Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.

Epibulbar Mass With Upper Eyelid Cleft and Focal Scalp Alopecia in a Neonate: A New Case of Oculoectodermal Syndrome.

A female neonate presented with a pedunculated left lateral epibulbar mass protruding through the eyelids that originated from the temporal cornea and superolateral bulbar and palpebral conjunctiva. She had a cleft in the ipsilateral central upper eyelid with horizontal kink of the tarsus lateral to the cleft and focal patches of alopecia on the scalp. Histopathology of the epibulbar mass revealed conjunctival epithelium with underlying connective tissue, cartilage, bone, adipose, and lacrimal gland consistent with epibulbar dermoid. Genetic testing of the surgical specimen was positive for a KRAS mutation at position 146. MRI showed subarachnoid asymmetry around the left temporal lobe and a C1-C2 enhancing lesion. These clinical and molecular findings suggest that this patient has a new clinical variant of oculoectodermal syndrome, a rare disorder associated with somatic KRAS gene mutations and characterized clinically by epibulbar dermoids, alopecia, aplasia cutis, brain anomalies, umbilical hernias, and congenital heart defects.

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.

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.

Global Disparities in Access to Vaccine Clinical Trials: A Review of the Literature.

Vaccines are an effective tool to reduce the disease burden from infectious diseases on a population, infrastructural, and individual level. Before vaccines can be administered to populations at large, they must go through rigorous testing in the form of clinical trials. While vaccine trials can be used to assess the efficacy of interventions on a local populace as well as target local endemic diseases, most clinical trials are sponsored and conducted by companies in high-income countries (HICs). This can lead to vaccines that are not optimized for low- and middle-income countries (LMICs) and that often neglect to address diseases specific to the local population. This narrative review aims to explore the factors leading to discrepancies in the execution of and access to vaccine trials between HICs and LMICs, thus guiding future efforts in confronting them. This review was written using the literature sourced from the PubMed database and supplemented with articles from Google Scholar along with grey literature. Several themes are highlighted including poorly defined regulatory and ethical guidelines, staff shortages, lack of research infrastructure, and logistical barriers. We discuss how these challenges have affected vaccine development in various capacities through case examples of SARS-CoV-2, poliovirus, and malaria. Many challenges remain in equitable vaccine clinical trial development and implementation. Facilitating the implementation of locally sponsored vaccine clinical trials in LMICs may be one avenue to address these challenges. In doing so, LMICs can become active stakeholders in the health of their citizens by addressing endemic diseases, tailoring vaccine specifications based on local needs, and implementing wide-scale vaccine access and delivery.

Ocular lichen planus as a cause of recurrent restrictive strabismus.

We report the case of an 80-year-old man with restrictive strabismus in lateral gaze following multiple oculoplastic procedures for idiopathic epiphora. Despite excellent initial response to nasal conjunctival recession with lysis of adhesions and a miminal recession of the medial rectus muscle, the patient suffered recurrence of diplopia associated with limitation of abduction due to aggressive, deep, subconjunctival scarring. Given the history of oral lichen planus (LP), the patient was diagnosed with ocular involvement of LP. He underwent a second conjunctival recession, this time accompanied by an intensive LP treatment regimen. Nine months after surgery, he remained diplopia free and orthophoric in primary gaze. Surgeons treating restrictive strabismus in patients with LP should consider implementing systemic and topical immunosuppressive treatment simultaneously with surgical management.

Long-term outcomes of glued (sutureless) amniotic membrane transplantation in acute Stevens-Johnson syndrome/toxic epidermal necrolysis: a comparative study.

