# Macular Hole and Epiretinal Membrane

## Macular Hole

### Pathogenesis

Full-thickness macular holes develop as a consequence of vitreomacular traction at the fovea. During the process of posterior vitreous detachment, the vitreous may separate from the surrounding retina while remaining persistently attached at the fovea. The resulting anteroposterior and tangential traction progressively disrupts the foveal architecture, eventually creating a full-thickness defect in the neurosensory retina. Risk factors include age between 60 and 80 years, female sex (with a 2:1 female-to-male predominance), and myopia. The fellow eye carries a 10 to 15% lifetime risk of developing a macular hole.

### Classification (Gass -- Historical, Now OCT-Based)

The original Gass classification, based on biomicroscopic appearance, describes four stages. Stage 1 is an impending hole, in which vitreomacular traction produces a foveal cyst without a full-thickness defect. Stage 1A presents as a foveal yellow spot from tangential traction, and Stage 1B shows a foveal yellow ring as a deeper cyst forms. Approximately 50% of Stage 1 holes resolve spontaneously when the PVD completes and traction is released. Stage 2 is a small full-thickness hole measuring less than 400 micrometers, with persistent vitreous attachment and a visible yellow ring or crescent. Stage 3 is a full-thickness hole larger than 400 micrometers in which the posterior vitreous has detached but the operculum remains attached to the posterior hyaloid face. Stage 4 is a full-thickness hole with complete PVD and a free-floating operculum in the vitreous cavity.

### OCT-Based Classification (IVTS -- International Vitreomacular Traction Study)

The modern OCT-based classification from the International Vitreomacular Traction Study Group has supplanted the Gass system. Vitreomacular adhesion (VMA) describes vitreous attachment to the macula without distortion of the retinal architecture. Vitreomacular traction (VMT) describes vitreous attachment that causes macular distortion, further subclassified as focal (attachment width of 1500 micrometers or less) or broad (greater than 1500 micrometers). Full-thickness macular holes are classified by minimum diameter: small (250 micrometers or less), medium (250 to 400 micrometers), or large (greater than 400 micrometers). Lamellar macular holes are partial-thickness defects with an irregular foveal contour and generally carry a better visual prognosis than full-thickness holes.

| IVTS Classification | Definition | Subtype | Key Features |
|---|---|---|---|
| Vitreomacular adhesion (VMA) | Vitreous attached to macula | Focal (<=1500 um) / Broad (>1500 um) | No retinal distortion |
| Vitreomacular traction (VMT) | Vitreous attached causing distortion | Focal (<=1500 um) / Broad (>1500 um) | Macular distortion present |
| Full-thickness macular hole (small) | Complete retinal defect | <=250 um diameter | Best surgical prognosis |
| Full-thickness macular hole (medium) | Complete retinal defect | 250-400 um diameter | Good surgical prognosis |
| Full-thickness macular hole (large) | Complete retinal defect | >400 um diameter | Consider inverted ILM flap |
| Lamellar macular hole | Partial-thickness defect | -- | Better visual prognosis than FTMH |

### Clinical Features

Full-thickness macular holes typically present with decreased central visual acuity, usually in the range of 20/80 to 20/400, accompanied by metamorphopsia and a central scotoma. The Watzke-Allen test, in which a thin slit-beam is projected over the fovea, is positive when the patient reports a break or thinning in the line. OCT is the definitive diagnostic tool, demonstrating the full-thickness neurosensory retinal defect, a surrounding cuff of subretinal fluid, and intraretinal cystoid changes at the hole edges.

