ROP is characterized by a relatively predictable timeline of progression. Initial manifestations of the disease are usually seen approximately 32 weeks postmenstrual age (PMA), and the threshold for laser ablation is reached at a mean of 37 weeks PMA [37, 43]. Retinal detachment after appropriate laser ablation occurs at a mean of 41 weeks PMA [42]. The most dramatic exception to this timeline is aggressive posterior ROP that is characterized by rapid progression of zone 1 or posterior zone 2 plus disease and ill-defined retinal neovascularization to retinal detachment [22].

The rapidity of disease progression correlates to some degree with the level of retinal vascular activity at the time of retinal detachment. Surgery for stage 4A ROP targets interruption of transvitreal proliferative condensations. For this reason, vascular activity is rarely a reason to defer surgical intervention. In general, once surgical intervention is necessary for stage 4A ROP, the earlier the procedure is performed, the better to minimize the extent of the detachment.

Surgery for stages 4B and 5 ROP typically entails the mechanical removal of preretinal proliferation. An eye with a high degree of vascular activity, as represented by plus disease, florid retinal neovascularization, and rubeosis iridis, is likely to encounter significant intraoperative bleeding. In eyes with stage 4B or stage 5 detachments in the setting of significant vascularity, it is usually necessary to wait until 48–52 weeks PMA for vascular activity to decrease to intervene [18].

In most stage 4A and many stage 4B ROP detachments, it is possible to relieve traction with a lens-sparing vitrectomy (LSV). The eye is entered at the pars plicata, approximately 0.5 mm posterior to the limbus. A two-port approach using an infusing light pipe or pic and three-port approach using a separate infusion line have both been reported with similar success rates [6, 21, 26, 31]. A core vitrectomy is carefully performed with attention to the vectors of traction. Specifically, an effort should be made to address the transvitreal ridge to ridge tissue, ridge to periphery, ridge to lens, and optic nerve head to the ridge (Fig. 2.2). In many cases, successful release of traction is evident during the case with relaxation of the tented retina. When the dissection is complete, a fluid-air exchange is performed, and the sclerotomies are sutured. Persistent subretinal fluid is expected at the conclusion of the case and will reabsorb over the course of weeks to months. Similarly, this approach is effective in treating the tractional component of stage 3B and stage 4B FEVR detachments [38].

In some cases of stage 4 ROP-related retinal detachments, anterior ridge to ciliary body tissue cannot be safely dissected by a transvitreal approach without damaging the crystalline lens. In such instances, the surgeon can cleave these anterior bands at the time of entry into the eye by placing the MVR blade through the sheet of tissue and drawing back, an approach described as an ab interno incision [20]. The tissue can be incised parallel to the lens capsule once the blade has entered into view; however, care must be taken to avoid the lens equator on entry. Safe entry is accomplished by pointing the instrument posteriorly, parallel to the visual axis. If the anterior bridging tissue between the retina and the lens-ciliary body diaphragm cannot be safely separated through the pars plicata incisions, then a lensectomy and an anterior approach may be necessary to safely relieve vitreoretinal traction and allow for retinal relaxation.

In some cases of PFVS, the stalk tissue is attached eccentric to the visual axis and extends posteriorly. Traction is exerted on the posterior lens surface and on the posterior pole. To address this traction, a lens-sparing technique with entry similar to a stage 4 ROP-related detachment can be performed. In contrast to the approach to ROP-related retinal detachment, the first step is to divide the stalk anteriorly without vitrectomy [45]. This is accomplished with an MPC type scissor, with careful attention to avoid manipulating the stalk, which can result in damage to the posterior lens capsule. Once the stalk has been divided, the anterior remnant is not manipulated. This is to avoid damage to the intrinsic retinal vessels and folds of retinal tissue, which may be dragged into the stalk as far as two-thirds the distance toward the lens (Fig. 2.3). The posterior stalk often retracts several millimeters immediately following transection, demonstrating the effect of the traction (Fig. 2.3). A limited core vitrectomy is then performed and the sclerotomies are closed. This approach has been demonstrated to improve function with resolution of strabismus without muscle surgery in the majority of children with this presentation [45].

