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Objective To investigate the efficacy of intravitreal injection of Ozurdex® in the treatment of refractory diabetic macular edema (DME) with different optical coherence tomography (OCT) patterns. Methods A total of 38 patients (41 eyes) who underwent fundus examination and were diagnosed with refractory DME in Department of Ophthalmology in our hospital from June 2018 to June 2020 were enrolled in this study, and according to the OCT pattern, they were divided into diffuse retinal thickening (DRT) group, cystoid macular edema (CME) group, and serous retinal detachment (SRD) group. Intravitreal injection of Ozurdex® was performed for all diseased eyes as needed, and best corrected visual acuity (BCVA) and OCT measurements were performed before treatment and at 1, 3, and 6 months after treatment. The three groups were compared in terms of BCVA, central foveal thickness (CFT), the integrity of external limiting membrane, ellipsoid zone integrity, and the number of hyperreflective dots (HRDs) before and after treatment. Results All three groups had a significant improvement in BCVA at 1, 3, and 6 months after treatment (Fintra-group=15.334-42.187,P0.05), and at 1, 3, and 6 months after treatment, there was a significant change in the proportion of diseased eyes with different numbers of HRDs (H=23.645-39.117,P

OBJECTIVE: To probe into the protective effect and mechanism of intravitreal injection of avastin on retinal damage in mice with age-related macular degeneration ( AMD). METHODS: Forty C57BL/6 mice were randomly divided into the control group, model group, avastin low-dose group and avastin high-dose group, with 10 cases in each group. Except for the control group, the other three groups of mice were injected with sodium iodate (NaIO3) through the tail vein to induce the establishment of AMD models. Avastin low-dose and high-dose groups were given intravitreal injections of 15 mg/ mL and 20 mg/ mL avastin, the control group and model group were injected with the same amount of PBS solution. Fourteen days later, the four groups of mice were all photographed fundus images, frequency domain optical coherence tomography (SD-OCT) was used to detect the thickness of the retina, fundus fluorescein angiography (FFA) was performed, and the electroretinogram was recorded. The four groups of mice were taken blood from the eye vein to detect superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, malondialdehyde (MDA), reactive oxygen species (ROS). Hematoxylin-eosin (HE) staining was used to observe retinal morphology changes, TUNEL staining was used to detect retinal cell apoptosis, immunofluorescence staining was used to detect the expression of LC3 in retina, Western blotting was used to determine the expression of autophagy-related proteins in retina. RESULTS: Compared with the model group, the avastin lowdose and high-dose groups had reduced fundus deposits, increased retinal thickness, and decreased vascular leakage. There were significant differences in the amplitudes of a and b waves between the control group, model group, avastin low-dose group and avastin high-dose group (F was 398. 521 and 501. 247 respectively, P<0. 05). Compared with the model group, the a-wave and b-wave amplitudes in the avastin low-dose group and avastin high-dose increased, with statistically significant differences (P<0. 05). There were significant differences in activities of serum SOD, GSH-Px, CAT, contents of MDA, ROS and positive rate of TUNEL among the control group, model group, avastin low-dose group and avastin high-dose group ( F was 302. 547, 655. 259, 218. 954, 260. 135, 1 452. 098 and 328. 193 respectively, P <0. 05). Compared with the model group, the activities of serum SOD, GSH-Px and CAT in the avastin low-dose group and avastin high-dose group increased, while the contents of MDA and ROS decreased, the positive rate of TUNEL decreased, with statistically significant differences ( P < 0. 05). There were significant differences in p62, Beclin-1 protein expression and LC3-II/ LC3-I ratio among the control group, model group, avastin low-dose group and avastin high-dose group (F was 56. 259, 105. 890 and 78. 314 respectively, P<0. 05). Compared with the model group, the fluorescence expression of LC3 in retina of avastin low-dose group and avastin high-dose group was enhanced, the expression of p62 protein was down-regulated, and the protein expression of Beclin-1 and the ratio of LC3-II/ LC3-I were up-regulated, with statistically significant differences ( P < 0. 05). CONCLUSIONS: Intravitreal injection of avastin can protect the retina of AMD mice induced by NaIO3, and its mechanism may be related to the promotion of autophagy. [ABSTRACT FROM AUTHOR]

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Neovascular retinal diseases pose a significant burden, often resulting in visual impairment. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs serves as the primary therapeutic approach. Nonetheless, certain patients necessitate continued anti-VEGF treatment post-vitrectomy or other ocular surgeries. Emerging evidence suggests that variations in surgical techniques and postoperative vitreous cavity management may induce distinct intraocular pharmacokinetics (PK) of anti-VEGF agents following vitrectomy, prompting potential adjustments in therapeutic strategies. This review offers a thorough examination of the pharmacokinetic determinants impacting anti-VEGF drugs and their intraocular dynamics post-vitrectomy.

Objective: To study the clinical efficacy of anti-VEGF antibody in the vitreous cavity for treatment of diabetic macular edema under different optical coherence tomography (OCT) classifications. Methods: A selection of 60 patients with diabetic macular edema who were treated in our hospital from January 2019 to March 2021 were divided into diffuse macular edema (DRT) group, cystoid macular edema (cME) group and serous retina based on OCT detection Disengagement (SRD) group, 20 cases in each group. All patients received intravitreal injection of anti-VEGF antibody treatment. The three groups of patients were compared with clinical treatment efficacy, macular edema morphology, best corrected vision acuity (BCVA), central macular thickness(CMT) and the incidence of adverse reactions. Results: (1) The effective rates of clinical treatment in the DRT, CME and SRD groups were 85.0 %, 75.0 %, and 50.0 %, respectively, and the regression rates of macular edema post-treatment were 55.0%, 25.0%, and 10.0%, respectively, and the differences between the groups were significant (P<0.05); (2) There was no difference in BCVA and CMT of the three groups of patients pretherapy (P>0.05), and the BCVA and CMT of the three groups of patients were reduced post-treatment (P<0.05), and the DRT and CME groups post-treatment The BCVA and CMT of patients were lower than those in the SRD group (P<0.05); (3) The incidence of adverse reactions during treatment in DRT, CME and SRD groups was 10.0 %, 10.0 % and 25.0 %, respectively, but there was no difference in the incidence of adverse reactions during treatment in the three groups(P>0.05). Conclusion: Different OCT types of diabetic macular edema have different clinical effects after vitreous anti-VEGF antibody treatment. Among them, DRT patients have the best clinical treatment effect, while SRD patients have the worst effect. [ABSTRACT FROM AUTHOR]

