Andrea Lora Kossler, MD, FACS, is Associate Professor of Ophthalmology at Stanford University School of Medicine, Director of the Oculofacial Plastic, Reconstructive Surgery, and Co-Director of the Orbital and Ocular Oncology Service at the Byers Eye Institute at Stanford. Dr. Kossler specializes in thyroid eye disease, orbital oncology, and aesthetic oculoplastic surgery. Andrea customizes treatment to each patient’s surgery goals and has developed a reputation as a “top doctor” in oculoplastic patient care. Andrea has been in practice for over 11 years and treats adults and children with oculoplastic and conditions.

Dr. Kossler is an expert in thyroid eye disease and orbital surgery and the Co-Director of the Thyroid Eye Disease Center at Stanford University and an expert in orbital surgery. Andrea’s research interests include the proteomic evaluation of inflammatory ocular surface and orbital diseases, modulation of neural reflexes via neurotization and neurostimulation, evaluating targeted therapies for cutaneous and orbital malignancy, and advancing therapies for thyroid eye disease. Dr. Kossler has authored over 100 publications, abstracts and book chapters and is a national and international speaker on oculofacial plastic and orbital surgery.

Andrea earned her medical degree from Georgetown University School of Medicine where she graduated summa cum laude and valedictorian of her class. She holds a Bachelor of Science degree from the University of Florida where she graduated with highest honors. She completed her internship in internal medicine at the Mount Sinai Medical Center and her residency in Ophthalmology at the number one ranked Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine. She continued at the Bascom Palmer Eye Institute to complete a fellowship in Ophthalmic Plastic and Reconstructive surgery and served as a Clinic Instructor of Ophthalmology.

Outside of work Andrea enjoys time with her husband, two daughters and dog Roxy.

Clinical Focus

  • Ophthalmic Reconstructive & Facial Plastic Surgery
  • Orbital Oncology
  • Thyroid Eye Disease
  • Cosmetic Surgery & Treatments
  • Mohs Reconstruction & Eyelid Surgery
  • Pediatric Oculoplastics
  • Facial nerve palsy
  • Blepharoplasty
  • Eyelid surgery & reconstruction
  • Ptosis repair
  • Oculoplastic Surgery
  • Lacrimal & Tear Duct Surgery
  • Ophthalmic Plastic and Reconstructive Surgery

Academic Appointments

Administrative Appointments

  • Co-Director, Orbital and Ocular Oncology Clinic (2015 - Present)
  • Director, Ophthalmic Plastic, Reconstructive Surgery & Orbital Oncology (2012 - Present)
  • Director, Oculoplastic Cosmetic Surgery & Treatments (2013 - Present)
  • Co-Director, Thyroid Eye Disease Center (2012 - Present)

Honors & Awards

  • Gabilan Fellowship Award, Stanford Office of Faculty Development, Diversity and Engagement (2023)
  • ASOPRS Foundation Research Award, American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) (2023)
  • Emerging Leader National Award, Women in Ophthalmology (2022)
  • Award of Excellence, Aesthetic Surgery Journal (2022)
  • Achievement Award, American Academy of Ophthalmology (AAAO) (2021)
  • Top Doctors Award, Castle Connolly (2021-current)
  • Outstanding Contribution Award, American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) (2020)
  • Gerhard Cless Ophthalmology Lecture Award, Illinois Eye and Ear Infirmary (2020)
  • Hispanic Center of Excellence Award, Stanford School of Medicine (2018)
  • Gabilan Award, Stanford University (2023)
  • National Mentorship Award, Women In Ophthalmology (2017)
  • McCormick & Gabilan Research Award, Stanford School of Medicine (2016)
  • ASOPRS Research Award, American Society of Ophthalmic Plastic & Reconstructive Surgery (ASOPRS) (2015)
  • Best Poster Award, American Academy of Ophthalmology (2014)
  • Top Notch Award, Department of Defense United States Navy (2014)
  • Marvin Quickert Thesis Award, American Society of Ophthalmic Plastic & Reconstructive Surgery (ASOPRS) (2013)
  • Best Ocular & Orbital Oncology Paper AAO Annual Conference, American Academy of Ophthalmology (AAO) (2012)
  • Kober Award, Georgetown School of Medicine (2006)
  • Frank G. Standaert Award, Department of Pharmacology, Georgetown University (2006)
  • Valedictorian, summa cum laude, Georgetown School of Medicine (2006)
  • Milton Corn, MD Award, Georgeown School of Medicine (2005)

Boards, Advisory Committees, Professional Organizations

  • Board of Directors, Women in Ophthalmology (2023 - Present)
  • Executive Board, LATINOUS (2023 - Present)
  • Executive Board, North American Society of Academic Orbital Surgeons (2023 - Present)
  • Member Program Committee, Women in Ophthalmology (2017 - Present)
  • Mentorship Program Chair, American Society of Ophthalmic Plastic & Reconstructive Surgery (ASOPRS) (2016 - Present)
  • Fellow, American Society of Ophthalmic Plastic & Reconstructive Surgery (ASOPRS) (2010 - Present)
  • Member, Women in Ophthalmology (2010 - Present)
  • Member, Association for Research in Vision and (2006 - Present)
  • Member, American Academy of Ophthalmology Association (AAO) (2006 - Present)
  • Member, Alpha Omega Alpha Honorary Medical Society (2005 - Present)
  • Member, American Medical Association (AMA (2002 - Present)

Professional Education

  • Fellowship: Bascom Palmer Eye Institute (2012) FL
  • Residency: Bascom Palmer Eye Institute (2010) FL
  • Medical Education: Georgetown University Internal Medicine Residency (2006) DC
  • Member, American Society of Ophthalmic Plastic and Reconstructive Surgeons, Ophthalmic Reconstructive and Facial Plastic Surgery (2014)
  • Board Certification: American Board of Ophthalmology, Ophthalmology (2012)
  • Board Certification, American Board of Ophthalmology, Ophthalmology (2012)
  • Fellowship, Bascom Palmer Eye Institute, University of Miami, Ophthalmic Plastic, Reconstructive Surgery & Orbital Oncology (2012)
  • Internship: Mount Sinai Med Ctr/ Miami Bch (2007) FL

Research Interests

  • Diversity and Identity
  • Technology and Education

Current Research and Scholarly Interests

Thyroid Eye Disease
Adenoid Cystic Carcinoma of the Lacrimal Gland
Lacrimal Gland Stimulation for the Treatment of Dry Eyes
Orbital Tumors
Floppy Eyelid Syndrome and Obstructive Sleep Apnea

Clinical Trials

  • A Phase 2b, Study of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED) Recruiting

    The overall objective is to study the safety, pharmacokinetics and efficacy of linsitinib (a small molecule IGF-1R inhibitor) administered orally twice daily (BID) vs. placebo, at 24 weeks in the treatment of subjects with active, moderate to severe thyroid eye disease (TED).

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  • A Safety, Tolerability and Efficacy Study of VRDN 001 in Healthy Volunteers and Persons With Thyroid Eye Disease (TED) Recruiting

    Please note that Phase 1/2 (HV & MAD) cohort - recruitment is completed and Phase 3 Component (THRIVE) - is actively recruiting. The investigational drug, VRDN-001, is a monoclonal antibody that inhibits the activity of a cell surface receptor called insulin-like growth factor-1 receptor (IGF-1R). Inhibition of IGF-1R may help to reduce the inflammation and associated tissue swelling that occurs in patients with thyroid eye disease (TED). This clinical trial will evaluate the safety, tolerability and pharmacokinetics (the concentration of drug in the blood over time) of VRDN-001 in healthy volunteers and in patients with TED. Study participants with TED will also be evaluated over time for changes in their signs and symptoms of TED compared to their baseline measurements.

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  • TEPEZZA® (Teprotumumab-trbw) Post-Marketing Requirement Study Recruiting

    This is a double-masked, randomized, parallel-assignment, multicenter trial examining the safety and tolerability of teprotumumab in the treatment of Thyroid Eye Disease (TED) in adult participants. This international, Phase 3b/4 trial is being conducted to fulfill an FDA post-marketing requirement for a descriptive trial to evaluate the safety, efficacy and need for re-treatment of 3 different teprotumumab treatment durations for TED. In addition, serum samples from participants with a Baseline Clinical Activity Score (CAS) ≥3 will be evaluated for biomarkers of disease.

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  • Surgical Idiopathic Intracranial Hypertension Treatment Trial Not Recruiting

    Randomized trial of adults (≥18 years old) with idiopathic intracranial hypertension and moderate to severe visual loss without substantial recent treatment who are randomly assigned to (1) medical therapy, (2) medical therapy plus ONSF, or (3) medical therapy plus VPS. The primary outcome is visual field mean deviation change at first of Month 6 (26 weeks) or time of treatment failure of the eligible eye(s), followed by a continuation study to assess time to treatment failure. The determination of eligible eye(s) is based on meeting the eligibility criteria at baseline.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mariana Nunez, 650-497-7846.

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  • The Secondary Beneficial Effects of Prostaglandin Analog Treatment in Thyroid Eye Disease Patients. Not Recruiting

    The purpose of this study is to evaluate the potential secondary beneficial effect of prostaglandin analogues (PA) treatment in thyroid eye disease (TED) patients. This study aims to determine if PA would change the course of the orbitopathy in TED patients by altering the progression of the common features of TED, including fatty hypertrophy, proptosis, eyelid retraction and optic nerve compression. The eyes with thyroid eye disease and elevated intraocular pressure will be randomised to the PA treatment and the other eye will serve as a control eye and will be treated with Timolol.

    Stanford is currently not accepting patients for this trial. For more information, please contact Barbara Bartlett, 650-724-9259.

    View full details

2023-24 Courses

Stanford Advisees

Graduate and Fellowship Programs

  • Oncology (Fellowship Program)

All Publications

  • An Analysis of Solicitations from Predatory Journals in Ophthalmology. American journal of ophthalmology Justin, G. A., Huang, C., Nguyen, M. K., Lee, J., Seddon, I., Wesley, T. A., Bakri, S. J., Campbell, J. P., Cavuoto, K., Collins, M., Gedde, S. J., Kossler, A. L., Milman, T., Shukla, A., Sridhar, J., Syed, Z. A., Williams, B. K., Woreta, F. A., Patel, S. N., Yonekawa, Y. 2024


    To evaluate trends associated with email communication from potentially predatory publishers to faculty in ophthalmology.Cross sectional study METHODS: Ophthalmologists (n=14) from various subspecialties and institutions were recruited to participate. Participants identified unsolicited emails they had received originating from publishers in May 2021. Information collected included details on email contents and publisher organizations. Trends in communications from predatory publishers were evaluated.Over a 30-day study period, a total of 1813 emails were received from 383 unique publishers and 696 unique journals with a mean (SD) of 4.73 (2.46) emails received per day per participant. Of the 1813 emails identified, 242 (13%) emails were invitations to conferences, whereas 1440 (80%) were solicitations for article submissions to open-access pay-to-publish journals. A total of 522 (29.0%) emails were related to ophthalmology, and reference to a prior publication of the participant occurred in 262 emails (14%). Of the 696 unique journals identified, 174 (25%) journals were indexed on PubMed and 426 (61%) were listed on Beall's list. When comparing journals listed on PubMed versus those that were not, PubMed indexed journals had a higher impact factor (2.1 vs 1.5, p=0.002), were less likely to use "greetings" (76% vs 91%, p<0.001), had fewer spelling/grammar errors (40% vs 51%, p=0.01), and were less likely to offer rapid publication (16% vs 25%, p=0.02).Unsolicited requests to publish occur frequently and may diminish the quality of the scientific literature. We encourage individuals in ophthalmology to be aware of these trends in predatory publishing.

    View details for DOI 10.1016/j.ajo.2024.02.030

    View details for PubMedID 38490339

  • Association of ocular manifestations of Marfan syndrome with cardiovascular complications. American journal of ophthalmology Tran, E. M., Wai, K. M., Kossler, A. L., Mruthyunjaya, P., Rahimy, E., Koo, E. B. 2024


    To evaluate associations between ocular manifestations of Marfan syndrome and cardiovascular complications.retrospective cohort study METHODS: Setting: TriNetX Analytics platform, a federated health research network of aggregated deidentified electronic health record data of over 119 million patients.Patients diagnosed with Marfan syndrome.Univariate logistic regression models were used to evaluate the association of ocular manifestations of Marfan syndrome (such as retinal tears/detachment, lens dislocation, and myopia), with cardiovascular comorbidities. Additional sensitivity analyses were performed using propensity matching.Odds ratio and 95% confidence intervals for incidence of cardiovascular comorbidities (including aortic dissection, valvular disease, and arrhythmias) following diagnosis of Marfan syndrome.19,105 patients were identified that were diagnosed with Marfan disease without ocular manifestations, and an additional 3,887 Marfan patients with ocular comorbidities. Patients who were diagnosed with ocular disease included 883 with ectopic lens, 417 with retinal tear or detachment, 683 with aphakia, 534 with pseudophakia, and 2,465 with myopia. Patients with any ocular manifestations of Marfan were significantly more likely to be diagnosed with all cardiovascular comorbidities modeled including aortic aneurysm and dissection (OR=2.035; p=<0.0001), mitral valve prolapse (OR=2.725; p= p=<0.0001), tricuspid valve disorders (OR=2.142; p=<0.0001), cardiac arrhythmias (OR=1.836; p=<0.0001), and all cardiovascular outcomes combined (OR=2.194; p=<0.0001).In a large and diverse cohort of patients with Marfan syndrome, ocular manifestations of the disorder appear strongly associated with cardiovascular comorbidities.

    View details for DOI 10.1016/j.ajo.2024.02.023

    View details for PubMedID 38403098

  • Reply. Ophthalmology Shah, S. A., Amarikwa, L., Sears, C. M., Clauss, K. D., Rajjoub, R. D., Kang, J. Y., Tamhankar, M. A., Briceño, C. A., Harrison, A. R., Cockerham, K. P., Wester, S. T., Douglas, R. S., Dosiou, C., Kossler, A. L. 2024

    View details for DOI 10.1016/j.ophtha.2024.01.003

    View details for PubMedID 38349298

  • Anatomic and Surgical Considerations in the Management of a Sellar and Suprasellar Arachnoid Cyst: 2-Dimensional Operative Video. Operative neurosurgery (Hagerstown, Md.) Rychen, J., Constanzo, F., Chan, D., Kossler, A. L., Fernandez-Miranda, J. C. 2024

    View details for DOI 10.1227/ons.0000000000001061

    View details for PubMedID 38198191

  • Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease. Ophthalmic plastic and reconstructive surgery Men, C. J., Amarikwa, L., Pham, B., Sears, C., Clauss, K., Lee, B. W., Lee, W. W., Pasol, J., Ugradar, S., Shinder, R., Cockerham, K., Wester, S., Douglas, R., Kossler, A. L. 2023


    Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED.This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated.Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss.Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.

