XEN®-45 implantation for refractory uveitic glaucoma.

PURPOSE: To evaluate the efficacy of XEN®-45 gel stent ab interno implantation for medically uncontrolled uveitic glaucoma. METHODS: Retrospective analysis of 25 eyes receiving XEN® gel stent for medically uncontrolled uveitic glaucoma from February 2019 to February 2023 with recording of intraocular pressure (IOP) values, ocular hypotensive medication, requirement for revision or secondary surgery and complications. Prerequisites for XEN® implantation were a clear cornea, an open iridocorneal angle and an unscarred, mobile conjunctiva at the implantation site. Minimum follow-up required for inclusion was 3 months. The primary outcome measure was IOP compared to baseline. Complete and qualified success were defined as final IOP of ≤ 18 mmHg without or with topical antiglaucomatous treatment, respectively. Failure was defined as IOP > 18 mmHg on two consecutive visits, IOP reduction < 20%, persisting complications from hypotony and open conjunctival bleb revision. Further glaucoma surgical intervention was defined as complete failure. RESULTS: Mean preoperative IOP was 35.3 ± 10.9 mmHg on 2.9 ± 0.9 topical antiglaucomatous agents. 19 of 25 patients (76%) received additional oral acetazolamide. 19 eyes were pseudophakic, 5 eyes phakic and 1 aphakic. Early postoperatively, mean IOP reduced to 7.7 ± 3.0 mmHg (75.8% reduction). At final follow-up (mean 17.7 months) mean IOP was 12.0 ± 3.8 mmHg (62.5% reduction) on 0.2 ± 0.6 medications. Six eyes (24%) required bleb revision at mean 28 weeks and therefore were categorized as failure. One eye failed despite bleb revision and restart of topical ocular hypotensive medication. Three other eyes (12%) had IOP spikes with uveitis flare-ups. Transient hypotony complications occurred in 32%. At final follow-up, 18 eyes (72%) achieved complete success and one eye (4%) qualified success. CONCLUSION: The XEN® gel stent effectively reduced IOP in uncontrolled uveitic glaucoma, with 72% complete success. Bleb revision was required in 24%. IOP spikes occurred in 12% despite functioning blebs. Further follow-up is needed to determine long-term outcomes.

[Primary Open Angle Glaucoma]. / Das primäre Offenwinkelglaukom.

Primary open angle glaucoma is the most frequent type among the glaucomas. It is characterized by a progressive loss of retinal ganglion cells and a corresponding visual field loss. Risk factors include older age, ethnicity, family history of glaucoma and, most important, an elevated intraocular pressure (IOP). The IOP is the only modifiable risk factor for glaucoma progression. Therapeutic approaches aim to lowering the IOP and incorporate topical pressure lowering medication, laser treatment, and different surgical approaches. Surgery aims to reducing the outflow resistance of the aqueous humor. This may be achieved by surgically opening the trabecular meshwork or Schlemm's canal. Penetrating glaucoma surgery comprises classic trabeculectomy and other draining devices.

Descemet Membrane Endothelial Keratoplasty in Eyes with an Artificial Iris.

The purpose of this study is to report the outcome of Descemet membrane endothelial keratoplasty (DMEK) in three eyes with a complex anterior segment and an artificial iris. A retrospective chart review of three cases was performed and clinically meaningful patient characteristics, clinical events, and therapeutic interventions were outlined. A literature search was performed and the clinical course of the three cases was discussed in the context of the published literature. DMEK in the presence of an artificial iris did not match the clinical results of DMEK in uncomplicated eyes. All three eyes experienced major complications, such as failure to achieve graft adherence, early graft failure, or an immune reaction. The indication for DMEK in complex anterior segments with an artificial iris should be made with the awareness of multiple possible complications and the potentially poor prognosis of the procedure.

Clinical Course of Different Types of Immune Reactions following Keratoplasty.

BACKGROUND: Immune-mediated corneal graft rejection (IR) is a leading cause of corneal graft failure. The endothelium, stroma, epithelium, or a combination can be affected. Little is known about the long-term outcomes of different types of IR. METHODS: We reviewed the medical records of all keratoplasties that had been performed at our eye centre between 2003 and 2016 (n = 3934) for any kind of IR that occurred between the surgery and 2019. All patients with a definite diagnosis of IR and sufficient clinical data were included in the analysis. IRs were grouped according to the affected part of the graft (endothelial, stromal, epithelial, and mixed). We analysed the dynamics of recovery and the clinical outcomes. RESULTS: We identified a total of 319 patients with IR. Twenty-seven of those were lost to follow-up and were excluded from further analysis. Of the IRs, 89% affected the endothelium. Endothelial IR resulted more frequently in a considerable loss of endothelial cell density than other forms of IR. Stromal IR showed a lower relapse rate and a better visual recovery than other types of IR and resulted less often in a failure of the graft. CONCLUSIONS: We herein report comprehensive data about the prognosis regarding functional recovery after different types of IR following keratoplasty. Our data underline that timely recognition and correct classification of IR are important because they determine the clinical course and prognosis.

