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Purpose: To quantify the total eye astigmatism that is not accounted for by measurement of anterior corneal astigmatism and posterior corneal astigmatism and knowledge of intraocular lens (IOL) astigmatism and assess whether it is correlated with candidate sources of or correlates with leftover astigmatism., Methods: Vector subtraction of anterior corneal, posterior corneal, and IOL astigmatism from total eye astigmatism as represented by spectacle astigmatism to yield a value of "leftover" astigmatism that is neither corneal nor lenticular. This value was derived in a series of eyes following cataract surgery. This novel entity was examined for correlation with candidate sources of or correlates with leftover astigmatism., Results: In 103 pseudophakic eyes with known IOL toricity, mean leftover astigmatism was 0.71 ± 0.43 diopters. This was significantly correlated with against-the-rule anterior corneal astigmatism ( P < .001)., Conclusions: Leftover astigmatism is clinically substantial. Because it is included in IOL cylinder power calculations based on refractive outcome, it may explain why methods of IOL cylinder power calculation using refractive outcome-based adjustments to anterior corneal astigmatism (previously described as adjustments for "posterior corneal astigmatism") are more successful than adjustment on the basis of measured posterior corneal astigmatism. [ J Refract Surg. 2022;38(9):559-564.] .

Purpose: 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., Methods: 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., Results: 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., Conclusion: 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.

Purpose: To compare "total keratometry" measurements with Goggin nomogram adjusted anterior keratometry (GNAK) for toric intraocular lens calculation., Methods: Routine biometry provided measured total keratometry values from which astigmatism was derived. The Goggin nomogram was applied to anterior keratometry values on the same eyes to provide nomogram-adjusted anterior keratometry values (GNAK) that estimate total corneal astigmatism. The agreement between total keratometry and GNAK was analyzed., Results: Overall, in 46 eyes there was no statistically significant difference between median GNAK and total keratometry power values (P = .746). No statistically significant difference remained in against-the-rule and oblique subgroup analyses. Absolute and signed steep axis of astigmatism was statistically significantly different for GNAK and total keratometry in the overall analysis (P < .001 and = .029, respectively) and for against-the-rule and oblique subgroup analyses. The with-the-rule subgroup showed a statistically significant difference in astigmatic power and no significant signed steep axis difference between GNAK and total keratometry., Conclusions: Total keratometry appears able to measure total corneal astigmatism to match closely (clinically and statistically) GNAK estimation of that parameter. This indicates that it would be safe and reasonable to use total keratometry data for planning of cataract surgery with toric IOLs. [J Refract Surg. 2018;34(8):521-526.]., (Copyright 2018, SLACK Incorporated.)

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.

Purpose: To report the safety and efficacy of descemetorhexis without grafting as a primary intervention in Fuchs dystrophy, and the use of a ROCK inhibitor, ripasudil as a salvage agent in failing cases., Methods: Twelve eyes of 11 patients underwent central descemetorhexis not exceeding 4 mm. All had Fuchs dystrophy-producing visual symptoms, requesting intervention. Exclusion criteria were a peripheral endothelial cell count <1000 and central edema. Corneal clearance and visual parameters were recorded monthly until corneal clearance was observed, then at intervals of 6 months. Cases failing to clear by month 2 were considered for salvage treatment. This consisted of treatment with 1 of 2 formulations of Rho-associated kinase inhibitor eye drops. Endothelial keratoplasty was planned as the final salvage procedure in unsuccessful cases., Results: Nine of 12 eyes cleared spontaneously between 2 and 6 months. One eye failed to clear by month 5 and topical Y-27632 was administered, without success. Endothelial keratoplasty was performed. In 2 eyes, healing stalled at 3 and 2 months. In both cases, topical ripasudil administered 6 times a day for 2 weeks resulted in complete corneal clearance. In cases achieving corneal clearance, best spectacle corrected visual acuity improved from a mean of 0.26 to 0.125 (logMAR) with subjective improvement in quality of vision., Conclusions: In Fuchs dystrophy with visual degradation due to central guttae, descemetorhexis without grafting is a viable procedure for visual rehabilitation. Careful patient selection is required, but the advent of topical ripasudil as a salvage agent suggests that a broader application of the surgery may be possible. Further study into the use of this agent is now needed.