<image>OCT B-scan through a full-thickness macular hole showing the full-thickness neurosensory retinal defect, surrounding cuff of subretinal fluid, intraretinal cystoid changes, and elevated edges with measurement of hole diameter</image>

### Surgical Management -- Pars Plana Vitrectomy

#### Technique

The standard surgical approach begins with a core vitrectomy followed by induction of a posterior vitreous detachment if one is not already present. Internal limiting membrane peeling is then performed around the hole, using staining agents such as indocyanine green, brilliant blue G, or triamcinolone acetonide to visualize the transparent ILM. Peeling a disc of ILM around the hole releases the tangential traction that keeps the hole open. For large holes measuring 400 micrometers or greater, the inverted ILM flap technique -- in which the peeled ILM is folded into the hole rather than removed -- has significantly improved closure rates. After ILM management, a fluid-air exchange is performed followed by injection of gas tamponade, typically SF6 at 20% or C3F8 at 14%. Prone (face-down) positioning is traditionally maintained for one week, though there is growing evidence that shorter positioning of three to five days may be adequate for smaller holes, and positioning may be less critical overall for small holes.

#### Outcomes

Anatomical closure rates exceed 90% for Stage 2 through 4 holes and surpass 95% when ILM peeling is performed. Most patients gain two or more lines of visual acuity, though the final vision depends on hole size and duration. Small, recently developed holes carry the best visual prognosis, while large, chronic holes may show limited visual recovery even when anatomical closure is achieved.

### Pharmacologic Vitreolysis -- Ocriplasmin (Jetrea)

Ocriplasmin is a recombinant truncated form of plasmin that cleaves laminin and fibronectin at the vitreoretinal interface. It is administered as a single intravitreal injection of 0.125 mg. The MIVI-TRUST trials demonstrated hole closure in approximately 40% of small holes (250 micrometers or less) with concurrent vitreomacular traction. Efficacy is limited for larger holes or in the absence of VMT. Side effects include photopsia, floaters, transient visual acuity decrease, dyschromatopsia, and rare but serious complications including retinal detachment and lens subluxation. The current role of ocriplasmin is narrow: it is considered for selected patients with small full-thickness macular holes of 250 micrometers or less accompanied by focal VMT. Its use has declined significantly due to modest efficacy and the concern for adverse effects.

## Epiretinal Membrane (ERM)

### Pathogenesis

Epiretinal membranes are fibrocellular proliferations that develop on the inner retinal surface, adherent to the internal limiting membrane. They are composed of glial cells (Muller cells and astrocytes), retinal pigment epithelium cells, fibroblasts, myofibroblasts, and hyalocytes. As the membrane matures, contractile elements cause the underlying retina to wrinkle and distort.

### Classification

Idiopathic (primary) epiretinal membranes are the most common type, associated with posterior vitreous detachment and advancing age. Secondary epiretinal membranes develop after retinal detachment repair, laser photocoagulation, cryotherapy, intraocular inflammation (uveitis), diabetic retinopathy, trauma, or retinal vascular disease.

### Clinical Features

Many epiretinal membranes are asymptomatic and discovered incidentally on examination. When symptomatic, the most common complaint is metamorphopsia. Visual acuity is variably affected, ranging from 20/20 to 20/200. On fundoscopy, fine macular striae produce a shimmering, cellophane-like appearance known as cellophane maculopathy. As the membrane contracts, more pronounced findings develop, including pseudohole formation, macular pucker, vascular tortuosity, and macular edema. Ectopic foveola -- displacement of the foveal center from membrane traction -- may be observed.

### OCT Features

OCT demonstrates a hyperreflective line on the inner retinal surface representing the membrane. Associated findings include retinal thickening, loss of the normal foveal contour, inner retinal wrinkling and layer distortion, intraretinal cysts or macular edema, tractional schisis (splitting of the retinal layers), and the "cotton ball" sign in cases of thick, wrinkled membranes.

<image>Fundus photograph showing epiretinal membrane with macular striae and vascular tortuosity, alongside corresponding OCT demonstrating the hyperreflective membrane on the inner retinal surface with loss of foveal contour and retinal thickening</image>

### Management

#### Observation

Observation is appropriate for asymptomatic membranes or those causing only mild symptoms with preserved visual acuity of 20/40 or better. Serial OCT monitoring confirms stability. Many epiretinal membranes remain stable for years and never require surgical intervention.

