32 Vitreous

349 FAMILIAL EXUDATIVE VITREORETINOPATHY 743.51

(Criswick–Schepens Syndrome)

Alexander P. Hunyor, MBBS, FRANZCO, FRACS

Sydney, Australia

Joseph E. Robertson, Jr., MD

Portland, Oregon

Familial exudative vitreoretinopathy (FEVR) is a hereditary abnormality characterized by abnormal vascularization of the peripheral retina, which may appear strikingly similar to retinopathy of prematurity (ROP). Ocular involvement is bilateral and often symmetric. The condition was first described in 1969 by Criswick and Schepens. Also formerly known as autosomal dominant exudative vitreoretinopathy, this condition has now been described in X-linked recessive and autosomal recessive forms. It is an important cause of retinal detachment in younger patients, especially in the Japanese population.

ETIOLOGY

●Autosomal dominant inheritance.

●Most common (and classically described) form.

●High penetrance and highly variable expressivity.

●3 loci identified:

●EVR1 — chromosome 11q, FZD4 gene mutation

●EVR3 — chromosome 11p

●EVR4 — chromosome 11q, LRP5 gene mutation.

●X-linked recessive inheritance.

●Locus: EVR2 — chromosome Xp11.4.

●More severe form, due to mutation of the Norrie disease gene, NDP.

●Autosomal recessive inheritance.

●One recessive EVR4 mutation in LRP5 has been described.

COURSE/PROGNOSIS

Findings generally remain stable once adulthood is reached. Disease progression with visual loss is uncommon after age 20, although patients are at risk of late rhegmatogenous retinal detachment.

DIAGNOSIS

Classification

Various classification schemes have been proposed to describe the clinical course and angiographic findings in FEVR. Most recently, a staging scheme similar to that for ROP has been suggested by Pendergast and Trese.

Clinical signs and symptoms

Symptomatic patients usually present in childhood with strabismus or reduced visual acuity due to retinal fold or detachment. Clinical appearance may simulate that in ROP, but there is rarely a history of low birth weight. Patients with milder forms of FEVR are commonly asymptomatic and have good visual acuity. Findings include peripheral avascular zones that are usually temporal and wedge-shaped but may be more extensive; vasodilatation and arteriovenous anastomosis; abnormal vitreoretinal adhesion; and a V-shaped area of chorioretinal degeneration corresponding to the avascular zone. The peripheral avascular zone usually persists without regression or neovascular complications, in contradistinction to ROP, in which the peripheral retina vascularizes as the disease regresses.

In more advanced cases, patients may develop retinal neovascularization, intraretinal and subretinal hemorrhage and exudate, and fibrovascular membranes that can lead to cicatricial complications similar to those of ROP. These include retinal (falciform) folds; tractional, rhegmatogenous, or combined retinal detachments; and macular ectopia. Patients may present with advanced retinal detachment complicated by neovascular glaucoma, band keratopathy, or even phthisis bulbi.

Other findings may include:

●Myopia;

●White-with-pressure and white-without-pressure, cystoid degeneration, and retinoschisis;

●Cystoid macular edema, epiretinal membrane;

●Vitreous hemorrhage is relatively uncommon;

●Isolated intraretinal deposits may be the only clinical manifestation.

Diagnosis is based on the spectrum of clinical features listed previously, in combination with:

●History of familial tendency;

●No history of prematurity, low birth weight, or supplemental oxygen therapy.

Detailed family history and examination of relatives, who are often asymptomatic, is essential for correct diagnosis and proper genetic counseling.

Vitreous • 32 SECTION

In most instances, a specific cause has not been identified, although bilateral cases may occasionally be associated with trisomy 13, X-linked recessive mutations, and autosomal recessive mutations.

The incidence of the disorder has not been established.

