Publications by authors named "Kunal Malik"

37 Publications

Stalagmite iridopathy.

Indian J Ophthalmol 2021 Aug;69(8):1993

Wills Eye Hospital, Philadelphia, PA, USA.

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http://dx.doi.org/10.4103/ijo.IJO_2619_20DOI Listing
August 2021

Surgical instrument disinfection during the era of COVID-19.

Dermatol Online J 2021 Feb 15;27(2). Epub 2021 Feb 15.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.

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February 2021

Lens capsule rupture in a nonaccidental trauma.

Can J Ophthalmol 2021 Jan 23. Epub 2021 Jan 23.

Eye Pathology Laboratory, University of Wisconsin, School of Medicine and Public Health, Madison, Wisc.

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http://dx.doi.org/10.1016/j.jcjo.2020.12.019DOI Listing
January 2021

Full scalp hair regrowth in a 4-year-old girl with alopecia areata and atopic dermatitis treated with dupilumab.

JAAD Case Rep 2020 Dec 15;6(12):1286-1287. Epub 2020 Oct 15.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.

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http://dx.doi.org/10.1016/j.jdcr.2020.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701016PMC
December 2020

Patient education in Mohs surgery: a review and critical evaluation of techniques.

Arch Dermatol Res 2021 May 12;313(4):217-224. Epub 2020 Aug 12.

Department of Dermatology, SUNY Downstate, Brooklyn, New York, USA.

Background: Traditional in-person discussion alone is often used for preoperative education in Mohs micrographic surgery (MMS). The appropriate use of more modern education techniques is not well defined in the MMS literature.

Objective: The authors aim to evaluate patient education techniques for MMS, address education in special populations, and highlight opportunities for improvement.

Methods And Materials: We performed a PubMed literature search with keywords "Mohs" and "education", "teaching", "understanding", "explanation", "preoperative", or "consent" with no restriction on publication time frame due to literature scarcity.

Results: Teledermatology consultation, MMS videos, 3D models, pamphlets/online materials, and shared medical appointments appear to be effective techniques (GRADE B). Analogies are also anecdotally helpful when integrated into traditional verbal education (GRADE C). The role of preoperative educational phone calls is more controversial (GRADE C).

Conclusion: Regardless of the education technique utilized, no singular technique entirely replaces the traditional in-person discussion. Having access to multiple modalities can be beneficial for patients, allowing them options to choose their preferred method(s) of education. MMS is a difficult topic to conceptualize, and further research into educational techniques is needed to provide clear guidelines for Mohs surgeons.
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http://dx.doi.org/10.1007/s00403-020-02119-5DOI Listing
May 2021

Synthetic cannabinoid induced ocular self-injury.

Orbit 2021 Aug 18;40(4):326-328. Epub 2020 Jun 18.

Department of Ophthalmology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA.

Synthetic cannabinoids are a relatively new and increasingly popular recreational drug. While used for their hallucinogenic properties similar to natural cannabis, they have a greater and more serious side effect profile, including potentially severe neuropsychiatric toxicity. We report the cases of two patients with untreated schizophrenia who presented after ocular self-injury while intoxicated on K2. Both patients hallucinated that a bug was behind their eye, and in their attempts at removing the bug, damaged the periocular soft tissue. To our knowledge these are the first reports of ocular self-injury from synthetic cannabinoid intoxication.
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http://dx.doi.org/10.1080/01676830.2020.1781199DOI Listing
August 2021

Escaping a hairy situation: The pencil bun technique.

J Am Acad Dermatol 2020 Jun 1. Epub 2020 Jun 1.

Veterans Affairs Medical Center, Brooklyn, New York; Department of Dermatology, State University of New York Downstate, Brooklyn, New York. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.05.107DOI Listing
June 2020

Back to the basics: Diluted bleach for COVID-19.

J Am Acad Dermatol 2020 07 10;83(1):279-280. Epub 2020 Apr 10.

Veterans Affairs Medical Center, Brooklyn, New York; Department of Dermatology, State University of New York Downstate, Brooklyn, New York. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.04.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151288PMC
July 2020

UVEAL METASTASIS BASED ON PATIENT AGE IN 1,111 PATIENTS: Comparison of Clinical Features and Outcomes Per Age Category.

Retina 2020 Feb;40(2):204-213

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: To evaluate clinical features and survival outcomes of uveal metastasis based on patient age.

Methods: Retrospective analysis of all patients with uveal metastasis evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA, USA between February 1, 1974 and June 1, 2017. The features and outcomes were analyzed based on patient age classified as children (0-20 years), young adults (21-40 years), middle [aged] adults (41-60 years), older adults (61-80 years) and senior adults (81-100 years).

