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1.
J Ophthalmic Vis Res ; 18(1): 51-59, 2023.
Article in English | MEDLINE | ID: mdl-36937188

ABSTRACT

Purpose: Adenosine signaling modulates ocular inflammatory processes, and its antagonism mitigates neovascularization in both newborns and preclinical models of ocular neovascularization including age-related macular degeneration (AMD). The adenosine receptor expression patterns have not been well characterized in the human retina and choroid. Methods: Here we examined the expression of adenosine receptor subtypes within the retina and choroid of human donor eyes with and without AMD. Antibodies specifically targeting adenosine receptor subtypes A1, A2A, A2B, and A3 were used to assess their expression patterns. Quantitative real-time PCR analysis was used to confirm gene expression of these receptors within the normal human retina and choroid. Results: We found that all four receptor subtypes were expressed in several layers of the retina, and within the retinal pigment epithelium and choroid. The expression of A1 receptors was more prominent in the inner and outer plexiform layers, where microglia normally reside, and supported by RNA expression in the retina. A2A and A2B showed similar expression patterns with prominent expression in the vasculature and retinal pigment epithelium. No dramatic differences in expression of these receptors were observed in eyes from patients with dry or wet AMD compared to control, with the exception A3 receptors. Eyes with dry AMD lost expression of A3 in the photoreceptor outer segments compared with eyes from control or wet AMD. Conclusion: The ocular presence of adenosine receptors is consistent with their proposed role in modulation of inflammation in both the retina and choroid, and their potential targeting for AMD treatment.

2.
Blood Cancer J ; 11(5): 103, 2021 05 26.
Article in English | MEDLINE | ID: mdl-34039952

ABSTRACT

Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody-drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit-risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Corneal Diseases/chemically induced , Corneal Diseases/therapy , Multiple Myeloma/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Cornea/drug effects , Cornea/pathology , Corneal Diseases/pathology , Disease Management , Humans , Neoplasm Recurrence, Local/drug therapy , Patient Care Team
4.
Ophthalmic Plast Reconstr Surg ; 35(5): e115-e116, 2019.
Article in English | MEDLINE | ID: mdl-31503170

ABSTRACT

A 7-year-old healthy girl presented for an evaluation of a left vascular scleral mass. The lesion appeared spontaneously with no history of trauma, coagulopathy, or topical medication use. It was nontender, enlarging, and did not extend intraocularly. Her OS vision was 20/20, and the remainder of her eye examination was normal. Evaluation of the ocular mass included B-scan ultrasound, ultrasound biomicroscopy, anterior segment optical coherence tomography (OCT), and orbital MRI. The anterior segment OCT demonstrated vessels within the mass with no defined capsule. The orbital MRI confirmed a lesion isolated to the scleral layers of the globe, with low blood flow. The patient had a partial response to oral propranolol. Because the lesion vessels began to extend into her corneal endothelium, there was a concern for malignancy. A biopsy confirmed a benign intrascleral capillary hemangioma. Discontinuation of the propranolol demonstrated stability of the lesion 6 months later.


Subject(s)
Eye Neoplasms/pathology , Hemangioma, Capillary/pathology , Sclera/pathology , Child , Female , Humans
6.
J Pediatr Ophthalmol Strabismus ; 54: e88-e90, 2017 Nov 17.
Article in English | MEDLINE | ID: mdl-29156063

ABSTRACT

The authors report the case of a 2-year-old girl who presented with an acute ruptured globe secondary to penetration by the casing of a .22 caliber cartridge that was ignited by a car cigarette lighter. Although penetrating injuries are a common mechanism of ocular trauma, open globe induced by cartridge casing represents an unusual and preventable cause. [J Pediatr Ophthalmol Strabismus. 2017;54:e88-e90.].


Subject(s)
Accidents, Home , Eye Enucleation/methods , Eye Injuries, Penetrating/diagnosis , Visual Acuity , Child, Preschool , Eye Injuries, Penetrating/physiopathology , Eye Injuries, Penetrating/surgery , Female , Humans , Rupture , Tomography, X-Ray Computed , Trauma Severity Indices
7.
J AAPOS ; 21(2): 159-160, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28219740

ABSTRACT

We report the case of a premature infant with end-organ failure who developed high-risk retinopathy of prematurity (ROP) bilaterally and was treated with intravitreal bevacizumab (IVB) injection therapy with regression noted on follow-up clinical examination. The infant died 3 weeks after IVB injection therapy. Histopathological analysis was conducted on bilateral globes and revealed persistent preretinal vessels.


