A Clinical Update on Vitrectomy for Diabetic Retinal Disease

Patient selection can significantly impact outcomes.

MICHELLE C. LIANG, MD • ANDRE J. WITKIN, MD

Diabetic retinopathy is a leading cause of blindness in the working population.^1,2 With increasing duration and poor control of diabetes mellitus, microvascular complications can cause progressive retinal damage and lead to retinal ischemia, macular edema, retinal neovascularization, vitreous hemorrhage, traction retinal detachment, and neovascular glaucoma.

Primary management of diabetic retinopathy includes intensive glycemic control, as well as the regulation of systemic blood pressure and lipid levels. Improved blood glucose control can decrease the risk of the development and progression of diabetic retinopathy.^3,4 However, even with good medical management, 5% of patients will ultimately develop complications that require surgical intervention.⁵

With advancing surgical instrumentation and technology, indications for the use of pars plana vitrectomy in diabetic retinopathy have expanded.

Common reasons for vitrectomy include nonclearing vitreous hemorrhage, traction retinal detachment, combined traction–rhegmatogenous retinal detachment, and, in some cases, diabetic macular edema (Table 1).

Table 1. Indications for Vitrectomy in Diabetic Retinopathy

INDICATIONS FOR VITRECTOMY IN DIABETES
Nonclearing vitreous hemorrhage	Traction retinal detachment involving the macula	Diabetic macular edema
Premacular hemorrhage	Combined traction-rhegmatogenous retinal detachment	Epiretinal membrane
Anterior-segment neovascularization with posterior-segment opacity	Anterior hyaloid proliferation	Ghost cell glaucoma

SMALL-GAUGE VITRECTOMY

Refined technologies in vitrectomy surgery have allowed for improved instrumentation and surgical efficiency compared to prior 20-gauge PPV systems. The introduction of minimally invasive 23- and 25-gauge systems to the market, which have now become standard in clinical practice, has permitted transconjunctival incisions and smaller sclerotomy size. Twenty-seven–gauge systems have also started to become available and may eventually become widely used in practice.

Fujii et al first described a 25-gauge PPV technique in 2002, which they termed microincisional vitrectomy surgery (MIVS).^6,7 It was described as minimally invasive, transconjunctival, sutureless surgery with the potential to increase efficacy in surgery and thus decrease operating time and minimize surgically induced trauma and postoperative inflammation.

Multiple benefits of 23- and 25-gauge vitrectomy systems have since been shown in comparison to 20-gauge vitrectomy, including faster wound healing, less conjunctival scarring, less induced corneal astigmatism, decreased operating time, more rapid visual recovery, and improved postoperative comfort.^8-11 In addition, less conjunctival scarring allows for repeated PPV or filtering surgery, if needed.

MIVS was initially advocated for only macular surgery due to the instrument limitations of the earlier small-gauge systems, but as new 23- and 25-gauge instruments have been developed, more recent reports have shown success in more complicated cases, including traction retinal detachment secondary to proliferative diabetic retinopathy.¹²

Other concerns with MIVS systems were related to wound-sealing complications, including postoperative hypotony, choroidal detachment, and a potential risk of increased endophthalmitis.

However, multiple reports have shown the incidence of these complications to be low, especially when care is taken to suture sclerotomies if they appear to be leaking at the end of surgery. Specifically, the rates of endophthalmitis between the systems appear to be no different.^10,13-15

Expanding Indications

The indications for diabetic vitrectomy are ever growing thanks to continued advancements in MIVS technology. Prior concerns about instrument flexibility, low aspiration and flow rates, and poor illumination have been overcome and are no longer true disadvantages to small-gauge surgery.

Valved cannulas have allowed for steadier intraocular pressures. Introduction of better noncontact widefield visualization systems, sturdier instrumentation, faster cutting speeds, improved illumination with endochandeliers and illuminating picks, and endolaser probes have allowed for more precise surgical maneuvers.

In particular, these technologies have permitted more efficient removal of dense fibrous tissue and preretinal membranes in diabetic eyes, which was not possible with the earlier 25-gauge systems.

