Alagille Syndrome: A case report of a rare oral and multisystem manifestation

Alagille syndrome is an inherited multisystem disorder of autosomal dominant transmission. Its prevalence is estimated at 1 per 70,000 to 100,000 live births. We report the case of a young patient suffering from Alagille syndrome who consulted the center of diagnosis and dental treatment of Rabat - MOROCCO (CCTD). The general manifestations are facial dysmorphia, hepatic, cardiac, and ocular disorders. Hepatic cholestasis causes oral repercussions such as a yellow oral mucosa, hypomineralization of the teeth, and a high tendency to dental caries. The management of such a patient requires the knowledge of the general health of the patient, therefore collaboration with the attending physicians, the establishment of rigorous oral hygiene, personalized prophylaxis with a consequent contribution of fluorine.

Pattern of ocular Diseases among Children under Five Years of Age in Southeast, Nigeria

Background: Children under 5 years are prone to ocular disorders which could be congenital or acquired. Early recognition of these conditions and timely intervention enhances optimum results. There is paucity of data on the pattern of ocular disorders among these children in Nigeria and this makes it difficult for policy makers to plan health systems that will target this very important group of the population. Aim: To determine the pattern of ocular diseases among children less than 5 years of age in Onitsha, Anambra state Nigeria. Methods: This was a retrospective study of children under 5 years of age that presented to City of Refuge Specialist Eye Clinic Onitsha, Nigeria between January 1st, 2016 to December 31st, 2020. Their case files were retrieved and relevant information extracted. Sociodemographics, month of presentation to the eye clinic and diagnoses were analyzed. Results: A total of 133 children were studied. The patients comprised 85 (63.9%) males and 48 (36.1%) females, with an approximate male to female ratio of 1.8:1. Eye diseases seen were both congenital 32(24.1%) and acquired 101 (75.9%). Of the congenital type, 20 (62.5%) were males, while 12 (37.5%) were females. Most common ocular morbidities recorded were allergic conjunctivitis 41(30.8%) and infective conjunctivitis 34(25.6%). Conclusion: Most of the causes of ocular morbidity in this study were preventable or treatable. Therefore, early detection and management of eye diseases in children will reduce complications in later life.

A Rare Case of Dengue Fever with Abducens Nerve Palsy

Dengue fever is one of the most common vector borne disease which is a viral infection transmitted by aedes mosquito. Most common in the tropical countries. Neurological manifestations are not commonly seen in dengue, it can present as encephalitis, encephalopathy, neuromuscular disorders and neuro-ocular disorders. Cranial mononeuropathy is a very exceptional manifestation. A 48-year-old Indian male was diagnosed with dengue, complicated with isolated unilateral sixth cranial nerve palsy. The patient was managed conservatively. Patient made a fast and full ocular recovery following treatment with methyl prednisolone. Hence, dengue can present with a cranial nerve palsy and the recovery process can be hasten with the use of corticosteroids.

Pyroptosis: A New Insight Into Eye Disease Therapy

Pyroptosis is a lytic form of programmed cell death mediated by gasdermins (GSDMs) with pore-forming activity in response to certain exogenous and endogenous stimuli. The inflammasomes are intracellular multiprotein complexes consisting of pattern recognition receptors, an adaptor protein ASC (apoptosis speck-like protein), and caspase-1 and cause autocatalytic activation of caspase-1, which cleaves gasdermin D (GSDMD), inducing pyroptosis accompanied by cytokine release. In recent years, the pathogenic roles of inflammasomes and pyroptosis in multiple eye diseases, including keratitis, dry eyes, cataracts, glaucoma, uveitis, age-related macular degeneration, and diabetic retinopathy, have been continuously confirmed. Inhibiting inflammasome activation and abnormal pyroptosis in eyes generally attenuates inflammation and benefits prognosis. Therefore, insight into the pathogenesis underlying pyroptosis and inflammasome development in various types of eye diseases may provide new therapeutic strategies for ocular disorders. Inhibitors of pyroptosis, such as NLRP3, caspase-1, and GSDMD inhibitors, have been proven to be effective in many eye diseases. The purpose of this article is to illuminate the mechanism underlying inflammasome activation and pyroptosis and emphasize its crucial role in various ocular disorders. In addition, we review the application of pyroptosis modulators in eye diseases.

Ankle-brachial index and ocular diseases in a Russian population

Background To assess potential associations between the ankle-brachial blood pressure index (ABI) and ocular disorders. Methods In the population-based cross-sectional Russian Ural Eye and Medical Study including 5,899 (80.5%) out of 7328 eligible participants aged 40+ years, the participants underwent a series of ocular and medical examinations including measurement of ABI. Results Blood pressure measurements of both arms and ankles were available for 3187 (54.0%) individuals. The mean ABI was 1.26 ± 0.19 (median:1.20; range: 0.61, 2.20). In multivariate analysis, a higher ABI was associated with younger age (P < 0.001; non-standardized regression coefficient B: −0.001; 95% confidence interval (CI): −0.002, −0.001), female sex (P < 0.001; B: 0.03; 95% CI: 0.02, 0.04), lower body mass index (P < 0.001; B: −0.004; 95% CI: −0.006, −0.003), lower waist-to-hip ratio (P = 0.01; B: −0.10; 95% CI: −0.17, −0.02), lower glucose serum concentration (P = 0.008; B: −0.005; 95% CI: −0.009, −0.001), lower prevalence of arterial hypertension (P < 0.001; B: −0.14; 95% CI: −0.16, −0.12), higher mean systolic blood pressure (P < 0.001; B: 0.003; 95% CI: 0.002, 0.003), and higher prevalence of any alcohol consumption (P < 0.001; B: 0.03; 95% CI: 0.02, 0.04). In that multivariate model, prevalence of glaucoma (P = 0.67) as a whole, open-angle glaucoma (P = 0.86) and angle-closure glaucoma (P = 0.54), stage of glaucomatous optic neuropathy (P = 0.57), prevalence of age-related macular degeneration (P = 0.88), prevalence and stage of diabetic retinopathy (P = 0.30, and P = 0.29, respectively), nuclear cataract (P = 0.32, and P = 0.41, resp.), cortical cataract (P = 0.33, and P = 0.92, resp.), subcapsular cataract (P = 0.74 and P = 0.60, resp.), and pseudoexfoliation (P = 0.44 and P = 0.47, resp.), intraocular pressure (P = 0.52), axial length (P = 0.20), and peripapillary retinal nerve fibre layer thickness (P = 0.55) were not significantly associated with the ABI. Conclusions In this ethnically mixed population from Russia, none of the major ocular diseases was associated with ABI suggesting that subclinical atherosclerosis is not markedly associated with the aetiology of these ocular disorders.

