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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 2  |  Issue : 2  |  Page : 449-452

Refractory perifoveal exudative vascular anomalous complex like lesion responding to intravitreal dexamethasone implant: A therapeutic challenge


1 Vitreoretinal Services, Aradhana Eye Institute, Trivandrum, Kerala, India
2 Vitreoretinal Services, Chaithanya Eye Hospital and Research Institute; Department of Research, Chaithanya Innovation in Technology and Eyecare (Research), Trivandrum, Kerala, India

Date of Submission26-Apr-2021
Date of Acceptance07-Dec-2021
Date of Web Publication13-Apr-2022

Correspondence Address:
Jay Sheth
Clinical Research Lead, Chaithanya Eye Hospital and Research Institute, Trivandrum - 695 004, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_1000_21

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  Abstract 


A 66-year-old male patient presented with the right eye (OD) decreased vision for 1 month duration. His best-corrected visual acuity (BCVA) was 6/36 in OD and 6/6 in the left-eye (OS). He had bilateral non-proliferative diabetic retinopathy (NPDR) changes with the presence of a large perifoveal aneurysmal lesion, which was diagnosed as perifoveal exudative vascular anomalous complex (PEVAC)-like lesion based on clinical evaluation, spectral domain optical coherence tomography (SD-OCT), and fundus fluorescein angiography (FFA). The patient underwent three intravitreal ranibizumab injections with minimal response. However, he showed excellent improvement in BCVA to 6/6 with complete resolution of fluid on SD-OCT after switching to intravitreal Ozurdex implant. This case highlights that an intravitreal dexamethasone implant can be considered as a viable option for the optimal management of PEVAC-like lesions, with good visual acuity outcomes and morphologic response on SD-OCT. Further studies are warranted to gain better insight into the pathogenesis of PEVAC-like lesions and the potential role and mechanism of action of intravitreal dexamethasone implant in its management.

Keywords: Dexamethasone Implant (Ozurdex), laser photocoagulation, perifoveal exudative vascular anomalous complex (PEVAC), vascular endothelial growth factor (VEGF)


How to cite this article:
Nataraj A, Sheth J, Soman M, Nair U. Refractory perifoveal exudative vascular anomalous complex like lesion responding to intravitreal dexamethasone implant: A therapeutic challenge. Indian J Ophthalmol Case Rep 2022;2:449-52

How to cite this URL:
Nataraj A, Sheth J, Soman M, Nair U. Refractory perifoveal exudative vascular anomalous complex like lesion responding to intravitreal dexamethasone implant: A therapeutic challenge. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 May 18];2:449-52. Available from: https://www.ijoreports.in/text.asp?2022/2/2/449/342864



Perifoveal exudative vascular anomalous complex (PEVAC) is an isolated perifoveal aneurysmal abnormality described by Querques et al. in 2011.[1] Although initially described as a unilateral condition occurring in an otherwise healthy subject, subsequent reports have indicated that PEVAC can be bilateral, multifocal, and can occur in patients with coexistent diabetic retinopathy (DR), age-related macular degeneration (AMD), and myopic macular degeneration.[2],[3],[4]

PEVAC lesions are associated with retinal hemorrhages, intraretinal fluid, and hard exudates clinically.[1] On spectral domain optical coherence tomography (SD-OCT), it is seen as a circular lesion with hyperreflective walls and variable internal reflectivity, along with intraretinal cystic changes and hard exudates.[1],[4] Angiographically, it appears as a well-defined hyperreflective lesion with variable leakage on fundus fluorescein angiography (FFA), while indocyanine green angiography (ICGA) does not show any leakage.[5] On optical coherence tomography angiography (OCTA), PEVAC shows a flow signal corresponding to the aneurysm, which is connected to the retinal capillary plexuses.[5]

Management of PEVAC is perplexing since these lesions are typically unresponsive to anti-vascular endothelial growth factor (anti-VEGF) therapy or laser photocoagulation.[4],[5] We report here, to our knowledge, the first case of a patient with PEVAC-like lesion with mild non-proliferative diabetic retinopathy (NPDR) changes, non-responsive to three doses of intravitreal anti-VEGF therapy, in whom resolution of edema was achieved by intravitreal dexamethasone implant (Ozurdex).


