Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

[Dupilumab-related blepharoconjunctivitis: Recommendations of the CEDRE group. Atopic dermatitis, conjunctivitis and dupilumab: Which management approach?] / Blépharo-conjonctivites sous dupilumab : recommandations du groupe CEDRE. Dermatite atopique, conjonctivites et dupilumab : quelle prise en charge ?

Dupilumab is a recombinant monoclonal IgG4 type antibody which inhibits IL4 and IL13 signaling. It is indicated in moderate to severe atopic dermatitis (AD) in adults and adolescents over 12 years of age. Its side effects include conjunctivitis and blepharoconjunctivitis, affecting between 4.7% and 28% of patients depending on the study. The incidence of conjunctivitis in patients treated with dupilumab for AD appears to be higher than placebo in clinical studies. This increase was not observed in patients treated with dupilumab for asthma or sinonasal polyposis. The risk factors for conjunctivitis in patients with AD are disease severity, pre-existence of conjunctivitis and low concentrations of dupilumab, but the pathophysiology of this disease is poorly understood. A literature search carried out in April and May 2020 showed an increase in the number of publications on the subject, but there are currently no official joint dermatologist-ophthalmologist recommendations for prevention and management. The objective of this article is to provide an overview of the status of this subject, to address the main questions raised by this type of conjunctivitis and to suggest a course of action for starting and continuing treatment with dupilumab in patients with AD, according to the recommendations of the French Ophthalmologist/Dermatologist group CEDRE.

[Outcomes of cataract surgery in patients with Fuchs endothelial corneal dystrophy]. / Chirurgie de cataracte seule chez le patient porteur d'une dystrophie endothéliale de Fuchs.

PURPOSE: While endothelial keratoplasty has become the standard treatment for Fuchs dystrophy, the strategy for first-line surgery in patients with associated cataract is still debated. The purpose of this study was to evaluate the surgical outcomes of eyes with Fuchs endothelial corneal dystrophy (FECD) undergoing phacoemulsification alone, to ascertain preoperative factors that predict the need for endothelial keratoplasty (EK). METHODS: Single-center retrospective study. Cataract surgery alone was performed in 64 eyes of 50 patients with FECD. This decision was made if the patient did not have morning blur, the central corneal thickness (CCT) was below 630 microns, and endothelial cells were visible in the periphery. RESULTS: Mean follow-up was 21 months (range 5-55 months). The mean preoperative CCT was 571±43µm. 6 months after surgery, it was 584±52µm (P=0.12). During follow-up, 14 eyes (22%) required an EK because of poor visual outcome after cataract surgery alone. Mean pre-operative CCT of these eyes (595±23µm) was significantly higher than eyes that did not require EK during follow-up (564±45µm, P=0.022). Over 570 microns, 34% of eyes required an endothelial keratoplasty after the cataract surgery alone. CONCLUSIONS: CCT below 630µm associated with the absence of morning blur are preoperative criteria allowing 78.1% eyes with FECD to obtain good visual outcomes after cataract surgery alone. In these eyes, EK can therefore be avoided while ensuring good results.

[Impact of the Lubrizol Rouen plant fire of September 26, 2019 on ophthalmic emergency room visits]. / Impact de l'incendie de l'usine Lubrizol à Rouen le 26 septembre 2019 sur la fréquentation des urgences ophtalmologiques.

