Justin L. Gottlieb
Advances in vitreoretinal imaging techniques and success in surgical repair have stimulated great interest in the pathophysiology and natural history of macular holes. In particular, optical coherence tomography (OCT) provides unique imaging of the vitreomacular interface that has refined the understanding of macular hole formation. In the 25 years since Kelly and Wendel's landmark publication describing the successful repair of macular holes with vitrectomy surgery,[1] the surgical technique continues to be refined with improved anatomic and visual outcomes.
EPIDEMIOLOGY AND RISK FACTORS
Macular holes have been reported in association with many causes, including trauma,[2] laser treatment,[3] retinal vascular disease,[4,5] retinal detachment repair,[6,7] lightening,[8] and electrocution,[9] but the vast majority of cases are age-related and idiopathic, unrelated to other antecedent events or other ocular disease. The Eye Disease Case-Control Study Group reported that 72% of idiopathic holes occurred in women and more than 50% in patients 65-74 years of age[10] The observed increased risk in females is poorly understood and explanations only speculative. Investigating the increased incidence of macular hole in females, the case study report found that estrogen use was protective but did not find an association with prior hysterectomy. The observation of macular holes among siblings within four different families has also suggested a possible genetic component in the formation of macular holes.[11]
The risk of full-thickness macular hole formation in the fellow eye is estimated to be ~10-15%.[12-15] Normal fellow eyes with posterior vitreous detachment appear to be at a very low risk of macular hole development.[14,16] However, in fellow eyes with persistent vitreofoveal attachments (as evidenced by optical coherence tomography) 11% of fellow eyes developed a full-thickness macular hole over a 2 year period of observation.[17]
PATHOGENESIS
Theories from the early nineteenth century of the pathogenesis of macular hole focused on trauma,[18] although contemporary reports find that greater than 80% are idiopathic.[19] Early histological description of full-thickness hole noted cystic intraretinal changes.[20,21] These changes were usually assumed to be due to ocular trauma, supporting the prevailing theories of the era.
Other early theories of macular hole formation suggested that macular cysts may form atraumatically and degenerate into macular holes.[22,23] Kuhnt implicated a degenerated fovea as the cause of macular hole and termed this disorder retinitis atrophicans sive rarificans centralis.[22] The implication of cystoid degeneration, coalescence of cystic spaces, and the development of a full-thickness hole was an important development in the understanding of macular hole development, as it emphasized that trauma was not a necessary precedent event.[24]
Current concepts of macular hole formation focus on the role of the vitreomacular interface. As early as 1924, Lister stated the importance of the vitreous in the pathogenesis of macular hole,[25] noting traction of fibrous bands in the vitreous. However, he was puzzled by his own clinical observations of a lack of visible tractional vitreous bands in cases of macular holes.[26] Several series from the 1960s described signs of vitreomacular traction contributing to macular hole formation.[27-30]
Avila and Jalkh concluded that persistent vitreous-to-macula traction was important in the formation of macular holes, as 53% of their cases of macular holes did not have a posterior vitreous detachment demonstrable on biomicroscopic examination.[31] Similarly, Akiba et al described the progression of premacular hole lesions to fully developed holes without the occurrence of a posterior vitreous detachment.[32] In contrast, McDonnell et al noted a complete vitreous separation in all macular hole cases and in all cases observed to progress from premacular hole lesions to full-thickness macular hole,[33] concluding that the act of vitreous separation from the macula was critical to the formation of a full-thickness hole. It is interesting that each group concluded that vitreous traction on the macula was important in the pathogenesis of macular holes, but arriving at this conclusion from seemingly contradicting evidence.
The current concept of macular hole pathogenesis has grown from the understanding that vitreofoveal traction is central to the development of and progression to a full-thickness macular hole. In 1988, Gass[31] and Johnson and Gass[35] proposed a new hypothesis of macular hole formation, including a classification scheme for idiopathic holes and precursor lesions. This classification scheme has guided the description of macular hole development and theories of pathogenesis since that time. Gass proposed that contraction of prefoveolar cortical vitreous resulted in tangential traction. This traction resulted in a predictable progression through multiple stages of development (Fig. 155.1). Stage 1 is the earliest biomicroscopic sign of an impending macular hole and results from a foveolar or foveal detachment. Ophthalmoscopically, it appears as a yellow dot (stage 1a) or yellow ring (stage 1b), respectively (Fig. 155.2). Progressive tangential traction may result in a small full-thickness break in the neurosensory retina. These holes were described as eccentric can-opener shaped tears or small central defects (stage 2) (Fig. 155.3). These small holes usually progressed to larger 400-500 ?m holes with or without operculum (stage 3) (Fig. 155.4) and finally may involve the separation of the posterior vitreous (stage 4) (Fig. 155.5).
