Advanced Corneal Imaging in Keratoconus: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the diagnostic capabilities of the newest generation of corneal imaging devices for the identification of keratoconus. METHODS: Corneal imaging devices studied included tomographic platforms (Scheimpflug photography, OCT) and functional biomechanical devices (imaging an air impulse on the cornea). A literature search in the PubMed database for English language studies was last conducted in February 2023. The search yielded 469 citations, which were reviewed in abstract form. Of these, 147 were relevant to the assessment objectives and underwent full-text review. Forty-five articles met the criteria for inclusion and were assigned a level of evidence rating by the panel methodologist. Twenty-six articles were rated level II, and 19 articles were rated level III. There were no level I evidence studies of corneal imaging for the diagnosis of keratoconus found in the literature. To provide a common cross-study outcome measure, diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were extracted. (A perfect diagnostic test that identifies all cases properly has an AUC of 1.0.) RESULTS: For the detection of keratoconus, sensitivities for all devices and parameters (e.g., anterior or posterior corneal curvature, corneal thickness) ranged from 65% to 100%. The majority of studies and parameters had sensitivities greater than 90%. The AUCs ranged from 0.82 to 1.00, with the majority greater than 0.90. Combined indices that integrated multiple parameters had an AUC in the mid-0.90 range. Keratoconus suspect detection performance was lower with AUCs ranging from 0.66 to 0.99, but most devices and parameters had sensitivities less than 90%. CONCLUSIONS: Modern corneal imaging devices provide improved characterization of the cornea and are accurate in detecting keratoconus with high AUCs ranging from 0.82 to 1.00. The detection of keratoconus suspects is less accurate with AUCs ranging from 0.66 to 0.99. Parameters based on single anatomic locations had a wide range of AUCs. Studies with combined indices using more data and parameters consistently reported high AUCs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Safety and Efficacy of Epithelium-Off Corneal Collagen Cross-Linking for the Treatment of Corneal Ectasia: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the safety and effectiveness of epithelium-off corneal collagen cross-linking (CXL) for the treatment of progressive corneal ectasia. METHODS: A literature search of the PubMed database was most recently conducted in March 2024 with no date restrictions and limited to studies published in English. The search identified 359 citations that were reviewed in abstract form, and 43 of these were reviewed in full text. High-quality randomized clinical trials comparing epithelium-off CXL with conservative treatment in patients who have keratoconus (KCN) and post-refractive surgery ectasia were included. The panel deemed 6 articles to be of sufficient relevance for inclusion, and these were assessed for quality by the panel methodologist; 5 were rated level I, and 1 was rated level II. There were no level III studies. RESULTS: This analysis includes 6 prospective, randomized controlled trials that evaluated the use of epithelium-off CXL to treat progressive KCN (5 studies) and post-laser refractive surgery ectasia (1 study), with a mean postoperative follow-up of 2.4 years (range, 1-5 years). All studies showed a decreased progression rate in treated patients compared with controls. Improvement in the maximum keratometry (Kmax) value, corrected distance visual acuity (CDVA), and uncorrected distance visual acuity (UDVA) was observed in the treatment groups compared with control groups. A decrease in corneal thickness was observed in both groups but was greater in the CXL group. Complications were rare. CONCLUSIONS: Epithelium-off CXL is effective in reducing the progression of KCN and post-laser refractive surgery ectasia in most treated patients with an acceptable safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Outcomes and Complications of Limbal Stem Cell Allograft Transplantation: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD). METHODS: Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria. Two studies were rated level II, and the remaining 19 studies were rated level III. There were no level I studies. RESULTS: After KLAL surgery, best-corrected visual acuity (BCVA) improved in 42% to 92% of eyes at final follow-up (range, 12-95 months). The BCVA was unchanged in 17% to 39% of eyes and decreased in 8% to 29% of eyes. Two of 14 studies that evaluated the results of KLAL reported a notable decline in visual acuity over time postoperatively. Survival of KLAL was variable, ranging from 21% to 90% at last follow-up (range, 12-95 months) and decreased over time. For patients undergoing lr-CLAL surgery, BCVA improved in 31% to 100% of eyes at final follow-up (range, 16-49 months). Of the 9 studies evaluating lr-CLAL, 4 reported BCVA unchanged in 30% to 39% of patients, and 3 reported a decline in BCVA in 8% to 10% of patients. The survival rate of lr-CLAL ranged from 50% to 100% at final follow-up (range, 16-49 months). The most common complications were postoperative elevation of intraocular pressure, persistent epithelial defects, and acute allograft immune rejections. CONCLUSIONS: Given limited options for patients with bilateral LSCD, both KLAL and lr-CLAL are viable choices that may provide improvement of vision and ocular surface findings. The studies trend toward a lower rejection rate and graft failure with lr-CLAL. However, the level and duration of immunosuppression vary widely between the studies and may impact allograft rejections and long-term graft survival. Complications related to immunosuppression are minimal. Repeat surgery may be needed to maintain a viable ocular surface. Reasonable long-term success can be achieved with both KLAL and lr-CLAL with appropriate systemic immunosuppression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Spiral scanning improves subject fixation in widefield retinal imaging.

