21 Retinal detachment and proliferative vitreoretinopathy

INTRODUCTION

Proliferative vitreoretinopathy (PVR) is a disease entity related to a number of intraocular diseases, including retinal detachment (RD). Several studies have confirmed the hypothesis that PVR occurs as a reparative process induced by retinal breaks and excessive inflammatory reaction. A survey of recently published series suggested that the frequency of PVR remains largely unchanged in primary RD, with the incidence ranging from 5.1 to 11.7%.1 PVR is the most common cause of failed repair of rhegmatogenous RD and risk factors for PVR are related to several, well-known pre-, intra-, and postoperative clinical situations. Currently, surgery such as pneumatic retinopexy, scleral buckling, and pars plana vitrectomy (PPV) is the mainstream therapeutic modality for RD and PVR. The goal of surgery is to create chorioretinal adhesion around all the retinal breaks and to relive all the tractional force. Single-operation reattachment rates were 73% for pneumatic retinopexy and 82% for scleral buckling after 6 months, and multipleoperation reattachment rates at 2 years were 99% for pneumatic retinopexy and 98% for scleral buckling for RD. Surgical success rates for PVR have improved as techniques and instruments of vitrectomy evolved. The introduction of ancillary techniques such as longer-acting gases and long-term vitreous substitutes like silicone oil elevated the success rate from 35–40% to approximately 60–75% at 6 months. Despite these advances, more than one-fourth of initially successful cases results in redetachment due to recurrent retinal traction. Furthermore, visual results are less satisfactory and only 40–80% of cases with anatomic success achieve ambulatory vision. As a result, PVR remains a difficult problem to manage and continuing efforts have been made to develop other forms of therapy to inhibit the pathologic response causing traction. Recent efforts have been directed toward the chemical inhibition of cellular proliferation and membrane contraction in PVR.

RD occurs at a rate of 5–16 per 1000 cases following cataract surgery, and this comprises approximately 30–40% of all reported RD.4 The cumulative probability ratio of RD at 20 years after extracapsular cataract extraction or phacoemulsification is reported to be 1.58%, which is four times higher than for patients not undergoing cataract extraction.5 The risk factors associated with RD in cataract removal are accidental posterior capsule rupture at the time of surgery, young age, increased axial length, a deep anterior chamber, RD in the fellow eye, and male gender.6,7 While the incidence of RD after clear lens extraction in myopic eyes rises to 8.1%, the incidence of RD decreases to 2.7% with the introduction of small incision coaxial phacoemulsification.8,9

Approximately 10–20% of RD is associated with direct ocular trauma. Traumatic detachments are more common in younger people. Although no studies have estimated the incidence of RD in contact sports, certain sports (e.g., boxing and bungee jumping) are associated with an increased risk of RD. There are also a few reports that Nd : YAG laser capsulotomy10,11 is associated with an increased risk of RD.

As for racial difference in the incidence of RD in pediatrics, while structural abnormalities (56%), previous surgery (51%), trauma (36%), and uveitis (15%) were the main risk factors for RD in USA,12 high myopia (38%), trauma (31%), structural abnormalities (17%), and previous surgery (5%) were the main risk factors in Asia.13

INCIDENCE OF PROLIFERATIVE

VITREORETINOPATHY

Published series through the 1990s to early 2000 suggest that the frequency of PVR remains largely unchanged in primary RD, with the incidence ranging from 5.1 to 11.7%.

In normal eyes, RD occurs at a rate of approximately 5 per 100 000 people per year in the USA, and the age-adjusted incidence of idiopathic RD is approximately 12.5 cases per 100000 per year, or about 28 000 cases per year.2,3

ETIOLOGY AND RISK FACTORS FOR RETINAL DETACHMENT

Rhegmatogenous RD develops with: (1) the existence of liquefied vitreous gel; (2) tractional force resulting in retinal breaks; and (3) the presence of a retinal break (Figure 21.1). The most common worldwide etiological factors associated with RD are myopia, cataract removal, and trauma. Approximately 40–50% of all patients with RD have myopia. RD related to myopia tends to occur in patients aged 25–45 years, while nonmyopia RD tends to occur in older individuals. Patients with high myopia (>6 D), which is more common in males than females, have a 5% lifetime risk of RD.

PVR is the result of growth and contraction of cellular membranes within the hyaloids, retina, and retinal surface.14 These membranes exert traction and may cause tractional RD that opens otherwise successfully treated retinal breaks, creating new retinal breaks, or promoting proliferation at the posterior vitreous base and anterior cortical vitreous. This in turn causes anteroperipheral traction on the retina with displacement of the peripheral retina toward the pars plana. Membrane contraction on the inner retina causes distortion and folding, resulting in starfolds at the inferior quadrant (Figure 21.2).

