Clinical, Anatomical, and Densitometric Changes following Dresden vs. Accelerated Corneal Cross-Linking in Progressive Keratoconus.

BACKGROUND: To compare clinical, anatomical, and densitometric changes following Dresden (DCXL) vs. accelerated (ACXL) corneal UVA cross-linking (CXL; Avedro KXL, Geuder, Heidelberg, Germany) in progressive keratoconus (KC). METHODS AND MATERIAL: In this retrospective study, we analyzed 20 patients following DCXL (3 mW/cm², 30 min, 5.4 J/cm²) and 44 patients following ACXL (9 mW/cm², 10 min, 5.4 J/cm²) between January 2016 and February 2020. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), steepest keratometry (Kmax), keratoconus index (KI), thinnest pachymetry (Pthin), and corneal densitometry (CD) were measured before and 3, 6, 12, and 24 months after CXL. RESULTS: During the follow-up period, no changes in UCVA, BSCVA, Kmax, KI, or Pthin occurred. CCT significantly decreased 3 months after DCXL (p = 0.032) and ACXL (p = 0.006). At the 12- and 24-month follow-up, CCT remained decreased in the DCXL (p = 0.035, 0.036, respectively) but not in the ACXL group. At the 12-month follow-up, the reduction in CCT was significantly greater in DCXL compared to ACXL (p = 0.012). At the 3-, 6-, 12-, and 24-month follow-ups, we found a significant increase in the anterior stroma CD following DCXL (p = 0.019, 0.026, 0.049, 0.047, respectively) but not ACXL. The CD changes were localized in the central concentric zones (0.0 to 6.0 mm). No intra- or postoperative complications occurred. CONCLUSION: ACXL and DCXL effectively halted KC progression. ACXL proved to be a safe time-saving alternative to conventional DCXL. DCXL led to a reduction in CCT and an increment in the CD of the central anterior stroma during 24 months of follow-up.

Short-Term Clinical Results After ILM Removal and Inverted ILM Flap for Macular Hole Repair - A Single-Center Retrospective Experience.

Purpose: To compare results after ILM peeling and ILM inverted flap technique utilized the repair of full thickness macular holes, irrespective of their size. Patients and Methods: Pre- and postoperative data of 109 patients who suffered from a full thickness macular hole were retrospectively analyzed. Forty-eight patients were treated with an inverted ILM flap technique, 61 patients were treated with ILM peeling. All patients received a gas tamponade. The primary endpoint was macular hole closure as demonstrated by OCT scanning. Secondary endpoints were best corrected visual acuity and clinical complication rates. Results: For small and medium-sized macular holes the closure rates in the ILM flap technique group were 100% and 94%, respectively. For ILM peeling, the closure rate was identical (95%). For large macular holes, the closure rate was 100% in the flap versus 50% in the ILM peeling group, but visual acuity improved in both groups (ILM flap p=0.001, ILM peeling p=0.002). In both treatment groups, larger holes were associated with a reduced final visual outcome. For medium-sized macular holes, visual acuity significantly improved only in the ILM peeling group. Both techniques were associated with minimal and comparable side effects. Conclusion: In our limited series, the inverted ILM flap technique for repair of macular holes demonstrated a high closure rate. For large MHs, we saw a trend towards a better closure rate in the flap technique compared to ILM peel only. However, final visual acuity showed no significant difference between the groups. Clinical results and complications appeared to be comparable in both groups.

TREATMENT OF PERSISTENT MACULAR HOLES WITH HEAVY SILICONE OIL.

