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Transplantation surgery becomes more widespread with time worldwide; organ transplantation increases the risk of developing malignancies. This phenomenon is primarily due to immunosuppressive treatment which is one of the mainstay approaches to prevent transplant rejection. It is aimed to describe clinical signs and symptoms of histologically proven ocular surface squamous neoplasia (OSSN) in renal transplant patients. Three patients, who previously underwent renal transplant surgery, diagnosed with OSSN are presented. The histopathological examination results were conclusive for squamous cell neoplasia in all cases. No recurrence in any patients was observed after total surgical excision, cryotherapy, and reconstruction with amniotic membrane. Solid organ transplant patients undergo intense immunosuppressive treatment to prevent transplant rejection. That immunosuppressive treatment increases the risk of developing secondary malignancies including OSSN. It is important to inform all transplant patients about these risks. Even though OSSN is known to be a relatively benign acting tumor that rarely metastasizes to distant organs, the clinical course might change if it develops in an immunocompromised patient. For this reason, these patients should be monitored for any formation of a mass on the ocular surface. Surgical management through complete excision can result in the complete resolution of a tumor.

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PURPOSE: To report the demographic profile, clinical presentation, and management outcomes of ocular surface squamous neoplasia (OSSN) treated with primary topical chemotherapy in a limited resource secondary eye care facility in rural parts of South India. METHODS: Retrospective interventional study of 38 eyes of 37 patients with OSSN treated with topical 1% 5-Fluorouracil (5FU), over a period of two years. RESULTS: The median age at presentation with OSSN was 44 years (mean, 46 years; range 13 to 74 years). Majority (76%) were males. The most common morphological variant was placoid OSSN (18, 47%). Limbus was the most common epicenter (31, 82%). Corneal OSSN was the most initially misdiagnosed variant (n = 3). Of the 38 eyes receiving one week on and 3-weeks off cycles of 5FU regimen, complete tumor resolution was achieved in 36 (95%) eyes. The median number of topical 5FU cycles for tumor resolution was 2 (mean, 2; range, 1 to 4). Over a median follow-up period of 5 months (mean, 6 months; range, 1 to 27 months), tumor recurrence was noted in 3 eyes (8%), of which one case had xeroderma pigmentosum with bilateral multifocal recurrence. Complication rate was 5% (n = 2), which included transient conjunctival hyperemia (n = 1), and bacterial keratitis (n = 1) which resolved with fortified antibiotics. CONCLUSION: Primary chemotherapy with topical 1% 5FU is a safe and effective management modality for OSSN at limited resource settings in rural India.

Asunto(s)

Carcinoma de Células Escamosas , Enfermedades de la Córnea , Fluorouracilo , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Adulto , India/epidemiología , Anciano , Adolescente , Adulto Joven , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Enfermedades de la Córnea/diagnóstico , Enfermedades de la Córnea/tratamiento farmacológico , Enfermedades de la Córnea/epidemiología , Neoplasias del Ojo/tratamiento farmacológico , Neoplasias del Ojo/epidemiología , Neoplasias del Ojo/diagnóstico , Neoplasias del Ojo/terapia , Antimetabolitos Antineoplásicos/uso terapéutico , Población Rural , Soluciones Oftálmicas , Neoplasias de la Conjuntiva/tratamiento farmacológico , Neoplasias de la Conjuntiva/terapia , Neoplasias de la Conjuntiva/patología , Neoplasias de la Conjuntiva/epidemiología , Estudios de Seguimiento

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The authors present a retrospective analysis of three cases of isolated corneal ocular surface squamous neoplasia (C-OSSN) without limbal or conjunctival involvement and review the clinical and anterior segment optical coherence tomography (AS-OCT) features, along with treatment outcomes. The mean age at presentation was 51 years (range: 32-64 years). The mean tumor diameter was 5 mm (range: 3-6.5 mm). All lesions were placoid with <1 mm thickness. One case had surface keratin. AS-OCT revealed hyperreflective epithelium with abrupt transition in all cases, with mean thickness of 118 µm (range: 60-162 µm). One patient underwent alcohol-assisted keratoepitheliectomy (AKE) and two patients received topical Interferon alpha-2B followed by AKE. Histopathology revealed mild squamous dysplasia in all. No tumor residue or recurrence was noted at a mean follow-up period of 2 years (range: 1-4 years). Isolated C-OSSN is rare. AS-OCT serves as a useful noninvasive tool for supporting the diagnosis of AKE yielding long-term favorable outcomes.

