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Purpose: To re-statistical analysis of the Pentacam or Corvis ST parameters from literatures, and to obtain more sensitive diagnostic parameters for clinical keratoconus (CKC) and forme fruste keratoconus (FFKC), respectively. Methods: The parameters and the corresponding area of ROC curve (AUC) in previous studies were extracted and screened to obtain the database of CKC (Data-CKC) and FFKC (Data-FFKC), respectively. Two different importance evaluation methods (%IncMSE and IncNodePurity) of random forest were used to preliminary select the important parameters. Then, based on the partial dependency analysis, the sensitive diagnostic parameters that had promotion to the diagnostic performance were obtained. Data-FFKC was analyzed in the same way. Finally, a diagnostic test meta-analysis on the sensitive parameter of interest was conducted to verify the reliability of the above analysis methods.Results: There were 88 parameters with 766 records in Data-CKC, 57 parameters with 346 records in Data-FFKC. Based on two importance evaluation methods, 60 important parameters were obtained, of which 20 were further screened as sensitive parameters of keratoconus, and most of these parameters were related to the thinnest point of cornea. The stiffness parameter at first applanation (SPA1) was the only Corvis ST output parameter sensitive to FFKC except the Tomographic and Biomechanical Index (TBI) and the Corvis Biomechanical Parameter (CBI). A total of 4 records were included in the meta-analysis of diagnostic tests on SPA1. The results showed that there was threshold effect, but no significant heterogeneity (I2=33%), and the area under the SROC curve was 0.87 (95% CI, 0.84-0.90).Conclusions: the sensitive diagnostic parameters of keratoconus mainly include the 7 categories. The diagnostic value of SPA1, which represents the biomechanical properties of cornea, is worthy of further attention in the diagnosis of keratoconus in forme fruste keratoconus. Moreover, the morphological parameters based on the typical position of the thinnest point of corneal thickness have potential special significance for the diagnosis of disease.

Purpose Pachychoroid spectrum disease encompasses a set of macular disorders secondary to an abnormally thick choroid. However, the pathological process underlying pachychoroid spectrum disease and its overlap with age-related macular degeneration (AMD) remain unclear. This review aimed to understand the underlying pathology, classification, and phenotypes of pachychoroid spectrum disease. Methods This comprehensive literature review was performed based on a search of peer-reviewed published papers relevant to the current knowledge of pachychoroid disease spectrum. Results Pachychoroid is primarily a bilateral phenomenon; the main pathological lesions include choriocapillaris attenuation and abnormally dilated pachyvessels. Chronic central serous chorioretinopathy (CSC) and pachychoroid neovasculopathy (PNV) show similar morphological changes and angiogenic cytokine levels. The subretinal fluid in PNV may not accurately indicate PNV activity. Besides, types 1 and 2 of choroidal neovascularization (CNV) may be involved in primary pachychoroidal disease. Both choroidal arteriosclerosis and higher hydrostatic pressure contribute to hyalinized choroidal arteries and aneurysmal dilatations, resulting in PNV progression to polypoidal choroidal vasculopathy (PCV). Thus, pachychoroid-related type 2 CNV and chronic CSC could be considered as PNV (IIIc) and as a precursor of PNV (IIIa), respectively. Tangled PCV on optical coherence tomography angiography that fails to develop aneurysms should be classified as a subtype of PNV or a forme fruste of PCV. Conclusions Multiple disorders of the pachychoroid spectrum are considered as a continuous disease process, ultimately stimulated by choroidal malfunction. PCV overlaps both AMD and pachychoroid disease, especially for thin-choroid and bilateral types. The terminology and classification of pachychoroid spectrum disease should be used cautiously.

Background: To explore the feasibility of corneal morphological and biomechanical parameters for keratoconus and forme fruste keratoconus diagnosis.Methods: This case-control study included a total of 517 eyes from 408 keratoconus patients (KC group), 83 eyes from 83 forme fruste keratoconus patients (FFKC group), and 158 eyes from 158 patients with normal corneas (NL group). All subjects underwent routine ophthalmology examinations. Pentacam and Corneal Visualization Scheimpflug Technology were used to obtain corneal morphological and biomechanical parameters. Differences between the groups were compared using receiver operating characteristic (ROC) curve analysis.Results: Comparison of the NL group with the KC and FFKC groups (PPPConclusion: All corneal morphological and most biomechanical parameters are different in KC versus NL, but only a few parameters are different in FFKC versus NL. BAD-D and TBI have the highest efficiency, sensitivity, and specificity for distinguishing KC from NL. The parameters had a low ability to distinguish FFKC from NL. The application of biomechanical instruments to diagnose early keratoconus needs further study.

