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Vernal keratoconjunctivitis (VKC) is a chronic severe ocular allergic inflammation mostly observed in children and young adults. The ocular manifestations are the expression of multifactorial immune mechanisms that generally have a good prognosis, however long-term inflammation may remarkably reduce the visual function due to complications and poor therapeutic responses.

IMPORTANCE: Pediatric blepharokeratoconjunctivitis (PBKC) is a chronic, sight-threatening inflammatory ocular surface disease. Due to the lack of unified terminology and diagnostic criteria, nonspecific symptoms and signs, and the challenge of differentiation from similar ocular surface disorders, PBKC may be frequently unrecognized or diagnosed late. OBJECTIVE: To establish a consensus on the nomenclature, definition, and diagnostic criteria of PBKC. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study used expert panel and agreement applying the non-RAND modified Delphi method and open discussions to identify unified nomenclature, definition, and definitive diagnostic criteria for PBKC. The study was conducted between September 1, 2021, and August 14, 2022. Consensus activities were carried out through electronic surveys via email and online virtual meetings. RESULTS: Of 16 expert international panelists (pediatric ophthalmologists or cornea and external diseases specialists) chosen by specific inclusion criteria, including their contribution to scientific leadership and research in PBKC, 14 (87.5%) participated in the consensus. The name proposed was “pediatric blepharokeratoconjunctivitis,” and the agreed-on definition was “Pediatric blepharokeratoconjunctivitis is a frequently underdiagnosed, sight-threatening, chronic, and recurrent inflammatory eyelid margin disease associated with ocular surface involvement affecting children and adolescents. Its clinical spectrum includes chronic blepharitis, meibomitis, conjunctivitis, and corneal involvement ranging from superficial punctate keratitis to corneal infiltrates with vascularization and scarring.” The diagnostic criteria included 1 or more suggestive symptoms accompanied by clinical signs from 3 anatomical regions: the eyelid margin, conjunctiva, and cornea. For PBKC suspect, the same criteria were included except for corneal involvement. CONCLUSIONS AND RELEVANCE: The agreements on the name, definition, and proposed diagnostic criteria of PBKC may help ophthalmologists avoid diagnostic confusion and recognize the disease early to establish adequate therapy and avoid sight-threatening complications. The diagnostic criteria rely on published evidence, analysis of simulated clinical cases, and the expert panel’s clinical experience, requiring further validation with real patient data analysis.

Background/Objectives: Cyclosporine A cationic ophthalmic emulsion (CsA CE) was evaluated in paediatric and adolescent patients with vernal keratoconjunctivitis (VKC) in the NOVATIVE (NCT00328653) and VEKTIS (NCT01751126) trials. The similarity of these studies permitted pooled assessment of the effect of CsA CE on corneal damage as well as safety and tolerability. Subjects/Methods: Pooled outcomes were assessed for the first 28 days of treatment. In NOVATIVE, 118 patients were randomised to 4 times daily (QID) CsA CE 0.05%, 0.1%, or vehicle eye drops. In VEKTIS, 169 patients were randomised to CsA CE 0.1% QID or twice daily (BID) or vehicle. For these analyses, treatment groups comprised: (1) pooled CsA CE 0.1% QID arms (high-dose; n= 96); (2) pooled CsA CE 0.05% QID arm from NOVATIVE and CsA CE 0.1% BID data from VEKTIS (low-dose; n= 93); and (3) pooled vehicle QID arms (vehicle; n= 98). Results: Changes from baseline to day 28 (mean ± standard deviation) in corneal fluorescein staining (CFS) scores for CsA CE high-dose, low-dose, and vehicle groups were −1.6 ± 1.47 (95% CI: −0.9, −0.1; p= 0.0124 vs vehicle), −1.7 ± 1.39 (95% CI: −1.1, −0.3; p= 0.0015 vs vehicle), and −1.0 ± 1.55, respectively. Adverse events (AEs) of any type were reported in 37.5%, 34.4%, and 37.8% of the high-dose, low-dose, and vehicle groups, respectively. Most were mild or moderate in severity. Conclusions: CsA CE significantly decreased corneal damage and was safe and well tolerated in patients with VKC. These data support CSA CE as a treatment option for the management of VKC.

