The Effect of Macular Hole Duration on Surgical Outcomes: An Individual Participant Data Study of Randomized Controlled Trials

Declan C. Murphy, Mo Al-Zubaidy , Noemi Lois, Neil Scott, David H Steel* (Corresponding Author), Jinfeng Qu, Mingwei Zhao, Srinivas Sadda, Sreekumar Manasa, Divya Agarwal, Atul Kumar, Prateek Kakkar, Serge Bourgault, Eric Tourville, Raul Velez-Montoya, Sergio E. Hernandez-Da Mota, J. Abdel Ramirez-Estudillo, Jerzy Nawrocki, Zofia Anna Nawrocka, Clemens LangeJames Bainbridge, David Yorston, Mark Alberti, Morten la Cour, Ulrik Christensen, Kwok Kwan Ho Alvin, Macular Hole Duration Study Group

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Topic: To define the effect of symptom duration on outcomes in people undergoing surgery for idiopathic full thickness macular holes (iFTMH) by means of an individual participant data (IPD) study of randomised controlled trials (RCT). The outcomes assessed were primary iFTMH closure and post-operative best corrected visual acuity (BCVA)

Clinical relevance: iFTMH are visually disabling with a prevalence of up to 0.5%. Untreated BCVA is typically reduced to 20/200. Surgery can close holes and improve vision. Symptom duration is thought to affect outcomes with surgery, but the effect unclear.

Methods: A systematic review identified eligible RCTs which included adults with iFTMH undergoing vitrectomy with gas tamponade where symptom duration, primary iFTMH closure and post-operative BCVA were recorded. Bibliographic databases were searched for articles published between 2000 and 2020. IPD was requested from eligible studies.

Results: 20 eligible RCTs were identified. Data was requested from all studies and obtained from 12 representing 940 eyes in total. Median symptom duration was 6-months (interquartile (IQR) range 3-10).

Primary closure was achieved in 81.5% of eyes. The was a linear relationship between predicted probability of closure and symptom duration. Multilevel logistic regression showed each additional month of duration was associated with 0.965 times lower odds of closure (95% CI: 0.935 to 0.996, p=0.026). Internal limiting membrane (ILM) peeling, intra-operative ILM flap use, better pre-operative BCVA, face-down positioning and smaller iFTMH size were associated with increased odds of primary closure.

Mean post-operative BCVA in eyes achieving primary closure was 0.52 logMAR (20/66). Multilevel logistic regression showed for eyes achieving primary iFTMH closure, each additional month of symptom duration was associated with worsening BCVA by 0.008 logMAR units (95% CI: 0.005 to 0.011, p<0.001) (i.e., approximately 1 ETDRS letter loss per two months). ILM flaps, intra-ocular tamponade using long-acting gas, better pre-operative BCVA, smaller iFTMH size and phakic status were also associated with improved post-operative BCVA.


Symptom duration was independently associated with both anatomical and visual outcomes in persons undergoing surgery for iFTMH. Time to surgery for iFTMHs should be minimised and care pathways designed to enable this.
Original languageEnglish
Pages (from-to)152-163
Number of pages12
Issue number2
Early online date19 Jan 2023
Publication statusPublished - 1 Feb 2023


  • Macular hole
  • randomised controlled trial
  • symptom duration
  • closure
  • visual acuity
  • individual participant analysis


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