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Dye-based angiography is the main imaging modality in evaluating the vasculature of the eye. Although most commonly used to assess retinal vasculature, it can also delineate normal and abnormal blood vessels in the anterior segment diseases-but is limited due to its invasive, time-consuming methods. Thus, anterior segment optical coherence tomography angiography (AS-OCTA) is a useful non-invasive modality capable of producing high-resolution images to evaluate the cornea and ocular surface vasculature. AS-OCTA has demonstrated the potential to detect and delineate blood vessels in the anterior segment with quality images comparable to dye-based angiography. AS-OCTA has a diverse range of applications for the cornea and ocular surface, such as objective assessment of corneal neovascularization and response to various treatments; diagnosis and evaluation of ocular surface squamous neoplasia; and evaluation of ocular surface disease including limbal stem cell deficiency and ischemia. Our review aims to summarize the new developments and clinical applications of AS-OCTA for the cornea and ocular surface.

BACKGROUND This case report illustrates the incidental detection of atypical hyporeflective bleb-like structures in an otherwise asymptomatic human cornea, highlighting the effectiveness of non-invasive biophotonic imaging techniques such as optical coherence tomography (OCT) and large-area confocal laser scanning microscopy (CLSM). CASE REPORT A 57-year-old man underwent a comprehensive ophthalmological examination, including slit-lamp biomicroscopy, corneal topography, and densitometry, as part of a clinical study. The patient presented with a clear cornea, a deep and optically empty anterior chamber, and a clear crystalline lens in both eyes. Best-corrected distance visual acuity was -0.1 logMAR. He denied ocular pain, tearing, or photophobia. There was no history of ocular trauma, infectious or genetic diseases, or ocular surgery. Further, OCT and large-area CLSM were employed for a more in-depth analysis of the corneal structure. Standard ophthalmological assessments indicated normal ocular health with no apparent corneal abnormalities. High-resolution OCT and large-area CLSM imaging revealed atypical hyporeflective bleb-like structures within the corneal epithelium and sub-basal nerve plexus but not in the stroma. CONCLUSIONS The authors hypothesize that the observed findings may indicate an early stage of epithelial basement membrane dystrophy, potentially preceding the manifestation of clinical symptoms, detectable solely through advanced biophotonic imaging methods. It is important to emphasize that these observations do not represent a definitive diagnosis. Nevertheless, the discovery of these atypical structures via advanced imaging underscores the importance of incorporating non-invasive biophotonic techniques into preoperative eye examinations in certain situations. This approach could significantly improve the early detection and management of corneal diseases, leading to improved patient outcomes.

Purpose: To determine the clinical outcomes in patients after type 1 Boston keratoprosthesis surgery and the significance of ultrasound biomicroscopy imaging for postoperative follow-up., Methods: This retrospective analysis included 20 eyes of 19 patients who underwent corneal transplantation with type 1 Boston keratoprosthesis between April 2014 and December 2021. Data on patient demographics, preoperative diagnosis, visual acuity, and postoperative clinical findings were analyzed., Results: Type 1 Boston keratoprosthesis implantation resulted in intermediate- and long-term positive outcomes. However, blindness and other serious complications such as glaucoma, retroprosthetic membrane formation, endophthalmitis, or retinal detachment also occurred. The use of ultrasound biomicroscopy imaging allowed for better evaluation of the back of the titanium plate, anterior segment structures, and the relationship of the prosthesis with surrounding tissues, which provided valuable postoperative information., Conclusion: Regular lifetime monitoring and treatment are necessary in patients who undergo Boston type 1 keratoprosthesis implantation for high-risk corneal transplantation. ultrasound biomicroscopy imaging can be a valuable imaging technique for the evaluation of patients with Boston type 1 keratoprosthesis, providing important information on anterior segment anatomy and potential complications. Further studies and consensus on postoperative follow-up protocols are required to optimize the management of patients with Boston type 1 keratoprosthesis.

