Most MHs occur in eyes with no previous pathology (‘idiopathic’). The patient generally complains of acute or subacute decrease in both far and near visual acuity (VA), ± metamorphopsia and/or micropsia, ± positive or negative scotoma. Five percent of patients are asymptomatic ⁷. The visual loss caused by MH is variable. VA decreases gradually with time, and after several months of evolution it is usually around 0.1. In a series of unoperated MHs, more than 80% of eyes had a VA between 0.1 and 0.05 after 5 years of follow-up⁸. In practice, the VA of an eye with a full-thickness MH is usually less than 0.5 (typically 0.2). Patients rarely identify a central scotoma, but fairly frequently report what is indicative of a negative microscotoma (i.e. the disappearance of a letter from a word). The distortion or constriction of images and words is also reported.

At fundus biomicroscopy, the MH appears as a round full-thickness defect with sharp edges located at the center of the fovea. The size of the hole varies and tends to increase with time ⁸^–¹⁰. The surrounding retina is usually thickened by edema and microcysts, and is slightly detached from the retinal pigment epithelium (RPE). In half the cases, 1–15 yellow deposits are present on the exposed RPE. An operculum may also be found in front of the hole. It is generally smaller than the hole, usually round but sometimes irregular in shape, translucent, discreetly yellow, and slightly mobile with eye movements. An epiretinal membrane may also be present around the hole. It appears as a discreet reflection, usually with no wrinkling of the internal limiting membrane (ILM). The prevalence of epiretinal membranes is higher in long-standing MHs¹¹^–¹³. Posterior vitreous detachment may vary, from incomplete separation of the vitreous from the macula to a vitreous completely detached from the macula and even from the disc^3,⁴.

OCT allows a reliable diagnosis of MHs by confirming the existence of a full-thickness opening in the center of the fovea with no interposition of tissue between the vitreous cavity and the RPE. OCT also clearly differentiates full-thickness MHs from lamellar or pseudo-holes, shows the stage of MH, measures its diameter, and provides information regarding the risk of developing a MH in the fellow eye. No other ancillary testing is mandatory. Fundus photographs can be used as archive. Fundus autofluorescence images and fluorescein angiography are not of great interest for MHs. The defect is usually hyperautofluorescent and after fluorescein injection shows a discrete early hyperfluorescence. The surface area of fluorescence does not increase during angiography and its intensity decreases at later phases with no dye diffusion (Fig. 66.1)^14,¹⁵.

Fig. 66.1 Full thickness macular holes as they are seen (from top to bottom) by color, red-free and blue filter fundus photographs (note an epiretinal membrane appearing as a clearer area on the blue filter photograph); fundus auto-fluorescence (hyper-autofluorescence of the hole) and fluorescein angiography (central hyperfluorescence).

Differential diagnosis

Without OCT, MHs might be misdiagnosed. With OCT, the differential diagnosis is very reliable. Unlike a full-thickness MH, in a macular lamellar or pseudohole there is an interposition of retinal tissue between the vitreous cavity and RPE on OCT scans. Lamellar holes, usually due to an aborted process of MH formation, are characterized by thinning of the base of the foveal center, and normal thickness of the foveal edge that presents a cleft between its inner and outer retina ¹⁶. Pseudoholes are due to tangential retraction of an epiretinal membrane that thickens the foveal edge with a normal or thin foveal center¹⁶.

Impending MHs

In most cases, early stage MHs are foveal cysts ^3,⁴. VA in these cases is usually normal or above 0.5. The macula may look normal on fundus biomicroscopy, or else an outer central yellow spot may be present, combined with a flattened foveal pit and foveolar radial striae¹⁷. In more advanced cases, outer MHs, the foveola has a cystic appearance, with radial striae. An outer yellow ring is present¹⁷.

Secondary MHs

Post-traumatic MHs mostly occur in young males. Traumatic MH is due to a violent deformation of the eyeball, which results in rupture of the fovea ^18,¹⁹. The vitreous remains completely attached to the retinal surface. The profile of the traumatic hole is not different from that of the idiopathic hole, except in cases in which the retina is thinner than normal at the hole edge due to post-traumatic atrophy of the pigment epithelium. Indeed, in some cases, these MH may be associated with a break in Bruch’s membrane or an area of pigment epithelium atrophy at the posterior pole, which on OCT scans corresponds to retinal thinning and to a deep scotoma in the visual field. If the lesion involves the foveal center, there is a risk that vision will not improve, even if the MH is closed.

