Visual Function and Neuropsychological Profiling of Idiopathic Infantile Nystagmus.

Though considered a benign condition, idiopathic infantile nystagmus (IIN) may be associated with decreased visual acuity and oculo-motor abnormalities, resulting in developmental delays and poor academic performance. Nevertheless, the specific visual function profile of IIN and its possible impact on neuropsychological development have been poorly investigated. To fill this gap, we retrospectively collected the clinical data of 60 children presenting with IIN over a 10-year period (43 male; mean age of 7 years, range of 2 months-17 years, 9 months). The majority of the subjects in our cohort presented with reduced visual acuity for far distances and normal visual acuity for near distances, associated with oculo-motor abnormalities. The overall scores of cognitive and visual-cognitive tests were in the normal range, but revealed peculiar cognitive and visual-cognitive profiles, defined by specific frailties in processing speed and visual-motor integration. The same neuropsychological profiles characterize many neurodevelopmental disorders and may express a transnosographic vulnerability of the dorsal stream. As the first study to explore the neuropsychologic competencies in children with IIN, our study unveils the presence of subclinical frailties that need to be addressed to sustain academic and social inclusion.

Acute coronary syndrome after initiation of amoxicillin/clavulanate.

We report the case of a 54 year old man referred to the Emergency Department for rapid onset of an itchy rash and oppressive epigastric pain after assumption of amoxicillin/clavulanate. Electrocardiogram aand laboratory findings were consistent with acute coronaty syndrome. After coronary angiography, diagnosis of type II Kounis syndrome was made.

The role of hypochlorous acid in the management of eye infections: a case series.

Experiences from clinical practice suggest that hypochlorous acid (HOCl) used as adjuvant treatment can shorten the time to clinical resolution of blepharitis, particularly in relation to the ophthalmic complications that often occur with a blepharitis diagnosis. In addition, in clinical practice, HOCl adjuvant treatment also resulted in a viable option for the management of ophthalmic disorders other than blepharitis. This case series presents and discusses real-life experiences with using an HOCl ophthalmic spray to manage eye infections, further characterizing the use of HOCl for ophthalmic applications.

Fishhook Injury to the Upper Eyelid: A Novel Surgical Approach.

BACKGROUND: Fishhook injuries are an uncommon trauma, and removing a penetrating fishhook is a complicated maneuver, especially if the wound involves delicate anatomical structures like the ocular region. DISCUSSION: Several techniques that have been discussed in literature are reviewed and the authors present a novel approach that has been successfully performed on a patient with a fishhook penetrating his upper eyelid after a fishing accident. CONCLUSION: Emergency physicians should be aware of all the possible approaches to fishhook penetrating injuries. If the fishhook does not involve the globe and an ophthalmologist is not available, the injury may be managed in the emergency department.

RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study.

Purpose: To investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene. Methods: This longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements. The data, including imaging, were collected using an electronic clinical research form and were reviewed at a single center to improve consistency. Results: From an overall cohort of 60 Italian patients with RPE65-associated IRD, 43 patients (mean age, 27.8 ± 19.7 years) were included and showed a mean BCVA of 2.0 ± 1.0 logMAR. Time-to-event analysis revealed a median age of 33.8 years and 41.4 years to reach low vision and blindness based on BCVA, respectively. ERG (available for 34 patients) showed undetectable responses in most patients (26; 76.5%). OCT (available for 31 patients) revealed epiretinal membranes in five patients (16.1%). Central foveal thickness significantly decreased with age at a mean annual rate of -0.6%/y (P = 0.044). We identified 43 different variants in the RPE65 gene in the entire cohort. Nine variants were novel. Finally, to assess genotype-phenotype correlations, patients were stratified according to the number of RPE65 loss-of-function (LoF) alleles. Patients without LoF variants showed significantly (P < 0.05) better BCVA compared to patients with one or two LoF alleles. Conclusions: We described the natural course of RPE65-associated IRD in an Italian cohort showing for the first time a specific genotype-phenotype association. Our findings can contribute to a better management of RPE65-associated IRD patients.