Purpose: To report the clinical course and compare the utility of Scheimpflug tomography (ST) and anterior segment optical coherence tomography (AS-OCT) for central corneal thickness (CCT) and corneal densitometry (CD) assessment in patients with corneal crystals owing to nephropathic cystinosis., Methods: A retrospective chart analysis of three patients with nephropathic cystinosis and the presence of corneal cystine crystals in both eyes was performed. All patients underwent clinical examination and anterior segment photography, ST, and AS-OCT scans. Corneal densitometry was exported from built-in proprietary software for ST and from custom-made validated software for AS-OCT. Anterior segment optical coherence tomography images were rescaled to grayscale units from 0 (maximum transparency) to 100 (minimum transparency) to match built-in ST densitometry readings. Furthermore, the mean pixel intensity, representative of CD, was calculated from the pixels corresponding to the segmented cornea., Results: All three patients had pathognomonic cystine crystals deposits in the cornea and were treated with cysteamine medications that resulted in clinical improvement. The CCT measured using ST exhibited a range from 560 to 958 μm. Conversely, when assessed with AS-OCT, the CCT varied within the range of 548 to 610 μm. Both examinations could be performed, but in the more severe cases, AS-OCT showed far greater utility to estimate CD. In four of six eyes examined, ST showed disproportionate CCT values, compared with the AS-OCT, whereas reliable CD measurements were only available in AS-OCT., Conclusion: The AS-OCT could be considered a baseline ocular measurement in cystinosis and in the evaluation of disease progression and treatment efficacy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Aim: To investigate the corneal central and limbal thickness in cornea scar patients using high-resolution anterior segment optical coherence tomography (AS-OCT) and to determine the changes in the limbal region due to the corneal scar. Also, to evaluate tear film parameters in scar patients., Methods: Thirty patients with central corneal scar and 30 control subjects. The control subjects were healthy individuals who came to our clinic for routine ophthalmological examination. They were enrolled in this matched case-control study. Central epithelial thickness (ET), stromal thickness (ST), limbal epithelial thickness (LET), and limbal stromal thickness (LST) were analyzed using high-resolution AS-OCT. For evaluation of the ocular surface, the following techniques were used: tear break-up time (BUT) employing standard sterile strips of fluorescein sodium, Schirmer test-I (SCH), and the Ocular Surface Disease Index (OSDI) Questionnaire., Results: The mean central ET of the patient group was 51.5 ± 12.4 µm, while the mean central ET of the control group was 59.2 ± 9.0 µm. There was a statistically significant difference between patients and controls (p = 0.008). The mean LST of the patients was 747.9 ± 115.7 µm, and the mean LST of the controls was 726.3 ± 79.7 µm. There was a statistically significant difference between patients and controls according to BUT (p = 0.009) and SCH (p = 0.04). However, there was no significant difference between OSDI results of patients and controls (p = 0.08)., Conclusion: Corneal monitoring with high-resolution AS-OCT is a simple, noninvasive, useful technique for corneal scar patients. Cornea scars cause decreased ET. This result could be associated with lower tear film parameters in scar patients. The scar length is associated with higher intraocular pressure (IOP) values. Decreased LET and increased LST were detected in scar patients., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: To evaluate alterations in epithelial thickness during corneal degeneration, corneal pigmentation, and additional features observed through spectral-domain optical coherence tomography (SD-OCT) in brachycephalic dogs., Animals and Procedures: The study used 55 eyes from 49 brachycephalic dogs that underwent OCT-containing ophthalmic examinations. The examined eyes were classified into corneal degeneration, corneal pigmentation, and normal groups according to corneal lesions. For each eye, corneal epithelial thickness (CET) in the central cornea and maximum limbal epithelial thickness (maxLET) in 4 quadrants of limbus (superior, inferior, nasal, and temporal) were measured from OCT images. Additional abnormal findings on OCT images, including irregular epithelium, subepithelial hyperreflectivity, and conjunctivochalasis, were also recorded., Results: The corneal degeneration group had significantly thinner nasal and temporal maxLETs than that of the normal group (p < .001). In the central corneal OCT image of the corneal degeneration group, an irregular epithelium was observed in 70.6% and subepithelial hyperreflectivity in 82.4%, both of which were significantly higher than the normal group (p < .001). In a comparative analysis, the nasal, temporal, and inferior maxLETs were significantly thinner in the corneal pigmentation group than those in the normal group (p < .001, p < .001, and p = .01, respectively)., Conclusions: Morphological changes in the limbal epithelium were observed in dogs with corneal degeneration and corneal pigmentation. LET reduction could be associated with their pathogenesis and would be valuable as an additional parameter for corneal diseases., (© 2023 American College of Veterinary Ophthalmologists.)

Objective: To investigate the variance in corneal epithelial thickness (CET) and limbal epithelial thickness (LET) according to the age and skull type by using spectral-domain optical coherence tomography (SD-OCT) in normal dogs., Animals and Procedures: This study used an eye each from 46 dogs (24 brachycephalic and 22 non-brachycephalic dogs) assessed to have clear corneas. Each dog was classified according to age into groups 1 (0-5 years), 2 (6-10 years), and 3 (>11 years). OCT imaging was performed on the central cornea for CET and perpendicular to the quadrant of the limbus for LET. The average of the maximum LET (maxLET) value was measured in four eye quadrants., Results: Corneal epithelial thickness was not significantly different according to age in brachycephalic and non-brachycephalic dogs. Visualization of the limbal invagination was better when the maxLET was thick. Nasal and temporal maxLETs were significantly thicker than superior and inferior maxLETs in non-brachycephalic dogs. In brachycephalic dogs, there was a significant decrease in nasal maxLET with age (r s  = -0.489, p = .015). Significant differences between brachycephalic and non-brachycephalic dogs were observed in nasal maxLET (p = .024) and temporal maxLET (p = .011)., Conclusions: Invagination was better visualized in the nasal and temporal limbal quadrants of non-brachycephalic dogs compared with brachycephalic dogs, and the maxLETs of the regions were thicker than those of the brachycephalic dogs. CET and LET measurements using SD-OCT can help in clinical assessment and research on ocular surface diseases in dogs., (© 2022 American College of Veterinary Ophthalmologists.)

Objective: Detection of the Kayser-Fleischer (KF) ring in the diagnostic scoring and treatment follow-up of Wilson's Disease (WD) is important. Slit lamp (SL) biomicroscopic examination has traditionally been used in the evaluation of the KF ring. The role of Anterior Segment Optical Coherence Tomography (AS-OCT), which is used in various corneal diseases, in the detection of KF rings has attracted attention in recent years. In our study, we tried to demonstrate the effectiveness of AS-OCT in detecting the KF ring by comparing it with SL biomicroscopic examination., Patients and Methods: 64 of 356 patients followed in our outpatient clinic due to WD were included in the study in the order of their admission to the outpatient clinic. The KF ring was evaluated in both eyes by SL-biomicroscopic examination and AS-OCT. Ophthalmic examination, and findings were performed by the same physician., Results: Age range was 18-67 years, mean 33.06±10.83 years, gender was 39.1% (n: 25) female. At the time of diagnosis, the mean age was 19.48 ± 9.36 years, range was minimum 5 years and maximum 51 years. Clinical presentation was mixed type involvement n: 18 (28.1%), hepatic involvement n: 32 (50%), neurological involvement n: 14 (21.9%). The follow-up period was 2-257 months (74.6±76.16). The presence of KF ring was evaluated together with both AS-OCT and slit-lamp examination, the presence of KF could be detected in both AS-OCT and SL biomicroscopic examination in 10 patients (15.6%), in 12 (18.8%) of the cases KF ring is positive in AS-OCT but was negative in Slit-lamp biomicroscopic examination, in 65.6 (n: 42) of the cases OCT and slit-lamp biomicroscopic examination results were negative., Conclusions: The sensitivity of AS-OCT in detecting the KF ring was higher than the slit-lamp biomicroscopic examination. AS-OCT can detect early stage of KF rings in Wilson's Disease patients, so that diagnosis and treatment accuracy can be evaluated effectively.

