Machemer and coworkers first performed pars plana vitrectomy for the management of complications of diabetic retinopathy in 1970.^6,7 Initially, diabetic vitrectomy was performed primarily to remove nonclearing vitreous hemorrhage. In 1975, Machemer described using vitrectomy techniques to remove preretinal proliferative membranes.⁸ Since then, indications for diabetic vitrectomy have increased to include the following: nonclearing vitreous hemorrhage, tractional retinal detachment, combined tractional and rhegmatogenous retinal detachment, progressive fibrovascular proliferation, and macular edema associated with posterior hyaloidal traction (Table 1). This increase in indications for diabetic vitrectomy is primarily the result of significant advances in vitrectomy instrumentation and surgical techniques. However, despite advances in our understanding of the pathophysiologic mechanisms of diabetic retinopathy and improvements in instrumentation and surgical techniques, patients with complications of diabetes mellitus remain among the most difficult patients to manage.

TABLE 1. Indications for Diabetic Vitrectomy

  Nonclearing vitreous hemorrhage
  Traction retinal detachment involving the macula
  Combined tractional-rhegmatogenous retinal detachment
  Progressive active fibrovascular proliferation
  Macular edema associated with posterior hyaloidal traction
  Dense premacular hemorrhage
  Dense vitreous hemorrhage in the presence of anterior segment neovascularization

ANESTHESIA

Vitrectomy for complications of diabetic retinopathy can be performed with the patient under local or general anesthesia. The choice of anesthesia depends on the surgeon's and patient's preferences, the estimated duration of the procedure, and any systemic conditions that might place the patient at increased risk with general anesthesia. Local anesthesia offers the advantage of minimal disruption of the patient's diabetic management but may not be appropriate for long procedures or for patients who cannot remain immobile.

REMOVAL OF VITREOUS HEMORRHAGE

If the vitreous hemorrhage is dense, preoperative ultrasonography is useful to delineate areas of retinal detachment and to ascertain whether a posterior vitreous detachment is present. After a core vitrectomy is performed, an opening in the posterior hyaloid is made with the vitrectomy probe. Subhyaloid hemorrhage then is aspirated with the probe or with a soft-tipped extrusion needle. Next, the posterior hyaloid and peripheral vitreous are removed. If no posterior vitreous detachment is present, one can be created by engaging the posterior vitreous over the optic disk or in the posterior pole adjacent to an area of proliferation, or the posterior hyaloid can be incised over an area of subhyaloid hemorrhage.

MEMBRANE DISSECTION

Techniques for removal of epiretinal fibrovascular membranes have evolved over the past 10 years. Three techniques, or combinations thereof, are commonly used, including (1) segmentation, (2) delamination, and (3) “en bloc” dissection.

SEGMENTATION

Segmentation was the earliest method used to release retinal traction caused by preretinal fibrovascular proliferation. A core vitrectomy is first performed (Fig. 1A). Anteroposterior traction then is released by circumferentially cutting the posterior vitreous surface around the area of epiretinal proliferation (see Fig. 1B). After the anteroposterior traction has been released and the formed vitreous has been removed, the posterior vitreous surface is cut between epicenters of fibrovascular adhesion, leaving islands of fibrovascular tissue. It also may be necessary to excise bridges of fibrovascular tissue connecting epicenters, using the vitrectomy probe or intraocular scissors (see Fig. 1C). Bleeding often is a problem during segmentation because the neovascular tissue is cut far away from its origin within the retina. Intraocular diathermy often is required to control bleeding from stumps of severed fibrovascular membranes. Raising the intraocular pressure also can be used temporarily to control intraoperative hemorrhage. Finally, panretinal endophotocoagulation is applied (see Fig. 1D).

DELAMINATION

Delamination begins similarly to segmentation with the removal of the partially detached posterior vitreous surface between the vitreous base and the edge of the fibrovascular adhesions. Using bimanual techniques, from anterior to posterior, the edge of the fibrovascular membrane is reflected using either a lighted pick, lighted forceps, the light pipe, or a tissue manipulator (Fig. 2A). This allows the epicenters of adhesion between the retina and the fibrovascular membrane to be visualized. These epicenters then are amputated at the retinal surface using horizontal scissors, membrane peeling cutter scissors, or a diamond blade (see Fig. 2B). This technique is continued until all of the fibrovascular tissue has been removed up to the optic nerve head. The membrane then can be grasped with a forceps and gently avulsed (see Fig. 2C). Unlike segmentation, after membrane dissection using delamination technique, minimal or no epiretinal tissue remains on the retinal surface (see Fig. 2D). In cases with broad areas of severe vitreoretinal adhesion, a combination of delamination and segmentation may be necessary.

“EN BLOC” VITRECTOMY AND MEMBRANE EXCISION

The en bloc technique uses the anteroposterior traction of the vitreous to elevate the edge of the fibrovascular membrane, thus serving as a “third hand.” Removal of the formed vitreous is delayed until the end of the membrane removal. Initially, the vitrectomy cutter is used to create a tunnel through the formed vitreous from the sclerotomy site to an area of vitreoretinal separation (Fig. 3A). Any subhyaloid blood then is removed through this opening. The remaining posterior vitreous surface is left attached and assists in visualizing epicenters of adhesion between fibrovascular tissue and the retina (see Fig. 3B). An illuminated pick may be used to further elevate the fibrovascular tissue, and horizontal scissors are used to amputate epicenters of fibrovascular vitreoretinal adhesion (see Fig. 3C). Hemorrhage may occur when these epicenters are cut, but since the vessels are cut close to their origin, the bleeding usually is minimal and stops spontaneously. After the posterior vitreous surface and the entire fibrovascular membrane are freed from the retina, they are removed using the vitrectomy probe (see Fig. 3D). The main disadvantage of this technique is an increased risk of iatrogenic peripheral retinal breaks caused by traction at the vitreous base, which may occur in up to 35% of cases.¹³ Should peripheral retinal breaks occur, they are treated with laser photocoagulation and a longacting intraocular gas tamponade, with or without scleral buckling, depending on break location and surgeon preference.

MEMBRANE AVULSION FROM THE OPTIC NERVE

Using the delamination or en bloc technique, the fibrovascular membrane can be dissected from the retina up to the optic nerve head. At this point, the membrane can be avulsed from the optic nerve. Alternatively, the membrane can be trimmed close to the nerve and the remaining stump of tissue treated with diathermy. Avulsing the tissue assures that no traction persists. Bleeding often occurs when the tissue is avulsed, but usually it is limited and ceases spontaneously.¹⁴ Disadvantages of leaving tissue attached to the optic nerve include the possibility of persistent or recurrent retinal traction or inadvertent trauma to the optic nerve from diathermy.