Point scanning retinal imaging modalities, including confocal scanning light ophthalmoscopy (cSLO) and optical coherence tomography, suffer from fixational motion artifacts. Fixation targets, though effective at reducing eye motion, are infeasible in some applications (e.g., handheld devices) due to their bulk and complexity. Here, we report on a cSLO device that scans the retina in a spiral pattern under pseudo-visible illumination, thus collecting image data while simultaneously projecting, into the subject's vision, the image of a bullseye, which acts as a virtual fixation target. An imaging study of 14 young adult volunteers was conducted to compare the fixational performance of this technique to that of raster scanning, with and without a discrete inline fixation target. Image registration was used to quantify subject eye motion; a strip-wise registration method was used for raster scans, and a novel, to the best of our knowledge, ring-based method was used for spiral scans. Results indicate a statistically significant reduction in eye motion by the use of spiral scanning as compared to raster scanning without a fixation target.

Robotic Optical Coherence Tomography Retinal Imaging for Emergency Department Patients: A Pilot Study for Emergency Physicians' Diagnostic Performance.

STUDY OBJECTIVE: To evaluate the diagnostic performance of emergency physicians' interpretation of robotically acquired retinal optical coherence tomography images for detecting posterior eye abnormalities in patients seen in the emergency department (ED). METHODS: Adult patients presenting to Duke University Hospital emergency department from November 2020 through October 2021 with acute visual changes, headache, or focal neurologic deficit(s) who received an ophthalmology consultation were enrolled in this pilot study. Emergency physicians provided standard clinical care, including direct ophthalmoscopy, at their discretion. Retinal optical coherence tomography images of these patients were obtained with a robotic, semi-autonomous optical coherence tomography system. We compared the detection of abnormalities in optical coherence tomography images by emergency physicians with a reference standard, a combination of ophthalmology consultation diagnosis and retina specialist optical coherence tomography review. RESULTS: Nine emergency physicians reviewed the optical coherence tomography images of 72 eyes from 38 patients. Based on the reference standard, 33 (46%) eyes were normal, 16 (22%) had at least 1 urgent/emergency abnormality, and the remaining 23 (32%) had at least 1 nonurgent abnormality. Emergency physicians' optical coherence tomography interpretation had 69% (95% confidence interval [CI], 49% to 89%) sensitivity for any abnormality, 100% (95% CI, 79% to 100%) sensitivity for urgent/emergency abnormalities, 48% (95% CI, 28% to 68%) sensitivity for nonurgent abnormalities, and 64% (95% CI, 44% to 84%) overall specificity. In contrast, emergency physicians providing standard clinical care did not detect any abnormality with direct ophthalmoscopy. CONCLUSION: Robotic, semi-autonomous optical coherence tomography enabled ocular imaging of emergency department patients with a broad range of posterior eye abnormalities. In addition, emergency provider optical coherence tomography interpretation was more sensitive than direct ophthalmoscopy for any abnormalities, urgent/emergency abnormalities, and nonurgent abnormalities in this pilot study with a small sample of patients and emergency physicians.

