Bilateral fingolimod-associated macular oedema development after cataract surgery.

Postoperative cystoid macular oedema (CMO) is a recognised complication of cataract surgery, occurring in around 1.5% of cases. It is generally managed with topical steroids or non-steroidal anti-inflammatory medications. We present a case of a patient who developed bilateral sequential CMO following bilateral sequential cataract surgery which was non-responsive to topical therapy and worsened following sub-Tenons administration of steroid. The patient took fingolimod for multiple sclerosis both prior to and during the period of cataract surgery which is known to result in the development of macular oedema in some patients. On fingolimod cessation, the oedema resolved over a period of 5 months with good visual recovery. We present this case to inform cataract surgeons of the risk of fingolimod-associated macular oedema in patients undergoing cataract surgery and to inform neurologists of the potential need to adjust treatment for patients undergoing cataract surgery.

Intravitreal aflibercept (A-IVI) for the treatment of neovascular age-related macular degeneration (nv-AMD): one year experience.

OBJECTIVE: To report the anatomical and functional results of intravitreal injections of aflibercept (Eylea) (A-IVI) for the treatment of naïve eyes with neovascular age-related macular degeneration (nv-AMD). SUBJECTS AND METHODS: This retrospective, one-center, non-comparative chart review included 26 treatment naïve eyes with nv-AMD of 26 patients (14 male) with a mean age of 80.5 (range 63-91) who had a complete follow-up of 14 months. The morphological analysis included spectral domain optical coherence tomography and fundus fluorescein angiography, while the functional assessment included logarithm of the minimum angle of resolution (LogMAR) best correct visual acuity (BCVA). The timing of the follow-up was: baseline, 3, 6, and 14 months. All patients received 8 A-IVI according to the protocol (first 3 consecutive monthly A-IVI, followed by bi-monthly retreatment for the first year, regardless of disease activity as per local guidelines). Statistical analysis was performed using ANOVA. Improvement of visual acuity more than 15 letters was considered as "improvement", less than 5 letters as "stable" and any letter loss as "worsening". RESULTS: Mean±standard deviation LogMAR visual acuity improved from 0.26±0.15 at presentation to 0.14±0.20 at the final follow-up of 14 months (P=0.02). BCVA was stable in 23.1%, improved in 61.5% (16 eyes) worsened in 15.4%. A mean pretreatment central macular thickness of 409µm reduced significantly to 229µm at month 14 (P<0.02). The OCT of eyes with worsened BCVA showed resolution of retinal fluid but presence of subretinal fibrosis. No adverse events were attributed to aflibercept. CONCLUSIONS: Patients who had a worsening in visual acuity were found to have longer duration of symptoms prior to treatment and presence of geographic atrophy, and/or subretinal haemorrhage and/or subretinal fibrosis at baseline. From our experience, with 14 months follow-up, A-IVI is an effective treatment for treatment naïve patients with nv-AMD. Our real world results were similar to pivotal trials.

Hypoxia-inducible factors regulate filaggrin expression and epidermal barrier function.

A functional epidermal skin barrier requires the formation of a cornified envelope from terminally differentiating keratinocytes. During this process, multiple genetic and environmental signals coordinately regulate protein expression and tissue differentiation. Here we describe a critical role for hypoxia-inducible factors (HIFs) in the regulation of filaggrin expression and skin barrier formation. Similar to other mammalian tissues, fetal epidermis in mice is normally O2 deprived. Simultaneous deletion of Hif1a and Hif2a in murine epidermis revealed defects in keratinocyte terminal differentiation and epidermal barrier formation. Mice lacking Hif1a and Hif2a in the epidermis exhibited dry flaky skin, impaired permeability barrier, and enhanced sensitivity to cutaneous allergens. These defects were correlated with stratum granulosum attenuation and reduced filaggrin expression. Hypoxic treatment of primary keratinocytes induced filaggrin (Flg) gene expression in a HIF1α- and HIF2α-dependent manner, suggesting that one mechanism by which Hif1a and Hif2a loss causes epidermal barrier defects in mice lies in Flg dysregulation. Therefore, low O2 tension is an essential component of the epidermal environment that contributes to skin development and function.

Early features in acute macular neuroretinopathy.

Acute macular neuroretinopathy (AMNR) is a rare disorder characterised by acute onset of unilateral or bilateral visual impairment associated with reddish-brown wedge-shaped outer macular lesions. It is more frequently reported in young females and though the pathophysiology remains unclear, factors reported in association with its onset include post-viral illness and vasoconstrictor use. We report a case of AMNR in an 18-year old female patient presenting with a 2-day history of acute painless blurring of central vision bilaterally, following 1 month of preceding flu-like illness. For 1 week prior to presentation, the patient had taken large doses of oral preparations containing phenylephrine hydrochloride. In addition to demonstrating characteristic optical coherence tomography findings seen in AMNR, we illustrate some rarely seen acute ophthalmoscopic features. Based on associations from this case, we add further insight into the pathophysiology of this condition which remains poorly understood.

