Frequencies and predictors of subcutaneous and intraosseous injection with four epinephrine autoinjector devices.

BACKGROUND: To prevent anaphylaxis-associated illness, intramuscular-epinephrine injection is recommended. Subcutaneous injection may reduce efficacy and intraosseous injection promotes morbidity. A few studies suggest that commercially-available thigh-epinephrine autoinjectors (EAIs) may induce subcutaneous/intraosseous injection in some adults. OBJECTIVE: This cross-sectional study estimated the subcutaneous/intraosseous-injection rates of four EAIs by comparing their needle lengths to the ultrasound-measured skin-to-muscle-depth (STMD) and skin-to-bone-depth (STBD) of the mid-thigh of allergic adults. Patient factors that predict subcutaneous-EAI injection were also determined. METHODS: Thigh-ultrasound was conducted in a convenience-recruited cohort with minimal and maximal compression to estimate the effect of EAI-induced compression. Subcutaneous/intraosseous-injection rates were estimated for Anapen, EpiPen, Jext, and Emerade. Multivariate analyses for subcutaneous-injection risk were conducted with age, sex, abdominal and thigh circumferences, and upper-arm skinfold thickness. RESULTS: 68 patients were recruited. Compression respectively thinned the subcutaneous tissue and muscle by 1 and 9 mm on average. Projected subcutaneous-injection rates with/without compression were high for Anapen (65-66%), moderate for EpiPen and Jext (29-38%), and lowest for Emerade (13-21%). Compression introduced a small intraosseous-injection risk with Emerade (4%). Female sex predicted subcutaneous injection (Odds-ratios 1.3-2.0, all p<0.001). Depending on the EAI, 29-97% of women and 0-41% of men would be injected subcutaneously. Older men were at risk of intraosseous Emerade injection. Obesity-related variables predicted subcutaneous injection poorly. CONCLUSION: Anapen associated with high subcutaneous-injection rates. EpiPen and Jext were projected to provide intramuscular injection in all men without risk of intraosseous injection. Emerade yielded the lowest subcutaneous-injection rates in women. Compression largely affected the muscle.

Narrative review after post-hoc trial analysis of factors that predict corneal endothelial cell loss after phacoemulsification: Tips for improving cataract surgery research.

PURPOSE: Identifying pre/perioperative factors that predict corneal endothelial-cell loss (ECL) after phacoemulsification may reveal ways to reduce ECL. Our literature analysis showed that 37 studies have investigated one or several such factors but all have significant limitations. Therefore, the data of a large randomized controlled trial (PERCEPOLIS) were subjected to post-hoc multivariate analysis determining the ability of nine pre/perioperative variables to predict ECL. METHODS: PERCEPOLIS was conducted in 2015-2016 to compare two phacoemulsification techniques (subluxation and divide-and-conquer) in terms of 3-month ECL. Non-inferiority between the techniques was found. In the present study, post-hoc univariate and multivariate analyses were conducted to determine associations between ECL and age, sex, cataract density, preoperative endothelial-cell density, phacoemulsification technique, effective phaco time (EPT), and 2-hour central-corneal thickness. The data are presented in the context of a narrative review of the literature. RESULTS: Three-month data were available for 275 patients (94% of the randomized cohort; mean age, 74 years; 58% women). Mean LOCSIII cataract grade was 3.2. Mean EPT was 6 seconds. Mean ECL was 13%. Only an older age (beta = 0.2%, p = 0.049) and higher EPT (beta = 1.2%, p = 0.0002) predicted 3-month ECL. Cataract density was significant on univariate (p = 0.04) but not multivariate analysis. The other variables did not associate with ECL. CONCLUSIONS: Older age may amplify ECL due to increased endothelial cell fragility. EPT may promote ECL via cataract density-dependent and -independent mechanisms that should be considered in future phacoemulsification research aiming to reduce ECL. Our literature analysis showed that the average ECL for relatively unselected consecutively-sampled cohorts is 12%.

