Toyoaki Tsumura

Association between Nocturnal Blood Pressure Reduction and Progression of Visual Field Defect in Patients with Primary Open-Angle Glaucoma or Normal-Tension Glaucoma

PurposeTo assess prospectively the relationship between nocturnal blood pressure reduction (dip) and progression of the visual field defect in patients with normal-tension glaucoma (NTG) or primary open-angle glaucoma (POAG).Patients and MethodsThe subjects studied were 38 patients with glaucoma (23 patients with NTG, 15 patients with POAG), in whom 48-h ambulatory blood pressure monitoring was conducted, who were followed for at least 4 years, and in whom reliable visual field tests were performed at least 5 times. The progression was determined by the mean deviation (MD) slope analysis system installed in the Humphrey field analyzer Statpac program. Glaucoma patients with a dip of <10% were assigned to the nondipper group, those with a dip of 10%–20% to the tipper group, and those with a dip of >20% to the extreme dipper group. The dipper group was defined as physiologic dippers, while the nondipper and the extreme dipper groups were defined as nonphysiologic dippers, to study the relationship between the disturbance of the dip and progression of the visual field defect.ResultsThirteen patients showed significant progression, while 25 patients did not. There were no significant differences in the mean intraocular pressure and follow-up period between the patients with progression and those without progression. Half (7/14) of the nondippers, 20% (4/20) of the dippers, and 50% (2/4) of the extreme dippers showed progression, indicating a tendency of progression in the nondipper and the extreme dipper groups. The nonphysiologic dippers had a higher incidence of progression compared with the physiologic dippers (P = 0.05). Among the glaucoma patients in the nondipper and dipper categories only, those with progression had significantly smaller dips (P = 0.02).ConclusionThese results suggest that disturbance in the physiologic dip may be involved in the progression of glaucoma.

Circadian rhythm of autonomic nervous function in patients with normal-tension glaucoma compared with normal subjects using ambulatory electrocardiography

Purpose: To compare circadian rhythm of autonomic nervous function in patients with normal‐tension glaucoma with subjects with normal eyes. Methods: Thirty‐two patients with normal‐tension glaucoma and 32 age‐matched normal subjects who had no history of systemic disorders and no currently treated systemic disorders, especially diseases of the autonomic nervous system, were studied. An ambulatory electrocardiogram was installed that recorded heartbeats for 48 hours. Low‐frequency and high‐frequency values were calculated as markers of the autonomic nervous system status based on heart‐rate variability using a power‐spectrum analysis. Results: The low‐frequency values of patients with normal‐tension glaucoma during the spans of an active day and a resting night were significantly greater than those of normal subjects, and this difference was emphasized during the night resting span. However, the high‐frequency values of patients with normal‐tension glaucoma were similar to those of normal subjects. The normal subjects showed a significant agerelated decrease in all investigated parameters except the low‐frequency values during the resting span. However, the patients with normal‐tension glaucoma showed a significant age‐related decrease only in low‐frequency values during the active day. Patients with normal‐tension glaucoma with progressive visual field defects showed much greater values than other cases, although the values were not significantly different. Conclusion: These results indicate that a disturbance of the circadian rhythm of the autonomic nervous system may exist in patients with normal‐tension glaucoma.

Angiographic lesion size associated with LOC387715 A69S genotype in subfoveal polypoidal choroidal vasculopathy.

Purpose: To investigate whether the LOC387715/ARMS2 variants are associated with an angiographic phenotype, including lesion size and composition, in subfoveal polypoidal choroidal vasculopathy. Methods: Ninety-two subjects with symptomatic subfoveal polypoidal choroidal vasculopathy, whose visual acuity was from 0.1 to 0.5 on the Landolt chart, were genotyped for the LOC387715 polymorphism (rs10490924) using denaturing high-performance chromatography. The angiographic phenotype, including lesion composition and size, was evaluated by evaluators who were masked for the genotype. Lesion size was assessed by the greatest linear dimension based on fluorescein or indocyanine green angiography. Results: Although there was no statistically significant difference in lesion size on indocyanine green angiography (P = 0.36, Kruskal-Wallis test) and in lesion composition (P = 0.59, chi-square test) among the 3 genotypes, there was a statistically significant difference in lesion size on fluorescein angiography (P = 0.0022, Kruskal-Wallis test). Conclusion: The LOC387715 A69S genotype is not associated with lesion composition or size on indocyanine green angiography but with lesion size on fluorescein angiography in patients with subfoveal polypoidal choroidal vasculopathy. Because fluorescein angiography findings represent secondary exudative changes, including subretinal hemorrhages and retinal pigment epithelial detachment, the results in the present study likely indicate that the T allele at the LOC387715 gene is associated with the exudative activity of polypoidal lesions.

