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Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been associated with ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6), the majority of these being implicated in the cone phototransduction cascade. CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors and is one of the major disease-associated genes for ACHM. Herein, we provide a comprehensive overview of the CNGA3 variant spectrum in a cohort of 1060 genetically confirmed ACHM patients, 385 (36.3%) of these carrying "likely disease-causing" variants in CNGA3. Compiling our own genetic data with those reported in the literature and in public databases, we further extend the CNGA3 variant spectrum to a total of 316 variants, 244 of which we interpreted as "likely disease-causing" according to ACMG/AMP criteria. We report 48 novel "likely disease-causing" variants, 24 of which are missense substitutions underlining the predominant role of this mutation class in the CNGA3 variant spectrum. In addition, we provide extensive in silico analyses and summarize reported functional data of previously analyzed missense, nonsense and splicing variants to further advance the pathogenicity assessment of the identified variants.

Significant inter-individual variation in terms of susceptibility to several stress-related disorders, such as myocardial infarction and Alzheimer’s disease, and therapeutic response has been observed among healthy subjects. The molecular features responsible for this phenomenon have not been fully elucidated. Proteomics, in association with bioinformatics analysis, offer a comprehensive description of molecular phenotypes with clear links to human disease pathophysiology. The aim of this study was to conduct a comparative plasma proteomics analysis of glucocorticoid resistant and glucocorticoid sensitive healthy subjects and provide clues of the underlying physiological differences. For this purpose, 101 healthy volunteers were given a very low dose (0.25 mg) of dexamethasone at midnight, and were stratified into the 10% most glucocorticoid sensitive (S) (n = 11) and 10% most glucocorticoid resistant (R) (n = 11) according to the 08:00 h serum cortisol concentrations determined the following morning. One month following the very-low dose dexamethasone suppression test, DNA and plasma samples were collected from the 22 selected individuals. Sequencing analysis did not reveal any genetic defects in the human glucocorticoid receptor (NR3C1) gene. To investigate the proteomic profile of plasma samples, we used Liquid Chromatography-Mass Spectrometry (LC-MS/MS) and found 110 up-regulated and 66 down-regulated proteins in the S compared to the R group. The majority of the up-regulated proteins in the S group were implicated in platelet activation. To predict response to cortisol prior to administration, a random forest classifier was developed by using the proteomics data in order to distinguish S from R individuals. Apolipoprotein A4 (APOA4) and gelsolin (GSN) were the most important variables in the classification, and warrant further investigation. Our results indicate that a proteomics signature may differentiate the S from the R healthy subjects, and may be useful in clinical practice. In addition, it may provide clues of the underlying molecular mechanisms of the chronic stress-related diseases, including myocardial infarction and Alzheimer’s disease.

Purpose: To determine the efficacy of scleral buckling in eyes with stage 4A and 4B retinopathy of prematurity (ROP).Methods: Seven eyes of five premature infants underwent scleral buckling for stage 4 ROP in zone II. Five eyes had stage 4A ROP, and two eyes had stage 4B ROP. Six eyes had previous diode laser photocoagulation, and one eye had received an intravitreal ranibizumab injection. Scleral buckling was the procedure of choice due to lack of access to specialized pediatric vitrectomy instrumentation. Average age at surgery was 3.4 months. Postoperative anatomic retinal status, visual acuity outcome and refractive error were assessed. Results: The scleral buckle was removed on average 8 months after surgery. Retinal reattachment was achieved in all seven eyes. At final follow-up one eye had macular ectopia and disc dragging, one eye had a macular traction fold and two eyes had optic disc pallor. Average myopic error after buckle removal was -7.5 D.Conclusion: Scleral buckling can be performed safely and effectively in 4A and 4B stage ROP in critically-ill infants, when access to specialized pediatric vitrectomy instrumentation is limited. This surgical technique may provide adequate relief of vitreoretinal traction with improved visual potential.

