Anatomical changes in idiopathic epiretinal membrane at 2-year follow-up assessed using spectral domain optical coherence tomography and optical coherence tomographic angiography.

PURPOSE: To evaluate anatomical changes in the low-stage partial attachment-type idiopathic epiretinal membrane (iERM) over 2 years. METHODS: Data from patients with low-stage partial attachment-type iERM (stage 2) were analyzed. The main outcome measures were anatomical changes, including changes in the foveal avascular zone (FAZ) area, vessel density (VD) in the vascular plexus, and thickness of retinal sublayers during the follow-up period. RESULTS: Thirty patients (mean age: 68±12 years) were included in the study. The FAZ area on the superficial vascular plexus (SVP) significantly decreased from baseline (0.12±0.08 mm2) to month 24 (0.10±0.08 mm2, p=0.024). However, the FAZ area on the deep vascular plexus (DVP) did not significantly decrease from baseline (0.15±0.13 mm2) to month 24 (0.14±0.14 mm2, p=0.099). VDs on both the SVP and DVP did not show significant change from baseline (29.51±8.14% vs. 28.35±5.63%) to month 24 (29.79±9.77%, p=0.564 vs. 28.17±5.75%, p=0.417). Parafoveal ganglion cell and inner plexiform layer (GCIPL) thickness decreased from baseline (108.77±13.61 µm) to month 24 (103.03±15.54 µm, p=0.004). The central total retinal layer thickness did not significantly change from baseline (396.07±64.86 µm) to month 24 (392.04±72.72 µm, p=0.570). CONCLUSION: Even in low-stage ERM, inner retinal changes, including GCIPL thickness, occurred during follow-up periods, which might be owing to degenerative changes or centrifugal movement.

New technology using crystalline lens autofluorescence for presbyopia and cataract grading.

PURPOSE: To investigate whether fundus autofluorescence (FAF) obtained using an ultra-wide field (UWF) fundus camera with an artificial opacity pattern can grade the degree of presbyopia and nuclear cataract. METHODS: Sixty eyes of 30 patients were enrolled in this prospective diagnostic study. The nuclear cataract (nuclear color/opalescence (NC/NO)) was graded according to the Lens Opacity Classification System III. The monocular near point of accommodation (NPA) was measured in eyes with NC3/NO3 or less. The mean gray value difference between the central 8 artificial opacity lesions and peripheral 8 artificial opacity lesions in the retinal AF was measured. The correlation between the mean gray value difference, NPA, and nuclear cataract grade was analyzed. RESULTS: The mean nuclear cataract grade of 60 eyes was 3.2 ± 1.6 and mean NPA of 37 eyes was 45.3 ± 16.1 cm. The mean gray value differences increased with increasing nuclear cataract grade (eyes with NC/NO grade 1, 53.3 ± 11.4; 2, 78.3 ± 13.6; 3, 95.2 ± 12.2; 4, 101.6 ± 11.9; 5, 109.0 ± 22.9; and 6, 121.1 ± 12.0; p < 0.001). The mean gray value difference was positively correlated with both the monocular NPA (R2 = 0.637; ß coefficient = 1.009; 95% CI, 0.748 to 1.271; p < 0.001) and nuclear cataract grade (R2 = 0.661; ß coefficient = 12.437; 95% CI, 10.097 to 14.778; p < 0.001). CONCLUSIONS: The FAF camera with an artificial opacity pattern attached can be used to effectively diagnose the degree of presbyopia and nuclear cataract.

Cut-Off Value of Voluntary Peak Cough Flow in Patients with Parkinson's Disease and Its Association with Severe Dysphagia: A Retrospective Pilot Study.

