FINGERPRINT SIGN OF THE HENLE FIBER LAYER.

PURPOSE: To describe the appearance of concentric, fingerprint-like waves within the Henle fiber layer (HFL) using en face optical coherence tomography in patients with tractional pathologies of the retina. METHODS: Retrospective analysis of six eyes of six patients imaged by optical coherence tomography with volumetric slabs positioned at the level of the HFL. RESULTS: Optical coherence tomography data from six patients with tractional vitreoretinal pathology were reviewed. Concentric, fingerprint-like microwaves were visualized through en face optical coherence tomography in all six study eyes at the level of the HFL. This finding resembled the finding of HFL waves previously noted histopathologically from force exerted on this layer. CONCLUSION: In retinal pathologies in which specific physical forces act on the retina, volumetric optical coherence tomography may permit visualization of en face concentric, fingerprint-like hyperreflective rings within the HFL. This "fingerprint sign" may represent a biomechanical consequence of traction on the retina and allow clinical decision making based on improved recognition of the existence of such traction.

Classification of Choroidal Neovascularization Using Projection-Resolved Optical Coherence Tomographic Angiography.

Purpose: To evaluate if projection-resolved optical coherence tomographic angiography (PR-OCTA) reduces projection artifact with less attenuation of choroidal neovascularization (CNV) flow signal compared to conventional OCTA with slab subtraction. Methods: In this retrospective cross-sectional study, participants with subfoveal treatment-naïve CNV secondary to age-related macular degeneration underwent OCTA. Scans were exported for custom processing including manual segmentation as necessary, application of slab subtraction and PR-OCTA algorithm, and calculation of CNV vascular area and connectivity. CNV was classified as type 1, minimally type 2, or predominantly type 2 based on fluorescein angiography (FA) and OCT. Two masked retina specialists independently classified CNV using cross-sectional conventional OCTA and PR-OCTA. Results: A total of 17 eyes were enrolled in this study. Mean CNV vessel area (mm2) was 0.67 ± 0.51 for PR-OCTA and 0.53 ± 0.41 for slab subtraction (P = 0.018). Mean vascular connectivity was 96.80 ± 1.28 for PR-OCTA and 90.90 ± 4.42 (P = 0.018) for slab subtraction. Within-visit repeatability (coefficient of variation) of PR-OCTA was 0.044 for CNV vessel area and 0.012 for vascular connectivity, compared to 0.093 and 0.028 by slab subtraction. PR-OCTA classification agreement with FA/OCT was 88.2% and 76.5% for the two graders, while conventional OCTA agreement was 58.8% and 70.6% (grader 1, P = 0.025; grader 2, P = 0.56). Moreover, PR-OCTA enabled the individual quantification of type 1 and type 2 components of a CNV. Conclusions: PR-OCTA had greater CNV vessel area and vascular connectivity, as well as better repeatability, compared to slab subtraction, suggesting PR-OCTA is a superior technique for imaging CNV. Furthermore, PR-OCTA removes projection artifact on cross-sectional OCTA, improving the ability to classify and quantify CNV components.

Vitreous Cytokine Expression and a Murine Model Suggest a Key Role of Microglia in the Inflammatory Response to Retinal Detachment.

Purpose: Retinal detachment (RD) separates the retina from the underlying retinal pigment epithelium, resulting in a gradual degeneration of photoreceptor (PR) cells. It is known that RD also results in an inflammatory response, but its contribution to PR degeneration is unknown. In this study we examine the inflammatory responses to RD in patient vitreous and validate a mouse experimental RD as a model of this phenomenon. Methods: Multiplex bead arrays were used to examine cytokine levels in vitreous samples from 24 patients with macula-off rhegmatogenous retinal detachment (RRD) undergoing reattachment surgery and from 10 control patients undergoing vitrectomy for vitreous opacities or epiretinal membrane. Activation of the innate immune response was then examined in a mouse model of RD. Results: Twenty-eight factors were significantly increased in vitreous from RD patients versus controls. Notable were the cytokines MCP-1 (CCL2), IP-10 (CXCL10), fractalkine (CX3CL1), GRO (CXCL1), MDC (CCL22), IL-6, and IL-8, which all exhibited relatively high concentrations and several-fold increases in the vitreous of RD patients. Concentrations of various analytes correlated with a range of clinical variables such as duration of detachment and visual acuity. Retinal detachment in the mouse resulted in cytokine mRNA expression changes consistent with human RD vitreous results, as well as microglial proliferation and migration toward the outer retina. Conclusions: The findings suggest that an inflammatory response involving microglia is a component of the reaction to retinal detachment that may impact visual acuity after surgical repair and that mouse experimental RD can serve as a model to study this effect.

