ObjectiveTo evaluate the therapeutic efficacy of vitrectomy with internal limiting membrane (ILM) peeling and subretinal injection of balance salt solution (BSS) for refractory diabetic macular edema (DME).MethodsA retrospective case series study. From November 2017 to August 2018, 24 eyes of 19 patients affected with DME resistant to anti-VEGF therapy [central macualar thickness (CMT) more than 275 μm despite undergoing anti-VEGF therapy at least 3 times] in Ophtalmology Department of Central Theater Command General Hospital of Chinese People's Liberation Army were enrolled in this study. All the patients underwent 25G pars plana vitrectomy with ILM peeling and subretinal injection of BSS. The BCVA was measured using the international standard visual acuity chart, and the results were converted to the logMAR visual acuity. The CMT and the macular volume (MV) were assessed with swept-source optical coherence tomography at baseline and each month postoperatively. The differences in BCVA, CMT and MV before and after surgery were analyzed.ResultsThe mean BCVA was 0.74±0.29 at baseline, which increased significantly to 0.62±0.28, 0.56±0.25, 0.47±0.26, 0.46±0.23 at 2 weeks, 1 month, 3 months and 6 months after treatment respectively (F=4.828, P=0.001). At 6 months, BCVA improved by more than 0.3 logMAR units in 16 eyes (66.7%). The mean CMT was 554.58±102.86 μm at baseline, which reduced to 338.17±58.09 μm, 299.42±52.66 μm, 275.75±41.24 μm and 270.96±38.33 μm at 2 weeks, 1 month, 3 months and 6 months after treatment respectively (F=84.867, P＜0.001). The mean MV was 13.01±0.88 mm3 at baseline, which decreased to 11.50±0.73 mm3, 11.00±0.74 mm3, 10.68±0.61 mm3 and 10.52±0.56 mm3 at 2 weeks, 1 month, 3 months and 6 months after treatment respectively (F=47.364, P＜0.001). Macular edema recurred in 5 eyes (20.8%) 6 months after surgery. No severe systemic or ocular side effect was reported during the follow-up.Conclusions25G vitrectomy with ILM peeling and subretinal injection of BSS for refractory DME can improve the visual acuity, facilitate a rapid resolution of macular edema.
Objective To observe the clinical effect of vitrectomy, inner limiting membrane (ILM) peeling, subretinal injection of compound electrolyte intraocular irrigation solution (CEIIS) and conbercept in the treatment of diabetic macular edema (DME) with hard exudate (HE) (DME-HE). MethodsA prospective clinical study. Thirty-three patients with DME-HE diagnosed by examination in Weifang Eye Hospital from June 2020 to February 2022 were included in the study. Among them, there were 15 males (16 eyes) and 18 females (20 eyes), with the mean age of (62.00±6.54) years. All patients underwent the examinations of best corrected visual acuity (BCVA), scanning laser ophthalmoscope, optical coherence tomography (OCT), and multifocal electroretinography (mf-ERG). Snellen visual acuity chart was used for BCVA examination, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for statistic analysis. Macular foveal retinal thickness (CMT) and macular volume (MV) were measured by OCT. The 1 ring P1 wave amplitude density was measured by mf-ERG. The patients were randomly divided into group A and group B, with 17 patients (18 eyes) and 16 patients (18 eyes), respectively. There were no significant differences in age, logMAR BCVA, HE area, CMT, MV, and 1 ring P1 wave amplitude density between the two groups (t=0.403, 0.972, 0.291, 0.023, －0.268, －0.206; P＞0.05). Group A was treated with vitrectomy, ILM peeling, and subretinal injection of CEIIS and conbercept (combined therapy). Group B was treated with intravitreal injection of conbercept (IVC). Follow-up was 12 months after treatment. The changes of BCVA, HE area, CMT, MV, 1 ring P1 wave amplitude density were compared between groups and groups after treatment. The times of injection and complications after treatment were observed. Independent sample t test was used for comparison between the two groups. ResultsAt 12 months after treatment, compared to before treatment, there were significant differences in logMAR BCVA (F=14.837), HE area (χ2=94.522), CMT (χ2=199.212), MV (χ2=81.914) and 1 ring P1 wave amplitude density (F=8.933) in group A (P＜0.05); there were significant differences in CMT (F=5.540) and MV (F=7.836) in group B (P＜0.05). Compared between the two groups, logMAR BCVA: 1 week and 6 and 12 months after treatment, the difference was statistically significant (t=2.231, －2.122, －3.196; P＜0.05); HE area: except 1 week after treatment, there were statistically significant differences at other times after treatment (t=－2.422, －3.107, －3.540, －4.119; P＜0.05). CMT, MV, 1 ring P1 wave amplitude density: 12 months after treatment, the differences were statistically significant (t=－2.653, －2.455, 2.204; P＜0.05). During the follow-up period, the injection times of group A and group B were (3.06±1.89) and (5.56±2.04), respectively, and the difference was statistically significant (t=－3.815, P＜0.05). Macular hole and vitreous hematoma were found in 1 eye in group A and 1 eye in group B. ConclusionVitrectomy, ILM peeling, subretinal injection of CEIIS and conbercept to treat DME-HE can effectively remove HE, alleviate macular edema, improve BCVA, and reduce CMT and MV. Combination therapy can reduce the number of IVC re-treatments.
