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**Abstract:**



AMA Research Challenge 2023

Intraocular Pressure Reduction comparing Cataract Extraction and Hydrus Microstent Implantation with Cataract Extraction, Canaloplasty, and Hydrus Microstent Implanation

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Automated identification of RIPLs, a potential imaging biomarker of cardiovascular disease

Introduction:
This study explores the feasibility of 3D bioprinting cornea models and contact lenses using digital light processing (DLP) and extrusion printing methods. The goal is to compare the efficiency and results of the BIONOVAX DLP printer and the BIOX6 extrusion printer for potential applications in ophthalmology.

Methods:
Mouse contact lens designs were created using FreeCAD software, and two different materials were used: PEGDA hydrogel for the DLP printer and GelMA collagen-based gel for the extrusion printer. Multiple prints were performed, optimizing parameters to achieve a viable lens structure. Cell viability was assessed by printing with glioblastoma cells and imaging the constructs.

Results:
The BIOX6 printer achieved a more accurate and scalable base curve compared to the BIONOVAX printer. However, the filament diameter of BIOX6 was smaller. BIONOVAX demonstrated a lens thickness of less than 100 microns, while BIOX6 achieved a thickness of 0.21 mm. Print speed differed significantly, with BIONOVAX completing prints in an average of 30 seconds and BIOX6 requiring around 3 minutes.

Conclusion:
BIOX6 showed potential for printing viable lens structures with cells, while BIONOVAX offered higher reliability. Further optimization is needed to enhance the efficiency and replicability of 3D bioprinting. Future research aims to explore different ink properties, optimize lens design, and assess the viability of drug delivery through 3D bioprinted lenses for ocular pathologies like diabetic retinopathy.

Printing the Vision: Advancements in 3D Bioprinting for Cornea and Contact Lens Constructs

Background: Central retinal artery occlusion (CRAO) is associated with painless, unilateral vision loss causing retinal hypoperfusion and ganglion cellular damage. This life-threatening emergency is relatively rare in pediatric populations with causes including trauma, cardiac emboli, and hypercoagulable states. Current evidence-based management for pediatric CRAO is limited, suggesting a critical need to document these isolated presentations. Furthermore, though the patient’s vision is unlikely to be preserved, swift action is essential to prevent death or other comorbidities following CRAO presentation.

Methods: A PubMed search of CRAO in the pediatric population was conducted. Inclusion criteria included patients under 18 years of age at the time of CRAO occurrence with documented fundus findings displaying diffuse central whitening. Branch retinal artery occlusions were excluded. Reporting of CRAO was verified through direct fundus visualization and aided by optical coherence tomography (OCT), fundus photography, and fundus fluorescein angiography. Etiology of CRAO, age, initial and final visual acuity (VA), laterality, follow-up period, workup treatment, and outcome were obtained. A following novel CRAO presentation was included in the study. 

Results: Thirty patients met our inclusion criteria. The mean age of these patients at the initial visit was 11 ± 4.2 years. Visual acuity of 6 patients improved during follow-up, 2 worsened, 8 were unchanged, and 12 patients did not have documented follow-up visual acuity. Average presenting VA was 2.4 ± 0.76 (20/50), and average final VA was 1.54 ± 1.25. The mean LogMAR VA change was -0.26 ± 0.77 over a mean follow-up duration of 18.75 ± 33.01 months. The most common etiologies were thrombotic (8), idiopathic (8), iatrogenic (5), local neoplastic (3), and embolic (3). Notably, pediatric cardiac embolic and systemic thrombotic etiologies were much more common than in the adult population. In contrast, vasculitic and carotid embolic etiologies, the most common causes of adult CRAO, were not seen. The most frequently reported abnormal diagnostic tests were head imaging (16), CBC (complete blood count)/basic metabolic panel (BMP) (11), urinalysis (10), erythrocyte sedimentation rate (ESR)/ C-reactive protein (CRP) (9), and carotid ultrasound or angiogram (7). 