Five-year clinical outcomes of 107 consecutive DMEK surgeries.

PURPOSE: The long-term clinical outcomes, postoperative complications, and graft survival of Descemet-membrane endothelial keratoplasty (DMEK) remain poorly understood. We retrospectively assessed these variables in all consecutive eyes that underwent DMEK for any indication in 2014-2018. The findings were compared to the long-term DMEK studies of five other groups (3-10-year follow-up). METHODS: Patients underwent ophthalmological tests preoperatively, at 1, 3, 6, and 12 postoperative months, and then annually. Five-year graft survival was determined by Kaplan-Meier estimator. Change in best-corrected visual acuity (BCVA), endothelial-cell density (ECD), and central-corneal thickness (CCT) at each timepoint was determined. RESULTS: 107 eyes (80 patients; 72 years old; 67% female) underwent first-time DMEK for uncomplicated Fuchs endothelial corneal dystrophy (94% of eyes), pseudophakic bullous keratopathy (3%), and regraft after previous keratoplasty (3%). The most common complication was graft detachment requiring rebubbling (18%). Thirteen grafts (12%) failed at ≤15 months. Cumulative 5-year graft-survival probability was 88% (95% confidence intervals = 79-94%). BCVA improved from 0.6 logMAR preoperatively to 0.05 logMAR at 1 year (p<0.0001) and then remained stable. Donor ECD dropped by 47% at 6 postoperative months and then continued to decrease by 4.0%/year. Five-year endothelial-cell loss was 65% (from 2550 to 900 cells/mm2). CCT dropped from 618 to 551 µm at 5 years (p<0.0001). These findings are generally consistent with previous long-term DMEK studies. CONCLUSIONS: DMEK has low complication and high graft-survival rates and excellent clinical outcomes that persist up to 5 years post-surgery. DMEK seems to be a safe and effective treatment in the long term.

Postoperative, but not preoperative, central corneal thickness correlates with the postoperative visual outcomes of Descemet membrane endothelial keratoplasty.

Descemet membrane endothelial keratoplasty (DMEK) restores visual acuity in patients with progressive corneal endothelial diseases such as Fuchs endothelial corneal dystrophy (FECD). However, patients often prefer to delay the surgery as long as possible, even though outcomes are poorer in advanced FECD. A recent study proposed that preoperative central corneal thickness (CCT) of ≥625 µm associated with worse best spectacle-corrected visual acuity (BSCVA) after DMEK for FECD. Since this threshold could signal to both surgeons and patients when to perform DMEK, we further explored the relationship between CCT and BSCVA with a retrospective cohort study. The cohort consisted of all patients with FECD who underwent DMEK in a tertiary-care hospital in 2015-2020 and were followed for 12 months. Extremely decompensated corneas were not included. Relationships between preoperative CCT and BSCVA on days 8 and 15 and months 1, 3, 6, and 12 were examined with Pearson correlation analyses. Eyes with preoperative CCT <625 or ≥625 µm were also compared in terms of postoperative BSCVA. Relationships between postoperative CCT and final BSCVA were also explored. The cohort consisted of 124 first-operated eyes. Preoperative CCT did not correlate with postoperative BSCVA at any timepoint. Eye subgroups did not differ in postoperative BSCVA. However, postoperative CCT at 1-12 months correlated significantly with 12-month BSCVA (r = 0.29-0.49, p = 0.020-0.001). Thus, postoperative, but not preoperative, CCT correlated with postoperative BSCVA. This phenomenon may reflect factors that distort preoperative CCT measurements but disappear after surgery. This observation and our analysis of the literature suggest that while there is a relationship between CCT and post-DMEK visual acuity, preoperative CCT measurements may not always adequately reflect that relationship and may therefore not be a reliable predictor of DMEK visual outcomes.

Biomechanics of keratoconus: Two numerical studies.

