transpupillary thermotherapy for choroidal melanoma

Transpupillary Thermotherapy for Choroidal Melanoma

Tumor Control and Visual Results in 200 Consecutive Cases

Carol L. Shields, MD, Jerry A. Shields, MD, Jacqueline Cater, PhD, Noemi Lois, MD, Chaim Edelstein, MD, Kaan Gtindtis, MD, Gary Mercado, MD

Objective: The authors evaluated the results of primary transpupillary thermotherapy for choroidal melanoma in 100 cases.

Design: Prospective nonrandomized analysis of treatment method. Participants: One hundred patients with choroidal melanoma were studied. Main Outcome Measures: Tumor response, ocular side effects, and visual results. Results: Of 100 consecutive patients with choroidal melanoma treated with transpupillary thermotherapy, the

mean tumor basal diameter was 7.1 mm and tumor thickness was 2.8 mm. The tumor margin touched the optic disc in 34 eyes (34%) and was beneath the fovea in 42 eyes (42%). Documented growth was present in 64 eyes (64%) and known clinical risks for growth were present in all of the remaining 36 eyes (36%), with an average of 4 of 5 statistical risk factors for growth per tumor. After a mean of three treatment sessions and 14 months of follow- up, the mean tumor thickness was reduced to 1.4 mm. Treatment was successful in 94 eyes (94%) and failed in 6 eyes (6%). Three patients with amelanotic tumors showed no initial response to thermotherapy, but subsequent intravenous indocyanine green administration during thermotherapy resulted in improved heat absorption and tumor regression to a flat scar. The six eyes classified as treatment failures included four eyes with tumors that showed partial or no response to thermotherapy, thus requiring plaque radiotherapy or enucleation, and two eyes with recurrence, subsequently controlled with additional thermotherapy.

After treatment, the visual acuity was the same (within 1 line) or better than the pretreatment visual acuity in 58 eyes (58%) and worse in 42 eyes (42%). The main reasons for poorer vision included treatment through the foveola for subfoveal tumor (25 eyes), retinal traction (10 eyes), retinal vascular obstruction (5 eyes), optic disc edema (1 eye), and unrelated ocular ischemia (1 eye). Temporal location (versus nasal and superior, P = 0.02) and greater distance from the optic disc (P = 0.04) were risks for retinal traction.

Conclusions: Transpupillary thermotherapy may be an effective treatment for small posterior choroidal melanoma, especially those near the optic disc and fovea. Despite satisfactory local tumor control, ocular side effects can result in decreased vision. Longer follow-up will be necessary to assess the impact of thermotherapy on ultimate local tumor control and metastatic disease. Ophthalmology 7998; 705587 -590

There are several methods available for the management of choroidal melanoma, including enucleation, plaque radiotherapy, charged-particle radiotherapy, local resection, laser photocoagulation, and observation.‘72 Unfortunately,

Originally received: May 9, 1997. Revision accepted: September 15, 1997.

From the Ocular Oncology Service, Wills Eye Hospital, Thomas Jeffer- son University, Philadelphia, Pennsylvania.

Support provided by the Paul Kayser International Award of Merit in Retina Research, Houston, Texas (J. Shields); the Macula Foundation, New York, New York (C. Shields); and the Eye Tumor Research Foun- dation, Philadelphia, Pennsylvania.

The authors do not have proprietary interest in any of the devices in this article.

Reprint requests to Carol L. Shields, MD, Ocular Oncology Service, Wills Eye Hospital, 900 Walnut Street, Philadelphia, PA 19107.

the management of small melanoma located near the optic disc and fovea is difficult and associated with substantial visual impairment. More recently, transpupillary thermotherapy has been popularized as an important treatment for relatively small posterior choroidal melanoma.“Z4

Transpupillary thermotherapy is a technique that employs near infrared light delivered as heat to treat selected ocular conditions. This technique has been used to treat retinoblastoma’ and choroidal melanoma.334 Transpupil- lary thermotherapy offers an over 90% tumor control rate for properly selected retinoblastoma in our experience. With regard to melanoma, the heat has been documented to penetrate 4 mm depth within a tumor, inducing necrosis along the absorption pathway of the beam within the tumor.“-” We have employed transpupillary thermotherapy as a supplement to plaque radiotherapy and as a primary

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treatment for selected choroidal melanoma. Two reports have been published on small groups of patients with choroidal melanoma treated with transpupillary thermotherapy alone.3x4 Oosterhuis and coworkers3 reported on 3 patients and Shields and associates4 on 17 patients treated with transpupillary thermotherapy alone. Both groups found the treatment to be effective for small posterior choroidal melanoma. In this report, we evaluated the early experience with our first 100 consecutive patients with choroidal melanoma treated with transpupillary thermotherapy alone. We assessed tumor control and ocular side effects, as well as visual results using this technique.

