N-palmitoyl-D-glucosamine, a Natural Monosaccharide-Based Glycolipid, Inhibits TLR4 and Prevents LPS-Induced Inflammation and Neuropathic Pain in Mice.

Toll-like receptors (TLRs) are key receptors through which infectious and non-infectious challenges act with consequent activation of the inflammatory cascade that plays a critical function in various acute and chronic diseases, behaving as amplification and chronicization factors of the inflammatory response. Previous studies have shown that synthetic analogues of lipid A based on glucosamine with few chains of unsaturated and saturated fatty acids, bind MD-2 and inhibit TLR4 receptors. These synthetic compounds showed antagonistic activity against TLR4 activation in vitro by LPS, but little or no activity in vivo. This study aimed to show the potential use of N-palmitoyl-D-glucosamine (PGA), a bacterial molecule with structural similarity to the lipid A component of LPS, which could be useful for preventing LPS-induced tissue damage or even peripheral neuropathies. Molecular docking and molecular dynamics simulations showed that PGA stably binds MD-2 with a MD-2/(PGA)3 stoichiometry. Treatment with PGA resulted in the following effects: (i) it prevented the NF-kB activation in LPS stimulated RAW264.7 cells; (ii) it decreased LPS-induced keratitis and corneal pro-inflammatory cytokines, whilst increasing anti-inflammatory cytokines; (iii) it normalized LPS-induced miR-20a-5p and miR-106a-5p upregulation and increased miR-27a-3p levels in the inflamed corneas; (iv) it decreased allodynia in peripheral neuropathy induced by oxaliplatin or formalin, but not following spared nerve injury of the sciatic nerve (SNI); (v) it prevented the formalin- or oxaliplatin-induced myelino-axonal degeneration of sciatic nerve. SIGNIFICANCE STATEMENT We report that PGA acts as a TLR4 antagonist and this may be the basis of its potent anti-inflammatory activity. Being unique because of its potency and stability, as compared to other similar congeners, PGA can represent a tool for the optimization of new TLR4 modulating drugs directed against the cytokine storm and the chronization of inflammation.

Real-world evidence of dupilumab efficacy and risk of adverse events: A systematic review and meta-analysis.

BACKGROUND: Dupilumab, the first biological drug to be approved for the treatment of moderate to severe atopic dermatitis in adolescents and adults, has shown good efficacy and safety in clinical trials. OBJECTIVE: To evaluate real-world data on the efficacy and safety of dupilumab in atopic dermatitis. METHODS: PubMed and EMBASE were searched for observational studies with data on efficacy, drug survival, and safety of dupilumab for the treatment of atopic dermatitis. Primary outcomes were mean percentage change in Eczema Area and Severity Index (EASI) score and proportion of atopic dermatitis patients achieving 50%, 75%, and 90% improvement in EASI score after dupilumab therapy. RESULTS: Twenty-two unique studies encompassing 3303 atopic dermatitis patients were included. After 16 weeks of dupilumab therapy, the pooled proportion of patients achieving 50%, 75%, and 90% EASI score improvement was 85.1%, 59.8%, and 26.8%, respectively, and the weighted mean reduction in EASI score was 69.6%. Conjunctivitis was the most common adverse event, reported in a pooled proportion of 26.1%. LIMITATIONS: Limited data in terms of size and follow-up time were available. CONCLUSION: Real-world data show that dupilumab is a successful and well-tolerated therapy for atopic dermatitis, but ocular adverse events commonly occur. Registries are needed to monitor for adverse events.

Dupilumab-Associated Ocular Surface Disease: Clinical Characteristics, Treatment, and Follow-Up.

