Cold-induced suspension and resetting of Ca2+ and transcriptional rhythms in the suprachiasmatic nucleus neurons.

Does the circadian clock keep running under such hypothermic states as daily torpor and hibernation? This fundamental question has been a research subject for decades but has remained unsettled. We addressed this subject by monitoring the circadian rhythm of clock gene transcription and intracellular Ca2+ in the neurons of the suprachiasmatic nucleus (SCN), master circadian clock, in vitro under a cold environment. We discovered that the transcriptional and Ca2+ rhythms are maintained at 22°C-28°C, but suspended at 15°C, accompanied by a large Ca2+ increase. Rewarming instantly resets the Ca2+ rhythms, while transcriptional rhythms reach a stable phase after the transient state and recover their phase relationship with the Ca2+ rhythm. We conclude that SCN neurons remain functional under moderate hypothermia but stop ticking in deep hypothermia and that the rhythms reset after rewarming. These data also indicate that stable Ca2+ oscillation precedes clock gene transcriptional rhythms in SCN neurons.

The circadian clock in the piriform cortex intrinsically tunes daily changes of odor-evoked neural activity.

The daily activity in the brain is typically fine-tuned by the circadian clock in the local neurons as well as by the master circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. In the olfactory response, odor-evoked activity in the piriform cortex (PC) and olfactory behavior retain circadian rhythmicity in the absence of the SCN, yet how the circadian rhythm in the PC is achieved independently of the SCN remains elusive. Here, to define neurons regulating the circadian rhythm of the odor-evoked activity in the PC, we knocked out the clock gene Bmal1 in a host of specific neurons along the olfactory circuit. We discovered that Bmal1 knockout in the PC largely abolishes the circadian rhythm of the odor-evoked activity. We further showed that isolated PC exhibits sustained circadian rhythms of the clock gene Per2 expression. Quantitative PCR analysis revealed that expression patterns of multiple genes involved in neural activity and synaptic transmission exhibit circadian rhythm in the PC in a BMAL1-dependent manner. Our findings indicate that BMAL1 acts intrinsically in the PC to control the circadian rhythm of the odor-evoked activity in the PC, possibly through regulating expression patterns of multiple genes involved in neural activity and transmission.

Diurnal variation in declarative memory and the involvement of SCOP in cognitive functions in nonhuman primates.

Cognitive functions depend on the time of day in various organisms. Previously, we found that 24-h recognition memory performance of nocturnal mice changes diurnally through SCOP protein-dependent regulation. It remains unknown whether diurnal change and SCOP-dependent regulation of memory performance are conserved across species with diurnal/nocturnal habits. We tested whether the memory performance of diurnal Japanese macaques depends on the time of day. The memory association between bitter taste of drinking water and the nozzle color of the water bottle was established during the light period of the day to evaluate of memory performance for macaques. Here we found diurnal variation of declarative memory in Japanese macaques. The middle of the daytime is the most effective time for memory performance during the light period. To assess whether SCOP is involved in declarative memory performance, we interfered with SCOP expression by using lentiviral vector expressing shRNA against Scop in the hippocampus of Japanese macaques. Scop knockdown in the hippocampus abrogated the memory performance in the middle of the daytime. Our results implicate that SCOP in the hippocampus is necessary for the diurnal rhythm of the memory system and that the SCOP-dependent memory regulation system may be conserved in mammals.

Comparison of 12-month surgical outcomes of ab interno trabeculotomy with phacoemulsification between spatula-shaped and dual-blade microhooks.