The complex phenomenological understanding of dystonia has transcended from the clinics to genetics, imaging and neurophysiology. One way in which electrophysiology will impact into the clinics are cases wherein a dystonic clinical presentation may not be typical or a "forme fruste" of the disorder. Indeed, the physiological imprints of dystonia are present regardless of its clinical manifestation. Underpinnings in the understanding of dystonia span from the peripheral, segmental and suprasegmental levels to the cortex, and various electrophysiological tests have been applied in the course of time to elucidate the origin of dystonia pathophysiology. While loss of inhibition remains to be the key finding in this regard, intricacies and variabilities exist, thus leading to a notion that perhaps dystonia should best be gleaned as network disorder. Interestingly, the complex process has now spanned towards the understanding in terms of networks related to the cerebellar circuitry and the neuroplasticity. What is evolving towards a better and cohesive view will be neurophysiology attributes combined with structural dynamic imaging. Such a sound approach will significantly lead to better therapeutic modalities in the future.

AIM: To explore the significance of corneal epithelial thickness analysis in diagnosing early keratoconus. METHODS: There were 26 clinical keratoconus, 21 forme fruste keratoconus, 40 high corneal astigmatism (ΔK) and 40 low ΔK eyes involved in the study. Fourier-domain optical coherence tomography was used to measure the corneal epithelial thickness of four groups. The morphological features of topographic map and the thickness of corneal epithelial thinnest point were analyzed. The distribution curve of corneal epithelial thickness at 45°, 90°, and 135° axial directions that are through the pupil center was also analyzed. One-way ANOVA was performed to compare the data. RESULTS: The topographic map of forme fruste keratoconus corneal epithelial thickness was uniformity shape; crater shape existed only in clinical keratoconus group; and central island shape mainly existed in high ΔK group. The thinnest point of corneal epithelial thickness of forme fruste keratoconus group was significantly lower than that of low ΔK group (P=0.022). The thickness of corneal epithelium in the forme fruste keratoconus at 90° was thinner than that in the low astigmatism group at -1, and -2 mm points (P-1 mm=0.015, P-2 mm=0.036). CONCLUSION: The analysis of the thinnest point in forme fruste keratoconus corneal epithelium appears earlier than corneal epithelial remodeling. The topographic map of corneal epithelium in high ΔK eyes appears in central island shape, and can be used for the differential diagnosis of early keratoconus.

Background: At present, the diagnosis of keratoconus with Pentacam (typical morphological measurement device), Ocular Response Analyzer (ORA) and Corneal Visualization Scheimpflug Technology (Corvis ST) (two main in vivo biomechanical measurement devices), is mainly for clinical keratoconus (CKC), and the analysis of diagnostic performance is only for the comparison of single output parameters, and the total number of parameters is not complete. Therefore, we intend to use the above three devices to more comprehensively evaluate the ability of the parameters reflecting the morphological and biomechanical properties of the cornea to distinguish keratoconus, especially contralateral normal eye of unilateral keratoconus, that is, the forme fruste keratoconus (FFKC), so as to to obtain further reference for early diagnosis of keratoconus.Methods: Normal eyes (n = 50), CKC eyes (n = 45), and FFKC eyes (n = 15) were analyzed using Pentacam, Corvis ST, and ORA. Stepwise logistic regression of all parameters was performed to obtain the optimal combination model capable of distinguishing CKC, FFKC from normal, named SLR1 and SLR2, respectively. Receiver operating characteristic (ROC) curves were applied to determine the predictive accuracy of the parameters and the two combination models, as described by the area under the curve (AUC). AUCs were compared using the DeLong method. Results: The SLR1 model included only the TBI output by Pentacam, while the SLR2 model included the morphological parameter F.Ele.Th, and two parameters from the Corvis ST, HC DfA, and SP-A1. The majority of the parameters had sufficient strength to differentiate the CKC from normal corneas. Even the seven separate parameters and the SLR1 model had a discrimination efficiency of 100%. The predictive accuracy of the parameters was moderate for eyes with FFKC, and the SLR2 model (0.965) presented an excellent AUC, followed by TBI, F.Ele.Th and BAD-D.Conclusion: The F.Ele.Th from Pentacam was the most sensitive morphological parameter for FFKC, and the combination of F.Ele.Th, HC DfA and SP-A1 made the diagnosis of FFKC more efficient. The CRF and CH output by ORA did not improve the combined diagnosis, despite the corneal combination of morphological and biomechanical properties that optimized the diagnosis of FFKC.

