Publications by authors named "Scott D Walter"

26 Publications

  • Page 1 of 1

Mutations in SREBF1, Encoding Sterol Regulatory Element Binding Transcription Factor 1, Cause Autosomal-Dominant IFAP Syndrome.

Am J Hum Genet 2020 07 3;107(1):34-45. Epub 2020 Jun 3.

Department of Dermatology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Diseases, Beijing 100034, China. Electronic address:

IFAP syndrome is a rare genetic disorder characterized by ichthyosis follicularis, atrichia, and photophobia. Previous research found that mutations in MBTPS2, encoding site-2-protease (S2P), underlie X-linked IFAP syndrome. The present report describes the identification via whole-exome sequencing of three heterozygous mutations in SREBF1 in 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. SREBF1 encodes sterol regulatory element-binding protein 1 (SREBP1), which promotes the transcription of lipogenes involved in the biosynthesis of fatty acids and cholesterols. This process requires cleavage of SREBP1 by site-1-protease (S1P) and S2P and subsequent translocation into the nucleus where it binds to sterol regulatory elements (SRE). The three detected SREBF1 mutations caused substitution or deletion of residues 527, 528, and 530, which are crucial for S1P cleavage. In vitro investigation of SREBP1 variants demonstrated impaired S1P cleavage, which prohibited nuclear translocation of the transcriptionally active form of SREBP1. As a result, SREBP1 variants exhibited significantly lower transcriptional activity compared to the wild-type, as demonstrated via luciferase reporter assay. RNA sequencing of the scalp skin from IFAP-affected individuals revealed a dramatic reduction in transcript levels of low-density lipoprotein receptor (LDLR) and of keratin genes known to be expressed in the outer root sheath of hair follicles. An increased rate of in situ keratinocyte apoptosis, which might contribute to skin hyperkeratosis and hypotrichosis, was also detected in scalp samples from affected individuals. Together with previous research, the present findings suggest that SREBP signaling plays an essential role in epidermal differentiation, skin barrier formation, hair growth, and eye function.
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http://dx.doi.org/10.1016/j.ajhg.2020.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332643PMC
July 2020

Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab.

Ophthalmology 2020 10 25;127(10):1345-1359. Epub 2020 Apr 25.

Bascom Palmer Eye Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.

Purpose: To evaluate features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6 mg/0.05 ml for treatment of neovascular age-related macular degeneration.

Design: Retrospective case series.

Participants: Fifteen eyes from 12 patients identified from 10 United States centers.

Methods: Review of patient demographics, ophthalmologic examination results, and retinal imaging findings.

Main Outcome Measures: Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography results, and treatment strategies.

Results: The number of previous anti-VEGF IVIs ranged between 2 and 80 in the affected eye before switching to brolucizumab. Retinal vasculitis and IOI were diagnosed at a mean of 30 days after brolucizumab IVI. Mean VA before brolucizumab IVI was 0.426 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/53) and VA at diagnosis of retinal vasculitis was 0.981 logMAR (Snellen equivalent, 20/191; range, 20/25-20/1600; P = 0.008). All affected eyes showed IOI with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages, and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular nonperfusion, and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients, and 3 patients showed negative laboratory assessment for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, and topical), and 2 eyes underwent vitrectomy without improvement in vision. After a mean follow-up of 25 days, mean VA was 0.833 logMAR (Snellen equivalent, 20/136), which was reduced compared with baseline (P = 0.033).

Conclusions: Retinal vasculitis and IOI after brolucizumab IVI are characterized by variable occlusion of large or small retinal arteries, or both, and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required because vitreous cells may obscure visualization of retinal details.
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http://dx.doi.org/10.1016/j.ophtha.2020.04.017DOI Listing
October 2020

Intraocular Dissemination of Uveal Melanoma Cells Following Radiotherapy: Evolving Management Over the Past Decade.

Ophthalmic Surg Lasers Imaging Retina 2019 09;50(9):573-579

Background And Objective: To describe the presentation and the authors' evolving management strategy for intraocular dissemination of uveal melanoma cells following radiotherapy during the past decade.

