[Epithelial basement membrane corneal dystrophy: A case report]. / Distrofia de membrana basal epitelial corneal: a propósito de un caso.

Epithelial basement membrane corneal dystrophy is a rare entity, characterized by recurrent corneal erosions secondary to a disorder in the attachment of the corneal epithelium to the basement membrane. To date, mainly the ophthalmological aspect of cases has been reported, with little emphasis on the pathology of this lesion. Here we aim to describe the microscopy and discuss the clinical and therapeutic aspects of a case.

Dual corneal involvement by endothelial and epithelial corneal dystrophies in Steinert's disease: A case of triple dystrophy.

INTRODUCTION: A case of dual corneal involvement due to Fuchs endothelial corneal dystrophy and epithelial basement membrane corneal dystrophy in a patient with Steinert's myotonic dystrophy type 1 is described, and a literature review on the triple association is made. CASE DESCRIPTION: A 52-year-old male diagnosed with myotonic dystrophy type 1 presented due to progressive bilateral vision loss during the past year. A full ophthalmological evaluation was made, with biomicroscopy, funduscopy, anterior segment optical coherence tomography, and endothelial cell count using specular microscopy. Exploration revealed bilateral superior palpebral ptosis, visual acuity 0.5 in the right eye and 0.3 in the left eye, and with an intraocular pressure of 11 and 10 mmHg, respectively. Biomicroscopy revealed map-dot-fingerprint lesions characteristic of epithelial basement membrane corneal dystrophy in both eyes, as well as abundant endothelial guttae due to Fuchs endothelial corneal dystrophy (stage II) and bilateral nuclear and posterior subcapsular cataracts. Specular microscopy in turn showed cell loss and a destructured endothelial map. Finally, anterior segment optical coherence tomography revealed the accumulation of epithelial basement membrane and hyperreflective endothelial excrescences corresponding to guttae. CONCLUSION: The association of Fuchs endothelial corneal dystrophy with myotonic dystrophy has been described and explained by a common genetic basis in the expansion of a CTG trinucleotide repeat, though this is the first reported case of the triple association of Fuchs endothelial corneal dystrophy, epithelial basement membrane corneal dystrophy, and myotonic dystrophy type 1. New mutations or still unknown genetic alterations could possibly explain the triple association reported in our case.

Teaching Video NeuroImages: Posterior Cortical Atrophy Presenting With Balint Syndrome.

We present the case of a 68-year-old woman who developed progressive visuospatial deficits in a period of 18 months, leading to the loss of her independence for activities of daily living. After examination, she showed signs of Balint syndrome with optic ataxia, oculomotor apraxia, and simultanagnosia without visual acuity impairment. After brain imaging showing severe bilateral parieto-occipital association cortex atrophy, a diagnosis of posterior cortical atrophy was made according to the 2017 International Consortium's criteria.

Assessment of corneal epithelial thickness mapping in epithelial basement membrane dystrophy.

PURPOSE: To investigate the corneal epithelial thickness topography with optical coherence tomography (OCT) and its relationship with vision quality in epithelial basement membrane dystrophy (EBMD). METHODS: 45 eyes of EBMD patients, 26 eyes of dry eye (DED) patients and 22 eyes of normal subjects were enrolled. All participants were subjected to 9-mm corneal epithelial mapping with OCT and vision quality was assessed with the optical quality analysis system using the objective scatter index (OSI). Central, superior, inferior, minimum, maximum, and standard deviation of epithelium thickness (Irregularity), were analysed and correlations with the OSI were calculated. RESULTS: The mean (±SD) central, inferior and maximum epithelial thicknesses of the EBMD patients (respectively, 56.4 (±8.1) µm, 58.9 (±6.4) µm, and 67.1 (±8.3) µm) were thicker compared to DED patients (P<0.05) and normal subjects (P<0.05). We found greater irregularity of epithelial thickness in EBMD (5.1±2.5 µm) compared to DED patients (2.6±1.0 µm) (P = 4.4.10-6) and normal subjects (2.1±0.7 µm) (P = 7.6.10-7). The mean OSI was worse in EBMD patients than in DED patients (P = 0.01) and compared to normal subjects (P = 0.02). The OSI correlated with the epithelial thickness irregularity (Spearman coefficient = 0.54; P = 2.65.10-5). CONCLUSIONS: The OCT pachymetry map demonstrated that EBMD patients had thicker corneal epithelium in the central and inferior region. These changes were correlated with objective measurements of vision quality. This OCT characterisation of the EMBD provides a better understanding of the epithelial behaviour in this dystrophy and its role in vision quality.

Asymmetric Bálint's syndrome with multimodal agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading due to subcortical hemorrhage in the left parieto-occipito-temporal area.

