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1.
Orbit ; 43(1): 49-57, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37052129

RESUMO

INTRODUCTION: Conjunctival melanoma (CM) has genetic characteristics that are similar to primary cutaneous melanoma (PCM). The management of advanced CM with orbital metastasis was limited until the adoption of novel immunotherapy agents that significantly improved the survival of metastatic PCM. PURPOSE: To review and compare the immune checkpoint inhibitor (ICI) treatment response in cases reported in the English literature with orbital involvement secondary to CM versus PCM. In addition, we report a case of local recurrence of CM in a young female after successful treatment with ICI. METHODS: In addition to reviewing the chart of one patient who presented to our clinic, we conducted a comprehensive literature review to identify CM cases and cases with orbital metastasis secondary to advanced CM and PCM. Outcomes included patient demographics, response to ICI, and associated adverse effects. RESULTS: There were ten cases with orbital involvement, four were secondary to CM, and six were metastasis from PCM. Orbital metastasis from PCM regressed following treatment with ICI agents, whereas those secondary to CM resolved completely. There were 19 cases of CM without orbital invasion. Of the 29 cases identified, complete resolution of ocular melanoma was achieved in 15 patients, representing 52% of the cases collectively, and none of them reported recurrence except in our case. CONCLUSION: CM with orbital invasion responds well to ICIs, with manageable toxic effects. Despite the complete resolution, close observation is needed as the recurrence risk remains.


Assuntos
Neoplasias da Túnica Conjuntiva , Melanoma , Neoplasias Cutâneas , Humanos , Feminino , Melanoma/tratamento farmacológico , Melanoma/patologia , Neoplasias Cutâneas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Estudos Retrospectivos
2.
Clin Dermatol ; 42(1): 71-77, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37866412

RESUMO

Periocular and ocular surface nonmelanoma malignancies, including basal cell carcinoma (BCC), squamous cell carcinomas (SCC), and ocular surface squamous neoplasia (OSSN), are rare, but their management requires special considerations. The most common periocular malignancy is BCC, which constitutes 80% to 96% of tumors, followed by SCC, which represents 5% to 10% of tumors. OSSN represents a spectrum of diseases that encompass dysplastic alteration to the squamous epithelium of the eye. OSSN ranges from squamous dysplasia to conjunctival intraepithelial neoplasia/carcinoma in situ to invasive SCC, which is the most common ocular malignancy. These tumors can be staged using the eighth edition of the American Joint Committee on Cancer categorization system. The standard of care for periocular malignancies is Mohs micrographic surgery, while medical management with 5-fluorouracil (5-FU), interferon alfa-2b (INF), and mitomycin C (MMC) or "no touch" surgical excision are options for OSSN. Systemic therapies, including sonic hedgehog inhibitors for BCC and epidermal growth factor inhibitors and immune-checkpoint inhibitors for SCC, can be utilized for advanced disease. Recurrence rates are higher for periorbital and ocular malignancies than their respective cutaneous counterparts. These carcinomas and their respective treatments have unique side effects and considerations in an effort to preserve visual function.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Neoplasias Oculares , Neoplasias Cutâneas , Humanos , Proteínas Hedgehog , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Mitomicina/uso terapêutico , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/patologia , Neoplasias Cutâneas/tratamento farmacológico , Fluoruracila/uso terapêutico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia
3.
Eye (Lond) ; 38(1): 82-88, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37353510