PURPOSE: To compare 12-month clinical results of spatula-shaped and dual-blade microhooks ab interno trabeculotomy with phacoemulsification. STUDY DESIGN: Retrospective comparative study. METHODS: We conducted a retrospective chart review of Japanese open-angle glaucoma patients who underwent ab interno trabeculotomy with phacoemulsification with a 12-month follow-up. Two types of trabecular hook were used: the spatula-shaped Tanito Trabeculotomy ab interno Micro-hook® and the Kahook Dual Blade®. Changes in intraocular pressure (IOP) and medication scores comprised the main outcome metrics. We also analyzed and compared patient demographics and the occurrence of complications. RESULTS: Trabeculotomy was performed using a spatula-shaped hook in 17 eyes and a dual-blade hook in 15 eyes. Significant reductions in IOP (p < 0.001) and medication scores (p < 0.001) were noted in both groups after the 1-month time point. The percentage changes of IOP from baseline at each time point were not significantly different between groups, though there was a significant difference in medication scores at 12 months (p = 0.0192). Postoperative complications occurred similarly in both groups; one case in the dual-blade group required additional filtration surgery. CONCLUSIONS: Ab interno trabeculotomy with phacoemulsification was effective in lowering IOP both with spatula-shaped and with double-blade microhooks. At 12 months more medications were used postoperatively in the spatula-shaped microhook group; however, the reductions in the medication scores from baseline were statistically significant in both groups.

Twelve-month surgical outcome and prognostic factors of stand-alone ab interno trabeculotomy in Japanese patients with open-angle glaucoma.

The purpose of the study was to evaluate the 12-month surgical outcome and prognostic factors of stand-alone ab interno trabeculotomy. The changes in the intraocular pressure (IOP) and medication score and the success rate of the surgery were analyzed. Thirty-four eyes of 29 patients with primary open-angle glaucoma (POAG; n = 16) or pseudoexfoliation glaucoma (PEG; n = 18) with a 12-month follow-up period were included in the study. The decreases in IOP and medication score from the baseline to the all-time-point were statistically significant (P < 0.001). The surgical success rates were 97.1%, 76.5%, and 44.0% at 3 months (90 days), 6 months (180 days), and 12 months (365 days), respectively. A mixed effect Cox model revealed that the type of glaucoma (POAG) was significantly associated with surgical failure (P = 0.044). Furthermore, the surgical success rate was significantly higher in eyes with PEG than it was in those with POAG (P = 0.019). Stand-alone ab interno trabeculotomy significantly lowered both the IOP and the medication score in patients with glaucoma, although almost one quarter of the cases needed additional glaucoma surgeries. The surgical success rate was significantly higher in eyes with PEG than it was in those with POAG.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY STUDY OF CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH EARLY-ONSET DRUSEN.

PURPOSE: To report three middle-aged cases with choroidal neovascularization (CNV) associated with early-onset drusen documented with optical coherence tomography angiography (OCTA). METHODS: Three patients with bilateral early-onset drusen were referred to our hospital. Fundus examination, fluorescein angiography, indocyanine green angiography, OCTA, and other multimodal imaging were performed. RESULTS: Case 1 involved a 47-year-old woman who presented with sudden unilateral anorthopia. She had no previous systemic pathologies. Funduscopic examination and fluorescein angiography revealed bilateral large colloid drusen accompanied by unilateral mild subretinal hemorrhage. Indocyanine green angiography revealed CNV, although it was unclear in fluorescein angiography. Optical coherence tomography angiography also showed interconnecting CNV beneath the retinal pigment epithelium. Case 2 involved a 40-year-old woman with membranoproliferative glomerulonephritis Type 3 who presented with unilateral anorthopia. On fluorescein angiography, cuticular drusen secondary to membranoproliferative glomerulonephritis were seen in both eyes. An interconnecting vascular network was revealed with OCTA and indocyanine green angiography indicating Type 1 CNV in the affected eye. Case 3 involved a 47-year-old man without any medical or family history. Predominant large colloid drusen associated with cuticular drusen were seen in both eyes. Unilateral mild serosanguinous changes were accompanied in the macula, where Type 1 CNV was detected with OCTA. CONCLUSION: All our cases with early-onset drusen showed Type 1 CNV that was detected by indocyanine green angiography or OCTA. Optical coherence tomography angiography has a potential to help noninvasively diagnose CNV in the cases of EOD.

