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Purpose To evaluate the outcome of Descemet Membrane Endothelial Keratoplasty (DMEK) in eyes with pre-existing glaucoma. Design In this retrospective, observational case series we included data of 150 consecutive DMEKs in eyes with pre-existing glaucoma of 150 patients after excluding data of the second treated eye of each patient and of re-DMEKs during follow-up. Cumulative incidences of IOP elevation (IOP > 21 mmHg or ≥ 10 mmHg increase in IOP from preoperative value), post-DMEK glaucoma (need of an additional intervention due to worsening of the IOP), graft rejection, and graft failure rate were analyzed using Kaplan–Meier survival analysis. COX regression analysis was used to evaluate independent risk factors. Results The 36-month cumulative incidence of IOP elevation was 53.5% [95 CI 43.5–63.5%] and of post-DMEK glaucoma 36.3% [95 CI 26.3–46.3%]. Graft rejection occurred with a 36-month cumulative incidence of 9.2% [CI 95% 2.3–16.1]. None of the analyzed risk factors increased the risk for the development of graft rejection. The 36-month cumulative incidence of graft failure was 16.6% [CI 95% 8.4–24.8]. Independent risk factors for graft failure were the indication for DMEK “status after graft failure” (n = 16) compared to Fuchs’ dystrophy (n = 74) (p = 0.045, HR 8.511 [CI 95% 1.054–68.756]) and pre-existing filtrating surgery via glaucoma drainage device (GDD) (n = 10) compared to no surgery/iridectomy (n = 109) (p = 0.014, HR 6.273 [CI 95% 1.456–27.031]). Conclusion The risks of postoperative complications (IOP elevation, post-DMEK glaucoma, graft rejection, and graft failure) in patients with pre-existing glaucoma are high. In particular, pre-existing filtrating surgery via GDD implantation—but not trabeculectomy—and DMEK after graft failure increase the risk of graft failure.

PURPOSE To study the change in contrast sensitivities in eyes with Fuchs endothelial dystrophy and bullous keratopathy after Descemet membrane endothelial keratoplasty (DMEK). METHODS In this prospective study, 50 pseudophakic eyes of 50 patients who received DMEK surgery at the Charite-Universitatsmedizin Berlin were included. Visual acuity; contrast sensitivity using OPTEC 6500 at spatial frequencies of 1.5, 3, 6, 12, and 18 cycles/degree in photopic and mesopic light with and without glare; central corneal thickness (CCT); and anterior and posterior corneal aberrations were measured preoperatively and at 3 and 12 months postoperatively. RESULTS Best-corrected visual acuity (preoperative 0.67 ± 0.46 and after 12 months 0.19 ± 0.16 LogMAR, P < 0.001) and photopic and mesopic contrast sensitivities with and without glare improved significantly, whereas CCT decreased significantly (preoperative 677 ± 114 μm, after 12 months 527 ± 29 μm, P < 0.001). Preoperative CCT correlates significantly with preoperative photopic contrast sensitivity (correlation coefficient -0.462, P = 0.002), and postoperative total anterior aberrations correlates with postoperative photopic contrast sensitivity (correlation coefficient -0.361, P = 0.006). CONCLUSIONS Photopic and mesopic contrast sensitivities, especially with glare, are impaired in patients with Fuchs endothelial dystrophy and bullous keratopathy. The extent of the corneal thickening seems to mainly influence the contrast sensitivity preoperatively. DMEK surgery improves the contrast sensitivity significantly. However, higher postoperative anterior corneal aberrations limit the postoperative contrast sensitivities.

Purpose/Aim of the study: Graft detachment after DMEK can be treated easily with an additional air injection – re-bubbling. The aim of our study was to investigate the effect of a re-bubbling on th...

