Sujin Hoshi

Keratoconus Diagnosis Using Anterior Segment Polarization-Sensitive Optical Coherence Tomography

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.

Noninvasive evaluation of phase retardation in blebs after glaucoma surgery using anterior segment polarization-sensitive optical coherence tomography.

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.

Time course of changes in aqueous flare intensity after vitrectomy for rhegmatogenous retinal detachment.

Purpose: To investigate the time course of changes in aqueous flare intensity after vitrectomy for rhegmatogenous retinal detachment (RD) and to determine the clinical factors related to an increase in aqueous flare. Methods: The present study included 22 unilateral patients with RD undergoing primary 20-gauge vitrectomy. Aqueous flare intensity was measured preoperatively and at 1 week, 2 weeks, 1 month, and 3, 6, and 12 months postoperatively using the laser flare meter. Results: Before vitrectomy, aqueous flare intensity was significantly higher in eyes with RD than in contralateral normal eyes. Vitrectomy increased aqueous flare intensity, and the peak was observed at the first postoperative week. Aqueous flare intensity decreased to a stable level at 3 months postoperatively but remained significantly higher than that of contralateral and preoperative eyes throughout the observation period. Clinical factors that were found to be significantly correlated with an increase in aqueous flare intensity included 1) before the surgical procedure: extent of RD and intraocular pressure, and 2) 3 months postoperatively: size of retinal breaks, number of laser photocoagulation spots, operation time, and performance of combined cataract surgery. Multiple regression analysis revealed that aqueous flare intensity at 3 months postoperatively had significant correlation with the size of retinal breaks (P < 0.005) and the number of laser photocoagulation spots (P < 0.05). Conclusion: Aqueous flare intensity after vitrectomy for RD decreased to a stable level at 3 months postoperatively but remained significantly higher than the normal level. The size of retinal breaks and the degree of surgical invasion were associated with the increase in aqueous flare.

Comparison of three-dimensional optical coherence tomography and combining a rotating Scheimpflug camera with a Placido topography system for forme fruste keratoconus diagnosis

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, Pearsons 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.

Three-dimensional volumetric human meibomian gland investigation using polarization-sensitive optical coherence tomography

Abstract. In this study, polarization-sensitive optical coherence tomography (PS-OCT) capable of providing polarization contrasts such as phase retardation and degree of polarization uniformity (DOPU) was used for visualizing human meibomian glands (MGs) and investigating morphological characteristics of them. Especially, with the help of the DOPU contrast, MGs were exclusively extracted from the volumetric OCT image. In vivo PS-OCT measurements were performed on the upper eyelids of different age groups. From these measurements, different age-dependent aspects of the MG structure were also observed. Based on these observations, it can be inferred that the PS-OCT system has the potential for clinical diagnosis and investigation of MG-related dry eye diseases like MG dysfunction (MGD) and acinar atrophy.

Objective Evaluation of Functionality of Filtering Bleb Based on Polarization-Sensitive Optical Coherence Tomography.

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.

Repeatability of corneal phase retardation measurements by polarization-sensitive optical coherence tomography.

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.

In Vivo and In Vitro Feasibility Studies of Intraocular Use of Polyethylene Glycol-Based Synthetic Sealant to Close Retinal Breaks in Porcine and Rabbit Eyes.

PURPOSE Absorbable polyethylene glycol-based synthetic sealant (PEG sealant) polymerizes under xenon illumination and forms a clear, flexible, and firmly adherent hydrogel. The intraocular biocompatibility of PEG sealant and efficacy for closing retinal breaks were evaluated. METHODS In an in vitro study, retinal detachment with a tear was created in porcine eyecups after vitreous gel removal. Polyethylene glycol-based synthetic sealant was applied to cover the tear and polymerized with a 40-second application of xenon light. Retinal adhesion strength was tested by forcefully squirting balanced salt solution (BSS) onto the retinal tear. Polyethylene glycol-based synthetic sealant was soaked in the BSS, incubated at 37°C, and the pH measured periodically over 72 hours. In an in vivo study, PEG sealant was injected into the vitreous cavity of the left eyes of rabbits. Ophthalmologic examinations were performed and bilateral ERGs were recorded simultaneously before and 28 days after injection. The eyes were enucleated for histological evaluation. RESULTS Adhesion of PEG sealant to the retina was good in BSS. A forceful squirt of BSS onto the retinal tear covered with PEG sealant did not detach the retina; the retinal tear without PEG sealant detached immediately. The pH of the BSS containing PEG sealant was between 7.2 and 8.2. No inflammatory reaction was observed in the eyes throughout 28 days of follow-up. The ERGs recorded before and after injection showed typical patterns. Histological examinations did not reveal any abnormality or inflammation. CONCLUSIONS Polyethylene glycol-based synthetic sealant appeared to effectively seal retinal breaks and was not toxic to the eye.

Quantitative Evaluation of Phase Retardation in Filtering Blebs Using Polarization-Sensitive Optical Coherence Tomography.

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.

Mesopic Functional Visual Acuity in Normal Subjects

To evaluate mesopic functional visual acuity (FVA) with a newly developed system in normal subjects and to compare the results with photopic FVA, sixty-eight healthy volunteers (24.03 ± 4.42 [mean ± standard deviation] years) were enrolled in this study. A commercially available FVA measurement system (AS-28; Kowa, Aichi, Japan) was modified to measure FVA under mesopic conditions as well as photopic conditions. Measurements were performed monocularly in photopic conditions during 60 seconds. After dark adaptation for 15 minutes, the same measurements were repeated in mesopic conditions. Outcomes included starting visual acuity (VA), FVA (the average of VAs), visual maintenance ratio (VMR), maximum VA, minimum VA, and numbers of blinks during the 60-second measurement session, and were compared between mesopic and photopic conditions. Starting VA was –0.11 ± 0.08 and 0.39 ± 0.12 logarithm of the minimum angle of resolution (logMAR) in photopic and mesopic conditions, respectively. FVA was –0.06 ± 0.09 and 0.52 ± 0.14 logMAR, VMR was 0.98 ± 0.02 and 0.94 ± 0.04, maximum VA was –0.15 ± 0.06 and 0.33 ± 0.12 logMAR, the minimum VA was 0.05 ± 0.12 and 0.78 ± 0.20 logMAR, and the number of blinks was 8.23 ± 7.54 and 7.23 ± 6.20, respectively. All these parameters except the number of blinks were significantly different between the two conditions (P < 0.001). Besides, the difference between maximum and minimum VAs and standard deviation of VA were significantly larger in mesopic than in photopic conditions (P < 0.001). This study revealed that not only overall visual function decline but also instability of vision under mesopic conditions even in healthy subjects.