Treatment Of Ophthalmopathy Research Articles

Crocin Inhibits Orbital Fibroblasts Fibrosis in Thyroid-Associated Ophthalmopathy

Purpose To investigate the role of Crocin on proliferation, fibrosis, and migration of orbital fibroblasts, as well as the possible signaling pathway. Methods Immunofluorescence assay was performed to detect the expression of fibroblast marker proteins vimentin cytokeratin, desmin, and S-100. The quantity of 5‑ethynyl‑2′‑deoxyuridine-positive cells in orbital fibroblast was analyzed. Quantitative real-time PCR and western blots were performed to evaluate the expression level of fibrosis-related marker including alpha-smooth muscle actin, connective-tissue growth factor, collagen 1A1, and fibronectin. Scratch wound assays were performed to assess wound widths of orbital fibroblast. The expression and phosphorylation of extracellular signal-regulated kinase/signal transducer and activator of transcription 3 were evaluated using western blots. The phosphorylation of smad2 and smad3 was evaluated using immunofluorescence assay. Results Crocin treatment reduced 5‑ethynyl‑2′‑deoxyuridine-positive cells, indicating inhibitory effect on orbital fibroblast proliferation. The expression levels of alpha-smooth muscle actin, connective-tissue growth factor, collagen 1A1 and fibronectin were declined in Crocin treatment. Delayed wound closures were observed in Crocin treatment. Furthermore, Crocin did not affect the expression of extracellular signal-regulated kinase and signal transducer and activator of transcription 3, but weakened extracellular signal-regulated kinase and signal transducer and activator of transcription 3 phosphorylation in orbital fibroblast. The phosphorylation of smad2 and smad3 was attenuated by Crocin as well. Conclusion In conclusion, Crocin inhibits the phosphorylation of extracellular signal-regulated kinase and signal transducer and activator of transcription 3, contributing to the inhibitory effect on proliferation, fibrosis, and migration of orbital fibroblast, suggesting that Crocin has potential to be a novel therapeutic candidate for thyroid-associated ophthalmopathy treatment.

Nanotechnology Lighting the Way for Gene Therapy in Ophthalmopathy: From Opportunities toward Applications.

Hereditary ophthalmopathy is a well-described threat to human visual health affecting millions of people. Gene therapy for ophthalmopathy has received widespread attention with the increasing understanding of pathogenic genes. Effective and safe delivery of accurate nucleic acid drugs (NADs) is the core of gene therapy. Efficient nanodelivery and nanomodification technologies, appropriate targeted genes, and the choice of drug injection methods are the guiding lights of gene therapy. Compared with traditional drugs, NADs can specifically change the expression of specific genes or restore the normal function of mutant genes. Nanodelivery carriers can improve targeting and nanomodification can improve the stability of NADs. Therefore, NADs, which can fundamentally solve pathogeny, hold great promise in the treatment of ophthalmopathy. This paper reviews the limitations of ocular disease treatment, discusses the classification of NADs in ophthalmology, reveals the delivery strategies of NADs to improve bioavailability, targeting, and stability, and summarizes the mechanisms of NADs in ophthalmopathy.

GAO Wei-bin's clinical experience of electric eye acupuncture and stagnant-moving needling for ophthalmopathy

Professor GAO Wei-bin's clinical experience of electric eye acupuncture and stagnant-moving needling for ophthalmopathy was introduced. The indications of electric eye acupuncture and stagnant-moving needling include external ophtalmoplegia and visual impairment. Professor GAO has proposed new acupoints at the ocular muscles attachment of eyeball, and put forward five experience points: Shangming point, Neiming point, Xiaming point, Waiming point and Tijian point. The points are selected according to different pathological changes of ocular muscles. In the treatment of ophthalmopathy, the tendons and vessels are often regulated at the same time. Neiming point, Shangming point, Xiaming point and Qiuhou point are the main points, with Fengchi (GB 20) and Gongxue (Extra) as the matching points. In addition, attention is paid to the application of stagnant-moving needling and electroacupuncture (continuous dense wave, frequency of 50 Hz).

