Retinal primary cilia and their dysfunction in retinal neurodegenerative diseases: beyond ciliopathies.

Primary cilia are sensory organelles that extend from the cellular membrane and are found in a wide range of cell types. Cilia possess a plethora of vital components that enable the detection and transmission of several signaling pathways, including Wnt and Shh. In turn, the regulation of ciliogenesis and cilium length is influenced by various factors, including autophagy, organization of the actin cytoskeleton, and signaling inside the cilium. Irregularities in the development, maintenance, and function of this cellular component lead to a range of clinical manifestations known as ciliopathies. The majority of people with ciliopathies have a high prevalence of retinal degeneration. The most common theory is that retinal degeneration is primarily caused by functional and developmental problems within retinal photoreceptors. The contribution of other ciliated retinal cell types to retinal degeneration has not been explored to date. In this review, we examine the occurrence of primary cilia in various retinal cell types and their significance in pathology. Additionally, we explore potential therapeutic approaches targeting ciliopathies. By engaging in this endeavor, we present new ideas that elucidate innovative concepts for the future investigation and treatment of retinal ciliopathies.

Aland Island Eye Disease with Retinoschisis in the Clinical Spectrum of CACNA1F-Associated Retinopathy-A Case Report.

Aland island eye disease (AIED), an incomplete form of X-linked congenital stationary night blindness (CSNB2A), and X-linked cone-rod dystrophy type 3 (CORDX3) display many overlapping clinical findings. They result from mutations in the CACNA1F gene encoding the α1F subunit of the Cav1.4 channel, which plays a key role in neurotransmission from rod and cone photoreceptors to bipolar cells. Case report: A 57-year-old Caucasian man who had suffered since his early childhood from nystagmus, nyctalopia, low visual acuity and high myopia in both eyes (OU) presented to expand the diagnostic process, because similar symptoms had occurred in his 2-month-old grandson. Additionally, the patient was diagnosed with protanomalous color vision deficiency, diffuse thinning, and moderate hypopigmentation of the retina. Optical coherence tomography of the macula revealed retinoschisis in the right eye and foveal hypoplasia in the left eye. Dark-adapted (DA) 3.0 flash full-field electroretinography (ffERG) amplitudes of a-waves were attenuated, and the amplitudes of b-waves were abolished, which resulted in a negative pattern of the ERG. Moreover, the light-adapted 3.0 and 3.0 flicker ffERG as well as the DA 0.01 ffERG were consistent with severely reduced responses OU. Genetic testing revealed a hemizygous form of a stop-gained mutation (c.4051C>T) in exon 35 of the CACNA1F gene. This pathogenic variant has so far been described in combination with a phenotype corresponding to CSNB2A and CORDX3. This report contributes to expanding the knowledge of the clinical spectrum of CACNA1F-related disease. Wide variability and the overlapping clinical manifestations observed within AIED and its allelic disorders may not be explained solely by the consequences of different mutations on proteins. The lack of distinct genotype-phenotype correlations indicates the presence of additional, not yet identified, disease-modifying factors.

First Case Report of Developmental Bilateral Cataract with a Novel Mutation in the ZEB2 Gene Observed in Mowat-Wilson Syndrome.

