Efficacy, durability, and safety of faricimab up to every 16 weeks in patients with neovascular age-related macular degeneration: 2-year results from the Japan subgroup of the phase III TENAYA trial.

PURPOSE: To evaluate 2-year efficacy, durability, and safety of faricimab in the TENAYA Japan subgroup and pooled global TENAYA/LUCERNE cohort of patients with neovascular age-related macular degeneration (nAMD). METHODS: Subgroup analysis of TENAYA/LUCERNE (NCT03823287/NCT03823300): phase III, multicentre, randomised, active comparator-controlled, double-masked, non-inferiority trials. Treatment-naïve patients aged ≥ 50 years with nAMD were randomised (1:1) to intravitreal faricimab (6.0 mg up to every 16 weeks [Q16W] after 4 initial Q4W doses) or aflibercept (2.0 mg Q8W after 3 initial Q4W doses). Outcomes were assessed through year 2 for the TENAYA Japan subgroup (N = 133) and global pooled TENAYA/LUCERNE cohort (N = 1329). RESULTS: Vision and anatomic improvements achieved with faricimab at year 1 were maintained over 2 years and were generally comparable between the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Adjusted mean best-corrected visual acuity (BCVA) change from baseline at year 2 for the TENAYA Japan subgroup and global pooled TENAYA/LUCERNE cohort was +7.1 (3.7-10.5) and +4.4 (3.2-5.5) letters in the faricimab arm, respectively, and +5.2 (1.9-8.6) and +4.3 (3.1-5.4) letters in the aflibercept arm, respectively. At week 112, the proportion of faricimab-treated patients on Q16W dosing was 61.0% and 63.1% in the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Faricimab was well tolerated through year 2. CONCLUSION: Year 2 TENAYA Japan subgroup findings for faricimab were generally consistent with the pooled global TENAYA/LUCERNE results in patients with nAMD. Vision and anatomical benefits with faricimab were similar to those with aflibercept but with fewer injections.

Six-month outcomes of switching from aflibercept to faricimab in refractory cases of neovascular age-related macular degeneration.

PURPOSE: To assess 6-month outcomes of switching from aflibercept to faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) previously requiring monthly injections. METHODS: This multicenter retrospective study examined nAMD eyes receiving monthly aflibercept injections switched to faricimab administered monthly up to 4 injections followed by injections at a minimum of 2-month intervals as per drug labeling. Data regarding age, sex, number of previous injections, treatment intervals, and best-corrected visual acuity (BCVA) were collected. Central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and maximal pigment epithelial detachment (PED) height were measured by optical coherence tomography. RESULTS: The study included 130 eyes of 124 patients. At 6 months, 53 eyes (40.8%) continued on faricimab treatment (Group 1), while 77 eyes (59.2%) discontinued faricimab for various reasons (Group 2) the most common being worse exudation. There were no significant differences between the two groups at baseline. In Group 1, CRT and SFCT significantly decreased at 1 month (P = 0.013 and 0.008), although statistical significance was lost at 6 months (P = 0.689 and 0.052). BCVA and maximal PED height showed no significant changes; however, mean treatment intervals were extended from 4.4 ± 0.5 weeks at baseline to 8.7 ± 1.7 weeks at 6 months (P < 0.001) in Group 1. No clear predictors of response were identified. CONCLUSION: Switching from aflibercept to faricimab allowed for extension of treatment intervals from monthly to bimonthly in roughly 40% of eyes, suggesting that faricimab may be considered in refractory nAMD cases.

INCIDENCE AND RISK FACTORS OF INTRAOCULAR INFLAMMATION AFTER BROLUCIZUMAB TREATMENT IN JAPAN: A Multicenter Age-Related Macular Degeneration Study.

PURPOSE: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan. METHODS: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors. RESULTS: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset. CONCLUSION: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.

