DIAGNOSIS

Age-related macular degeneration (AMD) may be divided into two types. Nonexudative (“dry”) AMD has several morphologic forms, including “hard” discrete drusen, shallow retinal pigment epithelial detachments associated with thickened Bruch's membrane (“soft” drusen), and geographic atrophy (GA) of the retinal pigment epithelium (RPE).³ On FA the area of GA appears hyperfluorescent for window defect from the early frames of the angiogram, with late staining of the underlying sclera (Fig. 1). However, these pathologic changes can usually be assessed by clinical examination, and FA is generally not necessary to diagnose nonexudative AMD. An exception is cuticular drusen, which may appear clinically as a subtle disturbance of the RPE; FA reveals multitudes of small, discrete drusen described as “stars in the sky” (Fig. 2). The second type of AMD, which is associated with soft drusen, is known as exudative (“wet”) AMD. It is due to a choroidal neovascular membrane that has incompetent vessels resulting in detachments of the RPE and the neurosensory retina. Consequently, in patients with a large RPE and/or serous neurosensory detachment, FA is often necessary to rule out a choroidal neovascularization (CNV). In general, a small pigment epithelium detachment (PED) and a larger neurosensory detachment overlie CNV, while the opposite is generally the case in a nonexudative PED. Additionally, CNV often presents as a “notched” PED (Fig. 3).⁴ The presence of subretinal blood or pigment at the border of a PED strongly indicates that the detachment is exudative in origin (Fig. 4). Similarly, a rip in the RPE generally reflects subretinal fibrosis from a CNV (Fig. 5 and 6). The diagnosis is more difficult in patients who have a chronic, organized PED. Such a lesion may be due to either nonexudative AMD or to an organized, fibrotic CNV. Clinically and angiographically, it may be impossible to distinguish between these two conditions. In most cases, however, FA does assist in making the diagnosis.

In patients with a shallow neurosensory detachment, the Amsler grid test and visual acuity may be normal. If there is subtle elevation of the neurosensory retina on biomicroscopy examination, FA may demonstrate a CNV before it is symptomatic. It is often easier to evaluate both RPE and neurosensory detachments with good stereoscopic FA pictures than with direct examination.⁵ Consequently, FA can be helpful in determining the presence and extent of these processes. This is particularly important in patients with CNV due to AMD, because its aggressive course often requires prompt intervention to save central vision.^6,7

Furthermore, FA helps in recognizing two types of CNV: classic and occult. Classic CNV consists of a well-defined neovascular membrane, which is apparent in the early phase of the angiogram and shows late leakage of dye beyond its boundaries (Fig. 7 and 8). Occult CNV is seen on by FA as an area of late hyperfluorescence of undefined origin or as a neovascularized PED (Fig. 9 and 10 ). Mixed-type CNV is predominately classic or minimally classic depending on whether the classic component is more or less than 50% of the entire lesion (Fig. 11).

Fig. 8. A. Color photograph of subfoveal classic choroidal neovascularization (CNV). The neovascular membrane appears as a dirty gray, subfoveal lesion surrounded by exudative neurosensory detachment. B–D. Fluorescein angiography demonstrates early hyperfluorescence and late leakage of the CNV.

Fig. 9. A. Clinical photograph of the left eye of a patient with exudative neurosensory macular detachment. There were also intraretinal and subretinal hard exudates, subretinal hemorrhage, and retinal pigment epithelium (RPE) changes. B–D. Fluorescein angiography of the same eye demonstrates the presence of stippled hyperfluorescence from the RPE, and late-phase oozing of dye of undefined origin. There was occult choroidal neovascularization.