COURSE/PROGNOSIS

The child’s lens is usually clear initially. With time, disruption of the lens capsule and fibrovascular ingrowth occurs, with progressive lenticular opacification and swelling and a secondary shallowing of the anterior chamber. Typically, glaucoma develops in advanced cases; it may result from either openor closed-angle mechanisms. Several factors contribute to closure of the anterior chamber angle, including peripheral anterior synechiae, anterior displacement of the iris-lens diaphragm, lens swelling, and seclusion of the pupil. Open-angle glaucoma has been attributed to chronic uveitis and intraocular hemorrhage. Spontaneous hemorrhage into the vitreous, lens, and anterior or posterior chamber may originate from either abnormal iris vessels or the retrolental tissue. These processes may result in a blind, painful eye if surgical intervention does not take place.

Early surgical treatment has been recommended to prevent the progressive changes that result in blindness, phthisis, and globe loss. It has been recommended that the treatment for this condition be determined by (1) evidence of visual function, (2) clinical progression, and (3) the absence of severe optic nerve or retinal involvement, intractable amblyopia, or phthisis.

DIAGNOSIS

PHPV can be divided into anterior, intermediate, and posterior anatomic types on the basis of findings on clinical examination supplemented with ancillary studies. Visual function is evaluated with pupillary responsiveness, visual evoked response, and electroretinography, whereas the posterior segment can be assessed with ophthalmoscopy, ultrasonography, computed tomography, and magnetic resonance imaging.

Anterior PHPV occurs with incomplete reabsorption of the tunica vasculosa lentis (17%). Clinically, it is associated with:

●Engorged radial iris vessels;

●Microcornea (diameter <10 mm);

●Various degrees of persistence of the tunica vasculosa;

●Mittendorf dot to dense retrolental vascularized membrane;

●Elongated ciliary processes;

●Shallowing of the anterior chamber;

●Microphthalmos;

●Progressive cataract.

Posterior PHPV results from incomplete regression of the primary vitreous, particularly the hyaloid vessel remnants (25%). It is associated with:

●Complex vitreous membranes with secondary retinal changes.

Small whitish membranes overlying the optic nervehead (Bergmeister’s papillae) to large peripapillary and posterior pole membranes with secondary membranes.

●Traction retinal detachment.

Intermediate PHPV combines features of both anterior and posterior PHPV (58%) (Figure 350.1).

FIGURE 350.1. Persistent hyperplastic primary vitreous.

Differential diagnosis

●Leukocoria in children.

●Retinoblastoma.

●Congenital cataract.

●Retrolental fibroplasia.

●Parasitic endophthalmitis.

●Norrie’s disease.

●Incontinentia pigmenti.

TREATMENT

Medical

●Good visual results in children with visually significant monocular structural abnormalities have been reported; the treatment issues are similar to those with monocular congenital cataracts. Effective surgical treatment and treatment for amblyopia must be instituted for both groups during the critical period for maturation of the central nervous system; the best results occur when treatment is initiated within the first 2 months of life.

●Early surgery must be complemented by early optical correction and occlusion therapy, usually within 2 weeks of surgery. Both extended-wear (Silisoft) and gas-permeable hard contact lenses have been used. Frequent lens changes are required because of the eyes’ dynamic growth. Intraocular lens implantation has been reported as potentially beneficial for the management of patients with unilateral involvement.

●Amblyopia therapy is initiated in conjunction with the optical correction. Several part-time patching regimens have been developed. The visual development is monitored with the binocular fixation pattern response, and frequent postoperative visits are required.

Surgical

A posterior transciliary approach is used to access the peripheral lens remnants, vitreous base, and posterior vitreous cavity, facilitating membrane dissection in eyes with extensive proliferation. In situations in which the retina is drawn anteriorly over the pars plicata or into a retrolental mass, the translimbal

Vitreous Primary350 CHAPTERHyperplastic Persistent •

Vitreous • 32 SECTION

other types of retinal damage. Loss of contact inhibition causes the surrounding glial or retinal pigment epithelial cells to migrate to both surfaces of the retina and proliferate. These cells then migrate farther and cover the posterior surface of the detached posterior hyaloid face. Fibronectin-lined, coated pits serve as attachments of retinal pigment epithelial or glial cells to collagen fibers and other components of the extracellular matrix. The migration/contraction mechanism causes tangential force on the retina, resulting in multiple starfolds and fixed folds. Similarly, the vitreous collagen matrix contracts because of a similar hypocellular process.

