40 Surgical management of full-thickness macular hole

Background

Epidemiology

Idiopathic full-thickness macular hole (FTMH) occurs in approximately 1/3300 and predominantly affects patients in their sixth to eighth decades of life. A significant number (15–20%) of patients with a unilateral FTMH will develop fellow-eye involvement over the first five years.1

Aetiology and natural history

In 1988 and subsequently in 1995, Gass proposed that FTMH arise from tangential vitreofoveal traction as the posterior vitreous cortex contracts with progressive ageing.2,3 This results in centrifugal traction on the fovea, leading to a localised foveal detachment and loss of the foveal reflex and depression on biomicroscopy. This configuration is termed stage 1a or an impending hole and is associated with a yellow spot biomicroscopically. With progressive traction, a small foveal dehiscence occurs and is associated with the development of a preretinal glial membrane (probably an attempted reparative response). The dehiscence is usually not visible beneath the membrane and is termed “occult”. This stage 1b lesion is characterised by the appearance of a yellow ring at the fovea, which is thought to represent displaced xanthophyll at the edges of the occult hole. Recent data from optical coherence tomography have shown that some stage 1a lesions may actually represent a foveal cyst rather than a full thickness foveal detachment.

Subsequently, a dehiscence occurs in the membrane itself and this extends either in a centric or pericentric (“canopener”) fashion, termed stage 2. Only about 50% of stage 1 lesions progress to stage 2, with the remainder either arresting or resolving, usually due to the release of traction as a result of localised vitreofoveal separation. In 80% of stage 2 lesions, localised vitreofoveal separation occurs with the formation of an operculum (visible in about 80% of lesions), which remains attached to the separated posterior vitreous cortex at the fovea (stage 3), while the remainder (20%) may arrest or resolve spontaneously. Approximately

20% of stage 3 lesions subsequently develop a full posterior vitreous detachment (stage 4). Although spontaneous

closure occurs in approximately 20% of stage 2 lesions, it is much rarer for this to happen in stage 3 (7%) and 4 (<1%)

lesions.4

The description of the pathophysiology of macular hole formation has led to the evolution of surgical treatments for the condition using modern vitrectomy and posterior segment techniques. The evidence for the effectiveness of these techniques is summarised below.

Question

Is surgical treatment effective in preventing progression of stage 1 (impending) lesions?

The evidence

In the late 1980s and early 1990s, a number of investigators evaluated the benefit of vitrectomy and posterior vitreous cortex (PVC) removal in stage 1 lesions in an attempt to prevent FTMH formation by removing vitreous traction. The procedure consisted of a three-port pars plana vitrectomy and PVC separation without the use of intraocular gas tamponade. Initial results from uncontrolled pilot studies appeared favourable, with a rate of progression to stage 2 of 20% in operated eyes.5,6

However, a randomised trial that included a no-treatment group, revealed a progression rate of 37% in the surgical group compared to 40% in the observation group and showed no statistical benefit in terms of vision.7–9 Full recruitment to the study could not be completed and no definitive recommendations could be offered. In the light of these data and in view of the favourable surgical results achieved for FTMH, impending holes are rarely treated.

Question

Is surgery effective in achieving anatomical closure and vision improvement in stage 2, 3 and 4 FTMH?

The evidence

Kelly and Wendel were the first to report successful surgical closure of FTMH.10,11 In their initial report,6 using vitrectomy, PVC separation, epiretinal membrane (ERM) dissection and intraocular gas tamponade, anatomical closure was achieved in 58% of eyes, with visual improvement in 42%. A number of subsequent case-control series11–13 demonstrated improved outcomes, which led to a prospective randomised controlled trial conducted by the Vitrectomy for Treatment of Macular Hole Study Group.15–17 The results were difficult to interpret and showed only a marginal benefit in vision and a relatively high rate of sight-threatening complications in the treated group compared to the observation eyes. A number of confounding factors, in terms of study design, are thought to account for these results. First, the surgery was performed by a large number of surgeons, with different levels of expertise, in a wide range of centres. Second, patients undergoing vitrectomy were precluded from having cataract surgery afterwards, and with visual results being reported at only six months after macular hole surgery, it is highly likely that the visual benefit was masked. It is generally agreed that further trials are required to evaluate the exact visual benefit of macular hole surgery.18,19

Question

Does the use of intraoperative adjunctive substances improve the results of FTMH surgery?

membrane dissection, which produced impressive results in uncontrolled case series but which were less successful with recombinant TGF-β .23,24

Liggett et al. reported the use of autologous serum as an adjunct in a small pilot study, achieving a closure rate comparable to that achieved with bovine TGF-β 2.25 This substance has also been shown to stimulate proliferation and migration of glia, retinal pigment epithelial (RPE) cells and fibroblasts, and to facilitate chorioretinal adhesion in animal models.26 Initial reports from uncontrolled studies using autologous serum have proved encouraging with closure rates of about 70%.27 More recently, the Vitrectomy for Treatment of Macular Hole Study Group reported nonrandomised data on vitrectomy plus autologous serum versus vitrectomy alone and found no difference in results between the two groups.28

Autologous platelet concentrates, which are also potent stimulants of cellular migration and proliferation,29,30 have been shown to be promising31–33 with closure rates of 95%.31,32 Other substances that have been evaluated as adjuncts include autologous plasma–thrombin mixture,34 autologous fibrin,35 Tissucol36 and bovine thrombin.37 Although all these substances have shown encouraging early results, they await further evaluation in properly designed trials.

