30 Retina

328 ACQUIRED RETINOSCHISIS

361.10, 361.12

(Degenerative Retinoschisis, Senile

Retinoschisis)

M. Vaughn Emerson, MD

Portland, Oregon

J. Timothy Stout, MD, PhD

Portland, Oregon

ETIOLOGY/INCIDENCE

Acquired retinoschisis is a degenerative condition in which splitting of the peripheral retina occurs at the level of the outer plexiform layer. This results in the formation of an inner layer (closer to the vitreous) and an outer layer (closer to the retinal pigmented epithelium). The resulting schisis cavity gives the retina a cystic appearance, which in more extensive cases may appear bullous.

The condition occurs in 1% to 4% of the population; it occurs in 7% of patients older than 40 and is most frequent in patients older than 50. This distinguishes it from juvenile retinoschisis, which occurs in a much younger population. Juvenile retinoschisis is characterized by schisis at the level of the nerve fiber layer and an X-linked recessive mode of transmission, and is associated with mutations in the XLRS-1 gene. Acquired retinoschisis is usually bilateral (77–85%) and has a predilection for the inferotemporal peripheral retina (80%). The incidence is equal in men and women.

The pathogenesis is unknown. Circulatory compromise may be a factor because the peripheral retina is in a circulatory ‘watershed’ zone. Chronic vitreous traction, perhaps associated with the chronic motility effects of accommodation on the peripheral retina, may also play a role.

COURSE/PROGNOSIS

●Patients are usually asymptomatic, and the condition is discovered on routine examination of the peripheral retina.

●Schisis extends posterior to the equator in 74% of eyes. Progression of posterior extent (more than two disk diameters) occurs in 3% of eyes.

●Circumferential extension (extension of more than one clock hour) is seen in 6% of eyes.

●A new area of developing retinoschisis is seen in 10% of eyes.

●Two percent of eyes will demonstrate spontaneous disappearance of retinoschisis.

●New retinal breaks occur in 6% of eyes, in either the inner or the outer layer of the retinoschisis.

●Schisis-associated retinal detachment occurs in 6% of eyes when fluid passes through an outer layer break and the outer layer comes into apposition with the inner layer.

●Of eyes with outer-layer breaks, 50% to 60% will develop schisis-associated detachments.

●Symptomatic progressive retinal detachment that extends beyond the limits of the schisis cavity occurs in 0 to 0.05% of eyes.

DIAGNOSIS

Clinical signs and symptoms

●Acquired retinoschisis is generally very slowly progressive; as a result, patients are typically asymptomatic. Rarely, posterior extension or associated retinal detachment may lead to severe visual loss.

●New onset of symptoms (photopsias, floaters, or visual field loss) may occur in conjunction with an unrelated posterior vitreous detachment and are usually not related to the schisis.

●The refraction is hyperopic in 80% of patients.

●The inner layer may be pitted in appearance, and 70% of eyes have tiny, glistening yellow-white dots.

●Degenerative retinoschisis may be associated with peripheral cystoid degeneration and pars plana cysts.

●Peripheral blood vessels may appear sclerotic.

●Inner layer breaks, which are usually tiny and difficult to detect ophthalmoscopically, occur in 2% of eyes.

●Outer layer breaks, which are often much larger and have characteristic rolled edges, are present in 4% to 5% of eyes.

●The presence of innerand outer-layer breaks rarely occurs and may lead to retinal detachment.

Laboratory findings

●An absolute scotoma in the area of the retinoschisis is present on visual field testing (in contrast to a relative scotoma in retinal detachment).

●Ultrasonography (including B-scan and ultrasonic biomicroscopy) demonstrates a minimally mobile, thin membrane in the retinal periphery that cannot be decompressed with scleral depression (in contrast to rhegmatogenous

Retina • 30 SECTION

FIGURE 328.1. B-scan ultrasound of retinoschisis.

retinal detachment, in which the subretinal space can be decompressed). This may be useful in cases in which medial opacity inhibits indirect ophthalmoscopy (Figure 328.1).

●Laser photocoagulation will cause a whitening reaction in the outer layer (in contrast to a retinal detachment in which a reaction to laser photocoagulation will not be apparent).

●Optical coherence tomography (OCT) can be used to help differentiate between schisis and detachment.

Differential diagnosis

●Rhegmatogenous retinal detachment: unilateral, relative scotoma on visual field, no reaction to laser photocoagulation; progressive, elevation may be decompressed with scleral depression.

●Retinal macrocyst: associated with long-standing rhegmatogenous retinal detachment; other signs of chronicity may also be seen, including demarcation lines and retinal atrophy and thinning.

●Exudative retinal detachment: shifting fluid may be seen; signs of inflammation or tumor of the retina or choroid may be apparent.

●Tractional retinal detachment: foci of fibrovascular proliferation causing traction are seen; the retina has a concave appearance; traction can cause a secondary retinoschisis, but this is a different entity.

●Choroidal detachment: the detachment is a solid structure under the retina, associated with hypotony; detachment may be present for 360 degrees and apices may localize to the vortex veins.

●Optic nerve pit: from 30% to 40% of patients with optic nerve pit have macular detachment, which may in fact be a macular schisis cavity.

●Venous occlusive disease: patients with central or branch retinal vein occlusion may develop secondary retinoschisis in the distribution of the affected vein; this will be located in the posterior part of the retina and not the periphery, as is seen in acquired retinoschisis.

●Juvenile retinoschisis: this is associated with young males, an X-linked recessive mode of transmission, and a higher

percentage of vitreous hemorrhage (21%) and retinal detachment (16%).

