Medical Retina

F. Bandello, G. Querques

• Editore: S. Karger
• Anno: 2012
• ISBN:
  9783805599917
• Argomento: Medicine
• Categoria: Opthalmology & Optometry

In the new book series ESASO Course Series, the essentials of the courses of the European School for Advanced Studies in Ophthalmology (ESASO) are made available to interested ophthalmologists, optometrists, technicians and residents all over the world. In this first volume, the seminars on retina presented by renowned experts during ESASO's activities are collected. The authors have incorporated their personal experience and full teaching acumen in their respective chapters. The topics range from molecular biology, to state-of-the-art diagnostic techniques and the newest medical treatment options.This book provides the ophthalmologist with the most recent data and evidence-based medicine on medical retina, and includes multiple areas still under debate. Because of its highly specific and updated information, focusing on the pathogenesis and management of retinal diseases, this publication is a must to all retina specialists.

Bandello F, Querques G (eds): Medical Retina.
ESASO Course Series. Basel, Karger, 2012, vol 1, pp 111-119

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Retinal Venous Occlusions: Diagnosis and Choice of Treatments

Jose Garcia-Arumi^a,b· Josep Badal^b· Miguel Zapata^b· Ana Boixadera^b· Vicente Martinez Castillo^b

^aInstituto de Microcirurgia Ocular and ^bDepartment of Ophthalmology, Hospital Vall Hebron, Barcelona, Spain

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Abstract

Retinal vascular occlusive disorders constitute one of the major causes of blindness and impaired vision. There is marked controversy on their pathogeneses, clinical features and particularly their management. Different medical and surgical approaches stated on evidence-based medicine are set out in this chapter.

Copyright © 2012 S. Karger AG, Basel

Central Retinal Vein Occlusion

Introduction

Central retinal vein occlusion (CRVO) is the third most common blinding vascular retinal disorder after diabetic retinopathy and branch retinal vein occlusion [1, 2].

Among patients with CRVO, 34% develop capillary nonperfusion and retinal ischemia. Iris neovascularization (INV) and neovascular glaucoma may occur in 45-85% of the eyes affected by ischemic CRVO and only in 5% of the nonischemic eyes [2, 3]. The main known risk factors of CRVO are hypertension and open-angle glaucoma [2-5].

The pathogenesis of CRVO is yet not very well understood. It is thought to be a compartment syndrome, since in a 1.5-mm-diameter area, the central retinal artery, the central retinal vein, and the optic nerve coexist. Thrombotic occlusion is thought to develop as the result of an increase in the arterial diameter, changes in the scleral ring, and the presence of anatomical anomalies and possible systemic factors, which together cause a decrease in the venous lumen, increased turbulence, damage to endothelium and thrombus formation. This is supported by histologic studies that localize the thrombus in the lamina cribosa in most or all cases [6, 7].

It is clear from the Central Vein Occlusion Study (CVOS) [8] that, when left to follow its natural course, the vision in patients with CRVO will most likely worsen or remain unchanged and that those patients with poor vision initially have little hope of significant spontaneous recovery. There is no known effective treatment for CRVO. Numerous treatments are available, including panretinal laser photocoagulation (PRP), grid macular laser photocoagulation, chorioretinal anastomosis (CRA) via high-intensity laser photocoagulation, and intraocular injections of drugs, with varying degrees of effectiveness and complication rates. One surgical procedure that has been developed is termed radial optic neurotomy (RON). PRP has only been effective in managing neovascular complications, and grid macular laser photocoagulation only decreases macular edema without increasing the final VA [1, 8, 9].

Pharmacologic Treatment: rTPA

Thrombolytic agents have been proposed as a treatment against a suspected thrombus in the central retinal vein. Recombinant tissue plasminogen activator (r-tPA) is a synthetic fibrinolytic agent that converts plasminogen to plasmin and destabilizes intravascular thrombi. Recombinant tissue plasminogen activator, as therapy against CRVO, has been administered by several routes: systemic [10, 11], intravitreal [12-15], and endovascular cannulation of retinal vessels, which involves cannulation of retinal vessels, either through a neuroradiologic or a vitreoretinal approach, and delivery of minute quantities of r-tPA directly to the occluded vessels to release the suspected thrombus [16, 17]. Bynoe and Weiss [18] have reported their technique of PPV followed by cannulation of a branch vein and, with the aid of a stabilization arm, injecting a bolus (average 3.4 ml) of 200 µg/ml r-tPA towards the optic nerve head. This was a pilot study with no more evidence data suggesting benefit from this technique.

Intraocular Corticosteroids

The role of corticosteroids has been explored in CRVO with particular interest to improve visual acuity by reducing macular edema. The exact mechanism of action of corticosteroids in modulating retinal edema is unknown, but it is believed that a combination of anti-inflammatory effects with modulation of cytokine and growth factor production and stabilization of the blood-retinal barrier with reduction in vascular permeability may be involved. There is little evidence for using oral corticosteroids to treat macular edema from CRVO. Several reports from intravitreal triamcinolone for CRVO macular edema have been published [19], showing initial improvement but with no longer benefit after a 1-year period. High incidences of cataract (63%) and glaucoma (30%) have also been reported as complications from intravitreal triamcinolone.

