Interdisciplinary Surveillance of Ocular Melanomas: Experiences in a German Tertiary Centre. / Interdisziplinäre Tumornachsorge bei okulären Melanomen: Erfahrungen in einem Zentrum in Deutschland.

BACKGROUND: In contrast to cutaneous melanoma, there are no uniform guidelines regarding surveillance of ocular (uveal, conjunctival) melanomas. A consented standard operating procedure (SOP) by the "Netzwerk onkologische Spitzenzentren" Germany only exists for conjunctival melanoma but not for uveal melanoma. Surveillance is partially based on German S3-guidelines for cutaneous melanoma and is carried out by oncologic centres in a multidisciplinary approach. This study aims to evaluate patients' adherence to surveillance programs and whether surveillance recommendations (examinations, intervals) can be realised. METHODS: Retrospective analysis of all ocular melanoma patients overseen at the University Hospital of Cologne between 2008 and 2019. The study evaluates rates of successful patient integration into a standardized surveillance program and patients' surveillance adherence, subject to age, gender, primary therapy and tumour entity, respectively. RESULTS: 99 patients were included (56 female, 43 male), 83 of which had uveal melanomas and 16 conjunctival melanomas. Mean follow-up was 59 months. 81% of patients were integrated into a surveillance program. Surveillance was performed according to published recommendations in 78%. 13% of patients dropped out of the surveillance program after a mean period of 38 months. CONCLUSIONS: Our data show a growing number of patients in standardized surveillance. However, there are still gaps. There is a need for guidelines specifically designed for ocular melanomas, allowing centres to offer patients an individualized approach.

[Intubation Systems in Lacrimal Drainage Surgery - a Current Overview]. / Intubationssysteme in der Tränenwegchirurgie ­ eine aktuelle Übersicht.

The development of microendoscopes in lacrimal drainage surgery has led to the introduction of novel surgical procedures that maintain transcanicular anatomy, including a variety of lacrimal drainage intubation systems. Depending on the location and extent of the lacrimal duct stenosis, bicanaliculoanular, monocanalicular, monocanaliculonasal, bicanalicular, and bicanaliculonasal intubation techniques and systems, as well as a combination of these, may be used. For isolated intubation of the puncta lacrimalia, perforated punctum plugs may be used, while pure monocanalicular intubation can be performed using a Mini-Monoka. The monocanaliculonasal intubation systems include the Monoka (Wide Collarette type), Monoka of Fayet (Crawford type), the self-threading Monoka (Ritleng type), the Masterka, and the LacriJet for the ophthalmic surgeon. The bicanaliculonasal intubation systems include various BIKA systems, the Ritleng intubation system, the Crawford intubation system, and the FCI Nunchaku. Indications for both monocanaliculonasal and bicanaliculonasal intubation systems are obstructions, stenoses or lacerations of all kinds, as well as obstructions and stenoses after opening or after a DCR. For a conjunctivodacryocystorhinostomy (CDCR), the classical Lester Jones Tube, Metaireau Tubes, and StopLoss Jones Tube may be used. Although the study situation is ambiguous and therefore lacrimal drainage intubation is not considered mandatory, most ophthalmic surgeons do not forego intubation - despite the higher costs and slightly more protracted surgery. The surgeons' selection of the intubation system depends on the chosen form of intubation, costs and personal preferences and experience.

Cryolite glass prosthetic eyes-the response of the anophthalmic socket.