Στόχος της διδακτορικής διατριβής υπήρξε η αναλυτική και λεπτομερής συγκριτική επισκόπηση του άρθρου 72 του ΚΠολΔ και του άρθρου 2900 του Codice Civile και η εξαγωγή χρήσιμων συμπερασμάτων από την ευρύτερη εφαρμογή του θεσμού στο ιταλικό δίκαιο, με αναζήτηση των σημείων εκείνων που η θεωρητική επεξεργασία και η Νομολογιακή εφαρμογή του ιταλικού θεσμού θα μπορούσε να αποτελέσει θετική επιρροή του δικαίου της γειτονικής χώρας στο ημέτερο, με επωφελείς συνέπειες στην πρακτική εφαρμογή του θεσμού στην Ελλάδα- που είναι ομολογουμένως περιορισμένη. Έγινε εκτενής αναζήτηση πιο περιορισμένη στην γαλλική και μεταφράστηκε στην ελληνική γλώσσα το σύνολο των ιταλικών πηγών. Ο θεσμός της πλαγιαστικής αγωγής, θεσμός μεταφυτευθείς τόσο στην ελληνική, όσο και στην ιταλική έννομη τάξη από το γαλλικό δίκαιο, αποσκοπεί στην πληρέστερη προστασία του δανειστή. Στο ιταλικό δίκαιο πρόβλεψη περί «πλαγιαστικής» αγωγής υπάρχει στο άρθρο 2900 του Αστικού Κώδικα.. Βάση και δικαιολογητικός λόγος της θέσπισής της από τον Νομοθέτη είναι η αρχή της περιουσιακής ευθύνης του οφειλέτη, που προβλέπεται στο άρθρο 2740 CC. Κατά κρατούσα γνώμη στη θεωρία και τη Νομολογία, η καθ’ υποκατάσταση αγωγή επιτελεί λειτουργία κυρίως εξασφαλιστική και συντηρητική. Κατά κρατούσα σήμερα γνώμη στην Ιταλική θεωρία και Νομολογία ο ασκών την καθ’ υποκατάσταση αγωγή, είναι από δικονομικής απόψεως δικονομικώς υποκαθιστών. Ο οφειλέτης πρέπει να κλητευθεί στην δίκη όπου ο δανειστής ασκεί τα δικαιώματά αυτού, χωρίς η «προσεπίκληση» αυτή να σημαίνει άσκηση μιας αυτόνομης αγωγής εναντίον του. Οι επιμέρους προϋποθέσεις που πρέπει σωρευτικά να συντρέχουν για την άσκηση της αγωγής είναι η ιδιότητα του δανειστή και η απόδειξη της ύπαρξης μιας αξίωσης περιουσιακού χαρακτήρα κατά του οφειλέτη (δικαιώματα και αγωγές με περιουσιακό χαρακτήρα είναι εκείνα που έχουν ουσία οικονομικά αποτιμήσιμη), να μην πρόκειται για δικαίωμα που από τη φύση του ή δυνάμει διάταξης ικανό να ασκηθεί μόνο από το δικαιούχο του, η αδράνεια του οφειλέτη, ο κίνδυνος επέλευσης ζημίας στα συμφέροντά του δανειστή από την αδράνεια αυτή (παρών και συγκεκριμένος) και ο αιτιώδης σύνδεσμος μεταξύ της αδρανούς συμπεριφοράς του οφειλέτη και του κινδύνου που επίκειται για τα συμφέροντα του δανειστή. Τα αποτελέσματα των πράξεων που πραγματοποιεί καθ’ υποκατάσταση ο δανειστής επέρχονται άμεσα και αποκλειστικά στην περιουσία του οφειλέτη, ενώ η ευθύνη του δανειστή για την παραβίαση του καθήκοντος επιμέλειας δεν είναι δυνατόν να αποκλειστείΟ θεσμός της πλαγιαστικής αγωγής εμφανίζει σοβαρά μειονεκτήματα, κυρίως αναγόμενα στις αναγκαίες δαπάνες και τον απαιτούμενο χρόνο για τις δικαστικές ενέργειες. Παρά την ιστορική καταγωγή του θεσμού της πλαγιαστικής αγωγής από το γαλλικό δίκαιο, ορισμένες πτυχές της καθ΄υποκατάσταση αγωγής του ιταλικού δικαίου, κρίνονται περισσότερο επιτυχημένες στην πράξη και θα μπορούσαν να δώσουν λύσεις στα δυσχερή από θεωρητικής και πρακτικής απόψεως προβλήματα του θεσμού και να συντελέσουν στην πρόσδωση σε αυτόν στοιχείων ευελιξίας και προσαρμοστικότητας στις χιλιάδες εκφάνσεις αξιώσεων και δικαιωμάτων που μπορεί να δημιουργήσει η ιδιωτική αυτονομία.

Introduction: Diabetic macular edema (DME), wet age-related macular degeneration (AMD) and macular edema due to central retinal vein occlusion (CRVO) are leading causes of vision loss, currently managed with anti-vascular endothelial growth factor injections (anti-VEGF). Aim of this study was to calculate QALYs in patients with DME, AMD and CRVO treated with anti-VEGF agents (QALYs+) in a Greek tertiary hospital setting and compare them to theoretical QALYs that the patients would have without treatment (QALYs-). Material and Methods: The study included 143 treatment-naive patients with macular edema due to DM (n=57), AMD (n=79) and CRVO (n=7), who received anti-VEGF injections as monotherapy according to the Treat-and-Extend (T&E) protocol. The anti-VEGF agents were ranibizumab and aflibercept in equivalent fractions. QALYs where calculated by the formula QALY = Utility Value * Time, where “time” refers to the follow-up period of the study. For QALYs-, we assumed that visual acuity remained unchanged during this period.Results: Mean follow-up time was 1+1.3 years in the DME group, 1.3 + 1.2 years in the AMD group and 0.5 +1 years in the CRVO group. For patients with DME, QALYs- were 0.75, and QALYs+ were 0.78 (QALY difference +0.033, p=0.439). For patients with AMD, QALYs- were 0.95 and QALYs+ were also 0.95 (QALY difference 0, p=0.45). QALYs- of patients with CRVO were 0.77, and QALYs+ were 0.80 (QALY difference +0.032, p=0.09).Discussion/Conclusion: QALYs+ were identical to QALYs- in patients with AMD and QALYs+ were minimally higher than QALYs- in patients with DME and CRVO in this specific Greek setting for a time horizon between 0.5 and 1.3 years. Possible explanations are the short time horizon used in this analysis and the inclusion of data from the better-seeing eye (BSE).

