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2022 AMA Research Challenge

Comparing FA and OCTA evaluation of retinal vascularity of murine eyes with diabetic retinopathy with Contrast-Limited Adaptive Histogram Equalization (CLAHE) and Matched Filter Image Processing Technique

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Welcome to the largest national, multi-specialty research event **featuring research from 750 medical students, residents and fellows, and international medical graduates.**


#### Event Details
The 2022 American Medical Association Research Challenge includes a poster symposium hall and a semifinals hall with the top scored research. Log in at any time throughout the event to:
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At the conclusion of this event, the AMA will announce the top five finalists who will advance to the AMA Research Challenge finals, present their research to an elite panel of judges and compete to win a $10,000 grand prize sponsored by Laurel Road.
 

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Ricardo Correa, MD, EdD
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Stuart M. Greenstein, MD
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Stephanie Strohbeen, MD
 
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Jessica Li, MD/PhD Candidate
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Charles Lopresto, DO

### Sponsor
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Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


Background: 
Dry Eye Syndrome (DES) is a multifactorial disorder of the ocular surface, characterized by inadequate moisture and subsequent discomfort, pain, or visual disturbances. DES is associated with increased corneal dendritic cell (DC) density, a marker of inflammation. Treatments proposed to decrease inflammation in DES currently lack quantitative evidence. This study investigated the effects of cyclosporine eye drops on corneal DC density using in vivo confocal microscopy (IVCM). Our hypothesis is that topical cyclosporine treatment will reduce inflammation as demonstrated by decreased DC density.

Methods:
In this prospective study, central cornea images for DES patients were obtained with IVCM (HRT III RCM). Images were taken prior to and three months after treatment with either cyclosporine 0.05% or 0.09% twice daily in both eyes. A semi-automated cell count software was used to analyze dendritic cells (DCs) in the sub-basal nerve plexus. A student t-test was conducted to compare DC density before and after treatment.

Results:
20 eyes of 10 patients (7 women; mean age 56 ± 22 years) completed the study. 16 eyes and 4 eyes were treated with cyclosporine 0.05% and 0.09% respectively. One eye was excluded due to poor image quality. Mean DC density was 64.63 ± 81.48 cells/mm2 at baseline and 50.36 ± 61.86 cells/mm2 after three months of treatment. There was an average DC density decrease of 14.26 ± 44.95 cells/mm2 after treatment. 12 eyes showed decreased corneal DC density and 7 eyes showed either no detectable change or increased DC density. For eyes treated with cyclosporine 0.05% and 0.09%, the mean difference between baseline and post-intervention was a non-statistically significant decrease of 3.00 ± 25.56 cells/mm2 (p=0.92) and 56.50 ± 77.87 cells/mm2 (p=0.24) respectively.

Conclusion: 
Topical cyclosporine is known to be effective in treating DES, but its microstructural effects on ocular surface inflammation have not been quantified. In this study, IVCM was used to quantify cyclosporine’s effects on reducing corneal DC density in dry eyes. Further investigation is necessary to elucidate this potentially dose-related effect.

Effect of Topical Cyclosporine on Dendritic Cell Density in Patients with Dry Eye Syndrome Using In Vivo Confocal Microscopy

Abstract Title: Morphological and Vascular Features of the Optic Nerve in Healthy Asians

Background: Glaucoma is the second leading cause of blindness worldwide, impacting nearly 3 million patients in the US and 80 million globally. Glaucoma is characterized by progressive optic neuropathy, which leads to structural and vascular damage to the optic nerve (ON) and retina. A novel technology, known as optical coherence tomography angiography (OCTA), captures both the structure and vascular features of the retina and ON. Previous studies have indicated that blacks with large optic discs (ODs) experience a more severe form of glaucoma. Information about OD size and glaucoma in Asians is not well documented. Therefore, the aim of our study was to evaluate morphological and vascular features of the OD in healthy South Asian (SA India), East Asian (EA- China), and Southeast Asian (SEA- Vietnam) patients using OCTA scans.

Methods: In this IRB approved, retrospective, age-matched study conducted at an academic center, we reviewed OCTA scans from 76 healthy subjects who were self-identified as SA, SEA, or EA. Exclusion criteria included high myopia/hyperopia, poor scan quality and vitreoretinal disorders. We measured mean disc area, rim area, cup/disc ratio, and vessel densities on the ON. Data was analyzed with pairwise Student’s two-tailed t-tests.

