Brent Hayek

Teprotumumab for thyroid-associated ophthalmopathy

BACKGROUND Thyroid‐associated ophthalmopathy, a condition commonly associated with Graves’ disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin‐like growth factor I receptor (IGF‐IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS We conducted a multicenter, double‐masked, randomized, placebo‐controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF‐IR, in patients with active, moderate‐to‐severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid‐associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves’ ophthalmopathy–specific quality‐of‐life questionnaire. Adverse events were assessed. RESULTS In the intention‐to‐treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug‐related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997.)

Clinical outcomes of radiotherapy as initial local therapy for Graves’ ophthalmopathy and predictors of the need for post-radiotherapy decompressive surgery

BackgroundThe optimal initial local treatment for patients with Graves’ ophthalmopathy (GO) is not fully characterized. The purpose of this retrospective study is to describe the clinical outcomes of RT as initial local therapy for GO and define predictors of the need for post-RT salvage bony decompressive surgery.Methods91 patients with active GO and without prior surgery were treated with RT as initial local therapy between 01/1999 and 12/2010, with a median follow-up period of 18.3 months (range 3.7 - 142 months). RT dose was 24 Gy in 12 fractions. 44 patients (48.4%) had prior use of steroids, with 31 (34.1%) being on steroids at the initiation of RT. The most common presenting symptoms were diplopia (79%), proptosis (71%) and soft tissue signs (62%).Results84 patients (92.3%) experienced stabilization or improvement of GO symptoms. 58 patients (64%) experienced improvement in their symptoms. 19 patients (20.9%) underwent salvage post-RT bony decompressive surgery. Smoking status and total symptom score at 4 months were independent predictors of post-RT bony decompression with odds ratios of 3.23 (95% CI 1.03 – 10.2) and 1.59 (95% CI 1.06 – 2.4), respectively. Persistent objective vision loss at 4 months post-RT was the most important symptom type in predicting salvage decompression. Chronic dry eye occurred in 9 patients (9.9%) and cataracts developed in 4 patients (4.4%).ConclusionsRT is effective and well tolerated as initial local therapy for active GO, with only 21% of patients requiring decompressive surgery post RT. Most patients experience stabilization or improvement of GO symptoms, but moderate to significant response occurs in the minority of patients. Smoking status and total symptom severity at 4 months, primarily persistent objective vision loss, are the primary determinants of the need for post-RT salvage bony decompression. Patients who smoke or present with predominantly vision loss symptoms should be advised as to their lower likelihood of symptomatic response to RT and their increased likelihood of requiring post-RT decompressive surgery.

Acellular dermal graft (AlloDerm) for upper eyelid reconstruction after cancer removal

Purpose: To report the use of AlloDerm for reconstruction of large upper eyelid defects in cancer patients. Methods: The clinical records of all patients who had AlloDerm as part of their upper eyelid reconstruction between July 2005 and July 2006 at a single institution were reviewed. Functional and cosmetic outcomes and postoperative complications were assessed. Results: Two patients had recurrent sebaceous gland carcinoma, 2 had melanoma, and 1 had squamous cell carcinoma. The upper eyelid defect involved the full thickness and entire width of the upper eyelid in 4 patients and full thickness and two thirds of the upper eye eyelid in 1 patient. The reconstructive procedure included a modified Cutler-Beard procedure using AlloDerm as the posterior lamellar sandwich graft in all 5 patients. One patient had early postoperative adjuvant radiation therapy to the upper eyelid. Three patients had excellent functional and cosmetic outcome; 2 patients had satisfactory outcomes. Two patients had residual exposure keratopathy. Allergic reaction to AlloDerm, infectious transmission, and immunologic rejection were not encountered at the time of this report (mean follow-up time = 13 months). Conclusions: AlloDerm can be used as an alternative sandwich graft material to replace the tarsus for reconstruction of large upper eyelid defects using a modified Cutler-Beard procedure.

