Ординатура / Офтальмология / Английские материалы / Ophthalmic Care for the Comabat Casaulty_Thach_2003

Fig. 15-13. Vitreous changes secondary to the presence of an intravitreal copper foreign body. A marked fibrillar degeneration and brownish tinge of the vitreous is apparent. Reproduced with permission from Rosenthal AR, Marmor MF, Leuenberger P. Chalcosis: A study of natural history. Ophthalmology. 1979;86:1962.

cosis experience more than a 50% reduction in b- wave amplitude. Moreover, after the ERG amplitudes fall to a certain level, they may remain stable without further deterioration for many years.25 In addition to ERG observations in humans, electrophysiology studies4 in rabbits have demonstrated that chalcosis causes far less damage than siderosis does. It is widely assumed that ERG changes of chalcosis are reversible, based on case reports of complete resolution of all clinical signs following removal of the instigating IOFB.26 These case reports, the relatively benign nature of ERG changes in chalcosis, and the reversibility of ERG changes in siderosis after removal of ferromagnetic IOFBs all support the presumed ERG reversibility in chalcosis. However, no published case reports have actually documented reversibility.

Pathophysiology

Copper’s interaction with intraocular fluids and tissues causes its ionization. Most copper ions become coated with zinc oxides, and this coating minimizes the potential for tissue toxicity. These coated ions have a propensity to be deposited on limiting membranes, in contrast to the tendency of iron particles to be distributed intracellularly. The most common ocular structures affected are Descemet’s membrane, the anterior lens capsule, and the internal limiting membrane of the retina.1,2

Metallosis Bulbi

As stated in the discussion of siderosis, the lack of intracellular deposits of toxic particles likely accounts for the more benign clinical course in chalcosis. In the rare case in which an IOFB contains more than 85% copper, the sterile endophthalmitis that develops is attributed to copper’s chemotactic properties. The severe inflammatory response is characterized by abscess formation in the vitre-

ous.2,24,27

Distribution of ions within the eye may be related to the standing electrical potential.5 The cornea exhibits a positive charge relative to the optic nerve, which may induce ion distribution based on electrostatic forces. It is unclear why the macular region is selectively predisposed to copper deposition. Some observers26 have speculated that it may be linked to the macula’s higher metabolic rate as well as fluid movements in the eye. It is quite likely, however, that other factors are involved, because this theory fails to explain why siderosis initially affects the peripheral retina.

Vitreous opacification results from the degradation of hyaluronic acid, as is also seen in siderosis. Depolymerization of hyaluronic acid is associated with oxidation of ascorbic acid, and copper is known to accelerate the oxidation of ascorbic acid.

Clinical Course

The clinical course of chalcosis is variable but generally less severe than it is in siderosis, and chalcosis does not have a uniformly poor outcome. The extent of damage and visual impairment depends on several factors, including the size, alloy composition, and intraocular location of the IOFB, and adjacent tissue reaction. A retained copper-contain- ing IOFB can be tolerated for years without serious toxicity to the retina or RPE.

One case series25 reported on 10 patients with retained IOFBs of copper alloys who were followed from 4 months to 29 years; 9 of the 10 patients retained a final visual acuity of 20/60 or better. All 10 had clinical findings typical of chalcosis. IOFBs located in the vitreous were more likely to cause chalcosis, whereas in the anterior segment or the lens nucleus, small FBs could cause very few changes typical of this disease. Not all patients with chalcosis will maintain such a high degree of visual function. The two clinical findings that have the most deleterious impact on vision are (1) vitreous opacification and (2) macular toxicity.

The time for clinical signs of chalcosis to develop ranges from 4 months to 2 years.25 Most of the ocular findings may resolve spontaneously if the IOFB

Ophthalmic Care of the Combat Casualty

dissolves, is spontaneously extruded, or is surgically removed.28 In addition to the effects on visual acuity, abnormalities in color vision and visual field have been reported.25 It is unclear, however,

whether these findings are true sequelae of retinal dysfunction. It may be that they are the result of media changes, the effects of the initial trauma to ocular structures, or both.