SCLERAL THICKNESS IN THE FELLOW EYES OF PATIENTS WITH UNILATERAL CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: The sclera is reportedly thicker in eyes with central serous chorioretinopathy (CSC) than in healthy control eyes. We compared the scleral thicknesses of the affected and unaffected fellow eyes of patients with unilateral CSC. METHODS: We retrospectively examined the findings of 115 patients with unilateral CSC. Comparisons of the spherical equivalent, axial length, anterior chamber depth, subfoveal choroidal thickness, scleral thickness, and presence of peripheral ciliochoroidal effusion of the affected and fellow eyes were made. Using anterior segment optical coherence tomography, scleral thickness was measured vertically, 6 mm posterior to the scleral spur in the superior, temporal, inferior, and nasal directions. RESULTS: No significant differences in scleral thickness in all four directions, spherical equivalent, axial length, anterior chamber depth, and frequency of ciliochoroidal effusion were found between the affected and unaffected fellow eyes. The only significant difference between the affected and fellow eyes was observed in the subfoveal choroidal thickness (398.8 µ m vs. 346.6 µ m, P < 0.001). CONCLUSION: A thickened choroid seems to have a direct effect on CSC development. By contrast, the affected and fellow eyes showed no significant difference in scleral thickness, indicating that scleral thickening may be a predisposing factor for the development of CSC.

Subfoveal choroidal thickness after brolucizumab therapy for neovascular age-related macular degeneration: a short-term multicenter study.

BACKGROUND/PURPOSE: Observation of choroidal thickness after anti-vascular endothelial growth factor (VEGF) therapy may be important for the ideal management of neovascular age-related macular degeneration (AMD). This study investigated changes in subfoveal choroidal thickness (SCT) during loading doses of intravitreal injections of brolucizumab in eyes with neovascular AMD. METHODS: This study included 73 eyes of 72 patients with neovascular AMD at five university hospitals in Japan. All 73 eyes underwent three monthly 6.0 mg intravitreal injections of brolucizumab at baseline, 1 month, and 2 months. The SCT at 3 months was evaluated using optical coherence tomography. RESULTS: The 73 eyes were classified into the treatment-naïve group (43 eyes) and the switched group (30 eyes) that were switched from other anti-VEGF treatments. After three intravitreal injections of brolucizumab, SCT significantly decreased from 236.5 ± 98.8 µm at baseline to 200.4 ± 98.3 µm at 3 months (percent of baseline 84.7%, P < 0.001) in the treatment-naïve group. In the switched group, SCT also significantly decreased from 229.0 ± 113.2 µm at baseline to 216.9 ± 110.2 µm at 3 months (percent of baseline 94.7%, P = 0.039), although the decrease was not as marked compared to that of the treatment-naïve group. CONCLUSION: Intravitreal injections of brolucizumab for neovascular AMD significantly reduced the SCT in both the treatment-naïve and switched groups. Brolucizumab may cause significant anatomic changes in the choroid, particularly in treatment-naïve AMD eyes, possibly more than that previously reported for other anti-VEGF agents.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS OF CLASSIC CHOROIDAL NEOVASCULARIZATION IN POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To evaluate the flow signals in subretinal hyperreflective material (SHRM) that represents classic choroidal neovascularization (CNV) on fluorescein angiography in eyes with polypoidal choroidal vasculopathy. METHODS: We retrospectively reviewed 20 eyes with polypoidal choroidal vasculopathy that appeared to have classic CNV on fluorescein angiography, accompanied by SHRM on optical coherence tomography (OCT) at the same location. Using OCT angiography (OCTA), we analyzed intrinsic flow signals in the SHRM (cross-sectional B-scans and en face). The possible association between pretreatment OCT angiography findings and fibrotic scar formation after antivascular endothelial growth factor (VEGF) treatment was evaluated. RESULTS: Six of 20 eyes (30%) showed vascular SHRM; the remaining 14 eyes (70%) showed avascular SHRM at the classic CNV site at baseline. The SHRM corresponded with polypoidal lesions seen on indocyanine green angiography in 5 of 6 eyes with vascular SHRM and in all 14 eyes with avascular SHRM. After anti-VEGF treatment, all 6 eyes with vascular SHRM left a fibrotic scar, whereas all 14 eyes with avascular SHRM showed no scar formation (P < 0.001). CONCLUSION: Using OCT angiography, we evaluated the flow signals in SHRM that represented classic CNV in eyes with polypoidal choroidal vasculopathy and successfully differentiated true Type 2 macular neovascularization from pseudo classic CNV.