Objective: To propose a deep-learning network for the diagnosis of two corneal diseases: Fuchs' endothlelial dystrophy and keratoconus, based on optical coherence tomography (OCT) images of the cornea., Methods: In this paper, we propose a novel network with parallel resolution-specific encoders and composite classification features to directly diagnose Fuchs' endothelial dystrophy and keratoconus using OCT images. Our proposed network consists of a multi-resolution input, multiple parallel encoders, and a composite of convolutional and dense features for classification. The purpose of using parallel resolution-specific encoders is to perform multi-resolution feature fusion. Also, using composite classification features enhances the dense feature learning. We implemented other related networks for comparison with our network and performed k-fold cross-validation on a dataset of 16,721 OCT images. We used saliency maps and sensitivity analysis to visualize our proposed network., Results: The proposed network outperformed other networks with an image classification accuracy of 0.91 and a scan classification accuracy of 0.94. The visualizations show that our network learned better features than other networks., Significance: The proposed methods can potentially be a step towards the early diagnosis of corneal diseases, which is necessary to prevent their progression, hence, prevent loss of vision.

Abstract: Intraoperative optical coherence tomography (OCT) has the potential to revolutionize lamellar corneal surgery and facilitate many other types of ocular surgery because it readily visualizes ocular structures that can be difficult to discern with a coaxial microscope, particularly through a cloudy cornea. Systems that can provide a high-quality image on demand in the surgeon's oculars, rather than just on an adjacent monitor, are the most useful because they allow the surgeon to rely on the OCT image while operating, without having to look away from the surgical field. Useful applications in lamellar corneal surgery include assessing graft attachment with Descemet stripping endothelial keratoplasty and discerning graft orientation with Descemet membrane endothelial keratoplasty, which otherwise could be challenging in an eye with a cloudy cornea. Intraoperative OCT is particularly helpful when performing deep anterior lamellar keratoplasty in cases in which a big bubble should not be attempted or cannot be achieved because it enables better intraoperative control of the incision depth and allows the surgeon to assess the uniformity of the dissection plane to optimize visual outcomes. Intraoperative OCT is also useful when judging the depth of a scar for a lamellar dissection, when evaluating intraocular lens positioning in the capsular bag, or when locating and removing retained nuclear fragments from an eye with a poor view because of a cloudy cornea. The primary barrier to the adoption of this valuable technology is cost., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Significance: Ocular surface squamous neoplasias are superficial tumors of the cornea and conjunctiva that can be sight threatening if neglected. Therefore, accurate noninvasive diagnostic modalities are needed., Purpose: The purpose of this case series was to describe the hallmark features of ocular surface squamous neoplasia on high-resolution optical coherence tomography (HR-OCT) imaging and its use in the evaluation and management of superficial ocular tumors., Case Series: Five eyes of four patients with ocular surface squamous neoplasia are described. Whereas two eyes displayed the classic clinical features of ocular surface squamous neoplasia, three of the five eyes had more subtle atypical features. However, all shared features on HR-OCT of epithelial thickening and hyperreflectivity with abrupt transitions between normal and abnormal tissue, classic features of ocular surface squamous neoplasia. All lesions ultimately underwent incisional or excisional biopsy and were confirmed to be ocular surface squamous neoplasia on histopathology., Conclusions: Ocular surface squamous neoplasia may present as a classic tumor but can also have subtle features or masquerade. Accurate methods to diagnose and manage patients with ocular surface squamous neoplasia are necessary. With recent advancements in technology, HR-OCT has been demonstrated to accurately identify ocular surface squamous neoplasia with the repeatable optical findings of (1) epithelial thickening, (2) epithelial hyperreflectivity, and (3) abrupt transition zone between normal and abnormal tissue. This case series demonstrates how HR-OCT can help provide an optical biopsy to guide appropriate diagnosis and management of this neoplastic lesion., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

Purpose: To describe the morphological patterns of keratic precipitates (KPs) in vitreoretinal lymphoma (VRL) using in vivo confocal microscopy (IVCM)., Methods: Six eyes of three biopsy-proven VRL patients were included. KPs were identified and analyzed on IVCM., Results: On examination, pigmented KPs in four eyes, white central KPs in two eyes and anterior chamber cells with flare in six eyes and pseudo hypopyon in one eye were identified. A typical floral pattern of KPs on IVCM was noted in all eyes. Three eyes each showed the complete and incomplete floral patterns, respectively. Resolution of KPs on IVCM was noted after chemotherapy., Conclusion: In addition to the routinely used clinical and imaging markers like the visual acuity, presence of lymphomatous cells in the vitreous and optical coherence tomography findings, the presence and appearance of KPs on IVCM can also be considered as a useful, diagnostic and treatment monitoring marker in VRL.

Purpose: To determine the utility of anterior segment optical coherence tomography angiography (AS-OCTA) in assessing limbal stem cell deficiency (LSCD)., Methods: Twenty-six eyes of 24 LSCD patients, classified clinically into stage I, II and III, and 12 eyes of 12 healthy subjects were included. AS-OCTA images were analyzed by two masked observers, measuring the maximum corneal vascular extension (CoVE) from the limbus to the furthest vessel over the cornea, and corneal vascular thickness (CoVT) from the most superficial to the deepest corneal vessel., Results: CoVE was 0.27 ± 0.10, 0.79 ± 0.21, 1.68 ± 0.89 and 2.53 ± 0.82 mm in controls, stage I, II and III LSCD, respectively (p < 0.001). The CoVT was 51.0 ± 19.4, 113.7 ± 36.6, 129.7 ± 39.3 and 336.0 ± 85.0 μm, respectively (p < 0.001). There was a significant difference in CoVE and CoVT between all stages compared to controls, and between stage I and III LSCD (p < 0.001). Further, CoVE showed a significant difference between stage I and II, whereas CoVT showed a significant difference between stage II and III LSCD (p < 0.001). BCVA showed strong correlation with CoVT (r = 0.765, p < 0.001) and moderate correlation with CoVE (r = 0.547, p = 0.001). AS-OCTA parameters showed excellent intra- and inter-class correlation coefficients (>0.900)., Conclusion: LSCD demonstrates significant changes in CoVE and CoVT as early as stage I LSCD in comparison to controls. CoVE and CoVT strongly correlate to both disease severity and BCVA. AS-OCTA may provide novel quantitative and non-invasive parameters to assess LSCD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: 1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma., Methods: A thorough literature search was conducted on databases for studies published in English regarding the available methods to determine the role of collecting channels in normal and glaucomatous patients and to assess their patency., Results: Intraocular pressure (IOP) exists as a balance between aqueous humor production and aqueous humor outflow. Collector channels are an essential anatomical constituent of the distal portion of the conventional aqueous humor outflow pathway. There are different surgical options for glaucoma management and with the recent advances in Schlemm's canal-based surgeries, collector channel's patency became a key factor in determining the optimum management for the glaucomatous eye. The advent of anatomic imaging methods has improved the ability to visualize collector channel morphology in-vitro, including swept-source optical coherence tomography (SS-OCT), spectral domain optical coherence tomography (SD-OCT), micro-computed tomography (micro CT), new immunohistochemistry techniques and scanning electron microscopy. The recent advent of real-time assessment of collector channel patency (including evaluation of episcleral venous outflow, observation of episcleral venous fluid wave, and tracer studies utilizing fluorescein, indocyanine green, and trypan blue) has been validated by the aforementioned anatomic imaging modalities., Conclusions: New modalities of in-vitro and in-vivo studies of collector channels provide promise to aid in the assessment of collector channel patency and individualization of surgical management for glaucoma patients.

