Manual of Ocular Diagnosis and Therapy
6th Edition

8
Retina and Vitreous
Peter Reed Pavan
Andrew F. Burrows
Deborah Pavan-Langston
I. Normal anatomy and physiology
(see frontispiece)
  • The retina is the innermost layer of the eye and is derived from neuroectoderm. It is composed of two layers: the outer retinal pigment epithelium (RPE) and the inner neural retina, with a potential space between the two layers. The RPE, a single layer of hexagonal cells, is continuous with the pigment epithelium of the pars plana and ciliary body at the ora serrata. The inner sensory retina is a delicate sheet of transparent tissue varying in thickness from 0.4 mm near the optic nerve to approximately 0.15 mm anteriorly at the ora serrata. The center of the macula contains the thin sloping fovea that lies 3 mm temporal to the temporal margin of the optic nerve. The macula is close to the insertion of the inferior oblique muscle and is made almost entirely of cones. It is the site of detailed fine central vision (20/20 normal). Visual acuity decreases rapidly in the paramacular areas and is only 20/400 at a distance of 2 or 3 mm from the fovea. The ora serrata is located 6 mm posterior to the corneoscleral limbus nasally and 7 mm temporally. The scleral insertions of the medial rectus and the lateral rectus serve as landmarks for the location of the ora serrata nasally and temporally.
    Nutritional support for the sensory retina comes largely from the Müller cell, which spans almost the entire thickness of the retina. The inner two-thirds of the retina is nourished by the retinal vessels to the level of the outer plexiform layer. The outer one-third, consisting of the outer part of the outer plexiform layer, the photoreceptors and the RPE, is nourished by the choriocapillaris of the choroid.
  • Histology. The retina consists of 10 parts. Proceeding from the outside in, they are:
    • RPE.
    • Photoreceptor cells (rods and cones).
    • External limiting membrane.
    • Outer nuclear layer.
    • Outer plexiform layer.
    • Inner nuclear layer.
    • Inner plexiform layer.
    • Ganglion cell layer.
    • Nerve fiber layer.
    • Inner limiting membrane.
  • Physiology. The neuronal component of the retina consists of rods and cones that transduce light signals into electric impulses, which are amplified and integrated through circuitry involving bipolar, horizontal, amacrine, and ganglion cells and transmitted through the nerve fiber layer to the optic nerve.
  • Vitreous. The vitreous body, which makes up the largest volume of the eye, provides support for the delicate inner structures of the eye. It is limited by the lens anteriorly and by the ciliary body, pars plana, and the retina posteriorly. The vitreous is a clear jellylike substance consisting of a delicate framework of collagen interspersed with a hydrophilic mucopolysaccharide, hyaluronic acid. Delicate collagen fibrils attach the vitreous to the internal limiting membrane of the retina, the attachment being strongest around the ora serrata and at the optic disk and fovea.
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II. Tests of retinal function
  • Visual function is classified under the terms light sense, form sense, and color sense. Scientifically, these characteristics of incident light striking the eye are analyzed in terms of spatial, luminous, spectral, and temporal functions.
    • Visual acuity. In clinical practice, form sense is assessed by use of tests such as the Snellen chart test (see Chapter 1, Section II.B.). This test is primarily of macular function. It is subjective and depends on patient cooperation. Objective tests are of value in assessing visual acuity of infants, mentally disturbed patients, and malingerers. The amplitude of the visual evoked response (VER) or the optokinetic nystagmus response can be correlated with visual acuity. Thus, it is estimated that the visual acuity at birth is approximately 20/600 and improves by the age of 5 months to 20/60 and to adult levels by the age of 2 years.
    • Visual fields. Light sense is assessed by visual field examination, which reflects any damage to the visual pathway from the retina to the visual cortex. The conventional method of testing the visual field is called kinetic perimetry and consists of moving a target to identify points of equal retinal sensitivity. The normal visual field extends at least 90 degrees on the temporal side, 70 degrees nasally and inferiorly, and 60 degrees superiorly. Static perimetry involves the determination of the differential light threshold in chosen areas of the retina. This method is more sensitive and reproducible than kinetic perimetry (see Chapter 1, Section II.F. and Chapter 13, Section I.A–F.).
    • Color vision. The retinal cones mediate color vision. Many abnormalities of visual function are characterized by defects in color vision. The simplest and best-known method of testing color vision is by the use of Ishihara pseudoisochromatic plates. The Ishihara plates can only identify defects in red-green discrimination, whereas the American Optical Hardy-Rand-Ritter plates are useful in detecting red-green and blue-yellow defects. The Farnsworth-Munsell 100-hue test and anomaloscopes are more sophisticated devices used in clinical research on color vision testing (see Chapter 1, Section II.E.).
    • Dark adaptation. This test depends on the increase in visual sensitivity occurring in the eye when it goes from the light-adapted state to the dark-adapted state. The Goldmann-Weekers machine is used to plot the dark-adaptation curve. The eye to be tested is exposed to a bright light for 10 minutes and then all lights are extinguished. At intervals of 30 seconds, a measurement of light threshold is made in one area of the visual field by presenting a gradually increasing light stimulus until it is barely visible to the patient. The graph of decreasing retinal threshold against time shows an initial steep slope denoting cone adaptation and a subsequent gradual slope due to rod adaptation. Depression of the dark-adaptation curve occurs in conditions affecting the outer retina and RPE, such as retinitis pigmentosa.
    • Fluorescein angiography is the study of retinal and choroidal vasculature using fluorescein (see Chapter 1, Section III.G.).
      • Technique. Fluorescence is a physical property of certain substances that, on exposure to light of short wavelength, emit light of longer wavelength in a characteristic spectral range. Sodium fluorescein, a yellow-red substance, absorbs light between 485 and 500 nm in aqueous solution and exhibits a maximum emission between 525 and 530 nm. A 5-mL bolus of dye is rapidly injected via the antecubital vein, and rapid retinal photographs are taken with a fundus camera containing an excitatory filter with maximum transmission between 485 and 500 nm and a barrier filter peaking close to the maximum of the fluorescein emission curve (between 525 and 530 nm). The value of fluorescein angiography is based on the fact that fluorescein dye does not penetrate healthy RPE and normal retinal capillaries because of the tight endothelial junction. Fluorescein does leak freely from the normal choriocapillaris. Under optimum conditions, the smallest retinal capillaries (5 to 10 μm in diameter) can be seen with this technique, a feat impossible by ophthalmoscopy or by color photography.
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      • Use in retinal and choroidal disease. Fluorescein angiography is of particular value in elucidating small vessel disease such as diabetic retinopathy, outlining clearly such changes as microaneurysms, shunt vessels, and sites of early neovascularization. Vascular abnormalities within the retina commonly leak fluorescein because of damage to the endothelium. New vessels, both those anterior to the retina and those arising from the choroid under the retina, characteristically leak fluorescein because of the absence of tight endothelial junctions. Angiography provides a valuable means of identifying such vessels in macular degeneration, diabetes, sickle cell disease, and retinal vein obstruction. It also provides a means of assessing the efficacy of treatment, particularly photocoagulation, in eliminating these vessels and in sealing leaks from vascular abnormalities within the retina, as in clinically significant diabetic macular edema (ME).
      • Use in RPE and optic nerve evaluation. Although angiography does not provide any clue regarding the function of RPE, it anatomically delineates the true extent of RPE atrophy in diseases affecting RPE, such as rubella, retinitis pigmentosa, and age-related macular degeneration. Angiography is also helpful in distinguishing early papilledema, in which both the superficial and deep vascular networks become dilated and leak fluorescein, from “full” disks or disks with buried drusen. Papillitis shows many of the fluorescein characteristics of early papilledema. In optic atrophy, a loss of vessels occurs in both the superficial and the deep networks.
    • Optical coherence tomography (OCT) measures tissue variation in light interference patterns to construct a 2-D cross-sectional image of the retina. The relative position of features such as hyaloid face, internal limiting membrane, RPE, and intraretinal and subretinal fluid collections are well defined.
    • Electrophysiology. There are three major electrophysiologic tests used in the investigation of the visual system (see also Chapter 1).
      • Electro-oculography (EOG) measures slow changes in the standing potential of the retina caused by the interaction of the RPE with the photoreceptors. Electrodes are attached to the skin over the orbital margin opposite the medial and lateral canthi, and the potential difference between the electrodes is amplified and recorded after both light and dark adaptation as the patient is asked to look back and forth at targets to the right and left. The maximum height of the potential in light divided by the minimum height of the potential in dark gives the Arden ratio, which is normally 1.85 or greater. Its principal diagnostic usefulness is in distinguishing Best vitelliform degeneration (in which the ratio is abnormal but the electroretinography [ERG] is normal) from other macular diseases such as Stargardt disease or pattern dystrophies.
      • ERG reflects the chain of graded electric responses from each layer of the retina. The human response, for clinically useful purposes, is a biphasic wave, an early negative a wave, generated by the rods and cones, followed by a larger positive b wave, generated in the Müller and the bipolar cell layer. The recording is done with a corneal contact lens electrode and a reference electrode on the forehead. Cone responses predominate under photoptic testing conditions when a bright flash stimulates the retina. Rod responses predominate in a scotopic environment when a dim flash is used. A bright flash under scotopic conditions elicits a combined response. In addition, the ERG can distinguish the differences in response between the rods and cones to flickering flash; only the cones respond at 30 Hz because they have a much higher temporal resolution than the rods. The ERG is very useful in evaluating early retinal function loss before ophthalmoscopic changes are evident. The ERG is normal in diseases involving only the ganglion cells and the higher visual pathway, such as optic atrophy.
      • Visual evoked response (VER). The VER is the response of the electroencephalogram recorded at the occipital pole and is a macula-dominated response due to the disproportionately large projection of the macular retina in the occipital cortex. The VER can be recorded using an intense flash
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        stimulation or a pattern stimulation. The VER is the only clinically objective technique available to assess the functional state of the visual system beyond the retinal ganglion cells. The flash VER can assess retinocortical function in infants and demented or aphasic patients, and it can distinguish patients with psychological blindness from those who have an organic basis for poor vision.
III. Retinal vascular disease
  • Retinal vascular anomalies cause loss of visual function primarily through incompetence of the endothelial lining of the anomalous vessels, permitting transudation of serum and, less often, blood into the retinal tissues and the subretinal space. The serous component of the exudate is resorbed, leaving behind clinically visible bright yellow deposits with sharp borders called hard exudates, often in the macular area. The presence of such deposits in the absence of leakage in the posterior pole on fluorescein angiography should lead to a search of the peripheral retina for a vascular anomaly. Effective methods of treatment of these lesions include photocoagulation and cryotherapy, with repeated freezing and slow thawing. Photocoagulation can be effective even after serous detachment of the retina has occurred. Once the lesion is destroyed, the subretinal fluid will absorb. Retinal vascular anomalies may be classified as follows:
    • Retinal telangiectasia or Coats disease. The basic lesion in Coats disease is a congenital anomaly of the vasculature of the retina, manifested ophthalmoscopically as telangiectasias. There is a marked male predominance (85%) and more rapid progression in children under 4 years of age, simulating retinoblastoma. Fluorescein angiography shows an abnormally coarse net of dilated capillaries, often with irregular aneurysmal dilations, which leak fluorescein. The telangiectasis may involve superficial or deep retinal vessels and can be associated with hemorrhages and hard exudates. Even advanced cases may regress spontaneously. Retinal telangiectasia is usually unilateral. Patients with loss of central vision from subretinal or intraretinal exudation are ideal candidates for photocoagulation. There is a high incidence of recurrence after treatment; therefore, these patients should be followed indefinitely.
    • Retinal angiomatosis or von Hippel-Lindau disease. The basic lesion in the phakomatosis, von Hippel-Lindau disease, is a vascular hamartoma consisting of capillaries with proliferating endothelial cells, a feeding artery, and draining veins. This disease is bilateral in 50% of patients. It can occur spontaneously or be dominantly inherited. Partly through abnormal hemodynamics and partly through hypertrophy and hyperplasia of the constituent elements, these lesions may enlarge over a period of time. However peripheral the lesion may be, abnormal permeability can result in changes at the macular region, including development of hard exudates, retinal edema, and serous detachment. Repeated photocoagulation of the tumor will usually eliminate the exudation. Long-term follow-up is needed to detect new lesions. Treatment of angiomas on or near the temporal margin of the optic nerve head is difficult without destroying central vision. Appropriate systemic evaluation is necessary to detect associated central nervous system vascular abnormalities (hemangioblastomas), renal cell carcinoma, and pheochromocytoma.
    • Retinal cavernous hemangioma may arise in the retina or optic nerve head. The lesion is composed of clusters of saccular aneurysms filled with dark venous blood. Fluorescein angiography shows that these lesions do not leak and that they have a sluggish blood flow. Dermal vascular lesions and intracranial lesions may be associated with this condition. Photocoagulation may be used when spontaneous hemorrhage occurs.