CILIOCHOROIDAL EFFUSION IN CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To investigate the prevalence of ciliochoroidal effusion (CE) in central serous chorioretinopathy (CSC) using anterior-segment optical coherence tomography and its association with the clinical features of CSC. METHODS: Overall, 164 eyes of 164 patients with CSC and 51 eyes of 51 age- and sex-matched normal control participants were retrospectively examined. Anterior-segment optical coherence tomography was used to assess patients with CSC and control subjects for CE and scleral thickness. Central serous chorioretinopathy eyes were divided into two groups: eyes with CE (CE group) and eyes without CE (non-CE group). Scleral thickness was measured at the point that was 6 mm posterior to the scleral spur in four directions. RESULTS: Among the 164 eyes with CSC, 32 eyes (19.5%) displayed CE, and this proportion was significantly higher than that in control subjects (2.0%) (P = 0.001). Scleral thickness was significantly greater in the CE group compared with the non-CE group at all four directions (P < 0.05 for all). Multivariable analysis revealed that the mean scleral thickness (odds ratio: 1.01; 95% confidence interval: 1.00-1.02; P = 0.007) was significantly associated with the incidence of CE. CONCLUSION: Central serous chorioretinopathy may accompany fluid accumulation in the anterior segment more frequently than previously expected in association with thick sclera.

Retrospective exploratory analyses on gender differences in determinants for incidence and progression of diabetic retinopathy in Japanese patients with type 2 diabetes mellitus.

Gender differences in risks for macrovascular complications in type 2 diabetes mellitus (T2DM) have been well established. However, the impact of gender differences on diabetic retinopathy (DR) has not been fully elucidated. We therefore retrospectively explored gender-specific determinants for DR in patients with T2DM in a small sized Japanese cohort in Okinawa. There were 214 patients who were diagnosed as no DR (n = 142) and non-proliferative DR (n = 72) in 2009. During the follow-up of median 7 years, 41/142 of incidence, 26/72 of progression, and 67/214 of incidence and progression were observed, respectively. DR was assessed using the modified international clinical DR severity scales. The risks for incidence, progression as well as incidence and progression of DR were comparable between men and women, respectively. Cox proportional hazard models in multivariate analyses demonstrated that the only common determinant in both men and women for DR was the duration of T2DM. Regarding gender-specific determinants, lower level of serum albumin in men as well as higher HbA1c, lower level of estimated glomerular filtration rate, and lower level of serum uric acid in women were extracted, respectively. Although precise mechanisms for such gender-specific determinants of DR still remain unsolved, the present study would highlight a couple of factors associated with gender-specific determinants for DR in a limited numbers of Japanese cohort. Prospective observational studies on gender-specific determinants of DR in a large scale cohort are warranted to further clarify underlying mechanisms.

Temporary changes of visual outcomes and anterior chamber parameters after phacoemulsification and low-add-power segmented intraocular lens implantation for primary angle closure disease.