    View details for DOI 10.1097/IOP.0000000000002564

    View details for PubMedID 37972960

  • Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multi-Center Study. Ophthalmology Shah, S. A., Amarikwa, L., Sears, C. M., Clauss, K. D., Rajjoub, R. D., Kang, J. Y., Tamhankar, M. A., Briceño, C. A., Harrison, A. R., Dosiou, C. C., Cockerham, K. P., Wester, S. T., Douglas, R. S., Kossler, A. L. 2023


    To assess the duration, incidence, reversibility, and severity of adverse events (AEs) in patients with thyroid eye disease (TED) treated with teprotumumab.Multi-center retrospective observational cohort study.Patients with TED of all stages and activity levels treated with at least 4 infusions of teprotumumab.Patients were treated with teprotumumab between February 2020 and October 2022 at 6 tertiary centers. AE metrics were solicited and recorded at each visit. AEs were grouped according to the United States FDA Adverse Event Reporting System.Primary outcomes measure: AE incidence and onset.AE severity, reversibility, duration, proptosis response, clinical activity score (CAS) reduction, and Gorman diplopia score (GDS) improvement.The study evaluated 131 patients. Proptosis improved by 2mm or more in 77% (101/131) of patients with 3.0±2.1mm average proptosis improvement and 3.2 points average CAS reduction. GDS improved by at least one point for 50% (36/72) of patients with baseline diplopia. AEs occurred in 81.7% (107/131) of patients. Patients had a median of 4 AEs. Most patients' AEs were mild (74.0%, 97/131), 28.2% (37/131) moderate, and 8.4% (11/131) severe. Mean interval AE onset was 7.9 weeks after the first infusion. Resolved AEs had a mean duration of 17.6 weeks. Forty-six percent (60/131) of patients had at least 1 persistent AE at last follow-up. Patients had a mean follow-up of 70.2±38.5 weeks after the first infusion. The most common type of AEs was musculoskeletal (58.0%, 76/131), followed by gastrointestinal (38.2%, 50/131), skin (38.2%, 50/131), ear and labyrinth (30.5%, 40/131), nervous system (20.6%, 27/131), metabolic (15.3%, 20/131), and reproductive system (12.2%, 16/131). Sixteen patients (12.2%) discontinued therapy due to AEs, including hearing loss (n=4), inflammatory bowel disease flare (n=2), hyperglycemia (n=1), muscle spasms (n=1), and multiple AEs (n=8).AEs are commonly reported while receiving teprotumumab treatment. Most are mild and reversible; however, serious AEs can occur and may warrant treatment cessation. Treating physicians should inform patients about the AE risk, properly screen patients prior to treatment, monitor patients closely throughout therapy, and understand how to manage AEs should they develop.

    View details for DOI 10.1016/j.ophtha.2023.10.018

    View details for PubMedID 37852417

  • Accuracy of Digital Image Analysis for Diagnosing IgG4 Related Ophthalmic Disease Charoenkijkajorn, C., Gill, H., Glory, B., Shi, W., Homer, N., Men, C., Kossler, A., Wu, A., Lin, J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023
  • Automated Detection of Dysthyroid Optic Neuropathy in Graves' Ophthalmopathy with Computed Tomography (CT) Scans by Convolutional Neural Networks Hung, J., Luo, A., Deng, Y., Chung, C., Fuh, C., Perera, C., Myung, D., Kossler, A., Liao, S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023
  • Characteristics of Predatory Publishing Solicitation in Ophthalmology Nguyen, M., Huang, C., Lee, J., Seddon, I., Bakri, S., Syed, Z., Woreta, F., Shukla, A., Cavuoto, K., Collins, M., Williams, B., Kossler, A., Campbell, J., Patel, S., Justin, G., Yonekawa, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023
  • The use of Google Trends and Twitter data as a tool for evaluating public interest in hyaluronic acid eyelid filler. Journal of clinical and translational research Cohen, S. A., Kossler, A. L. 2023; 9 (2): 76-83


    Google Trends and the Twitter Academic Research Product Tract (TARPT) are free, online tools that can be used to evaluate public interest in plastic surgery procedures.The aim of the study was to evaluate the correlation between online public interest in hyaluronic acid eyelid filler on two popular web platforms (Google and Twitter) and hyaluronic acid filler procedure volumes in the United States.The Google Trends database and the TARPT tool were used to calculate the number of annual Google searches and Twitter tweets, respectively, related to 10 search terms associated with hyaluronic acid eyelid filler injections from January 2010 to December 2020. Annual procedure volumes for hyaluronic acid filler injections were obtained from the American Society of Plastic Surgery (ASPS). Univariate linear regression was used to correlate Google searches to ASPS procedure volumes and Twitter tweet volumes to ASPS procedure volumes.Significant positive correlations were found between Google Trends data and ASPS procedure volumes for 8/10 search terms and between Twitter tweet volumes and ASPS procedure volumes for 6/10 search terms, respectively. Online public interest in eyelid filler related search terms increased significantly over time according to an exponential model (P < 0.0001).We observed statistically significant positive associations between public interest related to eyelid filler on two online platforms, Google and Twitter, and hyaluronic acid soft-tissue filler procedure volumes. The Google Trends and TARPT databases represent free information sources for surgeons that may be used to inform marketing and advertising decisions and to anticipate patient inquiries during the patient encounter.Information provided by the Google Trends and TARPT tools can be used by surgeons to (1) inform marketing and advertising strategies and (2) gain insight into which procedures patients are researching during a given time period, preparing them to best address the evolving needs of patients.

    View details for PubMedID 37034000

    View details for PubMedCentralID PMC10075089

  • Preparing the Ocular Surface for a Boston Keratoprosthesis Type 1 Through En Bloc Minor Salivary Gland Transplantation and Mucous Membrane Grafting in End-Stage Stevens-Johnson Syndrome. Cornea Arboleda, A., Phansalkar, R., Amescua, G., Lee, W. S., Brandt, J. D., Mannis, M. J., Kossler, A. L., Lin, C. C. 2023


    This case describes the successful visual restoration of a patient with end-stage Stevens-Johnson syndrome (SJS) with a severely keratinized ocular surface.This study is a case report.A 67-year-old man with SJS secondary to allopurinol sought visual rehabilitation options. His ocular surface was severely compromised from sequelae of chronic SJS, leaving him with light perception vision bilaterally. The left eye was completely keratinized with severe ankyloblepharon. The right eye had failed penetrating keratoplasty, limbal stem cell deficiency, and a keratinized ocular surface. The patient declined both a Boston type 2 keratoprosthesis and a modified osteo-odonto keratoprosthesis. Therefore, a staged approach was pursued with (1) systemic methotrexate to control ocular surface inflammation, (2) minor salivary gland transplant to increase ocular surface lubrication, (3) lid margin mucous membrane graft to reduce keratinization, and finally, (4) Boston type 1 keratoprosthesis for visual restoration. After minor salivary gland transplant and mucous membrane graft, the Schirmer score improved from 0 mm to 3 mm with improvement in ocular surface keratinization. This approach successfully restored the vision to 20/60, and the patient has retained the keratoprosthesis for over 2 years.Sight restoration options are limited in patients with end-stage SJS with a keratinized ocular surface, aqueous and mucin deficiency, corneal opacification, and limbal stem cell deficiency. This case demonstrates successful ocular surface rehabilitation and vision restoration in such a patient through a multifaceted approach that resulted in successful implantation and retention of a Boston type 1 keratoprosthesis.

    View details for DOI 10.1097/ICO.0000000000003262

    View details for PubMedID 37159138

  • Transcutaneous retrobulbar amphotericin B for rhino-orbital-cerebral mucormycosis: a multi-center retrospective comparative study. Orbit (Amsterdam, Netherlands) Dallalzadeh, L. O., Ediriwickrema, L. S., Fung, S. E., Men, C. J., Kossler, A. L., Kupcha, A. C., Mawn, L. A., Burkat, C. N., van Landingham, S. W., Conger, J. R., Simmons, B., Pham, C., Akella, S. S., Setabutr, P., Ho, T., Couch, S. M., Kim, J. S., Demirci, H., Korn, B. S., Kikkawa, D. O., Liu, C. Y. 2023: 1-8


    PURPOSE: To assess whether transcutaneous retrobulbar amphotericin B injections (TRAMB) reduce exenteration rate without increasing mortality in rhino-orbital-cerebral mucormycosis (ROCM).METHODS: In this retrospective case-control study, 46 patients (51 eyes) with biopsy-proven ROCM were evaluated at 9 tertiary care institutions from 1998 to 2021. Patients were stratified by radiographic evidence of local orbital versus extensive involvement at presentation. Extensive involvement was defined by MRI or CT evidence of abnormal or loss of contrast enhancement of the orbital apex with or without cavernous sinus, bilateral orbital, or intracranial extension. Cases (+TRAMB) received TRAMB as adjunctive therapy while controls (-TRAMB) did not. Patient survival, globe survival, and vision/motility loss were compared between +TRAMB and -TRAMB groups. A generalized linear mixed effects model including demographic and clinical covariates was used to evaluate the impact of TRAMB on orbital exenteration and disease-specific mortality.RESULTS: Among eyes with local orbital involvement, exenteration was significantly lower in the +TRAMB group (1/8) versus -TRAMB (8/14) (p=0.04). No significant difference in mortality was observed between the ±TRAMB groups. Among eyes with extensive involvement, there was no significant difference in exenteration or mortality rates between the ±TRAMB groups. Across all eyes, the number of TRAMB injections correlated with a statistically significant decreased rate of exenteration (p=0.048); there was no correlation with mortality.CONCLUSIONS: Patients with ROCM with local orbital involvement treated with adjunctive TRAMB demonstrated a lower exenteration rate and no increased risk of mortality. For extensive involvement, adjunctive TRAMB does not improve or worsen these outcomes.

    View details for DOI 10.1080/01676830.2023.2186435

    View details for PubMedID 36880205

  • Reduction of Teprotumumab-Induced Hearing Loss With Comparable Efficacy Using Half-Dose Therapy. Ophthalmic plastic and reconstructive surgery Phansalkar, R., Lu, T., Alyono, J., Lee, J., Dosiou, C., Kossler, A. L. 2023


    Teprotumumab has been shown to be effective in the treatment of thyroid eye disease, a potentially vision-threatening condition. Adverse events, including sensorineural hearing loss, have been associated with teprotumumab. The authors present the case of a 64-year-old female who discontinued teprotumumab due to significant sensorineural hearing loss after 4 infusions, along with other adverse events. The patient was unresponsive to a subsequent course of intravenous methylprednisolone and orbital radiation, during which she experienced worsening thyroid eye disease symptoms. Teprotumumab was restarted 1 year later, at a half dose of 10mg/kg for 8 infusions. Three months post-treatment, she retains resolution of double vision and orbital inflammatory signs, and significant improvement in proptosis. She tolerated all infusions with an overall reduction in the severity of her adverse events and without return of significant sensorineural hearing loss. The authors conclude that a lower dose of teprotumumab can be effective for patients with active moderate-severe thyroid eye disease who experience significant or intolerable adverse events.

    View details for DOI 10.1097/IOP.0000000000002355

    View details for PubMedID 36877549

  • Oral Corticosteroids for Teprotumumab-Related Hearing Loss: A Case Report. Case reports in ophthalmology Lu, T. J., Amarikwa, L., Winn, B. J., Inserra, M., Dosiou, C., Kossler, A. L. 2023; 14 (1): 134-139


    Teprotumumab is a novel insulin-like growth factor-1 receptor inhibitor approved for the treatment of thyroid eye disease, but growing reports of hearing loss require further investigation. To date, an effective protocol for managing hearing loss in this setting has not been determined. Here, we present the first report of the resolution of teprotumumab-related hearing loss with prompt oral prednisone. A 70-year-old woman on teprotumumab experienced sudden hearing loss and tinnitus after her first infusion. An audiogram demonstrated a mild down-sloping to moderately severe mixed conductive and sensorineural hearing loss that was promptly treated with prednisone 60 mg for 6 days with a 1-week gradual taper. An audiogram 3 weeks later demonstrated return of hearing to normal thresholds, and the whole teprotumumab treatment course was completed without further issue. This case highlights the importance of audiometric monitoring, prompt identification of hearing symptoms, and the potential for oral steroids to reverse teprotumumab-related hearing loss.

    View details for DOI 10.1159/000529422

    View details for PubMedID 37034380

  • The Readability and Accountability of Online Patient Education Materials Related to Common Oculoplastics Diagnoses and Treatments. Seminars in ophthalmology Cohen, S. A., Tijerina, J. D., Kossler, A. 2022: 1-7


    To assess the readability and accountability of online patient education materials related to oculoplastic diagnoses and treatments, and to determine the source of information encountered by patients searches.We conducted a Google search for 20 search terms related to common oculoplastic diagnoses and treatments and analyzed the first 10 patient education websites populated for each term. Readability was assessed using four validated measures: Gunning Fog Index, Flesch-Kincaid Grade Level, Simple Measure of Gobbledygook, and New Dale-Chall Readability. Accountability was assessed using 4 JAMA benchmarks on a scale of 0-4, with one point awarded for each of the following accountability criteria provided on the website: (1) including all authors and their relevant credentials (2) listing references (3) providing disclosures and (4) providing date of last update.The average grade level of 200 websites analyzed was 10.89, with 29% written at less than the 6th grade reading level recommended by the American Medical Association. The source of online information was most frequently educational institutions (36%) and private practices (34%), with fewer online patient education materials from national organizations (18%) and crowdsourced websites (12%). There were no significant differences in readability when comparing searches related to oculoplastics diagnoses versus treatments. Websites averaged 0.91 out of a maximum of 4 recommended accountability criteria, reflecting low overall accountability.Online education resources encountered by patients are often written at inappropriate reading levels and demonstrate low accountability. Online patient education materials are most frequently maintained by educational institutions and private practices, with fewer articles from national organizations. Revision of online materials may be necessary to improve health literacy among oculoplastic patients.