INTRODUCTION: A fire at the Lubrizol chemical factory in Rouen on September 26, 2019 generated a huge column of smoke directed northeast toward the city. As the eye might be particularly affected by the smoke and other toxic emissions from the fire, we assessed the impact of this industrial and ecological disaster on irritative eye surface disease in the week following the accident. MATERIALS AND METHODS: We retrospectively collected the medical data of the patients who presented to the Ophthalmology Emergency Department (OED) of Rouen University Hospital (the only OED open during the days following the accident) during the week following the fire (W1). We compared these data with those of patients who presented during the week before the fire (W-1). We also collected data on patients presenting to the ED in general during W-1 and W1, including the number of visits directly related to the fire. RESULTS: 361 patients presented to the OED during W1 following the fire, compared with 384 in W-1. Of these patients, 83 (23%) had ocular surface disease in W1, versus 76 (20%) in W-1. Conjunctivitis was found in 54 patients in W1 (39 viral, 9 allergic, 6 undetermined) versus 44 in W-1 (27 viral, 12 allergic, 5 undetermined). A dry irritative syndrome was present in 29 patients in W1 versus 32 in W-1. Only 4 patients directly attributed their symptoms to the fire: 2 viral conjunctivitis, 1 allergic conjunctivitis and 1 worried patient (at D2, D5, D7 and D7 following the fire respectively). DISCUSSION: The number of emergency eye consultations did not change in the week following the Lubrizol factory fire (except for a decrease the day of the accident, related to the lock-down). There was a higher number of consultations in W1 for conjunctivitis, mostly viral in appearance and probably not directly related to the fire. The number of consultations for dry irritative syndrome was comparable between the two periods. Despite major media coverage of the event at the national level and a very high level of concern among the population, the fire does not seem to have had an effect on OED activity at Rouen University Hospital, nor on general ED visits. The stay-at-home order on the first day may have had a protective effect, avoiding direct exposure to smoke. The long-term consequences of the soot deposits on the ground as the smoke cloud passed over remain undetermined and are under surveillance. A review of the literature on the ocular consequences of industrial accidents is presented. CONCLUSION: The Ophthalmology Emergency Department did not record increased activity in the week following the Lubrizol Rouen fire, and ocular surface disease did not give rise to more consultations than the week before the fire. This suggests that there was no or minimal immediate ocular toxicity of the smoke from the fire.

[Combined Intense Pulsed Light and low-level light therapy in the treatment of Meibomian gland dysfunction]. / Traitement combiné par lumière intense pulsée et thérapie par lumière de faible niveau dans le dysfonctionnement des glandes de Meibomius.

INTRODUCTION: Meibomian gland dysfunction (MGD) is the most common cause of dry eye syndrome. The goal of this study was to evaluate the efficacy of combined intense pulsed light (IPL) and low-level light therapy (LLLT) in symptomatic MGD. MATERIALS AND METHODS: This retrospective study analyzed data from 30 patients with MGD causing dry eye symptoms not relieved by medical therapy and managed with combined IPL and LLLT. The primary endpoint was the Ocular Score Disease Index (OSDI) score at 1 month and 1 year. Secondary endpoints were visual acuity, intraocular pressure, tear film break-up time, Schirmer's test, Oxford score, and infrared meibographic score at 1 month after the conclusion of treatment. RESULTS: The mean OSDI score decreased from 43±19 to 17±12 (1 month; p<0.0001) and then to 29±11 (12 months; p=0.013); 63% of patients were meibographic grade 2 before versus 7% after treatment (range, 1-4) (p=0.009); 75% of patients were Oxford grade 1 before versus 41% after treatment (p=0.004) (range, 1-3). No significant difference in the other secondary endpoints was noted. CONCLUSION: Over time, IPL therapy in combination with LLLT appears to improve patients with symptomatic MGD resistant to medical therapy.

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus.

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Early symptomatic neurosyphilis and ocular syphilis: A comparative study between HIV-positive and HIV-negative patients.

