Long-term Progression of Ocular Surface Disease in Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis

Abstract

Purpose: To investigate the details of the long-term progression of ocular surface cicatrization in eyes with ocular sequelae caused by Stevens–Johnson syndrome (SJS)/toxic epidermal necrosis (TEN). Methods: In 105 eyes of 66 patients with SJS/TEN, the severity of ocular sequelae was retrospectively evaluated using an ocular surface grading score (OSGS) at 2 time points separated by a greater than 5-year interval. The OSGS included 7 ocular surface components (conjunctivalization, neovascularization, opacification, keratinization, symblepharon, and upper/lower conjunctival-sac shortening) evaluated into grades 0 to 3 (maximum total OSGS: 21), with the worsening of each component and total OSGS evaluated at the greater than 5-year interval. Moreover, we evaluated whether upper-tarsus and lid-margin scarring are factors that affect ocular surface cicatrization progression. Results: In 35 (33.3%) of 105 eyes, the total OSGS worsened during the follow-up period. Partial conjunctivalization (score 1–2) progressed more frequently to total conjunctivalization (score 3) than to no conjunctivalization (score 0) (OR [95% CI]; 5.6 [1.6–20.3]). Partial keratinization (score 1–2) also had a high risk of progression into total keratinization (41.0 [6.3–266.5]). In all cases, keratinization progressed only in the eyes with total conjunctivalization (conjunctivalization score 3). Severity of upper-tarsus scarring or lid-margin scarring affected the worsening of the total OSGS. Conclusions: In 66 patients with chronic-phase SJS/TEN, ocular surface cicatrization progressed in 33.3% of the 105 eyes during the long-term follow-up period of over 5 years. More than 50% of the partial conjunctivalization eyes progressed toward total conjunctivalization. The partial keratinization eyes had a high possibility of progressing to total keratinization; that is, the so-called “end-stage” status.

Predictive biomarkers for the progression of ocular complications in chronic Stevens-Johnson syndrome and toxic Eeidermal necrolysis

“…IL-8 was significantly upregulated in the SJS/TEN cases with conjunctivalization, neovascularization, or opacification. In our previously study investigating the progression of 7 components of the ocular surface in chronic SJS/TEN cases, our findings revealed that there is a significant correlation between conjunctivalization, neovascularization, and opacification 15 . It has previously been reported that IL-8 promotes corneal neovascularization in mouse models 17 , 18 .…”

“…Moreover, IP-10 was significantly downregulated in SJS/TEN cases with conjunctivalization and neovascularization. As stated above, conjunctivalization is strongly correlated with neovascularization 15 . It was previously reported in a corneal-neovascularization mouse-model study that IP-10 acts as an inhibitor of neovascularization 23 .…”

“…The SJS/TEN patients were divided into two groups, i.e., ‘mild' and ‘severe', according to our previously reported OSGS 27 , 28 . Briefly, in accordance with our modified OSGS 15 , the following 7 ocular-surface components were examined in all enrolled SJS/TEN patients: (1) conjunctivalization, (2) neovascularization, (3) opacification, (4) keratinization, (5) symblepharon, and (6) upper and (7) lower conjunctival sac shortening. Each component was graded on a scale from 0 to 3, depending on the severity of involvement.…”

“…Recent studies have reported that SJS/TEN-related SOC progress in the chronic phase 15 , 16 , however, the biomarkers to predict the progression have yet to be elucidated. Moreover, the management of those SOC differs depending on each medical facility, so it is important to elucidate the specific predictive biomarkers to help guide treatment.…”

Matrix Metalloproteinase-9 and Topical Cyclosporine Are Associated with Conjunctival Microbiota Culture Positivity in Korean Patients with Stevens-Johnson Syndrome

“…[1,2] Acute and chronic ocular manifestations may lead to chronic sequelae of limbal stem cell de ciency, corneal conjunctivalization, persistent epithelial defect, lid margin keratinization, symblepharon, ankyloblepharon etc. [3][4][5] Ocular involvement in SJS can be managed with surgical interventions and several medical therapies which includes topical corticosteroids or cyclosporine. [4,6] An innumerable amount of microbial communities inhabit the human body including the ocular surface, especially the conjunctiva.…”