Optical coherence tomography angiography in healthy children: A comparison of macular structure.

PURPOSE: The purpose of the present study was to investigate the perfusion density (PD) of macular superficial (SCP) and deep capillary plexus (DCP), the size of foveal avascular zone (FAZ) and central macular thickness (CMT) in healthy children using optical coherence tomography angiography (OCT-A). PATIENTS AND METHODS: About 206 eyes of 111 children were analyzed. The correlation of gestational age (GA), birth weight (BW), age, sex, refractive errors, and visual acuity (VA) with OCT-A parameters were investigated. RESULTS: The mean PD of the fovea and the mean FAZ area of SCP were 17.1% (DS: 4.26) and 234.47 (DS: 106.39) µm2. The mean PD of the fovea and the mean FAZ area of DCP were 13.5% (DS: 5.23) and 298.32 (DS: 112.37) µm2. Superficial and deep FAZ areas were not correlated with sex, age, BW, refractive errors, or VA. FAZ area of SCP was correlated with foveal PD (r = -0.76) and with CMT (r = -0.68). FAZ area of DCP was correlated with foveal's PD (r = -0.61). There was no correlation between CMT and refractive errors. CONCLUSION: OCT-A may provide a non-invasive and reliable approach to evaluate macular perfusion in children. As the FAZ area, PD, and CMT change during the growth period, we performed established a reference range for different ages.

Evaluation of macular and optic nerve head parameters in amblyopic eyes: An optical coherence tomography study.

PURPOSE: To evaluate morphological differences in retinal nerve fibers layers (RNFL), optic nerve head (ONH), ganglion cell complex (GCC), and macular thickness between amblyopic and normal eyes from spectral domain optical coherence tomography (SD-OCT). METHODS: Of 234 eyes of 117 children, four groups emerged: group A (162 eyes of 81 non-amblyopic subjects); group B (32 fellow eyes of 32 subjects with monolateral amblyopia); group C (32 amblyopic eyes of 32 subjects affected by monolateral amblyopia); group D (8 amblyopic eyes of 4 subjects with bilateral amblyopia). Patients underwent SD-OCT for ONH parameters, RNFL, GCC and macular thickness, retina map, and ONH scan quality index (SQI). Two-sided p values <0.05 were taken as statistically significant. (Analysis: STATA v.13). RESULTS: Parameters with a significant difference between groups (p < 0.005) with their Standard Deviation (SD) are presented: rim area, 2.08 (0.49) mm2 in group A and 1.76 (0.68) mm2 in group C; disk area, 2.43 (0.45) mm2 in group A and 2.02 (0.71) mm2 in group C; central macular thickness, 250.99 (19.74) µm in group A and 267.16 (23.52) µm in group C; nerve fiber ONH SQI, 62.82 (13.15) in group A, 51.26 (15.55) in group C, 48.29 (14.37) in group D; retina map SQI, 63.34 (10.34) in group A and 57.34 (9.84) in group C. For other parameters no significant difference was observed (p > 0.005). CONCLUSIONS: Amblyopia may influence optic nerve morphology, central macular thickness, and OCT scan quality. RNFL and GCC are not affected by monolateral amblyopia.

Visual Evoked Potentials in Joubert Syndrome: A Suggested Useful Method for Evaluating Future Approaches Targeted to Improve Visual Pathways' Function.

INTRODUCTION: Joubert syndrome (JS) is a recessive disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features including optic nerve morphologic abnormalities. The function of the visual pathways, including the optic nerve, can be objectively evaluated by visual evoked potential (VEP) recordings. Our work aims to employ VEP to evaluate the neural conduction along the visual pathways in JS patients with or without optic nerve morphologic abnormalities (ONMA). METHODS: In this observational and prospective study, 18 children with genetic diagnosis of JS (mean age 8.78 ± 5.87 years) and 17 healthy age-similar control subjects (control group, 9.05 ± 6.02 years) were enrolled. Based on presence/absence of ONMA at fundus examination, JS patients were divided into two groups: the JS-A group (eight patients with ONMA) and JS-N group (ten patients without ONMA). Following the ISCEV standards, pattern VEPs were recorded in patients and controls in response to 60' and 15' checks to obtain a prevalent activation of large or small axons, respectively. RESULTS: Compared to controls, both the JS-A and JS-N groups showed significant abnormalities in 60' and 15' VEP implicit time and amplitude. Only in the JS-N group were values of 15' VEP implicit significantly correlated with the corresponding values of visual acuity. CONCLUSIONS: Our results suggest that a visual pathways dysfunction (of both large and small axons) detectable by VEP may occur in JS patients regardless of the presence of ONMA. Since clinical trials are envisaged in the near future to address JS-related ocular problems, our results might provide information about the potential usefulness of VEP recordings to assess the efficacy of treatments targeted to improve the visual pathways' function.

