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Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC., Competing Interests: Declaration of competing interest Bailey Freund is an consultant for Bayer, Genentech, Heidelberg Engineering, Nidek, Novartis, Regeneron, and Zeiss. The author authors declare not to have conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: We performed a multicenter, retrospective study on patients with bilateral chronic central serous chorioretinopathy (cCSC) who received single-session bilateral reduced-settings photodynamic therapy (ssbPDT) and assessed anatomical (resolution of subretinal fluid [SRF]) and functional (best-corrected visual acuity [BCVA]) outcomes and safety., Methods: Patients who underwent ssbPDT between 01/01/2011 and 30/09/2022 were included. The resolution of SRF at first, second, and final follow-up was assessed on optical coherence tomography (OCT), and BCVA measurements were collected at these visits. When fovea-involving ssbPDT was performed, ellipsoid zone (EZ) and external limiting membrane (ELM) integrity was graded before and after treatment., Results: Fifty-five patients were included in this study. Sixty-two of hundred and eight eyes (56%) showed a complete resolution of SRF at the first follow-up, which increased to 73/110 (66%) at the final follow-up. The mean logMAR BCVA improved by -0.047 ( P = 0.02) over follow-up. EZ integrity increased from 14/21 (67%) to 24/30 (80%) while ELM integrity increased from 22/30 (73%) to 29/30 (97%)., Conclusion: Patients with cCSC with bilateral SRF at baseline showed significant anatomical and functional improvements after ssbPDT, both at short-term and long-term follow-up. No relevant adverse events were noted., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: A retrospective study was performed with data from the prospective randomized controlled trials, PLACE and SPECTRA, assessing the risk of foveal atrophy and the likelihood of structural and functional improvement on optical coherence tomography, after foveal half-dose photodynamic therapy in chronic central serous chorioretinopathy., Methods: A total of 57 chronic central serous chorioretinopathy patients received a single half-dose photodynamic therapy with a treatment spot that included the fovea. Optical coherence tomography scans and fundus autofluorescence images were analyzed for structural improvement and possible atrophy development, at baseline and at several visits after treatment. Main outcome measures were integrity of the external limiting membrane and ellipsoid zone on optical coherence tomography and hypoautofluorescence on fundus autofluorescence., Results: The subfoveal external limiting membrane was graded as continuous in 21 of 57 of patients (36.8%) at baseline, and the subfoveal ellipsoid zone was graded as continuous in 5 of 57 patients (8.8%) at first visit, which improved to 50 of 51 (98.0%) and 32 out of 51 (62.7%) at the final visit at 2 years, respectively (both P < 0.001). Hypoautofluorescent changes on fundus autofluorescence were present in 25 of 55 patients (45.5%) at baseline and in 23 of 51 patients (45.1%) at the final visit ( P = 0.480)., Conclusion: In patients with chronic central serous chorioretinopathy who received a single, foveal, half-dose photodynamic therapy, a significant improvement in structure and function was seen at the final follow-up. None of the patients developed foveal atrophy., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Treatment of chronic central serous chorioretinopathy (cCSC) remains a topic of controversy. As cCSC is a disease that can wax and wane, treatment efficacy is difficult to assess especially when trials compare active treatments without any placebo/control group. In this study, we systematically reviewed short-term efficacies of any cCSC treatment tested in randomized controlled trials (RCT) and employed network meta-analyses to compare to non-treatment controls. We searched 11 literature databases on 20 March 2022 for RCTs of treatment of cCSC. We identified 17 RCTs including a total of 1172 eyes. Treatments included conventional laser (44 eyes), half-dose or half-fluence photodynamic therapy (PDT) (298 eyes), ranibizumab (16 eyes), antioxidants (50 eyes), mineralocorticoid receptor antagonists (187 eyes), rifampicin (91 eyes), selective retina therapy (SRT) (67 eyes) and subthreshold micropulse laser (192 eyes). Compared with controls, significant benefit on complete subretinal fluid resolution was only obtained from half-dose or half-fluence PDT (OR: 20.6; 95% CI: 6.3-66.7; p < 0.0001) and conventional laser (OR: 36.4; 95% CI: 2.0-655.7; p = 0.015), and at an order of magnitude lower degree from SRT (OR: 3.4; 95% CI: 1.7-6.8; p = 0.00075). Compared with controls and after sensitivity analyses, significant benefit in the change in best-corrected visual acuity was only obtained by half-dose/-fluence PDT (-0.13 logMAR; 95% CI: -0.20 to -0.06 logMAR; p = 0.00021). In conclusion, three treatment options provide significant improvement over no treatment: half-dose/-fluence PDT, conventional laser and to a much lesser degree SRT. Considering that conventional laser can only be applied for extrafoveal leaks, and the long-term data available for PDT-based treatments finding persisting treatment results, half-dose or half-fluence PDT is the only viable treatment option for patients with cCSC. Shortage issues with verteporfin should not lead to employment of ineffective