NONCLEARING VITREOUS HEMORRHAGE

Nonclearing vitreous hemorrhage is the earliest indication for vitrectomy in diabetic patients and generally is the least complex. Although its prevalence has decreased with extensive use of panretinal photocoagulation, it remains a common indication for diabetic vitrectomy.¹⁵ In the Diabetic Retinopathy Vitrectomy Study, eyes with severe, nonclearing vitreous hemorrhage of 1 to 6 months' duration were randomized to immediate vitrectomy versus deferral of vitrectomy for 1 year.¹⁶ The percentage of patients with visual acuity of 10/20 or better was higher in the early vitrectomy group than in the deferral group throughout the 4-year follow-up period. However, until the 18-month follow-up visit, the early vitrectomy group had a higher percentage of eyes with loss of light perception. This was undoubtedly related in part to the unavailability of argon laser endophotocoagulation. An increased chance of obtaining good vision was clearly observed for early vitrectomy in patients with type I diabetes. However, this finding was not seen in patients with type II diabetes. The main advantages of early vitrectomy include a higher likelihood of recovering useful vision and earlier recovery of vision in successful cases. For individual patients, the exact timing of vitrectomy for nonclearing vitreous hemorrhage must take into account not only the duration of hemorrhage, but also the type and duration of diabetes, the severity of retinopathy (if known), and the status of the fellow eye.

Thompson and colleagues evaluated the results of 353 vitrectomies for nonclearing diabetic vitreous hemorrhage.¹⁷ Eighty-one percent of eyes had improved visual acuity on final examination. The percentage of eyes with a final visual acuity of 20/100 or better was 48%, and the percentage with a final visual acuity of 5/200 or better was 81%. Preoperative factors associated with a favorable visual prognosis included the following: preoperative visual acuity of 5/200 or better, absence of iris neovascularization or neovascular glaucoma, minimal cataract, and panretinal photocoagulation of at least one fourth of the fundus.

MACULAR TRACTION RETINAL DETACHMENT

The pathogenesis of diabetic traction retinal detachment involves interaction between the posterior hyaloid surface, preretinal fibrovascular proliferation, and the retina. Epiretinal fibrovascular tissue grows along the posterior surface of the vitreous gel. As the fibrovascular tissue contracts, the posterior hyaloid becomes taut and partially separates from the retina. Anteroposterior traction on the remaining areas of vitreoretinal attachment causes tractional retinal detachment. Traction retinal detachments are separated into those where the macula is detached and those where the traction detachment does not involve the macula (Fig. 4). Charles and Flinn studied the natural history of diabetic extramacular traction retinal detachment.¹⁸ They found a progression to macular detachment in only 13.8% of eyes at 1-year follow-up. Because most patients with extramacular traction retinal detachments do not progress to involve the macula, vitrectomy is indicated only for patients with traction macular detachment in the absence of significant macular heterotopia or vitreous hemorrhage. In patients with traction macular detachment, surgery should not be deferred for an extended period of time because retinal vascular changes may cause irreversible macular damage, reducing the potential for visual recovery.¹⁹ The results of vitrectomy for 360 eyes with diabetic traction retinal detachment of the macula were evaluated.²⁰ Fifty-nine percent of eyes had improved visual acuity on final examination. The percentage of eyes with final visual acuity of 20/100 or better was 36%, and the percentage with a final visual acuity 5/200 or better was 72%. Preoperative factors associated with a favorable visual prognosis included the following: visual acuity of 5/200 or better, absence of iris neovascularization, minimal cataract, mild or no vitreous hemorrhage, panretinal photocoagulation of at least one fourth of the retina, and absence of severe retinal neovascular proliferation. Intraoperative factors associated with a worse visual prognosis included lensectomy, iatrogenic retinal breaks, and use of intraocular gas tamponade.

COMBINED TRACTION-RHEGMATOGENOUS RETINAL DETACHMENT

Vitreous traction and contraction of proliferative tissue can produce retinal tears, leading to combined traction-rhegmatogenous detachments. Unlike purely tractional detachments, extramacular rhegmatogenous detachments frequently progress to involve the macula, leading to rapid and severe visual loss. Thus, surgical repair is indicated in combined detachments, whether or not the macula is involved. Often, the retinal breaks are located posterior to the equator, adjacent to areas of fibrovascular proliferation that are under severe vitreoretinal traction. Therefore, this condition is difficult to treat by conventional scleral buckling methods, whereas vitrectomy (with or without scleral buckling) is effective in treating this condition (Fig. 5). Intraocular long-acting gas tamponade is required to treat these detachments. Combined traction-rhegmatogenous detachments have a lower success rate than pure tractional detachments or nonclearing vitreous hemorrhage. In an analysis of 172 eyes that underwent vitrectomy for combined traction-rhegmatogenous diabetic retinal detachment, 48% had an improved visual acuity on final examination.²¹ A final visual acuity of 20/100 or better was achieved in only 25% of eyes, and a final visual acuity of 5/200 was achieved in 56%. Visual loss progressed to no light perception in 23% (compared with 19% for macular traction detachment and 6% for nonclearing vitreous hemorrhage). Preoperative factors associated with a favorable visual prognosis included visual acuity of 5/200 or better, absence of iris neovascularization, and absence of retinal detachment involving the macula. The only intraoperative factor found to be associated with a favorable visual prognosis was the absence of iatrogenic retinal breaks.

PROGRESSIVE ACTIVE FIBROVASCULAR PROLIFERATION

In most patients with PDR, panretinal photocoagulation induces regression of retinal and optic disc neovascularization. In some patients, however, fibrovascular proliferation progresses despite full panretinal photocoagulation treatment. The importance of vitreoretinal contact in the development of neovascular proliferation has been recognized since 1965.²² When the vitreous gel is removed, the proliferative process tends to stabilize. It is rare for neovascularization of the disc or posterior fundus to occur in eyes that have undergone complete vitrectomy. Since the natural history for eyes with severe fibrovascular proliferation is poor, the Diabetic Retinopathy Vitrectomy Study evaluated the role of vitrectomy in eyes with extensive, active neovascular or fibrovascular proliferation and useful vision (better than 10/200).²³ Forty-four percent of eyes in the early vitrectomy group achieved a visual acuity of 10/20 or better, compared with 28% for the conventional management group. The greatest benefit was observed for eyes with severe fibrous proliferation and moderately severe neovascularization. Thus, for eyes with active, progressive, fibrovascular proliferation despite maximal panretinal photocoagulation, vitrectomy should be considered. However, vitrectomy does not take the place of panretinal photocoagulation and should be reserved only for eyes where laser cannot be applied or where laser has failed to stabilize the neovascular proliferation.

MACULAR EDEMA ASSOCIATED WITH POSTERIOR HYALOIDAL TRACTION

Although the ETDRS showed that focal macular photocoagulation is beneficial in the treatment of clinically significant diabetic macular edema, it has been observed that some patients with diabetic macular edema and a taut, thickened posterior hyaloid do not respond to macular photocoagulation. It has been hypothesized that vitreous traction may cause or exacerbate macular edema in these patients. Lewis and coauthors report the results of pars plana vitrectomy with separation of the posterior hyaloid in 10 eyes with diabetic macular edema and traction associated with a thickened and taut premacular posterior hyaloid.²⁴ Preoperative fluorescein angiography showed a deep, diffuse pattern of leakage in the macula (Fig. 6). Nine of 10 eyes had previous macular photocoagulation, and only 1 of these eyes responded with a temporary decrease in macular edema. Postoperatively, vision improved in nine eyes, and macular edema resolved in eight eyes. Postoperative complications included vitreous hemorrhage, rhegmatogenous retinal detachment, cataract formation, and mild epimacular membrane (each occurring in one eye). Other studies also report visual improvement after vitrectomy and posterior hyaloid separation in such patients.²⁵ Tachi and Ogino report the results of pars plana vitrectomy with separation of the posterior hyaloid in 58 eyes with diffuse diabetic macular edema without posterior vitreous detachment.²⁶ These patients differed from those in prior reports in that they did not manifest a taut, thickened posterior hyaloid, and thus it is not clear whether the posterior hyaloid was responsible for the macular edema. Although these patients showed an improvement in macular edema and visual acuity, this study was not controlled and included only a few patients. Thus, it is reasonable to consider vitrectomy and posterior hyaloid separation in patients with diffuse diabetic macular edema associated with a taut and thickened posterior hyaloid, whereas the long-term efficacy of such surgery in patients with diabetic macular edema without vitreoretinal interface abnormalities has not been conclusively proven.

