[Show abstract][Hide abstract] ABSTRACT: Orbital neoplasms with associated bone erosions and intracranial extension are generally considered suspicious for malignancies. Here, we describe the clinical and radiological findings, as well as the surgical management of two extraordinary cases, in which such bony perforations with subsequent intracranial tumor growth resulted from benign angiomatous orbital neoplasms. Two female patients, 69 years old (case 1) and 51 years old (case 2), had both developed visual symptoms (visual field restrictions and/or visual acuity loss) over several months. Computed tomography revealed an orbital tumor of the anterosuperior orbit with painless swelling of the medial upper eyelid of the right eye in case 1, and a posterior intraconal tumor close to the orbital apex of the left eye in case 2, respectively. In both cases, the tumor was associated with a perforation of the orbital roof connecting the orbit with the anterior cranial fossa. An interdisciplinary ophthalmologic and neurosurgical approach allowed for complete tumor removal, in both patients with no signs for local recurrence during the subsequent follow-up of 15 and 18 months, respectively, as well as for a satisfactory visual rehabilitation.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Conjunctival melanoma (CM) is an ocular surface tumor that can lead to fatal metastases. Patients developing, tumor-associated lymphangiogenesis have a significantly increased risk of metastatic disease, because tumor spread primarily occurs via lymphatic vessels to the draining lymph node. Here, we describe a novel immune-competent mouse model of CM that displays tumor-associated lymphangiogenesis with development of metastatic tumors.
C57BL/6N mice received C57BL/6N-derived dermal melanoma cells (hepatocyte growth factor [HGF] cyclin dependent kinase-4 [Cdk4]+) or B16F10 via subconjunctival injection. A clinical score quantified primary tumor growth and metastases were identified by macroscopic examination of the draining lymph nodes, lung, and spleen. Confirmation of tumors and metastases was achieved by immunohistochemical staining for markers of pigmented cells (tyrosinase related protein-2 [TRP2]) and S-100, and of cell proliferation (Ki67). The intra- and peritumoral CD31+ blood and lymphatic vessel endothelium hyaluronan receptor-1 (LYVE-1)+ lymphatic vessels were quantified immunohistochemically.
All mice rapidly developed aggressive TRP2+, S100+, and Ki67+ CM. Metastatic tumors were found in the lymph node (9%) and lung (6%) of HGF-Cdk4R24C-treated mice and in the spleen (8%) and lung (17%) of B16F10-treated mice. The amount of peri- and intratumoral blood vessels was significantly increased compared with lymphatic vessels.
This CM model in immune-competent animals offers new possibilities to study the pathobiology of tumor growth, invasion, and mechanisms of metastatic tumor spread, and provides a robust model to explore new immune-based and antilymphangiogenic treatment modalities of this malignancy.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Malignant melanomas of the ocular surface (conjunctival melanoma [CM]) and within the eye (uveal melanoma [UM]) show different types of metastatic behavior. While CM has a propensity to spread first to regional lymph nodes, UM metastasizes almost exclusively via the hematogenic route to the liver. We investigated whether these different metastatic patterns might be attributable to differential hem- and lymphangiogenic characteristics of CM and UM cells.
Human CM (CM2005.1, CRMM1, CRMM2) and UM (Mel270, Mel290, OM431) cell lines were analyzed for VEGF-A, -C, and -D expression by RT-PCR and ELISA. The influence of CM- or UM-conditioned medium on blood (BEC) and lymphatic (LEC) endothelial cell proliferation and migration was measured using 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl-tetrazolium bromide (MTT) and scratch assays, respectively.
Vascular endothelial growth factor-A, -C and -D mRNA, and VEGF-A and -D protein were expressed by all CM and UM cell lines, while VEGF-C protein was only expressed by UM cell lines. The CM- and UM-conditioned medium did neither differentially affect BEC (P = 0.86) and LEC (P = 0.90) proliferation, nor BEC (P = 0.56) and LEC (P = 0.90) migration.
Conjunctival melanoma cell lines did not show a higher prolymphangiogenic potential, and UM cell lines did not show a higher prohemangiogenic potential. Accordingly, other mechanisms within the tumor microenvironment might account for the diverging metastatic patterns of conjunctival versus uveal melanomas.