treatment modalities, as they put patients at unnecessary risk of adverse events., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Comparing anatomic and functional efficacy and safety of primary treatment with either half-dose photodynamic therapy (PDT) or oral eplerenone, or crossover treatment in chronic central serous chorioretinopathy patients., Methods: After the SPECTRA trial baseline visit, patients were randomized to either half-dose PDT or eplerenone and received crossover treatment if persistent subretinal fluid (SRF) on optical coherence tomography (OCT) was present at first follow-up (at 3 months). Presence of SRF and best-corrected visual acuity (BCVA) was evaluated at 12 months., Results: Out of the 90 patients evaluated at 12 months, complete SRF resolution was present on OCT in 43/48 (89.6%) of patients who were primarily randomized to half-dose PDT and in 37/42 (88.1%) who were primarily randomized to eplerenone. Out of the 42 patients that were primarily randomized to eplerenone, 35 received crossover treatment with half-dose PDT. The BCVA improved significantly more at 12 months in patients who had received primary half-dose PDT as compared to the primary eplerenone group (p = 0.030)., Conclusions: Twelve months after baseline visit, most patients treated with half-dose PDT (either primary or crossover treatment) still had complete SRF resolution. The long-term BCVA in patients who receive primary half-dose PDT is better than in patients in whom PDT is delayed due to initial eplerenone treatment with persistent SRF., (© 2022. The Author(s).)

Introduction: Since July 2021, a worldwide shortage of verteporfin (Visudyne®) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first-choice treatment or regarded as a major treatment option., Materials and Methods: A questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage., Results: Our questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries., Conclusion: The shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public-private partnerships., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To compare the efficacy and safety of crossover treatment to half-dose photodynamic therapy (PDT) and eplerenone treatment after the failure of primary treatment in patients with chronic central serous chorioretinopathy (cCSC)., Design: Multicenter crossover clinical trial., Subjects: At 3 months after the baseline visit of the SPECTRA (Half-Dose Photodynamic Therapy Versus Eplerenone: Treatment Trial for Chronic Central Serous Chorioretinopathy) randomized controlled trial, either half-dose PDT or eplerenone treatment was evaluated for each patient, and patients who still demonstrated subretinal fluid (SRF) were included in the current study, the SPECS (Central Serous Chorioretinopathy Treated with Half-Dose PDT or Eplerenone Crossover Study) trial., Methods: At the baseline visits for the current SPECS trial, crossover treatment was performed for patients who still demonstrated SRF. These patients received either half-dose PDT or oral eplerenone for 12 weeks. Both anatomic and functional parameters were evaluated 3 months after crossover treatment., Main Outcome Measures: Complete resolution of SRF on OCT., Results: Forty-nine patients were included in the SPECS trial (38 received primary eplerenone treatment; 11 received half-dose PDT). At 3 months after crossover treatment, 32 of 37 (86.5%) in the crossover to half-dose PDT group and 2 of 9 (22.2%) in the crossover to eplerenone group had complete SRF resolution (P = 0.030). The mean foveal sensitivity increased significantly more in the crossover to half-dose PDT group (mean, +3.08 dB) compared with the crossover to eplerenone group (mean, -0.27 dB; P = 0.009)., Conclusions: Patients with cCSC with the persistence of SRF after primary eplerenone treatment can benefit from half-dose PDT, which can induce a relatively fast and complete SRF resolution, along with an improvement in foveal sensitivity., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Comparing the effect of half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment on retinal pigment epithelial detachments (PEDs) in chronic central serous chorioretinopathy., Methods: This study included data from the PLACE trial, a prospective randomized controlled trial comparing half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment in chronic central serous chorioretinopathy. Main outcome measurements were changes in both the foveal PED and the highest PED within the macula at baseline compared with first and final evaluation visit., Results: At baseline, a macular PED was detected in 76.9% of patients (123/160), and a PED within 1,500 µm from the foveal center in 37.5% of patients (60/160). In the half-dose photodynamic therapy arm (61 patients), there was a significantly larger decrease in the highest macular PED compared with the high-density subthreshold micropulse laser treatment arm (62 patients) at both first and final evaluation visits (P < 0.001 and P = 0.012, respectively). The decrease of highest foveal PED was significant at first visit (P = 0.025)., Conclusion: Half-dose photodynamic therapy is superior to high-density subthreshold micropulse laser treatment with regard to a statistically significant reduction in the height of macular PEDs in active chronic central serous chorioretinopathy. These findings may also have implications for other diseases within the pachychoroid disease spectrum that can present with PEDs.

