Predicting the Extent of Damage in the Humphrey Field Analyzer 24-2 Visual Fields Using 10-2 Test Results in Patients With Advanced Glaucoma.

Purpose: To predict Humphrey Field Analyzer 24-2 test (HFA 24-2) results using 10-2 results. Methods: A total of 175 advanced glaucoma eyes (175 patients) with HFA 24-2 mean deviation (MD24-2) of < -20 dB were prospectively followed up for five years using HFA 10-2 and 24-2 (twice and once in a year, respectively). Using all the HFA 24-2 and 10-2 test result pairs measured within three months (350 pairs from 85 eyes, training dataset), a formula to predict HFA 24-2 result using HFA 10-2 results was constructed using least absolute shrinkage and selection operator regression (LASSO). Using 90 different eyes (testing dataset), the absolute differences between the actual and LASSO-predicted MD24-2 and that between the slopes calculated using five actual and LASSO-predicted MD24-2 values, were adopted as the prediction error. Similar analyses were performed for the mean total deviation values (mTD) of the superior (or inferior) hemifield [hemi-mTDsup.24-2(-hemi-mTDinf.24-2)]. Results: The prediction error for the LASSO-predicted MD24-2 and its slope were 2.98 (standard deviation [SD] = 1.90) dB and 0.32 (0.33) dB/yr, respectively. The LASSO-predicted hemi-mTDsup.24-2 (hemi-mTDinf.24-2), and its slope were 3.02 (2.89) and 3.76 (2.72) dB, and 0.37 (0.41) and 0.44 (0.38) dB/year, respectively. These prediction errors were within two times SD of repeatability of the simulated stable HFA 24-2 VF parameter series. Conclusions: HFA 24-2 results could be predicted using the paired HFA 10-2 results with reasonable accuracy using LASSO in patients with advanced glaucoma. Translational Relevance: It is useful to predict HFA24-2 test from HFA10-2 test, when the former is not available, in advanced glaucoma.

Identifying central 10° visual subfield associated with future worsening of visual acuity in eyes with advanced glaucoma.

BACKGROUND/AIMS: To determine a cluster of test points: visual subfield (VSF) of Humphrey Field Analyzer 10-2 test (HFA 10-2) of which baseline sensitivities were associated with future worsening of visual acuity (VA) in eyes with advanced glaucoma. METHODS: A total of 175 advanced glaucoma eyes of 175 advanced glaucoma patients with well controlled intraocular pressure (IOP), a mean deviation of the Humphrey Field Analyzer 24-2 (HFA 24-2) test ≤ -20 decibels and best corrected VA ≥20/40, were included. At baseline, HFA 24-2 and HFA 10-2 tests were performed along with VA measurements. All patients underwent prospective follow-up of 5 years, and VA was measured every 6 months. The Cox proportional hazards model was used to identify visual field sensitivities associated with deterioration of VA and also blindness. RESULTS: Deterioration of VA and blindness were observed in 15.4% and 3.4% of the eyes, respectively. More negative total deviation (TD) values in the temporal papillomacular bundle VSF were significantly associated with deterioration in VA. Averages of the TD values in this area of the HFA 10-2 test had the most predictive power of future VA deterioration (OR: 0.92, p<0.001). A very similar tendency was observed for blindness. CONCLUSION: In advanced glaucoma eyes with well-controlled IOP, careful attention is needed when the mean TD values in the temporal papillomacular bundle VSF, measured with a HFA 10-2 test is deteriorated. TD values of this VSF indicate higher risks for future deterioration of VA and also blindness.

Factors Threatening Central Visual Function of Patients with Advanced Glaucoma: A Prospective Longitudinal Observational Study.

