[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: Background: External dacryocystorhinostomy (DCR) is at present the gold standard for the surgical treatment of acquired nasolacrimal duct obstructions, but tremendous progress has been made in recent years in improving minimally invasive techniques, sparing not only the skin, but also the medial lid structures, which contribute to the physiological palpebral-canalicular pump mechanism. The purpose of this study is to report our 1-year experience with the surgical technique, complications and results of transcanalicular laser assisted DCR. Patients and Methods: 48 consecutive transcanalicular laser-assisted DCRs combined with bicanalicular silicone intubation were performed for acquired nasolacrimal duct obstruction, and evaluated for intra- and postoperative complications, as well as subjective and objective success rates. Results: Transcanalicular laser-assisted DCR combined with bicanalicular silicone intubation was surgically feasible in 45 cases (94 %). In 3 patients (6 %) it was impossible to position the aiming beam correctly at the anteroinferior rim of the middle turbinate using the superior canalicular approach, due to superior orbital rim prominence. Therefore 2 patients received no silicone intubation, despite a patent osteotomy at the back of the middle turbinate, and 1 patient underwent intraoperative conversion to external DCR due to anatomical narrowness of the nasal cavity. Perioperatively, 1 patient developed canalicular infection, 1 patient exhibited thermal injury to the canaliculus, and 4 patients exhibited premature prolapse of the silicone tube. At 6-months follow-up, functional success - defined as resolution of preoperative symptoms - was achieved in 35 of 45 surgically successful transcanalicular laser-assisted DCRs (78 %). Of the 10 postoperative failures (22 %), all patients reported epiphora, 6 patients were unable to irrigate the lacrimal drainage system, and 6 patients required surgical revision using external DCR. Conclusions: Transcanalicular laser assisted DCR is a promising minimally invasive approach for the surgical treatment of acquired nasolacrimal duct obstruction, in order to fill the gap between recanalising first step procedures and external DCR.
Klinische Monatsblätter für Augenheilkunde 11/2015; DOI:10.1055/s-0041-106653 · 0.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Uveal melanomas are the most common malignant tumors of the eye. With modern molecular biological diagnostic methods, such as chromosome 3 typing and gene expression analysis, these tumors can be categorized into highly aggressive (monosomy 3, class II) and less aggressive forms. This molecular biological stratification is primarily important for determining the risk of these tumors as no therapy is currently available that is able to prevent or delay metastases. A randomized study of patients with a poor prognosis (monosomy 3) is currently being carried out in order to determine whether a cancer vaccine prepared from autologous (patient's own) dendritic cells and uveal melanoma RNA can prevent or delay progression and further metastases of this extremely aggressive form of cancer. Inclusion in the uveal melanoma study, which hopes to provide a potential therapeutic option for patients, is only possible if patients are referred to an institution that is able to manufacture and provide this vaccination before the patient is operated on or treated with radiation. Untreated tumor material is necessary for producing the vaccine on an individualized patient basis.
Der Ophthalmologe 11/2015; DOI:10.1007/s00347-015-0162-z · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To monitor the intraocular pressure (IOP) changes immediately after anterior chamber air tamponade in Descemet membrane endothelial keratoplasty (DMEK).
Twenty-four patients undergoing DMEK and 16 patients undergoing rebubbling after DMEK were enrolled (n = 40). All DMEK patients had inferior iridectomy and nearly full intracameral air tamponade with an aimed IOP of 25 mm Hg at the end of surgery. The IOP was measured at 1, 2, 3, 5, 12, 24 hours and 1 week postoperatively.
After anterior chamber air fill in DMEK, the IOP increased from preoperative baseline, 12.1 ± 2.9 mm Hg, to 26.3 ± 4.7 mm Hg, P < 0.001. Mean IOP was significantly elevated in the first 2 hours, 19.4 ± 10.5 mm Hg and 17.0 ± 7.4 mm Hg, P = 0.007 and 0.006, respectively. Then, it lowered to the baseline level, 14.0 ± 4.7 mm Hg, P > 0.05, and remained stable during follow-ups. An asymptomatic IOP elevation above 30 mm Hg was detected in 3 patients (12.5%) within the first 2 hours. None had preexisting glaucoma. Most episodes could be controlled by antiglaucoma medications and upright positioning. The pattern of IOP changes after rebubbling was similar to that after DMEK but the IOP dropped sharply to the baseline level after 1 hour and had no incidence of IOP elevations beyond 30 mm Hg.
Adequate inferior iridectomy greatly alleviates the risk and severity of acute IOP rises after nearly full anterior chamber air tamponade in DMEK. Standard IOP adjustment at the end of DMEK surgery with postoperative IOP monitoring especially in the first 2 postoperative hours is advisable when there is no postoperative default air release.
