Part V: Surgical Treatment for Age-Related Macular Degeneration

INTRODUCTION

In recent years, new treatment modalities such as photodynamic therapy and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have been added to the armamentarium of physicians treating age-related macular degeneration (AMD). Prior to the introduction of these therapies, the treatment options for AMD were more limited. At that time, only laser photocoagulation had been shown in a large randomized controlled trial to be effective for the treatment of subfoveal choroidal neovascularization (CNV) secondary to AMD. This trial, the Macular Photocoagulation Study, documented that laser photocoagulation of subfoveal CNV confers a statistically significant benefit with regard to long-term visual acuity (VA) when compared to the natural history of the condition (1–3).

Unfortunately, the Macular Photocoagulation Study also showed that the treatment of subfoveal CNV with laser photocoagulation was associated with an immediate average reduction of three Bailey– Lovie lines and the benefits of treatment over no treatment only became apparent six months after the treatment. In addition, retention or recovery of good

vision rarely occurred in patients treated with laser photocoagulation. For these reasons, many physicians worldwide did not use laser photocoagulation to treat subfoveal CNV, even at a time when it was the only treatment that had been proven effective by a large, well-designed, randomized clinical trial. This is nicely illustrated by a survey in 1999 of all consultant ophthalmologists in the United Kingdom and the Republic of Ireland by Beatty et al., which showed that only 13.6% of 339 ophthalmologists whose practice included laser photocoagulation of CNV secondary to AMD stated that they ablated subfoveal CNV with laser photocoagulation (4). The main reason (73.6%) the ophthalmologists gave for withholding treatment was that they were not prepared to accept the likelihood of an immediate drop in VA following laser ablation.

Investigators who pursued alternative therapy such as interferon alpha-2a (5–8), radiation (9,10), subretinal endophotocoagulation (11), and submacular surgery (12–17) also had no or limited success.

As a result of the limited treatment options in the pre-photodynamic therapy era, a number of investigators approached the management of subfoveal CNV with a totally new treatment paradigm. This

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treatment is known by several names including retinal relocation (18), retinal translocation (19,20), macular relocation (21–23), macular translocation (24–29), macular rotation (30), and foveal translocation (31–35). The term macular translocation is currently the most widely used (36). The popularity of macular translocation was highest in the few years prior to the introduction of photodynamic therapy in 2000 but has waned in recent years due to the wider availability of photodynamic therapy and the introduction of intravitreal anti-VEGF agents such as pegaptanib sodium, bevacizumab, and ranibizumab. However, it remains a potentially useful treatment option, and is still in use in some countries including the United States, Japan, and Germany. This chapter reviews the current status of macular translocation, with an emphasis on the two more widely used techniques, limited macular translocation and macular translocation with 3608 retinotomy.

CLASSIFICATION AND TERMINOLOGY

There are several different macular translocation techniques currently in use (36). These techniques produce different degrees of postoperative foveal displacement. The various forms of macular translocation may be broadly classified into three categories depending on the size of the retinotomy/retinotomies used: (i) macular translocation with 3608 peripheral circumferential retinotomy (21,22,24,37), (ii) macular trans-location with large (but less than 3608) circumferential retinotomy (31–35), and (iii) macular translocation with either small (self-sealing) or no

retinotomy/retinotomies, with or without chorioscleral infolding or outfolding (Fig. 1) (19,20,23,28,38,39). Macular translocation with 3608 retinotomy is also known as full macular translocation while another name for macular translocation with either small or no retinotomy/retinotomies is limited macular translocation.

RATIONALE

Although the exact pathogenesis of CNV secondary to AMD is not known, the natural history of this condition is progressive loss of central vision over time. The initial retinal dysfunction responsible for impaired vision in eyes with subfoveal CNV may be attributable to factors such as subretinal fluid, subretinal hemorrhage, and retinal edema. Accordingly, visual function may recover, at least partially, if these factors were removed. This improvement in macular function has been substantiated by focal electroretinography performed before and after macular translocation (40). When fibrous proliferation and degeneration of the overlying photoreceptors occur during the later stages of the disease, the visual loss becomes irreversible.

The rationale of macular translocation is that moving the neurosensory retina of the fovea in an eye with recent-onset subfoveal CNV to a new location before permanent retinal damage occurs may allow it to recover or maintain its visual function over a healthier bed of retinal pigment epithelium (RPE)– Bruch’s membrane–choriocapillaris complex. In effect, macular translocation attempts to achieve

a more normal subretinal space beneath the fovea. In addition, relocating the fovea to an area outside the border of the CNV allows ablation of the CNV by laser photocoagulation without destroying the fovea, thereby arresting the progression of the CNV and preserving central vision.

Some surgeons have combined macular translocation with submacular surgery. Thomas et al. have shown that removal of subfoveal CNV secondary to AMD is frequently accompanied by removal of native RPE, accounting for the relatively poorer visual outcome of submacular surgery for AMD when compared with that for other etiologies such as ocular histoplasmosis syndrome (15). This is because the CNV in AMD typically lies in the sub-RPE space between the RPE and Bruch’s membrane (type 1 CNV), as opposed to that found anterior to the native RPE in the sub-neurosensory retinal space (type 2 CNV) in eyes with ocular histoplasmosis, multifocal choroiditis, and idiopathic neovascular membranes (41). When combined with removal of CNV, macular translocation allows the fovea to be relocated to an area outside the RPE defect created.

HISTORICAL BACKGROUND

Lindsey et al. were the first to report their experiment with retinal relocation in 1983, but their aim was to study the anatomic dependency of the foveal retina on foveal RPE and choroid (18). Their techniques included creation of a retinal detachment and relaxing retinal incisions, shifting of the neurosensory retina and retinal reattachment. These techniques were expanded in 1985 by Tiedeman et al. who conceived the idea of rotating the macula of eyes with subfoveal CNV to a new area of underlying RPE–Bruch’s membrane–choriocapillaris complex as a treatment for the condition (42). They showed it was feasible to rotate the macula approximately 458 around the optic disc with reattachment of the fovea in animal eyes.

After developing their surgical techniques in rabbit eyes (21), Machemer and Steinhorst in 1993 became the first surgeons to demonstrate the feasibility of macular translocation in humans (22). Their technique involves lensectomy, complete vitrectomy, planned total retinal detachment by transscleral infusion of fluid under the retina, 3608 peripheral circumferential retinotomy, rotation of the retina around the optic disc, and reattachment of the retina with silicone oil tamponade. Besides allowing retinal rotation to occur, the retinotomy also provided access to the subretinal space to remove blood and choroidal neovascular membranes. A number of investigators subsequently modified this technique, but many of them still require large or 3608 retinotomy to allow rotation of the retina (26,30,31,37).

The early reports of proliferative vitreoretinopathy (PVR) complicating macular translocation with large retinotomy and 3608 retinotomy prompted Imai and de Juan to develop a new technique without the need for any retinotomy in 1996 (23). Their technique involves transscleral subretinal hydrodissection, anterior–posterior scleral shortening near the equator and retinal reattachment. Using this technique, they were able to achieve a predictable macular relocation of greater than 500 mm in rabbit eyes. As no retinal break was created, the likelihood of developing PVR was thought to be lower than that with earlier techniques. As they gained more experience with the surgery, de Juan et al. made additional modifications to their original technique (19,20,28,38). A 41-gauge retinal hydrodissection cannula is now used to make several tiny selfsealing retinotomies for subretinal hydrodissection to create a controlled, reproducible subtotal retinal detachment, and scleral resection during the scleral shortening procedure has been abandoned. They called this technique limited macular translocation since the operation achieves a smaller degree of postoperative foveal displacement and is less extensive compared with other techniques requiring large or 3608 retinotomy (43).

To increase the redundancy of the detached retina relative to the shortened eyewall, some investigators have modified the technique of scleral shortening from chorioscleral infolding to outfolding. Kamei et al. work in an animal model (44) and a clinical trial (39,45) demonstrated that radial outfolding with clips was a predictable and effective method of limited macular translocation. Since radial outfolding technique carries the risk of the choroidal fold affecting the macula, and because it is technically difficult to create a sufficiently long radial fold, the surgeons have changed their technique from radial to diagonal outfolding. Other investigators have used nonabsorbable sutures instead of clips to effect the outfolding (46).

INDICATIONS

Most surgeons use macular translocation to treat recent-onset exudative macular degeneration. However, some have also utilized it to treat nonexudative AMD and subfoveal RPE loss following submacular surgery.

Exudative Macular Degeneration

The most common application of macular translocation is in the management of recent-onset subfoveal CNV from a variety of etiologies. AMD is the most common indication given the high prevalence of this condition, but subfoveal CNV due to other causes

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such as pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, and multifocal choroiditis, as well as idiopathic neovascular membranes, have also been treated with this procedure (20). Some authors have reported better visual improvement after limited macular translocation for CNV secondary to pathologic myopia than for those due to AMD (47). It is possible to perform macular translocation for recurrent subfoveal CNV that develops after laser photocoagulation for initial nonsubfoveal CNV, although in such cases, the planned detachment of the macula is more difficult to achieve because the laser scar causes the retina to be more adherent to the underlying RPE (48).

Non-exudative Macular Degeneration

A small number of surgeons have used macular translocation to treat atrophic AMD (49–51). In a series of seven patients who had non-exudative AMD treated with macular translocation with 3608 retinotomy, five of the patients had improved distance and near vision (49). One of these patients developed a new area of geographic atrophy in the translocated fovea 12 months after surgery. This was similar to another patient who had apparent continued progression of geographic atrophy in the newly translocated macular region after effective macular translocation with 3608 retinotomy (51).

