Publications by authors named "Iris S Kassem"

15 Publications

  • Page 1 of 1

Quantitative proteomic analysis of aqueous humor after rabbit lensectomy reveals differences in coagulation and immunomodulatory proteins.

Mol Omics 2020 04 7;16(2):126-137. Epub 2020 Feb 7.

Cell Biology, Neurobiology, & Anatomy, Medical College of Wisconsin, The Eye Institute, 925 N. 87th Street, Milwaukee, WI 53226, USA.

Compared to adults, children experience increased postoperative scarring and inflammation following intraocular surgery. While the underlying causes of the exaggerated immune response in children are not understood, proteins play key roles in postoperative scarring and wound healing processes. To identify and quantify proteins associated with the robust postoperative immune response, this study applied quantitative proteomics approaches to a juvenile rabbit model of lensectomy with intraocular lens (IOL) insertion. Twenty-six 6-7 week-old New Zealand white rabbits underwent unilateral portions of lensectomy with IOL insertion including: anterior chamber paracentesis, corneal incision with wound suture, lensectomy only, and lensectomy with IOL insertion. Aqueous humor was collected immediately prior and three days after each procedure. Semi-quantitative protein discovery was achieved by label-free quantitation using data dependent and data independent acquisition modes. Based on the discovery results, targeted quantitation by parallel reaction monitoring of 3 proteins of interest, fibrinogen-beta chain, transforming growth factor beta-2, and retinol binding protein 3, was used to confirm the observed quantitative trends. Total protein concentration levels increased with each progressive surgical step of lensectomy with IOL insertion. Proteins related to the complement and coagulation cascades were found to increase in relative abundance, while proteins related to ocular immunosuppression decreased in abundance following surgery. These data provide insights into the postoperative response by providing the first surgical step-wise views of the AH proteome before and after surgery. Overall, this work provides the foundation for future investigations targeting specific proteins for therapeutic interventions aimed at minimizing postoperative complications after pediatric intraocular surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9mo00169gDOI Listing
April 2020

Rats deficient in α-galactosidase A develop ocular manifestations of Fabry disease.

Sci Rep 2019 06 28;9(1):9392. Epub 2019 Jun 28.

Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of α-galactosidase A. Ocular findings, such as cornea verticillata, cataracts, and retinal vascular tortuosity, serve as important diagnostic markers. We aimed to evaluate ocular phenotypes in α-galactosidase A-deficient (Fabry) rats and hypothesized that these rats would manifest ocular signs similar to those observed in patients. Slit lamp biomicroscopy was used to evaluate the cornea and lens, and retinal vasculature was examined by fluorescein angiography in WT and Fabry rats. Mass spectrometry was used to characterize and quantify ocular glycosphingolipids, and histology and electron microscopy revealed the location of the glycosphingolipid storage. We found that Fabry rats developed corneal and lenticular opacities to a statistically greater degree than WT rats. Retinal vascular morphology did not appear grossly different, but there was vascular leakage in at least one Fabry rat. Fabry rat eyes accumulated substrates of α-galactosidase A, and these α-galactosyl glycoconjugates were found in corneal keratocytes, lens fibers, and retinal vascular endothelial cells. Electron-dense lamellar inclusions were observed in keratocytes. Because Fabry rats recapitulate many ocular phenotypes observed in patients, they can be used to study disease pathogenesis and determine whether ocular findings serve as noninvasive indicators of therapeutic efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-45837-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599056PMC
June 2019

Zone of retinal vascularization and refractive error in premature eyes with and without spontaneously regressed retinopathy of prematurity.

J AAPOS 2019 08 20;23(4):211.e1-211.e6. Epub 2019 Jun 20.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois; Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address:

Purpose: To evaluate the relationship between zone of retinal vascularization and refractive error in premature infants without retinopathy of prematurity (ROP) or with spontaneously regressed ROP.

Methods: The medical records of neonates screened for ROP between 2009 and 2015 at a tertiary academic center were reviewed retrospectively. Cases included untreated eyes with spontaneously regressed ROP; premature eyes without a diagnosis of ROP were control subjects. Primary outcomes were zone of retinal vascularization and refractive error, determined by cycloplegic retinoscopy (CR).

