Ethambutol toxicity: Expert panel consensus for the primary prevention, diagnosis and management of ethambutol-induced optic neuropathy.

Ethambutol use may lead to permanent vision loss by inducing a dose- and duration-dependent optic neuropathy. This has been of concern to ophthalmologists and physicians both; however, ethambutol continues to be used because of its anti-mycobacterial action with relative systemic safety. Recently, the guidelines of the Revised National Tuberculosis Control Programme of India have been revised to allow for fixed dose and longer duration of ethambutol use; this is likely to result in an increase in vision-threatening adverse effects. Taking cognizance of this, neuro-ophthalmologists, infectious disease specialists, and scientists met under the aegis of the Indian Neuro-Ophthalmology Society to deliberate on prevention, early diagnosis, and management of ethambutol-related toxic optic neuropathy. The recommendations made by the expert group focus on early suspicion of ethambutol toxicity through screening at the physician's office and opportunistic screening by the ophthalmologist. Further, they focus on an early diagnosis through identification of specific clinical biomarkers and on management in way of early stoppage of the drug and supportive therapy. This statement also describes the mechanism of reporting a case of toxic optic neuropathy through the Pharmacovigilance Programme of India and emphasizes the need for spreading awareness regarding vision-threatening adverse effects among patients and healthcare workers.

Ethambutol Optic Neuropathy: Vigilance and Screening, the Keys to Prevent Blindness with the Revised Anti-tuberculous Therapy Regimen.

There has been change in the guidelines for the management of tuberculosis in India. The new guidelines advocate the daily use of Ethambutol for both intensive and continuation phase of the treatment. This may be a matter of concern as increased cumulative dose may lead to increase in incidence of toxic optic neuropathy due to ethambutol. Indian Neuro-Ophthalmology Society has taken cognizance of the issue and has come-up with guidelines for prevention and early detection of the toxic optic neuropathy.

Spectacle Coverage among Urban Schoolchildren with Refractive Error Provided Subsidized Spectacles in North India.

SIGNIFICANCE: Provision of subsidized spectacles to schoolchildren with refractive error in Delhi was associated with increased spectacle coverage. PURPOSE: Studies involving free spectacle distribution and self-purchase of spectacles often report poor compliance. We assessed 1-year spectacle coverage among schoolchildren with refractive error who were provided subsidized spectacles. METHODS: This was a study of a prospective cohort of 10,114 students from 20 randomly selected schools of Delhi. Children were presumed to have refractive error when unaided visual acuity was worse than or equal to 6/12 in either eye and a best-corrected visual acuity better than or equal to 6/9.5 in both eyes (n = 1503). Children with unmet need of spectacles (presenting with a visual acuity worse than 6/9.5 in the worse eye) were provided subsidized spectacles (n = 1191). Coverage was established by direct observation at baseline and after 1 year through unannounced visits. RESULTS: Mean age of cohort was 12.0 ± 2.0 years, and 566 (37.7%) were girls. Baseline spectacle coverage was 29.3% (95% confidence interval [CI], 27.1 to 31.7%), which improved to 65.9% (95% CI, 56.0 to 61.6%) among all children (n = 1470) and 58.8% (95% CI, 56.0 to 61.6%) among children with unmet need (n = 1163) at 1 year. Uptake of the subsidized spectacles was 98.6%. On multivariate regression, the odds of spectacle use were greatest when unaided vision was poor: 55.5% when visual acuity was better than or equal to 6/9.5, 74.8% when visual acuity was 6/19 to 6/60 (adjusted odds ratio, 2.5; 95% CI, 1.7 to 3.5), and 91.5% when visual acuity was worse than 6/60 (adjusted odds ratio, 3.1; 95% CI, 1.0 to 9.5). Sex (boys, 66.3%; girls, 65.3%) and socioeconomic status (lower, 58.6%; middle, 61.8%; upper middle, 70.7%) were not associated with coverage. Increasing maternal education and baseline spectacle use were associated with coverage. However, 38.0% were wearing spectacles prescribed by the project, and 61.9% of the spectacles being used at 1 year were purchased in the open market. CONCLUSIONS: Spectacle coverage after 1 year increased through a subsidized spectacle scheme, particularly for children with poor uncorrected vision.

