Publications by authors named "Joelle Hallak"

32 Publications

AI-automated referral for patients with visual impairment.

Lancet Digit Health 2021 01;3(1):e2-e3

Department of Ophthalmology and Visual Sciences at the University of Illinois at Chicago, Chicago, IL 60612, USA. Electronic address:

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http://dx.doi.org/10.1016/S2589-7500(20)30286-7DOI Listing
January 2021

A Machine Learning Model With Survival Statistics to Identify Predictors of Descemet Stripping Automated Endothelial Keratoplasty Graft Failure.

Authors:
Joelle A Hallak

JAMA Ophthalmol 2021 02;139(2):198-199

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

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http://dx.doi.org/10.1001/jamaophthalmol.2020.5741DOI Listing
February 2021

Prediction of age-related macular degeneration disease using a sequential deep learning approach on longitudinal SD-OCT imaging biomarkers.

Sci Rep 2020 09 22;10(1):15434. Epub 2020 Sep 22.

Department of Biomedical Data Science, Stanford University, Stanford, CA, 94305, USA.

We propose a hybrid sequential prediction model called "Deep Sequence", integrating radiomics-engineered imaging features, demographic, and visual factors, with a recursive neural network (RNN) model in the same platform to predict the risk of exudation within a future time-frame in non-exudative AMD eyes. The proposed model provides scores associated with risk of exudation in the short term (within 3 months) and long term (within 21 months), handling challenges related to variability of OCT scan characteristics and the size of the training cohort. We used a retrospective clinical trial dataset that includes 671 AMD fellow eyes with 13,954 observations before any signs of exudation for training and validation in a tenfold cross validation setting. Deep Sequence achieved high performance for the prediction of exudation within 3 months (0.96 ± 0.02 AUCROC) and within 21 months (0.97 ± 0.02 AUCROC) on cross-validation. Training the proposed model on this clinical trial dataset and testing it on an external real-world clinical dataset showed high performance for the prediction within 3-months (0.82 AUCROC) but a clear decrease in performance for the prediction within 21-months (0.68 AUCROC). While performance differences at longer time intervals may be derived from dataset differences, we believe that the high performance and generalizability achieved in short-term predictions may have a high clinical impact allowing for optimal patient follow-up, adding the possibility of more frequent, detailed screening and tailored treatments for those patients with imminent risk of exudation.
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http://dx.doi.org/10.1038/s41598-020-72359-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508843PMC
September 2020

Development of Screening Criteria for Retinopathy of Prematurity in Ulaanbaatar, Mongolia, Using a Web-based Data Management System.

J Pediatr Ophthalmol Strabismus 2020 Sep;57(5):333-339

Purpose: To describe a process for identifying birth weight (BW) and gestational age (GA) screening guidelines in Mongolia.

Methods: This was a prospective cohort study in a tertiary care hospital in Ulaanbataar, Mongolia, of 193 premature infants with GA of 36 weeks or younger and/or BW of 2,000 g or less) with regression analysis to determine associations between BW and GA and the development of retinopathy of prematurity (ROP).

Results: As BW and GA decreased, the relative risk of developing ROP increased. The relative risk of developing any stage of ROP in infants born at 29 weeks or younger was 2.91 (95% CI: 1.55 to 5.44; P < .001] compared to older infants. The relative risk of developing any type of ROP in infants with BW of less than 1,200 g was 2.41 (95% CI: 1.35 to 4.29; P = .003] and developing type 2 or worse ROP was 2.05 (95% CI: 0.99 to 4.25; P = .05).

Conclusions: Infants in Mongolia with heavier BW and older GA who fall outside of current United States screening guidelines of GA of 30 weeks or younger and/or BW of 1,500 g or less developed clinically relevant ROP. [J Pediatr Ophthalmol Strabismus. 2020;57(5):333-339.].
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http://dx.doi.org/10.3928/01913913-20200804-01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880618PMC
September 2020

The AI Revolution and How to Prepare for It.

Transl Vis Sci Technol 2020 03 18;9(2):16. Epub 2020 Mar 18.

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

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http://dx.doi.org/10.1167/tvst.9.2.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395668PMC
March 2020

Progression of Photoreceptor Degeneration in Geographic Atrophy Secondary to Age-related Macular Degeneration.

JAMA Ophthalmol 2020 10;138(10):1026-1034

Department of Biomedical Data Science, Stanford University, Stanford, California.

Importance: Sensitive outcome measures for disease progression are needed for treatment trials in geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Objective: To quantify photoreceptor degeneration outside regions of GA in eyes with nonexudative AMD, to evaluate its association with future GA progression, and to characterize its spatio-temporal progression.

Design, Setting, And Participants: Monocenter cohort study (Directional Spread in Geographic Atrophy [NCT02051998]) and analysis of data from a normative data study at a tertiary referral center. One hundred fifty-eight eyes of 89 patients with a mean (SD) age of 77.7 (7.1) years, median area of GA of 8.87 mm2 (IQR, 4.09-15.60), and median follow-up of 1.1 years (IQR, 0.52-1.7 years), as well as 93 normal eyes from 93 participants.

Exposures: Longitudinal spectral-domain optical coherence tomography (SD-OCT) volume scans (121 B-scans across 30° × 25°) were segmented with a deep-learning pipeline and standardized in a pointwise manner with age-adjusted normal data (z scores). Outer nuclear layer (ONL), photoreceptor inner segment (IS), and outer segment (OS) thickness were quantified along evenly spaced contour lines surrounding GA lesions. Linear mixed models were applied to assess the association between photoreceptor-related imaging features and GA progression rates and characterize the pattern of photoreceptor degeneration over time.

Main Outcomes And Measures: Association of ONL thinning with follow-up time (after adjusting for age, retinal topography [z score], and distance to the GA boundary).

Results: The study included 158 eyes of 89 patients (51 women and 38 men) with a mean (SD) age of 77.7 (7.1) years. The fully automated B-scan segmentation was accurate (dice coefficient, 0.82; 95% CI, 0.80-0.85; compared with manual markings) and revealed a marked interpatient variability in photoreceptor degeneration. The ellipsoid zone (EZ) loss-to-GA boundary distance and OS thickness were prognostic for future progression rates. Outer nuclear layer and IS thinning over time was significant even when adjusting for age and proximity to the GA boundary (estimates of -0.16 μm/y; 95% CI, -0.30 to -0.02; and -0.17 μm/y; 95% CI, -0.26 to -0.09).