Results: Of 378 eyes evaluated, 184 had ROP, 24 of which underwent treatment and were excluded. Mean corrected age at first CR was 7.5 months. Seventeen eyes without ROP were myopic at first CR (8.8%), compared to 35 eyes with regressed ROP (21.9%). No untreated eyes had halted vasculature in zone I; notably, 44% of spontaneously regressed zone II eyes were myopic. Irrespective of ROP status, CR significantly differed by zone of vascularization (P < 0.001), with more myopia occurring with posterior halting of vascularization. For all eyes, CR significantly differed between complete vascularization versus zone II (P < 0.0001) and zone III versus zone II (P = 0.001); zone III versus complete vascularization did not statistically differ (P = 0.15). This relationship held true for untreated, spontaneously regressed ROP eyes (P < 0.01, P = 0.01, P = 0.8343).

Conclusions: More myopic refraction occurred in neonates screened for ROP with posterior halting of vascularization. Patients with halted vascular growth in zone II should be closely monitored for myopia and refractive amblyopia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaapos.2019.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778011PMC
August 2019

Sustained Anti-Vascular Endothelial Growth Factor Activity of Aflibercept (Eylea) After Storage in Polycarbonate Syringes Used for Intravitreal Injection: A Pathway to Safety and Efficiency.

J Ocul Pharmacol Ther 2019 06 27;35(5):278-282. Epub 2019 Mar 27.

Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin.

Aflibercept (Eylea™, Regeneron) is supplied in single-use glass vials along with 1 cc polycarbonate syringes. We sought to determine if storage of aflibercept for sustained periods within these syringes would result in loss of antivascular endothelial growth factor (anti-VEGF) activity. Aflibercept samples were drawn from commercially available glass vials into manufacturer-supplied 1-mL syringes and stored at 4°C. Anti-VEGF activity was assessed using enzyme-linked immunosorbent assays at the following storage durations: 0, 4, 9, 14, and 28 days. Frozen samples stored at -20°C for 28 and 56 days were also assayed. Also, a subset of aflibercept samples was stored and then diluted to 1:10 and progressively smaller concentrations and the assays repeated. Aggregation of aflibercept was tested using a dynamic light scattering assay. There were no statistical differences in anti-VEGF activity among aflibercept samples of 1:1 or 1:10 dilution stored at either 4°C or -20°C at any of the storage intervals ( > 0.05). We also observed persistence of robust anti-VEGF activity for up to 14 days when diluted poststorage to 1:16,000, a concentration that would be expected after >7 vitreous half-lives within the eye (estimated at >50 days). No evidence of drug aggregation in specimens stored for 14 days was observed. Our findings support feasibility of prefilling and storage of aflibercept within manufacturer-supplied polycarbonate syringes for as long as 14 days before use under pharmacy-based sterile conditions, facilitating greater safety and efficiency in many clinics delivering anti-VEGF therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jop.2018.0085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588124PMC
June 2019

Use of a Juvenile Rabbit Animal Model to Evaluate Therapeutic Interventions for Postoperative Inflammation and Fibrin Formation After Lensectomy.

Transl Vis Sci Technol 2019 Jan 9;8(1). Epub 2018 Jan 9.

Department of Ophthalmology, University of Illinois-Chicago, Chicago, IL, USA.

Purpose: We used the juvenile rabbit as a model for investigating therapeutic interventions for postoperative inflammation and fibrin formation following intraocular lens (IOL) insertion for management of pediatric cataracts.

Methods: Twelve 6- to 7-week-old, 600 to 900 g rabbits underwent bilateral clear-cornea lensectomy via irrigation and aspiration with IOL insertion. Following wound closure, enoxaparin 8 mg ( = 6 eyes), preservative-free triamcinolone 0.5 mg ( = 6), 8 mg enoxaparin plus 0.5 mg triamcinolone ( = 6), or balanced salt solution ( = 6) was injected into the anterior chamber. Slit-lamp examinations and optical coherence tomography (OCT) scans were performed postoperatively on days 3 through 7, and 14 to characterize levels of inflammation and fibrin. Using 17 additional rabbits, enzyme-linked immunosorbent assays (ELISAs) with 100 μL of aqueous humor were performed to quantify the amount of fibrinogen and fibrin preoperatively and on postoperative day 3. Immunohistochemistry was performed to confirm the presence of fibrin.

