If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
To perform micro-incision, trans-iridal, aspiration-cutter-assisted biopsy for ciliary body tumours.
Retrospective, nonrandomized, observational, interventional case series.
Five consecutive patients undergoing ciliary body tumour biopsy were clinically diagnosed using slit-lamp photography, gonioscopy, high-frequency ultrasound imaging, and systemic radiographic staging. A 1–2 mm clear cornea incision was placed opposite to the central clock hour of the ciliary body tumour. Viscoelastic was infused into the anterior chamber for stabilization and endothelial protection. Then, a 27-gauge aspiration cutter was used to make an iridotomy at the iris root and then extend through the iris into the tumour. Biopsy was performed using mechanical cutting starting at 300 cuts per minute and aspiration at 600 mm Hg. After withdrawal of the cutter from the eye, the effluent tube was flushed into a 3 cc syringe, inspected for specimen under the operating microscope and sent for pathology. Multiple biopsies were performed on each patient. Viscoelastic was removed and Seidel examination of the corneal wound performed.
Five eyes were biopsied. A mean 3.6 passes were used to obtain tumour tissue. Tumour cells and tissue were obtained in all cases. Cytologic, histopathologic, and immuno-histochemical analysis were performed (100%, n = 5/5). Diagnoses included melanoma (60%, n = 3/5), melanocytoma (20%, n = 1/5), and leiomyoma (20%, n = 1/5). Transient postoperative hyphemas cleared within 1 week (80%, n = 4/5). No secondary glaucoma, infection, or cataracts were noted.
Aspiration-cutter biopsy through the iris root provided a minimally invasive, safe method for obtaining ciliary body tissue for cytology, histopathology, and immunohistochemical analysis.
Réaliser une biopsie micro-incisionnelle trans-iridienne par aspiration-section des tumeurs du corps ciliaire.
Étude rétrospective d'observation et d'intervention non randomisée portant sur une série de cas.
Cinq patients consécutifs devant subir une biopsie en raison d'une tumeur du corps ciliaire ont fait l'objet d'un diagnostic clinique reposant sur les techniques suivantes: photographie à la lampe à fente, gonioscopie, imagerie ultrasonore haute fréquence et stadification radiographique systémique. Une incision de 1–2 mm en cornée claire a été réalisée du côté opposé à l'heure de l'horloge du centre de la tumeur du corps ciliaire. On a alors procédé à l'injection d'un produit viscoélastique dans la chambre antérieure pour obtenir une stabilisation et pour protéger l'endothélium. Par la suite, un appareil à aspiration-section de calibre 27 a été utilise pour réaliser une iridotomie au niveau de la racine de l'iris, pour ensuite traverser l'iris et atteindre la tumeur. La biopsie a été faite aux réglages suivants: coupe mécanique à 300 coupes par minute (minimum) et aspiration à 600 mm Hg. Une fois le dispositif de coupe retiré de l’œil, le contenu du tube d'effluents a été transféré dans une seringue de 3 cc, examiné au microscope chirurgical pour s'assurer de la présence de cellules tumorales et envoyé au laboratoire d'anatomopathologie. Plusieurs biopsies ont été réalisées chez chaque patient. Le produit viscoélastique a été retiré, et on a soumis la lésion cornéenne à un test de Seidel.
Cinq yeux ont ainsi fait l'objet d'une biopsie. On a dû réaliser en moyenne 3,6 passages pour obtenir du tissu tumoral. On a réussi à prélever des cellules tumorales et du tissu tumoral dans tous les cas. Une analyse cytologique, histopathologique et immunohistochimique a été réalisée (100 %; n = 5/5). Les diagnostics comprenaient le mélanome (60 %; n = 3/5), le mélanocytome (20 %; n = 1/5) et le léiomyome (20 %; n = 1/5). L'hyphéma postopératoire transitoire avait disparu après 1 semaine (80 %; n = 4/5). Aucun cas de glaucome secondaire, d'infection ou de cataracte n'a été observé.
La biopsie par aspiration-section à travers la racine de l'iris représente une méthode sûre et peu invasive pour obtenir des cellules du corps ciliaire en vue d'analyses cytologiques, histopathologiques et immunohistochimiques.
Ciliary body tumours remain a diagnostic challenge.
