Efficacy of human C1 esterase inhibitor concentrate for treatment of ACE-inhibitor induced angioedema.

BACKGROUND: ACE inhibitor (ACEi) induced angioedema predominantly affects the upper aerodigestive tract. As ACEi induced angioedema is mediated by bradykinin, therapeutic response to antihistamines and glucocorticoids remains unsatisfactory. In bradykinin mediated hereditary angioedema, C1-esterase inhibitor (C1INH) is an effective and approved treatment since many years. Our aim was to evaluate the therapeutic effect of C1INH in ACEi induced angioedema. METHODS: We performed a double-blind, parallel-group, multicentre randomised placebo-controlled trial between December 2013 and September 2018. Eligible were adults with ACEi induced angioedema with airway obstruction. Participants were randomised 1:1 to single doses of either C1INH (20 IU/kg) or placebo (0.9% NaCl) i.v in addition to standard care (i.v. 500 mg prednisolone and 2.68 mg clemastine) i.v. Composite symptom scores were assessed at baseline and up to 48 h, at discharge and 1 week after discharge. Physician assessed time to complete oedema resolution (TCER) and time to onset of relief (TOR). RESULTS: 30 patients (16 C1INH, 14 placebo) were randomised and dosed. 25 (9 C1INH, 12 placebo) completed the study. TCER was 29.63 h ± 15.56 h in the C1INH and 17.29 h ± 10.40 h in the placebo arm (p = 0.0457). TORs were 4.13 h ± 3.38 h and 2.86 h ± 1.29 h for C1INH and placebo, respectively (p = 0.4443). There were no adverse events related to study medication. CONCLUSIONS: In the context of baseline application of steroids and antihistamines C1INH was inferior in the treatment of ACEi induced angioedema when compared to placebo with respect to time to complete resolution of symptoms. Eudra-CT Number: 2012-001670-28.

INVESTIGATING MICROANGIOPATHY USING SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH SUSAC SYNDROME.

PURPOSE: To determine whether optical coherence tomography angiography is of diagnostic utility for Susac syndrome (SuS) by quantifying microvascular retinal changes. METHODS: We enrolled 18 eyes of 9 healthy controls and 18 eyes of 9 patients with chronic SuS (12 had previous branch retinal artery occlusions and 6 were clinically unaffected). Images of the fovea were taken using an optical coherence tomography angiography system. Analysis included vessel density, fractal dimension, vessel diameter, and measurements of the foveal avascular zone (area, eccentricity, acircularity index, and axis ratio) in deep and superficial retinal layers. RESULTS: Skeleton density and inner ring vessel density were significantly lower in patients with SuS (skeleton density: Susac 0.11 ± 0.01 vs. controls 0.12 ± 0.01, P = 0.027. VD: SuS 0.39 ± 0.04 vs. controls 0.42 ± 0.02, P = 0.041). Eccentricity and axis ratio were significantly higher in patients with SuS (EC: Susac 0.61 ± 0.11, controls 0.51 ± 0.10, P = 0.003; axis ratio: Susac 1.57 ± 0.28, controls 1.39 ± 0.11, P = 0.005). SuS eyes (affected and unaffected) had poorer outcomes of the remaining vascular parameters compared with controls (P > 0.05). CONCLUSION: Optical coherence tomography angiography identified chronic microvascular changes in the eyes of patients with chronic SuS. Even clinically unaffected SuS eyes showed poorer vascular parameters. Although further research is needed, this noninvasive imaging modality seems to have the potential to serve as a valuable additive diagnostic tool.

Etiology and predictors of cluster attacks of hereditary angioedema that recur despite pharmaceutical treatment.

