UH Ophthalmology Research Day 2022

OPHTHALMOLOGY RESIDENT, FELLOW AND MEDICAL STUDENT RESEARCH DAY SYMPOSIUM 2022 Saturday, May 21, 2022 7:30 AM-12:30 PM Wolstein Research Building Case Western Reserve University

PRESENTERS

SESSIONS & KEYNOTE PRESENTATION TIME

SESSION

7:30 AM – 7:55 AM

Registration and Continental Breakfast

7:55 AM

Opening Remarks Douglas Rhee, MD, Professor and Chairman, Ophthalmology & Visual Science

8:00 AM- 9:12 AM

Session I Moderated by Douglas Rhee, MD

9:12 AM

Introduction of Keynote Speaker Jonathan Lass, MD

9:14 AM

Keynote Speaker Presentation New Insights into Diagnosis and Treatment of Fuchs Dystrophy Ula V. Jurkunas, MD Associate Professor of Ophthalmology Harvard Medical School Staff Member, Cornea Service Massachusetts Eye and Ear Infirmary

10:00 AM

Break

10:15 AM- 11:27 AM

Session II Moderated by Jonathan Lass, MD

11:27 AM

Break

11:37 AM

Session III Moderated by Faruk Örge, MD

12:13 PM

Closing Remarks Douglas Rhee, MD

PRESENTERS

KEYNOTE SPEAKER

Ula Jurkunas, MD Dr. Ula Jurkunas is a clinician-scientist in the Cornea and Refractive Surgery Service at Mass Eye and Ear and an Associate Professor of Ophthalmology at Harvard Medical School. She conducts basic science and clinical research on Fuchs endothelial corneal dystrophy and stem cell transplantation of the ocular surface. In addition, she teaches residents and fellows about corneal surgical procedures as well as diagnosis and clinical management of corneal and refractive conditions. Her main clinical areas of expertise are corneal endothelial dysfunction, femtosecond cataract surgery, refractive surgery, and lamellar keratoplasty, including DMEK and complex DSAEK.

Dr. Jurkunas heads a fully-staffed and RO1-NIH funded laboratory, which studies the mechanisms involved in the corneal endothelial degeneration seen in Fuchs dystrophy. Her studies focus on the role of oxidative stress in cell-extracellular matrix interactions, estrogen metabolism, DNA damage and repair, and mitochondrial biogenesis in Fuchs dystrophy.

Currently Dr. Jurkunas is working on an UG1 NIH/NEI grant and performing the first-in-human study using Cultivated Autologous Limbal Epithelial Cells (CALEC) transplantation at Mass Eye and Ear, in collaboration with Cell Manufacturing Facility at Dana-Farber Cancer Institute. Her work has led to numerous peer-reviewed publications, review articles, and both national and international presentations. Dr. Jurkunas has received numerous awards, including Research to Prevent Blindness Award, ARVO Alcon Early Clinician-Scientist Research Award, Alcon Research Institute Award, AAO Achievement Award, and, most recently, ARVO Foundation/Pfizer Ophthalmics Carl Camras Translational Research Award. She serves as Co-Director of Harvard Medical School’s Department of Ophthalmology Cornea Center of Excellence. She previously served for five years on the Editorial Board of Investigative Ophthalmology & Visual Science.

PRESENTERS

PROGRAM SCHEDULE 8:00 AM- 9:12 AM

Session I – Moderator: Douglas Rhee, MD

8:00 AM

Lily Kim, MD, Resident, PGY 4, Ophthalmology & Visual Sciences Micropulse Cyclophotocoagulation: A Moving Target Project Mentor: Dr. Shands

8:12 AM

Stephen Lau, MD, Glaucoma Fellow, Ophthalmology & Visual Services Implant and Non-Implant Minimally Invasive Glaucoma Surgery Outcomes with Concurrent Cataract Extraction in Moderate Severity Glaucoma Project Mentor: Dr. Sozeri

8:24 AM

Archana Murali, Medical Student, CWRU SOM Immunoblot Analysis of Lymphatic Marker Expression in Human Ciliary Body Cells Followng Prostaglandin Analog Treatment Project Mentor: Dr. Rhee

8:36 AM

Roy Swanson, MD, Resident, PGY 4, Ophthalmology & Visual Sciences LPI Patient Characteristics and Selection Criteria at the Cleveland VA Project Mentor: Dr. Kapadia

8:48 AM

Kunal Suri, MD, Resident, PGY 4, Ophthalmology & Visual Services Factors associated with Severity of Bacterial Keratitis in Contact Lens Wearers; a Multi-Center Study Project Mentor: Dr. Szczotka-Flynn

9:00 AM

Soham Shah, Medical Student, CWRU SOM Evaluation of Risk Factors for Bacterial Keratitis in Soft Contact Lens Users Compared to a High-Risk Cohort; a Multi-Center Case Control Study Project Mentor: Dr. Szczotka-Flynn

9:12 AM

Introduction of Keynote Speaker Johnathan Lass, MD

9:14 AM

Keynote Speaker: Ula V. Jurkunas, MD New Insights into Diagnosis and Treatment of Fuchs Dystrophy

10:00 AM

Break

PRESENTERS

PROGRAM SCHEDULE 11:15 AM

Session II- Moderator: Jonathan Lass, MD

11:15 AM

Tarek Tabbaa, MD, Resident, PGY 3, Ophthalmology & Visual Services Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy (ADNIV): A Case Series with Multimodal Imaging Project Mentor: Dr. Sobol

11:15 AM

David Shieh, MD, Resident, PGY 3, Ophthalmology & Visual Sciences The Role of Inflammatory Cytokines in the Development and Progression of Diabetic Retinopathy in VA patients Project Mentor: Dr. Sobol

11:15 AM

Blanche Kuo, Medical Student, CWRU SOM Association of long term real-world visual acuity outcomes and number of anti-VEGF injections in patients with diabetic macular edema: 6-year follow-up using the IRIS® Registry Project Mentor: Drs. R. Singh and K. Talcott