BACKGROUND: The steep cornea in keratoconus can greatly impair eyesight. The etiology of keratoconus remains unclear but early injury that weakens the corneal stromal architecture has been implicated. To explore keratoconus mechanics, we conducted two numerical simulation studies. METHODS: A finite-element model describing the five corneal layers and the heterogeneous mechanical behaviors of the ground substance and lamellar collagen-fiber architecture in the anterior and posterior stroma was developed using the Holzapfel-Gasser-Ogden constitutive model. The geometry was from a healthy subject. Its stroma was divided into anterior, middle, and posterior layers to assess the effect of changing regional mechanical parameters on corneal displacement and maximum principal stress under intraocular pressure. Specifically, the effect of softening an inferocentral corneal button, the collagen-based tissues throughout the whole cornea, or specific stromal layers in the button was examined. The effect of simply disorganizing the orthogonally-oriented posterior stromal fibers in the button was also assessed. The healthy cornea was also subjected to eye rubbing-like loading to identify the corneal layer(s) that experienced the most tensional stress. RESULTS: Conical deformation and corneal thinning emerged when the corneal button or the mid-posterior stroma of the button underwent gradual softening or when the collagen fibers in the mid-posterior stroma of the button were dispersed. Softening the anterior layers of the button or the whole cornea did not evoke conical deformation. Button softening greatly increased and disrupted the stress on Bowman's membrane while mid-posterior stromal softening increased stress in the anterior layers. Eye rubbing profoundly stressed the deep posterior stroma while other layers were negligibly affected. DISCUSSION: These observations suggest that keratoconus could be initiated, at least partly, by mechanical instability/damage in the mid-posterior stroma that then imposes stress on the anterior layers. This may explain why subclinical keratoconus is marked by posterior but not anterior elevation on videokeratoscopy.

Membranoproliferative glomerulonephritis after intravitreal vascular growth factor inhibitor injections: A case report and review of the literature.

Systemic administration of agents that inhibit vascular endothelial growth factor (VEGF) and therefore vascular proliferation is often used to treat various cancers. However, these agents are associated with a number of side effects, including proteinuria and renal injury. Intravitreal injection of anti-VEGF agents has become the cornerstone of macular disease treatment. Since these agents cross the blood-retina barrier and enter the circulation, systemic side effects have been reported. We report the novel case of a 57-year-old patient who presented with macular oedema secondary to central retinal vein occlusion, underwent three monthly loading-dose injections with the anti-VEGF agent ranibizumab, and 2 weeks after the second injection presented with biopsy-verified membranoproliferative glomerulonephritis. Twelve weeks after presenting with renal failure and 10 weeks after his last anti-VEGF injection, the patient demonstrated spontaneous recovery of his kidney function. The patient had a history that promoted renal fragility, including hypertension, liver transplantation 6 years earlier for alcohol-related cirrhosis and new-onset diabetes mellitus after transplant. Our literature review and case suggest that although adverse renal events after intravitreal anti-VEGF injections are very rare, ophthalmologists and nephrologists should be aware of this risk.

Ability of routinely collected clinical factors to predict good visual results after primary Descemet membrane endothelial keratoplasty: a cohort study.