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FIGURE 155.1 Schematic diagram of stages of development of idiopathic macular hole based on biomicroscopic observations as proposed by Gass. See text for detail. |
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FIGURE 155.2 (a) Color fundus photograph of stage 1b hole. Note the central yellow ring. (b) Optical coherence tomography of stage 1 hole. Note the foveolar detachment. Visual acuity was 20/25. This eye later developed a full-thickness macular hole. |
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FIGURE 155.3 (a) Color fundus photograph of stage 2 macular hole. The hole is full-thickness but a diameter less than 400 ?m. (b) Optical coherence tomograph of stage 2 macular hole. Note the vitreous traction on the operculum which is not yet detached from the retina. |
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FIGURE 155.4 (a) Color fundus photograph of a stage 3 hole. This hole is at least 400 ?m in diameter and has an overlying pseudo-operculum. (b) Optical coherence tomography of stage 3 hole. In comparison to Figure 155.3b, the operculum is clearly detached form the retina surface and attached to the posterior vitreous. |
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FIGURE 155.5 Color fundus photograph of stage 4 hole. This hole was present for at least 1 year and the visual acuity had decreased to 20/200. |
Dr Gass later provided a revision and update of the biomicroscopic classification.[36] In this reappraisal, Gass proposed that the yellow ring of a stage 1b hole is due to centrifugal displacement of retinal receptors after a dehiscence at the umbo. The occult hole may be hidden by the semiopaque prefoveolar condensed vitreous cortex bridging the hole. The occult hole may then become visible after an early separation or an eccentric can-open-like tear in the condensed prefoveolar vitreous cortex. The prefoveolar cortex may then form a prehole pseudo-operculum. This scheme helped to unify surgical observations of restoration of foveal architecture and sometimes near normal function, which seemed at odds with the earlier scheme of pathogenesis in which foveal opercula containing photoreceptors were thought to develop (Fig. 155.1).
MACULAR HOLE IMAGING AND PATHOGENESIS
The classification scheme and description of pathogenesis provided by Dr Gass was based primarily on biomicroscopic observations. Other diagnostic studies may be used to help establish the diagnosis of macula hole, although the biomicroscopic appearance remains the primary means of diagnosis. Fluorescein angiography may show focal hyperfluorescence in stage 1 and stage 2 holes.[34] However, a similar pattern may be present in lesions mimicking macular holes, such as epiretinal membrane with pseudohole. B-scan ultrasonography is an excellent means of imaging the posterior vitreous hyaloid and may help determine the presence of persistent vitreous attachment to the macula.[14,37,38] It is rarely utilized to determine the presence of macular hole in clinical practice and except for the determination of posterior vitreous detachment, is not useful for staging macular holes.
Ocular coherence tomography (OCT) is a medical imaging technology that has improved the imaging of both the neurosensory retina and vitreoretinal interface.[39] OCT has especially improved visualization of very shallow detachments of the posterior hyaloid over the macula. Even with contact lens biomicroscopy this shallow detachment over the parafovea and macula is most often imperceptible. Information gained from OCT evaluation of macular hole formation in evolution has provided new understandings of the sequence of events leading from vitreofoveal traction to full-thickness macular hole formation. Gaudric et al[40] utilized OCT to study eyes with macular holes as well at the fellow eyes to detect the initial stages of vitreous separation. They were able to demonstrate initial stages of vitreous separation in the peripheral portions of the macula which then spread throughout the macula with the hyaloid remaining focally adherent to the foveola and the optic disk. A distinct convexity was observed, suggesting antero-posterior traction from the vitreous (Figs 155.2b, 155.3b, 155.4b, and 155.6). Other investigators have confirmed the ability of OCT to detect the perifoveal vitreous detachment.[41,42,43]
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FIGURE 155.6 Schematic diagram of macular hole formation based on optical coherence tomography observations. |
Johnson and co-workers[44] utilized B-scan ultrasonography and vitreoretinal surgical observations of eyes with stage 1 or stage 2 macular holes. They demonstrated the presence of a shallow, localized detachment of perifoveal vitreous typically extending to the temporal vascular arcades, supporting the findings of Gaudric. The elegant findings of investigators using OCT[40-42] and B-scan ultrasonography[14,44] suggest a modified theory of macular hole pathogenesis implicating age-related posterior vitreous detachment beginning in the perifoveal region with abnormally strong persistent vitreofoveal adherence. This theory implicates anteroposterior traction, not the tangential traction as suggested by Gass.[34,36,45] Smiddy and Flynn[46] present a unifying theory incorporating observations of early cystic degeneration, attempted wound healing by Müller and glial cells creating tangential traction, and later anteroposterior traction as clearly seen in OCT imaging. They suggest that it is possible that the weakened or dehisced central fovea may be a primary event, followed by attempted repair by focal proliferation of Müller and glial cells, and persistent anteroposterior traction at the foveola finally resulting in an irreversible development of full-thickness hole.