Introduction: Hereditary angioedema (HAE) is a disease that leads to recurrent swelling of the skin and mucous membranes, including the upper airway tract. Apart from being deadly, these attacks can be debilitating, which leads to a poor quality of life in patients. Clinicians are occasionally confronted with patients who have recurrent attacks despite treatment with C1 esterase inhibitor concentrate or ß2-receptor antagonists. The goal of this study was to investigate repeated attacks that occur 48 hours to 7 days ("cluster attacks") after treatment, to determine why they occur and the factors that may be associated with them, and thus to prevent their occurrence. Methods: We conducted a multicenter mixed retrospective-prospective study with data acquired from all documented attacks in our patients with collective (n = 132) between 2015 and 2018. Results: Eighty-five percent (n = 132) of our total patient collective (N = 156) agreed to participate in the study. Nine percent of these patients (n = 12) had cluster attacks, with a total of 48 cluster attacks. The data procured from the patients were mixed retrospective-prospective. Approximately 72% of all the cluster attacks were caused by exogenous stimuli (41% due to psychological stress, 29% due to physical stimuli, and 2% due to menstruation). Cluster attacks occurred in 7% of the patients who received prophylactic therapy in comparison with 12.5% of patients who received on-demand therapy. Cluster attacks comprised 48.4% of all the attacks that patients with cluster-attacks (n= 9) experienced. In addition, the patients who were underdosing their C1 esterase inhibitor treatment had cluster attacks more often. A lower "time to repeated attack" was seen in the patients who received on-demand therapy compared with those who received prophylactic therapy. Discussion: The percentage of the patients who had attacks as a result of exogenous triggers was higher in the cluster-attack group (70.5%) compared with the general HAE population (30-42%). Repeated attacks, therefore, were strongly associated with external triggers. The patients who received prophylactic treatment and who experienced cluster attacks were highly likely to have been underdosing, which may explain the repeated attacks despite treatment. In the patients prone to cluster attacks, prophylaxis should be considered.

Surgical Technique to Retrieve a Migrated Lester Jones Lacrimal Tube.

PURPOSE: To describe a technique for retrieving an inferomedially migrated Jones lacrimal tube. METHODS: The distal end of the migrated Jones tube is visualized directly via the nose. The tip of an endoilluminator (23 Gauge Constellation Vision Systems) is bent to form a 45° to 60° angle using a mosquito forceps and inserted into the distal opening of the tube. The endoilluminator is used to push the tube upward toward the original medial canthal opening and limit downward displacement as the caruncular area is surgically explored. The light transilluminating the tube facilitates its visualization and retrieval in the caruncular area. A new tube may be threaded through the same passage, or if the ostium is traumatized, through a new passage. RESULTS: This technique is time-efficient and has proven to be safe and successful in subsequent patients. CONCLUSIONS: The described technique aids in retrieving an inferomedially migrated Jones tube with minimal trauma to the surrounding structures.

Quantitative Optical Coherence Tomography Angiography in Patients with Moyamoya Vasculopathy: A Pilot Study.

Moyamoya (MM) disease is a chronic cerebrovascular disease that can lead to progressive stenosis of the terminal portions of the internal carotid arteries and their proximal branches. We sought to investigate and quantify retinal vascular changes in patients with MM vasculopathy (MMV) using optical coherence tomography angiography (OCTA) compared to healthy controls. Our findings reveal retinal microvascular changes in patients with MMV and highlights the potential of OCTA imaging for the detection of subclinical retinal pathology.

IMPACT OF LONG-TERM INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR ON PREEXISTING MICROSTRUCTURAL ALTERATIONS IN DIABETIC MACULAR EDEMA.