Aims: The goal was to find if changes in Fabry keratopathy were clinically observable over time. Also observed were variations of Fabry keratopathy, supplemental features, unique presentations and differences between keratopathies of right and left corneas and the same family and genotype., Methods: Biomicroscopic images of Fabry keratopathy in 10 persons with classic Fabry disease, 5 men and 5 women, were captured over an 18-month period. The keratopathies were categorised and scrutinised for changes over time, and differences between corneas of the same individual, family and genotype., Results: Fabry keratopathy ranged from mild change to marked change over 18 months. There was a great variety of whorl patterns. A few keratopathies were amorphous without vortices and many vortices were supplemented with amorphous features. All keratopathies were accompanied by diffuse epithelial haze. There was a range from negligible difference to marked difference between right and left eyes of the same individuals with similarities appearing as imprecise mirror images of each other. In some corneas, prominent vertical streams from the superior limbus integrated into the primary keratopathy. Comparisons between persons with the same family and genotype were obscured by gender and differences between right and left eyes., Conclusions: Practitioners should be better able to detect Fabry disease having a fuller understanding of the variety of presentations of the dynamic, pathognomonic Fabry keratopathy. Routes of continuous centripetal renewal of corneal epithelium are spatially unique to each eye, in some cases subsidised by direct contribution of basal cells streamed from the superior limbus., Competing Interests: Competing interests: MDS was an Associate Professor at the University of Alabama at Birmingham and is currently in clinical practice at Holcomb Laser Center in Cullman, Alabama. She is an optometric member of the National Academies of Practice. WJB is a Professor Emeritus of the University of Alabama at Birmingham and President of Material Performance Assessments, LLC., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We aimed to compare the morphological characteristics of corneal endothelial cells in type 2 diabetic patients and age-matched healthy subjects by specular microscopy. We also aimed to determine the association of corneal morphological features with the general characteristics and laboratory data of diabetic patients, including disease duration, haemoglobin A1c (HbA1c) levels and urine albumin creatinine ratio., Methods: A total of 195 diabetic patients and 100 healthy controls were enrolled in the study. All participants underwent a complete ophthalmological examination. Corneal endothelial measurements were performed using a noncontact specular microscopy. Laboratory data including serum fasting glucose, haemoglobin A1c levels, creatinine levels, and the urinary albumin-to-creatinine ratio were recorded. Diabetic patients were further subdivided into 3 groups according to the presence and stage of diabetic retinopathy. Specular microscopy findings and central corneal thickness of all patients were compared., Results: The ECD and hexagonal cell ratio were significantly lower, while the average cell size, CV%, and central corneal thickness were determined to be significantly higher in diabetic patients than in healthy controls (p = 0.001). With the presence and advancement of diabetic retinopathy, the ECD and hexagonal cell ratio decreased, while the average cell size, CV%, and central corneal thickness increased. When correlation analysis was performed between corneal morphological features and laboratory data of diabetic patients, ECD showed a significant negative correlation with diabetes duration (p = 0.028). HbA1c levels, urinary albumin-creatinine ratio (p = 0.041), average cell size and CV showed a positive correlation with these parameters., Conclusion: In conclusion, keratopathy is an important complication of type 2 diabetes. With an increase in the stage of diabetic retinopathy, alterations in corneal findings also increased. In that respect, we can suggest that keratopathy should be evaluated more cautiously in diabetic patients.

