Ординатура / Офтальмология / Английские материалы / Retinal and Vitreoretinal Diseases and Surgery_Boyd, Cortez, Sabates_2010

As in other pathologies, it is probable that the passage of new vessels from the choriocapillaris into the subretinal space is permitted by the ruptures found in Bruch’s membrane associated with choroidal ruptures. Nevertheless, a biochemical theory has been postulated, with the stimulation for neovascularization originating in the RPE or in the neurosensory retina.(17,18)

There are mainly three causes that can provoke diminution of visual acuity in

choroidal ruptures: extension of the rupture that involves the fovea (Figure 3), presence of choroidal neovascularization, and blood accumulation in the subretinal space and sub-RPE (Figure 4). Associated choroidal neovascularization can appear months or years later following trauma(19) and could be associated with serous or hemorrhagic retinal detachment. Successful argon laser treatment of this neovascularization has been reported.

Visual acuity loss secondary to choroidal ruptures can also be explained by a posttraumatic pigmentary retinopathy.

In 1980 Hart(20) reported campimetric findings associated with choroidal ruptures. He observed central scotomas that gradually showed improvement of sensitivity after weeks or months following the trauma. Nevertheless some cases presented field defects apparently located in areas far from the choroidal rupture and presumptively due to post-traumatic pigmentary retinopathy. Similar data were found in a study that we made using the Rodenstock Scanning Laser Ophthalmoscope.(21) We detected the presence of absolute scotomas at the site of the choroidal rupture in 80% of cases. The extension of the scotomas was larger than the choroidal defects in 30% of cases. These findings could explain why some patients who do not show compromise of the fovea by choroidal rupture can present a visual acuity impairment.

Toxicity of Subretinal Blood

It has been documented that blood localized in the subretinal space is toxic and provokes irreversible damage to photoreceptors after 24 hours. In studies made in rabbits, Glatt and Machemer(22) demonstrated that blood produces damage to photoreceptors and the internal nuclear layer 24 hours after experimentally injecting blood into the subretinal space. They felt that the probable causes of these alterations were due to a combination of mechanical damage to the external segment of the photoreceptors caused by clot contraction, toxicity by iron components, and the barrier of the clot.

Blood clots in this space form a mechanical barrier between the retina and the RPE. This produces a limitation in the metabolic exchange that is essential for the appropriate functioning of these structures. This kind of barrier also has been demonstrated in rabbits following silicone injection.(23)

Green and Key(24) demonstrated histopathologically in humans that there is loss of photoreceptors and thinning of external nuclear layer in cases with serohemorrhagic detachment of retina.

Some reports of subretinal hemorrhages describe a poor visual prognosis. In 1986 El Baba(10) reported 15 patients who presented subretinal or vitreous hemorrhage secondary to ARMD. Ten of these showed extensive subretinal hemorrhage. At the beginning, visual acuities were 20/400 or worse and subsequently in the follow up, it was determined that final visual acuity remained in hand movements or worse. Histopathological results showed likewise cellular damage of photoreceptors with diffuse cellular loss (Figure 5).

In 1991, Toth et al.,(25) reported similar changes in the retina of cats when experimentally injecting blood subretinally. Twenty-five minutes following the injection, interdigitated fibrin was observed in the photoreceptors. At one hour, fibrin layers were causing a total detachment of the external and internal segments of the photoreceptors. Fourteen days later, an extensive and severe destruction of external layers of the retina was observed. According to these histopathological findings, fibrin may be the causative agent of major

damage to photoreceptors by producing traction with subsequent rupture and separation.

The cleansing of blood from the subretinal space includes phagocytosis and fibrinolysis. Macrophages are present that phagocytize the hemorrhage and degenerate when migrating to the RPE. Müller cells and the RPE itself also phagocytize cellular detritus and transform hemosiderin to ferritin. This process can function well in small hemorrhages, but, when the hemorrhage is extensive, iron radicals are released due to a saturation of iron binding proteins. The free iron poisons the enzymatic intracellular functions. Koshibu(26), using albino and pigmented rats,

demonstrated macrophages surrounding the erythrocytes, after subretinal injection of autologous blood through the choroid. Some erythrocytes were surrounded by RPE cells that showed degenerative changes probably due to the toxic effect of the iron released by the process. Some of the ferritin particles in the RPE had migrated through Bruch’s membrane into the endothelial cells of the choriocapillaris.

