Animal studies

Machemer and Steinhorst utilized a rabbit model to demonstrate the feasibility of purposeful retinal detachment with subretinal infusion via a transscleral approach.² Electron microscopy confirmed preservation of photoreceptor nuclei and mitochondria in the inner segments with some disruption of the outer segments, suggesting this technique was reasonably atraumatic and may be well tolerated. In addition, successful retinal translocation around the axis of the optic nerve following 360° peripheral retinectomy was also demonstrated. Reattachment of the retina resulted in retinal folds due to the rigidity of the medullary wings. Additionally, maximal shaving of the vitreous base was found to be critical for creation of the retinectomy. Residual vitreous resulted in increased difficulty and less predictability during creation of the retinectomy.²

The rabbit model has also been used to demonstrate the utility of calcium- and magnesium-free infusate in reducing retinal adhesion without creating cellular toxicity.^3,4 Collateral damage to photoreceptor outer segments was also reduced by using calcium- and magnesium-free solutions. Temporary electroretinogram (ERG) depression of b-wave amplitude was noted on postoperative day 1, but this was transient.³ Animal studies have also revealed that dark adaptation results in easier retinal detachment with reduced retinal damage. In model surgery, a red-free intraocular light source was used during the surgical procedure to prevent reversal of dark adaptation.⁴

Historical perspective and evolution of technique

In 1983, Lindsey first proposed translocation of the retina.⁵ Tiedeman et al. published their proposal for retinal translocation in 1985.⁶ Machemer published the first human surgical cases in 1993. All three subjects had AMD and were treated with 360° peripheral retinectomy and translocation (MTS360, MT360).⁷ The original MTS360 technique involved pars plana vitrectomy with transscleral injection of subretinal fluid with 360° retinectomy, removal of subretinal blood and choroidal neovascularization (CNV); partial fill with silicone oil; retinal translocation; complete silicone oil fill, and finally laser retinopexy. All surgeries were performed under general anesthesia. One of the original patients had significant improvement in central acuity (1/200–20/80).⁷

The original procedure has gone through multiple evolutionary iterations with major developments by Eckardt et al., Toth and Freedman, and Tano.^8–10 Changes to technique have focused on facilitating retinal detachment, effectively translocating the macula, reducing complications (e.g., proliferative vitreoretinopathy, PVR), and decreasing the duration of surgery.^8–18 Because retinal rotation results in significant cyclotorsion,^{8,9,12,14,17,19} extraocular muscle surgery to counter-rotate the globe is used routinely to manage the cyclotropia.⁸ Attempts at reducing the extent of the retinectomy (e.g., <360°) have not been widely adopted due to very high rates of PVR.^10,11,20,21

Variations on MTS360 also included the development of limited macular translocation (LMT) which shifted the macula a shorter distance than with MTS360. De Juan developed a technique to shorten the sclera following detachment of the superotemporal retina across the macula. This resulted in redundant retina that allowed the foveal center to be relocated downward by gravity after surgery, by positioning the patient upright with a partially gas-filled eye. Because of the variable and limited distance of macular displacement, this procedure has decreased in use.^22–24

Macular translocation has been used to describe all of these surgical displacement procedures. The terms retinal rotation, full macular translocation, macular translocation surgery with 360° peripheral retinectomy, MTS360, and MT360 have been used to describe the Machemer technique. Limited macular translocation or macular translocation with scleral “infolding” or “exfolding” are terms that have been used for the partial retinal detachment, de Juan technique and its subsequent modifications.

