Our sense of hearing is mediated by cochlear hair cells, localized within the sensory epithelium called the organ of Corti. There are two types of hair cells in the cochlea, which are organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains a few thousands of hair cells, and their survival is essential for our perception of sound because they are terminally differentiated and do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. However, the sheer number of cells along the cochlea makes manual quantification impractical. Machine learning can be used to overcome this challenge by automating the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, human, pig and guinea pig cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 90'000 hair cells, all of which have been manually identified and annotated as one of two cell types: inner hair cells and outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to supply other groups within the hearing research community with the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.

Purpose: To assess a model combining OCT angiography (OCTA) and OCT parameters to predict the severity of paracentral visual field (VF) loss in primary open-angle glaucoma (POAG).Design: Cross-sectional study.Participants: Forty-four patients with POAG and 42 control subjects underwent OCTA and OCT imaging with a swept-source OCT device.Methods: The circumpapillary microvasculature was quantified for vessel density (cpVD) and flow (cpFlow) after delineation of Bruch's membrane opening and removal of large vessels. Retinal nerve fiber layer thickness (RNFLT) and Bruch's membrane opening-minimum rim width (BMO-MRW) were measured from structural OCT. Paracentral total deviation (PaTD) was defined as the average of the total deviation values within the central 10 degrees on Humphrey VF testing (24-2) for upper and lower hemifields. The OCT and OCTA parameters were measured in the affected hemisphere corresponding to the hemifield with lower PaTD for POAG patients. Models were created to predict affected PaTD based on RNFLT alone; RNFLT and BMO-MRW; OCTA alone; or RNFLT, BMO-MRW and OCTA parameters. The models were compared using coefficient of determination (r2) and Bayesian information criterion (BIC) score. Bayesian information criterion decrease of >6 indicates strong evi-dence for model improvement.Main Outcome Measures: Performance of models containing OCT and OCTA parameters in predicting PaTD.Results: Patients with POAG and controls were similar in age and sex (65.9 + 9.5 years and 38.4% male overall, P > 0.56 for both). Average RNFLT, minimum RNFLT, average BMO-MRW, minimum BMO-MRW, cpVD, and cpFlow were all significantly lower (all P < 0.001) in the affected hemisphere in patients with POAG than in controls. In patients with POAG, the average mean deviation was -4.33 + 3.25 dB; the PaTD of the affected hemifield averaged -4.55 + 5.26 dB and correlated significantly with both OCTA and structural OCT parameters (r > 0.43, P < 0.004 for all). The model containing RNFLT, BMO-MRW, and OCTA parameters was superior in predicting affected PaTD (r2= 0.47, BIC = 290.7), with higher r2 and lower BIC compared with all 3 other models.Conclusions: A combined model of OCTA and structural OCT parameters can predict the severity of par-acentral VF loss of the affected hemifield, supporting clinical utility of OCTA in patients with POAG with para -central VF loss.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology Glaucoma 2023;6:255-265 (c) 2022 by the American Academy of Ophthalmology

Since it has been difficult to directly observe the morphology of the living cochlea, our ability to infer the mechanical functioning of the living ear has been limited. Nearly all our knowledge about cochlear morphology comes from postmortem tissue that was fixed and processed using procedures that possibly distort the structures and fluid spaces of the organ of Corti. In this study, optical coherence tomography was employed to obtain volumetric images of the high-frequency hook region of the gerbil cochlea, as viewed through the round window, with far better resolution capability than had been possible before. The anatomical structures and fluid spaces of the organ of Corti were segmented and quantified in vivo and over a 90-min postmortem period. We find that the arcuate-zone and pectinate-zone widths change very little postmortem. The volume of the scala tympani between the round-window membrane and basilar membrane and the volume of the inner spiral sulcus decrease in the first 60-min postmortem. While textbook drawings of the mammalian organ of Corti and cortilymph prominently depict the tunnel of Corti, the outer tunnel is typically missing. This is likely because textbook drawings are typically made from images obtained by histological methods. Here, we show that the outer tunnel is nearly twice as big as the tunnel of Corti or the space of Nuel. This larger outer tunnel fluid space could have a substantial, little-appreciated effect on cochlear micromechanics. We speculate that the outer tunnel forms a resonant structure that may affect reticular-lamina motion.