Patients and Methods

A prospective evaluation was performed on all patients with choroidal melanoma treated with transpupillary thermotherapy alone at the Ocular Oncology Service at Wills Eye Hospital between January 1995 and September 1996. Those patients treated with transpupillary thermotherapy as an adjunct to plaque radiotherapy were excluded. The patients were not ran- domized to thermotherapy, but were treated selectively on the basis of clinical factors and patient preference. The eligibility criteria for treatment included patients with primary choroidal melanoma measuring 12.0 mm or less in base and 4.0 mm or less in thickness, located posterior to the equator of the eye, and with evidence of documented growth or substantial tumor risk factors for growth or metastasis.” In special circumstances, tumors greater than 4.0 mm, but with a small base less than 8.0 mm abutting the optic nerve, were eligible. Excluded were those patients with tumor invasion of the retina, optic disc, vitreous, or sclera or those patients with subretinal hemorrhage or media opacity prohibiting adequate visualization of the tumor. Subreti- nal fluid measuring more than 3.0 mm in elevation overlying the choroidal tumor was an exclusionary factor. The initial 17 patients in this study were reported previously,4 but are included here with a more detailed analysis and longer follow-up.

The patient data included age, race, gender, and visual acuity at initial examination. The tumor data included largest tumor base (in millimeters, measured by indirect ophthalmoscopy), greatest tumor thickness (in millimeters, measured by A-scan and B-scan ultrasonography), proximity of the tumor margin to the optic disc and foveola (in millimeters, measured by indirect ophthalmoscopy), meridional location of the center of the mass (nasal, superior, temporal, inferior, macula [- 3 mm to foveola]), pigmentation (yellow, light brown, dark brown), subretinal fluid (present, absent), orange pigment on the tumor surface (present, absent), and photographic evidence for documented growth.

The treatment was delivered using a specially modified infrared diode laser at 810 nm, with an adjustable beam width of 1.2 mm, 2.0 mm, and 3.0 mm. The infrared delivery system was adapted to a slit-lamp biomicroscope and delivered through a contact lens. The treatment protocol has been described.4 Fur- ther treatments were performed to reach the endpoint of a regressed tumor into an ophthalmoscopically flat chorioretinal scar.

At each follow-up period, the visual acuity and ultrasonographic tumor thickness were measured. Fundus photography, fluorescein angiography, and indocyanine green angiography were selectively performed. Associated anterior segment and fundus findings were recorded. Specifically, the presence of

582

cornea, iris, lens, retina, and optic disc changes was recorded. Statistical analysis of the impact of the clinical variables on the development of retinal traction was performed using logistic regression.

Results

Between January 1995 and September 1996, we treated 100 patients with choroidal melanoma using transpupillary thermotherapy as the only treatment. During this same period, 91 patients with medium and large melanoma were treated with combined plaque radiotherapy and thermotherapy, but these data were not included in this analysis. At the time of data collection on the 100 cases treated with transpupillary thermotherapy alone, there was a mean of 14 months follow-up (range, 6 to 24 months). The mean patient age at treatment was 54 years (range, 20 to 85 years). All patients were white. There were 47 women and 53 men.