In cases of advanced retinal detachment or a poor view posterior to the lens, including stage 5 ROP, stage 5 FEVR, and PFVS cases with diffuse retrolental plaques, the risk of creating an iatrogenic retinal break may outweigh the benefits of performing lens-sparing surgery, and an anterior (translimbal) approach to lensectomy and vitrectomy may be preferable. When an anterior approach is desired, an inferotemporal or inferior infusion cannula is placed at the limbus to stabilize the anterior chamber initially and the unicameral anterior-posterior chamber subsequently. Limbal incisions are then made superonasally and superotemporally. The pediatric crystalline lens is aspirated with a vitrector once the anterior lens capsule has been opened. Importantly, the goals of lensectomy in such a situation differ from those of the removal of an uncomplicated congenital cataract. The benefits of preserving capsular support for potential secondary intraocular lens implantation in the future are outweighed by the likelihood of residual capsule serving as a scaffold for preretinal proliferation and circumferential vitreoretinal contraction. Once the residual capsule and the ciliary body are drawn into a contractile anterior ring, the ensuing hypotony may be difficult to treat both because the anterior contractile ring is difficult to visualize and safely dissect and because the ciliary body sustains permanent injury. Even in cases of chronic total retinal detachment with lenticuloretinal apposition, capsular material can generally be stripped away from the retina without causing retinal breaks. The surgeon may then proceed with anterior dissection of preretinal proliferative tissue, hyaloidal organization, or anterior stalk tissue.

As in adult vitreoretinal surgery, the goals of pediatric vitreoretinal surgery are generally evident at the outset of the procedure: removal of significant media opacities, relieving of the transvitreal or vitreoretinal traction, peeling, and removal of the proliferative tissue. However, the risks of operating in an aggressive manner are far greater in children than in adults. Simply put, perfection is expensive in terms of risk of complications. In particular, the consequences of creating an iatrogenic retinal break can be devastating in children because of the massive proliferative response that often ensues [19]. As the pediatric vitreous is relatively well formed and is adherent to the retinal surface, the surgeon may be tempted to shave close to the retina with the vitreous cutter to remove the preretinal vitreous cortex. Such a maneuver is useful only rarely in pediatric cases and should be avoided in the absence of very specific relevant surgical goals. Performing a vitrectomy without complete removal of the posterior hyaloid in a child may lead to posterior hyaloidal contraction syndrome and retinal detachment, but in our experience this rare sequela does not warrant aggressive removal of adherent vitreous cortex on a routine basis [23].

The vitreoretinal adhesion is mediated in part by laminin and fibronectin [25]. Plasmin enzyme, either the intact protein procured from blood obtained from the patient (autologous) or a parent (heterologous) or the recombinant fragment ocriplasmin (Jetrea), can be administered to cleave laminin and fibronectin and facilitate posterior vitreous detachment [12, 30]. In adult cases with unusually strong vitreoretinal adhesions, such as in proliferative diabetic retinopathy, plasmin facilitates the surgical induction of posterior vitreous detachment [3, 52]. Ocriplasmin has also been evaluated for the treatment of vitreomacular adhesion in two randomized controlled studies and was shown to induce a posterior vitreous detachment in 30 % of patients [48].

A subset of pediatric vitreoretinal surgery requires successful peeling of preretinal membranes or the posterior hyaloid to achieve primary surgical goals, and plasmin may be useful in these situations. The posterior hyaloidal contraction syndrome is perhaps the most direct example, as a persistent vitreoretinal adhesion combined with hyaloidal contraction is relieved by successful vitreoretinal separation [23]. Preretinal proliferative membranes are also central components to the pathology of advanced cases of ROP, FEVR, CXLRS, and PVR-associated retinal detachments. The use of plasmin enzyme or ocriplasmin may facilitate the removal of such membranes and reduce the risk of creating an iatrogenic retinal break during membrane peeling (for review, see [55]). In young children who cannot tolerate an intravitreal injection in the clinic, plasmin is injected into the vitreous cavity following induction of general anesthesia, and surgery initiated approximately 30 min thereafter.