Results: After exclusions, 46 patients [33 (62 eyes) SA, 4 (8 eyes) EA, 9 (16 eyes) SEA] were included. The mean disc vertical size of SEA was higher than SA (1.84mm vs. 1.73mm, p=0.016). The mean disc area in SEA was higher than that in SA (2.49mm² vs. 2.25mm², p=0.024). There were no differences in measurements between SA and EA or EA and SEA. Peripapillary vessel density was significantly higher in SA than in EA (52.2% vs. 50.2%, p=0.036). All other measurements were not significant.

Conclusion: Our pilot study has shown that disc area and disc vertical size are greater in SEA than SA, potentially making them more prone to glaucomatous damage. We believe that these OD ethnic differences, if further investigated, could serve as early markers of glaucoma in healthy Asian eyes.

Morphological and Vascular Features of the Optic Nerve in Healthy Asians

Purpose: To describe OCT findings in pediatric uveitis patients and analyze visual acuity changes over time.

Methods: A retrospective chart review of pediatric patients (0 to 18 years old) seen at the Emory Eye Center between 2008 and June 2020 with a diagnosis of uveitis and OCT imaging available was conducted. Data collected included demographic data, uveitis etiology, anatomical uveitis location, best-corrected visual acuity (BCVA), findings on OCT, and treatment.

Results: There were 204 patients and 327 eyes with a diagnosis of pediatric uveitis and at least one OCT on record. The average age was 11.5 years with 57% females (116), 43% Black (87) and 33% Caucasian (68). 137 (67%) patients had bilateral uveitis with the majority, 194 (95%), with a non-infectious etiology. Anatomical location of uveitis was anterior, intermediate, anterior/intermediate, posterior, or panuveitis in 42%, 24%, 9%, 10%, and 15% respectively. At baseline on OCT, there were 222 normal eyes, 19 eyes with an epiretinal membrane (ERM), 53 eyes with macular edema, 14 eyes with both macular edema and ERM, and 19 eyes with subretinal fibrosis. On mixed model analysis controlling for the correlation that exists between eyes of the same subject, the worst initial BCVA was seen in eyes with epiretinal membrane and macular edema, followed by macular edema eyes, subretinal fibrosis, and eyes with an ERM with a logMAR BCVA of 0.95, 0.75, 0.73, and 0.50 respectively (p<0.0001). Notably, with most abnormal OCT findings, BCVA improved over 24 months except for ERM eyes, which showed a logMAR BCVA change of 0.50 to 0.60 (p<0.0001). In a sub-analysis of patients with macular edema with or without subretinal fluid (SRF), there was no difference between baseline clinical characteristics or BCVA in patients who had SRF.

Conclusions: OCT imaging in pediatric uveitis is important for diagnosis and monitoring progression of sight- threatening complications. Pediatric uveitis cases show a high proportion of bilateral involvement and prevalence of complications leading to worse BCVA, which demonstrates that prompt treatment and continued monitoring via OCT imaging can prevent ocular sequelae leading to blindness.

Optical coherence tomography (OCT) findings in a pediatric uveitis cohort

Purpose: Orbital exenteration involves removal of the entire orbital contents including the globe. It is typically reserved for orbital malignancies, the incidence of which have increased. This study aims to evaluate the demographics of patients undergoing orbital exenteration, as well as survival based on disease, status of surgical margins, and surgical technique. 

Methods: Retrospective chart review.

Results: Patients undergoing exenteration were on average 62.7 years old, and the majority were male (63.8%). The most common diagnoses were squamous (41.8%), basal (15.4%), and sebaceous cell carcinoma (11.0%). Total exenteration (59.8%) was the most common surgical technique, and reconstruction was most often performed with a skin graft (60.0%). 20.7% of patients demonstrated tumor recurrence and 17.7% showed metastasis. Additionally, 25.3% of patients demonstrated surgical complications on an average of 12.6 months after the procedure. Most patients were treated with adjuvant therapy (57.1%), most of whom underwent radiation therapy (56.3%). Survival was significantly higher amongst basal cell carcinoma and adenoid cystic carcinoma patients than those with mucormycosis (40.4 and 28.5 vs. 1.8 months) (p=.05). Patients with positive surgical margins (39.4%) showed significantly higher tumor recurrence than those without (35.7% vs 9.5%, p<.01). There was no significant difference in survival based on surgical margins or techniques (p>0.5). 

Conclusion: With an aging population, the incidence of invasive orbital and adnexal tumors has increased over time. Our results support prior literature by suggesting that survival is highly dependent on the predisposing disease, and positive surgical margins significantly increase the risk for tumor recurrence and/or metastasis. There was no statistically significant difference in survival based on surgical or reconstruction technique, which suggests we can successfully perform partial exenterations, including lid-sparing surgery, without affecting disease course and survival. Many patients presenting with advanced disease may have a wider range of treatment options in favor of radical surgery.