Conclusion: In this review, the most common etiologies of pediatric CRAO were of thrombotic and iatrogenic origin. Our study recommends an initial age-appropriate workup including a magnetic resonance imaging (MRI) of the brain and orbit followed by cardiac imaging, systemic thrombotic workup with head imaging, CBC/BMP, urinalysis, and ESR/CRP.


Systematic Review of Central Retinal Artery Occlusion in Children and Novel Case Presentation

Quantification and Analysis of Laser Peripheral Iridotomies from 2000 to 2021- A National Study

Background

Retinal vascular occlusions (RAVO), such as retinal vein occlusion (RVO) and retinal artery occlusion (RAO), have been shown to be associated with cognitive impairment, including dementia. The purpose of our study is to examine the risk of dementia among patients with retinal vascular occlusion.

Methods

Demographic, clinical, and ophthalmic information was collected for subjects with and without retinal vascular occlusions. 503 subjects with retinal vascular occlusion and 1006 subjects without retinal vascular occlusion (comparison group) seen in an eye clinic were included. Among subjects with retinal vascular occlusions, 432 had retinal vein occlusion (RVO) and 71 had retinal artery occlusion (RAO). Among subjects with retinal vein occlusion, 200 had central RVO (CRVO) and 232 had branch RVO (BRVO). Subjects in the comparison group were age- and sex-matched to those with vascular occlusion. Logistic regression was used to analyze the odds of all-cause dementia, vascular dementia, and Alzheimer’s disease after adjusting for race, ethnicity, diabetes, hypertension, hyperlipidemia, stroke, coronary heart disease, diabetic retinopathy, age-related macular degeneration, and glaucoma.

Results

Subjects with RAVO had increased odds for all-cause dementia (Odds ratio (OR)=2.04, p=0.001) and vascular dementia (OR=2.66, p=0.011). Subjects with RVO had increased odds for all-cause dementia (OR=2.34, p<0.001) and vascular dementia (OR=3.27, p=0.006) relative to the comparison group. Subjects with CRVO (OR=2.34, p=0.013) or BRVO (OR=2.72, p=0.006) had increased odds for all-cause dementia relative to the comparison group. There was no significant association between RAO and the odds for all-cause dementia (OR=1.03, p=0.963).

Conclusion

Central retinal vein occlusions increase the odds of all-cause dementia by over two-fold. Branch retinal vein occlusions increase the odds of all-cause dementia by nearly three-fold. These associations were not seen among patients with retinal arterial occlusions. Retinal vein occlusions also increase the odds of vascular dementia by approximately three-fold.

Risk Factors for Dementia in Patients with Retinal Vein Occlusions

Posterior Cruciate Ligament Reconstruction with Suture Tape Augmentation: A Scoping Review

Background
Cutibacterium, as a ubiquitous, commensal gram-positive organism, represents a diagnostic challenge for arthroplasty surgeons. The characteristics of Cutibacterium culture positivity in THA and TKA are not well understood.

Methods
1: Retrospective chart review of patients with Cutibacterium culture following THA or TKA. 
2: Patient baseline characteristics and lab results were analyzed using T-test and chi-squared analysis. 
3: Those who underwent subsequent surgery were evaluated at one year using MSIS ORT.

Results
Of those with Cutibacterium-positive cultures, 10 of 21 THAs (47.6%) preoperatively met MSIS infection criteria, while 7 of 8 TKAs preoperatively met MSIS criteria (87.5%) (p= 0.13). Mean ESR was 36.4 mm/h for THA and 51.5 mm/h for TKA (p = 0.21), with mean CRP of 35.2 mg/dL for THA and 36.8 mg/dL for TKA (p = 0.95). Mean cell count and percent polymorphonuclear (PMNs) leukocytes from intra-articular aspiration was 27,055 with 68% PMNs for THA and 22,194 with 73.9% PMNs for TKA (p = 0.72 and p = 0.70, respectively). Mean cell count and percent PMNs was 24,143 (range of 95 to 128,205) with 58.9% PMNs for monomicrobial infections and 25,903 with 78.8% PMNs for polymicrobial infections. Of patients who underwent surgical intervention following positive periprosthetic Cutibacterium culture and had one-year follow-up (n =22), 16 (72%) had successful outcomes at one year. Only ASA was significantly different between the success and failure groups.

