The most common primary mechanism of idiopathic full-thickness macular hole (FTMH) formation is vitreous-mediated through anteroposterior or tangential tractional forces. This mechanism may explain the relatively rare (< 1%) occurrence of FTMH formation in fellow-FTMH eyes with a preexisting posterior vitreous detachment (PVD)1 and in vitrectomized eyes (0.5% to 1.1%).2–4 Spontaneous closure of FTMH is known to occur in 2.7% to 11.5% of nonvitrectomized eyes,5,6 presumably due to release of anteroposterior vitreomacular traction (VMT), or due to bridging glial tissue proliferation. However, spontaneous formation and closure of FTMH in vitrectomized eyes is a rare occurrence given the presumed absence of anteroposterior vitreous traction.
We report three cases of FTMH formation and spontaneous closure in eyes that had previously undergone a complete pars plana vitrectomy (PPV) with PVD induction and without VMT. We also summarize the characteristics of previously reported cases of spontaneous FTMH formation and closure in vitrectomized eyes and discuss possible mechanisms.
A 47-year-old, highly myopic, white male underwent PPV and scleral buckle to repair a macula-sparing rhegmatogenous retinal detachment (Figures 1A and 1B). Three years later, he presented with a small, 189-µm FTMH and decline in vision to 20/32 following a YAG capsulotomy.7 Optical coherence tomography (OCT) showed cystic intraretinal fluid on the edges of the FTMH and preexisting, mild epiretinal membrane (ERM) without evidence of VMT (Figure 1C). The FTMH and cystic intraretinal fluid spontaneously resolved 2 months later, and visual acuity (VA) improved to 20/20. On OCT, there was complete restoration of the external limiting membrane (ELM) and ellipsoid zone (EZ). Visual acuity and retinal layer integrity on OCT remained stable during 10 years of follow-up (Figures 1D–1F).
Sequential optical coherence tomography (OCT) images in a 47-year-old male following vitrectomy and scleral buckle to repair a macula-sparing rhegmatogenous retinal detachment. Time-domain OCT image showed no traction on the fovea immediately postoperatively (A) and normal foveal anatomy 2 years postoperatively (B). A full-thickness macular hole (FTMH) with surrounding cystic intraretinal fluid developed 7 months later without evidence of vitreomacular traction; an epiretinal membrane (ERM) was present, also visualized on exam (C). During the ensuing 2 months without intervention, there was spontaneous closure of the FTMH and resolution cystic intraretinal fluid (D–E). Spectral-domain OCT 10 years later demonstrated a mild ERM and complete restoration of the integrity of the retinal layers (F).
A 65-year-old white female with a history of bilateral sarcoid-associated panuveitis underwent uncomplicated cataract surgery combined with 0.59 mg fluocinolone acetonide intravitreal implantation (Retisert; Bausch+Lomb, Rochester, NY), and PPV with ERM and internal limiting membrane (ILM) peeling in the right eye for VMT 4 years prior (Figures 2A and 2B). During the next 4 years, her inflammation remained controlled with preserved retinal layer integrity, VA of 20/40, and recurrent ERM formation in the right eye (Figure 2C). She then presented with a 1-week history of new metamorphopsia and VA decline to 20/200 in the right eye and was found to have a small 174-µm FTMH with surrounding cystic intraretinal fluid on OCT (Figure 2D). There was no associated intraocular inflammation. Repeat OCT 2 weeks later demonstrated spontaneous closure of the FTMH and VA improvement to 20/126, which further improved to 20/100 1-week later (Figure 2E). There was complete ELM restoration, but small defects persisted in the EZ.
Sequential spectral-domain optical coherence tomography images in a 65-year-old female with a history of bilateral sarcoid-associated panuveitis who underwent uncomplicated cataract surgery combined with 0.59 mg fluocinolone acetonide intravitreal implantation (Retisert; Bausch + Lomb, Rochester, NY) and vitrectomy with epiretinal membrane (ERM) and internal limiting membrane peeling in the right eye for vitreomacular traction (A). Postoperatively, there was resolution of vitreomacular traction and cystic intraretinal fluid, with formation of a recurrent ERM (B, C). Four years following vitrectomy, she had a 174-µm full-thickness macular hole (FTMH) with surrounding cystic intraretinal fluid (D). During a 2-week period, there was spontaneous closure of the FTMH, resolution of cystic intraretinal fluid, restoration of the external limiting membrane and near complete restoration of the ellipsoid zone (E).
A 61-year-old white female underwent repair of tractional retinal detachment secondary to proliferative diabetic retinopathy with PPV, endolaser, but no ILM peel. At postoperative month 2, her VA was 20/200 with mild cystic fluid and an ERM, without any residual vitreofoveal traction, as seen on multiple radial OCT scans (Figures 3 and 4A). She developed a lamellar macular hole (LMH) associated with lamellar hole epiretinal proliferation (LHEP) at postoperative month 4 that progressed to a small 48-µm FTMH at month 7, with a decrease in VA to 20/320 (Figures 4B and 4C). Two weeks later, OCT showed spontaneous closure of FTMH with formation of bridging tissue at the outer nuclear complex (ONC) (Figure 4D). One year later, vision improved to 20/200 and OCT showed a LMH configuration, LHEP, and mild cystic edema with ELM restoration but a small EZ defect (Figures 4E and 4F).
Postoperative radial optical coherence tomography scans in a 61-year-old female with a tractional retinal detachment associated with proliferative diabetic retinopathy who underwent repair with vitrectomy, endolaser, and epiretinal membrane peel but no internal limiting membrane peel. Postoperative images at 2 months following surgery show release of all traction on the fovea on multiple radial cuts.
