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   Table of Contents      
CURRENT OPHTHALMOLOGY
Year : 1997  |  Volume : 45  |  Issue : 2  |  Page : 77-92

Submacular surgery


Barnes Retina Institute, St. Louis, Missouri 63110, USA

Correspondence Address:
S Saxena
Barnes Retina Institute, St. Louis, Missouri 63110
USA
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Source of Support: None, Conflict of Interest: None


PMID: 9475025

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  Abstract 

Modern vitreoretinal surgery is now one of the most effective tools for treating posterior segment diseases. In the last several years, there has been a surge of interest in submacular surgery which allows removal of submacular choroidal neovascular membranes and haematomas. Various aspects of this rapidly emerging modality of surgery are discussed in this review.

Keywords: Submacular surgery, choroidal neovascularization, submacular haemorrhage, vitrectomy


How to cite this article:
Saxena S, Thomas M A, Melberg N S. Submacular surgery. Indian J Ophthalmol 1997;45:77-92

How to cite this URL:
Saxena S, Thomas M A, Melberg N S. Submacular surgery. Indian J Ophthalmol [serial online] 1997 [cited 2021 Mar 6];45:77-92. Available from: https://www.ijo.in/text.asp?1997/45/2/77/15011



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Modern vitreous surgery through pars plana is now one of the most effective tools for treating posterior segment disease. Removal of scar tissue and blood that interfere with retinal function is the main stay of vitreous surgery. With refinement in techniques and instrumentation, extensive surgical manipulation within the vitreous cavity can now be performed with resulting improvement or stabilization of visual function. Innovative and exciting developments in the relatively new field of macular surgery offer great promise to patients with many diseases that were previously thought to be incurable.[1] During the past few years, increasing attention has been given to applying similar techniques in the submacular area, which allow removal of choroidal neovascular membranes and haemorrhage.


  I. SUBFOVEAL CHOROIDAL NEOVASCULARIZATION Top


Choroidal neovascularization (CNV) is the principal cause of loss of central visual function in adults. Choroidal neovascular membranes are most frequently caused by age related macular degeneration (ARMD) and presumed ocular histoplasmosis syndrome (POHS), although neovascularization may be observed as a complication of other ocular conditions.[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Choroidal neovascular membranes disrupt normal macular anatomy (including critical photoreceptor-retinal pigment epithelial interface), leak serum and or formed blood elements and lead to irreversible loss of overlying photoreceptors.[17] When fibrovascular membranes grow beneath the centre of the foveal avascular zone, the visual prognosis is generally poor.


  Natural History Top


Bressler et al[18] found that 70% of eyes with subfoveal membranes, secondary to ARMD, had visual acuities of 6/60 or worse within 2 years. The Macular Photocoagulation Study[19] reported 3- and 4-year outcomes in eyes followed up in two randomized clinical trials of laser photocoagulation for subfoveal CNV secondary to ARMD. Four years after enrollment in the subfoveal new CNV study, 39 (47%) of 83 untreated eyes and 17 (22%) of 77 laser-treated eyes had lost 6 or more lines of visual acuity from baseline levels. At the 3-year examination in the subfoveal recurrent CNV study, 21 (36%) of 58 untreated eyes and six (12%) of the treated eyes had lost 6 or more lines of visual acuity from baseline levels. Eyes with POHS do better. Olk et al[20] and Kleiner et al[21] reported that as many as 14% may retain visual acuity of 6/12 despite subfoveal vessels. Ninety percent of eyes with visual acuity of 6/ 60 or less still will have severely reduced visual acuity after 3 years. Campochiaro et al,[22] reported that only 7% of membranes in eyes with CNV, secondary to POHS, undergo spontaneous involution with improvement in visual acuity. Fibrovascular membranes usually continue to grow without treatment. Vander et al[23] documented an average growth rate of 9 m daily in eyes with neovascular membranes in ARMD.


  Management Top


The objective in treating CNV is to destroy the abnormal neovascular tissue and limit these damaging effects. Laser photocoagulation has been demonstrated to be effective in the management of extrafoveal and juxta-foveal membranes of various aetiologies.[24][25][26][27][28][29][30][31] The Macular Photocoagulation Study[32][33][34] and other investigators[35],[36] have demonstrated a marginal benefit of laser treatment compared with observation, in certain eyes with ARMD, even when the neovascular tissue lies beneath the centre of the fovea. One of the principal limitations of laser photocoagulation is the concomitant damage to overlying neurosensory retina.[37] This is particularly harmful when the membrane is under the centre of the fovea because central vision is almost always significantly reduced after treatment.[33],[34],[38]

Surgical removal is an alternative means of eradicating subfoveal CNV with potentially less damage to neurosensory retina and better visual function. In 1988, de Juan and Machemer[39] reported 4 cases of submacular scar removal, using large circumferential retinotomy on the temporal side of the macula, allowing direct access and dissection of the submacular tissue. Because of a high incidence of proliferative vitreoretinopathy and retinal detachment, as well as discouraging visual results, this technique was not widely employed. Blinder et al[40] proposed a similar technique creating large flap retinotomies, modified by the preoperative administration of barrier photocoagulation treatment. Understanding the importance of subfoveal retinal pigment epithelium (RPE) integrity following subfoveal scar removal, they combined their technique with transposition of RPE flaps and homologous RPE grafts with limited success.[41]

