Diffuse Choroidal Hemangioma in Sturge-Weber Syndrome: Correlation between Clinical Features, Imaging, and Treatment Response

Abstract

Introduction

The aim of this study was to describe the clinical features, multimodal imaging characteristics, treatment outcomes, and prognostic factors in patients with diffuse choroidal hemangioma (DCH) associated with Sturge-Weber syndrome (SWS)/phakomatosis pigmentovascularis (PPV) at a referral center in India.

Methods

A retrospective observational study was conducted between 2013 and 2024 on patients diagnosed with SWS/PPV and associated DCH. A poor outcome was defined as a final best-corrected visual acuity (BCVA) of 20/200, persistent or recurrent exudative retinal detachment, persistent tumor, or disease recurrence.

Results

A total of 29 patients (32 eyes) with SWS/PPV-associated DCH were included. The mean age at presentation was 25.3 ± 11.6 years, with a female predominance (59%). Most patients had SWS (90%), while 10% had PPV. Exudative retinal detachment and glaucoma were observed in 46% and 31% of SWS eyes, and 66% and 83% of PPV eyes, respectively. The mean tumor basal diameter and thickness were 8.31 mm and 4.16 mm at presentation. Selected cases were managed with plaque brachytherapy, trabeculectomy, external beam radiotherapy, or intravitreal anti-VEGF injections. Complete tumor regression was achieved in 22% of eyes. Mean BCVA improved significantly from 20/1200 to 20/160 at final follow-up; however, a poor visual outcome occurred in 69% of eyes. On multivariate analysis, persistent tumor (p = 0.008) and tumor recurrence (p = 0.03) were independent predictors of poor outcome.

Conclusion

DCH in SWS is a vision-threatening condition requiring individualized multimodal treatment. Although anatomical and visual improvement is achievable, recurrence and tumor persistence are common and predict poor outcomes. Thus, long-term follow-up and early intervention are critical for optimal management.

Introduction

Sturge-Weber syndrome (SWS) is a rare, sporadic neuro-oculocutaneous disorder with an estimated incidence of approximately 1 in 50,000 live births. SWS is characterized by vascular malformations affecting the leptomeninges, face, and eye [1]. SWS is traditionally described as a triad of ipsilateral leptomeningeal angiomatosis, facial port-wine stain (nevus flammeus), and congenital glaucoma; however, the current diagnostic criteria allow for the diagnosis of SWS when any two of these features are present [2, 3]. SWS arises from a somatic mutation in the GNAQ gene and is not inherited, unlike other phakomatoses with hereditary transmission [4].

Ocular involvement occurs in >50% of patients with SWS and often manifests as glaucoma that can be congenital/neonatal onset due to angle anomaly, secondary open-angle glaucoma in the teen years and associated diffuse choroidal hemangioma (DCH) [2]. Phakomatosis pigmentovascularis (PPV), in contrast, represents a coexistence of a capillary malformation with a pigmentary nevus (e.g., nevus of Ota, Mongolian spots, or dermal melanocytosis) [5]. PPV subtypes are classified based on the combination and distribution of vascular and pigmentary lesions, and systemic involvement may include ocular or neurological abnormalities. The condition is often bilateral (75%), and glaucoma is associated in 88% of the eyes. DCH is noted in 25% of the eyes [6, 7].

While SWS and PPV may overlap phenotypically especially in cases with both vascular and pigmentary lesions they are distinct entities in nosology. SWS is primarily a vascular neurocutaneous syndrome linked to GNAQ mutation, whereas PPV encompasses combined vascular-pigmentary mosaicism, often involving GNAQ or GNA11 mutations [8, 9]. Recognition of their molecular and clinical boundaries aids accurate diagnosis, prognostication, and genetic counseling. Recent literature stresses careful clinical assessment to distinguish SWS from PPV when port-wine stains and pigmentary lesions coexist, as management, complications, and prognosis may differ [6].

