A pilot study of evaluation of semi-rigid and flexible catheters for less invasive surfactant administration in preterm infants with respiratory distress syndrome-a randomized controlled trial.

BACKGROUND: In respiratory distress syndrome, many neonatology centers worldwide perform minimal invasive surfactant application in premature infants, using small-diameter catheters for endotracheal intubation and surfactant administration. METHODS: In this single-center, open-label, randomized-controlled trial, preterm infants requiring surfactant administration after birth, using a standardized minimal invasive protocol, were randomized to two different modes of endotracheal catheterization: Flexible charrière-4 feeding tube inserted using Magill forceps (group 1) and semi-rigid catheter (group 2). Primary outcome was duration of laryngoscopy. Secondary outcomes were complication rate (intraventricular hemorrhage, soft-tissue damage in first week of life) and vital parameters during laryngoscopy. Between 2019 and 2020, 31 infants were included in the study. Prior to in-vivo testing, laryngoscopy durations were studied on a neonatal airway mannequin in students, nurses and doctors. RESULTS: Mean gestational age and birth weight were 27 + 6/7 weeks and 1009 g; and 28 + 0/7 weeks and 1127 g for group 1 and 2, respectively. Length of laryngoscopy was similar in both groups (61.1 s and 64.9 s) overall (p.77) and adjusted for weight (p.70) or gestational age (p.95). Laryngoscopy failed seven times in group 1 (43.8%) and four times (26.7%) in group 2 (p.46). Longer laryngoscopy was associated with lower oxygen saturation with lowest levels occurring after failed laryngoscopy attempts. Secondary outcomes were similar in both groups. In vitro data on 40 students, 40 nurses and 12 neonatologists showed significant faster laryngoscopy in students and nurses group 2 (p < .0001) unlike in neonatologists (p.13). CONCLUSION: This study showed no difference in laryngoscopy duration in endotracheal catheterization when comparing semi-rigid and flexible catheters for minimal invasive surfactant application in preterm infants. In accordance with preliminary data and in contrast to published in-vitro trials, experienced neonatologists were able to perform endotracheal catheterization using both semi-rigid and flexible catheters at similar rates and ease, in vitro and in vivo. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05024435 Registered 27 August 2021-Retrospectively registered.

Endothelial cell density and corneal graft thickness following excimer laser vs. femtosecond laser-assisted penetrating keratoplasty-a prospective randomized study.

PURPOSE: The study aims to compare the impact of non-mechanical excimer laser-assisted (EXCIMER) and femtosecond laser-assisted (FEMTO) trephinations on graft endothelial cell density (ECD) and graft thickness before and after suture removal following penetrating keratoplasty (PK). METHODS: The inclusion criteria for this prospective, randomized, clinical study were as follows: (1) surgeries performed by one surgeon; (2) primary central PK; (3) keratoconus (KC) or Fuchs' dystrophy (FUCHS); (4) no previous intraocular surgery; (5) graft oversize, 0.1 mm; and (6) 16-bite double-running suture. In 68 eyes of 68 patients (mean age: 53.3 ± 19.8 years), PK was performed using either 193-nm MEL70 excimer laser ("EXCIMER": 17 KC, 18 FUCHS) or 60-KHz femtosecond laser ("FEMTO": 17 KC, 16 FUCHS) trephination. Specular microscopy (EM 3000) and pachymetry (EM 3000; Pentacam HR; Casia SS-1000) were performed before removing the first suture (11.4 ± 1.9 months) and after removing the second suture (22.6 ± 3.8 months), but before any additional ophthalmic surgery. RESULTS: ECD did not differ significantly (P ≥ 0.436) between EXCIMER and FEMTO either with "all-sutures-in" (1887 ± 409 vs. 1886 ± 438) or with "all-sutures-out" (1703 ± 379 vs. 1737 ± 362). Central corneal thickness and corneal thickness at the thinnest point of the cornea did not differ significantly between EXCIMER and FEMTO either with all-sutures-in (P ≥ 0.096 and P ≥ 0.653) or with all-sutures-out (P ≥ 0.636 and P ≥ 0.717). CONCLUSIONS: EXCIMER and FEMTO trephinations from the epithelial side seem to have no disadvantages regarding endothelial cell loss after PK, and both surgical procedures are safe for the endothelium. A larger sample size and longer follow-up are needed to evaluate the long-term impact of EXCIMER and FEMTO trephinations on ECD.

