Evaluation of the Levels of Low-dose Topical Atropine (0.01%) in Aqueous and Vitreous Humor in Human Eyes.

SIGNIFICANCE: This is the first human study that confirmed penetration of 0.01% topical atropine in aqueous and vitreous humor in live human eyes. This supports the possible mode of action of atropine via posterior ocular structures. This knowledge will help improve the outcomes in myopia management. PURPOSE: The purpose of this study was to evaluate penetration of low-dose atropine 0.01% in aqueous and vitreous humor. METHODS: In this cross-sectional interventional pilot study, 48 cataract cases were divided into four groups (12 each), and 30 epiretinal membrane/macular hole cases were divided into three groups (10 each). One drop of 0.01% atropine was put in the eye to be operated. Aqueous humor samples were taken from patients undergoing cataract surgery at 60 ± 15 minutes in group 1, 120 ± 15 minutes in group 2, 240 ± 15 minutes in group 3, and 360 ± 15 minutes in group 4. Vitreous humor samples were taken from patients undergoing vitreoretinal surgery for epiretinal membrane/macular hole at 120 ± 15 minutes in group 1, 240 ± 15 minutes in group 2, and 360 ± 15 minutes in group 3. The assay of atropine was performed using liquid chromatography-mass spectrometry. RESULTS: Median concentrations of atropine in aqueous samples were 1.33 ng/mL (min-max, 0.6 to 6.46 ng/mL; interquartile range [IQR], 3.05 ng/mL) at 60 minutes, 2.60 ng/mL (min-max, 0.63 to 4.62 ng/mL; IQR, 1.97 ng/mL) at 120 minutes, 1.615 ng/mL (min-max, 0.1 to 3.74 ng/mL; IQR, 1.62 ng/mL) at 240 minutes, and 1.46 ng/mL (min-max, 0.47 to 2.80 ng/mL; IQR, 1.73 ng/mL) at 360 minutes, and those in vitreous samples were 0.102 ng/mL (min-max, 0 to 0.369 ng/mL; IQR, 0.366 ng/mL) at 120 minutes, 0.1715 ng/mL (min-max, 0 to 0.795 ng/mL; IQR, 0.271 ng/mL) at 240 minutes, and 0.2495 ng/mL (min-max, 0 to 0.569 ng/mL; IQR, 0.402 ng/mL) at 360 minutes, respectively. CONCLUSIONS: Measurable concentration of low-dose topical atropine (0.01%) was noted in aqueous and vitreous humor after instillation of a single drop of low-dose atropine. Muscarinic receptors located in the posterior segment such as the choroid and retina could be the possible site of action of low-dose atropine in myopia.

Effect of low-dose atropine (0.01%) on crystalline lens power among school-aged children with progressive myopia.

PURPOSE: To evaluate the change in crystalline lens power (LP) in a cohort of Indian children with progressive myopia receiving atropine (0.01%) compared with an untreated control group. DESIGN: Nonrandomised clinical trial. METHODS: The study included 120 children (70 in the atropine group; 50 in the control group) with progressive myopia (≥0.5 D/year) with a 1-year follow-up. The atropine group received 0.01% atropine eye drops once daily in both eyes, whereas the control group received no treatment. Changes in cycloplegic spherical equivalent, axial length (AL), keratometry (KER), anterior chamber depth (ACD) and lens thickness (LT) were recorded. LP was calculated using the formula proposed by Bennett. RESULTS: Mean myopia progression at year 1 was significantly less in the atropine group (-0.18 D [0.2]) than in the control group (-0.59 [0.21]; p < 0.001). The increase in AL was significantly different between the two groups (atropine: 0.21 mm [0.12]; control: 0.29 mm [0.11], p < 0.001). A significantly greater loss of LP was noted in the atropine group (-0.67 D [0.34]) than in the placebo group (-0.28 D [0.42]; p < 0.001). The change in LT was significantly different between the atropine and control groups (p = 0.02), whereas the change in ACD and KER was similar in the two groups. CONCLUSION: The greater loss of LP could contribute to the anti-myopia effect of atropine and should therefore be evaluated in studies reporting the efficacy of atropine on myopia to assess its actual effect on myopic progression.

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.

Horizontal gaze palsy with progressive scoliosis.

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare autosomal recessive condition characterized by absence of abduction and adduction movements with intact vertical eye movements and progressive scoliosis. Patients usually present by mid-childhood with complaints of progressive scoliosis. The clinical diagnosis of HGPPS can be further confirmed by the ROBO3 gene mutation on chromosome number 11. We present 2 Indian siblings who were incidentally diagnosed with HGPPS with synergistic convergence on regular eye examination; diagnosis was confirmed by radiological and genetic testing.

