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[Purpose] To investigate the effectiveness of screening and subsequent intervention for age-related macular degeneration (AMD) in Japan. [Study design] Best-case-scenario analysis using a Markov model. [Methods] The clinical effectiveness and cost-effectiveness of screening for AMD were assessed by calculating the reduction proportion of blindness and the incremental cost-effectiveness ratio (ICER). The Markov model simulation began at screening at the age of 40 years and ended at screening at the age of 90 years. The first-eye and second-eye combined model assumed annual state-transition probabilities in the development and treatment of AMD. Data on prevalence, morbidity, transition probability, utility value, and treatment costs were obtained from previously published reports. Sensitivity analysis was performed to assess the influence of the parameters. [Results] In the base-case analysis, screening for AMD every 5 years, beginning at age 40 years and ending at age 74 years (reflecting the screening ages of the current Japanese legal “Specific Health Checkups”) showed a decrease of 40.7% in the total number of blind patients. The screening program reduced the number of blind people more than did the additional AREDS/AREDS2 formula supplement intake. However, the ICER of screening versus no screening was ¥9, 846, 411/QALY, which was beyond what people were willing to pay (WTP) in Japan. Sensitivity analysis revealed that neither OCT nor AI improved the ICER, but the scenario in which the prevalence of smoking decreased by 30% improved the ICER (¥4, 655, 601/QALY) to the level under the WTP. [Conclusions] Ophthalmologic screening for AMD is highly effective in reducing blindness but is not cost-effective, as demonstrated by a Markov model based on real-world evidence from Japan.

The optical properties of 2,5-diamino-3,6-dicyanopyrazine derivatives bearing singly methyl- or halogen-substituted benzyl groups were studied in both solution and crystalline phases. In solution, all derivatives showed similar absorption and fluorescence properties, since the electronic state of their fluorophore was not altered by substituents attached to the benzyl groups. In contrast, crystalline compounds exhibited a variety of fluorescence colours (yellow, orange, and red), since their solid-state absorption and fluorescence properties were correlated with a change in the electron-donating ability of amino groups due to crystallisation. The absolute fluorescence quantum yields of crystalline dyes (0.14–0.91) showed broad variability, depending on the nature and positions of terminal substituents.

The crystal structures of the ortho-X-benzyl derivatives, where X=F, Cl, Br, I, and Me, of 2,5-bis(N,N-dibenzylamino)-3,6-dicyanopyrazine dyes (C34H24N6X4) were analysed to evaluate the effect of a systematic series of structures on the occurrence of polymorphism. Detailed crystal structure analysis indicated that the thermally stable forms of the polymorphic derivatives (Cl and Br derivatives) were close-packed, whereas those of the non-polymorphic derivatives (F and I derivatives) were stabilised by an intermolecular interaction involving the ortho-substituents. In the thermally metastable forms of the polymorphic derivative, halogen-halogen and halogen-nitrogen interactions contributed to the stabilisation of these crystals in the same way as the thermally stable form of the non-polymorphic derivatives. This indicated that the ease of polymorph occurrence would require an appropriate balance between the crystal energy of the close-packed structure and that of the crystal structure generated mainly by the electrostatic interactions involving the halogens in these halogenated pyrazine derivatives. In addition, the similar tendency of the occurrence of polymorphs in these halogenated pyrazine derivatives was found in 19 sets of halogenated compounds having known crystal structures of F, Cl, Br and I derivatives including at least one polymorphic derivative in the crystal structure database.

Polymorphism-dependent fluorescence, a phenomenon in which a compound shows various fluorescence properties among its polymorphs, contributes to understanding the relationship between the crystal structure and solid-state fluorescence properties. Here we report a variety of solid-state fluorescence efficiencies brought about by benzyl groups in polymorphs of an organic pyrazine dye, where the polymorphs showed quite different fluorescence efficiencies (fluorescence quantum yield: 14% vs. 64%) despite their similar molecular conformations and packing motifs in the crystal structures. Crystal structure analysis and optical measurements revealed that local loose packing caused by the benzyl groups, which are not a part of the pyrazine fluorophore, greatly influenced the fluorescence efficiency in the polymorphs. This result showed that a benzyl substituent can be used as an effective molecular modification for tuning solid-state fluorescence efficiency.