The visual acuity prior to treatment was 20/20 in 44 eyes (44%), 20/25 in 15 (15%), 20/30 in 10 (lo%), 20/40 in IO (lo%), 20/50 in 5 (5%), 20/60 in 5 (5%) 20/70 in 2 (2%), 201 80 in 2 (2%), 20/100 in 1 (I%), 20/200 in 4 (4%), and 20/400 in 2 (2%). The tumor meridian was nasal in 14 (14%), superior in 24 (24%), temporal in 11 (1 1%), inferior in 12 (12%) and macula in 39 (39%). The posterior tumor margin was a mean of 2.2 mm from the optic disc margin (range, 0 to 7.0 mm; median, 2.0 mm) and a mean of 2.2 mm from the foveola (range, 0 to 9.0 mm: median, 2.0 mm) (Fig 1). Thirty-four tumors (34%) touched the optic disc margin, and 42 tumors (42%) involved the fovea1 area (Fig 2). The tumor overhung the optic disc in seven patients (7%), and when present the mean overhang was 38% of the optic disc surface. The mean tumor base was 7.1 mm (range, 3.0 to 12.0 mm; median, 6.5 mm) and mean tumor thickness was 2.8 mm (range, 1.6 to 5.1 mm; median, 2.8 mm).

A secondary retinal detachment was present in 90 eyes (90%), and it involved the fovea in 50 eyes (50%). Orange pigment clumps on the tumor surface were observed in 75 eyes (75%). (Figs 1 and 2) Growth had been photographically documented in 64 cases (64%) prior to treatment (Fig 3). Of all 100 tumors, published risk factors for growth and metastases of small pigmented choroidal tumors were present in every case, and the average number of risk factors for growth was four per tumor and risk factors for metastases was three per tumor.”

The mean number of treatment sessions per tumor was three (range, one to six sessions) (Fig 4). The sessions were delivered at a mean interval of 3 months. The mean treatment parameters at the first session included power at 729 mW (range, 300 to 1200 mW) for 11 minutes (range, 5 to 24 minutes) using typically a 3-mm spot size (1.2- and 2.0-mm spot size also employed). The immediate treatment endpoint was a blanched white appearance in 38 tumors (38%), grey-white in 48 (48%), and no change in tumor appearance in 14 tumors (14%).

The mean tumor thickness measured ultrasonographicallj prior to treatment was 2.8 mm. The mean tumor thickness grad- ually decreased to 2.0 mm at month 3, 1.7 mm at month 6, 1.6 mm at month 9, 1.5 mm at month 12 after initial treatment, and stabilized thereafter (Fig 5). At the last examination at a mean of 14 months after treatment, the ultrasonographic mean tumor thickness including choroid and overlying retinal tissue was 1.4 mm; however, tumors that measured less than 1.5 mm thick with ultrasound often appeared to be flat ophthalmoscopically, and the measurement was judged to reflect the atrophic choroid

gure 1. A 40-year-old woman

th 20/20 wsual acuty was

und to have a documented

owrng choroldal melanoma

th subret& fluld and orange

gment. A, fundua photograph

fore thermotherapy (Decem-

r 1995). The tumor measured

9 mm In thickness Note the

ange pigment on the rnfermr

xtmn of the nxass and the su-

etmal flud over the mfermr

Id temporal margm. 8, fundus

lotograph munedlately after

ermotherapy (December

j95). The tumor demon-

rated a gray-white appear-

Ice. C, fundus photograph

fter three sesxons of thermo-

lerapy (April 1997). The tu-

mr regressed to a flat scar wth

entral flat pigment and a sure

xmd of wslble sclera. Mild ret-

lal tractmn along the mfermr

ortwn of the scar was noted.

), fundus photograph after

xee bessmnb of thermotherapy

April 1997). The optic nerve

nd fovea were healthy. The

atlent’s vlaudl dculty remams

O/25 at 16 months follow-up.

4dd retmal trxtwn 1s noted at

he mferlor margm of the treat-

lent site Attenuanon of the

ranch retmal artery and vem

t the site LS ewdent.

‘igure 2. A 49-year-old man

/lth 20/20 visual acuq was

xmd to have a documented

rowmg choroldal melanoma

Jxh subretIna fluid and orange

lgment. A, fundus photograph

2 xfore thermotherapy (Febru-

Iry 1996) The tumor measured

2.3 mm m thickness. Note the

llffuse orange pigment over the

nass and the subreunal flud m-

volwng the fovea and temporal

nargm. B, fundus photograph

lmmedlately after thermother-

apy (February 1996). The tu-

mor showed a confluent gray-

white appearance. C, fundus

photograph 3 months after one

,esbmn of thermotherapy (May

1996) The tumor shows early

regressIon and the subretmal

flud has resolved. D, fundua

photograph after two besswnb of thermotherapy (October I ne tumor regresses to a tlat scar wtn central pigment and a wrround of vwble

