Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages

In the inflamed cornea, there is a parallel outgrowth of blood and lymphatic vessels into the normally avascular cornea. We tested whether adaptive and/or innate immune cells were actively involved in the genesis of new lymphatic vessels. Our results indicate that innate immune cells (CD11b+ macrophages, but not CD11c+ dendritic cells) physically contributed to lymphangiogenesis under pathological conditions and that bone marrow-derived CD11b+ macrophages expressed lymphatic endothelial markers such as LYVE-1 and Prox-1 under inflamed conditions in the corneal stromata of mice. Furthermore, blood vascular endothelial cells that expressed the Tie2 promoter did not contribute to newly formed lymphatic vessels under inflamed conditions. Our in vitro experiments demonstrated that CD11b+ macrophages alone were capable of forming tube-like structures that expressed markers of lymphatic endothelium such as LYVE-1 and podoplanin. The novel finding that CD11b+ macrophages are critical for the development of inflammation-dependent lymphangiogenesis in the eye suggests a new mechanism of lymphangiogenesis.     

Oculocerebral non-Hodgkin's lymphoma with uveal involvement: development of an epibulbar tumor after vitrectomy

Primary ocular lymphoma is the ocular manifestation of primary oculocerebral non-Hodgkin's lymphoma. We describe a 79-year-old woman with a 7-year history of bilateral uveitis and subsequent central nervous system lymphomas. Repeated diagnostic vitrectomy during the following 5 years failed to demonstrate intraocular lymphoma cells. Within 9 months after the second vitrectomy, an epibulbar tumor developed in the limbal region of the left eye at the site of the sclerotomy. The eye, blind and painful due to secondary angle-closure glaucoma, was enucleated. Histopathologically, the globe showed a diffuse large B-cell non-Hodgkin's lymphoma extending from the ciliary body outward through the sclerotomy. We conclude that, following vitrectomy, a primary ocular lymphoma may extend through the sclerotomy lesion and present as an epibulbar tumor. Uveal involvement may occur in oculocerebral non-Hodgkin's lymphoma.     

Synopsis of various electrophysiological tests in early glaucoma diagnosis--temporal and spatiotemporal contrast sensitivity, light- and color-contrast pattern-reversal electroretinogram, blue-yellow VEP

BACKGROUND: Of the three glaucoma-defining criteria intraocular pressure, optic-nerve damage, and visual field damage, the latter is a late symptom. Therefore, in order to improve an early sensory diagnosis, new tests are necessary. It is the aim of the present paper to test new sensory methods, to rank them in an order of sensitivity, and to base them on possible pathophysiological mechanisms. PATIENTS AND METHODS: The tests were carried out in subjects of the Erlangen Glaucoma registry: Normals, patients with ocular hypertension, and patients with open-angle glaucoma without or with field defects. The tests are designed to preferentially probe the function of different groups of ganglion cells. Psychophysical methods: Temporal contrast sensitivity in a ganzfeld as "Erlangen flicker test" and spatio-temporal contrast sensitivity to test Magno-cell function. Electrophysiological methods: Pattern-reversal electroretinogram with a luminance-contrast pattern to test Magno-cell function, color-contrast pattern electroretinogram for Parvo-cell function, and blue-on-yellow visual evoked potential to test the "blue-sensitive" pathway. RESULTS: The most sensitive test is the temp.CS, it is significantly reduced in OHT (p < 0.01). The spatio-temp.CS is reduced in perimetric stages (p < 0.01). The BY-VEP is altered in the preperimetric stage (p < 0.01), the PR-ERG in perimetric stages (p < 0.01). The CC-ERG is reduced in even later stages. These results are in agreement with the hypothesis that tests selective for non-redundant neurons are of early diagnostic value. Multivariate analyses increase the early diagnostic value when different functions are tested in combination. CONCLUSIONS: When a particular test is taylored to the the special needs of certain groups of ganglion cells sensory defects can be observed before the occurrence of optic-nerve damage (OHT). The most sensitive psychophysical test is the "Erlangen flicker test" which is a screening test selective for M cells. The most sensitive electrophysiological test is the BY-VEP testing the blue-sensitive ganglion cells.     