Gene therapy is designed to introduce genetic material into the cells of a patient via virus to enhance, inhibit, edit or add a genetic sequence, results in a therapeutic or prophylactic effect. Gene therapy has brought positive influence and great potential for the treatment of retinal diseases including genetic retinal diseases and acquired retinal diseases. In addition to the constant optimization of gene vectors, the exploration of different drug delivery techniques has brought different therapeutic effects for gene therapy of retinal diseases. The main delivery methods include subretinal injection, intravitreal injection, suprachoroidal injection. Considering the transfection efficiency and safety of delivery methods, emerging sub-inner limiting membrane injection and noninvasive gene delivery are under investigation. The selection of gene delivery method is very important for the safety and effectiveness of gene therapy for retinal diseases. It is not only related to the development of equipment and technology, but also related to the modification of adeno-associated virus, the selection of promoter and the specific retinal cells that the target gene wants to be transfected. Therefore, the most appropriate method of gene delivery should be selected according to the final gene therapy agent and the specific transfected cells after taking all these factors into consideration.
ObjectiveTo observe the effectiveness and safety of pars plana vitrectomy (PPV) combined with inner limiting membrane (ILM) removal and 41G microneedle subretinal injection of balanced salt solution (BSS) in the treatment of refractory macular hole. MethodsA prospective clinical study. From January to June 2023, 20 cases (20 eyes) of refractory macular hole patients diagnosed through examination at The Affiliated Eye Hospital of Nanchang University were included in the study. The basal diameter of the affected eye's basal diameter (BD) was ＞1 000 μm. Macular hole index (MHI) was ＜0.5. The affected eye received treatment with 23G PPV combined with ILM removal and 41G microneedle subretinal injection of BSS. Best corrected visual acuity (BCVA), microperimetry, and optical coherence tomography angiography (OCTA) were performed before and 1, 2, 3, and 6 months after surgery for the affected eye. BCVA examination was performed using standard logarithmic visual acuity chart, and convert it to logarithmic minimum resolution angle (logMAR) visual acuity for statistical purposes. MP-3 microperimetry was used for micro view examination, record the mean sensitivity (MS) of the retinal within a 12° range of the fovea. OCTA was used to measure the area of the avascular zone of the macula (FAZ), perimeter of the FAZ (PERIM), retinal vascular length density (VLD), and vascular perfusion density (VPD). The changes in BCVA, MS, FAZ area, PERIM, VLD, VPD before and after surgery were compared and analyzed. After the same time, the closure of macular hole and the occurrence of complications after surgery were observed. Single factor analysis of variance was used to compare the observation indicators at different times before and after surgery. The correlation between various observation indicators and preoperative minimum diameter (MD), BD, and hiatus height at 6 months after surgery were analyzed using Pearson correlation analysis. ResultsAmong the 20 cases with 20 eyes, there were 2 males with 2 eyes and 18 females with 18 eyes. Age was (61.45±8.56) years old. The logMAR BCVA, MS, FAZ area, PERIM, VLD, and VPD of the affected eye were 1.46±0.21, (16.20±5.81) dB、(0.40±0.17) mm2, (2.89±0.99) mm, (6.23±3.59) mm−1, (0.17±0.10)%, respectively. Six months after surgery, out of 20 eyes, macular hole closure and incomplete closure were 18 (90.0%, 18 /20) and 2 (10.0%, 2 /20) eyes, respectively. The logMAR BCVA, MS, FAZ area, PERIM, VLD, and VPD were 0.80±0.20, (22.20±4.60) dB, (0.18±0.10) mm2, (1.83±0.80) mm, (9.54±2.88) mm−1, (0.31±0.14)%. Compared with before surgery, the differences were statistically significant (P＜0.05). The correlation analysis results showed a positive correlation (P＜0.05) between preoperative BD and postoperative 6-month PERIM and VPD. There was a negative correlation between preoperative MD and postoperative VLD at 6 months (P＜0.05). There was a negative correlation between preoperative MHI and logMAR BCVA and VPD at 6 months after surgery (P＜0.05). No complications such as elevated or decreased intraocular pressure, damage to retinal pigment epithelium, retinal hemorrhage, endophthalmitis, or retinal detachment occurred after surgery in all affected eyes. ConclusionMinimally invasive PPV combined with ILM removal and 41G microneedle subretinal injection of BSS can effectively improve the closure rate of refractory macular hole patients in the short term, improve vision, and have good safety.