Background and Objectives. Swallowing and coughing reflexes are both closely associated with airway protection. Peak cough flow (PCF) is associated with dysphagia in several neurogenic diseases. In this study, we aimed to analyze the relationship between PCF and aspiration in Parkinson's disease (PD) and determine the cut-off value of PCF. Materials and Methods. We retrospectively analyzed the records of patients with PD who underwent a videofluoroscopic swallowing study and checked for PCF. A total of 219 patients were divided into an aspiration group (n = 125) and a non-aspiration group (n = 94). Results. Significantly lower PCF values were observed in the aspiration group compared to the non-aspiration group (132.63 ± 83.62 vs. 181.38 ± 103.92 L/min, p < 0.001). Receiver operating characteristic curve analysis revealed that a PCF cut-off value of 153 L/min (area under the receiver operating characteristic curve, 0.648; sensitivity, 73.06%; specificity, 51.06%) was associated with aspiration in PD. Additionally, a univariate analysis showed that the male sex, lower body mass indexes, higher Hoehn and Yahr scales, and PCF values of ≤153 L/min indicated an increased risk of aspiration. Conclusions. Through a multivariate analysis, we demonstrated that a PCF value ≤153 L/min was associated with an increased risk of aspiration (odds ratio 3.648; 1.797-7.407), highlighting that a low PCF is a risk factor for aspiration in patients with PD.

FOVEAL MÜLLER CELL CONE AS A PROGNOSTIC OPTICAL COHERENCE TOMOGRAPHY BIOMARKER FOR INITIAL RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN CYSTOID DIABETIC MACULAR EDEMA.

PURPOSE: To investigate the effect of the foveal Müller cell cone structure on the anatomical and functional response to intravitreal bevacizumab treatment in patients with diabetic macular edema. METHODS: In 93 treatment-naive eyes with center-involved cystic type diabetic macular edema, spectral-domain optical coherence tomography scans of baseline were retrospectively evaluated to determine the foveal Müller cell cone structure and prognostic features including length of disorganization in the retinal inner layers and ellipsoid zone disruption. The area and circularity of the foveal avascular zone of the superficial and deep capillary plexus 1 month after intravitreal bevacizumab treatment were evaluated using optical coherence tomography angiography. RESULTS: Destruction of the foveal Müller cell cone structure and a large foveal avascular zone in the deep capillary plexus (mm2) correlated strongly with a poor anatomical response (CST > 250 µm) at 1 month after first intravitreal bevacizumab (Exp [B] = 29.444, P = 0.002 and Exp [B] = 12.419, P = 0.013, respectively). A destroyed Müller cell cone structure (P = 0.008) and length of ellipsoid zone disruption (P < 0.001) at baseline were associated with poor visual acuity at 1 month after the first intravitreal bevacizumab. CONCLUSION: The foveal Müller cell cone structure correlates with the response to initial antivascular endothelial growth factor treatment.

MORPHOLOGIC AND ANATOMICAL FEATURES OF TYPE 1 MACULAR NEOVASCULARIZATION TRUNKS IN AGE-RELATED MACULAR DEGENERATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To evaluate the morphologic features of macular neovascularization (MNV) trunks at different layers using optical coherence tomography angiography. METHODS: Type 1 MNV trunks in age-related macular degeneration were retrospectively evaluated at the subretinal pigment epithelium and sub-Bruch membrane (subBM) layers. The detectability and location of the trunks were compared. MNV trunks at the subBM layer on optical coherence tomography angiography B-scans were evaluated using a flow overlay. The correlations of the MNV trunk with optical coherence tomography angiography and optical coherence tomography parameters were evaluated. RESULTS: Among the 63 included eyes, 27 showed core vessels at the subretinal pigment epithelium layer and 52 showed MNV trunks at the subBM layer, which were connected with the MNV at the subretinal pigment epithelium layer. The locations of the MNV trunks in each layer were different. MNV trunk types at the subBM layer were related to disease duration, distance from the large choroidal vessels, and MNV vessel density. The large choroidal vessel diameter was correlated with the MNV trunk diameter at the subBM layer. CONCLUSION: Macular neovascularization trunks at the subBM layer were detected more frequently than distal MNV trunks at the subretinal pigment epithelium layer. Macular neovascularization trunk features at the subBM layer may be related to disease duration and a large choroidal vessel.

CLINICAL IMPLICATION OF RETINAL NERVE FIBER LAYER SCHISIS AND MACULAR FLUORESCEIN LEAKAGE IN PRIMARY IDIOPATHIC EPIRETINAL MEMBRANE.