PROPHYLAXIS

Although prophylaxis has been recommended in the past to prevent the progression of retinoschisis or to prevent the formation of a rhegmatogenous retinal detachment, no modality (diathermy, retinal cryopexy, laser photocoagulation) has been demonstrated to be clinically beneficial and in some cases may have worsened the outcome (resulting in retinal detachment, vitreous hemorrhage, maculopathy and proliferative vitreoretinopathy). As a result, prophylactic treatment of acquired retinoschisis is not advised. Asymptomatic localized nonprogressive schisis detachments and retinoschisis with outer layer breaks are the only known precursors of symptomatic progressive retinal detachments and thus should be monitored every 6 months. Treatment should be administered only if symptomatic retinal detachment is seen.

TREATMENT

The treatment of acquired retinoschisis is limited to patients who develop symptomatic, progressive schisis-associated retinal detachments. Local or systemic nonsurgical treatment is not necessary. Bilateral patching of the eyes may be helpful in decreasing the height of the retinal detachment, making surgical intervention easier.

Surgical

●Configuration of the outer layer breaks will determine the mode of treatment.

●Larger and posterior outer layer breaks are difficult to treat with a standard scleral buckle; buckling is associated with a higher incidence of macular distortion.

●Smaller and peripheral outer layer breaks causing schisisdetachments are treated with a standard scleral buckle, retinal cryopexy, and external subretinal fluid drainage. The external drainage is attempted in the bed of the outer layer break; this may allow the drainage of subretinal fluid and collapse of the schisis cavity. Even if the retinoschisis cavity does not collapse, as long as the outer layer break is supported, the retina should remain attached.

●For schisis detachments with large and posterior outer-layer breaks, pars plana vitrectomy with internal drainage, laser photocoagulation, and gas-fluid exchange is recommended. Pars plana vitrectomy is performed; as much of the posterior hyaloid as can be removed without tearing the inner layer of the schisis cavity is removed. If an inner-layer break overlies a posterior outer-layer break, internal drainage is done through the inner-layer break to drain subretinal and schisis cavity fluid. If an inner-layer break is not present, endodiathermy is used to make an opening in the inner layer over a posterior outer-layer break. Once the retina is flattened, endolaser is used to surround the outerlayer breaks; any areas that are not sufficiently flat are treated with retinal cryopexy. Long-acting gas or silicone oil is injected into the vitreous cavity. A scleral buckle to support the vitreous base may also be placed. Reported complications of this approach include cataract, epiretinal membrane, and proliferative vitreoretinopathy requiring additional surgery.

REFERENCES

Ambler JS, Meyers SM, Zegarra H, et al: The management of retinal detachment complicating degenerative retinoschisis. Am J Ophthalmol 107:171– 176, 1989.

Byer NE: Clinical study of senile retinoschisis. Arch Ophthalmol 79:36–44, 1968.

Byer NE: Long-term natural history study of senile retinoschisis with implications for management. Ophthalmology 93:1127–1137, 1986.

George NDL, Yates JRW, Moore AT: Clinical features in affected males with X-linked retinoschisis. Arch Ophthalmol 114:274–280, 1996.

Sneed SR, Bodi CF, Folk JC, et al: Pars plana vitrectomy in the management of retinal detachments associated with degenerative retinoschisis. Ophthalmology 97:470–474, 1990.

329 ACUTE RETINAL NECROSIS

362.84

(Necrotizing Herpetic Retinopathy)

Mark S. Blumenkranz, MD

Menlo Park, California

Acute retinal necrosis is an ocular viral syndrome predominantly affecting the retina that is associated with four cardinal features:

●Confluent peripheral retinal necrosis with discrete borders associated with rapid circumferential progression in untreated eyes;

●Occlusive vasculopathy with predominantly arteriolar involvement;

●Vitreous and anterior chamber inflammation;

●Variable optic neuropathy.

If untreated, the disease is associated with rapid progression and severe vision loss, with bilaterality common. If untreated, more than three-fourths of patients will develop complex forms of retinal detachment and severe vision loss.

ETIOLOGY/INCIDENCE

The disease is thought to be caused by recrudescence of infection in the retina and adjacent ocular tissues with members of the herpes simplex virus-most typically herpes varicella virus and less often herpes simplex viruses I and II in immunocompetent individuals. Most cases are thought to represent reactivation of dormant virus from the dorsal root ganglia followed by hematogenous or neurotransmission spread to the eye. The distribution of the disease appears to be worldwide, wit an annual approximate calculated incidence of 4.25 in 1 million population in one study. This represents approximately 2.5% of the patients with uveitis seen at a large referral center. Males are thought to be more commonly affected than females, representing approximately two-thirds of reported cases. HLA phenotypes Bw62, DR4, and HLA-DR9 have been associated with increased frequency and severity of disease.

COURSE/PROGNOSIS

The course of untreated acute retinal necrosis is usually unfavorable in most patients; if the disease is untreated, most

patients develop extensive zones of confluent necrotizing retinitis, optic neuropathy, and, ultimately, retinal detachment (more than 75% of patients). Most commonly, there is a documented history of antecedent infection with herpes simplex, herpes varicella zoster, or simplex virus, although this may be remote, dating back to childhood chickenpox. A mild or limited form of acute retinal necrosis may follow acute herpes varicella zoster virus infection (chickenpox), particularly in adults, but this is exceedingly rare in children. A particularly severe form of acute retinal necrosis with distinctive features, termed progressive outer retinal necrosis, may occur in immunocompromised patients, particularly those with human immunodeficiency virus (HIV) infection. However, most patients with acute retinal necrosis are immunologically normal and have no immediate active preceding infection, although the necrosis occasionally follows an episode of shingles. With modern therapy, including antiviral drugs, anti-inflammatory medications, antithrombotic therapy, and laser prophylaxis, many of the most severe complications of the disease can be ameliorated or prevented.

DIAGNOSIS

Laboratory findings

The diagnosis is generally established on the basis of the characteristic slit-lamp and ophthalmoscopic findings, including:

●Acute vision loss secondary to vitreous inflammation, retinitis, and optic neuropathy, to varying degrees;

●Pain secondary to anterior uveitis or scleritis;

●Peripheral confluent zones of creamy-appearing necrotizing retinitis with dentate margins and circumferential spread;

●Obliterative vasculopathy-predominantly arteriolar sheathing and occlusion with associated peripheral retinal capillary nonperfusion.

