Ординатура / Офтальмология / Учебные материалы / Retinal Vascular Disease Joussen Springer

Table 16.1. Wide-angle viewing systems

Non- BIOM/SDI

contact Inverted image; different miniature, indirect systems viewing lenses cover a range of field of views

from 70 to 110 degrees) EIBOS

Upright image; a 90and a 60-diopter lens allow a field of view of 125 and of 100 degrees

Contact For all contact systems, miniaturization is man- systems datory to allow sufficient freedom of movement

of vitreoretinal instruments. That is why conventional diagnostic panfunduscopic lenses (as they are used, e.g., for retinal laser coagulation) are inappropriate for vitrectomy

AVI contact lens systems Inverted image Miniature contact lenses correspond to a viewing angle of 68 and 130 degrees

Volk modified the AVI System

Reinverting operating lens system (ROLS), Volk miniature indirect contact lenses with both standard lenses and the self-stabilizing lenses (58, 85, 156 diopters)

16.3 Surgical Techniques

16.3.1 Three-Port Vitrectomy

For vitreoretinal surgery in vascular disease 20gauge tools have become standard and are strongly recommended. Recently, 23-gauge instruments have been introduced to avoid sutures of sclera and conjunctiva. The use of 25-gauge instruments is controversial, since the vitrectomy part is considerably more time consuming. The authors question progress through surgical instruments smaller than 23 gauge in vitrectomy (see Chapter 20.3).

A 1.4-mm linear incision rounds out to a required 0.89-mm-diameter hole for 20-gauge instrumentation. We first place the sclerotomies for the infusion at the 3 or 9 o’clock position, using a 20-gauge beaver blade. The distance to the limbus is 3.5 mm in phakic eyes and 3 mm in aphakic and pseudophakic eyes.

Before the infusion, which is stabilized by a 7-0 suture, is opened we try to recognize the tip of the infusion canula in the vitreous cavity and free of choroid. Especially a hypotonic eye is at risk of subchoroidal or subretinal infusion. The second and third sclerotomy are placed superotemporally and superonasally.

Usually the core vitreous is removed first. As long as the posterior hyaloid is attached there is hardly any risk of peripheral iatrogenic holes. In the absence of preretinal neovascularization we attempt to induce a posterior vitreous detachment by short phases of high suction (up to 360 mm Hg) with the vitrectomy probe. Once the posterior vitreous is detached, we trim towards the base and try to avoid pulling on the peripheral retina as much as possible.

In case preretinal neovascularizations lock the hyaloid to the retina posterior vitreous, separation and trimming is attempted elsewhere. The then isolated areas of adherent vitreous cortex, possibly comple-

mented by fibrous tissue, are separately addressed II 16 using horizontally angled cutting scissors. Tight and

wide adhesions between vitreous and retina should be separated using (bimanual) delamination techniques (see Chapter 19.2.2). Panretinal photocoagulation concludes the procedure. Even though preretinal neovascularizations cannot reform in a vitrectomized eye, panretinal laser coagulation is still obligatory to address or protect from rubeosis of the iris and from rubeosis of the ciliary body.

The necessity of destroying large parts of the peripheral retina will probably not be overcome by new anti-vascular endothelial growth factor (VEGF) agents, unless we are willing to trade the permanent laser induced reduction of ischemia for endlessly repeated intravitreal injections. Whenever possible, we attempt to laser prior to vitrectomy. Laser coagulation eases vitreous separation. Possible obliteration of preretinal neovascularizations reduces the risk of bleeding during vitrectomy. The latter aspect may currently also be achieved by intravitreal injection of a VEGF antagonist. Nevertheless, the effectiveness of anti-VEGF therapy as a pre-treatment or an adjunct to surgery has to be investigated in large scale studies prior to a broad clinical application in retinal vascular disease.

Vitrectomy is concluded by filling the vitreous cavity either by BSS, gas, or silicone as needed (see below). The intraocular pressure is adjusted to normal or to a slightly elevated level. The sclerotomies are sutured tightly by 7-0 Vicryl.

So far, the authors believe that there is no advantage to 25-gauge systems as there are no medical advantages in favor of the 25or 23-gauge systems, but only patient comfort related to the smaller conjunctival lesions. The overall operating time is no shorter [20, 30].

