In ophthalmic surgery, biopsy has been used in lesions involving adnexal, orbital, anterior, and posterior segment. Surgical specimens of the eyelid and conjunctiva are easily obtained with minimal surgical trauma. Anterior segment lesions are readily accessible, and excisional biopsies of iris lesions are accomplished by open iridectomy.

The more posterior uveal lesions, including those of the ciliary body and choroid, are not as accessible to excisional, incisional, or fine-needle biopsy. Specialized techniques, surgical skill, and experience are often necessary to achieve the desired goals without complications.^1,2 One study indicated that in specialized oncology units, 0.5% to 1% of eyes enucleated for suspicious malignant tumors may be nonmalignant on histopathology.³ The percentage may be higher in other centers. Biopsy has a diagnostic role in avoiding unnecessary globe removals. Newer refinements in surgical technique and instrumentation allow skilled ophthalmic surgeons to perform biopsy in posterior uveal lesions.

Posterior uveal biopsy may be achieved by fine-needle aspiration techniques, either under direct visualization or ultrasonographic control.⁴ Vitreous biopsy may be performed with needle aspiration⁵ or, preferably, with cutting vitrectomy instruments to reduce the vitreous-retinal traction and risk of retinal detachment. These forms of biopsy provide small biopsy samples without damage to histologic architecture. Large-bore needles have been used to gather cellular cores; however, they also can cause more vascular and tissue trauma. Clinical diagnostic difficulties with amelanotic malignant melanoma, infections,^6,7 inflammation,⁸ and metastatic tumors^9–11 represent the majority of cases in which fine-needle aspiration biopsy has been used.

The biopsy techniques of sclerochorioretinectomy of Peyman^12,13 and partial lamellar sclerouvectomy of Shields^l4 are the most common methods of combined local resection and excisional biopsy. There are many potential problems with extensive surgery, including vitreous hemorrhage, cataract, retinal detachment, suprachoroidal hemorrhage, and ocular hypotony. However, the combined biopsy and resection offers histologic confirmation and definitive management. The eye can often tolerate extensive surgery and maintain surprisingly good vision if vital structures are not involved. Eyes with lost visual potential, severe glaucoma, or pain should probably be removed.¹⁵ Newer methods of internal resection for malignant melanoma are currently under investigation and may eventually offer another treatment in our surgical armamentarium.^2,16,17

GROWTH OF IRIS MASS

Tumor growth typically is slow and necessitates accurate serial photographic documentation. Pigmentary changes may occur for a number of reasons and should not be considered as evidence of definite growth. There is no evidence that there is a critical size of iris tumor prior to metastasis; however, any lesion greater than 2 clock hours usually involves the angle structures and require larger amounts of resection. Iris lesions closer to the iris root are more likely to involve the ciliary body and angle, necessitating an iridocyclectomy.

Heterochromia may indicate that the tumor more diffusely involves the iris stroma.²² Tumor seeds, spotted over the iris surface, also indicate a more diffuse nature. In certain instances, normal and abnormal iris areas cannot be clinically differentiated, necessitating multiple biopsy sites or a more radical surgical approach.^22,23

IRIS LESIONS

In the last decade, iris biopsy has been used to diagnose iris lymphoma, leprosy, juvenile xanthogranuloma, leukemia, coccidioidomycosis, Lyme disease, and Refsum's disease.^24–29 Lack of tissue diagnosis does not preclude the presence of a neoplasm, even when performed at tertiary centers experienced in ophthalmic oncology.³⁰

TECHNIQUE OF EXCISIONAL BIOPSY

The goal of surgery is to remove the malignant lesion en bloc without contamination and tumor seeding of the remaining tissue.²¹ The surgical approach is similar to extracapsular cataract extraction. Wide shelving of the incision should be avoided to allow adequate iris root exposure and complete excision. Sutures may be preplaced or placed later. A viscoelastic substance is used to protect the lens and the cornea from surgical trauma (Fig. 1A); however, adequate removal is necessary prior to wound closure. With the cornea retracted by the assistant, Barraquer or Vannas scissors are placed radially through the pupil and a cut is made up to the base on either side of the lesion in normal-appearing iris (Fig. 1B). The section of iris is grasped at the pupil margin, and fine scissors, usually curved Vannas scissors, are used to incise through the iris root (Fig. 1C). A similar approach for circumscribed iris lesions has been described by Shields and Shields,^21,31 termed partial lamellar scleroiridectomy.