Thermal microcautery is a novel minimally invasive intervention for migraine. We present a case series of twenty-one patients who underwent this technique. Nineteen patients reported improvement in migraine management. Of these four patients went on to complete remission and a further eleven patients reported over 50% improvement. In addition, the majority of patients noted reductions in intensity and duration of headache with a better response to medication. The efficacy of thermal microcautery generates a new hypothesis that attempts to explain how a neuromodulation technique may be helpful in the management of migraine.

This prospective study investigates longitudinal changes in retinal structure in patients with achromatopsia (ACHM) using optical coherence tomography (OCT).Seventeen patients (five adults, 12 children) with genetically confirmed CNGA3- or CNGB3-associated ACHM underwent ocular examination and OCT over a follow-up period of between 2 and 9.33 years (mean = 5.7 years). Foveal tomograms were qualitatively graded and were segmented for quantitative analysis: central macular thickness (CMt), outer nuclear layer thickness (ONLt), and size of the foveal hyporeflective zone (vertical HRZ thickness: HRZt and horizontal HRZ width: HRZw) were measured. Data were analyzed using linear mixed regression models. Both age and visit were included into the models, to explore the possibility that the rate of disease progression depends on patient age.Fifteen of 17 patients (88%) showed longitudinal changes in retinal structure over the follow-up period. The most common patterns of progression was development of ellipsoid zone (EZ) disruption and HRZ. There was a significant increase in HRZt (P = 0.01) and HRZw (P = 0.001) between visits and no significant change in CMt and ONLt. Retinal parameters showed no difference in changes by genetic mutation (CNGA3 (n = 11), CNGB3 (n = 6)).This study demonstrates clear longitudinal changes in foveal structure mainly in children, but also in adults with ACHM, over a long follow-up period. The longitudinal foveal changes suggest that treatment at an earlier age should be favored.

AIM: To report the clinical characteristics and diagnostic procedures used in patients with spasm of the near reflex (SNR), in order to present common investigation strategies and diagnostic pitfalls. METHODS: Retrospective case series of twenty-two patients, mainly children, with SNR or accommodation spasm (AS). AS was diagnosed on the basis of blurred vision and a difference of >2 dioptres between manifest and cycloplegic retinoscopy. If esotropia and miosis were present, the patients were diagnosed with SNR. All patients underwent visual acuity testing, orthoptic evaluation, assessment of refraction before and after cycloplegia, and dilated fundoscopy. Additional diagnostic investigations, such as neuroimaging, lumbar puncture (LP), electrophysiology and blood tests, were also recorded. Screen use among children was assessed in hours per day. RESULTS: There were 19 female and 3 male patients (age range 7-33y, median=10y). Seventeen patients had AS and 5 patients had SNR, with episodic blurry vision and headaches being the most common symptoms. Brain neuroimaging was performed in six patients (27%), although only one had a history of brain trauma. Two of those patients underwent visual evoked potentials and three also underwent LP and received intravenous steroid therapy. The majority of patients (90%) reported prolonged daily screen time (>2h/d), and in 55% of cases there were concurrent social problems or psychological triggers. Treatment consisted of careful explanation of the condition, atropine 1% eye drops and full cycloplegic correction by means of bifocal glasses. CONCLUSION: The diagnosis of SNR and AS may be challenging, because symptoms are usually intermittent and nonspecific, and a large number of patients are often subjected to redundant and potentially time-consuming examinations and treatment, that may exaggerate the underlying psychological disorder. Hence, detailed clinical testing and assessment of psychosocial profile is necessary, in order to avoid unnecessary investigations. Neuroimaging should be performed only in selected cases. Finally, due to prolonged screen use SNR and AS may become more frequent in the future.

ObjectiveTo investigate the morphology of the retina and optic nerve (ON) in microcephaly.MethodsThis was a prospective case-control study including 27 patients with microcephaly and 27 healthy controls. All participants underwent ophthalmologic examination and handheld optical coherence tomography (OCT) of the macula and ON head. The thickness of individual retinal layers was quantified at the foveal center and the parafovea (1,000 μm nasal and temporal to the fovea). For the ON head, disc diameter, cup diameter, cup-to-disc ratio, cup depth, horizontal rim diameter, rim area, peripapillary retinal thickness, and retinal nerve fiber layer thickness were measured.ResultsSeventy-eight percent of patients had ophthalmologic abnormalities, mainly nystagmus (56%) and strabismus (52%). OCT abnormalities were found in 85% of patients. OCT revealed disruption of the ellipsoid zone, persistent inner retinal layers, and irregular foveal pits. Parafoveal retinal thickness was significantly reduced in patients with microcephaly compared to controls, nasally (307 ± 44 vs 342 ± 19 μm, p = 0.001) and temporally (279 ± 56 vs 325 ± 16 μm, p < 0.001). There was thinning of the ganglion cell layer and the inner segments of the photoreceptors in microcephaly. Total peripapillary retinal thickness was smaller in patients with microcephaly compared to controls for both temporal (275 vs 318 μm, p < 0.001) and nasal sides (239 vs 268 μm, p = 0.013).ConclusionsRetinal and ON anomalies in microcephaly likely reflect retinal cell reduction and lamination alteration due to impaired neurogenic mitosis. OCT allows diagnosis and quantification of retinal and ON changes in microcephaly even if they are not detected on ophthalmoscopy.

