Ординатура / Офтальмология / Учебные материалы / Эндокринная офтальмопатия - мультидисциплинарный подход 2007

Table 1. Ophthalmological examination for early detection of DON

Are Additional Investigations Helpful?

Automated perimetry is a necessary investigation for the evaluation of optic nerve function; the most frequent defects being a central scotoma, an arcuate or altitudinal defect, or uniform depression [8]. Pattern reversal visualevoked potential is a complementary study which can identify early optic nerve dysfunction [10]. CT scan or magnetic resonance imaging (MRI) is essential to detect apical crowding and intracranial fat prolapse, which are highly correlated with DON [3, 8] (fig. 1). When at the orbital apex, the perineural fat effacement is greater than 50%, the diagnostic sensitivity and specificity is high (80 and 70.6%, respectively), making it a good diagnostic indicator [11]. However, as noted previously, there are occasional patients who demonstrate clinical evidence of DON without CT evidence of enlarged extraocular muscles or apical crowding of the optic nerve [8, 11].

How Fast Can Dysthyroid Optic Neuropathy Develop?

Is Urgent Treatment Necessary?

Severe GO can develop within hours of a stressful event, such as major surgery. Similar degrees of severity of disease may also be present in patients with a longer history of impairment of colour vision or visual acuity over a

period of months. This is particularly likely in the tight orbit [11] where exophthalmos has not been recognised or eyelid edema has been incorrectly attributed to allergy. In any individual with active disease, the clinician has to assume that disease severity has not yet peaked and could progress rapidly; peak severity of GO follows peak activity. Acceleration of the inflammatory cascades in GO leading to compressive or inflammatory optic neuropathy or corneal exposure necessitates urgent treatment with immunosuppression and/or surgical decompression of the orbit.

Urgent treatment is not necessary if signs of optic nerve impairment are equivocal and the disease activity, as judged by the CAS [12] score, is low. Spontaneous recovery of DON in patients who have refused treatment reminds all clinicians that we are managing a condition with a finite natural history.

What Is the Evidence Base for the Treatment of

Dysthyroid Optic Neuropathy?

Currently, the evidence base for treatment of DON is unfortunately inadequate. The first reason for this is that diagnostic criteria have yet to be established and the distinction between probable and definite DON is not always clear [8]. Secondly, the numbers of patients presenting to individual units is small. This means that randomised controlled treatment trials have not been performed. There is one exception, which is a small but useful trial [13]. Fifteen patients presenting with very active GO and DON were randomised into treatment with high-dose IV steroid or surgical decompression of the orbit. Four of the nine steroid-treated and 5 of the 6 surgical patients had to be switched to the other treatment arm because of a deterioration or failure to improve visual acuity; subsequently they improved. The results favoured initial treatment with high-dose IV steroids rather than initial surgical decompression. Anecdotal evidence [14] suggests that addition of ciclosporin to pulsed intravenous steroid is needed in order to avoid surgery. Orbital radiotherapy is frequently used as an adjunctive treatment but it should be avoided in diabetics and those under 35 years of age [15]. Use of orbital decompression surgery or an alternative immunosuppressant does reduce the total steroid dose and the incidence of steroid-induced side effects including orbital Cushing’s syndrome [16].

What Is the Role of Surgery in Dysthyroid Optic Neuropathy?

Most cases of DON are due to apical optic nerve compression by enlarged extra-ocular muscles. Surgical expansion of the orbital apex by orbital decompression

Table 2. Advantages and disadvantages of orbital decompression surgery for DON

Advantages

(1)Immediate reduction in apical compression of the optic nerve

(2)Reduction in need for long-term steroid treatment

(3)Reduction in corneal exposure, if present

(4)Reduction in orbital venous pressure, reducing intraocular pressure and congestion of conjunctiva and caruncle

Disadvantages

(1)Surgical procedure necessitates general anaesthetic

(2)Risk of orbital haemorrhage, visual loss, diplopia, infraorbital hypoaesthesia, sinusitis (late or early) and CSF leak

is an effective method of immediate reduction of pressure on the optic nerve (fig. 1). Usually removal of the ethmoids is sufficient, but in rare cases removal of the anterior-lateral wall of the sphenoid sinus is necessary [17]. Surgery does have a long-term beneficial effect [18]. The advantages and disadvantages of surgery are listed in table 2.