PURPOSE: To evaluate the temporary changes in visual outcomes and anterior segment parameters after cataract surgery plus low-add bifocal intraocular lens (IOL) implantation for primary angle closure disease (PACD). METHODS: This retrospective comparative case-control study included two groups: low-add-power segmented IOL and monofocal IOL. Postoperative examination involved evaluation of uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), uncorrected intermediate visual acuity (UIVA), and spherical equivalent (SE). Anterior segment examination was performed using anterior segment optical coherence tomography. RESULTS: This study included 19 eyes of 11 consecutive patients who underwent cataract surgery. The low-add group had better UDVA than the monofocal group at 3 months postoperatively, better UIVA at 1 month postoperatively, better UNVA at 1 week postoperatively. In the low-add group, SE increased at 1 and 3 months postoperatively compared with 1 week postoperatively. In the monofocal group, objective SE decreased at 1 and 3 months postoperatively compared with 1 week postoperatively. In the low-add group, the anterior chamber depth (ACD) became significantly deep gradually at 1 and 3 months compared with at 1 week postoperatively. In the monofocal group, the ACD became significantly shallow gradually at 1 and 3 months than at 1 week postoperatively. CONCLUSION: The low-add-power segmented IOL achieved better far and intermediate distance visual acuity after cataract surgery in PACD patients than did the monofocal IOL. The ACD became deeper and SE showed a hyperopic shift with the low-add-power segmented IOL at 1 and 3 months after cataract surgery compared with at 1 week after cataract surgery.

QUANTIFICATION OF CHOROIDAL VASCULATURE BY HIGH-QUALITY STRUCTURE EN FACE SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY IMAGES IN EYES WITH CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To determine the density of the choroidal vasculature by high-quality structure en face optical coherence tomography (OCT) scanned at the same time as OCT angiography in eyes with central serous chorioretinopathy (CSC). METHODS: Thirty-five eyes of 30 patients with CSC (20 men and 10 women; average age, 48.4 years) were studied. Volume scans (12 × 12 mm-square) were obtained at the same time as OCT angiographic scans (Plex Elite 9000; Swept-Source OCT, Zeiss). High-quality structure en face images were flattened at Bruch membrane and binarized to identify and quantify the choroidal vascular density by the Bernsen method of the segmentation slab of one-half of the choroidal thickness. Similarly, high-quality structure en face choroidal images of 35 healthy eyes of 29 patients (18 men and 11 women; average age, 51.7 years) were binarized and analyzed as controls. The en face images were cropped to exclude the optic disk. RESULTS: The mean cropped image size was 9.57 mm × 9.57 mm in the eyes with CSC and 9.48 mm × 9.48 mm in the healthy eyes (P = 0.41). In the eyes with CSC, the choroidal vascular density was 61.6 ± 7.5% of the choroid, which was significantly greater than that in the healthy eyes at 49.4 ± 7.5% (P < 0.01). CONCLUSION: High-quality structure en face OCT can be used to assess the density of the choroidal vessels quantitatively and noninvasively in eyes with CSC.

CLINICAL FINDINGS OF EYES WITH MACULAR EDEMA ASSOCIATED WITH BRANCH RETINAL VEIN OCCLUSION REFRACTORY TO RANIBIZUMAB.

PURPOSE: To determine the relationship between the clinical findings and the response to ranibizumab therapy in eyes with macular edema associated with branch retinal vein occlusion. METHODS: We reviewed the medical records of 68 patients with macular edema associated with a branch retinal vein occlusion. The patients were placed in the refractory group if the central foveal thickness remained more than 250 µm throughout the 6-month study period despite the ranibizumab therapy; otherwise, they were placed in the responsive group. RESULTS: Sixty (88.2%) of 68 eyes were placed in the responsive group and the other 8 eyes (11.8%) were placed in the refractory group. At the pretreatment examination, fluorescein angiography showed extensive leakage from occluded vessels in 52 (86.7%) of the 60 eyes in the responsive group and focal leakages from microaneurysms or dilated capillaries in the other 8 eyes (13.3%). In the refractory group, 7 (87.5%) of 8 eyes had only focal leakage and 1 eye (12.5%) had extensive leakage (P < 0.0001). The mean initial subfoveal choroidal thickness in the eyes with branch retinal vein occlusion in the responsive group was significantly thicker than that in the fellow eyes (278.0 ± 90.5 µm, 249.9 ± 94.4 µm; P < 0.0001). On the other hand, the mean initial subfoveal choroidal thickness in the refractory group was not significantly different from that of the fellow eyes (P = 0.4002). CONCLUSION: The dye leakage pattern in the fluorescein angiography images and choroidal thickness may be associated with response to ranibizumab therapy.

