FP253 : The Outcomes of Transpupillary Thermotherapy (TTT) in Circumscribed Choroidal Hemangioma (CCH)

Dr. Shruti Sridharan, S20111, Dr. Vikas Khetan, Dr. Bikramjit P Pal, Dr. Harshit Vaidya

Abstract 

Aim – To study the outcomes of transpupillary thermotherapy (TTT) in patients with circumscribed choroidal hemangioma (CCH).

Methods: 27 consecutive patients presenting to our tertiary eye care centre between 2011 to 2015 were included in this retrospective interventional case series. Patients with CCH were treated with TTT using infrared diode laser (810nm) with a median spot size of 1.2 mm, power of 250 mW and exposure time of 3 min.

Results: The mean age was 41 ± 14 years with a M:F ratio of 3.5:1. The tumour dimensions (median[mm]; range[mm]) were: thickness (3.4; 1.5-5.8); horizontal diameter (7.6, 2.7-12); vertical diameter (7.3, 3.1-13.6). The size and location of the lesion did not significantly affect the final visual outcome. An average of 2.7 sessions was needed in the study group. Vision either improved or maintained in 66% of the patients (18/27) whereas it worsened in 33% (9/27).

Conclusion: TTT is an effective treatment modality in patients with CCH

INTRODUCTION:

Choroidal hemangiomas are benign vascular hamartomas of the choroid that present as two subtypes: Circumscribed and diffuse.The circumscribed choroidal hemangioma (CCH) is usually a sporadic tumor not associated with any systemic manifestations, although it can rarely be associated with Sturge-Weber syndrome or its variations, probably representing a limited form of the syndrome. ^[1],[2]

Circumscribed choroidal hemangioma is commonly asymptomatic and usually diagnosed in adulthood during routine eye examinations or when it causes symptoms including decreased vision, visual field defects, or metamorphopsia.^[1]Average patient age for development of symptoms appears to be in the late twenties to fifties, with a range of 6 to 75 years, depending on the series reported.^[1],[3] More than 90% of reported cases have been in Caucasian patients but there is no sex predilection.Hemangiomas of the choroid are classified histopathologically according to the type of vessels within the tumor including cavernous, capillary or mixed.^[3]

Circumscribed choroidal hemangioma typically appears as orange-red, round or oval, elevated mass posterior to the equator.[4] Lesions are usually solitary and unilateral, although bilateral choroidal hemangiomas have been reported.[5] The color of this tumor has been described as “salmon-colored”, “yellow-white”,[6] and “grayish-pink”.[3] Since the color of choroidal hemangiomaand the surrounding choroidare similar, it may be difficult to differentiate on color photographs, and the choroidal elevation may be moreapparent on clinical examination.Hemangioma can compress the surrounding choroid imparting a slight brown ring around its margin.[6]Pigmentary changes and accumulation of lipofuscin pigment (orange pigment) over the lesion have been reported.[7]   In the largest published series of 200 patients by Shields et al the most common reported symptom was blurred vision in up to 81% of patients, while some patients noted visual field defects, metamorphopsia and floaters. At initial presentation, visual acuity ranged from 20/20 to 20/40 in 24% of subjects, was 20/200 or worse in 54% and 20/400 or worse in 34% of eyes.[1] In this series, 67% of tumors were in the macula, 34% were between the macula and the equator, and no tumor was anterior to the equator. Mean tumor diameter was 6.7 mm, and mean tumor thickness was 3.1 mm. Serous retinal detachment and cystoid macular edema were reported in 81% and 17% of patients, respectively. Epiretinalmembrane,subretinal hemorrhage and exudates, total retinal detachment and Neovascularizationof iris and angle have also been reported.[1] NATURAL COURSE These lesions usually remain stationary in size, although there are reports of gradually progressive enlargement.[8,9] Slight enlargement with mean increase of 1.6 × 1.5 mm in basal diameter and 0.9 mm in thickness during an average period of 52 months was reported in five cases.[9] Vascular congestion of tumor vessels may lead to significant enlargement in tumor size.[10]

TREATMENT OPTIONS

Observation alone may be indicated in cases of asymptomatic hemangiomas demonstrating no subretinalfluid and also in subfoveal tumors which have resulted in hyperopic amblyopia.[1] Hemangiomas with advanced visual deficits and minimal anticipated visual potential may also be observed but one should consider that progressive subretinalfluid may lead to neovascular glaucoma and ultimately the need for enucleation.