Impact of weight reduction on structural and functional parameters of the optic nerve in idiopathic intracranial hypertension.

PURPOSE: To evaluate the effect of weight reduction on the structural and functional parameters of the optic nerve in established cases of papilledema in Idiopathic Intracranial Hypertension (IIH). METHODS: A prospective observational study in early and established cases of papilledema in IIH presenting from December 2019 to February 2021. Functional parameters (visual acuity, contrast sensitivity, mean deviation, VER), structural parameters (RNFL, GCL-IPL, and optic disc height), and clinical grading of papilledema were measured at baseline and every 6 weeks for 6 months. All patients underwent medical (oral acetazolamide) and diet therapy. RESULTS: Mean body mass index (BMI) at presentation was 26.32 ± 3.52 kg/m² and the mean change in BMI over 6 months was 1.27 ± 0.50 kg/m². 67% of eyes had papilledema of grades 2-3 at the presentation. At the end of 6 months, 75% of eyes had grade 1 papilledema while 13% showed complete resolution. A reduction of 5.32 ± 3.58 in mean deviation (r = 0.316; p-value 0.01) and gain in VER P100 amplitude of 4.2 ± 2.7 µV (r = 0.40; p-value 0.003) were noted over 6 months with reduction in BMI over 6 months. A statistically significant reduction in optic disc height (ODH) was noticed with BMI reduction over 6 months (p = 0.0007; r = 0.45).A reduction of 1.72 ± 0.90 kg/m² (equivalent to 6.53% weight loss) in BMI was associated with a four-grade change in clinical grading of papilledema. CONCLUSION: Reduction in BMI had a significant impact on both structural and functional parameters of the optic nerve in IIH. The involvement of a well-certified dietician should be an integral part of treatment in IIH.

Cerebrospinal fluid proteins in idiopathic intracranial hypertension: An exploratory SWATH proteomics analysis.

PURPOSE: The pathogenesis of idiopathic intracranial hypertension (IIH) is currently poorly understood. This exploratory study aimed to identify potential cerebrospinal fluid (CSF) biomarkers in IIH cases compared to controls using SWATH-MS proteomics approach. EXPERIMENTAL DESIGN: CSF samples were collected prospectively from IIH cases and control subjects which were subjected to SWATH-MS based untargeted proteomics. Proteins with fold change > 1.5 or < 0.67 and p-value < 0.05 were considered significantly differentially expressed. Data are available via ProteomeXchange with identifier PXD027751. Statistical analysis was conducted in R version 3.6.2. RESULTS: We included CSF samples from 33 subjects, consisting of 13 IIH cases and 20 controls. A total of 262 proteins were identified in Proteinpilot search. Through SWATH analysis, we quantified 232 proteins. We observed 37 differentially expressed proteins between the two groups with 24 upregulated and 13 downregulated proteins. There were two differential proteins among overweight versus non-overweight IIH cases. Network for 23 proteins was highly connected in the interaction analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Neurosecretory, neuroendocrine, and inflammatory proteins were predominantly involved in causing IIH. This exploratory study served as a platform to identify 37 differentially expressed proteins in IIH and also showed significant differences between overweight and non-overweight IIH patients.

Low-dose atropine 0.01% for the treatment of childhood myopia: a pan-India multicentric retrospective study.

OBJECTIVE: The objective of this study was to assess the efficacy of low-dose atropine 0.01% in controlling myopia progression among Indian children over a 2-year period. METHODS: This retrospective study, conducted across 20 centres in India, monitored the progression of myopia over 2 years after initiating treatment with 0.01% atropine eye drops. This included children between 6 and 14 years with baseline myopia ranging from -0.5 D to -6 D, astigmatism≤-1.5 D, anisometropia ≤ -1 D and documented myopia progression of ≥0.5 D in the year prior to starting atropine. Subjects with any other ocular pathologies were excluded. RESULTS: A total of 732 children were included in the data analysis. The mean age of the subjects was 9.3±2.7 years. The mean myopia progression at baseline (1 year before starting atropine) was -0.75±0.31 D. The rate of myopia progression was higher in younger subjects and those with higher baseline myopic error. After initiating atropine, myopia progression significantly decreased to -0.27±0.14 D at the end of the first year and -0.24±0.15 D at the end of the second year (p<0.001). Younger children (p<0.001) and higher baseline myopia (p<0.001) was associated with greater myopia progression and poor treatment response (p<0.001 for both). CONCLUSION: Low-dose atropine (0.01%) effectively reduces myopia progression over 2 years in Indian children.