PURPOSE: Evaluation of the influence of long-term intravitreal anti-vascular endothelial growth factor treatment on preexisting retinal microstructural alterations in patients with diabetic macular edema. METHODS: Eyes with diabetic macular edema and a history of ≥ 20 intravitreal anti-vascular endothelial growth factor (aflibercept and/or ranibizumab) injections were included in this retrospective study. Primary outcome was the extent of disorganization of retinal inner layers, alterations at the outer plexiform layer/Henle fiber layer junction, disruption of external limiting membrane/ellipsoid zone, disruption of retinal pigment epithelium/Bruch complex, and retinal atrophy at baseline versus after ≥ 20 intravitreal injections as visualized by spectral-domain optical coherence tomography images. RESULTS: Of 383 eyes screened, 37 eyes were included in the current study. With the exception of outer plexiform layer/Henle fiber layer junction restoration, no significant changes regarding microstructural alterations between baseline and end of study were encountered after long-term anti-vascular endothelial growth factor (disorganization of retinal inner layers P = 0.381, outer plexiform layer/Henle fiber layer junction P = 0.001, external limiting membrane/ellipsoid zone P = 0.524, retinal pigment epithelium/Bruch complex P = 0.122, retinal atrophy P = 0.317). Best-corrected visual acuity significantly increased over the course of the study, corresponding to central retinal thickness and intraretinal fluid reduction (all P < 0.0001). The extent of microstructural alterations was negatively correlated with best-corrected visual acuity (P < 0.05). CONCLUSION: Apart from outer plexiform layer/Henle fiber layer junction layer restoration, no effect on preexisting retinal alterations was encountered after long-term intravitreal injections. Thus, intravitreal ranibizumab or aflibercept did not have a major effect (neither positive nor negative) on microstructural alterations.

LOW ENDOPHTHALMITIS RATES AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS IN AN OPERATION ROOM: A Retrospective Multicenter Study.

PURPOSE: To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in three European hospitals performed in an operation room (OR) under sterile conditions. METHODS: A retrospective multicenter study between 2003 and 2016 at three European sites, City Hospital Triemli Zurich, Switzerland (CHT), Zealand University Hospital Roskilde, Denmark (ZUH) and University Clinic Bern, Switzerland (UCB). Intravitreal injection (IVI) database of each department was reviewed. All anti-vascular endothelial growth factor injections were performed using a standardized sterile technique in an operation room. Injection protocols were similar between the three sites. No preinjection antibiotics were given. Postoperative antibiotics varied among sites. RESULTS: A total of 134,701 intravitreal injections were performed at the 3 sites between 2003 and 2016. Ten cases of presumed endophthalmitis were documented: 4 in 50,721 at CHT (95% CI: 0.0071-0.0087%), 2 in 44,666 at ZUH (95% CI: 0.0039-0.0051%), and 4 in 39,314 at UCB (95% CI: 0.0092-0.011%). This results in one case in 13,470 intravitreal injections and a combined incidence of 0.0074% per injection (95% CI: 0.0070-0.0078%). Positive cultures were found in 4 out of 10 presumed endophthalmitis cases. CONCLUSION: The standardized sterile technique in an operation room with laminar airflow showed very low rates of endophthalmitis at three European sites.

Angio-OCT de la zona avascular foveal en ojos con oclusión venosa de la retina.

