The Importance of Signal Strength Index in Optical Coherence Tomography Angiography: A Study of Eyes with Pseudoexfoliation Syndrome.

Purpose: To evaluate the effect of the signal strength index (SSI) on a comparison of the vascular and structural OCT measurements between eyes with pseudoexfoliation syndrome (PXF) and healthy controls of Asian-Indian origin. Methods: In this cross-sectional study, 33 eyes of 33 PXF patients and 40 healthy eyes of 40 controls underwent OCT and OCT angiography (OCTA). Eyes with intraocular pressure (IOP) >21mmHg, glaucomatous disc changes, or any other ocular pathology were excluded. Peripapillary vessel density (VD) and retinal nerve fiber layer (RNFL) thickness were determined from the optic disc scans. Parafoveal VD and ganglion cell complex (GCC) thickness were measured from the macular scans. These parameters were compared between the groups using mixed effect models after adjusting for clinical confounders such as IOP, as well as SSI of the scans. Results: The 2 groups were demographically similar. Average RNFL (94µm vs 100µm, p = 0.01) and GCC (91µm vs 95µm, p = 0.03) were thinner in the PXF group compared to controls. The average peripapillary VD appeared lower in the PXF groups compared to controls (58.2% vs 58.8%, p = 0.04), but after adjusting for IOP and SSI, no difference was noted (p = 0.39). After accounting for confounders, parafoveal VD in the PXF group was significantly lower compared to controls (44.3% vs 46.8%, p = 0.008). Conclusion: Peripapillary RNFL thickness, parafoveal GCC thickness and parafoveal VD were decreased in eyes with PXF when compared to controls. VD measurements are associated with the SSI and, therefore, clinicians and researchers evaluating OCTA scans quantitatively must consider the SSI value during analysis and interpretation.

Prevalence of primary angle-closure disease in retinitis pigmentosa.

Purpose: To determine the prevalence of primary angle-closure disease (PACD) in patients with retinitis pigmentosa (RP). Methods: This was a retrospective review of the electronic medical records of all RP patients over the age of 10 years attending the Genetics Eye Clinic of a tertiary-care hospital during a 7-year period. Information regarding age, gender, vision, refraction, lens, intraocular pressure (IOP), type of RP, and inheritance pattern using pedigree charts for all patients were obtained. Patients with a shallow anterior chamber, high IOP, or glaucomatous optic discs were referred to the glaucoma department where they underwent additional IOP measurements, a gonioscopy, and disc evaluation by a glaucoma specialist. The prevalence of PACD was determined. Results: A total of 618 RP patients were examined during the study period, of which 95.1% had typical RP. The prevalence of primary angle-closure suspects was 2.9%, primary angle closure was 0.65%, and primary angle-closure glaucoma (PACG) was 2.27%. In contrast, the prevalence of primary open-angle glaucoma was 1.29%. The prevalence of PACG in those older than 40 years was 3.8% (95% confidence interval: 1.6-6.0). Conclusion: The prevalence of PACG in RP patients over 40 years was higher than that found in the general population of a similar age (3.8% vs. 0.8%). In our cohort of RP patients, 5.9% had PACD. Hence, gonioscopy is warranted in all RP patients to identify this condition and treat it appropriately.

Optical Coherence Tomography Angiography and Visual Field Progression in Primary Angle Closure Glaucoma.