Clinical Results of the MINIject Implant for Suprachoroidal Drainage.

Objective: This retrospective study evaluated the safety and efficacy of the new minimally invasive MINIject implant placed in the suprachoroidal space. The aim was to assess its impact on intraocular pressure (IOP) reduction and complication rate. Methods: 18 eyes from 18 patients with insufficiently controlled glaucoma received the implant using topical medications. Outcomes were changes in IOP, change in IOP medication, need for other glaucoma surgery, and rate of adverse events. Results: IOP reduced by 15% (p < 0.05) following MINIject implantation. IOP medication decreased from 3 to 1 agent (p < 0.05). Four patients (22%) required other glaucoma surgery while we did not observe any clinically relevant adverse event. Conclusions: This retrospective study indicates that MINIject implants may be a safe and effective means of reducing IOP together with a reduction in IOP medications in most patients. Larger prospective studies with longer follow-ups are necessary to confirm our results, though.

Reassessing Trabeculectomy: A Long-Term Study with Stringent Success Criteria.

Background: The aim was to evaluate the long-term outcome and efficacy of primary trabeculectomy with adjunctive mitomycin c (MMC) for treating glaucoma. Methods: We examined the medical records of 286 eyes that underwent trabeculectomy between 2008 and 2009 at the University Eye Hospital in Freiburg, Germany. Preoperative and follow-up data were collected, including intraocular pressure (IOP) measurements, surgical glaucoma interventions, and prescribed glaucoma medication. The first success criterion was defined as IOP ≤ 15 mmHg with no use of pressure-lowering medication by the patient, the second criterion was defined as the absence of surgical revision, and the third criterion as no further IOP-lowering surgery excluding early revisions following trabeculectomy. Statistical analyses comprised Cox regression and Kaplan-Meier survival estimations. Results: The mean follow-up duration was 1841 days (5 years). The mean preoperative IOP was 26.1 mmHg. Evaluating the success criteria at the time of average follow-up yielded a success rate of only 25% for the first criterion but 80% for both the second and third success criteria. Conclusions: The findings suggest that trabeculectomy with adjunctive MMC can be an effective procedure for permanently lowering IOP. However, surgical revisions and/or further glaucoma surgeries might still be needed. The long-term success rate is lower in comparison to previous research, which may be explained by the stricter success criteria in our study.

Management of Belantamab Mafodotin-Associated Keratopathy With Rigid Gas-Permeable Corneal Contact Lenses.

ABSTRACT: Belantamab mafodotin is a relatively new drug used in the treatment of relapsed or refractory multiple myeloma. Clinical studies have shown promising responses, but ocular toxicity remains a major challenge with dose reduction or therapy discontinuation being the only available treatment option. We report a clinical case of a patient with severe keratopathy under therapy with belantamab. The use of rigid gas-permeable corneal contact lenses led to a major visual improvement and enabled therapy continuation at full dose over several months. Although this strategy may not be suitable for all patients, it provides an additional option for the treatment of ocular toxicity of this promising agent.

Comparison between Intraocular Pressure Profiles over 24 and 48 h in the Management of Glaucoma.

(1) Background: Due to significant variation, sporadic IOP measurements often fail to correctly assess the IOP situation in glaucoma patients. Thus, diurnal-nocturnal IOP profiles can be used as a diagnostic tool. The purpose of this study is to determine the additional diagnostic value of prolonged IOP profiles. (2) Methods: All diagnostic 48 h IOP profiles from a large university hospital, between 2017 and 2019, were reviewed. Elevated IOP > 21 mmHg, IOP variation > 6 mmHg and nocturnal IOP peaks were defined as IOP events of interest and counted. The analysis was repeated for the first 24 h of every IOP profile only. The Chi2 test was used for statistical analysis. (3) Results: 661 IOP profiles were included. Specifically, 59% of the 48 h IOP profiles revealed IOP values above 21 mmHg, and 87% showed IOP fluctuation greater than 6 mmHg. Nocturnal peaks in the supine position could be observed in 51% of the patients. In the profiles censored for the first 24 h, the fractions were 50%, 71% and 48%, (p < 0.01, p < 0.01 and p = 0.12) respectively. (4) Conclusions: the 48 h IOP profiles identified more patients with IOP events of interest than the 24 h IOP profiles. The additional diagnostic value must be weighed against the higher costs.

XEN®-63 Compared to XEN®-45 Gel Stents to Reduce Intraocular Pressure in Glaucoma.

