Peripapillary Vascular Density in Childhood Glaucoma: A Pilot Comparative Study with Age and Sex Matched Healthy Subjects.

PURPOSE: The aim of this study concerns the evaluation of peripapillary vessel indices in childhood glaucoma (CG) and healthy subjects. MATERIAL AND METHODS: In this prospective, unicenter, observational cross-sectional study, patients with CG and age and sex-matched healthy subjects were included. We compared retinal nerve fiber layer (RNFL) measurements in optical coherence tomography (OCT), peripapillary vessel density (PVD), and the flux index (FI) of the superficial vascular plexus from OCT angiography (OCT-A) between CG patients and control groups. RESULTS: We included 39 patients (68 eyes) with CG and 50 (95 eyes) healthy subjects. The peripapillary RNFL thickness, vessel density, and flux index were significantly lower in the CG group than in the control group. The mean PVD of CG patients was 0.52 ± 0.043%, compared with 0.55 ± 0.014%, p < 0.0001 in healthy subjects. The mean FI was 0.32 ± 0.054 versus 0.37 ± 0.028, p < 0.0001, in CG patients and healthy subjects, respectively. PVD and FI in the superior, inferior, and temporal sectors were significantly lower in CG. The peripapillary RNFL thickness showed a higher area under the ROC curve (AUROC) for discriminating healthy and CG eyes and was significantly different than the PVD (0.797, 95%CI 0.726-0.869; p < 0.0001 vs. 0.664, 95%CI 0.574-0.752; p 0.00037), p 0.012. CONCLUSIONS: PVD and FI show lower values in CG and correlate with RNFL thickness measurement but have lower diagnostic ability than RNFL thickness measurement. Our results reveal possible differences in the pathogenesis of microvascular compromise in childhood glaucoma patients.

Effect of Hypercholesterolemia, Systemic Arterial Hypertension and Diabetes Mellitus on Peripapillary and Macular Vessel Density on Superficial Vascular Plexus in Glaucoma.

BACKGROUND/AIMS: Vascular factors are involved in the development of glaucoma, including diseases such as hypercholesterolemia (HC), systemic arterial hypertension (SAH), and diabetes mellitus (DM). The aim of this study was to determine the effect of glaucoma disease on peripapillary vessel density (sPVD) and macular vessel density (sMVD) on the superficial vascular plexus, controlling differences on comorbidities such as SAH, DM and HC between glaucoma patients and normal subjects. METHODS: In this prospective, unicenter, observational cross-sectional study, sPVD and sMVD were measured in 155 glaucoma patients and 162 normal subjects. Differences between normal subjects and glaucoma patients' groups were analyzed. A linear regression model with 95% confidence and 80% statistical power was performed. RESULTS: Parameters with greater effect on sPVD were glaucoma diagnosis, gender, pseudophakia and DM. Glaucoma patients had a sPVD 1.2% lower than healthy subjects (Beta slope 1.228; 95%CI 0.798-1.659, p < 0.0001). Women presented 1.19% more sPVD than men (Beta slope 1.190; 95%CI 0.750-1.631, p < 0.0001), and phakic patients presented 1.7% more sPVD than men (Beta slope 1.795; 95%CI 1.311-2.280, p < 0.0001). Furthermore, DM patients had 0.9% lower sPVD than non-diabetic patients (Beta slope 0.925; 95%CI 0.293-1.558, p = 0.004). SAH and HC did not affect most of the sPVD parameters. Patients with SAH and HC showed 1.5% lower sMVD in the outer circle than subjects without those comorbidities (Beta slope 1.513; 95%CI 0.216-2.858, p = 0.021 and 1.549; 95%CI 0.240-2.858, p = 0.022 respectively. CONCLUSIONS: Glaucoma diagnosis, previous cataract surgery, age and gender seem to have greater influence than the presence of SAH, DM and HC on sPVD and sMVD, particularly sPVD.

Diagnostic validity of optic nerve head colorimetric assessment and optical coherence tomography angiography in patients with glaucoma.