Wipi3 is essential for alternative autophagy and its loss causes neurodegeneration.

Alternative autophagy is an Atg5/Atg7-independent type of autophagy that contributes to various physiological events. We here identify Wipi3 as a molecule essential for alternative autophagy, but which plays minor roles in canonical autophagy. Wipi3 binds to Golgi membranes and is required for the generation of isolation membranes. We establish neuron-specific Wipi3-deficient mice, which show behavioral defects, mainly as a result of cerebellar neuronal loss. The accumulation of iron and ceruloplasmin is also found in the neuronal cells. These abnormalities are suppressed by the expression of Dram1, which is another crucial molecule for alternative autophagy. Although Atg7-deficient mice show similar phenotypes to Wipi3-deficient mice, electron microscopic analysis shows that they have completely different subcellular morphologies, including the morphology of organelles. Furthermore, most Atg7/Wipi3 double-deficient mice are embryonic lethal, indicating that Wipi3 functions to maintain neuronal cells via mechanisms different from those of canonical autophagy.

Hippocampal 7α-Hydroxylated Neurosteroids Are Raised by Training and Bolster Remote Spatial Memory with Increase of the Spine Densities.

Neuroactive steroids, termed neurosteroids, are synthesized locally in the brain and influence biological functions including cognition and behavior. These neurosteroids are synthesized from cholesterol by a series of cytochrome P450 enzymes, among which a member of P450 hydroxylase, cytochrome P450-7b1 (CYP7B1), catalyzes the formation of 7α-hydroxylated neurosteroids, 7α-hydroxypregnenolone (7α-OH-Preg) and 7α-hydroxydehydroepiandrosterone (7α-OH-DHEA). Here we demonstrated the occurrence of these neurosteroids in the mouse hippocampus after spatial-learning tasks. Cyp7b1 deficiency impaired remote spatial memory with recent memory mostly unaffected. The hippocampal dendritic spine densities were reduced in Cyp7b1-deficient mice, and they were no more increased by the training. Furthermore, chronic intracerebroventricular administration of a mixture of 7α-OH-Preg and 7α-OH-DHEA rescued the deteriorated remote memory performance in Cyp7b1-deficient mice. It is concluded that the 7α-hydroxylated neurosteroids are required for long-term maintenance of spatial memory, and we suggest that these neurosteroids may induce synaptic remodeling to maintain the hippocampal function.

Comparison of the short-term effectiveness and safety profile of ab interno combined trabeculotomy using 2 types of trabecular hooks.

PURPOSE: To compare the short-term surgical effectiveness and safety profile of ab interno trabeculotomy using 2 types of trabecular hooks. STUDY DESIGN: Retrospective comparative study. PATIENTS AND METHODS: A retrospective chart review was performed on Japanese open-angle glaucoma patients who underwent ab interno trabeculotomy with phacoemulsification and who had a 6-month follow-up. Trabeculotomy was performed using 2 kinds of trabecular hooks, the Tanito ab interno Trabeculotomy Micro-hook (TMH) or the Kahook Dual Blade (KDB). The patients' demographics, preoperative and postoperative intraocular pressures (IOPs), medication scores, and occurrence of complications were analyzed and compared. RESULTS: Fifty-nine eyes with open-angle glaucoma were included in the final analysis. Trabeculotomy was performed using the TMH in 30 eyes (50.8%) and the KDB in 29 eyes (49.2%). Significant decreases in IOP from the baseline (P < 0.001, except for the 1-month time-point in the KDB group, when P < 0.01) after the 1-month time-point and the medication scores (P < 0.001) at all time-points were noted in both groups. However, the percentage changes in the IOP and medication scores from the baseline at each time-point did not differ significantly between the 2 groups, with the exception of the medication score at the 1-month time-point (P < 0.0283). The occurrence of postoperative complications was similar in the 2 groups. CONCLUSIONS: The present study demonstrates the absence of significant differences in IOP and medication score reductions at almost all time-points between the TMH and KDB groups.