DENSE PREMACULAR HEMORRHAGE

Whereas most subhyaloid hemorrhages clear spontaneously, some eyes with dense premacular hemorrhage develop premacular fibrosis or traction macular detachment. Some authors suggest that vitrectomy in such eyes may improve visual prognosis. This has not been conclusively proven in prospective trials. Eventually, data from the Diabetic Retinopathy Vitrectomy Study should become available regarding such patients, hopefully clarifying the indications and timing of vitrectomy for eyes with premacular hemorrhages.

DENSE VITREOUS HEMORRHAGE IN THE PRESENCE OF IRIS NEOVASCULARIZATION

In patients with potential for useful vision who present with dense vitreous hemorrhage and iris neovascularization or neovascular glaucoma, delaying vitrectomy to wait for possible clearance of the hemorrhage is not a viable option. These eyes require prompt panretinal photocoagulation to treat the anterior segment neovascularization. Vitrectomy allows clearance of media opacity so that panretinal endophotocoagulation can be applied.

TABLE 2. Complications of Diabetic Vitrectomy

  Intraoperative Complications
  Corneal edema
  Miosis
  Lens opacification
  Intraocular hemorrhage
  Iatragenic retinal breaks or detachment
  Postoperative Complications
  Cataract
  Recurrent vitreous hemorrhage
  Glaucoma
  Anterior hyaloidal fibrovascular proliferation
  Retinal detachment
  Intraocular fibrin syndrome
  Endophthalmitis

INTRAOPERATIVE COMPLICATIONS

Corneal Edema

The most common intraoperative complication during diabetic vitrectomy is corneal epithelial haze. Abnormalities of the corneal epithelial basement membrane and reduced epithelial adherence in patients with diabetes increase epithelial edema during surgery. The resulting epithelial haze can limit adequate visualization of retinal or vitreous details. The amount of epithelial haze is related to the length of the procedure, intraocular pressure, and corneal exposure. To reduce the incidence of corneal haze, the length of the procedure and duration of elevated intraocular pressure should be kept to a minimum. Additionally, the cornea should be continuously coated with irrigating solution or viscoelastic to prevent drying and exposure. If epithelial haze becomes too severe to achieve the surgical objectives, corneal epithelial debridement often greatly improves visibility. However, corneal epithelial defects heal slowly in diabetic patients, and diabetics are at particularly high risk of developing chronic, nonhealing corneal epithelial defects. Thus, epithelial debridement should be avoided if possible. Folds in Descemet's membrane also may increase glare and reduce corneal transparency. This is particularly a problem during air-fluid exchange. These folds may occur with hypotony, in which case corneal clarity may be improved by elevating the intraocular pressure. Coating the endothelial surface with a thin layer of viscoelastic also can temporarily improve corneal clarity.

Miosis

Pupillary constriction can severely limit visualization during vitrectomy. Some diabetic patients, particularly those with rubeosis irides, do not dilate well. Miosis also may occur intraoperatively because of direct iris trauma or prolonged hypotony. Topical nonsteroidal antiinflammatory agents have been shown to prolong intraoperative mydriasis, and some surgeons include application of these drops in their preoperative routine.^27,28 Intraoperative miosis sometimes can be improved by applying additional dilating drops. The use of intraocular mydriatic agents such as dilute epinephrine is discouraged because of concerns about retinal vascular compromise or toxicity. When pharmacologic agents do not provide adequate dilation, flexible iris hooks usually are successful in achieving satisfactory dilation. With the use of iris hooks, sphincterotomies or iridectomies rarely are necessary. Additionally, wide-angle panoramic viewing systems allow improved retinal visualization through small pupils compared with traditional direct viewing systems. Thus, the need for wide pupillary dilation has been reduced in many cases.

Lens Opacification

Decreased lens clarity may occur during diabetic vitrectomy because of direct trauma from intraocular instruments, lengthy surgery, sustained elevated intraocular pressure, or increased infusion fluid volumes.^29,30 Feather-like opacities of the posterior capsule often occur with lengthy surgery or when the patient's blood glucose is significantly higher than that in the infusion fluid. Adding supplemental glucose to the infusion fluid can reduce the occurrence of these opacities.²⁹ These opacities usually resolve spontaneously several days after surgery and do not require intervention unless they significantly limit surgical visibility. Opacities from instrument trauma often progress rapidly, severely limiting surgical or postoperative visibility. When such lens changes are observed to progress intraoperatively, lens removal usually is warranted. Retrolental hemorrhage sometimes limits surgical visibility and, if not removed, can lead to postoperative shakeout hemorrhage. It is desirable to remove this hemorrhage if possible. However, if this cannot be accomplished without significant risk of lens trauma and the hemorrhage is not in the visual axis, removal should not be attempted.

Intraocular Hemorrhage

Bleeding from cut edges of fibrovascular tissue is common during membrane dissection in diabetic vitrectomy. Usually, the bleeding is mild and self-limited or can be halted using bipolar diathermy. If the bleeding is more profuse, making localization of the bleeding source difficult, the intraocular pressure can be raised to tamponade the bleeding and allow the source to be treated with diathermy. Another source of intraocular hemorrhage is from iris vessels, particularly in patients with iris neovascularization. This also generally is self-limited or can be treated in a similar fashion. Extensive preoperative panretinal photocoagulation helps to prevent intraocular hemorrhage by reducing the extent and caliber of neovascular vessels. Some authors advocate infusing thrombin to reduce intraoperative bleeding, but this may result in a sterile hypopyon and generally is not used.³¹ Rarely, uncontrollable bleeding may occur. This is more likely to occur in patients with poorly controlled diabetes or severe hypertension. When the measures discussed earlier are unsuccessful in halting brisk bleeding, the surgery may be terminated and the patient brought back to surgery for completion after a delay of 1 to 2 days.

Iatrogenic Retinal Breaks

Iatrogenic retinal breaks continue to be a serious complication of vitreous surgery in diabetics. In a series of 179 eyes of patients undergoing vitrectomy for complications of diabetic retinopathy, iatrogenic retinal breaks occurred in 20%.³² Thirty-four percent of the breaks were located anterior to the equator, and 66% were located posterior. Of the retinal tears that occurred anterior to the equator, 87% were located in the meridian of one of the sclerotomies. This indicates that anterior breaks are likely to be associated with repeated insertion and removal of vitrectomy instruments, and thus the risk of this complication can be minimized by limiting the frequency of instrument insertion. At the end of the procedure, before closing the sclerotomies, a thorough examination of the retinal periphery should be performed with scleral depression and indirect ophthalmoscopic study to detect any retinal breaks that may have occurred. If air-fluid exchange is planned, inspection of the retinal periphery should be performed beforehand because air or gas may close retinal breaks, making them difficult to detect. If an anterior break or a large posterior break causes intraoperative bullous retinal detachment or extension of preexisting detachment, liquid perfluorocarbon can be used to stabilize the retina and drain the subretinal fluid through the break.

