New Grading System for the Evaluation of Chronic Ocular Manifestations in Patients with Stevens–Johnson Syndrome

doi:10.1016/j.ophtha.2006.10.029

Ophthalmology

Volume 114, Issue 7, July 2007, Pages 1294-1302

https://doi.org/10.1016/j.ophtha.2006.10.029 Get rights and content

Purpose

To evaluate and grade the extent and severity of chronic ocular manifestations in Stevens–Johnson syndrome (SJS).

Design

Prospective multicenter case series.

Participants

We enrolled 73 patients (138 eyes) with SJS seen between April 2003 and March 2005 at 3 tertiary referral centers.

Methods

Patients with a confirmed history of SJS and chronic ocular complications that persisted for at least 1 year from the onset of SJS were included. Their detailed medical history and ophthalmic examination results were recorded on an itemized data collection form. Complications were categorized as corneal, conjunctival, and eyelid complications, and 13 components were evaluated and graded on a scale from 0 to 3 according to their severity.

Main Outcome Measures

These were broadly classified as corneal (superficial punctate keratopathy, epithelial defect, loss of the palisades of Vogt, conjunctivalization, neovascularization, opacification, keratinization), conjunctival (hyperemia, symblepharon formation), and eyelid (trichiasis, mucocutaneous junction involvement, meibomian gland involvement, punctal damage) complications.

Results

The most severely affected complication components were loss of the palisades of Vogt (114 eyes; 82.6%) and meibomian gland involvement (102 eyes; 73.9%). Visual acuity in 74 of the 138 eyes (53.6%) was worse than 20/200. The severity of corneal, conjunctival, and eyelid complications was significantly correlated with visual loss. All 13 complications were correlated significantly with logarithm of the minimum angle of resolution (logMAR) visual acuity; the correlation coefficient (R) ranged from 0.359 to 0.810 (P<0.0001); for corneal epithelial defects, R was 0.169 (P = 0.0473). Eyes with a higher total score for the 3 complication categories had poorer vision (R = 0.806; P<0.0001). Multivariate regression analysis showed that corneal neovascularization, opacification, keratinization, and cataracts significantly affected logMAR visual acuity (P<0.0001, P<0.0001, P = 0.0142, P = 0.0375, respectively).

Conclusions

The authors describe a new method for grading the extent and severity of ocular involvement in patients with SJS and demonstrate that the severity of ocular involvement is correlated significantly with the final visual outcome. This new grading system provides a more objective method for evaluating SJS patients and may be adapted for use in other cicatricial ocular surface diseases.

Section snippets

Patients

The 3 ophthalmic centers that participated in this multicenter study are Kyoto Prefectural University of Medicine, Keio University, and National Tokyo Medical Center. All patients with chronic ocular complications from SJS who were referred to these centers between April 2003 and March 2005 were evaluated prospectively in this study. Patients with a confirmed history of SJS and chronic ocular complications that persisted for at least 1 year from the onset of SJS were included. The diagnosis of

Results

A total of 138 eyes of 73 patients from the 3 institutions were included in this study. There were 33 males and 40 females. Their age ranged from 10 to 83 years (mean±standard deviation, 47.9±18.5 years). At disease onset, the patients’ ages ranged from 2 to 69 years (mean±standard deviation, 28.4±18.2 years), and the duration of the illness before seeking consultation at our centers ranged from 1 to 54 years (mean±standard deviation, 18.8±15.5 years). Drugs were the most commonly associated

Discussion

Severe ocular surface disease arising from SJS or TEN is associated with significant visual morbidity.1, 2, 3, 4 The evaluation of ocular complications in these patients is extremely important, because ocular involvement often represents the only long-term complication of SJS. There is currently no established method for evaluating the spectrum of ocular manifestations arising from these diseases. In this study, we detailed the characteristic ocular complications in the chronic stage of SJS and