Electroretinographic Assessment in Joubert Syndrome: A Suggested Objective Method to Evaluate the Effectiveness of Future Targeted Treatment.

INTRODUCTION: Joubert syndrome (JS) is an autosomal recessive disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features including congenital retinal dystrophy. The function of different retinal elements (rod, cone, bipolar cells) can be objectively evaluated by electroretinogram (ERG) recordings. Our work aims to evaluate the retinal function (by ERG recordings) in patients with JS with or without congenital retinal dystrophy. In addition, since clinical trials should be performed in the near future in JS, our results could provide information about the possible usefulness of ERG recordings in the assessment of the efficacy of treatments targeted to improve the retinal involvement. METHODS: In this observational and prospective study, 24 children with genetic identification for JS (mean age 10.75 ± 6.59 years) and 25 healthy age-similar normal control subjects (control group, mean age 10.55 ± 3.76 years) were enrolled. On the basis of the presence/absence of retinal dystrophy at fundus examination, patients with JS were divided into two groups: patients with JS with retinal dystrophy (16 children, mean age 11.00 ± 6.74 years, providing 16 eyes; JS-RD group) and patients with JS without retinal dystrophy (8 children, mean age 10.50 ± 6.45 years, providing 8 eyes; JS-NRD group). In patients with JS and controls, visual acuity (VA), dark-adapted, light-adapted, and 30-Hz flicker ERGs were performed according to International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. RESULTS: When compared to controls, patients in the JS-RD and JS-NRD groups showed significant abnormalities of the values of dark-adapted, light-adapted, and 30-Hz flicker ERG parameters. The ERG and VA changes were not significantly correlated. CONCLUSIONS: Our results suggest that a dysfunction of photoreceptors and bipolar cells occurs in patients with JS with or without retinal dystrophy. The retinal impairment can be detected by ERG recordings and this method should be proposed to evaluate the effectiveness of adequate treatment targeted to improve the retinal impairment in patients with JS.

Screening and Follow-Up of Acute ROP: Reproducibility of Fluorescein Angiography.

INTRODUCTION: Binocular indirect ophthalmoscopy (BIO) is fundamental for screening of retinopathy of prematurity (ROP). Digital retinal imaging devices with fluorescein angiography (FA) proved to be useful in screening and management of ROP. FA provides valuable additional information that is not detectable through ophthalmoscopy. FA images are relatively easy to interpret even by personnel without specific experience in ROP. The aim of this study is to evaluate reproducibility of FA for the screening and follow-up of ROP. METHODS: A total of 106 pairs of FA images of 30 eyes of 15 premature infants with stage II ROP were evaluated by 5 ophthalmologists: 2 experts, 2 non-experts, and 1 expert in reading FA in adult patients. Each operator gave a score to each of following parameters: leakage, ischemic areas, peripheral plus disease and vascular anomalies. The images were reviewed twice. Intra- and inter-concordance between the readers of the FA findings was evaluated by the means of Cohen's kappa coefficient (κ). RESULTS: The intra-operator concordance was very good (κ > 0.81) for all FA findings. Inter-operator concordance was good (κ > 0.41) for all operators and all FA findings. Global concordance was: substantial (intra-inter readers: κ > 0.61) for leakage, ischemic areas, and plus disease; almost perfect (κ > 0.81) for vascular anomalies; and moderate (κ = 0.41-0.60) for continuity/discontinuity of the ischemic areas. Total FA score was directly correlated to the percentage of treatment: a score ≥ 7 was correlated with 100% treatment and a score ≤ 3 with no treatment. Treatment timing was inversely correlated to FA score: a score ≥ 8 was correlated with a timely treatment (≤ 6 days), and a score ≤ 7 was correlated with a delayed treatment (< 10 days). CONCLUSION: This study showed that FA represents a reproducible imaging technique. It is useful for detecting ROP progression, and to define the treatment timing and type.