Purpose To determine the clinical relevance of prelaminar wedge defects (PLWDs) detected by swept-source optical coherence tomography (SS-OCT) in primary open-angle glaucoma (POAG). Materials and Methods In this retrospective case-control study, PLWDs were defined as triangular-shaped defects at the surface of the optic nerve prelaminar tissue, not adjacent to blood vessels, present on cross-sectional SS-OCT scans. Two observers masked to diagnosis independently reviewed scans to detect PLWDs and lamina cribrosa defects. History of disc hemorrhage, occurring within 2 years prior to imaging, was obtained from chart review. One eye per subject was randomly selected. Two-sided t-tests, analysis of variance with Bonferroni correction, and multivariable logistic regression analysis were performed to explore demographic and clinical features associated with PLWDs. Results 40 POAG and 23 control eyes were included. PLWDS were found in 27.5% of POAG (n = 11) and 4.3% of controls (n = 1, p = .04). Eyes with repeat SS-OCT imaging (7 POAG and 0 controls) had persistent PLWDs. More POAG eyes with PLWDs had a history of disc hemorrhage (45.5%) than POAG eyes without PLWDs (3.4%, p = .004). On multivariable analysis, compared to POAG without PLWDs, POAG with PLWDs had increased odds of observed disc hemorrhage (OR = 21.6, 95% CI, 2.2-589.0, p = .02) after adjusting for age, gender, visual field mean deviation and maximum intraocular pressure (IOP). POAG with PLWDs had more lamina cribrosa defects (45.5%) than POAG without PLWDs (3.4%, p = .01) but did not differ significantly from controls (8.7%, p = .07). Compared to all patients without PLWDs, patients with PLWDs had increased odds of having lamina cribrosa defects (OR = 44.8; 95% CI, 6.3-703.6, p < .001) after adjusting for age, gender, and maximum IOP. Conclusions PLWDs were more frequently found in POAG than control eyes and were associated with a history of disc hemorrhage and lamina cribrosa defects. PLWDs may be a useful imaging biomarker of glaucomatous damage.

Because it is difficult to directly observe the morphology of the living cochlea, our ability to infer the mechanical functioning of the living ear has been limited. Nearly all of our knowledge about cochlear morphology comes from postmortem tissue that was fixed and processed using procedures that possibly distort the structures and fluid spaces of the organ of Corti. In this study, optical coherence tomography was employed to obtain in vivo and postmortem micron-scale volumetric images of the high-frequency hook region of the gerbil cochlea through the round-window membrane. The anatomical structures and fluid spaces of the organ of Corti were segmented and quantified in vivo and over a 90-minute postmortem period. The results show that some aspects of the organ of Corti are significantly altered over the course of death, such as the volumes of the fluid spaces, whereas the dimensions of other features change very little. We postulate that the fluid space of the outer tunnel and its surrounding tectal cells form a resonant structure that can affect the motion of the reticular lamina and thereby have a profound effect on outer-hair-cell transduction and thus cochlear amplification. In addition, the in vivo fluid pressure of the inner spiral sulcus is postulated to effectively inflate the connected sub-tectorial gap between the tectorial membrane and the reticular lamina. This gap height decreases after death, which is hypothesized to reduce and disrupt hair-cell transduction

