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The visibility of anterior hyaloid membrane (AHM) and Berger’s space in phakic eyes was investigated. In 624 eyes of 624 patients, the retrolental space was scanned with the deep-range anterior segment optical coherence tomography (AS-OCT, CASIA2, Tomey). Subgroup analysis was conducted in 223 eyes undergoing cataract surgery. The logistic regression analysis using the backward-elimination method was performed to evaluate the influence of various factors on the visibility of AHM (dependent variable). Explanatory variables included age, gender, axial length, corneal power, corneal cylinder, and the Co III gradings. Intrarater repeatability for AHM visibility was excellent with the prevalence-adjusted bias-adjusted kappa (κ coefficient) of 0.90. AHM was observed in 43 eyes (6.9%). The patients with visible AHM (68.1 ± 8.8 years) were significantly older than those without visible AHM (52.6 ± 25.6 years) (p < 0.001). The logistic regression analysis in the cataract surgery subgroup revealed that axial length (p = 0.030) and corneal power (p = 0.043) were significantly associated with AHM visibility. The mean absolute refractive error from target was significantly larger in eyes with visible AHM (0.670 ± 0.384 D) than with invisible AHM (0.494 ± 0.412 D) (p = 0.037). The postoperative refractive prediction was less accurate in eyes with visible AHM, but no significant tendency existed in terms of myopic or hyperopic shifts.

PurposeSubretinal injection (SRI) in mice is widely used in retinal research, yet the learning curve (LC) of this surgically challenging technique is unknown.MethodsTo evaluate the LC for SRI in a murine model, we analyzed training data from 3 clinically trained ophthalmic surgeons from 2018 to 2020. Successful SRI was defined as either the absence of retinal pigment epithelium (RPE) degeneration after phosphate buffer saline injection and the presence of RPE degeneration afterAluRNA injection. Multivariable survival-time regression models were used to evaluate the association between surgeon experience and success rate, with adjustment for injection agents, and to calculate an approximate case number to achieve a 95% success rate. A Cumulative Sum (CUSUM) analysis was performed and plotted individually to monitor each surgeon’s simultaneous performance.ResultsDespite prior microsurgery experience, the combined average success rate of the first 50 cases in mice was only 27%. The predicted SRI success rate did not reach a plateau above 95% until approximately 364 prior cases. Using the 364-training case as a “cutoff” point, the predicted probability of success before and after the 364thcase was 65.38% and 99.32%, respectively (P< 0.0001). CUSUM analysis showed an initial upward slope and then remained within the decision intervals with an acceptable success rate set at 95% in the late stage.ConclusionsThis study demonstrates the complexity and substantial LC for successful SRI in mice with high confidence. A systematic training system could improve the reliability and reproducibility of SRI-related experiments and improve the interpretation of experimental results using this technique.Translational RelevanceOur prediction model and monitor system allow objective quantification of technical proficiency in the field of subretinal drug delivery and gene therapy for the first time.

Description, Endogenous Alu cDNA triggers inflammasome-mediated cell death in age-related macular degeneration., Long interspersed nuclear element-1 (L1)–mediated reverse transcription (RT) of Alu RNA into cytoplasmic Alu complementary DNA (cDNA) has been implicated in retinal pigmented epithelium (RPE) degeneration. The mechanism of Alu cDNA–induced cytotoxicity and its relevance to human disease are unknown. Here we report that Alu cDNA is highly enriched in the RPE of human eyes with geographic atrophy, an untreatable form of age-related macular degeneration. We demonstrate that the DNA sensor cGAS engages Alu cDNA to induce cytosolic mitochondrial DNA escape, which amplifies cGAS activation, triggering RPE degeneration via the inflammasome. The L1-extinct rice rat was resistant to Alu RNA–induced Alu cDNA synthesis and RPE degeneration, which were enabled upon L1-RT overexpression. Nucleoside RT inhibitors (NRTIs), which inhibit both L1-RT and inflammasome activity, and NRTI derivatives (Kamuvudines) that inhibit inflammasome, but not RT, both block Alu cDNA toxicity, identifying inflammasome activation as the terminal effector of RPE degeneration.

This study was performed to compare anterior ocular biometric measurements of deep-range swept-source anterior segment optical coherence tomography (AS-OCT) (CASIA2) versus short-range swept-source AS-OCT (CASIA SS-1000), ultrasonography (AL-4000), and Scheimpflug camera analysis (Pentacam and EAS-1000) in patients with cataract. One hundred eighty-five eyes of 128 participants with mild refractive error or cataract were examined. The central corneal thickness (CCT), aqueous depth (AQD), and lens thickness were obtained. The repeatability of CASIA2 measurements was assessed. In patients with cataract, the CCT, AQD, lens thickness, and lens anterior curvature by CASIA2 showed high intraclass correlation coefficients (ICCs) of > 0.99. Conversely, measurements of the posterior part of the lens such as lens posterior curvature showed lower ICCs. The ICCs were higher in healthy young participants than in patients with cataract. The ICCs tended to be lower in patients with mild than dense cataract. There was no statistically significant difference in the CCT and AQD between the CASIA2 and CASIA SS-1000 or in the lens thickness measurements between the CASIA2 and AL-4000 and between the CASIA2 and EAS-1000. There was a significant linear correlation in the biometric measurements between the CASIA2 and the other instruments. We evaluated the biometric measurements of the anterior eye segment by the CASIA2. The CASIA2 yielded results comparable with those of the CASIA SS-1000, ultrasonography, and Scheimpflug camera. However, mild cataract decreased the repeatability of measurements of the posterior part of the lens.