Reduced recovery of temporal contrast sensitivity after flicker stress in patients with glaucoma

PURPOSE: To compare recovery of temporal contrast sensitivity after flicker stress between control subjects and patients with glaucoma. METHODS: Forty-three patients with primary open-angle glaucoma and secondary open-angle or normal-tension glaucoma of the Erlangen Glaucoma Registry and 30 healthy control subjects had their temporal contrast sensitivity measured at 37 Hz and their recovery time determined after monocular exposure to 30 seconds of 58% contrast full-field flicker. Recovery time of temporal contrast sensitivity was measured as the time interval from cessation of flicker until twice the threshold value was reached. RESULTS: Patients with glaucoma had a significant reduction in temporal contrast sensitivity (P < 0.001). Recovery time was also significantly longer in patients with glaucoma (23.8 +/- 24.1 seconds) than in control subjects (7.6 +/- 2.6 seconds; P < 0.001). There was a significant positive correlation between recovery time and mean visual field defect (0.5; P < 0.001) and a significant negative correlation between recovery time and neuroretinal rim area of the optic disc (0.32; P = 0.04). CONCLUSIONS: Recovery of temporal contrast sensitivity after flicker stress is impaired in some patients with glaucoma. This might be the result of functional impairment of the inner retina, outer retina, or both in glaucoma.     

Lymphatic vessels in vascularized human corneas: immunohistochemical investigation using LYVE-1 and podoplanin

PURPOSE: To determine whether lymphatic vessels exist in vascularized human corneas, by using immunohistochemistry with novel markers for lymphatic endothelium. METHODS: Human corneas exhibiting neovascularization secondary to keratitis, transplant rejection, trauma, and limbal insufficiency (n = 21) were assessed for lymphatic vessel content by conventional transmission electron microscopy and by immunostaining and immunoelectron microscopy with antibodies specific for the lymphatic endothelial markers, lymphatic vessel endothelial hyaluronan receptor (LYVE-1) and the 38-kDa integral membrane glycoprotein podoplanin. In addition, corneas were stained for the lymphangiogenic growth factor VEGF-C, and its receptor VEGFR3 by immunohistochemistry and in situ RNA hybridization, respectively. RESULTS: Thin-walled, erythrocyte-free vessels staining with lymphatic markers (LYVE-1 and podoplanin) were found to constitute 8% of all vessels, to be more common in the early course of neovascularization, to be always associated with blood vessels and stromal inflammatory cells, and to correlate significantly with the degree of corneal hemangiogenesis (r = 0.6; P = 0.005). VEGF-C, VEGFR3, podoplanin, and LYVE-1 colocalized on the endothelial lining of lymphatic vessels. With immunogold labeling, LYVE-1 and podoplanin antigen were found on endothelial cells lining vessels with ultrastructural features of lymph vessels. CONCLUSIONS: Immunohistochemistry with novel lymph-endothelium markers and ultrastructural analyses indicate the existence of lymphatic vessels in vascularized human corneas. Human corneal lymphangiogenesis appears to be correlated with the degree of corneal hemangiogenesis and may at least partially be mediated by VEGF-C and its receptor VEGFR3.     

Bilateral nevus of the caruncle

BACKGROUND: Pathologic processes of the caruncle are relatively rare with a predominance of papillomas, pyogenic granulomas and nevi. PATIENT: A 22 year old Caucasian male patient presented with bilateral hyperpigmentations of the caruncle. They had first been observed at an age of seven and showed slight progression in size and colour with time. Examination revealed hyperpigmentation with clear pseudocystic spaces. The tarsal or bulbar conjunctiva was not involved. An excision of both processes was performed. HISTOLOGY: Light microscopy revealed nests of nevus cells with melanin granules and round basophilic nuclei as well as gland ducts and sebaceous glands, beneath and within the multilayered keratinizing and nonkeratinizing squamous epithelium. The sections revealed a bilateral melanocytic compound nevus of the caruncle. DISCUSSION: To our knowledge, there is no report on bilateral nevi of the caruncle among the Caucasian population. The possibility of a common precursor cell during the embryologic development causing the bilaterality is discussed.