Systematic analysis of levels of evidence supporting American Academy of Ophthalmology Preferred Practice Pattern guidelines, 2012-2021.

BACKGROUND: Despite the increased emphasis on evidence-based medicine, the current state of evidence behind ophthalmology clinical practice guidelines is unknown. The purpose of this systematic analysis was to understand the levels of evidence (LOE) supporting American Academy of Ophthalmology (AAO) Preferred Practice Pattern (PPP) guidelines, assess changes over time, and compare LOE across ophthalmology subspecialties. METHODS: All current PPP guidelines and their immediate predecessors were comprehensively reviewed to identify all recommendations with LOE provided (I [randomized controlled trials], II [case-control or cohort studies], and III [nonanalytic studies]). RESULTS: Twenty-three out of 24 current PPPs had a prior edition. Among the PPPs with a prior edition, the number of recommendations with LOE decreased from 1254 in prior PPPs to 94 in current PPPs. The number of recommendations with LOE I decreased from 114 to 83, LOE II decreased from 147 to 2, and LOE III decreased from 993 to 9. However, the proportion of LOE I recommendations increased from 9 to 88%, driven by a disproportionate decrease in reporting of evidence lower than LOE I. Subgroup analysis by subspecialty showed similar trends (LOE I recommendations in prior PPPs vs current PPPs: retina: 57 [12%] vs 19 [100%]; cornea: 33 [5%] vs 24 [100%]; glaucoma: 9 [23%] vs 17 [100%]; cataract: 13 [17%] vs 18 [100%]). CONCLUSIONS: Trends in LOE reporting in PPP guidelines indicate an increasing emphasis on evidence from randomized controlled trials from 2012 to 2021. The decline in the number of recommendations with LOE reported suggests an area for improvement in future guidelines as the presence of LOE is crucial to facilitate interpretation of clinical practice guidelines.

QUANTITATIVE TOPOGRAPHIC CURVATURE MAPS OF THE POSTERIOR EYE UTILIZING OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: Deformations of the retina such as staphylomas in myopia or scleral flattening in high intracranial pressure can be challenging to quantify with en face imaging. We describe an optical coherence tomography-based method for the generation of quantitative posterior eye topography maps in normal and pathologic eyes. METHODS: Using "whole eye" optical coherence tomography, we corrected for subjects' optical distortions to generate spatially accurate posterior eye optical coherence tomography volumes and created local curvature (KM, mm-1) topography maps for each consented subject. We imaged nine subjects, three normal, two with myopic degeneration, and four with papilledema including one that was imaged longitudinally. RESULTS: Normal subjects mean temporal KM was 0.0923 mm-1, nasal KM was 0.0927 mm-1, and KM local variability was 0.0162 mm-1. In myopic degeneration, subjects KM local variability was higher at 0.0836 mm-1. In papilledema subjects nasal KM was flatter compared with temporal KM (0.0709 vs. 0.0885 mm-1). Mean intrasession KM repeatability for all subjects was 0.0036 mm-1. CONCLUSION: We have developed an optical coherence tomography based method for quantitative posterior eye topography that offers the ability to analyze local curvature with micron scale resolution and offers the potential to help clinicians and researchers characterize subtle, local retinal deformations earlier in patients and follow their development over time.

