Ocular Surface Squamous Neoplasia Following Keratoplasty in Xeroderma Pigmentosa: A Series of Seven Cases.

Purpose: To describe the clinical features and management of post-keratoplasty ocular surface squamous neoplasia (pk-OSSN) in patients with xeroderma pigmentosum (XP).Methods: Retrospective case series of seven patients with XP.Results: The mean age at diagnosis of pk-OSSN was 22 years (median, 21 years; range, 12 to 37 years). There were four males and three females. Full-thickness keratoplasty (n = 5) and Descemet stripping endothelial keratoplasty (n = 2) were performed for optical (n = 6) and therapeutic indications (n = 1). None of the patients had evidence of OSSN before or at the time of keratoplasty. The mean interval between keratoplasty and pk-OSSN was 44 months (median, 14 months; range, 3 to 109 months). The tumor epicenter was located at the limbus (n = 4), bulbar conjunctiva (n = 1) or cornea (n = 2). The mean dimension of the lesions was 12 mm (median, 11 mm; range, 6 to 18 mm). Treatment details included conjunctival/corneal tumor excision (n = 6), plaque brachytherapy (n = 3; 1 primary, 2 adjuvant) and extended enucleation (n = 1). One patient had tumor recurrence 18 months after OSSN treatment, which was treated with wide excisional biopsy. All patients are alive and free of disease over a mean follow-up period of 37 months (median, 37 months; range, 4 to 65 months).Conclusion: XP patients undergoing keratoplasty can develop OSSN several months to years after keratoplasty and require close follow-up for the same. Wide excisional biopsy with/without plaque radiotherapy is effective in the management of pk-OSSN.

Conjunctival cancer in people living with HIV.

PURPOSE OF REVIEW: Historically, conjunctival cancer has been associated with HIV particularly in sub-Saharan Africa. The human papilloma virus (HPV) has been implicated as a potential causative agent without conclusive evidence. This review covers recent evidence of the epidemiology, diagnosis and treatment of conjunctival cancer in people living with HIV (PLWH). RECENT FINDINGS: HIV infection has been attributed to 33% of squamous cell carcinoma of the conjunctiva in sub-Saharan Africa. Although clear evidence of the effect of immunodeficiency on conjunctival cancer risk has been demonstrated, the role of HPV on conjunctival cancer development is still unclear. Biomarkers such as the p16 protein are not always indicative of HPV infection. The Epstein-Barr virus (EBV) might potentially be another infectious agent of interest in the development of conjunctival cancer. There is some evidence of increased conjunctival cancer recurrence post treatment as well as increased probability of metastasis in PLWH. SUMMARY: Immunodeficiency increases the risk of conjunctival cancer in PLWH. Symptomatic screening of conjunctival cancer in PLWH should be encouraged. Research on HPV involvement should remain a priority and EBV considered as another etiologic agent of interest. More studies on treatment modalities in PLWH should be considered.

Solitary Conjunctivocorneal Plasmacytoma Arising After Cataract Surgery.

PURPOSE: To report a case of solitary plasmacytoma of the conjunctiva with corneal encroachment and to review the literature of all published cases. METHODS: A 70-year-old man presented with 1-month history of pain and watering in the right eye, 7 months after undergoing cataract surgery in the same eye. RESULTS: The mass was surgically excised. Pathology and immunohistochemistry were consistent with plasmacytoma. Staging studies found no evidence of systemic disease. CONCLUSIONS: To our knowledge, this is the first case of plasmacytoma in the literature to involve the cornea. This case was not associated with systemic disease. Surgical excision and brachytherapy remain options for cases without corneal involvement.

Human papillomavirus infection plays a role in conjunctival squamous cell carcinoma: a systematic review and meta-analysis of observational studies.

PURPOSE: We aimed to study the prevalence of human papillomavirus (HPV) in conjunctival intraepithelial neoplasia and carcinoma. Furthermore, we aimed to explore whether geographical differences or different detection modalities are associated with the conflicting information regarding HPV and the development of the disease. METHODS: We searched the MEDLINE, EMBASE and Scopus databases for studies reporting on HPV and conjunctival intraepithelial neoplasia or carcinoma. The pooled prevalence proportions, odds ratio (OR) and corresponding 95% confidence intervals were calculated assuming a random-effects model. Subgroup analyses and meta-regression explored possible sources of heterogeneity. RESULTS: A total of 39 studies were included in the systematic review. The pooled prevalence of HPV in conjunctival intraepithelial neoplasia and carcinoma was 26%, with HPV16, 18, and 33 being the most frequently reported genotypes. Human papillomavirus (HPV) infection was associated with an increased risk of conjunctival intraepithelial neoplasia and carcinoma (OR 8.4, 95% confidence interval (CI) 3.7-19.1); lower in studies from African countries (OR 1.7, 95% CI 0.9-3.5) than other countries (OR 16.1, 95% CI 5.8-44.3), p = 0.013. CONCLUSION: Human papillomavirus infection increases the odds of conjunctival intraepithelial neoplasia and carcinoma by 8.4 compared to healthy conjunctival mucosa or other ocular surface diseases. There seem to be geographical differences regarding HPV in conjunctival intraepithelial neoplasia and carcinoma. HPV16 was the most prevalent genotype, followed by HPV18 and HPV33, meaning that most of the HPV-related conjunctival intraepithelial neoplasia and carcinoma may be prevented by the HPV vaccines that are currently available.