RESUMO

OBJECTIVES: To investigate the long-term outcomes of oral doxycycline as first-line treatment in patients with conjunctival extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). METHODS: In this case series, the medical records of 67 patients with conjunctival MALT lymphoma who received doxycycline as their primary treatment and were followed up for at least 5 years were retrospectively reviewed. Progression-free survival (PFS) was analysed at 3, 5, and 10 years after the initial doxycycline treatment. A Cox proportional hazards model was used to assess the independent risk factors for progression. RESULTS: After the initial treatment, 25 patients (37.3%) achieved a complete response, 8 patients (11.9%) achieved a partial response, 30 patients (44.8%) showed stable disease, and 4 patients (6.0%) showed disease progression. The median PFS in all patients was 168 months, and the 3-, 5- and 10-year PFS rates for all patients were 70%, 65%, and 62%, respectively. No further progression was observed 6 years after the initial doxycycline treatment. Younger age and TNM stage T1c were significant risk factors for the time to progression in the multivariate Cox regression analysis (p < 0.05). Additional doxycycline (>2 cycles) showed no benefit. There were no serious adverse events associated with doxycycline therapy, and most patients were successfully salvaged by second-line treatments, including radiotherapy and chemotherapy. CONCLUSION: In this case series, oral doxycycline treatment yielded acceptable long-term PFS with minimal complications. Especially in patients with stage T1a or T1b conjunctival MALT lymphoma, first-line doxycycline treatment could be considered under close monitoring for at least 6 years.


Assuntos
Neoplasias da Túnica Conjuntiva , Linfoma de Zona Marginal Tipo Células B , Neoplasias Cutâneas , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/patologia , Doxiciclina/uso terapêutico , Estudos Retrospectivos , Estudos de Viabilidade , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento
4.
BMC Ophthalmol ; 23(1): 335, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37501105

RESUMO

PURPOSE: Ocular surface squamous neoplasia (OSSN) comprises a wide spectrum of squamous tumors, from which corneal/conjunctival intraepithelial neoplasia (CIN) is the most common one. The classic treatment is complete excision, but recurrence rates are high. Antineoplastic drugs such as mitomycin C (MMC) and interferon alpha 2b (IFNα2b) have been used as adjuvants or as primary treatment. To evaluate the efficacy and safety of topical IFNα2b and MMC in patients with CIN, a phase IIb double-blind clinical trial was performed. METHODS: Patients diagnosed with localized CIN were evaluated by slit lamp and impression cytology and were randomly given MMC 0.04% or INF2b (1 million IU/mL) 4 times daily until neoplasia resolution. Time of resolution and frequency of adverse effects were analyzed to determine the pharmacological efficacy and safety of both medications. RESULTS: Seventeen patients were included. Nine patients were treated with MMC and 8 with IFNα2b. All patients responded to treatment. The resolution time in days was 59.11 ± 24.02 in patients treated with MMC and 143.50 ± 47.181 in those treated with IFNα2b (p < 0.001). In the MMC group, one recurrence was reported (11%). There were no recurrences at 2 years of follow-up in the IFNα2b group. Regarding adverse effects, one or more mild adverse reaction occurred in 77% of patients managed with MMC and in 50% of patients managed with IFNα2b (p > 0.05). No serious adverse effects were reported. CONCLUSIONS: Topical chemotherapy with MMC and IFNα2b demonstrate pharmacological safety and efficacy. Therefore, these drugs could be considered as primary therapies for localized CIN .


Assuntos
Antineoplásicos , Carcinoma in Situ , Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Doenças da Córnea , Neoplasias Oculares , Humanos , Administração Tópica , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Doenças da Córnea/patologia , Neoplasias Oculares/induzido quimicamente , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Interferon-alfa/efeitos adversos , Mitomicina , Resultado do Tratamento
5.
Invest Ophthalmol Vis Sci ; 64(7): 29, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37335568

RESUMO

To summarize an invited lecture topic from the proceedings of the International Society of Ocular Oncology meeting in Leiden in 2022. Mechanism of action, indications, and the authors' clinical experience with immune checkpoint inhibitors in patients with locally advanced ocular adnexal squamous cell carcinoma are summarized. Several cases of locally advanced conjunctival, eyelid, and lacrimal sac/duct squamous cell carcinoma that were successfully treated with immune checkpoint inhibitors (PD-1 directed) are shared. Immune checkpoint inhibitors are effective at reducing tumor size and enabling eye-preserving surgery in patients with locally advanced ocular adnexal squamous cell carcinoma with orbital invasion. They present a new strategy for the treatment of locally advanced squamous cell carcinoma of the ocular adnexa and orbit.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Neoplasias Orbitárias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Órbita/patologia
6.
Klin Monbl Augenheilkd ; 240(7): 891-896, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36746398