&~a. HI\ wtual acuity decreased to hand motmns after treatment, and the findmgs were stable over 12 montha of follow-up. Attenuatmn of the branch

retlnJl artery and vem <It the site 15 ewdent

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Volume 105, Number 4, April 1998

Figure 3. A 45,year-014 111 with ZO/ZO visual acuity was found to have an amelanotic choroidal melanoma. A, fun otograph at initial visit (January 1995). An amelanotic tumor was found nasal to the optic disc. The mass was observed. 8, fundus photograph 7 monrhs later (August 1995). The

tumor demonstrated growrh. The tumor thickness was 7.5 mm and thermotherapy was performed. C, fundus photograph after three sessions of thermotherapy

(January 1996). There was minimal regression of the tumor, and retinal pigment hyperplasia at the tumor margin was noted. D, fundus phorograph after

an additional session of thermotherapy and indocyanine green enhancement (January 1997). Th 3 t L umor regressed to flat residual scar with visible underlying sclera. The patient’s visual acuity is 20/20 at 18 months follow:up. Arrenuarion of the branch retinal artery and vein at the site is evident.

1 2 3 4 5 6

Number of treatment sessions

Shields et al - Transpupillary Thermotherapy

Figure 5. Tumor thickness at the time of treatment (0 months) and upon follow-up at 3, 6, 9, and 12 months m 100 consecunve pattents wth chorordal melanoma treated wth transpuplllary thermotherapy.

--~ ---_lllllll---.

3 6 9 12 Time after treatment (months)

and overlying retinal scar tissue. The ophthalmoscopic assess- after transpupillary thermotherapy alone-was 3.2 mm, and after ment of tumor thickness after treatment was flat chorioretinal indocyanine green-enhanced transpupillary thermotherapy was scar in 63 cases (63%) and less than 1.5 mm in 80 cases (80%). 1.0 mm.

The treatment was successful in 94 eyes (94%) and failed in 6 eyes (6%) (Table 1). Those with successful treatment demonstrated regression of the tumor to a flattened central scar with visibility of the sclera through the surround of choroidal atrophy. Of the 94 successful eyes that showed ultimate tumor regression, 87 eyes showed immediate complete regression, 4 eyes showed initial partial regression, and 3 eyes showed initial minimal or no regression. The four eyes with partial regression demonstrated regression of the majority of the tumor but persis- tent thickness of a tumor margin and necessitated additional thermotherapy with wide margins of treatment for complete tumor control. The three eyes with minimal or no initial regression all contained amelanotic choroidal melanoma, and subsequent addition of intravenous indocyanine green as an adjuvant to increase heat uptake allowed for regression of all three tumors (Fig 6). The indocyanine green was injected over 20 seconds by an intravenous route (100 mg indocyanine green in 10 cc aqueous solvent). The injection was commenced 1 minute after the start of thermotherapy. The mean ultrasonographic thickness of these three amelanotic tumors prior to treatment was 3.5 mm,

The six eyes classified as treatment failures included four eyes with little or no response and two eyes with tumor recurrence. In the four eyes with little or no response, three tumors were amelanotic, treated with high-energy settings, and showed no response while one tumor was pigmented but demonstrated continued growth after treatment requiring plaque radiotherapy. The three amelanotic tumors were treated before we employed indocyanine green enhancement, and therefore this technique was not used. The three amelanotic tumors were subsequently treated with plaque radiotherapy in one case and enucleation in two cases.

Only two cases in this series demonstrated tumor recurrence. In both cases the tumor was pigmented and demonstrated an excellent initial response to treatment. The recurrence occurred at a mean of 10 months after three sessions of treatment and appeared at a margin in both cases. The recurrence measured a mean of 4 mm base and 1.4 mm thickness. In one case, it occurred along the posterior margin near the fovea in a region where the treatment was lighter and margins tighter to preserve vision. In the other case, the recurrence was at the far peripheral margin. In both cases, tumor regression was achieved with two additional sessions of transpupillary thermotherapy.

