Author: Ameen Marashi, MD
Documentation of age, duration of visual loss is essential, which includes reduced vision, micropsia, metamorphopsia, scotoma.
Detailed documentation of familial and ocular history such as myopia, ocular inflammation, peripheral retinal break, previous ocular or head trauma, vitrectomy, or cataract extraction surgery to this eye or the fellow eye and if there are a history of sun or eclipse gazing.
Systemic history of a disease or drug intake may induce cystoid macular edema; older females are more prone to develop macular hole than men .
A list of ocular examination should set
1) Best-corrected visual acuity (BCVA) for near and far is an essential step that can be performed by a trained optometrist or certified ophthalmologist to document the visual impairment.
2) A slit-lamp examination done with a thorough exam of clarity and regularity of the cornea and conjunctival abnormality such injection of conjunctival vessels should be documented, and any other inflammations of the conjunctiva or eyelids documented, along with iris exam and crystalline lens exam to rule out cataract or intraocular lens (IOL) to document the position and clarity of the posterior capsule, it integrity wither it ruptured during cataract extraction or YAG laser capsulotomy was done.
3) Anterior hyaloid examination with retro illumination using slit-lamp microscopy to rule out tobacco dust (pigmented cells) and differentiate it from blood and inflammatory cells.
4) Intra Ocular Pressure (IOP) documentation is essential as high IOP may be associated with patients with glaucoma history; Note when high IOP spotted a corrected IOP documented after central corneal thickness measurement
5) Bilateral dilated fundus exam is an essential and detailed examination of the optic disc, macula, posterior pole, a mid-peripheral and peripheral retinal exam with specialized indirect wide-field lenses using slit-lamp biomicroscopy using wide-field lenses and indirect ophthalmoscopy with scleral indentation  to document the following:
Core and posterior cortical of the vitreous searching for pigmented, blood, and inflammatory cells along with the presence of the Weiss ring.
Documenting the extent of posterior vitreous detachment and syneresis if possible.
Posterior pole examination to rule out the presence of vitreomacular traction or epiretinal membrane.
Peripheral and mid-peripheral retinal exam to rule out lattice degeneration, tufts, degenerative schisis, retinal breaks, retinal dialysis, and vascular avulsion.
The Watzke-Allen sign evaluated by shining the slit-lamp on the full-thickness macular hole and make sure the patient sees a break in the slit lamp light confirming a positive test
Retinal exam in case of ocular trauma history should rule out the presence of choroidal rupture, commotio retinae, and retinal hemorrhages.
The macular hole features different patterns depends on stages:
· Yellow spot with loss of foveal depression for stage I a macular hole with no vitreofoveal separation
· Yellow ring for stage I b macular hole with no vitreofoveal separation
· Horseshoe tear or eccentric oval size less than 400 μm in the edge yellow border for stage II macular hole with or without perifoveal opacity (operculum)
· Rounded full-thickness macular hole with elevated rim and size more than 400 μm with perifoveal vitreous detachment but attached vitreous around the optic disc for macular hole stage III with a cuff of intraretinal cysts with or without perifoveal opacity (operculum)
· Rounded full-thickness macular hole with elevated rim and size more than 400 μm with posterior vitreous detachment with the presence of Weiss ring for macular hole stage IV with a cuff of intraretinal cysts.
· The lamellar hole features lobulated or rounded reddish colored thinning in the area of the cyst roof's avulsion without a cuff of intraretinal cysts.
· Drusen-like deposits are sometimes seen at the level of RPE in the macular hole and might be a sign of a chronic hole.
· A gap in ERM may cause a macular pseudohole, which features a rounded or oval reddish central area surrounded by the epiretinal membrane.
Fundus images useful to document the presence and progression of epiretinal membrane and macular hole along with staging, nevertheless fundus images can give a clue of macular hole closure post-surgical treatment.
Optical Coherence Tomography (OCT)
OCT is the most important and sensitive tool to diagnose and stage macular holes and clearly show the pathological findings of vitreous adhesion and anterior-posterior traction. OCT rules out the presence of tangential traction caused by the epiretinal membrane. Hence, OCT is crucial for decision making.
OCT can measure the size of the macular hole accurately and usually the narrowest site in the mid retina between hole edges used for hole size measurements.
Macular hole stages findings on OCT are the following:
Stage 0 OCT shows perifoveal vitreous detachment but with vitreofoveal adhesion, not causing any traction nor disruption of inner retinal tissues.