FA is also useful in characterizing two other subgroups of CNV: retinal angiomatous proliferation (RAP)^8–16 and polypoidal choroidal vasculopathy (PCV).^17–50 RAP begins in the deep retinal complex, forming intraretinal neovascularization (IRN), which may subsequently progress to extend beneath the neurosensory retina, forming subretinal neovascularization (SRN), and a vascularized PED.⁸ In the later phases of the process there may be a retinal-choroidal anastomosis (RCA). Clinical features of RAP include intraretinal hemorrhages, cystoid macular edema, and associated vascularized PED. FA is useful in revealing the presence of the angiomatous intraretinal vascular complex and the extension of the associated PED (Figs. 12 and 13). However, other diagnostic techniques such as indocyanine green (ICG) angiography, and optical coherence tomography (OCT) may be able to better demonstrate the presence of the RAP lesion.

Fig. 13. A. Early-phase Fluorescein angiography demonstrating the presence of an intraretinal angiomatous lesion (arrow). There is an associated pigment epithelium defect (PED), which is still hypofluorescent. B. Late-phase fluorescein angiography shows leakage from the retinal angiomatous proliferation (RAP) lesion and polling of dye into the PED. C. Indocyanine green angiogram of the same eye better demonstrates the presence of a hot spot corresponding to the RAP lesion. The PED remains hypofluorescent. D.Optical clearance tomography image demonstrates the presence of a serous PED and of intraretinal neovascularization.

PCV is characterized by the presence of dilated, choroidal vascular channels ending in orange bulging polyp-like dilations in the peripapillary and macular area. Associated features are recurrent subretinal hemorrhage and vitreous hemorrhage, relatively minimal fibrous scarring, absence of retinal vascular disease, pathologic myopia, and signs of intraocular inflammation. FA demonstrates the presence of the dilated vascular channel (Fig. 14 and 15). However, the presence of blood and exudation may block the details of the choroidal circulation on the angiogram. In these cases, ICG angiography can better demonstrate the presence of a distinct network of vessels within the choroid because the larger choroidal vessels are filled with dye.

Fig. 15. A 51-year-old Caucasian woman was referred with diagnosis of central serous chorioretinopathy in her right eye. A and B. Color photograph and red-free photograph of the right eye show the presence of atrophic changes in the retinal pigment epithelium consistent with central serous chorioretinopathy. C, Fluorescein angiogram of the right eye reveals the presence of avascular network of small-caliber vessels terminating in polyp-like structures. D. Indocyanine green angiogram of the right eye confirms the presence of the polypoidal lesion.

The FA can also distinguish CNV from simulating lesions. For example, a dark mound of blood due to hemorrhage from a CNV will block choroidal fluorescence, whereas vascular tumefactions such as choroidal hemangiomas leak fluorescein. Choroidal melanomas frequently block early choroidal fluorescence and then leak fluorescein from their intrinsic vascular network in later phases of FA.

TREATMENT

FA is vital for the management of CNV.^51–55 It can define the borders of the membrane and help localize the fovea. The final determination whether the CNV is subfoveal, juxtafoveal, or extrafoveal requires use of both FA to outline the membrane with respect to the retinal vasculature and clinical examination to define the precise location of the fovea (Fig. 16). Some patients, particularly those with high myopia, have an indistinct foveal avascular zone on FA. Other FA clues, such as the location of the macula lutea pigment, can be deceptive, because fixation does not necessarily correspond to the center of the macula lutea. The value of FA is also limited in cases of occult or poorly defined CNV, in which the exact location of the leaking CNV vessels cannot be angiographically determined (Fig. 17), and in patients with subretinal hemorrhage that obscures the membrane. In these patients, ICG angiography may be the most precise means of localization.