PURPOSE: We evaluated the relationship between macular fluorescein leakage and retinal nerve fiber layer (RNFL) schisis and investigated the visual prognostic values after pars plana vitrectomy (PPV) and idiopathic epiretinal membrane removal. METHODS: We analyzed the correlations between preoperative optical coherence tomography (OCT) parameters and macular leakage. The final best-corrected visual acuity and central macular thickness were compared according to the presence or absence of macular leakage and RNFL schisis. RESULTS: In 80 eyes with idiopathic epiretinal membrane treated with PPV and membrane peeling, preoperative macular leakage was associated with the presence of preoperative RNFL schisis and inner nuclear layer microcysts. Eyes with both macular leakage and RNFL schisis showed worse postoperative best-corrected visual acuity than those without both factors. CONCLUSION: In the presence of macular fluorescein leakage and RNFL schisis, postoperative best-corrected visual acuity is worse, and improvements in the central macular thickness are greater than those in the absence of both factors.

GANGLION CELL-INNER PLEXIFORM LAYER THICKNESS IN EYES WITH NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION OF DIFFERENT DRUSEN SUBTYPES.

PURPOSE: We sought to investigate the ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with nonexudative age-related macular degeneration. METHODS: We classified eyes into four categories-pachydrusen, soft drusen, subretinal drusenoid deposit (SDD), and soft drusen with SDD-and compared the baseline mean macular GCIPL thickness according to the Early Treatment Diabetic Retinopathy Study grid and its change between groups. RESULTS: We classified 53, 29, 36, and 34 eyes into the four categories, respectively. The mean GCIPL thickness values in the 3-mm area were 82.61 ± 9.54 µm for the pachydrusen group, 79.11 ± 10.26 µm for the soft drusen group, 77.72 ± 6.04 µm for the SDD group, and 71.63 ± 8.69 µm for the soft drusen with SDD group (P < 0.001). The soft drusen with the SDD group showed a greater change in GCIPL thickness (-2.50 ± 0.29 µm/year) in the 3-mm area as compared with the pachydrusen group (-0.18 ± 0.35 µm/year), soft drusen group (-0.55 ± 0.36 µm/year), and SDD group (-0.55 ± 0.37) (all P < 0.001). CONCLUSION: The GCIPL thickness varied according to the type of nonexudative age-related macular degeneration. The thinner baseline GCIPL and its greater change in eyes with soft drusen with SDD may suggest that these eyes are experiencing more prominent neuroretinal degeneration in the central 3-mm area than those in the other groups.

MACULAR HOLE ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION: Pathogenesis and Surgical Outcomes.

PURPOSE: To ascertain the pathogenesis of macular hole (MH) associated with age-related macular degeneration (AMD) and its surgical outcomes. METHODS: Patients with full-thickness MH associated with AMD (higher grades than intermediate) were enrolled. The mechanism of MH formation and closure rate after vitrectomy (surgical outcome) were determined using optical coherence tomography imaging. RESULTS: The mechanism of MH formation (35 eyes) associated with AMD was classified into four types: vitreomacular traction (42.9%), gradual retinal thinning caused by subretinal drusen or pigment epithelial detachment (22.9%), massive subretinal hemorrhage (20.0%), and combined (14.3%). In the 41 eyes that underwent vitrectomy, the logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.82 (0.10-2.30) preoperative to 0.69 (0.10-2.30) postoperative (P = 0.001). Successful closure of the MH was achieved in 33 eyes (80.5%) after vitrectomy. No significant association was observed between the closure rate of MH after vitrectomy and mechanism of MH formation (P = 0.083). CONCLUSION: The mechanism of MH formation associated with AMD was classified into four types and was not related to its surgical outcome. Considering visual improvement and surgical outcome after vitrectomy in our study, active surgical treatment can be considered for MH associated with AMD.

Surface-Deactivated Core-Shell Metal-Organic Framework by Simple Ligand Exchange for Enhanced Size Discrimination in Aerobic Oxidation of Alcohols.