PURPOSE: To identify risk factors for further deterioration of central visual function in advanced glaucoma eyes. DESIGN: Prospective, observational 5-year study. PARTICIPANTS: Advanced glaucoma patients with well-controlled intraocular pressure (IOP), mean deviation (MD) of the Humphrey Field Analyzer (HFA) 24-2 program ≤-20 dB and best-corrected visual acuity (BCVA) of 20/40. METHODS: The HFA 10-2 test and BCVA examination were performed every 6 months, and the HFA 24-2 test was performed every 12 months for 5 years. The Cox proportional hazards model was used to identify risk factors for deterioration of HFA 10-2 and 24-2 results and BCVA. MAIN OUTCOME MEASURES: Deterioration of HFA 10-2 results was defined by the presence of the same ≥3 points with negative total deviation slope ≤-1 dB/year at P < 0.01 on ≥3 consecutive tests, deterioration of HFA 24-2 results by an increase ≥2 in the Advanced Glaucoma Intervention Study score on ≥2 consecutive tests, and deterioration of BCVA by an increase of ≥0.2 logarithm of the minimum angle of resolution (logMAR) on ≥2 consecutive tests. RESULTS: A total of 175 eyes of 175 patients (mean age, 64.1 years; mean baseline IOP, 13.2 mmHg; mean BCVA, 0.02 logMAR; mean HFA 24-2 and 10-2 MD, -25.9 and -22.9 dB, respectively) were included. The probabilities of deterioration in HFA 10-2 and 24-2 results and BCVA were 0.269 ± 0.043 (standard error), 0.173 ± 0.031, and 0.194 ± 0.033, respectively, at 5 years. Lower BCVA at baseline (P = 0.012) was associated significantly with further deterioration of HFA 10-2 results. Better HFA 24-2 MD (P < 0.001) and use of systemic antihypertensive agents (P = 0.009) were associated significantly with further deterioration of HFA 24-2 results, and a greater ß-peripapillary atrophy area-to-disc area ratio (P < 0.001), use of systemic antihypertensive agents (P = 0.025), and lower BCVA (P = 0.042) were associated significantly with further deterioration of BCVA, respectively. CONCLUSIONS: In advanced glaucoma eyes with well-controlled IOP, BCVA, ß-peripapillary atrophy area-to-disc area ratio, and use of systemic antihypertensive agents were significant prognostic factors for further deterioration of central visual function.

Evaluation of the relationship between glaucomatous disc subtypes and occurrence of disc hemorrhage and glaucoma progression in open angle glaucoma.

To compare the occurrence of disc hemorrhages (DH) and glaucoma progression in open-angle glaucoma (OAG) patients with different glaucomatous disc types. Prospective, hospital-based, observational cohort study. OAG patients examined between 2000 and 2005, whose discs were classified as typical myopic glaucomatous (MG), generalized enlargement of cup (GE), or focal glaucomatous (FG) disc type were included and followed for 5 years. The first occurrence of DH during follow-up was analyzed using Kaplan-Meier analysis and difference in DH occurrence based on glaucomatous disc type using the Cox proportional-hazards model to adjust for effects of confounding factors. For inter-group comparison of glaucoma progression, the change rate of the mean deviation, Collaborative Initial Glaucoma Treatment Study scores, and fundus photographs were used. Thirty-nine patients with MG-, 18 with FG-, and 17 with GE-disc types were included. No significant inter-group difference was seen in the rate of glaucoma progression. The five-year probability of DH occurrence was much lower with MG- than with FG- or GE-disc types (P < 0.0220). The central corneal thickness (P = 0.0024) and mean intraocular pressure and its variations (P = 0.0450, 0.0219) contributed to DH occurrence. The MG-disc type demonstrated a much lower DH occurrence during follow-up than other disc types.

Predicting Humphrey 10-2 visual field from 24-2 visual field in eyes with advanced glaucoma.