The goals in surgical management of penetrating IOFB injuries include optimal wound closure, restoration and preservation of ocular anatomy to the extent possible, prevention of secondary infection, and, in most cases, removal of the IOFB. Management of retained IOFBs was revolutionized in 1879 by the development of the Hirschberg hand-held electromagnet; its inventor used it to treat more than 100 patients. A landmark article29 published in 1894 compared Hirschberg’s series with another large series of electromagnetic IOFB extractions in 66 patients. Both series demonstrated excellent visual outcomes in nearly all anterior segment cases and outstanding results in 30% of posterior segment cases.

Some of the lessons learned nearly 100 years ago are still valid today:

•localize the metal as well as possible,

•remove metallic IOFBs early, and

•choose the extraction site and technique that minimize vitreous traction and collateral damage.

Modern advances in the management of these cases include the following:

•diagnostic imaging modalities that have improved IOFB localization,

•advent of vitreous surgery combined with wide-field intraoperative viewing systems,

•surgical instrumentation,

•improved magnets, and

•development and use of antibiotics to prevent and treat infections.

Results of modern vitreous surgery are such that approximately 33% of posterior segment IOFB cases recover visual acuity of 20/40 or better, 67% recover 20/200 or better, and 75% have ambulatory vision of 5/200 or better.5,30–33 These results compare favorably with those pertaining to cases of penetrating ocular trauma without IOFBs. Discussions of current surgical techniques are found elsewhere in this textbook.

Prevention of metallosis is rarely a significant issue in the early, or primary, surgical management

of ocular trauma. The only true indication for early removal of a metallic IOFB as part of the primary surgical procedure is when the object contains more than 85% copper or if there is a high probability of infection. Failure to intervene promptly in such cases is associated with a high risk of endophthalmitis and phthisis.3,24 In all other forms of metallosis, the onset of clinical findings and toxicity generally requires at least several months and may be fully reversible even after delayed surgical intervention. Therefore, there is seldom an urgent indication to remove the IOFB.

The decision of when and whether to remove a metallic IOFB often becomes a side issue in the larger picture of managing ocular trauma. More times than not, removal of the IOFB is incorporated into the vitreoretinal surgery for treating more pressing indications, including

•the presence of a retinal tear or detachment,

•dense vitreous hemorrhage,

•prominent vitreous wicks following the path of an IOFB,

•significant lens disruption, and

•infection.

In the absence of other indications for surgery, determining when and if an IOFB should be removed assumes greater relevance. Inert IOFBs, particularly if they are small and not associated with other indications for surgery, may be reasonable to observe. Reactive metals, such as iron and copper alloys, however, deserve further consideration.

Siderosis

In general, there is seldom any dispute with the recommendation that all ferromagnetic IOFBs be removed to prevent the slow but relentless deterioration in visual function that occurs with siderosis. However, in certain circumstances, surgery might increase the risk of a poor visual outcome (eg, a deeply embedded IOFB in the posterior wall of the globe, or if the patient is reluctant to undergo a procedure). In one case series3 of 84 eyes harboring iron-containing IOFBs, surgery was not performed

in 8 eyes. When surgery is deferred for whatever reasons, observation for signs of siderosis onset and progression should be undertaken. The fact that the retinal changes affect the peripheral fundus before evolving to the macula enables the military ophthalmologist to monitor the patient with an added degree of comfort. Serial ERGs can be very useful in these circumstances. When reductions in b-wave amplitudes approach 50% of baseline, the option for surgery can be considered before further toxicity results in irreversible damage.

Chalcosis

In contrast to siderosis, no consensus exists around the timing and indications for surgery to remove copper-containing IOFBs, largely because the clinical course of chalcosis is more benign and selflimiting than it is for siderosis. Those who historically have favored a conservative approach recommend observation to determine if and when significant toxicity develops, usually in the form of vitreous opacification, advanced macular toxicity, or both.

