Retina • 30 SECTION

●Persistent hyperplastic primary vitreous.

●Intraocular toxocariasis.

●Congenital cataract.

●Familial exudative vitreoretinopathy.

●Retinal detachment.

●Eales disease.

●Branch retinal vein occlusion with secondary vascular leakage.

●Parafoveal telangiectasia.

●Intraocular tumor with exudation.

●Retinal angiomatosis.

TREATMENT

The patient may be followed conservatively if the lesions are limited and do not threaten the macular area.

The goal of treatment is obliteration of the vascular abnormalities to stop the exudation. More than one session might be necessary. It is important to treat the entire area of abnormal blood vessels.

Laser photocoagulation

●Preferred method of treatment.

●Leaking lesions treated directly.

●Treat mildly to avoid an exudative reaction (Coats’ response).

●Spot size of 200 to 500 μm.

●Duration of 0.2 to 0.5 second.

●Yellow or argon green dye.

●End point: spasm or whitening of the vascular anomalies.

Cryotherapy

●Useful when the retina is detached or lesions are far anterior.

●Double freeze-thaw technique.

●Treat directly on the abnormal vessels.

External drainage of the subretinal fluid

●Selected cases with bullous or total retinal detachments.

●With or without scleral buckle.

●Followed by laser photocoagulation or cryotherapy.

Vitrectomy

●Selected cases with bullous, total or tractional retinal detachments.

COMPLICATIONS

●Cystoid macular edema.

●Exudative retinal detachment.

●Neovascular glaucoma.

●Secondary angle-closure glaucoma.

●Iridocyclitis.

●Cataract.

●Phthisis bulbi.

REFERENCES

Coats G: Forms of retinal dysplasia with massive exudation. R Lond Ophthalmol Hosp Rep 17:440, 1908.

Kiratli H, Eldem B: Management of moderate to advanced Coats’ disease. Ophthalmologica 212:19–22, 1998.

Shields JA, Shields CL, Honavar SG, Demirci H: Clinical variations and complications of Coats disease in 150 cases: the 2000 Sanford Gifford Memorial Lecture. Am J Ophthalmol 131:561–571, 2001.

Shields JA, Shields CL: Review: Coats disease: the 2001 LuEsther T. Mertz lecture. Retina 22:80–91, 2002.

Shields JA, Shields CL, Honavar SG, et al: Classification and management of Coats disease: the 2000 Proctor Lecture. Am J Ophthalmol 131:572– 583, 2001.

334 DIFFUSE UNILATERAL SUBACUTE NEURORETINITIS

363.05

Geoffrey Emerson, MD, PhD

Portland, Oregon

Diffuse unilateral subacute neuroretinitis (DUSN) was first reported by Gass and Scelfo in 1978. The earliest described patients were otherwise healthy and presented with unilateral vision loss that often was severe and progressive. The ocular findings included vitritis, papillitis, arteriolar narrowing, and extensive retinal pigmentary change. The syndrome is now thought to be secondary to the presence of an intraretinal nematode. The ocular damage is believed to be secondary to the direct toxic effect of the worm and the ocular inflammatory reaction. Elimination of the nematode results in resolution of ocular inflammation and arrest of disease. Failure to eliminate the nematode results in progressive ocular destruction.

ETIOLOGY/INCIDENCE

Ocular larvae migrans of nematode origin have been associated with diffuse unilateral subacute neuroretinitis. A number of nematodes remain etiologic candidates in DUSN. Toxocara canis was the first worm to be considered, but more recently, Baylisascaris larvae, especially B. procyonis, which is found in raccoons, has been implicated. Ancylostoma caninum, Strongyloides spp. and Brugia malayi are also reported. Endemic areas of the United States for this disease include the southeast and Midwest. A heightened awareness of the disease has resulted in recent reports of DUSN in Canada, Brazil, Venezuela, the Caribbean, Senegal, and India. The nematode may persist in the fundus for up to 3 years; hence, the various sizes of the worm may be due to variations in its age. Evidence implicating multiple species is the finding that a larger worm is reported to predominate in the midwestern United States, whereas a smaller variety predominates in the southeastern United States. Despite the association, a worm is actually identified in only a minority of cases. It is the other clinical signs that usually lead to the diagnosis.

COURSE/PROGNOSIS

●Early characteristics include vision loss, mild vitritis, papillitis, and recurrent crops of gray-white lesions.

●Later characteristics include progressive visual loss, optic atrophy, and retinal vessel narrowing; diffuse pigment epithelial degeneration (‘wipeout’) may develop.

●Other clinical presentations include coarse clumping of subretinal pigment, which is occasionally arranged in a pattern suggesting ‘worm tracks,’ and scattered focal chorioretinal atrophic scars.

Neuroretinitis334SubacuteCHAPTERUnilateral Diffuse •

Retina • 30 SECTION

PROPHYLAXIS

No effective preventative measures are known for this condition.

TREATMENT

Systemic

No clear benefit has been shown from systemic therapy, including high-dose corticosteroids.

Surgical

The mainstay of treatment for Eales disease is scatter photocoagulation of the ischemic retina. Neovascular tissue regresses readily with this treatment, but vigilance is required as larger areas of ischemia may develop, resulting in further neovascularization. Some patients will go on to have non-clearing or repeated vitreous hemorrhage, or other complications of neovascularization such as traction retinal detachment. Pars plana vitrectomy is effective in treating these complications.

COMMENTS

Although considered a distinct entity with characteristic clinical, funduscopic, and fluorescein angiographic findings, Eales disease remains a diagnosis of exclusion, and other retinal causes of inflammation and neovascularization must be excluded.