Surgical Technique

Pars plana is today commonly performed with the help of a wide-angle viewing system, attached to an operating microscope. The sequence of surgical steps is as follows and requires modification according to the patient’s requirements:

Access to the vitreous cavity via three ports in the pars plana

Removal of the posterior vitreous, including the posterior hyaloid

Removal of tractional components by dissection techniques (e.g., delamination, en-block resection)

Treatment of avascular areas and abnormal vessels with endo-photocoagulation or intraoperative exo-cryopexy

If tamponade is required:

Fluid-air exchange with subsequent exchange of air to SF6 20 % or C3F8

16.3.2 „Chromovitrectomy“

A near complete removal of vitreous helps to prevent proliferative vitreoretinopathy (PVR). Remnants of the hyaloid serve as a scaffold for fibrovascular proliferation, e.g., in proliferative diabetic retinopathy. Due to the transparency of the vitreous, it is difficult to visualize isolated patches of vitreous on the retina. Corticosteroid crystals entangle on rough surfaces and thereby mark otherwise invisible remnants of vitreous on the retina [32, 59, 73]. No retinal toxicity has been noted in doses of 2 – 4 mg in vitrectomized and non-vitrectomized eyes [46]. In surgery for retinal vascular disease, it may help to prevent fibrin exudation because of its inherent anti-inflammatory and proliferative characteristics.

A complete removal of epiretinal fibrous membranes might help to prevent recurrence of PVR. Dyes such as trypan blue are helpful in staining epiretinal membranes. Indocyanine green selectively stains the inner limiting membrane (ILM). The epiretinal membrane is depicted in negative contrast. Remnants of ILM are easily distinguished from the unstained underlying nerve fiber layer [4].

Surgical Technique for Chromovitrectomy

After core vitrectomy one to two drops of triamcinolone acetonide in aqueous suspension (40 mg/ml) are injected via a flute needle into the vitreous cavity. Remnants of the vehicle are quickly washed out. However, to reduce the concentration of the stabilizers, the aqueous suspension can alternatively be allowed to stand for 30 min, when the crystals sediment and separate from the vehicle. The pellet of concentrated steroid is then re-suspended to the original concentration in saline

After dispersion of the crystals in the vitreous cavity, active aspiration with a vitrectomy probe or soft cannulated extrusion needle is applied

Posterior vitreous detachment, if not already present, can be created by maximal suction (200 – 300 mm Hg) just nasal to the optic disk. Once posterior vitreous separation occurs, some of the triamcinolone suspended in the midvitreous cavity settles on the dependent retinal surface

16.3.3 Heavy Liquids

Perfluorocarbon liquids (PFCLs) have become an indispensable tool to vitreoretinal surgery. The high

specific gravity of PFCLs allows the intraoperative hydrokinetic manipulation of the retina. PFCL are addressed as the “third hand” in protecting the retina from inadvertent aspiration into the cutter during “shaving” of the vitreous base. PFCLs stabilize the retina during peeling and delamination of epiretinal membranes. PFCLs displace liquefied submacular and epiretinal blood. Thereby PFCLs facilitate endolaser photocoagulation and intraoperative retinal reattachment. PFCLs can be exchanged against air or silicone oil.

Although widely used, retinal damage from PFCLs is reported after short-term use as well as from extended tamponades [7 – 9, 16, 19, 48, 64, 65]. Impurities of perfluorocarbon preparation [47, 65] may be among the limiting factors for long-term tolerance as well as dispersion of the liquids, foam cell reaction, photoreceptor toxicity and preretinal membrane formation and tractional retinal detachment. The rate of dispersion is related to factors such as turbulence, viscosity, and solubility. Miyamoto et al. described a retinal gliosis after a 1-month tamponade with perfluoroether [48]. Similarly, hypertrophy of Müller cells with bump-like protrusions into the photoreceptor interspaces was observed after only 6 days tamponade by perfluoro-octane and perfluoropolyether [16]. Whitish precipitates in the vitreous cavity and behind the lens have been reported with admixtures of vitreous and liquid perfluorocarbon bubbles or F6H8. Such precipitates represent condensed collagen without inflammatory alterations [15, 74].

In contrast to these observations, Nahib et al. observed an unchanged retinal anatomy after 6 weeks tamponade with perfluorophenanthrene [50]. Similarly, Flores described no adverse reaction in the retina after perfluoro-octylbromide tamponade of up to 6 months [19].

