Yuri Fujino

How Many Visual Fields Are Required to Precisely Predict Future Test Results in Glaucoma Patients When Using Different Trend Analyses

PURPOSE To evaluate the minimum number of visual field (VF) tests required to precisely predict future VF results using ordinary least squares linear regression (OLSLR), quadratic regression, exponential regression, logistic regression, and M-estimator robust regression model. METHODS Series of 15 VFs (Humphrey Field Analyzer 24-2 SITA standard) were analyzed from 247 eyes of 155 open-angle glaucoma patients. Future point-wise (PW) VF results and mean VF sensitivities were predicted with varying numbers of VFs in each regression method. RESULTS In PW-OLSLR, as expected, the minimum absolute prediction error was obtained using the maximum number of VFs in the regression (14 VFs); mean absolute prediction error was equal to 2.4 ± 0.9 dB. Ten VFs were required to reach the 95% confidence interval (CI) of the minimum absolute prediction error. Prediction errors associated with the exponential and quadratic regression models were significantly larger than those from PW-OLSLR, whereas errors from logistic regression were not significantly smaller than those from PW-OLSLR; however, the absolute prediction error from the M-estimator robust regression model was significantly smaller than those associated with PW-OLSLR (P < 0.01, paired Wilcoxon test). Like PW-OLSLR, 10 VFs were needed to obtain the minimum absolute prediction error of mean VF sensitivity, but there were no significant differences in errors using the different regression methods. CONCLUSIONS Approximately 10 VFs, are needed to achieve an accurate prediction of PW VF sensitivity and mean sensitivity. Prediction error of PW VF sensitivity can be significantly minimized using the M-estimator robust regression model compared with conventional OLSLR.

Evaluation of Glaucoma Progression in Large-Scale Clinical Data: The Japanese Archive of Multicentral Databases in Glaucoma (JAMDIG).

PURPOSE To develop a large-scale real clinical database of glaucoma (Japanese Archive of Multicentral Databases in Glaucoma: JAMDIG) and to investigate the effect of treatment. METHODS The study included a total of 1348 eyes of 805 primary open-angle glaucoma patients with 10 visual fields (VFs) measured with 24-2 or 30-2 Humphrey Field Analyzer (HFA) and intraocular pressure (IOP) records in 10 institutes in Japan. Those with 10 reliable VFs were further identified (638 eyes of 417 patients). Mean total deviation (mTD) of the 52 test points in the 24-2 HFA VF was calculated, and the relationship between mTD progression rate and seven variables (age, mTD of baseline VF, average IOP, standard deviation (SD) of IOP, previous argon/selective laser trabeculoplasties (ALT/SLT), previous trabeculectomy, and previous trabeculotomy) was analyzed. RESULTS The mTD in the initial VF was -6.9 ± 6.2 dB and the mTD progression rate was -0.26 ± 0.46 dB/year. Mean IOP during the follow-up period was 13.5 ± 2.2 mm Hg. Age and SD of IOP were related to mTD progression rate. However, in eyes with average IOP below 15 and also 13 mm Hg, only age and baseline VF mTD were related to mTD progression rate. CONCLUSIONS Age and the degree of VF damage were related to future progression. Average IOP was not related to the progression rate; however, fluctuation of IOP was associated with faster progression, although this was not the case when average IOP was below 15 mm Hg.

Applying "Lasso" Regression to Predict Future Visual Field Progression in Glaucoma Patients.

PURPOSE We evaluated the usefulness of various regression models, including least absolute shrinkage and selection operator (Lasso) regression, to predict future visual field (VF) progression in glaucoma patients. METHODS Series of 10 VFs (Humphrey Field Analyzer 24-2 SITA-standard) from each of 513 eyes in 324 open-angle glaucoma patients, obtained in 4.9 ± 1.3 years (mean ± SD), were investigated. For each patient, the mean of all total deviation values (mTD) in the 10th VF was predicted using varying numbers of prior VFs (ranging from the first three VFs to all previous VFs) by applying ordinary least squares linear regression (OLSLR), M-estimator robust regression (M-robust), MM-estimator robust regression (MM-robust), skipped regression (Skipped), deepest regression (Deepest), and Lasso regression. Absolute prediction errors then were compared. RESULTS With OLSLR, prediction error varied between 5.7 ± 6.1 (using the first three VFs) and 1.2 ± 1.1 dB (using all nine previous VFs). Prediction accuracy was not significantly improved with M-robust, MM-robust, Skipped, or Deepest regression in almost all VF series; however, a significantly smaller prediction error was obtained with Lasso regression even with a small number of VFs (using first 3 VFs, 2.0 ± 2.2; using all nine previous VFs, 1.2 ± 1.1 dB). CONCLUSIONS Prediction errors using OLSLR are large when only a small number of VFs are included in the regression. Lasso regression offers much more accurate predictions, especially in short VF series.

