Gender differences in the association of ELMO1 genetic variants with type 2 diabetes in Tunisian Arabs.

PURPOSE: Polymorphisms of the engulfment and cell motility 1 (ELMO1) gene were recently associated with type 2 diabetes (T2DM) and its complications. We investigated the association of rs10255208, rs7782979, and rs2041801 ELMO1 gene variants with T2DM in Tunisian Arabs. METHODS: Subjects comprised 900 T2DM patients and 600 normoglycemic controls. ELMO1 genotyping was done by PCR-RFLP; the contribution of ELMO1 variants to T2DM was analyzed by Haploview and regression analysis. RESULTS: Minor allele frequencies of rs7782979 and rs10255208 ELMO1 variants were significantly higher among unselected T2DM cases than controls, and significant differences in the distribution of rs7782979 genotypes were seen between T2DM cases and control subjects, which was seen in male but not female subjects. Three-locus ELMO1 haplotype analysis identified haplotype GAA to be positively associated, and haplotypes GCA, AAA, and GCG to be negatively associated with T2DM. The distribution of these haplotypes was gender-dependent for some (GCA, GCG, AAG), and gender-independent for others (GAA, AAA). This translated into altered risk of T2DM in male or female subjects, which persisted after adjusting for BMI, systolic and diastolic blood pressure, and serum lipid profile. CONCLUSION: These results confirm role for ELMO1 as T2DM susceptibility locus, which appears to be gender-dependent.

Successful management of dry eye disease with a new eye drop formulation combining hyaluronic acid, trehalose, and N-acetyl-aspartyl-glutamic acid (NAAGA).

PURPOSE: To assess the clinical efficacy and safety of T2769, a new preservative-free eye drop combining hyaluronic acid (HA), trehalose and N-acetyl-aspartyl-glutamic acid (NAAGA), in dry eye patients. PATIENTS AND METHODS: This was a multicenter, non-comparative, open-label study. After a run-in period with NaCl 0.9% solution, 62 patients with moderate-to-severe dry eye disease (DED) were included and treated with T2769, 3 to 6 times/day for 42 days. The primary efficacy endpoint was the change in global ocular symptomatology assessed on a visual analog scale between Day 1 (D1) and D42. Other efficacy endpoints included ocular surface disease index (OSDI), soothing sensation, individual dry eye symptoms, conjunctival hyperemia, global ocular staining, tear break-up time, Schirmer test, and global efficacy assessed by the investigator. Safety was assessed throughout the study. RESULTS: A marked reduction in ocular symptomatology was observed from D1 to D42 with a mean change of -55.9±23.1mm (P<0.001). This was accompanied by a mean change in OSDI score from baseline of -44.6±15.9 (P<0.001) and a substantial soothing sensation in 82.3% of patients. Clinically significant improvements were observed for all ocular symptoms (mainly burning/irritation, stinging/pain, feeling of ocular dryness, foreign body sensation, itching/pruritus). Conjunctival hyperemia significantly decreased in 96.8% of patients (56.5% displayed no conjunctival hyperemia at D42 versus 0% at baseline). All signs and symptoms improved by D14 and further improved at D42. Investigators assessed the ocular efficacy of T2769 as very satisfactory or satisfactory for 91.9% of patients at D42. T2769 was well tolerated, with no ocular adverse events and only a few ocular symptoms upon instillation. CONCLUSION: Management of moderate-to-severe DED patients with the new formulation T2769, combining NAAGA to HA and trehalose, led to rapid and significant improvements in dry eye signs and symptoms with good tolerability.

Ocular tuberculosis presenting with a conjunctival granuloma.

