Ординатура / Офтальмология / Английские материалы / Tumors of the Eye and Ocular Adnexa_Char_2001

210 TUMORS OF THE EYE AND OCULAR ADNEXA

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Figure 9–35. A, Unusual ring iris-ciliary body ring melanoma. Clinically, this tumor involved approximately 100° of the angle. B, Fine-needle biopsy demonstrates melanoma cells 180° from the pigmented lesion shown in Figure 9–35A.

FIgure 9–36. Increased pigmentation and pressure without a mass. Trabeculectomy did not control intraocular pressure. On referral, the FNAB was positive for melanoma.

Figure 9–37. Large iridectomy for iris melanoma; the patient remains 20/20 5 years after surgery. Some of these patients prefer a cosmetic contact lens to create an artificial pupil.

Larger lesions (> 5 clock-hours) are usually not amenable to surgical resection; if glaucoma becomes intractable to medical therapy and the eye is painful, enucleation is performed.

Laser therapy has been used to treat local recurrences but has not been used in enough patients to evaluate its efficacy for iris melanoma.76 In a few patients we treated many years ago, unacceptable complications were noted. There is also a paucity of data regarding photochemotherapy of anterior segment melanomas, using hematoporphyrin-derivative dyes; a number of failures have been reported.77 A few relatively small iris tumors have been treated with photodynamic therapy.78 In one report, it appeared that those cases could have been treated surgically with probably no greater complications.

Enucleation is usually recommended for iris ring melanomas with increased pressure and for growing iris melanomas that involve over 60 percent of the circumference of the globe. We have reluctantly followed up a few patients who refused treatment with growing iris melanomas that have eventually spread to involve the entire angle circumference. In one case, after 40 years of follow-up, the lesion grew from 1 to 12 clock-hours with retention of good vision (Figure 9–38). Others have reported similar results.79 Initially, this patient refused all therapy; eventually the eye was removed because of uncontrolled glaucoma. The patient lived another 5 years and later died of unrelated causes.

Anterior Segment Metastatic Tumor Therapy

The treatment of anterior uveal metastatic tumors is similar to the management of posterior uveal metastatic tumors. If chemotherapy is indicated for management of systemic metastases, an excellent effect often will be observed on the intraocular tumor.80 Radiation as described for posterior uveal tumors is often effective. At < 30 Gy of photon irradiation, we have usually not seen major posterior segment complications.53,81

Juvenile Xanthogranuloma

Many JXG lesions of either the iris or, less commonly, the ciliary body, will spontaneously regress,

Figure 9–38. Forty years previously this was a 1-clock-hour lesion. It grew in time to involve the entire iris but pressured vision remained good for many years. Melanoma was confirmed histologically 5 years later when the eye became painful and was removed.

often after one or two episodes of bleeding. When lesions are large or have produced either serial bleeds or glaucoma, intervention is necessary. Often JXG can be managed with a short course of high-dose systemic steroids.11 Alternatively, treatment with 2 to 6 Gy of relatively low-dose photon radiation will control these tumors.14 On those patients whose lesions fail to respond to either steroids or radiation, iridectomy or iridocyclectomy can be performed.

DIAGNOSIS OF CILIARY BODY MELANOMA

Choroidal or choroidal-ciliary body melanomas that involve ocular structures anterior to the equator of the globe carry a worse prognosis than those that do not. The prognosis for patients with an isolated ciliary body melanoma is uncertain.82 In recent studies, conflicting reports on the effect of ciliary body involvement in melanoma-related prognosis were presented.83 As discussed in Chapter 5, studies have shown that there are more consistent genomic changes (monosomy of chromosome 3) in ciliochoroidal, compared with posterior, uveal melanomas; however, the etiology and the importance of those genetic alterations remain to be defined.

The differential diagnosis of ciliary body tumors is more concise than that for choroidal tumefactions; however, there is probably a higher incidence of inaccurate diagnoses in tumors in this intraocular location.84 Peripheral melanocytomas (which are most commonly jet-black), lymphoid tumors, leiomyoma (Figure 9–39) epithelial downgrowth with a cystic configuration, neurilemmoma, rarely

Figure 9–39. A growing benign iris-ciliary body leiomyoma that simulated a melanoma.

metastatic tumors, leiomyoma, xanthogranuloma, tumors of the ciliary epithelium, hemangiopericytoma, lacrimal gland choristoma, and scleral ectasia with uveal staphyloma (Figure 9–40) can simulate ciliary body melanomas.13,85–100

Mesectodermal leiomyomas can also simulate a ciliary melanoma.101 In Figure 9–41, this tumor just appeared to produce forward bowing of the iris. On undilated examination, it perfectly mimicked an iris pigment cyst. There was tumor growth so that despite the benign appearance of the FNAB, we resected it, with a good result.

