Fetal oxidative stress, micronutrient deficiency and risk of retinopathy of prematurity: a nested case-control study.

We hypothesized that fetal oxidative stress and micronutrient deficiencies contribute to higher incidence of retinopathy of prematurity (ROP) in developing countries. In a nested case-control study, preterm infants (< 37 weeks, < 1700 g) were included at birth and followed until 40 weeks post-menstrual age (PMA). Maternal, cord, and neonatal serum/plasma samples at 40 weeks PMA were frozen. Samples of "cases" with ROP and gestational age (GA) and birth weight-matched "controls" with no ROP (in 1:4 ratio) were thawed and analyzed. PRIMARY OUTCOME: MDA concentration in cord plasma. SECONDARY OUTCOMES: MDA in maternal and 40-week PMA plasma; copper, zinc, and vitamin A in maternal, cord, and 40-week PMA samples. Thirty-eight cases and 151 controls had a mean (SD) GA of 29.5 (1) and 29.9 (1) weeks respectively. Following were associated with ROP: higher MDA concentration in cord and 40-week PMA samples; lower copper and zinc in maternal serum; lower zinc and vitamin A in cord sample (all p < 0.05). MDA [adjusted OR (aOR) = 4.13 (95% CI 1.83-9.27)] and vitamin A [aOR = 0.09 (95% CI 0.02-0.4)] concentration in cord plasma and weight gain (g/kg/week) [aOR = 0.97 (0.95-0.99)] independently predicted ROP. CONCLUSION: Increased oxidative stress and deficiency of micronutrients from fetal life were associated with ROP. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/REF/2014/12/008174. What is Known: • In developing countries, there is a higher incidence of retinopathy of prematurity (ROP), but micronutrient deficiencies have not been adequately investigated as risk factors. • Few observational studies have shown an association between ROP and postnatal increase in malondialdehyde (MDA) levels and deficiencies of antioxidant vitamins and minerals, but none in cord blood. What is New: • High MDA, low zinc, and low vitamin A levels in cord blood and low copper and zinc levels in maternal blood are associated with the development of ROP. • On multivariable analysis, high cord blood MDA and low cord blood vitamin A are independent predictors of ROP.

Surgical outcomes of cataract surgery in anterior and combined persistent fetal vasculature using a novel surgical technique: a single center, prospective study.

PURPOSE: To study the complications and surgical outcomes of cataract surgery in patients of persistent fetal vasculature (PFV) with cataract. METHODS: In this prospective study, phacoaspiration with/without intraocular lens implantation (IOL) was done in 20 children (mean age 14.2 months) with unilateral cataract with anterior (n = 6) or combined (n = 14) PFV. The rentrolental vascularized membrane was cauterized and dissected circumferentially, followed by cauterization and resection of the PFV stalk. The outcome measures included fixation preference using the CSM (central, steady, maintained) method and intraoperative and postoperative complications in an 18-month follow-up. The difference in outcomes of anterior and combined PFV, as well as aphakic and pseudophakic eyes, was studied. RESULTS: CSM fixation was seen in 16 patients after 18 months. The intraocular lens was implanted in 16 eyes and 4 eyes with combined PFV were left aphakic. None of our patients had intraoperative bleeding. Visual axis obscuration was the major complication seen, requiring membranectomy in 8 children. Pupilloplasty was required with membranectomy in one eye. None of our patients developed glaucoma or retinal detachment. CONCLUSION: Timely surgical intervention and aggressive amblyopia therapy led to good visual results in our study. Poor prognosis was seen in combined PFV, aphakia, and microphthalmia.

Evaluation of Optic Nerve Sheath Diameter and Transcranial Doppler As Noninvasive Tools to Detect Raised Intracranial Pressure in Children.

OBJECTIVES: To compare the diagnostic accuracy of the ultrasonography-guided optic nerve sheath diameter with transcranial Doppler-guided middle cerebral artery flow indices against the gold standard invasive intraparenchymal intracranial pressure values in children. DESIGN: A single-center prospective cohort study. SETTING: PICU of a tertiary care teaching hospital in North India. PATIENTS: Eligible children (2-12 yr) are admitted to ICU and are undergoing intracranial pressure monitoring using an intraparenchymal catheter. Observations with a parallel measured intracranial pressure greater than or equal to 20 mm Hg were included as case-observations. Children with an invasive intracranial pressure of less than or equal to 15 mm Hg were taken as neurologic-control-observations and healthy children served as healthy-control-observations. INTERVENTIONS: The horizontal and vertical diameters of the optic nerves were measured, and averages were calculated and compared. Middle cerebral artery flow indices (pulsatility index and resistive index) were measured bilaterally and averages were calculated and compared in the three groups. Twenty-two measurements of optic nerve sheath diameter were assessed by two different observers in quick succession for interrater reliability. MEASUREMENTS AND MAIN RESULTS: A total of 148 observations were performed in 30 children. Four observations were excluded (intracranial pressure between 16 and 19 mm Hg). Of the 144 observations, 106 were case-observations and 38 were neurologic-control-observations. Additional 66 observations were healthy-control-observations. The mean optic nerve sheath diameter was 5.71 ± 0.57 mm in the case-observations group, 4.21 ± 0.66 mm in the neurologic-control-observations group, and 3.71 ± 0.27 mm in the healthy-control-observations group (p < 0.001 for case-observations vs neurologic-control-observations/healthy-control-observations). The mean pulsatility index in case-observations was 0.92 ± 0.41 compared with controls 0.79 ± 0.22 (p = 0.005) and the mean resistive index was 0.56 ± 0.13 in case-observations compared with 0.51 ± 0.09 (p = 0.007) in controls (neurologic-control-observations and healthy-control-observations). For the raised intracranial pressure defined by intracranial pressure greater than or equal to 20 mm Hg, the area under the curve for optic nerve sheath diameter was 0.976, while it was 0.571 for pulsatility index and 0.579 for resistive index. Furthermore, the optic nerve sheath diameter cutoff of 4.0 mm had 98% sensitivity and 75% specificity for raised intracranial pressure, while the pulsatility index value of 0.51 had 89% sensitivity and 10% specificity by middle cerebral artery flow studies. The sensitivity and specificity of 0.40 resistive index value in the raised intracranial pressure were 88% and 11%, respectively. Kendall correlation coefficient between intracranial pressure and optic nerve sheath diameter, pulsatility index, and resistive index was 0.461, 0.148, and 0.148, respectively. The Pearson correlation coefficient between two observers for optic nerve sheath diameter, pulsatility index, and resistive index was 0.98, 0.914, and 0.833, respectively. CONCLUSIONS: Unlike transcranial Doppler-guided middle cerebral artery flow indices, ultrasonography-guided optic nerve sheath diameter was observed to have a good diagnostic accuracy in identifying children with an intracranial pressure of greater than or equal to 20 mm Hg.

Efficacy of Ozurdex implant in recalcitrant diabetic macular edema--a single-center experience.

The purpose of this study is to report the efficacy of intravitreal Ozurdex implant in managing recalcitrant diabetic macular edema. Retrospective interventional non-randomized study of patients with recalcitrant diabetic macular edema who received intravitreal Ozurdex implant. Main outcome measures were change in the central macular thickness, visual acuity, and intraocular pressure. Sixty-seven eyes of 52 patients with recalcitrant diabetic macular edema with a mean duration of 45.4 ± 22.5 months (range 6-96 months) were studied. Mean central macular thickness decreased from 514.2 ± 177.8 µm at baseline to 394.3 ± 152.2 µm (p = 0.007), 301.8 ± 93.0 µm (p < 0.000), 316.4 ± 115.6 µm (p < 0.000), and 419.9 ± 186.3 µ (p = 0.03) at 1, 6, 12, and 24 weeks, respectively. Mean best corrected visual acuity changed from 0.82 ± 0.46 log MAR to 0. 69 ± 0.44 log MAR (p = 0.122), 0.61 ± 0.40 log MAR (p = 0.007), 0.65 ± 0.37 log MAR (p = 0.024), and 0.68 ± 0.49 log MAR (p = 0.091) at 1, 6, 12, and 24 weeks, respectively. Single injection of intravitreal Ozurdex implant led to progressive decrease in central macular thickness with maximum percentage decrease at 6 weeks (41.2 %) from the baseline which was maintained up to 12 weeks. Eight eyes showed transient rise in intraocular pressure at 2 months which was controlled by antiglaucoma medications.

Role of Anti-Vascular Endothelial Growth Factor (Anti-VEGF) in the Treatment of Retinopathy of Prematurity: A Narrative Review in the Context of Middle-Income Countries.

The rise in preterm births and higher survival rates of premature infants have led to a global increase in retinopathy of prematurity (ROP), a vasoproliferative retinal disorder common in premature infants. ROP is one of the leading causes of childhood blindness. Clinical manifestation of ROP ranges from mild abnormal retinal neovascularization to bilateral retinal detachment and vision loss. The incidence of ROP is higher in middle income countries, including India, which has the highest number of global preterm births. Low birth weight and low gestational age are the primary risk factors for ROP; however, anemia, cardiac defects, blood transfusion, apnea, sepsis, respiratory distress syndrome, high exposure to oxygen and poor postnatal weight gain may also contribute to its development. India has stringent ROP screening guidelines revised in 2018, and screening of infants with either birth weight <2000 grams or gestational age <34 weeks is mandated. With an improved understanding of the pathogenesis of ROP in the past decades and advances in clinical research, treatment for ROP has evolved from cryotherapy to laser retinal ablation. Most recently, anti-vascular endothelial growth factor (anti-VEGF) drugs have emerged as a favorable treatment option for zone-I and II ROP. This article reviews the current approaches for ROP treatment in India with a particular focus on anti-VEGF drugs. The article also integrates the understanding of safety and risk-benefit evaluation of the current approaches in ROP management. The review concluded that there is a need to increase the ROP screening not only for preterm and low birth weight but also for optimal gestational age infants with healthy birth weight. Anti-VEGF therapies have shown improved efficacy, although studies are required to establish the long-term safety.

Rapid regression of idiopathic multifocal choroiditis with intravitreal methotrexate-wide-field optical coherence tomography angiography-based study.

Wide-field optical coherence tomography angiography (OCTA) results in a patient of idiopathic multifocal choroiditis successfully treated with intravitreal methotrexate injections.

Longitudinal study of serpiginous choroiditis and serpiginous like choroiditis using wide field OCT angiography.

PURPOSE: To assess the ability of wide field Swept Source OCTA (SS-OCTA) imaging to detect morphological variations in Serpiginous Choroiditis (SC) and Serpiginous Like Choroiditis (SLC) in response to treatment and also analyze these findings quantitatively using Image J software. METHODS: Retrospective observational case series of nine eyes with clinical diagnosis of active SC and SLC, who underwent SS-OCTA and fundus autofluorescence (FAF) imaging at baseline and each follow up visit till 6 months. Morphological analysis was done by two independent graders and quantitative analysis to measure the size and intensity of lesion was done using publicly available Image J software at baseline and each follow up visit. DESIGN: Retrospective observational case series. RESULTS: Using SS-OCTA, all the active lesions followed a characteristic healing pattern. Active lesions appear well defined hypo flow void patches and as healing progressed, lesion became more ill-defined and iso-hyper- intense. Significant increase in mean intensity of the lesion could be apparent after 1 and 6 month of treatment. There was reduction in the size of lesions during follow up however this difference was not statistically significant. CONCLUSION: SS-OCTA could be a useful noninvasive tool to study the treatment response in SC/SLC both morphologically as well as quantitatively. Quantitative parameters need to be designed in further research studies to aid in uniform management and follow up of uveitis cases.

Impact of COVID-19-related lockdown on retinal disorders treated with intravitreal injections.

PURPOSE: To study functional changes in vision and morphological changes on optical coherence tomography (OCT) scans in patients where intravitreal therapy (IVT) with injections has been delayed due to COVID-19 pandemic lockdown. METHODS: Retrospective cross-sectional study included 77 eyes with the diagnosis of exudative age-related macular degeneration (eAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO), regularly receiving IVT with anti-vascular endothelial growth factor (Anti-VEGF) injections or dexamethasone implant and were not able to receive the injections as intended due to lockdown. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), and qualitative morphological features on OCT were analyzed pre- and post-therapy break off. RESULTS: The mean duration of IVT break-off was 57 days. Mean BCVA logarithm of minimum angle of resolution (logMAR) worsened from 0.33 (20/42) to 0.35 (40/44) (P = 0.02) and mean CFT increased from 297.90 µm to 402.16 µm (P < 0.01), from pretherapy break-off to return visit. Worsening of the visual acuity was seen across all the three disease cohorts, significantly more in the eyes with eAMD. CONCLUSION: Marginal decline in the visual acuity and worsening of the OCT features were observed as a result of delay in the IVT injections of DME, eAMD and RVO patients.

Preferred practice guidelines for retinopathy of prematurity screening during the COVID-19 pandemic.

Retinopathy of prematurity (ROP) is the leading cause of preventable infant blindness in the world and predominantly affects babies who are born low birth weight and premature. India has the largest number of surviving preterm births born annually. ROP blindness can be largely prevented if there is a robust screening program which detects treatment requiring disease in time. ROP treatment must be provided within 48 h of reaching this threshold of treatment making it a relative emergency. During the severe acute respiratory syndrome-coronavirus disease 2019 pandemic in 2020 ROP screening was disrupted throughout the world due to lockdowns and restriction of movement of these infants, their families, specialists and healthcare workers. The Indian ROP Society issued guidelines for ROP screening and treatment in March 2020, which was aimed at preserving the chain-of-care despite the potential limitations and hazards during the (ongoing) pandemic. This preferred practice guideline is summarized in this manuscript.

Efficacy of 0.01% low dose atropine and its correlation with various factors in myopia control in the Indian population.

We aimed to evaluate the efficacy and safety of low-dose atropine compared to placebo in the Indian population and also to study the impact of various modifiable and non-modifiable factors on myopia progression (MP) and drug efficacy (DE). It was a single-centre prospective placebo-controlled interventional study. 43 participants aged 6-16 years with progressive myopia received 0.01% atropine in the right eyes (treatment) and placebo in the left eyes (control) for 1-year. The main outcome measures were annual MP and axial length elongation (ALE) in treatment and control eyes and their percentage difference between two eyes (drug efficacy). Secondary outcome measures were the occurrence of any adverse events and the correlation of MP, ALE, and DE with various factors. 40 participants (80 eyes) completed the follow-up. After 1-year, MP was 0.25 D (IQR 0.13-0.44) and 0.69 D (IQR 0.50-1.0) (p < 0.001) in treatment and control respectively (63.89% reduction) with respective ALE of 0.14 mm (IQR 0.05-0.35) and 0.32 mm (IQR 0.19-0.46) (p < 0.001) (44.44% reduction). No adverse events were noted. Reduction in MP and ALE was statistically significant in all children irrespective of age-group, baseline MP, family history, screen-time, near and outdoor-time. The strongest determinants of annual MP were age (Treatment: r = - 0.418, p = 0.007; Control: r = - 0.452, p = 0.003) and baseline MP (Treatment: r = 0.64, p = 0.000; Control: r = 0.79, p = 0.000). Screen-time in control eyes was associated with greater ALE (r = 0.620, p = 0.042). DE was higher when outdoor time exceeded 2 h/day (p = 0.035) while the efficacy was lower with prolonged near activities (p = 0.03), baseline fast-progressors (p < 0.05) and history of parental myopia (p < 0.05). 0.01% atropine is effective and safe in retarding MP and ALE in Indian eyes.

Ophthalmic Complications in Pediatric Uveitis.

Purpose: We aim to look at the complications encountered by a cohort of pediatric uveitis patients from north India.Methods: Retrospectively, complications seen in patients younger than 16 years diagnosed with uveitis between January 2006 to March 2015 were noted.Results: Data of 104 children, with a mean follow-up of 3.40 ± 2.34 years was studied. Cataract (n = 42, 24.00%), band-shaped keratopathy (n = 32, 18.29%) and Glaucoma/OHT (n = 11, 6.29%) were most encountered complications at presentation. Glaucoma/OHT (29.71%; n = 52), cataract (18.86%; n = 33) and maculopathy (n=12;6.86%) were the most common complications at follow up. Maculopathy (35%) and Glaucoma/OHT (20%) were the most common causes of visual acuity ≤3/60.Conclusions: Cataract is the most critical complication in children with uveitis at presentation and raised intraocular pressure occurs at follow-up, perhaps attributed to the treatment. Maculopathy is the most common cause of blindness in these children.

'Stop-and-Slide' technique for trocar insertion during lens-sparing vitrectomy for retinopathy of prematurity.

The modern-day trocar cannula systems meant for adult eyes pose a challenge in infant's eyes with stage 4 retinopathy of prematurity (ROP) undergoing lens-sparing vitrectomy. This is primarily owing to the length of the trocar, globular lens, smaller axial length, and anteriorly displaced retina. We describe an inexpensive modification of the technique of trocar insertion in such cases wherein the trocar is inserted partially till the cannula impinges the sclera and thereon, the cannula slides over the trocar into the vitreous cavity. This obviates the need for complete insertion of the trocar into the vitreous cavity and hence limits the chances of inadvertent injury to the crystalline lens or the anteriorly lifted retina. We have experience in using this technique in 52 eyes of 44 infants over the past 2 years with no episode of iatrogenic lens touch or retinal break during trocar insertion.

Accidental Globe Perforation During Posterior Sub-Tenon's Injection of Triamcinolone Acetonide.

Complications of posterior sub-Tenon's steroid injections like glaucoma, cataract, sub-conjunctival hemorrhage and ptosis are well known. The authors present this photo essay to highlight a rare but serious complication of globe perforation secondary to posterior sub-Tenon's triamcinolone injection and describe its management. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:466-467.].

Change in the incidence and severity of Retinopathy of Prematurity (ROP) in a Neonatal Intensive Care Unit in Northern India after 20 years: Comparison of two similar prospective cohort studies.

PURPOSE: To report the change in incidence and severity of retinopathy of prematurity (ROP) in the neonatal unit of a tertiary hospital after a 20-year period. METHODS: A prospective cohort study of one-year duration was conducted between July 2013 and June 2014 in the neonatal intensive care unit (NICU) of a tertiary hospital. Inborn babies with birth weight ≤1700 g and gestational age ≤37 weeks were included. Change in incidence and severity of ROP were compared to a similar study in the same NICU between January and December 1993. RESULTS: The 2013 study included higher numbers of newborn infants than the 1993 study (293 vs. 157). The mean (SD) birth weight and gestational age of the infants in the 2013 study were significantly lower than the 1993 study [1288.6 (229.8) vs. 1378.1 (232.6) g); p = 0.0001 and 31.7 (2.1) vs. 32.2 (2.31) weeks; p = 0.04]. Nevertheless, the overall incidence of ROP decreased from 49% to 26.6% (p < 0.001) after the 20-year interval. The incidence of stage 3 ROP decreased non-significantly from 24.7% to 12.8% (p = 0.058). Multivariate logistic regression analysis showed that birth weight ≤1250 g and belonging to the 1993 cohort were independently associated with an increased risk of ROP after adjusting for covariates (p = 0.013). CONCLUSION: The incidence of ROP improved significantly over a 20-year period in association with improved NICU management strategies despite an increase in the number of eligible neonates with lower birth weights and gestational ages.

Posterior zone I retinopathy of prematurity: spectrum of disease and outcome after laser treatment.

