Anterior Segment Complications Following Intravitreal Injection.

Intravitreal injections (IVI s) have gained increased popularity in the past decades and are used to treat a multitude of ailments. In 2010, the total number of IVI s surpassed the number of cataract surgeries performed, making it the most common procedure in ophthalmology. As the number of injections increases, so does the number of injected-related complications. While complications in the posterior segment, such as retinal detachment or endophthalmitis, are detrimental to visual function and have therefore been well documented, IVI s can also lead to complications in the anterior segment. These include hyphema, inflammation of the sterile anterior segment (incidence rate of 0.05 to 1.1% depending on the drug), implant migration with corneal decompensation (incidence rate of 0.43%), iatrogenic lens damage (incidence rate of 0.07%), accelerated cataract formation (up to 50% for steroids and 10.9% for anti-VEGF), and an increased complication rate during subsequent cataract surgery (up to 4% per IVI). Most of these complications occur immediately and have a good prognosis if treated correctly. However, the increased risk of complications during subsequent surgery demonstrates that IVI s can also have long-term complications, a topic that needs to be explored further in future research projects.

Peripheral apoptosis and limited clonal deletion during physiologic murine B lymphocyte development.

Self-reactive and polyreactive B cells generated during B cell development are silenced by either apoptosis, clonal deletion, receptor editing or anergy to avoid autoimmunity. The specific contribution of apoptosis to normal B cell development and self-tolerance is incompletely understood. Here, we quantify self-reactivity, polyreactivity and apoptosis during physiologic B lymphocyte development. Self-reactivity and polyreactivity are most abundant in early immature B cells and diminish significantly during maturation within the bone marrow. Minimal apoptosis still occurs at this site, however B cell receptors cloned from apoptotic B cells show comparable self-reactivity to that of viable cells. Apoptosis increases dramatically only following immature B cells leaving the bone marrow sinusoids, but above 90% of cloned apoptotic transitional B cells are not self-reactive/polyreactive. Our data suggests that an apoptosis-independent mechanism, such as receptor editing, removes most self-reactive B cells in the bone marrow. Mechanistically, lack of survival signaling rather than clonal deletion appears to be the underpinning cause of apoptosis in most transitional B cells in the periphery.

Cross-linked Triblock Peptide Capsules as Potential Oxygen Carriers.

Perfluorodecalin (PFD)-filled capsules have been studied for over 15 years as artificial oxygen carriers. However, none of these capsules combines good biocompatibility, good mechanical stability and dispersion stability. Here we propose to use synthetic triblock peptides containing a central block of cysteine units as a cross-linking shell material for capsules with both good biocompatibility and stability. Together with outer aspartate units and inner phenylalanine units, the resulting amphiphilic triblock peptides can encapsulate PFD efficiently to prepare capsules with a suitable diameter, a certain mechanical strength, a large diffusion constant, fast gas exchange rates, and little cytotoxicity. Given the above advantages, these PFD-filled peptide capsules are very promising as potential artificial oxygen carriers.

CD40 Drives Central Nervous System Autoimmune Disease by Inducing Complementary Effector Programs via B Cells and Dendritic Cells.

Costimulatory CD40 plays an essential role in autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis (MS). However, how CD40 drives autoimmune disease pathogenesis is not well defined. Here, we used a conditional knockout approach to determine how CD40 orchestrates a CNS autoimmune disease induced by recombinant human myelin oligodendrocyte glycoprotein (rhMOG). We found that deletion of CD40 in either dendritic cells (DCs) or B cells profoundly reduced EAE disease pathogenesis. Mechanistically, CD40 expression on DCs was required for priming pathogenic Th cells in peripheral draining lymph nodes and promoting their appearance in the CNS. By contrast, B cell CD40 was essential for class-switched MOG-specific Ab production, which played a crucial role in disease pathogenesis. In fact, passive transfer of MOG-immune serum or IgG into mice lacking CD40 on B cells but not DCs reconstituted autoimmune disease, which was associated with inundation of the spinal cord parenchyma by Ig and complement. These data demonstrate that CD40 supports distinct effector programs in B cells and DCs that converge to drive a CNS autoimmune disease and identify targets for intervention.

