Physicians try new techniques to manage macular hole, but cause still elusive

Despite advances and research regarding the natural history of the macular hole, questions remain concerning its cause and the preferred management strategy.

In the 2 decades since Neil E. Kelly, MD, and Robert T. Wendel, MD, first described surgical repair of macular holes, advances in surgical management have improved anatomical closure rates. But patients today, even after successful hole closure, may not have improvement in visual acuity, so there are still questions about the correlation between structural repair and functional restoration of the visual system.

Innovations in retinal imaging have offered greater insight into the pathogenesis of macular hole, but the exact etiology remains a mystery. Most likely, vitreous separation from the macula plays a role in the pathogenesis of macular holes.

Improvements in the surgical management of macular holes have resulted in better outcomes since 1991. Until then, no surgical option existed.

“The original thesis was to reattach the cuff of fluid that surrounds the hole and just make vision defects smaller. [Kelly and Wendel] were delighted to find that the holes went away,” Steve Charles, MD, said.

Steve Charles, MD, recommends peeling the ILM in every macular hole repair surgery to remove residual vitreous cortex and epiretinal membrane. Image: Culley G

Kelly and Wendel described restoration of the retinal anatomy in 73% of patients, with overall success of surgery – repair plus improvement in vision – in 42% of patients. Today, the success rate of surgery hovers around 90%, due in large part to refinements in the surgical technique, but also to improvements in the understanding of the role of the internal limiting membrane (ILM).

An evolving surgery

Studies have demonstrated the usefulness of ILM peeling in macular hole repair, although the exact reason for the benefit is not fully known. Dr. Charles said it is clear that peeling the ILM releases tangential traction.

“ILM peeling eliminates surface traction, but it can be demonstrated that ILM peeling improves retinal compliance as well,” Dr. Charles said. “It eliminates this rubber sheet on the retinal surface that is pulling it outwards from the pinhole on the macula, and it allows the retina to be more compliant.”

But there are still questions about how and when to remove the ILM. Dr. Charles said the ILM should be removed in every surgery because it removes residual vitreous cortex and epiretinal membrane, if present, in addition to increasing retinal compliance. Others point to the spontaneous resolution in some cases of macular holes smaller than 400 µm, as well as the ability to close such holes without ILM peeling, as evidence that the extra step may not always be necessary.

In a recent article in the American Journal of Ophthalmology, Alain Gaudric, MD, proposed that macular holes are not a homogenous group with respect to closure, with higher closure rates demonstrated in small holes and vice versa. Therefore, he concluded, a solution that might be explored is to tailor the surgical intervention to the individual needs of the patient. Smaller holes could be addressed with vitrectomy, fluid-gas exchange and postoperative positioning, whereas “holes larger than 400 µm probably require ILM peeling with the help of nontoxic dyes.”

Surgical management

Most retinal specialists say that ILM peeling is necessary in some, if not all, macular hole surgeries, but opinions differ on the proper role of staining. Several studies have suggested that the use of indocyanine green (ICG) is essential for visualization of the ILM but that its use may be associated with toxicity to the retina. Alternative staining mediums, such as trypan blue, have been studied, but they, too, have been associated with retinal toxicity.

“ICG, brilliant blue and trypan blue are useful tools for staining the ILM,” Dennis S.C. Lam, MD, FRCOphth, said, but “ICG toxicity has been reported and should be used with caution. Methods to minimize toxicity should be utilized.”

The use of staining is unnecessary if the correct surgical instruments are used, according to Dr. Charles. End-gripping Alcon DSP ILM forceps used in conjunction with a plano contact lens, which allows optimal viewing compared with wide-angle noncontact viewing systems that degrade lateral and axial resolution, should allow the surgeon to remove the shiny membrane without the use of toxic stains.

