Keiji Yoshikawa

Normal tension glaucoma: The value of predictive tests

Abstract. Fifty‐four normal tension glaucoma cases were studied to determine the value of several clinical tests for predicting the progression of the disease. Outflow facility, intraocular pressure (IOP) increase after water drinking, and diurnal changes in IOP were studied. Progression was determined on the basis of changes in visual sensitivity as measured on the Octopus 201. A minimum of four examinations of the central 30 degrees were conducted over a 3‐ to 7‐year period. Progression of visual field defects was seen in 38.5% of eyes that had demonstrated some degree of abnormality in at least one of three clinical tests, while only 10.7% of those eyes that appeared normal on the basis of these tests showed such progression. The difference was significant (p<0.04). These results suggest that the three clinical tests may be of value in detecting normal tension glaucoma eyes at risk for progression of visual field defects.

Effects of switching to SofZia-preserved travoprost in patients who presented with superficial punctate keratopathy while under treatment with latanoprost

PurposeTo investigate the effects of switching to SofZia-preserved travoprost (TRV) on superficial punctate keratopathy (SPK) observed in patients using benzalkonium chloride (BAC)-preserved latanoprost (LAT).MethodsPatients with either primary open-angle glaucoma or ocular hypertension treated with LAT for at least 1 month who presented with SPK participated in this prospective, multicenter, open-label uncontrolled study. After the switch from LAT to TRV, patients were monitored at 2 weeks and at 1, 2, and 3 months. The use of concomitantly employed ophthalmic solutions was continued during the observation period. The intensity of SPK in each of five areas defined on the cornea was scored on a standard scale. Repeated measurements were tested with a linear mixed model.ResultsOf the 48 patients enrolled, 45 patients completed the study. After the switch to TRV, the mean SPK score in the whole cornea decreased significantly at every observation point (P < 0.0001 at each point) while intraocular pressure did not change significantly. Throughout the observation period, the SPK score tended to be higher in patients using a larger number of concomitant medications that contained BAC.ConclusionSwitching to TRV improved SPK observed in a population using LAT, likely because of a decrease in exposure to BAC.

Influence of Myopic Disc Shape on the Diagnostic Precision of the Heidelberg Retina Tomograph

PURPOSE To investigate the diagnostic capability of a glaucoma diagnostic classification program for the Heidelberg Retina Tomograph (HRT) in eyes with myopic disc shapes. METHODS Sixty-six normal subjects (66 eyes) and 78 open-angle glaucoma patients (78 eyes) were enrolled. The eyes were divided into two groups; those eyes with myopic and those with nonmyopic disc shapes. The classification was based on clinical judgment made after the examination of stereophotographs of the discs without considering the refractive errors. The agreement between the classification program and the clinical diagnosis was evaluated for sensitivity, specificity, and diagnostic precision. The influence of the disc shape on the HRT topographic parameters was evaluated. RESULTS The sensitivity, specificity, and diagnostic precision of the HRT were 83%, 95%, and 89% in eyes with nonmyopic disc shapes, but 71%, 96%, and 83% in those with myopic disc shapes. Rim volume, height variation contour, mean retinal fiber nerve layer (RNFL) thickness, and RNFL cross-section area were significantly larger in eyes with myopic disc shapes than in eyes with nonmyopic discs, regardless of the clinical diagnosis. CONCLUSIONS The classification program should be modified to take into account the myopic disc shape in order to improve its capability to make more accurate diagnosis of glaucoma possible.

Topographic characteristics of the optic nerve head measured with scanning laser tomography in normal Japanese subjects

PurposeFew studies have been performed regarding the topographic information obtained with the Heidelberg retina tomograph (HRT) in normal Japanese. In this study, we examined the factors influencing optic disc parameters and hemisphere symmetry obtained with the HRT in normal Japanese subjects.MethodsMean values and the standard deviation range for the main HRT parameters were evaluated in 223 eyes of 223 normal Japanese subjects. The influence of age, sex, and disc size on HRT topographic data was analyzed. The superior and inferior hemisphere topographic parameters were compared.ResultsDisc area showed a significant difference by sex (P = 0.0493). Rim volume (r = −0.208, P = 0.019), height variation contour (r = −0.275, P = 0.001), and mean retinal nerve fiber layer (RNFL) thickness (r = −0.366, P = 0.001) declined with age. All parameters except height variation contour and mean RNFL thickness showed a clinically significant correlation with disc size (−0.159 < r < 0.719, P < 0.01). Cup parameters in the superior hemisphere were significantly greater than those in the inferior hemisphere. In contrast, rim parameters in the superior hemisphere were significantly smaller than those in the inferior hemisphere.ConclusionsSome factors, namely, sex, age, and disc size, affected the optic disc parameters in the HRT measurements. Possible parameter asymmetry between the two hemispheres should be considered in normal eyes. Jpn J Ophthalmol 2005;49:469–476