Patients And Methods: Patients with uveal melanoma who developed intraocular dissemination of pigmented cells following radiotherapy. Histopathology was available in two cases.

Results: Four patients underwent treatment for progressive intraocular dissemination of uveal melanoma cells at 9 to 41 months following I-125 plaque radiotherapy (three patients) or proton beam radiotherapy (one patient). Treatments included primary enucleation (one patient), vitrectomy followed later by enucleation (one patient), and vitrectomy followed by intravitreal chemotherapy (two patients). Enucleated eyes demonstrated diffuse invasion of intraocular tissues by viable melanoma cells. No patient has developed systemic metastasis to date.

Conclusions: Intraocular dissemination of pigmented cells following radiotherapy for uveal melanoma should raise suspicion for viable invasive melanoma cells. Prompt vitrectomy with intravitreal chemotherapy can be effective in avoiding enucleation in selected cases. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:573-579.].
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http://dx.doi.org/10.3928/23258160-20190905-06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790979PMC
September 2019

Intraocular Metastasis in Unilateral Multifocal Uveal Melanoma Without Melanocytosis or Germline BAP1 Mutations.

JAMA Ophthalmol 2019 Oct 3. Epub 2019 Oct 3.

Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida.

Importance: There has been speculation on the pathogenesis of unilateral multifocal uveal melanoma, but there remains no convincing explanation. Genetic analysis suggests that unilateral multifocal uveal melanoma may represent intraocular metastasis with increased risk of systemic metastasis.

Objective: To evaluate the pathogenesis of unilateral multifocal uveal melanoma.

Design, Setting, And Participants: This clinical case series was conducted in tertiary academic ocular oncology referral centers and included patients with unilateral multifocal uveal melanoma.

Main Outcomes And Measures: Gene expression and mutation profiling of tumor samples.

Results: Four patients (all male; age range, 54-77 years) who were diagnosed with uveal melanoma were treated with plaque brachytherapy, and subsequently developed a second discrete uveal melanoma in the same eye were included. None demonstrated ocular or oculodermal melanocytosis. All 8 tumors available for analysis exhibited class 2 gene expression profiles. In all 4 cases, the initial and subsequent tumors were available for targeted DNA sequencing and identical driver mutations were present in both tumors. Data were collected from September 2015 to August 2018.

Conclusions And Relevance: Unilateral multifocal uveal melanoma in the absence of ocular melanocytosis appears to occur preferentially in tumors with the class 2 gene expression profile and a BRCA1-associated protein 1 gene (BAP1) mutation. The presence of identical BAP1 mutations in multiple tumors in the same eye in the absence of a germline BAP1 mutation suggests intraocular metastasis rather than independent primary tumors. These findings indicate that the first site of metastasis can be within the eye itself and suggest that patients with unilateral multifocal uveal melanoma may be at increased risk of systemic metastasis.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.3941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777244PMC
October 2019

Association of Nonuveitic Retinal Vasculitis and Tractional Retinoschisis With Cystoid Macular Edema With Fabry Disease.

JAMA Ophthalmol 2019 Jul 3. Epub 2019 Jul 3.

Duke Eye Center, Duke University, Department of Ophthalmology, Durham, North Carolina.

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http://dx.doi.org/10.1001/jamaophthalmol.2019.2170DOI Listing
July 2019

Dosimetric comparison of circular Eye Physics and Collaborative Ocular Melanoma Study plaques to treat uveal melanoma.

Brachytherapy 2019 May - Jun;18(3):404-410. Epub 2019 Feb 20.

Department of Radiation Oncology, University of Miami/Jackson Memorial Hospital, Miami, FL. Electronic address:

Purpose: We sought to formally compare Collaborative Ocular Melanoma Study (COMS) and similar-shaped (circular) eye physics (EP) plaques dosimetrically by examining both tumor coverage and critical structure doses.

Methods And Materials: The plans of patients with uveal melanoma treated consecutively with eye plaque brachytherapy at a single institution from January 2016 to December 2017 were reviewed. Both a COMS plan and an EP plan using plaques of the same shape were generated for each patient using the Isoaid Plaque Simulator software such that >90% of the tumor + 2 mm margin received 85 Gy over 72 hours from iodine-125 sources. Dose statistics were recorded and analyzed using standard statistical methods.