Objective: To assess if anterior segment optical coherence tomography (AS-OCT) is a noninvasive diagnostic method suitable to differentiate benign corneo-conjunctival lesions (pterygium) from premalignant lesions (corneo-conjunctival intraepithelial neoplasia, CIN)., Material and Methods: An observational, analytical and cross-sectional study was conducted in 22 eyes with conjunctival lesions clinically suspicious for pterygium and CIN during two years. Morphological differences between both lesions were studied with AS-OCT; epithelial thicknesses (EE) and extension length on corneal surface (GIC) were compared between both groups. A surgical excision of the lesion was performed for histopathological diagnosis., Results: Mean age of patients with pterygium (n=18) was 52.67±15 y.o and 74±12 y.o in subjects with CIN (n=4) (p<0.021). In pterygia, AS-OCT showed typical features (normal, thinning or slightly thickened EE; 77.4±26μm), in addition to an increase in wedge-shaped subepithelial tissue. Patients with CIN had a mean thickened EE (262.5±124μm) and strongly hyperreflective, with abrupt transition between normal and pathological epithelium. Analysis of EE between subjects with pterygium and CIN revealed statistically significant differences (p<0.002). ROC curve revealed a 100% sensitivity and specificity of OCT-SA in differentiation between CIN and pterygium, using 141μm as cutoff point of EE., Conclusion: AS-OCT is a useful tool for the differentiation between pterygium and CIN able to provide typical morphological characteristics. An EE greater than 141μm in AS-OCT suggests a sensitivity and specificity of 100% for the diagnosis of CIN., (Copyright © 2020 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Presence of corneal cystine crystals is the main ocular manifestation of cystinosis, although controversial findings concerning the corneal layer with the highest density have been reported. The aim of this study was the analysis of the characteristics of crystal arrangement in different corneal layers and the assessment of corneal morphological changes with age., Methods: A cross sectional study was carried out in three children and three adults who had nephropathic cystinosis and corneal cystine depositions. All patients underwent a comprehensive ophthalmological examination including best corrected distance visual acuity, slit-lamp examination, in vivo confocal microscopy and anterior segment optical coherence tomography. An evaluation of the depth of crystal deposits and crystal density in different corneal layers was also performed. Due to the low number of subjects no statistical comparison was performed., Results: Anterior segment optical coherence tomography images revealed deposition of hyperreflective crystals from limbus to limbus in each patient. Crystals appeared as randomly oriented hyperreflective, elongated structures on in vivo confocal microscopy images in all corneal layers except the endothelium. In children the deposits occurred predominantly in the anterior stroma, while in adults, the crystals were mostly localized in the posterior corneal stroma with the depth of crystal deposition showing an increasing tendency with age (mean depth of crystal density was 353.17 ± 49.23 μm in children and it was 555.75 ± 25.27 μm in adults). Mean crystal density of the epithelium was 1.47 ± 1.17 (median: 1.5; interquartile range: 0.3-2.4). Mean crystal density of the anterior and posterior stroma of children and adults was 3.37 ± 0.34 (median: 3.4; interquartile range: 3.25-3.55) vs. 1.23 ± 0.23 (median: 1.2; interquartile range: 1.05-1.35) and 0.76 ± 0.49 (median: 0.7; interquartile range: 0.4-1.15) vs. 3.63 ± 0.29 (median: 3.7; interquartile range: 3.45-3.8), respectively. Endothelium had intact structure in all cases. Some hexagonal crystals were observed in two subjects., Conclusions: In vivo confocal microscopy and anterior segment optical coherence tomography confirmed an age-related pattern of crystal deposition. In children, crystals tend to locate anteriorly, while in adults, deposits are found posteriorly in corneal stroma.

Background: To develop a method, using current clinical instrumentation, to estimate the Young's modulus of the human cornea in vivo., Methods: Central corneal curvature (CCC), central corneal thickness(CCT), intraocular pressure (IOP) was measured with the Goldmann tonometer (IOPG) and the Pascal Dynamic Corneal Tonometer(PDCT) in one eye of 100 normal young human subjects (21.07 ± 2.94 years) in vivo. The Orssengo and Pye algorithm was used to calculate the Young's modulus of the corneas of these subjects., Results: The Young's modulus(E) of the corneas of the subjects using the PDCT and IOPG results (Ecalc) was 0.25 ± 0.10MPa, and without the PDCT results (Eiopg) was 0.29 ± 0.06MPa. The difference in these results is due to the difference in tonometry results between the two instruments, as the mean PDCT result for the subjects was 16.89 ± 2.49mmHg and the IOPG result 15.06 ± 2.71mmHg. E was affected by the CCC of the subjects but more particularly by the CCT and IOP measurements. Corneal stiffness results are also presented., Conclusion: Two methods have been developed to estimate the Young's modulus of the human cornea in vivo using current clinical instrumentation. One method (Ecalc) is applicable to the general corneal condition, and Eiopg to the normal cornea, and these results can be used to calculate corneal stiffness., Competing Interests: The authors have declared that no competing interests exist.

A 3-month-old baby presented with a whitish lesion over the right cornea since birth. Due to the clinical and ultrasonic characteristics of the lesion, a manual anterior lamellar keratoplasty was performed. Histopathological examination showed it to be a simple grade II epibulbar choristoma. Although dermoid tumours are usually considered as benign, some of them, depending on their location, can seriously affect the vision of a paediatric patient. Due to the high probability of amblyopia in these cases, a surgical procedure is mandatory. Anterior lamellar keratoplasty is recommended when the visual axis is compromised without intraocular implications., (Copyright © 2019. Publicado por Elsevier España, S.L.U.)

Fibrous histiocytoma (FH) commonly occurs in the superficial layers of the skin. Orbit and limbus are documented ophthalmic sites of involvement but isolated corneal FH has never been reported in literature. We present the first case of FH exclusively involving the cornea where a 10-year-old male child presented with a 3-month history of a painless growth on the superior cornea of the right eye with deterioration of vision. Tumor excision with therapeutic penetrating keratoplasty was done and the histopathological examination confirmed the diagnosis. There was no recurrence and the corneal graft was clear at 1 year., Competing Interests: None

Competing Interests: There are no conflicts of interest.

Purpose: To evaluate, through the in vivo confocal microscopy, the pathological changes of each corneal layer in eyes affected by pseudoexfoliation syndrome., Methods: We studied 40 eyes of 40 patients with diagnosis of unilateral senile cataract associated with pseudoexfoliation syndrome and 40 eyes of 40 control subjects with senile cataract without pseudoexfoliation syndrome. All patients underwent a complete ophthalmic examination including best corrected visual acuity, slit-lamp examination, corneal sensitivity measurement using a Cochet-Bonnet nylon thread esthesiometer, and anterior segment optical coherence tomography (Visante OCT, Carl Zeiss Meditec AG, Germany); in vivo confocal microscopy of corneal sections (endothelium, stroma, sub-basal nerve plexus, and superficial and basal epithelium) was performed with the ConfoScan 4.0 (Nidek, Japan)., Results: In pseudoexfoliation syndrome group, the mean corneal sensitivity was 44.1 ± 1.3 mm and in the control group was 55.6 ± 4.7 mm. The corneas of the eyes with pseudoexfoliation syndrome were significantly less sensitive than those of control group eyes (p < 0.001). Pseudoexfoliation syndrome eyes had a lower nerve density and less nerve beadings and a higher degree of tortuosity in sub-basal plexus compared to the control group. The cell density of epithelial and endothelial layers was significantly lower in pseudoexfoliation syndrome eyes than controls. In 80% of pseudoexfoliation syndrome eyes, we found activated keratocytes and inflammatory cells in the anterior stroma., Conclusion: Our study demonstrates the morpho-structural corneal alterations in eyes affected by pseudoexfoliation syndrome, using corneal in vivo confocal microscopy as a non-invasive and high-reproducible technique to evaluate pathophysiology of each corneal layer; the sub-basal nerve plexus alterations are correlated with the lower corneal sensitivity.