Orbital Exenteration at Bascom Palmer Eye Institute: 2002-2021

The use of silicone oil (SO) during rhegmatogenous retinal detachment (RRD) surgery allows for prolonged retinal tamponade. While SO removal (SOR) is performed to optimize visual function, there are incompletely defined risks such as re-detachment (re- RD) associated with SOR. The current study characterizes rates of re-RD and functional outcomes following SOR.
Data was retrospectively collected from an urban retina practice with 14 physicians. Inclusion criteria were SO placement (SOP) during an RRD repair followed by SOR from 2016-2021. Exclusion criteria were vitreoretinal surgery performed outside the current practice and post-operative follow-up periods of <3 months. Analyzed parameters included epidemiological data, intraoperative variables, and post-operative outcomes. Statistical analysis included one-way ANOVA with Tukey HSD testing (significance defined as p<0.05).
89 eyes of 88 patients underwent SOR following 31 RRD repair with SOP. 77 of 89 eyes (86.5%) did not undergo further RRD surgery following SOR; of this group, 2 eyes did not achieve reattachment due to persistent subretinal fluid (SRF) and 1 eye underwent enucleation due to Proteus spp. panophthalmitis. Additional RRD repairs were required by 12 of 89 eyes (13.5%); of this group, 2 eyes received gas tamponade while 10 eyes received SOP in re-surgeries. 9 of 10 eyes receiving SOP a second time did not undergo further SOR, while 1 eye proceeded successfully with a second SOR. Only 1 of 12 eyes experiencing an additional RRD repair remained unattached due to persistent SRF. Visual acuity (VA) among eyes without additional RRD repairs following SOR improved by 0.32logMAR from SOR (baseline VA) to final follow-up (p<0.05), while VA among eyes undergoing 31 additional RRD repair minimally improved or worsened from baseline.
This study characterized re-RD rates and visual outcomes among eyes undergoing SOR after RRD repair. VA improvement was observed among eyes that did not undergo additional surgeries following SOR. Further work comparing the risks of re-RD with the functional benefits following SOR may help guide clinical management.

Outcomes of Eyes Undergoing Silicone Oil Removal Following ComplexRhegmatogenous Retinal Detachment Repair

Background: Glaucoma is the second leading cause of blindness affecting over 3 million Americans and 80 million worldwide. Glaucoma is a progressive optic neuropathy affecting both the structure and vascular supply of the optic nerve and retina. Optical Coherence Tomography Angiography (OCTA) is a new non-invasive imaging technique which provides 3D volumetric information on the structure and vascular networks of the optic nerve and retina. However, OCTA artifacts can reduce the quality of scans, and their prevalence is not well known. Therefore, the aim of our study was to investigate the prevalence and severity of OCTA artifacts in healthy (H), ocular hypertension (OHT), glaucoma suspect (GS), primary open angle glaucoma (POAG), and moderate/severe myopia (M) patients.

Methods: In this IRB-approved, retrospective, age-matched study conducted at an academic center, we selected consecutive single-eye OCTA scans in 292 patients (50 H, 30 OHT, 32 GS, 90 POAG, 90 M) between January-June 2021. Patients with severe retinal disease, dementia, tremors, and secondary angle closure glaucoma were excluded. We classified artifacts as either patient-related motion artifacts (MA) or operator/machine-related image artifacts (IA). The artifacts were scored as 1, 0, -1 (none, some, & severe, respectively) and sub-classified within MA (eye movement, blinking, crisscross, and refraction error) and IA (decentration, defocus, projection, segmentation, cropping, and shadow). Chi-square and Cramer's V analysis were utilized to assess differences between groups.

Results: Essentially every patient (99.3%) had at least 1 artifact, and severe artifacts were found in 25.8% of scans. Compared to H, severe artifacts were seen in patients with POAG and M (18% vs. 32.8% and 31.1%, respectively; p < 0.001). The most prevalent artifacts overall were eye movement (66.1%), defocus (64.7%), projection (48.6%), and shadow (40.1%).

Conclusion: Our study is among the first to report prevalence of OCTA artifacts in those with glaucoma or myopia. Although OCTA is a powerful tool in diagnosis and management of glaucoma, a high prevalence of artifacts can limit clinical interpretation. Further research to minimize both patient-related and machine-related artifacts must be conducted.

