Comparison of Machine and Human Expert Evaluation of Capsulorrhexis Creation Performance Through Analysis of Surgical Video Recordings.

Purpose: Achieving competency in cataract surgery is an essential component of ophthalmology residency training. Video-based analysis of surgery can change training through its objective, reliable, and timely assessment of resident performance. Methods: Using the Image Labeler application in MATLAB, the capsulorrhexis step of 208 surgical videos, recorded at the University of Michigan, was annotated for subjective and objective analysis. Two expert surgeons graded the creation of the capsulorrhexis based on the International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric:Phacoemulsification (ICO-OSCAR:phaco) rating scale and a custom rubric (eccentricity, roundness, size, centration) that focuses on the objective aspects of this step. The annotated rhexis frames were run through an automated analysis to obtain objective scores for these components. The subjective scores were compared using both intra and inter-rater analyses to assess the consistency of a human-graded scale. The subjective and objective scores were compared using intraclass correlation methods to determine relative agreement. Results: All rhexes were graded as 4/5 or 5/5 by both raters for both items 4 and 5 of the ICO-OSCAR:phaco rating scale. Only roundness scores were statistically different between the subjective graders (mean difference = -0.149, p-value = 0.0023). Subjective scores were highly correlated for all components (>0.6). Correlations between objective and subjective scores were low (0.09 to 0.39). Conclusion: Video-based analysis of cataract surgery presents significant opportunities, including the ability to asynchronously evaluate performance and provide longitudinal assessment. Subjective scoring between two raters was moderately correlated for each component.

Dystrophic Calcification in a 3-Piece Silicone Intraocular Lens.

This case report describes a diagnosis of dystrophic calcification of a silicone intraocular lens implant in a patient who presented with foggy vision and glare.

The effect of social determinants of health on severity of microbial keratitis presentation at a tertiary eye care hospital in Southern India.

Purpose: Understanding the association between social determinants of health (SDoHs) and microbial keratitis (MK) can inform underlying risk for patients and identify risk factors associated with worse disease, such as presenting visual acuity (VA) and time to initial presentation. Methods: This was a cross-sectional study was conducted with patients presenting with MK to the cornea clinic at a tertiary care hospital in Madurai, India. Patient demographics, SDoH survey responses, geographic pollution, and clinical features at presentation were collected. Descriptive statistics, univariate analysis, multi-variable linear regression models, and Poisson regression models were utilized. Results: There were 51 patients evaluated. The mean age was 51.2 years (SD = 13.3); 33.3% were female and 55% did not visit a vision center (VC) prior to presenting to the clinic. The median presenting logarithm of the minimum angle of resolution (logMAR) VA was 1.1 [Snellen 20/240, inter-quartile range (IQR) = 20/80 to 20/4000]. The median time to presentation was 7 days (IQR = 4.5 to 10). The average particulate matter 2.5 (PM2.5) concentration, a measure of air pollution, for the districts from which the patients traveled was 24.3 µg/m3 (SD = 1.6). Age- and sex-adjusted linear regression and Poisson regression results showed that higher levels of PM2.5 were associated with 0.28 worse presenting logMAR VA (Snellen 2.8 lines, P = 0.002). Patients who did not visit a VC had a 100% longer time to presentation compared to those who did (incidence rate ratio = 2.0, 95% confidence interval = 1.3-3.0, P = 0.001). Conclusion: Patient SDoH and environmental exposures can impact MK presentation. Understanding SDoH is important for public health and policy implications to mitigate eye health disparities in India.

Effect of topical bovine colostrum in wound healing of corneal surface after acute ocular alkali burn in mice.

