Update on Surgery For Macular Hole and Pucker

New advances and continuing controversies.

ALEX YUAN, MD, PhD

Continued advances in surgical techniques and instrumentation have made surgery for macular pucker and macular hole one of the most successful and gratifying procedures for vitreoretinal surgeons.

The earliest descriptions of membranectomy for epiretinal membrane were fraught with complications with only modest success rates. For example, Machemer described six patients undergoing vitrectomy with membranectomy and a long-term success rate of only 50% for visual gain.¹ The success rates quickly improved, with visual improvement seen in 90% of patients just three years later.²

Similarly, for macular hole surgery, the earliest reports by Kelly and Wendel described a 42% rate of hole closure in 52 eyes.³ Just two years later, this same group reported an updated study including 170 eyes with a success rate of 73%.⁴ Today, success rates for both types of surgery are greater than 90%. In this review, we will discuss the current controversies and advances in the surgical management of these macular pathologies.

ADVANCES AND CONTROVERSIES

Today, the vast majority of vitreoretinal surgeons in the United States have adopted small-gauge (23- and 25-gauge) vitrectomy for the treatment of both macular pucker and macular holes. Most surgeons will elevate the hyaloid and perform a complete vitrectomy before performing a membranectomy.

For macular pucker, some surgeons advocate double peeling, with removal of the internal limiting membrane after removal of the ERM. For macular hole surgery, some surgeons will similarly peel the ILM.

Figure 1. A partially peeled ILM using intraoperative OCT. Image obtained during surgery using a microscope mounted prototype (Bioptigen). Note the partially peeled ILM (arrow). To the left of the arrow, where the ILM is intact, the surface of the retina is smooth. To the right, where the ILM has been peeled, the surface has a feathered appearance. Note also the increased hyporeflectivity between the retina and RPE (arrowhead) following membranectomy.

COURTESY: JUSTIS P. EHLERS, MD

Intraoperative Dyes, Stains

As more and more surgeons peel the ILM, they are developing methods to help visualize the ILM during surgery. For example, new formulations of membrane dyes, such as Brilliant blue, in addition to indocyanine green, have been developed with good results.

Also, mixtures of dyes with high-density dextrose or polyethylene glycol solution have improved the staining of the macula. With all of these dyes and formulations, concern always exists regarding chemical or phototoxicity. So new methods to improve the visualization of the ILM are in development.

One example is the use of intraoperative optical coherence tomography (iOCT). If real-time iOCT becomes a reality, this technique may offer new ways of visualizing the ILM during vitrectomy with immediate surgical feedback.

Gas Tamponade and Positioning

For macular hole repair, surgeons have used nonexpansile intraocular gas tamponade since the earliest reports. They initially used shorter-acting sulfur hexafluoride (SF₆) gas, but they have also described longer-acting agents, such as perfluoropropane (C₃F_g).

Many surgeons recommend face-down positioning for one week or longer after surgery to maximize success rates of hole closure. However, surgeons have recently called into question both the need for long-acting gas and the necessity of postoperative positioning.

Furthermore, early postoperative OCT has emerged, which may perhaps help management decisions with regard to patient positioning.

Surgical Options

More surgeons are turning to combined vitrectomy and cataract surgery for both macular pucker and macular hole surgery. The rate of cataract formation after vitrectomy is very high, with more than 80% of patients reported to have a visually significant cataract two years after vitrectomy.

With the adoption of the Patient Protection Affordable Care Act, with its demands of greater efficiency and lower cost, combined surgery is beginning to make more sense in the United States, and it is already common abroad.

Finally, some surgeons have described membranectomy in nonvitrectomized eyes for macular pucker. This method prevents cataract progression because the surgeon does not perform vitrectomy. However, its safety and effectiveness remain to be seen, and patient selection is likely to be critical for success.

Figure 2. Example of a high-quality scan through gas. A) Preoperative scan shows a full-thickness hole with a pseudo-operculum (arrow). B) Postoperative day 1 scan through gas shows a closed hole with a vertical hyper-reflective line (arrowhead), presumably at the site of tissue apposition.³³

COURTESY: WOLTERS KLUWER

TO PEEL OR NOT TO PEEL

Macular pucker surgery changed very little in the 20 years since Machemer described this procedure. In general, the surgeon removed the ERM after performing a complete vitrectomy without addressing the ILM. Outcomes were good with improvement in vision in up to 90% and a low recurrence rate of 5% to 7%.^5-7

With the advent of staining techniques and OCT, it became increasingly popular to stain and peel the ILM in addition to peeling the ERM (double peel). Staining techniques allowed for the surgeon to visualize the ILM intraoperatively, and high-resolution spectral-domain OCT added improved postoperative assessment of macular anatomy with an anatomic measure of surgical success.