Conclusion
1) Cutibacterium PJI could lead to more subtle clinical and laboratory changes compared to other microbial species.
2) Patients with Cutibacterium-positive cultures following TKA or THA may not meet MSIS infection criteria.
3) Inflammatory markers and fluid characteristics of Cutibacterium-positive THAs and TKAs were elevated but had more subtle changes compared to accepted values for more virulent microbial species.
4) Patients who undergo surgical intervention following a positive periprosthetic Cutibacterium culture often have successful outcomes at one year.


Patients with Positive Cutibacterium Culture Following Total Hip (THA) and Total Knee Arthroplasty (TKA) Often do not Meet MSIS Criteria for Infection

Background: Noncontact anterior cruciate ligament (ACL) injuries remain a significant problem in young, female athletes who participate in sports involving frequent pivoting. Current risk assessment tools, such as 3D motion analysis of a drop-jump landing, have demonstrated inconsistent ability to identify those who will suffer noncontact ACL injury. Because combinations of unique geometric features of tibiofemoral anatomy (e.g., lateral tibial slope) are related to risk of noncontact ACL injury, physics-based computational models may improve identification of those at heightened risk. Thus, this study had three objectives: 1) to create athlete-specific, 3D, physics-based computational knee models; 2) to estimate ACL forces during a simulated pivot shift loading sequence using these models; and 3) to characterize the relationship between estimated ACL force and risk of first-time, noncontact ACL injury.

Methods: MRI data from 60 female athletes suffering first-time, noncontact ACL rupture and 60 sex-, age-, and sport-matched controls from the same team were utilized. Imaging was obtained on contralateral, uninjured knees of injured athletes, and the same side of matched controls. To accomplish our first objective, volumetric representations of tibiofemoral bone, articular cartilage, and menisci were incorporated into a physics-based computational modeling pipeline. To simulate a pivot shift, we sequentially applied 100 N of compression, an 8 Nm valgus moment, and a 30 N anterior-directed load. At peak applied loads, we recorded estimated ACL force. Logistic regression was used to quantify the risk associated with increased ACL force (α = 0.05).

Results: Estimated ACL forces were, on average, 22.5 N (95% CI: 6.7 – 38.3 N) greater in injured athletes than in their uninjured teammates (mean  SD: 119.0  41.0 N vs. 96.5  42.7 N; p=0.003). Of the 60 injured athletes, 70% (n=42) had greater estimated ACL forces than their uninjured teammates. The odds ratio for each one-SD increase in ACL force was 1.73 (1.18 – 2.55; p=0.005), indicating a 73% increase in likelihood of ACL injury for each one-SD increase in force.

Conclusion: This physics-based computational model revealed significantly greater estimated ACL forces in injured athletes compared to uninjured controls. The use of athlete-specific 3D knee models within our framework allows for detailed investigation of the relationship between knee biomechanics and injury risk with potential utility as a screening tool in female athletes. The association between heightened ACL force and injury risk highlights the importance of addressing unfavorable knee mechanics to enhance injury risk assessment and prevention strategies for female athletes.

Computational Knee Models Reveal Greater Estimated ACL Forces During Simulated Pivot Shift in Female Athletes with Noncontact ACL Injuries: Case-Control Analysis

Pelvic ring fractures (PRF) are rare among all fractures (20/100,000), but have significant associated morbidity and mortality. PRF are often classified into the Young-Burgess classification and the Tile AO classification. The Young-Burgess Classification uses a force vector applied to the pelvic ring to classify the different PRF into lateral (LC), anterior-posterior (APC), and vertical shear (VS). Conversely, the Tile classification is based on stability - Type A, Type B, and Type C. There is limited research that compares these two classification systems. This project consolidates the results of many papers to determine which classification system has better clinical prediction and treatment outcomes and is more reliable. 