Objetivo: El objetivo del estudio comprendía visualizar y cuantificar las alteraciones patológicas de la zona avascular foveal (ZAF) mediante angio-OCT en ojos con oclusión venosa de la retina (OVR) en comparación con el ojo contralateral sano. Procedimientos: La angio-OCT se llevó a cabo mediante el sistema Avanti® RTVue 100 XR (Optovue Inc., Fremont, Calif., EE. UU.). Los bordes de la capa vascular superficial (CVS) se definieron como 3 µm por debajo de la membrana limitante interna y 15 µm por debajo de la capa plexiforme interna y, para la capa vascular profunda (CVP), como 15 y 70 µm por debajo de la membrana limitante interna y de la capa plexiforme interna, respectivamente. La longitud de la ZAF horizontal, vertical y máxima de la CVS y la CVP en cada ojo se midió de forma manual. Además, se midió el ángulo entre el diámetro máximo de la ZAF y el plano papilomacular. Resultados: La angio-OCT representó los defectos dentro de la vasculatura en el área perifoveal en ojos con oclusión de rama venosa de la retina (ORVR; n = 11) y con oclusión de la vena central de la retina (OVCR; n = 8). Esto resultó en un crecimiento del diámetro máximo de la ZAF en ojos con OVR (n = 19) en comparación con el ojo contralateral (n = 19; 921 ± 213 frente a 724 ± 145 µm; p = 0,008). Además, se observó una correlación significativa entre la mejor agudeza visual corregida (MAVC) y el diámetro máximo de la ZAF en la CVP (ρ de Spearman = -0,423, p < 0,01). Por último, en los ojos con OVR, el ángulo entre el plano papilomacular y el diámetro máximo de la ZAF se dio tan solo en el 21,05% (CVS) y en el 15,79% (CVP) de los casos a 0 ± 15 ó 90 ± 15°, respectivamente. En ojos sanos, estos ángulos (que supuestamente representan una configuración de la ZAF regular) fueron más prevalentes (CVS 68,42 frente a 21,05%, p = 0,003; CVP 73,68 frente a 15,79%, p < 0,001). Conclusiones: La angio-OCT muestra alteraciones morfológicas de la ZAF en ojos con OVCR y ORVR. La correlación del diámetro máximo de la ZAF con la MAVC indica que estas alteraciones resultan funcionalmente relevantes.

Optical coherence tomography angiography of the foveal avascular zone in diabetic retinopathy.

PURPOSE: To analyze foveal avascular zone (FAZ) dimensions and symmetry in patients with diabetic retinopathy (DR) compared to healthy controls using optical coherence tomography angiography (OCT angiography). METHODS: OCT angiography was performed via an Avanti® RTVue 100 XR OCT system (Optovue, Inc., Fremont, CA, USA) in patients with diabetes mellitus (DM) and healthy adults. A frame centered on the fovea was used for FAZ measurements. The borders of the superficial vascular layer were defined as 3 µm below the internal limiting membrane (ILM) and 15 µm below the inner plexiform layer (IPL), and for the deep vascular layer as15 µm and 70 µm below the IPL, respectively. Angles of maximum FAZ diameter were measured in all eyes by two graders. RESULTS: In healthy eyes (N = 25), the FAZ surrounding vascular arcades were intact, showing a vertical or horizontal oval symmetrical formation with a maximum diameter usually on the horizontal or vertical axis. Diabetic eyes (N = 29) presented with disintegrity of the vascular arcades, resulting in an enlarged FAZ. In the superficial layer, the mean horizontal FAZ diameter was significantly larger in the DR group (753 µm ±272 µm) than in the control group (573 µm ±177 µm, p = 0.029). The difference was even more pronounced in the deep layer, with a mean value of 659 µm ±194 µm in the control group and 1009 µm ±342 µm in the DR group (p = 0.001). Furthermore, in the superficial layer, the angle of the maximum FAZ diameter was 0° (±15°) or 90° (±15°) in 72.0 % of healthy eyes. In eyes with DR, the angle was 0° (±15°) or 90° (±15°) in only 6.9 % of cases, due to the irregular configuration of the FAZ. CONCLUSIONS: OCT angiography is capable of imaging retinal vasculature without dye injection. Our data suggest that it can detect disintegrity of the vascular arcades surrounding the FAZ, thus differentiating DM from healthy eyes. Vascular abnormalities were more pronounced in the deep vascular layer.

Optical Coherence Tomography Angiography of the Foveal Avascular Zone in Retinal Vein Occlusion.