Опыт лечения эндокринной офтальмопатии

Опыт лечения эндокринной офтальмопатии

Clinical Features of Graves' Ophthalmopathy and Impact of Enalapril on the Course of Mild Graves' Ophthalmopathy: A Pilot Study.

Inflammation, oxidative stress, and adipogenesis are associated with Graves' ophthalmopathy (GO) progression. We conducted a pilot study to investigate the effect of Enalapril on patients with mild ophthalmopathy. Based on the comprehensive eye examination, 12 patients with mild ophthalmopathy were selected from referred Graves' patients and treated with Enalapril (5 mg daily) for 6 months. Clinical and ophthalmological examination [IOP (Intraocular Pressure), vision, Margin reflex distance and exophthalmia measurement, CAS (clinical activity score) and VISA [V (vision); I (inflammation/ congestion); S (strabismus/motility restriction); and A (appearance/exposure] score assessment) was performed at the beginning, 3 months and 6 months of the study period. Quality of life was also evaluated using a standard questionnaire. Mean exophthalmia at the first visit was 18.75 ± 2.39, 3 months later 18.53 ± 2.39 and 6 months later was 17.92 ± 2.31, respectively. Mean CAS was 0.71 ± 0.82 (first visit), 0.57 ± 0.54 (3 months) and 0.14 ± 0.36 (6 months), respectively. Mean Margin reflex distance was 9.09 ± 4.36 (first visit) and 9.60 ± 4.40 (6 months), respectively. There were significant differences in the case of exophthalmia (P=0.002), CAS (P=0.006), and Margin reflex distance (P=0.029) between the first visit and 6 months after treatment. The difference between the score of quality of life in patients with GO after 6 months of follow up was statistically significant (P = 0.006). Our results showed that Enalapril treatment could ameliorate the clinical course of GO according to the ophthalmologic examinations and subjective parameters of disease progression. However, further studies should be performed to determine the efficacy of Enalapril in Graves' ophthalmopathy treatment.

Treatment of ophthalmopathy in the course of Graves' disease

Treatment of ophthalmopathy in the course of Graves' disease

Immunogammopathy maculopathy

Immunogammopathy maculopathy is a newly discovered retinopathy associated with macroglobulinemia in recent years. The main manifestations were retinal vein convulsion and dilation caused by high blood viscosity, retinal interlaminar effusion and macular serous detachment. With the prolongation of the course of disease, the photoreceptor layer and RPE layer in the detachment area showed atrophic changes. The pathogenesis of ophthalmopathy is still unknown. Understanding the clinical features, diagnosis, differential diagnosis and treatment of ophthalmopathy is of great significance for understanding this kind of disease and improving the level of diagnosis and treatment of ophthalmopathy. Key words: Immunoglobulins; Macular degenerat; Waldenstrom macroglobulinemia; Review

P.2.e.006 - Antidepressant-like properties of the GPR39 (zinc receptor) agonist

To present results of irradiation of ophthalmopathy in the course of Graves-Basedow disease performed in the Radiotherapy Laboratory in University Children's Hospital in Cracow by staff of the Oncology Clinic, Collegium Medicum Jagiellonian University (CM UJ).During the period of 2000–2003 therapeutic irradiation of the retrobulbar area was performed in 121 patients with malignant exophthalmos using a total dose of 20 Gy/ 10 fractions of 6 MV photonic beam in the Radiotherapy Laboratory in University Children's Hospital in Cracow. Execution of the treatment plan was controlled by in vivo dose measurements using semiconducting detectors, MOSFET type. Radiotherapy was preceded by intravenous corticosteroid therapy (Solu Medrol) with a dose of 2g/ week for 4 weeks.During the irradiation treatment 9 patients (7.4%) developed an acute post-radiation reaction of transient character. Ophthalmological control examination revealed an improvement in 97 patients (80.2%) in the form of reduction or total regression of ophthalmopathy symptoms; in 21 other patients (17.3%) stabilization was noted and progression in 3 (2.5%).Radiotherapy is a well-tolerated method of ophthalmopathy treatment in the cour se of Graves-Basedow disease. Efficacy of radiotherapy as an exclusive method of malignant exophthalmos treatment seems to be lower in comparison to irradiation combined with corticosteroid therapy.