Background: Mowat-Wilson syndrome (MWS) is extremely rare multisystemic autosomal dominant disorder caused by mutations in the Zinc Finger E-Box Binding Homeobox 2 (ZEB2) gene. Ocular pathologies are one of the symptoms that appear in the clinical picture of MWS individuals, but not many have been described so far. Pathologies such as optic nerve or retinal epithelium atrophy, iris or optic disc coloboma as well as congenital cataracts have been most frequently described until now. Therefore, we would like to report the first case of bilateral developmental cataract in a 9-year-old girl with MWS who underwent successful cataract surgery with intraocular lens implantation. Case Presentation: A 9-year-old girl, diagnosed with p.Gln694Ter mutation in ZEB2 gene and suspicion of MWS was referred to the Children's Outpatient Ophthalmology Clinic for ophthalmological evaluation. Her previous assessments revealed abnormalities of the optic nerve discs. The patient was diagnosed with atrophy of the optic nerves, convergent strabismus, and with-the-rule astigmatism. One year later, during the follow-up visit, the patient was presented with decreased visual acuity (VA), developmental total cataract in the right eye and a developmental partial cataract in the left eye. This resulted in decreased VA confirmed by deteriorated responses in visual evoked potential (VEP) test. The girl underwent a two-stage procedure of cataract removal, first of one eye and then of the other eye with artificial lens implants. In the 2 years following the operation, no complications were observed and, most remarkably, VA improved significantly. Conclusions: The ZEB2 gene is primarily responsible for encoding the Smad interaction protein 1 (SIP1), which is involved in the proper development of various eye components. When mutated, it results in multilevel abnormalities, also in the proper lens formation, that prevent the child from normal vision development. This typically results in the formation of congenital cataracts in children with MWS syndrome, however, our case shows that it also leads to the formation of developmental cataracts. This is presumably due to the effect of the lack of SIP1 on other genes, altering their downstream expression and is a novel insight into the importance of the SIP1 in the occurrence of ocular pathologies. To the best of our knowledge, this is the first case of bilateral developmental cataract in the context of MWS. Moreover, a novel mutation (p.Gln694Ter) in the ZEB2 gene was found corresponding to this syndrome entity. This report allows us to gain a more comprehensive insight into the genetic spectrum and the corresponding phenotypic features in MWS syndrome patients.

CDHR1-Related Cone-Rod Dystrophy: Clinical Characteristics, Imaging Findings, and Genetic Test Results-A Case Report.

Background: Cone-rod dystrophies (CRDs) are a heterogeneous group of inherited retinal diseases (IRDs) characterized by cone photoreceptor loss, that is followed by subsequent rod photoreceptor impairment. Case presentation: A 49-year-old man complaining of diminution of vision in both eyes (OU) was referred to our outpatient clinic. He reported visual loss for 5 years, but it was most progressive during the last few months. The best-corrected visual acuity (BCVA) at presentation was 0.4 in the right eye (RE) and 1.0 in the left eye (LE). Fundus fluorescein angiography (FFA) revealed granular hyperfluorescence in the macula and concomitant areas of capillary atrophy. Flash full-field electroretinography (ffERG) showed lowering of a and b waves as well as prolonged peak time in light-adapted conditions. However, outcomes of dark-adapted ERGs were within normal limits. Based on the constellation of clinical, angiographic, and electrophysiological tests findings, a diagnosis of IRD was suspected. Genetic testing showed a homozygous, pathogenic c.783G>A mutation in the cadherin-related family member 1 (CDHR1) gene, which confirmed CRD type 15 (CRD15). Conclusions: We demonstrate the clinical characteristics, retinal imaging outcomes, and genetic test results of a patient with CRD15. Our case contributes to expanding our knowledge of the clinical involvement of the pathogenic mutation c.783G>A in CDHR1 variants.

Evaluation of Macular Ganglion Cell-Inner Plexiform Layer in Children with Deprivational Amblyopia Who Underwent Unilateral Cataract Surgery.

Background and Objectives: The aim of the study is to assess macular ganglion cell and inner plexiform layer (mGCIPL) thickness in deprivational amblyopic eyes (AE), fellow non-amblyopic eyes (FE) and normal eyes (NE) using spectral. domain optical coherence tomography (SD-OCT). Materials and Methods: Twenty two children (64% boys) who underwent surgical removal of unilateral congenital or developmental cataracts and exhibited visual impairment despite postoperative visual rehabilitation were included in the study. Cataract surgery was performed in patients aged 55.82 ± 35.85 months (range 6 to 114 months). The mean age of the study group was 9.73 ± 2.85 years (range 5 to 15 years). The comparison group consisted of 22 healthy age- and gender-matched children. The best corrected visual acuity (BCVA) after surgery was: 0.75 ± 0.27 (range 0.3 to 1.3) in AE, 0.1 ± 0.13 (range 0 to 0.5) in FE and 0.04 ± 0.07 (range 0 to 0.2) in NE. OCT scans were performed in all patients and subsequently corrected for axial length related magnification errors. Results: The average thickness of mGCIPL was 70.6 ± 11.28 µm in AE; 77.50 ± 6.72 µm in FE and 81.73 ± 5.18 µm in NE. We found that mGCIPL was statistically significantly thinner in deprivation AE compared to FE (p = 0.038) and NE (p = 0.0005). The minimum thickness of mGCIPL was respectively: 62.68 ± 13.2 µm, 70.3 ± 7.61 µm, and 74.5 ± 5.47, and also differed between AE and FE (p = 0.023) and AE and NE (p = 0.0004). Also, measurements in the inferior, inferotemporal, and superotemporal sectors showed thinning of mGCIPL in AE compared to NE. Conclusions: This analysis may suggest that deprivational amblyopia caused by unilateral congenital or developmental cataract in children may be associated with mGCIPL thinning.