Cerebral venous sinus thrombosis is a relatively rare type of stroke which can be complicated by intracerebral haemorrhage resulting often in poor prognosis. Antiphospholipid syndrome and systemic lupus erythematosus both have been associated with cerebral venous sinus thrombosis. Furthermore, a few cases combining heparin-induced thrombocytopenia with cerebral venous sinus thrombosis have been described in the literature. We present a 57-year-old female patient who was admitted reporting confusion and fever for 4 days. She was immobilized due to a thoracic vertebral fracture and received enoxaparin as a prophylaxis for deep venous thrombosis. A computed tomography scan demonstrated extensive cerebral venous sinus thrombosis and two ipsilateral haemorrhagic infarcts. Moreover, the patient was serum-positive for heparininduced thrombocytopenia antibodies and had persistent fever. A thorough immunological and serological investigation turned out consistent with antiphospholipid syndrome with possible systemic lupus erythematosus. The patient was treated accordingly and was finally discharged one month later, afebrile, with mild neurological deficits.

Purpose The purpose of this study was to prospectively investigate the association between retinopathy of prematurity (ROP) and ocular growth in premature infants during the earliest weeks of life. Methods Premature infants in the national ROP screening program were recruited and examined at 1- or 2-week intervals between 30 and 38 weeks of postmenstrual age. One hundred infants with gestational age (GA) between 24 and 35 weeks (30.04 + 2.13), and birth weight (BW) between 550 and 2060 g (1251.45 + 317.19) were included in the study. At each examination, the presence, stage, and zone of ROP were recorded along with axial length (AL), central corneal thickness (CCT), and weight gain. Biometric parameters were measured by A-scan biometry. Study variables included GA, BW, AL, CCT, weight gain, relative weight (RW), and dif_AL, dif_CCT, and dif_weight, which are the differences between two consecutive recordings of the same infant. Multiple regression analysis models were used to determine the association between the study variables and ROP. Results dif_AL, dif_CCT, and RW were the most appropriate variables to detect the optimal threshold points that discriminate ROP: weekly increase of AL < 0.095 mm, weekly reduction of CCT < 0.5 μm, or weekly weight gain < 7% is associated with ROP development. Conclusions ROP is associated with delayed ocular development, as eyes of premature infants with ROP have shorter axial lengths and thicker corneas than eyes of premature infants without ROP. The association of AL, CCT, and weight gain with ROP could be of value for future development of predictive models for ROP.

The vas deferens and spermatic vessels entering the inguinal canal through the internal inguinal ring is thought to exclude an intra-abdominal testis. We present a case of high bilateral intra-abdominal testes on a 46,XY boy despite the vas deferens and good-sized vessels passing through the deep rings.Data were collected from clinical records, radiology (ultrasound, magnetic resonance imaging [MRI]), and endocrine blood tests.This case underlines the importance of following the pathway of embryological descent of the testis cranially as well as caudally during diagnostic laparoscopy, to avoid missing this rare anatomical variant.

Purpose To determine feasibility of optic nerve head (ONH) imaging and to characterize ONH development in full-term infants without sedation using handheld spectral-domain optical coherence tomography (SD OCT). Design Prospective cross-sectional study. Participants Three hundred fifty-two children aged between 1 day and 13 years. Methods All participants were imaged using handheld SD OCT without sedation during a single scan session. The percentage of successful scans was calculated. Interexaminer reproducibility and differences between right and left eyes were assessed using intraclass correlation coefficients (ICCs). Images were analyzed using ImageJ software. The developmental trajectories over time for ONH parameters were calculated using fractional polynomial modelling. Main Outcome Measures Disc and cup diameter (expressed as distance in micrometers and visual angle in degrees), cup depth, Bruch's membrane opening–minimum rim width (BMO-MRW), retinal thickness, and retinal nerve fiber layer (RNFL; 1700 μm and 6° from the disc center). Results On average, 70% of participants were imaged successfully. Interexaminer reliability was excellent (ICC, >0.89) for diametric and retinal thickness parameters. Right and left eyes were similar for diametric measurements (ICC, >0.79), but more variable for nasal BMO-MRW, RNFL, and retinal thickness. The mean disc and cup diameter increase by 30% and 40%, respectively, between birth and 13 years of age when expressed as a distance measure, but remained constant (at 5°–5.5° and 2°, respectively) when expressed as a visual angle with reference to the eye nodal point. The peripapillary temporal RNFL demonstrated a marked initial decrease of nearly 35% between birth and approximately 18 months of age. This was followed by a slow increase up to 12 years of age when measured at 1700 μm from the disc center, although there was little change when measured at 6° from the disc center. Conclusions We demonstrated feasibility of handheld SD OCT imaging of the ONH in full-term infants and children without anaesthesia or sedation. This is the first in vivo handheld SD OCT study to describe the development of ONH parameters during the critical early years of visual maturation. Our results provide a normative database for use in routine practice and further studies of ONH pathologic features.

