Pediatric Retinal Detachment Associated With FEVR

Familial exudative vitreoretinopathy (FEVR) is a heritable vitreoretinal disorder characterized by abnormal retinal angiogenesis.¹ FEVR is generally bilateral and asymmetric with a mean age of presentation of 6 to 8 years of age.^1-3 Incomplete peripheral retinal vascularization and subsequent retinal ischemia are the hallmark features of FEVR.^3,4 The resultant hypoxia promotes abnormal neovascularization, which, over time, results in secondary complications such as neovascularization, vitreoretinal traction, peripheral fibrovascular proliferation, macular ectopia, subretinal and intraretinal exudation, retinal folds, vitreous hemorrhage, and retinal detachment (RD; Figures 1 and 2).^2-6 Surgical management of FEVR with scleral buckling (SB), vitrectomy, or both has a reattachment rate of 85.5% with promising visual outcomes.⁷

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Figure 1. FEVR macula-off RRD with peripheral retinal avascularity and neovascularization can be seen on fundus photography (A-C) and FA (D-F).

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Figure 2. Ultra-widefield color fundus photography and FA demonstrate tractional RD with exudation and peripheral leakage due to neovascularization in a patient with FEVR.

UNDERSTANDING THE PATHWAYS

The Wnt signaling pathway regulates retinal development, maintenance, and repair in the eye.^8,9 This norrin-driven pathway promotes the development of normal capillary beds with non-fenestrated vessels, and when the pathway breaks down in FEVR, the capillary beds are impaired. This leaves an underdeveloped eye and creates a large area of avascular peripheral retina with an impaired Wnt pathway. All forms of FEVR exhibit some degree of blood-retina barrier breakdown; some will have very poor tight junctions, ischemic drive, and continued exudation, while others may also have frank bleeding and neovascularization.^8,9

ROLE OF IMAGING AND ANGIOGRAPHY

Widefield imaging allows more detailed views of the retinal periphery, which is particularly beneficial in pediatric retinal pathologies, such as retinopathy of prematurity, Coats disease, and FEVR (Figures 3 and 4). Fluorescein angiography (FA) is essential for accurate diagnosis and successful treatment of patients with FEVR, as many signs appear in the peripheral retina. Peripheral retinal nonperfusion, vessel pruning, avascularity, neovascularization, straightening of vessels, and peripheral vascular anastomoses are typical retinal vascular findings that can be demonstrated on widefield FA. Importantly, FA is useful to guide treatment. It helps to identify the border between the vascular and avascular retina better than fundus visualization alone. It also aids in better defining complete retinal ablation.

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Figure 3. Color montage imaging shows straightening of vessels with peripheral retinal avascularity and localized RD in the inferotemporal quadrant. Pre-SB (A), widefield fundus angiography demonstrates areas of neovascularization nasal to the disc and peripheral avascular areas (B). Status 7 days post-SB (C).

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Figure 4. Sibling screening revealed similar findings across both eyes with attached retinas. Color fundus photography (A, B) and widefield angiography (C, D) show straightening of vessels and avascular areas with multiple lattices in the retinal periphery. As the patient had a sibling with RD, both eyes were lasered.

OUR EXPERIENCE

We conducted a prospective interventional study of 14 eyes of 13 children from 5 to 16 years of age with rhegmatogenous RD (RRD) secondary to FEVR and a mean preoperative VA in the surgical eye of 2/60.¹⁰ Diagnosis of FEVR was based on clinical history/examination, FA, and family screening—specifically sibling screening (Figure 4). The diagnostic criteria used to confirm FEVR were: 1) lack of peripheral retinal vascular development in at least one eye, 2) birth at full term or preterm with a disease course incompatible with ROP, and 3) variable degrees of nonperfusion, vitreoretinal traction, subretinal exudation, or retinal neovascularization occurring at any age. The inclusion criteria for the study were: 1) a diagnosis of FEVR, 2) the presence of macula-off RRD, for which the patient underwent surgical intervention, and 3) age ≤ 18 years old. Both eyes of each patient were classified based on the FEVR staging system proposed by Kashani et al.²

On fundus evaluation, stage 4A FEVR was noted in six eyes (42.86%), stage 4B FEVR in two eyes (14.28%), and stage 5A in six eyes (42.86%). The fellow eye was phthisical in one patient and normal in another, while stage 1A FEVR was seen in four eyes, stage 1B in one eye, and stage 2A in five eyes.

Surgical Management

The primary objective of surgical management in FEVR is to relieve the anteroposterior and tangential tractions and address the avascular retinal tissue. The intraocular VEGF load can be reduced by a thorough vitrectomy and peripheral retinal tissue ablation using laser photocoagulation. Inducing a posterior vitreous detachment and completing the vitrectomy is critical to relieve the traction on the retina. SB is vital to mitigate the additional peripheral traction.¹¹ The surgical approach taken depends on the type and location of the RD, as well as the extent of fibrovascular proliferation.

In our study, silicone tires of suitable dimensions along with a 360° encircling buckle were used for patients with less than two quadrants of peripheral retinal proliferation. For patients with at least two quadrant involvement of fibrovascular proliferation or fibrovascular proliferation presence at the posterior pole, a standard three-port, 23-gauge vitrectomy was performed (Figure 5). Triamcinolone acetonide was used for the induction of the posterior vitreous detachment. Extensive vitrectomy was done, especially at the vitreous base and around the fibrovascular proliferative tissues. Careful resection and delamination of the fibrovascular tissue was performed to the maximum extent possible. Retinal reattachment was achieved followed by endophotocoagulation and/or transscleral cryotherapy and silicone oil tamponade. The decision to perform lensectomy was made for patients with fibrovascular proliferation around the ora and/or at the posterior lens surface.

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Figure 5. Fundus photos of patients with FEVR and RRD demonstrate the absence of macular drag in one case (A) and proliferative vitreoretinopathy with foveal drag in another (B). After vitrectomy with silicone oil injection in case B, there was complete retinal reattachment (C).

After surgery, the patients were evaluated on day 1, week 1, months 1 and 3, and thereafter every 3 to 6 months, depending on the course of the disease. Silicone oil was removed 6 to 9 months following the primary surgery.

Of the 14 eyes with RRD secondary to FEVR, four (28.57%) underwent SB with silicone oil injection, and the remaining 10 (71.43%) underwent primary vitrectomy with silicone oil injection.

After a mean follow-up of 3.32 years, the mean VA improved from 2/60 to 6/24 (P < .00001) at the final visit. Successful reattachment was achieved in 13/14 eyes.

TAKEAWAYS

FEVR is a lifelong disease that requires regular examinations and can give rise to RRD at an early age. A meticulous clinical and angiographic evaluation of each eye can help with the correct diagnosis and appropriate treatment. Timely surgical intervention, either with SB or vitrectomy, and vigilant follow-ups are highly effective in achieving anatomical and functional long-term success.