Short-Term Omega-3 Supplementation Modulates Novel Neurovascular and Fatty Acid Metabolic Proteome Changes in the Retina and Ophthalmic Artery of Mice with Targeted Cyp2c44 Gene Deletion.

Cytochrome P450 (CYP) gene mutations are a common predisposition associated with glaucoma. Although the molecular mechanisms are largely unknown, omega-3 polyunsaturated fatty acids (ω-3 PUFA) and their CYP-derived bioactive mediators play crucial roles in the ocular system. Here, we elucidated the proteome and cell-signalling alterations attributed to the main human CYP2C gene deficiency using a homologous murine model (Cyp2c44-/-), and unravelled the effects of acute ω-3 PUFA supplementation in two ocular vascular beds comprising the retrobulbar ophthalmic artery (OA) and retina (R). Male Cyp2c44-/- mice (KO) and their floxed littermates (WT) were gavaged daily for 7 days with 0.01 mL/g of ω-3 PUFA composed of menhaden fish oil. Another group in respective strains served as vehicle-treated controls. OA and R were isolated at day 8 post-treatment (n = 9/group) and subjected to mass spectrometry (MS)-based proteomics and in silico bioinformatics analyses. Cyp2c44-/- resulted in significant detrimental proteome changes associated with compromised vascular integrity and degeneration in the OA and R, respectively. However, notable changes in the OA after ω-3 PUFA intake were associated with the maintenance of intercellular junctional and endothelial cell functions, as well as activation of the fatty acid metabolic pathway in the KO mice. Conversely, ω-3 PUFA supplementation profoundly influenced the regulation of a large majority of retinal proteins involved in the preservation of neuronal and phototransduction activities in WT mice, namely synaptophysin, phosducin and guanylate cyclase-1, while significantly abrogating degenerative processes in the KO mice via the regulation of, namely, synaptotagmin-1 and beta-crystallin B2. In gist, this study demonstrated that dietary supplementation with ω-3 PUFA for a short period of seven days regulated specific neuro-vasculoprotective mechanisms to preserve the functionality of the OA and R in the absence of Cyp2c44. The potential adjunct use of ω-3 PUFA for glaucoma therapy needs further investigation.

Selective Ophthalmic Artery Chemotherapy with Melphalan in the Management of Unilateral Retinoblastoma: A Prospective Study.

PURPOSE: To determine prospectively the efficacy and to assess potential side effects of melphalan selective ophthalmic artery chemotherapy (SOAC) as first-line treatment for unilateral retinoblastoma. DESIGN: Phase 2 nonrandomized, prospective study. PARTICIPANTS: Patients with unilateral retinoblastoma group B, C, or D of the International Classification for Intraocular Retinoblastoma (IRC). Group D eyes with massive vitreous seeding were not eligible. METHODS: Melphalan SOAC associated with diode laser thermotherapy, cryotherapy, or both at 4-week intervals (3-6 cycles). For persistent vitreous seeding, intravitreal melphalan chemotherapy also was used. MAIN OUTCOME MEASURES: The primary outcome was globe preservation rate. Secondary outcomes were tumor relapse rate, occurrence of ocular or systemic adverse events, and measurement of the dose area product (DAP). RESULTS: Between 2012 and 2017, 39 patients (39 eyes) with unilateral retinoblastoma were included prospectively. Three included patients did not receive SOAC (2 catheterization failures and 1 case of viral syndrome) and were considered failures. At diagnosis, IRC groups for the 36 treated patients were: B, n = 4 (11%); C, n = 13 (36%); and D, n = 19 (53%); median age was 21.5 months (range, 3.2-61.6 months). Median number of SOAC cycles was 3.9 (range, 1-6 cycles), and median melphalan dose was 4.9 mg/procedure. The median DAP was 1.24 Gy.cm2/procedure. Median follow-up was 63 months (range, 34-93 months). SOAC was associated with local treatments for 31 patients (86%): diode laser thermotherapy for all of them and cryotherapy or intravitreal chemotherapy for 10 (32%) and 9 patients (25%), respectively. SOAC treatment was interrupted in 5 patients because of severe ophthalmic (ptosis, n = 2; retinal ischemia, n = 2) or systemic (hypotension, n = 1) adverse events. At the cutoff date analysis, all patients were alive without metastasis. The 18-month eye preservation rate was 80% (range, 68.6%-94.6%). After a follow-up of at least 30 months, the ocular preservation rate was 69% (n = 24 preservations). CONCLUSIONS: This first prospective trial demonstrated that SOAC with melphalan alone as first-line treatment for retinoblastoma is efficient and well tolerated with no metastatic events, although ocular ischemic complications were observed.