Changes in Optic Disc Parameters After Intraocular Pressure Reduction in Adult Glaucoma Patients

PURPOSE To quantitatively evaluate the change in the optic disc topographic parameters associated with reduction in the intraocular pressure (IOP) after trabeculectomy in adult patients with glaucoma. METHODS A series of 22 patients (mean age: 45.7+/-15.1 years) with several types of glaucoma were examined for various parameters of optic disc before and after trabeculectomy. Cup area, cup-to-disc area ratio, cup volume, rim volume, mean cup depth, and maximum cup depth were determined by means of laser scanning tomography (LST), and the parameters were correlated with the degree of postsurgical IOP decrease. RESULTS The IOP in adult glaucoma patients showed significant reductions after trabeculectomy. The values for all topographic parameters examined. except cup volume, showed statistically significant postsurgical changes as compared to the presurgical values. Of all postsurgical changes in parameters. the increase in the rim volume was the most noticeable; it was remarkably evident in those eyes with postsurgical IOP levels less than 15 mm Hg. It was also demonstrated that the anterior displacement of the glaucomatous cupping may occur after surgery. CONCLUSIONS It is obvious that optic disc parameters can change after IOP reduction after successful surgery in adult glaucoma patients as well as in infantile glaucoma patients. The site of changeable glaucomatous optic cupping is topographically variable among patients and it may be related to the presurgical shape of the optic cup.

Travoprost with sofZia ® preservative system lowered intraocular pressure of Japanese normal tension glaucoma with minimal side effects

Background This study aimed to evaluate the effect of travoprost with sofZia® preservative system for lowering the intraocular pressure (IOP) of Japanese normal tension glaucoma (NTG) patients. Methods In this prospective, multicenter, open-label study, Japanese NTG patients with baseline IOPs <20 mmHg were enrolled after three consecutive time measurements taken at screening and baseline visits. Travoprost with sofZia® was instilled once daily. Lowering effect on IOP, conjunctival hyperemia, superficial punctate keratopathy, and adverse events were examined at week 4, 8, and 12 after drug instillation. Results One-hundred and three of the 107 enrolled patients (baseline IOP =15.2±2.0 mmHg [mean ± standard deviation]) completed the study. The mean IOP value as well as percent reduction was significantly reduced at each visit after travoprost with sofZia® initiation (P<0.0001). The conjunctival hyperemia score was 1 or less throughout the study, though it increased significantly over time. No significant change was observed in superficial punctate keratopathy. The cumulative incidence of side effects such as eyelash changes, eyelid pigmentation, and deepening of the upper lid was 47.6%, 27.2%, and 16.5%, respectively. Conclusion Travoprost preserved with sofZia® effectively lowered the IOP of Japanese NTG patients. It was well tolerated with few discontinuations due to adverse events.

Frequency doubling technology and scanning laser tomography in eyes with generalized enlargement of optic disc cupping.

Purpose:To characterize functional and structural changes in eyes with generalized enlargement of optic disc cupping (vertical cup/disc ratio ≥0.8), normal intraocular pressure, normal standard achromatic automated perimetry (SAP) results, and no other ophthalmoscopic findings suggesting glaucoma (large C/D eyes) using frequency doubling technology (FDT) and the Heidelberg Retina Tomograph (HRT). Methods:This comparative observational case series included 30 large C/D eyes (30 subjects), 17 eyes (17 patients) with early-stage normal tension glaucoma with generalized enlargement of optic disc cupping (NTG eyes), and 25 eyes from 25 normal subjects (normal eyes). Results with Humphrey 30-2, FDT N-30 threshold programs, and HRT were compared among these groups. Large C/D eyes were subdivided into FDT-normal and -abnormal eyes according to the predetermined criteria and HRT parameters were compared among them. Results:No significant difference was seen in HRT parameters between the large C/D and NTG eyes. In the large C/D eyes, FDT mean deviation was lower than in the normal eyes and higher than in the NTG eyes, whereas FDT pattern standard deviation was smaller than in the NTG eyes (P = 0.02-0.03). Among HRT parameters, only cup shape measure (CSM) showed significant negative correlation with FDT mean deviation in the large C/D eyes. Between FDT-normal and -abnormal subgroups, only CSM showed significant difference (P < 0.01). Conclusion:Frequency doubling technology showed abnormalities in large C/D eyes. Only CSM showed significant correlation with FDT result and difference between those with normal and abnormal FDT results. In management of large C/D eyes, FDT and CSM will be useful to detect functional and structural change.

