Russian Journal of Clinical Ophthalmology
ISSN 2311-7729 (Print), 2619-1571 (Online)

Circumscribed choroidal hemangioma: clinical course and treatment

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DOI: 10.32364/2311-7729-2020-20-2-56-62

A.F. Brovkina1, A.S. Stoyukhina2, I.V. Musatkina3

1Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation

2Scientific Research Institute of Eye Diseases, Moscow, Russian Federation

3Moscow City Ophthalmological Center of S.P. Botkin City Clinical Hospital, Moscow, Russian Federation

Background: choroidal hemangioma can present as either diffuse or circumscribed. Diffuse choroidal hemangioma has no well-defined borders being localized in the posterior part of the choroid and extending into the pre-equatorial zone. Circumscribed choroidal hemangioma has well-defined borders and have much in common with melanocytic and metastatic tumors.

Aim: to determine management strategy of circumscribed choroidal hemangioma (CCH).

Patients and Methods: 76 patients with CCH were examined. Clinical presentations and OCT findings and their changes over time were assessed in 41 patients aged 31–83 years (mean age 51.0±2.22 years). CCH sizes were as follows: prominence 0.8–4.0 mm (on average, 2.27±0.13 mm), diameter 2.64–14.0 mm (on average, 7.49±0.42 mm). Retrospective study of the outcomes of prior brachytherapy in 35 patients (median age 36.34 years) was performed. Before brachytherapy, median prominence of CCH was 3.47 mm and maxi mum diameter 10.6 mm.

Results: CCH was diagnosed accidentally in a half of the patients (51.2%). The tumors were predominantly localized in the macula and paramacular area (48 eyes), less common in juxtapapillary area (16 eyes), and the nasal half of the fundus (12 eyes). Complete resorption of subretinal fluid and tumor was reported in 18 eyes. In one eye (tumor prominence 4.25 mm, retinal detachment, and low vision for 8 years), the outcome of brachytherapy was poor. Radiation maculopathy has developed in 8 patients (22.86%) with CCH near the macula.

Conclusion: CCH is a torpid benign choroidal tumor with good vision at baseline which requires dynamic follow-up and OCT to monitor retina, retinal detachment height, and tumor thickness. Progressive loss of vision and progressive retinal detachment are considered indications for treatment. Asymptomatic or non-progressive CCHs require careful dynamic follow-up only.

Keywords: choroid, circumscribed choroidal hemangioma, op tical coherence tomography, brachytherapy, clinical signs.

For citation: Brovkina A.F., Stoyukhina A.S., Musatkina I.V. Circumscribed choroidal hemangioma: clinical course and treatment. Russian Journal of Clinical Ophthalmology. 2020;20(2):56–62. DOI: 10.32364/2311-7729-2020-20-2-56-62.


Background

Choroidal hemangioma (CH) belonging to hamartomas is characterized by benign tumor signs, i.e., torpid growth and long-term asymptomatic period. No published data on CH prevalence are available. Some authors report on CH prevalence in enucleated eyes (0.76%) [1].

Hemangiomas are classified into three morphological types, i.e., cavernous, capillary, and mixed. Cavernous hemangioma (major type of hemangiomas in the choroid) is composed of large thin-walled blood vessels lined by flat endothelial cells and separated by thin intervascular septums [1]. Capillary hemangioma is generally found in the retina.

CH can present as either diffuse or circumscribed. Diffuse CH has no well-defined borders being localized in the posterior part of the choroid and extending into the pre-equatorial zone. Bright reddish orange reflex (significantly different from that of the fellow eye) is created with retroillumination. Echograms demonstrate diffuse choroidal thickening. Diffuse CH can be associated with Sturge-Weber syndrome and is commonly diagnosed in younger patients.

Circumscribed CH (CCH) is a more common type [2]. In contrast to diffuse CHs that are associated with phacomatoses, CCH is not related to systemic disorders.