  Case Report Top


A 66-year-old male patient, with a history of diabetes and hypertension for 5 years, presented with decreased vision in the right eye (OD) of 1 month duration. His best-corrected visual acuity (BCVA) was 20/120 in OD and 20/20 in the left eye (OS). Both eyes' (OU) anterior segment examination was normal. OU fundus examination showed mild NPDR changes [Figure 1]a and [Figure 1]b; [Figure 2]a and [Figure 3]a. Additionally, OD showed the presence of a large perifoveal aneurysmal lesion that was associated with intraretinal fluid, hemorrhage, and hard exudates [Figure 1]a. On SD-OCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany), the PEVAC-like lesion appeared as a classic round intraretinal lesion with hyperreflective walls and central moderately hyperreflective cavity [Figure 2]e,[Figure 2]f,[Figure 2]g, surrounded by intraretinal cysts and hyperreflective lesions corresponding to hard exudates. OS SD-OCT was normal [Figure 3]a and [Figure 3]b. Fundus autofluorescence (FAF) demonstrated a central hyperautofluorescence corresponding to the lesion, surrounded by hypoautofluorescence [Figure 2]b. FFA showed a well-defined hyperfluorescent lesion with leakage in the late frames [Figure 2]c and [Figure 2]d. OS FFA confirmed the presence of mild NPDR changes [Figure 3]b and [Figure 3]d.
Figure 1: Fundus photography of both eyes showing the presence of mild NPDR changes (a and b). Additionally, there was presence of a large perifoveal microaneurysm (purple arrow, (a) corresponding to PEVAC lesion accompanied by hemorrhage and hard exudates. NDPR = non-proliferative diabetic retinopathy, PEVAC = perifoveal exudative vascular anomalous complex

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Figure 2: Multimodal imaging of PEVAC lesion in the right eye. Fundus photography showing the PEVAC lesion (purple arrow, a), which demonstrates central hyperautofluorescence on fundus autofluorescence (red arrow, b). On fundus fluorescein angiography, the PEVAC lesion showed central hyperfluorescence in early images (blue arrow, c), with fuzziness in late phase suggestive of leakage (blue arrow, d). On SD-OCT, there was significant cystoid macular edema in the foveal sections (e). The PEVAC lesion was seen as a round intraretinal lesion with hyperreflective walls and central moderately hyperreflective cavity (yellow arrow in f and g [zoomed SD-OCT image]), surrounded by intraretinal cysts and hyperreflective lesions suggestive of hard exudates. PEVAC = perifoveal exudative vascular anomalous complex, SD-OCT = spectral domain optical coherence tomography

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Figure 3: Fundus photograph of the left eye (a) showed presence of mild non-proliferative diabetic retinopathy (NPDR) which was confirmed on fundus fluorescein angiography (FFA; c and d). Spectral-domain optical coherence tomography (SD-OCT) was normal (d)

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Based on the characteristic clinical and multimodal imaging findings, the patient was diagnosed as having OD PEVAC-like lesion and underwent three intravitreal ranibizumab injections, which gave a minimal response on SD-OCT [Figure 4]a,[Figure 4]b,[Figure 4]c,[Figure 4]d and no improvement in BCVA. Subsequently, the patient underwent an intravitreal dexamethasone implant (Ozurdex) in OD. The patient responded dramatically and there was a significant improvement in BCVA to 20/20 with the resolution of edema at 1 and 3 months, respectively [Figure 4]e. However, the PEVAC-like lesion persisted on SD-OCT at follow-up visits [Figure 4]f. At 4 months post-Ozurdex implant, the patient presented with a drop in OD BCVA to 20/80. SD-OCT demonstrated recurrence of macular edema with the persistence of PEVAC-like lesion [Figure 4]g and [Figure 4]h. The patient has been scheduled for the second dose of intravitreal Ozurdex injection.
Figure 4: Time course of PEVAC lesion treatment. At baseline, significant CME was noted (a) along with the PEVAC lesion (purple arrow, b). A minimal change was noted in CME (c) and PEVAC lesion (red arrow, d) after three doses of intravitreal ranibizumab injections were given. After intravitreal dexamethasone implant was given, there was complete resolution of CME (e), but the PEVAC lesion persisted (blue arrow, f) at 1 and 3 months, respectively. However, the patient presented with a recurrence of CME at 4 months (g), with the persistence of PEVAC lesion (yellow arrow, h). CME = cystoid macular edema, PEVAC = perifoveal exudative vascular anomalous complex, SD-OCT = spectral domain optical coherence tomography