Although the changes described with perfluo- ro-octane, perfluorodecalin and semi-fluorinated alkanes are similar, the influence of the physical properties of these substances on retinal damage remains unknown. Perfluorodecalin differs from F6H8 with respect to its molecular weight and its specific gravity (Table 16.2). Recently, Wong and coworkers demonstrated in a model eye chamber that a complete vitreous fill of F6H8 increased the pressure on the retina by only 0.52 mm Hg [72]. Such a pressure rise is small compared to the diurnal pressure changes of the normal eye [13, 72]. Although the influence of gravity was not responsible for retinal toxicity in experimental studies (Mackiewicz, Joussen, unpublished), up until now the use of PFCLs as a long term substitute cannot be recommended. While the long term effects of PFCLs are still poorly understood, they undoubtedly are an indispensable intraoperative tool.

Tips and tricks for the use of liquid perfluorocarbons during surgery:

Liquid perfluorocarbon and blood: Liquid submacular blood or epiretinal blood can be displaced to the periphery by liquid perfluorocarbon. Inject PFCL slowly, to avoid a stronger jet of PFCL. Such a jet stream can create retinal holes and PFCL ends up subretinally. Filling the eye with PFCL facilitates endophotocoagulation in two ways: firstly by displacement of blood, and secondly by appositioning the retina against the pigment epithelium, where the heat evolves

Direct exchange of silicone oil against liquid perfluorocarbon: Filling the eye with PFCL until the level of the infusion is indicated by bubble formation. Bubbles of PFCL may end up subretinally, either through peripheral retinal holes or via retinotomies/retinectomies. Subretinal “pearls” of PFCL tend to slide towards the macula during PFCL-sili- cone oil exchange. Subretinal PFCL is often perceived only postoperatively. Submacular PFCL must be removed. It causes slowly progressive visual loss. Bubbles of PFCL may be become entangled in the vitreous base and retained in the eye. Therefore, one should avoid a complete or near complete PFCL coat of the retina. Therefore, allow some time for the PFCL to flow to the posterior pole

PFCL can be exchanged against air or silicone oil. For the latter, the silicone oil should be layered over the PFCL. The adhesion of PFCL to silicone oil evacuates most of the remaining water through the sclerotomies. The less water that remains in the eye, the more complete the silicone oil fill will be

Liquid perfluorocarbon is helpful in the removal of “sticky silicone oil“: Seldomly removal of heavy silicone oil is complicated by a rather tight adhesion to the retina (see below). Adhesion of heavy silicone to PFCL is even greater than adhesion of heavy silicone to the retina. Therefore PFCL can be used to collect heavy silicone oil from the surface of the retina like a “sticky tape.” Finally, the conglomerate of PFCL and heavy silicone can be removed from the eye via the flute needle

16.3.4 Vitreous Tamponades

16.3.4.1 Gas Tamponades

The use of intraocular gases was first reported for the treatment of retinal detachment in 1911 by Ohm, who treated two patients by injecting air into the vitreous cavity after drainage of subretinal fluid [55]. Gases gained popularity in the treatment of retinal detachment due to their unsurpassed interfacial ten-

sion against water. The greater the interfacial tension the larger the retinal hole to be blocked can be. Norton [54], Machemer [42], and Lincoff [40, 41] developed the application to the eye and today a family of straight chain perfluorocarbon gases is available with varying ability of expansion and longevity.

For advanced cases of neovascular retinal disease a long-term tamponade is usually required. Nevertheless, there are patients in whom silicone oil for a variety of reasons is avoided and in whom a gas tamponade, usually with sulfur hexafluoride (SF6), is beneficial.

Sulfur hexafluoride (SF6) is a colorless non-toxic gas, approximately 5 times heavier than air [45]. SF6 is chemically inert and hydrolysis requires extremely high temperatures.

Intraoperatively, gases facilitate the view to the retinal periphery. Gases do not mix with blood and do not convey (tumor) cells. Thus, endolaser coagulation of the peripheral retina or endoresection of choroidal melanomas is best performed under gas. On the other hand, localization of retinal holes is hampered by a gas fill.