An 18-year-old female patient was referred with complaints of tearing and redness in the left eye for 3 months after a mild ocular trauma with a turkey feather. She was treated with topical antibiotics and corticosteroids with no improvement. Slit-lamp examination of the left eye showed a vascularized lesion with a polypoidal appearance due to multiple contiguous micronodules on the temporal and inferior bulbar conjunctiva. Results of the anterior and posterior segment examination were unremarkable in both eyes. A biopsy specimen of the conjunctival mass showed multiple tuberculoid granulomas composed of epithelioid histiocytes with associated Langhan's type multinucleate giant cells and a necrotic nodule surrounded by histiocytes and giant cells. The Mantoux test was positive with induration of 15mm. The patient was prescribed antituberculosis therapy. Three months after treatment initiation, the conjunctival lesions had resolved. Mycobacterium tuberculosis should be considered in cases of unilateral chronic recalcitrant conjunctivitis. Biopsy of a conjunctival mass is of utmost importance to establish a definite diagnosis.

Technical considerations of endovascular management of true visceral artery aneurysms.

BACKGROUND: True visceral artery aneurysms are potentially complex to treat but with advances in technology and increasing interventional radiology expertise over the past decade are now increasingly the domain of the interventional radiologist. BODY: The interventional approach is based on localization of the aneurysm and identification of the anatomical determinants to treat these lesions to prevent aneurysm rupture. Several different endovascular techniques are available and should be selected carefully, dependent on the aneurysm morphology. Standard endovascular treatment options include stent-graft placement and trans-arterial embolisation. Different strategies are divided into parent artery preservation and parent artery sacrifice techniques. Endovascular device innovations now include multilayer flow-diverting stents, double-layer micromesh stents, double-lumen balloons and microvascular plugs and are also associated with high rates of technical success. CONCLUSION: Complex techniques such as stent-assisted coiling and balloon-remodeling techniques are useful techniques and require advanced embolisation skills and are further described.

[Role of optical coherence tomography in unilateral amblyopia]. / Apport de la tomographie en cohérence optique dans l'amblyopie unilatérale.

PURPOSE: To compare the macular and papillary parameters on optical coherence tomography (OCT) between the amblyopic eye and the healthy eye in subjects with unilateral strabismic or anisometropic amblyopia. PATIENTS AND METHODS: This is a cross-sectional and comparative study carried out over two years, from April 1, 2019, to March 31, 2021. We included patients aged over 5years, followed for unilateral amblyopia, free of any neurological and/or ocular pathology. The evaluation of the macular and papillary parameters in the amblyopic and healthy eyes was performed with Swept-Source Optical Coherence Tomography (OCT-SS). The parameters were compared according to age group and type of amblyopia. RESULTS: We collected 50 patients, 29 children, and 21 adults, with a mean age of 19.8years. Amblyopia was secondary to anisometropia in 40 patients and strabismus in 10 patients. Analysis of macular tomographic parameters found no significant difference between amblyopic eyes and healthy eyes for mean macular thickness (P=0.86), central macular thickness (P=0.86), or mean macular volume (P=0.54). The mean retinal peripapillary fiber thickness (RNFL) was 107.48µm in the amblyopic eye and 103.8µm in the healthy eye, with a statistically significant difference (P<0.001). This significant thickening of the RNFL in amblyopic eyes was present in adults (P<0.001), children (P<0.001), anisometropic (P<0.001), and strabismic amblyopia (P=0.024). Analysis of the other optic nerve head parameters revealed no significant difference between amblyopic eyes and healthy eyes in terms of optic disc surface area (P=0.89), neuro-retinal annulus surface area (P=0.47), vertical (P=0.98) or horizontal (P=0.74) cup to disc ratio. CONCLUSION: Amblyopia is accompanied by thickening of the peripapillary retinal fibers without macular repercussions. However, larger prospective studies are needed to confirm these results.

IRVAN syndrome: A retrospective review of 9 cases from Tunisia.

