Ординатура / Офтальмология / Английские материалы / Textbook of Vitreoretinal Diseases and Surgery_Natarajan, Hussain_2008

Textbook of Vitreoretinal Diseases and Surgery

Introduction

Vitreous hemorrhage is defined as the presence of extravasated blood within the vitreous cavity. The vitreous cavity is outlined by the zonular fibers and posterior lens capsule anteriorly, the nonpigmented epithelium of the ciliary body laterally, and the internal limiting membrane of the retina posteriorly and posterolaterally. Vitreous hemorrhage can present with sudden visual loss, the development of vitreous floaters or sometimes no symptoms at all, depending on severity and localization. This condition can have many etiologies, the nature of which will determine the precise treatment required.

Etiology

Various etiologies cause vitreous hemorrhage (Table 10-1). The blood originates mostly from retinochoroidal pathology. Vitreous hemorrhage can develop in three ways, firstly from abnormal retinal vessels (i.e. neovascularization); secondly, from avulsed retinal vessels or breaks; and thirdly, by breaking through the retina from the subretinal space. For the first two processes, most vitreous hemorrhage occurs during posterior vitreous detachment.

Neovascularization of the retina is common to some of the etiologies such as diabetes, retinal vein occlusion and sickle-cell anemia, and usually results from retinal ischemia. Angiogenic factors, such as vascular endothelial growth factor (VEGF), have been suggested to be the most important biological cytokines for retinal neovascularization.1-5 It has been reported that between 6% and 54% of vitreous hemorrhage resulted from proliferative diabetic retinopathy.6,7

Vitreous Hemorrhage: Recent and Future Management

Vitreous hemorrhage combined with avulsed retinal vessels and/or breaks has a high risk of retinal detachment because blood itself is a risk factor for proliferative vitreoretinopathy.8,9 Determination of the cause of the hemorrhage is crucial for visual recovery and timely management. Vitreous hemorrhage from retinal avulsion should be considered more likely if the patient has a history that includes:

1.A previous history of retinal break or detachment;

2.Myopia;

3.A previous history of trauma;

4.No systemic history of diabetes, hypertension or sickle cell anemia.

Age, sex and race ethnicity should also be considered whilst defining the cause of vitreous

hemorrhage. For example, age-related macular degeneration is rarely seen below the age of 40. Sickle cell anemia-related proliferative retinopathy should be considered among black patients. Similarly, trauma is a common cause of vitreous hemorrhage among young patients. The natural history and prognosis depend on the underlying etiology of the vitreous hemorrhage.

Evaluation and Differential Diagnosis

Textbook of Vitreoretinal Diseases and Surgery

A

B

FIGURES 10-1A and B: B-scan is an useful tool to diagnose and evaluate the VH. A. B-scan from a victim of PDR with VH before surgery showed vitreous opacification. B. B-scan from the same patient after surgery showed clear vitreous

Grading of Vitreous Hemorrhage

There is no single accepted standardized scale for grading vitreous hemorrhage. The scale depends on the entity and purpose of each specific study. Most studies grade the vitreous hemorrhage in a qualitative (mild/moderate/severe) or quasi-quantitative (1+ to 4+) approach.8,9,11,12 Vitreous hemorrhage is usually graded on the basis of the fundus, as visualized by ophthalmoscopy. Bhavsar et al13 developed a grading scale by dividing the fundus into twelve divisions like a clock

110 face and designating a score between 0-4 for each division. The twelve scores are summed to give a

Vitreous Hemorrhage: Recent and Future Management

FIGURE 10-2: B-scan showed suspected tractional retinal detachment (upper) and A-scan confirmed the tractional retinal detachment, which has high reflectivity (bottom)

total hemorrhage point score. Some patients, for instance after ocular trauma, may present with corneal opacity, hyphema, dense cataract or other anterior segment pathologies which can interfere with this grading procedure. In these cases, ultrasonography may provide an alternative approach.

Generally, vitreous hemorrhage can be graded as either localized or diffuse by its extent. It can also be graded according to the visibility of the fundus. Table 10-2 shows the grading system used

Vitreous Hemorrhage: Recent and Future Management

is necessary and beneficial. New strategies for the treatment of vitreous hemorrhage, such as pharmacologic vitreous liquefaction, may become important in the future.

