Macular Hole Treatment & Management

Case reports exist that describe the use of autologous plasmin for idiopathic and traumatic macular holes. Ongoing clinical trials are evaluating the role of plasmin as a means of “chemovitrectomy.” In these studies, case illustrations have demonstrated resolution of idiopathic macular holes following intravitreal injection of plasmin and no surgical intervention.

In October 2012, ocriplasmin (Jetrea) was approved by the US Food and Drug Administration (FDA) for the treatment of vitreomacular adhesion. Ocriplasmin is a recombinant proteolytic enzyme that underwent study by the MIVI-TRUST study group. This protease demonstrated activity against fibronectin and laminin. In a randomized, double-blind study, 652 eyes with vitreomacular adhesion were treated with an intravitreal injection of ocriplasmin. A secondary endpoint of the study was nonsurgical closure of a full-thickness macular hole (FTMH), which can result from vitreomacular adhesion. In the study, 40.6% of treated eyes experienced nonsurgical closure of the macular hole compared to 10.6% in the placebo group (P< 0.001). FDA approval was based on this study. This injectable medication provides a nonsurgical means of treating macular holes. ^[7]

A 2018 study suggests slightly higher closure rates for full-thickness macular hole following ocriplasmin use. They described 6 patients with vitreomacular traction and a full-thickness macular hole. By 24 weeks’ of follow-up, four of the six full-thickness macular holes had closed. ^[8] Other studies have confirmed a relatively low rate of macular hole closure even with release of vitreomacular traction despite careful selection of treatment candidates. ^{[9, 10, 11]} One retrospective study suggests that only approximately 18% of patients with macular hole could be favorable candidates for ocriplasmin treatment. ^[9]

There are concerns with the potential for retinal toxicity from the use of ocriplasmin (See Medication below).

The potential for better vision, as well as the 12% chance that the fellow eye will develop another macular hole, has prompted ophthalmologists to seek for a viable treatment of this condition.

Indications for consideration of the surgical management of macular holes are based on the presence of a full-thickness defect. Once this defect has developed, the potential for spontaneous resolution is low. Thus, surgical management is recommended with documentation of a stage 2 or higher, full-thickness macular hole. Stage 1 holes and lamellar holes are managed conservatively with observation at this time. See Controversies surrounding the surgical repair of macular holes.

Historically, therapy for macular holes has evolved from pharmacologic interventions, such as anxiolytics and vasodilators, to an assortment of surgical techniques, such as cerclage, scleral buckles, direct photocoagulation of the hole edges, and intraocular gas tamponade without the aid of vitrectomy. In 1982, Gonvers and Machemer were the first to recommend vitrectomy, intravitreal gas, and prone positioning for retinal detachments secondary to macular holes. ^[12]

Kelly and Wendel reported that vision might be stabilized or even improved if it were possible to surgically relieve tangential traction on the macula, reduce the cystic changes, and reattach the cuff of detached retina surrounding the macular hole. ^[13] They proposed that by performing this surgery, they could flatten the retina and possibly reduce the adjacent cystic retinal changes and neurosensory macular detachment. ^[13]

In 1991, Kelly and Wendel demonstrated that vitrectomy, removal of cortical vitreous and epiretinal membranes, and strict face-down gas tamponade could successfully treat full-thickness macular holes. ^[13] The overall results of their initial report were a 58% anatomic success rate and visual improvement of 2 or more lines in 42% of eyes. A succeeding report showed a 73% anatomic success rate and 55% of patients improving 2 or more lines of visual acuity. Present anatomic success rates range from 82-100% depending on the series.

A prospective, randomized, and controlled series by the Vitrectomy for Treatment of Macular Hole Study Group for stage 2, 3, and 4 holes showed that vision was improved in surgically treated eyes compared with observed eyes. However, more frequent adverse effects were observed in the surgically treated eyes compared to the control eyes, with the most common adverse effects being macular retinal pigment epithelium changes and cataractogenesis.