PURPOSE: To compare the effectiveness and efficiency of a glued (sutureless) technique for amniotic membrane transplantation (AMT) with a traditional sutured one in the setting of acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: This retrospective cohort study evaluated all patients diagnosed with SJS/TEN between 2008 and 2020 within our hospital network who received AMT in the acute phase according to our protocol and had at least one ophthalmic follow-up in the chronic phase. Primary outcomes included best-corrected visual acuity (BCVA) at the most recent visit, presence of a severe ocular complication (SOC) via predefined criteria, time to procedure and duration of procedure. Random effects model analysis was used to evaluate the impact of potential covariates on outcome measures. RESULTS: A total of 23 patients (45 eyes) were included: 14 patients (27 eyes) in the AMT suture group and 9 patients (18 eyes) in the AMT glue group. There was no difference between the two groups in BCVA at the most recent visit (p=0.5112) or development of a SOC (p=1.000). The glue method was shorter in duration than the suture method (p<0.001). Random effects model additionally indicated that there was no difference in BCVA at most recent follow-up between patients who had received glued versus sutured AMT (p=0.1460). CONCLUSIONS: Our glued technique for AMT is as effective as our sutured technique in stabilising the ocular surface and mitigating chronic ocular complications in SJS/TEN. The glued technique is also shorter in duration and performed more expediently than the sutured technique.

Disparities in Access to Corneal Tissue in the Developing World.

Corneal disease is a leading cause of blindness worldwide. For most blinding corneal conditions, keratoplasty is the only way of restoring sight. Unfortunately, access to corneal transplantation is widely variable, most notably due to the lack of suitable donor material. There exists significant disparity between the developed and developing world when it comes to access to cornea tissue, with supply often inversely proportional to burden of disease. The purpose of this review is to identify the current disparities in supply and demand of corneal donor tissue, understand how to access corneal tissue, and propose solutions that promote equitable care for patients with severe corneal disease.

Ocular involvement in allergic drug reactions.

PURPOSE OF REVIEW: Many systemic medications have been observed to cause ocular toxicity. A subset of these reactions is thought to involve immunomodulation or a hypersensitivity reaction. As new medications are developed, ocular adverse effects are becoming increasingly prevalent. Herein we review immune-mediated drug reactions affecting they eye with special attention to the hypersensitivity mechanisms leading to ocular toxicity. RECENT FINDINGS: Recent work has focused on mechanisms and risk of immune-mediated ocular adverse drug reactions including genetic susceptibility and loss of ocular immune privilege. SUMMARY: Given the consequences of immune-mediated ocular adverse drug reactions, clinicians must be aware of these to facilitate early recognition and management. The prompt involvement of an ophthalmologist for diagnosis and management is often essential to preserve vision and avoid long-term morbidity.

New Frontiers in Acanthamoeba Keratitis Diagnosis and Management.

Acanthamoeba Keratitis (AK) is a severe corneal infection caused by the Acanthamoeba species of protozoa, potentially leading to permanent vision loss. AK requires prompt diagnosis and treatment to mitigate vision impairment. Diagnosing AK is challenging due to overlapping symptoms with other corneal infections, and treatment is made complicated by the organism's dual forms and increasing virulence, and delayed diagnosis. In this review, new approaches in AK diagnostics and treatment within the last 5 years are discussed. The English-language literature on PubMed was reviewed using the search terms "Acanthamoeba keratitis" and "diagnosis" or "treatment" and focused on studies published between 2018 and 2023. Two hundred sixty-five publications were initially identified, of which eighty-seven met inclusion and exclusion criteria. This review highlights the findings of these studies. Notably, advances in PCR-based diagnostics may be clinically implemented in the near future, while antibody-based and machine-learning approaches hold promise for the future. Single-drug topical therapy (0.08% PHMB) may improve drug access and efficacy, while oral medication (i.e., miltefosine) may offer a treatment option for patients with recalcitrant disease.

Relationship between Atopic Disease and Acute Ocular and Systemic Outcomes in Patients with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

OBJECTIVE: To describe the relationship between history of atopic disease on systemic and ocular manifestations of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). METHODS: Retrospective chart review of patients with SJS/TEN patients. Those with and without prior atopic diagnosis were compared. RESULTS: In total, 200 patients with SJS/TEN were identified. A total of 23 patients also had an atopic diagnosis. Four, 10, and 18 had atopic dermatitis, allergic rhinitis, and asthma respectively. Acute ocular severity was significantly worse in the atopic cohort. No significant differences in overall systemic severity of SJS or mortality were found between the atopic and non-atopic cohorts. Compared to our hospital system's general population, prevalence of an atopic diagnosis was significantly higher in those with SJS/TEN. CONCLUSION: Patients with a history of an atopic diagnosis appear to have more significant acute ocular involvement during their SJS/TEN hospitalization. Atopic conditions appear to occur more frequently in the SJS/TEN population compared to the general population.

