Chapter 128 – Macular Hole
JAY S. DUKER
• A full-thickness depletion of the neural retinal tissue in the center of the macula.
• Central scotoma.
• Round, central neural retinal tissue defect.
• Cystic retinal changes in the perifoveolar area that surrounds the macular hole.
• Yellow spots in the base of the macular hole.
• Small surrounding cuff of subretinal fluid.
• Attached posterior hyaloid initially.
• Epiretinal membrane.
• Occasionally bilateral (10–20%).
• Retinal detachment (rare), previous trauma (rare), previous macular edema (rare).
Idiopathic macular holes were identified as a unique clinical entity more than 100 years ago,  and Ogilvie is credited with introducing the term macular hole. Until recently, ophthalmologists paid little attention to macular holes, because the pathogenesis was obscure and cure impossible. Recently, interest in this entity has increased dramatically. Although the pathogenesis remains incompletely understood, a new classification has emerged that accounts for premacular hole clinical appearances and gives insight into the intraocular processes that lead to macular hole formation.    In addition, some new ancillary tests are now available to assist in the diagnosis.    Most importantly, there is now surgical therapy to reverse the visual loss in most cases. 
EPIDEMIOLOGY AND PATHOGENESIS
The majority of macular holes are idiopathic, occurring in eyes that have no previous ocular pathology. Exceptionally, a pathological process can induce secondarily the formation of a macular hole. A macular hole can form immediately after blunt trauma—the initial published description of a macular hole by Herman Knapp in 1869 was of one in a previously traumatized eye. Besides trauma, other ocular problems have been associated with macular hole formation including cystoid macular edema, epiretinal membrane, vitreomacular traction syndrome, rhegmatogenous retinal detachment, inadvertent exposure to laser energy, Best’s disease, high myopia with posterior staphyloma, lightning strike injury, hypertensive retinopathy, and proliferative diabetic retinopathy.   
Idiopathic macular hole most commonly affects otherwise healthy individuals in their sixth or seventh decade of life. The mean age of onset is 65 years, but onset in patients as young as the third decade has been reported. Women are affected more commonly than men by a 2:1 ratio, an observation made many years ago but confirmed only recently by a well-designed case-control study. About 10–20% of individuals eventually are affected bilaterally, but onset is rarely simultaneous.  
For years, investigators sought systemic reasons why idiopathic macular holes should form. Previous studies implicated cardiovascular disease, hypertension, and previous hysterectomy as possible risk factors; however, no confirming evidence supports these associations. In the Eye Disease Case-Control study, many possible systemic risk factors were examined prospectively. Only elevated serum fibrinogen levels correlated with an increased risk of idiopathic macular hole. Macular holes are rare conditions, estimated to occur in the vicinity of 1 in 5000 patients.
Although the precise pathogenesis of idiopathic macular hole remains speculative, evidence suggests that abnormal tractional forces of the vitreous on the macula are directly responsible. Such tractional forces can be observed clinically with contact lens examination, with ultrasonography, and with newer imaging techniques like optical coherence tomography and laser biomicroscopy.     The success of vitreous surgery for macular holes provides strong evidence for a direct role of the vitreous in pathogenesis.
The hallmark complaint of idiopathic macular hole formation is painless central visual distortion or blur of an acute or subacute nature. Quite typically, when only one eye is involved, the visual loss goes undetected unless cross-covering is performed. Central visual acuity initially may be diminished only mildly; however, as the hole progresses over weeks to months, the acuity usually deteriorates, then stabilizes around the 20/200–20/800 (6/60–6/240) level.
A currently accepted system of stages based on biomicroscopic observations was reported initially by Gass in 1988 and then revised in 1995; it explains the clinically observed appearances of macular holes and their precursor lesions. The hallmark inciting event of idiopathic macular hole formation is hypothesized to be focal shrinkage of the vitreous cortex in the foveal area.    Clinically, four stages occur in idiopathic macular hole development. Although Gass’ biomicroscopic interpretations of the various stages are accepted widely, newer imaging techniques imply that the pathological processes that occur in stage 1 holes may differ slightly from the accepted classification.   
In idiopathic macular hole, impaired visual function is probably multifactorial. Photoreceptor loss from the central foveal area may occur in some cases, although a true retinal operculum rarely is evident. The central scotoma that results from foveal dehiscence is made significantly larger by the surrounding localized
retinal detachment. Cystic changes develop in the intact perifoveal retina, as well, and some eyes develop epiretinal membranes. All the factors combine to decrease the central vision. Rhegmatogenous retinal detachment beyond the macula occurs secondary to a macular hole only if abnormal vitreous traction or extreme myopia with staphyloma is present concurrently.
