Table of Content

25 January 2022, Volume 31 Issue 1

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Gene therapy targeting glaucoma: reality and challenge

Liu Guo, Tan Junkai, Zhu Xianjun, Liu Xuyang

2022, 31(1):  1-7.  doi:10.13281/j.cnki.issn.1004-4469.2022.01.001

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Primary glaucoma is a kind of multigenic complex hereditary disease affected by environmental factors. The gene therapy strategy for glaucoma can not correct or compensate for a single pathogenic gene only, but at present, gene therapy can still show “palliative” results such as actively delaying the onset, reducing or releasing symptoms. The current gene therapy strategies for glaucoma include gene therapy targeting the cytoskeleton regulatory protein of trabecular meshwork, gene therapy targeting the uveoscleral aqueous humor outflow channel, both of which mainly increase aqueous humor outflow and gene therapy targeting the ciliary epithelium, which mainly reduces aqueous humor production. In addition, anti-cicatricial gene therapy after trabecular surgery (such as transducing the metalloproteinase-3 gene into the operation area), retinal neuroprotective gene therapy [including improvement of retinal ganglion cell (RGC) nutrition by expressing brain-derived neurotrophic factor and activating neurotrophin receptor in the inner retina, exogenous expression of anti-apoptotic gene factors to antagonize RGC apoptosis, immune regulation to reduce RGC apoptosis, regulating glial cell function to support RGC, reducing reactive oxygen species (ROS), to antagonize RGC apoptosis, etc.]. However, the viral vectors still show risks more or less. It is an effective solution modifying the transgenic vectors to achieve accurate and specific targeted expression, which is also the key to promote the practicability of glaucoma gene therapy technology. In addition, how to maintain long-term expression and increase the effective therapeutic period is also a challenge for glaucoma gene therapy. (Ophthalmol CHN, 2022, 31: 1-7)

Subtype distribution and demographic characteristics of open-angle glaucoma in multi-level specialist clinics

Pang Ruiqi, Wang Yue, Fan Sujie, Zeng Liuzhi, Sun Yunxiao, Guo Yiqin, Li Ruyue, Cao Kai, Wang Ningli

2022, 31(1):  8-13. 

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Objective To analyze the distribution of disease subtypes and patient demographic characteristics of open-angle glaucoma (OAG) in multi-level glaucoma clinics of China. Design Retrospective case series. Participants 586 OAG patients in the glaucoma specialty clinic. Methods The diagnosis and treatment data of glaucoma specialist outpatients in Beijing Tongren Hospital (major ophthalmological center), Chengdu Integrated TCM & Western Medicine Hospital (minor ophthalmological center, group A) and Handan City Eye Hospital (minor ophthalmological center, group B) from September 2018 to February 2020 were collected. The disease subtype, gender, age and place of origin for all OAG patients were recorded. Main Outcome Measures Demographic characteristics and OAG subtype composition ratio. Results This study recorded 9584 visits of diagnosis and treatment data, and included 586 OAG patients, with an average age of 52.35±16.48 years old, and males accounted for 59.7%. Among the subtypes of OAG patients, 429 patients with primary open-angle glaucoma (POAG), accounting for 73.2%, with an average age of 51.74±16.61 years old, and more male patients, reaching 61.8%. There were 108 patients with normal-tension glaucoma (NTG), accounting for 18.4%, and the average age was 54.97±15.31 years old. Both male and female patients were 50.0%. There were 49 patients with secondary OAG, accounting for 8.4%. Compared with major ophthalmological center, the proportion of NTG in minor ophthalmological center is lower (23.0% vs. 10.6%, X2=14.06, P<0.01), and the proportion of secondary OAG is higher (5.1% vs. 13.8%, X2=13.42, P<0.01). The proportion of local patients in the major ophthalmological center was 26.8%, which was much lower than that of the minor ophthalmological center (90.8% in group A, X2=110.58, P<0.01; 96.5% in group B, X2=96.97, P<0.01). Conclusion In the glaucoma specialist clinic, the gender and age characteristics of OAG patients are similar to the past population-based survey data, and the proportion of NTG patients is lower than the results of the past population-based data. Major ophthalmological center has a higher proportion of patients from other provinces and cities, with more NTG patients and fewer secondary OAG patients than minor ophthalmological center. (Ophthalmol CHN, 2022, 31: 8-13)