The purpose of this study was to evaluate the effect of bovine colostrum (BC) in the regeneration of corneal epithelial cells on an ocular alkali burn model. Twenty-four C57BL/6 mice were categorized into two gender/age-matched groups for treatment. Two days after inducing a corneal alkali burn in all left eyes with 4 µl of sodium hydroxide 0.15 mol/l, both eyes of group 1 were treated with BC 4 times per day, and both eyes of group 2 were treated with isotonic saline solution (SS). The epithelial defect was photographed and measured by fluorescein staining on days two, four, seven, and ten. Ocular burn damage was assessed with a pre-established classification in clock hours from the limbus. After 10 days both eyes were processed, half of the group's corneas were assessed histopathologically, and the other half was used for pro/anti-inflammatory cytokine quantification using ELISA. BC treated (Group 1) corneas revealed significantly improved fluorescein staining score for limbal involvement when compared to SS treated (Group 2) corneas at days 4 (p = 0.013), 7 (p < 0.001), and 10 (p < 0.001), respectively. No differences were noted in limbal involvement at day 2 between the two groups (p > 0.99). The overall change (difference in slope) in fluorescein staining for limbal involvement between days 2 and 10 was -0.1669 (p = 0.006). Histologic examinations and cytokine measurements of group 2 demonstrated a strong inflammatory component compared to group 1. Our data indicates that topical application of BC facilitates corneal re-epithelialization and wound healing by suppressing the inflammatory process in an ocular alkali burn model.

Analysis of Cataract Surgery Instrument Identification Performance of Convolutional and Recurrent Neural Network Ensembles Leveraging BigCat.

Purpose: To develop a method for accurate automated real-time identification of instruments in cataract surgery videos. Methods: Cataract surgery videos were collected at University of Michigan's Kellogg Eye Center between 2020 and 2021. Videos were annotated for the presence of instruments to aid in the development, validation, and testing of machine learning (ML) models for multiclass, multilabel instrument identification. Results: A new cataract surgery database, BigCat, was assembled, containing 190 videos with over 3.9 million annotated frames, the largest reported cataract surgery annotation database to date. Using a dense convolutional neural network (CNN) and a recursive averaging method, we were able to achieve a test F1 score of 0.9528 and test area under the receiver operator characteristic curve of 0.9985 for surgical instrument identification. These prove to be state-of-the-art results compared to previous works, while also only using a fraction of the model parameters of the previous architectures. Conclusions: Accurate automated surgical instrument identification is possible with lightweight CNNs and large datasets. Increasingly complex model architecture is not necessary to retain a well-performing model. Recurrent neural network architectures add additional complexity to a model and are unnecessary to attain state-of-the-art performance. Translational Relevance: Instrument identification in the operative field can be used for further applications such as evaluating surgical trainee skill level and developing early warning detection systems for use during surgery.

Descemet membrane endothelial keratoplasty in a patient with iris-fixated intraocular lens and prior radial keratotomy: a case report.

BACKGROUND: Anterior segment surgeries such as cataract surgery, intraocular lens (IOL) repositioning, and radial keratotomy (RK) may hasten endothelial dysfunction, particularly in the context of pre-existing Fuchs dystrophy, necessitating future corneal transplantation. CASE PRESENTATION: A 68-year-old woman with a history of RK with associated irregular astigmatism in both eyes and iris-fixated intraocular lens (IF-IOL) in the left eye presented with six months of decreased vision in the left eye. She was found to have Fuchs dystrophy and underwent DMEK surgery. She had an uncomplicated postoperative course, with uncorrected visual acuity improving to 20/20 three months after surgery. CONCLUSION: To our knowledge, this is the first reported case of a highly successful DMEK surgery in a patient with prior RK and IF-IOL.

Optical Coherence Tomography Assessment of the Cornea During Corneal Swelling: Should the Term "Descemet Membrane Folds" Be Reconsidered?

