Correlation of Corneal Complications with Eyelid Cicatricial Pathologies in Patients with Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Syndrome

doi:10.1016/j.ophtha.2004.11.035

Ophthalmology

Volume 112, Issue 5, May 2005, Pages 904-912

https://doi.org/10.1016/j.ophtha.2004.11.035 Get rights and content

Purpose

To look at the correlation between many factors (time of hospitalization, floppy eyelid syndrome, trichiasis, open lacrimal puncta, symblepharon, and aqueous tear deficiency) and corneal complications in Stevens-Johnson syndrome (SJS).

Design

Observational cases series.

Patients

Clinical data were retrospectively reviewed from 38 patients (32.7±20.1 years old) with SJS (n = 11) and with toxic epidermal necrolysis (TENS) (n = 27) from January 2002 to August 2004. One case report with SJS was included to verify the presence of tarsal/lid margin ulceration at the acute stage.

Methods

The medical history was retrieved regarding presumed causative medications used within 15 days and the duration of hospitalization. Data of the latest photographic documentation and eye examination were compared and correlated in a masked fashion.

Main Outcome Measures

Floppy eyelid, trichiasis, lid margin keratinization, meibomian gland orifice metaplasia, symblepharon, tarsal scar, and corneal complications.

Results

Acute SJS/TENS was characterized by tarsal conjunctival ulceration. Keratinization of the eyelid margin with variable degrees of meibomian gland dysfunction was observed in all cases. Floppy eyelid, trichiasis, partially or totally opened lacrimal punctum, symblepharon, and aqueous tear deficiency were not significantly correlated with corneal complications. In contrast, there was a strong correlation between the severity of eyelid margin and tarsal pathology and the extent of corneal complications (Spearman r, 0.54; P = 0.0005). A multivariable regression analysis also showed that the extent of eyelid and tarsal pathology had a significant effect on corneal complications (coefficient, 0.84; P = 0.006).

Conclusions

Patients with acute SJS/TENS are characterized by severe inflammation and ulceration of the tarsal conjunctiva and lid margins. If left unattended, lid margin keratinization and tarsal scar, together with lipid tear deficiency, contribute to corneal complications because of blink-related microtrauma. Attempts to suppress inflammation and scarring by amniotic membrane transplantation at the acute stage and to prevent microtrauma at the chronic stage are vital to avoid sight-threatening complications.

Section snippets

Patients and Methods

This study was approved by the Institutional Review Board of the Baptist Hospital of Miami and South Miami Hospital to retrospectively review the clinical data of patients with SJS or TENS seen at Ocular Surface Center, Miami, Florida, during the period from January 2002 to August 2004. We included patients with the diagnosis of SJS and TENS on the basis of the criteria previously summarized by Power et al.¹ We also included 1 additional patient with an acute attack of SJS hospitalized in the

Lid Margin and Tarsal Ulceration Without Corneal Involvement and Successful Management by Amniotic Membrane Transplantation in Acute Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Syndrome

A 4-year-old boy, with a medical history of asthma and autism, had skin rashes of the face and neck develop the next day after taking ibuprofen to control fever. On the following day, both eyes were red, and blisters were noted in the mouth, resulting in eating difficulty. He was admitted to a pediatric intensive care unit with a presumptive diagnosis of SJS. The skin rashes affected 9% of the body in the ensuing 3 days of hospitalization. He kept both eyes closed and was treated with topical

Discussion

For SJS/TENS, severe inflammation and ulceration, if allowed to be recalcitrant and chronic, led to scarring (cicatrix). Depending on the site of involvement, such cicatrix may result in ATD (obliterating lacrimal excretory ducts), LTD (obliterating meibomian orifices), fornix shortening, symblepharon, ankyloblepharon, punctal stenosis, trichiasis and entropion. On the bulbar conjunctiva, it may cause squamous metaplasia, ranging from goblet cell loss to frank keratinization.⁸ On the limbus, it

References (19)

W.J. Power et al.
Analysis of the acute ophthalmic manifestations of the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum
Ophthalmology
(1995)
J.S. Kim et al.
Amniotic membrane patching promotes healing and inhibits protease activity on wound healing following acute corneal alkali burn
Exp Eye Res
(2000)
D. Meller et al.
Amniotic membrane transplantation for acute chemical or thermal burns
Ophthalmology
(2000)
T. John et al.
Amniotic membrane in the surgical management of acute toxic epidermal necrolysis
Ophthalmology
(2002)
S.C. Tseng et al.
Possible mechanisms for the loss of goblet cells in mucin-deficient disorders
Ophthalmology
(1984)
V. Puangsricharern et al.
Cytologic evidence of corneal diseases with limbal stem cell deficiency
Ophthalmology
(1995)
A. Schermer et al.
Transient synthesis of K6 and K16 keratins in regenerating rabbit corneal epitheliumkeratin markers for an alternative pathway of keratinocyte differentiation
Differentiation
(1989)
J. Shimazaki et al.
Association of preoperative tear function with surgical outcome in severe Stevens-Johnson syndrome
Ophthalmology
(2000)
S.C.G. Tseng et al.
How does amniotic membrane work?
Ocul Surf
(2004)

There are more references available in the full text version of this article.