REFERENCES

Biswas J, Therese L, Madhavan HN: Use of polymerase chain reaction in detection of Mycobacterium tyberculosis complex DNA from vitreous samples of Eales’ disease. Br J Ophthalmol 83(8):994, 1999.

Gass JDM: Macular dysfunction caused by retinal vascular diseases. In: Gass JDM, ed: Stereoscopic atlas of macular diseases diagnosis and treatment. vol. 1. St Louis, Mosby-Year Book, 1997:1:534–538.

Katz B, Wheeler D, Weinreib RN, et al: Eales’ disease with central nervous system infarction. Ann Ophthalmol 23(12):460–463, 1991.

Renie WA, Murphy RP, Anderson KC, et al: The evaluation of patients with Eales’ disease. Retina 3:243–248, 1983.

Smiddy WE, Isernhagen RD, Michels RG, et al: Vitrectomy for nondiabetic vitreous hemorrhage. Retinal and choroidal vascular disorders. Retina 8:88–95, 1988.

336 GYRATE ATROPHY OF THE CHOROID AND RETINA WITH HYPERORNITHINEMIA 363.57

(Ornithine- -Aminotransferase Deficiency)

La-ongsri Atchaneeyasakul, MD

Bangkok, Thailand

Richard G. Weleber, MD

Portland, Oregon

ETIOLOGY/INCIDENCE

Gyrate atrophy of the choroid and retina is a rare, autosomal recessive, progressive dystrophy that is associated with hyper-

ornithinemia and deficient activity of the mitochondrial matrix enzyme ornithine- -aminotransferase (OAT), a pyridoxal phos- phate-dependent enzyme required for the synthesis of proline from ornithine. Plasma, urine, spinal fluid, and aqueous humor levels of ornithine are 10 to 20 times higher than normal. The human OAT gene was mapped to chromosome 10q26, and multiple mutant alleles and compound heterozygotes have been described.

DIAGNOSIS

Clinical signs and symptoms

Ocular or periocular

●Choroid: atrophy.

●Iris: atrophy, loss of pigment.

●Lens: subcapsular cataracts (usually seen before the third decade of life).

●Optic nerve: pallor, peripapillary atrophy, astrocytic hamartoma of the optic disc.

●Retina: abnormal dark adaptometry, abnormal EOG, atrophy, epiretinal membrane, macular edema, retinal detachment, subnormal or nonrecordable ERG, traction schisis, vascular leakage and shunt vessels, vascular sheathing and attenuation.

●Vitreous: opacity, hemorrhage.

●Other: constriction of visual fields, decreased visual acuity, dyschromatopsia, moderate to high myopia.

Laboratory findings

The disease is characterized by circular patches of total vascular choroidal atrophy, which begin in the periphery in early childhood, enlarge and coalesce, and eventually extend toward the posterior pole. Constriction of the visual field, night blindness, cataracts (usually posterior subcapsular type), defective color vision, retinal vascular leakage, peripapillary atrophy, and macular changes develop as the disease progresses. Rarely, macular edema results. Myopia of a moderate to severe degree is frequent. Rhegmatogenous and nonrhegmatogenous retinal detachments have been described, along with the management. Legal blindness usually occurs in the fourth to fifth decade. Electroretinogram (ERG) responses and electro-oculogram (EOG) light-induced increases in the resting potential of the eye, as measured by the light-to-dark ratios, are consistently abnormal and eventually unrecordable by standard techniques. Studies in a mouse model suggested that retinal pigment epithelial cells are the initial site of pathologic changes. Seizures with or without abnormal electroencephalograms have been reported. Although the neuromuscular and electromyographic examinations are normal, eosinophilic subsarcolemmal deposits, which appear as tubular aggregates on electron microscopy, are seen on muscle biopsy. Skeletal muscle changes can also be demonstrated by computed tomography scanning and magnetic resonance imaging. They may be secondary to the inhibition of creatine synthesis by ornithine.

Parents who are carriers of this condition are normal clinically. Siblings may be affected and should be evaluated through the determination of serum ornithine levels and fundus examination because eye disease may be unrecognized. Prenatal diagnosis is possible by measuring OAT activity in cultured amniotic fluid cells or cultured chorionic villi. In families with a previous history of gyrate atrophy, the study of restriction fragment length polymorphism for OAT might be helpful for prenatal diagnosis and carrier detection.

Hyperornithinemia with Retina and Choroid336 CHAPTERthe of Atrophy Gyrate •

Retina • 30 SECTION

Disorders Degenerative Vitreoretinal and337BreaksCHAPTERRetinal Peripheral •

Retina • 30 SECTION

DIAGNOSIS

Most peripheral vitreoretinal degenerative disorders and retinal breaks exhibit characteristic distinguishing features.

Vitreoretinal disorders

Lattice degeneration usually occurs as oval-shaped areas of retinal thinning that are primarily located parallel to the ora serrata; however, some lesions are radial and associated with larger blood vessels. Varying degrees of pigmentation are seen around the margins, and criss-crossed areas of sclerotic vessels and atrophic holes also may be present within the margins of the lesions. Scleral depression usually reveals localized vitreous liquefaction over the lesions, and vitreoretinal adhesions are always present at the margins.

Cystic retinal tufts appear as discrete, sharply circumscribed opaque white or gray lesions, usually in the equatorial zones. Pigment alterations in the base of the lesion are frequent, and there commonly are significant vitreous condensations attached to the surface of the tuft.

White without pressure refers to sharply demarcated geographic areas of relative whiteness appearing to lie at the inner surface of the peripheral retina. It is probably a reflex related to relative youth and pigmentation of the patient.

Intraretinal disorders

Peripheral typical cystoid degeneration appears as a multitude of tiny cysts within the far peripheral retina. It most commonly is seen inferior temporally but can sometimes be seen for 360 degrees. Temporally, it frequently appears as a grayish band of irregularly surfaced retina.