PURPOSE: To describe clinical features, relevant imaging findings, disease course, and response to treatment in 9 patients (18 eyes) with idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome. METHODS: Retrospective review of the charts of nine patients (18 eyes) diagnosed with IRVAN syndrome at Fattouma Bourguiba University Hospital, Monastir, Tunisia, from January 1, 2011 to January 1, 2022. RESULTS: Nine patients were included with bilateral involvement in all cases. Mean initial best-corrected visual acuity (VA) was 20/32 (range, 20/1600-20/20). Clinical findings at presentation included vitreous cells (10 eyes, 55.6%), peripapillary exudates (12 eyes, 66.7%), partial or complete macular star (11 eyes, 61.1%), and vascular sheathing (11 eyes, 61.1%). Fluorescein angiography showed arteriolar aneurysms (18 eyes, 100%), areas of peripheral capillary non-perfusion (16 eyes, 88.9%), and retinal neovascularization (6 eyes, 33.3%). Optical coherence tomography showed macular edema in 5 eyes (27.8%). Optical coherence tomography angiography of the optic disc demonstrated papillary aneurysms in 4 eyes of 2 patients. Indocyanine green angiography showed retinal arteriolar aneurysmal dilatations in 4 eyes of 2 patients. Ten eyes (55.6%) had stage 2 disease, 6 eyes (33.3%) had stage 3, and 2 eyes (11.1%) had stage 1. Treatment modalities included peripheral photocoagulation (16 eyes, 88.9%), intravitreal bevacizumab (4 eyes, 22.2%), and intravitreal triamcinolone acetonide (1 eye, 5.6%). Mean final best-corrected VA was 20/32 (range, 20/600-20/20). Ocular complications included vitreous hemorrhage in 3 eyes (16.7%), branch retinal artery occlusion in 2 eyes (11.1%) and submacular fibrosis in 3 eyes (16.7%). CONCLUSION: IRVAN syndrome should be highly suspected in patients with peripapillary exudates associated with vascular sheathing and vitreous cells. Multimodal imaging confirms the diagnosis by showing retinal macroaneurysms. Early treatment of macular edema and/or peripheral retinal non-perfusion is mandatory to improve prognosis.

Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency.

We recently demonstrated early metabolic alterations in the dystrophin-deficient mdx heart that precede overt cardiomyopathy and may represent an early "subclinical" signature of a defective nitric oxide (NO)/cGMP pathway. In this study, we used genetic and pharmacological approaches to test the hypothesis that enhancing cGMP, downstream of NO formation, improves the contractile function, energy metabolism, and sarcolemmal integrity of the mdx heart. We first generated mdx mice overexpressing, in a cardiomyocyte-specific manner, guanylyl cyclase (GC) (mdx/GC(+/0)). When perfused ex vivo in the working mode, 12- and 20-week-old hearts maintained their contractile performance, as opposed to the severe deterioration observed in age-matched mdx hearts, which also displayed two to three times more lactate dehydrogenase release than mdx/GC(+/0). At the metabolic level, mdx/GC(+/0) displayed a pattern of substrate selection for energy production that was similar to that of their mdx counterparts, but levels of citric acid cycle intermediates were significantly higher (36 +/- 8%), suggesting improved mitochondrial function. Finally, the ability of dystrophin-deficient hearts to resist sarcolemmal damage induced in vivo by increasing the cardiac workload acutely with isoproterenol was enhanced by the presence of the transgene and even more so by inhibiting cGMP breakdown using the phosphodiesterase inhibitor sildenafil (44.4 +/- 1.0% reduction in cardiomyocyte damage). Overall, these findings demonstrate that enhancing cGMP signaling, specifically downstream and independent of NO formation, in the dystrophin-deficient heart improves contractile performance, myocardial metabolic status, and sarcolemmal integrity and thus constitutes a potential clinical avenue for the treatment of the dystrophin-related cardiomyopathies.

Retinal abscess: case report of an uncommon evolution.

We report a case of focal subretinal abscess in a 27-year-old diabetic man presenting with Staphylococcus sepsis. The follow-up study was based on visual acuity (VA), fundus photography, fluorescein angiography, ultrasound and optical coherence tomography, and an intravenous specific antibiotic was administered with an unusual good outcome.

[Specular microscopy findings in active uveitis]. / Résultats de la microscopie spéculaire au cours des uvéites actives.