Subretinal injection (SRI) is a widely used technique in retinal research and can be used to deliver nucleic acids, small molecules, macromolecules, viruses, cells or biomaterials such as nanobeads. Here we describe how to undertake SRI of mice. This protocol was adapted from a technique initially described for larger animals. Although SRI is a common procedure in eye research laboratories, there is no published guidance on the best practices for determining what constitutes a 'successful' SRI. Optimal injections are required for reproducibility of the procedure and, when carried out suboptimally, can lead to erroneous conclusions. To address this issue, we propose a standardized protocol for SRI with 'procedure success' defined by follow-up examination of the retina and the retinal pigmented epithelium rather than solely via intraoperative endpoints. This protocol takes 7-14 d to complete, depending on the reagent delivered. We have found, by instituting a standardized training program, that trained ophthalmologists achieve reliable proficiency in this technique after ~350 practice injections. This technique can be used to gain insights into retinal physiology and disease pathogenesis and to test the efficacy of experimental compounds in the retina or retinal pigmented epithelium.

In this paper, we demonstrate polarization-sensitive optical coherence tomography (PS-OCT) based tissue dynamics imaging methods to investigate the activity of mouse livers. The methods include logarithmic intensity variance (LIV), temporal variance of birefringence, temporal degree-of-polarization-uniformity. Portal veins appeared as hypo-scattering structure in static OCT intensity. High dynamics appearance around the portal veins in all the dynamics contrasts was found just after the dissection of mouse liver. Although, high activity around the vessels reduced by time, a bright and high dynamics spot appeared in the vessel in LIV cross-sectional and en face image after 28-hours of the dissection.

Alu retroelements propagate via retrotransposition by hijacking long interspersed nuclear element-1 (L1) reverse transcriptase (RT) and endonuclease activities. Reverse transcription of Alu RNA into complementary DNA (cDNA) is presumed to occur exclusively in the nucleus at the genomic integration site. Whether Alu cDNA is synthesized independently of genomic integration is unknown. Alu RNA promotes retinal pigmented epithelium (RPE) death in geographic atrophy, an untreatable type of age-related macular degeneration. We report that Alu RNA-induced RPE degeneration is mediated via cytoplasmic L1–reverse-transcribed Alu cDNA independently of retrotransposition. Alu RNA did not induce cDNA production or RPE degeneration in L1-inhibited animals or human cells. Alu reverse transcription can be initiated in the cytoplasm via self-priming of Alu RNA. In four health insurance databases, use of nucleoside RT inhibitors was associated with reduced risk of developing atrophic macular degeneration (pooled adjusted hazard ratio, 0.616; 95% confidence interval, 0.493–0.770), thus identifying inhibitors of this Alu replication cycle shunt as potential therapies for a major cause of blindness.

Significance Alu elements, comprising more than 10% of the human genome, propagate via retrotransposition. This genomic expansion requires enzymatic activity of L1 that reverse transcribes Alu RNA into Alu cDNA in the nucleus. We report Alu also undergoes L1-mediated reverse transcription via self-priming in the cytoplasm independent of retrotransposition, providing evidence of human DNA synthesis in this cellular compartment. This newly discovered shunt molecule in the Alu replication cycle also induces death of the retinal pigmented epithelium, a hallmark of atrophic age-related macular degeneration. A Big Data Archeology analysis of multiple health insurance databases reveals that use of FDA-approved nucleoside reverse transcriptase inhibitors is associated with protection against macular degeneration, identifying a repurposing candidate for this blinding disease.

Anterior segment optical coherence tomography (AS-OCT) originally derived from posterior segment OCT. By changing the wavelength of the light source to a longer range, 1,000–1,300 nm, which is suboptimal for posterior segment imaging but more suitable to visualize anterior eye structures, the OCT devices specifically dedicated to anterior ocular segment were developed. Evolving from time-domain, Fourier-domain, spectral-domain, and to swept-source technologies, the current AS-OCT is widely accepted as a sophisticated tool that provides high-resolution three-dimensional images of the anterior segment ocular features, including the tear film, cornea, conjunctiva, subconjunctival space, sclera, rectus muscles, anterior chamber angle, crystalline lens, and anterior hyaloid membrane.

The conventional intensity-oriented OCT utilizes scattering information to evaluate morphological features of biological tissues. The new generation of OCT, polarization-sensitive OCT (PS-OCT), is capable of measuring the polarization properties of biological tissues, such as phase retardation, diattenuation, and optic-axis orientation. Thus, PS-OCT assesses qualitative characteristics of ocular structures, including arrangement of collagen fibers and presence of fibrotic changes. This chapter describes the basic concept of its technological background, the instrumentation of anterior PS-OCT, and its applications to the field of cornea and glaucoma research. In corneal research, PS-OCT is highly useful to detect the extremely early changes in the cornel stroma of keratoconus before topographical changes in the anterior and posterior corneal surfaces appear. Corneal dystrophy and degeneration can also be evaluated with PS-OCT. In glaucoma research, fibrotic changes within the bleb after filtering surgery detected by PS-OCT may be a prognostic factor of the subsequent bleb functions. Microstructures at the anterior chamber angle, such as trabecular meshwork, are the target of PS-OCT evaluations.

