Utility of PD-1, PD-L1, and IDO-1 Stains in Ocular Extranodal Marginal Zone Lymphoma (MZL) and Diffuse Large B-cell Lymphoma (DLBCL).

Extranodal marginal zone lymphoma (EMZL) is the most common subtype of ocular lymphomas. Diffuse large B-cell lymphoma (DLBCL) and EMZL with large-cell transformation present diagnostic challenges. Radiotherapy is the standard treatment for ocular lymphomas, but complications and relapse are common. Diagnostic utility in challenging cases, as well as treatment options using immune checkpoint inhibitors, are unclear in ocular lymphomas. We herein investigated the PD-1, PD-L1, and IDO1 staining patterns in 20 cases of ocular lymphomas, including EMZL (n=14), EMZL with increased large cells (n=2), and DLBCL (n=4). PD-1, PD-L1, and IDO1 staining was not detected in lymphoma cells in any cases but was observed within the tumor microenvironment in all cases. Positivity for PD-1, PD-L1, and IDO1 in inflammatory cells was seen either intratumorally or peritumorally. In all 6 cases with significantly more large B cells, the density of PD-1, PD-L1, and IDO1 expression in the tumor microenvironment was higher than that of the remaining 14 cases without large B cells (P-value<0.0001), whereas other clinicopathologic features showed no statistical correlation. Increased expression of PD-1, PD-L1, and IDO1 in the inflammatory milieu in cases with large cells may provide diagnostic utility in small biopsies as well as therapeutic potential.

Clinicopathologic analysis of a case of small cell lung carcinoma metastatic to the retina.

Purpose: Tumor metastases to the retina are a relatively rare occurrence. We report a unique case of retinal metastasis of a systemic malignancy with clinical and histopathologic correlations. Observations: A 62-year-old female with a history of stage IV small cell carcinoma of the lung (SCC, status post chemotherapy and maintenance immunotherapy) presented with hand motions vision and vitreous hemorrhage, status post prior vitrectomy and biopsy that was non-diagnostic. She was found to have unilateral retinal metastatic tumor and underwent a repeat vitrector-assisted biopsy which confirmed the diagnosis. The eye became blind and painful due to recurrent non-clearing vitreous hemorrhage and ghost cell glaucoma and was enucleated. Detailed histopathologic analysis of the globe confirmed small cell carcinoma metastatic to the retina and vitreous cavity and sparing the choroid. Conclusions and importance: This case demonstrates the importance of maintaining a high index of suspicion for metastasis in patients with a known history of malignancy who present with new vitreoretinal lesions.

Next-generation sequencing of a large uveal melanoma with whole genome doubling and a PBRM1 mutation.

Purpose: To report a large uveal melanoma with extra-scleral extension which underwent spontaneous infarction and its unique molecular signature profile. Observations: An 81-year-old female presented with a blind, painful eye. Intraocular pressure was 48 mm Hg. There was a large subconjunctival melanotic mass overlying a choroidal melanoma with anterior extension involving the ciliary body and the iridocorneal angle and iris. Ultrasonography confirmed a dome-shaped anterior cilio-choroidal mass with extra-scleral extension. The patient underwent enucleation and pathologic evaluation confirmed cilio-choroidal melanoma. The posterior half of the tumor involving the ciliary body and the extra-scleral component were spontaneously infarcted and were composed of large melanophages. Next-generation sequencing demonstrated a splice site mutation in PBRM1 and whole-genome doubling in addition to a GNAQ hotspot mutation, chromosome 3 loss and 8q gain. Conclusions and importance: This case of a large, auto-infarcted uveal melanoma demonstrates a PBRM1 mutation and whole-genome doubling.