PRECIS: Lower whole enface disc (coefficient: 0.02, P=0.03) and macular vessel densities (coefficient: 0.04, P=0.02) on optical coherence tomography angiography (OCTA) were significantly associated with faster rate of mean deviation (MD) decline. PURPOSE: To evaluate the association between OCTA features and prior visual field (VF) progression in primary angle closure glaucoma (PACG). METHODS: In a cross-sectional study, 46 eyes of 31 PACG patients with 5 reliable VF examinations performed over ≥3 years of follow-up underwent OCTA imaging. Effect of clinical (age, sex, number of antiglaucoma medications, mean, and SD of intraocular pressure during follow-up), optical coherence tomography (average retinal nerve fiber layer and ganglion cell complex thickness) and OCTA (whole enface vessel density of disc and macular scan, deep-layer microvascular dropout) parameters on the rate of MD change was evaluated using linear mixed models. RESULTS: Average (±SD) MD of the baseline VF was -7.4±7.3 dB, and rate of MD change was -0.32±0.29 dB/y. Whole enface vessel density of disc and macular scans was 39.5%±8.1% and 38.7%±4.4%, respectively. Microvascular dropout was noted in 33.3% of the eyes. Multivariate mixed models showed that lower whole enface disc (coefficient: 0.02, P=0.03) and macular vessel densities (coefficient: 0.04, P=0.02) were significantly associated with faster rate of MD decline. Other factors significantly associated with faster progression in multivariate models were older age (coefficient: -0.02, P<0.05) and the presence of systemic hypertension (coefficient: -0.37, P=0.01) and diabetes (coefficient: -0.28, P=0.05). CONCLUSIONS: Lower superficial vessel density measured using OCTA was significantly associated with faster VF progression in PACG. In these eyes, OCTA parameters can serve as biomarker suggestive of past VF progression.

Optical Coherence Tomography Angiography Vessel Density Measurements in Eyes With Primary Open-Angle Glaucoma and Disc Hemorrhage.

PURPOSE: To compare the vessel density measurements of optic nerve head, peripapillary and macular regions in severity-matched primary open-angle glaucoma (POAG) eyes with and without disc hemorrhage (DH) using optical coherence tomography (OCT) angiography, and to compare their diagnostic abilities with that of the rim area, retinal nerve fiber layer and the ganglion cell complex thickness measurements on OCT. METHODS: In a cross-sectional study, 66 eyes of 46 control subjects, 34 eyes of 33 POAG patients with DH (median mean deviation=-3.7 dB) and 63 eyes of 43 POAG patients without DH (median mean deviation=-3.8 dB) underwent imaging with spectral domain OCT. Area under receiver operating characteristic curves (AUC) and 5sensitivities at 90% specificity of vessel density and structural measurements in POAG eyes with DH were compared with those in POAG eyes without DH. RESULTS: Most of the vessel density and structural measurements were similar (P>0.05) in POAG eyes with and without DH. Whole enface vessel density of the disc scan and inferotemporal peripapillary vessel density showed the best AUC and sensitivity at 90% specificity both in POAG eyes with DH (0.82, 56% and 0.75, 59%) and without DH (0.91, 73% and 0.83, 67%). AUCs and sensitivities of vessel density and structural measurements of POAG eyes with and without DH were statistically similar (P>0.05). CONCLUSIONS: OCT angiography measured vessel densities and their diagnostic abilities in POAG eyes with and without DH were similar. This suggests that the cause of DH in POAG is unlikely to be vascular abnormality.

Vessel Density and Structural Measurements of Optical Coherence Tomography in Primary Angle Closure and Primary Angle Closure Glaucoma.

PURPOSE: To evaluate the vessel density measurements of the optic nerve head (ONH), peripapillary, and macular regions on optical coherence tomography (OCT) angiography in eyes with primary angle closure (PAC) and primary angle closure glaucoma (PACG), and to compare their diagnostic abilities with the ONH rim area, peripapillary retinal nerve fiber layer (RNFL) thickness, and the macular ganglion cell complex (GCC) thickness measurements on OCT in PACG. DESIGN: Cross-sectional study. METHODS: Seventy-seven eyes of 50 control subjects, 65 eyes of 45 patients with PACG, and 31 eyes of 22 PAC patients with a history of high intraocular pressure underwent imaging with OCT. Area under receiver operating characteristic curves (AUC) and sensitivities at fixed specificities of vessel densities were compared with structural measurements. RESULTS: All the vessel density and structural measurements were significantly lower (P < .05) in the PACG compared with the control group. Vessel densities in the PAC were similar (P > .05) to that of the controls; the superotemporal RNFL, however, was significantly thinner in the PAC group (127 µm vs 135 µm, P = .01). The AUC and sensitivity at 95% specificity of vessel densities within the ONH (0.76 and 42%) and macular region (0.69 and 18%) in PACG were significantly lower P < .001) than ONH rim area (0.90 and 77%) and GCC thickness (0.91 and 55%), respectively. AUC and sensitivity of peripapillary vessel density (0.85 and 53%) were similar (P = 0.25) to RNFL thickness (0.91 and 65%). CONCLUSIONS: These results suggest that structural changes in PACG occur earlier than the reduction in retinal vessel densities.

