Ординатура / Офтальмология / Английские материалы / Retinal Vascular Disease_Joussen, Gardner, Kirchhof_2007

part useful for RCA with significant exudation, particularly for RCA with a size which may not be evaluable for laser treatment. However, the observations of the literature are based on case reports and small case series.

Juxtapapillary RCA

A prospective case series of five patients [64] with symptomatic juxtapapillary RCA was treated with PDT using 6 mg/kg (body surface area) verteporfin and a light dose of 100 J/cm2. Twelve months after beginning the PDT treatment sessions subretinal exudation with involvement of the macula was resolved, and the size of the RCA was regressed in all out of five patients. The final mean visual acuity decreased from 0.22 (range 0.5 – 0.025) to 0.1 (range 0.32 – 0.01). A decrease of 1, 3 and 10 lines was observed in three patients. The visual acuity of the remaining two patients was stable (0.05) and increased slightly (from 0.063 to 0.1). However, occlusion of retinal vessels and ischemia of the optic nerve occurred in three out of five patients. Therefore the positive effects of PDT on the subretinal exudation and the size of RCA were limited by the adverse effects on visual function of patients with juxtapapillary RCA.

14.5.2 Vasoproliferative Tumor

14.5.2.1 Characteristics

This vascularized retinal tumor lesion is located particularly inferotemporally and anterior to the equator of the fundus periphery. Usually the artery feeder vessel and the draining vein are dilated to a lesser extent compared to those of the RCA. Fluorescein angiography reveals features similar to those of the RCA. However, in addition to subretinal exudation, hemorrhages, preretinal fibrosis and gliosis of the macula with a decrease in visual function may be possible findings. They may be observed idiopathi-

cally and in combination with retinitis pigmentosa, intermediate uveitis, inflammatory diseases, ocular toxocariasis, sickle cell retinopathy, Coats’ disease, and chronic retinal detachment, respectively [23, 67]. Therapeutic interventions may be necessary for vasoproliferative tumor (VTR) with progressive exudation, symptoms and decrease in visual function.

14.5.2.2 Treatment Recommendations

While laser photocoagulation, cryocoagulation and brachytherapy with ruthenium plaques are usually the treatment forms of VTR [3, 23, 67], PDT has been shown to be an effective alternative as reported in case reports and small series of prospective case series [7, 9, 51]. Effective treatment sessions have been performed with a light dose of 100 J/cm2 and 5 min after infusion of verteporfin (6 mg/kg body surface area).

14.5.2.3 Effects of PDT

Similar to the observations found with RCA after PDT occlusion of the VTR, vessels can be detected after PDT. Resolution of the subretinal exudation, a decrease in tumor size and an increase in visual function have been reported after up to two treatment sessions, while recurrences were not detected after a follow-up time of 7 – 12 months [7, 9, 51].

14.5.3 Parafoveal Teleangiectasis

14.5.3.1 Characteristics

Parafoveal retinal teleangiectasis is characterized by dilated parafoveal capillaries, which may lead to exudation and macular edema. Other findings may be right angle venules, capillary occlusion, atrophy and hyperplasia of the RPE, retinal crystals and lipids, and CNV due to parafoveal teleangiectasis [18]. The findings, which may be unilateral, bilateral, focal, diffuse around the parafoveal region, depend on the

subtype of parafoveal teleangiectasis. Fluorescein angiography reveals irregular parafoveal capillaris, which may be combined with leakage into the retina

14 II and macula, defects of the RPE [18].

14.5.3.2 Treatment Recommendations

Laser photocoagulation should be considered in the presence of visual loss due to macular edema and exudation, particularly for Type I teleangiectasis [18]. However, other treatment modalities are currently under investigation.

14.5.3.3Effects of PDT on Parafoveal Teleangiectasis

A few case reports investigated the treatment of juxtafoveal telangiectasis with PDT. No beneficial effects on the visual acuity and on the macular edema were observed after final PDT [11]. In contrast, case reports and case series [27, 46, 70] reported at least in part positive effects of PDT on CNV due to idiopathic juxtafoveal retinal teleangiectasis: Compared to the baseline examinations prior to PDT and after a mean follow-up of 21 months, visual acuity was stabilized in two eyes (decrease and increase of less than 1 line), improved in three eyes (1 lines) and decreased in two eyes (decrease of 1 line), while no leakages were detected after the final examination of the seven study eyes [46]. However, an atrophy of the RPE corresponding with the size of the laser spot followingPDT has been documented in patients with CNV due to parafoveal teleangiectasis [65]. Therefore, prospective studies are required to confirm the beneficial effects of PDT on patients with CNV due to parafoveal teleangiectasis.

