Correlation between tear levels of vascular endothelial growth factor and vitamin D at retinopathy of prematurity stages in preterm infants.

Deregulation of vascular endothelial growth factor (VEGF) levels leads to retinopathy of prematurity (ROP). Vitamin D (VIT-D) is known to regulate VEGF in an oxygen dependent manner. The purpose of this study was to correlate tear levels of VEGF and VIT-D with different ROP stages in preterm infants. In this prospective cross-sectional study, we enrolled 104 pre-term infants. They were grouped into: Group-1 (Classical ROP) and Group-2 (Aggressive ROP), which were further subdivided into Group-1A (progressing), Group-1B (regressing), Group-2A (pre-treatment), and Group-2B (post-treatment). Tear VEGF and VIT-D levels and their association with different ROP stages were assessed. Stage 1 and stage 2 had higher whereas stage 3 had lower VEGF levels in Group-1B compared to Group-1A. Stage 1 and stage 3 showed higher levels of VIT-D with no difference in stage 2 in Group-1B compared to Group-1A., Group-2B showed higher VEGF and lower VIT-D levels compared to Group-2A. Presence of a positive correlation at an early stage (stage 1) of ROP and a negative correlation at a more advanced stage (stage 3) of ROP with VIT-D and VEGF implies stage-specific distinct signaling crosstalk. These findings suggest that VIT-D supplementation may have the potential to modify the course and outcome of ROP.

Serial ERG monitoring of response to therapy in vitamin A deficiency related night blindness.

Two male patients with known systemic disorders who presented with complaints of nyctalopia underwent a complete ophthalmic examination including electrophysiological evaluation and serum vitamin A (retinol) levels. A significant vitamin A deficiency was detected, supplementation started and repeat electroretinogram (ERG) testing was carried out to monitor the timeline of recovery. Restoration of rod and generalised cone function was rapid within the first week of receiving treatment and near normal recovery was seen after 1 month of supplementation. Serial monitoring of ERG changes in vitamin A deficiency (VAD) associated night blindness plays an important role to demonstrate functional recovery post-treatment. The different effects of VAD on rod and cone function, and their rate of recovery, may reflect differences in the visual cycle between the two photoreceptors. We report the serial ERG changes in VAD related night blindness secondary to intestinal lipofuscinosis and liver cirrhosis in two patients.

Resveratrol Rescues Human Corneal Epithelial Cells Cultured in Hyperosmolar Conditions: Potential for Dry Eye Disease Treatment.

PURPOSE: Dry eye disease (DED) is a common ocular surface condition across age groups. Recently, vitamin D deficiency has gained importance as a causative factor, and its supplementation alleviates symptoms of DED. Resveratrol (RES) regulates vitamin D receptors (VDRs) and Notch signaling. We investigated the role of RES on vitamin D levels and Notch signaling under hyperosmolar conditions. METHODS: Human corneal epithelial (HCE-T) cells were treated with RES in hyperosmolar and normal conditions. Quantitative real-time polymerase chain reaction (PCR), immunofluorescence, enzyme-linked immunosorbent assay, and western blot analysis were performed for estimating reactive oxygen species, VDR, secreted 25-hydroxyvitamin D3, and Notch signaling pathway molecules in treated and control cells. RESULTS: HCE-T cells in hyperosmolar conditions had increased reactive oxygen species levels and decreased vitamin D levels that got restored in the presence of RES. Hyperosmolarity also reduced VDR expression and Notch activity that normalized to original levels with RES. In the presence of Notch blocker LY-411575, RES could not restore VDR expression or secreted vitamin D levels in HCE-T cells exposed to hyperosmolar conditions, whereas recombinant Jagged1 restored vitamin D and VDR levels. CONCLUSIONS: RES restores vitamin D levels in hyperosmolar conditions most likely through activation of Notch signaling. Hence, RES can be a potential adjuvant in DED for patients considered for vitamin D treatment.

Vitamin-D3 (α-1, 25(OH) 2D3) Protects Retinal Pigment Epithelium From Hyperoxic Insults.

Purpose: Oxidative stress affects the retinal pigment epithelium (RPE) leading to development of vascular eye diseases. Cholecalciferol (VIT-D) is a known modulator of oxidative stress and angiogenesis. This in vitro study was carried out to evaluate the protective role of VIT-D on RPE cells incubated under hyperoxic conditions. Methods: Cadaver primary RPE (PRPE) cells were cultured in hyperoxia (40% O2) with or without VIT-D (α-1, 25(OH) 2D3). The functional and physiological effects of PRPE cells with VIT-D treatment were analyzed using molecular and biochemical tools. Results: Vascular signaling modulators, such as vascular endothelial growth factor (VEGF) and Notch, were reduced in hyperoxic conditions but significantly upregulated in the presence of VIT-D. Additionally, PRPE conditioned medium with VIT-D induced the tubulogenesis in primary human umbilical vein endothelial cells (HUVEC) cells. VIT-D supplementation restored phagocytosis and transmembrane potential in PRPE cells cultured under hyperoxia. Conclusions: VIT-D protects RPE cells and promotes angiogenesis under hyperoxic insult. These findings may give impetus to the potential of VIT-D as a therapeutic agent in hyperoxia induced retinal vascular diseases.

Possible Role of Sildenafil Citrate in the Recurrence of Neovascularization in Laser-regressed Aggressive Posterior ROP.

BACKGROUND: Systemic diseases and their treatment influence aggressive posterior retinopathy of prematurity. CASE CHARACTERISTICS: A premature infant with aggressive posterior retinopathy of prematurity underwent laser treatment with a favourable outcome. She was started on oral sidenafil citrate for pulmonary hypertension. Ten days later she developed neovascularization within the lasered retina. INTERVENTION/OUTCOME: Considering the possible role of sildenafil in this unusual development, the drug was withdrawn resulting in regression of the neovascularization. MESSAGE: The clinician should be aware of this retinal adverse effect of sildanefil in neonates with aggressive posterior retinopathy of prematurity.

Monitoring neovascularization in aggressive posterior retinopathy of prematurity using optical coherence tomography angiography.

We describe the use of optical coherence tomography angiography (OCTA) in detecting and monitoring regression of the neovascular complex (NVC) in a case of aggressive posterior retinopathy of prematurity (AP-ROP). A premature Asian Indian girl with AP-ROP underwent laser photoablation at 26 days of life. Persistent NVC at the posterior border of the lasered retinal bed was detected clinically. On en face spectral domain optical coherence tomography (SD-OCT) and OCTA, the NVC appeared as an arborizing vascular net in the superficial capillary plexus. The deep capillary plexus and outer retinal layers showed corresponding flow outlines that suggested deeper extensions of the lesion. Supplemental laser treatment of the NVC was performed. Ten days later repeat en face SD-OCT and OCTA of the identical retinal location revealed that the vascular tortuosity and dilatation had reduced and that the flow lesions in the deeper layers were undetectable. Our findings in this case suggest that the NVC in AP-ROP extends beyond the superficial retina.