DCH is a benign vascular tumor of the choroid that, unlike its circumscribed counterpart, typically occurs in the setting of systemic syndromes, such as SWS [10]. Circumscribed choroidal hemangiomas (CCHs) are localized, well-demarcated lesions with no systemic associations, whereas DCH presents as a diffuse, ill-defined thickening of the choroid, often involving the posterior pole and peripheral retina [2, 4, 11]. While CCH is usually diagnosed in adulthood, DCH often presents in childhood or infancy, thereby complicating early detection [1, 12].

Although DCH is histopathologically benign, it can result in serious visual impairment due to complications such as subretinal fluid (SRF) accumulation, cystoid macular edema, and exudative retinal detachment (ERD) [4, 13]. Diagnosing asymptomatic DCH can be challenging, particularly in children. Therefore, multimodal imaging is critical for early and accurate diagnosis. Swept-source optical coherence tomography (SS-OCT), fluorescein angiography, indocyanine green angiography, and B-scan ultrasonography (USG) provide complementary insights into the extent and nature of choroidal involvement [2, 14, 15].

DCH management aims to preserve vision and prevent irreversible retinal damage. Treatment modalities include photodynamic therapy, plaque brachytherapy, external beam radiotherapy (EBRT), and, in select cases, anti-VEGF agents or laser photocoagulation [4, 16–19]. The treatment choice depends on the extent of the lesion, visual impairment, and the presence of complications [4].

This study presents our institutional experience with DCH in SWS and PPV, focusing on its clinical features, multimodal imaging characteristics, and treatment responses. By correlating these parameters, we aim to improve diagnostic precision and optimize individualized management strategies for this challenging condition.

Methods

This retrospective observational study was conducted at LV Prasad Eye Institute, India, between 2013 and 2024. The study included patients diagnosed with SWS or PPV and associated DCH. The study was approved by the institutional review board, and it adhered to the tenets of the Declaration of Helsinki. Patients of any age and gender were included if they had a confirmed diagnosis of SWS or PPV with ocular involvement, particularly DCH. The diagnosis of SWS was based on the presence of at least two of the following classical triad features: facial port-wine staining, neuroimaging-confirmed leptomeningeal angiomatosis, and glaucoma or choroidal hemangioma. Patients with PPV were diagnosed based on characteristic features, such as congenital cutaneous vascular malformations (e.g., port-wine stain) alongside pigmented nevi (e.g., dermal melanocytosis), and presence of DCH. Patients with incomplete or poor-quality imaging records were excluded.

Demographic and clinical data, including age at presentation, gender, lesion laterality, cutaneous involvement, systemic involvement, history of seizures, and neurological abnormalities, were collected. Best-corrected visual acuity (BCVA) was recorded using the Snellen chart and later converted to logMAR for statistical analysis. A complete ocular examination was performed at presentation and all follow-up visits.

Imaging modalities, such as color fundus photography and fundus autofluorescence, were reviewed to collect information on the lesion’s morphology, including its size, color, and margins. Ultra-widefield retinal imaging using the OPTOS system was used for a detailed analysis of lesion distribution and associated retinal changes. ImageJ software was utilized to measure lesion size on fundus photographs, using the disc size as a reference for calibration. SS-OCT (DRI-OCT Triton Swept-source; Topcon, Tokyo, Japan) was utilized to obtain high-resolution cross-sectional images of the tumor and surrounding retina. The evaluation focused on retinal architecture, choroidal thickness, and the presence of subretinal or intraretinal fluid (IRF). B-scan USG (Sonomed B 3000; Sonomed Technology Inc., Lake Success, New York, NY, USA) was used to assess tumor thickness and echogenicity and to rule out other choroidal masses. Brain magnetic resonance imaging findings were reviewed for evidence of leptomeningeal enhancement, confirming neurological involvement in SWS.

In cases of bilateral involvement, each eye was analyzed independently. Tumor outlines were transcribed onto standardized retinal charts centered on the fovea when fundus drawings were available, allowing for visual representation of lesion distribution.