OBJECTIVES: Since the 2000s, there has been an increase in prevalence of neurosyphilis (NS) and ocular syphilis (OS). As data about symptomatic NS/OS is limited, this study aims to assess the characteristics of symptomatic NS/OS, according to HIV status. METHODS: We compared the clinical and biological presentation of early symptomatic NS/OS and its outcome in HIV-positive and HIV-negative patients. RESULTS: Ninety-six patients (93% men, 49% HIV-positive) were included from 2000 to 2016 in two centers, with 67 (69%) having OS, 15 (16%) NS, and 14 (14%) both. HIV-positive patients were younger (P=0.006) and more likely to be males having sex with males (P=0.00048) or to have a history of syphilis (P=0.01). Among 81 OS, there were 43 posterior uveitis (57%), and bilateral involvement was more common in HIV-positive patients (62% versus 38%, P=0.045). Among 29 NS there were 21 cases of cranial nerve involvement (72%), seven meningitis (24%) and 11 paresthesia (38%). Involvement of the VIIIth cranial nerve was the most common (16 cases). Treponemal tests were more commonly found positive in cerebrospinal fluid in HIV-positive patients (88% versus 76%, P=0.04). Visual acuity (VA) always improved after treatment (initial VA logMAR 0.8±0.8 versus 0.1±0.1 at 3 months), but 32% and 18% of the patients still had neurological or ocular impairment respectively six and 12 months after treatment. Non-treponemal serological reversion was observed in 43/50 patients (88%) at six months. CONCLUSION: HIV infection has no consequence on the outcome of NS and OS. Sequelae are common, emphasizing the importance of prevention, and screening, and questioning enhanced treatment.

Management of ocular involvement in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: french national audit of practices, literature review, and consensus agreement.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) can lead to severe ophthalmologic sequelae. The main risk factor is the severity of the initial ocular involvement. There are no recommendations for ocular management during acute phase.We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. We sent a questionnaire on ocular management practices in SJS/ TEN during acute phase to ophthalmologists and dermatologists. The survey focused on ophthalmologist opinion, pseudomembrane removal, topical ocular treatment (i.e. corticosteroids, antibiotics, antiseptics, artificial tear eye drops, vitamin A ointment application), amniotic membrane transplantation, symblepharon ring use, and systemic corticosteroid therapy for ophthalmologic indication. Nine of 11 centers responded. All requested prompt ophthalmologist consultation. The majority performed pseudomembrane removal, used artificial tears, and vitamin A ointment (8/9, 90%). Combined antibiotic-corticosteroid or corticosteroid eye drops were used in 6 centers (67%), antibiotics alone and antiseptics in 3 centers (33%). Symblepharon ring was used in 5 centers (55%) if necessary. Amniotic membrane transplantation was never performed systematically and only according to the clinical course. Systemic corticosteroid therapy was occasionally used (3/9, 33%) and discussed on a case-by-case basis.The literature about ocular management practice in SJS/ TEN during acute phase is relatively poor. The role of specific treatments such as local or systemic corticosteroid therapy is not consensual. The use of preservatives, often present in eye drops and deleterious to the ocular surface, is to be restricted. Early amniotic membrane transplantation seems to be promising.

[Characteristics and management of Uveitis-Glaucoma-Hyphema syndrome]. / Caractéristiques et prise en charge du syndrome Uvéite-Glaucome-Hyphéma.

INTRODUCTION: Uveitis-Glaucoma-Hyphema syndrome (UGH) is caused by mechanical chafing of anterior segment structures by an intraocular lens, especially an anterior chamber lens. The objective of this study was to characterise the clinical course and risk factors of UGH syndrome at a time when posterior chamber implantation is the gold standard. PATIENTS AND METHODS: This was a retrospective study of 30 cases of UGH syndrome managed between January 2014 and September 2018. Data from the initial clinical examination, the type of implant involved and the clinical management were analysed. RESULTS: Thirty eyes of 28 patients were included. Intra ocular lenses were iris-sutured (15/30, 50 %), in the bag (6/30, 20 %), scleral-fixated (4/30, 13.3 %), in the ciliary sulcus (3/30,10 %) or "in and out" (2/30, 6.7 %). Initial management was medical (18 eyes) or surgical (12 eyes). Surgical procedures were explantation (n=4), IOL repositioning (n=7) or trabeculectomy (n=1). Recurrences occurred with medical treatment (9/18), but not in the surgical group (p=0.02). Ocular hypertension became chronic in 19 cases out of 30 (63.3 %). CONCLUSION: UGH syndrome can be caused by any type of pseudophakic lens. An intraocular lens in the bag should not rule out the diagnosis. Despite the decreasing popularity of anterior chamber intraocular lens implantation, UGH syndrome remains a current condition and must be recognised in order to adapt therapeutic management.