11:15 AM

Lalita Gupta, MD, Resident, PGY 4, Ophthalmology & Visual Sciences Management of Thyroid Eye Disease Before and After the Approval of Teprotumumab: Orbital Decompression Rates at Multiple Academic Centers Project Mentor: Dr. Prendes

11:15 AM

Kambiz Ghiam, MD, Resident, PGY 3, Ophthalmology & Visual Sciences Surgical Outcomes after Frontalis Suspension using ePTFE Sling for Congenital Ptosis Project Mentor: Dr. Örge

11:15 AM

Andrew Pasquale, MD, Resident, PGY 3, Ophthalmology & Visual Sciences Deep Learning AI for Prediction of Malignant Orbital Project Mentor: Dr. Prendes

11:27 AM

Break

PRESENTERS

PROGRAM SCHEDULE 11:37 AM-12:13 AM

Session III– Moderator: Faruk Örge

11:37 AM

Richard Helms, MD, PhD, Resident, PGY 3, Ophthalmology & Visual Services Could Rare Earth Magnets be Used to Treat a 'Lost' Medial Rectus Muscle?

Project Mentor: Dr. Abrams

11:49 AM

John Wang, MD, Resident, PGY 4, Ophthalmology & Visual Services Do Horizontal Rectus Muscle Recessions need a Correction Factor with Oblique Muscle Involvement?

Project Mentor: Dr. Örge

12:01 PM

12:13 PM

Zeina Salem, MD, Fellow, Pediatric Ophthalmology, Ophthalmology & Visual Sciences Strabismus Surgical Database Results Project Mentor: Dr. Örge Concluding Remarks Doughlas Rhee, MD

PRESENTERS

ABSTRACTS

Presented by: Lily Kim Hipp, MD Project Mentor: Philip Shands, MD Purpose: Micropulse cyclophotocoagulation (mCPC) is a relatively new tool for intraocular pressure (IOP) reduction, and even newer at the Veteran’s Administration in Cleveland, OH where it is being utilized as a novel option for patients who are poor surgical candidates but still with functionally useful vision. This is contrast to the conventional continuous-wave cyclophotocoagulation, which delivers continuous energy and is associated with higher rates of complications including loss of visual acuity, hypotony, and chronic inflammation. Due to its relatively recent induction parameters such as power, duration of treatment, and number of quadrants treated are highly physician-independent. The purpose of this study is to determine the outcomes of micropulse cyclophotocoagulation (mCPC) in regards to reduction of IOP in relation to total energy delivered. The outcomes of repeat mCPC will also be investigated to assess for efficacy in IOP reduction and compared to the outcomes of first-time mCPC. Methods: This is a single-center, multiple surgeon retrospective case series performed at the Louis Stokes Cleveland Department of Veteran Affairs in Cleveland, Ohio. We performed chart review on all patients with severe glaucoma who underwent mCPC from 6/2019 to 4/2022. We excluded patients with less than one week of postoperative follow up or who previously underwent conventional CPC, and excluded data after additional surgical intervention or after death. Statistical analysis was performed with MS-Excel software and GraphPad. The standard Cyclo G6 Glaucoma Laser System (Iridex) parameters were utilized: 2000mW to 2500mW with duty cycle 31.3% ranging from 60 to 120 second per hemisphere.

Results: The total number of eyes undergoing mCPC was 37, including first time and repeat patients. The number of first-time mCPC eyes were 24, and total repeat eyes were 13. All patients were male. Average baseline IOP prior to mCPC was 23.86 +/ 7.67 mmHg amongst all 38 eyes; in mCPC naiive patients it was 24.4mmHg +/8.251mmHg and 22.46 mmHg +/- 6.31 in repeat-mCPC patients.

The average length of follow up was 12.05 +/- 8.18 weeks. For the purpose of this study, IOP goal was met if a drop of >20% occurred from baseline initial IOP on or off medical therapy. For all mCPC performed, 37.83% of eyes had met this goal at their most recent post-op visit. For mCPC-naïve patients 40% of eyes met this goal and 35.71% of eyes for repeat mCPC. This proved to be statistically significant in the mCPC-naiive group only (p=0.0425). Subgroup analysis was performed in relation to total J and baseline IOP; neither of these factors proved to be significant in any group in regard to achieving >20% IOP reduction.

Results (cont.): Postoperative complications included IOP elevation of >30% from baseline in 4/37 eyes (10/81%).

Vision loss of 2 lines or more was found in 4/37 patients (10.81%). No patients had significant post-operative inflammation, new macular edema, or hypotony. The number of medications remained the same or increased in all patients after intervention. The average energy was 68.23J in the first-time group vs 80.49 J in the repeat group; this was not found to be significant but did demonstrate a general trend correlating with IOP reduction on linear regression in both groups.

The following variables were not found to be significant in relation to achieving pressure goal: lens status, number of medications, number of prior glaucoma surgeries, or type of glaucoma.

PRESENTERS

ABSTRACTS

Presented by: Lily Kim Hipp, MD Project Mentor: Philip Shands, MD Discussion: The results demonstrate a statistically significant IOP reduction in mCPC-naiive patients at most recent follow up, but no significant IOP reduction for repeat mcPC patients. Possible causes behind this could include the relatively low energy utilized during the procedure; approximately 50%-75% fewer total joules were delivered than in other studies with target outcomes of 20% IOP reduction. The rates of visual acuity and IOPrelated complications were similar to slightly lower than other published complication rates. Longer follow up and larger sample size is needed for both first-time and repeat groups to ameliorate these issues, as well as more research into outcomes of repeat mCPC. Conclusion: Micropulse cyclophotocoagulation is a useful adjunct and modality of treatment for eyes in refractory glaucoma in that the rates of complication are low compared to incisional surgery and continuous-wave CPC. However, up-titration of energy delivered during the procedure may be warranted in the VA population studied, and more research into the efficacy of repeat mCPC is needed.