Purpose: To quantify abnormalities in the peripapillary microvasculature in eyes with primary open-angle glaucoma (POAG) and paracentral visual field (VF) loss. Design: Prospective, cross-sectional study. Participants: Thirty-three POAG patients, including 15 with paracentral VF loss and 18 with peripheral VF loss, and 31 control participants underwent swept-source OCT angiography (OCTA) of the peripapillary region. Methods: The POAG groups were matched by VF mean deviation (MD). The peripapillary microvasculature from the internal limiting membrane to the retinal nerve fiber layer (RNFL) interface was quantified within a 0.70-mm annulus around Bruch's membrane opening after removal of large vessels. Both vessel density (VD) and the integrated OCTA by ratio analysis signal (IOS) suggestive of flow were measured. Regional VD and IOS were measured from the affected hemisphere corresponding to the VF hemifield of more severe loss, which was used to calculate the paracentral total deviation (PaTD), or total deviation within the central 10 degrees. One eye per participant was included. Main Outcome Measures: Difference in peripapillary OCTA measurements between paracentral and peripheral VF loss groups and correlation of peripapillary VD and IOS with PaTD. Results: The POAG groups had matched VF MD (-3.1 +/- 2.5 dB paracentral vs. -2.3 +/- 2.0 dB peripheral; P = 0.31), did not differ in average RNFL thickness (71.1 +/- 14.7 mu m vs. 78.1 +/- 15.0 mu m; P = 0.55), but differed in age (59.2 +/- 9.6 years paracentral vs. 67.4 +/- 6.6 years peripheral; P = 0.02). Compared with control participants, both paracentral and peripheral VF loss groups showed reduced VD (P < 0.001 and P = 0.009, respectively) and IOS (P < 0.001 and P = 0.01, respectively) in the affected hemisphere. Compared with POAG eyes with peripheral VF loss, the paracentral group showed reduced peripapillary VD (38.0 +/- 2.0%, 35.0 +/- 2.2%, respectively; P = 0.001) and IOS (44.3 +/- 3.1%, 40.4 +/- 4.0%, respectively; P = 0.02) in the affected hemisphere. Among all POAG eyes, peripapillary VD and IOS of the affected hemisphere correlated significantly with functional measurement of paracentral loss (PaTD, r = 0.40, P = 0.02; r = 0.45, P = 0.008; respectively). These correlations remained significant after adjusting for age (r = 0.41, P = 0.02; r = 0.47, P = 0.01; respectively). Conclusions: Regional peripapillary microvasculature showed decreased VD and flow in POAG with paracentral loss, supporting its importance in this glaucoma subtype. (C) 2020 by the American Academy of Ophthalmology

Glaucoma is the leading cause of irreversible blindness worldwide. Early detection is of utmost importance as there is abundant evidence that early treatment prevents disease progression, preserves vision, and improves patients' long-term quality of life. The structure and function thresholds that alert to the diagnosis of glaucoma can be obtained entirely via digital means, and as such, screening is well suited to benefit from artificial intelligence and specifically machine learning. This paper reviews the concepts and current literature on the use of machine learning for detection of the glaucomatous disc and visual field.

Purpose: To assess optic nerve head (ONH) and peripapillary microvasculature in primary open-angle glaucoma (POAG) of mild to moderate severity using swept-source optical coherence tomography angiography (OCTA). Materials and Methods: In a cross-sectional study, swept-source OCTA images were analyzed for 1 eye from each of 30 POAG patients with glaucomatous Humphrey visual field loss and 16 controls. The anatomic boundary of ONH was manually delineated based on Bruch’s membrane opening and large vessels were removed from en face angiography images to measure vessel density (VD) and the integrated OCTA by ratio analysis signal (IOS), suggestive of flow, in the ONH and peripapillary region. POAG subgroup analysis was performed based on a history of disc hemorrhage (DH) matched by visual field mean deviation (MD). Results: POAG (mean MD±SD, −3.3±3.0 dB) and control groups had similar demographic characteristics and intraocular pressure on the day of imaging. Groups did not differ in superficial ONH VD or flow indicated by IOS (P≥0.28). POAG eyes showed significantly lower VD (39.4%±4.0%) and flow (38.8%±5.6%) in deep ONH, peripapillary VD (37.9%±2.9%) and flow (43.6%±4.0%) compared with control eyes (44.1%±5.1%, 44.7%±6.9%, 40.7%±1.7%, 47.8%±2.5%, respectively; P≤0.007 for all). In the subgroup analysis, POAG eyes with (n=14) and without DH (n=16) had similar measured OCTA parameters (P>0.99 for all). Conclusions: The image processing methodology based on the anatomic boundary of ONH demonstrated compromised microvasculature in the deep ONH and peripapillary region in eyes with mild to moderate POAG, regardless of the history of DH.