Bacterial urinary tract infection and subclinical bacteriuria in dogs receiving antineoplastic chemotherapy.

BACKGROUND: Immunosuppressive treatment with glucocorticoids and cyclosporine increases the risk for positive urine cultures (PUCs) in dogs. OBJECTIVE: To investigate the prevalence and incidence of PUC in dogs diagnosed with cancer and treated with antineoplastic chemotherapy while distinguishing between subclinical bacteriuria (SB) and urinary tract infection (UTI). ANIMALS: Forty-six client-owned dogs with nonurogenital cancer treated with antineoplastic chemotherapy. METHODS: Prospective observational longitudinal clinical study. Dogs in which a urine culture was performed before the start of and at least once during antineoplastic chemotherapy were included. A McNemar's test was used to investigate if the prevalence of PUC increased during antineoplastic chemotherapy. Positive urine cultures were categorized into SB and UTI and multiple PUCs from the same dog and category were grouped together as 1 episode of PUC. RESULTS: Urine culture was positive in 21/185 urine samples in 8/46 dogs. Antineoplastic chemotherapy did not influence the prevalence of PUC (P = 1.00), which was 11% (5/46 dogs; 95% confidence interval: 5-23%) before the start of and 13% (6/46 dogs; 95% confidence interval: 6-26%) during antineoplastic chemotherapy. Eight dogs had 10 episodes of PUC; 7/10 episodes were classified as SB, and in 3/10 episodes UTI (chronic prostatitis, prostatic abscess, and emphysematous cystitis) was diagnosed. Escherichia coli was the most common pathogen, isolated in 9/10 episodes. CONCLUSIONS AND CLINICAL IMPORTANCE: We did not find evidence that antineoplastic chemotherapy is a major predisposing factor for the development of PUC. Most dogs with PUC had SB.

Syntheses of Polypeptides and Their Biomedical Application for Anti-Tumor Drug Delivery.

Polypeptides have attracted considerable attention in recent decades due to their inherent biodegradability and biocompatibility. This mini-review focuses on various ways to synthesize polypeptides, as well as on their biomedical applications as anti-tumor drug carriers over the past five years. Various approaches to preparing polypeptides are summarized, including solid phase peptide synthesis, recombinant DNA techniques, and the polymerization of activated amino acid monomers. More details on the polymerization of specifically activated amino acid monomers, such as amino acid N-carboxyanhydrides (NCAs), amino acid N-thiocarboxyanhydrides (NTAs), and N-phenoxycarbonyl amino acids (NPCs), are introduced. Some stimuli-responsive polypeptide-based drug delivery systems that can undergo different transitions, including stability, surface, and size transition, to realize a better anti-tumor effect, are elaborated upon. Finally, the challenges and opportunities in this field are briefly discussed.

Green Textile Materials for Surface Enhanced Raman Spectroscopy Identification of Pesticides Using a Raman Handheld Spectrometer for In-Field Detection.

Surface enhanced Raman spectroscopy (SERS) has evolved into a powerful analytical method in food and environmental analytical sciences due to its high sensitivity. Pesticide analysis is a major discipline therein. Using sustainable materials has become increasingly important to adhere to Green Chemistry principles. Hence, the green textiles poly-(L-lactic acid) (PLA) and the mixed fabric polyethylene terephthalate polyamide (PET/PA) were investigated for their applicability as solid supports for gold nanoparticles to yield SERS substrates. Gold nanoparticle solutions and green textile supports were prepared after preparation optimization. Particle size, dispersity, and particle distribution over the textiles were characterized by absorption spectroscopy and transmission electron imaging. The performance of the SERS substrates was tested using the three pesticides imidacloprid, paraquat, and thiram and a handheld Raman spectrometer with a laser wavelength of 785 nm. The resulting SERS spectra possessed an intra-substrate variation of 7-8% in terms of the residual standard deviation. The inter-substrate variations amounted to 15% for PET/PA and to 27% for PLA. Substrate background signals were smaller with PLA but more enhanced through PET/PA. The pesticides could be detected at 1 pg on PET/PA and at 3 ng on PLA. Hence, PET/PA woven textile soaked with gold nanoparticle solution provides green SERS substrates and might prove, in combination with fieldable Raman spectrometers, suitable for in-field analytics for pesticide identification.

