Taste buds consist of specialized epithelial cells which detect particular tastants and synapse onto the afferent taste nerve innervating the endorgan. The nature of the neurotransmitter released by ...taste cells onto the nerve fiber was enigmatic early in this century although neurotransmitters for other sensory receptor cell types, e.g. hair cells, photoreceptors, was known for at least a decade. A 1999 paper by Burnstock and co-workers (Bo et al., 1999) showing the presence of P2X receptors on the afferent nerves served as a springboard for research that ultimately led to the discovery of ATP as the crucial neurotransmitter in the taste system (Finger et al., 2005). Subsequent work showed that a subpopulation of taste cells utilize a unique release channel, CALHM1/3, to release ATP in a voltage-dependent manner. Despite these advances, several aspects of purinergic transmission in this system remain to be elucidated.
Abstract Radiation therapy is widely used for the treatment of orbital tumors and inflammatory disease. Both external beam teletherapy and implant brachytherapy radiation techniques are employed. ...External beam radiation therapy is the most common. It involves directing an external radiation source towards the eye, sinuses, and orbit. Whereas most patients are treated with linear accelerator–derived external beam radiation therapy, proton, neutron stereotactic radiosurgery, gamma knife, and intensity-modulated radiation therapy have become more available in developed countries. Radiation can be used alone or together with surgery or chemotherapy. Implant radiation therapy (brachytherapy) is also used to treat orbital tumors. Brachytherapy involves surgical placement of radiation sources within the tumor or targeted volume. Characteristically conformal, brachytherapy increases the dose within the target while maximally decreasing exposure of normal tissues. Orbital brachytherapy can be used to boost the dose to the target volume prior to orbital external beam radiation therapy. Herein, I explore the unique challenges associated with irradiation of the orbit, basic radiobiology, doses, indications, and results of treatment. The tolerances of normal ocular and orbital tissues are reported. This review of the literature offers a unique perspective, synthesizing the world's experience on the use of orbital radiation therapy.
Purpose: To reveal early intervention outcomes for patients describing with choroidal metastasis. Methods: A retrospective interventional case series on 27 eyes of 22 patients treated for choroidal ...metastasis with external beam radiation therapy (EBRT) With and without intravitreal injections. The prescribed radiation dose was a mean and median 30 Gy (range of 30-40 Gy in 180-200 cGy daily fractions). Outcome measures included change in tumor thickness, subretinal fluid, visual acuity, radiation oculopathy, and survival. Results: Decreased vision was the most common presenting symptom (n = 20/27, 74%). Pre-treatment vision for subfoveal lesions was a mean 20/400, median 20/200, and range 20/40 to hand motions (HM). Pre-treatment vision for extrafoveal tumors were a mean 20/40, median 20/25, range 20/20 to counting fingers (CF) which improved to a mean 20/32, median 20/20, range 20/12.5 to 20/200. Local control, with ultrasonographic height regression (44.5%; mean: 2.7-1.5 mm), was observed in all eyes at mean follow-up of 16 months (range: 1-72 months). Intravitreal anti-vascular endothelial growth factor (anti-VEGF) was given in nine cases (n = 9/27, 33%) to slow the growth of the metastasis and suppress their exudative detachments and to treat radiation maculopathy in 10 cases (n = 10/27, 37%). Late radiation complications included keratoconjunctivitis sicca in four cases (n = 4/27, 15%), exposure keratopathy in two cases (n = 2/27, 7%), and radiation retinopathy in 10 cases (n = 10/27, 37%). Of the 23 phakic eyes, four (n = 4, 17%) developed cataract. Conclusion: Radiation therapy with or without intravitreal anti-VEGF injections was a safe and effective treatment for choroidal metastasis. It was associated with local tumor control, reduction of secondary retinal detachments, and vision preservation.
Radiation therapy has saved both sight and life for eye cancer patients. The most common methods include ophthalmic plaque brachytherapy and external beam techniques. However, subsequent ...dose-dependent radiation vasculopathy invariably occurs within and around the targeted zone. In 2006, Finger discovered that periodic intravitreal anti-vascular endothelial growth factor (anti-VEGF) bevacizumab could reverse and suppress intraocular radiation vasculopathy. At first, it was administered at the onset of radiation-related vision loss. Though bevacizumab induced regression of macular oedema, retinal haemorrhages and cotton-wool infarcts, most patients were left with residual retinal damage, manifest as metamorphopsia and loss of vision. These results led to earlier and earlier anti-VEGF interventions: first after signs of progressive radiation retinopathy, and then for signs of radiation maculopathy, and finally for high-risk eyes with no clinical signs of retinopathy. Earlier initiation of intravitreal anti-VEGF therapy typically resulted in greater restoration and preservation of macular anatomy, reductions of retinal haemorrhages, resolution of cotton-wool spots and vision preservation. Recent research on optical coherence tomography angiography (OCT-A) has revealed that radiation vasculopathy occurs prior to clinical ophthalmic signs or symptoms. Therefore, it seemed reasonable to consider treating high-risk patients (considered certain to eventually develop radiation maculopathy) to prevent or delay vision loss. Herein, we describe the evolution of treatment for radiation maculopathy as well as recent research supporting anti-VEGF treatment of high-risk patients immediately following radiation to maximize vision outcomes.
