[BILATERAL OCULAR PLASMACYTOMA PRESENTING AS ACUTE ANTERIOR UVEITIS].

INTRODUCTION: A 64-year-old woman, presented to the ophthalmology outpatient clinic with abrupt onset of pain, blurred vision and redness in her right eye. Her medical history is remarkable for multiple myeloma, with successful bone marrow transplantation and recurrent disease as secondary plasma cell leukemia, managed with a biologic agent. Examination revealed severe fibrinous anterior uveitis, accompanied by keratic precipitates, rubeosis iridis and raised intra-ocular pressure (IOP) and normal fundus. The patient was treated intensively with topical steroids, IOP lowering agents, systemic acyclovir and prednisone. Response was partial, with further development of posterior synechiae, iris bombe and 360o angle closure. An anterior segment ultrasound demonstrated severely thickened iris. The appearance of bilateral sub-conjunctival salmon patches in both eyes facilitated histopathologic diagnosis by extraocular tissue biopsy which revealed plasma cells infiltration, suggestive of plasmacytoma. Ruthenium plaque radiotherapy administered in a 40Gy dose was initiated in both eyes with a new cycle of systemic chemotherapy. Complete regression after treatment was achieved bilaterally. AIMS: To report a case of bilateral ocular plasmacytoma presenting as an acute anterior uveitis. BACKGROUND: Plasmacytoma, associated with multiple myeloma, is a solid tumor of the lymphoid system composed of monoclonal plasma cells. Ocular involvement is rare and direct infiltration of both eyes is even rarer. METHODS: A case report. CONCLUSIONS: Extramedullary plasmacytoma rarely involves ocular structures. In the setting of systemic malignancy, ocular involvement should be considered, especially when acute inflammation is recalcitrant to therapy.

Telemedicine comes of age during coronavirus disease 2019 (COVID-19): An international survey of oculoplastic surgeons.

PURPOSE: The Coronavirus disease 2019 (COVID-19) pandemic is an ongoing healthcare crisis that continues its worldwide spread. Ophthalmologists are at high risk of acquiring and transmitting the virus. Telemedicine platforms have evolved and may play an important role in attenuating this risk. For patients, these platforms provide the possibility of clinic consultation without the concerns of a clinic visit. We aimed to assess the utilization of telemedicine by oculoplastics specialists worldwide during the COVID-19 pandemic. METHODS: A 13-item survey was distributed internationally to practicing oculoplastic surgeons. Collected data included demographics, clinical practice variables and perceptions regarding telemedicine. Significance of associations and single survey items was evaluated by Chi-squared and z-score of proportions tests, respectively. RESULTS: The questionnaire was completed by 70 oculoplastic surgeons (54.3% male, mean age 47.3 years, median experience 10 years) from eight countries, practicing in various clinical settings (50.0% hospitals, 45.7% private clinics, 4.3% community clinics). Most respondents reported telemedicine to be an effective tool for oculoplastic consultations (67.1%, p = 0.004), while only 12.8% (p < 0.00001) had incorporated this modality into clinical practice prior to the pandemic. Even though a vast majority (98.6%) of participants had limited outpatient activity, most (55.7%) felt unprotected from the virus. Telemedicine had been incorporated by 70.5% (p = 0.001) of respondents during the COVID-19 pandemic, whereas most (57.1%) predicted continued use of the modality. CONCLUSION: Telemedicine can be effectively and rapidly incorporated into the clinical practice of oculoplastic surgeons during the COVID-19 pandemic. Further research into the most effective utilization of these platforms appears warranted.

Efficacy of Vismodegib for the Treatment of Orbital and Advanced Periocular Basal Cell Carcinoma.

