Histopathological findings of failed blebs after microinvasive bleb surgery with the XEN Gel Stent and Preserflo MicroShunt.

PURPOSE: The success of XEN Gel Stent (XEN) and Preserflo MicroShunt (Preserflo) implantation depends mainly on the development of bleb fibrosis. This study aimed to describe the histological findings of bleb fibrosis after XEN and Preserflo surgery. METHODS: This retrospective study included patients with different types of glaucoma who underwent revision surgery after XEN or Preserflo implantation. The available clinical information and histological samples of removed fibrotic tissue were analyzed. RESULTS: Thirty-six patients were included. Revision surgery was performed at a median of 195 (range = 31-1264) days after primary surgery. The mean intraocular pressure changed from 29.1 (± 10.3) mmHg at baseline to 18.3 (± 8.7) mmHg (- 37%; p < 0.0001) and 16.2 (± 4.2) mmHg (- 45%; p < 0.0001) after 6 and 12 months, respectively. Histological analysis revealed an increase in activated fibroblasts and macrophages in all specimens and a parallel orientation of fibroblasts in a minor part of the probe in 60% of the specimens. No pronounced inflammatory reaction in the form of lymphocytic or granulocytic infiltration was observed. The comparison of specimens from uveitic glaucoma and primary open-angle glaucoma patients revealed no significant differences. CONCLUSIONS: The histological analysis of fibrotic blebs from the XEN and Preserflo implants did not show any pronounced immune or foreign-body reaction and revealed a similar histological pattern of failed blebs after trabeculectomy.

TRPP2 is located in the primary cilia of human non-pigmented ciliary epithelial cells.

PURPOSE: Mechanosensitive channels (MSCs) and primary cilium possess a possible relevance for the sensation of intraocular pressure (IOP). However, there is only limited data on their expression and localization in the ciliary body epithelium (CBE). The purpose of this study was to characterize the expression and localization of TRPP2 in a human non-pigmented ciliary epithelial cell (HNPCE) line. METHODS: The expression of the TRPP2 was studied by quantitative (q)RT-PCR and in situ hybridization in rat and human tissue. Protein expression and distribution were studied by western blot analysis, immunohistochemistry, and immunoelectron microscopy. Cellular location of TRPP2 was determined in rat and human CBE by immunofluorescence and immunoblot analysis. Electron microscopy studies were conducted to evaluate where and with substructure TRPP2 is localized in the HNPCE cell line. RESULTS: The expression of TRPP2 in rat and human non-pigmented ciliary epithelium was detected. TRPP2 was mainly located in nuclei, but also showed a punctate distribution pattern in the cytoplasm of HNPCE of the tissue and the cell line. In HNPCE cell culture, primary cilia did exhibit different length following serum starvation and hydrostatic pressure. TRPP2 was found to be colocalized with these cilia in HNPCE cells. CONCLUSION: The expression of TRPP2 and the primary cilium in the CB may indicate a possible role, such as the sensing of hydrostatic pressure, for the regulation of IOP. Functional studies via patch clamp or pharmacological intervention have yet to clarify the relevance for the physiological situation or aqueous humor regulation.

Choroidal metastases from thymic carcinoma during pregnancy: Case Report.

BACKGROUND: Rare sites of metastases, atypical symptoms and paraneoplastic syndromes are often neglected or misinterpreted, especially when they represent early symptoms of an underlying malignant disease. Hence, an interdisciplinary approach to these patients is essential to avoid tumor progression and metastatic spread in order to provide curative treatment options to the patients. We here report the case of a young woman presenting with visual loss which led to diagnosis of a thymic carcinoma. CASE PRESENTATION: A 28-year old white woman presented with subacute loss of vision in the last trimester of her first pregnancy which was first interpreted as an exacerbation of a pre-existing dermatomyositis and treated with steroids. After failure of steroid therapy choroidal metastases from an undifferentiated thymic carcinoma were diagnosed. This also shed a new light on the dermatomyositis the patient had been suffering from for seven years possibly representing a paraneoplastic syndrome from the tumor. Despite aggressive chemotherapy, the patient died from progressive disease eight years after first onset of dermatomyositis and 14 months after initial diagnosis of the thymic carcinoma. CONCLUSIONS: Choroidal metastases from a thymic carcinoma have never been reported before but should be included into the differential diagnosis of choroidal masses.

Critical evaluation of the usability of augmented reality ophthalmoscopy for the training of inexperienced examiners.