Risk Mitigation of Immunogenicity: A Key to Personalized Retinal Gene Therapy

Gene therapy (GT) for ocular disorders has advanced the most among adeno-associated virus (AAV)-mediated therapies, with one product already approved in the market. The bank of retinal gene mutations carefully compiled over 30 years, the small retinal surface that does not require high clinical vector stocks, and the relatively immune-privileged environment of the eye explain such success. However, adverse effects due to AAV-delivery, though rare in the retina have led to the interruption of clinical trials. Risk mitigation, as the key to safe and efficient GT, has become the focus of ‘bedside-back-to-bench’ studies. Herein, we overview the inflammatory adverse events described in retinal GT trials and analyze which components of the retinal immunological environment might be the most involved in these immune responses, with a focus on the innate immune system composed of microglial surveillance. We consider the factors that can influence inflammation in the retina after GT such as viral sensors in the retinal tissue and CpG content in promoters or transgene sequences. Finally, we consider options to reduce the immunological risk, including dose, modified capsids or exclusion criteria for clinical trials. A better understanding and mitigation of immune risk factors inducing host immunity in AAV-mediated retinal GT is the key to achieving safe and efficient GT.

A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome

Mutations in the Forkhead Box C1 (FOXC1) are known to cause autosomal dominant hereditary Axenfeld-Rieger syndrome, which is a genetic disorder characterized by ocular and systemic features including glaucoma, variable dental defects, craniofacial dysmorphism and hearing loss. Due to late-onset of ocular disorders and lack of typical presentation, clinical diagnosis presents a huge challenge. In this study, we described a pathogenic in-frame variant in FOXC1 in one 5-year-old boy who is presented with hypertelorism, pupil deformation in both eyes, conductive hearing loss, and dental defects. By whole exome sequencing, we identified a 3 bp deletion in FOXC1, c.516_518delGCG (p.Arg173del) as the disease-causing variant, which was de novo and not detected in the parents, and could be classified as a “pathogenic variant” according to the American College of Medical Genetics and Genomics guidelines. After confirmation of this FOXC1 variant, clinical data on Axenfeld-Rieger syndrome-associated clinical features were collected and analyzed. Furthermore, Although the affected individual present hearing loss, however, the hearing loss is conductive and is reversible during the follow-up, which might not linke to the FOXC1 variant and is coincidental. Routine examination of FOXC1 is necessary for the genetic diagnosis of hypertelorism-associated syndrome. These findings may assist clinicians in reaching correct clinical and molecular diagnoses, and providing appropriate genetic counseling.

Applications of dynamic visual acuity test in clinical ophthalmology

Dynamic visual acuity test (DVAT) plays a key role in the assessment of vestibular function, the visual function of athletes, as well as various ocular diseases. As the visual pathways conducting dynamic and static signals are different, DVATs may have potential advantages over the traditional visual acuity tests commonly used, such as static visual acuity, contrast sensitivity, and static perimetry. Here, we provide a review of commonly applied DVATs and their several uses in clinical ophthalmology. These data indicate that the DVAT has its unique clinical significance in the evaluation of several ocular disorders.

Eye Disorders Spectrum: A Tertiary Hospital Pediatric Ophthalmology Clinic Based in Ethiopia

Background: Epidemiological studies to determine the pattern of eye disorders among children are important for proper health care planning and management. This study aimed to document the spectrum and frequency of eye diseases of children who attended the pediatric ophthalmology clinic of a tertiary teaching hospital Addis Ababa, Ethiopia. Methods: A cross sectional and convenient sample of 1237, male and female children (16 years and below) with ocular disorders presenting for the first time and those children with settled diagnosis coming for follow up visit between June 1, 2018 to May 31, 2019 were included in the study. Data on age at presentation, sex and diagnosis were collected and analyzed. Eye disorders were classified into various categories. Children were grouped into four age groups. Ratios, percentages and chi square associations were calculated. P< 0.05 was considered statistically significant.Results: Of the children 60% were male. The mean age (standard deviation) of the children was 4.26 (+4.1) years. Patients aged 0–5 years old were the largest group constituting 70.5%. Ocular motility imbalances were the most common ocular disorders seen (32.8 %), followed by childhood cataract (18.4%) and infection and inflammation of eye and adnexa (8.3%). Ocular motility imbalances were recorded more frequently and statistically significant (p < 0.001) among 1­ 5 years age group. Within the childhood cataract category, congenital cataract was more prominent (7.1%). Within the infection and inflammation category, cornea/ sclera infections were more common (3.7%). Conclusions: The study highlights common eye disorders seen in children in a specialized hospital ophthalmic clinic. Ocular motility imbalance, childhood cataract, and infection and inflammation of the eye and adnexa, were the most common occurring disorders. Early presentation was common, and males were more affected than females.