Arachidonic acid metabolism regulates the development of retinopathy of prematurity among preterm infants.

Extremely preterm infants are at risk of developing retinopathy of prematurity (ROP), characterized by neovascularization and neuroinflammation leading to blindness. Polyunsaturated fatty acid (PUFA) supplementation is recommended in preterm infants to lower the risk of ROP, however, with no significant improvement in visual acuity. Reasonably, this could be as a result of the non-consideration of PUFA metabolizing enzymes. We hypothesize that abnormal metabolism of the arachidonic acid (AA) pathway may contribute to severe stages of ROP. The present study investigated the AA-metabolizing enzymes in ROP pathogenesis by a targeted gene expression analysis of blood (severe ROP = 70, No/Mild = 56), placenta (preterm placenta = 6, full term placenta = 3), and human primary retinal cell cultures and further confirmed at the protein level by performing IHC in sections of ROP retina. The lipid metabolites were identified by LC-MS in the vitreous humor (VH; severe ROP = 15, control = 15). Prostaglandins D2 (p = 0.02), leukotrienes B5 (p = 0.0001), 11,12-epoxyeicosatrienoic acid (p = 0.01), and lipid-metabolizing enzymes of the AA pathway such as CYP1B1, CYP2C8, COX2, and ALOX15 were significantly upregulated while EPHX2 was significantly (0.04) downregulated in ROP cases. Genes involved in hypoxic stress, angiogenesis, and apoptosis showed increased expression in ROP. An increase in the metabolic intermediates generated from the AA metabolism pathway further confirmed the role of these enzymes in ROP, while metabolites for EPHX2 activity were low in abundance. Inflammatory lipid intermediates were higher compared to anti-inflammatory lipids in VH and showed an association with enzyme activity. Both the placenta of preterm infants who developed ROP and hypoxic retinal cultures showed a reduced expression of EPHX2. These findings suggested a strong involvement of EPHX2 in regulating retinal neovascularization and inflammation. The study results underscore the role of arachidonic acid metabolism in the development of ROP and as a potential target for preventing vision loss among preterm-born infants.

Intraoperative challenges and outcomes of pediatric cataract surgery following glaucoma filtering surgery.

PURPOSE: To analyze the intraoperative challenges of cataract surgery in children, following glaucoma filtering surgery. METHODS: This was a retrospective study to analyze intra-op challenges and outcomes of pediatric cataract surgery in post-glaucoma filtration surgery eyes, between January 2007 and December 2019. RESULTS: We included 20 eyes of 16 children. The most common glaucoma surgery performed was trabeculectomy and trabeculotomy (14 eyes). The median age at the time of cataract surgery was 74.5 months. The most common cataract surgery performed was lens aspiration with posterior chamber intraocular lens implantation (LA + PCIOL) (9/20). The most common intraoperative challenge faced was difficulty in capsulorrhexis (ten eyes), followed by extension of primary posterior capsulotomy (six eyes). At the final follow up eight eyes had improvement in visual acuity, five eyes had stable visual acuity and five eyes had a drop in visual acuity. In 12/20 eyes IOL was implanted, nine eyes in-the-bag and three eyes had in ciliary sulcus. None of the IOLs in the bag had decentration of IOL. The median postoperative IOP (p = 0.12) and median number of postoperative AGM (p = 0.13) at 2 years remained stable compared to the preoperative values. The IOP remained well controlled in 4 eyes without anti-glaucoma medications and in 14 eyes with anti-glaucoma medications and none needed additional surgery for IOP control. Two eyes developed retinal detachment postoperatively. CONCLUSION: Cataract surgery in pediatric eyes with prior glaucoma surgeries, have challenges with capsulorrhexis and IOL stability. The visual outcomes were reasonably good so was the IOP control.

Agreement Between Virtual Reality Perimetry and Static Automated Perimetry in Various Neuro-Ophthalmological Conditions: A Pilot Study.

