Half Fluence Photodynamic Therapy in Peripapillary Circumscribed Choroidal Hemangiomas

doi:10.21203/rs.3.rs-256339/v1

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Half Fluence Photodynamic Therapy in Peripapillary Circumscribed Choroidal Hemangiomas

https://doi.org/10.21203/rs.3.rs-256339/v1

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Purpose

To evaluate the safety and efficacy of half fluence photodynamic therapy (PDT) as treatment for symptomatic peripapillary circumscribed choroidal haemangiomas (CCHs).

Methods

In this prospective, interventional case series; 11 patients with symptomatic peripapillary CCHs presenting to a single centre were treated with half fluence PDT using verteporfin 6 mg/m2 with fluence of 25 mJ/cm2 (standard is 50 mJ/cm2) and other standard settings. Patients were evaluated at baseline, four weeks, twelve weeks and twenty-four weeks post-PDT treatment with best corrected visual acuity (BCVA), ultrasonography, spectral domain- optical coherence tomography (SD-OCT), visual evoked potential and angiographic studies.

Results

Eleven patients with peripapillary CCHs received half fluence PDT. The BCVA significantly improved to 0.558 + 0.118 at four weeks post treatment (P=0.014), to 0.494 + 0.114 at twelve weeks (P=0.006) and 0.441 + 0.125 at twenty-four weeks (P=0.007) from baseline levels of 1.017 + 0.075 on log MAR scales. Similar improvement was observed in central macular thickness (CMT) of 78.50 + 13.73 um(P=0.001) at four weeks; 114.70 + 27.73 um(P=0.003) at twelve weeks and 174.60 + 23.13 um(P=0.001) at twenty-four weeks post treatment. A single session of re-treatment was required in 18%(n=2) of patients which also showed complete resolution at last follow-up. No complications were observed without any significant change in retinal nerve fibre layer (RNFL) thickness at six months follow-up(P=0.088).

Conclusions

Half fluence PDT can be an effective and safe treatment option for peripapillary CCHs which results in both anatomical and functional improvements with no observable complications.

Ophthalmology

Circumscribed choroidal haemangiomas

half-fluence photodynamic therapy

central macular thickness

peripapillary

retinal nerve fibre layer thickness

Choroidal haemangioma is an uncommon benign vascular tumour of the choroid that can be diffuse or circumscribed depending on specific clinical characteristics [1]. The circumscribed choroidal haemangioma (CCH) has unilateral presentation, orange-red tumour colour, round, well-circumscribed shape, and location in the posterior fundus [2]. Fluorescein angiography shows hyper fluorescence, rapid early filling; confirmed on optical coherence tomography (OCT) with dome-shaped contour and absence of choriocapillaris compression [3]. CCH can cause significant visual impairment when exudative activity leads to the development of macular oedema and/or serous retinal detachment and, eventually, photoreceptor loss. Treatment of symptomatic or exudative CCH should be considered in order to preserve vision.

CCHs can be treated with laser photocoagulation, cryotherapy, radiotherapy, proton beam radiotherapy, external beam radiotherapy, plaque radiotherapy and transpupillary thermotherapy [4-9]. These treatments are associated with the potential risk of damage to the overlying retina as well as optic nerve. Many authors exhibited safety and efficacy of photodynamic therapy (PDT) using full fluence in treatment of CCHs with Singh et al reporting choroidal atrophy as possible complication in their study [10-11]. Alkin et al reported reduced complication rate and better efficacy in half fluence PDT treated patients of chronic central serous chorio-retinopathy [12]. Wong et al also found similar efficacy in patients of polypoidal choroidal vasculopathy (PCV) treated with half fluence PDT [13]. Since PDT target abnormal vascularised tissue within the choroid making, it a logical and safe option in the management of CCH as described for PCV or CSCR patients even with low or half fluence settings. Moreover, targeting peripapillary haemangiomas with standard full fluence or bolus PDT can lead to inadvertent damage to vascular supply of optic nerve head resulting in optic atrophy.

Therefore, we conducted present study to evaluate the safety and efficacy of half fluence photodynamic therapy in treatment of symptomatic peripapillary circumscribed choroidal haemangiomas (CCHs).