However, the clinical diagnosis of ciliary body tumours remains a challenge. Biopsy remains an indispensable tool for diagnosis of select ciliary body tumours and remains the only way to allow cytologic, histopathologic, immunohistochemical, genetic, and molecular analysis.
Herein, we present a new method of biopsy for ciliary body tumors.
Methods of obtaining tumour tissue can be divided into tumour excision or biopsy. Excision, incisional biopsy, or iridocyclectomy in the case of ciliary body tumors provides the most tissue and is preferable for pathology analysis. However, for iridocyclectomy the goal is to excise the entire tumour with margins.
Therefore, iridocyclectomy requires a large corneal and/or scleral dissection and hemostasis of the surrounding uvea and typically affects the adjacent tissues (vitreous, zonules, and lens). Excisional biopsy has been associated with secondary glaucoma, hemorrhage, retinal detachment, and cataract as wells as risks endophthalmitis. The resultant wounds are large, can induce astigmatism, and require closure with sutures. Iridocyclectomy typically results in a dysmorphic, poorly functioning pupil associated with symptoms of glare.
The FNAB procedure uses a 25-gauge needle through the sclera or cornea. Trans-scleral FNAB relies on presurgical localization by clock hour or evidence of tumour extension through the angle. Trans-scleral FNAB creates as sclerotomy through which tumour cells can exit the eye. In contrast, with trans-corneal FNAB, the needle passes into the anterior chamber and then into the tumour. If cells are liberated from the tumour, the keratotomy will merely allow them to exit the body. With both FNAB techniques, the surgeon uses the sharp needle tip to liberate cells while an assistant manually creates suction with a syringe attached to extension tubing.
Manually created suction is inherently poorly controlled. It often results in a situation where a sharp needle is located in an unstable anterior chamber risking puncture or lacerating of the iris, lens, lens capsule, corneal endothelium, and vasculature. Other risks of the procedure include persistent hyphema, which has been reported in 6%.
FNAB typically provides cells (not tissue) for cytological analysis. If possible, tissue pieces must be skilfully needle-tip-carved and then aspirated. FNAB of ciliary body tumors involves placing the needle through the peripheral iris or sclera to a position where its sharp tip cannot be observed while sampling the tumour or interacting with adjacent tissues. From a trans-scleral approach, the needle tip is directed at the natural lens.
In contrast, iris, sclero-invasive, and orbital tumors have been biopsied using machine-modulated, aspiration-cutter-enhanced methods under viscoelastic stabilization of the anterior chamber.
Unlike FNAB, the aspiration cutter probe does not have any exposed sharp edges that can injure intraocular structures. Furthermore, aspiration is modulated by the surgeon. This study investigates the use of Finger's aspiration-cutter technique for trans-iris biopsy of ciliary body tumors.
Materials and Methods
Five patients with ciliary body tumors that had demonstrated growth or atypical features or who required a pathology diagnosis before consenting to treatment were considered for biopsy (Table 1). Observation, biopsy, and treatment without a pathology diagnosis were discussed and offered to each patient. This study and informed consent adhered to the guidelines of the Health Insurance Portability and Accountability Act of 1996 (HIPAA), the Code of Ethics of the World Medical Association, and the tenets of the Declaration of Helsinki. Internal review board (IRB) and ethics approvals for retrospective chart review and analysis were obtained from The New York Eye Cancer Center IRB.
This research was generated from a clinical practice (The New York Eye Cancer Center) that uses operating rooms and pathology services at an institution (The New York Eye and Ear Infirmary of Mount Sinai).
To prevent post-viscoelastic glaucoma and stretch the iris with miosis, eyes were pretreated with pilocarpine 2% one hour before surgery. All surgeries were performed by one surgeon (P.T.F.). An operating microscope was used to maximally visualize the anterior segment. The patient was prepped, draped, and placed under anaesthesia. Then a 0.3 forceps was used for countertraction, whereas an inked 27-gauge trocar was used to create a blue, visible, shelved incision through clear juxtalimbal cornea (opposite from the tumour midline; Fig. 1). Sodium hyaluronate 1% (Johnson & Johnson, Santa Ana, CA) was placed to fill and thus deepen the anterior chamber as well as stabilize the iris.
