Since described as early has 1869 by Knapp, macular hole has been an entity of great interest for various investigators. This resulted in continuous revolutions in the underlying pathogenesis and its management. Recently OCT has emerged as most important imaging modality for prognostication and planning of surgical intervention. Most popular surgical intervention to treat macular hole is pars plana Vitrectomy with internal limiting membrane peeling with gas tamponade. This review article is focused on clinical features, pathogenesis, roles of newer imaging tools in the management of macular holes and different surgical approaches.

 

Keywords: Macula hole, Gas tamponade, ILM peeling, Brilliant blue G

 

Abbreviations: MH: Macular Hole; ERM: Epiretinal Membrane; CME: Cystoid Macular Edema; RD: Retinal Detachment; CNVM: Choroidal Neovascular Membrane; FTMH: Full Thickness Macular Hole; SD-OCT: Spectral Domain-Optical Coherence Tomography; FFA: Fundus Fluorescein Angiography; LMH: Lamellar Macular Holes; HFF: Hole Form Factor; FAF: Fundus Autofluorescence; LF: Melanolipofuscin; RPE: Retinal Pigment Epithelium; OPL: Outer Photoreceptor Layer; MPH: Macular Pseudoholes; FP: Foveal Pseudocysts; VMT: Vitreomacular Traction; ILM: Internal Limiting Membrane; BBG: Brilliant Blue G; PFCL: Perfluorocarbon Liquid; FDP: Face Down Posturing; SANFL: Swelling of the Arcuate Retinal Nerve fiber Layer; DONFL: Dissociated Optic Nerve fiber Layer

INTRODUCTION

Macular hole (MH) represents a partial or full thickness defect or dehiscence in the central retina at the umbo [1]. The prevalence rate of MH in India has been found to be 0.17% [2]. With the better understanding of pathogenesis and improvement in vitreoretinal surgical technique and instrumentation, excellent visual outcomes can be achieved.

CAUSES

Primary cause of MH in majority of cases is idiopathic. Trauma is among the most common secondary cause of macular hole. Apart from trauma, other conditions that can secondarily lead to MH are epiretinal membrane (ERM), cystoid macular edema (CME), retinal detachment(RD), proliferative diabetic retinopathy, severe hypertensive retinopathy, choroidal neovascular membrane (CNVM), juxta foveal telengiectasia, retinoschisis, lightening, photic retinopathy (electrocution, welding, accidental Nd-YAG laser) [3-6].

CLINICAL FEATURES

Idiopathic MH usually occurs in the sixth to seventh decade and women are affected more often than men; reported ratio is 2-3:1 [3]. There is no proven theory for female preponderance but recently study done with SD-OCT has shown that females has significantly thinner central foveal thickness [7]. There is 3-29% risk of fellow eye getting affected with MH [8].

SYMPTOMS

Patients with smaller MH may have no symptoms and are diagnosed on routine ophthalmoscopic evaluation. Symptomatic patients usually complain of blurred vision and metamorphopsia. Those with larger holes will have scotoma or a defect in central vision.

SIGNS

Visual acuity of the affected eye may vary according to the size, duration, location and associated sub retinal cuff of fluid. In smaller holes it may vary from 20/25-20/40 while in larger holes it may 20/80 to 20/400. 

OCT BASED PROGNOSIS

Various parameters as measured by OCT: base diameter, defect depth, central foveal thickness and perifoveal thickness help to prognosticate the subtypes of LMH. Hole form factor (HFF): It is defined as the ratio of the sum of the lengths of the two sides of macular hole to the base diameter. HFF between 0.9-1 has been correlated with better anatomical and functional outcome after surgery whereas HFF less than 0.5 are found to have poor prognosis (Figure 1) [12]. It also delineates presence and type of ERM that can decrease success rates if not dealt during surgery. Intraretinal cystic spaces shown in OCT are also considered as good prognostic factor.