Corneal Adverse Events Associated with SARS-CoV-2/COVID-19 Vaccination: A Systematic Review.

Vaccines against coronavirus disease 2019 (COVID-19) have played an important global role in reducing morbidity and mortality from COVID-19 infection. While the benefits of vaccination greatly outweigh the risks, adverse events do occur. Non-ocular adverse effects of the vaccines have been well-documented, but descriptions of ophthalmic effects remain limited. This systematic review aims to provide an overview of reported cases of corneal adverse events after receiving vaccination against COVID-19 and to compile existing clinical data to bring attention to these phenomena. Our review discusses corneal graft rejection, including proposed mechanisms, herpetic keratitis, and other reported corneal complications. Ophthalmologists and primary care physicians should be aware of such possible associations.

Ocular involvement in Mycoplasma induced rash and mucositis: A systematic review of the literature.

Mycoplasma pneumoniae induced rash and mucositis (MIRM) is a relatively newly identified clinical entity which is characterized by mucocutaneous manifestations in the setting of Mycoplasma infection. Though a clinically distinct disease, MIRM exists on a diagnostic continuum with entities including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and the recently described reactive infectious mucocutaneous eruption (RIME). In this systematic review, we discuss published findings on the epidemiology, clinical manifestations, diagnosis, and management of MIRM, with an emphasis on ocular disease. Lastly, we discuss some of the most recent developments and challenges in characterizing MIRM with respect to the related diagnosis of RIME.

Sulfated motifs in heparan sulfate inhibit Streptococcus pneumoniae adhesion onto fibronectin and attenuate corneal infection.

A large number of bacterial pathogens bind to host extracellular matrix (ECM) components. For example, many Gram-negative and Gram-positive pathogens express binding proteins for fibronectin (FN) on their cell surface. Mutagenesis studies of bacterial FN-binding proteins have demonstrated their importance in pathogenesis in preclinical animal models. However, means to draw on these findings to design therapeutic approaches that specifically target FN-bacteria interactions have not been successful because bacterial pathogens can elaborate several FN-binding proteins and also because FN is an essential protein and likely a nondruggable target. Here we report that select heparan compounds potently inhibit Streptococcus pneumoniae infection of injured corneas in mice. Using intact heparan sulfate (HS) and heparin (HP), heparinase-digested fragments of HS, HP oligosaccharides, and chemically or chemoenzymatically modified heparan compounds, we found that inhibition of S. pneumoniae corneal infection by heparan compounds is not mediated by simple charge effects but by a selective sulfate group. Removal of 2-O-sulfates significantly inhibited the ability of HP to inhibit S. pneumoniae corneal infection, whereas the addition of 2-O-sulfates to heparosan (H) significantly increased H's ability to inhibit bacterial corneal infection. Proximity ligation assays indicated that S. pneumoniae attaches directly to FN fibrils in the corneal epithelial ECM and that HS and HP specifically inhibit this binding interaction in a 2-O-sulfate-dependent manner. These data suggest that heparan compounds containing 2-O-sulfate groups protect against S. pneumoniae corneal infection by inhibiting bacterial attachment to FN fibrils in the subepithelial ECM of injured corneas. Moreover, 2-O-sulfated heparan compounds significantly inhibited corneal infection in immunocompromised hosts, by a clinical keratitis isolate of S. pneumoniae, and also when topically administered in a therapeutic manner. These findings suggest that the administration of nonanticoagulant 2-O-sulfated heparan compounds may represent a plausible approach to the treatment of S. pneumoniae keratitis.