The preliminary study on long-term efficacy of penetrating canaloplasty in glaucoma 

Ye Wenqing, Gu Juan, Hu Cheng, Cheng Huanhuan, Deng Yuxuan, Zhang Shaodan, Xie Yanqian, Le Rongrong, Liang Yuanbo

2022, 31(1):  14-19.  doi:10.13281/j.cnki.issn.1004-4469.2022.01.003

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 Objective To evaluate the long-term efficacy and safety of penetrating canaloplasty for glaucoma. Design Retrospective case series. Participants Consecutive cases of 15 glaucoma patients (16 eyes) with penetrating canaloplasty at the Eye Hospital of Wenzhou Medical University from June 2015 to December 2015 were collected. Methods The preoperative demographic characteristics and postoperative intraocular pressure (IOP), glaucoma medications and other information were reviewed. Surgical success was defined as IOP ≤21 mmHg with or without glaucoma medications (qualified success) and without any glaucoma medications (completes success). Main Outcome Measures IOP, number of glaucoma medications, surgical success rate, complications and filtering bleb status. Results A total of 15 glaucoma patients (16 eyes) achieved the successful 360-degree catheterization of the canal with 7 males which were included to analyze. The mean age was (48.9±16.0) years old, and the mean preoperative IOP was (37.9±11.4) mmHg with the median medication number of 3 (2, 4). The mean postoperative IOP was (17.2±6.0), (15.9±4.5), (14.4±2.2), (13.0±1.8), (13.7±3.2), (12.9±2.9), (15.6±3.1), and (14.5±2.7) mmHg at 1 month, 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months, respectively. There was significant difference in IOP between postoperative and preoperative. The median medication number (range) was 0 (0, 1.5) at 1 month and 0 at the rest follow-up time, respectively. There was significant difference in the number of medications between postoperative and preoperative. The complete success rate at 36 months and 60 months were both 81.3%. Intraoperative and postoperative complications were observed in 11 eyes (68.8%) of 16 eyes, mainly including IOP spike (43.8%) and hyphema (37.5%). 13 eyes (81.3%) had no obvious filtering bleb. Conclusions The penetrating canaloplasty is a new internal drainage surgery for glaucoma with stable long-term efficacy, but need to be observed in a larger sample. (Ophthalmol CHN, 2022, 31: 14-19)

Comparison of iris and ciliary biometry parameters between eyes of primary angle closure glaucoma and primary angle closure suspects