PURPOSE: To investigate mucoid discharge and the inflammatory response of anophthalmic sockets to cryolite glass prosthetic eye wear. PATIENTS AND METHODS: A total of 101 cryolite glass prosthetic eye wearers used visual analog scales (0-10) to measure frequency, color, volume, and viscosity of mucoid discharge associated with their prosthesis. Standardized photographs of the conjunctiva of their anophthalmic sockets were taken and conjunctival inflammation was semi-quantitatively graded (0-4). All characteristics of discharge and conjunctival inflammation were correlated to eye loss cause, hand washing behavior, and cleaning regimes as explanatory variables. RESULTS: Mean mucoid discharge characteristics (0-10 scale) were frequency 5.3 ± 2.8, color 4.8 ± 3.2, volume 4.9 ± 3.0, and viscosity 5.1 ± 3.2. The mean conjunctival inflammation score (0-4 scale) was 2.1 ± 1.0. There was a positive correlation between the grade of conjunctival inflammation and the frequency (p = 0.018), color (p = 0.001), volume (p = 0.003), and the viscosity of mucoid discharge (p = 0.005). More conjunctival inflammation was associated with higher frequency of cleaning (p < 0.001) and lower frequency of hand washing before removal (p = 0.001). Higher frequency, color, volume, and viscosity of discharge were associated with higher frequency of cleaning (p ≤ 0.001). CONCLUSIONS: Discharge severity associated with prosthetic eye wear was positively correlated with more conjunctival inflammation, higher cleaning frequency, and less hand washing before handling. The results suggest that cryolite glass eyes should not be removed daily for cleaning and that further research should be undertaken to develop a standardized treatment protocol for managing inflammation and mucoid discharge. This protocol would advise hand washing before handling cryolite glass eyes and recommend a minimum period of wear between cleaning sessions.

[Rehabilitation of Anophthalmic Patients with Prosthetic Eyes in Germany Today - Supply Possibilities, Daily Use, Complications and Psychological Aspects]. / Augenprothetische Rehabilitation in Deutschland heute ­ Versorgungsmöglichkeiten, Handhabung, Komplikationen und psychologische Aspekte.

BACKGROUND: A smooth supply with a visually appealing prosthetic eye after enucleation is not just a cosmetic solution, it is also a key factor in successful social and psychological rehabilitation. OBJECTIVES: This article provides an overview of the current state of medical and ocular care regarding prosthetic eyes in Germany. It focuses mainly on the newest clinical results, daily care, complications, and psychological aspects of wearing prosthetic eyes. METHODS: The study is comprised of the newest clinical results and a current PubMed literature review. RESULTS: In Germany, enucleated patients normally get a double-walled, hollow prosthetic eye made of cryolite glass, and patients with a microphthalmic or phthisic eye receive a thin single-walled prosthesis. Anophthalmic patients wearing cryolite glass prosthetic eyes seem to be more satisfied with their appearance and the look of their prostheses than polymethylmethacrylate (PMMA) prosthetic eye wearers. Cryolite glass prosthetic eyes must be renewed at least each year, while PMMA prostheses need to be polished once a year and renewed after five years of wearing. Among children, the fit of the prosthetic eye must be checked, based on growth, semi-annually. A slightly higher risk of breakage of cryolite glass prostheses is, for most patients, not a great disadvantage in everyday life. Ocularists and ophthalmologists should determine an individual cleaning regime, together with the patient, that is dependent on the material of the ocular prosthesis and other external factors. Complications, such as allergic, giant papillary, viral and bacterial conjunctivitis and blepharoconjunctivitis sicca must be treated at an early stage to allow for a prosthetic eye. In the case of inflammation-caused socket shrinkage or post-enucleation socket syndrome, surgical interventions are needed to re-enable the use of a prosthetic eye. Since the health of the remaining eye is the major psychological burden of prosthetic eye wearers, good ophthalmological care and medical screenings are essential elements. CONCLUSIONS: A smooth supply with a prosthetic eye, adequate and early treatment of possible complications and attention to psychological aspects is essential for successful long-term rehabilitation of enucleated patients.

[Diagnosis and Therapy of Iris Lesions]. / Diagnostik und Therapie von Irisläsionen.

The most common iris lesions are iris nevi, iris melanomas and iris pigment epithelium cysts. However, there is an abundance of rare differential diagnoses that have to be considered, including other melanocytic and non-melanocytic lesions. Diagnostic tools include the slit lamp examination, gonioscopy, tonometry, transillumination, ultrasound biomicroscopy (UBM), optical coherence tomography, fluorescein angiography and standardized photography-assisted documentation. The timely identification of malignant lesions (i.e. iris melanoma) is paramount. To assess malignancy criteria of iris nevi, the ABCDEF rule (age young, blood, clock hour inferior, diffuse growth, ektropion uveae, feathery margins) can be applied. Statistically, up to 11% of iris nevi may develop into iris melanomas within 20 years. TNM Staging follows the 2010 AJCC cancer staging manual and helps determine the optimal treatment strategy. Treatment options include radiotherapy, such as plaque brachytherapy and proton beam radiation therapy, as well as surgical excision. Both the surgical and the radiotherapeutic approaches show comparable local tumor control rates. However, the spectrum of therapy-related side effects and complications may differ amongst treatment modalities. After initial treatment, patients should be followed up every 3 - 6 months. Tumor-related mortality ranges between 0 - 11% and is significantly lower than in other uveal melanomas. A prognostic value of common genetic alterations, which have been identified as significant prognostic factors in posterior uveal melanoma, could not be shown for iris melanoma.

