17 Macular Holes
Gass stimulated interest in macular holes with his theory that tangential traction played a role in the development of macular holes. 1 The development of vitreoretinal surgical techniques for macular holes has allowed a majority of eyes to achieve successful closure of the hole with visual improvement. The landmark report by Kelly and Wendel 2 first demonstrated that vitrectomy with removal of the posterior cortical vitreous and injection of an intraocular gas bubble could be used to close macular holes (anatomic success) and improve visual acuity (functional success). Their report has stimulated much additional research and refinements in the techniques of macular hole surgery.
Visual improvement following successful treatment of macular holes led to a reevaluation of the etiology of visual loss in eyes with macular holes. It was realized that visual loss was not caused by irretrievable loss of photoreceptors but rather by dehiscence in the fovea with neurosensory detachment surrounding the macular hole. 3 , 4 , 5 This was confirmed using scanning laser microperimetry, which demonstrated that closure of the macular hole resulted in disappearance of the absolute scotoma and improved visual function of the photoreceptors within the area of the neurosensory retinal detachment. 3 The goal of macular hole surgery was to close the macular hole and cause the neurosensory retinal detachment to resolve. Successful closure of the macular hole and elimination of the intraretinal cystic changes near the edge of the macular hole and subretinal fluid around the edges of the macular hole led to visual improvement.
17.2 Clinical Features and Pathophysiology
In one study, the incidence of macular holes was reported to be 7.8 persons and 8.69 eyes per 100,000 population per year eyes in Olmsted County, Minnesota, which is predominantly Caucasian. 6 Macular holes have been reported to occur about 2 to 3 times more frequently in women compared to men in surgical series reports 7 , 8 and 3.3 times more frequently in women compared to men in a population-based study. 4 Idiopathic macular holes typically develop in the seventh or eighth decade of life. The mean age of patients with myopic macular holes is younger, and it is much younger in patients with traumatic macular hole due to increased incidence of ocular trauma in young individuals. The cause of the gender difference is unknown, although there may be anatomic variability between men and women with respect to the firmness of attachment of the collagen fibrils of the posterior hyaloid with the fovea. A macular hole develops in the fellow eye in about 7 to 12% of patients with macular holes. 6 , 9 Patients with macular holes usually report some degree of decreased vision or metamorphopsia. Patients note central scotomas much less frequently. Often, symptoms are first noticed when the patient incidentally covers the fellow eye. Approximately one-half of untreated eyes with macular holes have progressive loss of visual acuity by two or more lines in eyes followed up for <3 years, 4 to 5 years, and >6 years. 9
The diagnosis of macular hole is usually straightforward. It may be identified on examination of the macula with a contact lens or hand-held indirect lens (e.g., 78-diopter lens) in conjunction with slit-lamp biomicroscopy. A fully developed macular hole appears as a dark, round defect in the fovea that is typically surrounded by a small cuff of neurosensory retinal detachment (Fig. 17-1). Small, yellow dots are sometimes present in the center of the hole at the level of the retinal pigment epithelium (RPE). Prehole opacities (pseudo-opercula) may be present depending on the stage of the hole, as described later. The accuracy of diagnosing a macular hole is reasonably high with slit-lamp biomicroscopy but optical coherence tomography (OCT) has become an essential tool to confirm the diagnosis of a full-thickness macular hole.
The development of macular holes has been divided into four stages by Gass. 1 , 10 His classification helped to define the role of the vitreous in the pathophysiology of macular holes and appears to correlate well with clinical observations of macular holes, even though he did not have the benefit of OCT, which has helped to further refine our understanding of the pathophysiology of macular holes. Macular hole development is related primarily to tangential contraction of attached, prefoveolar cortical vitreous. This traction ultimately causes a break or dehiscence to occur at the umbo, the thinnest and weakest portion of the retina, and subsequent centrifugal movement of the foveolar tissue. Subsequent to Gass’s publication, the importance of a perimacular posterior vitreous detachment was recognized by Spaide et al and Gaudric et al using early OCT imaging. 11 , 12 The localized vitreous separation around the fovea can lead to additional traction with ocular movements that helps to create the foveal dehiscence as the vitreous is inserted obliquely at the perimeter of the fovea where it can exert additional traction. The presumed sequence of events is illustrated in Fig. 17-2, Fig. 17-3, and Fig. 17-4, and the specific clinical features of each stage are as follows.
