Gravesova orbitopatija (GO) je autoimuna upalna bolest koja može dovesti do sekundarnog porasta intraokularnog tlaka (IOT) te gubitka ganglijskih stanica i aksona mrežnice. Bolest je rijetka, a glaukom kao komplikacija još je rjeđi i nastaje drugačijim mehanizmom od primarnog glaukoma otvorenog kuta (POAG). Cilj ovog istraživanja bio je utvrditi učestalost i narav strukturno-funkcijske (s-f) korelacije oštećenja vidnog živca i vidnog polja u bolesnika s GO-om, GO-om s povišenim IOT-om i bolesnika s POAG-om korištenjem Polar analize, alata vidnog polja Octopus 900 i optičke koherentne tomografije kao mogućnost dobivanja objektivne s-f mape koja će se moći koristiti u kliničkoj praksi. Također je istražena i uloga rizičnih čimbenika za razvoj povišenog IOT-a u bolesnika s GO-om. Rezultati ovog istraživanja pokazali su kako se kod POAG-a lokalizirani defekti vidnog polja nalaze u centralnoj i paracentralnoj regiji te u području nazalne stepenice, dok su ispadi u bolesnika s GO-om više nespecifični arkuatni i difuzni. Parametri glave vidnog živca kao što su prosječna debljina neuroretinalnog ruba, prosječni i vertikalni c/d omjeri te volumen ekskavacije papile mogu uspješnije detektirati početne promjene na glavi vidnog živca između GO i GO IOT skupine te bolje diferenciraju GO i GO IOT skupine u odnosu na prosječnu vrijednost RNFL-a. U skupini GO najjača korelacija s-f promjena pokazala se u sektoru 7, a u GO IOT-u u sektorima 1 i 7, dok je kod POAG-a, bila prisutna u 6 sektora (1,6,7, 8, 11 i 12). Povišene vrijednosti IOT-a kod GO ispitanika ukazuju na s-f oštećenja koja odgovaraju onima koja se javljaju kod ranog glaukoma. Bolesnici u skupini GO IOT su bili u prosijeku 6 godina stariji, imali su više vrijednosti IOTa, tanju rožnicu, veći c/d omjer, više vrijednosti egzoftalmometrije, nešto manji interkvartilini raspon BCVA, više stadije aktivnosti bolesti (CAS i SPECS) te su u prosjeku godinu dulje bolovali od bolesti štitnjače u odnosu na GO skupinu. Pronađeno je kako vrijednosti Anti-TG povećavaju šansu za razvoj povišenog IOT-a. Pušenje se pokazalo kao važan čimbenik rizika za pojavu GO-a, no nije nađeno da bi bilo rizični čimbenik za porast IOT-a. Primjena RAI-a primijećena je u nešto većem, ali ne značajnom postotku u skupini GO IOT. Sistemna uporaba steroida, stres i komorbiditeti nisu se pokazali kao čimbenici rizika za razvoj povišenog IOT-a
|Abstract (english)|| |
Dysthyroid orbitopathy or Graves' orbitopathy (GO) is an autoimmune inflammatory disease, which can lead to a secondary rise in intraocular pressure (IOP) and consequent loss of retinal ganglion cells and axons of the retina. It is a rare disease, and glaucoma as a complication is even rarer, arising from a different mechanism than primary open-angle glaucoma (POAG). The study aims to correlate functional visual field changes with structural changes in the optic nerve using the Polar Analysis, a tool of the Octopus 900 visual field, and optical coherence tomography. The localization and the extent of structuralfunctional changes in patients with GO, GO with raised IOP, and POAG will be compared to determine if the elevation of IOP in GO causes significant changes and if the hypotensive therapy is always necessary. The existence of possible risk factors for the development of ocular hypertension in GO patients, and the formation of an objective structural-functional map that could be used to improve the ability of clinicians to diagnose, monitor, and treat glaucoma in GO patients will be explored as well. Patients and Methods: The study included 182 subjects with GO and POAG without signs of other eye diseases that were divided into three groups. The first group consisted of 48 subjects (94 eyes) with a clinical presentation of mild to moderate GO and normal values of IOP. The second group included 50 subjects (97 eyes) with mild to moderate GO and IOP values > 21 mmHg. The third group consisted of 84 subjects (153 eyes) with POAG on antiglaucoma therapy. A complete ophthalmological examination (BCVA, IOP, CCT, exophthalmometry, gonioscopy) was