Summary: Antagonistic interactions between center and surround regions of the receptive field are widely observed across sensory systems. In the early visual system, these interactions contribute to important computations such as edge detection. However, less is known about how center-surround interactions depend on the spatiotemporal properties of the visual input. Here, we show that surround motion strongly modulates the response properties of two understudied primate ganglion cell types. Broad thorny cell responses are strongest when motion in the center and surround is uncorrelated, similar to object-motion-sensitive cells found in other species. A different pattern is observed in On smooth monostratified cells: surround activation is suppressive for static stimuli and facilitatory for motion. These effects of surround activation diverge significantly from classical center-surround models and more closely resemble how surround motion affects responses in primate visual cortex.
Asma K. Alzuabi, Faris M. Al Ghulaiga, Ahmed M. Abu El-Asrar
Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of hyperinflammation. It is categorized into a primary or secondary form. Familial HLH is considered a subset of primary HLH that results from a biallelic mutation in one of the four genes that regulate granule-dependent cytotoxicity: PRF1, UNC13D, STX11, and STXBP2. The reported ocular findings in association with HLH are diverse and variable, with few reports in particular in patients with primary HLH. As far as our knowledge goes, this is the first documented instance of a genetically confirmed case of PRF1-associated familial HLH with this specific presentation. Case presentation A previously healthy 11-year-old boy presented with a one-week history of acute esotropia. A dilated fundus exam revealed peripheral snowballs with multiple areas of perivascular sheathing bilaterally with corresponding focal vascular leakage on fundus fluorescein angiography (FFA). Complete systemic workup, including brain magnetic resonance imaging (MRI), showed hyperintensities involving brain parenchyma, cerebellum, and a short spinal cord segment. The neurological exam and lumbar puncture results were within normal at that time. However, later on, the patient presented with progressively worsening systemic manifestations, including ataxic gait, dysarthria, and upper and lower limb weakness. Multiple treatment regimens were initiated without significant improvement, including intravenous methylprednisolone, intravenous immunoglobulins, and plasma exchange. Whole-exome sequencing (WES) revealed a pathogenic homozygous missense mutation (c.1081 A > T p.(Arg361Trp)) in the PRF1 gene, confirming the diagnosis of familial hemophagocytic lymphohistiocytosis. HLH treatment protocol was initiated, and the patient was transferred to another center for a hematopoietic stem cell transplantation (HSCT). Conclusion This report describes a case of PRF1-associated familial HLH with unusual initial ocular presentation, highlighting the importance of a thorough systemic workup and the consideration of this rare diagnosis for such findings.
Mihai Adrian Păsărică, Paul Filip Curcă, Marian Burcea
et al.
(1) Background: Uveal malignant melanoma is the most common adult eye cancer and presents metabolic reprogramming that affects the tumoral microenvironment by altering the redox balance and producing oncometabolites. (2) Methods: The study prospectively evaluated patients undergoing enucleation surgery or stereotactic radiotherapy for uveal melanoma by following systemic oxidative-stress redox markers serum lipid peroxides, total albumin groups and total antioxidant levels (3) Results: Serum antioxidants and lipid peroxides were elevated from pre-treatment to longer-term follow-up. Antioxidants inversely correlated to lipid peroxides: higher in stereotactic radiosurgery patients pre/6/12/18 months post-treatment (<i>p</i> = 0.001–0.049) versus higher lipid peroxides in enucleation surgery patients pre/after/6 months post-treatment (<i>p</i> = 0.004–0.010). An increased variance in serum antioxidants was observed for enucleation surgery patients (<i>p</i> < 0.001), however enucleation did not increase mean serum antioxidants or albumin thiols; only lipid peroxides were increased post-enucleation (<i>p</i> < 0.001) and at 6-month follow-up (<i>p</i> = 0.029). Mean albumin thiols were increased for 18- and 24-month follow-ups (<i>p</i> = 0.017–0.022). Males who had enucleation surgery presented higher variance in serum determinations and overall higher lipid peroxides values pre/post-treatment and at the 18-month follow-up. (4) Conclusions: Initial oxidative stress-inducing events of surgical enucleation or stereotactic radiotherapy for uveal melanoma are followed by a longer-term inflammatory cascade gradually subsiding at later follow-ups.