Some aspects of the surgery may vary, but the basic technique is the same. The anterior and middle vitreous is removed via a standard 3-port pars plana vitrectomy. Patients with macular hole frequently undergo vitrectomy using smaller gauge vitrectomy systems (ie, 27 gauge, 25 gauge, 23 gauge). Associated instruments have been developed for these smaller gauge, transconjunctival vitrectomy systems.

The critical step appears to be the removal of the perimacular traction. Factors contributing to this traction, such as the posterior hyaloid, the ILM, and coexisting epimacular membranes, need to be addressed. The traction exerted by the posterior hyaloid on the macula should be relieved by either removing just the perimacular vitreous or combining it with the induction of a complete posterior vitreous detachment. Various surgical techniques have been described to accomplish this task, including the use of a soft-tipped silicon cannula or the vitrectomy cutter with the cutter disengaged. A "fish-strike sign" or bending of the silicon cannula has been described as a sign that the posterior hyaloid has been engaged. Then, it may be released from the underlying retina and removed with the vitrectomy cutter.

The removal of ILM is considered to be a contributing factor in the success of macular hole surgeries. Its removal is also associated with a reduced risk of subsequent reopening of the macular hole. ^[14] ILM peeling may be accomplished via a "rhexis" not unlike that of a capsulorrhexis in lens surgeries. Very fine forceps may be used to peel the ILM from the underlying retina. Care should be taken not to include the deeper layers in the forceps' grasp, which may further damage the surrounding retinal tissues. Currently, many surgeons use vital dyes such as indocyanine green or trypan blue to stain the ILM, making it easier to visualize and manipulate. Another ophthalmic stain, brilliant blue G (TissueBlue), was approved by the FDA in December 2019. It is a disclosing agent administered intravitreally that selectively stains the ILM. Triamcinolone acetonide is also used to assist with visualization of the ILM for peeling.

Use of an inverted ILM flap was first described in 2010 for repairing large macular holes. ^[15] This technique involves reflecting the ILM peeled from around the hole back over the hole so that it is covered with inverted ILM tissue. Many authors suspect that this technique would be beneficial for large macular holes and macular holes in patients with high myopia (ie, holes that have a low rate of closure with standard ILM peeling techniques). ^{[16, 17, 18, 15]}

The Manchester Large Macular Hole Study showed that the standard ILM peeling was very effective for macular holes up to 650 microns. The closure rate decreased from more than 90% for holes smaller than 650 microns to only 76% for holes larger than 650 microns. ^[17] The authors suggested using inverted ILM flaps for these large holes. Rizzo et al demonstrated a significant difference in hole closure rates for patients with axial eye lengths of more than 26mm (39% with ILM peeling vs 88% with ILM flap), as well as a less dramatic benefit for macular holes of more than 400 microns (79% with ILM peeling vs 96% with ILM flap). ^[19]

Epiretinal membranes, if present, also should be removed. Techniques in completing this procedure vary from surgeon to surgeon.

After careful indirect ophthalmoscopic examination of the peripheral retina for tears, a total air-fluid exchange is performed to desiccate the vitreous cavity. A nonexpansile concentration of a long-acting gas is exchanged for air. Studies have shown that a longer period of internal tamponade equated to a higher success rate.

Sterile air and varying concentrations of either perfluoropropane or sulfur hexafluoride have been used based on surgeon preference for internal tamponade. The primary difference achieved using different gases is the duration of the gas bubble and, consequently, the amount of internal tamponade achieved within the first several days after surgery. Silicone oil has also been used as an internal tamponade for patients with difficulty positioning or altitude restrictions. However, the use of silicone oil necessitates a second subsequent surgery to remove the oil. Furthermore, the visual results are not comparable to the use of gas tamponade, possibly as a result of silicone oil toxicity at the level of the photoreceptors and RPE.

