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Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. Objective: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. Methods and Results: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10 -10 , OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10 -5 ). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A , which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A . Genomic and functional data support a causal role of WNT5A at the locus.

Background: Facing the global COVID-19 pandemic University teaching has been digitalized and German medical faculties took great effort to offer curricular contents online as they agreed that semesters during pandemic should not be suspended. Skill training is an essential part of medical education and cannot be fully digitalized nor should it be omitted. The pandemic demonstrates that skills like ultrasound are essential when treating critical ill patients. Medical faculties use peer assisted learning (PAL) concepts to teach skills, like ultrasound through specially trained student tutors. Aim: Here, we would like to share our experiences and elaborate how ultrasound teaching can be safely performed during the pandemic with an emphasis on adjustment of an existing PAL teaching concept. Method: At the hospital of Saarland University, we implemented a PAL teaching concept for abdominal, including emergency, ultrasound, and echocardiography, called “sonoBYstudents” to teach sonography to undergraduate medical students. Students are generally taught in small groups of 5 people in 90min sessions over a time of 8 weeks with an objective structured clinical exam (OSCE) at the end of the course program. Each semester nearly 50 students are taught in abdominal and emergency ultrasound and 30 students in echocardiography. Over five years, more than 600 students have been taught with at least 30 students being trained as student tutors. Given the pandemic, course size, course interval and total course time and total course time were adapted to the hygienic precautions. Results: 45 and 30 students were taught in abdominal ultrasound and echocardiography respectively achieving their learning goals measured via OSCE at the end of the courses. OSCE results were the same when compared to previous semesters. Conclusion: PAL as a teaching concept lives out of sustained educational strategies like practical and didactical trainings and an ongoing recruitment of new student tutors. Suspending PAL and its skill teaching would require starting from the beginning which is a time and cost consuming process. With sonoBYstudents we were able to demonstrate that an existing PAL concept can, with some effort, be adjusted to changing teaching circumstances. Apart from this ultrasound is a non-omittable part of medical skill training with easily appliable hygienic precautions during teaching sessions., Hintergrund: Die globale COVID-19-Pandemie führte zu einer raschen Digitalisierung der universitären Lehre. Innerhalb der medizinischen Fakultäten Deutschlands herrschte der Konsens, dass während der Pandemie kein Semester ausgesetzt werden soll. Daher wurden mit viel Mühe, weite Teile der Lehrinhalte online angeboten. Das Unterrichten von praktischen Fertigkeiten ist ein wesentlicher Bestandteil der medizinischen Ausbildung und kann nicht digitalisiert, jedoch auch nicht ausgelassen werden. Die Pandemie zeigt, dass praktische Fertigkeiten wie Ultraschall bei der Behandlung kritisch kranker Patienten unerlässlich sind. Die medizinischen Fakultäten in Deutschland nutzen daher Peer-Assisted-Learning (PAL) Konzepte, als modernes Lehrmodel, um solche praktischen Fertigkeiten, wie Ultraschall, durch speziell ausgebildete studentische Tutoren zu vermitteln. Ziel: Wir möchten unsere Erfahrung teilen und aufzeigen, wie der studentische Ultraschallunterricht während der Pandemie sicher durchgeführt werden kann, wobei der Schwerpunkt auf der Anpassung eines bestehenden PAL-Lehrkonzepts liegt. Methode: An der medizinischen Fakultät der Universität des Saarlandes, führten wir vor 5 Jahren ein PAL-Lehrkonzept, genannt „sonoBYstudents“, ein um Medizinstudenten in der Abdomen-, einschließlich Notfall-Sonographie und Echokardiographie zu unterrichten. Die Studenten werden in Kleingruppen à 5 Personen in 90-minütigen praktischen Seminaren über einen Zeitraum von 8 Wochen unterrichtet. Der Lernerfolg wird durch eine validierte OSCE (objective structured clinical examination) am Ende des Kursprogramms überprüft. Jedes Semester werden ca. 60 Studenten in der Abdomen- und Notfall-Sonographie und 30 Studenten in der Echokardiographie unterrichtet. In fünf Jahren konnten mehr als 600 Studenten unterrichtet sowie mehr als 30 Studenten als studentische Tutoren ausgebildet. Aktuell wurden angesichts der Pandemie Kursgröße, Kursintervall und Gesamtkurszeit, entsprechend einem Hygienekonzept, angepasst. Ergebnisse: 45 bzw. 30 Studenten wurden in der Abdomensonographie und in der Echokardiographie unterrichtet und erreichten am Ende der Kurse ihre über die OSCE gemessenen Lernziele. Die Ergebnisse der OSCE zeigten keinen signifikanten Unterschied im Vergleich zu den Vor-Semestern. Schlussfolgerung: PAL als Lehrkonzept lebt von nachhaltigen Ausbildungsstrategien wie praktischen und didaktischen Schulungen und einer kontinuierlichen Rekrutierung neuer studentischer Tutoren. Das Pausieren eines bestehenden PAL-Konzeptes und seiner Kompetenzvermittlung würde eine beinahe neue Implementierung nach Pausierung erfordern, was ein zeit- und kostenaufwändiger Prozess ist. Mit sonoBYstudents konnten wir zeigen, dass ein bestehendes PAL-Konzept mit etwas Aufwand an sich ändernde Unterrichtsbedingungen angepasst werden kann, ohne den Lernerfolg der Veranstaltung zu mindern. Letztlich ist die Sonographie unverzichtbarer Teil der medizinischen Ausbildung und eine wichtige medizinische Fertigkeit. Wir konnten zeigen, dass die Ultraschallausbildung im Medizinstudium mit für jeden leicht anwendbaren und nachvollziehbaren hygienischen Vorkehrungen während des Kleingruppenunterrichts fortgeführt werden kann., GMS Journal for Medical Education; 38(1):Doc5