Results: Plans from a total of 62 patients were analyzed. The mean tumor volume was 0.46 cm (range: 0.02-2.02), and tumors were located on average 5.89 mm (range: 0-15.0) from the macula and 6.25 mm (range: 0-16.0) from the optic disc. All plans met the treatment planning criteria for tumor coverage and were optimized to reduce dose to the adjacent organs at risk. There were no significant differences in the mean doses to the fovea (mean difference [MD] = -0.87 Gy; 95% confidence interval [CI]: -4.90 to 3.16; p = 0.80), macula (MD = -1.02 Gy; 95% CI: -4.15 to 2.11; p = 0.65), or optic disc (MD = 1.07 Gy; 95% CI: -0.77 to 2.91; p = 0.34) between the COMS and circular EP plaques.

Conclusions: Overall, neither the COMS plaques nor the circular EP plaques provided consistently superior dosimetry for the treatment of uveal melanoma. The choice of plaque may be based on other considerations such as cost and surgeon preference.
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http://dx.doi.org/10.1016/j.brachy.2019.01.005DOI Listing
December 2019

Diagnosis of Bilateral Retinocytoma in an Adolescent Patient Using Multimodal Imaging and Genetic Testing.

Ophthalmic Surg Lasers Imaging Retina 2018 10;49(10):812-814

A 12-year-old male presented for evaluation of asymptomatic bilateral retinal tumors. Both eyes contained whitish-gray retinal tumors with intralesional calcifications. Enhanced depth optical coherence tomography and high-resolution (20 MHz) ultrasonography narrowed the differentiation diagnosis to astrocytic hamartoma versus retinocytoma. Genetic testing of a saliva sample was negative for tuberous sclerosis complex but positive for a novel mutation in the retinoblastoma gene (RB1). Taken together, these findings were consistent with a diagnosis of bilateral retinocytoma in a patient with germline RB1 mutation. This case demonstrates the importance of combining clinical imaging and genetic testing in the evaluation of bilateral intraocular tumors. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:812-814.].
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http://dx.doi.org/10.3928/23258160-20181002-11DOI Listing
October 2018

Are Risk Factors for Growth of Choroidal Nevi Associated With Malignant Transformation? Assessment With a Validated Genomic Biomarker.

Am J Ophthalmol 2019 01 7;197:168-179. Epub 2018 Sep 7.

Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA.

Purpose: To test the hypothesis that widely used clinical risk factors for growth of choroidal nevi are associated with malignant transformation.

Methods: Fine needle biopsy for assignment of gene expression profile (class 1 or class 2) was performed in 207 choroidal melanocytic tumors < 3.5 mm in thickness. The class 2 profile was employed as a validated biomarker for malignant transformation. The following data were collected: patient age and sex, tumor diameter and thickness, distance of posterior tumor margin from the optic disc, and the presence or absence of serous retinal detachment, orange lipofuscin pigment, drusen, retinal pigment epithelial fibrosis, retinal pigment epithelial atrophy, visual symptoms, and documented tumor growth.

Results: Clinical features associated with the class 2 profile included patient age > 60 years and tumor thickness > 2.25 mm (Fisher exact test, P = .002 for both). Documented growth was not associated with the class 2 profile (P = .5). The odds ratio of a tumor having the class 2 profile was 2.8 (95% confidence interval 1.3-5.9) for patient age > 60 years and 3.5 (95% confidence interval 1.4-8.8) for tumor thickness > 2.25 mm. For patients with both risk factors, the "number needed to treat" to identify 1 patient with a class 2 tumor was 4.3 (P = .0002). No other clinical feature or combination of features was associated with the class 2 profile.