POSTOPERATIVE COMPLICATIONS

Cataract

Cataract formation is the most common postoperative complication of diabetic vitrectomy. Early cataract formation usually results from surgical trauma or prolonged lens contact with intraocular gas. Rupture of the lens capsule results in lens swelling and opacification and may result in angle-closure glaucoma, requiring lens removal. Late cataract formation or progression of a preexisting cataract is common after vitreous surgery, particularly if long-acting intraocular gas tamponade is used.

Recurrent Vitreous Hemorrhage

Postoperative hemorrhages have been reported in up to 50% of eyes after diabetic vitrectomy.³³ These occur most often in the early postoperative period and are a result of residual hemorrhage or bleeding from cut edges of fibrovascular tissue dissected during the operation. Sometimes, however, vitreous hemorrhage may occur later because of fibrovascular ingrowth from the sclerotomy incisions or anterior hyaloidal fibrovascular proliferation (AHFP) (discussed later). Residual hemorrhage from dissected fibrovascular tissue usually resolves without further intervention or complication, although it may take several months. This may present significant morbidity in a monocular patient. Additionally, persistent postoperative hemorrhage is undesirable, since it contains chemotactic and mitogenic factors and has been shown to stimulate fibrous ingrowth and epiretinal membrane formation.^34,35

Hemorrhage from fibrovascular ingrowth begins several months after vitrectomy, although it can be variable and may occur several years later.^33,36 A useful finding in making the diagnosis of fibrovascular ingrowth is the presence of dilated subconjunctival blood vessels entering the sclerotomy sites. The course of fibrous ingrowth can be variable. Although most cases regress spontaneously, some require reoperation with radical anterior vitrectomy, as well as diathermy or cryotherapy to the sclerotomy sites. Silicone oil also may be useful in patients with recurrent hemorrhaging.³⁷ Despite these efforts, some patients will progress to retinal and ciliary body detachment and phthisis bulbi.

Glaucoma

Several mechanisms may be responsible for postvitrectomy intraocular pressure elevation. A transient pressure elevation commonly is found on the first postoperative day that can be managed with glaucoma medications or by paracentesis if necessary. Sustained elevation of intraocular pressure may result from red cells or cellular debris obstructing the trabecular meshwork. Preexisting primary open-angle glaucoma also can be exacerbated after vitreous surgery. Acceptable pressure levels usually can be maintained with topical glaucoma medications or oral carbonic-anhydrase inhibitors. The amount and duration of intraocular pressure elevation tolerated by a diabetic often is lower than in healthy patients because of compromised circulation. Acceptable pressure levels must be determined on an individual basis, although transient pressures less than 30 mmHg rarely require treatment. Neovascularization of the iris and angle may cause open-angle or angle-closure glaucoma. Neovascular glaucoma once was a common complication after diabetic vitrectomy but now occurs less frequently because of a better understanding of its causes and because of preoperative and intraoperative panretinal photocoagulation. Aphakia, rhegmatogenous retinal detachment, and extensive retinal ischemia may be associated with neovascular glaucoma. An intact lens capsule and zonular system appear to provide a barrier to diffusion of vasoproliferative factors from the posterior segment anteriorly and may limit the incidence of anterior segment neovascularization. Repair of rhegmatogenous retinal detachments and adequate panretinal photocoagulation before, during, or after vitrectomy may avoid this complication.^38–40 Angle closure also can be caused by intraocular gas (particularly if the patient does not maintain proper head position postoperatively), as well as by choroidal hemorrhage or detachment.

Anterior Hyaloidal Fibrovascular Proliferation

Although uncommon, AHFP is a serious and potentially devastating complication of vitrectomy. Patients who develop AHFP tend to be young with extensive retinal neovascularization and severe retinal ischemia. It is characterized by extraretinal fibrovascular proliferation of the anterior retina that extends along the anterior hyaloid to the posterior surface of the lens. Contraction of this tissue can cause recurrent vitreous hemorrhages, retinal breaks and rhegmatogenous retinal detachments, or traction detachment of the peripheral retina or ciliary body leading to phthisis bulbi. After diabetic vitrectomy where the adjacent posterior vitreous surface has been removed, preexisting fibrovascular tissue usually regresses. However, in a phakic vitrectomy, the anterior hyaloid cannot be removed, and in cases with extensive retinal ischemia, preexisting or newly formed fibrovascular tissue may use the anterior vitreous as a support and extend anteriorly toward the lens. Encircling scleral buckles, which compromise choroidal blood flow, may contribute to the development of AHFP, although this has not been clearly demonstrated. Treatment of AHFP is difficult, often requiring scleral buckling, lensectomy, resection of anterior vitreous and fibrovascular membranes, and extensive laser or retinocryopexy. Silicone oil has been used successfully for earlier or less severe cases.

Retinal Detachment

Retinal detachment may occur after vitrectomy because of retinal breaks or traction that were preexisting and not noticed or were inadequately treated. Detachment also may occur because of the development of new breaks that develop in the early postoperative period. The detachment and small breaks may be difficult to diagnose because of media opacity or poorly dilating pupil. Ultrasound can be used to make the diagnosis in these situations. Traction detachments that do not include the macula can be observed and may not require further treatment. Posterior breaks without traction can be treated with an intraocular gas bubble, proper positioning, and laser photocoagulation. Detachments with peripheral breaks or posterior breaks with traction require repeat surgery, usually with scleral buckling and long-acting gas tamponade. Occasionally, patients may develop retinal detachment with intraocular fibrin and extensive periretinal proliferation. These detachments progress rapidly and can be difficult to treat.

Intraocular Fibrin Syndrome

Fibrin formation frequently is seen in the early postoperative period after vitrectomy. Diabetics are particularly susceptible to excessive fibrin membrane formation because of vascular endothelial incompetence. Severe fibrin formation is more common in eyes with rubeosis, after extensive neovascular proliferative tissue dissection, or when extensive panretinal endophotocoagulation has been performed. Fibrin membranes may form on intraocular surfaces, including the iris and lens. Usually fibrin formation is mild or can be treated with aggressive topical steroids. Tissue plasminogen activator (tPA), a fibrinolytic enzyme, is effective in dissolving fibrin membranes.⁴¹ This should be reserved for severe cases and probably is useful only if fibrin membranes persist after the first postoperative week because of rapid fibrin reformation in the early postoperative period. Rarely, patients develop a fulminant fibrinous exudation with formation of transvitreal strands and rapid development of retinal detachment. In this syndrome, a gelatinous mass of tissue forms in the vitreous cavity, leading to retinal traction, detachment, and rubeosis. The typical patient with this syndrome is a young diabetic with poor blood glucose control and rapidly progressive diabetic retinopathy, nephropathy, and abnormalities in the coagulation cascade.^42,43 The prognosis in such severe cases is poor, and repeat vitrectomy often is not successful. Theoretically, preoperative and postoperative oral corticosteroid therapy might decrease the severity of fibrin reaction by blocking the release of arachidonic acid, but such efficacy has not been found clinically.