Metal-organic frameworks (MOFs) are an attractive catalyst support for stable immobilization of the active sites in their scaffold due to the high tunability of organic ligands. The active site-functionalized ligands can be easily employed to construct MOFs as porous heterogeneous catalysts. However, the existence of active sites on the external surfaces as well as internal pores of MOFs seriously impedes the selective reaction in the pore. Herein, through a simple post-synthetic ligand exchange (PSE) method we synthesized surface-deactivated (only core-active) core-shell-type MOF catalysts, which contain 2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) groups on the ligand as active sites for aerobic oxidation of alcohols. The porous but catalytically inactive shell ensured the size-selective permeability by sieving effects and induced all reactions to take place in the pores of the catalytically active core. Because PSE is a facile and universal approach, this can be rapidly applied to a variety of MOF-based catalysts for enhancing reaction selectivity.

Positional Installation of Unsymmetrical Fluorine Functionalities onto Metal-Organic Frameworks for Efficient Carbon Dioxide Separation under Humid Conditions.

Unsymmetrical trifluoro functional groups were installed onto metal-organic frameworks (MOFs) at positions regulated by ligand exchange for efficient CO2 separation under humid conditions. These trifluoro groups induced molecular separation via dipole-dipole interactions. Their installation onto amino-functionalized MOF surfaces produced hydrophobic and CO2-philic core-shell MOFs for efficient CO2 adsorption.

Sequential Connection of Mutually Exclusive Catalytic Reactions by a Method Controlling the Presence of an MOF Catalyst: One-Pot Oxidation of Alcohols to Carboxylic Acids.

A functionalized metal-organic framework (MOF) catalyst applied to the sequential one-pot oxidation of alcohols to carboxylic acids controls the presence of a heterogeneous catalyst. The conversion of alcohols to aldehydes was acquired through aerobic oxidation using a well-known amino-oxy radical-functionalized MOF. In the same flask, a simple filtration of the radical MOF with mild heating of the solution completely altered the reaction media, providing radical scavenger-free conditions suitable for the autoxidation of the aldehydes formed in the first step to carboxylic acids. The mutually exclusive radical-catalyzed aerobic oxidation (the first step with MOF) and radical-inhibited autoxidation (the second step without MOF) are sequentially achieved in a one-pot manner. Overall, we demonstrate a powerful and efficient method for the sequential oxidation of alcohols to carboxylic acids by employing a readily functionalizable heterogeneous MOF. In addition, our MOF in-and-out method can be utilized in an environmentally friendly way for the oxidation of alcohols to carboxylic acids of industrial and economic value with broad functional group tolerance, including 2,5-furandicarboxylic acid and 1,4-benzenedicarboxylic acid, with good yield and reusability. Furthermore, MOF-TEMPO, as an antioxidative stabilizer, prevents the undesired oxidation of aldehydes, and the perfect "recoverability" of such a reactive MOF requires a re-evaluation of the advantages of MOFs from heterogeneity in catalytic and related applications.

FEATURES OF THE MACULAR AND PERIPAPILLARY CHOROID AND CHORIOCAPILLARIS IN EYES WITH NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We investigated macular and peripapillary choroidal thickness (CT) and flow voids in the choriocapillaris in eyes with nonexudative age-related macular degeneration. METHODS: We retrospectively reviewed the medical records of patients with nonexudative age-related macular degeneration and classified their eyes into three categories: pachydrusen, drusen, and subretinal drusenoid deposit. Mean macular and peripapillary CT and choriocapillaris flow void area were compared among the three groups. RESULTS: The three groups included 29, 33, and 33 patients, respectively. The mean macular and peripapillary CT findings were 260.64 ± 75.85 µm and 134.47 ± 46.28 µm for the pachydrusen group; 163.63 ± 64.08 µm and 93.47 ± 39.07 µm for the drusen group; and 95.33 ± 28.87 µm and 56.06 ± 11.64 µm for the subretinal drusenoid deposit group (all, P < 0.001). Mean macular and peripapillary flow void area varied among the subretinal drusenoid deposit group (57.07 ± 6.16% and 55.38 ± 6.65%), drusen group (58.30 ± 6.98% and 49.11 ± 9.11%) and pachydrusen group (50.09 ± 5.77% and 45.47 ± 8.06%) (all P < 0.001). CONCLUSION: The peripapillary CT and flow voids in the choriocapillaris varied according to the features of drusen in nonexudative age-related macular degeneration eyes. Greater flow voids and thinner CT in eyes with subretinal drusenoid deposits may suggest that these eyes have diffuse choroidal abnormalities both in and outside the macula.