[Panorama of limbal alterations (French translation of the article)]. / Panorama des altérations limbiques cornéennes.

The corneal limbus is a privileged region on the border between two quite different microenvironments, where corneal epithelial stem cells, numerous melanocytes, and antigen-presenting cells are all concentrated within a richly vascularized and innervated stroma. This situation within the ocular surface confers on it the key functions of barrier, epithelial renewal and defense of the cornea. As an immunological crossroads and since the corneoscleral limbus is directly exposed to external insults such as caustic agents, ultraviolet radiation, microbial agents, and allergens, it is the potential site of many tumoral, degenerative or inflammatory pathologies and may progress under certain conditions to limbal stem cell deficiency.

[Tacrolimus ointment in the management of atopic keratoconjunctivitis]. / Tacrolimus pommade dans la prise en charge de la kératoconjonctivite atopique.

INTRODUCTION: Atopic keratoconjunctivitis is associated with eyelid eczema. It may require the use of local corticosteroids which if prolonged can be a source of ocular complications. Tacrolimus is an immunosuppressant used in cutaneous application in atopic dermatitis. The aim of this study was to measure the efficacy and tolerance of tacrolimus 0.1% ointment in palpebral application in atopic keratoconjunctivitis. PATIENTS AND METHODS: This retrospective, single-center study was conducted between June 2014 and February 2017. Patients with atopic keratoconjunctivitis not controlled by first-line medical treatments were included. The primary endpoint was the evolution of functional signs as assessed by the NEI-VFQ25 and OSDI quality of life scores. Secondary endpoints were visual acuity and local corticosteroid use. RESULTS: Among the 18 patients included, the mean age was 37.9±16.8 years. The first follow-up visit was on average 68.3±55.3 days after initiation of treatment. The NEI-VFQ25 score was significantly improved for seven of its sub-scores (P<0.05) and the mean OSDI decreased significantly from 52.3±26.2 to 22.0±27.0 (P<0.001) showing a decrease in eye discomfort. A significant reduction was observed in the number of patients using local corticosteroids. There was no significant change in visual acuity. CONCLUSION: Tacrolimus ointment 0.1% in palpebral application appears to be an effective treatment for the management of atopic keratoconjunctivitis.

[Severe color change in corneal tattoos: Report of 3 cases (French translation of the article)]. / Modification majeure de la couleur des tatouages cornéens à propos de 3 cas.

INTRODUCTION: Corneal tattooing is a noninvasive technique which appears relatively well-tolerated in the medium term. We report the cases of 3 patients with a significant change in the color of their tattoos performed over 5 years previously. PATIENTS AND METHODS: Three patients with a history of intracorneal tattooing several years previously were studied because of a significant change from their initial color. Each patient's file was reviewed with analysis of slit lamp photographs, OCT and specular microscopy. RESULTS: All three patients experienced a significant color change in their tattoos between 5 and 6 years after surgery. The color had changed to golden-brown. DISCUSSION: Retrospective analysis of the components of the tattoo ink found the presence of iron in the black pigment. We believe that pigments composed of iron oxide are transformed into golden-brown ferric iron oxide in the presence of oxygen in the aqueous environment. The presence of moderate corneal edema in these three cases of multioperated patients could explain, in these specific cases, the occurrence of oxidation typically not described. CONCLUSION: Corneal tattooing remains a simple and very interesting technique when partial or total absence of iris causes significant photophobia. However, the significant changes in color that we report more than 5 years later suggest omitting iron from the dyes used for the cornea and limiting its use in cases of limited endothelial prognosis. A long-term evaluation of corneal tattoos appears necessary.

Panorama of limbal changes.

