Absent meibomian glands and cone dystrophy in ADULT syndrome: identification by whole exome sequencing of pathogenic variants in two causal genes TP63 and CNGB3.

BACKGROUND: Ectrodactyly is a rare congenital limb malformation characterized by a deep median cleft of the hand and/or foot due to the absence of central rays. It could be isolated or depicts a part of diverse syndromic forms. Heterozygous pathogenic variants in the TP63 gene are responsible for at least four rare syndromic human disorders associated with ectrodactyly. Among them, ADULT (Acro-Dermato-Ungual-Lacrimal-Tooth) syndrome is characterized by ectodermal dysplasia, excessive freckling, nail dysplasia, and lacrimal duct obstruction, in addition to ectrodactyly and/or syndactyly. Ophthalmic findings are very common in TP63-related disorders, consisting mainly of lacrimal duct hypoplasia. Absent meibomian glands have also been well documented in EEC3 (Ectrodactyly Ectodermal dysplasia Cleft lip/palate) syndrome but not in ADULT syndrome. METHODS: We report a case of syndromic ectrodactyly consistent with ADULT syndrome, with an additional ophthalmic manifestation of agenesis of meibomian glands. The proband, as well as her elder sister, presented with congenital cone dystrophy.The molecular investigation was performed in the proband using Whole Exome Sequencing. Family segregation of the identified variants was confirmed by Sanger sequencing. RESULTS: Two clinically relevant variants were found in the proband: the novel de novo heterozygous missense c.931A > G (p.Ser311Gly) in the TP63 gene classified as pathogenic, and the homozygous nonsense pathogenic c.1810C > T (p.Arg604Ter) in the CNGB3 gene. The same homozygous CNGB3 variation was also found in the sister, explaining the cone dystrophy in both cases. CONCLUSIONS: Whole Exome Sequencing allowed dual molecular diagnoses: de novo TP63-related syndromic ectrodactyly and familial CNGB3-related congenital cone dystrophy.

Clinical features of infectious uveitis in a Tunisian population.

INTRODUCTION: Infectious uveitis (IU), one of the main causes of ocular inflammation in Tunisia, has various etiologies and clinical presentations. AIM: To report the causes and clinical features of IU in a Tunisian population. METHODS: Patients with IU referred to our department from February 2019 to January 2022 were included in a retrospective observational study. Ophthalmic examination and appropriate ancillary tests were performed. RESULTS: Eighty eyes of 63 patients were included (37 female and 26 male). The mean age was 45 years. IU was unilateral in 43 cases, bilateral in 17, and unilateral alternating in three cases. Panuveitis was the most common anatomic location (35% of cases) followed by posterior (31%), anterior (18 eyes), intermediate (6 eyes) and anterior and intermediate uveitis (3 eyes). Non granulomatous uveitis (55%) occurred more frequently than granulomatous uveitis (45%). Etiologies were dominated by bacterial infections (29 patients; 46%), mainly tuberculosis (23 patients), followed by viruses (19 patients), mainly Herpes simplex virus. Fungal infection was found in one patient, while parasites accounted for 14 cases, mostly toxoplasmosis. Mean initial diagnostic delay was 16 months. The most common complications included occlusive retinal vasculitis (19 eyes), cataract (17 eyes), cystoid macular edema (17 eyes) and papilledema (15 eyes). CONCLUSION: This study highlighted the causes and clinical features of IU in our setting. Tuberculosis remains one of its most frequent etiologies in Tunisia. However, a larger multicenter national study would allow a more precise evaluation.

Peripheral retinal cysts in presumed ocular toxocariasis.

Typical clinical manifestations of ocular toxocariasis are central posterior granuloma, peripheral granuloma and chronic endophthalmitis. Herein we report the presence of peripheral subretinal cysts in two cases with a presumed ocular toxocariasis (OT).

Ocular Manifestations After Acute Methanol Poisoning.