Background: To investigate the anatomical and functional results in eyes with peripapillary pachychoroid syndrome (PPS) undergoing photodynamic therapy (PDT)., Methods: A total of 25 eyes from 23 patients with PPS treated with PDT were retrospectively evaluated in this multicentric study. Main outcome measure was the proportion of eyes that achieved treatment success, defined as a decrease in both subretinal fluid (SRF) height and central subfield thickness (CST), at 3 months after PDT compared to baseline. Secondary outcomes were the change in CST, SRF, and best-corrected visual acuity (BCVA) 3 months after treatment and predictive factors for treatment success. When available, data between 3 and 12 months were also reviewed., Results: Treatment success was achieved in 16 eyes (64%). In the total cohort, CST decreased significantly from 356 ± 118 µm at baseline to 282 ± 90 µm and 270 ± 91 µm at 1 and 3 months, respectively (p < 0.001). Maximal SRF height decreased significantly from 102 ± 83 µm at baseline to 38 ± 46 µm and 32 ± 42 µm at 1 and 3 months, respectively (p < 0.001), and remained stable at month 6 (29 ± 44 µm) and month 12 (23 ± 35 µm). BCVA improved significantly from baseline to month 3 (p = 0.021)., Conclusions: PDT can be considered an efficacious treatment option in patients with PPS. Prospective data with longer follow-up in a bigger cohort are needed in order to determine the optimal treatment algorithm in this relatively novel disease., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To explore subretinal fluid (SRF) morphology in chronic central serous chorioretinopathy (cCSC) after one session of either high-density subthreshold micropulse laser (HSML) treatment or half-dose photodynamic therapy (PDT)., Methods: We retrospectively obtained optical coherence tomography (OCT) scans from a subset of patients from a randomized controlled trial on treatment-naïve eyes with cCSC allocated to either HSML treatment or half-dose PDT. OCT scans were evaluated prior to treatment and 6-8 weeks post-treatment, where we measured maximum SRF height and width, calculated the maximum height-to-maximum width-ratio (maxHWR) and calculated the total SRF volume., Results: Forty-one eyes of 39 cCSC patients were included. SRF morphology ranged from flat to dome-shaped, quantified as maxHWR ranging between 0.02 and 0.12. SRF volume was median 0.373 μl (range: 0.010-4.425 μl) and did not correlate to maxHWR (rho = -0.004, p = 0.982). Half-dose PDT was superior to HSML treatment in complete SRF resolution (RR = 3.28, p = 0.003) and in morphological changes of SRF (Δ maximum height , p = 0.001; Δ maximum width , p < 0.001; Δ volume , p = 0.025). SRF resolved completely in 19/22 PDT-treated eyes (86%) and 5/19 HSML-treated eyes (26%). SRF volume increased in five eyes (26%) after HSML treatment, and in none of the eyes after half-dose PDT. SRF morphology at baseline did not predict treatment outcomes., Conclusion: SRF morphology changed after both HSML treatment and half-dose PDT in cCSC, with SRF disappearing in most PDT-treated patients, whereas SRF volume increased in a sizeable proportion of HSML-treated patients. Baseline SRF characteristics measured in this study were unable to predict outcomes after either HSML treatment or half-dose PDT., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To compare the efficacy and safety between half-dose photodynamic therapy (PDT) and eplerenone therapy for treating chronic central serous chorioretinopathy (cCSC)., Design: This was a multicenter, open-label, randomized controlled trial., Methods: This investigator-initiated trial was conducted in 3 academic medical centers in the Netherlands. Eligible patients were randomized at a 1:1 ratio to receive either indocyanine green angiography-guided half-dose PDT or oral eplerenone for 12 weeks. Both anatomical and functional outcomes were evaluated at 3 months after the start of treatment., Results: A total of 107 patients were randomly assigned to receive either half-dose PDT (n = 53) or eplerenone treatment (n = 54). Thirteen patients (3 in the PDT group and 10 in the eplerenone group) did not adhere to the study protocol. At the 3-month evaluation visit, 78% of patients in the PDT