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  Discussion Top


According to the original definition, a PEVAC lesion is a large, isolated perifoveal aneurysm occurring in the absence of any retinal vascular, or inflammatory pathology.[1] Though initially described to be present only in an otherwise healthy individual with normal eyes, newer associations of this entity have been reported in the literature. Sacconi et al.[4] evaluated 15 eyes with PEVAC and have defined an expanded spectrum of the association including AMD and myopic macular degeneration. Fernández-Vigo et al.[6] have described an atypical case of PEVAC with bilateral presentation and multifocal lesions in one eye. The presence of PEVAC in a patient of advanced lamellar macular hole (LMH) with lamellar hole–associated epiretinal proliferation (LHEP) and suboptimal response to anti-VEGF therapy has been reported in the literature.[7] Recently, it has been shown that diabetic patients too can demonstrate these lesions in the presence or absence of DR changes.[3],[5] Likewise, in the present case report, the patient had concurrent mild NPDR changes in both eyes, along with the PEVAC-like lesion in one eye. PEVAC is a morphologic terminology and not an etiological diagnosis; considering its existence in various pathologies like myopia, AMD, DR, and so on, the authors have preferred to use the term “PEVAC-like lesion” rather than “PEVAC lesion” itself.

Larger microaneurysms are routinely seen in patients with DR.[5],[8] On SD-OCT, they too show hyperreflective wall with central hyporeflectivity or hyperreflectivity.[5],[8] However, such large microaneurysms are usually seen in patients with significant simultaneous DR changes along with chronic edema. Also, these eyes usually respond well to intravitreal anti-VEGF therapy.[5],[7] On the other hand, in the present case, the patient had very mild DR changes based on the clinical and angiographic evaluation. With an additional non-responsiveness to anti-VEGF therapy and based on classical multimodal imaging features, we established the diagnosis of PEVAC-like lesion with mild NPDR changes.

Treatment of PEVAC or PEVAC-like lesions is challenging since they are very resistant to anti-VEGF treatment.[4],[5] Sacconi et al.[4] have also reported no difference in BCVA or central macular thickness between eyes of patients who had received anti-VEGF therapy and those who did not receive any treatment. They have even shown fluctuation in the intraretinal fluid, which may impact the assessment of true response to anti-VEGF treatment. Additionally, even spontaneous improvement of PEVAC lesions has been reported in the literature.[4] In the current report, the patient did not respond to three doses of ranibizumab injections. Laser photocoagulation is another treatment that has been tried with limited success.[5] Mrejen et al.[9] have shown resolution of exudates with laser photocoagulation, while Venkatesh et al.[5] have shown the progression of PEVAC despite laser treatment. Nonetheless, laser photocoagulation has its limitations since the PEVAC or PEVAC-like lesions are very close to the fovea and there is a risk of permanent visual scotomas. In our patient too, laser photocoagulation was not considered since the lesion was reasonably close to the fovea.

The exact pathogenesis of PEVAC or PEVAC-like lesions is still unclear. It has been hypothesized to be due to focal or progressive endothelial cell degeneration/injury, which accounts for non-responsiveness to anti-VEGF treatment.[1],[2] Along with endothelial cell injury, the associated reduction in pericyte cell protection due to basement membrane breakdown has also been proposed for the occurrence of PEVAC lesions.[10] While the inciting events for these pathological changes remain uncertain, potential low-grade inflammation could be one possibility. Corticosteroid agents help to maintain cellular tight junction integrity by stimulating tight junction protein expression and inhibiting oxidative stress–induced disruption of tight junction proteins.[11] Additionally, they also reduce vascular permeability and potentiate retinal fluid clearance by mediating onto the retinal channels that maintain retinal fluid movement, namely, the potassium and transcellular aquaporin-4 (AQP4) channels.[11]

The exact mechanism for Ozurdex response in PEVAC-like lesions remains unclear, but possible anti-permeability, anti-inflammatory, and anti-angiogenic mechanisms can be proposed. The potential role of inflammatory markers in PEVAC-like lesions needs to be explored further by evaluating the serum and vitreous samples of these patients. We envisage normal serum levels since the patient is usually otherwise healthy systemically. However, since PEVAC-like lesions are isolated aneurysms, elevated levels of local ocular inflammatory mediators could be present.