Acute methanol poisoning is first and foremost life-threatening. Otherwise, functional prognosis is mainly based on ocular impairment. In this case series we aimed to describe the ocular manifestations after acute methanol poisoning during an outbreak in Tunisia. The data from 21 patients (41 eyes) were analysed. All patients underwent a complete ophthalmological examination including visual fields, colour vision test and optical coherence tomography with evaluation of the retinal nerve fibre layer. Patients were classified into two groups. Group 1 included patients with visual symptoms and group 2 included patients with no visual symptoms. Ocular abnormalities were seen in 81.8% of patients with ocular symptoms. They included: optic neuropathy in 7 patients (63.6%); central retinal artery occlusion in 1 patient (9.1%); and central serous chorioretinopathy in 1 patient (9.1%). Mean blood methanol levels were significantly higher in patients without ocular symptoms (p = .03).

Neuro-Ophthalmological Manifestations of Horner's Syndrome: Current Perspectives.

Horner's syndrome (HS) is caused by a damage to the oculosympathetic pathway. HS may be congenital, but it is usually acquired and may reveal a life-threatening condition. According to the anatomic location of the underlying pathologic process, HS is classified as central, pre- or postganglionic, when the lesion affects the first, second or third-order neuron, respectively. Pharmacological testing, if available, can be used to differentiate HS from « pseudo-HS ¼ in patients with mild symptoms. Given the financial burden that imaging of the entire oculosympathetic pathway represents, a targeted imaging approach is advised. Although in the majority of cases, clinical examination may predict etiology, in other cases pharmacological testing can help in the localization process. We searched PubMed data base for papers published before December 2022 that concerned Horner's syndrome, its neuro-ophthalmological manifestations and diagnosis. In this article, we describe the main neuro-ophthalmological manifestations of the three types of HS, the most common etiologies, and a targeted diagnostic strategy in each type.

Surgical management of lifebuoy cataract.

Lifebuoy cataract is a rare form of congenital cataract with anatomical characteristics. Herein, we present a case of an otherwise healthy 42-year-old female with a long-standing history of blurred vision. Examination showed the presence of esotropia and bilateral horizontal nystagmus. Visual acuity was limited to light perception in both eyes. Slit-lamp examination showed a calcified lens capsule with the absence of lens material in the right eye and the presence of an annular cataract in the left eye, corresponding to a unilateral lifebuoy cataract. She underwent cataract surgery with intraocular lens implantation. We report the clinical findings, anterior segment optical coherence tomography (AS-OCT), and surgical management tips. We noticed that during surgery, both anterior capsulorhexis and central membrane removal were the most challenging steps due to the absence of central nucleus and the strong adherence of central membrane to the anterior hyaloid.

A novel WFS1 variant associated with severe diabetic retinopathy in Wolfram syndrome type 1.

BACKGROUND: Wolfram syndrome type 1 is a rare neurodegenerative disorder including diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, with variable additional findings. The phenotypic spectrum is very heterogeneous, with non-autoimmune juvenile-onset diabetes and optic atrophy as minimal criteria for the diagnosis. Biallelic mutations in the WFS1 gene are the causative genetic anomaly for the syndrome, with, however, no evident genotype-phenotype correlation. Among the clinical features of the disease, diabetic retinopathy depicts a rarely reported microvascular complication. In this report, we describe the clinical and genetic findings in a 26-year-old patient presenting with Wolfram syndrome and severe diabetic retinopathy. METHODS: The mutation screening was performed by polymerase chain reaction followed by Sanger sequencing of the entire coding sequence of the WFS1 gene. RESULTS: A novel homozygous missense variant c.1901A>T (p.Lys634Met) was found in the proband and classified as probably pathogenic according to the American College of Medical Genetics and Genomics. CONCLUSIONS: The molecular study of the WFS1 gene is essential for the diagnostic confirmation, to provide appropriate genetic counseling and a mutational screening in the at-risk relatives. The c.1901A>T (p.Lys634 Met) is a novel variant that could be responsible for a severe form of Wolfram syndrome with early and proliferative diabetic retinopathy.

A Case of Infantile Cataract and Neonatal Hypoglycemia.

