Assessment of Clinical Signs, Retinal Nerve Fiber Layer and Central Macular Thickness in Patients with Graves Ophthalmopathy

Jurate Jankauskiene^1*, Dalia Jarushaitiene¹

¹Eye Clinic of Lithuanian University of Health Sciences, Mickevichiaus 9, Kaunas, LT-44307, Lithuania

*Correspondence author: Jurate Jankauskiene, MD, Clinic of Eye Diseases, Lithuanian University of Health Sciences, Mickevichiaus 9, Kaunas, LT-44307, Lithuania; Email: jurate.jankauskiene@lsmu.lt

Citation: Jankauskiene J, et al. Assessment of Clinical Signs, Retinal Nerve Fiber Layer and Central Macular Thickness in Patients with Graves Ophthalmopathy. J Ophthalmol Adv Res. 2025;6(2):1-8.

Copyright^© 2025 by Jankauskiene J, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Table 1: CAS, BCVA, IOP, exophthalmos values and OCT parameters.

Exophthalmos results ranged from 13.9 to 23.3 mm. The mean was 18.26 ± 2.07mm. The mean of RNFL thickness was 96.84± 11.27μm and Central macular thickness was 271.43 ± 22.82μm. A statistically significant correlation was found between BCVA and RNFL, CMT thickness (r=0.376, p=0.001, r=0.258, p=0.026, respectively). A negative significant relationship was between CAS and RNFL, CMT (r=-0.406, p<0.001; r=-0.233, p=0.046, respectively). These data indicate that the lower the visual acuity and the higher the disease activity, the smaller the RNFL and the CMT.

Table 2: Correlation between RNFL, CMT and CAS, BCVA, IOP, exophthalmos values.

A negative significant association was between IOP, exophthalmos and RNFL (r=-0.348, p=0.002; r=-0.287, p=0.013, respectively). The changes indicate that the greater IOP and exophthalmos the thinner RNFL. However, there were no statistically significant correlations between IOP, exophthalmos and CMT (r=-0.14, p=0.235; r=-0.2, p=0.088, respectively).

Discussion

GO is an autoimmune disease and occurs in most cases in patients with Graves’ disease [3,25]. Clinical data for GO vary depending on the location of the affected orbital soft tissue. Approximately 40% GO patients experience extraocular muscles edema. It usually occurs in the elderly, leading to more severe symptoms, including edema of the conjunctiva and eyelids, restriction of eye movement, compression of the optic nerve [26,27].

A study by Eslami, et al., showed that intraocular hypertension was found in men with longterm GO, smokers and patients who had been treated for thyroid disease for a long time [28]. It has been found that patients with active GO often complain of deteriorating vision, since a correlation has been established between the clinical activity 15 of the disease and visual acuity. The results of the authors’ studies showed that visual acuity 6 in Graves‘Ophthalmopathy patients correlated statistically significantly with disease activity. During the study, the decrease in disease activity may indicate an improvement in the condition of the eye or the effectiveness of treatment, therefore vision improvement  may be related to a decrease in inflammation of the orbital tissue and extraocular muscles [29].

There is little scientific literature examining OCT data and the relationship between exophthalmos, Graves’ Ophthalmopathy activity and CMT and RNFL. We can compare the results of our research with the data obtained from the global scientific literature. Studies have shown that there is no relationship between RNFL thickness and other GO parameters, either positive or negative correlations.

Wei, et al., studied GO patients who had limited eye movement. They reported that changes in extraocular muscle obtained by computed tomography were not significantly associated with either VA or proptosis or RNFL. According to this sudy visual acuity was not significantly correlated with RNFL thickness [30]. According to some authors, the decrease in the thickness of fiber layer 2 was associated with decreased density of capillars in the peripapillary area [31].

Akpolat, et al., noted that there was no statistically significant difference in central retinal thickness between inactive GO and healthy persons and there was no correlation between central retinal thickness and other parameters in patients with Graves ophthalmopathy. However, a positive correlation was found between the vascular density of the parafoveal segments of these patients. The authors think that optical coherent tomography angiography could be a new and promising non-invasive diagnostic technique for patients with inactive Graves ophthalmopathy to detect changes in foveal and parafoveal vascular density [32].

K Mugdha, et al., showed tha the average RNFL thickness in GO was significantly lower than that of the controls. No relationship was between changes in CAS and RNFL thickness. Assessment of RNFL is very important in Graves’ Disease and in cases of severe damage, active intervention may be required [33].

Sayın, et al., assessed that Intraocular pressure and exophthalmos were greater in Graves‘ ophthalmopathy patients. The authors showed no significant difference in RNFL between patients with GO and healthy control patients., while macular and inferior RNFL thickness was lower compared to healthy controls [34]. Sen, et al., reported that intraocular pressure was greater in GO, the mean thickness of RNFL in GO patients was smaller than in the control group. 3 The authors assume that prolonged hypoxia and ischaemia were associated with optic nerve atrophy and desrease in thickness of RNFL [35]. Meirovitch, et al., indicated that OCT data in patients with GO detect retinal and optic nerve changes earlier and allow for earlier diagnosis and timely treatment to avoid severe visual consequences [36]. Iorga, et al., indicate that OCT is useful for compressive optic neuropathy diagnosis and monitoring treatment by observing the condition of the optic nerve [37]. Park, et al., revealed a reduction 8 in temporal peripapillary RNFL thickness in eyes with chronic optic neuropathy of GO patients compared to eyes with acute optic neuropathy. They found a significant association between inferior peripapillary RNFL thickness and visual acuity. Thicker inferior peripapillary thickness of RNFL was associated with better visual outcomes [38].