    • Arteriovenous (AV) malformations, a rare condition, have been called “racemose” or “cirsoid” angioma. There is a direct communication between the artery and vein with no intervening capillary bed. The retinal vessels appear dilated and tortuous. Smaller caliber malformations are well compensated, stationary, and usually do not require any treatment. Large-caliber AV malformations can have
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      a breakdown of the blood-retinal barrier with development of ME. Photocoagulation may be of benefit in these cases. Severe cases of widespread AV malformations, often with face, orbit, and intracranial associations, are not amenable to therapy because of widespread retinal disorganization (i.e., Wyburn-Mason syndrome).
    • Retinal macroaneurysms occur in the retinal arterioles of arteriosclerotic and often hypertensive elderly patients. The aneurysms appear as outpouchings of the arteriolar wall that leak on fluorescein angiography. They can bleed into the vitreal, retinal, subretinal, or subretinal pigment epithelial spaces. The blood will often resorb, and there will be no further hemorrhaging. The artery beyond the aneurysm may become sclerosed and occluded. If ME or exudate formation is present, gentle photocoagulation of the aneurysm without occluding the associated arteriole may help.
  • Vascular retinopathies
    • Mechanisms of visual loss. These diseases reduce vision through either abnormal vascular permeability or retinal ischemia. The former decreases vision principally through exudation of fluid into the macula. Clinically, exudation is seen as thickening of the retina, cystic changes in the retina, and/or as hard exudates. On fluorescein angiography, the leakage can be diffuse or specific, such as that coming from a microaneurysm.
      Areas of retinal ischemia often show no changes on ophthalmoscopy. On fluorescein angiography, ischemia appears as focal or diffuse areas of capillary disappearance, often called capillary dropout. Sometimes an area of apparent capillary dropout on fluorescein angiography may correlate with areas of retinal whitening about one-quarter of a disk diameter in size. Because of their fuzzy or ill-defined edges, these lesions are sometimes called soft exudates. This feature plus their bright white appearance has also earned them the eponym cotton-wool spots (CWS) (see Section III.B.8.a). Retinal ischemia may also correlate with widespread retinal whitening as seen in acute central retinal artery occlusion.
      Ischemia can cause visual loss in a variety of ways. Ischemic areas can contribute to leakage in the macula. The perifoveal capillary network may be partially or totally destroyed. Vascular endothelial growth factor (VEGF) released by partially ischemic tissue may induce the proliferation of new vessels on the disk or surface of the retina. These new vessels become tightly bound to the posterior vitreous. They leak fluid into it, and this fluid induces contraction of the vitreous gel, resulting in traction on the new vessels, which can then bleed into the vitreous cavity. Depending on the size of the hemorrhage, only a few floaters might be seen, or there can be a sudden and severe decrease in vision. The blood components can cause further contraction of the vitreous and further bleeding, setting up a vicious cycle of recurrent hemorrhaging. In addition to, or instead of, inducing vitreous hemorrhaging, the traction can lead to pulling and detachment of the retina under and around the new vessels (traction retinal detachment). If the fovea is involved, vision will decrease. Retinal ischemia may also induce new vessel formation on the iris and trabecular meshwork blocking Schlemm’s canal, leading to severe pressure elevations (neovascular glaucoma). In diabetic retinopathy, posterior proliferative changes predominate with vitreous hemorrhaging and traction retinal detachments, whereas in central retinal vein occlusion, neovascular glaucoma is more common. In artery occlusions, total ischemia with destruction of the perifoveal capillary network is the mechanism of visual loss. New vessel formation either anteriorly or posteriorly is rare, presumably because little VEGF is produced by totally ischemic tissue.
    • Management of the vascular retinopathies consists of treatment of the underlying medical condition. Depending on the underlying cause, laser photocoagulation has been shown in controlled clinical trials to be of visual benefit in treating the exudation of fluid into the macula and the retinal complications of the partial ischemia by reducing or eliminating new vessel growth. Intravitreal triamcinolone acetonide (Kenalog) (4 mg in 0.1 mL) or bevacizumab (Avastin (1.25 mg
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      in 0.05 mL) have shown promise in uncontrolled case series in the treatment of macula edema. Intravitreal bevacizumab has anecdotally been shown to cause regression of new vessels, both on the disc and retina and anteriorly on the iris and trabecular meshwork. Pars plana vitrectomy is useful in managing vitreous hemorrhages and traction retinal detachments.
    • Hypertensive retinopathy. The retinal changes in hypertension are essentially the same as in the retinopathies seen in the collagen diseases and are secondary to local ischemia.
      • Pathology. Essential hypertension is associated with thickening of the arteriolar wall caused by intimal hyalinization and hypertrophy of muscle fibers in the media. Sustained elevations of blood pressure cause necrosis of vascular smooth muscle and seepage of plasma into the unsupported wall through a damaged endothelium. Angiography at this stage will demonstrate a focal leak of fluorescein. Progressive plasma exudation into the vessel wall with further muscle necrosis results in secondary occlusion and the typical picture of advanced fibrinoid necrosis.
      • Clinical findings
        • Retinal. In its milder forms, hypertension causes increased arteriolar light reflexes called “copper and silver wiring.” Thickening of the common adventitial sheath compresses venules where they pass under the arterioles and causes arteriovenous (AV) nicking. In its extreme form, this compression can cause a branch retinal vein occlusion (BRVO) (see Section III.B.4.a). With higher levels of blood pressure, intraretinal hemorrhages (typically flame shaped, indicating they are in the nerve fiber layer), CWS, and/or retinal edema are seen. Malignant hypertension is characterized by papilledema, and with time, a macular star figure.
        • Choroidal. Young patients with acute, severe elevations in blood pressure from pheochromocytoma, preeclampsia, eclampsia, or accelerated hypertension can develop hypertensive choroidopathy. Pale or reddish areas of RPE (Elschnig spots) indicate poor choroidal perfusion. Focal serous or large exudative retinal detachments occur in more severe disease.
      • Prognosis. Serious impairment of vision does not usually occur as a direct result of the hypertensive process unless there is local arteriolar or venous occlusion. Patients with hemorrhages, CWSs, and edema without papilledema have a mean life expectancy of 27.6 months. With papilledema, life expectancy is 10.5 months.
    • Venous retinopathy. Retinal vein occlusion can manifest itself as a central retinal vein occlusion (CRVO), in which the site of occlusion is behind the cribriform plate, or as a branch retinal vein occlusion (BRVO), in which the occlusion is anterior to the cribriform plate. Obstruction of outflow occurs in retinal vein occlusion, resulting in an increase of intravascular pressure and stagnation of flow. The increase in intravascular pressure is responsible for abnormal leakage, edema, and hemorrhage. Collaterals often form over several weeks to months. In CRVO, the collaterals are on the disc between the retinal and choroidal circulations. In BRVO, the collaterals are within the retina between areas affected and those unaffected by the BRVO. Stagnation of flow can also lead to ischemia of endothelial cells resulting in varying degrees of capillary nonperfusion and CWS formation. The development of large areas of capillary closure stimulates the growth of new vessels. In BRVO, these new vessels are usually at the junction of the normal and ischemic retina. They can lead to vitreous hemorrhage. In CRVO, the new vessels commonly occur on the iris and trabecular meshwork and cause neovascular glaucoma. They also occur on the disc or retina.
      • BRVO
        • The site of occlusion in BRVO is usually at AV crossings. Thickening of the arteriolar wall within the common adventitial sheath around the two vessels compresses the venule and induces thrombosis. When a BRVO is not at an AV crossing, vasculitis should be suspected.
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        • Conditions predisposing to BRVO are systemic arterial hypertension, cardiovascular disease, increased body mass index at age 20 years, and glaucoma. The superotemporal quadrant is affected more than 60% of the time. The clinical picture consists of superficial and deep intraretinal hemorrhages with a variable number of CWSs. Subhyaloid and vitreous hemorrhages occur rarely.
        • The natural history of BRVO varies from complete resolution with no long-term visual difficulties to severe visual loss. Patients presenting acutely should be followed for at least 3 months to allow for the development of collaterals and spontaneous improvement. In general, about 55% of patients retain vision of 20/40 or more after 1 year. In those who do not, the most common causes are ME and preretinal neovascularization. ME occurs in 57% of cases with temporal branch occlusion. The Branch Vein Occlusion Study showed that photocoagulation was effective treatment of ME in patients who had had a BRVO for at least 3 months, acuity 20/40 or worse, and an intact perifoveal capillary network. This same study showed that panretinal photocoagulation in the distribution of the occluded vein significantly lessened the chance of a vitreous hemorrhage in eyes that developed retinal or disc neovascularization. For macular disease, a light grid pattern of 100- to 200-μm spots is given to areas of leakage identified by fluorescein in the macular region extending no closer to the fovea than the edge of the foveal avascular zone and not extending peripheral to the major vascular arcade. Areas of dense intraretinal hemorrhage are avoided. There is no effective treatment for visual loss secondary to macular ischemia.
      • CRVO
        • Clinical course. CRVO presents a wide spectrum of clinical appearances. The variations depend on the severity of obstruction of venous outflow. In the mildest cases, minimum dilation of veins and hemorrhages are present with little ME and little decrease in vision. In the severe cases, vision may deteriorate to hand motions, with extensive deep and superficial hemorrhages with stagnant blood columns in grossly dilated veins and numerous CWSs throughout the fundus. Mild to severe disk edema may be present. As in BRVO, the principal vascular response in CRVO consists of dilation of retinal capillaries, abnormal vascular permeability, and retinal capillary closure. Macular edema is often present in the nonischemic CRVO with dilated, leaking capillaries. Ischemic CRVO is characterized by widespread capillary closure as demonstrated on fluorescein angiography. Serious neovascular complications are common, such as rubeosis iridis and neovascular glaucoma. If it is going to occur, rubeosis iridis and/or neovascularization of the angle is usually visible within 6 months of the occlusion. The incidence of the latter complication depends upon the amount of retinal ischemia. In eyes with less than 10 disk areas of nonperfusion, less than 10% will develop rubeosis or angle neovascularization. In eyes with more than 80 disk areas of nonperfusion, approximately 50% will have rubeosis or angle neovascularization on follow-up.
        • Diseases predisposing to CRVO include cardiovascular disease, systemic hypertension, diabetes, and open-angle glaucoma. Increased physical activity lowers the chance of a CRVO, as does the use of estrogen in postmenopausal women.
        • Differential diagnosis. There are four conditions from which CRVO must be differentiated.
          • Venous stasis retinopathy or retinopathy of carotid occlusive disease has been described in patients with internal carotid stenosis or occlusion. Venous stasis retinopathy is characterized by micro-aneurysms in close proximity to the retinal veins and small blossom-shaped hemorrhages in the midperiphery, as well as dilation of the
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            retinal veins. Other signs of unilateral carotid occlusive disease include a larger appearance to the arterioles on the affected side.
          • Systemic hypertension often coexists with CRVO. Severe hypertensive retinopathy, however, is usually bilateral and often symmetric with superficial hemorrhages and a macular star of hard exudates present. Retinal hemorrhages do not extend to the periphery as in CRVO. Severe ME and visual loss are rare in hypertensive retinopathy.
          • Hyperviscosity syndromes, such as macroglobulinemia, leukemias, polycythemias, and some hyperlipemias, show a clinical picture similar to CRVO. These conditions are usually bilateral with few hemorrhages and little ME.
          • Diabetic retinopathy is usually bilateral. Beading and reduplication of the vein is rare in CRVO.
        • Treatment. Underlying medical conditions such as hypertension, elevated blood sugar, or congestive heart failure should be corrected. Increased intraocular pressure (IOP) in either the involved or uninvolved eye should be corrected. Focal photocoagulation for ME does not improve acuity. A careful undilated slitlamp examination and gonioscopy should be done every month for 6 months. If neovascularization is detected, give panretinal photocoagulation promptly to prevent neovascular glaucoma. Eyes presenting with good vision (>20/40) have a fair chance of retaining good vision. Eyes with poor vision are more likely to have widespread ischemia, are not likely to recover their vision, and have an increased incidence of rubeosis and angle neovascularization.
    • Diabetic retinopathy is the leading cause of new cases of blindness in the United States in patients between the ages of 20 and 74. In the developed Western countries, at least 12% of all blindness is due to diabetes. In the United States, a diabetic patient has more than a 20-fold chance of becoming blind compared to a nondiabetic counterpart.