The most important study in this area is the SCORE study report 5 [20]. The first multicenter randomized clinical trial with 271 participants. The study compares the efficacy and safety of 1-and 4-mg doses of preservative-free intravitreal triamcinolone with observation in eyes with vision loss associated with macular edema secondary to perfused CRVO. Retreatment was done if necessary every 4 months. With a mean of 2.2 injections, at month 12 gain in visual acuity was found in 7, 27 and 26% of the patients, respectively. More eyes in the 4-mg triamcinolone group (35%) initiated IOP-lowering medication through 12 months compared with the 1-mg triamcinolone (20%) and observation groups (8%). Among eyes that were phakic at baseline, the estimate through month 12 of new-onset lens opacity or progression of an existing opacity in the observation group was 18% compared with 26 and 33% for the 1- and 4-mg triamcinolone groups, respectively.

This study concludes that intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO. The 1-mg dose has a safety profile superior to that of the 4-mg dose.

A phase III study for intravitreal dexamethasone drug delivery system compared 350 µg, 700 µg and sham injection, with 1,267 patients involved. Dexamethasone is a potent, water-soluble corticosteroid that can be delivered to the vitreous cavity by the dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan, Inc., Irvine, Calif., USA). A DEX implant is composed of a biodegradable copolymer of lactic acid and glycolic acid containing micronized dexamethasone. The drug-copolymer complex gradually releases the total dose of dexamethasone over a series of months after insertion into the eye through a small 22-gauge pars plana puncture using a customized applicator system. The percentage of eyes with a 15-letter improvement in BCVA was significantly higher in both DEX implant groups compared with sham at days 30 to 90, but not significant at 180 days. Percentage of DEX implant-treated eyes with intraocular pressure of 25 mm Hg peaked at 16% at day 60 (both doses) and was not different from sham by day 180. There was no significant between-group difference in the occurrence of cataract or cataract surgery [21]. Additionally, several modes of delivery are being evaluated in the preclinical and clinical trial setting to determine safety and efficacy. The iluvien sustained-release fluocinolone acetonide device (Alimera Sciences) is an injectable, nonbiodegradable, intravitreal insert designed for sustained release of the corticosteroid fluocinolone acetonide for up to 36 months. The drug is injected through a 25-gauge inserter needle. There are two intravitreal triamcinolone acetonide implants under study: the Ivation (SurModics, Inc.) and the Verisome delivery system (Icon Biosciences, Inc.). The Cortiject implant (NOVA63035, Novagali Parma) is a preservative and solvent-free emulsion that contains a tissue-activated proprietary corticosteroid prodrug that is activated at the level of the retina once released. For several years, repeated intravitreal injections of non-FDA approved triamcinolone acetonide have been used for this disease. These new sustained-release delivery-systems may provide better side-effect profiles and reduce the need for repeated intravitreal injections.

Anti- VEGF Drugs

Following CRVO subsequent hypoxia leads to upregulation of vascular endothelial growth factor (VEGF), resulting in increased retinal capillary permeability and leakage of fluid and blood into the intraretinal space. In addition, VEGF is a key promoter of angiogenesis, potentially contributing to the development of the neovascularization associated with CRVO. Antiangiogenic drugs may decrease vascular permeability and also the macular edema. Bevacizumab has been the most studied drug in this disease. Good safety and effectiveness in short-term outcomes with this drug have been reported. Main limitations of this treatment modality are its short-term effectiveness and high recurrence rate [22-24].

Ranibizumab is the other drug studied for CRVO. In a prospective study [CRUISE study, 25] 392 participants were evaluated in 3 groups (0.3 mg, 0.5 mg or sham injection every month). At 6 months, gain in visual acuity was found in 46.2, 47.9 and 16.9% of the patients, respectively. In a dose-ranging, double-masked, multicenter, phase 2 trial including subjects with CRVO for 6 months or less duration randomly assigned to receive pegaptanib sodium (0.3 and 1 mg) or sham injections every 6 weeks for 24 weeks. Results at week 30, 36% subjects treated with 0.3 mg of pegaptanib sodium and 39% treated with 1 mg gained 15 or more letters from baseline versus 28% sham-treated subjects [26]. The main problem of these drugs arises from the deal of what will happen when injections get stopped. In a recent review from the Cochrane database, the authors conclude that ranibizumab and pegaptanib sodium have shown promise in the short-term treatment of nonischemic CRVO macular edema. However, effectiveness and safety data from larger randomized clinical trials with follow up beyond six months are not yet available. There are no randomized clinical trials data on anti-VEGF agents in ischemic CRVO macular edema. The use of anti-VEGF agents to treat this condition therefore remains experimental [27].

Vitrectomy

Pars plana vitrectomy (PPV) techniques are used to address complications of CVO and, in investigational studies, to attempt to alter the natural course of the disease. Eyes with nonclearing vitreous hemorrhage from secondary r...