Isolated orofacial clefts (OFC) are common with poorly understood aetiology. Heterogeneous phenotypes and subphenotypes confound aetiological variant findings. To improve OFC phenome understanding, population-based, consecutive, pre-treatment infants with isolated unilateral cleft lip (UCL, n = 183) and isolated cleft palate (CP, n = 83) of similar ancestry were grouped for deep phenotyping. Subphenotypes stratified by gender and cleft severity were evaluated for primary dental malformations and maturation using radiographs. We found that cleft severity and tooth agenesis were inadequate to distinguish heterogeneity in infants with UCL and CP. Both groups featured slow dental maturity, significantly slower in males and the UCL phenotype. In 32.8% of infants with UCL, supernumerary maxillary lateral incisors were present on the cleft lip side, but not in infants with CP, suggesting a cleft dental epithelium and forme fruste cleft dentoalveolus of the UCL subphenotype. The findings underscored the importance of deep phenotyping to disclose occult OFC subphenotypes.

PURPOSE: To identify the definitions used for the terms sub-clinical keratoconus and forme fruste keratoconus in published articles. METHODS: This was a prospective, systematic literature review of the electronic database in PubMed, the Cochrane Library, and LILACS Database of all studies using the keywords “subclinical keratoconus” and/or “forme fruste keratoconus” until August 18, 2017. Two independent reviewers analyzed the data. The inclusion criteria for articles were having analyzed subclinical keratoconus or forme fruste keratoconus eyes with a sample size greater than 10 eyes; containing the definition of subclinical keratoconus or forme fruste keratoconus; and the quality of published reports was assessed using standards quality index methods. The following aspects of the selected articles were then analyzed: inclusion criteria for definition and technology used. RESULTS: A total of 198 and 95 studies, respectively, including the definition of subclinical keratoconus and forme fruste keratoconus were collected in an initial search, of which 165 and 73 studies, respectively, were excluded. Definitions for subclinical keratoconus and forme fruste keratoconus included the criteria of having keratoconus in the fellow eye in 72.72% (24 of 33) and 77.27% (17 of 22) of the articles, respectively. A total of 96.97% (32 of 33) and 90.90% (20 of 22) of the studies used more than one parameter to define subclinical keratoconus and forme fruste keratoconus, respectively. The most common extra parameters included normal slit-lamp examination and cornea on slit-lamp biomicroscopy and inferior-superior asymmetry and/or bowtie pattern with skewed radial axes. CONCLUSIONS: This review demonstrates the lack of unified criteria to define subclinical keratoconus and forme fruste keratoconus. According to the literature review, the most common subclinical keratoconus definition used refers to an eye with topographic signs of keratoconus and/or suspicious topographic findings under normal slit-lamp examination and keratoconus in the fellow eye and the most common forme fruste keratoconus definition refers to an eye with normal topography, normal slit-lamp examination, and keratoconus in the fellow eye. [ J Refract Surg . 2020;36(4):270–279.]

This chapter summarizes multiple points of convergence between chronic kidney disease and kidney senescence to highlight the proposition that both entities are deeply intertwined. Next, I describe geronic proteins using as an example the interactions between endostatin and tissue transglutaminase. I propose that the stress-induced premature senescence of kidney-resident cells constitutes a platform for progression of chronic kidney disease. The description of fate of senescent cells from enforced rejuvenation to a point of no-return or apoptosis follows. Local and systemic effects of senescent cells, including the release of senescence-associated secretory phenotype products, are delineated. The chapter concludes with the recounting of therapeutic strategies to limit the senescent cell burden and, by doing so, arresting the progression of chronic kidney disease.

This International Consensus Classification and Nomenclature for the congenital bicuspid aortic valve condition recognizes 3 types of bicuspid valves: 1. The fused type (right-left cusp fusion, right-non-coronary cusp fusion and left-non-coronary cusp fusion phenotypes); 2. The 2-sinus type (latero-lateral and antero-posterior phenotypes); and 3. The partial-fusion (forme fruste) type. The presence of raphe and the symmetry of the fused type phenotypes are critical aspects to describe. The International Consensus also recognizes 3 types of bicuspid valve-associated aortopathy: 1. The ascending phenotype; 2. The root phenotype; and 3. Extended phenotypes. © 2021 Jointly between the RSNA, the European Association for Cardio-Thoracic Surgery, The Society of Thoracic Surgeons, and the American Association for Thoracic Surgery. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. All rights reserved. Keywords: Bicuspid Aortic Valve, Aortopathy, Nomenclature, Classification.

We report the case of a female, 77 year old patient with multi-localized skin infarctions following vaccination with mRNA-1273 (Moderna). This phenomenon is to our knowledge otherwise only seen in infection-associated purpura fulminans - which was thoroughly ruled out in our patient. This report demonstrates that we need to be vigilant of a wider array of vascular phenomena related to Covid vaccinations.