Objective: To research the clinical effect of intravitreal injection of Conbercept in the prevention of proliferative vitreoretinopathy after vitrectomy for severe posterior scleral laceration. Methods: From September 2018 to September 2020, 40 cases of patients (40 eyes) with severe posterior scleral laceration in our hospital were selected for the study, and they were randomly divided into the control group 20 eyes (treated with conventional scleral laceration suture and pars plana vitrectomy) and the observation group 20 eyes (treated with scleral laceration suture and pars plana vitrectomy combined with intravitreal injection) of Conbercept). The visual acuity and intraocular pressure were compared between the two groups before and after treatment,and the incidence of proliferative vitreoretinopathy and retinal redetachment were compared between the two groups after treatment. Results: After treatment, the best corrected visual acuity was significantly higher than that before treatment in both groups, and the intraocular pressure was normal in two groups.The The incidence of proliferative vitreoretinopathy in the observation group (15.0 %) was significantly lower than that in the control group (45.0 %, P<0.05), and the recurrence rate of retinal detachment in the observation group (5.0 %) was lower than that in the control group (30.0 %, P>0.05). Conclusions: Vitrectomy combined with intravitreal injection of Conbercept for severe posterior scleral laceration can effectively reduce the incidence of proliferative vitreoretinopathy and the recurrence rate of postoperative retinal detachment,and improve the visual prognosis of patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). Methods: This was a prospective randomized controlled study. Patients diagnosed with DME in the Ophthalmology Department of Beijing Hospital were enrolled from January 2020 to December 2022. Patients were randomized in a ratio of 1∶1 using a table of random numbers into the ranibizumab monotherapy group and the SMPL combined with ranibizumab therapy group. We compared the changes of best-corrected visual acuity, central macular thickness measured by optical coherence tomography and optical coherence tomography angiography parameters, including the vessel density of the superficial and deep capillary plexus (DCP), foveal avascular zone size and peripapillary vessel density, at baseline, 6 and 12 months after the treatment. After 12 months of follow-up, fundus fluorescein angiography results, adverse events, and the number of injections or laser therapies were recorded. The Fisher's exact test and group t -test were used for statistical analysis. Results: Seventy-two patients (72 eyes) were enrolled, with a mean age of (61.1±8.2) years. Patients in the combination therapy group included 19 males and 17 females, while patients in the ranibizumab monotherapy group were 17 males and 19 females. There was no statistically significant difference in baseline characteristics between the two groups ( P >0.05). A significant improvement in best-corrected visual acuity was shown in both groups at 6 and 12 months [(58.5±12.9) and (58.2±12.2) ETDRS letters in the combination therapy group, and (63.3±13.1) and (63.8±12.5) ETDRS letters in the ranibizumab monotherapy group]. A significant reduction in central macular thickness was shown in both groups at 6 and 12 months [(451.0±185.5) and (380.4±159.3)μm in the combination therapy group, and (387.5±135.5) and (372.8±146.1)μm in the ranibizumab monotherapy group]. However, there was no significant difference between groups at each timepoint (all P >0.05). At 12 months, the vessel density of the superficial capillary plexus showed no statistical difference compared to the baseline value in each group or between groups (42.6%±5.9% in the ranibizumab monotherapy group and 42.2%±5.5% in the combination therapy group, P >0.05). The vessel density of the DCP in the combination therapy group significantly increased to 47.5%±5.6% at 12 months, significantly different from that in the ranibizumab group (43.4%±5.1%; P <0.05). The foveal avascular zone size in the ranibizumab monotherapy group reduced to (0.32±0.13) mm 2 , significantly different from that in the combination therapy group [(0.34±0.16) mm 2 ] at 12 months ( P <0.05). Patients in the ranibizumab monotherapy group received (7.3±2.5) intravitreal injections, while patients in the combination therapy group received 3 injections. No unfavorable outcomes on fundus fluorescein angiography or systemic or topical severe adverse events were observed during the follow-up. Conclusions: The SMPL combined with intravitreal ranibizumab injections was effective and safe in treating DME patients. The combination treatment significantly reduced the number of injections and improved the vessel density of the DCP and macular ischemia, compared to the ranibizumab monotherapy.

Objective To compare and analyze the changes of cytomegalovirus (CMV)-DNA load and CD4+ T lymphocyte count in blood, aqueous humor and vitreous humor of patients with acquired immunodefficiency syndrome (AIDS) complicated with cytomegalovirus retinitis (CMVR) before and after intravitreal injection of ganciclovir combined with systemic antiviral therapy. Methods Seven patients (thirteen eyes) with AIDS complicated with CMVR admitted to the First Affiliated Hospital of Guangxi Medical University from January 2016 to January 2018 were selected. All patients were given systemic ganciclovir and foscarnet sodium antiviral therapy combined with intra-ball injection of ganciclovir (800 mg/0. 08 mL, once a week,2 —5 times in total). The CMV-DNA load in blood, aqueous humor and vitreous humor, CD4+ T lymphocyte count in blood, visual acuity and fundus changes multiple times before and after the injections were collected. Results The mean Log MAR best corrected visual acuity of seven patients (thirteen eyes) before operation was 1.07± 0. 83 and that of the post-operation was 0. 71 ± 0. 83. The difference was statistically significant (t = 4. 287, P=0.001). The fundus of all patients showed central CMVR. The number of cases with damage of fundus lesions were reduced to six patients compared with that of pretherapy, and the difference was statistically significant (H=6. 072,P = 0. 013). There was no significant difference in blood CMV-DNA load before and after the injection (Z = —1. 461, P = 0. 281). The CMV-DNA load in the vitreous humor before the injection was 7. 00 X 106 copy/mL and that of the last post-injection was 9. 25 X106 copy/mL. The CMV-DNA load in vitreous humor after the last injection was lower than that of the pre-injection, and the difference was statistically significant (Z = —2. 589,P =0. 027). The CMV-DNA load in the aqueous humor before injection was 4. 20 X 105 copy/mL and that of the last post-injection was 1. 94 X 104 copy/mL. The CMV-DNA load in the aqueous humor after the last injection was lower than that of the pre-injection, the difference was statistically significant (Z= —2. 312,P =0. 031). The CDC T lymphocyte count of the five patients (nine eyes) was less than 50 μL-1 before the injection, accounting for 71. 43%, while there were four patients (eight eyes) who got the count of more than 50 μL-1 after the last injection, accounting for 57. 14%. Among the seven patients ( thirteen eyes), the number of those whose CMV-DNA load of the vitreous fluid and the aqueous humor increase by one patient rather than decrease. Three patients (five eyes) showed a consistent increase of CMV-DNA load in blood, vitreous fluid and aqueous humor before injection. Before injection, the CMV-DNA load in blood of four patients( six eyes) was negative, while the CMV-DNA load in vitreous humor and aqueous humor was positive (9. 30 X 10³ — 4. 30 X 108 copy/mL), which was significantly higher than that of the normal level. Conclusion The aqueous humor and vitreous fluid examination could be used to diagnose and predict the occurrence and development of CMVR. After the highly effective antiretroviral therapy, some patients still had the high concentration of CMV-DNA in the aqueous humor and vitreous humor even though their blood CMV-DNA load was negative. There was a higher consistency of blood-aqueous humor-vitreous fluid CMV-DNA load in the AIDS patients with the first-episode of CMVR. [ABSTRACT FROM AUTHOR]

A 36-year-old male patient presented with a decrease in vision after undergoing scleral suturing for a left eye injury caused by an iron hook, combined with intravitreal injection of cefuroxime. Ocular examination revealed extensive gray-white edematous areas in the macular region, along with focal serous shallow retinal detachment in the posterior pole. Following admission, comprehensive ophthalmic examinations were conducted, leading to the diagnosis of toxic retinal damage in the left eye. Treatment with oral corticosteroids and interventions to improve microcirculation were initiated, resulting in improved visual acuity. At the six-month follow-up, the patient's visual acuity had recovered to 0.5.

Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness in the elderly, and anti-vascular endothelial growth factor (VEGF) therapy is currently the primary treatment approach. However, the real-world effectiveness of nAMD treatment is not always satisfactory and faces various challenges. Frequent administration and follow-up burdens can lead to decreased patient compliance during long-term treatment, resulting in suboptimal outcomes. Some lesions exhibit poor or no response to anti-VEGF treatment, leading to difficulties in maintaining or even declining visual acuity. Factors such as lesion fibrosis and tissue atrophy can contribute to visual deterioration. Therefore, standardizing and individualizing treatment plans, along with enhancing comprehensive monitoring and management throughout the disease course, are crucial improvement measures. The evidence-based guidelines for diagnosis and treatment of age-related macular degeneration in China, released in 2023, provide guidance for standardized clinical diagnosis and treatment. Meanwhile, research and development of new drugs and administration methods are anticipated for the future.

A 61-year-old male patient presented with blurred vision in the right eye for 1 day. The patient had previously undergone phacoemulsification with intraocular lens implantation (10 years ago) and intravitreal implantation of dexamethasone (due to uveitis) in the eye. There was edema in the inferior cornea, along with Descemet membrane folds. The rod-shaped dexamethasone implant was visible in the inferior anterior chamber. Without pupil dilation, the patient was asked to keep a supine position and avoid head tilting for 1 day. The implant spontaneously relocated into the vitreous cavity, resulting in a reduction of corneal edema. This suggests that the dislocation of the intravitreal implant into the anterior chamber may be caused by a local zonular abnormality, and the dislocated implant has the potential to reposition itself spontaneously.

