Oral Isotretinoin-Associated Ocular Effects and Risk Factors: A Cross-Sectional Study

Ismail I Abuallut,1 Mohammed Q Dibaji,2 Ahmad Assiri,3 Wedad Mawkili,4 Ahmed Y Najmi,5 Safa Abdu Ageeli,5 Amaal Abdulaziz Hamdi,5 Raum Abdu Ayoub,5 Abdulaziz Yahya Muyidi,5 Hussam T Hakami,5 Abrar Khalid Alhazmi,5 Moayad Hassan Rekini5 1Department of Surgery, Ophthalmology Division, Jazan University, Jazan, Saudi Arabia; 2Prince Mohammed Bin Nasser Hospital - Jazan Health cluster, Jazan, 82943, Saudi Arabia; 3Department of Dermatology, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia; 4Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan, Saudi Arabia; 5Faculty of Medicine, Jazan University, Jazan, Saudi ArabiaCorrespondence: Ismail I Abuallut, Ophthalmology Division, Jazan University, Jazan, Saudi Arabia, Email [email protected]: Oral isotretinoin is a derivative of vitamin A, used to treat acne vulgaris. One of its effects is altering the corneal surface and ocular glands, resulting in eye dryness and various other symptoms. This study aimed to analyze the impact of systemic isotretinoin treatment on ocular health and investigate the potential risk factors contributing to ocular pathology.Patients and Methods: This cross-sectional study was conducted on 489 participants in the Jazan region using a convenience sampling method. An online questionnaire composed of five sections, including the Arabic version of the validated Ocular Surface Disease Index (OSDI), was used to assess the presence of ocular symptoms associated with isotretinoin usage as well as the potential contributing risk factors.Results: A significant association was established between oral isotretinoin use and specific eye symptoms, including a gritty feeling in the eye (66.4%), sore eyes (68.6%), blurry vision (75.9%), and the need for moisturizing drops (35%). OSDI severity varied according to isotretinoin usage status, with severe OSDI grades reported in 56.9% of current users, 51.2% of those who stopped < 2 months ago, and 38.8% of those who stopped ≥ 2 months ago. Furthermore, significant risk factors associated with worse OSDI grades included contact lens use and isotretinoin dose, with contact lens use being associated with a 17.5-point increase in OSDI scores, while each 10 mg increase in isotretinoin dose was linked to a 0.20-point rise in OSDI score.Conclusion: This study emphasizes the importance of assessing individual risk factors before starting isotretinoin therapy and monitoring ocular health in patients undergoing therapy. Clinicians should be aware of preventive methods and should consider high-risk patients to an ophthalmologist for interventions, such as punctal plugs, that can reduce complications. Further research targeting specific populations with shared risk factors is needed to validate these findings.Keywords: retinoids, ocular pathology, eye dryness, Saudi Arabi

Myhre and LAPS syndromes: Clinical and molecular review of 32 patients

Myhre syndrome is characterized by short stature, brachydactyly, facial features, pseudomuscular hypertrophy, joint limitation and hearing loss. We identified SMAD4 mutations as the cause of Myhre syndrome. SMAD4 mutations have also been identified in laryngotracheal stenosis, arthropathy, prognathism and short stature syndrome (LAPS). This study aimed to review the features of Myhre and LAPS patients to define the clinical spectrum of SMAD4 mutations. We included 17 females and 15 males ranging in age from 8 to 48 years. Thirty were diagnosed with Myhre syndrome and two with LAPS. SMAD4 coding sequence was analyzed by Sanger sequencing. Clinical and radiological features were collected from a questionnaire completed by the referring physicians. All patients displayed a typical facial gestalt, thickened skin, joint limitation and muscular pseudohypertrophy. Growth retardation was common (68.7%) and was variable in severity (from -5.5 to -2 SD), as was mild-to-moderate intellectual deficiency (87.5%) with additional behavioral problems in 56.2% of the patients. Significant health concerns like obesity, arterial hypertension, bronchopulmonary insufficiency, laryngotracheal stenosis, pericarditis and early death occurred in four. Twenty-nine patients had a de novo heterozygous SMAD4 mutation, including both patients with LAPS. In 27 cases mutation affected Ile500 and in two cases Arg496. The three patients without SMAD4 mutations had typical findings of Myhre syndrome. Myhre-LAPS syndrome is a clinically homogenous condition with life threatening complications in the course of the disease. Our identification of SMAD4 mutations in 29/32 cases confirms that SMAD4 is the major gene responsible for Myhre syndrome