Unfolding and attachment of the posterior donor lamella may be the most challenging part in Descemet membrane endothelial keratoplasty (DMEK) procedure. We investigated the correlation of the difficulty degrees of this step to the postoperative clinical outcome 6 years after surgery. One hundred sixty-nine consecutive DMEKs between September 2012 and August 2013 at the Charite–University Medicine Berlin were graded prospectively into 4 groups according to their grade of difficulty in unfolding and attachment of the graft lamella. Postoperative visual acuity, endothelial cell density, and rate of graft failure were measured after 1 year, after 2 years, and after 6 years and analyzed according to their grading group. Visual acuity improved significantly in all groups and did not differ significantly between the grading groups at any time point postoperatively. There was a significant decrease of endothelial cell density in all groups with a significantly higher endothelial cell loss in group IV compared with the other groups within the first 24 months after surgery. The graft failure rate was significantly higher in eyes graded III and IV than in groups I and II (p = 0.012). Although the endothelial cell loss and the graft failure rate increase significantly with a more difficult graft unfolding and attachment, DMEK surgery is a promising procedure with a good long-term postoperative outcome. A direct manipulation of the graft lamella for unfolding and centering by cannula or forceps should be avoided if possible to reduce the risk of an increased endothelial cell loss and a higher graft failure rate. NCT02020044

PURPOSE Intraocular pressure (IOP) elevation occurs regularly after Descemet membrane endothelial keratoplasty (DMEK). This study evaluated the long-term incidence of IOP elevation and post-DMEK glaucoma after DMEK. METHODS A total of 463 consecutive DMEKs in 352 patients performed between September 2011 and September 2014 at the Universitatsmedizin-Charite Berlin were reviewed. Data of the second treated eye of each patient and of re-DMEKs during the follow-up were excluded. The 12- and 36-month incidence of IOP elevation and post-DMEK glaucoma was analyzed using the Kaplan-Meier survival analysis. IOP elevation was defined as IOP ≥22 mm Hg or ≥10 mm Hg from preoperative baseline. COX regression analysis was used to evaluate the risk factors for IOP elevation and the development of a post-DMEK glaucoma. RESULTS The 12-month incidence of IOP elevation was 15.9% [95 confidence interval (CI), 12.0%-19.8%] and that of post-DMEK glaucoma was 3.9% (95 CI, 1.7%-6.1%); the 36-month incidence was 18.8% (95 CI, 14.5%-23.1%) and that of post-DMEK glaucoma was 6.6% (95 CI, 3.7%-9.5%). The most frequent cause was steroid-induced IOP elevation with a 12-month incidence of 11.7% (95 CI, 8.2%-15.2%) and a 36-month incidence of 12.9% (95 CI, 9.2%-16.6%), respectively. The incidence of postoperative pupillary block IOP elevation was 7.5% (95 CI, 4.8%-10.2%). A preexisting glaucoma increased the risk of IOP elevation [P < 0.001, hazard ratio (HR) 3.331; 95% CI, 1.919-5.782] and the development of a post-DMEK glaucoma (P < 0.001, HR 6.633; 95% CI, 2.556-17.215). The preoperative diagnosis also influenced the risk of IOP elevation [Fuchs corneal dystrophy (FED) vs. bullous keratopathy; P = 0.012, HR 2.354; 95% CI, 1.203-4.608] and post-DMEK glaucoma (FED vs. graft failure; P = 0.01, HR 4.412; 95% CI, 1.419-13.723, FED vs. bullous keratopathy; P = 0.09, HR 2.679; 95% CI, 0.858-8.358). CONCLUSIONS Incidence of IOP elevation is high in the first 12 months after DMEK, especially steroid-induced IOP elevation. Steroid-induced IOP elevation could be treated effectively by tapering down the steroid medication or changing the steroid drug. A preexisting glaucoma and the preoperative diagnosis increase the risk for an IOP elevation and a post-DMEK glaucoma.

Sarcoidosis is a multisystem disorder of unknown cause. Ophthalmic involvement occurs in up to 60% of all patients, often as the first manifestation of sarcoidosis. Because of the heterogeneous clinical presentation diagnosis can be difficult; therefore the International Workshop on Ocular Sarcoidosis (IWOS 2009) diagnostic criteria based on clinical presentation, laboratory investigations and imaging techniques enable establishment of the diagnosis. Patients suffering from sarcoidosis should be treated by both ophthalmologists and internal physicians. Corticosteroids are commonly used for treatment, although in some patients the therapy has to be escalated by further immunosuppressants. Finally, a good cooperation between ophthalmologists and internal physicians results in a mostly good prognosis.