PURPOSE: The aim of the study was to visualize and to quantify pathological foveal avascular zone (FAZ) alterations through optical coherence tomography angiography (OCT-A) in eyes with retinal vein occlusion (RVO) in comparison to the unaffected fellow eyes. PROCEDURES: OCT-A was conducted with the Avanti® RTVue 100 XR system (Optovue Inc., Fremont, Calif., USA). The borders of the superficial vascular layer (SVL) were defined as 3 µm below the internal limiting membrane and 15 µm below the inner plexiform layer, and for the deep vascular layer (DVL) as 15 and 70 µm below the inner plexiform layer, respectively. The length of the horizontal, vertical and maximum FAZ was manually measured for the SVL and DVL in each eye. Additionally, the angle between the maximum FAZ diameter and the papillomacular plane was measured. RESULTS: OCT-A depicted defects within the perifoveal vasculature in eyes with branch retinal vein occlusion (BRVO; n = 11) and central retinal vein occlusion (CRVO; n = 8). These resulted in an enlargement of the maximum FAZ diameter in eyes with RVO (n = 19) in comparison to the healthy fellow eyes (n = 19; 921 ± 213 vs. 724 ± 145 µm; p = 0.008). Furthermore, a significant correlation was found between best-corrected visual acuity (BCVA) and the maximum FAZ diameter in the DVL (Spearman's x03C1; = -0.423, p < 0.01). Lastly, in the eyes with RVO, the angle between the papillomacular plane and the maximum FAZ diameter was only in 21.05% (SVL) and 15.79% (DVL) of the cases at 0 ± 15 or 90 ± 15°, respectively. In healthy eyes, these angles (which putatively represent a regular FAZ configuration) were more prevalent (SVL 68.42 vs. 21.05%, p = 0.003; DVL 73.68 vs. 15.79%, p < 0.001). CONCLUSION: OCT-A shows morphological alterations of the FAZ in eyes with CRVO and BRVO. The correlation of the maximum FAZ diameter with BCVA suggests that these alterations are functionally relevant.

Accuracy of Repetitive Ocular Vestibular-Evoked Myogenic Potentials to Diagnose Myasthenia Gravis in Patients With Ptosis or Diplopia.

BACKGROUND AND OBJECTIVES: We developed repetitive ocular vestibular-evoked myogenic potentials (roVEMP) as an electrophysiologic test that allows us to elicit the characteristic decrement of extraocular muscles in patients with ocular myasthenia gravis (OMG). Case-control studies demonstrated that roVEMP reliably differentiates patients with OMG from healthy controls. We now aimed to evaluate the diagnostic accuracy of roVEMP for OMG diagnosis in patients with ptosis and/or diplopia. METHODS: In this blinded prospective diagnostic accuracy trial, we compared roVEMP in 89 consecutive patients presenting with ptosis and/or diplopia suspicious of OMG with a multimodal diagnostic approach, including clinical examination, antibodies, edrophonium testing, repetitive nerve stimulation of accessory and facial nerves, and single-fiber EMG (SFEMG). We calculated the roVEMP decrement as the ratio between the mean of the first 2 responses compared with the mean of the sixth-ninth responses in the train and used cutoff of >9% (unilateral decrement) in a 30 Hz stimulation paradigm. RESULTS: Following a complete diagnostic work-up, 39 patients (44%) were diagnosed with ocular MG, while 50 patients (56%) had various other neuro-ophthalmologic conditions, but not MG (non-MG). roVEMP yielded 88.2% sensitivity, 30.2% specificity, 50% positive predictive value (PPV), and 76.5% negative predictive value (NPV). For comparison, SFEMG resulted in 75% sensitivity, 56% specificity, 55.1% PPV, and 75.7% NPV. All other diagnostic tests (except for the ice pack test) also yielded significantly higher positive results in patients with MG compared with non-MG. DISCUSSION: The study revealed a high sensitivity of 88.2% for roVEMP in OMG, but specificity and PPV were too low to allow for the OMG diagnosis as a single test. Thus, differentiating ocular MG from other neuro-ophthalmologic conditions remains challenging, and the highest diagnostic accuracy is still obtained by a multimodal approach. In this study, roVEMP can complement the diagnostic armamentarium for the diagnosis of MG. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with diplopia and ptosis, roVEMP alone does not accurately distinguish MG from non-MG disorders. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03049956.

Metastatic neuroendocrine tumor masquerading as orbital cysticercosis.

