Volume 42 ·  Issue 12 ·  2006

The volume and cell number of orbital adipose tissue in patients with thyroid-related ophthalmopathy (TAO) increase, which not only directly leads to the increase of orbital pressure, exophthalmos and visual impairment, but also adipose tissue itself, as a new endocrine organ, can secrete a variety of adipocytokines, growth factors and protein molecules, some of which participate in the occurrence and development of TAO. Therefore, we should attach great importance to the important role of orbital adipose tissue in TAO and carry out relevant research.

Thyroid-related ophthalmopathy is the most common clinical disease with unilateral or bilateral exophthalmos. The diagnosis is not difficult, but there is no unified treatment. The key problem of treatment lies in how to correctly grasp the clinical characteristics of thyroid-related ophthalmopathy and choose the appropriate treatment method according to the clinical characteristics.

Objective to investigate the curative effect and effect characteristics of botulinum toxin A (BTXA) in the treatment of restrictive strabismus in thyroid-related ophthalmopathy (TAO). Methods the clinical data of BTXA injection in extraocular muscle in the treatment of restrictive strabismus in TAO were analyzed retrospectively. Under the guidance of electromyography, BTXA was injected into the extraocular muscle of 33 patients with restrictive strabismus in TAO. Eye position, eye movement and diplopia were recorded before and after injection. Results 25 patients had vertical strabismus, 3 cases had horizontal strabismus, and 5 cases had horizontal strabismus combined with vertical strabismus △ ±20.53 △ (20 △ ～80 △ , M =27.5 △ ), vertical strabismus 29.33 △ ±17.27 △ (10 △ ～100 △ , M =27.5 △ 61 extraocular muscles were injected, including 31 inferior rectus muscle, 16 medial rectus muscle, 10 superior rectus muscle and 4 lateral rectus muscle. The average number of injections for each extraocular muscle was (6.48±2.12) times, (4~11 times, M =6 times). The interval between injections was 0.50~26.00 months, with an average of (2.96±0.70) months. The strabismus decreased after injection, 15 cases were cured, 12 cases were effective, and 6 cases were ineffective. The average dose of single injection was (8.16±1.43) U. Conclusion BTXA is effective in the treatment of restrictive strabismus caused by TAO. The timing of injection is better in the early stage of TAO. The dose of BTXA per injection is greater than that of paralytic strabismus and common strabismus, the corrected strabismus is lower, the interval of injection and the duration of curative effect are shorter, and the injection dose needs to be increased continuously with the increase of the number of treatments. Some patients may be exempt from diplopia without surgery.

Objective to study the clinical value of 99Tcm-octreotide orbital imaging in judging the activity of ocular inflammatory response in patients with thyroid-related ophthalmopathy (TAO). Methods According to the clinical activity score (CAS) standard, 30 patients with TAO were divided into active group and inactive group, and 11 normal volunteers were the control group. All subjects underwent 99Tcm-octreotide orbital tomography, and the orbital octreotide uptake ratio (UR) was calculated. Six patients in the active group underwent secondary imaging after anti-inflammatory treatment. Results the average octreotide UR in the orbits of the three groups were 1.40 ± 0.18, 1.15 ± 0.10 and 1.07 ± 0.20, respectively. The differences were statistically significant compared with the active group, the inactive group and the control group (all P<0.001); There was no statistically significant difference between the inactive group and the control group (P>0.05). There was a good correlation between UR and CAS of all patients with TAO (rall =0.859, P<0.001). There was a statistically significant difference between UR and CAS before and after treatment of patients in the active group (t =4.39, P =0.007). The difference between CAS before and after treatment was statistically significant (Z = -5.51, P<0.001), indicating that the score was decreased after treatment and the treatment was effective. Conclusion 99Tcm-octreotide orbital imaging can help clinicians judge the activity of inflammatory response of TAO, provide a basis for making treatment plan, and can be used for evaluation of curative effect.

