Alexandre Matet

Central serous chorioretinopathy: Recent findings and new physiopathology hypothesis

Central serous chorioretinopathy (CSCR) is a major cause of vision threat among middle-aged male individuals. Multimodal imaging led to the description of a wide range of CSCR manifestations, and highlighted the contribution of the choroid and pigment epithelium in CSCR pathogenesis. However, the exact molecular mechanisms of CSCR have remained uncertain. The aim of this review is to recapitulate the clinical understanding of CSCR, with an emphasis on the most recent findings on epidemiology, risk factors, clinical and imaging diagnosis, and treatments options. It also gives an overview of the novel mineralocorticoid pathway hypothesis, from animal data to clinical evidences of the biological efficacy of oral mineralocorticoid antagonists in acute and chronic CSCR patients. In rodents, activation of the mineralocorticoid pathway in ocular cells either by intravitreous injection of its specific ligand, aldosterone, or by over-expression of the receptor specifically in the vascular endothelium, induced ocular phenotypes carrying many features of acute CSCR. Molecular mechanisms include expression of the calcium-dependent potassium channel (KCa2.3) in the endothelium of choroidal vessels, inducing subsequent vasodilation. Inappropriate or over-activation of the mineralocorticoid receptor in ocular cells and other tissues (such as brain, vessels) could link CSCR with the known co-morbidities observed in CSCR patients, including hypertension, coronary disease and psychological stress.

Resolution of foveal detachment in dome-shaped macula after treatment by spironolactone: report of two cases and mini-review of the literature.

Dome-shaped macula (DSM) was recently described in myopic patients as a convex protrusion of the macula within a posterior pole staphyloma. The pathogenesis of DSM and the development of associated serous foveal detachment (SFD) remain unclear. The obstruction of choroidal outflow and compressive changes of choroidal capillaries have been proposed as causative factors. In this paper, we report two cases of patients with chronic SFD associated with DSM treated with oral spironolactone. After treatment, there was a complete resolution of SFD in both patients. To the best of our knowledge, this is the first report of successful treatment of SFD in DSM by a mineralocorticoid receptor antagonist.

VOLUME-RENDERED ANGIOGRAPHIC AND STRUCTURAL OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF MACULAR TELANGIECTASIA TYPE 2.

Purpose: To evaluate multimodal imaging including volume-rendered angiographic and structural optical coherence tomography of macular telangiectasia Type 2 (MacTel2) for right-angle vein complexes, macular cavitations, and signs of deeper retinal vascular invasion. Methods: Retrospective review of imaging performed in a community-based retinal referral center. The eyes were scanned using optical coherence tomography using split-spectrum amplitude-decorrelation techniques to derive flow information. These data were extracted and used to create volume-rendered images of the retinal vasculature with integrated structural information derived from the component optical coherence tomographic images. Results: There were 24 eyes of 16 patients who had a mean age of 61.8 years. Right-angle veins seemed in association with vascular proliferation external to the deep vascular plexus. The origin of a right-angle vein was surrounded by a stellate arrangement of radiating retinal vessels apparently caused by contraction of surrounding tissue in the temporal macula. Cavitations were found in the fovea and varied in size and configuration from one examination to the next. Many smaller cavitations, called microcavitations, were seen in the surrounding macula. Vascular invasion occurred into the subretinal space. Conclusion: There are contractile features of the tissue in the temporal macula and the number, size, and temporal variations in the cavitations have not been in not mentioned in previous published descriptions of MacTel2. Vascular invasion of deeper layers occurred in the temporal macula through the outer nuclear layer. Volume-rendered angiographic and structural optical coherence tomography offers unprecedented ability to examine the vascular interrelationships their associations with cavitations in the macula.

