Local resection via partial lamellar sclerouvectomy for ciliary body tumors - a case series.

BACKGROUND: Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. METHODS: Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. RESULTS: Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00-10.00) and the mean tumor thickness was 3.50 mm (range: 2.00-5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. CONCLUSIONS: Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

Pigmented medulloepithelioma of the optic nerve: A challenging diagnostic entity.

Because of its rarity, the diagnosis of optic nerve medulloepithelioma poses a real diagnostic challenge. Medulloepithelioma is a congenital tumor that derives from the primitive medullary epithelium present in the neural tube and the optic vesicle. Its classical location is the ciliary body. Cases of retinal or optic nerve locations have been rarely reported in the literature. Only 11 cases have been published in the English literature. Herein, we report the case of a 2-year-old boy who underwent enucleation of the right eye for a presumed diagnosis of right-eye retinoblastoma, based on the presence of leukocoria on ophthalmological examination. Pathological examination showed an optic nerve medulloepithelioma. A review of the literature is also discussed in our work.

Intraocular medulloepithelioma: an unusual and challenging entity in paediatric population.

Intraocular medulloepithelioma is a rare, congenital tumour of the non-pigmented ciliary epithelium. It most frequently arises from the ciliary body but can also have its origin from the retina, iris and optic nerve. The age when lesion first appears is typically around 2-10 years. Nearly 50-60% of patients having this lesion may also have secondary features such as cataract and neovascular glaucoma. Those with extrascleral medulloepithelioma are at risk for metastasis. Systemic correlation of the tumour with pleuropulmonary blastoma/DICER1 gene is reported in the literature. Here, we report a case of a 15 years old boy with one year history of right eye proptosis and painful red right eye along with decreased vision for one week. He was assessed and operated for cataract elsewhere three years back. The ophthalmology team managed him for endophthalmitis with intravenous antibiotics, followed by 2 sessions of cryotherapy and finally an enucleation of right eye was performed due to severe pain and no vision in the involved eye. His left eye, general physical examination and systemic evaluation were normal. Histopathology revealed the diagnosis of 'malignant teratoid medulloepithelioma'. Therefore, evaluation of systemic associations for DICER1 gene mutations was performed by the oncology team. For high risk feature of scleral invasion on histopathology, he was treated with chemotherapy. Since the tumour is of rare occurrence; an international expert team with vast research experience in PPB/DICER1 associated tumours was also contacted. He was registered in International PPB/DICER1 registry where a detailed central radiology and pathology review was performed. Genetic counseling and surveillance plan was also suggested by the international registry.

[Adenocarcinoma of nonpigmented ciliary body epithelium (clinical cases)]. / Adenokartsinoma iz bespigmentnogo epiteliya tsiliarnogo tela (klinicheskie nablyudeniya).

The article presents two clinical cases of adenocarcinoma of nonpigmented epithelium of the ciliary body, which is a very rare malignant tumor of the organ of vision with distinctive features. Surgical treatment is necessary to verify this tumor and assess the degree of its aggressiveness in terms of the prognosis of the disease, with subsequent pathomorphological and immunohistochemical studies. The article also discusses the epidemiological aspects, morphological features, clinical manifestations of this pathological condition, as well as possible treatment options and features of follow-up monitoring of this group of patients.

Tumor Profiles of Late Presentation Uveal Ring Melanoma With Novel Characteristics - A Case Series.