Then, the 27-gauge aspiration cutter (Alcon, Fort Worth, TX) was inserted into the anterior chamber with its opening against the stroma at the iris root. Once a full-thickness iridotomy was created, the cutter was advanced into the ciliary body and tumour (Fig. 1). Initial aspiration-cutter settings were 300 mm Hg and 600 cuts per minute. These settings were adjusted (as necessary) to maximize efficiency while keeping suction and cutting rates to a functional minimum.
Tumour aspiration cutting typically lasted less than 30 seconds. After each pass, the aspiration-cutter probe was removed from the eye. An empty 3 mL syringe was attached to the effluent connector after which the aspiration-cutter portal was placed into a cup of sterile saline solution. The 3 mL syringe plunger was withdrawn as to cause 0.5–1.0 cc of saline to flush the biopsy specimen from the tubing into the syringe. Once disengaged from the tubing, the syringe and its contents were examined under the microscope for adequacy. With this standard, a median 3 biopsy passes were performed for each case. Samples were immediately processed by pathology for analysis (Table 2). Our methods of cytopathologic, histopathologic, and immunohistochemical specimen analysis have been discussed in prior publications.
Significant smooth muscle proliferation with inflammatory cells
Rare entrapped reactive astrocytes (GFAP+ and S-100+), rare spindle and normal uveal melanocytes (melan-A+), reactive irregular pigmented/nonpigmented epithelial cells (Cam 5.2+), no neuronal cells (synaptophysin−), desmin−, smooth muscle spindle cells (actin+) Enucleation showed smooth muscle actin+ leiomyoma of ciliary body and anterior choroid
IOP, intraocular pressure; POD, postoperative day; Melan-A, a protein found in melanocytes; HMB-45, human melanoma black; Ki-67, a marker for cell proliferation; A, first biopsy; B, second biopsy; HM, hand motions; GFAP, glial fibrillary acidic protein; S-100, low-molecular-weight protein; Cam 5.2, marker for myofibroblasts; Actin, protein that forms microfilaments.
The sodium hyaluronate 1% was irrigated or aspirated from the eye and replaced with balanced salt solution. The corneal incision was checked for leakage (Seidel) and no sutures were required. Subconjunctival antibiotic steroid was injected, and topical antibiotic steroid ointment was placed. Operative eyes were closed and covered with an eye shield. Postoperative topical and oral ocular hypotensive agents were employed until their postoperative day 1 pressure check.
Five consecutive patients underwent micro-incision, aspiration-cutter biopsy for their ciliary body tumors. In one case (#4), a conclusive diagnosis could not be made after the first biopsy; therefore, that patient received a second biopsy (Table 2). Cells and tissue were provided for pathology analysis and diagnoses were issued for each case (Fig. 2). No persistent hyphema, secondary glaucoma, or vision loss was noted.
Pre-operative images of 2 representative cases are presented to illustrate 2 of the anterior uveal tumors considered amenable to Finger's aspiration-cutter technique biopsy through the iris root. Case #2 reveals a normal-appearing anterior chamber angle anterior obscuring the subjacent ciliary body melanoma best seen on UBM (Fig. 3A, B). Case #3 shows minimal anterior chamber angle involvement anterior to what biopsy proved to be a large, dome-shaped ciliary body melanocytoma (Fig. 3C, D).
Overall, 3 patients were diagnosed with ciliary body melanoma. One was a melanocytoma and 1 was eventually found to be a leiomyoma after enucleation.
In 5 of 6 procedures, 3 passes were required to achieve specimen. Two surgeries for a total of 10 passes were required for 1 patient (case #4) with leiomyoma (Table 2). This case emphasizes the difficulty diagnosing pigmented ciliary body leiomyomas by anything but gross tissue staining for smooth muscle actin.
No sutures were required to close the corneal entry wounds.
Although no patient developed a postoperative intraocular pressure spike, 4 cases exhibited a small hyphema (1 mm or less) all of which resolved after 7–10 days. Visual acuities remained stable by their postoperative 1-month visit (Table 2). No patients experienced corneal edema, glare, retinal detachment, glaucoma, or dysphotopsias after the procedure. There were no instances of inadvertent damage to lens, capsule, or nearby iris tissues.
Long-term follow-up for complications related to biopsy was not possible in that each tumour was treated soon after biopsy-aided diagnosis (Table 3).