Association of RHAMM with E2F1 promotes tumour cell extravasation by transcriptional up-regulation of fibronectin.

Dissemination of cancer cells from primary to distant sites is a complex process; little is known about the genesis of metastatic changes during disease development. Here we show that the metastatic potential of E2F1-dependent circulating tumour cells (CTCs) relies on a novel function of the hyaluronan-mediated motility receptor RHAMM. E2F1 directly up-regulates RHAMM, which in turn acts as a co-activator of E2F1 to stimulate expression of the extracellular matrix protein fibronectin. Enhanced fibronectin secretion links E2F1/RHAMM transcriptional activity to integrin-ß1-FAK signalling associated with cytoskeletal remodelling and enhanced tumour cell motility. RHAMM depletion abolishes fibronectin expression and cell transmigration across the endothelial layer in E2F1-activated cells. In a xenograft model, knock-down of E2F1 or RHAMM in metastatic cells protects the liver parenchyma of mice against extravasation of CTCs, whereas the number of transmigrated cells increases in response to E2F1 induction. Expression data from clinical tissue samples reveals high E2F1 and RHAMM levels that closely correlate with malignant progression. These findings suggest a requirement for RHAMM in late-stage metastasis by a mechanism involving cooperative stimulation of fibronectin, with a resultant tumourigenic microenvironment important for enhanced extravasation and distant organ colonization. Therefore, stimulation of the E2F1-RHAMM axis in aggressive cancer cells is of high clinical significance. Targeting RHAMM may represent a promising approach to avoid E2F1-mediated metastatic dissemination.

[Excision and tectonic covering of a vascular leiomyoma of the ciliary body with large anterior staphyloma using scleral patch graft]. / Exzision und tektonische Deckung eines vaskulären Leiomyoms des Ziliarkörpers mit großem anteriorem Staphylom mittels Sklerapatch.

Benign tumors of the ciliary body are rare and may potentially be confused with uveal melanoma in clinical routine. Clinical findings rarely allow for safe differentiation. Hence primary excisions are frequent. We report the case of a patient with a benign ciliary tumor, which was observed over a total of 13 years and eventually underwent a local tumor resection.

[Young male patient with unusual space-occupying lesion of the lower eyelid]. / Junger Patient mit ungewöhnlicher Raumforderung am Unterlid.

BACKGROUND: A space-occupying lesion of the eyelid in young adults is often a sign of an inflammation, a trauma or a benign neoplasm. The aim of this case report is to demonstrate a rare basal cell carcinoma, which presumably already arose in adolescence without further high-risk factors. METHODS: A 28-year-old male patient presented for a second opinion on a painless swelling of the right lower eyelid. According to the patient's history the swelling had been present since the age of 16 years and originally resembled a molluscum contagiosum. An ophthalmologist in private practice made the diagnosis of a suspected trichoepithelioma. The extended patient history revealed a blood coagulation disorder. The clinical ophthalmological examination revealed a nodular space-occupying lesion with a border wall and telangiectasia. The further ophthalmological examination was bilaterally inconspicuous. Due to the suspicion of a malignant process, an operation was promptly carried out using local anesthesia with complete tumor excision and pedicled flap plasty as well as a histopathological investigation to confirm the diagnosis. RESULTS: The histopathological investigation revealed underlying infiltrates of a basaloid tumor with bale-shaped trabecular growth, sometimes with peripheral palisading of the cells. The cells were predominantly monomorphic with isolated pleomorphic nuclei and sometimes enclosed mitoses. Immunohistochemically the cells were strongly positive for BerEP4 and negative for epithelial membrane antigen (EMA). The diagnosis of a nodular basal cell carcinoma of the right lower eyelid was made. All incision margins were free of tumor cells (R0 resection). In the dermatological screening no further manifestations were detected. CONCLUSION: Despite the occurrence of a space-occupying lesion of the eyelid in a young adult patient and also with no further risk factors, in addition to an inflammatory event and a benign tumor, a malignant disease, such as a basal cell carcinoma should also be taken into consideration. A tissue biopsy or complete excision with subsequent histological examination including an immunohistochemical analysis are essential for differentiation from other tumor entities.