Tips and tricks for surgery with gas tamponades:

Reproducible gas filling

Before the infusion line is removed from the air filled eye, the vitreous cavity is flushed by 50 cc of 20 % SF6. The airSF6 admixture is injected via a 30-gauge needle through a separate pars plana puncture. Surplus gas is pushed back into the air infusion line and air pump

Avoid drying of retina

Welch et al. have shown that the air jet of the infusion line causes large temporal field defects, from dried retina typically nasal to the disk [67]. It is advisable to use humidified air or plug the sclerotomies when instruments are removed from the eye for extended periods

Improving vision to the retina

During fluid gas exchange, fogging of an artificial intraocular lens (IOL) is often encountered on the posterior surface within the area of a capsulotomy. Healon, applied to the back of the IOL, eliminates the fogging and reestablishes full visibility

16.3.4.2Extended Vitreous Tamponade with Silicone Oil

Silicone oil was introduced to vitreoretinal surgery in 1962 by Cibis [11]. With the advent of vitrectomy

[43] and through Ando’s 6 o’clock iridectomy [5], silicone oil has widened our indications to, e.g., severely injured eyes so far beyond remedy.

Silicone oils are linear synthetic organic polymers 16 II with a common macromolecular backbone made of siloxane (-Si-O) repeating units. The major differences among silicone fluids reside in the chemical structures of radical side groups, in radical termination of the chains, and in the size distribution of chains. In ophthalmology, the term silicone oil has been used to designate any of the viscous hydrophobic

polymeric compounds based on siloxane chemistry.

Physical Properties and Clinical Consequences

of Silicone Oils

In the eye, the dynamics of the silicone oil tamponade involves buoyancy, interfacial surface tension, and viscosity.

In a liquid, the cohesive forces generated by the molecular attraction between closely packed molecules generate friction, a resistance to fluid flow. The amplitude of this resistance is represented by the fluid coefficient of kinematic viscosity [17, 18], usually expressed in centistokes (cSt). Increasing a silicone oil’s molecular weight results in an increased polymer chain length and, consequently, an increase in viscosity.

Clinically used silicone oils are highly purified polydimethylsiloxanes with a viscosity of 1,000 – 5,000 cSt. Low-viscosity silicone oils are preferred by some surgeons because of their quicker filling into the vitreous cavity and removal from the vitreous cavity. While initially silicone oils of 1,000 cSt were used, there is currently a trend to use oils of higher viscosity.

One of the main problems in the clinical use of silicone oil is emulsification. Fine silicone oil droplets can cause a secondary glaucoma by blocking aqueous outflow. Heidenkummer and coworkers investigated the effect of viscosity of highly purified polydimethylsiloxanes in the presence of biological detergents (albumin, acidic alpha-1-glycoprotein, fibrin, fibrinogen, gamma-globulins, and very-low-density lipoprotein). Silicone oil at 5,000 cSt was in all cases distinctly more stable than the silicone oils with a viscosity up to 4,000 cSt independent of the detergent [23].

Interestingly, viscosity did not affect functional and anatomical outcome after retinal detachment. There was no significant difference in the rate of retinal re-detachment at each of the follow-up intervals [60].

Patients with proliferative retinal disease and likewise patients with PVR are more prone to emulsification due to their high amount of biological detergents from blood-retina barrier breakdown. Thus

silicone oil of 5,000 cSt seems to be superior to 1,000 cSt silicone oil from the authors’ point of view. There are, however, at this point no randomized clinical trials available to support this hypothesis.

Heavier than Water Silicone Oils

Perfluoroalcanes are heavier-than-water transparent liquids which are tolerated by the retina [74]. Perfluorhexyloctane (F6H8) has recently gained attention as a long term vitreous substitute [33]. However, surgeons are concerned about inflammation in the eye [35, 62, 66]. Although F6H8 is chemically and biologically inert [74], its low viscosity promotes emulsification. Minute bubbles subsequently trigger chemotaxis of inflammatory cells and phagocytosis [36].

Heavy silicone oil theoretically offers the chance to reduce the rate of tractional late retinal re-detach- ments [56] through displacement of the PVR stimulating modulators from the inferior retina. Preliminary consecutive observations of 40 patients treated by a heavy silicone oil tamponade [69] and further series [63, 74] do not disprove this hypothesis.