Objective: To investigate the ffect of intravitreal injection of razumab on clinical efficacy and retinal function development in retinopathy of prematurity(ROP). Methods: 80 cases of ROP were enrolled in our hospital from June 2014 to June 2018,who were randomly divided into control group and observation group with 40 cases in each group.The control group were treated by laser, while the observation group were treated by intravitreal injection of razumab. The curative effect and recurrence of the two groups were compared after treatment and the development of retinal function was examined by flash electroretinogram(F-ERG) after 6 months of follow-up. Results: After treatment, the disease control rate in the observation group were significantly higher than that in the control group, and the disease progression rate and recurrence rate were significantly lower than those in the control group(P<0.05). The results of F-ERG examination showed that the response amplitude of rod cell system in the control group were significantly lower than that in the observation group, the latency were significantly longer than that in the observation group, and the maximum mixed response a and b wave amplitude were significantly lower than that in the observation group(P<0.05). There was no significant difference in amplitude ratio b/a and latency between the two groups(P>0.05), and also no significant difference in the latency of a wave and the amplitude of a and b wave of cone cell response between the two groups(P>0.05). The latency of b wave of cone cell response in the control group were significantly longer than that in the observation group, and the Oscillatory potentials(Ops) were significantly lower than that in the observation group(P<0.05). Conclusion: Intravitreal injection of razumab is effective, simple and rapid in the treatment of children with ROP, and the development of retinal function tends to be more normal than that of laser therapy, which is suitable for children with ROP. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and safety of intravitreal dexamethasone implant (IDI) in diabetic macular edema (DME) patients with and without prior vitrectomy. Methods: A retrospective cohort study was conducted on DME patients who received IDI treatment at the Aier Eye Hospital, Beijing from March 2018 to August 2020. Patients were divided into two groups according to whether they had undergone vitrectomy or not. Clinical and follow-up data, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), occurrence of ocular and systemic complications, and time to DME recurrence and retreatment, were collected before and after IDI injection at 15 days, 1, 2, 3, and 6 months. Statistical analyses were performed using t -test, Mann-Whitney U -test, χ 2 test or Fisher's exact test, and generalized estimating equations. Results: Thirty-six patients (41 eyes) were included, with 19 patients (21 eyes) in the vitrectomy group and 17 patients (20 eyes) in the non-vitrectomy group. Compared with baseline, BCVA of eyes in the vitrectomy group was significantly improved at 15 days after IDI injection, with values of 1.00 (0.52, 1.31) and 0.61 (0.30, 1.00), respectively ( Z =-2.10, P =0.036); BCVA of eyes in the non-vitrectomy group was significantly improved at 1 month after IDI injection, with values of 0.76 (0.60, 1.35) and 0.52 (0.10, 0.70), respectively ( Z =-2.24, P =0.025). Compared with baseline, CMT of eyes in both groups was significantly reduced at all follow-up time points after 15 days of IDI injection (all P <0.05). In the vitrectomy group, CMT before and 15 days after injection were 487 (438, 661) μm and 389 (340, 553) μm, respectively ( Z =-3.45, P <0.001); in the non-vitrectomy group, CMT before and 15 days after injection were 486 (410, 641) μm and 323 (290, 396) μm, respectively ( Z =-4.07, P <0.001). There were no statistically significant differences in BCVA and CMT between the two groups at all follow-up time points (all P >0.05). The time to DME recurrence was 3.0 (3.0, 4.0) months in the vitrectomy group and 5.0 (4.0, 5.0) months in the non-vitrectomy group, with no significant difference between the two groups ( P =0.675). Four eyes (19.0%) in the vitrectomy group and three eyes (15.0%) in the non-vitrectomy group had high IOP, with no significant difference ( P =0.529). No severe ocular or systemic complications were observed in any patients. Conclusions: IDI treatment is safe and effective in DME patients with and without prior vitrectomy, with similar efficacy, but with faster onset of action in patients with prior vitrectomy. There was no significant difference in DME recurrence within 6 months after IDI injection between the two groups.

Objective: To compare different types of diabetic macular edema (DME) classified based on optical coherence tomography (OCT) for their responses to Conbercept injection and analyze the factors that affect the treatment responses., Methods: We retrospectively analyzed the clinical data of 65 patients (76 eyes) with DME diagnosed and treated with intravitreal injection of Conbercept (1+PRN) in our hospital from February, 2019 to February, 2021. According to OCT findings, DME in these patients was classified into cystic macular edema (CME; 28 eyes), serous retinal detachment (SRD; 33 eyes), and diffuse retinal thickening (DRT; 15 eyes). The best corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before and at 3 months after the first treatment. The baseline OCT characteristics of different types of DME were compared, and the correlation of these OCT characteristics with the treatment response to Conbercept was analyzed., Results: All the patients showed significant improvement of the BCVA 3 months after the treatment ( P < 0.05). For all the 3 types of DME, the CRT at 3 months after the first treatment was significantly reduced as compared to the baseline ( P < 0.05). The number of hyperreflective foci (HF) in the outer retina and the proportion of ellipsoid zone (EZ) interruption were the greatest in SRD group ( P < 0.05). The baseline outer retinal HF was significantly correlated with the baseline CRT, CRT changes and CRT after treatment (all P < 0.05). The patients with baseline outer limiting membrane (ELM)/ EZ disruption had poorer baseline BCVA, greater baseline CRT, greater variation of CRT and poorer BCVA at 3 months after treatment (all P < 0.05)., Conclusion: For all the 3 types of DME, treatment with intravitreal injection of Conbercept can significantly improve the BCVA and CRT of the patients. DME of the SRD type has the best morphological response to Conbercept, while the DRT type has a relatively poor response. A greater number of HF at baseline may indicate a better morphological response to Conbercept treatment, and baseline ELM/EZ disruption may suggest a poor visual prognosis at 3 months after treatment.

Diabetic retinopathy(DR)is the major microvascular disease in diabetic patients,and it is also one of the main blinding eye diseases in the current population.The typical pathological change of DR in the eyes is vascular endothelial growth factor(VEGF)-mediated neovascularization induced by retinal ischemic stimulation.Therefore,anti-VEGF drugs have gradually become one of the mainstream methods to treat DR and DR-induced diseases such as diabetic macular edema.Recent studies have proved that anti-VEGF drugs have certain effects on ocular blood vessels and blood flow in patients with DR,while the specific mechanism has not been fully elucidated.This article summarizes the research progress on the effects of intravitreal injection of anti-VEGF drugs on the ocular blood vessels and blood flow in patients with DR.

Objective: To elevated the retinal toxicity of intravitreal ganciclovir in albino rabbit eyes. Methods: Experimental study. Twenty-four New Zealand albino rabbits (forty-eight eyes) were divided into four groups by random. Three groups were prepared for ganciclovir experiment, named A, B, C. Each group received intravitreal injection ganciclovir dose at 400 μg/0.05 ml, 2 mg/0.05 ml and 5 mg/0.05 ml respectively. The other group named D served as a control accepted intravitreal injection 0.9% normal saline 0.1 ml. Before and after 1, 2 and 4 weeks, flicker full field electroretina gram (ERG) was recorded. After 1, 2 and 4 weeks light and electron microscopic tests were recorded for further toxicity study. Results: There was significant difference in amplitude of maximal combined response a wave in one week(χ(2)=8.319, P= 0.04), and pairwise comparison the 5 mg group (140.50 μV) was significantly lower than the control group (165.00 μV) (χ(2)=-2.830, P= 0.028). Maximal combined response b wave in four weeks(χ(2)=-10.626, P= 0.014), and pairwise comparison the 5 mg group (261.50 μV) was significantly lower than the control group (398.00 μV) (χ(2)=-2.973, P= 0.018). 30 Hz flicker response in one, two and four weeks(χ(2)=17.589, 8.225, 8.997, P= 0.001, 0.042, 0.02), and pairwise comparison the 5 mg group (71.3μV, 106.00μV, 63.60μV) was significantly lower than the control group (118.50μV, 129.00μV, 116.50μV) (χ(2)=-4.142, -2.826, -2.713, P= 0.000, 0.028, 0.040). There was no histologic retinal toxicity evidence of group 400 μg and control group observed by light microscopy in any stage of the study. Histologic changes of group 2 mg four week later, group 5 mg two and four week later include inner nuclear layer loose arranged, nuclear of ganglia were widened and outer plexiform layer stained less in four week later. By electron microscopic observation, the ultrastructure of retina changed to different degrees and became worse in each experimental group with significant mitochondrial swelling and hydropic changes were seen in the inner segments of photoreceptors, loosely arranged and disordered in the outer segment of photoreceptors four weeks later. Conclusions: The retinal function and morphology were normal in group 400 μg. Group 2 mg and 5 mg had retinal toxicity, and 5 mg was more severe. Therefore, the clinical application of ganciclovir in the treatment of acute retinal necrosis (ARN) should select the minimum effective dose to avoid the occurrence of retinal toxicity. (Chin J Ophthalmol, 2020, 56:279-285) .