To analyze the risk factors for the development of neovascular glaucoma (NVG) of patients with choroidal melanoma after proton beam therapy (PBT).Clinical case series, retrospective study. We evaluated 629 consecutive patients receiving proton beam therapy for the treatment of a choroidal melanoma at the oncology service at Charité, Berlin and Helmholtz-Zentrum, Berlin between 05/1998 and 11/2008 regarding the development and risk factors of NVG. Patients with tumor resection, salvage proton beam therapy for recurrent disease and known glaucoma of other origin were excluded from the cohort.Of the 629 patients matching the inclusion criteria, 20.8% developed neovascularization of the iris after a mean time of 2.0 years (range 0.45 to 8.4 years) after PBT. Forty-seven percent of the patients with a neovascularization of the iris developed NVG after a mean time of 2.0 years after PBT, ranging from 5 months to 11.6 years. Univariate analysis revealed tumor height [p 0.001, hazard ratio (HR): 2.71, 95% confidence interval (CI): 1.36-5.35 for tumors6 mm ≤9 mm and 11.32 (4.03-31.73) for tumors9 mm], distance of the tumor to the optic disc (p 0.001, HR: 0.43, 95% CI: 0.24-0.77 for0 mm ≤3 mm and HR: 0.13, 95% CI: 0.04-0.37 for3 mm), dose to the ciliary body (p 0.001, HR: 9.21, 95% CI: 5.08-16.71 (21-40 cobalt gray equivalents (CGE), HR 27.23, 95% CI: 6.33-116.97 (41-60 CGE)), dose to the optic disc (p 0.001, HR: 3.53, 95% CI: 1.11-11.27 (21-40CGE), HR: 5.37, 95% CI: 2.72-10.63 (41-60CGE)), the irradiated length of the optic nerve (p 0.001, HR: 4.48, 95% CI: 2.47-8.13) and diabetes mellitus (p 0.05, HR: 2.53, 95% CI: 1.4-4.5) were found to be risk factors for the development of NVG. Multivariate regression analysis identified the dose to the ciliary body [p 0.001, HR: 4.39, 95% CI: 2.28-8.44 (21-40 CGE), HR: 11.04, 95% CI: 1.97-61.69 (41-60 CGE)], the irradiated length of the optic nerve (p 0.001, HR: 3.88, 95% CI: 2.11-7.16), the existence of diabetes mellitus (p 0.01, HR: 1.28, 95% CI: 1.24-4.21) and tumor height [p 0.05, HR: 2.28, 95% CI: 1.17-4.83 (6 mm ≤9 mm), HR: 3.74, 95% CI: 1.05-13.23, (9 mm)] to be independent risk factors for the development of NVG.In the present analysis we found tumor height, dose to the ciliary body, irradiated length of the optic nerve and diabetes mellitus to be risk factors for the development of NVG. Whenever possible, critical structures of the anterior and posterior segment should be spared by beam shaping or changing of the beam entry angle.

Retrospective evaluation of intraocular pressure, use of topical and systemic anti-glaucoma medication, secondary complications, local tumor control and survival in patients treated with trabeculectomy for the regulation of the intraocular pressure (IOP) after proton beam therapy for uveal melanoma. In this retrospective clinical case series we evaluated the follow-up of 15 patients receiving a trabeculectomy as surgical treatment if the IOP could not be lowered adequately by medications or laser surgery. All patients had received proton beam therapy for uveal melanoma at the Helmholtz-Zentrum Berlin between 1998 and 2010. The median IOP decreased significantly from 35 mmHg ± 8.8 before TE to 16 mmHg ± 8.2 (=52.3 %) six months after TE (Wilcoxon-Mann–Whitney-U Test, p

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 Charite-Universitatsmedizin 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.

