Bilateral primary orbital xanthogranulomas: A case report and comparison of xanthomatous conditions.

This report describes an unusual and diagnostically challenging case of subcutaneous soft tissue xanthogranulomas of bilateral orbits of a 58-year-old female patient seen in a private oculoplastics practice. Accurate and timely diagnosis is crucial in xanthogranulomatous diseases so that any systemic manifestations can be identified and addressed in a multidisciplinary fashion. Periorbital xanthogranuloma is a frequent early manifestation of adult xanthogranulomatous disease, and its association with life-threatening systemic disease requires accurate diagnosis and prompt work-up. This case describes an otherwise asymptomatic patient who presented with bilateral orbital masses causing visually significant ptosis, initially diagnosed as soft tissue xanthomas, and later identified as xanthogranulomas. It is important for physicians of all fields, from primary care to surgical subspecialty, to be aware that xanthogranulomatous disease may first present as periorbital lesions and/or orbital masses, and that further work-up for vision and life-threatening systemic disease is warranted.

Idiopathic sclerosing dacryoadenitis.

Dacryoadenitis is an inflammation of the lacrimal gland. This condition has an extensive differential diagnosis, requiring a thorough workup to identify the underlying etiology. If no etiology is identified, the condition is termed idiopathic dacryoadenitis. The purpose of this report is to present a case of idiopathic sclerosing dacryoadenitis and review the diagnostic process.We present a case of sclerosing dacryoadenitis non responsive to systemic antibiotics and steroids, improving after surgical debulking/biopsy. Systemic inflammatory and infectious labs were negative. Tissue was negative for SARS-CoV-2 antigen. Histopathologic review of the surgical specimen revealed nonspecific, sclerosing dacryoadenitis, ultimately supporting the diagnosis of idiopathic nonspecific fibrosing dacryoadenitis.This case reviews the presentation, evaluation, and management of a common orbital pathologic condition, with updated recommendations based on the most current literature.

Cannabidiol as an Adjunct to Botulinum Toxin in Blepharospasm - A Randomized Pilot Study.

Purpose: The purpose of this study was to evaluate the safety and efficacy of low dose cannabidiol (CBD; Epidiolex) as adjunctive therapy for idiopathic adult-onset blepharospasm (BPS), as well as develop a novel objective assessment methodology to gauge response. Methods: Prospective, randomized, double-masked, placebo-controlled crossover design of 6 months duration of 12 patients with BPS undergoing routine maximal botulinum toxin (BTX) therapy and experiencing breakthrough symptoms. Participants received their standard BTX every 3 months and were randomized to group A = CBD daily in cycle 1, followed by placebo in cycle 2 or group B = placebo followed by CBD. Videos recorded at days 0, 45, and 90 of each cycle were analyzed to quantify eyelid kinematics. The Jankovic Rating Scale (JRS) was used to provide a clinical rating. Results: All 12 patients completed the study without adverse events. CBD decreased median eyelid closure amplitude by 19.1% (-1.66 mm, confidence interval [CI] = -3.19 to -0.14 mm, P = 0.03), decreased median eyelid closure duration by 15.8% (-18.35 ms, CI = -29.37 to -7.32 ms, P = 0.001), and increased the maximum eyelid closure velocity by 34.8% (-13.26 mm/ms, CI = -20.93 to -5.58 mm/ms, P = 0.001). The JRS showed a 0.5 reduction in severity and frequency, which was not statistically significant. Conclusions: Low dose CBD was safely tolerated and improved several BPS kinematic parameters. The clinical scale suggested a direction of effect but may have been underpowered. Further studies are needed to better quantify the clinical relevance. Translational Relevance: This work describes a novel assessment methodology and therapeutic approach to bBPS.

Orbital lymphocyte populations in three states of thyroid eye disease.

Purpose: We report histopathologic orbital tissue analysis from three patients with thyroid eye disease (TED) - active, chronic, and post-teprotumumab to better characterize orbital cellular populations in these varying states of TED. Observations: Orbital tissues in TED demonstrate minimal lymphocytic infiltration in fat and Mueller's muscle. Following teprotumumab treatment, the tissues were devoid of lymphocytes with only perivascular cuffs of T-lymphocytes remaining in orbital fat. Conclusions and importance: In active TED, post-teprotumumab treatment, and in quiescent TED, orbital fat may not show significant inflammatory infiltration. More work is warranted to characterize specific cellular effects of teprotumumab and other biologics.

