Half-fluence photodynamic therapy to treat chronic central serous chorioretinopathy: A case series.

OBJECTIVE: To evaluate the efficacy and safety of half-fluence photodynamic therapy (PDT) in treating chronic central serous chorioretinopathy (CSC) in Omani population.
MATERIALS AND METHODS: A Retrospective chart review of all patients with chronic CSC treated with half-fluence PDT from November 2009 to December 2010 was carried out. Recorded parameters included best-corrected visual acuity, findings of clinical examination, results of fluorescein angiography and optical coherence tomography at baseline and during follow-up visits after treatment.
RESULTS: Six eyes (of five Omani patients) with chronic CSC, of at least 9 months duration, were treated with half-fluence PDT. All eyes showed a complete resolution of CSC within 1 month following treatment. Four eyes showed visual improvement and two had unchanged stable vision. No complications from the treatment were noticed during the follow-up visits.
CONCLUSION: Half-fluence PDT to treat chronic CSC in Omani population is a promising treatment that results in both structural and functional improvement.

Introduction

Central serous chorioretinopathy (CSC), which is also known as Central Serous Retinopathy (CSR), is an acquired macular disease typically affecting young males. Males account for 72–88% of the affected population.[1] It is bilateral in up to 40% of cases.[1] The most common symptoms are reduced vision and micropsia. Fundus examination shows one of three presentations: neurosensory detachment, pigment epithelium detachment (PED), or mixed type. The pathogenesis of CSC is still not completely understood. One theory suggests that fluid from choroid escapes into subretinal space through a defect in tight junctions between the retinal pigment epithelium (RPE) cells.[2] Another suggests that RPE cells lose their normal polarity and pump fluid from the choroid toward the retina, causing a neurosensory detachment.[2] Studying the abnormalities of choroidal circulation in CSC by indocyanine green (ICG) has led to new theories regarding pathogenesis of CSC. In many patients, ICG reveals multifocal areas of choroidal vascular hyperpermeability which may lead to mechanical disruption of the RPE barrier with subsequent subretinal fluid accumulation.[2] Metabolic stress on the RPE was observed in cases of CSC.[3] Risk factors for CSC are: personality type-A, steroid use, pregnancy, alcohol use, antibiotic use, antihistamine use, autoimmune diseases, tobacco use, and untreated hypertension.[4]

Observation is usually the initial step in treating patients with acute CSC. The followings are indications to treat CSC: persistent or chronic CSC (>3-4 months), recurrences in eyes with visual deficits from CSC, visual deficits in the fellow eye from CSC, presence of chronic changes like cysts, and occupational reasons.[5] Treatment options include laser photocoagulation (argon or micropulse diode lasers) and/or photodynamic therapy (PDT).[6-15]

PDT has some advantages over laser photocoagulation in treating CSC. Permanent scotomas and scar formation with permanent foveal damage are known adverse effects from macular photocoagulation.[716] On the other hand, PDT does not have clinically visible structural damage and it usually will not result in persistent scotomas. However, some studies showed that standard dose PDT might be associated with choriocapillaris hypoperfusion that may result in decreased vision.[1517] The standard regime for using PDT is to give a patient intravenous verteporfin at a dose of 6 mg/m2 over 10 minutes. Then, 5 minutes later, diode laser at a wavelength of 689 nm and energy of 50 mJ/cm2 over 83 seconds is directed to the target lesion of the eye. The laser spot size is adjustable according to the lesion size. In this case series, we report the efficacy and safety of half-fluence PDT in the treatment of five Omani patients (six eyes) with chronic CSC. The dose of verteporfin used is similar to what is recommended by FDA, but laser energy of 25 mJ/cm2 (half fluence) over 83 seconds was applied to the lesion.

Materials and Methods

All patients with chronic CSC who presented to the Department of Ophthalmology at the Sultan Qaboos University Hospital (SQUH) between November 2009 and December 2010 were included in the study. All patients had been evaluated by one retina specialist (AA). Diagnosis of CSC was based on clinical findings and ancillary tests such as fundus fluorescein angiography (FFA) and optical coherence tomography (OCT). Distance visual acuity was assessed with the Early Treatment Diabetic Retinopathy (ETDRS) chart. Macular OCT and FFA were performed in all patients prior to the treatment. Treatment with PDT was initiated once a complete ophthalmic assessment was done. ICG study was not performed because of unavailability. The spot size of treatment was measured by using the fluorescein images. The delivered laser energy, which was used during treatment sessions, was half of the standard dose (half-fluence PDT), i.e. 25 mj/cm2 over 83 seconds. Intravenous verteporfin was given at a dose of 6 mg/m2 over 10 minutes as recommended by FDA. All patients were admitted to the hospital for the treatment and instructed to avoid sun exposure for 3 days post-treatment. Chart review of electronic medical records for these patients was done to collect appropriate data. Follow-up visits were at months 1, 3, 6 and 12 post-treatment. OCT was done for all patients in all follow-up visits. FFA was not done post-treatment for all patients, since they all showed improvement clinically and by OCT in all visits.

Results

The demographic details, duration of CSC and follow-up periods for the study patients are given in Table 1. All patients were of Omani origin. There were three males and two females. The average age was 41 years (range 34-50 years). Three patients (two males and one female) had bilateral chronic CSC and the two other patients had unilateral chronic CSC. All patients had been referred from other institutions for management. No prior therapy had been instituted.