Laboratory findings may demonstrate evidence of a previous infection with herpes varicella zoster or herpes simplex virus, although acute rises in titers of IgM to either agent are uncommon. Direct sampling of intraocular fluid by conventional viral culture techniques, and particularly polymerase chain reaction methods, may be useful although it is generally not required to establish the diagnosis.

●Suggested laboratory evaluation should exclude other treatable infectious processes and specific immunologic syndromes and should include complete blood cell count, sedimentation rate, antinuclear antibody, rheumatoid factor, VDRL syphilis test, fluorescent treponemal antibody absorption test, neurologic studies for HIV, blood urea nitrogen, creatinine, urinalysis, chest radiograph, and skin testing with purified protein derivative (PPD), in addition to serologic studies for evidence of prior infection with herpes simplex virus, herpes varicella zoster virus, and cytomegalovirus.

●In patients with severe vision loss out of proportion to ophthalmologic findings or other symptoms, including headache, change in mental status, or dermatologic manifestations of viral infection, optional tests may include computed tomography or magnetic resonance imaging of the orbit and optic nerve, aqueous tap for assessment of intraocular antibody production of herpes viruses and herpes viral DNA by polymerase chain reaction (if available), and vitrectomy in severe cases associated with atypical clinical presentation,

329 CHAPTERNecrosis Retinal Acute •

Retina • 30 SECTION

associated immunocompromise, or retinal detachment or in patients found to be resistant to initial therapy.

Differential diagnosis

●Syphilitic neuroretinitis.

●Cytomegalovirus retinitis.

●Toxoplasmic retinal choroiditis.

●Candida albicans endophthalmitis.

●Acute multifocal hemorrhagic retinal vasculitis.

●Behçet’s disease.

●Sarcoidosis.

●Ocular lymphoblastic lymphoma.

PROPHYLAXIS

There is no generally accepted prophylaxis for the development of disease in the first eye, but the use of intravenous and oral aciclovir, valciclovir or famciclovir and possibly other antiviral agents, is thought to be protective against the subsequent development of viral infection of the fellow eye in patients who present initially with unilateral disease. In addition, in patients who have active necrotizing retinitis, barrier peripheral laser photocoagulation of the retina may be effective in preventing the later development of retinal detachment.

Retinal detachment prophylaxis

Ultimately, the most frequent cause of vision loss in patients with acute retinal necrosis is late retinal detachment commonly associated with proliferative vitreoretinopathy. The use of peripheral laser photocoagulation to demarcate zones of anterior necrotic retina from the remainder of the retina appears to be beneficial in reducing the likelihood of this complication. In one series, only 17% of patients receiving laser photocoagulation developed retinal detachment, compared with approximately two-thirds of patients not receiving photocoagulation. The photocoagulation is limited to the anterior periphery and demarcates zones of necrotic retina in a nonspecific, diffuse panretinal pattern. Because patients may have associated pain and media opacities, retrobulbar anesthesia and the use of longer wavelengths, particularly yellow, red, and infrared, may be helpful. Patients with more severe intraocular inflammation may not have sufficient media clarity to permit this and therefore may be at higher risk for retinal detachment. The benefits of prophylactic vitrectomy and photocoagulation for this condition have not been established, nor have the prophylactic effects of scleral buckling, although this may be of value when media opacities prevent prophylactic photocoagulation.

TREATMENT

Systemic

The mainstay of treatment for this condition is antiviral therapy directed against members of the herpes simplex virus family. The traditional drug of choice is 1500 mg/m2/day aciclovir IV in three divided daily doses. Aciclovir is active against both herpes simplex and herpes zoster virus at dosages thought to be achieved within the eye after intravenous administration. Aciclovir may also be administered via the oral route, although the efficacy of this route of administration has not been well established relative to intravenous aciclovir. More recently, valciclovir and famciclovir have surpassed oral aciclovir because

of superior bioavailability. The drug may be administered at a dosage of 1000 mg/day to 4 g/day IV and is available in either 200 or 800 mg strengths. After 7 to 10 days of intravenous administration, it is recommended that patients receive oral therapy for an additional 3 weeks because active viral particles have been identified in eyes that have received intravenous therapy for 1 week. Newer agents thought to have greater bioavailability than aciclovir via an oral route are available and may be substituted, although clinic experience remains limited with these agents; these include famciclovir, which has been found to be effective in the treatment of patients with acute herpes zoster in the prevention of postherpetic neuralgia in doses of 500 mg t.i.d. Valciclovir may also be administered at 1000 mg/day TID and is thought to be as effective as five daily doses of 800 mg of aciclovir in the treatment of cutaneous herpes zoster infection. One recent study suggested that 1000 mg/day of valciclovir (Valtrex) was as effective as intravenous aciclovir in a small series of patients.

Anti-inflammatories

The second component of therapy in this disease consists of reduction in intraocular inflammation, particularly in the vitreous cavity, to reduce the likelihood of subsequent vitreous scarring, contracture, and late retinal detachment. The administration of oral prednisone or equivalent corticosteroids in dosages of 0.5 to 1.5 mg/kg/day is recommended approximately 24 to 48 hours after the initiation of antiviral therapy, to be gradually tapered over 1 to 3 weeks. The exact duration of steroid therapy is dictated by the severity of the intraocular inflammation and any associated complications of therapy.

Antithrombotics

Because patients have visual loss associated with arteriolar occlusions in the retina and optic nerve, antiplatelet therapy with aspirin is thought to be potentially beneficial. Platelet hyperaggregation may be increased and can be treated with aspirin 500 to 650 mg/day. The use of more aggressive forms of anticoagulation, including heparin or Coumadin, does not appear to be warranted.

