Prostaglandin-Associated Periorbitopathy Symptom Alleviation After Switching Prostaglandin F Receptor Agonist to EP2 Receptor Agonist in Patients with Glaucoma.

Purpose: Prostaglandin-associated periorbitopathy in patients with glaucoma is reportedly not caused by EP2 agonist, but it has been a cosmetic problem with prostaglandin F receptor (FP) agonists. In this study, patients with prostaglandin-associated periorbitopathy on FP agonists were switched to EP2 agonist and changes were investigated. Methods: Patients complaining of prostaglandin-associated periorbitopathy were included. The FP agonist was switched to EP2 agonist (omidenepag isopropyl), and patients were followed up for 7 months. Frontal photographs were taken at every visit, and objective changes in deepening of the upper eyelid sulcus were assessed by three observers. Subjective questionnaires (self-awareness of deepening of the upper eyelid sulcus, eyelid/peri-eyelid skin pigmentation, eyelash elongation, and conjunctival hyperemia) were acquired at the start and the endpoint. Factors associated with the change of prostaglandin-associated periorbitopathy were investigated using logistic regression analysis. Results: Included were 23 eyes of 23 patients (17 women; 60.6 years). At 7 months, objective deepening of the upper eyelid sulcus improved by 76%. The subjective questionnaires showed that deepening of the upper eyelid sulcus improved in 95%, eyelid/peri-eyelid skin pigmentation in 76%. The less extent of myopia was a significant factor in the eyes with improved eyelid/peri-eyelid skin pigmentation. After switching, no change in intraocular pressure or visual acuity was observed (P ≥ 0.22). Conclusion: Switching to omidenepag isopropyl increased patient satisfaction and might be the first step to lightening deepening of the upper eyelid sulcus and eyelid/peri-eyelid skin pigmentation. It was suggested that pigmentation may be more easily improved in nonmyopic eyes.

Efficacy and Safety of Omidenepag Isopropyl 0.002% Ophthalmic Solution: A Retrospective Analysis of Real-World Data in Japan.

INTRODUCTION: This study aimed to clarify the efficacy and safety of omidenepag isopropyl (OMDI) in a retrospective, real-world, multicenter setting. METHODS: A retrospective medical chart review of patients with glaucoma and ocular hypertension receiving OMDI from November 2018 to November 2019 with at least 12 weeks of follow-up was conducted in 11 eye clinics in Japan. The participants were categorized into three therapy groups, designated the naïve monotherapy, switching monotherapy, and concomitant therapy groups. The main outcome measures were the change in intraocular pressure (IOP) at week 4 and week 12 after the initiation of OMDI treatment, and frequency of adverse drug reactions. RESULTS: Data were collected from 827 patients. The baseline IOP in the naïve group was 16.6 ± 4.2 mmHg. The mean IOP reduction at week 4 and week 12 was - 2.9 ± 3.2 mmHg (P < 0.0001) and - 2.5 ± 2.9 mmHg (P < 0.0001), respectively. Eyes with baseline IOP less than 16 mmHg also showed a significant reduction of IOP of - 1.4 ± 2.0 mmHg at week 12. OMDI significantly reduced IOP not only in eyes with primary open-angle glaucoma but also in eyes with primary angle-closure glaucoma and secondary glaucoma. In the switching monotherapy group, IOP did not change significantly after switching from most classes of medications to OMDI, but further IOP reduction was observed in the case of switching from beta-blockers to OMDI. The frequency of adverse drug reactions was 14.1% in all participants, and the most common adverse reaction was ocular hyperemia (7.6%). No serious and severe side effects were observed in this study. CONCLUSION: OMDI showed an IOP-lowering effect in eyes with various types of glaucoma and using various therapeutic regimens in real-world clinical practice. In addition, OMDI did not show any serious and severe side effects, suggesting the potential of OMDI as a first-line medicine for the treatment of glaucoma. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN): 000040040.

Recovery of deepening of the upper eyelid sulcus after switching from prostaglandin FP receptor agonists to EP2 receptor agonist: a 3-month prospective analysis.

PURPOSE: To examine the effect of switching from a prostanoid FP receptor agonists to EP2 receptor agonist (omidenepag isopropyl) on the deepening of the upper eyelid sulcus (DUES) and intraocular pressure (IOP) in Japanese glaucoma patients over 3 months post treatment. STUDY DESIGN: Prospective observational study. METHODS: Patients with glaucoma who received FP receptor agonists treatment and had complained of DUES-related reduction in quality of life were included. Their FP receptor agonists was switched to omidenepag isopropyl without a drug holiday. At baseline and 1 and 3 months post-switch, photographs were taken and the changes in DUES were assessed by three independent observers. IOP and adverse events were also assessed. RESULTS: The study included 23 eyes of 23 patients (6 men, 17 women; average age, 60.6 years). After switching, DUES improved in 12 eyes at 1 month and in 16 eyes at 3 months; eyes in the remaining patients showed no worsening of the condition. The mean IOP before switching was 15.3 ± 3.3 mmHg (95% confidence interval 13.9-16.7 mmHg). Following the switch, the mean IOP values were 15.6 ± 3.3 mmHg (14.1-17.0 mmHg) at 1 month and 15.5 ± 3.3 mmHg (14.1-16.9 mmHg) at 3 months (P = 1.0 at 1 month, P = 1.0 at 3 months; both adjusted by Bonferroni correction). No adverse effects were observed. CONCLUSION: Omidenepag isopropyl improved DUES while maintaining IOP in over 70% of Japanese patients with glaucoma who exhibited DUES caused by FP receptor agonists; the improvement was observed within 3 months after switching from FP receptor agonists.

