Publications by authors named "Allen O Eghrari"

50 Publications

Efficacy and Safety Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease: 12-Month Results From the PREVAIL VII Study.

Transl Vis Sci Technol 2021 Jan 25;10(1):32. Epub 2021 Jan 25.

National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Purpose: In survivors of Ebola virus disease (EVD), intraocular viral persistence raises questions about the timing and safety of cataract surgery. To the best of our knowledge, this is the first controlled study evaluating Ebola virus persistence and cataract surgery safety and outcomes in EVD survivors.

Methods: Seropositive EVD survivors and seronegative controls with vision worse than 20/40 from cataract and without active intraocular inflammation were enrolled. Aqueous humor from survivors was tested with reverse transcription-polymerase chain reaction for Ebola viral RNA. Participants underwent manual small-incision cataract surgery and 1 year of follow-up examinations.

Results: Twenty-two eyes of 22 survivors and 12 eyes of eight controls underwent cataract surgery. All of the aqueous samples tested negative for Ebola viral RNA. Median visual acuity improved from 20/200 at baseline to 20/25 at 1 year in survivors and from count fingers to 20/50 in controls (overall, < 0.001; between groups, = 0.07). After a 1-month course of topical corticosteroids, 55% of survivors and 67% of controls demonstrated at least 1+ anterior chamber cell. Twelve months after surgery, optical coherence tomography revealed a median increase in macular central subfield thickness of 42 µm compared with baseline (overall, = 0.029; between groups, = 0.995).

Conclusions: EVD survivors and controls demonstrated significant visual improvement from cataract surgery. The persistence of intraocular inflammation highlights the importance of follow-up. The absence of detectable intraocular Ebola viral RNA provides guidance regarding the safety of eye surgery in Ebola survivors.

Translational Relevance: These findings demonstrate the safety and efficacy of cataract surgery in Ebola survivors and will inform ocular surgery guidelines in this population.
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http://dx.doi.org/10.1167/tvst.10.1.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838547PMC
January 2021

Techniques, Outcomes, and Complications of Preloaded, Trifolded Descemet Membrane Endothelial Keratoplasty Using the DMEK EndoGlide.

Cornea 2021 Jan 18. Epub 2021 Jan 18.

Division of Cornea, Cataract and External Diseases, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD University of Maryland at College Park, College Park, MD.

Purpose: To describe 2 insertion techniques, outcomes, and complications of preloaded, trifolded Descemet membrane endothelial keratoplasty (DMEK) cases using the DMEK EndoGlide inserter.

Methods: This retrospective, consecutive case series analyzed the first 35 cases using the DMEK EndoGlide performed between October 2018 and October 2019 at a single center. Preloaded, trifolded DMEK tissues were delivered through a fluid-injected or pull-through technique. To inject the tissue, a burst of fluid was delivered into the lumen of the injector with a second instrument. Postoperatively, best-spectacle corrected visual acuity (BSCVA), pachymetry, graft survival, and complications were assessed.

Results: Thirty-five eyes of 29 patients underwent DMEK alone (n = 11), with cataract surgery (n = 21), or with additional surgeries (n = 3). Of these, 19 (54.3%) grafts were injected. Video analysis revealed a median time of 3.5 minutes from graft insertion to opening for gas insertion. Median preoperative BSCVA of 0.398 logMAR improved to 0.097 logMAR (P = 0.02) at 9 months. Median pachymetry decreased from 619 μm to 551 μm (P = 0.03) at 9 months. Median donor endothelial cell count of 2890.5 cells/mm2 reduced to 2123 cells/mm2 (26.6% endothelial cell loss; P = 0.008) 6 months postoperatively. One (2.9%) graft failed due to inverted marking at the eye bank and subsequent reverse implantation.

Conclusions: Pre-loaded, tri-folded tissues can be implanted with acceptable levels of endothelial cell loss. We describe a no-touch method of injecting pre-loaded, tri-folded tissue and highlight incorrect marking as a potential complication. This may not be identifiable intraoperatively due to lack of scroll formation.
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http://dx.doi.org/10.1097/ICO.0000000000002648DOI Listing
January 2021

Characterization of Ebola Virus-Associated Eye Disease.

JAMA Netw Open 2021 Jan 4;4(1):e2032216. Epub 2021 Jan 4.

National Public Health Institute of Liberia, Monrovia, Liberia.

Importance: Survivors of Ebola virus disease (EVD) may experience ocular sequelae. Comparison with antibody-negative individuals from the local population is required to characterize the disease.

Objective: To assess features of ophthalmic disease specific to EVD.

Design, Setting, And Participants: This baseline cross-sectional analysis of survivors of EVD and their close contacts was conducted within PREVAIL III, a 5-year, longitudinal cohort study. Participants who enrolled at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 were included in this analysis. Close contacts were defined as household members or sex partners of survivors of EVD. Data were analyzed from July 2016 to July 2020.

Exposures: All participants, both survivors and close contacts, underwent testing of IgG antibody levels against Ebola virus surface glycoprotein.

Main Outcomes And Measures: Ocular symptoms, anterior and posterior ophthalmologic examination findings, and optical coherence tomography images were compared between antibody-positive survivors and antibody-negative close contacts.

Results: A total of 564 antibody-positive survivors (320 [56.7%] female; mean [SD] age, 30.3 [14.0] years) and 635 antibody-negative close contacts (347 [54.6%] female; mean [SD] age, 25.8 [15.5] years) were enrolled in this study. Survivors were more likely to demonstrate color vision deficit (28.9% vs 19.0%, odds ratio [OR], 1.6; 95% CI, 1.2-2.1) and lower intraocular pressure (12.4 vs 13.5 mm Hg; mean difference, -1.2 mm Hg; 95% CI, -1.6 to -0.8 mm Hg) compared with close contacts. Dilated fundus examination revealed a higher percentage of vitreous cells (7.8% vs 0.5%; OR, 16.6; 95% CI, 5.0-55.2) and macular scars (4.6% vs 1.6%; OR, 2.8; 95% CI, 1.4-5.5) in survivors than in close contacts. Uveitis was present in 26.4% of survivors and 12.1% of close contacts (OR, 2.4; 95% CI, 1.8-3.2). Among all participants with uveitis, survivors were more likely than close contacts to have intermediate uveitis (34.2% vs 6.5% of all cases; OR, 7.8; 95% CI, 3.1-19.7) and had thicker mean central subfield thickness on optical coherence tomography (222 vs 212 μm; mean difference, 14.4 μm; 95% CI, 1.9-26.9 μm).