Adjusting Circumpapillary Retinal Nerve Fiber Layer Profile Using Retinal Artery Position Improves the Structure–Function Relationship in Glaucoma

PURPOSE To investigate whether correcting the circumpapillary retinal nerve fiber layer (cpRNFL) thickness profile, using retinal artery position and papillomacular bundle tilt, can improve the structure-function relationship in glaucoma patients. METHODS Spectral-domain optical coherence tomography (SD-OCT) and visual field measurements were conducted in 142 eyes of 90 subjects with open angle glaucoma. The SD-OCT cpRNFL thickness profile was corrected for retinal artery position and/or papillomacular tilt in all twelve 30° sectors of the optic disc, and the structure-function relationship against corresponding 30° sectorial retinal sensitivity was investigated by using linear mixed model. RESULTS Applying a correction to the cpRNFL thickness profile for retinal artery position resulted in a stronger structure-function relationship in all 12 sectors of the optic disc. Furthermore, applying a further adjustment for papillomacular tilt resulted in a further improvement in 9 of 12 sectors. CONCLUSIONS Correcting cpRNFL profile, using the retinal artery position significantly strengthened the structure-function relationship. In most optic disc sectors, using the papillomacular bundle tilt improved cpRNFL thickness measurements.

Ultrasound biomicroscopic study of sclerotomy sites after implantation of sustained release drug devices.

Background/aims: To evaluate the potential of ultrasound biomicroscopy (UBM) as a tool to study the precise location and changes of sclerotomy sites of the eye with an intraocular drug delivery device. Methods: Eight eyes of six patients (13 sites) who received ganciclovir implants were examined by UBM. Examinations were performed 1–26 months (mean 12.8 months) postoperatively. Serial transverse and radial sections of the anterior ciliary body around the sclerotomy sites were obtained. Results: The ganciclovir implant contour was successfully viewed using an UBM with high reflectivity. Three implants were deviated anteriorly and they were very close to the ciliary body and the lens (anterior deviation), while four implants were deviated posteriorly and away from the lens (posterior deviation). The other six implants were located at the appropriate position as intended. A solitary homogeneous mass with a medium reflectivity around the suture tab was observed at 12 out of 13 sites in seven eyes. Thick membranes extending from sclerotomy sites to the ora serrata were found at two sites in two eyes. Conclusion: UBM is helpful in detecting abnormal manifestations around ganciclovir implants and is a valuable tool to assess the changes of the sclerotomy sites of the sustained released intraocular devices.

Asymmetric Patterns of Visual Field Defect in Primary Open-Angle and Primary Angle-Closure Glaucoma

Purpose To compare the hemifield asymmetry of visual field (VF) loss in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) across all severity levels. Methods A total of 522 eyes of 327 patients with POAG (mean age ± SD, 54.1 ± 12.4 years) and 375 eyes of 204 patients with PACG (67.3 ± 8.9 years) were included. Subjects meeting the definitions of POAG or PACG were included. Means of the total deviation (TD) values (Humphrey 24-2 VF) in the Glaucoma Hemifield Test (GHT) regions were calculated in early (≥ -6 dB), moderate (< -6 dB and ≥ -12 dB), and advanced (< -12 dB) stages of POAG and PACG eyes. Then the differences of the TD values between superior and inferior hemifield GHT regions of POAG and PACG eyes were calculated. Also, the relationship between the values of pattern SD (PSD) and mean TD (mTD) was compared between POAG and PACG. Results In POAG eyes in the early stage, three regions (central, paracentral, and peripheral) in the superior hemifield had greater loss than their inferior counterparts; in moderate and advanced stages, all GHT regions in the superior hemifield had greater loss than their inferior counterparts. In PACG eyes, siginificantly fewer regions in the superior hemifield were significantly worse than their inferior counterpart, compared with POAG: one region (central) in early stage, two regions (central and peripheral) in moderate stage, and one region (central) in advanced stage. POAG eyes had greater PSD values than PACG eyes for given mean of TD values. Conclusions In both POAG and PACG eyes, VF damage was more pronounced in superior hemifield than inferior hemifield; however, this tendency was more obvious in POAG eyes than in PACG eyes.

The relationship between retinal nerve fibre layer thickness profiles and CorvisST tonometry measured biomechanical properties in young healthy subjects

We previously reported that a shallow circumpapillary retinal nerve fiber layer (cpRNFL) peak angle as measured by optical coherence tomography (OCT) suggests the temporal retina is stretched around the optic disc from the papillo-macular bundle (Yamashita T et al. Investigative Ophthalmol Vis Sci 2013). The purpose of the current study was to investigate the relationship between CorvisST tonometry (CST) corneal measurements, axial length (AL) and the change in OCT-measured cpRNFL peak angle, in young healthy subjects. OCT and CST measurements were carried out in 97 eyes of 97 young healthy volunteers. The relationship between cpRNFL peak angle and 12 CST parameters, adjusted for AL, was investigated using linear modelling. The mean ± standard deviation cpRNFL peak angle of the 97 healthy volunteers was 130.6 ± 25.4 (range: 77.8 to 207.0) degrees. The optimal linear model to explain cpRNFL peak angle (chosen from 216 different models) included three CST variables related to the speed and size of energy absorption (namely, A1 time, A1 length and A2 time), in addition to AL. In eyes with longer AL and shorter energy absorption in CST measurement, temporal retina is stretched around the optic disc from the papillo-macular bundle, as suggested by a shallow cpRNFL peak angle.

