Adjunctive bevacizumab therapy in an equine corneal stromal invasive squamous cell carcinoma with a 53-months follow-up.

A 17-year-old Appaloosa mare was referred for evaluation of presumed refractory keratitis of the left eye. Gross examination revealed ocular discomfort and corneal neovascularization with a nasal focal opacification affecting approximately 40% of the corneal surface. On ophthalmic examination, extensive subepithelial to mid-stromal vascular branching accompanied by a homogeneous white, dense opacification, which affected up to 80% of the total corneal thickness, were apparent. Signs of concurrent uveitis were absent. Deep-stromal lamellar keratectomy with a conjunctival pedicle graft was performed under general anesthesia. Histopathology confirmed a poorly differentiated corneal stromal invasive squamous cell carcinoma (SI-SCC) with neoplastic cell extension to the surgical margins. Postoperatively, 4 topical mitomycin C 0.04% chemotherapy cycles combined with oral firocoxib therapy were initiated. Seven months after surgery, regrowth of the SI-SCC was clinically suspected. A total volume of 1 ml bevacizumab 2.5% was administered in the standing sedated horse via 3 mid-stromal corneal injections. Four weeks later, intrastromal bevacizumab injections (ISBIs) were repeated, however, this time the solution was injected directly into the main corneal vessel branches.Seven weeks after the second ISBIs, the left eye was comfortable and significant remission of corneal vascularization and opacity was recognized. No recurrence has been noted for a follow-up period of more than 53 months.Equine SI-SCC usually has a very poor prognosis for globe maintenance. To the authors' knowledge this is the first report of well-tolerated intrastromal antivascular endothelial growth factor adjunctive therapy with bevazicumab 2.5% and SI-SCC resolution after a multimodal treatment approach.

[Metastasis in the periocular region]. / Metastase in der periokulären Region.

Orbital and periocular metastatic tumors used to be considered very rare; however, with the constant updating of drugs and detection methods for cancer treatment, new chemotherapies and radiation treatments are being used. The life expectancy of cancer patients has become longer and periocular metastases are becoming easier to detect. Our knowledge of this rare disease of metastases also needs to be updated. This article reviews the incidence, symptomatic presentation, clinical features, diagnostic approaches and current treatment of metastatic tumors of the orbit and ocular adnexa in these patients.

Presumed Lacrimal Gland Pleomorphic Adenoma With Extensive Ossification and Necrosis.

Calcification within pleomorphic adenomas of the lacrimal gland is well recognized but uncommon, being seen more readily in lacrimal gland carcinomas. Bony formation, ossification, in pleomorphic adenomas of the lacrimal glands is even rarer. Together with extensive sclerosis, or "coagulative necrosis," ossification and necrosis should alert the clinician to the risk of malignant transformation. However, both can mimic carcinomatous change, leading to misinterpretation of malignancy in an otherwise benign lacrimal gland neoplasm. We present 2 case reports of patients with clinically presumed pleomorphic adenomas of the lacrimal gland whose histopathology demonstrated lacrimal gland ossification and necrosis without features of malignancy or invasive disease.

Exclusive or combined endoscopic approach to tumours of the lower lacrimal pathway: review of the literature.

A literature review was conducted to assess the role of minimally-invasive endoscopic treatments for lacrimal pathway neoplasms. The study involved the analysis of 316 patients with benign or malignant tumours affecting the lacrimal drainage system. Histologically, the analysis revealed a prevalence of squamous cell carcinoma, followed by lymphatic neoplasms and melanomas. In terms of treatment, minimally-invasive endoscopic approaches, such as endoscopic dacryocystorhinostomy, play a predominant role in managing early-stage tumours, rather than merely obtaining samples for histological analysis. For more extensive tumours, which constitute the majority of cases, more aggressive external approaches are required, along with the use of adjuvant radiotherapy and chemotherapy. The lack of universally shared staging systems poses a limitation in standardisation and comparison of results. Treatment of these tumours remains complex due to their rarity and histological heterogeneity. A multidisciplinary approach is mandatory to optimise outcomes.

H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma.