A Cell-Targeted Non-Cytotoxic Fluorescent Nanogel Thermometer Created with an Imidazolium-Containing Cationic Radical Initiator.

A cationic fluorescent nanogel thermometer based on thermo-responsive N-isopropylacrylamide and environment-sensitive benzothiadiazole was developed with a new azo compound bearing imidazolium rings as the first cationic radical initiator. This cationic fluorescent nanogel thermometer showed an excellent ability to enter live mammalian cells in a short incubation period (10 min), a high sensitivity to temperature variations in live cells (temperature resolution of 0.02-0.84 °C in the range 20-40 °C), and remarkable non-cytotoxicity, which permitted ordinary cell proliferation and even differentiation of primary cultured cells.

CHOROIDAL BLOOD FLOW VISUALIZATION IN HIGH MYOPIA USING A PROJECTION ARTIFACT METHOD IN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To visualize choroidal blood flow in larger vessels in highly myopic eyes using a phenomenon of the projection artifact to in the sclera using optical coherence tomography angiography. METHODS: The retrospective study included 92 eyes (54 patients) with greater than 8 diopters of myopia. All eyes were examined using optical coherence tomography angiography (RTVue XR Avanti; Optovue Inc, Fremont, CA). The blood flow in choroidal vessels was evaluated by attempting to directly segment the choroid and also by placing the segmentation layer behind the choroid, within the sclera. Subfoveal choroidal thickness was also measured at the same time. The authors also evaluated the 54 normal eyes (54 cases) without high myopia as a control group. RESULTS: Segmentation artifacts occurred in 68 cases (73.9%) and precluded direct visualization of the choroidal blood flow in larger vessels. When the segmentation slab was placed posterior to the choroid within the sclera, the choroidal blood flow was visualized in 41 eyes (44.6%). The mean subfoveal choroidal thickness in eyes with visualization of choroidal blood flow was thinner than without visualization (50.3 ± 42.2 µm vs. 100.3 ± 44.4 µm, P < 0.01). Choroidal blood flow in larger vessels was imaged in no control eye. CONCLUSION: The choroidal vessel anatomy could be imaged by detecting flow using the projection artifact in the sclera with optical coherence tomography angiography. This technique may be useful in estimating the vascularity of the choroid.

Lignin-rich enzyme lignin (LREL), a cellulase-treated lignin-carbohydrate derived from plants, activates myeloid dendritic cells via Toll-like receptor 4 (TLR4).

Lignin-carbohydrates, one of the major cell wall components, are believed to be the structures that form chemical linkage between lignin and cell wall polysaccharides. Due to the molecular complexity of lignin-containing substances, their isolation and the assignment of their biological activities have so far remained a difficult task. Here, we extracted two lignin-containing carbohydrates, lignin-rich enzyme lignin (LREL) and pure enzyme lignin (PEL), from barley husk and demonstrated that they act as immune stimulators of dendritic cells (DCs), which are particularly important in linking innate and adaptive immunity. Thioacidolysis, acid hydrolysis, and mild alkali hydrolysis of both LREL and PEL revealed that their immunostimulatory activities depended on the lignin structure and/or content, neutral sugar content (especially the characteristic distribution of galactose and mannose), and presence of an ester bond. Furthermore, we showed that the immunostimulatory potency of the lignin-carbohydrate depended on its molecular weight and degree of polymerization. We also demonstrated that the LREL-induced activation of DCs was mediated via TLR4. Thus, LREL-induced increases in the expression levels of several cell surface marker proteins, production of inflammatory cytokines IL-12p40 and TNF-α, and activation and nuclear translocation of transcription factors, as was observed in the WT DCs, were completely abrogated in DCs derived from the TLR4(-/-) mice but not in DCs derived from the TLR2(-/-), TLR7(-/-), and TLR9(-/-) mice. We further demonstrated that LRELs isolated from other plant tissues also activated DCs. These immunostimulatory activities of lignin-carbohydrates, extracted from edible plant tissues, could have potential relevance in anti-infectious immunity and vaccine adjuvants.