group had complete resolution of subretinal fluid accumulation compared to only 17% of patients in the eplerenone group (P < .001). Mean best-corrected visual acuity in Early Treatment of Diabetic Retinopathy Study letters at the 3-month evaluation visit was 83.7 ± 10.8 and 82.8 ± 9.0 in the PDT and eplerenone groups, respectively (P = .555). In addition, mean retinal sensitivity on microperimetry was 25.4 ± 3.4 dB and 23.9 ± 4.0 dB in the PDT and eplerenone groups, respectively (P = .041). Finally, mean vision-related quality of life scores were 87.2 ± 8.5 and 83.8 ± 12.1 in the PDT and eplerenone groups, respectively (P = .094). Three patients (6%) in the PDT group experienced adverse events during the study compared to 18 patients (33%) in the eplerenone group., Conclusions: Half-dose PDT is superior to oral eplerenone for cCSC with respect to both short-term safety and efficacy outcomes., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To describe the treatment outcomes and recurrence risk of chronic central serous chorioretinopathy (cCSC) in patients who had complete resolution of subretinal fluid (SRF) after either primary half-dose photodynamic therapy (PDT) or high-density subthreshold micropulse laser (HSML) in the PLACE trial., Methods: This multicentre prospective follow-up study evaluated cCSC patients at 1 year after completion of the PLACE trial. Outcomes included: complete resolution of SRF on OCT, best-corrected visual acuity (BCVA) in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, retinal sensitivity on microperimetry and a visual function questionnaire (NEI-VFQ25)., Results: Twenty-nine out of 37 patients who received half-dose PDT and 15 out of 17 patients who received HSML could be evaluated at final visit. At final visit, 93% of the patients treated with half-dose PDT had complete resolution of SRF, compared with 53% of HSML-treated patients (p = 0.006). At final visit, the mean estimate increase in the PDT group compared with the HSML group was + 2.1 ETDRS letters, +0.15 dB for the retinal sensitivity and + 5.1 NEI-VFQ25 points (p = 0.103, p = 0.784 and p = 0.071, respectively). The mean estimated central retinal thickness in the half-dose PDT group was -7.0 µm compared with the HSML group (p = 0.566). The mean estimated subfoveal choroidal thickness in the half-dose PDT group was -16.6 µm compared with the HSML group (p = 0.359)., Conclusion: At 20 months after treatment, cCSC patients successfully treated with half-dose PDT are less likely to have recurrences of SRF compared with those successfully treated with HSML. However, functional outcomes did not differ., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To compare the effects of half-dose photodynamic therapy (PDT) and high-density subthreshold micropulse laser on choroidal dysfunction evaluated by degree and extent of hyperfluorescence on indocyanine green angiography (ICGA) in chronic central serous chorioretinopathy., Methods: Data from the multicenter, randomized, controlled PLACE trial were used in this study. Hyperfluorescent and hypofluorescent areas on ICGA, their association with subretinal fluid and visual function were assessed., Results: In total, 146 patients were included (72 in the PDT and 74 in the high-density subthreshold micropulse laser treatment arm). A significantly greater decrease in the size of hyperfluorescent areas on ICGA at first visit after treatment was seen after PDT compared with high-density subthreshold micropulse laser (mean, -1.41 ± 2.40 mm2 vs. -0.04 ± 0.73 mm2, respectively; P < 0.001). A reduction in the degree of hyperfluorescence on ICGA decreased the odds of having persistent subretinal fluid on optical coherence tomography at first visit after treatment (B = 0.295; P = 0.019). There were no significant differences in best-corrected visual acuity and retinal sensitivity between the subgroup with novel hypofluorescence (n = 20, 28%) on ICGA at first visit post PDT, compared with the subgroup without novel hypofluorescence on ICGA after PDT., Conclusion: Choroidal abnormalities in chronic central serous chorioretinopathy can be effectively treated by ICGA-guided half-dose PDT but not with high-density subthreshold micropulse laser application.

