Surgery on Macular Holes

Why we still cannot close them all

Surgery on Macular Holes

Why we still cannot close them all.


Macular hole surgery, introduced by Kelly and Wendel in 1991 as one of the finest and most delicate ophthalmic surgeries,1 takes place weekly in the practice of any vitreoretinal surgeon. New surgical refinements, such as disposable end-gripping forceps or vital dyes, have been recently introduced to ensure a precise and optimal grip of the epiretinal membranes playing a role in this pathology and to improve their visualization for a safer and more complete removal. Even the diagnosis of eyes affected by macular holes has significantly improved with the advent of the high-resolution OCT, offering preoperative and postoperative images very close to histological samples.

Nevertheless, almost 20 years later, this surgery is still encumbered by a relatively high rate of failures, despite it being one of the most codified and discussed of all the vitreoretinal procedures. The rate of failures reported varies from 4% to 13%, not having changed too much in the last 10 years.2-5 The change to minimally invasive procedures, such as 23-, 25- and soon possibly 27-gauge vitrectomy, should have increased the successes due to a shorter and less traumatizing surgery. On the contrary, in our institution, after the passage from 20- to 23-g vitrectomy, we almost doubled our primary failure rate to 14.8%. Thus, we retrospectively analyzed some failed cases from the last two years to detect possible reasons.


We reviewed the charts of 54 patients operated on in our department between January 2008 and August 2009 for macular holes of stages 3 and 4. Surgeries were conducted by two experienced surgeons (the authors) under local anesthesia with a standard 23-g three-port vitrectomy. In all patients, the posterior hyaloid was removed by active suction in front of the optic disc after its visualization with triamcinolone acetonide.

In all cases, the internal limiting membrane was then peeled completely after staining with Brilliant Blue G using disposable end-gripping forceps. After a complete fluid-air exchange, the vitreous cavity was filled with a mixture of 20% SF6 or 15% C3F8 (for phakic and pseudophakic eyes, respectively) and the patients were asked to maintain face-down positioning at night and for at least eight hours in the daytime during the first five days postoperatively. Mean duration of the surgical procedure was 40 minutes and an uneventful phaco surgery was combined in only one case (64% of cases were phakic and 36% were pseudophakic at the time of surgery).

The diagnosis of a nonclosed macular hole was made biomicroscopically and confirmed with spectral-domain OCT within one month after vitrectomy, when the intraocular gas was completely reabsorbed.

Eight eyes of 54 patients failed at the first surgery. All of them were submitted to second surgeries, which were successful in all but one patient, who refused a third surgery. Two of the holes that failed to close (2/8) had a preoperative diameter of >800 μm; thus, we excluded them from the analysis that follows for their higher risk of failure.


Failures in macular hole surgery can be considered either holes that remained unclosed after the first intervention or holes that reopened in a variable period after a primary successful surgery.

Here we consider only the primary failures, because delayed re-openings of successfully closed macular holes could be related to such other factors as the growth of epiretinal membranes,6 a continued intraretinal and preretinal cellular remodeling, resultant traction7 or inflammatory reactions secondary to cataract surgeries that occur in phakic vitrectomized patients in 79.3% of cases within two years.8

The Relief of Tractions

Once the posterior pole has been completely released from the posterior hyaloid, the removal of the ILM has been widely accepted as another critical step for the short- and long-term results of macular hole surgery, although some surgeons still disagree in particular for small macular holes stage 2 or 3.9 Minimally invasive sutureless vitrectomies, with disposable, smaller, more precise instruments, make this maneuver easier and safer. Nevertheless, despite the many circumstances where the ILM is intraoperatively considered as peeled off together with the posterior hyaloid or with a concomitant epiretinal membrane, its fragments or large pieces are still detectable by staining the retinal surface. Thus, the use of vital dyes to visualize the membranes and achieve a more complete peeling has been adopted by the majority of surgeons.

Persistence of the ILM, in accordance also with most of literature, is one of the major reasons for the failures of this surgery (Figure 1a). Schumann et al. found remnants of ILM with newly formed collagen irregularly distributed on its surface as the predominant feature of specimens collected from the macular holes that failed to close at the first surgery.10 In a randomized study, Christensen et al. described how the removal of the ILM, both in stage 2 and stage 3 macular holes, was associated with a significantly higher closure rate compared to patients on whom any attempt was done to peel it.11 In the same study, there was a statistically significant association be tween other preoperative variables, such as the preoperative diameter of the hole or the duration of symptoms, and the final primary closure rate. This assertion was in contradiction to previous reports, in which ILM peeling did not seem to be necessary to achieve the 100% of primary closure rate for macular holes <400 µm in diameter.9

Figure 1. Schematic representation of four different reasons for failure: a. Persistence of large sheet of ILM (thin arrows). b. Residual inner ring of ILM (bold arrows). c. Inadequate tamponade. d. Pooling of vitreous remnants inside the hole (white asterisks) around the back-flush needle (thin white arrow).