Prognostic Value of BAP1 and Preferentially Expressed Antigen in Melanoma (PRAME) Immunohistochemistry in Uveal Melanomas.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and despite excellent local control, more than 50% of patients develop and die from metastatic disease. Loss of BAP1 nuclear staining, a surrogate marker of BAP1 mutation, and preferentially expressed antigen in melanoma (PRAME) messenger RNA overexpression, as assessed using qPCR, have previously been shown to correlate with increased metastasis rate in UM. In this study, we demonstrated that UM could be successfully risk-stratified using a combination of BAP1 and PRAME immunohistochemical (IHC) stains. We retrospectively reviewed 318 UM cases with sufficient tissue and performed BAP1 and PRAME IHC to stratify them as BAP1+/PRAME- (group 1, n = 135), BAP1+/PRAME+ (group 2, n = 43), BAP1-/PRAME- (group 3, n = 94), and BAP1-/PRAME+ (group 4, n = 46). Increasing the study risk group on the basis of loss of BAP1 expression and positive PRAME staining was associated with a higher rate of metastasis and disease-specific death and lower metastasis-free survival (MFS) and disease-specific survival (DSS). Among tumors with loss of BAP1 staining, PRAME positivity was associated with shorter MFS (P = .018) and showed a trend toward shorter DSS (P = .061). Among tumors with retained BAP1 staining, PRAME positivity was associated with shorter MFS and DSS (P = .001 and P = .021, respectively). In summary, a combination of BAP1 and PRAME IHC can be used for risk stratification of UMs.

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.

Histologic Changes Following Continuous Wave and Micropulse Transscleral Cyclophotocoagulation: A Randomized Comparative Study.

Purpose: To compare the macroscopic and microscopic histologic changes in eyes treated with micropulse transscleral cyclophotocoagulation (MP-TCP) versus continuous wave transscleral cyclophotocoagulation (CW-TCP). Methods: Twelve halves of globes from three pairs of adult cadaveric eyes were randomly assigned to nontreated control, CW-TCP, single MP-TCP treatment, or double MP-TCP treatments, and then sectioned for histologic analysis. Presence or absence of the following four unique histologic changes was recorded: splitting within the ciliary process epithelium (splitting), separation of the pigmented ciliary process epithelium from the stroma (separation), coagulation of collagen and destruction of ciliary process stroma (coagulation), and full-thickness destruction of ciliary process epithelium (destruction). Results: A total of 498 slides were analyzed, and laser scars in all treated specimens were located in the pars plana. Logistic regression analysis showed that compared with controls, CW-TCP-treated specimens were significantly more likely to experience separation (odds ratio [OR] = 11.1, P = 0.02), coagulation (OR = 24.3, P = 0.002), and destruction (OR = 11.1, P = 0.03). Destruction of the ciliary process epithelium was observed exclusively in CW-TCP-treated sections. No significant differences in histologic features were observed between controls and MP-TCP. Conclusions: MP-TCP does not produce significant histologic changes in cadaveric eyes, whereas CW-TCP treatment does. Translational Relevance: These findings improve understanding of the mechanism of MP-TCP, help explain the increased rates of adverse effects following CW-TCP treatment compared with MP-TCP, and describe effects of MP-TCP at various doses.

Metagenomic Deep Sequencing to Investigate for an Infectious Etiology of Iridocorneal Endothelial Syndrome.

PURPOSE: Iridocorneal endothelial (ICE) syndrome is a group of rare ocular conditions that result from abnormal corneal endothelial cells, leading to secondary glaucoma, iris distortions, and corneal edema. The etiology of ICE is unknown, although it has been associated with viral infections, such as herpes simplex virus. In this study, we sought to identify an infectious etiology for ICE using advanced molecular techniques. METHODS: Metagenomic RNA sequencing (MDS) is a high-throughput sequencing approach that can identify all pathogens in any clinical sample, including RNA viruses. Descemet membrane and aqueous fluid from patients with ICE syndrome were subjected to MDS testing. RESULTS: Samples from 3 patients with ICE were analyzed. MDS was performed on the aqueous fluid of 3 patients and Descemet membrane and endothelial cell tissue from 1 patient. Viral pathogens were not identified in any of the samples. CONCLUSIONS: We were unable to identify a viral etiology in the tissues of patients with the Chandler variant of ICE syndrome, although this study was limited by sample size.