BACKGROUND: A comprehensive analysis of routinely collected pre/perioperative demographic/clinical factors that could predict final visual acuity after primary Descemet membrane endothelial keratoplasty (DMEK) has not been conducted previously. METHODS: A retrospective monocenter cohort study was performed with consecutive patients with Fuchs endothelial corneal dystrophy (FECD) who underwent DMEK or triple-DMEK (DMEK combined with cataract surgery) in 2016-2020 in a French tertiary-care hospital. DMEK-only patients were pseudophakic. Patients were followed for 12 months. Surgery was considered successful when 12-month best-corrected visual acuity (BCVA) was ≤0.1 logMAR (≥0.8). Exploratory multivariate analysis was conducted with the following routinely collected variables to determine their ability to predict 12-month BCVA: patient age and sex; graft donor age; triple DMEK; preoperative values of BCVA, endothelial cell density (ECD), central corneal thickness (CCT), and mean anterior keratometry; and rebubbling. RESULTS: Of 100 eyes (100 patients; mean age, 72 years; 61% female), 81 achieved a 12-month BCVA of ≤0.1 logMAR. Logistic regression analysis showed that older age was a significant prognosticator for 12-month BCVA > 0.1 logMAR (Odds Ratio = 0.914, 95% confidence intervals = 0.846-0.987; p = 0.02). CONCLUSIONS: An older age associated with worse visual acuity outcomes after DMEK. This was confirmed by our analysis of the literature and supports the notion that DMEK should be conducted without delay once symptoms appear. Patient sex, donor age, triple-DMEK, and anterior keratometry also did not predict final BCVA in the literature. Preoperative CCT, ECD, and BCVA, and rebubbling occasionally appear in the literature as BCVA predictors, possibly reflecting an underlying ECD-BCVA axis.

Evolution of corneal transplantation techniques and their indications in a French corneal transplant unit in 2000-2020.

PURPOSE: This retrospective cohort study assessed the evolution of corneal transplantation and its indications in the last 21 years (2000-2020) in a specialized ophthalmology department in a tertiary referral center in France. METHODS: The surgical techniques and indications, patient age and sex, and postoperative best-corrected visual acuity (BCVA) 6 months after keratoplasty were extracted. RESULTS: In total, 1042 eyes underwent keratoplasty in 2000-2020. Annual numbers of corneal transplantations increased by 2.2-fold. Penetrating keratoplasty (PKP) was the sole technique for the first 11 years. Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) were introduced in 2011 and 2014, respectively. Cases of both quickly increased, accounting for 28% and 41% of cases in 2015-2020, respectively. Eventually, DSAEK and DMEK were respectively used for most pseudophakic bullous keratopathy (PBK) and all Fuchs endothelial cell dystrophy (FECD) cases. PKP cases declined to 27%. Deep anterior lamellar keratoplasty (DALK) was rare (3% of all cases). These changes associated with rises in PBK and particularly FECD cases, and a strong decline in keratoconus, causing FECD, PBK, and keratoconus to move from being the 4th, 1st, and 3rd most common indications to the 1st, 2nd, and 6th, respectively. On average, BCVA improved by 0.1-0.3 logMAR. Patient age dropped steadily over time. Female predominance was observed. CONCLUSIONS: The invention of DSAEK and then DMEK precipitated an enormous change in clinical practice and a large expansion of keratoplasty to new indications. This study confirms and extends previous findings in other countries.

Identification of the preoperative and perioperative factors that predict postoperative endothelial cell density after Descemet membrane endothelial keratoplasty: A retrospective cohort study.

Low postoperative endothelial-cell density (ECD) plays a key role in graft failure after Descemet-membrane endothelial keratoplasty (DMEK). Identifying pre/perioperative factors that predict postoperative ECD could help improve DMEK outcomes. This retrospective study was conducted with consecutive adult patients with Fuchs-endothelial corneal dystrophy who underwent DMEK in 2015-2019 and were followed for 12 months. Patients underwent concomitant cataract surgery (triple-DMEK) or had previously undergone cataract surgery (pseudophakic-DMEK). Multivariate analyses assessed whether: patient age/sex; graft-donor age; preoperative ECD, mean keratometry, or visual acuity; triple DMEK; surgery duration; surgical difficulties; and need for rebubbling predicted 6- or 12-month ECD in the whole cohort or in subgroups with high/low ECD at 6 or 12 months. The subgroups were generated with the clinically relevant threshold of 1000 cells/mm2. Surgeries were defined as difficult if any part was not standard. In total, 103 eyes (95 patients; average age, 71 years; 62% women) were included. Eighteen eyes involved difficult surgery (14 difficult graft preparation or unfolding cases and four others). Regardless of how the study group was defined, the only pre/perioperative variable that associated significantly with 6- and 12-month ECD was difficult surgery (p = 0.01, 0.02, 0.05, and 0.0009). Difficult surgery also associated with longer surgery duration (p = 0.002). Difficult-surgery subgroup analysis showed that difficult graft dissection associated with lower postoperative ECD (p = 0.03). This association may reflect endothelial cell loss due to excessive graft handling and/or an intrinsic unhealthiness of the endothelial cells in the graft that conferred unwanted physical properties onto the graft that complicated its preparation/unfolding.