Conclusions And Relevance: In this cross-sectional study, survivors of EVD had a distinct spectrum of ocular and neuro-ophthalmologic findings compared with close contacts that potentially require medical and surgical treatment.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.32216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786253PMC
January 2021

Peripheral-to-central ratio of Guttae: validity and reliability of an objective method to characterize severity of Fuchs endothelial corneal dystrophy.

Graefes Arch Clin Exp Ophthalmol 2021 Mar 31;259(3):685-690. Epub 2020 Oct 31.

Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Purpose: Common methods of measuring severity of Fuchs endothelial corneal dystrophy (FECD) are limited in objectivity, reliability, or start with a variable baseline that prevents distinguishing healthy from affected eyes. The aim of this study was to describe a method of grading FECD that overcomes these limitations.

Methods: Fifteen patients with Fuchs endothelial corneal dystrophy were included in the study. Guttae were imaged with a slit lamp beam 8 mm tall; the bottom 4 mm half of each image was divided into two equally-sized sections. Guttae were counted by four independent graders blinded to disease severity scores. The peripheral:central guttae ratio was compared to modified Krachmer clinical severity scores. The peripheral:central guttae ratio was compared between mild (severity 0.5-3) versus moderate-to-severe (severity 4-5) disease. Receiver operating characteristics defined optimal ratio cutoffs for mild versus moderate-to-severe disease.

Results: Increased peripheral guttae and peripheral:central guttae ratio correlated with Krachmer severity (p = 0.021 and p = 0.009, respectively). The difference between mild and moderate-to-severe cases for the peripheral:central guttae ratio was significant (p < 0.001). Inter-rater reliability of total guttae count was high (coefficient = 0.82, p < 0.001). A peripheral:central guttae ratio of 0.16 was the ideal cut-off point (area under the curve = 0.79, sensitivity = 0.78, and specificity = 0.80).

Conclusion: In this pilot study, the peripheral:central ratio of guttae correlates with subjective clinical severity of Fuchs dystrophy. It starts at a common baseline, has good inter-rater reliability, does not require dilation, and can be conducted with a smartphone and slit-lamp.
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http://dx.doi.org/10.1007/s00417-020-04985-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904627PMC
March 2021

Corneal thinning and cornea guttata in patients with mutations in TGFB2.

Can J Ophthalmol 2020 08 16;55(4):336-341. Epub 2020 Apr 16.

National Institute of Allergy and Infectious Diseases, Bethesda, MD.

Objective: Human genome-wide association studies and animal models suggest a role for TGFB2 in contributing to the corneal thickness phenotype. No specific mutations, however, have been reported in this gene that affect corneal thickness. We sought to determine if haploinsufficiency of TGFB2 in humans associated with Loeys-Dietz syndrome type 4 is associated with corneal thinning.

Design: Observational cohort study of families with Loeys-Dietz syndrome type 4, caused specifically by TGFB2 mutations, in a tertiary care setting.

Participants: Three probands with pathogenic mutations in TGFB2 and family members underwent comprehensive ophthalmic examination.

Methods: Clinical assessment included Scheimpflug imaging, specular microscopy, and slit-lamp biomicroscopy. We measured visual acuity, axial length, refractive error, and central corneal thickness.

Results: Clinical evaluation of 2 probands identified corneal thinning and cornea guttata, despite a young age and distinct mutations in TGFB2 (c.905G>A, p.Arg302His; c.988C>A, p.Arg330Ser). In the third family, corneal thinning co-segregated with a TGFB2 mutation (c.1103G>A, p.Gly368Glu), although without apparent guttae.

Conclusions: In this series, participants with TGFB2 mutations associated with Loeys-Dietz syndrome type 4 demonstrated decreased corneal thickness, and in 2 cases with splice site mutations, also demonstrated cornea guttata. The data demonstrate the importance of considering distinct phenotype-genotype correlations within this condition.
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http://dx.doi.org/10.1016/j.jcjo.2020.03.007DOI Listing
August 2020

Preloading Trifolded Grafts for Descemet Membrane Endothelial Keratoplasty Affects Scroll Formation.

Cornea 2020 Aug;39(8):1062-1065

Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.

Purpose: The trifolded, endothelium-in approach to Descemet membrane endothelial keratoplasty (DMEK) facilitates tissue insertion into the anterior chamber. We hypothesized that preloading the trifolded donor grafts in a cartridge for 48 hours before insertion would induce biomechanical changes that decrease their scrolling tendency compared with those loaded immediately before insertion.

Methods: Ten Descemet membrane donor grafts, peeled and cut to 8.0 mm, were prepared by a single eye bank technician. Each graft was trifolded and pulled into a DMEK cartridge and stored for 48 hours. They were then pulled with microforceps into a petri dish filled with balanced salt solution. A video was recorded of the graft becoming a scroll over a 2-minute period. Each graft, serving as its own control, was then trifolded, pulled into the cartridge, and the process repeated. Images from 1, 5, 10, 60, and 120 seconds were extracted from video recording of the procedures. Scroll width was analyzed by graders masked to group assignment. A paired t test was used to determine differences in scroll width at each time point between the 48-hour and instant trifolding conditions.

Results: All grafts scrolled after removal from the cartridge into balanced salt solution. We measured a significant difference at all time points 1 through 120 seconds (4.02 preloaded vs. 2.91-mm instant trifold, P = 0.035).

Conclusions: Preloading DMEK grafts in a trifolded configuration for 48 hours reduces the scrolling tendency of Descemet membrane for at least 2 minutes.
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http://dx.doi.org/10.1097/ICO.0000000000002298DOI Listing
August 2020

Qualitative and Quantitative Analysis of the Corneal Endothelium With Smartphone Specular Microscopy.

Cornea 2020 Jul;39(7):924-929

Division of Cornea, Cataract and External Diseases, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD.

Purpose: We sought to demonstrate the feasibility of a lower-cost, portable method for qualitative and quantitative analysis of the corneal endothelium using a smartphone and slit-lamp biomicroscope.