  Conclusion Top


In conclusion, an intravitreal dexamethasone implant may be a promising alternative in the management of PEVAC-like lesions with DR, which are typically refractory to anti-VEGF therapy. Additional histopathologic and biomarker studies are warranted to gain better insight and evidence into its mechanism of action and the potential role of a local inflammatory milieu in the pathogenesis of PEVAC-like lesions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Querques G, Kuhn D, Massamba N, Leveziel N, Querques L, Souied EH. Perifoveal exudative vascular anomalous complex. J Fr Ophtalmol 2011;34:559.e1-4.  Back to cited text no. 1
    
2.
Fernández-Vigo JI, Burgos-Blasco B, Dolz-Marco R, Jiménez-Santos M, López-Guajardo L, Donate-López J. Atypical perifoveal exudative vascular anomalous complex (PEVAC) with multifocal and bilateral presentation. Am J Ophthalmol Case Rep 2020;21;18:100717. doi: 10.1016/j.ajoc. 2020.100717.  Back to cited text no. 2
    
3.
Zhang Z, Xu L, Wu Z, Zhang J. Case report: Perifoveal exudative vascular anomalous complex in a Chinese patient with diabetes mellitus. Optom Vis Sci 2019;96:531-5.  Back to cited text no. 3
    
4.
Sacconi R, Freund KB, Yannuzzi LA, Dolz-Marco R, Souied E, Capuano V, et al. The expanded spectrum of perifoveal exudative vascular anomalous complex. Am J Ophthalmol 2017;184:137-46.  Back to cited text no. 4
    
5.
Venkatesh R, Yadav NK, Bavaharan B, Prabhu V, Sinha S. Multimodal imaging in perifoveal exudative vascular anomalous complex with co-existent diabetic retinopathy. Clin Exp Optom 2019;102:528-32.  Back to cited text no. 5
    
6.
Fernández-Vigo JI, Burgos-Blasco B, Dolz-Marco R, Jiménez-Santos M, López-Guajardo L, Donate-López J. Atypical perifoveal exudative vascular anomalous complex (PEVAC) with multifocal and bilateral presentation. Am J Ophthalmol Case Rep 2020;18:100717. doi: 10.1016/j.ajoc. 2020.100717.  Back to cited text no. 6
    
7.
Siedlecki J, Vounotrypidis E, Vogt D, Wolf A, Priglinger SG, Schumann RG. Lamellar hole-associated epiretinal proliferation presenting with perifoveal exudative vascular anomalous complex. Am J Ophthalmol Case Rep 2019;14:112-6.  Back to cited text no. 7
    
8.
Bourhis A, Girmens JF, Boni S, Pecha F, Favard C, Sahel JA, et al. Imaging of macroaneurysms occurring during retinal vein occlusion and diabetic retinopathy by indocyanine green angiography and high resolution optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 2010;248:161-6.  Back to cited text no. 8
    
9.
Mrejen S, Le HM, Nghiem-Buffet S, Tabary S, Quentel G, Cohen SY. Insights into perifoveal exudative vascular anomalous complex. Retina 2020;40:80-6.  Back to cited text no. 9
    
10.
Sacconi R, Borrelli E, Sadda S, Corradetti G, Freund KB, Yannuzzi LA, et al. Nonexudative perifoveal vascular anomalous complex: The subclinical stage of perifoveal exudative vascular anomalous complex? Am J Ophthalmol 2020;218:59-67.  Back to cited text no. 10
    
11.
Dugel PU, Bandello F, Loewenstein A. Dexamethasone intravitreal implant in the treatment of diabetic macular edema. Clin Ophthalmol 2015;9:1321-35.  Back to cited text no. 11
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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