PURPOSE: To study the effect of ocular inflammation in active uveitis on the corneal endothelium. MATERIALS AND METHODS: This is a prospective cross-sectional study involving 63 eyes of 38 patients with active newly-diagnosed uveitis. Eighty-four eyes of 42 non-uveitic subjects served as a control group. All patients underwent detailed ophthalmic examination, laser flare photometry, and non-contact specular microscopy. Eyes with uveitis had a follow-up visit at one month after initiation of treatment, including laser flare photometry and specular microscopy. RESULTS: The mean age of the active uveitis patients was 33 (range: 9-67 years) with 21 men (55%) and 17 women (45%). For the uveitis patients at baseline, the mean flare value was 32ph/ms (range: 15-100ph/ms) with flare photometry value ≥50ph/ms in 13 eyes (21%) and<50ph/ms in 50 eyes (79%). At baseline, cell density (CD) of the uveitis patients was similar to CD in control eyes (p꞊0.16). The percent of hexagonality was significantly lower (p<0.0001), and the coefficient of variance (CV) (p<0.0001) and central corneal thickness (CCT) (p<0.0001) were significantly higher than in the control group. After one month, there was a significant decrease in flare photometry values (p<0.0001), with a mean flare value of 14.5ph/ms (range: 4-60ph/ms). In the active uveitis group, the overall results of specular microscopy did not significantly vary between the initial examination and the 1-month examination. For eyes with flare photometry value ≥50ph/ms at baseline, CD and hexagonal cell count significantly increased on the 1-month examination (p꞊0.01 and p꞊0.02 respectively), while CV and CCT decreased significantly at the one-month follow-up visit (p꞊0.007/p꞊0.03 respectively). For eyes with flare photometry value at baseline <50ph/ms, there was no significant differences in specular microscopy results between the initial examination and the 1-month examination. CONCLUSIONS: In eyes with newly-diagnosed uveitis and active anterior chamber inflammation, specular microscopy shows transient qualitative abnormalities of the corneal endothelium that depend on the severity of the anterior chamber inflammation as measured by the laser flare meter.

Cross-validation of the Tunisian version of the National Eye Institute Visual Function Questionnaire 25.

INTRODUCTION: The goal of our study was to create a cross-cultural adaptation of the questionnaire « National Eye Institute Visual Function Questionnaire ¼ (NEI-VFQ-25) for the Tunisian population (Tu-VFQ-25) and to test its psychometric properties in a group of patients with chronic uveitis. PATIENTS AND METHODS: The study consisted of two steps. The first was translation of the NEI-VFQ-25 and its cross-cultural adaptation to the Tunisian dialect (Tu-VFQ-25) according to the guidelines of Beaton et al. The second step consisted of studying the psychometric properties of the Tu-VFQ-25. Enrolled patients, diagnosed with chronic uveitis, were interviewed face-to-face by two different investigators, followed by a telephone interview by the first investigator 48hours later. Feasibility, internal consistency and reproducibility of the Tu-VFQ-25 were then tested using statistical methods. RESULTS: The mean time taken to administrate the questionnaire to each of the 45 patients was 11min 40 s (± 2min 24 s). Internal consistency was acceptable, with Cronbach's alpha coefficients above 0.7 except the "Ocular Pain" and "Driving" subscales (0.645 and 0.559 respectively). Inter-observer reliability was excellent, with intra-class correlation coefficients (ICC) ranging from 0.857 to 0.985 for all subscales. Test-retest reliability, assessed for 43 patients, was good to excellent, with ICC above 0.80 for all subscales except "General Vision," which had a value of 0.786. CONCLUSION: As with previous versions, the Tu-VFQ-25 is an easy and reliable tool for assessing vision-related quality of life of Tunisian patients with chronic uveitis.

First detection of oxacillinase-mediated resistance to carbapenems in Klebsiella pneumoniae from Morocco.

The frequency of carbapenem resistance due to class-D beta-lactamases (i.e. oxacillinases) among the world's Enterobacteriaceae is increasing. Recently, in Morocco, two isolates of carbapenem-resistant Klebsiella pneumoniae were recovered from the same patient, one harbouring plasmid-encoded bla-(OXA-48) and the other the bla-(OXA-1) gene. This represents the first evidence of bla(OXA-48)-mediated carbapenem-resistance in Enterobacteriaceae in Morocco.