AIMS: To predict Humphrey Field Analyzer Central 10-2 Swedish Interactive Threshold Algorithm-Standard test (HFA 10-2) results (Carl Zeiss Meditec, San Leandro, CA) from HFA 24-2 results of the same eyes with advanced glaucoma. METHODS: Training and testing HFA 24-2 and 10-2 data sets, respectively, consisted of 175 eyes (175 patients) and 44 eyes (44 patients) with open advanced glaucoma (mean deviation of HFA 24-2 ≤-20 dB). Using the training data set, the 68 total deviation (TD) values of the HFA 10-2 test points were predicted from those of the innermost 16 HFA 24-2 test points in the same eye, using image processing or various machine learning methods including bilinear interpolation (IP) as a standard for comparison. The absolute prediction error (PredError) was calculated by applying each method to the testing data set. RESULTS: The mean (SD) test-retest variability of the HFA 10-2 results in the testing data set was 2.1±1.0 dB, while the IP method yielded a PredError of 5.0±1.7 dB. Among the methods tested, support vector regression (SVR) provided a smallest PredError (4.0±1.5 dB). SVR predicted retinal sensitivity at HFA 10-2 test points in the preserved 'central isle' of advanced glaucoma from HFA 24-2 results of the same eye within an error range of about 25%, while error range was approximately twice of the test-retest variability. CONCLUSION: Applying SVR to HFA 24-2 results allowed us to predict TD values at HFA 10-2 test points of the same eye with advanced glaucoma with an error range of about 25%.

Relationship between Vision-Related Quality of Life and Central 10° of the Binocular Integrated Visual Field in Advanced Glaucoma.

To investigate the relationships between sensitivity loss in various subfields of the central 10° of the binocular integrated visual field (IVF) and vision-related quality of life (VRQoL) in 172 patients with advanced glaucoma. Using the Random Forest algorithm, which controls for inter-correlations among various subfields of the IVF, we analysed the relationships among the Rasch analysis-derived person ability index (RADPAI), age, best-corrected visual acuity (BCVA), mean total deviations (mTDs) of eight quadrant subfields in the IVF measured with the Humphrey Field Analyzer (HFA) 10-2 program (10-2 IVF), and mTDs of the upper/lower hemifields in the IVF measured with the HFA 24-2 program (24-2 IVF). Significant contributors to RADPAIs were as follows: the inner and outer lower-right quadrants of the 10-2 IVF contributed to the dining and total tasks; the lower-left quadrant of the 10-2 IVF contributed to the walking, going out and total tasks; the lower hemifield of the 24-2 IVF contributed to the walking, going out, dining, miscellaneous and total tasks; and BCVA contributed more to the letter, sentence, dressing and miscellaneous tasks than to others. The impact of damage in different 10-2 IVF subfields differed significantly across daily tasks in patients with advanced glaucoma.

Effects of Brinzolamide, a Topical Carbonic Anhydrase Inhibitor, on Corneal Endothelial Cells.

INTRODUCTION: This clinical study aimed to investigate the effect of brinzolamide, a topical carbonic anhydrase inhibitor, on corneal endothelial cells (CECs) in patients with glaucoma using a follow-up clinical study design. METHODS: Patients with primary open-angle glaucoma or ocular hypertension were administrated an ophthalmic solution of either latanoprost alone (LT) as a control (n = 18) or latanoprost plus brinzolamide (LT + BR; n = 16). CECs were examined at baseline and at 4, 12, 24, and 48 weeks in 18 and 16 eyes of the LT and LT + BR groups, respectively, using a non-contact specular microscope. CECs were evaluated by parameters, including cell density (CD), coefficient of variation (CV) in cell size, and percentage hexagonality (Hex). RESULTS: Compared with the baseline intraocular pressure (IOP), the mean IOP in the LT group was significantly reduced at 12 and 24 weeks, whereas that in the LT + BR group was significantly reduced at all time points (P < 0.01). The mean CD, CV, and Hex at baseline were not significantly different between the two groups. No significant time-course changes in CD, CV, or Hex were observed in either group. At 48 weeks, there was no significant difference in the mean CD, CV, or Hex between the two groups. CONCLUSION: Patients treated with LT + BR showed significant IOP reduction. However, the use of brinzolamide in addition to latanoprost had no influence on CECs during the one-year follow-up period.

[Effects of optic disc size on progression of visual field defects in normal-tension glaucoma].