Subfoveal Choroidal Thickness during Aflibercept Therapy for Neovascular Age-Related Macular Degeneration: Twelve-Month Results.

PURPOSE: To investigate changes in subfoveal choroidal thickness after intravitreal aflibercept injections (IAIs) for neovascular age-related macular degeneration (AMD) at 12 months. DESIGN: Retrospective, consecutive, interventional case series. PARTICIPANTS: One hundred forty-four patients with treatment-naïve neovascular AMD examined at 3 university hospitals. METHODS: After a loading phase of 3 monthly 2.0-mg IAIs, the patients were injected bimonthly with additional rescue injections performed for worsening. Subfoveal choroidal thickness in IAI-treated eyes was evaluated using enhanced depth imaging optical coherence tomography (OCT) or swept-source OCT. MAIN OUTCOME MEASURES: Changes in subfoveal choroidal thickness over a 12-month period. RESULTS: Of the 144 treated eyes, 58 (40.3%) had typical neovascular AMD and 86 (59.7%) had polypoidal choroidal vasculopathy (PCV). The mean subfoveal choroidal thickness of treated eyes decreased from 268.1±101.3 µm at baseline to 233.0±99.7 µm at 3 months and remained unchanged at 232.4±99.6 µm at 12 months (percentage decrease, 13.3% at 12 months compared with baseline; P < 0.0001), although there was some fluctuation in between treatments. This decrease in subfoveal choroidal thickness was associated significantly with gain in visual acuity for PCV eyes (P = 0.0087; R = 0.28), but not for eyes with typical neovascular AMD (P = 0.17; R = 0.18). Eyes without persistent or recurrent retinal fluid after the loading phase showed greater decrease in subfoveal choroidal thickness compared with those with persistent or recurrent retinal fluid, in both typical neovascular AMD (P = 0.042) and PCV (P = 0.038) eyes. CONCLUSIONS: Subfoveal choroidal thickness decreased over 12 months with IAI therapy in eyes with neovascular AMD. Changes in subfoveal choroidal thickness after IAIs seem to be related to visual and anatomic outcomes.

One-Year Results of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy.

PURPOSE: To investigate 1-year outcomes of intravitreal aflibercept for polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective, multicenter, consecutive case series. PARTICIPANTS: A total of 90 eyes of 87 patients with treatment-naïve PCV followed at 3 tertiary centers. METHODS: Clinical records were reviewed and imaging studies were analyzed of eyes with PCV that underwent 3 consecutive monthly aflibercept injections followed by injections every 2 months. Additional (rescue) injections were performed for worsening. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and angiographic findings at 1 year. RESULTS: The mean BCVA (logarithm of the minimum angle of resolution units) of the 90 eyes improved from 0.31 at baseline to 0.17 at 12 months (P < 0.001). The mean central retinal thickness decreased from 315 µm at baseline to 204 µm at 12 months (P < 0.001). At 12 months, 64 eyes (71.1%) achieved a dry macula, defined as absence of intraretinal or subretinal fluid on OCT. Of 83 eyes that underwent indocyanine green angiography at both baseline and 12 months, 46 (55.4%) showed complete and 27 (32.5%) showed partial resolution of polypoidal lesions. Eleven of 82 eyes (13.4%) showed decreased size of branching choroidal vascular networks. CONCLUSIONS: Intravitreal aflibercept administered over 1 year improved both visual acuity and macular morphology in a large number of treatment-naïve eyes with PCV.