Conclusions: None of the widely used choroidal nevus risk factors for tumor growth, nor documented growth itself, is pathognomonic of malignant transformation as defined by class 2 gene expression profile. Patient age and tumor thickness may be helpful for identifying small choroidal melanocytic tumors that are more likely to have the class 2 profile. Observation for growth prior to treatment continues to be reasonable for most patients with suspicious choroidal nevi. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
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http://dx.doi.org/10.1016/j.ajo.2018.08.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291343PMC
January 2019

Gene Expression Profiling and PRAME Status Versus Tumor-Node-Metastasis Staging for Prognostication in Uveal Melanoma.

Am J Ophthalmol 2018 11 6;195:154-160. Epub 2018 Aug 6.

Ocular Oncology Service, Bascom Palmer Eye Institute and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA. Electronic address:

Purpose: To compare the prognostic accuracy of gene expression profiling (GEP) combined with PRAME status vs the clinical Tumor-Node-Metastasis (TNM) staging in patients with uveal melanoma (UM).

Design: Retrospective cohort study.

Methods: The study included 240 consecutive patients with UM. Tumors were assessed for GEP status (Class 1 or Class 2) using a validated 15-gene assay and PRAME expression status using quantitative polymerase chain reaction. TNM staging was according to the American Joint Committee on Cancer 8th edition. Statistical analysis included univariate and multivariate Cox proportional hazard models. Metastasis was the primary endpoint.

Results: GEP was Class 1 in 128 (53.3%) cases and Class 2 in 112 (46.7%) cases. PRAME status was negative in 157 (65.4%) cases and positive in 83 (34.6%) cases. TNM was stage I in 26 (10.8%) cases, IIA in 67 (27.9%) cases, IIB in 50 (20.8%) cases, IIIA in 59 (24.6%) cases, and IIIB in 38 (15.8%) cases. Metastatic disease was detected in 59 (24.6%) cases after median follow-up of 29 months (mean 42 months; range 1-195 months). Variables associated with metastasis included (in order of decreasing significance): GEP class (P = 1.5 × 10), largest basal tumor diameter (P = 2.5 × 10), PRAME status (P = 2.6 × 10), and TNM stage (P = 3.7 × 10). The prognostic accuracy of an optimized 3-category GEP/PRAME model (P = 8.6 × 10) was superior to an optimized TNM model (P = 1.3 × 10).

Conclusions: In UM, molecular prognostic testing using GEP and PRAME provides prognostic accuracy that is superior to TNM staging.
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http://dx.doi.org/10.1016/j.ajo.2018.07.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214741PMC
November 2018

BILATERAL INTRAVITREAL 0.19-MG FLUOCINOLONE ACETONIDE IMPLANT FOR PERSISTENT NONDIABETIC CYSTOID MACULAR EDEMA AFTER VITRECTOMY.

Retin Cases Brief Rep 2021 May;15(3):261-265

Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina.

Background/purpose: Iluvien (Alimera Science, Alpharetta, GA) is an injectable, nonbiodegradable, sustained-release 0.19-mg fluocinolone acetonide intravitreal implant. Although currently approved by the Food and Drug Administration only for diabetic macular edema previously treated with a course of corticosteroids without a clinically significant intraocular pressure response, the 0.19-mg fluocinolone acetonide implant could theoretically be used to treat other noninfectious inflammatory conditions including persistent cystoid macular edema because of nondiabetic etiologies.

Methods: Interventional case report. A 79-year-old man had persistent cystoid macular edema after pars plana vitrectomy in both eyes that was refractory to topical treatments and intravitreal anti-vascular endothelial growth factor. His cystoid macular edema was responsive to preservative-free intravitreal triamcinolone acetonide after which he developed noninfectious endophthalmitis or pseudoendophthalmitis in both eyes precluding further intravitreal triamcinolone acetonide injections. He was subsequently treated with bilateral intravitreal 0.19-mg fluocinolone acetonide implants.

Results: At the most recent post-treatment follow-up (11 months for the right eye and 13 months for the left eye), the patient demonstrated an improvement in visual acuity, 20/126 to 20/50 in the right eye and 20/80 to 20/40 in the left eye, and in central subfield thickness, 592 μm to 288 μm in the right eye and 565 μm to 287 μm in the left eye, without intraocular pressure elevation.

