A unique case of benign intermittent upbeat nystagmus triggered by light stimulation.

A 3-month-old girl with no past medical history presented with new-onset intermittent upbeat nystagmus. Episodes were triggered by movement into the supine position as well as by bright light flashes. They lasted a few seconds and were not associated with any distress. Neurological examination and work-up, including magnetic resonance imaging of the brain and abdominal ultrasonography, were normal. The eye movements completely resolved after 3 months.

Acute macular neuroretinopathy associated with acute promyelocytic leukemia.

PURPOSE: To describe the first reported case of acute macular neuroretinopathy (AMN) associated with acute promyelocytic leukemia in a young Asian-Indian male. OBSERVATIONS: We review the clinical and multimodal imaging findings in our patient that are characteristic of AMN. CONCLUSIONS AND IMPORTANCE: Ophthalmologists should be aware of the association of leukemia with AMN and consider hematologic work-up when assessing patients with AMN without the prototypical history or risk factors.

Impact of Food and Drug Administration Approval of Vismodegib on Prevalence of Orbital Exenteration as a Necessary Surgical Treatment for Locally Advanced Periocular Basal Cell Carcinoma.

PURPOSE: To test the hypothesis that the US Food and Drug Administration approval of vismodegib in early 2012 has reduced the prevalence of orbital exenteration for locally advanced periocular basal cell carcinoma (BCC). METHODS: Following institutional review board approval, the authors reviewed clinical and pathological data of patients with locally advanced periocular BCC (T4 per the eyelid carcinoma classification in the 8th edition of the AJCC Cancer Staging Manual) treated by the senior author during 2006-2018. Patients were grouped into those who were treated before February 2012 ("before vismodegib approval") and those who presented later ("after vismodegib approval"). RESULTS: Forty-two patients with locally advanced periocular BCC were treated during the study period, of whom 31 were men. The median age at presentation was 66 years (range, 43-90). Twenty-two patients had T4a and 20 had T4b tumors. Thirteen patients were treated before and 29 were treated after vismodegib approval. The 2 groups did not differ in age distribution (p = 0.164), sex distribution (p = 0.270), prevalence of recurrent tumor at presentation (p = 0.317), or duration of treatment with vismodegib (p = 0.605). Orbital exenteration was significantly more prevalent in patients treated before vismodegib approval than after (46% vs. 10%, p = 0.016), and vismodegib treatment was significantly more prevalent in patients treated after vismodegib approval than before (when vismodegib was given in clinical trials; 69% vs. 23%, p = 0.008). There was a trend toward more patients retaining their eyes at last follow-up in patients treated after vismodegib approval (83% vs. 54%, p = 0.066). CONCLUSIONS: The prevalence of orbital exenteration as a necessary surgical procedure in patients with a locally advanced periocular BCC has fallen since the Food and Drug Administration approval of vismodegib. Although vismodegib is not specifically approved for organ-sparing, it has changed the authors' practice and enabled eye preservation in patients with locally advanced periocular BCC, who would otherwise require an orbital exenteration.

Prevalence of a Histologic Change of Ocular Adnexal Lymphoma in Patients With a History of Lymphoma.

PURPOSE: The authors examined the prevalence of a histologic change of ocular adnexal lymphoma (OAL) grade in patients with a history of lymphoma in nonocular sites. METHODS: In this retrospective study, the authors reviewed the clinical and pathological data of 209 patients with OAL treated by the senior author during 2000 to 2017. RESULTS: Of 209 patients with OAL, 65 (31%) had a history of lymphoma. In 54 of the 65 patients (83%), the original lymphoma and OAL were of the same histologic type. In 8 of the 65 patients (12.3%), the OAL was more indolent than the original lymphoma: 6 patients with a history of diffuse large B-cell lymphoma, one of mantle cell lymphoma, and one of grade 3 follicular lymphoma had biopsy-proven extranodal marginal-zone lymphoma in the orbital area. Two additional patients (3%) with a history of chronic lymphocytic leukemia developed OAL: diffuse large B-cell lymphoma in one patient and extranodal marginal-zone lymphoma in the other. One patient (1.5%) with a history of a low-grade follicular lymphoma relapsed as a different low-grade histology of extranodal marginal-zone lymphoma. Lower-grade OAL than the original lymphoma was more common than higher-grade OAL than the original lymphoma (p = 0.048). CONCLUSIONS: In this cohort of 209 patients with OAL, the authors found that nearly one third had a history of lymphoma, 17% of whom had a different histologic type of lymphoma in the orbit, more commonly a more indolent type. This underscores the importance of biopsy of OAL even in patients with a known history of lymphoma to determine the histologic subtype of orbital lymphoma and to help guide appropriate treatment.