Bleb Plication for a Leaking Bleb After Trabeculectomy.

PURPOSE: The purpose of this work was to report a new method for the repair of ischemic bleb leaks. Bleb leakage is a serious complication of glaucoma filtering surgery with mitomycin C. Many surgical methods have been proposed to seal the leakage from a bleb; however, this novel plication method is effective, relatively easy to perform, and safe. METHODS: We describe the case reports of 2 patients with leakage from a bleb who were treated with the new method. The conjunctiva was lifted away from the sclera as extensively as possible around the ischemic conjunctiva toward the fornix using a bleb knife. Thereafter, 10-0 nylon sutures were applied between the nonischemic conjunctiva located just outside the ischemic conjunctiva and the corneal limbus. The ischemic conjunctiva was not removed, but covered with the nonischemic conjunctiva that was advanced toward the corneal limbus by these sutures. RESULTS: After treatment, no recurrence of bleb leakage was observed. Moreover, no ischemic changes were observed in the advanced nonischemic conjunctiva or plicated conjunctiva. CONCLUSION: This new method of bleb plication was effective for sealing bleb leakage.

The usefulness of the retinal sensitivity measurement with a microperimetry for predicting the visual prognosis of branch retinal vein occlusion with macular edema.

PURPOSE: To evaluate the usefulness of the retinal sensitivity in branch retinal vein occlusion (BVO) with macular edema (ME) following the anti-vascular endothelial growth factor (anti-VEGF) treatment. METHODS: Best-corrected visual acuity (BCVA), microperimetry, and optical coherence tomography (OCT) measurements were carried out in 20 patients with BVO with ME, at baseline and 1 month after the anti-VEGF treatment. The relationships among BCVA, mean retinal sensitivity (MS), macular volume (MV), central retinal thickness (CRT), integrity of ellipsoid zone (EZ), mean retinal sensitivity in the most affected quadrant (qMS), and macular volume in the most affected quadrant (qMV) were investigated. In addition, the relationships among the change in BCVA at 1 month (ΔBCVA1m), mean sensitivity in the most affected quadrant at 1 month (ΔqMS1m), MV in the most affected quadrant at 1 month (ΔqMV1m), and CRT at 1 month (ΔCRT1m) were analyzed. The optimal model for BCVA at 3 months after the treatment (BCVA3m) was identified. RESULTS: There was not a significant difference in BCVA (paired Wilcoxon test, p = 0.058) between at baseline and after the treatment, but there were significant differences in MS, MV, CRT, qMS, and qMV (p < 0.05). There was a significant relationship between ΔqMS1m and ΔMV1m, ΔCRT1m, and ΔqMV1m, respectively. ΔMS1m or ΔqMS1m and BCVA at baseline and ΔBCVA1m were selected as explanatory variables in the optimal model for BCVA3m. CONCLUSION: Retinal sensitivity was related to retinal structure, whereas this was not the case with BCVA. In addition, retinal sensitivity was useful to predict BCVA after anti-VEGF therapy.

Lithium ion adduction enables UPLC-MS/MS-based analysis of multi-class 3-hydroxyl group-containing keto-steroids.