RISK FACTORS FOR PROLIFERATIVE VITREORETINOPATHY

Although PVR is the most common cause of failed repair of rhegmatogenous RD, risk factors for PVR are related to several, well-known pre-, intra-, and postoperative clinical situations. A number of factors can increase the risk of PVR, including the preoperative extent of

Vitreoretinopathy Proliferative• 21 chapterand Detachment Retinal

Pharmacotherapy to Amenable Diseases Retinal • 3 section

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Vitreoretinopathy Proliferative• 21 chapterand Detachment Retinal

A

B

Figure 21.5  Ability of perfluorocarbon liquids to reattach mechanically posterior retina in proliferative vitreoretinopathy. Epiretinal membranes cause folding and shortening of the retina in both anteroposterior and circumferential directions (A). After performing membranectomy on posterior region of the retina, perfluorocarbon liquid may be used to reattach the posterior retina and aid in removal of peripheral epiretinal membrane (B).

the majority of failures following RD surgery. Surgical procedures used to repair RDs associated with PVR include scleral buckling, vitrectomy, membrane peeling, relaxing retinotomies, the use of liquid perfluorocarbons, and internal tamponade with gas or silicone oil (Figure 21.5).31 In the early stages of PVR, buckling and encircling procedures may close all retinal breaks with release of circumferential traction caused by the vitreous base.17 Amoderately wide, broad silicone band (5–7 mm) extending from the ora serrata to the equator is required to reduce the vitreous traction.13 In addition, retinopexy with cryotherapy, diathermy, and photocoagulation can be used to treat definite retinal breaks, thus minimizing further RPE cell dispersion, postoperative inflammation, and breakdown of the blood–retinal barrier. While there is no standardized approach to PVR treatment, types 1 and 2 affecting fewer than two quadrants (classification system by the Silicone Oil study) can be successfully treated using buckling procedures.

PPV is indicated in cases with no definite retinal breaks with tractional membranes causing RD, or in cases where the retinal breaks cannot be sealed by scleral buckling alone.14 However, in complex PVR cases, it is necessary to perform a vitrectomy with membrane peeling and a gas or silicone oil tamponade.32 Moreover, a relaxing retinotomy and retinectomy may be required to attach the retina to the RPE in such complex cases.33 Once all traction is relieved, photocoagulation is

applied to the edges of the retinotomy site with the addition of longterm tamponades. Most severe cases involving advanced anterior PVR have used a posterior 360° retinotomy combined with an extensive peripheral retinectomy and silicone oil tamponade.34 However, the results have not been encouraging due to reproliferation causing recurrent macular detachment. Surgical means to reduce the risk of PVR include removal of vitreous collagen, which is the stratum to cell attachment, using wide-angle viewing systems and heavy liquids, and application of dyes which aim at a more thorough and less traumatic removal of vitreous and periretinal membranes.35 In addition, recent efforts have been directed toward the pharmacological inhibition of cellular proliferation and membrane contraction in PVR.

PROGNOSIS WITH THE VARIOUS TREATMENT OPTIONS

It appears that the surgical success rates for pneumatic retinopexy are either similar to or slightly lower than those for scleral buckling, and the risk of late redetachment is similar for pneumatic retinopexy and scleral buckling.30 In a 2-year follow-up study, single-operation reattachment rates were 73% for pneumatic retinopexy and 82% for scleral buckling after 6 months, and multiple-operation reattachment rates at 2 years were 99% for pneumatic retinopexy and 98% for scleral buckling.36

More recently, a few prospective randomized trials revealed that there was no statistically significant difference in single-operation success rates or visual outcomes when comparing primary vitrectomy with scleral buckling for the treatment of rhegmatogenous RD.37,38 However, faster foveal reattachment may be an advantage of PPV. In a nonrandomized series of 33 cases of macular-off RD, serial optical coherence tomography examinations showed no primary vitrectomy patients had subfoveal fluid while approximately one-third of scleral buckling patients had subfoveal fluid after the operation.39

Surgical success rates for PVR have improved as vitrectomy techniques and instruments have evolved. The introduction of ancillary techniques such as longer-acting gases and long-term vitreous substitutes like silicone oil have elevated the success rate from 35–40% to approximately 60–75% at 6 months.40,41 Despite these advances, more than 25% of initially successful cases result in redetachment due to recurrent retinal traction. Furthermore, visual results are less satisfactory and only 40–80% of cases with anatomic success achieve ambulatory (5/200 or better) vision.42 As a result, PVR remains a major problem, and continuing efforts have been made to develop other forms of therapy to inhibit the pathological response causing traction. Recent efforts have been directed towards chemical inhibition of cellular proliferation and membrane contraction for PVR.

ADJUNCTIVE THERAPIES

Although PVR is currently primarily managed surgically, ongoing efforts seek to identify adjuvant therapies that might inhibit PVR development. No matter how thoroughly vitrectomy is performed, it is virtually impossible to prevent some level of cell adhesion and pathological change. Control of the biological processes involved in proliferation and wound-healing would improve the success rate of surgery for primary RD and PVR.

Daunorubicin was the first adjunct agent to be studied in a randomized controlled trial for the management of PVR, and was found to reduce the number of reoperations within 1 year.43 Recent advances in the sustained release of daunomycin achieved by a single intravitreal application of liposome encapsulation44 may be very useful for future treatment strategies.

A randomized controlled trial in the UK reported that adjuvant 5-fluorouracil and heparin prevented PVR. In that study, the combination treatment resulted in a significant reduction in the rate of postoperative PVR development.45 However, subsequent studies failed to show any benefit of this combination treatment, and indeed one of the study results showed worse outcomes in macula-sparing RDs patients.46,47