Stage I a which shows vitreofoveal oblique anterior-posterior traction that contributes to a small disturbance in the inner retinal tissue along with elevation and disruption of interdigitation or/and ellipsoid zone.
Stage I b shows oblique vitreofoveal anterior-posterior traction with the only ILM left with split in the inner and outer retinal tissue 
Stage II shows full-thickness macular hole with partially attached vitreous and operculum which contains retinal tissue however the size of the hole can variable and the edges of the macular hole may contain cystic formation 
Stage III shows full-thickness macular hole with variable size with elevated edges and cystic formation in the macular edges; however, the operculum and foveolar cortical vitreous is completely detached but with attached vitreous at the optic disc.
Stage IV shows a full-thickness macular hole with variable size with elevated edges and cystic formation in the macular edges; however, the operculum and foveolar cortical vitreous are completely detached from the optic disc.
The epiretinal membrane may be presented in stage III and IV more than stage I and II;  however, vitreomacular traction not presented with stage III and IV and presented in stage I and II 
The lamellar hole may present as a partial-thickness defect of the inner retinal tissue with a cleft between the outer plexiform and outer nuclear layer at the level of Henle’s fiber layer  and irregular thinning of the fovea, and it contains cystic formation. However, the outer retinal tissue is intact; sometimes the lamellar hole may be associated with an epiretinal membrane that appears as medium reflectivity, which may not induce any tangential traction. In other cases, it does induce tangential traction, which appears as focal attachments causing inner retinal tissue disruption. Enface OCT can confirm it as retinal folds; nevertheless, Enface OCT may show hyporefelctive area indicating the area of the cleft.
A lamellar hole sometimes shows pseudo operculum, or it can show in some cases vitreous attachment .
OCT is essential to assess the closure of the macula hole post-treatment or follow up, which will show a lack of central interdigitation and ellipsoid zone.  This explains the reduction of vision despite successful closure of the macular hole, and the length of the ellipsoid zone and external limiting membrane correlates after macular hole closure visual acuity. 
Pars Plana Vitrectomy (PPV)
PPV with ILM peeling using a wide-field viewing system and transition to sutureless PPV has shortened the operation time and improved postoperative recovery and results.
PPV offers a high success rate of macular hole closure, even in large macular holes. In combined surgery with cataract removal and intraocular lens (IOL) implantation considered in patients above 60 years old, which will spare the patient future surgical intervention and will allow more gas to fill inside the eye .
The principle of PPV is to induce complete posterior vitreous detachment (PVD) with complete vitreous removal and to stain the ILM and to peel it along with epiretinal membrane (ERM) removal (if presented) then to put gas tamponade then the postoperative head posture.
Preoperatively consideration includes instructing the patient the need for the postoperative head position, especially for large full-thickness macular holes and the ban of air traveling and to examine the retinal periphery to rule out any retinal breaks and to manage it with laser retinopexy preoperatively.
The type of anesthesia depends on surgeon preference as young patients, and complicated cases require general anesthesia, while other simpler cases may be done with local anesthesia and sedation.
When using the trocar system, the available sizes are 23, 25, and 27 gauge the conjunctiva displaced using cotton applicator or conjunctival forceps. The trocar knife is inserted 30 degrees into the sclera then perpendicular to create a self-sealed scleral incision 4.00 mm from the limbus in phakic eyes and 3.5 mm in pseudophakic or aphakic eyes.
The trocar is inserted in the inferior temporal just below the horizontal meridian, and this site is used for infusion cannula. The infusion is turned on before inserting it to release air bubbles, then inserted.
Insertion of infusion in the intravitreal cavity should be inspected under the microscope with an external light source. Care is taken, not to insert the infusion cannula in the suprachoroidal space.
While the other trocars one trocar is inserted in the superior nasal. The trocar is inserted from the lowest point of the nose bridge, and the additional trocar is interested in the superior temporal.
Areas of conjunctival scar or abnormalities should be not used as trocar insertion sites
If a 20 gauge system is used then, conjunctival peritomy is needed and sclerotomies made with MVR blade and the inferior temporal sclerotomy made after placing fixation suture which will fixate the infusion cannula.
The core vitrectomy is initiated, and the core vitreous removed then posterior vitreous detachment (PVD) is provoked if it is not already presented using triamcinolone  which stains the vitreous and helps to complete removal of posterior vitreous, care must be taken not to induce iatrogenic retinal break while inducing PVD .