Stage 1 Macular Hole
With a unilateral stage 1 macular hole, the patient typically is asymptomatic with both eyes open. For this reason and because they are evanescent lesions, stage 1 macular holes are not observed commonly and their diagnosis can be difficult. When symptoms are present, they consist of painless metamorphopsia or decreased vision or both. Stage 1 macular holes also have been referred to as premacular holes, macular cysts, or involutional macular thinning.
In a stage 1 macular hole, no true neural retinal defect is present, the photoreceptor layer is believed to be intact, and no vitreofoveal separation has occurred. Tangential or oblique vitreous traction on the fovea is hypothesized to be the inciting event. Stage 1 holes are further divided into stage 1a and stage 1b, based on clinical appearance. In a stage 1a macular hole, a small central yellow spot is seen on ophthalmoscopy. The fovea may be thickened along with a loss of the normal foveal contour. In a stage 1b macular hole, a yellow ring is visible in the foveal area.   
Gass suggests that the yellow spot of a stage 1a macular hole results from a small foveal detachment. Other observers, bolstered by ancillary testing, conclude that a stage 1a macular hole actually represents a cystic change in the fovea, rather than a true photoreceptor detachment from the retinal pigment epithelium.    In a stage 1b macular hole, the cyst-like space or foveal detachment enlarges to a point just short of actual dehiscence.
Stage 1 holes spontaneously resolve in about 50% of eyes with no visual sequelae ( Fig. 128-1 ). The worse the initial visual acuity, the less likely is spontaneous resolution.
Stage 2 Macular Hole
When continued shrinkage of the perifoveal vitreous cortex occurs, a stage 1 hole advances to a stage 2 hole. Stage 2 holes have a small (100–200?µm), full-thickness neural retinal defect, either centrally or eccentrically. The defect can be round, oval, crescentic, or horseshoe shaped ( Fig. 128-2 ). The visual acuity typically is diminished and a pseudo-operculum, which represents condensed vitreous, may overlie the hole. It is believed that once a stage 2 hole occurs, it nearly always progresses to stage 3, with little hope for spontaneous visual improvement. The visual acuity with a stage 2 hole varies between 20/50 (6/15) and 20/400 (6/120).
Stage 3 Macular Hole
Stage 3 macular hole is the end result of continued vitreofoveal traction on a stage 2 hole. At stage 3, the hole is developed fully and has the classic appearance of an idiopathic macular hole. This consists of a round, 350–600?µm full-thickness neural retinal defect with smooth edges, and a small, surrounding, doughnut-shaped rim of subretinal fluid (see Fig. 128-1, A ). This fluid rarely progresses to cause a widespread retinal detachment. Yellow deposits can be seen in the base of the defect, and perifoveal cystic retinal changes are present. With time, retinal pigment epithelial alterations (pigmented demarcation line) may develop at the leading edge of the subretinal fluid cuff. The visual acuity typically is 20/200–20/800 (6/60–6/240); however, visual acuity as good as 20/40 (6/12) may be seen with a stage 3 hole, but rarely. Vitreofoveal separation still has not occurred.
Stage 4 Macular Hole
A stage 4 macular hole has all the features of a stage 3 hole, but with complete posterior separation of the vitreous from the fovea.
Figure 128-1 Spontaneous resolution of a macular hole. A, Full-thickness stage 3 macular hole in the right eye of a 62-year-old woman who has a visual acuity of 20/200 (6/60). B, Stage 1a macular hole of several weeks’ duration in the left eye of the same patient as shown in A. Visual acuity was 20/70 (6/21). Note central yellow spot. C, Several weeks later, spontaneous vitreofoveal separation has occurred in the eye shown in B, the stage 1a hole has resolved, and visual acuity is 20/30 (6/9).
Lamellar Macular Hole
A lamellar macular hole represents an aborted macular hole. Clinically, a round central inner retinal defect is found, with no thickening, cystic change, or subretinal fluid. An overlying operculum is common. Vitreofoveal separation occurs with loss of
Figure 128-2 Stage 2 macular hole. A, Eccentric stage 2 macular hole with a vision of 20/80 (6/24). B, Optical coherence tomography of same eye as in A, showing full-thickness defect with eccentric opening of inner retina, consistent with a stage 2 macular hole.
the inner retinal layers; however, the outer, photoreceptor layer is intact. The vision usually is good (20/20–20/30 [6/6–6/9]) and many patients are asymptomatic. Fluorescein angiography typically shows no abnormal fluorescence. It is believed that, because vitreofoveal separation has occurred, the risk of continued progression to a macular hole is insubstantial.