PURPOSE: A consecutive case series of patients with dupilumab-associated ocular surface disease (DAOSD) that describes common ocular symptoms and signs, proposes a symptom disease severity grading system, and describes treatment strategies of DAOSD patients was evaluated. METHODS: A retrospective chart review of patients with concomitant dupilumab-treated atopic dermatitis and DAOSD with ophthalmic evaluation between January 2014 and May 2019 was conducted. RESULTS: Twenty-nine patients (mean age 46 years, M/F: 12/17) with 57 ophthalmic exams were identified. The most common ocular symptoms included irritation/pain (n = 28, 97%), redness (n = 24, 83%), pruritus (n = 18, 62%), discharge (n = 18, 62%), and light sensitivity (n = 6, 21%). The most frequent signs included conjunctival injection (n = 18, 62%), superficial punctate keratitis (n = 16, 55%), and papillary reaction (n = 8, 28%). Topical corticosteroids (TCS) (n = 23, 79%), tacrolimus (n = 6, 21%), and artificial tears (n = 7, 24%) were the most commonly used therapies. Of those with follow-up documentation (n = 21), 20 were noted to have partial or complete response with TCS based on symptoms and reduction of signs. Using our proposed symptom-based grading scale, scaled 1 to 5 based on the presence of common symptoms listed above, 66% (n = 19) requiring topical immunomodulating therapy were found in the 'severe' group (≥3 symptoms) and 17% (n = 5) were found in the 'mild' group (≤2 symptoms). CONCLUSIONS: This study provides insight into the commonly presenting ocular signs and symptoms associated with DAOSD and highlights the efficacy of TCS and other immunomodulators in improving symptoms associated with DAOSD. Based on our findings, we propose a symptom-based grading system that can guide nonophthalmic physicians regarding ophthalmology consult.

Keratouveitis caused by Euphorbia milii sap: case report and overview / Ceratouveíte causada pela seiva de Euphorbia millii: relato de caso e visão geral

ABSTRACT Objective: To report a case of anterior uveitis caused by Euphorbia milii sap and review all reported cases of keratouveitis related to this species. Methods: A 64-year-old male patient presented with a 10-day history of reduced visual acuity, pain, and photophobia in the left eye after an accidental contact with Euphorbia milii sap. Best-corrected visual acuity was initially 20/200. Upon examination, ciliary injection, mild corneal edema; fine keratic precipitates, and significant anterior chamber reaction. There was no vitritis, and fundoscopy was unremarkable. The patient initiated on topical steroid and tropicamide. Results: Best-corrected visual acuity in left eye improved to 20/20 after using eyedrops for 3 weeks, associated with complete resolution of anterior uveitis. Over the following 6 months, best-corrected visual acuity remained stable, and no evidence of recurrent inflammation was observed. Conclusion: To the best of our knowledge, this is the third reported case of keratouveitis caused by Euphorbia milii sap. As observed in other cases of keratouveitis caused by sap of this species, the clinical course is benign and characterized by moderate reaction of the anterior chamber, and corneal involvement of variable intensity.

RESUMO O objetivo foi relatar um caso de uveíte anterior induzida pela seiva da Euphorbia milii e revisar todos os casos relatados de ceratouveíte causados por essa espécie. Paciente do sexo masculino, 64 anos, apresentou história de 10 dias de evolução com redução da acuidade visual, dor e fotofobia no olho esquerdo, após contato acidental com a seiva da planta Euphorbia milii. A acuidade visual com melhor correção era inicialmente 20/200. O exame revelou injeção ciliar, edema de córnea leve, precipitados ceráticos finos e reação de câmara anterior significativa. Não havia vitreíte, e a fundoscopia não exibia alterações. Foram iniciados colírios de esteroides e tropicamida. A acuidade visual no olho esquerdo melhorou para 20/20 em 3 semanas com a utilização dos colírios, além de se ter alcançado a resolução completa da uveíte anterior. Nos 6 meses seguintes, a acuidade visual permaneceu estável, e não foi observada evidência de recorrência da inflamação. Até então, este é o terceiro caso relatado de ceratouveíte pela seiva da Euphorbia milii. Como visto nos demais casos de ceratouveíte induzidos pela seiva dessa espécie, o curso clínico é benigno e caracterizado por reação moderada da câmara anterior, com envolvimento corneano de intensidade variável.

Real-world experience of dupilumab treatment for atopic dermatitis in adults: a retrospective analysis of patients' records.