The Role of Insulin-like Growth Factor-1 and Its Receptor in the Eye: A Review and Implications for IGF-1R Inhibition.

PURPOSE: FDA approval of teprotumumab for thyroid eye disease in January 2020 reinforced interest in the pharmacologic potential of insulin-like growth factor-1 (IGF-1) and its receptor, IGF-1R. Despite recent approval and adaptation for ophthalmic use, IGF-1R inhibitors are not a new therapeutic class. In 1986, Yamashita described aIR3, a monoclonal antibody to IGF-1R (anti-IGF-1R), that inhibited the effect of IGF-1 on growth hormone release. Given the widespread presence of IGF-1R, interrupting this receptor can lead to systemic physiologic effects, some adverse. We aim to review what is known about IGF-1/IGF-1R in the eye and consider the possible local side effects, unintended consequences, and potential uses of this medication class. METHODS: A PubMed database search utilizing the keywords "insulin-like growth factor-1, eye, inhibitor, antibody, side effect" was performed to identify publications discussing IGF-1 in the human eye from January 2011 to August 2021. Criteria for acceptance included studies discussing human subjects or human tissue specifically related to the eye. RESULTS: Out of a total of 230 articles, 47 were organized in 3 subject groups for discussion: thyroid-associated orbitopathy, cornea and the ocular surface, and the retina and neovascularization. Review of the literature demonstrated that IGF-1 affects growth and development of the eye, epithelial proliferation, retinal angiogenesis, inflammation, and is associated with thyroid-associated orbitopathy. CONCLUSIONS: IGF-1R exists throughout in the human body, including the cornea, retina, and orbit. Research regarding ocular effects of IGF-1/IGF-1R outside thyroid eye disease is limited. Carefully designed studies and clinical assessments of patients undergoing treatment with anti-IGF-1R may identify ocular side effects and foster consideration of the role of anti-IGF-1R in ocular therapeutics. Given the increasing use of anti-IGF-1R antibodies, understanding their ocular effects, side effects, and potential systemic implications for use in disease is critical.

IgG4-related disease presenting with profound bilateral orbital and adnexal inflammation.

Purpose: IgG4-related disease is an immune-mediated fibroinflammatory condition that can affect almost every major organ system. Orbital and adnexal involvement in IgG4-related disease though not uncommon can be varied depending on the site of the lymphoplasmacytic infiltration. This case of profound bilateral orbital inflammation is presented to demonstrate the significant clinical manifestations of IgG4-related ophthalmic disease. Observations: A 52-year-old man with a remote and seemingly unrelated history of lymphadenopathy presented to the Oculoplastics clinic with massive bilateral upper and lower lid swelling and induration. Hematologic testing demonstrated an elevation in serum IgG4 - a non-specific finding seen in various infectious, inflammatory, and malignant processes. Imaging demonstrated diffuse enlargement of orbital structures, including the lacrimal glands and extraocular muscles, as well as inflammatory changes of the adnexal and retrobulbar soft tissue. Orbital biopsy was required to confirm the diagnosis of IgG4-related ophthalmic disease. Conclusions and Importance: IgG4-related ophthalmic disease presents with various non-specific clinical signs and symptoms. The most common presentations include dacryoadenitis, enlarged orbital nerves, and orbital fat involvement; however, the extent of involvement both locally and systemically varies greatly. Clinical findings and imaging are helpful in narrowing the differential diagnosis; however, biopsy for histopathologic examination is essential to confirm IgG4-related disease. Physicians must maintain a high level of suspicion for the disease for proper management.

Revisiting the single-eyelid hughes reconstruction - A report of two cases.

