Fig. 10.1
Schematic demonstrating the tractional vectors in advanced retinopathy of prematurity, including (i) intrinsic to the retina, (ii) ridge to lens, (iii) ridge to ridge, (iv) ridge to ciliary body, (v) ridge to retina, and (vi) persistent stalk tissue
Fig. 10.2
Schematic of progression of ROP (modified from [58]). In infants born prematurely, the retina is incompletely vascularized. Furthermore, premature infants are exposed to hyperoxic conditions, relative to the intrauterine environment, in order to overcome pulmonary insufficiency and prevent cerebral ischemia. This hyperoxia results in a suppression of the signals (including VEGF) required to complete vascularization of the retina (illustrated as Phase 1). The avascular retina then predisposes the eye to abnormal compensatory neovascularization when the oxygen levels are normalized (Phase 2). The disease progresses through stages that are defined by anatomic changes occurring at the border of the vascularized retina. In stage 0, arborization begins at the terminal vessels. This is followed by the development of a demarcation line in stage 1 (illustrated in gray), thickening of the tissue into a ridge in stage 2 (illustrated in red), and fibrovascular proliferation into the vitreous in stage 3. Left untreated, the fibrovascular proliferation can contract, resulting in traction on the underlying retina. These tractional forces can overpower the retinal pigment epithelium, resulting in a partial (stage 4), or complete (stage 5), detachment of the neurosensory retina. The mean postmenstrual age for the onset of each stage is illustrated in the timeline
Fig. 10.3
Surgical management of stage 5 ROP. a RetCam color photograph of presenting phenotype. Leukocoria is evident, with a poorly dilated pupil and pigment on the anterior lens capsule. The anterior chamber is shallow. b Intraoperative photograph showing retrolental plaque after removal of the crystalline lens. c After opening the anterior plaque, the center of the funnel detachment is identified. d Careful bimanual dissection of preretinal fibrosis with irrigating illuminated pick and intraocular forceps. e The dissection proceeds to the retinal surface, and then is extended using a blunt irrigating spatula. f Montage RetCam photograph 6-week postoperatively demonstrating attached posterior pole
A persistent hyaloidal vasculature is common in eyes of premature infants that progress to late stages of ROP, despite appropriate laser photocoagulation. Evidence from the oxygen-induced retinopathy (OIR) murine model, as well as human histological, biochemical, and clinical observations, provides insight into the pathophysiology of these cases. The development of the retinal vasculature in utero occurs under relatively hypoxic conditions, in which VEGF plays a critical role in driving developmental angiogenesis [8, 9]. The hyaloidal vasculature fills the developing vitreous with extensive connections to the developing retina. Systematic involution of these vessels occurs during development, beginning by 12-week gestation, and is completely regressed by 35–36-week gestation [10]. The main hyaloid trunk is the last element to undergo regression. Apoptosis is required for involution of the hyaloid vessels, and is influenced by low VEGF levels [11, 12] and elements of the Wnt signaling pathway [13, 14].
In the premature infant, exposure to high levels of VEGF driven by peripheral retinal ischemia results in reduced apoptosis of the hyaloid vessels [15]. Clinically, this is evident in a visible hyaloid structure, including the tunica vasculosa lentis, and rubeosis iridis. At the same time, an increase in plasmin enzyme from incompetent vessels results in partial liquefaction of the vitreous [16, 17]. Concomitant activation of TGFB1 contributes to excessive scar formation, causing the purse string effect wherein the retina is drawn toward the center of the eye. Ultimately, the eye succumbs to a cicatricial phase, and unchecked will present with retrolental fibroplasia [16, 18, 19].
Clinical Course
ROP is characterized by a relatively predictable timeline of progression. Initial manifestations of the disease are usually seen at approximately 32-week postmenstrual age (PMA), and the threshold for laser ablation is reached at a mean of 37-week PMA [20, 21]. Retinal detachment after appropriate laser ablation occurs at a mean of 41-week PMA [22]. The progression from an early stage 4A retinal detachment to stage 5 can occur quickly, often within a few weeks.