Neurosensory retina showed extensive degenerative changes after 3 months. This cellular degeneration was similar to that found in cases of hemosiderosis bulbi and probably was due to the effect of free toxic iron and the metabolic alteration following

degeneration of the RPE, Müller cells and endothelial cells of the retinal capillaries.(27)

Therapeutic Possibilities

The management of subretinal hemorrhage depends mainly on what caused it, its location, and its extent. The choices include observation with no intervention, vitrectomy with mechanical extraction of the clot, and vitrectomy using fibrinolytic agents in order to achieve lysis of the clot. In general, we

can mention that every one of them has risks and advantages. That is why it is very important to judge the risk/benefit in order to decide on a surgical procedure.

In many cases, the hemorrhage is not extensive and is not thick, with a minimal elevation of the retina in the macular area (Figure 6). In these cases it may be convenient to observe the case because it is possible that a surgical procedure does not offer benefits and can be associated with intra and postoperative complications.

It is very important to determine what cases can be candidates for a surgical procedure of this kind, because there are cases that can have a satisfactory evolution with conservative treatment. In 1990, Bennett et al.(7) analyzed the factors that can participate in visual prognosis of subretinal hemorrhages secondary to different etiologies. Twenty nine cases were reviewed of which 7 presented hemorrhage secondary to trauma. After assessing the cause of the hemorrhage, the size, and thickness of it, it was determined that the hemorrhage diameter does not have a significant prognostic value. The hemorrhages of greater thickness showed a final visual acuity worse than those less thick. On the other hand, the ones secondary to ARMD had worse final visual acuity than the ones caused by other pathologies like choroidal ruptures. The most important predictive factor was the presence of ARMD more than the hemorrhage thickness itself (p=.03).

Hemorrhages secondary to trauma may compromise vision less as long as there is no underlying base pathology such as ARMD with atrophic areas of the RPE and choriocapillaris, with subretinal hemorrhages(28), and subretinal neovascularization. Nevertheless a choroidal rupture can directly affect visual acuity without foveal compromise.

Berrocal et al(29) retrospectively assessed cases of macular subretinal hemorrhage secondary to different pathologies. Of 31 patients studied, 20 presented hemorrhage secondary to ARMD, 2 from trauma, and the 9 remaining eyes secondary to other pathologies. Of the eyes that presented with ARMD, eight

(40%) of the 20 showed improvement of visual acuity (> 2 Snellen lines), six (30%) had a final visual acuity of 20/80 or better and three (15%) had visual acuity of 20/40 or better. In the group of patients not related to macular degeneration, five (45%) of the 11 showed vision improvement and five (45%) achieved a visual acuity of 20/40 or better. The average follow up time in the study was 29 months. Even though the number of patients was limited in this study, Berrocal et al. conclude that in general, patients that do not have associated subretinal neovascular membranes may have a better visual prognosis.

The base diagnosis in these cases is important in order to weigh the visual prognosis when surgical evacuation of subretinal blood is considered. Wade et al(30) and Vander et al(31), demonstrated that in cases treated by means of subretinal blood removal in patients with ARMD, there was not a good recovery of visual acuity.

In patients operated in the group of Vander, surgery was made on the first week of appearance of the hemorrhage associated symptoms. Visual acuity improved in 36% of the cases. These authors postulated that the low visual acuity recovery could be due to two factors: the probable damage in photoreceptors when extracting the blood clot with no fibrinolytic agents, and the degenerative changes of the base illness.

In attempting to improve the visual possibilities of patients with macular hemorrhage, some investigators have developed

new surgical techniques in order to evacuate subretinal hemorrhage associated with various pathologies.

In 1983, Dellaporta reported a case of massive subretinal hemorrhage in which he passed an endodiathermy needle through retina, choroid and sclera achieving the passage of blood to the vitreous cavity.(32) Final visual acuity improved from 3/200 to 20/25. Hanscom and Diddie(33) used modern techniques of vitrectomy making internal retinotomy, endodrainage and fluid-air exchange in order to evacuate the subretinal blood. Later, de Juan and Machemer(34) used vitrectomy techniques in 4 eyes with a diagnosis of macular subretinal hemorrhage. Three of the operated eyes, showed also subretinal scars that were removed at the same time. In this procedure, it was either necessary to use multiple fluid-air exchanges in order to achieve the evacuation and expression of the blood clot or to make extensive retinotomies in order to accomplish this. The visual acuity improved in 3 of the 4 eyes. Nevertheless, 2 eyes presented postoperative complications characterized by retinal detachment and associated proliferative vitreoretinopathy (PVR). This work showed that it was possible to evacuate blood from the subretinal space by means of vitrectomy and retinotomy.