Purpose: To describe a case of lamellar cataract in a child with a history of neonatal hypoglycemia and illustrate the importance of meticulous history-taking in children with cataracts, especially before planning surgery. Methods: A single case report. Results: A 7-year-old girl with a history of neonatal hypoglycemia and ketoacidosis with high suspicion of a primary defect in ketone body utilization who presented with bilateral progressive blurred vision. Her best-corrected visual acuity (BCVA) was 20/200 in her right eye (OD) and 20/400 in her left eye (OS). Slit-lamp examination showed the presence of bilateral dense lamellar cataract. Fundus examination was unremarkable in both eyes (OU). She underwent cataract surgery with intraocular lens implantation under general anesthesia without prolonged fasting. Final BCVA was 20/82 in OD and 20/63 in OS. Conclusion: Our aim through this case is to emphasize the importance to screen for episodes of hypoglycemic attacks in children with infantile cataracts.

Attitudes of ophthalmologists towards pharmaceutical promotion.

INTRODUCTION: The interaction between physicians and pharmaceutical industry highlighted many issues lately concerning their influence on physician's attitude and their prescribing behavior. AIM: To evaluate the attitudes of Tunisian ophthalmologist towards pharmaceutical promotion. METHODS: Data was collected through an auto-administered anonymous questionnaire elaborated in French that was distributed to 160 ophthalmologists (residents and specialists) working in hospitals or private practices in four Tunisian governorates (Tunis, Sousse, Monastir and Sfax). RESULTS: One hundred and two valid responses were received. Twenty-nine respondents (28.43%) estimated the number of visits by pharmaceutical representatives (PR) at 11 to 20 times during the last year. Most physicians considered guides (94%), drug samples (88%), articles (86%), stationery (81%), sponsorship of overseas conferences (72%) and international trips to symposia organized by pharmaceutical industries (58%), as appropriate gifts. Over 80% of doctors agreed that promotional activities by drug companies were appropriate. Accepting sponsorship from a pharmaceutical company for a partner to attend a meeting was considered inappropriate by 79% of ophthalmologists. Eighty-eight percent of the respondents agreed that receiving gifts will increase their prescription of the company's drug. However, they perceived themselves to be less influenced than their colleagues (p=0.011). Eighty-six percent of ophthalmologists reported training about how to interact with PR to be insufficient. CONCLUSIONS: Despite the role of PR in supporting research, ethical issues may arise through their interactions with healthcare professionals. Training about pharmaceutical promotion and appropriate ways to deal with it are lacking in Tunisian medical schools' curricula, leaving future doctors unprepared to deal with pharmaceutical influences.

Acute Painful Horner's Syndrome Revealing Eagle's Syndrome: A Report of Two Cases.

Eagle's syndrome (ES) is characterised by an abnormally elongated styloid process. It remains a complex pathology and the ophthalmological symptoms are relatively rare. Herein, we report two cases who presented to our clinic with unilateral and painful Horner's syndrome. Computed tomography scanning showed the presence of ES with unilateral extrinsic compression of the sympathetic plexus by the styloid.

Posterior Microphthalmos Pigmentary Retinopathy Syndrome with Angle-Closure Glaucoma: A Case Report.

Purpose: To describe a particular form of posterior microphthalmos pigmentary retinopathy syndrome (PMPRS) with an atypical clinical presentation of pigment retinal dystrophy and an association to an inconstant complication which is angle-closure glaucoma (ACG). Methods: A 40-year-old male patient with ACG on maximal topical treatment was referred to our department for uncontrolled intraocular pressure. Best-corrected visual acuity was 2/10 in the right eye and light perception in the left eye. Intraocular pressure was 36 mmHg bilaterally. He had 360° peripheral anterior synechiae on gonioscopy. Fundus examination revealed total cupping with pale retinal lesions in both eyes and a few pigment deposits in the midperiphery of the right eye. Multimodal imaging was done. Results: Fundus autofluorescence revealed patchy areas of hypoautofluorescence. Optical coherence tomography (OCT) showed bilateral foveoschisis and macular folds. Anterior segment OCT showed a circumferential iridocorneal angle closure. Axial length measured with ultrasound biomicroscopy was 18.4 mm in the right eye and 18.1 in the left eye. Electroretinogram revealed attenuated scotopic responses. The patient was diagnosed with nanophthalmos-retinitis pigmentosa (RP)-foveoschisis syndrome complicated with ACG. A combined surgery with phacoemulsification - anterior vitrectomy - intraocular lens implantation and trabeculectomy was performed in both eyes with a satisfactory outcome. Conclusions: In its typical forms, PMPR syndrome is an association of nanophthalmos - RP - foveoschisis and optic nerve head (ONH) drusen. Incomplete phenotypes may lack ONH drusen or foveoschisis. Patients with PMPRS have to be screened for iridocorneal angle synechia and ACG.