CURRENT TREATMENTS

Observation

Restricting patient activity and elevating the head of the patient’s bed are conservative measures that are usually initially recommended. Patching and bed rest might help the blood to settle sufficiently to allow the superior peripheral retina to be examined for scleral depression within 24 hours.14,15 Ultrasonography could be performed regularly to see if there is development or concomitant presence of retinal detachment. Urgent vitrectomy is needed if retinal detachment has developed in combination with vitreous hemorrhage. For those patients where the blood is not surgically removed, a careful and frequent follow-up using serial B-scan ultrasound improves the reliability of the diagnosis at each visit, until such time as the vitreous hemorrhage resolves itself sufficiently to allow a full and proper examination of the retina. A confirmed retinal tear, retinal detachment or other fundus pathology are most appropriately treated by laser treatment or by vitrectomy. In children, observation (50.0%) was the most common treatment modality for those with vitreous hemorrhage.16

Pan-retinal Photocoagulation (PRP)

Whenever the fundus is adequately visualized, Pan-Retinal Photocoagulation (PRP) is always performed to stabilize the vitreous, or to achieve neovastularization regression, despite vitreous hemorrhage in diabetic retinopathy or in other retinal ischemic diseases with retinal neovascularization.17 This procedure may hasten the resorption of vitreous hemorrhage and reduce complications in the vitrectomy surgery subsequently performed.

Cryotherapy

Retinal cryotherapy against vitreous hemorrhage secondary to diabetic retinopathy and other etiologies has been reported with varying success. Benedett et al. reported 238 eyes with vitreous hemorrhage secondary to diabetic retinopathy when followed up after 6 months. Fifty percent of these eyes had reduced vitreous hemorrhage, 33% had no change, and 17% had increased vitreous hemorrhage.24 Postoperative retinal detachment occurred in 4% of eyes. Seventeen percent of eyes had recurrent vitreous hemorrhage and 15% eventually underwent vitrectomy. Visual acuity 6 months post cryotherapy had improved in 44%, was unchanged in 23% and had decreased in 33% of eyes. Cryotherapy treatment did not improve the visual outcome in comparison with vitrectomy and might have increased the breakdown of the blood retinal barrier and worsened ocular inflammation.25 With the wide availability of vitrectomy machines nowadays, cryotherapy is only rarely used.

Pars Plana Vitrectomy

Pars plana vitrectomy is the standard treatment for nonclearing vitreous hemorrhage. Diabetic vitreous hemorrhage remains a major indication for pars plana vitrectomy despite the worldwide use of PRP. Clinical information for the treatment of diabetic vitreous hemorrhage has mostly been derived from a single randomized clinical trial known as the Diabetic Retinopathy Vitrectomy Study (DRVS).11,26-28 This study evaluated the timing of vitrectomy for vitreous hemorrhage. The DRVS enrolled and managed patients between 1976 and 1980, during the early days of vitrectomy surgery.

The first report was published in 1985.28 The study demonstrated that in type 1 diabetic patients 113

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with vitreous hemorrhage, vitrectomy performed within 6 months gave a more favorable outcome than if surgery was referred for 1 year or longer. For the type 2 patients however, the results at these two different intervals were essentially the same. It is noteworthy that the DRVS recruited patients before the endolaser had been widely used. Pars plana vitrectomy outcomes improved with the introduction of the endolaser and modern instrumentation.33-37 Therefore, the indications of surgery were not limited by the results from DRVS.