It is advisable to complete removal of vitreous up to Ora with vitreous base shaving as this will reduce the risk of postoperative retinal break formation due to traction induced by gas tamponade to avoid retinal detachment  along with prolonging gas filling to achieve a better tamponade.
ILM is stained with Brilliant Blue 0.025% (0.25mg/ml) for several seconds , but ILM can be stained with trypan blue as well but after fluid-air exchange  or ICG 0.05 % for less than 30 seconds to avoid RPE toxicity .
The ILM is pinched by ILM end grasping forceps from the temporal of the macula to avoid harming the RNFL in the nasal to the fovea. After flap creation, the ILM is peeled in a circular motion  (macular rhexis), peeling all the ILM up-to the arcades.
A diamond-dusted scraper used to create an ILM flap may damage the underlying RNFL and cause future visual field defects .
In the case of epiretinal membrane presented, it can be stained with trypan blue or negatively stained with Brilliant Blue and easily removed with a backflushed needle or together with ILM peeling, the epiretinal membrane in cases of the macular hole usually fragile.
A peripheral retinal examination with scleral indentation searching for any iatrogenic retinal breaks, which are managed with endo laser photocoagulation with three confluent rows of laser burns where cryopexy can be used in anterior breaks.
During the last ten minutes during fluid air exchange, the nitrous oxides is turned off in general anesthesia to avoid unpredictable post-operative gas expansion.
Fluid-air exchange continues to remove any water from the eye then followed by air gas exchange either by 20% SF6, 16% C2F6, or 14% C3F8.
The rationale to use gas as a tamponade is to insulate liquids from the macular hole to initiate the macular hole healing process, and the bigger the hole is, the longer duration of the tamponade needed .
The down head position should be maintained for 10-14 days or longer for larger holes , but the mean duration for hole closure is three days  ; however, in cases of patients can’t maintain a head position or the need for air travel, a silicone oil used as a tamponade.
All sclerotomies are closed with 8.0 vicryl suture, especially when silicone oil used as tamponade and subconjunctival steroids and antibiotic injection administered.
Cataract one of the most common postoperative complications up to 98%  especially for patients above 60 and can reduce the visual significantly and manages with cataract removal by phacoemulsification and IOL implantation combined with vitrectomy or post vitrectomy
Reopening of the hole if ILM or ERM are not peeled, then a revision of vitrectomy needed to peel ILM and ERM removal. If they already removed the autologous blood serum or inverted ILM flap used to fill the hole  (see below the available techniques for reopening macular hole).
Retinal detachment or/and retinal breaks usually an iatrogenic retinal break that occurs in the inferior retina and may lead to retinal detachment (up to 5% of cases).  This can be avoided easily by managing any existing retinal breaks preoperatively or/and complete vitreous removal and vitreous base shaving to avoid vitreous traction induced by gas and inspecting retinal periphery for retinal breaks and managing them as mentioned above.
Other complications such as low rate of endophthalmitis up to 0.05% and inferotemporal visual field defect due to fluid air exchange
This procedure is aimed to minimize the costs of surgical intervention to close the small full-thickness macular hole in stage II, where there is still vitreomacular traction.
The principle of pneumatic vitreolysis is in office injecting of pure gas to induce posterior vitreous detachment to facilitate macular hole closure then the postoperative head posture.
Presurgical consideration before pneumatic vitreolysis includes:
· Patients cannot maintain head position due to neck or back problems, or patients are not mentally competent, are not candidates for this procedure. It requires a drinking bird head position (face down position with bobbing the head up every 10 min) for ten days.
· Any preexisting retinal breaks and lattice degeneration requires prophylactic laser retinopexy.
· Cases presented with small full-thickness holes and with pre existing vitreofoveal traction (e.g., stage II) without epiretinal membranes are the best candidates.
· In contrast, large macular holes do not feature vitreofoveal traction (e.g., stage III or IV) with or without epiretinal membranes are not a candidate for this procedure.
· All mentioned above should be explained to the patient with details, and the patient should understand that this procedure requires postoperative head posture and that this procedure is prone to failure and may need further surgical intervention or even may induce postoperative retinal detachment.
Usually 0.3 ml of pure C3F8 or 0.5 ml of pure SF6 used in pneumatic vitreolysis, the syringes are filled using a 20 mm filter after evacuating all air from the syringe.