Impact of dorzolamide, benzalkonium-preserved dorzolamide and benzalkonium-preserved brinzolamide on selected biomarkers of oxidative stress in the tear film.

BACKGROUND: Long-term use of topical, especially benzalkonium chloride (BAC)-preserved, antiglaucoma medications can cause a negative impact on the ocular surface. The aim of the study was to assess the effect of topical carbonic anhydrase inhibitors (CAIs) on selected oxidative stress biomarkers in the tear film. METHODS: The patients were divided into four sex-matched groups: group C (n = 25) - control group - subjects who did not use topical antiglaucoma medications, group DL (n = 14) - patients using preservative-free dorzolamide, group DL + BAC (n = 16) - patients using topical BAC-preserved dorzolamide, group BL + BAC (n = 17) - patients using BAC-preserved brinzolamide. Subjects in all the study groups have been using the eye drops two times daily for 6-12 months. The oxidative stress biomarkers in the tear film samples were measured: total protein (TP) concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl (-SH) groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response (TAR), and Oxidative Stress Index (OSI). RESULTS: The advanced oxidation protein products content, Total Oxidant Status as well as superoxide dismutase and catalase activities in the group DL + BAC and BL + BAC were higher in comparison with the group C. The total sulfhydryl groups content was lower in the group DL + BAC and BL + BAC when compared to group C. Oxidative Stress Index was higher in the groups DL + BAC and BL + BAC in comparison with the groups DL and C. CONCLUSIONS: Use of topical benzalkonium chloride-preserved carbonic anhydrase inhibitors increases oxidative stress in the tear film.

Success rates of probing for congenital nasolacrimal duct obstruction at various ages.

BACKGROUND: Although nasolacrimal duct probing is the standard treatment for congenital nasolacrimal duct obstruction (CNLDO) among children, the optimal timing of this procedure has been a topic of debate. The aim of the study was to analyze the clinical efficacy of nasolacrimal duct probing among patients with CNLDO symptoms at various ages. METHODS: An 8-year retrospective study involved 2434 patients (3009 eyes), who underwent nasolacrimal duct probing conducted under topical anesthesia in the operating theatre. The study group consisted of 1148 girls (47.2%) and 1286 boys (52.8%) from 2 weeks to 41 months (average age was 8 ± 5.6 months). The participants were divided into nine age groups: 0-2 months, 3-6 months, 7-9 months, 10-12 months, 13-15 months, 16-18 months, 19-21 months, 22-24 months and over 24 months. RESULTS: Bilateral obstruction was present among 575 (23.6%) children and was associated with a higher percentage of unsuccessful procedures compared to patients with unilateral obstruction (16.9% vs 10.2%, p < 0.001 Chi-square test). The success rate of the initial probing was 87.2% for all children and it was shown that it decreased with age. In the above age groups, it was 87.9%; 91.4%; 89.6%; 86%; 76.3%; 71.3%; 70.3%; 70.2%; 65.4%, respectively. CONCLUSIONS: Probing is a safe and effective procedure. However, age at the time of the initial intervention and bilateral surgery constitute significant risk factors for failed probing. Probing between 7 and 9 months appears to be reasonable treatment strategy for children without recurrent infections. Early surgical intervention may be considered for patients with additional signs.

Secretion and signaling activities of lipoprotein-associated hedgehog and non-sterol-modified hedgehog in flies and mammals.