Subfoveal RPE Defect

Macular translocation is a potentially useful remedy for eyes with subfoveal RPE defect caused by submacular surgery. A case of a patient who underwent successful limited macular translocation for subfoveal RPE defect following submacular surgery for CNV secondary to ocular histoplasmosis syndrome has been described (52).

PREOPERATIVE CONSIDERATIONS

Proper case selection is crucial to good anatomic and functional outcome following macular translocation. A careful and detailed preoperative evaluation is therefore very important, and attention should be paid to the characteristics of the lesion in the macula as well as to concurrent pathology elsewhere in the retina. A recent good quality fluorescein angiogram, preferably obtained within one week of the surgery, is necessary to evaluate the characteristics of the CNV and its precise relationship to the geometric center of the foveal avascular zone. If limited macular translocation is planned, special care should be paid to the retinal periphery during indirect ophthalmoscopy with scleral depression to look for concurrent peripheral retinal pathology that may lead to operative complications.

Several preoperative pathophysiologic and anatomic factors are important in determining the postoperative functional and anatomic outcome of patients undergoing the procedure.

Pathophysiologic Considerations

Several pathophysiologic mechanisms responsible for visual loss in eyes with subfoveal CNV may have some bearing on the functional outcome following limited macular translocation. These factors may be broadly divided into “reversible” and “irreversible” components.

"Reversible" Components of Visual Loss

“Reversible” components of visual loss from subfoveal CNV secondary to AMD include (i) impaired photoreceptor function secondary to abnormal RPE function and impaired nutrient/waste exchange across the RPE and Bruch’s membrane, (ii) relative retinal ischemia/ hypoxia secondary to abnormal RPE–Bruch’s membrane–choriocapillaris complex, (iii) retinal edema and subretinal fluid, and (iv) retinal and subretinal hemorrhages. These problems may be evident early in the course of the disease, resulting in metamorphopsia and central blurring. Their effects are often not immediately devastating, and therefore affected eyes do not usually lose foveal fixation. Theoretically, effective macular translocation may, by reestablishing a relatively more normal subretinal space and underlying RPE–Bruch’s membrane–choriocapillaris complex, cause one or more of these factors to be reduced or reversed, thereby allowing visual recovery. The best candidates for surgery are therefore those with recentonset metamorphopsia or disturbance in central vision due to new or recurrent CNV, before massive subretinal fibrosis and degeneration of the photoreceptors permanently destroy the fovea.

"Irreversible" Components of Visual Loss

Untreated long-standing subfoveal CNV often results in permanent photoreceptor cell loss, an “irreversible” mechanism responsible for visual loss. This usually occurs in the late stages of the disease when there is fibrovascular scarring. Histopathologic studies have documented that the size and thickness of the disciform scar are directly related to the loss of photoreceptors (53). The visual loss associated with photoreceptor cell loss is often severe, but metamorphopsia becomes less prominent. Loss of foveal fixation may result from the severe visual impairment. Such a severely and irreversibly damaged foveal neurosensory retina is unlikely to achieve good functional recovery even after successful relocation to a healthier bed of RPE–Bruch’s membrane–choriocapillaris complex, and therefore is a poor candidate for limited macular translocation.

Proper case selection, by identifying patients with good photoreceptor function for surgery and excluding others with irreversible photoreceptor damage, is critically important to achieving good visual outcomes. The foveal function can be assessed preoperatively by a number of means including measurement of VA, scanning laser ophthalmoscope (SLO) microperimetry, and focal electroretinography (54). An analysis of a large series has shown that preoperative VA is a significant predictor of postoperative visual outcome, with good preoperative VA being associated with better postoperative visual results (55). However, eyes presenting with poorer vision have a greater chance of visual improvement but less likelihood of achieving excellent vision of 20/40 or better.

SLO microperimetry appears to be a useful way of identifying eyes that have viable foveal photoreceptors (54,56). It is particularly helpful in identifying patients who have maintained central fixation and may be a better indicator than VA in predicting good visual outcome following macular translocation.

Anatomic Considerations

Effective macular translocation may be defined as successful postoperative relocation of the fovea to an area outside the boundary of the lesion to be treated, i.e., when a more “normal” subfoveal space has been established. In the case of CNV, effective macular translocation is the successful postoperative relocation of the fovea to an area outside the border of the CNV i.e., a previously subfoveal CNV becomes either juxtafoveal (1 to 199 mm from the foveal center) or extrafoveal (R200 mm from the foveal center) following the surgery. If submacular surgery were combined with macular translocation, then effective macular translocation is the successful postoperative relocation of the fovea to an area outside the border of the RPE defect associated with CNV removal during the surgery.

Barring any complication, the anatomic success of macular translocation is dependent on two major factors: (i) the minimum desired translocation and (ii) the postoperative foveal displacement achieved. The minimum desired translocation can be measured prior to surgery and, when taken into consideration with the median postoperative foveal displacement normally achieved by the surgeon, can give some idea of the likelihood of achieving effective macular translocation following the surgery.

Minimum Desired Translocation

The minimum amount of foveal displacement required to achieve effective macular translocation is the distance between the foveal center and a point either on the inferior or superior border of the

D F

I

Figure 2 Schematic diagram showing fundus of the left eye. F is the foveal center, D is a point on the temporal edge of the optic disc, and I is a point on the inferior border of the subfoveal lesion (circle) such that DFZDI. The distance FI is the minimum desired translocation for an inferior translocation.

subfoveal lesion depending on whether the translocation is inferior or superior, all of these points being equidistant from the temporal edge of the optic disc. This distance is the minimum desired translocation

(Fig. 2). The temporal edge of the optic disc rather than the center of the disc is taken as the pivoting point of the fovea because the papillomacular bundle enters the optic disc from temporally close to this point. This is therefore the point in which the papillomacular bundle would pivot when the fovea is relocated during macular translocation.

Although the size of a subfoveal lesion is intuitively a factor in determining the minimum desired translocation, other factors such as eccentricity and shape of the lesion are important too. For example, in inferior macular translocation, a lesion that is eccentrically centered superiorly relative to the fovea has a smaller minimum desired translocation and is more likely to become juxtafoveal or extrafoveal following surgery compared with another lesion of the same size which is eccentrically centered downwards relative to the fovea, assuming that the net postoperative foveal displacement achieved is identical in both cases (Fig. 3). Lesions of the same size but of different shapes may also have different minimum desired translocations. On the other hand, lesions of different sizes and eccentricities may have the same minimum desired translocation (Fig. 4).

Median Postoperative Foveal Displacement

The median postoperative foveal displacement normally achieved by a surgeon can be derived by

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a

D F

I

b

D F

I

Figure 3 Schematic diagram showing the fundi of three eyes with subfoveal lesions (circles a, b, and c) of equal size but different eccentricities relative to the foveal center (F). Lesion a is centered eccentrically upwards relative to the foveal center (F), lesion b is centered on the foveal center (F), and lesion c is centered eccentrically downwards relative to the foveal center (F). D is a point on the temporal edge of the optic disc and I is a point on the inferior border of the subfoveal lesions such that DFZDI. The minimum desired translocation (FI) for inferior translocation is smallest for lesion a and greatest for lesion c. Lesion a is therefore more likely to achieve effective macular translocation compared with lesions b and c following inferior macular translocation.

C

B

A

D F

I

Figure 4 Schematic diagram showing ocular fundus with three possible subfoveal lesions (circles a, b, and c) of different sizes and eccentricities. F is the foveal center, D is a point on the temporal edge of the optic disc, and I is a point on the inferior border of the subfoveal lesions such that DFZDI. The minimum desired translocations (FI) for inferior translocation for lesions A, B, and C are identical. Lesions A, B, and C therefore have the same likelihood of achieving effective macular translocation following inferior macular translocation. Note, however, that the minimum desired translocations for superior translocation for lesions A, B, and C are different.

analyzing data collected either retrospectively or prospectively in a series of consecutive cases operated by the surgeon. To estimate the amount of translocation achieved, we first measure on the preoperative fluorescein angiogram the distance from a predetermined retinal landmark (such as a retinal vascular bifurcation) located superior to the CNV to a specific point along the inferior edge of the CNV. We then use the same points to obtain a similar measurement on the postoperative angiogram. The difference between these two measurements estimates the postoperative foveal displacement achieved (Fig. 5). If the time difference between the preoperative and postoperative angiograms is within two weeks, the size and characteristics of the CNV on the postoperative angiogram tend not to change significantly. Although this method of determining the postoperative foveal displacement is not very precise, especially for greater amounts of translocation, it does give useful estimates without the need to resort to sophisticated imaging equipment.

Ideally, a surgeon should have some idea of the median postoperative foveal displacement he or she has achieved in his or her previous cases when evaluating potential patients for macular translocation. This is particularly relevant for limited macular translocation. This information, when considered

together with the minimum desired translocation of a particular eye, gives some useful idea of the likelihood of achieving effective macular translocation. If the minimum desired translocation in an eye is equal to the median postoperative foveal displacement normally achieved by the surgeon, the eye has an approximately 50:50 chance of achieving effective macular translocation after the surgery, regardless of the other dimensions of the subfoveal lesion. If the minimum desired translocation is less than the median postoperative foveal displacement, the eye has a greater than 50% chance of achieving effective macular translocation. The chance of effective macular translocation is less than 50% if the minimum desired translocation is greater than the median postoperative foveal displacement for the surgeon. For example, if a surgeon has a postoperative foveal displacement greater than the patient’s minimum desired translocation in 75% of his previous cases, he could then tell his patient that he has an approximately 75% chance of effective macular translocation following surgery in his hands. If the macular translocation is combined with CNV removal, this rule may not apply if the area of the RPE defect accompanying the CNV removal differs greatly from the area of the original

CNV. This rule is more useful for limited macular translocation than for macular translocation with 3608 retinotomy since large amounts of postoperative foveal displacement are more readily achieved intraoperatively during the latter surgery. It is important to remember that the median postoperative foveal displacement for a particular surgeon is not static and may change with modifications or refinements in techniques.