Indications

Although clear guidelines for the indications for macular translocation are not established, there are several generally agreed upon principles. Anti-VEGF (vascular endothelial growth factor) therapy is clearly the first-line treatment for subfoveal neovascular disease.^31,32 MTS360 surgery is only considered in patients with bilateral central vision loss due to the postoperative torsional diplopia. The surgical eye is typically the eye with better visual potential, more recent vision loss and greater preservation of retinal architecture. It may be considered in nonresponders to anti-VEGF treatment, eyes with extensive subretinal fibrosis, or some cases of massive subretinal hemorrhage, retinal pigment epithelial tears or submacular diseases that are not VEGF-driven.^{8,9,12,15,17,26,33–39} Although macular translocation has been reported in numerous diseases including neovascular AMD, non-neovascular AMD with geographic atrophy, myopic degeneration with CNV, ocular histoplasmosis with CNV, adult-onset foveomacular vitelliform dystrophy, punctate inner choroidopathy with subfoveal CNV, angioid streaks with CNV, North Carolina macular dystrophy, and central serous chorioretinopathy, there are cases where it has a lower likelihood of success.^{8,9,12,15,17,26,33,36–39} In cases of central geographic atrophy with AMD, the atrophy has often recurred in the new foveal location, and many would consider this a contraindication to surgery. Underlying ocular inflammatory diagnoses (e.g., punctate inner choroidopathy, ocular histoplasmosis) may also be associated with worse outcome.³³ General inclusion and exclusion criteria for patients being assessed for MTS360 are outlined in Table 120.1.

Table 120.1 Inclusion and exclusion criteria for macular translocation with 360° peripheral retinectomy

^* Duration of vision loss determined by patients’ reports of when they were unable to perform vision-related daily activities such as reading and driving.

History and retinal examination

A thorough retinal examination is critical prior to performing macular translocation surgery. A peripheral retinal examination with scleral depression is important to identify peripheral pathology that may pose issues during the procedure (e.g., peripheral holes, chorioretinal scars that may inhibit retinal detachment). The lens status of the patient is also important. Phakic patients typically undergo phacoemulsification and posterior chamber lens placement prior to or at the time of macular translocation surgery. If the patient is pseudophakic, the type of intraocular lens and the status of the posterior capsule are important given the planned infusion of silicone oil. Other critical components of the ocular history include previous strabismus surgery or previous vitreoretinal procedures. The longer the duration of vision loss, the greater the likelihood of atrophy or scarring of the neurosensory retina with permanent dysfunction. Unfortunately, the duration of significant vision loss is often difficult to ascertain.

Diagnostic testing

Preoperative evaluation for macular translocation may include fundus photography, fluorescein angiography, optical coherence tomography, fundus autofluorescence, fixation, and microperimetry. These tests may be useful to identify eyes that are poor candidates for MTS360 such as eyes with severe macular chorioretinal scarring, extensive neurosensory retinal atrophy, widespread RPE atrophy, CNV in the site of proposed translocation, retinal angiomatous lesions, chorioretinal anastomoses, or unexpected retinal vascular disease. Unfortunately, overall these tests, including fixation and microperimetry have been shown to be poor predictors of 1 year visual outcomes in patients who were considered eligible for MTS360.⁴⁰

Optical coherence tomography (OCT) has revolutionized the diagnosis and management of numerous vitreoretinal diseases. The high-resolution view of the ultrastructure of the retina with spectral domain can be helpful in identifying outer retinal atrophy which may limit the utility of macular translocation. Histological evidence has shown significant photoreceptor atrophy overlying disciform scars.⁴¹ If outer retinal atrophy is present in the macula on OCT, patients are probably unlikely to realize improvement in visual function after macular translocation. Surprisingly, retinal thinning on time domain OCT before surgery was associated with good visual outcomes in one study.⁴⁰ However, time domain OCT lacks the resolution of SDOCT imaging, therefore resolution was not sufficient to identify photoreceptor layer details. In some cases, perhaps the more compact retina was healthier than the edematous retina before MTS360. Additionally, OCT may be helpful in identifying other structural abnormalities that are important to preoperative planning (e.g., large intraretinal cysts, areas of adhesion).

Fluorescein and/or indocyanine green angiography are utilized to assess the extent, location, and activity of the CNV and/or submacular disease process. Additionally, preoperative fluorescein angiography can be helpful in identifying retinal angiomatous proliferation or chorioretinal anastomosis, which should be considered in surgical planning, as these can result in a retinal tear or significant intraoperative hemorrhage during the separation of the retina from the RPE and choroid.^42,43 Additionally, the RPE integrity and perfusion status of the choroid and retina can be assessed. Fundus autofluorescence can also be useful for evaluation of the RPE health of the future subfoveal RPE bed. Hyper- or hypofluorescence in the area of the future foveal location should be considered before committing to surgery.

