Pediatric vitreoretinal surgery is a collective term for surgical treatments performed for vitreoretinal diseases that occur from infancy to childhood. The target diseases are diverse.
Retinopathy of Prematurity
Definition: Abnormal retinal vascular development in preterm and low birth weight infants. Abnormal neovascular proliferation and traction lead to retinal detachment.
Importance: A leading cause of childhood blindness worldwide. It accounted for approximately 11% of childhood blindness in the 1990s and about 20% in 2010. 3)
FEVR / PFV
Familial exudative vitreoretinopathy (FEVR): Retinal vascular developmental failure due to mutations in Wnt signaling pathway genes (FZD4, LRP5, etc.). It presents with fundus findings similar to retinopathy of prematurity.
Persistent fetal vasculature (PFV): A congenital anomaly in which the fetal hyaloid vasculature fails to regress. It is often unilateral.
Coats disease and pediatric RD
Coats disease: Exudative retinal detachment caused by abnormal dilation and leakage of retinal capillaries. It is more common in boys and is usually unilateral.
Pediatric retinal detachment: Rhegmatogenous retinal detachment triggered by lattice degeneration or trauma. It can also occur as a late complication of untreated retinopathy of prematurity. 1)
The pathophysiology of retinopathy of prematurity is explained by a two-phase model. In phase 1 (22–30 weeks gestational age), high oxygen environment causes arrest of retinal vascular development. In phase 2 (around 30–34 weeks gestational age), relative hypoxia leads to excessive VEGF production, causing abnormal neovascularization. 3)
In pediatric eyes, the pars plana is underdeveloped, the lens is large, and the sclera is thin, so the same approach as in adults cannot be used. The vitreous is more strongly adherent to the retina than in adults, and inducing a posterior vitreous detachment (PVD) carries a risk of iatrogenic retinal tears. Postoperative proliferative changes also tend to be more severe.
Since children cannot self-report symptoms, observation by parents and during health checkups is important.
The stage of retinopathy of prematurity is evaluated based on ICROP3 (revised in 2021). 3)
| Classification Axis | Description |
|---|---|
| Zone | Zone I: posterior pole center, Zone II: middle, Zone III: periphery |
| Stage | 1: demarcation line, 2: ridge, 3: neovascularization, 4: partial detachment, 5: total detachment |
Plus disease is characterized by vascular tortuosity and dilation in the posterior pole (involving 2–4 quadrants or more) and is an important indicator for treatment. 3)
A long-term follow-up study of untreated retinopathy of prematurity (186 cases, 363 eyes) confirmed late complications such as lattice degeneration, atrophic holes, and retinal detachment. 1)
The severity of cicatricial retinopathy of prematurity is evaluated using the Ministry of Health and Welfare classification (grades 1–5). Grade 1: only minor peripheral changes. Grade 2: vitreous strands or retinal folds. Grade 3: macular traction. Grade 4: vitreous traction and retinal detachment (not involving the macula). Grade 5: funnel-shaped total retinal detachment.
Leukocoria is a common sign of several serious diseases and requires prompt differential diagnosis.
| Disease | Distinguishing features |
|---|---|
| Retinopathy of prematurity Stage 4–5 | History of preterm birth or low birth weight |
| Persistent fetal vasculature | Unilateral, may be associated with microphthalmia |
| Retinoblastoma | Life-threatening, requires urgent evaluation |
| Coats disease | More common in boys, exudative retinal detachment |
Leukocoria can be a sign of life-threatening diseases such as retinoblastoma. It is important to have the patient see an ophthalmologist promptly. Examination includes dilated fundus examination, ultrasound, and if necessary, CT scan to differentiate the cause.
The development of retinopathy of prematurity is strongly associated with preterm birth and low birth weight.
In Japan, screening for retinopathy of prematurity is indicated for infants born at <34 weeks of gestation or with a birth weight ≤1,800 g.
FEVR is caused by mutations in genes involved in the Wnt signaling pathway. Causative genes include FZD4, LRP5, NDP, TSPAN12, and KIF11. Inheritance is often autosomal dominant but with incomplete penetrance, and severity can vary greatly even within the same family.
PFV is usually unilateral and non-hereditary. It occurs when the fetal hyaloid vasculature fails to regress normally. No specific risk factors have been identified.
Screening begins at 31–32 weeks of gestational age or 4–6 weeks after birth, whichever is later. The basic examination is dilated retinal observation using indirect ophthalmoscopy or a wide-angle fundus camera (e.g., RetCam).
Development of AI-based retinopathy of prematurity screening systems using wide-field fundus camera images is progressing. 3) It is expected to be applied for early detection and severity assessment in areas with few specialists. High sensitivity and specificity have been reported for detecting retinopathy of prematurity, and it is evaluated as a scalable screening tool in regions with limited medical resources. 3)
Circumferential photocoagulation of the avascular retina is established as standard treatment. It promotes regression of neovascularization and prevents progression to retinal detachment. The main treatment indications are Stage 3 or higher with Zone I lesions and plus disease.
