Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

Long-Term Efficacy and Safety of Photodynamic Therapy in Patients With Chronic Central Serous Chorioretinopathy

Young Joo Park, MD; Yong-Kyu Kim, MD; Kyu Hyung Park, MD, PhD; Se Joon Woo, MD, PhD

Abstract

BACKGROUND AND OBJECTIVE:

To investigate the long-term results of photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSCR).

PATIENTS AND METHODS:

The authors reviewed patients with chronic CSCR treated with verteporfin PDT in their hospital and followed up for 36 months or longer.

RESULTS:

Among 94 eyes, 76 eyes underwent half-fluence PDT (80.9%), 12 eyes (12.8%) underwent half-dose PDT, and six eyes (6.4%) underwent standard PDT. Mean follow-up duration was 58.1 months± 20.3 months. Mean best-corrected visual acuity improved by 0.15 ± 0.31 logMAR. Seventy-two eyes (77%) had resolution of subretinal fluid 1 month after treatment. Nine eyes (9.6%) showed nonresponse, and 23 (24.5%) showed recurrence. Older age (P = .009) and smaller macular thickness reduction post-PDT (P = .017) were associated with nonresponse. Male sex (P = .021), bilateral CSCR (P = .008), and smaller choroidal thickness reduction (P = .024) were associated with recurrence. Retreatment using PDT resulted in a 90% success rate.

CONCLUSIONS:

Verteporfin PDT for chronic CSCR conferred good visual outcomes, as well as good safety results up to mean 5 years. Although the disease recurred in about one-fifth of the eyes, additional PDT conferred a good response rate.

[Ophthalmic Surg Lasers Imaging Retina. 2019;50:760–770.]

Abstract

BACKGROUND AND OBJECTIVE:

To investigate the long-term results of photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSCR).

PATIENTS AND METHODS:

The authors reviewed patients with chronic CSCR treated with verteporfin PDT in their hospital and followed up for 36 months or longer.

RESULTS:

Among 94 eyes, 76 eyes underwent half-fluence PDT (80.9%), 12 eyes (12.8%) underwent half-dose PDT, and six eyes (6.4%) underwent standard PDT. Mean follow-up duration was 58.1 months± 20.3 months. Mean best-corrected visual acuity improved by 0.15 ± 0.31 logMAR. Seventy-two eyes (77%) had resolution of subretinal fluid 1 month after treatment. Nine eyes (9.6%) showed nonresponse, and 23 (24.5%) showed recurrence. Older age (P = .009) and smaller macular thickness reduction post-PDT (P = .017) were associated with nonresponse. Male sex (P = .021), bilateral CSCR (P = .008), and smaller choroidal thickness reduction (P = .024) were associated with recurrence. Retreatment using PDT resulted in a 90% success rate.

CONCLUSIONS:

Verteporfin PDT for chronic CSCR conferred good visual outcomes, as well as good safety results up to mean 5 years. Although the disease recurred in about one-fifth of the eyes, additional PDT conferred a good response rate.

[Ophthalmic Surg Lasers Imaging Retina. 2019;50:760–770.]

Introduction

In central serous chorioretinopathy (CSCR), serous pigment epithelial detachment occurs, causing subretinal fluid (SRF) and choroidal fluid leakage. Photodynamic therapy (PDT) has been shown to have effects on CSCR by sealing vascular leakage by altering the chorioretinal vascular structures using the photosensitizing intravenous drug verteporfin (Visudyne; Bausch + Lomb, Rochester, NY) in combination with a low-power, long-duration, infrared laser.1 It has demonstrated more favorable outcomes with less recurrence than anti-vascular endothelial growth factor (VEGF) treatment in the treatment of CSCR.2,3