BACKGROUND: Clinical trial data for dupilumab, a monoclonal antibody against the interleukin-4 receptor (IL-4Rα), have shown that it is safe and effective for the treatment of moderate to severe atopic dermatitis in patients whose disease is resistant to other therapies. However, little real-world experience with dupilumab use has been reported thus far. The aim of this retrospective study was to assess overall outcomes in adult patients with atopic dermatitis (AD) treated with dupilumab. METHODS: A retrospective review of electronic medical records was conducted for patients treated with dupilumab in the Department of Dermatology at the University of California, Irvine. RESULTS: We analyzed the medical records of 77 AD patients who received dupilumab according to standard dosing and had at least one documented follow-up visit. In 66 patients (86%), dupilumab improved clinical disease severity, with 23 patients (30%) experiencing complete clearance on dupilumab. Dupilumab was generally well-tolerated and caused no serious adverse events. The most common side effects included dry eyes, conjunctivitis, and keratitis. The most common reason for discontinuation of treatment was lack of substantial clinical improvement or progression of disease severity, followed by ophthalmologic side effects. CONCLUSIONS: Overall, dupilumab was well-tolerated and resulted in clinical improvement in our patient population. These results provide additional important information on the safety and utility of dupilumab treatment for moderate to severe atopic dermatitis in the real-world clinical setting.

Ocular chemical burns from accidental exposure to topical dermatological medicinal agent.

We report a case of accidental ocular chemical injury by self-medication with a single application of a topical ayurvedic medication containing salicylic acid, phenol, and tincture iodine, which is being used in developing countries for treatment of various dermatological conditions.

Topical ayurvedic ointment-induced chemical injury presenting as bilateral acute keratitis.

A 40-years-old female patient was referred to the cornea clinic as a probable case of bilateral keratitis. The patient had a history of headache followed by acute onset of redness, pain and discharge from both eyes for 15 days. The patient was diagnosed as bilateral keratitis by the first contact physician and was started on topical antibiotics, cycloplegics and lubricating eye-drops. At presentation, both eyes had visual acuity of perception of light, conjunctival congestion, limbal blanching, diffuse corneal oedema and epithelial defect. A detailed history revealed application of Vicks VapoRub [topical ayurvedic analgesic which contains (per 100 g of product) menthol (2.82 g), camphor (5.25 g) and eucalyptol (1.49 mL) and excipients include thymol (0.1 g), turpentine oil (5.57 mL), nutmeg oil (0.54 mL), cedar wood oil and petrolatum)] on the forehead and eyelids for headache several times over 2-3 days before the onset. The patient further confirmed the accidental application of the ointment in the eyes. A provisional diagnosis of acute chemical injury with Vicks VapoRub was made and treatment with topical antibiotic, cycloplegic, steroid, lubricant and vitamin C was started. On follow-up, both eyes showed gradual resolution of corneal oedema and epithelial defect. Visual acuity improved in the left eye to 6/60 with no change in right eye due to corneal haze.

Comparison of 3 different anesthetic approaches for intravitreal injections: a prospective randomized trial.

PURPOSE: To compare the anesthetic effectiveness of topical proparacaine drops, subconjunctival lidocaine, and 2% lidocaine gel. METHODS: Ninety-two patients undergoing intravitreal injections were randomized to 1 of 3 groups: proparacaine 0.5% drops (Group Drops), proparacaine 0.5% drops plus subconjunctival lidocaine (Group SC), or 2% lidocaine gel (Group Gel). Patients were asked to score their pain experience using a visual analog scale of 0 to 10 immediately following the injections and 10 min, 1 h, 6 h, and 24 h after the injections. Patients also graded the overall injection experience as Excellent, Very Good, Fair, Poor, or Awful. The physician evaluated the patients' eye movement during intravitreal injection on 3 levels: (0) none or minimal, (1) not compromising the injection, and (2) compromising the injection. RESULTS: The patients in Group Drops had the worst mean pain scores during the injection and 10 min after, with the highest occurrence of movements compromising the procedure (Grade 2; 38.7%). The patients in Group SC had a higher percentage of good experiences (37.9%) but a higher incidence of chemosis (16.7%). The patients in Group Gel had similar overall pain scores to Group Drops patients but a higher incidence of keratitis (19.4%). There was no statistically significant correlation between the use of aspirin or anticoagulants and the occurrence of hyperemia or hyposphagma. CONCLUSION: Subconjunctival lidocaine was most effective in preventing pain and eye movements during intravitreal injections. Although 2% lidocaine gel produced a good overall experience for the patients, the incidence of keratitis was very high (19.4%). Therefore, we do not recommend 2% lidocaine gel as the first anesthetic choice for intravitreal injections. There is no evidence to suspend the use of aspirin or other anticoagulants drugs prior to intravitreal injections.