DIAGNOSIS

Clinical signs and symptoms

Ocular or periocular

●Retina: epiretinal membranes, fixed folds, starfolds, subretinal placoid or dendritic proliferation.

●Vitreous: condensation, contraction, pigmentation, and posterior vitreous detachment.

●Other: visual loss.

TREATMENT

Surgical

●The surgical objective is to enable the retina to conform to the retinal pigment epithelium. In cases of moderate starfolds without static vitreous traction, scleral buckling without vitreous surgery is indicated. Minimal retinopexy to the breaks should be used to avoid inflammation and further proliferation. Re-treatment of the retinal pigment epithelium and multiple rows of retinopexy should be avoided to reduce recurrent PVR and inflammation. Post-reattachment retinopexy helps to reduce retinal pigment epithelium and glial cell proliferation as well as inflammation and increased vascular permeability but it requires a vitrectomy approach. Laser endophotocoagulation causes less PVR than does cryotherapy but it can only be used with vitrectomy.

●A broad, moderately high, 360-degree encircling buckle with a smooth contour should be used. This is best achieved with a silicone explant and two or three mattress sutures per quadrant. The posterior scleral bites should be single, long, and circumferential and as posterior as possible to avoid damage to the vortex veins. The anterior bites should be limbus-parallel and placed in the scleral condensations at the muscle ring representing the external landmark of the ora. Sutures of 5-0 monofilament nylon are preferred to Mersilene sutures because the former can be tied without the help of an assistant and do not slip. The ends must be cut on the knot to avoid protrusion through the conjunctiva. The broad buckle extends back to the thicker, stronger, untreated retina and to the ora to prevent anterior leakage. Complete or near-complete drainage of subretinal fluid (SRF), preferably using a direct needle drainage method, is required to achieve reattachment and create space for the large buckle. Vitrectomy in aphakic eyes or anterior chamber paracentesis in phakic or pseudophakic eyes may be necessary to achieve volume requirements. Air or, preferably, expandable C3F8 gas injection ‘seals’ the retinal breaks via surface tension and allows restoration of a trans-retinal pressure gradient and more complete drainage of SRF. Because air (or gas) causes attachment of the anterior retina

and posterior displacement of SRF, transscleral drainage of SRF should be performed very posteriorly if done after air (or gas) injection to avoid retinal incarceration in the drainage site.

●Vitreous surgery should be performed when it is anticipated that scleral buckling alone cannot compensate for vitreous traction and periretinal membrane contraction sufficiently to reattach the retina. In most instances, the lens should be removed with trans-pars plana lensectomy or preferably with intraocular lens implantation. Phaco to permit better release of the anterior traction and for decompartmentalization, which may reduce recurrent proliferative vitreoretinopathy. Endocapsular lensectomy with the aspirating phacofragmenter and linear (proportional) suction should be used if there is any substantial inflammation or any reason to avoid phaco. The anterior and posterior portions of the vitreous cortex are usually in contact, resulting in a frontal plane configuration. This frontal plane component should be removed first, preferably with the vitreous cutter and minimal, linear suction. The anterior PVR radial traction then should be resected with the vitreous cutter, if sufficient distance exists between the anterior attachment at the pars plana and the posterior attachment of this former peripheral cortical vitreous to the retina at the equator. A 25-, 23-, or 20-gauge delamination scissors are required in many instances to resect this anterior loop.

●The epiretinal membrane can be peeled away from the retina when it is minimally adherent. End-opening, 25G DSP forceps or conformal forceps are used for inside-out peeling of epiretinal membranes; picks, needles and forceps with one blade under the epiretinal membrane cause more trauma to the retina. In cases of stronger adherence, it is better to perform segmentation or delamination using fine curved scissors with blades essentially parallel to the retina. Segmentation of the epiretinal membrane in the center of a starfold and between each fold releases the tangential traction. If the membrane is dense and well developed, it can be delaminated from the retinal surface using both scissor blades between the retina and membrane. The goal is to release sufficient tangential traction to allow retinal conformation to the retinal pigment epithelium with minimal damage to the retina, not removing all membranes.