17.2.1 Stage 1 Macular Hole
Stage 1 macular hole is characterized by a yellow spot (stage 1A) or yellow ring (stage 1B), which is believed to represent a focal elevation of the fovea caused by tangential vitreous traction. Stage 1 macular holes do not represent true macular holes in that there is no dehiscence of the foveal photoreceptors. A few eyes with stage 1 macular hole have spontaneous separation of the posterior hyaloid from the macula and return to normal, although they most probably progress to stage 2 macular holes. Stage 1 macular holes are generally short-lived (lasting perhaps several weeks) and often minimally symptomatic, so they are only occasionally recognized clinically (Fig. 17-2a) but can be recognized easily with OCT (Fig. 17-2b).
17.2.2 Stage 2 Macular Holes
Stage 2 macular holes have a small central or arcuate perifoveal dehiscence (Fig. 17-3a). Soon thereafter, a small cuff of surrounding neurosensory retinal detachment develops around the foveal dehiscence. Some eyes with stage 2 macular holes have a flap overlying the macular hole that can make the macular hole difficult to recognize with slit-lamp biomicroscopy alone; they are best seen with OCT (Fig. 17-3b). The stage 2 macular hole enlarges gradually to form a stage 3 macular hole.
17.2.3 Stage 3 Macular Holes
Stage 3 macular holes are typically 400 µm or larger, and the posterior hyaloid/cortical vitreous is still attached around the fovea (Fig. 17-4a, b). Some eyes may have persistence of a stage 3 macular hole for many months or even years. Some, but not all, eyes progress to stage 4 macular holes.
17.2.4 Stage 4 Macular Holes
Stage 4 macular holes differ from stage 3 holes only in that the posterior hyaloid has separated completely from the macula and optic nerve. Thus, a Weiss ring is present at this stage. Spectral-domain OCT has shown that most stage 3 macular holes have a perimacular posterior vitreous detachment; therefore, stage 4 macular holes are best described as eyes with a complete posterior vitreous detachment (Fig. 17-5).
The “operculum” associated with some stage 3 and 4 macular holes appears to represent a pseudo-operculum, as it does not appear to contain photoreceptors. 13 There are reports of spontaneous closure of stage 2 and 3 macular holes, but this event is uncommon. 14 , 15 Most eyes with macular holes show progressive deterioration in visual acuity until the acuity stabilizes between 20/100 and 20/400. An updated classification system for vitreomacular traction and macular holes has been developed, and this is more useful in evaluating the surgical and visual acuity results than the Gass classification system. An updated classification scheme for macular holes has been proposed. 16 Macular holes are classified by size: small (=250 µm) (Fig. 17-6a), medium (>250 to =400 µm) (Fig. 17-6b), and large (>400 µm) (Fig. 17-6c). Eyes are also classified by whether or not there is vitreous traction to the edges of the macular hole and whether the macular hole is primary or secondary. 16 Secondary macular holes include such causes as traumatic macular holes, myopic macular holes, macular holes secondary to choroidal neovascularization, macular schisis, and cystoid macular edema (CME).
Although OCT has become the standard method to confirm the diagnosis of a macular hole, several ancillary techniques also suggest the presence of a full-thickness macular hole (stage 2, 3, or 4). During biomicroscopic examination of the macula, a narrow slit beam of light can be directed at the hole. When asked to look at the beam, a patient with a full-thickness macular hole should typically report a break or focal constriction in the slit (“positive slit beam” or Watzke–Allen sign). Similarly, the hole can be demonstrated with a laser aiming beam of about 50 µm in size. When the beam is placed within the hole, the patient should not be able to see the beam (“positive laser beam” sign). Fluorescein angiography can also be useful diagnostically. With a macular hole, there is usually a central round window defect corresponding to the size of the hole. There may also be a rim of hypofluorescence around the hole representing the cuff of neurosensory detachment around the hole (Fig. 17-7).