Orbital metastases secondary to neuroendocrine tumors are exceedingly rare. We present a unique case of a 30-year-old female initially presenting with fever, chills, periorbital swelling, and painful proptosis. CT orbits revealed two ovoid-shaped ring-enhancing lesions in the right lateral and superior rectus muscles and clear sinuses, atypical for infectious post-septal cellulitis. Further work-up included serologic analysis, auto-immune panel, and MRI. Further imaging showed pseudocystic orbital lesions mimicking orbital cysticercosis. Additionally, given the bilateral nature of the lesions and patient's country of origin, this parasitic process was highly suspected. A course of albendazole and steroids led to resolution of symptoms. With a presentation at age 30, this is by far the youngest case reported in literature to date.

Long-term outcomes of fornix reconstruction and cicatricial entropion repair in ocular mucous membrane pemphigoid and drug-related secondary pemphigoid.

OBJECTIVE: To investigate the long-term outcomes of fornix reconstruction and cicatricial entropion repair in patients with ocular mucous membrane pemphigoid (MMP) and secondary MMP. METHODS: Retrospective chart review of patients with MMP undergoing either fornix reconstruction (with amniotic membrane or buccal mucosal graft) or Wies cicatricial entropion repair between January 1, 2000, and September 1, 2020. Patients had a positive mucosal biopsy and (or) clinical features of MMP or secondary MMP. The primary outcome was overall success of fornix reconstruction based on fornix depth maintenance at latest follow-up. Secondary outcomes included resolution of trichiasis, visual acuity, and improvement of subjective symptoms. RESULTS: Eight patients (10 eyes) with a diagnosis of MMP (3 males and 5 females; median age, 71 years) and 4 patients (4 eyes) with a diagnosis of secondary MMP (2 females and 2 male; median age, 87 years) were enrolled. Mean follow-up was 22.7 months (range, 0.3-87.5 months) for MMP patients and 15.4 months (range, 3.0-43.9 months) for secondary MMP patients. For MMP eyes, 30.0% underwent fornix reconstruction, 60.0% underwent entropion repair, and 10.0% received both. Re-formation of symblepharon and loss of fornix depth occurred in all MMP eyes at an average of 6.4 ± 7.0 months postoperatively, and trichiasis recurred in all patients at the last follow-up visit. In secondary MMP patients, 75.0% of the eyes showed recurrence of symblepharon, and 66.7% re-formed trichiasis. Both MMP and secondary MMP patients had short-term symptom improvements. CONCLUSIONS: Fornix reconstruction and cicatricial entropion repair in our cohort of MMP and secondary MMP patients resulted in short-term symptomatic improvement, but recurrence was seen, on average, at 6 months postoperatively.

Liposomal Inhalation after Tracheostomy-A Randomized Controlled Trial.

BACKGROUND: Tracheostomy is a common procedure in critical care. The aim of this study was to evaluate the application of a liposomal inhalation compared to standard physiologic saline (SPS) inhalation on basis of objective and subjective parameters of airway inflammation. METHODS: We evaluated in this two-armed, double-blinded and randomized control group study the effect of liposomal compared with SPS inhalation in newly tracheotomized patients. The primary endpoint was defined as trend of tracheobronchial IL-6 secretion at day 1 compared to day 10. Further objective and subjective parameter were evaluated. RESULTS: Fifty patients were randomized in each arm. Tracheal IL-6 levels decreased significantly only after liposomal inhalation. Both inhalative agents seem to have an effect on the respiratory impairment after tracheostomy. Subjective patient impairment was reduced significantly from day 1 to day 10 after tracheostomy with liposomal inhalation. CONCLUSIONS: Liposomal inhalation demonstrated an advantage over SPS inhalation in newly tracheotomized patients.

Topography-Guided Photorefractive Keratectomy for Postkeratoplasty Astigmatism: Long-Term Outcomes.

