[Severe Conjunctival and Corneal Epithelial Dysplasia: A Case Series]. / Schwere konjunktivale und korneale epitheliale Dysplasie: eine Fallserie.

BACKGROUND/OBJECTIVES: Ocular surface squamous neoplasia (OSSN) are among the most frequent non-pigmented malignancies of the ocular surface. They have a wide range of histological characteristics - ranging from mild epithelial dysplasia to invasive carcinoma of the squamous cells of the cornea. They may be restricted to the conjunctiva or also involve the cornea. As there are no leading symptoms in the early stages, diagnosis may be very delayed in patients who do not receive regular ophthalmological treatment. The present case series describes clinical and histological data on OSSN and includes clinical and histological data on OSSN, including possible clinical presentations, important risk factors, special histological and cytological features and therapeutic options. METHODS: Retrospective case series of patients with histologically confirmed severe epithelial dysplasia of the conjunctiva and cornea consistent with OSSN who presented to the Department of Ophthalmology in Basel University Hospital. The analysis covered demographic data, symptoms, diagnostic testing (photo documentation, brush biopsy), treatment and cytological and/or histological material and findings. RESULTS: We report on five patients aged between 41 and 92 years at the time of diagnosis. The histological findings in all patients included severe epithelial dysplasia, but with a heterogenous clinical presentation. In all cases, the lesion started in the conjunctiva, but traversed the limbus and extended to the cornea. The primary treatment was always surgical removal. In one patient, this had to be repeated several times due to recurrent metaplasia and was complemented by subsequent mitomycin C therapy. The clinical outcome ranged between total restitution of the original state to inevitable enucleation. CONCLUSION: The clinical presentation of OSSN is highly heterogenous, so that the initial diagnosis is difficult. There are no official guidelines for treatment, so that the treatment of choice varied between clinics. Regular ophthalmological follow-ups are recommended, even after complete surgical excision. Possible relevant concomitant diseases and risk factors must be identified before therapy.

Targeted Therapy and Immunotherapy for Advanced Malignant Conjunctival Tumors: Systematic Review.

PURPOSE: To review the outcomes of targeted therapy and immunotherapy in advanced conjunctival tumors, including conjunctival squamous cell carcinoma, conjunctival melanoma, and conjunctival lymphoma. METHODS: A Pubmed database systematic search was performed between January 1999 and December 2022. The literature search was limited to studies published in English. RESULTS: This review included 142 patients with advanced malignant conjunctival tumors from 42 articles. In the conjunctival squamous cell carcinoma group, 2 cases of advanced conjunctival squamous cell carcinoma treated with epidermal growth factor receptor inhibitors showed significant tumor size improvement after 7.5 months of follow-up. Among 7 cases treated with systemic immunotherapy, 5 cases (72%) had complete response (CR), 1 case (14%) showed partial response (PR), and 1 case (14%) had stable disease (SD) after 16 months. In the conjunctival melanoma group, among 18 cases treated with combined v-raf murine sarcoma viral oncogene homolog B1/mitogen-activated extracellular signal-regulated kinase inhibitors, 6 (33%) had CR, 5 (28%) had PR, 2 (11%) had SD, and 5 (28%) had progressive disease after 24.8 months of follow-up. Of 44 conjunctival melanoma cases treated with immunotherapy, 12 (28%) had CR, 9 (20%) had PR, 7(16%) had SD, and 16 (36%) had progressive disease after 14.2 months. Systemic Rituximab treatment for conjunctival lymphoma cases resulted in CR in 21 patients (63%), PR in 11 patients (33%), and SD in 1 patient (3%) after 20.5 months of follow-up. Intralesional Rituximab injections in 38 conjunctival lymphoma cases showed CR in 28 patients (75%), PR in 7 patients (19%), SD in 1 patient (2%), and progressive disease in 2 patients (4%) after 20.4 months of follow-up. CONCLUSIONS: Despite limited clinical case reports and short-term follow-ups, targeted therapy and immunotherapy have shown promising results for advanced malignant conjunctival tumors.