Conclusions And Relevance: Distinct and progressive alterations of photoreceptor laminae (exceeding GA spatially) were detectable and quantifiable. The degree of photoreceptor degeneration outside of regions of retinal pigment epithelium atrophy varied markedly between eyes and was associated with future GA progression. Macula-wide photoreceptor laminae thinning represents a potential candidate end point to monitor treatment effects beyond mere GA lesion size progression.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.2914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426886PMC
October 2020

Artificial intelligence in ophthalmology during COVID-19 and in the post COVID-19 era.

Curr Opin Ophthalmol 2020 Sep;31(5):447-453

Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, Illinois.

Purpose Of Review: To highlight artificial intelligence applications in ophthalmology during the COVID-19 pandemic that can be used to: describe ocular findings and changes correlated with COVID-19; extract information from scholarly articles on SARS-CoV-2 and COVID-19 specific to ophthalmology; and implement efficient patient triage and telemedicine care.

Recent Findings: Ophthalmology has been leading in artificial intelligence and technology applications. With medical imaging analysis, pixel-annotated distinguishable features on COVID-19 patients may help with noninvasive diagnosis and severity outcome predictions. Using natural language processing (NLP) and data integration methods, topic modeling on more than 200 ophthalmology-related articles on COVID-19 can summarize ocular manifestations, viral transmission, treatment strategies, and patient care and practice management. Artificial intelligence for telemedicine applications can address the high demand, prioritize and triage patients, as well as improve at home-monitoring devices and secure data transfers.

Summary: COVID-19 is significantly impacting the way we are delivering healthcare. Given the already successful implementation of artificial intelligence applications and telemedicine in ophthalmology, we expect that these systems will be embraced more as tools for research, education, and patient care.
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http://dx.doi.org/10.1097/ICU.0000000000000685DOI Listing
September 2020

Quantification of Angiogenesis and Lymphangiogenesis in the Dual ex vivo Aortic and Thoracic Duct Assay.

Protein Pept Lett 2020 ;27(1):30-40

Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.

Background: Lymphatic vessel formation (lymphangiogenesis) plays important roles in cancer metastasis, organ rejection, and lymphedema, but the underlying molecular events remain unclear. Furthermore, despite significant overlap in the molecular families involved in angiogenesis and lymphangiogenesis, little is known about the crosstalk between these processes. The ex vivo aortic ring assay and lymphatic ring assay have enabled detailed studies of vessel sprouting, but harvesting and imaging clear thoracic duct samples remain challenging. Here we present a modified ex vivo dual aortic ring and thoracic duct assay using tissues from dual fluorescence reporter Prox1- GFP/Flt1-DsRed (PGFD) mice, which permit simultaneous visualization of blood and lymphatic endothelial cells.

Objective: To characterize the concurrent sprouting of intrinsically fluorescent blood and lymphatic vessels from harvested aorta and thoracic duct samples.

Methods: Dual aorta and thoracic duct specimens were harvested from PGFD mice, grown in six types of endothelial cell growth media (one control, five that each lack a specific growth factor), and visualized by confocal fluorescence microscopy. Linear mixed models were used to compare the extent of vessel growth and sprouting over a 28-day period.

Results: Angiogenesis occurred prior to lymphangiogenesis in our assay. The control medium generally induced superior growth of both vessel types compared with the different modified media formulations. The greatest decrease in lymphangiogenesis was observed in vascular endothelial growth factor-C (VEGF-C)-devoid medium, suggesting the importance of VEGF-C in lymphangiogenesis.

Conclusion: The modified ex vivo dual aortic ring and thoracic duct assay represents a powerful tool for studying angiogenesis and lymphangiogenesis in concert.
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http://dx.doi.org/10.2174/0929866526666190925145842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978644PMC
March 2020

Application of corneal injury models in dual fluorescent reporter transgenic mice to understand the roles of the cornea and limbus in angiogenic and lymphangiogenic privilege.

Sci Rep 2019 08 23;9(1):12331. Epub 2019 Aug 23.

Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.

The role of the corneal epithelium and limbus in corneal avascularity and pathological neovascularization (NV) is not well understood. To investigate the contributions of the corneal and limbal epithelia in angiogenic and lymphangiogenic privilege, we designed five injury models involving debridement of different portions of the cornea and limbus and applied them to the dual-fluorescence reporter Prox1-GFP/Flt1-DsRed mouse, which permits in vivo imaging of blood and lymphatic vessels via fluorescence microscopy. Debridement of the whole cornea resulted in significant hemangiogenesis (HA) and lymphangiogenesis (LA), while that of the whole limbus yielded minimal corneal HA or LA. Following hemilimbal plus whole corneal debridement, corneal NV occurred only through the non-injured aspect of the limbus. Overall, these results suggest that the integrity of the corneal epithelium is important for (lymph)angiogenic privilege, whereas the limbus does not act as a physical or physiologic barrier to invading vessels. In CDh5-CreERT2VEGFR2lox/PGFD mice, conditional deletion of vascular endothelial growth factor receptor 2 in vascular endothelial cells abolished injury-induced HA and LA, demonstrating the utility of this transgenic mouse line for identifying important factors in the process of neovascularization.
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http://dx.doi.org/10.1038/s41598-019-48811-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707148PMC
August 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.
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http://dx.doi.org/10.1016/j.jaapos.2019.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778011PMC
August 2019

An Association Between Large Optic Nerve Cupping and Cognitive Function.

Am J Ophthalmol 2019 10 1;206:40-47. Epub 2019 Jun 1.

Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.

Purpose: To determine if a larger cup-to-disc ratio is associated with poor cognitive function in postmenopausal women without glaucoma or ocular hypertension.

Methods: We used data from the Women's Health Initiative (WHI) hormone trial, originally designed to test effects of hormone therapy (HT) on various health outcomes. Large cup-to-disc ratio was defined as greater than 0.6 in either eye based on stereoscopic optic nerve photographs. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) in the WHI Memory Study. Exclusions were no information on optic nerve grading; no 3MSE scores at the time of the eye examination, ocular hypertension (intraocular pressure >23 mm Hg, Goldmann applanation tonometry), or glaucoma medication use. A generalized linear model for log-transformed 3MSE scores was used for determining the association between large cup-to-disc ratio and 3MSE scores, adjusting for age, race, diabetes, body mass index, cardiovascular disease, smoking, HT randomization, education, and diabetic retinopathy.