How Many Patients Become Blind due to

Dysthyroid Optic Neuropathy?

Blindness has been reported in 5 of 305 cases with DON despite surgery, steroids and radiotherapy [18]. Earlier recognition of GO, an appreciation of the importance of stable thyroid function and more effective immunosuppression and surgery apparently have reduced the incidence of blindness due to DON. Late diagnosis can still result in blindness, particularly if visual loss is incorrectly attributed to another cause, such as cataract. Corneal ulceration due to exophthalmos can also cause blindness even if there is no neuropathy.

References

1Wiersinga WM, Bartalena L: Epidemiology and prevention of Graves’ ophthalmopathy. Thyroid 2002;12:855–860.

2Feldon S, Muramatsu MS, Weiner JM: Clinical classification of Graves’ ophthalmopathy Indication of risk factors for optic neuropathy. Arch Ophthalmol 1984;102:1469–1472.

3Birchall D, Goodall KL, Noble JL, Jackson A: Graves ophthalmopathy: intracranial fat prolapse on CT images as an indicator of optic nerve compression. Radiology 1996;200:123–127.

4Dosso A, Safran AB, Sunaric G, Burger A: Anterior ischemic optic neuropathy in Graves’ disease. J Neuroophtalmol 1994;14:170–174.

5Koornneef L, Schmidt ED, Van der Gaag R: The orbit: structure, autoantigens, and pathology; in

Wall J, How J (eds): Graves’ Ophthalmopathy. Oxford, Blackwell Scientific Publications, 1990, vol 26, pp 1–21.

6Kalman R, Mourits MP: Diabetes mellitus: a risk factor in patients with Graves’ ophthalmopathy. Br J Ophthalmol 1999;83:463–465.

9Trobe JD: Optic nerve involvement in dysthyroidism. Ophthalmology 1981;88:388–392.

10Tsaloumas MD, Good PA, Burdon MA, Misson GP: Flash and pattern visual evoked potentials in the diagnosis and monitoring of dysthyroid optic neuropathy. Eye 1994;8:638–645.

11Neigel JM, Rootman J, Belkin RI, Nugent RA, Drance SM, Beattie CW, Spinelli JA: Dysthyroid optic neuropathy: the crowded orbital apex syndrome. Ophthalmology 1988;95:1515–1521.

12Mourits MP, Koorneef L, Wiersinga WM, Prummel MP, Berghout A, van der Gaag R: Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: a novel approach. Br J Ophthalmol 1989;73:639–644.

13Wakelkamp IM, Baldeschi L, Saeed P, Schlingemann RO, Verbraak FO, Blank LE, Prummel MF, Wiersinga WM: Surgical or medical decompression as a first-line treatment of optic neuropathy in Graves’ ophthalmopathy? A randomized controlled trial. Clin Endocrinol 2006;65:132.

14Meyer PA: Avoiding surgery for thyroid eye disease. Eye 2006;10:1171–1177.

15Wakelkamp IM, Tan H, Saeed P, Schlingemann RO, Verbrakk FD, Blank LE, Prummel MF, Wiersinga WM: Orbital irradiation for Graves’ ophthalmopathy: is it safe? A long-term follow-up study. Ophthalmology 2004;111:1557–1562.

16Boschi A, Detry M, Duprez T, Rolland F, Plas B, De Plaen J, Eloy P: Malignant bilateral exophthalmos and secondary glaucoma in iatrogenic Cushing’s syndrome. Ophthalmic Surg Lasers 1997;28:318–320.

17Gormley PD, Bowyer J, Jones NS, Downes RN: The sphenoid sinus in optic nerve decompression. Eye 1997;11:723–726.

18Warren JD, Spector JG, Burde R: Long term follow-up and recent observations on 305 cases of orbital decompression for dysthyroid optic neuropathy. Laryngoscope 1989;99:35–40.

Prof. Antonella Boschi

Department of Ophthalmology, St. Luc University Hospital Avenue Hippocrate, 10

BE–1200 Brussels (Belgium)

Tel. 32 2764 1950, Ext. 1985, Fax 32 2764 29 88, E-Mail boschi@ofta.ucl.ac.be

What Are the Steps and Timing of Rehabilitative Surgery?

During the post-inflammatory phase of GO, after a 6- to 8-month period of stable endocrinological and ophthalmic clinical picture, surgical rehabilitation can be performed if required. Depending on the severity of the disease surgical rehabilitation can be more or less extensive, the full treatment consisting of decompression surgery, squint surgery, eyelid lengthening, blepharoplasty and eyebrow plasty.