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To evaluate the incidence, clinical characteristics, microbiological profile, and therapeutic outcomes of corneal ulcers in individuals with chronic ocular graft-vs-host disease (coGVHD).
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Review of individuals diagnosed with coGVHD following hematopoietic stem cell transplantation (HSCT) who were seen at the Bascom Palmer Eye Institute between May 2010 and November 2021. Baseline demographics, clinical characteristics, microbiological profile, risk factors for corneal ulceration, and treatment outcomes were collected. Etiology was deemed infectious in individuals with a positive culture or appropriate clinical scenario (presence of stromal infiltrate or hypopyon); otherwise, ulcers were presumed to be noninfectious. Treatment success was defined as reepithelialization with infiltrate resolution, and treatment failure as progression to corneal perforation or keratoplasty. Kaplan-Meier survival analysis estimated the incidence of ulceration. Cox regression analyses examined demographic and risk factors. Infectious and noninfectious ulcer groups were compared using 2-way independent t tests, 1-way analysis of variances, and χ² tests, as appropriate.
173 individuals were included (53.7±14.4 years old; 59.0% male). Thirty-three individuals developed an ulcer 74.5±54.3 months after HSCT, with estimated 5- and 10-year incidences of 14% and 30%, respectively. Twenty-two (66.6%) ulcers were deemed infectious (15 microbiologically confirmed, 7 clinically) and 11 (33.3%) were deemed noninfectious. Risk factors for corneal ulceration included Black race (hazards ratio [HR] 2.89, 95% CI 1.30-6.42, P < .01), previous ocular surgery (HR 9.16, 95% CI 3.86-21.72, P < .01), eyelid margin abnormalities (HR 3.44, 95% CI 1.69-6.99, P < .01), and topical steroid use (HR 2.74, 95% CI 1.33-5.62, P < .01). Conversely, contact lens use reduced the risk of corneal ulceration (HR 0.29, 95% CI 0.13-0.66, P < .01). Infectious ulcers had a significantly higher frequency of treatment failure than noninfectious ulcers (57.1% vs 20.0%, P = .04).
Corneal ulceration is a potential complication of coGVHD, with several clinical features identified as risk factors. Infectious ulcers had worse outcomes than noninfectious ulcers.
Clinical Outcome of Amniotic Membrane Transplant in Ocular Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis at a Major Burn Unit
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To analyze the clinical outcome of amniotic membrane transplantation in patients with ocular Stevens–Johnson syndrome/toxic epidermal necrolysis at a major burn unit.
Retrospective, non-randomized interventional study.
A retrospective chart review from April 2014 to January 2022 of 43 patients (85 eyes) at a burn center who underwent amniotic membrane transplantation (AMT) for severe ocular Stevens–Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), or SJS/TEN was performed. Data regarding the clinical course and outcome were obtained. A comparison between the use of cryopreserved AMT rings (cryoAMT) and dehydrated AMT (deAMT) was also assessed.
A total of 85 eyes in 43 patients underwent AMT for severe ocular SJS/TEN. Of the eyes, 72 received deAMT with symblepharon ring, whereas 13 received cryoAMT over the cornea surface. All patients had deAMT placed over the eyelid margins and palpebral conjunctivae and tucked into the fornices. The average best-corrected visual acuity (BCVA) on last follow-up examination was 20/33, 20/30, and 20/34 in all eyes, the cryoAMT group, and the deAMT group, respectively (no significant difference between groups). The most common suspected inciting agent was lamotrigine (17% of all cases). The average long-term complication score was 1.4, with no significant difference between the cryoAMT group (1.6) and the deAMT group (1.4, P = .5). Symblepharon formation was seen more in the cryoAMT group compared to the deAMT group (P < .05).
The use of AMTs in severe ocular SJS/TEN greatly mitigates long-term complications and improves visual outcome. The retrospective nature of this study limits substantial conclusions regarding any significant difference in outcome between AMT treatment methods. Nevertheless, the use of cryopreserved AMT rings has a similar outcome profile compared to use of dehydrated AMTs with symblepharon ring. Further research is needed to evaluate optimal AMT techniques.
Vulvovaginal and ocular involvement and treatment in female patients with Stevens–Johnson syndrome and toxic epidermal necrolysis: A review
2021, International Journal of Women's Dermatology
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious adverse cutaneous drug reactions, characterized by epidermal detachment and mucous membrane involvement. SJS/TEN is more common in female patients, with unique findings in the ocular and vulvar regions. Early recognition and intervention, as well as long-term follow-up, are crucial to prevent devastating scarring and sequelae. This review examines the vulvar and ocular manifestations of SJS/TEN and describes the current treatment recommendations for female patients, requiring close consultation and collaboration among dermatology, ophthalmology, and gynecology.
Lid margin keratinization in Stevens-Johnson syndrome: Review of pathophysiology and histopathology