Prevalence of Artifacts in Optical Coherence Tomography Angiography in Glaucoma and Myopia

Background: Retinal vein occlusion (RVO) is the second most common cause of blindness among retinal vascular diseases. It consists of central retinal artery occlusion (CRAO), central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). While the regional prevalence of RVO in the U.S. is 0.5 to 2 %, the national rate is still unknown. Therefore, we utilized a nationally representative sample collected by the National Health and Nutrition Examination Survey (NHANES) to better estimate the national prevalence and risk factors for
RVO.
Methods: The NHANES is a multi-ethnic study, which surveyed individuals from 30 different counties across the U.S. between 2005-2008. Besides demographic and medical diseases survey, participants underwent 45 degrees non-mydriatic retinal photography of both eyes. Out of 7081 cases, 1552 were excluded due to missing and ungradable images. For the remaining 5559 participants (2771 men and 2788 women), retinal scans were masked and evaluated by graders for the presence of RVO. We performed weighted analysis to estimate national prevalence rates and multivariate analysis to examine associated risk factors. 
Results: Out of 5559 subjects, 33 (20 men and 13 women, 0.59%) had RVO [27 (0.48%) BRVO, and 6 (0.11%) CRVO]. The overall national prevalence of BRVO, CRVO, and any RVO was 0.42% (95% CI = 0.23—0.60), 0.08% (95% CI = 0—0.18), and 0.50% (95% CI = 0.30—0.71), respectively. Multivariate analysis found that age, per 10-year increase (OR, 1.93; 95% CI = 1.31—2.92, P = 0.001) and elevated diastolic blood pressure, per 10 mm Hg increase (OR, 1.47; 95% CI = 1.10—2.12, P = 0.032) were significant risk factors for the prevalence of RVO. Race, gender, history of diabetes, stroke, and cardiovascular disease were not found to be significant risk factors. In univariate analysis glaucoma (P = 0.009) and total cholesterol (P =0.021) were significantly associated with RVO.
Conclusion: Our study found that the overall national prevalence of RVO was 0.50%. In addition, older age and elevated diastolic BP were strongly associated with RVO. We recommend that patients with these characteristics undergo regular comprehensive ocular examination.

Prevalence of Retinal Vein Occlusion in the United States

Background
Glaucoma, the second leading cause of blindness, affects over 80 million patients worldwide, including 3 million patients in the USA. It is a progressive optic neuropathy affecting both the structure and vascular supply of the optic nerve and retina. Optical coherence tomography angiography (OCTA) is a new, noninvasive technique which excels at providing the vasculature and anatomy of these regions. Recent studies have demonstrated a possible link between vessel area density (VAD) and glaucoma progression. However, conflicting data indicates a need for more robust study of VAD and other quantitative parameters such as vessel length density (VLD) and branchpoint density (BPD). Therefore, our aim was to analyze and compare these three parameters in patients with primary open angle glaucoma (POAG) and healthy subjects using open-source ImageJ software.

Methods
This IRB-approved, retrospective study included 98 consecutive participants (49 healthy; 49 POAG) imaged at an academic center between January and May 2020. One eye was chosen at random from each subject. Exclusion criteria included OCTA scan quality < 6/10, significant artifacts, high myopia/hyperopia, and vitreoretinal diseases. We analyzed the superficial and deep plexuses of the retina as well as the radial peripapillary capillary (RPC) layer of the optic disc. VAD, VLD, and BPD were obtained for each layer using ImageJ and the relationship between healthy and glaucomatous eyes was analyzed via logistic regression. Diagnostic value
was determined using areas under receiver operating curves (AUC).

Results
VAD, VLD, and BPD were significantly reduced in glaucoma for all anatomical layers, with the greatest reduction occurring in the RPC layer (P < 0.001). The AUCs of the diagnostic models analyzing all parameters within the superficial, deep, and RPC layers were 0.883, 0.902, and 0.942, respectively. Combining all parameters from all layers into a single model yielded the best diagnostic performance (AUC = 0.974; p < 0.001).

Conclusion
Our study is among the first to quantitatively characterize OCTA scans of healthy and glaucomatous eyes using multiple parameters. Our combined model analyzing multiple ocular layers has shown excellent utility in the diagnosis of glaucoma.