Methods: In this study, at a single academic center, we recruited healthy participants to undergo imaging of the corneal endothelium using both a smartphone-based method and a specular microscope. Participants first had their eyes imaged with a CellChek NSP-9900 Specular Microscope (Konan Medical, Inc, Irvine, CA). For image capture on the smartphone, a beam of light approximately 0.2 mm in diameter was directed to the center of the cornea with a slit-lamp biomicroscope to achieve specular reflection. With 40× zoom on the slit-lamp and 4K video mode set on an iPhone 7 Plus held to an ocular, the corneal endothelium was recorded until the hexagonal pattern of cells was identified and the sharpest frame from the video was selected.

Results: The videos were analyzed from 14 sets of eyes (average length 2 minutes 40 seconds). The average intraclass correlation coefficient was 0.67 (95% confidence interval, 0.43-0.82). The mean difference between smartphone endothelial cell count and specular endothelial cell count was -209 cells/mm (SD = 483 cells/mm), which did not achieve significance (P = 0.14). A Bland-Altman analysis with simple linear regression showed no proportional bias when comparing the 2 modalities (coefficient = -0.20; t-value = -0.42; P = 0.68).

Conclusions: Smartphone specular microscopy is capable of qualitative and quantitative analysis of the corneal endothelium. Further refinement to standardize the light source and automate analysis will increase feasibility.
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http://dx.doi.org/10.1097/ICO.0000000000002277DOI Listing
July 2020

Clinical Outcomes Of Descemet Membrane Endothelial Keratoplasty Using The Bonfadini-Todd Injector For Graft Insertion.

Clin Ophthalmol 2019 20;13:1869-1876. Epub 2019 Sep 20.

Division of Cornea, Cataract and External Diseases, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Purpose: To evaluate the clinical outcomes of using an Alcon intraocular lens (IOL) B cartridge for graft insertion during Descemet membrane endothelial keratoplasty (DMEK).

Patients And Methods: We retrospectively reviewed medical charts of patients who underwent DMEK using the Bonfadini-Todd injector, composed of an Alcon IOL B cartridge connected to plastic tubing and a syringe, for graft insertion between May 2016 and August 2018. Patient demographics, diagnoses, donor information, visual acuity, intraocular pressure (IOP), graft position and attachment status, pachymetry, and postoperative complications were recorded.

Results: Twenty-four eyes of 23 patients with an average age of 72.8 ± 10.0 years (range, 48-87 years) were included. Mean follow-up duration was 13.3 ± 6.6 months (range, 3-26 months). Twenty-one (87.5%) patients had a primary diagnosis of Fuchs endothelial dystrophy, two (8.3%) patients had bullous keratopathy and one (4.2%) had Peter's anomaly. Sixteen (66.7%) cases combined phacoemulsification and IOL implantation. Best-corrected visual acuity improved from a median of 0.398 logMAR preoperatively to 0.097 logMAR (P <0.001) at last follow-up examination, and central corneal thickness decreased from a median of 651 μm to 533.5 μm (P <0.001). Nine of 24 patients (37.5%) required re-bubbling due to partial graft detachment with a mean time of 12.1 ± 9.2 days (range, 5-35 days). One patient (4.2%) developed graft failure after re-bubbling and underwent Descemet stripping endothelial keratoplasty.

Conclusion: The Alcon IOL B cartridge for DMEK graft insertion is safe and simple.
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http://dx.doi.org/10.2147/OPTH.S219742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759826PMC
September 2019

Comparison of a Smartphone Application with Ishihara Pseudoisochromatic Plate for Testing Colour Vision.

Neuroophthalmology 2019 Aug 19;43(4):235-239. Epub 2018 Nov 19.

Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

The Eye Handbook (EHB) is the most frequently downloaded smartphone application with diagnostic tools for eye-care providers. However, limited data exists validating the EHB test to gold standard colour vision testing. EHB and Ishihara colour vision tests were evaluated and compared under simulated colour vision loss through use of image processing software. Images of both tests were processed through ImageJ to 32 bit-grey scale and blue channel under split RBG channel to model total colour vision loss and red-green (R-G) deficiency, respectively. Two colour plates differentiated R-G deficiency from total colour blindness in EHB compared with eight Ishihara plates. Without colour information, correct numerals were identified in 3.5/15 EHB plates converted to 32-bit greyscale, versus 1/16 in Ishihara. We conclude EHB may underestimate colour vision loss severity in persons with normal contrast sensitivity compared to Ishihara. Eye-care providers need to be aware of the potential inconsistency compared to standardised methods, including limitations in differentiating patients with R-G colour deficiencies from total colour blindness.
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http://dx.doi.org/10.1080/01658107.2018.1529187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736124PMC
August 2019

ADAM3A copy number gains occur in a subset of conjunctival squamous cell carcinoma and its high grade precursors.

Hum Pathol 2019 12 5;94:92-97. Epub 2019 Sep 5.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Conjunctival squamous cell carcinoma (cSCC) and its precursors are among the most frequent ocular surface neoplasms worldwide. Copy gain of 8p11.22 and ADAM3A overexpression have been recently identified in invasive cSCC. We sought to study copy number gains using fluorescent in situ hybridization (FISH) in cSCC and the spectrum of precursor lesions. A total of 54 cases conjunctival squamous intraepithelial neoplasia (CIN), carcinoma in situ (CIS), or cSCC were studied using FISH with an ADAM3A (8p11 locus) probe and a chromosome 8 (Chr 8) centromere reference probe. Eighty one percent (44/54) of the cases presented in men and 19% (10/54) in women. The age at presentation ranged from 12 to 94 years (mean 65.5 years). Severe CIN was diagnosed in 45% (24/54) of the cases, followed by CIS in 31% (17/54), moderate CIN in 15% (8/54), invasive cSCC in 7% (4/54), and mild CIN in 2% (1/54). Nine (of 54) (17%) cases harbored ADAM3A or Chr 8 gains, with one of these cases demonstrating high level amplification. All ADAM3A alterations were restricted to high-grade lesions, including 2/17 (12%) cCIS, 1/4 (24%) cSCC, 5/24 (20%) severe CIN and 1/8 (12%) moderate CIN. Monosomy 8 was detected in 2 (4%) cases. No ADAM3A alterations were detected in non-neoplastic controls. Gains of ADAM3A/chromosome 8 occur in a subset of cSCC and its precursors. Alterations were present in high-grade lesions, sparing non-neoplastic conjunctiva and absent in tested controls. Thus, the specificity of this alteration as a biomarker for ocular SCC deserves further study.
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http://dx.doi.org/10.1016/j.humpath.2019.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917831PMC
December 2019

Periocular infantile hemangiomas: Characteristics, ocular sequelae, and outcomes.