BACKGROUND/AIMS: The aim of this study was to assess the optic nerve head (ONH) and macular vessel density with optical coherence tomography angiography (OCT-A) and the ONH haemoglobin (ONH Hb) amount with Laguna ONhE program in open-angle glaucoma (OAG) patients. METHODS: In this prospective observational cross-sectional study, 67 OAG patients and 41 healthy age-sex frequency matched subjects were examined with OCT-A and retinal photos. The circumpapillary (wcpVD), optic nerve head (iVD) and macular (wmVD) capillary vessel density of OCT-A and ONH colorimetric assessment to determine the ONH Hb amount using the Laguna ONhE program were evaluated. RESULTS: Significant differences between normal subjects and glaucoma patients in the wcpVD (22.18±3.42 vs 16.03±2.89%; p<0.001), iVD (18.31±5.56 vs 12.52±4.67%; p<0.001), wmVD (15.60±2.34 vs 13.34±2.32%; p<0.001) and amount of ONH Hb (71.10±1.67 vs 68.86±2.46%; p<0.001) and in the papillary cup (68.14±5.25 vs 64.77±5.08%; p=0.001) were found. The Laguna ONhE glaucoma discriminant function (GDF) index had a negative value in the OAG patients and normal values in healthy subjects (-18.76±13.31 vs 7.98±14.09; p<0.001). The area under the receiver operating characteristic (ROC) curve (AUROC) for discriminating between healthy and glaucomatous eyes was highest for wcpVD (0.93; 95% CI 0.86 to 0.97, p<0.0001), followed by GDF (0.92; 95% CI 0.86 to 0.97, p<0.0001), iVD (0.79; 95% CI 0.70 to 0.86; p<0.0001) and ONH Hb (0.78; 95% CI 0.69 to 0.85, p<0.0001). Pair wise comparisons showed that the AUROC of wcpVD (0.93) was not significantly different than GDF (0.92) (p=0.855). CONCLUSION: Laguna ONhE program and OCT-A have similar diagnostic validity in open-angle glaucoma patients.

Gender-related Influences on Superficial Papillary Microcirculation Measured with Optical Coherence Tomography Angiography in Patients with Glaucoma.

Purpose: To evaluate the optic nerve head (ONH), macular vessel density, and retinal nerve fiber layer (RNFL) thickness differences between the genders. Material and methods: In this prospective case-control cross-sectional study 111 healthy subjects and 130 primary open-angle glaucoma (OAG) patients were examined with optical coherence tomography angiography (OCT-A (RS-3000 Advance (Nidek, Gamagori, Japan))). The vessel density in the peripapillary and macular area as well as the RNFL thickness was evaluated. Results: Men appeared to have less RNFL thickness compared with women in early glaucomatous group, being significant at the whole circumpapillary retinal nerve fiber layer (cpRNFL) thickness and inferior and nasal quadrants: (cpRNFL) (71.01 ± 9.32 vs 77.64 ± 9.95 µm; P = .001), superior quadrant (89.10 ± 16.63 vs 92.97 ± 17.53 µm; P = .284), inferior quadrant (83.03 ± 19.17 vs 95.07 ± 21.70 µm; P = .006), temporal quadrant (57.11 ± 10.36 vs 61.78 ± 11.37 µm; P = .043), nasal quadrant (54.81 ± 11.42 vs 60.73 ± 11.62 µm; P = .016). Circumpapillary (wcpVD) and macular (wmVD) vessel density values were lower in men than women in the early stage OAG group, being wmVD significantly lower: wcpVD (15.53 ± 2.45% vs 16.81 ± 3.17%, P = .032) and wmVD values (12.51 ± 2.21 vs 13.63 ± 2.28%, P = .019), but not in the moderate OAG group (wcpVD 14.46 ± 2.20% vs 16.61 ± 3.10%, P = .056 and wmVD 12.61 ± 2.40% vs 12.74 ± 2.54%, P = .870). There were no significant differences between men and women for RNFL thickness and the vessel density parameters in normal group. Conclusion: Both, the thickness of the nerve fiber layer and peripapillary and macular vessel density are lower in men than in women with glaucoma, more markedly in early stage glaucomatous patients.

Influence of Axial Length on Intraocular Pressure Measurement With Three Tonometers in Childhood Glaucoma.