In 1991, Thomas and Kaplan[42] reported a different approach to subfoveal neovascular membrane removal in POHS. The technique emphasized making small retinotomy away from the centre of the fovea; through this incision, the subfoveal neovascular complex was accessed and removed. The surgical technique has been established.[43][44][45][46][47][48][49][50] Emphasis has been placed on the design and development of smaller gauge instrumentation to facilitate subretinal tissue manipulation while minimizing RPE and photoreceptor trauma. However, the principal limitations of the technique arise from the frequent destruction of ocular architecture associated with the CNV, especially in ARMD. Hence, case selection is of critical importance.


  Case Selection Top


As with any new technique the determination of appropriate case selection awaits the outcome of randomized, prospective clinical trial which is currently underway. Choroidal neovascular membranes anterior to the RPE probably have the best surgical prognosis, as preservation of the RPE is a critical factor in the subsequent recovery of central vision. Surgical removal of subfoveal choroidal neovascular membrane is advised if it appears to lie anterior to the RPE. Contact lens examination of the macula and 2x colour-stereo views and stereoscopic fluorescein angiography helps in determining the location of the membrane. Clinical and angiographic findings which may suggest an anterior location of the neovascular membrane are summarized in [Table - 1] [Table - 2] respectively. Membranes posterior to the RPE tend to have clinical and angiographic findings that are reverse of t

hose for anterior membranes.


  Instrumentation Top


Thomas et al[51] developed instruments that facilitated this surgery as well as removal of submacular haemorrhage. Subsequently, Thomas and Ibanez[52] developed newer generation of subretinal instruments. These instruments are summarized in [Table - 3].


  Surgical technique Top


Current surgical technique is most effective in those cases in which the membrane lies predominantly anterior to the RPE. Thus, it can be removed without extracting large areas of RPE.

A standard three-port pars plana vitrectomy is performed. The placement of sclerotomy is extremely critical. The surgeon should decide preoperatively where the retinotomy is to be placed to avoid damaging major vessels, to provide adequate access to the subretinal membrane and to minimize the size of the scotoma. These factors usually dictate that the retinotomy be created in a straight temporal location and thus the superotemporal sclerotomy should be made near the horizontal meridian. If a sewn-on ring system is used to hold a corneal contact lens, it is sometimes advantageous to rotate the fixation flanges superotemporally and inferonasally from the horizontal to allow a nearly horizontal placement of the temporal port. A sclerotomy placed directly in the horizontal meridian allows a retinotomy to be made inferior to the fovea or papillo-macular bundle, in selected cases.

Although there is no data to support the importance of removing the posterior hyaloid face, its removal is attempted in every case. A silicone-tipped extrusion cannula is used to engage the cortical vitreous near the optic disc using active aspiration of approximately 150 to 300 mm Hg. A "fish strike sign,"[53] "divining rod sign"[54] or the absence of dripping into the collection chamber indicates that the posterior hyaloid has been engaged. The hyaloid can then be separated from the retina by gentle tangential and anteroposterior traction. Occasionally, a wave of separation is seen across the macula. In other instances, a Weiss ring is seen in mid vitreous cavity. An excellent technique involves the use of the subretinal pick which is used to engage the hyaloid at the optic disc margin and pull up the Weiss ring. This technique is employed if the silicone tip fails to detach the hyaloid quickly. The separated posterior hyaloid is cut and aspirated to the equator with the vitrectomy probe.

The placement of retinotomy takes into account of the following facts : (1) the exact location and extent of the membrane under the fovea; (2) the presence of presumed adhesions between the neurosensory retina and underlying tissue; (3) the dimensions of the subretinal instruments; and (4) the topographic anatomy of the neurosensory retina and nerve fiber layer. In most cases, these factors dictate a straight temporal or slightly superotemporal location for the retinotomy. However, a retinotomy may be created superonasal to the fovea. With newer 33- and 36-gauge instruments, the retinotomies are small enough that there is no significant damage to the papillomacular bundle. Besides being in the most advantageous location, the retinotomy should be as small as possible. A 120-degree angled, sharply pointed 36-gauge subretinal pick is used to pierce undiathermized neurosensory retina. While intraocular pressure is raised, the tip can be pushed through neurosensory retina to achieve a very tiny retinotomy. As the pick is obliquely advanced through the neurosensory retina, transient blanching of the choriocapillaris may be seen. Rarely, the local RPE underlying the retinotomy site may be scraped as the pick enters the subretinal space. However, this can be avoided by gently lifting the pick as the retina is perforated. A small haemorrhage may occur as retinal capillaries are cut, but this always responds to the increased intraocular pressure and is limited.

