Sympathetic Ophthalmia in Patients with Enucleation or Evisceration: Pathology Laboratory and IRIS® Registry Experience.

Introduction: Sympathetic ophthalmia (SO) is a rare bilateral granulomatous panuveitis that can follow surgical or nonsurgical ocular trauma in one eye. Because its diagnosis requires clinical-pathologic correlation, the true incidence of SO is unknown, and there is a need to understand the recent trends in risk factors and frequency of this condition. Methods: Pathology records of all enucleated or eviscerated (ENEV) eyes at three pathology laboratories were reviewed. Data collected included patient demographics, procedure indication, pathology diagnosis, and clinical history of trauma and uveitis. IRIS® Registry (Intelligent Research in Sight) was searched for all patients with SO, acquired absence of eye (AAE), and/or ENEV. Data obtained included patient demographics, ocular procedures, and preoperative diagnoses within 30 days of AAE/ENEV. Results: In the pathology laboratory setting, the incidence of SO over a 36-year period in patients who underwent ENEV was 0.2% (20/9,092); the 5-year incidence ranged from 0.0 to 0.3%. Among the 20 eyes with SO, the inciting event was surgical trauma in 50% (10/20), nonsurgical trauma in 45% (9/20), and missing/undetermined in 5% (1/20). SO was suspected preoperatively in 7/20 (35%) patients. Clinical concern for SO and ruptured globe were indications for ENEV in 50/9,092 (0.5%) and 872/9,092 (10%) patients, respectively. In the IRIS Registry, 0.7% (199/27,830) of patients with AAE/ENEV had diagnosis of SO. The frequency of SO between 2015 and 2020 was 0.01% (7,371/62,318,249); of these 7,371 cases, 199 (3%) had AAE/ENEV. In 25,975 patients with available data, injury and SO were listed as diagnoses less than 30 days prior to AAE/ENEV in 909 (4%) and 63 (0.2%) cases, respectively. Conclusion: The frequency of SO in recent decades has been low. Most cases of SO are not managed with eye removal. In histopathology-confirmed SO, surgical trauma is as frequent as nonsurgical trauma as an inciting etiology of disease.

Acute lymphocytic leukemia masquerading as acute retinal necrosis.

PURPOSE: To report a case of B-cell acute lymphocytic leukemia (ALL) relapse presenting as acute retinal necrosis. OBSERVATIONS: An 11-year old boy with history of B-cell ALL undergoing maintenance therapy presented with a three-month history of intermittent blurry vision and pain in the right eye when a routine lumbar puncture indicated an elevated lymphoblast-predominant white blood cell count. Bone marrow biopsy revealed 42% lymphoblasts, confirming ALL relapse. Ophthalmic imaging demonstrated a hyperemic optic disc, retinal whitening, perivascular sheathing, retinal hemorrhages, and retinal detachment in the right eye. Vitreous fluid biopsy revealed presence of rare atypical lymphoblasts. Chemotherapy, orbital radiation, and systemic prednisone resulted in improvement of visual acuity and retinal hemorrhages, and resolution of retinal detachment. CONCLUSIONS AND IMPORTANCE: We have described the clinical features, treatment, and response in a case of B-cell ALL relapse with presenting signs of acute retinal necrosis. The uncommon finding in B-cell ALL highlights the possibility of intraocular involvement and the importance of routine ophthalmologic evaluation in leukemia remission.

Characterizing the impact of 2D and 3D culture conditions on the therapeutic effects of human mesenchymal stem cell secretome on corneal wound healing in vitro and ex vivo.