Purpose:To evaluate interobserver concordance in measured corneal fluorescein staining (CFS) using the National Eye Institute/Industry (NEI) grading scale and the Corneal Fluorescein Staining Index (CFSi), a computer-assisted, objective, centesimal scoring system.Methods:We conducted a study to evaluate CFS in clinical photographs of patients with corneal epitheliopathy. One group of clinicians graded CFS in the images using the NEI while a second group applied the CFSi. We evaluated the level of interobserver agreement and differences among CFS scores with each method, level of correlation between the two methods, and distribution of cases based on the CFS severity assigned by each method.Results:The level of interobserver agreement was 0.65 (P < 0.001) with the NEI, and 0.99 (P < 0.001) with the CFSi. There were statistically significant differences among clinicians' measurements obtained with the NEI (P < 0.001), but not with the CFSi (P = 0.78). There was a statistically significant correlation between the CFS scores obtained with the two methods (R = 0.72; P < 0.001). The NEI scale allocated the majority of cases (65%) within the higher quartile in the scale's severity (12-15/15). In contrast, the CFSi allocated the majority of cases (61%) within the lower quartile in the scale's severity (0-25/100).Conclusions:The CFSi is easy to implement, provides higher interobserver consistency, and due to its continuous score can discriminate smaller differences in CFS. Reproducibility of the computer-based system is higher and, interestingly, the system allocates cases of epitheliopathy in different severity categories than clinicians do. The CFSi can be an alternative for objective CFS evaluation in the clinic and in clinical trials.

Recent work suggests that hair cells are not the most vulnerable elements in the inner ear; rather, it is the synapses between hair cells and cochlear nerve terminals that degenerate first in the aging or noise-exposed ear. This primary neural degeneration does not affect hearing thresholds, but likely contributes to problems understanding speech in difficult listening environments, and may be important in the generation of tinnitus and/or hyperacusis. To look for signs of cochlear synaptopathy in humans, we recruited college students and divided them into low-risk and high-risk groups based on self-report of noise exposure and use of hearing protection. Cochlear function was assessed by otoacoustic emissions and click-evoked electrocochleography; hearing was assessed by behavioral audiometry and word recognition with or without noise or time compression and reverberation. Both groups had normal thresholds at standard audiometric frequencies, however, the high-risk group showed significant threshold elevation at high frequencies (10-16 kHz), consistent with early stages of noise damage. Electrocochleography showed a significant difference in the ratio between the waveform peaks generated by hair cells (Summating Potential; SP) vs. cochlear neurons (Action Potential; AP), i.e. the SP/AP ratio, consistent with selective neural loss. The high-risk group also showed significantly poorer performance on word recognition in noise or with time compression and reverberation, and reported heightened reactions to sound consistent with hyperacusis. These results suggest that the SP/AP ratio may be useful in the diagnosis of "hidden hearing loss" and that, as suggested by animal models, the noise-induced loss of cochlear nerve synapses leads to deficits in hearing abilities in difficult listening situations, despite the presence of normal thresholds at standard audiometric frequencies.