The mission of the Tear Film & Ocular Surface Society (TFOS) is to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Fundamental to fulfilling this mission is the TFOS Global Ambassador program. TFOS Ambassadors are dynamic and proactive experts, who help promote TFOS initiatives, such as presenting the conclusions and recommendations of the recent TFOS DEWS II™, throughout the world. They also identify unmet needs, and propose future clinical and scientific solutions, for management of ocular surface diseases in their countries. This meeting report addresses such needs and solutions for 25 European countries, as detailed in the TFOS European Ambassador meeting in Rome, Italy, in September 2019.

To determine neurotrophic keratitis (NK) frequency, etiologies and prognostic factors, and evaluate the outcome of its management.

Background/aimsTo describe the ocular manifestations associated with epidermolysis bullosa acquisita (EBA).MethodsThis retrospective study was conducted at a tertiary bullous disease clinic. Consecutive patients were enrolled with biopsy proven diagnosis of EBA, with ocular involvement and a follow-up of at least 36 months. A multidisciplinary team of dermatologists, ENT specialists and ophthalmologists evaluated all patients. Immunological workup included direct (including immune-electron microscopy) and indirect immunofluorescence. Ophthalmological examination included best-corrected visual acuity (BCVA) and slit-lamp examination with grading of conjunctival fibrosis using the Tauber classification.ResultsNine patients (five females, four males) were included. The mean age at diagnosis was 32 years (range 1–52 years). Follow-up ranged from 3 to 18 years (mean 10.7 years). Conjunctival fibrosis was present in all affected eyes and was stage III or greater in 60% of patients. Eight patients (14 eyes) had corneal involvement most frequently associated with trichiasis-associated mechanical irritation or extensive cicatrising conjunctivitis. Corneal lesions developed on three eyes of three patients without eyelid disease or severe fibrosis or any identifiable triggering factor. Eyelids were affected in six patients, with trichiasis being the most common feature (affecting three patients, four eyes). Corneal-related blindness occurred in at least one eye in 44% of the patients.ConclusionEBA may be associated with devastating ocular manifestations. Most patients develop severe cicatrising conjunctivitis. A subset of patients may present with isolated corneal lesions. Further studies are warranted to assess the effects of systemic treatments on the evolution of ocular manifestations.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajo.2009.07.006 Byline: Benedicte Tougeron-Brousseau (a), Agnes Delcampe (a)(b), Julie Gueudry (a), Lisa Vera (a), Serge Doan (b), Thanh Hoang-Xuan (b), Marc Muraine (a) Abstract: To describe the therapeutic benefits of scleral lenses in the management of severe ocular surface disease attributable to toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). Author Affiliation: (a) Ophthalmology Department, Charles Nicolle Hospital, CHU de Rouen, Rouen, France (b) Ophthalmology Department, Bichat Hospital, AP-HP, Paris, France Article History: Accepted 11 July 2009 Article Note: (footnote) Supplemental Material available at AJO.com.