[Show abstract][Hide abstract] ABSTRACT: Ultraviolet light B (UVB)-irradiation is linked to various ocular pathologies such as limbal stem cell defects in pterygium. Despite the large circumstantial evidence linking UVB irradiation and limbal epithelial stem cell damage, the precise molecular responses of limbal stem cells to UVB irradiation are unclear. Here the effect of UVB irradiation on the putative stem cell phenotype, limbal niche cells and the subsequent effects on corneal (lymph)angiogenic privilege were investigated. Primary human limbal epithelial stem cells and fibroblasts were irradiated with 0.02J/cm(2) of UVB, a low dose corresponding to 3min of solar irradiation. UVB irradiation caused significant reduction of limbal epithelial and limbal fibroblast proliferation for 24h, but apoptosis of limbal epithelial stem cells only. Moreover, UVB induced stem-like character loss of limbal epithelial cells, as their colony forming efficiency and putative stem cell marker expression significantly decreased. Interestingly, limbal epithelial cells co-cultured with UVB-irradiated limbal fibroblasts also exhibited loss of stem cell character and decrease of colony forming efficiency. Conditioned media from limbal epithelial cells inhibited lymphatic endothelial cell proliferation and tube network complexity; however this effect diminished following UVB irradiation. In contrast, pro-inflammatory and macrophage-recruiting cytokines such as TNFα, IFNγ and MCP1 were significantly upregulated following cell irradiation of limbal fibroblasts. These data demonstrate the key role of the limbal stem cell niche in response to UVB and subsequent (lymph)angiogenic and inflammatory events. These data suggest that the known pro(lymph)angiogenic effect of UVB irradiation in pterygium is not linked to a direct up-regulation of pro-angiogenic cytokines, but rather to indirect macrophage-recruiting cytokines being upregulated after UVB irradiation.
Stem Cell Research 11/2015; 15(3):643-654. DOI:10.1016/j.scr.2015.10.008 · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of IL-10, a primarily anti-inflammatory cytokine, in the regulation of inflammatory lymphangiogenesis is undetermined. Herein, we show that IL-10 modulates corneal lymphangiogenesis and resolution of inflammation. IL-10 was not expressed in healthy corneas but was up-regulated in inflamed corneas by infiltrating macrophages. Macrophages up-regulated the expression of prolymphangiogenic vascular endothelial growth factor-C on stimulation with IL-10. Consistently, corneal inflammation resulted in reduced expression of vascular endothelial growth factor-C and decreased corneal lymphangiogenesis in IL-10-deficient mice (IL-10(-/-)). The effect of IL-10 on lymphangiogenesis was indirect via macrophages, because IL-10 did not affect lymphatic endothelial cells. The expression of proinflammatory cytokine and the numbers of infiltrating macrophage increased and remained elevated in inflamed corneas of IL-10(-/-) mice, indicating that IL-10 deficiency led to more severe and prolonged inflammation. The corneal phenotype of IL-10 deficiency in mice mimicked conditional deletion of Stat3 in myeloid cells (lysozyme M Cre mice Stat3(fl/fl)), corroborating the critical role of macrophages in the regulation of lymphangiogenesis. Furthermore, local treatment with IL-10 promoted lymphangiogenesis and faster egress of macrophages from inflamed corneas. Taken together, we demonstrate that IL-10 indirectly regulates inflammatory corneal lymphangiogenesis via macrophages. Reduced lymphangiogenesis in IL-10(-/-) and lysozyme M Cre mice Stat3(fl/fl) is associated with more severe inflammatory responses, whereas IL-10 treatment results in faster resolution of inflammation. IL-10 might be used therapeutically to terminate pathological inflammation.
American Journal Of Pathology 11/2015; DOI:10.1016/j.ajpath.2015.09.012 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Despite microscopically controlled tumor excision, malignant melanomas of the conjunctiva have a propensity for local recurrence, lymphatic spread and distant metastases.
This review outlines the options of adjuvant therapy as well as the structure of interdisciplinary follow-up care for patients with conjunctival melanoma.
The study provides a PubMed literature review and own clinical results.
In conjunctival melanoma complete tumor excision using a minimal touch technique should always be combined with adjuvant therapy, such as cryotherapy, radiotherapy, topical chemotherapy and/or immunotherapy. For locally circumscribed lesions of the bulbar conjunctiva adjuvant brachytherapy can be supplemented and for non-bulbar, extensive, diffuse or multilocular tumor growth, complementary adjuvant topical mitomycin C therapy or proton radiotherapy can be used. Novel adjuvant approaches include topical interferon alpha-2b immunotherapy, topical vascular endothelial growth factor (VEGF) inhibitors or in cases of BRAF mutations personalized therapy using selective BRAF inhibitors or in combination with mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK), MAPK/ERK (MEK) inhibitors. All patients should be integrated into an interdisciplinary follow-up care program including quarter yearly checkups in the first 5 years and psycho-oncological healthcare.
Following microscopically controlled tumor excision, adjuvant treatment using cryotherapy, radiotherapy, topical chemotherapy and/or immunotherapy as well as interdisciplinary follow-up care are mandatory for the modern management of patients with conjunctival melanoma.
Der Ophthalmologe 10/2015; 112(11). DOI:10.1007/s00347-015-0141-4 · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The Cutler-Beard bridge flap technique is an established method for reconstruction of large full thickness upper eyelid defects. The purpose of the present study was to report experiences with the surgical technique, complications and results of this cutaneoconjunctival flap procedure following tumor resection.
Patients and methods:
A total of 18 patients with extensive full thickness upper eyelid defects after tumor excision underwent a Cutler-Beard procedure. Of the patients four received an additional eye bank scleral implant and one received an additional free tarsal graft from the fellow upper eyelid to enhance eyelid stability.
The Cutler-Beard bridge flap technique was surgically feasible in all patients without causing damage to the lower eyelid bridge or resulting in any infections. Out of the 13 reconstructions without additional stabilizing tissue 3 (23 %) developed an upper eyelid entropion that was successfully managed using a secondary scleral implant. None of the five reconstructions using additional scleral or tarsal tissue showed an entropion of the upper eyelid.
The Cutler-Beard bridge flap technique, which can be combined with grafting additional stabilization tissue in defects exceeding 75 % of the upper eyelid length, is a reliable method for reconstruction of large full thickness upper eyelid defects following tumor excision.
Der Ophthalmologe 10/2015; DOI:10.1007/s00347-015-0146-z · 0.50 Impact Factor
[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.