Effects of French maritime pine bark/bilberry fruit extracts on intraocular pressure for primary open-angle glaucoma.

We tested oral French maritime pine bark (40 mg)/bilberry fruit extract (90 mg) supplements for intraocular pressure-lowering effects in Japanese subjects with primary open-angle glaucoma. Eighteen subjects (29 eyes) were recruited with intraocular pressure of ≥15 mmHg who used one to three bottles of antiglaucoma medications. After a 2-week observation (period 1), subjects ingested a tablet/day of Sante® Glagenox for 4 weeks (period 2). The mean intraocular pressure (17.2 ± 2.3 mmHg) decreased significantly to 15.7 ± 1.9 mmHg (8.7% reduction) at week 4 (p = 0.0046). The mean morning intraocular pressure (14.1 ± 3.1 mmHg) self-measured using the iCare HOME tonometer during period 1 decreased significantly to 13.3 ± 2.9 mmHg (5.7% reduction) during period 2 (p = 0.0291). Blood redox parameters, diacron reactive oxygen metabolites, biologic antioxidant potential, and sulfhydryl tests were unchanged after 4-week supplementation. Intra-subject comparisons, compared to period 1, showed pooled, self-measured, period-2 intraocular pressures was significantly lower in nine subjects (50%), unchanged in six subjects (33%), and elevated in three subjects (17%), suggesting some non-responders. Four-week supplementation with French maritime pine bark/bilberry fruit extracts can further reduce intraocular pressure even in Japanese patients with controlled primary open-angle glaucoma. Further study should confirm the intraocular pressure-lowering effects and mechanisms of this supplement in glaucoma management. The study was registered in UMIN (ID: UMIN000033200).

Preperimetric Glaucoma Prospective Study (PPGPS): Predicting Visual Field Progression With Basal Optic Nerve Head Blood Flow in Normotensive PPG Eyes.

PURPOSE: To investigate the site specificity of visual field changes in eyes with normotensive preperimetric glaucoma (PPG), and to determine factors influencing visual field progression. METHODS: This prospective study comprised 84 eyes of 84 normotensive PPG patients followed for at least 16 months. Optic nerve head (ONH) blood flow was assessed with tissue-area mean blur rate (MBRT), derived from laser speckle flowgraphy. Total deviation (TD) was measured in each sector of the Garway-Heath map to evaluate the site specificity of visual field loss. Subjects with a TD slope in the first quartile were classified as progressive, and other subjects as nonprogressive. Linear and multiple regression analyses were performed to determine factors affecting visual field progression. RESULTS: TD in the superior sector significantly decreased in the subjects overall during the follow-up periods (-0.48 ± 1.92 dB/y, P = 0.025). Linear regression analysis showed that basal MBRT-inferior was correlated significantly with TD-superior slope (r = 0.332, P = 0.002). Furthermore, basal MBRT was significantly lower in this sector in the progressive than the nonprogressive group (P = 0.010). Multiple linear regression analysis revealed that basal MBRT-inferior was the only predictive factor for TD-superior slope (ß = 0.329, P = 0.005). CONCLUSIONS: These findings suggest that superior-sector visual field progression is most common in normotensive PPG eyes, and that reduced basal ONH blood flow is associated with visual field progression. TRANSLATIONAL RELEVANCE: These findings provide new insight into the involvement of ONH blood flow impairment in glaucoma pathogenesis, and demonstrate the importance of assessing ONH blood flow to determine visual field progression in normotensive PPG.

Preperimetric Glaucoma Prospective Observational Study (PPGPS): Design, baseline characteristics, and therapeutic effect of tafluprost in preperimetric glaucoma eye.

PURPOSE: There is no consensus on the diagnosis or treatment policy for Preperimetric Glaucoma (PPG) because the pathogenesis of PPG is not clear at this time. Preperimetric Glaucoma Prospective Observational Study (PPGPS) is a first multicenter, prospective, observational study to clarify the pathogenesis of PPG. This article indicates study design, patient baseline characteristics, and analysis focused on optic nerve head (ONH) blood flow in PPG, as well as the intraocular pressure (IOP) -lowering effect and ONH blood flow-improving effects of Tafluprost. METHOD: In this study, 122 eyes from 122 subjects (mean age: 53.1 ± 14.3) newly diagnosed as PPG were enrolled. The circumpapillary retinal nerve fiber layer thickness (cpRNFLT) was evaluated with optical coherence tomography (OCT). The ONH blood flow was measured with laser speckle flowgraphy. The therapeutic effect of Tafluprost was evaluated at Month 0 (ONH blood flow-improving effect) and Month 4 (IOP-lowering effect). RESULTS: The untreated IOP, cpRNFLT, and baseline Mean deviation (MD) value was 16.4 ± 2.5 mmHg, 80.4 ± 8.2 µm, and -0.48 ± 1.29 dB, respectively. In the site-specific visual field evaluation using the sector map, there was no appreciable site-specific visual field defect in the eye with PPG. The inferior region of cpRNFLT in 4-quadrant OCT sector analysis and 6 o'clock region in 12-o'clock OCT sector analysis was the highest rate of abnormality in PPG eyes. Topical administration of Tafluprost significantly reduced IOP from 16.4 ± 2.5 mmHg at baseline to 14.5 ± 2.3 mmHg at Month 4 (P < 0.001, paired t-test). In the linear regression analysis, there was a significant relationship between the increase of ONH blood flow and baseline value. CONCLUSION: PPGPS is a first prospective study focusing on the pathology of PPG. This study is expected to elucidate the pathology of PPG, with evidence useful for determining a treatment strategy for PPG.