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

Table 2. GO-QoL scores before, during and after treatment of GO [10–12]

visual functioning and 0.87 for appearance. Older patients and patients with more severe eye motility disturbances reported more problems with visual functioning, and females reported more with appearance, further supporting the construct validity. Like the general HRQL measurements using the MOS, the GO-QoL scores correlated only moderately with clinical measurements of severity and activity of GO. In a test-retest reliability study, substantial intraclass correlation coefficients of 0.80 were found for both subscales of the GO-QoL, indicating the subscales differentiate well between patients with different degrees of functioning [11].

The GO-QoL questionnaire thus seems to be valid (as judged from its construct validity it actually measures what it is supposed to measure) and reliable (as judged from its accuracy reflected by the small measurement error and from its reproducibility). The Go-QoL is now available in six languages (Dutch, English, French, German, Greek and Italian) and can be downloaded for free from the website (www.eugogo.com).

What Are the Results of the GO-QoL?

Table 2 shows the GO-QoL scores obtained in cross-sectional studies of Dutch patients before, during and after treatment of GO [10–12]. Because the GO-QoL specifically measures limitations in functioning as a result of GO, healthy subjects should score 100 points (no limitations). It is clear that QoL is severely impaired in untreated patients, and not fully restored after treatment. The scores obtained in the untreated Dutch patients are in good agreement with those in Australian patients using a slightly modified GO-QoL (59.0 for visual functioning and 54.4 for appearance) [13].

Can You Explain Response Shift in Quality of Life?

HRQL measures can be important indicators of treatment success. However, HRQL measures incorporate the effects of adaptation to the illness

that happens over time. HRQL is a dynamic construct, which means that a person’s ideas about poor functioning and general health can change over time as a consequence of coping strategies, seeking social support, changing expectations, etc. For example, patients with physical disabilities, e.g. spinal cord injuries, may place greater emphasis on mental abilities and selectively focus on aspects that make them appear better off than other people (‘brain is more important than brawn’). These changes are inherent to the process of adjustment to the illness and are called response shift [14].

Response shift can interact with the effects of treatment, raising questions on the validity of within-subject comparison of changes in HRQL scores over time. Alternatively, response shift can be viewed as an adoptive characteristic of the individual, changing certain patient outcome levels in the HRQL model (fig. 1) while other levels remain stable. There is no consensus how to deal with response shift. One can argue that response shift is not a bias but a determinant of a reported change in HRQL. It can either be considered as part of the intervention strategy (active) or natural adaptation process (passive).

Can GO-QoL Be Used as a Separate Outcome

Measurement in GO?

Assessment of therapeutic outcome in GO patients is usually done by quantitative measurements of severity (lid aperture, proptosis, etc.) and activity (CAS). However, the primary goal of treatment is to improve functioning and general health, and consequently therapeutic outcome should also be evaluated in terms of functioning and general health perceptions (that is by HRQL). In other words, treatments should not only work from the physician’s perspective, but they should also help from the patient’s perspective. In 1992, the four international thyroid associations endorsed a joint statement that patient self-assessment should be included in the evaluation of treatment effects [15]. The GO-QoL was specifically designed for patient self-assessment and is recommended as a separate outcome measurement, especially in clinical trials [16].

In a prospective study patients completed the GO-QoL questionnaire before and three or six months after treatment, depending on the procedure (table 3) [17]. The direction and amount of change in GO-QoL scores on visual functioning or appearance after different treatments were in accordance with our pre-specified hypotheses about treatment effects (except for changes after eye muscle surgery, possibly related to improvement of diplopia in only 50% of patients in this series). Effect sizes in the GO-GoL subscales were higher than effect sizes of general HRQL subscales (like SF-36, SIP), supporting the longitudinal validity of the GO-QoL.