Procalcitonin, white blood cell count and C-reactive protein as predictors of S. aureus infection and mortality in infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is characterized by high rates of in-hospital death, and Staphylococcus aureus infection predicts a worse prognosis. We aimed to assess if admission inflammatory biomarkers (white blood cell - WBC - count, C-reactive protein - CRP, and procalcitonin) are informative on microbiological etiology and short-term outcomes. METHODS: Data from 236 patients admitted for IE from January 2013 to June 2018 were retrieved from a multicenter registry. RESULTS: Fifty-two patients (22%) were infected by S. aureus. WBC, CRP and procalcitonin had area under the curve (AUC) values for S. aureus infection of 0.595, 0.675, and 0.727, respectively. Adding procalcitonin to WBC improved discrimination over WBC alone (p = 0.045), and procalcitonin predicted S. aureus infection independently from the other inflammatory biomarkers and patient characteristics. Patients with WBC ≥ 12,800/mm3, CRP ≥ 130 mg/L, and procalcitonin ≥ 1.7 ng/mL had an almost 20-fold higher risk of S. aureus infection than patients with all biomarkers < cut-offs. AUC values for in-hospital death were 0.702, 0.725 and 0.727 for the WBC, CRP, and procalcitonin, respectively. Among inflammatory biomarkers, WBC and procalcitonin independently predicted in-hospital death. Procalcitonin refined risk stratification when added to WBC, and to the combination of WBC and CRP. Patients with WBC ≥ 10,535/mm3, CRP ≥ 85 mg/dL, and procalcitonin ≥ 0.4 ng/mL had a 27-fold higher risk of in-hospital death than patients with all biomarkers < cut-offs. CONCLUSIONS: Among patients with IE, high levels of inflammatory biomarkers on admission, particularly procalcitonin, are associated with a higher likelihood of S. aureus infection, and a higher risk of in-hospital mortality.

Macular staphyloma in patients affected by Joubert syndrome with retinal dystrophy: a new finding detected by SD-OCT.

PURPOSE: Joubert syndrome (JS) is an inherited autosomal recessive or X-lined disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features. It is estimated that retinal dystrophy is present in association with the typical neurological findings in about one-third of the patients. The aim of this study is to better characterize the macular region in JS patients with and without retinal dystrophy. METHODS: We describe six individuals affected by JS as demonstrated by the presence of the typical "molar tooth sign" on MRI. The presence of retinal dystrophy was assessed by fundus examination and electrophysiology by means of full-field electroretinogram (ERG) and visual evoked potentials (VEP) at five spatial frequencies (300-15 min of arc). The macular region was examined with spectral domain optical coherence tomography (SD-OCT). All the exams were performed in awake conditions. All the patients underwent next-generation-sequencing analysis of known JS genes. RESULTS: Pathogenic biallelic variants in either the INPP5E gene or the AHI1 gene were detected in two pairs of siblings, all positive for retinal dystrophy. Genetic testing yielded no results in the remaining two patients, one with bilateral coloboma and retinal dystrophy and the other with normal fundus appearance. Decimal best-corrected visual acuity was between 0.1 and 1.0. In the two pairs of siblings, SD-OCT revealed a posterior staphyloma centred on the fovea, in one case associated with cystoid macular oedema. Macular morphology was just slightly altered in the fifth patient and completely normal in the last patient. Refractive error was between + 2.50 diopter sphere (DS) and - 8 DS and - 4 diopter cylinder ax 45°. ERG waves were markedly lower than the normal limits in both scotopic and photopic components in the two pairs of siblings and in the fifth subject, with VEP P100 latencies and amplitudes delayed and reduced in all spatial frequencies. ERG and VEP were within normal limits in the last patient. CONCLUSIONS: To our knowledge, macular staphyloma has not been described before in JS. Further work is warranted to assess the true prevalence of staphyloma in JS and its connection to retinal dystrophy.