Label-free metabolic imaging of non-alcoholic fatty liver disease (NAFLD) mouse liver is demonstrated ex vivo by dynamic optical coherence tomography (OCT). The NAFLD mouse is a methionine choline-deficient (MCD)-diet model, and two mice fed the MCD diet for 1 and 2 weeks are involved in addition to a normal-diet mouse. The dynamic OCT is based on repeating raster scan and logarithmic intensity variance (LIV) analysis that enables volumetric metabolic imaging with a standard-speed (50,000 A-lines/s) OCT system. Metabolic domains associated with lipid droplet accumulation and inflammation are clearly visualized three-dimensionally. Particularly, the normal-diet liver exhibits highly metabolic vessel-like structures of peri-vascular hepatic zones. The 1-week MCD-diet liver shows ring-shaped highly metabolic structures formed with lipid droplets. The 2-week MCD-diet liver exhibits fragmented vessel-like structures associated with inflammation. These results imply that volumetric LIV imaging is useful for visualizing and assessing NAFLD abnormalities.

Geographic atrophy is a blinding form of age-related macular degeneration characterized by death of the retinal pigmented epithelium (RPE). In this disease, the RPE displays evidence of DICER1 deficiency, resultant accumulation of endogenous Alu retroelement RNA, and NLRP3 inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human cell culture and in mouse models is driven by a non-canonical inflammasome pathway that results in activation of caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β (IFN-β) production and gasdermin D-dependent interleukin-18 (IL-18) secretion. Reduction of DICER1 levelsor accumulation of Alu RNA triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, IFN-β, and cGAS levels are elevated in the RPE of human eyes with geographic atrophy. Collectively, these data highlight an unexpected role for cGAS in responding to mobile element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial damage-induced inflammasome activation, expand the immune sensing repertoire of cGAS and caspase-4 to non-infectious human disease, and identify new potential targets for treatment of a major cause of blindness.

Significance DICER1 processes micro-RNAs into their bioactive forms and metabolizes RNAs from short interspersed nuclear element genetic repeats, principally Alu RNAs in humans. DICER1 deficiency is implicated in retinal pigmented epithelium (RPE) degeneration in atrophic age-related macular degeneration (AMD). Here, we report that three independent mouse models of DICER1 deficiency develop RPE degeneration and aberrant choroidal and retinal neovascularization (CRNV), both hallmarks of advanced AMD. These pathologies were dependent on inflammatory caspases 1 and 11 and the signaling adaptor MyD88. We observed reduced DICER1 abundance in a separate model of spontaneous CRNV and developed an adenoassociated vector-mediated DICER1 delivery construct, which reduced the severity of established spontaneous CRNV. Thus, persistent deficiency in DICER1 results in RPE degeneration and CRNV., Degeneration of the retinal pigmented epithelium (RPE) and aberrant blood vessel growth in the eye are advanced-stage processes in blinding diseases such as age-related macular degeneration (AMD), which affect hundreds of millions of people worldwide. Loss of the RNase DICER1, an essential factor in micro-RNA biogenesis, is implicated in RPE atrophy. However, the functional implications of DICER1 loss in choroidal and retinal neovascularization are unknown. Here, we report that two independent hypomorphic mouse strains, as well as a separate model of postnatal RPE-specific DICER1 ablation, all presented with spontaneous RPE degeneration and choroidal and retinal neovascularization. DICER1 hypomorphic mice lacking critical inflammasome components or the innate immune adaptor MyD88 developed less severe RPE atrophy and pathological neovascularization. DICER1 abundance was also reduced in retinas of the JR5558 mouse model of spontaneous choroidal neovascularization. Finally, adenoassociated vector-mediated gene delivery of a truncated DICER1 variant (OptiDicer) reduced spontaneous choroidal neovascularization in JR5558 mice. Collectively, these findings significantly expand the repertoire of DICER1 in preserving retinal homeostasis by preventing both RPE degeneration and pathological neovascularization.

Purpose: Polarization-sensitive optical coherence tomography (PS-OCT) can detect and evaluate scar fibrosis of the filtering blebs after glaucoma surgery. Although the change in phase retardation reportedly reflects bleb function, quantitative assessment of phase retardation in ocular tissues has not been conducted. We aimed to establish quantitative methods to investigate changes in phase retardation in the blebs after surgery using PS-OCT. Methods: Twenty-two blebs of 22 patients who had undergone glaucoma filtration surgery were consecutively examined for 4 months. Phase retardation was measured by PS-OCT and quantitatively analyzed to evaluate its relationship with bleb function based on intraocular pressure and medication use. Cross-sectional re-evaluation was also performed for a previous data set of 153 blebs of 122 patients. Results: In consecutive measurements, all blebs showed a low phase retardation value and good bleb function until 2 weeks. One month postoperatively, the phase retardation value was significantly increased, whereas bleb function was still good. The phase retardation value at 1 month postoperatively was significantly correlated with bleb function at 4 months postoperatively. While 55.6% of blebs with a high phase retardation value at 1 month subsequently lost function, only 7.7% with a low phase retardation value had bleb failure. In the cross-sectional re-evaluation, the quantitatively evaluated phase retardation value was highly correlated with bleb function (β = 0.770, P < 0.001). Conclusions: An increase in phase retardation preceded deterioration of bleb function. The change in phase retardation may provide a prognostic metric for bleb function in the early stage after surgery.

We present optical coherence tomography (OCT)-based tissue dynamics imaging method to visualize and quantify tissue dynamics such as subcellular motion based on statistical analysis of rapid-time-sequence OCT signals at the same location. The analyses include logarithmic intensity variance (LIV) method and two types of OCT correlation decay speed analysis (OCDS). LIV is sensitive to the magnitude of the signal fluctuations, while OCDSs including early- and late-OCDS (OCDS e and OCDS l , respectively) are sensitive to the fast and slow tissue dynamics, respectively. These methods were able to visualize and quantify the longitudinal necrotic process of a human breast adenocarcinoma spheroid and its anti-cancer drug response. Additionally, the effects of the number of OCT signals and the total acquisition time on dynamics imaging are examined. Small number of OCT signals, e.g., five or nine suffice for dynamics imaging when the total acquisition time is suitably long.

Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P, Inflammasome activation may contribute to type 2 diabetes, but whether targeting inflammasome is beneficial is unclear. Here the authors show that repurposing nucleoside reverse transcriptase inhibitors for inhibiting inflammasome activation is associated with reduced diabetes development in people and improves insulin sensitivity in experimental settings.

This paper presents the theory and numerical implementation of a maximum likelihood estimator for local phase retardation (i.e., birefringence) measured using Jones-matrix-based polarization sensitive optical coherence tomography. Previous studies have shown conventional mean estimations of phase retardation and birefringence are significantly biased in the presence of system noise. Our estimator design is based on a Bayes' rule that relates the distributions of the measured birefringence under a particular true birefringence and the true birefringence under a particular measured birefringence. We used a Monte-Carlo method to calculate the likelihood function that describes the relationship between the distributions and numerically implement the estimator. Our numerical and experimental results show that the proposed estimator was asymptotically unbiased even with low signal-to-noise ratio and/or for the true phase retardations close to the edge of the measurement range. The estimator revealed detailed clinical features when applied to the in vivo anterior human eye.

The relationship between scleral birefringence and biometric parameters of human eyes in vivo is investigated. Scleral birefringence near the limbus of 21 healthy human eyes was measured using polarization-sensitive optical coherence tomography. Spherical equivalent refractive error, axial eye length, and intraocular pressure (IOP) were measured in all subjects. IOP and scleral birefringence of human eyes in vivo was found to have statistically significant correlations (r = -0.63, P = 0.002). The slope of linear regression was -2.4 × 10(-2) deg/μm/mmHg. Neither spherical equivalent refractive error nor axial eye length had significant correlations with scleral birefringence. To evaluate the direct influence of IOP to scleral birefringence, scleral birefringence of 16 ex vivo porcine eyes was measured under controlled IOP of 5-60 mmHg. In these ex vivo porcine eyes, the mean linear regression slope between controlled IOP and scleral birefringence was -9.9 × 10(-4) deg/μm/mmHg. In addition, porcine scleral collagen fibers were observed with second-harmonic-generation (SHG) microscopy. SHG images of porcine sclera, measured on the external surface at the superior side to the cornea, showed highly aligned collagen fibers parallel to the limbus. In conclusion, scleral birefringence of healthy human eyes was correlated with IOP, indicating that the ultrastructure of scleral collagen was correlated with IOP. It remains to show whether scleral collagen ultrastructure of human eyes is affected by IOP as a long-term effect.

To investigate the role of reactive oxygen species (ROS) in retinal development during the early postnatal stage of rd1 mice.Development of the three retinal vascular layers of C57BL/6 J (WT) and C3H/HeN (rd1) mice was evaluated from 9th postnatal day (P9) to P21. Retinal ROS production was semi-quantitatively measured using dihydroethidium fluorescence. Mice were treated with intraperitoneal injections of 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) at a dose of 275 mg/kg body weight, and PBS as the control from P3 to P8.Rd1 mice showed retardation of retinal vascular development in the deep layer at P9. No significant difference was observed in the outer nuclear layer thickness of rd1 and WT mice. ROS production in the outer nuclear layer of rd1 mice was significantly higher than that in the outer nuclear layer of WT mice at P9, P13, and P17 (P .05). TEMPOL facilitated the development of the deep vascular layer when compared with injection of PBS.Retardation of retinal vascular development is observed in rd1 mice; ROS is partially responsible for this finding. When using rd1 mice, we should be aware of this difference in comparison to other retinal degeneration animal models and human pathophysiological changes.

The aim of this study was to use conventional visual acuity measurements to quantify the functional visual acuity (FVA) in eyes with successfully treated amblyopia, and to compare the findings with those for contralateral normal eyes. Nineteen patients (7 boys, 12 girls; age 7.5 ± 2.2 years) with successfully treated unilateral amblyopia and the same conventional decimal visual acuity in both eyes (better than 1.0) were enrolled. FVA, the visual maintenance ratio (VMR), maximum and minimum visual acuity, and the average response time were recorded for both eyes of all patients using an FVA measurement system. The differences in FVA values between eyes were analyzed. The mean LogMAR FVA scores, VMR (p

Purpose The fibrosis score is a new diagnostic score that we have developed to evaluate the function of bleb structures after glaucoma filtration surgery using polarization-sensitive optical coherence tomography (PS-OCT). This study aims to assess the efficacy of the fibrosis score in discriminating nonfunctional from the functional blebs. Methods A total of 20 patients who had undergone glaucoma filtration surgery were imaged at different time periods after surgery using PS-OCT. Birefringence tomography of blebs was obtained from PS-OCT, and the fibrosis score was computed for each patient. The fibrosis score is defined as the area of occupation of high birefringence area in the conjunctiva. The blebs were classified as functional or nonfunctional according to the IOP and the application of medication. The power of the fibrosis score to discriminate nonfunctional blebs from functional blebs was evaluated. Results The difference in the mean fibrosis score between the functional and nonfunctional bleb group was statistically significant. The fibrosis score showed good ability to discriminate nonfunctional from functional blebs. The area under the receiver operating characteristic curve was 0.82. The best combination of the sensitivity and specificity was 67% and 100%, respectively, for classifying nonfunctional cases. Conclusions The fibrosis score showed a high ability to discriminate nonfunctional from functional blebs. Polarization-sensitive OCT is a noninvasive technique that provides not only the fibrosis score but also standard structural tomography. It can be a comprehensive tool for longitudinal evaluation after filtration surgery for glaucoma.