Pseudophakic cystoid macular edema (PCME) remains the most common cause of poor visual outcome following cataract surgery. Whereas acute PCME may resolve itself spontaneously, some patients will suffer from vision impairment and will be difficult to treat. Although PCME has already been described approximately 50 years ago, its pathophysiology remains uncertain and a multitude of mechanisms have been suggested. As broad as the mechanisms, as many are the treatment options. Topical nonsteroidal anti-inflammatory agents (NSAIDs) and corticosteroids either as mono- or combined therapy are a commonly used first line approach. When ineffective, systemic treatment with these agents may be an option. Alternatively, intravitreal application of corticosteroids and anti-vascular endothelial growth factor (anti-VEGF) may offer an effective option, if first-line treatment fails. A critical evaluation of the current literature revealed that the optimal treatment of PCME remains unclear and requires further investigation. In addition, prevention should be of foremost importance and remains an open issue. Identification of risk factors, application of NSAIDs and consequent follow-up are potential essential steps in the avoidance of this complication.

Hintergrund Beim primaren vitreoretinalen Lymphom (PVRL), einem seltenen hamatopoetischen okularen Tumor, handelt es sich meist um ein groszelliges diffuses B-Zell-Lymphom. Das PVRL, das fruher auch als primares intraokulares Lymphom (PIOL) bezeichnet wurde, ist eine Unterart des primaren ZNS-Lymphoms (PZNSL).

To investigate outcome and postoperative complications in patients undergoing isolated DMEK in phakic eyes compared to patients undergoing DMEK combined with cataract surgery (triple procedure).A retrospective analysis of 13 eyes undergoing DMEK in phakic eyes and 54 eyes undergoing triple procedure. Intraoperative and postoperative complications were recorded, visual acuity, refraction outcome, central corneal thickness, endothelial cell count and optical coherence tomography (OCT) of the anterior eye segment were evaluated 6 months postoperatively.Graft detachment occurred in two eyes (18 %) undergoing phakic DMEK surgery and 23 eyes (50 %) undergoing triple procedure. Two eyes of the phakic group needed subsequent cataract surgery. In all cases, visual acuity significantly increased with a medium visual acuity of 0.13 ± 0.12 (phakic group, p = 0.005) and 0.15 ± 0.11 (triple group, p 0.001) logMAR. Visual acuity of at least 0.1 logMAR was found in 55 % (phakic group) and 52 % (triple procedure group) of eyes. In the group after triple procedure, there were 62.8 % of eyes within 1 D of emmetropia. Corneal thickness was reduced to 515.3 ± 36.9 μm (phakic group, p = 0.012) and 516.5 ± 40.4 μm (triple group, p 0.001). Endothelial cell count was reduced to 1529.7 ± 695.6/mm(2) (phakic group, p = 0.008) and 1,676.8 ± 355.2/mm(2) (triple group, p 0.001).DMEK in phakic eyes provides very good visual acuity with lower postoperative complications compared to eyes undergoing triple procedure. As the accommodative power can be preserved, this method is especially interesting for young patients.

Aims: The aim of this study was to correlate the ophthalmoscopic and histopathological findings of orange pigment overlying a choroidal metastasis. Methods: This is a single case report with clinical follow-up and histopathological examination. Results: Histopathology revealed a choroidal metastasis with subretinal CD68-positive macrophages showing autofluorescent deposits in fluorescence microscopy. Conclusion: The development of orange pigment is not pathognomonic for choroidal melanoma but may be seen in other lesions such as carcinoma metastasis.

In this retrospective study, the visual outcomes and postoperative complications after Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) in the fellow eye were compared. The patient's satisfaction was evaluated.A retrospective analysis of 10 patients, who underwent DSAEK in one eye and DMEK surgery in their fellow eye, was performed. Intraoperative and postoperative complications were recorded. Visual and refractive outcomes were evaluated, including higher-order aberrations (HOA) and contrast thresholds. A subjective questionnaire was used to evaluate patient satisfaction.Best-corrected visual acuity (BCVA) was significantly better in DMEK when compared with DSAEK (0.16±0.10 vs 0.45±0.58 logMAR, P=0.043). Contrast threshold was significantly higher after DMEK than after DSAEK (0.49±0.23 vs 0.25±0.18, P=0.043). Post-keratoplasty astigmatism, mean spherical equivalent, and HOA did not differ. Nine out of ten patients preferred the DMEK procedure. Visual outcome (4.80±1.14 vs 4.50±1.58, P=0.257), surgery associated pain and burden (DMEK: 1.30±0.48 vs DSAEK: 1.30±0.48, P=1.0), estimated time for recovery and rehabilitation (27.6±54.0 vs 24.9±54.8 days, P=0.173), and mean patient satisfaction (5.40±0.84 vs 5.00±1.05, P=0.257) were evaluated equally.Patient satisfaction reached high, equal values after DMEK and after DSAEK. Nevertheless, patients preferred DMEK, if given a choice. Reasons for the preference may include better uncorrected and BCVA, and especially a better contrast sensitivity.