Purpose: The purpose of this study was to investigate the clinical features, tumor characteristics, including histopathology and cytogenetic analysis, and management of patients with uveal ring melanoma in New Zealand. Methods: A retrospective review was conducted on all uveal melanoma cases treated in a single national oncology center in New Zealand. The study period was from January 1, 2013 to December 31, 2022 (10 years). Written consent was obtained from all patients included in this case series. Results: Uveal ring melanoma of ciliary body origin (n = 4) comprised 0.7% of all uveal melanomas (n = 571). Ethnicity distribution was three patients of New Zealand European ancestry and one patient of Chinese/Pasifika ancestry. Three patients (75%) were symptomatic at presentation (spontaneous hyphema, glaucoma, and cataract), whereas one was asymptomatic but subsequently developed painful refractory glaucoma. All eyes underwent enucleation. Three eyes had primary iris biopsies with subsequent enucleation for refractory glaucoma and pain and one eye underwent primary enucleation. All cases demonstrated malignant tumor characteristics including diffuse 270 to 360-degree ciliary body ring growth pattern, epithelioid-cell type and presence of either BAP-1 expression loss or gain of MYC gene. Two cases (50%) developed distant organ metastasis - liver, parotid gland, and breast. Of those, one patient was deceased at the time of follow-up whereas one had completed treatment for metastases. Conclusions: Uveal ring melanoma is a rare tumor that is highly invasive and malignant. When detected, prompt definitive treatment should be advocated, and patient counselling should be given regarding the high risk of developing a painful, blind eye with increased risk of metastasis in the absence of treatment.

Ocular metastasis from renal malignancies - A comprehensive review.

The most common cause of intraocular mass is metastasis from other tumors. Renal malignancies, though rare, have a substantial number of cases with ocular metastasis, few of which were misdiagnosed. Many a times renal malignancies present with ocular manifestations before the primary diagnosis. Here in this article, we comprehensively reviewed 106 cases of ocular metastasis from renal malignancies published till date to the best of our knowledge. The eye is a rare site for distant metastasis because of the lack of a lymphatic system. The most common ocular structures to get involved in distant metastasis are the uveal tract, i.e., choroid, iris, and ciliary body. The most common renal tumor which metastasizes to eyes is renal cell carcinoma (RCC). RCC accounts for less than 2% of all ophthalmic metastases. Out of total 106 cases, the type of renal malignancy was known in 95 cases only, of which 92 had RCC, 1 Wilm's tumor, 1 rhabdoid tumor, and 1 medullary carcinoma. The age ranged widely from 2 weeks old to 81 years old. The male to female ratio was 3.4:1. In total, 67.4% of cases had a previous history of RCC, while the rest 32.6% primarily presented with ophthalmic manifestations first. Treatment modalities included enucleation of the eye, debulking surgery followed by radiotherapy and/or chemotherapy and/or immunotherapy.

Morroniside Ameliorates Endotoxin-Induced Uveitis by Regulating the M1/M2 Polarization Balance of Macrophages.

Background: Inflammation is closely associated with the pathogenesis of various ocular diseases. Uveitis is a condition characterized by the inflammation of the uvea and ocular tissues that causes extreme pain, decreases visual acuity, and may eventually lead to blindness. The pharmacological functions of morroniside, isolated from Cornus officinalis, are multifarious. Morroniside exerts various therapeutic effects, e.g., it ameliorates inflammation. However, the specific anti-inflammatory effect of morroniside on lipopolysaccharide-induced uveitis has not been reported widely. In this study, we investigated the anti-inflammatory effect of morroniside on uveitis in mice. Methods: An endotoxin-induced uveitis (EIU) mouse model was constructed and treated with morroniside. The inflammatory response was observed using slit lamp microscopy, and histopathological changes were observed by hematoxylin-eosin staining. The cell count in the aqueous humor was measured using a hemocytometer. The concentrations of TNF-α, IL-6, and IL-1ß in the ciliary body and retina were measured using ELISA kits. The expression of iNOS and Arg-1 in the ciliary body and retina was measured by immunofluorescence costaining, and western blotting was performed to measure the protein expression of JAK2, p-JAK2, STAT3, and p-STAT3 in the ciliary body and retina. Results: Morroniside effectively ameliorated the inflammatory response in EIU mice. Furthermore, morroniside significantly reduced the concentrations of IL-1ß, IL-6, and TNF-α in the ciliary body and retina. Morroniside treatment significantly reduced the expression of iNOS in the ciliary body and retinal tissues. It also significantly inhibited p-JAK2 and p-STAT3 expression and promoted Arg-1 expression. In addition, morroniside boosted the effect of JAK inhibitors on the above indices. Conclusions: Collectively, these findings suggest that morroniside may protect against LPS-induced inflammation in uveitis by promoting M2 polarization through the inhibition of the JAK/STAT pathway.