Results: There were 1111 consecutive patients, including children (n = 3, <1%), young adults (n = 77, 7%), middle adults (n = 472, 42%), older adults (n = 509, 46%), and senior adults (n = 50, 4%). At uveal metastasis diagnosis, demographics included mean patient age of 60 years, Caucasian race (88%), and female gender (64%). Compared to the largest cohort (older adults), there were significant differences (age group versus [vs.] older adults) in Caucasian race (senior adult 98% vs. 89%, p = 0.042), male sex (young adults: 22% vs. 43%, p < 0.001) (middle adults: 29% vs. 43%, p < 0.001), unilateral tumor (young adult: 70% vs. 86%, p < 0.001) (middle adult: 79% vs. 86%, p = 0.003) (senior adults: 96% vs. 86%, p = 0.045), and cancer origin in breast (young adults: 51% vs. 32%, p = 0.002) (middle adults: 44% vs 32%, p < 0.001), lung (young adults: 14% vs. 30%, p = 0.004), kidney (young adults: 0% vs. 5%, p = 0.043), prostate (middle adults: 1% vs. 4%, p = 0.001), gastrointestinal tract (senior adults: 8% vs. 2%, p = 0.028), and others (children: 100% vs. 4%, p < 0.001) (young adults: 10% vs. 4%, p = 0.044). Kaplan-Meier survival (children, young, middle, older, and senior adults) at 1 year was 33%, 48%, 60%, 62%, and 76% and at 5 years was 0%, 22%, 29%, 25%, and 40%, respectively, with no difference per age category. The mean overall survival was 17.2 months and children demonstrated hazard ratio (HR) for death at 1 year of 2.1 relative to older adults.

Conclusion: Uveal metastasis is found in all age groups. Compared to older adults, primary cancer site was more often breast and less likely lung in young and middle adults. Other rare sites were more often seen in children. Survival outcomes at 1 and 5 years were most favorable for senior adults and least favorable for children.
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http://dx.doi.org/10.1097/IAE.0000000000002364DOI Listing
February 2020

Philadelphia glaucoma detection and treatment project: ocular outcomes and adherence to follow-up at a single health centre.

Can J Ophthalmol 2019 12 19;54(6):717-722. Epub 2019 Sep 19.

Wills Eye Hospital, Glaucoma Research Center, Philadelphia, PA; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA.

Objectives: To determine ocular outcomes and factors associated with adherence to ophthalmic follow-up in a medically underserved population at a single health centre in Philadelphia.

Design: Retrospective chart review.

Participants: Patients from a community glaucoma screening program.

Methods: Chart review was conducted for participants who received a complete eye examination at the Philadelphia District Health Center 5 between January 1, 2012 and May 31, 2014 within the Philadelphia Glaucoma Detection and Treatment Project. Multivariate logistic regression was used to determine factors related to ophthalmic follow-up adherence.

Results: A total of 249 participants completed an eye examination (mean age = 57.7 ± 6.9 years). Most were African American (n = 220; 88.4%); female (n = 129; 51.8%). Forty-seven participants (18.9%) received glaucoma-related diagnoses, 20 (8.0%) were prescribed ocular medication, and 26 (10.4%) underwent laser therapy. Ninety (36.1%) attended their recommended follow-up eye examination at the health centre. Glaucoma-related diagnosis (p ≤ 0.001), recommendation of a 4- to 6-week follow-up period (p < 0.001), prescribed eye drops (p < 0.001), or received laser therapy (p = 0.047) were factors most predictive of ophthalmic follow-up adherence.

Conclusions: The collaborative effort of eye care providers and health centres offers an important opportunity to detect, treat, and manage glaucoma and other ocular pathology in medically underserved communities. Having a glaucoma-related diagnosis, initiating treatment, and scheduling regular follow-up visits are the most important factors influencing adherence to follow-up eye appointments.
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http://dx.doi.org/10.1016/j.jcjo.2019.03.003DOI Listing
December 2019

Uveal metastasis in 1111 patients: Interval to metastasis and overall survival based on timing of primary cancer diagnosis.

Saudi J Ophthalmol 2019 Jul-Sep;33(3):229-237. Epub 2019 Jul 25.

The Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, United States.

Purpose: To evaluate interval between primary cancer diagnosis and uveal metastasis and assess survival outcomes based on whether the primary cancer was diagnosed before or after uveal metastasis.

Methods: In this retrospective analysis, all patients with uveal metastasis evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA, USA between February 1, 1974 and June 1, 2017 were included. Features and outcomes based on timing of primary cancer diagnosis, whether before or after diagnosis of uveal metastasis, were assessed.

Results: A total of 2214 uveal metastases were diagnosed in 1310 eyes of 1111 consecutive patients. Primary cancer was known prior to uveal metastasis in 742 patients (67%) and not known in 369 (33%). Of those not known, the primary cancer was later found in 192 patients (17%) and never found in 177 patients (16%). For those with known primary cancer, mean interval from primary cancer diagnosis to uveal metastasis was 5.2 years with differences in primary sites of gastrointestinal (2.1 years, p = 0.003), lung (2.2 years, p < 0.001), breast (6.5 years, p < 0.001), and thyroid (13 years, p < 0.001). By Kaplan-Meier analysis, the 5-year overall survival showed no difference between patients with primary cancer found before (28%) vs after (20%) vs never found (33%), relative to uveal metastasis.