Purpose: 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., Methods: 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., Result: 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., Conclusions: GPU-327 identified hypoxic area both in vivo and in vitro.

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.

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: To analyze the influence of simple myopic against-the-rule (ATR) and with-the-rule (WTR) astigmatism on uncorrected distance visual acuity (UDVA) in eyes after monofocal intraocular lens (IOL) implantation., Methods: Patients with a postoperative spherical refractive error within ±0.5 diopter (D) and a negative cylindrical refractive error ≥0.5 D were enrolled and divided into two groups: ATR or WTR astigmatism. Age, pupil size, spherical equivalent refractive error, spherical refractive error, cylindrical refractive power, UDVA, corrected distance visual acuity (CDVA) and ocular wavefront aberrations were compared between groups. Correlations between UDVA and other parameters were also examined within groups., Results: Twenty-five eyes (25 patients) with ATR astigmatism and 18 eyes (18 patients) with WTR astigmatism were evaluated. The logMAR UDVA was 0.30 ± 0.22 (mean ± SD) in the ATR group and 0.11 ± 0.15 in the WTR group, showing a significant difference between groups (P < 0.01). There were no significant differences in other parameters between groups. The UDVA was significantly correlated with spherical equivalent refractive error (r = -0.51, P < 0.01) and cylindrical refractive power (r = -0.48, P = 0.01) in the ATR group, but not in the WTR group. No other parameters were significantly correlated with UDVA in either group., Conclusion: After monofocal IOL implantation, UDVA in eyes with simple myopic ATR astigmatism was worse than in eyes with simple myopic WTR astigmatism. Additionally, UDVA was significantly influenced by cylindrical refractive power in eyes with ATR astigmatism, but not in eyes with WTR astigmatism.

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., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: To quantitatively assess the impact of subsurface nanoglistenings on forward light scattering and visual function., Setting: University of Tsukuba, Tsukuba, Japan., Design: Case-control study., Methods: Eyes with subsurface nanoglistenings and increased intraocular lens (IOL) surface light scattering and control eyes without subsurface nanoglistenings were evaluated. Forward light scattering was assessed with a double-pass device (Optical Quality Analysis System II) using the objective scatter index (OSI) as a quantitative parameter. Backward light scattering in the IOL surface was evaluated using Scheimpflug imaging (EAS-1000). The contrast sensitivity function was assessed as the area under the log contrast sensitivity function (AULCSF) measured with the Optec 6500 device. Correlations between the OSI, visual function, age, time after surgery, IOL power, and backward light scattering were analyzed., Results: In the study group, logMAR corrected distance visual acuity (CDVA) ranged from -0.176 to 0.045 (-0.06 ± 0.07 [SD]); no patient had a CDVA worse than 20/25. The OSI was significantly higher than in the control group (P=.0074) and correlated with CDVA (P=.0021), AULCSF photopic without glare (P=.0002) and with glare (P<.0001), and AULCSF mesopic without glare (P=.0038) and with glare (P=.0008). Multivariate analysis showed OSI was the only variable that correlated with CDVA and contrast sensitivity with glare. The OSI and age correlated with contrast sensitivity without glare (P<.05)., Conclusions: Eyes with subsurface nanoglistenings had increased forward light scattering but no deterioration in CDVA. Increases in forward light scattering correlated with reductions in visual acuity and contrast sensitivity, although both remained within their normal range., Financial Disclosures: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

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.