Lutein Complex Supplementation Increases Ocular Blood Flow Biomarkers in Healthy Subjects.

Introduction: To investigate the effects of a lutein complex supplementation on ocular blood flow in healthy subjects. Materials and Methods: Sixteen healthy female patients (mean age 36.8 ± 12.1 years) were enrolled in this randomized, placebo-controlled, double-blinded, two-period crossover study. Subjects received daily an oral dose of the lutein with synergistic phytochemicals complex (lutein (10 mg), ascorbic acid (500 mg), tocopherols (364 mg), carnosic acid (2.5 mg), zeaxanthin (2 mg), copper (2 mg), with synergistic effects in reducing pro-inflammatory mediators and cytokines when administered together in combination) and placebo during administration periods. Measurements were taken before and after three-week supplementation periods, with crossover visits separated by a three-week washout period. Data analysis included blood pressure, heart rate, intraocular pressure, visual acuity, contrast sensitivity detection, ocular perfusion pressure, confocal scanning laser Doppler imaging of retinal capillary blood flow, and Doppler imaging of the retrobulbar blood vessels. Results: Lutein complex supplementation produced a statistically significant increase in mean superior retinal capillary blood flow, measured in arbitrary units (60, p = 0.0466) and a decrease in the percentage of avascular area in the superior (-0.029, p = 0.0491) and inferior (-0.023, p = 0.0477) retina, as well as reduced systolic (-4.06, p = 0.0295) and diastolic (-3.69, p = 0.0441) blood pressure measured in mmHg from baseline. Data comparison between the two supplement groups revealed a significant decrease in systemic diastolic blood pressure (change from pre- to post-treatment with lutein supplement (mean (SE)): -3.69 (1.68); change from pre- to post-treatment with placebo: 0.31 (2.57); p = 0.0357) and a significant increase in the peak systolic velocity (measured in cm/sec) in the central retinal artery (change from pre- to post-treatment with lutein supplement: 0.36 (0.19); change from pre- to post-treatment with placebo: -0.33 (0.21); p = 0.0384) with lutein complex supplement; data analyses from the placebo group were all non-significant. Discussion: In healthy participants, oral administration of a lutein phytochemicals complex for three weeks produced increased ocular blood flow biomarkers within retinal vascular beds and reduced diastolic blood pressure compared to placebo.

Severe vision loss caused by cosmetic filler augmentation: Case series with review of cause and therapy.

Hyaluronic acid (HA) injection is a popular nonsurgical, facial rejuvenating procedure. Due to the rapidly expanding use of HA injections, significant potential complications have also increased in frequency. Among these complications, the rare but most devastating one is arterial occlusion, which can result in skin necrosis or blindness. To describe the mechanisms behind vision loss secondary to hyaluronic acid injection and the efficacy of treatments to restore vision and associated ocular functionality. We reviewed six cases of patients from October 2011 to December 2017 who experienced vision loss after receiving facial HA injections and the subsequent treatments undertaken to attempt to reverse the vision loss and additional eye complications. Of the six patients, four received nose, one received forehead, and another one received temple injections. All six patients developed vision loss secondary to hyaluronic acid embolization in retinal or ophthalmic arteries. Additional complications included severe periorbital pain, ptosis, impairment of extraocular muscle functionality. Recovery of vision was dependent on the type, frequency, and duration of subsequent treatment. Vision loss is a rare but catastrophic complication caused by hyaluronic injection that occurs secondary to hyaluronic acid embolization in retinal or ophthalmic arteries due to retrograde flow from facial vascular anastomoses. We suggest the early supratrochlear/supraorbital hyaluronidase injection, ocular massage, and re-breathing into a plastic bag as safe, uncomplicated and effective methods to restore the retinal circulation and reverse vision loss.

The effects of antioxidants on ocular blood flow in patients with glaucoma.