Steroids that contain a 3-hydroxyl group (3-OH steroids) are widely distributed in nature. During analysis with ESI-MS, they easily become dehydrated while in the protonated form, resulting in the production of several precursor ions and leading to low sensitivity of detection. To address this analytical challenge, here, we developed a method for the quantitation of 3-OH steroids by LC-MS/MS coupled with post-column addition of lithium (Li) ions to the mobile phase. The Li ion has a high affinity for the keto group of steroids, stabilizing their structures during ionization and permitting detection of analytes exclusively as the lithiated form. This not only improved the intensities of the precursor ions, but also promoted the formation of typical lithiated fragment ions. This improvement made the quantitation by multiple reaction monitoring more sensitive and reliable, as evidenced by 1.53-188 times enhanced detection sensitivity of 13 steroids that contained at least one keto and two hydroxyl groups or one keto and one 5-olefinic double bond, among 16 different 3-OH steroids. We deployed our newly developed method for profiling steroids in mouse brain tissue and identified six steroids in one tissue sample. Among these, 16-hydroxyestrone, tetrahydrocorticosterone, and 17α-hydroxypregnenolone were detected for the first time in the mouse brain. In summary, the method described here enables the detection of lithiated steroids by LC-MS/MS, including three 3-OH steroids not previously reported in the mouse brain. We anticipate that this new method may allow the determination of 3-OH steroids in different brain regions.

Comprehensive analysis of a novel mouse model of the 22q11.2 deletion syndrome: a model with the most common 3.0-Mb deletion at the human 22q11.2 locus.

The 22q11.2 deletion syndrome (22q11.2DS) is associated with an increased risk for psychiatric disorders. Although most of the 22q11.2DS patients have a 3.0-Mb deletion, existing mouse models only mimic a minor mutation of 22q11.2DS, a 1.5-Mb deletion. The role of the genes existing outside the 1.5-Mb deletion in psychiatric symptoms of 22q11.2DS is unclear. In this study, we generated a mouse model that reproduced the 3.0-Mb deletion of the 22q11.2DS (Del(3.0 Mb)/ +) using the CRISPR/Cas9 system. Ethological and physiological phenotypes of adult male mutants were comprehensively evaluated by visual-evoked potentials, circadian behavioral rhythm, and a series of behavioral tests, such as measurement of locomotor activity, prepulse inhibition, fear-conditioning memory, and visual discrimination learning. As a result, Del(3.0 Mb)/ + mice showed reduction of auditory prepulse inhibition and attenuated cue-dependent fear memory, which is consistent with the phenotypes of existing 22q11.2DS models. In addition, Del(3.0 Mb)/ + mice displayed an impaired early visual processing that is commonly seen in patients with schizophrenia. Meanwhile, unlike the existing models, Del(3.0 Mb)/ + mice exhibited hypoactivity over several behavioral tests, possibly reflecting the fatigability of 22q11.2DS patients. Lastly, Del(3.0 Mb)/ + mice displayed a faster adaptation to experimental jet lag as compared with wild-type mice. Our results support the validity of Del(3.0 Mb)/ + mice as a schizophrenia animal model and suggest that our mouse model is a useful resource to understand pathogenic mechanisms of schizophrenia and other psychiatric disorders associated with 22q11.2DS.

Early changes of vascular lesions and responses to combined photodynamic therapy in patients with polypoidal choroidal vasculopathy.

PURPOSE: To evaluate early changes of vascular lesions and their associations with the early responses to combined photodynamic therapy (PDT) in eyes with polypoidal choroidal vasculopathy (PCV). METHODS: This study evaluated 19 eyes of 19 patients with PCV who underwent PDT combined with anti-vascular endothelial growth factor injections and were followed for 3 months. All subjects were examined 1 week and 1, 2, and 3 months after combined PDT. "Active" cases were defined as recurrence or persistence of serous retinal detachment or subretinal hemorrhage detected within 3 months. Branching vascular networks (BVNs) were evaluated by optical coherence tomography angiography (OCTA) and polyps by indocyanine-green angiography. RESULTS: In total, 16%, 58%, 84%, and 89% of eyes displayed BVNs 1 week, 1, 2, and 3 months after PDT, respectively. BVNs were detected significantly more often 1 month after PDT in the "active" group than "inactive" group (89% vs. 30%, p = 0.020). There were significantly higher overall proportions of BVNs detected by OCTA in the "active" group than "inactive" group (p = 0.0058). CONCLUSION: In most cases, BVNs disappeared once and gradually appeared again within 3 months. Detecting BVNs using OCTA from early phases could be a helpful biomarker to assess the early responses to PDT in eyes with PCV.