In about 10% of highly myopic eyes, OCT reveals the presence of a MH in the staphyloma, which causes moderate loss of vision and is not seen on biomicroscopy. In eyes with high myopia, an MH may also occur after a long evolution of a myopic foveoschisis, especially when it is complicated by foveal detachment ²⁰.

Vitreomacular traction syndrome, as described in the previous chapter, may worsen and lead to an MH. The frontier between these cases and an impending MH is not clearly delimited.

Very occasionally, other conditions may also give rise to an MH by causing atrophy of the foveal center. For example, in group 2 macular telangiectasis the foveal center tends to become more atrophic with time. In some cases the process may result in an MH. Adult-onset pseudovitelliform dystrophy may also sometimes result in significant thinning of the foveal center in front of the subretinal deposit. In rare cases this thinning evolves into an atrophic MH, an evolution that coincides with the disappearance of the deposit. MHs may also occur in Best’s disease.

Anatomical considerations

Before OCT became available, Gass classified MHs into several stages on the basis of fundus biomicrospy. Later he revised his classification. This revised classification is still in use and is summarized in Box 66.1. Mainly on the basis of OCT examination of MHs and their relationship with posterior vitreous detachment, Gaudric et al. and Haouchine et al. gave the description of the different steps in MH formation and evolution (Fig. 66.2)^3,⁴. Gaudric’s description of MHs is also used as a system of classification mainly based on OCT. In this classification the size of the MH is indicated separately. The information provided by Gaudric’s classification is more accurate.

Box 66.1

Gass’s revised classification of macular holes

• Stage 1: Either a yellow spot (stage 1A) or a yellow ring (stage 1B) in the fovea

• Stage 2: The first biomicroscopically identifiable full-thickness retinal defect (sometimes masked by the overlying pseudo-operculum) and having a diameter less than 400 µm

• Stage 3: Having a diameter of 400 µm or more, and usually with a partial vitreomacular separation

• Stage 4: Complete separation of the vitreous from the entire macular surface and optic disc

Fig. 66.2 Gaudric and Haouchine’s description of macular hole (MH) formation with OCT. Color fundus photographs show (from top to bottom) stage 1A, 1B impending MH and a full thickness MH. OCT scans from top to bottom:

• Stage 1A: Impending MH: a central hyporeflective cyst develops in the inner portion of the foveal center, resulting in the elevation of the foveal floor. The outer retinal layer remains intact. The posterior hyaloid is variously detached from the macular surface, exhibiting a biconvex appearance on scan profiles. It adheres to the top of the foveal cyst.

• Stage 1B: Impending MH, or outer MH: the central cyst opens the outer retinal layer (occult MH). The posterior hyaloid remains attached to the roof of the foveal cyst.

• Stage 2: Full-thickness MH: incompletely detached operculum and posterior hyaloid adherence to the operculum persists.

• Stage 3: The posterior hyaloid is completely separated from the macular surface but remains attached to the optic disc (the Weiss ring is not detached). It is only slightly detached from the retinal surface, and usually remains visible on OCT scan profiles.

• Stage 4: Full-thickness MH: The main difference between stage 4 and stage 3 MHs is that in stage 4, posterior vitreous detachment (PVD) is complete, with a Weiss ring that is mobile in the vitreous cavity on biomicroscopy (the posterior hyaloid and operculum are out of focus on OCT retinal scans).

Gaudric’s OCT based description of MHs is also used as a system of. In this classification the size of the MH is indicated separately. Then this classification differs from Gass’s revised classification for stage 2 and 3 MHs: for example, a MH 350 µm in diameter that has completely separated the posterior hyaloid from the macular surface is a stage 2 MH according to Gass and a 350 µm stage 3 MH according to Gaudric.

Another useful anatomical consideration concerns the ILM (the basement membrane of the Müller cells) as it may be peeled during MH surgery. The ILM is thinnest at the fovea and the disc (0.01–0.10 µm). Whereas the inner vitreal surface of the ILM is smooth, its outer retinal surface is rough and undulated. If ILM peeling is decided upon, it is necessary to surgically dissect the retinal surface of the ILM from the footplates of Müller cells.