MORPHOLOGIC FEATURES OF THE RETINAL PIGMENT EPITHELIUM AND ASSOCIATED CHORIORETINAL CHARACTERISTICS IN EYES WITH EARLY AGE-RELATED MACULAR DEGENERATION AND SUBRETINAL DRUSENOID DEPOSITS.

PURPOSE: To investigate the features of the retinal pigment epithelium (RPE) on optical coherence tomography in eyes with early age-related macular degeneration with subretinal drusenoid deposit. METHODS: We classified the eyes into three types: nonundulating RPE, undulating RPE, and wedge-shaped RPE. We compared the retinal vessel densities, retinal thickness, and choroidal thickness of a 3-mm-diameter zone. RESULTS: We classified 33, 27, and 20 as nonundulating RPE, undulating RPE, and wedge-shaped RPE eyes, respectively. The vascular densities of the superficial and deep capillary plexus showed differences; nonundulating RPE group (23.93 ± 2.26% and 23.54 ± 1.78%), undulating RPE group (22.29 ± 2.80% and 21.94 ± 2.42%), and wedge-shaped RPE group (21.93 ± 2.70% and 20.63 ± 2.42%, P = 0.010 and P < 0.001). The mean retinal thickness and choroidal thickness were also different, nonundulating RPE group (298.26 ± 13.81 µm and 180.08 ± 55.49 µm), undulating RPE group (285.29 ± 21.88 µm and 148.45 ± 55.08 µm), and wedge-shaped RPE group (274.86 ± 20.62 µm and 135.75 ± 39.77 µm) (P = 0.001 and P = 0.007). CONCLUSION: Altered features of the RPE on optical coherence tomography may indicate advancement in disease and be part of an overall degeneration process in these eyes.

Choriocapillaris flow features and choroidal vasculature in the fellow eyes of patients with acute central serous chorioretinopathy.

PURPOSE: The purpose of the study is to investigate the characteristics of choriocapillaris flow based on the underlying choroidal vasculature in fellow eyes with central serous chorioretinopathy (CSC). METHODS: We included 57 patients with CSC and normal controls. Characteristics of choriocapillaris flow were evaluated using swept-source optical coherence tomography (OCT) angiography. We divided the choroidal layer into the vascular and stromal beds according to the choroid vessels on en-face OCT images. We compared the flow void area and mean vascular density of the choriocapillaris according to the underlying choroidal beds in the CSC and control group. RESULTS: The mean vascular density of the choriocapillaris in the CSC group was not different from that of the control group (P = 0.289). The flow void area was more frequently found in the CSC group (59.6%) than in the control group (29.8%, P = 0.002). The presence of the flow void area in the CSC group was associated with greater macular choroidal thickness (P = 0.004). In the CSC group, the mean flow void area and ratio of the choriocapillaris over the vascular bed were larger than those over the stromal bed (all P < 0.001). CONCLUSIONS: The location of the flow void area of the choriocapillaris was associated with the distribution of the underlying choroidal vessels. This suggests that the underlying choroidal vessels may affect choriocapillaris perfusion in pachychoroid eyes.

OCULAR PERFUSION PRESSURE AND CHOROIDAL THICKNESS IN CENTRAL SEROUS CHORIORETINOPATHY AND PIGMENT EPITHELIOPATHY.

PURPOSE: To investigate ocular perfusion pressure (OPP) in patients with central serous chorioretinopathy (CSC) and pigment epitheliopathy (PE). METHODS: In this retrospective study, we included patients with acute idiopathic unilateral CSC and age- and sex-matched normal controls. The patients with CSC were classified into two groups according to the PE presence on their fellow eyes. We compared OPP among CSC patients with or without PE and normal controls. RESULTS: Among a total of 47 patients with CSC, 21 were classified into the PE group and 26 into the non-PE group. The mean OPP (±SD) of CSC and fellow eyes in the PE group (50.02 ± 4.98 and 50.83 ± 4.12 mmHg, respectively) was greater than that in the non-PE group (43.69 ± 6.88 and 44.0 ± 6.57 mmHg, respectively) and normal controls (45.64 ± 8.73 mmHg) (all, P < 0.05). The mean macular choroidal thickness of CSC and fellow eyes in the PE group (344.4 ± 31.8 and 310.1 ± 37.0 µm, respectively) was thicker than that in the non-PE group (318.5 ± 43.8 and 282.8 ± 36.1 µm, respectively) (all, P < 0.05). Greater macular choroidal thickness and higher OPP were associated with PE (P = 0.002 and P = 0.003). CONCLUSION: Forty-five percent of the patients with acute unilateral CSC had PE in their fellow eyes. Increased OPP may influence the development of bilateral CSC characteristics.