Eye and Behçet's disease.

Behçet's disease is a chronic multisystem disorder characterized by relapsing inflammation for which the underlying histopathology is an occlusive vasculitis. The disease has a high prevalence in the Mediterranean region, Far and Middle Eastern countries. It is clinically characterized by oral and genital ulcerations, ocular inflammatory involvement, skin lesions, vascular involvement and numerous other systemic manifestations. Uveitis is by far the most common ocular manifestation of Behçet's disease. It typically presents in the form of relapsing-remitting panuveitis with retinal vasculitis that may result in severe visual loss. Management of Behçet's uveitis relies on corticosteroid therapy, conventional immunosuppressive drugs and biological agents and requires a close collaboration between ophthalmologist and internist. A better understanding of auto-inflammatory process and of the role of cytokines implicated in the pathogenesis of Behçet's disease will enable researchers to develop more specific and effective therapy.

[Eye and Behçet's disease]. / Œil et maladie de Behçet.

Behçet's disease is a chronic multisystem disorder characterized by relapsing inflammation for which the underlying histopathology is an occlusive vasculitis. The disease has a high prevalence in the Mediterranean region, Far and Middle Eastern countries. It is clinically characterized by oral and genital ulcerations, ocular inflammatory involvement, skin lesions, vascular involvement and numerous other systemic manifestations. Uveitis is by far the most common ocular manifestation of Behçet's disease. It typically presents in the form of relapsing-remitting panuveitis with retinal vasculitis that may result in severe visual loss. Management of Behçet's uveitis relies on corticosteroid therapy, conventional immunosuppressive drugs and biological agents and requires a close collaboration between ophthalmologist and internist. A better understanding of the auto-inflammatory process and of the role of cytokines implicated in the pathogenesis of Behçet's disease will enable researchers to develop more specific and effective therapy.

[Idiopathic orbital inflammatory syndrome: Report of 24 cases]. / Syndrome d'inflammation orbitaire idiopathique : à propos de 24 cas.

BACKGROUND: Idiopathic orbital inflammatory syndrome (IOIS) is an inflammatory condition of unknown etiology. The inflammation may affect all the structures within the orbit (anterior, diffuse, apical, myositic, dacryoadenitis) and corresponds to uniquely orbital inflammation without an identifiable local cause or systemic disease. The goal of this study is to describe the clinical and radiographic characteristics of IOIS and discuss the role of orbital biopsy in this condition. PATIENTS AND METHODS: This is a retrospective review of the charts of 24 patients diagnosed with IOIS at Fattouma Bourguiba hospital, Monastir, Tunisia, from January 2007 to December 2015. This study included all patients with IOIS and a minimum follow-up of six months. All patients had a complete ophthalmological examination and orbital and head CT scan and/or MRI. A work-up was performed in all cases to rule out local causes and systemic disease. Only 11 patients underwent biopsy. The diagnosis of the clinical entity IOIS was made according to the Rootman criteria. Oral steroids were the first line therapy. A bolus of intravenous methylprednisolone was administered first in vision-threatening cases. Response to treatment was defined as disappearance of signs and symptoms of IOIS. RESULTS: Orbital pain was the most common symptom (62.5%), followed by proptosis and decreased vision (37.5% each). Best-corrected visual acuity (BCVA) was greater than 5/10 in 70.7% of patients. Lacrimal gland enlargement was observed in 3 patients. Oculomotor disorders were present in 70% of cases and 20.8% of patients had compressive optic neuropathy. Orbital imaging showed, in most cases, oculomotor muscle inflammation (87.5%) involving particularly the superior rectus muscle (54.2%) and inflammation of orbital fat (66.7%). Fifty percent had myositic inflammation. Biopsy was performed in 11 patients, showing nonspecific inflammation (n=10) and the sclerosing form (n=1). A total of 83.3% of patients received oral corticosteroids for a mean duration of 5.5 months. CONCLUSION: IOIS is a diagnosis of exclusion, based on history, clinical course, response to steroid therapy, laboratory tests, or even biopsy in selected cases. Orbital imaging provides valuable clues for diagnosis of IOIS and for identification of affected structures. Prolonged steroid therapy is necessary as IOIS classically responds to steroids; nevertheless, partial recovery or relapses often occur.