Results: Enoxaparin alone and combined with triamcinolone reduced the amount of fibrin present in the anterior chamber compared to untreated eyes, which corresponded to an increase in OCT signal strength. Despite the clear visual axis shown in clinical images, the combination treatment group had the highest levels of soluble fibrin when assessed by ELISA. Immunohistochemistry confirmed the presence of insoluble fibrin seen clinically.

Conclusions: A combination of enoxaparin and triamcinolone appears to provide the most therapeutic benefit by reducing fibrin formation and postoperative inflammation.

Translational Relevance: The juvenile rabbit is an excellent model to investigate inflammation and fibrin formation following lensectomy with IOL insertion and possibly any intraocular surgery in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/tvst.8.1.5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327344PMC
January 2019

Acid Ceramidase Deficiency in Mice Leads to Severe Ocular Pathology and Visual Impairment.

Am J Pathol 2019 02 23;189(2):320-338. Epub 2018 Nov 23.

Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin; University Health Network, Toronto, Ontario, Canada. Electronic address:

Farber disease (FD) is a debilitating lysosomal storage disorder characterized by severe inflammation and neurodegeneration. FD is caused by mutations in the ASAH1 gene, resulting in deficient acid ceramidase (ACDase) activity. Patients with ACDase deficiency exhibit a broad clinical spectrum. In classic cases, patients develop hepatosplenomegaly, nervous system involvement, and childhood mortality. Ocular manifestations include decreased vision, a grayish appearance to the retina with a cherry red spot, and nystagmus. That said, the full effect of ACDase deficiency on the visual system has not been studied in detail. We previously developed a mouse model that is orthologous for a known patient mutation in Asah1 that recapitulates human FD. Herein, we report evidence of a severe ocular pathology in Asah1 mice. Asah1 mice exhibit progressive retinal and optic nerve pathology. Through noninvasive ocular imaging and histopathological analyses of these Asah1 animals, we revealed progressive inflammation, the presence of retinal dysplasia, and significant storage pathology in various cell types in both the retina and optic nerves. Lipidomic analyses of retinal tissues revealed an abnormal accumulation of ceramides and other sphingolipids. Electroretinograms and behavioral tests showed decreased retinal and visual responses. Taken together, these data suggest that ACDase deficiency leads to sphingolipid imbalance, inflammation, dysmorphic retinal and optic nerve pathology, and severe visual impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajpath.2018.10.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412726PMC
February 2019

Findings in Persistent Retinopathy of Prematurity.

Ophthalmic Surg Lasers Imaging Retina 2018 07;49(7):497-503

Background And Objective: To determine whether retinopathy of prematurity (ROP) that persists beyond a postmenstrual age (PMA) of 45 weeks has abnormalities that can be documented by fundus photography or fluorescein angiography (FA).

Patients And Methods: Fundus photographs and FAs were reviewed for all premature infants who underwent FA for persistent ROP after 45 weeks PMA.

Results: Of the 487 infants who were screened for ROP, 16 (3.3%) demonstrated ROP beyond 45 weeks. Seven (43.8%) infants received prior treatment with intravitreal bevacizumab (IVB) for Type 1 ROP. FAs were obtained in eight cases; four subjects were previously treated with IVB. Leakage at the vascular-avascular border was demonstrated in seven subjects (87.5%). Shunt vessels, posterior retinal nonperfusion, and absence of the foveal avascular zone was limited to the IVB group.

Conclusions: There are persistent vascular abnormalities among infants with ROP beyond 45 weeks. Findings that may be missed by RetCam fundus photographs were highlighted with FA. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:497-503.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3928/23258160-20180628-05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196355PMC
July 2018

Biometry Characteristics in Adults and Children With Marfan Syndrome: From the Marfan Eye Consortium of Chicago.

Am J Ophthalmol 2017 May 28;177:144-149. Epub 2017 Feb 28.

Northwestern University Feinberg School of Medicine, Chicago, Illinois; Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. Electronic address:

Purpose: To report on the biometric findings of adults and children with Marfan syndrome (MFS) recruited from 2 annual National Marfan Foundation conferences (2012 and 2015).

Design: Cross-sectional study.