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Objective: To describe the morphological and histopathological features of primary conjunctival basal cell carcinoma (BCC) in a young adult Filipino. Introduction: Malignant conjunctival tumors arise from different cells, the most common of which are squamous cell carcinomas (SCCs), (including ocular surface squamous neoplasia [OSSN]), melanomas, and lymphomas. Primary conjunctival BCC is rare and can mimic the clinical features of OSSN. Only seven reported cases were published. Most cases are in the 6th-8th decades of life, and we report the first case in a young adult male. Case Summary: A 37/M, HIV-seronegative, presenting with a 3-year history of enlarging fleshy, pedunculated mass on the right eye measuring 8.5 mm × 8.0 mm at the superonasal limbus encroaching on the cornea, with prominent feeder vessels. Whitish-to-grayish plaques were observed on the surface of the lesions. Wide excision of the mass using the no-touch technique was performed under local anesthesia. Four cycles of mitomycin C (0.02%) were administered as chemoadjuvant therapy. Histopathology showed basaloid cells with peripheral palisading, most consistent with BCC. Immunohistochemistry was positive for Bcl-2 and CD10 markers and negative for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), confirming conjunctival BCC. Eight weeks postoperatively, fibrovascular tissue proliferation was noted at the excision site. Anterior segment-optical coherence tomography (AS-OCT) revealed a thickened hyperreflective band that was continuous with the epithelium, indicating possible recurrence. Resection with rush frozen section revealed fibrotic tissue that was negative for tumor cells. The bare sclera was covered with conjunctival autograft. There was no recurrence of the lesion after 16 months of follow-up. Conclusion: Primary BCC of the conjunctiva is rarely encountered, especially in young individuals, mimicking squamous neoplasia both in morphology and histopathology. Therefore, this should be considered in the differential diagnosis of OSSN. Immunostaining is crucial in differentiating between the two conditions and confirming the diagnosis. In most cases, wide surgical excision is sufficient. In addition, adjuvant therapies may be beneficial in preventing tumor recurrence.

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Purpose: To report clinical features and treatment outcome of three cases with isolated corneal intraepithelial neoplasia (CIN). Methods: This case series presents 3 patients with isolated CIN. Data collected included, presenting signs and symptoms including vision, anterior segment examination, medical and surgical outcomes and signs and symptoms at lost post-treatment visit. Results: Case 1 was a 45-year-old male who presented with an isolated grayish amoeboid corneal lesion which was excised with alcohol assisted epitheliectomy, he also received 6 cycles of topical mitomycin C (MMC) 0.02% and one injection of interferon alfa-2b with no recurrence during the 10-year follow-up period. Case 2 was 78-year-old male referred for a suspicious white corneal lesion which was completely excised, the patient also received 6 subconjunctival injections of interferon alpha-2b. However, the lesion recurred at 2.5-years post-treatment. Case 3 was a 63-year-old male patient who presented with an isolated corneal lesion that was excised using alcohol-assisted epitheliectomy, patient received four cycles of topical 5-fluorouracil with no recurrence at last follow-up visit at 6 months. Conclusion: Isolated corneal intraepithelial neoplasia (CIN) is a rare entity with few reported cases in the literature. In this case series, we report long and short-term management outcomes of combined surgical and medical therapy for isolated CIN.