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Ocular Manifestations and Outcomes in Children With Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Comparison With Adult Patients
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To compare the clinical features and visual outcomes in children and adults with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Retrospective comparative case series.
This retrospective study included 280 eyes of 140 patients (35 children and 105 adults) with SJS/TEN treated between 2010 and 2020. The primary outcome measures were the final best-corrected visual acuity (BCVA) and severity of dry eye. The secondary outcome measure was the medical and surgical therapies used.
Among 64 eyes of children recruited in the study, acute ocular involvement was found in 58 eyes (90.6%). The chronic score in pediatric patients was significantly higher than that in adult patients (P = .004). The use of antibiotics/nonsteroidal anti-inflammatory drugs (NSAIDs) and Mycoplasma infection were the more common etiologies in children. In all, 75% of eyes in children maintained a visual acuity of 20/40 or better at a mean follow-up time of 4.3 years. The severity of dryness was comparable between the child and adult groups. The proportion of eyes undergoing amniotic membrane and oral mucosa transplantation was significantly higher in children than in adults in the chronic stage, reflecting that children exhibit much more severe complications.
Although pediatric SJS/TEN patients have more severe ocular complications than adults, most children maintain long-term good vision. Early intervention and aggressive treatment help to preserve vision.
Topical Betamethasone Treatment of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis with Ocular Involvement in the Acute Phase
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To clarify the importance of administering topical steroids for the treatment of Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) with ocular involvement in the acute phase.
Retrospective case series.
Using the medical records of acute SJS/TEN patients treated at the Kyoto Prefectural University of Medicine Hospital, Kyoto, Japan, between July 2006 and July 2017, the ocular findings, topical steroid dosage, systemic steroid dosage, and ocular sequelae were retrospectively examined. The level of cytokines in tear fluid and serum samples was also analyzed.
This study involved 13 cases. In 10 cases in whom the clinical courses were recorded before the start of steroid therapy, the mean acute ocular severity score (AOSS: 3 = very severe; 2 = severe; 1 = mild; 0 = none) was 2.8 ± 0.4 points in the severest phase. The mean systemic steroid dose after steroid pulse therapy was 694 ± 386 mg and the mean topical steroid (0.1% betamethasone eye drop and ointment) dose was 13.4 ± 3.3 times daily in the severest phase. Analysis of cytokine levels of 4 cases showed that a cytokine storm occurred in the tear fluid after the steroid pulse therapy. At final follow-up, 16 eyes of 8 patients had a logMAR visual acuity of ≤0, and no serious ocular sequelae were observed.
In patients with SJS/TEN, ocular surface inflammation remains strong even after systemic inflammation has improved post steroid pulse therapy, thus suggesting that both systemic and topical steroid therapy should be administered appropriately.
Insights into the clinical development of regenerative medical products through a comparison of three cell-based products recently approved for limbal stem cell deficiency
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Three regenerative medical products for limbal stem cell deficiency (LSCD), a rare and intractable ocular surface disease, have recently been approved in Japan. To our knowledge, this is the first time multiple stem-cell-based medical products have been approved for the same ocular disease. Development plans and study designs for each product differ, resulting in differences in indications. Since cell-based products have a heterogeneous formulation and often target rare diseases, they require a flexible approach to development. This review article describes the status and prospects of the clinical development of regenerative medical products by summarizing the issues of the three products from the Pharmaceuticals and Medical Devices Agency (PMDA) standpoint. Implementing stem cell-based products is challenging, requiring scientific and flexible review by regulatory authorities. To overcome these issues in the development process, developers and regulatory authorities need to communicate and fully discuss study protocols from the early stage of development.
Clinical Trial of Autologous Cultivated Limbal Epithelial Cell Sheet Transplantation for Patients with Limbal Stem Cell Deficiency
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To confirm the efficacy and safety of Good Manufacturing Practice (GMP)-compliant autologous cultivated limbal epithelial cell sheets in government-controlled clinical trials that adhered to Good Clinical Practice stipulations for patients with unilateral limbal stem cell deficiency (LSCD).
A prospective, multicenter, open-label, uncontrolled, single-arm clinical trial.
Ten consecutive eyes of 10 patients with unilateral LSCD were followed for 2 years after surgery. Preoperative LSCD stage was IIB in 4 eyes and III in 6 eyes.