Melanoma represents a public health issue. One of the biggest goals of current research is to develop new therapeutic options for patients affected by this aggressive tumor. We conducted a retrospective study including 105 patients diagnosed with cutaneous and ocular melanoma, with stages varying from pT1a to pT4b and pT4e, respectively, and we performed immunohistochemistry reactions with the new potential prognostic marker, VISTA (V-domain Ig suppressor of T cell activation). We quantified the expression by applying the H-score adapted for VISTA and divided the patients, based on the median value, into groups that presented high, low, and negative expression. Therefore, we obtained 65 cases with positive expression for cutaneous melanoma and 8 cases with positive expression for ocular melanoma. Forty-one cases presented high expression in cutaneous melanoma and three cases presented high expression in ocular melanoma. In cutaneous melanoma, analytic statistics showed that VISTA expression was associated with a high Breslow index, high mitotic count, high Ki67 expression, and advanced clinicopathological stage. The majority of ocular melanoma cases demonstrating a positive reaction were classified as stage pT3, whereas earlier stages showed a negative reaction. Our findings underscore a significant correlation between VISTA expression and key prognostic factors in melanoma. Looking ahead, the prospect of future randomized studies holds promise in corroborating the clinical relevance of our findings. By further elucidating the intricate relationship between VISTA expression and melanoma progression, new treatment strategies could be found, improving patient outcomes in this challenging neoplasm.

[Clinical approach for solid intraocular metastases]. / Klinisches Vorgehen bei soliden intraokulären Metastasen.

BACKGROUND: Intraocular metastases arising from solid tumors are found in approximately 2% of patients with metastatic tumor diseases and are therefore more frequent than originally assumed. They often affect the uvea and are associated with a poor prognosis. Due to the difficult diagnosis and an inconsistent treatment regimen, ophthalmologists have a special responsibility here. OBJECTIVE: This article gives a summary of the various types of intraocular metastases with respect to clinical features, diagnostics, treatment and prognosis as well as recommendations for follow-up care. METHODS: A selective literature search was carried out on the topic of intraocular metastases using PubMed and Google Scholar. RESULTS: Intraocular metastases most frequently affect the uvea, specifically the choroid. In most cases the underlying disease is breast or lung cancer, but other rarer primary tumors have also been reported in the literature. Metastatic lesions can show very different morphological manifestations but can be distinguished based on the corresponding structure of manifestation in the eye and with the aid of targeted staging, thus providing valid information on the type of primary tumor. The treatment is partly experimental and usually depends on the primary tumor and leading symptoms of the patient. A differentiation between a curative or palliative treatment situation must always be made. CONCLUSION: Intraocular metastases are the most frequent intraocular tumor and are usually associated with a poor prognosis. Accurate diagnostics for finding the treatment as well as interdisciplinary collaboration and the presentation of the patient on the tumor board are essential.

[Staging and systemic treatment of ocular and periocular metastases]. / Staging und Systemtherapie bei okulären und periokulären Metastasen.

Metastases of malignant diseases are the most frequent tumors diagnosed in the human eye. They occur in approximately 5-10% of patients with solid tumors during the course of the disease. Their frequency is particularly high in patients with breast and lung cancer. Many highly sensitive periorbital tissues can be affected by the localization of the metastatic lesions and pose a number of clinical challenges. The main goal of the therapy of ocular metastases consists of the control of tumor growth (including the control of other possible manifestations throughout the body), the preservation of the affected eye and the minimization of potential iatrogenic damage to adjacent tissues. Overall, the purpose of this strategy is also to maintain the quality of life and especially the eyes and vision of the patient. Furthermore, pain should be avoided or at least alleviated. Of special importance is the differentiation between a curative or palliative situation. Patients with ocular metastases usually undergo systemic treatment appropriate for the underlying tumor entity, which is often accompanied by concomitant or sequential radiotherapy. In addition to classical chemotherapy, targeted treatment, treatment with monoclonal antibodies and antibody-drug conjugates as well as immunotherapy with checkpoint antibodies are currently available for many cancer types. This review article gives an overview of the currently available treatment options for patients with ocular metastases of solid tumors.

[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.

Intravascular large B-cell lymphoma of the eye: Literature review and new findings.