      • Risk factors. The duration of insulin-dependent diabetes is the main factor in the appearance of diabetic retinopathy. When diabetes is diagnosed before age 30 years, the risk of developing retinopathy is about 2% per year. After 7 years and 25 years, 50% and 90% of diabetic patients, respectively, will have some form of retinopathy. After 25 to 50 years of diabetes, 26% will have the proliferative form. Puberty and pregnancy both stimulate development of retinopathy. The 10-year rate of vision loss to less than 20/40 bilaterally is about 10% in juvenile diabetics, 38% in adult-onset, insulin-dependent disease, and 24% in adult-onset, non-insulin-dependent diabetes. The Diabetes Control and Complications Trial (DCCT) showed that intensive insulin treatment to control blood sugar levels tightly decreased the risk of developing severe nonproliferative or proliferative retinopathy and reduced the need for laser surgery by about 50%.
      • Types of diabetes
        • Type I (juvenile onset) diabetes cases are autoimmune (pancreatic destruction) and have a high risk for developing severe proliferative retinopathy.
        • Type II (adult onset) cases have normal to high insulin production but insulin-resistant receptor cells. There are more type II patients with blinding sequelae because of the greater number of type II diabetic patients.
      • Medical evaluation. Every diabetic patient deserves the benefit of a comprehensive evaluation, with careful attention paid to determine the presence of symptoms of diabetic retinopathy, such as decreased vision, distortion of vision, loss of color vision, and the presence of floaters. The duration of diabetes and the method of control of diabetes should be assessed. The presence of associated systemic disease should be noted. Hypertension is present in 20% of insulin-dependent diabetics and in 58% of non-insulin-dependent
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        diabetics. Optimal medical control is key to minimizing ocular and systemic complications.
      • Clinical appearance. Diabetic retinopathy is classified into four groups.
        • Background retinopathy (nonproliferative retinopathy). The diabetic lesions of background retinopathy are dilated veins, intraretinal hemorrhages, microaneurysms, hard exudates, edema, and CWS. Dot-blot hemorrhages, retinal edema, and hard exudates result from increased vascular permeability. Microaneurysms cluster around areas of capillary nonperfusion.
        • Preproliferative diabetic retinopathy represents the most severe stage of background retinopathy (nonproliferative retinopathy). Preproliferative retinopathy is categorized by the presence of many intraretinal hemorrhages and microaneurysms, intraretinal microvascular abnormalities (dilated vessels within the retina), and venous beading. There is widespread capillary closure. Approximately 10% to 50% of patients with preproliferative retinopathy develop proliferative retinopathy within a year.
        • Proliferative diabetic retinopathy occurs in 5% of patients with diabetic retinopathy. In the proliferative stage, vascular abnormalities appear on the surface of the retina or within the vitreous cavity, starting postequatorially. Visual loss can be severe. New blood vessels grow on the surface of the retina and the optic nerve and are usually attached to the posterior hyaloid surface of the vitreous body. In the cicatricial stage, contraction of the vitreous body causes traction on the retinal neovascularization, resulting in vitreous hemorrhage and/or traction retinal detachment.
        • Diabetic maculopathy may result from increased vascular permeability with or without intraretinal lipoprotein deposits (hard exudates) or, less commonly, from ischemia due to closure of foveal capillaries. Diabetic maculopathy may be seen in any phase of retinopathy except for very early background disease.
      • Pathology. Histology of eyes with diabetic retinopathy shows loss of intramural pericytes and extensive capillary closure in trypsin-digest flat preparations of the retina. The blood-retinal barrier is compromised mainly by defects in the junctions between abnormal vascular endothelial cells. The most widely accepted working hypothesis for the pathogenesis of proliferative retinopathies such as diabetes, retinopathy of prematurity (ROP), and CRVO is that a retina rendered ischemic by widespread capillary closure elaborates VEGF, which stimulates retinal neovascularization and/or rubeosis of the iris and trabecular meshwork.
      • Management. Diabetic eyes should be inspected for rubeosis with a slitlamp before the pupil is dilated because fine vessels on the iris are almost impossible to see once mydriasis is induced. Gonioscopy is necessary if new vessels are seen on the surface of the iris with the slitlamp. To properly inspect the retina, wide pupillary dilation is needed. Diabetic retinas are best examined using a binocular viewing system that provides moderate magnification, such as a slitlamp at 10× in conjunction with a 90-D lens to allow the detection of retinal thickening and tractional retinal detachments with stereoscopic vision. It is important to have the patient look in various fields of gaze so the more peripheral retina to the equator can be inspected, because approximately 27% of retinal abnormalities are found outside the central 45-degree area. Indirect ophthalmoscopy provides a view of the retina at and anterior to the equator. Color photography is used to document the progress or regression of retinopathy following treatment. Fluorescein angiography defines areas of leakage and ischemia and confirms the presence of neovascularization of the retina or disc. OCT shows areas of retinal edema.
        • Three major clinical trials have been carried out by the National Eye Institute to determine the retinal history of nonproliferative and proliferative diabetic retinopathy, as well as guidelines for treatment.
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          • The Diabetic Retinopathy Study (DRS) showed that scatter argon laser photocoagulation (panretinal photocoagulation [PRP]) reduced the incidence of severe visual loss (vision less than or equal to 5/200) by half or more in eyes with neovascularization on the disc or within one disc diameter of the disk (new vessels disc, or NVD). A similar reduction in the rate of severe visual loss was obtained in eyes with neovascularization elsewhere (new vessels elsewhere or NVE) associated with vitreous hemorrhage.
          • The Early Treatment Diabetic Retinopathy Study showed that eyes with clinically significant macular edema benefited from focal argon laser to discrete areas of leakage and grid photocoagulation to areas of nonperfusion or diffuse leakage. Moderate visual loss was defined as a doubling of the visual angle (e.g., going from 20/20 to 20/40). Laser treatment reduced the risk of such visual loss by 50% or more, increased the chance of improved vision, and had only minor visual field effect. Focal photocoagulation for vision-threatening ME should be given before scatter photocoagulation (PRP) for approaching high-risk proliferative retinopathy. Aspirin had no clinical effect. Observation only was indicated for eyes with mild to moderate nonproliferative retinopathy.
          • The Diabetic Retinopathy Vitrectomy Study showed that type I diabetic patients with recent, severe vitreous hemorrhage associated with vision equal to or less than 5/200 undergoing early vitrectomy (within 6 months) had a notably better chance of attaining 20/40 or better vision than those whose vitrectomy was deferred a year. Type II or mixed diabetic patients did not benefit from early vitrectomy for severe vitreous hemorrhage. Patients with severe proliferative retinopathy with vision equal to or greater than 10/200 had a better chance of attaining 20/40 or better vision if they had early vitrectomy than those managed with conventional therapy.
        • Follow-up and management guidelines for diabetic retinopathy, as recommended by the American Academy of Ophthalmology, are as follows:
          • Normal or rare microaneurysms: annual examination, good diabetic control.
          • Mild nonproliferative diabetic retinopathy (NPDR) (few hemorrhages and microaneurysms in one field or several fields, but no ME or exudates): examination every 9 months, good diabetic control.
          • Moderate NPDR (hemorrhages and/or exudates in all fields, intraretinal microvascular abnormalities [IRMAs] or CWS): examination every 6 months, good diabetic control.
          • Severe NPDR (one or more of the following: severe number of retinal hemorrhages and microaneurysms, moderate IRMAs, venous beading): examination every 4 months.
          • ME at any time: examination every 3 to 4 months, focal laser if clinically significant edema develops.
        • Clinically significant ME includes any of the following features:
          • Thickening of the retina at or within 500 μm of the center of the macula.
          • Hard exudates at or within 500 μm of the center of the macula.
          • Zones of retinal thickening one disk area or larger, any part of which is within one disk diameter of the center of the macula.
            Appropriate argon laser photocoagulation reduces the risk of visual loss substantially.
        • Non-high-risk proliferative diabetic retinopathy occurs when there are any new vessels but the eye does not yet have high-risk characteristics (HRC) as defined by the DRS. These eyes should be followed
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          every 2 to 3 months. In patients with bilateral non-high-risk proliferative retinopathy, PRP should be considered in one eye.
        • Proliferative retinopathy with HRC. Panretinal laser photocoagulation is the treatment of choice for this stage, which is characterized by one or more of the following:
          • NVD greater than one fourth to one third of the disk area.
          • Vitreous or preretinal hemorrhage associated with less extensive NVD or NVE one-half disk area or more in size.
        • Laser applications. The risk of severe visual loss in patients with HRC is substantially reduced by means of panretinal laser photocoagulation. The goal is to achieve regression of existing vessels and inhibition of new vessel growth. Treatment is commonly done in two to four stages separated by 1 or more weeks. Typically, 400 to 600 burns of 500-μm diameter are placed in the retinal periphery in one session. They come to within 500 μm of the disk on the nasal side. To preserve central vision, none are placed within two disk diameters of the center of the macula. To preserve peripheral field, burns are placed one to one-half burn width apart. The duration of each burn is 0.1 to 0.2 seconds and the power is adjusted to achieve definite retinal whitening. Flat new vessels away from the disk receive confluent burns. Areas of significant fibrosis, traction retinal detachment, and vitreous or preretinal hemorrhage are avoided. If proliferative diabetic retinopathy continues to be active despite panretinal laser photocoagulation in all quadrants, additional laser spots may be added between, or anterior to, the old laser scars. Panretinal cryoablation is useful in selected patients. If a blinding vitreous hemorrhage occurs despite these measures or before laser can be given, pars plana vitrectomy should be performed within 6 months in type I diabetics. Intraoperative laser photocoagulation is often performed when these patients undergo pars plana vitrectomy. If B-scan ultrasonography suggests an underlying traction retinal detachment of the macula, vitrectomy should be done in all patients. Of course, when a recent traction macular detachment or a combination traction and rhegmatogenous retinal detachment is present even when there is no vitreous hemorrhage, vitreous surgery is indicated.
          PRP is not necessary in phakic eyes if there is peripupillary rubeosis but no abnormal new vessels on the trabecular meshwork. Such eyes should be followed every 3 months. If there are new vessels in the angle, the eye is aphakic, or the eye is pseudophakic with a broken posterior capsule, prompt PRP is needed to prevent neovascular glaucoma even when proliferative diabetic retinopathy with HRCs is absent.
          Focal macular laser therapy for clinically significant macular edema commonly uses 100- to 200-μm spot sizes and 0.1-second duration. The goal is to change the color of leaking microaneurysms through direct treatment; grid treatment is given to areas of diffuse leakage and ischemia. Leaks within 500 μm of the center of the macula are usually not treated with the laser unless previous treatment has failed, vision is less than 20/40, and treatment will not damage the perifoveal capillary network on the edge of the foveal avascular zone.
    • Sickle cell retinopathy. The mutant hemoglobins S and C are alleles of hemoglobin and cause sickle trait (HbAS), sickle cell disease (HbSS), and hemoglobin SC disease in 8%, 0.2%, and 0.2% of patients, respectively; most patients affected by these alleles are African American. Sickle cell thalassemia (S Thal), in which beta polypeptide chain synthesis is severely depressed as well as defective, is rare (0.03%). The initial event in the retinopathy is intravascular sickling, hemostasis, and thrombosis. Any hemoglobinopathy may cause nonproliferative or proliferative retinopathy, but severe proliferative disease is more common in HbSC and S Thal than HbSS, which causes more systemic complications. The incidence of significant visual loss is about 4%.
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      • Diagnosis is by positive “sickle prep” and hemoglobin electrophoresis, the only way to distinguish homozygous from heterozygous disease.
      • Nonproliferative sickle retinopathy is characterized by salmon patch hemorrhages occurring after peripheral retinal arteriolar occlusion; refractile spots, which are resorbed hemorrhages leaving hemosiderin deposition; and black sunburst lesions, which are areas of RPE hypertrophy and hyperplasia with posthemorrhage hemosiderin. Central retinal artery occlusion (CRAO) may also occur with or without retinopathy.
      • The five progressive stages of proliferative sickle cell retinopathy are
        • Peripheral arteriolar occlusion due to intravascular sickling.
        • Peripheral arteriovenous anastomosis.
        • Sea fan (retinal arterial) neovascularization, which is most frequent at about the equatorial plane superotemporally. Fluorescein angiography is valuable for detecting early sea fans.
        • Vitreous hemorrhage.
        • Retinal detachment, which usually begins in areas affected by fibrovascular proliferation and local vitreous traction.
      • Treatment. Application of low-energy scatter argon laser photocoagulation to the involved ischemic areas induces regression in neovascular fronds. Application of high-energy laser photocoagulation to close fronds is not recommended because of the high incidence of complications, such as hemorrhaging, choroidal ischemia, and neovascularization with vitreal extension and retinal detachment. Peripheral cryotherapy, causing mild retinal whitening of the nonperfused areas, is an alternative mode of therapy. Pars plana vitrectomy is useful in treating patients with vitreous hemorrhage. Special precautions should be taken if retinal detachment surgery is undertaken, because these eyes are prone to develop anterior segment ischemia. These measures include nasal oxygen, omission of vasoconstrictors such as epinephrine from local anesthetics, and avoidance of elevated IOP at all times. Sparing use of cryotherapy is preferable to extensive applications. Diathermy should be avoided. Muscles should not be detached. Subretinal fluid is drained where technically possible. A segmental scleral buckle is preferable to one with an encircling band. The rate of anterior segment ischemia is greatly reduced if vitrectomy is done in combination with, or instead of, a scleral buckle. This allows complete control of the IOP so the pressure spikes associated with conventional buckling are avoided and intraocular sickling is prevented. Epinephrine is omitted from the intraocular irrigating solutions. With vitrectomy, the partial exchange transfusions used in the past are usually not necessary.