While the main reasons for surgical intervention in diabetic retinopathy are largely unchanged, the indications and timing for PPV continue to evolve. The availability of MIVS in conjunction with improved instrumentation and visualization systems may lower the threshold for vitrectomy for some physicians, and earlier surgical intervention may be advisable.

PROLIFERATIVE DIABETIC RETINOPATHY

Panretinal photocoagulation is the first-line therapy for PDR. However, complications of PDR can arise before adequate PRP can be performed or even in the presence of seemingly adequate PRP. The goal of vitrectomy is to remove media opacity, relieve retinal traction (particularly macular traction), and perform PRP.¹⁶

Additionally, removing the vitreous, and in particular the posterior hyaloid, also stabilizes the influence of PDR on the retina by removing the scaffold for fibrovascular proliferation. In theory, it may also improve blood vessel perfusion and oxygen supply to the inner retina.^17,18

VITREOUS HEMORRHAGE

Vitreous hemorrhage is the most common complication of PDR. It can abruptly decrease vision and interfere with the application of adequate PRP treatment. It is thought to occur due to traction on the neovascular or fibrovascular complex from an incomplete posterior vitreous detachment.¹⁷

The initial management of vitreous hemorrhage is typically to wait some time for spontaneous clearance, with application of adequate PRP to decrease VEGF loads and halt and/or regress fibrovascular proliferation. Vitrectomy with endolaser has usually been reserved for persistent and nonclearing vitreous hemorrhage lasting for more than three months or for recurrent vitreous hemorrhage despite prior PRP.

Longer observation periods may be permitted for patients with type 2 diabetes, due to increased rates of spontaneous resolution and slower progression of fibrovascular proliferation, especially in the presence of prior PRP or complete PVD. However, earlier surgical intervention may be warranted if there has been no previous PRP treatment performed or in the presence of extensive fibrovascular proliferation, rapid progression of retinopathy, anterior-segment neovascularization, or pre-existing visual loss in the fellow eye.

Additionally, the Diabetic Retinopathy Vitrectomy Study showed a benefit to early intervention in patients with type 1 diabetes, as these patients tend to have more quickly progressing retinopathy, and delay of adequate PRP may lead to the development of fibrovascular proliferation and increased risk of retinal detachment.^19,20

Preretinal Hemorrhages

Subhyaloid or premacular hemorrhage is another indication for vitrectomy in patients with diabetic retinopathy (Figure 1A). Persistent hemorrhage can remain as a scaffold for further vitreoretinal adhesion, and constant retinal exposure to hemorrhage can lead to toxic damage, traction on the photoreceptors, and/or a physical barrier to the diffusion of nutrients and metabolites.

Figure 1. A) Significant premacular hemorrhage in a patient with proliferative diabetic retinopathy. B) Total traction retinal detachment in a patient with PDR.

Other factors to consider in surgical decision-making include visual acuity, degree of improvement in hemorrhage with observation, the preference and needs of the patient, his or her level of glycemic control, any medical comorbidities, and patient compliance with follow-up.

RETINAL DETACHMENT

The timing for vitrectomy in PDR-related retinal detachment is influenced by the etiology of the detachment and the proximity to the macula. Both traction and combination traction-rhegmatogenous retinal detachments can be complications of PDR. Traction retinal detachments occur due to traction of preretinal fibrovascular membranes on the retina (Figure 1B).

Peripheral localized traction detachments can often be observed due to slow progression, particularly if adequate PRP has been performed; however, they can progress to involve the macula in up to 14% of cases per year.²¹

Currently, intervention with vitrectomy is indicated for traction retinal detachments involving or threatening in the macula, as well as combined traction-rhegmatogenous retinal detachments. These are often complex surgeries due to thinning of the retina from ischemia and density and adherence of fibrovascular membranes to the retina.

Improvement in surgical techniques over the years has led to improved anatomic and functional success rates following surgery for complications of PDR.^22-24 Endoillumination with chandelier probes has allowed for a bimanual technique if needed, often with surgeons utilizing microforceps in one hand and another instrument in the other hand, such as a pick, vertical or horizontal scissors, vitrector, or viscoelastic to assist in tissue dissection.