Comparison of 3 different anesthetic approaches for intravitreal injections: a prospective randomized trial / Comparação de três abordagens anestésicas diferentes para injeções intravítreas: um estudo prospectivo e randomizado

Purpose: To compare the anesthetic effectiveness of topical proparacaine drops, subconjunctival lidocaine, and 2% lidocaine gel. Methods: Ninety-two patients undergoing intravitreal injections were randomized to 1 of 3 groups: proparacaine 0.5% drops (Group Drops), proparacaine 0.5% drops plus subconjunctival lidocaine (Group SC), or 2% lidocaine gel (Group Gel). Patients were asked to score their pain experience using a visual analog scale of 0 to 10 immediately following the injections and 10 min, 1 h, 6 h, and 24 h after the injections. Patients also graded the overall injection experience as Excellent, Very Good, Fair, Poor, or Awful. The physician evaluated the patients’ eye movement during intravitreal injection on 3 levels: (0) none or minimal, (1) not compromising the injection, and (2) compromising the injection. Results: The patients in Group Drops had the worst mean pain scores during the injection and 10 min after, with the highest occurrence of movements compromising the procedure (Grade 2; 38.7%). The patients in Group SC had a higher percentage of good experiences (37.9%) but a higher incidence of chemosis (16.7%). The patients in Group Gel had similar overall pain scores to Group Drops patients but a higher incidence of keratitis (19.4%). There was no statistically significant correlation between the use of aspirin or anticoagulants and the occurrence of hyperemia or hyposphagma. Conclusion: Subconjunctival lidocaine was most effective in preventing pain and eye movements during intravitreal injections. Although 2% lidocaine gel produced a good overall experience for the patients, the incidence of keratitis was very high (19.4%). Therefore, we do not recommend 2% lidocaine gel as the first anesthetic choice for intravitreal injections. There is no evidence to suspend the use of aspirin or other anticoagulants drugs prior to intravitreal injections. .

Objetivo: Comparar a eficácia anestésica entre proparacaína tópica, lidocaína subconjuntival e lidocaína gel a 2%. Métodos: Noventa e dois pacientes em tratamento com injeções intravítreas foram randomizados para um de três grupos: proparacaína 0,5% gotas (Grupo gotas), proparacaína 0,5% gotas seguida de lidocaína subconjuntival (Grupo SC), ou lidocaína gel a 2%. (Grupo Gel). Os pacientes foram orientados a graduar a sua experiência de dor por uma escala visual analógica, numa escala de 0 a 10, imediatamente após as injeções, bem como 10 minutos, 1 hora, 6 horas e 24 horas após. Os pacientes também classificaram a experiência global de injeção como excelente, muito boa, regular, ruim ou horrível. O médico avaliou o movimento do olho do paciente durante a injeção intravítrea em três níveis: nenhuma ou mínima (0), não comprometendo a injeção (1), comprometendo a injeção (2). Resultados: Os pacientes do grupo gotas apresentaram uma graduação média de dor pior durante a injeção e 10 minutos após, com maior ocorrência de movimentos comprometendo a injeção (grau 2) (38,7%). Os pacientes do grupo SC, apresentaram maior percentual de boa experiência durante o procedimento (37,9%) e maior ocorrência de quemose (16,7%). Os pacientes do grupo Gel apresentaram escore de dor geral semelhante ao grupo Gotas e maior incidência de ceratite (19,4%). Não houve correlação estatisticamente significativa com o uso de aspirina ou anticoagulantes e a ocorrência de hiperemia ou hiposfagma. Conclusão: Lidocaína subconjuntival foi mais eficaz na prevenção da dor durante injeção intravítrea com movimentação ocular mínima. Embora os pacientes do grupo lidocaína gel a 2% tenham apresentado uma boa experiência, consideramos a incidência ceratite muito elevada (19,4%) e não recomendamos lidocaína gel a 2% como a primeira escolha como anestésico para injeções intravítreas. Não há evidência para a suspensão do uso de aspirina ou drogas anti-coagulantes em pacientes ...