[Show abstract][Hide abstract] ABSTRACT: A 3-year-old boy presented with acute corneal hydrops on the left eye and spontaneous corneal rupture on the right eye. A diagnosis of brittle cornea syndrome was confirmed by molecular analysis. A novel mutation, the homozygous variant c.17T>G, p.V6G, was found in the gene for PR-domain-containing protein 5 (PRDM5) in exon 1. Brittle cornea syndrome is a rare connective tissue disease with typical ocular, auditory, musculoskeletal, and cutaneous disorders. Almost all patients suffer from declined vision due to corneal scarring, thinning, and rupture. The most common ophthalmologic findings include keratoconus, progressive central corneal thinning, high myopia, irregular astigmatism, retinal detachment, and high risk for spontaneous corneal or scleral rupture. In addition to describing the case with a novel mutation here we review the current literature on brittle cornea syndrome pathogenesis, clinical findings, and therapy.
[Show abstract][Hide abstract] ABSTRACT: In patients with small-fiber neuropathy (SFN), noninvasive diagnostic tests that allow accurate monitoring of disease progression are urgently needed. The aim of this study was to assess corneal trigeminal small sensory nerves and immune cells by in vivo corneal confocal microscopy (CCM) in SFN.
In this prospective single-center study, 14 patients with histologically confirmed SFN were analyzed. CCM parameters [corneal nerve fiber density (NFD); the total number of nerves, main trunks, and branches; nerve tortuosity; and dendritic cell density] were compared with 14 age-matched healthy controls and correlated with clinical symptoms, disease course, and histopathological findings.
Corneal NFD (15,489.3 ± 5927.6 μm/mm vs. 22,687.1 ± 4328.7 μm/mm; P = 0.001) and the total number of nerves (10.4 ± 4.6/frame vs. 18.5 ± 4.8/frame; P < 0.0001) were significantly reduced in patients with SFN. In contrast, nerve tortuosity was significantly increased (2.2 ± 0.3 vs. 1.7 ± 0.5; P = 0.02). Corneal NFD did not correlate with intraepidermal NFD (ρ = -0.158; P = 0.5) or clinical symptoms (cold P = 0.1; prickling P = 0.2; burning P = 0.8; formication P = 0.7; stabbing P = 0.4; rubbing 0.1; pressure P = 0.1). The average dendritic cell density was increased in SFN (33.5 ± 57.5 cells/mm vs. 16.1 ± 13.7 cells/mm) but did not reach significance (P = 0.7).
CCM provides parameters that reliably indicate injury to sensory afferents of the trigeminal nerve in patients with SFN. Our data suggest that CCM may serve both as a noninvasive diagnostic test and as a surrogate marker in SFN.
[Show abstract][Hide abstract] ABSTRACT: Ocular prosthetics make a decisive contribution to the functional, esthetic and psychosomatic rehabilitation of patients after ocular extirpation.
This article provides an overview of the fitting, daily care and complications of ocular prosthetics.
The study comprised a PubMed literature review and own clinical results.
Ocular prosthetics made from cryolite glass or perspex can be manufactured and fitted 5-8 weeks after removal of the eye. During this period a conformer is placed within the conjunctival sac in order to prevent scar formation and shrinking of the socket. Artificial eyes can be worn continuously, only interrupted by a short but regular cleaning procedure. Artificial tears and lid hygiene improve the comfort of wearing. Glass prostheses have to be renewed every 1-2 years, while perspex prostheses need to be polished once a year. Complications, such as giant papillary conjunctivitis or blepharoconjunctivitis sicca are facilitated by poor fit, increased age and inappropriate care of the prosthetic device. In the case of socket shrinkage or anophthalmic socket syndrome, surgical interventions are needed to re-enable the use of an artificial eye.
Adequate fitting, daily care of ocular prosthetics and therapeutic management of associated complications are mandatory for a durable functional, esthetic and psychosomatic rehabilitation after ocular extirpation.