Bilateral Lacrimal Gland Disease: Clinical Features of 97 Cases

OBJECTIVE Bilateral lacrimal gland (LG) disease is a unique presentation that can result from varied causes. We reviewed the diagnoses, clinical features, and outcomes of 97 patients with this entity. DESIGN Case series. PARTICIPANTS Ninety-seven patients with bilateral LG disease. METHODS Retrospective review and statistical analysis using analysis of variance and the Fisher exact test. MAIN OUTCOME MEASURES Patient demographics, clinical features, diagnostic testing, diagnosis, and treatment. RESULTS Patient age ranging from 8 to 84 years (mean, 46 years). The predominant gender was female (77%), and race included black (49%), white (38%), and Hispanic (12%) patients. Diagnoses fell into 4 categories: inflammatory (n = 51; 53%), structural (n = 20; 21%), lymphoproliferative (n = 19; 20%), and uncommon (n = 7; 7%) entities. The most common diagnoses included idiopathic orbital inflammation (IOI; n = 29; 30%), sarcoidosis (n = 19; 20%), prolapsed LG (n = 15; 15%), lymphoma (n = 11; 11%), lymphoid hyperplasia (n = 8; 8%), and dacryops (n = 5; 5%). Inflammatory conditions were more likely in younger patients (P<0.05) and in those with pain (P<0.001) and mechanical blepharoptosis (P<0.01) at presentation, whereas lymphoma was more common in older patients (P<0.001) without active signs of inflammation at presentation. Black patients were more likely to have sarcoidosis (P<0.01). Laboratory results showed high angiotensin converting enzyme level being significantly more likely in patients with sarcoidosis (P<0.05). However, sensitivity was limited to 45%, with 25% of patients diagnosed with IOI also demonstrating positive results. Corticosteroid therapy was the treatment of choice in 38 cases, corresponding to resolution of symptoms in 29% and improvement in an additional 32%. Overall, chronic underlying disease was found in 71% of patients, among whom 26% achieved a disease-free state, whereas 3% succumbed to their underlying disease. CONCLUSIONS The cause of bilateral lacrimal gland disease most commonly was inflammatory, followed by structural and lymphoproliferative. Patient characteristics and clinical presentations were key features distinguishing between competing possibilities. Despite local control with corticosteroids or radiotherapy, underlying disease continued in 71% of patients and led to death in 3%.

Ophthalmic Manifestations and Causes of Vision Impairment in Ebola Virus Disease Survivors in Monrovia, Liberia.

PURPOSE To describe the ocular findings, visual impairment, and association of structural complications of uveitis with visual impairment in a cohort of survivors of Ebola virus disease (EVD) in Monrovia, Liberia. DESIGN Retrospective, uncontrolled, cross-sectional study. PARTICIPANTS Survivors of EVD who were evaluated in an ophthalmology clinic at Eternal Love Winning Africa (ELWA) Hospital in Monrovia, Liberia. METHODS A cohort of EVD survivors who underwent baseline ophthalmic evaluation at ELWA Hospital were retrospectively reviewed for demographic information, length of Ebola treatment unit (ETU) stay, visual acuity (VA), and ophthalmic examination findings. For patients with uveitis, disease activity (active vs. inactive) and grade of inflammation were recorded according to Standardization of Uveitis Nomenclature criteria. The level of VA impairment was categorized according to World Health Organization classification for VA impairment as follows: normal/mild, VA 20/70 or better; moderate, VA 20/70-20/200; severe, VA 20/200-20/400; blindness, VA <20/400. Visual acuity, length of ETU stay, and structural complications were compared between EVD survivors with and without uveitis. Structural complications associated with moderate VA impairment or poorer were analyzed. MAIN OUTCOME MEASURES Frequency of ocular complications including uveitis and optic neuropathy in EVD survivors, level of VA impairment in EVD survivors with uveitis, and structural complications associated with VA impairment in EVD survivors. RESULTS A total of 96 survivors of EVD were examined. A total of 21 patients developed an EVD-associated uveitis, and 3 patients developed an EVD-associated optic neuropathy. Visual acuity was blind (VA >20/400) in 38.5% of eyes with uveitis. Anatomic subtypes of uveitis included anterior, posterior, and panuveitis in 2, 13, and 6 patients, respectively. Examination findings associated with at least moderate visual impairment by World Health Organization criteria (VA <20/70) included keratic precipitates (P < 0.002), posterior synechiae (P < 0.002), vitritis (P < 0.005), and chorioretinal scars (P < 0.02). CONCLUSIONS Survivors of EVD are at risk for uveitis, which may lead to secondary structural complications, visual impairment, and blindness. Eye care resources should be mobilized for EVD survivors in West Africa because of the frequency of this spectrum of disease complication and its potential for severe VA impairment and blindness.