●Subretinal membranes can be segmented or removed with forceps if they are creating sufficient contour change in the retina to prevent reattachment. This can be accomplished through a pre-existing retinal break, or a retinotomy can be created for this purpose, using the closed forceps to push through the retina. Large retinotomies are not required for subretinal surgery and they do unnecessary damage to the retina.

●Internal drainage of SRF should precede fluid-air exchange to enable removal of all posterior SRF through preexisting peripheral retinal breaks. Drainage retinotomies are used if the peripheral breaks can be easily accessed for internal drainage. Use of internal drainage often reduces the need for perfluoroctane except in cases of giant breaks without PVR. Internal drainage of SRF through a tapered, angulated cannula placed through a convenient retinal break and held near the retinal pigment epithelium allows a feasibility test for intraoperative retinal attachment. The appearance of subretinal air indicates the failure to release all tangential forces on the retina and the need for further forceps membrane peeling, segmentation, delamination, retinectomy, or scleral buckling. It may also indicate inoperability.

Vitreoretinopathy351 CHAPTER Proliferative •

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If internal drainage of SRF and fluid-air exchange with continued internal drainage of SRF results in subretinal air, incremental retinectomy with the vitreous cutter can be effective to release tangential forces on the retina. Retinectomy is also indicated when the retina is incarcerated in a wound or previous drain site and when dense membranes are strongly adherent over broad areas of atrophic retina. Air-gas exchange or air-silicone exchange should be performed after internal drainage of SRF, fluid-air exchange, and laser endophotocoagulation. Confluent, moderate-intensity endolaser should be used around breaks. Laser retinopexy in rows and panretinal laser photocoagulation (PRP) should be avoided to reduce tissue damage. Laser indirect ophthalmoscopy is not necessary in vitreous surgery and may cause corneal and iris damage as well as light- scatter-mediated macular damage.

●Air (gas) surface tension management should be used in all cases requiring vitrectomy because the viscosity of the vitreous is significantly reduced, preventing the retinal pigment epithelial pump from maintaining a transretinal pressure gradient. Subsequent air-gas exchange allows creation of a total fill of the vitreous space without hypotony or multiple small bubbles. Using an 18% concentration of C3F8 has been shown to produce better outcomes than 25% SF6 because the bubble lasts longer than 3 weeks instead of 1 week. Concentrations greater than these are not used because expansion would cause elevation of intraocular pressure with a total fill. The gas is injected through the infusion cannula, preferably using a power gas injector. Fluid egress is accomplished through an extrusion cannula positioned through the retinal break, near the retinal pigment epithelium, and is controlled by a foot-operated linear suction system.

Surface tension management with highly purified silicone oil (1000 centistokes) is preferable to the use of gas for most advanced or recurrent cases of PVR. If a posterior chamber lens is in place, it will maintain the silicone posteriorly, preventing corneal contact and subacute angle-closure glaucoma. If the eye is phakic, endocapsular lensectomy or phaco should be utilized, as cataract formation universally follows extended periods of silicone oil usage. An Ando inferior iridectomy should be used in all aphakic eyes to prevent silicone pupillary block. The capsule should be removed with diamond-coated forceps to prevent fibrosis at the iridectomy site and the development of cyclitic membranes and hypotony. Viscoelastics, blood, and inflammation increase emulsification of the silicone oil and should be avoided, if possible. Aphakic patients who have received silicone treatment are instructed to avoid prolonged supine positioning to reduce the incidence of subacute angleclosure glaucoma and corneal contact. The author removes silicone oil in about 10% of cases and is opposed to performing multiple procedures just to enable silicone removal, especially in older and pseudophakic patients. Silicone is used for rhegmatogenous confinement and facilitates stabilization of inferior and peripheral retinal detachments. Silicone should be removed only if all breaks are sealed by retinopexy.

●Scleral buckling using a 9-mm-wide, 360-degree silicone explant imbricated flush with the surface of the globe and sutured end-to-end is used in most cases. It is a mistake to think of PVR as a localized disease and to buckle only the abnormal-appearing areas. An encircling band is required. Care should be taken to avoid muscle removal or damage to the vortex veins, especially during buckle revision.