Simple limbal epithelial transplantation (SLET) is an emerging technique for treating unilateral limbal stem cell deficiency. We report the high-resolution, anterior segment optical coherence tomography (OCT) features of the first 2 weeks of a patient undergoing SLET for an old acid injury of the right eye, repeatedly from postoperative day 1 through day 14. Three out of 11 explants with the subjacent human amniotic membrane (hAM) and the overlaid bandage contact lens were imaged. The hAM was intact and of the same thickness throughout the study period; the sub-hAM space increased from day 3 to 9 and disappeared by day 10; the explants started thinning from day 3 with the fibrin around them starting to decrease from day 2 and completely disappeared by day 4. Epithelialization occurred between day 8 and 14 and proceeded more rapidly towards the limbus than centrally. There was no change of the corneal stromal thickness or reflectivity. This case report uses high-definition, spectral-domain OCT to document the events on the ocular surface after a successful SLET surgery and opens up an avenue to study epithelialization in a convenient and noninvasive manner., Competing Interests: There are no conflicts of interest

Purpose : To characterize and correlate guttata severity, Descemet's membrane thickness (DMT), central cornea thickness (CCT) in corneas with guttae using specular microscopy and spectral-domain optical coherence tomography (SD-OCT) and test the Doheny Image Reading Center (DIRC) specular microscopy-based corneal guttata severity scale. Methods : Forty-nine eyes of 49 patients with guttata and 36 eyes of age-matched of 36 normal controls were enrolled in the study. Three images of the central cornea and four of the peripheral cornea (inferior, superior, nasal and temporal) of each eye were taken using the Konan NSP-9900 specular microscope. A volume scan of the central cornea cross-section was collected on each eye using the Heidelberg Spectralis SD-OCT. The density of endothelial guttata based on specular images was graded on a 0-4 scale, and the Descemet's membrane thickness (DMT) and central corneal thickness (CCT) were manually measured by two trained graders. Results : The DIRC corneal guttata severity scale showed good reproducibility of all corneal endothelial images (weighted Kappa = 0.87). Mean DMT was 16.1 ± 2.4 µm in controls and 25.5 ± 10.9 µm in corneas with guttata ( P < 0.001). Mean CCT was 552 ± 26 µm in controls and 603 ± 55 µm in corneas with guttata ( P < 0.001). Guttata severity was significantly correlated with both DMT (r = 0.743, P < 0.001) and CCT (r = 0.569, P < 0.001). Age was moderately correlated with DMT (r = 0.472, P = 0.003) and mildly correlated with guttata severity (r = 0.285, P = 0.031), but was not correlated with CCT (r = 0.058, P = 0.681). Guttatta grade 3 corneas displayed an increase in DMT and guttata grade 4 was associated with a significant increase in CCT. Conclusions : The DMT and CCT are increased in corneas with guttata. The higher density of guttae is correlated with increased thickness. Specular microscopy combined with SD-OCT can be used as a good approach to assess the severity of FECD.

Rationale: Lipid deposition on the cornea without previous infection, inflammation, vascularization, or trauma is idiopathic lipid keratopathy. In vivo laser confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) are 2 noninvasive methods that can help identify the structures and morphological characteristics of the focus., Patient Concerns: A 63-year-old woman with ipsilateral corneal lipid deposits developing from a small white spot into a yellow-white superotemporal elliptic shape within a year. AS-OCT showed peripheral deep stromal deposits. IVCM showed hyper-reflective material with typical crystalline-like or needle-like structures in the superotemporal area., Diagnosis: Idiopathic lipid degeneration., Interventions: Topical steroids eye drops 3 times a day for a month and further consultation every 3 months., Outcomes: This patient of idiopathic lipid keratopathy was observed every 3 months and till now we have reviewed this patient twice. Topical steroids eye drops were only used during the first month. No further development was observed about the lesion and the patient's visual acuity remained good., Conclusion: IVCM and AS-OCT can help identify the characteristic crystalline-like or needle-like hyper-reflective material that could help diagnosis of idiopathic lipid degeneration.

Purpose: The purpose of this study was to investigate the use of anterior segment imaging in diagnosing Kayser-Fleischer rings in patients with Wilson disease., Methods: In a tertiary center for Wilson disease, patients were examined with a Pentacam HR Scheimpflug-based tomography device in addition to conventional slit-lamp examination. The inferior part of the cornea was analyzed using both a built-in densitometry module and ImageJ., Results: Thirty-one patients with Wilson disease (78% of all Danish patients) were included, resulting in 83 examinations over a 5-year period. Ten had a manifest Kayser-Fleischer ring in the inferior part of the cornea on at least 1 examination, 5 had other causes of peripheral corneal scatter, and 16 had normal examinations. The built-in densitometry module performed poorly in discriminating between the presence and absence of a Kayser-Fleischer ring. However, analysis of the images in ImageJ and calculation of a normalized signal (peak posterior value/peak anterior value) with a cutoff value set to 1 detected 28 of 31 Kayser-Fleischer rings and resulted in 96% sensitivity and 95% specificity. In 12 patients who underwent 3 or more examinations during the period, changes in the normalized signal seemed to reflect the efficiency of the treatment, although more studies are needed for this conclusion., Conclusions: ImageJ-based analysis of Pentacam images has a high sensitivity in detecting Kayser-Fleischer rings and can be used as a diagnostic procedure for Wilson disease and may be a tool to monitor the disease in an objective manner.

