Vitrectomy or Observation for Lamellar Macular Holes With Epiretinal Proliferation? A Critical Meta-Analysis

Study: Sabage LE, Miranda JVC, Antunes ABFA, Meneghete BP, Moreira-Neto CA. Vitrectomy Versus Observation for Lamellar Macular Holes With Epiretinal Proliferation: A Systematic Review and Meta-Analysis. American Journal of Ophthalmology. 2026;289:292–303. DOI: 10.1016/j.ajo.2026.05.036.

Design: PRISMA-reported systematic review and random-effects meta-analysis, prospectively registered as PROSPERO CRD420251089664. Seventeen studies comprising 610 eyes with lamellar macular hole–associated epiretinal proliferation (LHEP). Fourteen studies contributed 328 surgically treated eyes; five studies contributed 282 observed eyes. Because only two studies contained both management arms, surgery and observation were pooled separately, not as a randomized head-to-head treatment comparison.

Lamellar macular holes (LMHs) encompass distinct OCT phenotypes. LHEP is a homogeneous, moderately reflective, largely noncontractile epiretinal proliferation closely adherent to the retinal surface, unlike the conventional tractional membrane associated with ERM foveoschisis. The review focuses on LMH with LHEP; its findings should not be extrapolated to every lamellar macular defect.

Observation is often reasonable when symptoms and anatomy are stable, whereas vitrectomy is considered for progressive visual impairment or structural deterioration. The unresolved question is whether surgery offers superior outcomes over the natural course, especially given the possibility of full-thickness macular hole (FTMH) formation.

Searches covered PubMed, Embase, Scopus, Cochrane Library and Web of Science through September 2025. Adults with OCT-defined LHEP-associated LMH undergoing vitrectomy or observation were eligible. Primary outcome: change in best-corrected visual acuity (BCVA) in logMAR; secondary outcome: FTMH progression. Newcastle–Ottawa Scale and RoB 2 were used for risk-of-bias assessment.

• Study mix: predominantly retrospective case series (approximately 82%); two prospective case series and one randomized comparative pilot study.
• Follow-up: surgery 19.92 ± 14.66 months; observation 31.55 ± 15.15 months.
• Baseline acuity: surgical studies approximately 0.45 logMAR; observational studies approximately 0.35 logMAR.
• Risk of bias: Newcastle–Ottawa scores 4–7; the randomized pilot was rated as having some concerns.

The review calculated within-group pooled changes and event proportions. These estimates do not adjust for the clinical differences between patients selected for surgery and those selected for observation.

Vitrectomy: Pooled BCVA change −0.170 logMAR (95% CI −0.254 to −0.086; P < .001; I² = 0%), consistent with approximately 1.7 ETDRS lines of improvement on average. Mean acuity across surgical studies was about 0.45 logMAR at baseline and 0.29 logMAR at final assessment.

Observation: Reported pooled change −0.029 logMAR (95% CI −0.118 to +0.176; P = .695; I² = 0%), without a statistically significant change. The article also describes average baseline and final acuity around 0.35 and 0.39 logMAR, respectively; these descriptive values and the reported pooled effect should not be treated as interchangeable estimates.

Interpretation: Improvement after vitrectomy is a consistent association within treated cohorts, but the difference between separate pooled groups is not a valid direct estimate of surgical superiority. Baseline severity, selection for surgery, follow-up, cataract extraction and technique may influence the observed changes.

Unadjusted pooled FTMH event proportions: 7.5% after vitrectomy (95% CI 4.0%–13.6%) and 4.2% during observation (95% CI 1.4%–11.8%). The confidence intervals overlap and follow-up duration differs between groups. These figures cannot establish equivalent risk or prove that surgery does not increase FTMH formation.

Exploratory trim-and-fill estimates: 12.4% after vitrectomy (95% CI 7.4%–20.1%) and 10.1% with observation (95% CI 3.3%–27.2%). These are sensitivity analyses based on imputed hypothetical studies, not observed event rates or a formal adjusted comparison between treatments. The observational estimate is especially uncertain.

The paper’s forest plots display the within-cohort event estimates separately; the data do not support an individual patient’s absolute risk without considering OCT features, follow-up and selection factors.

Decision-making should integrate symptoms, BCVA trajectory and serial OCT. Relevant OCT features include ellipsoid-zone (EZ) integrity, enlargement of the lamellar defect, foveal contour, retinal thickness and the extent of epiretinal proliferation. Progressive structural damage or disabling metamorphopsia may favor discussion of surgery; stable anatomy with satisfactory function supports continued monitoring.

Reported surgical methods varied, including conventional internal limiting membrane (ILM) peeling, foveal-sparing peeling and embedding/repositioning of proliferative tissue into the lamellar defect. This review cannot identify a single superior technique. The authors discuss Müller-cell-associated tissue remodeling as a possible explanation for some postoperative anatomical recovery, but it is not established as a causal mechanism by this meta-analysis.

• Observe: Eyes with good or acceptable vision, limited symptoms and stable OCT morphology, with periodic BCVA and structural OCT assessment.
• Consider vitrectomy: Eyes with meaningful visual decline, persistent metamorphopsia, progressive defect enlargement or adverse OCT features, after individualized counseling by an experienced vitreoretinal surgeon.
• Discuss uncertainty: An average postoperative visual gain is plausible, but not guaranteed; FTMH can occur in either management pathway, and this evidence does not quantify the causal risk difference.
• Account for lens status: Concurrent or subsequent cataract surgery may contribute to visual gains and complicates attribution to vitrectomy alone.

These findings inform shared decision-making rather than mandate surgery for all LHEP-associated LMHs.

• No robust direct comparison: Only two studies contained both treatment arms, and most evidence came from uncontrolled retrospective series. Separate pooled effects cannot be interpreted as a between-treatment effect.
• Confounding by indication: Patients offered surgery commonly had worse symptoms or progressive OCT abnormalities, making the groups clinically nonexchangeable.
• Different follow-up: Approximately 20 months after surgery versus 32 months during observation; FTMH events may be missed or captured differently.
• Heterogeneous operations: ILM peeling strategies, LHEP embedding, tamponade and cataract procedures were not standardized. Phacoemulsification timing was incompletely reported.
• Small-study and reporting issues: English-only inclusion, limited randomized evidence, possible publication bias, imputed variance assumptions and sparse FTMH events weaken certainty. Low I² does not eliminate clinical heterogeneity.
• Internal reporting caution: The article describes some Egger-test findings as statistically significant despite reporting P values above .05 (for example P = .087 and P = .192). These should be interpreted as, at most, suggestive asymmetry rather than conventional statistical significance.
• Limited patient-centered outcomes: Metamorphopsia, quality of life and standardized long-term structural recovery were not consistently evaluated.

This synthesis supports a clinically relevant association between vitrectomy and improved visual acuity in selected LHEP-associated LMHs. It does not establish that vitrectomy is superior to observation, nor that FTMH risks are equivalent, because the two pathways were largely analyzed in different nonrandomized populations. Serial OCT, symptoms, baseline function and informed patient preference remain central to management. Prospective, directly comparative studies with standardized OCT definitions, surgical protocols, lens-status adjustment and matched follow-up are needed.