests. The structure-function relationships between the GCIPL thicknesses and the mean sensitivities (MSs) of the corresponding areas based on conventional SAP 24-2, FDT 10-2, and FDT 24-2 were examined in 62 patients. The highest correlation was found for FDT 10-2 (r = 0.544, P P = 0.002) and SAP (r = 0.346, P = 0.007). The correlation coefficients between each GCIPL sector and the corresponding central MS according to FDT 24-2 and 10-2 were all statistically significant, and the correlations were significantly stronger for FDT 10-2 than 24-2 in the inferior and inferonasal sectors. In conclusion, preperimetric glaucoma patients with structural loss in the macula as indicated by GCIPL thinning also exhibited functional loss as revealed by FDT 10-2, and the functional loss was less evident with conventional SAP.

This paper presents an automated technique to detect optical disc (OD) regions and to locate clipping circles to separate OD and non-OD regions using fundus images. After surveys on different OD detection techniques, a set of image and geometric processing techniques is selected and implemented. Several public fundus images with different ophthalmologic diseases are used to experiment and to verify the performance of the proposed algorithm. The proposed algorithm tends to locate clipping circles properly by enclosing OD regions with fundus images of healthy patients. However, the algorithm is not good enough to process fundus images of different ophthalmologic conditions. The overall performance of the proposed algorithm is discussed along with several experimental results. Several future research issues are also addressed.

To characterize preperimetric retinal nerve fiber layer (RNFL) defects on speckle noise-reduced spectral-domain optical coherence tomography (SD-OCT), and to determine whether detection of preperimetric RNFL defects can be improved by speckle noise reduction.Thirty-two eyes of 32 patients with preperimetric glaucoma and 30 normal eyes of 30 volunteers underwent complete ophthalmic examinations and scanning by speckle noise-reduced SD-OCT (Spectralis), single-scan SD-OCT (RTVue-100), and single-scan time-domain (Stratus) OCT.All 40 RNFL defects identified by photography had angular widths30 degrees and no disruption of RNFL reflectivity on Spectralis. Circumpapillary RNFL (cpRNFL) boundaries were accurately determined by Spectralis for 38 (95.0%) of the 40 defects, by RTVue-100 for 25 (62.5%), and by Stratus OCT for 23 (57.5%). Sensitivity for the detection of RNFL defects (cpRNFL thinning to1% of normal for an age-matched database) was 15% for Stratus, 42.5% for RTVue, and 47.5% for Spectralis on sector maps and significantly higher for SD-OCT on temporal-superior-nasal-inferior-temporal (TSNIT) thickness graphs: RTVue-100 (57.5%; P=0.031) and Spectralis (90.0%; P=0.0001). On the basis of TSNIT thickness graphs, sensitivity for the detection of RNFL defects was significantly higher for Spectralis compared with RTVue-100 (P=0.001) and Stratus (P=0.0005). Spectralis TSNIT graphs were more sensitive (P=0.001) for glaucoma detection without significant reduction (P=0.125) in specificity compared with Spectralis sector maps.Our results suggest that accurate measurement of cpRNFL thickness by speckle noise-reduced SD-OCT and a comparison of the results with normative database using TSNIT graphs are required to improve the sensitivity for detecting preperimetric RNFL defects.

Purpose The purpose of this study was to investigate the long-term clinical course of normotensive preperimetric glaucoma (PPG). Methods The medical records of 71 eyes of 71 patients with normotensive PPG who underwent intraocular pressure (IOP)-lowering therapy were reviewed retrospectively. The patients had been regularly followed up at 3- to 6-month intervals between 1996 and 2011. Progression was evaluated by comparing the structural changes of serial stereoscopic colour disc and red-free retinal nerve fibre layer (RNFL) photographs and by comparing serial visual field (VF) test results for functional changes. Results Over an average follow-up period of 6.8 years, 41 eyes (57.7%) showed progression in either structural or functional evaluation. Disc haemorrhage (DH) was observed significantly more frequently in the progressing group (p