14.6 Conclusions

Photodynamic therapy with verteporfin has significantly improved the prognosis of several diseases of the macula involving the choroidea, choriocapillaris and retina. There is at least in part a selectivity of the PDT treatment which may contribute to stabilization of the visual function. PDT has been established for the treatment of CNV (depending on the combination of the lesion type) and choroidal hemangiomas, respectively. However, experience of PDT treatment of retinal diseases is limited. This may at least in part be caused by the low incidence of specific retinal diseases suitable for the treatment option of PDT. However, the results of several case series suggest that PDT represents an effective treatment option for retinal capillary hemangiomas and vasoproliferative tumors. This may depend on the clinical findings and the localization of the lesion. Further investiga-

tions will define the role of PDT in the treatment of retinal diseases as single therapy and as a combination with pharmacologic and anti-angiogenic agents, respectively.

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40.Moan J, Christensen T (1981) Cellular uptake and photodynamic effects of hematoporphyrin. Photochem Photobiol 2:291 – 299

41.Moan J, McGhie J, Jacobsen PB (1983) Photodynamic effects of cells in vitro exposed to hematoporphyrin derivative in light. Photochem Photobiol 37:599 – 604

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B. Kirchhof, A.M. Joussen

15 II

Core Messages

Cryotherapy is applied to generate chorioretinal scars, to reduce retinal ischemia or to occlude abnormal retinal vessels

Repetitive treatments are necessary to achieve permanent obliteration of vascular abnormalities

Cryotherapy is superior to laser coagulation in the case of media opacity and in shallow (exudative or tractional) retinal detachments

The freeze zone of cryoburns has a better depth than the zone of destruction after laser

Cryotherapy has a long history in the treatment of retinal vascular disease. Freezing the retina to create inflammation in the area of application began as early as 1918, when Schöler applied solid carbon dioxide to the sclera and described choroidal inflammation [9]. In the treatment of proliferative retinopathy, cryotherapy today has largely been replaced by laser photocoagulation. However, the transscleral mode of application renders cryotherapy particularly useful in the case of hazy media or cataracts. It is also useful in treating more peripheral lesions that cannot be easily visualized at a slit lamp.

Cryotherapy induces a greater breakdown of the blood-ocular barrier, which has been implicated in the risk of cystoid macular edema, choroidal detachment and exudative retinal detachment. Laser flare photometry showed a greater increase in aqueous flare and a slower recovery of visual acuity after limited external retinal cryotherapy compared to laser coagulation. However, this difference did not affect visual acuity 10 weeks after treatment [13].

Cryotherapy in retinal detachment surgery has long been associated with a number of postoperative events, including macular pucker and proliferative vitreoretinopathy (PVR) due to dispersion of viable pigment epithelial cells and breakdown of the bloodocular barrier. However, blood-ocular barrier breakdown is clinically irrelevant if excessive cryoapplication is avoided, and if applied to eyes with uncompli-

treatment. Therefore cryotherapy is especially useful for smaller tumors

The freeze zone of cryoburns is wider, about 3 – 8 mm, than laser burns. Transition and

demarcation of the intact retina are less abrupt. Therefore cryotherapy is especially useful when a strong vitreoretinal adhesion is attempted.

The shallow transition to the intact retina weakens the retina less than laser burns and thereby largely avoids tears at the edge of the chorioretinal adhesions

cated retinal detachment, and without significant preoperative PVR. In comparison, transscleral diode laser did not show better results in retinal detachment surgery [12].

In the treatment of ischemic retinal diseases, mobilization of retinal pigment epithelium (RPE) cells and risk of PVR does not apply as for the lack of retinal holes. Blood-retinal barrier breakdown, however, will be temporarily aggravated.

