New theory may address idiopathic macular holes

The evaluation of multiple optical coherence tomography images supports the combined tractional-hydration theory of idiopathic macular hole formation, progression, and closure.

Take-home message: The evaluation of multiple optical coherence tomography images supports the combined tractional-hydration theory of idiopathic macular hole formation, progression, and closure.


By Laird Harrison; Reviewed by Ronald C. Gentile, MD

New York-The development of idiopathic macular holes can be divided into three distinct phases and one pivotal event involving both tractional and hydration forces, according to Ronald C. Gentile, MD.

The exact pathogenesis of macular holes has long puzzled researchers. Theories have included inner retinal degeneration, glial migration, tangential and anterior-posterior (A-P) traction, hydrodynamics, and hydration, said Dr. Gentile, professor of ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York.

In studying serial optical coherence tomography (OCT) images and clinical data on 115 eyes over 15 years, Dr. Gentile and his colleagues have found clues that macular holes require a traction mediated pivotal event and that hydration and tractional forces promoting hole progression are counteracted by the dehydration forces of the retinal pigment epithelium (RPE) pump. The force that prevails will determine whether a macular hole develops.

Cystoid dehydration

The researchers also propose a concept called cystoid dehydration as a mechanism to promote macular hole closure. They described examples in which cystoid dehydration can successfully close macular holes and result in external limiting membrane (ELM) repair.


“ELM reconstitution or repair is required for the hole to close and/or stay closed,” Dr. Gentile said. “Even though this can occur after cystoid dehydration with topical treatment, in some eyes, it most often is observed surgically by utilizing the lateral capillary forces of the intraocular tamponade, a concept proposed and popularized by Vincent Reppucci, MD.”

The three phases of the theory are:

  • I. Initiating: Initiation or A-P traction phase of Johnson

  • II. Progression: Progression or cystoid hydration phase of Tornambe

  • III. Closure: Dehydration and closure phase (external limiting membrane repair)

Phase I

In phase I, A-P traction on the foveola occurs as the cortical vitreous separates from it, a concept proposed by Robert N. Johnson, MD, in 2001, Dr. Gentile said.

Phase II

To progress from phase I to phase II, Dr. Gentile believes a pivotal event is necessary that includes a break in both the inner and external limiting membrane (ILM and ELM).

“Of note, the pivotal event can occur with or without separation of the vitreous from the fovea,” he said. “And phase II can occur with or without evidence of further vitreofoveal traction.”

If phase I occurs, and the hyaloid releases from the foveola without entering phase II, Dr. Gentile considers the macular hole to be “aborted,” a term used in some of the seminal work by the late J. Donald M. Gass, MD, more than 25 years ago.


Dr. Gentile described the case of a 70-year-old woman who presented with a tiny yellow scotoma for 2 days. OCT showed vitreofoveal separation with a small defect in the ILM.

The initial foveolar defect resulted in destabilization of the foveola with progressive hydration, a concept initially proposed by Paul Tornambe, MD, in 2003, Dr. Gentile noted. During cystic formation, the macula hole enlarged as the edges of the hole elevated from the RPE with an increasing cuff of subretinal fluid.

Once a full thickness hole forms, it can enter phase III. This phase most often requires surgery, but closure can occasionally occur spontaneously or be medically prompted via cystoid dehydration, Dr. Gentile said.

Phase III

Phase III starts with cystoids dehydration. In one example, the foveal pit returned to its normal contour following surgical repair with a 20% SF6 gas tamponade. Cystoid dehydration occurs prior to repair or reconstitution of the ELM and reabsorption of the subretinal fluid of subfoveal lucency, Dr. Gentile said.

In another case, Dr. Gentile administered topical treatment to promote cystoid dehydration in an 85-year-old man with a small macular hole and extensive cystoid hydration. Fluorescein angiography before treatment revealed no significant late leakage.

Treatment included a topical carbonic anhydrase inhibitor, with both steroidal and non-steroidal anti-inflammatories.

Dr. Gentile observed a decrease in cystoid hydration by about 100 µm in 1 week and resolution of the cystoid hydration by 2 weeks with closure of the hole. (Figure 1)

A small amount of subretinal fluid persisted and eventually completely reabsorbed.


Other topically treated cases of attempted cystoid dehydration have also been successful. In one, a macular hole appeared 6 months after silicone oil removal. OCT revealed closure of the hole with treatment by 5 weeks.

In another, a macular hole appeared 8 weeks following primary retinal detachment (RD) repair with pars planum vitrectomy and gas. The macular hole closed after topical treatment by 6 weeks.

Medical treatment seems to be successful only in the smallest holes with extensive cystoid hydration that have no evidence of vitreous traction or epiretinal proliferation, Dr. Gentile said.

Without surgery, tractional forces can keep macular holes from entering phase III and closing, he said.

These tractional forces can either be A-P or tangential from epiretinal proliferation.

A delayed or recurrent pivotal event can occur years after a break in the ILM if tangential traction causes a break in the ELM, Dr. Gentile said.

He gave the examples of a recurrent macular hole that occurred 2 years after successful macular hole closure, and a macular hole that occurred 4 years after RD repair. OCT images revealed increasing epiretinal proliferation just before the macular hole opened.

The pathology of membranes removed during vitrectomy showed significant cellular proliferation, he said.


Immunohistochemistry revealed glial cells positive for smooth muscle actin consistent with contractile elements and tangential traction.

Summarizing, Dr. Gentile said the evaluation of multiple OCT images supports a theory of combined traction and hydration to explain macular holes. (Figure 2)

Morphing video case studies1


  • Gentile RC, Landa G, Pons ME, Eliott D, Rosen RB. Macular hole formation, progression, and surgical repair: Case series of serial optical coherence tomography and time lapse morphing video study. BMC Ophthalmology. 2010,10:24. Accessed Sept. 21, 2015.


Ronald C. Gentile, MD


This article was adapted from Dr. Gentile’s presentation at the 2015 meeting of the American Society of Retina Specialists. Dr. Gentile did not indicate any proprietary interest in the subject matter.

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