Sektion dog-uveitis anschreiben

L o n g t e r m r e s u l t s o f p a r s p l a n a v i t r e c t o m y i n
t h e m a n a g e m e n t o f i n t e r m e d i a t e u v e i t i s
A. Heiligenhaus *#, N. Bornfeld#, A. Wessing#,
*Department of Ophthalmology, at St. Franziskus Hospital, Muenster
#Department of Ophthalmology, University of Essen
R a t i o n a l e f o r v i t r e c t o m y i n i n t e r m e d i a t e u v e i t i s
Following the first observations by Diamond and Kaplan (1978) [1] the efficacy of pars
plana vitrectomy in eyes with chronic and recurrent intermediate uveitis has been studied
repeatedly. The instantaneous benefit from surgery is an increase in vision related to the
removal of vitreal flare or to lensectomy [1, 2, 3]. Further indications to vitrectomy are the
vitreous hemorrhages, PVR with retinal detachment, and persistent hypotony [2, 4]. Several
previous studies have shown that vitrectomy may lead to a decreased incidence and severity
of recurrences in patients not responding sufficiently to corticosteroids or cryotherapy [2, 5--
7]. However, the longterm effect of vitrectomy on the course of the inflammatory disease is a
matter of debate. It has been postulated that the persistent effect of vitrectomy may be caused
by the removal of inflammatory components and growth factors within the vitreous, or by the
removal of mechanical factors provoking macular edema, or by achieving a better penetration
of antiinflammatory drugs or inhibitory factors to the site of inflammation.
Our current understanding of the immunological mechanisms in intermediate uveitis is
incomplete which is related to the inaccessibility of the tissue involved. Experimental data
have provided convincing evidence that the chronic posterior uveitis presenting as retinal
vasculitis, focal chorioretinal infiltrates and vitritis is compassing characteristics similar to
autoimmune diseases [reviewed in 8, 9]. The restricted autoreactive inflammatory cell
repertoire at the site of active posterior uveitis in the early disease may be followed by a
heterogeneous cell response. This is one of the reasons that previous studies of vitreal or
chorioretinal specimen harvested from patients with advanced uveitis have not yielded the
information neccessary to characterize the initiating disease process in great detail. A spill of
migratory cells from the eye may allow to screen the disease activity by screening the
peripheral blood lymphocytes [10]. However, the local cytokine environment is especially
critical for the regulation of the inflammatory processes. Both, Th1 and Th2 related cytokines
were present in the inflamed tissue in expermimental posterior uveitis [11]. As a consequnce
from the above mentioned experimental data, future treatment modalities targeting the T cell
receptor/major histocompatibility complex/antigen-binding, the CD4+ T cells, and the
cytokines may be a breakthrough. Furthermore, mucosal tolerance induction which has been
shown to improve the clinical course of certain other autoimmune diseases is a promising
novel approach [reviewed in 8, 9]. The fact that current medical treatment is nonspecific, has
limited efficacy with recurrencies dispite treatment, and often is followed by a number of
unwarrented side effects has stimulated the physicians to search for alternatives, including
certain surgical approaches.
T h e r a p y o f i n t e r m e d i a t e u v e i t i s a n d i n d i c a t i o n s
f o r v i t r e c t o m y
The therapeutic approach is dependent on the individual course of the disease. Mild
disease activity may spontaneously improve and does not necessarily justify treatment. When
therapy is required, a therapeutical stepladder approach has been suggested, consisting of I.
antiinflammatory
cryotherapy,
vitrectomy,
systemic
immunosuppression. Since intermediate uveitis in common is limited in duration, the principal
goal of treatment is to avoid vision threatening complications.
The usefulness of nonsteroidal antiinflammatory drugs for the treatment of posterior
uveitis has not been convincingly supported by prospective, randomized, double blind studies.
However, many uveitis experts feel that this group of medication is helpful for treating
patients with moderately active intermediate uveitis.
The efficacy of corticosteroids has been repeatedly demonstrated. The results of orbital
floor steroid injections to 33 eyes with various uveitic diseases were analyzed [12] with
regard to the visual acuity and vitreous cellular activity. An improvement with an average
duration of effect of 9 weeks was obtained in nearly 50% of injections. This is comparing
favourable with the results of systemic immunosuppression. However, the response to one
particular injection could not be predicted by the reponse to previous or to subsequent
injections to the same eye indicating that repeated trials are justified. Periocular steroids may
also be helpful in the treatment of cystoid macular edema (CME) [13]. Another recent study
showed a 60% success rate in visual outcome at 12 year in posterior uveitis patients managed
on corticosteroids alone, improving to 77% with additional other immunosuppression.
