Long-term Side Effects Including Blepharitis Leading to Discontinuation of Ripasudil.

PRECIS: Blepharitis was the most common side effect leading to discontinuation of ripasudil therapy. Prior allergic reactions to other topical glaucoma were found to be a risk factor for ripasudil-induced blepharitis. PURPOSE: To report the incidence proportion of blepharitis and its relating factors due to long-term use of 0.4% riapasudil, a Rho-kinase inhibitor, in glaucoma patients of a clinical setting. PATIENTS AND METHODS: One hundred three eyes of 103 consecutive glaucoma patients who started ripasudil treatment between December 2014 and February 2017 at our institute, and who had a follow-up period of over 6 months were enrolled in this study. Incidence proportion, time required for recovery and risk factors associated with blepharitis and other side effects that led to discontinuation of ripasudil treatment were considered. RESULTS: The most frequently observed side effect was blepharitis (25.2%). The 12- and 24-month discontinuation rate due to blepharitis was 21.1%±8.2% and 34.6%±11.8% (average±SE), respectively (Kaplan-Meier analysis). Most patients recovered from blepharitis symptoms within 4 weeks, but 5 patients required over 8 weeks for recovery. Past history of allergic reactions to other topical glaucoma medication was significantly correlated with the manifestation of blepharitis (Cox proportional hazard model, P<0.007) while age, sex, intraocular pressure reduction rate, number of administered eye drops, history of systemic allergic diseases were not. CONCLUSIONS: Blepharitis was the most common reason for discontinuation of ripasudil treatment. Although most cases were resolved spontaneously, prolonged blepharitis was observed in a few patients. A past history of allergic reaction to other glaucoma medication indicates a higher possibility of blepharitis with ripasudil use and warrants careful administration.

Beta-peripapillary atrophy of the optic disc and its determinants in Japanese eyes: a population-based study.

PURPOSES: To assess ß-zone of peripapillary atrophy (ß-PPA) and its relationship between systemic and ocular factors, especially glaucoma, in a Japanese population. METHODS: Fundus photographs obtained from 2129 normal, 84 primary open-angle glaucoma (POAG) and 10 primary angle closure glaucoma subjects from 3021 participants aged 40 years or older in the Tajimi Study were analysed planimetrically. If both eyes of a subject met inclusion criteria, one eye was randomly chosen. RESULTS: The presence rates of ß-PPA were 54.7 and 77.4% (p < 0.001) and ß-PPA area averaged 0.67 and 1.06 mm2 (p < 0.001), in normal and POAG eyes, respectively. Myopia was closely related to disc ovality and ß-PPA. In normal eyes, logistic analysis showed that the presence of ß-PPA was correlated with older age, female gender, myopic refraction, thicker central corneal thickness (CCT), greater disc ovality and disc centre to fovea (disc-fovea) distance and lower intraocular pressure (IOP) (p = 0.039 ~ <0.001); and multiple regression analysis showed that ß-PPA area was correlated with older age, myopic refraction, greater disc area and ovality, disc-fovea distance and lower IOP (p = 0.004 ~ <0.001) after adjusting other factors. CONCLUSIONS: The presence and size of ß-PPA in normal eyes were correlated with older age, greater disc ovality and disc-fovea distance and lower IOP. Further, its presence was associated with female gender, thicker CCT and its size with greater disc area. ß-zone of peripapillary atrophy (ß-PPA) was also associated with POAG. These results provide reference data of the ß-PPA in a Japanese population and possibly indicate clinical importance of ß-PPA in glaucoma clinic.

Morphology of the optic disc in the Tajimi Study population.