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OBJECTIVE: To study the efficacy and side-effect profile of topical 5-Fluorouracil (5-FU) in the treatment of ocular surface squamous neoplasia (OSSN). METHODS: Retrospective study of 101 eyes of 100 patients treated with 5-FU with one week on and 3 weeks off regimen. RESULTS: Of the 100 patients (101 eyes), the mean age at diagnosis of OSSN was 49 (median, 52 years; range, 11-87 years). History of prior intervention was noted in 6 (6%) eyes. Tumor epicenter included bulbar conjunctiva (n = 54; 53%), limbus (n = 27; 27%), and cornea (n = 20;20%). Mean number of cycles of topical 5-FU administered was 3 (median, 3; range, 1-8). Complete tumor regression was achieved with topical 5-FU in 89 (88%) eyes with a mean number of 2 cycles (median, 2; range, 1-6) of 5-FU. The remaining 12 (12%) lesions underwent additional treatment including excisional biopsy (n = 7), extended enucleation (n = 3), and topical Interferon alpha 2b (n = 2) for complete tumor control. Over a mean follow-up period of 6 months (median, 5 months; range, 1-36 months) following treatment, tumor recurrence was noted in 2 (2%) patients, and side-effects were noted in 7 (7%) eyes including conjunctival hyperemia (n = 1), punctal stenosis (n = 1), sterile keratitis (n = 4), and limbal stem cell deficiency (n = 1). CONCLUSION: Topical 5-FU is an effective non-invasive therapy for OSSN with a minimal side-effect profile.

Asunto(s)

Antimetabolitos Antineoplásicos , Carcinoma de Células Escamosas , Fluorouracilo , Soluciones Oftálmicas , Humanos , Fluorouracilo/administración & dosificación , Estudios Retrospectivos , Anciano , Masculino , Persona de Mediana Edad , Femenino , Adulto , Anciano de 80 o más Años , Adolescente , Antimetabolitos Antineoplásicos/administración & dosificación , Adulto Joven , Soluciones Oftálmicas/administración & dosificación , Niño , Resultado del Tratamiento , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/diagnóstico , Administración Tópica , Neoplasias del Ojo/tratamiento farmacológico , Neoplasias del Ojo/diagnóstico , Neoplasias de la Conjuntiva/tratamiento farmacológico , Neoplasias de la Conjuntiva/diagnóstico , Neoplasias de la Conjuntiva/patología , Enfermedades de la Córnea/tratamiento farmacológico , Enfermedades de la Córnea/diagnóstico , Estudios de Seguimiento

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Introduction: This study examined the distribution of histopathological disease severity amongst a cohort of patients treated for clinically suspected ocular surface squamous neoplasia and evaluated the relationship between various patient and clinical factors and the severity of pathological grade as well as treatment outcomes. Methods: A retrospective cohort study of demographic and clinicopathological factors of 150 patients clinically diagnosed with suspected ocular surface squamous neoplasia who underwent excision of lesion with histopathological diagnosis. Results: The study included 125 cases; the mean age at diagnosis was 64 years (SD = 11.26). 74% of cases were histologically confirmed as ocular surface squamous neoplasia. Pathological distribution was conjunctival intraepithelial neoplasia I (13.6%), conjunctival intraepithelial neoplasia II (16.8%), conjunctival intraepithelial neoplasia III (21.6%), carcinoma in situ (21.6%), and squamous cell carcinoma (2.4%). Lesion appearance was leukoplakic (18%), gelatinous (15%), dysplastic (11%), vascular (6%), papilliform (2%), nodular (2%). Lesion location was nasal (43%), temporal (42%), and superior or inferior (14%). Recurrence occurred in 7 cases (5.6%). A significant association was found between presence of leukoplakia and pathological grade (p = 0.05). Conclusions: Ocular surface squamous neoplasia is most frequently diagnosed in conjunctival intraepithelial neoplasia III and carcinoma in situ stages, and treatment outcomes are usually favourable.