This prospective interventional study was carried out at tertiary care referral eye hospital in North India. Institutional ethical committee clearance was obtained and study adhered to the principles of the Helsinki Declaration. All patients who were aged 18 and above and had symptomatic peripapillary circumscribed haemangiomas reporting between June 2019 to May 2020 were included after obtaining written informed consent. Patients with history of previous treatment in form of laser, anti-VEGF injections or PDT for haemangioma or any other concurrent retinal diseases were excluded. Initial diagnosis was made based on fundoscopy, Spectral domain-optical coherence tomography (SD-OCT), fundus fluorescein angiography (FFA) and/or indocyanine green angiography (ICG). Baseline visual acuity in log MAR was recorded and SD-OCT scans were performed before treatment and repeated at subsequent observation intervals. OCT scanning was performed using spectral domain OCT (Carl Zeiss Meditec, Inc., 5160 Hacienda Drive, Dublin, CA 94568 USA), with both radial and line OCT scanning of macula as well as optic disc cube scans were obtained. The baseline visually evoked potential (VEP)evaluation before treatment and at six-month follow-up was carried out in all patients. The typical fundus appearance, ultrasonographic features, SD-OCT images and baseline retinal nerve fibre layer thickness maps (case 2) are shown in Fig 1. After informed consent, half-fluence PDT was performed. A standard dose of 6 mg/m2 intravenous Visudyne (Verteporfin) was used and infused over 10min. The laser power (Quantel PDT laser) was set at half fluence of 25 mJ/cm2 (standard is 50 mJ/cm2) and was applied over 83s. The laser was applied 15min after the commencement of infusion using a ×1.6 magnification contact lens (Volk® PDT lens; Volk Optical Inc., Mentor, OH, USA) as a single spot. The laser spot size varied in each patient, related to the size of the treated area. Laser spot was adjusted to cover lesion area with distance of 200um from disc margin as safety measure in each patient. At follow up visits, BCVA assessment, SD-OCT imaging for measurement of central macular thickness (CMT) as well as retinal nerve fibre layer (RNFL) thickness and VEP recordings were repeated. Patients were evaluated at 04 weeks, 12 weeks and 24 weeks. In cases of sub-foveal fluid persistence or recurrence at 03 months, repeat half fluence PDT was performed with same laser settings as initial treatment.

Statistical Analysis

Standard weighted one-way analysis of variances (ANOVA) was performed to identify any relationship between the change in log MAR visual acuity and central macular thickness from pre-treatment and follow-up visits at 04 week, 12 weeks and 24 weeks. Paired T-test was used to compare effect of half fluence PDT on pre and post-treatment RNFL thickness. The p-value of > 0.05 was considered statistically significant.

Of the total of 13 patients with symptomatic peripapillary circumscribed haemangiomas, who were subjected to half fluence PDT during study period only 11 completed the required follow-up of six months post intervention. The average age of patients was 54.72 + 9.96 years(n=11) with male preponderance (n=7; 63%). All patients were symptomatic with diminution of vision and had macular serous detachment. The demographic and clinical features of patients are included in Table 1. The structural as well as functional improvement was seen in all patients (n=11; 100%) as well as on imaging evaluation as shown in case 2 [Fig 2].

The average BCVA in pre-treatment group was 1.017 + 0.075 which significantly improved to 0.558 + 0.118 at four weeks post treatment(P=0.014). The BCVA further improved to 0.494 + 0.114 at twelve weeks (P=0.006) and 0.441 + 0.125 at twenty-four weeks post treatment(P=0.007) from baseline levels [Fig 3]. The change in BCVA was not statistically significant in comparison between 04 weeks and 12 weeks(P=0.058).

All patients(n=11;100%) were visually symptomatic with presence of serous macular detachment and mean CMT at baseline was 564.60 + 18.485um. Patients showed statistically significant reduction in CMT at four weeks of 78.50 + 13.73 um(P=0.001); 114.70 + 27.73 um(P=0.003) at twelve weeks and 174.60 + 23.13 um(P=0.001) at twenty-four weeks post treatment from baseline [Fig 4]. Two patients(n=2;18%) had minimal reduction in subretinal fluid which required repeat single session of half fluence PDT at 12 weeks post initial treatment with complete resorption of subretinal fluid. The change in CMT was not statistically significant when compared between 04 weeks and 12 weeks(P=0.088).

No adverse events or complications of treatment were noted in any patient. The baseline average RNFL thickness before treatment was 120.68 + 5.372 um. At twenty-four weeks post treatment, average RNFL thickness was 116.86+ 4.38(P=0.62) which was not statistically significant from pre-treatment levels [Fig5]. The comparison of VEP measurements pre- and post-PDT treatment did not show increase in P100 latency or decrease in amplitude in any patient.