CCH has well-defined borders and much in common with melanocytic and metastatic tumors. CCH is a benign tumor; nevertheless, it results in total blindness in a half of these patients due to secondary retinal changes [3].

The desire to preserve vision in these eyes resulted in the use of virtually all methods to destroy choroidal melanoma.

Xenon photocoagulation over the whole surface of the tumor was applied since 1970s to limit the spread of retinal detachment and to reduce CCH size. The result was partial or, occasionally, complete resolution of subretinal fluid while tumor size remained the same. In the late 1970s, argon-laser photocoagulation became more popular. Circular retinal laser photocoagulation was performed along tumor margins to limit the spread of retinal detachment, or, alternatively, coagulation of tumor blood vessels was performed [3, 4]. Over the last two decades, transpupillary thermotherapy (TTT) and photodynamic therapy (PDT) are used [6]. However, the effectiveness of tumor coagulation by TTT depends on its thickness but also the presence of pigment and the absence of subretinal fluid [7]. As more experience is gained, published data on adverse events of TTT (i.e., branch retinal vein occlusion with hemorrhages behind chorioretinal scar, rigid pupil due to pupillary ruff burn, secondary macular scars etc.) become available [8]. PDT results in long-term intraretinal microcystic edema and/or neurosensory retinal detachment [9] and choroidal neovascular membrane [10]. The lack of the effect of coagulation accounted for the use of radiotherapy. Proton beam efficacy was first reported in the late 1990s [11]. Radiotherapy provides positive effects (i.e., resolution of subretinal fluid, reduced CCH size) but results in late complications as well [12]. Radiation neuropathy and maculopathy were diagnosed in 42% while dry eye and radiation cataract were diagnosed in 20% [12]. Attempts were also made to treat CH using stereotaxic surgery techniques [13]. The experience of radiotherapy for CCH is limited; however, predominant view is that the above-mentioned types of radiotherapy should be recommended as adjuvant treatment for CCH after laser photocoagulation and PDT [12, 13]. Brachytherapy was implemented for eyes with extensive exudative retinal detachment above CCH or juxtapapillary CCH when TTT and PDT could not be done [14]. Radiation was performed using eye applicators with γ-ray sources. Every second or third patient developed radiation retinopathy or optic neuropathy after brachytherapy [7]. Therapeutic methods to destroy CCH (intravitreal bevacizumab or peroral propranolol) failed to demonstrate any effects [15, 16].

As a result, there is an ongoing debate on the treatment for CCH.

The aim of this study is to determine management strategy for CCH. 

Patients and Methods

76 patients with CCH were divided in two groups, i.e., naïve patients and patients with prior treatment.

Clinical presentations and optical coherence tomography (OCT) findings and their changes over time were assessed in 41 patients (27 women and 14 men) aged 31-83 years (mean age 51.0 ± 2.22 years). Follow-up period was 1 to 14 years (median 5 years). CCH sizes measured at the primary visit were as follows: prominence 0.8-4.0 mm (on average, 2.27 ± 0.13 mm), diameter 2.64-14.0 mm (on average, 7.49 ± 0.42 mm). Time from symptom onset to CCH diagnosis is summarized in Table 1.

Таблица 1. Сроки выявления гемангиомы хориоидеи от момента появления первых признаков нарушения зрительных функций Table 1. Time to choroidal hemangioma diagnosis from the onset of early signs of visual impairment

CCH was found in the macula or paramacular area in 37 eyes, juxtapapillary area in 2 eyes, and in the nasal half of the retina in 2 eyes.

Enhanced depth imaging (EDI) OCT was performed using the OCT SPECTRALIS® system (Heidelberg Engineering, Heidelberg, Germany). EDI-OCT provides more detailed imaging of Bruch’s membrane and choriocapillaries. Grayscale images that are more informative were analyzed. The distance between the outer margin of retinal pigment epithelium (RPE) and hyperreflective line outside the layer of large choroid blood vessels (that is believed to be a border between choroid and sclera) was considered choroid complex [17].

