Potential underlying mechanisms of ethambutol induced optic neuropathy: Evidence from in vitro to clinical studies.

Ethambutol is an antibiotic widely used for treatment of Mycobacterium species. Although it is safe to use in patients, the ocular toxic impact, including optic neuropathy and retinopathy, can be observed in patients using ethambutol. After discontinuation of the drug, the ocular toxic effects can be reversible in some patients, but some are not. Ethambutol-induced optic neuropathy has been recognized for more than six decades and the prevalence of optic neuropathy from a standard dose of ethambutol has been reported as 0.7-1.29%. Several factors associated with ethambutol-induced optic neuropathy include dosage/duration of drug, the medical conditions of patients such as renal and hepatic dysfunction and preexisting mitochondrial mutations. Currently, there is no specific treatment and prevention of ethambutol-induced optic neuropathy. In addition, the potential underlying mechanisms of ethambutol-induced optic neuropathy is still unclear. Therefore, this review aimed to summarize and discuss evidence from clinical, in vitro, and in vivo studies in order to explore the potential pathophysiology of ethambutol-induced optic neuropathy. Any contradictory findings are also included and discussed. The insights gained from the review will facilitate the discovery of novel approaches for prevention and treatment of optic neuropathy-induced by ethambutol.

Intraocular foreign body: Characteristics, visual outcomes, and predictive values of ocular trauma score.

Introduction: Retained intraocular foreign body (IOFB) remains an important cause of acquired visual impairment. The visual prognosis following treatments for eyes with retained IOFB was observed to be distinct from other mechanisms of open globe injury due to the specific nature and associated circumstances. This study evaluated the risk behaviors, visual results, and predictive values of Ocular Trauma Score (OTS) in determining visual outcomes in patients with IOFB that were not related to terrorism. Methods: Medical records of patients who underwent surgical interventions between January 2015 and December 2020 were retrospectively reviewed. Results: A total of one hundred and sixty-one patients (162 eyes) were recruited. The patients had a mean (standard deviation) age of 47.6 (14.0) years with working male predominance (93.2%). The majority of patients were injured by activities related to grass trimming (63.4%) and metallic objects were the main materials causing injuries (75.7%). Following treatments, the proportion of eyes having vision worse than 20/400 decreased from 126 eyes (77.8%) to 55 eyes (33.9%) at final visit. Ocular trauma score (OTS) had a high potential prediction for final vision in eyes in OTS categories 4 and 5. However, the discordance of final visual acuity distribution was observed in some subgroups of eyes in OTS categories 1 to 3. Conclusion: This study highlights the significance of IOFB related eye injuries in a tertiary care setting. Decision making on treatments should be carefully considered, particularly in eyes in lower OTS categories, in light of a rise in the proportion of patients who experience improved vision after IOFB removal.

Health-related quality of life of daily-life-affected benign essential blepharospasm: Multi-center observational study.

PURPOSE: To compare Thais' health-related quality of life (HRQOL) and severity grading, efficacy and safety in daily-life-affected benign essential blepharospasm (BEB) patients at baseline and after Botulinum toxin type A (BTX-A) treatment. DESIGN: Prospective-observational study. PARTICIPANTS: BEB patients with Jankovic rating scale (JRS) at least 3 in both severity and frequency graded from 14 institutes nationwide were included from August 2020 to June 2021. METHODS: Demographic data, HRQOL evaluated by the Thai version of EQ-5D-5L and NEI-VFQ-25 questionnaires, and severity grading score evaluated by Jankovic rating scale (JRS) at baseline, 1, and 3 months after the treatment were collected. The impact of the BTX-A injections and their complications were recorded. RESULTS: 184 daily-life-affected BEB patients were enrolled; 159 patients (86.4%) had complete data with a mean age of 61.40±10.09 years. About 88.05% were female, and 10.1% were newly diagnosed. Most of the patients had bilateral involvement (96.9%) and 12.6% had history of BEB-related accident. After BTX-A treatment, HRQOL improved significantly in 4 dimensions of EQ-5D-5L, except self-care. The EQ_VAS (mean±SD) was 64.54±19.27, 75.13±15.37, 73.8±15.85 (p<0.001) and EQ-5D-5L utility score was 0.748±0.23, 0.824±0.19 and 0.807±0.19 at baseline, 1, 3 months after treatment, respectively. From NEI-VFQ-25, HRQOL also improved in all dimensions, except eye pain. The JRS improved in all patients. Self-reported minor adverse events were 22.6%, which mostly resolved within the first month. CONCLUSION: Daily-life-affected BEB impacted HRQOL in most dimensions from both generic and visual-specific questionnaires. BTX-A treatment not only decreased disease severity, but also improved quality of life.