Question

Is reoperation effective in eyes with persistent FTMH after primary surgery?

The evidence

The demonstration by histological studies that successfully sealed holes are closed or “bridged” by glial cells led a number of investigators to examine the possibility of encouraging postoperative healing with the use of substances that stimulate glial activation and migration. The rationale and potential advantages of such substances appear attractive for a number of reasons. First, they might enhance the closure rate in less favourable cases, such as stage 3 and 4 holes. Second, they might obviate the need to perform intraoperative ERM dissection, which can prove difficult in some cases where the membranes are very nebulous. Third, they might obviate the need for patients to posture in the postoperative period. Potential disadvantages include cost, prolongation of the procedure risking intraocular infection, and stimulation of an over-aggressive glial response postoperatively, leading to ERM formation and traction around the edges of the hole.

In 1992, Glaser reported the use of bovine transforming growth factor-β 2 (TGF-β 2),20–22 with or without epiretinal

The evidence

There are no randomised controlled trials addressing this issue, but given that the failure rate may be as high as 20%, reoperation is often considered. Three case series have specifically reported the outcome of reoperation after unsuccessful primary surgery with anatomical success rates of 80–90%38–40 with significant visual improvement of two Snellen lines in over 60% of eyes,39 but this effect may be exaggerated and better quality trial data are required.

Question

What are the complications of FTMH surgery?

The evidence

Although patients undergoing FTMH surgery may develop general complications related to closed intraocular

surgery, a number of complications specific to macular hole surgery have been reported although generally these are rarely sight-threatening.2–73 Early postoperative complications include problems related to posturing, such as neck and back discomfort. These should be anticipated preoperatively, particularly in the elderly, who may have osteoarthritis of the neck. Some patients have developed ulnar nerve compression syndromes due to prolonged pressure on the elbows during posturing.41 For these reasons, a number of investigators have examined whether surgery with less rigorous or no posturing is feasible and have reported case series with good surgical results.42,43

Another early complication is intraocular pressure elevation. This is usually secondary to postoperative gas expansion and is usually transient,24 responding rapidly to medical treatment. Gas overfill and angle closure can occur.

Postoperative sterile hypopyon has also been noted in some cases, particularly with the use of adjuncts.37 The possibility of infection needs to be excluded in these cases.

Other complications include retinal tears (3%)44 and detachments (1·8–14%),44–46 RPE damage or phototoxicity (1–3%)44,45,47,48 and glaucoma.49 A number of reports have described the occurrence of non-progressive peripheral, absolute, wedge-shaped field defects after apparently uncomplicated surgery.50–59 Nerve fibre layer damage during separation of the PVC and/or air drying have been postulated as possible mechanisms.

Longer term complications have also been reported. Hole persistence, after failed surgery (in 5–30% of cases), is associated with enlargement of the hole diameter and further decline in acuity.60 For these cases, reoperation should be considered.61–63 Late reopening of the hole after successful surgery has also been reported (<10% of cases)64–68 and these are also amenable to reoperation. The mechanism of reopening may be related to foveal stress due either to ERM contraction or cystoid oedema, particularly after cataract extraction, although in the majority of cases no specific cause can be identified.

The most common long-term complication is nuclear cataract after surgery, and like nucleosclerosis after vitrectomy for ERM peeling,69 it may occur in up to 80% of patients at two years70 with 25% requiring extraction.10,14 Simultaneous macular hole and cataract surgery, particularly with modern phacoemulsification, may be considered in some cases.42,71,72 Combining these procedures may be associated with increased risk of postoperative pseudophakic cystoid macular oedema72 and late reopening.

In view of the frequency of nuclear cataract progression, hole persistence or reopening and other complications, patients should be warned of the possibility of requiring reoperation and/or cataract surgery after macular hole surgery and other complications. Further clinical data from ongoing prospective trials will provide greater

understanding of the benefits and risks of macular hole surgery. Future developments such as enzyme-assisted vitrectomy73 may allow atraumatic separation of the PVC and reduce the incidence of complications.

New developments in macular hole surgery

Despite the plethora of adjunctive substances that have undergone only preliminary evaluation, researchers continue to report ever-increasing surgical success rates using vitrectomy without adjuncts, emphasising the importance of patient selection (hole size and shorter duration). Some have questioned the absolute necessity of using longer acting gases and prone posturing although further randomised data evaluating these variables is required. In addition, a number of surgical refinements have been introduced, including internal limiting membrane (ILM) peeling74–77 with or without the use of dyes such as indocyanine green,78 to enhance visualisation of the ILM. Although initial non-randomised studies have demonstrated encouraging results,74,75,77,79 prompting many clinicians to adopt ILM peeling, others have failed to show any improvement in success rates.80,81 Clearly, further data from randomised studies are required.

Conclusions and recommendations

Over the past decade, macular hole surgery has continued to develop rapidly. Although intraoperative adjuncts showed early promise, clinical data have failed to demonstrate significant positive statistical effects for the majority of agents. The improvement in surgical success rates in recent years has been attributable predominantly to improved surgical techniques and preoperative case selection rather than the use of adjuncts. The use of ILM peeling ensures complete removal of the scaffold and glial elements from around the hole, and although its precise role remains to be determined some anecdotal data suggest that it may be useful for larger or more chronic lesions. Further prospective randomised clinical studies are required to evaluate its role, although given the rapid evolution of surgical techniques and the already high (>90%) anatomical success rates in most studies, these will be difficult to carry out.

References

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