Intraocular Lens Implantation in the Absence of Zonular Support: An Outcomes and Safety Update: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the visual acuity results and complications of different surgical techniques for intraocular lens (IOL) implantation in the absence of zonular support. METHODS: Peer-reviewed literature searches were conducted last in PubMed and the Cochrane Library in July 2019. The searches yielded 734 citations of articles published in English. The panel reviewed the abstracts of these mostly retrospective case series studies, and 45 were determined to be relevant to the assessment objectives. Three articles were rated as level II evidence, and 42 articles were rated as level III evidence. RESULTS: Eight different types of IOL fixation techniques with at least 6-month follow-up were evaluated: anterior chamber IOL (ACIOL), iris-claw IOL, retropupillary iris-claw IOL, 10-0 polypropylene iris-sutured posterior chamber IOL (PCIOL), 10-0 polypropylene scleral-sutured PCIOL, 8-0 polypropylene scleral-sutured PCIOL, CV-8 polytetrafluoroethylene, and intrascleral haptic fixation (ISHF). Eight articles reported data comparing 2 techniques. The 45 studies had insufficient statistical power to compare the techniques conclusively. A qualitative analysis of similar types showed that trends in visual acuity outcomes were not inferior to those of ACIOL implantation, but the severity of preoperative pathologic features was not controlled for. Compared with ACIOL, complications of cystoid macular edema were higher in 10-0 polypropylene iris-sutured PCIOL and 8-0 polypropylene scleral-sutured PCIOL. Non-anterior chamber IOL techniques were less likely to report chronic uveitis. Chronic glaucoma was highest in the 8-0 polypropylene scleral-sutured PCIOL group. Although retinal detachment was infrequent overall, it was twice as common in both iris- and scleral-sutured PCIOLs (except CV-8 polytetrafluoroethylene suture) compared with nonsutured methods: ACIOL, iris-clipped IOL, and ISHF PCIOL. CONCLUSIONS: The evidence reviewed shows no superiority of any single IOL implantation technique in the absence of zonular support. The various techniques seem to have equivalent visual acuity outcomes and safety profiles. Each technique has its own profile of inherent risk of postoperative complications. Surgeons must educate patients on the importance of close, long-term follow-up as a result of the uncertain nature of these techniques. Large prospective studies are needed to confirm the long-term complication profiles of these various IOL implantation techniques.

Autologous Serum-Based Eye Drops for Treatment of Ocular Surface Disease: A Report by the American Academy of Ophthalmology.

PURPOSE: To describe the safety and effectiveness of using autologous serum-based eye drops for the treatment of severe dry eye and persistent corneal epithelial defect. METHODS: Literature searches of the PubMed and Cochrane Library databases were conducted most recently in March 2019. The searches identified 281 citations, which were reviewed in abstract form. Of these, 48 were selected for a full-text review, and 13 met the inclusion criteria and were assigned a quality-of-evidence rating by the panel methodologist. Eight of these studies were rated level II and 5 were rated level III; there were no level I studies. RESULTS: This analysis included 10 studies of the use of autologous serum-based eye drops for severe dry eye disease and 4 studies of persistent epithelial defect. Several studies showed good effectiveness, with some improvement in symptoms, signs, or both. Eight of the studies reported improved symptoms for severe dry eye disease, and all noted improvement in at least 1 clinical sign. For persistent epithelial defects, all of the studies showed improvement, with 3 of the 4 demonstrating an improvement rate of more than 90%. Adverse events were rare. CONCLUSIONS: Although autologous serum-based tears may be effective in the treatment of severe dry eye and persistent epithelial defect, conclusions are limited owing to the absence of controlled trials.

Multimodal handheld adaptive optics scanning laser ophthalmoscope.

Non-confocal adaptive optics scanning laser ophthalmoscopy (AOSLO) has enhanced the study of human retinal photoreceptors by providing complementary information to standard confocal AOSLO images. Previously we developed the first confocal handheld AOSLO (HAOSLO) capable of in vivo cone photoreceptor imaging in supine and non-cooperative patients. Here, we introduce the first multimodal (M-)HAOSLO for confocal and non-confocal split-detection (SD) imaging to allow for more comprehensive patient data collection. Aside from its unprecedented miniature size and weight, M-HAOSLO is also the first system to perform sensorless wavefront-corrected SD imaging of cone photoreceptors.