Purpose: To determine whether the corneal topographic parameter values, individual corneal layer thicknesses, and its endothelial layer morphology are different in patients with hemifacial spasm (HFS) than in the control contralateral eye., Methods: This study was designed as a prospective study. Among patients who applied to our hospital within the past 3-year period, those with HFS in one eye (study eyes) and a completely normal contralateral eye (control eyes) were included in this study. In addition to a complete ophthalmologic examination, all patients were scanned by the Pentacam Scheimpflug camera, and a corneal endothelium cell count was taken using a Topcon Specular Microscope. Also, the thickness of the corneal sublayers was measured on the central cornea with anterior segment module of spectral domain optical coherence tomography. Data entered using SPSS software were then evaluated by paired t test; P<0.05 value was considered statistically significant., Results: Twenty-eight patients (16 women and 12 men) were evaluated. Steep K, Kmax, and astigmatism values were significantly higher in the study eyes of patients with HFS than in the control eyes (P<0.05, for all). In addition, the total corneal thickness and corneal stromal thickness measurements in the study eyes were statistically significantly thinner than the control eyes (P=0.04 and P<0.001, respectively). Specular microscopy parameters were not statistically significant between the study eyes and control eyes (P>0.05, for all)., Conclusion: Corneal stromal thinning suggests that chronic exposure to hypoxia may induce this effect through extracellular matrix remodeling and losses in collagen framework content in patients with HFS.

Neurotrophic keratopathy (NK) is a rare degenerative corneal disorder characterized by instability of epithelial integrity with consequent epithelial defects that can worsen up to persistent epithelial defects with stromal melting and ulceration. The pathogenesis of NK springs from a variable degree of damage to the trigeminal nerve plexus, leading to a reduction or total loss of corneal sensitivity. Mackie classification (1995) distinguishes three stages of NK, based on the severity of clinical presentation. The technological innovations in corneal diagnostic imaging allow clinicians to accurately study the morphometry and morphology of corneal structure with microscopic resolution. In this study, 45 patients affected by NK at different stages underwent in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) with particular attention to analyze subbasal nerve plexus fibers and the stromal structure. At the light of IVCM and AS-OCT observations, we propose a different staging of NK with respect to the Mackie's classification that takes into account the severity of subbasal nerve fibers damage and the extension in depth of stromal ulceration; this classification better defines, at the time of diagnosis, the cellular and structural alterations in the affected corneas, with possible prognostic and therapeutic values in the management of NK., (© 2018 Wiley Periodicals, Inc.)

Wilson's disease is an autosomal recessive hereditary metabolic disease with a pathological accumulation of copper in tissues. This study presents the case of a family, where two females and one male from among six siblings had this disease. While in the case of the two women only the liver was affected, the young man presented with both psychiatric and ophthalmic disorders. Modern examination methods (anterior segment optical coherence tomography, corneal topography, endothelial specular microscopy) were used to gather data on the corneal disorder that manifested with the classic Kayser-Fleischer ring. We underline the importance of ophthalmological checkup which may help to diagnose this disease. Orv Hetil. 2019; 160(14): 555-557.

To identify the microstructural modification of the corneal layers during the course of the disease, optical technologies have been pushing the boundary of innovation to achieve cellular resolution of deep layers of the cornea. Gabor-domain optical coherence microscopy (GD-OCM), an optical coherence tomography-based technique that can achieve an isotropic of ∼2-μm resolution over a volume of 1  mm  ×  1  mm  ×  1.2  mm, was developed to investigate the microstructural modifications of corneal layers in four common corneal diseases. Since individual layer visualization without cutting through several layers is challenging due to corneal curvature, a flattening algorithm was developed to remove the global curvature of the endothelial layer and display the full view of the endothelium and Descemet's membrane in single en face images. As a result, GD-OCM revealed the qualitative changes in size and reflectivity of keratocytes in Fuchs endothelial corneal dystrophy (FECD), which varied by the degree of disease. More importantly, elongated shape and hyperactivation characteristics of keratocytes, associated with the early development of guttae, appeared to start in the posterior stroma very early in the disease process and move toward the anterior stroma during disease progression. This work opens a venue into the pathogenesis of FECD.

We report a case of an Angiostrongylus parasite in the corneal stroma in an 8-year-old boy and our technique for its removal. The parasite was identified on slit-lamp examination. Its location was confirmed on anterior segment optical coherence topography (AS-OCT). The parasite was found on the superficial corneal stroma in the periphery and was removed after lamellar dissection of the cornea following marking with trephine., (Copyright © 2019 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background/aims: Limbal stem cell deficiency (LSCD) is characterised by a marked decrease in limbal stem cells. It is classified primarily using subjective slit-lamp observations. In vivo confocal microscopy (IVCM) can non-invasively provide objective information on the condition of the limbal niche, the corneal epithelial basal cell density and the corneal sub-basal nerve plexus density (SND). We here used IVCM to evaluate changes in SND to improve LSCD classification., Methods: We evaluated and classified 38 patients (76 eyes, 44 with LSC and 32 control eyes) using the Rama, López-García and Deng (clinical and confocal) classifications and evaluated the concordance of the confocal and clinical classifications. We constructed a logistic regression model using multivariate analysis to correlate different degrees of conjunctivalisation with IVCM parameters and used receiver operating characteristic (ROC) curve analysis to establish the SND cut-off value with maximum diagnostic sensitivity and specificity., Results: The classification systems correlated moderately at best (kappa, 0.449). The corneal SND of cases (6469±6295 µm/mm 2 ) was less (p<0.001) than in controls (20911±4142 µm/mm 2 ). The SND, but not basal cell density, played a protective role against conjunctivalisation (OR, 0.069; 95% CI 0.008-0.619; p=0.01). An SND cut-off value of 17 215 µm/mm 2 yielded a sensitivity and specificity of 95.5% and 90.6%, respectively, for LSCD diagnosis., Conclusion: The density of the corneal sub-basal nerve plexus was inversely related to conjunctivalisation in LSCD. Further studies are needed to verify this and to elucidate the directionality between these factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study analyzes images of Kayser-Fleischer (K-F) rings in patients with Wilson disease (WD) using in vivo confocal microscopy (IVCM) and explores whether IVCM can be a useful clinical tool in facilitating the diagnosis and characterization of K-F rings., Methods: One hundred four eyes of 52 patients with WD and K-F rings (K-F group) and 52 normal eyes of 52 age- and gender-matched control subjects (control group) were enrolled in the study. Both K-F and control groups consisted of 29 male patients and 23 female patients. IVCM imaging was performed, and images of the peripheral Descemet membrane were analyzed., Results: All patients in K-F group showed abnormal patterns in the peripheral Descemet membrane from IVCM images. These abnormalities can be generally divided into 3 types: patchy, stripy, and spotty patterns. Each patient may have a combination of these patterns, with patchy pattern being most prevalent (100%), whereas stripy and spotty patterns are present in 30% to 40% of the K-F rings. Notably, these patterns are not correlated with other systematic symptoms of WD., Conclusions: IVCM images can be used as an objective clinical diagnostic tool to facilitate the identification of K-F rings and the diagnosis of WD.

