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Role of Human Amniotic Membrane in Surgical Procedure of Re-occurring Macular Holes


Professional research studies are in progress to validate the promising outcomes obtained thus far with subretinal implantation of human amniotic membrane plugs in the treatment of large and recurrent macular holes (MHs).

Macular holes are tears or gaps in the retina’s fovea centralis, and also can be acquired, acute or subacute, spontaneous or traumatic. They can cause serious deterioration of vision, if left unattended and therefore need to be treated.

Recent, novel surgical approaches in the management of MHs offer the possibility to improve visual acuity in people with large and recurrent macular holes that would otherwise be destined to lose vision in the affected eye.

Following a short introduction of MHs, this article provides an update on surgical treatment approaches. The initial description of MHs dates back to Hermann Knapp in 1869, who reported them as resulting from direct blunt ocular trauma.  People with MHs without a history of eye trauma were increasingly observed, as well as by 1970, just 5-10% of them were ascribed to injury, with the rest considered idiopathic. Presently, the large majority of MHs are attributed to vitreomacular traction.

Clinical suspicion is validated by slit-lamp fundoscopic evaluation, which reveals a distinct round or oblong sore in the macula with yellow-white deposits at the base. Optical coherence tomography (OCT) verifies the clinical diagnosis and allows the lesion to be classified into one of Gass’ 4 stages.

Surgical approaches
Ophthalmologists defined the initial modern-day surgical technique to MHs in 1991. This strategy is still used today and also is standard procedure for holes under 400 µm in size.
The procedure consists of the following stages:

  1. A substantial 23- to 27-gauge pars plana vitrectomy;
  2. Then a detachment of the posterior vitreous cortex with internal limiting membrane (ILM)- also called peeling;
  3. Epi-retinal membrane (ERM) peeling around the opening and detailed fluid-gas exchange (gas tamponade);
  4. Followed by postoperative face-down positioning

The preoperative diameter of the MH plays an important role in choosing the very best surgical technique as well as in predicting postoperative closure of the hole as well as visual outcome. It is consequently suggested to take into consideration the requirement to precisely determine the width of each hole with an OCT calliper prior to choosing the surgical strategy. Undoubtedly, for all sorts of vitreoretinal surgical procedures, an excellent preoperative strategy helps to attain the very best outcome.

A study explained the traditional ILM-flap strategy, and it was also consequently changed in 2015, when the temporal inverted-ILM-flap method was introduced. With this technique, following core vitrectomy and also color staining, the ILM is not completely removed from the retina, however it is instead left in position, affixed to the sides of the MH. This ILM remnant is then inverted to cover and fill the MH and allow the natural processes to take place. Finally, fluid-air exchange is performed.

According to one more study, which compared the use of inverted ILM-flap, free-flap and conventional ILM peeling, although all techniques showed a tendency towards visual improvement, the inverted-flap strategy seemed to induce a quicker and also more significant healing in the short term.

From our point of view, despite the the optimal anatomical results, it remains unclear as to how good a substrate the ILM flap is for the remodelling of the neuro-sensitive retina, provided the fibrogenic capacity of the ILM plug and also the uncertainty regarding the role fibrotic proliferation may play in restoring  visual function.

Until recently our surgical approach for large and recurrent recurring MHs was to inject autologous whole blood of the patient into the macular defect: a three-port 23-gauge the pars plana vitrectomy was carried out and the main portion of the retina coloured with indocyanine green. ILM peeling after that took place with the assistance of scraper as well as thumb forceps.

A partial liquid-air exchange followed, as well as the injection of one to two drops of blood.

After aspiration of excessive fluid and blood, the surgery was completed with a low-density silicon oil tamponade.

Anatomical results utilizing this technique were relatively satisfying yet functional ones were controversial.

Remarkably, other eye surgeons contrasted both physiological and functional success when making use of platelet concentrate or whole blood to cause closure of consistent MHs. Their outcomes indicated that the previous technique seemed to provide better outcomes.

In specifically large or recurrent MHs in which the ILM has currently been eliminated throughout previous surgery, transplantation may provide a solution to close the holes. A research published in 2016 reported using the lens capsule in an effort to close MHs, with encouraging outcomes. One more autologous transplant was after that introduced. It included a neurosensory peripheral retinal transplant, followed by tamponade: either silicone oil tamponade, or short-term perfluoro-n-octane heavy liquid tamponade. Anatomical outcomes were good however success in postoperative visual skill was limited.