After retinotomy, an angled 33-gauge infusion cannula is introduced beneath the retina and balanced salt solution is infused to elevate the neurosensory retina [Figure - 1]. This is accomplished by pushing on the plunger of a syringe that is connected to the hub of the needle by a short piece of tubing. To avoid trapping air bubbles within the tip, balanced salt solution is gently infused as the instrument is entered into the eye and before entering the subretinal space. Slow infusion is very important as this step may lead to the development of a retinal break, especially in areas of strong chorioretinal adhesions. Excessive infusion pressure could also tear the retina. As the fluid enters the subretinal space, attention is directed to edges of the laser scars and/or adhesions to the underlying membrane. A neurosensory detachment can be created or enhanced by injecting balanced salt solution with the help of a controlled infusion pump.[55]

The subretinal membrane is dislodged with the aid of the pointed subretinal pick [Figure - 2]. The sharp end of the pick is very helpful in engaging the edges of the neovascular complex and facilitating its separation from the underlying RPE. The pick is moved in a pivoting or rotating manner to avoid stretching or enlarging the retinotomy. In most cases, the neovascular complex dislodges easily from the underlying subfoveal RPE. However, it remains attached to the edge of a laser scar or to the stalk of choroidal vascular ingrowth. Occasionally, horizontal subretinal scissors are required to cut firm adhesions. If the retina is not mobilized over the entire photocoagulation scar, separation is achieved at least far enough into the scar to allow manipulation and extraction of the membrane without tearing adjacent retina. Trauma to foveal photoreceptors from either the pick or scissors is avoided.

A positive action horizontal forceps is introduced (closed) through the retinotomy, which has usually enlarged during the subretinal manipulation. The opened blades are placed around the stalk or the adhesion, with the membrane in front of the blades. Gentle traction with the blades held closed, breaks the connection [Figure - 3]. If traction on the retina is seen, the membrane is released and further separation of the complex from neurosensory retina is accomplished. If excessive tugging and displacement of RPE is seen, then consideration is given to using the subretinal scissors to cut the membrane rather than breaking it with the forceps. When the vascular connection from the choroid is about to be severed, the intraocular pressure is raised to approximately 80 mm Hg. Minimal haemorrhage is often encountered when the membrane is removed. The intraocular pressure is elevated for at least one minute and any evidence of rebleeding is observed while the pressure is slowly lowered. If these measures fail, hemostasis may be achieved by subretinal endophotocoagulation. Essentially all membranes are easily grasped with horizontal subretinal forceps. Vertical action forceps may be used in extracting relatively thin discs of neovascularization that have been disconnected from the choroid. Once hemostasis is achieved, the membrane is extracted through the sclerotomy. A large membrane is divided with an intraocular scissors. Scleral plugs are placed and retina is inspected with indirect ophthalmoscope and scleral depression to verify that no peripheral tears have occurred. A complete fluid-air exchange is performed. Standard extrusion needles or silicone tipped needles are used with the aspirating tip over the optic nerve. Leaving the air in the vitreous cavity for a few minutes allows some of the residual subretinal fluid to come through the retinotomy, where it can be aspirated. Balanced salt solution is gently reinfused over the optic nerve after the vitreous cavity has been dry for a few minutes. The eye is completely filled with fluid and face down positioning is advised for 12 to 18 hours.


  Sample Cases Top


Case 1: Presumed Ocular Histoplasmosis Syndrome

An 82 year-old male had developed a fibrotic disciform scar in the left eye three years before presentation. He developed choroidal neovascularization in the right eye for which he underwent photocoagulation twice. Recurrent neovascular tissue arose predominantly superior to the fovea, and best corrected visual acuity dropped to 2/300. Given the clinical appearance of the lesion (well-defined borders with blood apparently outlining a cleavage plane between the recurrent membrane and underlying retinal pigment epithelium), the referring retinal specialist felt that surgical removal of the complex might be preferable to additional laser. Indeed during surgery, the membrane peeled up from underlying retinal pigment epithelium and came out in one piece with the prior laser scar. Within three months, visual acuity had improved to 6/12. [Figure - 4]-[Figure - 7]

Case 2: Age-Related Macular Degeneration

A 57 year-old male presented with some drusen and pigment disturbance in both eyes, and an occult choroidal neovascular process was juxtafoveal in location in the right eye. He underwent laser photocoagulation; despite, he developed a subfoveolar recurrence. Best corrected visual acuity was 6/120 prior to surgery. During the vitrectomy, the recurrent neovascular complex could be reflected from the underlying foveal RPE, and the entire complex was removed. Postoperatively, a hyperpigmented reaction in the central RPE developed with a dark black appearance. Visual acuity improved to 6/6 and has remained at this level with four years follow-up. [Figure - 8] [Figure - 9]


  Complications Top


Complications[56] which might be encountered in submacular surgery are summerized shown in [Table - 4].