A Simple Standardized Three-Dimensional Anthropometry for the Periocular Region in a European Population.

BACKGROUND: The three-dimensional surface imaging system is becoming more common in plastic surgeries. However, few studies have assessed three-dimensional periocular structures and surgical outcomes. This study aimed to propose a standardized three-dimensional anthropometric protocol for the periocular region, investigate its precision and accuracy, and determine the three-dimensional periocular anthropometric norms for young Caucasians. METHODS: Thirty-nine healthy young Caucasians (78 eyes) were enrolled. Three-dimensional facial images were obtained with a VECTRA M3 stereophotogrammetry device. Thirty-eight measurements in periocular regions were obtained from these images. Every subject underwent facial surface capture twice to evaluate its precision. A paper ruler was applied to assess its accuracy. RESULTS: Sixty-three percent of measurements in linear distances, curvatures, angles, and indices were found to reach a statistically significant difference between sexes (p ≤ 0.05, respectively). Across all measurements, the average mean absolute difference was 0.29 mm in linear dimensions, 0.56 mm in curvatures, 1.67 degrees in angles, and 0.02 in indices. In relative error of magnitude, 18 percent of the measurements were determined excellent, 51 percent very good, 31 percent good, and none moderate. The mean value of the paper-ruler scale was 10.01 ± 0.05 mm, the mean absolute difference value 0.02 mm, and the relative error of magnitude 0.17 percent. CONCLUSIONS: This is the first study to propose a detailed and standardized three-dimensional anthropometric protocol for the periocular region and confirm its high precision and accuracy. The results provided novel metric data concerning young Caucasian periocular anthropometry and determined the variability between sexes.

Dry anophthalmic socket syndrome - Standardized clinical evaluation of symptoms and signs.

OBJECTIVES: To assess symptoms and signs of the dry anophthalmic socket syndrome (DASS) in a standardized manner. METHODS: 87 unilateral anophthalmic patients were evaluated using the Ocular Surface Disease Index (OSDI), the 5-Item Dry Eye Questionnaire (DEQ-5), and a modified version of Symptom Assessment iN Dry Eye (SANDE) questionnaire separately for the anophthalmic socket and for the healthy fellow eye. Conjunctival inflammation was semi-quantitatively graded and Schirmer I test with topical anesthesia was performed bilaterally. The correlations between scores of the dry eye questionnaires and the results of the Schirmer tests, conjunctival inflammation, and demographic data were examined. RESULTS: Patients had significantly higher OSDI, DEQ-5 and SANDE scores at the anophthalmic side compared to the healthy eye (p ≤ 0.019, respectively). 63% of patients complained of anophthalmic socket dryness in at least one of the three questionnaires. Patients had higher inflammation (p < 0.001) and more tear volume in the Schirmer I test with topical anesthesia (p ≤ 0.024) on the anophthalmic side compared to the fellow eye. CONCLUSIONS: Most anophthalmic patients have significantly more subjective dryness complaints on their anophthalmic side compared to the healthy fellow eye, even in absence of tear deficiency and clinical blepharitis. Eye care practitioners should consider the diagnosis criteria and the definition for DASS proposed in this study, when counseling anophthalmic patients. However, research should be undertaken to investigate the role and the interactions of causative etiological causes for DASS. Furthermore, there is a high priority to establish a standardized examination protocol and to develop an evidence-based treatment algorithm for DASS.

[Personalized medicine in the treatment of periocular tumors : Targeted treatment and use of immune checkpoint inhibitors]. / Personalisierte Medizin in der Behandlung von periokulären Tumoren : Zielgerichtete Therapien und der Einsatz von Immun-Checkpoint-Inhibitoren.