This study examines how nontraditional financial policies were implemented in Japan from the late 1990s to the early 2000s by looking at the differences between the zero interest rate policy and quantitative easing policy. During this time, the Bank of Japan adopted an unprecedented ultra-low interest rate policy. Orthodox financial policies had become ineffective because of the liquidity trap. However, under increasing instability in the financial markets, this radical financial policy proved to be somewhat effective as a credit-easing measure. In this analysis, I focus on the fact that a difference between the high and low daytime call rates (the spread) emerges as a reflection of the risk premium, and I examine how that spread differed during the zero interest rate period and the quantitative easing period. Not only did the ultra-low interest rate policy cause the short-term interest target rate to approach 0 percent, but it was also somewhat effective at reducing the size of the spread in the call mar...

To evaluate the repeatability and reproducibility of anterior chamber volume (ACV) measurements using swept-source 3-dimensional corneal and anterior segment optical coherence tomography (CAS-OCT) and dual Scheimpflug imaging.Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.Nonrandomized clinical trial.Measurements were taken in normal eyes (subject group) and in eyes with primary angle closure (PAC) (patient group). In the subject group, the entire ACV and the central 8.0 mm diameter ACV were measured using CAS-OCT and dual Scheimpflug imaging. In the patient group, the entire ACV and 8.0 mm ACV were measured using CAS-OCT. The coefficient of variation and intraclass correlation coefficient (ICC) were calculated to evaluate repeatability and reproducibility, and the correlation between the 2 devices was assessed.In the subject group, the mean 8.0 mm ACV was 110.14 mm(3) ± 12.57 (SD) using CAS-OCT and 114.51 ± 14.69 mm(3) using Scheimpflug imaging; there was a significant linear correlation (r = 0.878, P.0001). The mean entire ACV on CAS-OCT was 165.15 ± 29.29 mm(3). The ICCs of the 8.0 mm and entire ACV measurements were greater than 0.94. The coefficients of repeatability and reproducibility of the 8.0 mm ACV and entire ACV measurements were less than 5%. In the patient group, the 8.0 mm and entire ACV measurements showed good reproducibility and repeatability.The CAS-OCT method allowed noninvasive measurement of the entire ACV with sufficient repeatability and reproducibility. The 8.0 mm ACV measurements with CAS-OCT and Scheimpflug imaging were comparable.

We present a case series of cornea and anterior segment disorders investigated by an office-based polarization-sensitive optical coherence tomography (PS-OCT). Blebs of glaucoma patients treated by trabeculectomy, and corneas of keratoconus and keratoplasty patients were measured by PS-OCT. Birefringence formations in trabeculectomy bleb were measured in 1 control eye and 3 eyes of trabeculectomy model rabbits. Polarization insensitive scattering OCT and the depth-resolved birefringence were measured simultaneously by PS-OCT. Abnormal birefringence was observed in keratoconus cases with advanced thinning and with a rupture of Descemet's membrane. The graft-host interface of the keratoplasty case showed abnormal birefringence. The appearance of abnormal birefringence in the cornea was likely to be an indication of cross-linking of collagen fibrils. The measurement of rabbit showed abnormal birefringence in the scarring eyes. Wide regions of strong birefringence were observed in the eyes of trabeculectomy patients who had high intraocular pressure. Visualization of scarring in bleb by PS-OCT may be useful for the planning of secondary surgery. PS-OCT showed promising for the study and diagnosis diseases related to abnormal fibrous tissues of the cornea and anterior eye segment.

To evaluate the repeatability and reproducibility of central corneal thickness (CCT), anterior chamber depth (ACD), and anterior chamber width (ACW) measurements using 3-dimensional (3-D) corneal and anterior segment optical coherence tomography (CAS-OCT) and 2-dimensional (2-D) anterior segment OCT (AS-OCT).Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.Nonrandomized clinical trial.The CCT, ACD, and ACW were measured in normal eyes using a prototype 3-D swept-source CAS-OCT device and a 2-D time-domain AS-OCT device (Visante). The coefficient of repeatability and reproducibility and the intraclass correlation coefficient (ICC) were calculated to evaluate the repeatability and reproducibility of the measurements.Eighty-five eyes (85 subjects) were evaluated. The mean CCT measurement was 557.5 μm ± 40.5 (SD) with CAS-OCT and 556.4 ± 39.4 μm with AS-OCT; the mean ACD measurement, 3.13 ± 0.40 mm and 3.16 ± 0.39 mm, respectively; and the mean ACW, 11.80 ± 0.47 mm and 11.79 ± 0.49 mm, respectively. There was no statistically significant difference in CCT or ACW measurements between the 2 devices (P.05, Wilcoxon signed rank test). Although the ACD measurements were significantly different (P.0001), the difference was small (0.03 mm). Significant linear correlations were found between the measurements of the 2 devices (P.0001). The ICC was greater than 0.99 for CAS-OCT and greater than 0.96 for AS-OCT.Corneal and anterior segment OCT and AS-OCT provided comparable and well-correlated anterior ocular biometric measurements, with sufficient repeatability and reproducibility.

Polarization-sensitive optical coherence tomography (PS-OCT) allows the recording of depth-resolved polarimetric measurements. It has been reported that phase retardation and local birefringence images can noninvasively detect fibrotic area in blebs after glaucoma surgery. Evaluation of scar fibrosis in blebs is important not only for predicting bleb function, but also for planning revision trabeculectomy. Herein, we characterize the intensity, phase retardation, and local birefringence images of blebs using PS-OCT. A total of 85 blebs from 85 patients who had undergone trabeculectomy were examined. Both phase retardation and local birefringence images detected fibrotic changes in blebs after glaucoma surgery. Phase retardation images detected slight fibrotic change during the early stage after surgery, whereas local birefringence images showed localized fibrotic tissue. There are two main patterns of local birefringence image changes in blebs: plate-like birefringence changes and diffuse changes. The area of plate-like birefringence change was significantly larger in poorly functioning blebs and is thus correlated with bleb function. These data suggest that the plate-like fibrotic change evaluation by PS-OCT may be useful not only for noninvasive evaluation of fibrotic scar tissue in blebs, but also for developing strategies for revision trabeculectomy.