Treatment data, including the type of intervention, such as plaque brachytherapy, EBRT, intensity-modulated radiation therapy, intravitreal bevacizumab, oral propranolol, or observation, were recorded. A close observation was chosen, particularly for stable lesions with good visual acuity and no SRF. For glaucoma management, medical treatment with antiglaucoma medication or surgical management with trabeculectomy was performed. Treatment was individualized based on lesion extent, visual symptoms, presence of SRF, and overall ocular status.

A poor outcome was defined as the presence of one or more of the following at the final follow-up: BCVA worse than 20/200, persistent or recurrent ERD, documented recurrence of tumor activity, or failure of tumor to show regression on imaging. Intraocular pressure more than 21 mm of Hg was considered as a criteria for diagnosis of glaucoma.

All data were included in our statistical analysis when available; analysis for any given variable only included patients for whom information was known. Descriptive statistics were used to summarize demographic characteristics and imaging findings. Continuous variables were presented as mean, median, and range. Categorical variables were presented as counts and percentages. Two-tailed paired t-tests were used to compare tumor size, as measured during fundus photography. Snellen BCVA was converted to equivalent LogMAR for further analysis. Statistical significance was defined as p < 0.05, and all p values were 2-tailed. All statistical analyses were performed using SPSS (IBM, SPSS Statistics, Version 26; SPSS Inc., Chicago, IL, USA) software.

Results

This retrospective analysis included 29 patients diagnosed with DCH associated with SWS/PPV, contributing to 32 affected eyes (Table 1). In our cohort, 3 patients (10%) had PPV, while the remaining 26 patients (90%) had SWS. The cohort consisted of 17 females (59%) and 12 males (41%). The mean follow-up duration for the cohort was 82.2 months, with a median follow-up of 30 months. The most frequently affected age groups were 10–20 and 20–30 years (each, n = 8, 28%), followed by the 30–40 years group (n = 5, 17%). Four patients (14%) were younger than 10 years of age, and 2 patients (7%) were aged 50–60 years. None were older than 60 years. Unilateral involvement was more common in 26 patients (90%), whereas bilateral eye involvement occurred in 3 patients (10%), all of which were PPV cases. Eyelid involvement was more frequently observed in the right eye (18 eyes, 62%) than the left (14 eyes, 48.3%). All 32 affected eyes (100%) exhibited clinical signs of DCH.

Table 1.

Demographic and clinical characteristics of DCH in SWS and PPV

Characteristics	Variables	SWS, n (%)	PPV, n (%)
Patients, n	29 (32 eyes)	26 (26 eyes)	3 (6 eyes)
Patients with facial port-wine stain, n	​	20 (76)	2 (66)
Eyes with glaucoma, n	​	8 (31)	5 (83)
Eyes with exudative RD, n	​	12 (46)	4 (66)
Age, years	Mean, median, range	22.31, 22 (0–57)	27, 27 (18–36)
Gender	Male	9 (35)	3 (100)
	Female	17 (65)	0
Laterality	Unilateral	26 (90)	0
	Bilateral	0	3 (100)
Tumor size	Mean Diameter	8.31	7.62
	Thickness (on USG)	4.16	4.24
Tumor location	Peripapillary	2 (6)
	Macular	3 (9)
	Superior	4 (13)
	Inferior	3 (9)
	Diffuse	20 (63)
Tumor color	Orange	28 (88)
	Yellow	3 (9)
	Red	1 (3)
Ultrasonography	B-scan: acoustic solid	32 (100)
	A-scan: high internal reflectivity	32 (100)
OCT	SRF	4 (13)
	IRF	0 (0)
Treatment	Plaque brachytherapy	3 (10)
	EBRT	7 (24)
	Propranolol	2 (7)
	Observation	4 (14)

SWS, Sturge-Weber syndrome; PPV, phakomatosis pigmentovascularis; USG, ultrasonography; SRF, subretinal fluid; IRF, intraretinal fluid; EBRT, external beam radiotherapy; IMRT, intensity-modulated radiation therapy.