Contact Information: Lily Kim Hipp, MD Email: Lily.Kim@uhhospitals.org Telephone: 912-704-8521

PRESENTERS

ABSTRACTS

Presented by: Stephen Lau Project Mentor: Yasemin Sozeri, MD Purpose: To compare the safety and efficacy of angle-based implant and non-implant minimally invasive glaucoma surgery (MIGS) in moderate severity open-angle glaucoma with concurrent cataract extraction Methods: A retrospective chart review from January 2010 to February 2022 was conducted on patients having open angle glaucoma with moderate severity (defined as Humphrey visual field mean deviation (MD) between -6 dB and -12 dB) undergoing MIGS with concurrent cataract extraction. Exclusion criteria included prior intraocular surgery and uveitic glaucoma. Baseline demographic and clinical data was collected. Outcomes were assessed such as change in intraocular pressure (IOP), number of drug classes, best-corrected visual acuity (BCVA) and visual field MD, as well as rate of complications and reoperations. The IOP and number of drug classes were evaluated at post-operative day 1 (POD1), week 1 (POW1), month 1 (POM1), month 3, month 6, month 12, month 18 and month 24. Fisher’s exact test, Mann-Whitney test and two-tailed Student’s t-test were used for data analysis.

Results: There were 22 cases of implant MIGS (3 Cypass, 7 Hydrus and 12 iStent implants) and 30 of non-implant MIGS (2 ab interno canaloplasty, 1 gonioscopy assisted transluminal trabeculotomy, (GATT), 6 Kahook Dual Blade (KDB) goniotomy and 21 Trabectome goniotomy). The only statistically significant baseline difference between the groups was a higher number of drug classes in the non-implant group (median 3 (IQR 2-4) vs. 2 (IQR 1-3), p=0.04).

IOP change from baseline was greater in the implant group on POW1 (mean -3.7 ± 3.9 vs. +0.5 ± 5.7 mmHg, p=0.01) and POM1 (median -2.0 (IQR -5.25-0) vs. +1.5 (IQR -4-3) mmHg, p=0.04); the other time points did not show a statistically significant difference in IOP change from baseline between the implant and non-implant groups.

There was no statistically significant difference in the proportion of patients achieving POM12 or POM24 IOP < 18 or < 15 mmHg. There was no statistically significant difference in change in number of drug classes at any time point. There was no statistically significant difference in change in visual field MD or rate of complications. There was a statistically significant greater number of reoperations in the non-implant group (6/30 vs. 0/22, p=0.03).

Discussion: While the efficacy of implant and non-implant MIGS was comparable in terms of IOP or medication reduction, the greater number of reoperations for uncontrolled intraocular pressure in the non-implant group warrants further scrutiny. Of those requiring re-operation, there were 4 Trabectome, 1 KDB and 1 GATT patients requiring 1 selective laser trabeculoplasty (SLT), 4 trabeculectomy with mitomycin C and 1 XEN gel stent implantation. Those requiring reoperation had a statistically significant better baseline BCVA compared to others in the non-implant group (median logMAR 0.20 (IQR 0.10-0.48) vs. 0.47 (IQR 0.30-0.65), p=0.02) and higher proportion with history of prior SLT (67% vs. 17%, p=0.03). Another difference approaching statistical significance was a higher baseline IOP (median 19 (IQR 15-23) vs. 14 (IQR 11-16) mmHg, p=0.10). This suggests preoperative differences in patient selection contributing to a higher risk of MIGS failure and need for reoperation.

Conclusion: There were no statistically significant persistent differences in reduction of IOP or number of drug classes between implant and non-implant MIGS over 2 years of follow up. However, more patients in the nonimplant group required re-operations, mostly undergoing filtering procedures. This may be a result of selection bias and further investigation is warranted.

Contact Information: Stephen Lau, MD Email Address: Stephen.Lau@uhhospitals.org Phone: 347-849-0133

PRESENTERS

ABSTRACTS

Presented by: Archana Murali Project Mentor: Douglas Rhee, MD Purpose: Elevated intraocular pressure is a known risk factor for glaucoma progression. Bimatoprost is a prostaglandin F2 alpha analog that is used to lower intraocular pressure (IOP). This study investigates the effects of bimatoprost free acid (BFA) on human ciliary body smooth muscle (CBSM) cells. In 2009, Yucel et al. described a potential uveolymphatic pathway for drainage of aqueous humor from the anterior chamber of the eye and regulation of IOP. The goal of this study is to further investigate the uveolymphatic pathway and explore if the mechanism of treatment of BFA involves ocular lymphangiogenesis.

Methods: CBSM cells were dissected from the anterior segment of five human donor eyes (ages 62, 70, 73, 74, and 76). The cells were cultured in Dulbecco's Modified Eagle Medium (DMEM). The human donor CBSM cells were treated with five different concentrations of BFA (10 nM, 28.5 nM, 57 nM, 128.5 nM, and 200 nM), solubilized in ethanol for 72 hours, and compared to a vehicle control group treated with 0.001% ethanol solution for 72 hours.

Western blot analysis with ImageJ was used to quantify the expression of the lymphatic markers angiopoietin-1 (ANG-1), angiopoietin-2 (ANG-2), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), neuropilin 2 (NRP2), podoplanin (PDPN), prospero homeobox 1 (PROX-1), and tyrosine kinase with immunoglobulin like and epidermal growth factor like domains 1 (TIE-1) in the human CBSM cells following 72-hour BFA treatment. Foldchange in lymphatic marker expression in the treatment groups as compared to the vehicle control group was calculated and two-tailed paired t-tests with significance set at p < 0.05 were used for statistical analysis.

Results: Compared to the vehicle control, BFA treated human CBSM cells demonstrated on average a 18% increase in LYVE-1 expression at 10 nM (n=5; p=0.021), a 37% increase in TIE-1 expression at 28.5 nM (n=4; p = 0.024), a 22% increase in ANG-1 expression at 28.5 nM (n=5; p=0.027), and a 29% increase in ANG-1 expression at 57 nM BFA (n=5; p=0.049). No statistically significant dose-dependent relationship was observed for PDPN (n=5), ANG-2 (n=5), PROX-1 (n=5), NRP-2 (n=5).

Discussion: This study confirms the expression of lymphatic markers in human CBSM cells. Increases in TIE-1, LYVE-1, and ANG-1 following 72-hour BFA treatment may indicate the development of lymphatics in response to drug treatment. Results also demonstrate a dose-dependent relationship in lymphatic marker expression, with significantly more LYVE-1, TIE-1, and ANG-1 protein expression in cells treated with 10 nM, 28 nM, or 57 nM BFA compared to a non-significant change in protein expression with 128.5 nM and 200 nM BFA. This dose-dependent relationship should be explored further and could have important clinical relevance.