OPERATIVE TECHNIQUE AND EARLY

POSTOPERATIVE MANAGEMENT

Limited Macular Translocation

Since the initial publications of the procedure (19,20,23), the technique has seen a number of modifications to improve the amount of translocation and to reduce the incidence of complications (28,38,55). Unlike other techniques that require the creation of large retinotomies to allow foveal displacement (22,31), limited macular translocation relies on scleral infolding or outfolding to shorten the outer eyewall (sclera, choroid, and RPE), creating redundancy of the neurosensory retina relative to the eyewall. Instead of large retinotomies, several small self-sealing posterior retinotomies are used.

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Limited macular translocation may be either inferior or superior. Inferior limited macular translocation causes inferior movement of the neurosensory macula relative to the underlying tissues and vice versa. Our experience with this surgery is that inferior limited macular translocation achieves a greater median postoperative foveal displacement than superior translocation for the same amount of scleral imbrication used. When the patient’s head is upright postoperatively, the buoyancy of the intravitreal air bubble supports the superior retina while the weight of the subretinal fluid stretches the retina inferiorly. These forces probably contribute to the greater downward displacement of the fovea during inferior macular translocation and reduce the upward displacement of the fovea during superior translocation. For this reason, inferior limited macular translocation is more commonly performed than superior limited macular translocation, which may be done for the occasional case in which the CNV is markedly eccentrically centered inferiorly relative to the fovea. The technique described below is for inferior limited macular translocation with chorioscleral infolding.

Overview/Equipment

Inferior limited macular translocation is essentially a five-step procedure (Table 1). The first step is placement of scleral imbricating sutures. The second step is a 3-port pars plana vitrectomy with separation of the posterior hyaloid face from the retina. The third step is creation of a neurosensory retinal detachment, with or without subretinal manipulation. The fourth step is tightening of the scleral imbricating sutures. The final step in the procedure is a subtotal fluid–air exchange.

The equipment necessary to perform this procedure includes a standard 3-port pars plana vitrectomy equipment. Additional devices that are unique to this procedure include (i) a 41-gauge retinal hydrodissection cannula (MADLAB retinal hydrodissection cannula, Bausch & Lomb Surgical, St. Louis, Missouri, U.S.A.) for subretinal hydrodissection to create a detachment of the neurosensory retina (Fig. 6), (ii) a specially designed retinal manipulator (Bausch & Lomb Surgical) for gently grasping the detached retina, aiding in the separation of the macular neurosensory retina from the RPE and also

Figure 6 Forty-one gauge retinal hydrodissection cannula (MADLAB retinal hydrodissection cannula, Bausch & Lomb Surgical, St. Louis, Missouri, U.S.A.).

permitting fluid–air exchange (Fig. 7), and (iii) a subretinal pick for subretinal dissection to break firm subretinal adhesions. In addition, we use an air humidifier (MoistAire humidifying chamber, RetinaLabs.com, Atlanta, Georgia, U.S.A.) that minimizes posterior capsular opacification in phakic patients (57) and potentially reduces excessive nerve fiber layer dehydration during the fluid–air exchanges (Fig. 8).

Operative Technique

Placement of Imbricating Sutures

We place three imbricating sutures in the superotemporal quadrant between the superior and lateral recti,

Table 1 Key Surgical Steps of Limited Macular Translocation

Placement of imbricating sutures Pars plana vitrectomy

Planned subtotal neurosensory retinal detachment Tightening of imbricating sutures

Subtotal fluid–air exchange

Figure 7 Retinal manipulator (Bausch & Lomb Surgical, St. Louis, Missouri, U.S.A.). The tip of the instrument is enlarged to show the three small openings of the retinal manipulator.

Figure 8 Air humidifier (MoistAire humidifying chamber, RetinaLabs Inc, Atlanta, Georgia, U.S.A.).

one suture just nasal to the superior rectus in the superonasal quadrant and one suture just inferior to the lateral rectus in the inferotemporal quadrant (Fig. 9). The number and actual location of the

Figure 9 Nonabsorbable imbricating sutures are placed straddling the equator of the globe prior to pars plana vitrectomy. The anterior scleral bites are placed 3 mm posterior to the recti insertion and the posterior scleral bites are placed 6 mm posterior to the anterior bites. Three imbricating sutures are placed between the SR and LR. The fourth imbricating suture is placed medial to the SR and the final one is placed inferior to the LR (not shown). Abbreviations: LR, lateral rectus; SR, superior rectus.

sutures have been selected empirically and are not based on precise data. The purpose of the imbricating sutures is to cause anterior–posterior shortening of the eyewall (sclera, choroid, and RPE) relative to the neurosensory retina. The sutures are placed in a mattress fashion and we use the same nonabsorbable sutures used for scleral buckling, i.e., either 4-0 silk or 5-0 dexon. The sutures are placed 6 mm apart from the anterior to posterior extent with the sutures straddling the equator. These sutures are not tightened until later on in the procedure.

Pars Plana Vitrectomy

Following preplacement of the imbricating sutures, vitrectomy is initiated. We prefer to fit the sclerostomies with metal cannulas for limited macular translocation because a “leaky” system is desirable during the creation of retinal detachment when balanced salt solution is injected into the subretinal space and during tightening of the imbricating sutures when the eye is deliberately kept soft. The metal cannula also facilitates the insertion of the delicate 41-gauge retinal hydrodissection cannula. Otherwise, the delicate cannula may be easily damaged during insertion through a sclerostomy. A subtotal vitrectomy is then performed. It is critical in these cases to be certain that the posterior hyaloid face is separated from the posterior pole, preferably up to the retinal periphery but at least past the intended positions of the posterior retinotomies. It appears that when the posterior hyaloid face has not been separated from the neurosensory retina, it tethers the neurosensory retina and reduces the amount of macular translocation. It is not necessary to trim the vitreous gel down to the vitreous base but the vitreous cavity needs to be debulked sufficiently to achieve a good air or gas fill.

Planned Neurosensory Retinal Detachment

To detach the retina, three to eight retinotomies are usually necessary. The preferred locations of initial retinotomy placement, which are just superior to the superotemporal vascular arcade and just inferior to the inferotemporal vascular arcade (Fig. 10). A third retinotomy is often necessary and is placed temporal to the macula (Fig. 11). The retinal detachments should be relatively large and need to extend in the superotemporal quadrant past the zone of intended imbrication. The 41-gauge retinal hydrodissection cannula is connected to an infusion pump to actively infuse balanced salt solution under the retina (Fig. 12). Prior to entering the vitreous cavity, the rate of infusion is set so that there is a steady drip of approximately two or three drops of balanced salt solution per second from the cannula. To initiate the subretinal blister, the 41-gauge retinal hydrodissection cannula is placed through the retina with the infusion

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Figure 10 The first retinotomy for subretinal hydrodissection is placed near the superotemporal vascular arcade to detach the superior retina.

Figure 11 The third retinotomy for subretinal hydrodissection is placed a few disc diameters temporal to the fovea to detach the temporal retina. The inferior retina had earlier been detached with a retinotomy placed near the inferotemporal vascular arcade. Note that the retinal detachment from the first retinotomy extends anteriorly beyond the zone of intended scleral imbrication.

Sclera

Figure 12 The retina is detached by injecting BSS between the neurosensory retina and the RPE with a 41-gauge retinal hydrodissection cannula through a tiny retinotomy. Abbreviations: RPE, retinal pigment epithelium; CNV, choroidal neovascularization; BSS, balanced salt solution.

running. The neurosensory retinal detachment will initially progress rapidly and tends to expand towards the retinal periphery. As the blister becomes larger, the expansion of the blister is slower although the infusion rate remains constant. If the cannula inadvertently becomes dislodged from the retinotomy during the procedure, one can usually reenter the same retinotomy and continue with the detachment. If this is not possible, a new retinotomy can be made in another site nearby. It is uncommon for the macula to become completely detached during this maneuver since the detachments have a tendency to progress anteriorly, presumably because the macula is relatively more adherent to the RPE than the retinal periphery.

The key to successful macular translocation is to completely detach the macula up to the temporal edge of the optic disc. At the same time, limit the detachment of the superonasal aspect of the retina because detachment of this area is associated with a higher risk of macular fold formation. The first step in completely detaching the macula is to perform a complete fluid–air exchange. The subretinal fluid will gravitate posteriorly and will usually dissect the macula off the underlying RPE (Fig. 13). When the macula is detached, the retinal bullae should extend to the optic nerve. However, this does not assure that all subretinal adhesions have been released. At this point, the air is exchanged for fluid, and inspection of the posterior retina with the aid of the retinal manipulator will confirm whether or not the macula is completely detached. If adhesions are present, the retinal manipulator can be activated with low suction to grasp a part of the detached retina. Gentle traction is then exerted with the retinal manipulator to release any persistent subretinal adhesion (Fig. 14). Care should be taken when using the retinal manipulator as it may result in iatrogenic retinal breaks, hemorrhage, macular hole,

Figure 13 A complete fluid–air exchange allows the subretinal fluid to gravitate posteriorly (white arrow) and dissect the macula off the underlying retinal pigment epithelium.

and nerve fiber layer injury (48). If despite these maneuvers, the retina is still not completely detached, a repeat fluid–air exchange can be performed. If repeated attempts fail to free a localized area of subretinal adhesion, such a laser scar, a small retinotomy is created eccentrically in the macula through which a retinal pick can be used to break the adhesions (Fig. 15).

