The human hereditary retinal degeneration is one of the main cause of irreversible blindness in the world. the mechanisms leading to retinal photoreceptor degeneration are not entirely clear. However, microglia acting as innate immune monitors are found to be activated early in retinal degeneration in many retinitis pigmentosa animal models. These activated microglia are involved in phagocyte rod cell fragments of degenerated retina, and also produce high levels of cytotoxic substances such as pro-inflammatory cytokines and chemokines, which aggravate the death of adjacent healthy photoreceptor cells. It suggests that microglia activation plays an important role in photoreceptor degeneration. At the same time, a series of studies have confirmed that some drugs can prevent or reduce neuronal death and slow the occurrence and progression of retinal degeneration by interfering with abnormal activation of microglia. It is expected to be a new choice for the treatment of hereditary retinal degeneration.
Objective To detect the value of three-dimensional (3D) ultrasound diagnosis in common ocular fundus diseases. Methods Two-dimensional (2D) images of 38 patients with common ocular fundus diseases were three-dimensionally reconstructed via 3D ultrasound workstation. The 3D images reflecting the ocular diseases were analyzed. Result In 38 patients with common ocular fundus diseases, there was vitreous hemorrhage in 16 patients, retinal detachment in 12, choroidal detachment in 5, and intraocular space occupying lesion in 5. Compared with the 2D images, 3D reconstructed images reflect the lesions more intuitionistically, displayed the relationship between the lesions and the peripheral tissues more clearly, and revealed the blood flow more specifically. During a scanning examination, 3D reconstructed technology provided the diagnostic information of section of X, Y and Z axises simultaneously which shortened the time of examination; the condition of any point of lesions and the relation between the lesion and the peripheral tissues could be gotten by the tools like cut and chop provided by 3D imaging software itself, which avoided detecting the same lesion with different angles and lays and proved the diagnostic efficacy. Conclusions 3D ultrasound diagnosis is better than 2D in diagnosis of vitreous, retina, choroid, and intraocular space occupying lesion. 3D ultrasound diagnosis is a complementarity for the 2D one, and the Z axis changes the former observational angles which may provide the new way of precise diagnosis. (Chin J Ocul Fundus Dis, 2005, 21: 381-383)
Objective To observe the clinical features, phenotypes and genotypes in a Chinese family with choroideremia (CHM). Methods A Chinese four-generation family (15 members) with CHM, including 5 patients (4 males/1 female), 2 female carriers and 8 healthy members, was enrolled in this study. Initially all family members underwent best corrected visual acuity (BCVA), indirect ophthalmoscopy, fundus fluorescein angiography, optical coherence tomography (OCT), visual field and full view electroretinogram (ERG). BCVA was followed up for 3 years. Venous blood samples were collected, and all of the 15 coding exons and flanking intron regions were amplified in the proband by polymerase chain reaction followed by direct sequencing. Protein structure was modeled based on the protein data bank and mutations in DeepView v4.0.1 to predict the effect of the mutations. A total of 180 healthy volunteers were enrolled as control group to matching CHM gene sequences. Results The visual acuity (VA) of 3/4 adult male patients began to decrease at less than 10, 10 and 30 years old, the average BCVA was 0.43. There were characteristic signs and symptoms of CHM including narrow visual field, extinguished rod and cone response in ERG, disappeared junction line and intermediate line of photoreceptor inner segment/outer segment on OCT. After 3 years, the mean BCVA decreased to 0.11. The BCVA of one young male patient was 1.0 in both eyes with minor changes fundus and visual field. The VA of the female patient began to decrease at 50 years old, her BCVA of two eyes were 0.5 and 0.25, respectively. The fundus changes were typical of CHM, with relative scotomas in the peripheral visual field of OD, and big scotomas in the OS. After 3 years, her mean BCVA decreased to 0.2. Of 2 female carriers, one had minor fundus changes (patches of pigmentary deposits, atrophy spots of retinal pigment epithelium cells), and the other was normal. A novel heterozygous c.1837G＞A mutation in exon 15 of CHM was detected in the proband, which resulted in the substitution of serine by proline at codon 613 (p.D613N). Based on molecular modeling, the misfolded protein caused by the mutation might destabilize the structure of the helix that potentially could affect the global stability of the Rep-1 protein. Conclusions A novel c.1837G＞A (p.D613N) mutation may be the causative mutation for CHM in this family. Female CHM carriers may have some signs and symptoms.