Conventional laser thermophotocoagulation is the treatment of choice for extrafoveal, well-defined, classic CNV. Photodynamic treatment (PDT) is the treatment of choice for subfoveal, predominantly classic CNV. FA is used to localize the lesion in relation to the fovea, classify the subtype, choose the type of procedure, and guide the treatment (Figs. 18, 19, and 20).^56–73

Fig. 20. A. Red-free photograph of a 20-year-old patient with sudden loss of vision to the level of 20/200. There is exudative, neurosensory macular detachment, a few hemorrhages, and lipid exudates. B. Fluorescein angiography reveals the presence of classic choroidal neovascularization (CNV), which appears to be juxtafoveal (<200 μ from fixation). Given the size of the CNV and its proximity to the fovea, it was decided to treat the patient with photodynamic treatment (PDT). C. Red-free photograph of the same eye 2 weeks after PDT; there is increased subretinal exudation D. Fluorescein angiography demonstrates that the CNV is still actively leaking. E. Red-free photograph 4 weeks after PDT demonstrates further increase in the size of the neurosensory macular detachment, subretinal hemorrhages, and lipid exudation. F. Fluorescin angiography reveals that the CNV has extended under the fovea. Given the young age of the patient, an inflammatory component of the neovascular process was suspected. It was decided to give a posterior, subtenon injection of triamcinolone acetonide, 40 mg/1 mL. G. Two weeks after steroid treatment there is partial reabsorption of the subretinal fluid. H. Fluorescein angiography demonstrates contraction of the CNV. I. Four weeks after injection of triamcinolone there is further reduction in the degree of neurosensory detachment; vision had improved to 20/60. J. Fluorescein angiography demonstrates that the CNV is smaller and less active (less leakage).

FOLLOW-UP

FA is needed to assess response to laser photocoagulation of a CNV and to diagnose recurrent membranes.^51,54 The authors generally obtain angiograms 2 weeks, 1 month, 3 months, and 6 months after treatment. The risk of recurrence is greatest during the first 3 months, and the patient, who often has decreased vision due to prior neurosensory detachment, may be asymptomatic. FA is also needed to evaluate the results of PDT. In the original protocol of the Verteporfin in Photodynamic Therapy (VIP) and Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) studies, a fluorescein angiogram was obtained every 3 months, and if there was persistent leakage from the CNV PDT was applied again (see Fig. 18–20).⁶⁰

DIAGNOSIS

Central serous chorioretinopathy (CSC) is characterized by breakdown of the outer retinal barrier, with leakage of fluid through a defect in the retinal pigment epithelium into the subretinal space, resulting in a serous neurosensory detachment.^78–205 The ophthalmologist can usually diagnose CSC based on the clinical examination and demographic information.^93–95 Most patients with CSC are middle-aged men⁷⁴ who often have type A personalities.^{75, 96–104} CSC has also been associated to the use of corticosteroids,^105–118 pregnancy,^119–126 increased adrenaline level and stress,^127–132 hemodialysis,^133,134 collagen vascular diseases,^135–147 and hypertension.^148–157 CSC typically presents as a large serous detachment in the posterior pole without an obvious source of the subretinal fluid.⁷⁶ However, because a small CNV cannot be ruled out, FA is usually done to confirm the diagnosis. Characteristically, there is a small RPE defect, which hyperfluoresces early, and then there is slow filling of the overlying neurosensory detachment, which may have a classic “smokestack” (Fig. 21) or “ink blot” (Fig. 22) appearance.^158–161 Occasionally, FA demonstrates multiple sites of leakage (Figs. 23, 24, and 25). FA sometimes fails to distinguish CSC from CNV readily because fibrinous subretinal precipitates can cause slow filling of the RPE detachment, which is suggestive of CNV (Fig. 26). Sometimes peripapillary PCV can cause a neurosensory macular detachment masquerading as CSC (Fig. 27).⁷⁷

Fig. 25. A 41-year-old man with the diagnosis of central serous chorioretinopathy in both eyes for 10 years presented complaining of sudden decrease of vision in the left eye. A. Red-free photograph of the right eye reveals pigmentary changes temporal to the fovea. B. Red-free photograph of the left eye shows a well-circumscribed neurosensory detachment of the macula with two areas of focal pigment epithelium detachment (PED). C– F. Fluorescein angiography shows two localized areas of PED and the typical “smokestack” appearance of the dye leaking under the detached retina. Note that the dye expands in an umbrella-like fashion once it reaches the upper limit of the detachment. G. Mid-phase fluorescein angiography of the fellow eye shows window-defect hyperfluorescence corresponding to the retinal pigment epithelium tract that extends inferiorly.