Another issue in the repair of macular holes is the need for face-down positioning in the recovery period after surgery. Some recent studies have suggested surgical protocols that require no specific positioning and use silicone oil in place of a gas bubble. However, that method requires a second surgical procedure to remove the oil and still may not be optimal for achieving hole closure. Dr. Charles noted that silicone oil produces 50% less surface tension than air or gas, significantly reducing closure rates.

The need for face-down positioning for at least a portion of the recovery period may be tied to how macular holes close. New evidence has emerged from research by Vincent Reppucci, MD, that lateral capillary forces at the site of the hole cause an immediate closure of the hole. Much like splinting a broken bone, in which appositional forces hold the fracture in place while osteoblasts repair the site, a gas bubble pulls the hole margins together via surface tension until astrocytes complete the repair.

“The hole closes immediately, the second the bubble’s been in contact,” Dr. Charles said. “It’s not slow glial healing, which is what everybody thought.”

The theories about macular hole repair bring up another point: whether partial or complete vitrectomy is preferred. The amount of vitreous removed during surgery may be dependent on the size of the gas bubble used to initiate the repair process, which, in turn, may depend on the size of the hole to be repaired.

The presence of the gas bubble, then, requires face-down positioning for repair, but also to reduce the risk of posterior subcapsular “gas” cataract development. If the patient were not in this position after surgery, the gas bubble may come in contact with the back of the lens, a risk factor for drying of the lens and the development of a cataract. The current standard is to require 1 to 3 weeks of face-down positioning after surgery, depending on whether SF6 or C3F8 gas is used.

“Current data suggest that macular holes close very early during the postop period. Therefore, shortening the duration of face-down posturing seems to be logical,” Prof. Lam said. “Better understanding of the physics and mechanics of macular hole closure suggests that posturing might not be necessary provided that the initial gas bubble is large enough.”

One option to reduce the risk of cataract development in phakic eyes is to perform phacovitrectomy, but the presence of the macular hole may skew axial length readings during biometry. The combined procedure is common in some areas of the world, and surgeons have not seen any indications of diminished results.

“Phacovitrectomy has been routine at our center for many years for suitable cases, and we have found the procedure to be safe and effective,” Prof. Lam said. “Any intraocular lens can be used in patients undergoing phacovitrectomy for macular hole repair.”

See better, treat better

Optical coherence tomography has been an important innovation for macular holes, especially during the diagnostic phase. Previously, retinal surgeons were confined to fluorescein angiography, ophthalmoscopic examination and psychophysical assessment, such as the line resolution test (Watzke-Allen test).

While some contend that staging of macular holes, even in the widely used system developed by J. Donald M. Gass, MD, is inexact, it can provide a framework from which to predict the potential for spontaneous resolution or poor prognosis.

OCT is essential for differentiating between partial- and full-thickness holes, Dr. Charles said, but it cannot tell which partial-thickness holes will become full-thickness. He said that symptomatic partial-thickness holes should be repaired with ILM without staining and SF6 gas.

Michael S. Ip

“If the patient has a stage 1 macular hole, in other words not a full-thickness macular hole, you can tell the patient, we do not need to operate on you yet, you have a 50% chance that this will spontaneously resolve or will not require surgery,” Michael S. Ip, MD, said.

Suggestive findings on OCT, then, may mean the difference between exposing the patient to the potential complications of retinal surgery and the difficulties of the healing period, or delaying surgery to see if the hole goes away on its own.

“It’s not a trivial operation in terms of potential side effects, and it’s not a trivial operation for the patient, and so this distinction is critically important,” Dr. Ip said. “OCT is extremely helpful in this type of diagnostic dilemma when you are confronted with a patient with vision loss from a pre-macular hole or a very early full-thickness macular hole.”

Compared with time-domain OCT, spectral-domain OCT offers greater resolution in imaging, as well as a consistent interscan reference point, which is important for a patient with a stage 1 macular hole being followed for potential spontaneous regression.

“Distinguishing early stage macular holes from garden variety epiretinal membrane or vitreoretinal traction syndrome is helpful when using spectral-domain OCT over time-domain OCT,” Dr. Ip said.

