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.

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.

Anterior Uveitis and Coats Disease in a 16-Year-Old Girl with Noonan Syndrome-A Case Report.

Background: Noonan syndrome (NS) represents a fairly common genetic disorder with a highly variable phenotype. Its features include inherited heart defects, characteristic facial features, short stature, and mild retardation of motor skills. Case presentation: A 16-year-old Caucasian girl with NS reported visual deterioration, photophobia, and pain in the right eye (RE). The initial best-corrected visual acuity (BCVA) was 0.3 in the RE. An examination demonstrated conjunctival and ciliary body hyperemia, keratic precipitates, and flare in the anterior chamber. In addition, post-hemorrhagic floaters, tortuous vessels, and an epiretinal membrane in the RE were present. Diagnosis of unilateral anterior uveitis was made, and this resolved after the use of topical steroids and cycloplegic drops. Due to the presence of retinal telangiectasias and extraocular exudates (consistent with Coats' disease (CD) stage 2A) in the RE, laser therapy was performed. The patient remains under constant follow-up, and after one year, the BCVA in the RE was 0.7. Conclusions: Here, we report the clinical characteristics, genetic findings, and retinal imaging results of a patient with NS. To our knowledge, this is, to date, the first report of an association of NS with a PTPN11 mutation with anterior uveitis and CD.

Isolated retinal astrocytic hamartoma with 7-year follow-up: A case report.

RATIONALE: Retinal astrocytic hamartoma (RAH) is a rare benign tumor originating from astrocytic cells located in the neural cell layer of the retina. It is commonly seen in patients with phakomatoses such as tuberous sclerosis complex or neurofibromatosis, rarely as an isolated retinal mass. This lesion is usually asymptomatic; however, these located in the area of the optic nerve, macula, or exhibiting the features of exudation, neovascularization may present visual disturbances and decreased visual acuity. PATIENT CONCERNS: We present a rare case of a 15-year-old boy, with no significant past medical history, whose cause of visual disturbances turned out to be isolated RAH. DIAGNOSES: Based on the results of color images of the fundus, fluorescein angiography as well as the analysis of magnetic resonance imaging, the patient was diagnosed with RAH. INTERVENTIONS: Additionally an B-scan ultrasonography, static and kinetic perimetry were performed. OUTCOMES: Fundoscopic examination showed a unilateral yellowish, well-circumscribed, mulberry-like lesion with a wide base, located in inferosnasal quadrant, in the vinicity of the optic nerve. The patient underwent neurological, pediatric, and genetic evaluations that excluded other pathological findings or underlying systemic disease. LESSONS: The prognosis for RAH is generally good, however, the lesion requires regular ophthalmologic follow-up to rule out the progression of the tumor mass. The patient 7-year follow-up history is without evidence of tumor growth, local or general deterioration of the condition.

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.

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.

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.