Fundamental principles

Since the first description of MH surgery, the surgical technique is based on vitrectomy with posterior vitreous detachment, peeling of any epimacular membrane, thorough fluid–gas exchange, and postoperative face-down positioning of the patient ^1,²¹. However, many variants of this technique have been proposed. The use of several adjuvants, including TGF_β2, autologous serum, or autologous platelets, has been proposed to increase the success rate, without becoming widespread^22,²³. The peeling of the ILM has become popular for the same purpose, especially since it has been facilitated with the use of visualizing agents, even without being proved useful for all MH (Clip 8.5). Different types of tamponade are now used and the dogma of face-down positioning for all MHs is challenged.

Clip 8.5 Peeling of the posterior hyaloid, an epiretinal membrane found around a macular hole and internal limiting peeling after staining with brilliant blue (see text for more details).

The main principle behind posterior vitreous cortex removal followed by extensive vitrectomy is to make room for a large gas bubble. Derived from OCT findings, the release of vitreous traction on the edge of the hole is only in some cases the other goal of vitrectomy.

The goal of epiretinal membrane and ILM peling is to release any tangential resistance to the closure of the MH.

The role of gas tamponade is to create contact of the gas bubble with the macula rapidly resulting in the flattening of the edematous edge of the hole, and the mechanical narrowing of the foveal defect. The necessary duration of the tamponade depends on the duration of the following healing process, which requires glial cell proliferation resulting in the formation of a small central foveal scar. The duration of this healing process seems to be different, depending on the size of the hole, varying from a few days to a few weeks ²⁴.

For the healing process, it perhaps does not matter if the patient’s head is in the face-down or vertical position, as the gas bubble acts more by isolating the retina from liquid intrusion than by its buoyancy. The goal of face-down positioning is to facilitate healing by prolonging the duration of the gas bubble tamponade when the bubble does not entirely fill the vitreous cavity.

Goals of surgery

The goal of MH surgery is to increase VA by closing the MH, i.e. by reducing its size as much as possible by flattening its edges and creating a small glial scar that fills the remaining gap and supports the center of the fovea ²⁵^–²⁷.

Indications for surgery

As impeding MHs have a chance of closing spontaneously, they are operated on only when, in rare cases, they remain unchanged for a long time and significantly impair vision.

Idiopathic full-thickness MHs usually remain open if they are not treated and cause great visual impairment after several years (VA between 0.1 and 0.05 in more than 80% of cases)⁸. They constitute an indication for surgery.

Rarely, very small holes (especially those with a diameter ≤250 µm) may close within a few weeks without surgery, even if the vitreous cortex is already detached ²⁸. Surgery for these very small MHs may therefore be delayed until up to 3 months after their appearance, to give them a chance to close spontaneously.

Very large MHs, usually long-standing holes, are considered to have a poor prognosis. However, in a series of selected very large MHs (>800 µm in diameter), the postoperative closure rate was reported to be higher than 70%, with an increase in the mean VA of closed holes (Surgical outcome of extra-large MHs. R. Tadayoni, M. Bennani, A. Gaudric, AAO 2007). Selected cases of very large MHs with no significant pigment epithelium alteration, even if they are long standing, may also benefit from surgery ^29,³⁰.

Traumatic MHs may close spontaneously in the first few months. Observation during this period may therefore be the preferred choice in the management of traumatic MHs ^31,³². If such holes are still open after this period, surgery can close them in most cases. In myopic eyes, many of the MHs incidentally detected by OCT are asymptomatic and do not need surgery. Symptomatic holes can benefit from surgery. MHs secondary to central retinal atrophy of various etiologies have a poor postoperative prognosis and may not constitute good indications for surgery.

Preoperative assessment

Preoperative assessment of a patient presenting with a MH includes a complete examination of both eyes including fundus biomicroscopy and also OCT examination of the macula and posterior hyaloid. Of particular interest are: whether the vitreous is completely detached (Weiss’s ring), size of the MH (Fig. 66.3), and the possible presence of an epiretinal membrane.

Fig. 66.3 The size of a macular hole (aperture diameter) can easily be measured on OCT scans. Care should be taken to pass through the center of the macular hole so as not to underestimate its size.

Other significant pathology such as a cataract, glaucoma, and peripheral retinal lesions predisposing to retinal detachment should also be noted.