Effect of gold marker seeds on magnetic resonance spectroscopy of the prostate.

PURPOSE: Magnetic resonance stereoscopic imaging (MRSI) of the prostate is an emerging technique that may enhance targeting and assessment in radiotherapy. Current practices in radiotherapy invariably involve image guidance. Gold seed fiducial markers are often used to perform daily prostate localization. If MRSI is to be used in targeting prostate cancer and therapy assessment, the impact of gold seeds on MRSI must be investigated. The purpose of this study was to quantify the effects of gold seeds on the quality of MRSI data acquired in phantom experiments. METHODS AND MATERIALS: A cylindrical plastic phantom with a spherical cavity 10 centimeters in diameter wss filled with water solution containing choline, creatine, and citrate. A gold seed fiducial marker was put near the center of the phantom mounted on a plastic stem. Spectra were acquired at 1.5 Tesla by use of a clinical MRSI sequence. The ratios of choline + creatine to citrate (CC/Ci) were compared in the presence and absence of gold seeds. Spectra in the vicinity of the gold seed were analyzed. RESULTS: The maximum coefficient of variation of CC/Ci induced by the gold seed was found to be 10% in phantom experiments at 1.5 T. CONCLUSION: MRSI can be used in prostate radiotherapy in the presence of gold seed markers. Gold seeds cause small effects (in the order of the standard deviation) on the ratio of the metabolite's CC/Ci in the phantom study done on a 1.5-T scanner. It is expected that gold seed markers will have similar negligible effect on spectra from prostate patients. The maximum of 10% of variation in CC/Ci found in the phantom study also sets a limit on the threshold accuracy of CC/Ci values for deciding whether the tissue characterized by a local spectrum is considered malignant and whether it is a candidate for local boost in radiotherapy dose.

The von Hippel-Lindau Chuvash mutation promotes pulmonary hypertension and fibrosis in mice.

Mutation of the von Hippel-Lindau (VHL) tumor suppressor protein at codon 200 (R200W) is associated with a disease known as Chuvash polycythemia. In addition to polycythemia, Chuvash patients have pulmonary hypertension and increased respiratory rates, although the pathophysiological basis of these symptoms is unclear. Here we sought to address this issue by studying mice homozygous for the R200W Vhl mutation (VhlR/R mice) as a model for Chuvash disease. These mice developed pulmonary hypertension independently of polycythemia and enhanced normoxic respiration similar to Chuvash patients, further validating VhlR/R mice as a model for Chuvash disease. Lungs from VhlR/R mice exhibited pulmonary vascular remodeling, hemorrhage, edema, and macrophage infiltration, and lungs from older mice also exhibited fibrosis. HIF-2alpha activity was increased in lungs from VhlR/R mice, and heterozygosity for Hif2a, but not Hif1a, genetically suppressed both the polycythemia and pulmonary hypertension in the VhlR/R mice. Furthermore, Hif2a heterozygosity resulted in partial protection against vascular remodeling, hemorrhage, and edema, but not inflammation, in VhlR/R lungs, suggesting a selective role for HIF-2alpha in the pulmonary pathology and thereby providing insight into the mechanisms underlying pulmonary hypertension. These findings strongly support a dependency of the Chuvash phenotype on HIF-2alpha and suggest potential treatments for Chuvash patients.

Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice.

To determine the role of surfactant protein C (SP-C) in host defense, SP-C-deficient (Sftpc-/-) mice were infected with the pulmonary pathogen Pseudomonas aeruginosa by intratracheal injection. Survival of young, postnatal day 14 Sftpc-/- mice was decreased in comparison to Sftpc+/+ mice. The sensitivity to Pseudomonas bacteria was specific to the 129S6 strain of Sftpc-/- mice, a strain that spontaneously develops interstitial lung disease-like lung pathology with age. Pulmonary bacterial load and leukocyte infiltration were increased in the lungs of Sftpc-/- mice 24 h after infection. Early influx of polymorphonuclear leukocytes in the lungs of uninfected newborn Sftpc-/- mice relative to Sftpc+/+ mice indicate that the lack of SP-C promotes proinflammatory responses in the lung. Mucin expression, as indicated by Alcian blue staining, was increased in the airways of Sftpc-/- mice following infection. Phagocytic activity of alveolar macrophages from Sftpc-/- mice was reduced. The uptake of fluorescent beads in vitro and the number of bacteria phagocytosed by alveolar macrophages in vivo was decreased in the Sftpc-/- mice. Alveolar macrophages from Sftpc-/- mice expressed markers of alternative activation that are associated with diminished pathogen response and advancing pulmonary fibrosis. These findings implicate SP-C as a modifier of alveolar homeostasis. SP-C plays an important role in innate host defense of the lung, enhancing macrophage-mediated Pseudomonas phagocytosis, clearance and limiting pulmonary inflammatory responses.