  Postoperative Management Top


Patients are examined at 24 hours and at 1 week after surgery for signs of infection, retinal detachment or elevated intraocular pressure. The view is usually adequate immediately for the presence or absence of subfoveal RPE. Occasionally, residual subretinal blood will obscure the underlying tissues for a longer period of time. Fluorescein angiography is repeated as soon as the media clarity allows to establish a new baseline for monitoring recurrence. Not uncommonly, the site of the original choroidal ingrowth stalk may demonstrate recurrence. Often this site is not subfoveal and therefore slit lamp laser photocoagulation can be employed to ablate the recurrence. Since the membranes recur in approximately one third of cases within 6 months, close follow-up is essential.


  Adjuncts to surgery Top


Subretinal endophotocoagulation

Transretinal laser photocoagulation invariably damages the underlying RPE and the overlying neurosensory retina, thus minimizing the prospect for visual function in the treated site.[57],[58] Selected delivery of laser energy within the subretinal space could theoretically allow for the obliteration of a subretinal choroidal neovascular complex and reduce damage to the overlying photoreceptor layer. Subretinal endophotocoagulation in rabbits has shown that low to moderate intensity burns preserve the overlying retina and high laser energy powers will cause coagulative necrosis of the outer retinal layers.[59] Thomas and Ibanez[60] developed a subretinal laser delivery system as an adjunct to the surgical excision of subfoveal choroidal neovascular membranes. A 31-gauge subretinal endolaser probe is used; it takes advantage of the difference in the index of refraction between silica and balance salt solution to produce a down and forward laser beam. Strong unrelenting adhesions to previous laser or inflammatory chorioretinal scars occasionally preclude safe excision of a neovascular complex. When this situation is encountered, the firm adhesion or stalk of neovascular ingrowth can be cut with subretinal scissors and photocoagulated (outside the fovea) with the subretinal endolaser probe, minimizing damage to subfoveal RPE, choriocapillaris and the overlying neurosensory retina. In other instances, a small subfoveal neovascular complex anterior to the RPE is found intraoperatively to have a larger sub-RPE component, the excision of which may lead to the development of a large RPE tear. In these cases, the anterior component of the neovascular complex can be reflected and photocoagulated in an extrafoveal location. Subretinal endophotocoagulation also allows for the obliteration of a bleeding subretinal stump that has failed to respond to elevated intraocular pressure.

Interferon Alfa-2a

Interferon alfa-2a (INF-2a) is an endogenous glycoprotein with antiproliferative, immunoregulatory, antiviral and antiangiogenic properties[61][62][63][64][65][66] and has been reported to be beneficial in the treatment of subretinal neovascularization[67],[68] The early experience of Thomas and Ibanez[69] have been disappointing. In a prospective study, patients with recurrent subfoveal neovascularization following surgical excision and patients with subfoveal choroidal neovascularization without previous surgical excision received INF-2a in a dose 3.0 to 6.0 million units /meter2 body surface area, every other night for an average of 12 weeks. Use of INF-2a did not improve visual acuity or fluorescein angiographic appearance of subfoveal neovascular membranes in 90% of cases and was associated with significant side effects including fever, alopecia, leukopenia, thrombocytopenia, elevated liver enzymes and suicidal tendencies. Recently, Chan and associates[70] reported an efficacy and toxicity study on the treatment of choroidal neovascular membranes by INF-2a. The regression of choroidal neovascularization was minimal. Toxic effects interfering with patients' performance status were associated with the treatment. It is possible that higher doses may achieve a therapeutic response. Better drug delivery systems, in future, may allow for the selective intraocular administration of high doses, thus bypassing its toxicity. Unfortunately, multinational, randomized, prospective study organized by Hoffman-LaRoche has revealed no treatment benefit (David Guyer, personal communication).

Tissue Plasminogen Activator

Tissue plasminogen activator (t-PA) is a fibrinolytic agent[71] that activates plasminogen specifically in the presence of fibrin and whose activity is enhanced in the presence of fibrin.[72] Thomas, Lopez and Lambert[73] used t-PA as an adjunct to the surgical removal of subfoveal choroidal neovascular membranes. t-PA was used at a concentration of 6 ug/0.1 cc. t-PA was injected into the subretinal space, 30-40 minutes were allowed to elapse for fibrin break down. t-PA dissolved the fibrin rim surrounding recent subfoveal membranes but was less effective on more mature lesions. They believe that enzymatic dissolution of the fibrin rim resulted in less shearing being applied to the surrounding photoreceptors and RPE when more recent subretinal neovascular membranes were grasped and removed. In contrast, with older membranes, the pseudopod-like strands of mature organized fibrin were more adherent and more manipulation was required for membrane removal, with resultant increased risk of photoreceptor shearing and RPE damage. No increased bleeding occurred in these patients when the membranes were removed. They believe that t-PA may be an useful intraoperative tool to limit the damage to surrounding structures during surgical excision of recent subfoveal choroidal neovascular membranes with surrounding fibrin rims. In our experience, mechanical pressure against the edge of the neovascular complex usually peels up the fibrin rim, unless the complex has grown beneath the RPE.