    View details for DOI 10.1080/08820538.2022.2158039

    View details for PubMedID 36524760

  • Teprotumumab-related hyperglycemia. The Journal of clinical endocrinology and metabolism Amarikwa, L., Mohamed, A., Kim, S. H., Kossler, A. L., Dosiou, C. 2022


    CONTEXT: Graves orbitopathy (GO) or thyroid eye disease is a potentially sight-threatening and disfiguring autoimmune disease. Teprotumumab is a monoclonal antibody against the insulin-like growth factor-I receptor that was recently approved for GO treatment. Hyperglycemia is a recognized adverse event of teprotumumab, occurring in 10% of patients in two recent randomized controlled trials.OBJECTIVE: Our study aimed to report the incidence, severity, management, and longitudinal glycemic changes in patients treated with teprotumumab in an academic practice cohort.METHODS: This longitudinal, observational study included all consecutive patients treated with teprotumumab between March 2020 and May 2022 at one institution. Hemoglobin A1c was measured every 3-months.RESULTS: Forty-two patients with baseline normoglycemia (n=22), pre-diabetes (n=10), and diabetes (n=10) were followed for a mean of 47.5 weeks. Overall, HbA1c increased by 0.5% at 3-months. Least-square mean changes in HbA1c at 3 months were 1.3 (p<0.001), 0.7 (p=0.01), and 0.1 (p=0.41) in patients with diabetes, pre-diabetes, and normoglycemia, respectively. Twenty-two patients (52%) had hyperglycemia which was graded as mild, moderate, and life-threatening in 55%(12/22), 41%(9/22), and 5%(1/22) of cases, respectively. Age, pre-existing diabetes, and Hispanic and Asian race/ethnicity were significant risk factors for hyperglycemia. Among patients with hyperglycemia, 36.4% (8/22) returned to baseline glycemic status at last follow-up.CONCLUSIONS: While effective, teprotumumab carries a significant risk of hyperglycemia, especially in patients with diabetes. Hyperglycemia may persist after stopping teprotumumab. These findings underscore the importance of guidelines for screening and management of teprotumumab-related hyperglycemia.

    View details for DOI 10.1210/clinem/dgac627

    View details for PubMedID 36300333

  • New onset or deterioration of thyroid eye disease after mRNA SARS-CoV-2 vaccines:report of 2 cases and literature review. The Journal of clinical endocrinology and metabolism Mohamed, A., Tzoulis, P., Kossler, A. L., Dosiou, C. 2022


    CONTEXT: Occurrence of Graves' disease (GD) has been reported following SARS-CoV-2 vaccine administration, but little is known about thyroid eye disease (TED) after SARS-CoV-2 vaccination.METHODS: We report two cases of TED activation following SARS-CoV-2 vaccination: one case of TED worsening in a patient with GD, and one of de novo active TED progressing to dysthyroid optic neuropathy in a patient with a history of Hashimoto's hypothyroidism. Our literature search revealed 8 additional reported TED cases associated with SARS-CoV-2 vaccination until June 2022. We review the characteristics, duration and management of TED following SARS-CoV-2 vaccination in these cases.RESULTS: Of all 10 reported TED cases following SARS-CoV-2 vaccination, four cases developed new onset TED and 6 cases with prior stable TED experienced significant deterioration. Six patients had known Graves' disease and 2 patients had Hashimoto's thyroiditis. Two cases progressed to dysthyroid optic neuropathy, 6 had moderate/severe active disease and 2 cases had mild disease that did not require treatment. Seven TED cases received teprotumumab and had a favorable response, two of which had prior limited response to initial prednisone or methylprednisolone and tocilizumab therapy.CONCLUSIONS: New diagnosis or deterioration of TED after mRNA SARS-CoV-2 vaccination can occur, with most cases described in patients with underlying autoimmune thyroid disease. Our report raises awareness to this potential complication to promote early recognition and prompt management of TED associated with mRNA SARS-CoV-2 vaccines. Further studies are needed to explore the mechanism of TED following mRNA SARS-CoV-2 vaccination, risk factors, prevention and treatment.

    View details for DOI 10.1210/clinem/dgac606

    View details for PubMedID 36251747

  • Trends in Leadership and Award Recognition Among Women in the American Society of Retina Specialists JOURNAL OF VITREORETINAL DISEASES Reeves, M. R., Pasricha, M., Ludwig, C. A., Chandramohan, A., Azad, A. D., Li, A. S., Rosenblatt, T. R., Sears, C., Kossler, A. L., Do, D., Pan, C. K. 2022; 6 (5): 374-380
  • Teprotumumab and the Evolving Therapeutic Landscape in Thyroid Eye Disease JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Kossler, A., Douglas, R., Dosiou, C. 2022; 107: S36-S46
  • Teprotumumab and the Evolving Therapeutic Landscape in Thyroid Eye Disease. The Journal of clinical endocrinology and metabolism Kossler, A. L., Douglas, R., Dosiou, C. 2022; 107 (Supplement_1): S36-S46


    Thyroid eye disease (TED) is a sight-threatening and debilitating autoimmune condition, with limited therapies available, that often poses diagnostic and therapeutic challenges. In recent years, the treatment landscape has shifted to early intervention with targeted therapy.A PubMed review of the literature was conducted for the period between 1979 and 2021. Search terms included thyroid eye disease, teprotumumab, targeted therapy, Graves disease, Graves ophthalmopathy, dysthyroid optic neuropathy, and related terms in different combinations. Novel biologic therapies for TED have emerged as alternatives to traditional steroid regimens in recent years. New insights into TED pathophysiology have uncovered the role of the insulin-like growth factor 1 receptor (IGF-1R) and led to the development of teprotumumab, an IGF-1R-inhibiting monoclonal antibody.Randomized clinical trials demonstrating the efficacy of teprotumumab for TED led to Food and Drug Administration approval. Teprotumumab is gradually replacing immunosuppressive agents as first-line therapy in the United States for active moderate-to-severe TED, while emerging reports also show its use in other stages of the disease. Recent data highlight risk factors for adverse events and screening protocols to maximize patient safety. Personalized therapeutic plans developed through effective partnership between endocrinologists and ophthalmologists aim to enhance the safety and outcomes of TED treatments and improve care for this complex disease.TED management is shifting to an era of targeted therapy with multidisciplinary care. Teprotumumab has demonstrated superior efficacy to conventional treatments and has transformed our therapeutic and surgical algorithms. Clinical guidelines and additional studies are needed to further guide and refine therapy.

    View details for DOI 10.1210/clinem/dgac168

    View details for PubMedID 36346685

  • Trends in Leadership and Award Recognition Among Women in the American Society of Retina Specialists. Journal of vitreoretinal diseases Reeves, M. R., Pasricha, M. V., Ludwig, C. A., Chandramohan, A., Azad, A. D., Li, A. S., Rosenblatt, T. R., Sears, C. M., Kossler, A. L., Do, D. V., Pan, C. K. 2022; 6 (5): 374-380


    This work evaluates trends in achievement of women in the retina field, through an analysis of gender representation in the American Society of Retina Specialists (ASRS).This retrospective, longitudinal study spans 1983 to 2020. Historical data classified by male or female gender were collected from ASRS's overall membership, board of directors and officers, and recipients of the 4 society awards. The proportion of each benchmark held by women was compared with prior decades since the founding of ASRS using the Fisher's exact test.Women's representation increased from 11% of ASRS members in 2007 to 19.7% in 2020. From 2010 to 2019, women received a higher proportion of society awards (21.1%) compared with membership prior to the start of that decade. In 2020, women were proportionally well represented in board of director positions (21.9%) and held a significantly higher proportion of board positions than in the period 1983 to 1989 (P = .02). From 1983 to 2020, women held 4.3% (1 of 23) of presidencies.Although the number of women in retina is increasing, women remain underrepresented in the leadership of ASRS. Interventions to increase exposure to female mentorship and improve childcare benefits are warranted to engage female ophthalmology trainees in retina and ultimately society leadership.

    View details for DOI 10.1177/24741264211021019

    View details for PubMedID 37006904

    View details for PubMedCentralID PMC9954927

  • Erdheim-Chester disease and vemurafenib: a review of ophthalmic presentations and clinical outcomes. Orbit (Amsterdam, Netherlands) Park, J. K., Huang, L. C., Kossler, A. L. 2022: 1-12


    PURPOSE: To provide a comprehensive review of ocular and orbital manifestations of Erdheim-Chester Disease (ECD) and compare clinical outcomes with vemurafenib (INN) to historical treatments (HT). Primary outcomes are ophthalmic findings on presentation, changes in visual acuity, and mortality rate. Secondary outcomes include the progression of ocular findings, systemic involvements, and treatment modalities.METHODS: All published literature from January 1983 to March 2021 was searched for ophthalmic manifestations of ECD. Clinical outcomes following HT were collected and compared with INN.RESULTS: Forty-seven patients with ECD and ophthalmic presentations were identified. The mean age was 49.6years (SD=15.0). Proptosis (65.6%) and extraocular muscle restrictions (42.5%) were the most common presenting signs. Of 41 (87.2%) patients with orbital masses on radiologic examination, 90.2% were bilateral, and 53.7% were located in the intraconal space. Ophthalmic examination was significant for xanthelasma (27.2%), optic disc edema (34.0%), and subretinal changes (21.3%). Common treatments were systemic steroids (76.6%), interferon-alpha (17.0%), and cyclophosphamide (14.9%). INN was less commonly used (12.8%). The mean change in logMAR visual acuity declined with HT (29.9%) but improved with INN (79.1%) (p>0.05). The proportion of eyes with complete vision loss increased after HT (p<0.05). The overall mortality rate was 27.7% and notably higher in the HT group (29.3%) when compared to the INN group (16.7%) (p>0.05).CONCLUSION: ECD presents with many ophthalmic manifestations. Although the intraocular treatments remain controversial, INN should be highly considered in treating orbital ECD patients with BRAF-V600E mutations to prevent and reverse vision loss.

    View details for DOI 10.1080/01676830.2022.2087232

    View details for PubMedID 35702885

  • #CosmeticsTwitter: Predicting Public Interest in Nonsurgical Cosmetic Procedures Using Twitter Data. Aesthetic surgery journal Cohen, S. A., Tijerina, J. D., Shah, S. A., Amarikwa, L., Kossler, A. L. 2022


    The use of social media in plastic surgery is expanding. The Twitter Academic Research Product Tract (TARPT) database provides plastic surgeons the opportunity to monitor public interest in plastic surgery procedures. Previously, TARPT has been shown to be effective in tracking public interest in surgical cosmetic facial and body procedures.To determine the ability of the TARPT tool to track and predict public interest in nonsurgical cosmetic procedures and to examine temporal public interest trends in nonsurgical cosmetic procedures.We used the TARPT tool to calculate the total number of tweets containing keywords related to 15 nonsurgical cosmetic procedures from 2010 to 2020. We obtained annual case volumes for each of the 15 procedures from annual reports provided by the American Society of Plastic Surgeons (ASPS). We used univariate linear regression to compare tweet volumes and procedure volumes, using P < 0.05 as a threshold for significance.Univariate linear regression revealed significant positive correlations between tweet volumes and ASPS procedure volumes for 10 search terms representing six nonsurgical cosmetic procedures: "xeomin", "microdermabrasion", "facial filler", "fat filler", "fat injections", "fat transfer", "hyaluronic acid filler", "hyaluronic acid injection", "HA filler", and "PRP filler". Thirty-two search terms did not demonstrate a significant relationship, illustrating the importance of careful selection of search terms.Our analyses demonstrates that the TARPT tool is an informative data source for plastic surgeons, with the potential to (1) guide marketing and advertising strategies and (2) monitor real-time public interest in nonsurgical cosmetic procedures, helping surgeons respond to patients' evolving needs.

    View details for DOI 10.1093/asj/sjac147

    View details for PubMedID 35675468

  • Primary central nervous system amyloidoma involving cranial nerves V and VII: A case report and literature review INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT Son, E., Mohyeldin, A., Men, C., Pendharkar, A., Fernandez-Miranda, J. C., Kossler, A. L. 2022; 28
  • A Pilot Study on Novel Ptotic Eye Dataset: Automated Prediction of Horizontal Corneal Diameter on Digital Photos of Taiwanese Ptotic Patients by Convolutional Neural Networks (CNNs) Hung, J., Chen, K., Chandrashan, P., Myung, D., Kossler, A., Fuh, C., Liao, S., Hsu, C. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Automatic Blepharoptosis Measurement by Iris Edge Detection with a Deep Learning Model Chen, K., Chandrashan, P., Chiu, H., Kossler, A., David, M., Fuh, C., Hsu, C., Tseng, M., Liao, S., Hung, J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Gender Disparities in the American Association for Pediatric Ophthalmology and Strabismus Rosenblatt, T., Azad, A. D., Kossler, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Teprotumumab-related hearing loss treated with oral corticosteroids Amarikwa, L., Lu, T., Inserra, M., Winn, B., Dosiou, C., Kossler, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Long-term real world teprotumumab outcomes Lu, T., Bair, H., Amarikwa, L., Diniz, S., Singh, P., Clauss, K., Dosiou, C., Wester, S., Rootman, D., Kossler, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Comparison of treatment cost and quality-of-life impact of thyroid eye disease therapies Shah, S., Lu, T., Yu, M., Hiniker, S., Dosiou, C., Kossler, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Advances in the Treatment of Thyroid Eye Disease Associated Extraocular Muscle Myopathy and Optic Neuropathy. Current neurology and neuroscience reports Lu, T. J., Amarikwa, L., Sears, C. M., Kossler, A. L. 2022


    PURPOSE OF REVIEW: To review emerging treatments for thyroid eye disease (TED) associated extraocular muscle myopathy and dysthyroid optic neuropathy (DON).RECENT FINDINGS: Emerging targeted biologic therapies may alter the disease course in TED. Teprotumumab, a type I insulin-like growth factor receptor inhibitor, is the most recent addition to the treatments available for TED-associated extraocular muscle myopathy causing diplopia. Small studies also suggest a potential therapeutic benefit for DON. Various recent studies have also expanded our knowledge on conventional TED therapies. The therapeutic landscape of TED and its sequelae has evolved in recent years. New targeted therapies have the potential to reduce the extraocular muscle and orbital volume expansion which can lead to diplopia and vision loss from optic nerve compression. Longer term efficacy and durability data is needed to determine the role biologics, such as teprotumumab, should play in the treatment of TED patients compared to the current standard of care.