MTS360

If a patient is phakic, cataract extraction and intraocular lens placement are performed simultaneously at the time of macular translocation. Complete pars plana vitrectomy with elevation of the posterior hyaloid, if attached, is the first step of MTS360. Careful, close shaving of the vitreous base with the vitreous cutter and 360° of scleral depression is performed. Retinal detachment is induced with subretinal fluid injection through a retinotomy that is typically located peripherally within the vitreous base. Posterior retinotomies have been associated with greater epiretinal membrane formation (Fig. 120.2A). A specialized cannula is utilized to infuse the subretinal fluid.^8–11,14,15 A very small retinotomy is made inferonasally with the vitreous cutter at the ora serrata. The retinotomy is marked using endodiathermy. In order to limit back flow, a silicone-tipped cannula larger than the retinotomy is used to infuse subretinal fluid to detach the retina.⁹ If progression of retinal detachment does not occur, a fluid–air exchange is performed which facilitates subretinal fluid displacement from areas of detached retina to areas of attached retina. Although animal models have shown that calcium- and magnesium-free solutions may facilitate retinal detachment, prolonged use of these solutions in humans may result in higher postoperative keratopathy and the use of these solutions is not common.

Fig. 120.2 Diagrams showing the steps involved in macular translocation with 360° peripheral retinectomy. (A) The retina is detached by subretinal injection of fluid through a retinotomy that may be located posteriorly or peripherally. (B) After the retina is totally detached it is then cut at the ora serrata using the vitreous cutter (retinectomy) or retinal scissors (retinotomy). (C) When the retina has been completely cut free at the ora serrata it is reflected and the subretinal lesion is removed. (D) The neurosensory retina is then translocated off the subfoveal abnormality usually in a superior direction. While a number of instruments can be used to manipulate the retina, a modified diamond-dusted silicone-tipped needle that is connected via short tubing to a syringe containing perfluorocarbon is shown here. (E) At completion of the surgery the retina is typically rotated 40–45° displacing the fovea (X) off the bed of choroidal neovascularization (dotted line).

Once the retina is totally detached, the retina is cut at the ora serrata with the vitreous cutter (peripheral retinectomy)^9–11 or retinal scissors (peripheral retinotomy) (Fig. 120.2B).^8,10,11,15 Perfluorocarbon liquid (PFCL) is utilized over the posterior pole of the retina to stabilize the retina while performing the peripheral retinectomy. Once the retina is completely free from the ora serrata, the PFC is removed and the retina is reflected allowing removal of the subfoveal lesion, if present (Fig. 120.2C). The retina is then translocated into the new position. Most commonly, the retina is translocated superiorly (Fig. 120.2D). A small bubble of preretinal PFCL is utilized to stabilize the retina while the translocation is performed. Multiple instruments have been utilized for the retinal manipulation during translocation including retinal forceps^8,10,11 and a silicone-tipped needle,¹⁴ although the diamond-dusted silicone-tipped needle is excellent for atraumatically snagging the retinal surface with very gentle pressure over an arcade, and then sliding the retina. The tip may be connected to a syringe containing perfluorocarbon liquid.⁹ Once appropriate displacement has been achieved (typically approximately 45° off the CNV bed, which equates to the center of the old CNV bed under the inferotemporal arcade), additional PFCL is added to reattach the retina in the manner of a giant retinal tear. Laser photocoagulation is then applied to the retinectomy margins under PFCL tamponade. A direct PFCL/silicone oil exchange is performed to avoid retinal slippage (Fig. 120.2E).