THE NOVEL USE OF HIGH-FLOW POLYIMIDE CANNULAS TO IMPROVE SILICONE OIL INJECTABILITY IN VITREORETINAL SURGERY.

PURPOSE: The injection of high-viscosity silicone oil lengthens injection time. New polyimide cannulas offer a greater inner diameter than conventional metal cannulas at the same gauge. We compared the injection time for polyimide and metal cannulas at 23 G for a variety of silicone oils including a 12,500-mPas prototype oil. METHODS: In this laboratory study, injection time was measured three times per cannula and per oil. Warming the oil before injection to up to 42°C was also evaluated. Finally, the feasibility of polyimide cannulas was tested in vitrectomized porcine eyes. RESULTS: The 23-G polyimide cannula mostly decreased injection times. The time to inject 5 mL of Siluron Xtra and Siluron 5000 decreased by 6:02 (76.9%) minutes (483 vs. 121 seconds) and 12:01 (74.7%) minutes (973 vs. 252 seconds), respectively. Although the 23-G metal cannula failed to inject 12,500 mPas oil, 5 mL was injected in 10:21 minutes using the polyimide cannula. Prewarming Siluron 5000 to 42°C lowered the injection time by 9.0% and by 12.1% when using the metal or polyimide cannula, respectively. CONCLUSION: Polyimide cannulas allow a clinically relevant decrease in injection time. They may not only shorten surgery time but could also ease the use of next-generation ultra-high-viscosity silicone oils. Prewarming silicone oil leads to decreased injection times.

Presbyopia correction after previous Intracor treatment: Combined implantation of a small-aperture and a non-diffractive extended-depth-of-focus lens.

PURPOSE: We present the case of implantation of two different Extended depth of focus intraocular lenses (EDoF IOLs) in a patient with a history of unilateral intrastromal femtosecond laser treatment for presbyopia correction (Intracor). OBSERVATIONS: The patient reported decreasing visual acuity at near distance and increasing spectacle dependence. Ten years earlier, he had Intracor treatment for presbyopia correction in his left eye. Corrected distance visual acuity (CDVA) was 0.08 logMAR for the right eye and 0.16 logMAR for the left eye. Apart from dysfunctional lens syndrome, the examination results were unremarkable. Phacoemulsification and subsequent IOL implantation was performed in both eyes. The left eye was implanted with an IC-8 (AcuFocus, Irvine, CA, USA), whereas the fellow eye was implanted with an AcrySof IQ Vivity IOL (Alcon, Fort Worth, TX, USA). Postoperatively, CDVA improved to 0.02 and 0.04 logMAR for the right and left eye. Uncorrected intermediate visual acuity (UIVA) was 0.24 logMAR for the right eye and -0.04 logMAR for the left eye, binocular UIVA was -0.04 logMAR. The patient reported a low level of photic phenomena and spectacle independence for far and intermediate distance. CONCLUSIONS AND IMPORTANCE: Combined implantation of a non-diffractive and a small-aperture EDoF lens after previous unilateral Intracor treatment could successfully improve visual acuity at far and intermediate distance.

Diagnostic imaging techniques in patient with liquefied aftercataract imitating intraocular lens opacification.