Importance: Although the most recent American Joint Committee on cancer staging guidelines for ocular surface squamous neoplasia place a heightened emphasis on biopsy and histopathologic analysis, the interpretation and clinical relevance of these staging criteria are not always clear. We address limitations of using histopathologic analysis to predict clinical outcomes and suggest less-invasive assessments., Background: To investigate the impact of histopathologic depth of invasion on outcomes for tumours with the common presentation of multiple structure involvement., Design: Retrospective chart review at tertiary institution., Samples: Of 41 eyes with ocular surface squamous neoplasia between 2012 and 2017, 27 tumours involving multiple ocular structures clinically were included., Methods: Biopsied tumours were determined to be invasive beyond the basement membrane or non-invasive; non-biopsied tumours were clinically identified with unknown depth of invasion. Outcomes were compared using Fisher's exact or Student's t tests., Main Outcome Measures: Proportion of tumours cured, recurred and/or persisting., Results: Twelve tumours (44%) received primary excisional biopsy, 10 (37%) received chemotherapy without biopsy and 5 (19%) received chemotherapy and biopsy. Clinical diagnosis was correct in all biopsied cases. While there were no significant differences in outcomes between invasive vs non-invasive tumours or treatments, there was a trend toward larger basal diameter in recurrent tumours regardless of treatment., Conclusions and Relevance: When ocular surface squamous neoplasia tumours with similar clinical involvement were compared, histopathologic depth of invasion was not predictive of clinical outcomes. Future staging criteria may consider the potential of largest basal dimension for more accurate prognostication., (© 2018 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To describe prescriber reported scleral lens fitting and assessment strategies., Methods: The SCOPE (Scleral Lenses in Current Ophthalmic Practice Evaluation) study group designed and administered an IRB approved, electronic survey (REDCap) regarding current scleral lens fitting and assessment methods. The survey was distributed to attendees of the 2017 Global Specialty Lens Symposium., Results: 95 practitioners responded to the survey. Over half of the respondents, 58% (55/95) reported fitting scleral lenses for less than five years (new prescribers), and 42% (40/95) reported fitting scleral lenses for more than five years (experienced prescribers). There was a statistically significant difference between their initial use of technology (χ 2  = 21.117, p < 0.0005) in selection of a diagnostic lens. New prescribers consider base curve first (60%, 33/55), while experienced prescribers considered sagittal depth first (63%, 25/40) in their initial scleral lens selection. All of the experienced lens prescribers (100%, 39/39) reported estimating central clearance by comparing thickness of the post-lens tear reservoir to scleral lens thickness using a slit lamp beam at least some of the time, and 62% of new scleral lens prescribers (34/55; χ 2  = 19.175, p < 0.0005) reported doing so. All (100%, 40/40) experienced prescribers schedule scleral lens follow-ups at a specific time and assess conjunctival compression (100%, 40/40), conjunctival staining (100%, 39/39), and corneal staining (100%,40/40) after lens removal., Conclusions: Practitioners with varying backgrounds and experience have added sclerals to their lens inventories. However, definite guidelines for fitting have not been developed. The results of a survey are provided; demonstrating that among practitioners with greater than 5 years of scleral lens experience, a consensus has emerged for best practices. Strategies for lens evaluation, which may inform future efforts at generating scleral fitting standards are described., (Copyright © 2018 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess depth-dependent corneal displacements in live normal subjects using optical coherence elastography (OCE)., Methods: A corneal elastography method based on swept-source optical coherence tomography (OCT) was implemented in a clinical prototype. Low amplitude corneal deformation was produced during OCT imaging with a linear actuator-driven lens coupled to force transducers. A cross-correlation algorithm was applied to track frame-by-frame speckle displacement across horizontal meridian scans. Intra-measurement force and displacement data series were plotted against each other to produce local axial stiffness approximations, k, defined by the slope of a linear fit to the force/displacement data (ignoring non-axial contributions from corneal bending). Elastographic maps displaying local k values across the cornea were generated, and the ratio of mean axial stiffness approximations for adjacent anterior and posterior stromal regions, ka/kp, was calculated. Intraclass correlation coefficients (ICC) were used to estimate repeatability., Results: Seventeen eyes (ten subjects) were included in this prospective first-in-humans translational study. The ICC was 0.84. Graphs of force vs. displacement demonstrated that, for simultaneously acquired measurements involving the same applied force, anterior stromal displacements were lower (suggesting stiffer behavior) than posterior stromal displacements. Mean ka was 0.016±0.004 g/mm and mean kp was 0.014±0.004 g/mm, giving a mean ka/kp ratio of 1.123±0.062., Conclusion: OCE is a clinically feasible, non-invasive corneal biomechanical characterization method capable of resolving depth-dependent differences in corneal deformation behavior. The anterior stroma demonstrated responses consistent with stiffer properties in compression than the posterior stroma, but to a degree that varied across normal eyes. The clinical capability to measure these differences has implications for assessing the biomechanical impact of corneal refractive surgeries and for ectasia risk screening applications., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Matthew R. Ford- Patent (Cleveland Clinic Innovations); William J. Dupps, Jr - Patent (Cleveland Clinic Innovations). This does not alter our adherence to PLOS ONE policies on sharing data and materials.