Treatment was started with =1mg/kg prednisolone and was continued in high dosages
(=40mg) for at least 5 weeks. However, side effects from steroids were noted in 50% of the
patients [14], which is frightening in view of the chronic course in many of the cases with
posterior uveitis. For this reason, intravitreal sustained release corticosteroid devices may be
effective while preventing the harmful systemic side effects. The first experimental studies
suggested that biologically effective intraocular concentrations may be released into the eye
for several months. By intravitreal dexamethasone devices, experimental uveitis in New
Zealand rabbits was significantly improved with regard to the clinical signs, the histological
tissue damage, the aqueous protein concentration and aqueous white blood cells [15].
Cryocoagulation in uveitic eyes is controversial, and may be particularly helpful in cases
which are resistant to corticosteroids and develop active neovascularization of the vitreous
base [16]. Since active retinal neovascularization has a high rate of secondary complications,
cryocoagulation has been advocated in these conditions. The longterm effect on the
inflammation and on the cystoid macular edema, however, is not clear.
L o n g t e r m e f f e c t o f v i t r e c t o m y
The major rationale for performing pars plana vitrectomy in uveitis is the removal of
significant media opacities. There is compelling evidence from various previous studies that
the visual acuity may increase and remain stable after removal of vitreous infiltrations or lens
opacities. Whether to do cataract extraction alone or combined with vitrectomy is still a
matter of controversy. In cases with significant amounts of vitreal infiltration, combined
cataract surgery and vitrectomy have been preferred. Also, intraocular lens implantation in
chronic uveitis remains controversial. The longterm results after lens implantation may only be
favourable when inflammation is abolished by appropriate immunosuppession. Otherwise, the
course may be complicatied by severe uveitic episodes, recurrent capsular opacifications,
severe iridocyclitic membranes, hypotony, profound PVR and hemorrhages in the anterior
chamber or vitreous.
The longterm results after vitrectomy in uveitis patients and reattachment of
simultaneously detached retina or removal of epiretinal membranes generally were satisfactory
by anatomical means. However, the improvement in vision was restricted by the unfortunate
primary damage to the retina in various cases. In addition, the surgical removal of cyclitic
membranes causing ciliary traction has been repeatedly suggested as beeing benefitial for a
longterm stabilization of persistent hypotony.
The influence of vitrectomy in uveitis patients on the course of the underlying disease
process is not well defined. Recent experimental data are suggesting that the persistence of
the vitreous is associated with the reactivation of a secondary immune response.
Consequently, the removal of the vitreous may have a favourable influence on the subsequent
uveitis course. Also, the timing of surgery is discussed controversely. Some authors have
recommended to do vitrectomy immediately when topical or systemic corticosteroids failed
[17]. A decrease in both the recurrence of disease and the need for immunosuppressive
medication after pars plana vitrectomy has been noted recently [18]. This is in agreement with
previous observations that vitrectomy may reduce the inflammatory activity postoperatively,
and may allow to taper the immunosuppressive medication in certain cases. Correspondingly,
these authors are suggesting to perform vitrectomy if loss of vision is progressive or
prolonged corticosteroid therapy fails. Surgery, in conclusion, may be warranted to prevent
the development of irreversible anatomical damages to the retina.
However, others are advocating to delay surgery. These authors are referring to the
possible complications of vitrectomy which have in some cases been substantial and have to
be considered in every single case. The most common complication was cataract formation.
Others were vitreous hemorrhages, tractional retinal detachment, rhegmatogenous retinal
detachment, proliferative vitreoretinopathy, and glaucoma. Altogether, these were
occasionally requiring additional surgery.
Regardless of the timing of vitrectomy in uveitis, the preoperative control of intraocular
inflammation is vital in all patients. It is important in this regard that postoperative disease
recurrence has been observed especially in patients not beeing on perioperative
immunosuppression or having active inflammation at the time of surgery. Futhermore, active
uveitis is a risk factor for the development of severe postoperative PVR [19]. The
angiogenetic activity of inflamed vitreous is supported by the observation that vitreous extract
obtained from rabbit eyes with endotoxin-induced uveitis may induce severe
neovascularization. This harmful effect has been attributed to the prostaglandin E2 and
leukotriene B4 [20].