Association of Clinical Response and Long-term Outcome Among Patients With Biopsied Orbital Pseudotumor Receiving Modern Radiation Therapy

PURPOSE To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). METHODS AND MATERIALS Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without an increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). RESULTS Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥ PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤ 46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. CONCLUSIONS RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors.

Optic nerve lymphoma: Report of two cases and review of the literature

Lymphoma may involve the optic nerve as isolated optic nerve lymphoma or in association with central nervous system (CNS) or systemic lymphoma. We present two biopsy-proven non-Hodgkin lymphomas of the optic nerve and compare our findings with previously reported cases. We discuss the mechanism of metastasis, classification of optic nerve involvement, clinical features, radiologic findings, optic nerve biopsy indications and techniques, histologic features, and treatments. We propose a classification system of optic nerve lymphoma: isolated optic nerve involvement, optic nerve involvement with CNS disease, optic nerve involvement with systemic disease, and optic nerve involvement with primary intraocular lymphoma. Although it is an uncommon cause of infiltrative optic neuropathy, optic nerve metastasis should be considered in patients with a history of lymphoma. The recommended approach to a patient with presumed optic nerve lymphoma includes neuroimaging and cerebrospinal fluid evaluation as part of the initial workup, then judicious use of optic nerve biopsy, depending on the clinical situation.

Viability of full-thickness skin grafts used for correction of cicatricial ectropion of lower eyelid in previously irradiated field in the periocular region

The purpose of this study was to evaluate the viability of skin grafts used for correction of cicatricial ectropion resulting from previous ablative surgery and radiotherapy for head and neck cancer and to report overall outcomes of cicatricial ectropion repair.

Dilated Superior Ophthalmic Vein: Clinical and Radiographic Features of 113 Cases.

PURPOSE Dilated superior ophthalmic vein (SOV) is an uncommon radiographic finding. The authors review the presentation, etiology, radiography, and visual implications of 113 patients with dilated SOV. METHODS An observational case series and multicenter retrospective chart review were conducted. There were 113 patients with a dilated SOV. Outcome measures included patient demographics, clinical features, radiographic findings, diagnosis, and treatment, and treatment outcomes were assessed. RESULTS Cases included 75 women (66%) and 38 men (34%) with a mean age of 49 ± 24 years (range, 0.4-90 years). Diagnoses fell under 6 categories: vascular malformation (n = 92, 81%), venous thrombosis (n = 11, 10%), inflammatory (n = 6, 5%), traumatic hemorrhage (n = 2, 2%), lymphoproliferative (n = 1, 1%), and infectious (n = 1, 1%). Imaging modalities utilized included MRI (n = 98, 87%), digital subtraction angiography (n = 77, 68%), CT (n = 29, 26%), and ultrasonography (n = 4, 4%). Disease status at last follow up included no evidence of disease (n = 57, 50%), alive with persistent disease (n = 53, 47%), and expired from disease (n = 3, 3%). Treatment and management was tailored to the underlying disease process with a mean follow up of 18 months (range, 1 day to 180 months). Visual impairment observed at presentation and last follow up across all cases was 26% and 22%, respectively. CONCLUSION Dilated SOV is a rare radiographic finding resulting from a wide spectrum of etiologies with clinical implications ranging from benign to sight- and life-threatening. Dilated SOV is most often found with dural-cavernous fistula or carotid-cavernous fistula, orbital or facial arteriovenous malformation, and venous thrombosis. Recognition of this finding and management of the underlying condition is critical.

Cutaneous melanoma metastatic to the eyelid and periocular skin.

Purpose: To report the clinical and histopathologic features in 6 patients with cutaneous melanoma metastatic to the eyelid and periocular skin. Methods: Clinical records and radiographic features of all consecutive patients treated by the principal investigator between January 2005 and October 2007 with the diagnosis of cutaneous melanoma metastatic to the eyelid and periocular skin. Results: Six patients ranged in age from 26 to 84 years old (median, 55 years). Five patients had their metastatic lesion in the upper eyelid and 1 in the lower eyelid. The mean survival after the diagnosis of melanoma metastatic to the eyelid was 5.3 months. All patients had metastases at other sites detected prior to the diagnosis of the eyelid metastasis. The mean interval from initial primary tumor diagnosis to metastasis to the eyelid was 121 months. In all 6 patients, palliative surgical resection of the metastatic eyelid lesions was carried out. Conclusions: Melanoma metastatic to the eyelid is not uncommon in advanced stage cutaneous melanoma. Palliative surgical management of these metastatic lesions should be considered to improve the patients quality of life.