Enken Gundlach

Interleukin-2 Receptor and Angiotensin-Converting Enzyme as Markers for Ocular Sarcoidosis.

Purpose To study the impact of soluble IL2 receptor (sIL2R), chest x-ray (CxR), and angiotensin-converting enzyme (ACE) as markers for sarcoidosis in uveitis patients. Design Retrospective study. Methods Serum concentrations of sIL2R and ACE were measured in patients with active uveitis. Those with elevated sIL2R and /or ACE values were examined for suspected systemic sarcoidosis. Main Outcome Measure Our main outcome parameters were the specificity and sensitivity of sIL2R, CxR and ACE in screening for ocular sarcoidosis. Results We measured 261 patients with uveitis for sarcoidosis using sIL2R and ACE between January 2008 and November 2011; sarcoidosis was been diagnosed using other tests (e.g. computer tomography, brochoalveolar lavage, biopsy) in 41 of 53 patients with elevated sIL2R values (>639 U/ml) and in one patient with normal sIL2R (582 U/ml). Their mean sIL2R value was 1310 U/ml, extending from 582 to 8659 U/ml. Only 9 patients, however, presented elevated ACE (>82 U/l). Their mean ACE value was 116.4 U/l, ranging from 84.1 to 175.5 U/l. IL2R specificity was 94% with 98% sensitivity. In contrast, ACE had a specificity of 99.5%, but a sensitivity of only 22%; the chest x-ray had a specificity of 100% with 50% sensitivity in detecting sarcoidosis. We observed the entire spectrum of uveitis: sixteen patients suffered from anterior, 8 from intermediate, 16 from posterior, and 2 from panuveitis. Conclusions An elevated level of soluble IL2R suggests sarcoidosis with uveitis more convincingly than ACE, making sIL2R a more effective marker parameter for sarcoidosis than ACE or chest x-ray in uveitis patients.

Superior Versus Temporal Approach in Descemet Membrane Endothelial Keratoplasty

PURPOSE To compare superior vs temporal approach in patients who underwent Descemet membrane endothelial keratoplasty (DMEK). DESIGN Monocentric, prospective nonmasked study. METHODS A prospective analysis of 53 DMEKs between January and September 2013 was performed at the Charité-Universitätsmedizin Berlin. Only DMEK cases with an incision size of 2.3 mm and with at least 1 month of follow-up were included. The surgically induced astigmatism (SIA), changes in corneal aberrations and in spherical equivalent, visual acuity, endothelial cell density, and complications were evaluated. RESULTS Visual acuity improved significantly (0.70 ± 0.39 logMAR vs 0.32 ± 0.31 logMAR after 1 month (n = 48), 0.19 ± 0.15 logMAR after 3 months (n = 46), and 0.16 ± 0.17 logMAR after 6 months (n = 47) (P < .001)) regardless of the approach. SIA was significantly lower after temporal than after superior approach (1.42 ± 0.91 diopters [D] [n = 13] vs 0.81 ± 0.68 D [n = 13], P = .038). Change in total root mean square of all aberrations (RMS) (P = .046) at 6 mm pupil diameter, and change in total RMS (P = .019), third-order aberrations (P = .007), and fourth-order aberrations (P = .041) at 4 mm pupil diameter, demonstrated significantly lower results after temporal compared to superior approach. A higher rate of eyes after temporal approach underwent at least 1 rebubbling (39.1% vs 26.7%, P = .252). The endothelial cell density (P = .053) and the change in spherical equivalent (P = .145) did not differ significantly. CONCLUSIONS The temporal approach induces significantly less SIA and corneal aberration. There are no significant differences between superior and temporal approach according to the change in spherical equivalent, visual acuity, and endothelial cell density. The need for rebubbling is higher using the temporal approach.

Fellow Eye Comparison of Descemet Membrane Endothelial Keratoplasty and Penetrating Keratoplasty.

