Nusinersen Treatment for Spinal Muscular Atrophy: Retrospective Multicenter Study of Pediatric and Adult Patients in Kuwait.

Spinal muscular atrophy is a neuromuscular genetic condition associated with progressive muscle weakness and atrophy. Nusinersen is an antisense oligonucleotide therapy approved for the treatment of 5q spinal muscular atrophy in pediatric and adult patients. The objective of this clinical case series is to describe the efficacy and safety of nusinersen in treating spinal muscular atrophy in 20 pediatric and 18 adult patients across six treatment centers in Kuwait. Functional motor assessments (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders, Hammersmith Functional Motor Scale Expanded, and Revised Upper Limb Module) were used to assess changes in motor function following nusinersen treatment. The safety assessment involved clinical monitoring of adverse events. The results demonstrate clinically meaningful or considerable improvement in motor performance for nearly all patients, lasting over 4 years in some cases. A total of 70% of patients in the pediatric cohort and 72% of patients in the adult cohort achieved a clinically meaningful improvement in motor function following nusinersen treatment. Additionally, nusinersen was well-tolerated in both cohorts. These findings add to the growing body of evidence relating to the clinical efficacy and safety of nusinersen.

Quality of life improvement in dry eye patients after intense pulsed light therapy compared to punctal plugs.

PURPOSE: The purpose of the study was to evaluate the quality of life (QOL) improvement in evaporative dry eye patients after treatment with intense pulsed light (IPL) therapy compared to punctal plug insertion. METHODS: A prospective comparative interventional study included 30 patients with moderate-to-severe evaporative dry eye. Patients' QOL affection before and after treatment was assessed by the Ocular Surface Disease Index (OSDI) questionnaire. Fifteen patients were treated with IPL therapy (Group 1). The other 15 patients were treated with silicone punctal plug insertion (Group 2). RESULTS: Improvement of patients' QOL was noticed in all patients of Group 1, with significant improvement of OSDI score from a mean value of 56.9 to 22.9 (P = 0.001). Improvement was noticed in 80% of Group 2 patients (mean OSDI score pretreatment: 53.8 and posttreatment: 31.7, P = 0.017). The tear breakup time (TBUT) in Group 1 significantly improved from a mean of 3.2 s to 5.9 s (P = 0.001), whereas it showed no significant changes in Group 2 (mean TBUT pretreatment: 3.6 s and posttreatment: 3.9 s, P = 0.654). Complications occurred in 13.3% in Group 2, including punctal granuloma and proximal canalicular obstruction. No adverse effects were recorded in Group 1. CONCLUSION: IPL therapy had better results with more improvement of patients' QOL compared to punctal plugs. It also showed a better safety profile with no reported complications.

Clinical and dermoscopic assessment of ablative carbon dioxide laser versus intradermal heparin sodium in xanthelasma.

BACKGROUND: Ablative carbon dioxide (CO2 ) laser is still a cornerstone in the management of xanthelasma. However, post-laser complications such as post-inflammatory hyperpigmentation or scarring have to be considered. Heparin sodium was recently suggested as an effective therapeutic modality for xanthelasma. OBJECTIVE: The aim of this work was to compare the therapeutic value of ablative CO2 laser versus intradermal heparin sodium in xanthelasma. METHODS: This study was piloted on 30 xanthelasma patients, whose lesions were randomly categorized into two groups. Group A was managed with CO2 laser ablation (2 sessions scheduled every 4 weeks), whereas Group B was managed with intradermal heparin sodium injections (10 sessions scheduled every week). Pre- and post-treatments evaluations were done both clinically and dermoscopically. RESULTS: Significant reduction of xanthelasma lesions was reported in response to both therapeutic interventions. However, the ablative CO2 laser was more significantly effective than intradermal heparin sodium. Interestingly, intradermal injection of heparin sodium was nearly as effective as ablative CO2 laser in early (<2 years duration) grade I and II xanthelasma, with a lower incidence of post-therapy side effects. CONCLUSIONS: Intradermal injection of heparin sodium could be suggested as a safe and cost-effective therapeutic technique for early mild grade I and II xanthelasma. Moreover, it could be recommended as a pre-operative management of grade III and IV xanthelasma to reduce the lesions to be easily ablated with CO2 laser.

A new treatment modality for the enlarged extraocular muscles.