The heavy silicone oil Densiron 68 (HSO 68-1500) is a transparent homogeneous liquid which is slightly heavier (1.06 g/cm3) than water. Densiron 68 is a mixture of 5,000 mPas silicone oil (specific gravity of 0.97 g/cm3) and of 3.5 mPas F6H8 (specific gravity 1.33 g/cm3). Densiron 68 has a low viscosity (1,480 mPas).

While the use of silicone oil in vitreoretinal surgery for vascular disease is common, heavy silicone oils are currently gaining importance and not only in the treatment of inferior PVR. The stickiness of the heavy silicone oil is sometimes reported as a problem during removal. On the other hand, the stickiness adds to the effect of gravity, namely by blocking access of inflammatory mediators within the vitreous from the retina. The stickiness brings about a “sealing” effect, preventing spread of hemorrhage from retinal or chorioretinal wounds in the inferior retinal periphery, e.g., after chorioretinal biopsy or translocation. Finally, heavy silicone oil exempts the patient from positioning (macular hole surgery). It even achieves closure of macular holes refractive to conventional gas tamponade (Rizzo, unpublished).

Silicone Oil as a Drug Carrier

Current treatment approaches in retinal vascular disease focus on prevention in earlier stages of the disease (see, e.g., Chapter 19). Surgery will probably be reserved for late stage disease and rare entities with otherwise untreatable vascular abnormalities.

With inert tamponades such as silicone oil, there are two possible ways of delivering the drugs: either

the agents concentrate in the remaining watery phase, or they dissolve within the silicone oil. In the best case scenario, the silicone oil can act as a slow release system.

Nevertheless these slow release systems using silicone oil as a drug carrier are currently at an experimental level and are not clinically applicable. When used for retinal tamponade in experimental proliferative vitreoretinopathy, silicone oil was investigated as a vehicle for delivery of a lipophilic antiproliferative agent [3]. However, histopathologic examination of the eyes injected with this antiproliferative agent and silicone oil indicated some retinal disorganization even at the lower therapeutic levels. Similarly, retinoic acid was evaluated in silicone and siliconefluorosilicone copolymer oils in a rabbit model of proliferative vitreoretinopathy. Retinoic acid, in this model, was found to be useful in PVR treated with silicone oil or for eyes treated intraoperatively with heavier-than-water silicone oil when it is used as a short-term retinal tamponade [51]. To improve release profiles, biodegradable microspheres of poly (DL-lactide-co-glycolide) (PLGA) for intraocular sustained release of ganciclovir were prepared using a dispersion of ganciclovir in fluorosilicone oil (FSiO) that was further dispersed in an acetone solution of PLGA (50/50 and inherent viscosity 0.41 dl/g), and emulsified in silicone oil with a surfactant [27]. So far, there is no broad clinical application.

For retinal vascular disease the admixture of triamcinolone is of great interest, given the effect on vascular permeability, e.g., in macular edema (see Chapters 19.3.1 – 19.3.3).

The clinical outcome and complications associated with intravitreal injection of unaltered triamcinolone acetonide in conjunction with pars plana vitrectomy and silicone oil injection for the treatment of complicated proliferative diabetic retinopathy with tractional retinal detachment and severe proliferative vitreoretinopathy were recently presented in retrospective evaluations. Up to 4 mg of triamcinolone acetonide can be safely injected in silicone-filled, vitrectomized eyes without any significant retinal toxicity [34, 49]. It should, however, be expected that the triamcinolone crystals cumulate in the watery phase and form a sticky tablet-like deposit that can remain for several months.

When to Remove a Silicone Oil Tamponade?

Although a long-term tamponade is possible with silicone oil, secondary glaucoma due to emulsification is a considerable threat.

Chronic intraocular pressure elevation occurs in a minority (11 %) of patients who are treated with silicone oil. Most of these eyes are effectively treated

patients with severe proliferative diabetic retinopathy (48 eyes) and 39 eyes with complex proliferative vitreoretinopathy or giant retinal tears after trauma. In 75 % of proliferative diabetic retinopathy patients the retina remained attached; this is in contrast to patients with proliferative vitreoretinopathy, of whom only 48.5 % remained stable [31]. Interestingly, the success was independent of the duration of intraocular silicone oil tamponade in proliferative diabetic retinopathy.