Typical retinoschisis occurs when cysts of cystoid degeneration enlarge to more than 1.5 mm mm in diameter. It most commonly is seen inferior temporally. A cyst-like structure that cannot be decompressed with scleral depression is its most likely appearance. It usually occurs first in the inferotemporal quadrant. If the inner layer of retina is sufficiently elevated, retinoschisis can mimic the appearance of RRD.

Chorioretinal disorders

Paving-stone degeneration consists of one or more welldemarcated yellowish-white lesions that primarily occur very anteriorly in the inferior quadrants. These represent areas of atrophic outer retina, retinal pigment epithelium, and inner choroid.

Reticular chorioretinal pigmentary degeneration is a net-like subretinal pigmentary change in the equatorial retina, associated with equatorial drusen. Associated intraretinal and perivascular pigment spicules are occasionally observed.

Retinal breaks

Retinal tears are due to vitreoretinal traction on vitreoretinal adhesions. Horseshoe tears appear as retinal defects associated with U- or V-shaped flaps, with the bases located at the anterior edge of the break and the flap pointing posteriorly. An operculated tear results from a horseshoe tear that has an avulsed flap.

Atrophic holes are round or oval-shaped dehiscences in the retina that are found in lattice lesions or in isolated areas of the peripheral retina. A retinal dialysis appears as a circumferential break or disinsertion of the retina at or within one disk diameter of the ora serrata.

TREATMENT

Most contemporary preventative therapies have been proposed to reduce the frequency of retinal tears at sites of visible vitreoretinal adhesive lesions or to prevent the accumulation of subretinal fluid around retinal breaks. Treatment has usually consisted of creation of chorioretinal adhesions, with lasers or cryotherapy, around visible focal degenerative lesions or retinal breaks. Others have proposed creating a peripheral ring of chorioretinal adhesions to prevent the development of tears at sites of both visible and invisible vitreoretinal adhesions. The results of treating visible vitreoretinal adhesions, such as lattice degeneration, to prevent retinal detachment have been evaluated by expert panels, and the American Academy of Ophthalmology (AAO) has published a ‘Preferred Practice Pattern’ (PPP) regarding prophylactic therapy.

In the American Academy of Ophthalmology Preferred Practice Patterns (AAO PPP), no prospective randomized trials of preventative therapy of any vitreoretinal lesions, including all types of retinal breaks, were identified. In cases of prior retinal detachment due to lattice degeneration, there was ‘substantial’ evidence that treating lattice lesions in the fellow eye was of limited value. However, the same evidence demonstrated that such treatment was of no value if the degree of myopia exceeded -6 diopters or if there were more than 6 clock-hours of lattice degeneration. Thus, prophylactic therapy appears to be of less value in higher-risk cases, and the best evidence also indicated that there was ‘substantial’ evidence that routine treatment of lattice degeneration in non-fellow eyes was of no benefit.

The major limitation in treating visible vitreoretinal adhesions is that subsequent retinal tears and detachments occur in areas that appear normal prior to PVD. To accomplish a goal of treating invisible adhesions, some authors have recommended the placement of chorioretinal burns over a 360-degree zone of peripheral retina extending from the equator to the ora serrata, and both laser and cryotherapy has been employed for this purpose. Good evidence that this form of therapy is effective is currently lacking.

COMMENTS

Focal abnormalities in the peripheral retina are encountered frequently, but most are of no significance. Although lattice degeneration and retinal breaks are clearly associated with RRD, evidence for the value of treating these lesions in asymptomatic patients is currently lacking. The best management strategies should include thorough discussions with patients regarding (1) the presence of entities that may predispose to RRD, (2) the critical importance of the onset of symptoms suggestive of PVD, and (3) the need for periodic examinations.

REFERENCES

American Academy of Ophthalmology: Preferred practice pattern. posterior vitreous detachment, retinal breaks, and lattice degeneration. San Francisco, American Academy of Ophthalmology, 2003.

Byer NE: Cystic retinal tufts and their relationship to retinal detachment, Arch Ophthalmol 99:1788–1790, 1981.

Byer NE: Long term natural history of lattice degeneration of the retina. Ophthalmology 96:1396–1402, 1989.

Byer NE: Prognosis of asymptomatic retinal breaks. Arch Ophthalmol 92:208–210, 1974.

Byer NE: The natural history of asymptomatic retinal breaks. Ophthalmology 89:1033–1039, 1982.

Davis MD: The natural history of retinal breaks. Arch Ophthalmol 92:183– 194, 1974.

338 REFSUM’S DISEASE 356.3

(Heredopathia Atactica

Polyneuritiformis, Phytanic Acid

Oxidase Deficiency, Hereditary Motor

and Sensory Neuropathy IV, HMSN IV)

La-ongsri Atchaneeyasakul, MD

Bangkok, Thailand

Richard G. Weleber, MD

Portland, Oregon

ETIOLOGY/INCIDENCE

Refsum’s disease is a rare autosomal recessive disorder of lipid metabolism affecting mostly those of Scandinavian and Northern European descent. The deficiency of the peroxisomal enzyme phytanoyl-coenzyme A α-hydroxylase (PhyH), which catalyzes the a-oxidative process in phytanic acid catabolism, leads to the accumulation of the branched chain fatty acid phytanic acid in the serum and the tissues, with a predilection for adipose tissue, liver, and kidneys. The gene encoding PhyH (PHYH gene), located on chromosome 10p, has been identified, and different mutations have been demonstrated in patients with Refsum’s disease. Recently, linkage analysis of patients diagnosed with Refsum’s disease, but without mutations in PHYH, suggested a second locus on chromosome 6q22-24. This region includes the PEX7 gene, which codes for the peroxin 7 receptor protein required for peroxisomal import of proteins containing a peroxisomal targeting signal type 2. The age of onset of this disease varies from the first to the fifth decade of life.