The major milestone in understanding of pathogenesis of MH was classification by Gass [1]. Green proposed that chronic low-grade traction due to ocular rotation stimulates cellular proliferation of Muller cells, astrocytes and RPE realigning vitreous fibres and redirecting the fractional force in tangential direction [16].

Studies done with OCT has showed that the initial stage of MH formation starts as a triangular elevation of outer photoreceptor layer(OPL) and its detachment from RPE due to fractional forces. The traction on the fovea occurring prior to anatomic changes to the fovea has been referred to as Stage 0 and may resolve without progression in 40-50% of patients [17]. Ezra published an OCT documented study suggesting that failure of normal age-related separation of cortical vitreous from posterior pole as a result of an abnormally tenacious attachment to the fovea leads to MH formation [18].

DIFFERENTIAL DIAGNOSIS

The varied presentation of lamellar macular defect may mimic a MH. Lamellar macular defects were categorized into three different subtypes based on their OCT appearance: LMH, macular pseudo holes (MPH) and foveal pseudo cysts (FP) [19].

Lamellar holes have thin fovea resulting from avulsion of inner layer of macula.

A macular pseudo hole results from the centripetal contraction of an ERM that subsequently leads to verticalisation of the foveal slopes and a sharply punched out defect [20].

FP is described as a precursor to MH or LMH formation due to direct vitreomacular traction (VMT) [9] ERM can also result in avulsion forces leading to the formation of pseudo cyst [21].

It has been found that MPH have smaller diameter and thicker central foveal tissue, therefore they have better visual acuity than LMH and FP whereas both LMH and FP are shown to have deeper and wider intraretinal split and also thin central foveal tissue [19].

MANAGEMENT

FTMH were once considered untreatable and surgery was indicated once extensive RD occurred [22,23]. In 1991, Kelly and Wendel first demonstrated a surgical procedure to close idiopathic MH with good functional outcome [24]. Later several adjuncts like TGF-β, autologous platelet concentrate, bovine thrombus, laser barrage, etc. [25,26], currently indications of surgery are as follows:

A.      On the basis of macular hole staging and pre-op visual acuity.

1.       FTMH with stage II and above.

2.       Patients with stage III and IV with visual acuity of 6/18 or below: these patients readily gain 2 or more line improvement after surgery.

3.       Stage II macular holes with visual acuity ranges from 6/12 to 6/18 (20/40-20/60).

4.       Patients with visual acuity of >6/12 presenting with minimum symptoms like metamorphopsia and smaller hole size rarely requires surgery. Freeman et al observed spontaneous regression in 4% of all cases. Therefore, these patients can be followed up [27].

B.      As per imaging modalities.

OCT based parameters and FAF are important to prognosticate and to plan the surgery.

SURGICAL OBJECTIVE OF MACULAR HOLE SURGERY

Surgical objective of MH surgery is twofold; first to relieve tractional forces; second to activate reparative healing mechanism [28,29].

 

 

Surgical technique

Pars Plana Vitrectomy with internal limiting membrane (ILM) peel with fluid gas exchange (FGE) is the accepted technique. Earlier, 20G system and currently 27G, 25G and 23G systems have been employed [30]. Brilliant blue G (BBG) dye is used at concentration of 0.25 mg/ml for staining ILM. This dye does not stain ERM thus after removal of ERM, dye should be re-injected to look for residual ILM. This method is called as double staining and ensures complete removal of ILM [31]. Lifting of ILM has been a challenge as well as traumatic to retina [32]. Newer instruments like silicone tipped cannula; diamond duster and finesse flex loop have made ILM peeling convenient and less traumatic.

Recently many techniques have been proposed for large and refractory MH; fovea sparing ILM, free flap, inverted ILM flap with and without PFCL, cabbage technique [33-37]. All these techniques aim at stuffing macular hole with ILM. This is postulated that this ILM will serve as scaffold for retinal tissue to grow upon. There are various reports that these flaps get dislocated with fluid current and during fluid air exchange. Autologous retinal transplant has also been used to plug macular hole also provides scaffold and plugs macular hole [38].