Steroids versus No Steroids in Nonarteritic Anterior Ischemic Optic Neuropathy: A Randomized Controlled Trial.

PURPOSE: To examine the role of oral steroid therapy in the treatment of nondiabetic cases of acute nonarteritic anterior ischemic optic neuropathy (NAAION). DESIGN: Randomized double-blind clinical trial. PARTICIPANTS: Thirty-eight patients with acute nondiabetic NAAION divided into 2 arms of 19 patients each. One arm constituted the cases and the other constituted the controls. METHODS: Cases received oral steroid therapy and were designated the steroid group, whereas controls received placebo and were designated the nonsteroid group. Best-corrected visual acuity (BCVA), visual evoked response (VER), and OCT were performed at baseline, 1 month, 3 months, and 6 months after recruitment into the trial. MAIN OUTCOME MEASURES: Best-corrected visual acuity, VER, and retinal nerve fiber layer changes on OCT. RESULTS: Both groups showed significant improvement in BCVA, VER latency, and resolution of disc edema on OCT parameters over 6 months. Final outcome showed no statistically significant difference with regard to visual acuity, although VER was better in the steroid group (P = 0.011). Best-corrected visual acuity, VER amplitude, and VER latency (P = 0.02, P = 0.02, and P = 0.04, respectively) showed a greater percentage improvement in the steroid group, which also saw a faster resolution of disc edema on OCT (1-month follow-up). CONCLUSIONS: Oral steroids in acute NAAION did not improve the visual acuity significantly at 6 months. However, they improved resolution of disc edema significantly and enabled a greater improvement in VER parameters. This subtle benefit of oral steroids in NAAION is clinically unimportant and does not provide support for its use.

Retinal nerve fiber layer and ganglion cell layer changes on optical coherence tomography in early multiple sclerosis and optic neuritis cases.

PURPOSE: To study the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) changes on optical coherence tomography in early multiple sclerosis (MS) patients. METHODS: A prospective cohort study was conducted at a tertiary care center. Patients of early MS (expanded disability status scale <3) with or without optic neuritis (ON) and idiopathic ON were included. Twenty age-matched individuals were taken as controls. Changes in RNFL and GCL thickness were evaluated along with the correlation with visual function parameters such as visual acuity, contrast sensitivity, and visual evoked response at first visit and again at six months. RESULTS: Forty-four patients of MS with or without ON (24 and 20 patients respectively), 29 patients with idiopathic ON, and 20 healthy controls constituted the cohorts. Mean LogMAR best-corrected visual acuity was found to be significantly reduced in all groups except fellow eyes (FE) of ON group. Mean values of average RNFL thickness and values in superior, temporal, and inferior quadrant were significantly reduced. Similarly, overall mean values of average GCL-inner plexiform layer (IPL) thickness and values in superior, superonasal, superotemporal, inferonasal, and inferotemporal quadrant were significantly reduced in all groups except FE of ON group (P < 0.05). All the visual parameters significantly correlated with GCL + IPL thickness. CONCLUSION: GCL + IPL thickness is a more sensitive clinical structural marker than RNFL in early MS with/without ON and ON patients and correlates with all the visual parameters better than RNFL thickness.

Evaluation of the Protective Effect of NMDA/Non-NMDA Receptor Antagonists Against Ethambutol Induced Retinal Toxicity Using ERG in Wistar Rats.