Hedgehog (Hh) proteins control animal development and tissue homeostasis. They activate gene expression by regulating processing, stability, and activation of Gli/Cubitus interruptus (Ci) transcription factors. Hh proteins are secreted and spread through tissue, despite becoming covalently linked to sterol during processing. Multiple mechanisms have been proposed to release Hh proteins in distinct forms; in Drosophila, lipoproteins facilitate long-range Hh mobilization but also contain lipids that repress the pathway. Here, we show that mammalian lipoproteins have conserved roles in Sonic Hedgehog (Shh) release and pathway repression. We demonstrate that lipoprotein-associated forms of Hh and Shh specifically block lipoprotein-mediated pathway inhibition. We also identify a second conserved release form that is not sterol-modified and can be released independently of lipoproteins (Hh-N*/Shh-N*). Lipoprotein-associated Hh/Shh and Hh-N*/Shh-N* have complementary and synergistic functions. In Drosophila wing imaginal discs, lipoprotein-associated Hh increases the amount of full-length Ci, but is insufficient for target gene activation. However, small amounts of non-sterol-modified Hh synergize with lipoprotein-associated Hh to fully activate the pathway and allow target gene expression. The existence of Hh secretion forms with distinct signaling activities suggests a novel mechanism for generating a diversity of Hh responses.

ESSCA results with the baseline series, 2002-2012: p-phenylenediamine.

BACKGROUND: Allergic contact dermatitis caused by p-phenylenediamine (PPD) is common among all age groups and both sexes. Monitoring of prevalence and intensity of sensitization is important. OBJECTIVE: To evaluate contact allergy to PPD in Europe, and to compare reaction intensities in different European regions. METHODS: Data collected by the European Surveillance System on Contact Allergies (ESSCA) network between 2002 and 2012 from 12 European countries were analysed regarding prevalence, grading of positive reactions to PPD, and relevance. RESULTS: A total of 99 926 PPD-positive patients from 63 departments were included for analysis. The overall (2002-2012) prevalence of PPD sensitization in Europe is ∼4%. Stratified for country, the highest overall standardized prevalence was found in Lithuania, and the lowest in Slovenia. The prevalence of PPD sensitization did not decline over the years. In the southern European countries, higher numbers of strong and extremely strong reactions were registered. The clinical relevance of PPD sensitization varied from half to three-quarters. CONCLUSION: The prevalence of PPD sensitization has not changed over time. Strong and extremely strong patch test reactions are seen more often in the South, probably because of the higher number of PPD-containing hair dye products.

Patch test results of the European baseline series among patients with occupational contact dermatitis across Europe - analyses of the European Surveillance System on Contact Allergy network, 2002-2010.

BACKGROUND: Occupational contact dermatitis is one of the most common occupational diseases in Europe. In order to develop effective preventive measures, detailed and up-to-date data on the incidence, main causes and professions at risk of occupational contact dermatitis are needed. OBJECTIVES: To describe the pattern of patch test reactivity to allergens in the European baseline series of patients with occupational contact dermatitis in different occupations. METHODS: We analysed data collected by the European Surveillance System on Contact Allergy (ESSCA) network from 2002 to 2010, from 11 European countries. RESULTS: Allergens in the European baseline series associated with an at least doubled risk of occupational contact dermatitis include: thiuram rubber chemical accelerators, epoxy resin, and the antimicrobials methylchloroisothiazolinone/methylisothiazolinone, methyldibromo glutaronitrile, and formaldehyde. The highest risk of occupational contact dermatitis was found in occupations classified as 'other personal services workers', which includes hairdressers, nursing and other healthcare professionals, precision workers in metal and related materials, and blacksmiths, tool-makers and related trades workers. CONCLUSIONS: In the planning and implementation of measures aimed at preventing occupational contact dermatitis, the focus should be on the identified high-risk occupational groups and the most common occupational allergies.

ESSCA results with the baseline series, 2009-2012: rubber allergens.