Fully Integrated Light-Sensing Stimulator Design for Subretinal Implants.

This paper presents a fully integrated photodiode-based low-power and low-mismatch stimulator for a subretinal prosthesis. It is known that a subretinal prosthesis achieves 1600-pixel stimulators on a limited single-chip area that is implanted beneath the bipolar cell layer. However, the high-density pixels cause high power dissipation during stimulation and high fabrication costs because of special process technologies such as the complementary metal-oxide semiconductor CMOS image sensor process. In addition, the many residual charges arising from the high-density pixel stimulation have deleterious effects, such as tissue damage and electrode corrosion, on the retina tissue. In this work, we adopted a switched-capacitor current mirror technique for the single-pixel stimulator (SPStim) that enables low power consumption and low mismatch in the subretinal device. The customized P+/N-well photodiode used to sense the incident light in the SPStim also reduces the fabrication cost. The 64-pixel stimulators are fabricated in a standard 0.35-µm CMOS process along with a global digital controller, which occupies a chip area of 4.3 × 3.2 mm² and are ex-vivo demonstrated using a dissected pig eyeball. According to measured results, the SPStim accomplishes a maximum biphasic pulse amplitude of 143 µA, which dissipates an average power of 167 µW in a stimulation period of 5 ms, and an average mismatch of 1.12 % between the cathodic and anodic pulses.

Defect Engineering into Metal-Organic Frameworks for the Rapid and Sequential Installation of Functionalities.

Postsynthetic treatments are well-known and important functionalization tools of metal-organic frameworks (MOFs). Herein, we have developed a practical and rapid postsynthetic ligand exchange (PSE) strategy using a defect-controlled MOF. An increase in the number of defects amounts to MOFs with enhanced rates of ligand exchange in a shorter time frame. An almost quantitative exchange was achieved by using the most defective MOFs. This PSE strategy is a straightforward method to introduce a functionality into MOFs including bulky or catalytically relevant moieties. Furthermore, some mechanistic insights into PSE were revealed, allowing for a sequential ligand exchange and the development of multifunctional MOFs with controlled ligand ratios.

Choriocapillaris layer imaging with swept-source optical coherence tomography angiography in lamellar and full-thickness macular hole.

PURPOSE: To present characteristics of choriocapillaris layer imaging with swept-source optical coherence tomography angiography (SS-OCTA) in eyes with macular hole (MH). METHODS: Patients with MH were included. Vascular density of choriocapillaris (VDC) and central flow void areas were obtained using SS-OCTA. Data were compared with age- and gender-matched normal controls. RESULTS: Fifty-one patients with MH and 51 controls were included. Among the 51 patients with MH, 19 had lamellar MH (LMH) and 32 had full-thickness MH (FTMH). While VDC in LMH (79.26 ± 4.06%) was not significantly different from that seen in fellow eyes (79.88 ± 4.28%, P = 0.729) and normal controls (80.53 ± 4.21%, P = 1.000), VDC in surgically closed FTMH (74.60 ± 7.37%) was similar to that of fellow eyes (75.45 ± 7.39%, P = 0.400) but lower than that of controls (78.37 ± 7.13%, P = 0.011). On univariate analysis of 32 patients with unilateral sealed FTMH, VDC was not correlated with basal hole area (P = 0.797) or preoperative area of disrupted ellipsoid zone (P = 0.863). Central flow void was detected in 32 eyes. Mean central flow void area was 0.82 ± 0.84 mm2, which correlated with preoperative area of disrupted ellipsoid zone (P = 0.001). CONCLUSIONS: Choriocapillaris layer imaging using SS-OCTA showed that choriocapillaris in both eyes of patients with unilateral FTMH had different characteristics from eyes with LMH or normal controls. These results suggest that variation in choriocapillaris layer flow is involved in the pathogenesis of MH.