Endophthalmitis

Endophthalmitis after pars plana vitrectomy is rare. A study evaluating the 10-year incidence of postoperative endophthalmitis found an incidence of 0.046% after vitrectomy compared with an incidence of 0.093% for all surgeries.⁴⁴ The largest published series of patients with postvitrectomy endophthalmitis included 18 eyes and showed an incidence of 0.07%.⁴⁵ In this series, 34% of vitrectomies were performed on patients with diabetes mellitus, yet 61% of patients who developed endophthalmitis had diabetes. This suggests that endophthalmitis may be more common after vitrectomy in diabetics than in nondiabetics. Endophthalmitis after vitrectomy can be particularly devastating. Final visual outcome for patients with postvitrectomy endophthalmitis was no light perception in greater than half of cases published. Several possible reasons explain the worse prognosis for endophthalmitis after vitrectomy than after anterior segment surgery: First, antibiotic prophylaxis may be less effective when microorganisms are introduced directly into the vitreous cavity than in the anterior chamber because topical and subconjunctival antibiotics do not reach high concentrations in the vitreous cavity. Second, many patients have limited vision before vitrectomy and may not be aware of a sudden decrease in visual acuity postoperatively. Thus, they may not seek attention as promptly as patients undergoing cataract surgery. Third, eyes undergoing vitrectomy, particularly with panretinal photocoagulation, scleral buckling, or lengthy surgery, often manifest a large amount of sterile inflammation. Because of this, early signs of endophthalmitis may not be recognized and the diagnosis may be delayed, allowing time for more damage to occur. Finally, the pharmacokinetics of intraocular antibiotics differ between vitrectomized and nonvitrectomized eyes, which may make endophthalmitis more difficult to treat.⁴⁶ Visual prognosis in postvitrectomy endophthalmitis is strongly correlated with the type of infecting organism. Retention of ambulatory vision is rare unless the infecting organism has low virulence, such as coagulase-negative staphylococcus or P. acnes. The Endophthalmitis Vitrectomy Study⁴⁷ looked at treatment of eyes developing endophthalmitis after cataract surgery or placement of a secondary intraocular lens. The results of this study suggest that vitreous tap and intravitreal injection of antibiotics is preferable in less severe cases, and surgical clearing of vitreous debris with injection of intravitreal antibiotics should be performed in severe cases. Cases of endophthalmitis after vitrectomy were not evaluated in this study, so it is not clear if these guidelines apply in such eyes.

MANAGEMENT OF THE LENS

Several controversies persist regarding management of the lens during diabetic vitrectomy. These involve questions of when to remove the lens, what technique to use, and which intraocular lens, if any, should be placed. Lens removal is considered when a preexisting cataract is likely to significantly reduce the patient's visual acuity or preclude adequate visualization of the fundus for proper diagnosis or treatment. Lens removal also may be necessary when intraoperative lens opacity occurs. Additionally, lens removal sometimes is required to perform an adequate peripheral dissection of epiretinal proliferative tissue or hemorrhage. As discussed previously in this chapter, several steps can be taken to avoid intraoperative lens opacification. These include the following: avoiding direct instrument trauma to the lens, adding glucose to the infusion fluid, limiting the amount of time that intraocular pressure is elevated above normal, and limiting theduration of the procedure as much as possible. Sometimes, it can be difficult to decide whether to remove the lens. In 1983, Rice and associates showed that eyes undergoing vitrectomy for complications of diabetic retinopathy, where lensectomy was performed concurrently, were approximately three times more likely to develop iris neovascularization and approximately four times more likely to develop neovascular glaucoma than those where the lens was not removed.⁴⁸ Although these findings are important, notice that at the time endolaser photocoagulation was not available, and all of these patients were left aphakic with removal of the lens capsule. It is likely that the incidence of anterior segment neovascularization after vitrectomy with lens removal is lower when extracapsular cataract surgery techniques are used, particularly when zonular and capsular integrity is maintained and a posterior chamber intraocular lens is placed. Indeed, several series of combined pars plana vitrectomy with extracapsular cataract extraction or phacoemulsification and placement of a posterior chamber intraocular lens have since been published, with a low incidence of iris or angle neovascularization.^49–52 In most cases, if the lens is to be removed, it is best to retain the capsule and place a posterior chamber intraocular lens. In certain cases however, such as those where a severe fibrinous reaction or anterior hyaloidal fibrovascular proliferation is likely, it is advisable to remove the entire lens and capsule. When an intraocular lens is to be placed, a large optic lens should be used to improve visualization of the peripheral retina. Silicone lenses should be avoided because condensation can occur on the posterior lens surface during air-fluid exchange, greatly limiting visualization.^53–55 Silicone lenses also can pose a problem if silicone oil is used for tamponade because oil droplets can adhere strongly to the lens surface when the oil is removed.^56,57 Newer lenses made of acrylic polymers appear to be acceptable for use in patients with diabetic retinopathy, although experience with these lenses and vitrectomy in diabetics is limited. The method of lens removal depends on individual surgeon preference and experience. Phacoemulsification through a corneoscleral or clear-corneal wound with continuous curvilinear capsulorhexis probably is the method most likely to preserve capsular integrity. However, this method can be difficult in cases where vitreous hemorrhage obscures the red reflex. Experienced surgeons can perform pars plana phacoemulsification with retention of the anterior capsule and placement of an intraocular lens in the sulcus, or placement of an anterior chamber lens. No studies have been published showing a difference in outcome between these two methods. In many cases, vitrectomy can be performed with cataract extraction performed electively at a later time, although this requires that the patient undergo two surgeries. Regardless of the technique used, the risk of anterior segment neovascularization, pupillary membrane formation, and posterior synechiae still is present, and thus caution should be used when considering lens removal in patients with severe PDR.

SILICONE OIL IN DIABETIC VITRECTOMY

Another controversial topic is the role of silicone oil in patients with diabetic retinopathy. Whereas some authors^58,59 advocate using silicone oil in patients with severe PDR to promote stabilization or regression of iris neovascularization, others⁶⁰ question its benefit in diabetic patients. Lean and associates were the first to use silicone oil with vitrectomy for severe PDR.⁶¹ Several others have since published series of patients where silicone oil was used for severe PDR.^62–68 Many of these series involved eyes that had failed prior vitrectomy for PDR and had recurrent retinal detachment with proliferative vitreoretinopathy and iris neovascularization (Fig. 7). These eyes have a particularly poor prognosis and often lose all vision and progress to phthisis. For series that included only such eyes, anatomic success (total retinal reattachment) ranged from 30% to 70%, which may be higher than expected without silicone oil. Visual acuity results, however, remained disappointing. In addition, several complications of silicone oil were reported, including cataract formation, keratopathy, glaucoma, and redetachment secondary to reproliferation. Other reports have examined the use of silicone oil for recurrent vitreous hemorrhages after vitrectomy.^37,69,70 Gabel and Beck report a series of 135 consecutive cases of pars plana vitrectomy for PDR where balanced salt solution was used in 69 eyes and silicone oil was used in 66 eyes as a vitreous substitute.⁷¹ Indications for use of silicone oil included the presence of several retinotomies or retinectomies, or sharply increased risk for rebleeding. Postoperatively, for eyes with a minimum of 6 months' follow-up (only 58 of 135 eyes), the two groups achieved similar functional results, with 18 of 23 eyes (78%) in the silicone oil group and 27 of 35 eyes (77%) in the balanced salt solution group achieving visual acuity greater than or equal to 0.02 (4/200). A worse functional outcome would be expected from the eyes where silicone oil was used because of a worse preoperative condition. Thus, these findings may indicate that silicone oil is useful in such eyes. However, no comparison was made to similar eyes treated with long-acting gas tamponade. Certain characteristics of silicone oil may be advantageous for eyes with PDR. Because of its optical qualities, earlier visual rehabilitation may be possible, and fundus details are clearly visible, permitting intraoperative and postoperative laser photocoagulation. Also, silicone oil, unlike gases, provides indefinite retinal tamponade. Experimental evidence in animal models suggests that silicone oil may inhibit iris neovascularization by compartmentalizing the eye and preventing anterior diffusion of vasoproliferative substances.^57,72 However, clinical studies have been unable to confirm this because of the multiple variables that may lead to iris neovascularization. Oil emulsification and reproliferation may be more common in diabetics than in nondiabetic patients. If silicone oil is to be used in an aphakic or pseudophakic eye of a diabetic, it is important to create a large inferior iridectomy to prevent silicone oil from migrating anteriorly and contacting the cornea. Madreperla and McCuen showed that postoperative closure of the iridectomy occurs more frequently in diabetics than in nondiabetics, and closure of the iridectomy is highly correlated with anterior oil migration.⁷³