Topography and pachymetry maps for mouse corneas using optical coherence tomography.

The majority of the eye's refractive power lies in the cornea, and pathological changes in its shape can affect vision. Small animal models offer an unparalleled degree of control over genetic and environmental factors that can help elucidate mechanisms of diseases affecting corneal shape. However, there is not currently a method to characterize the corneal shape of small animal eyes with topography or pachymetry maps, as is done clinically for humans. We bridge this gap by demonstrating methods using optical coherence tomography (OCT) to generate the first topography and pachymetry (thickness) maps of mouse corneas. Radii of curvature acquired using OCT were validated using calibration spheres as well as in vivo mouse corneas with a mouse keratometer. The resulting topography and pachymetry maps are analogous to those used diagnostically in clinic and potentially allow for characterization of genetically modified mice that replicate key features of human corneal disease.

Optical Coherence Tomography-Guided Robotic Ophthalmic Microsurgery via Reinforcement Learning from Demonstration.

Ophthalmic microsurgery is technically difficult because the scale of required surgical tool manipulations challenge the limits of the surgeon's visual acuity, sensory perception, and physical dexterity. Intraoperative optical coherence tomography (OCT) imaging with micrometer-scale resolution is increasingly being used to monitor and provide enhanced real-time visualization of ophthalmic surgical maneuvers, but surgeons still face physical limitations when manipulating instruments inside the eye. Autonomously controlled robots are one avenue for overcoming these physical limitations. We demonstrate the feasibility of using learning from demonstration and reinforcement learning with an industrial robot to perform OCT-guided corneal needle insertions in an ex vivo model of deep anterior lamellar keratoplasty (DALK) surgery. Our reinforcement learning agent trained on ex vivo human corneas, then outperformed surgical fellows in reaching a target needle insertion depth in mock corneal surgery trials. This work shows the combination of learning from demonstration and reinforcement learning is a viable option for performing OCT guided robotic ophthalmic surgery.

An Update of Eye Shape and Myopia.

Myopia is one of the most prevalent eye diseases, and its advanced form, high myopia, is a leading cause of subsequent pathologic myopia, which in turn results in an increased risk of retinal diseases. The prevalence of myopia and high myopia is 28.3% and 4.0% of the global population, respectively, and these numbers are estimated to increase to 49.8% for myopia 9.8% for high myopia by 2050, thus making myopia a severe global socioeconomic problem. The eye shape has been receiving increasing attention as a possible biomarker for myopia. Among several modalities, magnetic resonance imaging (MRI) is currently considered to be the best to measure the 3-dimensional eye shape, and one study using MRI revealed that myopic eyes became much larger in all 3 dimensions, but more so in length (0.35 mm/D) than in height (0.19 mm/D) or in width (0.10 mm/D), which fitted in global and axial elongation models. Another recent study reported that emmetropic retinas were oblate but oblateness decreased with myopia progression. According to a study to evaluate eye shapes in high myopia, although all emmetropic eyes had a blunt shape, almost half of the high myopic eyes had a pointed shape. Multiple lines of evidence suggest that abnormal eye shape changes can cause not only simple myopia but also various ocular complications through biomechanical stretching. In this review, we highlight recent findings on eye shape changes in myopic eyes and abnormal eye shapes in pathologic myopia.