Ultrasound biomicroscopic study of ciliary body thickness in eyes with narrow angles

PURPOSE To determine the ciliary body thickness and other biometric findings in eyes with narrow angles. METHODS Eighteen otherwise normal eyes with narrow angles in 18 Japanese patients and 18 normal control eyes with open angles in 18 age-matched and sex-matched Japanese patients were studied. A-scan ultrasonography was performed to measure anterior chamber depth, lens thickness, axial length, and relative lens position. Ultrasound biomicroscopy was also performed to obtain measurements of the anterior ocular structures, including anterior chamber depth and ciliary body thickness at sites 1 mm and 2 mm posterior to the scleral spur (positions 1 and 2, respectively). RESULTS Compared with normal control eyes, the narrow-angle eyes showed a shallower anterior chamber (narrow angle, 1.87 +/- 0.27 mm; control, 2.69 +/- 0.26 mm; P <.0001), a thicker lens (4.97 +/- 0.49 mm, 4.26 +/- 0.53 mm; P <.0001), a more anteriorly located lens (2. 21 +/- 0.13, 2.35 +/- 0.14; P <.0001), a shorter axial length (22.70 +/- 0.97 mm, 23.41 +/- 0.86 mm; P =.012), and a thinner ciliary body (position 1: 454 +/- 107 microm, 602 +/- 86 microm; P <.0001; position 2: 203 +/- 50 microm, 321 +/- 68 microm; P <.0001). Lens thickness was significantly correlated with ciliary body thickness at positions 1 (R(2) = 0.34; P =.0001) and 2 (R(2) = 0.43; P <.0001). Anterior chamber depth was significantly correlated with ciliary body thickness at positions 1 (R(2) = 0.48; P <.0001) and 2 (R(2) = 0.56; P <.0001). CONCLUSION Thinning of the ciliary body may be one of the important factors associated with the anterior location of the lens, the increased lens thickness, and the decreased anterior chamber depth in eyes with a narrow angle.

Comparison between newly developed scanning peripheral anterior chamber depth analyzer and conventional methods of evaluating anterior chamber configuration.

PurposeTo compare the newly developed scanning peripheral anterior chamber depth analyzer (SPAC) with the Van Herick technique, the Shaffer grading system, and ultrasound biomicroscopy (UBM), in terms of accuracy of measurement of peripheral anterior chamber depth (ACD). MethodsThe subjects were well-controlled glaucoma patients who were being treated at the University of Yamanashi Hospital. Ten eyes from each of the 4 groups classified as Shaffer grades 1 to 4 were evaluated by SPAC, the Van Herick technique, and UBM. All measurements were performed independently on the temporal side in a masked fashion. SPAC evaluated ACD consecutively from the pupil center to the limbus at 0.4 mm intervals. UBM measurements were carried out at a depth of 500 μm (angle-opening distance 500) from the scleral spur. A dummy eye was used for evaluating SPAC measurement accuracy. ResultsThe results of SPAC measurement were well correlated with those of the Van Herick technique and the Shaffer grading system. The SPAC measurement results were also significantly correlated with angle-opening distance 500. The correlation coefficients at distances of 2, 4, 4.8, and 5.6 mm from the pupil center were r=0.68, 0.69, 0.69, and 0.61, respectively, and the P values of all the correlations were less than 0.0001. Study of the dummy eye revealed that SPAC has high accuracy for measuring ACD and that the coefficient variances were less than 1.0% at all measured points. ConclusionsThe results of SPAC measurement correlate well with those of the conventional methods.

Bimatoprost ophthalmic solution 0.03% lowered intraocular pressure of normal-tension glaucoma with minimal adverse events.