Multipurpose ultrasonographic characteristics of primary uveal MALT lymphoma.

PURPOSE: To investigate the ultrasonographic features in patients with primary uveal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Medical records of 12 patients (13 eyes) diagnosed with primary uveal MALT lymphoma between September 2014 and September 2021 were retrospectively reviewed. Ultrasonography, B-scan ultrasonography, color Doppler flow imaging, and ultrasound biomicroscopy findings were retrieved from the medical records. RESULTS: Mean age of the included patients was 59.4 ± 8.6 years. Typical ultrasonographic features of the choroidal infiltrates were flat, diffuse, and thickened, with low and homogenous internal reflectivity and with rich arterial blood flow from posterior ciliary arterioles. The mean thickness of the choroidal infiltrates was 1.34 ± 0.68 mm (n = 13). Most of the affected eyes had posterior episcleral extensions, with a mean thickness of 1.66 ± 1.21 mm (n = 12). Typical crescent-like posterior episcleral extensions were detected in nine eyes (69.2%). In six eyes, the blood flow from the choroidal infiltrates communicated with the episcleral extensions. In the ciliary body, the mean thickness of the infiltrates was 1.08 ± 0.43 mm (n = 9), and seven eyes (77.8%) had 360° ring-like infiltrations. The initial best-corrected visual acuity (BCVA) was significantly correlated with the final BCVA after treatment (p < 0.001). CONCLUSION: Multipurpose ultrasonographic imaging revealed the unique characteristics of the primary uveal MALT lymphoma and is helpful in the diagnosis of this rare disease.

IgG4-related ophthalmic disease masquerading as ciliary body tumors and scleritis in both eyes: a case report.

BACKGROUND: To report a rare case of IgG4-related ophthalmic disease (IgG4-ROD) manifesting as intraocular masses and scleritis in both eyes in a 61-year-old male and to investigate the changes in multimodal imaging features of the lesion sites and helper T-cell type 1 (Th 1)/Th 2/Th 17 cytokine levels in the aqueous humor. CASE PRESENTATION: A patient with IgG4-ROD seemingly manifested with an intraocular tumor in the left eye and sequentially, with an inflammatory mass in the ciliary body and scleritis in the right eye. The patient complained of vision loss of 6 months duration in the left eye at his first visit. With a preliminary diagnosis of an intraocular tumor, enucleation of the left eyeball and histopathological examination were performed. Approximately 3 months later, the patient started to experience headache, eye pain, and declining vision in the right eye. Ophthalmic imaging revealed a ciliary mass and scleritis. Th 1/Th 2/Th 17 cytokine levels and multimodal imaging findings were analyzed before and after corticosteroid treatment. Histopathological examination and immunohistochemistry (IHC) of the enucleated left eye demonstrated lymphoplasmacytic infiltration with an IgG4+/IgG+ cell ratio of approximately 40%, pointing to the diagnosis of probable IgG4-ROD. Long-term treatment with corticosteroids led to significant improvement in the signs and symptoms of the left eye. Th 1/Th 2/Th 17 cytokine profile monitoring of the aqueous humor and multimodal imaging of the right eye showed gradual regression of the mass and attenuation of ocular inflammation during treatment. CONCLUSIONS: Patients with an atypical presentation of IgG4-ROD, such as intraocular masses and scleritis, are likely to experience a significant delay in diagnosis. This case demonstrates the significance of IgG4-ROD in the differential diagnosis of intraocular tumors and ocular inflammation. IgG4-RD is a newly diagnosed disease with multi-organ involvement and little is known about its pathogenesis, particularly in the eye. The present case will open new challenges in the clinico-pathological diagnosis and research of this disease. Combined investigations of multimodal imaging and cytokine level detection of intraocular fluid provide a new and effective way to monitor disease progression.