There are different treatments for symptomatic serous retinal detachment associated with choroidal hemangiomas including photodynamic therapy (PDT), plaque brachytherapy, external beam and proton beam radiation, stereotactic radiosurgery, transpupillary thermotherapy, laser photocoagulation, oral propranolol and anti‐VEGF injections. 

Transpupillary Thermotherapy

Transpupillary thermotherapy (TTT) utilizes 810 nm diode laser with a large spot size and long exposure time leading to increased temperature and irreversible cytotoxic effect, sclerosis of vascular channels and partial or complete tumor regression in many patients.^[11] The use of TTT is limited to extrafoveal post‐equatorial circumscribed choroidal hemangiomas with shallow subretinalfluid with basal tumor diameter <10 mm and tumor thickness <4 mm.^[11,12] If the tumor margin touches the optic disc, TTT is not a proper treatment as it may induce thermal papillitis.^[13] TTT leads to tumor regression in many patients (42%, complete and 53%, partial regression), however it carries a risk of cystoid macular edema, preretinalfibrosis, focal iris atrophy and retinal vascular occlusion.^[11]Gunduz found that all tumors ceased leaking following TTT along with resolution of subretinalfluid. Visual acuity improved by two or more Snellen lines in 77% of eyes and remained unchanged in 23%.^[11]Indocyanine green dye can be injected before TTT to enhance heat uptake.^[14] Few authors believe that tumors larger than 10 mm in diameter and thicker than 4 mm may respond to TTT.^[15]

Patients and Methods

All patients with circumscribed choroidal hemangioma treated with transpupillary thermotherapy were included in our retrospective interventional case series. The study period ranged from January 2011 to December 2015 and a total of 27eyes(27 subjects) were included.

Inclusion:

Patients complaining of diminution of vision attributable to the tumor were included in the study.

Exclusion:

The patients who underwent prior treatment with TTT or PDT, those with pre-existing retinal vasculopathies and those with questionable diagnosis were excluded from the study.

Methods:

Medical records of the patients were thoroughly examined and patient data included age, sex, visual symptoms, and visual acuity (VA) at the initial visit and final visit. The tumour location and its position relative to fovea and optic disc was noted through indirect ophthalmoscopy. Tumor dimensions which included the largest horizontal diameter, largest vertical diameter and tumour thickness, were documented by ultrasound a and b scan.

The diagnosis of choroidal haemangioma was based on clinical characteristics, ultrasonography, optical coherence tomography and fundus fluorescein angiography when deemed necessary.

All the cases were treated by 2 senior consultants with a combined clinical experience of over 20 years in the field. The patients were treated with infrared diode laser (810nm) which was adapted on a Haag Strait slit lamp biomicroscope and delivered through a Mainster lens.

Purpose:

Purpose  of treatment was resorption of subretinal fluid over the tumor and not destruction of the lesion. The treatment parameters noted in each sitting included spot size, number of shots and exposure time. Follow up examinations were carried out by the same clinician and re-treatment was based upon the clinical response.

 Results

In our series of 27 cases, the mean age of the patients was 41.2 14 years (range: 14-75 years) with a slight male preponderance (M: F= 3.5:1).  All the cases were unilateral wherein the right eye was affected twice as often as the left. Patients consulted our center with the complaints of diminution of vision with a median duration of 6 months. Other complaints noted were pain, blurring of vision, metamorphopsia and floaters. At the initial presentation only 37% cases were referred with a diagnosis of choroidal hemangioma (Table 1).