Matthew Boyko, Benjamin F. Gruenbaum, Ilan Shelef
et al.
Abstract Traumatic brain injury (TBI) affects millions of people worldwide, many of whom are affected with post-TBI mood disorders or behavioral changes, including aggression or social withdrawal. Diminished functionality can persist for decades after TBI and delay rehabilitation and resumption of employment. It has been established that there is a relationship between these mental disorders and brain injury. However, the etiology and causal relationships behind these conditions are poorly understood. Rodent models provide a helpful tool for researching mood disorders and social impairment due to their natural tendencies to form social hierarchies. Here, we present a rat model of mental complications after TBI using a suite of behavioral tests to examine the causal relationships between changes in social behavior, including aggressive, hierarchical, depressive, and anxious behavior. For this purpose, we used multivariate analysis to identify causal relationships between the above post-TBI psychiatric sequelae. We performed statistical analysis using principal component analysis, discriminant analysis, and correlation analysis, and built a model to predict dominant-submissive behavior based on the behavioral tests. This model displayed a predictive accuracy of 93.3% for determining dominant-submissive behavior in experimental groups. Machine learning algorithms determined that in rats, aggression is not a principal prognostic factor for dominant-submissive behavior. Alternatively, dominant-submissive behavior is determined solely by the rats’ depressive-anxious state and exploratory activity. We expect the causal approach used in this study will guide future studies into mood conditions and behavioral changes following TBI.
BACKGROUND: Subretinal hyperreflective material (SHRM) is a hyperreflective material seen on optical coherence tomography (OCT) and located under the retina and above the retinal pigment epithelium. This study aims to examine the effect of SHRM on the functional prognosis of age-related macular degeneration (AMD) patients who switched from intravitreal ranibizumab to intravitreal aflibercept treatment.
MATERIALS AND METHODS: This is a retrospective, nonrandomized clinical study. AMD patients meeting the switching criteria underwent a complete ophthalmic examination, including spectral-domain OCT and fundus fluorescein angiography. The best-corrected visual acuity and OCT parameters were measured at the switch and 3, 6, 12, and 24 months after. SHRM(+/−), maximum SHRM thickness, and subjective and objective reflectivity stages of SHRM (grades 1–3) were evaluated.
RESULTS: SHRM was observed in 24/48 (50.0%) of eyes at the time of the switch. The differences in maximum SHRM thicknesses were not statistically significant. SHRM's mean subjective reflectivity stages at the switch and subsequent examinations were 2.37, 2.75, 2.75, 2.74, and 2.81; SHRM's objective reflectivity staging also confirmed them. Functional changes after the switch showed a significant VA loss in the SHRM(+) group and significant gain in the SHRM(−) group.
CONCLUSION: This study showed that the presence of SHRM and higher optical reflectivity at the switch from ranibizumab to aflibercept caused a poor prognosis after the switch. On the other hand, SHRM(−) patients achieved good functional results after the switch.
Adrien Quintin, Loïc Hamon, Fidelis A. Flockerzi
et al.
Abstract Background Epithelial ingrowth is a rare complication after ocular perforation and can become manifest many years after the primary trauma. Case presentation A 49-year-old patient presented with a positive Seidel test of unclear origin at her left eye, as well as a sharply defined anterior-stromal corneal scar at both eyes. Prior operations included a bilateral laser-assisted blepharoplasty 3 months earlier. The patient indicated to have been on holiday to France 5 months earlier, during an ongoing oak processionary moth caterpillars infestation. The examination using confocal microscopy confirmed a corneal perforation at the left eye and revealed corneal epithelial ingrowth capped with scarred stroma in both eyes. We performed a penetrating keratoplasty at the left eye. The scarred and perforated host cornea was divided into 4 pieces for further investigation: microbiology (negative), virology (negative), histology and transmission electron microscopy (TEM). Histology revealed differently structured epithelium, centrally inverted into the stroma through defects in Bowman’s layer. TEM revealed full thickness corneal perforation with an epithelial plug extending to the lower third of the cornea, but without evidence of epithelial cell migration into the anterior chamber. Our differential diagnosis of the unclear positive Seidel test with epithelial ingrowth was as follows: (1) corneal perforation by hairs of the oak processionary moth caterpillar, although no hairs could be found histologically; (2) corneal perforation during laser-assisted blepharoplasty, which may be supported by the presence of pigmented cells on the posterior surface of Descemet´s membrane, pointing to a possible iris injury. Conclusion Consequently, we highlighted that contact lenses can be useful, safe and inexpensive protective devices in upper eyelid procedures to protect the cornea against mechanical iatrogenic trauma.