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.

PURPOSE Intraocular pressure (IOP) elevation occurs regularly after Descemet membrane endothelial keratoplasty (DMEK). This study evaluated the effect of central corneal thickness (CCT) on the IOP after DMEK. PATIENTS AND METHODS This prospective study recorded the IOP of 46 eyes from 46 patients preoperatively, and then 1 and 3 months after DMEK. IOP measurement was performed by noncontact pneumatic tonometry (NCT), iCare, Goldmann applanation tonometry (GAT), and dynamic contour tonometry (DCT). CCT was analyzed by anterior-segment optical coherence tomography. RESULTS Mean IOPs as measured by NCT, iCare, GAT, and DCT, respectively, were 14.3, 11.6, 12.7, and 16.0 mm Hg preoperatively; 13.1, 12.6, 12.7, and 16.0 mm Hg after 1 month; and 14.7, 14.5, 12.9, and 17.7 mm Hg after 3 months. There was a correlation of IOP measurements between GAT and NCT (P=0.119), GAT and iCare (P=0.892), and iCare and NCT (P=0.081) after 1 month and between iCare and NCT (P=0.702) after 3 months. Although GAT recorded approximately stable IOP values, NCT, iCare, and DCT tended to measure a higher IOP postoperatively than preoperatively. Preoperatively, correlations between IOP and CCT were not statistically significant for any measurement technique. After 3 months, the IOP measured by NCT and iCare correlated significantly with CCT (P=0.003, 0.041). CONCLUSIONS Correlation between the different measurement techniques was poor and showed a broad distribution of limits of agreement. Therefore, a change between the 4 techniques during follow-up is not recommended. Nevertheless, all techniques detected the IOP elevation during follow-up, requiring therapy.

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.

Hintergrund Ziel der vorliegenden Studie war es, den Einfluss der Spenderlamellendicke auf die Sehscharfenentwicklung nach hinterer lamellarer Keratoplastik („Descemet’s stripping automated endothelial keratoplasty“, DSAEK) zu untersuchen.

Background Patients with initially low visual acuity were excluded from the therapy approval studies for retinal vein occlusion. But up to 28 % of patients presenting with central retinal vein occlusion have a baseline BCVA of less than 34 ETDRS letters (0.1). The purpose of our study was to assess visual acuity and central retinal thickness in patients suffering from central retinal vein occlusion and low visual acuity (

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.

a-c) waterfall plots of the ETDRS letter change 1 to 5Â months after DEX implantation compared to baseline of the control group. (DOCX 48 kb)

a-c) waterfall plots of the ETDRS letter change 1 to 5Â months after DEX implantation compared to baseline of the low VA group. (DOCX 48 kb)