ObjectiveTo observe the clinical effect of subretinal injection and intravitreal injection of conbercept in the treatment of polypoid choroidal vasculopathy (PCV). MethodsA prospective, randomized double-blind controlled study. From June 2022 to January 2023, 35 patients of 35 eyes with PCV diagnosed at Affiliated Eye Hospital of Nanchang University were included in the study. All patients were first-time recipients of treatment. Best corrected visual acuity (BCVA), optical coherence tomography (OCT), and indocyanine green angiography (ICGA) were performed in all affected eyes. BCVA was performed using an international standard visual acuity chart and converted to logarithmic minimum resolved angle (logMAR) visual acuity for statistical purposes. Enhanced depth imaging with OCT instrument was used to measure the macular retinal thickness (MRT), subfoveal choroidal thickness (SFCT), and pigment epithelium detachment (PED) height. Randomized numerical table method was used to divide the patients into subretinal injection group (group A) and vitreous cavity injection group (Group B), 18 cases with 18 eyes and 17 cases with 17 eyes, respectively. Comparison of age (t=0.090), disease duration (t=−0.370), logMAR BCVA (t=−0.190), MRT (t=0.860), SFCT (t=0.247), and PED height (t=−0.520) between the two groups showed no statistically significant difference (P＞0.05). The eyes of group A were given one subretinal injection of 10 mg/ml conbercept 0.05 ml (containing conbercept 0.5 mg), and subsequently administered on demand (PRN); eyes in group B were given intravitreal injection of 10 mg/ml conbercept 0.05 ml (containing conbercept 0.5 mg). The treatment regimen was 3+PRN. Lesions were categorized into active and quiescent according to the results of post-treatment OCT and BCVA. Active lesions were treated with intravitreal injection of conbercept at the same dose as before; stationary lesions were followed up for observation. BCVA and OCT were performed at 1, 2, 3, 6 and 9 months after treatment; ICGA was performed at 3, 6 and 9 months. BCVA, MRT, SFCT, and PED height changes before and after treatment were compared and observed in the affected eyes of the two groups. Independent sample t-test was used to compare between the two groups. ResultsWith the prolongation of time after treatment, the BCVA of the affected eyes in groups A and B gradually increased, and the MRT, SFCT, and PED height gradually decreased. Compared with group B, at 2, 3, 6, and 9 months after treatment, the BCVA of group A was significantly improved, and the difference was statistically significant (t=−2.215, −2.820, −2.559, −4.051; P＜0.05); at 1, 2, 3, 6, and 9 months after treatment, the MRT of the affected eyes in group A (t=−2.439, −3.091, −3.099, −3.665, −5.494), SFCT (t=−3.370, −3.058, −3.268, −4.220, −4.121), and PED height (t=−3.460, −4.678, −4.956, −5.368, −6.396) were significantly reduced, and the differences were statistically significant (P＜0.05). No complications such as intraocular inflammation, high intraocular pressure, or vitreous hemorrhage occurred in any of the affected eyes during or after treatment. ConclusionCompared with the intravitreal injection of conbercept, the subretinal injection of conbercept can more effectively reduce the height of MRT, SFCT, PED height, and improve the visual acuity of the affected eyes with PCV.