A 65-year-old man with a history of hypertension presented with double vision. Examination revealed wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) (figure 1) and nonsymptomatic, pulse-synchronous, pulsatile proptosis of the left eye (video, [links.lww.com/WNL/A389][1]). According to the patient, there was a history of blunt head trauma in childhood and the pulsatile eye was present since then. CT revealed a meningocele into the left orbit due to a bony defect in the orbital roof (figure 2A). CT angiography ruled out a carotid-cavernous fistula. MRI showed an acute infarction at the midline of the midbrain tegmentum, which involved the medial longitudinal fasciculus bilaterally and caused the WEBINO (figure 2B).1 The pulsatile proptosis was attributed to the childhood head injury and due to the orbital roof fracture and associated meningocele pulsation of the brain vessels passed onto the CSF.2 [1]: http://links.lww.com/WNL/A389

Nystagmus is an involuntary rhythmic oscillation of the eyes, which leads to reduced visual acuity due to the excessive motion of images on the retina. Nystagmus can be grouped into infantile nystagmus (IN), which usually appears in the first 3-6 months of life, and acquired nystagmus (AN), which appears later. IN can be idiopathic or associated to albinism, retinal disease, low vision, or visual deprivation in early life, for example due to congenital cataracts, optic nerve hypoplasia, and retinal dystrophies, or it can be part of neurological syndromes and neurologic diseases. It is important to differentiate between infantile and acquired nystagmus. This can be achieved by considering not only the time of onset of the nystagmus, but also the waveform characteristics of the nystagmus. Neurological disease should be suspected when the nystagmus is asymmetrical or unilateral. Electrophysiology, laboratory tests, neurological, and imaging work-up may be necessary, in order to exclude any underlying ocular or systemic pathology in a child with nystagmus. Furthermore, the recent introduction of hand-held spectral domain optical coherence tomography (HH SD-OCT) provides detailed assessment of foveal structure in several pediatric eye conditions associated with nystagmus and it can been used to determine the underlying cause of infantile nystagmus. Additionally, the development of novel methods to record eye movements can help to obtain more detailed information and assist the diagnosis. Recent advances in the field of genetics have identified the FRMD7 gene as the major cause of hereditary X-linked nystagmus, which will possibly guide research towards gene therapy in the future. Treatment options for nystagmus involve pharmacological and surgical interventions. Clinically proven pharmacological treatments for nystagmus, such as gabapentin and memantine, are now beginning to emerge. In cases of obvious head posture, eye muscle surgery can be performed to shift the null zone of the nystagmus into the primary position, and also to alleviate neck problems that can arise due to an abnormal head posture.

A 37-year-old woman presented to the department of otolaryngology with a 15-day history of frontal headache. The patient had been treated for sinusitis with a 10-day course of amoxicillin and clavulanic acid without any improvement. Five days before presentation, a well-defined, fluctuating forehead

Acute retinal necrosis (ARN) is a rare, potentially blinding condition typically affecting immunocompetent individuals. It is defined by the clinical triad of vitreous inflammation, occlusive vasculopathy, and progressive retinal necrosis, usually located in peripheral retina with circumferential extension. Varicella zoster virus (VZV), herpes simplex virus (HSV), Epstein-Barr virus (EBV) and occasionally cytomegalovirus (CMV) are the common causative agents of ARN. Reports of human herpesvirus 6 (HHV6) infection of the central nervous system (CNS) associated with ocular inflammatory disease are extremely rare. We here report the case of a 22-year-old immunocompetent male who presented with acute bilateral ARN and fourth nerve palsy, following HHV6 infection of the CNS and EBV infectious mononucleosis.