Aim: To evaluate the relationship between vision-related quality of life (VR-QOL) and visual function in patients undergoing vitrectomy, gas tamponade and cataract surgery for macular hole (MH). Methods: The 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was self-administered by 32 patients with MH (age 66.2 (SD 5.4) years) preoperatively and at 3 months postoperatively. Clinical data were collected, including logarithm of minimum angle of resolution (logMAR) best corrected visual acuity (BCVA), severity of metamorphopsia and letter contrast sensitivity. The severity of metamorphopsia was evaluated by the M-Charts. MH index was measured using optical coherence tomography. The presence and severity of cataract were graded using the Lens Opacities Classification System III reference standards. Multiple regression analysis was performed to investigate the relationship between various explanatory variables and VFQ-25 questionnaire scores. Explanatory variables tested were the severity of metamorphopsia, visual acuity, letter contrast sensitivity, MH index and grade of cataract. Results: Vitrectomy for MH significantly improved VFQ-25 composite score as well as subscale scores, including general vision, near activities, distance activities, social functioning, mental health and dependency (p

To evaluate anterior ocular biometry by comparing the measurements of central corneal thickness (CCT) and anterior chamber depth (ACD) with 3-dimensional corneal and anterior segment optical coherence tomography (CAS-OCT) and other methods.Cross-sectional study.Forty eyes of 40 normal subjects.The CCT was measured by 4 methods (CAS-OCT, Scheimpflug camera, scanning-slit topography, and ultrasonic pachymetry), and the ACD was measured by 3 methods (CAS-OCT, Scheimpflug camera, and scanning-slit topography). The anterior chamber volume (ACV) was calculated with CAS-OCT. Repeatability and reproducibility of CAS-OCT measurements were evaluated.The CCT and ACD were measured and compared between devices. The ACV was calculated with CAS-OCT. Coefficient of variation and intraclass correlation coefficient (ICC) were calculated to evaluate repeatability and reproducibility of CAS-OCT measurements.The mean CCT was 547.0+/-39.0, 590.0+/-39.8, 525.0+/-45.0, and 545.0+/-40.3 microm with CAS-OCT, Scheimpflug camera, scanning-slit topography, and ultrasonic pachymetry, respectively. Significant differences were observed among the 4 methods (P0.0001; 1-way analysis of variance [ANOVA]). The CCT measured with Scheimpflug camera was significantly larger than those measured with the other methods (P0.0001; Bonferroni multiple comparison), but there was no significant difference among the other 3 methods. The mean ACD was 3.01+/-0.47, 3.04+/-0.52, and 2.88+/-0.50 mm with CAS-OCT, Scheimpflug camera, and scanning-slit topography, respectively. There was no significant difference among the 3 methods (P = 0.678; 1-way ANOVA). A significant linear correlation in CCT and ACD were observed between CAS-OCT and other methods (all P0.0001). The mean ACV calculated with CAS-OCT was 169.7+/-23.1 mm(3). The coefficient of repeatability and reproducibility of CCT and ACD measurements were5% and ICCs were0.98.The CCT measurements were comparable among CAS-OCT, ultrasonic pachymetry, and scanning-slit topography, but Scheimpflug camera yielded a significantly higher CCT value. There was no significant difference in ACD measurements among CAS-OCT, Scheimpflug camera, and scanning-slit topography. The ACV was noninvasively measured by CAS-OCT.The authors have no proprietary or commercial interest in any materials discussed in this article.

Polarization sensitive optical coherence tomography (PS-OCT) is a functional extension of OCT that contrasts the polarization properties of tissues. It has been applied to ophthalmology, cardiology, etc. Proper quantitative imaging is required for a widespread clinical utility. However, the conventional method of averaging to improve the signal to noise ratio (SNR) and the contrast of the phase retardation (or birefringence) images introduce a noise bias offset from the true value. This bias reduces the effectiveness of birefringence contrast for a quantitative study. Although coherent averaging of Jones matrix tomography has been widely utilized and has improved the image quality, the fundamental limitation of nonlinear dependency of phase retardation and birefringence to the SNR was not overcome. So the birefringence obtained by PS-OCT was still not accurate for a quantitative imaging. The nonlinear effect of SNR to phase retardation and birefringence measurement was previously formulated in detail for a Jones matrix OCT (JM-OCT) [1]. Based on this, we had developed a maximum a-posteriori (MAP) estimator and quantitative birefringence imaging was demonstrated [2]. However, this first version of estimator had a theoretical shortcoming. It did not take into account the stochastic nature of SNR of OCT signal. In this paper, we present an improved version of the MAP estimator which takes into account the stochastic property of SNR. This estimator uses a probability distribution function (PDF) of true local retardation, which is proportional to birefringence, under a specific set of measurements of the birefringence and SNR. The PDF was pre-computed by a Monte-Carlo (MC) simulation based on the mathematical model of JM-OCT before the measurement. A comparison between this new MAP estimator, our previous MAP estimator [2], and the standard mean estimator is presented. The comparisons are performed both by numerical simulation and in vivo measurements of anterior and posterior eye segment as well as in skin imaging. The new estimator shows superior performance and also shows clearer image contrast.