Some surgeons believe that cellular remnants of the ERM can proliferate on an ILM scaffold, causing recurrence of macular pucker.⁸ Thus, complete removal of the ILM should reduce the recurrence rate.

Evidence From the Literature

Indeed, several studies have shown that double peeling reduces the recurrence rate for macular pucker. A large prospective study from Japan showed no difference in visual acuity between single-peel and double-peel groups, but it noted a higher reoperation rate in the single-peel group (5.8% vs 0%).⁹

Another large retrospective study found that ILM peeling was the only factor associated with preventing recurrence (OR=0.33, P=.026).¹⁰ Although the long-term visual outcomes are similar for double peeling vs single peeling, some studies have suggested that visual recovery is slower with double peeling, and retinal edema is more prevalent after ILM peeling.^11,12

The evidence favoring ILM peeling for macular hole repair is even more compelling, with most studies reporting higher rates of hole closure after ILM peeling. A large, prospective trial showed the rate of hole closure at one month was 84% in the ILM peel group compared with 48% in the no-peel group (OR=6.23, P<.001), with fewer reoperations performed at six months (12% vs 48%, OR=0.14, P<.001).¹³

A recent meta-analysis evaluating four randomized, controlled trials also concluded the rate of hole closure was significantly higher in the ILM peel group (OR=9.27, 95% CI 4.98 to 17.24).¹⁴ The evidence supports a clear role for ILM peeling in macular hole surgery.

Figure 3. Example of a moderate quality scan, where a persistent hole can be easily missed. The open hole (A) is difficult to see clearly in this moderate quality image. One week later (B), the scan quality improves, and a persistent macular hole is obvious (asterisk).³³

COURTESY: WOLTERS KLUWER

SURGICAL DYES

Today, the primary choices for surgical dyes and stains include triamcinolone, ICG, and Brilliant blue. Toxicity studies have suggested that of these choices, ICG may be the most toxic to neurons and the RPE.^15-17 This toxicity may partially be related to phototoxicity or the light-induced degradation of ICG into toxic products.¹⁸

Some clinical data also suggest that ICG used intraoperatively can cause changes to the RPE.^19,20 However, most studies have suggested that ICG, diluted to 0.05%, while limiting light exposure and operative time, is safe.^21,22

While triamcinolone and Brilliant blue were found to be safer in toxicity studies, their use is limited because triamcinolone stains the ILM poorly, and Brilliant blue is not readily available in the United States.

INTRAOPERATIVE OCT

Several groups are exploring the use of intraoperative OCT or iOCT for vitreoretinal surgery. Possible applications for iOCT include identification of the ILM intraoperatively without the use of dyes (Figure 1) and confirmation of complete removal of the ILM after membranectomy.^23-25,44 Current prototypes of iOCT do not provide immediate surgeon feedback (ie, the surgeon cannot use iOCT to complete the membranectomy), but future models might integrate the device into the surgical microscope and allow for immediate and real-time visualization of the retinal anatomy.

AIR OR GAS?

Although debate exists on this topic, most surgeons will agree a short-acting tamponade, such as SF₆ is sufficient for primary repair of most macular holes. However, some surgeons have advocated for even shorter-acting agents, such as sterile air, with reports of similar hole closure rates.^26,27

In general, air tamponade reduced the time patients in these studies spent in the prone position. The effectiveness of air as a tamponade agent for macular holes is still under investigation. A lack of evidence exists supporting equivalence from randomized, controlled trials. Also, evidence has been lacking from large, retrospective trials using systematic approaches by reviewing all hole sizes and standardized surgical techniques.

The main advantage to air tamponade is faster visual recovery, but the difference in absorption rate between air and SF₆ is less than two weeks. So the surgeon must weigh the benefits of air tamponade against the potential risks.

WHAT’S YOUR FAVORITE POSITION?

One of the most difficult aspects of macular hole surgery is the face-down positioning that patients must endure in the postoperative period. Many surgeons recommend a full week of positioning, while others tolerate a shorter duration.