Tightening of the Imbricating Sutures

Following the neurosensory retinal detachment (Fig. 16), when there is still fluid in the vitreous

RPE

Choroid

Retinotomy

Subretinal pick

Sclera

Figure 15 Subretinal blunt dissection (white arrows) with a pick through a small eccentric retinotomy may be necessary to break abnormal chorioretinal adhesions in the macula.

cavity, the imbricating sutures are tightened (Fig. 17). We tighten the sutures while the eye is filled with fluid rather than air to imbricate the eyewall under the bullous retina. Tightening the sutures while the eye is filled with air may cause the retina lying on the eyewall to be “caught” in the crevices of the imbrication and thus reduce the amount of retinal movement relative to the eyewall. To achieve adequate imbrication, the globe should be softened

Sclera

Figure 14 Gentle traction on the retina (white arrows) with a retinal manipulator helps to break abnormal chorioretinal adhesions and fully detach the macula from the retinal pigment epithelium.

Figure 16 A large retinal detachment temporal to an imaginary vertical line bisecting the optic disc is obtained following coalescence of the multiple smaller localized retinal detachments. It is important to ensure that the macula is completely detached and that the retinal detachment extends anteriorly beyond the zone of intended scleral imbrication.

Figure 17 Tightening the imbricating sutures (white arrow) causes the sclera to be imbricated under the detached retina and creates redundancy of the retina relative to the eyewall (sclera, choroid, and retinal pigment epithelium). Abbreviations: LR, lateral rectus; SR, superior rectus.

Figure 18 Following scleral imbrication, a final subtotal fluid–air exchange is performed without draining the subretinal fluid.

either by clamping the fluid infusion or leaving a sclerostomy open or both. There is a theoretical risk that this state of hypotony may increase the risk of intraocular hemorrhage such as suprachoroidal hemorrhage.

Although we perform anterior–posterior shortening of the eyewall with scleral imbrication in the majority of our cases of inferior limited macular translocation, it is interesting to note that this is not always necessary, and effective macular translocation may still be achieved without employing scleral imbrication for very small subfoveal lesions (28).

Subtotal Fluid–Air Exchange

The sclerostomy sites and peripheral retina are inspected for inadvertent retinal breaks prior to the final fluid–air exchange. If present, they should be treated with laser retinopexy or cryoretinopexy and a longer-acting gas such as sulfur hexafluoride is then used instead of air for internal tamponade.

The final fluid–air exchange is performed following tightening of the imbricating sutures (Fig. 18). An estimated 75% to 90% air–fluid exchange is carried out. The subretinal fluid is not completely drained as this tends to result in a smaller amount of macular translocation. After the sclerostomies and conjunctival incisions have been closed, a combination of corticosteroid–antibiotic subconjunctival injection is given. Intravenous corticosteroids may be given during the procedure to reduce the incidence of PVR.

Patient Positioning

After the eye is patched, the patient is turned on the operative side for about five minutes. This allows the subretinal fluid to gravitate temporally to detach the temporal peripheral retina. From this position (without turning the patient on his or her back), the patient sat upright and instructed to keep his or her head upright overnight. Besides allowing the temporal peripheral retina to be completely detached, this maneuver also causes all the subretinal fluid to accumulate in the inferior retina, reducing the incidence of a postoperative macular or foveal fold (Fig. 19). If the superonasal retina has been inadvertently detached during the surgery, sitting the patient upright from the supine position may cause some subretinal fluid to become trapped under the superonasal retina, causing a retinal bulla or retinal fold to overhang from the superonasal retina. This bulla or fold will often cause a retinal fold to stretch from the superior margin of the optic disc into the macula. When such a macular or foveal fold persists postoperatively, undesirable visual consequences occur and remedial surgery is usually necessary to unfold the macula.

The buoyancy of the intravitreal air bubble when the patient’s head is upright, coupled with the weight of the subretinal fluid inferiorly, stretches the retina in a downward fashion (Fig. 20). The superior retina is the first to become reattached, and this is quickly followed by the macula and the rest of the retina over the next several days.

Figure 19 The immediate postoperative head-positioning maneuver (see text) causes all the subretinal fluid to accumulate under the inferior retina. The inferior retina is detached. Note the scleral imbrication (white arrows) and the fluid–air interface in the vitreous cavity (black arrows).

Clinical Example

A 63-year-old man with a five-month history of decreased vision in his left eye due to neovascular AMD presented for consideration of macular translocation surgery. His best-corrected VA at presentation was 20/200K1. Clinical examination and fluorescein angiography confirmed a subfoveal CNV approximately one Macular Photocoagulation Study disc area in size (Fig. 21). After written informed consent was obtained, inferior limited macular translocation was performed without complication. Clinical examination and fluorescein angiography on the third postoperative day disclosed effective inferior translocation of the fovea relative to the CNV (Fig. 22). The postoperative foveal displacement achieved was approximately 700 mm. Laser photocoagulation was applied to the area of the CNV. The best-corrected VA improved to 20/60C 2 and 20/40 at four and eight months, respectively after the surgery. He had no postoperative complication or recurrence of the CNV during the follow-up period (Fig. 23).

Figure 20 With the head in an upright position following the surgery, the buoyancy of the air bubble supports the superior retina (white arrows) while the weight of the subretinal fluid stretches the retina downwards (black arrow), causing the fovea to be displaced downwards relative to the underlying eyewall (sclera, choroid and retinal pigment epithelium).

Combined Removal of CNV and Limited Macular Translocation

Some surgeons have advocated surgically removing the CNV at the time of limited macular translocation (27). We tend not to favor this approach, particularly in patients with AMD, because of the uncertainty in the size of the RPE defect that may occur. Thus, even though the preoperative CNV may be of a size and location that effective macular translocation would have a good chance of being achieved, the RPE defect created during submacular surgical excision may be significantly larger and therefore jeopardize the chances of anatomic success. We feel that laser ablation is a much more precise method of treating the CNV.

Postoperative Review, Fluorescein Angiography, and Laser Photocoagulation

On the first postoperative day, the macula is typically attached, although there is often subretinal fluid in the inferior retina. At this time, the presence of the intravitreal air bubble usually makes the fundus view too poor for fluorescein angiography. The patient continues to position his head upright until the retina becomes completely attached. Complete retinal reattachment generally occurs within two to three days. By three to seven days following the procedure, the reduced air bubble no longer covers

the macula when the patient is upright. At this point, it is appropriate to consider fluorescein angiography so as to identify the postoperative location of the CNV.

Interpretation of the postoperative fluorescein angiograms can be difficult in some cases given the additional retinal pigment epithelial changes induced by the surgical procedure. It is particularly important to obtain good quality angiograms and compare them with the preoperative angiograms to determine the actual location and extent of the CNV.

Figure 22 Three days following inferior limited macular translocation, fluorescein angiogram demonstrates effective macular translocation with displacement of the geometric center of the foveal avascular zone (arrow) to an area inferior to the choroidal neovascular membrane. The postoperative foveal displacement is approximately 700 mm.

Laser photocoagulation of the entire CNV lesion is considered following effective macular translocation when the CNV no longer lies under the geometric center of the foveal avascular zone. We follow the guidelines for laser treatment outlined in the Macular Photocoagulation Study (58). Following laser photocoagulation, the patient will be followed up in about three to four weeks with repeat fluorescein angiography to detect persistent or recurrent CNV.

Management of Persistent or Recurrent Subfoveal CNV

When some parts of the CNV remains under the center of the fovea due to insufficient macular translocation or when CNV recurs subfoveally after effective macular translocation and laser photocoagulation, the patient and physician must choose between a number of options including photodynamic therapy, intravitreal anti-VEGF injections, laser ablation of the fovea, or observation. Successful treatment of CNV with photodynamic therapy following insufficient macular translocation has been reported (59). The use of intravitreal anti-VEGF injections following macular translocation has not been reported but it could potentially be helpful. We do not advocate partial laser treatment of the CNV because it has been shown to be ineffective by the Macular Photocoagulation Study Group (60). Repeated attempts of macular translocation are also not recommended because initial efforts of this resulted in retinal detachment with significant PVR in some patients. One must consider that even when a CNV has not completely moved out of the foveal center, the partial movement may still benefit the patient as less of the perifoveal retina will need laser ablation.

Macular Translocation with 3608 Retinotomy

Macular translocation with 3608 retinotomy requires more manipulation than limited macular translocation, and is often combined with phacoemulsification or lensectomy with preservation of the anterior lens capsule (Table 2) (43,61,62). After a near-complete vitrectomy, the retina is detached totally with subretinal infusion of balanced salt solution and a 3608 peripheral circumferential retinotomy is performed with a vitreous cutter or vertical scissors near the ora serrata. Removal of the CNV or drainage of subretinal hemorrhage, if desired, is then performed under direct visualization. Some perfluorocarbon liquid is then injected onto the posterior retina after unfolding the retina. The retina is then rotated around its optic disk, usually with the fovea displaced superiorly. Additional perfluorocarbon liquid is then injected to fill the vitreous cavity, followed by endolaser photocoagulation to the retinal edges. Finally, the perfluorocarbon liquid is directly exchanged with silicone oil before the sclerostomies and conjunctiva are closed. The silicone oil is removed several months later, with or without an intraocular lens implantation. Corrective surgery for globe counter-rotation may be done during the primary surgery (43) or at a later date.