Wang Linhao, Wang Junming, Deng Chaohua

2022, 31(1):  20-25.  doi:10.13281/j.cnki.issn.1004-4469.2022.01.004

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Objective To observe the differences of anterior segment biometry parameters between primary angle closure glaucoma(PACG) and primary angle closure glaucoma suspects(PACS). Design Retrospective comparative case series. Participants 58 patients with PACG/PACS who were diagnosed from October, 2019 to Mrach, 2021 at Wuhan Tongji Hospital. Methods Medical records of all patients were reviewed including ultrasound biomicroscopy (UBM). Qualitative and quantitative comparison of biometry parameters between PACG/PACS groups were conducted. Main Outcome Measures  anterior chamber depth (ACD), angle opening distance 500(AOD500), trabecular-iris angle 500(TIA500), trabecular-ciliary process distance 500(TCPD500), trabecular-ciliary process angle(TCA), iris thickness 500 (IT500）, ciliary process length(CPL), ciliary body thickness(CBT). Result Compared with PACS group (n=25), PACG group (n=33) had lower best corrected visual acuity (BCVA) (0.4±0.35, 0.2±0.17), higher baseline intraocular pressure (21.17±6.09, 15.57±3.57 mmHg), shorter ocular axis (22.17±1.22, 22.74±0.88 mm), shallower ACD (1.77±0.27, 1.94±0.25 mm), and AOD500, TIA500, TCPD500 TCA500 is smaller (0.04±0.04, 0.10±0.05 mm; 3.90±4.58, 11.07±4.77 °; 0.51 ± 0.10, 0.58±0.10 mm; 60.55±13.26, 71.54±12.58 °, respectively) and CPL is longer (1.43±0.26, 1.28±0.15 mm). The proportion of iris insertion point at the base of ciliary body (54.5%, 20.0%) and ciliary body pronation (68.0%, 39.4%) in PACG group was greater than that in PACS group (all P<0.05). There was no statistically significant difference in IT500, CBT and proportion of iris angulation and iris convexity between PACG group and PACS group. Conclusion Smaller AL, shallower anterior chamber depth, more significant the anterior rotation and size of the ciliary body, and larger proportion of the basal iris insertion in PACG group than in PACS group were observed, whether these features be risk factors of PACG progression, remains to be determined by long term follow-up observation. (Ophthalmol CHN, 2022, 31: 20-26)



Incidence and risk factors of intraocular pressure elevation within postoperative three days in retinal detachment patients treated by pars plana vitrectomy with silicone oil tamponade

Xue Cancan, Li Shushan, Miao Jinhong, Zhang Chun

2022, 31(1):  26-32.  doi:10.13281/j.cnki.issn.1004-4469.2022.01.005

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Objective To investigate the incident rate and risk factors of intraocular pressure(IOP) elevation within 3 days afterpars plana vitrectomy and silicone oil tamponade for retinal detachment. Design Prospective case series. Participants 135 cases of retinal detachment patients who were treated by vitrectomy with silicone oil tamponade from February to August 2018 in Peking University Third Hospital were consecutively included. Methods IOP at hours 2, 4, 6~8, and days 1, 2, 3 after surgery were recorded. IOP≥25 mmHg at any time was defined as IOP elevation. Survival time was defined as the time interval (hours) from the end of vitrectomy to the onset of the first IOP elevation. Cox regression analysis was used to evaluate the risk factors associated with postoperative IOP elevation. Kaplan-Meier survival curves were constructed to visualize the probability of overall survival of patients with different etiology of retinal detachment. Main Outcome Measures Incidence and risk factors for IOP elevation. Results Among 135 patients enrolled, 44 (32.6%) patients developed IOP elevation, with the incident rate peaked at the postoperative day one (20.2%). The etiology of retinal detachment was significantly associated with the IOP elevation (P=0.006). Compared to primary rhegmatogenous retinal detachment, patients with diabetic tractional retinal detachment and recurrent retinal detachment had 3.5 (P=0.002, hazards ratio (HR) =3.41) and 3 (P=0.010, HR=2.91) folds of increased risk for IOP elevation. The overall survival probability of diabetic traction retinal detachment and recurrent retinal detachment was significantly lower than that of primary rhegmatogenous retinal detachment and traumatic retinal detachment (all P<0.05). Conclusion Early-onset IOP elevation occurs in one-third of retinal detachment eyes with silicone oil tamponade, with the incidence peaked at the first postoperative day. The first postoperative day visit, at least IOP examination, is still necessary for eyes underwent vitrectomy and silicone oil tamponade, especially those with diabetic tractional retinal detachment and recurrent retinal detachment. (Ophthalmol CHN, 2022, 31: 27-32)

Experimental research on the relationship between the distribution of pigment particles in aqueous outflow channel and intraocular pressure in DBA/2J mice

