**18. Autologous neurosensory retinal transplant (ART)**

In 2016, Grewal and Mahmoud introduced the use of an autologous full-thickness retinal free flap for closure of refractory myopic MHs. They applied endolaser and diathermy in a circular pattern around a 2-disc diameter area of the retina and using a bimanual approach with vertical scissors and forceps obtained a retinal free flap. Instillation of perfluoro-noctane heavy liquid over the flap was followed by a direct PFC-silicone oil exchange [98–102].

#### **19. Human amniotic membrane (hAM) transplantation**

Rizzo [103] describes the use of a human amniotic membrane (hAM) for MH treatment. A 2 mm disk of hAM grasped by forceps under fluid or perfluorocarbon was transplanted into the subretinal space. It is speculated that the hAM stimulates retinal pigment epithelium (RPE) cells division.

Kuriyan [104] described the use of commercially available human amniograft from Bio-Tissue (Tissue Tech, Miami) using sub- and pre-retinal placement. A dermal punch may be used to trim the tissue for hole placement. The chorion side is supposed to face the retinal pigment epithelium. Once in place inside or on top of the MH, the fluid-air exchange was performed.

### **20. Autologous platelet concentrate**

Gaudric [105] explored the effects of autologous platelet concentrate (APC) in macular hole closure by injecting some APC in the hole at the end of a

vitrectomy and obtained an improvement in anatomical closure rate. In a study comparing ILM peeling versus ILM peeling plus platelet-rich plasma (PRP) a significant improvement in anatomic and functional results was reported in eyes that had an application of PRP [106]. Several growth factors and cytokines are released by platelets and platelet-rich plasma has been used in various medical conditions [107]. Autologous PRP has been used in more complex holes such as myopic and refractory MH's with encouraging anatomical and functional results [108]. PRP derived from a patient's peripheral blood requires special tools, which may not be always available. One study found low rates of closure in refractory MHs with autologous blood [109] but a further study found high rates of closure when combining the inverted ILM flap technique with autologous blood for large MHs [110].

#### **21. Subretinal blebs**

The concept underlying this technique is that it is thought to increase retinal compliance by releasing the adhesions of photoreceptors to the retinal pigment epithelium (RPE).

The ILM is peeled in the usual manner at the sites of the injection. A small-gauge subretinal cannula (usually 38-41gauge) is used to inject a small volume of fluid under the retina, and usually few blebs are created by injecting BSS into the subretinal space. A confluent perifoveal serous detachment is induced, using a Tano diamond-dusted scraper or a Flex Loop to help massage the sub-retinal fluid until the retina surrounding the macular hole is detached. A fluid-air exchange is performed, and gas or silicone oil is used. This procedure has been shown to be a viable option for the closure of recurrent or persistent holes [20, 111, 112].

Multiple entry sites into the retina may be avoided as suggested by Felfeli [113] using a silicone extrusion cannula to inject fluid through the macular hole. Once the central retina has been detached by refluxing fluid into the macular hole the margins of the hole are once more re-opposed by carefully massaging them and this is followed by a fluid-air exchange and then gas tamponade. In a series of 39 complex cases, this technique resulted in a 95% closure rate. This procedure is especially useful where chorioretinal scarring is present at the macula resulting in extra adhesion of the retinal layers.

### **22. Retinal relaxing incisions**

Charles [114] reported using retinal relaxing incisions in six eyes to release tangential traction and increase retinal elasticity. This procedure does result in damage to the neuroretina and potentially the underlying RPE and visual improvement were limited to 3 cases.

Reiss [115] described 7 patients treated with five radial full-thickness incisions and gas tamponade. Using this procedure, the investigators reported 100% anatomic success in patients with refractory MH's.

The need to perform a deep incision in the retina with no damage to the underlying retinal pigment epithelium and choroid makes this procedure more technically challenging than others and with potentially greater risk.
