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Koji Nitta,1,2 Gaku Tachibana,1,2 Ryotaro Wajima,1,2 Sachie Inoue,3 Tatsuya Ohigashi,4 Naomi Otsuka,4 Hiroaki Kurashima,4 Kazunori Santo,4 Masayo Hashimoto,4 Hidetoshi Shibahara,3 Mai Hirukawa,3 Kazuhisa Sugiyama2 1Department of Ophthalmology, Fukui-Ken Saiseikai Hospital, Fukui, Japan; 2Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; 3CRECON Medical Assessment Inc., Tokyo, Japan; 4Japan Medical Affairs Group, Santen Pharmaceutical Co., Ltd., Osaka, JapanCorrespondence: Koji Nitta Email nitta.koji7001@fukui.saiseikai.or.jpPurpose: To maintain visual fields and quality of life over a lifetime, medical practice must be conducted taking into consideration not only visual field progression but also future visual field changes that occur over the patients’ expected lifespan. The purpose of this study is to investigate the feasibility of establishing a model that predicts prognosis, estimating the proportion of glaucoma patients with severe visual field defects.Patients and Methods: The data of 191 patients with primary open-angle glaucoma, with a predominance of normal-tension glaucoma, were used for this study. The model was developed based on patients’ backgrounds and risk factors, using Monte Carlo simulation. A “severe visual field defect” was defined as ≤-20 dB. The mean deviation (MD) value for 10,000 virtual patients in each simulation pattern (144 patterns) was calculated using a predictive formula to estimate the MD slope, and the effects of risk factors and intraocular pressure (IOP) reduction on the proportion of patients with severe visual field defects were evaluated.Results: Younger age, later-stage disease, more severe glaucomatous structural abnormalities and the presence of disc hemorrhage were associated with an increase in the progression rate of patients with severe visual field defects. Conversely, lower IOP was associated with a decrease in this rate

Keiji Yoshikawa,1 Kazunori Santo,2 Hiroko Hizaki,2 Masayo Hashimoto2 1Yoshikawa Eye Clinic, Machida, Tokyo, Japan; 2Japan Medical Affairs, Santen Pharmaceutical Co., Ltd, Osaka, Japan Purpose: To quantitatively evaluate the association of intraocular pressure (IOP) reduction with visual field defect (VFD) progression in normal tension glaucoma (NTG) under medical therapy. Patients and methods: Clinical data for 622 eyes of 311 primary open-angle glaucoma and NTG patients were collected from April 2006 to March 2016. Of these patients, those with normal IOP, glaucomatous VFD by Anderson’s criteria, corrected visual acuity ≥0.7, >5 years of medical therapy, ≥5 visual field tests at least five times at 12-month intervals, visual field testing reliability coefficients of ≤33%, and mean deviation (MD) exceeding below -20 dB in the initial visual field test were included in this retrospective data analysis. MD and IOP data were collected at baseline and after 5 years. Following MD categorization into stages I to IV, stage transition matrices were generated using a Markov model to evaluate VFD changes. Eyes were divided based on IOP reduction (0%, 10%, 15%, 20%, 25%, 30%) from baseline. VFD aggravations were compared using the Markov model and MD slopes with IOP reduction rates as cutoff values. Results: Overall, 132 eyes of 132 NTG patients fulfilled the eligibility criteria. MD decreased significantly (P<0.0001) at 5 years vs baseline. During follow-up, visual field stage using the Markov model was constant in ~60%, with transitions in ~40%. IOP decreased significantly (P<0.001) at 5 years vs baseline. Though MD slopes did not differ significantly between each of the groups that achieved the various IOP reduction cut-off values and the corresponding group that did not achieve the cut-off values, a significant difference (P=0.0432) in VFD was found between the group that achie