In group 2, the outcomes of prior brachytherapy in 35 patients (median age 36.34 years) were retrospectively studied. The outcomes were assessed after 18-24 months. Before brachytherapy, median prominence of CCH was 3.47 mm and maximum diameter 10.6 mm. CCH was found in the juxtapapillary area in 14 eyes, paramacular area in 11 eyes, and the nasal and upper half of the retina in 10 eyes.

CCH diagnosis was verified by ophthalmoscopy, fundus photography, fluorescent angiography (FAG), and OCT. CCH and their dynamic changes were evaluated by ocular ultrasonography. Brachytherapy (1 course) was performed using domestically-produced radioactive ruthenium eye applicators.

Statistical analysis was performed using IBM SPSS Statistics 23.0 software.

Results & Discussion

In both groups (n = 76), CCH signs were revealed in the 4th-5th decades of life (31-83 years). This is similar to the published data [3]. There were slightly more women than men (1.24:1). Meanwhile, no gender differences in patients with CCH [18] or the prevalence of men over women [6] were reported. Given that C.L. Shields et al. observed the largest number of CCH patients (n = 200) [18], it should be accepted that gender differences have no role in verified CCH diagnosis.

Time to diagnosis, i.e., the interval from first alert symptoms (visual impairments) to CCH diagnosis, is summarized in Table 1. CCH was diagnosed accidentally (when determining reading glasses lens strength or in the course of ocular check-up) in a half of the patients (51.2%). A little more than one-third of the patients complained of poor vision 2-3 weeks before visiting an ophthalmologist. In a half of the patients, CCH duration was less than a year.

In general, in 75 out of 76 CCH patients, the tumor was unilateral and monofocal and predominantly affected central area of eye fundus (see Table 2). 1 patient was diagnosed with diffuse CH and Sturge-Weber syndrome in early childhood. At the age of 8 years, a solitary CCH was identified.

Таблица 2. Распределение гемангиом хориоидеи с учетом локализации Table 2. Choroidal hemangioma localizations

By the time of verified diagnosis, maximum CCH prominence and diameter were 4.2 mm and 14 mm, respectively. Median follow-up period was 5 years (1-14 years). Earlier and recent published data demonstrate that by the time of verified diagnosis CCH prominence and diameter are 1-8 mm and 3-19 mm, respectively [18].

CCHs are characterized by typical fundoscopic findings. CCH is presented as red (see Fig. 1A) or sometimes yellowish (see Fig. 1B) rounded or elliptical tumor with smooth surface. As CCH progresses, gray-whitish focuses may appear (see Fig. 2).

Рис. 1. Фото глазного дна: A – больная Е., 37 лет, соб- ственные сосуды опухоли придают красную окраску; B – больная Г., 62 года, опухоль окрашена желтоватым цветом за счет изменений в надлежащей сетчатке Fig. 1. A – fundus imaging of a 37-year-old woman

Рис. 2. Фото глазного дна пациента П., 33 года, на мо- мент случайного выявления ОГХ (A) и через 27 мес. (B), стрелка – участки беловато-серого цвета Fig. 2. Fundus imaging of a 33-year-old man at the time of accidental diagnosis of CCH (A) and 27 months

Small CCHs have rather sharp borders. This stage is characterized by little subretinal fluid accumulation and filigree pattern (see Fig. 3) due to cystoid retinal degeneration. In 13 eyes (17.1%), the tumor was dark-red-colored as a result of ongoing pathological process in the overlying retina (reactive metaplasia of RPE; see Fig. 4). Pigmented area around CCH found in some eyes is probably accounted for by the compression of choroidal melanocytes along tumor margin (see Fig. 5) [2].