Conclusion: Increase in the expression of these markers following BFA treatment compared to the vehicle control group suggests that lymphangiogenesis could be a therapeutic mechanism by which bimatoprost reduces IOP. Future qPCR studies and ex vivo studies will be performed to further explore the mechanism of treatment of bimatoprost and the role of lymphangiogenesis on IOP reduction.

Contact Information: Archana Murali Email: abm110@case.edu Phone:: 612-877-1204

PRESENTERS

ABSTRACTS

Presented by: Roy Swanson, MD Project Mentor: Manasvee Kapadia, MD Purpose: To assess baseline characteristics and outcomes of laser peripheral iridotomy (LPI) for primary angle closure suspect (PACS) and primary angle closure (PAC) patients at the Cleveland Veterans Affairs Eye Clinic.

Recent studies done in Asian population has shown a low risk of acute angle closure and angle closure glaucoma in PACS and PAC patients. Our goal was to study these outcomes in a totally different patient population in regards to age and race. Our hypothesis was that a significant portion of this group of patients would have narrow angles primarily due to lens changes, and secondly that many of these patients would need cataract surgery regardless of LPI. Methods: This study is a retrospective chart review of patients who have undergone LPI from 2018 to 2020 at the Cleveland VA Eye Clinic. The patients were identified by CPT code for LPI. Inclusion criteria included any patients that were identified as PACS and PAC. Patients with primary angle closure glaucoma and secondary glaucoma were excluded There were 169 eyes that were identified that met these criteria. Pre-procedural eye characteristics and measurements that were analyzed included age, gender, race, refraction, intraocular pressure, lens status, tomography, keratometry, anterior chamber measurements, symptoms related to acute angle closure, episodes of acute angle closure. Post-procedure outcomes and adverse events were also analyzed, including cataract progression, acute angle closure, posterior synechiae, intraocular pressure, hyphema, need to add glaucoma drops, cataract surgery, glaucoma surgery.

Results: LPI was performed in 169 eyes. The mean age of the patients in our study was 68, ranging from 37 to 85.

There were 162 (95.9%) male and 7 (4.1%) female patients. Race distribution was as follows: 140 (82.8%) white, 19 (11.2%) African Americans, 4 (2.4%) Hispanic, 2 (1.2%) Pacific Islander, and 4 (2.4%) other. The post-LPI mean IOP at 1 year was significantly lower than the pre-procedure mean IOP, with a difference of 1.63 mmHg (p<0.05).

Only 2 eyes (1.2%) needed the addition of glaucoma drops. Only 1 eye (0.6%) had acute angle closure after the LPI. 17 eyes (10%) underwent cataract surgery within 3 years after LPI. None of the eyes in the study required glaucoma surgery. 1 eye developed posterior synechiae.

Discussion: A significant portion (10%) of the eyes in our study underwent cataract surgery within 3 years after LPI, therefore performing LPI for these patients may not have been indicated. Overall our results are consistent with the ZAP trial data, which suggested that not all patients need LPI. Our study is unique in that it confirmed these results in a different population, which consisted of an older population and mostly white and African American patients. Future directions for a follow up study would include obtaining biometry measurements including axial length and lens thickness. In another study that analyzed data from the ZAP trial, anterior segment OCT parameters were found to be predictive of progression from PACS to PAC or acute angle closure, therefore anterior segment OCT could also be added to the pre-procedure assessment. Despite the large volume of LPIs that were performed, there were no serious adverse events from LPI. Conclusion: The results of our study supported our hypothesis that a significant portion of the patients that underwent LPI likely had lens induced changes affecting angle morphology and needed cataract surgery within 3 years of LPI. Our study also showed that LPI at the Cleveland VA Eye Clinic was a safe procedure with no serious adverse events and effective at preventing acute angle closure.

Contact Information: Roy Swanson, MD Email: roy.swanson2@uhhospitals.org Phone: 520-456-6657

PRESENTERS

ABSTRACTS

Presented by: Kunal Suri, MD Project Mentor: Loretta Szczotka-Flynn, O.D., PhD Purpose: Recent publications have shown that despite advances in CL materials, the incidence of microbial keratitis has remained stable. This study identified factors associated with severe contact lens-related bacterial keratitis (BK) which drives the morbidity associated with the disease.

Methods: The study enrolled 153 BK cases across 14 sites in the U.S. and the medical records pertaining to treatment of the corneal ulcers were collected and reviewed. Patients completed a questionnaire with questions related to demographics, type of CL used, wearing schedule, lens handling practices, and storage case handling.

Patients with ulcer/infiltrate size >=2 mm in size, or with presence of hypopyon or patients in whom fortified antibiotics were prescribed, were classified as severe keratitis. Univariate and Multivariate analysis of the factors associated with each of the severity parameter individually, as well as severe keratitis as a whole, was performed.

Univariate and multivariate analysis was also performed evaluating the factors associated with presence of positive corneal cultures.

Results: In a univariate analysis, smoking (OR = 1.76; 95% CI 0.82-3.75; p = 0.145) and silicone hydrogel lenses (SH) (OR = 3.76; 95% CI 1.27-11.17, p = 0.017) were associated with ulcer/infiltrate size >= 2mm. Increased age (OR=1.04; 95% CI 1-1.06, p=0.051, smoking (OR = 2.1; 95% CI 0.86-5.12; p = 0.103), SH lenses (OR = 2.94; 95% CI 0.86-10.06, p = 0.086), and sleeping in CL (OR=2.32; CI 0.96-5.63; p=0.062) were associated with presence of hypopyon. None of the factors were associated with significant increase in likelihood of prescribing fortified antibiotics. Smoking (OR=2.47; CI 1-6.13; p=0.050) and SH lenses (OR=2.58; CI 0.98-6.82; P=0.055) were associated with developing severe keratitis. Smoking (OR=2.08; CI 0.94-4.63; p=0.071) was also associated with positive corneal cultures. Daily disposable (DD) CL were associated with decreased risk of developing corneal ulcer >=2 mm or hypopyon, prescription of fortified antibiotics and decreased overall risk of severe keratitis. A multivariable analysis showed that none of the factors were associated with ulcer size > 2mm or increase likelihood of prescribing fortified antibiotics. Sleeping often in lenses showed a trend towards increase in hypopyon formation (p=0.08). Smoking was associated with overall increased risk of developing severe ulcers (p=0.06) and also with positive corneal cultures (p=0.07). The increase in severity with SH lenses or the protective effect of daily disposable lenses was not seen in the multivariate model.