Liquid perfluorocarbons

Lambert et al[74] used Perfluoro-N-octane to assist in the evacuation of subretinal haemorrhage and fluid and to facilitate endophotocoagulation of the retinotomy site. Perfluoro-N-octane was injected after membrane removal, to reattach the retina and tamponade possible bleeding. An fluid-air exchange with removal of the perfluoro-N-octane was performed before closure of sclerotomy. In our experience, simple fluid-air exchange appears to achieve the same result.


  Results Top


Thomas and Kaplan[43] treated two patients of POHS with subfoveal neovascular membranes and progressive visual acuity loss to 6/120. Visual acuity returned to 6/6 with seven months of follow-up in one patient and to 6/12 with three months follow-up in the other. Lambert et al[74] reported the results of surgical excision of ten consecutive subfoveal choroidal neovascular membranes in patients with ARMD. Six of the ten patients showed visual improvement at one-month and three-month follow-up. Thomas et al[75] reported surgical management of subfoveal choroidal neovascularization in 33 eyes with ARMD, 20 eyes with POHS and 5 eyes with miscellaneous aetiologies. Five eyes also received subfoveal RPE patches. With limited follow-up, significant improvement in vision (defined as 2 Snellen lines) was achieved in 7 of 22 eyes with ARMD CNV removal, 0 of 4 eyes with ARMD CNV removal and RPE patches and 1 of 7 eyes with ARMD CNV disconnection. Significant improvement was achieved in 6 of 16 eyes with POHS removal and 0 of 4 eyes with POHS CNV disconnection. In 5 eyes with miscellaneous CNV, 2 eyes improved. CNV recurred in 29 %. Berger and Kaplan[76] reported their series of 15 patients with POHS and 19 patients with ARMD followed for an average of 4 months postoperatively. Snellen visual acuity improved by 2 lines or more in 8 of 15 (53 %) cases of POHS while 14 of 19 (74 %) cases of ARMD showed either slight improvement or stabilization of their vision. CNV recurred in 2 of 15 (13 %) and 3 of 19 (16 %) eyes with POHS and ARMD, respectively.

Thomas et a,[77] updated their surgical results and explored correlation between preoperative characteristics and final postoperative visual acuity in 67 eyes with POHS, 41 eyes with ARMD, 10 eyes with myopia, 9 eyes with multifocal choroiditis, 8 eyes with idiopathic CNV, 4 eyes with angioid streaks and 8 eyes with miscellaneous aetiologies for CNV. In eyes with POHS, mean follow-up was 10.5 months. Visual acuity was stable or improved in 56 (83 %) eyes and 6/12 or greater in 21 (31 %) eyes. Mean interval to best visual acuity was 3 months. In eyes with ARMD, mean follow-up was 15 months. Visual acuity improved in 5 (12 %) eyes and was 6/12 or greater in two (5 %) eyes. The interval to best visual acuity was 5 months. A recurrence rate of 37% (ARMD) and 27% (POHS) had no statistically significant effect on final visual outcome. Patients with focal disorders of the RPE-Bruch's membrane complex appear to have a better surgical outcome than those with diffuse disease.

Adelberg et al,[55] in their retrospective analysis of surgical removal of CNV in myopia, angioid streaks and other disorders, found visual acuity to be stable in 10 of 17 (59 %) eyes, improved by 2 or more Snellen lines in 6 (35 %) eyes and decreased in 1 (6 %) eye. Postoperative visual acuity better than 6/24 was achieved in a minority of eyes. CNV recurred in 2 eyes. Ormerod et al[78] reported long-term outcomes after the surgical removal of advanced neovascular membranes in ARMD. The mean choroidal neovascular membrane size was 7 disc diameters. Surgically induced mean RPE defect was 14 standard areas in size. Eight of ten patients improved one to two lines of Snellen's visual acuity postoperatively. A 2-year recurrence rate of 40% was observed. O'Connor et al[79] surgically removed a large extrafoveal (predominantly peripapillary) fibrotic choroidal neovascular membrane in a patient with ARMD. Visual acuity improved from 6/60 to 6/9.

Considerations regarding the feasibility of surgical excision of subfoveal neovascular membranes:

Surgical excision of subfoveal neovascular membranes may result in recovery of excellent visual acuity in patients with POHS but not in patients with ARMD. Gass[80] provided histopathological evidence from autopsy eyes to propose a classification scheme. In type 1 CNV, as typically seen in individuals older than 50 years with ARMD, a broad flat plate of CNV insinuates itself beneath native RPE and Bruch's membrane. In type 2 CNV, typically seen in younger individuals with POHS, a focus of CNV penetrates the RPE focally, grows out from a stalk and is surrounded over time by "reactive" RPE. Surgical excision of this membrane permits reapproximation of the retinal receptors and native pigment epithelium and may be associated with remarkable return of visual acuity.