Examination of the fellow eye provides information about their risk of a MH, which is around 10%. Fellow eyes whose posterior hyaloid is already detached from the macular area are not at risk for developing a MH, even if the hyaloid remains attached to the optic disc and the periphery of the posterior pole ³³. OCT makes it possible to diagnose such premacular posterior vitreous detachment, which cannot be detected by biomicroscopy alone. When, on the other hand, part of the posterior hyaloid remains attached to the foveal center, the risk of MH remains³⁴. However, in some cases, spectral domain (SD) OCT shows very subtle changes in the shape of the foveal pit at the junction between the posterior hyaloid and the ILM, due to vitreous traction. In individuals whose fellow eyes already exhibit an MH, this may constitute a risk of MH.

Anesthesia

MH surgery is usually performed under local anesthesia. If general anesthesia is necessary, the anesthesiologist should be informed regarding the intraocular gas injection, to avoid the use of anesthetic gases that diffuse to the vitreous cavity and expand the intraocular gas bubble.

Operation techniques

Surgery includes vitrectomy (with posterior vitreous detachment if necessary), peeling of any epimacular membrane, peeling of the ILM, at least for large MHs, a careful search for any retinal break, and fluid–air and air–gas exchange.

Vitrectomy

MH surgery is a suitable indication for transconjunctival sutureless vitrectomy (23- or 25-gauge). When using sutureless vitrectomy one should indeed make sure that the incisions are not leaking. Any such leakage reduces the size of the gas bubble and may adversely affect the tamponade, thus diminishing the chance of MH closure.

Vitrectomy begins with core vitrectomy. In stage 4 MH, vitrectomy is easily completed. Extensive vitrectomy, up to the vitreous base, is needed to make as much room as possible for the gas bubble. At earlier MH stages, the vitreous is not completely detached and vitreous cortex removal will be needed before extending the vitrectomy. The easiest way to remove the vitreous cortex from the retinal surface is to start by detaching the Weiss’s ring from the optic disc. Different instruments may be used, including the vitreous probe itself. The new 23/25 G vitreous probes, with their aspirating port close to the tip of the probe, are especially effective for pulling on the vitreous and detaching it from the optic disc. The tip of the probe can be accurately positioned in the disc cup with the aspirating port oriented nasally, because the vitreous cortex is more firmly attached on that side of the disc. Once this attachment is broken the entire Weiss’s ring is detached, and it is easy to lift up the entire vitreous cortex, which often contains the pre-foveolar operculum. During this maneuver one can see the centrifugal progress of the vitreous cortex detachment up to the equator. Some surgeons use visualizing agents such as triamcinolone to obtain a clearer view of the vitreous and the posterior vitreous detachment.

Peeling

In about 30% of cases there is an epiretinal membrane around the hole. Membranes are more frequent in stage 4 and large MHs ^11,³⁵. They are not contractile like idiopathic epiretinal membranes: they are composed of vitreous collagen and a few cellular elements, especially fibroblasts. As they are soft and friable, it is easier to remove them, for example by gently brushing the retinal surface from the outside to the MH edge, with either the soft tip of a back-flush cannula or with a soft retinal scraper, rather than trying to remove them with forceps. These membranes often adhere firmly to the hole edge, in which case they can be cut with the vitreous probe.

ILM peeling is currently performed in MH surgery, although one should bear in mind that at least 80% of all MHs and about 95% of small MHs (up to 400 µm in diameter) can be closed without ILM peeling ^36,³⁷. Discrete damage to the nerve fiber layer and small but asymptomatic paracentral scotomata detected during microperimetry after MH surgery with ILM peeling have been reported^38,³⁹. For small MHs, ILM peeling is not mandatory³⁶. However, several studies suggest that ILM peeling increases the success rate of MH surgery, at least for large MHs (>400 µm) (Internal limiting membrane peeling for large macular holes: a randomized, multicentric, and controlled clinical trial. R. Tadayoni R et al. ARVO 2009)^36,^40,⁴¹. Several techniques, using forceps or scrapers, are used to peel the ILM. Peeling usually begins a small distance away from the hole edge, where the ILM is thicker and less adherent. It is then dissected about 1 mm all round the hole (see also Clip 8.5).