PURPOSE: To investigate the influence of optic disc area on the progression of visual field (VF) defects in normal-tension glaucoma (NTG). We evaluated the correlation between the right-left differences of the progression of VF defects and those of the intraocular pressure and the ocular anatomical factors. METHODS: Thirty two eyes of 16 NTG patients with a significant difference between the left and right optic disc area, were followed up for more than 5 years after diurnal variation analyzed with Heidelberg Retina Tomograph (HRT), and without myopic disc shape. The left and right eyes of the patients were allocated to two groups, a group with a relatively smaller eye disc and a group with relatively larger eye disc. They were studied regarding the probability of VF stability using the Kaplan-Meier life-table analysis. In addition, a comparison of clinical factors was evaluated between the two groups (Mann-Whitney U test). RESULTS: The probability of VF stability at the 107-month follow-up was 60 +/- 13% (mean +/- SE)in patients with small disc area, and 25 +/- 11% in patients with large disc area. Optic disc area was found to have significant influence on the progression of VF defects (p = 0.022, log-rank test). In clinical factors, no statistically significant difference except disc area was found between the two groups. CONCLUSIONS: These findings suggest that optic disc area is associated with the progression of VF defects in patients with NTG.

A case of 25 gauge vitrectomy for malignant glaucoma with microphthalmos.

UNLABELLED: We report the first case report of pars plana lensectomy (PPL) and pars plana vitrectomy using a 25 gauge vitrectomy system for microphthalmos. RESULTS: A 45-year-old woman reported repeated pain in her left eye, despite the use of medications. Ultrasound biomicroscopy revealed a narrow angle and thickened sclera. The lens and the iris showed anterior displacement with a flattening of the ciliary body. The axial length was 15.16 mm in the right eye and 15.04 mm in the left eye. She was diagnosed with a malignant glaucoma with microphthalmos. The patient underwent PPL and pars plana vitrectomy, using a 25 gauge vitrectomy system. The intraocular pressure was well controlled after surgery without medication. CONCLUSION: We considered the PPL and 25 gauge vitrectomy effective in microphthalmos when performed safely.

Optic disc size and progression of visual field damage in patients with normal-tension glaucoma.

PURPOSE: Our goal was to evaluate the influence of optic disc size on the progression of visual field damage in patients with normal-tension glaucoma (NTG). SUBJECTS AND METHODS: Eighty-two eyes of 82 NTG patients who had been receiving topical antiglaucoma medications and followed-up for more than 4 years were enrolled in this study. The patients were allocated to two groups, according to the mean size of their optic discs. The data were analyzed using regression analysis, based on the Cox proportional hazard model. RESULTS: The probability of visual field stability was significantly lower in eyes with large discs than in those with small discs (log rank test, P = 0.007). Progression of visual field damage was significantly associated with the optic disc area (hazard ratio [HR]: 1.812, P = 0.018), occurrence of disc hemorrhage (HR: 2.116, P = 0.028), and intraocular pressure reduction ratio (HR: 0.957, P = 0.014). CONCLUSION: The optic disc area correlates with progression of visual field damage in patients with NTG.

Superior segmental optic nerve hypoplasia accompanied by progressive normal-tension glaucoma.

This is the first case report of a superior segmental optic hypoplasia (SSOH) combined with normal-tension glaucoma accompanied by a progressive glaucomatous visual field defect. A 40-year-old man, incidentally diagnosed as having bilateral SSOH, had disc hemorrhage associated with expansion of the width of a retinal nerve fiber layer defect and deterioration of a visual field defect in the right eye during the follow-up period. His left eye showed a stable visual field. The diurnal variation in intraocular pressure (IOP) showed a higher mean IOP in his right eye compared with his left eye, although both IOPs remained under 21 mmHg.

Effect of trabeculectomy on retrobulbar circulation and visual field progression in patients with primary open-angle glaucoma.