To achieve histologic orientation, the specimen should be pinned to a tongue depressor or piece of filter paper prior to placing into fixation solution. Fixed in this manner, proper anatomic margins of the tissue are preserved.

PROGNOSIS

The prognosis for vision is generally good in well-defined iris melanomas, providing surgical excision is without complications.²³ Hyphema, corneal decompensation, cataract, and poor intraocular pressure control all can affect outcome. Cataract surgery may be combined with the excision of the iris lesions, but is usually postponed for secondary management. The prognosis for survival in iris melanoma excision is favorable with reported metastasis in less than 4% of patients,³² although more recent reports demonstrate 10% metastatic rates at 20 years.²¹ Rones and Zimmerman¹⁸ reported three deaths from metastases in 125 patients observed for as long as 15 years or more. Diffuse iris melanomas with heavy pigmentation are most likely to metastasize, particularly if nuclei show prominent nucleoli.

INDICATIONS FOR IRIDOCYCLECTOMY

Mass Lesion Growth

The option of observing a ciliary body lesion is determined by its initial status on presentation. Small lesions may be followed for growth if visual functions are intact; however, most melanomas⁴³ and medulloepitheliomas⁴⁴ result in early enucleation because of advanced stages at presentation with cataract, glaucoma, retinal detachment, and sometimes pain.

Small lesions confined to the iris and ciliary body may be successfully resected, usually when they produce symptoms or documented suspicious growth. Ciliary body melanoma often remains hidden and asymptomatic until attaining a large size, which may obstruct the visual axis or produce glaucoma.

Vail³³ noted that iridocyclectomy may be performed with lesions not greater than 4 clock hours, although other authors have stated that lesions from 2.5 to 6 clock hours can be safely excised.^20,33,45,46 Intraoperative and postoperative complications, particularly hypotony, are increased proportionally by the size of the tumor. Whether enucleation would result in better survival statistics than iridocyclectomy in larger melanomas is not known. Complications include seeding of the iris by iris melanoma and tumor recurrence.^47,48 Thorough systemic and ocular examination should reveal no evidence of tumor extension or metastases prior to excision.

TECHNIQUE OF IRIDOCYCLECTOMY

Limbal Flap Approach

A fornix-based conjunctival flap is made to expose sclera in the area of the tumor. An anterior-hinged limbal-scleral flap is raised four-fifths of the scleral thickness at least 3 mm around the tumor (Fig. 2). Diathermy is applied to the remaining scleral bed surrounding the tumor. The anterior chamber is entered, and the flap is elevated to expose iris and tumor (Fig. 3). The tumor is excised starting at the pupil margin, moving posteriorly, and removing the section in one piece. The sector iridectomy is then closed with fine nonresorbable suture and the scleral flap is closed with interrupted sutures (Fig. 4).

T Incision of Stallard

The T incision of Stallard allows larger tumor exposure and excision. A conjunctival flap is opened to expose bare sclera and a Flieringa ring is fixed through episcleral sutures. A T-shaped limbal-scleral incision is then made with a knife and extended with the corneoscleral scissors. Closing sutures may be preplaced. The ciliary body surrounding the lesion is treated with penetrating diathermy (Fig. 5A). With the cornea and scleral flaps reflected, the pupillary margin is grasped and the iris incised radially to the iris root (Fig. 5B). The involved portion is excised with scissors.^49,50

Fig. 5. A. A T-shaped incision is made over the tumor to expose the mass outlined by transillumination. Diathermy is placed around the tumor-free margins. B. The pupillary margin is grasped and the iris incised radially to the iris root. The tumor is excised by grasping the pupil margin with Vannas scissors. C. Curved scleral-limbal incision with trephine of Müller. The area over the tumor is trephined through the cornea and sclera. D. The corneoscleral button is depressed, and the scleral graft is sutured in place. The tumor is then excised with the corneoscleral tissue.