Table 1

Demographic features of patients

All patients had CSC for at least 9 months. Five eyes (out of eight) had a neurosensory detachment type of CSC, two had PED, and one had a mixed type of CSC. The average duration of CSC in all patients was 3 years (range 9 month to 10 years). All patients had undergone FFA and OCT prior to the treatment [Figure 1].

Figure 1

Early and late phase of FFA for left eye of patient no. 1 shows leaking hyperfluorescence in ink-dot, expansile pattern

Two patients (no. 1 and 2) with bilateral CSC received PDT only in one eye because the visual acuity in the non-treated eye was 6/6. The average period of follow-up for all patients was 7 months (range 2-12 months). Table 2 summarizes the five patients with pre- and post-PDT macular status and best-corrected visual acuity (BCVA) [Figures 2 and 3].

Table 2

Pre- and post-PDT macular status and BCVA in all patients

Figure 2

Fundus fluorescein angiography and optical coherence tomography of both eyes of patient no. 5 pre-photodynamic therapy. Upper images row (a, b, c) for right eye shows early and late phases of fundus fluorescein angiography and optical coherence tomography. Lower images row (d, e, f) for left eye shows early and late phases of fundus fluorescein angiography and optical coherence tomography

Figure 3

Optical coherence tomography of both eyes of patient no. 5 post-photodynamic therapy: (a) right eye; (b) left eye

Of eight eyes with chronic CSC, six were treated with the half-fluence PDT. All treated eyes showed a complete resolution of the CSC within 1 month of therapy. Persistent neurosensory CSC was seen in one of the untreated eyes, but with 6/6 visual acuity (left eye of patient no. 1). On the other hand, an untreated eye with PED-type CSC had a complete resolution of the PED after the fellow eye was treated (left eye of patient no. 2).

Of the six treated eyes, visual acuity improved in four eyes and remained unchanged in two eyes. There was no deterioration of visual acuity after PDT in any eye. The improvement of visual acuity (VA) in the four eyes was more than double (from pre-PDT VA average logMAR 0.40 to post-PDT VA average logMAR 0.15). For all six treated eyes, mean improvement in acuity was from logMAR value of 0.38 to 0.19. During the follow-up period, no recurrence of CSC was observed in any eye. In addition, there was no deterioration of visual acuity or other adverse effects.

Discussion

CSC is a common acquired maculopathy. Acute CSC usually resolves spontaneously with very good visual acuity.[18] However, chronic CSC may need treatment since vision can be permanently affected.[19] Laser photocoagulation was used for decades before the era of PDT. However, laser photocoagulation may not accelerate resolution and does not reduce the recurrence rate.[6] In addition, it may result in permanent visual defects.[7]

In our case series in Omani patients, results showed that middle-aged males are more affected than females with CSC and bilateral disease is more common than unilateral. These conclusions are similar to what has been found in previous studies.[14] All treated eyes responded well within 1 month after a single session of half-fluence PDT. A previous study in Omani patients with CSC showed complete resolution of unilateral CSC with a single session of PDT.[20] The dose of delivered energy was not mentioned in that study.

Of the six treated eyes, four showed improvement in visual acuity after therapy. The remaining two eyes with unchanged acuity were right eye of patient no. 4 and right eye of patient no. 5. The first had neurosensory detachment type of CSC for around 10 years. The prolonged period of such CSC might result in permanent damage to photoreceptors, and hence, permanent visual loss. The second eye had a mixed-type of CSC for around 2 years. The longstanding CSC could also be the reason of non-improvement in vision of that eye. We can conclude that long duration of CSC is a risk factor for permanent visual loss.

Verteporfin was approved by FDA in 2000 to treat wet age-related macular degeneration by light sensitization (PDT). It started to be used in the treatment of CSC soon after that.[11] The mechanism of action in treating CSC is not fully clear. However, it is believed that short-term hypoperfusion of choriocapillaris occurs followed by remodeling of choroidal vessels.[38-1018]

Multiple studies showed that PDT is a useful treatment for acute and chronic CSC.[891115] Most of these studies were performed with the use of standard-fluence PDT, in which 50 mJ/cm2 of energy was used. However, half-fluence PDT (25 mJ/cm2 ) was only investigated in two studies, in which a comparison between standard fluence and half fluence was made.[1421] These studies concluded that there was no difference of visual acuity and subretinal fluid reabsorption between both regimes. However, atrophic changes and choroidal neovascularization developed in two patients treated with standard-fluence PDT.[14] In addition, there was a significant reduction of choriocapillaris perfusion in the standard-fluence PDT group.[21] In our study, all treated eyes received half-fluence PDT and no adverse effects were observed. However, one eye (left eye of patient no. 2) with PED-type CSC of 1-year duration showed a complete resolution although treatment targeted the fellow eye. Spontaneous resolution of CSC of that eye is not understood.

Patients with CSC usually have good visual prognosis with a favorable natural course. However, few need treatment. PDT is currently used to treat CSC with promising results for both acute and chronic types. A non-comparative study carried out for acute CSC, in which half-dose verteporfin with standard-fluence PDT was used, showed a successful outcome.[13] Recent studies have also investigated the role of anti-vascular endothelial growth factors (bevacizumab) as a treatment for this disorder, with promising results in terms of visual acuity and anatomical restoration, although the sample size was small (six patients).[22] Another study showed shortening of resolution time of CSC by using acetazolamide.[23] Half-fluence PDT, rather than full dose of delivered energy, should be studied in a larger sample size to draw strong conclusions about this modality of treatment for chronic CSC.