PRECAUTIONS

●Vitreous (periretinal membrane) surgery should be done when it is apparent that conventional scleral buckling alone will not be effective and the eye has minimal inflammation and ‘mature’ epiretinal membranes.

●Inside-out forceps membrane peeling with diamond-coated or conformal forceps is superior to other membrane peeling methods.

●Laser retinopexy should not used only around retinal breaks, not in PRP fashion.

●Subconjunctival steroids decrease the release of fibrin and reduce proliferation and therefore should be used in all cases without steroid glaucoma. Systemic steroids should never be used in these cases because of systemic side effects.

COMMENTS

The above techniques have approximately a 95% intraoperative anatomic success rate, with 75% long-term anatomic success and a 50% long-term visual success rate. Visual acuities are better than 5/200 in the author’s series. With the possibility of bilateral visual loss in PVR, it is mandatory to consider this procedure with its greater success rate and 0.5- to 1.5-hour operating time to retain an eye with ambulatory vision.

Antiproliferative drugs, radiation therapy, and intraocular steroids have not been proven effective against PVR.

REFERENCES

Abrams GW, Ryan SJ, Lai MY, et al: Vitrectomy with silicone oil or longacting gas in eyes with severe proliferative vitreoretinopathy: results of additional and long-term follow-up. Silicone Study Report 11. Arch Ophthalmol 115:335–344, 1997.

Campochiaro PA: Pathogenic mechanism in proliferative vitreoretinopathy. Arch Ophthalmol 115:237–241, 1997.

Charteris DG: Proliferative vitreoretinopathy: pathobiology, surgical management, and adjunctive treatment. Br J Ophthalmol 79:953–960, 1995.

van Horn DL, Aaberg TM, Machemer R, et al: Glial cell proliferation in human retinal detachment with massive periretinal proliferation. Am J Ophthalmol 84:383–393, 1977.

352 VITREOUS HEMORRHAGE 379.23

Irvin L. Handelman, MD

Portland, Oregon

Vitreous hemorrhage is a common cause of profound visual loss. Understanding the pathogenesis and etiology is important in its successful management. Current therapy has two components: prophylaxis and vitreous surgery.

ETIOLOGY/INCIDENCE

Blood enters the vitreous from ruptured vessels derived from the retina or uveal tract. From the retinal circulation there are both proliferative and nonproliferative retinopathies. Traction

352 CHAPTERHemorrhage Vitreous •

Vitreous • 32 SECTION

multiple mobile, dot-like floaters. The presence of photopsia often points to a tractional etiology such as a retinal tear or detachment. In addition, sectoral visual field loss may indicate a retinal detachment or branch retinal vein occlusion. In all but rare cases of proliferative diabetic retinopathy, the diagnosis of diabetes mellitus has been well documented. In some cases, such as sickle cell disease and retinal vasculitis, pertinent laboratory findings may help to establish the diagnosis. Consumption of aspirin for its platelet-inhibition properties probably carries little increased risk for vitreous hemorrhage, and this has been established in the Early Treatment of Diabetic Retinopathy study. The risk of other platelet inhibitors and anticoagulants in causing vitreous hemorrhage is controversial.

B-scan ultrasonography can be an invaluable aid in evaluating dense vitreous hemorrhages. This test can document the presence and location of a retinal detachment and sometimes a retinal tear. In the proliferative retinopathies, ultrasound examination can localize and quantify traction on the retina. Visualization of a posterior vitreous detachment is helpful, for example, in following patients with a vitreous hemorrhage since it usually carries a good prognosis unless there is a coexistent retinal tear.

In some individuals sequential ultrasound examinations may be needed to monitor a nonclearing vitreous hemorrhage.

Bedrest with elevation of the head has been advocated to aid in settling and clearing of vitreous hemorrhage. This technique is of uncertain value since normal eye movements tend to disperse blood throughout the eye. However, in some cases settling of the vitreous hemorrhage may allow visualization of a superior retinal break and allow its treatment; similarly increased visualization of the superior retina may facilitate panretinal photocoagulation in cases of proliferative diabetic retinopathy.

PROPHYLAXIS

Treatment of the underlying pathology often will prevent visually significant vitreous hemorrhages.