    • Retinopathy of prematurity (ROP) (see Chapter 11, Section X.A.)
    • Other causes of ischemic retinopathies
      • CWS are seen in ischemic retinopathies as well as nonischemic retinopathies. They represent disruption of axoplasmic flow in the nerve fiber layer. They commonly fade over 2 to 3 months. Systemic etiologies should be searched for in any patients with CWS. Although diabetes, AIDS, and hypertension are the most frequent associated disorders, CWS also occur in collagen vascular diseases such as dermatomyositis, systemic lupus erythematosus, polyarteritis nodosa, and giant-cell arteritis. Other conditions where CWS are found include cardiac valvular disease, radiation retinopathy, carotid occlusive disease, pulseless disease, syphilis, leukemia, trauma, metastatic carcinoma, intravenous (i.v.) drug abuse, sarcoidosis, ulcerative colitis, hemoglobinopathies, interferon therapy, and Purtscher retinopathy. Local etiologies include epiretinal membranes, central and branch retinal vein occlusions, and retinal artery occlusions. With severe ischemia, development of optic disk and retinal neovascularization occurs.
      • Treatment. In addition to treating the underlying systemic condition, photocoagulation may be used when the ischemic condition is well established, the guidelines being the same as in the management of proliferative diabetic
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        retinopathy. To rule out lupus erythematosus vasculitis, lupus anticoagulant, an acquired serum immune globulin, should be considered in all patients with collagen vascular diseases, retinal artery occlusion, ischemic optic neuropathy, or transient visual loss or diplopia. It is important to recognize lupus anticoagulant in young and middle-aged patients not otherwise at high risk for stroke. Lupus anticoagulant and other vascular occlusive disease (see Chapter 9, Section V.A.3.c) may be screened for using anticardiolipin antibodies. Hyperhomocysteinemia has also been associated with retinal vascular occlusion disease (CRAO, CRVO). Consequently, homocysteine should be measured and folic acid given if it is elevated.
    • Retinal arterial occlusion
      • The branch retinal arterial occlusion (BRAO) may take hours or days to become clinically apparent as an edematous, whitish retinal infarction in the distribution of the affected vessel. Ultimately, the vessel recanalizes, resolving the edema but leaving a permanent visual field defect in the area of damaged retina.
      • Central retinal artery occlusion (CRAO) results in infarction of the inner two-thirds of the retina, reflex constriction of the whole retinal arterial tree, and stasis in all retinal vessels. CRAO may be preceded by transient ischemic attacks of visual blurring or blackout in embolic or inflammatory vasculitic disease (e.g., temporal arteritis). As in BRAO, bright cholesterol emboli (Hollenhorst plaques) from carotid atheromata may lodge at branch arterial bifurcations. The central infarct is ischemic; therefore, unlike retinal vein occlusion, hemorrhage is minimal. The retina at the posterior pole becomes milky white and swollen, and the choroid is seen through the fovea as a cherry-red spot. Usually the patient has painless loss of vision to 20/400 (unless the patient retains central vision via a cilioretinal artery supplying the papillomacular nerve fibers, occurring in 15% to 30% of patients). Vision with no light perception suggests choroidal ischemia due to ophthalmic artery occlusion in addition to the CRAO. Commonly, circulation is reestablished and the acute retina whitening resolves within a few weeks to months. The only clue that an eye without vision has had an old CRAO may be the loss of the B-wave with preservation of the A-wave on the ERG.
      • Histology. The retinal cells undergo necrosis, disintegrate, and are phagocytosed by macrophages. These macrophages appear to be foamy because of the high lipid content of the retina. In time, the edema and necrotic tissue are resorbed, leaving a thin retina with loss of bipolar cells, ganglion cells, and nerve fibers. Gliosis is minimal because glial cells are destroyed along with the nerve cells. Extensive hyalinization of the retinal vessels is seen in late stages.
      • Etiology. The most common cause of retinal arterial occlusion is embolization of the retinal vascular tree due to emboli arising from the major arteries supplying the head or from the left side of the heart. The emboli may be fatty material from atheromas, calcium deposits from diseased heart valves, septic and nonseptic fibrin, and platelet thrombi. In the absence of visible emboli, other causes include giant-cell (temporal) arteritis, collagen vascular diseases, oral contraceptives, and increased orbital pressure in conditions such as retrobulbar hemorrhage and endocrine exophthalmos. Rare causes include sickle cell disease and syphilis.
      • Treatment. Retinal arterial occlusion is an ophthalmic emergency, and prompt treatment is essential. Completely anoxic retina in animal models causes irreversible damage in about 90 minutes. However, because clinical occlusions may be partial, the following suggestions should be carried out immediately for anyone presenting within 24 hours of visual loss due to a CRAO. Specific precipitating events should be corrected (e.g., orbital decompression for acute retrobulbar hemorrhage or ocular hypertension from acute glaucoma). Nonspecific methods to increase blood flow and dislodge
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        emboli include digital massage, 500 mg i.v. acetazolamide and 100 mg i.v. methylprednisolone (for possible arteritis). A 95% oxygen–5% carbon dioxide mixture has been recommended in the past to dilate retinal vessels. However, after initially dilating vessels, this mixture induces a severe acidosis. The acidosis, in turn, will cause vasoconstriction and may induce cardiac arrest. Consequently, any gas containing 5% carbon dioxide should be used very cautiously or, better yet, not at all. Additional measures include paracentesis of aqueous humor to decrease IOP acutely. A sedimentation rate should be drawn to detect possible temporal arteritis. Improvement can be determined by visual acuity and visual field testing and by ophthalmoscopic examination. Patients with transient blurring of vision (amaurosis fugax) should have a thorough evaluation of the carotid artery. Amaurosis fugax demands urgent attention because it is a warning sign of an impending stroke. If carotid occlusive disease results in ophthalmic artery occlusion, general ocular ischemia may result in retinal neovascularization, rubeosis iridis, cells and flare, iris necrosis, and cataract. PRP appears effective in reducing the neovascular components and their sequelae (see Section III.B.5.f.[6]).
    • Retinal vasculitis is a complex group of conditions in which there is evidence of retinal vascular disease along with signs of inflammation, such as cells in the aqueous or vitreous. Fluorescein angiography shows staining of the vessel walls with leakage, ME, and all the other signs associated with ischemic response of the retina. Retinal vasculitis is seen in a number of etiologic conditions, such as temporal arteritis, Behçet syndrome, lupus erythematosus, polyarteritis, inflammatory bowel disease (Crohn), multiple sclerosis, sarcoidosis, syphilis, pars-planitis, masquerade syndrome, toxoplasmosis, and viral retinitis. Eales’s disease is idiopathic retinal vasculitis and is responsible for idiopathic vitreous hemorrhage, especially in young males. The etiology of Eales’s disease is obscure. Photocoagulation is of benefit if an ischemic response has been established with retinal and disk neovascularization.
IV. Acquired diseases of the macula
The basic pathology in these conditions appears to be confined to the choriocapillaris, Bruch membrane, and the RPE. The sensory retina is affected secondarily, in contrast to retinal vascular disease, in which the sensory retina is affected primarily. The choroid and the RPE may be affected by inflammation or degeneration that can be the result of a variety of factors, such as vascular, metabolic, or toxic influences. The response of the macula can be either a serous (or hemorrhagic) detachment of the retina or a primary atrophic or degenerative response. Fluorescein angiography is of great assistance in classifying these diseases. New therapies for the exudative components have greatly enhanced treatment over the older thermal laser techniques in the majority of conditions.
  • Serous detachment of the macula
    • Central serous choroidopathy (CSC)
      • Clinical characteristics. CSC, formerly called central serous retinopathy, usually occurs in young adult males and has an unknown etiology. The usual symptoms are decreased visual acuity, distortion, generalized darkening of the visual field, increased hypermetropia, and a decreased recovery from glare. Patients can be symptomatic even if their vision is 20/20. Ophthalmoscopy shows shallow detachment of the sensory macular retina, although the detachment may occur anywhere in the posterior pole. Fluorescein angiography demonstrates one or more points of progressive hyperfluorescence, demonstrating the site of origin of leakage through the RPE into the subretinal space. The leaking point may lie anywhere within the serous detachment and may or may not be associated with pigmentary changes seen clinically in the RPE.
      • Differential diagnosis. Serous detachment of the macula can occur in association with a congenital pit of the optic disc or choroidal neovascular membrane.
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      • Treatment. The disease usually lasts 1 to 6 months, and 80% to 90% of the patients recover good visual acuity, although mild metamorphopsia, color vision defects and faint scotoma may persist. The condition is not inflammatory in nature, and systemic steroids are not indicated. The duration of the disease, the initial visual acuity, the age of the patient, and laser treatment to the point of fluorescein leakage do not appear to have any effect on the final visual outcome. Almost all patients show some disturbance of the RPE, even after complete visual recovery. Duration of the disease for longer than 4 to 6 months, detectable morphologic changes in the retina (e.g., cystic edema and lipid deposition on the outer retinal surface), recurrence in eyes with previous CSC, and the need for prompt return of visual acuity are frequently accepted as indications for thermal laser treatment to the point(s) of fluorescein leakage.
    • Age-related macular degeneration (AMD, formerly called senile macular degeneration) is the chief cause of vision loss in patients over 50 years old in the United States. This condition has both a dry and a wet form.
      • Dry AMD. Drusen are the hallmark of dry AMD. They are commonly associated with RPE pigment mottling and geographic atrophy of the RPE and underlying choriocapillaris. Histologically, drusen are composed of basal laminar and linear deposits. The basal laminar deposits are long-spacing collagen between the plasma membrane and the basement membrane of the RPE. Basal linear deposits accumulate in the inner part of Bruch membrane. They consist of electron-dense granules and phospholipid vesicles. Clinically, drusen appear as yellow deposits deep to the retina. Their size is variable. Larger drusen are serous elevations of the RPE and inner part of Bruch membrane. Drusen are often associated with RPE clumping and atrophy. Areas of complete loss of the RPE with sharp borders are called geographic atrophy. In these areas, the choriocapillaris is missing, and the larger choroidal vessels stand out against the pallor of the underlying sclera. As long as the center of the macula is not involved with geographic atrophy, visual loss is usually mild in dry AMD.
      • Treatment of dry AMD is symptomatic with stronger near adds and low-vision aids as required. Recently, The Age-Related Eye Disease Study (AREDS) published that patients with dry AMD who take high-dose vitamins and zinc have a reduced risk of developing visual loss from advanced or wet AMD (23% versus 29% in placebo-treated patients). To be considered for this therapy, patients should have at least one drusen >125 μm in diameter or noncentral geographic atrophy. If drusen are <125 μm in diameter, they must be >63 μm in diameter and cover an area >360-μm-diameter circle if soft indistinct drusen are present or an area >656-μm-diameter circle if soft indistinct drusen are absent. Patients with advanced AMD or vision loss due to AMD in one eye should be treated. The doses of vitamins and minerals were as follows: vitamin C 500 mg, vitamin E 400 IU, beta-carotene 15 mg, zinc 80 mg as zinc oxide, copper 2 mg as cupric oxide (copper should be taken with zinc because high-dose zinc is associated with copper deficiency). This represents about five times the usual intake of vitamin C from diet alone, 13 times the recommended daily allowance (RDA) for vitamin E, and five times the RDA for zinc oxide. Several over-the-counter commercial preparations have this vitamin and mineral combination, such as Ocuvite PreserVision®. Smokers and former smokers should probably not take beta-carotene because other studies have shown an increased incidence of lung cancer in smokers who take this supplement. In addition, smoking is the one risk factor consistently associated with any form of AMD. Smokers can take formulations where Lutein has been substituted for beta carotene, such as Ocuvite PreserVision with Lutein®.
        Patients with dry AMD should also be tested with Amsler grids. If they notice distortion of the lines on the grid, they should contact their eye care professional immediately.