Ultrasonography is useful in the diagnosis of ciliary body or iris-ciliary body melanomas. The diag-

Figure 9–40. Ciliary body staphyloma simulates a melanoma with extraocular extension.

Figure 9–41. Benign, resected ciliary body mesectodermal leiomyoma.

nostic criteria are similar to those used for choroidal melanomas; however, we have observed some lesions that appeared cystic on ultrasonography (Figure 9–42) that histologically were not cysts.86 Cavitary or cystic melanomas of the ciliary body do occur and can produce large cysts probably due to necrosis or exudation.102,103 If high-frequency ultrasonography is used, up to 54 percent of normal adults may have small cysts, more commonly in the inferior temporal sector.20 In difficult diagnostic cases, FNAB can be used. This procedure is described in Chapters 8 and 15. In some reports, however, all tests can be inaccurate, and benign conditions including neurilemmomas, melanocytomas, and adenomas have been mistakenly treated with enucleation.95,97,101,104 We have not had a false-posi- tive FNAB; although, as previously mentioned, in an almost totally necrotic choroidal melanoma, we recently had one false-negative result.

Tumors of the ciliary epithelium include the following: congenital medulloepithelioma and teratocarcinomas that usually occur in children and adenomas and adenocarcinomas that usually occur in adults.

The majority of medulloepitheliomas arise in childhood, with a median age of 5 years; the oldest reported case is 79-years-old.90 These tumors can present with glaucoma, cataract, pain, a visible mass, leukocoria, or decreased vision.61,91 Often, they are white, gray, or yellow; occasionally, a hemorrhage blackens the tumor. There are no established criteria to separate benign from malignant medulloepitheliomas; in one series, 4 of 37 patients died, all with orbital recurrence.4 An atypical presentation of a

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Figure 9–42. A, Ciliary body melanoma with ultrasonographically apparent cyst. On histologic examination, no cystic lesions were noted. B, Similarly, with high-frequency ultrasonography, there is an apparent cystic component of this iris-ciliary body melanoma. C, In contrast, this shows a solid iris melanoma which had documented growth.

Figure 9–44. Neglected ciliary body medulloepithelioma that presented as an extensive mass and partially necrotic orbital mass.

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As Shields has pointed out, usually, these are dark brown or black. Mostly, they are in the periphery and characteristically produce thinning, but not invasion, of the iris. If they are more in the ciliary body location, they have a regular surface, transmit light, and are highly reflective on ultrasonography.106–108 In one report, a false-positive FNAB was described. As mentioned above, we have resected one of these lesions that had rapid, documented growth and was not clinically differentiated from a melanoma. Pleomorphic adenocarcinomas of the ciliary epithelium have been reported, but they had opaque media with blind eyes, and 9 of 12 eyes were phthisical.109,110 Neurilemmoma of the ciliary body can simulate a melanoma with increased pigmentation, episcleral vessels, and a homogeneous appearance on ultrasonography.13

Shields and colleagues have pointed out that leiomyomas of the cilary body and peripheral choroid have a very typical clinical appearance. They transmit light, unlike melanomas, which block it. These tumors have been reported only in women. On fluorescein angiography, there is a normal uveal vasculature overlying them.111 On FNAB, we have managed some patients with benign ciliary body lesions that have not grown on serial follow-up, but in whom we have not made a definitive diagnosis even with FNAB (Figure 9–45).

MANAGEMENT OF CILIARY BODY AND IRIS-CILIARY BODY MELANOMAS

General Considerations

There are a number of therapeutic options in the management of ciliary body or iris-ciliary body melanomas. Serial observation, charged particle or radioactive plaque radiation, local resection, and enucleation are indicated in different cases.82,112–114 Small ciliary body or iris-ciliary body melanomas can be safely monitored, if they are < 10 mm in diameter and < 3 mm in thickness. Growing, small anterior uveal melanomas, those that have eroded through the iris root (Figure 9–46), vascular tumors, and lesions > 10 mm in diameter or > 3 mm in thickness should be treated at the time of diagnosis.