Purpose The goal of this work was to (i) determine patterns of progression in glaucomatous visual field loss, (ii) compare the detection rate of progression between locally condensed stimulus arrangements and conventional 6° × 6° grid, and (iii) assess the individual frequency distribution of test locations exhibiting a local event (i.e., an abrupt local deterioration of differential luminance sensitivity (DLS) by more than -10dB between any two examinations). Methods The visual function of 41 glaucomatous eyes of 41 patients (16 females, 25 males, 37 to 75 years old) was examined with automated static perimetry (Tuebingen Computer Campimeter or Octopus 101-Perimeter). Stimuli were added to locally enhance the spatial resolution in suspicious regions of the visual field. The minimum follow-up was four subsequent sessions with a minimum of 2-month (median 6-month) intervals between each session. Progression was identified using a modified pointwise linear regression (PLR) method and a modified Katz criterion. The presence of events was assessed in all progressive visual fields. Results Eleven eyes (27%) showed progression over the study period (median 2.5 years, range 1.3–8.6 years). Six (55%) of these had combined progression in depth and size and five eyes (45%) progressed in depth only. Progression in size conformed always to the nerve fiber course. Seven out of 11 (64%) of the progressive scotomata detected by spatially condensed grids would have been missed by the conventional 6° × 6° grid. At least one event occurred in 64% of all progressive eyes. Five of 11 (46%) progressive eyes showed a cluster of events. Conclusions The most common pattern of progression in glaucomatous visual fields is combined progression in depth and size of an existing scotoma. Applying individually condensed test grids remarkably enhances the detection rate of glaucomatous visual field deterioration (at the expense of an increased examination time) compared to conventional stimulus arrangements.

Purpose: To characterize the time course of normal foveal development in vivo in term infants and young children using handheld spectral-domain optical coherence tomography (HH-SDOCT). Methods: We obtained 534 HH-SDOCT scans from 261 infants, children, and young adults with a mean age of 4.9 years (range, 0-27 years). Each retinal layer was manually segmented in ImageJ and correlated with gestational age (GA) and visual acuity (VA). The developmental trajectories of each retinal layer at the fovea, parafovea, and perifovea were calculated using fractional polynomial modeling. Results: The central macular thickness (CMT) increases logarithmically between birth and 48.6 months GA. The foveal ganglion cell (GCL), inner plexiform, inner nuclear (INL), and outer plexiform layers decrease in thickness exponentially until 18 months GA. Interestingly, the parafoveal and perifoveal GCL and INL thicknesses initially decrease until 17 months GA and then increase in thickness until 65.5 GA. The foveal outer nuclear layer, inner segment, and outer segment of the photoreceptors increase in thickness logarithmically until 32.4, 26.9, and 45.3 months GA, respectively. The parafoveal and perifoveal outer retinal layers increase in thickness more gradually until 146 months GA. The thickness of the outer retinal layers and CMT were strongly correlated with VA, with r = 0.54 (P Conclusions: We have modeled for the first time the complex, nonlinear developmental trajectories for each retinal layer and demonstrate that development continues until adolescence. Our description of normal development will be helpful in diagnosing, monitoring, and understanding pediatric retinal disease.

Background: In the present study, we evaluated the association of platelet reactivity with vascular function in patients after percutaneous coronary intervention receiving clopidogrel treatment. Methods: We enrolled 150 patients with stable CAD receiving clopidogrel regimen (75 mg/d), 1 month after percutaneous coronary intervention. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as an index of arterial wave reflections. High on treatment platelet reactivity (HPR) was evaluated using Verify Now Assay. Verify Now reports its results in P2Y12 reaction units (PRU), and the diagnostic cutoff value is 230 PRU. Patients were evaluated prospectively up to 24 months. The primary end point was a composite of death from cardiovascular causes, nonfatal major cardiovascular events and hospitalization for cardiovascular causes. Results: There was no difference in the basic clinical and demographic characteristics between subjects with HPR and non-HPR. Subjects with high on treatment platelet reactivity and PRU > 230 had significantly increased PWV (8.81 +/- 2.25 m/s vs. 7.69 +/- 1.95 m/s, p = 0.001) and AIx (25.27 +/- 8.67% vs. 20.87 +/- 10.57%, p = 0.04) compared to subjects with PRU

Injury to the primary visual cortex (V1) typically leads to loss of conscious vision in the corresponding, homonymous region of the contralateral visual hemifield (scotoma). Several studies suggest that V1 is highly plastic after injury to the visual pathways, whereas others have called this conclusion into question. We used functional magnetic resonance imaging (fMRI) to measure area V1 population receptive field (pRF) properties in five patients with partial or complete quadrantic visual field loss as a result of partial V1+ or optic radiation lesions. Comparisons were made with healthy controls deprived of visual stimulation in one quadrant [ldquo;artificial scotomardquo; (AS)]. We observed no large-scale changes in spared-V1 topography as the V1/V2 border remained stable, and pRF eccentricity versus cortical-distance plots were similar to those of controls. Interestingly, three observations suggest limited reorganization: (i) the distribution of pRF centers in spared-V1 was shifted slightly toward the scotoma border in 2 of 5 patients compared with AS controls; (ii) pRF size in spared-V1 was slightly increased in patients near the scotoma border; and (iii) pRF size in the contralesional hemisphere was slightly increased compared with AS controls. Importantly, pRF measurements yield information about the functional properties of spared-V1 cortex not provided by standard perimetry mapping. In three patients, spared-V1 pRF maps overlapped significantly with dense regions of the perimetric scotoma, suggesting that pRF analysis may help identify visual field locations amenable to rehabilitation. Conversely, in the remaining two patients, spared-V1 pRF maps failed to cover sighted locations in the perimetric map, indicating the existence of V1-bypassing pathways able to mediate useful vision.