Aspergillus Endophthalmitis Resulting in Development of Retinal Aspergilloma.

A 78-year-old immunocompetent man presented with a 3-month history of painless decreased vision and panuveitis with a macular lesion presumed to be due to endogenous endophthalmitis. He had been treated with systemic, intravenous, and intravitreal antibiotics and antifungal agents as well as intravitreal steroids. A culture from a prior vitrectomy had grown a single colony of Aspergillus thought to be a contaminant. The macular lesion enlarged and caused a tractional retinal detachment. The patient underwent surgery including resection of what appeared to be an invasive retinal aspergilloma, from which polymerase chain reaction and histopathology confirmed Aspergillus fumigatus. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:680-683.].

Formation of an Intraretinal Fluid Barrier in Cavitary Optic Disc Maculopathy.

PURPOSE: Cavitary optic disc maculopathy develops when fluctuating pressure gradients along anomalous communications in the optic nerve head induce migration of fluid into the adjacent retinal tissue. We sought to determine whether carefully titrated laser photocoagulation combined with vitrectomy and gas tamponade can safely create an effective intraretinal barrier to fluid egress from the optic disc cavitation. DESIGN: Retrospective interventional case series. METHODS: We retrospectively evaluated medical records and imaging studies of 22 consecutive patients with cavitary disc maculopathy evaluated by a single surgeon between 1991 and 2014. Patients requiring surgery underwent carefully titrated juxtapapillary laser photocoagulation followed immediately by vitrectomy and gas tamponade. Main outcome measures were change in visual acuity, macular fluid resolution, and recurrence of maculopathy. RESULTS: Eleven patients (11 eyes) had undergone vitreous surgery and were included in the study. No preoperative evidence for vitreous traction on the optic disc or macula was seen in any eye. Nine patients underwent a single surgery and 2 patients required additional procedures to resolve the macular fluid. Mean length of follow-up after the last surgery was 48.2 months (range, 4-143 months). All 11 patients (100%) had complete resolution of macular fluid, with an average time to resolution of 8.5 months (range, 1-18 months). Only 1 of 11 patients (9%) had recurrence of macular fluid (14 months postoperatively). The average preoperative visual acuity of 20/125 (logMAR 0.81, standard deviation [SD] = 0.36) improved by nearly 4 lines to an average final visual acuity of 20/57 (logMAR 0.45, SD = 0.37) (P = .0072). A possible laser-induced central scotoma was suspected in only 1 patient who had undergone extensive prior laser treatments. CONCLUSIONS: An effective intraretinal barrier to fluid migration from cavitary optic disc anomalies can be safely achieved in most patients with carefully titrated juxtapapillary laser photocoagulation combined with vitrectomy and gas tamponade. Once achieved, the barrier facilitates resolution of macular fluid and long-term avoidance of recurrent maculopathy.

Therapeutic temperature management (TTM): post-resuscitation care for adult cardiac arrest, with recommendations from the National TTM Workgroup

Therapeutic temperature management (TTM) was strongly recommended by the 2015 International Liaison Committee on Resuscitation as a component of post-resuscitation care. It has been known to be effective in improving the survival rate and neurologic functional outcome of patients after cardiac arrest. In an effort to increase local adoption of TTM as a standard of post-resuscitation care, this paper discusses and makes recommendations on the treatment for local providers.

Muscle-sparing blepharoplasty: a prospective left-right comparative study.

