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Atypical transient subretinal exudation following photodynamic therapy for chronic central serous retinopathy: a case report
CASE REPORT Atypical transient subretinal exudation following photodynamic therapy for chronic central serous retinopathy: a case report Central serous retinopathy (CSR) is a common ocular disease of young and middle-aged adults that affects men more than women. It manifests as the accumulation of central subretinal fluid (SRF) with or without the presence of retinal pigment epithelial detachment (RPED) and is often associated with reduced visual acuity (VA) or metamorphopsia.1 Most cases of idiopathic CSR resolve spontaneously; however, chronic cases in which the SRF persists longer than 3 months may require treatment.2 In cases of CSR with a focal leak, retinal laser photocoagulation may be an appropriate treatment option to accelerate the resorption of SRF and improve VA. In patients with chronic fluid and persistent visual symptoms, photodynamic therapy (PDT) has been shown to be a safe and effective therapeutic option.2–5 We report a case of chronic CSR with persistent SRF despite treatment with focal laser, observation, and subsequent half-dose verteporfin PDT. This treatment resulted in drastic acute exacerbation of macular SRF within 1 day that fortunately resolved spontaneously over the next 2 months without the need for further adjunctive treatment.
CASE REPORT A 60-year-old female with a medical history significant for polymyositis and osteoporosis presented with decreased vision in her right eye. She had been followed for 2 years with asymptomatic retinal pigment epithelium (RPE) changes in her right eye, presumably from a prior episode of CSR that went undetected. She did not report any significant family history or ocular history. She had used oral prednisone in the past for polymyositis but had discontinued it for at least 2 years before her presentation. Her current medications included Azathioprine, Alendronate, Esomeprazole, Tolterodine, and vitamins B and D. On examination, her best-corrected visual acuity (BCVA) was 20/50 OD and 20/40 OS. Macular examination of her right eye demonstrated central RPE changes,
SRF, and no RPED. Her contralateral eye showed mild RPE mottling with no SRF. Optical coherence tomography (OCT) confirmed SRF and intraretinal photoreceptor precipitates consistent with a diagnosis of CSR in the right eye, and normal macular contour in the left eye (Fig. 1). After persistent SRF after a 2-month period of observation, the patient elected to pursue treatment options. An intravenous fluorescein angiogram demonstrated a moderately sized focal leak superior to the fovea in the right eye (Fig. 2). Focal thermal laser was directly applied to this area. At 1-month postlaser follow-up, the patient still complained of blurred vision, and OCT showed decreased but persistent SRF (Fig. 3). This persisted at the 4-month follow-up and VA remained at 20/50 OD. An indocyanine green angiogram demonstrated a central engorged choroidal vessel (early frame) and central choroidal hyperpermeability (late frame) in the right eye (Fig. 2). ICGguided PDT was offered and carried out uneventfully using half-dose verteporfin and full-fluence laser (50 J/ cm2) with a 6-mm spot size and total energy of 160 mJ. One day post-PDT, the patient returned with significant vision loss in the treated right eye with BCVA of 20/ 80 and a massive increase in subfoveal SRF demonstrated on OCT (Fig. 4). Her vision further deteriorated the following day to 20/100, and OCT scan demonstrated a further increase in her SRF with a central retinal thickness 689 μm. On clinical examination there was no evidence of subretinal haemorrhage, lipid, or choroidal neovascular membrane. One week later, there was a significant decrease in SRF (Fig. 4), and at 1-month follow-up, most of the SRF had resolved spontaneously (Fig. 5). At 2 months there was complete resolution of SRF, and her BCVA returned to 20/40.
DISCUSSION Most cases of CSR resolve spontaneously and do not require treatment.2 Approximately 10%–20% of cases that demonstrate SRF persisting longer than 3 months are labeled as chronic CSR. Various treatment options have been described for these patients, including focal thermal
Fig. 1 — Optical coherence tomography (OCT) of right and left eyes baseline. OCT comparing the right eye (left image) to the left eye (right image) at baseline measurements. CAN J OPHTHALMOL — VOL. ], NO. ], ] 2016
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Fig. 2 — IVFA of right and left eyes as well as indocyanine green angiogram (ICGA) of the right eye. IVFA comparing the right eye (top left) to the left eye (top right). Note the moderately sized focal leak superior to the fovea in the right eye. An early frame ICGA of the right eye (bottom left) demonstrated an engorged choroidal vessel, and the late-frame ICGA (bottom right) demonstrated choroidal hyperpermeability.