Since early 2010, several studies have reported half-dose (PDT with full-fluence [50 J/cm2] and a reduced verteporfin dose [3 mg/m2]) and half-fluence PDT (PDT with reduced laser fluence [25 J/cm2] and a full verteporfin dose [6 mg/m2]) in the treatment of CSCR, demonstrating that those sufficiently resolves SRF leakage while decreasing hypoxic damage and consequent complications.4–6 Both half-fluence and half-dose PDT have a similar efficacy to conventional PDT, with fewer harmful side effects.3,7,8 9,10 In a long-term, observational study for half-dose PDT (3-year follow-up; 79 eyes of 73 patients), the proportion of recurrence or incomplete resolution of SRF leakage was 19%.11

Evidence from long-term follow-up is still lacking regarding which factors determine treatment success. The present study aimed to provide evidence for the efficacy of PDT in the treatment of CSCR. The investigation focused on long-term visual prognosis, safety data, and survival analysis of recurrence in patients who were followed up for more than 3 years. Additionally, we investigated which factors contribute to nonresponse and recurrence by regression analysis.

Patients and Methods

Patient Selection

The institutional review board (IRB) of Seoul National University Bundang Hospital approved this retrospective study (IRB No. B-1804/463-101), which adhered to the tenets of the Declaration of Helsinki.

The present study included 94 eyes from 88 patients with chronic CSCR who (1) had undergone verteporfin PDT in Seoul National University Bundang Hospital between March 2003 and February 2015, and (2) had visited the same clinic for at least 3 years from the day of treatment. CSCR was diagnosed when fluorescein angiography (FA) showed the characteristic, well-circumscribed, round SRF accumulation with active leakage sites in the fovea. The CSCR was regarded as chronic when symptoms persisted for more than 6 months, or when widespread pigment epithelial changes were observed using optical coherence tomography (OCT).

We excluded patients with other chorioretinal disorders, such as choroidal neovascularization or polypoidal choroidal vasculopathy by indocyanine green angiography (ICGA) (Heidelberg Retina Angiography, Heidelberg Engineering, Heidelberg, Germany), those treated using anti-VEGF injection before the initial PDT, those who had previously received PDT, or those with a history of any intraocular surgery other than cataract surgery.

Procedure of Photodynamic Therapy

We performed PDT in patients with chronic CSCR who had provided informed consent. Only the patients with subfoveal fluid were treated. Most patients underwent half-fluence PDT with reduced laser fluence (25 J/cm2, 689-nm laser, 83-second treatment time) and a full verteporfin dose (6 mg/m2 Visudyne; Novartis AG, Basel, Switzerland). Half-dose PDT with full fluence (50 J/cm2) and a reduced verteporfin dose (3 mg/m2), or standard PDT with full fluence (50 J/cm2) and a full verteporfin dose (6 mg/m2) were also performed at investigator's discretion. The PDT spot size was defined as the diameter of the smallest circle covering the main hyperpermeable choroidal lesion that resulted in SRF accumulation, as identified on mid-phase ICGA. If there were two distinct choroidal hyperpermeable lesions, both were measured and treated separately during the same PDT session.

Treatment Response and Recurrence

An “initial response” was defined as the SRF disappearance within 6 months after the first PDT. Patients with SRF persisting for 6 months or longer were deemed nonresponsive. “Recurrence” was identified when subfoveal SRF re-appeared after the initial response, as visualized by OCT. The first recommendation in such cases was secondary PDT, with the same fluence and verteporfin dose that was used at the first PDT. However, in the two cases of recurrence and one case of nonresponse (all three cases were treated with half-fluence PDT as the first-line treatment), we used standard-fluence PDT as the second-line treatment after discussion with the patients. If the patient declined re-treatment with PDT, intravitreal anti-VEGF injection was performed. Only when the patient requested, PDT combined with intravitreal anti-VEGF injection was performed.