[Pediatric exposures to laundry pods or capsules: more toxic than traditional laundry products?]. / Expositions des enfants aux lessives capsules, écodoses ou pods : plus toxiques que les lessives traditionnelles ?

UNLABELLED: New concentrated laundry pods, available on the European market for approximately 10 years, are associated with more severe intoxications compared to classic laundry detergents. AIM: To compare symptoms and severity after exposure to classic laundry detergents and new laundry pods in a pediatric population. MATERIAL AND METHODS: Retrospective study conducted between 1st January 2002 and 30th June 2013 including all laundry detergent exposure patients admitted to our tertiary level pediatric emergency unit. Collected data were age, sex, date, time and location of exposure, type of product (powder, liquid, tablets, pods), estimated ingested quantity, time of admission, clinical symptoms, severity, complications, and progression. RESULTS: Descriptive analysis: eighty-nine children were included. The mean age was 2.1 ± 1.5 years (range, 36 days to 10 years), 65% of patients were aged less than 2 years. The male:female ratio was 1.5 (males, 60%). After exposure, 57% of children were symptomatic and most frequently developed digestive symptoms (75%). Comparative analysis: compared to classic laundry detergent, children exposed to laundry pods were more symptomatic (96% versus 51%, P<0.0001), had more digestive signs (P=0.003), more frequently had bronchospasm (P=0.02), had a higher risk of ocular lesions (P=0.04), and exposure was more severe (poisoning severity score grade 2, 92% versus 59%, P<0.0001). COMMENTS: Laundry pod toxicity is more severe. The chemical composition of laundry pods has a higher concentration of surfactants and ethoxylated alcohols; they have a higher viscosity and hydrotropic power. The addition of water seems to modify the alkalinity, which explains the severity of ENT, gastric, and corneal lesions. CONCLUSION: The declaration to national poison centers of these intoxications should be pursued by emergency pediatricians, physicians, and pediatric intensivists. Family physicians can encourage parents to declare adverse effects to the National Consumer Product Safety Commission. Parents need to be better informed of the risk of laundry pods and strictly keep this type of product out of the reach of children. Given that it took 7 years after the first warning by the French poison centers to obtain safety recommendations for manufacturers, it is important to maintain pressure on companies to obtain the necessary modification of the physicochemical properties and child-resistant packaging.

Keratouveitis caused by Euphorbia trigona sap.

We present a case of a 40-year-old female with severe keratouveitis secondary to Euphorbia trigona plant sap. The patient dropped sap into both eyes to relieve itching and developed Euphorbia keratouveitis. Visual acuity was finger counting at 1 m in both eyes on presentation. On examination, eyelid edema, ciliary injection, corneal edema with Descemet membrane folds and exudate in the anterior chamber were seen bilaterally. With supportive treatment all signs and symptoms were relieved. Exposure to Euphorbia sap should be treated immediately to prevent sequelae like corneal scarring.

The use of topical honey in the treatment of corneal abrasions and endotoxin-induced keratitis in an animal model.

PURPOSE: To investigate the effect of topically applied honey on intact corneas, surgically induced corneal abrasions and endotoxin induced keratitis. MATERIALS AND METHODS: The effect of honey on the cornea was investigated by application of honey on intact corneas, wounded corneas and endotoxin-induced keratitis in Lewis rats. The corneas were wounded by creating an epithelial defect using a surgical blade, and the keratitis was induced by topically applying Pseudomonas aeruginosa endotoxin to scarified corneas. After treatment rats were sacrificed and cornea harvested in each case. Corneas were processed for paraffin embedding for histological and immuno-fluorescence staining. Corneas were also harvested and processed for total ribonucleic acid (RNA) isolation for reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for various growth factors and inflammatory chemokines/cytokines). RESULTS: Histological analysis revealed that no inflammation or morphological changes occurred after honey treatment in naive intact corneas. Vascular endothelial growth factor (VEGF) levels were also not altered after honey treatment. Topical application of honey to injured corneas resulted in faster epithelial healing and decreased expression of VEGF, transforming growth factor beta (TGF-ß), interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor necrosis factor alpha (TNF-α) in injured corneas. Our results also established that honey treatment reduced the inflammation in endotoxin-induced keratitis by reducing the levels of angiogenic factors (VEGF and TGF-ß), inflammatory cytokines (IL-12) and chemokines (CC chemokine receptor 5(CCR-5)). CONCLUSION: Short term use of honey on intact corneas can be safe. Honey has anti-angiogenic and anti-inflammatory properties that can be explored in several corneal inflammatory and infectious conditions.