There is no general rule as to the required duration of silicone oil tamponade. It is assumed that the silicone oil exerts some decompartmentalization effect and thus contributes to the settlement of active proliferation by evacuating the growth factor reservoir of the vitreous. Usually active proliferative disease after vitrectomy, endolaser coagulation and silicone oil tamponade will require a minimum of 8 – 10 weeks to settle. The authors favor silicone oil removal at the earliest possible time point (mostly after about 3 months) to avoid secondary cataract formation, optic atrophy, or glaucoma.

Silicone oil in the anterior chamber is associated with a specific complication profile and results in secondary glaucoma, decreased visual acuity by corneal decompensation and band keratopathy.

To avoid silicone oil passage into the anterior chamber in phakic and pseudophakic eyes, intraoperative overfill should be avoided. Prompt surgical removal of the silicone oil from the anterior chamber is usually the preferred method. We favor a technique with two paracenteses. A superior paracentesis in the 12 o’clock position allows outflow of the oil. With pressure of a spatula on the posterior lip, this paracentesis can be opened. The eye is rotated inferiorly. If all the silicone oil can be removed with this technique, no further intervention is required. In some cases, complete removal of the silicone oil requires viscoelastics (e.g., hyaluronic acid) to be injected via a second paracentesis at 6 o’clock and express the silicone oil via the superior paracentesis. Usually the viscoelastic is subsequently rinsed out; however, if left behind in the anterior chamber a close monitoring of the intraocular pressure is required in the postoperative phase. The superior paracentesis is finally closed with a 10-0 nylon suture.

In aphakia, an inferior peripheral iridectomy (Ando iridectomy) prevents postoperative migration of silicone oil into the anterior chamber [5]. The

Tips and tricks for surgery with silicone oil tamponades:

“Sub-silicone oil” proliferation is probably not a chemical effect of the oil but the consequence of compartmentalization, that is concentration of wound healing factors (blood ocular barrier breakdown) under the oil bubble

Direct exchange of heavy liquids (perfluoroctane, perfluorodecaline) with silicone is possible just the same as via an intermediate step of air

Silicone oil removal should be aimed at and is usually possible after about 3 months

Heavy silicone deserves further investigation as the physical means to inhibit PVR of the inferior retina via displacement of growth factors, such as hemostypicum, and as tamponade medium for persistent macular holes allowing supine positioning

16.3.5 Endolaser Coagulation

The endolaser has significantly altered the indication profile of vitreous surgery for retinal vascular disease. When initially introduced to vitreoretinal surgery, endo-photocoagulation was used to treat retinal tears, stop bleeding, apply scatter photocoagulation, coagulate ciliary processes and enlarge the pupil in eyes with miotic pupils and iris neovascularization [10, 57]. These indications are so far still valid and in use.

Today endolaser probes are in use for argon and diode lasers. The intensity of the laser burn depends on the duration and power settings of the laser and the working distance of the endolaser tip from the retinal surface and the angle thereof. Furthermore, the degree of underlying pigmentation is important and blood on the retinal surface should be avoided (see heavy liquids) in order to prevent excessive retinal scarring.

In panretinal endolaser photocoagulation the laser pattern is similar to that obtained using the slit lamp or indirect laser delivery systems. Scleral depression in conjunction with an illuminated probe eases the application to the retinal periphery without lens touch.

In the gas or air filled eye the view to the peripheral retina is facilitated. However, retinal holes are more difficult to discern under air. It may be useful to coagulate and mark the central rim of retinal breaks under liquid perfluorocarbon, and complete retinopexy of the peripheral rim after the fluid-air exchange.

Laser coagulation of abnormal retinal vessels aims at the destruction of these vessels. Long expo-

sure times are important and repetitive treatment may be required. Nevertheless, caution is necessary, e.g., in coagulation of aneurysms, in applying endolaser to areas of vascularized retina in order to prevent inadvertent vascular occlusions.

Complications of endolaser photocoagulation include retinal necrosis, choroidal neovascularization and retinal tears that occur after very intensive spots. “Popping” effects should be avoided. These can be avoided by careful adaptation of the laser energy and distance of the endoprobe.

16.3.6Lens Management and Compartmentalization

In eyes with dense cataracts not only the patient’s visual acuity, but also the fundus view is obscured and the necessary panretinal photocoagulation is not possible to an adequate extent. In some cases the use of a krypton laser with a wavelength in the range of 600 nm is advantageous in transcending a nuclear cataract.

In cases of proliferative retinopathy, panretinal photocoagulation prior to cataract surgery is advised. Otherwise, small incision surgery allows for photocoagulation within a short time after cataract extraction.

