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.

Minimum Corneal Diameter and Anterior Steep Axis Curvature Share the Same Meridian: A Novel Finding.

PURPOSE: To define the external scleral sulcus (ESS) on a Scheimpflug image and use it for a morphometric analysis of corneal diameter (CD). DESIGN: Retrospective, cross-sectional study of pediatric Asian-Indian eyes. METHODS: One random eye of 353 subjects between 5 and 18 years underwent 25-scan Pentacam HR imaging. For all scans, densitometry values along the anterior corneal edge were recorded and differentiated. The peaks on the differentiated curve were chosen as the ESS points, and this distance between them was called CD. Vertical (vCD), maximum (maxCD), minimum (minCD) CD and their meridians were defined. Multiple regression models (MRMs) with CD and other Pentacam parameters were built to predict astigmatism and its axis, mean keratometry (Kmean), and Belin/Ambrósio enhanced ectasia display deviation (BAD-D). MRMs were validated using intraclass correlation coefficient (ICC). Estimated horizontal CD (hCD) was validated against digital caliper measurement using ICC. RESULTS: The ICC (95% CI) between caliper and hCD was 0.96 (0.93, 0.97). MRM predictions (P < .001) used CD parameters, anterior chamber depth, corneal volume and distance from the corneal thinnest location to apex. These predictions achieved an ICC of 0.34 (0.18, 0.46), 0.82 (0.78, 0.86), 0.87 (0.84, 0.89), and 0.81 (0.76, 0.84), respectively. The astigmatism axis prediction depended on the minCD and maxCD meridians. Its within-subject SD (4.97°) was less than 2 consecutive Pentacam scan angles (7.2°). CONCLUSIONS: The CD metric strongly correlated with the astigmatism axis, keratometry, and BAD-D. Its spatial description may be significant in corneal treatment planning and disease diagnoses.

Vitamin D and eye: Current evidence and practice guidelines.

Vitamin D is a steroid hormone that has widespread role in human physiology, not only in the maintenance of calcium homeostasis but also in immunomodulation, cellular differentiation, and proliferation. The immunomodulatory effects of vitamin D are well known and are applicable to the ocular surface immune cells and structural cells. The role of vitamin D in ocular surface conditions such as dry eye disease (DED), keratoconus (KC), and post-surgical outcomes has received widespread and well-deserved attention. Vitamin D supplementation is shown to improve DED clinically as well as in experimental models. The anti-inflammatory properties may be crucial in the treatment of ocular surface conditions such as DED and KC. Vitamin D plays a multifaceted role in corneal wound healing with its anti-inflammatory and extracellular matrix remodeling properties. In this review, we discuss how to approach patients with DED and those undergoing refractive surgery with the available basic and clinical knowledge on the role of vitamin D in these conditions. We aim to highlight the importance of clinically harnessing vitamin D-mediated natural immuno-inflammatory modulation in combination with currently available standard of care strategies to reduce the morbidity and disease duration associated with ocular surface diseases.

A randomized controlled study evaluating outcomes of intense pulsed light and low-level light therapy for treating meibomian gland dysfunction and evaporative dry eye.

Purpose: This randomized, controlled, blinded study evaluates the efficacy of intense pulsed light (IPL) therapy with low-level light therapy (LLLT) in the treatment of meibomian gland dysfunction (MGD) and evaporative dry eye (EDE) compared to a control group. Methods: Hundred patients with MGD and EDE were randomized into control (50 subjects, 100 eyes) and study group (50 subjects, 100 eyes). The study group underwent three sittings of IPL with LLLT 15 days apart and were followed up 1 month and 2 months after the last treatment sitting. The control group underwent sham treatment and was followed up at the same intervals. The patients were evaluated at baseline and 1 month and 3 months (post 1st treatment) for dry eye. Schirmer's test and tear breakup time (TBUT), OSDI, meibomian gland expression, and meibography. Results: The study group showed significant improvement in OSDI scores (P < 0.0001) compared to the control group and a significant improvement in TBUT (P < 0.005) compared to the control group. There was no change in schirmer's test and an improvement in the meibomian gland expression but not significant. Conclusion: The results show that a combined therapy of IPL with LLT is effective in treating MGD with EDE compared to controls, and repeated treatment sessions have a cumulative effect on the disease outcomes.

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.