The introduction of illuminating micropicks has also permitted bimanual surgery without the introduction of a chandelier light. Furthermore, adjunctive use of a long-lasting tamponade, such as silicone oil (Figure 2), can lead to an anatomic success rate of 80% to 87%, even in severe cases.

Figure 2. A) Preoperative color mosaic of a posterior traction retinal detachment related to PDR. B) Early postoperative color mosaic of an attached retina under silicone oil and fresh laser markings after vitrectomy, membrane peeling, endolaser, and silicone oil injection.

Despite these techniques, intra- and postoperative complications of traction retinal detachment repair are not uncommon, and they include intraoperative bleeding, iatrogenic breaks, recurrent or persistent vitreous hemorrhage, and hyphema with secondary glaucoma.²⁵

Adjunctive Anti-VEGF Therapy

Preoperative use of intravitreal bevacizumab (Avastin, Genentech, South San Francisco, CA) has been proposed to decrease both intraoperative bleeding and postoperative hemorrhage in patients undergoing vitrectomy for diabetic retinal detachment.

Chen and Park first reported the use of intravitreal bevacizumab as a preoperative adjunct for traction retinal detachment repair,²⁶ and multiple studies have since studied the effects of bevacizumab injection prior to surgery.^27-30

Oshima et al reported good success with both 23- and 25-gauge surgery in conjunction with preoperative bevacizumab, compared to their earlier surgeries with 20-gauge instruments. They also advised that timely surgery should be performed after bevacizumab injection in patients with traction detachments, as progression of detachment may occur after injection.²⁵

Pokroy et al²⁹ also advocated the use of preoperative bevacizumab, given an average of 11.5 days prior to vitrectomy in their study. The results included a shorter operating time in younger patients and a trend toward better vision with vitrectomy for traction detachment, although both surgical groups had improvements in vision.

Others have advocated the use of preoperative bevacizumab to reduce early postvitrectomy hemorrhage, with improved VA outcomes at six months and a decreased need for repeat vitrectomy.^31,32 However, other reports have shown no benefit at six months with pretreatment.³³

Small-gauge vitrectomy with or without pretreatment with intravitreal bevacizumab appears to be beneficial in patients with retinal detachment secondary to PDR. While there have been mixed reports on the benefits and optimal timing of pretreatment with bevacizumab, it may be a useful adjunct to vitrectomy surgery for diabetic retinal detachment. Further improvements in both medical and surgical technologies will hopefully lead to even greater improvement in patient outcomes.

DIABETIC MACULAR EDEMA

Although DME is a common cause of decreased vision in patients with diabetic retinopathy (Figure 3), the role of vitrectomy in DME has been more controversial compared to the other indications, because a multitude of medical therapies are the mainstay of treatment for this condition.

Figure 3. A) Color fundus photograph showing retinal hemorrhages and exudate in a patient with nonproliferative diabetic retinopathy. There is associated macular thickening. B) Cirrus (Carl Zeiss Meditec, Dublin, CA) spectral-domain OCT imaging displays diabetic macular edema with intraretinal fluid.

Historically, focal laser was the gold standard for treatment of DME, with a reduced risk of moderate vision loss in 50% of patients with clinically significant macular edema. However, with this treatment, 25% of patients still progressed to have moderate visual loss.³⁴

With the introduction of intravitreal corticosteroids and anti-VEGF agents, visual improvement has become the norm. Intravitreal corticosteroids lead to improvement in vision in many patients, but they can also accelerate cataract formation and cause increased IOP.³⁵

Because of these side effects, anti-VEGF agents have become the preferred first-line treatment option for most physicians in the treatment of DME.^36-39 However, despite these treatments, some patients still have significant vision loss.

As use of intravitreal anti-VEGF and corticosteroid medications continues to be studied, it is apparent that the etiology of DME is multifactorial, and vitrectomy may be a useful adjunct to help achieve improvement in or resolution of DME in some patients.