A metal-free pyrazine dye exhibited vapoluminescence when exposed to benzene vapour. Single-crystal X-ray analysis revealed that its flexible bulky groups and weak interactions involving halogens play an essential role in the occurrence of the observed vapoluminescence.

Conformational polymorphism of a series of 2,5-bis(N,N-dibenzylamino)-3,6-dicyanopyrazine dyes, with high molecular flexibility in a non-hydrogen-bonding system, is described. Three derivatives having a substituent at the 4-position of the benzyl groups exhibited several crystal forms with different colours (red, orange, and yellow), whereas a single form was found in the unsubstituted benzyl derivative and the derivative containing 2-naphthylmethyl groups. The effects of conformational flexibility and the substituents on conformational polymorphism were evaluated through structural, energetic, and statistical analyses based on all of the observed crystal structures. They were divided into four conformational groups according to their conformational similarities, and the major difference among the groups was attributed to the amino geometry. Statistical research using the Cambridge Structure Database suggested that a dibenzylamino group connected to an aromatic ring had a suitable potential surface for the occurrence of conformational polymorphs, and had at least two potential wells with respect to the amino geometry. This result revealed that the flexibility of the dibenzylamino group in the pyrazine derivatives enabled the formation of various molecular shapes. However, the preference of occurrence of polymorphs was different in these derivatives. Crystal structure analysis indicated that the similarity in the molecular shapes was significant for the closed packing in the thermally stable forms, whereas the terminal substituents on the dibenzyl groups played an important role in the crystal structures of the thermally metastable forms via the formation of weak interactions such as halogen interactions.

Purpose: This study was performed to determine the levels of lipids deposited on in vivo worn silicone hydrogel lenses. Methods: Three silicone hydrogel materials, galyfilcon A, senofilcon A, and asmofilcon A, were worn for 2 weeks by 35 normal subjects. Total lipid deposition was determined by the sulfo-phospho-vanillin reaction. Cholesterol was estimated by a colorimetric probe through enzymatic oxidation. Phospholipid level was estimated by determining phosphorus with ammonium molybdate through enzymatic digestion. Results: The total lipid content recovered from galyfilcon A, senofilcon A, and asmofilcon A was 32.9 ± 33.8, 42.1 ± 14.0, and 36.6 ± 31.9 μg/lens, respectively. The cholesterol content recovered from galyfilcon A, senofilcon A, and asmofilcon A was 26.2 ± 26.9, 28.6 ± 19.4, and 31.1 ± 21.1 μg/lens, respectively. There were no statistically significant differences in total lipids and cholesterol among the contact lens types. However, the quantity of phospholipid recovered from the asmofilcon A (7.0 ± 5.5 μg/lens) lenses was significantly higher than from galyfilcon A (1.1 ± 0.8 μg/lens) and senofilcon A (2.4 ± 0.8 mg/lens) lenses (p < 0.05, Mann-Whitney test). Conclusions: The quantity of total lipid and cholesterol deposited on the 3 silicone hydrogel lenses tested did not differ. However, there were significant differences in the amounts of phospholipid deposited among the 3 silicone hydrogel lenses, of which clinical significance should be explored in the future study.

Purpose The Na(+)-/K(+)-dependent ATPase (Na,K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. The role of insulin in the regulation of Na,K-ATPase activity and pump function in corneal endothelial cells was investigated. Methods Confluent monolayers of mouse corneal endothelial cells were exposed to insulin. ATPase activity was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate; Na,K-ATPase activity was defined as the portion of total ATPase activity sensitive to ouabain. Pump function was measured with the use of a Ussing chamber; pump function attributable to Na,K-ATPase activity was defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis and immunocytochemistry were performed to measure the expression of the Na,K-ATPase alpha(1)-subunit. Results Insulin increased the Na,K-ATPase activity and pump function of cultured corneal endothelial cells. These effects were blocked by protein kinase C (PKC) inhibitors and protein phosphatases 1 and 2A inhibitor. Western blot analysis indicated that insulin decreased the ratio of the inactive Na,K-ATPase alpha(1)-subunit. Immunocytochemistry indicated that insulin increased the cell surface expression of the Na,K-ATPase alpha(1)-subunit. Conclusions These results suggest that insulin increases the Na,K-ATPase activity and pump function of cultured corneal endothelial cells. The effect of insulin is mediated by PKC and presumably results in the activation of PP1, 2A, or both, which are essential for activating Na,K-ATPase by alpha(1)-subunit dephosphorylation.