Experimental aspects of retinal pigment epithelium transplantation:

Increasing attention has been focused on the problem of transplanting RPE onto Bruch's membrane, within the last decade.[81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97] Experiments have been performed in the non-human primate to address the questions concerning repopulation of retinal pigment epithelial cells in situ and photoreceptor repair after submacular surgery.[98] Subretinal fluid injection led to shortening of outer segments and occasional separation of RPE cells from Bruch's membrane, with no visible damage to the choriocapillaris.[99] The photoreceptor regained their normal length by 9 months after the surgical procedure. The regeneration of RPE was observed only if Bruch's membrane was intact. Repopulation of retinal pigment epithelium in the adult primate could occur rapidly and could support the repair of damaged photoreceptors following submacular surgery.[98] Morphological effects of surgical debridement of RPE were also studied in the domestic pig.[100] The choriocapillaris was found to be intact in areas of Bruch's membrane that were repopulated by hypopigmented RPE. Clinically, there is a high correlation between areas of RPE drop out in atrophic age-related macular degeneration and corresponding areas of atrophy of the choriocapillaris in humans.[101][102][103][104] Atrophy of the choriocapillaris may also occur after the excision of choroidal neovascular membrane in humans.[105][106][107][108] If the RPE is removed or damaged during surgical excision of subfoveal neovascularization, it is unlikely to heal in the elderly human because senescent RPE has a limited ability to regenerate, as demonstrated in tissue culture in comparison to young RPE.[109] In addition, it is likely that the integrity of the underlying substrate is important for healing and determining the morphologic features of the RPE monolayer[110][111][112] and the RPE may not heal on the diseased Bruch's membrane after subfoveal surgery in elderly humans.

Future advances in the surgical management of choroidal neovascular membranes may require stimulation of adjacent RPE growth factors to enhance RPE regeneration beneath the fovea.[113],[114] Alternatively, the development of rapidly emerging technologies such as RPE and photoreceptor transplantation,[113][114][115] may improve the visual prognosis after surgery in these patients. Any new era will probably see the use of pharmacological agents, retinal transplantation, and gene therapy to achieve therapeutic success.[114]


  II. SUBMACULAR HAEMORRHAGE Top


Blood beneath the neurosensory retina almost always originates from the choroidal circulation. Trauma to choroidal vessels can produce haemorrhage. Blunt or penetrating trauma and inadvertent surgical trauma with a deep suture during scleral buckling or during drainage of subretinal fluid either internally or externally may result in choroidal rupture.[116],[117] In absence of trauma, haemorrhage can occur secondary to choroidal neovascularization. Small haemorrhages frequently accompany ingrowth of vessels from the choroid. Extensive haemorrhages are believed to occur due to rupture of large choroidal vessels that extend into disciform scars.[75],[118] Vessels in disciform scars have been observed to have arterial and venous characteristics and are continuous with choroidal arteries and veins, respectively.[119] Leakage of blood or serous fluid from the neovascular tissue leads to detachment of the RPE and produces pressure on the artery and vein as they enter the fibrovascular scar. This pressure reportedly leads to necrosis of the artery and, when it ruptures, massive haemorrhage occurs with accumulation of blood under the RPE, under neurosensory retina and in some cases in the vitreous cavity.[119]


  Mechanism of Retinal damage Top


Subretinal blood is toxic to the outer retina and has been documented to cause irreversible photoreceptor damage.[120],[121] Laboratory animal studies have shown that the degree of retinal destruction is correlated with the duration of contact of the retina with blood. These animal studies show that damage can occur as early as 1 hour[122] with moderate to severe outer retinal destruction at 3 to 7 days and full thickness retinal degeneration by day 14.[120],[123],[124] Subretinal blood clots form a mechanical barrier between the retina and the RPE. This inhibits metabolic exchange between retina and RPE.[120] Retinal toxicity results from iron liberated from haemoglobin that is released from degenerating erythrocytes.[121] Glatt and Machemer[120] showed that subretinal blood clot adherence and retraction caused fractional forces on the photoreceptors, which led to outer retinal damage. The role of fibrin in causing retinal damage associated with subretinal haemorrhage was better defined by Toth et al.[122] They suggested that a fibrinolytic agent be used to dissolve the fibrin meshwork, thereby preventing the shearing effect on the photoreceptors. Benner et al[125] demonstrated that t-PA could be safely used in the subretinal space at concentrations of 2.5 to 200 mg/liter. Higher doses caused severe, irreversible toxic effects to the photoreceptor-RPE complex. The toxic effects of tPA were attributable to the carrier vehicle. Coll et al[126] reported the effect of intravitreal t-PA on experimental subretinal haemorrhage. Intravitreal t-PA, 1 day after subretinal injection of blood in rabbits facilitated more rapid lysis of clotted blood, however, retinal damage was not prevented.