Relationship of Optic Nerve Structure and Function to Peripapillary Vessel Density Measurements of Optical Coherence Tomography Angiography in Glaucoma.

PURPOSE: To evaluate the sectoral and global structure-structure (vessel density-retinal nerve fiber layer thickness) and structure-function (vessel density-visual sensitivity loss) relationships of peripapillary vessel density measurements on optical coherence tomography angiography in primary open-angle glaucoma and to determine if fractional polynomial (FP) models characterize the relationships better than linear models. MATERIALS AND METHODS: In a cross-sectional study, structure-structure and structure-function relationships of peripapillary vessel densities were determined in 227 eyes of 143 subjects (63 control and 164 primary open-angle glaucoma eyes) who had undergone standard automated perimetry and optical coherence tomography testing within 6 months of each other, using linear and FP models. FP model evaluates the relationship between the dependent and the best-fitting fractional powers of the independent variable. Strength of relationship was reported as coefficient of determination (R). RESULTS: R values for structure-structure associations using linear models (0.53 for superotemporal sector, 0.61 for inferotemporal, and 0.53 for average measurements) were significantly less (P<0.05) than that determined using FP models (0.57, 0.65, and 0.55, respectively). R values for structure-function associations using linear models (0.35 for superotemporal vessel density-inferotemporal visual sensitivity loss, 0.49 for inferotemporal vessel density-superotemporal visual sensitivity loss, and 0.39 for average vessel density-average visual sensitivity loss) were significantly less than that determined using FP models (0.43, 0.58, and 0.47, respectively). CONCLUSIONS: The inferotemporal peripapillary vessel density showed the strongest association with the corresponding retinal nerve fiber layer thickness and visual sensitivity loss in the global and sectoral regions studied. The FP models were significantly better than linear models in describing these relationships.

A comparison of the diagnostic ability of vessel density and structural measurements of optical coherence tomography in primary open angle glaucoma.

PURPOSE: To compare the diagnostic abilities of vessel density measurements of the optic nerve head (ONH), peripapillary and macular regions on optical coherence tomography (OCT) angiography in eyes with primary open angle glaucoma (POAG) with that of the ONH rim area, peripapillary retinal nerve fiber layer (RNFL) thickness and the macular ganglion cell complex (GCC) thickness measurements. METHODS: In a cross sectional study, 78 eyes of 50 control subjects and 117 eyes of 67 POAG patients underwent vessel density and structural measurements with spectral domain OCT. POAG was diagnosed based on the masked evaluation of optic disc stereo photographs. Area under receiver operating characteristic curves (AUC) and sensitivities at fixed specificities of vessel densities in ONH, peripapillary and macular regions were compared with rim area, RNFL and GCC thickness. RESULTS: The AUC (sensitivity at 95% specificity) of average vessel densities within the ONH, peripapillary and macular region were 0.77 (31%), 0.85 (56%) and 0.70 (18%) respectively. The same of ONH rim area, average RNFL and GCC thickness were 0.94 (83%), 0.95 (72%) and 0.93 (62%) respectively. AUCs of vessel densities were significantly lower (p<0.05) than that of the corresponding structural measurements. Pre-treatment IOP (coefficient: 0.08) affected (p<0.05) the AUC of ONH vessel density but not of any other vessel density or structural measurements. CONCLUSIONS: Diagnostic abilities of ONH, peripapillary and the macular vessel densities in POAG were significantly lower than ONH rim area, peripapillary RNFL and macular GCC measurements respectively. At fixed levels of glaucoma severity, the diagnostic ability of the ONH vessel density was significantly greater in eyes with higher pre-treatment IOP.

Predicting the Magnitude of Functional and Structural Damage in Glaucoma From Monocular Pupillary Light Responses Using Automated Pupillography.