Aging affects almost all the aspects of brain functions, but the mechanisms remain largely undefined. Increasing number of literatures have manifested the important role of glial cells in regulating the aging process. Oligodendroglial lineage cell is a major type of glia in central nervous system (CNS), composed of mature oligodendrocytes (OLs), and oligodendroglia precursor cells (OPCs). OLs produce myelin sheaths that insulate axons and provide metabolic support to meet the energy demand. OPCs maintain the population throughout lifetime with the abilities to proliferate and differentiate into OLs. Increasing evidence has shown that oligodendroglial cells display active dynamics in adult and aging CNS, which is extensively involved in age-related brain function decline in the elderly. In this review, we summarized present knowledge about dynamic changes of oligodendroglial lineage cells during normal aging and discussed their potential roles in age-related functional decline. Especially, focused on declined myelinogenesis during aging and underlying mechanisms. Clarifying those oligodendroglial changes and their effects on neurofunctional decline may provide new insights in understanding aging associated brain function declines.
Himabindu Adusumilli, Lakshmi Krupa, Nitin S Shetty
et al.
To report an unusual case of a 71-year-old livestock farmer with systemic brucellosis and ocular involvement. Examination showed vitreous haze with bilateral serous choroidal detachment. He was treated with topical antibiotics and corticosteroids, Tab rifampicin 600 mg and doxycycline 100 mg for 6 weeks with visual recovery and complete resolution of serous choroidal detachment in 2 weeks. This is the first case of bilateral serous choroidal detachment in a case of systemic brucellosis. Immune-mediated complex and direct microbial invasion of uveal tissue leading to serous choroidal detachment is the proposed pathogenesis that responds well to topical corticosteroids.
The dressing material of a wound plays a key role since bacteria can live in the bandage and keep re-infecting the wound, thus a bandage is needed that blocks biofilm in the bandage. Using an in vivo wound biofilm model, we examined the effectiveness of an organo-selenium (OS)-coated polyester dressing to inhibit the growth of bacteria in a wound. <i>Staphylococcus aureus</i> (as well as MRSA, Methicillin resistant <i>Staph aureus</i>), <i>Stenotrophomonas maltophilia</i>, <i>Enterococcus faecalis</i>, <i>Staphylococcus epidermidis</i>, and <i>Pseudomonas aeruginosa</i> were chosen for the wound infection study. All the bacteria were enumerated in the wound dressing and in the wound tissue under the dressing. Using colony-forming unit (CFU) assays, over 7 logs of inhibition (100%) was found for all the bacterial strains on the material of the OS-coated wound dressing and in the tissue under that dressing. Confocal laser scanning microscopy along with IVIS spectrum in vivo imaging confirmed the CFU results. Thus, the dressing acts as a reservoir for a biofilm, which causes wound infection. The same results were obtained after soaking the dressing in PBS at 37 °C for three months before use. These results suggest that an OS coating on polyester dressing is both effective and durable in blocking wound infection.
Schouten, Ike, Goel, Sugandha, Saurabh, Kumar
et al.
Concurrent macular telangiectasia type 2 (MacTel) and branch retinal vein occlusion (BRVO) have not been described before and can pose a diagnostic dilemma. The current report highlights the role of multicolour (MC) imaging and blue reflectance (BR) imaging in diagnosing this multi-pathology. A 60-year-old male presented with diminution of vision in the right eye. BR imaging showed parafoveal hyperreflectance, characteristic of MacTel, and hyperreflective parafoveal retinal vessels indicating vascular changes in RVO. MC imaging, particularly the BR component is a promising tool to aide in the diagnosis of concurrent MacTel and BRVO, guiding treatment decisions and prognosticating treatment outcomes.
A 4-year-old child with B-cell acute lymphoblastic leukemia presented with vitreous hemorrhage due to proliferative retinopathy in both eyes. Pars plana vitrectomy was performed in both eyes to clear nonresolving vitreous hemorrhage after systemic stabilization. Visual recovery was limited by the disc drag in the right eye and subfoveal exudation in the left eye. Etiopathogenesis and management of proliferative retinopathy in acute leukemias are discussed.