The use of OCT may be equally important in the postoperative period. The greater resolution offered by spectral-domain technology can reveal whether surgery was successful in completing the structural repair.

Visual symptoms may not always resolve after macular hole surgery. Some patients may not experience improvement in visual acuity even after successful anatomical repair, while others will continue to have visual impairment because the hole was not successfully closed. In addition, Dr. Charles said he thinks that ICG staining is a major cause of poor vision after successful hole closure.

“If the vision is down and that is because the macular hole did not close, well then that is a whole different story. You may want to take the patient back for repeat surgery,” Dr. Ip said.

OCT in macular hole research

Another way OCT has changed the understanding of macular holes is in research applications. In a 2006 study published in Archives of Ophthalmology, researchers used a ultrahigh-resolution OCT device capable of achieving approximately 3-µm axial resolution to identify persistent retinal abnormalities despite anatomical macular hole closure in 22 patients.

In the study, preoperative visual acuity ranged from 20/25 to 2/200, with a mean of 20/158. Despite confirmation of hole closure on standard-resolution OCT, postoperative visual acuity ranged from 20/25 to 4/200, with a mean of 20/110. In addition, eight patients had a best corrected visual acuity worse than 20/200 at the first postoperative visit.

Ultrahigh-resolution OCT, however, showed the presence of five different retinal abnormalities in the patient population: outer foveal hyporeflective defect, persistent foveal detachment, moderately reflective foveal lesion, epiretinal membrane and nerve fiber layer defect.

“Foveal photoreceptor abnormalities were consistent findings in all patients,” the study authors said. “Foveal photoreceptor defects suggest residual abnormalities in photoreceptor cells after macular hole.”

Epiretinal membranes were a common feature on ultrahigh-resolution OCT, occurring in 14 of 22 patients. However, the finding is not unexpected, the study noted, because the surgical repair of macular holes requires the creation of a posterior vitreous detachment, a known risk factor for epiretinal membrane formation.

According to the study, the moderately reflective foveal lesions may represent “glial cell proliferative response that replaces normal foveal anatomy at the region of retinal reapproximation after macular hole surgery.” The implications of this finding, however, are unknown. Another finding, nerve fiber layer defects, identified in three patients, may have resulted from ILM peeling performed in some patients.

The defects were recognized using a prototype OCT device, but newer high-resolution OCT devices may be able to detect these fine retinal defects after successful hole closure.

Jay S. Duker

“I would think that resolution of the Stratus OCT (Carl Zeiss Meditec), which is a time-domain OCT, is such that retinal thinning can be detected, but the layer of the retina that is abnormal would be difficult to tell,” Jay S. Duker, MD, a co-author of the study, said. “Some of the new devices, the spectral-domain OCT, have resolution in the 4-µm to 7-µm range, and that is usually sufficient to see that the defects are in the outer retina.”

Other OCT applications

In a separate study using OCT imaging, Dr. Duker and colleagues offered suggestive evidence that OCT findings in patients with unilateral macular holes may identify risk factors for the future development of macular holes in fellow eyes. Patients with abnormalities of the vitreoretinal interface in the fellow eye were at greater risk for developing a macular hole in that eye.

In the study, fellow eyes were classified as having a stage 0 macular hole if an abnormally inserting posterior hyaloid was present at the fovea. Of four patients with severe abnormalities of the vitreoretinal interface, one developed a macular hole. Of eight patients with a moderate abnormality, four developed a macular hole. However, of the 15 patients with mildly visible, abnormally inserting posterior hyaloid, none developed a macular hole. And in 67 patients with no evidence of a stage 0 macular hole, only three patients later developed a macular hole.

“A stage 0 macular hole is defined as a clinically normal eye with a normal foveal contour and normal retinal thickness on OCT, but must also have a preretinal, minimally reflective, thin band (posterior hyaloid) inserting on at least one side of the fovea as a result of oblique traction,” according to the study.