Discussion/Conclusion: Severe disease is responsible for vision loss and morbidity; possible approaches to decrease such morbidity is to address associated modifiable risk factors. Our study showed trends toward increased risk of severe keratitis in patients that smoke (or former smokers), those that wear non-daily disposable lenses, or wear silicone hydrogel lenses in the univariate analysis. The increased risk in smokers was confirmed in the multivariate analysis, however the effect of SH or DD lenses was not seen in the multivariate model. In conclusion, smoking is a modifiable risk factor and counselling regarding smoking cessation is an important step in decreasing the incidence of severe infection and vision loss in CL users.

Contact Information: Kunal Suri, MD Email: Kunal.Suri@uhhospitals.org Phone: 856-448-2259

PRESENTERS

ABSTRACTS

Presented by: Soham Shah Faculty Mentor: Dr. Loretta Szczotka-Flynn, OD, PhD Purpose: The aims of this study are to determine risk factors for contact lens (CL) related microbial keratitis (MK).

Comparing soft CL users that developed MK with high-risk controls that did not present with MK despite exhibiting at least one previously published risky behavior will enable us to understand the relative risk of different factors and determine which factors are the most important when determining susceptibility to CL MK. Methods: The study enrolled 158 high-risk controls at University Hospitals of Cleveland and 153 MK cases across 14 sites in the U.S. Odds ratios were calculated, and univariate logistic regressions and multivariate logistic regression models were developed, examining age, sex, smoker status, and contact lens material. Additionally, the study assessed whether the patient wore daily disposables, wore lenses overnight, showered with lenses, or swam with lenses. Initially, all cases were compared with high-risk controls, and in a secondary analysis, only severe MK patients were compared with the controls; this will better inform patients of the relative risks of factors leading to MK with high morbidity.

Results: In the multivariable analysis comparing all cases with controls, increased age (OR = 1.04; 95% CI 1.021.06; p = 0.000541), male sex (OR = 2.36; 95% CI 1.45-3.85, p = 0.00750), smoking (OR = 11.92; 95% CI 4.1334.45; p = 5.15e-05), and frequent extended lens wear (OR = 3.45; 95% CI 1.89-6.29; p = 0.00245) were found to confer an increased risk of developing microbial keratitis. A multivariable analysis comparing controls with only severe MK cases showed very similar results. Increased age (OR = 1.04; 95% CI 1.02-1.06; p =0.00437), male sex (OR = 2.94; 95% CI 1.72-5.02, p = 0.00179), smoking (OR = 15.2; 95% CI 5.15-44.9; p = 6.09e-06), and frequent extended lens wear (OR = 3.98; 95% CI 2.09-7.56; p = 2.50e-05) were found to confer an increased risk of developing microbial keratitis.

Discussion: Previous studies have assessed behaviors, demographics, or CL types for risk of MK using everyday CL wearers without disease. However, no one has used a cohort of high-risk controls as the comparison arm. Such a control group further displays which demographics, such as older age and male sex, CL patterns, such as extended wear, and behaviors, such as smoking, are attributable to disease burden. This study is also part of a larger genomic study that will detect genetic variants involved in leaving a patient susceptible to MK. Our current focus is investigation of clinical risk factors which will be controlled for and adjusted in the analysis of genetic factors in the near future.

Conclusion: This study supports other studies, confirming that risk factors such as older age, male sex, smoking history, and extended lens wear are associated with a greater likelihood of developing CL-MK

Contact Information: Soham Shah Emaik: sss295@case.edu Phone: 908-938-5066

PRESENTERS

ABSTRACTS

Presented by: Tarek Tabbaa, MD Project Mentor: Warren Sobol, MD Purpose: To report a case series on a single family pedigree with clinically diagnosed Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy (ADNIV) and showcase different facets of this disease process utilizing numerous imaging modalities and genetic testing.

Methods: Multimodal imaging including Ocular Coherence Tomography (OCT), fluorescein angiography, color fundus photographs, and Humphrey visual field (HVF) testing was obtained for all five patients for further characterization and documentation of this inherited retinal disease. Additionally, genetic testing utilizing SPARK therapeutics inherited retinal disease (IRD) panel was conducted on all patients.

Results: Characteristic imaging patterns emerged after analyzing the results of all multimodal imaging modalities and patient examination that seem to correlate with disease severity and highlight the progressive nature of this disease process. Novel genetic markers were also discovered in some patients in this cohort that have not been previously reported in the literature that could serve as a link between different syndromic ophthalmic conditions.

Discussion: While ADNIV is a rare disease that affects a small number of patients globally, the research and therapeutic approaches that can be developed to cure this disease process can be applied to a variety of other disorders. Further scientific inquiry and research in this disease's pathogenesis and treatment can pave the way for better management and understanding of a variety of other uveitic conditions from an inflammatory perspective, as well as a better understanding of common neovascular conditions encountered by ophthalmologists around the world, such as diabetic retinopathy and wet AMD. The increased utility of genetic testing for retinal diseases also aids in discovering future therapeutic targets as the depth and breadth of treatment of retinal diseases continues to evolve. As more cases of rare dystrophies with genetic testing are reported, we speculate that many variants of unknown significant may become better understood and potentially allow for subsequent development of novel gene therapies.

Conclusion: Multimodal imaging in concert with genetic testing are useful methods for testing individuals with inherited retinal diseases for disease progression and to assess efficacy of treatment. Furthermore, increased genetic testing of inherited retinal diseases may reveal novel genetic mutations that may serve as targets for future genetic treatment regimens.