The mean duration of follow up was 20.9 months (Range: 3.1- 61 months).

The location of the tumor with respect to the optic disc did not alter the visual outcome post treatment. In none of the cases did the tumor extend beyond the equator (Table 2).

In 8 (29.6%) patients the tumour had a subfoveal extension. Exudative retinal detachment was observed in 8 (29.6%) cases. Tumor dimensions measured by ultrasonography b scan were as follows: thickness (median: 3.4 mm, range: 1.5-5.8mm); horizontal diameter (median: 7.6mm, range: 2.7-12mm); vertical diameter (median: 7.3mm, range: 3.1-13.6mm).

The treatment parameters were as follows: median spot size of 1.2 mm, power of 250 mW and exposure time of 3 minutes. A mean of 2.7 sessions of TTT per tumour was needed in the study group.

The mean post-treatment VA was significantly lesser than pre-treatment VA (p value <0.0001). Vision either improved or maintained in 66% of the patients (18 out of 27) whereas it worsened in 33% (9 out of 27). 

1)On comparing the post treatment visual outcomes of the two groups viz. tumours involving the fovea and those not involving the fovea, difference was not statistically significant. The mean visual acuity was maintained at approximately 6/30 post-treatment in tumors not involving the fovea (p value – 0.69). The mean visual acuity in the tumors involving the fovea decreased from 6/38 to 6/28 post treatment (p value – 0.67).

2)In 7 of the 27 cases in whom the largest tumor dimension exceeded 10 mm, the post TTT visual acuity was stable or improved by 2 or more lines, in 57.2 % of the cases.

Whereas in cases with tumor size less than 10 mm, 73.7% cases had stable vision or improved by 2 or more lines (p value = 0.714).

3)In 9 of the 27 cases in whom the tumor thickness was greater than 4mm, the post TTT visual acuity was stable or improved by 2 or more lines, in 66.6% cases. Whereas in cases with tumor thickness less than 4 mm, the visual acuity was stable or improved by 2 or more lines in 72.3% cases (p value – 0.858).

Thus neither the tumor size nor the thickness was statistically significant in altering the final visual outcome post TTT in these patients. (Table 4) 

The mean visual acuity post TTT in patients presenting within 6 months of onset of symptoms was 6/24. The mean visual acuity post TTT in patients presenting 6 months after onset of symptoms was 6/32.

Four patients were switched to PDT due to non-response to treatment or increase in subretinal fluid. One patient was lost to follow up after 2 sessions of TTT when he maintained the visual acuity of 6/18. Two years later patient returned to the clinic with a drop in vision to 1/60 along with subretinal fluid on OCT. We suspect this to be a case of recurrence.

Discussion

Management of circumscribed choroidal hemangiomas is based on the severity of symptoms. While asymptomatic cases are best observed at a 6 monthly interval, the symptoms are secondary to the accumulation of subretinal fluid and exudative macular detachment. TTT can be an effective management option.^[16,17,18] There has, however, been reluctance to treat parafoveal or juxtapapillary tumors in an effort to preserve VA.^[11,16,19]

The parameters for treating CCH with TTT have been devised from the treatment effects on choroidal tumors mainly melanomas. Since TTT aims at producing hyperthermia at the level of RPE and choroid, the objective of the treatment is to achieve resolution of subretinal fluid rather than complete destruction of the tumour. The desired effects were observed with an increase in power (800-1000 mw) and prolonged exposure time (2-6mins) compared to that used in melanomas.

Our experience suggests that TTT is effective in reducing tumor thickness and serous fluid, in aiding tumor regression, and in preventing tumor recurrence. Although not statistically demonstrated, distance from the foveola or the optic nerve was not predictive of poor post-treatment VA.

Gill et al found 36% of the referred cases to be misdiagnosed^[20]. Shields et al reported only 29% cases with correct diagnosis of choroidal hemangioma before referral. In our study as well, only 37% cases were accurately diagnosed as CCH before referral, whereas the most common misdiagnosis was that of choroidal melanoma (18.5%).

