Autosomal recessive congenital hereditary corneal dystrophy associated with a novel SLC4A11 mutation in two consanguineous Tunisian families.

BACKGROUND: Autosomal recessive congenital hereditary corneal dystrophy (CHED) is a rare isolated developmental anomaly of the eye characterised by diffuse bilateral corneal clouding that may lead to visual impairment requiring corneal transplantation. CHED is known to be caused by mutations in the solute carrier family 4 member 11 (SLC4A11) gene which encodes a membrane transporter protein (sodium bicarbonate transporter-like solute carrier family 4 member 11). METHODS: To identify SLC4A11 gene mutations associated with CHED (OMIM: #217700), genomic DNA was extracted from whole blood and sequenced for all exons and intron-exon boundaries in two large Tunisian families. RESULTS: A novel deletion SLC4A11 mutation (p. Leu479del; c.1434_1436del) is responsible for CHED in both analysed families. This non-frameshift mutation was found in a homozygous state in affected members and heterozygous in non-affected members. In silico analysis largely support the pathogenicity of this alteration that may leads to stromal oedema by disrupting the osmolarity balance. Being localised to a region of alpha-helical secondary structure, Leu479 deletion may induce protein-compromising structural rearrangements. CONCLUSION: To the best of our knowledge, this is the first clinical and genetic study exploring CHED in Tunisia. The present work also expands the list of pathogenic genotypes in SLC4A11 gene and its associated clinical diagnosis giving more insights into genotype-phenotype correlations.

Disseminated lymphoblastic lymphoma revealed by an isolated third cranial nerve palsy.

Dysfunction of the third cranial nerve can be provoked by a number of different conditions. An isolated cranial neuropathy as a first clinical sign of a non-Hodgkin lymphoma is very infrequent. We represent here an atypical case of lymphoblastic lymphoma revealed by an isolated third cranial nerve palsy. The patient was managed by alternating cycles of cyclophosphamide, vincristine, and prednisone. She made a full recovery with a complete resolution of the symptomatology.

Isolated optic nerve infiltration as a site of relapse of acute lymphoblastic leukemia.

Optic nerve infiltration is relatively rare in acute lymphoblastic leukemia. We present a case of a -53 year-old-man who was diagnosed with T- acute lymphoblastic leukemia (ALL). The patient was treated with ALL national protocol and the central nervous system (CNS) prophylactic management. On treatment, the patient presented with sudden severe vision deterioration of both eyes. Fundoscopic examination of the eye and magnetic resonance imaging of the orbits were in favor of an infiltration of the optical nerve. An isolated extramedullary relapse of the optical nerve was retained. The patient was treated with salvage chemotherapy systematic and intrathecal. Waiting forthe beginning of radiotherapy, the patient presented a bone marrow relapse. He died of a severe hemorrhagic syndrome. Conclusion: Optic nerve leukemic infiltration has a severe prognosis. Ophthalmic assessment is essential in patients with ALL in order to diagnose an early ocular involvement and the patient's vision can be preserved if treatment is initiated promptly.

Presumed Tuberculous uveitis: clinical features and management.

AIM: To illustrate the various clinical features and management of presumed tuberculous uveitis in an endemic area in Tunisia. METHODS: This is a retrospective study including 14 patients (26 eyes) diagnosed with presumed tuberculous uveitis at the Department of Ophthalmology Habib Bourguiba University Hospital of Sfax-Tunisia. RESULTS: Mean age at onset was 31.7 years. Uveitis was bilateral in 86 % of cases (12 eyes). Panuveitis was the most common manifestation and represented 50% of cases (13 eyes). Ocular findings include mutton-fat keratic precipitates in 35% of cases (9 eyes), posterior synechiae in 31% of cases (8 eyes), vitritis in 81% of cases (21eyes), multifocal choroiditis in 23% of cases (6 eyes), periphlebitis in 27% of cases (7 eyes), and macular edema in 42% of cases (11eyes). Anti-tubercular treatment was prescribed in all patients and was associated with systemic corticosteroids in 71% of cases (10 patients). After a mean follow-up of 16.27 months (range, 6-36), inflammation was controlled with improvement in visual acuity. Recurrence developed in 7 % of cases (1 patient). CONCLUSION: In the present study, posterior synechiae, vitritis, multifocal choroiditis, and retinal vasculitis are the most common manifestations of tuberculous uveitis in tuberculosis endemic area in Tunisia. These manifestations are suggestive of a tubercular cause of uveitis and merit specific treatment.