Conclusion: The intravitreal 0.19-mg fluocinolone acetonide implant is an effective and potentially safe off-label therapeutic option for persistent nondiabetic cystoid macular edema after vitrectomy.
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http://dx.doi.org/10.1097/ICB.0000000000000779DOI Listing
May 2021

Optic Nerve Swelling in a Patient With Cancer.

JAMA Ophthalmol 2018 10;136(10):1195-1196

Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.

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http://dx.doi.org/10.1001/jamaophthalmol.2018.0163DOI Listing
October 2018

A Frag Bag for Efficient Removal of Dislocated Nuclear Material.

Ophthalmic Surg Lasers Imaging Retina 2017 12;48(12):1006-1008

Dislocated nuclear material may be present in the vitreous cavity following complicated cataract surgery, closed globe injury, or spontaneous dislocation of the crystalline lens. The authors report herein a method to remove larger pieces of retained nuclear material during vitrectomy surgery with a retractable basket made from nitinol referred to as the "Frag Bag" (patent pending). Although originally designed for cystoscopic removal of kidney stones, this instrument fits easily through a 23-gauge vitrectomy port. The basket allows for retrieval of larger pieces of retained nuclear material with stabilization of the lens material in the mid-vitreous cavity and softening of the nuclear material to allow efficient and safe removal with the vitreous cutter, away from the retinal surface. Use of the Frag Bag may potentially improve the safety and efficiency of a pars plana lensectomy by obviating the need for a phacofragmatome and decreasing the number of times instruments are brought close to the retinal surface. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:1006-1008.].
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http://dx.doi.org/10.3928/23258160-20171130-08DOI Listing
December 2017

Venous Loop Reveals an Occult Retinoblastoma Tumor.

Ophthalmic Surg Lasers Imaging Retina 2017 09;48(9):768-770

A 14-day-old girl presented with bilateral hereditary retinoblastoma. At 3 months, a slight bend in the superotemporal arcade was observed to have developed into a venous loop. With concern for an occult lesion along the arcade, handheld optical coherence tomography (hhOCT) confirmed a small tumor and helped to guide prompt laser treatment while sparing the venous arcade. A venous loop is a previously unrecognized clinical finding that preceded the clinical detection and hhOCT confirmation of the tumor. The authors hypothesize that the venous loop was induced by pro-angiogenic factors secreted by the tumor. Portable hhOCT is a valuable adjunct imaging modality in the diagnosis and management of small retinoblastoma tumors. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:768-770.].
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http://dx.doi.org/10.3928/23258160-20170829-14DOI Listing
September 2017

Neuro-oculo-cutaneous cavernous hemangiomas: a CCM1 mutation-associated phakomatosis.

J AAPOS 2017 Oct 1;21(5):426-429.e1. Epub 2017 Sep 1.

Department of Ophthalmology, Duke University, Durham, North Carolina; Department of Radiation Oncology, Duke University, Durham, North Carolina; Department of Ophthalmology, Stanford University, Stanford, California. Electronic address:

Evaluation for intracranial lesions in a patient with retinal cavernous hemangiomas is vital for early recognition of this heritable and potentially life-threatening disease. We report a case of a highly penetrant but variably expressed form of cerebral cavernous malformation syndrome with cerebral, cutaneous, and retinal cavernomas in a family found to harbor a nonsense mutation of the CCM1 gene.
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http://dx.doi.org/10.1016/j.jaapos.2017.06.012DOI Listing
October 2017

A Woman With a Spot in Her Vision.

JAMA Ophthalmol 2017 09;135(9):997-998

Department of Ophthalmology, Duke University, Durham, North Carolina.

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http://dx.doi.org/10.1001/jamaophthalmol.2017.0426DOI Listing
September 2017

Anterior Chamber Angle Invasion of Iridociliary Melanoma.

Ophthalmology 2017 06;124(6):842

Department of Ophthalmology, Duke University, Durham, North Carolina.

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http://dx.doi.org/10.1016/j.ophtha.2016.12.003DOI Listing
June 2017

Pigmented Iridociliary Lesion and Increased Intraocular Pressure.

JAMA Ophthalmol 2017 07;135(7):805-806

Department of Ophthalmology, Duke University, Durham, North Carolina3Byers Eye Institute, Stanford University, Palo Alto, California.