Our objective was to compare the agreement between virtual reality perimetry (VRP) (order of magnitude, OM) and static automated perimetry (SAP) in various neuro-ophthalmological conditions. We carried out a retrospective analysis of visual field plots of patients with various neuro-ophthalmological conditions who underwent visual field testing using VRP and SAP and between 1 January and 31 May 2022. Two fellowship-trained neuro-ophthalmologists compared the visual field defects observed on both devices. Per cent agreement was used to compare the interpretation of the two examiners on both techniques. The study criteria were met by 160 eyes from 148 patients (mean age 44 years, range 17-74 years). The most common aetiologies were optic atrophy due to various causes, optic neuritis, ischaemic optic neuropathy, and compressive optic neuropathy. Overall, we found good agreement between VRP and SAP for bitemporal (93.8%), hemianopic (90.8%), altitudinal (79.4%), and generalised visual field defects (86.4%). The agreement was acceptable for central/centrocaecal scotomas and not acceptable for enlarged blind spots. Between the two examiners there was good agreement for bitemporal (92.3%), hemianopic (82%), altitudinal (83%), and generalised field defects (76.4%). The results of our study suggest that VRP gives overall good agreement with SAP in various neuro-ophthalmological conditions, especially those likely to produce hemianopic, altitudinal, and generalised visual field defects. This could be useful in various settings; however, future larger studies are needed to explore real-world utilisation.

Successful visually guided eye movements following sight restoration after congenital cataracts.

Sensitive periods have previously been identified for several human visual system functions. Yet, it is unknown to what degree the development of visually guided oculomotor control depends on early visual experience-for example, whether and to what degree humans whose sight was restored after a transient period of congenital visual deprivation are able to conduct visually guided eye movements. In the present study, we developed new calibration and analysis techniques for eye tracking data contaminated with pervasive nystagmus, which is typical for this population. We investigated visually guided eye movements in sight recovery individuals with long periods of visual pattern deprivation (3-36 years) following birth due to congenital, dense, total, bilateral cataracts. As controls we assessed (1) individuals with nystagmus due to causes other than cataracts, (2) individuals with developmental cataracts after cataract removal, and (3) individuals with normal vision. Congenital cataract reversal individuals were able to perform visually guided gaze shifts, even when their blindness had lasted for decades. The typical extensive nystagmus of this group distorted eye movement trajectories, but measures of latency and accuracy were as expected from their prevailing nystagmus-that is, not worse than in the nystagmus control group. To the best of our knowledge, the present quantitative study is the first to investigate the characteristics of oculomotor control in congenital cataract reversal individuals, and it indicates a remarkable effectiveness of visually guided eye movements despite long-lasting periods of visual deprivation.

Pediatric myopic strabismus fixus: clinical features and surgical outcomes of silicone band loop myopexy.

PURPOSE: To evaluate the clinical profile of myopic strabismus fixus (MSF) in children and surgical outcomes of silicone band loop myopexy. METHOD: We retrospectively reviewed records of children presenting with MSF who underwent silicone band loop myopexy between January 2008 and December 2020 at a tertiary eye care center. Data concerning demographics, refractive error, axial length, extra-ocular motility, and ocular alignment pre-operatively and post-operatively, intra- and post-operative complications, ocular and systemic associations, were evaluated. The long-term effects of band loop myopexy on ocular alignment stability, motility improvement, and myopia progression were analyzed. Surgical outcome was defined as post-operative orthotropia or heterotropia less than or equal to 20 PD. RESULTS: A total of0 eyes of 7 patients (median age: 5 years; 5 boys and 2 girls) who underwent band loop myopexy were included in the study. Among them, three children underwent bilateral and four children underwent unilateral band loop myopexy. Medial rectus recession was performed only in two patients as a part of initial procedure. The median follow-up duration was 7 years. Most of the children, i.e. six of them presented with esotropia-hypotropia and only one patient presented with exotropia-hypotropia complex. The median pre-operative measurements were esotropia of 62.5 PD, hypotropia of5 PD, and exotropia of4 PD. Postoperative average primary position deviation measured was close to 9-10 PD of esotropia. The overall motility improved to -1 from -3. CONCLUSION: The clinical profile of MSF in children is almost similar to adults. This condition is a rare entity among adults as well as children. Majority of children with MSF presented with esotropia-hypotropia complex. Silicone band loop myopexy with or without medial rectus recession proves to be a reliable surgical procedure as it provides stable outcomes in terms of ocular alignment and motility among children.

Bilateral optic disc collaterals secondary to high-flow dural arteriovenous fistula: a diagnostic dilemma.