ABSTRACT Purpose: To compare structural features in prelaminar and laminar tissues of the optic nerve head (ONH) in chronic angle closure glaucoma (CACG), primary open angle glaucoma (POAG), and control subjects. Materials and Methods: ONH imaging was performed using swept-source optical coherence tomography (SS-OCT) for measurements of minimum rim width at Bruch’s membrane opening (BMO-MRW), horizontal, and vertical lamina cribrosa depth (LCD). Prelaminar defects, categorized as hole and wedge, and lamina cribrosa (LC) defects were identified. Enhanced depth imaging spectral domain OCT (EDI-OCT) customized to perform high-resolution volume scans was used in conjunction to further characterize prelaminar holes. One eye per subject was analyzed. Results: Eighty subjects (20 CACG, 40 POAG, and 20 controls) were included in the study. CACG and POAG groups had similar mean deviation on Humphrey visual field testing (−6.9 ± 5.1 vs. −6.3 ± 6.0 dB, p > 0.05) and IOP on the day of imaging (14.0 ± 3.1 vs. 13.8 ± 2.7 mmHg, p > 0.05). Thinnest and global BMO-MRW in CACG (120.3 ± 44.8, 225.5 ± 53.9 μm) and POAG (109.7 ± 56.3, 213.8 ± 59.7 μm) groups were lower than controls (200.1 ± 40.8, 308.3 ± 70.8 μm; p < 0.001 for both). Prelaminar holes were most frequent in CACG (65.0%) than POAG (25.0%, p=0.008) or control groups (20.0%, p=0.01). After adjusting for demographic and ophthalmic covariates, CACG was associated with increased odds of having prelaminar holes compared to POAG (odds ratio, 9.79; 95% CI, 2.12–45.19; p=0.003). Hole volume was similar between CACG and POAG (p > 0.05), but the CACG group had more holes per scan than POAG (maximum 2.5 ± 1.9 vs. 1.2 ± 0.4, p=0.02). Prelaminar wedge defects were less common in the CACG than the POAG group (5.0% vs. 37.5%, p=0.02). The CACG group did not differ from controls in laminar characteristics, such as LCD and LC defects. Conclusions: SS-OCT evaluation of the ONH revealed more frequent prelaminar holes in CACG compared to POAG and control patients.

Aims To compare swept-source optical coherence tomography (SS-OCT) and enhanced depth imaging spectral-domain OCT (EDI-OCT) in quantitative assessment of optic nerve head (ONH) parameters. Methods In a cross-sectional study, patients with primary open angle glaucoma (POAG) and age-matched control subjects underwent SS-OCT and EDI-OCT B-scans of the ONH in a single visit. Two masked readers independently measured the horizontal and vertical lamina cribrosa depth (LCDH and LCDV, respectively), as well as thinnest Bruch's membrane opening minimum rim width (BMO-MRW) from SS-OCT and EDI-OCT scans. We assessed agreement between SS-OCT and EDI-OCT measurements by linear regression models, Bland-Altman analysis and concordance correlation coefficients (CCC). Intrareader and inter-reader reproducibility was assessed using intraclass correlation coefficients (ICC). Results One eye from each of 40 patients with POAG and 20 controls were included. All three ONH measurements were higher on SS-OCT than on EDI-OCT, with significant differences in LCDH (mean difference=31.7 µm, p<0.01) and thinnest BMO-MRW (mean difference=20.5 µm, p<0.01). Linear regression models described the agreement between SS-OCT and EDI-OCT measurements with R2>0.8 for LCDH among both patients with POAG and controls and for thinnest BMO-MRW among patients with POAG. The CCC was >0.8 overall for each parameter. Intrareader and inter-reader ICCs were ≥0.989 and ≥0.964, respectively, for all parameters. Conclusions LCDH, LCDV and thinnest BMO-MRW measurements are not interchangeable between SS-OCT and EDI-OCT, but show good intrareader and inter-reader reproducibility and interdevice agreement for quantitative characterisation of the ONH, particularly among patients with glaucoma.