Large ciliary body melanocytoma with pseudocysts: a case report.

BACKGROUND: To describe the correlation between standardized A-scan echography and histopathology in a ciliary body melanocytoma. CASE PRESENTATION: We present a case of a large ciliary body melanocytoma with significant growth, vision loss, and elevated intraocular pressure that was diagnosed clinically as a melanoma, but the standardized A-scan findings correlated to the histopathological description of a melanocytoma with multiple pseudocysts. CONCLUSIONS: The reflectivity of this melanocytoma by standardized A-scan was consistent with multiple pseudocysts on pathological evaluation. This echographic pattern guided the differential diagnosis. Standardized A-scan is an important diagnostic tool in the differentiation of ciliary body melanocytomas from melanomas.

Cytogenetic Abnormalities for Predicting the Risk of Metastases in Choroidal and Ciliary Body Melanoma.

Purpose: Choroidal melanoma (CM) and ciliary body melanoma (CBM) are the two most common subtypes of uveal melanoma. Starting from the observation that CBM tends to have a higher metastatic potential than CM, we hypothesized that specific cytogenetic abnormalities could be associated with tumor location - reflecting distinct genetic signatures that would drive the risk of distant spread. Methods: Chromosomal alterations were investigated by molecular cytogenetic techniques in 217 and 97 patients with CM and CBM, respectively. Cox proportional hazards regression analysis was used to identify the independent predictors of distant metastasis. Results: Patients with CBM had larger tumor sizes (P < 0.001), higher disease stages (P < 0.001), and more frequently showed distant metastasis (P = 0.002) than those with CM. On analyzing the entire study cohort, we found that specific chromosomal alterations - including chromosome 8p loss (P < 0.001), 1p loss (P < 0.001), and monosomy 3 (P < 0.005) - were independent predictors of distant metastasis. Based on a decision-tree learning algorithm, we identified three specific subgroups of patients with uveal melanoma at high risk of distant spread. Monosomy 3 occurred significantly more frequently in patients with T3 CBM tumors. Conclusions: Specific cytogenetic abnormalities - including chromosome 8p loss, 1p loss, and monosomy 3 - are independent risk factors for distant metastasis in uveal melanoma. Larger tumor size at presentation and monosomy 3 contribute to a higher metastatic risk in patients with CBM.

Metastatic tumours to the eye. Review of metastasis to the iris, ciliary body, choroid, retina, optic disc, vitreous, and/or lens capsule.

Metastasis to the eye can involve the choroid (90%), ciliary body (2%), iris (8%), and retina, optic disc, vitreous, and/or lens capsule (<1-4%). The mean number of uveal metastasis per eye (1.7), mean tumour base (11.6 mm) and thickness (3.2 mm), tumour colour (86% yellow), and presence of subretinal fluid (72%), are all clinical features suggestive of the diagnosis. Imaging with ultrasonography demonstrates an echodense mass (80%) and optical coherence tomography shows a "lumpy bumpy" choroidal surface (64%), both important diagnostic features. Uveal metastases typically emanate from primary cancer of the breast (37%), lung (27%), kidney (4%), gastrointestinal tract (4%), cutaneous melanoma (2%), lung carcinoid (2%), prostate (2%), thyroid (1%), pancreas (1%), and other sites (3%). Occasionally, fine needle aspiration biopsy is employed if the primary site is not known. In 16% of cases, the primary site remains unknown. Rarely, metastases affect the retina, vitreous, and lens capsule, most often originating from cutaneous melanoma and in patients previously treated with checkpoint inhibitor therapy. Kaplan-Meier analysis in a series of 1111 patients with uveal metastasis revealed 32% survival at 3 years and 24% at 5 years. Patients with uveal metastasis from carcinoid tumour showed most favourable survival at 5-years (92%), whereas pancreatic and kidney cancer demonstrated least favourable survival (0%). The 5-year survival was better for females (versus (vs.) males) (31% vs. 21%) and older adults (vs. children) (40% vs. 0%). In this review, we examine several large-cohort publications on the topic of ocular metastasis.