To investigate structural measurements of the macular area in preperimetric glaucoma (PG) patients using spectral domain optical coherence tomography with two functional measurements [10-2 Humphrey visual field (HFA) and 10-2 Microperimeter-1 (MP-1)] and by macular symmetry testing. Fifteen eyes of 15 PG subjects with a retinal nerve fiber layer defect in the inferior hemisphere and 15 eyes of 15 normal control subjects were enrolled. Macular symmetry testing was performed between the superior and inferior zones by comparing zone thickness in each hemisphere. Perimetric sensitivity asymmetry was calculated with two functional measurements. Structure–function relationships between macular symmetry testing and the mean retinal sensitivity of the corresponding hemifield or perimetric sensitivity asymmetry were calculated using Spearman’s rank correlation and linear regression. Macular zone thickness in the abnormal hemispheres was significantly less than that in normal hemispheres in PG eyes and the corresponding hemispheres in control eyes (P

Background To evaluate and compare the utility of ganglion cell complex with peripapillary retinal nerve fibre layer and optic nerve head measurements for detection of localized defects in patients with preperimetric glaucoma using spectral-domain optical coherence tomography. Design Prospective study. Participants Preperimetric glaucoma patients. Methods A total of 105 eyes with preperimetric glaucoma and 68 age- and refractive error-matched control eyes were enrolled. The ability to detect localized retinal nerve fibre layer defects by RTVue-100 spectral-domain optical coherence tomography (Optovue, Inc., Fremont, CA, USA) was assessed calculating the areas under receiver operating characteristic curves. Main Outcome Measures The ability to detect localized retinal nerve fibre layer defects by spectral-domain optical coherence tomography. Results Global volume loss and superior ganglion cell complex thickness showed the largest area under receiver operating characteristic curve values (both areas under receiver operating characteristic curves 0.84, P 0.02). Conclusions Ganglion cell complex thickness was significantly reduced in eyes with preperimetric glaucoma. Ganglion cell complex imaging using spectral-domain optical coherence tomography may be a useful ancillary modality for detection of early macular changes in glaucomatous eyes with localized retinal nerve fibre layer defects.

Purpose The purpose of the study was to evaluate the structure-function relationship and diagnostic value of retinal nerve fiber layer (RNFL) Area Index from the RNFL thickness deviation map of Cirrus SD-OCT. Methods : A total of 84 normal control eyes, 88 preperimetric eyes, and 146 perimetric glaucoma eyes were analyzed. The area of the RNFL defect in the RNFL thickness deviation map was expressed as RNFL Area Index: 1-[area of superpixels coded in red/(6×6-optic disc area)]. The diagnostic performance of RNFL Area Index and that of circumpapillary RNFL thickness were compared with the area under the receiver operating characteristic curve. Regression analysis was performed with the OCT measurements and the mean retinal sensitivity of the corresponding fields. Results : The RNFL Area Index was 96.63±14.22%, 89.89±14.54%, and 81.65±17.11% in the control, preperimetric, and perimetric glaucoma group. The RNFL Area Index had the largest area under the receiver operating characteristic curve to discriminate preperimetric and perimetric glaucoma from normal eyes. The RNFL Area Index showed a strong correlation with circumpapillary RNFL thicknesses in perimetric glaucoma, however, only modest correlation was shown in preperimetric glaucoma. In preperimetric glaucoma, the RNFL Area Index had the strongest associations with mean retinal sensitivity and it was significantly different from those of circumpapillary RNFL thicknesses. Conclusions : The RNFL Area Index showed better diagnostic performance for glaucoma detection and stronger structure-function relationships in preperimetric glaucoma. The RNFL thickness deviation map of Cirrus SD-OCT may be useful to correlate with functional loss in early glaucomatous eyes.

