Purpose
To describe the pre-exudative stage of exudative perifoveal vascular anomalous complex (ePVAC), referred to as nonexudative PVAC (nePVAC).
Design
Retrospective noncomparative case series.
Methods
Patients diagnosed with nePVAC were identified at 4 retina referral centers worldwide. Multimodal retinal imaging, including structural optical coherence tomography (OCT) and OCT-angiography (OCT-A), were performed at baseline and follow-up visits.
Results
Six eyes (6 patients, mean 75 ± 10 years of age) were included. Unrelated chorioretinal diseases were diagnosed in the affected eyes in 5 of 6 cases. At baseline, nePVAC is characterized by microvascular abnormalities featuring an isolated, perifoveal, large intraretinal aneurysm surrounded by capillary rarefaction at OCT-A examination, without any sign of exudation with structural OCT, and without visual impairment. Four patients were followed for a mean of 21 ± 14 months. During the follow-up, 3 of 4 eyes (75%) developed signs of exudation after a mean of 15 ± 9 months, associated with metamorphopsia and visual decline at the time of exudation. Best-corrected visual acuity decreased from 20/25 to 20/40 Snellen equivalent ( P = .035) and central macular thickness increased from 268 ± 27 μm to 339 ± 65 μm ( P = .145). Three patients were treated with 2.3 ± 0.6 intravitreal injections of anti–vascular endothelial growth factor without significant improvement of best-corrected visual acuity or macular edema.
Conclusions
nePVAC may represent the subclinical pre-exudative stage of ePVAC, notable for an absence of exudation or visual impairment. nePVAC and ePVAC should be considered as part of the same spectrum, namely PVAC. Typically, nePVAC develops signs of exudation over time, causing metamorphopsia and visual decline and therefore these lesions warrant continued close monitoring with multimodal retinal imaging.
Perifoveal exudative vascular anomalous complex (PEVAC) is a relatively new entity described for the first time in 2011 by Querques and associates as a unilateral, isolated, perifoveal aneurysmal lesion surrounded by focal microvascular abnormalities. As reported by our group and others, PEVAC is a macular disease that can affect healthy patients but also patients with other coincident macular diseases, including age-related macular degeneration (AMD) and pathologic myopia. With multimodal imaging, PEVAC appears as an isolated aneurysmal lesion with detectable internal flow using optical coherence tomography angiography (OCTA). Using structural OCT, PEVAC is usually located in the retinal layers between the outer plexiform layer (OPL) and the ganglion cell complex (GCC), displaying signs of exudation. The intraretinal cystoid macular edema caused by PEVAC is usually unresponsive to intravitreal injections of anti–vascular endothelial growth factor (VEGF), , , even if a patient with PEVAC had complete resolution of the exudation after 13 intravitreal anti-VEGF injections as reported by Mrejen and associates. Thermal laser photocoagulation has been associated with better results with resolution of the intraretinal cystoid edema, but laser also has risks because of the proximity of PEVAC to the fovea. Typically, PEVAC lesions show a stable clinical course, with no significant improvement or worsening in the visual function and intraretinal cystoid macular edema during follow-up. However, in some cases, spontaneous resolution of the intraretinal edema may occur. ,
Recently, several authors have expanded our knowledge regarding the multimodal retinal imaging features of PEVAC. However, studies to detect evidence of PEVAC preceding the onset of exudation are lacking. The purpose of the present study was to describe nonexudative perifoveal vascular anomalous complex (nePVAC), which may represent a subclinical pre-exudative stage of PEVAC, characterized by focal microvascular abnormalities and an isolated aneurysmal lesion but without signs of exudation. Assuming the latter, we propose to slightly change the original acronym for the exudative lesion from PEVAC to ePVAC (exudative perifoveal vascular anomalous complex). By keeping the same pronunciation, all the spectrum is named the same, which in turn allows better categorizing of the exudative and nonexudative form of PVAC. We report on the multimodal imaging findings and the clinical progression of nePVAC.
Methods
This was a retrospective noncomparative case series comprised of 4 retina referral centers (Medical Retina and Imaging Unit of the Department of Ophthalmology of University Vita-Salute San Raffaele in Milan, Italy; Vitreous Retina Macula Consultants of New York, in New York, New York, USA; Department of Ophthalmology of University Paris Est, in Creteil, France; and the Doheny Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA). Clinical data of nePVAC cases presenting between September 2014 and September 2019 were collected. The study was conducted in accordance with the tenets set forth in the Declaration of Helsinki for research involving human subjects. All patients signed a written informed consent and respective local institutional review board or ethics committee approval was obtained by the coauthors of this study for each of all 4 involved centers.
The inclusion criteria for this study included patients ≥18 years of age with a diagnosis of nePVAC. nePVAC was defined as an isolated, perifoveal, large retinal aneurysm surrounded by microvascular abnormalities, and without any sign of exudation (ie, no evidence of intraretinal or subretinal fluid by spectral-domain OCT) at the baseline visit.