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, earlier intervention is advisable to minimize the extent of the detachment.
In contrast, surgery for stages 4B and 5 ROP 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-week PMA for vascular activity to decrease to intervene [23].
Management
The goal of ROP-related retinal detachment is to normalize anatomy in the effort to restore visual development and maximize visual potential. In stage 5 detachments, partial residual retinal detachment is common, but the goal is to remove the traction so as to reattach as much of the retina as possible and provide a stable anatomic result. To minimize the risk of creating an iatrogenic retinal tear, an anterior (translimbal) approach to lensectomy and vitrectomy is often preferable.
Various surgical approaches, including open-sky vitrectomy, two-port, and three-port vitrectomy have been utilized. Each approach has been reported with comparable success rates [24–28], leaving the preference of the surgeon dictating the technique of choice. All approaches share the goal of removing the fibrotic preretinal material without causing iatrogenic breaks. To do so successfully, the surgery requires bimanual dissection. Instruments that aid in permitting a two-hand dissection of preretinal fibrosis have been developed. In addition to the vitrector combined with intraocular forceps, key components include an irrigating spatula, irrigating illuminated pick, and vertical forceps (Fig. 10.4).
Fig. 10.4
Synergetics (O’Fallon, MO, USA) instrument design for use in pediatric vitreoretinal surgery. a Illustration of assembly of the combined 20/23 ga two ports infusing instrument canula system. Infusion is provided through two 20 ga canulas with embedded 23 ga instrument cannulas. The lengths of trocar blade, cannula shaft, and infusion shaft have been adjusted for smaller anatomy. b 23 ga Trese spatula with short platform, allowing canula compatible entry and removal. c 23 ga vertical forceps, with broad platform to allow dual function as dissection spatula and forceps. d 23 ga illuminated Capone/Rizzo Pick. Semi-malleable material allows pick to be bent to desired angle. e Large platform irrigating Trese Spatula. f Microserrated Snub Nosed Forceps. Blunt tip profile allows tissue to be engaged while preventing iatrogenic tears
In a two-port lensectomy–vitrectomy technique, infusion can be provided by with a 23-gauge bent butterfly needle. To avoid passing through the anteriorly drawn detached retina, entry into the eye is made immediately posterior to the limbus through the iris root, directed into the anterior lens. A two-port approach can be modified to three-port by placing an infusion canula inferotemporally immediately posterior to the limbus, to stabilize the anterior chamber and the unicameral anterior–posterior chamber subsequently. After aspiration of the crystalline lens with the vitrector, the lens capsule is removed using intraocular forceps.
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. Despite lenticuloretinal apposition in many stage 5 eyes, capsular material can generally be stripped away from the fibrous proliferation extending anteriorly from the retina without causing retinal breaks.
In contrast to the lens capsule, the retrolental fibrovascular plaque in stage 5 ROP is tightly adherent to the underlying retina. The plaque is opened centrally in an area free of adherent retina with a sharp instrument, such as the 23-gauge needle used for infusion, a microvitreoretinal (MVR) blade, or a 26-gauge needle on a Tb syringe can be used to initiate the dissection. Using two sharp instruments, one in each hand, a cross-action maneuver can create an opening in the plaque without causing traction on the peripheral retina. A lamellar dissection separating the plaque from the subjacent retina can then begin using an irrigating spatula and forceps, allowing a two-handed technique (see Fig. 10.3). Layers of preretinal fibrosis and vitreous are carefully removed to safely dissect down to the retinal surface. During the anterior dissection, the operating microscope is sufficient to provide illumination. As the dissection proceeds posteriorly, the illumination can be provided by either endoillumination (light pipe or illuminated pick), or by external illumination with the light pipe directed by an assistant through a hand-held irrigating contact lens.
Viscoelastic substances, such as healon, can also be used to aid in dissection. Injection of viscoelastic can be effective in separating tight retinal folds and proliferative tissue. In addition, viscoelastic is effective at stabilizes the highly mobile retinal surface, allowing dissection while preventing iatrogenic breaks. Care must be taken while injecting viscoelastic to avoid causing peripheral dialysis or posterior tears. At the conclusion of the dissection, a partial air–healon exchange is typically performed and sclerotomies are sutured.