The use of long-acting gas after diabetic vitrectomy has been found to reduce recurrent postoperative vitreous hemorrhage.38 Recently, using smaller gauge cutters (23 or 25 gauge) during vitrectomy has been found to shorten total surgical time, reduce surgical trauma, and fasten wound healing.39-42 Injecting an anti-VEGF antibody, bevacizumab (Genentech, San Francisco, CA), resulted in rapid regression of retinal neovastularization and fast resolution of vitreous hemorrhage in some eyes that had diabetic retinopathy.43 Pre-vitrectomy application of bevacizumab (Genentech, San Francisco, CA) has also induced fibrovascular tissues to regress, thereby reducing the likelihood of bleeding during surgery or of recurrent vitreous hemorrhage post-surgery.44,45 Although these antiVEGF agents appeared to be well tolerated within diabetic eyes, it is noteworthy that these agents are still off-label for this particular application. The potential benefits and complications of these anti-VEGF agents need to be verified by more studies. Nowadays, vitrectomy for severe diabetic vitreous hemorrhage is performed within 3 months for type 1 diabetics and within 6 months for type 2 diabetics. Even more rapid vitrectomies have been advocated recently. Surgical goals include removal of vitreous hemorrhage to provide a clear medium, excision of the posterior hyaloid and epiretinal membrane to relieve vitreoretinal traction, and applying endolaser photocoagulation to achieve regression of proliferative tissue.

Post-vitrectomy, patients with nondiabetic vitreous hemorrhage have a better visual prognosis than patients with diabetic vitreous hemorrhage. Vision improved in 80% of cases with vitreous hemorrhage secondary to retinal or choroidal vascular disease.47 Vision improved in 98% of patients with non-vascular etiologies.46 The prognosis of patients after vitrectomy for vitreous hemorrhage secondary to retinal venous occlusive disease depends on the type of the occlusion. Patients with branch retinal vein occlusion were reported to experience improved visual acuity in 88-100% of cases after vitrectomy.47-49 The prognosis is worse in patients with central retinal vein occlusion with improvement of visual acuity occurring in one third of these cases.47,49 The visual prognosis does not depend on the vitreous hemorrhage and its clearing, but more on the damage to the retina done by the vein occlusion. Vitrectomy for vitreous hemorrhage secondary to sickle cell anemia is rarely necessary and is associated with many complications.50

Vitrectomy for vitreous hemorrhage resulting from Terson’s syndrome has a very good prognosis, with improved visual acuity in most patients.46 Vitrectomy for nonclearing vitreous hemorrhage has been successfully performed in many other underlying conditions, such as retinal tear,46,48 avulsed retinal vessels,46,48 leukemia and anticoagulant therapy,48 Eale’s disease,48 Behcet’s diseas,48,51 uveitis,47,48 and surgical trauma.46,48

Most surgeons will agree that immediate vitrectomy is indicated for vitreous hemorrhage with IOFB, but timing the vitrectomy for vitreous hemorrhage in the management of open globe injury remains a controversial issue. Proponents of performing vitrectomy between 4 and 14 days after injury argue that the uveal congestion which develops after trauma may increase the risk of uncontrollable hemorrhage; furthermore, a lack of separation of the posterior vitreous makes complete

114 removal difficult. Experimental evidence points toward heightened fibrous proliferation when surgery is delayed by 2 weeks, which can inflict further retinal damage and make the operation

Vitreous Hemorrhage: Recent and Future Management

more difficult.55 However, some authors have argued that vitrectomies performed 14 days after penetrating ocular injury are associated with improved visual outcomes.56,57

FUTURE TREATMENTS

Hyaluronidase (Vitrase)