Reference Database of Inner Retinal Layer Thickness and Thickness Asymmetry in Healthy Thai Adults as Measured by the Spectralis Spectral-Domain Optical Coherence Tomography.

INTRODUCTION: The study aimed to determine a reference database of the thickness and intraocular thickness asymmetry of total retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) in healthy Thai subjects measured by the Spectralis spectral-domain optical coherence tomography. METHODS: This cross-sectional study recruited the healthy subjects age ≥18 years, having spherical refraction within ±6 diopters and cylindrical refraction ±3 diopters, from a hospital's personnel and the people visiting the ophthalmology department. Only 1 eye of each subject was randomly selected for an analysis. Macular images were obtained using posterior pole thickness scan protocol over a 24° × 24° area at the center of the fovea. The automated retinal thickness segmentation values of total retina and three inner retinal layers were calculated for the mean and the mean intraocular thickness difference between superior and inferior retinal hemispheres. The influence of age, gender, and axial length on thickness and thickness asymmetry of individualized retinal layer was evaluated. RESULTS: 252 subjects were included in study with a mean (SD) age of 46.7 (15.8) years, and 120 (47.6%) were males. According to the Early Treatment Diabetic Retinopathy Study map, the inner ring area was the thickest location of the total retina (range; 326.0-341.5 µm), GCL (range; 47.7-52.7 µm), and IPL (range; 39.9-42.1 µm), whereas the thickest location of RNFL was at the outer ring area (range; 18.8-47.5 µm). For posterior pole intraocular thickness asymmetry, the greatest mean ± SD difference was observed for total retina (9.0 ± 2.2 µm), followed by RNFL (9.9 ± 3.2 µm) and GCL (2.7 ± 0.6 µm), and the lowest mean difference was noted for IPL (2.4 ± 0.5 µm). The thickness and thickness asymmetry of each retinal layer were variably influenced by age, gender, and axial length; however, these factors had a minimal influence on the thickness asymmetry maps of GCL and RNFL. CONCLUSION: The reference database of the macular thickness and thickness asymmetry from this study would be beneficial in determining physiologic variations of the OCT parameters in the healthy Thai population.

Phacoemulsification Versus Phacotrabeculectomy in Primary Angle-closure Glaucoma With Cataract: Long-Term Clinical Outcomes.

PRECIS: Phacotrabeculectomy was more effective in reducing intraocular pressure (IOP) and glaucoma drugs than phacoemulsification alone in primary angle-closure glaucoma (PACG) eyes with cataract but was associated with more postoperative complications, up to 5 years after surgery. PURPOSE: The purpose of this study was to compare long-term clinical outcomes of phacoemulsification versus phacotrabeculectomy in PACG eyes with cataract. PATIENTS AND METHODS: The 2 initial prospective randomized controlled trials recruited PACG eyes with cataract using the same criteria and randomized these eyes to receiving either phacoemulsification or phacotrabeculectomy. Clinical data up to 5 years of follow-up were pooled for retrospective analysis. RESULTS: Clinical data of 35 patients in the phacoemulsification group and 44 patients in the phacotrabeculectomy group were analyzed. At 5 years after surgery, the mean IOP was decreased by 20.7% and 29.5% from before surgery to 5 years after phacoemulsification and phacotrabeculectomy, respectively (P<0.001 for both groups). Phacotrabeculectomy was significantly more effective than phacoemulsification in reducing IOP up to 5 years after surgery (P<0.001). At 5 years, the mean number of glaucoma drugs required±1 SD was 1.6±1.2 in the phacoemulsification group, and 0.7±1.0 in the phacotrabeculectomy group (P=0.004). Phacotrabeculectomy was associated with more postoperative complications than phacoemulsification up to 5 years (25 complications in the phacotrabeculectomy group versus 6 in the phacoemulsification group, P<0.001). CONCLUSIONS: Phacoemulsification alone reduces IOP and the need for glaucoma drugs in PACG eyes with cataracts for up to 5 years. Phacotrabeculectomy was more effective in reducing IOP and glaucoma drugs than phacoemulsification alone but was associated with more postoperative complications, up to 5 years after surgery.