Optical Coherence Tomography Angiography in idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) syndrome: A case report.

PURPOSE: Since its first description by Chang et al. in 1995, the diagnosis of Idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) syndrome has been based on the findings of Fundus Fluorescein Angiography (FFA). Our purpose was to describe the utility of optical coherence tomography angiography (OCT-A) in its diagnosis and management. CASE DESCRIPTION: A 40-year-old female presented with bilateral blurred vision. Her best corrected visual acuity was at 8/10. Fundus examination revealed blurred disc margins, perivascular exudates, arterial sheaths and retinal hemorrhages bilaterally. FFA showed staining of the optic disc with dye leakage in the right eye, a punctuate hyperfluorescence of the temporosuperior artery in the left eye, bilateral vascular sheathing and capillary dropout. OCT-A showed simultaneous presence of papillary aneurysm and neovascularization of the optic nerve head in the right eye, a papillary aneurysm in the left eye and bilateral capillary non-perfusion. Our patient was diagnosed with IRVAN syndrome. Oral steroids associated with panretinal laser photocoagulation and intravitreal injection of bevacizumab in the right eye resulted in vanishing of the papillary neovascularization with no recurrence on OCT-A at 10-month follow-up. CONCLUSIONS: OCT-A is an additional tool to FFA for visualization of arterial macroaneurysms and retinal neovascularization without the interference of dye leakage. It well demarcates nonperfused areas and ensures follow-up of retinal neovascularization. Its limitations are the limited field of view and the low sensitivity in detecting arteriolar dilations. Thus, OCT-A is unable to outplace FFA but should be considered alternately with it for non-invasive follow-up of IRVAN syndrome.

Epidemiological, clinical, and therapeutic characteristics of Behçet's disease: a monocentric study in Tunisia.

INTRODUCTION: to describe the epidemiological, clinical, therapeutic and evolving characteristics of Behçet´s disease and identify prognostic factors. METHODS: we have realized a retrospective, single-center study, conducted over a period of 26 years and including 130 patients presenting Behçet´s disease and hospitalized in an Internal Medicine Department. RESULTS: the mean age of the Behçet´s disease at onset was 30.3 ±8.8 years and that at diagnosis was 34.6 ±9.4 years. The sex ratio (male/female) was 2.5. The mean delay of diagnosis was 53.5 months. Oral aphthosis was constant. The frequency of the manifestations was: genital aphtosis 71.5%, pseudofolliculitis 84.6%, erythema nodosum 11.5%, positive pathergy test 50%, ocular disease 36.9%, venous thrombosis 30%, arterial disease 4.6%, joint damage 30.8%, neurological disease 19.2% and digestive disease 0.8%. The male gender was significantly associated with ocular involvement (p =0.02), venous disease (p =0.01) and occurrence of relapses (p =0.01). The mean follow up was 68.5 ± 77.3 months. The poor survival prognostic factors were male gender, ocular involvement, venous disease, cardiovascular disease, a duration of follow up ≤12 months and a diagnostic delay ≤ 24 months. Conclusion: improving the prognosis of Behçet´s disease requires a shortening of the time to diagnosis, multidisciplinary collaboration, intensive treatment of functional threats, regular monitoring, and patient adherence.

Swept Source OCT in monitoring uveal effusion after trabeculectomy in a nanophtalmic eye.

Uveal effusion syndrome describes serous detachments of the choroid and ciliary body with exudative retinal detachment. It is a complication following glaucoma filtering surgeries such as trabeculectomy especially in nanophthalmic eyes. We report a rare case of a 42-year-old-woman, with nanophtalmos, who developed posterior serous retinal detachment and uveal effusions after trabeculectomy for chronic angle closure glaucoma. The patient was put on oral steroids with good clinical outcome. Anterior Segment OCT allowed monitoring of iridocorneal angle and anterior chamber depth, Swept Source OCT was useful for monitoring retinal reattachment and choroidal thickness.