17.3 Differential Diagnosis
The most common condition that mimics a macular hole is a macular pseudohole resulting from an epiretinal membrane or a lamellar macular hole. 17 The epiretinal membrane creates a white-yellow sheen surrounding the fovea, which makes the fovea appear dark like a macular hole (Fig. 17-8a). OCT images of lamellar macular holes show thinning of the central fovea often with an epiretinal membrane causing thickening of the perifoveal retina (Fig. 17-8b). Unless the macular distortion from the epiretinal membrane is severe, eyes with macular pseudoholes typically have a visual acuity in the range of 20/20 to 20/40, which is much better than would be expected for a true macular hole of the same size. In addition, a cuff of subretinal fluid is absent with a pseudohole. One would also not expect a positive slit beam or laser aiming beam sign, as there is no dehiscence of foveal neurosensory tissue with the pseudohole.
OCT has become the primary way to distinguish macular holes from lamellar macular holes and macular pseudoholes. Fluorescein angiography can also help to differentiate macular holes from macular pseudoholes/lamellar macular holes. Macular pseudoholes/lamellar macular holes usually lack the central, well-defined window defect corresponding to the defect in the neurosensory retina.
Several other macular pathologic entities can be confused with a macular hole. CME related to prior cataract surgery, retinal venous occlusive disease, or intraocular inflammation may mimic a macular hole when a prominent central cyst is present. OCT can easily distinguish a cyst from a hole, and fluorescein angiography will typically show diffuse leakage associated with macular edema. A small, round subfoveal hemorrhage related to choroidal neovascularization or Valsalva maneuver may resemble a macular hole. Subfoveal hemorrhages show up as localized areas of increased reflectivity on OCT and block fluorescence on fluorescein angiography, which readily differentiates them from a macular hole. The cherry-red spot associated with a central retinal artery occlusion may be confused with a macular hole. The visual acuity is much worse in eyes with a central retinal artery occlusion than would be expected in eyes with a macular hole. OCT will show increased reflectivity in the superficial retina from inner retinal ischemia and the absence of a central full-thickness defect.
OCT is essential in correctly diagnosing macular holes and distinguishing them from other macular diseases that may resemble macular holes.
17.4 Management and Course
17.4.1 Preoperative Considerations
In considering treatment, it is useful to subdivide macular holes into several categories based primarily on the age and etiology of the hole, as indicated in Table 17-1. The best anatomic and visual prognosis occurs in eyes with recent-onset macular holes of 250 µm or less (these are typically less than 6 months in duration), as these eyes presumably have less damage to the foveal photoreceptors than do eyes with older macular holes. Some recent macular holes enlarge relatively rapidly to 300 to 500 µm, so the duration and size of the macular hole do not correlate precisely. This is why it is important for ophthalmologists and optometrists to recognize macular holes so they can be treated when they are of recent onset. Routine examination of the macula using slit-lamp biomicroscopy with a 78-diopter or contact lens is essential, as macular holes may be easily missed with indirect ophthalmoscopy only. Eyes with intermediate-duration macular holes (these are often 6–24 months in duration) still have a reasonably good prognosis and macular hole surgery is still indicated, but the visual results do not tend to be as good as in eyes with more recent macular holes. These macular holes are often in the range of 250 to 500 µm.
Chronic macular holes (more than 2 years’ duration) are more difficult to close, and the visual results tend to be less favorable. Chronic macular holes are usually large (greater than 500 µm), and they may have a round demarcation line at the border of the neurosensory detachment (Fig. 17-9a) or extensive RPE atrophy in the area of the cuff of subretinal fluid around the macular hole, which is best visualized with fluorescein angiography (Fig. 17-9b) and OCT (Fig. 17-9c). The decision whether or not to recommend vitreous surgery for an eye with a chronic macular hole is based on several factors, including the visual needs of the patient, status of the fellow eye, and estimated duration of the macular hole. The preoperative visual acuity of the patient and age of the macular hole, both of which are generally related to the size of the macular hole, are the most important prognostic factors for macular hole surgery. Macular holes older than 5 years can sometimes be closed successfully, but the visual acuity rarely improves substantially; therefore, in general, patients with such old macular holes should not receive surgery as most will not experience further decreases in visual acuity if nothing is done.