Corneal surface analysis is now more and more accurate. Corneal topography is a gold standard in corneal pathology follow-up: keratoconus, corneal grafts, orthokeratology. In refractive surgery, cornea ectasia post-Lasik must be avoided. Analyzing anterior and posterior surface can detect forme fruste keratoconus FFKC. Topography allows also better predictability of premium intraocular implants surgery. Topography is key examination and its interpretation is essential.

Graphical abstract, Highlights • Cor triatriatum dexter (CTD) can complicate percutaneous atrial septal interventions. • Clinically silent (forme fruste) CTD is detectable by new echocardiography techniques. • Using these techniques could improve patient selection and guide interventions.

Keratoconus is a chronic disorder of the cornea, characterized by its progressive thinning, stretching, and conical protrusion. Diagnostics of subclinical keratoconus, as well as its early stages (forme fruste), is a complex problem. The presence of these forms of keratoconus in a patient is one of the reasons for the development of keratectasia after laser refractive surgery. Currently, the role of genetic factors in keratoconus development has been proven. This indicates the possibility of diagnostics of subclinical and forme fruste keratoconus using genetic markers. Knowledge about the patient's genetic susceptibility to keratoconus would allow correcting the tactics of treatment of refractive anomalies and avoiding serious side effects. The studies of causal mutations indicate the genetic heterogeneity of keratoconus, which complicates the development of a diagnostic panel. Selection of candidate variants from the currently known ones based on clear criteria may be one of the approaches for diagnostic markers search. In this review, we have analyzed articles on keratoconus markers in order to form a list of candidate variants for genotyping in the Russian population. The selection criteria took into account the complexes of symptoms in which a marker was found, populations in which a particular marker was investigated, the presence and results of replication studies. The analysis included markers in VSX1, SOD1, ZEB1, LOX, CAST, DOCK9, TGFBI, HGF, MAP3K19, KCND3, COL4A3, COL4A4, COL5A1, FNDC3B, FOXO1, BANP-ZNF469, MPDZ-NF1B, WNT10A genes. Based on the results of the analysis, the following candidate variants were selected for genotyping in the Russian population of patients with keratoconus: rs1536482 and rs7044529 in the COL5A1 gene, rs5745752 and rs2286194 in the HGF gene, rs4954218 in the MAP3K19 gene, rs4839200 near the KCND3 gene, rs2721051 near the FOXO1 gene, rs1324183 between the MPDZ and the NF1B genes, and rs121908120 in the WNT10A gene.Keratokonus – éto khronicheskoe zabolevanie rogovitsy, kharakterizuiushcheesia ee progressiruiushchim istoncheniem, ee rastiazheniem i konusovidnym vypiachivaniem. Diagnostika subklinicheskogo keratokonusa, a takzhe ego rannikh stadiĭ (forme fruste) predstavliaet soboĭ slozhnuiu problemu. Nalichie dannykh form keratokonusa u patsienta iavliaetsia odnoĭ iz prichin razvitiia keratéktaziĭ posle lazernykh refraktsionnykh vmeshatel'stv. V nastoiashchee vremia dokazana rol' geneticheskikh faktorov v razvitii keratokonusa. Éto ukazyvaet na vozmozhnost' razrabotki diagnostiki subklinicheskoĭ formy i forme fruste keratokonusa s pomoshch'iu geneticheskikh markerov. Znanie o geneticheskoĭ predraspolozhennosti k keratokonusu u patsienta pozvolilo by skorrektirovat' taktiku lecheniia refraktsionnykh anomaliĭ i izbezhat' tiazhelykh pobochnykh éffektov. Issledovaniia kauzal'nykh mutatsiĭ svidetel'stvuiut o geneticheskoĭ geterogennosti keratokonusa, chto zatrudniaet razrabotku diagnosticheskoĭ paneli. Odnim iz podkhodov k poisku diagnosticheskikh markerov mozhet byt' otbor kandidatnykh variantov iz izvestnykh na dannyĭ moment na osnovanii chetkikh kriteriev. V dannom obzore byli proanalizirovany raboty, posviashchennye izucheniiu markerov keratokonusa, kotorye pozvoliat sformirovat' spisok kandidatnykh variantov dlia genotipirovaniia v rossiĭskoĭ populiatsii. Kriterii otbora uchityvali kompleksy simptomov, pri kotorykh obnaruzhivalsia marker, populiatsii, v kotorykh byl issledovan tot ili inoĭ marker, a takzhe nalichie i rezul'taty replikatsionnykh issledovaniĭ. V analiz byli vkliucheny markery v genakh VSX1, SOD1, ZEB1, LOX, CAST, DOCK9, TGFBI, HGF, MAP3K19, KCND3, COL4A3, COL4A4, COL5A1, FNDC3B, FOXO1, BANP-ZNF469, MPDZ-NF1B, WNT10A. Po rezul'tatam analiza otobrany sleduiushchie kandidatnye varianty dlia genotipirovaniia v rossiĭskoĭ populiatsii patsientov s keratokonusom: rs1536482 i rs7044529 v gene COL5A1, rs5745752 i rs2286194 v gene HGF, rs4954218 v gene MAP3K19, rs4839200 vblizi gena KCND3, rs2721051 vblizi gena FOXO1, rs1324183, raspolozhennyĭ mezhdu genami MPDZ i NF1B, i rs121908120 v gene WNT10A.