DIAGNOSIS

This syndrome is characterized by atypical retinitis pigmentosa, chronic polyneuropathy, and cerebellar signs. Other clinical findings include congestive heart failure, nerve deafness, and ichthyosiform skin lesions. Skeletal abnormalities have been described in some cases, including multiple epiphyseal dysplasia and shortening of the fourth metatarsals.

Clinical signs and symptoms

Although phytanic acid is stored in fatty tissues, symptoms of the disease are related to the concentration of phytanic acid in the blood rather than total body stores. The earliest symptom is almost invariably night blindness, which usually occurs before the age of 20. Electroretinogram responses are profoundly abnormal or nondetectable, although there is a report of mild retinal changes in an older patient. The disturbance in retinal pigmentation, which early in the disease is often limited to the periphery, may be granular, rather than ‘bone-spicule.’ Weakness in the extremities, unsteadiness of gait, and a history of

chronic exacerbations and remissions are common. Complete external ophthalmoplegia and cataracts have been reported. Often, the diagnosis of Friedreich’s ataxia is entertained; however, tendon reflexes that are initially undetectable may return weeks or months later. Invariably, cerebrospinal fluid shows an elevation in protein content without pleocytosis. Histologic study of the peripheral nerves shows thickening and hypertrophy around the nerve roots and degeneration of nuclei and fiber tracts in the brain stem. Ichthyosiform skin lesions may wax and wane with the rising and falling of the serum phytanic acid level. Impairment of renal function has also been reported. Impaired atrioventricular conduction, bundle-branch blocks, and cardiac arrhythmia may have contributed to the occasional occurrence of sudden death.

Ocular or periocular

●Cornea: epithelial and stromal edema, hypertrophy of the corneal nerves, reduced corneal sensation.

●Eyelids: ptosis.

●Lens: cataracts (usually posterior subcapsular).

●Optic nerve: partial demyelination, atrophy.

●Pupils: miosis, poor reaction to light and accommodationconvergence, poor response to cycloplegic and mydriatic drugs.

●Retina: lipid deposits in pigment epithelium with degeneration of overlying photoreceptors.

●Sclera: lipid deposits.

●Other: lipid deposits in the iris pigment epithelium and trabecular meshwork, glaucoma, visual field constriction, nystagmus, progressive external ophthalmoplegia.

TREATMENT

When untreated, the life expectancy is shortened.

Systemic

Dietary restriction of phytanic acid

Because phytanic acid is not metabolized in patients with Refsum’s disease and the only source of phytanic acid in humans is dietary, restriction of oral intake of phytanic acid and, to a lesser extent, of phytol, which can be converted into phytanic acid, has been advised and found beneficial. Specifically, dietary intake of dairy products and fats and meats from ruminant animals, all of which contain phytanic acid, must be markedly curtailed. Caution should be observed to avoid starvation diets, as they can cause rapid mobilization of body stores of phytanic acid with a marked increase in the elevation of serum phytanic levels, acute toxicity, cardiac arrhythmias, and possible cardiac arrest.

Plasmapheresis

Plasmapheresis or plasma exchange is a useful treatment to lower plasma phytanic acid concentrations rapidly and has a definite role in the treatment of acute toxic states. Another procedure, called lipapheresis or cascade filtration, appears to be the treatment of choice to reduce plasma phytanic acid without the need for albumin replacement and also to reduce the loss of immunoglobulin.

Supportive

Carrier detection

Refsum’s disease is an autosomal recessive genetic trait. Carriers with dietary loading may show elevated phytanic acid levels.

338 CHAPTERDisease Refsum’s •

Retina • 30 SECTION

However, carrier detection is best determined by assay of phytanic acid a-oxidase activity in cultured skin fibroblasts.

Prenatal diagnosis

Because cultured amniocentesis cells show the enzyme activity, antenatal diagnosis of the affected or carrier state is theoretically possible.

COMMENTS

If started early, dietary restriction may prevent the development of neuromuscular and retinal changes. However, no conclusive evidence of improvement in cranial nerve and retinal function has been reported with dietary restriction or plasmapheresis. This lack of improvement may reflect the extent of irreversible damage to the retina. Early recognition and prompt treatment may forestall the development of these irreversible visual changes, although no improvement in the vision of patients with well-advanced disease should be expected. Because careful monitoring of diet and serum phytanic levels is required, these patients should be referred to tertiary medical centers for medical evaluation and therapy.

The diagnosis of Refsum disease might be delayed or misdiagnosed as Kearns-Sayre syndrome in a patient with the combined clinical features of ptosis, progressive external ophthalmoplegia, retinitis pigmentosa, and myocardiopathy. Such failure to make the correct diagnosis results in the delay in appropriate treatment.

Definite clinical and biochemical improvement has been reported with reduction of dietary phytanic acid and plasmapheresis. Muscle strength, tendon reflexes, sensory and motor nerve conduction, and certain objective tests of coordination have improved with treatment. The ichthyosiform rash and cardiac arrhythmias also clear as the serum phytanic acid decreases. One 39-year-old patient treated with dietary restriction over the past 13 years has shown only minimal progression of the visual findings during this period.

REFERENCES

Claridge KG, Gibberd FB, Sidey MC: Refsum disease: the presentation and ophthalmic aspects of Refsum disease in a series of 23 patients. Eye 6:371–375, 1992.

Gutsche HU, Siegmund JB, Hoppmann I: Lipapheresis: an immunoglobu- lin-sparing treatment for Refsum’s disease. Acta Neurol Scand 94:190– 193, 1996.