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PURPOSE: To assess the prevalence and subtypes of Human Papillomavirus (HPV) in Ocular Surface Squamous Neoplasia (OSSN) in Human Immunodeficiency Virus (HIV) positive and negative patients in South Africa. BASIC PROCEDURES: This study was a single center retrospective cross-sectional study, conducted at Tygerberg Hospital, Western Cape, South Africa. We assessed 63 histopathologically confirmed OSSN formalin-fixed paraffin-embedded (FFPE) tissue blocks from 2015-2023. The presence of HPV was determined using the Hybrispot Direct Flow Chip Kit. Corresponding clinical data was retrieved from the National Health Laboratory Service (NHLS) central data warehouse. MAIN FINDINGS: Of the confirmed OSSN samples, 66.7% tested positive for HPV (95% confidence interval [CI] 54-77.3%). Of the 42 HPV positive samples, 38 (90.5%) had one or more known genotypes detected and 4 had unknown genotypes. The most prevalent subtypes were HPV 11, 16 and 18 (found in 61.9%, 52.4% and 33.3% of HPV positive samples respectively). 88.9% of the lesions biopsied were from HIV positive patients, of whom 56.4% had a CD4 + count of < 200 cells/µL. A lower median CD4 + count was detected among HIV positive patients with invasive squamous cell carcinoma compared to those with moderate dysplasia (p < 0.0198). CONCLUSIONS: There is a high prevalence of HPV in OSSN in South Africa. Certain subtypes namely, 11, 16, 18, 31, 33 and 35 may be more carcinogenic. HIV with HPV co-infection may be linked as a causative factor in the development of OSSN.

Asunto(s)

Infecciones por VIH , Papillomaviridae , Infecciones por Papillomavirus , Humanos , Sudáfrica/epidemiología , Masculino , Femenino , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Prevalencia , Persona de Mediana Edad , Estudios Transversales , Estudios Retrospectivos , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Adulto , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Anciano , Neoplasias del Ojo/epidemiología , Neoplasias del Ojo/virología , Carcinoma de Células Escamosas/virología , Carcinoma de Células Escamosas/epidemiología , Genotipo , Virus del Papiloma Humano

RESUMEN

PURPOSE: To report an unusual case of ocular surface squamous neoplasia (OSSN) associated with human papilloma virus (HPV)-16 infection with an atypical morphology in a young otherwise healthy patient. CASE DESCRIPTION: A 17 year-old healthy male was referred to our department for evaluation of a corneal infiltrate with anterior stromal neovascularization in the right eye. One year before, the patient underwent an excision of a corneo-conjunctival lesion that was located inferiorly in the same eye. Histopathological analysis had shown moderate and severe dysplasia of the conjunctival epithelium and resulted positive for HPV-16. We performed a diagnostic incisional biopsy of the limbal conjunctiva and of the corneal epithelium for histological examination and molecular testing for HPV and Chlamydia by using polymerase chain reaction (PCR). Histopathologic evaluation demonstrated low-grade dysplasia of conjunctiva. PCR testing of the corneal epithelium was positive for HPV-16, similarly to the first biopsy performed by another centre. The patient was successfully treated with topical interferon alfa-2b (1,000,000 IU/ml) for a total of six months. After the treatment, the corneal infiltrate improved dramatically with regression of neovascularization and improvement of corneal transparency and vision. DISCUSSION: The present report described an atypical presentation of HPV-related OSSN due to its unusual morphology, young age of onset and absence of associated comorbidity. CONCLUSION: Conservative treatment with topical interferon-alpha 2b could be used to treat successfully HPV-16 positive OSSN, with no corneal irregularity or potential loss of vision compared to surgical excision.

Asunto(s)

Neoplasias de la Conjuntiva , Papillomavirus Humano 16 , Interferón alfa-2 , Infecciones por Papillomavirus , Humanos , Masculino , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Adolescente , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 16/genética , Interferón alfa-2/uso terapéutico , Interferón alfa-2/administración & dosificación , Neoplasias de la Conjuntiva/diagnóstico , Neoplasias de la Conjuntiva/virología , Neoplasias de la Conjuntiva/patología , Infecciones Virales del Ojo/diagnóstico , Infecciones Virales del Ojo/virología , Infecciones Virales del Ojo/tratamiento farmacológico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/virología , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Reacción en Cadena de la Polimerasa , ADN Viral/análisis , ADN Viral/genética , Biopsia , Neoplasias del Ojo/diagnóstico , Neoplasias del Ojo/tratamiento farmacológico , Neoplasias del Ojo/virología , Neoplasias del Ojo/cirugía