Modifications of this technique, such as eliminating the Flieringa ring or including cataract removal, may be made as necessary. Müller⁴⁵ described a technique using a trephine to replace the overlying corneoscleral tissue over the tumor prior to dissecting the sclera (Fig. 5C). Its advantage is that there is less likelihood of disturbing the tumor mass while excising the tumor (Fig. 5D).

Iridocyclochoroidectomy of Peyman

Iridocyclochoroidectomy of Peyman allows large tumor removal when there is more choroidal involvement posteriorly. After transillumination, localization, and marking on the bare sclera, a Peyman C-shaped cyclectomy basket is sutured in place (Fig. 6A). The scleral flap is fashioned depending on the location of the tumor. A limbal-based scleral flap can be raised with tumors located anteriorly not involving the retina. However, with more posteriorly located tumors that involve the retina, the scleral flap is started at the limbus and dissected posteriorly. A partial-thickness scleral flap is dissected and penetrating diathermy performed around the tumor margins outlined by transillumination (Fig. 6B). The tumor is excised with scissors, using radial iris incisions extending along the diathermy margins (Fig. 6C). The crystalline lens is removed with vitrectomy instruments, cutting all zonular attachments. After suturing the sclera in place with fine nonresorbing sutures (Fig. 6D), a vitrectomy is completed through an opening in the wound, or preferably using a standard pars plana approach. Ocular volume is replaced by intravitreal gas or silicone oil injection. Endolaser retinopexy is used to augment diathermy more posteriorly around the tumor base to ensure chorioretinal adhesion.

The major complications of iridocyclectomy and large excisional biopsy include hemorrhage, vitreous loss, cataract and lens dislocation, and retinal detachment. Many authors have expressed surprise, however, at the small amount of hemorrhage that occurs postoperatively, although hemorrhage is the most common complication. It is likely that the penetrating diathermy encircling the excised ciliary body lesion reduces the risk of hemorrhage.

FINE-NEEDLE ASPIRATION BIOPSY

Ophthalmic fine-needle aspiration biopsy has developed along with the evolution of radioactive plaque therapy and more conservative surgical approaches to enucleation. Cytopathologists have achieved definitive diagnoses based on small cellular samples.^54,55 The method of choice for fine-needle aspiration biopsy is contingent on the existing anatomic state of the eye, the location of the tumor, size of the tumor, and presence of retinal detachment. The anterior uveal lesion may be approached through the cornea-limbus for iris lesions (Fig. 7), or in aphakic eyes, into the more posterior ciliary body lesions (Fig. 8). In the posterior uveal lesion, either a pars plana transvitreal approach may be made (Fig. 9) or a transscleral approach may be adapted in more anterior lesions or in lesions with overlying retinal detachment (Fig. 10). Most surgeons prefer to use a 25-gauge fine needle with a flexible connector to a 10-mL aspiration syringe to minimize movement and surgical trauma during biopsy (Fig. 11). Some surgeons prefer a spinal tap needle with a trocar and cannula⁵⁶; however, many surgeons use a standard long 25-gauge needle. It is felt that the excess movement caused by removing the trocar and attaching a syringe and flexible connector may lead to increased complications.

For anterior segment fine-needle aspiration biopsy, the needle is inserted from the opposite side of the mass under direct visualization of the surgical microscope.⁵⁷ For posterior segment lesions, the transvitreal approach is used, initially making a small partial-thickness 1.5 mm–long sclerotomy with a no. 57 Beaver blade. Only the 25-gauge needle passes through the remaining sclera. Subsequently, the wound is closed with 6-0 or 7-0 Vicryl sutures.