We report a patient with asymmetric Bálint's syndrome (predominantly right-sided oculomotor apraxia and simultanagnosia and optic ataxia for the right hemispace), and multimodal agnosia (apperceptive visual agnosia and bilateral associative tactile agnosia) with accompanying right hemianopia, bilateral agraphesthesia, hemispatial neglect, global alexia with unavailable kinesthetic reading, and lexical agraphia for kanji (Japanese morphograms), after hemorrhage in the left parieto-occipito-temporal area. The coexistence of tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading suggests that tactile-kinesthetic information can be interrupted because of damage to the fiber connection from the parietal lobe to the occipito-temporal area, leading to these tactually related cognitive impairments.

Cogan's Syndrome: Clinical Presentations and Update on Treatment.

PURPOSE OF REVIEW: Cogan's syndrome (CS) is a rare systemic vasculitis that can severely affect vision and hearing, which may also have significant systemic effects. Early recognition of this autoimmune disorder and intervention can minimize disabling and irreversible damage. RECENT FINDINGS: This article will review the varying clinical presentations of CS and emerging information of systemic disease associated with CS. We will also review recently published promising treatment outcomes using immune modulating medications. As our framework for recognizing the markers of CS and the associated systemic disorders expands, more effective guidelines and treatment options may emerge.

Efficacy of a Topical Heparan Sulfate Mimetic Polymer on Ocular Surface Discomfort in Patients with Cogan's Epithelial Basement Membrane Dystrophy.

Purpose: Treatment of persistent ocular discomfort in patients with Cogan's epithelial basement membrane dystrophy (EBMD) is a challenge for ophthalmologists. This study aimed to determine the efficacy of a topical heparan sulfate mimetic polymer (HSMP) in reducing ocular discomfort in EBMD patients. Methods: This retrospective, noninterventional study included 22 consecutive patients in 3 tertiary ophthalmological units with spontaneous, recurrent, acute ocular pain, resistant to various topical lubricants. After EBMD diagnosis, HSMP treatment was initiated while lubricating eye drops were continued. The main study outcome was the change in ocular discomfort assessed using the ocular surface disease index (OSDI) from initiation of treatment to last follow-up visit. Results: The mean OSDI decreased from 46.7 ± 22.3 to 31.6 ± 17.4 (P < 0.001) at first visit and 32.5 ± 17.9 (P < 0.01) at last visit. The rate of patients with severe ocular surface disease (OSDI >33) decreased from 68.2% to 36.4% at first visit and 42.9% at last visit. After a median follow-up of 8.5 months, 7 (31.8%) patients discontinued the HSMP treatment due to a marked improvement in ocular surface comfort and no recurrence of ocular pain, 5 (22.7%) due to lack of efficacy, and 1 (4.5%) due to an ocular adverse event (not treatment related). Eight patients continued treatment after the last visit and 1 patient was lost to follow-up. Globally, HSMP prevented acute painful episodes in 11 (61.1%) of 18 patients followed for ∼4 months. Conclusions: Topical HSMP may be an option for alleviating ocular discomfort in patients with EBMD resistant to standard symptomatic treatments.

Histopathology of the Human Inner Ear in the Cogan Syndrome with Cochlear Implantation.

The Cogan syndrome is a rare disorder characterized by nonsyphilitic interstitial keratitis and audiovestibular symptoms. Profound sensorineural hearing loss has been reported in approximately half of the patients with the Cogan syndrome resulting in candidacy for cochlear implantation in some patients. The current study is the first histopathologic report on the temporal bones of a patient with the Cogan syndrome who during life underwent bilateral cochlear implantation. Preoperative MRI revealed tissue with high density in the basal turns of both cochleae and both vestibular systems consistent with fibrous tissue due to labyrinthitis. Histopathology demonstrated fibrous tissue and new bone formation within the cochlea and vestibular apparatus, worse on the right. Severe degeneration of the vestibular end organs and new bone formation in the labyrinth were seen more on the right than on the left. Although severe bilateral degeneration of the spiral ganglion neurons was seen, especially on the right, the postoperative word discrimination score was between 50 and 60% bilaterally. Impedance measures were generally higher in the right ear, possibly related to more fibrous tissue and new bone found in the scala tympani on the right side.

PNKP Mutations Identified by Whole-Exome Sequencing in a Norwegian Patient with Sporadic Ataxia and Edema.