Purpose To describe the outcomes of allograft ocular surface stem cell transplantation (OSST) and the complication profile of systemic immunosuppression (SI) in pediatric patients with limbal stem cell deficiency. Methods This was a retrospective interventional case series from a single tertiary referral institution of 20 eyes from 13 patients who 1) underwent allograft OSST surgery, 2) were 18 years or less at time of OSST, and 3) received SI with 4) a minimum of 12-months follow-up. The main outcome measures were ocular surface stability, visual acuity, and SI adverse events. Results The mean age of patients was 15.1 ± 3.2 years (range 9-18 years). The mean follow-up was 5.6 ± 5.0 years after OSST. At the last follow-up, 15 eyes (75%) had a stable ocular surface, 1 eye (5%) developed partial failure, and 4 eyes (20%) developed total surface failure. Preoperative mean logarithm of the minimum angle of resolution visual acuity 1.5 improved to 1.1 at the last follow-up (P = 0.1); when 4 eyes of 3 nonadherent patients were excluded, the results were more pronounced and statistically significant (1.5 improved to 1.0, P = 0.002). SI was tolerated well by all patients with minimal adverse events. Conclusions OSST provides a stable ocular surface and is a successful treatment option for pediatric patients with limbal stem cell deficiency. SI is well-tolerated with a minimal complication profile.

Objective To describe a new/modified technique to manage posterior vitreous pressure (PVP) during penetrating keratoplasty (PKP) and report a small series. Design Retrospective interventional case series and technique description. Participants PKP eyes necessitating mattress suture placement owing to PVP. Methods Retrospective chart review from 2016 to 2019 was undertaken. Placed prophylactically (before trephination) or after trephination, the mattress suture is placed limbus-to-limbus across the anterior chamber. A second mattress suture can be placed in the opposite meridian (perpendicularly) for added support (safety basket configuration). Variations of suture technique are described based on lens status (i.e., phakic, pseudophakic, aphakic) and intraoperative timing. Parameters assessed included demographics, lens status, suture indications, intraoperative technique details, successful PKP completion, and presence of primary failure. Results There were 6 phakic eyes (5 patients) and 9 pseudophakic/aphakic eyes (8 patients). Indications for the phakic subgroup were obesity (83%), poor scleral rigidity (83%), repeated iris prolapse (67%), dense mature cataract (33%), and planned large-diameter PKP (33%). Indications for pseudophakic/aphakic eyes included intraocular lens/iris prolapse (100%), pre-existing iris defects (67%), and planned large-diameter PKP (33%). Successful PKP was performed in all cases. Whereas one case had residual corneal edema in the setting of a persistent epithelial defect owing to limbal stem cell deficiency, all other cases demonstrated no primary graft failure. Conclusions Although increased PVP can present a stressful and challenging situation, it is important to have multiple options for management. This simple mattress suture technique normalizes the lens-iris complex behaviour and appears safe for the donor graft.