Clinical and Molecular Outcomes After Combined Intense Pulsed Light Therapy With Low-Level Light Therapy in Recalcitrant Evaporative Dry Eye Disease With Meibomian Gland Dysfunction.

PURPOSE: Dry eye disease (DED) is a leading cause of ocular morbidity worldwide. This study evaluates the effects of combined light therapy [intense pulsed light (IPL) and low-level light therapy (LLLT)] on clinical and molecular outcomes in evaporative DED with meibomian gland dysfunction (MGD). METHODS: This prospective study evaluated 94 eyes (47 subjects) with chronic MGD treated with combined light therapy. Patients underwent a detailed evaluation of MGD and DED using the Ocular Surface Disease Index, dry eye tests-tear breakup time and Schirmer test, ocular surface staining, meibomian gland expressibility scoring, and meibography. Patients underwent a single session of combined light therapy (IPL + LLLT treatment) using the Eye-light device. All these tests were repeated at 3 and 6 months after treatment. Tear fluid and ocular surface wash samples were collected from a subset of patients before and after treatment for cellular and secreted immune factor profiling by flow cytometry. RESULTS: Combined light therapy (IPL + LLLT) demonstrated a marked improvement in the clinical metrics studied. Three months after treatment, Ocular Surface Disease Index showed a significant reduction in 95.6% ( P < 0.0001), tear breakup time increased in 72.3% ( P < 0.0001), and meibomian gland expressibility scoring increased in 80.8% ( P < 0.0001) of the eyes. These effects were observed to be sustained during the 6-month follow-up visit. Significant ( P < 0.05) reduction in tear fluid levels of interleukin-1ß, interleukin-17F, and MMP9; MMP9/TIMP1 ratio; and ocular surface B-cell proportions was observed. CONCLUSIONS: Combined light therapy shows promising results in patients with chronic MGD and DED, even in recalcitrant cases. Clinical and molecular factor alterations support the improved symptomatology and reduced inflammation.

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.

Management of Ocular Neuropathic Pain With Vitamin B12 Supplements: A Case Report.

PURPOSE: To report the case of a 28-year-old patient with persistent bilateral burning pain and foreign body sensation in both eyes for the past 1 year. The patient showed a poor response to 0.05% cyclosporine eye drops and frequent instillations of artificial tears. Ocular examination showed few superficial punctate epithelial defects, well-positioned laser in situ keratomileusis (performed 5 years ago with symptomless recovery) flaps, and clear interfaces bilaterally, with a tear film breakup time of 7 and 8 seconds in the right and left eyes, respectively. The results of Schirmer tests, confocal microscopy, corneal esthesiometry, and meibography were normal for both eyes. The patient was incidentally diagnosed with vitamin B12 deficiency, with a serum vitamin B12 value of 90 pg/mL (reference range, 236-911 pg/mL), during routine laboratory tests. In view of weak correlation between signs and symptoms, a putative diagnosis of ocular neuropathic pain secondary to vitamin B12 deficiency was made. METHODS: Case report. RESULTS: The patient was treated with parenteral vitamin B12, and topical therapy was continued without any changes. The patient experienced dramatic improvement with a decrease in symptoms within 3 weeks of administering vitamin B12 supplements and was symptom-free in the absence of any topical medication 6 months after treatment. CONCLUSIONS: Vitamin B12 deficiency, although common in India, has not been reported to be associated with ocular symptoms, including pain and mimicking those seen in severe dry eye. Vitamin B12 deficiency should be considered in the differential diagnosis of ocular neuropathic pain and dry eye in patients presenting with recalcitrant ocular neuropathic pain.

Topical podophyllum-induced toxic anterior uveitis.

OBJECTIVE: To report a case of toxic anterior uveitis probably secondary to the use of topical podophyllum. DESIGN: Case report, interventional. METHODS: The authors present a 78-year-old male with acute anterior uveitis that developed within a couple of hours of application of topical podophyllum. In vivo confocal microscopy showed unique findings that disappeared following treatment with topical steroids alone. The patient reapplied podophyllum 2 months later and a recurrence of uveitis was noted. RESULTS: A score of 7 was obtained using the adverse drug reaction probability scale, suggesting that the anterior uveitis is a probable adverse reaction to topical podophyllum. CONCLUSIONS: Anterior uveitis may occur after topical application of podophyllum.