Limited macular translocation

Rectus traction sutures are placed prior to vitrectomy under the lateral rectus and superior or inferior rectus muscles, depending on the planned location of translocation. Five to six horizontal mattress sutures, often 5–0 nylon, are preplaced before inducing a retinal detachment. The sutures are located along the equator, extending for 150–160°, centered in the superotemporal (or rarely inferotemporal quadrant as superior translocation is much more difficult to achieve) (Fig. 120.3). If inferior translocation is needed, the superotemporal quadrant is shortened by placing one suture nasal to the superior rectus, one suture inferior to the lateral rectus, and 3–4 sutures in the superotemporal quadrant. The sutures are left untied until after creation of the retinal detachment. Although this technique creates chorioscleral infolding, other techniques including chorioscleral outpouching have also been reported.^44–46

Fig. 120.3 Scleral sutures are preplaced in a horizontal mattress fashion before retinal detachment. The sutures are held with serrefines until later in the procedure, when they are tightly knotted to shorten the sclera. SRM, superior rectus muscle; LRM, lateral rectus muscle.

After placement of the sutures, pars plana vitrectomy is performed with elevation of the posterior hyaloid. A specialized infusion cannula is used to create focal retinotomies to allow for subretinal fluid injection. As the subtotal detachment progression, an air–fluid exchange can be used to facilitate confluent temporal retinal detachment. The detachment must extend peripherally beyond the imbrication sutures and to the temporal aspect of the optic nerve and including the macula. Following creation of the temporal retinal detachment, the infusion is stopped and a trocar plug is removed to reduce the pressure to near zero. The preplaced sutures are then tightened. After tightening the sutures, a partial air–fluid exchange is performed (i.e., 75–90%). The patient is positioned upright after surgery to achieve the downward foveal displacement.

Positioning

Positioning following MTS360 is based on the surgeon’s preferences. Approaches include face-down positioning or alternating side-to-side positioning thought to diminish pooling of factors for PVR in aqueous medium at the 6 o’clock position. With LMT, the patient is brought to an upright position (Fig. 120.4) for 24 hours to facilitate inferior translocation.

Fig. 120.4 With the upright position postoperatively, the air buoyancy supports the superior retina while the subretinal fluid is accumulated inferiorly, dragging the fovea downward relative to the underlying choroidal neovascularization lesion.

(Adapted with permission from Au Eong KG, Pieramici DJ, Fujii GY, et al. Limited macular translocation. In: Lim IJ, ed. Age-related macular degeneration. New York: Marcel Dekker; 2002.)

Laser treatment

Following both MTS360 and LMT, the previous subfoveal CNV is likely extrafoveal in location (if it has not been removed intraoperatively). If the CNV is active, laser photocoagulation or photodynamic therapy is performed to reduce the risk of CNV growth into the new foveal location and to reduce the risk of further vision loss from hemorrhage. Anti-VEGF therapy may also be considered separately or in combination with other treatment.

Extraocular muscle surgery following macular translocation

Given the extensive translocation that occurs during MTS360, often 30–45° in an upward direction, the amount of torsion exceeds the maximum amplitude of cyclofusion (typically around 15°).⁴⁷ Translocation results in both horizontal and vertical strabismus. In order to alleviate the symptoms associated with excess cyclotorsion, extraocular muscle surgery is performed to strengthen the inferior oblique and weaken the superior oblique. Rectus muscle transposition is also often performed to increase excyclorotation.^8,47 Two major techniques have been described. In contrast to MTS360, LMT does not typically require extraocular muscle surgery due to the limited magnitude of translocation.

The Freedman technique involves performing the extraocular muscle surgery 8 weeks after the MTS360 procedure. Because of separate and thus shorter procedures, general anesthesia is not needed for the extraocular muscle surgery or the MTS360. The post-translocation amount of torsion determines the number of operated muscles. The inferior oblique is advanced to the temporal border of the superior rectus muscle with the anterior and posterior edges 13 and 15 mm posterior to the limbus, respectively, and a complete superior oblique tenotomy is performed. If an eye has between 20 and 35° of torsion, superior transposition of the lateral rectus muscle is also performed adjacent to the superior rectus, 7 mm from the limbus (Fig. 120.5). For the majority of cases, more than 35° of torsion is present and thus the medial rectus is also transposed to the nasal edge of the inferior rectus muscle.⁴⁷

Fig. 120.5 Drawing of torsional muscle surgery to create an excyclotropia in the right eye using the Eckardt technique. (A) The anterior part of the inferior oblique muscle is advanced 12 mm and the posterior part, 9 mm, while the anterior and posterior parts of the superior oblique muscles are recessed the same distances. In addition, muscle strips from two opposing rectus muscles are passed beneath the original muscles and transposed in a clockwise direction and attached at the insertion of the adjoining rectus muscles. (B) If more counter-rotation of the eye is required opposing strips from all four rectus muscles can be moved after the oblique muscle surgery previously described.