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Purpose: To explore the role of ultraviolet radiation (UVR) in the occurrence and development of various ocular malignancies. Methods: In this article, we retrieved ocular malignancy data from the Global Cancer Observatory (GCO) and performed correlation analysis with the global UV index and sunshine duration. We searched for associated studies using the following databases: Embase, Pubmed, Cochrane Library, and Google Scholar. We conducted the literature by searching the Mesh terms denoting an exposure of interest ("UV radiation", "ultraviolet rays", and "ocular malignancies", All studies included are published until December 30, 2023 without language restrictions. Results: The mechanisms and epidemiological statistics of UVR on the onset and progression of eyelid malignancies are the most studied and clear. The role of UVR in conjunctival melanoma is similar to that in eyelid melanoma. The relationship between uveal melanoma and UVR is controversial, however, it may have at least a certain impact on its prognosis. UVR causes ocular surface squamous neoplasia by further activating HPV infection. Conclusions: UVR is a decisive risk factor for ocular malignancies, but the incidence of ultraviolet-induced tumors is also affected by many other factors. A correct and comprehensive understanding of the mechanisms of UVR in the pathogenesis of ocular malignant tumors can provide patients with more effective and selective immune regulation strategies.

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We present the case of a 27-year-old male who presented to our ophthalmology outpatient clinic with a pigmented lesion on the conjunctiva of his right eye. There was no history of ocular trauma or familial ocular complaints, and a thorough evaluation revealed the patient's seropositive status for HIV for the past eight years. The presentation resembled a conjunctival pigmentary lesion, with typical features of ocular surface squamous neoplasia (OSSN) being absent and a demographic incongruent with typical OSSN cases as OSSN typically affects the elderly population. Given the patient's HIV status and the lesion's recent increase in size, a more aggressive treatment approach was warranted. Mass excisional biopsy surgery confirmed conjunctival intraepithelial neoplasia with one positive margin. Adjuvant treatment with mitomycin eye drops (0.04%) resulted in no lesion recurrence at the one-month follow-up. Conjunctival intraepithelial neoplasia can mimic pigmentary lesions in young HIV-positive patients with obvious signs of OSSN being absent. In such cases, the history of seropositivity should be sufficient to suspect it as OSSN and aggressive management measures should be adopted to get best possible outcomes.

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PURPOSE: To analyze the efficacy, safety and cost-effectiveness of adjuvant therapy with 5-fluorouracil (5-FU) compared to interferon α-2b (IFNα-2b) after surgery in ocular surface squamous neoplasia (OSSN). METHODS: Retrospective study that included patients diagnosed with OSSN, who underwent surgical excision followed by adjuvant therapy with IFN α-2b (Group A) or 5-FU (Group B), in a tertial referral hospital. Clinical data collected included: demographics, risk factors, appearance, size and location of the lesions, slit-lamp examination, anterior segment optical coherence tomography, iconography and histological classification of subtypes of OSSN. Costs derived from surgery and adjuvant therapy were noted. Resolution of the lesion, recurrences and adverse events were studied. Cost-effectiveness analysis was performed with the incremental cost-effectiveness index (CEI). RESULTS: 54 cases of 54 patients were included, with a mean age of 74.4 years (range 28-109). 30 were male (55.6%), and predominantly Caucasian (79.6%). The main risk factor was prolonged sun exposure (79.6%). Leukoplakic appearance (48.1%), location in bulbar conjunctiva (48.2%) and T3 (46.3%) stage were the most common clinical features. Histologically, the percentage of CIN I, CIN II, CIN III and SCC were 25.9%, 29.6%, 40.7% and 3.7%, respectively. Complete resolution was obtained in 74.1% and tolerance was overall positive. The cost was significantly higher for IFNα (1025€ ± 130.68€) compared to 5-FU (165.57€ ± 45.85 €) (p 0.001). The CEI was - 247.14€. CONCLUSIONS: Both 5-FU and IFN α-2b are effective and present a good security profile as adjuvant therapies after surgery in OSSN. Although presenting slightly more ocular complications, 5-FU can be considered more cost-effective than IFN α-2b.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de la Conjuntiva , Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Análisis Costo-Beneficio , Centros de Atención Terciaria , Fluorouracilo/uso terapéutico , Análisis de Costo-Efectividad , Estudios Retrospectivos , Interferón-alfa/uso terapéutico , Interferón alfa-2/uso terapéutico , Conjuntiva , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/cirugía