Altered postnatal lung development in C3H/HeJ mice.

C3H/HeJ mice develop an increase in terminal air space area detectable by postnatal d 14 that persists into adulthood compared with strain-matched controls (C3H/SnJ, C3H/OuJ). Morphometric quantification revealed a 50% increase in terminal air space area by postnatal d 14 and a 2.3-fold increase by 2 mo of age in C3H/HeJ mice. Bacteriologic cultures obtained from the left lung on postnatal d 7 revealed > 100 colony-forming units (CFU)/left lung of predominantly Gram-negative bacteria (GNB) (Escherichia coli and Proteus mirabilis) in 13 of the 14 C3H/HeJ mice compared with 0 of 12 controls demonstrating colonization of the developing lung in C3H/HeJ mice. An approximately threefold increase in macrophages from bronchoalveolar lavage, threefold increases in matrix metalloproteinase 12 (MMP-12) mRNA and protein levels and elevated levels of proinflammatory cytokines monocyte chemoattractant protein (MCP-1) and keratinocyte-derived cytokine (KC) were also found. P. mirabilis obtained from lung cultures in C3H/HeJ mice induced nuclear factor-kappaB (NF-kappaB) activation in human embryonic kidney 293 (HEK 293) cells transfected with TLR5. In C3H/HeJ mice lacking TLR4 signaling, bacterial colonization is associated with chronic inflammation and permanent changes in lung morphology.

Removal of a capsular tension ring from the anterior chamber angle.

A 75-year-old woman presented with unexplained ocular hypertension 4 weeks after phacoemulsification. Steroid response was diagnosed initially until a misplaced capsular tension ring (CTR) was identified in the drainage angle. We describe the technique used to successfully remove the CTR from the drainage angle with minimal trauma. This case illustrates the importance of the initial surgical technique used for CTR insertion and emphasizes the role of gonioscopy in such a case.

Characteristics and quality assurance of a dedicated open 0.23 T MRI for radiation therapy simulation.

A commercially available open MRI unit is under routine use for radiation therapy simulation. The effects of a gradient distortion correction (GDC) program used to post process the images were assessed by comparison with the known geometry of a phantom. The GDC reduced the magnitude of the distortions at the periphery of the axial images from 12 mm to 2 mm horizontally along the central axis and distortions exceeding 20 mm were reduced to as little as 2 mm at the image periphery. Coronal and sagittal scans produced similar results. Coalescing these data into distortion as a function of radial distance, we found that for radial distances of <10 cm, the distortion after GDC was <2 mm and for radial distances up to 20 cm, the distortion was <5 mm. The dosimetric errors resulting from homogeneous dose calculations with this level of distortion of the external contour is <2%. A set of triangulation lasers has been added to establish a virtual isocenter for convenient setup and marking of patients and phantoms. Repeated measurements of geometric phantoms over several months showed variations in position between the virtual isocenter and the magnetic isocenter were constrained to <2 mm. Additionally, the interscan variations of 12 randomly selected points in space defined by a rectangular grid phantom was found to be within the intraobserver error of approximately 1 mm in the coronal, sagittal, and transverse planes. Thus, the open MRI has sufficient geometric accuracy for most radiation therapy planning and is temporally stable.

Measurement of intrafractional prostate motion using magnetic resonance imaging.

PURPOSE: To quantify the three-dimensional intrafractional prostate motion over typical treatment time intervals with cine-magnetic resonance imaging (cine MRI) studies. METHODS AND MATERIALS: Forty-two patients with prostate cancer were scanned supine in an alpha cradle cast using cine MRI. Twenty sequential slices were acquired in the sagittal and axial planes through the center of the prostate. Each scan took approximately 9 min. The posterior, lateral, and superior edges of the prostate were tracked on each frame relative to the initial prostate position, and the size and duration of each displacement was recorded. RESULTS: The prostate displacements were (mean +/- SD): 0.2 +/- 2.9 mm, 0.0 +/- 3.4 mm, and 0.0 +/- 1.5 mm in the anterior-posterior, superior-inferior, and medial-lateral dimensions respectively. The prostate motion appeared to have been driven by peristalsis in the rectum. Large displacements of the prostate (up to 1.2 cm) moved the prostate both anteriorly and superiorly and in some cases compressed the organ. For such motions, the prostate did not stay displaced, but moved back to its original position. To account for the dosimetric consequences of the motion, we also calculated the time-averaged displacement to be approximately 1 mm. CONCLUSIONS: Cine MRI can be used to measure intrafractional prostate motion. Although intrafractional prostate motions occur, their effects are negligible compared to interfractional motion and setup error. No adjustment in margin is necessary for three-dimensional conformal or intensity-modulated radiation therapy.