Purpose To compare the long-term outcomes of living-related conjunctival limbal allograft (lr-CLAL) with keratolimbal allograft (KLAL) in patients with limbal stem cell deficiency. Methods A retrospective, comparative, interventional cohort of patients with bilateral total limbal stem cell deficiency who underwent surgical treatment with a KLAL or lr-CLAL procedure alone (not combined with any other ocular surface stem cell transplantation procedures) with a minimum follow-up of 1 year and who received systemic immunosuppression. Ocular surface stability, best-corrected visual acuity (BCVA), and postoperative complications at the last follow-up were the main outcome measures. Results There were 224 eyes that underwent KLAL alone and 63 eyes that underwent lr-CLAL alone, with a mean follow-up time for all eyes of 7.2 years (range 1.0-16.0 years). For lr-CLAL eyes, 82.5% maintained a stable ocular surface compared with 64.7% of KLAL eyes at the last follow-up. Only 6.3% of lr-CLAL eyes demonstrated a failed ocular surface compared with 15.6% of KLAL eyes. The mean BCVA was 20/158 for KLAL eyes compared with 20/100 for lr-CLAL eyes at the last follow-up. A smaller proportion of lr-CLAL eyes (30.2% compared with 43.3%) developed an episode of acute rejection, and a higher proportion of these episodes resolved with treatment in the lr-CLAL group (79.0% compared with 53.6%). Conclusions lr-CLAL demonstrates lower rejection rates, improved graft survival, and better BCVA compared with KLAL. Both careful preoperative donor selection and triple-agent systemic immunosuppression (including tapered systemic corticosteroids) are critical to optimizing the ocular surface stem cell transplantation outcomes.

Objective To study indications for penetrating keratoplasty (PK) at a single site. The trends in the causative organisms for infectious keratitis requiring surgery were also evaluated. Design Retrospective observational study. Participants A total of 1181 eyes of 935 patients undergoing PK between January 2000 and December 2015 in Northern Alberta, Canada. Methods Indications for PK were evaluated over the 16-year study period, and the trends in these indications were compared over 5-year intervals. The microbiology of infectious keratitis cases requiring surgery was similarly evaluated. Results The most common indications for PK from 2000 to 2015 were keratoconus (23%), re-graft (22%), and corneal scar (12%). There was a decline in the percent of total surgeries done for Fuchs’ dystrophy (p = 1.1 × 10−3) and pseudophakic bullous keratopathy (p = 5.6 × 10−5), whereas a corresponding increase in keratoconus (p = 3.2 × 10−5), trauma (p = 2.1 × 10−3), and infectious keratitis cases (p = 0.010) was observed. The most common causes for infectious keratitis cases were viral (45%), bacterial (18%), parasitic (11%), and fungal (9%). There was a significant increase in the percent of infectious keratitis cases due to a viral etiology from 2005 to 2010 (p = 6.4 × 10−3). Conclusions The indications for PK are comparable with other centres in North America. Nearly half of all infectious keratitis cases requiring surgery are viral. The increase in viral cases requiring surgery may reflect improved diagnostics or recurrent cases.