BACKGROUND: The purpose of this study was to investigate the relationship between retrobulbar circulation and visual field change in eyes with primary open-angle glaucoma following unilateral trabeculectomy. METHODS: Twenty-one patients with primary open-angle glaucoma were prospectively enrolled. Retrobulbar circulation was evaluated using color Doppler imaging. The peak systolic velocity, end-diastolic velocity, and resistive index were evaluated in the central retinal artery, temporal site of the short posterior ciliary artery (t-SPCA), and nasal site of the short posterior ciliary artery (n-SPCA). Visual field examinations were performed using a Humphrey visual field analyzer before surgery and trimonthly for 12 months postoperatively. RESULTS: In the operative eyes, the end-diastolic velocity was significantly increased in the central retinal artery (P = 0.005, analysis of variance), t-SPCA (P = 0.005), and n-SPCA (P = 0.027). The resistive index was significantly decreased in the central retinal artery (P = 0.003), t-SPCA (P = 0.000), and n-SPCA (P = 0.010) postoperatively compared with preoperatively. The nonoperative contralateral eyes did not show a significant change in end-diastolic velocity or resistive index for either the SPCA or central retinal artery. The mean deviation slope in the operative eyes (-0.26 ± 0.64 dB/year) was significantly slower than that in the nonoperative eyes (-0.65 ± 0.70 dB/year; P = 0.047, Mann-Whitney U test). CONCLUSION: These results suggest that trabeculectomy improves the retrobulbar circulation and prevents the progression of visual field changes in patients with primary open-angle glaucoma.

Risk factors for progression of normal-tension glaucoma under ß-blocker monotherapy.

PURPOSE: To prospectively study prognostic factors for normal-tension glaucoma (NTG) under treatment with topical ß-blocker. METHODS: One hundred and forty-six eyes of 146 patients with NTG with a mean untreated intraocular pressure (IOP) of 14 mmHg, mild to moderate visual field damage and mean spherical equivalent refraction of -3.5 (-8.0 to +2.0) dioptre were randomized to topical nipradilol or timolol and followed for 3 years. The Humphrey full threshold 30-2 visual field test was performed every 6 months, and optic disc photographs were obtained every 12 months. Progression was defined as visual field progression, optic disc and/or peripapillary nerve fibre layer change, and factors relating to progression were evaluated using Cox proportional hazards models. RESULTS: IOP decreased by 1.0 mmHg over the 3-year period, during which 35% showed progression according to the aforementioned criteria. Optic disc haemorrhage (hazard ratio [HR] 4.00, p < 0.001) and less extent of myopia (per dioptre, HR 1.15, p = 0.013) were significant risk factors. When progression was defined by visual field progression only, less extent of myopia was again a significant risk factor (HR 1.17, p = 0.038). CONCLUSION: Beside optic disc haemorrhage, less extent of myopia was a risk factor for progression in the current NTG population where most patients were mildly myopic and IOP during follow-up averaged 13.2 mmHg under topical ß-blocker.

[Phase III clinical trial of brimonidine in patients with primary open-angle glaucoma and ocular hypertension--comparison of the effects of brimonidine monotherapy versus timolol monotherapy, or combination brimonidine/prostaglandins therapy versus combination placebo/prostaglandins therapy].

OBJECTIVE: To compare the intraocular pressure (IOP)-lowering effect and safety of topical brimonidine to that of timolol, and to study the additive effect of topical brimonidine to topical prostaglandin (PG) analogues in 475 patients with either ocular hypertension or primary open angle glaucoma. METHODS: The primary endpoint was the mean IOP change from the baseline at 0 and 2 hours at week 4. RESULTS: The mean changes were -4.7 +/- 2.1 (S. D.) in the timolol and -4.0 +/- 2.0 mmHg in the brimonidine group (p = 0.0138). The 95% confidence interval of the inter-group difference was greater than the pre-determined criterion of non-inferiority of brimonidine to timolol. When added to PG analogues, the IOP-lowering effect of brimonidine (-2.9 +/- 1.8 mmHg) was greater than that of the placebo (-2.1 +/- 1.8 mmHg) (p = 0.0010). No appreciable adverse side effects were encountered. CONCLUSION: Topical brimonidine showed an additive IOP-lowering effect to topical PG analogues, although its IOP-lowering effect was inferior to topical timolol as monotherapy.