Pediatr Dermatol 2019 Nov 25;36(6):830-834. Epub 2019 Aug 25.

Division of Pediatric Dermatology, Departments of Pediatrics and Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Objectives: To identify clinical factors associated with complications of periocular infantile hemangioma (IH) and monitor improvement in complication rates post-treatment.

Methods: Retrospective cohort study. Eighty-nine patients diagnosed with periocular IH at a pediatric dermatology clinic of a tertiary care center between 2001 and 2013 were included with parental approval. Parents were interviewed by telephone between July and September of 2015, then again in January 2018 to inquire about ophthalmologic follow-up. Electronic medical records were reviewed from January 2001 through January 2018.

Results: Sixty percent of patients demonstrated ocular sequelae, including astigmatism (33%), visual axis obstruction (29%), nasolacrimal duct obstruction (7%), ptosis (4%), amblyopia (3%), and strabismus (1%). Compared with superficial IH, deep and mixed IH had higher odds, 3.4 (P = 0.025) and 3.8 (P = 0.034), respectively, of developing ocular sequelae. All patients with astigmatism prior to involution of IH received systemic therapy, with a significant post-treatment decrease in the proportion of patients with astigmatism (40% to 18%, P = 0.027). Three-quarters of patients experienced complete IH involution by time of enrollment in kindergarten. Fifty-one (57.3%) patients received formal ophthalmologic evaluation confirmed through chart review or phone interview, with average follow-up duration of 51.2 months (range: 1.9, 99.3).

Conclusion: Deep and mixed IH were more likely to demonstrate ocular complications than superficial IH. Rate of astigmatism decreased with systemic therapy. Our study suggests that patients with periocular IH have a lower rate of amblyopia now compared with the prepropranolol era and emphasizes the importance of early treatment of periocular IH to prevent permanent visual sequelae.
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http://dx.doi.org/10.1111/pde.13925DOI Listing
November 2019

Monoclonal gammopathy of "ocular" significance.

Am J Ophthalmol Case Rep 2019 Sep 20;15:100471. Epub 2019 May 20.

The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Woods 371, Baltimore, MD, 21287, USA.

Purpose: Diagnostic criteria for monoclonal gammopathy of undetermined significance (MGUS) do not currently include ocular phenotypic changes. Here, we offer a new diagnostic approach that is useful in patients with posteriorly located corneal depositions and present evidence to support the theory that the aqueous humor is a source for monoclonal proteins accumulated in the cornea.

Observations: A 77-year-old woman presented to the clinic with a gradual decrease in visual acuity over 6 months. Slit lamp examination revealed bilateral central guttae consistent with Fuchs corneal dystrophy, peripheral circular band-like corneal opacities in the deep stroma, and bilateral nuclear sclerotic and cortical cataracts. Anterior segment optical coherence tomography confirmed corneal opacities in the posterior stroma and Descemet membrane. Immunological studies revealed increased serum IgG levels of 3220 mg/dL and serum electrophoresis showed an abnormal monoclonal band of 2.4 g/dL identified as IgG lambda by immunofixation electrophoresis. The patient was referred to the hematology clinic where she underwent further systemic workup and was diagnosed with MGUS. Immunofixation electrophoresis of aqueous sampling, which was performed at the time of cataract surgery, confirmed the presence of the IgG lambda gammopathy in the anterior chamber.

Conclusions And Importance: Monoclonal gammopathy, although rare, should be included in the differential diagnosis of corneal opacities, as the ocular finding can be the initial manifestation of a systemic disease that can potentially be life-threatening. When corneal biopsy is not feasible due to the location of corneal pathology, aqueous sampling may be an alternative approach towards a clinical diagnosis. We propose a new terminology, "monoclonal gammopathy of ocular significance," for patients diagnosed with MGUS, however, their only significant clinical finding is ocular manifestation.
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http://dx.doi.org/10.1016/j.ajoc.2019.100471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535680PMC
September 2019

Prognostic factors and survival for malignant conjunctival melanoma and squamous cell carcinoma over four decades.

Am J Otolaryngol 2019 Jul - Aug;40(4):577-582. Epub 2019 May 15.

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Purpose: To determine the epidemiology and survival of primary conjunctival malignant neoplasms.

Methods: Retrospective analysis of primary malignant conjunctival neoplasms using Surveillance, Epidemiology, and End Results database from 1973 to 2012.

Results: Of 1661 cases, the most common neoplasms are squamous cell carcinoma (SCC) at 54.8% and melanoma at 38.8%. Mean diagnostic age for melanoma was 62.1 compared to 65.5 years for SCC (p = 0.002). 52.2% of melanoma are male versus 77.4% of SCC (p < 0.001). For SCC only age (HR: 1.09, 95% CI:1.04-1.14) is a predictor of survival. For melanoma, age (HR: 1.07, 95% CI: 1.05-1.10), male sex (HR: 2.04, 95% CI: 1.16-3.60), T4 tumors (HR: 3.38, 95% CI: 1.17-9.80) and N1 status (HR: 8.69, 95% CI: 2.75-27.42) are all survival predictors. The 5 and 10-year overall survival (OS) estimates are not significantly different between SCC and melanoma, with 70% and 50% respectively for SCC, and 71% and 50% respectively for melanoma. Median survival time is worse for blacks (52 months) compared to whites (118 months) and Asians/Native Americans/Pacific Islanders (145 months), however race was not found to be a significant prognostic factor in multivariate analysis. Five-year survival are similar between decades 1973-1982 (66.2%), 1983-1992 (69.2%), 1993-2002 (71.3%) and 2003-2012 (70.2%).

Conclusion: Age at diagnosis is a determinant of survival for both conjunctival SCC and melanoma. Male sex, T4 and N1 staging are also important prognostic factors for melanoma. With respect to overall survival, SCC and melanoma did not differ significantly.
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http://dx.doi.org/10.1016/j.amjoto.2019.05.013DOI Listing
December 2019

Endothelial keratoplasty for corneal endothelial dystrophy in a dog.