Seeding of tumor cells along the needle tract is thought to be reduced by the transvitreal approach because of the sweeping action of the vitreous.⁴ Tumor cell seeding along the scleral needle tract has been reported with retinoblastoma and has been identified in needle tracts of aspiration biopsy in the enucleated eye harboring melanoma.⁵⁸ The transvitreal approach also allows deep penetration of the tumor by the needle through the overlying retina. This, however, increases the risk of rhegmatogenous retinal detachment (see Fig. 9).

Char and Miller⁵⁹ demonstrated in a retrospective study that fine-needle aspiration biopsy was useful in identifying 9% of lesions that had been presumed to be uveal melanoma on noninvasive testing. They concluded that noninvasive testing was not as accurate as fine-needle aspiration biopsy for smaller lesions. Cohen and colleagues⁶⁰ demonstrated that fine-needle aspiration biopsy had a diagnostic accuracy of 98% for choroidal lesions 4 mm or greater in height, but only 40% for lesions less than 1.99 mm.

INDICATIONS FOR CHOROIDECTOMY

Careful documentation of tumor growth is important before treating small tumors. Diagnostic biopsy is usually reserved for difficult clinical settings in which the diagnosis is in question. A complete diagnostic evaluation, including serial photography, ultrasonography (A-scan and B-scan), magnetic resonance imaging, and intravenous fluorescein angiography should be undertaken.

The maximum size of tumor that can be resected has not been determined. Large choroidal and ciliary body tumors have been resected; if the tumor is located anteriorly and has greater height and a narrow choroidal base, it is easier to remove. Tumors of up to 17 mm have been resected by Peyman.^61,62 Lesions closer to the fovea or the optic nerve may have poor visual and anatomic results if removed by external resection. Postoperative hypotony may be prevented by the use of intravitreal silicone oil and silicone gels.⁶³ Lesions closer than 4 disc diameters to the disc are difficult to remove without significant trauma and may represent cases best approached by an internal resection method.^17,64–66 Tumor location within 1 diameter of the optic disc or fovea is significantly associated with local tumor recurrence following choroidectomy.⁴⁸ The risk of retinal detachment has been reported to range from 9% to 18% following choroidectomy.^67,68

TECHNIQUES OF CHOROIDECTOMY

Trapdoor Approach of Stallard

After a conjunctival peritomy, a Flieringa ring is sutured to the bare sclera. A lamellar-scleral flap (50% to 80% thickness) is dissected in a trapdoor fashion over the tumor area. Penetrating diathermy is applied around the lesion with adequate margins. The lesion is excised with scissors (Fig. 12), leaving the retina intact.

Full-Thickness Eye Wall Resection of Peyman

Preoperatively, the mass lesion is surrounded by rows of heavy photocoagulation, which is performed in two sessions 3 to 4 weeks apart.^69–75 The resection is performed 4 weeks after the final session.⁷³

A conjunctival 360-degree peritomy is carried out, and the tumor is localized by transillumination and diathermy. A Peyman basket is sutured to the globe. A partial-thickness scleral flap is dissected around the lesion. Penetrating diathermy is applied around the tumor in the scleral bed. A pars plana sclerotomy is performed for later vitrectomy and sealed with scleral plugs or temporally sutured (Fig. 13A). The tumor is excised with curved Vannas scissors (Fig. l3B). After the scleral flap has been sutured in place (Fig. 13C), a pars plana vitrectomy is performed to remove any vitreous blood and incarcerated vitreous from the excision site (Fig. 13D). Surgery is performed under hypotensive anesthesia to reduce the risk of hemorrhage.⁷²

Partial Lamellar Sclerouvectomy of Shields

Partial lamellar sclerouvectomy of Shields was modified from Foulds' original technique described in the 1970s.^16,44,64 A scleral flap is made over the tumor site.⁷⁶ The flap is dissected to 80% thickness and opened over the tumor with scissors at one edge. The tumor is lifted with the sclera using fine forceps and bluntly dissected from the retinal tissue with a muscle hook (Fig. 14). An attempt is made to leave the retina and vitreous intact. A surgical margin of 4 mm is outlined around the tumor prior to excision.