    View details for DOI 10.1007/s11910-022-01194-7

    View details for PubMedID 35614367

  • Representation of Women in Ophthalmology Subspecialty Societies over 20 OPHTHALMOLOGY Azad, A. D., Chandramohan, A., Li, A. S., Rosenblatt, T. R., Reeves, M. R., Veerappan-Pasricha, M., Ludwig, C. A., Nguyen, A., Winges, K. M., Wang, S. Y., Pan, C. K., Moss, H. E., Do, D. V., Fountain, T. R., Kossler, A. L. 2022; 129 (5): 587-590
  • Comparison between 7 Tesla and 3 Tesla MRI for characterizing orbital lesions. Diagnostic and interventional imaging Lecler, A., Duron, L., Charlson, E., Kolseth, C., Kossler, A. L., Wintermark, M., Moulin, K., Rutt, B. 2022


    PURPOSE: Characterizing orbital lesions remains challenging with imaging. The purpose of this study was to compare 3 Tesla (T) to 7 T magnetic resonance imaging (MRI) for characterizing orbital lesions.MATERIALS AND METHODS: This prospective single-center study enrolled participants presenting with orbital lesions from May to October 2019, who underwent both 7 T and 3 T MRI examinations. Two neuroradiologists, blinded to all data, read both datasets independently and randomly. They assessed general characteristics of each orbital lesion as well as image quality and presence of artifacts. Comparison between both datasets was made using Fisher exact test.RESULTS: Seven patients (4 women, 3 men) with a median age of 52 years were enrolled. Orbital lesion conspicuity was better scored at 7 T compared to 3 T MRI, with 3/7 lesions (43%) scored as very conspicuous at 7 T compared to 0/7 lesion (0%) at 3 T, although the difference was not significant (P=0.16). Delineation of lesion margins was better scored at 7 T compared to 3 T with 3/7 lesions (43%) scored as very well delineated on 7 T compared to 0/7 lesions (0%) at 3 T, although the difference was not significant (P=0.34). Details of internal structure were better assessed at 7 T compared to 3 T, with 4/7 lesions (57%) displaying numerous internal details compared to 0/7 lesions (0%) at 3 T (P=0.10). Internal microvessels were visible in 3/7 lesions (43%) at 7 T compared to 0/7 lesions (0%) at 3 T (P=0.19).CONCLUSION: Although no significant differences were found between 7 T and 3 T MRI, assumably due to a limited number of patients, our study suggests that 7 Tesla MRI might help improve the characterization of orbital lesions. However, further studies with more patients are needed.

    View details for DOI 10.1016/j.diii.2022.03.007

    View details for PubMedID 35410799

  • Expert Consensus on the Use of Teprotumumab for the Management of Thyroid Eye Disease Using a Modified-Delphi Approach. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Douglas, R. S., Kossler, A. L., Abrams, J., Briceno, C. A., Gay, D., Harrison, A., Lee, M., Nguyen, J., Joseph, S. S., Schlachter, D., Tan, J., Lynch, J., Oliver, L., Perry, R., Ugradar, S. 2022


    BACKGROUND: Teprotumumab is the first treatment for thyroid eye disease (TED), a debilitating autoinflammatory condition, approved by the Food and Drug Administration in the United States, which reduces proptosis and improves quality of life. In the absence of guidelines, clinical recommendations were developed for using teprotumumab in patients with TED in the United States.METHODS: A 3-round modified-Delphi panel was conducted between October 2020 and February 2021 with experts in the management of patients with TED. Key areas regarding the use of teprotumumab were investigated, including eligible patient populations, concomitant treatments, and assessment of response and adverse events. This used 2 survey rounds via an online questionnaire, where statements were scored using 9-point Likert scales. Statements with conflict were included in the third round, involving a consensus meeting via videoconference.RESULTS: Consensus was obtained for all statements (n = 75); of which, 56% were revised to enable agreement of the group. The consensus meeting provided agreement regarding which populations should receive teprotumumab therapy, including all adult patients with TED with a clinical activity score of ≥4. Treatment with teprotumumab can also be considered for TED patients displaying the following characteristics: a CAS of <3, lid retraction of ≥2, and mild or early optic neuropathy with close clinical observation. Further recommendations included suitability of treatment for those beyond 16 months following the initial diagnosis of TED, low CAS concomitant treatment with steroids in some cases, retreatment for those who have relapses, and finally a recommendation to continue therapy for all 8 infusions despite the lack of response by the fourth infusion.CONCLUSIONS: This work constitutes the first consensus on guidelines for the use of teprotumumab. The modified Delphi approach involved physicians with significant experience with the clinical use of teprotumumab, and recommendations were based on current evidence.

    View details for DOI 10.1097/WNO.0000000000001560

    View details for PubMedID 35421877

  • A Paradigm Shift in the Management of Thyroid Eye Disease How Teprotumumab Has Changed the Therapeutic Interface. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Ugradar, S., Kossler, A. L., Douglas, R., Cockerham, K. 2022; 42 (1): 26-34


    Teprotumumab, a monoclonal antibody that blocks the insulin-like growth factor-1 receptor, has recently been approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED). Since its approval, aside from data on the safety and clinical efficacy of teprotumumab from Phase-2 and Phase-3 trials, only a handful of reports have been published regarding its use in the wider population. In this review, we briefly describe the mechanism of action of teprotumumab and review the literature to provide an overview of published clinical experience. This information was used to provide recommendations for patient selection, management of patient expectations, infusion details and site options, tips to optimize the authorization process, and how to monitor and mitigate side effects.A systemic review of the literature was performed regarding teprotumumab, focusing on its mechanisms of action and published reports on its use on patients with TED. A review of Embase, Medline (PubMed), Web of Science, and Google Scholar was conducted.Clinical experience following the approval of teprotumumab has confirmed its efficacy in reducing inflammation and proptosis in patients with acute TED (<2 years). The reduction in proptosis occurs due to a reduction in orbital fat and muscle volume. Furthermore, there is evidence for its use in patients with compressive optic neuropathy. There are also reports that show its efficacy in reducing proptosis, inflammation, and diplopia in patients with chronic TED (>2 years). Teprotumumab was associated with side effects, such as muscle spasm, hearing loss, and hyperglycemia. To date, 2 case reports have shown a possible association with flares of inflammatory bowel disease.Teprotumumab is a powerful therapeutic option for the treatment of TED. Clinical experience following FDA approval has demonstrated efficacy in treating patients with acute and chronic TED. It is the only therapeutic option that has been shown to reduce orbital soft tissue expansion in TED. However, it is expensive, and sometimes, obtaining insurance authorization can be time consuming and difficult. Further work will reveal its full side effect profile and help to establish its role in the armamentarium used to treat TED.

    View details for DOI 10.1097/WNO.0000000000001515

    View details for PubMedID 35500236

  • A Paradigm Shift in the Management of Thyroid Eye Disease How Teprotumumab Has Changed the Therapeutic Interface JOURNAL OF NEURO-OPHTHALMOLOGY Ugradar, S., Kossler, A. L., Douglas, R., Cockerham, K. 2022; 42 (1): 26-34
  • Hearing Dysfunction After Treatment with Teprotumumab for Thyroid Eye Disease. American journal of ophthalmology Sears, C. M., Azad, A. D., Amarikwa, L., Pham, B. H., Men, C. J., Kaplan, D. N., Liu, J., Hoffman, A. R., Swanson, A., Alyono, J., Lee, J. Y., Dosiou, C., Kossler, A. L. 2022


    PURPOSE: To characterize the frequency, severity and resolution of hearing dysfunction in patients treated with teprotumumab for thyroid eye disease (TED).DESIGN: Prospective observational case series.METHODS: Ophthalmic examination and adverse event assessment, including otologic symptoms, were performed at baseline, after infusions 2, 4, and 8, and at 6-month follow-up in consecutive patients who received at least 4 teprotumumab infusions. Labs were collected at baseline and during treatment. Audiometry, patulous Eustachian tube (PET) testing and otolaryngology evaluation were obtained for patients with new or worsening otologic symptoms, with a subset obtaining baseline and post-treatment testing.RESULTS: Twenty-seven patients were analyzed (24 females, 3 males, average 56.3-years-old). Twenty-two patients (81.5%) developed new subjective otologic symptoms, after a mean of 3.8 infusions (SD 1.8). At 39.2 week average follow-up after the last infusion, most patients with tinnitus (100%), ear plugging/fullness (90.9%), and autophony (83.3%) experienced symptom resolution, while only 45.5% (5 of 11) of patients with subjective hearing loss/decreased word comprehension experienced resolution. Six patients underwent baseline and post-treatment audiometry, 5 of whom developed teprotumumab-related sensorineural hearing loss (SNHL) and one patient also developed PET. Three of the 5 patients with teprotumumab-related SNHL had persistent subjective hearing loss at last follow-up. A prior history of hearing loss was discovered as a risk factor for teprotumumab-related SNHL (p=0.008).CONCLUSIONS: Hearing loss is a concerning adverse event of teprotumumab and its mechanism and reversibility should be further studied. Until risk factors for hearing loss are better understood, we recommend baseline audiometry with PET testing and repeat testing if new otologic symptoms develop. Screening, monitoring and prevention guidelines are needed.

    View details for DOI 10.1016/j.ajo.2022.02.015

    View details for PubMedID 35227694

  • An Outperforming Artificial Intelligence Model to Identify Referable Blepharoptosis for General Practitioners. Journal of personalized medicine Hung, J., Chen, K., Perera, C., Chiu, H., Hsu, C., Myung, D., Luo, A., Fuh, C., Liao, S., Kossler, A. L. 2022; 12 (2)


    The aim of this study is to develop an AI model that accurately identifies referable blepharoptosis automatically and to compare the AI model's performance to a group of non-ophthalmic physicians. In total, 1000 retrospective single-eye images from tertiary oculoplastic clinics were labeled by three oculoplastic surgeons as having either ptosis, including true and pseudoptosis, or a healthy eyelid. A convolutional neural network (CNN) was trained for binary classification. The same dataset was used in testing three non-ophthalmic physicians. The CNN model achieved a sensitivity of 92% and a specificity of 88%, compared with the non-ophthalmic physician group, which achieved a mean sensitivity of 72% and a mean specificity of 82.67%. The AI model showed better performance than the non-ophthalmic physician group in identifying referable blepharoptosis, including true and pseudoptosis, correctly. Therefore, artificial intelligence-aided tools have the potential to assist in the diagnosis and referral of blepharoptosis for general practitioners.

    View details for DOI 10.3390/jpm12020283

    View details for PubMedID 35207771

  • Modified Gundersen Flap Using Inferior Palpebral-Bulbar Conjunctiva. Cornea Mekonnen, B., Kossler, A. L., Lin, C. C. 1800; 41 (2): 260-263


    PURPOSE: The purpose of this article was to describe a modification to the traditional Gundersen flap technique that expands eligible eyes to include those with severe conjunctival scarring and to report results from a clinical case.METHODS: A 68-year-old woman with a history of herpes simplex keratitis, multiple failed penetrating keratoplasties, lagophthalmos, persistent epithelial defect, and low visual potential in the left eye presented for the evaluation of a Gundersen flap. Severe superior bulbar conjunctival scarring precluded a traditional approach. A modified Gundersen flap technique using a contiguous flap of inferior palpebral-bulbar conjunctiva extending from the inferior tarsal border to the limbus was devised and performed.RESULTS: The modified Gundersen flap technique successfully stabilized the ocular surface, obviating the need for a cosmetically disfiguring permanent tarsorrhaphy or an evisceration.CONCLUSIONS: This modified Gundersen flap technique expands the indications to eyes with severe conjunctival scarring and can be offered in eyes with previous trabeculectomies, glaucoma drainage implants, and scleral buckles, which were previously excluded from the globe-preserving option.

    View details for DOI 10.1097/ICO.0000000000002823

    View details for PubMedID 35037907

  • #PlasticsTwitter: The Use of Twitter Data s a Tool for Evaluating Public Interest in Cosmetic Surgery Procedures. Aesthetic surgery journal Cohen, S. A., Tijerina, J. D., Amarikwa, L., Men, C., Kossler, A. 1800


    BACKGROUND: Plastic surgeons are increasingly turning to social media to market their services. The newly released Twitter Academic Research Product Track (TARPT) database provides free, customizable analysis of keywords that are included in tweets on the Twitter platform. The TARPT tool may provide valuable insight into public interest in cosmetic surgery procedures.OBJECTIVES: To determine TARPT's utility in tracking and predicting public interest in cosmetic surgery procedures and to examine temporal trends in tweets related to cosmetic facial and body procedures.METHODS: The TARPT tool was used to calculate total number of tweets containing keywords related to 10 facial cosmetic procedures and 7 cosmetic body procedures from 2010 to 2020. Annual volumes for respective procedures were obtained from annual statistics reports of the American Society of Plastic Surgeons (ASPS) from 2010 to 2020. Univariate linear regression was used to compare tweet volumes and procedure volumes, taking P < 0.05 as the cutoff for significance.RESULTS: Variations in tweet volume were observed. Univariate linear regression analysis demonstrated statistically significant positive correlations between tweet volumes and ASPS procedure volumes for 7 search terms: "eyelid lift", "facelift", "lip injections", "mastopexy", "butt lift", "butt implants", and "liposuction". Many procedure-related keywords were not significant, demonstrating the importance of careful selection of Twitter search terms.CONCLUSIONS: The TARPT database represents a promising novel source of information for plastic surgeons, which the potential to inform marketing and advertising decisions for emerging trends in plastic surgery interest before these patterns become apparent in surgical or clinical volumes.

    View details for DOI 10.1093/asj/sjab429

    View details for PubMedID 34962572

  • Representation of Women in Ophthalmology Subspecialty Societies over 20 Years. Ophthalmology Azad, A. D., Chandramohan, A., Li, A. S., Rosenblatt, T. R., Reeves, M. R., Pasricha, M. V., Ludwig, C. A., Nguyen, A., Winges, K. M., Wang, S. Y., Pan, C. K., Moss, H. E., Do, D. V., Fountain, T. R., Kossler, A. L. 1800


    The representation of women has increased over the last 20 years among ophthalmology subspecialty society new membership, award winners, and executive committee membership; however, proportional representation is still lacking at most benchmarks.

    View details for DOI 10.1016/j.ophtha.2021.12.011

    View details for PubMedID 34958831

  • Infusion Center Guidelines for Teprotumumab Infusions: Informed Consent, Safety, and Management of Side Effects. Journal of infusion nursing : the official publication of the Infusion Nurses Society Kang, J., Lechuga, M., Braun, J., Kossler, A., Douglas, R., Cockerham, K. 2021; 44 (6): 331-338


    Teprotumumab was the first and only medication approved by the US Food and Drug Administration for the treatment of thyroid eye disease in January 2020. Thyroid eye disease is a complex autoimmune inflammatory disease that can be sight-threatening, debilitating, and disfiguring to affected patients. Although biologic therapies are a preferred treatment option for many complex immunologic and oncologic conditions, their use in ophthalmology and endocrinology may be more novel. The goals of this article are to introduce this new therapeutic option; discuss its mechanism of action, indications for use, administration protocol, infusion precautions, and informed consent; and review common side effects and management.