To describe the rate, clinical/microbiological characteristics, and outcomes of infectious keratitis in eyes with limbal stem cell deficiency after ocular surface stem cell transplantation (OSST).In this retrospective chart review of 278 eyes that underwent OSST between January 2006 and December 2016, eyes treated for previous infectious keratitis (bacterial, fungal, or viral) were included. Demographics, risk factors, course, microbiological characteristics, and outcomes were assessed.A total of 52 eyes (18.7%) of 48 patients (28 men and 20 women) developed 75 episodes (culture-proven or presumed) of infectious keratitis (range 1-4 episodes) with mean follow-up of 5.3 ± 3.6 years after OSST. The most common limbal stem cell deficiency etiologies included chemical/thermal (27 episodes), Stevens-Johnson syndrome (19 episodes), aniridia (8 episodes), and mucous membrane pemphigoid (8 episodes). There were 44 (58.7%) bacterial keratitis episodes, 24 (32%) fungal keratitis episodes, and 7 (9.3%) HSV keratitis episodes. Gram-positive bacteria (79%) and Candida species (73%) were the most common bacterial and fungal pathogens. Before infection, 33% had an epithelial defect, 69% had a bandage contact lens, 91% were on systemic immunosuppression, and 25% recently had undergone ocular surgery (3 months). Although 75% resolved with antimicrobial treatment, 25% required a therapeutic keratoplasty (TPK; 2 cases needed multiple TPK).Despite successful OSST surgery, infectious keratitis is relatively common, and aggressive medical/surgical therapy is warranted. Prophylactic topical antibiotics and a cicatrizing conjunctivitis diagnosis may account for the high proportion of fungal keratitis in this population.

PURPOSE To report a case of extensive Fuchs superficial marginal keratitis managed with annular lamellar keratoplasty. METHODS Interventional case report. RESULTS A 72-year-old man presented with 20/80 best-corrected visual acuity in his left eye and demonstrated 360-degree peripheral deep immune stromal keratitis and pseudopterygia with peripheral stromal thinning. During superficial keratectomy with amniotic membrane transplantation, the thin cornea was perforated while excising pseudopterygia in the superonasal quadrant. Surgery was aborted. Anterior segment optical coherence tomography demonstrated a severely thinned cornea (240 μm nasally, 360 μm temporally) with overlying pseudopterygia peripherally. After allowing 3 months for the cornea to heal, the decision was made to perform lamellar annular (or "donut") keratoplasty. The patient had an unremarkable postoperative course, with 20/50 best-corrected visual acuity 10 months after keratoplasty. CONCLUSIONS We report an extensive case of Fuchs superficial marginal keratitis treated with 360-degree annular lamellar keratoplasty. This technique provides tectonic support to decrease the likelihood of future perforation while also improving vision by modifying the ectatic cornea. Anterior segment optical coherence tomography may be a helpful tool preoperatively to avoid severely thinned areas (eg, during pseduopterygium removal) and to ensure complete removal of the ectatic cornea.

Purpose To report our surgical experience with ocular surface stem cell transplantation (OSST) for limbal stem cell deficiency (LSCD) in the setting of keratitis-ichthyosis-deafness (KID) syndrome. Methods Retrospective interventional case series. Results We present 5 eyes of 3 patients with KID syndrome that developed LSCD and underwent OSST. Mean follow-up after OSST was 8.3 ± 4.3 years (range 3.4-11.4 years). Two eyes underwent living-related conjunctival limbal allograft (lr-CLAL), and 3 eyes were treated with keratolimbal allograft (KLAL). Four of the 5 eyes underwent subsequent keratoplasty. Both lr-CLAL eyes maintained a stable ocular surface at final follow-up. Conversely, all KLAL eyes developed a failed surface requiring repeat KLAL surgery. Because of multiple failed KLALs, 1 eye underwent placement of a keratoprosthesis. Conclusions KID syndrome is a rare cause of LSCD. Although OSST can stabilize the surface, long-term treatment of KID syndrome can be challenging. An lr-CLAL may offer further benefit over a KLAL in these eyes because it is HLA- and ABO-matched tissue; it also helps to treat keratoconjunctivitis sicca, often a prominent feature of KID syndrome.

