Retinopathy of prematurity (ROP) is a neurovascular complication in preterm babies, leading to severe visual impairment, but the underlying mechanisms are yet unclear. The present study aimed at unraveling the molecular mechanisms underlying the pathogenesis of ROP. A comprehensive screening of candidate genes in preterms with ROP (n = 189) and no-ROP (n = 167) was undertaken to identify variants conferring disease susceptibility. Allele and genotype frequencies, linkage disequilibrium and haplotypes were analyzed to identify the ROP-associated variants. Variants in CFH (p = 2.94 × 10−7), CFB (p = 1.71 × 10−5), FBLN5 (p = 9.2 × 10−4), CETP (p = 2.99 × 10−5), and CXCR4 (p = 1.32 × 10−8) genes exhibited significant associations with ROP. Further, a quantitative assessment of 27 candidate proteins and cytokines in the vitreous and tear samples of babies with severe ROP (n = 30) and congenital cataract (n = 30) was undertaken by multiplex bead arrays and further validated by western blotting and zymography. Significant elevation and activation of MMP9 (p = 0.038), CFH (p = 2.24 × 10−5), C3 (p = 0.05), C4 (p = 0.001), IL-1ra (p = 0.0019), vascular endothelial growth factor (VEGF) (p = 0.0027), and G-CSF (p = 0.0099) proteins were observed in the vitreous of ROP babies suggesting an increased inflammation under hypoxic condition. Along with inflammatory markers, activated macrophage/microglia were also detected in the vitreous of ROP babies that secreted complement component C3, VEGF, IL-1ra, and MMP-9 under hypoxic stress in a cell culture model. Increased expression of the inflammatory markers like the IL-1ra (p = 0.014), MMP2 (p = 0.0085), and MMP-9 (p = 0.03) in the tears of babies at different stages of ROP further demonstrated their potential role in disease progression. Based on these findings, we conclude that increased complement activation in the retina/vitreous in turn activated microglia leading to increased inflammation. A quantitative assessment of inflammatory markers in tears could help in early prediction of ROP progression and facilitate effective management of the disease, thereby preventing visual impairment.

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OCT findings are useful to predict the probability of a disease, to diagnose it early, to differentiate between healthy and unhealthy tissue, and to assess the effect of therapeutic interventions in many systemic diseases.

Purpose:The purpose of this study is to detect the optic nerve head (ONH) and peripapillary perfusion in eyes with acute nonarteritic anterior ischemic optic neuropathy (NAION) compared to the fellow normal eyes using optical coherence tomography angiography (OCTA) and to compare with nonischemic disc edema (papilledema).Methods:Retrospective analysis of patients with unilateral NAION who underwent OCTA was performed. All patients underwent comprehensive ocular examination including visual field testing. ONH was imaged using 6 mm × 6 mm scan by Topcon DRI Triton® OCT system. Vascularity loss was analyzed using ImageJ software in diseased eyes in comparison to normal fellow eyes and eyes with papilledema.Results:Twenty-one patients (15 males, 6 females) with unilateral NAION and 9 patients (18 eyes) with papilledema were included in the study. In eyes with NAION, two distinct patterns of loss of vasculature were noted – (a) diffuse loss of microvasculature cuff and vascular network around the optic disc in all the patients (100%) and (b) additional area of sectoral loss of vasculature extending from the disc in 12 of the 21 eyes (57.14%). All 18 eyes with papilledema showed loss of the microvasculature cuff; however, none showed the focal pattern of vascular defect. The mean area of the peripapillary vascular zone in eyes with NAION was significantly lesser than that in normals. Of the 12 eyes with NAION with focal loss of vasculature, 11 correlated with visual field defects (91.6%).Conclusion:Deficient peripapillary choroidal vasculature is present in NAION and has a different pattern than in nonischemic disc edema and can cause corresponding visual field deficits.

Increasing rates of preterm births coupled with better survival of these infants have resulted in higher prevalence of systemic and ocular complications associated with prematurity. In addition to retinopathy of prematurity, infants who are born preterm may suffer from severe visual impairment as a result of hypoxic ischemic encephalopathy, hypoglycemia, and other metabolic imbalances. The effect of these processes on the anterior visual pathway may result in optic atrophy, optic nerve hypoplasia or optic disc cupping and affection of the posterior visual pathway leads to cortical visual impairment (CVI). Other ocular associations include strabismus, nystagmus, and ocular motor abnormalities such as tonic down gaze and defective saccades and pursuits. Cortical and subcortical involvement also manifests as defects in functional vision and these have not yet been completely understood. Children with CVI may have visual field defects, photophobia, defective visual processing, and deficient color vision. Since most of these children also suffer from additional systemic disabilities, evaluation, and management remains a challenge. However, early diagnosis and initiation of rehabilitation therapy can prove to be of significant benefit in these children.