Confocal microscopy as an early relapse marker for acanthamoeba keratitis.

Acanthameoba keratitis is a serious ophthalmological condition with a potentially vision-threatening prognosis. Early diagnosis and recognition of relapse, and the detection of persistent Acanthamoeba cysts, are essential for informing the prognosis and managing the condition. We suggest the use of in vivo confocal microscopy not only to identify the early signs of relapse after keratoplasty in patients with Acanthamoeba keratitis, but also as an additional follow-up tool after antimicrobial crosslinking. This study shows that in vivo confocal microscopy is, in experienced hands, a quick and reliable diagnostic tool. Clin. Anat. 31:60-63, 2018. © 2017 Wiley Periodicals, Inc.

Crosslinking and corneal cryotherapy in acanthamoeba keratitis -- a histological study.

PURPOSE: Acanthamoeba keratitis is rare, but difficult to treat. Penetrating keratoplasty is performed in therapy-resistant cases. Nevertheless, subsequent recurrences occur in 40 % of the cases. In addition to triple-topical therapy (polyhexamid, propamidinisoethionat, neomycin), treatment alternatives are corneal cryotherapy and/or crosslinking (CXL). The aim of our present histological study was to analyze the persistence of acanthamoebatrophozoites and cysts, the persistence of bacteria, and activation of keratocytes in corneas of acanthamoeba keratitis patients following corneal cryotherapy and/or CXL. PATIENTS AND METHODS: We analyzed histologically corneal buttons (from penetrating keratoplasties) of nine patients with acanthamoeba keratitis, following corneal cryotherapy (two patients) or a combination of crosslinking and corneal cryotherapy (seven patients), using haematoxilin­eosin, periodic acid Schiff (PAS), Gram and alpha-smooth muscle actin (alpha-SMA) stainings. RESULTS: Acanthamoeba trophozoites persisted in three corneas after cryotherapy and CXL. Cysts persisted in one of two corneas following corneal cryotherapy and in six of seven corneas after a combination of CXL and cryotherapy. One cornea showed positive Gram staining, but there were no alpha-SMA positive keratocytes in any of the corneas. CONCLUSIONS: Crosslinking and corneal cryotherapy have only limited impact on killing of acanthamoeba trophozoites, cysts, or bacteria. Corneal cryotherapy and CXL did not stimulate myofibroblastic transformation of keratocytes.

Anhydrous Amorphous Calcium Oxalate Nanoparticles from Ionic Liquids: Stable Crystallization Intermediates in the Formation of Whewellite.

The mechanisms by which amorphous intermediates transform into crystalline materials are not well understood. To test the viability and the limits of the classical crystallization, new model systems for crystallization are needed. With a view to elucidating the formation of an amorphous precursor and its subsequent crystallization, the crystallization of calcium oxalate, a biomineral widely occurring in plants, is investigated. Amorphous calcium oxalate (ACO) precipitated from an aqueous solution is described as a hydrated metastable phase, as often observed during low-temperature inorganic synthesis and biomineralization. In the presence of water, ACO rapidly transforms into hydrated whewellite (monohydrate, CaC2 O4 ⋅H2 O, COM). The problem of fast crystallization kinetics is circumvented by synthesizing anhydrous ACO from a pure ionic liquid (IL-ACO) for the first time. IL-ACO is stable in the absence of water at ambient temperature. It is obtained as well-defined, non-agglomerated particles with diameters of 15-20 nm. When exposed to water, it crystallizes to give (hydrated) COM through a dissolution/recrystallization mechanism.