Methods: Subjects diagnosed with MFS by Ghent 2 nosology were included for analysis. Subjects were divided into "adults" (≥16 years of age) and "children" (5-15 years of age). Biometric data included values for refractive error, axial length (AL), corneal curvature, anterior chamber depth, lens thickness, and central corneal thickness.

Results: Of the 117 subjects evaluated, 74 (35 adults, 32 children, and 7 children <5 years of age) had a definite diagnosis of MFS and were included in the study. The AL was longer (25.25 ± 0.32 mm vs 24.24 ± 0.33 mm, P = .03) and the lens was thicker (3.94 ± 0.09 mm vs 3.62 ± 0.10 mm, P = .03) in adults. Both groups had flat corneas (average keratometry [K] of 41.59 ± 0.35 diopters [D] in adults vs 40.89 ± 0.36 D in children, P = .17). A negative correlation was found between AL and K (-0.33, P < .001). The corneas of patients with MFS with ectopia lentis (EL) were significantly flatter and with higher degree of corneal astigmatism compared to patients without EL (K of 40.68 ± 0.31 D vs 41.75 ± 0.28 D, P < .01 and corneal astigmatism of 1.68 ± 0.16 D vs 1.13 ± 0.14 D, P = .01).

Conclusions: Children with established MFS have flat corneas at least to the same degree as adults. Corneas of patients with MFS with EL are flatter and have a higher degree of corneal astigmatism. We strongly suggest that corneal parameters should be measured if MFS is suspected, especially in children that may not yet have developed EL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2017.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648325PMC
May 2017

A Case Report of Ablepharon-Macrostomia Syndrome with Amniotic Membrane Grafting.

Case Rep Ophthalmol 2015 Sep-Dec;6(3):366-72. Epub 2015 Oct 30.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago College of Medicine, Chicago, Ill., USA ; Department of Ophthalmology, Medical College of Wisconsin Eye Institute, Milwaukee, Wisc., USA.

We describe a rare case of an infant who was born with multiple congenital anomalies, including the absence of eyelids. This patient had many dysmorphic features consistent with a severe phenotype of ablepharon-macrostomia syndrome (AMS) including a fish-like appearance of the mouth, rudimentary ears, absence of body hair, thin skin, absent nipples, abdominal distension, and genital abnormalities. Upon presentation, there was severe exposure keratopathy causing large bilateral sterile ulcers culminating in corneal melting of both eyes. An amniotic membrane graft was used to attempt to maintain the corneal surface integrity. However, because of the late presentation, the corneas could not be salvaged. Extensive surgical reconstruction of both eyelids and bilateral penetrating keratoplasty was ultimately performed successfully to protect the ocular surfaces while trying to maximize the visual potential. Early amniotic membrane grafting may be done at the bedside and may help preserve the ocular in patients with severe eyelid deformities until more definitive treatment is performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000441615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649710PMC
November 2015

One Year of Pediatric Ophthalmology and Strabismus Research in Review.

Asia Pac J Ophthalmol (Phila) 2013 Nov-Dec;2(6):388-400

From the *University of Illinois at Chicago Eye and Ear Infirmary, Chicago, IL; and †Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, MI.

Purpose: To highlight recent advances in amblyopia and strabismus.

Design: Literature review.

Methods: A literature search of articles published in the English language was performed in PubMed or MEDLINE between May 2012 and April 2013 using the terms amblyopia or strabismus. Articles deemed relevant were selected.

Results: The review highlights articles that increase our understanding of strabismus and amblyopia as well as newer treatment strategies.

Conclusions: The review highlights some new information and possible future advances in amblyopia and strabismus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/APO.0000000000000019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839686PMC
August 2015

Traumatic eye injuries from collapsible wire laundry hampers.

Pediatrics 2013 Aug 1;132(2):e522-5. Epub 2013 Jul 1.

University of Illinois at Chicago Eye and Ear Infirmary, Chicago, Illinois 60612, USA.

Two patients presented to the University of Illinois at Chicago Eye and Ear Infirmary within 1 year with penetrating eye injuries caused by similar collapsible cloth and wire laundry hampers. Penetrating eye injuries in children are relatively rare but can result in poor visual outcomes and multiple vision-threatening complications. Both injuries at the University of Illinois resulted in an eye laceration as well as retinal complications similar to those reported with a high velocity injury. This now represents a significant pattern of eye injury and suggests that there exists a nontrivial risk for all children in households with this type of collapsible laundry hamper. Parents should receive a warning of the risks of these hampers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2012-3169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727671PMC
August 2013

Exotropia in children with high hyperopia.