The relative efficacy of surgical removal versus irradiation of these tumors is unclear.82,115–117 Irido-

cyclectomy, cyclectomy, cyclochoroidectomy, or iridocyclochoroidectomy has much higher complication rates when melanomas involve > 4 clock-hours of ocular circumference.114–120 As discussed below, this type of surgery is technically challenging, and results vary widely.

There are no prospective, randomized data on resection versus radiation. Given the variability of surgical techniques, it is doubtful that meaningful data could be generated with that approach.

Our impression has been that two groups of patients are better managed with local resection, compared with radiation. In some focal ciliary body tumors that are 2 to 3 clock-hours in circumference, an experienced surgeon can usually remove them with good margins and preserve excellent vision. Unfortunately, most patients do not have small or small growing tumors isolated to the ciliary body that involve < 3 clock-hours of its circumference. In very thick tumors (generally > 7 mm), especially those with a relatively narrow tumor base, surgery is probably a better option than radiation. The rationale for that last statement is that in irradiated patients, independent of tumor location, tumor thickness (especially > 7 mm) is associated with a poorer ocular outcome. As tumors progressively thicken, there is a more than exponential increase in radiationassociated complications. Similarly, our experience with both brachytherapy and charged particles has shown that eyes with very thick ciliochoroidal

Figure 9–45. The FNAB shows a benign ciliary body spindle cell tumor; 5 years later, the mass is unchanged, and vision remains 20/20.

Figure 9–46. Anterior ciliary body melanoma with erosion through the iris root.

melanomas have over a 35 percent incidence of late enucleations from post-treatment complications, mainly neovascular glaucoma, and that < 20 percent retain good vision.121,122 What has become apparent, however, is that iridocyolochoroidectomies alone are not sufficient, and even with clear surgical margins, patients do better if they have adjunctive radiation, either with particles or a beta-emitting plaque.123

The author has done over 150 choroidectomies, iridocyclectomies, and cyclochoroidectomies. What is uncertain is where the equation shifts toward favoring radiation over surgery or vice versa. Certainly a tumor > 15 mm in largest diameter or one that is relatively thin (< 5 mm height) will do better with radiation. It is technically difficult to resect tumors that involve that much of the ocular area, although we have successfully removed some lesions up to 18 mm in diameter. Similarly, eyes with tumors < 5 mm thick will usually have a lower incidence of complications with radiation, compared with surgical resection. As a general rule, while retinal detachment or increased tumor thickness does not pose added technical problems for the surgeon, tumor diameter > 15 mm, a tumor with retinal invasion and collar-button configuration with invasion through the retina, individual variations of orbital anatomy (ocular proptosis, the shape of the nose), and the posterior tumor edge contiguous with the optic nerve are major factors in complications that have been observed. If a ciliochoroidal tumor has broken through Bruch’s membrane and has invaded the retina, it is often impossible to peel the inner part

of the melanoma off the retina, and part of the tumor unfortunately may be left behind.

Cataract can occur with radiation as well as surgery. An advantage of surgery is that if it is successful, the tumor is removed and there is a lesser incidence of late complications. As discussed later, late recurrences can occur with either type of treatment. Most complications following surgery occur within the first 3 months, while radiation complications continue to develop for years after therapy.

Surgical Resection

Surgical Procedure

The two prevalent techniques for surgical resection of uveal tumors can be divided into (1) those utilizing a full-thickness, en bloc, sclera combined with melanoma resection with placement of an allogeneic corneal or scleral graft, and (2) those in which a 90 percent thickness scleral flap is created, and the tumor and overlying inner sclera are resected.113–125 We prefer the latter approach and think it is technically easier and as effective as the former. Historically, some surgeons treated the peripheral retina (if the tumor did not involve the choroid) with a row of contiguous cryotherapy 6 weeks prior to resection to decrease the likelihood of retinal detachment. While we initially used this approach, in recent years we have stopped it without observing an increased incidence of retinal detachment. The majority of retinal detachments we have had have occurred either from traction away from the area of tumor resection or from a retinal hole created during surgery and would not have been prevented with this approach. Surgery is performed using hypotensive anesthesia if the patient’s cardiovascular status allows it. The use of hypotensive anesthesia decreases bleeding during surgery and simplifies the operation. Unfortunately, the strong technical advantage of hypotensive anesthesia somewhat limits the patients who can be operated on. While one can do an anterior uveal resection without hypotension, we think it is very difficult to get good results for a posterior tumor, and we therefore do not use this treatment in patients who are very old and hypertensive, or have had recent myocardial infarctions or significant cardiovascular disease.

