Treatment of corticosteroid-resistant Graves' orbitopathy with tocilizumab: a single-centre prospective study.

PURPOSE: To assess tocilizumab (TCZ) as an emergent treatment for corticosteroid-resistant active Graves' orbitopathy (GO). METHODS: We conducted a single-centre prospective study. We assessed TCZ in patients with active corticosteroid-resistant GO. Each patient received intravenous TCZ every four weeks until symptom stabilization. Our primary outcome was GO activity evaluated by the clinical activity score (CAS). The secondary outcomes included variation in thyroid-stimulating immunoglobulin (TSI). RESULTS: We included ten patients. Three patients had compressive neuropathy with visual field impairment and vision loss. CAS improved significantly in 100% of the patients included in the analysis, with a decrease in the mean CAS of 4.5 ± 1.2 points (p = .003). There was a significant decrease in the TSI after therapy, from 21.7 ± 22.9 at baseline to 4.0 ± 3.3 (p = .006). A mean of three infusions was necessary to drastically decrease the TSI amount. The baseline mean before TCZ was 4.7 ± 1.2 and the final mean after TCZ IV infusion was 0.2 ± 0.4. CONCLUSIONS: Our study showed the efficiency of TCZ in patients with GO resistant to corticosteroid therapy, as shown in previous studies. Our present work adds two important pieces of information: TCZ might be particularly useful for GO with compressive neuropathy and it is efficient regardless of initial TSI level. Considering the numerous advantages over steroids (high response rate and lower rate of adverse events), further randomized controlled trials should be conducted to assess the possible place of TCZ as a first-line treatment.

Using Optical Quality Analysis System for predicting surgical parameters in age-related cataract patients.

The Optical Quality Analysis System (OQAS, Visiometrics) provides objective measurements of image formed onto retina, by combining quantification of ocular media transparency and of optical aberrations. In order to evaluate its contribution in the assessment of age-related cataract, we conducted a monocentric clinical study to determine the relationships between clinical grading of lens opacity, OQAS parameters, and parameters required for cataract surgery by phacoemulsification with ultrasound (called "phacodynamics"). Clinical parameters were: best-corrected visual acuity (BCVA, expressed as Log of minimal angle resolution (logMAR)) and the lens opacity classification system III (LOCS III) as a gold standard determined by two independent observers who graded total cataract and nuclear, cortical and posterior sub capsular components. The OQAS provided an objective scatter index (OSI), a modulation transfer function (MTF, expressed in cycle per degree (cpd)) and a Strehl ratio (SR) used as an aberration marker. Patients were operated on by the same surgeon using a phacoemulsification machine that provided the cumulative dissipated energy (CDE) and total ultrasound time (US time) necessary to extract the lens. Patients with poor compliance, corneal or retinal diseases impairing OSI, or who required surgical settings variation, were excluded. Twenty-one eyes of 21 patients aged 76±8 years were analyzed. They were 11 pure nuclear, 3 pure cortical, and 7 mixed cataracts. Mean LOCS III and OSI were respectively: 4.86 ±2.03 and 6.12 ±3.07 (mean±SD). Medians (10°-90° percentiles) were: for BCVA 0.30 (0.10-0.70) logMAR, for MTF cutoff 9.31 (1.54-30.57) cpd, for SR 0.071 (0.042-0.146), for CDE 8.04 (5.74-23.29) and for US time 58 (39-116) seconds. LOCS III was significantly correlated (spearman r, rs) with BCVA (rs = 0.561, p = 0.008), CDE (rs = 0.457, p = 0.038) and US time (rs = 0.647, p = 0.002). The three OQAS parameters significantly correlated (all rs ≥ 0.526, p<0.05) with BCVA, and LOCS III grading, but the strongest correlations were found with OSI for cortical components and with MTF for nuclear components: only OSI may be used objectively to assess the effect of cortical components on optical quality, and MTF cutoff-integrating scattering and aberrations-seems the best objective parameter for clinical assessment of nuclear cataracts. The three OQAS parameters were also significantly correlated (rs) with CDE, and with US time only for pure nuclear cataracts: OSI had the strongest correlations with phacodynamics (rs = 0.693, p = 0.022 with CDE and rs = 0.703, p = 0.019 US time). OSI increased with cortical components not requiring higher CDE. When measured in optimal conditions (good compliance, no retinal or ocular surface or tear film diseases), the three OQAS parameters are complementary for objective grading of cataract. In the future, they may help to optimize surgical parameters, especially energy distribution, in femtosecond laser assisted cataract surgery.

In vivo and ex vivo confocal microscopy for the evaluation of surgical margins of melanoma.

We report the first series of melanomas (MMs) where the surgical margins were evaluated both by ex vivo confocal microscopy (EVCM) and in vivo reflectance confocal microscopy (RCM). We evaluated the surgical margins of 42 cutaneous MMs of lentigo maligna/lentigo maligna melanoma type and 2 mucosal MMs with EVCM. Cutaneous MMs also underwent RCM mapping. Imaging results were compared with histopathology. The rate of correct identification of the tumor margins (invaded or not invaded) was 97.6% for RCM (evaluations of cutaneous MMs) and 95.5% for EVCM (evaluations of both cutaneous and mucosal MMs). Our study showed that the MM extension is visible under EVCM and that the combination of in vivo RCM and EVCM can be a new strategy for the evaluation of surgical margins of MMs.