Hyaluronidase hydrolyzes hyaluronic acid by splitting the glucosaminidic bond between C1 of the glucosamine moiety and C4 of glucoronic acid, thereby causing the breakdown of organized proteoglycan structures and liquefaction of the vitreous. Purified ovine hyaluronidase, Vitrase (ISTA Pharmaceuticals, Irvine, CA), induces breakdown of the vitreous structure by acting on hyaluronan and chondroitin sulfate. Purified ovine hyaluronidase has been studied in the “Vitrase for Vitreous Hemorrhage Study” consisting of two clinical trials. These Phase III clinical trials randomized patients to a single intravitreal injection of a 7.5 IU, 55 IU, or 75 IU dose of Vitrase versus saline injection.58,59 These studies enrolled 1,306 patients with a BCVA worse than 20/200 and with severe vitreous hemorrhage due to almost any etiology that obscured visualization of the fundus and was present for at least 1 month. The primary efficacy endpoint was the clearance of the vitreous hemorrhage sufficient for laser photocoagulation complete to at least 6 pm (on the retina clock), with photographic documentation of hemorrhage clearance. Evidence that treatment was not necessary after 3 months was not found. However, the secondary endpoints including reduction in vitreous hemorrhage density, improvement in BCVA, and clinical assessment of therapeutic utility (hemorrhage clearance sufficient to allow treatment to begin or for the decision that treatment was not necessary) were met and were statistically significant and in favor of Vitrase. For primary efficacy, statistical significance was reached in the 55 IU dose group by months 1 and 2. At the 55 IU dose, 13.2%, 25.5%, and 32.9% of patients reached primary efficacy by months 1, 2 and 3 versus 5.5%, 16.2%, and 25.6% of salinetreated patients. In addition, all of the endpoints (both primary and secondary) were met for the subset of patients with vitreous hemorrhage due to diabetic retinopathy who were treated with the 55 IU dose of Vitrase (unpublished). The major adverse events in the entire study population included typically self-limited iritis which occurred in 59% (55 IU) and 62% (75 IU) of treatment eyes versus 33% of saline control eyes. Hypopyon occurred in 2% (55 IU) and 5% (75 IU) of treatment eyes versus 0.0% of the saline control eyes. The rate of retinal detachment was similar between the groups and in most cases was due to tractional detachments.

Plasmin

Plasmin enzyme is a nonspecific protease that acts on laminin, fibronectin, and fibrin and may act on the matrix between collagen fibrils.60 The vitreoretinal junction is mainly composed of laminin and fibronectin,60 and therefore plasmin could act on the vitreoretinal junction. Plasmin has been used in humans to cleave the vitreoretinal junction and allow less traumatic detachment of the posterior hyaloid from underlying retina.61-64 Plasmin enzyme also produces vitreous liquefaction which may contribute to faster blood resorption;65 this may be beneficial in managing patients with vitreous hemorrhage. Previous clinical studies with plasmin have shown an excellent safety profile when applied to human eyes. No major complications were found when plasmin was used in these trials.61-64 Plasmin (Bausch & Lomb, Inc.) and microplasmin (ThromboGenics) have been developed and are either approved or currently undergoing phase II clinical trials for treatment of vitreomacular traction.

Vitreous hemorrhage is a manifestation of varying etiology that often has systemic associations.

A detailed ocular and systemic history, thorough clinical and laboratory evaluation and meticulous 115

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and often repeated ocular ultrasonography can help to make an etiological diagnosis. Prompt and judicious laser photocoagulation (where indicated) can prevent visual loss in the majority of eyes. Early surgery (in eyes with retinal detachment) can salvage many of these eyes from going irreversibly blind. In other cases, where laser treatment is not possible or does not cause adequate resolution of the pathology, vitreous surgery can be performed as an elective procedure. With careful attention to the principles of vitreous surgery and regard for the underlying pathology, surgery can successfully rehabilitate sight in patients who have suffered from vitreous hemorrhage.

References

Vitreous Hemorrhage: Recent and Future Management

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24.Benedett R, Olk RJ, Arribas NP, Okun E, Johnston GP, Boniuk I, Escoffery RF, Grand MG, Schoch LH. Transconjunctival anterior retinal cryotherapy for proliferative diabetic retinopathy. Ophthalmology 1987;94: 612-9.

25.Veckeneer M, Van Overdam K, Bouwens D, Feron E, Mertens D, Peperkamp E, Ringens P, Mulder P, Van Meurs

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43.Arevalo JF, Wu L, Sanchez JG, Maia M, Saravia MJ, Fernandez CF, Evans T. Intravitreal bevacizumab (avastin) for proliferative diabetic retinopathy: 6-months follow-up. Eye 2007.

44.Ishikawa K, Honda S, Tsukahara Y, Negi A. Preferable use of intravitreal bevacizumab as a pretreatment of vitrectomy for severe proliferative diabetic retinopathy. Eye 2007.

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46.Isernhagen RD, Smiddy WE, Michels RG, Glaser BM, de Bustros S. Vitrectomy for nondiabetic vitreous hemorrhage. Not associated with vascular disease. Retina 1988;8:81-7.

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