Bilateral congenital agenesis of lacrimal glands in a Tunisian family.

BACKGROUND: Chronic corneal ulcers still pose etiological and therapeutic challenge. They are serious complications and often associated with poor functional prognosis. AIM: We report the case of a patient with bilateral and chronic corneal ulcer revealing a rare   familial   form   of   bilateral   agenesis   of   the   lacrimal   gland. CASES REPORT: A 39-year-old man was referred to our department for bilateralchronic and sterile ulcer. The tear break-up time was less than one second and the schirmer test detected no wetting in 5 minutes. He mentioned that lacrimation had been totally absent even when crying as was the case of his brother and his sister. Orbital echography showed absence of lacrimal gland. Orbital magnetic resonance imaging revealed absence of both lacrimal glands. Our patients were treated with permanent topical artificial tears. We performed also permanent occlusion of lower lachrymal poncti to preserve basic tear flow. CONCLUSION: Congenital lacrimal gland agenesis is rare. We report, to ourknowledge, the first case of Tunisian family with three patients suffering from bilateral lacrimal gland agenesis and the first documented familiarly cases diagnosed in adulthood.

Granulomatous uveitis and reactive arthritis as manifestations of post-streptococcal syndrome.

To report a case of bilateral granulomatous post-streptococcal syndrome uveitis in association with reactive arthritis as manifestation of post-streptococcal syndrome. To our knowledge, this could represent the first reported case in the literature. A 9-year-old girl, with no past ocular history, presented with a 5-day history of bilateral blurred vision, red eyes, photophobia and walking difficulties because of a right ankle pain. Ophthalmic examination disclosed a visual acuity limited to hand motion, mutton-fat keratic precipitates, anterior chamber cells and posterior synechiae in both eyes. Ocular pressure was normal. Physical examination showed a fever (38 °C), inflammatory ankle arthritis and scarlet fever (streptococcal lesion). Anti-streptococcal lysine O titer was 419 µ/ml. The patient was treated with topical steroids, cycloplegics, high-dose oral steroids and preventive course of penicillin with total improvement and no recurrence. Post-streptococcal syndrome should be considered in the etiology of acute bilateral granulomatous uveitis in children, and anti-streptococcal lysine O titer should be considered in serodiagnostic testing.

Central corneal thickness in a healthy Tunisian population.

AIM: To study the central corneal thickness of a Tunisian population and determine the influence of age, gender, axial length and refractive error on central corneal thickness (CCT) values. METHODS: An observational, cross-sectional study was conducted on 608 eyes of consecutive Tunisian patients without ophthalmic disease. Corneal tomography (Oculus Pentacam, USA) and a complete eye examination were performed on all patients. The relationship between the central corneal thickness values and variables of age, refractive error, axial length and gender was assessed. RESULTS: The mean central corneal thickness was 522±37.17µm (range 461 to 655 µm). No statistical association was found between central corneal thickness values and variables of age, refractive error, axial length and gender. CONCLUSIONS: The normal CCT value in the Tunisian population was of 522±37.17 µm. We have analyzed, for the first time, normal central corneal thickness values of a healthy Tunisian population.

Different Phenotypes in Pseudodominant Inherited Retinal Dystrophies.

Retinal dystrophies (RD) are a group of Mendelian disorders caused by rare genetic variations leading to blindness. A pathogenic variant may manifest in both dominant or recessive mode and clinical and genetic heterogeneity makes it difficult to establish a precise diagnosis. In this study, families with autosomal dominant RD in successive generations were identified, and we aimed to determine the disease's molecular origin in these consanguineous families. Whole exome sequencing was performed in the index patient of each family. The aim was to determine whether these cases truly represented examples of dominantly inherited RD, or whether another mode of inheritance might be applicable. Six potentially pathogenic variants in four genes were identified in four families. In index patient with enhanced S-cone syndrome in F1, we identified a new digenetic combination: a heterozygous variant p.[G51A];[=] in RHO and a homozygous pathogenic variant p.[R311Q];[R311Q] in NR2E3. Helicoid subretinal fibrosis associated with recessive NR2E3 variant p.[R311Q];[R311Q] was identified in F2. A new frameshift variant c.[105delG];[105delG] in RDH12 was found in F3 with cone-rod dystrophy. In F4, the compound heterozygous variants p.[R964*];[W758*] were observed in IMPG2 with a retinitis pigmentosa (RP) phenotype. We showed that both affected parents and the offspring, were homozygous for the same variants in all four families. Our results provide evidence that in consanguineous families, autosomal recessive can be transmitted as pseudodominant inheritance in RD patients, and further extend our knowledge of pathogenic variants in RD genes.

Polypoidal choroidal vasculopathy in a patient with angioid streaks treated by bevacizumab.