PURPOSE: evaluation of the role of combined injection of triamcinolone acetonide with 5 Fluorouracil in treatment of the enlarged extraocular muscles secondary to chronic non-specific non-infectious inflammation. METHODS: injection of 0.1 ml of triamcinolone acetonide 40 mg/ml and 0.1 ml of 5 Fluorouracil 50 mg/ml in the enlarged extraocular muscles secondary to chronic non-specific non-infectious inflammation in 6 patients, after the confirmation of the histopathological diagnosis of these patients by revising their medical records. RESULTS: There was a significant improvement in the visual acuity, in addition to a significant improvement also in the clinical and the radiological features in the patients who were consented for the trial of the new injection protocol. However, there was failure of clinical and radiological improvement in one case presented with sever fibrosis. There was a significant absence of the side effects in all patients except for one patient that reported discomfort near the inner canthus. CONCLUSION: The new protocol of the treatment is a promising modality that can be used in the chronic non-infectious inflammation without extensive fibrosis.

Role of muscle biopsy in diagnosis of extraocular muscles enlargement.

PURPOSE: To study the role of muscle biopsy in patients with enlarged extraocular muscles. METHODS: A retrospective review of 31 patients who underwent biopsy for extraocular muscle enlargement. Characteristics, including signs, symptoms, imaging findings, and histopathological assessment were examined. RESULTS: Chronic inflammatory disorders represented the most common cause of the muscle enlargement followed by malignancy/metastasis. Multiple muscle involvement was more consistent with benign diseases, whereas single muscle involvement was more consistent with malignant causes. Positive predictive value of muscle biopsy was 0.52 for determining a specific cause of the muscle enlargement. CONCLUSIONS: Muscle biopsy is the standard for diagnosis in patients with extraocular muscle enlargement. This diagnostic test should be performed in every case of non-resolving muscle enlargement, with a specific diagnosis being made in over half of cases.

Evaluation of plasma exeresis as a new technique for non surgical treatment of dermatochalasis.

BACKGROUND: Dermatochalasis is frequently associated with tissue ageing and leads to multiple functional and cosmetic issues. There are several possible medical and surgical treatments available, such as blepharoplasty and laser therapy. OBJECTIVE: The aim of this work was to evaluate plasma exeresis as a new technique for nonsurgical treatment of dermatochalasis of the upper eyelid. PATIENT AND METHODS: This clinical trial included 40 female patients with dermatochalasis. Each patient received 3 sessions of treatment with the technology of plasma exeresis with one-month interval. Final evaluation was performed three months after the last session by 2 blinded dermatologists and 2 ophthalmologists, lid laxity according to facial laxity rating scale (FLRS), marginal crease distance (MCD) before and after treatment and patient satisfaction score. RESULTS: There was a significant decrease in eye lid laxity (FLRS) after treatment where p < .001; 36 (90%) patients had change and 4 (10%) patients without change in general. There was a significant increase in MCD after treatment (p = .001). CONCLUSION: Plasma exeresis seems to improve appearance of the upper eyelid, without any serious adverse events and could be a valid solution for dermatochalasis especially in mild and moderate cases.

Biotin-thiamine responsive basal ganglia disease in the era of COVID-19 outbreak diagnosis not to be missed: A case report.

BACKGROUND: Biotin-thiamine-responsive basal ganglia disease (BTRBGD) is a rare treatable autosomal recessive neurometabolic disorder characterized by progressive encephalopathy that eventually leads to severe disability and death if not treated with biotin and thiamine. BTRBGD is caused by mutations in the SLC19A3 gene on chromosome 2q36.6, encoding human thiamine transporter 2 (hTHTR2). Episodes of BTRBGD are often triggered by febrile illness. CASE REPORT: The patient was 2 years 10 months old male child presented with fever and progressive acute encephalopathy associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus infection. MRI revealed bilateral symmetrical high signal involving both basal ganglia and medial thalami which is swollen with central necrosis, initially diagnosed as acute necrotizing encephalomyelitis with increased severity. Genetic analysis revealed BTRBGD. CONCLUSION: BTRBGD requires high index of suspicion in any patient presenting with acute encephalopathy, characteristic MRI findings (that are difficult to differentiate from necrotizing encephalopathy), regardless of the existence of a proven viral infection.

Immune modulator therapy compared with vitrectomy for management of complicated intermediate uveitis: a prospective, randomized clinical study.