Vet Ophthalmol 2019 Jul 10;22(4):545-551. Epub 2019 Apr 10.

Johns Hopkins Wilmer Eye Institute, Baltimore, Maryland.

Objective: To assess the efficacy of an endothelial keratoplasty procedure at defined intervals to 1 year postoperatively for the treatment of corneal endothelial dystrophy (CED) in a canine patient.

Procedure: A dog diagnosed with CED with progressive corneal edema underwent an endothelial keratoplasty. The patient was examined pre- and postoperatively with slit lamp biomicroscopy and ultrasonic pachymetry.

Results: Mean central corneal thickness (CCT) measured with pachymetry was >1400 μm preoperatively and decreased postoperatively to 725 μm. The transplanted donor tissue became transparent 2 weeks postoperatively and incorporated with the recipient cornea. The graft remained transparent throughout the duration of the postoperative period evaluated in this study (2 weeks postoperatively to 1 year). The canine patient was comfortable pre- and postoperatively.

Conclusions: Endothelial keratoplasty is a potential therapeutic option for canine cases with progressive corneal thickening due to CED. As this is a single case study, further investigation into the use of endothelial keratoplasty to treat CED is warranted. Moreover, canine patients with CED might serve as a surgical model for human patients with Fuchs' Endothelial Corneal Dystrophy.
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http://dx.doi.org/10.1111/vop.12670DOI Listing
July 2019

A Longitudinal Study of Ebola Sequelae in Liberia.

N Engl J Med 2019 03;380(10):924-934

The affiliations of the members of the writing committee are as follows: National Institutes of Health, Bethesda (M.C.S., R.J.B., L.E.H., E.S.H., A.N., K.T., J.V., K.S.J., B.D.-K., H.C.L.), and Johns Hopkins University, Ophthalmology, Baltimore (A.O.E.) - both in Maryland; Division of Biostatistics, University of Minnesota, Minneapolis (C.R., J.D.N.); and Liberian Ministry of Health (M.B., M.P.F.) and John F. Kennedy Medical Center (S.J.M.), Monrovia, the Duport Road Clinic, Paynesville (D.G.-D.), and C.H. Rennie Hospital, Kakata (K.L.J.) - all in Liberia.

Background: Multiple health problems have been reported in survivors of Ebola virus disease (EVD). Attribution of these problems to the disease without a control group for analysis is difficult.

Methods: We enrolled a cohort of EVD survivors and their close contacts and prospectively collected data on symptoms, physical examination findings, and laboratory results. A subset of participants underwent ophthalmologic examinations. Persistence of Ebola virus (EBOV) RNA in semen samples from survivors was determined.

Results: A total of 966 EBOV antibody-positive survivors and 2350 antibody-negative close contacts (controls) were enrolled, and 90% of these participants were followed for 12 months. At enrollment (median time to baseline visit, 358 days after symptom onset), six symptoms were reported significantly more often among survivors than among controls: urinary frequency (14.7% vs. 3.4%), headache (47.6% vs. 35.6%), fatigue (18.4% vs. 6.3%), muscle pain (23.1% vs. 10.1%), memory loss (29.2% vs. 4.8%), and joint pain (47.5% vs. 17.5%). On examination, more survivors than controls had abnormal abdominal, chest, neurologic, and musculoskeletal findings and uveitis. Other than uveitis (prevalence at enrollment, 26.4% vs. 12.1%; at year 1, 33.3% vs. 15.4%), the prevalence of these conditions declined during follow-up in both groups. The incidence of most symptoms, neurologic findings, and uveitis was greater among survivors than among controls. EBOV RNA was detected in semen samples from 30% of the survivors tested, with a maximum time from illness to detection of 40 months.

Conclusions: A relatively high burden of symptoms was seen in all participants, but certain symptoms and examination findings were more common among survivors. With the exception of uveitis, these conditions declined in prevalence during follow-up in both groups. Viral RNA in semen persisted for a maximum of 40 months. (Funded by the National Institute of Allergy and Infectious Diseases and the National Eye Institute; PREVAIL III ClinicalTrials.gov number, NCT02431923.).
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http://dx.doi.org/10.1056/NEJMoa1805435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478393PMC
March 2019

Aspiration of Tri-folded, Endothelium-In Grafts for Descemet Membrane Endothelial Keratoplasty.

Cornea 2019 May;38(5):654-657

Wilmer Eye Institute at Johns Hopkins, Baltimore, MD.

Purpose: In Descemet membrane endothelial keratoplasty (DMEK), loading and positioning of tri-folded grafts into a cartridge is generally conducted with forceps or a hook, risking graft tear or trauma. We demonstrate the feasibility of loading tri-folded grafts into a cartridge with no touch to the endothelium required beyond the tri-folding process.

Methods: A corneoscleral rim with a prestripped DMEK graft is placed into a petri dish. After the graft is tri-folded with forceps and removed from its stromal attachment, the graft is gently wicked into the tip of a saline-filled Alcon B IOL cartridge connected to IV extension tubing and a 3 cc syringe, drawn into the cartridge by positioning it adjacent to the graft tip. The remainder of the graft is aspirated with the addition of saline. The cartridge orientation is reversed for graft injection. In this retrospective analysis, we analyzed surgical videos for preparation times, and assessed postoperative visual acuity, pachymetry, and endothelial cell density.

Results: Thirteen cases underwent this approach. Median preparation time from stain to cartridge eye contact was 8.5 minutes, and time from graft injection to final centration and bubbling was 2.9 minutes. Corneal thickness decreased from a median of 623 microns preoperatively to 566 μm at 1 month (P = 0.038). Visual acuity improved by 1 month by a median of 0.3 logarithm of the minimum angle of resolution (logMAR) (P = 0.016). Endothelial cell density decreased by 32.4% at 1 month compared with baseline.

Conclusions: Endothelium-in DMEK grafts may be loaded into a plastic cartridge using a skill set similar to aspiration of a scroll.
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http://dx.doi.org/10.1097/ICO.0000000000001888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443421PMC
May 2019

Pilot Study of Audiometric Patterns in Fuchs Corneal Dystrophy.