Descemet Membrane Endothelial Keratoplasty: Safety and Outcomes: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the safety and outcomes of Descemet membrane endothelial keratoplasty (DMEK) for the surgical treatment of corneal endothelial dysfunction. METHODS: Literature searches were last conducted in the PubMed and the Cochrane Library databases most recently in May 2017. The searches, which were limited to English-language abstracts, yielded 1085 articles. The panel reviewed the abstracts, and 47 were determined to be relevant to this assessment. RESULTS: After DMEK surgery, the mean best-corrected visual acuity (BCVA) ranged from 20/21 to 20/31, with follow-up ranging from 5.7 to 68 months. At 6 months, 37.6% to 85% of eyes achieved BCVA of 20/25 or better and 17% to 67% achieved BCVA of 20/20 or better. Mean endothelial cell (EC) loss was 33% (range, 25%-47%) at 6 months. Overall change in spherical equivalent was +0.43 diopters (D; range, -1.17 to +1.2 D), with minimal induced astigmatism of +0.03 D (range, -0.03 to +1.11 D). The most common complication was partial graft detachment requiring air injection (mean, 28.8%; range, 0.2%-76%). Intraocular pressure elevation was the second most common complication (range, 0%-22%) after DMEK, followed by primary graft failure (mean, 1.7%; range, 0%-12.5%), secondary graft failure (mean, 2.2%; range, 0%-6.3%), and immune rejection (mean, 1.9%; range, 0%-5.9%). Overall graft survival rates after DMEK ranged from 92% to 100% at last follow-up. Best-corrected visual acuity after Descemet's stripping endothelial keratoplasty (DSEK) ranged from 20/34 to 20/66 at 9 months. The most common complications after DSEK were graft detachment (mean, 14%; range, 0%-82%), endothelial rejection (mean, 10%; range, 0%-45%), and primary graft failure (mean, 5%; range, 0%-29%). Mean EC loss after DSEK was 37% at 6 months. CONCLUSIONS: The evidence reviewed supports DMEK as a safe and effective treatment for endothelial failure. With respect to visual recovery time, visual outcomes, and rejection rates, DMEK seems to be superior to DSEK and to induce less refractive error with similar surgical risks and EC loss compared with DSEK. The rate of air injection and repeat keratoplasty were similar in DMEK and DSEK after the learning curve for DMEK.

Method for single illumination source combined optical coherence tomography and fluorescence imaging of fluorescently labeled ocular structures in transgenic mice.

In vivo imaging permits longitudinal study of ocular disease processes in the same animal over time. Two different in vivo optical imaging modalities - optical coherence tomography (OCT) and fluorescence - provide important structural and cellular data respectively about disease processes. In this Methods in Eye Research article, we describe and demonstrate the combination of these two modalities producing a truly simultaneous OCT and fluorescence imaging system for imaging of fluorescently labeled animal models. This system uses only a single light source to illuminate both modalities, and both share the same field of view. This allows simultaneous acquisition of OCT and fluorescence images, and the benefits of both techniques are realized without incurring increased costs in variability, light exposure, time, and post-processing effort as would occur when the modalities are used separately. We then utilized this system to demonstrate multi-modal imaging in a progression of samples exhibiting both fluorescence and OCT scattering beginning with resolution targets, ex vivo thy1-YFP labeled neurons in mouse eyes, and finally an in vivo longitudinal time course of GFP labeled myeloid cells in a mouse model of ocular allergy.

Optical coherence tomography accurately measures corneal power change from laser refractive surgery.