Table 2 Key Surgical Steps of Macular Translocation with 3608 Retinotomy

Phacoemulsification or pars plana lensectomy Pars plana vitrectomy

Planned total neurosensory retinal detachment 3608 circumferential peripheral retinotomy

Retinal rotation and reattachment with perfluorocarbon liquid and endolaser photocoagulation

Silicone oil exchange

MANAGEMENT OF POSTOPERATIVE

CYCLOVERTICAL DIPLOPIA

When the macula is moved sufficiently postoperatively, cyclovertical diplopia or awareness of a tilted image may occur in some patients. This is because the displacement of the fovea is around the optic disk and not directly upwards or downwards. This rotation of the retina can be measured using the Maddox rod test or the disk–fovea angle (63). This retinal torsion, coupled with the small range of fusional amplitude in the vertical direction, causes some patients to experience cyclovertical diplopia after successful macular translocation. As the degree of foveal displacement is relatively smaller following limited macular translocation compared with macular translocation with 3608 retinotomy, the incidence of postoperative cyclovertical diplopia is lower after limited macular translocation, and the symptoms may disappear spontaneously within a few months in many of these patients (27,43). For small degrees of cyclovertical diplopia, correcting the vertical component of deviation with vertical prism in glasses may allow the cyclodeviation to be compensated by the sensory fusion ability, which is driven by the central nervous system.

Three out of 10 patients who had limited macular translocation by Lewis et al. experienced either distortion or tilting of image postoperatively and these symptoms persisted for six months postoperatively in only one patient (27). Ohtsuki et al. evaluated 20 patients who underwent limited macular translocation and found seven of them (35%) experienced cyclovertical diplopia postoperatively (64). They treated these patients with transposition of the anterior superior oblique insertion with or without additional vertical

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muscle surgery. Six of the seven patients (85.7%) became unaware of tilted image while three of them (42.9%) had successful restoration of single binocular vision at distance and near.

Unlike limited macular translocation, macular translocation with 3608 retinotomy creates largeangle ocular torsion (30). This large magnitude and sudden onset of torsion causes disorientation and hinders use of the eye. Extraocular muscle surgery is usually required to decrease or eliminate torsion and improves the patient’s ability to function with the translocated retina. Several types of torsional muscle surgery for counter-rotation of the globe, sometimes with additional muscle surgery on the fellow eye, have been developed to reduce this complication (30,65–67). Following extraocular muscle surgery in a series of 63 patients who had undergone macular translocation with 3608 retinotomy, Freedman et al. were able to make 41% (23/63) of them free of both diplopia and tilt, while 5% (3/63) of patients had both symptoms constantly (66).

OUTCOME

Although histopathologic analyses of a single human case and three animal models have shown some minimal changes including a decreased photoreceptor density in the retina after macular translocation (19,68–70). One advantage of macular translocation over many other experimental or established treatment is that it offers the potential for improvement in VA (20,27,38,55). While some surgeons have found the results of macular translocation encouraging in some cases (20,55,71), others have found the surgery unpredictable (27,61).

The largest series of limited macular translocation by Pieramici et al. analyzed the outcomes of 102 consecutive eyes of 101 patients aged 41 to 89 years (median, 76 years) that underwent inferior translocation by one surgeon for new or recurrent AMD-related subfoveal CNV (55). The median postoperative foveal displacement achieved in the series was 1200 mm (range, 200–2800 mm). Seventy-five percent of the cases experienced at least 900 mm of postoperative foveal displacement and 25% achieved 1500 mm or more of foveal displacement. Sixty-two percent of the cases achieved effective macular translocation. At three and six months postoperatively, 31% and 49% of the eyes, respectively, achieved a VA better than 20/100 while 37% and 48% of the eyes, respectively, experienced R2 Snellen lines of visual improvement. Sixteen percent of the eyes experienced six or more Snellen lines of visual improvement. In a follow-up report on the same cohort of patients, 39.5% of 86 eyes with one-year follow-up experienced R2

Snellen lines of visual improvement, 29.0% remained unchanged, and 31.4% lost R2 lines of VA (72).

Pieramici et al. found that good preoperative VA, achieving the desired amount of postoperative foveal displacement, a greater amount of postoperative foveal displacement and recurrent CNV at baseline were associated with better VA at three and six months postoperatively (55). The reason patients with recurrent CNV achieved better outcome was thought to be that this select group of patients, having undergone previous laser photocoagulation for a juxtafoveal or extrafoveal lesion, were better educated about the necessity to see their ophthalmologist for any new visual change and were already on close follow-up by their ophthalmologist treating them. The subfoveal disease in this group of patients may therefore be of a shorter duration and less severe than those seen in patients who never had prior laser photocoagulation. Poor preoperative VA and the development of a complication either during or after surgery were associated with worse VA at three and six months postoperatively.

Ng et al. analyzed a consecutive series of 31 eyes of 29 patients who underwent limited macular translocation for recurrent subfoveal CNV after laser photocoagulation for initial nonsubfoveal CNV secondary to AMD (77.4%) and a variety of other pathologies (22.6%) (48). They achieved effective macular translocation in 77.4% of eyes. The postoperative foveal displacement ranged from 0 to 2230 mm (median, 1100 mm). Preoperatively, the VA ranged from 20/40 to counting fingers (median, 20/160), and 19% of eyes had VA better than 20/100. At six months, 54% of eyes achieved a VA better than 20/100, and 46% gained the equivalent of R2 Early Treatment Diabetic Retinopathy Study (ETDRS) lines. Subretinal dissection during the surgery to detach the macula was required in 25.8% of eyes and was associated with a significantly higher incidence of peripheral retinal breaks. Retinal detachment occurred in 19.4% of eyes, but the retinal detachment rate observed between the groups with and without subretinal dissection was not statistically significant (pZ0.30).

By selecting only patients with subfoveal CNV that did not extend more than half a disk diameter inferior to the fovea for inferior limited macular translocation, Morizane et al. was able to achieve effective macular translocation in all 12 eyes that underwent the surgery (73). This is not unexpected since the small minimum desired translocation is more likely to be associated with effective macular translocation (36). In this group of five patients with AMD and seven with polypoidal choroidal vasculopathy, the VA improved by R2 lines in 92% and remained within 1 line in 8%. In 58% of the eyes, the postoperative VA was 20/40 or better.

In a small series of 10 eyes of 10 patients with subfoveal CNV secondary to AMD treated by one surgeon, the median postoperative foveal displacement achieved was 1286 mm (range, 114–1919 mm) (27). The best-corrected VA, as measured with the ETDRS chart, improved in four eyes (median, 10.5 letters) and decreased in six eyes (median, 14.5 letters). The median change in VA for the entire series was a decrease of five letters. The final VA at six months postoperatively was 20/80 in two eyes, 20/126 in one eye, 20/160 in four eyes, 20/200 in one eye, 20/250 in one eye, and 20/640 in one eye.

Pawlak et al. compared the visual outcome of limited macular translocation with photodynamic therapy for subfoveal predominantly classic CNV in AMD in a nonrandomized retrospective review of 65 consecutive patients with follow-up of at least six months (74). A total of 29 eyes were treated with photodynamic therapy with verteporfin and 36 eyes underwent limited macular translocation. Both groups were similar for age, refraction, and lesion size, but the initial VA was lower in the macular translocation group (20/200) than in the photodynamic therapy group (20/100). At one year, both groups had the same final VA (20/200), but the improvement was more favorable in the macular translocation group (gain of 0.7 line in the macular translocation group versus loss of 3.4 lines in the photodynamic therapy group, pZ0.007). In the photodynamic therapy group, 4.3% of eyes had a gain of 3 lines or more versus 38% in the macular translocation group.

Using chorioscleral outfolding with titanium clips for macular translocation, Kamei et al. achieved larger postoperative foveal displacement with their modification of limited macular translocation than has been reported using chorioscleral infolding (39). They reported a median postoperative foveal displacement of 1576 mm (range, 349–3391 mm) in their series of 27 eyes followed up for more than two years compared with the 1200 mm reported by Pieramici et al. (55). In addition, because their outfolding technique required shortening of only 2 to 2.5 mm compared with 4 to 9 mm shortening for the infolding technique, there is less globe deformity and less induced corneal astigmatism (39).

It has been postulated that the scleral shortening with chorioscleral outfolding ought to be more than 12 times larger than with infolding (75). However, clinical studies have found the difference in techniques to result in a less profound difference in postoperative foveal displacement (39,45). Histopathologic analysis of the scleral imbrication site in one patient has revealed pleating of the sclera rather than distinct infolding (68). It is thought that this pleating of the sclera would reduce the scleral surface area at the imbrication site more than true infolding, thereby

explaining why the amount of postoperative foveal displacement is greater than expected with scleral infolding relative to outfolding.

In a series of 50 consecutive eyes with subfoveal CNV from AMD that underwent macular translocation with 3608 retinotomy and followed up for a median period of 21 months (range, 12–36 months), Pertile and Claes reported that the postoperative bestcorrected VA improved by R2 Snellen lines in 66%, remained stable (G1 line) in 28%, and decreased by R2 lines in 6% of eyes (76). The final best-corrected VA was 20/50 or better in 32% of eyes while 16% had a final best-corrected VA worse than 20/200. In another large series by Mruthyunjaya et al. of 61 AMD patients who underwent the same operation and followed up for 12 months, all eyes had successful translocation, and the median VA improved from approximately 20/125 before surgery to approximate 20/80 after surgery (77). The median reading speed also improved from 71 words per minute before surgery to 105 words per minute at 12 months after surgery. At 12 months, the VA improved R1 line in 52% of patients. A Japanese study of 23 AMD patients also showed a significant improvement in reading ability after macular translocation with 3608 retinotomy despite an absence of improvement in the distance and near VA (78). Another report by Toth et al. also showed improvements in distance VA, near-VA, contrast sensitivity, and reading speed in a series of 25 consecutive AMD patients who underwent the procedure (79).

Cahill et al. studied 50 patients’ quality of life (QOL) after macular translocation with 3608 retinotomy for AMD (80). They found that visionrelated QOL, as measured by the 25-item National Eye Institute Visual Function Questionnaire, improved after the surgery. Not surprising, the largest improvements in QOL were seen in patients with the greatest improvement in visual function, and the best postoperative QOL was seen in patients with the best postoperative visual patients.