Results: Analyses included 1636 women (mean age ± standard deviation, 69.57 ± 3.64 years; 90.39% white). Of those, 122 women had large cup-to-disc ratio. The mean 3MSE scores in women with vs without large cup-to-disc ratio were 95.4 ± 6 vs 96.6 ± 5. In the adjusted model, women with large cup-to-disc ratio had statistically significantly lower 3MSE scores, compared with those without large cup-to-disc ratio, yielding the predicted mean difference in 3MSE scores of 0.75 with a standard error of 0.05 units (P = .04).

Conclusions: Postmenopausal women who had large cup-to-disc ratio without glaucoma or ocular hypertension exhibited lower global cognitive function. Further investigation is warranted. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
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http://dx.doi.org/10.1016/j.ajo.2019.05.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775038PMC
October 2019

Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration: Secondary Analysis of a Randomized Clinical Trial.

JAMA Ophthalmol 2019 07;137(7):738-744

Byers Eye Institute at Stanford, Stanford School of Medicine, Palo Alto, California.

Importance: Risk factors associated with the development of neovascular age-related macular degeneration (AMD) have been identified. However, population size and methods to integrate imaging, genetic, and demographic factors associated with conversion to neovascular AMD are limited, specifically when treatment is administered in 1 eye.

Objective: To determine the imaging, genetic, and demographic factors associated with conversion from nonneovascular to neovascular AMD in fellow eyes.

Design, Setting, And Participants: This post hoc secondary analysis of the 24-month phase 3 multicenter, double-masked, active treatment-controlled HARBOR trial included 686 fellow eyes with nonneovascular AMD at baseline. Imaging features describing the presence, number, extent, density, and relative reflectivity of drusen were automatically extracted from spectral-domain optical coherence tomography scans. Genetic analysis included 34 single-nucleotide polymorphisms. Least absolute shrinkage and selection operator regression was performed to narrow imaging features. Survival analysis and Cox proportional hazards regression were performed to determine the association of the selected imaging features and genetic and demographic factors with conversion to neovascular AMD. Data were collected from November 2016 through October 2017 and analyzed from October 2017 through October 2018.

Exposure: Nonneovascular AMD in the fellow eye.

Main Outcomes And Measures: Features associated with conversion to neovascular AMD. Hazard ratios (HRs) and their 95% CIs were calculated.

Results: Among the 686 fellow eyes included in the analysis (406 [59.2%] women; mean [SD] age, 78.12 [8.28] years), 154 (22.4%) converted to neovascular AMD. Female sex was significantly associated with conversion to neovascular AMD (HR, 1.57; 95% CI, 1.11-2.20; P = .009). After controlling for demographic and treatment effects, drusen area within 3 mm of the fovea (HR, 1.45; 95% CI, 1.24-1.69; HR for 1-SD increase, 1.36 [95% CI, 1.20-1.54]) and mean drusen reflectivity (HR, 3.97; 95% CI, 1.11-14.18; HR for 1-SD increase, 1.32 [95% CI, 1.02-1.71]) were significantly associated with conversion to neovascular AMD. In addition, 1 genetic variant (rs61941274) was found to be associated with conversion to neovascular AMD.

Conclusions And Relevance: Two imaging features (total en face area of drusen restricted to a circular area 3 mm from the fovea and mean drusen reflectivity) and 1 genetic variant (ACAD10 locus) were associated with conversion to neovascular AMD. Drusen characteristics may be associated with conversion to neovascular AMD despite treatment in 1 eye.

Trial Registration: ClinicalTrials.gov identifier: NCT00891735.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.0868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487912PMC
July 2019

Direct and Indirect Flap Measurements in Femtosecond Laser-Assisted In Situ Keratomileusis.

Cornea 2019 Mar;38(3):297-303

Department of Ophthalmology and Visual Sciences, Illinois Eye & Ear Infirmary, University of Illinois at Chicago, Chicago, IL.

Purpose: To compare direct and indirect LASIK flap thickness measurements using ultrasound and Scheimpflug technology.

Methods: Eighty-two eyes treated with laser-assisted in situ keratomileusis refractive surgery using a femtosecond laser (IntraLase FS150) were prospectively included in the study. Flap thickness was set to 115 μm. Corneal flap thickness was measured using the direct method-ie, ultrasound pachymetry immediately after flap construction in the presence of cavitation bubbles-and indirect methods, with subtraction of intraoperative post-lift corneal thickness measured using ultrasound pachymetry (intrastroma) from preoperative central corneal thickness using ultrasound (Indirect-US) or Scheimpflug thinnest pachymetry (Indirect-Scheimpflug).

Results: Mean flap thickness was overestimated using the indirect methods, Indirect-US and Indirect-Scheimpflug (122.6 ± 24.5 μm and 128.1 ± 26.1 μm, respectively; P < 0.0060 and P < 0.0001, respectively). There were no significant correlations between the direct and indirect methods. Indirect-Scheimpflug was significantly higher (P = 0.0122) than Indirect-US. The closest average flap thickness compared with the set parameter of 115 μm was that of the direct method (115.6 ± 8.6 μm; 95% confidence interval: -1.3 to 2.5; P = 0.5163). The direct method provided the lowest SD of all groups (SD: 8.64).

Conclusions: The direct method of flap thickness measurement was the most comparable to the set parameter compared with the indirect subtraction methods. Additional studies are needed to determine which method allows for the most accurate measurement of flap thickness.
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http://dx.doi.org/10.1097/ICO.0000000000001836DOI Listing
March 2019

Five year outcomes of Boston type I keratoprosthesis as primary versus secondary penetrating corneal procedure in a matched case control study.

PLoS One 2018 6;13(2):e0192381. Epub 2018 Feb 6.

Illinois Eye and Ear Infirmary, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, United States of America.