Proton beam radiotherapy for choroidal and ciliary body melanoma in the UK-national audit of referral patterns of 1084 cases.

INTRODUCTION: Proton beam therapy has been utilised for the treatment of uveal melanoma in the UK for over 30 years, undertaken under a single centre. In the UK, all ocular tumours are treated at one of four centres. We aimed to understand the variation in referral patterns to the UK proton service, capturing all uveal melanoma patients treated with this modality. METHODS: Retrospective analysis of data regarding all patients treated at the Clatterbridge Proton service between January 2004 and December 2014. RESULTS: A total of 1084 patients with uveal melanoma were treated. The mean age was 57 years (range 9-90 years), basal diameter of 11.5 mm (range 2.0-23.4 mm) and tumour thickness of 3.9 mm (range 0.1-15.4 mm). The majority were TNM stage I (39%) or II (36%). The distance to the optic nerve varied from 0 to 24.5 mm with 148 (14%) of patients having ciliary body involvement. There were variations in the phenotypic characteristic of the tumours treated with protons from different centres, with London referring predominantly small tumours at the posterior pole, Glasgow referring large tumours often at the ciliary body and Liverpool sending a mix of these groups. DISCUSSION: In the UK, common indications for the use of proton treatment in uveal melanoma include small tumours in the posterior pole poorly accessible for plaque treatment (adjacent to the disc), tumours at the posterior pole affecting the fovea and large anterior tumours traditionally too large for brachytherapy. This is the first UK-wide audit enabling the capture of all patients treated at the single proton centre.

Pineal Parenchymal Tumor of Intermediate Differentiation and DICER1 Syndrome: A Case Report.

DICER1 syndrome is a rare inherited tumor predisposition syndrome associated with an increased risk for several malignant and benign tumors. We present a patient with pineal parenchymal tumor of intermediate differentiation who was found to have a germline pathogenic variant in DICER1 gene. Pineoblastoma is a known DICER1-related tumor; however, the association between pineal parenchymal tumor of intermediate differentiation and DICER1 mutation is rare with only 1 recent large molecular study that has reported this association. This report adds to the evolving tumor spectrum of DICER1 and highlights the importance of molecular evaluation of pediatric brain tumors, for both therapeutic decisions and long-term surveillance.

Determinants of Long-Term Survival in Metastatic Choroidal and Ciliary Body Melanoma.

PURPOSE: To build and validate a prognostic model that predicts long-term overall survival (OS) in metastatic choroidal and ciliary body melanoma (CCBM) to facilitate patient counseling and planning, reporting, and interpreting clinical trials. DESIGN: Retrospective cohort study with validation. METHODS: We analyzed predictors of intermediate (IMT; 25-<42 months) and long-term (LT; ≥42 months) OS in a Finnish nationwide cohort of 330 patients with metastatic CCBM. Short-term (<25 months), IMT, and LT survival were compared with pairwise and ordinal logistic regression. A single-center cohort of 259 patients from Italy was used for validation. Models were compared with a deviance test. RESULTS: Median OS was 12 and 17 months in the building and validation datasets, respectively; 40 (12%) and 31 (9%) compared with 44 (17%) and 32 (12%) patients were IMT and LT survivors, respectively. Alkaline phosphatase or lactate dehydrogenase level never exceeded 2 times the upper normal limit (UNL) in either LT cohort. Conditional to both being ≤2 times the UNL, distant metastasis-free interval (DMFI) >42 months (odds ratio [OR] 4.09-4.64; P < .001) paired with age <60 years (OR 3.23; P = .002), having no symptoms (OR 4.19; P = .005), and the largest diameter of the largest metastasis <30 mm (Tumor, Node, Metastasis stage M1a; OR 3.05; P = .001) independently predicted higher odds of surviving longer (IMT or LT) without model preference. These results were confirmed in the validation dataset. CONCLUSIONS: Alkaline phosphatase or lactate dehydrogenase >2 times the UNL essentially precluded LT survival. The most robust predictor otherwise was DMFI >42 months, followed by age <60 years, absence of symptoms, and Tumor, Node, Metastasis stage M1a.