Quantitative Analysis of Microvascular Network with Optical Coherence Tomography Angiography and its Correlation with Visual Acuity in Retinal Vein Occlusion.

PURPOSE: To analyze the macular microvascular network and the correlations between visual acuity and quantitative parameters using optical coherence tomography angiography (OCTA) in eyes with retinal vein occlusion (RVO). METHODS: We conducted a prospective cross-sectional study including patients with unilateral RVO. We performed 4.5 mm × 4.5 mm macular OCTA angiograms for assessment of quantitative parameters in both superficial and deep capillary plexuses (SCP, DCP). Area of foveal avascular zone (FAZ), vascular density (VD), skeleton density (SD), fractal dimension (FD), vessel diameter index (VDI), and lacunarity (LAC) were analyzed. RESULTS: Seventy eyes of 35 patients were enrolled. As compared to fellow eyes, OCTA analysis in eyes with RVO showed larger FAZ, lower VD, lower SD, lower FD, higher VDI, and increased LAC in both plexuses (All P < 0.05). The enlargement of FAZ in the SCP was associated with visual loss (P = 0.025, r = 0.378). In the DCP, visual acuity was negatively correlated with parafoveal VD, SD, and FD (P = 0.004, r = -0.472; P = 0.003, r = -0.482 and P = 0.036, r = -0.308, respectively). Stepwise multivariate regression analysis showed that lower SD and lower FD in the DCP remained correlated with poorer visual acuity (P = 0.04, r = -0.261 and P = 0.032, r = -0.264, respectively). CONCLUSIONS: OCTA provides quantitative parameters to analyze retinal microvasculature in eyes with RVO. These OCTA biomarkers could be used to predict the impact of macular ischemia and capillary dropout on visual acuity in RVO.

Granular type I corneal dystrophy in a large consanguineous Tunisian family with homozygous p.R124S mutation in the TGFBI gene.

Purpose: We report the clinical features and the mutational analysis in a large Tunisian family with granular corneal dystrophy type I (GCD1). Patients and Methods: Thirty-three members of the Tunisian family underwent a complete ophthalmologic examination. DNA extraction and direct Sanger sequencing of the exons 4 and 12 of transforming growth factor ß Induced (TGFBI) gene was performed for 42 members. For the molecular modeling of TGFBI protein, we used pGenTHREADER method to identify templates, 3D-EXPRESSO program to align sequences, MODELLER to get a homology model for the FAS1 (fasciclin-like) domains and finally NOMAD-ref web server for the energy minimization. Results: The diagnosis of GCD1 was clinically and genetically confirmed. Sequencing of exon 4 of TGFBI gene revealed the p.[R124S] mutation at heterozygous and homozygous states in patients with different clinical severities. Visual acuity was severely affected in the homozygous patients leading to a first penetrating keratoplasty. Recurrence occurred rapidly, began in the seat of the corneal stitches and remained superficial up to 40 years after the graft. For heterozygous cases, visual acuity ranged from 6/10 to 10/10. Corneal opacities were deeper and predominating in the stromal center. According to bioinformatic analysis, this mutation likely perturbs the protein physicochemical properties and reduces its solubility without structural modification. Conclusions: Our study describes for the first time phenotype-genotype correlation in a large Tunisian family with GCDI and illustrates for the first time clinical and histopathological presentation of homozygous p.[R124S] mutation. These results help to understand pathophysiology of the disease.

Ischemic cardiomyopathy revealed by central retinal artery occlusion (CRAO).

Here we report a case of central retinal artery occlusion revealing an ischemic cardiomyopathy. A 54-year old smoker man presented at the hospital because of sudden visual loss in his left eye. There was cherry-red spot in the macula in his left eye. We performed a fluorescein angiogram and cervical color Doppler. Later investigations revealed an ischemic cardiomyopathy undiagnosed until then.