Despite improved retention and reduced complication rates paving the way for the current expansion of applications and surge in prevalence for the Boston type I Keratoprosthesis (KPro), the most frequent indication for its implantation today remains prior graft failure. The purpose of this study is to evaluate the long-term outcomes of primary KPro and compare to secondary implantation in a matched cohort study. This study included patients who underwent KPro implantation in a single center by two surgeons between July 2008 and October 2014. All eyes with KPro implantation as the primary procedure with a minimum follow up of 12 months were matched with eyes with same preoperative diagnoses that underwent secondary KPro implantation. Main outcomes included visual acuity and device retention. A total of 56 eyes were included with 28 eyes in each group. Mean follow up was 5.0 years for both groups. Twenty-nine percent (8) of the eyes in the primary group had a diagnosis of chemical or thermal injuries, 25% (7) aniridia, 18% (5) autoimmune disease, 4% (1) infectious keratitis/neurotrophic cornea, 7% (2) gelatinous corneal dystrophy, 7% (2) ectrodactyly ectodermal dysplasia/limbal stem cell deficiency, and 11% (3) uveitis/hypotony. Sixty-one percent (17) of the eyes in the primary group and 39% (11) in the secondary group maintained a final best-corrected visual acuity of 20/200 or better at a mean follow up of 5.0 years; the probability of maintaining best-corrected vision is 0.83 and 0.49 for primary and secondary groups at 5.0 years (p = 0.02). There is no statistically significant difference between groups in device retention (p = 0.22) or postoperative complication rates (p >0.05). This study demonstrates that Boston KPro implantation may be successful as a primary procedure in patients at high risk of failure with traditional penetrating keratoplasty. The device has a good long-term retention rate and visual outcomes are promising however a larger study is needed for more definitive results.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192381PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800684PMC
April 2018

Retroprosthetic Membrane Formation in Boston Keratoprosthesis: A Case-Control-Matched Comparison of Titanium Versus PMMA Backplate.

Cornea 2018 Feb;37(2):145-150

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

Purpose: Retroprosthetic membrane (RPM) formation is the most common complication after Boston type 1 keratoprosthesis (KPro) implantation. It affects visual acuity and can predispose to corneal melt. Two KPro backplate materials are available: titanium and polymethyl methacrylate (PMMA). This study investigates the influence of the KPro backplate material on visually significant RPM formation.

Methods: A retrospective case-control-matched study involving 40 patients; 20 eyes implanted with a titanium backplate KPro were case-matched with 20 eyes implanted with a PMMA backplate KPro between 2007 and 2015 with 1-year minimum follow-up.

Results: The mean follow-up duration was 28.1 ± 8.9 and 53.6 ± 24.3 months in the titanium and PMMA groups, respectively. At 12 months postoperatively, 7 eyes with titanium and 6 eyes with PMMA backplates developed a visually significant RPM. By the end of the study, a total of 11 eyes with titanium and 9 eyes with PMMA KPros developed a visually significant RPM. There was no statistically significant difference between both groups. Three of 11 eyes with titanium KPros that had a visually significant RPM required surgical membranectomy, whereas all eyes with PMMA KPros were successfully treated with the yttrium-aluminum-garnet laser. Recurrence of RPMs was found in 7/11 eyes in the titanium group and 2/9 eyes in the PMMA group with no statistical significance.

Conclusions: Titanium backplate KPros do not significantly reduce RPM formation compared with PMMA backplate KPros in a case-control-matched setting. A larger prospective study is warranted to evaluate comparative long-term performance and guide newer designs.
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http://dx.doi.org/10.1097/ICO.0000000000001462DOI Listing
February 2018

Depressive Symptoms in Patients With Dry Eye Disease: A Case-Control Study Using the Beck Depression Inventory.

Cornea 2015 Dec;34(12):1545-50

*Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, IL; and †Quantitative Scientific Solutions, LLC, Arlington, Virginia.

Purpose: To measure depressive symptoms in patients with dry eye disease (DED) and controls using the Beck Depression Inventory (BDI) and to determine the association between depressive and DED symptoms.

Methods: Fifty-three patients with DED and 41 controls were recruited to the study. DED symptoms were assessed using the Symptom Burden Tool and Ocular Surface Disease Index tool. Depressive symptoms were assessed using the BDI. Regression diagnostics were performed to detect outliers. Linear statistical models and polynomial regression were used to determine the relationship between depressive symptoms and DED symptoms. An independent t test was performed to determine differences in BDI scores between cases and controls. Scatter plots were generated and linear regression was used to estimate the association between scores. Logistic regression was used for the DED dichotomous outcome and depression status as exposure.

Results: Regression models revealed that the association is linear more than quadratic or cubic. After adjusting for age, sex, race, and psychiatric medication, the regression coefficient between DED symptoms and depressive symptoms among DED cases was 1.22 (95% confidence interval, 0.27-2.18). DED symptom scores and depression scores were statistically significantly different between DED cases and controls. Adjusted logistic regression revealed an odds ratio of 2.79 (95% confidence interval, 0.96-8.12).

Conclusions: This study provides further evidence regarding the association between DED and depression and their symptoms. Prospective studies are needed to understand the mechanisms underlying the association between symptoms of depression and symptoms of DED.
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http://dx.doi.org/10.1097/ICO.0000000000000641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636920PMC
December 2015

Single Nucleotide Polymorphisms in the BDNF, VDR, and DNASE 1 Genes in Dry Eye Disease Patients: A Case-Control Study.

Invest Ophthalmol Vis Sci 2015 Sep;56(10):5990-6

Corneal Neurobiology Laboratory Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, United States.

Purpose: To identify single nucleotide polymorphisms (SNPs) in the brain-derived neurotrophic factor (BDNF), vitamin D receptor (VDR), and DNASE1 genes that may be associated with dry eye disease (DED), and determine whether this association varies by the presence of depression.

Methods: A case-control study was performed with 64 DED cases and 51 controls. We collected 2 mL of saliva following a routine eye exam. Genotyping was performed using both custom and predesigned TaqMan SNP genotyping assays for 12 hypothesized SNPs. Genotype and allele frequencies of cases and controls were evaluated. Odds ratios were calculated for allele frequencies. Stratified analysis was performed to determine if the association between SNPs and DED varied by depression status.

Results: A total of 18% of cases had the minor allele A of Val66Met (rs6265) SNP in the BDNF gene compared with 9% of the controls (P = 0.05). Odds ratio was 2.22. Two SNPs (Fokl-rs2228570 and Apal-rs7975232) in the VDR genes also varied between DED cases and controls. Cases were 1.72 and 1.66 times more likely to have the minor allele A in rs2228570 and rs7975232, respectively, than controls (P = 0.06 for both). While not statistically significant, among patients with depression, DED cases were 3.93 times more likely to have the minor allele A of the Val66Met SNP compared to controls.