Simultaneous extraocular muscle surgery is performed during the initial MTS360 procedure when using the Eckardt technique.⁸ General anesthesia is typically utilized during the combined procedure. Strengthening of the inferior oblique is achieved by advancement or through a 12-mm tuck. The superior oblique is weakened by recession or tenotomy. Each rectus muscle is split by about one-quarter of the width of the entire muscle for a radial length of 15–17 mm. Each strip is passed under the remaining portion of the rectus, transposing them clockwise (right eye) or counter-clockwise (left eye) to the margins of the adjacent rectus muscle (windmill technique) producing excyclorotation (Fig. 120.6).⁸

Fig. 120.6 Drawing of torsional muscle surgery to create an excyclotropia in the right eye from the surgeon’s view superiorly, using the Freedman technique. (A) The first step is advancement of the inferior oblique muscle. Pen marks on the limbus denote the 6 and 12 o’clock positions of the eye, made prior to beginning strabismus surgery. A muscle hook has been placed beneath the superior rectus insertion. The superior oblique tendon has been transected (not shown). The medial and lateral rectus muscles have each been secured on a 6–0 Vicryl suture and detached from their respective insertions on the globe. The inferior oblique muscle, located on a clamp, is being advanced towards the site on the sclera where partial-thickness scleral bites have been taken with the same 5–0 Dacron suture, which is attached to the inferior oblique behind the clamp. (B) The final positions of the medial and lateral rectus and inferior oblique muscles during strabismus surgery are shown. The lateral rectus muscle has been reattached adjacent to the lateral border of the superior rectus muscle. The inferior oblique muscle, having been advanced as shown previously is just visible in the superior temporal fornix. The medial rectus muscle has been reattached adjacent to the medial border of the inferior rectus muscle. The pen markings at the limbus demonstrate the excyclorotation of the globe, which has been effected by the strabismus.

Neovascular AMD

Multiple reports have documented functional outcomes after MTS360 for neovascular AMD (Table 120.2).^{8–12,14–18,48–50} In addition, there has been a prospective randomized clinical trial of MTS360 versus photodynamic therapy with follow-up through 2 years. In that study, MTS360 produced superior vision recovery when compared with photodynamic therapy at both 1 and 2 years, with a gain in near acuity of 7 letters after MTS360 versus loss of 9.6 letters in the PDT group, and a gain of 0.3 letters in distance acuity after MTS360 versus loss of 12.6 letters in the PDT group.^49,51 The subsequent success of antivascular endothelial growth factor inhibitors in the treatment of choroidal neovascularization (CNV) has diminished the need for macular translocation surgery and changed the context of these analyses.^31,32

There have been several reviews of the data from clinical series after MTS360 that show benefit of treatment and document the potential complications of this surgery.8–12,14–18^,48,49,52 Duration of follow-up ranged from 9.6 months to 38 months. Mean preoperative visual acuity ranged from 20/125 to 20/260. Mean postoperative visual acuity ranged from 20/80 to 20/260 and some patients achieved a distance visual acuity of 20/40 or better. The percentage of patients with postoperative improvement in distance visual acuity has ranged from 43% to 66%.^8,15,18,48 Gains in visual acuity of three lines or more ranged from 13% to 36%, while the percentage of patients in each study who lost three or more lines of visual acuity after MTS360 ranged from 6.6% to 56.2% (Fig. 120.7).^{8–12,14–18,48,49}

Fig. 120.7 Color fundus photograph, fluorescein angiogram, fundus autofluorescence, and spectral domain optical coherence tomography (from left to right) documenting macular translocation with 360° retinectomy (MTS360). (A) One month before MTS360 with visual acuity of 20/100, active choroidal neovascularization (CNV), diffuse cystoid macular edema (CME), and atrophy of the retinal pigment epithelium; (B) postoperative year 1 after MT360 with recurrent neovascularization at the edge of the old CNV lesion and CME in the translocated fovea; (C) postoperative year 3 after MT360 with improving visual acuity of 20/80 and regression of CNV and CME after laser and intravitreal antiangiogenic therapy.