Ocular Surface Disorders in Patients with Human Immunodeficiency Virus (HIV) Infection.

Purpose: To describe ocular surface disorders associated with human immunodeficiency virus (HIV). Methods: Narrative review. Results: Ocular surface neoplastic conditions, such as Kaposi's sarcoma, conjunctival lymphoma and ocular squamous cell carcinoma along with blepharitis, dry eye disease, and vernal keratoconjunctivitis, constitute ocular surface complications in HIV-infected individuals. Conclusion: This review will provide a summary of clinical presentations and treatment options for the most common HIV-related ocular surface diseases, indicating the need for a comprehensive ocular examination including ocular surface in all HIV patients 22.

Extensive bulbar conjunctival Kaposi's sarcoma as initial symptom of human immunodeficiency virus / Sarcoma de Kaposi extenso na conjuntival bulbar como apresentação inicial do vírus da imunodeficiência humana

ABSTRACT Here, we present a case in which extensive bulbar conjunctival Kaposi's sarcoma was the initial presentation of human immunodeficiency virus in a 36-year-old man. The patient had a 3-month history of recurrent self-limited inferior conjunctiva hyperemia in the right eye, and presented with a painless bullous lesion in the right inferior bulbar conjunctiva persisting for 15 days. Surgical incision biopsy was performed at five locations and revealed a pattern compatible with Kaposi's sarcoma. Serologic testing was positive for human immunodeficiency virus; however, the patient had no other symptoms, or knowledge of human immunodeficiency virus infection. This case highlights the need to consider Kaposi's sarcoma as an early presentation of human immunodeficiency virus even if the patient denies infection.

RESUMO Este relato de caso apresenta um sarcoma de Kaposi extenso na conjuntival bulbar como a apresentação inicial do vírus da imunodeficiência humana em um homem de 36 anos de idade. O paciente tinha história de hiperemia na conjuntiva inferior do olho direito há 3 meses, autolimitada e recorrente e de surgimento de uma lesão bolhosa indolor no mesmo local 15 dias antes da sua apresentação. Uma biópsia incisional cirúrgica foi realizada e revelou um padrão compatível com sarcoma de Kaposi. Teste sorológico posterior revelou positividade para o vírus da imunodeficiência humana, no entanto, o paciente não apresentou outros sintomas, sinais ou conhecimento prévio sobre a infecção. Como conclusão deste caso, deve se ressaltar que a suspeita do diagnóstico do sarcoma de Kaposi deve ser levantada ainda que na apresentação inicial do vírus da imunodeficiência humana ou mesmo naqueles ainda sem este diagnóstico.

Extensive bulbar conjunctival Kaposi's sarcoma as initial symptom of human immunodeficiency virus.

Here, we present a case in which extensive bulbar conjunctival Kaposi's sarcoma was the initial presentation of human immunodeficiency virus in a 36-year-old man. The patient had a 3-month history of recurrent self-limited inferior conjunctiva hyperemia in the right eye, and presented with a painless bullous lesion in the right inferior bulbar conjunctiva persisting for 15 days. Surgical incision biopsy was performed at five locations and revealed a pattern compatible with Kaposi's sarcoma. Serologic testing was positive for human immunodeficiency virus; however, the patient had no other symptoms, or knowledge of human immunodeficiency virus infection. This case highlights the need to consider Kaposi's sarcoma as an early presentation of human immunodeficiency virus even if the patient denies infection.

A retrospective review of conjunctival melanoma: Presentation, treatment and evolution. / Revisión retrospectiva del melanoma conjuntival: presentación, tratamiento y evolución.