#### Surgical Intervention -- Vitrectomy with Membrane Peeling

Surgery is indicated when visual acuity declines to 20/40 or worse, when metamorphopsia is progressive, or when symptomatic distortion significantly affects the patient's quality of life. The technique involves pars plana vitrectomy followed by peeling of the epiretinal membrane with intraocular forceps, using vital dyes or triamcinolone to enhance visualization. ILM peeling is often performed simultaneously to reduce the rate of ERM recurrence to less than 5%, compared with 10 to 20% recurrence when the ILM is left intact. However, ILM peeling adds surgical complexity and may cause dissociated optic nerve fiber layer (DONFL) defects, which are typically asymptomatic. Visual acuity improves in 70 to 80% of patients, though improvement in metamorphopsia may lag behind the acuity gains.

#### Timing of Surgery

There is a growing trend toward earlier surgical intervention, as operating before chronic structural damage accumulates may yield better visual outcomes. However, since many patients do well with observation, the decision to proceed with surgery is individualized, weighing the impact of metamorphopsia on quality of life against the risks and recovery associated with vitrectomy.

## Lamellar Macular Hole

### Features

A lamellar macular hole is a partial-thickness foveal defect -- importantly, it is not a full-thickness hole. OCT shows an irregular foveal contour with loss of foveal tissue, but the outer retinal layers and photoreceptor layer remain intact. Lamellar holes are often associated with epiretinal membranes and generally maintain better visual acuity than full-thickness macular holes. They may be confused with macular pseudoholes on clinical examination.

### Management

Observation is appropriate when the hole is stable and vision is adequate. Surgical intervention with vitrectomy and ERM/ILM peeling is considered if the condition is progressive or causing significant symptoms. In some cases, lamellar holes may evolve into full-thickness macular holes over time.

## Macular Pseudohole

A macular pseudohole is a central opening in an epiretinal membrane that simulates the appearance of a true macular hole. On OCT, the key distinguishing feature is a steep foveal contour created by centripetal contraction of the surrounding ERM, but there is no full-thickness retinal defect. The foveal thickness is normal or near-normal, and visual acuity is usually preserved. Pseudoholes are generally observed; surgery is considered only if the associated epiretinal membrane becomes symptomatic.

<image>Comparative OCT images showing the differences between full-thickness macular hole, lamellar macular hole, and macular pseudohole with key distinguishing features labeled</image>

## Clinical Pearls

OCT has replaced clinical classification as the definitive tool for macular hole assessment; the minimum hole diameter should always be measured, as it is the most important factor for prognostication and surgical planning. Small holes of 250 micrometers or less carry the best surgical prognosis and represent the only candidates for ocriplasmin. The inverted ILM flap technique has been a significant advance, dramatically improving closure rates for large and myopic macular holes that previously had lower success rates. ILM peeling during ERM surgery reduces recurrence from approximately 15% to approximately 3%, but the benefit must be weighed against the added surgical complexity. The fellow eye should always be examined, as epiretinal membranes are bilateral in approximately 20% of cases, and the fellow eye risk for full-thickness macular hole is approximately 10%. Macular hole surgery in highly myopic eyes deserves particular attention, as myopic macular holes may have worse anatomical and visual outcomes compared with non-myopic eyes. DONFL defects after ILM peeling are a common finding on postoperative OCT, but they are usually asymptomatic and do not progress. Patients undergoing ERM surgery should be counseled that metamorphopsia may persist even after successful membrane removal and visual acuity improvement, as the retinal distortion from chronic membrane traction takes time to resolve and may not recover completely.

## References

- Duker JS, et al. The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology. 2013;120(12):2611-2619.
- Stalmans P, et al. Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes (MIVI-TRUST). N Engl J Med. 2012;367(7):606-615.
- Michalewska Z, et al. Inverted internal limiting membrane flap technique for large macular holes. Ophthalmology. 2010;117(10):2018-2025.
- American Academy of Ophthalmology. Basic and Clinical Science Course, Section 12: Retina and Vitreous.