PURPOSE: To assess optic disc morphology and disc-fovea distance (DF)/mean disc diameter (DD) ratio and related factors in Japanese subjects in a population-based setting. METHODS: Digital fundus photographs obtained from 2634 subjects, comprising 87% of 3021 participants aged 40 years or older in the Tajimi Study, a population-based glaucoma survey, were analyzed planimetrically. RESULTS: The disc size averaged 2.28 mm2, the ovality (maximal/minimal disc diameter ratio) 1.12 and the DF/DD ratio 2.94. After adjusting for other systemic and ocular factors, the disc size was correlated with the spherical equivalent refraction (SE), the ovality and DF/DD ratio correlated negatively with the SE and disc size (P < 0.0001). These parameters did not differ significantly between 2095 ophthalmologically normal eyes and 58 eyes with open angle glaucoma (OAG). The angle of the long axis of the discs with ovality of >1.10 was between 91° and 120° in 53% of the subject eyes. CONCLUSIONS: The reference data of disc morphology and DF/DD ratio in a Japanese population were obtained. SE showed significantly negative correlation with disc size, and disc size and SE showed significant negative correlation with ovality and DF/DD ratio. There was no significant difference between normal and OAG eyes evaluated by disc morphology and DF/DD ratio.

Visual Field Progressive Rate in Normal Tension Glaucoma Before and After Trabeculectomy: A Subfield-Based Analysis.

PURPOSE: To compare pretrabeculectomy and posttrabeculectomy progression rates in normal-tension glaucoma in 6 subfields of the central 30 visual field. DESIGN: A retrospective study. METHODS: Clinical records of 34 patients with normal-tension glaucoma (12 males and 22 females) with progressive visual field loss undergoing successful trabeculectomy were studied. The time course of the mean deviation (MD) and mean of total deviation in the superior/inferior arcuate, paracentral, and cecocentral subfields were analyzed using a linear mixed-effects model. RESULTS: Patients' age, intraocular pressure (IOP), MD, and pretrabeculectomy and posttrabeculectomy follow-up averaged 57.7 ± 9.6 years, 15.7 ± 1.7 mm Hg, -12.7 ± 5.5 dB, and 4.6 ± 1.5 and 5.7 ± 1.2 years, respectively. Average IOP was lowered by 6.1 ± 3.3 to 10.3 ± 2.7 mm Hg (5-14 mm Hg) over the postoprerative period with MD change rate of -0.25 dB/y (P < 0.003), which was slower (P < 0.001) than the preoperative one (-0.70 dB/y). The preoperative mean of total deviation change rate (-0.31 to -1.35 dB/y) improved postoperatively in the superior and inferior paracentral subfields (P < 0.001), whereas it remained unchanged in the inferior cecocentral/arcuate subfields (P > 0.10). The postoperative rate of progression showed no significant variation in these subfields. CONCLUSIONS: The rate of progression significantly varied among the 6 subfields preoperatively. It was significantly slowed down in the superior subfields by surgical IOP reduction, but not in the inferior cecocentral/arcuate subfields.

Iridotrabecular contact observed using anterior segment three-dimensional OCT in eyes with a shallow peripheral anterior chamber.

PURPOSE: To evaluate the prevalence and range of iridotrabecular contact (ITC) in eyes with a shallow peripheral anterior chamber (AC) by using anterior segment swept-source optical coherence tomography (AS-SS-OCT) and to compare the results with those obtained with ultrasound biomicroscopy (UBM) and gonioscopy. METHODS: Forty-three shallow peripheral AC eyes in 43 consecutive patients underwent gonioscopy. Cross-sectional images throughout the angle circumference (i.e., 360°) were obtained with AS-SS-OCT (SS-1000 noncontact, noninvasive three-dimensional imaging system) and those of the peripheral AC at the 3, 6, 9, and 12 o'clock positions were obtained with UBM (UD-1000). RESULTS: ITC evaluated with AS-SS-OCT included all gonioscopically identified peripheral anterior synechia (PAS) in the area. With AS-SS-OCT, at least one ITC was found in 40 (93.0%) and 42 (97.7%) of the 43 eyes under light and dark conditions, respectively, whereas with UBM, at least one ITC was found in 22 (51.1%) and 36 (83.7%) of the 43 eyes under light and dark conditions. The prevalence of ITC in eyes with AS-SS-OCT was significantly higher than that with UBM under light conditions, but not under dark conditions (P = 0.0001, 0.07, respectively, sign test). The PAS-positive eyes had a significantly greater ITC range than the PAS-negative eyes under light conditions (P = 0.006), but not under dark conditions (P = 0.08). CONCLUSIONS: AS-SS-OCT detected all PAS and the prevalence of ITC detected by AS-SS-OCT in narrow angle eyes was markedly higher than previously thought. A relationship between the ITC range under light conditions and future PAS formation was suggested.