Vascular Morphology of the Optic Nerve and Retina in Glaucoma

Background:
Acetabular fractures are highly complex injuries often resulting from high-energy trauma that orthopedic surgeons commonly address and treat. The use of open reduction internal fixation (ORIF) has increased in recent years and is highly technical, in that the quality of ORIF directly affects patient outcome. Studies have characterized multiple factors that contribute to post- operative quality of life. The purpose of this study is to further this understanding and investigate how (1) patient demographics and (2) patient-specific risk factors affect 90-day readmissions in patients.
Methods:
A retrospective, nationwide query of private insurance database from January 1st, 2010 to October 31st, 2020 was performed using ICD-9, ICD-10, and CPT codes. Patients who underwent acetabular fracture ORIF for acetabular fractures and were readmitted within 90 days following index procedure were included, while those patients who were not readmitted served as comparison controls, yielding a total of 3942 patients. Patients were divided by demographics (age and sex) and specific risk factors associated with readmission. A logistic regression model was used to identify the odds ratio (OR) and 95% confidence interval. Alpha-value of less than 0.002 was considered statistically significant.
Results:
The query yielded a total of 3,942 patients. Age and sex were found to be non-significant contributing risk factors to 90-day readmissions (p = 0.251 and p = 0.531, respectively). Data also showed that statistically significant co-morbidities included arrhythmia (OR:1.32, 1.16-1.78, p< 0.0001), cerebrovascular disease (OR: 1.43, OR: 1.43, CI: 1.16-1.78, p< 0.0001), coagulopathy (OR: 1.62, 1.30-2.02, p < 0.0001), fluid and electrolyte abnormalities (OR: 1.52, CI: 1.25-1.84, p< 0.0001), and pathologic weight loss (OR: 1.37, CI: 1.10-1.70, p< 0.0001). 
Conclusion:
This study illustrated how several patient-specific risk factors may contribute to increased 90-day readmission risk following acetabular ORIF. A heightened awareness of these comorbidities in patients requiring acetabular ORIF is required to improve patient outcomes and minimize rates of readmission. Further investigation is needed to optimize quality of ORIF in these patient populations, improve patient outcomes, and increase awareness of potential postoperative complications in these higher-risk patient populations.

Comparison of Patient Demographics and Patient Specific Risk Factors for Readmissions Following Open Reduction and Internal Fixation for Acetabular Fractures

Background: Although technology-assisted total knee arthroplasty (TKA) is becoming increasingly prevalent, insight into its reception by the public is limited. Here we evaluate the public’s perception of technology-assisted TKA compared to traditional TKA.

Methods: A prospective cohort study was performed utilizing a paid survey distributed via a validated online marketplace. Following baseline demographics, participants were queried whether they would prefer a computer-/robotic-assisted (technology) TKA or traditional TKA without additional information. Participants were separated into “Tech TKA” and “Traditional TKA” cohorts based on their responses. All respondents sequentially completed a pre-test, an evidence-based education table, and a post-test survey focused on the differences between technology versus traditional TKA. Upon completion, cohorts were again asked which TKA modality they would prefer. Statistical tests performed included Student’s t-tests and χ2 tests.

Results: 500 surveys were completed with 402 (80.4%) respondents in the tech TKA and 98 (19.6%) in the traditional TKA cohort. Tech TKA respondents were more educated (Bachelor’s degree: 46.88% vs 31.63%, p<.01), had higher incomes (>$75,000: 35.6% vs 18.4%), and more familiar with TKA (know of, very familiar, or underwent TKA: 93.2% vs 82.65%; p<.01;. Age, gender, race, ethnicity, and annual doctor visits were similar.

After reviewing the educational table, 33 (33.67%) of the traditional TKA respondents switched their preferences to technology TKA. Conversely, 95 (23.63%) Tech TKA switched to traditional TKA. Among post-test respondents interested in technology-assisted TKA, 75.00% were willing to switch their surgeons and 35.29% would pay an additional sum of moneys if not covered by insurance (35.29%). The most important information from the table for technology-assisted TKA respondents was length of stay, while traditional TKA was “who does the surgery.”

Conclusion: Technology-assisted TKA appears to be well-regarded and valued amongst the public. Educational material does not appear to dramatically change preferences.

Assessing Patient Preferences for Technology-Assisted versusTraditional Total Knee Arthroplasty Using a Validated Online SurveyMarketplace: Before and After Patient Education

Comparing FA and OCTA evaluation of retinal vascularity of murine eyes with diabetic retinopathy with Contrast-Limited Adaptive Histogram Equalization (CLAHE) and Matched Filter Image Processing Technique

Next from 2022 AMA Research Challenge

Effect of Topical Cyclosporine on Dendritic Cell Density in Patients with Dry Eye Syndrome Using In Vivo Confocal Microscopy

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