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        AMD is predominantly a disease of white persons, with an ill-defined inheritance pattern. When drusen are found in younger (<50 years old) individuals, they are sometimes called “dominant” or “familial” drusen, but the inheritance pattern is rarely proven. Some patients have cuticular or basal laminar drusen. Here, the drusen are myriad, especially on fluorescein angiography, and tend to be smaller. These eyes are prone to develop a central, subretinal, yellowish, soft-edged, deposit about three-fourths of the disk diameter in size, or a so-called vitelliform lesion. It is surprising that vision often remains reasonably good (greater than or equal to 20/80). Drusen must also be differentiated from pattern dystrophies (see Sections VI.B.5 and 6). These patients have central yellowish deposits, sometimes in specific shapes, such as a butterfly. These patients have a better prognosis than patients with AMD and usually retain good vision in at least one eye.
      • Wet AMD. Eyes with drusen or geographic atrophy that meet the AREDS criteria for treatment with vitamins and zinc (see Section IV.A.2.b) are at increased risk of developing the wet type of AMD. In this condition, the retina and RPE are detached from the underlying structures by serous fluid, and the subpigment epithelial space is occupied by blood vessels derived from the choroid, a choroidal neovascular membrane (CNV). The CNV may cause subretinal and subpigment epithelial hemorrhages. The subsequent organization of these hemorrhages and/or the normal maturation of the CNV gives rise to a typical subretinal fibrovascular disciform scar, most often located in the macular region. In contrast to dry AMD, eyes with wet AMD usually lose central vision fairly rapidly. The serous fluid leakage from the CNV detaches the RPE and/or the neurosensory retina, causing images to distort (metamorphopsia). The neurosensory detachment is often visible on careful binocular stereoscopic examination of the macula. Other signs of CNV on clinical exam include cystic changes in the central macula (cystoid ME), hard exudates, bright red subretinal blood, and dark gray subretinal pigment epithelial blood. Left untreated, the lesion will eventually develop into a white-appearing fibrous scar often associated with an extensive RPE atrophy and an overlying neurosensory detachment.
      • Treatment of wet AMD has been greatly enhanced through the development of biologic agents.
        • Biologic agents have focused on targets in the angiogenesis pathway. VEGF promotes both vascular permeability and neovascularization. VEGF is produced by Muller and RPE cells in response to ischemia. The biologic agents in clinical use are oligonucleotide aptamers, antibodies, and antibody fragments possessing selective affinities for VEGF-A. The binding of the agent to the VEGF molecule blocks its effect.
        • Ranibizumab (Lucentis) was approved in July 2006 for treatment of exudative AMD. It is an antigen-binding fragment of a humanized mouse monoclonal antibody against VEGF-A. Delivered as a monthly intravitreal injection, ranibizumab has a high affinity for all VEFG-A isoforms. It is FDA approved for all forms of wet AMD and is the first therapy to actually improve visual acuity (as opposed to just reducing the amount of vision lost) in wet AMD.
        • Bevacizumab, the full-length antibody from which ranibizumab was derived, is approved for treatment of specific malignancies under the trade name Avastin Bevacizumab has the same affinities (nonselective VEFG-A blockade) as ranibizumab and was widely used by ophthalmologists off-label as a first-line therapy for exudative AMD before ranibizumab gained FDA approval. Large-scale clinical trials have not been initiated for bevacizumab. The size of the antibody, 148kD, is often cited as a theoretical concern about its therapeutic mechanism. Nevertheless, bevacizumab continues to be an important option for AMD therapy.
        • Pegaptanib (Macugen) was approved by the FDA as the first anti-VEGF agent indicated for AMD. It was also the first aptamer therapeutic to
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          be used in humans. Pegaptanib is an RNA oligonucleotide with selective affinity for the VEFG-165 isoform. This subtype is thought to be the predominant form active in pathological neovascularization. It reduced the amount of vision lost but did not improve vision as ranibizumab did.
        • Photocoagulation. If the CNV does not involve the center of the macula, thermal laser can be used to ablate it with preservation of central vision. Treatment consists of high-energy, contiguous laser burns over and adjacent to the CNV. After the initial treatment, patients should be followed at close intervals with repeat fluorescein angiography because of a high risk of recurrence and, if necessary, treated again if residual or recurrent CNV is still present.
          Thermal lasers burn the retina overlying the CNV, leaving a permanent blind spot. Partial treatment of CNV is not advised because it often results in accelerated growth of or bleeding from the residual, untreated portion. Hence, if CNV extends under the center of the macula, treatment results in an instantaneous, profound, and permanent visual loss. Because many CNVs extend under the center of the macula, there was a great need to develop a way to treat subfoveal CNV without destroying either the overlying retina or underlying RPE-choriocapillaris complex that nourishes it.
        • Photodynamic therapy (PDT) or ocular photodynamic therapy (OPT). In response to this need, PDT was developed for treatment of subfoveal CNV in AMD before the anti-VEGF therapies described above. A light-activated dye (Verteporfin) is infused intravenously over 10 minutes. This drug preferentially attaches to lipoproteins, which are concentrated in the actively proliferating capillaries of the CNV. Fifteen minutes after the start of the infusion, the CNV is illuminated with laser light, the wavelength of which (689 nanometers) photoactivates the Verteporfin. The time of exposure is 83 seconds at an intensity of 600 mW/cm2 for a total dose of 50 J/cm2. This amount of laser irradiation does not cause a thermal burn. The photoactivated Verteporfin converts normal oxygen to a highly energized form called “singlet oxygen.” The singlet oxygen damages the endothelial cells of the CNV, causing their death and occlusion of the neovascular lesion.
          PDT slows the rate of visual loss but does not improve vision in wet AMD as ranibizumab does. It has to be repeated at 3-month intervals indefinitely because the CNV usually keeps recurring. It is not equally effective against all patterns of wet AMD and requires sophisticated interpretation of fluorescein angiograms to be applied effectively. It has been largely replaced by ranibizumab. However, it is probably an excellent treatment for CNV secondary to the ocular histoplasmosis syndrome, where it improved vision and often did not have to be repeated. It has also been used with success in CNV secondary to high myopia.
      • Other causes of CNV include any disease that disrupts Bruch membrane, or CNV can occur without apparent cause (idiopathic). Some of the more common conditions associated with CNV are
        • Ocular histoplasmosis syndrome (see Chapter 9, Section VIII.D.1).
        • High myopia.
        • Angioid streaks are dark lines radiating from the region of the disk and represent breaks in Bruch’s membrane. Angioid streaks occur bilaterally and may superficially resemble retinal vessels in their appearance and course. They are associated with pseudoxanthoma elasticum, Paget’s disease of the bone (osteitis deformans), sickle cell disease, and Ehlers-Danlos syndrome.
        • Traumatic choroidal rupture.
        • Drusen of the optic nerve.
        • Retinal dystrophies, such as Best vitelliform dystrophy.
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  • Pigment epithelial detachments (PED) are classified as serous or fibrovascular. Serous PEDs are dome-shaped elevations of the RPE with sharp borders that fill early and uniformly with dye on fluorescein angiography. They are seen in CSC and in AMD. In CSC, the prognosis for resolution and preservation of vision is good. In AMD, vision is usually fair until signs of associated CNV appear, such as subretinal pigment epithelial or subretinal blood, hard exudates, or irregular filling on fluorescein angiography. Fibrovascular PEDs are seen in AMD. They appear as a variable elevation or thickening of the RPE, which fills with dye irregularly and slowly during fluorescein angiography. The borders may be ill defined. These lesions are a form of occult CNV.
    No treatment is necessary for serous PED in CSC. Thermal laser ablation of extrafoveal serous PEDs and extrafoveal, well-defined, fibrovascular PEDs in AMD should be considered. Treatment of subfoveal serous PEDs in AMD can be delayed until signs of CNV develop. Then these lesions and subfoveal fibrovascular PEDs in AMD should receive ranibizumab or another appropriate treatment.
  • ME is thickening of the retina within 3,000 μm of the center of the macula. Cystoid macular edema (CME) is ME with numerous cystoid spaces and is usually due to abnormal perifoveal retinal capillary permeability, although leakage can come from beneath the retina as in CNV. ME and CME can be detected on slitlamp examination, fluorescein angiography (FA), and optical coherence tomography (OCT). Vitreitis and disk edema may be associated.
    • Numerous conditions are associated with ME and CME, including diabetic retinopathy, anterior or posterior uveitis, retinal vein occlusion (central or branch), retinitis pigmentosa, and ocular surgery (cataract extraction [Irvine-Gass syndrome], keratoplasty, glaucoma procedures, scleral buckle, photocoagulation, and cryopexy). Intraocular lens implantation at extracapsular cataract surgery does not increase the risk of CME. CME usually occurs 6 to 10 weeks postoperatively, and 75% of uncomplicated cases resolve spontaneously within 6 months. Surgical complications such as undue inflammation, vitreous loss, or iris prolapse increase the risk of CME and permanent vision impairment.
    • Extraocular medical treatment includes topical, periocular, and systemic steroids, especially for established CME, but the recurrence rate is high when treatment is stopped, thus the condition often requires long-term, low-dose topical steroids and occasionally a periocular drug, such as triamcinolone acetonide (Kenalog) 20 mg in 0.5 mL. Antiprostaglandin nonsteroidal anti-inflammatory drugs, such as topical ketorolac (Acular) or indomethacin 25 mg bid to qid orally (p.o.), are also useful over several weeks to months (see Chapter 9). The carbonic anhydrase inhibitor acetazolamide, p.o. 500 mg/day, is effective in some cases and may be added for several weeks to any of the above medications. Indomethacin p.o. 25 mg/day reduces the incidence of CME recurrence.
    • Intraocular medical treatment is commonly intravitreal triamcinolone acetonide (Kenalog) (4 mg in 0.1 mL) or, more recently, anti-VEGF agents, such as bevacizumab (Avastin) (1.25 mg in 0.05 mL). These therapies have been effective in ME and CME unresponsive to other forms of treatment such as focal laser in diabetic retinopathy or BRVO and useful as a primary treatment for ME and CME from CRVO.
    • Surgical treatment has been shown to be effective in cases where there is vitreous entrapment in the inner aspect of a corneoscleral incision. Removal of the entrapped vitreous via pars plana vitrectomy will frequently eliminate the CME. Yttrium, aluminum, and garnet (YAG) laser lysis of such vitreous adhesions has not been shown to be effective in a controlled trial.
  • Toxic maculopathies. Certain drugs have a toxic effect on the macula by producing degeneration of RPE and loss of vision. It is important to detect these changes at an early stage, by either fluorescein angiography or electrophysiologic diagnostic tests, particularly ERG (see Chapters 1 and 16).
    • Chloroquine. This aminoquinoline, along with hydroxychloroquine, is used in the long-term treatment of rheumatoid arthritis and lupus erythematosus. A
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      total dose of 100 to 300 g or more of chloroquine leads to a toxic effect on the macula characterized by a horizontally oval area of RPE atrophy, giving rise to a bull’s-eye appearance of the macula. Hydroxychloroquine is tolerated in large cumulative doses (1,000 to nearly 5,000 g) as long as the daily dose does not exceed 400 mg per day or 6.5 mg/kg body weight per day. Bull’s-eye maculopathy can be detected at its earliest stages by fluorescein angiography. The earliest functional changes are a relative or absolute scotoma to red, red-green defect on the Ishihara color test, an abnormal EOG, and elevation of threshold on static perimetry.
    • Thioridazine also has toxic effects on the RPE. Patients receiving high doses (>1 g/day) may develop pigmentary retinopathy with central or ring scotomas and diminished photopic and scotopic responses of the ERG.
    • Chlorpromazine, when taken in large doses (>2 g/day for a year), may cause mild pigmentary changes of the retina with no significant functional deficits.
  • Hereditary macular dystrophies. A number of genetically transmitted conditions such as Stargardt disease, Best vitelliform dystrophy, and cone dystrophy show a marked similarity in appearance to the toxic maculopathies (see Section VI.B, and Chapter 1).
  • Vitreoretinal macular diseases. Disturbances at the vitreoretinal interface are common causes of reduced central vision in elderly patients.
    • Idiopathic preretinal macular fibrosis, epiretinal membrane (ERM), cellophane maculopathy. These patients, who present with blurry vision and metamorphopsia (distorted vision), show a glinting reflex, traction lines (retinal striae), occasional CWS, and mild, gray preretinal fibrosis in the macula. These characteristics may arise spontaneously, may be related to vitreous detachment, or may be secondary to local vascular or inflammatory changes. Preretinal macular membranes may also arise after photocoagulation or after retinal detachment surgery. Pars plana vitrectomy with peeling of the epimacular membrane is done if there is significant visual loss due to epimacular membranes.
    • Senile macular holes. Idiopathic macular hole is a common cause of reduced central vision in otherwise healthy patients, usually women, in the sixth and seventh decades. Full-thickness holes must be differentiated from “lamellar” holes, cysts, and pseudoholes in idiopathic preretinal macular fibrosis. If a full-thickness hole is present, the patient will commonly state that there is a complete break in the middle of a thin line of light projected on the hole (positive Watzke-Allen sign). Small cuffs of subretinal fluid often surround these holes, and they are commonly associated with CME and epiretinal membranes. Ten percent to 20% of patients will develop a hole in their second eye. These holes rarely give rise to extensive retinal detachment. The cause of this condition is abnormal vitreoretinal adhesion and traction to the center of the macula. Vitrectomy with gas fluid exchange followed by face-down positioning can close a large number of holes and improve acuity. Peeling the posterior hyaloid, epiretinal membranes, or the internal limiting membrane increases the chance of hole closure.