PURPOSE: To determine the ability of motion-corrected optical coherence tomography (OCT) to measure the corneal refractive power change due to LASIK. DESIGN: Evaluation of a diagnostic test or technology in a cohort. SUBJECTS: A total of 70 eyes from 37 subjects undergoing LASIK were measured preoperatively. A total of 39 eyes from 22 subjects were measured postoperatively and completed the study. METHODS: Consecutive patients undergoing LASIK at the Duke Eye Center who consented to participate were imaged with Placido-ring topography, Scheimpflug photography, and OCT on the day of their surgery. Patients were then reimaged with the same imaging systems at the postoperative month 3 visit. Change in preoperative to postoperative corneal refractive power as measured by each of the imaging modalities was compared with the preoperative to postoperative change in manifest refraction (MRx) using the t test with generalized estimating equations. MAIN OUTCOME MEASURES: Corneal refractive power change due to LASIK as measured by Placido-ring topography, Scheimpflug photography, and OCT compared with the MRx change vertexed to the corneal plane. The change in MRx should correspond to the change in the corneal refractive power from LASIK and was considered the reference measurement. RESULTS: In 22 individuals (39 eyes) returning after LASIK, we found no significant difference between the clinically measured pre- to post-LASIK change in MRx and both Scheimpflug photography (P = 0.714) and OCT (P = 0.216). In contrast, keratometry values from Placido-ring topography were found to be significantly different from the measured refractive change (P < 0.001). In addition, of the 3 imaging modalities, OCT recorded the smallest mean absolute difference from the reference measurement with the least amount of variability. CONCLUSIONS: Motion-corrected OCT more accurately measures the change in corneal refractive power due to laser refractive surgery than other currently available clinical devices. By offering accurate corneal refractive power measurements in normal and surgically modified subjects, OCT offers a compelling alternative to current clinical devices for determining corneal refractive power.

Identification of Keratoconus-Related Phenotypes in Three Ppip5k2 Mouse Models.

Purpose: It is necessary to establish a mouse model of keratoconus (KC) for research and therapy. We aimed to determine corneal phenotypes in 3 Ppip5k2 mouse models. Methods: Central corneal thickness (CCT) was determined using spectral domain optical coherence tomography (SD-OCT) in Ppip5k2+/K^ (n = 41 eyes), Ppip5k2K^/K^ (n = 17 eyes) and 2 knock-in mice, Ppip5k2S419A/+ (n = 54 eyes) and Ppip5k2S419A/S419A (n = 18 eyes), and Ppip5k2D843S/+ (n = 42 eyes) and Ppip5k2D843S/D843S (n = 44 eyes) at 3 and 6 months. Pachymetry maps were generated using the Mouse Corneal Analysis Program (MCAP) to process OCT images. Slit lamp biomicroscopy was used to determine any corneal abnormalities, and, last, hematoxylin and eosin (H&E) staining using corneal sections from these animals was used to examine morphological changes. Results: CCT significantly decreased from 3 to 6 months in the Ppip5k2+/K^ and Ppip5k2K^/K^ mice compared to their littermate controls. OCT-based pachymetry maps revealed abnormally localized thinning in all three models compared to their wild-type (WT) controls. Slit lamp examinations revealed corneal abnormalities in the form of bullous keratopathy, stromal edema, stromal scarring, deep corneal neovascularization, and opacities in the heterozygous/homozygous mice of the three models in comparison with their controls. Corneal histological abnormalities, such as epithelial thickening and stromal layer damage, were observed in the heterozygous/homozygous mice of the three models in comparison with the WT controls. Conclusions: We have identified phenotypic and histological changes in the corneas of three mouse lines that could be relevant in the development of animal models of KC.

RobOCTNet: Robotics and Deep Learning for Referable Posterior Segment Pathology Detection in an Emergency Department Population.