Conclusion: Of 1111 patients with uveal metastasis, early-onset uveal metastases were found with lung and gastrointestinal tract cancers, whereas late-onset metastases were found with breast and thyroid cancers. Overall survival did not vary on whether the primary tumor was diagnosed before, after, or never found, relative to uveal metastasis.
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http://dx.doi.org/10.1016/j.sjopt.2019.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819751PMC
July 2019

Uveal Metastasis Based on Patient Sex in 2214 Tumors of 1111 Patients. A Comparison of Female Versus Male Clinical Features and Outcomes.

Asia Pac J Ophthalmol (Phila) 2019 Jul-Aug;8(4):298-303

Wills Eye Hospital, Ocular Oncology Service, Thomas Jefferson University, Philadelphia, PA.

Background: Lacking in previous studies on uveal metastasis is a robust statistical comparison of patient demographics, tumor features, and overall survival based on patient sex.

Objective: The aim of this study was to evaluate demographics, clinical features, and overall survival of patients with uveal metastasis based on sex.

Method: This is a retrospective analysis. All patients were evaluated on the Ocular Oncology Service, Wills Eye Hospital, PA between January 1, 1974 and June 1, 2017.

Results: A total of 2214 uveal metastases were diagnosed in 1310 eyes of 1111 consecutive patients. A comparison (female versus male) revealed differences across several demographic and clinical features including, among others, mean age at metastasis diagnosis (58 vs 63 years, P < 0.001), bilateral disease (21% vs 11%, P < 0.001), and mean number of metastases per eye (1.8 vs 1.6 tumors per eye, P = 0.04). There were differences in overall mean survival (20 vs 13 months, P = 0.03) and 5-year survival (Kaplan-Meier estimate) (31% vs 21%, P < 0.001).

Conclusions: There are demographic, clinical, and survival differences when patients with uveal metastases are compared by sex. Understanding these differences can aid the clinician in better anticipating patient outcomes.
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http://dx.doi.org/10.1097/APO.0000000000000247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727921PMC
August 2019

Choroidal amelanotic tumours: clinical differentiation of benign from malignant lesions in 5586 cases.

Br J Ophthalmol 2020 02 25;104(2):194-201. Epub 2019 Apr 25.

Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA

Purpose: To investigate demographics and clinical features of patients with amelanotic choroidal tumours.

Design: Retrospective analysis.

Methods: Comparison of demographic and clinical features of various amelanotic choroidal tumours based on stratification by patient age, sex and tumour diameter. Included were all patients with amelanotic choroidal tumours evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA, over a 45-year time period.

Results: A total of 5586 amelanotic choroidal tumours in 4638 eyes of 4441 patients were included with a mean age at presentation of 58 years (median 60, range 0.1-100 years). Most patients were white (95%), female (56%) and with unilateral lesion (96%). By comparison, amelanotic melanoma presented at a younger mean age (57 years) compared with metastasis (60 years, p<0.001), nevus (61 years, p<0.001), lymphoma (65 years, p<0.001), sclerochoroidal calcification (70 years, p<0.001) and peripheral exudative haemorrhagic chorioretinopathy (80 years, p<0.001). Melanoma presented at an older mean age compared with osteoma (30 years, p<0.001), granuloma (42 years, p<0.001), haemangioma (49 years, p<0.001) and inflammatory choroidal lesions (49 years, p<0.001). Differences in race and sex were also seen between the various amelanotic choroidal lesions. With few exceptions, amelanotic melanoma had significantly larger basal diameter, greater thickness, more frequent association with subretinal fluid and more often ultrasonographically hollow, compared with other amelanotic choroidal lesions.

Conclusion: Understanding the demographic and clinical features of amelanotic choroidal melanoma and other amelanotic lesions could lead to an earlier and more accurate diagnosis.
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http://dx.doi.org/10.1136/bjophthalmol-2018-313680DOI Listing
February 2020

The blood proteomic signature of early-onset pediatric atopic dermatitis shows systemic inflammation and is distinct from adult long-standing disease.

J Am Acad Dermatol 2019 Aug 19;81(2):510-519. Epub 2019 Apr 19.

Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address:

Background: Despite increasing evidence that adults with long-standing atopic dermatitis (AD) have systemic inflammation, little is known about systemic inflammation in recent-onset early pediatric AD.

Objective: To analyze blood inflammatory proteins of early pediatric AD.

Methods: Using high-throughput proteomics (proximity extension assay), we assessed 257 inflammatory and cardiovascular risk proteins in the blood of 30 children with moderate to severe AD younger than 5 years of age (within 6 months of onset) compared with age-matched pediatric control individuals and adult patients with AD.