Fig. 3 — Post-thermal laser treatment optical coherence tomography of the right eye. One-month follow-up postlaser (left) compared with 4-month follow-up postlaser (right).
Fig. 4 — Immediate optical coherence tomography (OCT) post–photodynamic therapy (post-PDT) of the right eye. Two days post-PDT (left), 3 days post-PDT (centre), and 1-week post-PDT (right) OCT.
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Fig. 5 — Optical coherence tomography (OCT) 1 and 2 months post–photodynamic therapy (post-PDT). One-month follow-up post-PDT of the right eye only (top). Two-month follow-up post-PDT demonstrating complete resolution of subretinal fluid comparing the right (bottom left) and left (bottom right) eyes.
laser photocoagulation, finasteride, and PDT. Although focal thermal laser is a common first-line approach to active CSR, PDT has been a well-described treatment strategy in both acute and chronic CSR. PDT dosing protocols for CSR were initially based on the Verteporfin in photodynamic therapy study (VIP)6 and treatment of AMD with photodynamic therapy study (TAP)7 studies using standard dose verteporfin (6 mg/m2) and standard fluence (50 J/cm2). Although there have been rare reports of acute vision loss using PDT in the AMD population,8 there have been no such reports in the CSR population. In an effort to further reduce possible PDT complications, various modified verteporfin dosing protocols have been recently described for CSR. These protocols include half-dose verteporfin,3,9 half-fluence PDT,5,10 one-third dose verteporfin,11 minimal-fluence PDT,12 and a combination of half-dose verteporfin with half-fluence PDT.13 Both the half-dose verteporfin and half-fluence PDT studies have demonstrated equivalent efficacy, safety, and long-term results with a trend toward faster resolution of anatomic and functional changes in the half-dose verteporfin group.4 Lai et al. recently reported that long-term outcomes of half-dose verteporfin PDT in the chronic CSR group were generally well tolerated.2 However, this article does report some uncommon complications during the 36-month follow-up period, which included RPE atrophy, PCV, macular scar, epiretinal membranes, and choroidal neovascular membrane (CNVM).2 There have been no case reports in the CSR population of acute exacerbation of SRF after PDT using any dose of verteporfin, and especially in the half-dose verteporfin PDT group. However, there have been case reports of
significant subretinal exudation after standard-dose verteporfin with full-fluence PDT in AMD patients.14,15 Although the mechanism has not been clearly delineated, it is hypothesized that the increased transudate is attributable to the breakdown of the vascular blood retinal barrier and/or a dysfunction of the RPE pump with or without choroidal nonperfusion. The changes seen in our case of predominantly SRF, the absence of intraretinal fluid, and the transient nature, with return of both functional vision and anatomic features back to baseline, suggest a temporary dysfunction of the RPE pump as a primary mechanism. However, consideration to repeating angiography to diagnose choroidal ischemia would be warranted if vision loss was persistent. In conclusion, acute subretinal exudation is a rare occurrence after half-dose verteporfin PDT in chronic CSR. It is important to be aware that observation may be an appropriate treatment strategy in this transient complication without compromising functional or anatomical outcomes.
The authors have no proprietary or commercial interest in any materials discussed in this article.
Disclosure:
Ahmad Al-Awadi, BSc,* Efrem D. Mandelcorn, MD, FRCSC,†,‡ Sohel Somani, MD, FRCSC†,‡ *
Wayne State University School of Medicine, Detroit, Mich; Department of Ophthalmology and Vision Sciences, University of Toronto, University Health Network, Toronto, Ont; ‡William Osler Health System, Brampton, Ont.