Reports in the literature support the viewpoint that surgical intervention can be delayed in selected cases and may not always be necessary. In the case

Metallosis Bulbi

series25 of 10 patients referred to previously, 7 patients maintained visual acuity of 20/40 or better for many years—even in the presence of sunflower cataracts and early maculopathy. Furthermore, case reports28,34 have documented complete resolution of the clinical findings when the IOFB is either removed surgically or extrudes spontaneously as long as 15 years after the initial trauma.

With the advent of modern vitreoretinal surgical techniques, the ability to successfully intervene in IOFB cases and minimize iatrogenic complications has shifted current opinion more in favor of earlier surgical management—even before signs of chalcosis develop. Advocates35 of surgical extraction of copper IOFBs refer to the same 10 patients25 who were followed for up to 29 years and point out that only 2 had final visual acuity of 20/20. Furthermore, 6 of the 8 who had ERG testing demonstrated some degree of abnormality, and all 10 had vitreous degeneration to some extent. The authors35 conclude that chalcosis is not completely benign and that it is not possible to accurately predict which cases will do well without intervention or for how long. Therefore, surgery is an appropriate consideration even when there are no other pressing indications for pars plana vitrectomy.

Metallosis bulbi is the name of the condition in which retained metallic IOFBs damage ocular structures; the intraocular changes evolve slowly over months to years. Metallic FBs interact with surrounding tissues to undergo ionization, which is followed by distribution and uptake of liberated ions in various parts of the eye. Toxic effects of the ions result in characteristic clinical findings.

The two most common metals involved in ocular trauma are iron and copper. Iron-containing FBs cause a form of metallosis known as siderosis, and copper-containing FBs cause chalcosis. When a penetrating FB contains more than 85% copper, an acute and suppurative sterile endophthalmitis develops. The clinical findings most commonly seen in siderosis are

•iris heterochromia, with the affected eye having a rust-brown discoloration,

•diffuse cataract,

•RPE degeneration affecting the peripheral retina in the early stages before progressing to the posterior pole, and

•vitreous opacification.

Chalcosis, on the other hand, is characterized by

•the Kayser-Fleischer ring,

•iris heterochromia, with the affected eye having a greenish discoloration,

•a pathognomonic sunflower cataract,

•refractile precipitates in the macular region, and

•vitreous opacification.

Diagnostic modalities that are helpful in detecting metallic FBs include plain film radiography, CT scanning, ultrasonography, and electroretinograms. Electroretinograms often demonstrate reduction in b-wave amplitudes even before clinical signs become apparent. In general, the adverse affects on visual function are more severe in siderosis than chalcosis.

Unless the inciting FB is removed in siderosis, there will be progressive visual deterioration with loss of most vision. In chalcosis, in contrast, relatively good visual acuity may be preserved even in the presence of cataract and macular toxicity. The reason for the difference in prognosis relates to

Ophthalmic Care of the Combat Casualty

pathophysiology: siderosis is associated with deposition of iron ions intracellularly, whereas chalcosis results in copper ion deposition in basement membranes. Damage to ocular structures is far more extensive when the toxic products accumulate intracellularly.

Management of retained IOFBs must be considered within the context of other issues pertinent to surgical decision making. With the rare exception of copper-containing objects that are more than 85% pure, there is no need to incorporate removal of the

FB in conjunction with primary wound closure. Very often, secondary surgical procedures are indicated in trauma cases, and removal of FBs is performed at that time. In the absence of any other indications for vitreoretinal surgery, inert IOFBs can be observed, but metallic iron and copper-contain- ing objects should be removed. The early findings in metallosis may be reversible if the IOFB is removed prior to a 50% reduction in electroretinogram amplitudes, after which the damage may be permanent.

