Hajirah N. Saeed

SJS/TEN 2017: Building Multidisciplinary Networks to Drive Science and Translation

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening, immunologically mediated, and usually drug-induced disease with a high burden to individuals, their families, and society with an annual incidence of 1 to 5 per 1,000,000. To effect significant reduction in short- and long-term morbidity and mortality, and advance clinical care and research, coordination of multiple medical, surgical, behavioral, and basic scientific disciplines is required. On March 2, 2017, an investigator-driven meeting was held immediately before the American Academy of Dermatology Annual meeting for the central purpose of assembling, for the first time in the United States, clinicians and scientists from multiple disciplines involved in SJS/TEN clinical care and basic science research. As a product of this meeting, this article summarizes the current state of knowledge and expert opinion related to SJS/TEN covering a broad spectrum of topics including epidemiology and pharmacogenomic networks; clinical management and complications; special populations such as pediatrics, the elderly, and pregnant women; regulatory issues and the electronic health record; new agents that cause SJS/TEN; pharmacogenomics and immunopathogenesis; and the patient perspective. Goals include the maintenance of a durable and productive multidisciplinary network that will significantly further scientific progress and translation into prevention, early diagnosis, and management of SJS/TEN.

Ocular manifestations of Stevens-Johnson syndrome and their management.

Purpose of review Recent advances and outcomes data in the management of Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) demonstrate the need for a universal standard of care for patients admitted with the disease. Recent findings Amniotic membrane transplantation, aggressive topical corticosteroids, and lubrication in the acute stage are necessary to prevent or mitigate long-term ocular sequelae. If chronic ocular disease does occur, several interventions can be employed to prevent progressive vision loss and discomfort. The earliest interventions are the ones most likely to prevent chronic complications. Summary The literature overwhelmingly describes acute intervention for ocular involvement in SJS/TEN as improving long-term outcomes. All patients admitted for SJS/TEN or suspicion of SJS/TEN should be evaluated and then closely followed by ophthalmologists. As the disease progresses, the interventions needed for visual rehabilitation become more invasive and higher risk.

Burn unit care of Stevens Johnson syndrome/toxic epidermal necrolysis: A survey

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a systemic disease that can be associated with debilitating acute and chronic complications across multiple organ systems. As patients with acute SJS/TEN are often treated in a burn intensive care unit (BICU), we surveyed burn centers across the United States to determine their approach to the care of these patients. The goal of our study was to identify best practices and possible variations in the care of patients with acute SJS/TEN. We demonstrate that the method of diagnosis, use of systemic therapies, and involvement of subspecialists varied significantly between burn centers. Beyond supportive care provided to every patient, our data highlights a lack of standardization in the acute care of patients with SJS/TEN. A comprehensive guideline for the care of patients with acute SJS/TEN is indicated.

The Boston keratoprosthesis

Purpose of review The Boston keratoprosthesis (BKPro) is often the only hope for visual rehabilitation in severe corneal disease. Since Food and Drug Administration approval of the device in 1992, there have been a series of advances in its design, surgical techniques, and postoperative care, which have widened its applicability and decreased associated complications. The purpose of this review is to highlight the indications, management, outcomes, and advances in the BKPro literature. Recent findings With more surgeons reporting long-term data, it is evident that modifications to the device and perioperative care have led to higher rates of device retention and improved visual outcomes. Recent data also suggest that BKPro may be superior to traditional corneal transplant in the setting of a previously failed graft. There may be advantages to implantation of the device earlier in the course of some diseases without an increased risk of postoperative complications. Devices to reliably measure intraocular pressure and imaging modalities to provide improved visualization of intraocular structures have the potential to further improve outcomes. Summary The current indications for implantation of the BKPro have broadened. Initially considered a surgery of last resort, the clinical indications for use of the BKPro continue to grow. Early detection and management of postoperative complications can mitigate vision loss and improve outcomes.

Stevens-Johnson Syndrome and Corneal Ectasia: Management and a Case for Association

PURPOSE To report the occurrence of corneal ectasia (ECT) in patients with history of Stevens-Johnson syndrome (SJS), and to make the case for an association between these 2 diagnoses. We also report the impact of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment on visual acuity (VA) in these patients. DESIGN Retrospective cohort study. METHODS A manufacturing database of PROSE patients from 2002 to 2014 at Boston Foundation for Sight (BFS), a single-center clinical practice, was reviewed to identify patients with diagnoses of both SJS and ECT. RESULTS Nine patients were identified with diagnoses of both SJS and ECT. In each case, review of the medical record revealed that diagnosis of SJS preceded that of ECT. The prevalence of ECT in this population exceeded that in the general population (P < .0001). Videokeratography was available for 13 eyes in 7 patients; using Krumeichs classification of keratoconus, 3 eyes were found to be at stage 1, 3 at stage 2, 1 at stage 3, and 6 at stage 4. Sixteen of 18 eyes underwent PROSE treatment. Of these 16 eyes, initial median VA was 20/200 (range, count fingers to 20/20; logMAR 1.0). Median VA after PROSE customization was 20/30 (range, 20/60-20/15; logMAR 0.1761, P < .0025). CONCLUSIONS ECT occurs at a higher-than-expected rate in patients with a history of SJS. PROSE treatment improves VA in these patients. The basis of the association between SJS and ECT is considered, as well as the role of plausible contributory factors such as corneal microtrauma and matrix metalloproteinases.