Ocular

Most patients have associated anterior granulomatous uveitis, including keratic precipitates and anterior chamber cell and flare, often related to fibrinoid changes in the aqueous. Topical steroids and cycloplegics are useful in reducing pain and inflammation; the use of topical antiviral agents is not considered necessary.

Surgical

In patients who develop retinal detachment, vitrectomy can be of benefit in reattaching the retina and improving vision. Previous studies suggest that although scleral buckling may be effective in some patients, vitrectomy is required to relieve vitreoretinal traction and permit optimal tamponade with either gas (preferably) or silicone oil (if necessary) in patients due to the large number, size, and posterior extent of retinal breaks. The use of a supplementary scleral buckle associated with vitrectomy may be associated with ocular complications, including ocular hypertension, fibrin syndrome, and choroidal detachment. This is not absolutely required in patients in whom adequate vitreous traction release associated with photocoagulation and long-term tamponade can be achieved, although it is not contraindicated.

COMPLICATIONS

The principal complications are complex retinal detachment associated with proliferative vitreoretinopathy, optic atrophy, cataract, macular epiretinal membrane, and hypotony. Giant tears of the retinal pigment epithelium have been described, and patients with severe intractable inflammation or irreparable retinal detachment frequently develop phthisis bulbi.

REFERENCES

Aslanides IM, de Souza S, Wong D, et al: Oral valacylovir in the treatment of acute retinal necrosis. Retina 22:352–354, 2002.

Blumenkranz MS, Clarkson J, Culbertson WW, et al: visual results in complications after retinal reattachment in the ARN syndrome: the influence of operative technique. Retina 9:170–174, 1989.

Blumenkranz MS, Culbertson WW, Clarkson JG, et al: Treatment of the ARN syndrome with intravenous acyclovir. Ophthalmology 93:296– 300, 1986.

Culbertson WW, Blumenkranz MS, Haines H, et al: The ARN syndrome. Part 2: histopathology and etiology. Ophthalmology 89:1317–1325, 1982.

Duker JS, Blumenkranz MS: Diagnosis and management of the ARN syndrome. Surv Ophthalmol 35:327–343, 1991.

Engstrom RE, Holland GN, Margolis TP, et al: The progressive outer retinal necrosis syndrome (PORN): a variant of necrotizing herpetic retinopathy in patients with AIDS. Ophthalmology 101:1488–1502, 1994.

Figueroa MS, Garabito I, Guiterrez C, et al: Famcicilovir for the treatment of ARN syndrome. Am J Ophthalmol 123:255–56, 1997.

330 BRANCH RETINAL VEIN

OCCLUSION 362.36

Thomas Hwang, MD

Portland, Oregon

Michael Klein, MD

Portland, Oregon

ETIOLOGY/INCIDENCE

Branch retinal vein occlusion (BRVO) is a common disorder characterized by downstream effects of blocked blood flow in a branch retinal vein. The blockage most frequently occurs at an arteriovenous intersection. Rarely, an underlying inflammatory condition may cause secondary branch retinal vein occlusion in locations other than arteriovenous crossings.

It is thought that venous occlusion results in increased capillary pressure and subsequent damage of the capillaries, resulting in ischemia. The exact mechanism for this process is not clearly understood. One important response to ischemia is production of vascular endothelial growth factor (VEGF), which promotes vascular permeability and neovascularization. Capillary damage and increased hydrostatic pressure combined with factors such as VEGF result in leakage and retinal edema. Ischemia, retinal edema, and retinal neovascularization are the major causes of vision loss from BRVO.

Population based studies have found the prevalence of BRVO to be 0.6–1.0%, depending on the age distribution of the group being studied. The condition occurs more frequently in older patients, usually in the seventh decade of life. Hypertension is

a consistent risk factor found across multiple studies. Other risk factors, such as glaucoma, diabetes, smoking, cardiovascular disease, and body mass index, are reported by some but not by all.

COURSE/PROGNOSIS

The natural history of a branch retinal vein occlusion varies widely. In some patients, it may be an incidental finding without any symptoms. The location and the extent of retinal involvement as well as perfusion status are important determinants of the prognosis. Vision loss usually results from macular edema, macular ischemia, or complications of neovascularization, including vitreous hemorrhage, traction detachment, and rubeosis irides. The overall prognosis is good for patients with branch retinal vein occlusion, as 50–60% will maintain visual acuity of 20/40 or better after one year.

DIAGNOSIS

Clinical signs and symptoms

Patients with branch retinal vein occlusion usually present with decreased vision. The hallmark of an acute branch retinal vein occlusion is intraretinal hemorrhages in the territory of a retinal vein branch (Figure 330.1). Nerve fiber layer infarcts, retinal edema, intraretinal lipid exudation, and venous dilation and tortuosity are also commonly seen. Branch retinal vein occlusions of the superotemporal quadrant are most frequently found, but occlusions involving the nasal quadrants probably present rarely to the ophthalmologist.

With time, the intraretinal hemorrhages resolve. Sclerosis of both arterioles and venules in the affected area, telangiectaticappearing vessels-which may represent capillary dilation or

FIGURE 330.1. Branch retinal vein occlusion.

Occlusion330 CHAPTERVein Retinal Branch •

Retina • 30 SECTION

collaterals and microaneurysms are common findings in patients with chronic BRVO. Without the characteristic intraretinal hemorrhages, diagnosis of a chronic branch retinal vein occlusion can be challenging.

Vision loss in branch retinal vein occlusion is caused by macular edema, macular ischemia and neovascular complications. Macular edema may be present in both acute and chronic phases of the disease. Occasionally, distant peripheral vein occlusion can result in macular edema, supposedly mediated by factors such as VEGF.

Eyes with significant capillary non-perfusion may develop retinal neovascularization, and some of these will develop vitreous hemorrhage. Rubeosis irides is an infrequent but serious complication of branch retinal vein occlusion, occurring in about 1% of affected eyes.

