Dr.Saket Agrawal, Dr.ram kishore shandilya,Dr.ANIMESH SAHU,Dr.Narendra Patidar
Introduction
Graves’ disease also called thyroid associated orbitopathy (TAO) or Graves’ orbitopathy (GO) is an autoimmune condition in which autoantibodies target the thyroid-stimulating hormone receptor (TSH-R) on thyrocytes, resulting in production of excess thyroid hormone. [1] Eye disease may be associated with hyperthyroidism[2] , hypothyroidism[3] or may also be seen in euthyroid Graves’ disease. [2]
Dysthyroid Optic neuropathy is a rare complication of TED resulting from pressure on the optic nerve due to orbital swelling. It is seen only in severe cases when there is orbital compression due to enlarged extraocular muscles. [4]
Optic disc dysfunction may be present in TED patients without obvious optic neuropathy and extraocular muscle swelling. [5] Traditionally some tests such as colour vision charts, visual fields have been used to asses optic disc function in patients with TED.
Spectral domain-optical coherence tomography (SD-OCT) is a non invasive and rapid test to asses optic disc function. Few studies have reported reduction in RNFL thickness in TED patients. Plausible mechanism for the same is compressive optic neuropathy.
However, up to what extent does the damage occur in relation to clinical activity of the disease, has not been established.
We conducted this study to compare peripapillary RNFL thickness in patients with TED and healthy controls and its correlation with disease activity.
Materials and methods
This was a cross sectional, observational study conducted at oculoplasty and orbit services, Sadguru Netra Chikitsalaya, Chitrakoot between September 2017 to February 2018.
All consecutive patients who were diagnosed with TED were included. Age and gender matched healthy volunteers served as controls. Patients with hazy media where OCT is not possible, viz. dense cataracts, corneal opacities, and patients with pre existing retinal pathologies were excluded. All patients underwent a full ophthalmologic examination. Clinical activity score was used to assess activity of TED. SD-OCT was performed in all patients. Following parameters were noted:
- Mean RNFL
- Inferior RNFL
- Nasal RNFL
- Superior RNFL
- Temporal RNFL
Control group also underwent ophthalmic examination and OCT for RNFL thickness. Data was analyzed using SPSS v24. Independent ‘t’ test was used. Correlation was analyzed using pearson correlation coefficient. A value of p<0.05 was taken as statistically significant.
Results
During the study period 44 eyes of 24 cases and 46 eyes of 24 controls were evaluated. Mean age of cases was 41.42 + 15.14 years, while mean age of control group was 14.83 + 14.00 years. (p=0.922).
Mean RNFL thickness among cases was 97.6 + 9.7 µm while that in control group was 108 + 7.5 µm (p<0.001). There was significant thinning of RNFL in all quadrants in patients with TED as compared to control group. (Table 1)
Table 1: Mean RNFL results (µm)
| Study (n=44) | Control (n=46) | p value | |
| Superior quadrant | 126.7 + 18.1 | 144.4 + 18.8 | <0.001* |
| Inferior quadrant | 118.9 + 21.0 | 130.0 + 14.1 | 0.004* |
| Temporal quadrant | 69.5 + 13.2 | 77.0 + 8.6 | 0.002* |
| Nasal qudrant | 74.1 + 12.3 | 80.6 + 10.2 | 0.007* |
RNFL = retinal nerve fibre layer *p<0.05
Mean CAS was 2.75 + 1.3. RNFL thickness reduced with increase in disease activity as assessed by Clinical Activity Score (r = -0.393).
Discussion
In our study there was significant thinning of peripapillary RNFL in all quadrants. OCT was used to assess retinal function much before signs and symptoms of retinal damage set in cases of Thyroid eye disease.
There are various mechanisms which can result in thinning of RNFL. Studies have shown that there is thinning of RNFL in cases of compressive optic neuropathy. [6,7] So the results seen in our study may be due to compressive effects of TED.
Meirovitch[8] et al reported a thickening of RNFL and inner macula thinning compared to healthy subjects. The proposed mechanism for this result is inflammation associated with TED. The difference between this and our study may be attributed to the fact that mechanical compression and inflammation may coexist.
Chu et al.[9] have reported that the plasma ET-1 levels are higher than normal levels in TED. ET-1 is a strong vasoconstrictor, can cause reduced blood flow to optic nerve head. Peripapillary RNFL may be influenced by ischemia caused by the vasoconstrictor effect of ET-1 and cause it’s thinning.
Forte et al.10 found that there is a reduction in RNFL thickness in patients with TED and ocular hypertension when compared with the control group and this decrease is significantly higher in inferior and superior quadrants. In our study, a significant thinning was found in inferior RNFL thickness in TAO patients in all quadrants when compared with healthy controls.
In our study the RNFL thickness was also correlated to disease activity as assessed by clinical activity score. Higher disease activity had reduced RNFL thickness.
Conclusion
There is a thinning of RNFL in patients with TED and it is correlated to disease activity. OCT is a readily available tool to assess retinal changes. It could be used to objectively document and prognosticate the changes in RNFL in patients with TED.
References
- Prabhakar BS, Bahn RS, Smith TJ. Current perspective on the pathogenesis of Graves’ disease and ophthalmopathy. Endocr Rev 2003;24:802-3
- Marcocci C., Bartalena L., Bogazzi F., Panicucci M., Pinchera A. Studies on the occurrence of ophthalmopathy in Graves’ disease. Acta Endocrinologica. 1989;120(4):473–478
- Gleeson H, Kelly W, Toft A, Dickinson J, Kendall-Taylor P, Fleck B, et al. Severe thyroid eye disease associated with primary hypothyroidism and thyroid-associated dermopathy. Thyroid 1999;9:1115-8.
- Wiersinga WM, Kahaly GJ. Graves orbitopathy: A multidisciplinary approach. Basel: Karger; 2007
- Beden Ü, Kaya S, Yeter V, Erkan D. Contrast sensitivity of thyroid associated ophthalmopathy patients without obvious optic neuropathy. Scientific World J. 2013;2013: 943789.
- Mendoza-Santiesteban CE, Gonzalez-Garcia A, Hedges TR 3rd, et al. Optical coherence tomography for neuro-ophthalmologic diagnoses. Semin Ophthalmol 2010; 25: 144-54.
- Pasol J. Neuro-ophthalmic disease and optical coherence tomography: glaucoma look-alikes. Curr Opin Ophthalmol 2011; 22: 124-32.
- Blum Meirovitch S, Leibovitch I, Kesler A, Varssano D, Rosenblatt A, Neuderfer M. Retina and Nerve Fiber Layer Thickness in Eyes with Thyroid-Associated Ophthalmopathy. Isr Med Assoc J. 2017;19(5):277-281.
- Chu C. H., Lee J. K., Keng H. M., et al. Hyperthyroidism is associated with higher plasma endothelin-1 concentrations. Experimental Biology and Medicine. 2006;231(6):1040–1043.
- Forte R, Bonavolonta P, Vassallo P. Evaluation of retinal nerve fiber layer with optic nerve tracking optical coherence tomography in thyroid-associated Ophthalmologica 2010; 224: 116-21.
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