To study the protective effect of NMDA and non-NMDA receptor antagonists against ethambutol (EMB) induced retinal toxicity in Wistar rats using flash electroretinogram (ERG). Rats were randomized into four groups: Group-1 received vehicle. Group-2 received oral EMB (200 mg/kg/day). Group-3 and 4 were fed with oral EMB along with memantine (MEM) (1 mg/kg, ip) and trimetazidine (TMZ) (3mg/kg, ip) respectively. All treatments were continued up to 28 days. ERG was recorded at 0 and 21st day using green and white lights. Ethambutol and 2, 2' ethylene diimino dibutyric acid (EDBA) levels were quantified in rat body fluids and tissues using LC-MS/MS. A higher rate of rat mortality was observed between 21st and 28th day, 21st day considered for ERG recording among groups. Ethambutol did not cause any significant change in 'a'-wave amplitude of rat ERG but caused a predictable decrease in 'b'-wave amplitude of the rat ERG on the 21st day. Memantine treatment showed a significant (P=0.029) protection against the fall of 'b'-wave amplitude on 21st day. Interestingly, we found that plasma levels of EMB in memantine treated rats were significantly reduced when compared to the positive control group. Memantine reversed the effects of EMB on 'b'-wave of rat ERG suggests its protective role. We suggest MEM may be considered as a possible preventive treatment modality for EMB induced vision toxicity warranting further clinical investigations.

Fabrication and Validation of Gyro-Dot-Optomotor Response Device using Gold Fish to Study Drugs Affecting Visual Perception.

An appropriate model to predict the effect of xenobiotics on the vision perception in neuropsychoharmacological studies is of great importance in drug development and toxicity studies. The present study valuated the effect of CNS stimulant, depressant and therapeutic agents known to have ocular toxicity on ptomotor response (OMR) using goldfish in a newly developed device. A digital light processing aided gyrating poly-chromatic dotted pattern-OMR (Gyro-dot-OMR) analyzer was developed and standardized for this study in our laboratory. Goldfishes were exposed to varying concentrations of caffeine and pentobarbitone sodium to evaluate the effect of CNS stimulation and depression on OMR in white light. Ethambutol induced ocular toxicity was evaluated by intravitreal injection into both eyes of goldfishes. They were subjected for polychromatic Gyro-dot-OMR in both clock and anticlockwise directions. At the low concentration (5, 10 and 20 ng/mL) caffeine exposed animals showed significant (p<0.05) stimulant effect and the EC(50) of caffeine in goldfish was found to be 4.806 ng/mL. In contrast, pentbbarbitone sodium treated fishes showed significant (p<0.05) depressant effect with increasing the concentration. Ethambutol toxicity was reflected by the color iscrimination in the Gyro-dot-OMR pattern. For the first time, this model proved the possibility of running Irwin profile test on goldfish using Gyro-dot-OMR. This model successfully predicted ethambutol induced toxicity with poor discrimination of red-green color. This model can be used for predicting toxicity of drugs affecting vision perception.

Correlation Between Structural and Functional Retinal Changes in Parkinson Disease.

BACKGROUND: To evaluate structural changes in the retina and correlate those with visual function measurements in patients with Parkinson disease (PD). METHODS: A cross-sectional comparative study of 20 patients with PD and 20 age-matched healthy controls was conducted. Visual acuity, color vision, contrast sensitivity, visual fields, pattern visual-evoked response (VER), and multifocal electroretinogram were recorded to determine functional change, whereas structural changes were evaluated with retinal nerve fiber layer (RNFL) thickness, macular thickness, macular volume, and ganglion cell-inner plexiform layer complex (GCL-IPL) thickness using spectral domain ocular coherence tomography (SD-OCT). RESULTS: PD patients ranged from Stage 1-3, with median Stage 2 (Hoehn and Yahr Classification) with mean Unified Parkinson Disease Rating Scale III score of 19 ± 10.42, and average disease duration of 5.8 ± 2.78 years. Visual acuity, color vision, and visual fields were unaffected but contrast sensitivity was significantly worse than controls (P < 0.001). Multifocal electroretinogram values in the central 2° field revealed decreased foveal electrical activity, with increased pattern VER amplitude and latency. Significant RNFL thinning was observed in the average RNFL (P = 0.033), superior (P = 0.018), and temporal (P = 0.036) quadrants. Significant ganglion cell layer loss was captured on SD-OCT with average, minimum GCL-IPL, and all 6 sectors showing thinning (P ≤ 0.003). The functional changes correlated significantly with structural changes, disease duration, and severity. There was no correlation between structural changes in the retina and disease duration or severity. CONCLUSIONS: Subclinical visual dysfunction was observed in patients with PD with good structural-functional correlation. GCL-IPL thinning may be a more reliable parameter than RNFL thickness for structural alterations of the retina in patients with PD.