2021, Ocular Surface
Citation Excerpt :
The median time to the occurrence of this complication was also three months [6,8]. Although the exact etiopathogenesis of LMK has not been clearly elucidated, a number of potential mechanisms have been proposed [5,9]. Likewise, there are very limited studies on the histopathological findings of the lid margins in chronic SJS [10].
Lid margin keratinization (LMK) is a chronic ocular sequela of Stevens-Johnson syndrome (SJS), which causes lid wiper epitheliopathy and progressive ocular surface damage. The exact etiopathogenesis of LMK, however, remains elusive. This review summarizes the potential pathophysiological mechanisms of LMK and describes its histopathological features. A literature search of articles discussing the pathophysiology of LMK in SJS was performed. The possible pathophysiologic mechanisms contributing to LMK, as identified on the literature review, included loss of the muco-cutaneous junction barrier leading to epidermalization, dyskeratosis involving the meibomian gland orifices, altered lid margin microbiome, and de novo squamous metaplasia of the marginal conjunctival epithelium. Based on these mechanisms, the possible sources of keratinized epithelium at the posterior lid margin in SJS could be the adjacent anterior eyelid skin, hyperkeratinized epithelium from the meibomian gland ductal orifices, or the inflamed marginal conjunctiva. The epithelial, sub-epithelial, and stromal changes seen in keratinized posterior lid margins in SJS patients undergoing mucous membrane grafting were also investigated. The findings revealed keratinizing squamous metaplasia of the posterior lid margin accompanied by subepithelial infiltration of helper T cells predominantly on the conjunctival side. The visible meibomian gland orifices had ductal hyperkeratinization and plugging. These findings support a role for inflammation in the pathogenesis of LMK in SJS. Future research can be directed at delineating the pathways that lead to LMK by studying the changes in the lid margin microbiome, and the molecular mechanisms regulating keratinization in the conjunctiva and the meibomian gland orifices in eyes affected by SJS.
Lid-Related Keratopathy in Stevens-Johnson Syndrome: Natural Course and Impact of Therapeutic Interventions in Children and Adults
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To compare the long-term visual outcomes of different management strategies in children and adults with Stevens-Johnson Syndrome (SJS)−induced chronic lid-related keratopathy.
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This study included 705 eyes of 401 patients (81 children and 320 adults) with SJS who presented with chronic lid-related keratopathy between 1990 and 2015. Affected eyes received either conservative therapy [topical medications (n = 363)] or definitive management (n = 342) that included mucous membrane grafting (MMG), prosthetic replacement of the ocular surface ecosystem (PROSE) contact lenses, or both. The primary outcome measure was change in best corrected visual acuity (BCVA) over time. The secondary outcome measure was the odds of developing corneal ulceration or perforation in the first year.
The treatment subgroups were comparable at baseline in terms of BCVA and previous management (P > .10). Over 10 years, children and adults who received conservative therapy lost at least 5 lines of median BCVA and carried a 3 times higher risk of developing corneal ulceration in the first year. Conversely, definitive therapy provided significant benefit by improving median BCVA (P < .0001). In children, MMG was more effective than PROSE (P = .009), whereas PROSE was more effective than MMG in adults (P = .028). However, the combination of MMG followed by PROSE provided the best results in both children and adults (P < .036).
Both MMG and PROSE changed the natural course and helped in preserving and improving vision in eyes with SJS-induced lid-related keratopathy. Regardless of age, those who received both MMG and PROSE had the best long-term visual outcomes.
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: Manuscript no. 2004-43.

: Supported in part by an unrestricted grant from Ocular Surface Research and Education Foundation, Miami, Florida.

: Dr Tseng and his family are more than 5% shareholders of TissueTech, Inc., which owns United States patent nos. 6 152 142 and 6 326 019 on the method of preparation and clinical uses of human amniotic membrane, which is currently distributed by Bio-Tissue, Inc.

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Case reportCorrelation of Corneal Complications with Eyelid Cicatricial Pathologies in Patients with Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Syndrome

Purpose

Design

Patients

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Patients and Methods

Lid Margin and Tarsal Ulceration Without Corneal Involvement and Successful Management by Amniotic Membrane Transplantation in Acute Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Syndrome

Discussion

Ophthalmology

Exp Eye Res

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Differentiation

Ophthalmology

Ocul Surf

Case report
Correlation of Corneal Complications with Eyelid Cicatricial Pathologies in Patients with Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Syndrome