Purpose: To evaluate the clinical outcomes after half-dose photodynamic therapy (PDT) in chronic central serous chorioretinopathy (cCSC) patients with pre-existent fovea-involving atrophy., Methods: In this retrospective study, cCSC patients who had a window defect of the retinal pigment epithelium (RPE) on fluorescein angiography (FA), compatible with RPE atrophy, prior to half-dose PDT were included., Results: Thirty-four cCSC eyes with typical findings of cCSC on multimodal imaging, and fovea-involving RPE atrophy on FA, were included. At the first visit after PDT (at a median of 1.8 months after half-dose PDT), 20 eyes (59%) had a complete resolution of SRF (p < 0.001), while this was the case in 19 eyes (56%) at final visit (median of 11.3 months after half-dose PDT; p < 0.001). The mean BCVA in Early Treatment of Diabetic Retinopathy Study letters was 71. 2 ± 15.9 at last visit before PDT, which increased to 74.1 ± 14.1 at first visit after PDT (p = 0.093, compared with baseline), and changed to 73.0 ± 19.1 at final visit (p = 0.392, compared with baseline). Both at first visit after PDT and at final visit, a significant decrease in subfoveal choroidal thickness was observed (p = 0.032 and p = 0.004, respectively)., Conclusions: Half-dose PDT in cCSC patients with pre-existing fovea-involving atrophy may lead to anatomical changes, but not to functional improvements. Ideally, cCSC should be treated with half-dose PDT before the occurrence of such atrophy.

Purpose: To study the early anatomic choroidal alterations in eyes with chronic central serous chorioretinopathy (CSCR) undergoing photodynamic therapy (PDT)., Design: Multicenter retrospective cohort study., Methods: A total of 77 patients and 81 eyes with chronic CSCR treated with PDT and 64 untreated fellow eyes were evaluated. Central macular thickness (CMT) and choroidal features including subfoveal choroidal thickness (SFCT), total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were analyzed. Choroidal vascularity index (CVI) was calculated in all study eyes at baseline and at 1- and 3-months post-PDT., Results: In eyes receiving PDT, Snellen visual acuity (VA) significantly improved at months 1 and 3 (P < .001). CMT and SFCT showed a significant reduction from baseline at months 1 and 3 (P < .001), whereas TCA and LCA showed a significant decrease only at the 1-month follow-up visit. Baseline mean TCA and LCA were 2.30 ± 1.41 mm 2 and 1.23 ± 0.73 mm 2 , respectively, and decreased to 2.07 ± 1.21 mm 2 and 1.08 ± 0.63 mm 2 at the 1-month follow-up visit, respectively (P = .01). No significant changes were recorded for SCA and CVI. In the fellow eye group, VA, CMT, and all choroidal parameters showed no differences between baseline and any follow-up visits (all P > .05)., Conclusions: After PDT for chronic CSCR we observed sustained reductions in CMT and SFCT, while reductions in TCA and LCA were only noted at the 1-month follow-up interval. These choroidal parameters may provide additional quantitative biomarkers to evaluate the anatomic response to therapy but await further prospective validation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To assess whether chronic central serous chorioretinopathy (cCSC) patients without a complete resolution of subretinal fluid (SRF) after either half-dose photodynamic therapy (PDT) or high-density subthreshold micropulse laser (HSML) treatment may benefit from crossover treatment., Design: Multicenter prospective interventional case series., Methods: cCSC patients with persistent SRF at the final visit of the PLACE trial were included. Patients received crossover treatment with either half-dose PDT or HSML., Results: Thirty-two patients received PDT and 10 patients received HSML. At the first evaluation visit (6-8 weeks after treatment), 81% of patients in the PDT group had complete resolution of SRF, while none of the HSML-treated patients had complete resolution of SRF. At final visit (1 year after baseline), 78% (P = .030) and 67% (P = .109) of the patients, respectively, had a complete resolution of SRF. The mean retinal sensitivity in the PDT group increased from 21.7 dB (standard error [SE]: 0.9) to 23.4 dB (SE: 0.8) at evaluation visit 1 (P = .003), to 24.7dB (SE: 0.8) at final visit (P < .001), while there were no significant changes in the HSML group (23.7 dB [SE: 1.6] at baseline, 23.8 dB [SE: 1.4] at evaluation 1, and 23.3 dB [SE: 1.4] at final visit). The mean visual acuity and mean visual quality-of-life questionnaire score did not change significantly in both groups., Conclusions: Crossover to half-dose PDT after previous unsuccessful HSML treatment for cCSC may lead to improved anatomic and functional endpoints, while crossover