SURGICAL ADJUVANTS

Tissue Plasminogen Activator

Tissue plasminogen activator is a potent fibrinolytic agent that has been shown to be effective in dissolving fibrin membranes, which may complicate vitrectomy and other ocular surgeries.^74,75 It is advisable to wait approximately 1 week postoperatively before giving tPA for this purpose because, if given too soon, rebleeding may occur, and the fibrin membranes may reform. tPA should be used only in cases of severe fibrin deposition, where it is unlikely that the fibrin membranes will not resolve spontaneously. The use of tPA should be avoided if retinectomy has been performed because of the risk of bleeding from the cut edge of the retina. Caution also should be used with regard to the use of tPA in eyes with active rubeosis because of the risk of hyphema.

Other possible uses for tPA in diabetic patients remain controversial or unproven. Johnson and colleagues studied the effect of intravitreal tPA injection on clearance of experimentally induced vitreous hemorrhage in nonvitrectomized and gas vitrectomized rabbit eyes.⁷⁶ A statistically significant reduction in vitreous hemorrhage was found for both groups receiving tPA; however, this was thought to represent only a modest clinical effect. Use of tPA for this purpose has not been extensively studied in humans and has not gained widespread acceptance. Also, tPA has been evaluated as a possible agent for pharmacologic inducement of posterior vitreous detachment.⁷⁷ Inducing a posterior vitreous detachment could prove to be beneficial in diabetic patients because the posterior vitreous surface provides a scaffold for proliferation of retinal neovascular vessels in PDR.

Plasmin

Plasmin, a serine protease, also has been evaluated for possible use in inducing posterior vitreous detachment.⁷⁷ As with tPA, the safety and effectiveness of plasmin in producing this effect has not been shown convincingly for widespread acceptance.

5-Fluorouracil

Fluorouracil (5-FU), a synthetic pyrimidine analog, has been shown to reduce the rate of tractional retinal detachment and intraocular neovascularization in a rabbit model of massive periretinal proliferation.^78,79 Blankenship evaluated intravitreal injection of 5-FU as an adjunct to pars plana vitrectomy.⁸⁰ Fifty-one patients were randomized to receive a single 10-mg injection of 5-FU at the end of surgery versus no injection. Forty of these patients were undergoing vitrectomy for complications of diabetic retinopathy. Although no permanent toxic damage was seen because of 5-FU, no statistically significant difference was found between the two groups for rate of macular reattachment or in visual acuity. 5-FU has not gained acceptance as a surgical adjuvant in diabetic vitrectomy because no randomized study has conclusively shown a beneficial effect in humans and because of persistent concerns about ocular toxicity.

Heparin

Several investigators have evaluated the possible use of low molecular weight heparin sodium for use as an adjuvant in vitrectomy. Iverson and colleagues demonstrated in a rabbit model that infusion of 5 IU/ml of low molecular weight heparin sodium during lensectomy, vitrectomy, and retinotomy eliminated or reduced fibrin exudation.⁸¹ No significant difference in the degree of vitreous hemorrhage was noted between heparin-treated eyes and controls. Johnson and coworkers also demonstrated in a rabbit model that heparin, when given as a single anterior chamber injection, in the infusion solution, or as a single intravenous injection, resulted in a statistically significant reduction of postoperative fibrin.⁸² In human studies, heparin also was found to reduce postoperative fibrin formation; however, a significant increase in intraoperative bleeding was noted.^83,84 Additionally, no statistically significant difference was found between heparin and control in the rate of reproliferation after vitrectomy for PDR. Because of the potential for increased intraoperative hemorrhage and because no benefit has been shown in terms of reproliferation, the use of heparin in diabetic vitrectomy where vascular membranes are often cut is uncertain.

Thrombin

Thrombin is a blood protein that facilitates hemostasis by converting fibrinogen to fibrin within the clotting cascade. The use of thrombin to control intraocular hemorrhage during vitrectomy has been studied.^85,86 Addition of bovine thrombin (100 U/ml) to the vitrectomy infusate was associated with less overall bleeding during vitrectomy and less vitreous hemorrhage on the second postoperative day in a double-blind randomized study.⁸⁵ The use of thrombin was, however, associated with increased postoperative intraocular inflammation in 20% of patients. Another concern regarding the use of thrombin during vitrectomy is the possibility of promoting a severe postoperative fibrin reaction with consequent membrane proliferation. Washing out the vitreous cavity with infusate free of thrombin may decrease the risk of this occurrence.

1. Klein R, Klein BEK: Vision disorders in diabetes. In National Diabetes Data Group: Diabetes in America: Diabetes Data Compiled 1984, (DHHS publ. no. [NIH] 85–1468). Bethesda, MD, U.S. Department of Health and Human Services, 1985

2. Diabetic Retinopathy Study Research Group: Preliminary report on effects of photocoagulation therapy. Am J Ophthalmol 81:383, 1976

3. Diabetic Retinopathy Study Research Group: Photocoagulation treatment of PDR: Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS report no. 8. Ophthalmology 88:583, 1981

4. Early Treatment Diabetic Retinopathy Study Research Group: Photocoagulation for diabetic macular edema, ETDRS report no. 1. Arch Ophthalmol 103:1796, 1985

5. Early Treatment Diabetic Retinopathy Study Research Group: Pars plana vitrectomy in the early treatment diabetic retinopathy study, ETDRS report no. 17. Ophthalmology 99:1351, 1992

6. Machemer R, Buettner H, Norton EWD, Parel JM: Vitrectomy: A pars plana approach. Trans Am Acad Ophthalmol Otolaryngol 72:410, 1968

7. Machemer R, Parel JM, Buettner H: A new concept for vitreous surgery. I. Instrumentation. Am J Ophthalmol 74: 1, 1972

8. Machemer R: Vitrectomy in diabetic retinopathy removal of preretinal proliferations. Trans Am Acad Ophthalmol Otolaryngol 79:OP-394, 1975