Purpose: To evaluate age-related changes in anterior, posterior, and total corneal astigmatism by comparing simulated keratometric astigmatism to total corneal astigmatism., Methods: Corneal topography of the anterior and posterior surfaces was evaluated using three-dimensional optical coherence tomography in 419 patients with normal eyes (218 men and 201 women) with ages ranging from 8 to 93 years (mean ± standard deviation: 49.5 ± 23.1 years). Keratometric astigmatism was calculated using the keratometric index (1.3375) and radius of the anterior corneal curvature; anterior and posterior corneal curvature measurements were used to calculate total corneal astigmatism., Results: The keratometric and total astigmatism were 1.08 ± 0.71 diopters (D) and 1.03 ± 0.69 D, respectively. Vector analysis revealed a mean difference between keratometric and total astigmatism of 0.24 ± 0.09 D, which showed a significant correlation to age (P < .0001). In eyes with with-the-rule astigmatism, keratometric astigmatism overestimated total astigmatism. In eyes with against-the-rule astigmatism, keratometric astigmatism underestimated total astigmatism., Conclusions: The anterior corneal surface shifts from with-the-rule to against-the-rule astigmatism with aging, whereas the posterior corneal surface remains as against-the-rule astigmatism in most cases. The variation in the anterior astigmatism is the most important factor contributing to this change. Total corneal astigmatism is a better predictor than keratometric astigmatism for selecting toric intraocular lenses., (Copyright 2014, SLACK Incorporated.)

Objective: 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., Methods: 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., Results: Posterior surface elevation showed higher AUROC values in discrimination analysis of forme fruste keratoconus using both devices. Both instruments showed significant linear correlations (p<0.05, Pearson's correlation coefficient) and good repeatability (ICCs: 0.885-0.999) for normal and forme fruste keratoconus., Conclusions: Posterior elevation was the best discrimination parameter for forme fruste keratoconus. Both instruments presented good correlation and repeatability for this condition.

Purpose: 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., Methods: 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., Results: 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., Conclusions: 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.

Despite its high prevalence, nonulcer dyspepsia is still difficult to study, due to the lack of adequate tools to measure significant outcomes. The objective of this study was to develop and validate a symptom-focused, disease-specific questionnaire to evaluate patients with nonulcer dyspepsia. For that, the questionnaire was carefully written following widely accepted terminology, so as to facilitate translation and validation in other languages and cultures. The questionnaire was developed using Rome I terminology for symptoms, which were evaluated according to their intensity, duration, and frequency when applicable. Thirty-one patients with nonulcer dyspepsia, as well as 31 sex-and age-matched volunteers without digestive problems were used to assess the internal consistency, reproducibility, responsiveness, content validity, and discriminant validity of the questionnaire. Another 31 functional dyspeptic patients were enrolled for assessment of criterion validity. Cronbach's alpha coefficient was 0.82. The intraclass correlation coefficient for the scores obtained 7 days apart was 0.86. The mean score obtained after 3 months of treatment was 16.4, vs. 23.03 at baseline (P = 0.001). Two blinded gastroenterologists agreed that the questionnaire adequately evaluated nonulcer dyspepsia. The median symptoms score for controls was 0, vs. 22.5 for dyspeptic patients (P = 0.001). An inverse correlation was observed between quality of life and dyspeptic symptoms (R = -0.28, P = 0.026). The proposed questionnaire has high degrees of both reproducibility and responsiveness. As this questionnaire was based on Rome I International Consensus terminology, it is expected that it will be easy to translate and validate.

S100B is an astrocytic calcium-binding protein which has been proposed as a biochemical marker of brain damage or dysfunction in acute and chronic diseases. We investigated whether serum S100B levels could be related to systemic lupus erythematosus (SLE) activity. Patients were grouped as having inactive SLE (ISLE), active SLE without central nervous system (CNS) involvement (ASLE), or active SLE with unequivocal neurologic or psychiatric manifestation (NPSLE). The control group consisted of age- and sex-matched healthy blood donors. S100B levels were determined using a luminescence immunoassay. All SLE groups had higher levels of serum S100B than the control group. Among the SLE groups, significantly higher levels of serum S100B protein were found in the NPSLE group than in the ISLE and ASLE groups, and there was no significant difference in S100B levels between the ISLE and ASLE groups. These preliminary results point to a putative relevance of serum S100B protein levels in SLE patients, specifically concerning CNS involvement present in this disease.