Persistent macular holes occur when the macular hole is noted to remain open soon after macular hole surgery has been performed. This usually represents primary failure of the macular hole to close and is noted when the intraocular gas bubble is small (less than 40%). Persistent macular holes may be missed unless the macula is examined by OCT 4 to 6 weeks following surgery. If the macular hole edges are visible after the gas bubble meniscus is above the macula, this is a strong suggestion that the macular hole has reopened, even if a neurosensory cuff has not yet formed. Recurrent macular holes are defined as cases in which the macular hole was definitely closed, as seen with OCT, after surgery, often with improvement in visual acuity. Recurrent macular holes may develop months to years following initially successful surgery. The causes of recurrent macular holes are variable and are associated most often with tangential traction from an epiretinal membrane in the macula but can occur after ocular trauma or cataract surgery complicated by postoperative CME. Repeat vitrectomy with removal of the epiretinal membrane/internal limiting membrane (ILM), if not removed previously, is generally the most effective treatment. There are reports of moderate success with fluid–gas exchange performed in the office, but this technique does not remove the source of tangential traction at the edge of the macular hole.
Macular holes may lead to an extensive retinal detachment in some eyes, especially those with high myopia. A peripheral retinal break must be ruled out, as many rhegmatogenous retinal detachments in eyes with macular holes actually result from a peripheral retinal break rather than the macular hole. Some of these macular holes are full-thickness macular holes and others are macular pseudoholes. When the macular hole is the cause of a large rhegmatogenous retinal detachment, then vitrectomy should be considered rather than a scleral buckle or pneumatic retinopexy to treat the retinal detachment. Traditional macular hole surgery is successful in treating these retinal detachments and macular holes in many eyes, but ancillary techniques such as macular buckle or long-term silicone oil tamponade can be considered to improve the success of closing the macular hole and treating the retinal detachment. Treatment of myopic macular holes with extensive retinal detachment will be discussed in more detail in the section “Myopic Macular Holes.” The visual results of macular hole surgery are less favorable in eyes with associated rhegmatogenous retinal detachment because there is more extensive damage to the macular photoreceptors. Some eyes with high myopia have myopic macular degeneration which may also limit the visual recovery.
Secondary macular holes are associated with other abnormal conditions that lead to foveal traction or stretching and subsequent macular hole formation. Vitreomacular adhesions with vitreomacular traction syndrome may lead to macular holes and have an excellent prognosis if the traction is relieved. Intravitreal ocriplasmin may be considered as an alternative to surgery when there is vitreous traction to the edge of a small (<400 µm) macular hole. 18 Trauma is a less common cause of macular hole but is important to recognize. Traumatic macular holes typically occur in boys and young male adults. The prognosis of vitreous surgery in eyes with traumatic macular holes is often determined by the extent of damage to macular RPE from the trauma. Traumatic macular holes have a higher rate of spontaneous closure compared to idiopathic macular holes, so it is best to wait 1 month after the trauma to see if the hole is closed on examination with OCT before considering vitreous surgery. Fluorescein angiography is a helpful tool to assess the extent of the traumatic macular damage, such as commotio retinae, choroidal rupture, and RPE atrophy. The results of vitreous surgery may be excellent in eyes with traumatic macular holes, so RPE atrophy and pigmentary changes in the macula should not be considered a contraindication to vitreous surgery (Fig. 17-10). Macular holes may also form in eyes with chronic CME, although most of these “holes” are actually large cysts. OCT is essential to distinguish between a large cyst and a full-thickness macular hole. Eyes with diabetic retinopathy and posterior hyaloid traction syndrome, traction retinal detachment, or epiretinal membranes also have an increased risk of developing macular holes due to traction on the fovea. For eyes with chronic CME and macular holes associated with diabetic retinopathy, the continuity of the ellipsoid layer and external limiting membrane (ELM) on OCT should be evaluated carefully before recommending surgery. Chronic damage to the macula from CME and diabetic retinopathy often limits the visual acuity improvement even if the macular holes are closed successfully.