Jansen GA, Ofman R, FerdinanAusse S, et al: Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. Nat Genet 17:190– 193, 1997.

Jansen GA, Wanders RJ, Watkins PA, Mihalik SJ: Phytanoyl-coenzyme A hydroxylase deficiency: the enzyme defect in Refsum’s disease. N Engl J Med 337:133–134, 1997.

339 RETINAL DETACHMENT 361.9

Graham Duguid, MD, BMedBiol, FRCS

London, UK

Retinal detachment is the separation of the neurosensory retina from the adjacent retinal pigment epithelium. Retinal detachments can be classified into three groups: rhegmatogenous,

traction, and exudative. Rhegmatogenous retinal detachments are caused by the migration of vitreous cavity fluid through one or more holes or breaks in the retina. Traction retinal detachments are caused by the proliferation and contraction of fibrous or vascular scar tissue on the inner and / or outer surface of the retina. Exudative retinal detachments are caused by the leakage or production of fluid under the retina due to a diverse group of pathologic conditions. The successful treatment of retinal detachment is dependent on the identification of the underlying cause of the detachment. In complex cases, more than one pathologic mechanism may be present, such as a combined traction and rhegmatogenous retinal detachment in a patient with proliferative diabetic retinopathy.

ETIOLOGY

Rhegmatogenous retinal detachment

●This may occur with or without posterior vitreous detachment (PVD).

●A hole or tear develops in the retina.

●Retinal holes usually occur in an area of thinning such as retinal atrophy or lattice.

●Retinal tears are usually associated with posterior vitreous detachment and occur at an area of increased vitreo-retinal adhesion, often close to a retinal blood vessel.

●Attached vitreous gel can elevate the margin of the retinal tear.

●Fluid in the vitreous cavity migrates through the retinal defect and enters the potential space between the photoreceptor elements and the retinal pigment epithelium.

●The most important inherent predisposing factors are vitreous liquefaction, acute posterior vitreous detachment, abnormally firm vitreoretinal adhesion, lattice degeneration, cystic retinal tufts and myopia.

Traction retinal detachment

●The underlying disease process causes an inflammatory response affecting the posterior segment.

●Abnormal vitreous combines with breakdown of bloodretina barrier to initiate wound-healing response.

●Cells in the posterior segment migrate and proliferate.

● Proliferated cells attain critical mass and contract with a force exceeding the forces that maintain retinal attachment.

●The initiation of traction retinal detachment results in further inflammation and breakdown of the blood–retinal barrier, resulting in a vicious cycle that accelerates the detachment process.

●Alternatively, new blood vessels may grow from the retina onto the posterior hyaloid face, as in diabetic retinopathy or sickle-cell retinopathy.

●Traction may result anteroposteriorly from an incomplete posterior vitreous detachment or tangentially from contraction of the fibrovascular proliferation.

Exudative retinal detachment

●This results from the leakage or production of fluid in the subretinal space.

●Subretinal fluid usually originates from retinal or choroidal vasculature.

●There is a diverse spectrum of underlying pathology, including neoplasms, inflammatory disease, retinal vascular disease, and congenital disorders.

DIAGNOSIS

Clinical signs and symptoms

●The detailed history should include the present ocular symptoms, previous or concurrent ocular disease, and previous ocular trauma or surgery.

●Usually symptoms of floaters, photopsia and/or a peripheral visual field defect progressing centrally are described. The visual acuity may be reduced if the macula becomes involved.

●Past ophthalmic history should note any pre-exisiting eye disease, previous trauma or surgery. Any refractive error should be noted.

●A past medical history and review of systems, medications, and allergies should be included.

●The family history is important, especially with regard to the occurrence of retinal detachment in blood relatives.

●Comprehensive examination of both eyes should be done. Specific signs to be noted include, the visual acuity, the presence of a relative afferent pupil defect, the extent of any visual field defect, any intraocular inflammation, raised or lowered intraocular pressure, and the presence of any pigmented or white cells in the vitreous.

●A detailed evaluation of the retina using biomicroscopy and indirect ophthalmoscopy with scleral indentation is the most crucial portion of the examination.

●Critical features to identify during the retinal examination of the involved eye include the extent and topography of the retinal detachment, the type and location of all retinal breaks, presence of PVD, areas of persistent vitreoretinal traction, the presence and configuration of epiretinal membranes, the status of the optic nerve and macula, and any signs of conditions causing exudative retinal detachment.

●The retina of the fellow eye should be examined to look for PVD, asymptomatic retinal tears or detachments, lesions predisposing to rhegmatogenous detachments, proliferative retinopathy, or signs of systemic disease associated with exudative detachments.

Differential diagnosis

Rhegmatogenous retinal detachments

●There are convex surfaces and convex borders.

●Vitreous pigment cells are usually present (Schaffer’s sign).

●The presence of a retinal break is diagnostic of a rhegmatogenous detachment, although occasionally the hole or holes cannot be identified before or during surgery.

●Alternating retinal bullae and folds oriented in a radial direction from the optic disk to the ora serrata are present.

●The topography and extent of the detachment usually predict the location of the retinal break or breaks.

Traction retinal detachments

●There usually are concave surfaces and some concave borders.

●The configuration, site, and extent of the detachment can be accounted for by the manifest vitreous traction.

●Fibrous (PVR) membranes or neovascularisation may be present.

●Retinal holes or vitreal pigment are absent unless combined rhegmatogenous and traction detachment.

Exudative retinal detachments

●There are convex surfaces and convex boundaries.

●The subretinal fluid typically shifts to the portion of the eye that is dependent (e.g. a patient may have poor vision on awakening after sleeping in the supine position because the subretinal fluid detaches the macula).

●No retinal breaks are observed.

●Signs of the causative underlying disease are usually apparent in the affected eye or, in the case of a systemic condition, in both eyes.