V. Retinal inflammatory diseases
A variety of diseases cause inflammation primarily of the sensory retina, the RPE, or both the choroid and the retina. These diseases cause loss of central vision either by direct involvement of the macula or from secondary retinal edema or detachment from a paramacular lesion. Cells in the vitreous are always present.
  • Infectious chorioretinitis. A variety of bacterial and fungal agents can be carried to the retina and/or choroid as septic emboli. If the agent can be identified by cultures of blood, aqueous humor, or vitreous and appropriate therapy instituted immediately, many of these eyes can be saved with maintenance of varying degrees of visual function. Intravitreal antimicrobials and/or pars plana vitrectomy may be used to supplement systemic therapy in selected cases (see Chapter 9, Section VIII).
    CMV retinitis is commonly seen in AIDS patients with CD4 counts of less than 50. CMV retinitis must be differentiated from progressive outer retinal
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    necrosis (PORN)
    and toxoplasmosis. CMV is associated with more intravitreal hemorrhage and less vitreitis than toxoplasmosis. Like CMV, PORN has minimal vitreitis. However, the retina lesions in PORN have less hemorrhage than CMV. In the early stages, they appear as large, deep, ovoid areas of retinal whitening with minimal involvement of the overlying retinal vessels. The cause is usually varicella-zoster virus. In immunocompetent individuals, the same virus causes acute retinal necrosis and bilateral acute retinal necrosis. Here there is marked vitreitis and arteritis. Toxoplasmosis also occurs spontaneously in immunocompetent individuals. In this setting, acute retinal whitening is usually seen next to an old, pigmented toxoplasmosis scar, and there is an overlying focal vitreitis. Syphilis should not be forgotten as a cause of retinitis in immunocompetent or immunocompromised patients. Therapy is available for all of these conditions (see Chapter 9, Section VIII).
  • Infectious disease of the RPE. Certain viral diseases appear to primarily involve the RPE.
    • Rubella retinitis. Children born of mothers who contracted rubella in the first trimester of pregnancy show a high incidence of salt-and-pepper mottling of the RPE. Multiple other ocular and organ involvement may be present. In the absence of other ocular problems, such as cataracts or glaucoma, these children may have normal visual function. Fluorescein angiography shows mottled hyperfluorescence due to extensive and irregular loss of pigment.
    • Acute multifocal placoid pigment epitheliopathy (AMPPE) appears to involve the RPE, particularly in the macular region, causing visual loss with subsequent spontaneous resolution and residual pigmentation. The affected patients are young (average age 25 years) and often have a history of viral illness preceding the onset of visual symptoms, although a specific agent has not been identified. Bilateral involvement is present. One or more flat, gray-white, subretinal lesions are present in the posterior pole. These lesions block out background choroidal fluorescence during the early stages but stain in the late stages of fluorescein angiography. Healed, quiescent APMPPE may show extensive pigmentary changes and appear similar to atrophic macular degenerations or widespread retinal dystrophies. Unlike the latter conditions, patients with APMPPE retain good visual acuity and electrophysiologic function (see Chapter 9, Section X.C).
  • Retinochoroiditis (see Section V.A, Chapter 9, Sections VIII, IX, X, XI and Chapter 11, Section VIII). Focal or diffuse retinitis or choroiditis may be associated with a number of conditions, such as peripheral uveitis, sarcoidosis, and rare diseases such as Beçhet syndrome and subacute sclerosing panencephalitis.
VI. Retinal dystrophies
are genetically transmitted diseases of the retina that lead to premature cell changes and cell death (see Chapters 1 and 11). These conditions must be differentiated from congenital stationary retinal disorders, such as stationary night blindness or achromatopsia (autosomal recessive [AR]). Electrophysiologic tests are important in diagnosing these disorders, especially in young children, the main test being ERG. (See Chapter 1). An abnormality of the RPE photoreceptor complex plays a primary role in these diseases, with probable secondary abnormality of the choriocapillaris. In three conditions—retinitis pigmentosa, choroideremia, and sex-linked retinoschisis—the female carrier may show ocular signs. In most instances, the female carrier is asymptomatic and has normal test findings. Although a metabolic abnormality— hyperornithinemia—has been shown to be associated with gyrate atrophy of the choroid and retina, most retinal dystrophies do not appear to have any systemic or metabolic associations. Multiple mutations in multiple genes can cause retinitis pigmentosa, the most famous of these being the mutations in the rhodopsin gene.
  • Primary retinal dystrophies
    • Retinitis pigmentosa is the most common retinal dystrophy. The most common symptom is night blindness. Ophthalmoscopy demonstrates attenuation of the retinal vessels, retinal pigmentary changes consisting of bone-corpuscular clumping of pigment in the midperiphery of the fundus, and waxy pallor of
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      the optic disks. The visual fields show annular scotomas. The scotopic ERG is primarily affected; the photopic ERG is relatively spared. Patients tend to lose more rod than cone function in the early stages, as noted by ERG. This condition can be detected after age 6 based on abnormal ERGs often years to a decade before symptoms develop. Treatment of adults with 15,000 international units (IU) of vitamin A, in the palmitate form, on average, slows the progression of the disease. Doses for 6 year olds are 5,000 IU/day and for 10 year olds 10,000 IU/day. The website www.fightblindness.org/RetinitisPigmentosa/ lists mail-order companies that provide vitamin A palmitate in 15,000 IU capsules or tablets, as the correct dose is not available in most food stores. Note that beta carotene is not a suitable substitute for palmitate vitamin A. In addition, high-dose vitamin E (400 IU/d) appears to have an adverse effect on the course of this condition. Use of vitamin A can add 7 years of vision, and vitamin A plus two 3-oz servings of oily fish per week (sardines, tuna, mackerel, salmon, herring) can add 20 years of vision in RP patients. No toxic side effects have been reported with these vitamin A doses, but liver function and fasting serum vitamin A should be obtained once yearly.
    • Differential diagnosis of retinitis pigmentosa. A number of diseases and syndromes are associated with retinitis pigmentosa (see Chapter 11).
      • Acanthocytosis (Bassen-Kornzweig syndrome) is an AR disorder characterized by crenated red cells, serum abetalipoproteinemia, and spinocerebellar degeneration. In its early stages the pigmentary retinopathy can be reversed by large doses of vitamin A.
      • Alström syndrome is a rare AR disease whose clinical features include profound childhood blindness, obesity, diabetes mellitus, and neurosensory deafness. Chronic renal disease is seen in later stages.
      • Bardet-Biedl syndrome is an AR disorder characterized by polydactyly, obesity, mental retardation, and hypogonadism.
      • Cockayne syndrome is a rare, autosomally inherited condition. Afflicted patients have a prematurely senile appearance, mental retardation, deafness, peripheral neuropathy, and photosensitive dermatitis.
      • Friedreich syndrome is a recessively inherited spinocerebellar ataxia with deafness and mental deficiency.
      • Kearns-Sayre syndrome. The symptoms of this disease, which begins in childhood, include progressive external ophthalmoplegia and cardiac conduction defects. Early recognition and the use of a cardiac pacemaker may avert a fatal cardiac arrest.
      • Leber congenital amaurosis is an autosomal recessively inherited disease and is associated with profound visual loss at birth or in the first year of life. The ERG is nondetectable and provides an important means of differentiating retinal disease from “cortical blindness.”
      • Mucopolysaccharidosis. There are two types of mucopolysaccharidoses associated with pigmentary retinopathy. In Hunter syndrome (type II), the clinical features are gargoylism, mental retardation, hepatosplenomegaly, and early death. Sanfilippo syndrome (type III) is characterized by mental retardation, seizures, and deafness (see Chapter 11, Section XI.A).
      • Refsum disease is a recessively inherited condition characterized by peripheral neuropathy, deafness, and cerebellar ataxia. There is an increase of phytanic acid in the blood. Early dietary control consisting of withholding phytol, a precursor of phytanic acid, may retard neurologic and retinal changes.
      • Syphilis. Both acquired and congenital syphilis show extensive signs of pigmentary retinopathy.
      • Usher syndrome is an autosomal recessively inherited condition responsible for 3% to 6% of severe childhood deafness and 50% of deafness–blindness. Both the cochlear and vestibular systems are involved.
      • Pseudoretinitis pigmentosa. Certain retinal degenerations and inflammations may culminate in a clinical and electrophysiologic picture similar to that seen in retinitis pigmentosa. This condition is encountered with detachment
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        of the retina and following injury, especially concussive ocular injuries occurring early in life.
  • Primary macular dystrophies. Most macular dystrophies show ophthalmoscopic and retinal functional changes outside the macular area; however, their early manifestations are first seen in the macular area. All have varying degrees of central scotoma.
    • Vitelliform dystrophy (Best disease) is an AD disorder that begins in childhood and is characterized by an egg-yolklike lesion in the macular region bilaterally. It is compatible with near-normal visual acuity. The EOG is specifically afflicted; the ERG is normal. The yolklike material eventually absorbs, resulting in extensive pigmentary degeneration of the macula and a decrease in acuity.
    • Stargardt disease. This well-known macular dystrophy occurs between the ages of 6 and 20 years and is inherited as an AR condition. Unlike vitelliform dystrophy, Stargardt disease begins with rapid loss of vision with minimal ophthalmoscopic changes. Subsequently, the macula shows pigmentary disturbance. Many yellowish flecks surround this central area of beaten bronze atrophy. Central vision typically decreases to the 20/200 range, but the visual fields remain intact. The ERG is normal. On fluorescein angiography, there may be a dark choroid due to blockage of choroidal fluorescence by lipofuscinlike pigment in the RPE. Fundus flavimaculatus is reserved for cases without macular involvement, whereas Stargardt disease denotes atrophic macular dystrophy with fundus flavimaculatus.
    • Progressive cone or cone-rod dystrophy is an AD disease starting in the first to third decades and characterized by decreased central vision, severe photophobia, and severe color vision loss. There may be bull’s-eye maculopathy with a ringlike depigmentation around the center or the macula and optic disc pallor. Fluorescein angiography shows window defects and/or diffuse transmission defects in the posterior pole. Photopic ERG is very abnormal and scotopic ERG is near normal. The end stage has the same appearance as retinitis pigmentosa.
    • Familial drusen has its onset in the second to fourth decades and probably represents early AMD. Inheritance pattern is usually uncertain. There are no symptoms unless macular degeneration begins. The fundi have round yellow-white deposits of the posterior pole to midperiphery (drusen) that often coalesce. RPE detachment and CNV may develop, requiring laser photocoagulation. On fluorescein angiography, drusen may block then stain and the RPE is mottled. ERG is normal; EOG is abnormal.
    • Foveomacular vitelliform dystrophy, adult type, has its onset in the fourth to sixth decades and clinically resembles Best disease, except there is only a slight decrease in vision. The ERG and EOG are normal, and color vision slightly defective (tritan).
    • Butterfly dystrophy of the fovea is an AD disease with onset in the second to fifth decades and causes only a slight decrease in vision. It is one of the pattern dystrophies. The central macula has a butterfly-shaped reticular pattern, and there may be pigment stippling in the peripheral retina. Fluorescein angiography shows a reticular hyperfluorescence. The ERG and color vision are normal.
    • Central areolar dystrophy (choroidal sclerosis) is an AD disease with onset in the third to fifth decades that causes a slowly progressive decreased central vision. Early, there is mild foveal granularity. Later, RPE disruption, as well as geographic atrophy of the RPE and choriocapillaris, appears. Fluorescein angiography shows transmission defects early; later, there is late staining of edges of areas of geographic atrophy. The photopic ERG is abnormal and the scotopic ERG is essentially normal. Vision correlates with the degree and location of the pigmentary changes seen clinically, and color vision defect parallels vision loss.
  • Primary choroidal dystrophies (see Chapter 9, Section XI). The best-known disorders in this group are the sex-linked choroideremia, the AR gyrate atrophy of the choroid and retina, and the AD central areolar choroidal dystrophy.
  • Primary vitreoretinal dystrophies primarily affect the superficial retina and the vitreous body and include juvenile retinoschisis, Goldmann-Favre dystrophy,
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    Wagner disease, and clefting syndromes with palatoschisis and maxillary hypoplasia (see Chapter 11, Section X.D). These clefting syndromes are closely related to the Pierre Robin syndrome of glossoptosis, micrognathia, and cleft palate. Retinal detachment is frequently associated with clefting syndromes.