Laboratory findings

When patients with branch retinal vein occlusion present with extensive retinal hemorrhages, ancillary testing such as fluorescein angiography is not useful, as the hemorrhages obscure too much of the retinal vasculature.

Once the hemorrhages have cleared sufficiently, a highquality fluorescein angiogram should be obtained to determine the perfusion status. Non-perfused branch retinal vein occlusions, or those with five or more areas of retinal capillary nonperfusion, have a 40% chance of retinal neovascularization. Sixty percent of these patients may develop vitreous hemorrhage. Those with perfused branch retinal vein occlusion are thought to be at low risk for neovascular complications.

The angiographic appearance of the parafoveal capillaries can guide determination whether the vision is limited by perfused edema or ischemic changes. A branch retinal vein occlusion is considered to have perfused edema when the parafoveal capillary network is intact and leakage is present from the vessels. This determination is particularly important for patients being considered for grid laser photocoagulation (see below) as the Branch Vein Occlusion Study results can only be applied to those patients with perfused edema.

Fluorescein angiography could also be helpful in situations when telangiectatic vessels are present. The characteristic appearance of collateral vessels can help make a diagnosis of chronic branch retinal vein occlusion. In those situations when clinical determination of neovascularization versus telangiectatic vessels is impossible, marked, early angiographic leakage from the vessels can help make a diagnosis of neovascularization.

High-resolution optical coherence tomography (OCT) is helpful in following retinal edema in the setting of branch retinal vein occlusion. Objective and quantitative retinal thickness measurements can aid in treatment decision making, especially when newer pharmacologic agents are considered.

Differential diagnosis

Diabetic retinopathy and hypertensive retinopathy can have many of the characteristics of branch retinal vein occlusion, including intraretinal hemorrhages, nerve fiber layer infarcts, macular edema, lipid exudation and retinal neovascularization. Branch retinal vein occlusions differ from those conditions in their localization along a retinal vein territory.

Retinal vasculitides with venous involvement, such as sarcoidosis and Eales disease, may have some features of vein occlusion, such as venous sheathing and tortunosity. They may also have associated branch retinal vein occlusions. These underlying conditions should be considered, especially when

branch retinal vein occlusion occurs in atypical locations, i.e. away from arteriovenous crossings.

Patients with retinal macroaneurysms may present with retinal hemorrhages and macular edema that appear to follow a vascular territory. This condition is also associated with hypertension. Fluorescein angiography may be helpful in identifying macroaneurysms. Branch retinal vein occlusion may occur concurrently as a result of a macroaneurysm.

Sclerotic arterioles of chronic branch retinal vein occlusion can be mistaken for old branch artery occlusion. Associated telangiectatic changes of the vessels are usually not present with arterial occlusion.

The telangiectatic-appearing vessels of a chronic branch retinal vein occlusion can mimic the appearance of idiopathic parafoveal retinal telangiectasis and the two can be difficult to differentiate. While many cases can be distinguished based on location, history and longitudinal follow-up may be necessary in others.

Sometimes the same telangiectatic-appearing vessels as appear in BRVO are mistaken for intraretinal microvascular abnormalities (IRMA) of diabetic retinopathy. Although the two conditions both cause dilated, tortuous intraretinal capillaries, IRMA in diabetic retinopathy is usually not concentrated in a quadrant along a vascular territory.

PROPHYLAXIS

No effective means of prophylaxis is known.

TREATMENT

Systemic

Systemic anticoagulation has not been shown to prevent or affect the clinical course of branch retinal vein occlusion and is not recommended at this time.

Ocular

Most treatments for BRVO are aimed at specific visionthreatening complications of the disease. Limited surgical options have been tried to reverse the underlying vascular occlusion and thus eliminate the inciting causes of those downstream complications. They are discussed in the following sections.

Medical

Pharmacotherapy for BRVO is aimed at treating macular edema. Although the Collaborative Branch Vein Occlusion Study (BVOS) has shown that grid laser photocoagulation is effective for increasing the chances of visual improvement with treatment for perfused macular edema (discussed below), there remained many eyes that did not respond to laser treatment or the results of the BVOS could not be applied.

There is most published experience with intravitreal corticosteroids, particularly triamcinolone acetonide. The actions of corticosteroids are multiple and non-specific, but include reduction of vascular permeability. Many have reported significant and sometimes dramatic improvement in vision and macular thickness with intravitreal triamcinolone acetonide at doses ranging from 2 to 25 mg. At least temporary improvement of vision and OCT evidence of decreased retinal thickness were seen in eyes that did not respond to BVOS-style laser or meet the criteria for grid laser.

Patients with persistent macular edema following laser photocoagulation could be considered for treatment with intravitreal triamcinolone acetonide. Eyes that are not eligible for BVOS grid laser because they have ischemic edema should first be observed, since spontaneous resolution of edema may be more frequent in these eyes than those with perfused edema.

Typically, the eye is anesthetized with subconjunctival lidocaine or with lidocaine gel. Superior anesthesia is achieved when lidocaine is left in place for several minutes. A solution of 5% povodine iodine is applied to the conjunctiva before the application of lidocaine gel, if used. With a lid speculum in place, a 27 g or 30 g needle is used to inject 0.1 cc of 40 mg/cc suspension of triamcinolone acetate into the vitreous through the pars plana. (The pars plana is measured 3.5 mm behind the limbus with calipers.) After injection, the speculum is removed and indirect ophthalmoscopy is performed to confirm perfusion of the optic nerve and alert the clinician to any immediate complications. Occasionally a paracentesis is necessary to bring the intraocular pressure to a safe level. Intraocular pressure is checked 10–20 minutes after the procedure. Many practioners routinely recommend antibiotic drops 4 times a day for 3 days, despite lack of evidence for their effectiveness in preventing endophthalmitis. Patients are discharged with instructions to return immediately if they have increased pain and decreased vision. The intraocular pressure should be checked in approximately 3 weeks, as steroid-induced pressure response is typically seen in this time frame.