The role of thyrotropin receptor antibodies in Grave’s Ophthalmopathy treatment

Background. Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder affecting the retroorbital tissues. Although the role of TRAb in GO is now accepted by many researchers and clinicians, their use in the disease management of GO is less well studied than the role of TRAb for the diagnosis and therapy monitoring of Graves’ disease.Aim: to evaluate the relation between TRAb level and the activity of GO, the course of GO and the effectiveness of the treatment.Materials and methods. We have studied 26 patients with GO and Grave’s Disease. Activity of GO was measured with the clinical activity score (CAS), we defined active GO as a CAS≥3. TSH, FT4 and TRAb were evaluated. All patients had received intravenous methylprednisolone (ivMP) pulse therapy in cumulative dose 6000 mg. We observed patients for 1 year after pulse therapy. TRAb level was evaluated before, 3, 6 and 12 months after pulse therapy.Results: At the time of initial treatment all patients had active GO, 60% with CAS 3-4 and 40% with CAS 5-7. On year after the pulse therapy of GO, all patients were classified into responders (69,2%) and non-responders (30,8%) according to their clinical manifestations. Pulse therapy considered as effective if GO activity decreased with CAS ≤ 2. Serum TRAb level was significantly higher in patients who non-responded to therapy – 34,8 U/L vs 17,5 U/L (p≤0,01). This level was significantly decreased in patients responded to treatment – 1,6 U/L vs 12,4 U/L (p≤0,01). TRAb level above 28,8 U/L before treatment (p≤0,01), 10,1 U/L after 3 months of treatment (p≤0,01), 5,1 U/L after 6 months of treatment (p≤0,01) and 8,2 U/L after 3 months of treatment (p≤0.01) was associated with higher risk of non-responding.Conclusion: We conclude, that TRAb level may serve not only as predictor of GO activity and severity, but changes in the level of antibodies could be of additional help for the disease management with ivMP.

Steroid-induced thyrotoxic periodic paralysis during Graves' ophthalmopathy treatment

Graves' ophthalmopathy (GO) is the most common extrathyroidal manifestation of Graves' disease (GD). Severe ophthalmopathy is identified in 3–5% of patients with GD.1 GO is usually present bilaterally, affecting patients...

Volumetric Modulated Arc Therapy (VMAT) make a difference in retro-orbital irradiation treatment of patients with bilateral Graves’ ophthalmopathy. Comparative analysis of dosimetric parameters from different radiation techniques

BackgroundGraves’ ophthalmopathy is the commonest extrathyroidal manifestation of Graves’ disease. Treatment options include steroid therapy, corrective/decompressive surgery, radiation therapy or combination of these approaches. AimOur purpose was to investigate if retro-orbital irradiation with Volumetric Modulated Arc Therapy (VMAT) yielded better target coverage and dose sparing to adjacent normal structures compared to 3-Dimensional Conformal Radiotherapy (3DCRT) and Lateral Opposing Conformed Fields (LOCF). MethodsFourteen consecutive patients diagnosed with bilateral Graves’ ophthalmopathy were prospectively recruited into this study from August 2012 until August 2014. An individual VMAT, 3DCRT and LOF plan was created for each patient. Conformity Index (CI), Homogeneity Index (HI) and other dosimetric parameters of the targets and organs-at-risk (OAR) were analyzed in all 28 orbits compared between the different techniques. ResultsCI generated by VMAT was superior to that produced by 3DCRT(p<.001) and LOF (p<.001). As expected, 3DCRT was also superior to LOF (p=.007). Regarding the OARs sparing dose (lens, globes, retina and lacrimal glands), VMAT showed a significant benefit when compared with 3DCRT and LOCF, with no differences between the two latter techniques. ConclusionsVMAT should be preferred over 3DCRT and LOF for bilateral Graves’ ophthalmopathy treatment.