PURPOSE: To predict the magnitude of functional damage [mean deviation (MD) on visual field examination] and structural damage [retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness on spectral domain optical coherence tomography] in glaucoma from monocular pupillary light response measurements using automated pupillography. METHODS: In total, 59 subjects (118 eyes) with either a confirmed or suspected diagnosis of glaucoma underwent automated pupillography, along with visual fields and spectral domain optical coherence tomography examinations. Association between pupillary light response measurements of each eye [amplitude of constriction, latency of onset of constriction (Loc), latency of maximal constriction (Lmaxc), velocity of constriction and velocity of redilation] and corresponding MD, average RNFL, and average GCC measurements were evaluated using univariate and multivariate regression analysis after accounting for the multicollinearity. Goodness of fit of the multivariate models was evaluated using coefficient of determination (R). RESULTS: Multivariate regression models that contained Loc and Lmaxc showed the best association with MD (R of 0.30), average RNFL thickness (R=0.18) and average GCC thickness (R=0.26). The formula that best predicts the MD could be described as: MD=-14.06-0.15×Loc+0.06×Lmaxc. The formula that best predicts the average RNFL thickness could be described as: Average RNFL thickness=67.18-0.22×Loc+0.09×Lmaxc. CONCLUSIONS: Glaucomatous damage as estimated by MD, RNFL, and GCC thickness measurements were best predicted by the latency parameters (Loc and Lmaxc) of pupillography. Worsening of glaucomatous damage resulted in a delayed onset of pupillary constriction and a decreased Lmaxc.

Comparing the Performance of Compass Perimetry With Humphrey Field Analyzer in Eyes With Glaucoma.

PURPOSE: To evaluate the reliability indices [fixation losses, false negative response rates (FN) and false positive response rates] and threshold sensitivities obtained from glaucoma patients with a Compass perimeter and to compare the same with the Humphrey field analyzer (HFA). METHODS: In a cross-sectional study, 97 eyes of 58 subjects (64 glaucoma and 33 glaucoma suspect eyes) underwent visual field examination with Compass and HFA. Any test with a fixation losses, FN or FP of >20% was considered unreliable. Reliability indices and threshold sensitivities between the 2 instruments were compared and the agreement evaluated using Bland and Altman analysis. RESULTS: In total, 37 tests (38%) with Compass and 17 (18%) with HFA were unreliable. The number of unreliable tests due to high FN (>20%) was significantly more (P=0.005) with Compass (n=27) than HFA (n=3). The mean difference [95% limits of agreement (LoA)] in mean sensitivity between Compass and HFA in the 51 eyes with reliable Compass and HFA results was -0.7 dB (-5.6, 4.3 dB). The point-wise threshold sensitivities with Compass were lower than that with HFA in central and temporal but higher in the nasal field. The 95% LoA ranged from -8 to +5 dB at one of the central points to -20 to +20 dB at one of the peripheral points. CONCLUSIONS: The numbers of unreliable tests were higher with Compass compared with HFA. The LoA between Compass and HFA for point-wise threshold sensitivities as well as the global indices were wide, implying that the instruments cannot be used interchangeably.

Diagnostic ability of peripapillary vessel density measurements of optical coherence tomography angiography in primary open-angle and angle-closure glaucoma.

AIMS: To evaluate the diagnostic ability of peripapillary vessel density measurements on optical coherence tomography angiography (OCTA) in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), and to compare these with peripapillary retinal nerve fibre layer (RNFL) thickness measurements. METHODS: In a cross-sectional study, 48 eyes of 33 healthy control subjects, 63 eyes of 39 patients with POAG and 49 eyes of 32 patients with PACG underwent OCTA (RTVue-XR, Optovue, Fremont, California, USA) and RNFL imaging with spectral domain OCT. Diagnostic abilities of vessel density and RNFL parameters were evaluated using area under receiver operating characteristic curves (AUC) and sensitivities at fixed specificities. RESULTS: AUCs of peripapillary vessel density ranged between 0.48 for the temporal sector and 0.88 for the inferotemporal sector in POAG. The same in PACG ranged between 0.57 and 0.86. Sensitivities at 95% specificity ranged from 13% to 70% in POAG, and from 10% to 67% in PACG. AUCs of peripapillary RNFL thickness ranged between 0.51 for the temporal sector and 0.91 for the inferonasal sector in POAG. The same in PACG ranged between 0.61 and 0.87. Sensitivities at 95% specificity ranged from 8% to 68% in POAG, and from 2% to 67% in PACG. AUCs of all peripapillary vessel density measurements were comparable (p>0.05) to the corresponding RNFL thickness measurements in both POAG and PACG. CONCLUSIONS: Diagnostic ability of peripapillary vessel density parameters of OCTA, especially the inferotemporal sector measurement, was good in POAG and PACG. Diagnostic abilities of vessel density measurements were comparable to RNFL measurements in both POAG and PACG.