VII. Retinal detachment
In retinal detachment, fluid collects in the potential space between the sensory retina and the RPE, which remains attached to Bruch’s membrane. Fluid may accumulate by three major mechanisms. It may escape from the vitreous cavity into the subretinal space through a retinal hole or tear (break) in the retina. This type is called a rhegmatogenous retinal detachment. Extravasation from the choroid or the retina may result in retinal detachment in the absence of a tear or traction, termed exudative retinal detachment. Exudative detachments differ from rhegmatogenous detachments in that they do not extend to the ora serrata and shift with changes in head position (i.e., the subretinal fluid migrates quickly to the most dependent portion of the retina). They are also not associated with retinal breaks. Lastly, the retina can be detached from its normal position by contraction of adherent vitreous or fibrous bands, resulting in a traction retinal detachment.
  • Rhegmatogenous retinal detachment occurs more commonly in patients over the age of 45 years, males, and myopes. Rarely patients present with bilateral detachments.
    • Pathogenesis, signs, and symptoms. Rhegmatogenous retinal detachments usually occur in one of two ways. Rarely, they will result from the slow accumulation of fluid through a round hole or break in the peripheral retina. The patient’s only symptoms will be loss of side vision (frequently spontaneously described as a “curtain” by the patient) or loss of central vision when the macula becomes involved. More commonly, retinal detachment results from the relatively rapid flow of fluid through an acute tear created by an acute posterior vitreous detachment (PVD). The posterior vitreous is normally surrounded by a pseudomembrane, the posterior hyaloid. As the eye ages, pockets of liquefaction form in the vitreous in a process called “syneresis.” At some point in many people’s lives (about one-third by autopsy studies), fluid flows from one of these pockets of liquefaction through a hole in the posterior hyaloid, separating it from the back of the eye and creating the PVD. This typically happens very quickly, over minutes to hours. Frequently, fibrous tissue on the disc adheres to the posterior hyaloid as it separates and condensations form in the collapsed vitreous gel. These opacities throw shadows on the retina, and the patient complains of new floaters. The detached posterior hyaloid cannot separate from the peripheral retina, and in some patients it exerts intermittent traction on the peripheral retina, creating the sensation of bright, peripheral, split-second, light flashes (photopsia). In most patients, a retinal tear will not occur, the floaters become less noticeable, and the photopsia wanes. However, if the traction on the peripheral retina is great enough, a tear will occur. Fluid from the vitreous cavity can then flow through this tear, creating a rhegmatogenous retinal detachment. The patient will complain of a curtain coming over his or her vision, which corresponds to the area of the detachment.
      Ophthalmoscopy shows that the retina has lost its pink color and appears gray and opaque. If the collection of subretinal fluid is large, the retina shows a ballooning detachment with numerous folds. Binocular indirect ophthalmoscopy with scleral depression is valuable in locating the retinal breaks to repair the retinal detachment. Surgical reattachment should be performed as soon as possible as the macula undergoes cystic changes, with progressive degeneration of rods and cones, because the photoreceptors are separated from the choriocapillaris, their normal source of metabolic support.
    • Differential diagnosis of rhegmatogenous retinal detachment includes senile retinoschisis. This condition results from a splitting of the retina in older patients, particularly in the inferotemporal periphery. It appears as smooth, dome-shaped elevation unlike rhegmatogenous detachment, which is usually irregular in its contour. Other contrasting features with rhegmatogenous detachment include frequent bilateralism and lack of associated pigmentary
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      changes in the RPE. It produces an absolute field defect, whereas rhegmatogenous retinal detachment has a relative field defect. Thermal laser burns and cryopexy cause a visible white lesion on the outer wall of a schisis cavity, whereas no whitening is seen under a full-thickness retinal detachment because there are no retinal elements to turn white.
    • Risk factors for retinal detachment
      • Lattice degeneration of the retina is characterized by ovoid patches of retinal thinning with overlying vitreous liquefaction and abnormal vitreoretinal adhesions on their borders. These patches are usually concentric with the ora serrata and in the periphery. Sometimes crisscrossing white lines that represent atrophied retinal vessels are seen within these lesions; hence the term “lattice” degeneration. Pigmentary changes and round hole formation within the lesions are common. Small cuffs of subretinal fluid may form around the holes, but usually do not need treatment unless they extend beyond the borders of the lattice degeneration. Vitreous traction can cause large horseshoe breaks at the posterior margin of lattice degeneration when an acute PVD occurs. Lattice degeneration is present in 6% to 10% of patients and in about one-fifth to one-third of eyes with rhegmatogenous retinal detachment. However, the risk of developing retinal detachment in eyes with lattice degeneration is only 1%. Hence, prophylactic treatment with laser or cryopexy in asymptomatic eyes is usually not indicated.
      • Cystic retinal tufts appear as small elevations in the peripheral retina. They are associated with chronic traction on the retina by vitreous strands. Frequently, there is underlying hyperpigmentation of the RPE. When an acute PVD occurs, tears can occur at these tufts due to the abnormal vitreoretinal adhesions. About 5% to 10% of all rhegmatogenous detachments are associated with a cystic retinal tuft. Nevertheless, prophylactic treatment of asymptomatic lesions is usually not indicated because less than 0.3% of the 5% of eyes with this lesion will go on to have a retinal detachment.
      • Zonular traction tuft is similar to a cystic retinal tuft, but it is due to the insertion of a lens zonule into the peripheral retina.
      • Outer layer breaks in senile retinoschisis. There are often breaks in the thin inner layer of schisis. If outer layer breaks occur, fluid can then flow from the vitreous cavity through the inner layer breaks and then under the retina through the outer layer breaks. Outer layer breaks are usually large and round with thickened edges. They are easily treated with laser around their edges to prevent fluid flow under the retina, although in most instances they can be safely observed without therapy. The risk of a retinal detachment from double-layer holes in retinoschisis is about 1.4%.
      • Dialysis or disinsertion of the retina from its attachment to the ora serrata can occur spontaneously or as a result of trauma. Most dialyses occur in the inferotemporal retina, although superonasal dialyses can be seen after ocular contusion. A giant retinal break is when the tear extends 90 degrees or more along the circumference of the globe. It is often due to a traumatic dialysis.
    • Common peripheral conditions that do not predispose to retinal detachment are
      • Peripheral cystoid degeneration is generally found in eyes after age 20 years. These microcysts are considered to be a normal aging change and are located from the ora serrata extending backward into the retina.
      • Peripheral chorioretinal degeneration, also called “paving stone degeneration” and “cobblestone degeneration.” These lesions develop after 40 years of age. They are usually located inferiorly near the ora serrata and are bilateral. They appear as areas of complete RPE absence showing a few large choroidal vessels against bare sclera; they have sharp borders.
    • Treatment. Rhegmatogenous retinal detachment is treated with pneumatic retinopexy, scleral buckling, or vitrectomy. All retinal breaks are localized, and a chorioretinal adhesion is initiated around the break with diathermy, laser, or the cryoprobe. In pneumatic retinopexy, a gas bubble is injected into the vitreous cavity, and the patient is positioned so the gas pushes the retina around
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      the retinal break against the outside of the eye until the chorioretinal adhesion forms in 1 to 2 weeks. The subretinal fluid is resorbed by the RPE. In scleral buckling, the subretinal fluid is drained surgically, and the sclera overlying the retinal break is indented or buckled inward by sewing material to the outside of the eye. The buckled sclera pushes the choroid against the retina around the break, sealing the hole and allowing the chorioretinal adhesion to form. In vitrectomy, the vitreous pulling on the break is severed, and gas is used to then push the retina around the break against the choroid.
  • Secondary retinal detachments can occur with systemic or retinovascular diseases, or as a response to inflammation of the retina or choroid.
    • These conditions include
      • Severe hypertension, especially toxemia of pregnancy.
      • Chronic glomerulonephritis.
      • Retinal venous occlusive disease.
      • Retinal angiomatosis.
      • Papilledema.
      • Postoperative inflammation.
      • Primary or metastatic choroidal tumor.
      • Vogt-Koyanagi-Harada syndrome.
      • Retinal vasculitis.
    • The differential diagnosis includes choroidal detachments. Choroidal detachments have a solid, smooth, dome-shaped appearance. Their color is the orange-red of the normal fundus. They are common after intraocular surgery complicated by hypotony or inflammation.
    • Treatment is directed toward correcting the underlying condition. Secondary retinal detachments are not amenable to standard scleral buckling surgery. Systemic steroids are effective in Vogt-Koyanagi-Harada disease.
  • Traction retinal detachments are due to contraction of the vitreous after abnormal vitreoretinal adhesions have formed. They are most often seen in proliferative diabetic retinopathy, where the posterior hyaloid develops abnormal attachment to areas of new vessel formation on the surface of the retina. The leakage of fluid and blood from these new vessels and the vascular abnormalities within the retina stimulate the vitreous to contract. The vitreous then pulls on areas of adhesion to the retina, lifting the retina off. New membranes can form on the surface of the retina in rhegmatogenous retinal detachment and can contract. This condition is called proliferative vitreoretinopathy (PVR). The retina will not reattach because these membranes hold the retinal breaks away from the back of the eye. Other stimulants to membrane formation, contraction, and traction retinal detachments include intraocular foreign body, perforating ocular injury, and vitreous loss after cataract surgery. Pars plana vitrectomy with vitreous membrane cutting and pealing often reattaches the retina.
VIII. Retinal malignancy
IX. Vitreous
The vitreous undergoes significant physical and biochemical changes with aging. The most striking changes are liquefaction (syneresis) and posterior vitreous detachment (PVD) (see Section VII.A.1). Complications of PVD include retinal break and vitreous hemorrhage from either tearing superficial retina vessels or from the creation of a full-thickness retina break through the vascular retina. Syneresis and PVD occur an average of 20 years earlier in myopes than in emmetropes. Aphakic eyes have a much higher prevalence of PVD. Forward movement of the vitreous may be a reason for the higher prevalence of retinal detachment in aphakic eyes and for development of pupillary block glaucoma and malignant glaucoma.
  • Developmental abnormalities. Persistent hyperplastic primary vitreous (PHPV) and the various vitreoretinal dystrophies belong to this group. Eyes with PHPV, which are microphthalmic, develop cataract, pupillary block, and secondary glaucoma. Early intervention with a vitrectomy instrument to remove the cataract and retrolental tissue, either via the anterior or pars plana
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    approach, is advisable. Visual results are naturally poor because of the associated amblyopia.
  • Vitreous opacities
    • Blood. Vitreous hemorrhage usually comes from the retina and may be preretinal or diffusely dispersed in the vitreous cavity. Massive hemorrhages may reduce vision severely. The blood in a longstanding vitreous hemorrhage often becomes converted to a white opaque mass resembling an inflammatory exudate, endophthalmitis, or an intraocular tumor. A detailed history, along with a complete ocular examination combined with ultrasonography, usually establishes the diagnosis. The components of blood such as platelets and leukocytes probably contribute to the development of pathologic vitreous membranes.
      Vitreous hemorrhage and membrane formation are seen in a number of ocular conditions. Diabetic retinopathy is the most important cause, followed by retinal tear. Other conditions include PVD, retinal vein occlusion, sickle cell retinopathy, congenital retinal vascular anomalies, trauma, diskiform macular lesions, choroidal malignant melanoma, and subarachnoid hemorrhage.
    • Asteroid hyalosis is characterized by minute white or yellow solid bodies suspended in an essentially normal vitreous. This condition probably represents a dystrophy with fairly weak penetrance. Calcium soaps of palmitate and stearate are present in these vitreous deposits.
    • Cholesterolosis bulbi (synchysis scintillans) is typified by freely floating, highly refractile crystals in liquefied vitreous and is seen in eyes with severe intraocular disease.
    • Other conditions. Vitreous opacification can be seen in primary amyloidosis and large cell lymphoma. In retinoblastoma, tumor cells may be seen freely floating in the vitreous.
  • Inflammation. The response of the vitreous is characterized by liquefaction, opacification, and shrinkage whenever it is exposed to inflammatory insult. The vitreous is an excellent culture medium for the growth of bacteria, leading to endophthalmitis. The presence of white blood cells results in the laying down of fibrous connective tissue and varying degrees of capillary proliferation. Organization of these membranes may lead to a cyclitic membrane, formed by the cells from the ciliary body and the adjacent retina and located along the plane of the anterior hyaloid surface. Cyclitic membranes often lead to total retinal detachment. In addition to bacteria and fungi, vitreous abscesses with intense eosinophilia may be seen with parasitic infections, such as Taenia, microfilaria, and nematode infections due to Toxocara canis and Toxocara cati (see Chapter 9, Section VIII.C.).