Next-Generation Sequencing of Retinoblastoma Identifies Pathogenic Alterations beyond RB1 Inactivation That Correlate with Aggressive Histopathologic Features.

PURPOSE: To determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma. DESIGN: Cohort study. PARTICIPANTS: Thirty-two children with retinoblastoma. METHODS: We performed targeted NGS using the UCSF500 Cancer Panel (University of California, San Francisco, San Francisco, CA) on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing. MAIN OUTCOME MEASURES: Presence or absence of germline RB1 mutation or deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features. RESULTS: Germline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n = 12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification was identified in 4 tumors (2 with wild-type RB1 and 2 with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been reported previously in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease. CONCLUSIONS: Comprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features.

Loss of ZNF750 in ocular and cutaneous sebaceous carcinoma.

BACKGROUND: Sebaceous carcinoma (SeC) is an uncommon malignancy arising from sebaceous glands of the conjunctiva and skin. Recurrent mutations in the ZNF750 were recently identified in ocular SeC. We assessed whether ZNF750 loss is a specific feature of ocular SeC or a general feature of sebaceous tumors. METHODS: Immunostaining for ZNF750 expression was performed in 54 benign and malignant sebocytic proliferations. Staining for ZNF750 was scored on a three-tier scale: positive (>75%), partially positive (5%-74%), and negative (<5%). RESULTS: ZNF750 expression was negative in 4/11 ocular SeC, and partially positive in 4/11 ocular SeC and 6/13 cutaneous SeC. No extraocular tumors were negative. No loss was found in sebaceous adenoma or sebaceous hyperplasia. In nine previously sequenced ocular SeCs, two lacked detectable somatic mutations in ZNF750, but showed complete loss of staining, indicating non-mutational inactivation of ZNF750. CONCLUSION: We show complete loss of the ZNF750 epidermal differentiation regulator in about half of ocular SeC, highlighting the most common genetic defect in this cancer type. Loss of ZNF750 expression is seen even in tumors without truncating mutations and reduced in many of the remaining ocular and cutaneous SeC. In contrast, no ZNF750 loss was detected in benign sebaceous proliferations.

Metastatic Cutaneous Melanoma Presenting with Choroidal Metastasis Simulating Primary Uveal Melanoma.

PURPOSE: To report a case of metastatic cutaneous melanoma presenting with choroidal metastasis simulating primary uveal melanoma. DESIGN: Case report. METHOD: Presentation of clinical, radiographic, histopathologic, and tumor genetic findings in a patient with cutaneous melanoma with choroidal metastasis. RESULTS: A 50-year-old man with a remote history of stage 1A cutaneous melanoma presented with eye pain, peripheral vision loss, floaters, red eye, and choroidal mass that was originally diagnosed as a primary uveal melanoma at an outside institution; however, subsequent imaging and clinical evaluation demonstrated that this choroidal mass was the first manifestation of widely metastatic cutaneous melanoma (liver, pancreas, lung, bone, brain, and orbit lesions). Histopathologic analysis of the tumor after enucleation was consistent with cutaneous melanoma, and tumor genetic testing was positive for BRAF V600E mutation, confirming the choroidal lesion to be a cutaneous melanoma metastasis rather than a primary choroidal melanoma. CONCLUSIONS: Metastatic cutaneous melanoma to the orbit or globe occurs rarely. Tumor genetic testing may help differentiate metastatic cutaneous melanoma from primary uveal melanoma in cases where the diagnosis is uncertain, and can also inform therapy and prognostic counseling.

Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device.