MTS360 has also been utilized following photodynamic therapy (PDT) and other non-surgical treatments. Prior to the anti-VEGF era, eyes treated with a single prior PDT session improved after MTS360 from mean visual acuity of 20/160 to postoperative mean acuity of 20/100, while eyes with more than one previous PDT session generally worsened from 20/200 before MTS360 to a mean postoperative visual acuity of 20/250.⁵³ In the anti-VEGF era, a study of 43 patients with anti-VEGF therapy or PDT or both, sustained significant improvement in all measures of visual function at 1 year after MTS360 (mean gain of >9 letters).⁴⁰ An additional study examined 38 consecutive patients in the anti-VEGF era and showed that MTS360 resulted in improved visual acuity, particular in those patients with submacular hemorrhage and CNV, secondary to pathologic myopia.^54,55

Numerous studies have also reported changes in near visual acuity, with near acuity sometimes improving greater than distance acuity.^13,18,49,51 Reported mean preoperative near visual acuity ranged from 20/100 to 20/160, with a significant improvement in mean near visual acuity to 20/63 and 20/55, postoperatively.^8,18 MTS360 has been shown to have better improvement in near visual acuity when compared to PDT (+7 letters versus −9.6 letters).⁵⁶ In several studies, over 20% of patients achieved postoperative near visual acuity 20/40 or better.^8,18,40,57

The impact of MTS360 on other visual functions, including reading speed, contrast sensitivity, and color vision, have also been reported. Significant improvements in reading speed have been found following MTS360 with a mean increase of 26–45 words/minute.^18,40,57,58 MTS360 has been shown to not only improve reading speed and fixation quality, but also to improve saccades during reading activities.⁵⁹ Improved contrast sensitivity has also been documented following MTS360, while color vision has been minimally affected following MTS360.^40,58

Goldman perimetry studies have shown peripheral field loss but overall good preservation of the visual field following MTS360.⁶⁰ Microperimetry studies have shown recovery of central visual sensitivity following MTS360 (Fig. 120.8)^40,59,61 and a new focal scotoma in the superotemporal field due to the translocated CNV bed.⁶¹ Reduction in photopic and scotopic electroretinograms have been documented following MTS360 for up to 5 months after surgery. The mechanism for ERG reduction is not clear, but may be related to length of surgery, composition of subretinal infusate, and duration of detachment.^62–64 In addition to ERG, electro-oculogram findings have shown a decreased dark trough following MTS360, although the Arden ratio was within normal limits.⁶⁵

Fig. 120.8 Fundus photographs with superimposed microperimetry (Nidek MP-1) of the left eye of a 76-year-old female with bilateral AMD who had a 4-month history of progressive vision loss in her second affected eye. Photodynamic therapy with Visudyne had been performed 3 months before for predominantly classic subfoveal neovascularization. Microperimetry was performed using a Goldmann III equivalent target and 4–2 threshold testing strategy. Zero (0) signifies the highest-intensity stimulus and 16 the lowest. An open square equals no response; a filled square equals response to stimulus. (A) Preoperatively best corrected visual acuity on ETDRS testing was 20/250. Microperimetry showed a central dense scotoma with no response to the brightest stimulus centrally, unstable fixation (inset) and a good response to peripherally stimuli. (B) At 1 year postoperatively, best corrected distance visual acuity on ETDRS testing was 20/64 with resolution of central scotoma, stable fixation (inset) and development of a new peripheral scotoma over the displaced choroidal neovascular membrane bed.