Acute Central Serous Chorioretinopathy: Factors Influencing Episode Duration

Purpose: To evaluate the influence of clinical and multimodal imaging parameters on the duration of acute central serous chorioretinopathy (CSCR) episodes. Methods: Consecutive patients with first, treatment-naïve central serous chorioretinopathy episodes presenting within 20 days of symptoms onset were prospectively included. They were reevaluated 15 days to 20 days later, followed by monthly evaluation for 6 months. Subfoveal choroidal thickness (SFCT), fluorescein leakage intensity on fluorescein angiography, elevation of retinal pigment epithelium (RPE) lesions at leakage sites, focal/multifocal pattern of indocyanine green angiography (ICGA) at baseline, time-dependent pattern of subretinal fluid (SRF) resorption on OCT using volume segmentation, history of corticosteroid intake and mean blood pressure were evaluated using univariate (Log rank test) and multivariate (Cox proportional hazard regression) survival analysis. Results: Thirty-one patients were included (26 men, 5 women, mean age: 40.0 ± 8.9 years, range: 24–58), of which 26 (84%) had episode resolution by 6 months. Using univariate analysis, episode duration was longer in cases with subfoveal choroidal thickness ≥500 &mgr;m (P = 0.0002), retinal pigment epithelium elevation at leakage sites ≥50 &mgr;m (P = 0.033), and a peak in subretinal fluid observed during follow-up (P = 0.013), and there was a near-significant association of intense fluorescein leakage (P = 0.074) with longer episodes. Using multivariate analysis, subfoveal choroidal thickness ≥500 &mgr;m (P = 0.017), retinal pigment epithelium elevation at leakage sites ≥50 &mgr;m (P = 0.010) and patient age ≥40 years (P = 0.010) were significantly and independently associated to longer episodes. Indocyanine green angiography pattern, corticosteroid intake, and blood pressure did not influence episode duration. Conclusion: Older age, higher subfoveal choroidal thickness, and higher degree of retinal pigment epithelium alteration at leakage sites are independent factors of longer acute central serous chorioretinopathy episodes.

Sustained-Release Steroids for the Treatment of Diabetic Macular Edema

Glucocorticoids have been used for decades in the treatment of ocular disorders via topical, periocular, and more recently intravitreal routes. However, their exact mechanisms of action on ocular tissues remain imperfectly understood. Fortunately, two recently approved intravitreal sustained-release drug delivery systems have opened new perspectives for these very potent drugs. To date, among other retinal conditions, their label includes diabetic macular edema, for which a long-lasting therapeutic effect has been demonstrated both morphologically and functionally in several randomized clinical trials. The rate of ocular complications of intravitreal sustained-release steroids, mainly cataract formation and intraocular pressure elevation, is higher than with anti-vascular endothelial growth factor agents. Yet, a better understanding of the mechanisms underlying these adverse effects and the search for the minimal efficient dose should help optimize their therapeutic window.

RISK FACTORS FOR RECURRENCES OF CENTRAL SEROUS CHORIORETINOPATHY

Purpose: To describe recurrence patterns and investigate candidate risk factors for recurrences of central serous chorioretinopathy. Methods: In 46 patients with acute central serous chorioretinopathy and follow-up >12 months after first episode resolution, parameters influencing recurrences were retrospectively evaluated using a frailty Cox proportional hazard survival model. Covariates included baseline systemic findings: age, gender, corticosteroid use, stress, shift work, sleep disorder, depression, allergy, cardiovascular risk; baseline optical coherence tomography findings: subfoveal choroidal thickness, pigment epithelial detachment pattern (regular/bump/irregular), number of subretinal hyperreflective foci at leakage site; baseline angiographic findings: fluorescein leakage intensity (intense/moderate/subtle/absent), hyperpermeability pattern on indocyanine-green angiography (focal/multifocal); and episode-related findings: duration and treatment of previous episode. Results: Twenty of 46 subjects (43%) presented ≥1 recurrences during a mean follow-up of 29.9 ± 9.5 months (range, 15–54 months). Follow-up duration did not differ between cases with or without recurrences (P = 0.3). Worse final visual acuity levels (logarithm of the minimal angle of resolution) were associated with a higher number of episodes during follow-up (P = 0.032, r = 0.28). In a univariate analysis, higher subfoveal choroidal thickness (P = 0.021), nonintense fluorescein leakage (= moderate/subtle/absent, P = 0.033), multiple subretinal hyperreflective foci (P = 0.026), and shift work (P < 0.0001) were significantly associated with recurrences, with a near-significant influence of irregular pigment epithelial detachment (P = 0.093). In a multivariate analysis, higher subfoveal choroidal thickness (P = 0.007), nonintense fluorescein leakage (P = 0.003) and shift work (P < 0.0001) remained significant and independent risk factors for recurrences. Conclusion: Multiple factors influence the risk of central serous chorioretinopathy recurrence. These findings may contribute to identify patients at higher risk, who could benefit from earlier or more intensive treatment.