Our study found significant relationship between best visual acuity and RNFL thickness and central macular thickness. These data suggest that the lower the visual acuity, the smaller the RNFL and thickness of central macula.

The study of Akkus, et al., assessed significant negative relationship of RNFL measurements with serum TRAb, antiTPO, fT3, fT4 (p<0.05). The authors think that baseline serum levels of fT3, fT4 and TRAb in patients with Graves’ disease may be a prognostic factor in assessing the nerve fibre layer in patients with GO [39].

In patients with Graves Ophthalmopathy, G Casini, et al., found 2 lower central macular and ganglion cell layer thickness. The authors summarise that these morphology changes indicate the possible influence of the orbital inflammatory process [40]. Furthermore, our study shows significant negative relationship between Clinical activity score and RNFL, as well as CMT. These changes suggest that the higher the disease activity, the thinner the RNFL and CMT.

Based on the results of a study by BE Ogmen, et al., the authors compared the thickness of the retinal layer in patients with Graves‘ ophthalmopathy using spectral optical coherent tomography method. The ganglion cell layer and the inner plexiform layer in GO were thinner than in healthy individuals [41].

Joo, et al., describe OCT data in various optic neuropathies and showed a decrease in RNFL in this pathology. The authors argue that the correlation between the best-corrected visual acuity and internal retina thickness, based on the findings of OCT parameters, helps to assess the aetiology of optic neuropathy [42].

We found a negative significant  relationshipr between IOP, exophthalmos and RNFL. The data suggest that the greater IOP and exophthalmos the thinner RNFL. In our study we did not find significant relationship between IOP, exophthalmos and central macular thickness. Some other studies have reported different approaches to RNFL thickness.

Dave, et al., showed that patients with active form of Graves‘ ophthalmopathy had lower peripapillary and macular vascular indexes. They also found that RNFL was greater in patients with active form of Graves‘ ophthalmopathy. In case of inactivity of the disease, these parameters were similar to those of healthy eyes [43].

Cheng, et al., indicated that after orbital decompression surgery, improvement in BCVA, a decrease in RNFL thickness in all patients with GO and optic neuropathy except the nasal quadrant was established [5,26]. Nasal RNFL thickness was an good predictor of postoperative improvement in BCVA. RNFL as measured in OCT correlated with recovery of visual function after decompression surgery in patients with optic neuropathy in GO patients, which may also be a predictor of better vaision prognosis [44].

Ioana, et al., reviewing the literature and scientific studies on retinal changes in Graves’ ophthalmopathy, found that the thickness of the TNSS varies depending on the stage and severity of GO. The thickness of RNFL in GO patients did not change statistically significantly in the moderate to low activity stages, but tended to thicken due to optic nerve oedema with the development of dysthyroid optic neuropathy. Subfoveal choroid thickness was greater in active form of GO, it correlated positively with clinical activity score and proptosis, suggesting that it may confirm the disease activity [45].

Some studies have reported that the reduction in RNFL in active GO is related to ischemia caused by orbital soft tissue edema, leading to optic nerve atrophy [35,46-48]. Chu, et al., found that plasma ET-1 levels were higher than normal in patients with thyroid hormone disorders caused by Graves’ disease. ET-1, a potent vasoconstrictor, can reduce optic nerve head blood flow. The peripapillary RNFL may be affected by ischemic conditions caused by the vasoconstrictor ET-1 [49,50].

The authors of the study suggested CMT may be useful in the early stages of glaucoma and to monitor disease progression [51].

Poostchi, et al., noted that patients without glaucoma with increased IOP resulted in increased disc area [4,52]. Vascular insufficiency in the peripapillary area, even in the absence of glaucoma, can cause damage to the optic nerve and central macula [53].

A multi-clinic study showed that Graves’ ophthalmopathy may progress with increasing TRAb titers and this may have predictive value for activity and development of the disease [54]. Kuebler, et al., describe a positive prognosis for GO patients who have experienced optic nerve compression after treatment [55].

Conclusion

In conclusion, our study shows that in patients with Graves’ ophthalmopathy, RNFL thickness was significantly correlated with disease activity, visual acuity, intraocular pressure and exophthalmos. CAS and BCVA were significantly associated with CMT. Measuring RNFL thickness may help detect optic nerve damage in GO and prevent the progression of neuropathy. These objective changes of optic nerve and retina require timely and effective treatment by an endocrinologist and an ophthalmologist.

Our study has several limitations. It was a retrospective study, which does not allow for control of dynamic OCT and clinical parameters in patients with Graves‘ ophthalmopathy. Furthermore, the number of patients was relatively small, although our results reached a statistically significant level.

Conflict of Interest

The authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding Details

There is no funding to report for this paper.

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