Table 3. GO-QoL scores for visual functioning (VF) and appearance (AP) in patients with GO before and after specific eye treatment

Scales on which treatment was expected to have the highest effect are shown in bold figures. NS Not significant. Effect size Mean change divided by SD of pre-treatment score.

A clinical response to treatment was associated with an increase in GO-QoL scores of approximately 10–20 points after major treatments (radiotherapy or decompression) and of 3–10 points after minor surgery (eye muscle and eye lid surgery). The minimal clinically important difference (MCID) in either GO-QoL subscale appeared to be 6–10 points (the MCID has been defined as the smallest difference in score on the domain of interest which patients perceive as benefit and which would mandate, in the absence of troublesome side effects and costs, a change in the patient’s management). One could consider a mean change of at least 6 points on one or both GO-QoL subscales an important change in daily functioning for GO patients. For more invasive therapies, a change of at least 10 points is recommended as MCID.

Is Quality of Life Fully Restored after Treatment of GO?

After a median follow-up of 10 years of 120 GO patients, 32% of patients reported that their eyes still did not appear normal, and 28% were not satisfied with the appearance of their eyes [18]. Similar findings are reported applying HRQL questionnaires in 163 GO patients at a median of 11.7 years after treatment [12]. GO-QoL scores were 23.5 points higher on visual functioning and

clinical oncology practice facilitates the discussion of HRQL issues, resulting in benefits for patients by improving their QoL and emotional functioning [21, 22]. In GO patients, psychosocial morbidity and especially emotional distress are frequently present; HRQL questionnaires could identify patients who are in need of further counselling, as recommended by several authors [8, 9, 13].

References

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2Prummel MF, Mourits MP, Blank L, Berghout A, Koornneef L, Wiersinga WM: Randomized double-blind trial of prednisone versus radiotherapty in Graves’ ophthalmopathy. Lancet 1993;342: 949–954.

3Wilson IB, Cleary PD: Linking clinical variables with health-related quality of life. JAMA 1995;273:59–65.

4Terwee 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:

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6Kahaly GJ, Hardt J, Petrak F, Egle UT: Psychosocial factors in subjects with Graves’ ophthalmopathy. Thyroid 2002;12:237–239.

7Elberling TV, Rasmussen AK, Fedt-Rasmussen U, Hording M, Perrild H, Waldemar G: Impaired health-related quality of life: a prospective study. Eur J Endocrinol 2004;151:549–555.

8Kahaly GJ, Petrak T, Hardt J, Pitz S, Egle UT: Psychosocial morbidity of Graves’ orbitopathy. Clin Endocrinol 2005;63:395–402.

9Farid M, Roch-Leveq A-C, Levi L, Brody BL, Granet DB, Kikkawa DO: Psychological disturbances in Graves’ ophthalmopathy. Arch Ophthalmol 2005;123:491–496.

10Terwee CB, Gerding MN, Dekker FW, Prummel MF, Wiersinga WM: Development of diseasespecific quality of life questionnaire for patients with Graves’ ophthalmopathy: the GO-QoL. Br J Ophthalmol 1998;82:773–779.

11Terwee CB, Gerding MN, Dekker FW, Prummel MF, van der Pol JP, Wiersinga WM: Test-retest reliability of the GO-QoL: a disease-specific quality of life questionnaire for patients with Graves’ ophthalmopathy. J Clin Epidemol 1999;52:875–884.

12Terwee CB, Wakelkamp I, Tas S, Dekker F, Prummel MF, Wiersinga WM: Long-term effects of Graves’ ophthalmopathy on health-related quality of life. Eur J Endocrinol 2002;146:751–757.

13Park JJ, Sullivan TJ, Mortimer RH, Wagenaar M, Perry-Keene DA: Assessing quality of life in Australian patients with Graves’ ophthalmopathy. Br J Ophthalmol 2004;88:75–78.

14Terwee CB, Dekker FW, Wiersinga WM, Prummer MF, Bossuyt PM: On assessing responsiveness of health-related quality of life instruments: guidelines for instrument evaluation. Qual Life Res 2003;12:349–362.