Results: In pediatric AD blood, T helper (Th) type 2 (CCL13, CCL22) and Th17 (peptidase inhibitor-3/elafin) markers were increased, together with markers of tissue remodeling (matrix metalloproteinases 3/9/10, urokinase receptor), endothelial activation (E-selectin), T-cell activation (IL2RA), neutrophil activation (myeloperoxidase), lipid metabolism (FABP4), and growth factors (FGF21, transforming growth factor-α). Total numbers of dysregulated proteins were smaller in pediatric AD (n = 22) than in adult AD (n = 61). Clinical severity scores were positively correlated with receptors for interleukins 33 and 36 and inversely correlated with some Th1 markers (interferon gamma, CXCL11).

Limitations: Different baseline expression levels in healthy pediatric vs adult samples.

Conclusions: Within months of pediatric AD onset, systemic immune activation is present, with Th2/Th17 skewing but otherwise different proteomic patterns from adult AD. Future correlation of proteomic patterns with disease course, comorbidity development, and drug response may yield predictive biomarkers.
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http://dx.doi.org/10.1016/j.jaad.2019.04.036DOI Listing
August 2019

Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis.

J Allergy Clin Immunol 2019 07 24;144(1):144-156. Epub 2019 Jan 24.

Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: Atopic dermatitis (AD) shows differential clinical presentation in older compared with younger patients. Nevertheless, changes in the AD molecular profile with age are unknown.

Objective: We sought to characterize age-related changes in the AD profile.

Methods: We evaluated age-specific changes in lesional and nonlesional tissues and blood from patients with moderate-to-severe AD (n = 246) and age-matched control subjects (n = 71) using immunohistochemistry, quantitative real-time PCR, and Singulex in a cross-sectional study. Patients were analyzed by age group (18-40, 41-60, and ≥61 years).

Results: Although disease severity/SCORAD scores were similar across AD age groups (mean, approximately 60 years; P = .873), dendritic cell infiltrates (CD1b and FcεRI, P < .05) decreased with age. T2 measures (IL5, IL13, CCL13, CCL18, and CCL26) significantly decreased with age in patients with AD, despite increasing with age in control subjects. Consistent with T2 axis decreases, serum IgE levels and eosinophil counts negatively correlated with age in patients with AD (r = -0.24 and r = -0.23, respectively; P < .05). T22-secreted IL22 expression levels also decreased with age uniquely in patients with AD (P < .05). Expression of T1-related (IFNG, IL12/23p40, STAT1, and CXCL9; P < .05 for CXCL9) and T17-related (IL17A and IL20; P < .05 for IL20) markers increased with age in both patients with AD and control subjects. Expression of terminal differentiation measures significantly increased in older patients with AD (loricrin [LOR] and filaggrin [FLG], P < .05), whereas expression of S100As (S100A8, P < .01) and hyperplasia markers (epidermal thickness, keratin 16, and Ki67; P < .05 for keratin 16) decreased. Serum trends in AD mimicked skin findings, with T2 downregulation (CCL26; r = -0.32, P < .1) and T1 upregulation (IFN-γ; r = 0.48, P < .01) with age.

Conclusion: The adult AD profile varies with age. Although T1/T17 skewing increases in both patients with AD and control subjects, patients with AD show unique decreases in T2/T22 polarization and normalization of epithelial abnormalities. Thus age-specific treatment approaches might be beneficial for AD.
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http://dx.doi.org/10.1016/j.jaci.2019.01.015DOI Listing
July 2019

A Phase 2 Randomized Trial of Apremilast in Patients with Atopic Dermatitis.

J Invest Dermatol 2019 05 5;139(5):1063-1072. Epub 2018 Dec 5.

Icahn School of Medicine at the Mount Sinai Medical Center, New York, New York, USA.

A phase 2, double-blind, placebo-controlled trial evaluated apremilast efficacy, safety, and pharmacodynamics in adults with moderate to severe atopic dermatitis. Patients were randomly assigned to receive placebo, apremilast 30 mg twice daily (APR30), or apremilast 40 mg twice daily (APR40) for 12 weeks. During weeks 12-24, all patients received APR30 or APR40. A biopsy substudy evaluated atopic dermatitis-related biomarkers. Among 185 randomly assigned intent-to-treat patients at week 12, a dose-response relationship was observed; APR40 (n = 63), but not APR30 (n = 58), led to statistically significant improvements (vs. placebo, n = 64) in Eczema Area and Severity Index (mean [standard deviation] percent change from baseline = -31.6% [44.6] vs. -11.0% [71.2], P < 0.04; primary endpoint). mRNA expression of T helper type 17/T helper type 22-related markers (IL-17A, IL-22, and S100A7/A8; P < 0.05) showed the highest reductions with APR40, with minimal changes in other immune axes. Safety with APR30 was largely consistent with apremilast's known profile (common adverse events: nausea, diarrhea, headache, and nasopharyngitis). With APR40, adverse events were more frequent, and cellulitis occurred (n = 6). An independent safety monitoring committee discontinued the APR40 dosage. APR40 showed modest efficacy and decreased atopic dermatitis-related biomarkers in moderate to severe atopic dermatitis patients. Adverse events, including cellulitis, were more frequent with APR40, which was discontinued during the trial. Clinical Trial Registration Number: NCT02087943 (clinicaltrials.gov).
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http://dx.doi.org/10.1016/j.jid.2018.10.043DOI Listing
May 2019

Philadelphia Telemedicine Glaucoma Detection and Follow-up Study: Ocular Findings at Two Health Centers.