To peel or not to peel

Studies favoring ILM peeling state that peeling removes the template upon which the glial cells proliferate. Also, it removes the tangential traction. ILM peeling serves to increase MH edge mobility and reduce MH diameter [29].

Studies which do not advocate ILM peeling postulated that removal of ILM injures the Müller cell footplates and trigger reparative gliosis [32].

ILM peeling has shown higher rate (92%) of primary closure of MH as compared with eyes undergoing MH repair without ILM peeling (82%). Late reopening of hole was also found to be higher in no ILM peeling group when compared with ILM peeling group (7% vs. 0.6 %) [39].

To posture or not to posture is still a controversial issue. Studies have reported strict face down posturing (FDP) for at least a week (24). It is thought to aid hole closure due to the buoyant force of intraocular gas bubble [40]. The gas bubble keeps the edges of macular hole dry and provides scaffold for glial cell proliferation [38,41]. Also surface tension is constant around the bubble’s interface with the retina as long as volume of gas is 2/3^rd to 3/4^th of vitreous cavity [42].

But successful hole closure without FDP as reported in Tornamby Pilot study supports the approach avoiding FDP [43]. Various other studies favored no FDP or a minimum of one day FDP and showed 90% anatomical and functional success rate [44,45].

 

Endotamponading agents

In original description of macular hole surgery, use of non- expansible gas of SF6 with 1 week FDP was indicated [23]. In patients who require long-term tamponade, cannot maintain positioning or have to travel by air, silicone oil can be opted. But its removal requires another surgery and also anatomical closure is found to be only 65% as compared with C3F8 gas which has 91% success rate [46]. C3F8 and densiron 68 share advantage of having longer effect and both do not require positioning. Densiron-68 is a mixture of silicone oil and amphiphilic perflurohexyloctane, which facilitates better contact with the retina compared with standard silicone oil [47]. Vitrectomy and air tamponade combined with 1-3 day facedown positioning produced an excellent rate of macular hole closure [42,48].

Types of macular hole closure

On the basis of postoperative OCT findings, closed macular holes have been classified into two groups:

Type 1: MH is closed without foveal defect of the neurosensory retina.

Type 2: Foveal defect of the neurosensory retina persists postoperatively although the whole rim of the MH is attached to the underlying RPE with flattening of the cuff [49].

Complications of surgery

1.       Swelling of the arcuate retinal nerve fiber layer (SANFL): The SANFL does not appear to impact the final BCVA and can be expected to disappear in about 3 months [50]. There are two hypotheses regarding the cause of SANFL [51]. The first hypothesis is that surgical forceps cause direct damage to the retina when grasping the ILM while the second is that ILM peeling causes damage to the Müller cell endplates that are attached to the ILM [51].

Dissociated optic nerve fiber layer (DONFL), which is similar to the SANFL is observed as small, spindle-shaped splitting adjacent nerve fiber bundles on SDOCT [52] Not all patients who undergo ILM peeling will present with the DONFL postoperatively, and there have been no significant differences observed between eyes with and those without the DONFL with respect to BCVA or macular sensitivity. The reason for DONFL presentation is also unclear, although some authors speculated that the DONFL is caused by irregularly distributed Müller cells following ILM peeling in regions that show a higher density of nerve fiber bundles in the RNFL.

2.       Retinal breaks: The incidence of retinal break formation during macular hole surgery is 5.5% [53].

3.       Retinal detachment.

4.       Gas cataract: The cataract progression following macular hole surgery is found to be 64% within first year. Therefore these days it is advocated to undergo combined macular hole and cataract surgery. Lens extraction also allows a more complete Vitrectomy [54].

CONCLUSION

Macular hole can be caused by several factors. Not all macular holes need surgical intervention. OCT has redefined the macular hole and its prognostication. Also with the invention of MIVS, surgical techniques and functional outcomes has been improved dramatically.

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