Clinical Characteristics, Treatment Outcomes and Predictive Factors in Optic Neuritis.

BACKGROUND: The causes, clinical presentations and treatment outcomes of optic neuritis are distinct among different populations. Early diagnosis based on clinical presentations plays an important role in treating optic neuritis patients. OBJECTIVE: The study aimed to determine clinical characteristics, treatment outcomes and predictive factors of treatment outcomes in optic neuritis patients with and without demyelinating disease. METHODS: A retrospective descriptive study of optic neuritis patients carried out between January 2009 and December 2016 was done. Univariate analysis and multivariate logistic regression analysis were used to evaluate the predictive factors of treatment outcomes. RESULTS: Among 150 patients with optic neuritis, 58 patients were diagnosed with Neuromyelitis Optica Spectrum Disease (NMOSD), 23 patients were diagnosed with Multiple Sclerosis (MS) and 69 patients were idiopathic. The age at presentation in the NMOSD group was significantly younger than the MS group and the idiopathic group. The female:male ratio was significantly lower in the idiopathic group than in the NMOSD group. The initial Best Corrected Visual Activity (BCVA) of 20/20-20/60 (p = 0.001) and the idiopathic group (p =0.030) was associated with good visual outcomes. Initial BCVA of < 20/200 (p = 0.009) and the NMOSD group (p < 0.001) was associated with poor visual outcomes. CONCLUSION: NMOSD is a more common cause of optic neuritis than MS in Thai population. Female patients with poor initial VA, poor response to steroids treatment, and presenting recurrent attacks are highly suspicious for NMOSD. Optic neuritis without associated demyelinating disease has a better visual outcome and lower recurrence rate.

Comparison of self-measured diurnal intraocular pressure profiles using rebound tonometry between primary angle closure glaucoma and primary open angle glaucoma patients.

PURPOSE: To document the diurnal intraocular pressure (IOP) profile with rebound tonometry performed by primary glaucoma patients in non-clinic environment. PATIENTS AND METHODS: Fifty-three medically-treated eyes of 31 primary angle closure glaucoma (PACG) and 22 primary open angle glaucoma (POAG) patients with no previous eye surgery were recruited. Diurnal IOP was measured 5 times per day at four-hourly intervals from 08:00 to 24:00 for 1 week in patients' study eye using rebound tonometry in a non-clinic environment. The diurnal IOP profiles were compared between PACG and POAG eyes. RESULTS: For both PACG and POAG eyes, mean patient-measured IOP was highest in the morning, gradually decreased over the course of a day, and was lowest by midnight (p < 0.001). The diurnal IOP fluctuation ± 1 standard deviation (SD), as documented by SD in daily IOP values, was lower in PACG group (1.6 ± 1.1 mmHg) than in POAG group (2.0 ± 1.2 mmHg; p = 0.049). The mean trough IOP ± 1 SD was higher in PACG group (12.9 ± 2.8 mmHg), compared to POAG group (11.5 ± 3.8 mmHg; p = 0.041). The mean IOP level at midnight ± 1 SD in PACG group (14.0 ± 3.2 mmHg) was higher than that in POAG group (12.1 ± 3.7 mmHg; p = 0.013). CONCLUSIONS: IOP in primary glaucoma patients was highest in the morning, and decreased over the course of a day in non-clinic environment. Treated diurnal IOP fluctuation seemed to be greater in POAG than PACG eyes.

Optic Disc and Macular Imaging in Blind Eyes from Non-glaucomatous Optic Neuropathy: A Study with Spectral-domain Optical Coherence Tomography.