PURPOSE: To evaluate the long-term efficacy and safety of topography-guided photorefractive keratectomy (TG-PRK) for postkeratoplasty refractive error correction. METHODS: A retrospective interventional case series of 54 eyes of 50 patients who underwent previous corneal transplants. Unaided distance visual acuity (UDVA) and best corrected visual acuity (CDVA), manifest refraction, mean central keratometric value, mean keratometric astigmatism, and postoperative complications were reviewed. RESULTS: Final follow-up was at mean 31 (±17) months. Sixteen point seven percent of eyes underwent more than 1 surface ablation. Mean UDVA improved from 0.96 ± 0.06 logarithm of the minimum angle of resolution (LogMAR) preoperatively to 0.46 ± 0.05 LogMAR of resolution at the final follow-up (Bonferroni, P < 0.0001). Mean UDVA improved by 4.4 Snellen lines. Improvement in CDVA was not significant, although a significant improvement was noted when eyes with preoperative CDVA <20/40 were analyzed separately (t test, P = 0.005). Mean astigmatism improved from -4.4 ± 0.26 D preoperatively to -2.4 ± 0.26 D at the final follow-up (Bonferroni, P < 0.0001), whereas mean SEQ improved from -2.5 ± 0.39 D preoperatively to -1.1 ± 0.25 D (Bonferroni, P = 0.02). In total, 9% at the preoperative visit and 55% at the final visit had less than 2 D of astigmatism, respectively. Keratometric astigmatism decreased from 5.24 ± 0.36 D preoperatively to 2.98 ± 0.34 D at the final follow-up (t test, P < 0.0001). No eyes developed clinically significant haze, 14.8% developed regression, and 13% had a reduction of 2 or more CDVA lines. CONCLUSIONS: Postkeratoplasty topography-guided photorefractive keratectomy has good long-term efficacy and safety, resulting in significant UDVA, refractive, and keratometric improvement. Regression can occur after the first year of treatment, emphasizing the importance of long-term follow-up.

Diagnosing Myasthenia Gravis With Repetitive Ocular Vestibular Evoked Myogenic Potentials.

Timely and accurate diagnosis of myasthenia gravis, particularly in patients with fluctuating, isolated ocular involvement, remains challenging. Serological antibody testing and repetitive nerve stimulation of peripheral muscles usually have low sensitivity in these patients. Edrophonium testing may cause adverse events, single-fiber electromyography (SFEMG) is time-consuming and both tests are often unavailable outside specialized institutions. Repetitive ocular vestibular evoked myogenic potential (roVEMP) stimulation has recently been introduced to facilitate the diagnosis of myasthenia gravis. Similar to repetitive nerve stimulation, roVEMPs detect muscle decrements with the benefit of being non-invasive and allowing for direct measurement of the extraocular muscles. This review summarizes the clinical evidence of the diagnostic value of roVEMP for myasthenia. Prospective clinical trials have demonstrated high sensitivity and specificity. RoVEMPs are of particular interest in challenging myasthenia subgroups with isolated ocular involvement, negative serology, and/or negative conventional electrophysiological results. Optimal roVEMP repetition rates of 20-30 Hz have been identified. This promising novel diagnostic tool merits further attention and investigation to establish its value as a clinical test for myasthenia.

Repetitive ocular vestibular evoked myogenic potentials in myasthenia gravis.