Purpose: The reconstruction of near-total upper eyelid defects is challenging and complicated. There are multiple possible techniques, including multi-stage lower eyelid flaps (such as Mustarde's lid-switch flap and the Cutler-Beard techniques) as well as single-stage techniques with free grafts. Here we present two patients requiring near-total upper eyelid repairs that were accomplished by a single-eyelid, single-stage technique using a tarsoconjunctival flap. Observations: Two cases of near-total upper eyelid defects are described, one secondary to resection of a basal cell carcinoma and the other secondary to resection of a Merkel cell carcinoma. Both cases had sufficient residual tarsus to supply a single-eyelid tarsoconjunctival flap. Results were excellent. Conclusions: When there is sufficient tarsus remaining, the illustrated technique provides an excellent repair of near-total upper-eyelid defects. It is a simpler procedure than its alternatives, spares other tissue sites, eliminates free grafts, and does not require multiple stages.

Teprotumumab-associated chronic hearing loss screening and proposed treatments.

We report a case of a woman in her 50s with chronic teprotumumab-associated sensorineural hearing loss. The patient presented with chronic thyroid eye disease with proptosis and diplopia despite systemic thyroid control and orbital decompression. She was started on teprotumumab but developed tinnitus after the third dose, followed by frank hearing loss after the fifth dose. Her audiogram showed bilateral mild to moderate-severe hearing loss, which was significantly worse compared with her baseline audiogram obtained prior to treatment. Teprotumumab was immediately stopped, however repeat audiogram 6 weeks later showed no improvement. Given potentially irreversible sensorineural hearing loss, we recommend close monitoring with regular audiometric testing before, during and after teprotumumab therapy and propose potential treatment to reverse its effects in the ear.

A 'never miss' diagnosis: Ptosis secondary to metastatic breast cancer diagnosed as involutional ptosis and a review of the literature.

We present a case of ptosis secondary to metastatic lobular carcinoma of the breast which was initially diagnosed as involutional ptosis. A 67-year-old woman previously diagnosed with lobular carcinoma of the breast presented to our clinic with mild restriction of lateral gaze and persistent droopiness of her right eyelid (associated with decreased levator function) despite recent repair of a suspected involutional ptosis. Orbital magnetic resonance imaging revealed a mass in the right orbit which was biopsied and diagnosed as lobular carcinoma of the breast. Poor levator function is rarely present in involutional ptosis. Especially in conjunction with abnormal extraocular motility, other etiologies of acquired ptosis must be considered. This case highlights the importance of patient history and ocular examination in identifying the underlying etiology of ptosis. A review of the literature to evaluate the incidence of signs and symptoms associated with metastatic breast cancer to the orbit is included.

A case of ulcerative colitis associated with teprotumumab treatment for thyroid eye disease.

PURPOSE: To present a case of ulcerative colitis associated with teprotumumab treatment for thyroid eye disease. OBSERVATIONS: A 46-year-old Indian female was treated with teprotumumab (Tepezza) for severe thyroid eye disease within 9 months of diagnosis. The patient noted progression of her disease on oral prednisone and demonstrated severe, debilitating proptosis accompanied by eye ache and dry eyes. After 5 infusions of teprotumumab over a four-month period, the patient developed bloody diarrhea and fecal urgency. These symptoms progressively worsened and after two additional treatments, she underwent a colonoscopy. This confirmed the diagnosis of ulcerative colitis (UC). Treatment with teprotumumab was halted prior to the administration of the 8th infusion; however, the patient continued to have severe gastrointestinal symptoms two months after her last treatment. CONCLUSIONS AND IMPORTANCE: Teprotumumab is an insulin-like growth factor-1 receptor (IGF-1R) inhibitor demonstrated to improve proptosis in patients with active thyroid eye disease. Most adverse events reported are mild or moderate in severity; however, inflammatory bowel disease (IBD) is a serious adverse event that can develop as a result of treatment.

Increased incidence of chalazion associated with face mask wear during the COVID-19 pandemic.

PURPOSE: To determine whether the incidence of chalazion increased significantly in the San Francisco Bay Area and Los Angeles County following the widespread adoption of face mask wear in response to the COVID-19 pandemic. METHODS: This is a retrospective multicenter study of two ophthalmology institutions: a private Oculoplastics practice in San Francisco and the Oculoplastics division of the Stein Eye Institute at the University of California, Los Angeles. All patients seen during the studied time periods with a diagnosis of chalazion or hordeolum were identified through review of electronic medical records and included in the study. Incidence was determined for each month between January and August 2020, and compared to data from prior years via ANOVA to evaluate for changes after the onset of the pandemic. RESULTS: In San Francisco, the incidence of chalazion rose significantly in June through August of 2020 when compared to the same interval in 2016, 2017, 2018, and 2019. In Los Angeles, the rise in chalazion incidence in 2020 was also statistically significant when compared to data from the years 2018 and 2019. CONCLUSION: Importance: Widespread mask wear does appear to correspond to an increased incidence of chalazion. This risk may be minimized, while still maintaining the protective benefits of mask wear, by taking the proactive measures discussed to decrease mask induced eye dryness and changes in the eyelid microbiome.