Early evaluation of corneal collagen crosslinking in ex-vivo human corneas using two-photon imaging.

The clinical outcome of corneal collagen crosslinking (CXL) is typically evaluated several weeks after treatment. An earlier assessment of its outcome could lead to an optimization of the treatment, including an immediate re-intervention in case of failure, thereby, avoiding additional discomfort and pain to the patient. In this study, we propose two-photon imaging (TPI) as an earlier evaluation method. CXL was performed in human corneas by application of riboflavin followed by UVA irradiation. Autofluorescence (AF) intensity and lifetime images were acquired using a commercial clinically certified multiphoton tomograph prior to CXL and after 2h, 24h, 72h, and 144h storage in culture medium. The first monitoring point was determined as the minimum time required for riboflavin clearance from the cornea. As control, untreated samples and samples treated only with riboflavin (without UVA irradiation) were monitored at the same time points. Significant increases in the stroma AF intensity and lifetime were observed as soon as 2h after treatment. A depth-dependent TPI analysis showed higher AF lifetimes anteriorly corresponding to areas were CXL was most effective. No alterations were observed in the control groups. Using TPI, the outcome of CXL can be assessed non-invasively and label-free much sooner than with conventional clinical devices.

Ultrastructural findings in graft failure after Descemet membrane endothelial keratoplasty (DMEK) and new triple procedure.

To investigate factors that influence graft failure after Descemet membrane endothelial keratoplasty (DMEK) based on transmission electron microscopy results.Retrospective observational case series.This single center study included 16 eyes of 16 patients with penetrating keratoplasty (n = 14) or repeat DMEK (n = 2) following graft failure after DMEK. The main outcome measures were ultrastructural changes in the explanted graft on transmission electron microscopy, best-corrected visual acuity, and central corneal thickness.The mean preoperative and postoperative best-corrected visual acuity was 1.01 ±â€Š0.54 logMAR and 0.56 ±â€Š0.37 logMAR. The mean central corneal preoperative and postoperative thickness was 667 ±â€Š187 µm and 511 ±â€Š42 µm. Visual acuity and central corneal thickness improved significantly (P = .001/P = .003) after repeat surgery. Electron microscopy showed that 3 of 14 corneas showed upside down transplantation, and 3 corneas had pigmented cells or pigment granules at the Descemet-stroma interface. Further, 9 of 16 specimens showed a posterior collagenous layer deposited onto the Descemet membrane (average thickness 5.1 ±â€Š6.2 µm; ranged 0.65-20 µm); this did not correlate significantly with the time between the original and repeat keratoplasty. Of 16 original grafts, 7 showed ultrastructural anomalies of the Descemet membrane, but one excised cornea showed no Descemet membrane pathologies.The majority of eyes with graft failure after DMEK showed ultrastructural changes in the Descemet membrane. It is crucial to assess donor tissue quality and to conduct graft marking before surgery to avoid immediate or delayed graft failure after DMEK. Nevertheless, repeat keratoplasty provided significant improvement in central corneal thickness and visual acuity.

Reactive uveitis, retinal vasculitis and scleritis as ocular end-stage of Acanthamoeba keratitis: a histological study.

We analysed histologically two Acanthamoeba keratitis (AK) eyes with anterior and posterior segment inflammation and blindness. Two enucleated eyes of 2 patients (age 45 and 51y) with AK (PCR of epithelial abrasion positive) were analysed. Histological analysis was performed using hematoxylin-eosin, periodic acid-Schiff and Gömöri-methenamine silver staining. We could not observe Acanthamoeba trophozoites or cysts neither in the cornea nor in other ocular tissues. Meanwhile, we found uveitis, retinal vasculitis and scleritis in these eyes, due to the long-standing, recalcitrant AK. So in this stage of AK, systemic immune suppression may be necessary for a longer time period.