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http://dx.doi.org/10.1001/jamaophthalmol.2016.5128DOI Listing
July 2017

Ocular Surface Epithelial Atypia Mimicking Squamous Neoplasia in Association With Ulcerative Colitis.

Cornea 2017 Apr;36(4):502-505

Departments of *Ophthalmology; †Pathology; and ‡Radiation Oncology, Duke University Medical Center, Durham, NC; and §Department of Ophthalmology, Stanford University Medical Center, Palo Alto, CA.

Purpose: Inflammatory bowel disease may be associated with extraintestinal manifestations. We report a case of severe reactive epithelial atypia resembling ocular surface squamous neoplasia (OSSN) in a patient with ulcerative colitis (UC).

Methods: Case report.

Results: A 32-year-old woman presented with sequential, progressive keratoconjunctival lesions in the left and right eyes, and both lesions were excised. Anterior segment optical coherence tomography demonstrated features similar to OSSN, whereas histological examination revealed severe reactive epithelial atypia mimicking severe dysplasia. Shortly after treatment of the second eye, the patient was diagnosed with UC. Residual disease improved dramatically in response to systemic corticosteroids.

Conclusions: Severe ocular surface epithelial atypia resembling OSSN may be seen in association with UC.
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http://dx.doi.org/10.1097/ICO.0000000000001144DOI Listing
April 2017

Bilateral Prefoveal Sub-Internal Limiting Membrane Hemorrhage in Autoimmune Hemolytic Anemia.

Ophthalmic Surg Lasers Imaging Retina 2016 12;47(12):1151-1153

Severe anemia can cause multilayered retinal hemorrhages. A 65-year-old woman noted "red spheres" in the central vision of both eyes during a hospital admission for autoimmune hemolytic anemia. Examination revealed extensive multilayered retinal hemorrhages, including bilateral foveal preretinal hemorrhage. Spectral-domain optical coherence tomography localized the preretinal blood to the sub-internal limiting membrane (ILM) space. Various options are available for management of such hemorrhage, including observation for spontaneous resolution, YAG laser membranotomy, or pars plana vitrectomy with ILM peeling. In the authors' patient, the size of the sub-ILM hemorrhage spontaneously improved during the course of 1 month, with both subjective and objective visual improvement. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1151-1153.].
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http://dx.doi.org/10.3928/23258160-20161130-11DOI Listing
December 2016

ω-3 Tear Film Lipids Correlate With Clinical Measures of Dry Eye.

Invest Ophthalmol Vis Sci 2016 05;57(6):2472-8

Bascom Palmer Eye Institute, Department of Opthamology, University of Miami, Miami, Florida, United States 3Department of Surgical Services, Miami Veterans Administration Medical Center, Miami, Florida, United States.

Purpose: ω-3 and ω-6 polyunsaturated fatty acids modulate inflammatory processes throughout the body through distinct classes of lipid mediators that possess both proinflammatory and proresolving properties. The purpose of this cross-sectional study was to explore the relationship between lipid profiles in human tears and dry eye (DE) symptoms and signs.

Methods: Forty-one patients with normal eyelid and corneal anatomy were prospectively recruited from a Veterans Administration Hospital over 18 months. Symptoms and signs of DE were assessed, and tear samples was analyzed by mass spectrometry-based lipidomics. Statistical analyses comparing the relationship between tear film lipids and DE included Pearson/Spearman correlations and t-tests.

Results: Arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were present in more than 90% of tear film samples. The ratio of ω-6 (AA) to ω-3 (DHA+EPA) fatty acids was correlated with multiple measures of tear film dysfunction (tear breakup time, Schirmer 2 scores, and corneal staining; all P < 0.05). Arachidonic acid-derived prostaglandin E2 was detected in the majority of samples and correlated with low tear osmolarity, meibomian gland plugging, and corneal staining.