Choroidal melanoma tumor profile and treatment pattern for newly diagnosed patients at a reference public hospital in Sao Paulo, Brazil.

BACKGROUND: Choroid, ciliary body, and iris melanomas are often grouped as uveal melanoma, the most common intraocular primary malignancy. The purpose of the current study was to analyze the tumor profile of newly diagnosed cases of choroidal melanoma at a reference center in Sao Paulo, Brazil, and to investigate the frequency of eyes treated by enucleation that could have been treated with brachytherapy if available in the service. METHODS: Medical records of patients referred to our service with initial diagnostic hypothesis of choroidal melanoma from July 2014 to June 2020 were analysed on demographics, diagnosis confirmation, tumor measurement by ultrasonography and established treatment. Data were evaluated on clinical and demographic characteristics as age, sex, affected eye, ultrasound parameters, and treatment management of patients with clinically diagnosed choroidal melanoma. Among the patients submitted to enucleation, we investigated how many could have been selected to receive brachytherapy. RESULTS: From the 102 patients referred with the choroidal melanoma diagnosis hypothesis, 70 (68.62%) were confirmed. Mean measurements from the tumors in millimetres were: 9.19 ± 3.69 at height and 12.97 ± 3.09 by 13.30 ± 3.30 at basal. A total of 48 cases (68.57%) were enucleated, 8 (11.43%) were treated by brachytherapy in a different service, and 14 patients (20.00%) returned for enucleation at their original referral center. Out of the 48 patients enucleated, 26 (54.17%) could have been selected to brachytherapy treatment. CONCLUSIONS: The results indicate a late diagnosis of choroidal melanoma cases referred to our service. Most enucleated cases could have been treated with brachytherapy if it was broadly available at the national public health insurance. Further public health political efforts should focus on early diagnosis and better quality of life post-treatment for oncologic patients.

Malignant teratoid intraocular ciliary body medulloepithelioma in a 5-year-old male with corresponding somatic copy number alteration profile of aqueous humor cell-free DNA.

BACKGROUND: Intraocular, ciliary body, medulloepithelioma (CBME) is a rare tumor of the nonpigmented ciliary body epithelium, typically presenting in childhood. We describe a case of CBME. MATERIALS AND METHODS: Ocular examination and imaging guided diagnostic and treatment decisions. Aqueous humor (AH) liquid biopsy was collected from the affected eye at eventual enucleation. Whole genome sequencing (WGS) was employed to determine somatic copy number alterations (SCNA) in AH cell-free DNA (cfDNA). Tumor sample was analyzed using various assays to evaluate for oncogenic mutations and SCNAs. Histopathology determined diagnosis. RESULTS: A 5-year-old male with glaucoma and cataract in the left eye (OS) experienced worsening left eye pain and redness. There was no light perception OS and the eye was hypotonus. Anterior segment exam showed complete cataract and rubeosis iridis. Ocular B-scan ultrasound OS revealed an intraocular lesion with calcifications and retinal detachment. Orbital MRI suggested left globe hypercellularity. An infiltrative lesion involving the ciliary body was seen in the left eye on examination under anesthesia. Left eye enucleation was performed in the setting of pain, blindness, and tumor, with anterior chamber paracentesis for AH liquid biopsy collection. SCNA profile of AH cfDNA demonstrated loss of copy of chromosomes 4, 6, and 9. Tumor was negative for clinically significant mutations or SCNAs. Histopathology diagnosed malignant teratoid CBME. CONCLUSIONS: We present a case of CBME and include the unique SCNA profile of AH cfDNA from the enucleated eye. This case suggests utility of AH liquid biopsy in distinguishing between differential diagnoses for intraocular mass lesions.

A single-cell transcriptomic atlas of the human ciliary body.