15European, American, Latin-American, Japanese and Asia-Oceania Thyroid Associations: Classification of eye changes of Graves’ disease. Thyroid 1992;2:235–236.

16The European Group on Graves’ Orbitopathy (EUGOGO): Clinical assessment of patients with Graves’ orbitopathy: the European Group on Graves’ Orbitopathy recommendations to generalists, specialists and clinical researchers. Eur J Endocrinol 2006;155:387–389.

17Terwee CB, Dekker FW, Mourits MP, Gerding MN, Baldeschi L, Kalmann R, Prummel MF,

Wiersinga WM: Interpretation and validity of changes in scores on the Graves’ ophthalmopathy quality of life questionnaire (GO-QoL) after different treatments. Clin Endocrinol 2001;54: 391–398.

18Bartley GB, Fatourechi V, Kadrmas EF, Jacobson SJ, Hstrup DM, Garrrity JA, Gorman CA: Longterm follow-up of Graves’ ophthalmopathy in an incidence cohort. Opthalmology 1996;103: 958–962.

19Sprangers MAG, de Regt EB, Andries F, van Agt HME, Bijl RV, Boer JB, Foets M, Hoeymans N, Jacobs AE, Kempen GJJM, Miedema HS, Tijhuis MAR, de Haes HCJM: Which chronic conditions are associated with better or poorer quality of life? J Clin Epidemiol 2000;53:895–907.

20Fayers P, Bjordal K: Should quality-of-life needs influence resource allocation? Lancet 2001; 357:978.

21Detmar SB, Muller MJ, Schornagel JH, Wever LDV, Aaronson NK: Health-related quality-of-life assessments and patient-physician communication. A randomized controlled trial. JAMA 2002; 288:3027–3034.

22Velikova G, Booth L, Smith AB, Brown PM, Lynch P, Brown JM, Selby PJ: Measuring quality of life in routine oncology practice improves communication and patient well-being: a randomized contolled trial. J Clin Oncol 2004;22:714–724.

Prof. Wilmar M. Wiersinga

Department of Endocrinology and Metabolism, Academic Medical Centre Room F5–171, University of Amsterdam

Meibergdreef 9

NL–1105 AZ Amsterdam (The Netherlands)

Tel. 31 20 566 6071, Fax 31 20 691 7682, E-Mail w.m.wiersinga@amc.uva.nl

limited only to the right lobe. 123I-scintigraphy showed a homogenous, severalfold increased uptake of the radionuclide in the right lobe of the thyroid gland, whereas the uptake in the left lobe did not differ from the uptake in normal controls. Cytology of the fine-needle aspirate of the right lobe revealed a remarkable inflammatory background mainly by presence of lymphocytes, a finding which was not seen in the cytology of the left lobe. Furthermore, both serum antibodies to TSH receptors and thyroid peroxidase were significantly increased. Consequently, hyperthyroidism of Graves’ disease with involvement of only one lobe of the thyroid gland was diagnosed.