BACKGROUND: Standard upper blepharoplasty involves removal of both the skin and a portion of the underlying orbicularis oculi muscle. The senior author had observed sluggishness of eyelid closure, lagophthalmos as well as varying degrees of eye irritation in certain patients during the early postoperative period. He postulated that these findings could be due to orbicularis muscle excision. He therefore undertook a prospective study 27 years ago comparing standard blepharoplasty on one eyelid to skin-only excision on the fellow eyelid. METHODS: A randomized, prospective, single-blinded study was designed using the fellow eye as an internal control. 22 patients undergoing upper blepharoplasty procedure requiring greater than 5 mm of skin resection and with no history of ophthalmologic disease, dry eye, or previous eyelid surgery were selected. Upper blepharoplasty was performed with skin-only removal on one side, and combined skin-muscle removal on the other side. Patients were evaluated until six months after surgery except for two patients who were lost to follow-up after three months. Sluggish eyelid closure, lagophthalmos, dry eye and aesthetic result were outcome measures scored by patient survey, the operating surgeon, and a blinded expert panel. RESULTS: There were comparable aesthetic outcomes in both eyelids. The incidence of sluggish eyelid closure, lagophthalmos and dry eye syndrome were significantly higher in eyelids where wide segments of muscle had been resected. CONCLUSIONS: Muscle-sparing upper blepharoplasty produces similar aesthetic outcomes as conventional blepharoplasty, while significantly reducing the complications of sluggish eyelid closure, lagophthalmos and dry eye disease. The authors therefore recommend muscle-sparing upper blepharoplasty.

Vitreoretinal surgery in the setting of permanent keratoprosthesis.

OBJECTIVES: To evaluate the surgical management of vitreoretinal pathology in patients with a permanent Boston Type 1 keratoprosthesis (hereafter referred to as a KPro) in the era of small-gauge vitrectomy techniques. METHODS: Retrospective review of 23 small-gauge vitreoretinal surgical procedures during or after Dohlman-Doane KPro placement in 14 eyes. RESULTS: Established and innovative techniques were used, including sutureless small-gauge vitrectomy, temporal positioning of surgeon, long-term tamponades, and exploratory endoscopy. Retro-KPro membranes formed less frequently when vitrectomy was performed during KPro placement. Anatomical goals were achieved, and no serious complications directly resulted from these techniques. Visual acuity, frequently limited by preexisting pathology, improved in most cases. CONCLUSIONS: Modern posterior segment surgical techniques, including small-gauge sutureless vitrectomy, can be effectively used for patients with a permanent KPro. Vitrectomy and glaucoma tube revision by a team of subspecialists at the time of KPro placement may reduce subsequent complications.

Surface epithelialization of the type I Boston keratoprosthesis front plate: immunohistochemical and high-definition optical coherence tomography characterization.

BACKGROUND: The aim of this work is to characterize a transparent tissue layer partially covering the anterior surface of the type I Boston permanent keratoprosthesis front plate in four patients. METHODS: The tissue over the front plate was easily scrolled back as a single transparent layer using a sponge. In two cases, histopathologic analysis was undertaken and immunofluorescent staining with a cytokeratin 3-specific antibody was performed. The relationship of the tissue to the keratoprosthesis device was further characterized using spectral domain high-definition optical coherence tomography (HD-OCT). RESULTS: Histopathologic analysis revealed the tissue to be non-keratinized squamous epithelium. No goblet cells were seen, suggesting the cells were of corneal, and not conjunctival, epithelial origin. Immunofluorescent staining of all cells was positive for cytokeratin 3, a protein strongly associated with corneal epithelium. The tissue was easily discerned by HD-OCT and was of substantial thickness near the external junction between the keratoprosthesis device and the carrier corneal tissue. In three cases, visual acuity was unaffected by the presence or absence of this tissue. In one case, a prominent tissue margin temporarily obscured the visual axis and reduced visual acuity; this resolved with mechanical central debridement and has not recurred. CONCLUSIONS: The transparent tissue layer covering the anterior surface of the type I Boston keratoprosthesis front plate was found to represent non-keratinized squamous epithelium, most likely of corneal epithelial origin. This potentially represents a further step in bio-integration of the keratoprosthesis device. In particular, epithelial coverage of the critical junction between the device and the carrier corneal tissue might serve an important barrier function and further reduce the incidence of infection and extrusion of the type I Boston permanent keratoprosthesis.

Specific replication origins promote DNA amplification in fission yeast.