PURPOSE: To investigate the effects of an antioxidant dietary supplement that includes Ginkgo biloba, on retinal and retrobulbar blood flow in patients with open-angle glaucoma (OAG). METHODS: Forty-five patients with confirmed OAG were enroled in a randomized, double blinded, placebo-controlled cross-over study. Baseline and postadministration measurements of intraocular pressure (IOP), ocular perfusion pressure (OPP), retrobulbar blood flow, and retinal capillary blood flow were non-invasively measured (ultrasound and laser Doppler modalities, respectively) before and one month after antioxidant nutraceuticals and placebo administration. Changes in measurements between the active supplement and placebo arms were evaluated using paired t-tests, with p < 0.05 considered statistically significant. RESULTS: Antioxidant supplementation produced a statistically significant increase in peak systolic and/or end diastolic blood flow velocities in all retrobulbar blood vessels compared to placebo. Vascular resistance was also reduced in central retinal and nasal short posterior ciliary arteries following antioxidant administration. Additionally, antioxidant supplementation increased superior and inferior temporal retinal capillary mean blood flow and the ratio of active to non-active retina capillaries compared to placebo. CONCLUSION: One-month oral administration of antioxidants produced increases in biomarkers of ocular blood flow within retinal and retrobulbar vascular beds in patients with OAG.

Successful treatment of central retinal artery occlusion using hyperbaric oxygen therapy

Central retinal artery occlusion (CRAO) is considered an ophthalmologic emergency. The prognosis of this disease is very poor. Currently, there is no generally effective therapy available to treat CRAO. Hyperbaric oxygen therapy (HBOT) can increase the volume of oxygen delivered to the ischemic retinal tissue until spontaneous or assisted reperfusion occurs. We report the case of a patient who experienced sudden visual loss due to CRAO that was treated with HBOT. The patient was an 81-year-old woman who presented with CRAO in her right eye (OD). She exhibited “hand motion” visual acuity before treatment. She underwent three sessions of HBOT at a pressure of 2.8 atmospheres absolute, performed over 3 days. After 4 days in hospital, her visual acuity improved to 0.4 (OD) for far vision and 0.5 (OD) for near vision. Her vision was stable without the supply of oxygen; therefore, she was discharged.

[Efficacy on visual display terminal syndrome treated with jingjin therapy of Zhuang medicine].

OBJECTIVE: To observe the efficacy and explore the effect mechanism on visual display terminal syndrome treated with jingjin therapy of Zhuang medicine. METHODS: Sixty-five patients of visual fatigue induced by the visual display terminal operation were treated with jingjin trigeminy therapy of Zhuang medicine, e.g. massage manipulation, acupuncture and cupping; acting on the specific stimulating areas in Zhuang medicine, relevant with orbit, temple, forehead, ear and Baihui (GV 20). Each treatment lasted 40 min, once every two or three days. Totally, 10 to 14 treatments were required. The scores of visual symptoms and the ocular hemodynamics before and after treatment were observed, and clinical effect were evaluated in the two groups. RESULTS: After treatment, the scores of visual symptoms were reduced apparently as compared with those before treatment (all P<0.05). The total effective rate was 84.6% (55/65). The peak systolic velocity (PSV), the end diastolic velocity (EDV) in anterior ciliary artery (ACA) and the central retinal artery (CRA) were improved obviously, indicating the significant differences before and after treatment (all P<0.05). CONCLUSIONS: The jingjin therapy of Zhuang medicine alleviates the visual symptoms in patients of visual fatigue and improves visual quality. The effects are related to the improvement of ocular microcirculation.

Hyperbaric Oxygen Therapy to Avoid Blindness From Filler Injection.

The most serious complication of filler or fat injection is blindness. According to a recent systematic review of 98 patients of blindness provoked by filler or fat injection, only 2 patients had the outcome of a complete recovery of vision.In the literature, only 2 papers were found in which hyperbaric oxygen therapy (HBOT) was used in ophthalmic artery obstruction. However, no improvement of vision was obtained in either patient. Recently, the authors treated a patient who had central retinal vein occlusion and cilioretinal artery occlusion with HBOT (daily 2-hour sessions at 253 kPa for 14 days), and his visual acuity returned to normal.In central retinal artery obstruction, if the cilioretinal artery is present, it will maintain the thickness of the retina to a variable extent. Though the size of the cilioretinal artery and the area it supplies varies, 36.2% (32.1-40.2%) of people have a cilioretinal artery.Thereafter, HBOT might be applied to patients with central retinal artery occlusion following filler injection.

Successful treatment of central retinal artery thromboembolism with ocular massage and intravenous acetazolamide.