An 81-year-old patient was referred for an intraocular lens (IOL) exchange surgery because of a presumed IOL opacification. Using diagnostic imaging techniques such as anterior segment optical coherence tomography (OCT) and Scheimpflug imaging, we revealed that the presumed IOL opacification was in fact a liquefied aftercataract. As a result, an intraocular surgery was avoided and the patient was successfully treated with a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy.

Physicochemical Properties of Explanted Silicone Oil After Use as an Intraocular Tamponade.

PURPOSE: We studied the effects of exposure to biological media within the eye, such as contamination with lipophilic and amphiphilic substances, on the physicochemical parameters of silicone oil used as an intraocular tamponade. METHODS: We removed silicone oil with visible emulsification from 15 patients and measured each sample for shear viscosity and surface tension. We induced in vitro emulsification with balanced salt solution. Using the zeta-potential, we evaluated the emulsion droplet's electrochemical stability. We repeated all experiments in a control group of unused oil. Electrochemical stability and viscosity were additionally measured in oils with high-molecular-weight components. RESULTS: We recovered silicone oils implanted between 30 and 506 days (mean, 196 days). Viscosity did not differ between explanted and control groups. Surface tension and zeta potential remained unchanged (P = 0.61 and P = 0.84, respectively). All oils showed a significant correlation of viscosity with temperature (P < 0.01 for all). Oils with added high-molecular-weight components showed a lower emulsion stability. CONCLUSIONS: Prolonged contact to hydrophilic biological media does not alter high-viscosity silicone oil's physicochemical parameters. During typical durations of intraocular use, lipophilic and amphiphilic molecules had no deleterious effect. The addition of high-molecular-weight components might decrease the silicone oil's electrochemical emulsion stability, possibly easing the confluence of emulsion droplets. TRANSLATIONAL RELEVANCE: Although the physicochemical parameters of silicone oils are not altered after clinically relevant durations within the eye, emulsion stability significantly differs between oil types.

Laboratory and Clinical Experience With a Diffractive Trifocal Intraocular Lens Sutured to an Artificial Iris.

PURPOSE: To determine in vitro, using a translational research approach before realizing the procedure in a patient with iatrogenic aphakia and partial aniridia, whether suturing a trifocal intraocular lens (IOL) to an artificial iris degrades the IOL's optical quality. METHODS: Optical quality was analyzed by measuring the modulation transfer function (MTF) at a 3-mm aperture and at 50 and 100 lp/mm spatial frequencies. The FineVision Pod F GF IOL (PhysIOL) was assessed in two powers: two +20.00 diopters (D) (20A and 20B IOLs) and two +30.00 D (30A and 30B IOLs). The IOLs' decentration in relation to the artificial iris's center was evaluated. The laboratory results provided empirical evidence in the informed consent for surgical intervention in a patient with iatrogenic aphakia and iris defect in one eye. Clinical results were measured using the parameter of corrected distance visual acuity plus a patient self-assessment of the cosmetic appearance of the operated eye. RESULTS: The 20A and 20B IOLs demonstrated a mean MTF reduction of up to 1.1%, whereas the 30A and 30B IOLs showed a decrease of up to 5.2% for both spatial frequencies. All lenses showed good centration levels. In the clinical case, the patient showed corrected distance visual acuity, distance-corrected near visual acuity, and distance-corrected intermediate visual acuity of 0.20, 0.20, and 0.22 logMAR, respectively. The patient was satisfied with the cosmetic outcome. CONCLUSIONS: There was merely a slight reduction in trifocal IOL optical quality after it was sutured to an artificial iris. Clinically, the combined implantation of the artificial iris and FineVision IOL provided good functional and cosmetic outcomes. [J Refract Surg. 2022;38(1):61-68.].

[Fixation of an intraocular lens using reverse optic capture with haptic tuck for intraoperative posterior capsule rupture]. / Fixation einer Intraokularlinse bei intraoperativem Hinterkapseldefekt durch Einklemmen der Linsenoptik in der vorderen Kapsulorhexis.