Enthusiasm for intravitreal injection of triamcinolone acetonide is tempered by its many limitations. Even in cases with the most dramatic positive effect, the duration of this effect is limited. In a non-vitrectomized eye, the effect seems to last about 3 months, although the observed duration is highly variable. The effect is more abbreviated for vitrectomized eyes. Accelerated cataract formation is a frequent complication. Steroid-induced ocular hypertension occurs in about one-third of patients. While most can be treated with topical medications, a few need surgical treatment to relieve unacceptably high intraocular pressure. Multi-centered controlled clinical trials are under way to evaluate the efficacy and safety of intravitreal triamcinolone acetonide versus the current standard of care. Similar trials are being conducted for sustained-release corticosteroids.

Drugs with specific anti-VEGF activity are also being studied for treatment of macular edema caused by BRVO. Agents such as pegaptanib sodium, bevacizumab, ranibizumab, and anecortave acetate have the potential to decrease vascular permeability and reduce macular edema without the adverse effects of corticosteroid therapy. No medication, however, including triamcinolone acetonide, has been approved for use in treatment of macular edema caused by BRVO.

Surgical

Laser photocoagulation

Recommendations for laser photocoagulation are based on the Collaborative Branch Vein Occlusion Study (BVOS), a multicenter, randomized clinical trial sponsored by the National Eye Institute. The mechanism through which laser photocoagulation works is not clearly understood.

●Grid laser photocoagulation for macular edema: BVOS found that BRVO patients with persistent, perfused macular edema confirmed by high-quality fluorescein angiogram, vision 20/40 or worse, and vein occlusion of 3 to 18 months’ duration were twice as likely (63% vs. 36%) to gain 2 or more

lines of vision with grid laser photocoagulation at 3 years compared to observation. It is important to wait 3 to 6 months after the onset of disease to allow for clearing of hemorrhage, as hemorrhage can obscure adequate view for fluorescein angiogram, and laser photocoagulation through heme is theoretically more likely to result in complications. Also, as many eyes spontaneously improve in the first few months, waiting can obviate unnecessary treatment.

The protocol laser photocoagulation was performed in a grid pattern with argon blue-green laser, in the territory of the vein occlusion, between the major arcades and the foveal avascular zone. Recommended treatment parameters were duration of 0.1 second, 100 micron spot size and power setting sufficient to produce ‘medium’ white burn.

For patients who meet the above criteria, this treatment should certainly be considered, as its use is supported by the best evidence available for treatment of BRVO-related macular edema. Many experts warn not to extrapolate the results to patients who fall outside of the inclusion criteria for BVOS, particularly those with vision better than 20/40, non-perfused edema, and insufficiently cleared hemorrhages.

●Scatter laser photocoagulation: BVOS found that BRVO patients with 5 or more disc areas of non-perfusion had a 41% chance of developing retinal neovascularization, usually in the first 6 to 12 months after occlusion. Prophylactic scatter laser photocoagulation in the affected territory was found to reduce the incidence of neovascularization by 50%. However, prophylactic treatment is not routinely recommended, as many eyes (60%) would be treated unnecessarily.

Scatter laser photocoagulation is recommended when retinal neovascularization is found, as 60% of untreated eyes go on to develop vitreous hemorrhage. Treatment reduces the risk by 50%. Recommended parameters for treatment includes peripheral scatter with argon blue-green laser, spot size between 200– 500 microns, duration of 0.1 second, and power setting sufficient to produce a medium white burn.

Vitrectomy with or without sheathotomy

Since BRVO occurs at arteriovenous crossings in patients with increased risk for arteriolar disease, and at such crossings the sheath is shared by the arteriole and the venule, liberating the vessels from the confining sheath may theoretically improve blood flow through the venule and reverse some of the downstream effects of a vein occlusion. This technique has been tried by a few surgeons but has not been adopted by many.

A recent report has suggested that vitrectomy without sheathotomy may be as effective in improving vision in patients with macular edema and BRVO as vitrectomy with sheathotomy. It is difficult to say whether the improvement in vision in these reports represents truly superior results from laser photocoagulation, since many patients in these series had contemporaneous cataract surgery and treatment with triamcinolone acetonide. More studies are necessary to determine whether these surgical treatments are beneficial in this setting.

COMMENTS

Treatment for macular edema caused by BRVO is evolving. Currently, laser photocoagulation is the only proven treatment available for this condition. Alternative treatments that may

Occlusion330 CHAPTERVein Retinal Branch •

Retina • 30 SECTION

partial pressure of oxygen from the patent choroidal circulation to the retina after CRAO is adequate for prolonged survival but not for sustained physiological viability of the inner two-thirds of the retina. Experimental complete occlusion of the central retinal artery in rhesus monkeys for longer than 97 minutes resulted in irreversible retinal damage which became massive by 240 minutes.

Clinically, the patient’s CRAO may not be complete, in which case recovery of partial vision may occur hours or days after the onset of symptoms. The prognosis for visual recovery varies with the site of occlusion, being worse with more proximal occlusions such as those in CRAO and better with the distal occlusions seen in BRAO.

In CRAO, 70% of eyes have a final vision of 20/400 or worse. In contrast, 90% of eyes with BRAO retain vision of 20/40 or better.

DIAGNOSIS

Clinical signs

●In CRAO a relative afferent pupillary defect is almost invariably present. Retinal whitening and edema are visible, with maximal whiteness occurring approximately 70 minutes after deprivation of blood flow through the central retinal artery. Intracellular edema does not occur at the fovea which is devoid of ganglion cells. The characteristic cherry-red or brown spot occurs because the light reflex from the intact choroidal vessels remains visible at the fovea (Figure 331.1). The affected retinal arteries may appear thin and empty or have pulsatile or stationary blood segments that look like ‘boxcars’ or ‘cattle trucking.’ The veins are darker than normal due to stagnation of blood and poor oxygenation. Approximately one-third of patients have incomplete occlusion of the central retinal artery with some oxygenated blood flow to the retina; the presenting visual acuity in these patients may range from 20/30 to hand motion. When occlusion is incomplete, final visual acuity correlates positively with visual acuity at presentation and negatively with duration of visual impairment.