Purpose. To quantify macular vascular density using optical coherence tomography angiography (OCTA) and to investigate its relationship with retinal thickness in myopic eyes of young adults. Methods. In this cross-sectional study, 268 myopic eyes without pathological changes were recruited and divided into three groups: mild myopia (n=81), moderate myopia (n=117), and high myopia (n=70). Macular vascular density was quantified by OCTA and compared among three groups. Average retinal thickness, central subfield thickness, and macular ganglion cell complex (mGCC) thickness were also evaluated and compared. Correlations among these variables were analyzed. Results. There was no statistical difference in superficial (62.3 ± 5.7% versus 62.7 ± 5.9% versus 63.8 ± 5.5%) and deep macular vascular densities (58.3 ± 9.6% versus 59.2 ± 9.3% versus 60.9 ± 7.9%) among mild-myopia, moderate-myopia, and high-myopia groups (both P>0.05). Superficial and deep macular vascular densities both had correlations with mean arterial pressure. Furthermore, superficial macular vascular density was significantly correlated with mGCC thickness. Conclusions. Varying degrees of myopia did not affect macular vascular density in young healthy adults. In addition, superficial macular vascular density, as an independent factor, was positively correlated with mGCC thickness.
Ashraf Ahmed Nossair, Wael Ahmed Ewais, Lamia Samy Ali
Purpose. To evaluate the technique of vitreous tap using needle aspiration for management of anterior chamber shallowness during phacoemulsification. Methods. A retrospective study included 26 eyes of 17 patients who underwent phacoemulsification in which vitreous tap was performed using a 27-gauge needle attached to a 5 ml syringe, inserted 3.5 mm from the limbus to aspirate 0.2 ml of liquefied vitreous if a cohesive (OVD) failed to sufficiently deepen the anterior chamber. Results. Preoperative anterior chamber depth was 2.31 ± 0.26 mm, axial length was 21.7 ± 0.67 mm, lens thickness was 4.5 ± .19 mm, and cataract grade was 3.77 ± 1.4. Preoperative CDVA in LogMAR units was 0.98 ± 0.75. Coexisting angle closure glaucoma was present in 7 patients (26.92%) preoperatively. Vitreous needle tap was successful in vitreous removal on the first attempt in 26 eyes (100%). Postoperative follow-up period was 22.88 ± 10.24 (4–39) months. The final postoperative CDVA in LogMAR units was 0.07 ± 0.1, while the final postoperative IOP was 16.54 ± 1.45 mmHg. No complications related to vitreous tap were noted. Conclusion. Vitreous needle tap is a simple, cost-effective, and safe technique for management of shallow anterior chamber in phacoemulsification.
Objectives: Evaluation of structural alterations of the optic nerve head (ONH) and the retinal nerve fiber layer (RNFL) in patients with
ocular hypertension (OHT) and early-stage glaucoma and assessment of the discriminatory diagnostic performance of spectral-domain
optical coherence tomography (SD-OCT) Copernicus (Optopol Technology S.A.).
Materials and Methods: This study included 59 eyes of a total of 59 patients, 29 of whom were diagnosed with OHT (Group 1) and
30 with early-stage glaucoma (Group 2). The differentiation of early-stage glaucoma and OHT was carried out on the basis of standard
achromatic visual field test results. Analysis of the ONH and RNFL thickness of all cases was made using SD-OCT. Group 1 and Group
2 were compared with respect to the ONH parameters and RNFL thickness. The diagnostic sensitivity of the OCT parameters was
evaluated by the area under the receiver operating characteristics curves (AUC).
Results: The average, superior, inferior, and nasal RNFL thicknesses in early-stage glaucoma cases were approximately 10% (12-14
µm) less compared to the OHT eyes, with differences being highly significant (p≤0.001). However, there was no statistically significant
difference in the temporal RNFL thicknesses. The most sensitive parameter in the early diagnosis of glaucoma was average RNFL
thickness corresponding to AUC: 0.852, followed by AUC: 0.816 and AUC: 0.773 values in superior and inferior RNFL thickness,
respectively. In localized RNFL defects, the highest sensitivity corresponded to superior and superonasal quadrants (ACU: 0.805 and
ACU: 0.781, respectively). There were not any statistically significant differences between the ONH morphological parameters of the
two groups.