PURPOSE: To compare the benefits and side effects of pars plana vitrectomy with those of systemic immune modulator therapy for patients with complicated intermediate uveitis. METHODS: This prospective clinical trial enrolled patients with recurrent intermediate uveitis who exhibited minimal improvement of visual acuity, despite injections of periocular steroids. Twenty patients were randomized to the pars plana vitrectomy group or oral steroid and cyclosporine-A group (10 eyes of 10 patients per group). Follow-up was performed for 24 months to study changes in visual acuity, binocular indirect ophthalmoscopy score, fluorescein angiography, and optical coherence tomography findings. RESULTS: Visual acuity (logarithm of the minimal angle of resolution) significantly improved from 0.71 to 0.42 (p=0.001) in the surgical group, whereas it improved from 0.68 to 0.43 (p=0.001) in the immune modulator therapy group. Seven patients (70%) in the surgical group gained ≥2 lines, and six patients (60%) in the immune modulator therapy group gained ≥2 lines (p=0.970). Fluorescein angiography and optical coherence tomography studies showed that six of seven pars plana vitrectomy patients who had cystoid macular edema experienced improvement, whereas two patients with diffuse macular edema did not experience improvement. In the immune modulator therapy group, three of six patients with cystoid macular edema did not experience improvement, whereas two patients with diffuse macular edema experienced improvement. CONCLUSIONS: Pars plana vitrectomy and immune modulator therapy resulted in significant improvement in visual function in patients with persistent inflammation secondary to chronic intermediate uveitis. Despite this success, there remains a need for the determination of optimal indications for the use of each modality. Immune modulator therapy was successful for the treatment of diffuse macular edema associated with chronic intermediate uveitis, whereas pars plana vitrectomy was not.

Immune modulator therapy compared with vitrectomy for management of complicated intermediate uveitis: a prospective, randomized clinical study / Terapia com imunomodulador ou vitrectomia para manejo de uveíte intermediária complicada: estudo clínico prospectivo e randomizado

ABSTRACT Purpose: To compare the benefits and side effects of pars plana vitrectomy with those of systemic immune modulator therapy for patients with complicated intermediate uveitis. Methods: This prospective clinical trial enrolled patients with recurrent intermediate uveitis who exhibited minimal improvement of visual acuity, despite injections of periocular steroids. Twenty patients were randomized to the pars plana vitrectomy group or oral steroid and cyclosporine-A group (10 eyes of 10 patients per group). Follow-up was performed for 24 months to study changes in visual acuity, binocular indirect ophthalmoscopy score, fluorescein angiography, and optical coherence tomography findings. Results: Visual acuity (logarithm of the minimal angle of resolution) significantly improved from 0.71 to 0.42 (p=0.001) in the surgical group, whereas it improved from 0.68 to 0.43 (p=0.001) in the immune modulator therapy group. Seven patients (70%) in the surgical group gained ≥2 lines, and six patients (60%) in the immune modulator therapy group gained ≥2 lines (p=0.970). Fluorescein angiography and optical coherence tomography studies showed that six of seven pars plana vitrectomy patients who had cystoid macular edema experienced improvement, whereas two patients with diffuse macular edema did not experience improvement. In the immune modulator therapy group, three of six patients with cystoid macular edema did not experience improvement, whereas two patients with diffuse macular edema experienced improvement. Conclusions: Pars plana vitrectomy and immune modulator therapy resulted in significant improvement in visual function in patients with persistent inflammation secondary to chronic intermediate uveitis. Despite this success, there remains a need for the determination of optimal indications for the use of each modality. Immune modulator therapy was successful for the treatment of diffuse macular edema associated with chronic intermediate uveitis, whereas pars plana vitrectomy was not.