performed on each subject, and the visual field was recorded using the G2 program of the Octopus 900 perimeter. Optical coherence tomography (OCT) measured the average retinal nerve fiber layer thickness (RNFL) and RNFL thickness in 12 clock - hour sectors. Global visual field parameters and OCT parameters of the optic nerve head and macula between the three examined groups were analyzed. The Octopus Polar Analysis is divided into 12 sectors corresponding to the clock-hour RNFL thickness sectors obtained by OCT. The calculated damage in dB was correlated with the structural damage on OCT in the same region, in μm. Also, for each subject with GO, the index of disease activity based on clinical signs (CAS), the severity of the disease by NOSPECS and EUGOGO classification, the concentration of thyroid hormones (fT3 and fT4), TSH and thyroid antibodies, thyroid function, duration of orbitopathy and thyroid disease and therapy of thyroid disease were analyzed. The possible existence of risk factors for the development of raised IOP in patients with GO such as smoking, stress, family history, and the presence of systemic diseases was investigated as well. Results of this study showed that in POAG localized VP defects are mainly found in the central and paracentral region and the area of the nasal step, while VP defects in patients with orbitopathy, with or without IOP are more nonspecific, arcuate, and diffuse. Furthermore, the results show that optic nerve head parameters such as average neuroretinal rim thickness, average and vertical c/d ratios, and cup volume can more successfully detect initial changes at the optic nerve head between GO and GO IOP groups and better differentiate GO and GO IOP groups relative to the average RNFL value. In the GO group, the strongest correlation of structural and functional changes was shown in sector 7, in the GO IOP in sectors 1 and 7, and in POAG, even in 6 sectors (1,6,7, 8, 11, and 12). The elevated IOP values in GO subjects can be associated with impaired structure and function, as they indicate s-f impairments corresponding to those occurring in early glaucoma. Most ocular factors for the development of glaucoma were positive in the GO IOP group, which also had a more severe clinical presentation. Patients in the GO IOP group were on average 6 years older, had higher IOP values, thinner cornea, higher c/d ratio, higher exophthalmometry values, slightly smaller interquartile range of BCVA, higher stages of disease activity (CAS and NOSPECS) and had been suffering from thyroid disease for an average of one year longer compared to the GO group. Anti-TG values were found to increase the chance of developing elevated IOP. Additionally, the results of the study show that smoking is an important risk factor for the occurrence of GO, because in the group of patients with GO and GO IOP smokers were significantly more present than in the general population. However, it cannot be argued that smoking was associated with an increase in IOP, as smokers were equally represented in the GO and GO-IOP groups. Systemic steroid use was not associated with elevated IOP in GO patients. The application of RAI was observed in a slightly higher but not significant percentage in the GO IOP group. Stress at the time of diagnosis of thyroid disease was significantly more prevalent in the GO group compared with GO IOP, confirming the observation that GO often manifests after emotional trauma, but has not been found to have an impact on IOP development. Most patients did not have other comorbidities such as diabetes, hypertension, hyperlipidaemia, depression, asthma, and COPD, so this study could not confirm the association of these disorders with the occurrence of elevated IOP in patients with GO. Conclusion: Given the finding of s-f correlations and risk factor analysis, in all patients with GO, regular measurements of IOP, an annual examination of the visual field and OCT should be performed, and in the presence of one or more risk factors, especially elevated IOP,
antiglaucoma therapy should be introduced.