The XEN® gel stent reduces intraocular pressure (IOP) in glaucoma. XEN®-45 is widely used; the newer XEN®-63 has a larger lumen targeting potentially lower IOP outcomes. We retrospectively compared the first 15 XEN®-63 cases to 15 matched XEN®-45 controls. With a preoperative IOP of 18.1 ± 3.9 mmHg (mean ± SD) and a final IOP of 9.1 ± 2.0 mmHg, XEN®-63 implantation resulted in an IOP reduction of 44.6 ± 16.5%. Similarly, with a preoperative IOP of 18.3 ± 4.5 mmHg and a final IOP of 10.3 ± 2.1 mmHg, XEN®-45 implantation resulted in an IOP reduction of 40.1 ± 17.2%. The median follow-up period was 204 days (range 78-338 days) for the XEN®-63 group and 386 days (range 99-1688 days) for the XEN®-45 group. In total, 5/15 eyes of each group underwent open conjunctival bleb revision within the period of observation. Three eyes of the XEN®-63 group had secondary glaucoma surgery. One eye in the XEN®-63 group and three eyes in the XEN®-45 group required a restart of antiglaucomatous medication. In conclusion, both stents effectively lower IOP and medication. XEN®-63 achieved a slightly lower IOP over a short follow-up. Complication and revision rates were similar.

The IL-3, IL-5, and GM-CSF common receptor beta chain mediates oncogenic activity of FLT3-ITD-positive AML.

FLT3-ITD is the most predominant mutation in AML being expressed in about one-third of AML patients and is associated with a poor prognosis. Efforts to better understand FLT3-ITD downstream signaling to possibly improve therapy response are needed. We have previously described FLT3-ITD-dependent phosphorylation of CSF2RB, the common receptor beta chain of IL-3, IL-5, and GM-CSF, and therefore examined its significance for FLT3-ITD-dependent oncogenic signaling and transformation. We discovered that FLT3-ITD directly binds to CSF2RB in AML cell lines and blasts isolated from AML patients. A knockdown of CSF2RB in FLT3-ITD positive AML cell lines as well as in a xenograft model decreased STAT5 phosphorylation, attenuated cell proliferation, and sensitized to FLT3 inhibition. Bone marrow from CSF2RB-deficient mice transfected with FLT3-ITD displayed decreased colony formation capacity and delayed disease onset together with increased survival upon transplantation into lethally irradiated mice. FLT3-ITD-dependent CSF2RB phosphorylation required phosphorylation of the FLT3 juxtamembrane domain at tyrosines 589 or 591, whereas the ITD insertion site and sequence were of no relevance. Our results demonstrate that CSF2RB participates in FLT3-ITD-dependent oncogenic signaling and transformation in vitro and in vivo. Thus, CSF2RB constitutes a rational treatment target in FLT3-ITD-positive AML.

[Treatment of Descemet's membrane detachment after cataract surgery : Successful visual recovery by repeated injection of air into the anterior chamber]. / Therapie der Descemetolyse nach Kataraktoperation : Erfolgreiche Visusrehabilitation durch wiederholte intrakamerale Lufteingabe.

Descemet's membrane detachment (DMD) is a rare complication following cataract surgery. The characteristic clinical sign is a severe persisting corneal edema early after surgery without spontaneous improvement. Descemet's membrane can sometimes be seen partially floating in the anterior chamber. Optical coherence tomography of the anterior segment can help to determine the extent of DMD. The decision to choose a conservative watch and wait approach or a surgical intervention depends on the height, length and extent of the detachment as well as the localization in relation to the optical axis. Detachments of greater extent require surgical treatment and the first line treatment should be descemetopexy by injection of air into the anterior chamber of the eye. Subsequently, regular controls are necessary as DMD may require repeated air injections until reattachment of Descemet's membrane is achieved and the cornea becomes clear again.

CCL5 mediates target-kinase independent resistance to FLT3 inhibitors in FLT3-ITD-positive AML.

FLT3-ITD tyrosine kinase inhibitors (TKI) show limited clinical activity in acute myeloid leukemia (AML) due to emerging resistance. TKI resistance is mediated by secondary FLT3-ITD mutations only in a minority of cases. We hypothesize that the cytokine CCL5 protects AML cells from TKI-mediated cell death and contributes to treatment resistance. We generated PKC412- and sorafenib-resistant MOLM-13 cell lines as an in vitro model to study TKI resistance in AML. Increased CCL5 levels were detected in supernatants from PKC412-resistant cell lines compared to TKI-sensitive cells. Moreover, CCL5 treatment of TKI-sensitive cells induced resistance to PKC412. In resistant cell lines with high CCL5 release, we observed a significant downregulation of the CCL5-receptor CCR5 and CXCR4. In these cell lines, TKI resistance could be partly overcome by addition of the CXCR4-receptor antagonist plerixafor. Microarray and intracellular flow cytometry analyses revealed increased p-Akt or p-Stat5 levels in PKC412-resistant cell lines releasing high amounts of CCL5. Treatment with the CXCR4 antagonist plerixafor, αCCL5, or CCR5-targeting siRNA led to a decrease of p-Akt-positive cells. Transient transfection of sensitive MOLM-13 cells with a CCL5-encoding vector mediated resistance against PKC412 and led to an increase in p-Akt-positive and p-Stat5-positive cells. Isolated AML blasts from patients treated with PKC412 revealed that CCL5 transcript levels increase significantly at relapse. Taken together, our findings indicate that CCL5 mediates resistance to FLT3-TKIs in FLT3-ITD-mutated AML and could possibly serve as a biomarker to predict drug resistance.