Data Collection

We collected the patients' medical history, including symptom onset, history of corticosteroid administration, and diagnosis of diabetes mellitus or hypertension. Before treatment, we performed best-corrected visual acuity (BCVA), slit-lamp examination, funduscopy, and imaging studies, which included fundus photography (VX-10; Kowa OptiMed, Tokyo, Japan), FA, ICGA, and spectral-domain OCT (SD-OCT) (Spectralis OCT; Heidelberg Engineering, Heidelberg, Germany). At every following visit, we performed a BCVA test, slit-lamp examination, funduscopy, and OCT.

Outcome Measurement

BCVA measurements were converted to the logarithm of the minimal angle of resolution (logMAR). Central subfield macular thickness (CSMT) was defined as the average thickness of the central 1-mm diameter circle (C1) of the Early Treatment of Diabetic Retinopathy Study grid. Subfoveal choroidal thickness (SFCT) was defined as a distance between the outer portion of the retinal pigment epithelium (RPE)-Bruch's membrane and the inner surface of the sclera, as in a previous study.10 The average of two measurements from the horizontal and vertical scans was recorded. Reduction in CSMT in the first month was defined using the following calculation: (reduction in CSMT 1 month after treatment)/(pre-treatment CSMT). Reduction in SFCT in the first month was defined as follows: (reduction of SFCT 1 month after treatment)/(pre-treatment SFCT).

Any macular structural change that appeared after PDT was documented, including RPE disruption, pigment epithelial detachment (PED), and choroidal neovascularization (CNV), including polypoidal choroidal vasculopathy. The RPE was considered disrupted if there was hypertransmission of the OCT signal below Bruch's membrane.12 Complete photoreceptor recovery was determined when there was a continuous ellipsoid zone (EZ) and a discernible interdigitation zone (IZ) on the SD-OCT images, as in a previous study.13

Statistical Analysis

We analyzed demographics and temporal changes in clinical data. Continuous variables are expressed as mean ± standard deviation. Univariate analyses were performed using Pearson's Chi-square test and Fisher's exact test for categorical variables, and the independent t-test for continuous variables. Predictive factors with a P value of less than .10 in the univariate analyses were simultaneously entered into a backwards stepwise model selection process for Cox proportional hazard analysis and binary logistic regression analysis. The selection process continued until the only remaining predictive factors in the model had a P value of less than .01. Cox proportional hazard analysis could not be carried out in the non-response group. All P values less than .05 were considered statistically significant.

Results

A total of 94 eyes of 87 patients were included in the current study. The demographics and treatment variables are presented in Table 1. The mean follow-up duration was 58.1 months ± 20.3 months (range: 36.1 to 142.6 months) after the initial PDT, and the mean age at the initial PDT was 47.9 years ± 7.1 years (range: 32.6 to 76.6 years). Three patients (four eyes) had history of corticosteroid usage and all were responsive to PDT treatment. Among them, two patients who had oral corticosteroid and one patient with history of intra-articular corticosteroid injection stopped the administration of corticosteroid after the diagnosis of CSC. The initial mean BCVA was 0.34 ± 0.33 logMAR, which corresponds to a Snellen equivalent of 20/44. Half-fluence PDT with a standard verteporfin dose was carried out in 76 eyes (81%); 12 eyes (13%) underwent half-dose PDT, and six (6%) underwent standard PDT.

Demographics, Pre-Treatment Clinical Features, and Treatment Variables of Subjects

Table 1:

Demographics, Pre-Treatment Clinical Features, and Treatment Variables of Subjects