[Meningitis revealing Rickettsia typhi infection]. / Méningite révélant une infection à Rickettsia typhi.

INTRODUCTION: Neurological manifestations are rarely observed in murine typhus. We present a case of meningitis caused by Rickettsia typhi. EXEGESIS: We report a case of Tunisian 57-year-old woman admitted for suspicion of meningitis. Clinical examination revealed fever at 39,5 degrees C and nuchal rigidity. There were no focal neurologic signs, cutaneous rash or eschar. Lumbar puncture showed clear cerebrospinal fluid containing normal glucose, 0,48 g/l protein and 30 WBC (78% lymphocyte). Gram-stained smear and culture were negative. Serology confirmed the diagnosis. The patient was initially treated by ampicillin 12 g daily but remained febrile. Retinal lesions were detected on ophthalmic examination, suggesting rickettsial infection. Clinical outcome was good after 7-day treatment with oral ciprofloxacin 1,5 g daily. The mean follow-up was six months. CONCLUSION: Murine typhus is an endemic zoonosis. Neurological manifestations were uncommon. An ophthalmic examination is recommended if rickettsiosis was suspected.

[Incidence and causes of visual impairment in the district of Mahdia, in east Tunisia: Retrospective study of 1487 cases]. / Incidence et causes de déficiences visuelles au Gouvernorat de Mahdia, à l'est de la Tunisie : étude rétrospective à propos de 1487 cas.

OBJECTIVE: To study socio-demographic characteristics and main causes related to visual impairment (VI) as a function of age bracket and to analyze their trends over time in the district of Mahdia. METHOD: A retrospective review was performed on 1487 cases of visual impairment registered with the social authorities in Mahdia, between 1980 and 2013. The social, demographic, vision exam findings and causes were ascertained and analyzed in an SPSS database. Incidence rates of VI and blindness due to various causes were calculated based on the demographic data from the NSI to estimate the time trends using the general linear regression model and Spearman correlation. RESULTS: Analyses included 1487 participants with a median age of 47 years, 40.6% of cases were aged under 45 years. Children accounted for 11.1% (165 patients), while age was between 16 and 45 years in 29.5% (439 patients), between 46 and 65 years in 31.5% (469 patients) and greater than 65 years in 27.8% (414 patients). The sex-ratio (M/F) was 1.78. Socially, 51% came from rural areas, 62% were illiterate, and 84% were unemployed. We observed blindness in 70% of participants and low vision in 30%. In children, the causes were dominated by congenital cataract and congenital glaucoma, each present in 31 children (18.8%). Between 16 and 45 years, glaucoma and hereditary dystrophies of the retina were found in 62 and 61 patients respectively (14% each). For age between 46 and 65 years, trachoma was responsible for 19.8% of cases of VI, glaucoma in 15.8% and cataract in 15.1%. Beyond 65 years, glaucoma accounted for 30.7% of the causes of VI and cataract 27.8% of cases. Trend analysis shows a significant increase in the incidence rate of visual impairment with an average of 12% per year (P=0.001). The mean age increased by 46% (P=0.003). Trachoma increased by 118% (P<0.0001) between 1980 and 1990, then declined by 42% (P=0.0013) between 1991 and 2013. Incidence of VI significantly increased by 4% for cataract (P=0.001), 23% (P=0.001) for glaucoma and 20% (P=0.02) for diabetic retinopathy, while VI related to refractive errors and AMD showed no significant change. CONCLUSION: Advanced age, lower educational and socio-economic status were associated with bilateral VI. Age related eye problems are the main causes of VI, and their incidence is tending to increase. Public health policies and procedures should be targeted to risk related populations and age-related diseases in order to control the incidence of visual impairment and avoid its consequences.