Exclusion criteria included: 1) the presence of diabetes mellitus, uncontrolled hypertension, or other systemic cardiovascular diseases; 2) the presence of any other retinal vascular diseases (eg, diabetic retinopathy, retinal vein occlusion, retinal artery occlusion, or hypertensive retinopathy); 3) presence of any inflammatory retinal diseases (ie, posterior uveitis); 4) any previous retinal treatments (eg, laser photocoagulation, photodynamic therapy, intravitreal injections of anti-VEGF or steroid); 5) presence of significant media opacities limiting the quality of multimodal imaging (eg, corneal opacity or cataract or anterior or vitreous cellular reaction).
Clinical charts were retrospectively reviewed and demographic information, medical history, and history of previous retinal treatments were recorded. As part of the standard clinical assessment, enrolled patients underwent clinical examination, including best-corrected visual acuity (BCVA), and multimodal imaging evaluation including color fundus photography or MultiColor imaging, near infrared reflectance (NIR), short-wave fundus autofluorescence (FAF), structural spectral-domain OCT, and OCTA. MultiColor imaging, NIR, and FAF were performed using the Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany). Structural OCT examinations were performed using the Spectralis HRA + OCT or Cirrus 5000 (Zeiss Meditech, Inc, Dublin, California, USA). Central macular thickness (CMT) was measured with the OCT volume scan and using the automated built-in software in the central 1-mm–diameter circle of the ETDRS thickness map. OCTA examinations were performed using the 3-mm × 3-mm en face image centered on the lesion (PlexElite 9000 Swept-Source OCT-A, Zeiss Meditech, Inc, or AngioVue RTVue XR Avanti, Optovue, Fremont, California, USA). All images were analyzed by a senior retinal specialist that manually adjusted all segmentation slabs provided by the OCTA software for optimal visualization of the retinal plexuses and choriocapillaris.
Relevant clinical findings available at baseline and at all follow-up examination visits were reviewed and retrospectively analyzed by 2 trained examiners (RS, EB).
Statistical Analysis
Statistical analyses were performed using SPSS software (v 20; IBM Corp, Armonk, NY, USA). In all patients, BCVA was converted to logarithm of the minimum angle of resolution (LogMAR) for statistical analysis. All values of descriptive analyses were expressed as counts and percentages for categorical variables, and as means ± standard deviations for quantitative variables. The paired student t test was used to compare BCVA and CMT between the baseline and the final follow-up, after verification of the Gaussian distribution with the Kolmogorov-Smirnov test.
P < .05 was considered statistically significant in all analyses.
Results
Six eyes of 6 white patients fulfilled the inclusion criteria and were included in the current study. One patient was included from the Department of Ophthalmology of University Vita-Salute San Raffaele, 3 from the Vitreous Retina Macula Consultants of New York, 1 from the Department of Ophthalmology of University Paris Est, and 1 from the Doheny Eye Centers in Los Angeles. The mean age of the cohort was 75 ± 10 years (median 75.5 years; range 60-88 years) and 2 patients were female and 4 were male. None of the patients endorsed a history of diabetes or other vascular diseases, although 2 patients reported a history of medically controlled essential hypertension.
At the time of nePVAC diagnosis, the mean BCVA was 20/25 Snellen equivalent (0.10 ± 0.09 logMAR; median, 0.10; range 0-0.2) and the mean CMT was 268 ± 27 μm (median, 273.5; range 218-296 μm). At baseline, none of the patients had evidence of decreased vision because of the presence of a nePVAC lesion ( Table ). Of note, all patients displayed evidence of other coincident chorioretinal diseases affecting the study or the fellow eye. Specifically, 3 of 6 patients (50%) were diagnosed with intermediate AMD, 1 of 6 patients (16.7%) with both myopia and intermediate AMD, 1 of 6 patients (16.7%) with pachychoroid disease, and 1 of 6 patients (16.7%) with an epiretinal membrane in the fellow eye (the study eye was unremarkable except for the nePVAC lesion; Table ).
| Patient No. | Sex/Age, y | Eye of Lesion | Coincident Eye Disease | BCVA Pre-exudative Stage(Snellen) | CMT Pre-exudative Stage (μm) | Intraretinal Location of nePVAC at Structural OCT | OCTA Retinal Plexus Localization | Total Follow-Up (Months) | Exudation | Time to Exudation (Months) | Final BCVA (Snellen) | Final CMT (μm) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | M/60 | OS | None | 20/20 | 218 | ONL, OPL, INL, and IPL | SCP and DVC | N/A | — | — | — | — |
| 2 | M/88 | OD | i-AMD | 20/32 | 296 | ONL, OPL, and INL | SCP and DVC | 7 | YES | 5 | 20/63 | 421 |
| 3 | M/72 | OD | i-AMD and myopia | 20/25 | 277 | OPL, INL, and IPL | SCP and DVC | 11 | NO | — | 20/32 | 274 |
| 4 | F/80 | OS | i-AMD | 20/32 | 281 | OPL, INL, and IPL | SCP and DVC | 36 | YES | 24 | 20/40 | 302 |
| 5 | M/79 | OS | i-AMD | 20/20 | 268 | ONL, OPL, INL, and IPL | SCP and DVC | 30 | YES | 20 | 20/32 | 358 |
| 6 | F/72 | OS | Pachychoroid | 20/25 | 270 | IPL and GCC | SCP | N/A | — | — | — | — |
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