Dermoscopy for the Diagnosis of Conjunctival Lesions.

This article describes the present literature on dermoscopy of conjunctiva and shows the results of a dermoscopy study of 147 conjunctival tumors. Melanomas were characterized by a heavy pigmentation, irregular dots, and a higher prevalence of gray color compared with nevi. Squamous cell carcinomas had peculiar hairpin and glomerular vessels. Primary acquired melanoses were characterized by regularly distributed light brown dots. A large part of nevi had small cysts.

Handheld In Vivo Reflectance Confocal Microscopy for the Diagnosis of Eyelid Margin and Conjunctival Tumors.

Importance: The clinical diagnosis of conjunctival and eyelid margin tumors is challenging, and new noninvasive imaging techniques could be valuable in this field. Objective: To assess the diagnostic accuracy of handheld in vivo reflectance confocal microscopy (IVCM) for the diagnosis of eyelid margin and conjunctival tumors. Design: A prospective observational study was conducted at University Hospital of Saint-Etienne from January 2, 2011, to December 31, 2016 (inclusion of patients until December 31, 2015, and follow-up until December 31, 2016). A total of 278 consecutive patients with eyelid margin or conjunctival lesions were included. Conjunctival lesions were diagnosed with a conventional clinical examination using a slitlamp and by handheld IVCM. Final diagnoses were established by histopathologic examination for 155 neoformations suspicious for being malignant through clinical and/or IVCM examination that were excised and on follow-up of 12 months or longer for the remaining 140 lesions. Main Outcomes and Measures: Sensitivity, specificity, and positive and negative predictive values for malignant tumors of the conjunctiva and eyelid margin were calculated using clinical examination with slitlamp and handheld IVCM. Results: In the 278 patients (136 [48.9%] females; mean [SD] age, 59 [21] years), a total of 166 eyelid margin and 129 conjunctival lesions were included in the analysis. Of the 155 excised neoformations with a histopathologic diagnosis, IVCM showed higher sensitivity compared with clinical examination conducted with the slitlamp for malignant tumors of the eyelid margin (98% vs 92%) and conjunctiva (100% vs 88%). The specificity for malignant eyelid margin tumors was higher for IVCM than for slitlamp examination (74% vs 46%), but slightly less for malignant conjunctival tumors (78% vs 88%). Analysis of all neoformations (155 excised and 140 in follow-up) confirmed these differences in the diagnostic accuracy of the clinical examination and IVCM. The presence of hyperreflective Langerhans cells mimicking malignant melanocytes was the main cause for misdiagnosis of malignant conjunctival tumors with IVCM. Conclusions and Relevance: Handheld IVCM could be a useful tool for the identification of malignant conjunctival tumors. Further studies are required to confirm the usefulness of this device and identify possible features that can differentiate Langerhans cells from malignant melanocytes to prevent the misdiagnosis of melanoma using IVCM.

'En face' ex vivo reflectance confocal microscopy to help the surgery of basal cell carcinoma of the eyelid.

BACKGROUND: Ex vivo confocal microscopy is a recent imaging technique for the perioperative control of skin tumour margins. Up to date, it has been used in the fluorescence mode and with vertical sections of the specimen margins. The aim of this study was to evaluate its use in the reflectance mode and with a horizontal ('en face') scanning of the surgical specimen in a series of basal cell carcinoma of the eyelid. DESIGN: Prospective consecutive cohort study was performed at the University Hospital of Saint-Etienne, France. PARTICIPANTS: Forty-one patients with 42 basal cell carcinoma of the eyelid participated in this study. METHODS: Basal cell carcinomas were excised with a 2-mm-wide clinically safe margin. The surgical specimens were analysed under ex vivo confocal microscopy in the reflectance mode and with an en face scanning in order to control at a microscopic level if the margins were free from tumour invasion. Histopathogical examination was later performed in order to compare the results. MAIN OUTCOME MEASURES: Sensitivity and specificity of ex vivo confocal microscopy for the presence of tumour-free margins. RESULTS: Ex vivo confocal microscopy results were consistent with histopathology in all cases (tumour-free margins in 40 out of 42 samples; sensitivity and specificity of 100%). CONCLUSIONS: Ex vivo confocal microscopy in the reflectance mode with an 'en face' scanning can control tumour margins of eyelid basal cell carcinomas and optimize their surgical management. This procedure has the advantage on the fluorescent mode of not needing any contrast agent to examine the samples.

In vivo confocal microscopy of pine processionary caterpillar hair-induced keratitis.

PURPOSE: Multimodal imaging of processionary caterpillar hair-induced keratitis with anterior segment optical coherence tomography and in vivo confocal microscopy. METHODS: Case report. RESULTS: A 25-year-old woman presented with acute keratitis induced by multiple tiny processionary caterpillar hairs. She initially experienced severe pain and moderate vision loss, which gradually improved within a few weeks. Diagnosis was confirmed by in vivo confocal microscopy showing a pathognomonic image strictly comparable with ex vivo microscopy photography. CONCLUSIONS: To the best of our knowledge, this is the first case of corneal in vivo confocal imaging of a caterpillar hair with confirmation by ex vivo microscopy.

