Pseudophakic corneal donor tissue in Descemet membrane endothelial keratoplasty (DMEK): implications for cornea banks and surgeons

Objective: Increasingly, cornea banks are recovering donor tissue from pseudophakic donors. Little is known about their suitability for Descemet membrane endothelial keratoplasty (DMEK) surgery in terms of endothelial cell density (ECD) and preparation failure. Methods and Analysis: We explored ECD during donor tissue preparation in 2076 grafts. Preparation failure was analysed in 1028 grafts used in DMEK surgery at our clinic. To monitor ECD and functional results, we matched 86 DMEK patients who received pseudophakic donor grafts with similar recipients of phakic donor grafts and followed them up for 36 months. Results: At recovery, mean ECD in pseudophakic donor grafts was 2193 cells/mm2 (SD 28.7) and 2364 cells/mm2 (SD 15.7) in phakic donor grafts (p<0.001). After cultivation, the difference increased as pseudophakic donor grafts lost 14% of ECD while phakic lost only 6% (p<0.001). At transplantation, mean ECD in pseudophakic donor grafts was 2272 cells/mm2 (SD 250) and 2370 cells/mm2 (SD 204) in phakic donor grafts (p<0.001). After transplantation, the difference in ECD increased as pseudophakic donor grafts lost 27.7% of ECD while phakic donor grafts lost only 13.3% (p<0.001). The risk of preparation failure in pseudophakic donor grafts was higher than in phakic donor grafts (OR 4.75, 95% CI 1.78 to 12.67, p=0.02). Visual acuity increased in both groups similarly. Conclusions: Pseudophakic donor grafts have a lower ECD, are more prone to endothelial cell loss during recovery and surgery and are associated with a higher risk of preparation failure. Cornea banks and surgeons should consider this in the planning of graft preparation and transplantation

Macular, papillary and peripapillary perfusion densities measured with optical coherence tomography angiography in primary open angle glaucoma and pseudoexfoliation glaucoma

Purpose: To compare the blood flow situation in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) using optical coherence tomography angiography (OCTA). Methods: In this prospective study a total of 26 POAG and 23 PXG eyes were included. All patients underwent a complete ophthalmological examination including standard automated perimetry, stereoscopic photographs of the optic disc, peripapillary retinal nerve fibre layer analysis and examination of vascular parameters of the optic nerve head (ONH), the peripapillary region and macula using OCTA. In addition to the vascular parameters recorded by the device, the vascular images were graphically evaluated using Image J. All recorded vascular parameters were compared between both groups and correlated to structural and functional parameters. Results: The mean superficial perifoveal plexus perfusion density (PD) was significantly lower in PXG eyes than compared to POAG eyes using OCTA (32.57% +/- 3.57% vs. 34.92% +/- 2.11%, p = 0.007). The mean PD parameters for the superficial peripapillary plexus (40.98% +/- 3.04% vs. 42.09% +/- 2.29%, p = 0.152) as well as the size of the foveal avascular zone (FAZ) (0.23 mm(2) +/- 0.1 mm(2) vs. 0.23 mm(2) +/- 0.09 mm(2)) did not differ between both groups. Additional graphic evaluation using Image J showed no significant difference for superficial perifoveal plexus PD (32.97% +/- 1.11% vs. 33.35% +/- 0.95%, p = 0.194) and peripapillary plexus PD (46.65% +/- 0.83% vs. 46.95% +/- 0.5%, p = 0.127) between the groups. Retinal nerve fibre layer (RNFL) thickness correlated significantly with peripapillary plexus PD for both OCTA data and Image J data (p < 0.001, p = 0.032). Conclusion: The severity of the glaucoma seems to be crucial for peripapillary and macular perfusion densities, and not the form of glaucoma. An additional graphic evaluation is a possible step that could be implemented to improve the comparability of OCTA scans and to optimize the possibility of quantitative perfusion analysis in the case of deviating quality criteria

Exploring the precision of femtosecond laser-assisted descemetorhexis in Descemet membrane endothelial keratoplasty