Current perspective: Cerebral visual impairment-The impending doom.

Cerebral visual impairment (CVI) has emerged as an important cause of morbidity in young children. CVI children often have a large number of visual symptoms along with motor abnormalities. It is the need of the hour to build an integrated approach towards their management. This article aimed to provide a comprehensive view of the manifestations, evaluation, and management of children with CVI.

Evaluation of retinal function and morphology in isoametropic amblyopia.

Purpose: To observe the photoreceptor anomalies in cases of ametropic amblyopia. Methods: A prospective study with 25 isoametropic amblyopic children in the age group of 5-14 years and 25 age-matched controls was done. Examination included refraction, best-corrected visual acuity (BCVA), and color vision. Adaptive optics (AO) and multifocal electroretinogram (mf-ERG) were done to assess the anatomy and function of photoreceptors. The subgroup analysis of the improved and non-improved groups was done. Results: The mean cone density in cases and control in the superior, temporal, and nasal quadrants was respectively as follows (21640 ± 5713, 24040 ± 3386, P = 0.01) (19755 ± 6282, 21832 ± 2911, P = 0.03) (19897 ± 5418, 22171 ± 3660, P = 0.01) (20768 ± 4799, 22819 ± 3241, P = 0.01). The amplitude of N1 wave and P1 wave in cases was significantly low compared to the controls. Cases with subnormal color vision had reduced BCVA (0.55 ± 0.018) in comparison to the children with normal response (0.350 ± 0.014). Cone density was also significantly reduced in children with subnormal color vision. Sixteen out of 25 cases showed BCVA improvement with spectacles. Baseline cone density was found to be significantly higher in the improved group. There was no correlation between BCVA and AO parameters. Conclusion: Patients with ametropic amblyopia show subnormal photoreceptor properties than controls. Low cone density may be associated with defective color vision and poor prognosis in these cases.

Comparison of Dichoptic Therapy Versus Occlusion Therapy in Children With Anisometropic Amblyopia: A Prospective Randomized Study.

PURPOSE: To compare a smartphone-based dichoptic video game with occlusion therapy in children with anisometropic amblyopia. METHODS: In this prospective, randomized, interventional study, 55 children aged 5 to 15 years with anisometropic amblyopia were randomized into two groups: the video game group (n = 27) played a dichoptic video game with adjusted contrast for 2 hours/day and the patching group (n = 28) received occlusion therapy of the non-amblyopic eye for 6 hours/day. All patients were evaluated for best corrected visual acuity (BCVA), near vision, contrast sensitivity, and near and distance stereoacuity at baseline and 1, 2, and 3 months. RESULTS: Mean distance BCVA improved from 0.74 ± 0.19 and 0.70 ± 0.18 logarithm of the minimum angle of resolution (logMAR) in the video game and patching groups, respectively, at baseline to 0.53 ± 0.19 and 0.49 ± 0.19 logMAR, respectively, at 3 months (P < .001 for both). Mean near vision was 0.82 ± 0.19 and 0.81 ± 0.17 logMAR in the video game and patching groups, respectively, at baseline and improved to 0.60 ± 0.16 and 0.63 ± 0.17 logMAR at 3 months (P < .001 for both). There was no significant difference in distance and near vision between the two groups at baseline and final follow-up visit. Contrast sensitivity was 1.41 ± 0.20 and 1.38 ± 0.20 in the video game and patching groups, respectively, at baseline and 1.74 ± 0.18 and 1.61 ± 0.21 at 3 months (P < .001 for both). At the final follow-up visit, contrast sensitivity was significantly better in the video game group compared to the patching group (P = .01). Near stereoacuity significantly improved only in the video game group (P = .006), whereas distance stereoacuity did not improve in either group. CONCLUSIONS: Dichoptic video game therapy showed better results in terms of improvement in contrast sensitivity and near stereoacuity and similar outcomes for distance and near vision when compared to patching in children with anisometropic amblyopia. However, the availability of interesting games is essential to maintain children's interest. [J Pediatr Ophthalmol Strabismus. 2023;60(3):210-217.].

Evaluation of optical coherence tomography angiography changes in nonarteritic anterior ischemic optic neuropathy.