BACKGROUND/PURPOSE: To determine anatomical success and best-corrected visual acuity after secondary surgery with heavy silicone oil tamponade in patients with persistent full-thickness macular holes. METHODS: In this retrospective study, 63 eyes with persistent full-thickness macular holes after primary pars plana vitrectomy and internal limiting membrane peeling underwent secondary surgery with heavy silicone oil tamponade. Macular spectral domain optical coherence tomography and best-corrected visual acuity measurements were performed during the follow-up. RESULTS: Fifty of 63 eyes (79.4%) achieved anatomical success. In eyes achieving anatomical success, best-corrected visual acuity before primary vitreoretinal surgery was significantly better (0.77 [∼20/125 Snellen] ± 0.24 [1.3-0.3] logarithm of the minimum angle of resolution) compared with eyes not achieving anatomical success (0.88 [∼20/160 Snellen] ± 0.17 [1.1-0.6] logarithm of the minimum angle of resolution, P = 0.044). Minimum linear diameter of full-thickness macular holes was significantly smaller in eyes achieving anatomical success, both before primary (403.4 ± 128.7 [199.0-707.0] µ m vs. 568.1 ± 209.1 [307.0-953.0] µ m, P = 0.009) and secondary surgery (464.1 ± 215.0 [178.0-1,521.0] µ m vs. 663.3 ± 228.5 [451.0-1,301.0] µ m, P = 0.010). Patients remaining phakic during all three surgeries did not benefit from best-corrected visual acuity improvement, although anatomical success was achieved. CONCLUSION: Heavy silicone oil tamponade in secondary surgery for persistent full-thickness macular holes is a safe and efficient surgical method. Best-corrected visual acuity and minimum linear diameter before surgery may be indicators for anatomical success.

[Endophthalmitis after perforation of the conjunctiva by a glaucoma gel-stent implant]. / Endophthalmitis nach Bindehautperforation eines Glaukom-Gelstentimplantates.

Intraocular infections associated with Abiotrophia defectiva are rare. This article reports the case of a 57-year-old woman with endophthalmitis associated with Abiotrophia defectiva 3 months after uncomplicated cataract surgery combined with the implantation of a glaucoma gel-stent in the right eye. The patient had complained of redness of the right upper nasal conjunctiva and pain for 2 weeks prior to the endophthalmitis. A topical steroid eyedrop treatment without antibiotic additives had temporarily improved the situation. The patient presented with hypopyon, acute deterioration of vision and severe periocular pain of the right eye since the early morning. The gel-stent had spontaneously perforated the conjunctiva. The patient was immediately started on local and systemic antibiotics and underwent pars plana vitrectomy with intravitreal antibiotic application 6 h after presentation. Unlike other ocular infections with Abiotrophia defectiva, this case had a relatively benign course most likely due to the prompt intervention. In clinical routine, patients, who present with acute deterioration of vision and pain after glaucoma surgery, should be examined urgently considering a possible spontaneous conjunctival perforation and late onset endophthalmitis. Additionally, conjunctivitis of unclear origin following ocular surgery should always be treated with antibiotics, particularly when steroids are administered and monitored closely.

Antiangiogenic and Neurogenic Activities of Sleeping Beauty-Mediated PEDF-Transfected RPE Cells In Vitro and In Vivo.

Pigment epithelium-derived factor (PEDF) is a potent multifunctional protein that inhibits angiogenesis and has neurogenic and neuroprotective properties. Since the wet form of age-related macular degeneration is characterized by choroidal neovascularization (CNV), PEDF would be an ideal candidate to inhibit CNV and support retinal pigment epithelial (RPE) cells. However, its short half-life has precluded its clinical use. To deliver PEDF to the subretinal space, we transfected RPE cells with the PEDF gene using the Sleeping Beauty transposon system. Transfected cells expressed and secreted biologically active recombinant PEDF (rPEDF). In cultures of human umbilical vein endothelial cells, rPEDF reduced VEGF-induced cumulative sprouting by ≥47%, decreased migration by 77%, and increased rate of apoptosis at least 3.4 times. rPEDF induced neurite outgrowth in neuroblastoma cells and protected ganglion and photoreceptor cells in organotypic retinal cultures. In a rat model of CNV, subretinal transplantation of PEDF-transfected cells led to a reduction of the CNV area by 48% 14 days after transplantation and decreased clinical significant lesions by 55% and 40% after 7 and 14 days, respectively. We showed that transplantation of pigment epithelial cells overexpressing PEDF can restore a permissive subretinal environment for RPE and photoreceptor maintenance, while inhibiting choroidal blood vessel growth.

Importance of junctional adhesion molecule-C for neointimal hyperplasia and monocyte recruitment in atherosclerosis-prone mice-brief report.

