Half Fluence Photodynamic Therapy in Peripapillary Circumscribed Choroidal Hemangiomas

Purpose To evaluate the safety and ecacy of half uence 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 uence PDT using verteporn 6 mg/m2 with uence 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.


Introduction
Choroidal haemangioma is an uncommon benign vascular tumour of the choroid that can be diffuse or circumscribed depending on speci c 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 uorescence, rapid early lling; con rmed on optical coherence tomography (OCT) with dome-shaped contour and absence of choriocapillaris compression [3]. CCH can cause signi cant 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.
Many authors exhibited safety and e cacy of photodynamic therapy (PDT) using full uence 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 e cacy in half uence PDT treated patients of chronic central serous chorio-retinopathy [12]. Wong et al also found similar e cacy in patients of polypoidal choroidal vasculopathy (PCV) treated with half uence 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 uence settings. Moreover, targeting peripapillary haemangiomas with standard full uence 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 e cacy of half uence photodynamic therapy in treatment of symptomatic peripapillary circumscribed choroidal haemangiomas (CCHs).

Materials And Methods
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 uorescein 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 bre layer thickness maps (case 2) are shown in Fig 1. After informed consent, half-uence PDT was performed. A standard dose of 6 mg/m2 intravenous Visudyne (Vertepor n) was used and infused over 10min. The laser power (Quantel PDT laser) was set at half uence 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 magni cation 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 bre layer (RNFL) thickness and VEP recordings were repeated. Patients were evaluated at 04 weeks, 12 weeks and 24 weeks. In cases of sub-foveal uid persistence or recurrence at 03 months, repeat half uence 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 uence PDT on pre and post-treatment RNFL thickness. The p-value of > 0.05 was considered statistically signi cant.

Results
Of the total of 13 patients with symptomatic peripapillary circumscribed haemangiomas, who were subjected to half uence 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].

Discussion
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 uid [14]. The various protocols for PDT described for the treatment of choroidal haemangioma are; 'standard', 'bolus' and 'high uence' protocols; which use standard dose of vertepor n but vary in additional settings [15][16][17][18]. The tumour control; usually de ned 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 signi cant 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 rst attempt at evaluating e cacy and safety of half uence PDT for symptomatic CCHs. It showed that half-uence PDT can have a signi cant 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 signi cant improvement in BCVA at all observation points and last follow-up at six-months. The signi cant visual improvement in present study were similar to earlier studies where standard, bolus or high uence protocols were used [19][20][21][22]. Many of these studies required multiple session of PDT treatment but additional session of half uence PDT in our study was required in only two cases (18%). Similarly, successful anatomical outcomes in form of resolution of macular oedema or subretinal uid 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 uence PDT. Similar positive results were also seen with half uence 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 uence PDT was further assessed with comparison of pre and post-treatment RNFL thickness and visually evoked potential (VEP). No adverse effect of half uence 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 uence 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 halfuence 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 uence protocol of PDT treatment.
In summary, our study provides considerable information that half uence 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 signi cant evidence as to whether present protocol is safe and effective treatment modality.