†
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2016
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Case Report Correspondence to: Sohel Somani, MD, FRCSC: [email protected] REFERENCES 1. Gass JDM. Pathogenesis of disciform detachment of the neuroepithelium. II. Idiopathic central serous choroidopathy. Am J Ophthalmol. 1967;63:587-615. 2. Lai TY, Wong RL, Chan WM. Long-term outcome of half-dose verteporfin photodynamic therapy for the treatment of central serous chorioretinopathy (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2015;113:T81-827. 3. Chan WM, Lai TY, Lai RY, Tang EW, Liu DT, Lam DS. Safety enhanced photodynamic therapy for chronic central serous chorioretinopathy: one-year results of a prospective study. Retina. 2008;28:85-93. 4. Nicolo M, Eandi CM, Alovisi C, et al. Half-fluence versus half-dose photodynamic therapy in chronic central serous chorioretinopathy. Am J Ophthalmol. 2014;157:1033-7. 5. Shin JY, Woo SJ, Yu HG, Park KH. Comparison of efficacy and safety between half-fluence and full-fluence photodynamic therapy for chronic central serous chorioretinopathy. Retina. 2011;31:119-26. 6. Verteporfin in Photodynamic Therapy Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. 1-year results of a randomized clinical trial—VIP report no. 1. Ophthalmology. 2001;108:841-52. 7. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP report. Arch Ophthalmol. 1999; 117:1329-45.
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8. Recchia FM, Greenbaum S, Recchia CA, Ruby AJ, Alldredge CD, Hassan TS. Self-reported acute decrease in visual acuity after photodynamic therapy for age-related macular degeneration. Retina. 2006;26:1042-8. 9. Lai TY, Chan WM, Li H, Lai RY, Liu DT, Lam DS. Safety enhanced photodynamic therapy with half dose verteporfin for chronic central serous chorioretinopathy: a short term pilot study. Br J Ophthalmol. 2006;90:869-74. 10. Reibaldi M, Cardascia N, Longo A, et al. Standard-fluence versus low-fluence photodynamic therapy in chronic central serous chorioretinopathy: a nonrandomized clinical trial. Am J Ophthalmol. 2010;149:307-15. e302 . 11. Uetani R, Ito Y, Oiwa K, Ishikawa K, Terasaki H. Half-dose vs onethird-dose photodynamic therapy for chronic central serous chorioretinopathy. Eye. 2012;26:640-9. 12. Butler AL, Fung AT, Merkur AB, Albiani DA, Forooghian F. Very minimal fluence photodynamic therapy for chronic central serous chorioretinopathy. Can J Ophthalmol. 2012;47:42-4. 13. Liu CF, Chen LJ, Tsai SH, et al. Half-dose verteporfin combined with half-fluence photodynamic therapy for chronic central serous chorioretinopathy. J Ocul Pharm Ther. 2014;30:400-5. 14. Holz ER, Linares L, Mieler WF, Weinberg DV. Exudative complications after photodynamic therapy. Arch Ophthalmol. 2003;121:1649-52. 15. Jalil A, Mercieca K, Chaudhry NL, Stanga PE. Choroidal nonperfusion with significant subretinal exudation after PDT of predominantly classic CNV: an OCT and FFA study. Eur J Ophthalmol. 2009;19:490-3. Can J Ophthalmol 2016;]:]]]–]]] 0008-4182/16/$-see front matter & 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2016.08.001
CASE REPORT A 60-year-old female with a medical history significant for polymyositis and osteoporosis presented with decreased vision in her right eye. She had been followed for 2 years with asymptomatic retinal pigment epithelium (RPE) changes in her right eye, presumably from a prior episode of CSR that went undetected. She did not report any significant family history or ocular history. She had used oral prednisone in the past for polymyositis but had discontinued it for at least 2 years before her presentation. Her current medications included Azathioprine, Alendronate, Esomeprazole, Tolterodine, and vitamins B and D. On examination, her best-corrected visual acuity (BCVA) was 20/50 OD and 20/40 OS. Macular examination of her right eye demonstrated central RPE changes,
SRF, and no RPED. Her contralateral eye showed mild RPE mottling with no SRF. Optical coherence tomography (OCT) confirmed SRF and intraretinal photoreceptor precipitates consistent with a diagnosis of CSR in the right eye, and normal macular contour in the left eye (Fig. 1). After persistent SRF after a 2-month period of observation, the patient elected to pursue treatment options. An intravenous fluorescein angiogram demonstrated a moderately sized focal leak superior to the fovea in the right eye (Fig. 2). Focal thermal laser was directly applied to this area. At 1-month postlaser follow-up, the patient still complained of blurred vision, and OCT showed decreased but persistent SRF (Fig. 3). This persisted at the 4-month follow-up and VA remained at 20/50 OD. An indocyanine green angiogram demonstrated a central engorged choroidal vessel (early frame) and central choroidal hyperpermeability (late frame) in the right eye (Fig. 2). ICGguided PDT was offered and carried out uneventfully using half-dose verteporfin and full-fluence laser (50 J/ cm2) with a 6-mm spot size and total energy of 160 mJ. One day post-PDT, the patient returned with significant vision loss in the treated right eye with BCVA of 20/ 80 and a massive increase in subfoveal SRF demonstrated on OCT (Fig. 4). Her vision further deteriorated the following day to 20/100, and OCT scan demonstrated a further increase in her SRF with a central retinal thickness 689 μm. On clinical examination there was no evidence of subretinal haemorrhage, lipid, or choroidal neovascular membrane. One week later, there was a significant decrease in SRF (Fig. 4), and at 1-month follow-up, most of the SRF had resolved spontaneously (Fig. 5). At 2 months there was complete resolution of SRF, and her BCVA returned to 20/40.