The pathology of cryotherapy lesions has been well investigated. The formation of retinal scars includes desmosomal connection between the Müller cells and the basement membrane of RPE. Processes of Müller cells infiltrate the collagen lamellae of Bruch’s membrane [3 – 5]. Laboratory studies have shown that there is little difference in the strength of the chorioretinal scar created by laser photocoagulation and by cryotherapy [1, 15].

It usually takes about 5 – 7 days for a chorioretinal scar to complete. The repair and remodeling after cryotherapy vary depending on the intensity of the application. For treatment of vascular abnormalities repetitive freezing of the choroid and the outer retinal layers (3 times) is mandatory.

Although laser photocoagulation in many indications has replaced cryocoagulation, cryotherapy is still used as adjunctive treatment in the therapy of vascular disease.

Essentials

Equipment needed: Cryoprobe

Indirect ophthalmoscope

Condensing 20and 28-dpt lenses for indirect ophthalmoscopy

Lid speculum

Topical anesthetic

Local anesthetic for injection (e.g., 4 % Xylocaine without epinephrine)

Mydriatic eye drops

A variety of probe tips and cryotherapy machines are available; most are gas operated. Most cryosurgical units use either carbon dioxide or nitrous oxide gas and are based on the Joule-Thompson principle that a sudden drop in temperature occurs when pressurized gas is allowed to expand through a narrow aperture. The tube is defrosted by a passage of another warm gas, or the same gas under low pressure. A silicone sleeve limits the cooling effect to the tip of the probe. When nitrous oxide gas is used, a pressure of 600 psi is sufficient to produce cooling up to –89 °C.

The surgeon should be certain that the shaft of the probe is insulated, and test the freezing before usage. Treatment should be controlled via indirect ophthalmoscopy. The freezing should be terminated soon after a distinct whitening of the neurosensory retina is observed.

In general subconjunctival anesthesia is sufficient for cryotherapy.

A quantity of 0.2 – 0.3 ml of 4 % Xylocaine is injected subconjunctivally in the quadrant requiring therapy. After 10 – 15 min, sufficient anesthesia is achieved and treatment may be started. For treatment of children general anesthesia should be given priority.

For applications close to the posterior pole it is necessary to open the conjunctiva.

Usually a few seconds are sufficient to achieve a sustained freezing until the retina first turns white. After thawing, a faint gray area representing intraretinal edema is all that remains of the cryoapplication. Prolonged freezing is necessary when subretinal exudation increases the distance between the retina and cryoprobe. The probe should not be removed until thawing is completed to avoid retinal breaks.

Postoperative medications are rarely necessary, but antibiotic ointment can be applied.

II 15

Fig. 15.1. A section of normal retina demonstrating penetration of cryogenic necrosis (represented by columns) to the outer limiting membrane after a light application (L); to the nerve fiber layer after a medium application (M); and to the internal limiting membrane after heavy application (H). (With permission from Ingrid Kreissig (ed): Minimal surgery for retinal detachment. Thieme, Stuttgart, 2000, p. 104)

Complications of treatment itself, such as corneal abrasion, subconjunctival hemorrhage and intraocular hemorrhage, are rare. If an intraocular hemorrhage under treatment should occur, pressure on the eye helps to stop the bleeding. It is possible to perforate the sclera (thin sclera in myopia or reoperation) with the cryoprobe when using as a scleral depressor. In that case the wound needs to be treated like a rupture or penetration of other origin.

Depending on the duration of freezing, chorioretinal scars develop that vary in scleral penetration. Cryogenic necrosis reaches the outer limiting membrane after light application, but can also include the full retinal thickness including the superficial retinal vasculature after heavy application (Fig. 15.1).

Endocryocoagulation is indicated during vitrectomy when endophotocoagulation is insufficient to completely obliterate pathologic retinal vessels, e.g., in Coats’ disease or familial exudative vitreoretinopathy (FEVR). The endocryoprobe is inserted through the sclerotomy and the tip held without pressure in close apposition to the retina. While freezing, the tip is tightly connected to the retinal tissue. While the frozen part of the retina is rigid, the surrounding tissue can easily tear. Thus the tip of the endoprobe must not be moved while freezing. Complete thawing should be awaited before removing the probe from the retina. Unlike laser burns, cryotherapy does not show an immediate treatment effect on the retina.