Optical Device to Improve Eyelid Surgery.

Background. Obtaining symmetry is one of the most critical challenges of bilateral blepharoplasty surgery. Current techniques rely on caliper measurements and the "eye" of the surgeon. This is time-consuming and prone to error. There is a need for a precise and cost-effective surgical guide. Objective. The purpose of this experimental study was to design a device to improve the accuracy of markings in blepharoplasty. Methods. The device, a combination of a camera and pico-projector, creates a mirror image of the marked eye that is projected onto the second eye with a light beam. This allows the reference features in the captured image to be overlaid precisely on the respective features in the second eye. The device concept was tested initially on a mannequin and then on eleven human volunteer subjects. No actual surgeries were performed. The accuracy of the markings was assessed by comparing optical images of one eye to another via a specifically designed computer analysis. Results. The results of this study revealed that the accuracy of guided blepharoplasty markings was superior to that of unguided markings. Conclusion. The proposed device has a potential to improve precision of symmetrical surgical marking in blepharoplasty surgery, greatly reduce surgeon's time and effort, and ultimately contribute to successful patient outcomes and satisfaction. Additional modifications are forthcoming to prepare the device for clinical use.

Muir-Torre Syndrome Associated Periocular Sebaceous Neoplasms: Screening Patterns in the Literature and in Clinical Practice.

BACKGROUND: Muir-Torre syndrome (MTS) is defined clinically as the association of cutaneous sebaceous neoplasm and visceral malignancy. Ancillary tests are considered crucial for diagnosis. Although screening guidelines for MTS, including the Mayo MTS scoring system, have been proposed, there are no ophthalmic site-specific guidelines. SUMMARY: A literature review conducted by PubMed search for articles describing patients with periocular sebaceous neoplasm and MTS disclosed 31 publications describing 60 patients, 36 (60%) of whom fulfilled clinical criteria for MTS, 6 (10%) whose diagnosis was based on screening ancillary studies, 14 (23%) who fulfilled clinical criteria and had supporting screening ancillary studies, and 4 (7%) who fulfilled clinical criteria and had supporting diagnostic genetic testing. Most patients were male (34 vs. 15 females), with a median age of 59 years (range 37-79 years). The most common diagnosis was sebaceous carcinoma (40/60, 67%), followed by sebaceous adenoma (16/60, 27%), followed by other tumors with sebaceous differentiation (4/60, 6%). The periocular lesions were identified prior to visceral malignancy in 10 out of 45 (22%) cases, after visceral malignancy in 34 out of 45 (76%) cases, and concurrently with visceral malignancy in 1 out of 45 (2%) cases. Immunohistochemistry for mismatch repair proteins was performed in 41 out of 60 (68%) and 14 out of 38 (37%) of the tumors had lost MSH2. Based on Mayo-MTS scores of 2 or greater, and after removing visceral malignancies not included in their scoring algorithm, 26 out of 30 of patients (87%) with complete data were considered to be appropriate candidates for further work-up. A survey of current practice was conducted by questionnaires, distributed to ophthalmic pathologists, ocular oncologists, and oculoplastic surgeons from national and international professional societies. Of the 103 physicians who participated in the survey, 91 (88%) felt that MTS evaluation guidelines were not sufficiently clear. KEY MESSAGES: Our findings suggest that Mayo MTS screening guidelines may be applicable to periocular sebaceous neoplasms. The uncertainty of ophthalmic specialists about optimal screening guidelines for MTS reflects the heterogeneity of defining criteria for MTS and limited molecular genetic data. Larger studies with detailed clinical, histopathologic, and molecular genetic data are required to formally assess screening guidelines for MTS in patients with periocular sebaceous neoplasms.