Keiji Yoshikawa,1 Kazunori Santo,2 Hiroko Hizaki,2 Masayo Hashimoto2 1Yoshikawa Eye Clinic, Tokyo, 2Medical Affairs, Santen Pharmaceutical Co. Ltd., Osaka, Japan Purpose: To analyze factors related to long-term progression of visual field defects (VFD) in patients with normal tension glaucoma (NTG) under medical therapy. Patients and methods: Clinical data from 622 eyes of 311 primary open-angle glaucoma and NTG patients were collected from April 2006 to March 2016. Of these patients, those with normal intraocular pressure (IOP); glaucomatous VFD judged by Anderson’s criteria; corrected visual acuity ≥0.7; receiving more than 6 years medical therapy; having undergone ≥10 visual field tests performed at 6-month intervals using a Humphrey field analyzer (Swedish Interactive Threshold Algorithms standard, C 24-2 program); and having reliability coefficients of visual field testing <33% and mean deviation (MD) more than -20 decibels in the initial visual field test were included in data analysis. The relationship between MD slope deterioration at final observation and consecutive decreases in MD value during the observation period, as well as clinical characteristics and IOP-related factors, were analyzed. Results: Of 134 eyes in 134 NTG patients meeting all eligibility criteria, significant MD slope deterioration was observed in 80 eyes (59.7%). MD slope deterioration was significantly associated with consecutive decreases in MD values (Cochran–Armitage trend test: P=0.0000; univariate logistic regression analysis: P<0.0001). While no significant relationship was observed between central corneal thickness, refractive error, or prevalence of disc hemorrhage, consecutive decreases in MD value was significantly related to MD slope deterioration (univariate logistic regression analysis: P<0.0001). A reduction of IOP during the follow-up period was significantly related to no

Kenji Nakamoto,1 Masahiko Takeshi,2 Toshihiko Hiraoka,2,3 Mayuko Eguchi,2,4 Yuichiro Nakano,1,2 Naomi Otsuka,5 Hiroko Hizaki,5 Hiromi Akai,5 Masayo Hashimoto5 1Department of Ophthalmology, Nippon Medical School, Tokyo, Japan; 2Shinanozaka Clinic, Tokyo, Japan; 3Hiraoka Eye Clinic, Saitama, Japan; 4Musashiurawa Eye Clinic, Saitama, Japan; 5Japan Medical Affairs, Global R&D, Santen Pharmaceutical Co., Ltd., Osaka, Japan Objective: The aim of this study was to evaluate the 24-hour intraocular pressure (IOP)-control effect of the tafluprost/timolol fixed combination (TAF/TIM-FC) in patients with primary open-angle glaucoma after they switched from the concomitant use of tafluprost and timolol gel-forming solution. Patients and methods: Twenty patients with primary open-angle glaucoma (12 male and 8 female; mean ± SD age, 57.0±7.1 years) were included in this study. The patients were treated for 8 weeks with the concomitant administration of tafluprost and timolol gel-forming solution (evening dosing). At the end of this period, the patients underwent 24-hour IOP monitoring (measured at 21:00, 01:00, 05:00, 09:00, 13:00 and 17:00). IOP was measured with Goldmann applanation tonometer (GAT) and Icare PRO at sitting position at all timepoints and additionally, at supine position with Icare PRO tonometer at 01:00 and 05:00. The patients were then all switched to TAF/TIM-FC treatment (evening dosing). After 8 weeks, the 24-hour IOP monitoring was repeated. Results: Nineteen patients completed the study. The mean 24-hour IOPs in the concomitant and TAF/TIM-FC phases were 13.8±2.7 vs 13.3±2.8 mmHg (P=0.0033) with the GAT in the sitting position and 13.96±2.56 vs 13.48±2.56 mmHg (P=0.0120) with the Icare PRO in habitual positions. In comparison with the concomitant phase, significantly lower IOP was observed for the TAF/TIM-FC phase at 21:00 and 01:00 with the GAT and at 01:00 with the Icare PRO.

The version of record of this article, first published in Analytical and Bioanalytical Chemistry, is available online at Publisher’s website: https://doi.org/10.1007/s00216-024-05477-5., Understanding the relationship between the concentration of a drug and its therapeutic efficacy or side effects is crucial in drug development, especially to understand therapeutic efficacy in central nervous system drug, quantifying drug-induced site-specific changes in the levels of endogenous metabolites, such as neurotransmitters. In recent times, evaluation of quantitative distribution of drugs and endogenous metabolites using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) has attracted much attention in drug discovery research. However, MALDI-MSI quantification (quantitative mass spectrometry imaging, QMSI) is an emerging technique, and needs to be further developed for practicable and convenient use in drug discovery research. In this study, we developed a reliable QMSI method for quantification of clozapine (antipsychotic drug) and dopamine and its metabolites in the rat brain using MALDI-MSI. An improved mimetic tissue model using powdered frozen tissue for QMSI was established as an alternative method, enabling the accurate quantification of clozapine levels in the rat brain. Furthermore, we used the improved method to evaluate drug-induced fluctuations in the concentrations of dopamine and its metabolites. This method can quantitatively evaluate drug localization in the brain and drug-induced changes in the concentration of endogenous metabolites, demonstrating the usefulness of QMSI.