One of the most feared conditions in ophthalmology is sympathetic ophthalmia (SO), a condition in which, after one eye is injured, inflammation threatens blindness in both. Sir Stewart Duke-Elder probably gave the single most comprehensive description of this disease in 1966:

Sympathetic ophthalmitis is a specific bilateral inflammation of the entire uveal tract of unknown etiology, characterized clinically by an insidious onset and a progressive course with exacerbations, and pathologically by a nodular or diffuse infiltration of the uveal tract with lymphocytes and epithelioid cells; it almost invariably follows a perforating wound involving uveal tissue.1(pp558–559)

SO, also known as sympathetic uveitis, is a rare, bilateral, granulomatous panuveitis that occurs after a penetrating injury to an eye. Following injury to an eye—a result of either surgery or accident— a variable period of time passes before a sightthreatening inflammation develops in both eyes. The injured eye is referred to as the exciting eye and the fellow eye as the sympathizing eye. The fact that injury to one eye can result in blindness of both has made SO of enormous concern to ophthalmologists. And because the highest recorded instances of this disease follow combat wounds, SO is of particular interest to military ophthalmic surgeons.

The concept of sympathetic inflammation is an ancient one; probably the first reference in the literature was in a note from Agathias in the anthology compiled from Constantius Cephalis (1000 CE [common era]): “the right eye when diseased often gives its suffering to the left.”1(p560) The clinical disease was known to Hippocrates, and is also found in an old German textbook of ophthalmology.1–3 Bartisch (1583) remarked that when one eye is injured “the other good eye is besides also in great danger.”1(p561)

The modern history of the disease commences with the comprehensive clinical description of Mackenzie in 1840, who first termed the disease “sympathetic ophthalmia.”4 His report was supplemented 65 years later by the classic histopathological findings described by Fuchs.5 In 1910, Elschnig was the first to propose the concept that SO was an autoimmune inflammatory disorder, possibly in response to uveal antigens.6 Two well-known individuals were almost certainly victims of SO:

eye; eventually, “sympathetic ophthalmia overtook his other eye, leaving him totally blind amid his forties.”8

Interestingly, SO was a condition well-known to veterinarians. Wardrop9 drew attention to this fact in 1818:

It is known among some farriers, that, if the eye first affected with this disease suppurates and sinks into the orbit, the disease does not attack the other eye, or subsides if it has commenced in it. Thus they have adopted a practice of destroying altogether the diseased eye, in order to save the other which is crudely done by putting lime between the eyelids, or thrusting a nail into the cavity of the eyeball, so as to excite violent inflammation and suppuration.9(p139)

The concept of inducing suppurative inflammation in an injured eye as a method of protecting the fellow eye became an accepted procedure in the treatment of human disease. Pre-Listerian surgeons

tor of the Braille alphabet and teacher of the blind, experienced a gradual loss of vision in the other eye.7

•As a child, James Thurber, the American author and humorist, sustained a severe eye injury caused by an arrow during a game of William Tell, leaving him blind in one

it, believing that the purulent infection destroyed the factors responsible for the condition or prevented infection passing up the optic nerve by sealing the lymph spaces.1 Prichard in 1851 was the first to practice enucleation as a therapeutic measure.1 To this day, early removal of the injured eye remains the only sure way to prevent SO.

Most cases of SO accompany perforating injuries of the globe in which uveal tissue, especially the cili-

ary body, is traumatized. Incarceration of uveal tissue has been a feature of nearly all cases (Figure 16-1).

Fig. 16-1. An example of a penetrating eye injury from the Vietnam War. Note the dark uveal tissue emanating from the scleral laceration temporally. It is the exposure of uveal tissue to the conjunctival lymphatic system that is believed to be a major factor in the development of sympathetic ophthalmia. Photograph: Courtesy of Francis G. La Piana, MD, Colonel, Medical Corps, US Army (Ret), Ashton, Maryland.

Accidental wounds now account for about 65% of cases, and another 25% follow surgical wounds.10 In 1972, Liddy and Stuart11 reported an incidence of 0.19% following penetrating injury and 0.007% following intraocular surgery. SO occurs more often in children because of the high risk of accidental trauma. Elderly patients also appear to be at an increased risk of the disease because of the greater frequency of intraocular surgery in the aged. The disease does not appear to have a predilection for any race or for either gender, except that its incidence mirrors the increased incidence of ocular trauma in males.