Overall, the low incidence of hole development in fellow eyes in patients with no signs of abnormalities of the vitreoretinal interface (4.5%) coupled with the high incidence in patients with positive evidence of abnormalities (42%) suggest an increased risk. In addition, univariate analysis revealed an almost sixfold increased risk in macular hole formation in fellow eyes with a stage 0 hole.

“What the paper showed is that in a patient with a macular hole in one eye, by looking at the OCT in the fellow eye, you can predict the risk of future macular hole in the fellow eye,” Dr. Duker said.

These findings were identified with a time-domain OCT device, but newer spectral-domain OCT devices would also likely show these changes, he said.

Another area of research pertaining to OCT with respect to macular holes is whether imaging can be used to guide the duration of face-down positioning after surgery. According to some published studies, Dr. Duker said, if the hole is deemed to be closed on postoperative day 1 on OCT, it may be possible to limit or eliminate future positional requirements during the recovery period; while his laboratory is investigating that potential, it is still too early to suggest any changes to the current protocol.

“I think it’s premature to speculate on that,” Dr. Duker said. “I would say that this is a future area of research and a possible future use of OCT in macular holes to tailor face-down positioning, but we do not have enough data to do that yet.” – by Bryan Bechtel

Is there a role for silicone oil in the repair of macular hole?

References:

• Chan A, Duker JS, Schuman JS, Fujimoto JG. Stage 0 macular holes: Observations by optical coherence tomography. Ophthalmology. 2004;111(11):2027-2032.
• Gaudric A. Macula hole surgery: Simple or complex? Am J Ophthalmol. 2009;147(3):381-383.
• 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(1):29-35.
• Kelly NE, Wendel RT. Vitreous surgery for idiopathic macular holes. Results of a pilot study. Arch Ophthalmol. 1991;109(5):654-659.
• Ko TH, Fujimoto JG, Duker JS, et al. Comparison of ultrahigh- and standard-resolution optical coherence tomography for imaging macular hole pathology and repair. Ophthalmology. 2004;111(11):2033-2043.
• Ko TH, Fujimoto JG, Schuman JS, et al. Comparison of ultrahigh- and standard-resolution optical coherence tomography for imaging macular pathology. Ophthalmology. 2005;112(11):1922.
• Ko TH, Witkin AJ, Fujimoto JG, et al. Ultrahigh-resolution optical coherence tomography of surgically closed macular holes. Arch Ophthalmol. 2006;124(6):827-836.
• Wendel RT, Patel AC, Kelly NE, et al. Vitreous surgery for macular holes. Ophthalmology. 1993;100(11):1671-1676.
• Witkin AJ, Ko TH, Fujimoto JG, et al. Redefining lamellar holes and the vitreomacular interface: An ultrahigh-resolution optical coherence tomography study. Ophthalmology. 2006;113(3):388-397.

• Steve Charles, MD, can be reached at Charles Retina Institute, 6401 Poplar Ave., Suite 190, Memphis, TN 38119; 901-767-4499; fax: 901-761-0727; e-mail: scharles@att.net.
• Jay S. Duker, MD, can be reached at New England Eye Center, 800 Washington St., Box 450, Boston, MA 02111-1533; 617-636-4604; fax: 617-636-4866; e-mail: jduker@tuftsmedicalcenter.org.
• Michael S. Ip, MD, can be reached at University of Wisconsin, Fundus Photograph Reading Center, Park West One, 406 Science Drive, Suite 400, Madison, WI 53711-1068; 608-263-2853; fax: 608-262-1899; e-mail: msip@wisc.edu.
• Dennis S.C. Lam, MD, FRCOphth, can be reached at Hong Kong Eye Hospital, The Chinese University of Hong Kong, 3/F, 147K Argyle Street, Kowloon, Hong Kong SAR, China; 852-2762-3157; fax: 852-2715-9490; e-mail: dennislam_pub@cuhk.edu.hk.