  Natural History Top


The visual acuity outcome of subretinal haemorrhages varies depending on the extent, location and thickness of the haemorrhage.[127] Gillies and Lahav[128] reported 3 patients with ARMD, myopia and trauma with neither thick nor large subretinal haemorrhages. Their initial visual acuities of counting fingers (2 eyes) and 6/120 improved to 6/12 in 6 months, 6/9 in 3 months and 6/18 in 6 months, respectively. Bennett et al[116] reviewed 29 patients with large subfoveal haemorrhages followed for an average of 3 years. Thicker haemorrhages had poorer final visual acuity than did thinner haemorrhages. Eyes with ARMD had a worse final visual acuity than non-ARMD eyes. Eyes with choroidal rupture faired better than other eyes. The presence of ARMD, rather than the thickness of the haemorrhage was the factor most predictive of poor outcome. Fekrat et al[129] reviewed the natural history of 41 eyes with submacular haemorrhages and found a trend toward declining visual acuity over time. The median overall change between the initial and 3-year visual acuities was a loss of four lines. Eyes with larger and thicker haemorrhages had poorer,visual acuity outcomes.


  Management Top


In 1983, Dellaporta,[130] described passing an endodiathermy needle through retina, choroid and sclera in a patient with a 10-week history of massive posterior pole subretinal haemorrhage and a visual acuity of 3/200. The cauterized hole in the retina allowed the blood to spill into the vitreous cavity and vision returned to 6/9. Hanscom and Diddie[131] first used modern vitrectomy techniques, internal retinotomy, endodrainage of blood and fluid-air exchange in the management of submacular haemorrhage. De Juan and Machemer[39] used vitrectomy and a combination of drainage and irrigation of subretinal clot and disciform scar removal. Early surgical intervention to avoid toxicity from subretinal haemorrhage was stressed by Slusher.[132]


  Case Selection Top


Multiple preoperative, intraoperative and postoperative factors have an impact on the visual result following surgery. Preoperative factors, including the baseline health of the neurosensory retina and submacular RPE, the presence of choroidal neovascularization or disciform scarring or previous foveal photocoagulation will determine the postoperative visual potential. The health status of the RPE and neurosensory retina may also influence the tolerance of these tissues to the noxious effects of subretinal blood. Eyes with ARMD may have more extensive and diffuse photoreceptor /RPE dysfunction and less metabolic reserve than eyes without ARMD (ie, eyes with choroidal neovascular membranes owing to POHS, macroaneurysm, angioid streaks or idiopathic causes). This may partially explain why eyes without ARMD are more likely to have visual improvement following surgery than eyes with ARMD. The duration of submacular haemorrhage may also be an important factor. Progressive photoreceptor destruction has been observed to occur for up to 14 days following induction of experimental subretinal haemorrhage. Postoperative visual function may also be affected by photoreceptor and/or RPE trauma induced by surgical manipulations in the subretinal space as well as intraoperative and postoperative complications.

In the absence of results from clinical trials, case selection remains unclear. The randomized, prospective Submacular Surgery Trial will compare surgical removal of large submacular haemorrhage secondary to ARMD. No randomization trials have been proposed for haematomas of other aetiologies. Hence, at the present time impressions regarding case selection can be offered. Relatively thin haemorrhages unassociated with CNV often do well with observation. Thick haemorrhage without known CNV may be appropriate for removal. Thick haemorrhages with probable CNV (typically from CNV) remain controversial. Recent onset haemorrhages probably have a better surgical outlook than do older haemorrhages and may be appropriate for t-PA use.


  Surgical technique Top


Following a pars plana vitrectomy with removal of the posterior hyaloid, a retinotomy site is created adjacent to the clot with the use of intraocular diathermy. The retina is elevated from the subretinal blood by gentle infusion of balanced salt solution through the retinotomy site. If the blood clot was large, the retinotomy is enlarged in a controlled fashion along the horizontal raphe with the use of vertical cutting vitreoretinal scissors. A silicone-tip extrusion needle is placed through the retinotomy and any liquid blood is gently aspirated. The silicone tip is then used to engage clotted blood and clot extraction is attempted with the use of extrusion needle and high suction pressure. If this is unsuccessful, vitreoretinal forceps are placed through the retinotomy and used to extract the clot mechanically. During clot removal, the intraocular pressure is increased to decrease the chances of additional subretinal bleeding. The intraocular pressure is then gradually decreased. Residual liquid subretinal bleeding is aspirated and a fluid-air exchange is performed to flatten the retinotomy. Prone positioning throughout the first postoperative week is advised.

t-PA can be used as an adjunct to surgery. Following small retinotomy, 10 ug/ 0.1 ml of recombinant tPA is injected into the submacular clot. After a waiting period ranging from 20 to 40 minutes, the haemorrhage is drained with either a Lewis double-lumen subretinal irrigator-aspirator or a single 30-gauge subretinal cannula through the retinotomy site. Additional injections of t-PA (10ug/ 0.1 ml) is performed with the aspirating tip over the retinotomy site to remove any residual subretinal blood. Kimura et al[133] have reported removal of subretinal haemorrhage facilitated by preoperative intravitreal t-PA. Six meg (0.1 ml) of t-PA is injected, 12 to 36 hours prior to surgery, slowly into the mid vitreous cavity through the pars plana with either a topical or retrobulbar anesthesia. A standard 3-port pars plana vitrectomy is performed and an attempt is made to simply aspirate the liquified haemorrhage with a soft tipped cannula. If this is not completely successful, a balanced salt solution can be instilled subretinally to elevate the retina and the aspiration is repeated.