Incidence and risk factors for glaucoma development and progression after corneal transplantation.

OBJECTIVE: To assess the cumulative incidence and risk factors for glaucoma development and progression within 1-2 years following corneal transplant surgery. DESIGN: Retrospective cohort study. METHODS: Patients undergoing penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), Descemet stripping endothelial keratoplasty (DSEK), Descemet membrane endothelial keratoplasty (DMEK), Boston keratoprosthesis type I (KPro) implantation, or endothelial keratoplasty (DSEK or DMEK) under previous PK (EK under previous PK) at one academic institution with at least 1 year of follow-up were included. Primary outcome measures were cumulative incidence of glaucoma development and progression after corneal transplant, in patients without and with preoperative glaucoma, respectively. Risk factors for glaucoma development and progression were also assessed. RESULTS: Four hundred and thirty-one eyes of 431 patients undergoing PK (113), DALK (17), DSEK (71), DMEK (168), KPro (35) and EK under previous PK (27) with a mean follow-up of 22.9 months were analyzed. The 1-year cumulative incidence for glaucoma development and progression was 28.0% and 17.8% in patients without and with preoperative glaucoma, respectively. In a Cox proportional hazards analysis, DSEK surgery, KPro implantation, average intraocular pressure (IOP) through follow-up and postoperative IOP spikes of ≥30 mmHg were each independently associated with glaucoma development or progression (p < 0.04 for all). CONCLUSIONS: A significant proportion of patients developed glaucoma or exhibited glaucoma progression within 1 year after corneal transplantation. Patient selection for DSEK may partly explain the higher risk for glaucoma in these patients. Postoperative IOP spikes should be minimized and may indicate the need for co-management with a glaucoma specialist.

Updates in SJS/TEN: collaboration, innovation, and community.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.

Posterior Polymorphous Corneal Dystrophy in a Pediatric Population.

PURPOSE: The aim of this study was to evaluate the clinical and topographic features of posterior polymorphous corneal dystrophy (PPCD) in children aged 15 years or younger with a long-term follow-up. Retrospective case series. METHODS: A retrospective chart review of patients who were diagnosed with PPCD at Boston Children's Hospital from 1999 to 2020 was performed. Data collected included age at the time of diagnosis, slit lamp findings, cycloplegic refraction, best-corrected visual acuity, central corneal thickness, specular microscopy, and corneal topography findings whenever available. RESULTS: Twenty-seven eyes of 19 patients were included (11 unilateral and 8 bilateral cases). Ten patients were girls (52.6%). Left eye was affected in 14 eyes. The mean age at the time of diagnosis was 8.5 ± 3.3 years, with a mean follow-up of 5.3 years. In unilateral cases, there was a statistically significant difference in the endothelial cell density (P = 0.01), coefficient variation (P = 0.03), and hexagonality (P = 0.01) between the affected and the contralateral unaffected eyes. The mean best-corrected visual acuity at initial presentation was 0.8 ± 0.2 compared with 0.9 ± 0.08 in unaffected eyes (P = 0.04). The mean astigmatism was higher in the affected eye (+1.7 diopters) compared with (+1.00) the unaffected eye (P = 0.07). At initial presentation, 7 of 27 eyes had amblyopia, which resolved, either partially or completely, in 5 eyes after treatment. CONCLUSIONS: PPCD can present early in children with astigmatism and anisometropic amblyopia. A careful slit lamp examination for children presenting with anisoastigmatism is necessary to diagnose PPCD. Contrary to adults, presentation is often unilateral. Such patients should be followed up regularly with cycloplegic retinoscopy to prevent and treat refractive amblyopia if present.

Corneal stromal deposits in connective tissue disease, a case series.