OBJECTIVE: We report the association of polypoid choroidal vasculopathy (PVC) with angioid streaks (AS) secondary to pseudoxanthoma elasticum (PXE) treated by intravitreal injection of bevacizumab. CASE REPORT: A 50-year-old patient, followed in dermatology for a PXE, who consulted for a consulted for a decreased vision in his right eye (RE) for a month. On examination, best corrected visual acuity (BCVA) was at 1/20 P14 in the RE and at 8/10 P2 in the left eye (LE). Fundus examination revealed AS in both eyes, large patches of exudate at the posterior pole with retinal hemorrhages in the RE. Fluorescein angiography (FA) showed constant hypofluorescence by mask effect due to exudates and macular early hyperfluorescence with late diffusion associated with small hyperfluorescent lesions in the RE. We suspected CNV type 2. Macular Spectral Domain optical coherence tomography (SD-OCT) showed significant retinal infiltration with pre-epithelial hyper-reflectivity bracing the diagnosis of type 2 CNV. In view of the importance of exudates and intra-retinal infiltration, we completed by indocyanine green angiography (ICGA) which showed hypercyanecent vascular dilations grouped in clusters of grapes relevant to an associated VPC. The patient received eight monthly intravitreal (IVT) injections of bevacizumab with good anatomical evolution. At 10 months, visual acuity was 1/10 with disappearance of exudates and retinal infiltration. CONCLUSION: Patients with AS should receive regular follow-up given the risk of CNV but also of VPC, especially in cases of PXE. Multimodal imaging is of great help and ICGA remains inescapable.

Genetic spectrum of retinal dystrophies in Tunisia.

We report the molecular basis of the largest Tunisian cohort with inherited retinal dystrophies (IRD) reported to date, identify disease-causing pathogenic variants and describe genotype-phenotype correlations. A subset of 26 families from a cohort of 73 families with clinical diagnosis of autosomal recessive IRD (AR-IRD) excluding Usher syndrome was analyzed by whole exome sequencing and autozygosity mapping. Causative pathogenic variants were identified in 50 families (68.4%), 42% of which were novel. The most prevalent pathogenic variants were observed in ABCA4 (14%) and RPE65, CRB1 and CERKL (8% each). 26 variants (8 novel and 18 known) in 19 genes were identified in 26 families (14 missense substitutions, 5 deletions, 4 nonsense pathogenic variants and 3 splice site variants), with further allelic heterogeneity arising from different pathogenic variants in the same gene. The most common phenotype in our cohort is retinitis pigmentosa (23%) and cone rod dystrophy (23%) followed by Leber congenital amaurosis (19.2%). We report the association of new disease phenotypes. This research was carried out in Tunisian patients with IRD in order to delineate the genetic population architecture.

Correction: Habibi I. et al. "Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)" Genes, 2019, 10, 953.

The authors wish to make a correction to the published version of their paper [...].

Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB).

Mutations in BEST1 cause several phenotypes including autosomal dominant (AD) Best vitelliform macular dystrophy type 2 (BVMD), AD vitreo-retino-choroidopathy (ADVIRC), and retinitis pigmentosa-50 (RP50). A rare subtype of Bestrophinopathy exists with biallelic mutations in BEST1. Its frequency is estimated to be 1/1,000,000 individuals. Here we report 6 families and searched for a genotype-phenotype correlation. All patients were referred due to reduced best-corrected visual acuity (BCVA), ranging from 0.1/10 to 3/10. They all showed vitelliform lesions located at the macula, sometimes extending into the midperiphery, along the vessels and the optic disc. Onset of the disease varied from the age of 3 to 25 years. Electrooculogram (EOG) revealed reduction in the EOG light rise in all patients. Molecular analysis revealed previously reported mutations p.(E35K);(E35K), p.(L31M);(L31M), p.(R141H);(A195V), p.(R202W);(R202W), and p.(Q220*);(Q220*) in five families. One family showed a novel mutation: p.(E167G);(E167G). All mutations were heterozygous in the parents. In one family, heterozygous children showed various reductions in the EOG light rise and autofluorescent deposits. Autosomal recessive Bestrophinopathy (ARB), although rare, can be recognized by its phenotype and should be validated by molecular analysis. Genotype-phenotype correlations are difficult to establish and will require the analysis of additional cases.

Identifying mutations in Tunisian families with retinal dystrophy.

Retinal dystrophies (RD) are a rare genetic disorder with high genetic heterogeneity. This study aimed at identifying disease-causing variants in fifteen consanguineous Tunisian families. Full ophthalmic examination was performed. Index patients were subjected to IROme analysis or whole exome sequencing followed by homozygosity mapping. All detected variations were confirmed by direct Sanger sequencing. Mutation analysis in our patients revealed two compound heterozygous mutations p.(R91W);(V172D) in RPE65, and five novel homozygous mutations: p.R765C in CNGB1, p.H337R in PDE6B, splice site variant c.1129-2A > G and c.678_681delGAAG in FAM161A and c.1133 + 3_1133 + 6delAAGT in CERKL. The latter mutation impacts pre-mRNA splicing of CERKL. The other changes detected were six previously reported mutations in CNGB3 (p.R203*), ABCA4 (p.W782*), NR2E3 (p.R311Q), RPE65 (p.H182Y), PROM1 (c.1354dupT) and EYS (c.5928-2A > G). Segregation analysis in each family showed that all affected individuals were homozygotes and unaffected individuals were either heterozygote carriers or homozygous wild type allele. These results confirm the involvement of a large number of genes in RD in the Tunisian population.