BACKGROUND: Allergic contact dermatitis caused by rubber allergens is common, and causes significant patient morbidity. Contemporary data are important to allow appropriate preventive measures and identification of contact allergy trends. OBJECTIVES: To describe the pattern of patch test reactivity to rubber allergens, including those in the European baseline series. METHODS: Data collected by the European Surveillance System on Contact Allergies (ESSCA) network between 2009 and 2012 from 12 European countries were analysed. RESULTS: Contact allergy to thiuram mix declined over the studied time period, with an overall prevalence of 1.87%. The prevalence of allergy to carba mix was 2.29%, and was significantly increasing. Prevalence rates of sensitization to other rubber allergens were largely unchanged. Statistical analysis with the MOAHLFA index confirmed the strong links between rubber allergy and occupational hand dermatitis. CONCLUSIONS: Changing patterns of allergy to rubber additives have been identified. Inclusion of carba mix in the European baseline series may be appropriate.

[Preservatives as important etiologic factors of allergic contact dermatitis]. / Konserwanty jako istotne czynniki etiologiczne alergicznego kontaktowego zapalenia skóry.

BACKGROUND: Preservatives present in cosmetics and other industrial products can cause allergic contact dermatitis. The aim of the study was to assess the frequency of allergy to selected preservatives in consecutive patients examined due to contact dermatitis in the Nofer Institute of Occupational Medicine, Lódz, and to establish whether individuals sensitized to formaldehyde react simultaneously to formaldehyde releasers. MATERIAL AND METHODS: A group of 405 patients (308 females and 97 males) was examined in 2011-2013. In all participants patch tests with a series of 13 preservatives (paraben mix, formaldehyde, Quaternium 15, chloromethylisothiazolinone/methylisothiazolinone mix, methyldibromoglutaronitrile, diazolidinyl urea, imidazolidinyl urea, DMDM hydantoin, 2-bromo-2-nitropropane-1,3-diol, iodopropynyl butylcarbamate, benzalkonium chloride, sodium metabisulfite, produced by Chemotechnique Diagnostics, Sweden) were performed. RESULTS: Of the 405 patients 74 (including 52 females) showed positive results of patch tests. Contact allergy to at least 1 preservative was noted in 47 (11.6%) patients, including 34 (11%) females and 13 (13.4%) males. Methylisothiazolinone proved to be the most frequent sensitizer--4.7% (5.2% females, 3.1% males) while parabens, 2-bromo-2-nitropropane-1,3-diol and imidazolidinyl urea (0.2%) were found to be the least frequent. Fourteen (3.4%) participants, 10 women and 4 men, were allergic to formaldehyde and/or formaldehyde releasers. In 11 (78.6%) of them monovalent hypersensitivity was observed. In 13 (3.2% of the examined group) patients allergy to preservatives might have been of occupational origin. CONCLUSIONS: Preservatives, particularly isothiazolinones, are significant causal factors of allergic contact dermatitis, including occupational cases. Individuals sensitized to formaldehyde may react simultaneously to formaldehyde releasers, however, such reactions are relatively rare.

Nuclear MMP-9 role in the regulation of rat skeletal myoblasts proliferation.

BACKGROUND INFORMATION: Matrix metalloproteinases (MMPs) are the key enzymes responsible for the remodelling of extracellular matrix. Two of them, namely MMP-2 and MMP-9 (gelatinases A and B, respectively), are expressed in skeletal muscles and are involved in their regeneration after the injury. Although MMPs are primarily known to act extracellularly, recent studies have shown that some of them are also found within the cell. In this study, we examine intracellular localisation of gelatinases during myoblasts differentiation in vitro, focussing the impact of MMPs inhibition on the myoblasts proliferation and function. RESULTS: We show that MMP-9 localises within the S-phase nuclei of in vitro differentiating myoblasts. The inhibition of MMPs activity achieved by either doxycycline (a non-competitive inhibitor of collagenases), TIMP-1 (tissue inhibitor of metalloproteinases 1) or neutralising anti-MMP-9 antibody affects nuclear localisation of this gelatinase, and impacts at myoblasts proliferation. CONCLUSIONS: During myoblasts differentiation, MMP-9 that is localised in nuclei might be involved in the processes regulating cell cycle progression.