    View details for DOI 10.1097/NAN.0000000000000446

    View details for PubMedID 34753152

  • Corneal Neurotization via Dual Nerve Autografting. Ophthalmic plastic and reconstructive surgery Charlson, E. S., Pepper, J. P., Kossler, A. L. 2021


    Corneal neurotization is a fast-evolving surgical procedure for sensory reinnervation in neurotrophic keratopathy. After neurotization, prior reports document return of corneal sensation on average 8 months after surgery with 38mm of sensation gain measured via cochet bonnet esthesiometer testing. Here, the authors describe a dual nerve grafting approach via simultaneous parallel sural nerve grafts from both the supratrochelar and supraorbital nerves to the affected contralateral cornea with return of sensation by postoperative week 11.

    View details for DOI 10.1097/IOP.0000000000002064

    View details for PubMedID 34652308

  • Early efficacy of teprotumumab for the treatment of dysthyroid optic neuropathy: A multicenter study. American journal of ophthalmology case reports Sears, C. M., Wang, Y., Bailey, L. A., Turbin, R., Subramanian, P. S., Douglas, R., Cockerham, K., Kossler, A. L. 2021; 23: 101111


    Purpose: To study post-interventional findings in patients with dysthyroid optic neuropathy (DON) treated with teprotumumab.Observations: In this multicenter observational Case series, patients with DON were treated with teprotumumab, an insulin-like growth factor I receptor inhibitor (10 mg/kg for the first infusion then 20 mg/kg for subsequent infusions, every three weeks for a total 8 infusions). This study included patients with acute and chronic thyroid eye disease (TED) with DON who had failed conventional therapies and were not candidates for surgical decompression. Data collected included best corrected visual acuity (BCVA), color vision, RAPD when present, and orbital CT or MRI. Proptosis, clinical activity score (CAS), Gorman diplopia score (GDS), and Humphrey visual fields (HVF) were also evaluated.Ten patients (6 women, 4 men) with an average age 64 years old were included in this study. Mean follow up after completion of infusions was 15 weeks. Baseline visual acuity (VA) impairment ranged from hand motion (HM) to 20/25 in affected eyes. All patients had pre-treatment orbital CT or MRI that confirmed orbital apex compression. Seventy percent of patients had objective improvement in DON after 2 infusions of teprotumumab measured as significant improvement in visual acuity, resolution of RAPD, or both. After completion of treatment, affected eyes had a mean BCVA improvement of 0.87 logMAR (p=0.0207), proptosis reduction of 4.7 mm (p<0.00001), CAS improvement of 5.25 points (p<0.00001), and GDS improvement of 0.75 points (p=0.160). All 6 patients who presented with an RAPD had resolution or improvement of RAPD. All 7 patients who presented with color vision deficits had normalization or improvement of color vision.Conclusions and Importance: Teprotumumab infusions resulted in medical decompression and objective resolution or improvement of dysthyroid optic neuropathy. Most patients had rapid improvement of visual acuity and reversal of RAPD. Post-infusion imaging demonstrated reduction in extraocular muscle size that correlated with improvement in visual dysfunction. However, patients who presented with longstanding severe visual loss had limited improvement. There was no recurrence of DON after completion of teprotumumab in our cohort.

    View details for DOI 10.1016/j.ajoc.2021.101111

    View details for PubMedID 34113737

  • Ophthalmic artery occlusion following n-butyl cyanoacrylate embolization of an orbital arteriovenous malformation. Orbit (Amsterdam, Netherlands) Shoji, M. K., Tran, A. Q., Lee, W. W., Dubovy, S. R., Kossler, A. L. 2021: 1-7


    A 33-year-old pregnant woman presented with six months of right-sided proptosis. Neuroimaging revealed a right orbital arteriovenous malformation arising from the second segment of the ophthalmic artery. As she was 9weeks pregnant, the decision was made to monitor her closely. Over the following six months, her proptosis progressed, accompanied by decreased visual acuity, afferent pupillary defect, and red desaturation concerning for compressive optic neuropathy. After planned c-section, she underwent embolization with n-butyl cyanoacrylate. Upon awakening after embolization, she had no light perception vision from her right eye and was found to have ophthalmic artery obstruction. She ultimately developed a blind painful right eye and underwent enucleation with histopathology demonstrating glue in the central retinal artery, posterior ciliary arteries, and choroid. This case highlights ophthalmic artery occlusion as a rare complication of orbital arteriovenous malformation embolization and demonstrates correlating histopathological findings, which have not previously been reported.

    View details for DOI 10.1080/01676830.2021.1955937

    View details for PubMedID 34365893

  • Teprotumumab for the treatment of chronic thyroid eye disease. Eye (London, England) Ugradar, S., Kang, J., Kossler, A. L., Zimmerman, E., Braun, J., Harrison, A. R., Bose, S., Cockerham, K., Douglas, R. S. 2021


    BACKGROUND: Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of active Thyroid eye disease (TED). The current study reviews its efficacy in chronic TED.METHODS: In this retrospective review, consecutive patients with chronic stable TED (>2 years), who had received ≥3 infusions of teprotumumab were included. All patients had measurements of proptosis, and calculation of the CAS and diplopia scores before and after therapy. Five-point strabismus scores were also calculated. Patients who had imaging within 4 months prior to therapy and 6 weeks post therapy underwent orbital 3D volumetric analysis.RESULTS: Thirty-one patients met the inclusion criteria. The mean (SD) duration of TED was 81 months (56) and the mean (SD) number of infusions received by each patient was 7 (2). Mean (SD) reduction in proptosis for each study orbit was 3.5mm (0.4) and 3mm (0.3) for the fellow orbit. The CAS response was 90% for the study orbit and 87% for the fellow orbit. Of the 15 patients who had diplopia at baseline, 67% had a clinically significant response, while 47% had complete resolution following treatment. Following teprotumumab, mean (SD) reduction of muscle tissue was 2011mm3 (1847) in the study orbit and 1620mm3 (1759) in the fellow orbit. The mean (SD) reduction of fat volume was 2101 mm3 (1681) in the study orbit and 1370mm3 (1181) in the fellow orbit.CONCLUSION: Teprotumumab significantly reduces proptosis, inflammation, diplopia, strabismus and orbital soft tissue volume in patients with chronic TED.

    View details for DOI 10.1038/s41433-021-01593-z

    View details for PubMedID 34244669

  • Thyroid Eye Disease: Navigating the New Treatment Landscape. Journal of the Endocrine Society Dosiou, C., Kossler, A. L. 2021; 5 (5): bvab034


    Thyroid eye disease (TED) is a complex inflammatory disease that can have a long clinical course with sight-threatening and debilitating ocular sequelae. Until recently, there were limited therapeutic options available. In the last decade we have gained a deeper understanding of the underlying pathophysiology, which has led to the development of novel effective targeted therapies. This article discusses the challenges encountered in the clinical evaluation and treatment of TED patients, with the goal to empower endocrinologists and ophthalmologists to work together to provide effective multidisciplinary care. We will review recommendations of past clinical guidelines around evaluation and management of TED patients, discuss the randomized controlled trials of new biologic therapies, and explore how to navigate the emerging therapeutic landscape.

    View details for DOI 10.1210/jendso/bvab034

    View details for PubMedID 33948524

  • New Indicator of Children's Excessive Electronic Screen Use and Factors in Meibomian Gland Atrophy. American journal of ophthalmology Cremers, S. L., Khan, A. R., Ahn, J., Cremers, L., Weber, J., Kossler, A. L., Pigotti, C., Martinez, A. 2021


    PURPOSE: To evaluate the association of children's daily-electronic-screen-use with severe meibomian-gland-atrophy (MGA).DESIGN: Retrospective cross-sectional study METHODS: Children (6-17years) presenting at clinical practice December 2016-2017 were evaluated for ≥grade 2 MGA versus age-matched-controls with insignificant atrophy (

    View details for DOI 10.1016/j.ajo.2021.03.035

    View details for PubMedID 33857506

  • Multi-compartment skull base orbital cavernous venous malformation: A rare presentation of a common orbital mass. American journal of ophthalmology case reports Azad, A. D., Sears, C. M., Hwang, P. H., Mohyeldin, A., Fernandez-Miranda, J., Kossler, A. L. 2021; 21: 101020


    Purpose: We present a unique case of an orbital intraconal cavernous venous malformation that extended along the trigeminal nerve to the pterygopalatine and middle cranial fossa. Our aim is to describe an atypical presentation of this common orbital vascular mass.Observations: A 57-year-old female presented with right eye proptosis. Orbital magnetic resonance imaging demonstrated a lobulated contrast-enhancing mass involving the right intraconal orbital space, pterygopalatine fossa, and right middle cranial fossa, radiographically presumed to be a schwannoma. Intraoperative and histopathologic evaluation confirmed a cavernous venous malformation that extended along the trigeminal nerve. The mass, including its attachments to the cranial nerves and dura, was successfully removed via a combined transorbital and endoscopic endonasal approach. The patient recovered well with 20/20 vision, full extraocular movements, and resolution of proptosis.Conclusions: This a rare presentation of an orbital cavernous venous malformation not previously described. Cavernous venous malformations typically present as ovoid well-circumscribed lesions; however, they can also extend outside the orbit along the path of cranial nerves, as was observed in this case. These types of lesions should be included in the differential diagnosis of masses arising from or extending along cranial nerves, even when involving the orbit.

    View details for DOI 10.1016/j.ajoc.2021.101020

    View details for PubMedID 33598587

  • Genome Sequencing and Apoptotic Markers to Assess Treatment Response of Lacrimal Gland Adenoid Cystic Carcinoma to Intra-Arterial Cytoreductive Chemotherapy. Ophthalmic plastic and reconstructive surgery Yu, M. D., Men, C. J., Do, H., Colevas, A. D., Lin, J. H., Egbert, P. R., Tse, D. T., Kossler, A. L. 2021


    Adenoid cystic carcinoma of the lacrimal gland is an aggressive, malignant epithelial neoplasm. We report the case of a 30-year-old male with lacrimal gland adenoid cystic carcinoma treated with neoadjuvant intra-arterial chemotherapy through the internal carotid artery, followed by orbital exenteration and chemoradiation. Treatment response was evaluated using a novel combination of pre- and posttreatment genome sequencing coupled with immunohistochemical evaluation, which showed diffuse tumor apoptosis. A posttreatment decrease in variant allele frequency of the NOTCH1 mutation, and robust tumor cytoreduction on imaging, supports exploration of NOTCH1 analysis as a potential marker of cisplatin sensitivity. The use of genome sequencing and immunohistochemical evaluation could provide a more targeted therapeutic assessment of neoadjuvant intra-arterial chemotherapy in the management of lacrimal gland adenoid cystic carcinoma.

    View details for DOI 10.1097/IOP.0000000000002079

    View details for PubMedID 34798653

  • Ocular, Orbital, and Adnexal Toxicity With High-dose Volumetric Modulated Arc Radiation Therapy For Orbital Malignancies. Ophthalmic plastic and reconstructive surgery Garcia, G. A., Charlson, E. S., Kolseth, C., Kim, N., Kossler, A. L. 2021


    Conventional modalities of external-beam radiation therapy (EBRT) are associated with high incidences of severe vision-threatening ocular and orbital toxicities when used to treat orbital malignancies. We investigate toxicities associated with high-dose volumetric modulated arc therapy (VMAT), a commonly used contemporary treatment modality for these tumors.Retrospective analysis of malignant orbital tumors managed with adjuvant high-dose VMAT preceded by globe-salvaging surgical therapy (GST) or exenteration. Dosimetric quantitation of target volumes and critical structures was performed. Incidence and severity of ocular, orbital, and adnexal toxicities were evaluated and assessed with regard to conventional EBRT toxicities for orbital malignancies described in the literature.Eighty-four subjects (mean age = 65.9 ± 9.7 years) were included (N = 48 and N = 36 in GST and exenteration subgroups, respectively). Mean dose was 64.8 ± 2.1 Gy to the planning target volume. Dosing to critical structures typically did not surpass known tissue tolerance limits. Median follow up was 18.3 months. Visual acuity in the GST subgroup was not significantly different after VMAT (0.25 ± 0.06) compared with baseline (0.23 ± 0.02; P = 0.302). Whereas severe toxicities reported by major systematic analyses in the literature with older EBRT modalities were relatively common-for example, retinopathy (16-40%), optic neuropathy (16%), and corneal perforation (13%)-toxicities with VMAT were typically mild and less common. The most common toxicities with VMAT were mild dry eye (81.3%; 39/48), cataract (21.1%; 8/38 phakic eyes), and periocular dermatitis (15.5%; 13/84). Vision-threatening toxicities, including severe corneal pathologies, retinopathy, or optic neuropathy, were rare. There were no contralateral ocular or adnexal toxicities.High-dose VMAT for orbital malignancies demonstrated low incidence and severity of eye-related toxicity, in contradistinction to adverse events reported from conventional forms of radiotherapy.

    View details for DOI 10.1097/IOP.0000000000002001

    View details for PubMedID 34284423

  • Stimulating Tear Production: Spotlight on Neurostimulation. Clinical ophthalmology (Auckland, N.Z.) Yu, M. D., Park, J. K., Kossler, A. L. 2021; 15: 4219-4226


    Dry eye disease (DED) affects up to one-third of the global population. Traditional therapies, including topical lubricants, have been employed with variable success in the treatment of DED. Recently, neurostimulation of the lacrimal functional unit (LFU) has emerged as a promising alternative therapy for DED. In this review, we describe the neuroanatomical and pathophysiological considerations of DED and the LFU that make neurostimulation a viable therapeutic alternative. We further detail the various neurostimulatory approaches taken thus far-from implanted stimulators to external devices to chemical neurostimulation. Existing studies reveal the strengths of the neurostimulatory approach in increasing tear volume and improving dry eye symptoms, but further studies are needed to elucidate its true potential in treatment of DED.