Der Ophthalmologe 07/2015; DOI:10.1007/s00347-015-0091-x · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thrombospondin-1 (TSP-1) is a matricellular glycoprotein that belongs to a family of evolutionary highly conserved calcium-binding proteins consisting of 5 members (TSP-1-TSP-5). In the eye, TSP-1 is expressed by several ocular cell types and is also detectable in the aqueous humor and the vitreous body. So far, TSP-1 is one of the major activators of TGFβ, suggesting a strong influence on various important cellular functions and interactions such as differentiation, migration, and wound healing. TSP-1 is also a key endogenous inhibitor of hem- and lymphangiogenesis. Several lines of evidence indicate a crucial role of TSP-1 in maintaining the ocular immune and angiogenic privilege, for example, by regulating T lymphocytes and the tolerance-promoting properties of ocular antigen-presenting cells. This review discusses the role of TSP-1 in dry eye disease and corneal graft rejection through its effects on hem- and lymphangiogenesis, as well as on the underlying immune responses. Recent work will be reviewed showing by which molecular mechanism TSP-1 modulates inflammatory processes during ocular diseases. This opens potential new treatment avenues in inflammatory and (lymph)angiogenic ocular diseases.
Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 07/2015; DOI:10.1089/jop.2015.0020 · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
In the murine cornea, which is an established model for analyzing pathologic lymphatic vessel growth, phenotypic heterogeneity of the endogenous lymphatic vessels in the limbus of the cornea was previously described. In this study, the cornea of BALB/c, C57BL/6, and FVB mice with different limbal lymphangiogenic phenotypes was analyzed to identify novel candidates potentially influencing lymphatic vessel growth.
Methods and results:
Pathway specific expression analysis of the cornea was performed to identify novel candidate genes. Corneal protein expression of the respective candidates was analyzed by fluorescent immunohistochemistry. The effect of the candidates on proliferation of human dermal lymphatic endothelial cells (HDLECs) was analyzed by BrdU proliferation ELISA. Thirteen genes were differentially regulated in corneas of mouse strains with more endogenous limbal lymphatic vessels (high-lymphangiogenic) (C57BL/6) compared to mouse strains with less endogenous limbal lymphatic vessels (low-lymphangiogenic) (BALB/c, FVB). Two candidates, Tumor necrosis factor (ligand) superfamily member 10 (Tnfsf10/Trail) and Plasminogen activator, tissue (Plat/tPA) were expressed in the cornea of BALB/c and C57BL/6 mice on the protein level. In vitro, Trail and recombinant tPA inhibited the proliferation of human dermal lymphatic endothelial cells.
Molecular analysis of the naive cornea in mouse strains with different limbal lymphatic phenotypes is a valuable model to identify novel endogenous regulators of lymphangiogenesis.
Lymphatic Research and Biology 06/2015; 13(2):76-84. DOI:10.1089/lrb.2015.0004 · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In posterior lamellar keratoplasties, such as Descemet membrane endothelial keratoplasty (DMEK) and Descemet's stripping automated endothelial keratoplasty (DSAEK) an air bubble is left inside the anterior chamber to promote graft attachment during the early postoperative period. In the case of insufficient graft adhesion a renewed intracameral air injection is often necessary. The use of sulfur hexafluoride diluted with air (SF6 20 %) as an alternative to pure air may further enhance graft attachment and reduce the rebubbling rate. The effect of SF6 20 % on corneal endothelium is currently unclear and was therefore examined in vitro.
For this study 12 human corneoscleral discs were mounted in artificial anterior chambers, the systems were continuously filled with culture medium and the anterior chambers with air (n = 5) or SF6 20 % (n = 7) as tamponade. After 6 days of storage in the incubator endothelial cell density, toxicity on endothelial cells and corneal thickness were evaluated.
There were no significant differences in endothelial cell loss (p = 1.000), endothelial cell count (p = 0.648), toxicity on endothelial cells (p = 0.048) and central corneal thickness (p = 0.905) between the two groups after 1 week. The level of significance was defined as p ≤ 0.05 and adjusted to p ≤ 0.0056 according to the Bonferroni correction for multiple testing.