Рис. 3. Фото глазного дна пациентки Д., 38 лет: геман- гиома хориоидеи, симптом «ажурности» за счет кисто- образования в надлежащей сетчатке, более выраженный в верхненаружной половине опухоли Fig. 3. Fundus imaging of a 38-year-old woman: choroidal heman

Рис. 4. Фото глазного дна (A) и горизонтальный ОКТ-срез через опухоль (B) и зону атрофии книзу от опухоли (C) па- циентки И., 49 лет. Гемангиома хориоидеи темно-аспидного цвета. Синие стрелки – утолщение пигментного эпителия, зеленые стрелки – сохранный х

Рис. 5. Фото глазного дна (A) и горизонтальный ОКТ-срез через опухоль (B) пациента А., 45 лет. Стрелки – зона пигментации по краю гемангиомы, зона компрессии хориокапилляров Fig. 5. Fundus imaging (A) and horizontal OCT cross-sectional image of the tumor

In 6 patients with visual complaints for less than a month (2 eyes), 12 months (3 eyes), or 12 years (1 eye), CCH was complicated by extensive retinal detachment.

М. Furuta et al. report that stable overlying subretinal fluid results in neurosensory retinal lesions when CCH persists for 3 months or more [19].

In 10 eyes, chorioretinal atrophy with surface pigmentary focuses was identified around the tumor. These areas are choriocapillary atrophy and hyperreflective lesions in the overlying Bruch’s membrane and the outer retina as demonstrated by OCT (see Fig. 4).

Visual impairment in CCH is characterized by hyperopic shift without any lesion of the overlying retina [20] or, alternatively, progressive blurred vision or sudden vision loss resulting from secondary retinal changes [2].

In 9 eyes, hyperopic shift due to the prominent CCH was 0.5 D to 1.5 D (on average, 0.83 ± 0.13 D) as compared with the fellow eye. Best-corrected visual acuity (BCVA) ranged from 20/67 to 20/20 (on average, 0.66 ± 0.07). Mean CCH prominence was 1.79 ± 0.24 mm. In all patients, hyperopic shift was associated with outer retinal changes (as demonstrated by OCT).

Among the patients with central CCHs (n = 29), low vision (0.45 ± 0.07) was reported in 19 eyes. In 11 out of 19 eyes, subfoveal neurosensory retinal detachment was diagnosed. In 8 eyes, foveal photoreceptor damage (edema or atrophy) associated with nuclear layer edema or cystic macular lesions were identified.

Biometric parameters of CCH in patients with good (20/20) and low vision were similar, i.e., mean prominence was 2.06 ± 0.2 mm and 2.21 ± 0.18 mm, respectively (p = 0.14) and mean diameter was 7.15 ± 0.76 mm and 7.09 ± 0.51 mm, respectively (p = 0.53). Direct correlation between BCVA and the distance between CCH margin and fovea (r = 0.43, p = 0.03) was revealed, i.e., in eyes with low vision, CCHs were located significantly closer (by 1308.71 ± 417.69 μm) to the fovea (p = 0.03).

Therefore, in central CCHs, tumor prominence is similar in patients with good and low vision (p = 0.72). In eyes with low vision, subfoveal retinal detachment whose height correlated with CCH prominence (r = 0,39, p = 0.02) and diameter (r = 0.45, p = 0.01) was diagnosed.

CCHs are rather often diagnosed as an incidental finding (50.1% among our patients). In 11 patients with macular CCHs (in 2 out of 11 patients, CCH was located directly under the fovea), visual acuity was 20/20 over the whole follow-up period (1-12 years, median 5 years). Retinal morphological changes (i.e., cystic degeneration) are believed to occur in CCH prominence ≥ 1.8 mm. Retinal edema occurs in even greater CCH prominence [5]. Meanwhile, some authors report on CCHs presenting as a dome-shaped choroidal elevation with focal hyperplasia of the overlying RPE and exudative retinal detachment above the tumor in uncompromised retinal anatomy and photoreceptor layer [21]. Our findings demonstrate that nuclear layer edema and cystic degeneration occur in CCH prominence ≥ 1.34 mm and ≥ 1.65 mm, respectively. Moreover, nuclear layer edema precedes cystic degeneration (see Fig. 6).