To evaluate functional progression in preperimetric glaucoma (PPG) with disc hemorrhage (DH) and to determine the time interval between the first-detected DH and development of glaucomatous visual field (VF) defect. A total of 87 patients who had been first diagnosed with PPG were enrolled. The medical records of PPG patients without DH (Group 1) and with DH (Group 2) were reviewed. When glaucomatous VF defect appeared, the time interval from the diagnosis of PPG to the development of VF defect was calculated and compared between the two groups. In group 2, the time intervals from the first-detected DH to VF defect of the single- and recurrent-DH were compared. Of the enrolled patients, 45 had DH in the preperimetric stage. The median time interval from the diagnosis of PPG to the development of VF defect was 73.3 months in Group 1, versus 45.4 months in Group 2 (P = 0.042). The cumulative probability of development of VF defect after diagnosis of PPG was significantly greater in Group 2 than in Group 1. The median time interval from first-detected DH to the development of VF defect was 37.8 months. The median time interval from DH to VF defect and cumulative probability of VF defect after DH did not show a statistical difference between single and recurrent-DH patients. The median time interval between the diagnosis of PPG and the development of VF defect was significantly shorter in PPG with DH. The VF defect appeared 37.8 months after the first-detected DH in PPG.

To determine the relationship between visual fields and retinal structures measured with spectral-domain optical coherence tomography in preperimetric glaucoma (PPG).Twenty-six eyes of 26 patients with PPG and 20 healthy eyes of 20 volunteers were included. All patients underwent Heidelberg retina tomography-2 (HRT2), standard automated perimetry (SAP), frequency-doubling technology (FDT) perimetry, and RTVue-100. SAP and FDT indices, HRT parameters, and circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) thicknesses were correlated using Pearson's test. Areas under the receiver operating characteristic curves (AUROCs) and sensitivity/specificity based on each parameter's definition of abnormalities were compared between parameters.Significant differences were found in FDT-MD, FDT-PSD, SAP-PSD, cpRNFL, and mGCC parameters (p0.001-0.015), but not in SAP-MD or HRT parameters, between PPG and control groups. Significant correlations were not found between visual field indices and structural parameters, except between FDT-MD and HRT rim area (r = 0.450, p = 0.021) and between FDT-PSD and temporal cpRNFL thickness (r = 0.402, p = 0.021). AUROCs for cpRNFL (p = 0.0047-0.033) and mGCC (p = 0.0082-0.049) parameters were significantly better than those of HRT parameters, whereas significant differences were not found between FDT indices and cpRNFL or mGCC parameters or between cpRNFL and mGCC parameters. Adding average cpRNFL or mGCC thickness to FDT-MD significantly increased sensitivity compared to single parameters (p = 0.016-0.031).Structural and functional parameters were poorly correlated but complementary for glaucoma detection in PPG. Combining these parameters may improve PPG diagnosis.

Hintergrund: Die normale Weis-auf-Weis computerisierte statische Perimetrie ist fur beginnende Gesichtsfelddefekte bei Patienten mit Glaukomverdacht nicht sehr sensibel. Zu den neueren Verfahren gehort die Heidelberg-Edge-Perimetrie ® (HEP), bei der das zentrale Gesichtsfeld mit einem Flicker-definierten Stimulus (FDF) getestet wird. Patienten und Methoden: Bei 90 Augen von 50 Patienten (mittleres Alter 59 ± 14) mit okularer Hypertension und/oder verdachtiger Papille ohne nachweisbare Gesichtsfeldschaden in der Octopus ® -Perimetrie (Programm dG-2) erfolgte eine Untersuchung mittels Heidelberg-Edge-Perimeter ® . Der „mean defect“ (MD), die „pattern standard deviation“ (PSD) und der Glaucoma-Halbfeldtest (GHT) wurden errechnet und mit den Indices des Octopus ® verglichen. Ergebnisse: Bei 48 von 90 Augen (53 %) wurden trotz normaler Gesichtsfeldbefunde in der Octopus ® -Perimetrie (MD Schlussfolgerungen: Die Heidelberg-Edge-Perimetrie ® als neue Untersuchungsmethode scheint bei der Fruherkennung von Gesichtsfeldalterationen bei Patienten an der Grenze zwischen okularer Hypertension und beginnendem Glaukom sensibler zu sein als die herkommliche statische Perimetrie.