Correction to: The Japanese version of the questionnaire about the process of recovery: development and validity and reliability testing.

After publication of our article [1] we were notified that the 5-point Likert-type scale in Additional file 1 needs to change from "1 to 5" to "0 to 4". The updated Additional file 1 is included in this correction.

Association between visual function and the integrity of residual ellipsoid zone in resolved central serous chorioretinopathy.

Central serous chorioretinopathy (CSC) usually resolves spontaneously; however, in some patients, it can be chronic and visual impairment remains even after resolution of the serous retinal detachment. The impaired photoreceptor cells often present with disrupted ellipsoid zone (EZ) on optical coherence tomography (OCT). In this study, the integrity of EZ was quantified by calculating the index of residual EZ, identified on binarized OCT images from 25 eyes of 23 patients with resolved CSC. To estimate residual EZ, integrity of residual EZ with the central horizontal line on the fovea (rEZc) and average integrity of residual EZ within 3 × 3-mm macular area (rEZave) were investigated. The interrater reliability of the method was assessed using the intraclass correlation coefficient (ICC). The relationship between LogMAR VA and age, central retinal thickness, central choroidal thickness, rEZc, and rEZave were evaluated using the linear mixed model. Retinal sensitivity was measured with the MP-3 microperimeter and similar analyses were iterated for mean retinal sensitivity (MS). ICC values were 0.938 with rEZc and 0.979 with rEZave. rEZc was significantly related to LogMAR VA (p = 0.039). rEZave was significantly related to MS (p < 0.001). These results suggested potential usefulness of residual EZ to predict visual function in resolved CSC.

The association of choroidal structure and its response to anti-VEGF treatment with the short-time outcome in pachychoroid neovasculopathy.

Pachychoroid neovasculopathy (PNV) shares some anatomical features with other pachychoroid spectrum diseases, but little is known about the characteristics on the treatment with anti-vascular endothelial growth factor (VEGF). We investigated the effect of choroidal structure and responses to anti-VEGF on the prognosis of pachychoroid neovasculopathy (PNV) and other types of neovascular age-related macular degeneration (non-PNV). Twenty-one eyes with PNV and 34 eyes with non-PNV who had anti-VEGF treatment were retrospectively reviewed. Choroidal neovascularization (CNV) area at baseline was measured with fluorescein angiography (FAG). The luminal and stromal area in the choroid was measured by enhanced-depth-imaging (EDI) OCT at baseline and 1 month. The association between dry macula or LogMAR VA (visual acuity, VA) at 1 month and baseline values or changes in the luminal or stromal area at 1 month, baseline CNV area, or anti-VEGF drugs were analyzed in patients with or without PNV. In non-PNV, change of luminal area (coefficient = 7.0×10-5, p = 0.0001), baseline CNV area (coefficient = 0.18, p = 0.033), and aflibercept vs. ranibizumab (coefficient = 0.29, p = 0.0048) were chosen as predictors for dry macula by the model selection. Similarly, in non-PNV, change of luminal area (coefficient = 6.1×10-6, p = 0.033), baseline CNV area (coefficient = 0.034, p = 0.022), and aflibercept vs. ranibizumab (coefficient = 0.056, p = 0.0020) were chosen as predictors for greater VA improvement. In PNV, however, none of these factors was chosen as predictors for dry macula or VA improvement by the model selection. The result of the present study implied that structural response after anti-VEGF might be different between non-PNV and PNV in the treatment with anti-VEGF agents.

Two-year outcome of treat-and-extend aflibercept after ranibizumab in age-related macular degeneration and polypoidal choroidal vasculopathy patients.