[Investigation of the correlation between the right-left differences of visual field defects and the right-left differences of ocular anatomical factors in patients with normal-tension glaucoma].

PURPOSE: To investigate the effects of optic disc area to visual field (VF) defects of normal-tension glaucoma (NTG), the correlation between the right-left differences of VF defects and those of diurnal variations of intraocular pressure and the ocular anatomical factors were evaluated in patients with NTG. METHODS: One hundred eighteen eyes of 59 NTG patients with the right-left difference value of mean deviation (MD) of between 2 dB and 12 dB obtained with Humphrey field analyzer program 30-2 were enrolled in the study. The correlation between the right-left differences of MD values and those of refraction, axial length, central cornea thickness, diurnal variation of intraocular pressure, and disc area measured with Heidelberg Retina Tomograph were evaluated by multiple regression analysis. RESULTS: The multiple correlation coefficient was 0.520, and the coefficient of determination was 0.271. The right-left differences of axial length (p = 0.041) and disc area(p = 0.002) were judged to be the statistically significant factors correlated with those of VF defects. CONCLUSIONS: These results suggest that the right-left differences of axial length and disc area are associated with the right-left differences of VF defects in patients with NTG.

Visual field loss in patients with normal-tension glaucoma under topical nipradilol or timolol: subgroup and subfield analyses of the nipradilol-timolol study.

PURPOSE: To estimate the deterioration rates of visual field loss in Japanese normal-tension glaucoma (NTG) patients under either topical nipradilol or timolol, and to explore intergroup differences in the treatment results. METHODS: A total of 146 NTG patients with mild to moderate damage were randomized to either nipradilol or timolol and followed for 3 years with a periodic comprehensive ophthalmological visual field examination (30-2 Humphrey perimeter program) every 6 months (the Nipradilol-Timolol Study). The time course of mean deviation (MD), the average total deviation (TD(mean)) in four subfields, and the corrected pattern standard deviation (CPSD) were compared between the two groups using regression analysis with a linear mixed effect model. RESULTS: The estimated slope for MD (dB/year) was -0.03 in the nipradilol and -0.05 in the timolol group (P > 0.4). In both groups, TD(mean) in the superior-central subfield and CPSD showed significant changes (-0.3 and 0.2-0.3, P

[Study on relationship between control of intraocular pressure and systemic risk factor for visual field progression in normal-tension glaucoma].

PURPOSE: To study the relationship between the reduction of intraocular pressure (IOP) and visual field (VF) damage in normal-tension glaucoma (NTG) patients with or without systemic risk factors. METHODS: Ninety-two eyes of 92 patients with NTG were enrolled in this study. All patients were followed up for more than 2 years of taking topical antiglaucoma medications. Personal history regarding migraine, diabetes mellitus, hypertension, cerebrovascular disease, cardiovascular disease, Raynaud's phenomenon, arrhythmia, and family history of glaucoma were collected from the medical records. The survival data were analyzed using regression analysis based on the Cox proportional hazards model. The relationship between the presence of each systemic factor and the effect of reduction of VF progression were evaluated using the life table analysis. RESULTS: The progression of VF damage was significantly associated with IOP (p = 0.020). The eyes with larger IOP reduction showed significantly less VF progression than eyes with smaller IOP reduction both in patients with and without systemic diseases (with systemic diseases p = 0.027, without systemic diseases p = 0.025) and a family history of glaucoma (p = 0.019). In patients with a family history of glaucoma, the rate of VF progression did not show statistically differences between the eyes with larger IOP reduction and those with smaller IOP reduction. CONCLUSIONS: IOP reduction is beneficial in reducing the risk of VF progression regardless of the presence of systemic risk factors in patients with NTG.