Internal Retinochoroidectomy of Peyman

Tumors within one to 2 disc diameters of the optic nerve cannot be easily resected by an external approach. These shortcomings have led to the development of internal excisional and biopsy approaches that may prove useful in management of lesions involving the posterior pole.^65,66,69

The original technique required placement of barrier photocoagulation surrounding the lesion before retinochoroidectomy^65,66; however, the more recent technique of choroidectomy under a retinal flap requires no posterior photocoagulation.²

Three or four pars plana sclerotomies are performed, one reserved for a chandelier light source. Endodiathermy is applied, and a 180-degree arcuate retinotomy is performed to ensure a 1 disc–diameter tumor-free margin (Fig. 15A and B). The retinal flap is dissected and the entire tumor exposed (Fig. 15C). Argon endolaser is applied to the tumor surface and free margins. Tumor and free margins are then dissected and removed. Following tumor removal and complete vitrectomy, the retinal flap is repositioned and an air-fluid exchange is performed. Endolaser is applied to retinotomy edges and the posterior pole (Fig. 15D). Oral aminocaproic acid is begun 24 hours preoperatively and continued for 5 days postoperatively. Hypotensive anesthesia is used during choroidectomy and tumor excision.

RESULTS OF CHOROIDECTOMY

Shields and colleagues¹⁴ reported that the integrity of the globe has remained intact after removal of large ciliary body and choroidal melanomas. Of 95 patients, 26% maintained 20/30 vision after surgery at a mean follow-up of 5 years, and in 74 cases of confirmed melanoma, 91% of patients were alive and well.

In 1984, Peyman and colleagues⁷⁷ also reported success with eye wall biopsy with long-term follow-up. Two deaths from tumor metastases occurred in the 35 patients harboring melanomas. This represents a 5.7% mortality over a mean follow-up period of more than 5 years. The interval from eye wall resection to determination of metastatic disease was 36 and 42 months in the two patients. Two additional patients died of unrelated causes. The remaining 23 eyes retained good cosmesis.⁷⁷ To date, it appears that the postoperative mortality for local resection is not significantly different from mortality after enucleation.^{14–16,64,78} A review of 21 confirmed melanoma patients undergoing internal retinochoroidectomy was reported by Peyman and colleagues.¹⁷ The patients underwent surgery between 1984 and 1991. A total of three patients (14%) died of metastasis at 15 months, 57 months, and 84 months. These data agree with other data presented for external eye wall resection of malignant melanoma that show mortality associated with these techniques does not differ from that of patients treated with enucleation.^15,16,44,77 Longer follow-up (mean 40.1 months) on patients undergoing internal resection of posterior uveal melanomas demonstrated a combined metastatic and mortality rate of 9.4%, one local recurrence, and a 9% retinal detachment rate.⁷⁹ Visual acuity of 6/60 or better was maintained by 31.2% of patients.

Diagnostic biopsy specimens require special attention to ensure that the sample is properly handled. Pinning the sample flat or using cyanoacrylate glue to firm the edges allows proper orientation of the soft sample.¹ Biopsy has been useful in diagnosis of early reported cases of Pneumocystis carinii choroiditis,⁸⁰ metastatic lesions, and amelanotic choroidal lesions. Expanding roles for uveal biopsy may develop as surgical techniques improve and limitations of noninvasive techniques are recognized.

Eye wall biopsy (Fig. 16) has been successfully used in nine patients to diagnose retinal and choroidal disease. Long-term follow-up of these patients has shown no untoward effects from such surgery.⁷⁰ A modified scleral flap version of this technique has been advocated by Constable and coworkers.⁷²

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