Fig. 26. A 36-year-old man presented with decreased visual acuity in the right eye. A. Color photograph of the right eye shows serous neurosensory detachment (white arrows) in the superior area of the macula with ring-like yellowish subretinal nodular deposits consistent with fibrin surrounding the localized pigment epithelium detachment (PED) (black arrows). B. Early-phase fluorescein angiography reveals a localized area of leakage corresponding to serous PED. C. Late-phase fluorescein angiography demonstrates hyperfluorescence due to pooling beneath the serous PED. D. Late-phase indocyanine green angiogram shows an area of hyperfluorescence corresponding to the serous PED with staining of the subretinal fibrin deposits.

The diagnosis of CSC may be difficult if there is neither RPE detachment nor evidence of leakage into the subretinal space. Possible causes of a neurosensory elevation without evidence of leakage in the macula include CSC with the RPE detachment located outside the macular area (Fig. 28), CSC with a healed leak (in which case the neurosensory detachment should resolve soon), peripheral retinal hole, choroidal tumor, congenital optic nerve pit, and idiopathic uveal effusion syndrome. There are several other considerations in a patient who presents with a localized serous detachment of the macula, including age-related macular degeneration,^162–164 a macular hole in a patient with high myopia, malignant hypertension, toxemia of pregnancy, collagen vascular disease, disseminated intravascular coagulation, choroidal inflammatory disease, Coat's disease (Fig. 29), and ocular contusion. Usually, these conditions are diagnosed based on clinical examination. ICG angiography may be helpful in differentiating CSC from AMD. On ICG studies there is often diffuse choroidal hyperpermeability in patients with CSC.^165–181

Fig. 29. 14-year-old adolescent girl with sudden loss of vision in the left eye to 20/400. A. Clinical photograph of the posterior pole demonstrates a neurosensory macular detachment simulating central serous chorioretinopathy. B. Composite fundus photograph of the same eye demonstrates the presence of a localized area of retinal capillary telangiectasia in the temporal periphery. The intraretinal yellowish material is consistent with dehemoglobinized blood. There are also intraretinal exudates scattered throughout the fundus. C. Composite fluorescein angiogram of the same eye reveals diffuse retinal capillary telangiectasia and intraretinal leakage. The dilated retinal telangiectatic vessels are actively leaking and are responsible for the macular neurosensory detachment. This patient was diagnosed with Coats' disease. D. Scatter laser photocoagulation of the telangiectatic vessels was carried out.

TREATMENT

The clinical course of CSC tends to be benign, with complete resolution within 3 to 4 months.⁷⁴ Focal laser treatment of small RPE detachments has never been shown to improve the long-term vision of patients with CSC,⁷⁸ but it does hasten resolution of the neurosensory detachment and it reduces the recurrence rate.^79,182–203 The best candidates for treatment include those who have occupational needs and are strongly motivated to undergo treatment, and those with a chronic neurosensory detachment of 4 months or longer, particularly if there is evidence of loss of central or paracentral vision.⁵⁵ Laser treatment to the point of RPE leakage is very effective in resolving the neurosensory detachment.^80,81 In chronic CSC, grid treatment reduces macular edema and lipid and tends to stabilize vision.^82,83

FOLLOW-UP

FA is rarely needed to follow the course of patients with CSC. As the subretinal fluid resolves, patients will have improved visual acuity, decreased metamorphopsia, and decreased induced hyperopia. Contact lens biomicroscopy reliably evaluates the amount of subretinal fluid. If the neurosensory detachment persists for several weeks after laser treatment, FA can be valuable in elucidating whether the RPE detachment has failed to resolve despite treatment, whether there have been unnoticed RPE defects that were not treated, whether there is recurrent CSC, or whether there is another cause of neurosensory detachment.