Temporal changes in BCVA, CSMT, SFCT, and presence of SRF leakage after the initial PDT were listed as the treatment outcomes in Table 2. All the listed variables showed significant decreases compared with the pre-treatment data. The mean BCVA at the last visit was 0.19 ± 0.36 logMAR (Snellen equivalent: 20/31). Visual acuity improvement throughout the entire follow-up period was 0.15 ± 0.31 logMAR (ETDRS equivalent: 7.5 letters). The proportion of eyes with persistent and recurrent SRF leakage and with CSMT tended to decrease sharply during the first month and then to maintain throughout the follow-up period (Figure 1). Meanwhile, the BCVA of the treated eyes gradually improved throughout the initial 12 months, showing only minor changes subsequently until the final visit. Among the 91 eyes in which pre-treatment OCT showed a defect in the IZ, EZ, and RPE-Bruch's membrane, 29 (32%) showed complete recovery of the photoreceptor layer defect at the final visit. The mean elapsed time to complete photoreceptor recovery was 34.4 months ± 19.4 months. Two eyes showed newly appeared choroidal neovascularization. Otherwise, no adverse events were observed.

Treatment Outcomes Before and After the Initial PDT in Chronic Central Serous Retinopathy

Table 2:

Treatment Outcomes Before and After the Initial PDT in Chronic Central Serous Retinopathy

Long-term changes in ophthalmic parameters after the initial photodynamic therapy (PDT) for chronic central serous chorioretinopathy. (A) Changes in best-corrected visual acuity (BCVA) (logMAR). (B) Changes in central subfield macular thickness (CSMT) (μm) and proportion of eyes with subretinal fluid (SRF) (%). (C) Changes in subfoveal choroidal thickness (SFCT). Error bars represents standard error means. Asterisks (*) above the error bars indicate statistical significance in comparison with baseline parameters.

Figure 1.

Long-term changes in ophthalmic parameters after the initial photodynamic therapy (PDT) for chronic central serous chorioretinopathy. (A) Changes in best-corrected visual acuity (BCVA) (logMAR). (B) Changes in central subfield macular thickness (CSMT) (μm) and proportion of eyes with subretinal fluid (SRF) (%). (C) Changes in subfoveal choroidal thickness (SFCT). Error bars represents standard error means. Asterisks (*) above the error bars indicate statistical significance in comparison with baseline parameters.

Nine eyes (10%) in which SRF leakage persisted beyond 6 months after the initial PDT were classified as the non-response group, including partial reduction of SRF (Figure 2). Among the 85 eyes in which SRF leakage subsided within 6 months of the initial PDT, 23 (24%) showed recurrence of SRF leakage. The time span from initial PDT to recurrence was 28.6 months ± 20.8 months (range: 1.1 to 86.3 months). Kaplan-Meyer survival analysis showed a cumulative probability of recurrence of 0.297 at 57.8 months (Figure 3). Table 3 shows the univariate and multivariate analyses of the clinical factors associated with non-response. Older age (odds ratio [OR] = 1.215; P = .009) and smaller reduction in CSMT over the first month (OR = 0.939; P = .017) were associated with non-response in the stepwise multiple logistic regression analysis. Regression analyses for recurrence were conducted in the same manner (Table 4) and found that male sex (OR = 20.417; P = .007), bilateral CSCR (OR = 3.407; P = .048), and smaller reduction in choroidal thickness (OR = 0.936; P = .028) showed significant association with recurrence. In the Cox proportional hazard model, male sex (hazard ratio [HR] = 10.781; P = .021), bilateral CSCR (HR = 3.315; P = .008), and smaller reduction in choroidal thickness (HR = 0.951; P = .024) were associated with recurrence.

Schematic image showing the treatment flow according to response to initial photodynamic therapy (PDT). Response was defined as complete resolution of subretinal fluid (SRF) in 6 months after the treatment. Nonresponse group was defined as the eyes with SRF persisting for longer than 6 months after the first PDT. VEGF = vascular endothelial growth factor.

Figure 2.

Schematic image showing the treatment flow according to response to initial photodynamic therapy (PDT). Response was defined as complete resolution of subretinal fluid (SRF) in 6 months after the treatment. Nonresponse group was defined as the eyes with SRF persisting for longer than 6 months after the first PDT. VEGF = vascular endothelial growth factor.

Kaplan-Meyer survival curve for cumulative rate of recurrence after photodynamic therapy (PDT) for chronic central serous chorioretinopathy.