Conclusions: This pilot study showed that Val66Met in the BDNF gene and two SNPs, Fokl and Apal, in the VDR gene may potentially be associated with DED. Additionally, the association between DED and Val66Met may vary by depression status.
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http://dx.doi.org/10.1167/iovs.15-17036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102496PMC
September 2015

Vision-related quality-of-life assessment using NEI VFQ-25 in patients after Boston keratoprosthesis implantation.

Cornea 2015 Feb;34(2):160-4

*Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, IL; and †Quantitative Scientific Solutions, LLC, Washington, DC.

Purpose: The aim of this study was to determine the impact of Boston keratoprosthesis (KPro) implantation on patient-reported visual function using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25).

Methods: This is a prospective study of patients undergoing implantation of Boston KPro. The NEI VFQ-25 was used to assess vision-related quality of life preoperatively and postoperatively at 3 and 6 months and yearly thereafter. Baseline scores were compared with postoperative scores using paired t test. Stratified analysis was performed to compare results by visual acuity of the contralateral eye.

Results: Twenty-four patients were included. Mean baseline NEI VFQ-25 overall score was 44.6. At the first follow-up time point, mean overall score was 70.0, representing a statistically significant change from baseline (P < 0.001). Breakdown of subcategories within VFQ-25 showed significant improvement in general vision, near and distance activities, social functioning, mental health, role difficulties, dependency, color vision, and peripheral vision (P < 0.05). This improvement was also observed when comparing baseline scores with postoperative scores at average follow-up of 16 months. Although a greater change in scores was observed in patients who had poor vision in the contralateral eye, patients with vision better than 20/200 in the nonsurgical eye showed statistically significant improvement in overall scores and subscale scores compared with baseline.

Conclusions: The quality of life of patients who underwent KPro significantly improved postoperatively compared with their preoperative status. These results did not change when stratifying by visual acuity of the contralateral eye.
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http://dx.doi.org/10.1097/ICO.0000000000000310DOI Listing
February 2015

Cyclotorsional and non-cyclotorsional components of eye rotation observed from sitting to supine position.

Br J Ophthalmol 2015 Jan 12;99(1):49-53. Epub 2014 Aug 12.

Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago-UIC, USA Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of Sao Paulo-UNIFESP, Brazil.

Purpose: Evaluate average cyclotorsional and non-cyclotorsional components (NCY) of eye rotation from sitting to supine, and associate average cyclotorsion to different variables.

Methods: Medical records of patients who underwent bilateral sequential laser refractive surgery were retrospectively evaluated. Recorded variables included the patient's age, refraction, automated keratometry, pupil displacement and eye rotation from sitting to supine position. Measured iris rotation (total rotation, TR) was decomposed into two components: NCY, defined as the common rotation component of each eye of the same patient, and cyclotorsional component (CY), defined as the assumed independent eye rotation for each eye in relation to the face, so that TR=NCY+CY. Cyclotorsion ratio (CR) was calculated as CR=|CY|/|TR|, and used to correlate CY with TR for each eye.

Results: Data from 310 eyes of 155 patients were evaluated. TR was +1.43° ±3.41° (-8.30° to +9.20°). Average CYs and NCYs per patient were +1.43°±2.04° (-3.15± to +7.40°) and -0.28°±2.72° (-6.85° to +7.15°), respectively. TR demonstrated that 40.6% and 8.4% of patients presented bilateral excyclotorsion and incyclotorsion, respectively. When excluding NCYs, average CYs demonstrated that 74.2% of patients presented excyclotorsion and 23.9% presented incyclotorsion. CR demonstrated that TR represented from 75% to 125% of average CY in 19.68% of the eyes. TR overestimated and underestimated average CYs above these limits in 52.26% and 28.06% of the eyes, respectively. There was no statistical association between average CYs and the different variables.

Discussion: This study demonstrates that most of the rotations previously attributed to torsional components were probably due to NCYs, such as postural misalignments. Apparently, the amplitude of cyclotorsional movements is smaller than observed in previous reports, and could not be associated with any studied variable.
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http://dx.doi.org/10.1136/bjophthalmol-2014-304975DOI Listing
January 2015

Symptom burden of patients with dry eye disease: a four domain analysis.

PLoS One 2013 13;8(12):e82805. Epub 2013 Dec 13.

Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, United States of America.

Purpose: To determine which sensory (symptom persistence and intensity) and reactive (activity and affective interference) domains of symptom analysis are essential for assessing symptom burden in dry eye disease (DED) patients.

Methods: A symptom domain tool was developed to investigate all four symptom domains in DED. In a cross-sectional pilot study, we administered the symptom burden tool and the Ocular Surface Disease Index (OSDI) questionnaire to 48 DED patients. Total and domain scores from the symptom burden tool and the OSDI were normalized to achieve comparability. Spearman correlation coefficients were calculated to measure the relationship between domains and subscales. Agreement between the symptom burden tool and OSDI was assessed by Bland-Altman plot. Assigned treatments were compared by symptom burden to determine whether treatment aggressiveness is linked to symptom intensity.

Results: There was high agreement between the symptom burden tool and the OSDI. Symptom persistence had a stronger correlation with affective interference (r  =  0.62 for the symptom burden tool and r = 0.73 for the OSDI) than activity interference (r = 0.58 for the symptom burden tool and r = 0.60 for the OSDI). Symptom intensity correlated weakly with affective interference (r = 0.38) and activity interference (r = 0.37) in the symptom burden tool (OSDI does not have a subscale for intensity). In patients with equal persistence of symptoms, those having high symptom intensity were receiving more aggressive treatment (66.7%) than those with lower symptom intensity (33.3%).

Conclusions: Persistence of symptoms correlates better with affective interference than activity interference. Intensity of symptoms may be important for treatment decisions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082805PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862676PMC
October 2014

Tear fluid extracellular DNA: diagnostic and therapeutic implications in dry eye disease.

Invest Ophthalmol Vis Sci 2013 Dec 11;54(13):8051-61. Epub 2013 Dec 11.

Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois.

Purpose: To determine the abundance of extracellular DNA (eDNA) in tear fluid of patients with dry eye disease (DED) and to report clinical outcomes after DNase I eyedrops use to reduce excessive tear fluid eDNA.

Methods: Tear fluid was collected from healthy control subjects and patients with DED. The eDNA abundance was determined with the PicoGreen dye assay. The DED symptoms and clinical signs were recorded and correlated with eDNA abundance. Two patients with DED having excessive eDNA in tear fluid were treated with DNase I eyedrops.