Рис. 6. Горизонтальный ОКТ-срез через фовеолярную зону и гемангиому хориоидеи в динамике с интервалом между исследованиями 18 (B), 27 (C) и 33 (D) мес. от исходного исследования (A). Четко прослеживается возникнове- ние многочисленных прогрессирующих кист

Visual acuity decreases when microcystic macular edema or neurosensory retinal detachment occur [6, 22].

Our findings demonstrate that central CCHs were associated with reduced BCVA (on average, 0.48 ± 0.08) in 15 eyes. However, subfoveal neurosensory retinal detachment was revealed only in 9 eyes. In 6 eyes, tumor margin was located in the foveal area; photoreceptor layer edema and edema or cystic degeneration of nuclear layers of the overlying retina were detected. In 2 eyes, photoreceptor layer atrophy (that accounted for low vision) was identified.

In 1 eye, BCVA was stable over a 2.5-year period. During the follow-up, foveal nuclear layer edema and progressive parafoveal cystic degeneration were reported. Later on, this patient experienced subfoveal neurosensory retinal detachment and progressive cystoid edema extending to the fovea (see Fig. 6).

This case explains fluctuations in visual disturbances that are typical of some CCH patients. Stable visual impairment occurs in severe photoreceptor destruction and significant cystic degeneration of the overlying retina.

Is there any correlation between CCH prominence and abnormalities of the overlying retina? In 11 patients with incidental CCH and mean tumor prominence 2.13 mm (0.8-3.6 mm), visual acuity was stable (20/20) over a mean follow-up period of 4.46 years (1-12 years). Meanwhile, in 10 patients who complained about vision loss, mean CCH prominence was 2.34 mm (0.83-4.2 mm). In these patients, initial vision loss was reported, on average, 3.6 years (1-9 years) before visiting an ophthalmologist. In general, CCH was located in the paramacular area extending to the macula (17 eyes), directly under the fovea (2 eyes), or juxtapapillary above the optic disc. No significant difference in CCH prominence between the groups with good and low vision was revealed (p = 0.72).

CCH is known to begin its growth in the outer choroid [1]. The specificity of blood flow accounts for the exudation of blood components and retinal edema in CCH. OCT angiography (OCTA) demonstrates peculiar vascular pattern characterized by irregularly dilated large blood vessels [23] and preserved choriocapillary layer [24]. Previous studies on CCH own vessels have shown that their diameter is 2.5 to 5 times greater than the diameter of contralateral normal choroidal vessels while CCH blood flow is slower as compared with other choroidal tumors [25]. CCHs can be considered the tumors with passive blood flow that is similar to cerebral hemangiomas with slow blood flow [26, 27]. These specificities of CCH blood flow account for the exudation of blood components and retinal edema. This process is generally sluggish.

The outcome of progressively growing CCH is a complete retinal detachment and total vision loss. Published data demonstrate that CCH treatment is still controversial as baseline tumor size, its localization, and therapeutic methods that are familiar to the attending ophthalmologist are important. However, it was demonstrated as early as 1997 that brachytherapy is effective in terms of the resolution of subretinal fluid [28]. Additional decrease in tumor prominence (on average, by 50%) was observed after one course of radiotherapy when using eye applicators with γ-ray sources [4].