Staging systems utilizing the observations from OCT have been developed. These generally retain the Gass biomicroscopic stages 1A/1B through four as a basis.[47]
NATURAL HISTORY
There is a wide range of variation in the stated progression of pre-hole (stage 1 or macular 'cyst') lesions to full-thickness hole formation. The Vitrectomy for Prevention of Macular Hole Study Group[48]reported that 40% of eyes with stage 1 lesions randomized to observation progressed to full-thickness macular hole over 2 years. This occurred in an average time of 4.1 months after diagnosis. Other studies are mostly small and retrospective. Rates of progression from premacular hole lesions to full-thickness holes range from ~10 to 70%.[35,36,48,49]
Generally, spontaneous resolution of stage 1 lesions is associated with a vitreofoveal separation with foveal reattachment and a normal biomicroscopic appearance, or may demonstrate an inner lamellar hole.[36]
Visual symptoms in stage 1 or early stage 2 lesions include metamorphopsia and reduced visual acuity. The visual acuity of eyes with stage 1 macular holes may help to predict the progression to full-thickness hole formation. The visual acuity of most stage 1 lesions ranges from 20/25 to 20/80. In one retrospective series, if the visual acuity was 20/40 or better, 23% progressed to a macular hole within 2 years, whereas, if the visual acuity was 20/50 or worse, 89% progressed to macular hole.[19] The Vitrectomy for Prevention of Macular Hole Study Group similarly found that stage 1 macular holes with best-corrected visual acuity of 20/50 to 20/80 had a 66% rate of progression, while eyes with best-corrected visual acuity of 20/25 to 20/40 had a 30% risk of progression to full-thickness macular hole.[48]
The majority of stage 2 holes continue to progress to stage 3 or stage 4 holes.[50,51] Stage 3 macular holes have central visual acuity loss to the 20/80 to 20/200 level.[51] There is a strong co-relation between macular hole diameter and visual acuity.[51,52] Similarly, the hole diameter (and visual acuity) is closely correlated to duration of symptoms.
DIFFERENTIAL DIAGNOSIS
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Several lesions may simulate a full-thickness macular hole or a precursor macular hole lesion (stage 1a or 1b). The most common lesion to be mistaken for a full-thickness macular hole is an epiretinal membrane and pseudohole.[53] Also simulating a full-thickness macular hole may be a lamellar macular hole[54] or chronic cystic macular edema.
Premacular hole lesions are often misdiagnosed. Gass and Joondeph[55] reported that only one of 18 patients referred with a diagnosis of stage 1 lesion actually had such a lesion. The other misdiagnosed lesions included aborted macular hole, stage 2 holes, stage 3 holes, and unrelated lesions. Other lesions simulating a 'pre-hole' lesion may include central serous chorioretinopathy with a central yellow spot,[55] the early yellow lesion of solar retinopathy,[55] a central druse in age-related macular degeneration,[55] or a pseudo-operculum.[56]
MANAGEMENT OF MACULAR HOLES
Because of the preservation of peripheral vision and the relative rarity of bilateral central visual loss, some have questioned the necessity for surgical intervention for repair of macular holes.[57] However, the improvements in surgical techniques and results and a concomitant decrease in overall surgical complications of vitreoretinal surgery have led most vitreoretinal surgeons to readily recommend surgical repair for affected eyes. Most retina specialists now recommend surgery for symptomatic stage 2, 3, or 4 macular holes of limited duration with visual acuity of at least 20/50 or worse.
Appreciating the role of vitreomacular traction in macular hole formation led to the first attempts at macular hole repair through pars plana vitrectomy surgery. In 1991, Kelly and Wendel reported on pars plana vitrectomy, removal of the posterior cortical vitreous, and strict facedown positioning after gas-fluid exchange for repair of macular hole.[1] The original technique of Kelly and Wendel remains the basis of surgical technique today.