17.4.2 Indications for Macular Hole Surgery
Functional criteria are very important in deciding whether or not to recommend macular hole surgery, as the patient measures the success of macular hole surgery by the improvement in vision rather than by the anatomic status of the macular hole (open or closed). Preoperative visual acuity is the most important prognostic factor for postoperative visual acuity in eyes with macular holes. Patients usually notice and complain of decreased vision by the time the visual acuity decreases to the level of 20/50 or worse. Some small stage 2 macular holes will close spontaneously, so it is reasonable to follow up a patient for a month with a small stage 2 macular hole, minimal symptoms, good visual acuity (20/30 or better), and vitreous traction to the flap at the edge of the macular hole. Spontaneous closure of the macular hole occurred spontaneously in 10.6% of eyes with injection of intravitreal saline in the ocriplasmin trial. 12 If the macular hole is monitored and increases in size with decreasing visual acuity, it is reasonable to consider vitrectomy. The visual needs of the patient and symptoms are important criteria that help to determine the recommended timing of macular hole surgery. The success rate for improving visual acuity following macular hole surgery is excellent, so almost all patients with symptomatic full-thickness macular holes should receive treatment. In about one-eighth of patients with unilateral macular holes, a macular hole eventually develops in the fellow eye. 6 , 7 , 19 Patients should be informed of this when they are presented with the treatment options for unilateral macular holes. Table 17-1 summarizes the general recommendations for surgery in eyes with different categories of macular holes.
Patients judge the success of macular hole surgery by the improvement in their vision, not by the anatomic status of the macular hole (open or closed).
Patients with bilateral macular holes of less than 2 years’ duration should be considered for macular hole surgery in both eyes. The success of macular hole surgery cannot be predicted for each eye, so bilateral surgery gives the patient the best chance for maximal visual recovery. Patients who have bilateral macular holes and one eye with a chronic macular hole more than 2 years old generally benefit from treatment of the more recent macular hole. If the outcome is good, then the expectations for surgery in the fellow eye with a chronic macular hole can be discussed so that the patient can make an informed decision about the fellow eye.
Macular hole surgery is never an emergent procedure, and patients should be informed of the treatment options and allowed to decide whether or not to proceed with macular hole surgery electively. Most macular hole surgery can be scheduled within several weeks of initial presentation to the vitreoretinal surgeon. Some patients wish to wait longer periods of time, but prolonged waits (3 or more months) may reduce the chances of visual and anatomic success because the preoperative visual acuity and potential postoperative visual acuity typically decrease as the hole becomes older and enlarges. Macular hole surgery can typically be performed under local/monitored anesthesia using small-gauge vitrectomy instrumentation on an outpatient basis.
Some patients are less favorable candidates for macular hole surgery, but improvements in techniques allow many of these patients to have successful closure of the macular hole with improved visual acuity. If a patient is unwilling or unable to remain prone postoperatively, prior cataract surgery and a large, long-acting gas bubble will allow adequate tamponade to close most macular holes. Patients who are unreliable in returning for office visits, have very limited visual needs, or are noncompliant with following postoperative instructions may not be good candidates for surgery.
17.4.3 Surgical Technique
The basic steps of the technique for macular hole surgery are summarized in the following list.
Basic Steps for Macular Hole Surgery
Three-port pars plana vitrectomy
Creation of posterior vitreous detachment in eyes with incomplete vitreous detachment
Removal of detached posterior hyaloid and trimming of the vitreous to peripheral vitreous base
Removal of ILM around the macular hole (with or without staining of ILM)
Check periphery for retinal tears and treat tears with laser/cryopexy
Prone positioning (if used)
A standard, three-port pars plana vitrectomy is performed with the goal of removing most of the vitreous (see ¦Chapter 40¦). It is essential to identify and remove the attached posterior hyaloid in eyes with macular holes because the posterior hyaloid contributes to traction in stages 2 and 3 macular holes. Although it is already separated, removal of the posterior vitreous is also desirable in eyes with stage 4 macular holes to create room for a large intraocular gas bubble. It is not necessary to perform simultaneous scleral indentation during vitrectomy for aggressive shaving of the vitreous base, as this maneuver may increase the risk of creating peripheral retinal tears.
Several techniques can be used to identify adherent posterior cortical vitreous and separate it from the retina. A commonly employed technique involves the use of a cannula with a soft silicone tip. With active aspiration, the soft-tip cannula is used to “search” for the posterior cortical vitreous. If the flexible silicone tip is slowly brushed about 0.5 mm anterior to the retina near the fovea or over the optic nerve head, it will seem to jump to any residual cortical vitreous when plugged by the gel, the so-called fish strike sign (Fig. 17-11). Once engaged, the gel is separated by gently pulling anteriorly. Because the cortical vitreous gel can be strongly adherent to the posterior pole, many surgeons opt to use larger, rigid cannulas or even the vitreous cutting/aspirating probe itself. The larger diameter openings of these instruments allow the vitreous gel to be grasped more firmly. If the vitreous is strongly adherent to the retina, which is especially common in traumatic macular holes in children/young adults, the infusion pressure can be increased and the aspiration suction increased to start the vitreous separation. Although fluidics has improved substantially with the newest generation of vitrectomy systems, care must be taken so that the eye does not collapse suddenly as aspiration suction is increased. The intravitreal instillation of triamcinolone in the course of the performing the vitrectomy is a popular way to help visual vitreous gel and insure complete removal from the posterior retina.