Retinal vascular flow and choroidal thickness in eyes with early age-related macular degeneration with reticular pseudodrusen.

BACKGROUND: To investigate the characteristics of retinal vessels and retinal thickness in eyes with early age-related macular degeneration (AMD) with or without reticular pseudodrusen. METHODS: We retrospectively evaluated the clinical history and optical coherence tomography (OCT) and OCT angiography images of consecutive patients with early AMD. We calculated the retinal vessel densities of the superficial and deep capillary plexus with the ImageJ software (National Institutes of Health, Bethesda, MD, USA) and investigated the relationship with mean retinal thickness and subfoveal choroidal thickness. RESULTS: We included 135 early AMD eyes and classified 60 of them into a reticular pseudodrusen group and 75 into a non-reticular pseudodrusen group. The vascular densities of the superficial and deep capillary plexus in the reticular pseudodrusen group (32.35% ± 3.67 and 26.71% ± 2.88%) were not different from those of the non-reticular pseudodrusen group (33.18% ± 2.2% and % 27.43 ± 1.79%; P = 0.546 and P = 0.318, respectively). The retinal thickness of the reticular pseudodrusen group (287.31 µm ± 24.36 µm) did not differ from that of the non-reticular pseudodrusen group (294.27 µm ± 20.71 µm; P = 0.493), while subfoveal choroidal thickness in the reticular pseudodrusen group (158.13 µm ± 42.53 µm) was lower than that in the non-reticular pseudodrusen group (237.89 µm ± 60.94 µm; P <  0.001). Multivariate analysis revealed that lower vascular density of the superficial capillary plexus and subfoveal choroidal thickness were associated with retinal thinning in reticular pseudodrusen group (P = 0.003 and P = 0.036) and older age was associated with retinal thickness in the non-reticular pseudodrusen group (P = 0.005). CONCLUSIONS: Retinal thinning in early AMD patients with reticular pseudodrusen was accompanied by choroidal and retinal vascular loss, which suggests a possible linkage of retinal thinning with vascular alterations.

Signaling Pathway for Endothelin-1- and Phenylephrine-Induced cAMP Response Element Binding Protein Activation in Rat Ventricular Myocytes: Role of Inositol 1,4,5-Trisphosphate Receptors and CaMKII.

BACKGROUND/AIMS: Endothelin-1 (ET-1) and the α₁-adrenoceptor agonist phenylephrine (PE) activate cAMP response element binding protein (CREB), a transcription factor implicated in cardiac hypertrophy. The signaling pathway involved in CREB activation by these hypertrophic stimuli is poorly understood. We examined signaling pathways for ET-1- or PE-induced cardiac CREB activation. METHODS: Western blotting was performed with pharmacological and genetic interventions in rat ventricular myocytes. RESULTS: ET-1 and PE increased CREB phosphorylation, which was inhibited by blockade of phospholipase C, the extracellular-signal-regulated kinase 1/2 (ERK1/2) pathway, protein kinase C (PKC) or Ca2+-calmodulin-dependent protein kinase II (CaMKII). Intracellular Ca2+ buffering decreased ET-1- and PE-induced CREB phosphorylation by ≥80%. Sarcoplasmic reticulum Ca2+ pump inhibitor, inositol 1,4,5-trisphosphate receptor (IP₃R) blockers, or type 2 IP₃R (IP₃R2) knock-out abolished ET-1- or PE-induced CREB phosphorylation. ET-1 and PE increased phosphorylation of CaMKII and ERK1/2, which was eliminated by IP₃R blockade/knock-out or PKC inhibition. Activation of CaMKII, but not ERK1/2, by these agonists was sensitive to Ca2+ buffering or to Gö6976, the inhibitor of Ca2+-dependent PKC and protein kinase D (PKD). CONCLUSION: CREB phosphorylation by ET-1 and PE may be mainly mediated by IP₃R2/Ca2+-PKC-PKD-CaMKII signaling with a minor contribution by ERK1/2, linked to IP₃R2 and Ca2+-independent PKC, in ventricular myocytes.