Retinoschisis

●Usually convex borders and surfaces, and inferotemporal or superotemporal in location. Retina appears very thin and may have multiple small holes or white spots on inner surface.

●Patient is often hypermetropic and very rarely myopic.

●Associated visual field defect is absolute (rather than relative in retinal detachment.)

Investigations

Ultrasonography

●Ultrasonography may show the presence or absence of retinal detachment in eyes with opaque media e.g. vitreous hemorrhage, may show the location of retinal tears, and may show the cause of exudative retinal detachment, e.g. neoplasms, choroidal effusions, scleritis.

●Doppler ultrasound may demonstrate retinal blood flow and be used to differentiate a retinal detachment from an incomplete vitreous detachment in vitreous hemorrhage.

Optical coherence tomography (OCT)

●OCT may differentiate a retinal detachment from a retinoschisis, but only if the lesion is fairly central (30º).

Fluorescein angiography

●This may be useful in eyes with suspected exudative detachments to identify leakage from the choroidal or retinal vasculature, and may show retinal or macular ischemia in eyes with traction detachments due to proliferative retinopathy or occlusive vascular disease.

●Macular ischemia carries a poor prognosis for the return of central visual function.

Electrophysiology

●The absence of a recordable response electroretinogram ERG to bright-flash stimulation may indicate severe occlusive retinal vascular disease or extensive retinal detachment, and implies a poor prognosis.

●A normal electroretinogram and absent visually evoked response suggest a lesion in the optic pathway (most often, the optic nerve).

Associations

Rhegmatogenous retinal detachment

●Accommodation spasm, including miotics.

●Myopia.

●Lattice degeneration.

●Cystic retinal tufts.

●Acute posterior vitreous detachment.

●Retinoschisis (senile or congenital X-linked).

●Trauma (surgical and nonsurgical).

●Marfan syndrome.

●Stickler syndrome.

339 CHAPTERDetachment Retinal •

Retina • 30 SECTION

●Wagner syndrome.

●Viral retinitis (acute retinal necrosis and cytomegalovirus retinitis).

Traction retinal detachment

●Proliferative diabetic retinopathy.

●Proliferative vitreoretinopathy.

●Hypertensive retinopathy.

●Sickle cell retinopathy.

●Retinopathy of prematurity.

●Penetrating trauma.

●Retinal vascular occlusive disease.

Exudative retinal detachment

●Choroidal malignant melanoma.

●Choroidal hemangioma.

●Choroidal metastasis.

●Retinoblastoma.

●Toxocariasis.

●Vogt–Koyanagi–Harada syndrome.

●Central serous chorioretinopathy.

●Posterior scleritis.

●Sympathetic ophthalmia.

●Coats disease.

●von Hippel–Lindau syndrome.

●Eales disease.

●Optic nerve pit.

●Morning glory syndrome.

●Familial exudative vitreo-retinopathy (FEVR).

PROPHYLAXIS

Rhegmatogenous retinal detachment

●Eyes with a previous posterior vitreous detachment have a lower risk of rhegmatogenous detachment than eyes without a posterior vitreous detachment, regardless of other risk factors.

●Patients should be educated to seek ophthalmologic attention within 24 hours if the symptoms of an acute posterior vitreous detachment occur.

●Prophylactic treatment usually involves creating a chorioretinal scar around the margins of a retinal break or subclinical small detachment to prevent the ingress of fluid into the subretinal space.

●A chorioretinal adhesion is most commonly created using laser photocoagulation delivered through a slit lamp or an indirect ophthalmoscope.

●Transconjunctival and transscleral cryotherapy are equally efficacious; occasionally, both laser therapy and cryotherapy are useful in the same eye. Cryotherapy is often useful if the retinal view is impeded by hemorrhage or cataract.

●Retinal breaks may be classified as ‘asymptomatic’ if found on routine examination or ‘symptomatic’ if detected when accompanied by symptoms.

●In addition to the presence of symptoms, risk factors such as aphakia or pseudophakia, myopia, family history of retinal detachment or retinal detachment in the fellow eye influence the decision to offer prophylactic treatment to a retinal lesion.

●Symptomatic acute retinal tears (horseshoe or u-tears) or dialyses are almost always treated prophylactically.

●Symptomatic eyes manifesting lattice degeneration with atrophic holes are now believed not to require prophylactic

treatment, but may be followed depending on co-existing risk factors.

●Asymptomatic subclinical detachments are treated if there is a tear with persistent vitreoretinal traction or if the detachment extends posterior to the equator.

●Fellow eyes of patients with a prior rhegmatogenous detachment are considered for prophylactic treatment of lattice degeneration, asymptomatic breaks, subclinical detachments, and cystic retinal tufts particularly if the lesion is in the mirror-image position of the primary retinal break in the opposite eye with the retinal detachment.

●Fellow eyes of patients with non-traumatic giant retinal tears usually receive scatter or confluent peripheral panretinal photocoagulation.

Traction retinal detachment

●Prophylaxis depends on the underlying cause of traction detachment.

●Patients with proliferative diabetic retinopathy should undergo full panretinal laser photocoagulation.

●Patients with non-diabetic proliferative retinopathy, such as from a vascular occlusion or hypertensive retinopathy, should be considered for scatter laser photocoagulation treatment.

●The incidence of proliferative vitreoretinopathy may be reduced using anti-metabolite treatment at the time of vitrectomy surgery.

Exudative retinal detachment

●Prevention of exudative detachment usually involves appropriate identification and treatment of the underlying cause.

TREATMENT

Rhegmatogenous retinal detachment

●The main principles guiding the treatment of rhegmatogenous retinal detachments include identification and closure of the all retinal breaks by laser or cryo retinopexy, with internal or external tamponade, and relief of residual vitreoretinal traction. Subretinal fluid may be drained at the time of surgery or be allowed to be absorbed passively by the retinal pigment epithelium.