Objective to establish an animal model of thyroid-associated ophthalmopathy (TAO) in homologous BALB/c mice immunized with human thyroid stimulating hormone receptor-activated splenocytes. Methods Twenty-three BALB/c mice were divided into two groups by completely randomized design: 18 mice in recombinant plasmid immunization group (group A) and 5 mice in empty plasmid immunization group (group B). They received recombinant plasmid pcDNA3.1/hTSHR and empty plasmid pcDNA3.1, respectively, and were immunized twice at the third and sixth weeks after immunization. All mice were sacrificed after 18 weeks, splenocytes were mechanically isolated, and orbital tissues were taken for pathological observation. Another 26 BALB/c mice were divided into two groups by completely randomized design: 16 mice in activated splenocyte immunization group (group C) and 10 mice in unactivated splenocyte immunization group (group D), respectively. All mice were sacrificed after 4 weeks, and orbital tissues were taken for pathological observation. Serum total thyroxine levels were determined by radioimmunoassay, and serum thyroid stimulating hormone levels were determined by immunoradiometry. Results Group A: About 25% of the mice had mucinous degeneration and edema in the orbital tissue, no obvious fibrous tissue and adipose tissue hyperplasia, and no degeneration and rupture of muscle fibers. Group C: About 50% of the mice had obvious mucinous degeneration and edema in the orbital tissue, local fibrous tissue and adipose tissue hyperplasia, and hyaline degeneration and rupture of muscle fibers; There was no morphological change in the orbital tissues of mice in group B and group D. Four weeks after splenocyte immunization, the total thyroxine in serum was significantly increased in group C (7.130 ± 1.017) μ g/dl compared with group D (6.431 ± 0.573) μ g/dl, and the difference was statistically significant (P =0.036). Serum thyroid stimulating hormone (TSH) in group C (0.070±0.032) μ IU/ml was significantly lower than that in group D (0.098±0.020) μ IU/ml, and the difference was statistically significant (P =0.020); There was no significant increase in serum TSR antibody in group C (0.202 ± 0.067) compared with group D (0.151 ± 0.055), and the difference was not statistically significant (P =0.055). Conclusion The animal model constructed by immunizing homologous BALB/c mice with splenocytes activated by human TSR is very close to the histological characteristics of human TAO, which is a feasible and effective method. TSR and T lymphocytes targeting this receptor play an important role in its autoimmune response.

Objective to study the difference of parapapapillary choroidal atrophy (PPA) in primary open-angle glaucoma (POAG), normal intraocular pressure glaucoma (NTG) and normal large depression eyes and its relationship with visual field. Methods the stereoscopic images of the optic head were measured by computer image analysis system, and the incidence and size of PPA were compared between 42 cases (42 eyes) of POAG, 40 cases (40 eyes) of NTG and 45 cases (45 eyes) of normal large depression eyes, and the correlation between the relevant parameters of PPA and the structural indexes of the optic head and the visual field grading was analyzed. The diopter (equivalent spherical power) of all enrolled patients ranged from +3.00 to-3.00 D. Results The incidence rates of α and β regions in normal large depression group, POAG group and NTG group were 85.4%, 100.0% and 95.0%, respectively, and 19.1%, 48.9% and 37.5%, respectively. The incidence rates of α and β regions in POAG group and NTG group were greater than those in normal large depression group, and the differences were statistically significant (P<0.05). The difference was statistically significant (P<0.05). There was no statistically significant difference in the area of α region between the three groups (Chi-Square =4.534, P =0.104). However, there was no statistically significant difference in the above indexes and the occurrence rate of α and β regions between POAG group and NTG group (P>0.05). The results of correlation analysis between the structural indexes of optic papilla and visual field in glaucoma patients showed that there was a strong correlation between the cup/disc ratio and the grade of visual field impairment (r =0.5624, P<0.01). However, there was a low correlation between the area of α region and the area of β region and the grade of visual field impairment (α region: r =0.246, P<0.01; β region: r =0.2302, P<0.01). The results of Logistic regression analysis of the factors related to the presence or absence of glaucoma visual field defect showed that only age and cup/disc ratio were confirmed as two possible influencing factors among the factors including age, sex, diopter, cup/disc ratio grading indexes and the presence or absence of α region and β region. Conclusion After excluding the moderate to high myopia population above-3.00 D, POAG There was no significant difference between the two groups of glaucoma patients, so it was concluded that PPA could not be used as an independent index for the diagnosis of POAG, nor as a differential diagnostic index between POAG and NTG.