The most common surgical procedures leading to SO include cataract extraction (particularly when complicated), iris surgery (including iridectomy), retinal detachment repair, and vitreoretinal sur- gery.7,12–14 Surgical procedures complicated by the incarceration of the iris or the lens capsule in the wound are particularly prone to develop the condition. Other penetrating surgical procedures re-

Sympathetic Ophthalmia

ported to have resulted in SO include paracentesis, cyclodialysis, and keratectomy, and the risk of SO increases when these surgical procedures are accompanied or followed by additional operations, particularly in the posterior segment of the eye.15 The incidence of postvitrectomy SO has been estimated at 0.01%.16 SO may occur after evisceration, probably as a result of remaining uveal tissue in the scleral emissary channels.17

Only very rarely has SO been diagnosed in cases where there was no perforating wound of the eye, and in many of these cases, the possibility of an occult globe rupture cannot be completely excluded. However, SO has been reported18 following laser cyclocoagulation without apparent globe rupture. Occasionally, the disorder follows perforating corneal ulcers, ocular contusion without rupture of the globe, and intraocular malignancies.19–21 SO has been diagnosed months after helium ion irradiation of a choroidal melanoma; however, a clinically inapparent scleral scar was detected on histopathological examination, possibly indicating an occult scleral rupture.22

The highest recorded incidences of SO have occurred during military conflict. In the American Civil War (1861–1865), 16% of all ocular injuries reportedly led to the development of SO. In the Franco–Prussian War (1870–1871), the reported prevalence of SO after ocular injuries was 55.5% among the Germans and 50% among the French. The disease was still relatively common in the Russo–Japanese War (1904–1905), during which it complicated 5% of eye injuries. In contrast, only rare cases of SO were reported in World Wars I and II, and none were reported in the Korean, Vietnam, and Persian Gulf wars.1,3 Some of the earlier figures must be viewed with some skepticism: in the older literature in particular, SO probably was often confused with other forms of uveitis, and there were few, if any, specialized ophthalmologists among physicians in most wars before this century. Nevertheless, it is interesting and says much for the advances in eye care in the theater of operations that there has been such a dramatic decrease in the incidence of SO in the past century.

SO begins after a latent period following an injury to the eye. In general, 65% of SO cases occur 2 weeks to 2 months after injury, and 90% occur within the first year.3,7 However, SO has been reported as early as 5 days after injury and as late as 66 years.1,7 These figures become clinically important in the prevention of SO. Because the only known prevention is enucleation of the injured eye

prior to the onset of the disorder, obviously such enucleation must be performed early. It is generally agreed that enucleation of an irreparably damaged eye should occur within 2 weeks of injury. Furthermore, although it may be assumed that the risk of SO is extremely small after 3 months, it may never reach zero. Any patient who has sustained a penetrating ocular injury should be considered to

Fig. 16-2. An eye with sympathetic ophthalmia demonstrating the “mutton-fat” keratic precipitates characteristic of granulomatous intraocular inflammation. Scarring from the original injury is present in the superior cornea. Photograph: Courtesy of G. Foulks, MD, Chairman, Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pa.

be at lifelong risk, albeit very small, for the development of this disease.

The diagnosis, especially the early diagnosis, of SO is one of the most important in ophthalmology because prompt and aggressive therapy is required to save vision. The presenting symptoms of the disease include changes in accommodative amplitude, photophobia, and epiphora. Early signs on clinical examination include a low-grade, persistent uveitis associated with granulomatous (“mutton-fat”) or small, white keratic precipitates (Figure 16-2). A diffuse thickening of the iris or iris nodules similar to that seen in sarcoidosis sometimes occurs. Posteriorly, small, yellow-white chorioretinal lesions (Dalen-Fuchs nodules), vitreous cells and haze, choroidal infiltration and thickening, retinal vascular sheathing, and disk edema may be seen. A similar clinical picture develops in the exciting eye and both eyes may proceed to blindness (Figure 16-3).