OBJECTIVE: The purpose of the present study is to describe the clinical characteristics and outcomes of patients diagnosed and treated for conjunctival melanoma in the Ocular Oncology Unit of the University Hospital Clinic of Valladolid. METHODS: A retrospective observational case series study was conducted on patients diagnosed with conjunctival melanoma in the Ocular Oncology Unit of University Hospital Clinic of Valladolid, from January 1992 to December 2017. Demographic information and tumour features were recorded in a Microsoft Access database. RESULTS: Among a total of 462 consecutive patients, the tumour was classified as melanocytic in 252 cases (54.5%), with 27 patients having the pathological diagnosis of conjunctival melanoma. The mean age at diagnosis was 59.2years (16-88), and there were 41% males and 59% females, with a mean follow-up of 6.1±6.8years. As regards the origin of conjunctival melanoma, 16 cases (59%) arose from primary acquired melanosis, 26% from nevus, and 15% developed de novo. The treatment performed was incisional or excisional biopsy in all patients, local adjuvant chemotherapy in 15 cases (56%) and brachytherapy in 5 patients (18%). The median survival was 18years and the probability of survival at 5 and 10years was 89% and 69%, respectively. CONCLUSIONS: Conjunctival melanoma is a rare disease, usually undervalued by the patient as well as being underdiagnosed, leading to insufficient and delayed treatment. Early diagnosis and treatment are essential to prevent recurrences and systemic extension, as well as to preserve vision and life.

Human immunodeficiency virus-associated giant conjunctival Kaposi's sarcoma: complete remission with antiretroviral therapy and systemic chemotherapy. / Sarcoma de Kaposi conjuntival gigante por el virus de inmunodeficiencia humana: remisión total tras terapia antirretroviral y quimioterapia sistémica.

CASE REPORT: A 35-year-old male patient with a large unilateral haemorrhagic conjunctival tumour lesion and another contralateral haemorrhagic conjunctival flat lesion associated with violaceous cutaneous macules on the extremities and angiomatous lesions in the upper gastrointestinal tract as initial clinical manifestation of HIV-related immunodeficiency. Cutaneous, gastric mucosal and conjunctival biopsy was consistent with Kaposi's sarcoma with complete remission after highly active antiretroviral therapy and systemic chemotherapy. CONCLUSION: HIV-related conjunctival Kaposi's sarcoma, even a large one, can have a good response to antiretroviral therapy and systemic chemotherapy without any additional topical eye treatment.

Donor-Derived Conjunctival-Limbal Melanoma After a Keratolimbal Allograft.

PURPOSE: To report a single case of donor-derived conjunctival-limbal melanoma that occurred after a keratolimbal allograft (KLAL). METHODS: Case report and literature review. RESULTS: A 56-year-old white woman with a history of bilateral limbal stem cell deficiency developed a donor-related melanoma after a KLAL. Three months after undergoing an uncomplicated KLAL, the patient presented with hemorrhagic nodules within her conjunctiva and transplanted tissue. Excisional biopsy was performed, and the pathology results revealed melanoma cells. Although the donor of the KLAL had a history of metastatic melanoma, the ocular tissue was in compliance with all eye bank requirements for donation. After discovery of the tumor, the patient's systemic immunosuppression was stopped. Within 1 week, the patient demonstrated a dramatic improvement in the size of the lesion. One month after the initial biopsy, the KLAL tissue was excised, and a pathology report revealed that there were no viable tumor cells on the ocular surface. As the limbal stem cell deficiency recurred, the eye underwent placement of a Boston type 1 keratoprosthesis. CONCLUSIONS: We present a case of conjunctival-limbal melanoma after a KLAL from a donor who had a history of metastatic melanoma. In response to this case, the US eye banking guidelines were amended to include stricter parameters for vascularized ocular tissue transplantation.

Transmission of Donor-Derived Breast Carcinoma as a Recurrent Mass in a Keratolimbal Allograft.

PURPOSE: To report a case of local transmission of invasive lobular carcinoma from a donor to a recipient in a keratolimbal allograft after cessation of systemic immunosuppressive therapy. METHODS: This is a case report including the clinicopathologic findings. Sections of the donor breast tumor and recipient conjunctival lesions were stained with hematoxylin and eosin. Immunohistochemical studies were performed using pancytokeratin, CK7, CK20, CAM 5.2, CD138, TTF1, estrogen receptor, progesterone receptor, GATA-3, GCDFP-15, and mammaglobin. Polymerase chain reaction-based DNA profiling of tumor cells was performed. RESULTS: Histopathologic examination revealed an infiltrate of atypical cells with large hyperchromatic nuclei consistent with carcinoma. Immunohistochemical analysis showed pancytokeratin, CK7, CAM 5.2, GATA-3, and estrogen receptor positivity and progesterone receptor absence, consistent with the previously determined phenotype of the donor's breast carcinoma. Results of polymerase chain reaction analysis were also consistent with the donor's tumor. After reduced dosing of tacrolimus and mycophenolate mofetil, 2 limbal tumors occurred in the recipient. The immunosuppressive treatment had been stopped completely before the appearance of the third lesion. The recipient had no history of malignancy, and she had routine screenings for breast cancer. CONCLUSIONS: We report a case of donor-derived breast carcinoma in a keratolimbal allograft recipient. The grafted tissue harbored donor-derived tumor cells for more than 4 years after surgery even after systemic immunosuppression was discontinued. Although no similar reports of tumor transfer could be found in the literature, this case suggests the need for increased stringency in donor selection and heightened surveillance for such tumor transmission.