Extraocular Muscle Enlargement and Thyroid Eye Disease-like Orbital Inflammation Associated with Immune Checkpoint Inhibitor Therapy in Cancer Patients.

PURPOSE: To describe thyroid eye disease (TED)-like orbital inflammatory syndrome in 3 cancer patients treated with immune checkpoint inhibitors. METHODS: All consecutive patients treated by the senior author who were receiving immune checkpoint inhibitors and developed TED-like orbital inflammation were included. RESULTS: Three cancer patients treated with immune checkpoint inhibitors developed orbital inflammation. The first patient was treated with a combination of a cytotoxic T-lymphocyte antigen-4 inhibitor and a programmed cell death protein 1 inhibitor and developed TED-like orbital inflammation with normal thyroid function and antibody levels. The second patient had a previous diagnosis of Graves disease without TED, and developed TED soon after initiating treatment with a programmed cell death protein 1 inhibitor. The third patient developed acute hyperthyroidism with symptomatic TED following treatment with an investigational cytotoxic T-lymphocyte antigen-4 inhibitor agent. All 3 patients were managed with either systemic steroids or observation, with resolution of their symptoms and without the need to halt immune checkpoint inhibitor treatment for their cancer. DISCUSSION AND CONCLUSIONS: TED-like orbital inflammation may occur as a side effect of immune checkpoint inhibitor therapy with anti-cytotoxic T-lymphocyte antigen-4 or anti-PD-1 inhibitors. To the best of their knowledge, this is the first reported case of TED as a result of programmed cell death protein 1 inhibitor monotherapy. All 3 patients were treated with systemic steroids and responded quickly while continuing treatment with immune checkpoint inhibitors for their cancer. With increasing use of this class of drugs, clinicians should be familiar with the clinical manifestations and treatments for this adverse reaction.

Change in Eyelid Carcinoma T Category With Use of the 8th Versus 7th Edition of the American Joint Committee on Cancer: Cancer Staging Manual.

PURPOSE: To evaluate the frequency and nature of changes in T category when eyelid carcinomas are staged using the criteria in the 8th edition instead of the 7th edition of the American Joint Committee on Cancer staging manual. METHODS: Following Institutional Review Board approval, a retrospective review was conducted for all consecutive patients with the diagnosis of eyelid carcinoma treated by the senior author from January 2012 through December 2016. After a review of the clinical and pathologic data, each patient's disease was staged using both the 7th-edition and 8th-edition American Joint Committee on Cancer criteria for eyelid carcinomas. Changes in T categories between the 2 staging systems were examined. RESULTS: The review initially identified 167 patients with the diagnosis of eyelid carcinoma. Four patients were excluded because of incomplete or unclear data. The remaining 163 patients included 78 men and 85 women aged 21 to 97 years (median, 68 years). Eighty-two patients had basal cell carcinoma; 35, squamous cell carcinoma; 32, sebaceous carcinoma; 6, mucinous eccrine carcinoma; 3, Merkel cell carcinoma; 3, adenocarcinomas; and 2, adnexal carcinoma. The most common T category according to the 7th-edition criteria was T2a; the most common T category according to the 8th-edition criteria was T1b. Of the 163 patients, 64 (39%) had a lower T category with the 8th-edition than with the 7th-edition criteria, 59 (36%) had a higher T category, and 40 (25%) had the same T category. CONCLUSIONS: Application of the 8th-edition American Joint Committee on Cancer criteria for eyelid carcinoma changed the T category in 75% of patients. In general, the new 8th-edition American Joint Committee on Cancer tumor, node, metastasis (TNM) designations allow for a more objective and consistent designation of the T category.

Ocular preservation with neoadjuvant vismodegib in patients with locally advanced periocular basal cell carcinoma.

BACKGROUND/AIMS: Locally advanced (T4 per American Joint Committee on Cancer (AJCC) 8th edition) periocular basal cell carcinoma (BCC) can lead to loss of the eye. We report the neoadjuvant use of vismodegib followed by surgery in patients with such lesions with eye preservation as primary goal. METHODS: This retrospective interventional study includes all patients with a T4 periocular BCC (per 8th edition AJCC for eyelid carcinoma) treated by the senior author between 2013 and 2017 with neoadjuvant vismodegib prior to definitive surgery. RESULTS: Eight patients had a T4 tumour. Six patients presented with recurrent disease. Indications for neoadjuvant treatment were an unresectable tumour in one patient, an attempt to avoid an orbital exenteration in six patients and an attempt to avoid disfiguring facial surgery in one patient. Patients were treated for a median of 14 months (range: 4-36 months). All patients underwent an eye-sparing surgery following neoadjuvant vismodegib and all final surgical margins were negative for tumour. Five patients had a complete response to vismodegib with no microscopic residual BCC found during surgery; three patients had a significant partial response with residual tumour found on pathology. At last follow-up, a mean of 18 (range: 6-43) months after surgery, all patients were off-vismodegib and alive without evidence of disease. CONCLUSIONS: Neoadjuvant vismodegib for locally advanced (T4) periocular BCC enabled an eye-sparing surgery in all patients in our cohort. Prolonged treatment was well tolerated by most patients. Over half of patients achieved a complete response with no residual microscopic disease. Careful long-term follow-up is needed to confirm long-term disease-free survival.