Subject(s)
Bevacizumab/administration & dosage , Infant, Premature , Retina/pathology , Retinopathy of Prematurity/pathology , Angiogenesis Inhibitors/administration & dosage , Cell Proliferation , Endothelium, Vascular/pathology , Fatal Outcome , Humans , Infant , Intravitreal Injections , Laser Coagulation , Male , Multiple Organ Failure/complications , Retinopathy of Prematurity/complications , Retinopathy of Prematurity/therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors
8.
Ophthalmology ; 122(9): 1765-70, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26130328

ABSTRACT

PURPOSE: The purpose of this study was to determine in which species and under what conditions lens tumors occur. DESIGN: A review of databases of available human and veterinary ocular pathologic material and the previously reported literature. PARTICIPANTS: Approximately 18 000 patients who had ocular surgical specimens submitted and studied at the University of Wisconsin School of Medicine and Public Health between 1920 and 2014 and 45 000 ocular veterinary cases from the Comparative Ocular Pathology Laboratory of Wisconsin between 1983 and 2014. METHODS: Material in 2 major archived collections at the University of Wisconsin medical and veterinary schools were studied for occurrence of lens tumors. Tumor was defined as a new growth of tissue characterized by progressive, uncontrolled proliferation of cells. In addition, cases presented at 3 major eye pathologic societies (Verhoeff-Zimmerman Ophthalmic Pathology Society, Eastern Ophthalmic Pathology Society, and The Armed Forces Institute of Pathology Ophthalmic Alumni Society) from 1975 through 2014 were reviewed. Finally, a careful search of the literature was carried out. Approval from the institutional review board to carry out this study was obtained. MAIN OUTCOME MEASURES: The presence of tumors of the lens. RESULTS: The database search and literature review failed to find an example of a lens tumor in humans. In contrast, examples of naturally occurring lens tumors were found in cats, dogs, rabbits, and birds. In the veterinary school database, 4.5% of feline intraocular and adnexal neoplasms (234/5153) were designated as feline ocular posttraumatic sarcoma, a tumor previously demonstrated to be of lens epithelial origin. Similar tumors were seen in rabbit eyes, a bird, and in a dog. All 4 species with lens tumors had a history of either ocular trauma or protracted uveitis. The literature search also revealed cases where lens tumors were induced in zebrafish, rainbow trout, hamsters, and mice by carcinogenic agents (methylcholanthrene, thioacetamide), oncogenic viruses (SV40, HPV-16), and genetic manipulation. CONCLUSIONS: Our results suggest that lens tumors do not occur in humans. In contrast, after lens capsule rupture, a lens tumor can occur in other species. We hypothesize that a genetic mechanism exists that prevents lens tumors in humans.


Subject(s)
Eye Neoplasms/pathology , Eye Neoplasms/veterinary , Lens Diseases/pathology , Lens Diseases/veterinary , Animals , Cats , Cricetinae , Databases, Factual , Dogs , Female , Human papillomavirus 16/pathogenicity , Humans , Male , Mice , Mice, Transgenic , Oncorhynchus mykiss , Rabbits , Simian virus 40/pathogenicity , Species Specificity , Spheniscidae , Zebrafish
12.
Arch Ophthalmol ; 130(1): 33-8, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22232473

ABSTRACT

OBJECTIVE: To investigate a correlation between the severity of histologic changes of the Descemet membrane in patients with Fuchs endothelial dystrophy and the best-corrected visual acuity (VA) after Descemet membrane-stripping automated endothelial keratoplasty (DSAEK). METHODS: In a retrospective study design, we created a histologic grading system based on common characteristics observed histologically among 92 DSAEK specimens sent to the University of Wisconsin Eye Pathology Laboratory with a clinical diagnosis of Fuchs dystrophy from 3 separate corneal surgeons. Cases were graded as mild, moderate, or severe on the basis of guttae dispersion, presence of a laminated Descemet membrane, presence of embedded guttae, and density of guttae. Regression models were built to study the relationship among preoperative VA, histologic findings, and best-corrected VA 6 months and 1 and 2 years after DSAEK. RESULTS: No correlation was found between the severity of histologic changes of Descemet membrane and preoperative VA. However, a correlation was noted between the preoperative and final VA. Cases with a laminated Descemet membrane but no embedded guttae (n = 8) appeared to be less responsive to DSAEK. Otherwise, the severity of histologic changes of Descemet membrane observed in patients with Fuchs corneal dystrophy after DSAEK did not show a statistically significant correlation with final VA. CONCLUSIONS: Our analysis fails to show an inverse relationship between the severity of histologic changes of the Descemet membrane and the best-corrected VA of at least 20/40 after DSAEK for Fuchs endothelial dystrophy. However, in a subset of patients with Fuchs dystrophy who develop a laminated Descemet membrane without embedded guttae, the visual recovery after DSAEK is less than expected. The laminated architecture of Descemet membrane without embedded guttae may facilitate separation between the membrane layers and, thus, incomplete removal of the recipient's Descemet membrane during DSAEK, which may then limit the postoperative visual outcome.


Subject(s)
Descemet Stripping Endothelial Keratoplasty , Fuchs' Endothelial Dystrophy/surgery , Visual Acuity/physiology , Corneal Stroma/physiopathology , Fuchs' Endothelial Dystrophy/classification , Fuchs' Endothelial Dystrophy/physiopathology , Humans , Postoperative Period , Retrospective Studies
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