Jandeck et al. discuss in detail elsewhere in this book the value of cryotherapy in retinopathy of prematurity (ROP) (Chapter 20.2). The benefit of cryotherapy for treatment of threshold ROP for both structure and visual function that was demonstrated in the CRYO-ROP study was recently shown to persist over 15 years of follow-up [8]. However, new retinal detachments may occur as late as 10 years after treatment and suggest value in long-term, regular followup of eyes that experience threshold ROP.

Comparing laser photocoagulation with cryotherapy in patients with threshold ROP, laser-treated eyes had better structural and functional outcome [7]. Similarly, in a report by Jandeck [2], the results of laser therapy were superior to those of cryotherapy, indicating that laser treatment is the therapy of choice: an “unfavorable outcome,” as described in the CRYO-ROP study, occurred in 1 of 91 (1 %) eyes with laser treatment and in 3 of 46 (6.5 %) eyes with cryotherapy. Temporal dragging of vessels was noticed in 6 of 91 eyes (6.6 %) with laser treatment vs 7 of 46 eyes (15.2 %) with cryotherapy, respectively. Visual acuity 20/25 was achieved in 39.2 % of eyes with laser therapy and in 17.6 % with cryotherapy (p < 0.05).

Nevertheless, while the primary choice for treatment of the peripheral avascular zone on ROP is laser photocoagulation, additional cryotherapy can be valuable in cases with media opacities such as cataracts or a tunica vasculosa lentis that absorb the laser light and prevent sufficient treatment. Cryotherapy is also to be considered in addition to laser therapy in patients with very central disease when the larger spots of the cryoprobe are advantageous to filling the avascular area. However, cryotherapy should only be used to fill the gaps when treatment with photocoagulation is incomplete.

15.2.2Cryotherapy for Diabetic Retinopathy and Retinal Ischemic Disease

The gold standard for the treatment of neovascularization associated with diabetic retinopathy or central vein occlusion is laser photocoagulation.

Today, transscleral peripheral retina cryotherapy should not be applied as first line treatment, but is often feasible in situations (such as media opacity) that preclude the use of transpupillary photocoagulation and may help to reduce peripheral ischemia in cases of rubeosis iridis if vitrectomy is not indicated for any reason (see Chapter 17).

Cryotherapy of the anterior retina can further be valuable to prevent fibrovascular ingrowth at sclerotomy sites in patients undergoing pars plana vitrectomy (PPV) for proliferative diabetic retinopathy [14]. Peripheral retinal cryotherapy was also suggested in phakic patients with postoperative diabetic vitreous hemorrhage [6]. In these cases, peripheral cryotherapy (often augmented, when possible, by additional posterior pole endolaser photocoagulation) may be used to supplement previous retinal ablative therapy.

15.2.3Cryotherapy for Vascular Abnormalities and Exudative Retinopathies: Coats’ Disease, FEVR and Small Peripheral Hemangiomas

Since the 1970s, photocoagulation has been the first line therapy for vessel abnormalities [11]. Still, in cases with severe exudative detachment, cryotherapy can be advantageous in occluding the pathological vessels. A combination of photocoagulation and cryotherapy should be considered in these patients.

In a series of 117 patients (124 eyes) with Coats’ disease, the primary management was observation in 22 eyes (18 %), cryotherapy in 52 (42 %), laser photocoagulation in 16 (13 %), various methods of retinal detachment surgery in 20 (17 %), and enucleation in 14 (11 %) [10].

Similarly, additional cryotherapy should be used in cases with familial exudative retinopathy when photocoagulation remains insufficient to occlude the pathological vessels (Chapter 22.5).