PURPOSE: We developed a polycaprolactone (PCL) co-delivery implant that achieves zero-order release of 2 ocular hypotensive agents, timolol maleate and brimonidine tartrate. We also demonstrate intraocular pressure (IOP)-lowering effects of the implant for 3 months in vivo. METHODS: Two PCL thin-film compartments were attached to form a V-shaped co-delivery device using film thicknesses of ∼40 and 20 µm for timolol and brimonidine compartments, respectively. In vitro release kinetics were measured in pH- and temperature-controlled fluid chambers. Empty or drug-loaded devices were implanted intracamerally in normotensive rabbits for up to 13 weeks with weekly measurements of IOP. For ocular concentrations, rabbits were euthanized at 4, 8, or 13 weeks, aqueous fluid was collected, and ocular tissues were dissected. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry. RESULTS: In vitro studies show zero-order release kinetics for both timolol (1.75 µg/day) and brimonidine (0.48 µg/day) for up to 60 days. In rabbit eyes, the device achieved an average aqueous fluid concentration of 98.1 ± 68.3 ng/mL for timolol and 5.5 ± 3.6 ng/mL for brimonidine. Over 13 weeks, the drug-loaded co-delivery device resulted in a statistically significant cumulative reduction in IOP compared to untreated eyes (P < 0.05) and empty-device eyes (P < 0.05). CONCLUSIONS: The co-delivery device demonstrated a zero-order release profile in vitro for 2 hypotensive agents over 60 days. In vivo, the device led to significant cumulative IOP reduction of 3.4 ± 1.6 mmHg over 13 weeks. Acceptable ocular tolerance was seen, and systemic drug levels were unmeasurable.

Choroidal Lymphoma Discovered on Ultrasound in a Patient with Suspected Corneal Tumor.

BACKGROUND/AIMS: To report the case of a 77-year-old male with a blind, painful eye, referred for suspected corneal mass, with finding of choroidal B-cell lymphoma on pathology of enucleated globe. METHODS: This is a retrospective case report of a single patient. RESULTS: A 77-year-old male with a longstanding history of poor vision in the left eye was referred for a scarred, vascularized corneal mass. The patient had reported occasional mild ocular discomfort in the left eye and loss of light perception over the last year. Visual acuity was 20/20 in the right eye and no light perception in the left eye. Intraocular pressure was 32 mm Hg in the left eye. Fundoscopic visualization was not possible due to corneal opacity. B-scan ultrasound showed an infiltrative, low-reflective choroidal lesion and inferior retinal detachment. Pathology from the enucleated globe revealed diffuse sheets of CD20+ small B cells replacing the choroid, characteristic of a low-grade small B-cell extranodal marginal zone lymphoma. CONCLUSION: This is an unusual presentation of choroidal lymphoma in an eye with severe corneal opacification and scarring, and underscores the diagnostic value of ultrasonography in examination of eyes without view to the posterior segment.

Cell of origin and mutation pattern define three clinically distinct classes of sebaceous carcinoma.

Sebaceous carcinomas (SeC) are cutaneous malignancies that, in rare cases, metastasize and prove fatal. Here we report whole-exome sequencing on 32 SeC, revealing distinct mutational classes that explain both cancer ontogeny and clinical course. A UV-damage signature predominates in 10/32 samples, while nine show microsatellite instability (MSI) profiles. UV-damage SeC exhibited poorly differentiated, infiltrative histopathology compared to MSI signature SeC (p = 0.003), features previously associated with dissemination. Moreover, UV-damage SeC transcriptomes and anatomic distribution closely resemble those of cutaneous squamous cell carcinomas (SCC), implicating sun-exposed keratinocytes as a cell of origin. Like SCC, this UV-damage subclass harbors a high somatic mutation burden with >50 mutations per Mb, predicting immunotherapeutic response. In contrast, ocular SeC acquires far fewer mutations without a dominant signature, but show frequent truncations in the ZNF750 epidermal differentiation regulator. Our data exemplify how different mutational processes convergently drive histopathologically related but clinically distinct cancers.

Cryptococcal choroiditis in advanced AIDS with clinicopathologic correlation.