The injection should be carried out in sterile conditions where the injection site is prepared by disinfecting the skin using povidone-iodine 10%.
After installing topical anesthesia, and the conjunctiva disinfected using povidone-iodine 4%. Then placing sterile drape and lid speculum isolating eyelashes, a paracentesis performed first.
Injection site measured with calipers 4 mm from the limbus in phakic patients and 3.5 mm in pseudophakic patients. A 30 gauge half-inch needle is used to inject gas perpendicularly in the uppermost site needle should penetrate only one-third of the needle and inject moderately and briskly. The patient's head is rotated before withdrawing the needle.
In case that fish eggs occurred the gas bubbles will coalesce spontaneously within 24 hours.
The IOP is assessed along with patency of central retinal artery, which should be checked using ophthalmoscopy; if this failed to achieve, then secondary paracentesis is required.
New or missed retinal breaks may be treated with laser photocoagulation if not associated with retinal detachment, as the gas itself may be the cause of new retinal tears. However, cases with new retinal breaks associated with retinal detachment managed with pars plana vitrectomy.
The principle of pharmacological vitreolysis is in office injecting of ocriplasmin to induce posterior vitreous detachment to facilitate macular hole closure to close a small full-thickness macular hole in stage II where there is still vitreomacular traction.
Presurgical consideration before pharmacological vitreolysis includes:
Any preexisting retinal breaks and lattice degeneration requires prophylactic laser retinopexy.
Cases presented with small full-thickness holes and with pre existing vitreofoveal traction (e.g., stage II) without epiretinal membranes are the best candidates.
In contrast, large macular holes do not feature vitreofoveal traction (e.g., stage III or IV) with or without epiretinal membranes are not a candidate for this procedure.
All mentioned above should be explained to the patient with details, and the patient should understand that this procedure is prone to failure and may need further surgical intervention or even may induce postoperative retinal detachment.
Ocriplasmin should be diluted first as it comes in vial 0.5 mg in 0.2 ml and kept freeze then it thawed after that a sterile 0.2 ml of sodium chloride solution 0.9 % is injected in the vial after swapping it with alcohol and then swirled until the solution is clear without any participates then 0.1 ml is withdraw using the 19 gauge needle and then the needle changed to 30 gauge needle for injection of 0.125 mg of ocriplasmin.
The injection should be carried out in sterile conditions where the injection site is prepared by disinfecting the skin using povidone-iodine 10%.
After installing topical anesthesia, and the conjunctiva disinfected using povidone-iodine 4%. Then placing sterile drape and lid speculum isolating eyelashes.
Injection site measured with calipers 4 mm from the limbus in phakic patients and 3.5 mm in pseudophakic or aphakic patients, a 30 gauge half-inch needle is used to inject ocriplasmin 0.125 mg in 0.1ml diluted solutio
New or missed retinal breaks may be treated with laser photocoagulation if not associated with retinal detachment, and ocriplasmin itself may be the cause of new retinal tears. However, cases with new retinal breaks associated with retinal detachment managed with pars plana vitrectomy.
Other complications may occur, such as visual field defect, blue color dyschromatopsia, floaters, photopsia, and weakening of lens zonules and subluxation. 
In case of macular hole stage I a or stage I b (impending macular hole)
-Treatment is not required at this stage; only observation by OCT as 50% of cases  will resolve spontaneously within months.
- If there are no visual symptoms, the patient is followed up bi-monthly on OCT to see if the spontaneous release of the vitreomacular traction without developing a full-thickness macular hole. However, prompt exam is scheduled if the patient developed any new symptoms;  therefore, patients should do self-exam using the Amsler grid.
-Although stage one macular hole usually accompanied by good visual acuity and has an excellent visual prognosis but the worse the vision at baseline, the more likely it will progress to the full-thickness hole. However, if the spontaneous release of the vitreomacular traction, then it is unlikely to develop a macular hole in the future .
In case of idiopathic full-thickness macular hole stage II
- In case of small full-thickness macular hole size, less than 250 μm with perifoveal vitreous traction may close spontaneously in 16% of cases  after spontaneous posterior cortical vitreous detachment the vision may improve, but some eyes will keep on having a defect in visual acuity due to loss of ellipsoid zone .