PURPOSETo evaluate the safety and efficacy of topical pazopanib in the treatment of corneal neovascularization (CNV).METHODSTwenty eyes of 20 patients with stable CNV were enrolled in a prospective, open label, noncomparative study and treated with topical pazopanib 0.5% for 3 weeks, and followed for 12 weeks. The primary endpoint was to determine the tolerability and safety of topical pazopanib in the treatment of CNV defined by the occurrence of ocular and systemic adverse events during the study. The secondary endpoint was to evaluate the effect of topical pazopanib on the reduction of (1) neovascular area (NA), defined as the area of the corneal vessels themselves, (2) invasion area (IA), defined as the fraction of the total cornea into which the vessels extend, (3) vessel length (VL), defined as the mean measurement of the extent of vessels from end to end, and (4) vessel caliber (VC), defined as the mean diameter of the corneal vessels.RESULTSThere were no severe adverse events following the use of topical pazopanib. Compared with the baseline visit, NA and VL showed a statistically significant decrease at week 3 (P = 0.02 and 0.01, respectively); and NA, IA, and VL statistically significantly decreased at week 12 (P = 0.03, 0.04, and <0.01, respectively). Visual acuity maintained without changes after the 12 week follow-up.CONCLUSIONSThis preliminary study suggests that topical treatment with pazopanib 0.5% is safe, well tolerated, and may have a role as an alternative for the treatment of CNV (ClinicalTrials.gov number, NCT01257750).

PURPOSE:To develop and validate a novel automated system to assess ocular redness (OR) in clinical images.METHODS:We developed a novel software that quantifies OR in digital images based on a mathematic algorithm using a centesimal continuous scoring scale. Subsequently, we conducted a study to validate the scores obtained with this system by correlating them with those obtained by two physicians using two image-based comparative subjective scales, the Efron and the Validated Bulbar Redness (VBR) grading scales. Additionally, we evaluated the level of clinical agreement between the Ocular Redness Index (ORI) score and the two image-based methods by means of the Bland-Altman analysis. Main outcome measures included correlation and level of agreement between the ORI score, Efron score, and the VBR score.RESULTS:One hundred and two clinical photographs of eyes with OR were evaluated. The ORI scores significantly correlated with the scores obtained by the two clinicians using the Efron (Observer 1, R=0.925, P<0.001; Observer 2, R=0.857, P<0.001), and VBR (Observer 1, R=0.830, P<0.001; Observer 2, R=0.821, P<0.001) scales. The Bland-Altman analysis revealed levels of disagreement of up to 30 and 27 units for the ORI-Efron and ORI-VBR score comparisons, respectively.CONCLUSIONS:The ORI provides an objective and continuous scale for evaluating ocular injection in an automated manner, and without need for a trained physician for scoring. The ORI may be used as a new alternative for objective OR evaluation in clinics and in clinical trials.

Temporal bone implants can be used to electrically stimulate the auditory nerve, to amplify sound, to deliver drugs to the inner ear and potentially for other future applications. The implants require storage space and access to the middle or inner ears. The most acceptable space is the cavity created by a canal wall up mastoidectomy. Detailed knowledge of the available space for implantation and pathways to access the middle and inner ears is necessary for the design of implants and successful implantation. Based on temporal bone CT scans a method for three-dimensional reconstruction of a virtual canal wall up mastoidectomy space is described. Using Amira® software the area to be removed during such surgery is marked on axial CT slices, and a three-dimensional model of that space is created. The average volume of 31 reconstructed models is 12.6 cm3 with standard deviation of 3.69 cm3, ranging from 7.97 to 23.25 cm3. Critical distances were measured directly from the model and their averages were calculated: height 3.69 cm, depth 2.43 cm, length above the external auditory canal (EAC) 4.45 cm and length posterior to EAC 3.16 cm. These linear measurements did not correlate well with volume measurements. The shape of the models was variable to a significant extent making the prediction of successful implantation for a given design based on linear and volumetric measurement unreliable. Hence, to assure successful implantation, preoperative assessment should include a virtual fitting of an implant into the intended storage space. The above-mentioned three-dimensional models were exported from Amira to a Solidworks application where virtual fitting was performed. Our results are compared to other temporal bone implant virtual fitting studies. Virtual fitting has been suggested for other human applications.