Retinal hypoxia plays a crucial role in ocular neovascular diseases, such as diabetic retinopathy, retinopathy of prematurity, and retinal vascular occlusion. Fluorescein angiography is useful for identifying the hypoxia extent by detecting non-perfusion areas or neovascularization, but its ability to detect early stages of hypoxia is limited. Recently, in vivo fluorescent probes for detecting hypoxia have been developed; however, these have not been extensively applied in ophthalmology. We evaluated whether a novel donor-excited photo-induced electron transfer (d-PeT) system based on an activatable hypoxia-selective near-infrared fluorescent (NIRF) probe (GPU-327) responds to both mild and severe hypoxia in various ocular ischemic diseases animal models. The ocular fundus examination offers unique opportunities for direct observation of the retina through the transparent cornea and lens. After injection of GPU-327 in various ocular hypoxic diseases of mouse and rabbit models, NIRF imaging in the ocular fundus can be performed noninvasively and easily by using commercially available fundus cameras. To investigate the safety of GPU-327, electroretinograms were also recorded after GPU-327 and PBS injection. Fluorescence of GPU-327 increased under mild hypoxic conditions in vitro. GPU-327 also yielded excellent signal-to-noise ratio without washing out in vivo experiments. By using near-infrared region, GPU-327 enables imaging of deeper ischemia, such as choroidal circulation. Additionally, from an electroretinogram, GPU-327 did not cause neurotoxicity. GPU-327 identified hypoxic area both in vivo and in vitro.

Purpose Polarization-sensitive optical coherence tomography (PS-OCT) can evaluate internal tissue structures of the cornea, such as collagen fibers, by phase retardation measurement. In this study, we assessed the repeatability of corneal phase retardation measurements using anterior segment PS-OCT. Methods A total of 173 eyes of 173 patients were measured using PS-OCT. In total, 58 eyes of young subjects with normal corneas, 28 eyes of old subjects with normal corneas, 26 eyes with corneal dystrophy or degeneration, 37 eyes with corneal transplantation, and 24 eyes with keratoconus were evaluated. The 3-mm diameter average of en face phase retardation of the posterior corneal surface was examined using PS-OCT. To evaluate the repeatability, intraclass correlation coefficients (ICCs) were calculated for intraobserver repeatability and interobserver repeatability analysis. Results Polarization-sensitive OCT showed good repeatability for corneal measurements. Intraclass correlation coefficients of intraobserver and interobserver repeatability of all the subjects were 0.989 and 0.980, respectively. Intraclass correlation coefficients of the intraobserver for each group, that is, young and old subjects with normal cornea, cornea dystrophy/degeneration, corneal transplantation, and keratoconus, were 0.961, 0.975, 0.984, 0.978, and 0.996, respectively. Interobserver ICCs for the above-mentioned respective groups were 0.952, 0.964, 0.988, 0.959, and 0.975, respectively. Conclusions Polarization-sensitive OCT showed good repeatability for phase retardation measurements of central corneas not only for normal corneas, but also for various diseased corneas. Polarization-sensitive OCT might be useful for evaluating corneal phase retardation, which is one of the parameters that defines birefringence.

PURPOSE: Evaluation of bleb morphology using anterior segment optical coherence tomography (OCT) can offer important information regarding bleb function after glaucoma surgery. However, analysis of tissue properties, such as scar fibrosis of blebs, is difficult with conventional OCT. The birefringence of the blebs as susceptible measure of fibrosis scar was evaluated using polarization-sensitive OCT (PS-OCT) and its relation with bleb function was assessed. METHODS: One hundred and fifty-three blebs of 122 patients that had undergone trabeculectomy or an Ex-Press tube shunt were examined. Also, in 14 blebs of 12 patients, consecutive measurements were performed for 2 months after surgery. The birefringence of blebs was evaluated by measuring alteration of phase retardation using PS-OCT. Functionality of the bleb was classified according to IOP and medication. The bleb morphology in terms of size and characteristics was evaluated using three-dimensional (3D) cornea and anterior segment OCT. RESULTS: The alteration of phase retardation of blebs had the largest impact on bleb functionality than bleb morphology as shown by multiple regression analysis. In consecutive measurements, no blebs showed abnormal phase retardation until 1 week after surgery. Some blebs showed partial increase of phase retardation at 1 month after surgery. CONCLUSIONS: Intrableb fibrosis can be noninvasively evaluated with PS-OCT. Evaluation of birefringence by measuring phase retardation alterations using PS-OCT suggests new approaches for the postoperative management of glaucoma blebs regarding antifibrotic treatment for preventing IOP increases.

To evaluate the ability of parameters measured by three-dimensional (3D) corneal and anterior segment optical coherence tomography (CAS-OCT) and a rotating Scheimpflug camera combined with a Placido topography system (Scheimpflug camera with topography) to discriminate between normal eyes and forme fruste keratoconus.Forty-eight eyes of 48 patients with keratoconus, 25 eyes of 25 patients with forme fruste keratoconus and 128 eyes of 128 normal subjects were evaluated. Anterior and posterior keratometric parameters (steep K, flat K, average K), elevation, topographic parameters, regular and irregular astigmatism (spherical, asymmetry, regular and higher-order astigmatism) and five pachymetric parameters (minimum, minimum-median, inferior-superior, inferotemporal-superonasal, vertical thinnest location of the cornea) were measured using 3D CAS-OCT and a Scheimpflug camera with topography. The area under the receiver operating curve (AUROC) was calculated to assess the discrimination ability. Compatibility and repeatability of both devices were evaluated.Posterior surface elevation showed higher AUROC values in discrimination analysis of forme fruste keratoconus using both devices. Both instruments showed significant linear correlations (p0.05, Pearson's correlation coefficient) and good repeatability (ICCs: 0.885-0.999) for normal and forme fruste keratoconus.Posterior elevation was the best discrimination parameter for forme fruste keratoconus. Both instruments presented good correlation and repeatability for this condition.