Although several authorities consider CSC to be a relatively benign disease,⁸⁴ some patients develop recurrent, chronic neurosensory detachments that slowly cause photoreceptor degeneration. These patients often have a diffuse RPE “ooze,” reflecting generalized RPE dysfunction (Fig. 30). Their persistent neurosensory detachment can eventually lead to significant visual loss.⁸⁵

Clinically discernible peripheral dependent bullous neurosensory detachments have been described in patients with chronic CSC.^85–92 Yannuzzi and co-workers first characterized the presence of RPE atrophic tracts extending inferiorly in the fundus periphery secondary to antecedent retinal detachment in patients with CSC.⁸⁵ Presumably, there is a particularly severe and/or longstanding leakage of fluid from an RPE defect in the subretinal space at the posterior pole. The subretinal fluid gravitates inferiorly to form a dependent neurosensory detachment in a “flask,” “teardrop,” “dumbbell,” or “hourglass” pattern (Fig. 31). Sometimes the tract of subretinal fluid connecting the macular detachment with the bullous neurosensory detachment in the inferior hemisphere is so shallow that it is very difficult to appreciate. The RPE under the chronic retinal detachment experiences atrophic changes that appear as atrophic RPE tracts connecting the posterior pole with the dependent retinal detachment. The retina itself develops secondary manifestations including pigment migration, capillary dilatation (telangiectasia) proximally and capillary nonperfusion (ischemia) distally to the area of detached retina (see Fig. 31). The changes in the RPE consist of both RPE atrophy and pigment clumping in the form of perivascular deposits or bone spicules, a condition described by Gass as a “pseudoretinitis pigmentosa–like atypical CSC presentation.”⁸⁷

Fig. 31. A 47-year-old woman with an18-year history of central serous chorioretinopathy in both eyes. A. Color photograph composite of the left eye shows bullous dependant detachment of the neurosensory retina inferiorly. B. Fluorescein angiogram composite reveals diffuse decompensation of the retinal pigment epithelium, multiple scattered pigment epithelium detachments 9PEDs), and obliteration of the retinal capillaries in the region of the detachments. Note the presence of early neovascularization at the junction between perfused and non-perfused retina. C. Clinical photograph of the left eye shows PED superior to the optic disc partially surrounded by fibrin deposits. D. Fluorescein angiography confirms the presence of active leakage from the serous PED. E, Color photograph composite of the same eye 2 months after laser treatment of the site of leakage reveals partial resolution of the detachment and lipid precipitation. F. Clinical photograph composite 16 months after the laser treatment in the area of the leakage shows complete resolution of the detachment and partial reperfusion of the inferior retina.

Other complications noted in these patients are cystoid macular edema or, more frequently, cystoid retinal changes in the areas of chronic detachment, subretinal lipid deposition, choriocapillaris atrophy secondary to the RPE damage in the areas of RPE tracts, and CNV.^{89,90,204–206} This severe variant of CSC appears to be more frequent in patients of Latin or Asian ancestry, and it is usually associated with frequent recurrences, permanent central vision loss, and significant superior visual field loss.

DIAGNOSIS

Epiretinal membrane (ERM) formation has been associated with retinal vascular occlusive disease, diabetes, uveitis, penetrating or blunt trauma with intraocular hemorrhage, ocular inflammation, ocular surgery, laser or cryotherapy for retinal breaks, telangiectasia, macular holes, retinal angiomas, retinal arteriolar macroaneurysms, intraocular tumors, and retinitis pigmentosa.²⁰⁷ A preretinal sheen, readily appreciated on direct ophthalmoscopy or contact lens biomicroscopy, provides a diagnosis. In more severe cases, a fibrous membrane and distortion of the retinal vessels can be seen (Fig. 32). Consequently, FA is generally not necessary to confirm the diagnosis of ERM. Nevertheless, FA can demonstrate leakage from vessels that have become relatively incompetent owing to traction from the membrane (Fig. 33).^208,209 This often accounts, in part, for loss of vision in symptomatic patients. OCT examination is the gold standard for the study of the vitreoretinal interface. It nt only demonstrates the presence of an ERM,, but also helps in quantifying the degree of tractional neurosensory elevation and in differentiating an ERM from vitreomacular traction syndrome.