Objective Descemet membrane endothelial keratoplasty (DMEK) remains a challenging technique. We compare the precision of femtosecond laser-assisted DMEK to manual DMEK. Methods and Analysis A manual descemetorhexis (DR) of 8 mm diameter was compared with a femtosecond laser-assisted DR of the same diameter (femto-DR) in 22 pseudophakic patients requiring DMEK. We used OCT images with a centred xy-diagram to measure the postoperative precision of the DR and the amount of endothelial denuded area. Endothelial cell loss (ECL) and best corrected visual acuity were measured 3 months after surgery. Results In the manual group, the median error of the DR was 7% (range 3%-16%) in the x-diameter and 8% (range 2%-17%) in the y-diameter. In the femto group, the median error in the respective x and y-diameters was 1% (range 0.4%-3%) and 1% (range 0.006%-2.5%), smaller than in the manual group (p=0.001). Endothelial denuded areas were larger in the manual group (11.6 mm(2), range 7.6-18 mm(2)) than in the femto group (2.5 mm(2), range 1.25.9 mm(2)) (p<0.001). The ECL was 21% (range 5%-78%) in the manual DR and 17% (range 6%-38%) in the femto-DR group (p=0.351). The median visual acuity increased from 0.4 logMAR (range 0.6-0.4 logMAR) in both groups to 0.1 logMAR (range 0.4-0 logMAR) in the manual group and to 0.1 logMAR (range 0.3-0 logMAR) in the femto group (p=0.461). Three rebubblings were required in the manual group, whereas the femto group required only one. Conclusion The higher precision of the femto-DR bears the potential to improve DMEK surgery

Influence of Selective Laser Trabeculoplasty (SLT) on the iStent inject® outcomes

Background: To evaluate the influence of Selective Laser Trabeculoplasty (SLT) on iStent inject® outcomes in open-angle glaucoma (OAG). Methods: In this retrospective comparative cohort outcome study, 66 patients who were treated with two iStent inject® devices were included. Patients were divided into two subgroups consisting of patients without SLT treatment prior to surgery and patients who had been treated previously with 360° SLT but without sufficient response. Outcome measures included intraocular pressure (IOP) and number of antiglaucoma medications after 6 weeks with three, six, 12, and 24 month follow-ups. Results: Mean preoperative IOP decreased from 20.4 ± 5.3 mmHg to 14.8 ± 3.0 mmHg for patients without SLT treatment prior to surgery (p = 0.001) and from 19.2 ± 4.5 mmHg to 14.0 ± 1.6 mmHg for patients with insufficient response to 360° SLT treatment (p = 0.027) at 12 months after iStent inject® implantation. No significant difference was found between the two groups (p > 0.05). The number of antiglaucoma medications did not change in both groups (p > 0.05) and showed no significant difference between the two groups (p > 0.05). Conclusion: Prior SLT treatment seems to have no negative influence on the IOP lowering-effect of iStent inject® implantation in patients with OAG. It is therefore an appropriate incremental procedure with no exclusion criterion for an iStent inject® implantation

Effects of TNFα receptor TNF-Rp55- or TNF-Rp75- deficiency on corneal neovascularization and lymphangiogenesis in the mouse

Tumor necrosis factor (TNF)α is an inflammatory cytokine likely to be involved in the process of corneal inflammation and neovascularization. In the present study we evaluate the role of the two receptors, TNF-receptor (TNF-R)p55 and TNF-Rp75, in the mouse model of suture-induced corneal neovascularization and lymphangiogenesis. Corneal neovascularization and lymphangiogenesis were induced by three 11–0 intrastromal corneal sutures in wild-type (WT) C57BL/6J mice and TNF-Rp55-deficient (TNF-Rp55d) and TNF-Rp75-deficient (TNF-Rp75d) mice. The mRNA expression of VEGF-A, VEGF-C, Lyve-1 and TNFα and its receptors was quantified by qPCR. The area covered with blood- or lymphatic vessels, respectively, was analyzed by immunohistochemistry of corneal flatmounts. Expression and localization of TNFα and its receptors was assessed by immunohistochemistry of sagittal sections and Western Blot. Both receptors are expressed in the murine cornea and are not differentially regulated by the genetic alteration. Both TNF-Rp55d and TNF-Rp75d mice showed a decrease in vascularized area compared to wild-type mice 14 days after suture treatment. After 21 days there were no differences detectable between the groups. The number of VEGF-A-expressing macrophages did not differ when comparing WT to TNF-Rp55d and TNF-Rp75d. The mRNA expression of lymphangiogenic markers VEGF-C or LYVE-1 does not increase after suture in all 3 groups and lymphangiogenesis showed a delayed effect only for TNF-Rp75d. TNFα mRNA and protein expression increased after suture treatment but showed no difference between the three groups. In the suture-induced mouse model, TNFα and its ligands TNF-Rp55 and TNF-Rp75 do not play a significant role in the pathogenesis of neovascularisation and lymphangiogenesis