Phaco-emulsification with implantation of a posterior chamber lens is today generally accepted in eyes with proliferative retinopathy. Previous reports on the stimulation of rubeosis following IOL implantation showed no or insufficient laser treatment. In order to facilitate later panretinal photocoagulation or vitrectomy, a large capsulorrhexis is required as well as an IOL with a large optic. The combination of cataract removal, vitrectomy and endophotocoagulation was only in small case series reported to be associated with a higher risk for neovascularization of the iris [6, 37]. Acryl is the recommended lens material, as these IOLs can be folded and implanted in small incision surgery. Silicone oil tends to stick like glue to silicone lenses.

Cataract surgery without IOL implantation is best performed by endophaco-emulsification. Complete removal of the capsule prevents secondary fibrosis and closure of an eventual (Ando) iridectomy.

Tips and tricks for lens management during vitreous surgery for proliferative retinal diseases:

It is worthwhile discussing keeping the iris-lens diaphragm in order to avoid growth-factor diffusion to the anterior segment via the vitreous cavity

Silicone IOLs should be avoided in all patients with vascular disease as they might require silicone oil tamponade at some point, which then may stick to the lens material

Large capsulorrhexis and large optics facilitate future inspection of the peripheral retina

Removal of IOLs in association with vitreous surgery can easily be performed via pars plana

If no lens implantation is planned, a pars plana lentectomy can easily be performed in conjunction with vitrectomy

16.4Indications for Vitreoretinal Surgery in Retinal Vascular Disease

With the current techniques, the three major indications for vitreoretinal surgery in retinal vascular disease are:

Destruction of ischemic retina and pathological vessels

Removal of dense vitreous opacities

Release of traction and retinal detachment repair

16.4.1Destruction of Ischemic Retina and Pathological Vessels

It has been shown previously that anti-VEGF therapies are able to reduce rubeosis and limit macular edema by enhancing vascular stability. Recent data has identified the molecular mechanisms which are involved in the ischemic reaction (see Chapter 7). Nevertheless, anti-VEGF therapy alone will not amend large avascular areas and in the retina, but photocoagulation will remain the treatment of choice to reduce the stimulus for neovascularization sustainably. Panretinal photocoagulation reduces the release of VEGF, causes the RPE to release inhibitory substances (TGF-) and increases choroidal oxygen transport to the retina [1, 58]. Argon, krypton, or preferably diode-pumped, frequency-dou- bled YAG (532 nm) lasers can be used. A detailed rationale of photocoagulation is given in Chapter 13 and in Sect. 16.3.5 of this chapter. In rare instances neovascularization does not regress despite supposedly complete panretinal coagulation: If there is any doubt about a sufficient photocoagulation, it is advisable to further intensify the treatment and increase the number of laser spots per area. If it is certain that panretinal photocoagulation is complete, then vitrectomy plus silicone oil tamponade aims at regression/prevention of rubeosis and ciliary body neovascularization, and at remedy of preretinal neovascularization. Preretinal neovascularization requires the presence of hyaloid [70].

Vitreoretinal surgery and vitrectomy itself cannot reduce ischemia as well, but posterior vitreous detachment may help to remove the scaffold for cellular vitreoretinal traction. Removal of the vitreous

16.4.2Removal of Dense Vitreous Hemorrhages

One of the most frequent reasons for vitrectomy is persistent vitreous and preretinal hemorrhage. Vitreous hemorrhage is most likely a consequence of ruptured neovascularization at the vitreoretinal interface secondary to a (usually partial) posterior vitreous detachment. Vitreous hemorrhage can occur in any proliferative disease.

„Early vitrectomy” should be considered in eyes with vitreous hemorrhage, precluding laser application, not resolving within 4 – 8 weeks. The general aim of the treatment is an early adequate panretinal photocoagulation (including the outer retinal periphery). As described above, it is advantageous to perform the panretinal photocoagulation intraoperatively using an illuminated laser probe and scleral indentation to complete the treatment to the peripheral retina.