Tafoya et al showed, at 1 year, a final postoperative visual acuity difference of 20/96 (LogMAR 0.208) for silicone oil eyes versus 20/44 (LogMAR 0.453) for gas treated eyes. ^[20] Lai et al also showed the visual acuity advantage of gas tamponade with a smaller difference (20/70 vs 20/50). ^[21] However, Lai et al also showed the rate of single operation closure being only 65% for silicone oil and 91% for gas tamponade. ^[21] Thus, unless limited by patient circumstances, gas tamponade for macular hole repair is preferable to silicone oil tamponade.

Controversies surrounding the surgical repair of macular holes

20-gauge versus 23-gauge versus 25-gauge vitrectomy systems

While no one system poses a significant long-term advantage, smaller gauge vitrectomy systems, with frequently self-sealing wounds, avoid induced astigmatism from suturing sclerotomies, resulting in a more rapid recovery of vision.

An initial increase in endophthalmitis appears to have been addressed by changing the means of wound construction but may still be considered a disadvantage to small gauge vitrectomy systems.

Smaller-gauge vitrectomy systems, such as 27-gauge and 25-gauge systems, lack shaft stiffness because of the smaller barrel and may also complicate the actual vitrectomy surgery for surgeons trained using 20-gauge systems.

Internal limiting membrane (ILM) peeling

ILM peeling increases the rate of hole closure 93-100%.

The rate of visual recovery was postulated to be slowed by ILM peeling, but no recent literature supports this assertion (see next bullet point).

Spiteri-Cornish et al compared peeling with not peeling ILM in a meta-analysis of 4 randomized controlled trials. The results demonstrated an effect favoring ILM peeling for macular hole closure and final visual acuity. The analysis did not identify any difference in the rate of recovery. The benefit of ILM peeling became evident even by 3 months postoperatively. ^[22]

Use of vital dyes

Indocyanine green (ICG) dye was the first vital dye used for macular surgery. There is considerable literature questioning the toxicity of ICG dye to the retina and retinal pigment epithelium (RPE). Despite the laboratory science and literature cautioning the use of ICG dye, an equal amount of literature documented good surgical and visual results. ICG dye is still used by surgeons with care taken to limit the exposure of the retina and, potentially more importantly, the RPE to the dye.

Trypan blue has also been used to stain the ILM without the literature suggesting toxicity. On the other hand, trypan blue does not appear to stain the ILM as effectively as ICG dye.

Triamcinolone acetonide has also been used to facilitate peeling of the ILM. As of 2008, it is the only surgical adjunct to peeling of the ILM that is FDA approved for use in the eyes.

Management of lamellar holes

Lamellar holes cause symptoms but minimal loss of central visual acuity. Management has historically been conservative.

Surgical intervention has been undertaken with vision loss or patient symptomology with the recent advances in small gauge vitrectomy and further experience with ILM peeling.

Garretson et al reported a series of successfully repaired lamellar macular holes, wherein 93% eyes demonstrated improved visual acuity. ^[23] The mean improvement was 3.2 Snellen lines.

Face-down positioning

Historically, strict face-down positioning had been recommended for patients for up to 4 weeks, with consequent difficulties of compliance and patient quality of life during that period.

More evaluation placed into shorter periods of face-down positioning, though, traditionally, it has been believed that the shorter the period of face-down positioning, the lower the rate of successful hole closure. In 1997, Tournambe et al described a pilot study of patients without face-down positioning. They reported a success rate with one surgery of 79% and suggested that pseudophakia was necessary for consideration of liberalization of positioning requirements.