Euphorbia lactea sap keratouveitis: case report and review of the literature.

PURPOSE: To describe a case of Euphorbia lactea sap keratouveitis and to review all reported cases of ocular toxicity caused by Euphorbia species. METHODS: Case report and review of literature. RESULTS: A 79-year-old woman presented 34 hours after she felt some sap of an E. lactea plant spray into her right eye. Visual acuity was counting fingers at 1 m. Examination revealed ciliary injection, 90% corneal epithelial defect, marked stromal edema with Descemet folds, and anterior-chamber flare with a 1-mm hypopyon. There was no vitreitis, and funduscopy was unremarkable. No foreign body was seen on B scan ultrasound or computed tomography scan of the orbits. Corneal scraping excluded bacterial and herpetic keratitis. Intensive topical antibiotic therapy was started with cephalothin 5% and gentamicin 0.9%, and the pupil was dilated with atropine. Topical steroids were started once the epithelial defect had healed. Examination 11 weeks after the injury revealed minimal subepithelial corneal haze and marked improvement in visual acuity. CONCLUSIONS: To the best of our knowledge, this is only the third reported case of E. lactea sap keratouveitis. The clinical course of E. lactea sap keratouveitis is compared with that reported for other Euphorbia species.

Late onset diffuse lamellar keratitis as a result of the toxic effect of Ecballium elaterium herb.

PURPOSE: To report a case of late onset diffuse lamellar keratitis (DLK) 11 months after LASIK due to Ecballium elaterium exposure. METHODS: A 25-year-old man underwent bilateral LASIK. No complications were observed during the early postoperative period. RESULTS: Eleven months after LASIK surgery, grade II DLK was diagnosed after an Ecballium elaterium herb seed burst and splashed into the patient's left eye. Topical steroid treatment was administered and DLK healed in 2 weeks without complication. CONCLUSIONS: Although DLK typically develops in the early postoperative period, it could occur months after surgery. Treatment should begin as soon as DLK is diagnosed.

[Pepper spray injuries of the anterior segment of the eye]. / Pfeffersprayverletzungen des vorderen Augensegmentes.

BACKGROUND: A wide variety of pepper sprays is currently available and gaining increasing popularity among both professional guardians and amateurs. Adverse side effects to the anterior segment of the eye are known but underestimated. HISTORY AND SIGNS: We present two cases with severe corneal and conjunctival damage after accidental self injury by a pepper spray (Jet Protector Guardian Angel), benzyl alcohol 90.1 %, capsaicinoids 2.6 %). THERAPY AND OUTCOME: Despite immediate and intensive irrigation, a complete epithelial defect, extensive ischemia to the limbus and the conjunctiva and a circular conjunctival chemosis were diagnosed. After slow re-epithelialization in both cases, a neurotrophic superficial keratitis, a reduced corneal sensibility and in one case deep stromal scarring were noted. CONCLUSIONS: Pepper spray application to the eye might result in severe and permanent damage to the corneo-conjunctival tissue which is not adequately addressed in the current literature. From the present case reports arise the discussion whether the irritative and lipophilic capsacin/benzyl alcohol mixture or the pyrotechnical additives nitrocellulose und sinoxide are responsible for the anterior segment injuries.

Calotropis procera (ushaar) keratitis.

PURPOSE: To report a case of permanent endothelial cell injury after intracorneal penetration of milky latex from Calotropis procera (ushaar). DESIGN: Interventional case report. METHODS: A 40-year-old patient developed painless corneal edema despite minimal epithelial injury after exposure to ushaar latex. RESULTS: Confocal and specular microscopy confirmed permanent endothelial cell loss with morphologic alteration after intracorneal penetration of ushaar latex. Corneal edema resolved completely after 2 weeks, although reduced endothelial cell count and abnormal morphology persisted. CONCLUSION: Ushaar latex is capable of penetrating the corneal stroma and inducing permanent loss of endothelial cells. Corneal edema resolves if sufficient endothelial cell viability is still present after resolution of ushaar keratitis.