In 1990, Wade et al (30) reported the surgical results of 14 patients with a diagnosis of macular hemorrhage. They divided patients in groups depending on the etiology of the hemorrhage. Nine were secondary to retinal detachment or complications of surgery and 5 to ARMD.

The blood removal was made by means of a single or multiple retinotomies and the blood was aspirated with an extrusion cannula. In some cases forceps were used in order to extract the clot. The preoperative visual acuities not associated to ARMD were from 1/200 or worse in 8 of the 9 patients and 2/200 or worse in the cases associated with macular degeneration. After surgery, 8 of the 9 eyes not related to macular degeneration showed an improvement of vision of 20/400 or better while in 3 of the 5 patients of the group with macular degeneration they showed slight improvement of the visual acuity, but none better than 5/200. Postoperative complications reported in the study included subretinal recurring bleeding in three eyes and subretinal massive fibrosis in two eyes. The authors concluded in their work that the bad visual acuity obtained in the group of patients with macular degeneration was due to the presence of pre-existent macular disciform degenerative process.

When surgery is considered, the evolution time of the hemorrhage must be taken into consideration.Rubsamenetal(35) havedescribed the usage of immediate pars plana vitrectomy for the drainage of massive subretinal blood due to complications of surgery for retinal detachment. In the reported cases, no fibrinolytic agents were used and in all of them, expandable gases were used at the end of surgery in order to achieve a tamponade of the lesions. In 7 of 9 eyes, final visual acuity was 20/80 or better. The authors reported little extension of the retinotomies due to the fresh clot at the moment of surgery and that the retina was mobile. The results of

the visual acuities in this report as well as in others, demonstrate that cases with AMD treated with surgery show worse results.

Dellaporta in 1994(36) made intense applications of argon laser over the retina that covered the dark blood in the subretinal space. The resulting hole allowed blood to pass to the vitreous cavity. After a month, visual acuity improved to 20/60.

Usefulness of Recombinant

Tissue Plasminogen Activator

Fibrin plays an important role in the retinal damage caused by subretinal hemorrhage. That is why several investigators have used fibrinolytic agents such as the recombinant tissue plasminogen activator (tPA) initially in animals and later in humans showing its usefulness in clot lysis. Lewis et al(37) proved the efficacy and safety of tPA in rabbit eyes when injected in the subretinal space in induced hemorrhages. There was a rapid clot clearance in eyes in which tPA was administered compared with the ones with saline. There were no toxic effects reported when using 25 μg/0.1 ml and 50 μg/0.1 ml concentrations.

explained by three factors: 1) lysis of fibrin located between the photoreceptors, 2) dilution of the toxic factors released by the lysed erythrocytes; and 3) reduction of the barrier effect caused by the blood clot limiting the

metabolism between photoreceptors and the RPE. The fibrin lysis between photoreceptors probably is the most important factor in the damage prevention because the balanced saline solution injection can also dilute toxic factors and reduce the barrier effect.(38)

The usefulness of tPA in the subretinal clot has been documented by other authors.(39,40,41) Coll et al(42) made a study in which trans-scleral autologous blood was injected in the subretinal space of 34 rabbits. Twenty hours later, tPA was injected in the posterior vitreous of 24 eyes and saline solution in 10 eyes as controls. Subretinal blood lysis was evaluated by ophthalmoscopy and retinal function was assessed by electroretinography. In the eyes in which tPA was injected, a disappearance of the formed clot was seen at the 24 hours, and all the blood disappeared after 6 days. On the contrary, in the group with saline solution, the clot did not show modifications at 24 hours or even 3 days later. The presence of blood in the subretinal space caused an important reduction in the electroretinogram amplitudes both in the tPA group and in the control group. With these results, the authors concluded that although tPA application made a rapid clot lysis, it could not prevent retinal damage registered by electroretinography. Similar results were reported by Ibanez et al in humans. They reported the surgical results of 47 patients who presented subretinal hemorrhage.(43) In this study, the authors concluded that tPA addition in order to achieve clot lysis appeared not to have improved in a significant way the final visual acuity of the patients.