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Historically, a modified Flieringa ring or eyewall basket was sutured to the area of resection. We stopped using those when we started to operate on larger tumors. At present, we only use this type of device when we are forced to operate on a young child with a very small tumor; that is quite rare.

Tumor localization techniques are discussed in Chapter 8. We use a corneal diffuse transilluminator as well as indirect ophthalmoscopy with point-source transillumination to localize the tumor. In addition, we use another type of transilluminator that we can hold against the sclera 180° away from the tumor mass. Using these three techniques we take a surgical marker and outline the tumor diameter on the sclera. As mentioned previously, corneal transillumination alone can produce a falsely increased posterior dimension to the tumor, as a result of a shadowing effect of the mass.

The use of an infusion cannula and vitrectomy equipment is optional. Some surgeons perform a vitrectomy in all cases, and often use silicone oil. We have tended not to do this but have instead only used vitrectomy when we felt it was indicated. If vitrectomy is going to be done, an infusion cannula should be sutured approximately 3.5 mm posterior to the limbus in an area 180° degrees away from the tumor. At that point, we also place diathermy marks at other sites 3.5 mm from the limbus that are away from the tumor for possible placement of a light pipe and vitrectomy instrumentation.

In the surgical resection of uveal melanomas, we create a 90 percent thickness scleral flap. If it is an iris-ciliary body tumor, the incision is started at the limbus and carried posteriorly as shown in Figures 9–47A and B. If the tumor is localized just to the choroid or choroid and posterior ciliary body the incision is started approximately 3 mm anterior to and away from the scleral margins of the neoplasm (see Figure 9–48).

A No. 59 Beaver blade is used to create the scleral flap. The edges of the flap should be at least 2 to 3 mm from the transilluminated edges of the tumor. If the sclera remaining over the tumor is too thin (1 to 5 percent thickness), uveal prolapse occurs and makes the dissection more difficult. If this is a problem over a small area, the site may be glued to provide temporary stability. If the scleral flap is too

thin, poor closure and/or post surgical hypotony may develop.

A triple row of penetrating diathermy is placed in the resected scleral bed, around the circumference of the tumor as shown in Figure 9–47B. The purpose of the diathermy is threefold: (1) it may prevent a retinal detachment after resection of the tumor; (2) diathermy tends to diminish intraocular bleeding from the cut margins of the uvea at the time of resection. This bleeding is also decreased as a result of hypotensive anesthesia; and (3) if the resection is not complete and there is microscopic extension, it is conceivable that the contiguous rows of diathermy will have destroyed remaining tumor cells. It is likely that diathermy, used by many surgeons, has been partially responsible for the low rate of recurrence noted even when there is a microscopic tumor at the edge of resection following an iridocyclectomy.

As discussed below, the author strongly believes that there is marked difference in the shrinkage of the very thin normal surrounding uveal tissue, compared with the markedly thicker tumor when fixed for histologic sections. As a result, it can often be difficult to be certain if there is sufficient margin between the tumor and the edge of resection even when there is, in fact, a reasonable distance.

After diathermy, but before the tumor is resected, a vitrectomy instrument is placed in the eye, distant from the tumor, and approximately 1 to 1.5 mL of vitreous removed. A diamond knife is used to incise the remaining scleral fibers surrounding the tumor, starting posteriorly and going forward. If the iris is involved, corneal-scleral scissors are used at the limbus to open the wound. Using angled Vannas scissors, the iris portion of the tumor is excised. Using forceps to grasp scleral tissue overlying the tumor, corneal-scleral scissors are used (see Figure 9–47B) to remove the tumor and overlying sclera. If pointsource bleeding is noted, a unipolar wet-field cautery is used for hemostasis. Usually, the tumor may be removed en bloc without loss of vitreous. In very thick tumors, often the apex of the lesion must be gently teased and slowly elevated from the retina and vitreous. We have experimented using a laserscalpel or a CO2 laser mounted on the microscope for this portion of the resection, but the author remains unconvinced that these techniques are an

improvement. Preplaced 8-0 vicryl sutures at the corners of the incision (see Figure 9–47B) are tied. The scleral portion of the incision is closed with interrupted 8-0 vicryl sutures, while the corneal portion is closed with interrupted 10-0 nylon. Either the infusion port is used to refill the vitreous cavity for more posterior resections or for an iridocyclectomy, fluid balanced salt solution (BSS) is introduced through the limbal corneal incision. The suture lines are tested for a tight closure.