Table 1. Tumor Control in 100 Consecutive Patients with Chorotdal Melanoma Treated with Transpupillary

Thermotherapy*

Tumor Control % of Patients

Treatment success (tumor regresslon complete) Treatment fadure

Tumor regresslon partial Tumor regresston absent Tumor recurrence

94 6 1 3 2

* All of the cases of incomplete regression occurred in the first 50 patients. Of the last 50 patients there has been tumor regression complete in all cases.

When comparing our first 50 cases with our last 50 cases of transpupillary thermotherapy for choroidal melanoma, we found that all of the treatment failures occurred in the first 50 cases over a mean follow-up of 19 months. In the last 50 cases, there has been successful tumor control with transpupillary thermotherapy in all cases and thus far no failures; however, the mean follow-up is only 9 months. This may reflect a difference in the follow-up or the learning curve of the technique.

The final visual acuity was 20/20 in 30 eyes (30%), 20125 in 11 (ll%), 20/30 in 11 (1 l%), 20/40 in 5 (5%), 20/50 in 5 (5%), 20/60 in 6 (6%), 20/70 in 1 (l%), 2OBO in 1 (l%), 20/ 100 in 4 (4%), 20/200 in 4 (4%), 20/400 in 6 (6%), count fingers in 14 (14%), and hand motions in 2 (2%) (Fig 7). In 58 eyes (58%) the visual acuity was within 1 line or improved compared with the initial vision, and in 42 (42%) the visual acuity de-


Figure 6. The combination of transpupillary thermotherapy (TTT) and indocyanine green (ICG) enhancement was employed in three patients with nonpigmented choroidal melanoma who initially showed no response to one or more sessions of trans- pupillxy thermotherapy alone.

creased. The reason for improved vision was resolution of subretinal fluid. The main reasons for poorer vision included treatment through the foveola for subfoveal tumor (25 eyes), retinal traction (10 eyes), retinal vascular obstrnction (5 eyes), optic disc edema (1 eye), and unrelated ocular ischemia (1 eye). All patients were alive, with no evidence of melanoma metastasis.

Complications of transpupillary thermotherapy were found in 39 patients (39%) and were usually limited to the site of treatment. In 61 eyes (61%), there were no complications of treatment. Of all 100 patients, there were no occurrences of direct heat-related alterations in the cornea, lens, or vitreous. No patients developed glaucoma, tumor extension through Bruch’s membrane, choroidal hemorrhage, retinal hole formation, rhegmatogenous retinal detachment, or scleral necrosis. Retinal edema and fine intraretinal hemorrhages at the site of heat treatment were commonly observed immediately after treatment. The complications of treatment (Table 2) included focal iris atrophy and posterior synechia in 1 eye (mean time interval of 3 months), overlying branch retinal artery occlusion in 12 eyes (mean time interval of 4 months), overlying branch retinal vein

Figure 7. Visual acuity before and after transpupdlary thermotherapy for choroldal melanoma in 100 consecutive cases.

T-IT ‘I-IT+ICG enhancement

Type of treatment (at 3 month intervals)

occlusion in 23 eyes (mean time interval of 5 months), retinal traction in 20 eyes (mean time interval of 5 months), macular edema in 4 eyes (mean time interval of 5 months), focal neovascularization of the retina in 6 eyes (mean time interval of 5 months), and optic disc edema in 1 eye (mean time interval of 4 months). All patients with branch retinal artery obstruction had concomitant branch retinal vein obstruction. Neovasculari- zation of the retina occurred presumably secondary to branch retinal vein obstruction. Management of these problems was observation in all cases except for the patients with retinal neovascularization, who were treated with panretinal photocoagulation, with subsequent regression of the neovascularization in all but one case.

Evaluation of the tumor and treatment in those 20 eyes that developed retinal traction showed tumor location to be nasal in 0 cases (O%), inferior in 3 (3%), temporal in 5 (25%), superior 2 (lo%), and macular in 10 cases (50%). The mean tumor base was 7 mm, tumor thickness was 3 mm, proximity to optic disc was 3 mm, and proximity to foveola was 2 mm. The mean number of sessions was three, and treatment power was 702

Before treatment I

After treatment

Visual acuity

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Shields et al * Transpupillary Thermotherapy

Table 2. Ocular Side Effects of Transpupillary Thermotherapy for Choroidal Melanoma in 100 Consecutive Patients

Ocular Tissue

Cornea Edema Scar

Iris Irlcis Iris atrophy Postermr synechia

Lens Edema Cataract

Retina

NO.