J AAPOS 2012 Oct;16(5):437-40

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.

Purpose: To describe the clinical characteristics, treatment, and subsequent clinical course of children with exotropia and high hyperopia.

Methods: The medical records of 26 patients seen between 1990 and 2009 who had an exotropia and ≥4.00 D of hyperopia were retrospectively reviewed. We analyzed the clinical characteristics, treatments, and subsequent alignment outcomes.

Results: A total of 26 patients between the ages of 2.5 months and 9 years were included. Of these, 15 had associated medical conditions or developmental delay. Of 22 patients with measured visual acuities, 19 had amblyopia (10 unilateral, 9 bilateral). None of the patients demonstrated fine stereoacuity. Twenty-three exotropic children were treated with spectacles: 15 were fully corrected, 10 of whose exotropia improved; 8 received partial correction of their hyperopia, 3 of whose exotropia improved. Six patients who presented with large, poorly controlled exotropia and did not improve with spectacle correction required strabismus surgery.

Conclusions: Children with high hyperopia and exotropia are likely to have developmental delay or other systemic diseases, amblyopia, and poor stereopsis. Treatment of high hyperopia in exotropic children with their full cycloplegic refraction can result in excellent alignment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaapos.2012.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479442PMC
October 2012

Marcus Gunn jaw winking with trigemino-oculomotor synkinesis of the inferior division of the oculomotor nerve.

J AAPOS 2009 Jun;13(3):315-6

Department of Ophthalmology, North Shore-Long Island Jewish Health System, Great Neck, New York 11021, USA.

Synkinetic aberrant innervation syndromes can involve abnormal movements of multiple extraocular and eyelid muscles. The authors describe a case of eyelid elevation associated with simultaneous adduction and depression of the eye upon chewing, sucking on a bottle, or wide opening of the mouth since birth. This represents a unique case of congenital Marcus Gunn jaw winking with trigemino-oculomotor synkinesis involving the inferior branch of the oculomotor nerve. The most likely explanation for these abnormal movements is prenatal aberrant innervation of eyelid and extraocular muscles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaapos.2009.02.004DOI Listing
June 2009

Asymmetry of blinking.

Invest Ophthalmol Vis Sci 2006 Jan;47(1):195-201

Department of Neurobiology and Behavior, SUNY Stony Brook, Stony Brook, New York 117940-5230, USA.

Purpose: Too investigate asymmetry in eyelid movements with blinking, the stability of the asymmetry, and its modifiability in normal humans.

Methods: Differences in the start time and amplitude between the two eyelids were assessed for voluntary blinks and reflex blinks evoked by supraorbital trigeminal nerve stimulation. These variables were also measured before and up to 18 months after 2 hours of unilateral upper lid restraint.

Results: With voluntary blinks, one eyelid consistently began to close earlier and made a larger eyelid movement than the other eyelid. Stimulation of the supraorbital branch of the trigeminal nerve evoked relatively larger amplitude blinks in one eyelid that correlated with the asymmetries of voluntary blinks. There was a continuum of eyelid asymmetry across all subjects that was stable and independent of other biological asymmetries, such as handedness. Briefly reducing eyelid mobility created a long-lasting change in eyelid asymmetry with blinking.

Conclusions: Eyelid asymmetry results from differences in the excitability of motoneurons in the left and right facial motor nuclei and does not appear to involve asymmetries in cortical inputs to the brain stem. Because adaptive processes modify the motoneuron excitability that creates eyelid asymmetry, these processes may underlie changes in blinking associated with facial palsy and may play a role in the development of disorders that affect one side of the face, such as hemifacial spasm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.04-1279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327295PMC
January 2006

Dry eye, blinking, and blepharospasm.

Mov Disord 2002 ;17 Suppl 2:S75-8

Department of Neurobiology & Behavior, SUNY Stony Brook, Stony Brook, New York 11794, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327285PMC
http://dx.doi.org/10.1002/mds.10065DOI Listing
August 2003