Using a systematic approach, PubMed searches were performed using various key words: “Young”, “Burgess”, “Tile”, “presentation”, “treatment”, “pelvic ring” in the Title/Abstract. Only studies on human subjects were included. Studies after 2000 were reviewed to compare reliability of the systems and the clinical outcomes for each classification. Studies after 2013 were included to compare the treatment outcomes of PRFs based on classification. 

Reliability of the classification systems positively correlated with an increase in years of experience. When comparing the reliability, Young-Burgess is shown to have moderate-to-substantial level of agreement for classifying PRFs when accounting for expertise level, while Tile showed substantial agreement between specialists only. For predicting mortality, Young-Burgess is found to be superior to Tile in one study, while another study found no significant difference between the two systems. Another study found that Young-Burgess and Tile systems can be useful in predicting the likelihood of severe injury and communicating with consultants, but cannot reliably predict mortality. Early and appropriate management of PRFs is deemed important since they are associated with life-threatening hemorrhage and are significant causes of morbidity and mortality. Tile B and LC fractures had higher frequency of hemodynamically unstable fractures and underwent laparotomies more frequently than other fracture types. Additionally, Tile B and C, and APC and VS fractures had higher rates of sexual dysfunction in males and females. For treatment options, there was a moderate level of agreement among the surgeons' treatment plans based on radiographic assessment alone, as indicated by a mean kappa value of 0.47. This could have implications for patient care, as different surgeons may have different opinions on the best course of action based on their interpretation of the radiographs. However, the question of whether Young-Burgess and Tile can predict the treatment and the outcome still remains unanswered.

After review of current literature, it appears that Young-Burgess classification has slightly higher reliability and better prediction for mortality than Tile. However, there is a need for further research on how the classification systems can determine the treatment and outcomes to improve morbidity and mortality.


Comparing The Accuracy of Two Pelvic Ring Classification Systems: AO Tile and Young Burgess – A Review of the Literature

Background: As the most popular sport in the world, soccer has driven increased physical demands and higher levels of intensity, resulting in elevated levels of lower extremity injuries among players. Our study analyzed the effects of cleat stud patterns and models worn by players who sustained lower extremity injuries while playing in the English Premier League (EPL). 

Methods: Fifteen cleat models, 510 players, and 221 injuries were analyzed from the EPL 2021-22 season. The injured player cohort was established using Transfermarkt.com, while cleat attributes were obtained from footballbootsdb.com and were confirmed using product websites and online reviews. Odds ratios and confidence intervals were used to assess lower extremity injury risk. Stud patterns or cleat models were set as the experimental condition, with injury or no injury as the outcome.

Results: Our results suggest that very aggressive stud patterns have significantly higher injury odds when directly compared to mildly aggressive. In addition, the odds of players sustaining ankle or knee injuries were significant with very aggressive stud patterns, while the odds of players sustaining hamstring injuries were significant with both very aggressive and non-aggressive. Cleat models with significant total or specific lower extremity injury odds were Nike Mercurial, Adidas X, Nike Phantom GT, Adidas Predator, and Nike Tiempo.

Conclusion: EPL players who wear very aggressive stud patterns may be at higher risk for lower extremity injuries compared to those who wear mildly aggressive stud patterns. Players and clubs should evaluate their footwear choices to best mitigate their injury risk. 


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Intraocular Pressure Reduction comparing Cataract Extraction and Hydrus Microstent Implantation with Cataract Extraction, Canaloplasty, and Hydrus Microstent Implanation

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Automated identification of RIPLs, a potential imaging biomarker of cardiovascular disease

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