Purpose: To study the long-term microvasculature changes at the macula and the optic disk in eyes with nonarteritic anterior ischemic optic neuropathy (NAION). Methods: Patients with acute NAION of less than 6 weeks duration were included. Optical coherence tomography angiography (OCTA) of the macula and the optic disk was performed at baseline, 3 and 6 months and compared with the controls. Results: The mean age of 15 patients was 52.25 (±9.06) years. The whole image superficial peripapillary density (42.49 ± 5.28) was significantly low when compared to that of control eyes (46.36 ± 2.09); similarly, radial peripapillary capillary density (49.35 ± 5.64) was also significantly reduced when compared to controls (53.45 ± 1.96, P < 0.05). These parameters showed significant progressive decrease at 3 and 6 months (P < 0.05). At the macula, both superficial (41.83 ± 3.64) and deep macular vasculature densities (47.30 ± 2.04) were significantly reduced when compared to control eyes (52.15 ± 4.84 and 55.13 ± 1.81, respectively). The vascular density at the macula remained stable at 3- and 6-months period. Conclusion: The study shows that the microvasculature in case of NAION is significantly reduced both in peripapillary area and in macular area.

Evaluation of change in objective cyclotorsion after various inferior oblique-weakening procedures.

PURPOSE: To study the effect of four types of inferior oblique-weakening procedures on ocular torsion: inferior oblique recession (IOR), recession and antero-positioning (RAP), anterior transposition as practiced by Elliot and Nankin (EN), and anterior and nasal transposition (ANT). METHODS: The medical records of 72 consecutive patients >10 years of age undergoing inferior oblique weakening for primary or secondary inferior oblique overaction (IOOA) with or without horizontal rectus surgery were reviewed retrospectively. The 106 included eyes were assigned to one of the four groups according to the type of inferior oblique-weakening procedure. The severity of IOOA and the amount of V pattern guided the choice of procedure. IOOA, disk-fovea angle (DFA), and the amount of V pattern were recorded preoperatively. Measurements were repeated postoperatively at 1 week, 4 weeks, and 3 months. Change in the DFA was used to study the change in objective cyclotorsion in all four groups. RESULTS: A significant incyclotorsional shift was seen in all four groups at postoperative 3 months. The mean reduction in excyclotorsion 3 months postoperatively was 3.65° ± 4.84° for IOR, 5.31° ± 4.64° for RAP, 6.10° ± 3.89° for EN, and 16.62° ± 8.72° ANT; it was significantly higher in the ANT group compared with the other three groups. Reduction in DFA was also correlated with preoperative DFA overall, and for all procedures except IOR (P ≤ 0.005). CONCLUSIONS: All four inferior oblique-weakening procedures reduced excyclotorsion; the largest reductions in our study were seen in cases treated using ANT of the inferior oblique.

Prevention and management of childhood progressive myopia: National consensus guidelines.

Myopia is a major public health problem worldwide, including India, with the global prevalence of myopia increasing rapidly over decades. The clinical and socioeconomic impact of myopia is also expected to rise with rising prevalence. Therefore, the focus has now been shifted to prevent the incidence and progression of myopia. However, there is lack of any standardized guidelines for myopia management. This document aims to generate a national-level expert consensus statement on the management of childhood myopia in the Indian scenario. The expert panel of pediatric ophthalmologists consisted of 63 members who met in a hybrid meeting. A list of topics deliberating discussion in the meeting was provided to the experts in advance and they were instructed to provide their opinions on the matter during the meet. The panel of experts then gave their views on each of the items presented, deliberated on different aspects of childhood myopia, and reached a consensus regarding the practice patterns in the Indian scenario. In case of opposing views or lack of a clear consensus, we undertook further discussion and evaluated literature to help arrive at a consensus. A written document is prepared based on recommendations explaining definition of myopia, refraction techniques, components and methods of workup, initiation of anti-myopia treatment, type and timing of interventions, follow-up schedule, and indications for revised or combination treatment. This article formulates evidence-based guidelines for progressing myopes and pre-myopes and also establishes uniformity in the management of childhood myopia in the country.

A rare case of cortical blindness following vaccination against SARS-CoV-2.

A 61-year-old male presented with sudden loss of vision in both the eyes about 8 days after the first shot of coronavirus disease 2019 (COVID-19) vaccine (Covishield). On examination, the visual acuity was no perception of light in both the eyes. Contrast-enhanced magnetic resonance imaging (MRI) with diffusion-weighted imaging showed acute cerebral infarcts involving bilateral parieto-occipital region. Considering the temporal correlation with the vaccine shot and absence of any other precipitating factor, we hypothesized that this was probably an immunologic response to the vaccine.

A case of neuro retinitis in association with COVID-19.

A 36-year-old female presented with blurring of vision in one eye for 10 days after 1 month of an episode of COVID-19 infection. Her fundus showed disc edema with blurring of margins along with exudation around the fovea. Her C-reactive protein levels were raised. She responded well to oral steroids. A likely association with COVID-19 infection and its associated immune response was suspected.