PURPOSE: Previous work has suggested that Descemet membrane (DM) folds arise in response to corneal swelling. However, their origin has not been closely explored. In this study, we used optical coherence tomography to evaluate whether DM folds arise secondary to folds in the middle stroma. METHODS: Serial optical coherence tomography images of donor cornea pairs in deionized water were taken for each of the following corneal manipulations: 1) untreated, 2) DM and the endothelium removed, 3) excised in the region of the deep middle/posterior stroma, and 4) excised in the middle stroma. RESULTS: For intact corneas, increasing duration in deionized water was marked by a progressive increase in corneal thickness and number of folds along the posterior surface. With DM and the endothelium removed, a similar phenomenon was observed. In the third set of corneas, the plane of resection created a structural separation in the region of the deep middle/posterior stroma. Folds were seen originating anterior to the resection plane. For corneas with the posterior and part of the middle stroma removed, the typical folds on the posterior surface as seen in the previous conditions were not observed. Instead, less numerous and smaller irregularities of the posterior surface of the resection plane were present. CONCLUSIONS: Folds in DM associated with corneal edema originate in the middle and posterior stroma and are secondarily transmitted into DM. On the basis of the stromal origin of these anatomic changes, "stromal folds" should be considered a more accurate term to replace "Descemet membrane folds."

Comparison of self-refraction using a simple device, USee, with manifest refraction in adults.

BACKGROUND: The USee device is a new self-refraction tool that allows users to determine their own refractive error. We evaluated the ease of use of USee in adults, and compared the refractive error correction achieved with USee to clinical manifest refraction. METHODS: Sixty adults with uncorrected visual acuity <20/30 and spherical equivalent between -6.00 and +6.00 diopters completed manifest refraction and self-refraction. RESULTS: Subjects had a mean (±SD) age of 53.1 (±18.6) years, and 27 (45.0%) were male. Mean (±SD) spherical equivalent measured by manifest refraction and self-refraction were -0.90 D (±2.53) and -1.22 diopters (±2.42), respectively (p = 0.001). The proportion of subjects correctable to ≥20/30 in the better eye was higher for manifest refraction (96.7%) than self-refraction (83.3%, p = 0.005). Failure to achieve visual acuity ≥20/30 with self-refraction in right eyes was associated with increasing age (per year, OR: 1.05; 95% CI: 1.00-1.10) and higher cylindrical power (per diopter, OR: 7.26; 95% CI: 1.88-28.1). Subjectively, 95% of participants thought USee was easy to use, 85% thought self-refraction correction was better than being uncorrected, 57% thought vision with self-refraction correction was similar to their current corrective lenses, and 53% rated their vision as "very good" or "excellent" with self-refraction. CONCLUSION: Self-refraction provides acceptable refractive error correction in the majority of adults. Programs targeting resource-poor settings could potentially use USee to provide easy on-site refractive error correction.

Effects of Contrast Sensitivity on Colour Vision Testing.

This study analyses how contrast sensitivity loss affects colour vision (CV) testing. Eleven participants were scored while cycling through randomly arranged pictures of CV tests with varying levels of contrast changes applied. Hardy-Rand-Rittler (HRR) scores declined significantly at each successive decrease in contrast level after the highest setting (p < 0.004). HRR scores were also lower than those for Ishihara and Farnsworth D-15 tests at two contrast settings (p < 0.01). Contrast changes had the greatest impact on HRR scores, indicating that this test may not be an accurate reflection of CV in patients with contrast sensitivity loss.

Ganetespib radiosensitization for liver cancer therapy.

Therapies for liver cancer particularly those including radiation are still inadequate. Inhibiting the stress response machinery is an appealing anti-cancer and radiosensitizing therapeutic strategy. Heat-shock-protein-90 (HSP90) is a molecular chaperone that is a prominent effector of the stress response machinery and is overexpressed in liver cancer cells. HSP90 client proteins include critical components of pathways implicated in liver cancer cell survival and radioresistance. The effects of a novel non-geldanamycin HSP90 inhibitor, ganetespib, combined with radiation were examined on 3 liver cancer cell lines, Hep3b, HepG2 and HUH7, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γH2AX foci kinetics and client protein expression in pathways important for liver cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined ganetespib-radiation treatment on tumor cell proliferation in a HepG2 hind-flank tumor graft model. Nanomolar levels of ganetespib alone exhibited liver cancer cell anti-cancer activity in vitro as shown by decreased clonogenic survival that was associated with increased apoptotic cell death, prominent G2-M arrest and marked changes in PI3K/AKT/mTOR and RAS/MAPK client protein activity. Ganetespib caused a supra-additive radiosensitization in all liver cancer cell lines at low nanomolar doses with enhancement ratios between 1.33-1.78. These results were confirmed in vivo, where the ganetespib-radiation combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in HepG2 tumor grafts. Our data suggest that combined ganetespib-radiation therapy exhibits promising activity against liver cancer cells, which should be investigated in clinical studies.