Pu Liping, Tang Qi, Tian Junqi, Qing Guoping

2022, 31(1):  33-38.  doi:10.13281/j.cnki.issn.1004-4469.2022.01.006

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Objective To investigate the relationship between the morphology, size, and quantity of pigment particles in aqueous outflow channel and intraocular pressure (IOP) in a DBA/2J mouse model of pigmentary glaucoma. Design Experimental study. Participants Twenty male DBA/2J mice (40 eyes) aged 9 weeks. Method IOP and anterior segment were monitored regularly. Three mice (6 eyes) were randomly selected at 12, 20, 28 and 36 weeks of age and divided into normal IOP group and high IOP group due to the IOP level. The microstructure of aqueous outflow channel and the distribution of pigment particles between two groups were observed under light microscope. The morphology of pigment particles in the anterior chamber (AC) and trabecular meshwork (TM) was examined by transmission electron microscope, and the diameters of 100 pigment particles were randomly measured by ImageJ software. The diameters of pigment particles in the TM were compared between two groups. Main Outcome Measures IOP, diameter of pigment particles in the AC and TM. Results Progressive pigment liberation, iris stromal atrophy and transillumination defects were found in DBA/2J mice from 20 weeks of age. IOP of DBA/2J mice did not increase at the age of 12 and 20 weeks, and 36.4% and 75% of mice had an increased IOP at 28 and 36 weeks of age, respectively. IOP of mice at different weeks of age was statistically significantly (X２=37.82, P<0.001). Compared with the normal IOP group, the iris in the high IOP group was thinner, with accumulation of pigment-overloaded cells in the AC and on the anterior and posterior iris surfaces, narrowing of anterior chamber angle, and a large amountof pigment particles deposition in TM. The pigment granules in the AC of DBA/2J mice were round in shape with an average diameter of (0.44±0.12 um), or were oval with an average length of (0.77±0.20 um). The diameter of 58.6% round pigment particles and the length of 63.3% oval pigment particles were distributed in 0.40~0.80 um. In normal IOP group, the diameter of 53.3% round pigment particles and the length of 100% oval pigment particles in the TM were >0.40 um. In high IOP group, the diameter of 100% round pigment particles and the length of 100% oval pigment particles length in the TM were >0.40 um. The diameter of round pigment particles (0.58±0.11 um) and the length of oval pigment particles (0.90±0.12 um) in the TM of DBA/2J mice in high IOP group were both greater than those in normal IOP group (0.42±0.12 um, 0.72±0.12 um), and the difference was statistically significant (t=-6.82, -4.657; P<0.001). Conclusion In DBA/2J mice, the maximum permeable diameter in aqueous outflow channel is 0.40 μm. Pigment granules bigger than 0.40 um play the most important role in causing aqueous outflow obstruction and IOP elevation. (Ophthalmol CHN, 2022, 31: 33-38)

Distribution and influencing factors of intraocular pressure in hospital-based myopia teenagers

Hu Di , Jiang Junhong , Zhang Cong , Sun Zheyang , Chen Siping

2022, 31(1):  39-44.  doi:10.13281/j.cnki.issn.1004-4469.2022.01.007

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Objective To investigate distribution and influencing factors of intraocular pressure in hospital-based myopic teenagers. Design Retrospective case series. Participants  973 myopic teenagers (1946 eyes) were enrolled from the Eye Hospital of Wenzhou Medical University from 2011 to 2013. Methods Objective optometry with auto-refractor (Topcon KR-8800), and subjective optometry with a phoropter (Topcon VT-10) were performed. The intraocular pressure (IOP) was measured by noncontact tonometer (Canon TX-F). All subjects was divided into 5-9 years old, 10-14 years old and 15-18 years old groups. Myopic degree based on spherical equivalent refraction (SE) was divided into mild myopia, moderate myopia and high myopia groups. Main Outcome Measures IOP and SE. Results In 973 myopic teenagers, 432 were male (44.40%). Mean SE of two eyes was (-2.42±1.49) D , and mean IOP of two eyes was (17.43±3.02) mmHg (17.52±3.00 mmHg in right eyes and 17.34±3.04 mmHg in left eyes). 10.48% of the left eyes, 10.38% of the right eyes and 14.29% of either eyes had an IOP >21 mmHg. Female had higher IOPs than male (17.69±2.94 mmHg versus 17.30±3.05 mmHg; t=-1.987, P=0.046). IOP decreased gradually with age (5-9 years old 17.29±3.02 mmHg, 10-14 years old 17.59±2.95 mmHg and 15-18 years old 17.81±3.30 mmHg). There was significant correlation between IOP and SE (r=-0.110, P<0.001). The linear function of IOP (Y) with SE (X) was Y=-0.224X+16.972 (F=11.812, P<0.001). Conclusions IOP of hospital-based myopic teenagers increased with age and myopic degree. The IOP in females was higher than that in males. More than 10% of myopic teenager had an IOP greater than 21 mmHg. (Ophthalmol CHN, 2022, 31: 39-44)