Controversies in neuro-ophthalmology: steroid therapy for traumatic optic neuropathy.

BACKGROUND: There is an increase in the incidence of traumatic optic neuropathy (TON) due to increasing urbanization and rapid spurt in the number of motor vehicles on the road. Despite early presentation and ease of diagnosis the visual outcomes in TON are still limited. There is also significant confusion about the timing, dose and efficacy of steroid treatment in its management. PURPOSE: To provide a clinical update of the pros and cons of steroid therapy for TON. DESIGN: The paper is a retrospective review of the currently available literature in the English language indexed in PubMed. METHODS: A PubMed search was conducted by the authors using the following terms: Traumatic optic neuropathy, megadose, steroids, methylprednisolone. Relevant original articles, review articles, and case reports related to the topic of discussion were evaluated and discussed in the paper. RESULTS: There is no prospective randomized control trial evaluating the effect of steroids in TON. There are varying reports on the effect of steroid therapy from significant improvement to no difference compared to observation. CONCLUSION: The decision to give steroids to patients with TON has to be on an individual case to case basis and must involve informed consent from the patient. There are documented advantages and disadvantages of steroid therapy and a prospective, randomized, controlled trial is necessary comparing steroids, surgery and observation before definitive management can be evolved.

An unusual cause of optic atrophy in a child.

A 13-year-old child presenting with gross visual impairment was diagnosed as a case of optic atrophy. However, radiological investigations revealed osteopetrosis, which, though rare, can result in optic atrophy. The aim of this case report is to highlight this possibility while evaluating cases of optic atrophy in young patients.

Clinical profile and short-term outcomes of optic neuritis patients in India.

PURPOSE: To evaluate the clinical profile and short-term visual outcome of optic neuritis (ON) patients in India. MATERIALS AND METHODS: In this prospective study carried out over a period of 3 years, 99 eyes of 83 ON patients were examined and followed up for 10.8 ± 8.2 months for type of presentation, recurrence rate, and visual outcome. RESULTS: Mean age was 27.6 ± 8.8 years. Female preponderance was seen (70% of cases). Papillitis (53.5% of eyes) was more common than retrobulbar neuritis (46.5% of eyes). Bilateral presentation was seen in 19.3% cases. Baseline median logMAR visual acuity (VA) was 1.6 ± 0.8, which improved to 0.2 ± 0.6, with approximately 64% of eyes retaining VA of 20/40 or more. Two patients had previous diagnosis of multiple sclerosis (MS). MS was newly diagnosed in two patients. Recurrence was seen in 16% of eyes and was more common in cases of retrobulbar neuritis. CONCLUSION: The clinical profile of ON in Indian patients is different from that in the Western population. Unlike reported in the Western literature, papillitis is frequent in the Indian setup, with lower recurrence rates but poorer outcomes.

Evaluation of periosteal fixation of lateral rectus and partial VRT for cases of exotropic Duane retraction syndrome.