To investigate visual outcome and postoperative complications in patients undergoing Descemet membrane endothelial keratoplasty with graft failure after penetrating keratoplasty.A retrospective analysis was performed with 5 patients who underwent Descemet membrane endothelial keratoplasty after failed penetrating keratoplasty. Intraoperative and postoperative complications were recorded. Visual acuity, rehabilitation phase, refraction stability, central corneal thickness, endothelial cell count, possible immunologic reactions, and optical coherence tomography of the anterior eye segment were evaluated. A subjective questionnaire was used to evaluate patient satisfaction.There were no intraoperative complications. All patients had graft detachment, which made air injection necessary. In all cases, visual acuity significantly increased (medium visual acuity [logarithm of the minimum angle of resolution]: 0.68 ± 0.31 logarithm of the minimum angle of resolution after 4 weeks and 0.35 ± 0.37 after 6 months; P = .043), refraction was stable, corneal thickness was reduced (average, 514 ± 11 μm), and endothelial cell count was reduced (average, 1398 ± 510 cells/mm(2)) after 6 months, which corresponds with a medium loss 40%. In the questionnaire, visual outcome, estimated time for recovery, and rehabilitation and patient satisfaction were better after Descemet membrane endothelial keratoplasty than penetrating keratoplasty. No postoperative elevation of pressure, development of pupillary block, or graft rejection, and no peripheral anterior synechiae or other abnormalities were observed with optical coherence tomography during the first 6 postoperative months.Descemet membrane endothelial keratoplasty is a suitable technique for the treatment of graft failure after penetrating keratoplasty and helped our patients rapidly achieve good visual acuity, with reduction of postoperative complications, but the visual outcome might be limited.

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, Charite-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.

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.

Hereditary nephrotic syndrome is a heterogeneous disease, characterized by heavy proteinuria and renal failure. Mutations of NPHS1 or NPHS2, the genes encoding for nephrin and podocin, lead to early onset of heavy proteinuria, and rapid progression to end-stage renal disease, suggesting that both proteins are essential for the integrity of the glomerular filter. Podocin is a stomatin protein family member with a predicted hairpin-like structure localizing to the insertion site of the slit diaphragm of podocytes, the visceral glomerular epithelial cells of the kidney. Here we investigate the pathomechanisms of different disease-causing podocin mutations. We show that wild-type podocin is targeted to the plasma membrane, and forms homo-oligomers involving the carboxy and amino terminal cytoplasmic domains. The association of podocin with specialized lipid raft microdomains of the plasma membrane was a prerequisite for recruitment of nephrin into rafts. In contrast, disease-causing mutations of podocin (R138Q and R138X) failed to recruit nephrin into rafts either because these mutants were retained in the endoplasmic reticulum (R138Q), or because they failed to associate with rafts (R138X) despite their presence in the plasma membrane. None of the mutants did augment nephrin signaling, suggesting that lipid raft targeting facilitates nephrin signaling. Our findings demonstrate that the failure of mutant podocin to recruit nephrin into lipid rafts may be essential for the pathogenesis of NPHS2.

Purpose Netrin-4, a secreted protein, is found in the basement membrane of blood vessels and acts as a key regulator of angiogenesis. Here we investigated the role of Netrin-4 in the mouse-model of suture-induced corneal hem- and lymphangiogenesis. Methods Corneal hem- and lymphangiogenesis were induced in Netrin-4-deficient (Ntn4-/-) and wild-type (WT) mice by placing three 11-0 nylon sutures intrastromally. Fourteen days after suturing, the vascularized area was analyzed via corneal flat mount immunohistochemistry. Messenger RNA levels for VEGF-A, VEGF-C, Lyve-1, Netrin-4, Unc5H2, "deleted in colon cancer" receptor, and Neogenin in treated and nontreated mouse corneas, cultured human corneal keratocytes (HCK) and epithelial cells (HCEC+HCET) were analyzed by quantitative PCR. Results In wild-type mice, Netrin-4 mRNA expression in the cornea decreased in growing corneal neovascularization after suturing. Correspondingly, Ntn4-/- mice showed an increased vascularized area compared to that in WT mice. Expression of VEGF-A mRNA was higher in Ntn4-/- versus WT mice. There was no Netrin-4 expression in lymphatic vessels and the area of lymphatic vascularization did not differ between Ntn4-/- and WT mice, nor did expression of VEGF-C and Lyve-1 mRNA. Human corneal epithelial cells showed mainly Netrin-4 mRNA expression, which increased after stimulation, while HCK demonstrated Unc5H2 mRNA expression. Expression of VEGF-A, Netrin-4, Unc5H2, and Neogenin mRNA in HCEC and HCK did not differ significantly between the serum-free condition and VEGF-A or Netrin-4 stimulation. Conclusions Absence of Netrin-4 increased corneal hemangiogenesis but not lymphangiogenesis in the mouse-model of suture-induced neovascularization. Netrin-4 acted as an antiangiogenic factor in the cornea, with which the healthy cornea is enriched via its expression by corneal epithelial cells.