A 67-year-old woman presented with left-sided headache and blurred vision, worse during hypertensive episodes. CT angiography showed a 4 mm left internal carotid artery (ICA) aneurysm incorporating the ophthalmic artery. She passed a test balloon occlusion, so the aneurysm was coil occluded, without immediate complication. Four days postprocedure she experienced sudden loss of vision in the left eye and funduscopy showed central retinal artery occlusion secondary to emboli from the coiled aneurysm. She was treated promptly with intravenous acetazolamide and ocular massage and regained full visual acuity. Thromboembolism to the eye during or after neurointerventional treatment is a relatively rare but devastating complication. This report demonstrates the effectiveness of combined intravenous acetazolamide and ocular massage in dealing with this complication when delivered promptly.

Effects of sub-Tenon's anaesthesia on ocular hemodynamics.

OBJECTIVE: To research the effects of sub-Tenon's anaesthesia (STA) on ocular hemodynamics in patients with cataract using colour Doppler imaging (CDI). DESIGN: Prospective clinical study. PARTICIPANTS: Thirty-four eyes of 34 patients with age-related cataract. METHODS: Peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) values of the ophthalmic artery (OA), central retinal artery, and central retinal vein were measured by CDI before and immediately after performing sub-Tenon block using 2 mL of 2% lidocaine with adrenaline (1:200 000). RESULTS: Both PSV and EDV values were significantly decreased after sub-Tenon injection in all the studied vessels of the patients. However, no important changes were observed in the RI values of the vessels. CONCLUSIONS: STA markedly reduced ocular blood flow. The reduction may be more acceptable compared with other retrobulbar block methods. Sub-Tenon block should be performed carefully to senile patients with cataract with vascular occlusive disorder.

Indocyanine green enhanced transpupillary thermotherapy in combination with ophthalmic artery chemosurgery for retinoblastoma.

PURPOSE: Review our experience in the use of indocyanine green (ICG) enhanced transpupillary thermotherapy (TTT) in combination with ophthalmic artery chemosurgery for retinoblastomas unresponsive to standard TTT. METHODS: Single centre, retrospective study of 16 eyes in 13 retinoblastoma patients treated with TTT and ICG via indirect ophthalmoscope: 23 treatments of 16 eyes, with a mean follow-up of 12.1 months (range 3-35 months). Outcome measures included tumour response and electroretinogram. RESULTS: Treatment resulted in significant tumour regression in all eyes: 13 eyes with well-differentiated characteristics, 2 with implanting vitreous seeds and 1 eye refractory to traditional TTT. ERG function was retained in all eyes. CONCLUSIONS: ICG-enhanced TTT with ophthalmic artery chemosurgery can effectively treat retinoblastoma refractory to conventional focal treatments without deleterious ocular side effects.

Does phacoemulsification under topical anesthesia affect retrobulbar blood flow?

PURPOSE: To investigate with color Doppler imaging the effects of phacoemulsification surgery under topical anesthesia on retrobulbar vessels hemodynamics. METHODS: In this prospective study, color Doppler imaging was used to measure the maximum (Vmax) and minimum flow velocity (Vmin) of the central retinal vein, and the Vmax and Vmin, pulsatility index and resistance index of the central retinal artery, nasal, and temporal posterior ciliary arteries, and ophthalmic artery blood flow before and 1 day after phacoemulsification surgery under topical anesthesia. RESULTS: After phacoemulsification surgery under topical anesthesia, Vmin of the central retinal artery increased (p ≤ 0.05), whereas the other variables showed no significant change. CONCLUSIONS: Phacoemulsification surgery under topical anesthesia has a minor effect on retrobulbar blood flow. Therefore topical anesthesia should be suitable for patients with ocular perfusion disorders (eg, glaucoma).

Transarterial embolization of a high-flow maxillary arteriovenous malformation fed by multiple arteries.

A high-flow maxillary arteriovenous malformation fed by multiple arteries, including bilateral internal maxillary arteries and ophthalmic artery, is reported. A combination of polyvinyl alcohol particles and N-butyl-cyanoacrylate mixed with lipiodol was progressively deposited within the distal vascular bed by transarterial superselective embolization of the branches of bilateral internal maxillary arteries, resulting in complete anatomic and clinical cure. The authors feel that this approach is more secure and effective compared with transfemoral venous embolization and direct transosseous puncture. It also avoids mutilating surgery.

Retinal artery embolization during carotid angioplasty and carotid artery stenting: case report.