Pathological myopia refers to high myopia with fundus pathological changes. Choroidal neovascularization is one of its serious complications, and also the main cause of visual loss. Currently, the first-line treatment is anti-VEGF treatment, with good efficacy, high safety, good prognosis, and other advantages of vision. Commonly used anti-VEGF drugs include bevacizumab, ranibizumab, aflibercept, and conbercept. The main treatment strategies include 1+pro re nata and 3+pro re nata, and the standard of REPAIR test is often used to evaluate the re-injection. This article reviews the advantages of anti-VEGF therapy, drug selection, treatment strategy, and re-injection criteria. (Chin J Ophthalmol, 2019, 55:791 - 795) .

The response to anti-vascular endothelial growth factor (VEGF) treatment is variable. It is generally measured in terms of changes in correlated functional and/or anatomical outcomes, and patients are then classified as optimal response, poor response and non-response. The precise cause of non-response remains undetermined. A variety of factors could account for poor or non-response to anti-VEGF therapy, such as age, baseline vision, disease course, lesion characteristics and genomic polymorphism. At the present time, many studies on the genetic factors of non-response or poor response to anti-VEGF treatment mainly focus on VEGF genes (VEGF-A, VEGFR-2), complement factor H (CFH), age-related maculopathy susceptibility 2 (LOC387715/ARMS2), high temperature factor A-1 (HTRA1), interleukin-related gene (IL-8 rs4073) and so forth. It is still worthy of further investigations that how to assess genetic reasons for non-response or poor response, so that we can provide individualized treatment sequences and predict the response to anti-VEGF therapy. (Chin J Ophthalmol, 2018, 54:873 - 878) .

Objective: To compare the clinical efficacy of treating different diseases with the same acupuncture comprehensive therapy and intramuscular injection of ranibizumab in the treatment of macular edema, and to explore an effective treatment., Methods: A retrospective study was conducted, ①Acupuncture combined with EA at Xinming one (Extra), Sizhukong (TE 23), Tongziliao (GB 1), once every other day; ②acupoint injection, alternation with compound anisodine and mecobalamine injection at Qiuhou (EX-HN 7), Taiyang (EX-HN 5), once every other day; ③auricular acupressure at yan (LO 5 ), gan (CO 12 ), shen (CO 10 ) and other points; ④plum-blossom needle at Zhengguang 1 (Extra), Zhengguang 2 (Extra), once every other day were given in the acupuncture group (20 cases, 24 affected eyes). Intramuscular injection of 0.5 mg ranibizumab was given in the ranibizumab group (22 cases, 23 affected eyes). The macular foveal thickness, early treatment diabetic retinopathy study of (ETDRS) visual acuity chart, self-evaluation scores of visual function impairment ophthalmopathy patient's quality of life scale were observed before treatment, after 3, 6, 9 and 12 months of treatment, and the clinical efficacy was evaluated., Results: ①At all the observation time points of the treatment, the macular thickness was lower than that before treatment in the two groups (all P <0.05), and there was no significant difference between the acupuncture group and the ranibizumab group (all P >0.05). ②Visual acuity was higher than that before treatment at all the time points in the two groups (all P <0.05). After 3-months treatment, there was no statistical significance between the two groups ( P >0.05). After 6, 9, and 12 months treatment, the visual acuity in the acupuncture group was better than that in the ranibizumab group ( P <0.05, P <0.01). ③At all the time points, the quality of life scores were lower than those before treatment in the two groups (all P <0.05). There was no statistical significance in the ranibizumab group compared with those before treatment (all P >0.05). In 3, 6, 9 and 12 months of treatment, the quality of life scores in the acupuncture group was better than those in the ranibizumab group ( P <0.05, P <0.01). ④The total effective rate of the acupuncture group was 79.2% (19/24), which was better than 30.4% (7/23) in the ranibizumab group ( P <0.05). ⑤The improvement of visual acuity before and after treatment was negatively correlated with the course of disease ( P <0.05), ie, the longer the disease course of the eyes, the worse the visual acuity and the worse the effect., Conclusion: Acupuncture comprehensive treatment can effectively treat macular edema, significantly improve the patient's vision, improve the subjective experience and the quality of life, and the shorter the course of the disease the more significant effect. Acupuncture comprehensive treatment is better than intramuscular injection of ranibizumab.

Objective: To evaluate the efficacy of vitrectomy and etiological diagnosis in the treatment of fungal endophthalmitis. Methods: A retrospective survey was done on the clinical manifestation, etiological diagnosis and treatment efficacy of 15 patients (15 eyes) who had been diagnosed with fungal endophthalmitis at the inpatient department of Peking Union Medical College Hospital during 2002-2015. A total of 15 eyes of 15 patients, 3 male and 12 female patients, were included in this study. The mean age of the patients was (45.8±15.3) years. Among the 15 eyes, 12 (12 patients) were diagnosed with endogenous fungal endophthalmitis and 3 (3 patients) were diagnosed with exogenous fungal endophthalmitis. Fourteen eyes have been misdiagnosed with uveitis, systematic or local application of glucocorticoid and/or immunosuppressor have been conducted on the patients which resulted in exacerbation. Baseline visual acuity: light perception in 2 eyes, hand movement for 12 eyes, and 1 eye of 0.1. Six eyes showed slight inflammatory reaction in anterior chamber, four eyes showed moderate inflammatory reaction in anterior chamber, while five eyes showed severe inflammatory reaction with hypopyon in anterior chamber. B-Scan ultrasound examination showed inflammatory vitreous opacity in all 15 eyes, combined proliferative vitreoretinopathy (PVR) were found in 11 eyes, retinal detachment were found in 10 eyes, which include 6 cases of tractional retinal detachment, 1 case of exudative retinal detachment, and 3 cases of retinal and choroid detachment. Forty eyes underwent vitrectomy, 1 eye underwent intravitreal injection. Nine eyes were processed with silicone oil tamponade, one eye was processed with C(3)F(8) tamponade. At the beginning of the operation, vitreous fluids were collected for preparing smears which were later used for fungus culture and drug susceptibility testing. Results: According to the smear results of vitreous fluid, fungal hyphae and spores were found in 10 eyes. The fungus culture indicated positive results in 12 eyes, including candida albicans in 6 eyes, fusarium, candida parapsilosis, paecilomyces lilacinus, asoergullus terreus, mulan candida and aspergillus in 1 eye respectively. Based on etiological diagnosis, 14 eyes received amphotericin B intraocular injection during operation, and 9 patients received fluconazole (venous transfusion or oral administration), 2 patients received voriconazole through venous transfusion or oral administration, one patient received itraconazole through oral administration. All 15 eyes received local application of amphotericin B eyedrop or fluconazole eyedrop. The intraocular inflammations in all 15 eyes were mitigated. The visual acuity improved in 6 eyes, remained unchanged in 4 eyes, and reduced in 5 eyes. Postoperative visual acuity achieved 0.1 to 0.15 in 2 eyes, 0.01 to 0.04 in 2 eyes, CF in 2 eyes, HM in 4 eyes, LP in 2 eyes, and NLP in 3 eyes. The retina of 5 eyes remained in position, the retina of 2 eyes reattached, the retina of 2 eyes failed to reattach. Recurrent retinal detachment happened in the other 6 eyes, 5 of which received reoperation. Eventually, the retina of 10 eyes reattached, and the retina of the 5 eyes failed to reattach. Conclusions: Vitrectomy is an effective method for treatment of fungal endophthalmitis. The positive rates of vitreous smear and fungus culture were really high. Application of sensitive anti-fungal drugs based on etiological diagnose can improve therapeutic level. (Chin J Ophthalmol, 2018, 54: 270-276) .