TREATMENT

An ERM that causes severe loss of vision may warrant vitrectomy and membrane peeling. In these cases, the membrane is clinically obvious and FA is not necessary. Ultrasound is often useful to assess the degree of posterior vitreous separation from the posterior pole.^210–212

FOLLOW-UP

FA plays no role in the chronic management of patients with ERMs. The clinical presentation, including visual acuity, Amsler grid, and fundus appearance, guides long-term care.

DIAGNOSIS

In general, the diagnosis of a macular hole is readily made in patients who present clinically with a full-thickness retinal defect, yellow exudative deposits at the base, and, occasionally, an operculum. However, it is sometimes difficult, using contact lens biomicroscopy alone, to distinguish a full-thickness macular hole from simulating conditions. Visual acuity is often 20/200 to 20/400 in an eye with a full-thickness hole, whereas eyes with macular cysts or pseudoholes usually have better vision. Visual acuity, however, cannot rule in or rule out a full-thickness macular hole.^213,214

The differentiation of a partial-thickness, or lamellar, macular hole from a full-thickness macular hole can be challenging, and FA is often helpful in assisting in the diagnosis.⁵⁵ As in a full-thickness hole, a lamellar hole presents as an excavation of the retina, and the presence of drusen underneath the lamellar hole can simulate the yellow deposits seen at the base of full-thickness holes. Occasionally, there is a full-thickness hole at one side of a lesion, and the rest of the lesion consists of a lamellar defect. FA will show immediate hyperfluorescence from the choroidal circulation under a full-thickness hole (Fig. 34A), whereas a lamellar hole, with a relatively intact RPE, will block some of the normal fluorescence from the choriocapillaris (Fig. 34B).

There are several causes of pseudoholes, including an area of sharply demarcated RPE atrophy, a dilated perifoveal capillary net, and an ERM with a clear center. Careful contact lens biomicroscopic examination will usually distinguish these conditions from a full-thickness macular hole, but FA can help. Both RPE atrophy and a full-thickness hole will exhibit window defects, but RPE atrophy tends to have more residual pigment and consequently a more mottled appearance of the transmitted choroidal fluorescence. A dilated perifoveal capillary net, which can be seen in diabetes or perifoveal telangiectasia, will leak fluorescein. A pseudohole will not have a window defect.

OCT examination is the most accurate test for differentiating full-thickness macular holes, lamellar holes, and pseudoholes.^215–230

Autofluorescence imaging, a novel technique for diagnosis of macular holes, is based on the principle that the autofluorescence signal from the RPE is not blocked by the retinal pigments in the presence of a full-thickness macular hole; as a result, a full-thickness macular hole presents a bright autofluorescent signal, whereas pseudoholes and lamellar holes are not autofluorescent (Fig. 35). This technique has the advantage, compared with FA, of not requiring dye injection.

TREATMENT

It is recommended to observe a stage 1 macular hole, since half of these will undergo spontaneous resolution. The treatment for stage-2 through stage-4 macular holes is surgical repair.^231–238 The pseudohole itself is not visually disabling, but the condition may be clinically significant if there is considerable vitreoretinal traction such that the lesion threatens to develop into a full-thickness hole.

FOLLOW-UP

Just as the clinical findings of these conditions are most important for initial diagnosis and treatment, the findings on clinical examination guide long-term management.