Descemet membrane endothelial keratoplasty (DMEK) is a standard procedure in patients with endothelial corneal disorders. We investigated the difficulty of unfolding and attaching the graft lamella and its correlation to characteristics of the graft lamella donor, preoperative patient characteristics, and the postoperative outcome. After preparation of the graft lamella, we prospectively graded the unfolding of the graft lamella in 169 consecutive DMEK procedures between September 2012 and August 2013 at the Charite-Universitatsmedizin Berlin with four different grades. Various donor characteristics and preoperative patient characteristics were analyzed and correlated to the grading. Additionally, visual acuity, corneal thickness and endothelial cell density were measured and correlated. Donor characteristics (age [range, 49 – 79 years], gender, endothelial cell density, total storage time, storage de-swelling time, postmortem time) did not correlate to the grading. Preoperative visual acuity significantly influenced the grade of unfolding and attaching of the graft lamella (p = 0.023), while all other preoperative parameters (age, gender, indication for DMEK, preoperative endothelial cell density and preoperative central corneal thickness) showed no correlation. Visual acuity improved significantly after surgery (p

Intraocular pressure (IOP) elevation and post-keratoplasty glaucoma occur commonly after penetrating keratoplasty (PK), but also after Descemet stripping endothelial keratoplasty (DSEK). In this study, we evaluated the risk after Descemet membrane endothelial keratoplasty (DMEK) to develop IOP elevation and post-DMEK glaucoma. The 12-month incidence of IOP elevation and post-DMEK glaucoma was analyzed retrospectively in the first 117 consecutive eyes that underwent DMEK between September 2011 and December 2012 at the Universitatsmedizin–Charite, Berlin. IOP elevation was defined as IOP ≥ 22 mmHg, or ≥10 mmHg from preoperative baseline. The assessment included the pre-operative history of corneal disease and glaucoma. Furthermore, the response to anti-glaucoma treatment, the graft failure, the IOP, the visual acuity, and the endothelial cell count were evaluated. The 12-month incidence of IOP elevation was 12.10 % [95 % confidence interval (CI): 0.94 %, 18.37 %], post-DMEK glaucoma 2.7 % (95 % CI: −0.44 %, 5.84 %). The most frequent cause remained steroid-induced IOP elevation, with an 12-month incidence of 8.0 % (95 % CI: 7.95 %, 8.05 %). In all cases, IOP elevation was treated effectively by tapering down steroid medication and initiating or increasing anti-glaucoma medication. The incidence of postoperative postoperative pupillary block IOP elevation was 15.40 % (95 % CI: 8.93 %, 21.87 %). The number of eyes with iridocorneal contacts after surgery was low (4.2 %). Only the preoperative increased IOP is a significant risk factor for IOP elevation (p = 0.005). Visual acuity improved significantly after surgery (p

Background: Peripheral anterior synechiae (PAS) is a common problem after penetrating keratoplasty (PK) and leads to intraocular pressure (IOP) elevation. This study examines the risk factors for IOP elevation and post-keratoplasty glaucoma. Methods: A retrospective analysis was performed of 47 eyes following PK and of 65 eyes following Descemet's stripping endothelial keratoplasty (DSEK) between 2009 and 2011. The assessment included preoperative history of corneal disease and glaucoma, response to treatment, IOP, and visual acuity. Irido-trabecular contacts (ITC), the angle opening distance (AOD 500) and the anterior chamber angle (ACA 500) were calculated. Results: The incidences of IOP elevation and post-keratoplasty glaucoma were 27-36% and 10-29%, respectively. The incidence did not differ significantly between both procedures. Pre-existing glaucoma increased the risk for developing IOP elevation and post-DSEK glaucoma. Eyes with bullous keratopathy (BK) developed significantly more IOP elevation (p = 0.01, d.f. = 1, χ2 = 6.11) and post-keratoplasty glaucoma (p = 0.01, d.f. = 1, χ2 = 6.22) than eyes with Fuchs' endothelial dystrophy. Eyes with ITC developed post-keratoplasty glaucoma significantly more often than eyes without ITC (p = 0.01, d.f. = 1, χ2 = 6.63). Conclusion: IOP elevation and post-keratoplasty glaucoma showed a high incidence. Risk factors like pre-existing glaucoma, BK and PAS elevated the rate of IOP elevation and post-keratoplasty glaucoma for both procedures. © 2014 S. Karger AG, Basel