PURPOSE: To measure the value of augmented reality technology usage to teach the medical students performing binocular indirect ophthalmoscopy. METHODS: Thirty-seven medical students were randomly assigned to the training of binocular indirect ophthalmoscopy either in the conventional way or with augmented reality ophthalmoscopy (ARO). For testing student's skills, they had to examine a real person using a conventional ophthalmoscopy system and draw the optic disk. They also had to fill out a questionnaire. Subjective and objective evaluations were performed. RESULTS: Thirty-seven students were randomly assigned to two groups. Eighteen students were trained with conventional ophthalmoscopy and 19 students with ARO. The questionnaires showed no differences. Performing an objective analysis, the median ophthalmoscopy training score for the conventional ophthalmoscopy group was 1.2 (range, 0.67-2) and showed a significant difference (P < 0.0033) to the ARO group (median 2; range, 0.67-2). CONCLUSION: The study provides evidence that a single ARO training is efficient to improve ophthalmoscopy skills. As the objective analysis showed, the ARO group had a significantly superior performance. Our study also indicates that subjective evaluation of the fundus drawings without systematic analysis is prone to errors.

Cataract formation: a possible complication of intra-arterial chemotherapy for retinoblastoma.

PURPOSE: To delineate and discuss a not yet described possible ocular complication of selective intra-arterial chemotherapy (SIAC) for treatment of retinoblastoma. METHODS: A 23-month-old girl with a large unilateral retinoblastoma was treated with repeated SIAC using 5 mg melphalan between July 2010 and January 2012. Clinical course of tumor and further ocular changes after therapy and histopathologic findings are described. RESULTS: In total, 5 SIAC were performed over a time period of 18 months. After the last SIAC, diffuse dense cataract prevented further funduscopy. In addition, anterior chamber seeding was obvious, leading to the decision to enucleate the eye. Histopathologically, nearly complete regression of the main tumor mass with prominent calcifications, but vital tumor seeding in the vitreous, on the lens surface, on the ciliary body, and in the anterior chamber, was observed. Peculiar vacuolation of the lens epithelial cells, liquefaction of the subepithelial lens fibers, and diffuse small vacuoles within the lens were striking. CONCLUSIONS: Repeated SIAC with melphalan may induce cataract formation, possibly as a toxic effect of the chemotherapeutic to the lens, maybe combined with radiation exposure during fluoroscopy. This ocular complication should be taken into consideration as a limitation of the number of feasible repeated treatments.

Pars plana vitrectomy for treatment of advanced Coats' disease--presentation of a modified surgical technique and long-term follow-up.

BACKGROUND: To present a modified surgical technique in the treatment of retinal detachment secondary to advanced Coats' disease in children, and report on long-term anatomical and functional outcome. METHODS: We analysed an interventional case series of 13 patients (13 eyes) with advanced Coats' disease characterised by retinal detachment in addition to massive subretinal exudates and vascular malformation. The presented patients underwent pars plana vitrectomy (PPV), including a modified technique of exocryotherapy applied after fluid-air exchange in order to achieve complete treatment of the vascular changes, to reduce associated side-effects, and to avoid retinectomy and silicone oil tamponade. RESULTS: Within a median follow-up period of 37 months (range: 18-66 months), no enucleation was necessary. Four eyes (31 %) did not need any further therapy, and in nine eyes (69 %) additional treatments were performed. Six patients (46 %) required revisional surgery with silicone oil tamponade. In ten eyes (77 %), the pathologic vessels and exudates finally regressed and the retina reattached. Visual acuity (VA) could be stabilized in the majority of patients: in three eyes (27 %) VA improved, in four eyes (36 %) VA remained stable, in four eyes (36 %) visual acuity (VA) deteriorated, and in two eyes VA could not be evaluated. CONCLUSIONS: The presented modified technique allows for sufficient cryotherapy of vascular malformations, even in the presence of massive exudation, in a subset of patients with advanced Coats' disease, and thus may reduce surgery-related complications and improve the rehabilitation process of these young patients.

Retrospective evaluation of patients with uveal melanoma treated by stereotactic radiosurgery with and without tumor resection.