ILM peeling can be difficult to perform. The use of visualizing agents facilitates this tricky surgical maneuver and makes it easier to control.

Gas filling

The role of gas tamponade is to create the conditions for the healing of the MH by isolating the MH from liquid intrusion. There is still no consensus of opinion regarding the type of tamponade that should be used: air, SF6, C2F6, C3F8, and even silicone oil have all been proposed. The choice of tamponade may affect the success rate, especially in the absence of strict face-down positioning. Air or 20% SF6–air cover the macula in the upright position for a few days, but this may not be long enough in some cases (e.g. larger holes). Seventeen percent C2F6 and 15% C3F8–air (percentages are given as an indication as there is no consensus) isolate the macula from liquid infiltration for more than 1 week, even when the head is in the upright position, but are completely resorbed only after more than 1 month. These estimations of duration may also change, depending on various parameters such as the extent of vitrectomy, the attention given to the fluid–gas exchange, and the tightness of sclerotomies.

Intraoperative complications

The most common intraoperative complication of MH surgery is an iatrogenic retinal break. Despite continuous progress in vitrectomy techniques, this risk has not been re-evaluated since the 1990s, when it was found to be around 5%^42,⁴³. It warrants careful examination of the retinal periphery before the injection of gas, in order to detect and treat any breaks.

Postoperative care

The postoperative care after MH surgery is similar to that of all vitrectomies with gas injection. Antibiotics, anti-inflammatory drops, and drops to dilate the pupil are commonly prescribed. Gas bubbles necessitate monitoring of intraocular pressure to treat elevation of pressure that may occur. Air travel is forbidden, as is climbing more than about 1000–1200 m over the level of where the surgery was done, as these can increase the intraocular pressure due to a rapid expansion of the gas.

For the patient, the most difficult part of MH surgery is the postoperative positioning. There is no consensus about the duration of face-down positioning. The most common practice is to encourage the patient to remain face-down, as much as possible for 1 week. Several proposals have been made to ease this positioning. However, only two randomized series have so far been carried out in this respect. One showed a significant reduction of the success rate without face-down positioning, but a post hoc analysis of this study suggested that the reduction was significant only for MH > 400 µm and not in smaller holes ⁴⁴. The other study, which only considered only idiopathic MHs ≤400 µm in diameter, demonstrated that after surgery for these small MHs a strategy that did not impose the face-down positioning was not inferior to face-down positioning (confidence interval for closure rate reduction: 0 to 14.88%, with a 5% risk of error)³⁷. In this study, the patient had a large (>90%) bubble of C2F6 and avoided the supine position for 10 days. The results may not apply to patients treated with a small volume of non-lasting postoperative bubble gases or to patients with full freedom of positioning, including the supine position. Consequently, depending on the size of the hole, and the surgical technique (in particular, the type of gas used, and the actual size of the bubble), one can choose from different strategies, taking into account on the one hand the painfulness of face-down positioning (and also a small risk of complications like thrombophlebitis and pulmonary embolism or ulnar nerve palsies) and, on the other hand, the need to tamponade the fovea during the time necessary for a scar to form in a closed MH.

Postoperative complications

The most serious postoperative complication is retinal detachment, which may occur within days or weeks after the operation. Estimates of its frequency vary from 1 to 14%^21,⁴³. Today, with better fluidics and operational precautions, the rate of retinal detachment should remain below 3%. However, it remains mandatory to detect these detachments carefully as soon as possible as the gas bubble prevents some patients from noticing visual symptoms.

The occurrence of a cataract after MH surgery is common ^45,⁴⁶. Patients should be aware that, in most cases, cataract surgery becomes necessary 1–2 years after MH surgery. For some surgeons this justifies combining MH surgery with cataract surgery at the same operating time.

Reopening of the MH may occur up to more than 6 years after surgery. However, most reopenings occur during the first 2 years (approximately the mean and median values for the time from surgery to reopening)⁴⁷. Rates of reopening vary considerably in the literature, from 0 to 25%, with a mean of about 6%. The real cause of reopening is still not known. Recently, its incidence seems to have decreased, corresponding to a concomitant increase in the success rate of MH surgery. Some authors believe this is connected with the improvement in surgery, including ILM peeling^47,⁴⁸. A reopened MH can be operated on in the same way as for initial surgery, with similar positive results⁴⁹.