The aim of this article is to provide an overview on the current state of personalized medicine in the systemic treatment of selected periocular tumors, such as basal cell carcinoma, Merkel cell carcinoma and conjunctival melanoma. This article therefore provides an extensive current literature review from PubMed including the current guidelines and standard operating procedures (SOP). As 90% of basal cell carcinomas have a pathologic activation of the sonic hedgehog pathway, vismodegib is a new treatment option for inoperable or metastatic basal cell carcinoma and for patients with Gorlin-Goltz syndrome. A novel approach of systemic medicine for the treatment of metastatic Merkel cell carcinoma is immunotherapy using the immune checkpoint inhibitor avelumab. Other personalized immunotherapies, such as the checkpoint inhibitors pembrolizumab and nivolumab, the tyrosine kinase inhibitor pazopanib and the role of the hedgehog pathway in Merkel cell carcinomas are the subject of current research and will certainly play an important role in future treatment. In the narrow sense personalized medicine has only come true for metastatic conjunctival melanomas: systemic treatment with BRAF, MEK and/or checkpoint inhibitors is initiated only when a BRAF mutation is detected in the tumor or metastatic tissue. Systemic immunotherapy with the checkpoint inhibitors pembrolizumab and nivolumab can also be used as a treatment option in metastatic conjunctival melanomas. In summary, personalized medicine is a subject of current research and provides many new targeted treatment options especially for periocular malignancies; however, it also involves many great challenges in the development and implementation of new techniques and therapies.

[The role of ophthalmology in the COVID-19 pandemic]. / Die Rolle der Augenheilkunde in der COVID-19-Pandemie.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 19 (COVID-19) has led to a worldwide pandemic. This pandemic presents a huge challenge for the healthcare system and also for ophthalmologists. Previous studies and case reports indicated that SARS-CoV­2 also infects the conjunctiva resulting in conjunctivitis. In addition, infectious virus particles in the tear fluid can be potential sources of infection; however, the detection of SARS-CoV­2 RNA in the tear fluid has rarely been successful. Although isolated conjunctival involvement is highly unlikely, at the current point in time of the COVID-19 pandemic, practically every patient examined by an ophthalmologist could be infected with SARS-CoV­2. Therefore, protective and hygiene measures should currently be consistently followed to minimize the risk of spreading the virus. Currently, there are no treatment recommendations for conjunctivitis associated with COVID-19. Tear substitutes might be helpful for symptom relief but there is no evidence for a topical antiviral therapy. In the future ophthalmologists could play a decisive role in the screening of maculopathies that might occur during COVID-19 treatment using chloroquine or hydroxychloroquine.

Sentinel lymph node biopsy in the management of conjunctival melanoma: current insights.

Purpose: To evaluate the role of sentinel lymph node biopsy (SLNB) in conjunctival melanoma (CM). Methods: This article provides a review of the literature from PUBMED. Results: Data on SLNB in the management of CM are scarce and only two relatively large cohorts have been reported. Although indication criteria for SLNB vary slightly, positive findings can be expected in 11%-13% of CM cases, including small tumors. False negative SLNB findings are rare (<10%). Failure to identify SLNB has been attributed to the surgical learning curve and recurrent tumors with scar tissue impeding spread of the tracer material. Reported 5-year survival rate following CM management including SLNB, is up to 79%, but there are no comparative cohort studies proving the assumed benefit. Adverse events reported were non-severe and transient. Conclusion: Patients can potentially benefit from SLNB and the procedure can be offered to eligible patients. However, there is not enough evidence to support SLNB as a mandatory part of CM management.

Customizing a Cryolite Glass Prosthetic Eye.

In Germany, Austria, and Switzerland, over 90% of ocularists still manufacture customized prostheses using cryolite glass from Thuringia. The present manuscript demonstrates this long-forgotten technique in detail. This manuscript shows some major advantages of manufacturing prosthetic eyes using cryolite glass in comparison to poly(methyl methacrylate) (PMMA). These advantages include a lighter weight of the prosthesis, higher levels of patient satisfaction, and only one appointment necessary for the customized manufacturing. Potential risk of breakage seems not to be a critical disadvantage for glass prosthetic eye wearers. However, in some patients, manufacturing a well-fitting prosthetic eye is not possible or reasonable due to anophthalmic socket complications such as post nucleation socket syndrome, scarred fornices, or an orbital implant exposure. This article gives ophthalmologists a better insight into ocularistic care in order to improve the essential interprofessional collaboration between ocularists and ophthalmologists.