The value of ILM removal even for these relatively small holes, as stressed by Didier Ducournau, MD, would be not only the release of the tangential tractions exerted on their rims but also the induction of a vertical gliosis stimulated by the peeling, which allows a better consolidation of the retina, reducing the risk of recurrences.12 It may even be speculated that this type of cellular injury in vivo stimulates regenerative mechanisms in the Müller cells that may contribute to the closure of the macular hole.13

The peeling of the ILM should be considered not only for relieving the rigidity of the retinal tissue surrounding the hole, but also because the ILM — as is true for any acellular surface — represents an optimal scaffold for the regrowth of epiretinal tangential membranes, which may induce early or late re opening of the hole.

Width of the ILM peeling is another matter that should be discussed. In other pathologies where macular edema is present, an extended peeling of the ILM is pursued by many surgeons due to the possibility of a striking effect exerted by the remaining unpeeled peripheral ILM on the edematous peeled macula. In eyes with macular hole, the rim of the unpeeled ILM surrounding the hole could become the scaffold for reproliferation of tangential tractions, somehow limiting the “mobility” of the foveal retina.14 This is in accordance with the evidence, from a bird's eye view, of a centrifugal cell's migrations, which increase on the ILM surface with the stage of the hole.15 In the literature, there are many different reports on the extent of the peeling of the ILM in macular hole surgery. Peeling is limited by some authors to one disc area centered on the fovea,16,17 or it is extended by others to two disc areas at least,18 to about three disc areas in other reports19-21 or even more in other cases.22

In one of our failures, the peeling in the first surgery had been extended and complete, and the staining with dyes at the second operation did not show any sign of ILM or epiretinal membrane remnants on a 4 mm area surrounding the open macular hole. The only appearance was a mild to intense staining of the inner borders of the hole with a stiff and regular consistency.

A ring-shaped remnant of ILM, resulting from a tearing of the ILM that occurs during the peeling maneuver, is another possible reason for failure (Figure 1b). This could be in part explained by the difference in the ILM thickness existing in the human eye. The ILM is a thin basement membrane in the pit of the fovea that gradually becomes a thick membrane in the parafovea and, in adults, shows an appositional deposition of Müller cell end-feet.23 Such a 4 µm-thick ILM adheres with strength to the collagenous cortex of the vitreous on its one side and to very small irregularly shaped Müller cell end-feet on the other retinal inner surface.24 Significant differences are clinically reported on the strength of adhesion between these layers by some authors who observed occasional complete preservation of the entire ILM covering the fovea at its removal during the surgery.25

Indeed, the traction exerted during the peeling maneuver could induce the ILM to tear off at the transitional site between areas of different thickness, leaving a rigid ring that could explain the reduced mobility of the hole to close. This latter ring could not allow the so-called kissing or bridging of neural retina over the optically empty subretinal space described by Masuyama in the scarring processes following the surgery.26

The Tamponade

Once the macular surface has regained sufficient mobility free of surface traction, either vertical or tangential, it is time to seal. In almost all macular holes, apart from very selected cases of small dimensions ≤200 µm that could close spontaneously without surgery in 2% of cases,27 at the end of the surgery it is necessary to tamponade the hole. Air, gas or silicone oil bubbles all serve to keep dry the edges of the hole and to provide a compartment and smooth surface for the glial cell proliferation that will seal it.28

Time and efficacy of face-down posturing is still an open debate. In 2009, Tatham and Banerjee conducted a meta-analysis of studies related to macular hole surgery and the successes obtained in relation to postoperative tamponade and face-down posturing.29 They considered only five studies that were suitable for meta-analysis relative to case control and concluded that there is currently insufficient evidence to draw firm conclusions as to whether face-down posturing influences macular hole closure rates. Studies on OCT in the early postoperative days have shown how holes can close 76.9% of the time after one day of face-down positioning,26 as reported also by Kasuga,30 or up to 93% of cases after two days.31 Conversely, Paul Tornambe, MD, had already in 1997 reported in a pilot study a similar success rate of 79% of closure without any positioning.32 Ten years later, Tranos et al. similarly did not see changes in the final anatomic and functional results, but an increase in cataract progression in 41 patients treated without positioning with a follow-up longer than four months.33 Guillaubey et al., in a comparative case of 150 eyes, found a significant correlation in the preoperative dimensions of the hole on the need for positioning, with face-down positioning unnecessary for holes smaller than 400 µm.34

The mechanisms of how the gases work are still not universally accepted:

  • Gases could work because of their buoyancy, which pushes the retina against the retinal pigment epithelium by a mechanical force based on the different gravities between them and the intraocular fluid.
  • Gases could work because of their surface tension in the aqueous media, which is greater than silicone oil and which helps them temporarily close the hole.