The presence of Dalen-Fuchs nodules is among the most classic findings in SO, so classic that they were once considered pathognomonic for the disorder. These nodules may occur anywhere in the fundus but are more common in the mid periphery.3,23 They are yellowish white lesions, typically 60 to 700 m (microns) in diameter, found in the subretinal space in at least one third of cases (Figure 16-4).24 Dalen-Fuchs nodules are no longer considered pathognomonic for SO, as they have also been reported in other cases of granulomatous uveitis, such as sarcoidosis, tuberculosis, and the Vogt-Koyanagi- Harada syndrome (VKH).24 Often, microscopic

Fig. 16-3. Severe, bilateral granulomatous inflammation leading to loss of vision in both eyes. Note the shrunken appearance of the right eye indicating early phthisical changes. Photograph: Courtesy of G. Foulks, MD, Chairman, Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pa.

breaks occur in Bruch’s membrane underneath the nodules.25,26 These defects in Bruch’s membrane may lead to the rare development of subretinal neovascularization.27,28

Systemic findings in SO are uncommon but possible. Vitiligo, poliosis, alopecia, dysacusis, and meningeal irritation—findings more commonly reported in the VKH syndrome—may be noted.3,29 An

Fig. 16-4. The fundus of the eye of a patient with sympathetic ophthalmia. Note the characteristic yellowish white Dalen-Fuchs nodules in the mid periphery. These granulomatous lesions are found in at least one third of cases. Photograph: Courtesy of G. Foulks, MD, Chairman, Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pa.

increased number of cells (mostly lymphocytes) in the cerebrospinal fluid can also be infrequently observed.15 These similarities with the VKH syndrome suggest a possible relationship between the two diseases.

Fluorescein angiography seldom is necessary to establish the diagnosis of SO. There appear to be two types of abnormal fluorescence. The most frequently reported type is similar to that usually seen in VKH and consists of multiple sites of choroidal leakage with late coalescence of dye under serous retinal detachments. The sites of choroidal leakage correspond to the Dalen-Fuchs nodules observed clinically. The second, less-common angiographic appearance is similar to that seen in a number of other causes of posterior uveitis, such as acute pos-

Sympathetic Ophthalmia

terior multifocal placoid pigment epitheliopathy. This form demonstrates lesions that (1) block the background choroidal fluorescence during the early phases and (2) stain late.3,15,26,30

SO runs a chronic course, with a marked tendency toward relapses, and the disease may culminate in a phthisical eye (or eyes) and blindness. Before the advent of corticosteroid therapy, the visual prognosis was extremely poor, with approximately 70% of affected eyes becoming permanently blind.31 The more severe the inflammation, the poorer the prognosis; the earlier the diagnosis and more intensive the therapy, the better the outlook. Complications, including cataract, secondary glaucoma, exudative retinal detachment, choroidal scarring, and optic atrophy, are common in long-standing cases.

The histopathological findings in SO, first described by Fuchs in 1905, consist of a diffuse, granulomatous uveitis with a massive lymphocytic infiltration and nests of macrophages, epithelioid cells, and multinucleated giant cells in both the exciting and the sympathizing eyes (Figures 16-5 and 16-6).5 The inflammation is nonnecrotizing, and the epithelioid cells are often seen engulfing melanin pigment. The exciting eye differs from the sympathiz-

ing eye only by the evidence of and complications stemming from the preceding injury or surgical procedure. Nodules containing macrophages, epithelioid cells, and retinal pigment epithelial cells frequently occur between Bruch’s membrane and the retinal pigment epithelium (ie, Dalen-Fuchs nodules; these are discussed in greater detail below). Eosinophils may be present in the uvea, especially in early cases.7,32 The inflammatory process

Fig. 16-5. This low-power photomicrograph demonstrates the diffuse uveal thickening secondary to inflammatory cells in a case of sympathetic ophthalmia (hematoxylin-eosin stain, original magnification x 1).

Fig. 16-6. Higher magnification of the uveal infiltrate demonstrating a chronic, granulomatous inflammation consisting of lymphocytes, epithelioid cells, and multinucleated giant cells. (hematoxylin-eosin stain, original magnification x 400).