    View details for DOI 10.2147/OPTH.S284622

    View details for PubMedID 34707341

  • Perioperative management of antithrombotic medications: An investigation into current U. S. ophthalmologic recommendations Journal of Current Ophthalmology Garcia, G. A., Bair, H., Kossler, A. L. 2021; 33 (2): 182-188

    View details for DOI 10.4103/2452-2325.303201

  • Updates on the understanding and management of thyroid eye disease. Therapeutic advances in ophthalmology Men, C. J., Kossler, A. L., Wester, S. T. 2021; 13: 25158414211027760


    Thyroid eye disease (TED) is a complex disease associated with myriad clinical presentations, including facial disfigurement, vision loss, and decreased quality of life. Traditionally, steroid therapy and/or radiation therapy were commonly used in the treatment of active TED. While these therapies can help reduce inflammation, they often do not have a sustainable, significant long-term effect on disease outcomes, including proptosis and diplopia. Recent advances in our understanding of the pathophysiology of TED have shifted the focus of treatment toward targeted biologic therapies. Biologics have the advantage of precise immune modulation, which can have better safety profiles and greater efficacy compared to traditional approaches. For instance, the insulin-like growth factor-1 receptor (IGF-1R) has been found to be upregulated in TED patients and to colocalize with the thyroid-stimulating hormone receptor (TSHR), forming a signaling complex. Teprotumumab is an antibody targeted against IGF-1R. By inhibiting the IGF-1R/TSHR signaling pathway, teprotumumab may reduce the production of proinflammatory cytokines, hyaluronan secretion, and orbital fibroblast activation in patients with TED. Due to promising phase II and III clinical trial results, teprotumumab has become the first biologic US Food and Drug Administration (FDA)-approved for the treatment of TED. In addition, there are currently ongoing studies looking at the use of antibodies targeting the neonatal Fc receptor (FcRn) in various autoimmune diseases, including TED. FcRn functions to transport immunoglobulin G (IgG) and prevent their lysosomal degradation. By blocking the recycling of IgG, this approach may dampen the body's immune response, in particular the pathogenic IgG implicated in some autoimmune diseases. Advances in our understanding of the pathophysiology of TED, therefore, are leading to more targeted therapeutic options, and we are entering an exciting new phase in the management of TED. This review will cover recent insights into the understanding of TED pathophysiology and novel treatment options as well as ongoing studies of new potential treatment options for TED.

    View details for DOI 10.1177/25158414211027760

    View details for PubMedID 34263138

  • Microphthalmia and orbital cysts in DiGeorge syndrome. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus Chandramohan, A., Sears, C. M., Huang, L. C., Beres, S., Fredrick, D., Kossler, A. L. 2021

    View details for DOI 10.1016/j.jaapos.2021.06.001

    View details for PubMedID 34597781

  • A deep learning approach to identify blepharoptosis by convolutional neural networks. International journal of medical informatics Hung, J. Y., Perera, C. n., Chen, K. W., Myung, D. n., Chiu, H. K., Fuh, C. S., Hsu, C. R., Liao, S. L., Kossler, A. L. 2021; 148: 104402


    Blepharoptosis is a known cause of reversible vision loss. Accurate assessment can be difficult, especially amongst non-specialists. Existing automated techniques disrupt clinical workflow by requiring user input, or placement of reference markers. Neural networks are known to be effective in image classification tasks. We aim to develop an algorithm that can accurately identify blepharoptosis from a clinical photo.A total of 500 clinical photographs from patients with and without blepharoptosis were sourced from a tertiary ophthalmic center in Taiwan. Images were labeled by two oculoplastic surgeons, with an independent third oculoplastic surgeon to adjudicate disagreements. These images were used to train a series of convolutional neural networks (CNNs) to ascertain the best CNN architecture for this particular task.Of the models that trained on the dataset, most were able to identify ptosis images with reasonable accuracy. We found the best performing model to use the DenseNet121 architecture without pre-training which achieved a sensitivity of 90.1 % with a specificity of 82.4 %, compared to the worst performing model which was used a Resnet34 architecture with pre-training, achieving a sensitivity of 74.1 %, and specificity of 63.6 %. Models with and without pre-training performed similarly (mean accuracy 82.6 % vs. 85.8 % respectively, p = 0.06), though models with pre-training took less time to train (1-minute vs. 16 min, p < 0.01).We report the use of AI to accurately diagnose blepharoptosis from a clinical photograph with no external reference markers or user input requirement. Most current-generation CNN architectures performed reasonably on this task, with the DenseNet121, and Resnet18 architectures without pre-training performing best in our dataset.

    View details for DOI 10.1016/j.ijmedinf.2021.104402

    View details for PubMedID 33609928

  • Cannibalistic bilateral orbital trauma. American journal of ophthalmology case reports Rosenblatt, T. R., Garcia, G. A., Johnson, T. E., Kossler, A. L. 2020; 20: 100983


    Purpose: To describe the details of a unique case of cannibalistic orbital trauma and the oculoplastic reconstruction approach.Observations: A 65-year-old homeless man survived a disfiguring cannibalistic facial and bilateral orbital injury that included bilateral loss of all adnexal structures, partial exenteration of the left orbit, and severe damage to the right globe and anterior orbital structures. The patient's extensive facial and orbital tissue damage required emergent surgery, which included left exenteration and right eyelid reconstruction.Conclusions: This is the first report of cannibalistic evisceration in a live victim who survived the attack, posing a unique reconstructive challenge. Bilateral globe removal was avoided to provide time for the patient's emotional recovery. Although this was an exceptional surgical scenario, traditional oculoplastic principles remained crucial to achieving a successful outcome. The patient survived and was pleased with his surgical outcome, refusing further reconstruction or prosthesis fitting.

    View details for DOI 10.1016/j.ajoc.2020.100983

    View details for PubMedID 33163692

  • Corneal Neurotization and Novel Medical Therapies for Neurotrophic Keratopathy CURRENT OPHTHALMOLOGY REPORTS Rosenblatt, T. R., Sears, C. M., Park, J., Kossler, A. 2020; 8 (4): 252-266
  • Outcomes of corneal neurotisation using processed nerve allografts: a multicentre case series. The British journal of ophthalmology Sweeney, A. R., Wang, M., Weller, C. L., Burkat, C., Kossler, A. L., Lee, B. W., Yen, M. T. 2020


    BACKGROUND: Corneal neurotisation is a rapidly evolving procedure treating neurotrophic keratopathy. The variety of surgical techniques used and corresponding outcomes after corneal neurotisation are not well understood. This study describes the techniques and outcomes in the largest case series of corneal neurotisation using processed nerve allografts to date.METHODS: This is a retrospective case series of patients who underwent corneal neurotisation with human cadaveric processed nerve allografts. All patients had preoperative and postoperative description of best corrected visual acuity and measurement of corneal sensation. Comparative studies after stratification of techniques were performed.RESULTS: A total of 17 patients were identified. The cause of corneal anaesthesia was prior infection in eight cases, trigeminal nerve palsy in eight cases and ocular trauma in one case. There were no intraoperative or postoperative complications. Following neurotisation surgery, the time to first gain of corneal sensation and maximal gain of sensation occurred at a mean of 3.7 months (range 1-8 months) and 6.6 months (range 3-15 months), respectively. The mean preoperative and postoperative corneal sensation as measured by Cochet-Bonnet aesthesiometry was 0.36cm (range 0-3.2cm) and 4.42cm (range 0-6cm), respectively (p<0.01). Visual acuity was unchanged after neurotisation. There were no statistical differences in outcomes based on end-to-end versus end-to-side coaptations, donor nerve selection or laterality of donor nerve.CONCLUSION: Corneal neurotisation with processed nerve allografts is a safe and effective procedure. This study provides further evidence for the use of processed nerve allografts for corneal neurotisation.

    View details for DOI 10.1136/bjophthalmol-2020-317361

    View details for PubMedID 33199302

  • Bilateral Atypical Eyelid Lesions in a 50-Year-Old Woman. JAMA ophthalmology Azad, A. D., Charlson, E. S., Kossler, A. L. 2020

    View details for DOI 10.1001/jamaophthalmol.2020.2090

    View details for PubMedID 33057579

  • Progress Towards Parity: Female Representation in the American Society of Ophthalmic Plastic and Reconstructive Surgery. Ophthalmic plastic and reconstructive surgery Azad, A. D., Rosenblatt, T. R., Chandramohan, A., Fountain, T. R., Kossler, A. L. 2020


    PURPOSE: To report female representation within the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) at all levels of career achievement over 50 years.METHODS: Data were extrapolated from published ASOPRS directories and the 50th anniversary booklet. Fellowship, membership, leadership, and awards data were evaluated over 5 decades. Comparisons were made between the first and second 25 years, proportions of early and late career achievements, and time to career progression between males and females.RESULTS: During the first decade, 5.6% of ASOPRS fellows were female (n = 2), which rose to 6.6% (n = 8), 17.6% (n = 32), 22.4% (n = 35), and 39.4% (n = 97) in the second, third, fourth, and fifth decades, respectively. These patterns were echoed in ASOPRS membership. When comparing the first half (1969-1994) to the second half (1995-2018), fellowship (10.5% vs. 30.0%, p < 0.001), membership (8.0% vs. 30.3%, p < 0.001), early career awards (5.6% vs. 28.9%, p = 0.047), program directorship (0.0% vs. 15.7%, p = 0.017), and executive committee female representation (4.5% vs. 16.8%, p < 0.001) increased significantly. However, females were proportionally underrepresented as program directors (p = 0.003), late career award winners (p = 0.001), executive committee members (p < 0.001), and presidents (p = 0.020). Among those reaching leadership positions, females took longer than males to become program directors by a median of 4 years (p = 0.025).CONCLUSIONS: There has been a steady increase in female representation in ASOPRS fellowship training and membership. While significant progress has been made, growth in female leadership and award recognition is still needed.

    View details for DOI 10.1097/IOP.0000000000001764

    View details for PubMedID 32675720

  • Retrospective Analysis of Incidence Rates of Benign and Malignant Eyelid Lesions at a San Francisco Bay Area Tertiary Hospital Gali, H. E., Kim, Y., Lian, R., Chea, L., Ahmadian, S., Kossler, A., Erickson, B., Born, D., Basham, R., Egbert, P., Lin, J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • Treatment Pathways and Geographic Variation in Thyroid Eye Disease Patient Care: Analysis of Commercially-Insured Patients, 2008-2016 Azad, A., Kossler, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • Teprotumumab for Dysthyroid Optic Neuropathy: Early Response to Therapy. Ophthalmic plastic and reconstructive surgery Sears, C. M., Azad, A. D., Dosiou, C. n., Kossler, A. L. 2020


    A 45-year-old male presented with active progressive thyroid eye disease refractory to intravenous steroids and right orbital radiation. Visual acuity, left relative afferent pupillary defect, and Humphrey visual field defects were consistent with worsening left dysthyroid optic neuropathy. Orbital MRI demonstrated extraocular muscle enlargement and effacement of the left optic nerve sheath. After 2 infusions of teprotumumab, the patient's visual acuity, relative afferent pupillary defect, Humphrey visual fields, proptosis, and extraocular muscle size improved. This is the first report of dysthyroid optic neuropathy responsive to teprotumumab, and it supports the need for further studies to better understand the role of teprotumumab in treating sight-threatening thyroid eye disease.

    View details for DOI 10.1097/IOP.0000000000001831

    View details for PubMedID 32976335

  • Corneal Neurotization: A Surgical Treatment for Neurotrophic Keratopathy. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Kolseth, C. M., Charlson, E. S., Kossler, A. L. 2020

    View details for DOI 10.1097/WNO.0000000000000879

    View details for PubMedID 32349065

  • Corneal Neurotization: A Review of Pathophysiology and Outcomes. Ophthalmic plastic and reconstructive surgery Park, J. K., Charlson, E. S., Leyngold, I. n., Kossler, A. L. 2020


    The objective of this study is to provide a systematic review of the clinical outcomes of corneal neurotization and present the pathophysiology of corneal wound healing, neurotrophic keratopathy, and corneal neurotization.A literature review of published articles and meeting abstracts between December 2008 and February 2019 in the English language with the terms "corneal neurotization," "corneal neurotisation," "corneal reinnervation," and "neurotrophic keratopathy" was performed. Reported clinical data before and after corneal neurotization, and surgical techniques, were collected and analyzed.A total of 54 eyes that underwent corneal neurotization were identified. Final Logarithm of the Minimum Angle of Resolution (logMAR) best-corrected visual acuity improved to 0.85 (standard deviation [SD] = 0.65) from 1.25 (SD = 0.71) with a mean improvement of 0.41 (SD = 0.55; p < 0.0001). Central corneal sensation measured using Cochet-Bonnet esthesiometer improved from 2.18 mm (SD = 0.4) to 40.10 mm (SD = 18.66) with a mean filament length change of 38.00 mm (SD = 18.95; p < 0.0001). The median time to the reported maximal sensation return was 8 months (interquartile range 6-10). The most common reported limitation to visual recovery was corneal scarring (31.5%). Children (ages 0-17 years) as compared with adults (ages 18-82 years) had significantly greater final central corneal sensation esthesiometry readings, central corneal sensation return, and improvement in the logMAR best-corrected visual acuity (p < 0.011).Neurotrophic keratopathy disturbs the homeostatic balance of trophic factors and trigeminal nerve reflexes needed to support ocular surface health and corneal healing. Corneal neurotization can significantly improve corneal sensation and visual acuity and should be considered for the treatment of refractory neurotrophic keratopathy, especially in pediatric populations.

    View details for DOI 10.1097/IOP.0000000000001583

    View details for PubMedID 31923091

  • Radiation-Induced Hyalinizing Clear Cell Carcinoma of the Orbit. Ophthalmic plastic and reconstructive surgery Topping, K. L., Ortiz, A. n., Lin, J. H., Kossler, A. L. 2020


    Radiation-induced malignancy is rare, occurring in approximately 0.4%-1.0% of patients receiving external beam radiation therapy. Sarcomas and squamous cell carcinomas are among the most common types of cancers to occur. A 74-year-old woman presented with redness and swelling in the right periorbital region. She had history of multiple recurrent ameloblastoma of the right maxilla, invading the right orbital floor status post 4 surgical resections and 66 Gray external beam radiotherapy 5 years prior. MRI showed a poorly circumscribed mass involving the inferior and lateral orbit. Orbital biopsy revealed clear cell carcinoma with hyalinizing sclerosis and Ewing sarcoma breakpoint region 1 gene arrangement. Due to the extent of orbital disease and presence of perineural invasion, she underwent orbital exenteration. Hyalinizing clear cell carcinoma, a rare cancer, has not been reported to occur in the orbit following radiation. This case highlights the importance of lifetime monitoring in patients who have undergone radiation therapy.