0 0

0 1 1

0 0

Time Interval

(mos, mean)

- -

3 3

vent DNA repair. Treatment parameters for choroidal melanoma are more aggressively designed to be directly cytotoxic to induce cell necrosis. With retinoblastoma, the infrared radiation is delivered alone or in combination with chemotherapy for approximately 10 to 40 minutes to the center of the malignant retinal tumors5 Often two or three sessions of treatment are necessary for full-thickness tumor destruction. In our experience, thermotherapy offers excellent tumor control for properly selected retinoblastoma and is emerging as a very important treatment method for small to medium retinoblastoma.

Branch retmal artery occlusmn (BRAO)”

Branch retmal vem occlusion (BRVO)*

Retinal tractmn Retmal exudation Macular edema Neovascularizatton retma

(NVE)t Neovascularization disc Retinal hole Rhegmatogenous retinal

detachment Optic disc

Optic disc edema Optic atrophy

12 4

23 5 20 5 0 4 7

6 5 0 - 0

0 -

1 4 0 -

With choroidal melanoma, the thermotherapy technique and expected results are different from retinoblastoma. The heat is delivered over the entire surface of the tumor using large overlapping treatment spots of l-minute duration each, accumulating a total treatment time of 20 to 40 minutes. Choroidal melanoma typically shows a visible whitening of the tumor and the overlying retina immediately after treatment. Transpupillary thermotherapy causes relatively rapid regression of melanoma compared with plaque radiotherapy’S for a comparable size tumor, and the heat-treated tumor regresses over a 3- to 6-month period to a flat scar. 3*4 In our series, once satisfactory regression was achieved, the tumor remained regressed in 94 of 96 cases (98%). However, it is important to realize that more follow-up will be necessary to deter- mine if long-term recurrences will develop.

* No patients had BRA0 alone, 11 had BRVO alone, and 12 had combi- natton BRA0 plus BRVO.

t NVE secondary to branch retinal vein occlusion in all six cases.

mW. A comparison of the eyes that developed retinal traction with those that did not develop retinal traction was made (Table 3). We did not evaluate vitreous detachment as a factor in surface wrinkling retinopathy; this will be assessed in the future. In the univariate analysis, the only factors found to be statistically related to the development of retinal traction included temporal quadrant (as compared with nasal and superior quadrants) and increasing distance from the optic disc. For every increase of 1 mm distance from the optic disc, the odds ratio increased by 1.3. In the multivariate analysis, temporal quadrant location maintained statistical significance (P = 0.03).

Discussion

Not all choroidal melanomas show an adequate response to thermotherapy. We found that 94% achieved successful regression without recurrence, and 6% failed treatment. Of the 94 successfully treated tumors, 4 showed initially only partial regression and 3 showed minimal or no regression. Those patients that showed initial partial or no regression had tumors that were amelanotic (therefore absorbing less of the delivered heat) or tumors that were very close to the foveola, and initial treatment was relatively lighter at the foveolar margin to spare vision. Tumor control was subsequently achieved in these cases by providing a wider margin of treatment in those with partial regression and providing indocyanine green enhancement for improved heat absorption in those with no regression. We have subsequently realized that treatment to the exact edge of a choroidal melanoma is often inadequate, allowing for continued tumor activity in some cases. We now believe that it is essential to deliver the thermotherapy to at least 1.0 to 1.5 mm of normal surrounding choroid. We attempt to spare the foveola and optic nerve if they are not touched by the tumor and if reasonable.

Transpupillary thermotherapy is a method of delivering Infrared radiation absorbs better in darkly pigmented heat through the dilated pupil into the posterior segment melanoma. We now use indocyanine green enhancement of the eye. 3-‘o This method, using infrared radiation as for amelanotic choroidal melanoma,” based on a prior the heat source, is used to treat certain intraocular tumors, report that showed increased heat uptake in amelanotic including retinoblastoma and choroidal melanoma. The melanoma in rabbits using indocyanine green chromo- technique of delivery for the two tumors is different. Reti- phore.13 In our study, indocyanine green enhancement noblastoma is less pigmented than choroidal melanoma, was used to treat only three amelanotic tumors that and the treatment technique often employs chemotherapy showed a suboptimal (minimal or no) response to thermo- so that treatment parameters are designed to disturb tumor therapy alone, and a favorable response with tumor re- cell integrity, allow chemotherapy penetration, and pre- gression was achieved. Our technique includes initiation