J Speech Lang Hear Res 2018 10;61(10):2604-2608

The Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD.

Purpose: Although Fuchs corneal dystrophy (FCD) is considered an eye disease, a small number of studies have identified genes related to both FCD and hearing loss. Whether FCD is related to hearing loss is unknown.

Method: This is a case-control study comparing pure-tone audiometry hearing thresholds in 180 patients with FCD from a hospital-based ophthalmology clinic with 2,575 population-based controls from a nationally representative survey, the National Health and Nutrition Examination Survey (from cycles 2005-06 and 2009-10). Generalized estimating equations were used to compare mean better-hearing ear thresholds in the 2 groups adjusted for age, sex, race, and noise exposure.

Results: Patients with FCD had higher hearing thresholds (worse hearing) in lower frequencies (mean difference at 0.5 kHz = 3.49 dB HL) and lower hearing thresholds (better hearing) in higher frequencies (difference at 4 kHz = -4.25 dB HL) compared with population-based controls.

Conclusion: In the first study to use objectively measured hearing, FCD was associated with poorer low-frequency and better high-frequency audiometric thresholds than population controls. Further studies are needed to characterize this relationship.
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http://dx.doi.org/10.1044/2018_JSLHR-H-18-0088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428237PMC
October 2018

Clinical and genetic investigation of amantadine-associated corneal edema.

Clin Ophthalmol 2018 6;12:1367-1371. Epub 2018 Aug 6.

Division of Cornea, Cataract, & External Diseases, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA,

Purpose: Amantadine use has been temporally associated with bilateral corneal edema in a series of cases; however, its pathophysiological mechanisms have yet to be elucidated. We sought to rule out subclinical Fuchs dystrophy as a contributor, characterize its pattern of corneal edema, and describe the long-term outcome of concurrent topical steroids while resuming amantadine.

Patient And Methods: After a 44-year-old woman presented with new acute onset bilateral corneal edema, amantadine was discontinued, with clinical improvement. However, neurological decompensation required restarting amantadine, which she did concurrently with topical loteprednol. To determine whether subclinical Fuchs dystrophy might be present, triplet-primed polymerase chain reaction was conducted to measure copy number of the CTG18.1 trinucleotide repeat in . Specular microscopy and Scheimpflug imaging were conducted and followed for 32 months to assess for resolution and stability. Literature review was conducted to assess for consistency of the clinical phenotype.

Results: Corneal edema resolved clinically 4 weeks after discontinuation of amantadine. Serial Scheimpflug imaging demonstrated resolution of posterior and central corneal edema and specular microscopy revealed intracellular opacities with loss of endothelial cell density. Despite resuming amantadine, Scheimpflug imaging and specular microscopy measurements remained stable at 32 months. Triplet-primed PCR of CTG18.1 in revealed no trinucleotide repeat expansion.

Conclusions: Amantadine-associated corneal edema is characteristically posterior and central and appears unlikely to represent early or subclinical decompensation of Fuchs dystrophy. We describe the unique outcome of continued corneal clearance after restarting amantadine concurrently with steroids, a pattern that has persisted over 32 months to date.
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http://dx.doi.org/10.2147/OPTH.S166384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084078PMC
August 2018

Identification of a Novel TCF4 Isoform in the Human Corneal Endothelium.

Cornea 2018 Jul;37(7):899-903

The Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.

Purpose: Alternative splice isoforms of TCF4, a gene implicated in Fuchs corneal dystrophy, have been identified in multiple human tissues outside of the eye. The aim of this study was to identify the transcriptional profile of TCF4 in the corneal endothelium.

Methods: We extracted RNA from the donor corneal endothelium and performed rapid amplification of cDNA ends. We tested the expression pattern of 1 newly identified isoform (7b) in a panel of cDNA derived from multiple human tissues and included cDNA from corneal endothelial (CE) and retinal pigment epithelial cell lines. To further delineate differential expression of TCF4 splice variants that span CTG18.1, we analyzed expression of 6 alternative splice isoforms that are transcribed from either exon 2 or 3 in RNA extracted from the corneal endothelium of 3 normal donors and a CE cell line.

Results: We identified 11 different isoforms in control CE tissue, including 1 isoform (7b) not reported previously. This isoform is enriched specifically in the corneal endothelium and placenta compared with other tissues in a panel of human cDNA.

Conclusions: We demonstrate the complex expression profile of TCF4 in the human corneal endothelium and reveal expression of alternative splice variants of TCF4.
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http://dx.doi.org/10.1097/ICO.0000000000001521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482941PMC
July 2018

Effects of Contrast Sensitivity on Colour Vision Testing.

Neuroophthalmology 2017 Aug 19;41(4):182-186. Epub 2017 May 19.

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

This study analyses how contrast sensitivity loss affects colour vision (CV) testing. Eleven participants were scored while cycling through randomly arranged pictures of CV tests with varying levels of contrast changes applied. Hardy-Rand-Rittler (HRR) scores declined significantly at each successive decrease in contrast level after the highest setting ( < 0.004). HRR scores were also lower than those for Ishihara and Farnsworth D-15 tests at two contrast settings ( < 0.01). Contrast changes had the greatest impact on HRR scores, indicating that this test may not be an accurate reflection of CV in patients with contrast sensitivity loss.
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http://dx.doi.org/10.1080/01658107.2017.1295273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762144PMC
August 2017

CTG18.1 Expansion in TCF4 Among African Americans With Fuchs' Corneal Dystrophy.

Invest Ophthalmol Vis Sci 2017 12;58(14):6046-6049

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.

Purpose: Studies of Fuchs' dystrophy have largely focused on individuals of European origin. Characterization of disease among African Americans is required to ensure prognostic factors and therapeutic approaches are applicable across diverse patient populations.

Methods: We assessed all self-reported black and white patients aged older than 40 years at a tertiary care institution with a diagnosis of cataract over a 3-year period for concurrent diagnosis of Fuchs' dystrophy. Affected patients in a longitudinal cohort were invited to provide a blood sample from which we extracted genomic DNA. The CTG18.1 trinucleotide repeat length was determined using a two-step, triplet repeat primed PCR protocol. Expansion was defined as >40 CTG repeats. Demographic information, including race, was documented.