We identified PNKP mutations in a Norwegian woman with AOA. This patient had the typical findings with cognitive dysfunction, peripheral neuropathy, cerebellar dysarthria, horizontal nystagmus, oculomotor apraxia, and severe truncal and appendicular ataxia. In addition, she had hypoalbuminemia and massive lower limb edema which showed some improvement with treatment. Exome sequencing identified two heterozygous mutations, one in exon 14 (c.1196T>C, p.Leu399Pro) and one in exon 16 (c.1393_1396del, p.Glu465*). This is the first non-Portuguese patient with AOA due to PNKP mutations and provides independent verification that PNKP mutations cause AOA.

Nosological delineation of congenital ocular motor apraxia type Cogan: an observational study.

BACKGROUND: The nosological assignment of congenital ocular motor apraxia type Cogan (COMA) is still controversial. While regarded as a distinct entity by some authorities including the Online Mendelian Inheritance in Man catalog of genetic disorders, others consider COMA merely a clinical symptom. METHODS: We performed a retrospective multicenter data collection study with re-evaluation of clinical and neuroimaging data of 21 previously unreported patients (8 female, 13 male, ages ranging from 2 to 24 years) diagnosed as having COMA. RESULTS: Ocular motor apraxia (OMA) was recognized during the first year of life and confined to horizontal pursuit in all patients. OMA attenuated over the years in most cases, regressed completely in two siblings, and persisted unimproved in one individual. Accompanying clinical features included early onset ataxia in most patients and cognitive impairment with learning disability (n = 6) or intellectual disability (n = 4). Re-evaluation of MRI data sets revealed a hitherto unrecognized molar tooth sign diagnostic for Joubert syndrome in 11 patients, neuroimaging features of Poretti-Boltshauser syndrome in one case and cerebral malformation suspicious of a tubulinopathy in another subject. In the remainder, MRI showed vermian hypo-/dysplasia in 4 and no abnormalities in another 4 patients. There was a strong trend to more severe cognitive impairment in patients with Joubert syndrome compared to those with inconclusive MRI, but otherwise no significant difference in clinical phenotypes between these two groups. CONCLUSIONS: Systematical renewed analysis of neuroimaging data resulted in a diagnostic reappraisal in the majority of patients with early-onset OMA in the cohort reported here. This finding poses a further challenge to the notion of COMA constituting a separate entity and underlines the need for an expert assessment of neuroimaging in children with COMA, especially if they show cognitive impairment.

Histopathology of the Inner Ear in a Case With Recent Onset of Cogan's Syndrome: Evidence for Vasculitis.

The association of sensorineural hearing loss and vertigo with inflammatory eye disease, usually interstitial keratitis, has been called Cogan's syndrome. The pathogenesis of Cogan's syndrome is unknown, but it has been assumed to be an immune mediated disorder with vasculitis. The histopathology of the inner ear in Cogan's syndrome has been described in 6 case reports. Although common pathologic findings in these reports include degeneration of the auditory and vestibular neuroepithelium, endolymphatic hydrops, fibrosis, and new bone formation, direct pathologic evidence of a vasculitis has not been published. A possible reason for this failure to identify vasculitis was a substantial delay (range, 4-40 years) between the onset of symptoms and examination of the otopathology. In the current case report, the patient had both auditory and vestibular symptoms and interstitial keratitis with a time delay of only 2 to 4 weeks between symptoms and death. Evidence of a vasculitis as a possible underlying etiology included H&E histopathology and anti-CD45 immunostaining of vessels both in the auditory and vestibular systems, supporting the hypothesis of a vasculitis as a mechanism in this disorder.

Ataxia with oculomotor apraxia type 2 fibroblasts exhibit increased susceptibility to oxidative DNA damage.

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive cerebellar ataxia associated with mutations in SETX, which encodes the senataxin protein, a DNA/RNA helicase. We describe the clinical phenotype and molecular characterization of a Colombian AOA2 patient who is compound heterozygous for a c.994 C>T (p.R332W) missense mutation in exon 7 and a c.6848_6851delCAGA (p.T2283KfsX32) frameshift deletion in SETX exon 21. Immunocytochemistry of patient-derived fibroblasts revealed a normal cellular distribution of the senataxin protein, suggesting that these mutations do not lead to loss or mis-localization of the protein, but rather that aberrant function of senataxin underlies the disease pathogenesis. Furthermore, we used the alkaline comet assay to demonstrate that patient-derived fibroblast cells exhibit an increased susceptibility to oxidative DNA damage. This assay provides a novel and additional means to establish pathogenicity of SETX mutations.

Atypical Cogan's syndrome presenting as bilateral endogenous endophthalmitis.