Efficacy of Puls-therapy with Glucocorticoids in Patients with Autoimmune Ophtalmopatay

The article is presents the results of estimation efficiency of various schemes pathogenetic glucocorticoids treatment of autoimmune ophthalmopathy. Research of clinical parameters dynamics including subjective and objective attributes, proptosis, dynamics of the soluble form of intercellular molecule adhesion-1 levels was made before treatment and at the end of research (in 6 month follow up after complete course of pathogenetic treatment). The study has demonstrated that combination of glucocorticoids pulse-therapy and mean volume plasmapheresis is the most effective pathogenetic method of autoimmune ophthalmopathy treatment; absence of advantages of the used schemes of treatment for reduction proptosis. Advantages of use of the combined therapy are marked in comparison with monotherapy by glucocorticoids at estimation of subjective attributes.

O.348 Piezoelectric surgery in Graves' ophthalmopathy treatment

O.348 Piezoelectric surgery in Graves' ophthalmopathy treatment

Irradiation of malignant exophthalmos in the course of Graves Basedow disease

Summary Aim To present results of irradiation of ophthalmopathy in the course of Graves-Basedow disease performed in the Radiotherapy Laboratory in University Children's Hospital in Cracow by staff of the Oncology Clinic, Collegium Medicum Jagiellonian University (CM UJ). Material and Method During the period of 2000–2003 therapeutic irradiation of the retrobulbar area was performed in 121 patients with malignant exophthalmos using a total dose of 20 Gy/ 10 fractions of 6 MV photonic beam in the Radiotherapy Laboratory in University Children's Hospital in Cracow. Execution of the treatment plan was controlled by in vivo dose measurements using semiconducting detectors, MOSFET type. Radiotherapy was preceded by intravenous corticosteroid therapy (Solu Medrol) with a dose of 2g/ week for 4 weeks. Results During the irradiation treatment 9 patients (7.4%) developed an acute post-radiation reaction of transient character. Ophthalmological control examination revealed an improvement in 97 patients (80.2%) in the form of reduction or total regression of ophthalmopathy symptoms; in 21 other patients (17.3%) stabilization was noted and progression in 3 (2.5%). Conclusions Radiotherapy is a well-tolerated method of ophthalmopathy treatment in the cour se of Graves-Basedow disease. Efficacy of radiotherapy as an exclusive method of malignant exophthalmos treatment seems to be lower in comparison to irradiation combined with corticosteroid therapy.

Peripheral parameters of oxidative stress in patients with infiltrative Graves’ ophthalmopathy treated with corticosteroids

Infiltrative ophthalmopathy, which may develop in patients with Graves’ disease, is considered an inflammatory disorder of autoimmune background. There is growing evidence that changed reactive oxygen species (ROS) metabolism plays an important role in pathogenesis of autoimmune diseases. Corticotherapy is a principal method of ophthalmopathy treatment, and its therapeutic effect is partially connected with influence on ROS generation systems. This study was undertaken to investigate corticosteroids treatment influence on blood extracellular indices of ROS metabolism in Graves’ ophthalmopathy patients. Plasma indices of free radical generation and scavenging were determined in 22 euthyroid patients with active infiltrative Graves’ ophthalmopathy initially, after intensive corticotherapy and after completing of steroid treatment. Age- and sex-matched 24 healthy volunteers and 25 euthyroid Graves’ patients without overt ophthalmopathy served as controls. In the ophthalmopathy patients hydrogen peroxide (H 2O 2), lipid hydroperoxides (ROOH), thiobarbituric acid-reacting substances (TBARS) and ceruloplasmin (CP) levels and superoxide dismutase (SOD) and catalase (CAT) activities were increased, whereas glutathione peroxidase (GPx) and glutathione reductase (GR) activities were reduced. Intensive corticotherapy resulted in normalization (partial for ROOH) of ROS metabolism peripheral markers. After the withdrawal of corticosteroids a reduction of ophthalmopathy clinical activity was present, yet a marked restoration of increased oxidative stress indices was observed, along with activation of antioxidant defence systems (not significant for CAT activity). These data demonstrate that corticosteroids are effective in reduction of peripheral oxidative stress present in infiltrative Graves’ ophthalmopathy, but this effect tends to be transient.

