Author: Miguel Leitão (Portugal)
Co-authors: Miguel Leitão, Catarina Rodrigues, Rita Pinto, Vanda Nogueira
Chronic Central Serous Choroidoretinopathy (cCSC) may course with permanent visual impairment due to persistent subretinal fluid, prolonged RPE detachment and damage to photoreceptors. PDT with verteporfin, either full dose or half dose, although commonly used, may cause choriocapillaris hypoperfusion, transient upregulation of VEGF and inflammatory mediators and RPE damage. Anti-VEGF agents (mainly bevacizumab) have been used to reduce choroidal hyperpemeability in cCSC, with studies showing conflicting results regarding reduction in Central Macular Thickness (CMT) and Best Corrected Visual Acuity (BCVA) improvement. In this study we describe three cases of cCSC with bilateral, exuberant and persistent subretinal and intraretinal fluid, previously treated with eplerenone and Photodynamic Therapy (PDT) with verteporfin, without evidence of neovascularization on fluorescein angiography (FA), indocyanine green angiography (ICGA) and/or OCT. All patients had limited anatomical and functional response to a treat and extend regimen of bevacizumab and were switched to aflibercept with remarkable and sustained anatomical response though very dependent on monthly injections. These results support the notion that anti-VEGF agents and especially aflibercept may have an important role in cCSC unresponsive to conventional therapy, through their action on choroidal hyperpermeability.
Single-center retrospective cohort at Instituto de Oftalmologia Dr. Gama Pinto in Lisbon, Portugal.
Retrospective study of three cases referred to our Retina Department with progressive decrease of visual acuity bilaterally for more than 1 year, with a previous diagnosis of cCSC unresponsive to PDT and eplerenone. All patients denied prior or current use of corticosteroids and had no relevant ophthalmic history. At presentation, BCVA for the right eye (RE) and left eye (LE) were, respectively: 10/100 and 10/40 for Patient 1, less than 5/200 and 5/80 for Patient 2 and less than 5/200 and 5/80 for Patient 3. Colour fundus images showed macular atrophy, pigment alterations and serous macular detachment. On OCT, all patients had extensive retinal pigment epithelial (RPE) atrophy, increased diameter of Haller layer vessels with decrease of Sattler layer thickness and exuberant subretinal and intraretinal fluid. In addition, in the RE of the Patient 3, OCT showed an extensive macular hyperreflective subretinal lesion with well defined borders associated outer retinal tubulation, consistent with disciform scarring. FA showed a diffuse mottled pattern of leakage from the macular area in the absence of focal leaking or enhancing structures. ICGA revealed increased diameter of the choroidal vessels, without choroidal neovascularization or polyps. In addition, patients underwent blood workup and imaging to exclude hypercortisolism.
All patients were initiated on a treat and extend regimen with bevacizumab, and all three cases started with their best-seeing eye after considering visual prognosis with treatment. There was no significant improvement in vision and only partial decrease of subretinal and intraretinal fluid with bevacizumab. Patients were then switched to aflibercept with remarkable absorption of subretinal and intraretinal fluid and stabilization or modest increase in BCVA – for instance, there was an improvement from 5/80 to 5/63 of BCVA in Patient 2 after two years of treatment. Sustained response was highly dependent on monthly aflibercept injections, with exuberant recurrence of subretinal and intraretinal fluid with more than 4-6 weeks of injection interval.
The remarkable and sustained anatomic response in cCSC with monthly injections of anti-VEGF cannot be attributed to pachychoroid neovasculopathy or polypoidal vasculopathy in these cases, as these complications, as well as alternative diagnoses such as posterior uveitis with diffuse capillary leakage, were excluded with FA and ICGA. The significant anatomical and more modest functional responses in this case series, as well as their dependance on continued injections, support the hypothesis that choroidal vascular hyperpermeability is a major and persistent factor in CSC and that it can successfully be mitigated through inhibition of VEGF, which acts as a hypepermeability factor through induction of vascular fenestration and microvascular permeability. The larger response obtained after switching to aflibercept further supports this notion, since aflibercept has a superior binding affinity to VEGF, and inhibits both VEGF-A and VEGF-B and PIGF, whereas bevacizumab only inhibits VEGF-A. Improvement in vision in this series was modest; however this can be attributed to subfoveal photoreceptor damage already caused by chronicity of subretinal and intraretinal fluid before treatment with anti-VEGF was initiated. Our findings suggest a role for a prolonged treat and extend regimen of anti-VEGF for cCSC unresponsive to conventional treatment, even in the absence of neovascularization.