With all these separating techniques, the induced vitreous detachment is extended peripherally to about the equator by pulling the posterior hyaloid forward into the midvitreous cavity. The macular hole is observed as the posterior hyaloid is peeled from around the edges of the macular hole, to be certain that the hyaloid separates easily from the edges of the macular hole. The posterior hyaloid virtually always separates from the macular hole without visibly damaging the fovea. Occasionally, in an area of peripheral vitreoretinal adhesion such as lattice degeneration, a retinal tear will be created. The onset of mild vitreous bleeding as the posterior vitreous detachment is extended anteriorly strongly suggests a peripheral retinal break. The vitreous cutter is then used to remove the remaining posterior cortical vitreous and hyaloid to the posterior border of the vitreous base.
Almost all vitreoretinal surgeons routinely remove the ILM around the macular hole, as this has been shown in most studies to improve the success rate of closing the macular hole. A number of studies have confirmed that ILM peeling improves the chance of closing the macular hole with one surgery. 8 , 20 , 21 , 22 , 23 , 24 , 25 A meta-analysis of randomized clinical trials by the Cochrane Eyes and Vision Group found that ILM peeling was associated with improved anatomic success of closing macular holes and improved visual results at 3 months postoperatively. 26 There are three basic techniques to remove the ILM. The first is removal of the ILM with no staining. This can be difficult in some eyes, especially when the fundus is lightly pigmented. The ILM usually tends to fragment and it can be difficult to find the edge of the ILM. However, visual acuity results can be equivalent to eyes where indocyanine green (ICG) stain is used to peel the ILM. 27 , 28 , 29 , 30 , 31 , 32 Some studies have reported improved results with ICG staining compared to no staining of the ILM. 33 , 34 , 35 , 36 The second technique uses triamcinolone to delineate the surface of the retina (and ILM). The triamcinolone is dusted onto the surface of the macula. It does not stain the ILM but allows the surgeon to see where the ILM has been removed as removal of the ILM removes the triamcinolone particles on the surface of the retina. 37 The third technique is for surgeons to stain the ILM. The dye most commonly used to stain the ILM in the United States is ICG. This dye stains the ILM well but can cause retinal toxicity in some eyes, so the goal is to use a low concentration and only stain the ILM around the macular hole. A useful technique is to perform a fluid–air exchange just before instilling the ICG and place only one to three drops of ICG anterior to the macular hole. The ICG is then lavaged out of the eye when the air is removed. The second stain is brilliant blue G. This is not FDA approved in the United States but is commonly used in other parts of the world where it is approved by local authorities. It does not stain the ILM as well as ICG does but provides adequate staining in many eyes. The safety profile of brilliant blue G appears to be better than ICG. The third stain is trypan blue. Trypan blue does not stain the ILM very well, and it is often necessary to apply more trypan blue to restain the ILM if the staining is inadequate to see the ILM. Trypan blue appears to be relatively safe, 38 , 39 , 40 similar to brilliant blue G, but has largely fallen out of favor due to poor staining of the ILM. The literature is divided about whether ICG staining of the ILM is helpful or harmful. A number of studies have reported that visual acuity outcomes in eyes in which ICG was used are equivalent to visual acuity outcomes in eyes in which ICG was not used. 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 40 A few studies have found long-term ocular damage due to ICG, including RPE atrophy, visual field defects, and optic nerve atrophy. 41 , 42 , 43 , 44 The technique with which ICG is used to stain the ILM appears to be an important determining factor in whether or not ICG causes RPE toxicity.
Almost all vitreoretinal surgeons routinely remove the ILM around the macular hole, as this has been shown in most studies to improve the success rate of closing the macular hole.