The corneal limbus is a privileged region on the border between two quite different microenvironments, where corneal epithelial stem cells, numerous melanocytes, and antigen-presenting cells are all concentrated within a richly vascularized and innervated stroma. This situation within the ocular surface confers on it the key functions of barrier, epithelial renewal and defense of the cornea. As an immunological crossroads and since the corneoscleral limbus is directly exposed to external insults such as caustic agents, ultraviolet radiation, microbial agents, and allergens, it is the potential site of many tumoral, degenerative or inflammatory pathologies and may progress under certain conditions to limbal stem cell deficiency.

Tacrolimus ointment in the management of atopic keratoconjunctivitis.

INTRODUCTION: Atopic keratoconjunctivitis is frequently associated with atopic eyelid dermatitis. It may require topical steroids, the prolonged use of which may cause ocular complications. Tacrolimus is an immunosuppressant used topically on the skin in atopic dermatitis. The purpose of this study is to evaluate the efficacy and tolerability of tacrolimus 0.1% ointment applied to the eyelids in atopic keratoconjunctivitis. PATIENTS AND METHODS: This is a single center, retrospective study carried out between June 2014 and February 2017. Patients presenting with atopic keratoconjunctivitis uncontrolled by first-line medical treatment were included. The main outcome was change in functional symptoms as evaluated by the NEI-VFQ25 and OSDI quality of life scores. Secondary criteria were visual acuity and topical steroids use. RESULTS: Among the 18 patients included, the mean age was 37.9±16.8years. The first follow-up visit occurred on average 68.3±55.3 days after initiation of treatment. The NEI-VFQ25 score improved significantly for seven of the sub-scores (P<0.05), and the mean OSDI decreased significantly from 52.3±26.2 to 22.0±27.0 (P<0.001), demonstrating a decrease in ocular symptoms. A significant reduction in the number of patients requiring topical steroid treatment was observed. There was no significant change in visual acuity. CONCLUSION: Tacrolimus 0.1% ointment applied to the eyelids appears to be an effective treatment in the management of atopic keratoconjunctivitis.

Severe color change in corneal tattoos: Report of 3 cases.

INTRODUCTION: Corneal tattooing is a noninvasive technique which appears relatively well-tolerated in the medium term. We report the cases of 3 patients with a significant change in the color of their tattoos performed over 5 years previously. PATIENTS AND METHODS: Three patients with a history of intracorneal tattooing several years previously were studied because of a significant change from their initial color. Each patient's file was reviewed with analysis of slit lamp photographs, OCT and specular microscopy. RESULTS: All three patients experienced a significant color change in their tattoos between 5 and 6 years after surgery. The color had changed to golden-brown. DISCUSSION: Retrospective analysis of the components of the tattoo ink found the presence of iron in the black pigment. We believe that pigments composed of iron oxide are transformed into golden-brown ferric iron oxide in the presence of oxygen in the aqueous environment. The presence of moderate corneal edema in these three cases of multioperated patients could explain, in these specific cases, the occurrence of oxidation typically not described. CONCLUSION: Corneal tattooing remains a simple and very interesting technique when partial or total absence of iris causes significant photophobia. However, the significant changes in color that we report more than 5 years later suggest removing iron from the dyes used for the cornea and limiting its use in cases of limited endothelial prognosis. A long-term evaluation of corneal tattoos appears necessary.

Tocilizumab for the treatment of birdshot uveitis that failed interferon alpha and anti-tumor necrosis factor-alpha therapy: two cases report and literature review.

Biotherapies appear as potential drugs for the treatment of inflammatory noninfectious uveitis. In this report, we show that tocilizumab, an anti-IL-6 agent, greatly improved two patients with birdshot chorioretinopathy refractory to conventional immunosuppressive drugs, interferon α2a, and anti-TNFα agents. After a follow-up of 22 months, patients exhibited an improvement of both visual acuity and macular edema. A corticosteroid-sparing effect was achieved in both cases.