Objective to investigate the effect of cell phone microwave on DNA damage of human lens epithelial cells (hLECs) and its effect on cell proliferation activity. Methods hLECs were divided into irradiated groups A, B, C, D and sham irradiation groups, and were irradiated continuously in sXc-1800 cell irradiation system for 2 h. The irradiation intensity [specific absorption rate (SAR)] of irradiated groups A, B, C, D was 1.0, 2.0, 3.0, 4.0 W/kg, respectively. Comet experiment was carried out 0.0, 0.5, 1.0 h after irradiation to detect the DNA damage and repair of cells. After microwave irradiation, bromodeoxyuridine (BrdU) was added to the culture solution, and the in situ detection kit of BrdU was used to observe the proliferation rate of cells after continued culture for 1 h. Results Compared with the sham irradiation group, the difference in DNA damage of cells in irradiated groups A and B was not statistically significant (P>0.05). The difference in DNA damage was statistically significant (P<0.01) in group C and D irradiated immediately after irradiation compared with that in group D irradiated sham (P<0.05). The difference was statistically significant (P<0.05) in group C irradiated immediately after irradiation (P>0.05), but the difference persisted (P<0.01) in group D irradiated immediately after irradiation (P<0.01). The results of BrdU in situ detection kit showed that there was no significant change in cell proliferation in irradiated group A, B and C (P>0.05), but the cell proliferation rate in irradiated group D decreased, and the difference was statistically significant (P<0.01). Conclusion The short-term acute action of 1.8 GHz cell phone microwave with SAR ≤3 W/kg did not produce or repairable damage to the DNA of hLECs cultured in vitro, nor did it affect the subsequent cell proliferation. The irradiation dose of 4.0 W/kg could cause irreversible DNA damage and decrease the cell proliferation rate.

Objective to investigate the effect of retinal glial cell-mediated hypoxic response molecular pathway on vascular endothelial precursor cells (EPCs) under hypoxic environment and its mechanism.Methods Human peripheral blood circulating EPCs (CD34+, CD33+ double label positive cells) were collected by fluorescence immunoactivation flow cytometry and then cultured; Human retinal glial cell growth medium with hypoxia (5% O2, experimental group) and normal oxygen (20% O2, control group) was used as conditioned medium respectively. EPCs were treated multiple times, and the proliferation activity (WST-1 colorimetric method) and differentiation ability (immunofluorescence staining method) of EPCs were detected and analyzed. The release of vascular endothelial growth factor (VEGF) was detected by enzyme-linked immunosorbent assay, and the expression of hypoxia responsive factor (HIF) -1 α in the nucleus was detected by immunoblotting. Results the proliferation activity (absorbance value was 1.53 ± 0.10) and differentiation ability [the number of cells was (29 ± 5)] of EPCs in the experimental group were significantly enhanced compared with the proliferation activity (absorbance value was 0.88 ± 0.25) and differentiation ability [the number of cells was (18 ± 8)] in the control group (P<0.05). The expression of HIF-1 α could be detected in the nucleus of EPCs in the experimental group after 6 and 24 hours of culture, but the expression of HIF-1 α was absent in the control group. The release of VEGF in the experimental group was significantly increased compared with the control group, and it was temporal, and the release of VEGF in the experimental group was increased by 44.88% compared with the control group [(220.28 ± 24.33) pg/ml] after 24 hours of culture (P<0.01). This effect is related to the activation of HIF-1 α and VEGF signaling channels in glial cells. In this study, the pathophysiological effects of glial cells on vascular precursor cells were investigated.

Objective to investigate the effects of blue light irradiation on apoptosis and mitochondrial membrane permeability transport of human retinal pigment epithelium (RPE) cells cultured in vitro.Methods Human RPE cells cultured in vitro with blue light irradiation.The experiment was divided into three parts: the first part was divided into three groups with different illuminations: the first group was (500±100) lx, the second group was (2000±500) lx, and the third group was (3000±500) lx; The RPE cells were divided into three groups with the same illumination and different illumination times, the first group was irradiated for 6 h, the second group was irradiated for 12 h, and the third group was irradiated for 24 h. The illumination was (2000±500) lx; The measurement of mitochondrial membrane potential was also divided into three groups, the first group was exposed to 3 h, the second group was exposed to 6 h, and the third group was exposed to 12 h, and the illuminance was (2000 ± 500) lx. Part III: the same illuminance and exposure time, the illuminance was (2000 ± 500) lx, and the exposure time of RPE cells was 6 h; Different termination time of cell culture were divided into 4 groups. The termination time of cell culture in group 1 was 6 h after light irradiation, group 2 was 12 h after light irradiation, group 3 was 24 h after light irradiation, and group 4 was 36 h after light irradiation. The apoptosis of RPE cells was observed by terminal deoxyribonucleic acid transferase-mediated in situ nick end labeling (TUNEL) staining, fluorescein-labeled Annexin V-FITC and PI double staining flow cytometry, transmission electron microscopy, etc. Human RPE cells were incubated with Rhodamine 123 fluorescent dye, and the mitochondrial membrane potential was detected by flow cytometry, the activity of cytochrome C was measured by enzyme-linked immunoassay, and the activity of Caspase-3 was measured by colorimetric assay.Results In the second part, the volume of TUNEL-positive cells in the first group decreased and became rounded, the nucleus was condensed, the edges were aggregated into crescent shape or cap shape, the nucleus was fragmented into several pieces, and the cell membrane exited the cell.The mitochondria were swollen, the ridge of mitochondrial inner membrane disappeared, the rough endoplasmic reticulum expanded, and the lysosomes increased by transmission electron microscopy. With the increase of light intensity, apoptosis, apoptosis secondary necrosis and necrosis appeared in RPE cells, and the mitochondrial membrane potential decreased gradually. The percentage of apoptosis of secondary necrotic cells and necrotic cells increased after 24 hours of light exposure, and the percentage of apoptosis of RPE cells increased gradually at 6 and 12 hours after the third part of light exposure; The percentage of necrotic cells and necrotic cells secondary to apoptosis increased significantly at 24 and 36 h after irradiation, and the fluorescence intensity of RPE cells decreased significantly at each time point after irradiation. The concentration of cytochrome C in the two groups increased significantly at 24 and 36 h after irradiation, but no change of Caspase-3 activity was detected. Conclusion Blue light irradiation can lead to apoptosis, apoptosis secondary necrosis and necrosis of human RPE cells cultured in vitro, and the degree of damage is related to the illumination and time; The injury process of cultured human RPE cells caused by blue light irradiation was related to the decrease of mitochondrial membrane potential and the release of cytochrome C; Mitochondrial membrane potential can be used as an early indicator to detect the apoptosis of human RPE cells induced by blue light.