Mashayekhi et al reported that the location of the tumour relative to the fovea had a significant role in the final visual outcome^[21]. In our study, among the tumours involving the fovea, although the visual acuity decreased from 6/28 to 6/38 post TTT, the decline was not statistically significant. Studies from Rishi et al and Gunduz et al showed that subfoveal tumours could maintain theirvision if the extrafoveal parts of the tumour were treated with TTT^[15]. Anand et al stated that the location of the tumour and duration of symptoms had an important role in the final visual outcome. Gill et al did not find an association between the distance of the tumor from the disc and fovea^[20].Even in our study we did not find any association between the distance of tumor and the final visual outcome.

Since TTT was found to be ineffective in melanomas larger than 10mm in diameter and more than 4mm in thickness, the same was hypothesized to be true for choroidal hemangiomas. Sharma et al believed that larger tumours and those with extensive bullous RD’s could respond to TTT. The possible reasons for its use could be: 1) The aim of the treatment is regression of subretinal fluid and not destruction of the tumour. 2) The fluid may gravitate while adopting a sitting position, thus TTT could be applied onto the tumour surface. 3) TTT could be applied away from the subfoveal and juxtapapillary parts of tumour^[22].

Tumour diameter and thickness did not play a role in altering the final visual outcome. Vision was stable or improved by 2 or more lines in 57.2% of cases with diameter larger than 10mm as opposed to 73.7% in those less than 10mm. In tumors thicker than 4 mm visual acuity was stable or improved by 2 or more lines, in 66.6% cases compared to 72.3% in tumor thickness less than 4 mm. Despite the small sample size, the dimensions of the tumour do not seem to alter the final visual outcome. Thus we cannot refute the possible role of TTT in larger tumours which were a relative contraindication earlier.

Although not clinically significant, the visual improvement was noted to be better in patients presenting within 6 months of onset of symptoms (6/36 to 6/24) as opposed to those presenting later than 6 months (6/35 to 6/32).

The cost of TTT per eye per session is $ 58.87 compared to PDT which costs $ 1417.5 per session. In a developing country like ours, where the per capita income is only $ 1861.5 and where the insurance infrastructure is so fragmented, the cost- benefit ratio still favours the application of TTT as a treatment modality. In patients who can afford, PDT can be the preferred treatment modality especially for sub-foveal tumours.

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Table 1

Diagnosis at presentation	Number (%)
Choroidal hemangioma	10 (37)
Choroidal melanoma	5 (18.5)
Central serous chorioretinopathy	4 (14.8)
Choroidal mass	1 (3.7)
Focal retinal detachment	1 (3.7)
Others	2 (7.4)
Undiagnosed	4 (14.8)

Table 2

Location	Number
Superotemporal to disc	7
Inferotemporal to disc	5
Temporal to disc	9
Nasal to disc	1
Superonasal to disc	3
Inferonasal to disc	1
Peripapillary	1

Table 3 

	Pre- TTT VA	Post-TTT VA
Better than 6/18	13 (48.2%)	11 (40.7%)
6/18 – 6/60	5 (18.5%)	8 (29.6%)
Worse than 6/60	9 (33.3%)	8 (29.6%)

Table 4 

Parameters	Category	Pre-TTT VA	Post-TTT VA	p value
		Mean	Mean
Largest tumor diameter	<10 mm	0.71 (6/30)	0.68 (6/28)	0.78
	>10 mm	0.78 (6/36)	0.59 (6/23)	0.69
Tumor  thickness	<4 mm	0.63 (6/25)	0.65 (6/27)	0.69
	>4 mm	0.96 (6/55)	0.72 (6/32)	0.21
Involvement of fovea	Absent	0.72 (6/32)	0.67 (6/28)	0.69
	Present	0.80 (6/38)	0.68 (6/28)	0.67
Duration of symptoms	<  6 months	0.77 (6/36)	0.61 (6/24)	0.44
	≥ 6 months	0.76 (6/35)	0.73 (6/32)	0.78