Conclusion: RNFL analysis obtained using SD-OCT Copernicus is able to discriminate early-stage glaucoma eyes from those with
OHT. However, ONH morphological parameters do not have the same diagnostic sensitivity. Turk J Ophthalmol 2014; 44: 35-41)
Masasko Kuroda,1 Akihiro Nishida,1 Masashi Kikuchi,2 Yasuo Kurimoto11Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan; 2Kikuchi Eye Clinic, Kobe, Hyogo, JapanAbstract: We report the case of a 66-year-old Japanese man who developed neovascular glaucoma secondary to Purtscher's retinopathy following a head injury. The patient presented at our hospital with blurred vision and a visual field abnormality in his left eye 1 month after suffering from a head injury. Upon initial presentation, his best-corrected visual acuity on a decimal chart was 1.5 oculus dexter and 0.6 oculus sinister. The intraocular pressure (IOP) was 12 mmHg in both eyes. Fundus examination of the left eye revealed multiple white lesions in the posterior pole. Optical coherence tomography demonstrated retinal edema, particularly in the inner retina. On the basis of these findings, a diagnosis of Purtscher's retinopathy was made. One month after the initial examination, the visual acuity in the left eye deteriorated to 0.01 in decimal chart, and the IOP increased to 37 mmHg. Gonioscopy showed angle neovascularization. The patient received an intravitreal bevacizumab injection and panretinal photocoagulation. Subsequently, the IOP normalized and the angle neovascularization regressed.Keywords: blurred vision, visual field, retinal edema, head injury, head trauma
V.I. Konenkov,, V.V. Klimontov, A.V. Shevchenko
et al.
ABSTRACT
Purpose. To study the association of single nucleotide polymorphism (SNP) combinations of cytokine genes (IL1B, IL4, IL6, IL10, TNFA, VEGF) and matrix metalloproteinase genes (MMP2, MMP3, MMP9) with diabetic retinopathy (DR) in patients with type 2 diabetes (T2D).
Material and methods. There were examined 103 Caucasoid females with T2D aged 50 to 70 years, including 49 with and 54 without DR. There were studied 13 SNPs in the promoter regions of following genes: VEGF: А2578С and С936Т; IL1В: С31Т; IL4: С590Т; IL6: G174C; IL10: A592C and А1082G; TNFА: А238G, A308G and A863C; MMP2: T1306C; ММР3: 5A/6A; MMP9: С1562T. Genotyping was performed by the method of restriction fragment length polymorphism.
Results. There were revealed 37 SNP combinations positively associated with DR and 11 negatively associated combinations.
DR-associated combinations included homozygous variants of VEGF (936CC), TNFA (308GG and 238GG), IL1B (31TT), IL4 (590CC), IL10 (592CC) and MMP9 (1592CC). In combinations negatively associated with DR there were heterozygous genotypes of TNFA (308GA) and IL10 (1082AG), and homozygous genotypes of IL1B (31CC), MMP2 (1306CC) and MMP3 (6A/6A).
Conclusions. The variants of these genes may determine a susceptibility/resistance to DR, influencing the intensity of inflammation and angiogenesis in the retina
Martin Roesel1, Christoph Tappeiner2, Arnd Heiligenhaus1,3, Carsten Heinz1,31Department of Ophthalmology, St Franziskus-Hospital, Muenster, Germany; 2Department of Ophthalmology, Inselspital, University of Bern, Switzerland; 3University Duisburg-Essen, GermanyAbstract: Voclosporin, a novel immunomodulatory drug inhibiting the calcineurin enzyme, was developed to prevent organ graft rejection and to treat autoimmune diseases. The chemical structure of voclosporin is similar to that of cyclosporine A, with a difference in one amino acid, leading to superior calcineurin inhibition and less variability in plasma concentration. Compared with placebo, voclosporin may significantly reduce inflammation and prevent recurrences of inflammation in patients with noninfectious uveitis. Future studies have to show if these advantages are accompanied by greater clinical efficacy and fewer side effects compared with the classic calcineurin inhibitors.Keywords: uveitis, immunosuppression, voclosporin