Factors affecting recurrence and metastasis in conjunctival melanoma.

PURPOSE: To evaluate clinical and demographic characteristics and factors affecting recurrence, metastasis, and survival in conjunctival melanoma (CM). METHODS: The clinical records of 45 patients who were treated for CM between October 1998 and June 2022 were retrospectively evaluated. Age, gender, presence of underlying conjunctival nevus-primary acquired melanosis (PAM), tumor stage according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, tumor basal diameter, tumor thickness, lymph node (LN) involvement, metastasis, presence of tumor at the surgical margin, treatment method, need for adjuvant therapy, local tumor control, recurrence, and survival were recorded. RESULTS: Twenty-one (46.7%) patients were female and 24 (53.3%) patients were male. The mean age at diagnosis was 53.2 ± 16.1 years. Median follow up time was 12 (1-300) months. Fifteen (33.3%) patients had conjunctival PAM; 2 (4.4%) patients had conjunctival nevus. The tumor stage was T1 in 24 (55.8%), T2 in 13 (30.2%), and T3 in 6 (14.0%) of the cases. The T stage in 2 cases could not be determined. For stage T1 and T2 CM, in addition to excisional biopsy (EB) and cryotherapy, alcohol epitheliectomy (AE) was performed in 17 cases (37.8%), superficial sclerectomy (SS) was performed in 7 (15.6%), and amnion membrane transplantation (AMT) due to a large conjunctival defect in 9 (20.0%). Six (14.0%) T3 cases underwent primary exenteration. Positive surgical margins were observed in 23 (51.1%) of the excised tumors at histopathologic examination. Adjuvant topical mitomycin-C (MMC) was used in 7 (30.4%) and strontium-90 episcleral brachytherapy in 4 (17.4%) of the 23 cases with tumor-positive borders. During the follow-up, recurrence was seen in 14 (31.1%) cases. According to Kaplan Meier analysis, the mean time to recurrence development was 90.5 ± 16.1 months and the 5-year recurrence free rate was 52.0%. Fourteen of the recurrent cases underwent EB + cryotherapy, 3 underwent AE + SS, and 3 underwent secondary exenteration. Metastasis and LN involvement occurred in 11 (24.4%) and 8 (17.8%) of the cases, respectively. Four (8.9%) cases expired during follow-up. According to Kaplan-Meier analysis, the mean time to metastasis was 106.2 ± 17.3 months and the 5-year metastasis free rate was 52.0%. While recurrence was more frequent in CM developing from PAM/nevus, metastasis was more frequent in men and those with LN involvement. CONCLUSION: Conjunctival melanoma was a malignant tumor with high recurrence and metastasis rates. Precursor nevus/PAM is a risk factor for recurrence, while male gender and regional LN involvement were risk factors for metastasis in this study.

Clinicopathological profile, management and clinical outcomes in recurrent cases of ocular surface squamous neoplasia at a tertiary care centre.

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.

Conjunctival Lymphoma.

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.

[Conjunctival Degeneration and Neoplasia]. / Bindehautdegenerationen und -neoplasien.

Conjunctival tumors result from gain of tissue, which can be either degenerative or neoplastic, but also inflammatory. In this article, degenerative (pterygium and pinguecula) as well as benign and malignant neoplastic conjunctival changes (epithelial, melanocytic and vascular tumors, choristomas as well as metastases) are discussed with regard to pathogenesis, symptoms, diagnostics and current status of treatment.

Primary Low Grade Follicular Lymphoma of the Conjunctivae Mimicking Nodular Anterior Scleritis: A Case Report.