    View details for DOI 10.1097/IOP.0000000000001708

    View details for PubMedID 32427738

  • Microsurgical Resection of an Orbital Arteriovenous Malformation With Intraoperative Digital Subtraction Angiography. Ophthalmic plastic and reconstructive surgery Rosenblatt, T. R., Myung, D. n., Fischbein, N. J., Steinberg, G. K., Kossler, A. L. 2020

    View details for DOI 10.1097/IOP.0000000000001815

    View details for PubMedID 32976328

  • Chronic Electrical Stimulation for Tear Secretion: Lacrimal vs. anterior ethmoid nerve. The ocular surface Kossler, A. L., Brinton, M., Patel, Z. M., Dalal, R., Ta, C. N., Palanker, D. 2019


    PURPOSE: To evaluate and compare the effect of lacrimal nerve stimulation (LNS) and anterior ethmoid nerve stimulation (AENS) on aqueous tear secretion, and tissue condition following chronic implantation.METHODS: A neurostimulator was implanted in rabbits adjacent to the (1) lacrimal nerve, and (2) anterior ethmoid nerve. Tear volume was measured with Schirmer test strips after stimulation (2.3-2.8 mA pulses at 30 Hz for 3-5 min), and scores were compared to sham stimulation. Lacrimal gland and nasal septal tissue were evaluated histologically after chronic stimulation (2 weeks-7 months).RESULTS: LNS increases tear volume by 32% above sham (p < 0.05, n = 5), compared with 133% for AENS (p ≤ 0.01, n = 6). AENS also significantly increases tear secretion in the fellow, non-stimulated eye (p ≤ 0.01, n = 6), as expected from the tearing reflex pathway. Histologically, chronic LNS is well tolerated by surrounding tissues while chronic AENS results in nasal mucosal fibrosis and implant extrusion within 3 weeks.CONCLUSIONS: AENS is significantly more effective than LNS at enhancing aqueous tear secretion, including the fellow eye. The lacrimal implant is well tolerated, while the nasal implant requires further design optimization to improve tolerability.

    View details for DOI 10.1016/j.jtos.2019.08.012

    View details for PubMedID 31476515

  • Incidence of Perineural Invasion with Hedgehog Pathway Inhibitors in Orbital and Periorbital Basal Cell Carcinoma Chandramohan, A., Nair, A., Chang, A., Kossler, A. L. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Neurostimulation for tear production. Current opinion in ophthalmology Park, J. K., Cremers, S. n., Kossler, A. L. 2019; 30 (5): 386–94


    Dry eye disease (DED) is a chronic multifactorial disease that affects millions of people worldwide. Despite ongoing research, treatment for DED remains a challenge. Neurostimulation for tear production is a rapidly evolving field that culminated in the development of the intranasal tear neurostimulator (ITN). In this article, we review the neuroanatomy and pathophysiology of tear production and the evolution of neurostimulation for the treatment of DED.The ITN was approved for commercial use in April 2017. This innovation stemmed from the success of lacrimal nerve and anterior ethmoid nerve stimulation animal studies. Since then, numerous pilot studies and multicenter randomized controlled trials demonstrate increased aqueous tear production, improved DED-related symptoms, and device safety. Recent studies also report the positive effects of intranasal stimulation on mucin and lipid secretion.Neurostimulation for enhanced tear production is a promising new treatment option for DED. Stimulation of the lacrimal nerve and anterior ethmoid nerve both effectively increase tear volume. The ITN is a noninvasive device that effectively increases aqueous tear volume and may improve tear composition, including mucin and lipid concentrations. Further studies are needed to determine proper patient selection and the long-term efficacy of neurostimulation for DED.

    View details for DOI 10.1097/ICU.0000000000000590

    View details for PubMedID 31393326

  • Orbital, eyelid, and nasopharyngeal silicone oil granuloma presenting as ptosis & pseudo-xanthelasma. American journal of ophthalmology case reports Powers, M. A., Wood, E. H., Erickson, B. P., Singh, K., Sanislo, S. R., Kossler, A. L. 2018; 11: 45–48


    Purpose: To highlight the presentation and management of a patient with eyelid, orbital and nasopharyngeal silicone oil migration through a glaucoma drainage implant presenting as pseudo-xanthelasma and ptosis.Observations: A 68-year male presented with unilateral ptosis and presumed xanthelasma. He had a history of glaucoma drainage implant surgery, pseudophakia, and multiple retinal detachment repairs with silicone oil. During ptosis repair it was discovered that his presumed xanthelasma was in fact an eyelid silicone granuloma. Additional work up revealed silicone infiltration of the eyelids, orbits, and nasopharynx, resulting from emulsified silicone oil leakage through his glaucoma valve implant.Conclusions and Importance: Silicone oil may emulsify with time, with potential egress via a glaucoma filtration device. Clinicians should be alert for eyelid, orbital and sinonasal findings that may indicate occult migration.

    View details for PubMedID 29978139

  • Orbital and chorioretinal manifestations of Erdheim-Chester disease treated with vemurafenib. American journal of ophthalmology case reports Huang, L. C., Topping, K. L., Gratzinger, D., Brown, R. A., Martin, B. A., Silva, R. A., Kossler, A. L. 2018; 11: 158–63


    Purpose: We report a patient with severe multi-organ dysfunction of unknown origin who presented with bilateral orbital and chorioretinal manifestations that led to the diagnosis of Erdheim-Chester Disease (ECD).Observations: ECD is a rare, histiocytic, proliferative disorder characterized by multi-systemic organ involvement that has historically lacked effective therapy. Our patient underwent genetic testing that was positive for the BRAF V600E mutation; therefore, the patient was treated with vemurafenib.Conclusions and importance: This case demonstrates the rare orbital and intraocular manifestations of ECD and the unfortunate impact of a delayed diagnosis, the importance of early gene therapy testing for management decisions, and the utilization of targeted directed therapy to improve visual outcomes and quality of life.

    View details for PubMedID 30094395

  • Hedgehog Pathway Inhibitors as Neoadjuvant Therapy for Orbital/Periorbital Basal Cell Carcinoma Chandramohan, A., Nair, A., Chang, A. L., Kossler, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Fundus Flavoprotein Autofluorescence in Compressive Optic Neuropathy Topping, K., Cockerham, K., Kossler, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Disseminated silicone granulomatosis in the face and orbit. American journal of ophthalmology case reports Chen, T. A., Mercado, C. L., Topping, K. L., Erickson, B. P., Cockerham, K. P., Kossler, A. L. 2018; 10: 32–34


    Purpose: To report a case of disseminated silicone granulomatosis presenting with ptosis, proptosis and vision loss.Observations: A 56-year-old female presented with ptosis, proptosis, and vision loss and was noted to have palpable, erythematous masses involving the orbit, face, trunk, and body. She had a history of bilateral silicone breast implants and cosmetic facial filler injections. Orbital biopsy demonstrated non-caseating granulomas with foreign-body giant cells and vacuoles containing material consistent with silicone. Removal of the patient's breast implants and systemic immunosuppression led to dramatic granuloma regression.Conclusions: Silicone can induce a severe, systemic inflammatory response and should be considered in the differential for facial and periorbital granulomas in patients with a history of silicone breast implants. Management of disseminated silicone granulomatosis is challenging and requires multimodal treatment with silicone removal and systemic immunomodulation.

    View details for PubMedID 29780909

  • Enhanced natural tearing by electrical stimulation of the anterior ethmoid nerve Brinton, M., Kossler, A., Patel, Z., Loudin, J., Franke, M., Ta, C., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2017
  • Enhanced Tearing by Electrical Stimulation of the Anterior Ethmoid Nerve INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Brinton, M., Kossler, A. L., Patel, Z. M., Loudin, J., Franke, M., Ta, C. N., Palanker, D. 2017; 58 (4): 2341-2348


    Electrical neurostimulation enhances tear secretion, and can be applied to treatment of dry eye disease. Using a chronic implant, we evaluate the effects of stimulating the anterior ethmoid nerve on the aqueous, lipid, and protein content of secreted tears.Neurostimulators were implanted beneath the nasal mucosa in 13 New Zealand white rabbits. Stimulations (2.3-2.8 mA pulses of 75-875 μs in duration repeated at 30-100 Hz for 3 minutes) were performed daily, for 3 weeks to measure changes in tear volume (Schirmer test), osmolarity (TearLab osmometer), lipid (Oil-Red-O staining), and protein (BCA assay, mass spectrometry).Stimulation of the anterior ethmoid nerve in the frequency range of 30 to 90 Hz increased tear volume by 92% to 133% (P ≤ 0.01). Modulating the treatment with 50% duty cycle (3 seconds of stimulation repeated every 6 seconds) increased tear secretion an additional 23% above continuous stimulation (P ≤ 0.01). Tear secretion returned to baseline levels within 7 minutes after stimulation ended. Tear film osmolarity decreased by 7 mOsmol/L, tear lipid increased by 24% to 36% and protein concentration increased by 48% (P ≤ 0.05). Relative abundance of the lacrimal gland proteins remained the same, while several serum and corneal proteins decreased with stimulation (P ≤ 0.05).Electrical stimulation of the anterior ethmoid nerve increased aqueous tear volume, reduced tear osmolarity, added lipid, and increased the concentration of normal tear proteins. Human studies with an intranasal stimulator should verify these effects in patients with aqueous- and lipid-deficient forms of dry eye disease.

    View details for DOI 10.1167/iovs.16-21362

    View details for PubMedID 28431436

  • Current Trends in Upper and Lower Eyelid Blepharoplasty Among American Society of Ophthalmic Plastic and Reconstructive Surgery Members. Ophthalmic plastic and reconstructive surgery Kossler, A. L., Peng, G. L., Yoo, D. B., Azizzadeh, B., Massry, G. G. 2017


    To assess current practice patterns for management of upper and lower eyelid blepharoplasty by active American Society of Ophthalmic Plastic and Reconstructive Surgery members.An invitation to participate in a web-based anonymous survey was sent to the active American Society of Ophthalmic Plastic and Reconstructive Surgery membership via email. The survey consists of 34 questions, both multiple choice and free response, regarding upper and lower eyelid blepharoplasty surgery. Practice patterns for both aesthetic and functional blepharoplasty are assessed.Thirty-four percent (161/472) of American Society of Ophthalmic Plastic and Reconstructive Surgery members polled responded to the survey. Members perform an average of 196 upper eyelid, 46 lower eyelid, and 53 four-eyelid blepharoplasty procedures per year, with 70% of cases being functional and 30% purely aesthetic. Most members prefer monitored care (71%) to local (21%) or general (8%) anesthesia. Eighty-nine percent of surgeons use topical antibiotics after surgery, erythromycin being the most common (51%). Fourteen percent of members use postoperative oral antibiotics, with cephalexin (81%) being most common. In upper eyelid blepharoplasty, orbicularis muscle is excised by 86% of respondents. Orbital fat is excised, when deemed appropriate, in 97% of cases, with nasal fat excised most commonly (88%). Less commonly, fat repositioning (36%) and adjunctive fat grafting (33%) are performed. In lower eyelid blepharoplasty, surgeons report using one or more of the following approaches: transconjunctival (96%), transcutaneous (82%), and both transconjunctival and transcutaneous (51%). Common adjunctive procedures include orbital fat excision (99%), fat repositioning (80%), and lateral canthal suspension (96%). Less common adjunctive procedures include laser skin resurfacing (36%) and chemical peels (29%).This report outlines contemporary practice patterns among active American Society of Ophthalmic Plastic and Reconstructive Surgery members in the management of upper and lower eyelid blepharoplasty. It is important to quantify such data periodically to update the membership as to how this common surgical procedure is approached. This also allows eyelid surgeons to compare their practice patterns with a national group specializing in such surgery.

    View details for DOI 10.1097/IOP.0000000000000849

    View details for PubMedID 28151825

  • Silicone Oil-Induced Nasal Polyposis: A Case Report. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Patel, V. S., Hwang, P. H., Kossler, A. L., Choby, G. n. 2017: 194599817728896

    View details for PubMedID 28871877

  • Exaggerated Oculocardiac Reflex Elicited by Local Anesthetic Injection of an Empty Orbit: A Case Report. A & A case reports Nicholson, D. n., Kossler, A. n., Topping, K. n., Stary, C. M. 2017


    We report the first description of oculocardiac reflex elicited with injection of local anesthetic in an empty orbit, and highlight clinical indicators for patients that may be at risk for an exaggerated oculocardiac reflex. We describe a patient with prior head and eye trauma treated for anophthalmic socket reconstruction at an outpatient eye surgery center. Injection of local anesthetic into the empty orbit induced an extended sinus arrest. This exaggerated response was avoided in a subsequent surgery by pretreatment with high-dose anticholinergics.

    View details for DOI 10.1213/XAA.0000000000000609

    View details for PubMedID 28767475

  • Lateral Canthal Tendon Disinsertion: Clinical Characteristics and Anatomical Correlates. Ophthalmic plastic and reconstructive surgery Shriver, E. M., Erickson, B. P., Kossler, A. L., Tse, D. T. 2016; 32 (5): 378-385


    To highlight features of lateral canthal tendon disinsertion (LCTD), provide an algorithm for systematic assessment, and describe the anatomic genesis of signs and symptoms.Retrospective case series of consecutive patients with lateral canthal tendon disinsertion, who underwent lateral canthal tendon fixation by a single surgeon (DTT) between 2004 and 2011.One hundred and seventeen eyes in 90 patients underwent lateral canthal tendon fixation. Average age was 69.3 ± 17.9 years. Twenty-three percentage of eyes had undergone lower eyelid blepharoplasty and 52% had undergone lateral canthal tightening; 35% had no previous periocular surgery. Patients with purely involutional lateral canthal tendon disinsertion were significantly older (76.1 ± 7.8 years of age; p < 0.03). Six key features associated with lateral canthal tendon disinsertion were identified. On static evaluation: 1) a blunted or vertically displaced lateral canthal angle; 2) a narrow horizontal fissure with reduced temporal scleral triangle; and 3) pseudo eyelid retraction. On dynamic evaluation with attempted closure: 4) medial and inferior movement of the lateral commissure; 5) incomplete apposition of the eyelid margins in the absence of anterior lamellar shortage; and 6) temporal eyelid imbrication. Improved blink dynamics with manual lateral canthal tendon complex repositioning ("the thumb test") predicted a favorable outcome with surgical tightening in 95.7% of cases.Lateral canthal tendon disinsertion results in altered eyelid fissure symmetry, blink dynamics, and lacrimal pump function. The authors recommend the mnemonic-A.B.C.: for Aperture configuration, Blink dynamics, and eyelid Closure-to structure the examination of all symptomatic patients. Manual restoration of the disinserted lateral canthal tendon with the "thumb test" predicts favorable outcomes with surgical fixation.