Contact Information: Tarek Tanbaa, MD Email: tarek.tabbaa2@uhhospitals.org Phone: 810-265-1916

PRESENTERS

ABSTRACTS

Presented by: David Shieh, MD Project Mentor: Warren Sobol, MD Purpose: The disease burden of diabetic retinopathy is substantial in the VA population, especially in patients with early-stage disease, and in patients with macular edema that does not respond well to anti-VEGF injections. Prior studies have shown that a low-grade inflammatory process may be involved in the early pathogenesis of diabetic retinopathy. Knockout studies from the Taylor Lab have demonstrated that cytokines including IL-17A, IL-6 and CCL2, not previously associated with a major role in the development of proliferative diabetic retinopathy, may in fact play a more important role in this process.

This study is therefore undertaken to attempt confirmation of these lab findings in human subjects with proliferative diabetic retinopathy.

Methods: VA patients with no diabetes (ND), proliferative diabetic retinopathy (PDR), and proliferative diabetic retinopathy with diabetic macular edema (PDR with DME) were identified and informed consent was obtained.

Blood samples were collected with peripheral venipuncture. Patients undergoing vitrectomy for complications of proliferative diabetic retinopathy, as well as control patients undergoing vitrectomy for other indications, were similarly identified and informed consent was obtained. Vitreous samples were collected during the initial core vitrectomy. The samples were then prepared and analyzed for a panel of cytokines using an ELISA-based microfluidic immunoassay.

Results: A total of 8 vitreous samples and 12 blood samples have been analyzed so far. Of the cytokines assessed in this study, IL-6 and CCL2 were found to be particularly elevated in the blood and vitreous of diabetic patients.

The mean vitreous concentrations of IL-6 were found to be 6.69  5.95, 12.10  0.92, and 18.35  5.16 pg/ml in ND, PDR, and PDR with DME patients respectively. The mean vitreous concentrations of CCL2 were found to be 474.5  105.4, 674.3  25.5, and 1036.5  321.7 pg/ml in ND, PDR, and PDR with DME patients respectively. The preliminary data suggest that vitreous levels of IL-6 and CCL2 are elevated in patients with PDR, especially in those with macular edema, when compared to nondiabetic patients. Similar trends were found in the blood levels of IL-6 and CCL2 in the three groups.

Conclusion: Our preliminary data suggests that there are increased levels of the pro-inflammatory cytokines IL-6 and CCL2 in the blood and vitreous of patients with diabetic retinopathy compared to those without diabetic retinopathy. This supports the findings of prior animal knockout studies and human studies, and may lead to potential future therapeutic targets in early-stage and anti-VEGF-nonresponsive diabetic retinopathy.

Contact Information: David Shieh, MD Email: David.Shieh@uhhospitals.org Phone: 732-261-8875

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Presented by: Blanche L. Kuo, BS Project Mentor: Rishi Singh, MD and Katherine Talcott, MD Purpose: Intravitreal therapy (IVT) with anti-vascular endothelial growth factor (anti-VEGF)is first line treatment for diabetic macular edema (DME). This study describes anti-VEGF IVT frequency and long-term visual outcomes among DME patients in routine clinical practice in the United States Methods: A retrospective analysis was performed among treatment-naïve DME patients (no prior IVT in the past 12 months) initiating anti-VEGF IVT from 1/1/2015-12/31/2019 using de- identified electronic medical records (IRIS® Registry). The change in visual acuity (VA) from baseline and anti-VEGF IVT frequency (average number of injections and intervals) were reported for up to 6 years of follow-up. VA outcomes were further stratified by baseline VA and number of injections (0, 1-2, 3-4, 5-7, 8-10, ≥11) for the given year.

Results: At Year 1, 124,684 eyes received a mean (SD) of 3.9 (2.8) anti-VEGF injections with a mean injection interval of 10.0 (7.9) weeks and gained a mean of +3.2 (16.4) letters. Among patients with 6 years of follow-up, 1,235 eyes received a mean of 2.9 (2.1) injections with a mean interval of 12.3 (8.2) weeks between injections in year 6; and these patients gained a mean of +0.5 (19.7) letters from baseline. Median (interquartile range) follow-up time was 2.1 years (1.22, 3.24). When stratified by baseline VA, overall change in VA was negative for eyes starting with VA ≥20/25 and &lt;20/25 to 20/40, and positive for eyes starting with VA &lt;20/40 to 20/80, &lt;20/80 to &gt;20/200, and ≤20/200 at the end of follow-up (Figure 1). When stratified by the average number of received injections in each year, change in VA from baseline was +2.8 in those who received 1-2 injections compared to +4.8 in those who received ≥11 injections in the first year. This trend was consistent in subsequent years (Figure 2).

Patients receiving 1-2 injections experienced VA loss from baseline ranging from -0.28 to -1.12 across Years 3-6 of follow-up. Patients receiving 3-4 injections experienced VA loss from baseline of -0.53 at Year 6 of follow-up.

Patients receiving 5 or more injections did not experience a loss in VA from baseline.

Discussion: The number of injections decreased, and injection intervals increased year over year up to 6 years regardless of baseline VA. Improvements in BVA were greater in eyes with worse vision compared to those with better vision. Improvements in VA from baseline were greatest in eyes that received 5 or more injections each year.

Limitations of this study include the nature of a retrospective analysis of data from routine clinical practice, which allowed for limited adjustments for confounding variables.

Conclusion: Findings show that long-term visual outcomes in DME are influenced by BVA at the initiation of antiVEGF treatment as well as the number of injections administered. These results will better equip ophthalmologists in their clinical decision making and management of DME patients.