The purpose of this study was to determine and compare the optic disc and macular thickness measurements using two spectral-domain optical coherence tomography (SD-OCT) instruments in long-standing blind eyes diagnosed with non-glaucomatous optic neuropathies (NGON). A prospective observational case-series design was used. Twelve eyes from 12 NGON patients with no light perception for at least 6 months underwent optic disc and macular imaging with Cirrus HD-OCT and Spectralis OCT. The correlation between the peripapillary retinal nerve fibre layer (PRNFL) and macular ganglion cell layer and inner plexiform layer (GCL+IPL) thicknesses, and between the duration of no light perception (NLP) and PRNFL/GCL+IPL thicknesses were determined using Spearman's correlation analysis. The mean average PRNFL thickness was 55.9 ± 4.8 µm for Cirrus HD-OCT, which was significantly thicker than that measured by Spectralis OCT (31.9 ± 7.4 µm; p < 0.001). The mean central macular thickness on Cirrus HD-OCT was normal, but there was global thinning at the other macular areas. The mean average GCL+IPL thickness on Cirrus HD-OCT was 51.8 ± 5.8 µm. There was a good correlation between average PRNFL thickness and GCL+IPL thickness (r = 0.830, p = 0.002); however, there was no significant correlation between the duration of NLP to the average PRNFL thickness (on either instruments) or GCL+IPL thickness on Cirrus HD-OCT (p > 0.7). These results show that there was residual PRNFL thickness in NGON eyes with NLP, which varied significantly between SD-OCT instruments. The values of the residual PRNFL and GCL+IPL thicknesses in blind eyes (the "floor" effect) may be useful for prognostic purposes for patients with partial optic atrophy.

Agreement of patient-measured intraocular pressure using rebound tonometry with Goldmann applanation tonometry (GAT) in glaucoma patients.

This study aims to determine the agreement of patient-measured intraocular pressure (IOP) using rebound tonometry with ophthalmologist-measured IOP using Goldmann applanation tonometry (GAT). Fifty-three glaucoma patients used rebound tonometry (Icare ONE, Icare Finland Oy., Finland) to measure their own IOP in ambient environments for 1 week, 5 times per day. Clinic IOP measurements were performed by ophthalmologists using GAT and by patients using rebound tonometry on examination days 1, 4 and 7 of the same week. The agreement between the two tonometries was evaluated by modified Bland-Altman plots and intra-class correlation coefficient (ICC) was determined. Differences in ICCs of them among the three examination days were evaluated by bootstrap resampling analysis. Respective within-measurement ICC of GAT and rebound tonometry were 0.98 and 0.94 on Day 1, 0.98 and 0.93 on Day 4, and 0.96 and 0.92 on Day 7. In a modified Bland-Altman plot, the mean difference ±1 standard deviation (SD) between the two tonometries was 0.15 ± 0.65 mmHg (p = 0.682). Between-measurement ICC were 0.66, 0.76 and 0.73 on the 3 examination days. There was no significant difference among ICCs. In conclusion, patient-measured IOP using rebound tonometry and ophthalmologist-measured IOP using GAT demonstrate good agreement.

Treatment Outcomes and Predictive Factors in Pediatric Ocular Myasthenia Gravis.

OBJECTIVE: To determine demographic data, clinical presentations, investigations, treatment regimens, and clinical outcomes in pediatric ocular myasthenia gravis patients, and to find predictive factors for clinical outcomes such as resolution of disease, development of generalized symptoms, or final amblyopia. MATERIAL AND METHOD: This retrospective descriptive study of the medical records of 14 patients (male 6,female 8) less than 15 years that had ocular myasthenia gravis at Chiang Mai University Hospital between January 2006 and December 2012 was done. Univariate analysis was used to evaluate the predictive factors for clinical outcomes. RESULTS: Mean age of onset was 6.96±4.65 years (range 0.58-14 years). All patients presented with ptosis (100%) and 67% with strabismus. The mean oftotalfollow-up time is 6.30±3.84 years (range 1.25-14.25 years). None ofthe patients developed generalize myasthenia gravis. Only one patient had amblyopia at final presentation. Presenting age, gender strabismus at initial presentation, and positive neostigmine or edrophonium test did not affect resolution of disease nor final amblyopia. CONCLUSION: The most common clinical presentation in pediatric OMG was ptosis. Most patients could control the disease only by medications. There were no predictive factors affecting resolution of disease nor final amblyopia.