RESUMO

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. METHODS: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. CONCLUSION: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Humanos , Mitomicina/uso terapêutico , Qualidade de Vida , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Interferon-alfa/uso terapêutico , Interferon-alfa/efeitos adversos , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Inquéritos e Questionários , Soluções Oftálmicas , Proteínas Recombinantes/uso terapêutico
7.
Eye (Lond) ; 37(5): 885-893, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36754986

RESUMO

Ocular surface squamous neoplasia (OSSN) is the most common non-melanocytic tumour of the ocular surface. Surgical excision with wide margins using the "no-touch" method was originally the most popular treatment for OSSN. However, in the past two decades, the use of topical medications for OSSN treatment has gained a reputation amongst ophthalmologists for being an effective alternative to surgical excision. Furthermore, technological advancements, such as those seen in high-resolution optical coherence tomography (HR-OCT) for the anterior segment, have facilitated the diagnosis and monitoring of OSSN. When selecting a topical agent, interferon alpha-2b (IFNα-2b) and 5-fluorouracil (5-FU) are two of the gentlest medications used for OSSN and are often considered first line therapies due to their high-resolution rates and mild side effect profiles. Mitomycin C (MMC), on the other hand, has a highly toxic profile; therefore, while effective, in our hands it is considered as a second-line treatment for OSSN if the other modalities fail. In addition, newer and less studied agents, such as immune checkpoint inhibitors, retinoic acid, aloe vera, and anti-vascular endothelial growth factor have anti-neoplastic properties and have shown potential for the treatment of OSSN. We enclose an updated literature review of medical treatments for OSSN.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Neoplasias Oculares , Humanos , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Fluoruracila/uso terapêutico , Mitomicina/uso terapêutico , Interferon alfa-2/uso terapêutico , Neoplasias Oculares/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos
8.
Cornea ; 42(5): 648-650, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36747320

RESUMO

PURPOSE: To report a case of fibrinous acute anterior uveitis associated with topical interferon-α2b (IFN-α2b) treatment for ocular surface squamous neoplasia in a patient with HLA-B27 uveitis predisposition. METHODS: Case report. RESULTS: We present the case of a 57-year-old man who received topical IFN-α2b as adjuvant therapy for a previously surgically removed ocular surface squamous neoplasia with affected surgical margins. Two weeks after topical IFN-α2b initiation, the patient was diagnosed with fibrinous acute anterior uveitis. Complementary tests to rule out other causes of uveitis resulted to be negative, except for HLA-B27, which tested positive. Response to treatment with topical corticosteroids and cyclopentolate was favorable. As IFN-α2b is considered an immune enhancer and has been widely associated with autoimmune side effects, topical therapy with IFN-α2b was temporally ceased until intraocular inflammation resolved. Topical IFN-α2b was resumed, and during follow-up, no signs of uveitis were detected. The main hypothesis is that IFN-α2b acts as a trigger for intraocular inflammation in individuals with uveitis predisposition. CONCLUSIONS: Topical IFN-α2b could trigger intraocular inflammation in patients with uveitis susceptibility. It may be reasonable to use IFN-α2b cautiously in patients with a known history of uveitis or uveitis predisposition.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Uveíte Anterior , Masculino , Humanos , Pessoa de Meia-Idade , Antígeno HLA-B27/uso terapêutico , Interferon-alfa/efeitos adversos , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Uveíte Anterior/induzido quimicamente , Uveíte Anterior/diagnóstico , Uveíte Anterior/tratamento farmacológico , Inflamação/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico
9.
Ocul Surf ; 28: 108-114, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36592780