  • Vitrectomy is the most significant advance in the surgical management of vitreous disease. The technique is used to clear vitreous opacities and relieve or prevent vitreoretinal traction. Vitrectomy through the pars plana approach is the best-established procedure. A variety of vitrectomy units are currently available. All instruments perform vitreous cutting and aspiration, the procedure being performed under microscopic control with the aid of fiberoptic illumination. The following are indications for pars plana vitrectomy:
    • Nonresolving vitreous opacities (e.g., diabetic hemorrhage).
    • Certain retinal detachments:
      • Traction detachments involving the macula.
      • Giant retinal tears.
      • Rhegmatogenous detachment with vitreous hemorrhage or PVR.
    • Macular diseases:
      • Preretinal macular fibrosis.
      • Macular hole.
      • Aphakic or pseudophakic CME with vitreous entrapped in corneoscleral incision,
      • Subinternal limiting membrane hemorrhage in the macula.
    • Trauma:
      • Penetrating injuries of the posterior segment with vitreous loss and vitreous hemorrhage.
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      • Double-penetrating injuries involving the posterior segment.
      • Selected magnetic and nonmagnetic intraocular foreign bodies.
    • Vitreous biopsy (amyloidosis, reticulum cell sarcoma).
    • Anterior segment reconstruction (pupillary membranectomy).
    • Vitreous complications in the anterior segment:
      • Vitreous “touch” with corneal edema.
      • Aphakic pupillary block glaucoma.
      • Malignant glaucoma.
    • Secondary open-angle glaucoma:
      • Hemolytic glaucoma.
      • Phacolytic glaucoma.
    • Endophthalmitis if initial vision is only light perception.
    • Severe proliferative diabetic retinopathy.
X. Trauma
(see Chapter 2, Chapter 9, Section XIV, and Chapter 11, Section XV). Ocular injuries often cause vitreoretinal and choroidal changes. Vitreoretinal trauma can be considered under the following headings.
  • Contusion injuries are caused either by a direct blow to the eye or from indirect force, as in head injuries or explosions. The force distorts the globe and alters pressure relationships in the retinal and uveal vessels. The following are the sequelae of contusion.
    • Commotio retinae appears as widespread deep retinal whitening with scattered hemorrhages following blunt injury to the globe. Damage to the outer segments of the rods and cones has been proposed as a mechanism. If the center of the macula is involved, vision is initially decreased. Vision usually recovers as the whitening resolves over several days to weeks, unless there are secondary pigmentary changes. No treatment is indicated.
    • Purtscher retinopathy, also known as traumatic retinal angiopathy, occurs after crushing injuries of the head, chest, or long bones. The condition is usually bilateral. The characteristic appearance is of multiple patches of superficial whitening with CWS and hemorrhages surrounding the optic disc. The whitening and hemorrhages disappear, but there may be some loss of vision. A similar picture can occur in acute pancreatitis, lupus erythematosus, and amniotic fluid embolization. The condition appears to be due to acute capillary ischemia.
    • Macular holes may occur following blunt trauma.
    • Choroidal ruptures are common following blunt trauma. They appear as curvilinear white lines at the level of the RPE concave toward the disc. Acutely, they are often associated with subretinal hemorrhages. Days to years later, CNV may grow from their edges.
    • Retinal tears or dialysis of the retina along with retinal detachment occurs after trauma. There is a high incidence of retinal dialysis after blunt trauma. This is a major cause of retinal detachments in children and young adults. Retinal dialysis appears to occur at the time of ocular contusion. If it is not recognized initially, it may go undetected until a symptomatic retinal detachment develops. Patients who have had blunt trauma should be examined periodically, especially if vitreous hemorrhage obscures part of the retinal periphery.
    • Retinal hemorrhages. The effects of retinal hemorrhages vary considerably according to their sizes and locations. Small retinal hemorrhages absorb completely without any significant visual defects. Hemorrhages trapped under the internal limiting membrane over the macula may induce epiretinal membrane formation and macular pucker.
    • Nonclearing vitreous hemorrhages may cause erythroclastic or ghost cell glaucoma, or they may organize, causing traction retinal detachment.
    • Occult rupture should be suspected in any eye with hypotony following blunt trauma. It commonly occurs just posterior to a muscle insertion. Careful exploration of the globe and closure of the rupture are indicated.
  • Perforating injuries of the posterior segment associated with vitreous loss and vitreous hemorrhage should be considered for vitrectomy to prevent retinal
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    detachment from PVR secondary to fibrovascular ingrowth. Similar considerations apply to eyes that have suffered a double perforating injury. Provided there is no retinal detachment, the surgery may be delayed for 2 to 3 weeks following the initial trauma to allow resorption of choroidals and formation of a PVD, thus simplifying the procedure.
    Endophthalmitis is always a risk in perforating injuries. Intravitreal injection of broad-spectrum antibiotics such as 1 mg of vancomycin in 0.1 mL and 2.2 mg of ceftazidime in 0.1 mL at the time of initial repair lessens this risk considerably. Five mcg of amphotericin B in 0.1 mL can be given as prophylaxis against fungal endophthalmitis. If intravitreal antibiotics cannot be given for technical reasons, the patient should receive 5 days of high-dose i.v. or oral antibiotics known to penetrate the vitreous in amounts effective against the most common organisms causing endophthalmitis such as linezolid (Zyvox), moxifloxacin (Avelox), or gatifloxacin (Tequin). Oral voriconazole (Vfend) can be used as prophylaxis against fungal infections.
  • Intraocular foreign bodies. A computerized axial tomography scan should always be done to rule out an intraocular foreign body in any perforating injury. Hammering steel on steel often sends up small chips from the hammerhead at high speed. These can enter the eye causing not much more than a foreign body sensation and a very small self-sealing entrance wound, which can be overlooked. Although most of these high-velocity steel foreign bodies are sterile, all foreign bodies must be assumed to be contaminated and prophylactic antibiotic therapy as for any perforating injury must be instituted. Depending on the velocity, shape, and mass of the object, it may come to rest anywhere in the eye or pass through the eye, causing a double perforating injury. In the latter case, the entry wound should be closed, but attempted closure of the more posterior wound can result in loss of intraocular contents and so should be avoided in most instances. Steel chips from hammerheads not uncommonly come to rest on the retina. Acute whitening rapidly develops around the touch site. After the removal of the foreign body, it is not necessary to treat the touch site with laser unless there is a frank retinal tear. It will scar to the choroid. If there is a double perforation or vitreous hemorrhage associated with vitreous loss, appropriately timed vitrectomy should be done as prophylaxis against retinal detachment from PVR secondary to fibrovascular ingrowth.
    Intraocular foreign bodies may be divided into two types, based on the ocular reaction they elicit (see Chapter 2, Section VIII).
    • Inert substances, such as gold, silver, glass, and plastics, cause no specific reaction in the eye based on their composition. Apart from traumatic infection and hemorrhage, these substances can cause slow liquefaction and opacification of the vitreous and fibroglial proliferation in the posterior segment, leading to retinal detachment from PVR. If they are loose inside the vitreous cavity, they can also cause retinal detachment by shredding the retina as they bounce off it with everyday eye movements.
    • Irritant metals. Iron and copper have serious effects on the eye (see Chapter 2, Section VII.B).
      • Iron foreign bodies. Siderosis is the complication of intraocular iron foreign bodies. The degree depends on the size, number of ferrous particles, and location in the eye. Retained iron, especially soft iron, undergoes electrolytic decomposition, combines with tissue cells, and causes eventual cell death. Siderosis affecting the retina results in diminution and ultimate extinction of the ERG. Iron can be demonstrated in tissues by Perls stain, a specific histochemical test. Late effects of siderosis include heterochromia, cataract, and secondary glaucoma. Treatment consists of removal of the foreign body, either by a magnet or with intraocular foreign body forceps usually in combination with vitrectomy. High-grade steel alloys are poorly magnetic and thus cannot be removed by a magnet.
      • Copper foreign bodies cause profuse suppuration in the eye. Copper is oxidized as readily as iron. Intraocular foreign bodies with copper cause chalcosis, signs of which include a greenish-blue peripheral ring in Descemet
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        membrane in the cornea, a greenish-red iridescent sunflower cataract, and retinal atrophy. Management consists of pars plana vitrectomy and removal of the foreign body using vitreous forceps.
  • Radiant energy. Ocular lesions can be produced by radiant energy of almost any wavelength. Vitreoretinal pathology is seen in the following conditions.
    • Solar retinopathy (foveomacular retinitis) refers to a specific foveolar lesion occurring in patients who gaze directly at a solar eclipse, sunbathers, and people gazing at the sun while under the influence of a hallucinogenic agent. Soon after exposure, these patients complain of metamorphopsia and a central scotoma. Vision is reduced to between 20/40 and 20/200, but almost complete recovery is seen over the ensuing months. During the period immediately after the exposure, a small gray zone develops around the foveolar area, resulting from photochemical injury to the sensory retina and the RPE. This zone is slowly replaced by a sharply circumscribed lamellar hole.
    • Radiation retinopathy describes alterations in the retinal vasculature in patients several months or years after receiving brachytherapy or heavy particle irradiation (e.g., proton beam) for intraocular tumor (e.g., malignant melanoma) or roentgen radiation to the skull and orbital region. An ischemic ocular response may be established as is seen in diabetic retinopathy. Macular function may be affected with decrease in central vision. Photocoagulation may be of value in controlling these complications.
    • Retinal phototoxicity. Wavelengths between 400 and 1,400 nm are transmitted by the mammalian ocular media to the retina, causing mechanical, thermal, and photochemical damage. Melanin granules in the RPE play a key role in mediating all three types of damage. Absorption of energy by the RPE and choroid causes elevation of temperature above the ambient temperature present in the neural retina, with thermal denaturation of sensitive macromolecules, such as proteins. Photochemical damage results from extended exposure of the retina by shorter wavelengths in the visible spectrum (450 to 550 nm). The lens absorbs wavelengths below 450 nm, with the result that fewer photons in the blue and near-ultraviolet region reach the retina.
      The physician, especially the ophthalmologist, should be aware of retinal irradiance levels for all ophthalmologic instruments such as ophthalmoscopes, intraocular fiberoptic light sources, surgical microscopes, and overhead surgical lamps. Infrared radiation should preferably be filtered from these sources because it causes actinic damage and does not contribute to visibility. Aging or diseased retinas may be more susceptible to actinic damage, compared to normal retinas.
XI. Lasers
have been a major therapeutic modality in the management of the retinocho-roidal and vitreal disorders. Lasers have been variously used to perform photocoagulation, photodisruption, photovaporization, and photoradiation.
  • Photocoagulation is the most commonly used modality. The incident light energy is absorbed and converted into heat by the pigment in the target tissues, such as RPE. The threshold temperature rise for retinal photocoagulation is approximately 10°C. Excessive temperature increase can cause vaporization and hemorrhage in target tissues. The wavelength of the incident light contributes to the efficiency of the photocoagulation process. Photocoagulation is used to (a) apply confluent burns under flat neovascularization not on the disc; (b) seal focal intraretinal leakage points; (c) perform grid therapy to areas of diffuse leakage and ischemia within the macula; (d) scatter PRP in the periphery to reduce angiogenic factor production by the oxygen-deprived retina; (e) focally treat RPE abnormalities, such as central serous choroidopathy; (f) obliterate extra and parafoveal choroidal neovascularization; and (g) produce chorioretinal adhesions as in scleral buckling surgery.
  • Photodynamic laser therapy (see Section IV.A.2.d.[6])
  • Laser types (see Chapter 10)
    • Most lasers used for photocoagulation are solid-state diode lasers. They can be used at the slitlamp or applied in the operating room using a fiberoptic probe
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      or a modified indirect ophthalmoscope. A variety of wavelengths are available. Green is a popular choice because it is absorbed by leaking red microaneurysms and the RPE. Yellow is even better absorbed by red microaneurysms and has the additional advantage of penetrating nuclear sclerotic cataracts better than green. Red and infrared wavelengths penetrate nuclear sclerosis, vitreous hemorrhage, and superficial retinal hemorrhages to some extent. Blue is to be avoided because it affects the treater’s retina and is absorbed by xanthophylls, resulting in extension of burns into the center of the macula.
    • The short-pulse neodymium (Nd): YAG laser is an example of a photodisruptor. This laser delivers a very high-power density in the pico-to nanosecond range (10-12 to 10-9 seconds), thereby ionizing tissue in a small volume of space at the laser beam focus, creating a “plasma.” The clinical Nd:YAG laser delivers energy in the near infrared (1064 nm) and is coupled with a helium–neon laser to provide a visible, red focusing beam that identifies the focal point of the invisible Nd:YAG laser beam. This modality is primarily used to disrupt relatively transparent targets in the anterior segment, such as lens capsular membranes and anterior vitreous bands.
    • Excimer lasers are currently being used to alter the refractive power of the cornea (see Chapter 6, Section V) by photovaporization.
    • Long duration, long wavelength diode lasers are used to treat intraocular tumors by photoradiation (see Chapter 11, Section XII, and Chapter 9, Section XVII).