Evaluation of preoperative and postoperative prophylactic regimens for prevention and treatment of diffuse lamellar keratitis.

PURPOSE: To investigate preoperative and postoperative prophylactic treatment with different pharmacological agents before flap cutting and exposure to a diffuse lamellar keratitis (DLK) causative agent. SETTING: Magill Research Center for Vision Correction, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: The study comprised 48 eyes of 24 Dutch-belted rabbits. Three days before a corneal flap was cut and the corneal interface was exposed to Pseudomonas aeruginosa lipopolysaccharide endotoxin, a DLK causative agent, the eyes were randomly assigned to treatment with a mast-cell stabilizer, a nonsteroidal antiinflammatory drug (NSAID), or a corticosteroid or left without treatment as controls. The treatment was maintained throughout the 1-week follow-up. Slitlamp examinations and photographs were performed at 1, 3, 5, and 7 days; DLK was graded by a masked observer from 0 (no DLK) to IV. Corneal interface scrapings were performed in selected eyes on day 7. RESULTS: At the end of the follow-up, 36 eyes were available for evaluation. At 1 week, 100% of the control eyes and the eyes treated with the mast-cell stabilizer developed DLK; in the NSAID-treated and corticosteroid-treated eyes, the DLK rate was 86% and 70%, respectively. At 1 day, the severity of DLK was significantly lower in eyes treated with the mast-cell stabilizer (0.44) and at 7 days, it was significantly lower in corticosteroid-treated eyes (0.3) than in the control group (1.5 and 1.4, respectively) (P<.05, Wilcoxon test). Corneal interface scraping from an eye with grade III DLK showed numerous inflammatory cells. CONCLUSIONS: Preoperative and postoperative treatment with corticosteroids significantly reduced the severity of DLK compared to the untreated control eyes in this animal model. Treatment with a mast-cell stabilizer and an NSAID had less effect on the postoperative course of DLK.

Efficacy of indomethacin 0.1% and fluorometholone 0.1% on conjunctival inflammation following chronic application of antiglaucomatous drugs.

BACKGROUND: Subclinical conjunctival inflammation has been shown to have a deleterious effect on the outcome of filtering surgery. The study was designed to assess the efficacy and safety of a non-steroidal anti-inflammatory ophthalmic solution (preservative-free indomethacin 0.1%) on conjunctival inflammation following chronic application of antiglaucomatous drugs, in comparison with a steroidal ophthalmic solution (preserved fluorometholone). METHODS: Eighty-nine glaucomatous patients were included in a randomised, multicentre study comparing two parallel groups of treatment given on the basis of 1 drop 4 times daily for 1 month before filtering surgery. Patients had been treated with one or more antiglaucomatous drugs for at least 3 years. The routine antiglaucomatous treatment was continued during the study. Evaluations were carried out at baseline and after 30 days of treatment. Conjunctival inflammation was assessed under masked conditions by means of conjunctival impression analysis which determined the percentage of cells expressing HLA-DR. The ocular surface was also examined using the fluorescein test and lissamine green staining. RESULTS: Paired conjunctival impression specimens available both on day 0 (D0) and day 30 (D30) involved 49 patients. Among them, 34 eyes had a positive expression of HLA-DR at inclusion. On D30, in patients positive to HLA-DR on D0, the percentage of cells expressing HLA-DR had significantly decreased in both treatment groups: the mean reduction was 29.7% from a baseline value of 51.4% in the indomethacin group ( P=0.019) and 32.5% from a baseline value of 48.7% in the fluorometholone group ( P<0.001). There was no significant difference between groups. Seven cases of drug-related superficial punctate keratitis were observed on D30 by means of a fluorescein test: one in the indomethacin group and six in the fluorometholone group. CONCLUSION: Both anti-inflammatory eyedrops were effective in reducing subclinical conjunctival inflammation before filtering surgery. Regarding superficial punctate keratitis, the corneal tolerance of preservative-free indomethacin 0.1% eyedrops seemed to be better than that of preserved fluorometholone eyedrops.