The therapeutic effects of secreted factors (secretome) produced by bone marrow-derived human mesenchymal stem cells (MSCs) were evaluated as a function of their growth in 2D culture conditions and on 3D electrospun fiber scaffolds. Electrospun fiber scaffolds composed of polycaprolactone and gelatin were fabricated to provide a 3D microenvironment for MSCs, and their mechanical properties were optimized to be similar to corneal tissue. The secretome produced by the MSCs cultured on 3D fiber matrices versus 2D culture dishes were analyzed using a Luminex immunoassay, and the secretome of MSCs cultured on the 3D versus 2D substrates showed substantial compositional differences. Concentrations of factors such as HGF and ICAM-1 were increased over 5 times in 3D cultures compared to 2D cultures. In vitro proliferation and scratch-based wound healing assays were performed to compare the effects of the secretome on corneal fibroblast cells (CFCs) when delivered synchronously from co-cultured MSCs through a trans-well co-culture system versus asynchronously after harvesting the factors separately and adding them to the media. Cell viability of CFCs was sustained for 6 days when co-cultured with MSCs seeded on the fibers but decreased with time under other conditions. Scratch assays showed 95% closure at 48 h when CFCs were co-cultured with MSCs seeded on fibers, while the control group only exhibited 50% closure at 48 h. Electrospun fibers seeded with MSCs were then applied to a rabbit corneal organ culture system, and MSCs seeded on fibers promoted faster epithelialization and less scarring. Corneas were fixed and stained for alpha smooth muscle actin (α-SMA), and then analyzed by confocal microscopy. Immunostaining showed that expression of α-SMA was lower in corneas treated with MSCs seeded on fibers, suggesting suppression of myofibroblastic transformation. MSCs cultured on electrospun fibers facilitate wound healing in CFCs and on explanted corneas through differential secretome profiles compared to MSCs cultured on 2D substrates. Future work is merited to further understand the nature and basis of these differences and their effects in animal models. STATEMENT OF SIGNIFICANCE: Previous studies have shown that the secretome of bone marrow-derived mesenchymal stem cells (MSC) is promotes corneal wound healing by facilitating improved wound closure rates and reduction of scarring and neovascularization. The present research is significant because it provides evidence for the modulation of the secretome as a function of the MSC culture environment. This leads to differential expression of therapeutic factors secreted, which can impact corneal epithelial and stromal healing after severe injury. In addition, this article shows that co-continuous delivery of the MSC secretome improves cell migration and proliferation over aliquoted delivery, and that MSCs grown on three-dimensional electrospun fiber constructs may provide a favorable microenvironment for cultured MSCs and as a carrier to deliver their secreted factors to the ocular surface.

A Convergence of Ophthalmic and Life-threatening Emergencies: Acute Angle Closure Glaucoma and Subarachnoid Hemorrhage.

PURPOSE: To report a unique case of acute angle closure glaucoma in the setting of a subarachnoid hemorrhage due to a ruptured cerebral aneurysm. MATERIALS AND METHODS: Observational case report and review of the literature. RESULTS: A 75-year-old woman presented with blurry vision, nausea, vomiting, and left eye pain. She was found to have a complete third nerve palsy, with ptosis, exotropia, hypotropia, and a fixed mydriasis with resultant acute angle closure glaucoma. Pilocarpine was initiated, and neuroimaging revealed a subarachnoid hemorrhage from a ruptured posterior communicating artery aneurysm. The aneurysm was successfully coiled, and outpatient laser iridotomies were subsequently performed. Only 4 prior cases of acute angle closure glaucoma in the setting of a third nerve palsy have been reported in the literature. To our knowledge, this case is the first report of angle closure glaucoma in the setting of a subarachnoid hemorrhage. CONCLUSIONS: This case of a complete third nerve palsy in the setting of a subarachnoid hemorrhage leading to acute angle closure highlights the importance of ruling out this life-threatening diagnosis when neurological signs of increased intracranial pressure and cranial nerve palsies are present.

A novel platform for isotype-specific testing of autoantibodies.

The objective of this study was to test if a novel platform could be used for isotype-specific autoantibody testing in humans. Further, we evaluated if testing with this novel platform enables earlier detection of insulin autoantibodies in individuals that have first-degree relatives with type-1 diabetes than currently used approaches. Longitudinal serum samples from participants were collected before and after they converted to become positive for insulin autoantibodies by the current standardly used assays. Using a novel plasmonic gold chip platform, we tested these samples for IgM isotype-specific autoantibodies. Serial serum samples from individuals without diabetes were also tested as a comparison control cohort. Our results demonstrate proof-of-concept that a plasmonic gold chip can specifically detect the IgM insulin autoantibody. Five out of the six individuals that converted to being positive for insulin autoantibodies by standard testing had significant IgM autoantibodies on the plasmonic chip platform. The plasmonic chip platform detected IgM autoantibodies earlier than standard testing by up to 4 years. Our results indicate that the plasmonic gold platform can specifically detect the IgM isotype autoantibodies and suggest that combining isotype-specific testing with currently used approaches enables earlier detection of insulin autoantibodies in individuals that have first-degree relatives with type 1 diabetes.