The “sealing” effect on the borders of the hole for a period of time sufficient for scar formation is the most important factor, as demonstrated by the evidence that, after filling the eye with gas, the hole can close without face-down positioning — indeed, without a significant buoyancy force, which only comes by directing the gas bubble upward to the hole. Furthermore, the 86% rate of successful anatomical results reported by Goldbaum et al. — without face-down positioning and with the use of silicone oil, which has even lower surface tension — seems to corroborate this theory.35

Thus, a watertight tamponade of the hole is mandatory, both with a three-quarter filling of the vitreous cavity and with severe posturing for the first 48 hours; the lack of a proper tamponade was the reason for another failure of ours.

Finally, after a complete peeling of the ILM with a careful mobilization of the borders, which could be confirmed by their gentle manipulation, as is practice of some surgeons, and a sufficient tamponade, it may still happen that the macular hole does not close. This is probably that small percentage of macular holes that lead to the question: “Why do we still have some unclosed holes despite almost every aspect of the development and treatment of this challenging clinical entity deepening?” In our thinking, the vitreous could be the answer.

As noted above, we observed in our practice a dramatic increase in primary failures after the passage from the traditional 20-g to smaller 23-g vitrectomy. Apart from the surgical refinements aforementioned, another significant difference between the two surgeries is the amount of vitrectomy. With the introduction of small-gauge techniques, the surgical time has been significantly reduced, to the detriment of the removal of vitreous gel. Although these systems have many advantages, they have lower flow rates than the traditional 20-g system. Because of this, vitreous removal has become a longer step, but the final amount of vitreous removed has become smaller, with a common tendency toward a core vitrectomy even for macular holes. Thus, more frequently, gel remnants will be observed pooled at the posterior pole at the end of the fluid-gas exchange (Figure 1d). The accumulation of these remnants inside the hole can be evidenced by the filamentous material that comes into the back-flush needle when completing the exchange maneuver on top of the hole during the first operation (Figure 2). Removal of such undesirable material in a gaseous environment is very hazardous, as reported by Margherio et al. in 2000.36 This pocket of gel left in place may become almost impossible to be removed and an obstacle to glial migration and closure of the hole, as reported by Schubert in an in vitro study.37

Figure 2. Intraoperative images of vitreous gel engaged in the back-flush needle at the end of the fluid-air exchange on top of the hole.


Reasons for failure in macular hole surgery are various. The preoperative diameter or the form of the hole, which can change with developments of the stage, as well as the status of the retinal pigment epithelium, can be responsible for an higher risk of primary failure.38 Other negative factors include the duration of symptoms, which somehow correlates with the status of RPE, or a cystic degeneration of the neurosensorial borders of the hole.

Surgical reasons for failures are the persistence of surface tractions and the inadequacy of the postoperative tamponade. The completeness of removal of all the membrane present on the retinal surface in a 4 mm diameter area around the hole and along its rim, as well as an adequate continual sealing of the same during the first 48 hours after surgery, are crucial for holes larger than 400 µm.

From the review of our latest failures (Table 1), we suggest that a pocket of residual vitreous gel pooled inside the hole is a possible additional reason. The switch to a minimally invasive surgery, which entails a possible reduced removal of vitreous gel due to a reduced flow rate compared to traditional 20-gauge vitrectomy, may be an explanation. The introduction of new systems with different duty cycles or an incomplete fluid-air exchange to avoid the intraoperative pooling of the gel inside the hole could be among the possible solutions.

Further investigation is needed to confirm and elaborate what, at the moment — due to the lack of histological or clear diagnostic and statistical evidence — remain only clinical impressions. RP

Vincenzo Ferrara, MD, is a vitreoretinal surgeon and chief of the Retina Division at the SS. Trinità Hospital of Arona, Italy. Vito Belloli, MD, is the chairman at the same hospital. Neither author reports any financial interests in any products mentioned in this article. Dr. Ferrara can be reached at


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