Novel BEST1 gene mutations associated with two different forms of macular dystrophy in Tunisian families.

BACKGROUND: Epidemiological studies of hereditary eye diseases allowed us to identify two Tunisian families suffering from macular dystrophies: Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). The purpose of the current study was to investigate the clinical characteristics and the underlying genetics of these two forms of macular dystrophy. METHODS: Complete ophthalmic examination was performed including optical coherence tomography, electroretinography, electrooculography and autofluoresence imaging in all patients. Genomic DNA was extracted from peripheral blood collected from patients and family members. RESULTS: Sanger sequencing of all exons of the BEST1 gene in both families identified two new mutations: a missense mutation c.C91A [p.L31 M] at the N-terminal transmembrane domain within the ARB family and a nonsense mutation C1550G (p.S517X) in the C-terminal domain segregating in the BVMD family. CONCLUSIONS: Several mutations of the BEST1 gene have been reported which are responsible for numerous ocular pathologies. To the best of our knowledge, it is the first time we report mutations in this gene in Tunisian families presenting different forms of macular dystrophy. Our report also expands the list of pathogenic BEST1 genotypes and the associated clinical diagnosis.

Swept-Source Optical Coherence Tomography Angiography in West Nile Virus Chorioretinitis and Associated Occlusive Retinal Vasculitis.

A 65-year-old man with diabetes and a history of fever of unknown origin 2 weeks earlier complained of sudden decreased vision in the left eye. The patient was diagnosed with bilateral West Nile virus (WNV) chorioretinitis associated with occlusive retinal vasculitis in the left eye. Swept-source optical coherence tomography angiography (SS-OCTA) of the left eye showed extensive, well-delineated, hypointense non-perfusion areas and perifoveal capillary arcade disruption in the superficial capillary plexus, as well as larger non-perfusion areas, capillary rarefaction, and diffuse capillary network attenuation and disorganization in the deep capillary plexus. OCTA may be a valuable tool for noninvasively assessing occlusive retinal vasculitis associated with WNV infection. It allows an accurate detection and precise delineation of areas of retinal capillary nonperfusion in both the superficial and deep capillary plexuses. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:672-675.].

Ocular involvement associated with varicella in adults.

BACKGROUND: Varicella is a common infectious disease primarily of childhood that is usually benign and self-limited. It is, however, increasingly seen in adults who are at a higher risk of severe infection. Ocular complications of varicella are relatively uncommon and have been rarely described in adults. We describe herein five adults who developed ocular involvement in association with primary varicella-zoster virus infection. FINDINGS: Ocular manifestations included acute anterior uveitis in four eyes, with associated stromal keratitis in one of them, epithelial ulcerative keratitis in the two eyes of one patient, and acute retinal necrosis in one eye. One patient with acute anterior uveitis was treated with topical steroids and cycloplegic agents. The four other patients received topical or systemic antiviral drugs, with subsequent resolution of acute ocular inflammatory disease. CONCLUSIONS: The spectrum of chickenpox-associated ocular complications in adults is wide. Early diagnosis and appropriate management are mandatory to improve visual outcome.

The spectrum of presumed tubercular uveitis in Tunisia, North Africa.

The purpose of this study was to analyze the spectrum of presumed tubercular uveitis in Tunisia, North Africa. We retrospectively reviewed the clinical records of 38 patients (65 eyes) diagnosed with presumed tubercular uveitis at two referral centers in Tunisia, between January 2009 and December 2011. Mean age at presentation was 42.7 years. Twenty-four patients were women (63.2%) and 14 (36.8%) were men. Twenty-three eyes (35.4%) had posterior uveitis, 21 eyes (32.3%) had intermediate uveitis, 13 eyes (20%) had panuveitis, and 8 eyes (12.3%) had anterior uveitis. Ocular findings included vitritis in 67.7% of eyes, posterior synechiae in 47.7%, multifocal non-serpiginoid choroiditis in 23.1%, multifocal serpiginoid choroiditis in 21.5%, periphlebitis in 21.5%, and mutton-fat keratic precipitates in 20%. Anti-tubercular treatment was prescribed in 33 patients (86.8%) and was associated with systemic corticosteroids in 20 patients (52.6%) and periocular injections of corticosteroids in four patients (10.5%). After a mean follow-up of 14.2 months (range, 10-58), inflammation was controlled, with a significant improvement in visual acuity (VA) (p = 0.028). However, recurrences developed in two patients (5.3%). Final VA was better than 20/40 in 27 eyes (41.5%) and less than 20/200 in five eyes (7.7%). In Tunisia, all anatomic types are possible in tuberculosis-associated uveitis, but posterior and intermediate uveitis are more frequent. Vitritis, posterior synechiae, multifocal serpiginoid or non-serpiginoid choroiditis, and periphlebitis are the most common manifestations.