J Health Care Poor Underserved 2018 ;29(4):1400-1415

Blindness from glaucoma can be prevented by early detection and treatment. Telemedicine improves access to treatment in high-risk populations that face barriers to receiving adequate ophthalmic care. We used a practice-based telemedicine screening model at two health centers. Telemedicine imaging of the fundus and optic nerve, followed by a complete eye exam at the same location for participants with abnormal findings, unreadable images, or ocular hypertension (OHTN), was performed. A total of 182 participants were screened, of whom 108 qualified for a complete eye exam. Of these, 62 (34.1%) had abnormal images, 12 (6.6%) had OHTN, and 34 (18.7%) had unreadable images. Eighty-nine of the 108 (82%) returned for the complete eye exam. Predominantly, participants were African American with glaucoma suspect and cataract. Screening location was an important factor for follow-up. Assessment of the fundus and optic disc using telemedicine resulted in early detection of glaucoma and other ocular pathology.
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http://dx.doi.org/10.1353/hpu.2018.0103DOI Listing
September 2019

Uveal Metastasis: Clinical Features and Survival Outcome of 2214 Tumors in 1111 Patients Based on Primary Tumor Origin.

Middle East Afr J Ophthalmol 2018 Apr-Jun;25(2):81-90

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: The purpose of this study is to evaluate patients with uveal metastasis based on primary tumor site.

Methods: Retrospective analysis from Wills Eye Hospital, Philadelphia, PA, USA, for uveal metastasis clinical features and outcomes based on the primary tumor site.

Results: There were 2214 uveal metastases diagnosed in 1111 consecutive patients. The demographics included mean age of 60 years (median 61 years), Caucasian race (88%), and female gender (64%). The tumor was unilateral (82%) and primary site was established before uveal metastasis (67%). The primary tumor originated in the breast (37%), lung (26%), kidney (4%), gastrointestinal (GI) tract (4%), cutaneous melanoma (2%), lung carcinoid (2%), prostate (2%), thyroid (1%), pancreas (1%), other sites (3%), and unknown (16%). Comparative analysis of the 5 most common primary sites (breast, lung, kidney, GI tract, and cutaneous melanoma), revealed metastasis at mean age (57, 62, 66, 61, 59 years), as unilateral tumor (74%, 86%, 85%, 93%, 85%), with mean number of metastasis/eye (1.9, 1.7, 1.0, 1.1, 2.0), and in females (99%, 46%, 26%, 25%, 30%). Choroidal metastases measured mean base (9.3, 10.2, 9.1, 11.0, 7.3 mm), mean thickness (2.4, 3.6, 4.4, 4.0, 2.9 mm), and demonstrated predominant color yellow (94%, 91%, 56%, 97%, 36%). Of the 769 patients with documented follow-up, mean patient survival was poor (22.2, 11.5, 8.6, 12.4, 11.4 months) and Kaplan-Meier analysis revealed 3-year survival (33%, 19%, 0%, 14%, 21%) and 5-year survival (24%, 13%, 0%, 14%, 21%). The worst survival was found in patients with pancreatic metastasis (mean 4.2 months) and best survival with lung carcinoid (92% at 5 years).

Conclusion: In a tertiary referral service, uveal metastasis originates from cancer in the breast, lung, kidney, GI tract, cutaneous melanoma, or others. Overall prognosis is poor with 5-year survival at 23% and worst survival with pancreatic metastasis whereas best survival with lung carcinoid metastasis.
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http://dx.doi.org/10.4103/meajo.MEAJO_6_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071342PMC
September 2018

Baseline IL-22 expression in patients with atopic dermatitis stratifies tissue responses to fezakinumab.

J Allergy Clin Immunol 2019 01 17;143(1):142-154. Epub 2018 Aug 17.

Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: IL-22 is potentially a pathogenic cytokine in patients with atopic dermatitis (AD), but the molecular effects of IL-22 antagonism have not been defined in human subjects.

Objective: We sought to evaluate the cellular and molecular effects of IL-22 blockade in tissues from patients with moderate-to-severe AD.

Methods: We assessed lesional and nonlesional skin from 59 patients with moderate-to-severe AD treated with anti-IL-22 (fezakinumab) versus placebo (2:1) using transcriptomic and immunohistochemistry analyses.