Figure 3.

Kaplan-Meyer survival curve for cumulative rate of recurrence after photodynamic therapy (PDT) for chronic central serous chorioretinopathy.

Risk Factors for Non-Response Until 6 Months After the Photodynamic Therapy for Chronic Central Serous Retinopathy*

Table 3:

Risk Factors for Non-Response Until 6 Months After the Photodynamic Therapy for Chronic Central Serous Retinopathy

Risk Factors for Recurrence After Photodynamic Therapy for Chronic Central Serous Retinopathy*

Table 4:

Risk Factors for Recurrence After Photodynamic Therapy for Chronic Central Serous Retinopathy

In the non-response group, the SRF leakage resolved spontaneously after more than 6 months in two eyes (22%), although seven eyes required re-treatment (Figure 2). In the recurrence group, recurrent SRF leakage spontaneously resolved in 11 eyes (48%), but 12 eyes required re-treatment. Re-PDT had a 75% response rate (three out of four) in the non-response group and a 100% response rate (six out of six) in the recurrence group (response was defined as resolution of SRF leakage within 6 months of secondary treatment), whereas intravitreal anti-VEGF injection a had 50% response rate (one of two) in the non-response group and a 60% (three of five) response rate in the recurrence group (Figure 4). Combined re-PDT and intravitreal anti-VEGF injection resulted in a 0% response rate in both groups (zero out of one in the nonresponse group, zero out of two in the recurrence group).

Success rate of secondary treatments for the eyes with nonresponse and recurrence. Nonresponse was defined as persistent subretinal fluid (SRF) until 6 months after photodynamic therapy (PDT). Success of the secondary treatment was defined as the SRF resolution achieved in 6 months after the secondary treatment. VEGF = vascular endothelial growth factor.

Figure 4.

Success rate of secondary treatments for the eyes with nonresponse and recurrence. Nonresponse was defined as persistent subretinal fluid (SRF) until 6 months after photodynamic therapy (PDT). Success of the secondary treatment was defined as the SRF resolution achieved in 6 months after the secondary treatment. VEGF = vascular endothelial growth factor.

Discussion

This study showed the long-term results of PDT in the treatment of chronic CSCR. In 85 eyes (90.4%), SRF disappeared in at least 6 months after PDT, although 23 eyes (24.5%) showed recurrence. Unlike previous studies,8,9,14 SFCT was measured using enhanced depth imaging OCT in this study, and smaller reduction in SFCT (HR = 0.951; P = .024) proved to be a statistically significant predictor of CSCR recurrence. Male sex (HR = 10.781; P = .021) and bilateral CSCR (HR = 3.315; P = .008) were associated with recurrence. In the non-response and recurrence groups, re-PDT was effective, despite the initial PDT failure, resulting in a 90% overall success rate.

The visual outcome of PDT in the treatment of chronic CSCR in this study is similar to those reported previously.5,15,16 Lai et al. reported a BCVA of 0.16 logMAR (Snellen equivalent: 20/28) at the last visit and a total logMAR improvement of 0.21 (136 eyes; mean follow-up: 57.7 months). Haga et al. reported a BCVA of 0.08 logMAR (Snellen equivalent: 20/24) at the last visit and a total improvement of 0.13 logMAR (79 eyes; mean follow-up period: 50.1 months). In the current study, BCVA at the last visit was 0.19 ± 0.36 logMAR (Snellen equivalent: 20/31), and improvement in visual acuity throughout the entire follow-up period was 0.15 ± 0.31 logMAR (ETDRS equivalent: 7.5 letters).

Shin et al. reported that both conventional and half-fluence PDT cause choriocapillary hypoperfusion and retinal thinning, although this effect is less severe in half-fluence PDT.7 In the present long-term study, PDT caused no severe subfoveal choroidal thinning; that is, the mean SFCT had decreased by only 17% at the last visit (335.3 ± 93.1 μm) compared with the initial visit (404.8 μm ± 100.5 μm).