Results: The PicoGreen dye assay measures tear fluid eDNA abundance after a 2-minute incubation time. With longer incubations, admixed cells also contribute to eDNA measurements. The mean (SE) eDNA abundance in healthy control subjects' tear fluid was 1.4 (0.2) μg/mL. The mean (SE) eDNA abundance in tear fluid of patients with nonautoimmune DED, autoimmune DED, and graft versus host disease was significantly higher: the values were 2.9 (0.6), 5.2 (1.2), and 9.1 (2.3) μg/mL, respectively (P < 0.05). In most of these patients, the PicoGreen dye kinetic assay of tear fluid showed an increase in fluorescence signal due to the presence of viable cells in tear fluid. Tear fluid eDNA had the best correlation with corneal Rose Bengal staining (r = 0.55). Treatment of patients having DED with DNase I eyedrops reduced eDNA abundance, abrogated signal increase, and improved comfort.

Conclusions: Excessive eDNA is present in tear fluid of patients with dry eyes. A novel therapeutic approach for managing DED may be to measure eDNA abundance in tear fluid with the PicoGreen dye assay and reduce excessive amounts with DNase I eyedrops.
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http://dx.doi.org/10.1167/iovs.13-12844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860379PMC
December 2013

CD11b+GR1+ myeloid cells secrete NGF and promote trigeminal ganglion neurite growth: implications for corneal nerve regeneration.

Invest Ophthalmol Vis Sci 2013 Sep 3;54(9):5920-36. Epub 2013 Sep 3.

Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA.

Purpose: We characterized fluorescent bone marrow cells (YFP(+) BMCs) in the thy1-YFP mouse and determine if they promote trigeminal ganglion (TG) cell neurite growth.

Methods: Excimer laser annular keratectomy was performed in thy1-YFP mice, and corneas were imaged. BMCs were harvested from femur and tibia, and the expression of surface markers on YFP(+) BMCs was analyzed by flow cytometry. The immunosuppressive action of BMCs (YFP(+) and YFP(-)) was evaluated in an allogenic mixed lymphocyte reaction (MLR). Neurotrophic action of BMCs (YFP(+) and YFP(-)) was determined in compartmental and transwell cultures of dissociated TG cells.

Results: Following annular keratectomy, YFP(+) BMCs infiltrated the cornea. YFP(+) BMCs shared surface markers (CD11b+Gr1+Ly6C+Ly6G-F4/80(low)) with monocytic myeloid-derived suppressor cells (MDSCs), had similar morphology, and suppressed T-cell proliferation in allogenic MLR in a dose-dependent manner. YFP(+) BMCs, but not YFP(-) BMCs, significantly increased growth of TG neurites in vitro. When cultured in a transwell with TG neurites, YFP(+) BMCs expressed neurotrophins and secreted nerve growth factor (NGF) in conditioned medium. YFP(+) BMCs that infiltrated the cornea maintained their phenotype and actions (neuronal and immune).

Conclusions: YFP(+) BMCs in thy1-YFP mice have immunophenotypic features of MDSCs. They secrete NGF and promote neuroregeneration. Their immunosuppressive and neurotrophic actions are preserved after corneal infiltration. These findings increase our understanding of the beneficial roles played by leukocyte trafficking in the cornea and may lead to therapeutic strategies that use NGF-secreting myeloid cells to repair diseased or injured neurons.
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http://dx.doi.org/10.1167/iovs.13-12237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762328PMC
September 2013

Correlation between corneal and scleral pneumatonometry: an alternative method for intraocular pressure measurement.

Am J Ophthalmol 2013 Nov 12;156(5):902-906.e1. Epub 2013 Aug 12.

Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Department of Ophthalmology and Visual Sciences, Chicago, Illinois.

Purpose: To evaluate scleral pneumatonometry as an alternative method for measuring intraocular pressure (IOP).

Design: Prospective cross-sectional study.

Methods: Adult subjects with healthy eyes were recruited from the Comprehensive Eye Service at the University of Illinois Eye and Ear Infirmary from August 2008 through February 2009. Study measurements included corneal pneumatonometry (IOPk), scleral pneumatonometry (IOPs), axial length (AL), spherical equivalent (SE), and central corneal thickness (CCT). Main outcome measures were scleral IOP and corneal IOP.

Results: Analysis included a monocular data set from single eyes of 97 subjects (age: 18-82 years). IOPs was consistently higher than IOPk, and correlated positively with IOPk (r = 0.57, P < .0001), age (r = 0.51, P < .0001), and SE (r = 0.32, P = .0002). The difference between scleral and corneal IOP (IOPs - IOPk) correlated positively with IOPs (r = 0.89, P < .0001), age (r = 0.57, P < .0001), and SE (r = 0.34, P < 0.0001). Bland-Altman analysis for agreement between scleral and corneal pneumatonometry measurements showed a mean difference of 8.08 mm Hg, with the 95% limit of agreement between -3.47 and 19.64 mm Hg. Regression analysis yielded the following equation: IOPk = 11.9 + 0.32(IOPs) - 0.05(Age).

Conclusions: Scleral pneumatonometry correlates positively with corneal pneumatonometry and is more accurate at lower values and in younger patients. When adjusted for age, scleral pneumatonometry may be an adequate alternative in situations where corneal measurements are impractical.
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http://dx.doi.org/10.1016/j.ajo.2013.05.045DOI Listing
November 2013

Peripapillary retinal nerve fiber layer thickness in sickle-cell hemoglobinopathies using spectral-domain optical coherence tomography.

Am J Ophthalmol 2013 Mar 4;155(3):456-464.e2. Epub 2012 Dec 4.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.

Purpose: To determine whether patients with a sickle-cell hemoglobinopathy without glaucoma have peripapillary retinal nerve fiber layer (RNFL) thinning by spectral-domain optical coherence tomography.

Design: Prospective study.