Objective: We report a case of an 18-year-old woman with systemic antibiotic anaphylaxis who presented anasarca and bilateral visual loss two weeks after the intravenous use of pazufloxacin. Ancillary fundus tests revealed bilateral cotton-wool spots, Purtscher flecken, edema, and retinal arteriolar occlusion around the optic disc. After pulse corticosteroid, administration of anti-anaphylactic agent, and general support therapy for one month, the patient showed a favorable change, with the symptoms lessened or free systemically, except the continuous aggravation of fundus ischemic change. After two intravitreal injections of Ranibizumab, there were still a large area of capillary non-perfusion and neovacularizations in the binocular retina, resulting in vitreous hemorrhage. The patient's visual acuity had still light perception after right-eye vitrectomy and presented no improvement during the postoperative follow-up of two years. Literature review revealed that there were many causes associated with Purtscher-like retinopathy, and the consequent visual impairment varied significantly. Prompt management of the underlying condition is crucial in giving the patient the best chance to restore vision.

Ocular drug delivery by conventional routes of administration cannot reach or maintain therapeutic drug concentrations in the target tissues for a long duration due to the presence of various anatomical and physiological barriers. Treatment of chronic ocular diseases especially posterior segment of ocular diseases requires novel drug delivery systems that is capable overcome these barriers for efficacious delivery. In recent years, the ocular sustained-release drug delivery system, as a new drug delivery approach, has drawn tremendous attention for its advantages of improving local drug concentration, prolonging action time and reducing frequency of injection. Researchers have been devoted to the developing more effective sustained-release drug delivery systems in order to achieve better clinical efficacy. This article discusses various current sustained-release corticosteroids delivery systems. (Chin J Ophthalmol, 2018, 54: 154-160) .

Diabetic macular edema (DME), which is the consequence of the failed blood-retinal barrier, has become a leading cause of blindness in diabetic patients. Vascular endothelial growth factors (VEGF) and a series of inflammatory factors participate in the pathophysiology of DME. Laser photocoagulation was accepted as the first-line therapy before anti-VEGF therapy was proved to be more effective by several clinical trials. Anti-VEGF therapy has been regarded as the standard treatment, but there are still lots of cases resistant to anti-VEGF therapy. Corticosteroid treatment has also been proved effective, especially in refractory DME. This demonstrates that inflammation plays a role in DME as well. Here we discuss the situation of anti-VEGF and anti-inflammation therapies for DME. (Chin J Ophthalmol, 2017, 53: 724-728) .

Retinoblastoma (RB) is the most common intraocular malignancy in childhood. It may seriously affect vision, and even threaten the life. The early diagnosis rate of RB in China remains low, and the majority of patients are at late phase with high rates of enucleation and mortality. The International Intraocular Retinoblastoma Classification and TNM staging system are guidances for therapeutic choices and bases for prognosis evaluation. Based on the sequential multi-method treatment modality, chemotherapy combined with local therapy is the mainstream in dealing with RB, which may maximize the results of eye saving and even vision retaining. New therapeutic techniques including supra-selective ophthalmic artery interventional chemotherapy and intravitreal chemotherapy can further improve the efficacy of treatment, especially the eye salvage rate. The overall level of RB treatment should be improved by promoting the international staging, new therapeutic techniques, and the sequential multiple modality treatment. (Chin J Ophthalmol, 2017, 53: 561 - 565) .

Objective: To evaluate the efficacy and safety of intravitreal chemotherapy for refractory vitreous seeding from retinoblastoma. Methods: Retrospective series of case studies. Nine patients (13 eyes) with the diagnosis of refractory vitreous seeding were enrolled in Department of Ophthalmology of Eye& ENT Hospital of Fudan University from March 2014 to October 2015.There were 6 males and 3 females. Children aged 8 to 40 months, median age of 18 months. In the 13 eyes, 3 eyes were E period, 9 eyes were D period, and 1 eyes were C period. The fundus was examined by indirect ophthalmoscope and recorded by RetcamIII. Systemic chemotherapy was performed using the VEC protocol, that is vincristine, etoposide, and carboplatin. Local treatment also involves cryotherapy and/or thermotherapy. All patients were treated with intravitreal injection of melphalan. They underwent intravitreal melphalan, once every 4 weeks, with an average of 3 times of injections. The treatment dose of melphalan is 20 to 40 μg per dose. Observe the vitreous seed control and complications of therapy. Results: Vitreous seeds control was attained in all cases. There was no case of orbital extension or remote metastasis. Complications included retinal pigment epithelial and choroidal atrophy in 7 eyes, pupillary synechia and iris atrophy in 2 eyes,retinal vasculitis and vascular occlusion in 2 eyes, optic atrophy in 2 eyes, vitreous hemorrhage in 1 eye, and temporary hypotony in 3 eyes. Conclusions: Intravitreal melphalan is an effective treatment for refractory vitreous seeding from retinoblastoma. High dose may lead to local adverse reactions. ( Chin J Ophthalmol , 2017 , 53 : 570-574).

Objective: To investigate the effect of pigment epithelial-derived factor (PEDF) gene-modified human umbilical cord mesenchymal stem cells (MSC) on rats with diabetic retinopathy (DR). Methods: Experimental study. Human umbilical cord MSC were transfected by lentivirus packaging PEDF-MSC-green fluorescent protein (GFP) and GFP-MSC plasmid vectors, and the expression of PEDF and vascular endothelial growth factor (VEGF) was measured in the cell culture medium. Fifty adult male Sprague-Dawley rats were randomly divided into five groups: normal control group (group A), DR control group (group B), phosphate-buffered saline (PBS) treated group (group C), GFP-MSC treated group (group D) and PEDF-MSC-GFP treated group (group E), with 10 rats in each group. Streptozotocin was intraperitoneally injected to make early DR models. After four-month intervention, groups D and E were given intravitreal injection of GFP-MSC and PEDF-MSC-GFP; group C was given intravitreal injection of phosphate-buffered saline; groups A and B did not receive special treatment. The changes of retina in different groups were detected by hematoxylin and eosin staining, and the thickness of inner plexiform layer, inner nuclear layer and outer nuclear layer was measured by computer-based image analytical system. Immunohistochemistry was applied to observe PEDF and VEGF. Real-time quantitative polymerase chain reaction was used to detect the expression of PEDF and VEGF mRNA. Results: The expression of CD105, CD73 and CD90 was positive, while the expression of CD34, CD45, CD11b, CD19 and HLA-DR was negative. ELISA results showed that after transfection PEDF protein expression in the supernatant of PEDF-MSC (84.09±7.07) μg/L was higher than the control group (9.03±0.14) μg/L ( P< 0.05). At 2 weeks after intravitreal injection, green fluorescence was observed in the rat vitreous of groups D and E under a fluorescence microscope; no obvious green fluorescence was found in the retina. After 2 months of intravitreal injection, the thickness of inner plexiform layer in group E was significantly decreased; the thickness of inner nuclear layer and outer nuclear layer was higher ( P< 0.05). Immunohistochemical staining showed that 2 months after intravitreal treatment, the average optical density values of PEDF were improved, but the average optical density values of VEGF were decreased in group E ( P< 0.05). Real-time polymerase chain reaction showed that 2 months after treatment, the expression level of PEDF mRNA in group E was improved, but the expression level of VEGF mRNA was decreased ( P< 0.05). Conclusions: Intravitreal injection of PEDF-MSC could up-regulate the expression of PEDF and down-regulate the expression of VEGF in diabetic rats and may represent a novel candidate resource for cell therapy of DR nerve damage. (Chin J Ophthalmol, 2017, 53, 540-547) .

Objective: To explore the inhibitory effect of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1), a novel anti-angiogenic factor, on retinal angiogenesis and its underlying molecular mechanisms. Methods: Experimental study. C57BL/6J mice were classified into three groups: control group ( n= 24), oxygen-induced retinopathy (OIR) non-intervention group ( n= 24) and OIR intervention group ( n= 72). The OIR mouse model was established using improved Smith's methods ( n= 96). Twelve-day-old mice in the OIR intervention group were randomly assigned into three groups receiving intravitreal injection of recombinant mouse IGFBP-rP1 (50 μg/L, 100 μg/L and 200 μg/L, respectively). Five days later, the proliferative neovascular responses were estimated by quantifying the new vessel area relative to the total retinal area in flattening retinas stained by high molecular FITC-Dextran and counting the number of neovascular cell nuclei breaking through the internal limiting membrane (ILM) in cross-sections. Retinal phosphor-ERK1/2 (p-ERK1/2), ERK1/2 and vascular endothelial growth factor (VEGF) protein expression was assessed by Western blot. Results: In the fluorescence angiograms, irregular neovascularization and fluorescence leakage were observed in the OIR model. In the OIR non-intervention group, the expression of p-ERK1/2 and VEGF was significantly up-regulated in comparison with the control group ( t= 100.068, P= 0.000. t= 6.526, P= 0.003). The area ratios of new retinal vessels and the number of neovascular cell nuclei in mice receiving intravitreal injection of recombinant mouse IGFBP-rP1 both decreased significantly ( F= 1920, P= 0.000. F= 852.387, P= 0.000), following the down-regulation of retinal p-ERK1/2 protein expression ( F= 859.587, P= 0.000) and VEGF protein expression ( F= 24.301, P= 0.000) in a dose-dependent manner ( P< 0.05). There was no significant difference in ERK1/2 protein expression ( P> 0.05). Conclusions: IGFBP-rP1 inhibits retinal angiogenesis by blocking ERK signaling pathway and down-regulating VEGF expression. This highlights the potential importance of IGFBP-rP1 serving as a target of gene therapy for retinal neovascularization. (Chin J Ophthalmol, 2017, 53: 207-211) .