Enzymatic Targeting of the Vitreoretinal Junction
A subset of advanced ROP surgeries fails due to incomplete removal of the posterior hyaloid. 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 [29]. 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 the vitreoretinal adhesions, mediated by laminin and fibronectin, and facilitate posterior vitreous detachment [30–32]. When additional surgeries are needed that require successful peeling of preretinal membranes or the posterior hyaloid to achieve primary surgical goals, the use of plasmin enzyme or ocriplasmin may facilitate the removal of such membranes and reduce the risk of creating an iatrogenic retinal breaks (for review, see [33]). 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 is initiated approximately 30 min thereafter.
Outcomes
Retinal detachments in children who are properly screened and appropriately ablated are fortunately rare. However, a retinal detachment in infancy can profoundly impact visual development. Even in eyes with minor degrees of detachment, the outcomes can be poor [22, 34, 35]. As one might expect, the success rates and the visual outcomes are worse with more advanced stages of disease. Successful reattachment has been reported in 74–91% of stage 4A detachments [36–41], 62–92% of stage 4B detachments [37, 39, 41–44], and 22–48% of stage 5 detachments [24, 27, 45–47]. Visual outcomes in successful repair of stage 4A detachment can be expected to be 20/80 or better [37, 48, 49], ambulatory vision following stage 4B repair [44], and form vision following stage 5 repair [25, 50]. A summary of the outcomes of the following stage 5 repairs is shown in Table 10.1.
Table 10.1
Summary of the outcomes of the following stage 5 repair
Study | N (Eyes) | Surgery | % Anatomic success* | VA outcomes (%) |
|---|---|---|---|---|
Trese 1986 [24] | 85 | LV | 48.2 | BTL (63.4)+++ F/F (43.9) Grasping behavior (37.5) Recognize shapes (15) |
Hirose 1992 [59] | 524 | OSV | 39.2 | NA |
Hirose 1993 [28] | 55 | OSV | 100** | 20/100-20/400 (7.3) 20/400-20/800 (20) 20/800-20/1600 (30.9) ≤20/3200 (41.8) LP (9.1) |
Choi 1994 [60] | 38 | LV | 29 | F/F (18.4) LP (39.5) NLP (42.1) |
Mintz-Hittner 1997 [25] | 45 | SB with subsequent LV | 26.4 | 20/80 (11.1) 20/200 (11.1) 20/400 (22.2) 20/800 (33.3) 20/1600 (22.2) |
Hartnett 2003 [54] | 6 | NA | 50 | Avg TAC score 12 (attached) Avg TAC score 6 (detached) Avg LPP score 5 (attached) Avg LPP score 2 (detached) |
Cusick 2006 [27] | 608 | LV (94%)*** | 33 | >20/200 (2) 5/200-20/200 (2) HM (10) LP (59) NLP (26) |
Lakhanpal 2006 [61] | 33 | LSV | 45.5 | NA |
Lakhanpal 2006 [46] | 21 | LV | 28.6 | NA |
Wu 2008 [62] | 80 | Plasmin-assisted LV (83.8%)+ | 68.8 | Pattern vision (7.5) F/F (3.8) LP (70) NLP (13.8) VEP positive (5) |
Kondo 2009 [63] | 82 | LV | 81.7%++ | >20/200 (1.8) 20/200-20/2000 (11.1) FWM (14.8) LP or HM (35.2) NLP or ND (37.0) |
Shah 2009 [64] | 14 | LV | 14.3 | LP (21.4) NLP (78.6) |
Total | 1591 | 38.3# |
OSV (open-sky vitrectomy), LV (lensectomy–vitrectomy), V (vitrectomy), LSV (lens-sparing vitrectomy), SB (scleral buckle), TAC (teller acuity cards), LPP (light perception/projection) scale, F/F (fix and follow), FWM (following with or without nystagmus), ND (not determined attributable to mental disability and/or amblyopic status), NA (not available)
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