PURPOSE: The purpose of this study is to evaluate the lateral rectus periosteal fixation and partial vertical rectus transpositioning (VRT) as treatment modalities to correct exotropic Duane retraction syndrome (Exo-DRS). MATERIALS AND METHODS: Prospective interventional case study of cases of Exo-DRS with limitation of adduction. A total of 13 patients were subdivided into two groups. Six patients underwent only lateral rectus periosteal fixation (group A) and seven patients also underwent partial VRT (group B). Assessment involved prism bar cover test, abduction and adduction range, extent of binocular single visual field and exophthalmometry. These tests were repeated at 1 week, 1 month and 3 months post-operatively and data analyzed. RESULTS: The pre-operative mean values and ranges were 26.2 Δ (22-35) exotropia for group A and -21.3 Δ (14-30) exotropia for group B. The post-operative mean and range was +0.6 Δ esotropia (+20 to -8) for group A and 8 Δ (-2 to -20) exotropia for group B. Mean grade of limitation of abduction changed from -3.8 to -3.6 versus -3.6 to -2.8 and mean grade of limitation of adduction changed from -1.9 to -0.7 versus -1.5 to -0.5 in the groups A and B respectively. Mean binocular single visual field changed from 14.7° to 23.3° in group A and 11.8° to 26.4° in the group B respectively. CONCLUSION: Lateral rectus periosteal fixation is an effective surgery to correct the exodeviation, anomalous head posture and improving adduction in Exo-DRS and partial VRT in addition is effective in improving abduction and binocular single visual fields.

Bilateral intraocular dirofilariasis.

Ocular dirofilariasis mostly presents as a subconjunctival or eyelid lesion. Intraocular dirofilarial infestation is rare. We report a case of a young woman who was accidentally detected to have a live motile worm in the anterior segment in one eye and a cystic lesion on the optic disc in the other eye. To our knowledge, bilateral intraocular dirofilariasis has never been reported.

Factors predicting recurrence in successfully treated cases of anisometropic amblyopia.

CONTEXT: Recurrence after successful treatment of amblyopia is known and understanding the risk factors could help effective management. AIM: To measure incidence of recurrence in successfully treated cases of anisometropic amblyopia and evaluate factors predicting it. SETTINGS AND DESIGN: Cohort Study at a tertiary level institution. MATERIALS AND METHODS: Successfully treated anisometropic amblyopes aged 4-12 years were followed up for 1 year after stopping therapy. Best corrected visual acuity (BCVA), refractive error, stereoacuity and contrast sensitivity were evaluated at baseline and follow-up. STATISTICAL ANALYSIS: Intergroup analysis with appropriate tests: Chi-square test, Fisher's exact test, Wilcoxon rank sum test and paired t-test. RESULTS: One hundred and two patients with mean age at diagnosis 7.06 µ 1.81 years were followed-up for a mean duration of 1.0 µ 0.2 years. The mean pre-treatment BCVA (LogMAR score) at diagnosis was 0.73 µ 0.36 units which improved to 0.20 µ 0.00 with treatment and after 1 year of stopping treatment was 0.22 µ 0.07. Thirteen (12.74%) patients showed amblyopia recurrence during follow-up. Risk of recurrence was higher with older age of onset of treatment (6.64 µ 1.77 years without recurrence v/s 8.53 µ 1.39 years with recurrence, P = 0.0014). Greater extent of improvement of VA (P = 0.048) and final VA at stopping occlusion (P = 0.03) were associated with higher recurrence. Binocularity status or stereoacuity changes were not associated with risk of recurrence. CONCLUSIONS: Significant numbers of children suffer recurrence of amblyopia after stopping therapy. Older age, better BCVA after stopping therapy and greater magnitude of improvement in BCVA are important risk factors for recurrence. Careful follow-up is essential for early detection and management of recurrence.

Evaluation of changes in retinal nerve fiber layer thickness and visual functions in cases of optic neuritis and multiple sclerosis.