Objective: To investigate the effect of intravitreal injection of neural stem cells (NSC) induced from human umbilical cord mesenchymal stem cells, and to provide a theoretical basis for the clinical treatment of blood-retinal barrier damage due to diabetic retinopathy (DR). Methods: Experimental study. Sixty male Sprague-Dawley rats were randomly divided into control group, DR group and NSC group. Diabetic rats were induced by injection of streptozotocin, and the control rats were injected with an equal volume of solvent. Three months after the establishment of diabetic models, the NSC group was injected with 2 μl of NSC in the right vitreous, and the DR group was injected with 2 μl of phosphate-buffered saline. One month later, all the rats were sacrificed. The retinal vessels and leakage were examined with flat-mounted retinas. Vascular permeability was quantified by analyzing albumin leakage using the Evans blue (EB) method. Retina was examined by hematoxylin and eosin staining. Results: Retinal blood vessels of the control rats were normal, with no EB leakage outside the vessels. The background fluorescence was enhanced and focal leakage and focal dilated vessels were detected in the DR group. In the NSC group, background fluorescence was enhanced slightly and EB leakage area decreased significantly compared with the DR group. The average EB in control group, DR group and NSC group were (9.91±1.53), (24.67±2.26) and (12.85±2.58)μg/g, The EB leakage in the NSC group decreased significantly compared with the DR group ( q =9.748, P< 0.05). Pathological hematoxylin and eosin staining showed that the retinal layer structure was normal and clear in the control group, the retina was thin, the cell arrangement was in disorder and the nucleus was swelling in the DR group, the status of the NSC group was between the other two groups. Conclusions: Transferring human umbilical cord mesenchymal stem cells-induced NSC in vitro to diabetic rat models by intravitreal injection could reduce leakage of blood vessels and attenuate blood-retinal barrier breakdown induced by diabetes. (Chin J Ophthalmol, 2017, 53: 53-58) .

Objective: To evaluate the effects of intravitreal injection of sterile air followed by scleral cryotherapy on simple rhegmatogenous retinal detachment (RRD)., Methods: Retrospective study. Thirty-five cases (thirty-five eyes) with RRD were collected from Oct 2013 to Mar 2014. Among them, macular detachment was observed in 31cases, all accompanied with obvious synchesis. All retinal breaks were horseshoe shaped and holes located above 9 o'clock to 3 o'clock position, with size ranged from 0.5 to 1.5 PD. Subretinal fluid was drained by scleral puncture, after that 0.5-2.0 ml sterile air was injected into the vitreous cavity. Cryotherapy was done under binocular indirect ophthalmoscope followed by scleral buckling., Results: Retina reattachment was seen in 32 cases at the first day after operation. A small amount of subretinal fluid was found in 2 cases, which absorbed completely in one week after the surgery. Vitrectomy was done in 1 case because of aggravation of vitreous opacity and failure of retinal reattachment. The success rate of single operation and final operation was 97.1% and 100.0%, respectively. Visual improvement was observed in 33 cases. Ocular hypertension was seen in 6 cases and was controlled by topical antiglaucomatous eyedrops. No recurrence of RRD was found in all cases during the 5-10 months follow-up visit., Conclusion: Gas tamponade followed by scleral cryotherapy can improve the success rate of operation for simple rhegmatogenous retinal detachment with obvious synchesis and retinal holes located at the upper quadrant.

Objective: To observe the retinal vascular development and changes on aggressive posterior retinopathy of prematurity (AP-ROP) by intravitreal ranibizumab, evaluate the therapeutic effect, and provide the basis for clinical treatment., Methods: The total of 38 eyes of 19 premature infants who were diagnosed as AP-ROP from January 2012 to October 2013 in our hospital were performed intravitreal injection of ranibizumab (0.04 ml). It was observed about the regression of plus diseases, ridges, neovascularization on the ridge and the development of peripheral retinal vessel. Laser photocoagulation were performed for 14 eyes of 7 cases whose plus diseases, ridges and neovascularization on the ridge didn't regress completely after intralvitreal injection of ranibizumab., Results: All infants were found retinopathy regressed and retinal vessels continued to develop peripherally to some degree. Of all infants, 24 eyes of 12 infants were found complete regression of retinopathy, resolution of neovascularization and bleeding and that retinal vessels continued to develop to ora serrata or scarification of peripheral retinopathy. Fourteen eyes of 7 infants were found retinopathy didn't regressed completely and regressed completely after combing intravitreal ranibizumab injection. All 19 infants didn't occure infection, ocular or systemic complications., Conclusions: The efficacy of intravitreal injection of ranibizumab is good for AP-ROP. It can made ridge, neovascularization on the ridge and plus disease regress, as well as let the retinal vessel continue development. Infants with no regressed retinopathy may need combined laser photocoagulation.

Objective: To observe the efficacy and safety of intravitreal injection of conbercept, a new drugs of VEGFR fusion proteins, on wet age-related macular degeneration (wAMD)., Methods: To analyze retrospectively the clinical data of 58 patients with wet wAMD, which was diagnosed by examination of ETDRS charts, color fundus photograph, fluorescein angiography (FFA) and optical coherence tomography (OCT), were underwent intravitreal injection conbercept 0.5 mg (0.05 ml of 10 g/L). Follow-up time was 6 to 12 months.Visual acuity (ETDRS charts letter), retinal thickness, leakage of CNV and operative complications before and after the treatment were analyzed., Results: Conbercept injection therapeutic times were 3-5, the average therapeutic times were 3.05. At the end of the follow-up period, the mean letter of ETDRS charts was 50.20±12.87, increased 26.20 letters (t=2.936, P<0.01). the ETDRS charts improved 15 or more letters in 33 eyes (53.23%), decreased more than 15 letters in 2 eyes (3.23%); the average foveal thickness on OCT images were (223±74) µm after treatment, decreased significantly (t=3.669, P<0.01) ; FFA showed CNV complete closure in 34 eyes (54.84%), partial closure in 23 eyes (37.10%), no change in 5 eyes (8.06%). IOP increased in 2 eyes after treatment and recovered within one week., Conclusions: Intravitreal injection of conbercept for wAMD was well tolerated, with an improvement in BCVA, macular edema and leakage of CNV, reduce the risk of rehaemorrhagia.

Objective: To investigate whether ranibizumab can penetrate into the retina after subconjunctival injection in a rabbit model., Methods: Experimental study. Fifty-six New Zealand rabbits were randomly divided into four groups: control group (3), saline subconjunctival injection group (3), ranibizumab intravitreal injection group (25) and ranibizumab subconjunctival injection group (25). Each rabbit received single injection in right eye. Ranibizumab's location and concentrations in the retina and aqueous humor were determined by immunofluorescence staining and ELISA at 1, 2, 4, 8, 12 weeks after injection. The comparison of ranibizumab concentration data was analyzed by t-test., Results: The concentrations of aqueous humor in intravitreal injection group, determined by ELISA, were (389.67 ± 22.55), (319.33 ± 17.93), (22.67 ± 3.06), (9.67 ± 1.53) and (7.33 ± 2.18) mg/L at 1, 2, 4, 8, 12 weeks respectively. Concentrations of subconjunctival injection group were (53.67 ± 3.21), (12.67 ± 3.06), (8.33 ± 1.53), (2.66 ± 2.08) mg/L at 1,2,4,8 weeks and had a statistical difference compared with intravitreal injection group at each time point (t = 32.96, 38.39, 7.67, 11.07, P < 0.05). But there was no detection at 12 weeks. Similar in retina immunofluorescence staining results, the ranibizumab positive signals were detected in all the time points except the last one in subconjunctival injection group., Conclusion: Subconjunctival ranibizumab injection may be able to penetrate into retina.