to HSML after half-dose PDT does not seem to significantly affect these endpoints., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess whether treatment of chronic central serous chorioretinopathy (cCSC) with photodynamic therapy (PDT) and high-density subthreshold micropulse laser (HSML) results in choroidal vascularity index (CVI) changes that may account for the treatment effect., Methods: Patients with cCSC were prospectively included and analyzed. Patients received either half-dose PDT or HSML treatment. CVI of the affected and unaffected eye was obtained before treatment, 6 to 8 weeks after treatment, and 7 to 8 months after treatment., Results: At baseline, 29 eyes (29 patients) were included both in the PDT and in the HSML group. The mean (± standard deviation) CVI change in the HSML group between before PDT and 6 to 8 weeks after PDT was - 0.009 ± 0.032 (p = 0.127), whereas this was 0.0025 ± 0.037 (p = 0.723) between the visit before PDT and final visit. The patients in the PDT group had a CVI change of - 0.0025 ± 0.037 (p = 0.723) between the visit before PDT and first visit after PDT, and a mean CVI change of - 0.013 ± 0.038 (p = 0.080) between the visit before PDT and final visit. There was no significant correlation between CVI and BCVA at the measured time points, in both the HSML group (p = 0.885), and in the PDT group (p = 0.904). Moreover, no significant changes in CVI occurred in the unaffected eye at any time point., Conclusions: PDT and HSML do not significantly affect CVI, and therefore a CVI change may not be primarily responsible for the treatment effect. The positive treatment effect of both interventions may rely on other mechanisms, such as an effect on choriocapillaris and/or retinal pigment epithelium function.

Purpose: To compare the outcome between high-density subthreshold micropulse laser (HSML) treatment and half-dose photodynamic therapy (PDT) in chronic central serous chorioretinopathy (cCSC) patients, subdivided based on either focal or diffuse leakage on fluorescein angiography (FA)., Design: Retrospective analysis of multicenter randomized controlled trial data., Methods: Patients were treated with either half-dose PDT or HSML (both indocyanine green angiography-guided) and categorized in 2 groups, based on focal or diffuse leakage on FA. Clinical outcomes were evaluated at baseline and during follow-up., Results: In the focal leakage group (63 patients), both at first evaluation and at final visit, more PDT-treated than HSML-treated patients demonstrated a resolution of subretinal fluid (evaluation visit 1: 57% in the PDT group and 17% in the HSML group, P = .007; final visit: 75% and 38%, P = .012). In the diffuse leakage group (93 patients), both at first evaluation and at final visit, more PDT-treated than HSML-treated patients showed a resolution of subretinal fluid (evaluation visit: 1:48% in the PDT group and 16% in the HSML group, P = .002; final visit: 67% and 21%, P = .002). PDT-treated patients in the focal and diffuse leakage group had a higher retinal sensitivity increase, comparing baseline and final visit (+3.1 ± 3.1 dB vs +1.2 ± 4.0 dB, P = .048, and +2.7 ± 3.3 dB vs +1.0 ± 3.8 dB, P = .036, respectively). Only in the diffuse leakage group, the increase in ETDRS letters was higher in the PDT-treated group when comparing baseline and first evaluation visit (+4.4 ± 6.1 vs +0.9 ± 10.0, P = .049)., Conclusions: Half-dose PDT is superior to HSML treatment in cCSC patients, regardless of the presence of focal or diffuse leakage on FA., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To compare the anatomic and functional efficacy and safety of half-dose photodynamic therapy (PDT) versus high-density subthreshold micropulse laser (HSML) treatment in patients with chronic central serous chorioretinopathy (cCSC)., Design: Open-label, multicenter, randomized controlled clinical trial., Participants: Patients with cCSC whose disease had to be confirmed by both clinical characteristics and findings on multimodal imaging., Methods: Eligible patients were randomized in a 1:1 allocation ratio. Treatment was evaluated during a follow-up visit, and the same treatment was repeated in patients who still demonstrated subretinal fluid (SRF)., Main Outcome Measures: The primary end point was the complete disappearance of SRF at the first evaluation visit at 6 to 8 weeks after treatment. As a secondary outcome measure, we assessed this anatomic result at the final evaluation visit at 7 to 8 months after treatment. Other secondary outcomes covered functional improvement and included change in best-corrected visual acuity (BCVA; measured in Early Treatment Diabetic Retinopathy Study [ETDRS] letters), retinal