Diabetic macular edema has been demonstrated to be less prevalent in patients with a PVD than in those without a PVD. Additionally, separation of the vitreous has been noted to lead to resolution of macular edema in some patients.

Navarro et al were the first to suggest that vitrectomy may prevent the occurrence of DME.⁴⁰ Specifically, a taut hyaloid and/or inner limiting membrane was thought to cause tangential traction and exacerbate edema.^41-47

Vitreomacular Interface Abnormalities

Optical coherence tomography is an imaging technique that has led to the ability to detect abnormalities of the vitreomacular interface in great detail.^48,49 Preoperative OCT assessment of associated vitreomacular interface abnormalities in patients with DME can assist in clinical decision-making⁵⁰ as tractional effects on the macula can be better visualized.

Possible vitreomacular interface abnormalities that may contribute to DME include vitreomacular traction and epiretinal membrane,⁴⁹ as well as less well-defined findings such as a prominent posterior hyaloid and taut ILM (Table 2).

Table 2. Vitrectomy for DME

VITRECTOMY FOR DME
Taut posterior hyaloid membrane
Vitreomacular traction
Epiretinal membrane
Recalcitrant DME
Taut ILM

Patients with apparent signs of traction on examination or OCT may fare better with vitrectomy than those without^51,52; however, others have proposed vitrectomy with removal of the hyaloid or ILM, even without signs of excessive traction on OCT.

In these patients, it has been theorized that anatomic improvement may be achieved due to improved blood flow to the macula following vitrectomy and membrane peeling.⁵³

Surgical Results in DME

The role of vitrectomy in DME is still a matter of debate. According to the Diabetic Retinopathy Clinical Research Network, 68% of patients experienced at least a 50% reduction in macular thickening on OCT, but VA results were more variable, with some patients losing vision while others gained vision (Figures 4 and 5).⁵⁴ Additional studies have shown comparable results, with vitrectomy reducing macular thickness but not having as robust an effect on improving VA.^51,52,55,56

Figure 4. A) Preoperative Spectralis (Heidelberg Engineering, Carlsbad, CA) SD-OCT of persistent DME after four injections of intravitreal bevacizumab. Visual acuity was 20/200. The patient underwent pars plana vitrectomy with membrane peel and intraoperative injection of bevacizumab. B) One month after surgery, the vision improved to 20/70 with subsequent improvement in macular edema. There was mild residual subretinal fluid. C) At 14 months after surgery, the vision improved to 20/30 with restored foveal contour. The patient only required one injection of bevacizumab postoperatively.

Figure 5. A) Preoperative Spectralis SD-OCT of persistent DME after five injections of intravitreal bevacizumab (IVB) and one injection of intravitreal triamcinolone. Vision was 20/200. The patient underwent vitrectomy with membrane peel and intraoperative injection of triamcinolone. B) One week after surgery, there was improvement in macular edema and foveal contour but no improvement in vision. C) Twelve months after surgery, the vision remained at 20/200. The patient did not require postoperative intravitreal injections.

Vitrectomy, however, has typically been reserved for patients with long-standing macular edema refractory to other forms of medical treatment. The variable results after surgery may be confounded due to underlying damage from long-standing macular edema, as surgery is usually used as a last resort. It is possible that earlier intervention may yield better visual outcomes that correlate with the typical good anatomic outcomes.

CONCLUSION

An individualized treatment plan for patients with complications of diabetic retinopathy can involve a combination of laser, pharmacologic, and surgical treatments. A combination of approaches is often the best treatment option to maintain and improve vision in patients with diabetic retinopathy.

There is a high risk of visual loss from DME, retinal ischemia, vitreous hemorrhage, and/or traction retinal detachment. With newer and improved surgical techniques, earlier vitrectomy may be of greater benefit in certain patients with diabetic retinopathy.

The role of PPV in treatment of complications of diabetic retinopathy will continue to be investigated as advances in both medical and surgical treatment of these conditions continues to evolve. RP

REFERENCES