Reconsidering Sequential Double Running Suture Removal After Penetrating Keratoplasty: A Prospective Randomized Study Comparing Excimer Laser and Motor Trephination.

PURPOSE: We assessed the impact of sequential double running suture removal on corneal curvature after penetrating keratoplasty (PK), comparing mechanical and nonmechanical excimer laser trephination. METHODS: PK was performed in 134 patients (mean age 51 ± 18 yrs) using either the excimer laser [excimer, n = 60 (37 keratoconus and 23 Fuchs dystrophy)] or motor trephination [control, n = 74 (44 keratoconus and 30 Fuchs dystrophy)] and a double running cross-stitch suture. Refractometry, Zeiss keratometry, and Tomey corneal topography were performed before removal of the first suture (15.2 ± 4.2 mo) and immediately before and at least 6 weeks after removal of the second suture (21.4 ± 5.6 mo). RESULTS: Keratometry before removal of the first (-1.7 ± 2.3 D vs. -3.1 ± 2.8 D) and second (-2.3 ± 2.6 D vs. -3.8 ± 2.8 D) sutures showed that the change in the corneal base curve was significantly smaller in the excimer group than the control group (P < 0.004). After complete suture removal, astigmatism decreased in 52% and 11%, remained stable (±0.5 D) in 27% and 9%, and increased in 21% and 80% of eyes in the excimer and control groups, respectively, resulting in significantly lower astigmatism in the excimer (3.1 ± 2.1 D) group compared with the control group (6.2 ± 2.9 D) with "all-sutures-out" (P < 0.0001). The change in vector-corrected astigmatism (Jaffe) was significantly smaller in the excimer group (4.3 ± 3.5 D) than in the control group (6.9 ± 4.5 D; P < 0.001). CONCLUSIONS: In conclusion, less change in astigmatism and the base curve after sequential removal of a double running suture indicates better alignment of the graft in the recipient bed after excimer laser trephination. After double running suture removal, astigmatism decreases or remains unchanged in 79% of patients after excimer laser keratoplasty and increases in 80% of patients after conventional motor trephination.

Assessment of Human Corneas Prior to Transplantation Using High-Resolution Two-Photon Imaging.

Purpose: The purpose of this study was to evaluate the feasibility of using two-photon imaging (TPI) to assess the condition of human corneas for transplantation. Methods: Human corneas were imaged after different storage times: short-term (STS), medium-term (MTS), and long-term (LTS) storage. A high-resolution, custom-built 5-dimensional multiphoton microscope with 12-fs pulsed laser excitation was used for image acquisition. Results: Optical discrimination between different corneal layers and sublayers based on their morphologic characteristics revealed by two-photon autofluorescence (AF) is possible. Furthermore, all layers were characterized based on AF lifetimes to gain information on metabolic activities of cells. The NAD(P)H free to protein-bound ratio (a1/a2) of epithelial cells increased significantly in both MTS and LTS corneas compared with STS corneas. In endothelial cells, NAD(P)H a1/a2 was significantly increased in MTS samples. For keratocytes, the NAD(P)H a1/a2 decreased significantly with storage time. This could indicate that the metabolic activity of the epithelial and endothelial cells reduces, whereas the activity of keratocytes increases with storage time. The analysis of the stroma SHG images indicated that the organization of collagen fibers decreases with storage time. The feasibility of measuring the endothelial cell density (ECD) using TPI was demonstrated. An ECD of 1461 ± 190 cells/mm2 was obtained for MTS samples based on TPI. Conclusions: TPI can provide information not accessible by current clinical methods, such as the cells' metabolic state and structural organization of the stroma, with subcellular resolution. Thus, it may improve the screening process of corneas prior to transplantation and might help to optimize the storage conditions.

High-resolution, label-free two-photon imaging of diseased human corneas.