Background/aimsDry eye disease (DED) is categorised by pathophysiology as aqueous deficient dry eye (ADDE), evaporative dry eye (EDE) or mixed. Treatment should be tailored to DED pathophysiology, but this is challenging to determine. This Delphi consultation aimed to categorise and weight signs and symptoms to help identify the evaporative or aqueous deficient DED origin.MethodsA panel of French DED experts created an initial list of 77 DED signs and symptoms. In a Delphi consultation, experts categorised items by DED pathophysiology. Likert scoring was used to indicate whether items were strongly or moderately indicative of ADDE or EDE. Items could also be judged non-applicable to DED, with the opportunity to suggest alternative diagnoses.ResultsExperts attributed 19 items (of which 11 were strongly indicative) to a pathophysiology of EDE and 12 items (of which four were strongly indicative) to ADDE. Items scored strongly indicative with agreement >90% for EDE were previous chalazia, rosacea/rhinophyma, telangiectasias of eyelid margin and thick non-expressible meibomian gland secretions, and for ADDE were Sjo¨gren syndrome or associated disease, and Schirmer <5 mm after 5 min (without anaesthesia). Seventeen items indicated neither pathophysiology and 18 items were found to be suggestive of alternative diagnoses.ConclusionsThis Delphi consultation categorised signs and symptoms, using an innovative weighting system to identify DED pathophysiology. An algorithm integrating the weighting of each sign and symptom of an individual patient would be valuable to help general ophthalmologists to classify the DED subtype and tailor treatment to DED underlying mechanism.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajo.2006.09.058 Byline: Serge Doan, Eric E. Gabison, Sylvia Nghiem-Buffet, Olivia Abitbol, Damien Gatinel, Thanh Hoang-Xuan Abstract: To assess the visual outcome of childhood blepharokeratoconjunctivitis. Author Affiliation: Department of Ophthalmology, Bichat Hospital and Fondation A. de Rothschild, Paris, France. Article History: Accepted 22 September 2006

Purpose This study compared the efficacy and safety of hyaluronic acid (HA)-trehalose, a new eyedrop containing trehalose (a natural bioprotectant) and HA, to an established formulation containing only HA.Methods This was a phase III, randomized, active-controlled, investigator-masked, multicenter study in France and Tunisia. In all, 105 adult patients (≥18 years) with moderate to severe dry eye disease (DED) received either HA-trehalose (n = 52) or HA (n = 53) 3-6 times per day for 84 days. The primary efficacy variable was the Oxford grading score at day 35. A questionnaire on dry eye and symptoms, Schirmer test, tear break-up time, conjunctival hyperemia, and global performance were assessed as secondary efficacy criteria at baseline, day 35, and day 84. Safety assessments were standard.Results Noninferiority of HA-trehalose to HA for keratoconjunctivitis sicca assessed by Oxford grading score was demonstrated at day 35. For the secondary efficacy parameters, reductions in dry eye questionnaire classes of none or mild at day 84, dry eye symptoms of stinging, itching, and blurred vision at day 35, and investigator (days 35 and 84) and patient assessments (day 35) of global performance were significantly better for HA-trehalose. There were no clinically meaningful differences between groups for the other secondary criteria. Both treatments were well-tolerated, and there were fewer ocular symptoms upon instillation and fewer adverse events for HA-trehalose than for HA.Conclusions Hyaluronic acid-trehalose is effective and safe, with better patient satisfaction, than existing HA-only eyedrops particularly from the first month of treatment, and offers a therapeutic advancement in the treatment of moderate to severe DED.

PurposeManagement of severe and refractory Mooren's ulcers is challenging as it encompasses tectonic surgical treatment and aggressive immunosuppressive therapies. Efficacy of rituximab in the management of severe Mooren's ulcers has never been reported.MethodsFive patients (six eyes) from the Cornea and External Disorders department at the Rothschild Ophthalmologic Foundation (Paris, France) were treated for severe Mooren's ulcer unresponsive to conventional treatments between 2008 and 2016. Conventional treatment included topical steroid and ciclosporin 2%, high doses of systemic corticosteroids and/or cyclophosphamide and conjunctival resection with amniotic membrane graft. These patients received two infusions of 1000 mg of rituximab at 2 weeks interval. Epithelial healing, inflammation, additional surgery, systemic corticosteroids and rituximab-related side effects were reported.ResultsThe mean follow-up was 46.8 months. Following rituximab treatment, we observed a complete healing of Mooren's ulcer within 2 weeks in all patients. Peripheral lamellar keratoplasty was associated when peripheral corneal perforation occurred (5/6 affected corneas). Systemic corticosteroids had been discontinued in all patients. Two recurrences occurred 13 and 53 months after the first rituximab infusion and where successfully treated with a new infusion. No rituximab-related adverse events were reported.ConclusionsRituximab was effective in the management of severe Mooren's ulcers and could be an alternative to cyclophosphamide. Additional studies should assess the role of this biotherapy in the management of immunological corneal ulcer.