DIAGNOSIS AND ANCILLARY TESTING
The diagnosis of idiopathic macular hole is a clinical one, made at the slit lamp with a handheld or fixed lens, used in either a contact or noncontact fashion. At times, the diagnosis can be difficult, especially when a unilateral stage 1 or stage 2 hole is present. 
Ancillary testing can be helpful in certain cases. Fluorescein angiography is not diagnostic, although it can help to rule out other entities that mimic macular hole. In stage 1 macular holes, fluorescein angiography commonly is normal or reveals only a small window defect. Some stage 2 macular holes show an intense, small, central window defect, while others manifest normal angiography or a mild window defect. In a stage 3 or 4 macular hole, the window defect tends to be mild and corresponds in size and location to the retinal defect.
The slit-beam test (Watzke–Allen sign) usually is reliable to test subjectively for a full-thickness retinal defect. In this test, a thin, vertically oriented slit beam is focused on the macula and the patient is asked to describe the line of light. In a full-thickness defect, a break or thinning of the beam is seen centrally. The
Differential Diagnosis of Macular Hole
Cystoid macular edema
Vitreomacular traction syndrome
Choroidal neovascular membrane
Central areolar pigment epitheliopathy
Central serous chorioretinopathy
Lamellar (aborted) macular hole
scotoma associated with a macular hole can be mapped using the scanning laser ophthalmoscope or with the aiming beam of a laser.
Imaging tests of the retina and vitreous, such as ultrasonography, optical coherence tomography, and scanning laser biomicroscopy, are used to confirm the diagnosis and to assess the attachment of the vitreous to the fovea.    Optical coherence tomography appears to be the most clinically useful ancillary test.
Macular holes are most apt to be confused with epiretinal membranes, cystoid macular edema, or the vitreomacular traction syndrome. For the differential diagnosis of macular hole, an isolated ocular condition, see Box 128-1 .
Histopathological examination shows a round, full-thickness defect through all neural retinal layers. The underlying retinal pigment epithelium is intact. Associated intraretinal edema and perifoveal photoreceptor atrophy are common. Epiretinal membrane formation is also common.
In the few reported eyes that have undergone histopathological evaluation after successful vitreous surgery to close macular holes, fibroglial proliferation across the retinal defect has been observed.
Prior to 1989, idiopathic macular holes were considered untreatable. Kelly and Wendel were the first to report that vitreous surgery can improve the visual acuity in some eyes with acute, idiopathic macular holes. Since then, vitrectomy for idiopathic macular holes rapidly has become a widely performed procedure throughout the world.
Most surgeons do not advocate operating on stage 1 holes for three reasons:
• Stage 1 macular holes have a 50% rate of spontaneous improvement.
• Surgical intervention does not prevent macular hole formation universally, and intraoperative macular hole can occur.
• Vitrectomy for a stage 2 hole of recent onset has a very high (>90%) success rate.
Macular hole surgery typically is performed under local anesthesia, unless general anesthesia is requested by the patient. A standard three-port core vitrectomy is completed. Following this, the intact posterior cortical vitreous is engaged gently, using a silicone-tipped extrusion needle attached to the suction line of the vitrectomy instrument. Alternatively, the vitreous cutting instrument, a bent needle, or a pick can be used to engage the cortical vitreous. The posterior cortical vitreous is usually invisible until it is elevated off the retina. At that point, it appears as a diaphanous membrane that may insert on the edges of the macular
hole, the optic disc, or the midperipheral retina. Gentle elevation of the cortical vitreous and posterior hyaloid is carried out until complete separation of the vitreous is achieved. The remainder of the posterior vitreous is removed with the vitrectomy cutting instrument. At this juncture, epiretinal membrane, if present, is peeled using a bent, sharp needle or fine (ILM) forceps. If internal limiting membrane peeling is felt to be beneficial, it is performed at this stage. The internal limiting membrane can be stained with indocyanine green dye to make its surgical removal technically simpler. An air–fluid exchange follows, and if an adjunctive agent (e.g., transforming growth factor ß or autologous serum) is to be used, it is applied at this point. Air, dilute sulfur hexafluoride (SF6 ) gas, or dilute perfluoropropane (C3 F8 ) gas is placed in the vitreous cavity, and the sclerostomy sites are closed. The surgery can be performed safely in an outpatient setting. Patients usually are instructed to maintain strict face-down positioning for at least 7 days postoperatively.