Results: Greater reversal of the AD genomic profile was seen with fezakinumab versus placebo, namely 25.3% versus 10.5% at 4 weeks (P = 1.7 × 10) and 65.5% versus 13.9% at 12 weeks (P = 9.5 × 10), respectively. Because IL-22 blockade showed clinical efficacy only in patients with severe AD, we used baseline median IL-22 mRNA expression to stratify for high (n = 30) and low (n = 29) IL-22 expression groups. Much stronger mean transcriptomic improvements were seen with fezakinumab in the IL-22-high drug-treated group (82.8% and 139.4% at 4 and 12 weeks, respectively) than in the respective IL-22-high placebo-treated group (39.6% and 56.3% at 4 and 12 weeks) or the IL-22-low groups. Significant downregulations of multiple immune pathways, including T1/CXCL9, T2/CCL18/CCL22, T17/CCL20/DEFB4A, and T22/IL22/S100A's, were restricted to the IL-22-high drug group (P < .05). Consistently, tissue predictors of clinical response were mostly genes involved in T-cell and dendritic cell activation and differentiation.

Conclusions: This is the first report showing a profound effect of IL-22 blockade on multiple inflammatory pathways in AD. These data, supported by robust effects in patients with high IL-22 baseline expression, suggest a central role for IL-22 in AD, indicating the need for a precision medicine approach for improving therapeutic outcomes in patients with AD.
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http://dx.doi.org/10.1016/j.jaci.2018.07.028DOI Listing
January 2019

INTRAVITREAL MELPHALAN FOR TREATMENT OF VITREOUS SEEDING FROM CHOROIDAL MELANOMA.

Retin Cases Brief Rep 2021 Mar;15(2):97-100

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: To report treatment of vitreous seeding of choroidal melanoma with monthly injections of intravitreal melphalan.

Methods: Case report.

Results: A 70-year-old white woman noted floaters in her left eye, and further examination revealed visual acuity of 20/30 in both eyes. Funduscopically, there was a mushroom-shaped choroidal melanoma in her left eye, measuring 9 mm in basal dimension and 4.8 mm in thickness. Notably, there was apical retinal invasion of melanoma with mild vitreous hemorrhage, without vitreous seeding. The tumor was treated with iodine-125 plaque radiotherapy using an apex dose of 70 Gy over 99 hours, designed to include the retinal invasion. The melanoma demonstrated complete regression into a nearly flat scar of 1 mm and remained stable over 4 years. Five years after radiotherapy, there were diffuse vitreous pigmented seeds of presumed melanoma origin, emanating from the site of retinal necrosis. This progressively worsened over the following 18 months, suspicious for viable melanoma cells, as visual acuity concurrently declined to 20/100. Treatment with intravitreal melphalan (10 μg/0.05 mL) was delivered on a monthly basis for 12 cycles, resulting in vitreous seeds regression, and preservation of the eye. Final visual acuity was 20/200. There were no treatment-related complications.

Conclusion: Intravitreal melphalan can be considered in cases of vitreous seeding from uveal melanoma.
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http://dx.doi.org/10.1097/ICB.0000000000000798DOI Listing
March 2021

An integrated model of alopecia areata biomarkers highlights both T1 and T2 upregulation.

J Allergy Clin Immunol 2018 11 5;142(5):1631-1634.e13. Epub 2018 Jul 5.

Department of Dermatology, Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2018.06.029DOI Listing
November 2018

Author Correction: The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins.

Sci Rep 2018 May 29;8(1):8439. Epub 2018 May 29.

The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-26378-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974294PMC
May 2018

Ichthyosis molecular fingerprinting shows profound T17 skewing and a unique barrier genomic signature.

J Allergy Clin Immunol 2019 02 24;143(2):604-618. Epub 2018 May 24.

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. Electronic address:

Background: Ichthyoses are a group of rare skin disorders lacking effective treatments. Although genetic mutations are progressively delineated, comprehensive molecular phenotyping of ichthyotic skin could suggest much-needed pathogenesis-based therapy.

Objective: We sought to profile the molecular fingerprint of the most common orphan ichthyoses.

Methods: Gene, protein, and serum studies were performed on skin and blood samples from 29 patients (congenital ichthyosiform erythroderma, n = 9; lamellar ichthyosis, n = 8; epidermolytic ichthyosis, n = 8; and Netherton syndrome, n = 4), as well as age-matched healthy control subjects (n = 14), patients with psoriasis (n = 30), and patients with atopic dermatitis (AD; n = 16).