PURPOSE: Intravascular large B-cell lymphoma (IVLBCL) is an extremely rare, aggressive, multi-system disease that can affect the eye. We describe the ophthalmic presentation, multimodal imaging and treatment response of uveal IVLBCL. METHODS: Review and case report. RESULTS: Twenty-five published cases of IVLBCL involving the eye including our own were identified. Of these, 15 patients (60%) had clinically-detectable intraocular involvement, 6 (24%) had extraocular ophthalmic involvement only and 4 (16%) had subclinical, undiagnosed intraocular involvement that was retrospectively detected on post-mortem ocular histopathology. The male to female ratio was 1.08:1 with a mean presenting age of 65.1 ± 11.7 years (range 38-82 years). The majority of cases had bilateral involvement (21/25 patients, 84%). Extraocular manifestations included diplopia, ptosis and ophthalmoplegia. Intraocular manifestations included serous retinal detachment (13/28, 46%), retinal hemorrhages (9/28, 32%), vascular changes (9/28, 32%), retinal pigment epithelial changes (7/28, 25%), thickened choroid (6/28, 21%), vitritis (5/28, 17%), cotton-wool spots (3/28, 10%), and a subretinal lesion (1/28, 3%). Histopathological diagnosis was most commonly confirmed on post-mortem enucleation (8/25 patients, 32%), skin (6/25 patients, 24%) or brain biopsy (6/25 patients, 24%). CONCLUSION: The presence of intra-retinal hemorrhages, cotton wool spots and/or Roth spots help differentiate IVLBCL from other similarly presenting diseases such as central serous chorioretinopathy and Vogt-Koyanagi-Harada disease. New signs not previously described in IVLBCL include macular bacillary layer detachment and hypo-cyanescent spots on ultra-wide field indocyanine green angiography. The diagnosis is elusive and requires tissue biopsy, but systemic chemotherapy and rituximab can lead to rapid improvement of the eye.

Prognostic Significance of Tumor-Infiltrating Lymphocytes and High-Risk Human Papillomavirus in Ocular Sebaceous Carcinoma: A Comprehensive Analysis.

High-risk human papillomavirus (hrHPV) and tumor-infiltrating lymphocytes (TILs) are known to have prognostic significance in oropharyngeal squamous cell carcinoma. However, their significance in ocular sebaceous carcinoma (OSC) remains unverified because of the rarity of the condition. This study aimed to investigate the association between clinicopathologic features, biomarkers, and hrHPV infection and their potential to predict prognosis in OSC patients. We analyzed the clinicopathologic features of 81 OSC patients from Asan Medical Center between 2000 and 2022. Seventeen biomarkers and hrHPV were examined using immunohistochemistry and DNA in situ hybridization on tissue microarray cores. hrHPV was identified in 31 cases (38.3%). Univariate analysis revealed that hrHPV infection was associated with comedonecrosis (P = .032), high Ki-67 labeling index (≥30%, P = .042), lower expression of E-cadherin (P = .033), and loss of expression of zinc finger protein 750 (P = .023). Multivariate analysis revealed that loss of expression of zinc finger protein 750 (P = .026) remained an independently associated factor for hrHPV. Progression-free survival analysis was performed on 28 patients who were continuously observed for more than 5 years. During a median follow-up duration of 86 months, recurrence or metastasis developed in 14 patients (50%) within the survival cohort, occurring at a median time of 48 months after excision. Univariate analysis indicated that recurrence or metastasis was associated with tumor size (P = .010), high TILs (≥10%; P = .025), lymphovascular invasion (P = 0.043), site of origin (P = .025), and high expression of bcl-2-associated athanogene 3 (P = .039). Multivariate analysis demonstrated that high TILs (P = .017) and site of origin (P = .025) were independent prognostic factors. The prognosis of OSC was hrHPV-independent, and a better prognosis was associated with the site of origin in the order of the gland of Zeis, meibomian gland, and multicentric site, as well as with high TILs.

Cell-Free DNA Extraction of Vitreous and Aqueous Humor Specimens for Diagnosis and Monitoring of Vitreoretinal Lymphoma.