Park and Toth evaluated the outcome of eight patients who underwent macular translocation with 3608 retinotomy for CNV secondary to AMD following at least one episode of photodynamic therapy with verteporfin (81). All of these patients had demonstrated continued visual loss following their most recent photodynamic therapy treatment. They found the final (mean follow-upZ10 months) mean VA change for patients who had only one prior photodynamic therapy session (five eyes) was C10 ETDRS letters and those who had multiple photodynamic therapy sessions (three eyes) was K1 ETDRS letter. They concluded that macular translocation with 3608 retinotomy may be a viable option to stabilize

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vision for patients who continue to lose vision in their better eye following photodynamic therapy.

In our experience, the most important aspects of macular translocation are patient selection, achieving the desired amount of macular translocation and avoiding complications. If this procedure is performed on a patient without viable foveal photoreceptors, there is no chance for visual improvement. If the minimum desired translocation is not achieved, we are left with a persistent subfoveal CNV lesion that will likely result in continued photoreceptor cell damage and visual deterioration. Development of a complication is associated with a poorer prognosis, particularly when retinal detachment occurs (55). To improve on the outcome of this surgery, care should be taken to select the appropriate patients and to reduce the incidence of complications.

COMPLICATIONS

The usual risks inherent to pars plana vitrectomy exist for all patients undergoing macular translocation since posterior vitrectomy is an integral part of the procedure. In addition, for patients who undergo limited macular translocation with chorioscleral infolding, additional risks similar to those associated with scleral buckling surgery are presented (Table 3). Table 4 shows the intraoperative and postoperative complications documented in Pieramici et al.’ series (55).

Intraoperative

Placement of sutures on the sclera for scleral imbrication may cause inadvertent scleral perforation. This may be associated with suprachoroidal hemorrhage,

Table 3 Complications Associated with Macular Translocation

vitreous hemorrhage, and retinal break. Retinal break can also occur during the later stages of the operation. The retina may be inadvertently cut or traumatized during vitrectomy. Vitreous traction near the sclerostomies, retinal incarceration at the sclerostomies and retinal manipulation during planned retinal detachment (27) may also tear the retina. Unintended retinal breaks occurred in 10 out of 102 consecutive eyes in Pieramici et al.’ series (55). Unintended nonselfsealing break(s) should receive laser retinopexy or cryoretinopexy during the surgery or in the early postoperative period. Longer-acting gas such as sulfur hexafluoride may also be necessary for internal tamponade. Macular hole formation is another complication that may also require longer-term internal tamponade.

During planned detachment of the retina, subretinal hemorrhage may occur if the retinal hydrodissection cannula used for subretinal hydrodissection or the subretinal pick used for blunt dissection traumatizes the vascular choroid. Unplanned translocation of the RPE can occur when a patch of RPE adherent to the underlying surface of the neurosensory retina detaches with the retina (38).

While the eye is deliberately kept soft momentarily to allow the imbricating sutures to be tightened, the eye is at risk of retinal incarceration at the sclerostomies and severe intraocular hemorrhage including suprachoroidal hemorrhage.

Postoperative

Rhegmatogenous retinal detachment is the most common serious complication of macular translocation. Nine out of 102 eyes in Pieramici et al.’ series developed persistent postoperative retinal detachment (55). Additional surgery is usually necessary to reattach the retina should this complication occur. Pneumoretinopexy may be effective in treating some cases with retinal breaks in the superior two-thirds of the retinal periphery. The retinal detachment may be associated with PVR, especially if a repeat limited macular translocation has been performed for persistent subfoveal CNV. Postoperative endophthalmitis is another potentially devastating complication.

The incidence of cataract formation appears to be similar to that following other vitrectomy procedures. Should cataract formation occur soon after limited macular translocation such as following intraoperative lens touch, it can impair visualization of the fundus postoperatively and interfere with clinical examination, fluorescein angiography, and laser photocoagulation. Early cataract surgery is indicated in such cases. Postoperative vitreous hemorrhage can also impair visualization and close follow-up with ultrasonography is warranted to look for associated retinal detachment.

Folds running across the fovea are associated with poor vision, and reoperation to remove the fold may be necessary. A foveal fold formed postoperatively in 3 of 10 eyes reported by Lewis et al. (27). A single case of a macular fold that developed after limited macular translocation was successfully treated with release of the scleral imbrication and intravitreal gas injection four days after the initial surgery (82). Interestingly, effective macular translocation was maintained despite the release of the scleral shortening. Presumably, the mechanism by which the translocated fovea did not return to its original position after scleral shortening released is the redundancy achieved by stretching of the neurosensory retina (82).

Induced corneal astigmatism is another complication of macular translocation. Not surprisingly, induced corneal astigmatism is more common after limited macular translocation than after macular translocation with 3608 retinotomy because chorioscleral infolding or outfolding deforms the globe (43). Between 1.75 and 7.37 diopters (mean, 4.6 diopters) of corneal astigmatism was found in a small series of eight eyes after macular translocation with chorioscleral infolding, with steepening along the axis of scleral shortening in the superotemporal quadrant of each eye (83).

Rarely, new CNV can occur at the site of the retinotomy used for retinal detachment, presumably as a result of iatrogenic focal defect in Bruch’s membrane caused by the retinal hydrodissection cannula. A case of severe hypotony has been reported after macular translocation with 3608 retinotomy (84). Two cases of transient formed visual hallucinations (Charles Bonnet syndrome) developing within 24 hours following limited macular translocation have been reported (85). The visual hallucinations ceased completely three to seven days postoperatively following retinal reattachment and associated visual improvement.

CONCLUSION

In this current era of photodynamic therapy and newer anti-VEGF injections, it is likely that the popularity of macular translocation for the treatment of CNV secondary to AMD will continue to wane. However, macular translocation does provide patients with a realistic hope of a shorter and more definitive treatment end-point when compared with photodynamic therapy and anti-VEGF injections where multiple retreatments are often necessary and the end-point of treatment sometimes uncertain. In eyes that continue to lose vision following photodynamic therapy, macular translocation may be a viable option to stabilize vision. In some countries where photodynamic therapy and anti-VEGF injections are either unavailable or yet to be approved, macular translocation remains a useful option for the treatment of certain subsets of patients with CNV.

SUMMARY POINTS

&Rationale. To displace the foveal neurosensory retina in an eye with recent-onset subfoveal CNV to a presumably healthier bed of RPE–Bruch’s membrane–choriocapillaris complex devoid of CNV before permanent retinal damage occurs; the foveal displacement allows the destruction of the CNV by laser photocoagulation without damaging the foveal center.

&Indications. Subfoveal CNV secondary to a variety of etiologies including exudative AMD. Some surgeons have also performed the operation on nonexudative AMD.

&Classification of macular translocation. The various forms of macular translocation may be broadly classified into three categories depending on the size of the retinotomy/retinotomies used: (i) macular translocation with 3608 peripheral circumferential retinotomy, (ii) macular translocation

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with large (but less than 3608) circumferential retinotomy, and (iii) macular translocation with either small or no retinotomy/retinotomies.

&Complications. Intraoperative complications include scleral perforation, unplanned retinal break, intraocular hemorrhage, macular hole, unplanned translocation of RPE and postoperative include rhegmatogenous retinal detachment, PVR, endophthalmitis, cataract, intraocular hemorrhage, foveal fold, new CNV at site of retinotomy, acute angle-closure glaucoma, and transient formed visual hallucinations.

&Role of macular translocation in current era of photodynamic therapy and anti-VEGF therapy. Macular translocation offers a realistic hope of a shorter and more definitive treatment end-point compared with photodynamic therapy and anti-VEGF therapy where multiple retreatments are often necessary and the end-point of treatment sometimes uncertain. However, because of its higher risk of complications, its popularity has waned since the advent of photodynamic therapy. It remains a useful option when these newer therapies are unavailable.

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macular function after retinal translocation surgery in a patient with age-related macular degeneration. Am J Ophthalmol 2000; 129(4):547–9.

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44.Kamei M, Roth DB, Lewis H. Macular translocation with

chorioscleral outfolding: an experimental study. Am J Ophthalmol 2001; 132(2):149–55.

45.Lewis H. Macular translocation with chorioscleral outfolding: a pilot clinical study. Am J Ophthalmol 2001; 132(2):156–63.

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48.Ng EWM, Fujii GY, Au Eong KG, et al. Macular translocation in patients with recurrent subfoveal choroidal neovascularisation after laser photocoagulation for nonsubfoveal choroidal neovascularization. Ophthalmology 2004; 111(10):1889–93.

49.Eckardt C, Eckardt U. Macular translocation in nonexudative age-related macular degeneration. Retina 2002; 22(6):786–94.

50.Cahill MT, Freedman SF, Toth CA. Macular translocation with 360 degrees peripheral retinectomy for geographic atrophy. Arch Ophthalmol 2003; 121(1):132–3.

51.Khurana RN, Fujii GY, Walsh AC, Humayun MS, de Juan E, Sadda SR. Rapid recurrence of geographic atrophy after full macular translocation for nonexudative age-related macular degeneration. Ophthalmology 2005; 112(9):1586–91.

52.Fujii GY, de Juan E, Thomas MA, Pieramici DJ, Humayun MS, Au Eong KG. Limited macular translocation for the management of subfoveal retinal pigment epithelial loss after submacular surgery. Am J Ophthalmol 2001; 131(2):272–5.

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65.Freedman SF, Rojas M, Toth CA. Strabismus surgery for large-angle cyclotorsion after macular translocation surgery. J AAPOS 2002; 6(3):154–62.