In most eyes with neovascularization of the optic disc or retina, there is significant underlying ischemia, and most of these eyes will benefit from scatter or panretinal laser photocoagulation. Depending upon the etiology, this is applied to the retinal midperiphery and periphery in all quadrants; however, in cases of segmental pathology, this treatment is restricted to the appropriate area of the retina.

In proliferative diabetic retinopathy the presence of even a small vitreous hemorrhage is associated with a high risk of severe visual loss, and panretinal photocoagulation is indicated to decrease this risk. The value of this technique was definitively demonstrated in the Diabetic Retinopathy study. Generally laser treatment is applied with a green wavelength either at the slit lamp using a contact lens or with the indirect ophthalmoscope; however, other wavelengths, especially red and infrared, also are effective. In general 1200 to 2000 burns are scattered over one to four sessions. Usually only topical anesthesia is required; however, in some cases retrobulbar anesthesia will facilitate complete treatment. The endpoint of panretinal photocoagulation is regression of the neovascularization. Although rarely used, panretinal cryoablation probably is also effective.

Ischemic branch retinal vein occlusions can develop neovascularization of the optic disc and retina as a late development. In general scatter photocoagulation applied to the affected quadrant will, in most cases, produce regression of the new

vessels and prevent further bleeding. Other than applying treatment to a more limited area of the retina, the technique is the same as used in proliferative diabetic retinopathy.

In retinopathy of prematurity, threshold disease can lead to vitreous hemorrhages and retinal detachments. Cryotherapy was initially determined to be effective in stimulating regression of neovascularization. More recently a relatively confluent laser photocoagulation technique applied to the retinal periphery has been used and led to successful involution of new vessels in many cases.

A hemorrhage associated with a symptomatic retinal tear can be caused either from a coexistent posterior vitreous detachment or rupture of a bridging retinal vessel. Appropriate laser photocoagulation or cryotherapy applied around the retinal break can minimize the risk of a retinal detachment. The vitreous hemorrhage, if not severe, will usually clear spontaneously.

However, in a few retinal tears there is an avulsed retinal vessel which may bleed into the vitreous following adequate prophylactic treatment; in some of these cases, if the vitreous is sufficiently clear, the avulsed vessel can be directly treated with laser photocoagulation.

Pneumatic retinopexy is a minimally invasive technique which can be used to manage selected retinal detachments that can be associated with vitreous bleeding; in this technique an intravitreal injection of a long-acting gas tamponade, such as sulfur hexafluoride, combined with laser photocoagulation or cryotherapy can seal retinal breaks, repair the detachment, and minimize the risk of additional bleeding. Repair of retinal detachments by scleral buckling techniques can be accomplished in the presence of mild to moderate vitreous hemorrhages with little risk of complications; usually successful repair of the retinal detachment will decrease the risk of recurrent bleeding.

VITREOUS SURGERY

A vitrectomy will be needed for nonclearing, severe vitreous hemorrhages or for eyes in which there are recurrent hemorrhages of moderate severity. In general a three-port pars plana vitrectomy is the usual approach. Depending upon the underlying pathology, there may be special intraoperative techniques to gain a successful outcome. Recently a sutureless vitrectomy technique has been developed using 25-gauge instrumentation, and this can lead to shorter operating times and faster postoperative rehabilitation.

In the case of rhegmatogenous retinal detachments, the presence of extensive hemorrhage requires a vitrectomy. Currently most surgeons would also employ some degree of a scleral buckling technique. However, at the present time there is some movement away from scleral buckling when a vitrectomy is required for management of a retinal detachment with or without vitreous hemorrhage. This surgery is usually combined with laser photocoagulation and intravitreal gas or silicone oil. Contusional or perforating injuries associated with dense vitreous hemorrhages usually should be managed with vitrectomy within one to two weeks because of a high risk of retinal detachment.

In proliferative diabetic retinopathy the timing of vitrectomy depends to some extent upon the age of the patient. In general, severe vitreous hemorrhages in the younger, type I diabetics are operated on within about one month of onset of the bleeding if there is no spontaneous clearing. In type II diabetics there is