In terms of response and recurrence, Lai et al. reported that a single PDT treatment completely resolved serous retinal detachment in 97.1% of eyes 36 months after treatment, and that the disease recurred in 2.9% of the eyes. Haga et al. reported complete absorption of SRF leakage in 94% of eyes, incomplete absorption in 6% of eyes, and recurrence of SRF leakage in 13% of eyes.11 In the present study, 23 of 94 eyes (24%) showed recurrence of SRF leakage, whereas previous long-term studies into PDT for chronic CSCR reported a proportion of only 2.9% to 19%.9,11,13 This discrepancy can be attributed to selection bias, whereby patients with recurrence tend to visit the clinic for longer periods, as well as to the PDT method applied. In terms of the PDT method applied, there were no significant differences between the various PDT methods in terms of response and recurrence (Tables 3 and 4).

Unlike previous studies, which have defined unsuccessfulness as the sum of non-response (incomplete resolution of SRF leakage) and recurrence, we divided the patients and analyzed them separately to clarify the risk factors for recurrence. The Cox proportional hazard model ascertained that male sex (HR = 10.781; P = .021), bilateral CSCR (HR = 3.315; P = .008), and smaller reduction in choroidal thickness (HR = 0.951; P = .024) were potential risk factors for recurrence. Previous studies have reported bilateral CSCR and SFCT reduction as risk factors except male sex.9,10,15 With regard to the association between bilateral CSCR and recurrence, we suggest that patients with bilateral CSCR may be harder to treat than patients with unilateral CSCR. Bilateral CSCR is often found in atypical cases that manifest a rapidly aggravating course and are often combined with systemic diseases.17–20 Smaller reduction of SFCT was another significant risk factor in the present study. Kim et al. suggested that smaller reduction of choroidal thickness may indicate that PDT did not affect the choroid enough to fully resolve the abnormal choroidal vasculopathy.10 SFCT at one month after the PDT could be used as potential predictors for recurrences and nonresponses. With regard to the association between male sex and recurrence, Lai et al. previously reported that the recurrence rate in men was lower than in women (HR = 0.90),21 which is contrary to ours. High psychosocial burden of males in South Korea may provide a clue for our result,15,22 which may lead to the susceptibility to recurrence of CSCRs. This requires further research.

Two eyes (2%) developed CNV after the initial PDT. One was a case of 51-year-old male, who developed new-onset visual disturbance 2 years after half-fluence PDT. In his OCT, FA, and ICGA images, type 1 CNV with PCV and SRF was found. The SRF disappeared after the intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) treatment without recurrence. The other one was a case of 46-year-old male showed new classic, type 2 CNV 1 month after standard PDT. The CNV was identified with OCT and FA and it was resolved after the intravitreal bevacizumab treatment. The CNV in the first case might have been identified pre-PDT if we have used OCT angiography at the pre-treatment stage, because OCT angiography has been shown to detect the hidden type 1 CNVs, which FA and ICG might miss.23–26 Thus, it could be the natural course of chronic CSC, rather than a complication of PDT. However, the second case can be regarded as a complication of PDT, because the CNV was found just 1 month after PDT and it was type 2 CNV, arising through the defect in the Bruch's membrane, like the previously reported case.27

The limitations of the present study include its retrospective design and the small population. Selection and attrition bias may have occurred because patients without recurrence are less likely to re-visit the clinic, Hence, the rate of recurrence and non-response may have been overestimated in the present study. Nevertheless, this study included long-term follow-up data including choroidal thickness, as well as analysis of the outcome of secondary treatment.

In conclusion, verteporfin PDT for the treatment of CSCR showed good efficacy in terms of visual and anatomical outcomes, as well as good safety results, in a long-term follow-up. Although disease recurred in about one-fifth of eyes, re-treatment using additional PDT resulted in a good response rate.