Considering our experience with brachytherapy for choroidal tumors (including CCH), we retrospectively analyzed the efficacy of one course of radiotherapy in 35 patients with CCH (follow-up was 18-24 months). At baseline, maximum CCH prominence and diameter were 4.5 mm (median 3.47 mm) and 10.6 mm, respectively. CCH was predominantly found in the juxtapapillary area in 40% and, less common, in the paramacular area (31.43%) and the nasal half of retina (28.57%). At baseline, visual acuity was poor in 10 eyes with central CCH localization and 7 eyes with juxtapapillary localization (at the superior temporal margin of the optic disc). In the remaining 18 eyes, visual acuity was good (20/25 to 20/20). Brachytherapy outcomes were evaluated by the resolution of subretinal fluid and CCH status. Complete resolution of subretinal fluid and CCH (tumor regression into a flat chorioretinal scar) was observed in 18 eyes within 12-16 months. One year after brachytherapy, complete resolution of subretinal fluid and two-fold decrease in CCH prominence (as compared with baseline measurements) were detected in 16 eyes. Positive effect persisted for 18-24 months (median 22 months). In one eye with CCH prominence 4.25 mm, extensive retinal detachment, and significant vision loss for 8 years, the outcome of brachytherapy was poor. Others authors also report on reduced tumor prominence as a result of its partial regression after brachytherapy [14]. Complete or partial CCH resorption is possible due to the decreased blood flow in new tumor vessels or, alternatively, due to radiation injury of vascular endothelium followed by complete vascular occlusion. These findings are supported by OCTA studies that demonstrate significant decrease in CCH vessel area and blood flow one year after brachytherapy [29]. Despite rather fast resolution of subretinal fluid and retinal reattachment, persistent CCH (including residual tumor) often results in recurrent retinal detachment [28]. Both TTT and brachytherapy may have late complications [30], e.g., radiation retinopathy (24%), radiation papillopathy (5%), and subretinal fibrosis (10%) [31]. These complications generally occur almost 2 years after radiotherapy [14]. In our case series, radiation maculopathy developed in 8 patients (22.86%) with CCH located near the macula. High occurrence of maculopathy after brachytherapy for any central tumor is easy to explain since the diameter of the macular area to be preserved in paramacular CCHs is small (just 500 μm) [32]. Therefore, this complication should be considered the expected one.

The question then arises as to if and when to treat CCHs? G.D. Lewis et al. suggest that long-term observation and vision loss before treatment starts are prognostic factors of poor visual outcome [8]. It is difficult to argue considering destructive changes of the overlying retina identified by OCT. Meanwhile, our findings demonstrate that even in macular CCHs BCVA may be good for a long time, e.g., in 11 patients, BCVA was 20/20 over the long-term period (median follow-up 5 years). In a half of patients who presented with complaints of low vision (n = 11), CCH was diagnosed at the first appointment while the duration of low vision (20/33 to 20/29) was less than a year. An explanation can be found in scientific literature: foveal and macular CCHs can be asymptomatic for a long time even in retinal changes because of very slow tumor growth [24].

Conclusion

CCH is a torpid benign choroidal tumor with good vision at baseline which requires dynamic follow-up and OCT to monitor retina, retinal detachment height, and tumor prominence. Progressive vision loss and progressive retinal detachment are considered indications for treatment. Asymptomatic or non-progressive CCHs require careful dynamic follow-up only. Patients should be instructed to perform a self-monitoring test for central vision between appointments.



About the authors:
1Alevtina F. Brovkina — MD, PhD, Professor, Full Member of the Russian Academy of Sciences, ORCID iD 0000-0001-6870-1952;

2Alevtina S. Stoyukhina — MD, PhD, Senior Researcher of the Division of the Pathology of Retina and Optic Nerve, ORCID iD 0000-0002-4517-0324;

3Irina V. Musatkina — MD, PhD, ophthalmologist of the Department of Ophthalmic Oncology, ORCID iD 0000-0002-2012-5105.

1Russian Medical Academy of Continuous Professional Education. 2/1, Barrikadnaya str., Moscow, 125993, Russian Fede­ration.

2Scientific Research Institute of Eye Diseases. 11A, Rossolimo str., Moscow, 119021, Russian Federation.

3Moscow City Ophthalmological Center of S.P. Botkin City Clinical Hospital. 5, 2nd Botkinskiy passage, Moscow, 125284, Russian Federation.

Contact information: Alevtina S. Stoyukhina, e-mail: a.stoyukhina@yandex.ru

Financial Disclosure: no authors have a financial or property interest in any material or method mentioned. There is no conflict of interests. Received 13.03.2020. 



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