PURPOSE: To determine the agreement between intraocular pressure (IOP) measurements obtained using the handheld version of the Goldmann applanation (Perkins; Clement-Clarke, Haag-Streit, Harlow, United Kingdom), rebound Icare-Pro (Icare, Tiolat Oy, Helsinki, Finland), and Tonopen XL (Reichert Inc., Depew, NY) tonometers in children with childhood glaucoma and to identify factors that may affect those measurements. METHODS: Ninety-one eyes of 46 children with early-onset childhood glaucoma were included in this cross-sectional study in which IOP, ocular axial length, anterior chamber depth, lens thickness, vitreous length, and central corneal thickness measurements were obtained under general anesthesia. Agreement between tonometers was evaluated using intraclass correlation coefficients (ICCs) and the Bland-Altman method. The influence of ocular biometric parameters and central corneal thickness on IOP measurements was analyzed using multiple linear regression analysis. RESULTS: The mean age of the children in the current study was 29.1 months (range: 13 to 31 months). The Icare-Pro and Tonopen XL overestimated IOP measurements compared to the Perkins tonometer (Icare-Pro-Perkins mean IOP difference: 2.2 ± 3.4 mm Hg, P < .0001, 95% confidence interval [CI]: 1.5 to 2.9 vs Tonopen XL-Perkins mean IOP difference: 6.7 ± 7.1 mm Hg, P < .0001, 95% CI: 5.2 to 8.2). The Icare-Pro showed greater agreement with the Perkins tonometer than the Tonopen XL (ICC: 0.789, 95% CI: 0.697 to 0.856, P < .0001 vs 0.453, 95% CI: 0.272 to 0.603, P < .0001). Ocular axial length affected IOP measurements the most, finding increased impact on Tonopen XL (slope: 0.086, 95% CI: 0.013 to 0.16, P = .022 vs 0.997, 95% CI: 0.369 to 1.625, P = .002 vs 1.571, 95% CI: 0.541 to 2.602, P < .0001 for Perkins, Icare-Pro, and Tonopen XL IOP measurements, respectively). CONCLUSIONS: Ocular axial length affects IOP measured by the Perkins, Icare-Pro, and Tonopen XL devices in patients with childhood glaucoma. The Icare-Pro shows more agreement with the Perkins tonometer than the Tonopen XL; therefore, it seems to be a more suitable option for these patients. [J Pediatr Ophthalmol Strabismus. 2020;57(1):27-32.].

Icare-Pro Rebound Tonometer Versus Hand-held Applanation Tonometer for Pediatric Screening.

PURPOSE: To compare intraocular pressure (IOP) measurements obtained using the new rebound tonometer Icare-Pro (Icare, Tiolat Oy, Helsinki, Finland) and the hand-held version of the Goldmann applanation tonometer (Perkins; Clement Clarke, Haag-Streit, Harlow, United Kingdom) in healthy children during clinical practice. METHODS: In this prospective study, three IOP measurements were made using each tonometer in a single session, starting with the Icare-Pro. Participants were 173 non-anesthetized patients aged 1 to 16 years. Measurements were made in both eyes but only data for the right eye were entered in the analysis. Central corneal thickness, anterior chamber depth, and axial length were also measured in each patient. Data were compared by determining interclass correlation coefficients (ICCs) for each tonometer and representing the differences detected as Bland-Altman plots. RESULTS: Good linear correlation was observed between IOP readings obtained using the Perkins and Icare-Pro tonometers (r = 0.87, P < .001), although the Icare-Pro readings were slightly higher (mean IOP difference: 0.26 ± 1.58 mm Hg, P = .037). The 95% limits of agreement between the two methods were 2.8 to -3.4 mm Hg. The ICC was 0.857 (95% confidence interval: 0.810 to 0.893), indicating good agreement. For both tonometers, a low but significant correlation was detected between IOP and central corneal thickness or age. However, no correlation of IOP was found with axial length or anterior chamber depth. CONCLUSIONS: Pediatric IOP measurements determined using the new Icare-Pro rebound tonometer showed good correlation with those obtained using the hand-held Perkins applanation tonometer in a routine clinical examination with no need for general anesthesia. [J Pediatr Ophthalmol Strabismus. 2018;55(6):382-386.].

Tonometry after Intrastromal Corneal Ring Segments for Keratoconus.