Purpose:To determine the diagnostic accuracy of corneal biomechanical factors in differentiating patients with forme fruste keratoconus (FFKC) from astigmatic and normal cases.Methods:A total of 50 eyes with FFKC, 50 with astigmatism and 50 normal eyes, were included in this study. All patients had a detailed ophthalmologic examination including slit-lamp evaluation, Goldmann tonometry, indirect fundoscopy, topography by Scheimpflug imaging biomicroscopic anterior and posterior segment examination, and corneal biomechanical and intraocular pressure evaluation with ocular response analyzer (ORA).Results:All topographic findings were statistically significant among the three groups (P>0.05). Although there was no statistically significant difference in the corneal-compensated intraocular pressure (IOPcc) among the three groups, the Goldmann-correlated intraocular pressure (IOPg), corneal hysteresis (CH), and corneal resistance factor (CRF) were statistically significantly lower in the FFKC group, compared with the other groups (P

Umbilical cord blood (UCB) is the preferred donor cell source for children with Hurler syndrome undergoing transplant, and its use has been associated with improved “engrafted survival” rates. However, as in other pediatric recipients of UCB transplants for nonmalignant disease, immune-mediated cytopenia (IMC) is a significant complication. This article describes 8 episodes of IMC in 36 patients with Hurler syndrome undergoing UCB transplant. The incidence of IMC was increased in those with a higher preconditioning absolute lymphocyte count and in those conditioned with fludarabine-containing regimens rather than cyclophosphamide, and it included red cell alloantibodies directed at cord blood group antigens that are novel to the recipient. In several cases, IMC was a precursor to immune-mediated complete graft rejection. We describe IMC as part of a spectrum of graft rejection by a residual competent host immune system and a forme fruste of complete graft rejection.

Yuceer, Hande/0000-0001-9027-5291; Benbir Senel, Gulcin/0000-0003-4585-2840; BAKIRCIOGLU DUMAN, Ezgi/0000-0002-1912-8325 WOS:000470851600013 PubMed ID: 31543789 Morvan syndrome (MoS) is typically characterized by neuromyotonia, sleep dysfunction, dysautonomia, and cognitive dysfunction. However, MoS patients with mild peripheral nerve hyperexcitability (PNH) or encephalopathy features have been described. A 46-year-old woman presented with a 2-month history of constipation, hyperhidrosis, and insomnia. Neurologic examination revealed muscle twitching and needle electromyography showed myokymic discharges in all limbs. No clinical or electrophysiological features of neuromyotonia were present. Although the patient denied any cognitive symptoms, neuropsychological assessment revealed executive dysfunction, while other cognitive domains were preserved. Cranial and spinal MRIs were unrevealing and tumor investigation proved negative. Polysomnography examination revealed total insomnia, which was partially reversed upon immune-modulatory therapy. Investigation of a broad panel of antibodies revealed serum leucine-rich glioma inactivated protein 1 and contactin-associated protein 2 antibodies. The features of this case indicate that the presentation of PNH syndromes may show significant variability and that MoS patients may not necessarily exhibit full-scale PNH and encephalopathy symptoms. (C) 2019 The Author(s) Published by S. Karger AG, Basel