IMPORTANCE: The present study intended to analyze the suitability of single-dose stereotactic radiotherapy in the treatment of uveal melanoma that cannot be handled with ruthenium-brachytherapy and therefore is a challenge for ophthalmologists concerning local tumor control, as well as preservation of the eye and visual function. OBJECTIVES: To evaluate local tumor control, eye preservation, visual course, radiation complications, metastases, and death after single-dose stereotactic radiotherapy (SDRT) applied exclusively or combined with tumor resection in uveal melanomas that are neither suitable nor favorably located for ruthenium brachytherapy. DESIGN: Retrospective, observational case series. SETTING: Primary care center. PARTICIPANTS: Seventy-eight patients with uveal melanoma were treated. INTERVENTION: Between June 3, 2003, and March 18, 2008, patients with uveal melanoma received SDRT monotherapy (group 1, 60 patients) or SDRT combined with tumor resection (group 2, 18 patients). Radiotherapy was performed with a tumor-surrounding dose of 25 Gy on a linear accelerator. MAIN OUTCOME MEASURES: Local tumor control, eye preservation, visual results, and radiation complications. RESULTS: Within a median follow-up of 33.7 months (range, 0.13-81.13 months), 6 recurrences occurred in group 1; none recurred in group 2. The Kaplan-Meier estimate for local control was 85% at 3 years in group 1 and 100% in group 2 (P = .22). Eye preservation rate was 77% vs 87% at 3 years (groups 1 and 2, respectively) (P = .82). Visual acuity decreased with a median loss of -18 Snellen lines (group 1) and -22 Snellen lines (group 2). More retinopathies (P = .07), opticopathies (P = .27), and rubeotic glaucomas (P = .10) occurred in group 1. No significant difference was observed in the development of metastases (P = .33). The groups differed in overall survival because of 2 deaths occurring shortly after surgery in group 2 for unexplained reasons (P = .06). CONCLUSIONS AND RELEVANCE: Survival analysis suggested that SDRT with combined tumor resection might be associated with increased tumor control and fewer radiation complications than SDRT as monotherapy. Both groups had similar eye retention rates and were comparable concerning the decrease in visual function in most eyes. However, the protocol was stopped after 3 unexplainable deaths after surgery.

Sulcus anatomy and diameter in pseudophakic eyes and correlation with biometric data: evaluation with a 50 MHz ultrasound biomicroscope.

PURPOSE: To evaluate the sulcus anatomy and possible correlations between sulcus diameter and white-to-white (WTW) diameter in pseudophakic eyes, data that may be important in the stability of add-on intraocular lenses (IOLs). SETTING: University Eye Hospital, Tuebingen, Germany. DESIGN: Case series. METHODS: In pseudophakic eyes, the axial length (AL) and horizontal WTW were measured by the IOLMaster device. Cross-sectional images were obtained with a 50 MHz ultrasound biomicroscope on the 4 meridians: vertical, horizontal (180 degrees), temporal oblique, and nasal oblique. Sulcus-to-sulcus (STS), angle-to-angle (ATA), and sclera-to-sclera (ScTSc) diameters were measured. The IOL optic diameter (6.0 mm) served as a control. To test reliability, optic measurements were repeated 5 times in a subset of eyes. RESULTS: The vertical ATA and STS diameters were statistically significantly larger than the horizontal diameter (P=.0328 and P=.0216, respectively). There was no statistically significant difference in ScTSc diameters. A weak correlation was found between WTW and horizontal ATA (r = 0.5766, P<.0001) and between WTW and horizontal STS (r = 0.5040, P=.0002). No correlation was found between WTW and horizontal ScTSc (r = 0.2217, P=.1217). CONCLUSIONS: The sulcus anatomy had a vertical oval shape with the vertical meridian being the largest, but it also had variation in the direction of the largest meridian. The WTW measurements showed a weak correlation with STS. In pseudophakic eyes, Soemmerring ring or a bulky haptic may affect the ciliary sulcus anatomy.

GDF-15: a novel serum marker for metastases in uveal melanoma patients.

BACKGROUND: About 50% of patients with uveal melanoma (UM) develop metastases during the course of their disease. We analyzed serum levels of Growth Differentiation Factor-15 (GDF-15), with the aim of identifying patients with early metastases. METHODS: GDF-15 concentration was measured using an enzyme-linked immunosorbent assay (ELISA) in serum samples from 188 UM patients (170 patients without metastases; 18 patients with clinically detectable metastases) and 18 healthy control individuals. Data were analyzed with respect to differences between patients with and without clinically detectable UM metastases. GDF-15 serum levels were further analyzed with regard to significant patient and tumor characteristics as revealed by histology and multiplex ligation-dependent probe amplification (MLPA) to determine chromosome 3 copy number. GDF-15 expression in UM was investigated by immunohistochemistry. RESULTS: Patients with clinically detectable metastases had significantly higher GDF-15 serum levels compared to those without clinically detectable metastases as well as to healthy individuals (ANOVA; p < 0.001). GDF-15 concentrations in UM patients with overt clinically detectable metastases were significantly higher than those in UM patients with a second malignancy in remission but without clinically detected UM metastases (ANOVA; p < 0.001). No association between serum concentration of GDF-15 and clinical, pathological, and genetic features was observed. GDF-15 protein was only expressed in a minority of UM cells in most tumors. CONCLUSIONS: Our data suggest that GDF-15 can be used as a serum marker for the diagnosis of metastases in UM patients. Further data collection and analysis are necessary to evaluate a possible prognostic role of GDF-15 in predicting early metastases.