To report on bevacizumab treatment for radiation retinopathy affecting the macula.
Twenty-one patients with radiation retinopathy (edema, hemorrhages, capillary dropout, and neovascularization) and a ...subjective or objective loss of vision were treated. Treatment involved intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) every 6-12 weeks. Treatment was discontinued at patient request or if there was no measurable response to therapy. Main outcome measures included best corrected visual acuity, ophthalmic examination, retinal photography, and angiography.
Bevacizumab treatment was followed by reductions in retinal hemorrhage, exudation, and edema. Visual acuities were stable or improved in 86% (n=18). Three patients discontinued therapy. Each was legally blind before treatment (n=1), experienced little to no subjective improvement (n=2), or was poorly compliant (n=2). Three patients (14%) regained 2 or more lines of visual acuity. No ocular or systemic bevacizumab-related side effects were observed.
Intravitreal bevacizumab can be used to treat radiation retinopathy. In most cases treatment was associated with decreased vascular leakage, stabilization, or improved vision. An anti-vascular endothelial growth factor strategy may reduce tissue damage associated with radiation vasculopathy and neuropathy.
Purpose
To report long-term experience with intravitreal anti–vascular endothelial growth factor treatment for radiation maculopathy.
Methods
From 2005-2015, 120 consecutive patients underwent ...intravitreal anti-VEGF therapy for radiation maculopathy. Inclusion criteria included a diagnosis of uveal melanoma treated with plaque radiotherapy and subsequent macular radiation vasculopathy (exudate, retinal hemorrhage, intraretinal microangiopathy, neovascularization, edema). Anti-VEGF therapy involved continuous injections in 4- to 12-week intervals with doses of 1.25 mg/0.05 mL, 2.0 mg/0.08 mL, 2.5 mg/0.1 mL, or 3.0 mg/0.12 mL of bevacizumab as well as 0.5 mg/0.05 mL or 2.0 mg/0.05 mL of ranibizumab. Goals were maintenance of visual acuity and normative macular anatomy. Safety and tolerability (retinal detachment, hemorrhage, infection), visual acuity, central foveal thickness on optical coherence tomography imaging, and clinical features of radiation maculopathy were analyzed.
Results
Progressive reductions in macular edema, hemorrhages, exudates, cotton-wool spots, and microangiopathy were noted. At last follow-up, 80% remained within 2 lines of their initial visual acuity or better, with a mean treatment interval of 38 months (range 6-108 months). Kaplan-Meier analysis of the probability of remaining within 2 lines of initial visual acuity was 69% at 5 years and 38% at 8 years of anti-VEGF therapy. Discontinuation of therapy was rare. Relatively few acute or long-term side effects were noted, allowing for good long-term patient accrual.
Conclusions
Continuous intravitreal anti-VEGF therapy in patients with radiation maculopathy was well-tolerated and preserved vision. In most cases, reductions or resolution of retinal hemorrhages, cotton-wool spots, and retinal edema were noted for up to 10 years.
Herein, we describe the use of systemic immunotherapy for both locally advanced and metastatic conjunctival melanoma. Current treatments for advanced conjunctival melanoma typically result in poor ...local control leading to disfiguring orbital exenteration surgery. Locoregional spread of conjunctival malignant melanoma typically requires pre-auricular and cervical lymph node dissection with post-operative adjuvant radiation therapy. In addition, classic systemic chemotherapy has been unsuccessful in the treatment of metastatic disease.
This is a retrospectively analyzed clinical case series of 5 patients with biopsy proven conjunctival melanoma who were treated with checkpoint inhibition therapy. Of these, 3 patients were treated for residual ocular disease present after failing multiple local therapies and refusing orbital exenteration surgery and two (with local ocular control) for metastatic conjunctival melanoma. Both those with locally advanced disease and patients with metastatic disease received an anti-PD1 agent in combination with another immunotherapeutic agent. All 5 were given multiple cycles of systemic anti-PD1 therapy, 1 was initially treated with single agent ipilimumab (3 mg/kg) prior to approval of anti-PD1 agents and two received interferon eye drops. As part of each ophthalmic examination, photographs of all conjunctival and eyelid surfaces were obtained. Systemic evaluations involved initial staging scans as well as periodic re-imaging.