RESUMO Objetivo: Comparar os benefícios e efeitos co laterais da vitrectomia via pars plana com os da terapia imunomo duladora sistêmica em pacientes com uveíte intermediária complicada. Métodos: Estudo clínico prospectivo incluiu pacientes com uveíte intermediária recorrente que apresentaram melhora minima da acuidade visual, apesar das injeções perioculares de esteroides. Vinte pacientes foram randomizados para o grupo de vitrectomia via pars plana ou esteróide oral e ciclosporina A (10 olhos de 10 pacientes por grupo). O acompanhamento foi de 24 meses para estudar al te rações na acuidade visual, o escore da oftalmoscopia binocular indireta, a angiofluoresceinografia e achados na to mográfica de coerência óptica. Resultados: A acuidade visual (logaritmo do ângulo mínimo de resolução) melhorou significativamente de 0,71 para 0,42 (p=0,001) no grupo cirúrgico, enquanto melhorou de 0,68 para 0,43 (p=0,001) no grupo da terapia imunomoduladora. Sete pacientes (70%) no grupo cirúrgico ganharam ≥2 linhas e seis pacientes (60%) no grupo da terapia imunomoduladora ganharam ≥2 linhas (p=0,970). Os estudos de angiofluoresceinografia e tomografia de coerência óptica mostraram que seis dos sete pacientes da vitrectomia via pars plana que apresentaram edema macular cistóide melhoraram, enquanto dois pacientes com edema macular difuso não apresentaram melhora. No grupo da terapia imunomoduladora, três dos seis pacientes com edema macular cistoide não apresentaram melhora, enquanto dois pacientes com edema macular difuso melhoraram. Conclusões: A vitrectomia via pars plana e a terapia imunomoduladora resultaram em melhora significative da função visual dos pacientes com inflamação persistente secundária a uveíte intermediária crônica. Apesar desse sucesso, continua sendo necessário determinar as melhores indicações para o uso de cada modalidade. A terapia imunomoduladora foi bem sucedida no tratamento do edema macular difuso associado à uveíte intermediária crônica, enquanto a vitrectomia via pars plana não foi.

Eyebrow Elevation as a Prognostic Factor for Success of Frontalis Suspension in Severe Congenital Ptosis.

PURPOSE: The study aims at evaluating eyebrow elevation as a prognostic factor for frontalis sling procedure success in patients suffering from severe congenital ptosis with poor levator function. PATIENTS AND METHODS: This is a retrospective study that included 66 eyelids of 57 patients selected from a surgical log database between January 2016 and June 2019. All of them underwent frontalis suspension surgery for treating severe congenital myogenic ptosis with poor levator function. Based on the absence or presence of brow elevation, patients were divided into two groups: 1 and 2, respectively. The latter was further subdivided into subgroup A with unilateral brow elevation and subgroup B with bilateral brow elevation. All included cases completed 6 months of follow-up after surgery. Postoperative functional outcomes in the form of margin reflex distance (MRD1) and palpebral aperture (PA) were recorded and correlated to preoperative brow elevation status. RESULTS: Both principal groups showed improvement of MRD1 and PA compared to the preoperative values. There was no statistically significant difference between both groups for the tested parameters in the 1st postoperative week. By the 6th postoperative month, MRD1 and PA showed statistically significant higher values in group 2 compared to group 1 (p<0.001). However, the difference between subgroups A and B was statistically insignificant for the same parameters. CONCLUSION: Eyebrow elevation is significantly associated with the success of frontalis suspension procedure. Hence, brow position evaluation should be included in the preoperative assessment of patients undergoing frontalis suspension for congenital ptosis.

Anterior Segment Optical Coherence Tomography (AS-OCT) Guided Reversal of Edematous Punctal Occlusion.

AIM: To evaluate the role of anterior segment-optical coherence tomography (AS-OCT) in the diagnosis of punctal stenosis and to compare punctal parameters before and after medical treatment. PATIENTS AND METHODS: The study was conducted on 40 eyes of 24 patients who had acquired inflammatory punctal stenosis and had persistent epiphora (persistent epiphora group - PEG), and 20 eyes of 10 subjects with normal punctal openings as a control group (control group - CG). We measured the outer punctal diameter (OPD), recorded the visibility of the internal punctum and punctal depth (PD) using AS-OCT, before and 1 month after treatment with preservative free methylprednisolone 5% eye drops. Punctal diameter, tear meniscus height (TMH) and Munk's score were compared to the control group before and after treatment. RESULTS: The mean OPD of the PEG before treatment (455.5 ± 174 µm) was significantly smaller than that of the CG (590.9 ± 106.6 µm) (P= 0.002). The mean OPD of the PEG significantly increased to 484.6 ± 175.5 µm after treatment (P <0.001). Also, the visibility of vertical canaliculus lumen and PD were restored in 70% of eyes. The TMH was much higher in the PEG than in the CG before treatment (P<0.05). However, after treatment the difference was not statistically significant. CONCLUSION: AS-OCT parameters were useful in monitoring and measuring the efficacy of medical treatment in relieving punctal edema, which subsequently resulted in reducing the epiphora symptoms.

The cosmetic outcome of external dacryocystorhinostomy scar and factors affecting it.