PURPOSE: To describe a case of disseminated cryptococcal meningitis with multifocal choroiditis and provide optical coherence tomography (OCT) findings correlated with described histopathology in a patient with advanced acquired immunodeficiency syndrome (AIDS). OBSERVATIONS: The patient was a 54-year-old man with AIDS who presented with dyspnea and headache followed by acute vision loss. OCT demonstrated a lesion with a small area of fluid that was limited by a more prominent and irregular external limiting membrane with underlying nodular choroidal thickening, mild RPE disorganization, and hyperreflectivity of the overlying photoreceptor layer. Patient was found to have disseminated cryptococcal infection and passed away despite aggressive therapy. Autopsy was performed including bilateral enucleation and a Cryptococcus lesion was confirmed on histopathology. CONCLUSION AND IMPORTANCE: This case highlights the clinical, imaging, and histopathologic findings of cryptococcal choroiditis and provides a review of the updated treatment recommendations for disseminated infection in a patient with advanced AIDS. Although currently fundoscopy has proven most useful in directing the diagnostic algorithm in choroiditis in the setting of advanced immunosuppression, OCT may provide insight into the spread of Cryptococcus within the eye.

Local and Regional Spread of Primary Conjunctival Squamous Cell Carcinoma.

Two cases of biopsy-proven conjunctival squamous cell carcinoma (SCC) that developed local and regional spread are described. The cases involved a 65-year-old woman and a 79-year-old man who were initially treated at outside institutions for SCC of the conjunctiva. The patients did not have a history of immune compromise. The female patient presented with direct extension into the lacrimal gland but deferred recommended exenteration. Despite eventual exenteration, she developed metastasis to a neck node 6 months later, which was treated with radiotherapy. The male patient presented with local recurrence and a parotid node metastasis treated with exenteration, parotidectomy, selective neck dissection, and postoperative radiotherapy. Review of the outside pathology of both cases revealed positive tumor margins at the time of original resection. Local control of conjunctival SCC is of critical importance to reduce the risk of orbital extension and regional spread.

Metagenomic deep sequencing of aqueous fluid detects intraocular lymphomas.

INTRODUCTION: Currently, the detection of pathogens or mutations associated with intraocular lymphomas heavily relies on prespecified, directed PCRs. With metagenomic deep sequencing (MDS), an unbiased high-throughput sequencing approach, all pathogens as well as all mutations present in the host's genome can be detected in the same small amount of ocular fluid. METHODS: In this cross-sectional case series, aqueous fluid samples from two patients were submitted to MDS to identify pathogens as well as common and rare cancer mutations. RESULTS: MDS of aqueous fluid from the first patient with vitreal lymphoma revealed the presence of both Epstein-Barr virus (HHV-4/EBV) and human herpes virus 8 (HHV-8) RNA. Aqueous fluid from the second patient with intraocular B-cell lymphoma demonstrated a less common mutation in the MYD88 gene associated with B-cell lymphoma. CONCLUSION: MDS detects pathogens that, in some instances, may drive the development of intraocular lymphomas. Moreover, MDS is able to identify both common and rare mutations associated with lymphomas.

Long-term intraocular pressure reduction with intracameral polycaprolactone glaucoma devices that deliver a novel anti-glaucoma agent.

Long-term treatment of glaucoma, a major leading cause of blindness, is challenging due to poor patient compliance. Therefore, a drug delivery device that can achieve drug release over several months can be highly beneficial for glaucoma management. Here, we evaluate the long-term pharmacokinetics and therapeutic efficacy of polycaprolactone intracameral drug delivery devices in rabbit eyes. Our study showed that a single drug delivery device loaded with a proprietary hypotensive agent, DE-117, reduced intraocular pressure in normotensive rabbits significantly for 23weeks. In addition, we demonstrated that concentration of DE-117 and its hydrolyzed active form (hDE-117) was maintained in the aqueous humor and the target tissue (iris-ciliary body) up to 24weeks. Our proof-of-concept glaucoma implant shows potential as a long-term treatment that circumvents patient compliance barriers compared to current treatment via eye drops.

Uveal Ganglioneuroma due to Germline PTEN Mutation (Cowden Syndrome) Presenting as Unilateral Infantile Glaucoma.