To ensure equal replication of the genome in every eukaryotic cell cycle, replication origins fire only once each S phase and do not fire after passive replication. Failure in these controls can lead to local amplification, contributing to genome instability and the development of cancer. To identify features of replication origins important for such amplification, we have investigated origin firing and local genome amplification in the presence of excess helicase loaders Cdc18 and Cdt1 in fission yeast. We find that S phase controls are attenuated and coordination of origin firing is lost, resulting in local amplification. Specific origins are necessary for amplification but act only within a permissive chromosomal context. Origins associated with amplification are highly AT-rich, fire efficiently and early during mitotic S phase, and are located in large intergenic regions. We propose that these features predispose replication origins to re-fire within a single S phase, or to remain active after passive replication.

Cyclin-dependent kinase inhibits reinitiation of a normal S-phase program during G2 in fission yeast.

To achieve faithful replication of the genome once in each cell cycle, reinitiation of S phase is prevented in G(2) and origins are restricted from refiring within S phase. We have investigated the block to rereplication during G(2) in fission yeast. The DNA synthesis that occurs when G(2)/M cyclin-dependent kinase (CDK) activity is depleted has been assumed to be repeated rounds of S phase without mitosis, but this has not been demonstrated to be the case. We show here that on G(2)/M CDK depletion in G(2), repeated S phases are induced, which are correlated with normal G(1)/S transcription and attainment of doublings in cell size. Mostly normal mitotic S-phase origins are utilized, although at different efficiencies, and replication is essentially equal across the genome. We conclude that CDK inhibits reinitiation of S phase during G(2), and if G(2)/M CDK is depleted, replication results from induction of a largely normal S-phase program with only small differences in origin usage and efficiency.

The role of surgery in high-grade glioma--is surgical resection justified? A review of the current knowledge

<p><b>INTRODUCTION</b>The aims of this article were to review the role of surgical resection in the management of high-grade gliomas and to determine whether there is any survival benefit from surgical resection.</p><p><b>METHODS</b>A literature review of the influence of surgical resection on outcome was carried out. Relevant original and review papers were obtained through a PubMed search using the following keywords: glioma, resection, prognosis and outcome.</p><p><b>RESULTS</b>Presently, there is a lack of evidence to support a survival benefit with aggressive glioma resection, but this should not detract patients from undergoing surgery as there are many other clinical benefits of glioma excision. In addition, limiting surgical morbidity through the use of adjuvant techniques such as intraoperative magnetic resonance imaging (MRI), functional MRI and awake craniotomy is becoming increasingly important.</p><p><b>CONCLUSIONS</b>Ideally, a randomised controlled trial would be the best way to resolve the issue of whether (and to what extent) surgical resection leads to improvements in patient outcome and survival, but this would not be ethical. The second best option would be well-controlled retrospective studies with a multivariate analysis of all potential confounding factors.</p>

Phosphorylation of the RGS protein Sst2 by the MAP kinase Fus3 and use of Sst2 as a model to analyze determinants of substrate sequence specificity.

Previously, we used mass spectrometry to demonstrate pheromone-stimulated phosphorylation of Ser-539 in Sst2, a regulator of G protein signaling in yeast Saccharomyces cerevisiae [Garrison, T. R., et al. (1999) J. Biol. Chem. 274, 36387-36391]. Here, we show that Sst2 phosphorylation is mediated by the mitogen-activated protein (MAP) kinase Fus3. Phosphorylation occurs within a canonical MAP kinase phosphorylation site (Pro-X-Ser/Thr-Pro, where "X" at the -1 position can be any amino acid), a consensus sequence deduced earlier from analysis of synthetic peptide substrates. In a direct test of the model, we compared Sst2 phosphorylation following systematic substitution of the -1 residue His-538. Each of the substitution mutants was suitable as a MAP kinase substrate, as shown by phosphorylation-dependent mobility shifts in vivo and/or by direct phosphorylation in vitro followed by peptide mapping and mass spectrometry sequencing. This analysis documents phosphorylation of Sst2 by Fus3 and demonstrates that the prevailing model for MAP kinase recognition is valid for a native substrate protein in vivo as well as for small synthetic peptides tested in vitro.