Timing of the vitrectomy depends on the underlying disease, the age of the patient, and visual acuity of the contralateral eye. In cases of dense hemorrhage, a preoperative ultrasound examination (B- scan) is advisable to assess the macula. If retinal detachment is close to extending into the macula, or if the macula has detached only recently, then vitrectomy should be performed in due course. Early vitrectomy is further advisable in eyes lacking previous panretinal photocoagulation. In diabetics, a severe progressive proliferation of the fellow eye is another reason to perform vitrectomy instantly [12, 61]. In these conditions surgical treatment of vitreous hemorrhage in fellow eyes may help to prevent progression to a tractional retinal detachment. In any case of associated anterior segment neovascularization (either rubeosis iridis or manifest neovascular glaucoma) vitreous hemorrhage is an indication for early surgical intervention. Only instant vitrectomy and complete panretinal photocoagulation is able to inhibit progression of the neovascular process and to prevent occlusion of the chamber angle [29].

16.4.3 Release of Traction

In proliferative vitreoretinal diseases (diabetes, PVR), vitrectomy may not only remove growth factors from the vitreous cavity but also the scaffold to which contractile cells adhere and by which tractional forces are transmitted to the retina. Removal of the vitreous or spontaneous posterior vitreous separa-

In severe ocular trauma, vitrectomy eliminates a considerable part of the risk of vitreoretinal traction. However, contractile cells attach not only to vitreous collagen but also to retinal surfaces. Trauma derived strands are able to detach the retina without vitreous interposition. Thus, in severe ocular trauma in addition to vitrectomy additional regimens are recommended (pharmacological adjuncts: 5-FU, daunomycin).

In PVR as a complication of rhegmatogenous retinal detachment, contractile cells adhere to vitreous collagen and to the retinal surface. Since floating cells settle down, star folds develop typically on the inferior retina. Usually the posterior hyaloid is already detached at the time of retinal detachment. Thus vitreoretinal traction (anterior-posterior, circumferential) is most likely to be found at the peripheral retina, in the area of the inferior vitreous base (Figs. 16.1, 16.2).

PVR is considered an undesired wound healing response. It requires both contractile cells and inflammatory mediators deriving from blood ocular barrier breakdown. If one of the two “partners” is

missing, PVR is unlikely to occur. PVR is not a typi- II 16 cal complication of uveitis, where there is prominent

blood ocular barrier breakdown but no contractile cells to respond to. PVR is not a typical complication of retinal holes when the retina is attached. There are potentially contractile cells (RPE cells), but inflammatory modulators are absent. Rhegmatogenous retinal detachment, however, features both blood ocular barrier breakdown plus contractile cells. The RPE is exposed to the vitreous milieu via the retinal hole. In untreated or longstanding rhegmatogenous retinal detachments PVR is a common manifestation (Fig. 16.3).

Physical separation of cells and growth factors is thought to reduce recurrence of PVR. Since PVR is

270 II General Concepts in the Diagnosis and Treatment of Retinal Vascular Disease

Inflammation + Cells

16 II

PVR

Fig. 16.3. Uveitis (left) shows blood ocular barrier breakdown, and no retinal holes. Atrophic holes in attached retina (right) are usually not seen along with blood ocular barrier damage. Rhegmatogenous retinal detachment (middle) has an overlap of both responsive fibroblastic cells and inflammatory environment. The retina is detached and wrinkled indicating indirectly epiretinal membrane formation

predominantly observed at the lower retina, a heavier than water tamponade, either semifluorinated fluorocarbon, or heavier than water silicone oil, is presently being tested in a prospective randomized study (HSO, Cologne, Germany) (Fig. 16.4).

A relatively new indication for vitrectomy is persistent macular edema. Diabetic macular edema is a consequence of a blood-retinal barrier breakdown, but also tractional forces in the macular area are involved in its pathogenesis.

Since 1996, surgical intervention for macular edema has been more frequently reported. The observation that a posterior vitreous detachment is less frequently found in patients with diffuse diabetic macular edema, led to the assumption that a posterior vitreous detachment could be therapeutically efficient [52, 53]. Hikichi and coworkers reported a resorption of macular edema in 55 % of patients after posterior vitreous detachment compared to 25 % with attached posterior vitreous [28].

Since then, multiple authors have demonstrated that vitrectomy including removal of the posterior vitreous results in a reduction of macular edema and potential improvement of visual acuity [21, 22, 39]. So far, there is no randomized clinical controlled trial available proving the advantage of ILM peeling in macular edema (see Chapters 19.3.1 – 19.3.3).

References

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