Effect of Lingqi Huangban granule plus intravitreal ranibizumab on macular edema induced by retinal vein occlusion: a randomized controlled clinical trial.

OBJECTIVE: To investigate the effect of Lingqi Huangban granule (LQHB) plus intravitreal ranibizumab in the treatment of macular edema (ME) induced by retinal vein occlusion (RVO). METHODS: A prospective, randomized controlled study was conducted. A total of 60 subjects with RVO induced ME were randomized into control group (CG) (30 eyes) and LQHB group (LQHBG) (30 eyes). CG patients underwent intravitreal ranibizumab (IVR) injections. LQHBG patients were treated with oral LQHB combined with IVR injections. In order to reduce the financial burden of the injections, we used one injection and pro re nata (PRN) regimen for both groups. The best-corrected visual acuity (BCVA), central macular thickness (CMT), and mean number of injections were evaluated at the beginning of treatment and 3, 6, 9 and 12 months afterward. All the subjects were followed up for 1 year. RESULTS: At the beginning of treatment, there were no statistically significant differences between the two groups in terms of the general condition of patients (P > 0.05). At 3, 6, 9 and 12 months after treatment, however, the BCVA scores improved and the CMT measurements decreased in all patients (P < 0.05), with the improvement of LQHBG significantly greater than that of CG (P < 0.05). The mean numbers of ranibizumab injections were 1.8 ± 0.3 in LQHBG and 2.3 ± 0.6 in CG, respectively (P < 0.05). No adverse events were reported in both groups. CONCLUSION: LQHB plus intravitreal ranibizumab could be a much more effective and economic treatment for stabilizing and improving vision with fewer intravitreal injections in the treatment of RVO induced ME. This integrative therapy appears to be a promising option for this type of patient.

Pharmacokinetics, pharmacodynamics and pre-clinical characteristics of ophthalmic drugs that bind VEGF.

Drugs that prevent the binding of VEGF to its trans-membrane cognate receptors have revolutionized the treatment of the most important chorioretinal vascular disorders: exudative age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. Pegaptanib, which binds to VEGF165 and longer isoforms, ranibizumab and bevacizumab, which bind all VEGF-A isoforms, and aflibercept, which binds VEGF-A, VEGF-B, and placental growth factor, all bind VEGF165 with high affinity. The drugs have relatively long half-lives (7 to 10 days) after intravitreal depot injections and clinical durations of action that usually exceed 4 weeks. Plasma VEGF concentrations decrease after intravitreal injections of bevacizumab and aflibercept because their systemic half-lives are extended by their Fc fragments. Extensive in vitro and in vivo testing shows that the drugs prevent VEGF-mediated activation of endothelial cells while exhibiting little evidence of toxicity. Further anti-VEGF drug development is on-going.

Delayed response of the retina after hyperbaric oxygen exposure.

PURPOSE: To examine retinal electrophysiological function and retinal thickness in healthy eyes before and after hyperbaric oxygen (HBO) exposure. METHODS: The healthy eye in each of six subjects who underwent experimental HBO treatment for branch retinal vein occlusion in the fellow eye was examined using multifocal electroretinography (mfERG) and optical coherence tomography (OCT) at baseline and following a course of five consecutive daily sessions of exposure to HBO at 2.4 atmospheres of absolute pressure lasting 90 min each. RESULTS: After HBO, P1 implicit times of the mfERG were significantly shorter than at baseline. The response was delayed, being undetectable on the day treatment concluded, whereas a 2.65% reduction in implicit time was seen 1 week later (p = 0.032). The P1 implicit time remained 2.49% shorter than at baseline 1 month after the end of the HBO sessions (p = 0.020). The bulk of the response to HBO was found in the foveal and parafoveal regions. No detectable change was seen in mfERG amplitudes or in the volume or thickness of the retina. CONCLUSION: A mfERG component related to bipolar and Müller cell function was accelerated by a short intermittent exposure to HBO. The response developed after the end of the HBO exposure and lasted for at least 3 weeks, suggesting that it was prompted by the withdrawal of HBO rather than the onset and subsequent brief exposure to HBO.

Video microscope recording of the dynamic course of thrombosis and thrombolysis of the retinal vein in rabbits.