As in any invasive surgical procedure, intraoperative and postoperative complications can occur ; some are unique to macular hole surgery, while others may develop during any vitreoretinal procedure. The most common complication after the surgery is cataract formation. It has long been known that vitrectomy in a phakic eye leads to accelerated nuclear sclerosis; the addition of intravitreal gas probably speeds the process. Over 50% of phakic eyes that undergo vitrectomy for a macular hole suffer significant nuclear sclerosis during the subsequent 2-year follow-up. In successful cases, eventual removal of the cataract by standard techniques can be performed without undue risk. Some surgeons advocate removal of clear lenses or minimal cataracts at the time of macular hole surgery to eliminate the need for a second procedure.
Retinal tears or retinal detachment or both may be seen in up to 10% of eyes that undergo vitreous surgery for an idiopathic macular hole. This incidence is relatively high, because an intraoperative and, therefore, traumatic creation of a posterior vitreous detachment is a critical step in the procedure. Intraoperative recognition of retinal tears with prompt treatment using either laser or cryotherapy can keep the occurrence of retinal detachment low. Some retinal tears develop during the immediate postoperative period, so vigilant postoperative fundus observation is necessary. Most retinal detachments can be repaired with standard scleral buckling, vitrectomy, or pneumatic retinopexy techniques.
Other, less common complications include intraoperative light or mechanical toxicity to the macular retinal pigment epithelium, intraoperative enlargement of the macular hole, and late reopening of successfully closed holes.    Late reopening occurs in 5% of once-successfully treated holes and can occur years after the initial surgery. Second operations to close the reopened holes may be successful in some cases. Some investigators have observed dense, temporal visual field defects in eyes that have undergone vitrectomy for macular holes. The cause and incidence is still unclear.
COURSE AND OUTCOME
Premacular holes (stage 1 holes) have a spontaneous rate of improvement of about 50%. A lamellar macular hole represents an abortive macular hole and is stable with good vision. Once a stage 2 hole occurs, without surgery visual loss is nearly always permanent. Spontaneous closure of full-thickness macular holes occurs in 2–4% of eyes, probably secondary to epiretinal membrane formation.   Visual improvement does not always occur concurrently.
Without surgery, macular holes tend to stabilize with a visual acuity of 20/200–20/800 (6/60–6/240) and a diameter of about 500?µm. With surgery, visual improvement is possible. Anatomical success can be determined 2–4 weeks after surgery, when the gas bubble has resorbed enough to be no longer in contact with the macular hole in the upright position.
Figure 128-3 Stage 2 macular hole. A, The same eye as in Figure 128-2 , 2 weeks after surgery. The hole is closed and the vision is 20/20 (6/6). The gas bubble is still visible superiorly. B, Optical coherence tomography postoperatively of same eye as in Figures 128-2 and A showing normal foveal architecture after surgery.
Anatomical success usually is defined as complete disappearance of the cuff of subretinal fluid that surrounds the macular hole. In most instances, when this occurs the edges of the macular hole are opposed firmly to the retinal pigment epithelium, which renders identification of the macular hole difficult ( Fig. 128-3 ). Visual success is defined as an improvement in postoperative visual acuity of at least two or more Snellen lines over preoperative acuity.
In their initial series of 52 treated eyes, Kelly and Wendel found that 42% showed a visual acuity improvement of two or more Snellen lines following surgery. A higher percentage, 58% of eyes, were considered anatomical successes. Their subsequent series showed that anatomical success could be achieved in 73% of eyes, with an improvement of two or more Snellen lines in 55%.  Best results were obtained when surgery was performed within 6 months of visual loss. A randomized, multicenter trial achieved a closure rate of 69%.
The results of two recent series of vitrectomy on early, small, stage 2 macular holes suggest a success rate of 90% or greater for anatomical closure, with visual improvement in 80% (see Fig. 128-3 ). 
1. Aaberg TM. Macular holes: a review. Surv Ophthalmol. 1970;15:139–62.
2. Knapp H. Ueber isolirte zerreissungen der aderhaut in folge von traumen auf dem augapfel. Arch Augenheilkd. 1869;1:6–29.
