Comparison of the ocular microbiome between chronic Stevens-Johnson syndrome patients and healthy subjects

Abstract

Stevens -Johnson syndrome (SJS) has manifestation through the exfoliation of epidermis and mucosaltissue. Ocular surface is usually affected in acute and chronic stage. The patients are usually suffered from chronic ocular sequelae including symblepharon, limbal stem cell deficiency, etc. Furthermore, ocular microbiome may also be altered in SJS. This is prospective, age and sex matched analytical study which including 20 chronic SJS patients and 20 healthy subjects for specimen collection from inferior conjunctiva for microbiome analysis by conventional cultures and next-Generation Sequencing (nGS) methods. Significant higher proportion of positive-cultured specimen was demonstrated in SJS group (SJS group 60%, healthy 10%, p-value = 0.001). In addition, NGS which providing high-throughput sequencing has demonstrated the greater diversity of microbial species. the higher proportion of pathogenic microorganisms including Pseudomonas spp., Staphylococcus spp., Streptococcus spp., Acinetobacter spp. was shown in SJS group. ocular surface in SJS is usually occupied by more diverse microorganisms with increased proportion of pathogenic species. This condition may affect chronic inflammation and opportunistic infections in SJS group. In order to prevent and treat infection in these patients, appropriate antibiotics based on bacterial examination should be considered as the first-line treatment in the SJS patients.Stevens -Johnson syndrome (SJS) is an abnormal immune-mediated responses stimulated by medications such as sulfonamides, allopurinol, cold medicines including paracetamol 1 and systemic infections caused by virus and mycoplasma. Incidence of SJS is 1.2-6 out of 1,000,000 persons per year 2 . Although the incidence of diseases is low, the mortality rate is high ranging from 1% to 5% 2 . Patients usually present with severe, acute blistering disorders that affect the skin and mucous membranes involving oral mucosa and ocular surface 3 . Ocular involvement has been reported in 25-75% of SJS patients 2 . In the acute phase, patients usually develop conjunctivitis, corneal abrasion, and pseudo-membrane formation. While chronic ocular sequelae develop in 35% of cases, including eyelid irregularity, symblepharon formation, limbal stem cell deficiency (LSCD), and keratinization, leading to poor vision 2 .Recent interests are focused in the change of ocular microbiomes in this devastating disease. Several studies reported alteration of the ocular microbiomes in SJS patients, compared to healthy subjects. In healthy eyes, the most common microorganisms are Staphylococcus coagulase negative, Corynebacterium, and Propionibacterium 4,5 which are mainly gram-positive bacteria colonized in the ocular surface. In SJS, more pathogenic species are found including gram-negative bacteria. Frizon, et al. reported different compositions of microorganisms in SJS patients consisting of 55% of gram-positive cocci, 19% of gram-positive bacilli, and 25% of gram-negative bacilli 4 . They also found that these pathogenic organisms showed...

Strain heterogeneity, cooccurrence network, taxonomic composition and functional profile of the healthy ocular surface microbiome

“…The microbial community populated on the human ocular surface may play an important role in both innate and adaptive immune responses. Although these normal commensal florae can colonize the healthy ocular surface without causing disease, several studies have revealed that alterations in the healthy ocular surface microbiome are associated with some ocular surface diseases, such as trachoma [ 12 ], keratitis [ 13 , 45 , 46 ], conjunctivitis [ 47 ], dry eye [ 48 ], mesangial gland dysfunction [ 49 , 50 ], chronic Stevens-Johnson syndrome [ 51 ], and blepharitis [ 52 ]. Hence, a comprehensive understanding of the composition of the ocular surface microbiome is crucial for the future development of probiotic-based eye treatment drugs.…”

The Ocular Microbiome in Stevens-Johnson Syndrome

“…In our study (5), residual specimens from conventional cultures were extracted for 16s rRNA amplification with V3-V4 regions targeting. After genome products were prepared, analysis of sequences was performed by Illumina miseq platform.…”

Clinical Aspects of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis With Severe Ocular Complications in Brazil

“…Half of the patients had multiple bacterial species in their flora, including pathogenic bacteria such as Enterobacter spp, Serratia nonliquefaciens, Escherichia coli, Morganella morganii, Proteus mirabilis, and Haemophilus spp (22). A more recent study compared the microbiomes from SJS patients to those of healthy subjects using conventional cultures and sequencing methods (24). Positive-cultured specimens were found in 60% of the SJS patients and in only 10% of the healthy subjects (24).…”

“…A more recent study compared the microbiomes from SJS patients to those of healthy subjects using conventional cultures and sequencing methods (24). Positive-cultured specimens were found in 60% of the SJS patients and in only 10% of the healthy subjects (24). Corynebacterium and Streptococcus were the bacteria genera detected most frequently.…”

“…rRNA sequencing confirmed a wider diversity of microbial species and a greater proportion of pathogenic microorganisms in the eyes of SJS patients; the genera detected included Pseudomonas, Staphylococcus, Streptococcus, and Acinetobacter (24). This altered microbiome found in SJS cases is likely associated with severe ocular surface abnormalities, including chronic epitheliopathy and reduction of the mucin layer of the tear film (24). In addition, it has been reported that SJS produces an abnormal innate immune response that may affect the balance between mucosal immunity and microorganism pathogenicity, inducing chronic-recurrent ocular surface inflammation (25).…”