Objective to investigate the changes of mitogen-activated protein kinase (MAPK) signal transduction pathway in human retinal pigment epithelial (RPE) cells coated with magnetic beads under the action of magnetic field. Methods the collagen-coated magnetic bead suspension was added to human RPE cells cultured in vitro and incubated, and the cells attached to the magnetic beads were placed in a constant magnetic field. The expressions of extracellular signal-regulated kinase (ERK), c-jun aminoterminal kinase (JNK) and p38 signaling molecule of MAPK and the intervention effect of p38 specific blocker (SB203580) were detected by immunoblotting. The expression of activated p38 was observed by immunofluorescence staining. Results in RPE cells, total ERK, JNK and p38 were expressed, activated ERK and p38 were also expressed, but activated JNK was not expressed. The expression of activated ERK was not significantly changed, but the expression of activated p38 was very low before the action of magnetic field. The phosphorylation of activated p38 was significantly increased after 5 min of action. SB203580 could inhibit the phosphorylation of activated p38 caused by pulling action. Immunofluorescence staining also showed that pulling stimulation could increase the fluorescence of activated p38. Conclusion Magnetic field can exert an effect on RPE cells coated with magnetic beads, and part of the effect may be produced by p38 signal transduction pathway.

Objective to investigate the expression of muscarinic type 1 (M1) receptor in normal human retinal pigment epithelium (RPE) cells and the role of M1 receptor in maintaining the function of RPE cells and its relationship with the occurrence and development of myopia. Methods Cell culture strains were established by the established isolation and culture methods of RPE cells. The well-growing cells were collected from 3 to 5 generations, and the expression of M1 receptor in cultured RPE cells was detected by reverse transcription polymerase chain reaction (RT-PCR) and indirect immunofluorescence (IIF). Results the cultured RPE cells were polygonal, the average division time was about 2 to 3 days, and the cells contained brown-yellow pigment particles. With the division of the cells, the pigment particles in the cells diluted and decreased. RT-PCR and indirect immunofluorescence assay showed that the expression of M1 receptor in human RPE cells in vitro was detected. Conclusion the distribution of M1 receptor in human RPE cells was observed. M1 receptor plays an important role in maintaining the function of RPE cells. The mechanism of M1 receptor antagonist injection into vitreous body to delay the occurrence and development of myopia may be related to its inhibition

Objective to investigate the gene mutation loci of congenital aniridism families.Methods 2~5 ml of peripheral blood of family members were extracted and DNA was extracted; Firstly, two polymorphic microsatellite genetic markers (D11S904 and D11S935) were synthesized by polymerase chain reaction (PCR). The PCR products were denatured and separated by denatured polyacrylamide (PAGE) gel. According to the relationship between band pattern and family members, haplotype linkage analysis was performed to determine whether the iris-free phenotype of the family was related to PAX6 gene. All exons of PAX6 gene were amplified by PCR, and all PCR products were analyzed by single-strand conformational polymorphism (SSCP) respectively. The mutated exons were determined by the difference of banding patterns between patients and normal people, and the mutated sites were found by direct DNA sequencing of PCR products with different SSCP banding patterns. Results the congenital aniris phenotype in this family was clearly linked to PAX6 gene; The PCR product of exon 9 of PAX6 gene was analyzed by SSCP, which showed that all patients had abnormal band pattern, but none of normal people had this abnormal band pattern. Sequencing results showed that the mutation site was T in nucleotide C of exon 9 c1080 of PAX6 gene, and the codon encoding arginine was mutated to stop codon. Conclusion PAX6 gene mutation can lead to congenital aniris.