PDT is considered to be the treatment of choice for choroidal haemangioma, as it selectively targets abnormal choroidal vessels without damaging the overlying neurosensory retina. It is indicated in symptomatic patients resulting due to macular oedema or subretinal fluid [14]. The various protocols for PDT described for the treatment of choroidal haemangioma are; ‘standard’, ‘bolus’ and ‘high fluence’ protocols; which use standard dose of verteporfin but vary in additional settings [15-18]. The tumour control; usually defined as the elimination of exudation rather than complete tumor shrinkage can be achieved in the vast majority of the patients with every protocol. But, there is significant potential for choroidal atrophy and other adverse events following PDT as observed by multiple researchers [10, 19] with varying rate of success with single session of treatment. The optic disc vasculature can also be at risk of potential ischemia; especially in peripapillary choroidal haemangiomas.

The present study; is first attempt at evaluating efficacy and safety of half fluence PDT for symptomatic CCHs. It showed that half-fluence PDT can have a significant effect on improvement of a patient’s visual acuity, in resolving SRF and reducing central retinal thickness. Tumour control was observed in all patients with significant improvement in BCVA at all observation points and last follow-up at six-months. The significant visual improvement in present study were similar to earlier studies where standard, bolus or high fluence protocols were used [19-22]. Many of these studies required multiple session of PDT treatment but additional session of half fluence PDT in our study was required in only two cases (18%). Similarly, successful anatomical outcomes in form of resolution of macular oedema or subretinal fluid with single session treatment was observed in nine patients (82%) at twelve weeks follow-up and complete resolution at six-month follow-up in all patients with additional session of half fluence PDT. Similar positive results were also seen with half fluence PDT in other choroidal pathologies like central serous chorioretinopathy and polypoidal choroidal vasculopathy which also predominantly affect choroidal vascular permeability [12,13].

Vision threatening complications in form of choroidal atrophy, choroidal effusion and perifoveal haemorrhage has been reported with standard PDT protocols [10,19,23]. None of these complications were seen in present study. Moreover, effect of half fluence PDT was further assessed with comparison of pre and post-treatment RNFL thickness and visually evoked potential (VEP). No adverse effect of half fluence PDT on RNFL thickness as well as VEP values was observed in our study. This probably resulted from lesser energy delivered per unit area due to half fluence PDT protocol as well as single laser spot used with a safety margin of 200um from optic disc margins. Bernstein et al also reported successful resolution of peripapillary choroidal neovascular membrane with PDT treatment which included application over optic disc also without any clinical evidence of optic nerve damage. However, objective assessment of optic nerve damage with OCT imaging study was not performed [24].

Our study is not without its limitations, as it has small number of patients and lacks a control group. The strengths of our study are that it includes long-term follow up of a cohort of patients who received half- fluence PDT. Patients were followed up for a considerable long period following treatment without any observable long term ill effects. Moreover, a new variable in form of change in RNFL thickness was studied to validate safety of half fluence protocol of PDT treatment.

In summary, our study provides considerable information that half fluence PDT can be used to successfully treat symptomatic circumscribed choroidal haemangiomas (CCHs) without any observable complications. However, we recognise that a large, prospective, comparative study would provide more significant evidence as to whether present protocol is safe and effective treatment modality.

Acknowledgements: - Nil

Conflict of interest: - The Authors declare that there is no conflict of interest.

Funding: - The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethics approval: - Obtained from institutional ethical committee

Patient’s Consent: - Obtained from patient for participation as well as publication of manuscript.

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Table 1: Demographic and clinical features of patients with juxta-papillary circumscribed choroidal haemangiomas (CCHs)

Case	Age	Sex	Pre-treatment BCVA (log MAR)	Pre-treatment CMT (um)	Retreatment required or not	Any Adverse events or complications

1	63	F	1	563	No	Nil
2	55	M	1	568	No	Nil
3	41	M	0.8	559	Yes; Half fluence PDT repeated	Nil
4	56	M	1.3	704	No	Nil
5	54	M	1	510	No	Nil
6	62	F	1.3	542	No	Nil
7	65	M	1.07	524	No	Nil
8	59	F	0.6	503	No	Nil
9	37	M	0.8	611	No	Nil
9	66	F	1.3	553	Yes; Half fluence PDT repeated	Nil
10	44	M	1	572	No	Nil
11	63	F	1	563	No	Nil

BCVA, best corrected visual acuity; log MAR, logarithm of minimum angle of resolution; CMT, central macular thickness; PDT, photodynamic therapy

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Reviews received at journal
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Reviewers invited by journal
26 Feb, 2021
Editor assigned by journal
21 Feb, 2021
First submitted to journal
18 Feb, 2021

You are reading this latest preprint version

Half Fluence Photodynamic Therapy in Peripapillary Circumscribed Choroidal Hemangiomas

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