9. Fox GM, Blumenkranz MS, Iverson DA et al: Long-Acting Gas Intraocular Tamponade in Diabetic Vitrectomy. American Academy of Ophthalmology Annual Meeting, Dallas, November 1992

10. The Silicone Study Group: Vitrectomy with silicone oil or sulfur hexafluoride gas in eyes with severe proliferative vitreoretinopathy: Results of a randomized clinical trial. Arch Ophthalmol 110:770, 1992

11. The Silicone Study Group: Vitrectomy with silicone oil or perfluoropropane gas in eyes with severe proliferative vitreoretinopathy: Results of a randomized clinical trial. Arch Ophthalmol 110:780, 1992

12. Mathis A, Pagot V, David JL: The use of perfluorodecalin in diabetic vitrectomy. Fortschr Ophthlmol 88:148, 1991

13. Williams DF, Williams GA, Hartz A et al: Results of vitrectomy for diabetic traction retinal detachments using the en bloc excision technique. Ophthalmology 99:1351, 1992

14. Pendergast SD, Martin DF, Proia AD, Jaffe GJ et al: Removal of optic disc stalks during diabetic vitrectomy. Retina 15:25, 1995

15. Diabetic Retinopathy Vitrectomy Study Group: Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Arch Ophthalmol 108:958, 1990

16. Diabetic Retinopathy Vitrectomy Study Group: Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Arch Ophthalmol 108:958, 1990

17. Thompson JT, DeBustros S, Michels RG, Rice TA: Results and prognostic factors in vitrectomy for diabetic vitreous hemorrhage. Arch Ophthalmol 105:191, 1987

18. Charles S, Flinn CE: The natural history of diabetic extramacular traction retinal detachment. Arch Ophthalmol 99:66, 1981

19. Blankenship GW: Preoperative prognostic factors in diabetic pars plana vitrectomy. Ophthalmology 89:1246, 1982

20. Thompson JT, DeBustros S, Michels RG, Rice TA: Results and prognostic factors in vitrectomy for diabetic traction retinal detachment of the macula. Arch Ophthalmol 105: 497, 1987

21. Thompson JT, DeBustros S, Michels RG, Rice TA: Results and prognostic factors in vitrectomy for diabetic traction-rhegmatogenous retinal detachment. Arch Ophthalmol 105: 503, 1987

22. Davis MD: Vitreous contraction in PDR. Arch Ophthalmol 74:741, 1965

23. Diabetic Retinopathy Vitrectomy Research Group: Two year course of visual acuity in severe PDR with conventional management. Ophthalmology 92:492, 1985

24. Lewis H, Abrams GW, Blumenkranz MS, Campo RV: Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 99:753, 1992

25. Harbour JW, Smiddy WE, Flynn HW, Rubsamen PE: Vitrectomy for diabetic macular edema associated with a thickened and taut posterior hyaloid membrane. Am J Ophthalmol 121:405, 1996

26. Tachi N, Ogino N: Vitrectomy for diffuse macular edema in cases of diabetic retinopathy. Am J Ophthalmol 122: 258, 1996

27. Keates RH, McGowan KA: The effect of topical indomethacin ophthalmic solution in maintaining mydriasis during cataract surgery. Ann Ophthalmol 16:1116, 1984

28. Allaire C, Lablache CM, Trinquand C, Bazin R: Comparative efficacy of 0. 1% indomethacin eye drops, 0.03% flurbiprofen eye drops and placebo for maintaining peroperative mydriasis. J Fr Ophthalmol 17:103, 1994

29. Haimann MH, Abrams GW: Prevention of lens opacification during diabetic vitrectomy. Ophthalmology 91:116, 1984

30. Oyakawa RT, Schachat AP, Michels RG, Rice TA: Complications of vitreous surgery for diabetic retinopathy. I. Intraoperative complications. Ophthalmology 90:517, 1983

31. DeBustros S, Glaser BM, Johnson MA: Thrombin infusion for the control of intraocular bleeding during vitreous surgery. Arch Ophthalmol 103:837, 1985

32. Oyakawa RT, Schachat AP, Michels RG, Rice TA: Complications of vitreous surgery for diabetic retinopathy. Ophthalmology 90:517, 1983

33. Kreiger AE: Wound complications in pars plana vitrectomy. Retina 13:335, 1993

34. Cleary PE, Ryan SJ: Method of production and natural history of experimental posterior penetrating eye injury in the rhesus monkey. Am J Ophthalmol 88:212, 1979

35. Campochiaro PA, Jerlan JA, Glaser BM: Serum contains chemoattractants for human pigment epithelial cells. Arch Ophthalmol 102:1830, 1984

36. Tardif YM, Schepens CL: Closed vitreous surgery. XV. Fibrovascular ingrowth from the pars plana sclerotomy. Arch Ophthalmol 95:235, 1977

37. Blumenkranz MS: Lens-sparing treatment of recurrent diabetic vitreous hemorrhage associated with anterior neovascularization by silicone oil injection, cryopexy, and laser photocoagulation. In Stirpe M (ed): Anterior and Posterior Segment Surgery: Mutual Problems and Common Interests. Acta of the Fifth International Congress on Vitreoretinal Surgery, pp 60, 176. New York, Ophthalmic Communication Society, 1998

38. Michels RG: Vitreoretinal and anterior segment surgery through the pars plana. Part I. Ann Ophthalmol 8:1353, 1976

39. Michels RG, Stark WJ: Vitrectomy technique in anterior segment surgery. Trans Am Acad Ophthalmol Otolaryngol 81:382, 1976

40. The Silicone Study Group: Vitrectomy with silicone oil or perfluoropropane gas in eyes with severe proliferative vitreoretinopathy: Results of a randomized clinical trial. Arch Ophthalmol 110:780, 1992

41. Williams GA, Lambrou FH, Jaffe GA et al: Treatment of post-vitrectomy fibrin formation with intraocular tissue plasminogen activator. Am J Ophthalmol 106:1055, 1988

42. Brownlee M, Vlassara H, Cerami A: Inhibition of heparin-catalyzed human antithrombin III activity by non-enzymatic glycosylation: Possible role in fibrin deposition in diabetes. Diabetes 33:532, 1984

43. Sowers JR, Tuck ML, Sowers DK: Plasma antithrombin III and thrombin generation time: Correlation with hemoglobin A₁ and fasting serum glucose in young diabetic women. Diabetes Care 3:665, 1980

44. Aaberg TM, Flynn HW Jr, Schiffman J, Newton J: Nosocomial acute-onset postoperative endophthalmitis survey: A 10-year review of incidence and outcomes. Ophthalmology 105:1004, 1998

45. Cohen SM, Flynn HW Jr, Murray TG et al: Endophthalmitis after pars plana vitrectomy. Ophthalmology 102:705, 1995

46. Meredith TA: Antimicrobial pharmacokinetics in endophthalmitis treatment: Studies of ceftazidime. Trans Am Ophthalmol Soc 91:653, 1993

47. Endophthalmitis Vitrectomy Study Group: Results of the endophthalmitis vitrectomy study: A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol 113:1479, 1995

48. Rice TA, Michels RG, Maguire MG, Rice EF: The effect of lensectomy on the incidence of iris neovascularization and neovascular glaucoma after vitrectomy for diabetic retinopathy. Am J Ophthalmol 95:1, 1983