Cystoid macular edema accounts for visual impairment in a majority of patients with
chronic uveitis. CME may resolve with posterior subtenon injections of depot corticosteroid
injections when given before irreversible macular degeneration develops or before vision
decreases below 20/60 [13]. It has been recently shown that vitrectomy may have a beneficial
effect on cystoid macular edema in uveitis patients not responding to steroid treatment. While
64% of the cases improved by vitrectomy, 18% worsened in this preliminary study [21],
which is in correspondance to the findings of others. The individual response to vitrectomy
has not been reliably predictable by any preoperative test. Unfortunately, no general
recommendation can be drawn from the recent studies with regard to the role of vitrectomy in
treating CME or in inducing CME in each individual case.
1. Diamond JG, Kaplan HJ: Lensectomy and vitrectomy for complicated cataract secondary to
uveitis. Arch Ophthalmol 1978, 96: 1798--1804.
2. Diamond JG, Kaplan HJ: Uveitis: effect of vitrectomy combined with lensectomy.
Ophthalmology 1979, 86: 1320-1327.
3. Nobe JR, Kokoris N, Diddie KR, Cherney EF, Smith RE: Lensectomy-vitrectomy in
chronic uveitis. Retina 1983, 3: 71--76.
4. Nolthenius PA, Deutman AF: Surgical treatment of the complications of chronic uveitis.
Ophthalmologica 1983, 186: 11-16.
5. Klöti R: Pars plana Vitrektomie bei chronischer Uveitis. Klin Mbl Augenheilk 1988, 192:
425--429.
6. Heimann K, Schenke L, Brunner R, Amerian B: Pars plana vitrectomy in the treatment of
chronic uveitis. Dev Ophthalmol 1992, 23: 196--203.
7. Heiligenhaus A, Bornfeld N, Foerster MH, Wessing A: Long term results of pars plana
vitrectomy in the management of complicated uveitis. Br J Ophthalmol 1994, 78: 549--
8. Dick AD, Cheng YF, Liversidge J, Forrester JV: Immunomodulation of experimental
autoimmune uveoretinitis: a model of tolerace induction with retinal antigens. Eye 1994,
8: 52--59.
9. Dick AD: Experimental approaches to specific immunotherapies in autoimmune disease:
future treatment of endogenous posterior uvitis? Br J Ophthalmol 1995, 79: 81--88.
10. Feron EJ, Calder VL, Lightman SL: Oligoclonal activation of CD4+ T lymphocytes in
posterior uveitis. Clin Exp Immunol 1995, 99: 412--418.
11. Barton K, Lightman S: T lymphocyte effector mechanisms in the retina in posterior
uveitis. Eye 1994, 8: 60--65.
12. Riordan-Eva R, Lightman S: Orbital floor steroid injections in the treatment of uveitis.
Eye 1994, 8: 66--69.
13. Yoshikawa K, Kotake S, Ichiishi A, Sasamoto Y, Kosaka S, Matsuda H: Posterior sub-
tenon injections of repository corticosteroids in uveitis patients with cystoid macular
edema. Jpn J Ophthalmol 1995, 39: 71--76.
14. Howe LJ, Stanford MR, Edelstein C, Graham EM: The efficacy of systemic
corticosteroids in sight-threatening retinal vasculitis. Eye 1994, 8: 443--447.
15. Cheng CK, Berger AS, Pearson PA, Ashton P, Jaffe GJ: Intravitreal sustained-release
dexamethasone device in the treatment of experimental uveitis. Invest Ophthalmol Vis
Sci 1995, 36: 442--453.
16. Devenyi RG, Mieler WF, Lambrou FH, Will BR, Aaberg TM: Cryopexy of the vitreous
base in the management of peripheral uveitis. Am J Ophthalmol 1988, 106: 135--138.
17. Kroll P, Romstöck F, Grenzebach UH, Wiegand W. Frühvitrektomie bei endogener
juveniler Uveitis intermedia - Eine Langzeitstudie. Klin Monatsbl Augenheilk 1995, 206:
246--249.
18. Schönfeld CL, Weißschädel S, Heidenkummer HP, Kampik A: Vitreoretinal surgery in
intermediate uveitis. Ger J Ophthalmol 1995, 4: 37--42.
19. Girard P, Mimoun G, Karpouzas I, Montefiore G: Clinical risk factors for proliferative
vitreoretinopathy after retinal detachment surgery. Retina 1994, 14: 417--424.
20. Naveh N, Nussbaum A, Desatnik H, Bartov E: Angiogenic activity of vitreous extract
obtained from rabbit eyes with endotoxin-induced uveitis. Ophthalmic Res 1995, 27: 23-
21. Dugel PU, Rao NA, Ozler S, Liggett PE, Smith RE: Pars plana vitrectomy for intraocular
inflammation-related cystoid macular edema unresponsive to corticosteroids. A
preliminary study. Ophthalmology 1992, 99: 1535--1541.

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