Conjunctival lymphomas are rare entities and may present with non-specific ocular signs that resemble inflammation. They may mimic common ocular pathologies, leading to a delay in diagnosis and treatment. The treatment options of conjunctival lymphomas should be tailored to individuals due to their indolent nature compared to other adnexal lymphomas. Herein, the authors report a case of a primary follicular conjunctival lymphoma in a patient who presented with signs and symptoms of nodular anterior scleritis. The final histology of the conjunctiva lesion revealed primary follicular lymphoma. The patient was managed conservatively with active surveillance.

Ocular surface squamous neoplasia in Northern Thailand: a 16-year review.

PURPOSE: To evaluate clinical characteristics, treatments, and outcomes in patients with ocular surface squamous neoplasia (OSSN) at a tertiary center in Northern Thailand. METHODS: Patients diagnosed with either corneal-conjunctival intraepithelial neoplasia (CIN) or squamous cell carcinoma (SCC) from May 2000 to December 2015, were recruited. The patients' demographics, symptoms, clinical characteristics, cytopathology, treatments, and outcomes were reviewed. RESULTS: Overall 171 eyes from 168 patients, 92 eyes were CIN and 79 eyes were SCC. Males were affected in 65.5%. The mean age was 58.8 ± 16.8 (29-99) years. In most cases (60.3%), the tumors were located at the limbus. The most common clinical characteristic was papilliform appearance (46.2%). Human immunodeficiency virus (HIV) infection was found in 37 (22.0%) patients with a mean age of 40.5 ± 7.7 years. The treatments and outcomes were evaluated in 136 eyes whose main initial treatment was wide excision with adjunctive cryotherapy (47.8%), followed by topical mitomycin C (30.9%). The mean follow-up time after treatment was 20.8 ± 2.2 (3-110) months and the recurrence occurred in 18 eyes (13.2%) during the follow-up period. The mean recurrence-free time (months) for CIN was significantly longer than that of SCC (81.3 ± 10.0 [95%CI 61.5 - 101.1] vs 33.2 ± 4.6 [95%CI 24.0 - 42.3], p = 0.030). SCC was the only significant risk factor that influences the recurrence of the tumors with the adjusted hazard ratio of 5.69 (p = 0.005). CONCLUSION: OSSN in Northern Thailand usually involved a limbal area and presented as a papilliform mass. HIV infection should be suspected in young patients. CIN had better outcomes after treatments than invasive SCC.

Relapsed acute myeloid leukemia presenting as conjunctival myeloid sarcoma: a case report.

BACKGROUND: Conjunctival myeloid sarcoma (MS) as an isolated presentation of acute myeloid leukemia (AML) relapse is rare. Here, we report a case of unilateral conjunctival MS revealed as a sign of AML relapse. CASE PRESENTATION: A 50-year-old man with a history of AML in remission visited our clinic presenting with a left conjunctival injection persisting for 1 month. Diffuse subconjunctival thickening with conjunctival vascular engorgement was observed. Ultrasound biomicroscopy revealed a hyper-reflective, thickened conjunctiva in his left eye. During the incisional biopsy, the lesion was strongly attached to the underlying sclera; histopathologic examination revealed infiltration of leukemic blasts. The relapse of AML was confirmed by a successive bone marrow biopsy. The ocular lesion disappeared after allogeneic peripheral blood stem cell transplantation (PBSCT) and concomitant salvage radiotherapy on the left eye. The patient has remained in remission for 3 years after allogeneic PBSCT. CONCLUSIONS: Incidental conjunctival lesions can indicate AML relapse in patients treated earlier for AML. An ophthalmologist may have a role in the early detection of AML when a patient presents with an atypical conjunctival lesion.

New Therapeutic Approaches for Conjunctival Melanoma-What We Know So Far and Where Therapy Is Potentially Heading: Focus on Lymphatic Vessels and Dendritic Cells.