SIGNIFICANCE: Reliable intraocular pressure (IOP) measurement after intrastromal corneal ring segments (ICRS) implantation is a challenge because of altered corneal morphology. In this study, IOP is measured with four tonometers, compared with Goldmann applanation tonometry (GAT) values and the influence of corneal parameters is established. PURPOSE: This study compares IOP measurements made using different tonometers in patients implanted with ICRS and assesses the effects of central corneal thickness (CCT), corneal curvature, and corneal astigmatism on the IOP measurements obtained. METHODS: In this cross-sectional study, IOP was measured using three different tonometers in 91 eyes of 91 patients with corneal ectasia implanted at least 6 months previously with ICRS. The tonometers tested were the TonoPen XL, Pascal dynamic contour tonometer (DCT), and iCare Pro rebound tonometer. GAT measurements were used as reference. Agreement among the IOPs provided by the different tonometers and the influence of corneal variables on the IOP measurements obtained were assessed using the Bland-Altman method, intraclass correlation coefficients, and multiple linear regression analysis. RESULTS: Mean IOP differences were GAT versus TonoPen XL -0.8 ± 3.07 mm Hg, GAT versus DCT -1.0 ± 3.26 mm Hg, and GAT versus iCare Pro 0.8 ± 2.92 mm Hg. Our multiple linear regression analysis identified CCT as a confounding factor affecting all the tonometer readings but DCT-IOP. CONCLUSIONS: In patients fitted with ICRS, IOP measurements made using the iCare Pro and TonoPen XL showed most agreement with GAT. Intraocular pressure measurements made by DCT were unaffected by corneal topographic factors though this procedure slightly overestimated GAT readings.

Measuring Intraocular Pressure in Patients With Keratoconus With and Without Intrastromal Corneal Ring Segments.

PURPOSE: To compare intraocular pressure (IOP) measurements made using 5 tonometers in keratoconic eyes with and without intrastromal corneal ring segments. METHODS AND PATIENTS: This was an observational case series study. A total of 147 eyes of 147 patients with keratoconus, 74 of which had undergone corneal ring segment placement, were prospectively evaluated. IOP was measured using the tonometers Tonopen XL, Pascal dynamic contour tonometer, iCare Pro, ocular response analyzer (ORA), and Goldmann applanation (GAT) in random order. The Bland-Altman method was used to examine interinstrument agreement. Effects on readings of central corneal thickness, corneal curvature, and corneal astigmatism were assessed by multivariate regression analysis. RESULTS: Smallest mean IOP differences with GAT measurements in eyes without and with ring segments, respectively, were detected for iCare Pro [0.2 (2.9) mm Hg and 0.4 (3.0) mm Hg, P=0.914] and greatest differences for ORA Goldmann-correlated IOP [5.8 (3.3) mm Hg and 6.0 (3.1) mm Hg, P=0.363]. Best agreement with GAT was shown by iCare Pro (ICC=0.829; 95% CI, 0.721-0.896) and worse agreement by ORA corneal-compensated IOP (ICC=-0.145; 95% CI, -0.826 to 0.283). All but the dynamic contour tonometer readings were influenced by central corneal thickness, yet these measurements were affected by the presence of ring segments (P=0.017) and corneal astigmatism (P=0.030). Corneal curvature only affected ORA Goldmann-correlated IOP (P=0.029). CONCLUSIONS: All 5 tonometers provided reliable IOP readings in the keratoconic eyes regardless of the presence of corneal ring segments. iCare Pro readings were most consistent with GAT, whereas ORA readings were least consistent with this reference standard.

Glaucoma diagnostic capacity of optic nerve head haemoglobin measures compared with spectral domain OCT and HRT III confocal tomography.

PURPOSE: The computer program laguna onhe determines optic nerve head haemoglobin (ONH Hb) on retinal photographs based on detecting colour differences. This study compares the diagnostic capacity of Laguna ONhE with that of spectral domain optical coherence tomography (OCT) and confocal tomography (HRT III). METHODS: In a prospective, observational, cross-sectional study, glaucomatous (n = 66) and healthy (n = 52) eyes were examined by Spectralis OCT, HRT III and Laguna ONhE. The following Laguna ONhE variables were determined: ONH Hb across the vertical disc diameter (8&20 Hb), estimated cup-disc ratio (C/D) and the glaucoma discriminant function (GDF), which combines the slope of Hb amount with the mean in 8&20 Hb. The three diagnostic methods were compared by calculating areas under ROC curves (AUCs). Correlations between variables were assessed through Spearman's rho coefficient. RESULTS: Areas under ROC curves (AUCs) were 0.785 (95% CI: 0.700-0.863) for GDF, 0.807 (95% CI: 0.730-0.883) for OCT retinal nerve fibre layer thickness (OCT-RNFL) and 0.714 (95% CI: 0.618-0.810) and 0.721 (95% CI: 0.628-0.815) for the HRT III variable GPS (glaucoma probability score) and vertical C/D ratio, respectively. Glaucoma discriminant function (GDF) was correlated with OCT-RNFL (0.587, p 0.001; 0.507, p 0.045; and -0.119, p 0.713 for mild, moderate and advanced glaucoma, respectively), mostly so with inferior OCT-RNFL (0.622; p < 0.001). Glaucoma discriminant function (GDF)-HRT III correlations were lower (rim area 0.471, p < 0.0001; rim/disc area 0.426, p < 0.0001; vertical C/D -0.413, p < 0.0001; GPS -0.408, p < 0.0001; rim volume 0.341, p < 0.0001). CONCLUSION: Similar diagnostic power was observed for Laguna ONhE, Spectralis OCT and HRT III.