Methods: All patients with a sickle cell hemoglobinopathy (sickle-cell disease, sickle-cell hemoglobin C disease, and sickle-cell thalassemia) and age-similar, race-matched controls underwent a comprehensive eye examination and spectral-domain optical coherence tomography of the macula and optic nerve head using the Heidelberg Spectralis (Heidelberg Engineering, Inc, Carlsbad, California, USA). Participants with prior retinal treatments (laser or surgery), diabetes mellitus, glaucoma, or other ocular diseases were excluded. The sickle-cell disease patients were grouped into those with focal macular thinning and those without. Those with macular thinning were grouped further into mild, moderate, and severe thinning groups based on temporal macular thickness. Analysis of variance testing and post hoc analysis with the Tukey test and Pearson correlation were performed to assess for peripapillary RNFL thickness differences among different groups.

Results: One hundred fifty-one eyes of 88 sickle-cell patients and 55 eyes of 30 age-similar and race-matched (black) controls were included. Sickle-cell patient eyes with macular thinning (n = 81) had thinner mean peripapillary RNFL thicknesses in the nasal sector (P = .01) compared with non-sickle-cell control eyes and in the superotemporal sector (P = .01) compared with sickle-cell patient eyes without macular thinning (n = 70). In the severe macular thinning subgroup (n = 55), the mean peripapillary RNFL thickness was significantly thinner than that of controls (P < .05) in 6 of 7 sectors. There is a positive linear relationship between temporal macular thickness and global peripapillary RNFL thickness with a Pearson correlation coefficient of 0.60 (P < .0001).

Conclusions: Nonglaucomatous, black sickle-cell patients with focal macular thinning on spectral-domain optical coherence tomography have significantly thinner peripapillary RNFL than those without macular thinning or controls. The degree of thinning correlates with severity of temporal macular thinning. These patients may require different peripapillary RNFL thickness thresholds for future glaucoma evaluations.
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http://dx.doi.org/10.1016/j.ajo.2012.09.015DOI Listing
March 2013

Ocular surface extracellular DNA and nuclease activity imbalance: a new paradigm for inflammation in dry eye disease.

Invest Ophthalmol Vis Sci 2012 Dec 17;53(13):8253-63. Epub 2012 Dec 17.

Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois 60612, USA.

Purpose: We determined whether nucleases are deficient in the tear fluid of dry eye disease (DED) patients, and whether this causes extracellular DNA (eDNA) and neutrophil extracellular trap (NET) accumulation in the precorneal tear film, thus causing ocular surface inflammation.

Methods: Exfoliated cells adhered to Schirmer test strips were collected on glass slides, and immunofluorescence confocal microscopy was used to evaluate neutrophils, eDNA, NETs, and their molecular components. Similar experiments were performed with mucoid films collected from the inferior conjunctival fornix or bulbar conjunctiva. We used quantitative PCR to evaluate eDNA signaling pathways and inflammatory cytokine expression. We also determined the amount of ocular surface eDNA and evaluated tear fluid nuclease activity.

Results: eDNA, NETs, and neutrophils were present on the ocular surface in DED patients and abundant in mucoid films. NETs consisted of eDNA, histones, cathelicidin, and neutrophil elastase. Tear fluid nuclease activity was decreased significantly in DED patients, whereas the amount of eDNA on the ocular surface was increased significantly. Expression of genes downstream of eDNA signaling, such as TLR9, MyD88, and type I interferon, as well as the inflammatory cytokines interleukin-6 and tumor necrosis factor-α, was significantly increased in DED patients.

Conclusions: Extracellular DNA production and clearance mechanisms are dysregulated in DED. Nuclease deficiency in tear fluid allows eDNA and NETs to accumulate in precorneal tear film, and results in ocular surface inflammation. These findings point to novel therapeutic interventions in severe DED based on clearance of eDNA, NETs, and other molecular components from the ocular surface.
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http://dx.doi.org/10.1167/iovs.12-10430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525138PMC
December 2012

Semaphorin 7a links nerve regeneration and inflammation in the cornea.

Invest Ophthalmol Vis Sci 2012 Jul 9;53(8):4575-85. Epub 2012 Jul 9.

Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, 60612, USA.

Purpose: We determined Semaphorin 7a (Sema7a) localization and abundance in naive corneas and in corneas after nerve-transecting lamellar flap surgery, and determined the effect of Sema7a supplementation on corneal nerve regeneration and inflammation.

Methods: Immunolocalization and Western blot analyses were performed to evaluate the abundance of Sema7a in naive corneas and corneas undergoing nerve regeneration after lamellar corneal surgery in thy1-YFP+ neurofluorescent mice. We used compartmental cultures of dissociated trigeminal ganglion cells to determine the effect of Sema7a exposure on neurite outgrowth in vitro. Finally, a Sema7a pellet was implanted under the corneal flap after lamellar transection surgery to determine the neuronal and inflammatory effects of Sema7a supplementation in vivo.

Results: Sema7a was expressed in the corneal epithelium and stromal keratocytes, but was more abundant in the epithelium (74.3%) compared to the stroma (25.7%, P = 0.02). Sema7a expression was increased significantly in the cornea after lamellar corneal surgery and was localized to stromal cells near the regenerating nerve fronds. Exposure of trigeminal neurites to Sema7a (20 nM) in the side compartment increased neurite length significantly. The implanted Sema7a pellet increased significantly YFP+ inflammatory cell influx into the cornea as well as increased corneal nerve length.

Conclusions: Sema7a is expressed constitutively in the cornea, and potently stimulates nerve regeneration and inflammatory cell influx. Therefore, this immune semaphorin links nerve regeneration and inflammatory processes in the cornea.
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http://dx.doi.org/10.1167/iovs.12-9760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394693PMC
July 2012

Corneal neurotoxicity due to topical benzalkonium chloride.

Invest Ophthalmol Vis Sci 2012 Apr 6;53(4):1792-802. Epub 2012 Apr 6.

Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA.

Purpose: The aim of this study was to determine and characterize the effect of topical application of benzalkonium chloride (BAK) on corneal nerves in vivo and in vitro.

Methods: Thy1-YFP+ neurofluorescent mouse eyes were treated topically with vehicle or BAK (0.01% or 0.1%). Wide-field stereofluorescence microscopy was performed to sequentially image the treated corneas in vivo every week for 4 weeks, and changes in stromal nerve fiber density (NFD) and aqueous tear production were determined. Whole-mount immunofluorescence staining of corneas was performed with antibodies to axonopathy marker SMI-32. Western immunoblot analyses were performed on trigeminal ganglion and corneal lysates to determine abundance of proteins associated with neurotoxicity and regeneration. Compartmental culture of trigeminal ganglion neurons was performed in Campenot devices to determine whether BAK affects neurite outgrowth.

