onjunctival melanoma is a rare tumor with the potential to invade the eye, eyelid, and orbit and spread to regional lymphatics and distant sites, including the lungs, skin, liver, and brain. It was previously reported to have local recurrence rates of 36% to 45% at 5 years and 31% to 59% at 10 years. 1 Lymph node involvement was found in 19% of patients with conjunctival melanoma and systemic metastases were found in 19% of patients within 10 years after initial diagnosis. 1,2 Melanoma-related death was reported in 9% to 18% of patients at 5 years. [1][2][3] The mainstay of treatment for local control is surgical excision with margins clear of tumor; locally advanced disease may necessitate an orbital exenteration. Adjuvant treatments include topical chemotherapy and radiotherapy and are aimed at improving local control. Historically, treatment options for metastatic conjunctival melanoma have been limited.In recent years, immune checkpoint inhibitors, a new class of drugs, have been successfully used to treat metastatic cutaneous melanoma. Immune checkpoint inhibitors prevent cancer cells from activating mechanisms that enable the cells to evade the host's immune system. Immune checkpoint inhibitors, by blocking receptors on the surface of activated T lymphocytes, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), facilitate the recognition of cancer cells by lymphocytes and a consequent effective immune response. Ipilimumab (a CTLA-4 inhibitor), pembrolizumab (a PD-1 inhibitor), and nivolumab (a PD-1 inhibitor) are approved by the US Food and Drug Administration for the 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 PARTICIPANTSA 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 MEASURESResponse to treatment and disease-free survival. RESULTSOf 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 ...

Purpose To determine rates of globe-sparing treatment and useful final visual function in patients with primary lacrimal sac/nasolacrimal duct carcinomas treated with multidisciplinary therapy. Methods The medical records of 14 patients with primary lacrimal sac/nasolacrimal duct carcinoma treated at 1 institution were retrospectively reviewed. Results The patients were 9 men and 5 women; the median age at diagnosis was 58.5 years (range, 45–73 years). Seven patients presented with epiphora, 7 with a palpable mass in the inferomedial orbit, and 2 with dacryocystitis. In 3 patients, the diagnosis of cancer was not considered until during or after dacryocystorhinostomy (DCR). Seven patients had squamous cell carcinoma, 2 transitional cell carcinoma, 2 adenoid cystic carcinoma, and 1 each adenocarcinoma, poorly differentiated carcinoma, and inverted papilloma with carcinoma in situ transformation. Nine patients underwent surgical resection of the lacrimal sac and nasolacrimal duct, resection of the medial upper and lower eyelids including canaliculi, partial ethmoidectomy, and medial maxillectomy. One patient underwent lacrimal sac biopsy only as another primary malignancy was discovered on the work-up for systemic disease. Four patients underwent orbital exenteration because of extensive involvement of the orbital soft tissue. Radiotherapy was recommended for 13 patients; in 1 patient, radiotherapy was not recommended because the patient had an inverted papilloma with carcinoma in situ transformation that was completely excised. The median radiation dose was 60 Gy. Eight patients received chemotherapy concurrent with radiation therapy (5 patients), as neoadjuvant treatment (1 patient), or for progressive or metastatic disease (3 patients). The median follow-up time was 27 months (range, 6–96 months). In 10 patients, the globe was spared. In 9 of these 10 patients, visual acuity was the same as at baseline or better than 20/40 at last follow-up. Conclusions With multidisciplinary therapy, the eye can be spared and reasonable visual function can be preserved in most patients with primary lacrimal sac/nasolacrimal duct carcinomas.

The clinical features of diffuse large B-cell lymphoma (DLBCL) subtype of ocular adnexal lymphoma have not previously been evaluated in a large cohort to our knowledge. OBJECTIVE To investigate the clinical features of ocular adnexal DLBCL (OA-DLBCL). DESIGN, SETTING, AND PARTICIPANTS This retrospective international cooperative study involved 6 eye cancer centers. During 30 years, 106 patients with OA-DLBCL were identified, and 6 were excluded from the study. The median follow-up period was 52 months. MAIN OUTCOMES AND MEASURES Overall survival, disease-specific survival (DSS), and progression-free survival were the primary end points. RESULTS One hundred patients with OA-DLBCL were included in the study (median age, 70 years), of whom 54 (54.0%) were female. The following 3 groups of patients with lymphoma could be identified: primary OA-DLBCL (57.0%), OA-DLBCL and concurrent systemic lymphoma (29.0%), and ocular adnexal lymphoma relapse of previous systemic lymphoma (14.0%). Of 57 patients with primary OA-DLBCL, 53 (93.0%) had Ann Arbor stage IE disease, and 4 (7.0%) had Ann Arbor stage IIE disease. According to the TNM staging system, 43 of 57 (75.4%) had T2 tumors. Among all patients, the most frequent treatments were external beam radiation therapy with or without surgery (31.0%) and rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine sulfate, prednisone (CHOP) or rituximab-CHOP-like chemotherapy with or without external beam radiation therapy (21.0%). The 5-year overall survival among the entire cohort was 36.0% (median, 3.5 years; 95% CI, 2.5-4.5 years). Relapse occurred in 43.9% (25 of 57) of patients with primary OA-DLBCL. Increasing T category of the TNM staging system was predictive of DSS (P = .04) in primary OA-DLBCL, whereas the Ann Arbor staging system was not. However, when taking all 100 patients into account, Ann Arbor stage was able to predict DSS (P = .01). Women had a longer median DSS than men (9.8 years; 95% CI, 1.9-17.7 years vs 3.3 years; 95% CI, 1.6-5.0; P = .03). CONCLUSIONS AND RELEVANCE Most patients with primary OA-DLBCL were seen with Ann Arbor stage IE and TNM T2 disease. The 5-year overall survival was between 2.5 and 4.5 years, which is the 95% CI around the median of 3.5 years in this cohort. Increasing T category appears to be associated with decreased DSS among patients with primary OA-DLBCL. When taking all patients into account, sex and Ann Arbor stage also seem to be DSS predictors.

Anti-vascular endothelial growth factor agents are frequently used to treat a variety of ocular neovascular diseases. While agents like bevacizumab and ranibizumab appear to be safe and effective, there have been reports of severe intraocular inflammation as well as sustained elevation of intraocular pressure (IOP) after single or multiple intravitreal injections of these protein-based therapeutics. The true mechanism leading to inflammation and/or sustained spikes in IOP remains unknown. We report a patient with sustained IOP elevation and kerato-precipitates on the trabecular meshwork after multiple injections of both bevacizumab and ranibizumab. We propose that monomer antibodies, aggregated proteins, or other high molecular weight molecules might lead to inflammation in the trabecular meshwork and subsequent elevation in IOP.

The lack of increased thickness in 3-month-old diabetic rats in vivo raises the possibility that intracellular swelling is unlikely to underlie subnormal DeltaPo2 in experimental diabetes. In diabetic rats, the spatial disconnect between subnormal DeltaPo2 pansuperiorly and retinal thinning only superiorly to the optic nerve suggests that neurovascular coupling is perturbed.