FIGURE 331.1. A color fundus photograph of a patients right eye showing the classical appearance of a central retinal artery occlusion with diffuse retinal whitening sparing the fovea and the resultant cherry red spot.

●In BRAO the retinal whitening is in the distribution of the affected artery (Figure 331.2). The site of the obstruction is most often at the bifurcation of the arteries where emboli are likely to become lodged. Arterial abnormalities similar to those in CRAO may be observed and emboli are visible in more than half of all eyes with BRAO.

Cholesterol emboli, also known as Hollenhorst plaques, are bright-yellow refractile crystals (Figure 331.3). Platelet-fibrin emboli are barely visible, grayish, nonrefractile plugs that tend to be mobile. Calcific emboli are large, white, oval, moderately refractile bodies at or near the optic disk.

Laboratory findings

●As one of the most dramatic sights in ophthalmology, the diagnosis is usually made clinically and, in the case of acute

FIGURE 331.2. A color fundus photograph of a patients right eye showing the area of retinal whitening corresponding to the area of retina affected by the branch retinal artery occlusion. An embolus is clearly visible within the vessel.

FIGURE 331.3. A color fundus photograph of a patients left eye showing a large Hollenhorst plaque within the central retinal artery resulting in a central retinal artery occlusion.

Occlusion Arterial331RetinalCHAPTERBranch or Central •

Retina • 30 SECTION

CRAO, prompt treatment is instituted. Laboratory studies may help determine the etiology of the occlusion but rarely affect the emergency room treatment.

●Obtain a CBC for baseline and check ESR and CRP to exclude an inflammatory endarteritis such as giant cell arteritis.

●Obtain fasting blood sugar, cholesterol, triglyceride and lipid panels to screen for atherosclerotic disease.

●Coagulopathy screen and blood cultures can identify more unusual causes.

●Arrange carotid Doppler ultrasound or magnetic resonance angiogram to evaluate for carotid disease.

●Echocardiogram and ECG (possibly a 24-hour ECG if paroxysmal atrial fibrillation is suspected) can be ordered for detection of structural abnormalities of the heart and arrhythmias.

●Electroretinogram (ERG) can serve to determine whether ophthalmic artery occlusion is present in addition to CRAO. In a pure CRAO, the B wave is lost as a result of inner retinal ischemia, but the A wave remains because the photoreceptors still function (intact choroidal circulation maintains oxygenation of the outer third of the retina). With ophthalmic artery occlusion or infarction of retinal and choroidal circulation from extraocular pressure, both the A and B waves of the ERG are lost.

●Fluorescein angiography may show a normal or delayed arm-to-retina circulation time. There may be slowing or even cessation of retinal arterial filling, corresponding to the site of occlusion. Increased arteriovenous transit time and attenuation of the vasculature are other features seen. With reperfusion, the fluorescein angiogram may return to normal despite persistently decreased vision.

Differential diagnosis

●Ophthalmic artery occlusion results in nonperfusion of the choroidal and retinal circulations. The presenting visual acuity is usually worse than that of CRAO, usually in the range of light perception to no light perception. Because of choroidal non-perfusion there usually is no cherry-red spot in the macula.

●A cherry-red spot is the most striking retinal lesion seen in the sphingolipidoses, a rare group of inherited metabolic disorders. Lipids are stored in the ganglion cells of the retina, giving a white appearance absent at the fovea. These disorders are usually seen bilaterally in the pediatric population and include Tay-Sachs disease and Niemann-Pick and Sandhoff disease. Their appearances may mimic CRAO but they are bilateral.

PROPHYLAXIS

The individual cause of an arterial occlusion often remains obscure but cardiovascular risk factors may be addressed to improve the patient’s systemic condition and minimize the risk of ocular and non-ocular sequelae. These include smoking, hypertension, hypercholesterolemia, diabetes, coronary artery disease or history of stroke/TIA.

The iatrogenic causes can be anticipated, and surgical procedures should be altered to reduce the risk of occlusion. For example, after a scleral buckle is placed, the patency of the central retinal artery should be verified by indirect ophthalmoscopy.

TREATMENT

Systemic

Possible underlying causes of retinal artery occlusion are evaluated and treated directly.

●If temporal arteritis is the cause of the retinal artery occlusion, high-dose corticosteroids should be started to prevent visual loss in the fellow eye.

●Hemodynamically significant atherosclerotic carotid disease may be amenable to surgery such as carotid endarterectomy or may be treated by an antiplatelet regimen.

●Anticoagulation has a role to play in treating occlusion due to thrombophilia or other pro-coagulopathies such as in the antiphospholipid syndrome (probably an important cause of retinal vascular occlusion in young patients).

Ocular

In BRAO, most patients regain good vision; therefore, treatment is of questionable value, especially because no treatment is of proven therapeutic benefit.

With CRAO, prompt intervention, preferably within 100 minutes of the onset of symptoms, improves the chance for visual recovery and long term ocular prognosis. Complete occlusion for more than 6 hours probably produces irreversible retinal damage, but most clinicians still recommend treatment if the CRAO is of less than 24 hours’ duration. The goal of the treatment is to restore blood flow and prevent irreversible retinal cell death by dislodging the emboli. Treatment modalities can be divided into medical and interventional.

Medical

●Acetazolamide 500 mg IV, to lower intraocular pressure relatively rapidly, thereby increasing the intravascular pressure gradient across the embolus and theoretically allowing dislodgment of any embolus downstream.

●Digital ocular massage to enhance aqueous humor outflow, followed by the abrupt release of pressure, increases the pressure gradient across the obstruction. This sudden change has the potential to mechanically dislodge the embolus.