Purpose: To evaluate the diagnostic performance of a robotically aligned optical coherence tomography (RAOCT) system coupled with a deep learning model in detecting referable posterior segment pathology in OCT images of emergency department patients. Methods: A deep learning model, RobOCTNet, was trained and internally tested to classify OCT images as referable versus non-referable for ophthalmology consultation. For external testing, emergency department patients with signs or symptoms warranting evaluation of the posterior segment were imaged with RAOCT. RobOCTNet was used to classify the images. Model performance was evaluated against a reference standard based on clinical diagnosis and retina specialist OCT review. Results: We included 90,250 OCT images for training and 1489 images for internal testing. RobOCTNet achieved an area under the curve (AUC) of 1.00 (95% confidence interval [CI], 0.99-1.00) for detection of referable posterior segment pathology in the internal test set. For external testing, RAOCT was used to image 72 eyes of 38 emergency department patients. In this set, RobOCTNet had an AUC of 0.91 (95% CI, 0.82-0.97), a sensitivity of 95% (95% CI, 87%-100%), and a specificity of 76% (95% CI, 62%-91%). The model's performance was comparable to two human experts' performance. Conclusions: A robotically aligned OCT coupled with a deep learning model demonstrated high diagnostic performance in detecting referable posterior segment pathology in a cohort of emergency department patients. Translational Relevance: Robotically aligned OCT coupled with a deep learning model may have the potential to improve emergency department patient triage for ophthalmology referral.

Quantitative single and multi-surface clinical corneal topography utilizing optical coherence tomography.

Successful surgical treatment of ocular astigmatism requires accurate characterization of both magnitude and axis of the astigmatism. Keratometry and topography are clinically widely used for this measurement; however, their analysis is limited to the anterior corneal surface. Unlike these techniques, optical coherence tomography (OCT) offers the advantage of measuring both the anterior and posterior corneal surface contributions. We present a technique to combine the local curvatures of both surfaces into a single pseudosurface suitable for clinical application. Building on prior work in distributed scanning OCT (DSOCT) to remove corrupting patient motion artifacts, we present the results of a pilot patient study where extracted values of clinical corneal astigmatic power magnitude and direction from DSOCT corneal volumes were comparable to standard clinical measures of corneal astigmatism.

Preclinical evaluation and intraoperative human retinal imaging with a high-resolution microscope-integrated spectral domain optical coherence tomography device.

PURPOSE: The authors have recently developed a high-resolution microscope-integrated spectral domain optical coherence tomography (MIOCT) device designed to enable OCT acquisition simultaneous with surgical maneuvers. The purpose of this report is to describe translation of this device from preclinical testing into human intraoperative imaging. METHODS: Before human imaging, surgical conditions were fully simulated for extensive preclinical MIOCT evaluation in a custom model eye system. Microscope-integrated spectral domain OCT images were then acquired in normal human volunteers and during vitreoretinal surgery in patients who consented to participate in a prospective institutional review board-approved study. Microscope-integrated spectral domain OCT images were obtained before and at pauses in surgical maneuvers and were compared based on predetermined diagnostic criteria to images obtained with a high-resolution spectral domain research handheld OCT system (HHOCT; Bioptigen, Inc) at the same time point. Cohorts of five consecutive patients were imaged. Successful end points were predefined, including ≥80% correlation in identification of pathology between MIOCT and HHOCT in ≥80% of the patients. RESULTS: Microscope-integrated spectral domain OCT was favorably evaluated by study surgeons and scrub nurses, all of whom responded that they would consider participating in human intraoperative imaging trials. The preclinical evaluation identified significant improvements that were made before MIOCT use during human surgery. The MIOCT transition into clinical human research was smooth. Microscope-integrated spectral domain OCT imaging in normal human volunteers demonstrated high resolution comparable to tabletop scanners. In the operating room, after an initial learning curve, surgeons successfully acquired human macular MIOCT images before and after surgical maneuvers. Microscope-integrated spectral domain OCT imaging confirmed preoperative diagnoses, such as full-thickness macular hole and vitreomacular traction, and demonstrated postsurgical changes in retinal morphology. Two cohorts of five patients were imaged. In the second cohort, the predefined end points were exceeded with ≥80% correlation between microscope-mounted OCT and HHOCT imaging in 100% of the patients. CONCLUSION: This report describes high-resolution MIOCT imaging using the prototype device in human eyes during vitreoretinal surgery, with successful achievement of predefined end points for imaging. Further refinements and investigations will be directed toward fully integrating MIOCT with vitreoretinal and other ocular surgery to image surgical maneuvers in real time.