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Demographics, Pre-Treatment Clinical Features, and Treatment Variables of Subjects

DemographicsResults

Total number of eyes and patients94 eyes of 87 patients

Age at first PDT47.9 ± 7.1 (32.6–76.6) years

Follow-up period58.1 ± 20.3 (36.1–142.6) months

Male64 (68%)

Diabetes mellitus6 (6%)

Hypertension12 (13%)

Steroid-induced4 (4%)

Pre-Treatment Clinical FeaturesResults

Laterality (right eye)40 (43%)

Bilateral CSC29 (31%)

Refractive error (SE)−0.32 ± 1.66 (−5.75 to +6.13) diopters

Pseudophakia1 (1%)

Time span since the onset till the first PDT8.4 ± 10.2 (0.3–62.8) months

Previous treatment before PDT9 (10%)
  Focal laser2 (2%)
  Oral acetazolamide tablet7 (7%)

Pre-treatment best-corrected visual acuity*0.55 ± 0.27 logMAR

Pre-treatment central macular subfield thickness371.8 ± 117.5 µm

Pre-treatment subfoveal choroidal thickness404.8 ± 100.5 µm

Retinal pigment epithelial atrophy8 (9%)

Retinal pigment epithelial detachment12 (13%)

Treatment VariablesResults

Total count of PDT1.2 ± 0.4 (1–3)
  Once79 (84%)
  Twice13 (14%)
  Three times2 (2%)

Fluence and dose
  Half-fluence with standard dose76 (90%)
  Full-fluence with half dose12 (13%)
  Full-fluence with standard dose6 (6%)

Area treated with PDT (×106 π µm2)2.09 ± 2.03 (0.36–13.50)

Treatments covering fovea83 (87%)

Treatment Outcomes Before and After the Initial PDT in Chronic Central Serous Retinopathy

Time After the Initial PDTPresence of SRF (n, %)BCVA (logMAR)CSMT (µm)SFCT (µm)*Cumulative Incidence of CNV (n, %)
Pre-treatment (n = 94)94 (100%)0.34 ± 0.33371.8 ± 117.5404.8 ± 100.5
1 month (n = 94)22 (23%)0.28 ± 0.33222.0 ± 53.0356.3 ± 97.31 (1%)
6 months (n = 94)12 (13%)0.19 ± 0.28233.7 ± 66.6346.2 ± 105.8
12 months (n = 94)13 (14%)0.16 ± 0.27233.5 ± 41.9341.7 ± 102.7
24 months (n = 94)11 (12%)0.18 ± 0.31238.5 ± 69.12 (2%)
36 months (n = 94)13 (14%)0.19 ± 0.35241.5 ± 73.6
48 months (n = 71)11 (15%)0.18 ± 0.32230.1 ± 35.4
60 months (n = 38)6 (16%)0.16 ± 0.24240.7 ± 51.6
At the final visit (mean 58.1 months, n = 94)10 (11%)0.19 ± 0.36236.0 ± 66.3335.3 ± 93.1*2 (2%)

Risk Factors for Non-Response Until 6 Months After the Photodynamic Therapy for Chronic Central Serous Retinopathy*