A limbal tissue biopsy was obtained from the healthy eye, after which limbal stem cells were dissociated and cultivated on temperature-responsive culture surfaces. All cell sheets were fabricated in a GMP-grade facility under established standard operating procedures. Cell sheets were evaluated using defined shipment criteria before transplantation, and only those that met the criteria were used. The cell sheet was transplanted onto each of the patients' diseased eye after removing the conjunctival scar tissue that covered the corneal surface. The severity of LSCD was determined according to a staging method agreed on by global consensus, with eyes evaluated as being in stages IA–C representing successful corneal epithelial reconstruction. Diagnosis and staging of LSCD were determined by the trial's Eligibility Judgment Committee and Effect Assessment Committee using slit-lamp photographs including fluorescein staining. Both committees comprised 2 or 3 third-party cornea specialists, who were provided with information anonymously and randomly.
Corneal epithelial reconstruction rate was the primary end point.
Corneal epithelial reconstruction was successful in 6 of 10 eyes (60%) 1 year postoperatively and was significantly higher than the 15% clinically significant efficacy rate achieved by allogeneic limbal transplantation. The reconstruction rate was 70% of eyes 2 years postoperatively. Additionally, improvements in visual acuity were noted in 50% and 60% of eyes at 1 and 2 years, respectively. No clinically significant transplantation-related adverse events were observed.
The efficacy and safety of cultivated limbal epithelial cell sheet transplantation were thus confirmed, and the cell sheet, named “Nepic,” is now approved as a cellular and tissue-based product in Japan.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
Proprietary or commercial disclosure may be found after the references.
Successful restoration of corneal surface integrity with a tissue-engineered allogeneic implant in severe keratitis patients
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Corneal diseases are among the main causes of blindness, with approximately 4.6 and 23 million patients worldwide suffering from bilateral and unilateral corneal blindness, respectively. The standard treatment for severe corneal diseases is corneal transplantation. However, relevant disadvantages, particularly in high-risk conditions, have focused the attention on the search for alternatives.
We report interim findings of a phase I-II clinical study evaluating the safety and preliminary efficacy of a tissue-engineered corneal substitute composed of a nanostructured fibrin-agarose biocompatible scaffold combined with allogeneic corneal epithelial and stromal cells (NANOULCOR). 5 subjects (5 eyes) suffering from trophic corneal ulcers refractory to conventional treatments, who combined stromal degradation or fibrosis and limbal stem cell deficiency, were included and treated with this allogeneic anterior corneal substitute.
The implant completely covered the corneal surface, and ocular surface inflammation decreased following surgery. Only four adverse reactions were registered, and none of them were severe. No detachment, ulcer relapse nor surgical re-interventions were registered after 2 years of follow-up. No signs of graft rejection, local infection or corneal neovascularization were observed either. Efficacy was measured as a significant postoperative improvement in terms of the eye complication grading scales. Anterior segment optical coherence tomography images revealed a more homogeneous and stable ocular surface, with complete scaffold degradation occurring within 3–12 weeks after surgery.
Our findings suggest that the surgical application of this allogeneic anterior human corneal substitute is feasible and safe, showing partial efficacy in the restoration of the corneal surface.
Marsupialization of conjunctival inclusion cyst in Stevens-Johnson syndrome
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To present the application and efficacy of marsupialization for the treatment of conjunctival inclusion cyst in Stevens-Johnson syndrome.
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After the operation, the conjunctival sacs were deepened and the average depth was 4.0 mm. Follow-ups which ranged from 7 months to 3 years (19 months on average, the median was 14 months) showed that in four eyes the conjunctival sacs were significantly deepened and in one eye it became shallow.
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: Manuscript no. 2006-570.

: The authors have no financial interest in this work.

: Supported in part by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan, and grants from the Ministry of Health, Labor, and Welfare, Tokyo, Japan.

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Original ArticleNew Grading System for the Evaluation of Chronic Ocular Manifestations in Patients with Stevens–Johnson Syndrome

Purpose

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Patients

Results

Discussion

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Dermatol Clin

Ophthalmology

Am J Ophthalmol

Ocular aftermath of Stevens-Johnson syndrome

Arch Ophthalmol

The ocular complications of erythema multiforme (Stevens Johnson syndrome) and their management

Trans Ophthalmol Soc U K

Long-term ocular complication of Stevens-Johnson syndrome

Clin Pediatr (Phila)

Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study

Arch Dermatol

Stevens-Johnson syndrome and toxic epidermal necrolysis are severity variants of the same disease which differs from erythema multiforme

J Dermatol

Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes

Arch Dermatol

Original Article
New Grading System for the Evaluation of Chronic Ocular Manifestations in Patients with Stevens–Johnson Syndrome