To investigate the tissue properties of keratoconic and normal corneas in vivo by using polarization-sensitive optical coherence tomography (PS-OCT), and to evaluate early keratoconus by the area under the receiver operating characteristic curve (AUROC) and Mahalanobis distance analysis.Thirty-one eyes of 20 patients with keratoconus, 7 eyes of 7 patients with keratoconus suspect, and 25 eyes of 25 normal subjects were investigated by PS-OCT and corneal and anterior segment (CAS)-OCT. Average of en face phase retardation of the posterior surface of the cornea, curvature, videokeratographic parameters, regular and irregular astigmatism, pachymetry map, and elevation were measured. The AUROC of each parameter was calculated to evaluate the diagnostic power to detect keratoconus and keratoconus suspect.While in normal controls, the center of the en face phase retardation map showed low and homogeneous birefringence, in keratoconic corneas the birefringence increased with disease severity. Some keratoconus suspects had apparent high birefringence values without displaying morphologic signs of keratoconus in the anterior surface. The phase retardation values for normal, keratoconus suspect, and keratoconus subjects were, respectively, 0.20 ± 0.06, 0.35 ± 0.06, and 0.50 ± 0.14 radians in 3 mm diameter and 0.29 ± 0.22, 0.33 ± 0.13, and 0.74 ± 0.45 radians in 6 mm diameter. Outer morphological parameters such as curvature, videokeratographic parameters, regular and irregular astigmatism, and elevation showed high AUROCs for discriminating keratoconus from normal controls. On the other hand, using Mahalanobis distance, the AUROC of phase retardation, which represents microstructural properties of tissue, showed high value (0.989-1.000) for discriminating between keratoconus suspects and normal controls.Average of en face phase retardation of the posterior surface of the cornea was increased in keratoconus patients due to changes in the lamellar structure of collagen fibers. Phase retardation was sensitive with regard to discriminating keratoconus suspect and might be useful for detecting very early or even subclinical keratoconus.

Purpose: We conducted an in vivo study using Dutch pigmented rabbit eyes to test the usefulness of polyethylene glycol (PEG) sealant for the closure of sutureless sclerotomies in microincisional vitrectomy surgery (MIVS). Methods: Three-port, 23-gauge vitrectomy was performed on rabbit eyes. After air leakage was confirmed by the application of 0.625% povidone–iodine at the sclerotomy site, PEG sealant was subconjunctivally injected using a 27-gauge needle through conjunctival incisions to cover the sclerotomy wounds, following which it was polymerized by the application of xenon light for 60 seconds. Ophthalmological examinations and intraocular pressure measurements were conducted the day before and 1, 3, 5, and 7 days after surgery. The eyes were enucleated for histological evaluation 7 days after surgery. Results: PEG sealant was rapidly polymerized by the application of xenon light after subconjunctival injection, and it firmly sealed the sclerotomies without air leakage, as confirmed by povidone–iodine dropping, in all cases. Conjunctival and scleral wounds closed with PEG sealant were successfully attached and remained intact till the end of the follow-up period. There was no sign of postoperative hypotony or infection in any eye, and no adverse effects of PEG sealant were found. In histological examination, linear scar formation and eosinophilic staining of collagen fibers were observed at the sclerotomy sites, while the sclerotomy tunnels appeared tightly closed. Conclusions: PEG sealant can be useful for the closure of sutureless 23-gauge vitrectomy incisions in rabbits. Translational Relevance: The PEG sealant may become an effective option for closing vitrectomy incisions including pediatric cases.

A novel foreign-metal detection-system for wireless power transfer (WPT) is described. Foreign metal was heated only when placed between the primary coil and the secondary coil. By having the metal in that position, the quality factor of the secondary coil (Q 2 ) decreased rather than other parameters, so Q 2 was a suitable parameter for detecting the metal. We developed s Q 2 measurement circuit that works without any battery in the secondary device, and also developed a prototype WPT system with the Q 2 measurement circuit. Using this system, foreign metal that might be heated could be detected before heating.

Polarization-sensitive optical coherence tomography (PS-OCT) is known to be advantageous because of its additional tissue-specific contrast of the anterior eye. So far, this advantage has been shown only qualitatively. We evaluate the improved visibility afforded by 3-D PS corneal and anterior eye segment OCT (PS-CAS-OCT) in visualizing the trabecular meshwork (TM) based on statistical evidences. A total of 31 normal subjects participated in this study. The anterior eye segments of both the eyes of the subjects are scanned using a custom-made PS-CAS-OCT and the standard-scattering OCT (S-OCT) and polarization-sensitive phase-retardation OCT (P-OCT) images are obtained. Three graders grade the visibility of the TM using a four-leveled grading system. The intergrader agreement, intermodality differences, and interquadrant dependence of visibility are statistically examined. All three of three combinations of graders show substantial agreement in visibility with P-OCT (ρ = 0.74, 0.70, and 0.68, Spearman's correlation), while only one of three shows substantial agreement with S-OCT (ρ = 0.72). Significant dependence of the visibility on the modality (S-OCT versus P-OCT) and quadrants are found by the analysis of variance. A subsequent Wilcoxon signed-rank test reveals significantly improved visibility. PS-CAS-OCT may become a useful tool for screening angle-closure glaucoma.