Fluorescein angiography-based diagnosis for retinopathy of prematurity: expert-non expert comparison.

PURPOSE: To evaluate accuracy and inter-rater reliability of RetCam fundus images and digital camera fluorangioscopic images in acute retinopathy of prematurity (ROP) by comparing diagnoses given by trainee ophthalmologists with those provided by expert ophthalmologists. 
 METHODS: This is a multicenter retrospective observational study of diagnostic data from 48 eyes of 24 premature infants with classical ROP, stage II, as evaluated by RetCam 3 and fluorescein angiography (FA). Average gestational age was 25.4 weeks, average weight 804.7 g. A staging grid (with ocular fundus divided into 3 concentric zones) and 24 15° sectors centered around the optic papilla were superimposed on 360° retina photomontages (Photoshop) made from RetCam and FA images. Non expert vs expert diagnosis agreement was measured for each sector by means of Cohen kappa (Fleiss, 1981).
 RESULTS: A high degree of concordance was found. Inter-rater agreement between expert and non expert interpretations of retinal photomontages was greater for fluorangiographic images than for RetCam images, with κ = 0.61-1 for 120/152 (78.9%) sectors examined on the RetCam images and κ = 0.61-1 for 168/198 (84.8%) sectors examined on the FA images.
 CONCLUSIONS: The FA images appear to be easier to interpret than RetCam images, both by expert and non expert ophthalmologists. The results confirm that FA is a good examination technique with a high degree of reliability, even where trainee practitioners are involved. This suggests that retinopathy management can be improved by entrusting diagnostic responsibilities to trainee ophthalmologists, in order to extend access to correct diagnosis, recognition of threshold lesions, and prompt treatment.

Cataracts and Dupuytren disease: a case report and review of the literature.

Purpose. Dupuytren disease is an inherited proliferative and progressive connective disease. Ectopic disease may, however, be located distant from the palmar fascia. 
Methods. Case report and review of the literature. 
Results. We describe a case of symmetric bilateral posterior subcapsular cataracts associated with symmetric bilateral Dupuytren disease and symmetric bilateral Ledderhose disease in a 56-year-old Caucasian man. His medical history was negative for glucocorticoids intake, diabetes, and exposure to radiation. Serum transforming growth factor ß (TGF-ß)1 concentration has been evaluated and was found to be almost double compared to the controls. 
Conclusions. We speculate that the TGF-ß plays an important role for ocular and connective tissue disorders.

Septo-optic dysplasia in childhood: the neurological, cognitive and neuro-ophthalmological perspective.

AIM: We set out to describe 17 patients with septo-optic dysplasia (SOD), focusing on the little-explored neurological, cognitive, and neuro-ophthalmological components. A further aim was to identify possible clinical correlations and phenotypic characteristics within the diagnostic spectrum. METHOD: We collected clinical-instrumental data (from the history, general and neurological examination, developmental assessment, and neuro-ophthalmological, neuroradiological, neurophysiological, and endocrinological evaluations) on nine males and eight females (mean age 34.4mo, SD 31.6; range 4mo-9y 6mo) diagnosed with SOD who were referred to our Centre of Child Neuro-ophthalmology between 1999 and 2010. RESULTS: We observed a heterogeneous clinical spectrum characterized by nervous system, visual, and endocrine dysfunctions; optic nerve involvement was present in all 17 children, midline brain defects in 14, and cortical developmental malformations in seven. Developmental/cognitive delay and relational and communication difficulties were observed in eight and seven children, respectively, and reduced visual acuity and oculomotor dysfunction were observed in all. Pituitary hormone deficiencies were present in nine children. INTERPRETATION: Nervous system involvement emerged as a key feature of SOD. As part of a holistic approach to the disease, particular attention should be paid to this aspect. The emergence of new clinical correlations and correlations between clinical features and three SOD subtypes opens the way for better clarification of this disease and, therefore, more targeted diagnosis, follow-up, and care of affected children.