Reproducibility of Optic Nerve Head Hemoglobin Measures.

PURPOSE: To evaluate intraobserver, interobserver, within-session and between-session reproducibility of the measurement of optic nerve head (ONH) hemoglobin levels by color analysis using Laguna ONhE [optic nerve hemoglobin (ONH Hb)] program. MATERIALS AND METHODS: This was an observational prospective study of 29 eyes (11 glaucomatous; 18 healthy eyes). Two examiners obtained 2 retinal photographs (Canon non-mydriatic retinal camera CD-DGi, Canon Inc.,Tokyo, Japan) in 2 testing sessions 3 weeks apart and analyzed the images using Laguna ONhE. The following parameters were quantified: ONH hemoglobin amounts across the whole disc (ONH Hb) and in the vertical disc diameter (8&20 Hb), cup-disc ratio (C/D), and the Glaucoma Discriminant Function (GDF). Agreement was illustrated using the Bland-Altman plots and reproducibility was assessed comparing the intraclass correlation coefficients (ICC). RESULTS: In session 1, examiner 1 found mean levels of ONH hemoglobin of 67.94±8.70% in healthy eyes and of 57.90±5.36% in glaucomatous eyes. Corresponding values for examiner 2 were 68.27±8.52% and 57.83±4.88%, respectively. ONH Hb and 8&20 Hb measurements were lower in glaucomatous eyes (P=0.002 and P=0.001 respectively). GDF was also more pathologic in glaucomatous group. C/D ratio estimation was greater in the glaucoma group (P=0.003). ONH Hb and 8&20 Hb showed the highest ICCs (all above 0.9). Variability was greater for GDF (ICC>0.8) and C/D ratio estimation (ICC>0.71). CONCLUSIONS: Measurement of ONH Hb levels using the Laguna ONhE program shows high reproducibility both in glaucomatous and nonglaucomatous ONHs.

Measuring intraocular pressure after intrastromal corneal ring segment implantation with rebound tonometry and Goldmann applanation tonometry.

PURPOSE: The aim of this study was to compare intraocular pressure (IOP) measurements in patients with ectatic corneas after intrastromal corneal ring segment (ICRS) implantation using the Rebound tonometers (RBTs) Icare and Icare Pro, compared with Goldmann applanation tonometry (GAT) and to assess the influence of central corneal thickness (CCT), corneal curvature (CC), and corneal astigmatism (CA) on IOP. METHODS: This prospective cross-sectional study consecutively included 60 eyes of 60 patients with corneal ectasia having ICRS for at least 6 months from January 2011 to December 2013. All subjects underwent GAT, Icare, and Icare Pro IOP measurements in a random order, and CCT, CC, and CA evaluation using a Pentacam. The Bland-Altman method and multivariate regression analysis logistic method were used to assess intertonometer agreement and the influence of corneal variables on IOP measurements. RESULTS: Icare significantly underestimated IOP compared with GAT [GAT - Icare 1.2 ± 3.0 mm Hg, P = 0.002 (95% confidence interval, 0.5-2.0)], whereas Icare Pro showed no statistical differences compared with GAT [GAT - Icare Pro 0.1 ± 3.1 mm Hg, P = 0.853 (95% confidence interval, -0.7 to 0.9)]. Both RBTs presented good concordance with GAT (intraclass coefficient correlation > 0.6). All tonometer measurements were influenced by CCT values and age (P < 0.05); the number of ICRS implanted did not influenced IOP measurement with any of the 3 tonometers. CONCLUSIONS: Both RBTs could be an alternative to GAT in patients with corneal ectasia and ICRS; however, Icare Pro shows greater accuracy.