PURPOSE: To study the cosmetic outcome of external dacryocystorhinostomy (Ex-DCR) and to detect the factors affecting it. PATIENTS AND METHODS: Prospective randomized interventional study included forty patients who were treated by 40 Ex-DCRs. In twenty patients, medial canthal vertical incision was used and in the other twenty cases, subciliary incision was used. The skin was closed using vicryl 6-0 or prolene 6-0 interrupted sutures, and each one was randomly used in twenty patients (10 patients of each incision type). Cosmetic outcome was evaluated 6 months postoperative by the patients and by an oculoplastic surgeon on a four grades scale. Cosmetic results and its correlation to patients' age, sex, skin complexion, type of incision, and type of skin sutures were studied. RESULTS: The mean scar grading was 0.98 ± 1.0 and 1.3 ± 1.0 in patients' and examiner's assessment. About 27.5% described their scars as cosmetically significant. The cosmetic outcome was significantly affected by the type of incision with only 5% significant scars in subciliary incision group. Prolene 6-0 suture was associated with better cosmetic results with 15% significant scars. 50% of dark-skinned patients showed cosmetically significant scars. Although no correlation was found between patients' age and cosmetic outcome, pediatric patients showed higher tendency to scar visibility with mean scar grade 1.2 ± 1.0 and 1.5 ± 0.9 in patients' and examiner's assessment. CONCLUSION: Dark skinned and pediatric patients are more prone to visible Ex-DCR scar. The use of subciliary approach and prolene 6-0 skin sutures is associated with more favorable cosmetic outcome.

Orbital metastasis from hepatocellular carcinoma: report of 6 cases.

A series of 6 consecutive cases of orbital metastasis from hepatocellular carcinoma (HCC) were reported in the last 5 years. All patients were men. The age of patients ranged between 47 and 70 years. Four patients presented with recent onset of unilateral proptosis, 1 patient presented with inflammatory manifestations, and 1 patient presented with unilateral ptosis. Pain was present in 4 patients. Three patients had a previous history of HCC, while the orbital affection was the first manifestation of the disease in 3 cases. All patients had chronic hepatitis C. CT scan of 5 patients showed a mass in upper lateral orbital quadrant, and 1 patient had the mass in the upper central orbit. Bone changes (thinning, notching, or erosion) were detected in all patients. Diagnosis was confirmed by incision biopsy in all cases. Life span of 5 patients in the study had a mean of 10.2 (±2.3) months.

Molecular genetic study of Egyptian patients with macular corneal dystrophy.

AIM: To identify the underlying genetic defect in Egyptian patients with macular corneal dystrophy (MCD). METHODS: A clinical and molecular genetic study was performed on 11 patients from six families with MCD. Clinical diagnosis was confirmed by slit-lamp biomicroscopy and histopathological examination of corneal buttons following keratoplasty. The coding region of the carbohydrate sulfotransferase (CHST6) gene was amplified by polymerase chain reaction (PCR) in all affected subjects. This was followed by direct sequencing and restriction digest analyses. Enzyme-linked immunosorbent assay of antigenic keratan sulfate (KS) in patients' serum was also performed. RESULTS: Six homozygous mutations, of which three are novel, were identified within the coding region of CHST6 in six unrelated MCD families. The barely detectable level of antigenic KS in the serum of the affected individuals indicated that they all have MCD type I, including the subtype IA. CONCLUSIONS: This is the first report of a molecular genetic analysis of MCD in the Egyptian population. These data indicate the extensive allelic heterogeneity within CHST6 and further support its essential role in maintaining corneal transparency.

Novel CHST6 nonsense and missense mutations responsible for macular corneal dystrophy.

PURPOSE: To identify the underlying mutations in two unrelated British families with macular corneal dystrophy (MCD) by screening the carbohydrate sulfotransferase (CHST6) gene. DESIGN: Case reports and results of DNA analysis. METHODS: Two subjects from two British families with MCD were studied. The genetic status of CHST6 was determined for all members of these MCD families. In addition, sulfated keratan sulfate (KS) assay from the probands was also undertaken. CHST6 gene was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by sequencing and restriction digestion. Enzyme-linked immunosorbent assay (ELISA) was performed to assess KS presence in serum. RESULTS: Four compound heterozygous mutations were identified, three of which are novel. The ELISA showed that the probands were of MCD type I. CONCLUSIONS: These novel mutations are expected to result in loss of CHST6 function, which would account for the MCD phenotype.