With the popularization of intraocular lens implantation, phakic anterior chamber intraocular lens implantation has attracted widespread attention to correct high myopia and hyperopia, and anterior chamber intraocular lens implantation has become a remedy for the impossibility of posterior chamber intraocular lens implantation. However, there are many postoperative complications in anterior chamber intraocular lens implantation, and one of the main reasons for these complications is the inappropriate lens size. Therefore, accurate biometric measurement of anterior chamber diameter is very important.

Cornea preservation by organ culture method is one of the main methods for preserving corneal donor materials, which has been widely used in many eye banks in Europe and America [1-3]. The traditional preservation method is to connect corneal slices with silicone bottle caps by sutures, and make the corneal slices hang in 100 ml infusion glass bottles [4] (Figure 1). This method has the shortcomings of complicated operation, easy contamination and inability to dynamically observe corneal quality during preservation.

The metastases of thyroid carcinoma were mostly in the liver, lung, bone and central system [1], and the metastases to the orbit were less common. The orbital metastases were more common in breast cancer and lung cancer [2]. A case of thyroid carcinoma metastasized to the orbit and intracranial was reported. The histomorphology of the metastasis was "benign", which was rare in clinic.

She was a 6-year-old female with inward displacement of her left eye and visual acuity decreased for about 40 d. Two months ago, she was pecked by a chicken on the lateral side of her left orbit. Subsequently, a tumor gradually rose under the skin of the pecked area, and her left eye was displaced inward with visual acuity decreased. She went to our ophthalmology department on October 15, 2004 and was admitted to the hospital with "left orbital tumor".

Fabry disease [1], also known as Anderson-Fabry disease, is an X-sex-linked recessive neurosphingolipid metabolism disease. Because of the deficiency of α-galactosidase A (α-Gal A) in lysosomal hydrolase, the activity of lysosomal hydrolase in tissues and body fluids of male patients is reduced, resulting in the failure of degradation of glycosphingolipids (mainly trihexosoylsphingosine) with α-galactose terminals, which are widely deposited in lysosomes of body fluids, vascular endothelial cells, epidermal cells and smooth muscle cells.

A 16-year-old male patient came to our hospital on September 4, 2004 because of the gradual decrease of visual acuity in both eyes (uncorrectable) for 2 years. Two years ago, the patient felt that the visual acuity in both eyes was decreased, and it could be corrected to 0.8 with glasses (-1.00 DS). One year ago, he felt that the vision was blurred when he wore glasses, and the corrected visual acuity was unknown when he wore glasses again (-2.00 DS). Six months ago, the visual acuity was 0.3 after wearing glasses (-13.00 DS); the visual acuity continued to decrease since then.

The patient was a 37-year-old male who came to our hospital on August 7, 2005 due to exophthalmos of both eyes for 11 months and a significant decrease in visual acuity of his right eye for 1 month. Eleven months ago, the patient was diagnosed with hyperthyroidism in the local hospital due to rapid heart rate and overeating. After drug treatment, his condition was controlled, but both eyeballs gradually prominent. After treatment, he was considered to be thyroid-related ophthalmopathy in both eyes. After treatment, the ocular symptoms did not improve significantly, both eyeballs were highly prominent, the left eye underwent enucleation due to exposed keratitis and corneal perforation, and the right eyelid underwent partial palpebral cleft suture due to incomplete closure.

thyroid associated ophthalmopathy (TAO) is the most common clinical disease with unilateral or bilateral exophthalmopathy, and the pathogenic mechanism is still unknown. Graves first described the clinical manifestation of goiter in 1853, so most scholars called it Graves disease [1].

The 3rd Global Chinese Ophthalmology Academic Conference and the 11th National Ophthalmology Academic Conference of Chinese Medical Association (The 3rd Global Chinese Ophthalmic Conference in conjunction with the 11th Congress of Chinese Ophthalmological Society) It was held in Beijing International Convention Center from August 31 to September 4, 2006.

The 3rd Global Chinese Ophthalmology Congress and the 11th National Ophthalmology Congress of Chinese Medical Association were held in Beijing from August 31 to September 4, 2006, which aroused strong response from the ophthalmology academic circles at home and abroad, and were highly praised by well-known peers.