Immunotherapy With Programmed Cell Death 1 Inhibitors for 5 Patients With Conjunctival Melanoma.

Importance: Conjunctival melanoma has the potential for regional lymphatic and distant metastasis. There is an urgent need for effective treatment for patients with metastatic or locally advanced conjunctival melanoma. Objective: To describe the use of immune checkpoint inhibitors for the treatment of conjunctival melanoma in 5 adult patients. Design, Setting, and Participants: A retrospective review was conducted of the medical records of 5 patients with conjunctival melanoma who were treated with immune checkpoint inhibitors from March 6, 2013, to July 7, 2017. Main Outcomes and Measures: Response to treatment and disease-free survival. Results: Of the 5 patients (4 women and 1 man) with metastatic conjunctival melanoma, 4 were treated with a programmed cell death 1 (PD-1) inhibitor, nivolumab, and had a complete response to treatment with no evidence of disease at 1, 7, 9, and 36 months after completing treatment. One patient with metastatic conjunctival melanoma was treated with another PD-1 inhibitor, pembrolizumab, and had stable metastases during the first 6 months of treatment. Later disease progression resulted in treatment cessation after 11 months and switching to another therapy. Two patients treated with nivolumab developed autoimmune colitis that necessitated stopping the immunotherapy; these patients subsequently were managed with systemic corticosteroids or infliximab. Conclusions and Relevance: This case series report suggests that anti-PD-1 therapy can be used to treat metastatic conjunctival melanoma. Longer follow-up is needed to determine the long-term disease-free survival. Future studies might assess the potential for immune checkpoint inhibitors to obviate the need for orbital exenteration in selected patients with locally advanced disease.

Desmoplastic Melanoma of the Periorbital Region.

Desmoplastic melanoma (DM) is a rare subtype of melanoma and an even smaller proportion of periocular melanomas. Here, the authors report 2 cases of DM in the periocular region. Staged according to the American Joint Committee on Cancer (AJCC) eighth edition classification, patient 1 presented with a stage IIIC (pT4apN1cM0) DM in the left lateral canthus with upper and lower eyelid and patient 2 presented with a stage IIIB (T4aN1bM0) DM in the left brow and supraorbital region with a parotid lymph node metastasis. In both patients, the lesions were amelanotic, with inflammatory appearance, and had been noted for several years before the correct diagnosis was made. In both patients, wide excision led to large surgical defects, and perineural invasion prompted adjuvant radiation therapy postoperatively. Patient 2 was treated with an immune checkpoint inhibitor for his parotid metastasis. Ophthalmologists should be aware of DM, its neurotrophic nature, and potential to metastasize with locally advanced lesions.

Rituximab Monotherapy Is Effective in Treating Orbital Necrobiotic Xanthogranuloma.

The authors report a case of a patient with bilateral orbital necrobiotic xanthogranuloma and no associated systemic paraproteinemia. Orbital biopsy showed strong expression of CD20-positive cells. The patient was treated with systemic rituximab monotherapy, with excellent clinical response and marked regression of the orbital lesions on imaging. At the time of writing, the patient has been treated with bimonthly rituximab maintenance therapy for 22 months and has stable clinical and imaging findings with sustained response to treatment and no reported side effects. To the authors' knowledge, this is the first reported case of orbital necrobiotic xanthogranuloma successfully treated with rituximab monotherapy. They hope that this well-documented case will encourage clinicians to consider rituximab monotherapy as a possible treatment option, albeit one entailing an off-label use of this drug, for patients with necrobiotic xanthogranuloma of the orbit.

Prognostic Value of the Staging System for Eyelid Tumors in the 7th Edition of the American Joint Committee on Cancer Staging Manual.