Postresection vitrectomy is usually not indicated, unless there is vitreous loss, a retinal detachment, or extensive hemorrhage. There is moderate bleeding at the time of resection in most cases, but usually this

does not require intervention. If there is significant vitreous loss at surgery, a modified open-sky vitrectomy through the iridocyclectomy wound is performed to remove vitreous that is adherent to the wound edges. The eye is closed, and a standard, three-port vitrectomy is performed; if the lens is clear, it is not removed.

Results and Complications of Resection

The incidence of ocular complications is highest when larger-diameter (> 15 mm) ciliary body tumors and very large posterior choroidal tumors are resected. Immediate complications of surgery

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Figure 9–48. Schematic scleral incision for posterior tumors distal to the iris and anterior ciliary body. Scleral incisions are made approximately 3 mm from the tumor margin that was outlined by transillumination and marking pen, on the scleral surface.

include vitreous loss, vitreous hemorrhage, expulsive choroidal hemorrhage, retinal detachment, and intraocular infection. We have had 4 expulsive hemorrhages in over 150 cyclectomies or choriocyclectomies. Almost uniformly, especially if a choroidectomy is performed, an area of peripheral diffuse or focal, hemorrhagic choroidal detachment develops; this slowly resorbs over the first postoperative month. Sometimes, intraocular pressure is transiently elevated and requires a few days antiglaucoma treatment with timolol maleate (Timoptic), carbonic anhydrase inhibitors, or xalatan drops. Hypotony in the immediate postoperative period is associated with a poorer prognosis for retention of the eye. A topical steroid is used for the first 2 weeks to minimize inflammation; this drug may also increase intraocular presssure. Figure 9–49A and B shows an eye with large iris-ciliary body melanoma 2 years after successful resection, but with recurrent tumor (despite negative margins) 5 years later.

Figures 9–50 to 9–52A to C show several cases of large tumors that were resected with reasonable long-term outcome. All these lesions are large and would probably have had significant morbidity had radiation been used. On large tumors that involved the choroid, we routinely reinforced the vitreous base with a relatively high 42 band. The case shown

in Figures 9–52A and B initially did well and then had a small recurrence (Figure 9–52C) 4 years later. This tumor was then treated with proton radiation.

The most common late complications after surgical resection include tumor recurrence, retinal detachment, and cystoid macular edema. Cystoid macular edema most commonly occurs following resection of a large tumor with vitreous loss, or persistent intraocular inflammation. This complication is quite difficult to manage, and most patients do not regain better than 20/200 vision.

In the author’s experience, late tumor recurrence has been less common, if the surgical margins are clear, if penetrating diathermy was used around the circumference of the tumor, and if postoperative irradiation is given.123 In one series, almost 40 percent of iridocyclectomy specimens had tumor at the surgical margins, and the majority did not recur.126 In another series, incomplete resections, as evidenced by posi-

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Figure 9–49. A, Postoperative appearance of the eye 2 years after resection of a large iris-ciliary body melanoma with good vision. B, Patient from Figure 9–49A, 5 years later with recurrent tumor despite clear histologic margins.

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Figure 9–50. A, Large ciliochoroidal melanoma (9.5 mm thick) noted after cataract extraction. B, Resection of tumor resulted in 20/40 vision. Patient is alive and well 9 years later.

tive margins, was not a major prognostic factor.119 Given the small specimen size, frozen sections have not been reliable to ascertain the adequacy of tumor margins. If only microscopic extension is noted on permanent histologic sections and there is no clinical evidence of tumor, these eyes irradiated postoperatively are monitored without further intervention. As discussed earlier, we hypothesize that many such cases have been cured by the surrounding diathermy. If there is gross tumor noted on both histologic and clinical examinations after surgery, the eye should be removed or treated with curative radiation with a radioactive plaque or charged particle beam, depending on the amount of residual or recurrent tumor.119 Data presented by Damato and colleagues is intriguing regarding the beneficial effects of adjuvant radioactive plaques. In their experience, there was significantly less late recurrence when patients received adjuvant plaques; however, it is impossible

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Figure 9–51. A and B, Large ciliochoroidal melanoma prior to and after resection with 20/25 vision.