Virus-associated anterior uveitis and secondary glaucoma: Diagnostics, clinical characteristics, and surgical options

In this retrospective, single-center, observational study, we compared the clinical characteristics, analyzed the glaucoma development, and the glaucoma surgery requirement mediators in patients with different virus-associated anterior uveitis (VAU). In total, 270 patients (= eyes) with VAU confirmed by positive Goldmann-Witmer coefficients (GWC) for cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), rubella virus (RV), and multiple virus (MV) were included. Clinical records of these patients were analyzed. Demographic constitution, clinical findings, glaucoma development, and surgeries were recorded. The concentrations of 27 immune mediators were measured in 150 samples of aqueous humor. The GWC analysis demonstrated positive results for CMV in 57 (21%), HSV in 77 (29%), VZV in 45 (17%), RV in 77 (29%), and MV in 14 (5%) patients. CMV and RV AU occurred predominantly in younger and male patients, while VZV and HSV AU appeared mainly with the elderly and females (P<0.0001). The clinical features of all viruses revealed many similarities. In total, 52 patients (19%) showed glaucomatous damage and of these, 27 patients (10%) needed a glaucoma surgery. Minimal-invasive glaucoma surgery (MIGS) showed a reliable IOP reduction in the short-term period. In 10 patients (37%), the first surgical intervention failed and a follow-up surgery was required. We conclude that different virus entities in anterior uveitis present specific risks for the development of glaucoma as well as necessary surgery. MIGS can be suggested as first-line-treatment in individual cases, however, the device needs to be carefully chosen by experienced specialists based on the individual needs of the patient. Filtrating glaucoma surgery can be recommended in VAU as an effective therapy to reduce the IOP over a longer period of time

Visual outcomes and complications following posterior iris-claw aphakic intraocular lens implantation combined with penetrating keratoplasty

Abstract Background To evaluate the indication, visual outcome, and complication rate after implantation of a posterior iris-claw aphakic intraocular lens (IOL) during penetrating keratoplasty. Methods This retrospective study comprised 23 eyes (23 patients) without adequate capsule support undergoing posterior iris-claw aphakic IOL implantation (Verisyse™/ Artisan®) during penetrating keratoplasty between 2005 and 2010. Mean follow-up was 18 months (range from 12 to 37 months). Results The IOLs were inserted during an IOL exchange in 17 eyes and as a secondary procedure in six aphakic eyes. Pseudophakic bullous keratopathy with corneal scar after anterior chamber intraocular lens (ACIOL) was the main indication for penetrating keratoplasty in 16 eyes (69.6 %). The final corrected distance visual acuity (CDVA) in logMAR (mean 1.0 ± 0.46) improved significantly (p &lt; 0.05) compared to the preoperative CDVA (mean 1.8± 0.73). Twenty eyes (86.9 %) had a final visual acuity in logMAR better than the pre-operative CDVA. The mean postoperative IOP 16.3 mmHg±4.0 was not significantly (p &gt; 0.05) higher compared to the preoperative IOP 15.6 mmHg±5.1. Complications included slight temporary pupil ovalization in three eyes (13.0 %) and iris-claw IOL sublocation in three eyes (13.0 %); all IOLs could be easily repositioned. Cystoid macular edema occured in one eye (4.3 %) 8 weeks after primary surgery. All grafts remained clear without any sign of graft rejection. Conclusions Retropupillar iris-claw IOL during penetrating keratoplasty provides good visual outcomes with a favorable complication rate, and can be used for a wide range of indications in eyes without adequate capsule support

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis