Shwetha Mangalesh

Retinal Imaging of Infants on Spectral Domain Optical Coherence Tomography.

Spectral domain coherence tomography (SD OCT) has become an important tool in the management of pediatric retinal diseases. It is a noncontact imaging device that provides detailed assessment of the microanatomy and pathology of the infant retina with a short acquisition time allowing office examination without the requirement of anesthesia. Our understanding of the development and maturation of the infant fovea has been enhanced by SD OCT allowing an in vivo assessment that correlates with histopathology. This has helped us understand the critical correlation of foveal development with visual potential in the first year of life and beyond. In this review, we summarize the recent literature on the clinical applications of SD OCT in studying the pathoanatomy of the infant macula, its ability to detect subclinical features, and its correlation with disease and vision. Retinopathy of prematurity and macular edema have been discussed in detail. The review also summarizes the current status of SD OCT in other infant retinal conditions, imaging the optic nerve, the choroid, and the retinal nerve fibre in infants and children, and suggests future areas of research.

Enhanced volumetric visualization for real time 4D intraoperative ophthalmic swept-source OCT.

Current-generation software for rendering volumetric OCT data sets based on ray casting results in volume visualizations with indistinct tissue features and sub-optimal depth perception. Recent developments in hand-held and microscope-integrated intrasurgical OCT designed for real-time volumetric imaging motivate development of rendering algorithms which are both visually appealing and fast enough to support real time rendering, potentially from multiple viewpoints for stereoscopic visualization. We report on an enhanced, real time, integrated volumetric rendering pipeline which incorporates high performance volumetric median and Gaussian filtering, boundary and feature enhancement, depth encoding, and lighting into a ray casting volume rendering model. We demonstrate this improved model implemented on graphics processing unit (GPU) hardware for real-time volumetric rendering of OCT data during tissue phantom and live human surgical imaging. We show that this rendering produces enhanced 3D visualizations of pathology and intraoperative maneuvers compared to standard ray casting.

Differential systemic gene expression profile in patients with diabetic macular edema: Responders versus nonresponders to standard treatment

Introduction: Diabetic macular edema (DME) is a vision-threatening complication of diabetic retinopathy. The current practice of management is a trial and error method of using intravitreal antivascular endothelial growth factor (VEGF)” or steroids to treat the patient and watch the response. However, if the patients genetic profile helps us choose appropriate medicine, it would help customize treatment option for each patient. This forms the basis of our study. Materials and Methods: A case-control, prospective, observational series, where DME patients were treated with bevacizumab and subclassified as treatment naοve, treatment responders, and treatment nonresponders. Blood samples of 20 subjects were studied, with five patients in each of the groups (nondiabetic- group 1, treatment naοve- group 2, treatment responder- group 3, and treatment nonresponder-group 4). Whole blood RNA extraction followed by labeling, amplification and hybridization was done, and microarray data analyzed. Genes were classified based on functional category and pathways. Results: The total number of genes upregulated among all three experimental groups was 5, whereas 105 genes were downregulated. There were no common genes upregulated between the responders and nonresponders. There was only one gene upregulated between the diabetic and diabetic responders posttreatment. There were 19 genes upregulated and 8 genes downregulated in the inflammatory pathway in group 2 versus group 1. There were no downregulated genes detected in vascular angiogenesis and transcription group. There were identical numbers of genes up- and downregulated in the inflammatory pathway. Seventeen genes were upreguated and 11 genes downregulated in receptor activity, which remained the predominant group in the group classification. Discussion: In summary, this study would provide an insight into the probable signaling mechanisms for disease pathogenesis as well as progression. This type of study eventually would aid in developing or improvising existing treatment modules with a rational approach towards personalized medicine, in future addressing the differential responses to treatment.

Universal ocular screening of 1021 term infants using wide‐field digital imaging in a single public hospital in India – a pilot study

Universal eye screening of neonates is currently not standard of care. Early detection of abnormalities could offer prompt management and a reduction in visual morbidity. We report a pilot study using wide‐field digital imaging to screen all infants at birth to explore its feasibility as a tool for universal screening.

COMPARING THE OUTCOME OF SINGLE VERSUS MULTIPLE SESSION LASER PHOTOABLATION OF FLAT NEOVASCULARIZATION IN ZONE 1 AGGRESSIVE POSTERIOR RETINOPATHY OF PREMATURITY: A Prospective Randomized Study.

Purpose: To compare single versus 2-session laser photoablation for flat neovascularization in cases with Zone 1 aggressive posterior retinopathy of prematurity. Methods: Twenty-nine Asian Indian infants with aggressive posterior retinopathy of prematurity were randomized; each eye received 1 of 2 methods (29 each in Group A or B) proposed by the PHOTO-ROP group. Group A underwent single session laser to the avascular retina underlying the flat neovascularization by direct laser over the fronds. Group B underwent laser in 2 sessions; first, laser was delivered to the avascular periphery up to the flat neovascularization and 7 days later to the avascular bed exposed by the retraction of the fronds. Outcome and complications between the two groups were compared. Results: Mean birthweight and gestational ages were 1,276 g and 30.1 weeks, respectively. All eyes showed favorable outcome at a minimum 12-month follow-up. Hemorrhages after laser (41.4% vs. 17.2%, P < 0.001) were more common in the single laser group. Large hemorrhages (>1 disk diameter) seen in Group A took longer than 8 weeks to resolve and developed focal fibrosis. Conclusion: This study demonstrates that the two-staged laser procedure produces fewer and smaller hemorrhages and no fibrosis compared with a single session. Both methods have comparable favorable outcomes in Asian Indian infants.

Variations in the cone packing density with eccentricity in emmetropes

AimTo describe the parafoveal cone arrangement in emmetropic subjects and its variations with eccentricity, meridians and change in axial length in Indian eyes.MethodsWe imaged 25 subjects using compact adaptive optics (AO) retinal camera prototype, the rtx1. Imaging was done at 1, 2, and 3° eccentricity from the fovea in four meridians: nasal, temporal, superior, and inferior.ResultsA statistically significant drop in the cone packing density was observed from 2 to 3° (2° eccentricity=25 350/mm2 (5300/mm2, 8400–34 800/mm2) 3° eccentricity=20 750/mm2 (6000 mm2, 9000–33 670/mm2)) P<0.05. The spacing correspondingly increased with increase in distance from the fovea (2° eccentricity=6.9 μm (0.70 μm, 5.95–11.6 μm)) and 3°eccentricity=7.80 μm (1.00 μm, 6.5–13.5 μm) P<0.05. As the axial length increases, the cone density significantly decreases. Interocular variations were noted.ConclusionWith the advent of AO, visualization at the cellular level is now possible. Understanding the photoreceptor mosaic in the parafoveal space in terms of its density, spacing, and arrangement is crucial so as to detect early pathology and intervene appropriately. Newer therapeutic modalitites that are targeted at the cellular level like yellow micropulse laser, stem cells, gene therapy and so on may be better monitored in terms of safety and efficacy.

Macular edema in Asian Indian premature infants with retinopathy of prematurity: Impact on visual acuity and refractive status after 1-year.

Purpose: To report the impact of transient, self-resolving, untreated “macular edema” detected on spectral domain optical coherence tomography in Asian Indian premature infants with retinopathy of prematurity (ROP) on visual acuity (VA) and refraction at 1-year of corrected age. Materials and Methods: Visual acuity and refraction of 11 infants with bilateral macular edema (Group A) was compared with gestational age-matched 16 infants with ROP without edema (Group B) and 17 preterms infants without ROP and without edema (Group C) at 3, 6, 9 and 12 months of corrected age using Teller Acuity Cards and cycloplegic retinoscopy. Sub-group analysis of the previously described pattern A and B macular edema was performed. Results: Visual acuity was lower in infants with macular edema compared with the other two control groups throughout the study period, but statistically significant only at 3 months. Visual improvement in these infants was highest between the 3rd and 6th month and plateaued by the end of the 1st year with acuity comparable to the other two groups. The edema cohort was more hyperopic compared to the other two groups between 3 and 12 months of age. Pattern A edema had worse VA compared to pattern B, although not statistically significant. Conclusion: Macular edema, although transient, caused reduced VA as early as 3 months of corrected age in Asian Indian premature infants weighing <2000 g at birth. The higher hyperopia in these infants is possibly due to visual disturbances caused at a critical time of fovealization. We hypothesize a recovery and feedback mechanism based on the principles of active emmetropization to explain our findings.

Optical coherence tomography of the preterm eye: from retinopathy of prematurity to brain development

Preterm infants with retinopathy of prematurity are at increased risk of poor neurodevelopmental outcomes. Because the neurosensory retina is an extension of the central nervous system, anatomic abnormalities in the anterior visual pathway often relate to system and central nervous system health. We describe optical coherence tomography as a powerful imaging modality that has recently been adapted to the infant population and provides noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside. Optical coherence tomography has increased understanding of normal eye development and has identified several potential biomarkers of brain abnormalities and poorer neurodevelopment.

Assessment Of The Retinal Structure In Children With Incontinentia Pigmenti

Purpose: This report aims at expanding the current knowledge of retinal microanatomy in children with incontinentia pigmenti using hand-held spectral domain optical coherence tomography (SDOCT). Methods: We reviewed OCT scans from 7 children (4 weeks–13 years) obtained either in the clinic or during an examination under anesthesia. The scans were analyzed for anatomical changes in the outer and inner retina, by certified graders. Medical records were assessed for systemic findings. Results: We observed abnormal retinal findings unilaterally in three children. We found inner and outer retinal thinning temporally in two participants. This thinning was present prior to and persisted after treatment. One child showed a distorted foveal contour and significant retinal thickening secondary to dense epiretinal membrane and vitreomacular traction. All other children had normal retinae. Conclusion: Hand-held SDOCT imaging of the retina has brought to light additional retinal structural defects that were not previously reported or visualized via routine clinical ophthalmic examination including retinal photography. Despite a normal foveal structure and visual acuity, we identified inner and outer retinal thinning on SDOCT which may benefit from future functional assessment such as visual field testing.

Impact of improved neonatal care on the profile of retinopathy of prematurity in rural neonatal centers in India over a 4-year period

Purpose To report the reduction in the incidence and severity of retinopathy of prematurity (ROP) in rural India over a 4-year period following the introduction of improved neonatal care practices. Methods The Karnataka Internet Diagnosis of Retinopathy of Prematurity program (KIDROP), is a tele-medicine network that screens for ROP in different zones of Karnataka state in rural India. North Karnataka is the most underdeveloped and remote zone of this program and did not have any ROP screening programs before the intervention of the KIDROP in 2011. Six government and eleven private neonatal centers in this zone were screened weekly. Specific neonatal guidelines for ROP were developed and introduced in these centers. They included awareness about risk factors, oxygen regulation protocols, use of pulse oxymetry, monitoring postnatal weight gain, nutritional best practices, and management of sepsis. The incidence and severity of ROP were compared before the guidelines were introduced (Jan 2011 to Dec 2012) and after the guidelines were introduced (July 2013 to June 2015). Results During this 4-year period, 4,167 infants were screened over 11,390 imaging sessions. The number of enrolled infants increased from 1,825 to 2,342 between the two periods (P<0.001). The overall incidence of any stage ROP reduced significantly from 26.8% to 22.4% (P<0.001). The incidence of treatment-requiring ROP reduced from 20.7% to 16% (P=0.06), and of the treated disease, aggressive posterior ROP reduced from 20.8% to 13.1% (P=0.23) following introduction of the guidelines. Discussion Rural neonatal centers in middle-income countries have a large, unscreened burden of ROP. Improving neonatal care in these centers can positively impact the incidence and severity of ROP even in a relatively short period. A combined approach of a robust ROP screening program and improved neonatal care practices is required to address the challenge.