PURPOSE: We report two cases of refractile, peripheral, corneal stromal deposition in two patients with arterial tortuosity syndrome (ATS) and Ehlers-Danlos syndrome (EDS), two closely related connective tissue diseases (CTDs). OBSERVATIONS: Patient 1: A 21-year-old man with history of ATS and keratoectasia presented with bilateral peripheral corneal neovascularization with numerous whitish brown, refractile, deep stromal opacities that were circumferential along the inferotemporal cornea. After 3 years of follow-up, the corneal deposits did not progress, but the ectasia did, with significant bilateral corneal steepening and thinning for which the patient was recommended to undergo repeat corneal collagen cross linking. Patient 2: A 26-year-old man with presumed diagnosis of EDS presented with numerous whitish brown, refractile, deep stromal opacities that were circumferential along the temporal cornea in the right eye, and superiorly in the left eye. The left eye had a pseudopterygium involving 50% of the cornea. After 2 years of follow-up, the corneal opacities did not progress; however, the patient underwent primary excision of the pseudopterygium and subsequently had conjunctivalization of the entire cornea. The lesions in both cases resembled those seen in Terrien's marginal degeneration. CONCLUSIONS AND IMPORTANCE: Peripheral corneal stromal deposits have never been reported before in EDS or ATS or other connective tissue diseases. This case series may prompt further inquiry and characterization of these findings in patients with CTDs.

Visual function and quality of life in patients with Stevens-Johnson syndrome who received acute protocol-based ocular care.

Purpose: To report visual function and quality of life (VF/QOL) using the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the ocular surface disease index (OSDI) in patients in the chronic phase of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Methods: The NEI-VFQ-25 questionnaire was administered to 15 patients who received protocol-based care in the form of topical medications with or without amniotic membrane transplantation (AMT) for acute SJS/TEN. The scores obtained were compared with scores from a healthy population. The associations between the NEI-VFQ-25 and dry eye symptoms as measured by OSDI questionnaire were also studied. Results: Patients were surveyed at a mean of 4.47 ± 2.22 years after acute SJS/TEN. Eleven patients received AMT in the acute phase. The median best corrected visual acuity at the time of administration of the questionnaire was 20/20. The mean composite NEI-VFQ-25 score was 86.48 ± 12. Patients who received protocol-based treatment in the acute phase of SJS/TEN had comparable NEI-VFQ-25 scores with healthy subjects on all subscales except ocular pain (p = 0.027) and mental health (p = 0.014), which were significantly reduced. The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = -0.75, p = 0.001). Conclusion: A protocol-based management strategy composed of early ophthalmic evaluation, grading based on severity, the use of topical corticosteroids and AMT in the acute phase of SJS/TEN in patients with ocular complications helped preserve the VF/QOL. This study highlights the impact of appropriate management of the ocular complications in the acute phase of SJS/TEN.

Topical cenegermin 0.002% for pediatric neurotrophic keratopathy.

PURPOSE: To evaluate the efficacy and safety of cenegermin 0.002% ophthalmic drops in the management of pediatric neurotrophic keratopathy (NK). METHODS: Retrospective chart review of children under the age of 18 years diagnosed with NK at Boston Children's Hospital/Massachusetts Eye and Ear Infirmary and treated with topical cenegermin 0.002% ophthalmic solution between June 2018 and June 2021 was performed. Data collection included etiology of NK, age at time of initiation of topical cenegermin, laterality, ethnicity, gender, history of previous ocular therapy, pre- and post-therapy best corrected visual acuity, pre- and post-therapy cornea examination, any adverse events from topical cenegermin, associated ocular conditions, and history of ocular surgeries. RESULTS: The current study includes four eyes of four pediatric patients with a mean age of 4.5 ± 2.0 years at the time of initiation of topical cenegermin therapy. The mean time from NK diagnosis until start of topical cenegermin drops was 5.2 ± 4.3 months and mean follow-up time was 15 ± 9.6 months. In all four patients, marked improvement in epitheliopathy was demonstrated after completion of therapy. Best corrected visual acuity was measurable in 3 eyes of 3 patients, and it improved from a mean of 0.07 ± 0.01 to a mean of 0.29 ± 0.26 (P = 0.3). No adverse events related to cenegermin therapy were noted. CONCLUSION: Topical cenegermin was effective in improving corneal healing for pediatric NK.