To investigate the long-term clinical outcomes of conjunctival limbal autograft (CLAU) in patients with unilateral total limbal stem cell deficiency (LSCD).In this retrospective interventional case series, the medical charts of patients with unilateral total LSCD were reviewed. Patients who underwent CLAU and no other allograft ocular stem cell transplantation with a minimum follow-up of 1 year were included. Main outcome measures were ocular surface stability, best-corrected visual acuity (BCVA), and postoperative complications.27 eyes fulfilled the inclusion criteria with a mean follow-up period of 49.8 ± 36.6 months (4.15 years; range 12-186.72 months; 1-15.56 years). Ocular surface stability was achieved in 77.8% (n = 21) of eyes at last follow-up, while 22.2% (n = 6) developed partial surface failure. Optical penetrating or deep lamellar anterior keratoplasty was performed in 44.45% (n = 12). BCVA improved from 1.42 ± 0.95 mean LogMAR (equivalent to 20/400) preoperatively to 0.53 ± 0.47 mean LogMAR (equivalent to 20/70) at last follow-up (p 0.001). BCVA ≥20/40 was achieved in 44.45% (n = 12) at last follow-up. Microbial keratitis occurred in 14.81% (n = 4). Ocular hypertension secondary to corticosteroid use developed in 25.9% (7/27) eyes. There were no other complications in the donor or recipient eyes.CLAU can provide long-term ocular surface stability and successful visual outcomes in patients with unilateral LSCD.

Purpose To compare the visual outcomes and complications between nanothin Descemet stripping automated endothelial keratoplasty (NT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). Methods A prospective comparative case series of 28 consecutive cases of NT-DSAEK (less than or equal to 50 μm) and DMEK was undertaken. Inclusion criteria were a diagnosis of Fuchs dystrophy, presence of pseudophakia, or planned combined cataract surgery/endothelial keratoplasty, with a minimum of 6-month follow-up. Exclusion criteria were any concurrent ocular comorbidities. Primary outcomes measures were best spectacle-corrected visual acuity (BSCVA) and complications. Results Mean thickness of NT-DSAEK grafts was 41.0 ± 7.5 μm (range 26-50 μm). At 1 month postoperatively, the DMEK group had significantly better mean BSCVA of 0.18 ± 0.20 logarithm of the minimum angle of resolution (logMAR) (20/33) compared with 0.28 ± 0.16 logMAR (20/40) for NT-NSAEK (P = 0.049). At 3, 6, and 12 months postoperatively, mean BSCVA was comparable between both groups [3 months: NT-DSAEK 0.17 ± 0.12 logMAR (20/30) versus DMEK 0.13 ± 0.17 (20/27), P = 0.31; 6 months: NT-DSAEK 0.11 ± 0.10 logMAR (20/26) versus DMEK 0.09 ± 0.10 (20/25), P = 0.63; 12 months: NT-DSAEK 0.07 ± 0.09 logMAR (20/24) versus DMEK 0.07 ± 0.11 logMAR (20/24), P = 0.95]. Other than 1 NT-DSAEK graft that was successfully rebubbled, no other complications were encountered in either group. Conclusions Compared with DMEK, NT-DSAEK provides comparable visual outcomes and complications rates.

Aim & objective Severe ocular surface disease, including limbal stem cell deficiency (LSCD) can occur as a consequence of severe atopic keratoconjunctivitis (AKC) that has been inadequately treated. Our goal was to describe the management and outcomes of severe ocular surface disease in AKC patients. Methods We performed a retrospective analysis of a case series of 13 eyes of 8 patients with advanced ocular surface disease associated with severe AKC. The clinical presentation, medical and surgical management, and visual and anatomic outcomes were analyzed. Results Five eyes were treated with medical interventions alone, which included topical or systemic immunomodulatory therapy (IMT) for all eyes. These eyes had a decline in mean visual acuity from LogMAR 0.96 to 2.04 between the initial and final visits related to recurrent epithelial defects or corneal ulceration. Eight eyes were treated with surgical approaches in addition to medical treatment. Initial surgical treatments included limbal stem cell transplantation (n = 5), Boston keratoprosthesis (n = 2), and superficial keratectomy (n = 1). Both eyes that underwent primary keratoprosthesis had severe post-operative complications and became no light perception. In the remainder of the surgically treated eyes, there was an improvement visual acuity from LogMAR 1.43 to 0.6 between the pre-operative and final post-operative visit. Conclusion Visual rehabilitation in eyes severe ocular surface disease due to prolonged AKC is challenging. While some patients did experience improved vision, most eyes did not improve or experienced severe complications with vision loss. Early intervention with immunomodulatory therapy may prevent progression of the disease to advanced stages.