The efficacy and safety of add-on 0.1% brimonidine tartrate preserved with sodium chlorite in on-treatment Japanese normal-tension glaucoma patients

Background To evaluate the efficacy and safety of newly formulated brimonidine (0.1% brimonidine tartrate preserved with sodium chlorite: brimonidine) as add-on therapy in on-treatment Japanese normal-tension glaucoma (NTG) patients. Methods Brimonidine was added to on-treatment NTG patients with intraocular pressures (IOP) of between 13 mmHg and 16 mmHg after three consecutive IOP measurements. The time courses of IOP, conjunctival hyperemia, superficial punctate keratitis, and adverse events were examined at 4, 8, and 12 weeks after brimonidine instillation. Results Though 75 of 83 patients (31 males and 52 females; mean age: 63.4±11.6 years) completed the study, six patients discontinued because of side effects and two patients withdrew. The mean IOP after brimonidine addition at week 4 (12.6±1.8 mmHg, P<0.001), week 8 (12.4±1.7 mmHg, P<0.001), and week 12 (12.6±1.8 mmHg, P<0.001) was significantly decreased compared with that before the addition of brimonidine (13.9±1.2 mmHg). No significant changes in superficial punctate keratitis or conjunctival hyperemia scores were observed throughout the study. Dizziness, sleepiness, eye pain, and itching (mild to moderate) were noted in five, four, three, and three patients, respectively. Conclusions The addition of newly formulated brimonidine to on-treatment Japanese NTG patients with IOP of 13–16 mmHg further reduced the levels of IOP with minimal side effects and adverse events.

Assessment of retinal sensitivity using a time-saving strategy in normal individuals

Background The purpose of this study was to compare retinal sensitivities in normal individuals obtained using the Swedish Interactive Threshold Algorithm Standard (SITA-S) on the Humphrey field analyzer with those obtained using the Dynamic strategy on the Octopus. Methods Prior to visual field examinations, the background luminance, stimulus size, and exposure time with the Octopus 101 were conformed to the Humphrey field analyzer II settings. Volunteers over 20 years of age without apparent ophthalmic abnormalities were examined with the SITA-S central 30-2 program followed by the Dynamic 32 program. Eye with corrected visual acuity ≥ 0.8, refraction ≥ −6.0 diopters, and fields with satisfactory levels of reliability in SITA-S and Dynamic were selected. Results Sixty-seven eyes from 67 normal individuals of mean age 51.3 ± 16.3 (range 22–76) years satisfied the selection criteria and were analyzed. Mean retinal sensitivity was significantly (P < 0.0001) higher with SITA-S (29.0 ± 2.4 dB) than with Dynamic (26.8 ± 2.1 dB). Changes in retinal sensitivity with increasing age were significantly (P = 0.0003) greater with Dynamic (−0.09 ± 0.04 dB/year; 95% confidence interval [CI] −0.10 to −0.08 dB/year) than with SITA-S (−0.07 ± 0.04 dB/year, 95% CI −0.08 to −0.06 dB/year). When classifying the visual field into three areas (central, mid-peripheral, and peripheral), retinal sensitivities with SITA-S were significantly higher in all areas than with Dynamic (P < 0.0001 for all three areas). Conclusion Differences in Dynamic and SITA-S strategies may contribute to the differences in retinal sensitivities observed in normal individuals.

Addition of or Switch to Topical Bunazosin Hydrochloride in Elderly Patients with Normal-Tension Glaucoma : A One-Year Follow-up Study

PurposeTo evaluate the efficacy and safety of 0.01% bunazosin hydrochloride ophthalmic solution (bunazosin) for elderly patients with normal-tension glaucoma (NTG) as an addition to or instead of their previous therapy.MethodsBunazosin was administered to NTG patients aged 65 years or over who had been undergoing topical glaucoma therapy. In accordance with the study protocol, intraocular pressure (IOP) and visual field measurement were performed and the safety of the treatment was evaluated periodically between week 0 and week 52 at the five facilities where the study was carried out.ResultsOf the 98 enrolled patients, 84 (85.7%) were followed up for 52 weeks. During the follow-up period, IOP significantly and persistently decreased (week 0, 15.0 ± 2.5 mmHg; week 52, 13.4 ± 2.4 mmHg, P < 0.0001), but the decrease in mean deviation (MD) was not significant. Although no systemic adverse reactions were observed, local adverse events were noted in 7 of the 98 patients.ConclusionsThe addition of or the switch to bunazosin in elderly NTG patients resulted in a significant reduction of IOP without apparent exacerbation of visual field defects or systemic or local adverse reactions other than conjunctival hyperemia. Jpn J Ophthalmol 2006;50:443–448