A 69-year-old man presented with a rare case of retinal artery embolization, which occurred as a complication of carotid angioplasty and carotid artery stenting performed for recurrent cerebral infarction. Magnetic resonance imaging and angiography showed right internal carotid artery stenosis with ulceration. Carotid angioplasty and carotid artery stenting were performed using the distal protection system with the PercuSurge GuardWire. However, just after dilation, the patient complained of ocular pain and blurred vision on the right, which was subsequently diagnosed as retinal artery embolization. Heparin was given for 15 hours after stenting, and aspirin and ticlopidine medication were continued. The patient received hyperbaric oxygen therapy for 1 week. The patient's blurred vision gradually improved, but visual field defect remained. Debris was probably flushed into the external carotid artery, and passed through an anastomosis into the ophthalmic artery, resulting in retinal artery embolization.

Clinical evaluation of the neuroprotective effect of alpha-tocopherol against glaucomatous damage.

PURPOSE: To evaluate the vasoregulatory effect of antioxidant alpha-tocopherol on retina via protein kinase C pathway. METHODS: Thirty glaucomatous patients (60 eyes) were included in this study. The patients were divided into three groups. For patients in Group A, tocopherol was not supplemented in their therapy. Patients in Groups B and C received 300 and 600 mg/day of oral alpha-tocopherol acetate, respectively. The ultimate blood tocopherol levels were confirmed via high-performance liquid chromatography assay. Progression of the disease for each subject was monitored via visual field measurements and color Doppler imaging of ophthalmic and posterior ciliary arteries at the beginning and at the 6th and 12th months of this study. RESULTS: The average differences between the pulsatility indexes (PI) and resistivity indexes (RI) of both ophthalmic arteries (OA) and posterior ciliary arteries (PCA) of Groups B and C were significantly lower than those of Group A at months 6 and 12. In trial groups, RI decreases observed in PCAs at months 6 and 12 and PI decreases observed in OAs at the 6th month were statistically significant. Differences of mean deviations with visual fields in Groups B and C were highly significantly lower than that of Group A. CONCLUSIONS: Alpha-tocopherol deserves attention beyond its antioxidant properties for protecting retina from glaucomatous damage.

Confirmation of blood flow in perforating arteries using fluorescein cerebral angiography during aneurysm surgery.

OBJECT: The authors performed fluorescein cerebral angiography in patients after aneurysm clip placement to confirm the patency of the parent artery, perforating artery, and other arteries around the aneurysm. METHODS: Twenty-three patients who underwent aneurysm surgery were studied. Aneurysms were located in the internal carotid artery in 12 patients, middle cerebral artery in six, anterior cerebral artery in three, basilar artery bifurcation in one, and junction of the vertebral artery (VA) and posterior inferior cerebellar artery in one. After aneurysm clip placement, the target arteries were illuminated using a beam from a blue light-emitting diode atop a 7-mm diameter pencil-type probe. In all patients, after intravenous administration of 5 ml of 10% fluorescein sodium, fluorescence in the vessels was clearly observed through a microscope and recorded on videotape. RESULTS: The excellent image quality and spatial resolution of the fluorescein angiography procedure facilitated intraoperative real-time assessment of the patency of the perforating arteries and branches near the aneurysm, including: 12 posterior communicating arteries; 12 anterior choroidal arteries; four lenticulostriate arteries; three recurrent arteries of Heubner; three hypothalamic arteries; one ophthalmic artery; one perforating artery arising from the VA; and one posterior thalamoperforating artery. All 23 patients experienced an uneventful postoperative course without clinical symptoms of perforating artery occlusion. CONCLUSIONS: Because the fluorescein angiography procedure described here allows intraoperative confirmation of the patency of perforating arteries located deep inside the surgical field, it can be practically used for preventing unexpected cerebral infarction during aneurysm surgery.

A case report of Wyburn-Mason syndrome and review of the literature.

INTRODUCTION: Wyburn-Mason syndrome is a distinct congenital neurocutaneous entity comprised of ipsilateral arteriovenous malformations (AVMs) of the midbrain, vascular abnormalities affecting the visual pathway, and facial nevi. METHODS: We report a case and review of the literature of all other reported cases of Wyburn-Mason syndrome (n = 26) in the English literature since 1973. RESULTS: In this review, we report on a 4(1/2)-year-old boy with Wyburn-Mason syndrome who presented with left retinal and orbital AVMs and a ruptured thalamic AVM. The patient did not respond to light in the left eye and demonstrated a left afferent pupillary defect. He did not have any cutaneous lesions. We also characterize other reported cases of Wyburn-Mason syndrome. CONCLUSION: The presentation of patients with Wyburn-Mason syndrome can vary greatly according to the site and the extent of vascular lesions. Intracranial AVMs occasionally hemorrhage with significant morbidity. Treatment is controversial, and patients are typically managed conservatively by observation.