Table 3Tumour treatments
Postbiopsy clinical course
Ciliary body melanoma
Plaque brachytherapy 3 weeks after biopsy
Ciliary body melanocytoma
Plaque brachytherapy same day as biopsy
Ciliary body melanoma
Enucleation 1 month after biopsy
Lost to follow-up for 1 year, received enucleation 1 week after re-establishing care
Ciliary body melanoma
Systemic radiation and immunotherapy for metastasis 3 months after biopsy
Ciliary body tumour biopsy was performed through the iris root using a 27-gauge aspiration cutter. All specimens were adequate for cytologic and histopathological analysis. Cells for cytology (100%, n = 6/6), tissue for histopathology (100%, n = 6/6), and immunohistochemistry (50%, n = 3/6) were obtained. No crush artifact were noted to prevent evaluation. A pathologic diagnosis was accurate in 4/5 (80%) cases. As is common, the 1 tumour that was not diagnosed by this method was not a melanoma but rather found to be a leiomyoma after enucleation.
No patients experienced post-treatment elevations of intraocular pressure. Four cases (66.7%) experienced transient hyphemas, which cleared within 7–10 days.
Micro-incision, trans-iridal, aspiration-cutter-assisted biopsy of ciliary body tumors offers several key advantages. Given the size of the 27-gauge aspiration cutter, the biopsy can be performed through a small self-sealing clear corneal incision that did not require a suture for closure. The blunt-tipped aspiration cutter with machine-assisted, foot-pedal-modulated aspiration and cutting provides a more controlled biopsy approach compared with FNAB (which uses a sharp-needle-tip and assistant-controlled manual suction). Our approach appeared to minimize the risk of damage to normal intraocular structures. In this case series, the 27-gauge minimally invasive aspiration cutter approach was an effective method to obtain enough ciliary body tumour cells and tissue to perform, cytologic, histopathologic, and immunohistochemical diagnostic results without significant complications (Table 2).
The risk of seeding of tumour cells during biopsy within and around the eye is poorly understood. Clearly individual tumour cells cannot be seen, even with the aid of an operating microscope or surgical loupes. Schefler et al. showed that the tumour cells are liberated by fine-needle aspiration, vitrectomy, and open biopsy.
Not currently quantified, this risk is likely small. However, our clear corneal approach liberates such cells to the outside world, thus eliminating the risk of spread beneath the conjunctiva and into the orbit. All anterior segment biopsy methods will liberate tumour cells into the anterior chamber. However, over the last 15 years since Finger's aspiration-cutter technique first used for biopsy of iris tumors as well as additional years of experience with anterior chamber FNAB, we have seen no cases of tumour re-implantation nor on PubMed review have others reported such in the iris or cornea.
The weaknesses of this study include its small number of patients, retrospective design, and length of follow-up. Specifically, initiation of tumour treatment soon after biopsy precluded the long-term monitoring of biopsy-related adverse events. However, the strengths of this study include the first author's invention of this method for iris tumour biopsy, the comparatively lower secondary hyphema rates (compared with FNAB and excision of iris tumors), as well as that we were able to retrieve both cells and small fragments of tissue. Our trans-corneal approach provided some safety against systemic tumour dissemination.
Herein, we present a new biopsy technique for ciliary body tumors. This pilot study provides evidence that micro-incision, trans-iridal, ciliary body tumour biopsy can safely be performed using a 27-gauge aspiration cutter while the anterior chamber depth is maintained with viscoelastic. No complications that might preclude clinical use of this technique were noted, and thus further study is warranted.
Footnotes and Disclosure
The authors would like to acknowledge The Eye Cancer Foundation, Inc (http://eyecancercure.com), for its financial support for the costs of presenting and publishing this research. However, The Eye Cancer Foundation played no role in the study design, collection of data, or its analysis or interpretation. The foundation played no role in writing the report or decision to submit this study for publication. The authors hereby acknowledge Robert Masini (New York Eye and Ear Infirmary of Mount Sinai, New York City, NY) for his assistance in creating the illustrative figure for the article.
Paul T. Finger, MD, Michael Chua, MD, and Codrin Iacob, MD, have no financial relationships or conflicts to disclose. Dr. Michael Chua received a National Eye Institute Travel Grant to the ARVO 2020 Annual Meeting, San Francisco, CA.