Conjunctival Squamous Cell Neoplasia Associated With Ocular Cicatricial Pemphigoid.

The purpose of this study was to describe a possible causal relationship between ocular cicatricial pemphigoid (OCP) and ocular surface squamous neoplasia. Two middle-aged female patients with already diagnosed OCP were studied in regard to the subsequent onset of conjunctival squamous neoplasia. Their clinical histories, ocular examinations, clinical photographs, and results of biopsies and any ancillary immunofluorescent laboratory evaluation studies were carefully reviewed. One patient had a preinvasive squamous dysplasia and the other an invasive squamous cell carcinoma, both in the unequivocal setting of OCP with bilateral conjunctivitis, symblephara, and forniceal foreshortening. The patients had been receiving intensive immunotherapy consisting of some combination of corticosteroids, rituximab, and interferon alpha. Both patients had a positive immunofluorescent study demonstrating immunoreactants at the level of the epithelial basement membrane. Each patient had 2 earlier negative immunofluorescent studies before a third was positive. While rare, there is 1 previous report of an association between OCP and conjunctival squamous neoplasia. The current report provides more data supporting the proposal that this conjunction is more than a random event. Repeat immunofluorescent studies after an initial negative result in a patient with strong clinical signs of OCP are imperative due to the frequency of false negative studies in the context of clinically persuasive disease.

Eyelid Mass in Boston Keratoprosthesis Type 2.

Boston keratoprosthesis type 2 is used to treat severe corneal blindness secondary to cicatricial or autoimmune ocular surface disease. This case report describes an atypical eyelid mass in a 41-year-old woman with Stevens-Johnson syndrome who underwent placement of Boston keratoprosthesis type 2 in the left eye. The postoperative course was complicated by methicillin-sensitive Staphylococcus aureus keratitis and endophthalmitis requiring replacement of the keratoprosthesis. Three months thereafter, the patient presented with a progressively enlarging upper eyelid mass adjacent to the keratoprosthesis optic causing distortion of the eyelid. Excisional biopsy revealed an elongated cystic mass abutting the superior aspect of the optic. Pathologic examination was consistent with a conjunctival cyst with lipogranulomatous reaction. Removal of eyelid margins and conjunctiva, and placement of a full-thickness blepharotomy are standard steps in placement of Boston keratoprosthesis type 2, which can lead to conjunctival cysts and lipogranulomas that present as eyelid masses.

Risk factors for ocular surface squamous neoplasia in Kenya: a case-control study.

OBJECTIVE: To determine modifiable risk factors of ocular surface squamous neoplasia (OSSN) in Kenya using disease-free controls. METHODS: Adults with conjunctival lesions were recruited at four eye care centres in Kenya and underwent excision biopsy. An equal number of controls having surgery for conditions not affecting the conjunctiva and unrelated to ultraviolet light were group-matched to cases by age group, sex and eye care centre. Associations of risk factors with OSSN were evaluated using multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Continuous variables were compared using the t-test or the Wilcoxon-Mann-Whitney U-test depending on their distribution. RESULTS: A total of 131 cases and 131 controls were recruited. About two-thirds of participants were female, and the mean age of cases and controls was 42.1 years and 43.3 years, respectively. Risk factors for OSSN were HIV infection without antiretroviral therapy (ART) use (OR = 48.42; 95% CI: 7.73-303.31) and with ART use (OR = 19.16; 95% CI: 6.60-55.57), longer duration of exposure to the sun in the main occupation (6.9 h/day vs. 4.6 h/day, OR = 1.24; 95% CI: 1.10-1.40) and a history of allergic conjunctivitis (OR = 74.61; 95% CI: 8.08-688.91). Wearing hats was protective (OR = 0.22; 95% CI: 0.07-0.63). CONCLUSION: Measures to prevent and control HIV, reduce sun exposure such as wearing hats and control allergic conjunctivitis are recommended.