Purpose: To compare the visual outcomes and postoperative complications in patients undergoing penetrating keratoplasty (PKP) in 1 eye followed by Descemet membrane endothelial keratoplasty (DMEK) in their fellow eye. Methods: A retrospective analysis of 11 patients, who underwent a PKP procedure first in 1 eye and then a DMEK surgery in their fellow eye, was performed. Intraoperative and postoperative complications were recorded. Visual and refractive outcomes were also evaluated, including higher-order aberrations (HOAs) and contrast thresholds. A subjective questionnaire was used to evaluate patient satisfaction. Results: Both uncorrected and best-corrected visual acuities were significantly better in the case of DMEK when compared with that in the case of PKP (0.82 vs. 0.37 logMAR, P = 0.005; 0.61 vs. 0.21 logMAR, P = 0.011, respectively). Postkeratoplasty astigmatism, mean spherical equivalent, and HOAs were also significantly lower in eyes after undergoing DMEK than after undergoing PKP (3.90 vs. 0.89 diopters, P = 0.005; −3.90 vs. −0.68 diopters, P = 0.005; 6.81 vs. 1.71 µm, P = 0.043, respectively). Visual outcome and patient satisfaction were significantly better in those who underwent DMEK (2.91 vs. 4.45, P = 0.011; 3.27 vs. 5.64, P = 0.016, respectively). The estimated time for recovery and rehabilitation was significantly shorter after DMEK (64.0 vs. 9.3 days, P = 0.012). Contrast threshold was better after the DMEK. Ten of 11 patients preferred DMEK procedure. Conclusions: The Patients preferred DMEK to PKP. The reasons for better patient satisfaction after DMEK included better uncorrected visual acuity, better best-corrected visual acuity, avoidance of surgery-induced astigmatism, and lower HOA.

Franceschetti hereditary recurrent corneal erosion.

PURPOSE To describe new affected individuals of Franceschettis original pedigree of hereditary recurrent erosion and to classify a unique entity called Franceschetti corneal dystrophy. DESIGN Observational case series. METHODS Slit-lamp examination of 10 affected individuals was conducted. Biomicroscopic examinations were supplemented by peripheral corneal biopsy in 1 affected patient with corneal haze. Tissue was processed for light and electron microscopy and immunohistochemistry was performed. DNA analysis was carried out in 12 affected and 3 nonaffected family members. RESULTS All affected individuals suffered from severe ocular pain in the first decade of life, attributable to recurrent corneal erosions. Six adult patients developed bilateral diffuse subepithelial opacifications in the central and paracentral cornea. The remaining 4 affected individuals had clear corneas in the pain-free stage of the disorder. Histologic and immunohistochemical examination of the peripheral cornea in a single patient showed a subepithelial, avascular pannus. There was negative staining with Congo red. DNA analysis excluded mutations in the transforming growth factor beta-induced (TGFBI) gene and in the tumor-associated calcium signal transducer 2 (TACSTD2) gene. CONCLUSION We have extended the pedigree of Franceschetti corneal dystrophy and elaborated its natural history on the basis of clinical examinations. A distinctive feature is the appearance of subepithelial opacities in adult life, accompanied by a decreased frequency of recurrent erosion attacks. Its clinical features appear to distinguish it from most other forms of dominantly inherited recurrent corneal erosion reported in the literature.

Salvage proton beam therapy in local recurrent uveal melanoma.

PURPOSE To evaluate survival and ocular outcome in recurrent uveal melanoma treated with proton beam therapy as salvage therapy. DESIGN Retrospective, interventional case series. METHODS We evaluated 48 patients with local recurrence of uveal melanoma after primary treatment with brachytherapy, transpupillary thermotherapy, proton beam therapy, laser photocoagulation, CyberKnife radiation, or photodynamic therapy. All patients received proton beam therapy as a salvage therapy at the Helmholtz Zentrum Berlin between July 2000 and December 2010. Kaplan-Meier analysis was used to obtain survival rates. RESULTS The Kaplan-Meier estimator for local tumor control was 92.1% at 10 years after secondary treatment with proton beam therapy. Local recurrence developed in 3 patients; 1 of them underwent enucleation. During follow-up, 20.8% of the patients died (16.7% of metastasis, 4.1% of other causes or not specified). The most frequent surgical interventions were phacoemulsification (20.8%) and pars plana vitrectomy (10.4%). The Kaplan-Meier estimators were 77.4% for survival and 70.1% for the absence of metastasis 10 years after the primary treatment. CONCLUSIONS Proton beam therapy as a salvage treatment resulted in high local tumor control rates in recurrent uveal melanoma, especially if the primary therapy was transpupillary thermotherapy or plaque brachytherapy. Preservation of the globe was possible in most patients. Enucleations were indicated only in case of re-recurrences of uveal melanoma, but not because of secondary complications like intractable pain or secondary glaucoma. Retreatment was associated with vision deterioration, but loss of vision remained exceptional. Further larger prospective studies are needed to confirm the presented results of our retrospective analysis.