Results: Of 59,365 self-reported black and white adults who presented for cataract evaluation, the odds ratio of presenting with Fuchs' dystrophy among black compared to white patients was 0.6992 (95% confidence interval [CI], 0.6210-0.7872). A total of 60 black and 549 white patients with Fuchs' corneal dystrophy enrolled in the longitudinal study, of which 21 (35.0%) black and 343 (62.5%) white patients demonstrated trinucleotide repeat expansion, a significant difference (P = 7.7 × 10-5). In a multivariable linear regression model, repeat expansion but not race was significantly associated with mean clinical grading of severity.

Conclusions: Black patients with Fuchs' dystrophy were less likely than white patients to demonstrate CTG18.1 allele expansion. The data contribute to our understanding of population differences in clinical presentation, and highlight the need for considering diversity of patient populations in clinical research.
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http://dx.doi.org/10.1167/iovs.17-21661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710628PMC
December 2017

Effects of temperature and fluid media on the scroll width size of the Descemet's membrane endothelial keratoplasty (DMEK) donor graft.

Clin Ophthalmol 2017 1;11:1611-1615. Epub 2017 Sep 1.

KeraLink International, Baltimore, MD, USA.

Aim: Our study was conducted to evaluate whether higher temperature leads to increased - or wider - scroll widths of the Descemet's membrane endothelial keratoplasty (DMEK) donor graft.

Purpose: To investigate the effects of temperature and fluid media on the DMEK donor graft scroll widths.

Materials And Methods: This research work was a laboratory investigation. Baseline cell count was taken via specular microscopy for the donor corneas at room temperature (20°C-25°C). The endothelium sides of the donor corneas were stained with Trypan Blue Solution 0.4% for 30 s, and the Descemet's membranes were stripped. The DMEK donor grafts were placed into three different fluid media - Optisol, Balanced Salt Solution (BSS), and BSS PLUS (BSS Plus). The DMEK donor grafts were then transferred into cold temperature (4°C) for 60 min, after which the donor grafts' scroll widths were examined and measured. The donor grafts were then warmed in the incubator and brought to physiological temperature (35°C-37°C), and their scroll widths were examined and measured again.

Results: In 30 measurements of ten tissues across three temperature and fluid conditions, the average scroll width measured 1.73 mm, ranging from 1.1 to 2.9 mm. In a mixed linear model, the scroll widths increased with temperature (=0.02). There was no significant difference in scroll widths among the three solutions (=0.84, mixed linear model).

Conclusion: We observed an increase in DMEK donor graft scroll widths with higher temperatures. The usage of BSS Plus as media solution could also lead to smaller DMEK donor graft scroll widths, compared with BSS, but our study does not establish this.
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http://dx.doi.org/10.2147/OPTH.S143427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589108PMC
September 2017

GOOGLE CARDBOARD INDIRECT OPHTHALMOSCOPY.

Retina 2017 Aug;37(8):1617-1619

Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1097/IAE.0000000000001772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544528PMC
August 2017

Deletion at the GCNT2 Locus Causes Autosomal Recessive Congenital Cataracts.

PLoS One 2016 9;11(12):e0167562. Epub 2016 Dec 9.

The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.

Purpose: The aim of this study is to identify the molecular basis of autosomal recessive congenital cataracts (arCC) in a large consanguineous pedigree.

Methods: All participating individuals underwent a detailed ophthalmic examination. Each patient's medical history, particularly of cataracts and other ocular abnormalities, was compiled from available medical records and interviews with family elders. Blood samples were donated by all participating family members and used to extract genomic DNA. Genetic analysis was performed to rule out linkage to known arCC loci and genes. Whole-exome sequencing libraries were prepared and paired-end sequenced. A large deletion was found that segregated with arCC in the family, and chromosome walking was conducted to estimate the proximal and distal boundaries of the deletion mutation.

Results: Exclusion and linkage analysis suggested linkage to a region of chromosome 6p24 harboring GCNT2 (glucosaminyl (N-acetyl) transferase 2) with a two-point logarithm of odds score of 5.78. PCR amplifications of the coding exons of GCNT2 failed in individuals with arCC, and whole-exome data analysis revealed a large deletion on chromosome 6p in the region harboring GCNT2. Chromosomal walking using multiple primer pairs delineated the extent of the deletion to approximately 190 kb. Interestingly, a failure to amplify a junctional fragment of the deletion break strongly suggests an insertion in addition to the large deletion.

Conclusion: Here, we report a novel insertion/deletion mutation at the GCNT2 locus that is responsible for congenital cataracts in a large consanguineous family.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167562PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147899PMC
July 2017

Mutation in LIM2 Is Responsible for Autosomal Recessive Congenital Cataracts.

PLoS One 2016 4;11(11):e0162620. Epub 2016 Nov 4.

The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, United States of America.

Purpose: To identify the molecular basis of non-syndromic autosomal recessive congenital cataracts (arCC) in a consanguineous family.

Methods: All family members participating in the study received a comprehensive ophthalmic examination to determine their ocular phenotype and contributed a blood sample, from which genomic DNA was extracted. Available medical records and interviews with the family were used to compile the medical history of the family. The symptomatic history of the individuals exhibiting cataracts was confirmed by slit-lamp biomicroscopy. A genome-wide linkage analysis was performed to localize the disease interval. The candidate gene, LIM2 (lens intrinsic membrane protein 2), was sequenced bi-directionally to identify the disease-causing mutation. The physical changes caused by the mutation were analyzed in silico through homology modeling, mutation and bioinformatic algorithms, and evolutionary conservation databases. The physiological importance of LIM2 to ocular development was assessed in vivo by real-time expression analysis of Lim2 in a mouse model.

Results: Ophthalmic examination confirmed the diagnosis of nuclear cataracts in the affected members of the family; the inheritance pattern and cataract development in early infancy indicated arCC. Genome-wide linkage analysis localized the critical interval to chromosome 19q with a two-point logarithm of odds (LOD) score of 3.25. Bidirectional sequencing identified a novel missense mutation, c.233G>A (p.G78D) in LIM2. This mutation segregated with the disease phenotype and was absent in 192 ethnically matched control chromosomes. In silico analysis predicted lower hydropathicity and hydrophobicity but higher polarity of the mutant LIM2-encoded protein (MP19) compared to the wild-type. Moreover, these analyses predicted that the mutation would disrupt the secondary structure of a transmembrane domain of MP19. The expression of Lim2, which was detected in the mouse lens as early as embryonic day 15 (E15) increased after birth to a level that was sustained through the postnatal time points.