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Ocular surface squamous neoplasia (OSSN) represents the most common conjunctival tumor in horses and frequently results in vision loss and surgical removal of the affected globe. Multiple etiologic factors have been identified as contributing to OSSN progression, including solar radiation exposure, genetic mutations, and a lack of periocular pigmentation. Response to conventional treatments has been highly variable, though our recent work indicates that these tumors are highly responsive to local immunotherapy. In the present study, we extended our investigation of OSSN in horses to better understand how the ocular transcriptome responds to the presence of the tumor and how the ocular surface microbiome may also be altered by the presence of cancer. Therefore, we collected swabs from the ventral conjunctival fornix from 22 eyes in this study (11 with cytologically or histologically confirmed OSSN and 11 healthy eyes from the same horses) and performed RNA sequencing and 16S microbial sequencing using the same samples. Microbial 16s DNA sequencing and bulk RNA sequencing were both conducted using an Illumina-based platform. In eyes with OSSN, we observed significantly upregulated expression of genes and pathways associated with inflammation, particularly interferon. Microbial diversity was significantly reduced in conjunctival swabs from horses with OSSN. We also performed interactome analysis and found that three bacterial taxa (Actinobacillus, Helcococcus and Parvimona) had significant correlations with more than 100 upregulated genes in samples from animals with OSSN. These findings highlight the inflammatory nature of OSSN in horses and provide important new insights into how the host ocular surface interacts with certain microbial populations. These findings suggest new strategies for the management of OSSN in horses, which may entail immunotherapy in combination with ocular surface probiotics or prebiotics to help normalize ocular cell and microbe interactions.

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Xeroderma pigmentosum (XP) is a rare, autosomal recessive disorder characterized by defective DNA repair. Patients with this disorder are at increased risk of developing various oculocutaneous malignancies. We report a rare case of a child with XP with bilateral ocular surface squamous neoplasia (OSSN) and left eye (OS) medial canthal basal cell carcinoma (BCC). Ultrasound biomicroscopy and contrast-enhanced computed tomography (CECT) of the orbit showed intraocular extension with no orbital involvement. The patient was started on topical interferon therapy in both eyes for OSSN. Topical 5% imiquimod was started for BCC for eight hours a day and then washed off. During follow-up, there was no recurrence of tumors. Since ocular and cutaneous neoplasms tend to occur at an early age in XP with a high rate of recurrence and they tend to be more aggressive, multimodal therapy with long-term follow-up is more advantageous for these patients. Topical 5% imiquimod can be used as a treatment for periocular BCC as an alternative to excision.