B-Raf inhibition in conjunctival melanoma cell lines with PLX 4720.

Purpose Mutations in the gene coding for the kinase B-Raf are associated with tumour growth in conjunctival melanoma. The purpose of this study is to explore effects of pharmacological B-Raf inhibition in conjunctival melanoma cell lines. Methods The B-Raf genotypes were assessed by PCR and subsequent sequencing. Cytotoxicity, cell viability, proliferation, apoptosis rate and phosphorylation rate of ERK and Akt were analysed in three different conjunctival melanoma cell lines under the influence of the B-Raf inhibitor PLX 4720 at various concentrations. Results The cell lines CRMM-1 and CM2005.1 showed the B-Raf V600E mutation, whereas CRMM-2 expressed a B-Raf wild type. CM2005.1 was highly sensitive to PLX 4720, showing a complete cytotoxic effect for >1 µM, as well as a significant concentration-dependent reduction of the proliferation rate and viability rate. Even though CRMM-1 also carries the B-Raf V600E mutation, it did not react as sensitive to PLX 4720 inhibition as CM2005.1, but showed a significant concentration-dependent reduction regarding proliferation and viability. PLX 4720 had only slight impact on CRMM-2 in high concentrations (10 µM) regarding cytotoxicity, proliferation and viability. Fluorescence-activated cell sorting analysis revealed that PLX 4720 acted predominantly antiproliferative and not via an induction of apoptosis. The phosphorylation rate of ERK was significantly reduced in CRMM-1 and CM2005.1, while it remained unchanged in CRMM-2. The phosphorylation rate of Akt was significantly elevated in CRMM-2. Conclusions Proliferation inhibition of conjunctival melanoma cells by PLX 4720 depends on their B-Raf genotype. Therefore, therapeutic application of B-Raf inhibitors should take into account the specific B-Raf genotype.

Rate and Localization of Graft Detachment in Descemet Membrane Endothelial Keratoplasty.

Purpose: To investigate the rate and localization of graft detachment after Descemet membrane endothelial keratoplasty. Methods: Sixty-six consecutive cases operated between June and August 2014 at the Charité–Universitätsmedizin Berlin were examined prospectively 1 week postoperatively. A single masked observer analyzed the rate and localization of graft detachment using optical coherence tomography (OCT), and the rebubbling rate was measured. Localization of graft detachment was correlated to the incision approach. Preoperative data were correlated to the rate of graft detachment and rebubbling. Results: Graft detachment occurred in more than 2 clock hours and with postoperative corneal edema in 33.3% and required rebubbling. In 33.3%, graft detachment occurred in more than 2 clock hours and with postoperative corneal edema and required rebubbling. The mean graft detachment rate was 8.3% per clock hour. A significantly higher graft detachment rate was noted in the inferior clock hours (21.1%, P < 0.0001, 16.7%, P = 0.003). Only higher age of the patient correlated to a higher rate of graft detachment (P = 0.022). No correlation was found between localization of graft detachment and the incision approach (P = 0.615). Conclusions: The graft detachment rate is high after Descemet membrane endothelial keratoplasty, but detachment is usually peripheral, partial and mainly inferior and involves only a few clock hours. Only higher age of the patient is strongly associated with a higher rate of graft detachment. The incision approach is not significantly correlated with the localization of graft detachment. Therefore, the postoperative supine position of the patient seems to be of major importance. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02020044.