This study was performed to compare the effectiveness of scanning laser polarimetry with variable corneal compensation (GDx VCC) and optical coherence tomography (Stratus OCT) for the detection of loss of the retinal nerve fiber layer (RNFL) in preperimetric glaucomatous eyes.Sixty subjects with preperimetric glaucoma (60 eyes) and 60 normal subjects (60 eyes) were included. We measured the RNFL thickness with GDx VCC and Stratus OCT and analyzed the results by 12 clock hour RNFL measurements. The area under the receiver-operating characteristic curve was calculated, and the data from all clock hour segments were compared using regression analyses.The mean RNFL thickness for GDx VCC were 49.00 ± 17.23 μm and 59.4 ± 8.38 μm (p0.01), and for Stratus OCT, they were 86.43 ± 20.49 μm and 106.61 ± 9.57 μm (p0.01) in the patients with preperimetric glaucoma and normal group, respectively. The mean RNFL thickness for the clock hour evaluations were significantly different between the patients with preperimetric glaucoma and the normal group (p0.05). In preperimetric glaucoma, the area under the receiver-operating characteristic curve was the highest for the 12 clock hour RNFL thickness for GDx VCC (0.905) and the 7 clock hour RNFL thickness for Stratus OCT (0.903). GDx VCC and Stratus OCT RNFL measurements had significantly high correlations in the superior and inferior quadrants (r0.750) and low correlation at the nasal quadrant (r = 0.210).Both GDx VCC and Stratus OCT instruments had similar correlations at each clock hour segment, and both were useful in the early detection of patients with preperimetric glaucoma.

Purpose: To present a revised interpretation of the work-up data that enabled diagnosis of preperimetric glaucoma (PPG) at the first examination. Methods: a) Literature analysis on PPG; b) 6-year follow-up of a glaucoma-suspect patient. Results: Two new concepts may be adapted: (a) the objective finding of retinal nerve fiber layer (RNFL) thinning below the normal border in the opposing typical glaucoma locations, the inferior and superior quadrants, and in a non-diffuse pattern, appears asymptomatically and simultaneously only in glaucoma; and (b) the imaging-related RNFL thickness may be considered the reference glaucoma standard, whereas the suspicious early glaucomatous optic neuropathy, having a potential diagnostic inaccuracy, would serve as a complementary revealing finding. That approach enabled, in retrospect, a first-visit diagnosis of low-tension PPG in the patient. Diagnosis was confirmed after 6 years, when cecocentral scotoma and further RNFL thinning emerged despite treatment. Conclusions: A revised approach enabled PPG diagnosis during the first visit.

Purpose We evaluated the performance of low contrast achromatic (LLA) multifocal visual evoked potentials (mfVEP) in preperimetric glaucoma and compared its diagnostic performance to other early diagnostic tests. We identified the clinically most useful tests and combinations in preperimetric glaucoma. Methods We studied 59 patients with at least one glaucomatous disc, with normal, reliable visual fields in that eye, and 17 normal controls. All participants underwent complete ophthalmic examination including Humphrey visual fields (HVF), short wavelength automated perimetry (SWAP), frequency doubling perimetry (FDT Matrix), Spectralis optical coherence tomography (OCT), Heidelberg retinal tomography (HRT 3), and color stereoscopic optic disc photographs. We recorded mfVEPs using LLA stimulation. Results We studied 85 eyes of 59 patients (64.89 ± 8.15 years) and 34 eyes of 17 controls (64.28 ± 13.06 years; P = 0.64). Heidelberg retinal tomography and LLA mfVEP demonstrated the best sensitivities (50.6% and 51.8%, respectively) in identifying preperimetric glaucoma, and were not significantly different from each other. Both tests had significantly better sensitivity than all other tests (P < 0.0001). Of the eyes, 76.5% were identified by the combination of (any one of) LLA mfVEP and HRT. Sensitivity of the combination was significantly better than any of the individual tests (P < 0.05 for all pairs), or any other combinations of tests, with better negative than positive predictive value. Conclusions The LLA mfVEP test identified approximately 50.6% eyes with preperimetric glaucoma, which was significantly higher than other perimetric methods, and similar to HRT. The combination of LLA mfVEP and HRT had exceptionally high sensitivity of 76.5% for preperimetric glaucoma.