DIAGNOSIS

FA is generally not necessary to make the diagnosis of cystoid macular edema (CME). A history of recent cataract surgery, diabetes, uveitis, or other predisposing conditions is usually obtained. Clinically, the patient presents with retinal thickening, often with clinically evident cystic changes. FA reveals a characteristic petaloid collection of fluorescein that confirms the diagnosis, which has been shown histologically to reflect accumulation of fluid in the extravascular component of the outer plexiform layer.²³⁹ When FA demonstrates leakage from the optic nerve, this suggests an inflammatory etiology for the CME (Fig. 36). Although this sign is reliably present in CME associated with cataract surgery, penetrating keratoplasty, or posterior uveitis, it is not characteristically present in diabetics or in idiopathic CME. FA can also demonstrate dilated macular capillaries as a cause of CME in diabetes (Fig. 37). Different conditions that may cause CME include Irvine-Gass syndrome, previous penetrating keratoplasty, any inflammatory condition that involves the posterior segment, peripheral rhegmatogenous retinal detachment, peripheral cryotherapy, malignant melanoma, topical epinephrine, tapetoretinal degenerations, juxtafoveal telangiectasia, occult central retinal vein occlusion, nicotinic acid maculopathy, and idiopathic CME.

There are several conditions that may be confused with CME, including juvenile X-linked retinoschisis and Goldmann-Favre disease. FA can assist in making the diagnosis if it is not apparent on clinical examination.

TREATMENT

FA does not help guide treatment of CME, which should address the underlying cause. For example, posterior uveitis is generally managed with corticosteroids, wherease aphakic CME may benefit from steroid, antiprostaglandin, and acetozolamide therapy.^240–250

FOLLOW-UP

FA is often used to assess the response to therapy. Decreased fluorescein leakage can be a sensitive indicator of improvement, particularly when visual acuity is reduced to a level that makes subtle visual changes difficult to gauge. FA does not assist in prediction of the likely visual outcome. Although CME tends to resolve in some conditions, such as Irvine-Gass syndrome, patients with CME due to other causes such as diabetes generally suffer some irreversible loss of central vision.

DIAGNOSIS

The diagnosis of degenerative myopic maculopathy is clinically obvious. Patients with pathologic myopia are, however, at risk for development of CNV, and FA is helpful in their diagnosis and treatment.^251–255 Patients with myopic degeneration have pigmentary changes that can be difficult to distinguish from small neovascular membranes. CNV in pathologic myopia tend to be smaller and less aggressive than the neovascular lesions of age-related macular degeneration.⁵⁵ CNV in myopic eyes can often be strongly suspected on clinical grounds, using clues such as subretinal blood or lipid exudate, neurosensory elevation, and appearance of a gray membrane visible through atrophic RPE (Fig. 38). FA is sometimes helpful in distinguishing a neurosensory detachment due to a small macular hole from retinal elevation from leaking CNV. FA has been also valuable in demonstrating an association between Fuchs' spots and CNVs²⁵⁴ and in identifying disturbances of choroidal and retinal blood flow in pathologically myopic eyes.²⁵⁵

TREATMENT

The value of treating CNV in highly myopic patients is controversial. The CNV generally does not grow extensively, there is considerable risk of rupturing Bruch's membrane, and the laser burn chorioretinal scar tends to enlarge substantially.^251,252 Nevertheless, there is evidence that patients with pathologic myopia who receive treatment for CNV have better final visual acuity.²⁴³ FA often helps define the extent of CNV, but it has limited value in assisting the localization of the fovea. PDT has proved to be a useful option for the treatment of subfoveal CNV in myopia.²⁵⁶

FOLLOW-UP

FA is useful in evaluating the efficacy of treatment of CNV and in determining whether recurrent CNV has developed. Patients with subfoveal CNV are likely to lose central vision. The diagnosis and prognosis of atrophic myopic degeneration is best determined by clinical appearance.