RESUMO

PURPOSE: To assess the efficacy of topical interferon α-2ß(IFN) eye drops as a primary treatment for ocular surface squamous neoplasia(OSSN) and evaluate factors that impact response to treatment and recurrence of OSSN. METHOD: A retrospective study of 143 OSSN patients treated with topical IFN(1MIU/ml) from January 1998 to June 2021. The diagnosis was based on clinical examination and anterior segment optical coherence tomography, with histologic confirmation was present in 46.2% of patients. Data on demographic, tumor characteristics, treatment outcome, and side effects were collected. The primary outcomes were tumor resolution frequency and recurrence rate. Secondary outcomes were predictive factors for resolution and recurrence and side effects of treatment. RESULT: Participants were mostly older (mean age, 69 years, SD 12.9, range 29-97), white(89%) males (74%). Complete tumor resolution was achieved in 80.4% of individuals with a mean time to resolution of 4.2 months (SD 2, range 0.5-12.3 months). On multivariable analysis, history of skin cancer (HR: 0.66, p = 0.05, 95%CI: 0.44-0.99) and immune system abnormalities (HR: 0.37, p = 0.009, 95%CI: 0.18-0.79) reduced the risk of tumor resolution, while a prior history of OSSN (HR: 3.49, p < 0.001, 95%CI: 1.76-6.93) increased the risk of resolution. With a mean follow-up time of 44.3 months (SD 50.9, 0-290 months), the recurrence rate was 0%, 2.3% and 3.1% at 1, 2, and 5 years respectively. Mild hyperemia(18.9%) and pain(10.6%) were the two most common side effects. CONCLUSION: Topical IFN eye drops are a safe and effective primary treatment modality for OSSN with a reasonable side effect profile.


Assuntos
Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Neoplasias Oculares , Masculino , Humanos , Idoso , Feminino , Antineoplásicos/uso terapêutico , Interferon alfa-2/uso terapêutico , Estudos Retrospectivos , Soluções Oftálmicas/uso terapêutico , Neoplasias Oculares/diagnóstico , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Interferon-alfa/efeitos adversos , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Resultado do Tratamento , Administração Tópica
10.
Int Ophthalmol ; 43(2): 371-380, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35857192

RESUMO

PURPOSE: This study was taken up to look into the various causes of recurrence, clinicopathological profile and final outcomes in recurrent cases of ocular surface squamous neoplasia (OSSN). METHODOLOGY: A prospective cohort study was conducted and total 18 patients were recruited. All patients were subjected to detailed history, comprehensive eye examination and imaging studies. A treatment plan was formulated based on the size and extent of the lesion. The primary outcome measure was complete response to treatment with no evidence of recurrence after12 months and secondary outcome measure was complication associated with each treatment modality. RESULTS: The common cause of recurrence in our study was misdiagnosis of the lesion as in 15 cases it was diagnosed as pterygium and in 03 cases it was actinic keratosis. Excision Biopsy with adjunctive cryotherapy was the preferred treatment modality followed by topical interferon-alpha 2b drop-in our study. We could achieve good outcomes in terms of complete response to the treatment in 16 cases. The complication associated with this treatment was minimal in our study as few patients complained redness and irritation which subsided after application of topical lubricants. There was no sign of recurrence even at 12 months of follow-up in all 18 cases. CONCLUSION: The current study provided clinicopathological characteristics and treatment outcomes in recurrent cases of OSSN. In our study, adopting appropriate treatment strategy, regular follow-up to assess the response to treatment and change over to new treatment plan in cases with inadequate response helped in achieving good outcomes in recurrent cases of OSSN.