Incomplete perifoveal posterior vitreous detachment (PVD) associated with abnormal vitreomacular adhesion (VMA) can cause vitreomacular traction (VMT) and macular hole (MH) formation, which require vitrectomy treatment. Pharmacologic vitreolysis, which is intravitreal injection with vitreolytic enzymes to resolve VMA, may be used as an alternative therapy.Ocriplasmin, formerly known as microplasmin, is a recombinant truncated form of plasmin with proteolytic activity against fibronectin and laminin.It was recently approved for VMA treatment in the European Union and USA. Phase III studies indicated that ocriplasmin injection was a safe and effective treatment for selected cases of symptomatic VMA and MH. VMA release was achieved in 26.5% of ocriplasmin-injected eyes versus 10.1% of the placebo group. MH closure was achieved in 40.6% as compared with 10.6% of the placebo group.In comparison with the outcome after vitrectomy, the success rate of ocriplasmin was still far below expectation. Ocular adverse events included vitreous floaters, photopsia and profound visual decline. Its efficacy and safety need to be further evaluated in more clinical trials.

Objectives: To evaluate the efficacy of intravitreal carboplatin plus bevacizumab in refractory retinoblastoma., Methods: Perspective study.Eleven patients (11 eyes) with the diagnosis of refractory retinoblastoma were enrolled in Department of Ophthalmology of Peking University People's Hospital from June 2013 to March 2014. They underwent intravitreal carboplatin plus bevacizumab every 4 weeks, an average of 4.5 times of treatment.Observe for 3 months after the last treatment. Aqueous humor was taken for cytological and VEGF detection and retinal funds were taken photos for observation.Statistical analyses between experimental group and control group and before and after intravitreal injection within experimental group were performed with independent samples t test., Results: Tumor in vitreous cavity reduced significantly in seven patients, however, poor control in four cases, and three of them were recurrent after first-line treatment. Cytology detection for aqueous humor showed no tumor cells in all of them. Aqueous VEGF of patients with retinoblastoma (60.65 ± 6.20) was significantly higher than the control group (21.98 ± 6.91). The difference was statistically significant (t = 13.80, P < 0.01). And the aqueous VEGF content decreased significantly after treatment (t = 2.12, P < 0.05)., Conclusion: Intravitreal carboplatin plus bevacizumab, is a relatively safe, effective treatment for refractory retinoblastoma, however, ineffective for recurrent tumor.

Ocriplasmin is a recombinant truncated form of human serine protease plasmin with proteolytic activity to induce vitreous liquefaction and weaken vitreomacular adhesion, thereby facilitating posterior vitreous detachment and acting as a potential alternative to replace the more traumatic vitrectomy which can result in incomplete vitreoretinal separation. Intravitreal ocriplasmin for symptomatic vitreomacular adhesion has been systematically evaluated in clinical trials. Ocriplasmin at the recommended dose of a single 125 µg intravitreal injection has recently been approved for the treatment of symptomatic VMA in the USA and EU. This review is aiming to highlight the research update of ocriplasmin.

Objective: To characterize the safety profile of triamcinolone acetonide made in China (Transton) and triamcinolone acetonide acetate (Tongyong) for their ocular application., Methods: Experimental study. In vitro cell viability assay was performed on 3 types of human ocular cells to evaluate the cytotoxicity of the simulated vitreal concentrations (from a 1:15 dilution as if injected into 1.5 ml of rabbit vitreous to 1:50 dilution as if injected into 5 ml of human vitreous) of Transton and Tongyong using MTT method.In vivo 28 guinea pigs, randomly divided into four groups, were used for evaluating either intravitreal 6 µl of the two types of triamcinolone suspension or 18 µl of their supernatant. Following the injections, the eyes were monitored by biomicroscopy, ophthalmoscopy, tonometry, electroretinography, and histology. The Dunnett's test was used to analyze in vitro cell viability. Paired sample t-test and Generalized Estimating Equations (GEE) were respectively used to compare electroretinography data and intraocular pressure between experimental eyes and the control eyes., Results: The undiluted supernatant of Transton and Tongyong was toxic to human scleral fibroblasts when compared with their control groups (MTT values = 0.046 ± 0.036 and 0.044 ± 0.05 versus 0.367 ± 0.106 and 0.413 ± 0.128) (P < 0.01) or with the BSS group (0.368 ± 0.106 and 0.441 ± 0.137) (P < 0.01). 1:15 or greater dilution of supernatant of Transton and Tongyong did not show cytotoxicity on cultured human retinal pigment epithelium cells or Müller cell (P > 0.05), but 1:15 dilution of Tongyong supernatant showed cytotoxicity on the Müller cells (MTT value = 0.366 ± 0.062 versus 0.417 ± 0.042 for BSS) (P = 0.03). In vivo, neither intravitreal 6 µl (0.25 mg, equivalent to 4 mg in 0.1 ml for human eyes) of the suspension nor 18 µl (equivalent resultant preservative concentration to intravitreal 4 mg in 0.1 ml for rabbit eyes) of the supernatant of Transton and Tongyong showed ocular toxicity., Conclusion: The equivalent dose (6 µl) to 4 mg in 0.1 ml intravitreal suspension for human eye or equivalent resultant preservative concentration to 0.1 ml intravitreal suspension for rabbit eye is found safe in guinea pig eyes.

Objective: To assess efficacy of membrane peeling combined with intravitreal injection of bevacizumab in the treatment of macular epiretinal membrane., Methods: From January, 2012 to June, 2013, 33 patients (33 eyes) with the diagnosis of macular epiretinal membrane underwent vitreous surgery and membrane peeling. The patients were randomly divided into intravitreal bevacizumab group (IVB group) and non-intravitreal bevacizumab group (non-IVB group). All the patients underwent standard three-port vitrectomy and peeling of epiretinal membrane, with intravitreal injection of 1.5 mg bevacizumab at the end of operation in IVB group. The best corrected visual acuity and optical coherence tomography (OCT) were examined before and after the treatment. The patients were followed up for 3-14 months (mean 6.5 months)., Results: Macular epiretinal membranes were successfully peeled during operation in all the patients without postoperative intraocular infection or bleeding. Fifteen eyes received vitrectomy combined with intravitreal injection of bevacizumab, and 18 underwent only vitreous operation and membrane peeling. At the end of the follow up, the visual acuity improved in 11 eyes (73.3%) in IVB group, as compared to 13 eyes (72.2%) in the non-IVB group (P=0.627). Central macular thickness decreased by 143∓62 µm in IVB group and by 96∓28 µm in non-IVB group, showing a significant difference between the two groups (t=5.564, P<0.01)., Conclusion: Vitrectomy and membrane peeling combined with intravitreal injection of bevacizumab can promote the recovery of macular morphology but not visual function, and its clinical use still needs to be tested in a long-term and large-sample randomized controlled study.

It is now well recognized that vitreomacular adhesion (VMA) plays an important role in the pathogenesis of various retinopathy. Traction released through pars plana vitrectomy was used before, but it is limited by some problems such as incomplete vitreoretinal separation, vitreous remnant and other operative complications. While another new method-Pharmacologic Vitreolysis provided us a new method for persistent pathologic VMA treatment. This review aims to introduce the vitreous molecular structure, principles of posterior vitreous detachment and progression of pharmacologic vitreolysis method study.