Stalk tissue extending from the disk toward the posterior aspect of the crystalline lens is characteristic of PFVS [16]. The stalk tissue represents residual hyaloidal vasculature, which may include elements within the vitreous cavity, as well as remnants of the tunica vasculosa lentis, which surrounds the lens. The hyaloid system normally begins to regress by 12 weeks’ gestation and is completely regressed by 35–36 weeks’ gestation [59]. The main hyaloid trunk is the last element to undergo regression. As a result, persistent fetal vasculature is often present in pediatric vitreoretinopathies where the normal development program failed, and the surgeon must differentiate persistent stalk tissue from a retinal fold to identify and address the pathology.

The stalk tissue may be fibrous or contain patent vessels. In ROP, the stalk tissue can be adherent to the detached retina, complicating the surgical dissection [11]. FEVR is a disease characterized by radial retinal folds, which may be pulled anteriorly by transvitreal traction toward the lens-ciliary body diaphragm. Persistent fetal vasculature may be found along the edge of the fold, and the fold itself may be difficult to identify clinically when viewed on end (Fig. 2.4). In such a case, if a knifelike fold is mistakenly identified as a stalk, the diagnosis of FEVR may be missed entirely [40]. A limited clinical examination in an uncooperative child may limit the physician’s ability to distinguish between a fold and a stalk, and examination under anesthesia may be necessary.

Primary avascularity of the peripheral retina is a key feature of several pediatric vitreoretinopathies [5, 22]. In ROP, the staging system depends on the ability of the clinician to identify the line (stage 1) or ridge (stage 2) separating vascular and avascular retina and any neovascularization that may extend from the ridge (stage 3). VEGF is produced by the avascular peripheral retina, thereby fostering retinal neovascularization and intraretinal vascular changes [57]. Peripheral avascularity is also seen in FEVR, Coats disease, CXLRS, and incontinentia pigmenti, although the relationship between disease activity and VEGF produced by an avascular peripheral retina is less clear in these conditions. Areas of avascularity may escape detection on clinical examination when they are not bounded clearly by a demarcation line or a ridge. FEVR, in particular, is characterized by crescents of peripheral retinal nonperfusion, which may be difficult to identify without angiography [24]. In Coats disease, patches of nonperfused retina may be seen anteriorly or adjacent to characteristic vascular changes. In CXLRS, retinal nonperfusion may occasionally be seen within areas of retinoschisis. The standard of care for the treatment of ROP does not require fluorescein angiography, but angiography may be appropriate when an inadequate clinical response is seen after standard-of-care peripheral laser ablation, as angiography may identify islands of retinal nonperfusion posterior to the clinically identifiable ridge, which usually demarcates vascular and avascular retina. Fluorescein angiography is also invaluable in the detection of posterior avascular islands in FEVR, Coats disease, and incontinentia pigmenti (Fig. 2.5). The treating surgeon may then apply ablative laser to the avascular retina, although the efficacy of such treatment remains to be confirmed in a large case series or in a prospective study [56]. Broad areas of clinically inapparent avascular retina may also be present in conditions not usually thought to be associated with retinal nonperfusion. Shaken baby syndrome is characterized clinically by intraretinal hemorrhages extending to the ora serrata and occasionally preretinal or subhyaloid hemorrhages [1, 32]. Retinal nonperfusion is often apparent on fluorescein angiography [13]. The implications and management of such nonperfusion are unclear, but these findings likely warrant close follow-up for signs of neovascular sequelae secondary to ischemia.