Patients with autoimmune encephalitides, especially those with antibodies to the N-methyl-d-aspartate receptor (NMDAR), often present with prominent psychosis and respond well to immunotherapies. Although most patients progress to develop various neurological symptoms, it has been hypothesised that a subgroup of patients with first-episode psychosis (FEP) suffer from a forme fruste of autoimmune encephalitis. Without accurate identification, this immunotherapy-responsive subgroup may be denied disease-modifying treatments. Thirty studies addressing aspects of this hypothesis were identified in a systematic review. Amongst other shortcomings, 15/30 reported no control group and only 6/30 determined cerebrospinal fluid (CSF) autoantibodies. To ourselves address these—and other—limitations, we investigated a prospectively ascertained clinically well-characterised cohort of 71 FEP patients without traditional neurological features, and 48 healthy controls. Serum and CSF were tested for autoantibodies against seven neuronal surface autoantigens using live cell-based assays. These identified 3/71 (4%) patient sera with weak binding to either contactin-associated protein-like 2, the NMDAR or glycine receptor versus no binding from 48 control samples (p = 0.28, Fisher’s test). The three seropositive individuals showed no CSF autoantibodies and no differences from the autoantibody-negative patients in their clinical phenotypes, or across multiple parameters of peripheral and central inflammation. All individuals were negative for CSF NMDAR antibodies. In conclusion, formes frustes of autoimmune encephalitis are not prevalent among FEP patients admitted to psychiatric care. Our findings do not support screening for neuronal surface autoantibodies in unselected psychotic patients.

Purpose To present a descriptive system for the elliptic demarcation area seen in keratoconus densitometry maps (obtained with a Scheimpflug tomographer) and to evaluate its suitability for clinical practice. Methods The subjects were 30 keratoconus patients at different stages and 20 healthy subjects. The averaged densitometry maps ('two-layers' scan, with fixed layers 120 mu m and endothelium) were analysed using a system of four categories (termed 'Brightness', 'Contrast', 'Decentration' and 'Octants surrounded by a dark line') that we created to characterise the demarcation area. Four examiners (three corneal specialists and one junior resident) used the system to classify the maps. The inter-rater agreement was calculated for two subgroups: (1) clinical keratoconus patients and (2) both healthy patients and forme fruste keratoconus patients. Intra-rater agreement was also determined. Results Inter-rater agreement on classification was higher when analysing clinical keratoconus, reaching levels of substantial agreement. Despite this, only low levels of agreement were found in 'Decentration', penalized due to the skewness in the distribution of this descriptor. Almost perfect intra-rater agreement was obtained for all descriptors in the first subgroup of clinical keratoconus, whereas the agreement was generally moderate within the second subgroup of normal and forme fruste eyes. Agreement was slightly lower with the less experienced observer. At least three observers agreed on four forme fruste keratoconus eyes presenting abnormalities in the images. The observers reported that the 'Brightness' descriptor was subjective and redundant with 'Contrast'. Conclusions The description of the area was repeatable and reproducible, and may be a valuable supplement when documenting clinical keratoconus stage and progression in daily practice. However, a minor learning curve was noticed and agreement was higher among the more experienced observers. Since the descriptor 'Brightness' was found to be subjective and redundant, it was excluded from the final proposed classification.

Shone’s anomaly, a congenital cardiac malformation complex, consists of multiple levels of left heart obstruction. A rare case of an incomplete form of this anomaly discovered incidentally during cardiac catheterization for an unrelated event is described.

Introduction: Bicuspid aortic valve (BAV) is a common congenital heart defect associated with coronary artery (CA) variants, including higher incidence of left CA dominance and shorter left main CA length. In patients with right-left fusion (R/L) BAV, we observed that the origins of left and right coronaries are in closer proximity than in normal patients. ‘Forme fruste’ types of R/L BAV are subtle and difficult to diagnose, hence this coronary pattern can aid in diagnosis. We defined intercoronary distance as the angle separating the left and right coronary ostia relative to the aortic valve center. Hypothesis: The coronary angle is more acute in R/L BAV than in normal aortic valves. Methods: A retrospective review of pediatric echocardiograms with R/L BAV at a single institution (12/2010-11/2018) was performed; coronary angles were measured and compared to age-matched controls. Those with inadequate images or anomalous coronary origins were excluded. Results: We identified 193 patients with R/L BAV (64% male) and 136 patients with normal aortic valves (57% male). Coronary angle was significantly more acute in R/L BAV than in controls (117.7°±16.8° vs 139.0°±10.1°, p Conclusions: Coronary origins are in closer proximity in R/L BAV independent of annulus/root geometry, associated cardiac defects, age, or gender. This new finding may assist in echocardiographic diagnosis of subtle subtypes of BAV.