Vitreoretinal lymphoma (VRL) represents an aggressive lymphoma, often categorized as primary central nervous system diffuse large B-cell lymphoma. To diagnose VRL, specimens such as vitreous humor and, more recently, aqueous humor are collected. Diagnostic testing for VRL on these specimens includes cytology, flow cytometry, and molecular testing. However, both cytopathology and flow cytometry, along with molecular testing using cellular DNA, necessitate intact whole cells. The challenge lies in the fact that vitreous and aqueous humor typically have low cellularity, and many cells get destroyed during collection, storage, and processing. Moreover, these specimens pose additional difficulties for molecular testing due to the high viscosity of vitreous humor and the low volume of both vitreous and aqueous humor. This study proposes a method for extracting cell-free DNA from vitreous and aqueous specimens. This approach complements the extraction of cellular DNA or allows the cellular component of these specimens to be utilized for other diagnostic methods, including cytology and flow cytometry.

Neoadjuvant Intra-arterial Cytoreductive Chemotherapy Improves Outcomes in Lacrimal Gland Adenoid Cystic Carcinoma.

BACKGROUND: Lacrimal gland adenoid cystic carcinoma (LGACC) has historically been associated with a poor prognosis even with localized disease, with a survival of 56% at 5 years. In 1988, we treated the first patient with neoadjuvant intra-arterial cytoreductive chemotherapy (IACC). Since then, we have used this protocol as the standard approach. We aim to analyze the outcomes of patients with LGACC treated with the protocol and compare them to a population-based cohort to assess if IACC can improve survival. METHODS: We prospectively assessed all non-metastatic patients with LGACC treated with IACC at a single institution between 1988 and 2021. For a comparison group, we identified all non-metastatic patients with LGACC treated with excision from the Surveillance, Epidemiology, and End Results (SEER) registry. We calculated disease-specific survival using the Kaplan-Meier and Cox proportional-hazards modeling methods. RESULTS: Thirty-five non-metastatic patients with LGACC treated with IACC were identified at a single institution, and 64 patients with non-metastatic LGACC treated with excision were identified in the SEER database. The 5- and 10-year disease-specific survival rates for patients treated with IACC were 84% (95%CI 71-97) and 76% (95%CI 60-92), respectively. While the 5- and 10-year disease-specific survival rates for the population-based cohort were 72% (95%CI 62-82) and 46% (95%CI 32-60). The survival analysis favored IACC, with a 60% lower risk of death (HR: 0.4; 95%CI 0.2-0.9). CONCLUSION: IACC improves disease-specific survival in comparison to a population-based cohort treated with excision. Additional patients treated with IACC at multiple institutions are required to provide further external validity.

Intraocular schwannoma: case series of 28 patients and literature review.

PURPOSE: Intraocular schwannoma is a rare tumour, which is often misdiagnosed. We presented the demographics and clinical characteristics of patients with intraocular schwannoma. METHODS: Retrospective case series were collected between May 2005 and July 2021 in Beijing Tongren Hospital. RESULTS: A total of 28 patients were diagnosed with intraocular schwannoma on histopathological examination of surgical specimen. The median age was 39 years (range: 12-64). Fourteen patients were female and 14 were male. Among the all subjects, 21/28 patients (75.0%) presented as visual loss, and 3/28 patients (10.7%) had visual field loss. Intraocular schwannoma presented as nonpigmented mass in the ciliary body in 12/28 cases (42.9%), in the choroid in 9/28 cases (32.1%), and in ciliochoroid in 7/28 cases (25.0%). Intraocular schwannoma was often clinically misdiagnosed as uveal melanoma, which occurred in 16/28 patients (57.1%). Tumour excision with pars plana vitrectomy was performed for all included patients. Endoresection with lens removal was performed for tumours in the choroid, while transscleral resection was performed for tumours located in ciliary body or ciliochoroid. Increased light transmission was detected in 12/28 cases (42.9%). In the consecutive follow-up (median: 73 months, range: 7-193 months), no cases of recurrence or metastatic disease were detected. CONCLUSIONS: Intraocular schwannoma is a rare benign tumour. It usually presents as nonpigmented mass, which can easily be misdiagnosed as nonpigmented uveal melanoma.