Influence of COVID-19 epidemic on the composition of ophthalmic emergency diseases

Qiao Chunyan, Zhang Hui, Li Jian, Wang Qian, Zhang Ju, Hou Fang, Zhang Zheng, Sang Jinghong, Mou Dapeng, Liu Kegao, Cao Kai, You Muxi, Tian Wei, Wei Wenbin, Wang Ningli

2022, 31(1):  45-50.  doi:10.13281/j.cnki.issn.1004-4469.2022.01.008

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Objective To investigate the diseases composition characteristics of ophthalmic emergency in the strict-controlled initial period (January 23, 2020 to February 23, 2020) and the remission period (October 1, 2020 to October 31, 2020) of COVID-19. Design cross-sectional survey. Participants Consecutive 7741 cases of ophthalmic emergency visits in Beijing Tongren Hospital (including Chongwenmen and Yizhuang District branch) during the strict-controlled initial period and remission period of COVID-19. Methods Collect demographic information, emergency diagnosis, and time of visit from the Hospital Information System (HIS) of Beijing Tongren Hospital. Main Outcome Measures Disease composition ratio. Results In 7741 ophthalmic emergency cases, 5704 cases from the remission period were 2.8 times of the initial period. The majority of cases was 30-39 years old (overall 21.8%, initial 22.6%, remission 21.5%). The patient from remission period were younger (initial 43.0±20.1 years, remission 39.6±21.2 years, P<0.001). This was due to a significant increase in the proportion of patients under 18 (initial 12.3%, remission 19.7%, P<0.001). Ocular surface diseases were the most (overall 43.0%, initial 41.4%, remission 43.6%). The others in order were ocular trauma (overall 29.5%, initial 28.9%, remission 29.7%), eyelid and lacrimal disease (overall 10.3%, initial 9.0%, remission 10.9% ), glaucoma (overall 5.8%, initial 7.8%, remission 5.0%, P<0.001), vitreo-retinal diseases (overall 4.0%, initial 4.9%, remission 3.6%), autoimmune disease (overall 3.0%, initial 4.1%, remission 2.6%). Compared with the remission period, electric ophthalmitis (3.5% vs. 0.7%, P< 0.001) and perforating injuries (2.7% vs. 1.7%, P<0.05) were significantly more, and foreign body injury was significantly less (2.7% vs. 6.2%, P<0.05,) in the initial period. Conclusion The outbreak of COVID-19 resulted in a significant decrease in the number of ophthalmic emergency visits. In particular, the visit of children under 18 decreased significantly. Electric ophthalmitis increased, while foreign body injuries reduced during COVID-19 epidemic. (Ophthalmol CHN, 2022, 31: 45-50)

The study on combination of Pentacam and Corvis ST for the diagnosis of forme frusta keratoconus