49. Kokame GT, Flynn HW, Blankenship GW: Posterior chamber intraocular lens implantation during diabetic pars plana vitrectomy. Ophthalmology 96:603, 1989

50. Blankenship GW: Posterior chamber intraocular lens implantation during pars plana lensectomy and vitrectomy for diabetic complications. Graefes Arch Clin Exp Ophthalmol 227:136, 1989

51. Blankenship GW, Flynn HW, Kokame GT: Posterior chamber intraocular lens insertion during pars plana lensectomy and vitrectomy for complications of PDR. Am J Ophthalmol 108:1, 1989

52. Benson WE, Brown GC, Tasman W, McNamara JA: Extracapsular cataract extraction, posterior chamber lens insertion, and pars plana vitrectomy in one operation. Ophthalmology 97:918, 1990

53. Slusher MM, Seaton AD: Loss of visibility caused by moisture condensation on the posterior surface of a silicone intraocular lens during fluid/gas exchange after posterior vitrectomy. Am J Ophthalmol 118:667, 1994

54. Eaton AM, Jaffe GJ, McCuen BW II, Mincey GJ: Condensation on the posterior surface of silicone intraocular lenses during fluid-air exchange. Ophthalmology 102:733, 1995

55. Hainsworth DP, Chen SN, Cox TA, Jaffe GJ: Condensation on polymethylmethacrylate, acrylic polymer, and silicone intraocular lenses after fluid-air exchange in rabbits. Ophthalmology 103:1410, 1996

56. Kusaka S, Kodama T, Ohashi Y: Condensation of silicone oil on the posterior surface of a silicone intraocular lens during vitrectomy. Am J Ophthalmol 121:574, 1996

57. Khawly JA, Lambert RJ, Jaffe GJ: Intraocular lens changes after short- and long-term exposure to intraocular silicone oil: An in vivo study. Ophthalmology 105:1227, 1998

58. Lucke KH, Foerster MH, Laqua H: Lon-term results of vitrectomy and silicone oil in 500 cases of complicated retinal detachments. Am J Ophthalmol 104:624, 1987

59. DeJuan E Jr, Hardy M, Hatchell DL, Hatchell MC: The effect of intraocular silicone oil on anterior chamber oxygen pressure in cats. Arch Ophthalmol 104:1063, 1984

60. Yeo JH, Glaser BM, Michels RG: Silicone oil in the treatment of complicated retinal detachments. Ophthalmology 94:1109, 1987

61. Lean JS, Leaver PK, Cooling RJ, McLeod D: Management of complex retinal detachments by vitrectomy and fluid/silicone exchange. Trans Ophthalmol Soc UK 102:203, 1982

62. Mcleod D: Silicone-oil injection during closed microsurgery for diabetic retinal detachment. Graefes Arch Clin Exp Ophthalmol 224:55, 1986

63. Rinkoff JS, De Juan E Jr, McCuen BW II: Silicone oil for retinal detachment with advanced proliferative vitreoretinopathy following failed vitrectomy for PDR. Am J Ophthalmol 101:181, 1986

64. DeCorral LR, Peyman GA: Pars plana vitrectomy and intravitreal silicone oil injection in eyes with rubeosis iridis. Can J Ophthalmol 21:10, 1986

65. McCuen BW II, Rinkoff JS: Silicone oil for progressive anterior ocular neovascularization after failed diabetic vitrectomy. Arch Ophthalmol 107:677, 1989

66. Heimann K, Dahl B, Dimopoulos S, Lemmen KD: Graefes Arch Clin Exp Ophthalmol 227:152, 1989

67. Gonvers M: Temporary silicone oil tamponade in the treatment of complicated diabetic retinal detachments. Graefes Arch Clin Exp Ophthalmol 228:415, 1990

68. Bourman ND, Blumenkranz MS, Cox MS, Trese MT: Silicone oil for the treatment of severe PDR. Ophthalmology 96:759, 1989

69. Gnad H, Skorpik C, Paroussis P et al: Temporary silicone oil implantation following vitrectomy in PDR. Klin Monatsbl Augenheilkd 189:388, 1986

70. Hoerauf H, Roider J, Bopp S et al: Endotamponade with silicon oil in severe proliferative retinopathy with attached retina. Ophthalmologe 92:657, 1995

71. Gabel VP, Beck P: Does silicone oil improve the prognosis of severe proliferative diabetic retinopathy? Klin Monatsbl Augenheilkd 197:112, 1990

72. Glaser BM, D'Amore PA, Michels RG et al: Demonstration of vasoproliferative activity from mammalian retina. J Cell Biol 84:298, 1980

73. Madreperla SA, McCuen BW II: Inferior peripheral iridectomy in patients receiving silicone oil: Rates of postoperative closure and effect on oil position. Retina 15:87, 1995

74. Jaffe GJ, Lewis H, Han DP et al: Treatment of postvitrectomy fibrin pupillary block with tissue plasminogen activator. Am J Ophthalmol 108:170, 1989

75. Jaffe GJ, Abrams GW, Williams GA, Han DP: Tissue plasminogen activator for postvitrectomy fibrin formation. Ophthalmology 97:184, 1990

76. Johnson RN, Olsen KR, Hernandez E: Intravitreal tissue plasminogen activator treatment of experimental vitreous hemorrhage. Arch Ophthalmol 107:891, 1989

77. Verstraeten TC, Chapman C, Hartzer M et al: Pharmacologic induction of posterior vitreous detachment in the rabbit. Arch Ophthalmol 111:849, 1993

78. Blumenkranz MS, Ophir A, Claflin AJ, Hajek A: Fluorouracil for the treatment of massive periretinal proliferation. Am J Ophthalmol 94:458, 1982

79. Borhani H, Peyman GA, Thompson R, Thompson H: Suppression of experimental proliferative vitreoretinopathy by sustained intraocular delivery of 5-FU. Int Ophthalmol 19:43, 1995

80. Blankenship GW: Evaluation of a single intravitreal injection of 5-fluorouracil in vitrectomy cases. Graefes Arch Clin Exp Ophthalmol 227:565, 1989

81. Iverson DA, Katsura H, Hartzer MK, Blumenkranz MS: Inhibition of intraocular fibrin formation following infusion of low-molecular-weight heparin during vitrectomy. Arch Ophthalmol 109:405, 1991

82. Johnson RN, Balyeat E, Stern WH: Heparin prophylaxis for intraocular fibrin. Ophthalmology 94:597, 1987

83. Johnson RN, Blankenship G: A prospective randomized clinical trial of heparin therapy for postoperative intraocular fibrin. Ophthalmology 95:312, 1988

84. Williams RG, Chang S, Comaratta MR, Simoni G: Does the presence of heparin and dexamethasone in the vitrectomy infusate reduce reproliferation in proliferative vitreoretinopathy? Graefes Arch Clin Exp Ophthalmol 234:496, 1996

85. Thompson JT, Glaser BM, Michels RG, DeBustros S: The use of intravitreal thrombin to control hemorrhage during vitrectomy. Ophthalmology 93:279, 1986

86. DeBustros S, Glaser BM, Johnson MA: Thrombin infusion for the control of intraocular bleeding during vitreous surgery. Arch Ophthalmol 103:837, 1985