Development of preparative and analytical methods of the hop bitter acid oxide fraction and chemical properties of its components.

The bitter acids in hops (Humulus lupulus L.) and beer, such as α-, ß-, and iso-α-acids, are known to affect beer quality and display various physiological effects. However, these compounds readily oxidize, and the effect of the oxides on the properties of beer or their potential health benefits are not well understood. In this study, we developed a simple preparative method for the bitter acid oxide fraction derived from hops and designated the constituents as matured hop bitter acids (MHBA). HPLC-PDA-ESI/HRMS and MS(2) revealed that MHBA are primarily composed of α-acid-derived oxides, which possess a common ß-tricarbonyl moiety in their structures similar to α-, ß-, and iso-α-acids. We also developed a quantitative analytical method of whole MHBA by HPLC, which showed high precision and reproducibility. Using our newly developed method, the concentration of whole MHBA in several commercial beers was evaluated. Our results will promote the study of bitter acid oxides.

Effects of tofacitinib on nucleic acid metabolism in human articular chondrocytes.

OBJECTIVE: In our previous screening of chondrocyte protein profiles, the amount of adenosine monophosphate deaminase (AMPD) 2 was found to be decreased by tofacitinib. Extending the study, here we confirmed the decrease of AMPD2 by tofacitinib and further investigated effects of tofacitinib on purine nucleotide metabolism. METHODS: Human articular chondrocytes and a chondrosarcoma cell line: OUMS-27 were stimulated with tofacitinib. Then the levels of AMPD2 and its related enzymes were investigated by Western blot. The levels of AMP and adenosine were assessed by mass spectrometry. RESULTS: We confirmed the significant decrease of AMPD2 by tofacitinib in chondrocytes (p = 0.025). The levels of adenosine kinase and 5'-nucleotidase were decreased in chondrocytes, although they did not meet statistical significance (p = 0.067 and p = 0.074, respectively). The results from OUMS-27 were similar to those from the chondrocytes. The cellular adenosine levels were significantly decreased by tofacitinib in OUMS-27 (p = 0.014). The cellular AMP levels were increased, although they did not meet statistical significance in OUMS-27 (p = 0.066). CONCLUSION: Our data indicate that tofacitinib increases the cellular levels of adenosine, which is known to have anti-inflammatory activity, through the downregulation of AMPD2. This would be a novel functional aspect of tofacitinib.

Subfoveal choroidal thickness in retinal angiomatous proliferation.

PURPOSE: To investigate the subfoveal choroidal thickness in patients with retinal angiomatous proliferation (RAP). METHODS: In consecutive patients with RAP, subfoveal choroidal thickness was retrospectively measured by the use of enhanced depth imaging spectral domain optical coherence tomography in comparison with age-matched control subjects. RESULTS: Nineteen eyes of 19 patients with RAP and 32 eyes of 32 control subjects were included in this study. No significant differences were found between the eyes with RAP and the control eyes regarding age, gender, spherical equivalent, and axial length. Mean subfoveal choroidal thickness in 19 eyes with RAP was significantly less than that in the control eyes (129.5 ± 35.8 µm vs. 201.3 ± 55.0 µm, P < 0.0001). The difference in mean subfoveal choroidal thickness between eyes with Stage 2 RAP (132.8 ± 38.2 µm) and eyes with Stage 3 RAP (126.4 ± 36.6 µm) was not significant, though each measurement was significantly less than that in the control eyes (P < 0.001 and P = 0.002, respectively). CONCLUSION: Eyes with RAP had a significantly thinner subfoveal choroid compared with normal eyes. Such morphologic features may be related to the pathologic mechanism of RAP.