PURPOSE: To evaluate the effectiveness of vismodegib, a Hedgehog pathway inhibitor, in treating orbital and advanced periocular basal cell carcinoma (BCC) in Israeli multidisciplinary medical centers. DESIGN: Retrospective case series. METHODS: Background, treatment, and outcome data were retrospectively collected from the medical records of all patients with locally advanced and metastatic orbital or periocular BCC treated with vismodegib in 2012-2017 at 2 tertiary medical centers. RESULTS: The cohort included 21 patients (16 male) of median age 76 years with periocular (n=6) or orbital (n=15) BCC. Median duration of treatment was 9 months, with follow-up of 26 months (range 9-60 months) overall and 17 months after treatment cessation. Clinical response was complete in 10 patients, partial in 10 patients, and stable in 1 patient. Among the complete responders, 5 maintained a complete response at 16 months, and 3 who stopped treatment had a recurrence 8 months later. Almost all treatment-related adverse reactions were graded 1 or 2 (low-grade). The most common grade 1 or 2 complications were muscle spasm (76%), followed by dysgeusia (57%), alopecia (47%), weight loss (47%) and decreased appetite (19%). The only grade 3 or 4 adverse event was hepatotoxicity (10%). Eight patients discontinued treatment because of side effects. Five patients died, most from reasons unrelated to vismodegib therapy, except for 1 patient who died from possibly treatment-related sepsis (grade 5 adverse event). CONCLUSIONS: To our knowledge, this is the only study generated outside the United States and Europe, and it represents the largest study to date on vismodegib therapy for locally advanced periocular BCC. Treatment according to an individualized maximally tolerated dose may achieve a comparable response to the ERIVANCE protocol. Longer-term studies are needed to assess prognosis.

Analysis of Long-term Outcomes of Radiotherapy and Verteporfin Photodynamic Therapy for Circumscribed Choroidal Hemangioma.

PURPOSE: To determine the long-term therapeutic outcome for different treatments of circumscribed choroidal hemangioma (CCH). DESIGN: Retrospective observational study. SUBJECTS: Patients with newly diagnosed CCH. METHODS: Observation, verteporfin (Visudyne) photodynamic therapy (PDT), lens-sparing external beam radiotherapy (LS-EBRT), or plaque brachytherapy. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at baseline and throughout follow-up, tumor dimensions, and OCT central thickness (where available) at baseline and throughout follow-up were recorded. RESULTS: There were 60 treatment-naïve consecutive cases with CCH between January 2000 and June 2014; 42 (70%) received treatment. These were LS-EBRT (23/60 [38%]; mean follow-up, 45.5 months), PDT (16/60 [27%]; mean follow-up, 38 months), and plaque radiotherapy (3/60 [5%]; mean follow-up, 92 months). Macular location, mottled or orange pigment, and absence of drusen were significantly more frequent in the treatment group. In the LS-EBRT group, median thickness reduction on ultrasound B scan was 1.6 mm (mean ± standard deviation, 1.65±1.6; range, -6.5 to +0.7). The mean ± standard deviation BCVA gain was 0.22±0.34, with >3 Snellen lines in 48% of cases. Kaplan-Meier estimates were 80% for any gain and 40% for >3 Snellen lines gain at 5 years. In the PDT group, the median decrease in thickness was 0.95 mm (mean ± standard deviation, 1.0±0.8; range, -2.5 to +0.2). The mean ± standard deviation BCVA gain was at 0.3±0.51, with >3 Snellen lines in 30% of cases. Kaplan-Meier estimates were 93% for any gain and 68% for >3 Snellen lines at 5 years. Double versus single duration PDT had more favorable outcomes with a greater reduction in tumor thickness (P = 0.04), central retinal thickness (P = 0.02), and improvement in visual acuity (median, 0.33 vs -0.05). There was no difference in decrease in tumor thickness or BCVA gain between the LS-EBRT and PDT groups. With plaque brachytherapy, the mean decrease in thickness was 2.5 mm, but BCVA loss of >2 Snellen lines was noted in all 3 cases at the end of follow-up. Radiation complications developed in 10 of 23 cases (43.5%) from the LS-EBRT group and 2 of 3 cases (67%) from the plaque brachytherapy group. CONCLUSIONS: LS-EBRT is equivalent to PDT in CCH management for post-treatment BCVA and tumor thickness reduction. The risk of LS-EBRT and plaque brachytherapy was late radiation-related complications. Double duration PDT was more favorable than single duration.