BACKGROUND: The purpose of the study was to evaluate the 2-year outcome and predictive factors of treat-and-extend aflibercept in patients with eyes affected by typical neovascular age-related macula degenelation (t-AMD) or polypoidal choroidal vasculopathy (PCV), who were switched from ranibizumab. PATIENTS AND METHODS: The patients underwent three monthly aflibercept injections and subsequent administration following the treat-and-extend protocol. Sixty-two eyes of 62 patients were reviewed retrospectively. R statistical software was used for statistical analysis. RESULTS: Twenty-two eyes were t-AMD and the remaining 40 eyes were PCV. There was no significant difference in the logarithm of the minimal angle of resolution visual acuity (VA) between baseline and 2 years after switching to aflibercept (0.40 vs 0.40; P=0.99). Multivariate analyses suggested that the following factors were significantly correlated with better VA at 2 years after switching to aflibercept: patients with PCV, the absence of intraretinal fluid at baseline, and better VA at baseline. CONCLUSION: In conclusion, VA was maintained and there was an anatomical improvement at 2 years in patients with t-AMD and PCV who were switched from ranibizumab to treat-and-extend aflibercept. PCV patients showed more favorable visual outcomes and less injections at 2 years compared to t-AMD patients. Intraretinal fluid and VA at baseline were predictors of VA at 2 years.

Corneal biomechanical properties are associated with the activity and prognosis of Angioid Streaks.

The aim of the current study is to investigate corneal biomechanical properties in detail using Ocular Response Analyzer (ORA) and Corvis ST (CST) tonometry and to analyze the association between corneal biomechanical properties and the frequency of intravitreal anti-vascular endothelial growth factor (VEGF) injections (FIV) in AS eyes with choroidal neovascularization (CNV). Twenty-eight eyes of 15 patients with AS were enrolled. Mean age of AS patients was 67.9 ± 9.8 years. ORA and CST measurements were carried out, in addition to comprehensive ophthalmic examinations. LogMAR visual acuity (VA) and ΔVA (the change of VA from baseline to the final visit) were calculated in each eye. Also, the relationships between FIV, and the variables of initial age at the observation period, axial length, and corneal biomechanical properties were investigated in eyes with AS using linear mixed model with model selection using AICc. In 28 AS eyes, 16 eyes underwent intravitreal anti-VEGF injections during follow-up period. Lower corneal hysteresis (CH), higher corneal resistant factor (CRF) and higher CST measured the DA ratio were associated with the increase of FIV in AS eyes (p = 0.01, p = 0.002, p = 0.027, respectively), suggesting the usefulness for monitoring of corneal biomechanical properties.

Choroidal structure as a biomarker for visual acuity in intravitreal aflibercept therapy for polypoidal choroidal vasculopathy.

PURPOSE: To investigate the relationship between choroidal structure and visual acuity after intravitreal aflibercept therapy for polypoidal choroidal vasculopathy (PCV). METHODS: We conducted a retrospective, single-centre and observational study including 18 eyes of 18 patients with PCV (73.8 ± 10.2 years of age) who were treated with three monthly intravitreal aflibercept injections followed by additional treatments in a treat-and-extend protocol. The cross-sectional images of the macula were obtained with enhanced depth imaging optical coherence tomography at baseline, at 3 months, and at 12 months. The choroidal layer was divided into luminal or stromal segments by applying binarization processing to calculate these areas. The relationships between age, spherical equivalent, best-corrected visual acuity (BCVA), baseline value, or changes in the luminal or the stromal areas, and the BCVA change at 12 months were analysed using multiple regression analyses and model selection procedures. RESULTS: Both stromal and luminal areas were decreased at 3 and 12 months compared to baseline areas (5% and 9% at 3 months, 6% and 12% at 12 months, p < 0.0001, p < 0.0001, p < 0.0001 and p < 0.0001, respectively). Greater improvement of visual acuity (VA) at 12 months was significantly associated with younger age, greater spherical equivalent, worse baseline BCVA, greater baseline luminal area, and smaller baseline stromal area. CONCLUSIONS: Choroidal structure might be useful as a new biomarker for potential Visual outcomes after intravitreal aflibercept therapy for PCV.