Akbar Shakoor

Recurrence of Uveitis after Discontinuation of Infliximab

Abstract Purpose: To evaluate the recurrence of uveitis after discontinuation of infliximab once control of inflammation is achieved. Methods: A retrospective cohort study was conducted of patients seen at the Proctor Foundation between 1998 and 2010 who discontinued infliximab after achieving corticosteroid-sparing control by Standardization of Uveitis Nomenclature criteria. The main outcome was the proportion of patients who had a relapse of uveitis. Results: Eighteen patients attempted to discontinue infliximab after achieving control of inflammation, and 11 patients had a relapse. Median time to relapse was 603 days (95% CI: 85–1461 days). Patients with juvenile idiopathic arthritis (JIA)-associated uveitis (nu2009=u20094) relapsed faster (median time to relapse: 76 days, pu2009=u20090.002) compared with patients who did not have JIA-associated uveitis (medianu2009=u20091169 days). Conclusions: The majority of patients who achieved control of inflammation on infliximab had a recurrence after discontinuing therapy. Patients with JIA experienced recurrence faster compared to other patients.

Uveitis in human immunodeficiency virus-infected persons with CD4+ T-lymphocyte count over 200 cells/mL

Introduction of highly active antiretroviral therapy has altered the course of disease for persons infected with human immunodeficiency virus by elevating CD4+ T‐lymphocyte levels. Changes in the spectrum of systemic diseases encountered in human immunodeficiency virus‐positive individuals are reported in the general medical literature.

Genetics of age-related macular degeneration (AMD)

Age-related macular degeneration (AMD) is a progressive blinding disease and represents the leading cause of visual impairment in the aging population. AMD affects central vision which impairs ones ability to drive, read and recognize faces. There is no cure for this disease and current treatment modalities for the exudative form of the disease require repeated intravitreal injections which may be painful, are incompletely efficacious, and represent a significant treatment burden for both the patient and physician. As such, AMD represents a significant and important clinical problem.It is anticipated that in three years time, 196 million individuals will be affected with AMD. Over 250 billion dollars per year are spent on care for AMD patients in the US. Over half of the heritability is explained by two major loci, thus AMD is considered the most well genetically defined of the complex disorders. A recent GWAS on 43,566 subjects identified novel loci and pathways associated with AMD risk, which has provided an excellent platform for additional functional studies. Genetic variants have been investigated, particularly with respect to anti-VEGF treatment, however to date, no pharmacogenomic associations have been consistently identified across these studies. It may be that if the goal of personalized medicine is to be realized and biomarkers are to have predictive value for determining the magnitude of risk for AMD at the genetic level, one will need to examine the relationships between these pathways across disease state and relative to modifiable risk factors such as hypertension, smoking, body mass index, and hypercholesterolemia. Further studies investigating protective alleles in populations with low AMD prevalence may lead to this goal.

Use of Immunosuppressive Medications for Treatment of Pediatric Intermediate Uveitis

ABSTRACT Purpose: To describe the treatment and outcomes of a cohort of pediatric intermediate uveitis (IU) patients, with a particular focus on the use of immunomodulatory therapy (IMT). Methods: The disease course, treatment, and outcomes of 39 pediatric IU patients treated in the Uveitis Clinic at the University of Utah from 1999 to 2012 were reviewed, retrospectively. Results: Mean age at presentation was 7.7 years (SD 3.1). In total, 95% had bilateral involvement. Out of 77 total eyes involved, the most frequent disease complications were ocular hypertension (0.71 events per person year, PPY), cataracts (events PPY = 0.39), and cystoid macular edema (events PPY = 0.33). A total of 20 patients received IMT; 19/20 were tapered off systemic corticosteroids without a uveitis recurrence; 75% of eyes had inactive disease at final follow-up (mean 37 months). Conclusions: The use of IMT, including biologic therapies, may effectively manage disease inflammation and reduce steroid dosages in pediatric IU patients.

The First Case of Trypanosoma cruzi–Associated Retinitis in an Immunocompromised Host Diagnosed With Pan-Organism Polymerase Chain Reaction

We report the first case of Trypanosoma cruzi-associated retinitis diagnosed using 28s ribosomal DNA sequencing. The case highlights the utility of broad-range molecular diagnostics for detecting rare and unsuspected ocular pathogens. Ocular involvement in Chagas disease is also discussed.