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360-degree peripheral retinectomy following ocular photodynamic therapy of choroidal neovascularization. Am J Ophthalmol 2003; 136(5):830–5.

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INTRODUCTION

Adjuncts that have been used in surgery for age-related macular degeneration (AMD) include tissue plasminogen activator (tPA), balance salt solution (BSS), and calciumand magnesium-free retinal detach- ment-enhancing solutions. The surgeries in which these solution have been used include submacular surgery to excise choroidal neovascular membranes, large-scale macular translocation surgery, limited macular translocation surgery, evacuation, or displacement of submacular hemorrhages. In addition to these adjuncts, triamcinolone acetonide (TA) has been injected into the subretinal space for the treatment of choroidal neovascular membranes.

Novel surgical approaches include the surgical implantation of sustained release drug devices, the surgical implantation of cell-based delivery systems, and the pre-retinal or subretinal delivery of radiation therapy through a pars plana approach.

TISSUE PLASMINOGEN ACTIVATOR

tPA is a polypeptide of 527 amino acids that cleaves the Arg560-Val561 bond of plasminogen. Because of its high affinity for fibrin, its enhancement of binding of plasminogen to fibrin clots, and potentiation of its activity in the presence of fibrin, fibrinolysis occurs almost exclusively in fibrin clots.

Commercial tPA (Activase, Genentech, Inc.; Actilyse, Boehringer Ingelheim International, GmbH) is a 70,000 mW, single-chain protein produced from a cloned human tPA gene using Chinese hamster ovary cells (1). Endogenous tPA is secreted in its single-chain form to be enzymatically converted by plasmin to its two chain form. Both forms of tPA are equally active. The vehicle consists of L-arginine phosphate, phosphoric acid, and polysorbate 80. tPA has been used both intracamerally and subretinally. The utility of intracameral tPA was demonstrated in animal models of fibrin (2–4), hyphema (5), vitreous

hemorrhage (6–8), and subretinal hemorrhage (9,10). The utility of subretinal injection of tPA was demonstrated in animal models of subretinal hemorrhage (11–13).

In the anterior chamber, 0.05 mL containing up to 200 mg and 0.10 mL containing up to 360 mg have been injected without unusual inflammation or toxicity to the cornea or lens. In the vitreous cavity, 0.10 mL containing up to 25 mg has been injected without corneal or retinal toxicity. Repetitive injections (three times, separated by seven-day intervals) of 3 mg tPA also did not show retinal toxicity (8). A single report suggested probable retinal toxicity of 0.1 mL containing 25 mg (14). Dose-dependent retinal toxicity was seen with 0.10 mL injections of 50, 75, and 100 mg into the vitreous cavity (15). Tractional retinal detachments were seen following 100 mg (6) and 200 mg (7) tPA injections.

In the subretinal space, no retinal toxicity was seen after subretinal injection of 25 and 50 mg of tPA in 0.1 mL of volume (11,12).

Lewis and colleagues demonstrated in rabbits that subretinal clots, 30-minutes old, cleared faster after a 0.1 mL subretinal injection of 25 mg tPA as compared to an equivalent volume of BSS (11). However, the subretinal tPA could not completely prevent retinal damage. Both BSS and tPA decreased the toxic effect of blood partly on the basis of dilution of the subretinal blood. Johnson and colleagues showed a similar effect for lower doses of tPA (2.5 mg in 0.05 mL) on clots that were 24-hours old, but severe progressive retinal degeneration was still seen (12). An ultramicrosurgical approach using a microinfusion of 0.5 to 5 mg of tPA facilitated lysis of oneand two- day-old clots and their removal through micropipettes under stereotactic control. Good preservation of the retinal architecture was seen compared to untreated controls (13).

The ability of intravitreal injections of tPA to lyse subretinal clots has been explored. Coll and colleagues found that 0.1 mL containing 50 mg of tPA facilitated

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the lysis and absorption of one-day-old subretinal clots compared to equivalent volume injections of saline (9). Unfortunately, retinal damage was not prevented. Boone and colleagues injected 25 mg of tPA into the vitreous space and found only partial clot lysis that was not enough to allow removal by aspiration alone (10). The inability of labeled tPA injected into the vitreous to penetrate the intact neural retina or a subretinal clot in rabbits was demonstrated by Kamei and colleagues (16). Some labeled tPA was able to penetrate into eyes with vitreous hemorrhage presumably from the microdefects through which blood escaped from the subretinal space into the vitreous.

The previous studies spurred simultaneous interest in the clinical use of tPA to assist in the removal of subretinal hemorrhage. These techniques involved the injection of 6.25 to 12.5 mg of tPA in a volume of 0.05 mL into the subretinal space and then waiting 10 to 45 minutes before aspiration of the liquefied blood. Injections into the subretinal space were accomplished with a glass pipette (17), 33-gauge cannula (18), or bent-tipped 30-gauge needle (19,20). Aspiration was performed with double-barrel subret- inal-injector aspirator (18), soft-tipped cannula (17,21), tapered 20-gauge Charles flute needle (20), or 30-gauge subretinal cannula (22). Liquefied subretinal blood was also manipulated with a small perfluorocarbon liquid bubble (19,23,24).

In addition to intravitreal injection of tPA during the pars plana vitrectomy procedure, the injection of 0.1 mL of 25 mg of tPA into the subretinal clot by passing a 30-gauge needle through the pars plana under indirect ophthalmoscopy the day before pars plana vitrectomy has also been described (25).

An intravitreal injection consisting of 6 mg of tPA in 0.1 mL was injected into the midvitreous cavity to liquefy subretinal clots 12 to 36 hours prior to vitrectomy and removal of blood through a retinotomy using perfluorocarbon liquid manipulation (26). Intravitreal injections of 0.1 to 0.2 mL containing 25 to 100 mg of tPA into the vitreous cavity have been given either the day before (27) or immediately before (28,29) injection of intravitreal gas to displace submacular hemorrhage. Exudative retinal detachments seen after 100 mg injections were attributed to tPA toxicity (28).

A number of investigators have injected 25 to 50 mg tPA into the subretinal space following pars plana vitrectomy (30–32).An air fluid exchange was performed and the patient was kept erect to pneumatically displace the liquefied blood from the fovea.

Lewis injected tPA into the subretinal space before excision of the choroidal neovascular membrane but found no improvement compared with injection of BSS into the subretinal space in a randomized trial (33).

CALCIUMAND MAGNESIUM-FREE RETINAL DETACHMENT-ENHANCING SOLUTIONS

Marmor had discovered that removing calcium and magnesium from a solution that bathed eye wall sections in vitro weakened retinal adhesive force (34). Wiedemann described a “detachment infusion” for macular translocation surgery that was calcium and magnesium free (35). Substituted for conventional vitrectomy infusion fluid, this solution enabled the immediate detachment of the retina from its peripheral, diathermy-induced perforation site to the center of the macula or macular area. He described its use in retinal organ culture and creation of experimental retinal detachment in rabbits and in human surgery.

We hypothesized that BSS Part A might be an ideal retinal detachment-enhancing solution and studied its safety and efficacy in rabbits before using it clinically in humans. BSS was developed as an improvement over normal saline, lactated Ringer’s, and Plasma-lyte 148 as a physiologically compatible solution to be used in the eye during surgery (36,37). To further improve the physiological compatibility of BSS, glutathione, glucose, and bicarbonate buffer systems were added (38–40) resulting in BSS Plus. BSS Plus consists of two parts, which are reconstituted just prior to use in surgery. These two parts consist of Part B, a sterile 480-mL solution in a 500-mL singledose bottle to which Part A, a sterile concentrate in a 20-mL single-dose vial, is added. Compared to BSS, BSS Part A lacks magnesium and calcium, and the citrate and acetate buffers of BSS have been replaced with bicarbonate buffer. BSS Part B contains calcium and magnesium as well as the dextrose and the glutathione, which are unique to BSS Plus. We hypothesized that BSS Part A alone could be used safely in the human eye since it contained almost all the ingredients of BSS except for the calcium and magnesium with a different buffering system and a pH of 7.4. A tremendous advantage to the vitreous surgeons is the commercial availability of BSS. We felt that all these qualities plus the historical use of the solution in the operating room (albeit reconstituted with Part B) could make it an ideal solution to enhance retinal detachment during macular translocation surgery. We showed the safety and efficacy of a calciumand magnesium-free macular translocation solution by comparing the results of injecting BSS Part A or BSS solution into the subretinal space of rabbit eyes using a 39-gauge cannula (40). No difference was seen in fundus appearance, fluorescein angiography, electroretinography, or light or electron microscopy in rabbit retinas that had been detached using retinal detachment solution compared to commercially available solution. Using a manual infusion system, no more than 100 mg of BSS compared to a much larger

volume of retinal detachment solution could be infused into the subretinal space. The diameter of BSS retinal detachments was always less than that of BSS Part A retinal detachments after injection of 100 mg of subretinal fluid.

Aaberg et al. have similarly shown the safety of subretinal BSS Part A in the sub-retinal space of the rabbit using transscleral infusion (41).

We have used a 39-gauge cannula to atraumatically infuse BSS Part A underneath the retina in macular translocation surgery and to displace submacular hemorrhage.

Clinically, we have found that macular translocation surgery requires only one or two penetrations through the retina with a 39-gauge cannula to detach the posterior retina sufficiently. We have used BSS Part A to displace submacular hemorrhages by performing pars plana vitrectomy, injecting the solution to detach the posterior pole of the retina, performing partial gas– fluid exchange, and then positioning the patient in an erect position for 24 hours to displace blood away from the fovea.