Graft Thickness at 6 Months Postoperatively Predicts Long-Term Visual Acuity Outcomes of Descemet Stripping Automated Endothelial Keratoplasty for Fuchs Dystrophy and Moderate Phakic Bullous Keratopathy: A Cohort Study.

PURPOSE: It remains unclear whether preoperative central graft thickness (CGT) contributes to visual outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK). This retrospective cohort study examined the ability of preoperative and postoperative CGT to predict 12-month best spectacle-corrected visual acuity (BSCVA) after DSAEK for Fuchs endothelial corneal dystrophy/moderate pseudophakic bullous keratopathy/second graft. METHODS: All consecutive patients who underwent DSAEK in 2015 to 2018 were included. The primary end point was 12-month BSCVA. DSAEK-CGT was measured preoperatively and 6 times between postoperative day 8 and month 12. Eyes were divided according to preoperative CGT 130 µm (ultrathin-DSAEK threshold) or 6-month postoperative CGT 100 µm (mean 6-month postoperative DSAEK-CGT). The t test assessed CGT evolution of the 4 groups over time. Multivariate analyses examined whether preoperative CGT or 6-month CGT categories predicted 12-month BSCVA. Multivariate analysis assessed the preoperative/perioperative factors that predicted 6-month CGT. RESULTS: A total of 108 eyes (68 patients) underwent DSAEK. Preoperative CGT was >130 and ≤130 µm in 87 and 21 eyes, respectively. Postoperative CGT was >100 and ≤100 µm in 50 and 58 eyes, respectively. Thin 6-month postoperative grafts thinned significantly more relative to preoperative thickness than thick grafts ( P < 0.001). Preoperative CGT subgroups did not show this difference. Six-month postoperative CGT ( P = 0.01), but not preoperative CGT, predicted 12-month BSCVA. Preoperative CGT strongly predicted 6-month CGT ( P = 0.0003). CONCLUSIONS: Postoperative, but not preoperative, DSAEK-CGT predicted 6-month BSCVA. The correlation between preoperative and postoperative CGT and interstudy variation in preoperative CGT measurement accuracy may explain literature disparities regarding the importance of preoperative CGT in DSAEK outcomes.

Corneal Endothelial Cell Loss After Endocapsular and Supracapsular Phacoemulsification: The PERCEPOLIS Randomized Clinical Trial.

PURPOSE: Subluxation techniques are superior to divide-and-conquer in procedure duration, pain, and ultrasound quantity, but their safety in endothelial cell loss (ECL) is unclear. This randomized single-blind noninferiority clinical trial aimed to determine whether subluxation supracapsular phacoemulsification techniques are inferior to a reference endocapsular technique (divide-and-conquer) regarding postoperative corneal ECL. METHODS: Patients (aged18 years or older) with greater than +0.2 logarithm of the minimum angle of resolution best spectacle-corrected visual acuity and normal to severe density cataract were randomized to subluxation or divide-and-conquer phacoemulsification in 2015 to 2016. Follow-up with ophthalmic tests was conducted on day 4 and months 1, 3, and 12. The primary study outcome was ECL at all time points. Secondary study end points were operative variables, including effective phaco time and procedure duration. A clinically relevant noninferiority ECL limit was established on the basis of the literature. RESULTS: In total, 292 patients (mean age, 73 yrs; 59% female) were randomized and underwent subluxation (n = 148) or divide-and-conquer (n = 144). Day 4 and month 1, 3, and 12 data were available for 243, 270, 275, and 198 patients, respectively. The unexpectedly high dropout at 12 months meant that the 12-month ECL data could only be assessed qualitatively. Surgery was successful in all patients. Subluxation was noninferior to divide-and-conquer in ECL. Effective phaco times were similar, but subluxation associated with shorter procedure duration. CONCLUSIONS: The subluxation technique was noninferior to divide-and-conquer regarding postoperative ECL, at least in the first 3 months, and associated with reduced intervention time. Subluxation techniques may be suitable alternatives to endocapsular techniques.Clinical Trial Registration-URL: ClinicalTrials.gov. Unique identifier: NCT02535819.