Purpose To investigate the utility of biomechanical property measurements using a Scheimpflug-based tonometer (SBT) and/or anterior segment optical coherence tomography (AS-OCT) for diagnosing forme fruste keratoconus (FFK). Methods In this retrospective interventional case series, 23 eyes with FFK of 23 consecutive patients and 52 eyes of 52 healthy volunteers who visited our keratoconus outpatient clinic were enrolled. Logistic regression analysis was conducted to determine the causal relationship between FFK diagnosis and each parameter. Results When only SBT was used, the corneal stiffness parameter, stiffness parameter A1 (SP-A1) and the corneal velocity at first applanation were selected as explanatory variables, and sensitivity, specificity and area under the receiver operating characteristic curve (AUROC) were 82.9%, 86.9% and 0.938, respectively. When only AS-OCT parameters were used, the posterior corneal asymmetric component and central corneal thickness were selected, and the sensitivity, specificity and AUROC were 82.6%, 94.2% and 0.893, respectively. When parameters from both methods were used, SP-A1 and the posterior corneal asymmetry component derived from Fourier analysis were selected as explanatory variables, and sensitivity, specificity and AUROC were 91.30%, 90.38% and 0.947, respectively. No significant differences in AUROC were observed between diagnoses using each device and the combination of both devices (AS-OCT versus SBT, p = 0.314; integrated parameters versus AS-OCT, p = 0.081; integrated parameters versus SBT, p = 0.234). Conclusion Optimization of SBT and AS-OCT parameters allowed for the diagnosis of FFK at a clinically usable level. Forme fruste keratoconus (FFK) diagnosis integrating biomechanical properties with AS-OCT showed no superiority compared to diagnosis based on a single device.

PURPOSE: To assess the diagnostic values of corneal epithelial and stromal thickness distribution characteristics in forme fruste keratoconus (FFKC) and subclinical keratoconus (KC). METHODS: This cross-sectional study was conducted at VISSUM Innovation and Miguel Hernandez University, Alicante, Spain. Twenty-seven eyes (27 subjects) with FFKC, 50 eyes (50 subjects) with subclinical KC with a best spectacle corrected distance visual acuity ?20/20 (Snellen) (grade zero KC according to the Red Temática de Investigación Cooperativa en Salud classification), and 66 control eyes (66 subjects) were included. Epithelial and stromal thicknesses and epithelium/stroma (E/S) thickness ratio at center, thinnest point, 5-, and 8-mm circles obtained from the MS-39 device (CSO, Firenze, Italy) were compared among the control, FFKC, and subclinical KC groups. RESULTS: The FFKC group had thinner 8-mm superior-nasal epithelium and higher central E/S ratio compared with the control group (P < 0.05). In the subclinical KC group, the E/S ratios in the 5-mm temporal and superior zones were higher than those in the control group (P < 0.05). The FFKC and subclinical KC groups had thinner stroma compared with the control group (P < 0.05). A two-parameter formula correctly classified 94% of the eyes with subclinical KC and 98.5% of the normals, whereas another three-parameter model had 75% sensitivity and 94.3% specificity for discriminating FFKC from normals. CONCLUSIONS: This study identified different epithelial distributional and behavioral patterns in eyes with FFKC and subclinical KC. Eyes with FFKC seem to have increased central E/S ratio and asymmetric superior-nasal epithelial thinning, whereas keratometric and volumetric alterations seem to be more prominent in subclinical KC.

We report 16 patients of tinea cruris who presented with an asymptomatic red scrotum due to fixed dose combination creams containing antifungal agents and topical steroids applied to the thighs as a treatment of tinea cruris. The erythema resolved upon starting appropriate treatment with single molecule antifungal creams and oral antifungal drugs in about six weeks' time in majority of cases. We propose that this clinical presentation may be akin to red scrotum syndrome (RSS). Due to its asymptomatic nature in most of the cases, we propose that this could be a forme fruste of RSS.

Keratoconus (KC) is an ectatic disorder with a high prevalence rate. However, the exact cause of the disease and possible underlying mechanisms of development remain unclear. In this present study, we aimed to investigate the anterior and the posterior corneal surface area in normal, forme fruste keratoconus (FFKC), and keratoconic eyes (as a reference group) using anterior segment optical coherence tomography (AS-OCT) in order to assess the pathological change of KC. The surface areas of the anterior or posterior cornea, and the anterior-posterior (As/Ps) ratio of corneal surface area, were measured at the central 5.0 mm-, 6.0 mm-, and 7.0 mm-diameter areas via AS-OCT, and a comparison between the normal eyes and FFKC eyes was then performed using the Mann-Whitney U test. The posterior surface area at the central 5.0 mm areas in the FFKC eyes (20.430 mm2) and KC eyes (20.917 mm2) seemed to become larger than that of normal eyes (20.389 mm2) (normal vs FFKC; P = 0.06). Moreover, the As/Ps of the corneal surface area in the FFKC eyes (0.986) and the KC eyes (0.976) was significantly smaller than that of the normal eyes (0.988) (normal vs FFKC; P

Primary melanocytic tumors of central nervous system represent rare tumors arising from melanocytes of the leptomeninges. These neoplasms include focal forms like melanocytoma and primary malignant melanoma and diffuse forms like leptomeningeal melanocytosis and primary leptomeningeal melanomatosis. The clinical diagnosis remains challenging, with clinical and radiologic features overlapping with other more common diseases. Here we present a case of a 38 years old male with primary diffuse leptomeningeal melanomatosis with presence of a NRASQ61K mutation without features of neurocutaneous melanosis.