A man in his 80s, with a history of diabetes, hypertension and coronary artery disease, presented with bilateral painless progressive vision loss 2 years prior. His examination showed subnormal best corrected visual acuity of 20/50 and 20/80 in the right eye and left eye (LE), respectively, grade II relative afferent pupillary defect in LE, normal anterior segment, intra-ocular pressure (IOP) and defective colour vision in both eyes (BE). Fundus examination revealed optic disc pallor, disc collaterals and grade 2 hypertensive retinopathy in BE. Automated perimetry showed advanced field loss in BE. MRI of the brain and orbits with contrast showed signs of raised intracranial pressure, and magnetic resonance angiogram of the brain showed multiple arterio-venous channels along with the right transverse and sigmoid sinuses. The patient was referred to a neuroradiologist for further evaluation, and cerebral angiogram confirmed multifocal high-flow dural arterio-venous fistulae at right jugular foramen, transverse and sigmoid sinuses. He underwent Onyx liquid embolization.

Subnormal visual acuity after compliant amblyopia therapy: residual/refractory amblyopia or co-existing pathology? - a retrospective analysis.

Purpose: To assess the prevalence of alternate etiology/co-existing pathology among patients with amblyopia, and to characterize factors contributing to over-diagnosis of amblyopia. Methods: We retrospectively reviewed records of children (from 1 January 2016 to 31 December 2019) who were initially diagnosed as "amblyopia" but later an alternate diagnosis for subnormal vision was established. Patients who had a best corrected visual acuity (BCVA) of ≤20/32 (0.2 logMAR) after compliant amblyopia therapy were divided into 2 groups: those with refractory amblyopia (BCVA improvement from baseline <1 logMAR line) and residual amblyopia (BCVA improvement from baseline >1 logMAR line). Data was collected for presence/absence of amblyogenic risk factors, history, ocular examination, and investigations leading to the final alternate diagnosis. We analyzed the factors that contributed to the initial over-diagnosis of amblyopia using the diagnostic error evaluation and research (DEER) taxonomy tool. Results: During the study period, 508 children with an initial diagnosis of amblyopia met the study criteria. Among these 508 children, 466 were diagnosed to have amblyopia alone, while 26 children (5.1%, median age: 7 years, 17 boys: 9 girls) were revised to have an alternate diagnosis/co-existing pathology. These 26 patients comprised of 2 groups: children referred to us as amblyopia but rediagnosed to have an alternate diagnosis; and a second subset, initially diagnosed by us to have amblyopia, but later found to have alternate diagnosis/co-existing pathology. Subclinical optic neuritis (50%, 13 children), and occult macular dystrophy (OMD) (38.4%, 10 children) were the most frequent alternative diagnoses. Children with ametropic amblyopia (8/26, 30.7%) were most frequently misdiagnosed. Risk factors that led to an initial diagnosis of amblyopia were: high refractive error and heterotropia in 7 patients each (26.9%), anisometropia in 12 (46.1%), and prior pediatric cataract surgery in 4(15.3%). No improvement in BCVA in 21/26 (80.7%) children led to suspicion of co-existing etiology. Other clues were optic disc pallor (11), subnormal color vision (7), history of parental consanguinity in 7, and preceding febrile illness/rhinitis in 1 child. The DEER taxonomy tool suggested that the most common reasons for diagnostic errors were over-emphasis on amblyopia. Conclusion: Our study suggests that 5% of children diagnosed with amblyopia might have co-existing/alternate etiology. Most common co-existing etiologies were subclinical optic neuropathy, and OMD. No improvement in BCVA, subtle history and examination findings prompted further workup. Not considering co-existing etiologies was the most common reason for an initial overdiagnosis of amblyopia.

Myopic shift, refractive, and visual outcomes after 5 years of infantile cataract surgery: Our experience and review of literature.

PURPOSE: After infantile cataract surgery, axial elongation, induces a myopic shift that cannot be fully compensated by corneal flattening and the rate is unpredictable owing to the non-linear growth of the eye. The current prospective study assesses the myopic shift and visual outcomes in children undergoing cataract surgery in infancy over a follow-up period of 5 years. MATERIALS AND METHODS: A prospective study conducted at a tertiary eye care center to evaluate the five-year myopic shift, refractive and visual outcomes in infants, who underwent surgery for congenital cataract in infancy. The visual acuity, myopic shift and biometric changes are compared between the aphakia and pseudophakia group. RESULTS: The mean best-corrected visual acuity (BCVA) recorded in logMAR at 5 years for aphakia group was 0.92±0.44 and for pseudophakia group was 0.66±0.42. (pvalue: 0.002102). The myopic shift was noted to be -5.9+/-5.16 in the aphakia group whereas it was -9.01+/- 3.11 in the pseudophakia group (P value= 0.002101) at 5 years after surgery for infantile cataract. CONCLUSION: IOL implantation in eyes of infants undergoing cataract surgery is feasible in eyes that strictly satisfy the pre-operative inclusion criteria and the visual outcomes in these eyes are better compared to aphakia group at 5 years follow up. Eyes with primary IOL implantation had a higher myopic shift compared to ones without primary IOL implantation. Eyes undergoing primary IOL implantation, need higher under correction compared to the current available formulae.