Conclusion: A novel missense mutation in LIM2 is responsible for autosomal recessive congenital cataracts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162620PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096708PMC
June 2017

Automated Retroillumination Photography Analysis for Objective Assessment of Fuchs Corneal Dystrophy.

Cornea 2017 Jan;36(1):44-47

*Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD; †George Washington University School of Medicine & Health Sciences, Washington, DC; ‡Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; §Department of Medicine, University of California Irvine, Irvine, CA; and ¶University of Maryland, College Park, MD.

Purpose: Retroillumination photography analysis is an objective tool for the assessment of the number and distribution of guttae in eyes affected with Fuchs corneal dystrophy (FCD). Current protocols include manual processing of images; here, we assess validity and interrater reliability of automated analysis across various levels of FCD severity.

Methods: Retroillumination photographs of 97 FCD-affected corneas were acquired, and total counts of guttae were previously summated manually. For each cornea, a single image was loaded into ImageJ software. We reduced color variability and subtracted background noise. Reflection of light from each gutta was identified as a local area of maximum intensity and counted automatically. Noise tolerance level was titrated for each cornea by examining a small region of each image with automated overlay to ensure appropriate coverage of individual guttae. We tested interrater reliability of automated counts of guttae across a spectrum of clinical and educational experience.

Results: A set of 97 retroillumination photographs was analyzed. Clinical severity as measured by a modified Krachmer scale ranged from a severity level of 1 to 5 in the set of analyzed corneas. Automated counts by an ophthalmologist correlated strongly with Krachmer grading (R = 0.79) and manual counts (R = 0.88). Intraclass correlation coefficients demonstrated strong correlation at 0.924 (95% CI, 0.870-0.958) among cases analyzed by 3 students, and 0.869 (95% CI, 0.797-0.918) among cases for which images were analyzed by an ophthalmologist and 2 students.

Conclusions: Automated retroillumination photography analysis allows for grading of FCD severity with high resolution across a spectrum of disease severity.
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http://dx.doi.org/10.1097/ICO.0000000000001056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138098PMC
January 2017

CTG18.1 Expansion in TCF4 Increases Likelihood of Transplantation in Fuchs Corneal Dystrophy.

Cornea 2017 Jan;36(1):40-43

*Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD; and †Department of Biostatistics, Johns Hopkins University School of Public Health, Baltimore, MD.

Purpose: Fuchs dystrophy is the leading indication of corneal transplantation in the United States. A CTG18.1 trinucleotide repeat in TCF4 correlates with increased severity in Fuchs dystrophy; however, quantitative estimates of increased transplantation risk, including effects of age and sex, are unclear.

Methods: In a tertiary institution clinical practice, 574 participants were enrolled in a longitudinal study of Fuchs dystrophy after slit-lamp biomicroscopy confirmed significant central guttae and/or corneal transplantation in both eyes. We documented clinical history, examination findings, and demographic information. We acquired blood samples, extracted DNA, and sequenced the CTG18.1 trinucleotide repeat in TCF4. In this retrospective case-control study, the number of participants with triplet expansion, defined as greater than 40 CTG repeats, and transplantation status were assessed. Kaplan-Meier estimates of timing and transplantation events were produced. The Cox proportional hazard regression model was used to assess the relationship between age, sex, triplet expansion, and surgery.

Results: A total of 106 participants (18.5%) previously underwent corneal transplantation in at least 1 eye at the time of initial evaluation. A higher proportion of individuals harboring allele expansion had undergone transplantation (78/357, 21.8%) compared with those without the expanded allele (28/217, 12.9%), a significant association (P = 0.007). The log-rank test demonstrates a significant difference in survival function over time (P = 0.027), with a hazard ratio of 1.64 (95% confidence interval, 1.05-2.55).

Conclusions: Expansion of the TCF4 CTG trinucleotide repeat was associated with 1.64 times higher likelihood of corneal transplantation at a given age in patients with Fuchs dystrophy.
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http://dx.doi.org/10.1097/ICO.0000000000001049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138126PMC
January 2017

Distinct Clinical Phenotype of Corneal Dystrophy Predicts the p.(Leu450Trp) Substitution in COL8A2.

Cornea 2016 May;35(5):587-91

Wilmer Ophthalmological Institute, Baltimore, MD.

Purpose: The p.(Leu450Trp) substitution in Collagen, Type VIII, Alpha 2 (COL8A2) is associated with an early-onset corneal dystrophy. Here we identify distinct anterior corneal and keratorefractive changes associated with this disease and replicate its distinguishing endothelial characteristics in a new family.

Methods: We reviewed clinical data from a large family associated with the p.(Leu450Trp) COL8A2 mutation. We compared clinical photographs and keratometry over an 11-year period. We sought to replicate these findings, and after a 40-year-old male subject presented similarly, we obtained a peripheral blood sample and sequenced COL8A2.

Results: Of 10 individuals with the p.(Leu450Trp) substitution, clinical records noted corneal edema in 6, of which 4 showed epithelial microcystic edema. Eleven-year progression data reveal a marked increase in subepithelial corneal edema and gradual, profound increase in anterior corneal astigmatism. Sequencing of genomic DNA from the unrelated individual predictably identified a c.1349T>G [p.(Leu450Trp)] heterozygous variation in COL8A2. Confocal microscopy confirmed attenuated endothelium, and histopathology revealed no guttae, consistent with findings from a previously identified family.

Conclusions: Peripheral, anterior microcystic corneal edema represents a characteristic aspect of the phenotype associated with the p.(Leu450Trp) substitution in COL8A2, in at least 2 of 3 known affected families worldwide. We describe long-term progression and Descemet stripping endothelial keratoplasty for this disease for the first time.
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http://dx.doi.org/10.1097/ICO.0000000000000796DOI Listing
May 2016

Smartphone-Based Visual Acuity Measurement for Screening and Clinical Assessment.

JAMA 2015 Dec 22-29;314(24):2682-3

Department of International Health and Department of Epidemiology, Bloomberg School of Public Health, Baltimore, Maryland.

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http://dx.doi.org/10.1001/jama.2015.15855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913699PMC
January 2016