All cases have shown responses. Of the 2 complete responses, 1 was a patient with systemic disease. No patients developed ocular toxicity or loss of vision. However, systemic adverse effects included adrenal insufficiency, Grade-III colitis, Grade-II dermatitis, Grade-II hepatotoxicity and Grade-II pneumonitis.
This report suggests that systemic immunotherapy with or without topical interferon is effective in treatment of malignant melanoma of the conjunctiva. Therefore, it can be considered for patients with advanced local conjunctival melanoma, those who refuse orbital exenteration surgery and those with systemic metastasis.
To describe a pilot study on the use of single-session, high-dose-rate, Food and Drug Administration–cleared, yttrium-90 (Y90) plaque brachytherapy for iris and iridociliary melanoma.
A ...single-center, clinical case series.
Six consecutive patients were included in this study. Each was diagnosed with an iris or iridociliary melanoma based on clinical examination with or without biopsy.
Each tumor was staged according to the American Joint Committee on Cancer criteria and received Y90 eye plaque brachytherapy. The main variables were tumor size, patient age, sex, and method of diagnosis (clinical or biopsy). Surgical techniques, treatment durations, and ocular side effects were recorded. Local control was defined as a lack of tumor growth or regression determined by clinical examinations, including slit-lamp and gonio photography, as well as high-frequency ultrasound measurements. Toxicity parameters included acute and short-term corneal/scleral change, anterior segment inflammation, and cataract progression.
Local and systemic cancer control, tumor regression, visual acuity, as well as radiation-related normal tissue toxicity.
High-dose-rate Y90 plaque brachytherapy was used to treat small (American Joint Committee on Cancer cT1) category melanomas. Single-surgery high-dose-rate irradiations were performed under anesthesia. Because of short treatment durations, high-dose-rate Y90 did not require the additional procedures used for low-dose-rate plaque (e.g., sutures, amniotic membrane epicorneal buffering, Gunderson flaps, and second surgeries for plaque removal). Only conjunctival recession was used to avoid normal tissue irradiation. High-dose-rate Y90 treatment durations averaged 8.8 minutes (median, 7.9; range, 5.8–12.9). High-dose-rate Y90 brachytherapy was associated with no periorbital, corneal (Descemet folds), or conjunctival edema. There was no acute or short-term anterior uveitis, secondary cataract, scleropathy, radiation retinopathy, maculopathy, or optic neuropathy. The follow-up was a mean of 16.0 (range 12–24) months. Evidence of local control included a lack of expansion of tumor borders (n = 6, 100%), darkening with or without atrophy of the tumor surface (n = 5/6, 83%), and a mean 24.5% reduction in ultrasonographically measured tumor thickness. There were no cases of metastatic disease.
High-dose-rate Y90 brachytherapy allowed for single-surgery, minimally invasive, outpatient irradiation of iris and iridociliary melanomas.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
To investigate and characterize the clinical features of subtype-specific orbital lymphoma.
Retrospective, interventional case series.
The study included 7 international eye cancer centers. Patient ...data were collected from January 1, 1980 through December 31, 2017. A total of 797 patients with a histologically verified orbital lymphoma were included. The primary endpoints were overall survival, disease-specific survival, and progression-free survival.
The median age was 64 years, and 51% of patients (n = 407) were male. The majority of lymphomas were of B-cell origin (98%, n = 779). Extranodal marginal zone B-cell lymphoma (EMZL) was the most frequent subtype (57%, n = 452), followed by diffuse large B-cell lymphoma (DLBCL) (15%, n = 118), follicular lymphoma (FL) (11%, n = 91), and mantle cell lymphoma (MCL) (8%, n = 66). Localized Ann Arbor stage IE EMZL and FL were frequently treated with external beam radiation therapy. DLBCL, MCL, and disseminated EMZL and FL were primarily treated with chemotherapy. EMZL and FL patients had a markedly better prognosis (10-year disease-specific survival of 92% and 71%, respectively) than DLBCL and MCL patients (10-year disease-specific survival of 41% and 32%, respectively).
Four lymphoma subtypes were primarily found in patients with orbital lymphoma: EMZL, DLBCL, FL, and MCL. The histologic subtype was found to be the main predictor for outcome, with EMZL and FL patients having a markedly better prognosis than DLBCL and MCL.
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