Sequential radial optical coherence tomography (OCT) scans in 61-year-old female with a tractional retinal detachment following repair and epiretinal membrane (ERM) peel. Two months following vitrectomy, foveal contour was intact with mild cystic edema and an ERM (A). Four months postoperatively, a lamellar hole developed (B), which progressed to a full-thickness macular hole (FTMH) 7 months following vitrectomy. A narrow base with wider separation in the inner retina was consistent with lamellar macular hole formation before the FTMH. Associated lamellar hole epiretinal proliferation was visualized as a hyporeflective layer (white arrow; C). During a 2-week period, there was spontaneous closure with the appearance of bridging tissue on OCT at the level of the outer nuclear layer (yellow arrow; D). There was progressive restoration of the outer retinal bands with a small residual defect in the ellipsoid zone (red arrow; E, F).
Late formation and spontaneous closure of FTMH post-vitrectomy is rare, especially following ILM removal,8–14 and has been reported to occur 7 days to 7 years following PPV, with more than half the cases spontaneously resolving within 1 month (Table).
Formation and Spontaneous Resolution of Full-Thickness Macular Holes in Eyes Following Pars Plana Vitrectomy: Summary of Known Literature
Possible mechanisms of formation (or FTMH reopening) following vitrectomy when there is no residual anteroposterior traction or vitreous-mediated traction include any process that modifies the foveolar anatomy such as progressive ERM or LHEP formation causing new tangential traction, cystoid macular edema (CME) with coalescence of perifoveal cystoid spaces, changes in ILM elasticity, intraretinal and preretinal cellular remodeling, and resultant traction.16–18 It is unlikely that residual vitreous remnants play a role in vitrectomized eye cases unless there is residual cortical vitreous causing vitreofoveal traction.19 Schlenker et al. proposed that in eyes with CME following vitrectomy, the fluid pockets were under tension and the overlying retina stretched, which led to dehiscence in the inner retina and a LMH, progression of which in turn led to umbo dehiscence and a FTMH.8,10 Spontaneous FTMH closure has also been reported following treatment with topical ketorolac, thought to be potentiated by pharmacologically induced resolution of CME.20
Possible mechanisms for spontaneous FTMH closure after previous vitrectomy include ERM contracture and bridging glial cell proliferation. Bridging tissue as a marker of glial and Müller cell proliferation has been reported to initiate ONL and ELM regeneration and may be essential for spontaneous FTMH closure.21,22 Morawski et al. showed bridging tissue on OCT within the FTMH before closure and reported spontaneous FTMH closure was more likely with a shorter duration of symptoms and younger age.21 The role of VMT release in spontaneous FTMH closure, on the other hand, may be less significant than previously thought. Proliferation of fibrous astrocytes and contraction of inner glial cells and Müller cells has been suggested to be responsible for de novo plugging of the macular defect.23,21 PVD formation may not be essential for spontaneous FTMH closure, although overlap of PVD and glial tissue formation has been suggested to accelerate spontaneous closure. This could explain the spontaneous closure in vitrectomized eyes where an ERM can facilitate preretinal tissue proliferation and contraction around the hole margins, promoting bridging tissue formation.16 In our series, all eyes had a small FTMH (mean size: 137 µm; range: 48 µm to 189 µm) with an ERM or LHEP before FTMH formation. ILM remodeling with increased elasticity and cellular alterations following vitrectomy may also have contributed to spontaneous FTMH closure.12
Case 3 in our series had a particularly thick ERM and developed a distinct hyporeflective layer consistent with LHEP associated with LMH formation. A narrow base with wider separation in the inner retina as seen in Case 3 implies that a LMH formed before the FTMH.22 LHEP has been proposed to be a unique feature of LMH and their progression to FTMH.24 In a recent series, Tsai et al. reported that six of eight cases with spontaneous FTMH closure had OCT evidence of LHEP.22 They suggested observation for 4 weeks to 6 weeks in nonvitrectomized eyes with a FTMH associated with ERM or LHEP as the underlying mechanism. Our series suggests that these recommendations can also be applied to eyes that have already undergone a vitrectomy but have an ERM or LHEP.
In a series of 10 nonvitrectomized eyes that exhibited spontaneous FTMH closure, Morawski et al. reported ONL regeneration in all eyes, EZ regeneration in 60%, and ELM regeneration in 90%.21 In our series, we found similar findings of ONC and ELM regeneration in all three eyes, and complete EZ regeneration in one of three eyes. It has been suggested that the tangential traction presumed to be responsible for creation of ERM- and LHEP-associated FTMH may compromise photoreceptor integrity more than the anteroposterior or oblique traction associated with vitreoretinal interface.22 This could possibly explain the delayed and incomplete visual recovery in Case 2.
All three cases in our series developed a FTMH in 7 months or more following vitrectomy and demonstrated spontaneous resolution within 2 months of onset of symptoms; two cases of FTMH resolved within a 2-week period. On review of literature, an ERM was seen in nearly all cases with delayed FTMH formation and spontaneous closure post-PPV (Table). There was no reopening of the macular hole in the three eyes in our series at the 1-month and up-to-10-year follow-up.
Despite these theories, several questions remain regarding the etiology of FTMH formation in vitrectomized eyes. Anatomical features predicting those eyes that have a higher chance of spontaneous recovery need to be elucidated further. Although cases of FTMH developing in vitrectomized eyes are not common, our series illustrates that spontaneous closure is still possible despite the presence of ERM and LHEP. Rather, the presence of a mild ERM with a small FTMH may even be a favorable characteristic. In such vitrectomized eyes, observation with serial OCT measurements may be warranted to allow spontaneous closure of FTMH prior to proceeding with surgical intervention.