The critical component of the surgical repair macular holes is the induction of a posterior vitreous detachment (Fig. 155.7). This is confirmed intraoperatively by the identification of a Weiss ring and the visualization of the more opaque posterior cortical vitreous face of the vitreous. The posterior cortical vitreous may be identified with the use of a soft silicone extrusion cannula. With gentle aspiration, the silicone tip will engage the posterior cortical vitreous and induce a bend in the tip similar to a 'fish-strike' on a fishing line.[1] Many surgeons simply use the vitrectomy cutting instrument on aspiration mode to engage and elevate the posterior cortical vitreous, prior to carefully completing the vitrectomy to the vitreous base. Epiretinal membranes are then generally excised using a barbed microvitreoretinal blade, diamond-dusted silicone scraper and/or fine intraocular forceps. Indirect ophthalmoscopy of the retina is performed to carefully inspect for iatrogenic retinal tears, most often associated with the process of vitreous separation.[58] A fluid-air exchange is performed, followed by a second fluid aspiration at least 10 min after the initial fluid-air exchange. The second aspiration allows for removal of the preretinal fluid accumulating from the residual vitreous skirt, ciliary body, and anterior-segment structures.[59] The air is then exchanged with a longer acting, nonexpansile concentration of gas. Face-down positioning is required postoperatively to provide maximum tamponade of the gas upon the surface of the macula and to stimulate closure of the macular hole.
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FIGURE 155.7 Basic steps in vitrectomy surgery for macular hole. (a) Engagement of posterior cortical vitreous (CV) with a soft-tipped extrusion cannula during active aspiration - 'the fish-strike sign'. (b) Stripping of the CV. (c) Completion of the posterior vitrectomy with the vitreous cutter. (d) Fluid-air exchange. (e) Completion of fluid-air exchange with removal of fluid over the optic nerve. |
In the initial report of successful macular hole surgery by Kelly and Wendel, 58% of the holes were successfully closed and visual acuity improvement by two or more lines occurred in 42% (73% of anatomically successful eyes). In a second report, Wendel and co-authors reported improved success with 73% anatomic success and 55% improvement by two or more lines.[60] The authors noted greater success in holes present for less than 6 months. The greater success with holes present for shorter duration has been confirmed by a number of other authors.[61,62]
Most reports of visual and anatomic results are small and uncontrolled. The definitions of anatomic and visual success differ among the many reports. Two multicenter, randomized clinical trials provide information regarding success rates. Kim and colleagues reported the results of surgery for stage 2 macular holes.[63] There was no statistically significant difference in ETDRS chart visual acuity between the surgical and observed groups. However, the Bailey-Love word-reading test did show a significant difference between the two groups (20/78 vs 20/135, P = 0.006).
In a second report from the Vitrectomy for Treatment of Macular Hole Study Group, Freeman and colleagues reported the results of surgery versus observation for stages 3 and 4 macular holes.[64] They report a 69% closure rate, as compared with a 2% spontaneous closure rate in the observation group. The surgically repaired eyes had a statistically significant better visual acuity at 6 months, both by ETDRS chart testing (20/115 versus. 20/166, P ? 0.004) and by Bailey-Love word-reading test (20/155 vs 20/166, P=<0.01).
A 2 year randomized clinical trial from Moorefields Eye Hospital compared surgery to observation for full-thickness macular holes of less than or equal to 9 months duration.[65] They additionally compared whether the addition of autologous serum improved results in the surgical arm. They reported an 11.5% spontaneous closure rate with little or no visual acuity change of those eyes at 24 months. The surgical group had an overall closure rate of 80.6%, with 45% of eyes achieving a visual acuity of 20/40 or greater. Autologous serum did not affect the anatomic or visual results.
CONTROVERSIES IN MACULAR HOLE REPAIR SURGERY
SURGICAL ADJUVANTS
Most surgeons do not currently use adjuvant agents in the surgical repair of macular holes. Such adjuvants are generally applied to the surface of the macular hole at the conclusion of vitrectomy surgery and fluid-air exchange and still require face-down positioning after an initial period of prone positioning. Glaser et al reported initial success with intravitreal transforming growth factor beta (TGF-?) derived from bovine bone with higher anatomic closure rate compared with placebo.[66] However TGF-? derived from recombinant DNA did not result in similar success.[67]
Other blood-derived adjuvants, such as autologous serum,[65,68] autologous concentrated platelets,[69] and whole blood[70] have also been utilized. Randomized clinical trials using autologous serum have not demonstrated improved closure rates or visual results.[65,68] Similarly, platelet concentrates and whole blood have not proven effective in clinical trials.