●The decision regarding the optimal treatment approach is dependent on multiple variables and must be made by the surgeon after a thorough discussion with the patient.

Pneumatic retinopexy

●This may be used as a primary outpatient office procedure for rhegmatogenous detachments with retinal breaks in the superior 3 clock-hours.

●Contraindications include lattice degeneration extending more than 3 clock-hours, active severe uveitis, significant vitreoretinal adhesions, inferior breaks with subretinal fluid, proliferative vitreoretinopathy worse than grade C2, and media opacities precluding adequate visualization of the entire fundus.

●Relative contraindications include pseudophakic eyes and eyes with advanced glaucoma.

●Excellent patient compliance with postoperative positioning is required.

●Anterior chamber paracentesis usually is performed initially.

●A gas bubble is injected through the pars plana into the midvitreous cavity with a 27or 30-gauge 0.5-inch needle.

●0.3 mL of air or perflurocarbon gases SF6, C2F6, or C3F8 (100% concentration) depending on the size of the eye, the degree of vitreoretinal traction, and the size, location, and number of retinal breaks.

●It is critical to verify that the central retinal artery is perfused and light perception vision has returned after gas injection.

●If the central retinal artery is not patent within 1 minute, repeat the aqueous paracentesis.

●Cryotherapy may be applied to the area surrounding the retinal break or breaks just before the gas injection.

●Alternatively, cryotherapy or laser photocoagulation may be used to create a chorioretinal adhesion 1 or 2 days after gas injection.

●In addition to treating the retinal breaks, scatter panretinal laser photocoagulation may be performed once the retina has reattached.

●Approximately 80% of all primary retinal detachments meet the criteria for pneumatic retinopexy.

●The overall anatomic success rate is approximately 70%.

●The complications of pneumatic retinopexy include new or missed retinal breaks, increased intraocular pressure, vitreous hemorrhage, subretinal gas, gas in the anterior hyaloid space, subconjunctival gas, cataract, vitreous incarceration, endophthalmitis, proliferative vitreoretinopathy, delayed reabsorption of subretinal fluid, cystoid macular edema, and extension of the detachment into the macula.

Scleral buckling

●This may require local or general anesthesia.

●It involves dissection of the conjunctiva and Tenon’s capsule to expose sclera.

●All retinal breaks must be localized and marked.

●Cryotherapy is applied to surround all breaks.

●The scleral explant is sutured to the sclera over each break.

●Patency of the central retinal artery is ensured after the buckle sutures are tied.

●Buckling material may be oriented radially or circumferentially.

●Radial buckles are used for large horseshoe tears to minimize fishmouth phenomenon or for posterior retinal breaks.

●A circumferential buckle may be segmental or encircle the globe. Encircling buckles create permanent indents but segmental ones tend to fade after 3 months.

●A segmental circumferential buckle is used for localized detachments with small breaks, localized detachments without identifiable breaks, detachments with minimal subretinal fluid, detachments of any size if the breaks are clustered within 2 clock-hours, retinal dialysis, or eyes with glaucoma (to preserve the conjunctiva for possible filtering surgery).

●Encircling circumferential buckles are relatively indicated

in aphakic or pseudophakic eyes, with multiple breaks in multiple quadrants, for vitreoretinal pathology (e.g. lattice degeneration) in multiple quadrants, for extensive detachment without an identifiable break, for high myopia, or for the presence of significant proliferative vitreoretinopathy.

●External drainage of subretinal fluid is not necessary in 90% of cases.

●Occasionally, an intravitreal gas bubble may be injected to tamponade the retinal breaks internally.

●The overall anatomic success rate is approximately 90%.

●The complications of scleral buckling include scleral rupture or perforation, choroidal or retinal perforation, cystoid macular edema, vitreous hemorrhage, subretinal hemorrhage, serous or hemorrhagic choroidal detachment, retinal incarceration in the drainage site, exposure or infection of the buckle, intrusion of the buckle, endophthalmitis, anterior segment ischemia, persistent subretinal fluid, proliferative vitreoretinopathy, change in refractive error, and strabismus.

Pars plana vitrectomy

●Vitrectomy is indicated in an increasing proportion of retinal detachments including patients with giant retinal tears, unusual or multiple large breaks, posterior breaks or macular holes, coexisting vitreous hemorrhage or other significant media opacities, pseudophakic or aphakic eyes, and proliferative vitreoretinopathy requiring membrane peel.

●Most surgeons use a three-port system in which sclerotomy incisions are made through the pars plana 3.0 to 4.0 mm posterior to the limbus.

●The inferotemporal sclerotomy is usually used for an infusion line, and the two superior sclerotomies are used for hand-held instruments and light sources.

●The vitreous is resected to the level of the vitreous base for 360º, with special attention paid to the meticulous removal of vitreous attached to the edges of all breaks and visible areas of abnormally firm vitreoretinal adhesion.

●Transcleral cryotherapy may be applied to the retinal breaks before drainage of shallow subretinal fluid.

●Alternatively, transcleral cryotherapy or laser treatment with an endoscopic probe or the indirect ophthalmoscopic delivery system can be performed after complete drainage of the subretinal fluid.

●Subretinal fluid is drained internally during a simultaneous air-fluid exchange through a preexisting retinal break or by creating a posterior drainage retinotomy (preferably in the superonasal quadrant). An external transcleral drain is also possible.

●Air is then exchanged for either gas SF6, C2F6, or C3F8 or silicone oil to provide internal tamponade of the retina whilst chorioretinal adhesion forms at the retinopexy.