Ultrawidefield fundus photography most commonly demonstrated diffuse choroidal involvement in 20 eyes (63%). The mean largest tumor basal diameter at presentation was 8.31 mm (range, 6–22 mm), and the mean tumor thickness was 4.16 mm (range, 2–10 mm). SRF and IRF were each noted in 4 eyes. Serial imaging of 18 eyes measured with ultrasound that received treatment revealed tumor regression over time, with the mean basal diameter and mean thickness reducing to 6.64 and 3.31 mm, respectively, at the 3-month follow-up. At the final follow-up, further reduction was observed with a mean basal diameter of 4.33 mm and a mean thickness of 1.23 mm.

Plaque brachytherapy was most common (7 eyes, 24%), followed by radiation (EBRT/intensity-modulated radiation therapy) (5 eyes, 17%). Intravitreal bevacizumab was used in 3 eyes (10%) and oral propranolol in 2 eyes (7%). Four eyes (14%) were managed conservatively. Five patients (16%) were lost to follow-up, and 2 patients (6%) declined treatment despite counselling.

Following treatment (N = 21), tumor regression was documented in 7 eyes (22%), and tumor stability was maintained in another 7 eyes (22%). Among the 16 eyes presenting with ERD, resolution was achieved in 6 eyes (38%) with treatment. Recurrence of disease activity, characterized by renewed exudation or tumor progression, was observed in 6 eyes (19%) during follow-up. Visual outcomes showed notable improvement, with the mean BCVA improving from 20/1200 at presentation to 20/200 at the 3-month post-treatment visit, and further to 20/160 at the final follow-up, indicating sustained visual gains (Table 2).

Table 2.

Treatment outcome in patients with DCH

Parameter	Pre-treatment	Post-treatment	p value
BCVA (logMAR)	1.846	0.953	0.03
Mean IOP, mm Hg	20	17	0.02
Mean tumor basal diameter, mm	8.31	4.33	0.001
Mean tumor thickness, mm	4.16	1.23	0.001
Exudative RD	16	10	0.041

BCVA, best-corrected visual acuity; IOP, intraocular pressure; RD, retinal detachment.

Glaucoma was observed in 13 eyes (41%), including 8 eyes with SWS and 5 eyes with PPV, occurring either at presentation or during follow-up. Of these, surgical intervention in the form of trabeculectomy was required in 7 eyes (24.1%) due to inadequate intraocular pressure (IOP) control or advanced optic nerve damage. Topical anti-glaucoma medications were sufficient in 4 eyes (13.8%), and 2 eyes were monitored conservatively due to borderline IOP without optic nerve compromise.

Eyes were categorized into poor (n = 22, 69%) and good (n = 10, 31%) outcome groups based on the presence of one or more of the following: tumor recurrence, ERD, final BCVA worse than 20/200 or absence of tumor regression. Univariate analysis revealed that poor outcomes were significantly associated with the presence of facial port-wine stain (p = 0.04), non-regressed tumor response (p = 0.008), recurrence (p = 0.01), and ERD (p = 0.03) (Table 3). Multivariate logistic regression identified tumor non-regression (odds ratio [OR] 10.5; 95% confidence interval [CI], 1.8–60.7; p = 0.008) and recurrence (OR 7.8; 95% CI, 1.1–52.3; p = 0.03) as independent predictors of poor outcome. The presence of a facial stain showed a strong trend toward significance (OR 5.1; 95% CI, 0.9–28.4; p = 0.07). Illustrative case example of DCH in case of SWS pre and post treatment with radiation is shown in Figure 1.

Table 3.

Univariate analysis of factors associated with poor outcome and multivariate logistic regression for predictors of poor outcome in 32 eyes with DCH