TRIAMCINOLONE ACETONIDE

A discussion of the pharmacology and the mechanism of action of TA is presented in Chapters 8 and 15. The intravitreal injection of TA for the treatment of choroidal neovascular membranes is also discussed in those chapters. The subretinal injection of TA will be discussed here.

SUBRETINAL INJECTION OF TA

Some current methods for treating retinal diseases involve the introduction of drugs directly into the vitreous chamber of the eye by intraocular injection or intravitreal implant. Solutions injected directly into the vitreous chamber, however, are often rapidly removed by the eye’s normal circulatory processes, requiring frequent injections or sustained release of the drug. These large-dose injections lead to the distribution of the drug throughout the whole eye and can be associated with complications, such as cataract formation and glaucoma. Additionally, these therapies do not address the issue of large molecular weight molecules (more than 70 kDa) that are virtually incapable of diffusing through retinal tissues.

The delivery of TA into the subretinal space has been investigated for the treatment of subfoveal choroidal neovascularization (CNV) due to AMD. The subretinal delivery of a therapeutic agent could allow for the local, low-dose treatment of retinal pathology with fewer complications to other intraocular structures such as the lens and optic nerve. These subretinal injections can be delivered through

Figure 1 Forty-one gauge subretinal cannula in the extended position.

a 41-gauge cannula (Figs. 1 and 2) and the retinal openings that are created self-seal and do not need to receive retinopexy. In our institution, we have performed these injections after removal of the vitreous by pars plana vitrectomy and through formed vitreous without vitrectomy. These injections have been performed both in the operating room and in the clinic setting.

In a pilot study, two eyes of two patients underwent pars plana vitrectomy, subretinal injection of 4 mg of TA (0.1 mL), and gas–fluid exchange for subfoveal neovascular AMD (42). The first patient sustained a limited subretinal hemorrhage intraoperatively that cleared spontaneously over approximately three months, as well as a rise in intraocular pressure that required the use of two topical medications to control. The second patient demonstrated progression of his nuclear sclerosis and posterior subcapsular lens

Figure 2 The body of the 41-gauge subretinal cannula has a sliding button which can be used to extend and retract the cannula itself.

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change over the 35 months of follow-up. Best corrected visual acuity improved from 20/400 to 20/200 in the first patient, and from counting fingers to 20/320 in the second patient. The size of the neovascular complexes increased modestly in both patients. The authors conclude that their complications were not prohibitive, and that their results may be likened to the course seen with PDT.

A pilot study of 14 eyes of 14 patients with subfoveal CNV from AMD was performed where 0.5 to 5 mg of TA was injected subretinally, overlying the CNV (43). Three patients developed a subretinal hemorrhage in the immediate postoperative period, where two of these three patients’ final visual acuities improved (Fig. 3). Also, in the immediate postoperative period, one patient had an elevated intraocular pressure and one patient had a retinal detachment. There were no late postoperative complications.

Although subretinal delivery of triamcinolone seems to be safe, maximizing durability of drug and minimizing injections is desirable. Therefore, a biocompatible, sustained-release subretinal drugdelivery platform has been developed which is capable of delivering either TA or sirolimus (44). The prototype implants were fabricated by coating nitinol, poly(methyl methacrylate) or chromic gut core filaments, with a drug-eluting polymer matrix, and tested in rabbits (Fig. 4). Initial observations of the implantation and elution characteristics revealed that the implants are well tolerated by the retinal tissue and that the implant can elute TA for a period of at least four weeks without eliciting an inflammatory response or complications.

Figure 3 After subretinal injection, the triamcinolone is located inferior and temporal to the fovea. There is hypopigmentation at the site of the injection which is located between the white mass and the fovea.

Figure 4 The drug-releasing filament lies under the retina in this rabbit.

ENCAPSULATED CELL TECHNOLOGY

Encapsulated cell technology (ECT) employs mammalian cells that are genetically engineered to secrete a therapeutic factor. These engineered cells are then encapsulated in a semi-permeable polymer membrane device which allows for the free exchange of nutrients and metabolites to sustain the cells, while allowing for the exit of a therapeutic factor (Figs. 5 and 6). At the same time, these membranes protect the engineered cells from host antibodies and immune cells. The devices are then surgically implanted into the vitreous cavity of the eye (Fig. 7). ECT allows for the continuous and long-term site-specific administration of drugs in the eye without subjecting the host to systemic exposure. Furthermore, these implants can be retrieved, providing an added level of control and safety.

ECT-CNTF (human ciliary neurotrophic factor) devices were implanted in a dog model of retinitis pigmentosa (RP) (45). One eye was implanted at seven weeks of age, leaving the contralateral eye untreated. These devices were explanted at 7 or 14 weeks postimplantation. There was significant protection of the photoreceptors from degeneration in a dose-depen- dent and safe manner, as revealed by examining the number of cells in the outer nuclear layer histologically. Furthermore, the data from this study confirmed that sustained delivery of protein therapeutics is more effective than bolus injection, while avoiding the additive risks of frequent intraocular injections. The authors also concluded that this technology was superior to the use of viruses in gene therapy, as gene therapy tended to be effective only for a few weeks, induced an immune response, and produced unpredictable amounts of therapeutic agent.

These data from animal studies enabled a prospective phase I clinical trial which safely delivered CNTF to the eyes of 10 subjects suffering from advanced RP (46). Though this nonrandomized trial

had only a small number of participants and was not placebo-controlled, several of the implanted eyes showed a trend of better acuity on a letter recognition task compared with contralateral control eyes. At the end of the six-month implantation duration, all explanted capsules contained viable cells that secreted CNTF at expected levels that were therapeutic in the rcd1 (cGMP-PDE6b mutation) dog study (45).

Smaller ECT devices that can be implanted through a 25-gauge opening are currently being developed (47). The application of this technology to other ocular diseases such as AMD is currently an active area of investigation.

SELECTIVE INTRAOCULAR RADIATION

BRACHYTHERAPY

Although the results of radiation treatment for neovascular AMD are mixed and generally unfavorable (48,49), there is data to suggest that higher dosages may produce better results (50–53). Flaxel and colleagues showed promising results with proton beam radiation at 8 to 14 Gray (Gy), but radiation

Figure 6 Living cells that release therapeutic molecules are encased in a proprietary scaffold, which serves as the semipermeable membrane to create the cell-based drug delivery device.

Figure 7 The cell-based drug delivery device is anchored by suturing an attached titanium ring to the pars plana.

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retinopathy was a serious complication and seen in 50% of the 14 Gy-treated eyes (54).

To overcome this limitation in radiation delivery dosage caused by radiation retinopathy, a method of delivering focal radiation to the choroidal neovascular membrane by passing an intraocular radiation delivery device underneath the retina was developed. Retina exposure to radiation is minimized by directional shielding of the subretinal radiation source and by the focal nature of the radiation delivery. Creation of a subretinal bleb using a 41-gauge needle and a retinotomy allowed for the brachytherapy probe to be in direct contact with the retinal pigment epithelium (RPE) for a set amount of time. The brachytherapy device contains shielding which prevent radiation exposure on the retinal side.

In a phase I clinical study, 10 eyes of 10 patients received 26 Gy of subretinal radiation via an angled or non-angled probe to active subfoveal CNV, with follow-up ranging from two to nine months (55). By fluorescein angiography, greatest linear dimension (GLD) leakage decreased by 46% in one month, 64% in three months, and 82% in six months. By optical coherence tomography, total macular volume decreased by 13% in one month, 19% in three months, and 30% in six months. Visual acuity was stable or improved in 44% by two and three months. Adverse events included RPE tears, RPE atrophy, RPE hyperpigmentation, subretinal hemorrhage, cataract, pre-retinal hemorrhage and vitreous hemorrhage.

Because of these complications, efforts are now directed towards pre-retinal delivery of radiation. Preclinical study showed that the minimum threshold for acute damage using a pre-retinal focal radiation delivery device was above 103 Gy, nearly four times the dosage expected to cause beneficial effect described in the literature. As a result, a phase I clinical trial is in the planning stage to evaluate the safety and feasibility of focal delivery of radiation from a preretinal position using a sealed radiation source placed temporarily over the fovea in the vitreous cavity by means of a proprietary intraocular probe. The delivery device is a shielded canister containing a strontium90 beta-radiation source with an angled-tip that has a 1.0 mm outer diameter. In the storage (retracted) position, the radiation source is surrounded by a stainless steel and lead lining that effectively protects the surgeon and patient during the handling and initial positioning. This tip will allow for the directional delivery of approximately 24 Gy of betaradiation via a light touch approach on the retinal surface for a three to five minute period. In the treatment position, the source is located within a specially designed stainless steel tip that provides directional administration of the beta radiation while

Figure 8 In a retracted position, the radiation source lies in the body of the delivery instrument and is shielded from the environment. The sliding button is used to extend the radiation source into the curved tip for radiation of the choroidal neovascular membrane.

shielding and protecting surrounding non-target, unaffected (i.e., disease free) tissues (Figs. 8 and 9).

SUMMARY POINTS

&Adjuncts are used primarily in the subretinal space during surgery for AMD.

&tPA can be infused into the subretinal space to liquefy subretinal blood.

&tPA may penetrate human retina after injection into the vitreous cavity through microperforations to liquefy subretinal blood.

&Calciumand magnesium-free solutions enhance retinal detachment.

&BSS Plus Part A is a safe and readily available retinal detachment solution.

&Calciumand magnesium-free solutions can aid macular translocation surgery and the displacement of submacular hemorrhage.

Figure 9 Delivery device for intraocular radiation brachytherapy.

&Novel surgical approaches seek a long term enhancement of existing therapies for AMD. These approaches include the surgical implantation of sustained release drug devices, the surgical implantation of cell-based delivery systems, and the pre-retinal or subretinal delivery of radiation therapy through a pars plana approach.

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