●Hyperbaric oxygen, if instituted between 2 and 12 hours after onet, may be beneficial but transport to a chamber can waste precious time

●Hyperoxia during CRAO is associated with improved electroretinogram recovery in cats. It is probably worthwhile to start hyperoxia whilst other treatments are given.

●Carbogen, a mixture of 95% oxygen and 5% carbon dioxide, inhaled for 10 minutes every 2 hours for up to 48 hours, may induce retinal vasodilatation and increase oxygenation and retinal blood flow.

Surgical

●Anterior chamber paracentesis, using a 30-gauge needle to remove approximately 0.1 to 0.4 mL of aqueous humor, also abruptly lowers the intraocular pressure. The procedure may be carried out in the office at the slit lamp as long as aseptic technique is ensured.

●Local intraarterial fibrinolysis (LIF) by injection of urokinase or recombinant tissue plasminogen activator into the proximal part of the ophthalmic artery may result in significantly improved outcome compared with conservative treatment. Thrombolytics are ideally delivered directly into the ophthalmic artery by transfemoral catheterization in a

procedure usually performed by an interventional radiologist, to reduce the risk of systemic side effects such as hemorrhagic stroke. As with all treatments for CRAO it is important for LIF to be initiated within the first few hours of occlusion, before irreversible damage has occurred.

COMPLICATIONS

Approximately 18% of all patients with CRAO develop rubeosis iridis, which often results in rubeotic glaucoma. Other complications depend on the cause of the arterial occlusion. For example if an embolus caused the occlusion, then further emboli could affect the fellow eye or lead to a cerebrovascular accident. Temporal arteritis can swiftly lead to blinding involvement of the other eye, usually within the first 6 weeks of the first occlusion. Giant cell arteritis is a systemic condition that can affect numerous end organs.

COMMENTS

In patients with BRAO or CRAO, the search for an associated systemic disease is crucial regardless of the ocular presentation. In one study, the expected survival time for patients with CRAO was 5.5 years compared with 15.4 years for an agematched control population. In another report, patients with retinal arterial emboli had a 56% mortality rate over 9 years compared with a 27% rate for age-matched control subjects without emboli.

While increased mortality secondary to fatal stroke has been shown in studies, the most common cause of death in this population is cardiovascular disease. A thorough medical workup can often lead to identification of underlying disorders. Clearly retinal arterial occlusion is a warning sign heralding the need for systemic evaluation and reduction of vasculopathic and cardiovascular risk factors. Expeditious treatment of these disorders may decrease the risk of complications and result in longer life expectancy.

REFERENCES

Augsburger JJ, Magargal LE: Visual prognosis following treatment of acute central retinal artery obstruction. Br J Ophthalmol 64:913–917, 1980.

Duker JS, Sivalingam A, Brown GC, et al: A prospective study of acute central retinal artery obstruction: The incidence of secondary ocular neovascularization. Arch Ophthalmol 109:339–342, 1991.

Ffytche TJ: A rationalization of treatment of central retinal artery occlusion. Trans Ophthalmol Soc UK 94:468–479, 1974.

Hayreh SS, Zimmerman MB, Kimura A, Sanon A: Central retinal artery occlusion. Retinal tolerance time. Exp Eye Research 78(3):723–736, 2004.

Schmidt D, Schulte-Monting J, Schumacher M: Prognosis of central retinal artery occlusion: local intraarterial fibrinolysis versus conservative treatment. Am J Neuroradiol. 23(8):1301–1307, 2002.

332 CENTRAL SEROUS CHORIORETINOPATHY 362.41

(Central Serous Retinopathy)

Christopher N. Singh, MD

Seattle, Washington

Peter N. Youssef, MD

Seattle, Washington

David A. Saperstein, MD

Seattle, Washington

ETIOLOGY/INCIDENCE

Central serous chorioretinopathy (CSC) is a disorder of the central macula. It is characterized by serous leakage from the choriocapillaris through the retinal pigment epithelium (RPE) leading to neurosensory retinal detachment (NSD) and occasionally RPE detachment. Hyperpermeability and leakage of the RPE and choriocapillaris can be demonstrated on fluorescein angiography (FA) and indocyanine green (ICG) angiography. The NSD can be visualized and quantitated using optical coherence tomography (OCT).

CSC typically affects people between the ages of 20 to 55 years old. There is a higher reported incidence among Caucasians, Hispanics and Asians, and a low occurrence rate in African Americans. Other risk factors, as described in retrospective studies, include male gender, corticosteroid use, pregnancy, ‘type A’ personality, psychological stress, and elevated levels of endogenous steroid, as in Cushing’s syndrome. Some evidence also exists for uncontrolled hypertension, allergic respiratory disease, antibiotic use, systemic lupus erythematosis, end-stage renal disease, gastroesophageal reflux disease, and the use of psychiatric medications as additional risk factors.

COURSE/PROGNOSIS

Presenting symptoms include decreased visual acuity, metamorphopsia, micropsia, central color vision deficiency, central scotoma, decrease in contrast sensitivity and increasing hyperopia. Presenting visual acuity deficits are usually mild. Patients presenting with 20/20 vision usually maintain that level. Patients with an initial visual acuity of 20/30 or worse tend to gain one to two lines of Snellen visual acuity upon resolution of the NSD.

The majority of patients with this disease will have resolution of the NSD in two to four months without treatment. Often resolution of visual symptoms and return of visual acuity to baseline or near baseline are attained, but may lag behind resolution of the NSD. One-third to one-half of patients will have chronic or recurrent NSD. Chronic NSD for a period of greater than 4 months can lead to foveal atrophy, as demonstrated on OCT studies. Foveal atrophy in these cases corresponds to lower final best-corrected visual acuity, regardless of anatomic reattachment.

Chorioretinopathy332 CHAPTERSerous Central •

Retina • 30 SECTION

Disease Coats’ • 333 CHAPTER