[Isothiazolinones as causal factors of contact allergy epidemics in the 20th and 21st centuries]. / Izotiazolinony jako przyczyna epidemii alergii kontaktowej XX i XXI wieku.

Chloromethylisothiazolinone (MCI) and methylisothiazolinone (MI) have been widely used as preservatives in cosmetics, household products and industrial products since the late 1970s. First cases of contact allergy to the MCI/MI combination were noted in 1980-1982 in Sweden. Then, a significant increase in the frequency of sensitization to these compounds was observed in many European centers. The increase has been stopped by the introduction of legislation on their maximum concentrations in consumer and industrial products in Europe and in some non-European countries. But approval of the use of MI alone without limits in industrial products (from 2000) and at a maximum concentration of 100 ppm in cosmetics (from 2005) resulted in an unprecedented increase in the number of individuals sensitized to this compound. Allergic contact dermatitis due to MI occurs in both adults and children. It is often manifested by severe symptoms, which may be also induced by airborne exposure. The most important sources of sensitization include cosmetic products and paints. To counteract the increasing problem of contact allergy epidemic to MI, the recommendations have been developed, suggesting the ban on the use of MI in "leave-on" cosmetics and maximum concentration of 15 ppm in "rinse-off" products. The recommendations are likely to be implemented in 2014.

Lipoproteins and Hedgehog signalling--possible implications for the adrenal gland function.

BACKGROUND: Metabolic syndrome is a common metabolic disorder that is associated with an increased risk of type 2 diabetes and cardiovascular diseases. Disturbances in adrenal steroid hormone production significantly contribute to the development of this disorder. Therefore, it is extremely important to fully understand the mechanisms governing adrenal gland function, both in physiological and pathological conditions. RESULTS: Recently, Sonic hedgehog has emerged as an important regulator of adrenal development, with a possible role in adult gland homeostasis. Recent work of our group shows that lipoproteins are important regulators of Hedgehog signaling; they act as carriers for the spread of Hedgehog proteins, but also contain lipid(s) that inhibit the pathway. CONCLUSIONS: We propose that lipoproteins may affect Sonic hedgehog signaling in the adult adrenal gland at multiple levels. Understanding the interplay between lipoprotein metabolism and adrenal Hedgehog signaling may improve our understanding of how adrenal gland disorders contribute to the metabolic syndrome.

[Manicurists and pedicurists - occupation group at high risk of work-related dermatoses]. / Manikiurzystki i pedikiurzystki jako grupa zawodowa o istotnym ryzyku dermatoz zwiazanych z prac.

In recent years occupational skin and respiratory diseases have been more and more frequently diagnosed in small production and service enterprises. The awareness of occupational exposure and its possible health effects among their workers and employers is not sufficient. Beauty salons, in addition to hairdressers and beauticians, frequently employ manicurists and pedicurists. The workers often happen to perform various activities interchangeably. the health status of beauty salons workers has rarely been assessed. The most numerous reports concern hairdressers. In this occupational group, the occurrence of skin lesions induced by wet work and frequent allergy to metals, hair dyes and bleaches and perm solutions has been emphasized, while information about health hazards for being a manicurist or pedicurist in beauty salons is seldom reported. The aim of this paper is to present professional activities (manicure and pedicure, methods of nail stylization), occupational exposure and literature data on work-related adverse health effects in manicurists and pedicurists. Wet work and exposure to solvents, fragrances, resins, metals, gum, detergents may cause skin disorders (contact dermatitis, urticaria, angioedema, photodermatoses), conjunctivitis, anaphylaxis, respiratory tract diseases, including asthma. The discussed occupations are also associated with the increased incidence of bacterial (particularly purulent), viral and fungal infections and cancer.

Analysis of Peripapillary Retinal Nerve Fiber Layer Thickness in Acute Anterior Uveitis among Children with HLA-B27-Positive Juvenile Idiopathic Arthritis.