Conclusions: Both ω-3 and ω-6 lipid circuits are activated in the human tear film. The ratio of ω-6:ω-3 tear lipids is elevated in DE patients in proportion to the degree of tear film dysfunction and corneal staining. Metabolic deficiency of ω-3 tear film lipids may be a driver of chronic ocular surface inflammation in DE.
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http://dx.doi.org/10.1167/iovs.16-19131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857833PMC
May 2016

Prognostic Implications of Tumor Diameter in Association With Gene Expression Profile for Uveal Melanoma.

JAMA Ophthalmol 2016 Jul;134(7):734-40

Ocular Oncology Service, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida2Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.

Importance: Uveal melanoma (UM) can be divided into prognostically significant subgroups based on a prospectively validated and widely used 15-gene expression profile (GEP) test. Class 1 UMs have a low risk and class 2 UMs have a high risk for metastasis.

Objective: To determine whether any clinicopathologic factors provide independent prognostic information that may enhance the accuracy of the GEP classification.

Design, Setting, And Participants: This retrospective observational study performed at 2 ocular oncology referral centers included 339 patients in a primary cohort and 241 patients in a validation cohort. Both cohorts had a diagnosis of UM arising from the ciliary body and/or choroid. All patients underwent tumor biopsy for GEP prognostic testing. Clinicopathologic variables included patient age and sex, tumor thickness, largest basal tumor diameter (LBD), ciliary body involvement, and pathologic cell type. Patients from the primary cohort were enrolled from November 1, 1998, to March 16, 2012; from the validation cohort, from November 4, 1996, to November 7, 2013. Follow-up for the primary cohort was completed on August 18, 2013; for the validation cohort, December 10, 2013. Data were analyzed from November 12, 2013, to November 25, 2015.

Main Outcome And Measures: Progression-free survival (PFS). The secondary outcome was overall survival.

Results: The primary cohort included 339 patients (175 women [51.6%]; mean [SD] age, 61.8 [13.6] years). The most significant prognostic factor was GEP classification (exp[b], 10.33; 95% CI, 4.30-24.84; P < .001). The only other variable that provided independent prognostic information was LBD (exp[b], 1.13; 95% CI, 1.02-1.26; P = .02). Among class 2 UMs, LBD showed a modest but significant association with PFS (exp[b], 1.13; 95% CI, 1.04-1.24; P = .005). The 5-year actuarial metastasis-free survival estimates (SE) were 97% (3%) for class 1 UMs with LBD of less than 12 mm, 90% (4%) for class 1 UMs with LBD of at least 12 mm, 90% (9%) for class 2 UMs with LBD of less than 12 mm, and 30% (7%) for class 2 UMs with LBDs of at least 12 mm. The independent prognostic value of LBD and the 12-mm LBD cutoff were corroborated in the independent validation 241-patient cohort.

Conclusions And Relevance: Class 2 UMs had better prognosis when the LBD was less than 12 mm at the time of treatment. These findings could have important implications for patient counseling, primary tumor treatment, clinical trial enrollment, metastatic surveillance, and adjuvant therapy.
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http://dx.doi.org/10.1001/jamaophthalmol.2016.0913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966166PMC
July 2016

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY DOCUMENTATION OF MACULAR PSEUDOHOLE EVOLUTION AND SPONTANEOUS RESOLUTION.

Retin Cases Brief Rep 2016 ;10(4):377-81

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida.

Purpose: To describe the natural history, optical coherence tomography characteristics, and proposed biomechanics of macular pseudohole (MPH) evolution and spontaneous resolution.

Methods: Clinical case report, with longitudinal follow-up documented by fundus photographs and spectral domain optical coherence tomography.

Results: A 26-year-old woman presented with visual disturbance secondary to an idiopathic epiretinal membrane. Subsequent formation of an MPH was observed. Spontaneous peeling of the epiretinal membrane occurred in conjunction with posterior vitreous detachment 6.5 years after initial presentation. The MPH resolved, and the patient's vision improved.

Conclusion: Spontaneous epiretinal membrane peeling represents a potential mechanism for visual and anatomical improvement in eyes with MPH. This is the first published observation of MPH resolution documented by spectral domain optical coherence tomography.
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http://dx.doi.org/10.1097/ICB.0000000000000268DOI Listing
March 2017

Dry eye symptom severity and persistence are associated with symptoms of neuropathic pain.