To compare the abilities of retinal nerve fiber layer (RNFL) parameters of variable corneal compensation (VCC) and enhanced corneal compensation (ECC) algorithms of scanning laser polarimetry (GDx) in detecting various severities of glaucoma.Two hundred and eighty-five eyes of 194 subjects from the Longitudinal Glaucoma Evaluation Study who underwent GDx VCC and ECC imaging were evaluated. Abilities of RNFL parameters of GDx VCC and ECC to diagnose glaucoma were compared using area under receiver operating characteristic curves (AUC), sensitivities at fixed specificities, and likelihood ratios.After excluding 5 eyes that failed to satisfy manufacturer-recommended quality parameters with ECC and 68 with VCC, 56 eyes of 41 normal subjects and 161 eyes of 121 glaucoma patients [36 eyes with preperimetric glaucoma, 52 eyes with early (MD-6 dB), 34 with moderate (MD between -6 and -12 dB), and 39 with severe glaucoma (MD-12 dB)] were included for the analysis. Inferior RNFL, average RNFL, and nerve fiber indicator parameters showed the best AUCs and sensitivities both with GDx VCC and ECC in diagnosing all severities of glaucoma. AUCs and sensitivities of all RNFL parameters were comparable between the VCC and ECC algorithms (P0.20 for all comparisons). Likelihood ratios associated with the diagnostic categorization of RNFL parameters were comparable between the VCC and ECC algorithms.In scans satisfying the manufacturer-recommended quality parameters, which were significantly greater with ECC than VCC algorithm, diagnostic abilities of GDx ECC and VCC in glaucoma were similar.

Purpose To investigate the site specificity of visual field changes in eyes with normotensive preperimetric glaucoma (PPG), and to determine factors influencing visual field progression. Methods This prospective study comprised 84 eyes of 84 normotensive PPG patients followed for at least 16 months. Optic nerve head (ONH) blood flow was assessed with tissue-area mean blur rate (MBRT), derived from laser speckle flowgraphy. Total deviation (TD) was measured in each sector of the Garway-Heath map to evaluate the site specificity of visual field loss. Subjects with a TD slope in the first quartile were classified as progressive, and other subjects as nonprogressive. Linear and multiple regression analyses were performed to determine factors affecting visual field progression. Results TD in the superior sector significantly decreased in the subjects overall during the follow-up periods (-0.48 ± 1.92 dB/y, P = 0.025). Linear regression analysis showed that basal MBRT-inferior was correlated significantly with TD-superior slope (r = 0.332, P = 0.002). Furthermore, basal MBRT was significantly lower in this sector in the progressive than the nonprogressive group (P = 0.010). Multiple linear regression analysis revealed that basal MBRT-inferior was the only predictive factor for TD-superior slope (β = 0.329, P = 0.005). Conclusions These findings suggest that superior-sector visual field progression is most common in normotensive PPG eyes, and that reduced basal ONH blood flow is associated with visual field progression. Translational relevance These findings provide new insight into the involvement of ONH blood flow impairment in glaucoma pathogenesis, and demonstrate the importance of assessing ONH blood flow to determine visual field progression in normotensive PPG.