Aim of the present study was to identify efficient compensatory gaze patterns applied by patients with homonymous visual field defects (HVFDs) under virtual reality (VR) conditions in a dynamic collision avoidance task. Thirty patients with HVFDs due to vascular brain lesions and 30 normal subjects performed a collision avoidance task with moving objects at an intersection under two difficulty levels. Based on their performance (i.e. the number of collisions), patients were assigned to either an “adequate” (HVFDA) or “inadequate” (HVFDI) subgroup by the median split method. Eye and head tracking data were available for 14 patients and 19 normal subjects. Saccades, fixations, mean number of gaze shifts, scanpath length and the mean gaze eccentricity, were compared between HVFDA, HVFDI patients and normal subjects. For both difficulty levels, the gaze patterns of HVFDA patients (N = 5) compared to HVFDI patients (N = 9) were characterized by longer saccadic amplitudes towards both the affected and the intact side, larger mean gaze eccentricity, more gaze shifts, longer scanpaths and more fixations on vehicles but fewer fixations on the intersection. Both patient groups displayed more fixations in the affected compared to the intact hemifield. Fixation number, fixation duration, scanpath length, and number of gaze shifts were similar between HVFDA patients and normal subjects. Patients with HVFDs who adapt successfully to their visual deficit, display distinct gaze patterns characterized by increased exploratory eye and head movements, particularly towards moving objects of interest on their blind side. In the context of a dynamic environment, efficient compensation in patients with HVFDs is possible by means of gaze scanning. This strategy allows continuous update of the moving objects’ spatial location and selection of the task-relevant ones, which will be represented in visual working memory.

The aim of the present study was to examine the effect of homonymous visual field defects (HVFDs) on collision avoidance of dynamic obstacles at an intersection under virtual reality (VR) conditions. Overall performance was quantitatively assessed as the number of collisions at a virtual intersection at two difficulty levels. HVFDs were assessed by binocular semi-automated kinetic perimetry within the 90° visual field, stimulus III4e and the area of sparing within the affected hemifield (A-SPAR in deg 2 ) was calculated. The effect of A-SPAR, age, gender, side of brain lesion, time since brain lesion and presence of macular sparing on the number of collisions, as well as performance over time were investigated. Thirty patients (10 female, 20 male, age range: 19–71 years) with HVFDs due to unilateral vascular brain lesions and 30 group-age-matched subjects with normal visual fields were examined. The mean number of collisions was higher for patients and in the more difficult level they experienced more collisions with vehicles approaching from the blind side than the seeing side. Lower A-SPAR and increasing age were associated with decreasing performance. However, in agreement with previous studies, wide variability in performance among patients with identical visual field defects was observed and performance of some patients was similar to that of normal subjects. Both patients and healthy subjects displayed equal improvement of performance over time in the more difficult level. In conclusion, our results suggest that visual-field related parameters per se are inadequate in predicting successful collision avoidance. Individualized approaches which also consider compensatory strategies by means of eye and head movements should be introduced.

Background: Lesions affecting the pretectum or the brachium of the superior colliculus (brachium) and sparing the optic tract cause a contralateral relative afferent pupil defect (RAPD) but no visual field loss. It has been assumed that the pupillomotor pathways within the brachium are a continuation of the pupillomotor pathways traveling in the optic tract. To investigate this assumption, we looked for hemihypokinesia by means of pupil perimetry. Methods: Pupillary hemifield stimulation was performed in a 65-year-old woman with normal visual fields and an isolated left RAPD due to a cerebral hemorrhage affecting the right dorsal midbrain. The pupil responses from light stimulation of the nasal inferior, nasal superior, and temporal inferior and temporal superior quadrants of both eyes were recorded using computerized binocular infrared pupillography. Each stimulus was presented 5 times and the mean amplitude of the pupil response was calculated for each stimulus location. Results: Pupil perimetry demonstrated a marked hemihypokinesia (reduced light reaction) in the hemifield contralateral to the site of the lesion. Conclusions: Our experiment suggests that the brachium is indeed a continuation of the afferent pupillary fibers traveling in the optic tract. (J Neuro-Ophthalmol 2009;29:33–36)

Purpose The aim of this study was to assess whether visual field-related parameters per se are able to predict driving performance of patients with homonymous visual field defects (HVFDs) and healthy controls in a standardized virtual reality (VR) environment. Methods Thirty-two patients with HVFDs due to cerebro-vascular lesions and 32 healthy control subjects underwent testing on a driving simulator under two levels of traffic density. Driving performance was defined as the frequency of accidents under VR-conditions. From the binocular visual field, as measured with kinetic perimetry, we assessed the area of sparing within the affected hemifield (A-SPAR) and the perimetric reaction time (RT). Results Frequency of traffic accidents was best explained by traffic density, age of individuals, A-SPAR and RT. This model explained 78% of the total variability (Radj2 = 0.78). All factors were significant. The effect of traffic density explained 63.4 % of the total variance. Age, A-SPAR and RT were minor effects explaining only 2.7%, 2.0% and 0.9% respectively. Conclusion The extent of the visual field loss is weakly related to driving performance. This finding suggests that – at least for this group of patients – the visual field-related parameters should not be taken as the sole indicator of fitness to drive. Some patients with HVFDs demonstrated sufficient compensatory driving behavior during the simulated test ride, presumably due to eye and head movements. Driving performance declined slightly with age; these changes were exacerbated in the presence of cerebro-vascular disease.