The use of SF6 20 % as tamponade in the anterior chamber for posterior lamellar keratoplasty can be proposed as a safe alternative to pure air filling related to endothelial cell loss. Increased toxic effects on the corneal endothelium by SF6 20 % were not detected in this study; however, further prospective clinical trials are needed to examine the long-term effects in humans.
Der Ophthalmologe 05/2015; DOI:10.1007/s00347-015-0051-5 · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ocular GvHD is a severe complication following allogenic blood stem cell transplantation leading to massive reduction in quality of life and ocular pathologies including corneal perforation. Interdisciplinary patient-centred care needs to be performed in specialized ophthalmic centers that provide all diagnostic and therapeutic options, however, only few clinics have the necessary infrastructure. In addition there is a lack of transparency and easily accessible information for the patients regarding ophthalmic care and specialized centres. For this reason the "Ocular GvHD working group" within the Cornea Section of the German Society of Ophthalmology has been founded to evaluate and improve patient-centered care in ocular GvHD within Germany.
A survey was performed among the members of the Cornea Section of the German Society of Ophthalmology and the Directors of Departments of Ophthalmology in Germany that evaluated the number of annual examinations, presence of specialized GvHD outpatient clinics and eye screenings prior to allogenic blood stem cell transplantation (aBSCT).
25 clinics (19 university hospitals, 6 general hospitals) responded to the survey. In 18 clinics aBSCT are performed. Between 5 and 200 patients after aBSCT are examined per year per clinic. Larger institutions are associated with departments of haemato-oncology and other specialised disciplines to facilitate an interdisciplinary patient care. Three clinics are associated with GvHD competence centres. The major challenge in establishing an appropriate infrastructure for better patient-centered care is the limited or lacking reimbursement by health insurances.
Within Germany only few ophthalmic centres exist that provide state-of-the-art patient-centered care for ocular GvHD. The present structures are not sufficient to treat all patients undergoing aBSCT following existing guidelines. Joint efforts are necessary to establish more and accessible competence centers for ocular GvHD with sufficient personnel and structural resources. In addition, ocular GvHD should be included as a mandatory topic in medical training and transparent and easily accessible information needs to be provided for patients and health-care professionals.
Georg Thieme Verlag KG Stuttgart · New York.
[Show abstract][Hide abstract] ABSTRACT: Ocular graft-vs-host disease (GvHD) is a major complication following allogenic blood stem cell transplantation (aBSCT) leading to a disturbance of the ocular surface integrity with a broad range of severity. Leading symptom is a pronounced autoinflammatory reaction in particular at the ocular surface with typical features of dry eye disease. Potential complications include visual loss, pain and damage to the ocular structures with, e. g. corneal ulcerations. Diagnosis and treatment of ocular GvHD are a challenge for attending ophthalmologists and require intensive interdisciplinary patient care in particular with haemato-oncologists. First and follow-up examinations consist of several diagnostic steps that include quantitative and qualitative analysis of tearfilm, visual acuity, ocular surface and retinal integrity, cataract development and subjective symptoms. Available tests are mostly evaluated for usage in dry eye diagnosis but are, however, mostly unspecific for diagnosing ocular GvHD reliably. Only combinations of several clinical tests together with the experience of specialised ophthalmologists may lead to the certain diagnosis and treatment decisions at state. This review illustrates the available established and innovative non-invasive diagnostic tests and evaluates their potential use for diagnosing ocular GvHD.
Georg Thieme Verlag KG Stuttgart · New York.
[Show abstract][Hide abstract] ABSTRACT: Therapy for ocular graft-vs-host disease (ocular GvHD) is challenging for ophthalmologists as progress of the disease often occurs rapidly and is unforeseeable. Primary goal is the preservation or restoration of visual acuity, however, studies on ocular GvHD that have investigated therapeutic concepts are limited. In contrast, most therapeutic recommendations from consensus conferences derive from studies on dry eye diseases other than ocular GvHD. This review demonstrates the available therapies in the following categories: local, systemic, surgical and prophylactic. Primary targets are anti-inflammation, anti-fibrosis and lubrification of the ocular surface. In conclusion, studies strictly on ocular GvHD are needed to enable better evidence-based therapeutic decision-making in the future.
Georg Thieme Verlag KG Stuttgart · New York.