The first rehabilitative step mainly consists of orbital bony decompression and early intervention soon after stabilisation had been advocated [2]. Fibrosis due to long-lasting orbital disease or as a possible consequence of retrobulbar irradiation administrated in the early phase of GO has been questioned to be a possible cause of poor distensibility and plasticity of the soft orbital tissues resulting in scarce effectiveness of orbital expansion surgery [3–6]. Recent studies, however, have demonstrated that long-lasting GO or pre-operative radiotherapy do not adversely interfere with the results of orbital bony decompression; thus, when the stabilisation of Graves’ disease and orbitopathy has occurred, rehabilitative surgery can be started at any time and no adverse effects from common preceding treatments such as retrobulbar irradiation are to be expected [7, 8].

Decompression surgery causes a reduction of exophthalmos as well as reduction of upper and lower eyelid displacement [7]. It may positively influence extra-ocular muscle restriction, but displacement of the soft orbital tissues caused by decompression procedures may also cause strabismus. Eventual squint surgery should therefore follow orbital decompressions but considering that vertical tropias may influence eyelid position, squint surgery should precede eventual correction of eyelid position. Finally, when necessary the finishing touch can be given by blepharoplasty and eyebrow plasty.

In short, surgical rehabilitation needs to respect the given order since the preceding step may influence the step that follows. When all the steps are necessary the entire rehabilitation may require between 1.5 and 2 years. In particular cases, exceptions are possible and the rehabilitation can be favourably sped-up by carrying out more than one procedure at the same time.

How Should Patients Be Selected for Rehabilitative Surgery

Patients should be selected on the basis of their motivation to undertake a long-lasting, potentially risky, and somewhat exhausting trail. Multiple interventions may also be necessary in the case that full treatment, starting with orbital decompression, is not required. Patients should be fully aware of the risks and benefits of each possible procedure and should accept the possibility

of partial results or temporary worsening of their inability to function in the course of rehabilitation. Information provided by the physicians, although precise, may be inadequate to the patients and potential candidates for surgery can better build up realistic expectancies by contact with patient associations. The psychological impact of GO on the affected patient is consistent but should not itself be a reason to undertake a surgical treatment with potential distressing effects in the same respect. It is up to the physician to understand when the patient has matured the necessary acquisition of consciousness for being admitted to surgical rehabilitation, and the ophthalmologic controls necessary to assess disease stability should also be finalised according to this.

Besides the patient’s determination to accept major surgeries, the possibility to aim at attaining only partial results should always be weighed in the light of patients’ characteristics such as age, general health conditions, profession, education and psyco-social environment. Often conservative surgery is of maximal benefit to the patient in spite of modest final results that may be unattractive to the surgeon.

References

1Terwee CB, Dekker FW, Prummel MF, Wiersinga WM: Graves’ ophthalmopathy through the eyes of the patient: a state of the art on health-related quality of life assessment. Orbit 2001;20:281–290.

2Härting F, Koornneef L, Peeters HJF, Gillisen JPA: Fourteen years of orbital decompression in Graves’ disease: a review of technique, results and complications. Orbit 1986;5:123–129.

3Wilson WB, Manke WF: Orbital decompression in Graves’ disease: the predictability of reduction of proptosis. Arch Opthalmol 1991;109:343–345.

4Goldberg RA, Weinberg DA, Shorr N, Wirta D: Maximal three-wall orbital decompression through a coronal approach. Ophthalmic Surg Lasers 1997;28:832–843.

5Kazim M, Trokel S, Moore S: Treatment of acute Graves’ orbitopathy. Ophthalmology 1991;98:

1443–1448.

6Clauser L, Galie M, Sarti E, Dallera V: Rationale of treatment in Graves’ ophthalmopathy. Plast

Reconstr Surg 2001;108:1880–1894.

7Baldeschi L, Wakelkamp IMMJ, Lindeboom R, Prummel MF, Wiersinga WM: Early versus late orbital decompression in Graves’ orbitopathy: a retrospective study in 125 patients. Ophthalmology 2006;113:874–878.

8Baldeschi L, MacAndie K, Koetsier E, Blank L, Wiersinga WM: The influence of previous orbital irradiation on the outcome of rehabilitative decompression surgery in Graves’ orbitopathy. Am J Ophthalmol, in press.