Results: BAK-treated corneas exhibited significantly reduced NFD and aqueous tear production, and increased inflammatory cell infiltration and fluorescein staining at 1 week (P < 0.05). These changes were most significant after 0.1% BAK treatment. The extent of inflammatory cell infiltration in the cornea showed a significant negative correlation with NFD. Sequential in vivo imaging of corneas showed two forms of BAK-induced neurotoxicity: reversible neurotoxicity characterized by axonopathy and recovery, and irreversible neurotoxicity characterized by nerve degeneration and regeneration. Increased abundance of beta III tubulin in corneal lysates confirmed regeneration. A dose-related significant reduction in neurites occurred after BAK addition to compartmental cultures of dissociated trigeminal ganglion cells. Although both BAK doses (0.0001% and 0.001%) reduced nerve fiber length, the reduction was significantly more with the higher dose (P < 0.001).

Conclusion: Topical application of BAK to the eye causes corneal neurotoxicity, inflammation, and reduced aqueous tear production.
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http://dx.doi.org/10.1167/iovs.11-8775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995561PMC
April 2012

Risk factors associated with incident cataracts and cataract surgery in the Age-related Eye Disease Study (AREDS): AREDS report number 32.

Ophthalmology 2011 Nov;118(11):2113-9

Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute/National Institutes of Health, Bethesda, Maryland, USA.

Objective: To investigate potential risk factors associated with incident nuclear, cortical, and posterior subcapsular (PSC) cataracts and cataract surgery in participants in the Age-Related Eye Disease Study (AREDS).

Design: Clinic-based prospective cohort study.

Participants: Persons (n = 4425) 55 to 80 years of age enrolled in a controlled clinical trial of antioxidant vitamins and minerals, AREDS, for age-related macular degeneration and cataract.

Methods: Lens photographs were graded centrally for nuclear, cortical, and PSC opacities using the AREDS system for classifying cataracts. Type-specific incident cataracts were defined as an increase in cataract grade from none or mild at baseline to a grade of moderate at follow-up, also with a grade of at least moderate at the final visit, or cataract surgery. Cox regression analyses were used to assess baseline risk factors associated with type-specific opacities and cataract surgery.

Main Outcome Measures: Moderate cataract was defined as a grade of 4.0 or more for nuclear opacity, 10% or more involvement within the full visible lens for cortical opacity, and 5% or more involvement of the central 5-mm circle of the lens for PSC opacity. These were graded on baseline and annual lens photographs.

Results: A clinic-based cohort of 4425 persons 55 to 80 years of age at baseline was followed up for an average of 9.8±2.4 years. The following associations were found: increasing age with increased risk of all types of cataract and cataract surgery; males with increased risk of PSC and decreased risk of cortical cataracts; nonwhite persons with increased risk of cortical cataract; hyperopia with decreased risk of PSC, nuclear cataract, and cataract surgery; Centrum (Wyeth Consumer Healthcare, Madison, NJ) use with decreased risk of nuclear cataract; diabetes with increased risk of cortical, PSC cataract, and cataract surgery; higher educational level with decreased risk of cortical cataract; and smoking with increased risk of cortical cataract and cataract surgery. Estrogen replacement therapy in female participants increased the risk of cataract surgery.

Conclusions: These findings largely are consistent with the results of previous studies, providing further evidence for possible modifiable risk factors for age-related cataract.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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http://dx.doi.org/10.1016/j.ophtha.2011.03.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178670PMC
November 2011

Novel aspects of corneal angiogenic and lymphangiogenic privilege.

Prog Retin Eye Res 2010 May 25;29(3):208-48. Epub 2010 Jan 25.

Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, 1855W. Taylor Street, Chicago, IL, USA.

In this article, we provide the results of experimental studies demonstrating that corneal avascularity is an active process involving the production of anti-angiogenic factors, which counterbalance the pro-angiogenic/lymphangiogenic factors that are upregulated during wound healing. We also summarize pertinent published reports regarding corneal neovascularization (NV), corneal lymphangiogenesis and corneal angiogenic/lymphangiogenic privilege. We outline the clinical causes of corneal NV, and discuss the angiogenic proteins (VEGF and bFGF) and angiogenesis regulatory proteins. We also describe the role of matrix metalloproteinases MMP-2, -7, and MT1-MMP, anti-angiogenic factors, and lymphangiogenic regulatory proteins during corneal wound healing. Established and potential new therapies for the treatment of corneal neovascularization are also discussed.
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http://dx.doi.org/10.1016/j.preteyeres.2010.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685179PMC
May 2010

Thin-flap (sub-Bowman keratomileusis) versus thick-flap laser in situ keratomileusis for moderate to high myopia: case-control analysis.

J Cataract Refract Surg 2008 Dec;34(12):2073-8

Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois 60612, USA.

Purpose: To compare the refractive and visual outcomes of sub-Bowman keratomileusis (SBK) and thick-flap laser in situ keratomileusis (LASIK) for moderate to high myopia and evaluate the effect of corneal flap thickness on outcomes.

Setting: Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.

Methods: Two studies were performed. In the first study, the refractive and visual outcomes in 33 eyes that had SBK (flap thickness 82 to 120 microm) and 62 eyes that had thick-flap LASIK (flap thickness >or=160) were retrospectively analyzed. Inclusion criteria were spherical equivalent -4.0 to -10.0 diopters (D), astigmatism 3.0 D or less, and follow-up 3 months or more. In the second study, the influence of flap thickness was evaluated. A case-control matched study (21 pairs) that controlled for residual stromal bed (RSB) thickness was performed.

Results: The mean flap thickness was 110.2 microm+/-9.2 (SD) in the SBK group and 179.2+/-19.5 microm in the thick-flap LASIK group. There were no significant differences in visual outcomes. In the second study with equivalent RSB thickness, case-control matched comparisons between SBK (mean 108.6+/-8.0 microm) and thick-flap LASIK (mean 165.7+/-12.6 microm) showed no differences in preoperative and postoperative refractive and visual outcomes. Comparison of the intended versus achieved correction showed no significant differences between the 2 groups.

Conclusion: Retrospective analyses showed that the safety, efficacy, and predictability of SBK were similar to those of conventional thick-flap LASIK in corneas with equivalent RSB thickness.
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http://dx.doi.org/10.1016/j.jcrs.2008.08.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763554PMC
December 2008