Visual loss associated with rickettsial disease.

UNLABELLED: Abstract Purpose: To characterize and analyze ocular involvement associated with visual loss in a cohort of patients with rickettsial disease. METHODS: Retrospective study of 16 eyes of 14 patients. RESULTS: Mean initial visual acuity (VA) was 20/63 (range, 20/800-20/25). White retinal lesions infiltrating inner retina was the most common finding occurring in 14 eyes (87.5%). It was associated with a serous retinal detachment (SRD), accurately detectable by optical coherence tomography, in 11 eyes (78.6%). Other findings included optic neuropathy in 7 eyes (43.75%), cystoid macular edema in 1 eye (6.25%), branch retinal artery occlusion in 1 eye (6.25%), and choroidal neovascularization in 1 eye (6.25%). Thirteen patients were treated with a 2-week course of oral doxycycline 200 mg/day. Mean final VA was 20/40. CONCLUSIONS: Inner retinitis, associated with mild vitritis and SRD, and optic neuropathy are the most common vision-threatening ocular manifestations of rickettsial disease.

Reinforcement of a minor alternative splicing event in MYO7A due to a missense mutation results in a mild form of retinopathy and deafness.

PURPOSE: Recessive mutations of the myosin VIIA (MYO7A) gene are reported to be responsible for both a deaf-blindness syndrome (Usher type 1B [USH1B] and atypical Usher syndrome) and nonsyndromic hearing loss (HL; Deafness, Neurosensory, Autosomal Recessive 2 [DFNB2]). The existence of DFNB2 is controversial, and often there is no relationship between the type and location of the MYO7A mutations corresponding to the USH1B and DFNB2 phenotype. We investigated the molecular determinant of a mild form of retinopathy in association with a subtle splicing modulation of MYO7A mRNA. METHODS: Affected members underwent detailed audiologic and ocular characterization. DNA samples from family members were genotyped with polymorphic microsatellite markers. Sequencing of MYO7A was performed. Endogenous lymphoid RNA analysis and a splicing minigene assay were used to study the effect of the c.1935G>A mutation. RESULTS: Funduscopy showed mild retinitis pigmentosa in adults with HL. Microsatellite analysis showed linkage to markers in the region on chromosome 11q13.5. Sequencing of MYO7A revealed a mutation in the last nucleotide of exon 16 (c.1935G>A), which corresponds to a substitution of a methionine to an isoleucine residue at amino acid 645 of the myosin VIIA. However, structural prediction of the molecular model of myosin VIIA shows that this amino acid replacement induces only minor structural changes in the immediate environment of the mutation and thus does not alter the overall native structure. We found that, although predominantly included in mature mRNA, exon 16 is in fact alternatively spliced in control cells and that the mutation at the very last position is associated with a switch toward a predominant exclusion of that exon. This observation was further supported using a splicing minigene transfection assay; the c.1935G>A mutation was found to trigger a partial impairment of the adjacent donor splice site, suggesting that the unique change at the last position of the exon is responsible for the enhanced exon exclusion in this family. CONCLUSIONS: This study shows how an exonic mutation that weakens the 5' splice site enhances a minor alternative splicing without abolishing a complete exclusion of the exon and therefore causes a less severe retinitis pigmentosa than the USH1B-associated alleles. It would be interesting to examine a possible correlation between intrafamilial phenotypic variability and the subtle variation in exon 16 inclusion, probably related to genetic background specificities.

[Bilateral retinal detachments. Risk factors and treatment efficacy: 11 cases]. / Décollements de rétine bilatéraux. Facteurs de risques et efficacité thérapeutique: évaluation chez 11 patients.

PURPOSE: The purpose of our study was to evaluate the incidence of bilateral retinal detachments and to analyze the risk factors for it and the anatomic and functional results of treatment. METHODS: Retinal detachment can be discovered in both eyes during an initial consultation. In other cases, retinal detachment may be seen in the second eye during follow-up of the first eye. RESULTS: Bilateral retinal detachments account for 11.7% of the retinal detachments in our hospital. Many factors are involved in bilateral detachment, including myopia and degenerative lesions. Treatment depends on the type of detachment. CONCLUSION: Treatment of bilateral detachments is difficult and depends on the specific type of detachment. Relatively young men are most at risk for bilateral detachments.