ObjectiveTo evaluate macular microvessel changes in familial exudative vitreoretinopathy (FEVR) by optical coherence tomography angiography. MethodsCross-sectional clinical case-control study. From November 2019 to November 2020, 21 FEVR patients (41 eyes) from Weifang Eye Hospital were selected; 17 healthy volunteers (28 eyes) with the same age and gender as FEVR group were selected as normal control group. According to the best corrected visual acuity (BCVA) 1.0 and ＜1.0, FEVR group was divided into normal visual acuity group (27 eyes) and visual acuity decreased group (14 eyes). All enrollees received BCVA and OCTA. BCVA was performed with an international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) vision. The OCTA instrument was used to scan the macular area of all the examined eyes in the range of 3 mm×3 mm, 6 mm×6 mm, and the blood vessel density (VD) and blood perfusion density (PD) within the range of 3 mm×3 mm, 6 mm×6 mm were measured and the area, circumference, and morphological index of the foveal avascular zone (FAZ) within the range of 6 mm×6 mm. Quantitative data were compared between groups by independent sample t test. Statistical data were compared by χ2 test. The area under curve (AUC) of each index was determined according to receiver operating characteristic curve (ROC curve), and the predictive value of each index was evaluated. ResultsIn the macular area of 6 mm×6 mm, VD, PD, FAZ area and FAZ perimeter of FEVR group were all lower than those of normal control group, and the differences were statistically significant (t=−3.350, −2.387, −3.519, −3.029; P＜0.05). In macular area of 3 mm×3 mm and 6 mm×6 mm, compared with normal vision group and vision loss group, both VD and PD decreased. The differences were statistically significant (t=2.088, 2.114, 2.160, 2.545; P＜0.05). In the macular area of 6 mm×6 mm , the FAZ morphological index of the two groups was significantly different (t=2.409, P＜0.05). ROC curve analysis showed that all the indicators had low diagnostic value for FEVR (AUC＜0.5). ConclusionThere are microvascular abnormalities in macular area in FEVR patients, and the decrease of blood vessels and the change of FAZ shape may be related to the loss of visual acuity.
Rapid development of recently emerging precision medicine techniques represented by gene therapy has brought hope for the treatment of rare blinding eye diseases such as inherited retinal diseases (IRDs) for which there was no effective treatment previously. Although the globally growth of clinical trials for IRDs has increased rapidly over the past decade, due to the highly genetic and clinical phenotypic heterogeneity, as well as limited data on epidemiology and natural history of the disease, along with severe loss of vision function of majority patients for which the established measurements may not be appropriate, such studies lack standard outcome measurements and endpoints to asses clinical meaningful effectiveness, posing great challenges in terms of study design and evaluation of treatment efficacy, as well as clinical practice application. At present, there is no systematic nor standardized guidance on safety measures, clinical outcomes and endpoints of visual function for clinical trial design in IRDs. Therefore, in order to standardize the validated evaluation of IRDs clinical efficacy outcome measurements and endpoints, the Fundus Disease Group of Chinese Medical Association Ophthalmology Branch and Fundus Disease Committee of Chinese Medical Doctor Association Ophthalmology Branch organized domestic experts to put forward consensus and recommendations on standardizing outcome measurements and endpoints for clinical study design in IRDs, aiming to advance the study design of IRDs natural history research and clinical trials and to effectively evaluate disease progression and intervention efficacy. Along with the development of medical science and clinical trials, relevant content will be improved and updated accordingly.
