Effects of brinzolamide vs timolol as an adjunctive medication to latanoprost on circadian intraocular pressure control in primary open-angle glaucoma Japanese patients

Makoto Ishikawa1,2, Takeshi Yoshitomi11Department of Ophthalmology, Akita University Faculty of Medicine, Akita, Japan; 2Department of Ophthalmology, Ogachi Central Hospital, Akita, JapanPurpose: To study the effect of the concomitant use of brinzolamide and latanoprost on the 24-hour variation in intraocular pressure (IOP) in primary open-angle glaucoma (POAG) patients first treated with timolol and latanoprost.Methods: We studied 30 eyes from 30 POAG patients previously treated with latanoprost monotherapy. After a washout of four weeks in both eyes, all patients were treated with 0.5% timolol and latanoprost. Three months after the initiation of treatment with timolol and latanoprost, the 24-hour IOP variation was measured. Thereafter, all patients were treated with concomitant 1% brinzolamide and latanoprost. Three months after changing the therapeutic regimen, the 24-hour IOP variation was measured a second time. Latanoprost was administered once a day, and timolol and brinzolamide were twice a day. IOP was measured with a noncontact tomometer.Results: On treatment with brinzolamide and latanoprost, a significant decrease in IOP compared to timolol and latanoprost was observed at all time points except at 3 PM and 6 PM. As a group, the patients had a significantly lower diurnal mean IOP and nocturnal mean IOP during treatment with brinzolamide and latanoprost than with timolol and latanoprost.Conclusions: Treatment of POAG with a combination of brinzolamide and latanoprost demonstrated improved hypotensive effects compared with timolol and latanoprost during a 24-hour period.Keywords: circadian intraocular pressure, adverse effects, timolol, brinzolamid

Risk factors for primary open-angle glaucoma in Japanese subjects attending community health screenings

Makoto Ishikawa, Yu Sawada, Noriko Sato, Takeshi YoshitomiDepartment of Ophthalmology, Akita Graduate University School of Medicine, Akita, JapanBackground/aims: To describe risk factors associated with primary open-angle glaucoma (POAG) in Japanese subjects who participated in community health screenings.Methods: Residents of Akita, Japan, participating in a community health checkup were selected to undergo a comprehensive ophthalmic examination. Glaucoma was diagnosed based on optic disk appearance, perimetric results, and other ocular findings. Systemic blood pressure and intraocular pressure were measured and ocular perfusion pressure was calculated. Logistic regression analysis was performed to determine risk factors for POAG patients.Results and conclusion: Of the 710 subjects examined, 26 had POAG. The estimated prevalence of POAG was 3.7%. After adjusting for age, the prevalence of POAG was similar to that found in the Tajimi Study of Japanese subjects. Multivariate logistic regression analysis demonstrated that older age (≥60 years, odds ratio [OR]: 3.49), lower diastolic blood pressure (≤58 mmHg, OR: 2.11), higher intraocular pressure (≥19 mmHg, OR: 4.12), and lower ocular perfusion pressure (≤34 mmHg, OR: 5.78) were associated with increased risk of having POAG. These findings may be relevant for identifying high risk groups.Keywords: glaucoma, community health screening, risk factor

Peripheral T-cell lymphoma of the eyelid

Makoto Ishikawa, Hiroshi Watabe, Masahiro Hayakawa, Takeshi YoshitomiDepartment of Ophthalmology, Akita University Faculty of Medicine, Akita, JapanPurpose: To report a case of a 25-year-old woman with previously treated peripheral T-cell lymphoma (PTCL) presenting with a recurrent lower eyelid lesion.Patients and method: Case report.Results: A 25-year-old young woman with previously treated PTCL noted an induration in the skin of her left lower eyelid. Upon diagnosis of a chalazion, antibiotic eye drops and ointments as well as steroid eye drops were administered. However, the condition worsened rapidly and swelling of the lower eyelid became remarkable. An excisional biopsy revealed that the palpebral lesion was diagnosed as recurrence of PTCL. Electron irradiation was applied as a radical treatment, and the prognosis was satisfactory without recurrence at 10 months after the last irradiation.Conclusions: Although lymphoma isolated to the ocular adnexa is rare, it should always be included in the differential diagnosis of any patient presenting with progressive swelling of the eyelid or ocular region.Keywords: peripheral T-cell lymphoma, chalazion, eyeli

24(S)-Hydroxycholesterol protects the ex vivo rat retina from injury by elevated hydrostatic pressure

In the central nervous system, 24(S)-hydroxycholesterol (24(S)-HC) is an oxysterol synthesized from cholesterol by cholesterol 24-hydroxylase (CYP46A1) encoded by the cyp46a1 gene. In the present study using a rat ex vivo glaucoma model, we found that retinal 24(S)-HC synthesis is facilitated by pressure elevation. Moreover, we found that 24(S)-HC is neuroprotective against pressure mediated retinal degeneration. Quantitative real-time RT-PCR, ELISA, and immunohistochemistry revealed that elevated pressure facilitated the expression of cyp46a1 and CYP46A1. Immunohistochemically, the enhanced expression of CYP46A1 was mainly observed in retinal ganglion cells (RGC). LC-MS/MS revealed that 24(S)-HC levels increased in a pressure-dependent manner. Axonal injury and apoptotic RGC death induced by 75 mmHg high pressure was ameliorated by exogenously administered 1 μM 24(S)-HC. In contrast, voriconazole, a CYP46A1 inhibitor, was severely toxic even at normobaric pressure. Under normobaric conditions, 30 μM 24(S)-HC was required to prevent the voriconazole-mediated retinal damage. Taken together, our findings indicate that 24(S)-HC is facilitated by elevated pressure and plays a neuroprotective role under glaucomatous conditions, while voriconazole, an antifungal drug, is retinotoxic. 24(S)-HC and related compounds may serve as potential therapeutic targets for protecting glaucomatous eyes from pressure-induced injuries