Descemet Membrane Endothelial Keratoplasty for Graft Failure After Descemet Stripping Endothelial Keratoplasty: Clinical Results and Histopathologic Findings

IMPORTANCE The management of graft failure is increasingly relevant with the spread and growing acceptance of endothelial keratoplasty. OBJECTIVES To investigate the functional and anatomical results of secondary Descemet membrane endothelial keratoplasty (DMEK) for graft failure after Descemet stripping endothelial keratoplasty (DSEK) and to histologically analyze the stroma-to-stroma interface with respect to clinical implications. DESIGN, SETTING, AND PARTICIPANTS In a single-surgeon prospective comparative case series at the Department of Ophthalmology, Charité-University Medicine Berlin, Berlin, Germany, 8 eyes (3.8%) of 210 consecutively performed DMEK procedures underwent a secondary DMEK for graft failure after DSEK from March 1, 2012, through February 28, 2013. Those cases were compared with the eyes of a reference collective (n = 30) and matched-pairs group (n = 8) after primary DMEK for Fuchs endothelial dystrophy. INTERVENTION Descemet membrane endothelial keratoplasty. MAIN OUTCOMES AND MEASURES Postoperative best-corrected visual acuity (BCVA) and central corneal thickness at 1, 3, 6, and 12 months. Intraoperatively obtained DSEK graft lenticels were investigated immunohistochemically. RESULTS Patients with graft failure after DSEK had a mean (SD) age of 79.4 (7.2) years (range, 70-90 years). Preoperatively, the mean (SD) BCVA was 1.13 (0.50) logMAR (20/250 Snellen equivalents), and the mean (SD) central corneal thickness measured 704 (161) µm. Twelve months postoperatively, the mean (SD) corneal thickness decreased to 524 (27) µm after secondary and 516 (27) µm after primary DMEK (P = .57). A mean (SD) BCVA of 0.38 (0.36) logMAR (20/50 Snellen equivalents) was achieved after secondary DMEK compared with 0.15 (0.15) logMAR (20/28 Snellen equivalents) after primary DMEK. Histologically, failed DSEK graft lenticels presented condensations of collagen layers. Fibronectin and cytokeratin were accumulated along the stroma-to-stroma interface; vimentin was found in loosened graft stroma. CONCLUSIONS AND RELEVANCE These data suggest that DMEK might be considered a feasible choice in patients with graft failure after DSEK. However, the visual restitution might be impeded because of preceded depositions of matrix proteins within the corneal stroma and the stroma-to-stroma interface, which are associated with corneal fibrosis. Thereby, fibrotic processes might be avoided by performing a secondary DMEK in an early phase of graft failure.

Diagnostics and treatment of primary vitreoretinal lymphoma

ZusammenfassungHintergrundBeim primären vitreoretinalen Lymphom (PVRL), einem seltenen hämatopoetischen okulären Tumor, handelt es sich meist um ein großzelliges diffuses B-Zell-Lymphom. Das PVRL, das früher auch als primäres intraokulares Lymphom (PIOL) bezeichnet wurde, ist eine Unterart des primären ZNS-Lymphoms (PZNSL). DiagnostikDie Diagnose gestaltet sich häufig sehr schwierig, da klinisch eine intermediäre bzw. posteriore Uveitis imitiert wird. Dies wird auch als sog. „Masquerade-Syndrom“ bezeichnet. Notwendig für die endgültige Diagnose sind immunhistochemische, zytologische, pathologische und auch molekularpathologische Untersuchungen der operativ gewonnenen okulären Gewebe. Als hilfreich hat sich auch die Zytokinbestimmung (Interleukin-10) entweder im Vorderkammerpunktat oder im Glaskörpergewebe erwiesen. TherapieLeider zeigen sich die Therapien, die erfolgreich in der Behandlung der systemischen Lymphome sind, weniger effektiv in der Therapie des PVRLs und des PZNSLs. Daher werden heutzutage beim PVRL, zeitweise in Kombination mit einer Radiatio, aggressive chemotherapeutische Substanzen wie Methotrexat und Rituximab appliziert. Hierbei werden beide Chemotherapeutika sowohl systemisch als auch lokal verabreicht. Lediglich beim monokularen PVRL wird die alleinige intravitreale Gabe einer dieser Substanzen diskutiert. Bisher herrscht noch Uneinigkeit, ob die lokale Monotherapie ausreichend ist. Das PVRL reagiert meist sehr gut auf die initiale Therapie, jedoch kommt es im Verlauf häufig zu Rezidiven wie auch zum Auftreten einer ZNS-Manifestation, welche die Prognose quoad vitam deutlich limitieren.AbstractBackgroundPrimary vitreoretinal lymphoma (PVRL) is a rare ocular lymphoid malignancy, mostly a diffuse large B-cell lymphoma. The PVRL, previously called primary intraocular lymphoma (PIOL), is a subset of primary central nervous system lymphoma (PCNSL). DiagnosisThe diagnosis of PVRL is often difficult as it often mimics chronic intermediate or posterior uveitis; therefore, PVRL requires various procedures for the diagnostics, e.g. immunohistochemistry, cytology, pathology, molecular pathology and cytokine analysis (interleukin 10) after surgically obtaining ocular specimens.TherapyTreatment forms that are effective for systemic lymphomas have not been reliably successful for PVRL and PCNSL. Current management of PVRL consists of chemotherapy, such as methotrexate or rituximab, possibly combined with external beam radiation whereby both chemotherapeutic agents are administered systemically as well as intravitreally. Intravitreal treatment alone is recommended solely in the case of monocular PVRL, which is highly controversial. A PVRL usually responds well to initial treatment; however, relapse rates and CNS involvement are high, resulting in a poor prognosis and limited survival.