CONTEXT: Retinal nerve fiber layer (RNFL) thinning has been demonstrated in cases of optic neuritis (ON) and multiple sclerosis (MS) in Caucasian eyes, but no definite RNFL loss pattern or association with visual functions is known in Indian eyes. AIM: To evaluate RNFL thickness in cases of ON and MS, and to correlate it with visual function changes in Indian patients. SETTINGS AND DESIGN: Cross-sectional case-control study at a tertiary level institution. MATERIALS AND METHODS: Cases consisted of patients of (i) typical ON without a recent episode (n = 30:39 ON eyes and 21 fellow eyes), (ii) MS without ON (n = 15;30 eyes) while the controls were age-matched (n = 15; 30 eyes). RNFL thickness was measured using the Stratus 3 °CT. The visual functions tested included the best-corrected visual acuity (BCVA), contrast sensitivity, stereopsis, visual evoked responses, and visual fields. STATISTICAL ANALYSIS USED: Intergroup analysis was done using ANOVA and Pearson's correlation coefficient used for associations. RESULTS: RNFL thickness was reduced significantly in the ON and MS patients compared to the controls (P-0.001). Maximum loss is in the temporal quadrant. Lower visual function scores are associated with reduced average overall RNFL thickness. In ON group, RNFL thinning is associated with severe visual field defects while contrast sensitivity has strongest correlation with RNFL in the MS group. CONCLUSIONS: RNFL thickness is reduced in ON and MS cases in a pattern similar to Caucasians and is associated with the magnitude of impairment of other visual parameters. Contrast sensitivity and stereoacuity are useful tests to identify subclinical optic nerve involvement in multiple sclerosis.

Evaluation of FD2 (Frisby Davis distance) stereotest in surgical management of intermittent exotropia.

AIM: To evaluate Frisby Davis distance (FD2) stereotest for determining the timing of surgical intervention in intermittent exotropia (X(T)). METHODS: A prospective case-control study was conducted including 30 patients with X(T) and 30 age-matched controls. Stereoacuity was measured preoperatively and 3 months postoperatively using FD2 for distance and TNO and Randot for near. RESULTS: Preoperative distance stereoacuity was 43.83 ± 35.51 arcsec (median 30 arcsec; range 10-120) which improved postoperatively to 27 ± 33.74 arcsec (median 15 arcsec; range 5-120) (p=0.001). Cases with FD2 stereoacuity worse than 70 arcsec did not show significant improvement. Mean preoperative near stereoacuity by TNO was 94.00 ± 79.48 arcsec (median 60 arcsec) and Randot was 50.33 ± 39.23 arcsec (median 30 arcsec) which improved to 80.00 ± 80.08 arcsec (median 60 arcsec) and 34.17 ± 57.00 arcsec (median 20 arcsec), respectively, after surgery (both p=0.001). The controls had a mean distance stereoacuity of 14.66 ± 4.13 arcsec (median 15 arcsec; range 5-20) and near stereoacuity of 63.00 ± 21.35 arcsec (median 60 arcsec (TNO)) and 23.66 ± 5.07 arcsec (median 20 arcsec (Randot)). There was a significant correlation between FD2 and Randot in the cases but not in controls (p=0.005), however no correlation was found between TNO and FD2. CONCLUSIONS: Distance stereoacuity is reduced in X(T) to a greater extent than the near stereoacuity and both improve after surgery. FD2 is useful for deciding timing of surgery and a stereoacuity worse than 20 arcsec is an indication for surgical intervention. A preoperative distance stereoacuity which is worse than 70 arcsec implies a poor prognosis for stereoacuity improvement after surgery.

Is myopia a public health problem in India?

Myopia, a form of refractive error is a leading cause of visual disability throughout the world. In India uncorrected refractive errors are the most common cause of visual impairment and second major cause of avoidable blindness. Due to this the public health and economic impact of myopia is enormous. Although school vision screening programme is very successful in many states, still a significant number of school going children remain unidentified and the unmet need for correcting refractive errors in children appears to be significant.