Visual Loss from Choroidal Melanoma Mimicking Neurological Syndromes.

Melanoma of the eye is rare, but can mimic a range of disorders. This report highlights 2 cases of choroidal melanoma with vision loss mimicking neurological diagnoses. The first patient is a 41-year-old white male with a known history of multiple sclerosis and a previous episode of optic neuritis in the right eye, who presented with a 6-month history of decreased vision in the same eye, and occasional photopsiae. He was treated with 2 courses of oral steroids for presumed recurrent optic neuritis. After a temporary improvement in his symptoms, his vision worsened, following which he had a head MRI, which revealed a solid intraocular mass. He was subsequently diagnosed with a choroidal melanoma for which he was treated successfully with ruthenium-106 plaque brachytherapy. The second patient is a 57-year-old female, who presented with a progressive cerebellar syndrome under investigation by the neurology service, as well as decreased vision in the right eye. Her visual acuity gradually deteriorated and her neurological assessment, which included a PET-CT, revealed uptake in the right eye. The diagnosis of a choroidal melanoma was made, and following conservative treatment with proton beam radiotherapy, she had an enucleation of the eye. Intraocular tumours can masquerade as many different entities. Unexplained unilateral visual loss, especially if it is atypical for a neurological syndrome, should prompt dilated fundoscopy and referral to an ophthalmologist.

Third-generation ELISA thyrotropin-receptor antibody levels as an adjuvant tool to guide management of patients with Graves orbitopathy.

OBJECTIVE: When assessing patients with Graves orbitopathy (GO) in an endocrinology outpatient setting, it is desirable to have a diagnostic laboratory tool to complement the clinical activity score (CAS) in distinguishing patients with moderate-severe active GO requiring high-priority ophthalmological care from those with mild or inactive GO who can be electively scheduled and to asses response to treatment. METHODS: A retrospective study was conducted to evaluate the correlation between thyrotropin-receptor antibody (TRAb)-Fast-enzyme-linked immunosorbent assay (ELISA) results and CAS in patients with GO seen at a tertiary referral center between 2000 and 2009. TRAb levels were quantified using a commercial third-generation TRAb-specific ELISA. Other variables analyzed included smoking status, gender, age, and thyroid-stimulating hormone level. RESULTS: Fifty-five patients with GO had a documented CAS within a mean of 22 days from the recorded TRAb level determined by TRAb-Fast-ELISA. An increase in TRAb-Fast-ELISA of 1 unit was associated with a 15% (95% confidence interval, 7-24%) increase in the odds ratio of elevated CAS. A TRAb-Fast-ELISA result ≥10 as a diagnostic tool to predict a CAS ≥3 was assessed and was found to have a specificity of 86.7% and a sensitivity of 87.2% for moderately severe GO. CONCLUSION: Our results demonstrate the ability to predict a patient's GO activity level by antibody titer. A TRAb-Fast-ELISA result ≥10 can be used as a complementary diagnostic tool to predict a CAS ≥3.

Gucy2f zebrafish knockdown--a model for Gucy2d-related leber congenital amaurosis.

Mutations in retinal-specific guanylate cyclase (Gucy2d) are associated with Leber congenital amaurosis-1 (LCA1). Zebrafish offer unique advantages relative to rodents, including their excellent color vision, precocious retinal development, robust visual testing strategies, low cost, relatively easy transgenesis and shortened experimental times. In this study we will demonstrate the feasibility of using gene-targeting in the zebrafish as a model for the photoreceptor-specific GUCY2D-related LCA1, by reporting the visual phenotype and retinal histology resulting from Gucy2f knockdown. Gucy2f zebrafish LCA-orthologous cDNA was identified and isolated by PCR amplification. Its expression pattern was determined by whole-mount in-situ hybridization and its function was studied by gene knockdown using two different morpholino-modified oligos (MO), one that blocks translation of Gucy2f and one that blocks splicing of Gucy2f. Visual function was assessed with an optomotor assay on 6-days-post-fertilization larvae, and by analyzing changes in retinal histology. Gucy2f knockdown resulted in significantly lower vision as measured by the optomotor response compared with uninjected and control MO-injected zebrafish larvae. Histological changes in the Gucy2f-knockdown larvae included loss and shortening of cone and rod outer segments. A zebrafish model of Gucy2f-related LCA1 displays early visual dysfunction and photoreceptor layer dystrophy. This study serves as proof of concept for the use of zebrafish as a simple, inexpensive model with excellent vision on which further study of LCA-related genes is possible.