Purpose: To compare the diagnostic ability of the ganglion cell analysis (GCA) and retinal nerve fiber layer (RNFL) protocol on optical coherence tomography (OCT), to diagnose preperimetric glaucoma. Methods: A prospective, cross-sectional study of 275 adult patients including 47 early glaucoma (mean deviation better than -6.0 D), 150 glaucoma suspects (106 with suspicious discs and 44 ocular hypertensive (OHT), and 78 normal controls was done. Eligible participants were scanned with the spectral domain CirrusTM OCT (Carl Zeiss Meditec, Dublin, CA). Average peripapillary RNFL thickness and GCA measurements were obtained. Area under receiver operating characteristic (AROC) curves were used to evaluate discriminant value of both protocols to diagnose likely preperimetric glaucoma among glaucoma suspects. Results: Average RNFL and GCA were significantly thinner in glaucoma patients compared to glaucoma suspects and normal controls (P < 0.001). The RNFL was 92.26 ± 8.8 μ in normal controls, 87.9 ± 12.12 μ in glaucoma suspects and significantly thinner in POAG (70.29 ± 10.18 μ; P < 0.001). The GCA was 81.94 ± 6.17 μ in normal controls, 77.69 ± 9.03 μ in glaucoma suspects, and significantly thinner in POAG (69.36 ± 11.06 μ; P < 0.001). AROCs for discriminating glaucoma suspects from normal were modest, with no difference in AROC of average RNFL or GCA measurements (DeLong; P = 0.93). Average RNFL thickness had significantly greater AROC values than average GCA for discriminating glaucoma suspects (both suspicious discs and OHT) from glaucoma (P = 0.03 and 0.05, respectively. AROC for diagnosing glaucoma was significantly better (P = 0.02) for RNFL (0.88 ± 0.03) than GCA (0.77 ± 0.04). Conclusion: In the present time, GCA measurements, as provided by the SD-OCT, do not appear to outperform RNFL measurements in the diagnosis of preperimetric glaucoma.

PURPOSE To investigate the additive diagnostic role of spectral-domain optical coherence tomography (SD-OCT) and red-free retinal nerve fiber layer photography (RNFLP) in making clinical glaucoma diagnosis. METHODS Four diagnostic combination sets, including the most recent image from each measurement of 196 glaucoma eyes (including the 44 preperimetric glaucoma eyes) and 101 healthy eyes, were prepared: (1) stereo disc photography and Humphrey visual field (SH), (2) SH and SD-OCT (SHO), (3) SH and RNFLP (SHR), and (4) SHR and SD-OCT (SHRO). Each randomly sorted set was serially presented at 1-month intervals to five glaucoma specialists who were asked to evaluate them in a subjective and independent manner. The specialists' glaucoma-diagnostic performances based on the sets were then compared. RESULTS For each specialist, adding SD-OCT to SH or SHR increased the glaucoma-diagnostic sensitivity but not to a level of statistical significance. For one specialist, adding RNFLP to SH significantly increased the sensitivity. Each specialist showed a high level of specificity regardless of the diagnostic set. The overall sensitivity of all specialists' assessments was significantly increased by adding RNFLP or the combination of SD-OCT and RNFLP to SH (P < 0.001); however, adding SD-OCT to SH or SHR did not significantly increase the sensitivity. A similar relationship was noted also for the preperimetric glaucoma subgroup. CONCLUSIONS In contrast to RNFLP, SD-OCT did not significantly enhance the diagnostic accuracy of detecting glaucoma or even of preperimetric glaucoma. Our results suggest that, at least for glaucoma specialists, the additive diagnostic role of OCT is limited.