Surgical Technique for Evacuating Subretinal Blood

A three-port pars-plana vitrectomy is made and the posterior vitreous cortex removed. A useful way to achieve this separation is by means of the use of a flexible silicone tip in order to aspirate and thereby grasp the posterior vitreous surrounding the optic disc. Once vitreous occludes the tip, the aspiration pressure can be increased to 400 mm/Hg and a delicate movement made to completely separate the cortex up to the equatorial zone (Figure 7).(44) Another technique that we commonly use is by means of a vitreous cutter, using an aspiration pressure of 200 mm/Hg directly over the optic disc. In this way, it is possible to engage the posterior vitreous and then to detach it from the retina up to the equator. Once separated it is removed with the vitreous cutter. Although at the present time there are no reports that clearly show the advantages of vitreous cortex removal in these cases, it is probable that it diminishes the risk of secondary rhegmatogenous retinal detachment and PVR.

Next, a small retinal penetration is made with a 33-gauge, bent, sharp subretinal cannula (Infinitech, Chesterfield, MO) at one of the margins of the hemorrhage. It is important not to make this cut over the clot because in case it cannot be completely extracted, the neurosensory retina will not lie in complete apposition with the RPE, and that can allow a secondary retinal detachment.(44) If that instrument is not available, an MVR blade

Figure 7: Removal of the posterior vitreous gel with a silicone-tipped extrusion needle with active suction. Bending of the silicone tip indicates that the tip is engaged in cortical vitreous.

can be used perfectly if the tip is bent approximately 3 mm (Figure 8). The angle of this bend will depend on the entrance site: if the hemorrhage is located in the posterior pole, it will be a 130-degree bend and if the hemorrhage is extended to more peripheral areas it must be bent to 90 degrees.

The retinal perforation is commonly made in the temporal side, but it can be made in the superior or inferior areas of the macula depending on the surgeon’s preference for each case in particular. We prefer to raise the infusion bottle to increase momentarily the intraocular pressure, watching pulsations of the central retinal artery. This can limit the risk of bleeding when penetrating the undiathermized retina.

If the hemorrhage is recent (<10 days) tPA can be applied in order to facilitate the clot extraction. In this case, it is ideal to use the bent 36-gauge cannula that is placed on a 1 ml syringe (tuberculin syringe) containing tPA at a concentration that can vary from 6.25 μg/0.1 ml to 25 μg/0.1 ml. per 0.1 to 0.3 ml, injecting the tPA under the neurosensory retina(23). Attention must be paid to inject directly in the interior of the clot and not contiguous to the retina or the RPE to avoid damage to cellular components. Generally the assistant injects the tPA while the surgeon pays attention so that it is injected to the interior of the clot. Occasionally it is necessary to move the cannula in order to set it in other sites in the clot. The advantage of the 33-gauge, bent, sharp, subretinal cannula is that it makes a small entrance by which

tPA does not escape from the subretinal space. Next, it is necessary to wait from 30 to 45 minutes so that tPA can lyse the clot. Scleral plugs are placed into the sclerotomy sites, and the eye is left with no movement in order to avoid tPA reflux in to the vitreous cavity. An alternative to this step is to wait only 15-20 minutes and later to irrigate and aspirate the blood, and then re-inject tPA and wait another 15-20 minutes.(44)

After sufficient time, the scleral plugs are removed and a final washing of the blood is done. There are different ways to do this. Lewis has designed a dual-barrel infusionaspirationhandpiece(38) (Infinitech,Chesterfield, MO) that makes this maneuver easier. With this instrument, the surgeon extracts the lysed blood using very low active aspiration while

the assistant slowly irrigates. It is important to pay attention that the retinal dome does not collapse to avoid the possibility of additional photoreceptor damage. Commonly there does not exist a total lysis of the clot so it is necessary to leave some remnants of the hemorrhage in the subretinal space.

In cases in which tPA is not used, retinal penetration can be made with an MVR blade tip. Next an oblique cut of approximately 120-150 degrees to the flexible silicone tip that makes easier its slipping towards the subretinal space (Figure 9) is made, limiting the mechanical damage to the RPE. The silicon tip is connected to a backflush handle in order to make alternating suction and backflush-

ing (Figure 10).(45) It is possible in this way to wash away fresh or lysed blood. In the cases in which a solid clot is still present, it is possible to increase the suction in order to grasp it and pull it into the vitreous cavity. If this mechanism fails, subretinal forceps can be used. Occasionally it is necessary to widen the retinotomy in order to facilitate the clot passage. This can be done using vertical scissors following the horizontal raphe to reduce the risk of peripheral scotomas. Unless the cut is very extensive, it is not necessary to use diathermy to cauterize the retinal vessels. We frequently use a small bubble (1-1.5 cc) of perfluorocarbon liquid(46) that can facilitate the blood expression towards vitreous cavity making subretinal maneuvers less necessary.