●Heavy perfluorocarbon liquids may be a useful surgical adjunct during vitrectomy, especially for unrolling the flap of a giant retinal tear, in cases with a co-existing retinal traction detachment, for flattening detachments associated with posterior breaks, or for searching for small breaks not identifiable on initial internal search.

●Heavy silicone oil may provide inferior tamponade and may be left in the eye indefinitely if necessary.

●A scleral explant may be used in conjunction with vitrectomy.

●The anatomic success rate is approximately 90% after one operation.

●Complications of vitrectomy include cataract, transiently increased intraocular pressure, vitreous hemorrhage, subretinal hemorrhage, subretinal air or gas, subretinal perfluorocarbon liquid, retained perfluorocarbon liquid, endophthalmitis, failure of retinal reattachment, iatrogenic retinal breaks, proliferative vitreoretinopathy, macular pucker, cystoid macular edema, and serous or hemorrhagic choroidal detachment.

339 CHAPTERDetachment Retinal •

Retina • 30 SECTION

340 RETINAL VENOUS

OBSTRUCTION 362.30

Thomas K. Schlesinger, MD, PhD

Portland, Oregon

Christina J. Flaxel, MD

Portland, Oregon

Retinal vein occlusion is the second most frequent retinovascular disorder encountered in clinical practice.

ETIOLOGY

This entity occurs when there is an occlusion at the level of either the branch or central retinal venous system, causing a reduction in venous return. Patients typically present with acute, painless visual loss and should be followed for the development of retinal or iris neovascularization or macular edema.

Retinal arteries and veins, when adjacent, share an adventitial sheath. It is believed that chronic hypertension produces increasing thickness of the muscular arterial walls, leading to compression of the adjacent vein, creating turbulence. This results in the formation of a thrombus, located at the lamina in ischemic central retinal vein occlusion (CRVO) and at an arteriovenous crossing in branch retinal vein occlusion (BRVO). Other possible causes for retinal vein occlusion include hypercoagulable states, diabetes mellitus, chronic open-angle glaucoma, and prothrombotic states.

COURSE/PROGNOSIS

CRVO can be clinically classified as ischemic or nonischemic. Although 30% of non-ischemic CRVO cases progress to ischemic CRVO within 3 years, this clinical classification has important prognostic implications because nonischemic CRVO has a much more benign course. Visual loss in nonischemic CRVO is variable, with macular edema the major cause of reduced vision. Ischemic CRVO may lead to profound visual loss from macular edema or ischemia, hemorrhage, or neovascular glaucoma.

BRVO has a variable visual prognosis. Poor vision can be due to macular edema or ischemia, vitreous hemorrhage associated with posterior segment neovascularization, or epiretinal membrane.

DIAGNOSIS

Clinical signs and symptoms

Patients typically present with visual loss or metamorphopsia, although BRVO may be asymptomatic if it does not involve the macula. The presence of numerous ‘flame-shaped’ intraretinal hemorrhages is the hallmark of the disease. Nerve fiber layer infarcts are common, and these together with the hemorrhages give the classic ‘blood and thunder’ appearance of an acute CRVO. Retinal veins may be dilated and tortuous, and there may be evidence of disk swelling or macular edema. Clinical classification of this entity is made on the basis of the distribution of the retinal hemorrhages. CRVO involves all four quadrants, while BRVO is segmental. Neovascularization of the

retina or disk may occur in BRVO. Posterior segment neovascularization is uncommon in CRVO, but neovascularization of the iris or angle often complicates ischemic CRVO.

Laboratory findings

Fluorescein angiography may be useful in distinguishing nonischemic from ischemic vein occlusion, documenting the presence of macular edema, or demonstrating macular ischemia. Nonischemic CRVO is defined as having less than 10 disk diameters of capillary non-perfusion, while nonischemic BRVO has less than 5. Furthermore, this modality can be used to confirm the presence of retinal, disk, or iris neovascularization.

Optical coherence tomography (OCT) has emerged as a powerful test to assess macular edema, its progression or regression, and its response to treatment.

Differential diagnosis

●Ocular ischemic syndrome.

●Diabetic retinopathy.

●Vasculitis.

TREATMENT

Although anticoagulation, surgical adventitial sheathotomy (BRVO), radial optic neurotomy (CRVO), and creation of a chorioretinal anastomosis have been suggested to treat selected cases, no therapy for reversing a retinal vein occlusion has been proved beneficial by a controlled study. Intravitreal injection of triamcinolone acetonide for macular edema has become popular, numerous cases and series have been reported, but controlled trials are lacking. Some evidence suggests intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors may stabilize or improve visual acuity in selected CRVO cases.

Laser therapy has been proved beneficial for treating complications arising from retinal vein occlusion.

Central vein occlusion study

●Multicenter, randomized clinical trial that demonstrated panretinal laser photocoagulation caused regression of iris or angle neovascularization.

●Failed to demonstrate a beneficial effect of grid laser therapy for the treatment of macular edema in patients with CRVO.

Branch retinal vein study

●Multicenter randomized clinical trial that demonstrated the benefit of grid laser treatment for persistent macular edema in patients with worse than 20/40 vision.

●Demonstrated the efficacy of sectoral scatter laser photocoagulation for proliferative retinopathy associated with BRVO.

Laser photocoagulation guidelines

Branch retinal vein occlusion

●Persistent macular edema:

●A fluorescein angiogram is obtained to confirm macular edema. There should be significant clearing of hemorrhage to adequately assess macular edema.

●Treatment is offered to patients with macular edema without significant loss of macular perfusion, who have worse than 20/40 vision and who have had sufficient

340ObstructionCHAPTERVenous Retinal •

Retina • 30 SECTION

341 CHAPTERPigmentosa Retinitis •

Retina • 30 SECTION