We report a case of atypical Cogan's syndrome presenting as bilateral endogenous endophthalmitis in a woman with ovarian cancer. A 62-year-old woman with ovarian cancer developed bilateral interstitial keratitis and panuveitis accompanied by bilateral sensorineural hearing loss and chondritis. Auricular cartilage biopsy ruled out relapsing polychondritis and the diagnosis of atypical Cogan's syndrome was set clinically.

Corneal nerve architecture in a donor with unilateral epithelial basement membrane dystrophy.

BACKGROUND: Epithelial basement membrane dystrophy (EBMD) is by far the most common corneal dystrophy. In this study, we used a newly developed method of immunofluorescence staining and imaging to study the entire corneal nerve architecture of a donor with unilateral EBMD. METHOD: Two fresh eyes from a 56-year-old male donor were obtained; the right eye of the donor was diagnosed with EBMD and the left was normal. After slit lamp examination, the corneas were immunostained with anti-ß-tubulin III antibody. Images were recorded by a fluorescent microscope equipped with a Photometrics digital camera using MetaVue imaging software. RESULTS: The left cornea appeared normal as observed by slit lamp and stereomicroscope, but the right eye had numerous irregular geographic patches in the basement membrane. Immunofluorescence showed no difference in the stromal nerve distribution between the 2 eyes, but there were areas without innervations in the EBMD cornea. Subbasal nerve fibers also showed tortuous courses and fewer divisions. There was a significant decrease in the density of subbasal nerve fibers and the number of terminals in the right eye. CONCLUSION: We show for the first time detailed nerve architecture in an EBMD cornea. Our results suggest that EBMD-induced abnormalities of basement membrane altered epithelial nerve architecture and decreased nerve density, contributing to the pathology of the disease.

[Vascular involvement in Cogan's syndrome. A case report]. / Atteinte vasculaire et syndrome de Cogan. Une observation.

Vascular manifestations of Cogan's syndrome are rarely reported. We report the case of a young woman followed for typical Cogan's disease. Serious vascular involvement was found only during work-up for arterial hypertension. This case highlights potentially asymptomatic nature of extensive vasculitis affecting large and medium-sized vessels in Cogan's disease. Careful screening is required to prevent life-threatening complications.

[Fingerprint microcystic dystrophy: Episodes of irregular astigmatism and their topographical representation]. / Distrofia en huella dactilar: brotes de astigmatismo irregular y su demostración topográfica.

CASE STUDY: A 44 year-old male patient suffering from painless bouts of blurred vision and with no visible ophthalmological repercussions initially. After one of these clinical episodes we managed to visualise fingerprint images in the anterior pole, as well as corneal, pachymetric and topographical changes, which in turn produce the symptomatic refractive changes. DISCUSSION: Fingerprint keratopathy is a condition diagnosed through recurring corneal erosion. The pathogenic origin of the condition-an altered epithelial basal membrane- may encourage the separation of the corneal epithelium from its underlying layers. Depending on whether this separation is partial or total, this will lead to spontaneous corneal erosion or, less frequently, episodes of blurred vision caused by oedema and corneal swelling.

[A case of atypical Cogan's syndrome with a steroid-responsive headache and multiple cranial neuropathy as the initial symptoms].

Cogan's syndrome (CS) is an autoimmune disorder characterized by non-syphilitic interstitial keratitis and progressive audiovestibular impairment. Haynes et al. modified diagnostic criteria for patients with other ocular or vestibular symptoms and suggested this to be atypical CS. We report the case of a 71-year-old man with atypical CS. He was referred to our hospital with a headache, bilateral facial nerve palsy, left episcleritis and bilateral sensorineural hearing loss. Serological test results for syphilis and antineutrophil cytoplasmic autoantibodies were negative. Cerebral MRI revealed sinusitis and pituitary swelling. Contrast-enhanced computed tomography (CT) of the aorta demonstrated thickening of the wall and stenosis of the aorta with pathological uptake on fluorodeoxyglucose positron emission tomography. Biopsy of the sinus mucosa exhibited angiitis of the arterioles, capillaries, and venules. Atypical CS was diagnosed on the basis of episcleritis, progressive sensorineural hearing loss and exclusion of other inflammatory diseases. Intravenous injection of 500mg/day methylprednisolone for 3 days was effective for alleviating the patient's symptoms, except for hearing loss, but the disease recurred during the tapering of prednisolone (PSL). Combined therapy with PSL (10 mg/day) and methotrexate (6 mg/week) helped achieve remission of the disease. CS is causative of cranial polyneuropathy, but diagnosis of the former is not always straightforward as in the cases of cranial polyneuropathy. It has been considered that CS is a subtype of polyarteritis nodosa (PN); however, the clinical signs and size of the affected vessels in the present patient are different from those in PN. It is postulated that CS is a vasculitic syndrome that should be distinguishable from PN.