Circulating melanoma cells in peripheral blood of patients with uveal melanoma before and after different therapies and association with prognostic parameters: a pilot study.

PURPOSE: To evaluate whether tumour therapy for malignant uveal melanoma leads to a shedding of melanoma cells into the systemic circulation. METHODS: Ninety-four peripheral blood samples from 81 patients with malignant uveal melanoma were collected before and after different tumour therapies and the number of circulating melanoma cells (CMCs) was investigated (seven patients with enucleation, 49 patients with stereotactic radiotherapy, 19 patients with endoresection of the tumour, 15 patients with ruthenium-brachytherapy and four patients with transpupillary thermotherapy). A cellular approach was used to detect CMCs through an immunocytological assay with tumour cell enrichment by immunomagnetic cell sorting. The number of CMCs was analysed further according to specific patient characteristics, tumour parameters and the development of metastasis. RESULTS: There was no significant difference between the number of CMCs before and after the different therapies (p = 0.78). There was also no significant association between established prognostic parameters of primary uveal melanoma and the detection of CMCs (all p >0.05). The number of CMCs was not related to the development of metastasis in a short median follow-up time of 16 months (p > 0.05). CONCLUSION: No changes in CMC values were observed before and after different tumour therapies. In the majority of cases therapy does not lead to a shedding of detectable melanoma cells into the systemic circulation.

Choroidal neovascular membrane after endoresection of choroidal melanoma.

PURPOSE: The purpose of this study was to report two cases with choroidal melanoma who underwent endoresection and developed choroidal neovascular membrane (CNVM) during follow-up. METHODS: An interventional case series. RESULTS: A 62-year-old man with choroidal melanoma in his left eye was treated with endoresection with pars plana vitrectomy followed by radioactive ruthenium plaque radiotherapy. Thirteen months after the surgery, the patient developed a CNVM at the superior edge of the surgical excision site and was treated with argon laser photocoagulation. Twenty-eight months after laser photocoagulation, the patient was alive with no sign of CNVM recurrence. A 59-year-old man with choroidal melanoma in his left eye underwent endoresection with pars plana vitrectomy followed by radioactive ruthenium plaque radiotherapy. Twenty-one months later, he developed a CNVM, which was treated by photodynamic therapy. After 45 months of follow-up after photodynamic therapy, the patient had no sign of recurrent CNVM. CONCLUSION: Choroidal neovascular membrane is a rare complication after endoresection of choroidal melanoma. Being aware of this risk leads to early diagnosis and prompt treatment that can prevent deterioration of vision.

Cyclo-oxygenase-2 expression in photon-radiated and non-radiated uveal melanomas.

PURPOSE: To determine and compare cyclo-oxygenase-2 (COX-2) expression in photon-radiated and non-radiated malignant uveal melanomas and to analyse the correlation between COX-2 expression and prognosis. METHODS: Immunohistochemical staining for COX-2 was performed on 21 uveal melanomas that were endoresected after prior stereotactic radiotherapy with photons and on 22 tumours that were treated by endoresection without prior radiotherapy. COX-2 staining was further analysed in respect to cell type, maximal prominence, time interval between radiotherapy and surgery, apoptotic index (AI), proliferative index (PI) and the development of metastatic disease. RESULTS: There was no difference in COX-2 expression between radiated and non-radiated melanomas (P>0.15). COX-2 staining correlated with neither the tumour prominence (P>0.40) nor the AI or the PI (both P>0.35). Tumours with high COX-2 expression were significantly more likely to develop metastasis (P=0.022). CONCLUSION: Radiotherapy with photons does not induce COX-2 expression in malignant melanomas of the uvea. But high COX-2 expression may be a marker for poor prognosis.

Choroidal neovascularisation after surgical removal of submacular lipid plaques in diabetic maculopathy.

BACKGROUND: We report a case of choroidal neovascularisation (CNV) that developed after surgical removal of submacular lipid plaques secondary to diabetic maculopathy. METHODS: A 73-year-old man with diabetic maculopathy underwent standard pars plana vitrectomy and surgical removal of the submacular lipid plaques. RESULTS: Preoperative visual acuity was 20/200. Funduscopy revealed a macular oedema and subretinal lipid plaques at the macula. Nine months after surgery visual acuity had dropped to 20/320 and subfoveal CNV was diagnosed by fluorescein angiography. Observational management was chosen. At the last examination, 27 months after surgery, visual acuity had worsened to 20/500 and a CNV scar was seen at the macula. CONCLUSIONS: CNV development should be kept in mind as a possible complication of surgical removal of submacular lipid plaques in patients with diabetic retinopathy.