VariablesNon-Response (n = 9)Initial Response (n = 85)PaStepwise Multiple Logistic Regression AnalysisP
OR (Range With 95% CI)
Age at first PDT (year)54.4 ± 9.647.3 ± 6.5.0271.215 (1.049–1.408).009
Sex (male)3 (33%)61 (72%).027NM
Diabetes mellitus1 (11%)5 (6%).463NM
Hypertension2 (22%)10 (12%).322NM
Steroid-induced CSC04 (5%)1.000NM
Refractive error (SE, diopters)−0.11 ± 2.21−0.35 ± 1.61.689NM
Bilateral CSC2 (22%)27 (32%).716NM
Pre-treatment BCVA (logMAR)0.43 ± 0.230.33 ± 0.34.099NM
OCT ParametersNM
Pre-treatment CSMT (µm)398.9 ± 79.7368.9 ± 120.8.470NM
Reduction of CSMT for the first month (%)25.0 ± 16.737.3 ± 18.6.0600.939 (0.892–0.989).017
Pre-treatment SFCT (µm)247.8 ± 190.1 (11%)316.6 ± 193.7.312NM
Reduction of SFCT for the first month, (%)4.6 ± 6.39.5 ± 11.8.220NM
Treatment VariablesNM
Time duration from symptom onset to the first PDT (month)7.60 ± 5.448.46 ± 10.56.616NM
Area treated with PDT (×106 π µm2)7.60 ± 5.4410.56 ± 8.46.199NM
Dose and FluenceNM
Half-fluence with standard dose9 (100%)67 (79%).268NM
Full-fluence with half dose012 (14%).276NM
Full-fluence with standard dose06 (7%).537NM

Risk Factors for Recurrence After Photodynamic Therapy for Chronic Central Serous Retinopathy*

VariablesRecurrence (n = 23)No Recurrence (n = 62)PaStepwise Multiple Logistic Regression Analysis**PCox Proportional Hazard Model Survival Analysis**P


OR (Range with 95% CI)HR (Range with 95% CI)

Age at the first PDT (year)48.8 ± 7.046.7 ± 6.2.086NMNM

Sex (male)22 (96%)39 (63%).00320.417 (2.260–184.466).00710.781 (1.442–80.581).021

Diabetes mellitus1 (4%)4 (6%)1.000NMNM

Hypertension1 (4%)9 (15%).274NMNM

Steroid-induced CSC0 (0%)4 (6%).570NMNM

Refractive error (SE, diopters)−0.46 ± 1.94−0.31 ± 1.48.532NMNM

Bilateral CSC11 (48%)16 (23%).0533.407 (1.010–11.491).0483.315 (1.370–8.020).008

Pre-treatment BCVA (logMAR)0.40 ± 0.490.31 ± 0.26.905NMNM

OCT Parameters
  Pre-treatment CSMT (µm)357.4 ± 114.1373.2 ± 123.8.514NMNM
  Reduction of CSMT for the first month§§ (%)34.9 ± 19.238.2 ± 18.5.472NMNM
  Pre-treatment SFCT (µm)406.7 ± 106.0408.2 ± 103.7.959NMNM
  Reduction of SFCT for the first month, (%)6.1 ± 8.312.6 ± 12.5.0230.936 (0.883–0.993).0280.951 (0.911–0.993).024
  Persistent subretinal fluid after a month5 (22%)10 (16%).537NMNM

Treatment Variables
  Time duration from symptom onset to the first PDT (month)11.7 ± 17.07.3 ± 6.6.583NMNM
  Area treated with PDT (x106 π µm2)1.41 ± 0.652.42 ± 2.35.0440.515 (0.263–1.005).052NM
  Dose and fluence
    Half-fluence with standard dose21 (91%)46 (74%).134NMNM
    Full-fluence with half dose2 (9%)10 (16%).499NMNM
    Full-fluence with standard dose0 (0%)6 (10%).184NMNM
Authors

From the Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea (YJP, KHP, SJW); and the Department of Ophthalmology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea (YKK).

The authors report no relevant financial disclosures.

Supported by the National Research Foundation of Korea grant 2016R1D1A1B03934724 and funded by the Korean government (Ministry of Science, ICT and Future Planning; MSIP) and a research grant from Seoul National University Bundang Hospital (13-2019-003). The funding organization had no role in the design or conduct of this study.

Address correspondence to Se Joon Woo, MD, PhD, Department of Ophthalmology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea 13620; email: sejoon1@snu.ac.kr.

Received: January 01, 2019
Accepted: June 10, 2019

10.3928/23258160-20191119-03

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