Keratolimbal allograft for limbal stem cell deficiency after severe corneal chemical injury: a systematic review

Purpose To review the published literature on outcomes of keratolimbal allograft (KLAL) for the surgical treatment of limbal stem cell deficiency (LSCD) and corneal blindness after severe corneal chemical injury. Methods Literature searches were conducted in the following electronic databases: MEDLINE, EMBASE, Science Citation Index, CINAHL, LILACS and the Cochrane Library. Standard systematic review methodology was applied. The main outcome measure was the proportion of eyes with best-corrected visual acuity (BCVA) ≥20/200 at last follow-up. Other measures of allograft success were also collected. Results We identified six reports in which KLAL outcomes in the eyes after chemical injury could be distinguished. There were no randomised controlled studies. The outcomes of KLAL in 36 eyes of 33 patients were analysed. One study with seven eyes did not specify KLAL follow-up specific to chemical injury. Median postoperative follow-up for the other 29 eyes in 26 patients was 42 months (range 6.2–114 months). In the same 29 eyes, 69% (20/29) had BCVA ≥20/200 at the last follow-up examination. Eighty-nine per cent of all eyes (32/36) underwent penetrating keratoplasty simultaneous or subsequent to KLAL. Conclusions The number of studies where outcomes of KLAL in eyes with severe corneal chemical injury could be discerned was limited, and variability was observed in outcome reporting. The quality of evidence to support the use of KLAL in LSCD in severe chemical corneal burns was low. Standardisation and longer follow-up are needed to better define evidence-based best practice when contemplating surgical intervention for blindness after corneal chemical injury. PROSPERO registration number CRD42017054733.

Immunologic Mediators in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

ABSTRACT Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are a spectrum of T-cell mediated immune disorders. While the contributory mechanisms leading to the apoptosis of epidermal cells in SJS/TEN remain unproven, the keratinocyte apoptosis seen in SJS/TEN is thought to occur through the T-cell mediated Fas-Fas ligand (FasL), perforin/granzyme B, and other immune mediators. Most recently, emphasis has been placed on the granulysin pathway as being the primary mediator of apoptosis and widespread epidermal necrosis in SJS/TEN. This article aims to review the proposed mechanisms by which these pathways work and the immunomodulatory therapies that have been developed in an attempt to target them.

Boston keratoprosthesis type 1 for limbal stem cell deficiency after severe chemical corneal injury: A systematic review

PURPOSE To systematically review the published literature on outcomes of Boston keratoprosthesis type 1 for the treatment of limbal stem cell deficiency secondary to severe chemical corneal injury. METHODS Literature searches were conducted in MEDLINE (Ovid), Embase, Web of Science, and the Cochrane Central Register. The main outcome measures assessed were the proportion of eyes with best-corrected visual acuity (BCVA) ≥ 20/200 and the proportion retaining their original keratoprosthesis, both at the last recorded visit. RESULTS We identified 9 reports in which outcomes of Boston keratoprosthesis type I implantation after severe chemical injury could be determined, encompassing a total of 106 eyes of 100 patients. There were no randomized controlled studies. The median pre-operative BCVA was hand motion. Vision improved to ≥20/200 in 99/106 (93.4%) eyes after implantation. With a mean follow-up of 24.99 ± 14 months, 68/106 (64.1%) eyes retained BCVA ≥ 20/200 at the last examination. Therefore, 68/99 (68.7%) of those who improved to > 20/200 maintained at least this acuity. The originally implanted device was retained in 88/99 (88.9%) recipients for whom retention was reported. The mean time to failure was 22.36 ± 17.2 months. Glaucomatous optic neuropathy was the most common cause for BCVA <20/200 in eyes that retained the keratoprosthesis (18/27, 66.7%).. CONCLUSIONS Implantation of a Boston keratoprosthesis type I in eyes with corneal blindness after severe chemical ocular injury leads to functional vision in the majority of recipients. Evidence was limited by variability in outcome reporting and an absence of controlled studies..

Advances in Imaging of Ocular Surface Tumors

Diagnosis in ophthalmology relies on proper visualization by the provider, whether it be a corneal ulcer or age-related macular degeneration. Technological developments have dramatically altered how we approach and manage such disease processes. For example, we can use optical coherence tomography (OCT) of the macula to evaluate for subretinal fluid, anterior segment ultrasound biomicroscopy (UBM) to evaluate a plateau iris configuration, and confocal microscopy to evaluate fungal corneal ulcers. Although the use of imaging modalities has become routine in ophthalmology, imaging of ocular surface tumors represents a relatively new advancement. Ophthalmologists encounter a variety of ocular surface lesions, from pterygia and pingueculae to conjunctival nevi and melanomas. There is often overlap of clinical appearances between benign and malignant lesions, and sometimes arriving at the correct diagnosis can be challenging. Clinical history can help direct evaluation and subsequent treatment, but many times, the diagnosis remains elusive. Recent advances in imaging have allowed for a greater understanding of a wide-range of ocular surface tumors and have helped guide the approach to and management of these lesions. The goal of this review is to unveil the depth and breadth of the imaging armamentarium available when encountering ocular surface tumors.