INTERNAL LIMITING MEMBRANE PEEL
Currently, the greatest controversy in surgical technique for macular hole is the role of internal limiting membrane (ILM) peeling. The necessity, preferred technique, and potential complications, including toxicity of adjuvant agents are far from definitively established.
Techniques for removal of the ILM involve establishing an elevated edge of the ILM and then peeling the ILM from around the macular hole. Establishing an initial edge may be accomplished with the use of a barbed microvitreoretinal blade[71] or with the use of fine intraocular end-grasping forceps to 'pinch' and elevate the ILM.[72] The ILM peel is most often performed in a circular motion around the hole ('maculorhexis') (Fig. 155.8).[73]
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FIGURE 155.8 Peeling the internal limiting membrane with forceps in a circular fashion around the macular hole - 'macculorhexis'. |
Removal of the ILM appears to increase the rate of macular hole closure and perhaps improve the final visual acuity. Closure rates as high as 88-100% have been reported.[71-75] However, no prospective, randomized trials have been performed to compare standard procedures with and without ILM peeling. A retrospective comparative study of hole closure rate and postoperative visual acuities did not demonstrate a statistical difference in outcomes.[76]
The identification and peeling of the ILM is technically challenging. Adjuvants to improve visualization of the ILM include indocyanine green dye (ICG), trypan blue dye, and triamcinolone acetonide.
Indocyanine green dye is instilled onto the surface of the retina in an air-or fluid-filled eye. The ICG selectively stains the ILM, and the ILM may be more easily identified and elevated with the use of diamond-dusted silicone cannula or with fine end-grasping forceps (Fig. 155.9). Retinal and retinal pigment epithelial toxicity[77-79] have been reported and questions have arisen about potentially diminished visual acuity in eyes exposed to intravitreal ICG dye.[80] Others report excellent results with the use of adjunctive-ICG without evidence of toxicity.[81] No randomized, prospective trials have been performed.
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FIGURE 155.9 Intraoperative photograph of peeling of the internal limiting membrane after staining with indocyanine green dye. |
Trypan blue stains both the ILM and epiretinal membranes. The staining of the ILM is less intense than the staining achieved with ICG.[82,83] There have been no reports of toxicity associated with trypan blue.
Triamcinolone acetonide can be injected intraoperatively onto the surface of the macula. While it does not stain the internal membrane, it adheres to the surface and may facilitate identification of the ILM.[84,85]
DURATION OF FACE-DOWN POSITIONING
Currently most vitreoretinal surgeons recommend strict face-down positioning for at least 1 week postoperatively. Compliance with positioning seems to increase the success rates of hole closure.[60] Studies of decreased duration suggest that successful closure of holes can occur with 0-4 days of positioning.[86,87] The shorter duration of positioning depends on a very complete vitreous removal in a pseudophakic eye and successful ILM peeling.[87]
The use of silicone oil for postoperative tamponade has been advocated for patients unable to position. The visual acuity and closure rates are better among eyes undergoing surgery with gas tamponade compared with silicone oil.[88,89]
COMPLICATIONS OF MACULAR HOLE SURGERY
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The most common complication of macular hole surgery is cataract formation.[90,91,92] Phakic patients undergoing macular hole surgery should be advised that cataract extraction surgery will likely be required within 1-2 years after macular hole surgery. Other surgical complications include intraoperative iatrogenic retinal tears (3-17%),[74,93,94] postoperative retinal detachment (1-5% in most reports, but up to 14% reported).[74-76,87,93,95] Postoperative retinal detachments are most typically inferiorly located and associated with small retinal tears at the vitreous base. Visual-field loss (up to 20%),[96,97] may be due to excessive infusion pressures and retinal dehydration during fluid-air exchange.[98,99] Elevated intraocular pressures are common after vitrectomy surgery with intraocular gas infusions[100] and angle closure in the unoperated eye during face-down positioning has been reported.[101]
SUMMARY
Full-thickness macular holes are most often unilateral, age-related, and idiopathic. Visual symptoms include central metamorphopsia and reduced visual acuity. Improved understanding of the pathophysiology of macular holes has occurred through careful biomicroscopic observations and through the improved visualization of the vitreoretinal interface provided by OCT. Vitreoretinal surgical techniques continue to evolve, and there remain questions as to the best surgical approach to macular holes. However, surgery most often results in successful closure of the macular hole and improvement of visual function. Vision-targeted health status questionnaires demonstrate that successful macular hole closure is associated with significant improvement in patients' vision-related quality of life, even when there is only modest improvement in visual acuity.[102]
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