Vision-related quality of life (QOL) has been found to significantly reduce in patients with bilateral severe AMD.⁶⁶ Following MTS360, vision-related QOL has been reported to have significant improvement particularly in relation to distance acuity, near acuity, and reading speed. Near acuity was found to have the greatest impact in vision-related QOL. A one line change in near acuity resulted in a 13.7 point change in QOL score, compared with a 1.4–2.1 point change for a one line change in distance acuity or an increase in reading speed of 15 words/minute.⁶⁶ Vision-related QOL showed significant improvement in vision-related subscores following MTS360 in a prospective randomized study.⁵⁶ MTS360 showed significantly higher improvement in QOL scores for general vision, mental health, and dependency compared with treatment with PDT.⁵⁶

Regarding LMT, one study reported that 48% of patients at 6 months gained two or more lines of visual acuity and at 1 year, 40% of patients had gained two or more lines. A total of 31% of patients lost two or more lines of visual acuity.^67,68

Non-neovascular AMD

Macular translocation has also been utilized in geographic atrophy (GA) secondary to AMD. Multiple reports have discussed the use of macular translocation for GA.^36,37,69,70 The first study published included eight eyes undergoing MTS360. Five of eight eyes had visual improvement, one remained stable and two eyes had worsening visual acuity.³⁶ A more recent study included four eyes with GA, and in this study, the mean preoperative and postoperative visual acuity were unchanged.⁶⁹ Recurrent RPE atrophy is a significant concern in patients treated with macular translocation and GA secondary to AMD.^36,69,70

Non-AMD diagnoses

In addition to AMD, multiple other submacular diseases can result in bilateral vision loss. In cases of severe functional limitation, consideration may be given to macular translocation when other treatment modalities are not effective or a viable option (e.g., anti-VEGF therapy, photodynamic therapy, focal laser photocoagulation). Some of these conditions may not be VEGF-driven and may not respond to intravitreal therapy. Although limited in number, macular translocation has been utilized in many of these non-AMD conditions.³³ One recent study examined 16 subjects treated with MTS360 for conditions other than AMD. Conditions included in this study were adult-onset foveomacular vitelliform dystrophy (AOFVD), myopic degeneration, ocular histoplasmosis, punctate inner choroidopathy (PIC), Best disease, angioid streaks, North Carolina macular dystrophy, and central serous.³³ Of all of these conditions, myopic degeneration has been the most widely studied for macular translocation. A large study of MTS360 for myopic degeneration included 52 eyes with a final visual acuity of 20/40 or better in 39% of subjects.⁷¹ In general, eyes with myopic degeneration had smaller CNVs (e.g., 0.4–1.2 disc diameters) and required less retinal rotation than eyes with neovascular AMD. A study of 15 eyes undergoing MTS360 for myopic degeneration reported that 73% of eyes showed visual improvement, with only 10% of eyes losing vision.^16,38,57 A smaller series of three eyes with myopic degeneration, showed a final visual acuity of 20/60 or better in 3/3 eyes, with 2/3 eyes improving ≥3 lines.³³ LMT has also been utilized for treatment of myopic degeneration. A study of 11 eyes undergoing LMT revealed that 64% of eyes achieved a final visual acuity of 20/100 or better.⁷² Another study comparing LMT to submacular surgery and CNV removal in myopic degeneration reported a statistically significant greater improvement in visual acuity following LMT (+3.8 versus −0.07 lines), although these reports were prior to the anti-VEGF era.⁷³

A case study of MTS360 for idiopathic CNV reported worsening visual acuity from 20/63 preoperatively, to 20/100 postoperatively.¹⁶ Comparing inflammatory preoperative diagnoses (e.g., presumed ocular histoplasmosis syndrome (POHS), PIC), with noninflammatory diagnoses (e.g., myopic degeneration, AOFVD, Best disease, North Carolina macular dystrophy, angioid streaks, and central serous), only 20% of eyes with a preoperative inflammatory diagnosis maintained a visual acuity of 20/100 or better, and the mean final visual acuity in those eyes was 20/209.³³ Three of five (60%) eyes with inflammatory disease lost ≤3 lines of visual acuity, and the mean line change in visual acuity was a loss of 1.4 lines.³³ In eyes with a noninflammatory diagnosis the mean final visual acuity was 20/83 with 73% of eyes maintaining a final visual acuity of ≥20/100. Five of 11 eyes maintained a final visual acuity of ≥20/50. The mean line change was +1.0 lines.³³ Though this study was retrospective and small, this suggests that increased caution should be used prior to proceeding with MTS360 for inflammatory diagnoses. The most likely cause of worsening final visual acuity appeared to be an increase in postoperative complications for this group.³³ Polypoidal choroidal vasculopathy (PCV) has also been treated with MTS360, with two reported cases showed visual improvement following MTS360.³⁹

Retinal and RPE changes after macular translocation

The positioning of the previously dysfunctional macula over new underlying RPE provides a unique site to study the relationship between photoreceptor and RPE function in humans with macular disease. The status of these tissues has been examined through numerous imaging techniques after MTS360. This has included: angiography, autofluorescence imaging, spectral domain optical coherence tomography, and color fundus photography.