Objective: To compare the efficacy of photodynamic therapy (PDT) alone, intravitreal anti-vascular endothelial growth factor (VEGF) therapy alone, and the combination of the two therapies for polypoid choroidal vasculopathy (PCV)., Methods: Systematic review. A computerized search was conducted in Pubmed,Biosis Preview, Cochrane Library, and Embase.Studies comparing any two of the above three treatment strategies were enrolled in the study. Meta-analysis of pairwise comparisons of the three approaches was conducted. The primary endpoint was the proportion of patients with complete regression of polyps.Other endpoints included best corrected visual acuity (BCVA), central retinal thickness (CRT), number of treatments., Results: A total of 13 comparative studies were obtained, including 1 randomized controlled trials (RCT) and 12 retrospective comparative study (RCS).Four studies compared anti-VEGF monotherapy with PDT monotherapy.Seven studies compared PDT monotherapy with combination therapy.Four studies compared anti-VEGF monotherapy with combination therapy. Considering the RCT and RCS results: PDT was superior to anti-VEGF in achieving complete regression of polyps at month 6 (P = 0.004) , although BCVA and CRT showed no significant difference at 12-month follow-up. There was no significant difference in BCVA, CRT, and the proportion of patients with complete regression of polyps between PDT and combination group at 12 months follow-up.However, combination therapy showed more promising result in improving visual acuity at 24 months (P = 0.05), with fewer PDT needed than in PDT monotherapy. Combination therapy was superior to anti-VEGF in achieving complete regression of polyps and the number of injections needed tended to be fewer. BCVA improvement and CRT reduction showed no significant difference at 12-month follow-up., Conclusion: PDT with or without anti-VEGF therapy is superior to anti-VEGF monotherapy in achieving complete polyp regression, and combination therapy appeared to result in better visual outcome than PDT monotherapy in the long term (2 years).

Objective: To investigate the electrophysiological and morphological changes of retinae after intravitreal injection of cyclosporin A (CsA) in experimental diabetic rats., Methods: Experimental study. SD diabetic mellitus (DM) rat models were induced with intraperitoneal injection of streptozotocin. The rats were divided into four groups, with 9 rats in each group:the normal control (group CON), the diabetic rats with or without CsA intravitreal injection respectively (group DM + CsA and group DM), and the diabetic rats with dimethyl sulfoxide (DMSO) intravitreal injection (group DM + DMSO). The intravitreal injection of CsA or contrast solution was performed 4 weeks after the modeling. The retinal function of rats was examined by electroretinogram (ERG) 48 hours after the intravitreal injection. All rats were sacrificed and the structural changes of retina were observed by optical and transmission electron microscope. The datas of ERG including amplitudes and latencies of a-wave and b-wave were analyzed by One-way ANOVA and Bonferroni post hoc test., Results: There was difference in ERG b-wave among the 4 groups under different stimuli light intensity (F = 14.760 - 28.890, all P value < 0.01). And there was difference in ERG a-wave among the 4 groups when the stimuli light intensity ≥ -0.35 log cd×s×m(-2) (F = 12.510, 15.500, both P value < 0.01). Comparing to the group CON (ERG a-wave: 82.43 ± 26.68, ERG b-wave: 208.40 ± 51.20), the ERG a-wave and b-wave amplitudes of group DM (ERG a-wave: 39.71 ± 7.61, ERG b-wave: 92.20 ± 24.42) and group DM + DMSO (ERG a-wave: 37.63 ± 17.25, ERG b-wave: 93.11 ± 22.50)(t = 5.448 - 7.872, all P value < 0.05), and the ERG b-wave of group DM + CsA (160.10 ± 43.39) (t = 3.299, P < 0.05) were declined in dark adaptation, while the ERG a-wave (63.91 ± 20.32) of group DM ± CsA had no difference (P > 0.05). The a-wave and b-wave amplitudes of group DM + CsA were significantly increased compared to the other two groups in dark adaptation (t = 3.203 - 4.759, both P < 0.05). Under optical microscope, group DM, DM + DMSO and DM + CsA had outer nuclear layer (ONL) disorder. Under transmission electron microscope, there were ultrastructure changes of the three groups. Furthermore, the ONL disorder and ultrastructure changes of group DM + CsA were less severe than the other two groups., Conclusions: Functional and morphological changes are evident in the early stages in DM rats. Intravitreal injection with CsA shows protective effects on the nerve function in DM retina.

Objective: To research the Mn(2+) toxicity in vivo rabbit retina. Mn(2+) is used as a tracer in MRI., Methods: It was an experimental study. Sixty pigmented rabbits (120 eyes) were divided into 5 groups randomly. Manganese chloride solution 25 µl of 10, 15, 20, 30, 40 mmol/L were injected intravitreally in one eye of each rabbit respectively as 5 experimental groups (n = 12). The saline (0.9%) 25 µl was injected intravitreally in other eye of each rabbit as control group (60 eyes). After intravitreal injections, all eyes were examined by color fundus camera, fluorescein angiography, flash electroretinography, light microscopy, and transmission electron microscopy on the 0(th), 7(th), and 28(th) day., Results: On the 7(th) day after intravitreal injection, the average of the F-ERG b-wave amplitude was reduced significantly from 337 µV to 189 µV in the group of 15 mmol/L (F = 20.43, P < 0.05), but the amplitude was returned to normal on the 28(th) day. On the 7(th) day after intravitreal injections, the F-ERG b-wave amplitude was reduced significantly in the group of ≥ 20 mmol/L, and the amplitude was not returned to normal on the 28(th) day. There were abnormal changes in the structure of the retina in ≥ 20 mmol/L group at difference time after intravitreal injections., Conclusion: MnCl(2) as a tracer in vivo optic nerve, the concentration of ≤ 15 mmol/L caused only reversible changes in retinal function; The concentration of ≥ 20 mmol/L appears, damages in retinal function and morphology appeared.

Objective: To examine the effect of genistin on traumatic proliferative vitreoretinopathy (PVR) in rabbits., Methods: Traumatic PVR was induced in pigmented rabbits by intravitreal injection of platelet rich plasma. The eyes then received an intravitreal injection of dimethyl sulfoxide (0.1 mL), 2 or 40 μg genistin (0.1 mL), and 1 mg fluorouracil(0.1 mL), respectively to form 4 groups. The eyes were examined ophthalmoscopically on distinct days after the surgery and the stage of PVR was evaluated. The model eyes and normal eyes in the 40 μg genistin group carried ERG test on the 28th day. All model eyes in the 4 groups were observed by light microscope on the 28th day., Results: In the control eyes, the retina was detached after 10 d, the PVR had progressed to higher stages with time. In the eyes injected 40 μg genistin or fluorouracil, the PVR also developed; however, the severity of PVR was lower than that in the control eyes. PVR was significantly inhibited in the 40 μg genistin group compared with the control eyes after 14 d (P<0.05). Histological examination of the genistin-treated eyes disclosed no morphological changes, and ERG analysis revealed no significant functional changes., Conclusion: Intravitreal injection of genistin is safe and effective in reducing traumatic PVR in clinical treatment.

The therapeutic effect of sustained intravitreal injectable voriconazole microspheres (VCZ-MS) on an experimental endophthalmitis of Aspergillus fumigatus was investigated. VCZ-MS was prepared successfully and its physico-chemical property was also evaluated. Right eyes of albino rabbits were infected with an intravitreal injection of 1 000 CFU x mL(-1) of susceptible Aspergillus fumigatus. All fungal endophthalmitis models were randomly divided into five groups 48 hours later: Group A is control group with no treatment; in group B, vitrectomy was performed combined with intravitreal 3 times injections of 100 microg x 0.1 mL(-1) voriconazole every other day. In group C, D and E, vitrectomy was performed combined with intravitreal injection of 0.5 mg, 1.0 mg and 1.5 mg VCZ-MS respectively. The treatment effect was assessed by slit lamp and indirect ophthalmoscope funduscopy examination, using clinical grading system of inflammation in the anterior chamber and the vitreous opacity. The optical microscopy revealed that microspheres obtained from the experiment design were opaque, discrete and spherical particles with smooth surfaces. The drug content and encapsulation efficiency of microspheres were 29.94% and 73.5%, respectively. Endophthalmitis occurred in all eyes of group A, and rapidly developed to panophthalmitis. The inflammation grade of group B, C, D or E was lower than that of group A (P < 0.05). The grade of vitreous opacity in group C, D, E is lower than group B (P < 0.05). Two eyes in group C developed to panophthalmitis. But in group D and E, all eyes whose inflammation was controlled had no recurrence with vitreous clear. Histopathological examination showed normal structures in the cured eyes, while most uncured eyes were atrophic and with eyeball destroyed. So, it can be safely concluded that the curative effect of intravitreal VCZ-MS is significantly better than that of routine intraocular injection of voriconazole. The optimal dose is the one containing 1.0 mg voriconazole.