Since it has been observed that melanocytic lesions can alter their appearance during pregnancy, we analyzed whether hormone receptors are expressed in conjunctival nevi as well as conjunctival melanoma. We further analyzed whether the number of estrogen (ER) or progesterone receptors (PR) might be associated with the disease course in conjunctival melanoma. Twenty-seven paraffin-embedded samples of conjunctival nevi and 27 conjunctival melanoma specimens were examined using immunohistological analysis with antibodies against PR and ER. The percentage of stained cells were analyzed, taking into account patient gender and age. Out of the melanoma group, all patients with complete data for tumor thickness, tumor localization, age at diagnosis, gender, and follow-up including recurrence, metastasis and tumor-related death were included in the second part of the study (n = 15), where hormone receptor rates were associated with tumor outcome, regarding recurrences, metastasis or death. Written consent was received from all included patients. Both nevi and melanomas showed high rates of PR- and ER-positive cells. In Nevi, 64 ± 25 % of cells stained positive for PR and 35 ± 34 % for ER. In melanoma specimens, 68 ± 30 % showed PR and 44 ± 34 % ER expression. Differences between men and women in expression rates were not statistically significant. Out of 15 melanoma patients (nine female, six male), 53 % (five women and three men) experienced 1—4 recurrences, and four patients developed metastases. The median estimated survival time was 12.2 years. A multivariate survival model taking into account known risk factors for prognosis in conjunctival melanoma confirmed tumor location to be an important predictive factor for outcome (p = 0.05). The rate of PR or ER did not show a statistically significant correlation with the disease course in our cohort. We observed that conjunctival melanocytic lesions express hormone receptors, which could explain why these tumors can alter their appearance under hormonal changes. Regarding the prognosis of conjunctival melanoma, no statistically significant correlation between hormone receptor expression and event-free survival was found in this analysis.

To compare superior vs temporal approach in patients who underwent Descemet membrane endothelial keratoplasty (DMEK).Monocentric, prospective nonmasked study.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.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.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.

A 39-year-old obese woman presented with bilateral blurred vision worsening over 2 days. She also complained of lower back pain for the previous 3 weeks. Her ocular history revealed no abnormalities. Her medical history was significant for HELLP (Haemolysis, Elevated Liver enzyme levels, Low Platelet count) syndrome 12 years ago during her first pregnancy. On examination, best-corrected visual acuity (BCVA) was 20/100 in the right and 20/400 in the left eye. Intraocular pressure, motility and anterior segments of both eyes were normal. Ophthalmoscopy revealed bilateral central serous retinal detachment and several cotton wool spots (figure 1). On general examination, blood pressure (BP) was 230/150 mmHg. Laboratory tests showed leucocytosis (19 700/µl), anaemia (3.77 Mio RBC/µl), thrombocytopenia (57 000/µl), elevated liver enzymes (GOT 58 U/I, GPT 52 U/I, alkaline phosphatase 170 U/I) and impaired renal function (creatinine 1.24 mg/dl). Figure 1 Fundus photography taken on the day of admission, composite image; (A) right eye, (B) left eye; both eyes showed a pronounced central serous retinal detachment on the day of admission. 1. How will you approach a patient presenting with secondary retinal detachment in both eyes of acute origin. What further investigations will you do? 2. How do you manage such a case? 3. Describe the spectral domain optical coherence tomography (OCT) findings (figure 2). Figure 2 Spectral domain optical coherence tomography (OCT), pictures on the left show infrared photography with selected scan, on the right corresponding scan. (A) Right eye: —top, OCT at first presentation; …

To describe new affected individuals of Franceschetti's original pedigree of hereditary recurrent erosion and to classify a unique entity called Franceschetti corneal dystrophy.Observational case series.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.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.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.