Purpose The aim of this study was to evaluate the efficacy and safety of bimatoprost ophthalmic solution 0.03% (bimatoprost) in Japanese normal-tension glaucoma (NTG) patients with an intraocular pressure (IOP) of 18 mmHg or less. Methods Bimatoprost was instilled into the unilateral conjunctival sac of Japanese NTG patients with a baseline IOP of 18 mmHg or less. The time courses of IOP, conjunctival hyperemia, superficial punctate keratitis, and adverse events were examined at 2, 4, 8, and 12 weeks post bimatoprost instillation. Results Thirty-two of the 38 enrolled NTG patients (mean age, 64.1 ± 12.6 years; 19 males and 19 females) completed the study, with six patients unable to complete the study (two patients discontinued because of side effects and four patients withdrew). The levels of IOP in the treated eyes were significantly reduced (P < 0.0001) from the baseline IOP levels. No significant change in IOP was observed in the fellow eyes. There were significant increases in conjunctival hyperemia. No significant superficial punctate keratitis scores were noted between the baseline and each point examined. Eyelash disorder, eyelid pigmentation, and deepening of the upper eyelid sulcus were observed in 28, six, and three eyes, respectively. Conclusion Bimatoprost effectively lowered the IOP. It was well tolerated in Japanese NTG patients, with few patients having to discontinue because of adverse events.

Long-term Effects of Latanoprost Monotherapy on Intraocular Pressure in Japanese Glaucoma Patients

PurposeTo assess the long-term effects of latanoprost monotherapy on intraocular pressure (IOP) reduction in Japanese patients with glaucoma. MethodsThose enrolled were patients with glaucoma who had been treated on an outpatient basis for more than 5 years at the Glaucoma Outpatient Clinic of the University of Yamanashi Hospital, with only latanoprost ophthalmic solution as the first drug of choice. Subjects who underwent treatment with a drug other than latanoprost, laser therapy, or surgery were eliminated from the study, and IOP reduction by latanoprost, the dropout rate and causative reasons, and the types of additional therapy were assessed in a retrospective manner. ResultsSeventy-two patients (age: 68.3±13.0 y) were enrolled, including 40 men and 32 women for the checking of 72 eyes. There were 47 eyes with normal tension glaucoma (NTG) and 25 with primary open angle glaucoma (POAG). The mean duration of latanoprost monotherapy was 4.1±2.0 years (range: 5 mo to 7 y, median: 4.0 y). IOP reduction rates (cumulative dropout rates) relative to the mean IOP before the start of latanoprost monotherapy (17.8±3.4 mm Hg) were 11.5% (8.3%), 15.5% (8.3%), 13.0% (9.7%), 13.4% (13.9%), 13.5% (19.4%), and 10.6% (30.6%) at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years after the start of monotherapy, respectively. Although latanoprost demonstrated significant IOP reduction in POAG and NTG, eyes with POAG showed significant IOP reduction than those with NTG. Two eyes presented with local adverse events resulting from the discontinuation of use of latanoprost, and 4 eyes required filtering surgery. ConclusionsLatanoprost stably reduced IOP over a long term and maintained visual field in approximately 70% of eyes with glaucoma after treatment for 5 years.

Photodynamic therapy for polypoidal choroidal vasculopathy: baseline perimetric results and visual outcomes.

PurposeTo investigate whether the baseline mean deviation (MD) of Humphrey perimetry has a predictive value for visual improvement after photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV).MethodsWe retrospectively reviewed the records of 40 eyes of 39 PCV patients (28 men, 11 women) who underwent PDT. The follow-up period ranged from 12 to 42 months. Best-corrected visual acuity (BCVA) improved more than 0.2 logarithm of the minimum angle of resolution (logMAR) units at the final examination in 22 (55%) of the 40 eyes, which were classified into the “Improved group.” The other 18 eyes with improvement of ≤0.2 logMAR units were classified into the “Not Improved group.”ResultsThe baseline MD in the Improved group was significantly better than that in the Not Improved group (P = 0.0144). Multivariate analysis confirmed that only the baseline MD was associated with improvement of the final BCVA, showing that eyes with better baseline MD tended to exhibit improvement of the final BCVA after PDT for PCV (odds ratio = 1.303; 95% confidence interval, 1.069–1.588).ConclusionsThe baseline MD in Humphrey perimetry can be useful for predicting visual improvement after PDT for PCV.

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.

Humphrey Perimetry as a Predictor of Visual Improvement After Photodynamic Therapy

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