Assuntos
Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Neoplasias Oculares , Humanos , Interferon alfa-2 , Neoplasias Oculares/diagnóstico , Centros de Atenção Terciária , Estudos Prospectivos , Estudos Retrospectivos , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/terapia , Neoplasias da Túnica Conjuntiva/tratamento farmacológico
11.
Eye (Lond) ; 37(5): 837-848, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35882984

RESUMO

Lymphoma of the conjunctiva is an ocular malignancy derived from clonal proliferation of lymphocytes. The majority of conjunctival lymphoma is extranodal marginal zone B-Cell lymphoma (EMZL), however diffuse large B-cell (DLBCL), follicular (FL), mantle cell (MCL) and T- cell subtypes are also seen. Clinical manifestations are non-specific, but include unilateral or bilateral painless salmon-pink conjunctival lesions. Approaches to treatment have centered around local immunomodulation, often with Interferon-α2b or Rituximab (anti-CD20 monoclonal antibody) with or without radiation. Although conjunctival lymphoma is generally considered an indolent disease, recent advances in next-generation sequencing have improved clinicians' ability to predict future recurrence or systemic disease through assessment of cytogenic and molecular features. In this paper, we review the classification, clinical features, diagnostic techniques, and emerging strategies for management and prognostication of conjunctival lymphomas.


Assuntos
Antineoplásicos , Neoplasias da Túnica Conjuntiva , Neoplasias Oculares , Linfoma de Zona Marginal Tipo Células B , Linfoma , Humanos , Linfoma/patologia , Rituximab/uso terapêutico , Túnica Conjuntiva/patologia , Antineoplásicos/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/terapia , Neoplasias da Túnica Conjuntiva/tratamento farmacológico
12.
Graefes Arch Clin Exp Ophthalmol ; 261(4): 1159-1166, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36255550

RESUMO

PURPOSE: We herein compare topical interferon alpha 2b (IFN-α2b) to topical mitomycin C (MMC) in the adjuvant management after excision of primary acquired melanosis with atypia (PAM) and melanoma of the conjunctiva/cornea (CM). METHODS: We included 25 tumors from 25 patients (six with PAM and 19 with CM). After surgical excision, four patients started with adjuvant IFN-α2b (two in combination with radiotherapy), 19 with MMC, and two with radiotherapy alone. Five patients were switched from initial MMC/radiotherapy to IFN-α2b during follow-up. Efficacy was assessed via time to tumor recurrence and initial therapy response. RESULTS: With initial IFN-α2b, three patients (3/4, two with additional radiotherapy) showed complete remission (follow-up: 1478-1750 days) and one recurrence (1/4) was noted after 492 days. With initial MMC, no recurrence was recorded in 15 of the 19 patients (follow-up: 99-4732 days). Five patients were switched from MMC or radiotherapy to IFN-α2b: two patients showed complete remission (2/5), while another two (2/5) experienced recurrences and remained without recurrence after repeated courses of IFN-α2b (follow-up: 1798 and 1973 days). Only one patient showed incomplete response. Adverse effects were recorded in five patients, all received MMC. CONCLUSION: Topical IFN-α2b (arguably together with radiotherapy) may be a viable alternative to MMC in PAM and CM. We observed fewer side effects at similar response rates. However, when response to MMC was poor, IFN-α2b may also be of limited utility.


Assuntos
Neoplasias da Túnica Conjuntiva , Melanose , Humanos , Mitomicina , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Melanose/diagnóstico , Melanose/tratamento farmacológico , Recidiva Local de Neoplasia , Interferon-alfa/uso terapêutico , Adjuvantes Imunológicos
13.
J Cancer Res Clin Oncol ; 149(8): 4305-4314, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36074189