DISCUSSION Most cases of CSR resolve spontaneously and do not require treatment.2 Approximately 10%–20% of cases that demonstrate SRF persisting longer than 3 months are labeled as chronic CSR. Various treatment options have been described for these patients, including focal thermal
Fig. 1 — Optical coherence tomography (OCT) of right and left eyes baseline. OCT comparing the right eye (left image) to the left eye (right image) at baseline measurements. CAN J OPHTHALMOL — VOL. ], NO. ], ] 2016
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Case Report
Fig. 2 — IVFA of right and left eyes as well as indocyanine green angiogram (ICGA) of the right eye. IVFA comparing the right eye (top left) to the left eye (top right). Note the moderately sized focal leak superior to the fovea in the right eye. An early frame ICGA of the right eye (bottom left) demonstrated an engorged choroidal vessel, and the late-frame ICGA (bottom right) demonstrated choroidal hyperpermeability.
Fig. 3 — Post-thermal laser treatment optical coherence tomography of the right eye. One-month follow-up postlaser (left) compared with 4-month follow-up postlaser (right).
Fig. 4 — Immediate optical coherence tomography (OCT) post–photodynamic therapy (post-PDT) of the right eye. Two days post-PDT (left), 3 days post-PDT (centre), and 1-week post-PDT (right) OCT.
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Fig. 5 — Optical coherence tomography (OCT) 1 and 2 months post–photodynamic therapy (post-PDT). One-month follow-up post-PDT of the right eye only (top). Two-month follow-up post-PDT demonstrating complete resolution of subretinal fluid comparing the right (bottom left) and left (bottom right) eyes.
laser photocoagulation, finasteride, and PDT. Although focal thermal laser is a common first-line approach to active CSR, PDT has been a well-described treatment strategy in both acute and chronic CSR. PDT dosing protocols for CSR were initially based on the Verteporfin in photodynamic therapy study (VIP)6 and treatment of AMD with photodynamic therapy study (TAP)7 studies using standard dose verteporfin (6 mg/m2) and standard fluence (50 J/cm2). Although there have been rare reports of acute vision loss using PDT in the AMD population,8 there have been no such reports in the CSR population. In an effort to further reduce possible PDT complications, various modified verteporfin dosing protocols have been recently described for CSR. These protocols include half-dose verteporfin,3,9 half-fluence PDT,5,10 one-third dose verteporfin,11 minimal-fluence PDT,12 and a combination of half-dose verteporfin with half-fluence PDT.13 Both the half-dose verteporfin and half-fluence PDT studies have demonstrated equivalent efficacy, safety, and long-term results with a trend toward faster resolution of anatomic and functional changes in the half-dose verteporfin group.4 Lai et al. recently reported that long-term outcomes of half-dose verteporfin PDT in the chronic CSR group were generally well tolerated.2 However, this article does report some uncommon complications during the 36-month follow-up period, which included RPE atrophy, PCV, macular scar, epiretinal membranes, and choroidal neovascular membrane (CNVM).2 There have been no case reports in the CSR population of acute exacerbation of SRF after PDT using any dose of verteporfin, and especially in the half-dose verteporfin PDT group. However, there have been case reports of
significant subretinal exudation after standard-dose verteporfin with full-fluence PDT in AMD patients.14,15 Although the mechanism has not been clearly delineated, it is hypothesized that the increased transudate is attributable to the breakdown of the vascular blood retinal barrier and/or a dysfunction of the RPE pump with or without choroidal nonperfusion. The changes seen in our case of predominantly SRF, the absence of intraretinal fluid, and the transient nature, with return of both functional vision and anatomic features back to baseline, suggest a temporary dysfunction of the RPE pump as a primary mechanism. However, consideration to repeating angiography to diagnose choroidal ischemia would be warranted if vision loss was persistent. In conclusion, acute subretinal exudation is a rare occurrence after half-dose verteporfin PDT in chronic CSR. It is important to be aware that observation may be an appropriate treatment strategy in this transient complication without compromising functional or anatomical outcomes.