Dr. Lelio Baldeschi

Room D2–436, Orbital Center, Department of Ophthalmology Academic Medical Center, University of Amsterdam Meibergdreef 9

NL–1105 AZ Amsterdam (The Netherlands)

Tel. 31 20 566 3580, Fax 31 20 566 9053, E-Mail l.baldeschi@amc.uva.nl

Fig. 1. A patient with severe GO and optic neuropathy unresponsive to glucocorticoids and orbital irradiation. a At admittance for orbital decompression. b 6 months after extensive three-wall orbital decompression performed through a combined transinferior conjunctival fornix and coronal approach. Visual function was restored and disfigurement treated.

Functional Aims

According to a large retrospective study decompression surgery can offer a rapid solution to dysthyroid optic neuropathy with an acceptable list of adverse effects (fig. 1) [4]. A more recent randomised controlled clinical trial comparing surgical to medical decompression as a first-line treatment of dysthyroid optic neuropathy led to the conclusion that immediate decompression surgery did not result in a better outcome in terms of increase in visual acuity and therefore intravenous followed by oral glucocorticoids appeared to be the firstchoice therapy [5]. In line with these latter results, it was also the trend of clinicians of three European professional organisations potentially involved in the treatment of patients with GO, who answered a questionnaire sent by the European Group on Graves’ Orbitopathy (EUGOGO) [6, 7].

In GO exophthalmos, increased palpebral fissure width, blink rate alterations, lid lag, lagophthalmos, deficit of elevation and poor Bell’s phenomenon can all be potentially connected with drying of the ocular surface. In the course of active GO, ocular surface damage correlated significantly with a reduced tear secretion due to autoimmune lacrimal gland impairment, but not with increased ocular surface or impaired upgaze [8]. Other studies had shown that in patients with short duration of GO tear secretion was not abnormal and exophthalmos, lid lag and lagophthalmos did not correlate with ocular surface

damage, while the damage to the ocular surface depended principally on widened palpebral fissure which is the cause of increased ocular surface evaporation resulting in an elevated tear film osmolarity similar to that of sicca kerato-conjunctivitis [9]. The influence of decompression rehabilitative surgery on increased eyelid aperture has recently been reported. A decrease in eyelid aperture based equally on decreased upper and lower lid displacement was found in about 50% of the patients presenting with preoperative increased eyelid aperture and decompressed by means of a 3-wall coronal approach which leaves the upper and lower lid retractors undisturbed [10].

The effect of decompression surgery on severe corneal alteration had never been studied specifically and although most of the studies on orbital decompression report a reduction in symptoms associated with exposure keratopathy, a case of severe corneal ulcer refractory to decompression surgery has also been published [11].

Eyeball subluxation is a rare (0.1%), recurrent complication of GO that deserves urgent referral to a specialist centre as it represents a potential cause of visual loss [2, 12]. In light of the current literature, eyeball subluxation seems to occur in the type I, ‘lipogenic’ variant of GO as described by Nureny and never in the type II ‘myopathic’ variant. Globe subluxation in fact requires extensibility of the extraocular muscles [2, 13]. For this, it is conceivable that a definitive treatment of this sight-threatening condition can benefit either from bony and/or orbital fat decompression, but studies addressing this issue are missing.

Among patients with inactive congestive orbitopathy there appear some with borderline optic nerve perfusion: a blood flow that is just able to maintain neural function. Such patients would seem to be liable to visual obscuration whenever there is a fall in systemic blood pressure due to postural changes, diabetics appearing particularly susceptible to this phenomenon. The vascular embarrassment of the optic nerve depending on elevated intraorbital pressure is very effectively relieved by orbital decompression and leads to an immediate cessation of postural visual obscuration [3].

Organised choroidal fold consecutive to eyeball indentation by enlarged extraocular muscles had been thought to be refractory to orbital decompression [14] until recently when a positive response of this complication to bony decompression surgery has been reported [15].

Rehabilitative Symptomatic Aims

In GO, severe functional complications due to increased intraocular pressure are rare, different degrees of venous congestion, strabismus, eyelid puffiness and retraction, exophthalmos and symptoms such as retroocular pressure and/or grittiness due to chronic corneal exposure are more frequent. Decompression surgery is the mainstay method to treat stable disfiguring