OBJECTIVE: Although junctional adhesion molecule (JAM)-C has been implicated in the control of inflammatory leukocyte recruitment, its role in neointima formation after arterial injury has not been elucidated. METHODS AND RESULTS: In apolipoprotein E-deficient (Apoe(-/-)) mice fed an atherogenic diet, antibody blockade of JAM-C significantly reduced neointimal hyperplasia after wire injury of carotid arteries without altering medial area and decreased neointimal macrophage but not smooth muscle cell (SMC) content. An increased expression of JAM-C was detected in colocalization with luminal SMCs 1 day after injury and neointimal SMCs after 3 weeks. Blocking JAM-C inhibited monocytic cell arrest and leukocyte adhesion to carotid arteries perfused ex vivo and in vivo. Furthermore, monocyte adhesion to activated coronary artery SMCs under flow conditions in vitro was diminished by blocking JAM-C. CONCLUSIONS: Our data provide the first evidence for a crucial role of JAM-C in accelerated lesion formation and leukocyte recruitment in atherosclerosis-prone mice.

C1-esterase inhibitor protects against neointima formation after arterial injury in atherosclerosis-prone mice.

BACKGROUND: Although activation of the complement system has been implicated in the progression of human atherosclerosis, its function during arterial remodeling after injury has not been investigated. Here, we examined the contribution of the complement cascade to neointima formation in apolipoprotein E-deficient mice using a C1-esterase inhibitor (C1-inhibitor). METHODS AND RESULTS: Apolipoprotein E-deficient mice fed an atherogenic diet were subjected to wire-induced endothelial denudation of the carotid artery and treated with C1-inhibitor (Berinert; 15 IU i.v.) or vehicle perioperatively and subsequently every 2 days. The effectiveness of C1-inhibitor treatment was confirmed by measurement of plasma C1-inhibitor activity. A significant reduction in serum triglyceride levels was observed in C1-inhibitor-treated mice, whereas cholesterol levels did not differ. After 3 weeks, neointimal area was significantly reduced in C1-inhibitor-treated mice versus controls, whereas medial area was unaltered. This was associated with a significant decrease in neointimal and medial macrophage and CD3+ T-cell content. Expression of C3 mRNA was significantly reduced in plaques of C1-inhibitor-treated mice 10 days after injury, as assessed by reverse-transcription polymerase chain reaction. The peak in serum C3 levels after injury was markedly downregulated by C1-inhibitor, as evidenced by ELISA. Immunohistochemistry revealed strong expression of C3 and C3c, which colocalized to plaque macrophages and was reduced in C1-inhibitor-treated mice. C1-inhibitor impaired monocyte arrest on activated endothelium and platelets under flow conditions in vitro and leukocyte recruitment to carotid arteries 1 day after injury in vivo. CONCLUSIONS: C1-inhibitor limits neointimal plaque formation and inflammation. This may involve blockade of complement activation, inhibition of leukocyte recruitment, and reduced triglyceride levels, thus providing a multimodal approach to treat arterial disease.

Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis.

The CXC ligand (CXCL)12/CXC receptor (CXCR)4 chemokine-receptor axis controls hematopoiesis, organ development, and angiogenesis, but its role in the inflammatory pathogenesis of atherosclerosis is unknown. Here we show that interference with Cxcl12/Cxcr4 by a small-molecule antagonist, genetic Cxcr4 deficiency, or lentiviral transduction with Cxcr4 degrakine in bone marrow chimeras aggravated diet-induced atherosclerosis in apolipoprotein E-deficient (Apoe-/-) or LDL receptor-deficient (Ldlr-/-) mice. Chronic blockade of Cxcr4 caused leukocytosis and an expansion of neutrophils and increased neutrophil content in plaques, associated with apoptosis and a proinflammatory phenotype. Whereas circulating neutrophils were recruited to atherosclerotic lesions, depletion of neutrophils reduced plaque formation and prevented its exacerbation after blocking Cxcr4. Disrupting Cxcl12/Cxcr4 thus promotes lesion formation through deranged neutrophil homeostasis, indicating that Cxcl12/Cxcr4 controls the important contribution of neutrophils to atherogenesis in mice.