Inherited retinal diseases (IRDs) are a group of severe retinal degenerative diseases leading to permanent visual impairment. IRDs are the major cause of irreversible blindness in children and working age groups. Gene therapy is a new clinical treatment method and currently the only clear and effective treatment for IRDs, while, there are still risks in clinical research and application. How to standardize perioperative management and reduce the potential risks of treatment is one of the keys to ensure the safety and effectiveness of treatment. However, there is no systematic and standardized guidance on the perioperative management for IRDs gene therapy. Therefore, in order to standardize the perioperative management, the Fundus Disease Group of Ophthalmology Society of Chinese Medical Association and Chinese Medical Doctor Association organized domestic experts to put forward standardized opinions on the perioperative management of IRDs gene therapy in China after repeated discussion and combined with domestic and foreign research experience, so as to provide clinicians with reference and application in clinical research and practice.
ObjectiveTo explore the light response, retinal inflammation and apoptosis of the retinal ganglion cells (RGCs) 1 year after the new type of channelrhodopsin PsCatCh2.0 was transfected into the retina of rd1 mice. MethodsTwenty-four male rd1 mice were randomly divided into rd1 experimental group and rd1 control group, 12 mice in each group. 1.5 μl of recombinant adeno-associated virus (rAAV)2/2-cytomegalovirus (CMV)-PsCatCh2.0-enhanced green fluorescent protein (EGFP) was injected into the vitreous cavity 1 mm below the corneoscleral limbus of mice in the rd1 experimental group, and the same dose of recombinant virus was injected 2 weeks later at temporal side 1 mm below the corneoscleral limbus. One year after virus injection, the light response of RGCs expressing PsCatCh2.0 was recorded by patch clamp technique; the expression of PsCatCh2.0 in the retina was evaluated by immunofluorescence staining; the transfection efficiency of recombinant virus was evaluated by the transfection efficiency of virus and the number of RGCs. Hematoxylin-eosin staining was performed to measure the inner retinal thickness. Western blotting was used to detect the protein expression of nuclear factor (NF)-κB p65 in retina; real-time quantitative polymerase chain reaction was used to detect the relative expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and Bax mRNA. Terminal deoxynucleotidyl transferase kit was used to observe the apoptosis of retinal cells in each group of mice. ResultsOne year after the intravitreal injection of recombinant virus, PsCatCh2.0-expressing RGCs can still generate 30 pA photocurrent. The virus PsCatCh2.0-EGFP was mainly transfected into RGCs, and partly transfected into amacrine cells, almost no transfection was seen in bipolar and horizontal cells. There were no significant differences in the number of RGCs and thickness of the inner retina between the rd1 experimental group and the rd1 control group (F=14.35, 0.05; P＞0.05), while the rd1 experimental group NF-κB p65 protein expression, TNF-α and IL-6 mRNA quantification were significantly lower than those of rd1 control group (F=4.61, 5.91, 5.78; P＜0.05). The number of red fluorescent apoptotic cells in the retina of mice in the rd1 experimental group was less than that in the rd1 control group, and the Bax mRNA expression was lower than that in the rd1 control group, and the difference was statistically significant (F=7.52, P＜0.01). ConclusionOne year after intravitreal injection of recombinant virus, the PsCatCh2.0 expressing RGCs can still generate photocurrent. Long term transfection and expression of PsCatCh2.0 has no obvious cytotoxic effect on RGCs, nor it increases the inflammatory effect of the retina of rd1 mice with retinal degeneration.
Inherited eye disease is a heterogeneous group of eye disorders caused by genetic defects, which has many genetic characteristics, such as multiple inheritance modes and numerous gene variation types. Over the past few decades, genetic testing has improved significantly, with more and more known disease-causing gene variants identified. With the rapid development of high-throughput sequencing technology, clinical diagnosis and treatment of eye genetic diseases have been accelerated, and molecular diagnosis of eye genetic diseases has become an important step in accurate diagnosis and treatment. How to correctly select and evaluate each kind of genetic testing technology, reasonably standardize the use of genetic testing technology, and provide patients with more accurate genetic counseling are problem that clinicians need to seriously consider.
Objective To observe the changes of intraocular pressure (IOP) after intravitreous injection wih triamcinolone acetonide (TA) and their affected factors. Methods The clinical data of 125 patients (125eyes) who had undergone intravitreous injection with TA were retrospectively analyzed. The patients (52 males and 73 females) aged from 17 to 83 years with the average age of 56.5. There were 49 patient (39.2%) with diabetic retinopathy (DR), 56 (44.8%) with retinal vein occlusion (RVO), and 20 (16.0%) with exudative age-related macular degeneration (AMD). One day before the treatment, IOP was measured by Goldmann applanation tonometry, and the basic IOP was 7~31 mm Hg (1 mm Hg=0.133 kPa) and the average IOP was (14.69plusmn;3.72) mm Hg. The patients were divided into two groups according to the basic IOP:below 15 mm Hg group (n=64) and 15 mm Hg or above group (n=61). All of the patients underwent intravitreous injection with 4mg TA. IOP was measured 1 day, 3 days, 1 week, 2 weeks, and 1 month after the treatment in the same way, respectively, and later was measured once every 1 month. The follow-up period was 3~21 months with the mean of 5 months. The elevation of IOP would be defined as the pressure of 21mmHg or higher. The changes of IOP in patients before and after the treatment, and with different diseases and ages were analyzed. Results Thirty-six patients (28.8%) had elevation of IOP after the treatment, out of whom 97.2% had the elevation within 3 months after the injection and decreased to the basic level 7 months after the injection. In these patients, there were 11 (17.19%) in the below 15 mm Hg group and 25 (40.98%) in 15 mm Hg or above group, and the difference between the two groups was statistically significant (P＜0.01）. During the followup period, the mean maximum IOP was (20.09plusmn;7.58) mmHg, which was 5.43 mmHg higher than that before the treatment（P＜0.001）. The mean maximum IOP of 53 patients (42.4%) after the treatment was 5 mm Hg higher than that before the treatment. The mean maximum IOP during the followup period was （18.19plusmn;4.73）mmHg in DR group，（22.50plusmn;9.30）mmHg in RVO group, and（18.12plusmn;6.09）mmHg in AMD group. The occurrence of the elevation of IOP in RVO group was obviously higher than that in the other 2 groups (P＜0.01）. The result of regression analysis showed that age was correlative with the elevation of IOP after the treatment: more risks of occurrence of high IOP were found in younger patients (P=0.000). Conclusion Elevation of IOP after intravitreous injection with TA is common, which is correlative with the basic IOP, age, and pathogeny. After the intravitreous injection with TA, the elevation of IOP often occurs in patients with high basic IOP before treatment, younger age, and RVO. (Chin J Ocul Fundus Dis, 2007, 23: 115-117)
Objective To evaluate the diagnostic value of panoramic 200 scanning laser ophthalmoscope for retinal detachment. Method Images of ocular fundus of the patients with retinal detachment were obtained by panoramic 200 scanning laser ophthalmoscopy, which were compared with the results of binocular indirect ophthalmoscopy (BIO). The extent of the retinal detachment, the occurrence of retinal hole or not, and the proliferation were observed. Any discrepancies of the results of the two methods were then analyzed. Results In the images from 75 eyes of 71 patients with retinal detachments which were obtained by panoramic 200 scanning laser ophthalmoscopy, recurrent retinal detachments was found in 3 patients (3 eyes), single retinal detachment was in 13 patients (16 eyes) inc luding intercurrent retinal cyst in 1 patient (1 eye), intercurrent retinal hole was in 43 patients (43 eyes), and intercurrent pre-or sub-retinal proliferation was in 14 patients (15 eyes) (4 eyes having retinal hole simultaneously). The results of panoramic 200 scanning laser ophthalmoscopy and BIO were accordant in 53 patients (56 eyes) and inconsistent in 18 patients (19 eyes) due to the loss of peripheral small retinal holes by panoramic 200 scanning laser ophthalm oscopy. The results of the follow-up examination of 16 patients were accordant with the clinical records. Conclusion Panoramic 200 scanning laser ophthalmoscope has the advantages of non-mydriasis, speediness, and wide view field, and can save external records and provide high-resolution images; it is a valuable diagnosis method for retinal detachment. (Chin J Ocul Fundus Dis, 2006, 22: 317-320)