Zhang Hui , Tian Lei , , Qin Xiao, Guo Lili , Zhang Di , Li Lin, Zhang Haixia

2022, 31(1):  51-56.  doi:10.13281/j.cnki.issn.1004-4469.2022.01.009

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 Objective To explore more combinations of corneal morphology and biomechanics for diagnosisof formefruste keratoconus, so as to explore more potential sensitive parameters. Design Diagnostic test. Participants Fifty patients (50 eyes) with forme frusta keratoconus and 50 patients (50 eyes) with pre-operative corneal refractive surgery were included. Methods  Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic efficiency of formefrustekeratoconus and Delong test was performed. The parameters of area under the ROC curve (AUC) greater than 0.70 were taken as independent variables, and Logistic regression model was established by the forward stepwise method to perform multivariate analysis on the diagnosis of forme fruste keratoconus. Main Outcome Measures Thinnest pachymetry (TP), tomographic and biomechanical index (TBI) and elastic modulus (E). Results Except for Km F, Astig F, Kmax F, A1V, A2T, A2V, HCT, PD, bIOP, there were statistical differences among the other parameters. TP had the highest diagnostic efficiency and AUC was 0.810. The forward stepwise Logistic regression was performed on the parameters with AUC exceeding 0.7, and the resulting model was as follows: CP=eβ/（1+eβ）（β=-0.063×TP-42.158×E+45.919）. The above analysis revealed that TP and E were the independent risk factors for the diagnosis of forme frusta keratoconus. ROC curve analysis showed that the AUC of this model was 0.916, which could significantly improve the diagnostic ability of forme frusta keratoconus (CP vs. TP: Z=2.796, P=0.0052; Delong test). Conclusion There is no significant difference between the diagnostic efficiency of corneal thinnest point thickness and TBI. In the early stage of keratoconus, the total mean curvature in the central 3 mm area of the cornea almost do not change but the difference between the inferior and superior curvature show an increasing trend.The role of corneal elastic modulus in the diagnosis of forme frusta keratoconus is worthy of attention and may be used as a supplementary parameter for disease assessment in the future. (Ophthalmol CHN, 2022, 31: 51-56)

Comparison of visual quality between wavefront-guided and topography-guided FS-LASIK for myopia

Zhang Li , Zhou Yuehua, , Zhai Changbin , Zheng Yan , Zhang Jing

2022, 31(1):  57-62.  doi:10.13281/j.cnki.issn.1004-4469.2022.01.010

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Objective To compare the visual quality between wavefront-guided ablation and topography-guided ablation in femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for myopia. Design Retrospective case series. Participants 130 myopia patients (130 eyes) received FS-LASIK in Beijing Tongren Hospital. Methods 68 myopic patients underwent wavefront-guided customized FS-LASIK (wavefront-guided group) and 62 myopic patients underwent topography-guided FS-LASIK (topography-guided group) were reviewed. Only the right eye data from each patient was analyzed. Visual quality outcomes preoperatively and 6 months postoperatively were compared between groups. Main Outcome Measures Visual acuity, higher order aberrations (HOAs) and contrast sensitivity (CS). Results The uncorrected visual acuity (UCVA) levels after surgery reached or superior to the preoperative best corrected visual acuity (BCVA) were in 94.1% patients in the wavefront-guided group and in 95.2% patients in the topography-guided group 6 months after surgery, respectively (χ2=0.069, P>0.05). There is no significant difference in Log contrast sensitivity (LogCS) values between groups (all P>0.05). There are no significant differences in the amount of changes in the higher order aberrations between the two groups (all P>0.05). Conclusion Both wavefront aberration guided FS-LASIK and corneal topography guided FS-LASIK can obtain good visual acuity and visual quality after surgery. (Ophthalmol CHN, 2022, 31: 57-62)

The suggestion for operative procedures of single band posterior scleral reinforcement for pathologic myopia

Qi Yue, Wang Ningli, Tian Jiaxin

2022, 31(1):  65-68.  doi:10.13281/j.cnki.issn.1004-4469.2022.01.012

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At present, posterior scleral reinforcement is the only effective surgical method to delay axial growth. However, eyes with pathologic myopia have long axial length, thin sclera, and a complex intraocular environment. Besides, the range of the operation is widely and mainly focused on the posterior segment of the eyes. Serious complications may occur due to improper operation. Here, we discussed the indications, contraindications, anesthesia methods, surgical procedures, preoperative and postoperative management, complications, and corresponding approaches of single band posterior scleral reinforcement to establish the standard operative procedure and popularize it effectively. (Ophthalmol CHN, 2022, 31: 65-68)