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitroand in vivoas a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure.

BACKGROUND: Mucous membrane pemphigoid (MMP) still represents a potentially life- and sight-threatening disease. In a subset of patients with severe MMP, conventional immunosuppressants are ineffective or contraindicated. OBSERVATIONS: Twenty-five patients with severe refractory MMP, including 5 with mucous membrane–dominant epidermolysis bullosa acquisita, received 1 or 2 cycles of rituximab (375 mg/m2 weekly for 4 weeks). Twenty-one of the patients were receiving concomitant therapy with dapsone and/or sulfasalazine therapy, which was maintained during rituximab cycles. Complete responses in all affected sites (ocular and/or extraocular) were obtained in 17 patients (68%) by a median time of 12 weeks after the first cycle, and 5 additional patients responded completely after a second cycle, yielding an 88% complete response rate. In all but 1 of the 10 patients with ocular lesions, their eyes became noninflammatory within a mean of 10 weeks. Among the 3 patients (12%) who developed severe infectious complications, 2 (8%) died; they had been receiving concomitant conventional immunosuppressants and high-dose corticosteroids and were hypogammaglobulinemic. Treatment with immunosuppressants was discontinued for all other patients, and no other infection was observed. Ten patients experienced relapse after a mean of 4 (range, 1-16) months after achieving complete responses. CONCLUSIONS: Rituximab appears to have rapid and dramatic efficacy in patients with severe, refractory MMP. The occurrence of severe infections in patients receiving concomitant conventional immunosuppressants supports using rituximab without other immunosuppressants. Controlled prospective studies are warranted to define an optimal treatment protocol.

PURPOSE:To describe a 40-year-old woman who complained of visual loss in her left eye 3 days after an uneventful bilateral myopic refractive surgery by small incision lenticule extraction (SMILE).METHODS:Case report.RESULTS:A 4 × 5 mm anterior central stromal infiltration was observed with moderate pain associated with decreased corneal sensitivity and neither discharge nor fluorescein staining. Bacterial and fungal smears and cultures from the SMILE interface were negative and local antibiotic ineffective. She was subsequently treated with peribulbar dexamethasone injections and oral valacyclovir. Corneal infiltration disappeared progressively, replaced by fibrotic stromal scarring. Optical coherence tomography displayed stromal hyperreflectivity mostly located above the lenticule cut with slight involvement of posterior stroma. In vivo confocal microscopy demonstrated activated keratocytes and highlighted the lack of subbasal corneal nerves in her left eye contrasting with her right eye.CONCLUSIONS:Stromal herpetic keratitis could be considered a potential differential diagnosis to this atypical lamellar keratitis after a SMILE procedure.[[J Refract Surg.2016;32(12):855–857.]

Les pemphigoïdes des muqueuses (PM) sont des maladies bulleuses auto-immunes rares aux complications fibrosantes parfois graves, voire mortelles. Le traitement des formes sévères par immunosuppresseurs (IS) est souvent insuffisant pour contrôler la maladie. Nous présentons une large série rétrospective de PM traitées par rituximab (RTX) avec suivi au long cours.

Le dupilumab, anticorps monoclonal inhibant la signalisation des interleukines 4 et 13 est un traitement efficace dans la dermatite atopique modérée à sévère. La conjonctivite est un effet secondaire fréquent sous dupilumab, notamment chez les patients présentant au préalable une kérato-conjonctivite atopique. Cet effet secondaire représente un défi thérapeutique pour le dermatologue, amenant parfois à interrompre le traitement malgré une bonne efficacité cutanée.