RESUMO

PURPOSE: Since there is a lack of clear information regarding the benefit to combine supportive therapies (such as artificial tears) to mitomycin C (MMC) in the treatment of ocular surface neoplasia, the primary purpose of the study was to evaluate hyaluronic acid eye drops and hyaluronic acid-conjugated lactobionic acid (LACTOyal FREE) eye drops as supportive therapy. METHODS: Retrospective evaluation of patients with ocular surface squamous neoplasia or conjunctival melanocytic tumor treated with MMC, who had used also artificial tears as supportive treatment. A 6-month follow-up with evaluation of subjective and objective tests for ocular surface integrity was conducted. RESULTS: A total of 35 patients were analyzed, most of them with squamous disease (71.4%). The break-up time (BUT), Ocular Surface Disease Index (OSDI) and Schirmer test values showed a significant difference at any time point with overall population. No statistical difference was found among subgroups (Lactoyal vs No Lactoyal). CONCLUSION: The use of an ancillary therapy based on hyaluronic acid allows to improve both subjective and objective ocular parameters, reducing MMC induced adverse effects. Meantime, hyaluronic acid-conjugated lactobionic acid eye drops highlighted the same advantages with a more positive trend in OSDI results.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Neoplasias Oculares , Humanos , Mitomicina/farmacologia , Mitomicina/uso terapêutico , Lubrificantes Oftálmicos/uso terapêutico , Ácido Hialurônico/uso terapêutico , Estudos Retrospectivos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/induzido quimicamente , Neoplasias da Túnica Conjuntiva/patologia , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/induzido quimicamente , Neoplasias Oculares/patologia
14.
J Oncol Pharm Pract ; 29(4): 975-979, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36131486

RESUMO

PURPOSE: To report the efficacy and safety of 5-fluorouracil as the second line of treatment for two cases of conjunctival intraepithelial neoplasia refractive to topical interferon alpha-2b. CASE REPORT: In the first case, a 77-year-old woman was evaluated because of a fleshy vascularized lesion in the temporal conjunctiva on her right eye with leukoplakia of the corneal epithelium from 10- to 5-o'clock limbus. In the second case, an 81-year-old man, a nodular lesion in the temporal conjunctiva on his RE, with corneal adjacent opalescence, one millimeter in extent, was observed. Both patients were initially treated with excisional surgery, the samples being reported as conjunctival intraepithelial neoplasia with high-grade dysplasia. Co-adjuvant treatment with topical interferon alpha-2b 1 mIU/mL was indicated 4 times/day uninterruptedly. In the first case, there was no response despite 8 months of treatment, while in the second, the corneal lesion progressed in an arboriform pattern after 4 months of topical chemotherapy. MANAGEMENT & OUTCOME: In the absence of efficacy, the treatment was then changed to topical 5-fluorouracil (1%), 4 times/day for 7 days with a time-lapse of 21 days off, which constitutes a course. Two and four courses of treatment with 5-fluorouracil 1% were completed in both cases in the absence of important side effects. After the first course, both patients showed complete remission of the lesions. No clinical signs of relapse were noted after 1 year of follow-up. DISCUSSION: The treatment with 5-fluorouracil is a good option as the second line of treatment for conjunctival intraepithelial neoplasia who are low-responders to interferon alpha-2b, with fewer side effects than other currently available alternatives.


Assuntos
Antineoplásicos , Neoplasias da Túnica Conjuntiva , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Interferon alfa-2/uso terapêutico , Interferon-alfa/efeitos adversos , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Fluoruracila/efeitos adversos , Administração Tópica , Resultado do Tratamento , Proteínas Recombinantes/uso terapêutico
15.
Ocul Surf ; 27: 67-74, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36476665