PURPOSE: Uveal ganglioneuroma is a rare tumor that usually occurs in association with neurofibromatosis type 1. Here, we present a rare case of a uveal ganglioneuroma leading to a diagnosis of the tumor predisposition condition Cowden syndrome. PROCEDURES: A 5-year-old girl with unilateral refractory glaucoma secondary to diffuse iris and choroidal thickening developed a blind, painful eye. Enucleation was performed, and histopathology revealed infiltration of the entire uveal tract by neoplastic spindle cells containing admixed ganglion cells diagnostic of uveal ganglioneuroma. Targeted next-generation sequencing of 510 cancer-associated genes was performed on tumor tissue and peripheral blood. RESULTS: A germline nonsense mutation in the PTEN gene was found, accompanied by loss of heterozygosity in the tumor. A diagnosis of Cowden syndrome was made, for which the family sought genetic counseling and initiated the recommended cancer screening. CONCLUSIONS: A novel association is found between uveal ganglioneuroma and Cowden syndrome, emphasizing the value of genetic tissue testing in managing patients with rare ocular tumors.

A novel flexible microfluidic meshwork to reduce fibrosis in glaucoma surgery.

PURPOSE/RELEVANCE: Fibrosis and hence capsule formation around the glaucoma implants are the main reasons for glaucoma implant failure. To address these issues, we designed a microfluidic meshwork and tested its biocompatibility in a rabbit eye model. The amount of fibrosis elicited by the microfluidic meshwork was compared to the amount elicited by the plate of conventional glaucoma drainage device. METHODS: Six eyes from 3 New Zealand albino rabbits were randomized to receive either the novel microfluidic meshwork or a plate of Ahmed glaucoma valve model PF7 (AGV PF7). The flexible microfluidic implant was made from negative photoresist SU-8 by using micro-fabrication techniques. The overall size of the meshwork was 7 mm × 7 mm with a grid period of 100 µm. Both implants were placed in the subtenon space at the supratemporal quadrant in a standard fashion. There was no communication between the implants and the anterior chamber via a tube. All animal eyes were examined for signs of infection and implant erosion on days 1, 3, 7, and 14 and then monthly. Exenterations were performed in which the entire orbital contents were removed at 3 months. Histology slides of the implant and the surrounding tissues were prepared and stained with hematoxylin-eosin. Thickness of the fibrous capsules beneath the implants were measured and compared with paired student's t-test between the two groups. RESULTS: The gross histological sections showed that nearly no capsule formed around the microfluidic meshwork in contrast to the thick capsule formed around the plate of AGV PF7. Thickness of the fibrotic capsules beneath the AGV PF7 plate from the 3 rabbit eyes was 90µm, 82µm, and 95 µm, respectively. The thickness at the bottom of fibrotic capsules around the new microfluidic implant were 1µm, 2µm, and 1µm, respectively. The difference in thickness of capsule between the two groups was significant (P = 0.002). No complications were noticed in the 6 eyes, and both implants were tolerated well by all rabbits. CONCLUSION: The microfluidic meshwork elicited minimal fibrosis and capsule formation after 3-months implantation in a rabbit model. This provides promising evidence to aid in future development of a new glaucoma drainage implant that will elicit minimal scar formation and provide better long-term surgical outcomes.

Primary hepatoid adenocarcinoma of the orbit.

PURPOSE: To report a case of primary hepatoid adenocarcinoma of the orbit. OBSERVATIONS: An adult patient was referred for evaluation of an orbital mass. Histopathology of the orbital biopsy indicated a carcinoma with hepatoid features. Laboratory studies revealed normal liver function tests, elevated serum alpha-fetoprotein, and whole-body positron emission tomography/computed tomography scan showed no evidence of liver involvement or an alternative primary origin. CONCLUSIONS AND IMPORTANCE: To the authors' knowledge, this is the first reported case of primary hepatoid adenocarcinoma of the orbit.