Univariate analysis				Multivariate analysis
variable	poor outcome (n = 22)	good outcome (n = 10)	p value	adjusted OR	95% CI	p value
Age, mean±SD, years	34.5±12.3	32.2±10.8	0.45	​	​	​
Gender, n (%)	​	​	0.67	​	​	​
Male	12 (54.5)	6 (60.0)	​	​	​	​
Female	10 (45.5)	4 (40.0)	​	​	​	​
Facial stain, n (%)	​	​	0.04*	5.1	0.9–28.4	0.07
Present	17 (77.3)	2 (20.0)	​	​	​	​
Absent	5 (22.7)	8 (80.0)	​	​	​	​
Laterality, n (%)	​	​	0.22	​	​	​
Unilateral	15 (68.2)	9 (90.0)	​	​	​	​
Bilateral	7 (31.8)	1 (10.0)	​	​	​	​
Tumor response, n (%)	​	​	0.008*	10.5	1.8–60.7	0.008*
Regressed/stable	4 (18.2)	8 (80.0)	​	​	​	​
Other	18 (81.8)	2 (20.0)	​	​	​	​
Recurrences, n (%)	​	​	0.01*	7.8	1.1–52.3	0.03*
Yes	9 (40.9)	0 (0.0)	​	​	​	​
No	13 (59.1)	10 (100.0)	​	​	​	​
Exudative RD, n (%)	​	​	0.03*	4.6	0.8–27.2	0.09
Yes	7 (31.8)	0 (0.0)	​	​	​	​
No	15 (68.2)	10 (100.0)	​	​	​	​

RD, retinal detachment; SD, standard deviation; OR, odds ratio; CI, confidence interval.

*Statistically significant at p < 0.05.

Fig. 1.

a A color fundus photograph of the right eye showing a large orange lesion in the infero-temporal quadrant involving the fovea and extending till periphery. b After treatment with plaque brachytherapy, the lesion reduced in size with pre-retinal fibrosis and some pigment deposits temporal to macula. B-scan showing a large hyper-echoic lesion before treatment (c) which reduced in size after treatment (d).

Discussion

DCH is a rare but vision-threatening ocular manifestation of SWS. It typically presents in early life, often progressing silently until complications, such as ERD or secondary glaucoma, arise [3, 4, 14]. This retrospective study evaluated the demographic profile, clinical features, multimodal imaging characteristics, and treatment outcomes of 29 patients with DCH associated with SWS/PPV, providing one of the most comprehensive institutional experiences from a tertiary referral center in India.

Consistent with the literature, our cohort demonstrated slight female predominance and early disease onset, with most patients presenting before the age of 30 years. This finding aligns with previous reports showing that DCH often manifests in childhood, in contrast to CCHs, which are typically diagnosed in adults. Unilateral ocular involvement was predominant (90%), reflecting the segmental and asymmetrical distribution of SWS-related vascular anomalies. Facial port-wine stain, a classical hallmark of SWS, was observed in over three-quarters of our patients, reinforcing its diagnostic relevance even in resource-limited settings where advanced neuroimaging may not always be readily available [12, 20].

Ocular complications were frequent in our cohort, with ERD observed in 16 of 32 eyes (50%). ERD in DCH is a well-recognized and vision-threatening manifestation that often results from choroidal vascular leakage and breakdown of the outer blood-retinal barrier [2, 4]. Persistent or untreated ERD can result in foveal involvement, photoreceptor degeneration, and permanent visual loss. In our study, although ERD was present in half of the eyes at presentation, post-treatment regression of exudation was achieved in six eyes, highlighting the importance of early intervention. When present, subretinal or IRF is typically documented on SS-OCT, which remains a cornerstone in assessing both the anatomical impact and treatment response in these patients [4, 13, 21, 22].

Glaucoma, a well-recognized complication of DCH in SWS/PPV, was documented in 13 of 32 eyes (41%) in our cohort. This finding is consistent with the existing literature, which estimated the prevalence of glaucoma in SWS to be between 30% and 70%. The pathogenesis of glaucoma varies in SWS [23]. Developmental anomalies affecting the anterior chamber angle in neonates and infants contribute to aqueous outflow obstruction. In contrast, older children and adults typically experience elevated episcleral venous pressure secondary to episcleral vascular malformations, which impair aqueous drainage through the conventional trabecular pathway [24]. DCH increases the risk of neovascular glaucoma development secondary to chronic ERD. Regardless of mechanism, IOP elevation in these patients is frequently insidious and progressive, often causing irreversible optic nerve damage before the onset of clinical symptoms. This underscores the importance of routine IOP screening, optic nerve head evaluation, and early imaging in patients with SWS, even those without overt ocular complaints [25].