Management of thyroid ophthalmopathy.

The pathogenesis of thyroid ophthalmopathy and its relation to thyroid gland dysfunction defies elucidation, and thus only palliative therapy exists. If and how antithyroid therapy affects the course of thyroid eye disease remains controversial. Research continues to try to reveal a subset of patients who respond best to corticosteroid or radiation treatment. Innovations in the surgical correction of upper eyelid retraction, orbital decompression technique, and the approach to restrictive myopathy help improve outcome. Preliminary knowledge concerning octreotide suggests that it may play a role in thyroid ophthalmopathy treatment and prevention. Future studies still need to answer basic questions about the treatment of thyroid ophthalmopathy.

The value of visual evoked potentials in optic neuropathy of Graves' disease.

Visual evoked potentials (VEP) were tested in patients with ophthalmopathy (OP) of Graves' disease (GD) before treatment and half-a-year and 5-7 yr after orbital decompression (7 patients) or retrobulbar irradiation (3 patients). Five patients not requiring treatment for OP and 16 healthy subjects served as controls. Treatment of OP was given on clinical grounds including decreased visual acuity (VA) indicating optic neuropathy. Before treatment VA was decreased in 5 out of 19 eyes whereas VEP were abnormal in all. The mean latency at N60 both in the operated (83.1 +/- 21.6 ms) and in the irradiated groups (80.9 +/- 7.0 ms) was significantly different from that in the untreated group (62.6 +/- 8.2 ms; p < 0.001) and the healthy subjects (58.9 +/- 6.3; p < 0.001). At P120 only the latency of the operated group differed significantly from that of the other groups (p < 0.001). There was a relationship between the eye muscle changes seen on CT scans and the ophthalmopathy score (according to the classification of the American Thyroid Association) and the latency both at N60 and P120. A change from a V-shape to a W-shape of the waves occurred more often in the treated patients before therapy than in the other groups. Two patients had multiphase VEP in both eyes which improved after treatment. After adequate clinical response the visual acuity improved in one of the 5 patients with initially depressed VA. VEP, initially abnormal in all, improved in 7 of the 19 eyes (37%) but further deterioration was observed in 8 (42%).(ABSTRACT TRUNCATED AT 250 WORDS)

Choice of Therapy and Criteria for Assessing Treatment Outcome in Thyroid-associated Ophthalmopathy

Treatment recommended for thyroid-associated ophthalmopathy varies with the particular expression of the disease in a given patient. Medical therapy may be beneficial in the early phase before extensive fibrosis of retro-ocular muscles and connective tissue is established. Although corticosteroids reliably suppress acute inflammatory changes, evidence supporting efficacy of plasmapheresis, immunosuppressive drugs, iodine-131 ablation, and radiotherapy is inconclusive. Surgery on eyelids, extraocular muscles, and orbit effectively rehabilitates most patients with even the most severe ophthalmopathy while having no effect on the underlying autoimmune process. Future research should include continued attempts to identify the putative target antigens in the orbit and to define the controls of glycosaminoglycan synthesis. Until prevention by immunologic or other medical means is attainable, surgery on orbit, muscles, and eyelids appears the most effective mode of treatment for correction of the functional and cosmetic consequences of the ophthalmopathy associated with autoimmune thyroid disease.

Attempt at thyroid ablation with radioactive iodine for the treatment of ophthalmopathy in Graves' disease.

Attempt at thyroid ablation with radioactive iodine for the treatment of ophthalmopathy in Graves' disease.