sensitivity (measured using microperimetry), and vision-related quality of life using a validated questionnaire., Results: Between November 2013 and September 2016, 179 patients were included: 89 patients were assigned randomly to half-dose PDT, and 90 were assigned randomly to HSML treatment. At their first evaluation visit, SRF had resolved in 51.2% and 13.8% of patients, respectively (P < 0.001). At their final evaluation visit, a significantly higher percentage of PDT-treated patients demonstrated no SRF (67.2% vs. 28.8%; P < 0.001). Moreover, at the first evaluation visit, the PDT-treated patients showed a significantly higher increase in BCVA (+4.60±6.62 ETDRS letters vs. +1.39±8.99 ETDRS letters; P = 0.011), and a significantly higher increase in retinal sensitivity on microperimetry (+2.01±3.04 dB vs. +0.92±3.65 dB; P = 0.046); however, the improvement in vision-related quality of life was similar (score of +2.87±8.35 vs. +2.56±7.36, respectively; P = 0.800)., Conclusions: Half-dose PDT is superior to HSML for treating cCSC, leading to a significantly higher proportion of patients with complete resolution of SRF and functional improvement., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the short-term outcome of and possible temporary vision loss after half-dose verteporfin photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (cCSC)., Methods: In this prospective study, 14 eyes of 13 cCSC patients who underwent half-dose PDT were included. Patients received spectral-domain optical coherence tomography (OCT) imaging and microperimetry before PDT on the day of treatment and 1 week after treatment., Results: Five patients (38%) reported worsening of visual complaints in the week after half-dose PDT. No significant changes in both central foveal thickness, height of subretinal fluid, and choroidal thickness on optical coherence tomography imaging and retinal sensitivity on microperimetry were observed, neither in the patients who did not experience worsening of visual symptoms, nor in those who did., Conclusion: Worsening of visual complaints can occur in a noteworthy number of cCSC patients in the first week after half-dose verteporfin PDT. Despite the fact that no significant short-term changes on both optical coherence tomography and microperimetry have been detected in this study, the assessment could be of importance for the long-term outcome of treatment and needs further investigation.

Purpose: To identify characteristics of Caucasian chronic central serous chorioretinopathy (cCSC) patients without a complete resolution of subretinal fluid (SRF) after reduced-settings photodynamic therapy (PDT), or with a recurrence of SRF after PDT., Methods: Chronic CSC patients treated with reduced-settings PDT were divided into a successful PDT group and unsuccessful PDT group. Patients in the successful PDT group did not have any subretinal fluid (SRF) during follow-up after PDT, whereas the unsuccessful PDT group was categorized based on either persistence or recurrence of SRF after PDT treatment. Data on age, sex, best-corrected visual acuity (BCVA), PDT spot size, characteristics on fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT) were obtained., Results: Twenty-six patients in the successful PDT group (20 males, 6 females) had a mean age of 51 years (range, 25-78). In the unsuccessful PDT group, 20 males with a mean age of 60 years (range, 34-78) were included. At last visit before PDT, age, percentage of males, and percentage of patients with diffuse leakage > 1 optic disc diameter on FA were higher in the unsuccessful PDT group (p = 0.010, p = 0.029, and p = 0.008, respectively). At last visit before PDT, BCVA and the percentage of patients with intense hyperfluorescence on ICGA were lower in the unsuccessful group (p = 0.017 and p = 0.004, respectively). Patients with intense hyperfluorescence on ICGA were more likely (95% CI 1.3-333 times) to have a successful outcome (p = 0.045). A decrease in SFCT at final visit was observed in both groups (- 111 μm and p = 0.013, and - 141 μm and p = 0.007, respectively). BCVA only improved at final visit in the successful PDT group (5 Early Treatment of Diabetic Retinopathy Study letters, p < 0.001)., Conclusions: Chronic CSC patients with recurrent or persistent SRF after PDT are characterized by a higher percentage of males, more patients with diffuse leakage on FA, more patients without intense hyperfluorescence on ICGA, higher age, and lower pre-PDT and long-term BCVA than in the successful PDT group. A reduction in SFCT after PDT does not necessarily lead to complete resolution of SRF, while a resolution of SRF appears to be required to lead to a significant BCVA improvement in cCSC.