ObjectiveTo observe the safety of 2-port non-vitrectomized subretinal injection (SRI) for the treatment of Bietti crystalline dystrophy (BCD). MethodsA exploratory clinical study. From February to May 2023, 6 BCD patients with 6 eyes who were confirmed by examination in Xiamen Eye Center of Xiamen University and were treated with SRI adeno-associated virus vector transgenic drugs were included in the study. Among them, 2 males had 2 eyes and 4 females had 4 eyes. Age were 34-60 years old. The study eye underwent adeno associated virus gene therapy via 2-port non-vitrectomized SRI. Two scleral ports were created using 25G vitrectomy trocar to place the light pipe and injection cannula. Anterior chamber paracentesis was performed to lower intraocular pressure. Under the silicone oil infusion mode of the vitrectomy machine, a 38G injection cannula penetrated the retina to reach the subretinal space. The injection speed was controlled by the foot pedal of the vitrectomy machine, and the drug was slowly injected into the subretinal space to create a subretinal bleb. if intra-ocular pressure assessed by finger palpation was high at the end of injection, drainage of the aqueous humor can be made by compressing the cornea incision until the intraocular pressure was normal. Patients were followed for 9-12 months and be examined using the same equipment and methods as before. ResultsRetinal pigment epithelium and choroidal atrophy were observed in all 6 eyes of 6 patients were graded as stage Ⅲ by the fundus examination revealing atrophy of retinal pigmented epithelium and choroid, with or without yellow-white crystals and/or complex lipid. The range were operation time 9-14 minutes. No vitreous prolapse, retinal hemorrhage, or retinal tear was observed during surgery. After 24 hours, optical coherence tomogrophy examination showed absorption of subretinal fluid and retinal reattachment. None of the six patients showed corneal keratic precipitates, anterior chamber cells, vitreous cells, inflammation, high intraocular pressure, or retinal tear within the 9-month follow-up. ConclusionSubretinal injection without vitrectomy using two ports is a safe and feasible alternative for adult gene therapy, and it shortens the surgical time.
Objective To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV). MethodsA prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance. ResultsEighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA (F=50.298) gradually increased, CRT (F=25.220), PED height (F=144.16), SFCT (F=69.77), LVCT (F=136.69), CVI (F=72.70) gradually decreased after treatment. The differences were statistically significant (P＜0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. ConclusionSubretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.
ObjectiveTo evaluate the efficacy and safety of 41G ultramicroneedle subretinal injection of balanced salt solution (BSS) in the treatment of large diameter macular holes (MH). MethodsA prospective clinical intervention study. A total of 22 eyes of 22 large-diameter full-layer MH patients diagnosed by examination in Tianjin Eye Hospital from March to June 2024 were included in the study. Twenty-two eyes with large diameter full-thickness MH were included in the study. The minimum diameter of MH in the affected eyes was all greater than 400 μm. The affected eyes received 25G pars plana vitrectomy combined with internal limiting membrane peeling and 41G ultramicroneedle subretinal injection of BSS. The affected eyes underwent best-corrected visual acuity (BCVA), microperimetry, fundus autofluorescence, and optical coherence tomography (OCT) examinations before and 1 and 3 months after surgery. BCVA was measured using the standard logarithmic visual acuity chart and converted to logarithm of the minimum angle of resolution (logMAR) visual acuity for statistical analysis. The minimum and base diameter of MH were measured using OCT. Microperimetry was performed using a macular integrity assessment device, recording the macular integrity index (MII) and macular threshold (MT) within 10° of the macular. The changes in BCVA, MII, MT, and the closure of MH and the occurrence of complications were compared and analyzed before and after surgery. For the comparison of the same continuous indicators before and after surgery, Student's t-test was used if the data were normally distributed and had equal variances, and the Mann-Whitney U test was used if the data were not normally distributed; the correlation between different indicators was analyzed using Pearson correlation analysis. ResultsAmong the 22 cases (22 eyes), there were 4 males and 18 females; all were unilaterally affected. The age was 66 (60, 71) years. The duration of the disease was 5 (2.5, 12.0) months. The logMAR BCVA of the affected eyes was 1.24±0.57, and the MII and MT were 100.0 (99.53, 100.00) and 19.0 (13.23, 21.78) dB, respectively. One month after surgery, all MH were closed, with 20 (90.91%, 20/22) and 2 (9.09%, 2/22) eyes classified as typeⅠand Ⅱ closure, respectively. At the last follow-up, the logMAR BCVA was 0.62±0.58, and the MII and MT were 99.9 (59.45, 100.00) dB and 23.6 (19.33, 26.25) dB, respectively; compared with before surgery, the logMAR BCVA (t=3.579), MII (Z=－2.374), and MT (Z=－2.997) were significantly improved, and the differences were all statistically significant (P＜0.05). Correlation analysis showed that postoperative BCVA was significantly positively correlated with preoperative BCVA (r=0.41), the minimum and base diameter of MH (r=0.64, 0.58), disease duration (r=0.63), and age (r=0.50) (P＜0.05). No surgery-related complications occurred in all affected eyes during the follow-up period. Conclusion41G ultramicroneedle subretinal injection of BSS can effectively improve the hole closure rate of large diameter MH-affected eyes in the short term, improve visual function, and has good safety.