The diagnosis of corneal diseases may be improved by monitoring the metabolism of cells and the structural organization of the stroma using two-photon imaging (TPI). We used TPI to assess the differences between nonpathological (NP) human corneas and corneas diagnosed with either keratoconus, Acanthamoeba keratitis, or stromal corneal scars. Images were acquired using a custom-built five-dimensional laser-scanning microscope with a broadband sub-15 femtosecond near-infrared pulsed excitation laser and a 16-channel photomultiplier tube detector in combination with a time-correlated single photon counting module. Morphological alterations of epithelial cells were observed for all pathologies. Moreover, diseased corneas showed alterations to the cells' metabolism that were revealed using the NAD(P)H free to protein-bound ratios. The mean autofluorescence lifetime of the stroma and the organization of the collagen fibers were also significantly altered due to the pathologies. We demonstrate that TPI can be used to distinguish between NP and diseased human corneas, based not only on alterations of the cells' morphology, which can also be evaluated using current clinical devices, but on additional morphological and functional features such as the organization of the stroma and the cells' metabolism. Therefore, TPI could become an efficient tool for diagnosing corneal diseases and better understanding the biological processes of the diseases.

Intraocular juvenile xanthogranuloma of the iris in an adult patient.

PURPOSE: Juvenile xanthogranuloma (JXG) is a rare histiocytic skin disease primarily of young children, which may also affect ocular structures and in particular the iris. OBSERVATIONS: This is a case report of a fifty-year-old patient without skin lesions showing a progressive decrease of visual acuity, iris vascularization and a yellowish iris tumor in the iridocorneal angle of his right eye. Treatment with topical and systemic prednisolone led to full recovery of visual acuity, tumor regression and restitutio ad integrum. CONCLUSIONS AND IMPORTANCE: Although the juvenile xanthogranuloma is a very rare skin disease of young children, it may also affect the eye and in particular the iris in adult patients. There exists no standard treatment, the first-line therapy in most cases, however, is topical and systemic prednisolone application.

Penetrating Keratoplasty for Keratoconus - Excimer Versus Femtosecond Laser Trephination.

BACKGROUND: In case of keratoconus, rigid gas-permeable contact lenses as the correction method of first choice allow for a good visual acuity for quite some time. In a severe stage of the disease with major cone-shaped protrusion of the cornea, even specially designed keratoconus contact lenses are no more tolerated. In case of existing contraindications for intrastromal ring segments, corneal transplantation typically has a very good prognosis. METHODS: In case of advanced keratoconus - especially after corneal hydrops due to rupture of Descemet's membrane - penetrating keratoplasty (PKP) still is the surgical method of first choice. Noncontact excimer laser trephination seems to be especially beneficial for eyes with iatrogenic keratectasia after LASIK and those with repeat grafts in case of "keratoconus recurrences" due to small grafts with thin host cornea. For donor trephination from the epithelial side, an artificial chamber is used. Wound closure is achieved with a double running cross-stitch suture according to Hoffmann. Graft size is adapted individually depending on corneal size ("as large as possible - as small as necessary"). Limbal centration will be preferred intraoperatively due to optical displacement of the pupil. During the last 10 years femtosecond laser trephination has been introduced from the USA as a potentially advantageous approach. RESULTS: Prospective clinical studies have shown that the technique of non-contact excimer laser PKP improves donor and recipient centration, reduces "vertical tilt" and "horizontal torsion" of the graft in the recipient bed, thus resulting in significantly less "all-sutures-out" keratometric astigmatism (2.8 vs. 5.7 D), higher regularity of the topography (SRI 0.80 vs. 0.98) and better visual acuity (0.80 vs. 0.63) in contrast to the motor trephine. The stage of the disease does not influence functional outcome after excimer laser PKP. Refractive outcomes of femtosecond laser keratoplasty, however, resemble that of the motor trephine. CONCLUSIONS: In contrast to the undisputed clinical advantages of excimer laser keratoplasty with orientation teeth/notches in keratoconus, the major disadvantage of femtosecond laser application is still the necessity of suction and applanation of the cone during trephination with intraoperative pitfalls and high postoperative astigmatism.