- Treatment with pneumatic  or pharmacological  vitreolysis is recommended for small full-thickness macular holes within one or two weeks from the diagnosis. Still, the pneumatic vitreolysis is more effective in releasing vitreomacular traction up to 50% to 80%  more than pharmacological vitreolysis, which can release vitreomacular traction up to 24.6%  besides the pneumatic vitreolysis is more cost-effective than the pharmacological vitreolysis.
-In cases of medium (250 μm to 400 μm) and large (more than 400 μm) size full-thickness macular hole PPV indicated  within one month of diagnosis, however large macular hole may benefit from ILM peeling  and postoperative head down positioning .
In case of idiopathic full-thickness macular hole stage III or IV
- PPV with ILM peeling indicated ; however, inverted ILM flap may have a higher macular hole closure success rate in a hole larger than 400-500 μm . Surgery is considered within one month of diagnosis with head down positioning as a large full-thickness macular hole may require a longer period of head-down positioning.
-The patient followed up every one-two days then every one to two weeks with strict head down positioning
In cases of reopening of macular hole
-In case of reopening of the macular hole, a revision of vitrectomy is done and ILM peeling with ERM removal if not done already.
-In case of reopening of the macular hole in light of peeled ILM and no ERM then an inverted ILM flap filling the hole  , autologous blood  , autologous retinal graft  especially in cases of refractory macular hole in myopic patients or amniotic membrane.
Other cases of macular hole
- The lamellar hole usually remains stable over time; however, in cases that lamellar hole causing a progressive decline in visual acuity, especially when associated with an increase of lamellar hole diameter with thinning of the fovea based on OCT with tangential traction caused by ERM. PPV combined with cataract extraction and IOL implantation with ERM removal, and ILM peeling may improve visual acuity. Still, at the same time, it may cause the progression of a lamellar hole to a full-thickness macular hole, which needs surgical intervention .
- The traumatic macular hole usually due to anterior-posterior compression of the globe or due to Berlin edema closes spontaneously and improves vision up to two lines within six weeks if it didn’t close spontaneously then PPV with ILM peeling indicated. However, the inverted ILM flap filling the hole may be considered, but the outcome of the surgery is poorer than the idiopathic full-thickness macular hole. 
- The other eye had a full-thickness macular hole, a close monitor with OCT to the macula, especially if there is vitreomacular adhesion or traction; however, if there is PVD, it is unlikely to develop a full-thickness macular hole in the future.
Flow chart summarizes the approach and management of macular hole
Follow up & prognosis
- Follow up should include BCVA, IOP, and fundus exam, where OCT used to assess macular anatomy post-surgery.
- The success rate to close the full-thickness macular hole is up to 90 to 95% ; however, visual acuity is governed by the size and duration of the hole which compromises the status and length of the ellipsoid zone and interdigitation zone as visual improvement is between 20/200 to 20/40 and about 58% can achieve visual acuity 20/40 and more , the used dye to stain the ILM may influence post-surgical visual acuity as ICG have a lower postoperative visual acuity than Brilliant Blue .
- Head down positioning mandatory for 10 to 14 days, although larger holes may need a longer duration of head-down position; a smaller hole may not need head positioning .
-Patients are followed up within one to two days post-surgery, then every one to two weeks then depends on the surgical outcome, which is assessed by OCT.
- The patient should be instructed not air travel nor to climb high altitude as it might trigger unpredictable gas expansion and induce increased intraocular pressure and cause damage to the optic nerve.
- Patients who required additional surgery due to refractory cases will suffer from reduction to 20/200 of vision up to 70% of cases; however, cases in which hole reopened again may have a better visual prognosis .
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49. Baumann, Carmen MD, FEBO; Kaye, Stephen BSc, MBBch, FRCS, FRCOphth, MD; Iannetta, Danilo MD; Sultan, Ziyaad BSc, MBBS, FRCOphth; Dwivedi, Rahul Bsc(Hons), MBChB, FRCOphth; Pearce, Ian MBChB, BSc, FRCOphth EFFECT OF INVERTED INTERNAL LIMITING MEMBRANE FLAP ON CLOSURE RATE, POSTOPERATIVE VISUAL ACUITY, AND RESTORATION OF OUTER RETINAL LAYERS IN PRIMARY IDIOPATHIC MACULAR HOLE SURGERY, Retina: October 2020 - Volume 40 - Issue 10 - p 1955-1963doi: 10.1097/IAE.0000000000002707
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These guidelines were reviewed and updated in October 2020