PURPOSE: To determine the prognostic value of the staging criteria for eyelid tumors in the 7th edition of the American Joint Committee on Cancer (AJCC) staging manual and to determine, for each type of eyelid tumor, which AJCC T categories are associated with increased risk of nodal metastasis and thus potential usefulness of sentinel lymph node biopsy. METHODS: Systematic review and analysis of articles found by searching PubMed and Google Scholar using the search terms "AJCC," "eyelid," "carcinoma," and "melanoma." RESULTS: Rates of local recurrence, regional nodal metastasis, and distant metastasis were approximately 7% to 10%, 1% to 9%, and 0% to 0.8%, respectively, for eyelid squamous cell carcinoma; 5% to 6%, 8% to 23%, and 2% and 14%, respectively, for eyelid sebaceous carcinoma; 10%, 10% to 22%, and 19% to 22%, respectively, for eyelid Merkel cell carcinoma (when staged according to the criteria for eyelid carcinoma as opposed to Merkel cell carcinoma), 14%, 5%, and 0%, respectively, for eyelid sweat gland carcinoma; and 2%, 9%, and 6%, respectively, for eyelid melanoma. Overall, the risks of local recurrence and regional nodal and distant metastasis appeared to increase with increasing AJCC T category, although not statistically significant in all studies. Clinical T2b or greater T category was significantly associated with increased risk of nodal metastasis for eyelid squamous cell carcinomas, sebaceous carcinomas, Merkel cell carcinomas (staged with eyelid carcinoma criteria), sweat gland carcinomas, and melanomas. Clinical T3 or greater T category was significantly associated with distant metastasis for eyelid carcinomas and melanomas. CONCLUSION: For eyelid carcinomas and eyelid melanomas, AJCC 7th edition T category correlates with the risks of nodal and distant metastasis, with T2b and larger tumors associated with highest risk of nodal metastasis. Patients with T2b or larger tumors may be candidates for sentinel lymph node biopsy or close nodal surveillance.

Immune Checkpoint Inhibitors for Treatment of Metastatic Melanoma of the Orbit and Ocular Adnexa.

Programmed cell death 1 (PD-1) inhibitors are members of a new class of drugs known as immune checkpoint inhibitors and have proven efficacy in the treatment of metastatic melanoma. Herein, the authors report the use of nivolumab and pembrolizumab, 2 recently Food and Drug Administration-approved PD-1 inhibitors, in 3 patients: 1 with metastatic conjunctival melanoma and 2 with metastatic cutaneous melanoma and orbital involvement. The patients' metastatic disease responded well to drug treatment. As of this writing, 2 patients have completed therapy and remain disease free at least 1 year after treatment completion; the other patient is still receiving treatment, and his orbital disease is responding. The authors herein describe the use of PD-1 inhibitors as a new alternative in the treatment of metastatic melanoma to the orbit or metastatic ocular adnexal melanomas in these clinical settings.

Sentinel lymph node biopsy for ocular adnexal melanoma.

BACKGROUND: We sought to update our prior report of findings on sentinel lymph node biopsy (SLNB) and predictors of a positive SLN in patients with conjunctival or eyelid melanoma. METHODS: We reviewed the records of all patients with ocular adnexal melanoma who underwent SLNB at one institution during 2000-2015. We determined rates of positive and false-negative findings on SLNB, primary tumour features correlated with positive findings and rate of nodal recurrence (false-negative event) after negative findings. RESULTS: The study included 51 patients, 31 with conjunctival and 20 with eyelid melanoma. These patients include 30 patients who underwent SLNB during 2000-2008, described in our previous report, and 21 additional patients who underwent SLNB during 2008-2015. There were 30 women and 21 men with median age at SLNB of 62 years (range, 24-83). The nodal basins most commonly sampled were intraparotid (27 patients) and level II (14 patients). Ten patients had positive SLNB findings. Compared to tumours with negative findings, tumours with positive findings had greater median thickness (3.5 mm versus 2.2 mm, p = 0.04), greater median number of mitotic figures (6 versus 2, p = 0.03) and greater incidence of ulceration (80% versus 26%, p = 0.003). Perineural and vascular invasion were not significantly associated with positive findings. There were three false-negative events. Three patients (6%) had temporary marginal mandibular weakness which resolved spontaneously. CONCLUSION: SLNB in patients with ocular adnexal melanoma is safe and identifies nodal micrometastasis in approximately 20% of cases. Histologic features associated with a positive SLN included greater tumour thickness, greater number of mitotic figures and ulceration.

Orotracheal Intubation Using the Retromolar Space: A Reliable Alternative Intubation Approach to Prevent Dental Injury.

Despite recent advances in airway management, perianesthetic dental injury remains one of the most common anesthesia-related adverse events and cause for malpractice litigation against anesthesia providers. Recommended precautions for prevention of dental damage may not always be effective because these techniques involve contact and pressure exerted on vulnerable teeth. We describe a novel approach using the retromolar space to insert a flexible fiberscope for tracheal tube placement as a reliable method to achieve atraumatic tracheal intubation. Written consent for publication has been obtained from the patient.