Multimodal imaging plays a critical role in the diagnosis and characterization of DCH [26]. B-scan USGconfirmed the classic features of DCH, including dome-shaped choroidal thickening with high internal reflectivity [2]. Our imaging data revealed a mean tumor diameter of 8.3 mm and a mean height of 4.16 mm, values comparable to those of prior reports. Interestingly, SRF and IRF were noted in only four eyes on SS-OCT, suggesting that despite widespread choroidal involvement, fluid accumulation may not always be clinically evident and may fluctuate with disease activity or treatment [27].

Therapeutically, our approach was individualized based on the extent of disease, visual symptoms, and the presence of complications. Plaque brachytherapy and trabeculectomy were the most commonly employed interventions, each used in 24% of patients. EBRT, oral medications (e.g., propranolol), and antiglaucoma medications served as adjuncts or alternatives in select cases [4, 16, 19, 22, 28–30]. The tumor responded favorably in approximately half of the treated eyes, with 7 eyes showing regression and the remaining 7 being stable. Notably, exudative detachment regressed in 6 eyes post treatment, underscoring the potential for anatomical recovery when therapy is timely and targeted appropriately. However, recurrence was observed in 6 eyes, emphasizing the chronic, relapsing nature of DCH and the need for long-term follow-up.

Compared with CCHs, such as those described by Shields et al. [12] DCH presents distinct challenges due to its diffuse nature, early onset, and association with systemic disease. While CCH is often treated with photodynamic therapy or laser therapy, DCH requires a more nuanced, multimodal approach, balancing tumor control, vision preservation, and glaucoma or exudation management, with good outcomes [4].

This study is limited by its retrospective design and variable follow-up duration. Furthermore, imaging data availability was inconsistent across all patients, which may have introduced selection bias when evaluating tumor metrics. Our findings suggest comparable clinical presentation, imaging features, and treatment outcomes between SWS and PPV. Nonetheless, the limited case numbers constrain meaningful statistical analysis, underscoring the need for larger, multicenter studies to better delineate potential differences. However, the strength of our study lies in its focused analysis of a relatively large cohort of patients with DCH in the context of SWS using modern imaging and treatment modalities.

Conclusion

DCH in SWS is a complex, vision-threatening condition that requires early diagnosis and individualized, multimodal treatment. Facial port wine staining remains a valuable clinical clue, and imaging techniques, such as SS-OCT, B-scan USG, and ultra-widefield photography, are instrumental for diagnosis and monitoring. Although treatment can achieve tumor control and anatomical improvement in many cases, recurrence and persistent complications remain a challenge that requires long-term surveillance and multidisciplinary approaches.

Statement of Ethics

This study was conducted in accordance with the Declaration of Helsinki. The collection and evaluation of all protected patient health information were performed in a Health Insurance Portability and Accountability Act-compliant manner. This study was approved by the Institutional Review Board at LV Prasad Eye Institute (Ref No. LEC-BHR-R-01-23-1002). Informed and written consent was obtained from all the study patients to participate in the study prior to performing the procedure, including written permission for publication of all photographs and images included herein.

Conflict of Interest Statement

There are no competing financial interests in relation to the work described in this manuscript. Dr. Vishal Raval was a member of the journal’s Editorial Board at the time of submission.

Funding Sources

This work was supported by The Anant Bajaj Retina Institute and Hyderabad Eye Research Foundation, Hyderabad, India. The authors gratefully acknowledge the support of the Sturge-Weber Foundation for providing grant funding for this study.

Author Contributions

D.P. was responsible for reviewing the literature and writing the first manuscript draft. V.R. was responsible for formulating the contents of the review article, collecting, processing and image analysis, and updating reference lists and critical inputs. S.S. and S.K. were responsible for critically reviewing the manuscript.

Funding Statement

This work was supported by The Anant Bajaj Retina Institute and Hyderabad Eye Research Foundation, Hyderabad, India. The authors gratefully acknowledge the support of the Sturge-Weber Foundation for providing grant funding for this study.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.