Several reports have even demonstrated that prone positioning is not necessary at all after macular hole surgery. Three randomized, controlled trials reported equivalent rates of hole closure with prone vs no positioning for small macular holes <400 µm.^28-30 Prone positioning, however, was more effective for macular holes >400 µm.^28,29

As these studies suggested, case selection is important, and prone positioning is recommended in difficult cases or in cases with large macular holes. In these more challenging situations, early postoperative OCT imaging through the gas bubble may help select patients in whom prolonged face-down positioning is not necessary, and the hole will close early.^31,32

Challenges to Perioperative Imaging

It is important to note however, that OCT imaging on postoperative day 1 poses many challenges. In our study of OCT imaging through gas on postoperative day 1, only 11% of scans approached the quality of scans through a fluid-filled eye, and only 36% of scans produced detailed images through all retinal layers (ie, the inner segment-outer segment line can be clearly seen). Factors improving scan quality included pseudophakia, operative times, and macular surgery.³³

Others have reported much higher success rates, but these reports excluded phakic patients (except Sano et al). They also did not have a defined system for grading scan quality.³¹’³²’^34-36

High-quality scans are necessary to assess the status of the hole accurately on postoperative day 1 (Figure 2, page 57). For example, this scan of moderate quality did not show a macular hole on postoperative day 1 (Figure 3a, page 58). However, one week later, when the scan quality improved, a macular hole was clearly visible (Figure 3b).

Foveal localization is also very important. The scan protocol should maximize the probability of imaging through the fovea. Otherwise, the surgeon could easily miss a persistent macular hole.³³

COMBINED VITRECTOMY AND CATARACT SURGERY

Combined cataract surgery with vitrectomy is fairly common outside the United States. Combined surgery offers significant cost savings to both the patient and the healthcare system. The patient spends less time off work, and only needs to make one trip to the operating room instead of two. For the health-care system, the cost to provide one combined surgery is less than two separate surgeries.

These savings are reflected in the reduced facility fees and physician fees if a single surgeon performs both procedures. However, if a separate surgeon performs cataract surgery, then both surgeons are reimbursed the full amount for each surgery.

In addition to the economic arguments favoring combined surgery, vitrectomy also virtually guarantees the patient will develop visually significant cataracts, especially if she or he is elderly.^37,38

Although the complication rate for cataract surgery in vitrectomized eyes is generally no greater than normal eyes, anecdotal evidence exists of anterior-chamber instability, altered fluidics, and zonular laxity.

In further support of combined surgery, comparative studies have shown similar visual outcomes between combined and consecutive surgery but a faster recovery with combined surgery.^39,40 Complication rates were similar and perhaps favored the combined group.

Numerous case series have evaluated the safety and efficacy of combined surgery, but few studies have compared combined surgery with consecutive surgery in patients with macular pucker or macular hole.

We retrospectively reviewed the data from one vitreoretinal surgeon to minimize inconsistencies with surgical approach. Interestingly, our unpublished results of 310 patients undergoing macular surgery (161 combined and 149 consecutive) showed better visual outcomes in the combined group at one, three, six, and 12 months.

At 12 months the average VA was 20/40 in the combined group and 20/50 in the consecutive group (P=.0057). The macular hole primary closure rate was 92% in the combined group vs 81% in the consecutive group (P=.054). A significantly higher risk of recurrent macular hole occurred in the consecutive group (11% vs 3.1%, P=.008), as well as a higher risk of elevated IOP above 30 mm Hg in the consecutive group (27.5% vs 16.8%, P=.022).

These results suggest that combined surgery may be more effective and safer than consecutive surgeries. All of these factors together provide a compelling argument that favors combined surgery for macular puckers and macular holes.

MEMBRANECTOMY IN A NONVITRECTOMIZED EYE

Membranectomy without vitrectomy has appeared in the literature since 20-gauge vitrectomy was the norm. No infusion is necessary, and the risk of cataract formation is no greater than baseline.

With the initial report, the surgeon created a 20- or 23-g sclerotomy, through which a light pipe and microhook needle were inserted to perform the ERM peel.⁴¹ The surgeon either left the membrane floating in the vitreous or pulled it out through the sclerotomy site. The prolapsed vitreous was cut, and the surgeon closed the sclerotomy sites. Long-term follow-up showed no progression of cataract above the baseline rate. However, the ERM recurrence rate was higher than normal (33%).⁴²

With the advent of 27-gauge instruments, interest renews in nonvitrectomized membranectomies once again, but this time, without the need to close the sclerotomy site.⁴³

However, the risk of recurrent ERM is likely to be high because the surgeon cannot stain and peel the ILM. From the limited reports in the literature, there does not appear to be a higher risk of complications other than recurrent ERM. With the further development of iOCT, perhaps one day, surgeons will be able to perform an OCT-guided ILM peel in a nonvitrectomized eye.

CONCLUSIONS

Recent advances, such as small-gauge vitrectomy and membrane dyes, have made macular surgery more efficient with improved outcomes. Further development of surgical techniques and instrumentation, such as nonvitrectomized membrane peels and iOCT, may provide additional improvements to macular surgery in the future. RP

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