RESUMEN

IMPORTANCE: Ocular surface squamous neoplasia (OSSN) is a spectrum of malignancies that generally includes conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). OSSN can be treated with topical therapies including interferon α-2b (IFN), mitomycin C (MMC), or 5-fluorouracil 1% (5FU). Recently, due to unavailability of IFN and toxicity associated with MMC, therapy has shifted towards 5FU. OBJECTIVE: Herein, we compare the use of 5FU 1% as a primary versus (vs) secondary treatment regimen in eyes with moderate to extensive OSSN. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study of 73 consecutive patients with unilateral moderate to extensive OSSN treated at a single tertiary ocular oncology center from 2016 to 2023. Mean follow up time was 478.2 days overall, with 283.0 days for primary 5FU group and 860.3 days for secondary 5FU group. INTERVENTION: Topical 5FU 1% 4 times daily for 2 weeks with option for 2-weekly extension until tumor control, either as primary treatment or as secondary treatment to surgical resection, topical IFN or topical MMC, or cryotherapy. MAIN OUTCOMES: Outcome measures included tumor response, need for additional surgery, complications, and visual outcomes. RESULTS: A comparison (primary vs secondary treatment) revealed no difference in mean tumor basal dimension (19.6 vs 17.2 mm, P = 0.46), thickness (3.7 vs 3.4 mm, P = 0.64), or tumor extent (4.4 vs 4.5 clock hours, P = 0.92). The primary treatment group showed greater complete tumor control (77% vs 38%, P = 0.04). Multivariable analysis comparison (primary vs secondary treatment) showed primary treatment more likely to achieve complete tumor control (P = 0.01). There was no difference in the complication rate from 5FU treatment between the groups. There was no difference in visual outcome, and no tumor-related metastasis (0%) or death (0%). CONCLUSION AND RELEVANCE: Topical 5FU 1% is efficacious and safe as a primary or secondary treatment for moderate to extensive OSSN. Tumors treated with primary 5FU 1% demonstrated more complete resolution. In patients with moderate to extensive OSSN, primary treatment with topical 5FU 1% may be warranted.

Asunto(s)

Antimetabolitos Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias de la Conjuntiva , Fluorouracilo , Humanos , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias de la Conjuntiva/tratamiento farmacológico , Neoplasias de la Conjuntiva/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Antimetabolitos Antineoplásicos/administración & dosificación , Soluciones Oftálmicas/administración & dosificación , Adulto , Anciano de 80 o más Años , Administración Tópica , Resultado del Tratamiento , Estudios de Seguimiento

RESUMEN

PURPOSE: Chronic inflammation is a predisposing factor for metaplastic changes and ultimately dysplasia. We describe cases of OSSN occurring in the setting of chronic ocular surface inflammation. METHODS: Sixteen eyes from 14 individuals were included from one ocular oncology clinic between 2010 and 2023. Patients presented with ocular surface squamous neoplasia (OSSN) in the setting of chronic inflammation. The diagnosis of OSSN was made using anterior segment high-resolution optical coherence tomography (HR-OCT) and confirmed by histopathological analysis in all cases. RESULTS: Median age on presentation was 61 [IQR 47.5-69.2] years. Eleven (86%) individuals were male and five (36%) identified as White Hispanic. Ten eyes were referred with ocular surface diagnoses including pannus (n = 4), scarring (n = 3), pterygium (n = 2), and herpetic keratitis (n = 1). Only six eyes were referred as possible neoplasia. All individuals had a history of ocular surface inflammation. The most common inflammatory conditions were ocular rosacea (seven individuals) and atopic keratoconjunctivitis (AKC) (five individuals). Two individuals were found to have bilateral OSSN, one in the setting of ocular rosacea and the other in the setting of AKC. All 16 eyes from 14 individuals were suspected to have OSSN based on HR-OCT findings which guided the location of the incisional biopsies that subsequently confirmed histopathological diagnosis in all cases. CONCLUSION: OSSN may arise in the setting of chronic inflammation on the ocular surface. Identification of the tumor can be challenging in these cases, and HR-OCT can be a key diagnostic tool in detecting OSSN.

Asunto(s)

Tomografía de Coherencia Óptica , Humanos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Factores de Riesgo , Tomografía de Coherencia Óptica/métodos , Enfermedad Crónica , Estudios Retrospectivos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/diagnóstico , Neoplasias del Ojo/patología , Neoplasias del Ojo/diagnóstico , Inflamación/patología , Neoplasias de la Conjuntiva/patología , Enfermedades de la Córnea/patología , Enfermedades de la Córnea/diagnóstico , Enfermedades de la Córnea/etiología