Paracentral acute middle maculopathy in a patient with Myelin Oligodendrocyte glycoprotein antibody associated optic neuritis.

Purpose: There is insufficient literature reporting the concurrent occurrence of retinal ischemic lesions with optic neuritis. In this case report, we present a distinctive instance of Optic Neuritis with a positive Myelin Oligodendrocyte glycoprotein (MOG) antibody, accompanied by retinal ischemia manifesting as paracentral acute middle maculopathy (PAMM) lesions. Observations: Our patient is a 25-year-old female who tested positive for MOG antibodies and exhibited retinal PAMM lesions without any apparent underlying ischemic cause. She received intravenous pulse steroid therapy, and her symptoms and signs completely resolved one month later. Conclusion: PAMM can serve as an initial manifestation of Myelin Oligodendrocyte glycoprotein Antibody Associated Disease (MOGAD). This case has the potential to contribute to the existing literature, facilitating a deeper exploration of the pathophysiology of retinal ischemia in MOG associated optic neuritis.

Sound suppresses earliest visual cortical processing after sight recovery in congenitally blind humans.

Neuroscientific research has consistently shown more extensive non-visual activity in the visual cortex of congenitally blind humans compared to sighted controls; a phenomenon known as crossmodal plasticity. Whether or not crossmodal activation of the visual cortex retracts if sight can be restored is still unknown. The present study, involving a rare group of sight-recovery individuals who were born pattern vision blind, employed visual event-related potentials to investigate persisting crossmodal modulation of the initial visual cortical processing stages. Here we report that the earliest, stimulus-driven retinotopic visual cortical activity (<100 ms) was suppressed in a spatially specific manner in sight-recovery individuals when concomitant sounds accompanied visual stimulation. In contrast, sounds did not modulate the earliest visual cortical response in two groups of typically sighted controls, nor in a third control group of sight-recovery individuals who had suffered a transient phase of later (rather than congenital) visual impairment. These results provide strong evidence for persisting crossmodal activity in the visual cortex after sight recovery following a period of congenital visual deprivation. Based on the time course of this modulation, we speculate on a role of exuberant crossmodal thalamic input which may arise during a sensitive phase of brain development.

Ectopia Lentis: Clinical profiles in a large cohort of children from a Tertiary Eye Care network in India.

PURPOSE: To study the clinical presentations, visual, and refractive profiles of children with congenital ectopia lentis in a large cohort of patients from a tertiary eye care network in India. MATERIALS AND METHODS: A retrospective review of electronic medical records from December 2012 to December 2020 was conducted. Two hundred and ninety-seven consecutive children ≤18 years of age at presentation were identified and analyzed for demographic details, patient distribution, lens subluxation, visual, and refractive profiles before and after the interventions. RESULTS: Five hundred and ninety-four eyes of 297 (male 56%; n = 166) patients were analyzed. The mean age at presentation was 8.74 ± 3.89. Best-corrected visual acuity (BCVA) at presentation ranged from 0.3 logMAR to 3.5 logMAR; (Snellen: 6/9 - close to face [CF]) (mean 0.89 ± 0.68). High myopia (n = 201; 33.83%) and mild astigmatism (n = 340; 57.23%) were more frequent. Temporal (n = 108; 18.18%) subluxation was most common followed by superior. Lensectomy with limited vitrectomy was performed in 243 eyes of 127 patients (40.90%). Median preoperative BCVA was 1.0 (range: 0.3-3.5 logMAR; 20/40 - CF). Median postoperative BCVA was 0.5 logMAR (6/18) in the pseudophakic group and 0.6 logMAR (6/24) in the aphakic group. Spherical equivalent in myopic children reduced from -12.06 ± 6.84D to -1.57D (-0.25D to - 5.5D) in the pseudophakic group and +9.3D (+5.5D to 15.5D) in the aphakic group. CONCLUSION: This study is a large cohort of children presenting with ectopia lentis. Following intervention, an improvement in the median BCVA and refractive correction was noted in the entire cohort.