PURPOSE: The purpose of this study was to investigate the dynamic course of experimental thrombosis and thrombolysis of the retinal veins. METHODS: Dynamic changes in the blood flow in the retinal veins were documented on a digital recorder through a microscope-mounted video camera and were analyzed on a monitor by video playback. Photochemical thrombus formation was induced by intravenous injection of 30% Rose Bengal followed by endoillumination of individual branch retinal veins of the eyes of 20 anesthetized pigmented rabbits. Subsequently, 10 rabbits were treated with an infusion in an ear vein of 3 mg/kg recombinant tissue plasminogen activator, whereas 10 control rabbits were administered with similar volumes of normal saline solution. Occlusion and recanalization were confirmed histologically and assessed by video microscopy. RESULTS: At the site exposed to light, photochemical injury resulted in the formation of a white thrombus, stagnation of blood flow, and subsequent complete venous occlusion in 20 rabbits. In this study, of the 10 animals in the recombinant tissue plasminogen activator treatment group, 9 (90%) showed evident thrombolysis, whereas none of the control group animals showed evident thrombolysis. The video showed that the massive thrombus disrupted into nonuniform fragments, which were quickly washed away by the blood flow, and the circulation was reestablished with no recurrence of secondary obstruction. CONCLUSION: In vivo data suggest that video microscopy may provide a visual approach for observing the dynamic changes occurring during experimental thrombus formation and lysis by the early administration of recombinant tissue plasminogen activator; this approach may assist in future investigation of thrombus research of ocular fundus.

Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma.

Glaucoma is one of the major neurological disorders in eye leading to irreversible blindness in elderly. Increase in intraocular pressure (IOP) has been considered to be the major risk factor for the progressive loss of retinal ganglion cells (RGCs) in retina. While attenuation of IOP has been a major pharmaceutical target, reduction of IOP cannot prevent progressive loss of RGCs. In this regard, urgent need for alternative treatment has to be investigated. Anti-aging medicinal herb Lycium barbarum L. has been used for centuries in Eastern World to protect the eyes and maintain good health. Using an ocular hypertension (OH) model in rat by laser photocoagulation of episcleral and limbal veins, we attempted to investigate whether L. barbarum can promote RGCs survival against elevated IOP. Oral administration of L. barbarum in Sprague-Dawley rats (250-280 g) significantly reduced the loss of RGCs, although elevated IOP was not significantly altered. Rats fed with the 1 mg/kg extract could nearly totally escape from pressure-induced loss of RGCs. In conclusion, this is the first in vivo report showing the therapeutic function of L. barbarum against neurodegeneration in the retina of rat OH model. The results demonstrate that this extract may be a potential candidate for the development of neuroprotective drug against the loss of RGCs in glaucoma.

[Effect of Panax notoginseng saponins combined isovolumic haemodilution on the retinal microcirculation of patients with retinal vein occlusion].

OBJECTIVE: To study the effect of Panax notoginseng saponins (PNS) or isovolumic haemodilution (IHD) and combination of PNS with IHD on retinal microcirculation of patients with retinal vein occlusion (RVO). METHOD: Seventy three patients with RVO were allocated at random to three groups which were treated with PNS, IHD, or PNS + IHD respectively. The retinal circulation time (RCT) and retinal hemorrhage, edema, leakage of capillary, cystoid macular edema (CME), and nonperfusion area of capillary in retina were observed before and after treatment. RESULT: RCT of patients with RVO was shortened by three treating methods. RCT in the patients who treated by PNS + IHD was the shortest, especially in the patients with nonischemic RVO and branch retinal vein occlusion(BRVO). The retinal hemorrhage, edema, leakage of capillary, and CME in the patients treated by PNS + IHD disappeared quicker than those treated by PNS or IHD. At the same time, the incidence of nonperfusion area in patients whose course of disease was shorter than fourteen days was decreased. The perfusion of capillaries was increased at the edge of nonperfusion area which existed before the treatment. But the effect for nonperfusion area which existed before the treatment in the type of ischemic RVO was not obvious. CONCLUSION: The treatment of PNS + IHD can both shorten RCT of patients with RVO, and promote absorption of retinal hemorrhage, edema, leakage of capillary, and CME. It is possible that PNS + IHD treatment also has an effect to decrease the forming of nonperfusion area in patients whose course of disease is at early stage.