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Presented by: Blanche L. Kuo, BS Project Mentor: Rishi Singh, MD and Katherine Talcott, MD Figure 1. Change in VA over time by baseline VA in each year of follow-up

Figure 2. Change in VA from baseline by number of injections in each year of follow-up

Contact Information: Blanche L. Kuo, BS Email: Blanchek22@gmail.com Phone: 954-651-3714

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Presented by: Lalita Gupta, MD Project Mentor: Mark A. Prendes, MD Purpose: In thyroid eye disease (TED) patients with vision-threatening compressive optic neuropathy, exposure keratopathy, or stable yet disfiguring proptosis, orbital decompression has been used to increase the volume of the orbit reducing pressure on orbital contents and proptosis by removing bone, orbital fat or both. Approved by the U.S. Food and Drug Administration (FDA) in January 2020 for use in patients with active thyroid eye disease, teprotumumab is a monoclonal antibody that targets the insulin-like growth factor 1 receptor (IGF-1R) and leads to improvement in proptosis, diplopia, clinical activity scores (CAS), and extraocular muscle and orbital fat volume.1-3 While the advent of teprotumumab may suggest that the number of decompressions performed by orbital surgeons would decrease, a change in practice patterns since the approval of this new medication has not been studied or proven. In this study, we aimed to compare rates of orbital decompression for thyroid eye disease before and after the approval of teprotumumab.

Methods: A multi-centered retrospective review of patients with TED cared for by two ASOPRS-trained orbital surgeons at two academic centers was performed with institutional review board approval. The primary outcome, the rate of orbital decompressions, was determined by dividing the number of patients who underwent orbital decompression for TED by the number of patients with TED seen during that time period. Other endpoints included the indication, laterality, and technique for decompression, teprotumumab use, and pretreatment CAS scores. A modified chi-square test was used to compare the decompression rates before and after January 1, 2020 with p<0.05 considered significant.

Results: A total of 743 patients with TED were cared for during the reviewed period from June 2012 to December 2021. Decompressions were performed on 197 orbits (116 patients) by removing either the medial wall and floor (81.7%), lateral wall (2.5%), only floor (14.7%) or only fat (1%). The overall rate of orbital decompressions among The mean CAS score (+/- SD) of patients who underwent decompression was overall 2.63 (+/-1.05) and went from 2.66 (+/- 0.85) to 2.5 (+/- 1.68) after January 1, 2020. The percent of patients who underwent decompression who had a preoperative CAS score of 4 or more increased from 19.1% to 40.9%. The proportion of decompressions that were performed for compressive optic neuropathy, as opposed to exposure keratopathy, decreased from 56.4% to 26.5%. Of the TED patients seen after January 1, 2020, 10.3% (24/234) received teprotumumab. Three (12.5%) of these patients had undergone orbital decompression for compressive optic neuropathy after January 1, 2020.

Discussion/Conclusion: The overall rate of orbital decompressions in the current study decreased as teprotumumab emerged after its FDA approval in January 2020. Orbital decompression continues to play an important role in the management of TED patients especially in cases of compressive optic neuropathy. Further research is needed in the future as the use of teprotumumab expands.

Contact Information: Lalita Gupta, MD Email: Lalita.Gupta@uhhospitals.org Phone: 916-425-5740

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Presented by: Benjamin Kambiz Ghiam, MD Project Mentor: Faruk H. Örge, MD Purpose: To assess short and long-term functional outcomes after frontalis suspension using expanded PolyTetraFluoroEthylene (ePTFE) sling for congenital ptosis repair.

Methods: A retrospective, observational case review was conducted on pediatric patients who underwent frontalis suspension using ePTFE sling from 2008 through 2020. Functional success was assessed by lid height, lid symmetry, and parental satisfaction with the cosmetic outcome. Clinical course and long term functional outcomes after surgery were assessed.

Results: 21 cases met inclusion criteria and were assessed. The follow-up time ranged from 13 months to 11 years (mean 6 years). Functional success after one surgery was 62% at early and late postoperative periods. 6 of 21 cases (29%) required revisional surgery in the early post-operative period due to undercorrection. 3 cases (14%) were complicated by infection and/or granuloma formation. There were no cases of ptosis recurrence in the longterm if success was seen in the early postoperative period.

Conclusion: ePTFE slings remain an excellent option for severe congenital ptosis repair with frontalis sling, demonstrating long-term functional success, with satisfactory lid symmetry and acceptable cosmetic outcome. This is of important consideration in patients younger than 3 years of age, where autogenous materials may not be recommended. The need for early revisional surgery for undercorrection is not uncommon. The current authors also demonstrate a low but considerable risk for infection and/or granuloma formation.

Contact Information: Benjamin Khambiz Ghiam, MD Email: Benjamin.Ghiam@uhhospitals.org

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Presented by: Andrew Pasquale, MD Project Mentor: Mark A. Prendes Purpose: To develop a model to diagnose orbital tumors using imaging characteristics.

Methods: The project is divided into two parts. Firstly, a deep learning algorithm is developed with the purpose to classify orbital lesions using numerous preoperative imaging characteristics and some patient demographics. Probability discrimination capacity will be the main goal of our model. The model, which can be delivered to medical professionals as an application, will use a complex flow chart that will classify the tumor. The second part of the project will be to test the model’s performance by retroactively reviewing patients with orbital tumors whose diagnosis is already known. The final model’s performance will then be tested by its positive predictive value.

Results: How accurately the model predicted the diagnosis of the orbital lesion will be reviewed in the second stage of the project.

Conclusion: Deep learning algorithms, mainly using specific CT and MRI characteristics, may be able to accurately classify or narrow down a differential diagnosis for an orbital lesion

Contact Information: Andrew Pasquale, MD Email: Andrew.Pasquale@uhhospitals.org

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Presented by: Richard Helms, MD PhD Project Mentor: Michael Abrams, MD Purpose: To demonstrate that implanted rare-earth magnets might be used to replicate the forces generated by the medial rectus muscle during normal globe rotations.

Methods: We assume a single magnet under the insertion of the medial rectus muscle, and one or more magnets implanted along the medial orbital wall. A target function was established based on the published force-generation curve for the medial rectus (1). The precise location and strength of each magnet were optimized using a genetic algorithm to maximize agreement between the force-generation curve of our model and the target function while minimizing radial force on the globe. A dipole approximation was used throughout the calculations. Parameter values were constrained based on the dimensions of a hypothetical adult orbit and globe and the strength of N52 rare-earth magnets.

Results: Our optimized magnet configuration approximated the desired medial rectus forces within a range of (+/-) 30 degrees of primary gaze. The tangential forces (abduction/adduction) on the globe remained within 10g of the target force-generation function. The radial force (away from the center of the globe) was less than 20g throughout this range.