It is of note that in cases with large subretinal deposits and exudation, repetitive freeze-thaw cycles can be required for effective treatment (Figs. 15.2,

Fig. 15.2. Pigment epithelium and retina 4 weeks after cryocoagulation of the RPE and retina. The outer limiting membrane (large arrows) is ruptured and retinal glial cells interconnect with RPE cells (small arrows). Of note, there is a hyalinization of the retinal vessel walls. (With permission from H. Laqua: Retinale Adhäsionen nach Netzhautoperation. Graefes Archiv klin Exp Ophthalmol 1977; 203:119 – 131)

Fig. 15.3. Pigment epithelium and retina 4 weeks after cryocoagulation of the RPE and retina. While large retinal vessels are still perfused, smaller vessels are obliterated and hyalinized within the scar tissue. (With permission from H. Laqua: Retinale Adhäsionen nach Netzhautoperation. Graefes Archiv klin Exp Ophthalmologie 1977; 203:119 – 131)

15.3), although treatment is limited by its associated inflammation. Cryotherapy may cause an increase in exudation early after treatment. This will usually regress within 2 or 3 weeks after therapy. Only patients with persistent bullous exudation should be watched carefully for retinal breaks and rhegmatogenous detachment.

If the vascular pathology does not regress 4 – 6 weeks after treatment, re-treatment with either cryotherapy or photocoagulation should be considered until the pathological vessels become completely occluded. This will cause secondary regression of exudates, which can take several months.

Cryotherapy is further effective in the treatment of vascular tumors; however, side effects such as increased exudation, hemorrhages and incomplete regression of large tumors should be considered when deciding on cryotherapy as a combined or sole treatment. Small peripheral tumors are most likely to benefit from cryotherapy (see Chapters 28.2 – 28.4).

References

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Core Messages

Vitreoretinal surgery allows the treatment of even advanced proliferative diseases of the retina. Main indications for vitrectomy include the destruction of ischemic retina and pathological vessels, the removal of dense vitreous opacities, the release of retinal traction and retinal detachment repair

Technical prerequisites include vitrectomy in a closed system. Wide-angle viewing systems allow visualization of the peripheral retina during surgery. Endo-photocoagulation facilitates destruction of ischemic retina and abnormal vessels

Silicone oil as an inert tamponade agent may help to prevent growth factor accumulation in the vitreous cavity. Retinal fibrovascular re-pro- liferations are generally based on the remaining posterior vitreous. Chromovitrectomy by triamcinolone acetonide can help to detect vitreous remnants

The iris-lens diaphragm physiologically prevents growth-factor accumulation in the anterior segment and should be maintained if possible. Cataract surgery has certain peculiarities, e.g., a large rhexis is required that facilitates later inspection of the peripheral retina. Silicone lenses should be avoided if future silicone oil surgery is likely

16.1 Introduction

No advance in the treatment of vitreoretinal diseases has been as significant as the introduction of pars plana vitrectomy by Machemer in 1971 [44]. The closed system allowed for a safe intraocular manipulation and constant viewing of the retina. During the past few decades the instrumentation has advanced, but the same principles still apply.

Vitrectomy not only removes opacities but releases vitreoretinal traction. In proliferative disease additional laser photocoagulation of ischemic retina is required. This chapter addresses the indications and surgical techniques.

16.2Prerequisites for Vitreoretinal Surgery in Retinal Vascular Disease: Microscope Requirements and Wide-Angle Viewing Systems

Standard equipment for pars plana vitrectomy includes a vitreous cutter and aspiration device, an infusion of BSS or similar, an air pump, a contact or non-contact viewing system, and a microscope.

The stereo operating microscope should allow a magnification of up to 30-fold. It should be equipped

with coaxial illumination, a power zoom, power focusing, and X-Y positioning. The microscope needs to be fitted with laser filters for both the surgeon and the assistant. An integrated video system serves the purpose of documentation and co-visuali- zation for the personnel or other observers.

The initial visualization in vitrectomy was performed using a hand-held, plano-concave contact lens (e.g., Hoffman or Landers lens), which allowed control of the central fundus. For a better view to the peripheral retina, a biconcave lens is available; however, the viewing angle is limited to 20 – 35 degrees.

Currently, 130-degree wide-angle viewing systems are commonly used.

The inverted image from the wide-angle lens system is corrected through a stereoscopic diagonal inverter. Unless the contact lens is self-stabilizing, a skilled assistant is needed. Non-contact wide-angle systems (e.g. Biom, Oculus, Germany) can be managed by the surgeon alone. A non-contact system is atraumatic to the cornea, yet sufficient visualization of the peripheral retina can still be achieved when rotating the eye.

Table 16.1 lists the currently available wide-angle viewing systems.