Venous collateral remodeling in a patient with posttraumatic glaucoma.

PURPOSE: To photographically document venous collateral development, remodeling, and regression in a patient with traumatic glaucoma. METHODS: Consecutive fundus photographs were evaluated, labeled, and correlated with the clinical history of a patient with unilateral posttraumatic glaucoma. RESULTS: This report photographically documents the appearance, remodeling, and subsequent disappearance of collateral vessels from venous occlusion on the surface of the optic disk in an eye with increased intraocular pressure and progressive glaucomatous cupping. CONCLUSIONS: Asymptomatic chronic obstruction of a branch retinal vein on the optic disk may cause venous collaterals to develop in the absence of retinal hemorrhages or other signs of venous occlusive disease. Increased intraocular pressure, arteriolarsclerosis, and glaucomatous cupping are risk factors for these occlusions.

Hyperbaric oxygen treatment for macular edema in retinal vein occlusion: relation to severity of retinal leakage.

Twelve subjects with macular edema in retinal vein occlusion received hyperbaric oxygen treatment. Median visual acuity improved from 20/100 to 20/25 (p = 0.002). Clinically significant improvement (2 lines or more) was achieved in 10 cases (83%). Evaluation of the inward permeability coefficient of the blood-retinal barrier using vitreous fluorophotometry showed no significant alteration in the permeability. Studies of larger groups of vein occlusion patients are required to better understand and characterize the visual changes after the oxygen treatment. Moreover, further follow-up is required before conclusions can be reached about the long-term effect of this treatment.

[Hyperbaric oxygen treatment for macular edema after retinal vein occlusion--fluorescein angiographic findings and visual prognosis].

It has been reported that hyperbaric oxygen treatment improves visual function in patients with chronic macular edema associated with retinal vein occlusion. This study was designed to investigate relationship between visual prognosis and characteristics of macular edema. From fluorescein angiography performed prior to the therapy, areas of capillary closure and fluorescein leakages were quantitatively evaluated within 1 disc diameter from the fovea. In 27 eyes for which good angiograms were available, 19 eyes were classified as having mild ischemia 1 (area of capillary closure < 25%) and 8 eyes were classified as having severe ischemia (closure area < or = 25%). Of the 27 eyes, 14 showed visual improvement after the therapy. While only one eyes (13%) had visual improvement in the severe ischemic group, 11 eyes (58%) showed visual improvement in the mild ischemic group. The degree of fluorescein leakage before the therapy had no effect on visual outcome. The degree of macular ischemia was found to be a more significant factor influencing visual prognosis after the treatment than the degree of macular edema.

[The modality of Huoxue-Huayu in treatment of retinal vein occlusion].

80 patients with retinal vein occlusion were randomly divided into 2 groups A and B to be treated with Fundus-III (a composite herbal recipe for Huoxue-Huayu or invigoration of blood circulation and reduction of blood stasis) and urokinase respectively for 1 month. The visual acuity in group A was remarkably improved while that in group B did not change. The extravasated retinal blood was evidently absorbed in 92.7% of the cases in group A and in 66.7% of those in group B, the difference being significant. Fundus-III also improved the retinal circulation, decreased the whole blood viscosity and fibrinogen content, and reduced leakage of the retinal capillaries. The total effective rates were 83.7% in group A and 58.7% in group B, with significant statistical difference between the 2 groups (P < 0.01).

Retinal leakage in retinal vein occlusion: reduction after hyperbaric oxygen.

A 54-year-old woman with a history of bilateral central retinal vein occlusion, probably due to an inflammatory process, developed a hemispheric retinal vein occlusion with cystoid macular edema in her only seeing eye. Five months later, in the absence of improvement in vision and macular edema, she received on two occasions a 2-weekly course of twice daily 100% hyperbaric oxygen. After each course retinal leakage, as assessed by vitreous fluorophotometry, decreased from abnormal to the normal range while visual acuity improved by two lines. The possible implications are discussed.