Stroke Due to Cerebral Vasculitis in a Patient with Relentless Placoid Chorioretinitis

ABSTRACT Purpose: To report the first case of stroke in a patient with relentless placoid chorioretinitis. Methods: Observational case report. Results: A 20-year-old female with newly diagnosed relentless placoid chorioretinitis was urgently evaluated for unilateral paresthesias. She was found to have acute bilateral pontine strokes and cerebral vasculitis on magnetic resonance imaging of the brain and cerebral angiography. Conclusions: We report the first case of stroke due to cerebral vasculitis in a patient with relentless placoid chorioretinitis. This case emphasizes the need for timely evaluation of neurological symptoms in patients with this ocular diagnosis.

Relapse of Juvenile Idiopathic Arthritis-Associated Uveitis after Discontinuation of Immunomodulatory Therapy

ABSTRACT Purpose: To assess treatment outcomes in juvenile idiopathic arthritis (JIA)-associated uveitis and relapse rates upon discontinuation of immunomodulatory therapy (IMT). Methods: Medical records of patients with JIA-associated uveitis seen at the University of Illinois at Chicago and the F.I. Proctor Foundation uveitis clinics from September 14, 1988 to January 5, 2011 were reviewed. The main outcome was time to relapse after attempting to discontinue IMT.Results: Of 66 patients with JIA-associated uveitis, 51 (77%) received IMT as either sole or combination therapy. Of a total of 51, 41 (80%) patients achieved corticosteroid-sparing control. Attempts were made to discontinue treatment in 19/51 (37%) patients. Of a total of 19 patients, 13 (68%) attempting to discontinue IMT relapsed, with a median time to relapse of 288 days from the time of attempted taper/discontinuation (IQR: 108–338).Conclusions: Corticosteroid-sparing control of inflammation was achieved in the majority of patients; however, attempts to stop IMT were often unsuccessful. Close follow-up of patients after discontinuation of therapy is warranted.

Checkpoint inhibitor-induced uveitis: a case series

PurposeCheckpoint inhibitors are now a common treatment modality for metastatic cancer. In this manuscript, we describe the clinical features and management of autoimmune non-infectious uveitis induced by this class of drugs.MethodsSeven patients undergoing checkpoint inhibitor treatment for metastatic cancer from uveitis practices at three tertiary referral centers.ResultsAll seven patients developed various severities of ocular inflammatory disease while taking checkpoint inhibitors for metastatic disease.ConclusionsCheckpoint inhibitors may induce autoimmune uveitis. Ocular complaints should prompt an early evaluation by an ophthalmologist.

Current Strategies for Prevention and Treatment of Postoperative Endophthalmitis

Purpose of reviewWe review the prevention and treatment of postoperative endophthalmitis.Recent findingsPostoperative endophthalmitis is rare but has potentially blinding consequences. There is no consensus on prevention, but there are a few controlled studies with methods of decreasing the infection rate, such as use of povidone iodine and intracameral antibiotics. There remains only one randomized controlled study (Endophthalmitis Vitrectomy Study or EVS) on the treatment of postoperative endophthalmitis, but there are retrospective studies which examine the timing and various methods of vitrectomy and intravitreal antibiotics.SummaryThe application of povidone iodine remains a proven method of preventing endophthalmitis, but evidence suggests that intracameral antibiotics further minimize this risk. Further research is needed to define the efficacy of intravitreal antibiotics at the time of cataract surgery. There are many questions regarding treatment, including performance of vitrectomy for eyes with visual acuities better than light perception, smaller vitrectomy port sizes, and intravitreal antibiotics and/or oral steroids.

Corrigendum: Genetics of age-related macular degeneration (AMD) [Human Molecular Genetics, 26, R1, (2017) (R45-R50)] doi: 10.1093/hmg/ddx228

Genetics of age-related macular degeneration (AMD) Margaret M. DeAngelis*, Leah A. Owen, Margaux A. Morrison, Denise J. Morgan, Mingyao Li, Akbar Shakoor, Albert Vitale, Sudha Iyengar, Dwight Stambolian, Ivana K. Kim and Lindsay A. Farrer Department of Ophthalmology and Visual Sciences, John Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT 84132, USA, Department of Pharmacotherapy, L.S. Skaggs School of Pharmacy, University of Utah, Salt Lake City, UT 84132, USA, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH 44106, USA, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA, Department of Medicine (Biomedical Genetics), Department of Neurology, Department of Ophthalmology, Boston University Schools of Medicine, Boston, MA 02118, USA, Department of Biostatistics, and Department of Epidemiology, Boston University Schools of Public Health, Boston, MA 02118, USA