Structure-function studies of the bHLH phosphorylation domain of TWIST1 in prostate cancer cells.

The TWIST1 gene has diverse roles in development and pathologic diseases such as cancer. TWIST1 is a dimeric basic helix-loop-helix (bHLH) transcription factor existing as TWIST1-TWIST1 or TWIST1-E12/47. TWIST1 partner choice and DNA binding can be influenced during development by phosphorylation of Thr125 and Ser127 of the Thr-Gln-Ser (TQS) motif within the bHLH of TWIST1. The significance of these TWIST1 phosphorylation sites for metastasis is unknown. We created stable isogenic prostate cancer cell lines overexpressing TWIST1 wild-type, phospho-mutants, and tethered versions. We assessed these isogenic lines using assays that mimic stages of cancer metastasis. In vitro assays suggested the phospho-mimetic Twist1-DQD mutation could confer cellular properties associated with pro-metastatic behavior. The hypo-phosphorylation mimic Twist1-AQA mutation displayed reduced pro-metastatic activity compared to wild-type TWIST1 in vitro, suggesting that phosphorylation of the TWIST1 TQS motif was necessary for pro-metastatic functions. In vivo analysis demonstrates that the Twist1-AQA mutation exhibits reduced capacity to contribute to metastasis, whereas the expression of the Twist1-DQD mutation exhibits proficient metastatic potential. Tethered TWIST1-E12 heterodimers phenocopied the Twist1-DQD mutation for many in vitro assays, suggesting that TWIST1 phosphorylation may result in heterodimerization in prostate cancer cells. Lastly, the dual phosphatidylinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor BEZ235 strongly attenuated TWIST1-induced migration that was dependent on the TQS motif. TWIST1 TQS phosphorylation state determines the intensity of TWIST1-induced pro-metastatic ability in prostate cancer cells, which may be partly explained mechanistically by TWIST1 dimeric partner choice.

Novel Hsp90 inhibitor NVP-AUY922 radiosensitizes prostate cancer cells.

Outcomes for poor-risk localized prostate cancers treated with radiation are still insufficient. Targeting the "non-oncogene" addiction or stress response machinery is an appealing strategy for cancer therapeutics. Heat-shock-protein-90 (Hsp90), an integral member of this machinery, is a molecular chaperone required for energy-driven stabilization and selective degradation of misfolded "client" proteins, that is commonly overexpressed in tumor cells. Hsp90 client proteins include critical components of pathways implicated in prostate cancer cell survival and radioresistance, such as androgen receptor signaling and the PI3K-Akt-mTOR pathway. We examined the effects of a novel non-geldanamycin Hsp90 inhibitor, AUY922, combined with radiation (RT) on two prostate cancer cell lines, Myc-CaP and PC3, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γ-H2AX foci kinetics and client protein expression in pathways important for prostate cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined treatment (RT-AUY922) on the PI3K-Akt-mTOR and AR pathways in a hind-flank tumor graft model. We observed that AUY922 caused supra-additive radiosensitization in both cell lines at low nanomolar doses with enhancement ratios between 1.4-1.7 (p < 0.01). RT-AUY922 increased apoptotic cell death compared with either therapy alone, induced G 2-M arrest and produced marked changes in client protein expression. These results were confirmed in vivo, where RT-AUY922 combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in Myc-CaP and PC3 tumor grafts (both p < 0.0001). Our data suggest that combined RT-AUY922 therapy exhibits promising activity against prostate cancer cells, which should be investigated in clinical studies.