PURPOSE: The aim of this study was to evaluate changes in the thickness of the peripapillary retinal nerve fiber layer (pRNFL) in children with a diagnosis of juvenile idiopathic arthritis (JIA) who were positive for human leukocyte antigen (HLA)-B27, treated for the first episode of unilateral acute anterior uveitis (AAU). MATERIALS AND METHODS: This retrospective study included 41 children (aged 5 to 14 years; mean age 8.32 ± 2.4 years) with HLA-B27 positivity and unilateral JIA-AAU, and 40 healthy children. Optical coherence tomography (OCT) imaging was performed during active inflammation and subsequent noninflammatory phases (6 months after the resolution of inflammatory symptoms in the anterior segment of the eye). RESULTS: There was a marked difference in mean pRNFL thickness between eyes with AU in the active phase, unaffected fellow eyes and the control group (110.22 ± 5.95 µm, 102.39 ± 4.39 µm and 95.83 ± 8.84 µm, respectively; p < 0.001). The thickness of pRNFL in eyes with AU in the active phase in all sectors was greater compared to unaffected fellow eyes (p < 0.001) and normal eyes (p < 0.001). In addition, it was demonstrated that pRNFL thickness was significantly increased in the superior and temporal sectors in the unaffected fellow eyes compared to the control group (128.73 ± 13.16 µm vs. 121.48 ± 13.35 µm and 71.37 ± 4.02 µm vs. 64.98 ± 9.12 µm, respectively). Even during the inactive phase, eyes with AU, compared to the healthy control group, had significantly greater pRNFL thickness in the inferior sector (129.78 ± 11.98 µm vs. 122.3 ± 14.59 µm; p = 0.018), along with the temporal sector (70.88 ± 5.48 µm vs. 64.98 ± 9.12 µm; p = 0.001). CONCLUSIONS: An increase in pRNFL thickness in children with unilateral JIA-AAU who were positive for HLA-B27 antigen can be observed in both eyes compared to healthy controls, and this change may persist even after the inflammatory symptoms have resolved. Measurements of pRNFL thickness resulting from JIA-AU-associated glaucoma should be performed during quiescent periods to avoid subclinical changes in pRNFL thickness caused by inflammation. However, when reviewing the results, it should be noted that changes in pRNFL parameters may be present despite evidence of a resolution of inflammation.

Aicardi-Goutières Syndrome with Congenital Glaucoma Caused by Novel TREX1 Mutation.

BACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare genetic disorder characterized by microcephaly, white matter lesions, numerous intracranial calcifications, chilblain skin lesions and high levels of interferon-α (IFN-α) in the cerebrospinal fluid (CSF). However, ocular involvement is reported significantly less frequently. CASE PRESENTATION: We present a case of a neonate with hypotrophy, microcephaly, frostbite-like skin lesions, thrombocytopenia, elevated liver enzymes and hepatosplenomegaly. Magnetic resonance imaging (MRI) of the brain showed multiple foci of calcification, white matter changes, cerebral atrophy, and atrophic dilatation of the ventricular system. The inflammatory parameters were not elevated, and the infectious etiology was excluded. Instead, elevated levels of IFN-α in the serum were detected. Based on the related clinical symptoms, imaging and test findings, the diagnosis of AGS was suspected. Genetic testing revealed two pathogenic mutations, c.490C>T and c.222del (novel mutation), in the three prime repair exonuclease 1 (TREX1) gene, confirming AGS type 1 (AGS1). An ophthalmologic examination of the child at 10 months of age revealed an impaired pupillary response to light, a corneal haze with Haab lines in the right eye (RE), pale optic nerve discs and neuropathy in both eyes (OU). The intraocular pressure (IOP) was 51 mmHg in the RE and 49 in the left eye (LE). The flash visual evoked potential (FVEP) showed prolonged P2 latencies of up to 125% in the LE and reduced amplitudes of up to approximately 10% OU. This girl was diagnosed with congenital glaucoma, and it was managed with a trabeculectomy with a basal iridectomy of OU, resulting in a reduction and stabilization in the IOP to 12 mmHg in the RE and 10 mmHg in the LE without any hypotensive eyedrops. CONCLUSIONS: We present the clinical characteristics, electrophysiological and imaging findings, as well as the genetic test results of a patient with AGS1. Our case contributes to the extended ophthalmic involvement of the pathogenic c.490C>T and c.222del mutations in TREX1.