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).

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.

Unusual cause of cerebral calcifications in an 8-year-old girl.

Key Clinical Message: Genetic counseling and genetic screening for hyperoxaluria should be recommended for children with urinary lithiasis for early management to avoid progression to oxalosis especially if there is a family history of lithiasis.Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT) resulting in overproduction of calcium oxalates. In its later stage, a systemic deposit of calcium oxalates is observed. We present the case of an 8-year-old girl with exceptional neurological involvement secondary to this disease.

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.

Primary hyperoxaluria type 1: Clinical, genetic, and evolutionary characteristics in Tunisian children.

INTRODUCTION: There are three types of primary hyperoxaluria, with type 1 considered the most severe. AIM: To analyze the clinical, genetic, and evolutionary characteristics of type 1 primary hyperoxaluria with pediatric onset. METHODS: This was a retrospective, descriptive study that included Tunisian children under the age of 18 at the time of diagnosis over a period of 25 years (January 1, 1996, to December 31, 2022). RESULTS: Thirty-five patients were included, with a mean age of 4.1 years. The most common presenting circumstances of the disease were nephrolithiasis and end-stage renal failure. The average serum creatinine level was 225.42 µmol/l. Five mutations were identified, with the p.Ile244Thr mutation being the most prevalent. Nephrocalcinosis, surgical intervention, and a creatinine level ≥57 µmol/l were predictive of progression to end-stage renal failure. The infantile form was predictive of mortality. CONCLUSIONS: Screening for the disease would improve the prognosis of this condition.

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.

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.

Contribution of ultra-wide field fluorescein angiography in diabetic retinopathy in a Tunisian population.

AIM: To assess the contribution of ultra-wide field (UWF) fluorescein angiography (FA) in clinically non proliferative diabetic retinopathy (DR) and to study the relationship between peripheral vascular lesions and the presence of diabetic macular edema (DME). METHODS: Retrospective study of consecutive UWF-FA obtained using a wide-field contact lens system. DME was detected on both FA and spectral-domain optical coherence tomography (SD-OCT). RESULTS: A total of 71 eyes of 39 diabetic patients with clinically non proliferative DR (NPDR) was included. DR was clinically graded as severe NPDR in 52 eyes (73%), moderate NPDR in 15 eyes (21%) and mild NPDR in 4 eyes (6%). On UWF-FA, DR was predominantly anterior in 14% of cases (10/71), predominantly posterior in 48% of cases (34/71) and diffuse in 38% of cases (27/71). Retinal non perfusion was present in 87% of eyes (62/71), predominating in superior-temporal areas. Peripheral vessel leakage was present in 85% of cases (60/71) and retinal neovascularization was noted in 14% of cases (10/71), unpgrading DR severity from NPDR to proliferative DR in 10 eyes. DME was present on SD-OCT in 53% of cases. Central macular thickness was significantly higher in eyes with retinal non-perfusion (353 µm vs. 254 µm, p=0,006) and retinal non-perfusion was associated with macular edema (97% vs. 76%, p=0,01) and poor visual acuity (p<0.001). Peripheral vessel leakage was associated with retinal non-perfusion (p<0.001) and retinal neovascularization (53% vs. 35%, p=0.01), but it was not associated with the presence of DME (p=0.449). CONCLUSION: UWF-FA was of great help assessing DR and evaluating peripheral retinal lesions in order to refine DR staging and to guide laser treatment. Besides, it allows better understanding of DME pathophysiology.

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.

Spectral Domain optical coherence tomography findings in patients with retinitis pigmentosa.

Background Maculopathy is a common complication of retinitis pigmentosa (RP), and compromise the visual acuity of RP patients even in the less advanced stages. Aim To report the morphological macular findings detected by spectral domain optical coherence tomography (SD-OCT) and to determine their prevalence in patients with retinitis pigmentosa (RP). Methods  SD-OCT scans from 100 patients (196 eyes) affected by RP were reviewed. Results We noted a normal macula appearance in 48.5%, macular edema in 14.5% and macular atrophy in 37%. Mean central macular thickness was 167.79 microns and we did not note any statistically significant correlation between visual acuity and foveal thickness. Visual acuity was statistically better in eyes with a larger number of hyper-reflective layers (p<0.001) and in eyes with photoreceptor inner/outer (IS/OS) segment junction distinct (p<0.001). We have identified three types of tomographic macular edema: a cystoids macular edema in 6.8%, a tractional edema in 8.2% and mixed edema in 1%. We identified two tomographic types of macular atrophy: a central- foveal atrophy in 34 eyes (11.6%) and diffuse atrophy in 38 eyes (12.9%). Epiretinal membrane was present in 24 eyes (8.2%). Conclusions The OCT contributes to the analysis of epidemiological and morphological of different macular involvement in RP. OCT has a prognostic value, which essentially depends on the morphology of the IS/OS line and number of hyper-reflective layers.