PURPOSE To compare the visual fields (VFs) of preperimetric open angle glaucoma (OAG) patients (preperimetric glaucoma VFs, PPGVFs) with the VFs of healthy eyes, and to discriminate these two groups by using the Random Forests machine-learning method. METHODS All VFs before a first diagnosis of manifest glaucoma (Anderson-Patella's criteria) were classified as PPGVFs. Series of VFs were obtained with the Humphrey Field Analyzer 30-2 program from 171 PPGVFs from 53 eyes in 51 OAG or OAG suspect patients and 108 healthy eyes of 87 normal subjects. The area under the receiver operating characteristic curve (AROC) in discriminating between PPGVFs and healthy VFs was calculated by using the Random Forests method, with 52 total deviation (TD) values, mean deviation (MD), and pattern standard deviation (PSD) as predictors. RESULTS There was a significant difference in MD between healthy VFs and PPGVFs (-0.03 ± 1.11 and -0.91 ± 1.56 dB [mean ± standard deviation], respectively; P < 0.001, linear mixed model) and in PSD (1.56 ± 0.33 and 1.97 ± 0.43 dB, respectively; P < 0.001). A significant difference was observed in the TD values between healthy VFs and PPGVFs at 25 (P < 0.001) of 52 test points (linear mixed model). The AROC obtained by using the Random Forests method was 79.0% (95% confidence interval, 73.5%-84.5%). CONCLUSIONS Differences exist between healthy VFs and VFs of preperimetric glaucoma eyes, which go on to develop manifest glaucoma; these two groups of VFs could be well distinguished by using the Random Forests classifier.

Purpose To compare the ability of Corrected Cluster Trend Analysis (CCTA) and Cluster Trend Analysis (CTA) with event analysis of Octopus visual field series to detect early glaucomatous progression. Methods One eye of 15 healthy, 19 ocular hypertensive, 20 preperimetric, and 51 perimetric glaucoma (PG) patients were investigated with Octopus normal G2 test at 6-month intervals for 1.5 to 3 years. Progression was defined with significant worsening in any of the 10 Octopus clusters with CCTA, and event analysis criteria, respectively. Results With event analysis, 9 PG eyes showed localized progression and 1 diffuse mean defect (MD) worsening. With CCTA, progression was indicated in 1 normal, 1 ocular hypertensive, and 1 preperimetric glaucoma eyes due to vitreous floaters, and 28 PG eyes including all 9 eyes with localized progression with event analysis. The locations of CCTA progression matched those found with event analysis in all 9 cases. In 17 of the remaining 19 eyes, progressing clusters matched the locations that were suspicious but not definitive for progression with event analysis. In the eye with diffuse MD worsening, CTA found significant progression for 7 clusters. For global MD progression rate, eyes worsened with CCTA only did not differ from the stable eyes but had significantly smaller progression rates than the eyes progressed with event analysis (P=0.0002). Conclusions In PG, Octopus CCTA and CTA are clinically useful to identify early progression and areas suspicious for early progression. However, in some eyes with no glaucomatous visual field damage, vitreous floaters may cause progression artifacts.

Цел: Да се определят диагностичните възможности на Rarebit периметрията за установяване на ранни функционални промени при първична откритоъгълна глаукома. Методи: Включени са общо 47 очи разпределени в две групи: 23 очи с предпериметрична глаукома (ППГ) и контролна група от 24 очи, изследвани чрез Rarebit периметрия (РБП) и стандартна автоматична периметрия (САП). За оценка на разликите между групите са използвани Kruskal Wallis Test, Mann-Whitney Test, Fisher's Exact Test. Чувствителността и специфичността на РБП за установяване на ранни глаукомни промени е оценена чрез ROC анализ с помощта на различни алгоритми. Резултати: Средните стойности за МНR за контролите и групата ППГ са съответно: 94.71% (SD 2.58); 87.61% (SD 4.80). Разликите в стойностите на МНR между групите са статистически значими (Мann-Whitney Test, р