RESUMO

PURPOSE: To determine the efficacy and safety of topical 1% 5-fluorouracil (5FU) eye drops as primary treatment of ocular surface squamous neoplasia (OSSN). METHODS: Patients were diagnosed with OSSN based on slit-lamp examination and anterior segment optical coherence tomography (AS-OCT). In ambiguous cases an incisional biopsy was performed. All were treated with 5FU eye drops as primary therapy and retrospectively reviewed. Data on demographics, tumor characteristics, treatment outcome, and side effects were collected. The primary outcome measures were resolution frequency and recurrence rate of OSSN. Secondary outcomes were risk factors for resolution and recurrence, and side effects of treatment. RESULTS: The mean age of 251 subjects (258 eyes) was 67.5 ± 11.7 years, 182 were male. Patients were followed up on average for 752 ± 580 days. Overall, 87% of patients experienced complete tumor resolution. Multivariable analysis revealed that superior tumor location (HR: 0.62, 95% CI: 0.41-0.93, p = 0.02) and leukoplakia (HR: 0.65, 95% CI: 0.41-0.93, p = 0.02), decreased the likelihood of tumor resolution. The recurrence rate was 4% at six months, 8% at one year, and 19% at two years. Larger tumor area increased chances of tumor recurrence (HR: 1.01, 95% CI: 1.00-1.02 p = 0.03). The most common side effects of 5-FU were mild hyperemia and pain, which occurred in 26% and 23% of patients, respectively. Among the sight-threatening side effects, limbal stem cell deficiency occurred in only 3% of patients. CONCLUSIONS: Topical 1% 5FU eye drops are a safe and effective medication for OSSN. Superior tumor location and leukoplakia decreased the chance of tumor resolution.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Neoplasias Oculares , Humanos , Masculino , Feminino , Seguimentos , Neoplasias Oculares/diagnóstico , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/patologia , Soluções Oftálmicas/uso terapêutico , Estudos Retrospectivos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Fluoruracila/uso terapêutico , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia
16.
Cancer Immunol Immunother ; 72(5): 1185-1198, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36367558

RESUMO

Ocular surface squamous neoplasia (OSSN) is the major cause of corneal cancer in man and horses worldwide, and the prevalence of OSSN is increasing due to greater UVB exposure globally. Currently, there are no approved treatments for OSSN in either species, and most patients are managed with surgical excision or off-label treatment with locally injected interferon alpha, or topically applied cytotoxic drugs such as mitomycin C. A more broadly effective and readily applied immunotherapy could exert a significant impact on management of OSSN worldwide. We therefore evaluated the effectiveness of a liposomal TLR complex (LTC) immunotherapy, which previously demonstrated strong antiviral activity in multiple animal models following mucosal application, for ocular antitumor activity in a horse spontaneous OSSN model. In vitro studies demonstrated strong activation of interferon responses in horse leukocytes by LTC and suppression of OSSN cell growth and migration. In a trial of 8 horses (9 eyes), treatment with topical or perilesional LTC resulted in an overall tumor response rate of 67%, including durable regression of large OSSN tumors. Repeated treatment with LTC ocular immunotherapy was also very well tolerated clinically. We conclude therefore that ocular immunotherapy with LTC warrants further investigation as a novel approach to management of OSSN in humans.


Assuntos
Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Neoplasias Oculares , Humanos , Cavalos , Animais , Interferon alfa-2/uso terapêutico , Carcinoma de Células Escamosas/patologia , Antineoplásicos/uso terapêutico , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Neoplasias da Túnica Conjuntiva/cirurgia , Interferon-alfa , Neoplasias Oculares/terapia , Imunoterapia , Estudos Retrospectivos
17.
Cornea ; 41(10): 1271-1275, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36107845

RESUMO

PURPOSE: The purpose of this study was to introduce the initial experience in the use of topical pegylated interferon alpha 2a (PegIFN-α-2a) for ocular surface squamous neoplasia (OSSN). METHODS: A retrospective medical record review of 8 eyes of 8 patients diagnosed with OSSN and treated with PegIFN-α-2a was performed. All cases were diagnosed of noninvasive OSSN both clinically and histologically. The pegIFN-α-2a was prescribed at a concentration of 20 µg/mL and applied 4 times a day for at least 3 months. RESULTS: In all 8 cases, topical PegIFN-α-2a was well-tolerated and did not lead to discomfort or any adverse side effects. It resulted in reduction in lesion size and extent in all cases and complete resolution of the lesions. CONCLUSIONS: Topical PegIFN-α-2a might be an effective and safe treatment option for noninvasive OSSN.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Doenças da Córnea , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Doenças da Córnea/patologia , Humanos , Interferon alfa-2/uso terapêutico , Interferon-alfa/efeitos adversos , Polietilenoglicóis/uso terapêutico , Estudos Retrospectivos
18.
Sci Rep ; 12(1): 14221, 2022 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-35987957