Transcanalicular laser dacryocystorhinostomy for acquired nasolacrimal duct obstruction: an audit of 104 patients.

PURPOSE: External dacryocystorhinostomy (DCR) is considered as the gold standard in the treatment of acquired nasolacrimal duct obstruction. However, many advances have been made towards the development of modern minimally invasive therapies. These new techniques were proven less harmful to the patients' skin and medial palpebral structures with their palpebral-canalicular pump mechanism. Options include endonasal and transcanalicular procedures. Here, we report on our 2-year experience with the surgical technique, results and complications of transcanalicular laser-assisted DCR. METHODS: This is a retrospective study. A total of 104 patients with acquired nasolacrimal duct obstruction underwent transcanalicular laser-assisted DCR combined with bicanalicular silicon intubation. We then analyzed intra-/post-operative complications and subjective and objective success rates. The institutional ethics committee ruled that approval was not necessary. The trial was registered with the German Clinical Trials Register (DRKS00012879). RESULTS: Transcanalicular laser-assisted DCR in combination with bicanalicular silicon intubation could be performed surgically successfully in 101 patients (97%). In three cases (3%) using the superior canalicular approach, positioning of the laser instrument at the anteroinferior rim of the middle turbinate failed. Complications included thermal injury to the canaliculus (one), canalicular infection (two) and silicon tube prolapse (ten). Functional success (resolution of preoperative symptoms) was achieved in 80 cases (77%), functional failure occured in 24 cases with all patients reporting persisting epiphora, 15 reporting failure to irrigate the nasolacrimal duct and 15 requiring secondary external DCR. CONCLUSIONS: Laser-assisted DCR shows promising results with few complications. It seems well suited as a second-step procedure after failed recanalization and before external DCR.

Systemic BRAF/MEK Inhibitors as a Potential Treatment Option in Metastatic Conjunctival Melanoma.

AIM: In this review, we outline similarities between conjunctival and skin melanoma as well as the effectiveness of combined BRAF/MEK inhibition in melanoma, and discuss the applicability of these agents in conjunctival melanoma. METHODS: The study provides a PubMed literature review. RESULTS: Conjunctival melanoma and skin melanoma are genetically and phenotypically related. Both tumors typically harbor BRAF mutations in more than 50% of cases. New targeted therapies in metastatic skin melanoma include selective inhibition of BRAF and MEK. Combined BRAF/MEK inhibition has revolutionized the treatment of metastatic skin melanoma, significantly improving patients' prognoses. While these new substances have been investigated extensively in the treatment of skin melanoma, comparable studies in conjunctival melanoma do not exist owing to the rarity of the malignancy. CONCLUSIONS: The application of combined BRAF/MEK inhibition in metastatic or unresectable conjunctival melanoma shows great potential for improving patients' prognoses. Future studies are needed to investigate the assumed benefit.

Transcanalicular Diode Laser-assisted Dacryocystorhinostomy for the Treatment of Primary Acquired Nasolacrimal Duct Obstruction.

Today's gold standard in the treatment of infrasaccal primary acquired nasolacrimal duct obstruction (PANDO) is external dacryocystorhinostomy (DCR), a relatively invasive procedure that can be performed after failure of recanalizing treatments. However, with progress in the field of diode laser technology, new approaches have emerged. Laser-assisted transcanalicular DCR with subsequent bicanalicular silicon intubation is a new option showing great promise as a viable minimally invasive procedure. Under permanent endoscopic visual control from the nasal cavity, a diode laser fiber is inserted into the lacrimal sac and laser energy is applied to create a bony ostium between the lacrimal sac and the nasal cavity. Since no skin incision needs to be made, advantages of this method comprise the sparing of the skin as well as the medial palpebral structures and the physiological palpebral-canalicular pump mechanism. The duration of surgery as well as reconvalescence is generally shorter than with external DCR. Complications include silicon tube prolapse, mild swelling and, rarely, canalicular infection and thermal injury. One-year functional success rates, defined as complete resolution of symptoms and ostium patency, are high, yet still range behind those of external DCR. However, secondary external DCR after failure of laser-assisted DCR can be performed without difficulty. Thus, laser-assisted transcanalicular DCR is a valid option that should be considered as a second-step procedure after failure of recanalization procedures and before external DCR.