DIAGNOSIS

Trauma can induce a wide spectrum of alterations of the retina, RPE, and choroid. Most types of traumatic maculopathy, such as Purtscher's retinopathy, Berlin's edema, retinal contusion, traumatic macular hole, and choroidal rupture, are readily apparent on clinical examination.²⁵⁷ Choroidal rupture, althoughe usually evident clinically, may be more obvious on FA (Fig. 39). Contusion necrosis of the RPE may present clinically with an associated RPE detachment, an overlying neurosensory detachment, and a subtle change in RPE pigmentation. FA can demonstrate the site of leakage into the subretinal space, unless the RPE defect has healed by the time of testing. FA is particularly helpful in differentiating retinal concussion (Berlin's edema), in which FA findings are normal, from retinal contusion, in which there is RPE damage and, consequently, increased transmission of choroidal fluorescence on FA.²⁵⁷ In Purtscher's retinopathy, FA can document vascular closure, which accounts for the retinal infarctions (Fig. 40).²⁵⁸

TREATMENT

FA can define the locations of CNV in patients with choroidal rupture, which may be amenable to laser therapy.

FOLLOW-UP

Most trauma-related conditions are followed clinically with serial evaluations of clinical appearance and visual acuity. Routine FA to follow trauma-related maculopathies is not necessary.

Patients with choroidal rupture through the fovea, which is generally obvious clinically, lose central vision. In retinal contusion, a normal fluorescein angiogram indicates a good visual prognosis, wherease fluorescein leakage is associated with tissue damage, and nonperfusion carries a poor visual prognosis.²⁵⁷ The outcome of Purtscher's retinopathy and of RPE contusion largely depends on the location of macular involvement. Patients who suffer a macular hole are usually left with approximately 20/400 (6/120) vision.

TOXIC RETINOPATHIES

Many drugs, metals, and inorganic compounds can induce maculopathy.²⁵⁹ Among the most clinically important macular toxins are chloroquine and hydroxychloroquine, which are commonly used in the U.S. to treat severe systemic lupus erythematosus and rheumatoid arthritis. Thhe ophthalmoscopic appearance of a ring of RPE alterations in the parafoveal area may be more sensitive than FA for detecting early chloroquine retinopathy.²⁶⁰ Also, self-administered Amsler grid testing is a simple and efficient means of detecting early retinopathy in many patients.²⁶¹ As the maculopathy progresses, FA can readily detect RPE atrophy that extends peripherally and also advances centrally to involve the fovea (Fig. 41).

Oxalosis, which results from calcium oxalate deposition, can be due to an inborn metabolic disorder (primarily hyperoxaluria), ethylene glycol ingestion, or methoxyflurane general anesthesia.^262–264 Clinically, patients have a crystalline retinopathy, and FA may show RPE hyperplasia, fibrous metaplasia, and choroidal neovascularization.⁵⁵

Epinephrine induces CME that is generally diagnosed on clinical grounds. This condition occurs more commonly in aphakic patients. The maculopathy typically resolves with cessation of the drug, and FA can be useful to document resolution of the edema. Epinephrine-induced CME evidently increases retinal capillary permeability, but the pathophysiology of this process is poorly understood.²⁶⁵

Tamoxifen, an antiestrogen drug used in some cases of breast cancer, has a characteristic clinical picture.²⁶⁶ FA may reveal Tamoxifen-induced CME from capillary hyperpermeability and RPE alterations.

Clofazimine is an antimycobacterial agent that has been used since 1962 to treat dapsone-resistant leprosy and, more recently, to treat Mycobacterium avium-intracellulare complex infection in patients with acquired immunodeficiency syndrome (AIDS). There have been two reports of bull's eye maculopathy with multiple RPE defects demonstrated on FA (Fig. 42).^267,268

Gentamicin and tobramicin toxicity, which often result from inadvertent injection into the vitreous during cataract surgery, cause devastating retinal damage. In areas where high concentrations of gentamicin reach the retina there is obliteration of the retinal vasculature and ischemic necrosis of the retina (Fig. 43).^269,270

A number of other drugs, chemicals, and metals can induce retinopathy that manifests clinical and angiographic findings, including desferrioxamine, canthaxanthine, nicotinic acid, iron, and copper. Other texts deal with these conditions in greater detail.^55,271

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