PURPOSE To describe our process for preoperative screening and donor selection for ocular surface stem cell transplantation (OSST). METHODS A 7-year retrospective chart review was performed on limbal stem cell deficiency patients. The inclusion criterion was all patients who underwent an OSST procedure. The exclusion criterion was eyes with unilateral disease in which an autograft was performed. Data for human leukocyte antigen (HLA) typing, virtual crossmatching, donor-specific antibody, and panel reactive antibody level were obtained. RESULTS Of the included 142 eyes (104 patients), 19 patients had no recorded living donor availability data, and HLA typing was not performed on 16 patients. A total of 94 donors (mean 1.4 donors/patient, range 1-6) were tested for 67 recipients. For 2 patients with graft-versus-host disease, no further HLA typing was needed, as the donors were known HLA-identical donors. For 47 patients, only 1 donor was tested, whereas multiple donors underwent HLA typing for 20 patients. There were 73 ABO (blood group)-compatible matches for the 61 tested recipients, and only 1 recipient did not have any ABO-compatible donor. For the virtual crossmatch, there were 5 patients who did not have a compatible donor (positive virtual crossmatch). The best available donor match was a sibling for 41 recipients (65%), a parent for 19 recipients (30%), and an offspring for 3 recipients (5%). CONCLUSIONS Our protocol for OSST preoperative screening and donor selection minimizes the antigenic burden for transplanted tissue by selecting the best available donor match.

The cornea is unique because of its complete avascularity. Corneal neovascularization (CNV) can result from a variety of etiologies including contact lens wear; corneal infections; and ocular surface diseases due to inflammation, chemical injury, and limbal stem cell deficiency. Management is focused primarily on the etiology and pathophysiology causing the CNV and involves medical and surgical options. Because inflammation is a key factor in the pathophysiology of CNV, corticosteroids and other anti-inflammatory medications remain the mainstay of treatment. Anti-VEGF therapies are gaining popularity to prevent CNV in a number of etiologies. Surgical options including vessel occlusion and ocular surface reconstruction are other options depending on etiology and response to medical therapy. Future therapies should provide more effective treatment options for the management of CNV.

Objective To investigate efficacy and safety of phaco-trabectome (PT) versus phaco-iStent (Pi) for intraocular pressure (IOP) control in open-angle glaucoma (OAG). Design Retrospective comparative case series. Participants A total of 70 eyes of 55 patients with OAG underwent either PT surgery by a single surgeon or Pi (insertion of 2 stents) by another surgeon in Canada between January 2010 and December 2012. Methods The medical records of consecutive adult patients who underwent either PT or Pi surgery were reviewed. All patients who satisfied both the inclusion and exclusion criteria were included in the outcomes analyses. IOP reduction, reduction in glaucoma medication, safety profile, and best-corrected visual acuity were evaluated. Results Thirty-six eyes of 30 patients had PT and 34 eyes of 25 patients had Pi. Baseline IOP was higher in the PT group (20.92 ± 5.07 mm Hg) than in the Pi group (17.47 ± 4.87 mm Hg; p = 0.026). At 12 months there was no significant difference between groups in relative reduction of mean IOP (PT −5.09 ± 5.73, 24% relative reduction vs. Pi −3.84 ± 3.80, 22% relative reduction; p = 0.331) or glaucoma medication use (PT −0.49 ± 1.17 vs. Pi −0.26 ± 0.73; p = 0.168) from baseline. However, Pi had significantly fewer individual complications (PT 20 vs. Pi 5; p Conclusion At 12 months of follow-up, both techniques significantly lowered IOP, but fewer complications were observed in the Pi group.