587


Table 3. A Comparison of Eyes with the Complication of Retinal Traction versus Those without Retinal Traction in 100 Consecutive Cases of Transpupillary Thermotherapy for Choroidal Melanoma

Clinical Feature

Age (yrs)* Tumor quadrant

Nd Inferior Temporalt Superior

Macula Tumor quadrants combined

Nasal, Inferior, superior Temporal, macula

Tumor base (mm)* Tumor thickness (mm)* Proxlmlty opnc disc (mm)*

Proximity foveola (mm)* Subretmal flutd

Absent Present

No. of treatment spots* Maximum treatment (mW)* power Treatment endpomt

No color change Grayt White

No. of sessions of thermotherapy Interval between sessions (mos)

Retinal Traction Retinal Traction Absent Present

54 52

14 0 9 3 6 5

22 2

29 10

45 5 35 15

7.2 7.0 2.7 3.0 2.0 2.0

2.3 1.9

8 2 72 18 10.9 11.2

736 702

13 1 37 11 30 8

2.7 2.8 3.1 3.2

P

0.43

0.02 0.56

0.04 0.37 0.02

0.07 0.16 0.04 0.41 1 .oo

0.75 0.51

0.22

0.84 0.45 0.28

Odds Confidence Ratio Interval

0.99 0.96, 1.02

0.1 NA, 0.7 0.4 0.1, 3.1

0.1 0.01, 0.9 0.4 0.09, 2.2 3.9 1.3, 11.6

1.0 0.75, 1.2 1.6 0.8, 3.2 1.3 1.01, 1.6 0.9 0.7, 1.2 1.0 02,51

1.1 0.9, 1.2 0.9 0.9, 1.01

0.3 0 03, 2.2

0.9 0.3, 2 5 1.2 0.8, 1.9 1.8 0.6, 4.9

NA = not applicable.

* Mean.

t Reference variable.

of thermotherapy for 1 minute to disturb the tumor cellu- lar integrity and then injection of indocyanine green dye. We speculate that the initial heat allows for increased leakage and staining of the tumor with dye, thus providing improved uptake of the heat.

We reserve thermotherapy for relatively small choroi- da1 melanoma. We do not advocate treating all small pigmented choroidal tumors. In fact, in this study, documented growth of the melanoma had been established in nearly two thirds of cases, and the remainder displayed many suspicious risk factors for potential tumor growth and metastasis. “Jo When evaluating patients with small pigmented choroidal tumors, 3 mm or less in thickness and suspected to represent malignant melanoma, it should be realized that metastatic disease occurs in only 3% to 6%.“.‘4 Statistically identified risk factors for metastatic disease for these small tumors include tumor thickness 2.0 to 3.0 mm, documented growth, location 0 to 3.0 mm from the optic disc, and presence of symptoms.” If all four risk factors are present, the chance for metastatic disease escalates to 25%.” In the group of patient in this study, the mean thickness was 2.8 mm, growth had been documented in 64%, the tumor was a mean of 2.2 mm from the optic disc and touched the optic disc in 34% cases, and symptomatic subfoveal fluid was present in

50%. The tumors that we treated that were less than 2 mm in thickness all had documented growth based on fundus photography. It is our clinical experience that once growth begins, it continues and does not cease. Therefore, it is evident that this group of patients had substantial risks for metastatic disease. There was a mean of three risk factors for metastasis per patient, accounting for a 15% risk for metastasis per individual.” Because of the deleterious effect that this transpupillary thermotherapy can have on visual acuity, it should be reserved for choroi- da1 melanoma with metastatic risks.