Visual outcome in meningiomas around anterior visual pathways treated with linear accelerator fractionated stereotactic radiotherapy.

PURPOSE: Meningiomas threatening the anterior visual pathways (AVPs) and not amenable for surgery are currently treated with multisession stereotactic radiotherapy. Stereotactic radiotherapy is available with a number of devices. The most ubiquitous include the gamma knife, CyberKnife, tomotherapy, and isocentric linear accelerator systems. The purpose of our study was to describe a case series of AVP meningiomas treated with linear accelerator fractionated stereotactic radiotherapy (FSRT) using the multiple, noncoplanar, dynamic conformal rotation paradigm and to compare the success and complication rates with those reported for other techniques. PATIENTS AND METHODS: We included all patients with AVP meningiomas followed up at our neuro-ophthalmology unit for a minimum of 12 months after FSRT. We compared the details of the neuro-ophthalmologic examinations and tumor size before and after FSRT and at the end of follow-up. RESULTS: Of 87 patients with AVP meningiomas, 17 had been referred for FSRT. Of the 17 patients, 16 completed >12 months of follow-up (mean 39). Of the 16 patients, 11 had undergone surgery before FSRT and 5 had undergone FSRT as first-line management. Tumor control was achieved in 14 of the 16 patients, with three meningiomas shrinking in size after RT. Two meningiomas progressed, one in an area that was outside the radiation field. The visual function had improved in 6 or stabilized in 8 of the 16 patients (88%) and worsened in 2 (12%). CONCLUSIONS: Linear accelerator fractionated RT using the multiple noncoplanar dynamic rotation conformal paradigm can be offered to patients with meningiomas that threaten the anterior visual pathways as an adjunct to surgery or as first-line treatment, with results comparable to those reported for other stereotactic RT techniques.

Bevacizumab for choroidal neovascularization related to inflammatory diseases.

PURPOSE: The purpose of this study was to report our experience with intravitreal bevacizumab for inflammation-related choroidal neovascularization in two tertiary centers. METHODS: This study was a retrospective analysis of patients with choroidal neovascularization related to inflammatory diseases, treated with intravitreal bevacizumab injections (1.25 mg/0.05 mL). RESULTS: Ten eyes of 10 patients (range, 14-78 years; mean age, 44 years) with underlying uveitis were treated with intravitreal bevacizumab for inflammation-related choroidal neovascularization from 2006 to 2008. Mean follow-up time was 13 +/- 8 months, and the mean number of injections was 2.7 +/- 2. Resolved leakage on fluorescein angiography and resolution of subretinal fluid on optical coherence tomography occurred in all patients, with improvement in visual acuity in 9 of 10 eyes and no change in visual acuity in 1 of 10 eyes. Seven patients received additional treatment based on the underlying condition. Mean macular thickness on optical coherence tomography decreased from 394 +/- 116 microm to 254 +/- 52 microm (P < 0.01). Mean visual acuity improved from 0.87 +/- 0.74 logarithm of the minimum angle of resolution to 0.38 +/- 0.63 (P = 0.005). Seven patients reached a visual acuity of 0.2 logarithm of the minimum angle of resolution (Snellen 6/9) or better. CONCLUSION: Intravitreal bevacizumab is an effective treatment for choroidal neovascularization related to inflammatory diseases when inflammation is controlled.