Retinal development normally involves migration of the inner retinal layers away from the fovea, migration of the cone photoreceptors into the fovea, and elongation of the photoreceptors over time. This process is arrested prematurely in albinism. However, because retinal development continues at least until the age of 4 years, when development arrests in albinism is uncertain. In this study we outlined the time course of retinal development in children with albinism.We studied 44 children with a diagnosis of albinism and 223 control participants. All participants were aged between 0 and 6 years. We obtained 219 mixed cross-sectional and longitudinal optical coherence tomography examinations in the albinism group and compared them with 558 control examinations. Retinal layer segmentation was performed with ImageJ software. Generalised linear mixed regression modelling was used to analyse group differences in retinal development.In the albinism group, inner retinal layer migration from the fovea was delayed and arrested prematurely, resulting in a significantly thicker central macular thickness than in the control group (p0·0001). Whereas the central macular thickness increased with age in the control group, in the albinism group it initially decreased with age as a result of continuing regression of the inner retinal layers (p=0·041). The perifoveal retinal thickness was significantly decreased in albinism from a reduction of both inner (p0·0001) and outer (p0·0001) retinal layer thicknesses. There was evidence that the photoreceptor layers across the fovea were elongating in albinism, albeit at a reduced rate, compared with the control group. This difference was most apparent for the foveal photoreceptor inner segment (p=0·001).Our findings show that perturbations exist in several aspects of retinal development including the migration and differentiation of the neuronal cells within the retina. We showed continuing regression of the inner retinal layers and elongation of the photoreceptor layers suggesting residual plasticity of the developing albino retina. This finding is important because treatment at the earliest stages of the condition might normalise retinal development and optimise vision.UK Medical Research Council (grant number MR/J004189/1), Ulverscroft Foundation, National Eye Research Centre, Nystagmus Network UK.

To assess the spatial distribution of glaucomatous visual field defects (VFDs) obtained with regionally condensed stimulus arrangements.Sixty-three eyes of 63 glaucoma subjects were examined with threshold-estimating automated static perimetry (full threshold 4-2-1 dB strategy with at least three reversals) on an automatic campimeter or a full-field perimeter. Stimuli were added by the examiner to regionally enhance spatial resolution in regions that were suspicious for a glaucomatous VFD. These regions were characterized by contiguous local VFDs, attributable to the retinal nerve fiber bundle course according to the impression of the examiner. The added stimulus locations were subsets of a predefined, dense perimetric grid. All VFD locations with P0.05 (total deviation plots) were assessed by superimposing the visual field records of all participants.Glaucomatous VFD loss occurred more frequently in the upper than in the lower hemifield, with a typical retinal nerve fiber-related pattern and a preference of the nasal step region. More than 50% of the eyes with predominantly mild to moderate glaucomatous field loss showed defective locations in the immediate superior paracentral region within an eccentricity of 3°.Conventional thresholding white-on-white perimetry with regionally enhanced spatial resolution reveals that glaucomatous visual field loss affects the immediate paracentral area, especially the upper hemifield, in many eyes with only mild to moderate glaucomatous visual field loss. Detailed knowledge about the spatial pattern and the local frequency distribution of glaucomatous VFDs is an essential prerequisite for creating regionally condensed stimulus arrangements for adequate detection and follow-up of functional glaucomatous damage.

We investigated the task-specific role of eye and head movements as a compensatory strategy in patients with homonymous visual field deficits (HVFDs) and in age-matched normal controls. All participants were tested in two tasks, i.e. a dot counting (DC) task requiring mostly simple visual scanning and a cognitively more demanding comparative visual search (CVS) task. The CVS task involved recognition and memory of geometrical objects and their configuration in two test fields. Based on task performance, patients were assigned to one of two groups, "adequate" (HVFD(A)) and "inadequate" (HVFD(I)); the group definitions based on either task turned out to be identical. With respect to the gaze related parameters in the DC task we obtained results in agreement with previous studies: the gaze pattern of HVFD(A) patients and normal controls did not differ significantly, while HVFD(I) patients showed increased gaze movement activity. In contrast, for the more complex CVS task we identified a deviating pattern of compensatory strategy use. Adequately performing subjects, who had used the same gaze strategies as normals in the DC task, now changed to increased gaze movement activity that allowed coping with the increasing task demands. Inadequately performing patients switched to a novel pattern of compensatory behavior in the CVS task. Different compensatory strategies are discussed with respect to the task-specific demands (in particular working memory involvement), the specific behavioral deficits of the patients, and the corresponding brain lesions.