Neuro-ophthalmological disorders in cerebral palsy: ophthalmological, oculomotor, and visual aspects.

AIM: Cerebral visual impairment (CVI) is a disorder caused by damage to the retrogeniculate visual pathways. Cerebral palsy (CP) and CVI share a common origin: 60 to 70% of children with CP also have CVI. We set out to describe visual dysfunction in children with CP. A further aim was to establish whether different types of CP are associated with different patterns of visual involvement. METHODS: A total of 129 patients (54 females, 75 males; mean age 4 y 6 mo, SD 3 y 5 mo; range 3 mo-15 y) with CP (51 with diplegia, 61 with tetraplegia, and 17 with hemiplegia; 62 [48%] of participants were able to walk) and CVI enrolled at the Centre of Child Neuro-ophthalmology (at the Department of Child Neurology and Psychiatry, IRCCS 'C. Mondino Institute of Neurology', University of Pavia) underwent an assessment protocol including neurological examination, developmental and/or cognitive assessment, neuro-ophthalmological evaluation including ophthalmological assessment, evaluation of visual acuity, contrast sensitivity, optokinetic nystagmus, visual field and stereopsis, and neuroradiological investigations. RESULTS: Visual dysfunction in diplegia was characterized mainly by refractive errors (75% of patients), strabismus (90%), abnormal saccadic movements (86%), and reduced visual acuity (82%). The participants with hemiplegia showed strabismus (71%) and refractive errors (88%); oculomotor involvement was less frequent (59%). This group had the largest percentage of patients with altered visual field (64%). Children with tetraplegia showed a severe neuro-ophthalmological profile, characterized by ocular abnormalities (98%), oculomotor dysfunction (100%), and reduced visual acuity (98%). INTERPRETATION: Neuro-ophthalmological disorders are one of the main symptoms in CP. Each clinical type of CP is associated with a distinct neuro-ophthalmological profile. Early and careful neuro-ophthalmological assessment of children with CP is essential for an accurate diagnosis and for personalized rehabilitation.

Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.

PURPOSE: To identify the molecular basis of Leber's congenital amaurosis (LCA) in a cohort of Italian patients and to perform genotype-phenotype analysis. METHODS: DNA samples from 95 patients with LCA were analyzed by using a microarray chip containing disease-associated sequence variants in eight LCA genes. In addition, all patients in whom no mutations were identified by microarray were subjected to sequence analysis of the CEP290 gene. Patients with mutations identified underwent a detailed ophthalmic evaluation. RESULTS: Disease-causing mutations were identified in 28% of patients, and twelve novel variants were identified. Mutations occurred more frequently in the RPE65 (8.4%), CRB1 (7.4%), and GUCY2D (5.2%) genes. Mutations in CEP290 were found in only 4.2% of the patients analyzed. Clinical assessment of patients carrying RPE65 or CRB1 mutations revealed the presence of retained visual capabilities in the first decade of life. RPE65 mutations were almost always associated with normal macular thickness, as assessed by optical coherence tomography (OCT), whereas CRB1 mutations were associated with reduced retinal thickness and a coarsely laminated retina. Fundus autofluorescence was mostly observed in patients with RPE65 and GUCY2D mutations and was not elicitable in patients carrying CRB1. CONCLUSIONS: RPE65 gene mutations represented a significant cause of LCA in the Italian population, whereas GUCY2D and CEP290 mutations had a lower frequency than that found in other reports. This finding suggests that the genetic epidemiology of LCA in Italy is different from that reported in the United States and in northern European countries. Autofluorescence in patients with RPE65 mutations was more frequently associated with preserved retinal thickness, which suggests that these mutations are not associated with progression of retinal degeneration. Therefore, normal retinal thickness (identified with OCT) and fundus autofluorescence may be the means with which to identify patients with LCA who carry RPE65 mutations, which are expected to be a potential gene therapy target in the near future.