Results: Using criteria of a fold change of greater than 2 and a false discovery rate of less than 0.05, 132 differentially expressed genes were shared commonly among all ichthyoses, including many IL-17 and TNF-α-coregulated genes, which are considered hallmarks of psoriasis (defensin beta 4A, kynureninase, and vanin 3). Although striking upregulation of TH17 pathway genes (IL17F and IL36B/G) resembling that seen in patients with psoriasis was common to all patients with ichthyoses in a severity-related manner, patients with Netherton syndrome showed the greatest T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with T1/IFN-γ, OASL, and T2/IL-4 receptor/IL-5 skewing, although less than seen in patients with AD (all P < .05). Ichthyoses lacked the epidermal differentiation and tight junction alterations of patients with AD (loricrin, filaggrin, and claudin 1) but showed characteristic alterations in lipid metabolism genes (ELOVL fatty acid elongase 3 and galanin), with parallel reductions in extracellular lipids and corneocyte compaction in all ichthyoses except epidermolytic ichthyosis, suggesting phenotypic variations. Transepidermal water loss, a functional barrier measure, significantly correlated with IL-17-regulated gene expression (IL17F and IL36A/IL36B/IL36G).

Conclusion: Similar to patients with AD and psoriasis, in whom cytokine dysregulation and barrier impairment orchestrate disease phenotypes, psoriasis-like immune dysregulation and lipid alterations characterize the ichthyoses. These data support the testing of IL-17/IL-36-targeted therapeutics for patients with ichthyosis similar to those used in patients with psoriasis.
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http://dx.doi.org/10.1016/j.jaci.2018.03.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195861PMC
February 2019

Spontaneous Hyphema in a Middle-aged Woman.

JAMA Ophthalmol 2018 07;136(7):829-830

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1001/jamaophthalmol.2017.6058DOI Listing
July 2018

The Major Orphan Forms of Ichthyosis Are Characterized by Systemic T-Cell Activation and Th-17/Tc-17/Th-22/Tc-22 Polarization in Blood.

J Invest Dermatol 2018 10 14;138(10):2157-2167. Epub 2018 Apr 14.

Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Illinois, USA. Electronic address:

The ichthyoses are rare skin disorders with immune and barrier aberrations. Identifying blood phenotypes may advance targeted therapeutics. We aimed to compare frequencies of skin homing/cutaneous lymphocyte antigen (+) versus systemic/cutaneous lymphocyte antigen (-) "polar" CD4/CD8 and activated T-cell subsets in ichthyosis versus atopic dermatitis, psoriasis, and control blood, with appropriate clinical correlations. Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4/CD8 T cells, with inducible co-stimulator molecule and HLA-DR defining mid- and long-term T-cell activation, respectively. We compared peripheral blood from 47 patients with ichthyosis (congenital ichthyosiform erythroderma, lamellar ichthyosis, epidermolytic ichthyosis, and Netherton syndrome) with 43 patients with atopic dermatitis and 24 patients with psoriasis and 59 age-matched controls. Clinical measures included the ichthyosis severity score, with subsets for erythema and scaling, transepidermal water loss, and pruritus. All ichthyoses had excessive inducible co-stimulator molecule activation (P < 0.001), particularly epidermolytic ichthyosis. Significantly elevated IL-17- (P < 0.05) and IL-22-producing (P < 0.01) T cells characterized ichthyoses, mainly Netherton syndrome and congenital ichthyosiform erythroderma (P < 0.05). Increased T helper 2/cytotoxic T cell 2/T helper 9 (P < 0.05) and similar IFN-γ frequencies (P > 0.1) versus controls were also noted. IL-17/IL-22-producing cells clustered with clinical measures, whereas IFN-γ clustered with age. Our data show peripheral blood IL-17/IL-22 activation across the ichthyoses, correlating with clinical measures. Targeted therapies should dissect the relative contribution of polar cytokines to disease pathogenesis.
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http://dx.doi.org/10.1016/j.jid.2018.03.1523DOI Listing
October 2018

Serum from Asian patients with atopic dermatitis is characterized by T2/T22 activation, which is highly correlated with nonlesional skin measures.

J Allergy Clin Immunol 2018 07 11;142(1):324-328.e11. Epub 2018 Apr 11.

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2018.02.047DOI Listing
July 2018

Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis: A randomized controlled trial.

Ann Allergy Asthma Immunol 2018 06 19;120(6):631-640.e11. Epub 2018 Mar 19.

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York. Electronic address:

Background: Liver X receptors (LXRs) are involved in maintaining epidermal barrier and suppressing inflammatory responses in model systems. The LXR agonist VTP-38543 showed promising results in improving barrier function and inflammatory responses in model systems.

Objective: To assess the safety, tolerability, cellular and molecular changes, and clinical efficacy of the topical VTP-38543 in adults with mild to moderate atopic dermatitis (AD).

Methods: A total of 104 ambulatory patients with mild to moderate AD were enrolled in this randomized, double-blind, vehicle-controlled trial between December 2015 and September 2016. VTP-38543 cream in 3 concentrations (0.05%, 0.15%, and 1.0%) or placebo was applied twice daily for 28 days. Pretreatment and posttreatment skin biopsy specimens were obtained from a subset of 33 patients. Changes in SCORing of Atopic Dermatitis, Eczema Area and Severity Index, Investigator's Global Assessment, and tissue biomarkers (by real-time polymerase chain reaction and immunostaining) were evaluated.