Discussion: This simulation shows that rare-earth magnets can be implanted into the orbit to restore an extended range of binocular vision. As a proof-of-principle, we have made simplifying assumptions about the dynamics of this system. We have used a simplified model of the magnetic fields and we have constrained the motion of the globe to rotations about its center. Future work is underway to simulate a more fully dynamic model including orbital elastic forces and more accurate magnetic field calculations.

Conclusion: Transposition procedures provide a constant force against which an unopposed antagonist muscle can operate but do not replicate the varying forces generated the medial rectus muscle during normal rotations, limiting the potential field of single binocular vision. Our model suggests rare-earth magnets might be used to replicate those forces, potentially allowing for an expanded field of SBV. These findings may be relevant to other forms of 'paralytic' strabismus.

Contact Information: Richard Helms, MD, PHD Email: Richard.Helms@Uhhospitals.org Phone: 615-557-6572

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Ö Presented by: John Wang, MD Project Mentor: Faruk Örge , MD Purpose: Horizontal muscle strabismus surgery planning usually involves consulting historic tables that relates preoperative deviation in Prism Diopters with amount of surgery performed to each muscle in millimeters (recession, resection and plication). Any coexisting oblique muscle dysfunction seen in the clinic (in this case inferior oblique (IO)), that is deemed to be significantly affecting the eye versions, is typically addressed during the same surgery. Although inferior oblique muscles are primarily an “elevator” they also function as an abductor and incyclotorter of the eye, weakening procedures to the IO may affect the horizontal alignment. Many surgeons consider altering amount of surgery performed on the horizontal muscles when oblique muscle surgery is also planned. This study assesses the need of adding this correction factor in a patient cohort who has exotropia with inferior oblique over-actions.

Methods: A retrospective review of 1851 patients who underwent strabismus surgery was performed between the time period 01/2008 and 12/2021 here at University Hospital Rainbow Baby Children Hospital. In this group, there were 653 patients with a preoperative diagnosis of exotropia. Among these, there were 387 patients underwent either bilateral lateral rectus recession (BLRc) or BLRc with bilateral inferior oblique myectomy (BIOM). Surgeries were performed by four different primary surgeons in the department of ophthalmology. Exclusion criteria include history of strabismus surgery, presence of vertical deviation, and unequal recession amounts between eyes. A preliminary set of 60 patients were selected for the study, and their surgical outcomes were reviewed.

Results: The mean age was 10.76 years with a range of 9 months to 64.34 years. There were 49 pediatric patients and 11 adult patients. Out of a total of 60 patients, 42 underwent BLRc and 18 underwent BLRc with BIOM. The average preoperative deviation of BLRc patients was 41.04 prism diopters (PD) of exotropia, while it was 34.00 PD of exotropia in the combined BLRc+BIOM group. The average postoperative deviation of BLRc patients was 0.14 PD of exotropia, while it was 2.44 PD of exotropia in the combined BLRc+BIOM group. The mean postoperative evaluation exam was 190.05 days after surgery for the BLRc patients and 92.65 days after surgery for BLRc+BIOM group.

Discussion/Conclusion: This preliminary data of surgical outcomes in patients who underwent BLRc or BLRc+BIOM shows that operating on the oblique muscles does not significantly change the postoperative deviation, suggesting that a correction factor may not be needed when planning for combined BLRc+BIOM.

Contact Information: John Wang, MD Email: John.Wang3@uhhospitals.org Phone: 585-690-6199

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Presented by: Zeina Salem, MD Project Mentor: Faruk Örge , MD Purpose: Horizontal muscle strabismus surgery planning usually involves consulting historic tables that relate preoperative deviation in Prism Diopters with amount of surgery performed to each muscle in millimeters (recession, resection and plication). These tables were built using a retrospective analysis of dose-response curves for correcting deviations in the primary position of gaze. Our study aims to test the accuracy of the most commonly utilized table from Marshal Parks. Our study is a retrospective review and analysis of outcomes of standardized strabismus surgeries performed for correction of esotropia.

Methods: A retrospective review of 678 patients who underwent strabismus surgery for esotropia was performed between the time period 01/2008 and 12/2016 here at University Hospital Rainbow Baby Children Hospital. Among these, 371 patients underwent bilateral medial rectus recession (BMRc) surgery, 92 patients underwent bilateral lateral rectus resection (BLRs), and 57 underwent a medial rectus recession/lateral rectus resection (R&R) surgery.

All surgeries were performed by the same primary surgeon at the same institution, using the same surgical technique and abiding by the amount of recession recommended by the surgical tables. We excluded patients with history of strabismus surgery, who received procedures other than bilateral medial rectus recession and with significant medical conditions altering fusion (cerebral palsy, down syndrome, etc). A preliminary set of 69 patients were selected for the study, and their surgical outcomes were reviewed.

Results: The mean age was 5.27 years with a range of 8 months to 17 years. The female to male ratio was 1:3.3.

The average millimeters of bilateral medial rectus recession performed was 4.86 mm. Of our 69 patients, 63 (91.3%) exhibited postoperative success defined by orthotropia, only phoria, esotropia of ≤10 prism diopters (PD) or exotropia of ≤10 PD at the primary position. Five patients (7.25%) exhibited undercorrection – defined as esotropia of >10PD – and only one patient (1.45%) exhibited overcorrection – defined as exotropia of >10PD. The average preoperative deviation of our group was 36.7 PD of esotropia. And the average postoperative deviation was 8.8 PD of esotropia, and 25 PD of exotropia.

Discussion/Conclusion: This preliminary data of surgical outcomes in patients who underwent BMRc for esotropia shows that the currently used surgical planning tables provide a postoperative success rate and therefore accuracy of 91.3%, which is above the previous published data . We do not see a trend that would require table modification for our surgeries. Additional analysis of data with a larger number of patients may further confirm or adjust these preliminary results, and may provide a corrected correlation of the current table values.

Contact Information: Zeina Salem, MD Email: Zeina.Salem@uhhospitals.org Phone: 904-304-8899

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