  Sample Case Top


Case 3: Submacular Haemorrhage

A 69 year-old woman presented with a two day history of sudden loss of vision in the left eye. She had a known history of age-related macular degeneration and a serous pigment epithelial detachment in the right eye. Her left eye was found to have a thick submacular haemorrhage extending from the superotemporal to inferotemporal arcade. At the time of surgery, 0.3 cc of 10 mcg/0.1 cc tissue plasminogen activator was infused into the subretinal space, and 25 minutes was allowed to elapse. t-PA and free subretinal blood was actively aspirated from the subretinal space. A large clot/ subretinal neovascular membrane complex was removed with subretinal forceps. Postoperatively, vision remained at 6/60 due to the loss of subfoveal RPE [Figure - 10] [Figure - 11].


  Results Top


Hanscom and Diddie[131] reported evacuation of subretinal haemorrhage of 1 week duration from two patients (ARMD and a ruptured macroaneurysm). Visual acuity improved from counting fingers to hand motions to 6/120 by 3 months and 6/24 at 1 month, respectively. DeJuan and Machemer[39] obtained improved, though limited, visual acuity in three of their four patients with exudative ARMD and large submacular haemorrhage. These patients had subretinal haemorrhage for greater than one week duration. Wade et al[117] evacuated subretinal haemorrhage greater than 5 disc diameters in 14 patients. Five patients had massive subretinal haemorrhages associated with ARMD. The other nine patients had haemorrhagic retinal detachments, scleral buckling complications leading to subretinal haemorrhage, traumatic retinal detachments and sickle cell disease. All five ARMD eyes had preoperative visual acuities of 6/60 or worse and postoperative visual acuities of 5/200 or less. Three other eyes had improved visual acuity postoperatively. ARMD was associated with guarded visual recovery of visual acuity. Vander et al,[134] in 11 patients, showed improved visual acuity in 4 (36%) who underwent evacuation of the subretinal blood. However, retinal detachments with PVR developed postoperatively in 36% of patients and cataracts developed postoperatively in another 36%.

Peyman et al[135] reported t-PA assisted removal of subretinal haemorrhage. One (33 %) of three eyes had improved visual acuity and the other two eyes were stabilized. In the series of Lewis,[136] twenty (83 %) of 24 eyes showed an improvement in visual acuity. Eight eyes (33 %) had postoperative visual acuity of 6/60 or better. In the series of Lim et al,[137] 5 (28 %) of 18 eyes showed an improved visual acuity of two lines or more. The use of perfluorooctane showed a trend toward better postoperative visual acuity outcomes. The perfluorooctane served to tamponade the retinotomy site and keep the t-PA in the subretinal space during the waiting period. The subsequent use of perfluorooctane to express blood from the subretinal space may limit the manipulation required and thus spare the underlying retinal pigment epithelium and the overlying retina from mechanical trauma and cellular loss. Ibanez et al,[138] in their 47 cases of submacular haemorrhage removal, noted that ARMD eyes had a poor overall progress with or without use of t-PA. Recently, Kamei et al[139] reported surgical removal of submacular haemorrhage using t-PA and perfluorocarbon liquid. Best-corrected final visual acuity improved postoperatively in 18 (82%) of the 22 eyes.


  Complications Top


Substantial postoperative complications have been seen following surgical removal of subretinal haemorrhage. Postoperative retinal detachment, recurrent subretinal haemorrhage, subretinal fibrosis and optic atrophy may occur.


  The Submacular Surgery Trial Top


The safety and possible efficacy of submacular surgery has been questioned.[140],[141] It is appropriate to proceed with a randomized, controlled, prospective multicenter clinical trial to further evaluate subfoveal surgery.[142],[143] The Submacular Surgery Trial[144] will evaluate surgery in four categories: Group 1 will include eyes with ARMD and subfoveal choroidal neovascular membranes in which the benefit of laser photocoagulation was minimal. Randomization will be between surgery and observation. Group 2 will include eyes with ARMD and subfoveal choroidal neovascular membranes that are deemed eligible for photocoagulation according to the Foveal Photocoagulation Study. Randomization will be between surgery and laser photocoagulation. Group 3 will include eyes with ARMD in which submacular haemorrhage comprises more than 50% of the macular lesion. Randomization will be between surgery and observation. Group 4 will include eyes with POHS and those with idiopathic and subfoveal CNV. Randomization will be between surgery and observation. By carefully following the prospective protocol established in this trial, data will be collected that will help define the appropriate role of submacular surgery in the management of patients with these difficult problems.

 
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    Figures

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Natural History
Management
Case Selection
Instrumentation
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Sample Cases
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Adjuncts to surgery
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Natural History
Management
Case Selection
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