Handheld reflectance confocal microscopy for the diagnosis of conjunctival tumors.

PURPOSE: To evaluate whether the handheld in vivo reflectance confocal microscopy that has been recently developed for the study of skin tumors is suitable for the diagnosis of conjunctival tumors. DESIGN: Prospective study, observational case series. METHODS: We prospectively evaluated the reflectance confocal microscopy features of 53 conjunctival lesions clinically suspicious for tumors of 46 patients referred to the University Hospital of Saint-Etienne (France) by using the handheld device. Twenty-three lesions were excised (3 nevi, 10 melanomas, 5 squamous cell carcinoma, 2 lymphomas, and 3 pinguecula/pterygium) while the other 30, presenting no reflectance confocal microscopy malignant features, were under follow-up for at least 1 year. Clinical reflectance confocal microscopy and histologic diagnosis were compared. RESULTS: In vivo reflectance confocal microscopy diagnosis was in agreement with the histologic diagnosis in all cases and none of the lesions that were not excised show any clinical progression under follow-up. CONCLUSION: In vivo reflectance confocal microscopy with a handheld dermatology-dedicated microscope can play a role in the noninvasive diagnosis of conjunctival lesions. Further studies should be performed to better define the diagnostic ability of this technique.

The role of in vivo confocal microscopy in the diagnosis of eyelid margin tumors: 47 cases.

BACKGROUND: Handheld in vivo reflectance confocal microscopy (IVCM) is a new imaging method that allows noninvasive diagnosis of cutaneous tumors but to date it has not been used in the study of eyelid tumors. OBJECTIVE: We sought to evaluate the suitability of IVCM for eyelid margin tumors. METHODS: We prospectively evaluated the IVCM features of 47 eyelid margin lesions, clinically suspicious of malignancy; 35 of these were excised whereas the other 12, with no IVCM malignant features, were followed up for at least 1 year. Clinical, IVCM, and histologic diagnoses were compared. RESULTS: IVCM showed sensitivity and specificity of 100% and 69.2%, respectively, for malignancy (basal cell carcinoma, squamous cell carcinoma, and melanoma). The follow-up of the 12 nonexcised lesions did not show any clinical progression. LIMITATIONS: The lesions showing neither clinical nor IVCM features for malignancies were not biopsied in view of the potential functional and aesthetic consequences of eyelid margin surgery. CONCLUSION: Used with a handheld dermatology-specific microscope, IVCM can play a role in the noninvasive diagnosis of eyelid margin lesions. Further studies are needed to better define diagnostic criteria of eyelid tumors and improve the specificity of this technique.

[Surgical treatment of blepharospasm: results of a study of 138 patients using an improved disability scale]. / Traitement chirurgical du blépharospasme: evaluation des résultats par une echelle d'invalidité clinique sur une etude de 138 patients.

We applied a new blepharospasm clinical disability scale to the evaluation of blepharospasm surgery in a group of 138 patients. This scale analyzes six parameters of daily life, namely reading, watching television, household tasks, walking, employment, and driving. The patients had either essential blepharospasm or pretarsal dystonia. Frontalis suspension of the eyelid gave slightly better functional results than orbicularis resection in some patient subgroups.

Assessment of blepharospasm surgery using an improved disability scale: study of 138 patients.

PURPOSE: To assess a new scale for grading functional disability in a series of patients operated on for blepharospasm resistant to treatment by botulinum toxin (BT) injections. METHODS: The bicentric study included 138 patients: 80 (58%) with essential blepharospasm; 46 (33%) with apraxia of eyelid opening; and 12 (9%) with intermediate forms. They had undergone orbicularis myectomy (92 cases, 67%), frontalis suspension (31 cases, 22%), or both (15 cases, 11%). Functional disability was assessed by using an original scale covering 6 daily life activities, each graded using 5 levels from 0 (no disability) to 4 (activity impossible). The score obtained was related to the total of activities actually performed to produce a functional disability score (FDS) from 0 to 100. Each patient's FDS was prospectively determined, before surgery and 3 months after surgery (M3). In patients who, after surgery, required a further course of BT injections, the FDS was assessed immediately before the third injection. RESULTS: The mean FDS fell significantly, from 78 +/- 15 (standard deviation) before surgery to 45 +/- 21 at M3 (p < 0.01%), whatever the clinical form of essential blepharospasm or surgical procedure. The mean postoperative FDS was significantly lower in the 62 patients (45%) weaned off BT than in the unweaned group, respectively (31 +/- 17 versus 56 +/- 18; p < 0.01). In the latter group, the mean FDS after BT reinjection (34 +/- 19) fell to a level comparable with that of the weaned patients. CONCLUSIONS: This accurate, easy-to-use scale makes it possible to quantify in patients with blepharospasm functional improvement as the result of surgery and, where applicable, of BT reinjection.