Conjunctival melanoma (CM) accounts for 5% of all ocular melanomas and arises from malignantly transformed melanocytes in the conjunctival epithelium. Current therapies using surgical excision in combination with chemo- or cryotherapy still have high rates for recurrences and metastatic disease. Lately, novel signal transduction-targeted and immune checkpoint inhibitors like cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, programmed cell death protein-1 (PD-1) receptor inhibitors, BRAF- or MEK-inhibitors for systemic treatment of melanoma have improved the outcome even for unresectable cutaneous melanoma, improving patient survival dramatically. The use of these therapies is now also recommended for CM; however, the immunological background of CM is barely known, underlining the need for research to better understand the immunological basics when treating CM patients with immunomodulatory therapies. Immune checkpoint inhibitors activate tumor defense by interrupting inhibitory interactions between tumor cells and T lymphocytes at the so-called checkpoints. The tumor cells exploit these inhibitory targets on T-cells that are usually used by dendritic cells (DCs). DCs are antigen-presenting cells at the forefront of immune response induction. They contribute to immune tolerance and immune defense but in the case of tumor development, immune tolerance is often prevalent. Enhancing the immune response via DCs, interfering with the lymphatic pathways during immune cell migration and tumor development and specifically targeting tumor cells is a major therapeutic opportunity for many tumor entities including CM. This review summarizes the current knowledge on the function of lymphatic vessels in tumor growth and immune cell transport and continues to compare DC subsets in CM with related melanomas, such as cutaneous melanoma and mucosal melanoma.

Ocular surface squamous neoplasia in India: a study of 438 patients.

PURPOSE: To describe the clinical features, histopathology, treatment, and outcomes of patients with ocular surface squamous neoplasia (OSSN) presenting to a referral centre in India. METHODS: Retrospective interventional study. RESULTS: Of 438 patients, the mean age at presentation was 49 years. Human immunodeficiency virus infection was noted in 72 (16%), xeroderma pigmentosum in 22 (5%), hepatitis B virus infection in 14 (3%), and systemic cancer in 8 (2%) patients. Tumor pigmentation was noted in 243 (54%) tumors with a mean percentage of tumor pigmentation of 44% (median, 40%; range, 1 to 100%). Intraocular tumor extension was noted in 12 (3%), and orbital tumor extension in 16 (4%) eyes. Of the 381 treated lesions, excisional biopsy (n = 247; 65%) was the most common treatment modality. Of the 311 lesions with histopathology diagnosis of OSSN, invasive squamous cell carcinoma (n = 92; 30%) was the most common. Over a mean follow-up period of 11 months (median, 5 months; range, 1 to 108 months) in 368 patients, tumor recurrence was noted in 16 (4%) eyes, globe salvage was achieved in 341 (90%) eyes, vision salvage in 338 (89%) eyes, regional lymph node metastasis occurred in 9 (2%), and metastasis-related death in 9 (2%) patients. CONCLUSION: Pigmented OSSN is common in Asian Indian population. Appropriate management of OSSN is associated with good vision, globe, and life salvage rates in India.

Bilateral ocular surface squamous neoplasia: A study of 25 patients and review of literature.

PURPOSE: To describe the risk factors, clinical presentation, management, and outcomes of patients with bilateral ocular surface squamous neoplasia (OSSN). METHODS: Retrospective case series. RESULTS: Of the 25 patients with bilateral OSSN, the mean age at diagnosis of OSSN was 31 years (median, 24 years; range, 2-60 years). Risk factors for bilateral OSSN included xeroderma pigmentosum (n = 15, 60%), human immunodeficiency virus infection (n = 3, 12%), conjunctival xerosis (n = 1, 4%), and topical steroid use (n = 1, 4%). There were no identifiable ocular or systemic risk factors in 7 (28%) patients. Presentation was synchronous in 14 (56%) and metachronous in 11 (44%) patients. Tumor morphology was bilaterally similar in 12 (48%) patients. Histopathological examination (n = 36) revealed conjunctival intraepithelial neoplasia (CIN) grade 1 in 4 (8%); grade 2 in 7 (14%); carcinoma in situ in 5 (10%), and invasive carcinoma in 20 (40%). Primary management of OSSN (n = 49) included excisional biopsy (n = 31, 62%), topical immunotherapy (IFN α2B) (n = 11; 22%), topical Mitomycin C (MMC) (n = 3, 6%), enucleation (n = 1, 2%), orbital exenteration (n = 2, 4%), and plaque brachytherapy (PBT) (n = 1, 2%). One patient was lost to follow-up after detection of tumor in the second eye. Recurrent tumors were noted in 16 (32%) eyes and binocular globe salvage was achieved in 16 (64%) patients at a mean follow up of 41 months (median 30 months; range, 1-164 months). CONCLUSION: OSSN occurrence can be synchronous or metachronous. Meticulous examination of the fellow eye is important for an early diagnosis of OSSN.