Efficacy and safety of single-step transepithelial photorefractive keratectomy with the all-surface laser ablation SCHWIND platform without mitomycin-C for high myopia: A retrospective study of 69 eyes.

BACKGROUND: Studies suggest that transepithelial photorefractive keratectomy (TransPRK) with the all-surface laser ablation (ASLA)-SCHWIND platform is effective and safe for both low-moderate myopia and high myopia. In most studies, mitomycin-C is administered immediately after surgery to prevent corneal opacification (haze), which is a significant complication of photorefractive keratectomy in general. However, there is evidence that adjuvant mitomycin-C induces endothelial cytotoxicity. Moreover, a recent study showed that omitting adjuvant mitomycin-C did not increase haze in low-moderate myopia. The present case-series study examined the efficacy, safety, and haze rates of eyes with high myopia that underwent ASLA-SCHWIND TransPRK without adjuvant mitomycin-C. METHODS: All consecutive eyes with high myopia (≤-6 D) that were treated in 2018-2020 with the SCHWIND Amaris 500E® TransPRK excimer laser without adjuvant mitomycin-C in a tertiary-care hospital (France) and were followed up for 6 months were identified. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), and spherical equivalent (SE) were recorded before and after surgery. Postoperative haze was graded using the 4-grade Fantes scale. Efficacy rate (frequency of eyes with 6-month UCVA ≤0.1 logMAR), safety rate (frequency of eyes that lost <2 BSCVA lines), predictability (frequency of eyes with 6-month SE equal to target SE±0.5 D), efficacy index (mean UCVA at 6 months/preoperative BSCVA), and safety index (BSCVA at 6 months/preoperative BSCVA) were computed. RESULTS: Sixty-nine eyes (38 patients) were included. Mean preoperative and 6-month SE were -7.44 and -0.05 D, respectively. Mean 6-month UCVA and BSCVA were 0.00 and -0.02 logMAR, respectively. Efficacy rate and index were 95.7% and 1.08, respectively. Safety rate and index were 95.7% and 1.13, respectively. Predictability was 85.5%. Grade 3-4 haze never arose. At 6 months, the haze rate was zero. CONCLUSIONS: ASLA-SCHWIND TransPRK without mitomycin-C appears to be safe as well as effective and accurate for high myopia.

Effect of patient-led cooperative follow-up by general practitioners and community pharmacists on osteoporosis treatment persistence.

AIM: Osteoporosis is a major risk factor for fractures. Poor persistence with osteoporosis medication hampers outcomes. This study assessed whether encouraging the formation of patient-led follow-up cooperatives between general practitioners (GPs) and community pharmacists improved medication persistence. METHODS: All consecutive patients who attended an osteoporosis patient education program were invited to participate. They were given a logbook containing questionnaires they would bring to 6-monthly visits to their GP and pharmacist. The effect of this 3-year cooperative follow-up on persistence with medication and lifestyle changes was assessed. RESULTS: In total, 121 patients (average age, 67 years; 93% female) participated. Poor cooperation between GPs and pharmacists was noted. Nevertheless, medication persistence ranged from 83% to 91% over the 6 visits. However, since patient drop-out rates were high and questionnaire return rates were low, a post-study medical chart review was performed. This confirmed that persistence was high (74%-83%) at 3 years post-enrollment, even for oral bisphosphonate-treated patients (73%-76%). However, adoption of anti-osteoporosis lifestyle changes was poor throughout the study: one- to two-thirds of the patients did not alter their diet, physical activity, or surroundings to prevent falls. CONCLUSION: One study goal, namely, to encourage GPs and pharmacists to cooperate in patient follow-up, was not achieved. However, high medication persistence was observed. This may reflect the education program, patient empowerment, personalized attention from study personnel, and being in a study. Patient-centered approaches can thus significantly increase medication persistence in osteoporosis. Ongoing education may be needed to improve patient adoption of and persistence with lifestyle changes.