Exact positioning and optimal axial alignment are mandatory to achieve satisfactory postoperative refractive results after implantation of a toric or presbyopia correcting intraocular lens (IOL). Posterior capsule rupture can preclude stable capsular fixation. In such cases, reverse optic capture with haptic tuck results in stable fixation of the lens with respect to centering, rotation and axial position. Only the haptics are positioned in the capsule, behind the anterior capsulorrhexis. The optic remains in the sulcus; thus, the lens is fixed in the rhexis, providing long-term stability despite the presence of posterior capsule rupture.

Bilateral Artificial Iris implantation in patients with bilateral iris defects.

PURPOSE: Binocular traumatic or atraumatic iris defects can lead to an increased sensitivity to glare and cosmetic disfigurement. Surgical iris reconstruction is one approach to alleviate these problems. We report the clinical outcomes after medically indicated bilateral implantation of an Artificial Iris prosthesis in three patients with binocular iris defects with different etiologies. OBSERVATIONS: All three patients underwent binocular CUSTOMFLEX ArtificialIris (AI) (HumanOptics AG, Erlangen, Germany) implantation with simultaneous cataract surgery. Corrected distance visual acuity (CDVA), manifest refraction, Contrast sensitivity, endothelial cell density and subjective visual impairment as well as subjective cosmetic disfigurement were measured pre- and postoperatively. CDVA remained stable or improved in all three patients. We observed an increase in contrast sensitivity and reduction of glare sensitivity in two patients. All patients reported satisfaction with the cosmetical result after the implantation. CONCLUSIONS AND IMPORTANCE: The bilateral Artificial Iris implantation is an effective therapeutic option to reduce glare sensitivity and to achieve an aesthetically pleasing result also in selected patients with binocular traumatic or atraumatic iris defects.

"Double Prosthesis Implantation": Biometry and Refractive Outcomes in Combined Intraocular Lens and Artificial Iris Surgery.

PURPOSE: To assess the biometry and postoperative refraction in iris repair using ArtificialIris in combination with an intraocular lens (IOL). SETTING: Department of Ophthalmology, University Hospital Heidelberg, University of Heidelberg, Germany. DESIGN: Retrospective observational study. METHODS: We included 44 aniridic and aphakic eyes for IOL implantation in combination with iris prosthesis reconstruction. The iris prostheses were either sutured into the ciliary sulcus and fixed by transscleral suturing or were implanted together with a capsular tension ring and the IOL in the capsular bag. The primary outcomes measured were pre- and postoperative best corrected visual acuity (CDVA), objective and subjective refraction, anterior chamber depth and optical biometry comparing common IOL formulae. RESULTS: Reasons for surgery were trauma (39 eyes), iatrogenic causes (1 eye), aniridic state after severe iritis (2 eyes) or iris tumor (2 eyes). Monocular CDVA improved significantly (p<0.0001) from median 0.55 logMAR (0.0 to 1.98) to 0.16 logMAR (-0.08 to 2.0). There were no significant differences between the postoperative target refraction calculated by the formulae "Haigis", "Hoffer-Q", "SRK/T" and "Holladay 1" (p=0.68). The absolute deviation from target refraction did not differ significantly between the formulae (p=0.87). Median target refraction was -0.42 D (-4.0 to 1.68). Postoperatively median spherical equivalent was 0.00 D (-5.38 to 2.38). Median absolute deviation from target refraction after 5 months of follow-up was 0.98 D (0.06 to 5.17). CONCLUSION: Postoperative refraction using common techniques and using preoperative biometry revealed a well predictable postoperative refraction. There is no correction factor needed.

Capsules from synthetic diblock-peptides as potential artificial oxygen carriers.