Based on the authors' experience with reconstruction of the heart using three-dimensional echocardiography, the authors assessed the feasibility of three-dimensional reconstruction of brain images using transfontanelle ultrasound in selected cases of infants with abnormal intracranial findings. A conventional 5-MHz ultrasound transducer inside a transducer holder was rotated 180 degrees around its vertical axis using a computer-controlled stepper motor to acquire multiple sequential cross-sections of the brain. The raw digital data of this three-dimensionally recorded dataset were transferred to a PC-based workstation for further analysis. The reconstruction of the three-dimensional brain images and volumetric analysis were undertaken using a new dedicated software capable of three-dimensional reconstruction and volumetric analysis (Echo-PAC-3D, version 1.2 Beta, GE Vingmed, Horton, Norway). The reconstruction of sequential slices from the stored three-dimensional data allowed the visualization of the epicortical extension and volumetric measurements of the focal ischemic infarction in the superior tempoparietal lobe in a 2-week-old newborn with a focal ischemic brain lesion. In other 2-week-old newborns, the extension and volume of a periventricular hemorrhage was visualized by three-dimensional reconstruction of coronal cross-sectional images from the acquired three-dimensional dataset. The three-dimensional reconstruction of the lateral ventricles allowed the three-dimensional visualization and estimation of ventricular dilatation in milliliters in an 8-week-old infant with hydrocephalus. Three-dimensional reconstruction of brain images and volume estimation of brain lesions and cavities by ultrasound may provide new insights into the morphology and extension of ultrasonographically visible brain lesions.

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly. The disease is characterized by extracellular deposits known as drusen, which are found between the basal lamina of the retinal pigment epithelium (RPE) and the inner layer of Bruch’s membrane (BM). Although, the presence of drusen correlates with the development of AMD, the specific mechanisms underlying the biogenesis of drusen and its relationship to the disease remain elusive.1–3 Extensive biochemical analysis of drusen revealed the presence of several proteins linked to inflammation. Such proteins include immunoglobulins, acute-phase molecules (vitronectin, amyloid P, and fibrinogen), complement factors (C5 and C5b-9), and complement regulatory molecules (clusterin and complement receptor 1).4–8 These findings implicate an inflammatory process associated with drusen, but what activates or triggers the inflammation remains unknown.4,9–12 Several lines of evidence suggest that amyloid-β1-40 (Aβ1-40), a known constituent of drusen, is a potential candidate trigger peptide.3,13–15 Genetically modified mice with increased Aβ deposition display many traits consistent with human AMD, such as the accumulation of sub-RPE deposits, microglial activation, and degeneration of the retinal neurons and RPE.16,17 In the retina, cell types including neurons, RPE, and glia may provide a local source of Aβ species; they have been shown to have the cellular machinery for the synthesis of amyloid precursor protein (APP) and cleavage enzymes.10 Sequential APP processing by β- and γ-secretase produces the major Aβ species, Aβ1-40. Recent in vitro studies in which RPE cells are stimulated with Aβ1-40 demonstrated several results that are consistent with a proinflammatory response. Wang et al.18 reported that Aβ1-40 stimulation caused abnormal activity of complement factor I (CFI), an inhibitory regulator of the complement cascade. In another study, stimulation of RPE cells with Aβ1-40 modulated the expression of vascular endothelial growth factor (VEGF), which is known to promote angiogenesis, a late-stage feature of AMD.17 These results prompted us to further elucidate the effects of Aβ1-40 stimulation on RPE cells in vitro by differential microarrays and corresponding functional pathway analysis. We hypothesize that Aβ1-40 stimulation of RPE cells in vitro promotes gene expression changes associated with cellular pathways implicated in the pathogenesis of AMD, including oxidative stress, inflammation, angiogenesis, and apoptosis.