Frequency doubling technology for earlier detection of functional damage in standard automated perimetry-normal hemifield in glaucoma with low-to-normal pressure.

PURPOSE: To compare the longitudinal change of frequency doubling technology (FDT) perimetry and standard automated perimetry (SAP) results in SAP-normal hemifield in open-angle glaucoma (OAG) eyes with low-to-normal intraocular pressure (IOP). MATERIALS AND METHODS: FDT perimetry with the N-30 full threshold protocol and SAP using the Humphrey Field Analyzer with the 30-2 Swedish Interactive Threshold Algorithm-standard protocol were periodically performed for at least 3 years in 39 eyes of 39 OAG patients with low-to-normal IOP and visual field damage confined to only one hemifield. The time courses of the mean of the threshold values of FDT and the mean of total deviations (TDs) in SAP-normal and SAP-abnormal fields were analyzed using a linear mixed model. RESULTS: The average follow-up was 4.9 years and the average IOP during follow-up was 12.6 mm Hg with or without medication. The aging effect-corrected rate of change in the mean FDT threshold values was significantly negative (P=0.004) in the SAP-normal hemifield, whereas that of mean of TD values by SAP did not significantly differ. In the SAP-abnormal hemifield, the rate of change was significantly negative for both tests (P<0.001). The mean of the slope of the mean TD values in the SAP-abnormal hemifield was significantly more negative than that in the SAP-normal hemifield (P=0.011), whereas that of the mean FDT threshold values showed no significant difference between the 2 hemifields. CONCLUSIONS: FDT is useful for monitoring functional damage in the SAP-normal hemifield in OAG eyes with low-to-normal IOP.

Identification of Schlemm's canal and its surrounding tissues by anterior segment fourier domain optical coherence tomography.

PURPOSE: To identify Schlemm's canal (SC) and trabecular meshwork (TM) by anterior segment Fourier-domain optical coherence tomography (AS-FD-OCT) with histologic confirmation in enucleated human eyes and to quantitatively evaluate SC and TM in living human eyes. METHODS: In enucleated human eyes, the imaging of the anterior chamber angle by AS-FD-OCT was performed before and after surgical expansion of SC with an injection of a viscoelastic material, followed by histologic examination. In 60 living human eyes, the agreement of identification of SC between examiners was evaluated with the Cohen's κ values, and the lengths of SC and TM and the area of TM were measured on temporal and nasal sections of the AS-FD-OCT images. RESULTS: In enucleated human eyes, SC was observed to be a thin, linear, lucent space in the AS-FD-OCT image obtained with the high-definition raster scan protocol, but not in those obtained with the bi-angle radial scan protocol. This space was enlarged after the SC expansion. In the histologic study, the SC was confirmed to be in the same position as in the AS-FD-OCT images. The κ values of observable SC in living human subjects were 0.92 or higher. The axial length of the SC averaged 347.2 ± 42.3 µm, TM length 466.9 ± 60.7 µm, and TM area 0.0671 ± 0.0058 mm². These measurements showed sufficient repeatability and reproducibility. CONCLUSIONS: Using the high-definition images of the AS-FD-OCT, SC and its surrounding tissues were successfully observed in most of the living eyes and were quantitatively evaluated in a noninvasive manner.