The design of an encapsulation system consisting of a synthetic peptide which is fully biodegradable into non-toxic constituents. This system should be capable of encapsulating perfluorinated hydrocarbons and should be a promising basis for oxygen carriers to be used as artificial blood replacement. A diblock-peptide is synthesised following a phosgene-free method and characterised by 1H-NMR. Subsequently, this diblock-peptide is self-assembled with perfluorodecalin (PFD) to form PFD-filled capsules as potential artificial oxygen carriers allowing for rapid oxygen uptake and release. The diblock-peptide Bu-PAsp10-PPhe10 is successfully synthesised and used to encapsulate PFD. The capsules have a spherical shape with an average diameter of 360 nm in stable aqueous dispersion. NMR measurements prove their physical capability for reversible uptake and release of oxygen. The resulting capsules are expected to be fully biodegradable and possibly could act as oxygen carriers for artificial blood replacement.

Histomorphology and Immunohistochemistry of a Congenital Nephromegaly Demonstrate Concurrent Features of Heritable and Acquired Cystic Nephropathies in a Girgentana Goat (Capra falconeri).

Polycystic kidney diseases (PKD) represent frequent congenital and adult nephropathies in humans and domestic animals. This report illustrates an uncommon state of congenital PKD in a girgentana goat (Capra falconeri). A stillborn female goat kid was submitted for postmortem examination and underwent macroscopic and microscopic examination. The kidneys showed a bilateral nephromegaly and a perpendicular polycystic altered texture of the renal parenchyma. Renal tissue sections were comprehensively investigated by histopathology (overview and special stains), immunohistochemistry (CD10, CD117, pan-cytokeratin, cytokeratin 7, E-cadherin, Pax2, Pax8, and vimentin), and electron microscopy (SEM, TEM). Histopathology of renal tissue sections revealed polycystic alterations of the renal parenchyma as well as conspicuous polypoid proliferates/projections of the renal tubular epithelium, which showed clear cell characteristics. Furthermore, epithelial projections were indicative for epithelio-mesenchymal-transition, cellular depolarization, and strong expression of differentiation markers Pax2, Pax8, and CD10. Ultrastructural morphology of the projections was characterized by numerous diffusely distributed, demarked round cytoplasmic structures and several apico-lateral differentiations. Additionally, hepatic malformations comprising biliary duct proliferation with saccular dilation and bridging fibrosis were observed. Notably, this report describes the first case of a congenital cystic nephropathy with overlapping features of heritable and acquired nephropathies in any species. Epithelio-mesenchymal-transition and altered cadherin expression seem to be crucial components of a suspected pathomechanism during cystogenesis.

Reasons for explantation of phakic intraocular lenses and associated perioperative complications: cross-sectional explant registry analysis.

BACKGROUND: We discuss the safety, since their introduction, of phakic intraocular lenses (pIOLs) to correct refractive errors in healthy eyes. We investigated the reasons for pIOL explantation and the associated perioperative complications. METHODS: This retrospective, cross-sectional study included 69 pIOLs, explanted at a single tertiary center between July 2005 and March 2020: 34 angle-supported (G1), 28 iris-fixated (G2) and seven posterior chamber (G3) pIOLs. Case data including the reason for explantation was taken from the patient records. Intra- and postoperative complications were evaluated for an association with the pIOL. RESULTS: The mean duration in the eye was 10.4 (0.2-28) years. Cataractogenesis and subsequent surgery that required pIOL explantation was the reason in 42% of all cases. In 22%, cataract in combination with endothelial damage prompted explantation, with 26, 18 and 14% for G1, G2 and G3 respectively. The second most common reasons were corneal damage alone in the angle-supported group (26%), IOL subluxation in the iris-fixated group (18%), and photopic disturbance in the posterior chamber group (29%). In 68% of all explantations, the surgical course was unremarkable, while in the remaining cases perioperative complications were associated with the lens in 45.7%. CONCLUSION: Overall, the need for cataract surgery was the most common reason for pIOL explantation. Corneal complications were more frequent in the angle-supported pIOLs and their removal was associated with higher rates of complication compared to the other groups.