3. Ogilvie FM. On one of the results of concussive injuries of the eye (“holes” at the macula). Trans Ophthalmol Soc U K. 1900;20:202–29.
4. Gass JDM. Idiopathic senile macular hole: its early stages and pathogenesis. Arch Ophthalmol. 1988;106:629–39.
5. Johnson RN, Gass JDM. Idiopathic macular holes: observations, stages of formation, and implications for surgical intervention. Ophthalmology. 1988;95: 917–24.
6. Gass JDM. Reappraisal of biomicroscopic classification of stage of development of a macular hole. Arch Ophthalmol. 1995;119:752–9.
7. Kiryu J, Shahidi M, Ogura Y, et al. Illustration of the stages of idiopathic macular holes by laser biomicroscopy. Arch Ophthalmol. 1995;113:1156–60.
8. Kokame GT. Clinical correlation of ultrasonographic findings in macular holes. Am J Ophthalmol. 1995;119:441–51.
9. Hee MR, Puliafito CA, Wong C, et al. Optical coherence tomography of macular holes. Ophthalmology. 1995;102:748–56.
10. Kelly NE, Wendel RT. Vitreous surgery for idiopathic macular holes. Arch Ophthalmol. 1991;109:654–9.
11. Wendel RT, Patel AC, Kelly NE, et al. Vitreous surgery for macular holes. Ophthalmology. 1993;100:1671–6.
12. Brown GC. Macular hole following rhegmatogenous retinal detachment repair. Arch Ophthalmol. 1988;106:765–6.
13. Cohen SM, Gass JDM. Macular hole following severe hypertensive retinopathy. Arch Ophthalmol. 1994;112:878–9.
14. Flynn HW. Macular hole surgery in patients with proliferative diabetic retinopathy. Arch Ophthalmol. 1994;112:877–8.
15. The Eye Disease Case-Control Study Group. Risk factors for idiopathic macular hole. Am J Ophthalmol. 1994;118:754–61.
16. Bronstein MA, Trempe CL, Freeman HM. Fellow eyes of eyes with macular holes. Am J Ophthalmol. 1981;92:757–61.
17. Lewis ML, Cohen SM, Smiddy WE, Gass JDM. Bilaterality of idiopathic macular holes. Graefes Arch Klin Exp Ophthalmol. 1996;234:241–5.
18. Fisher YL, Slakter JS, Yannuzzi LA, Guyer DR. A prospective natural history study and kinetic ultrasound evaluation of idiopathic macular holes. Ophthalmology. 1994;101:5–11.
19. Martinez J, Smiddy WE, Kim J, Gass JDM. Differentiating macular holes from macular pseudoholes. Am J Ophthalmol. 1994;117:762–7.
20. Gass JDM, Joondeph BC. Observations concerning patients with suspected impending macular holes. Am J Ophthalmol. 1990;109:638–46.
21. Rosa RH, Glaser BM, de la Cruz Z, Green WR. Clinicopathologic correlation of an untreated macular hole and a macular hole treated by vitrectomy, transforming growth factor-2 and gas tamponade. Am J Ophthalmol. 1996;122:853–63.
22. Park S, Marcus DM, Duker JS, et al. Posterior segment complications after vitrectomy for macular hole. Ophthalmology. 1995;102:775–81.
23. Poliner LS, Tornambe PE. Retinal pigment epitheliopathy after macular hole surgery. Ophthalmology. 1992;99:1671–7.
24. Duker JS, Wendel R, Patel A, Puliafito CA. Late reopening of macular holes following initially successful vitreous surgery. Ophthalmology. 1994;101:1373–8.
25. Boldt HC, Munden PM, Folk JC, Mehaffey MG. Visual field defects after macular hole surgery. Am J Ophthalmol. 1996;122:371–81.
26. Freeman WR, Azen AP, Kim JW, et al. Vitrectomy for the treatment of full-thickness stage 3 or 4 macular holes. Arch Ophthalmol. 1997;115:11–21.
27. Lewis H, Cowan GM, Straatsma BR. Apparent disappearance of a macular hole associated with development of an epiretinal membrane. Am J Ophthalmol. 1986;102:172–5.
28. Ryan EH, Gilbert HD. Results of surgical treatment of recent-onset full-thickness idiopathic macular holes. Arch Ophthalmol. 1994;112:1545–53.
29. Ip MS, Baker BJ, Duker JS, et al. Anatomical outcomes of surgery for idiopathic macular hole as determined by optical coherence tomography. Arch Ophthalmol. 2002;120:29–35.