Miller Fischer syndrome (MFS) is a variant of Guillain-Barré syndrome first described in 1956 and is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia. However, since its discovery, forme fruste and overlapping syndrome have been described. A forme fruste of MFS implies an attenuated form where not all of the clinical triad are present. In this report, a case of MFS is highlighted that was mistakenly treated as posterior circulation stroke, as well as the challenges faced in reaching the correct diagnosis and hence the appropriate treatment.

Purpose: To enhance the current standards of subclinical keratoconus screening based on the statistical modeling of the pixel intensity distribution of Scheimpflug images. Methods: Scheimpflug corneal tomographies corresponding to 25 corneal meridians of 60 participants were retrospectively collected and divided into three groups: controls (20 eyes), subclinical keratoconus (20 eyes), and clinical keratoconus (20 eyes). Only right eyes were selected. After corneal segmentation, pixel intensities of the stromal tissue were statistically modeled using a Weibull probability density function from which parameter a (pixel brightness) was derived. Further, data were transformed to polar coordinates, smoothed, and interpolated to build a map of the corneal a parameter. The discriminative power of the method was analyzed using receiver operating characteristic curves. Results: The proposed platform-independent method achieved a higher performance in discriminating subclinical keratoconus from control eyes (90.0% sensitivity, 95.0% specificity, 0.97 area under the curve [AUC]) than the standard method (Belin–Ambrósio enhanced ectasia display), which uses only corneal morphometry (85.0% sensitivity, 85.0% specificity, 0.80 AUC). Conclusions: Analysis of light backscatter at the cornea successfully discriminates subclinical keratoconus from control eyes, upgrading the results previously reported in the literature. Translational Relevance: The proposed methodology has the potential to support clinicians in the detection of keratoconus before showing clinical signs. © 2021 The Authors.

The term ‘keratoconus (KC) suspect’ is used as a blanket term to refer to any deviation of virgin cornea shape toward KC features. We intend to subclassify such topographies in meaningful and informative designations. Pentacam corneal topographies of 199 consecutive refractive surgery candidates (398 eyes) are examined. Features of steepness, inferior–superior asymmetry, focal steepening, thinning, and bounded anterior or posterior elevations are observed in the quad map. Scissoring on retinoscopy, loss of best spectacle-corrected visual acuity, and iron ring deposition were looked for. Through iterative observation and refinement of classification criteria—partly taken from the literature—all eyes were designated a specific topographic diagnosis, i.e., circumventing the usage of the expression KC ‘suspect’. Topographies of 308, 48, 21, 13, 6, 1, and 1 (collectively 398 eyes) were designated: normal, ‘atypical normal,’ forme fruste KC, posterior KC, subclinical/mild KC, superior KC, and pseudo–KC, respectively. Current imaging modalities of the cornea and our accumulated experience in refractive science allow assignment of distinctive designations for abnormal corneal shapes along the topography spectrum. We devised and used the expressions: normal, atypical normal, forme fruste (arrested-incomplete) KC, posterior KC, subclinical (active latent) KC, superior KC, and pseudo-keratoconus. Identification of 1.5% (mild) KC highlights the importance of screening for ultraviolet cross-linkage candidacy in refractive surgery referrals.

GLI3 mutations are known to be associated with nine syndromes/conditions in which polydactyly is a feature. In this review, the embryology, pathogenesis, and animal models of GLI3-related polydactyly are discussed first. This is followed by a detailed review of the genotype-phenotype correlations. Based on our review of the literature and our clinical experiences, we recommend viewing GLI3-related syndromes/conditions as four separate entities; each characterized by a specific pattern of polydactyly. These four entities are: the preaxial polydactyly type IV-Greig-acrocallosal spectrum, postaxial polydactyly types A/B, Pallister-Hall syndrome (PHS), and oral-facial-digital overlap syndrome. We also provide illustrative clinical examples from our practice including a family with a novel GLI3 mutation causing PHS. The review also introduces the term 'Forme Fruste' preaxial polydactyly and gives several conclusions/recommendations including the recommendation to revise the current criteria for the clinical diagnosis of PHS.

Spontaneous perforation of choledochal cyst (CDC) is rare with an incidence of 1.8%–7%. Perforation with pseudocyst formation is even rarer, there being only two case reports. We report the first case of antenatal perforation of CDC with biliary pseudocyst formation in a newborn and its management.