OBJECTIVE: To report the morphological spectrum and outcome after laser treatment in posterior zone I retinopathy of prematurity. DESIGN: Retrospective, consecutive, interventional case series. METHODS: Review of charts and RetCam images of preterm infants with posterior zone I retinopathy of prematurity (defined as area within a circle, the radius of which extends from the center of the optic disc to the center of the macula) treated with confluent laser at a tertiary care referral institute between January 2006 and December 2015. Data was analyzed and tabulated using frequency and descriptive statistics to describe the demography, morphology, and outcome after laser treatment. RESULTS: Fifty-six eyes (28 infants) with a mean gestational age of 28.65 ± 2.18 weeks and birth weight of 1153.04 ± 251.51 g were analyzed. Forty-two (75%) eyes had persistent tunica vasculosa lentis and 25 (44.6%) had preretinal hemorrhages. All eyes had circumferential ROP and a poorly developed foveal vasculature. Four distinct morphological patterns were encountered: I - typical aggressive posterior retinopathy was seen in 36 (64.3%) eyes; II - atypical aggressive posterior retinopathy (14 eyes; 25%) had raised fibrovascular proliferation always on the nasal retina close to the optic disc; III - hybrid retinopathy of prematurity (4 eyes; 8.7%) had a mat-like fibrous proliferation on vascularized posterior retina; and IV - threshold retinopathy of prematurity seen in 2 (4.4%) eyes. An unfavourable outcome was seen in 44 (78.6%) eyes. CONCLUSIONS: Retinopathy of prematurity in posterior zone I presents with atypical morphology and poor outcomes despite confluent laser photocoagulation.

Optical coherence tomography angiography versus fluorescein angiography in diagnosing choroidal neovascularization in chronic central serous chorioretinopathy.

Purpose: Diagnosis of choroidal neovascular membrane (CNVM) is difficult in chronic central serous chorioretinopathy (CCSC) due to overlapping features of both on conventional dye angiography. Optical coherence tomography angiography (OCTA) allows a quick and noninvasive detection of CNVM in these eyes. We compared the fluorescein angiography (FA) features of CNVM with those of OCTA to assess the role of FA in detecting CNVM in CCSC eyes. Methods: Patients with CCSC undergoing FA, spectral domain (SD)-OCT, and OCTA were identified (March 2015-June 2015). Four retina specialists individually reviewed FA images (without OCTA and SD-OCT) to determine whether CNVM was present. In parallel, two other retina specialists reviewed all images (FA/SD-OCT/OCTA) for CCSC features and confirmed whether CNVM was present using OCTA as the gold standard. The inter- and intraobserver variability was measured by Kappa (k) coefficient. The FA features of CNVM were compared and correlated with those on OCTA. Results: Of 43 eyes (26 patients, mean age 45.6 ± 8.5 years, all males), a definite CNVM (detected by OCTA) was present in nine (20.9%) eyes. FA alone detected CNVM in 13 (30.2%) eyes [sensitivity 44.4% (95% confidence interval (CI): 11.9-76.9), specificity 73.5% (95% CI: 58.7-88.3), positive and negative predictive values 30.8% and 83.3%, respectively, and accuracy 67.44% (95% CI: 53.4-81.4)]. Conclusion: When compared with OCTA, the FA was unable to characterize CNVM in CCSC (with a very low sensitivity and moderate specificity) as none of the specific dye leakage patterns on FA correlated with CNVM seen on OCTA, limiting its usefulness and accuracy in detecting CNVM in these eyes.

Diagnosis and treatment of bilateral Coats disease in a 5-year-old girl.

A 5-year-old girl presented with decreased vision and outward deviation of her right eye. Fundus examination revealed multiple hard exudates in the macula in the right eye and nasal to the disk in the left eye. The patient was lost to follow-up in the near term but presented 9 months later with reduced vision and an increase in exudates in both eyes. RetCam fluorescein angiography confirmed the diagnosis of bilateral Coats disease.

An Update on Retinopathy of Prematurity (ROP).

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease affecting the retina of premature infants. The clinical spectrum of ROP varies from spontaneous regression to bilateral retinal detachment and total blindness. Between these two extremes lies the form of ROP, which is amenable to treatment with laser photocoagulation, anti-vascular endothelial growth factor drugs or surgery. Increasing rates of preterm births coupled with better survival rates but lack of uniform quality of neonatal care and delays in diagnosis have led to increasing ROP blindness. Atypical forms of Aggressive Posterior ROP are seen in heavier birth weight babies in developing countries. Prevention of ROP by following stringent protocols for supplemental oxygen, prevention of sepsis, timely screening and laser treatment by a concerted and collaborative effort of neonatologists and ophthalmologists are required to fight the blindness from ROP.