Making use of amniotic membrane
A novel, much less intrusive option to autologous tissue transplantation in the surgical treatment of large as well as reoccurring MHs is the use of human amniotic membrane (hAM) transplant (or implantation). With this technique, the lens capsule and the peripheral retina of the affected eye are left unbroken. A plug of lyophilised or cryo-preserved hAM is used instead of the patients’ tissue to repair the MH.
Usage of hAM in surgery is not new. Applications of hAM in surgery generally, as well as in surgical ophthalmology particularly, have been assessed. Up until 2018, using hAM in clinical ophthalmology had been restricted to the eye surface.
In one research released in 2018, hAM patches were placed via an intraocular approach to repair large and reoccurring MHs. Interestingly, from a historical perspective, repair work of MHs with hAM had actually already been attempted in the mid-20th century, with a surgically challenging retro-bulbar strategy in 1957 and in 1964.
Animal and vitro experiments preceded existing day clinical use of hAM. Experiments conducted in pigs’ eyes revealed the result of transplanted amniotic membrane on subretinal wound recovery.

Amniotic membrane layer modified choroidal neovascularisation after mechanical damage to Bruch’s membrane and seemed to act as a basement membrane layer alternative to the proliferation of retinal pigment epithelium (RPE). In vitro, it was shown that RPE tissue cultured on hAM had an epithelial phenotype and also produced growth factors essential for retinal homeostasis.
A 2018, prospective, consecutive case-series described positive results when hAM was implanted in 8 patients that had large recurring MHs. All patients had already gone through the pars plana vitrectomy with ILM peeling and also gas tamponade. The hAM was supplied cryopreserved from a human tissue bank as well as was defrosted intraoperatively before insertion.

In all patients, OCT at 1 week postoperatively, revealed MH closure with neurosensory retina overfilling the hAM. Best corrected visual acuity increased from 1.48 ± 0.49 log of the marginal angle of resolution (logMAR), (20/800) preoperatively to 0.71 ± 0.37 logMAR (20/100) 3 months postoperatively, and to 0.48 ± 0.14 logMAR (20/50) 6 months after the procedure. No ophthalmological adverse events were seen throughout follow-up.

In a further study, hAM was used in 10 people with high near-sightedness and MHs associated with retinal detachment who had actually gone through a minimum of one pars plana vitrectomy. Half of the patients got silicon oil and the other half 10% octafluoropropane as tamponade at the end of surgical treatment.

Silicon oil was removed 2 months after surgery. Outcomes were really satisfying since retinal re-attachment was accomplished in all patients and also visual acuity increased from 1.73 logMAR to 0.94 logMAR after 6 months.
It appears that hAM is well tolerated. The possibility of hAM being rejected has actually additionally been considered. In 1999, subretinal implantation of hAM in a rabbit model created no proof of swelling or being rejected.
In the wake of these results, implanting of amniotic membranes was started in patients that had large or persistent MHs. Nevertheless, a few of the steps in our clinical strategy differs from that explained by the aforementioned research study: like them, a 23-gauge access was utilized however unlike their technique, we do not make use of a chandelier, so the technique is not bimanual. The amniotic membrane is taken care of with crocodile forceps.
A partial fluid-air exchange happens, leaving a very little amount of fluid at the foveal level in order to promote the manoeuvre of insertion of the amniotic plug. Implantation of the membrane might be facilitated by the use a Tano scraper. No perfluorocarbon (PFCL) is used. Surgical treatment is completed with liquid-air exchange as well as, finally, washout with perfluoropropane occurs.
The best possible end result, in regards to physiological results as well as visual acuity, is achieved when patients are able to stay in a facedown setting for a number of days. In those who have handicaps or high comorbidities and also who are, for that reason, incapable to hold the facedown setting for a long period of time, silicon oil is utilized to maintain the amniotic membrane in place after insertion.

Concluding thoughts
Professional research studies are currently underway to validate the promising results obtained up until now with subretinal implantation of hAM plugs in the therapy of large and also recurring MHs and results are awaited. It seems that, along with anatomical success, the amniotic membrane stimulates retinal ingrowth and also brings about enhancements in visual acuity, which is positive to say the least.
Therefore, it is assumed, attempts should be made to further the understanding of this novel technique in order to evaluate its capability to bring back visual function. It is recommended that an accurate comparison of preoperative and postoperative determined parameters such as visual field evaluation as well as electroretinogram tests be done, which can confirm this technique.
Finally, it is attested that the implantation of amniotic membrane might provide new hope in bringing back vision in people with an otherwise grim outlook.

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