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INTRODUCTION: Ocular surface squamous neoplasia (OSSN) may have atypical or unusual presentations and may attain large sizes especially in cases of delayed presentation resulting in late diagnosis, treatment, and eventual guarded visual prognosis. We are reporting an interesting cases series of OSSN with variable clinical presentations to highlight the importance of the pre-operative clinical judgment and tissue diagnosis. PRESENTATION OF CASES: Six patients (4 females and 2 males; mean age 59 years; range 42-79 years) were included with suspicious conjunctival lesions. The maximum dimension of the lesions was 17 mm. The initial suspected pre-operative clinical diagnosis -other than OSSN- included pterygium/pinguecula (n = 2), benign squamous papilloma (n = 1), cyst versus pyogenic granuloma (n = 1), and lymphoma (n = 1). This work has been reported in line with the PROCESS criteria. DISCUSSION: The final histopathological diagnosis was unexpectedly invasive squamous cell carcinoma (SCC) in 4, one SCC in-situ, and squamous dysplasia in one. The primary treatment included MMC 0.02 % for 2 cycles for chemo-reduction in one of the cases where OSSN was suspected. Excisional biopsy was performed eventually for all lesions with application of one or more of the following modalities: MMC 0.02 %, absolute alcohol 99 %, and cryotherapy to the conjunctival margin. No tumor recurrence was noted in any of the patients after an average period of follow-up of 26 months. Even though the outcome was good, tumor-related morbidity and delay in the referral by general ophthalmologists are to be considered. CONCLUSION: Conjunctival OSSN has wide presentation clinically and can be challenging in terms of diagnosis. Histopathological evaluation is essential for a definitive diagnosis and treatment. Accurate clinical diagnosis might affect the management plan with consideration for topical therapeutic modalities, however, these cases are best managed by wide excision using the no-touch technique and double-freeze-thaw cryotherapy to the conjunctiva with consideration of topical chemotherapy.

RESUMEN

INTRODUCTION: Ocular surface squamous neoplasia (OSSN) is the most common ocular malignancy; the pathophysiology is influenced by molecular, genetic, and epigenetic mechanisms. The incidence of OSSN is associated with the anatomy and physiology of the ocular surface, limbal stem cell configuration, limbal vulnerability, cancer stem cells, dysplasia, neoplasia, angiogenesis, invasion, and metastasis. The key etiological factors involved are human papillomavirus (HPV), human immunodeficiency virus (HIV), immunosuppression, p53 tumor suppressor gene, hypovitaminosis A, and failure of Deoxyribonucleic acid (DNA) repair mechanisms. AREAS COVERED: This special report is a focussed attempt to understand the molecular mechanism, genetic and epigenetic mechanism, and diagnostic modalities for OSSN. EXPERT OPINION: While these mechanisms contribute to genome instability, promoter-specific hypermethylation might facilitate and promote tumor formation by silencing tumor suppressor genes. OSSN understanding has improved with increased literature available on various genetic, molecular, and epigenetic mechanisms, although the exact genetic and epigenetic mechanisms still need to be elucidated. It is important to note that the molecular mechanisms of OSSN can vary among individuals, and further research is required to elucidate the underlying processes fully. Understanding these mechanisms is crucial for the development of targeted therapies and improved management of OSSN.

RESUMEN

Purpose: To report a case of high-risk human papillomavirus (HPV)-associated corneal/conjunctival intraepithelial neoplasia (CIN) in a 17-year-old fair-skinned male with no other risk factors. Observations: A 17-year-old Caucasian male presented with an 18-month history of left eye pain, redness, itchiness, and decreased vision. Examination revealed a leukoplakic nasal limbal/peripheral corneal lesion resistant to topical antibiotic and anti-inflammatory treatments. Excisional biopsy confirmed the diagnosis of CIN, and RNA in situ hybridization testing for high-risk HPV types 16/18 was positive. Subsequent testing of the patient for human immunodeficiency virus (HIV) returned negative. Conclusions and Importance: The median age of CIN diagnosis in the United States is in the sixth decade of life and is usually associated with a history of ultraviolet (UV) light exposure. There are reports of CIN in young patients with systemic immunodeficiency, immunosuppression, xeroderma pigmentosum, atopic dermatitis, asthma, and vaping. Here we present a case of high-risk HPV-associated CIN in a young, fair-skinned patient with no other identifiable risk factors.