Results: Topical VTP-38543 was safe and well tolerated. VTP-38543 significantly increased messenger RNA (mRNA) expression of epidermal barrier differentiation (loricrin and filaggrin, P = .02) and lipid (adenosine triphosphate-binding cassette subfamily G member 1 and sterol regulatory element binding protein 1c, P < .01) measures and reduced epidermal hyperplasia markers (thickness, keratin 16 mRNA). VTP-38543 nonsignificantly suppressed cellular infiltrates and down-regulated mRNA expression of several T17/T22-related (phosphatidylinositol 3, S100 calcium-binding protein A12) and innate immunity (interleukin 6) markers.

Conclusion: Topical VTP-38543 is safe and well tolerated. Its application led to improvement in barrier differentiation and lipids. Longer-term studies are needed to clarify whether a barrier-based approach can induce meaningful suppression of immune abnormalities.

Trial Registration: clinicaltrials.gov Identifier: NCT02655679.
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http://dx.doi.org/10.1016/j.anai.2018.03.013DOI Listing
June 2018

Lynch Syndrome and Muir-Torre Syndrome: An update and review on the genetics, epidemiology, and management of two related disorders.

Dermatol Online J 2017 Nov 15;23(11). Epub 2017 Nov 15.

Albert Einstein College of Medicine, Bronx, New York.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, is an autosomal dominant, tumor predisposing disorder usuallycaused by germline mutations in mismatch repair (MMR) genes. A subset of HNPCC, Muir-Torre Syndrome (MTS) also involves MMR gene defects and is generally accepted as a variant of HNPCC. MTS is typicallycharacterized by at least one visceral malignancy and one cutaneous neoplasm of sebaceous differentiation, with or without keratoacanthomas. In either version of the disorder, nonfunctional MMR systems lead tothe loss of genomic integrity, marked commonly by mismatches in repetitive DNA sequences, resulting in microsatellite instabilities. Deleterious nucleotide alterations ultimately drive the process of tumorigenesis in both HNPCC and MTS. The following article reviews the epidemiology, genetics, clinical presentation, and management of HNPCC and its MTS variant.
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November 2017

HAND-HELD OPTICAL COHERENCE TOMOGRAPHY MONITORING OF CHEMORESISTANT RETINOBLASTOMA.

Retin Cases Brief Rep 2020 ;14(4):368-371

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: Retinoblastoma (Rb) is a potentially fatal intraocular malignancy in children, and hand-held optical coherence tomography (HH-OCT) can assist in submillimeter detection and monitoring after treatment of Rb. Retinoblastoma located in the macula, or those with chemoresistance, can be among the most difficult to manage. We describe HH-OCT features in a case of chemoresistant macular Rb that eventually responded to plaque radiotherapy after failing intravenous chemotherapy and intraarterial chemotherapy.

Methods: Observational case report.

Results: A 15-month-old girl with leukocoria was found to have Group D Rb in the right eye of 6-mm thickness and macular Group B Rb in the left eye of 4-mm thickness. She was treated with 6-monthly cycles of systemic intravenous chemotherapy and focal consolidation therapies to both eyes, with tumor regression in both eyes. However, macular tumor in the left eye demonstrated subsequent recurrence, from regressed thickness of 792 μm on HH-OCT to a dome-shaped hyperreflective retinal mass of >2000 μm thickness. Three cycles of intraarterial chemotherapy were sufficient for tumor regression down to 977 μm thickness on HH-OCT. Six months later, macular tumor in the left eye recurred again to >2000 μm thickness and necessitated plaque radiotherapy using apex dose of 35 Gy over 95.25 hours. Hand-held OCT confirmed rapid tumor regression to 722 μm after plaque treatment and regression remained stable at 6-month follow-up.

Conclusion: Hand-held OCT was critical in assessment of Rb after failed intravenous chemotherapy and intraarterial chemotherapy and later documenting regression after plaque radiotherapy. Hand-held OCT is vital in providing cross-sectional imaging and measurements of small macular and paramacular Rbs.
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http://dx.doi.org/10.1097/ICB.0000000000000714DOI Listing
July 2021

Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial.

J Am Acad Dermatol 2018 05 17;78(5):872-881.e6. Epub 2018 Jan 17.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.

Background: Interleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function.

Objective: Evaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD).

Methods: We performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point.

Results: At 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 ± 2.7 in the fezakinumab arm and 8.0 ± 3.1 in the placebo arm (P = .134). In the severe AD patient subset (with a baseline SCORAD of ≥50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 ± 3.8 vs 9.6 ± 4.2, P = .029) and 20 weeks (27.4 ± 3.9 vs 11.5 ± 5.1, P = .010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% ± 2.4 vs 6.2% ± 2.7; P = .009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 ± 0.2 vs 0.3 ± 0.1; P = .034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections.

Limitations: The limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD.

Conclusion: Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.
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http://dx.doi.org/10.1016/j.jaad.2018.01.016DOI Listing
May 2018
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