Purpose To evaluate and compare the Glaucoma detection ability of macular GCC thickness with that of peripapillary RNFL measured by FD-OCT (RTVue 100. Optovue Inc, CA) in patients with Preperimetric Glaucoma (PPG) and Perimetric Glaucoma (PG) at early stage according to Hodapp-Parrish-Anderson classification. Methods 89 patients (178 eyes: 70 PPG, 56 PG and 52 healthy) were enrolled in this cohort study. Each subject underwent complete ophthalmic examination and imaging of mGCC, pRNFL, ONH and 3D disk using RTVue 100. The means of each parameters were compared with ANOVA test. ROC curves were generated for different GCC and RNFL parameters. For both GCC and RNFL protocols the OR-logical disjunction (Boolean Logic Operator) was calculated. Areas under the ROC curves (AUC) of each parameter were compared ( Delong test). Results The AUCs for Average, Superior, Inferior RNFL were not significantly different (0.72, 0.71, 0.75 respectively): the largest AUC for RNFL parameters was that of RNFL OR (0.79). Average, Superior, Inferior, FLV % GCC (0.74, 0.71, 0.77, 0.76 respectively) were not significantly different from each other and from RNFL AUCs. The largest AUC was that of GLV% GCC (0.81) which is significantly higher than both RNFL and GCC parameters AUCs. Even for the GCC scan, the GCC OR AUC (0.78) was better than others parameters, exception for GLV%. Conclusion We found that GLV% had higher diagnostic accuracy than the simple average for the diagnosis of glaucoma: this must mean that, in some cases, pattern parameters are more sensitive or more specific. The computation of Boolean OR Operator have been found to boost diagnostic accuracy. In summary, analysis of GCC loss pattern further boosted diagnostic accuracy of RNFL measurements.

PURPOSE To evaluate and compare the diagnostic ability of Cirrus and Stratus optical coherence tomography (OCT) to detect localized retinal nerve fiber layer (RNFL) defects in patients with normal standard automated perimetry. METHODS This study included 55 eyes of 55 subjects with preperimetric localized RNFL defects and 55 normal control eyes of 55 age- and sex-matched subjects. Areas under the receiver operating characteristic curves (AUROCs) were calculated and compared. Based on the internal normative database from each device, the sensitivity and specificity for detecting preperimetric localized RNFL defects were calculated. RESULTS There was no statistically significant difference between the AUROCs for the best parameters from the Cirrus OCT (inferior thickness, AUROC = 0.728) and Stratus OCT (7 o'clock sector, AUROC = 0.760; P = 0.477). The sensitivity of the Cirrus OCT parameters ranged from 21.0% to 87.1% and that of the Stratus OCT parameters ranged from 4.8% to 30.7%, with the criterion of abnormal at the 5% level. Based on the normative database, the highest Cirrus OCT sensitivity was obtained with the deviation-from-normal map (sensitivity 87.1% and specificity 61.8%), and the highest Stratus OCT sensitivity was obtained with the TSNIT thickness graph (sensitivity 30.7% and specificity 85.5%). CONCLUSIONS There were no significant differences between the AUROCs for Cirrus and Stratus OCT, indicating that the two devices have similar diagnostic potentials in preperimetric glaucoma. After comparison with their normative databases, Cirrus OCT had generally higher sensitivities; however, this was largely at the cost of lower specificities than Stratus OCT.

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

Purpose To evaluate the correlation between GDx VCC parameters with global indexes of standard automated perimetry (SAP). Methods 417 eyes of 417 patients were included. They were divided into 60 normal, 218 ocular hypertensive, 68 preperimetric glaucoma, and 71 glaucoma. Correlation between GDx VCC parameters and global indexes of SAP (MD and PSD) was calculated in all groups. Results There was no significant correlation between GDx VCC and SAP between GDx and SAP in normal patients. Significant correlations were found for some parameters of GDx VCC and MD, being low for ocular hypertensive eyes and preperimetric glaucoma, and moderate-low for the glaucoma group. We only found significant correlations for a few parameters of GDx VCC and PSD in the glaucoma group, being the correlation coefficients low. Conclusion GDx VCC shows weak-moderate correlations with SAP. The correlations were higher for MD than PSD.