Predicting the intereye asymmetry in functional and structural damage in glaucoma using automated pupillography.

PURPOSE: To predict the intereye asymmetry in functional (mean deviation, MD on visual field, VF) and structural (retinal nerve fibre layer, RNFL and ganglion cell complex, GCC thickness on spectral domain optical coherence tomography, SDOCT) measurements in glaucoma using the automated pupillography parameters. METHODS: Fifty-nine subjects with a diagnosis of either glaucoma or glaucoma suspect underwent automated pupillography along with VF and SDOCT examinations. Association between pupillography and the absolute intereye difference in MD, RNFL and GCC measurements was evaluated using regression analysis after accounting for the multicollinearity. RESULTS: Univariate regression analysis showed statistically significant associations (p < 0.05) between multiple pupillography parameters and the intereye difference in MD, RNFL and GCC thickness measurements. Multivariate regression with less strongly correlated parameters identified intereye difference in amplitude change (Ac) per cent to be the parameter that best predicted the intereye asymmetry in MD (Intereye asymmetry in MD = 2.20 + 1.33*intereye difference in Ac per cent, R2  = 0.36), RNFL thickness (3.38 + 3.55*intereye difference in Ac per cent, R2  = 0.49) and GCC thickness (4.49 + 2.06* intereye difference in Ac per cent, R2  = 0.41). Ability of intereye Ac per cent difference to predict intereye asymmetry in MD, RNFL and GCC thickness was better in patients with angle closure disease (R2  = 0.38, 0.79, 0.66, respectively) compared to those with open angles (R2  = 0.25, 0.15, 0.16, respectively). CONCLUSIONS: Intereye asymmetry in MD, RNFL and GCC thickness measurements was best predicted by the intereye difference in Ac per cent on automated pupillography. The predicting ability was better in patients with angle closure compared to those with open angles.

Regional Comparisons of Optical Coherence Tomography Angiography Vessel Density in Primary Open-Angle Glaucoma.

PURPOSE: To compare the diagnostic abilities of the vessel densities in optic nerve head (ONH), peripapillary, and macular regions measured using optical coherence tomography angiography (OCTA) in eyes with primary open-angle glaucoma (POAG), and to evaluate the effect of glaucoma severity (based on the mean deviation, MD), optic disc size, and pretreatment intraocular pressure (IOP). DESIGN: Cross-sectional study. METHODS: Seventy-eight eyes of 53 control subjects and 64 eyes of 39 POAG patients underwent OCTA imaging. Area under receiver operating characteristic (ROC) curves (AUC) and sensitivities at fixed specificities of vessel densities in ONH, peripapillary, and macular regions were analyzed. ROC regression was used to evaluate the effect of covariates on the diagnostic abilities. RESULTS: The AUCs of ONH vessel densities ranged between 0.59 (superonasal sector) and 0.73 (average inside disc), peripapillary between 0.70 (nasal, superonasal and temporal) and 0.89 (inferotemporal), and macular between 0.56 (nasal) and 0.64 (temporal). AUC of the average peripapillary vessel density was significantly better than the average inside disc (P = .05) and macular (P = .005) measurement. MD showed a negative association with the AUCs of the vessel densities of all regions. Pretreatment IOP (coefficient: 0.09) showed a significant (P < .05) effect on the AUC of ONH vessel density. CONCLUSIONS: Diagnostic ability of the vessel density parameters of OCTA was only moderate. Macular and inside disc densities had significantly lower diagnostic abilities in POAG than the peripapillary density. Diagnostic abilities of vessel densities increased with increasing severity of glaucoma and that of ONH vessel density with higher pretreatment IOPs.