Br J Ophthalmol 2015 May 21;99(5):665-8. Epub 2014 Oct 21.

Miami Veterans Administration Medical Center, Miami, Florida, USA John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami, Florida, USA.

Objective: Studies of patients with non-ocular pain suggest that it is therapeutically useful to identify those with features of neuropathic pain. No data is available, however, on whether this approach has similar utility in dry eye. The purpose of this study was to determine whether severity and persistence of dry eye symptoms associate with self-reported symptoms of neuropathic ocular pain (NOP).

Methods:

Design: Cohort study.

Participants/setting: 102 men seen in the Miami Veterans Affairs eye clinic. A baseline evaluation was performed consisting of the dry eye questionnaire 5 (DEQ5) and ocular surface evaluation. Patients were contacted ≥2 years later to repeat the DEQ5 and complete questionnaires that further characterised their eye pain.

Main Outcome Measure: The relationship between dry eye symptom severity and persistence (DEQ5) and additional measures of ocular pain (NOP).

Results: Of 102 patients with variable dry eye symptoms, 70 reported at least mild symptoms on both encounters (DEQ5≥6). Fifty-four of 70 (77%) reported ≥1 NOP feature, and the number of NOP features correlated moderately with dry eye symptoms at both encounters (r=0.31-0.46, p<0.01). Patients with any symptom of NOP had higher dry eye symptom scores at both encounters (p<0.05), but similar ocular surface parameters. Hypersensitivity to wind and photoallodynia were associated with having mild or greater symptoms on both encounters (OR 3.4, 95% CI 1.2 to 10.0, p=0.02; OR 15.6, 95% CI 2.0 to 123, p=0.009, respectively).

Conclusions: NOP features are common in patients with symptomatic dry eye and these features correlate with symptom severity and persistence.
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http://dx.doi.org/10.1136/bjophthalmol-2014-306057DOI Listing
May 2015

Ganglion cell loss in relation to visual disability in multiple sclerosis.

Ophthalmology 2012 Jun 23;119(6):1250-7. Epub 2012 Feb 23.

Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

Purpose: We used high-resolution spectral-domain optical coherence tomography (SD-OCT) with retinal segmentation to determine how ganglion cell loss relates to history of acute optic neuritis (ON), retinal nerve fiber layer (RNFL) thinning, visual function, and vision-related quality of life (QOL) in multiple sclerosis (MS).

Design: Cross-sectional study.

Participants: A convenience sample of patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes). Among MS eyes, 87 had a history of ON before enrollment.

Methods: The SD-OCT images were captured using Macular Cube (200×200 or 512×128) and ONH Cube 200×200 protocols. Retinal layer segmentation was performed using algorithms established for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus control eyes and MS ON versus non-ON eyes. The relation between changes in macular thickness and visual disability was also examined.

Main Outcome Measures: The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement composite score.

Results: Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (P<0.001 and P = 0.001) and in MS ON versus non-ON eyes (P<0.001 for both measures). Peripapillary RNFL, macular RNFL, GCL+IPL, and the combination of macular RNFL+GCL+IPL were significantly correlated with VA (P≤0.001), 2.5% LCLA (P<0.001), and 1.25% LCLA (P≤0.001). Among OCT measurements, reductions in GCL+IPL (P<0.001), macular RNFL (P = 0.006), and the combination (macular RNFL+GCL+IPL; P<0.001) were most strongly associated with lower (worse) NEI-VFQ-25 and 10-Item Supplement QOL scores; GCL+IPL thinning was significant even accounting for macular RNFL thickness (P = 0.03 for GCL+IPL, P = 0.39 for macular RNFL).

Conclusions: We demonstrated that GCL+IPL thinning is most significantly correlated with both visual function and vision-specific QOL in MS, and may serve as a useful structural marker of disease. Our findings parallel those of magnetic resonance imaging studies that show gray matter disease is a marker of neurologic disability in MS.

Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
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http://dx.doi.org/10.1016/j.ophtha.2011.11.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631566PMC
June 2012