Purpose: To assess the efficacy of photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (cCSC), in whom subretinal fluid (SRF) was solely present outside the foveal area., Methods: In this retrospective study, 16 eyes of 15 cCSC patients who received half-dose PDT because of notable subjective visual complaints due to the presence of extrafoveal SRF, were included. An ophthalmic examination was performed before treatment, including Early Treatment Diabetic Retinopathy Study best-corrected visual acuity measurement, applanation tonometry, slit-lamp examination, and indirect ophthalmoscopy, followed by multimodal imaging, including fundus photography, fundus autofluorescence, spectral-domain optical coherence tomography (OCT), enhanced-depth imaging OCT of the choroid, fluorescein angiography, and indocyanine green angiography., Results: In 7 treated patients (47%), PDT led to a decrease in visual complaints at the first evaluation visit. At this visit, extrafoveal SRF on OCT had resolved in 14 eyes (88%), whereas a complete resolution of extrafoveal SRF had occurred in all eyes at final follow-up visit. At baseline, posterior cystoid retinal degeneration was also present in 5 eyes (31%) and this remained present at all evaluation visits in these patients. Choroidal thickness decreased statistically significantly in the treated eyes, both foveally and at the location of the maximum height of extrafoveal SRF. No complications of PDT were observed., Conclusions: Half-dose PDT treatment of cCSC patients with visual complaints due to extrafoveal SRF accumulation is a safe procedure leading to complete SRF resolution, a decrease in choroidal thickness, and a reduction in visual symptoms.

Background: Chronic central serous chorioretinopathy (cCSC) is an eye disease characterized by an accumulation of serous fluid under the retina. It is postulated that this fluid accumulation results from hyperpermeability and swelling of the choroid, the underlying vascular tissue of the eye, causing a dysfunction of the retinal pigment epithelium. This fluid accumulation causes neuroretinal detachment. A prolonged neuroretinal detachment in the macula can lead to permanent vision loss. Therefore, treatment is aimed primarily at achieving resolution of subretinal fluid, preferably within the first 4 months after diagnosis of the disease. A broad spectrum of treatment modalities has been investigated in cCSC, but no consensus exists on the optimal treatment of cCSC. Currently, photodynamic therapy (PDT) and high-density subthreshold micropulse laser treatment (HSML) are among the most frequently cited treatments in obtaining successful neuroretinal reattachment., Methods/design: This is a randomized, controlled, open-label, multicenter trial comparing the efficacy of half-dose PDT to HSML in treating patients with cCSC. A total of 156 patients will be recruited, 78 patients in each treatment arm, with a maximum follow-up duration of 8 months after the first treatment. A complete ophthalmological examination with vision-related quality of life (NEI VFQ-25) and stress questionnaires, will be performed at baseline, 6 to 8 weeks after the first treatment, 6 to 8 weeks after a second treatment (if necessary), and at the final follow-up visit at 7 to 8 months after the first treatment. Treatment visits will be scheduled within 3 weeks after the baseline visit, and within 3 weeks after the first control visit, if a second treatment is required., Discussion: Both half-dose PDT and HSML may be effective treatments in cCSC, but because of the lack of prospective randomized controlled trials, which treatment should be the first choice remains unclear. The aim of this study is to compare the efficacy of half-dose PDT to HSML. The primary endpoint to evaluate efficacy will be a complete absence of subretinal fluid on optical coherence tomography after treatment. Secondary functional endpoints include change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity, retinal sensitivity on microperimetry, and NEI VFQ-25 questionnaire of visual functioning. Registration number Institutional Review Board (CMO Arnhem-Nijmegen, the Netherlands): 2013/203 NL nr.: 41266.091.13 TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01797861 . Date of registration: 21 February 2013.