Association of Myopic Deformation of Optic Disc with Visual Field Progression in Paired Eyes with Open-Angle Glaucoma

Purpose The influence of myopia on glaucoma progression remains unknown, possibly because of the multifactorial nature of glaucoma and difficulty in assessing a solo contribution of myopia. The purpose of this study is to investigate the association of myopia with visual field (VF) progression in glaucoma using a paired-eye design to minimize the influence of confounding systemic factors that are diverse among individuals. Methods This retrospective study evaluated 144 eyes of 72 subjects with open-angle glaucoma, with similar intra-ocular pressure between paired eyes, spherical equivalent (SE) = 24 mm. Paired eyes with faster and slower VF progression were grouped separately, according to the global VF progression rate assessed by automated pointwise linear regression analysis. The SE, axial length, tilt ratio and torsion angle of optic discs, Bruch\u27s membrane (BM) opening area, and gamma zone parapapillary atrophy (PPA) width were compared between the two groups. Factors associated with faster VF progression were determined by logistic regression analysis. Results The mean follow-up duration was 8.9 +/- 4.4 years. The mean value of SE and axial length were -6.31 +/- 1.88 D and 26.05 +/- 1.12 mm, respectively. The mean global visual field progression rate was -0.32 +/- 0.38 dB/y. Tilt ratio, BM opening area, and gamma zone PPA width were significantly greater in the eyes with faster VF progression than those with slower progression. In multivariate analysis, these factors were significantly associated with faster VF progression (all P < 0.05), while SE and axial length were not associated with it. Conclusion In myopic glaucoma subjects, tilt of the optic disc and temporal shifting and enlargement of the BM opening were associated with faster rate of VF progression between paired eyes. This suggests that myopia influences VF progression in glaucomatous eyes via optic disc deformations rather than via refractive error itself

24(S)-Hydroxycholesterol protects the ex vivo rat retina from injury by elevated hydrostatic pressure

In the central nervous system, 24(S)-hydroxycholesterol (24(S)-HC) is an oxysterol synthesized from cholesterol by cholesterol 24-hydroxylase (CYP46A1) encoded by the cyp46a1 gene. In the present study using a rat ex vivo glaucoma model, we found that retinal 24(S)-HC synthesis is facilitated by pressure elevation. Moreover, we found that 24(S)-HC is neuroprotective against pressure mediated retinal degeneration. Quantitative real-time RT-PCR, ELISA, and immunohistochemistry revealed that elevated pressure facilitated the expression of cyp46a1 and CYP46A1. Immunohistochemically, the enhanced expression of CYP46A1 was mainly observed in retinal ganglion cells (RGC). LC-MS/MS revealed that 24(S)-HC levels increased in a pressure-dependent manner. Axonal injury and apoptotic RGC death induced by 75 mmHg high pressure was ameliorated by exogenously administered 1 mu M 24(S)-HC. In contrast, voriconazole, a CYP46A1 inhibitor, was severely toxic even at normobaric pressure. Under normobaric conditions, 30 mu M 24(S)-HC was required to prevent the voriconazole-mediated retinal damage. Taken together, our findings indicate that 24(S)-HC is facilitated by elevated pressure and plays a neuroprotective role under glaucomatous conditions, while voriconazole, an antifungal drug, is retinotoxic. 24(S)-HC and related compounds may serve as potential therapeutic targets for protecting glaucomatous eyes from pressure-induced injuries

Association of Myopic Optic Disc Deformation with Visual Field Defects in Paired Eyes with Open-Angle Glaucoma: A Cross-Sectional Study

Purpose To examine the association of myopia with the visual field (VF) defects in open-angle glaucoma (OAG) using paired eyes to eliminate the effect of unknown confounding factors that are diverse among individuals. Methods One hundred eighteen eyes of 59 subjects with myopia (spherical equivalent [SE] >= -2 diopter [D] and axial length >= 24.0 mm) whose intra-ocular pressure between paired eyes was similar and the mean deviation (MD) of the Humphrey VF test differed by more than 6 dB were included. Refractive errors (SE, axial length) and parameters associated with the papillary and parapapillary myopic deformation (tilt ratio, torsion angle, and beta-zone parapapillary atrophy [PPA] area without Bruch\u27s membrane) were measured in each eye. The paired eyes were divided into worse and better eyes according to the MD of the VF, and parameters were compared between them. Further, multiple linear regression analysis was performed to examine the correlation of the difference in various parameters with the MD difference between paired eyes. Results The SE of all eyes was -6.39 +/- 2.15 D (mean +/- standard deviation) and axial length was 26.42 +/- 1.07 mm. MD of the worse and better VF eyes were -13.56 +/- 6.65 dB and -4.87 +/- 5.32 dB, respectively. Eyes with worse VFs had significantly greater SE, axial length, tilt ratio, and PPA area without Bruch\u27s membrane than those with better VFs (all P < 0.05). In multiple linear regression analysis, the difference of the MD between paired eyes was significantly correlated with the difference in the tilt ratio and PPA area without Bruch\u27s membrane. Conclusion The myopic papillary and parapapillary deformations, but not refractive error itself, were related to the worse VF in paired eyes with OAG. This suggests that myopia influences the severity of the glaucomatous VF defects via structural deformation