Excimer versus Femtosecond Laser Assisted Penetrating Keratoplasty in Keratoconus and Fuchs Dystrophy: Intraoperative Pitfalls.

Purpose. To assess the intraoperative results comparing two non-mechanical laser assisted penetrating keratoplasty approaches in keratoconus and Fuchs dystrophy. Patients and Methods. 68 patients (age 18 to 87 years) with keratoconus or Fuchs dystrophy were randomly distributed to 4 groups. 35 eyes with keratoconus and 33 eyes with Fuchs dystrophy were treated with either excimer laser ([Exc] groups I and II) or femtosecond laser-assisted ([FLAK] groups III and IV) penetrating keratoplasty. Main intraoperative outcome measures included intraoperative decentration, need for additional interrupted sutures, alignment of orientation markers, and intraocular positive pressure (vis a tergo). Results. Intraoperative recipient decentration occurred in 4 eyes of groups III/IV but in none of groups I/II. Additional interrupted sutures were not necessary in groups I/II but in 5 eyes of groups III/IV. Orientation markers were all aligned in groups I/II but were partly misaligned in 8 eyes of groups III/IV. Intraocular positive pressure grade was recognized in 12 eyes of groups I/II and in 19 eyes of groups III/IV. In particular, in group III, severe vis a tergo occurred in 8 eyes. Conclusions. Intraoperative decentration, misalignment of the donor in the recipient bed, and need for additional interrupted sutures as well as high percentage of severe intraocular positive pressure were predominantly present in the femtosecond laser in keratoconus eyes.

Ocular side effects of biological agents in oncology: what should the clinician be aware of?

During the last 20 years, biologicals have become increasingly relevant in oncologic therapy. Depending on the medication used, there are different profiles of ocular side effects. Although these can be present in up to 70% of patients, they are generally underreported in the literature. Therefore, the pathophysiological details of their development are often poorly understood. Herein we attempt to identify groups of biologicals to which a specific side effect profile can be assigned. We also tried to capture all relevant side effects and therefore conducted several database investigation including Medline, Cochrane library, and the drugs section of the US Food and Drug Administration (FDA), using the following search strings: "name of biological agent (both generic and commercial names)" AND "eye" OR "ocular". If we found a side effect that has been associated with a drug, we researched Medline using the following search string: "name of biological agent" (both generic and commercial names) AND "term for the specific side effect". Due to the wealth of material we report only the drugs that are approved by the FDA.

Low temperature synthesis of monodisperse nanoscaled ZrO2 with a large specific surface area.

Thermal decomposition of Zr(C(2)O(4))(2)·4H(2)O within an autoclave or in a conventional tube furnace at temperatures below 380 °C resulted in nano- and micron-sized ZrO(2), respectively. Reactions under autogenic pressure yielded monodisperse monoclinic (m) and tetragonal (t) ZrO(2) nanoparticles with an average diameter of ~8 nm and interconnected t-ZrO(2) nanoparticles with diameters of ~4 nm, depending on the synthesis temperature. Samples were characterised by X-ray diffraction (XRD), small angle X-ray scattering (SAXS), scanning electron microscopy (SEM), transmission electron microscopy (TEM) associated with energy dispersive X-ray spectroscopy (EDS), Raman microspectroscopy and photoluminescence spectroscopy (PL). Nanostructured zirconia materials exhibited high specific areas of 276-385 m(2) g(-1) which make them promising candidates as catalysts and catalyst supports. Co-existence of m- and t-ZrO(2) nanoparticles with diameters of 6-9 nm, i.e. above the critical particle size of 6 nm for the formation of t-ZrO(2), demonstrated that the particle size is not the only factor for stabilisation of the t-ZrO(2) modification at room temperature.