Vitreoretinal lymphoma occurring after systemic chemotherapy for primary conjunctival diffuse large B cell lymphoma: A case report.

INTRODUCTION: Ocular adnexal lymphoma and vitreoretinal lymphoma are rare forms of non-Hodgkin lymphoma. They are regarded as distinct disease entities due to the differences in molecular mechanism, management, and outcome. We present a rare case of conjunctival diffuse large B cell lymphoma (DLBCL) that developed to vitreoretinal lymphoma after systemic chemotherapy. PATIENT CONCERNS: A 60-year-old man presented with a left salmon-colored conjunctival mass. DIAGNOSIS: A biopsy was performed, and histopathologic examination showed DLBCL. Immunohistochemical staining was positive for CD20 with increased κ to λ light chain ratio. INTERVENTIONS: Bone marrow biopsy also revealed DLBCL. Gallium-67 scintigraphy showed abnormal uptake only in the left orbital lesion. Ann Arbor stage was estimated as IV. The patient underwent systemic combination chemotherapy and immunotherapy. OUTCOMES: Four months after the last course of chemotherapy, primary conjunctival DLBCL relapsed, manifesting vitreous opacity. Diagnostic vitrectomy confirmed a diagnosis of vitreoretinal lymphoma. LESSONS: Conjunctival DLBCL and vitreoretinal lymphoma are both DLBCL. After systemic chemotherapy for conjunctival DLBCL, the lymphoma may relapse in intraocular sites as secondary vitreoretinal lymphoma.

Ocular surface squamous neoplasia at a tertiary eye facility, Southwestern Nigeria: a 10-year review.

BACKGROUND: Ocular surface squamous neoplasia (OSSN) is a low-grade malignancy arising from the squamous epithelium of the ocular surface AIM: To describe the clinical presentation, histological diagnoses, treatment, and outcome of treatment in patients with OSSN managed at a tertiary health facility. METHODS: Medical records of all patients with OSSN managed using a standardized treatment protocol over a 10-year period were reviewed. RESULTS: Eighty-six patients comprising 44 (51.2%) males and mean age of 48.2 ± 15.8 years were studied. The most common presentation was a fleshy growth in the eye in all patients, and 43 (50.0%) patients tested positive to human immunodeficiency virus. The right eye was affected in 44 (51.2%) patients with no bilateral tumors, and the medial limbus was involved in 28 (32.6%) patients. Morphologically, 40 (46.5%) patients had gelatinous growth, 24 (27.9%) patients were in Tis category while 30 (34.9%) patients were in T4 category. Twenty-eight (32.6%) patients received complete course of adjuvant topical mitomycin C (0.04%) while nine (10.5%) patients completed adjuvant systemic chemotherapy and external beam radiation. Overall, 61 (70.9%) patients had no tumor recurrence, seven (8.1%) patients had recurrent tumor, while the status of 18 (20.9%) patients was not known. CONCLUSION: OSSN occurs more commonly in younger age group in our studied population and is strongly associated with HIV seropositivity. Intraoperative cryotherapy in patients with carcinoma in situ and intraoperative cryotherapy with adjuvant topical mitomycin C in those with invasive SCC that is limited to the ocular surface are associated with low tumor recurrence.