We are selective with regard to tumor size, location, color, and presence of overlying subretinal fluid in those tumors that we find suitable for transpupillary thermotherapy. Presently, when using thermotherapy as a sole treatment, we prefer to limit our use of this technique to choroidal melanoma less than 4 mm in thickness. Prior studies have found that thermotherapy can induce dra- matic uveal melanoma necrosis for up to 4 mm depth at the site of treatmenL6-” We suspect that most of the necrosis is achieved at the first or second treatment, but we generally deliver three sessions for assurance of more complete control. The end result is an atrophic flat or excavated chorioretinal scar, sometimes with residual flat pigment that we suspect is necrotic tissue as it resolves

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Shields et al * Transpupillary Thermotherapy

slowly over time. In those tumors greater than 4 mm in thickness, we generally combine plaque radiotherapy with thermotherapy. Location within 8 mm of the optic disc or foveola is preferred, and tumors anterior to the equator are more difficult to reach with thermotherapy and are preferably treated with plaque radiotherapy or local resection.‘.* Darkly pigmented tumors respond more favorably than nonpigmented tumors. Shallow subretinal fluid measuring 3 mm or less over the apex of the lesion poses little or no problem to treatment, but greater depth of subretinal fluid may cause heat dispersion and less effective treatment to the tumor. In addition, we have concern that heat-induced retinal atrophy with retinal hole formation could occur if there is appreciable overlying subretinal fluid.

In contrast to plaque radiotherapy and charged-particle irradiation, the complications of transpupillary thermotherapy generally remain limited to the area of treatment. The early findings showed no sign of heat-induced damage to the cornea or lens, but this may take months to years to become clinically apparent. Fundus complications were more apparent. Retinal vascular obstruction and retinal traction are the main complications and occur in 23% and 20%, respectively, in our series. The vascular obstruction occurs as a direct result of heat-induced vascular sclerosis. During treatment, the retinal vessels often appear undisturbed by the heat, even if it is delivered directly through a vessel. The vascular sclerosis generally occurs several months later. Neovascularization of the retina can occur, especially if a major retinal vein is oc- cluded, and we have found that panretinal photocoagulation is necessary.

Another bothersome complication is retinal traction, which occurred in 20 eyes in our series. Often the traction is visible on the surface and deep within the retina. When comparing the tumors in the eyes with retinal traction versus those without retinal traction, it was apparent that tumors in the temporal quadrant and macular region had a higher rate of this complication than those located na- sally. In fact, this was not seen in any nasal tumor after treatment. The tumor base, thickness, proximity to foveola, and treatment parameters were approximately the same between the two groups. However, a difference in proximity to the optic disc was found. Retinal traction was more often found when the tumor was more distant from the optic disc. In addition, another factor, the status of the posterior hyaloid (attached or detached) prior and during treatment, will need to be carefully evaluated in the future for its relationship to retinal traction.

There are advantages and disadvantages of transpupillary thermotherapy as compared to radiotherapy. The advantages include the more rapid visible reduction of tumor over a period of a few months, more focal treatment with less destruction of surrounding normal tissues, and the fact that this is an outpatient procedure not requiring hos- pitalization, thus reducing overall patient costs. Even though the central visual acuity after treatment was pre- served in over half the patients, we realize that this is only short follow-up, and long-term visual acuity could

be worse, especially when considering that most of these tumors were in visually vital areas. In fact, it should be kept in mind that heat-induced damage to the ocular struc- tures may not be clinically evident for months or years, similar to radiotherapy. The disadvantages of transpupillary thermotherapy for choroidal melanoma include the multiple treatment sessions, immediate destruction of overlying retina, and inability to treat larger tumors or those situated in the peripheral fundus. Similar to all studies on uveal melanoma, longer follow-up over 10 to 15 years will be required before definitive information is available on the ultimate visual acuity, local tumor recurrence, and systemic prognosis.‘4 We realize that this is a nonrandomized study and reports a relatively small group of patients with a rare tumor. In the short term, however, transpupillary thermotherapy appears to be a useful tool in the management of small choroidal melanoma, especially those in the juxtapapillary and fovea1 region.

Addendum

Since the termination of data collection for this study, additional follow-up data continue to be recorded (mean follow-up, 24 months). The above reported findings have remained generally stable except in three patients. One patient underwent enucleation for tumor recurrence in the juxtapapillary region that was mentioned in our results and initially controlled by additional thermotherapy; one patient required retinal detachment surgery for traction retinal detachment; and one patient underwent enucleation for progressive retinal neovascularization that was not controlled by panretinal photocoagulation (mentioned in the results). In this patient, the tumor, which was originally 3.2 mm in thickness, appeared clinically to be eradi- cated and flat, and histopathologic study of that eye failed to reveal convincing evidence of viable tumor.

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