    View details for DOI 10.1097/IOP.0000000000000552

    View details for PubMedID 26398240

  • The Locking Y Lateral Canthopexy With Osseous Integration: Clinical Experience and Surgical Technique. Ophthalmic plastic and reconstructive surgery Kossler, A. L., Erickson, B. P., Shriver, E. M., Tse, D. T. 2016; 32 (5): 386-392


    To describe a surgical technique to correct lateral canthal tendon disinsertion with a strabismus surgery-inspired locking capture of the tendon complex and osseous integration via drill holes.Retrospective interventional case series including all patients with lateral canthal tendon disinsertion who underwent locking Y lateral canthopexy with drill hole reinforcement by 1 surgeon (D.T.T.) between 2006 and 2011. Outcome measures included resolution of presenting ocular symptoms, improved blink dynamics and lid closure, correction of lagophthalmos and exposure keratopathy, and need for further surgery.A total of 53 lateral canthopexies with osseous integration were performed in 42 patients who fulfilled clinical criteria for lateral canthal tendon disinsertion. The population was biased toward treatment failures; 81% of eyes (43/53) had a history of prior lateral canthal tightening, and of these 30.2% (16/53) had undergone 3 or more procedures. Postoperatively, all eyes demonstrated improved eyelid position and blink mechanics, and 83% (44/53) had subjective resolution of epiphora and ocular irritation. Lagophthalmos was fully corrected in 95% (19/20) of cases, and corneal staining resolved in 88% (14/16). With a mean follow-up period of 24 months, 3.7% of eyes (2/53) required additional lateral canthal tightening.The locking Y lateral canthopexy is an effective and durable method for repositioning the lateral canthal tendon complex to improve blink dynamics, eyelid closure, and cosmesis. Even in a population heavily biased toward treatment failure, clinical results are excellent and the reoperation rate is low.

    View details for DOI 10.1097/IOP.0000000000000553

    View details for PubMedID 26359700

  • Electronic enhancement of tear secretion. Journal of neural engineering Brinton, M., Chung, J. L., Kossler, A., KooK, K. H., Loudin, J., Franke, M., Palanker, D. 2016; 13 (1): 016006-?


    To study electrical stimulation of the lacrimal gland and afferent nerves for enhanced tear secretion, as a potential treatment for dry eye disease. We investigate the response pathways and electrical parameters to safely maximize tear secretion.We evaluated the tear response to electrical stimulation of the lacrimal gland and afferent nerves in isofluorane-anesthetized rabbits. In acute studies, electrical stimulation was performed using bipolar platinum foil electrodes, implanted beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve. Wireless microstimulators with bipolar electrodes were implanted beneath the lacrimal gland for chronic studies. To identify the response pathways, we applied various pharmacological inhibitors. To optimize the stimulus, we measured tear secretion rate (Schirmer test) as a function of pulse amplitude (1.5-12 mA), duration (0.1-1 ms) and repetition rate (10-100 Hz).Stimulation of the lacrimal gland increased tear secretion by engaging efferent parasympathetic nerves. Tearing increased with stimulation amplitude, pulse duration and repetition rate, up to 70 Hz. Stimulation with 3 mA, 500 μs pulses at 70 Hz provided a 4.5 mm (125%) increase in Schirmer score. Modulating duty cycle further increased tearing up to 57%, compared to continuous stimulation in chronically implanted animals (36%). Ethmoid (afferent) nerve stimulation increased tearing similar to gland stimulation (3.6 mm) via a reflex pathway. In animals with chronically implanted stimulators, a nearly 6 mm increase (57%) was achieved with 12-fold less charge density per pulse (0.06-0.3 μC mm(-2) with 170-680 μs pulses) than the damage threshold (3.5 μC mm(-2) with 1 ms pulses).Electrical stimulation of the lacrimal gland or afferent nerves may be used as a treatment for dry eye disease. Clinical trials should validate this approach in patients with aqueous tear deficiency, and further optimize electrical parameters for maximum clinical efficacy.

    View details for DOI 10.1088/1741-2560/13/1/016006

    View details for PubMedID 26655141

  • Objective surgical assessments for residents and experienced surgeons in the Yelp Era JOURNAL OF CATARACT AND REFRACTIVE SURGERY Cremers, S. L., Kossler, A. L., Ciolino, J., Henderson, B. A. 2015; 41 (11): 2593-2595

    View details for Web of Science ID 000368051300035

    View details for PubMedID 26703521

  • Implanted Microelectronic Stimulator Increases Tear Secretion in Rabbits Brinton, M., Chung, J., Kossler, A., Kook, K., Loudin, J., Ta, C., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2015
  • Neurostimulation of the lacrimal nerve for enhanced tear production. Ophthalmic plastic and reconstructive surgery Kossler, A. L., Wang, J., Feuer, W., Tse, D. T. 2015; 31 (2): 145-151


    To design a proof-of-concept study to assess the effect of lacrimal nerve stimulation (LNS) with an implantable pulse generator (IPG) to increase aqueous tear production.Experimental animal study design of 6 Dutch Belted rabbits. Ultra high-resolution optical coherence tomography (UHR-OCT) quantified tear production by measuring the baseline tear volume of each rabbit's OD and OS. A neurostimulator was implanted adjacent to the right lacrimal nerve. After 2 minutes of LNS (100 μs, 1.6 mA, 20 Hz, 5-8 V), the tear volumes were measured with UHR-OCT. The change in tear volume was quantified and compared with the nonstimulated OS. Three rabbits underwent chronic LNS (100 μs, 1.6 mA, 10 Hz, 2 V) and their lacrimal glands were harvested for histopathologic analysis.The UHR-OCT imaging of the OD tear volume showed a 441% average increase in tear production after LNS as a percent of baseline. After stimulation, OD had statistically significant greater increase in tear volumes than OS (p = 0.028, Wilcoxon test). Poststimulation OD tear volumes were significantly greater compared with baseline (p = 0.028, Wilcoxon test). Histopathologic examination of the lacrimal glands showed no discernible tissue damage from chronic neurostimulation. In addition, there were no gross adverse effects on the general well-being of the animals due to chronic stimulation.LNS with an IPG appears to increase aqueous tear production. Chronic LNS showed no histopathologic lacrimal gland damage. This study suggests that LNS is a promising new treatment strategy to increase aqueous tear production.

    View details for DOI 10.1097/IOP.0000000000000234

    View details for PubMedID 25126767

    View details for PubMedCentralID PMC4329098

  • Electrical Stimulation of the Lacrimal Gland in Rabbits Brinton, M., Chung, J., Kossler, A., Loudin, J., Ta, C., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2014
  • Author reply. Ophthalmology Tse, D. T., Kossler, A. L., Feuer, W. J., Benedetto, P. W. 2014; 121 (1): e8-e10

    View details for DOI 10.1016/j.ophtha.2013.11.012

    View details for PubMedID 24268860

  • Long-Term Outcomes of Neoadjuvant Intra-arterial Cytoreductive Chemotherapy for Lacrimal Gland Adenoid Cystic Carcinoma. Ophthalmology Tse, D. T., Kossler, A. L., Feuer, W. J., Benedetto, P. W. 2013


    PURPOSE: To compare the long-term outcomes after intra-arterial cytoreductive chemotherapy (IACC) with conventional treatment for lacrimal gland adenoid cystic carcinoma (ACC). DESIGN: Retrospective case series. PARTICIPANTS: Nineteen consecutive patients treated with IACC, followed by orbital exenteration, chemoradiotherapy, and intravenous chemotherapy. INTERVENTIONS: Analyses of the histologic characteristics of biopsy specimens, extent of disease at the time of diagnosis, diagnostic surgical procedures, incidence of locoregional recurrences or distant metastases, disease-free survival time, response to IACC, tumor margins at definitive surgery, and toxicity and complications. MAIN OUTCOME MEASURES: Disease relapse, disease-free survival, and chemotherapeutic complications. RESULTS: Eight patients with an intact lacrimal artery had significantly better outcomes for survival (100% vs. 28.6% at 10 years), cause-specific mortality, and recurrences (all P = 0.002, log-rank test) than conventionally treated patients from the University of Miami Miller School of Medicine. These 8 patients (group 1) had cumulative 10-year disease-free survival of 100% compared with 50% for 11 patients (group 2) who had an absence of the lacrimal artery or deviated from the treatment protocol (P = 0.035) and 14.3% for conventionally treated patients (P<0.001). Likewise, group 2 was associated with lower cause-specific mortality than the institutional comparator group (P = 0.038). Prior tumor resection with lateral wall osteotomy, delay in IACC implementation or exenteration, and failure to adhere to protocol are risk factors for suboptimal outcomes. CONCLUSIONS: Neoadjuvant IACC seems to improve overall survival and decrease disease recurrence. An intact lacrimal artery, no disruption of bone barrier or tumor manipulation other than incisional biopsy, and protocol compliance are factors responsible for favorable outcomes. The chemotoxicity complication rate is limited and manageable. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    View details for DOI 10.1016/j.ophtha.2013.01.027

    View details for PubMedID 23582989

  • Hordeolum, Chalazion and Blepharitis Primary Care: A Collaborative Practice Kossler, A., Banta, J. edited by Buttaro, T. M., Trybulski, J., Bailey, P. P., Sandberg-Cook, J. Mosby. 2012; 4th
  • Dacryocystitis and Nasolacrimal Duct Obstruction Primary Care: A Collaborative Practice Kossler, K. L., Banta, J. edited by Buttaro, T. M., Bailey, P. P., Trybulski, J., Sandberg-Cook, J. Mosby. 2012
  • Pediatric Cataract Ophthalmic Surgical Procedures Cremers, S., Lora-Kossler, A., Azar, N. edited by Hersh, P. S., Zagelbaum, B., Cremers, S. Thieme. 2009; 2nd
  • Time Domain versus Spectral Domain Optical Coherence Tomography (OCT) in the Diagnosis and Treatment of Angioid Streaks Ophthalmology Web Lora-Kossler, A. 2008
  • Conjunctival Squamous Cell Carcinoma with Intraocular and Intraorbital Invasion Ophthalmology Times Lora-Kossler, A., Johnson, T. 2008
  • Systemic Multiple Myeloma with Secondary Orbital Plasmacytoma Ophthalmology Times Andrea, L. 2008
  • Global Rating Assessment of Skills in Intraocular Surgery (GRASIS) OPHTHALMOLOGY Cremers, S. L., Lora, A. N., Ferrufino-Ponce, Z. K. 2005; 112 (10): 1655-1660


    The American Board of Ophthalmology in conjunction with the Accreditation Council for Graduate Medical Education has mandated the systematic assessment of surgical competence of ophthalmology residents at all residency programs. We present a tool complementary to the Objective Assessment of Skills in Intraocular Surgery (OASIS) to assess residents' surgical competence.Twenty experts in resident education, including the chiefs of all ophthalmology services and the chief resident at the Harvard Medical School Department of Ophthalmology.A 1-page subjective evaluation form was developed in conjunction with the Objective Assessment of Skills in Intraocular Surgery evaluation form to assess the surgical skills of residents. A panel of surgeons at the Harvard Medical School Department of Ophthalmology at the Massachusetts Eye and Ear Infirmary reviewed the form and provided constructive feedback.Experts' comments were incorporated, establishing face and content validity.The Global Rating Assessment of Skills in Intraocular Surgery (GRASIS) has face and content validity. It can be used to assess a resident's surgical care of patients as well as a resident's surgical knowledge, preparedness, and interpersonal skills. Reliability and predictive validity will be determined at our institution. We believe the GRASIS evaluation form will be a valuable tool in conjunction with the OASIS evaluation form for assessing ophthalmology residents' surgical skills at other residency programs as well.

    View details for DOI 10.1016/j.ophtha.2005.05.010

    View details for Web of Science ID 000232299200003

    View details for PubMedID 16102834

  • Impact of Depressive Illness on Emergency Department Recidivism: A New Approach to the “Frequent Flyer” Annals of Emergency Medicine Lora-Kossler, A., Simpsom, M., Freed, M., Milzman, D. 2004; 23 (44.4)
  • Effects of monocular viewing and eye dominance on spatial attention BRAIN Roth, H. L., Lora, A. N., Heilman, K. M. 2002; 125: 2023-2035


    Observations in primates and patients with unilateral spatial neglect have suggested that patching of the eye ipsilateral to the injury and contralateral to the neglected space can sometimes improve attention to the neglected space. Investigators have generally attributed the effects of monocular eye patching to activation of subcortical centers that interact with cortical attentional systems. Eye patching is thought to produce preferential activation of attentional systems contralateral to the viewing eye. In this study we examined the effect of monocular eye patching on attentional biases in normal subjects. When normal subjects bisect vertical (radial) lines using both eyes, they demonstrate a far attentional bias, misbisecting lines away from their body. In a monocular viewing experiment, we found that the majority of subjects, who were right eye dominant, had relatively nearer bisections and a diminished far bias when they used their right eye (left eye covered) compared with when they used their left eye (right eye covered). The smaller group of subjects who were left eye dominant had relatively nearer bisections and a diminished far bias when they used their left eye compared with when they used their right eye. In the hemispatial placement experiment, we directly manipulated hemispheric engagement by having subjects perform the same task in right and left hemispace. We found that right eye dominant subjects had a diminished far bias in right hemispace relative to left hemispace. Left eye dominant subjects showed the opposite pattern and had a diminished far bias in left hemispace. For both groups, spatial presentation affected performance more for the non-dominant eye. The results suggest that monocular viewing is associated with preferential activation of attentional systems in the contralateral hemisphere, and that the right hemisphere (at least in right eye dominant subjects) is biased towards far space. Finally, the results suggest that the poorly understood phenomenon of eye dominance may be related to hemispheric specialization for visual attention.

    View details for Web of Science ID 000177504900010

    View details for PubMedID 12183348

  • Pseudoprogression of Metastatic Melanoma to the Orbit With Pembrolizumab. Ophthalmic plastic and reconstructive surgery Garcia, G. A., Topping, K. L., Mruthyunjaya, P. n., Kossler, A. L. ; 36 (2): e36–e40


    The management of metastatic melanoma to the orbit may involve a variety of therapeutic modalities including external-beam radiation, chemotherapy, and varying degrees of surgical resection or debulking. Pembrolizumab is an immunotherapeutic agent that has demonstrated efficacy in the treatment of metastatic melanoma. The authors present a case of metastatic melanoma to the orbit demonstrating profound pseudoprogression within hours of beginning pembrolizumab therapy, with associated mass effect and vision loss. Systemic corticosteroids, orbital external-beam radiation therapy, and a brief interruption in pembrolizumab halted expansion of the orbital lesion and vision loss. This case illustrates that rapid increase in orbital melanoma size, due to acute inflammatory response, may occur after initiation of systemic pembrolizumab therapy. Clinicians should be aware of this pseudoprogression mechanism as a potential cause of vision compromise in metastatic orbital melanoma. Prompt recognition and treatment may be needed to prevent permanent vision loss.

    View details for DOI 10.1097/IOP.0000000000001543

    View details for PubMedID 32134764