OBJECTIVE: To validate the repetitive ocular vestibular evoked myogenic potentials (RoVEMP) test for diagnostic use in myasthenia gravis (MG) and to investigate its value in diagnostically challenging subgroups. METHODS: The RoVEMP test was performed in 92 patients with MG, 22 healthy controls, 33 patients with a neuromuscular disease other than MG (neuromuscular controls), 4 patients with Lambert-Eaton myasthenic syndrome, and 2 patients with congenital myasthenic syndrome. RESULTS: Mean decrement was significantly higher in patients with MG (28.4% ± 32.2) than in healthy controls (3.2% ± 13.9; p < 0.001) or neuromuscular controls (3.8% ± 26.9; p < 0.001). With neuromuscular controls as reference, a cutoff of ≥14.3% resulted in a sensitivity of 67% and a specificity of 82%. The sensitivity of the RoVEMP test was 80% in ocular MG and 63% in generalized MG. The RoVEMP test was positive in 6 of 7 patients with seronegative MG (SNMG) with isolated ocular weakness. Of 10 patients with SNMG with negative repetitive nerve stimulation (RNS) results, 73% had an abnormal RoVEMP test. The magnitude of decrement was correlated with the time since the last intake of pyridostigmine (B = 5.40; p = 0.019). CONCLUSIONS: The RoVEMP test is a new neurophysiologic test that, in contrast to RNS and single-fiber EMG, is able to measure neuromuscular transmission of extraocular muscles, which are the most affected muscles in MG. Especially in diagnostically challenging patients with negative antibody tests, negative RNS results, and isolated ocular muscle weakness, the RoVEMP test has a clear added value in supporting the diagnosis of MG. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that RoVEMP distinguishes MG from other neuromuscular diseases.

Repetitive ocular vestibular evoked myogenic potential stimulation for the diagnosis of myasthenia gravis: Optimization of stimulation parameters.

OBJECTIVE: To determine the most effective stimulation parameters for the diagnosis of ocular myasthenia gravis (MG) using repetitive ocular vestibular evoked myogenic potentials (oVEMP) for quantification of the extraocular muscle response decrement. METHODS: Repetitive bone-conducted oVEMPs were elicited in 18 MG patients and 20 healthy subjects. We compared four different stimulus repetition rates (20 Hz, 30 Hz, 40 Hz, 50 Hz) and 100 Hz continuous stimulation, as well as recordings from the inferior oblique muscles and the lateral rectus muscles to determine the most sensitive and specific oVEMP parameters for decrement detection. RESULTS: Repetitive stimulation at all tested repetition rates with recordings from inferior oblique muscles allowed for effective differentiation between MG patients and healthy subjects. Among all repetition rates, 30 Hz showed a trend towards superiority, with a sensitivity of 71% and a specificity of 94% (area under the curve (AUC) 0.88) when using the smaller decrement of the two eyes and -10% as cutoff. Considering the larger decrement for analysis (-9% as cutoff), sensitivity increased to 82%, but specificity decreased to 78% (AUC 0.81). CONCLUSIONS: Our study demonstrates, that repetitive oVEMP stimulation elicits a robust decrement in the inferior oblique muscles of MG patients at repetition rates between 20 Hz and 50 Hz, with a probable optimum at 30 Hz. SIGNIFICANCE: Repetitive inferior oblique oVEMP stimulation with optimal stimulus parameters facilitates early and accurate diagnosis of ocular MG.

Diagnostic lymph node extirpation in CUP syndrome - useful or damaging?

OBJECTIVE: In a proportion of patients with cervical lymph node metastasis no primary can be found even with modern imaging and careful clinical examination (cancer of unknown primary syndrome = CUP syndrome). The ideal diagnostic approach is still debated on. METHODS: The clinical data of 75 patients (median age: 61.8 years; 16 females and 59 males), which have been treated for cervical squamous cell carcinoma of unknown primary syndrome in our hospital were retrospectively analyzed. RESULTS: In 12% of patients (n = 9) the primary demarcated in a time period of up to 5.3 years after diagnosis. In the patients who did not receive adjuvant radiotherapy (n = 13), primary became apparent in 38%. Diagnostic lymph node extirpation delayed time until therapeutic neck dissection on average for 3 weeks. In 62% of patients with previous lymph node extirpation (pN2a-N2c), a modified radical neck dissection was required compared to 41% when the surgical site was not operated on. CONCLUSIONS: In 12% of patients' primary demarcated in the course of the disease. A diagnostic lymph node extirpation was compared to direct therapeutic neck dissection after frozen section analysis associated with a three weeks delayed therapy and higher rate of modified radical neck dissection.