GO is the most common cause of both unilateral and bilateral proptosis in adults [2–8, 22, 23]. The literature about real unilateral GO is relatively scarce and heterogeneous. However, to date there are no conclusive data and explanations for unilateral GO. Sattler [9] and others have noted more prominent orbital findings on the ipsilateral side of prominent thyroid enlargement in cases of asymmetric thyroid gland swelling, but this thyroid abnormality has rarely been observed and described in patients with unilateral GO ever since. Drescher and Benedict [2] have made the most accurate statement in evaluating unilateral or asymmetric GO when they stated: ‘The data presented . . . are not intended to be comparable . . . , since dissimilar criteria were used . . . . in the selection of cases’. The mean prominence in their series of 200 normal eyes was 17.3 mm Hertel readings. The mean of measurements for the ‘base eye’ in all cases in their series, excluding cases of exophthalmic goitre and those of exophthalmos of unknown origin was 17.2 mm. This compares closely with the normal figure. The mean of measurements for the ‘base eye’ for the group with exophthalmic goitre, however, was 19.1 mm, thus a difference of 1.9 mm. This variation was statistically significant and exceeded 5-fold the standard deviation of the mean. Thus, they found that in cases of unilateral exophthalmic goiter the supposedly uninvolved eye that lies within the ‘normal’ range of prominence is more prominent by an average of almost 2 mm than the eye in cases of exophthalmos of any other cause. Accordingly, since exophthalmos obviously involves both orbits, it is believed preferable to use the term ‘asymmetric exophthalmos’ when discussing cases of exophthalmic goitre in which clinically ocular involvement appears to be unilateral (figs. 1–3). Hence, almost all patients with GO, even asymptomatic cases, show some degree of clinical signs with extraocular muscle involvement demonstrable by an abnormal ultrasound pattern or raised intraocular pressure in upgaze [10–17]. In our own series of 105 patients with Graves’ disease, 76 (72.3%) patients had only minor clinical signs of thyroid eye disease (NOSPECS class 2), but 100 (95.2%) had a sound evidence of GO ultrasonographically with enlarged extraocular muscles and altered ultrasound pattern of the enlarged extraocular muscles correlating with GO. Six patients (5.7%) had unilateral disease of whom 1 patient (0.9%) with monomuscular active GO (enlarged inferior rectus muscle

Fig. 1. Unilateral GO in an elderly male diabetic patient who was a heavy smoker and presented dysthyroid optic neuropathy restricted to the right eye.

Fig. 2. Asymmetric active GO.

Fig. 3. Asymmetric inactive GO.

with low reflectivity) and another patient with inactive fibrotic changes of his right inferior and medial rectus muscle (enlarged muscles with high reflectivity) were shown. All others had involvement of at least two or more extraocular muscles. Two patients were borderline in relation to thickness and reflectivity of their extraocular muscles but developed clinical signs of bilateral GO 3 and 7 months

Table 1. Characteristics of unilateral versus bilateral eye disease in 90 patients with untreated GO

1Affected eye only; 2mean of both eyes.

Values are mean SD. n.s. Non-significant. From Wiersinga et al. [28].

later respectively. Only 5 patients (4.7%) showed neither signs nor any symptoms of GO [unpubl. data]. Similar data have been generated by other investigators [18–20]. A number of patients with presumed thyroid aetiology of unilateral GO have been shown to have CT and ultrasound evidence of unilateral disease with muscle enlargement without evident abnormal thyroid studies [21]. As already mentioned in previous chapters, there is CT, MRI and/or ultrasound evidence for orbital involvement in almost all patients with autoimmune hyperthyroidism. Clinical evidence of bilateral GO occurs in 80–90% of cases. In unilateral GO clinical signs and symptoms can be found in one orbit only and true unilateral cases are present in 10–20% of patients [22–26]. Variants of different clinical presentations are often called atypical. Among patients referred to a specialized diagnostic ophthalmology unit, the percentage of unilateral cases is even higher. In one study, 11.6% of the patients had apparent unilateral disease [27] and in a study of 90 untreated patients with autoimmune thyroid eye disease referred to a single centre 14% had unilateral findings (table 1) [28]. Many patients with presumed unilateral disease have subtle signs of the other orbit such as increased IOP in upgaze or enlarged extraocular muscles on CT and/or MRI [29]. A study by Enzmann et al. [30] revealed 50% of presumed unilateral GO as having bilateral orbital disease, when evaluated by CT scan. Only 6% were confirmed to be unilateral, all other cases were found to be asymmetric. In patients with unilateral exophthalmos evaluated by ophthalmologists, the aetiology is GO in 10–30% of cases. In a recent (unpublished) retrospective observational case control series of the Orbital Center at the Academic Medical Center, Wiersinga and co-workers