RESUMO

Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical pharmacotherapy agents such as 5-fluorouracil (5-FU), interferon alfa-2b (IFN) and mitomycin-C (MMC) are also commonly used. The protocol was registered (CRD42021224961). Comprehensive literature research was carried out to compare topical pharmacotherapy (5-FU or IFN or MMC) to surgical excision regarding clinical success (tumor resolution), recurrence and complications in patients undergoing treatment for OSSN. From 7859 records, 7 articles were included in the qualitative and 4 in the quantitative synthesis. The outcomes of surgical excision and topical pharmacotherapy were comparable in the included articles. There were no significant differences between surgical excision and topical pharmacotherapy regarding the clinical success [odds ratio (OR): 0.785; confidence interval (CI): 0.130-4.736, P = 0.792)] and tumor recurrence (OR: 0.746; CI: 0.213-2.609; P = 0.646). The most common side effect of the different therapeutic options was dry eye. The highest rate of dry eye symptoms was reported after surgical excision (in 59%). Topical pharmacotherapy with all the 3 agents is as effective and well-tolerable as surgical excision in terms of tumor resolution, recurrence rate and side effects in all OSSN patients suggesting similar long-term clinical benefits.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Neoplasias Oculares , Administração Tópica , Carcinoma de Células Escamosas/patologia , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Neoplasias da Túnica Conjuntiva/cirurgia , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/patologia , Neoplasias Oculares/cirurgia , Fluoruracila , Humanos , Interferon alfa-2 , Mitomicina , Estudos Retrospectivos , Resultado do Tratamento
20.
Transl Vis Sci Technol ; 11(7): 23, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35895055

RESUMO

Purpose: Conjunctival squamous cell carcinoma (SCC) is a sight-threatening ocular surface malignancy with the primary treatment modality being surgical resection. To evaluate surgical imaging modalities to improve surgical resection, we established a novel murine model for conjunctival SCC to demonstrate the utility of panitumumab-IRDye800, a fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibody. Methods: NOD-scid IL2Rgammanull (NSG) mice received subconjunctival injection of UM-SCC-1 or SCC-9, head and neck SCC cell lines. On tumor growth, mice were injected with Panitumumab-IRDye800CW, and imaged with a small animal imaging system and optical coherence tomography (OCT). Immunohistochemistry for SCC markers were used to confirm tumor origin. Results: Seventy-five percent (N = 4) of the UM-SCC-1 group developed aggressive, rapidly growing tumors that were P40 and EGFR positive within two weeks of inoculation. The SCC-9 tumors failed to demonstrate any growth (N = 4). Ocular tumors demonstrated high fluorescence levels with a tumor to background ratio of 3.8. Conclusions: Subconjunctival injections are an appropriate technique to create in vivo models for assessing treatment modalities and novel therapies in conjunctival SCC. Translational Relevance: This model demonstrates Panitumumab-IRDye800CW's utility in the ophthalmic setting and suggests that clinical trials may be warranted.


Assuntos
Neoplasias da Túnica Conjuntiva , Neoplasias de Cabeça e Pescoço , Animais , Anticorpos Monoclonais/uso terapêutico , Linhagem Celular Tumoral , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Modelos Animais de Doenças , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Camundongos , Camundongos Endogâmicos NOD , Panitumumabe , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico
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