The association between photoreceptor layer thickness measured by optical coherence tomography and visual sensitivity in glaucomatous eyes

Purpose To assess the thickness of the photoreceptor layer in the macular region in glaucomatous eyes. Method Humphrey 10–2 visual field (VF) testing was carried out and mean threshold (mTH) was calculated in 118 eyes from 118 patients with open angle glaucoma. Macular optical coherence tomography (OCT) measurements (RS 3000, Nidek Co.ltd., Aichi, Japan) were also carried out in all eyes. Thickness measurements were recorded in the outer segment and retinal pigment epithelium (OS+RPE), the nerve fiber layer (NFL), the ganglion cell layer and inner plexiform layer (GCL+IPL), the inner nuclear layer and outer plexiform layer (INL+OPL) and the outer nuclear layer and inner segment (ONL+IS). The relationship between mTH and the thickness of these five different layers was investigated. Additionally, the influence of OS+RPE on mTH was investigated using partial correlation eliminating the effect of other variables of NFL, GCL+IPL, INL+OPL, ONL+IS, age, gender and axial length. Results The thickness of the OS+RPE layer was significantly decreased with the decrease of mTH (coefficient = 0.63 p <0.001). Partial correlation analysis suggested OS+RPE thickness is significantly (coefficient = 0.31, p <0.001) related to mTH, independent from NFL, GCL+IPL, INL+OPL, ONL+IS, age, gender and axial length. Conclusions The thickness of the RPE+OS layer appears to be related to visual sensitivity in glaucoma.

Investigating the usefulness of a cluster-based trend analysis to detect visual field progression in patients with open-angle glaucoma

Background/aims To investigate the usefulness of the Octopus (Haag-Streit) EyeSuite’s cluster trend analysis in glaucoma. Methods Ten visual fields (VFs) with the Humphrey Field Analyzer (Carl Zeiss Meditec), spanning 7.7 years on average were obtained from 728 eyes of 475 primary open angle glaucoma patients. Mean total deviation (mTD) trend analysis and EyeSuite’s cluster trend analysis were performed on various series of VFs (from 1st to 10th: VF1-10 to 6th to 10th: VF6-10). The results of the cluster-based trend analysis, based on different lengths of VF series, were compared against mTD trend analysis. Result Cluster-based trend analysis and mTD trend analysis results were significantly associated in all clusters and with all lengths of VF series. Between 21.2% and 45.9% (depending on VF series length and location) of clusters were deemed to progress when the mTD trend analysis suggested no progression. On the other hand, 4.8% of eyes were observed to progress using the mTD trend analysis when cluster trend analysis suggested no progression in any two (or more) clusters. Conclusion Whole field trend analysis can miss local VF progression. Cluster trend analysis appears as robust as mTD trend analysis and useful to assess both sectorial and whole field progression. Cluster-based trend analyses, in particular the definition of two or more progressing cluster, may help clinicians to detect glaucomatous progression in a timelier manner than using a whole field trend analysis, without significantly compromising specificity.

Effects of ocular and systemic factors on the progression of glaucomatous visual field damage in various sectors

Background/aim To investigate the effects of ocular and systemic risk factors for glaucomatous progression in different sectors of the visual field (VF). Method 409 eyes from 268 patients with 10 reliable VFs from the Japanese Archive of Multicentral Databases in Glaucoma (JAMDIG) were investigated. VFs were divided into six sectors (mean total deviation (mTD)s20+, mTDs10–20 and mTDs0–10, >20°, 10–20° and <10° in the superior hemifield, respectively; and mTDi20+, mTDi10–20 and mTDi0–10, >20°, 10–20° and <10° in the inferior hemifield, respectively). The relationship between sectorial progression rate and eight variables (age, mTD at baseline VF, average intraocular pressure (IOP), SD of IOP, systemic hypertension, migraine, family history of glaucoma and smoking status) was investigated. Result The mTD progression rate was −0.21 dB/year. Older age was related to progression of mTDs20+, mTDs10–20, mTDi20+ and mTDi10–20. Mean IOP was not related to progression in any VF sector; however, a larger SD of IOP was related to progression of mTDs20+, mTDi0–10, mTDi10–20 and mTDi20+. Smoking status was related to progression in all inferior VF sectors (mTDi0–10, mTDi10–20 and mTDi20+). Conclusions Smoking status is related to glaucomatous VF progression in all sectors of the inferior hemifield.