The ciliary body critically contributes to the ocular physiology with multiple responsibilities in the production of aqueous humor, vision accommodation and intraocular immunity. Comparatively little work, however, has revealed the single-cell molecular taxonomy of the human ciliary body required for studying these functionalities. In this study, we report a comprehensive atlas of the cellular and molecular components of human ciliary body as well as their interactions using single-cell RNA sequencing (scRNAseq). Cluster analysis of the transcriptome of 14,563 individual ciliary cells from the eyes of 3 human donors identified 14 distinct cell types, including the ciliary epithelium, smooth muscle, vascular endothelial cell, immune cell and other stromal cell populations. Cell-type discriminative gene markers were also revealed. Unique gene expression patterns essential for ciliary epithelium-mediated aqueous humor inflow and ciliary smooth muscle contractility were identified. Importantly, we discovered the transitional states that probably contribute to the transition of ciliary macrophage into retina microglia and verified no lymphatics in the ciliary body. Moreover, the utilization of CellPhoneDB allowed us to systemically infer cell-cell interactions among diverse ciliary cells including those that potentially participate in the pathogenesis of glaucoma and uveitis. Altogether, these new findings provide insights into the regulation of intraocular pressure, accommodation reflex and immune homeostasis under physiological and pathological conditions.

Evidence of lymphatics in the rat eye retina.

BACKGROUND: The lymphatic structure of the eye is still under debate. It is mainly assumed that the retina is primarily drained by prelymphatics and not by lymphatics per se. We aimed to identify lymphatics in the rat retina. METHODS: Eyes from ten Wistar rats were paraffin-embedded and the lymphatic marker podoplanin (D2-40) was investigated. RESULTS: We identified in the rat retina a blunt-end network of lymphatic endothelial vessels. It consisted of circumferential vessels within the outer and, respectively, inner plexiform layers, connected by radial dichotomous vessels. Moreover, D2-40 expression was found within the choroid, ciliary body, and extraocular muscles. CONCLUSIONS: This in situ evidence is strongly supported by the recent in vitro demonstration of the expression of lymphatic markers in retinal endothelial cells. Further studies of comparative histology should use specific lymphatic markers to test whether other species besides rats have proper retinal lymphatics.

Iris and Ciliary Body Melanocytomas Are Defined by Solitary GNAQ Mutation Without Additional Oncogenic Alterations.

OBJECTIVE: To analyze the genetic features of melanocytomas and melanomas of the anterior uvea and assess the value of molecular testing for diagnosis and prognostication. DESIGN: Retrospective case-control study. SUBJECTS: Patients with melanocytoma (n = 16) and melanoma (n = 19) of the anterior uvea. METHODS: Targeted next-generation sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue from anterior uveal melanocytic tumors and correlated with clinicopathologic features. MAIN OUTCOME MEASURES: Presence or absence of accompanying oncogenic alterations beyond GNAQ/GNA11 and their association with histologic features and local recurrence. RESULTS: Hotspot missense mutations in GNAQ/GNA11 were identified in 91% (32/35) of all cases. None of the melanocytomas with or without atypia demonstrated chromosomal imbalances or additional oncogenic variants beyond GNAQ mutation, and none recurred over a median follow-up of 36 months. Additional alterations identified in a subset of melanomas include mutations in BAP1 (n = 3), EIF1AX (n = 4), SRSF2 (n = 1), PTEN (n = 1), and EP300 (n = 1); monosomy 3p (n = 6); trisomy 6p (n = 3); trisomy 8q (n = 2); and an ultraviolet mutational signature (n = 5). Local recurrences were limited to melanomas, all of which demonstrated oncogenic alterations in addition to GNAQ/GNA11 (n = 5). A single melanoma harboring GNAQ and BAP1 mutations and monosomy 3 was the only tumor that metastasized. CONCLUSIONS: In this study, anterior segment uveal melanocytomas did not display oncogenic alterations beyond GNAQ/GNA11. Therefore, they are genetically similar to uveal nevi rather than uveal melanoma based on their molecular features known from the literature. Molecular testing can be performed on borderline cases to aid risk stratification and clinical management decisions.