Diagnostik und Therapie des primären vitreoretinalen Lymphoms

ZusammenfassungHintergrundBeim primären vitreoretinalen Lymphom (PVRL), einem seltenen hämatopoetischen okulären Tumor, handelt es sich meist um ein großzelliges diffuses B-Zell-Lymphom. Das PVRL, das früher auch als primäres intraokulares Lymphom (PIOL) bezeichnet wurde, ist eine Unterart des primären ZNS-Lymphoms (PZNSL). DiagnostikDie Diagnose gestaltet sich häufig sehr schwierig, da klinisch eine intermediäre bzw. posteriore Uveitis imitiert wird. Dies wird auch als sog. „Masquerade-Syndrom“ bezeichnet. Notwendig für die endgültige Diagnose sind immunhistochemische, zytologische, pathologische und auch molekularpathologische Untersuchungen der operativ gewonnenen okulären Gewebe. Als hilfreich hat sich auch die Zytokinbestimmung (Interleukin-10) entweder im Vorderkammerpunktat oder im Glaskörpergewebe erwiesen. TherapieLeider zeigen sich die Therapien, die erfolgreich in der Behandlung der systemischen Lymphome sind, weniger effektiv in der Therapie des PVRLs und des PZNSLs. Daher werden heutzutage beim PVRL, zeitweise in Kombination mit einer Radiatio, aggressive chemotherapeutische Substanzen wie Methotrexat und Rituximab appliziert. Hierbei werden beide Chemotherapeutika sowohl systemisch als auch lokal verabreicht. Lediglich beim monokularen PVRL wird die alleinige intravitreale Gabe einer dieser Substanzen diskutiert. Bisher herrscht noch Uneinigkeit, ob die lokale Monotherapie ausreichend ist. Das PVRL reagiert meist sehr gut auf die initiale Therapie, jedoch kommt es im Verlauf häufig zu Rezidiven wie auch zum Auftreten einer ZNS-Manifestation, welche die Prognose quoad vitam deutlich limitieren.AbstractBackgroundPrimary vitreoretinal lymphoma (PVRL) is a rare ocular lymphoid malignancy, mostly a diffuse large B-cell lymphoma. The PVRL, previously called primary intraocular lymphoma (PIOL), is a subset of primary central nervous system lymphoma (PCNSL). DiagnosisThe diagnosis of PVRL is often difficult as it often mimics chronic intermediate or posterior uveitis; therefore, PVRL requires various procedures for the diagnostics, e.g. immunohistochemistry, cytology, pathology, molecular pathology and cytokine analysis (interleukin 10) after surgically obtaining ocular specimens.TherapyTreatment forms that are effective for systemic lymphomas have not been reliably successful for PVRL and PCNSL. Current management of PVRL consists of chemotherapy, such as methotrexate or rituximab, possibly combined with external beam radiation whereby both chemotherapeutic agents are administered systemically as well as intravitreally. Intravitreal treatment alone is recommended solely in the case of monocular PVRL, which is highly controversial. A PVRL usually responds well to initial treatment; however, relapse rates and CNS involvement are high, resulting in a poor prognosis and limited survival.