A striking finding in patients with GA treated with macular translocation is the recurrence of the RPE atrophy in the new foveal bed which has now been reported in multiple studies.^36,69,70 In one study, recurrent RPE changes were seen in 75% of eyes treated with MTS360.⁶⁹ Similar findings of new RPE atrophy are quite rare in patients with neovascular AMD treated with MTS360.⁶⁹ The precipitating factor for RPE atrophy is not clear. Given the rarity of similar findings in MTS360 for neovascular AMD, surgical trauma seems to be an unlikely cause. RPE atrophy may be the primary event, particularly if the increased metabolic activity of the overlying foveal photoreceptors results in increased stress to the fragile RPE. Alternatively, apoptotic photoreceptors may result in secondary RPE atrophy in the new foveal bed. Additional research is needed to further elucidate the mechanisms involved in this phenomenon.

The reports of recurrence of GA were in the era before more routine autofluorescence imaging. The fundus autofluorescence techniques are useful to monitor the health of the new RPE under the macula. In patients with neovascular AMD and with non-AMD diseases such as myopia, the RPE under the new macula demonstrates hyperautofluorescence that persists with little change over months to years.⁷⁷ This finding is often compatible with good visual acuity but may represent stress of densely packed photoreceptors over non-foveal RPE. In addition, the RPE that was in the shadow of retinal vessels for the lifetime of the patient and is now exposed for imaging after translocation, shows decreased autofluorescence relative to adjacent RPE.⁷⁸

Both angiography and OCT imaging are used to monitor for evidence of recurrent CNV, while OCT imaging is also useful to evaluate the photoreceptor layer in the macula after translocation. OCT imaging is also useful for assessment of postoperative cystoid macular edema which may be chronic and responsive to anti-VEGF therapy or antiinflammatory therapy including to intravitreal steroids.

Unintentional macular translocation following retinal detachment repair

Translocation of the macula is a feared complication during retinal detachment repair. Shifting of the retina during surgical repair may occur during multiple time points. Intraoperatively, as the retina is reattached (e.g., during perfluorocarbon liquid infusion, air–fluid exchange), there is some risk of shift. However, postoperative positioning is the most likely source for translocation. Residual subretinal fluid combined with gravitational forces may shift the retina inferiorly (when the patient is upright) or nasally (when the patient is positioned with the nasal side of the surgical eye down). When the detachment involves the superior retina through the macula, this retinal shift can be similar to a limited macular translocation surgery and can result in a retinal fold. The location of the fold would depend on the location of the inferior border of the detached retina.

In one recent study, patients with gas-filled eyes after vitrectomy for retinal reattachment were positioned upright for several minutes prior to face-down positioning.⁷⁸ This upright positioning was carried out to determine if subtle shifts in the retina occurred inferiorly. Fundus autofluorescence found hyperfluorescent changes corresponding to the preoperative location of the retinal vessels, suggesting an inferior rotation of the retina in 63% (27/43) of eyes. In those eyes with hyperfluorescent changes, a synoptophore measurement revealed that 59% of eyes had excyclotorsion and 49% of eyes had a vertical deviation. Interestingly, none of these eyes had symptomatic diplopia. Risk factors associated with retinal translocation included macula off status and increased size of retinal detachment. The use of perfluorocarbon liquid had no association with risk of retinal rotation.⁷⁸ Because it is often difficult to assure postoperative prone positioning without inadvertent upright positioning, placing the patient initially on their side with the temporal retina dependent in the early period after surgery may reduce the risk of inadvertent translocation.