Oral management in a patient with Gardner-Diamond Syndrome: A case report.

INTRODUCTION: Gardner-Diamond Syndrome (GDS) is rare. It is characterized by the spontaneous formation of painful erythematous skin lesions that develop into ecchymoses within 24 h and then disappear progressively over days to weeks. The complications can be serious. PRESENTATION OF CASE: A 35-year-old man with GDS was admitted to the oral surgery department for dental infectious focus eradication. Clinical and radiological examinations indicated extraction of tooth 17. It was performed with local anaesthesia, cardiac monitoring, and verbal reassurance therapy. After delivering anaesthesia, two intra-oral hematomas and a bruise quickly developed. Cardiovascular manifestations and a spontaneous painful right temporal erythematous skin lesion appeared in the next 24 h. The patient was briefly hospitalized in the cardiovascular medicine department. Over the next 21 days, some haematomas regressed, another expanded, and a new cervico-thoracic ecchymosis developed. DISCUSSION: The surgical and post-surgical complications in this clinical case raise several points concerning the oral management of patients with GDS. We propose to apply: verbal reassurance therapy during surgery; presurgical haematological evaluation and postsurgical daily haematological follow-up; and atraumatic surgery with intra- and post-surgical haemostatic precautions. Systematic antibiotic prophylaxis and non-steroidal anti-inflammatory drugs may also be useful. Other possibilities include desmopressin acetate, corticosteroids, antihistamines, plasmapheresis, and immunosuppressive agents; however, few cases have been treated with these strategies. CONCLUSION: This case highlights the difficult management of patients with GDS who require oral surgery. Further studies are needed to improve the oral surgical procedures in these patients and to establish a systematic management algorithm.

A structurally available encephalitogenic epitope of myelin oligodendrocyte glycoprotein specifically induces a diversified pathogenic autoimmune response.

Multiple sclerosis is an inflammatory disease of the CNS that involves immune reactivity against myelin oligodendrocyte glycoprotein (MOG), a type I transmembrane protein located at the outer surface of CNS myelin. The epitope MOG92-106 is a DR4-restricted Th cell epitope and a target for demyelinating autoantibodies. In this study, we show that the immune response elicited by immunization with this epitope is qualitatively different from immune responses induced by the well-defined epitopes myelin basic protein (MBP) 84-96 and proteolipid protein (PLP) 139-151. Mice with MOG92-106-, but not with MBP84-96- or PLP139-151-induced experimental autoimmune encephalomyelitis developed extensive B cell reactivity against secondary myelin Ags. These secondary Abs were directed against a set of encephalitogenic peptide Ags derived from MBP and PLP as well as a broad range of epitopes spanning the complete MBP sequence. The observed diversification of the B cell reactivity represents a simultaneous spread toward a broad range of antigenic epitopes and differs markedly from T cell epitope spreading that follows a sequential cascade. The Abs were of the isotypes IgG1 and IgG2b, indicating that endogenously recruited B cells receive help from activated T cells. In sharp contrast, B cell reactivity in MBP84-96- and PLP139-151-induced experimental autoimmune encephalomyelitis was directed against the disease-inducing Ag only. These data provide direct evidence that the nature of the endogenously acquired immune reactivity during organ-specific autoimmunity critically depends on the disease-inducing Ag. They further demonstrate that the epitope MOG92-106 has the specific capacity to induce a widespread autoimmune response.