Intravitreal injection of VEGF inhibitors (e.g., bevacizumab, ranibizumab) for retinopathy of prematurity has become widely performed. 3)
Consider for tractional retinal detachment in Stage 4A/4B retinopathy of prematurity. The retina is reattached using a circumferential band or segmental buckle. In children, the buckle may loosen as the eye grows postoperatively, requiring later removal.
This surgery aims to remove proliferative traction membranes and reattach the retina, and is the primary surgical treatment for Stage 4–5 retinopathy of prematurity. Preserving the lens reduces the risk of postoperative amblyopia. 3)
The approximate success rates (retinal reattachment rates) of LSV by stage are shown below. 3)
| Stage | Approximate Success Rate |
|---|---|
| Stage 4A | 74–91% |
| Stage 4B | 62–92% |
| Stage 5 | 22–48% |
There is a risk of late postoperative redetachment. Kondo et al. (2009) reported late redetachment after surgery for Stage 4B/5 retinopathy of prematurity, indicating the need for long-term follow-up. 2)
Due to anatomical differences from adults, the following measures are necessary.
Cataract may occur as a postoperative complication. 3) Prompt optical correction and occlusion therapy are required to prevent amblyopia.
In Stage 5 (funnel-shaped total retinal detachment), the retinal reattachment rate with LSV is only 22–48%. 3) Visual function recovery is limited, and the goal of surgery is often to achieve or maintain light perception. Early surgical intervention at Stage 4A greatly influences visual prognosis.
The development of retinopathy of prematurity is understood as a biphasic vascular pathology. 3)
Phase 1 (vaso-obliteration, 22–30 weeks gestational age): The postnatal hyperoxic environment (oxygen supplementation in the incubator) suppresses the growth of retinal blood vessels that would normally develop under hypoxic conditions. Production of VEGF and IGF-1 decreases, and existing blood vessels also regress. In preterm infants, IGF-1 levels are low due to the loss of maternal and amniotic fluid supply, contributing to the arrest of vascular development in phase 1.
Phase 2 (vasoproliferation, around 30–34 weeks gestational age): Relative hypoxia occurs in the avascular peripheral retina as metabolic demands increase. VEGF is overproduced, leading to abnormal arteriovenous shunts (Stage 1 and 2), neovascularization (Stage 3), and Plus disease. Persistent elevation of VEGF progresses to fibrovascular proliferation, scarring, and tractional retinal detachment.
FEVR is a retinal vascular developmental disorder caused by genetic mutations in the Wnt signaling pathway (FZD4, LRP5, NDP, TSPAN12, etc.). The extension of retinal blood vessels to the periphery is insufficient, leading to exudation into avascular areas, neovascular proliferation, and tractional retinal detachment. The clinical picture resembles retinopathy of prematurity, but is characterized by the absence of preterm birth and a slowly progressive course.
PFV results from the failure of the primary vitreous (fetal vasculature including the hyaloid artery) to regress normally during embryonic development. It is usually unilateral and classified into posterior, anterior, and mixed types. Traction from the persistent tissue leads to elongation of ciliary processes, retinal folds, lens opacities, and retinal dysplasia.
Systems are being developed in which AI analyzes retinal images captured by wide-angle fundus cameras to determine the stage of retinopathy of prematurity and detect Plus disease. 3)
Retinal image diagnosis of retinopathy of prematurity by experts or AI-assisted systems has shown high sensitivity and specificity in detecting treatment-requiring retinopathy of prematurity, and is being evaluated as a scalable screening tool in regions with limited medical resources. 3)
Caffeine is widely used as a treatment for apnea of prematurity. Its effect on the incidence and severity of retinopathy of prematurity (ROP) is being studied. 3) However, clear evidence has not yet been established, and caffeine administration primarily for ROP is not currently standard treatment.
Hamad et al. (Ophthalmol Retina, 2020) reported a long-term follow-up study of 186 cases (363 eyes) of untreated ROP. Various late complications such as lattice degeneration, atrophic holes, and retinal detachment were observed. 1) Comparison with treated cases supported the long-term benefit of early treatment intervention.
Kondo et al. (Am J Ophthalmol, 2009) followed the long-term course of surgical cases of Stage 4B/5 ROP and reported late retinal redetachment after surgery. 2) Even in successful surgeries, redetachment may occur several years later, highlighting the importance of regular long-term follow-up.
Vision after treatment varies greatly depending on the stage, timing of treatment, and involvement of the macula. If treatment is successful early in Stage 4A or below, relatively good vision can be expected. In retinal detachment involving the macula (Stage 4B or higher), visual prognosis is limited, and long-term amblyopia treatment and follow-up are important. 3)