The authors have no proprietary or commercial interest in any materials discussed in this article.
Disclosure:
Ahmad Al-Awadi, BSc,* Efrem D. Mandelcorn, MD, FRCSC,†,‡ Sohel Somani, MD, FRCSC†,‡ *
Wayne State University School of Medicine, Detroit, Mich; Department of Ophthalmology and Vision Sciences, University of Toronto, University Health Network, Toronto, Ont; ‡William Osler Health System, Brampton, Ont.
†
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2016
3
Case Report Correspondence to: Sohel Somani, MD, FRCSC: [email protected] REFERENCES 1. Gass JDM. Pathogenesis of disciform detachment of the neuroepithelium. II. Idiopathic central serous choroidopathy. Am J Ophthalmol. 1967;63:587-615. 2. Lai TY, Wong RL, Chan WM. Long-term outcome of half-dose verteporfin photodynamic therapy for the treatment of central serous chorioretinopathy (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2015;113:T81-827. 3. Chan WM, Lai TY, Lai RY, Tang EW, Liu DT, Lam DS. Safety enhanced photodynamic therapy for chronic central serous chorioretinopathy: one-year results of a prospective study. Retina. 2008;28:85-93. 4. Nicolo M, Eandi CM, Alovisi C, et al. Half-fluence versus half-dose photodynamic therapy in chronic central serous chorioretinopathy. Am J Ophthalmol. 2014;157:1033-7. 5. Shin JY, Woo SJ, Yu HG, Park KH. Comparison of efficacy and safety between half-fluence and full-fluence photodynamic therapy for chronic central serous chorioretinopathy. Retina. 2011;31:119-26. 6. Verteporfin in Photodynamic Therapy Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. 1-year results of a randomized clinical trial—VIP report no. 1. Ophthalmology. 2001;108:841-52. 7. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP report. Arch Ophthalmol. 1999; 117:1329-45.
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8. Recchia FM, Greenbaum S, Recchia CA, Ruby AJ, Alldredge CD, Hassan TS. Self-reported acute decrease in visual acuity after photodynamic therapy for age-related macular degeneration. Retina. 2006;26:1042-8. 9. Lai TY, Chan WM, Li H, Lai RY, Liu DT, Lam DS. Safety enhanced photodynamic therapy with half dose verteporfin for chronic central serous chorioretinopathy: a short term pilot study. Br J Ophthalmol. 2006;90:869-74. 10. Reibaldi M, Cardascia N, Longo A, et al. Standard-fluence versus low-fluence photodynamic therapy in chronic central serous chorioretinopathy: a nonrandomized clinical trial. Am J Ophthalmol. 2010;149:307-15. e302 . 11. Uetani R, Ito Y, Oiwa K, Ishikawa K, Terasaki H. Half-dose vs onethird-dose photodynamic therapy for chronic central serous chorioretinopathy. Eye. 2012;26:640-9. 12. Butler AL, Fung AT, Merkur AB, Albiani DA, Forooghian F. Very minimal fluence photodynamic therapy for chronic central serous chorioretinopathy. Can J Ophthalmol. 2012;47:42-4. 13. Liu CF, Chen LJ, Tsai SH, et al. Half-dose verteporfin combined with half-fluence photodynamic therapy for chronic central serous chorioretinopathy. J Ocul Pharm Ther. 2014;30:400-5. 14. Holz ER, Linares L, Mieler WF, Weinberg DV. Exudative complications after photodynamic therapy. Arch Ophthalmol. 2003;121:1649-52. 15. Jalil A, Mercieca K, Chaudhry NL, Stanga PE. Choroidal nonperfusion with significant subretinal exudation after PDT of predominantly classic CNV: an OCT and FFA study. Eur J Ophthalmol. 2009;19:490-3. Can J Ophthalmol 2016;]:]]]–]]] 0008-4182/16/$-see front matter & 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2016.08.001