The advent of ILM peeling has encouraged a second look at minimal to no face-down positioning. Rubinstein et al described a case series of 24 eyes of patients who underwent ILM peeling and then did not position postoperatively. ^[24] In this case series, 22 eyes were successfully closed and had visual improvement with both eyes that failed being stage 4 large holes. ^[24]

Others have reported comparable, if not better, results in patients with only 1 day of positioning. Dhawahir-Scala et al suggests that a critical factor is the size of the gas bubble on postoperative day 1 being greater than 70%. ^[25] Tranos et al showed, however, that there may be more rapid progression of cataract formation with less face-down positioning. ^[26] Tranos et al were among several authors who recommended combined phacovitrectomy for phakic patients to allow less stringent positioning requirements. ^[26] Iezzi and Kapoor reported a series of 68 eyes that underwent macular hole repair with broad ILM peeling and SF6 tamponade without any face-down positioning. They reported a 100% rate of closure with a single procedure. ^[27]

Alberti and Ia Cour compared face-down positioning with nonsupine positioning and found equivalent macular hole closure rates and noninferiority of nonsupine positioning. However, they also identified that gas fill in nonsupine positioning correlated with macular hole closure. ^{[28, 29]} These authors used perfluoropropane and ILM peeling in their study.

A different study assessed face-down positioning and withholding face-down positioning, as well as using a shorter-acting gas such as sulfurhexafluoride. ^[30] These authors determined that withholding face-down positioning (essentially nonsupine positioning) was noninferior to face-down positioning and that sulfurhexafluoride was noninferior to perfluoropropane. However, when they looked more carefully at their data, they identified risk factors for lowered macular hole closure success, including hole size larger than 400 microns, no ILM peeling, older age of patient, and hole duration of greater than 9 months. They cautioned withholding face-down positioning based on their results.

Other considerations

The use of pharmacologic adjuncts, such as a transforming growth factor-beta (TGF-beta) and autologous serum, to facilitate hole closure has not been proven to have any added benefit as compared to controls such that their use has not gained much popularity.

Morizane et al reported a series of 10 patients with refractory macular holes who were managed with autologous transplantation of ILM. These eyes represented eyes that did not respond to initial surgery with standard ILM peeling or other modifying conditions such as myopic foveoschisis or trauma. All eyes responded to this procedure. ^[31]

Surgical complications include retinal detachments, iatrogenic retinal tears, enlargement of the hole, macular light toxicity, postoperative pressure elevation, and cataractogenesis.

Postoperative pressure elevation usually can be treated pharmacologically but may sometimes require an anterior chamber or vitreous tap.

Failure of hole closure/hole reopening

Histopathologic evaluation of specimens from patients with failed initial macular hole surgery demonstrated massive proliferation of cells and newly formed collagen associated with remaining ILM. The residual ILM and the associated collagen fibrils may become the source of persistent traction that prevents macular hole closure.

Retinal detachment/iatrogenic tears

The rate of postoperative retinal detachment is reported from 2-14%. Chung et al identified that the induction of a posterior vitreous detachment during surgery was a key risk factor for the development of iatrogenic retinal breaks. They found an overall incidence of 14.6% (20 of 137 eyes) for retinal breaks. Only one retinal break (3.1%) was identified in a macular hole patient who did not require the induction of a PVD. However, only 32 of 137 eyes undergoing vitrectomy for macular hole surgery did not require this step in the procedure, owing to the underlying pathophysiology of macular holes. ^[32]

Visual field defects

Visual field defects have been noted following macular hole surgery.

They are related to dehydration of the nerve fiber layer.

The rate is reduced by shorter surgical times, lower air flow, and oblique placement of infusion cannulas caused by beveled incisions of smaller gauge vitrectomies.

Cataract formation

There is a small risk of hole reopening in the immediate postoperative period following cataract surgery.

Consideration of prophylaxis versus cystoid macular edema may reduce the risk of hole reopening after cataract surgery.

A retrospective case series by Bhatnagar et al (2007) suggest that prior or simultaneous cataract extraction may carry a better long-term visual prognosis than cataract extraction following macular hole repair due to the risk of reopening of the hole following cataract surgery. ^[33]

Because complications, such as cataracts and retinal detachment, can follow treatment for macular holes, regular examinations are necessary.