[Retrobulbar anesthesia during keratolplasty]. / Anesthesie locoregionale dans la keratoplastie.

AIM: A restrospective study was carried in order to evaluate the efficacy and safety of retrobulbar anaesthesia during keratoplasty. METHODS: Of 250 consecutive keratoplasty, 30 (12%) were performed under retrobulbar anaesthesia. Patients received a mean volume of 12 ml, composed of etidocaine (2/3), bupicaine (1/3) and hyaluronidase. Ocular compression duration was at least 20 minutes. RESULTS: Surgery was found painless by 90% of patients. Akinesia was complete in 80% of cases. CONCLUSION: Theses results demonstrate that retrobulbar anaesthesia may be recommended to this type of surgery.

[Ocular manifestations of pseudoxanthoma elasticum]. / Atteinte oculaire au cours du pseudoxanthome élastique.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a hereditary disease characterized by skin, ocular, and cardiovascular lesions. Its prognosis depends mainly on the ocular and vascular lesions. METHODS: This study included 11 patients with PXE. All patients had an ophthalmologic examination. RESULTS: All patients had ocular lesions. Seven (63%) had angioid streaks and two, macular lesions. One patient had bilateral intrapapillary drusen (of the optic nerve head). CONCLUSION: Ocular lesions in PXE had substantial diagnostic value. Ocular complications affect functional prognosis. These patients must undergo routine ophthalmologic examinations to look for ocular manifestations and their complications.

[Ophthalmic manifestations of lipoid proteinosis]. / Manifestations ophtalmologiques de la hyalinose cutanéo-muqueuse.

INTRODUCTION: Lipoid proteinosis (LP), also known as hyalinosis (or lipoidosis) cutis et mucosae or Urbach-Wiethe disease, is a rare autosomal recessive disorder. It is associated with deposits of protein-lipid complexes in various tissues including the skin and mucous membranes. Ophthalmologic manifestations are frequent and can affect visual prognosis. CASE: This 28-year-old patient presented vesiculobullous lesions of the face that developed into varioloid scars associated with hoarseness. Ophthalmologic examination revealed unilateral lesions including hyaline deposits on the palpebral margins, iris, and trabecular zone, complicated by uveitis, cataract, and glaucoma, which caused the functional loss of the left eye. Histological examination of a cutaneous biopsy confirmed the diagnosis. DISCUSSION: Involvement of the eyelids is characteristic, and moniliform blepharosis is pathognomonic and frequent. This case featured a rare intraocular form (uveitis). Deposits may be found on the conjunctiva, cornea, trabecula and Bruch membrane. Conjunctival or cutaneous biopsy confirms the diagnosis. Available treatment is quite limited.

[Ophtalmologic manifestations of the xeroderma pigmentosum]. / Les manifestations ophtalmologiques du xéroderma pigmentosum.

Xéroderma pigmentosum (XP) is a rare genetic disease characterised by defective repair of DNA damage. We report a retrospective study of the ophtalmologic manifestations of 16 patients with xéroderma pigmentosum, the ophtalmologic manifestations were present in 62% of cases. The age of patients was 7 to 22 years. Photophobia were seen in all patients. Multiple tumors were seen with 5 squamous cell carcinoma. Tumor size was 1 to 6 cm. Ocular involvement occurs in up to 80% of cases of XP. Infection, néoplasia, conjonctiva are the most commun finding. Patients with XP can acquire squamous cell carcinoma at an early age.

[Peribulbar anaesthesia for strabismus surgery]. / Anesthesie locale pour la chirurgie de strabisme.

BACKGROUND: Strabismus surgery is underwent with general anaesthesia since it's a paediatric surgery in the majority of cases. The aim of our study is to analyse the safety and tolerance of peribulbar anaesthesia for strabismus surgery. PATIENTS AND METHODS: sixty two patients underwent strabismus surgery with a peribulbar anaesthesia. All patients had premedication the evening before and two hours bef6re the surgery. All patients were examined to evaluate the efficacy and the safety of such anaesthesia. RESULTS: The main age was 31,5 years. Forty patients were female and twenty two were male. None had report pain. Three patients report just incomfort during surgery. Orthoptic results were acceptable. CONCLUSION: Peribulbar anaesthesia has shown to be an effective alternative for general anaesthesia for strabismus surgery in an attempt to reduce the morbidity and mortality. It take importance particularly in patients of high-risk characteristics and in monocular surgery.