Efficacy Of Intravitreal Aflibercept In Macular Telangiectasia Type 1 Is Linked To The Ocular Angiogenic Profile

Purpose: To evaluate intravitreal aflibercept in macular telangiectasia Type 1 (MacTel 1) patients and measure their ocular angiogenic profile. Methods: Eight subjects with MacTel 1 refractory to bevacizumab, ranibizumab, or laser therapy and switched to aflibercept were included. Best-corrected visual acuity, central macular thickness, and cystic areas quantified on optical coherence tomography B-scans were assessed during 12 months. Perifoveal capillary densities were measured on optical coherence tomography angiography. Aqueous humor was sampled from six patients and eight control subjects undergoing cataract extraction. Growth factors were quantified using a multiarray immunoassay. Results: Over 12 months, patients received 6.6 ± 1.4 (range, 5–8) intravitreal aflibercept injections. Twelve months after switching to aflibercept, best-corrected visual acuity increased by ≥5 letters in 5 of 8 patients, compared with preaflibercept levels. Mean best-corrected visual acuity improved from 79.6 (∼20/50) to 88.0 (∼20/35) Early Treatment Diabetic Retinopathy Study letters (P = 0.042), and central macular thickness decreased from 434 ± 98 &mgr;m to 293 ± 59 &mgr;m (P = 0.014). Compared with control subjects, the profile of angiogenic factors in MacTel 1 eyes revealed no difference in vascular endothelial growth factor-A levels but significantly higher levels of placental growth factor (P = 0.029), soluble vascular endothelial growth factor receptor-1 (sFlt-1; P = 0.013), vascular endothelial growth factor-D (P = 0.050), and Tie-2 (P = 0.019). Placental growth factor levels inversely correlated with both superficial and deep capillary plexus densities on optical coherence tomography angiography (P = 0.03). Conclusion: The clinical response to aflibercept coupled to the angiogenic profile of MacTel 1 eyes support the implication of the placental growth factor/Flt-1 pathway in MacTel 1.

Radiation Maculopathy After Proton Beam Therapy for Uveal Melanoma: Optical Coherence Tomography Angiography Alterations Influencing Visual Acuity.

Purpose To analyze microvascular and structural changes in radiation maculopathy and their influence on visual acuity (VA), using optical coherence tomography (OCT) and OCT angiography (OCTA). Methods This was a retrospective analysis of consecutive patients with radiation maculopathy, 12 months or more after proton-beam irradiation for uveal melanoma, imaged with fluorescein angiography, OCT, and OCTA. Clinical parameters potentially affecting VA were recorded, including OCTA-derived metrics: foveal avascular zone (FAZ) area, vascular density, and local fractal dimension of the superficial (SCP) and deep capillary plexuses (DCP). Nonirradiated fellow eyes served as controls. Results Ninety-three patients were included. FAZ was larger, while SCP/DCP capillary density and local fractal dimension were lower in the 35 irradiated than in the 35 fellow eyes (P < 0.0001). Microvascular alterations graded on fluorescein angiography (minimally damaged/disrupted/disorganized) were correlated to FAZ area and SCP/DCP density on OCTA (P < 0.01). By univariate analysis, worse VA was associated to macular detachment at presentation (P = 0.024), total macular irradiation (P = 0.0008), higher central macular thickness (CMT) (P = 0.019), higher absolute CMT variation (P < 0.0001), cystoid edema (P = 0.030), ellipsoid zone disruption (P = 0.002), larger FAZ (P < 0.0001), lower SCP (P = 0.001) and DCP capillary density (P < 0.0001), and lower SCP (P = 0.009) and DCP local fractal dimension (P < 0.0001). Two multivariate models with either capillary density or fractal dimension as covariate showed that younger age (P = 0.014/0.017), ellipsoid zone disruption (P = 0.034/0.019), larger FAZ (P = 0.0006/0.002), and lower DCP density (P = 0.008) or DCP fractal dimension (P = 0.012), respectively, were associated with worse VA. Conclusions VA of eyes with radiation maculopathy is influenced by structural and microvascular factors identified with OCTA, including FAZ area and DCP integrity.

Central Serous Chorioretinopathy.

Central serous is an atypical form of macular edema with mostly accumulation of fluid under the retina. It contitutes a pure phenotype of retinal pigment epithelium barrier breakdown. Another particularity is the good visual preservation despite important fluid volume increase in the macula.

B-Scan and ‘En-Face’Spectral-Domain Optical Coherence Tomography Imaging for the Diagnosis and Follow-Up of White Dot Syndromes

The term ‘white dot syndromes’ (WDS) refers to several inflammatory diseases of the retina and choroid caused by immune dysregulation. They consist of the following disorders, with overlapping clinical features: • Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) • Serpiginous choroidopathy • Multiple evanescent white dot syndrome (MEWDS) • Birdshot retinochoroidopathy • Acute retinal pigment epitheliitis (ARPE) • Multifocal choroiditis and panuveitis syndrome (MCP) • Punctuate inner choroidopathy (PIC), and • Acute zonal occult outer retinopathy (AZOOR) These conditions usually occur following an influenza-like illness, but their patho-physiologic mechanism remains poorly understood. The white dot syndromes affect more frequently young females and individuals with mild myopia, and present as white or yellow, deep, round lesions in the central fundus. Their size and number can vary between each entity, as well as their unior bilateral involvement.