The aim of the present study was to evaluate the 1-year outcomes of a high-dose aflibercept injection [4 mg 2+ pro re nata (PRN) scheme] for individuals with myopic choroidal neovascularization (mCNV) through optical coherence tomography (OCT) follow-ups. A total of 16 consecutive patients (7 males and 9 females; sixteen eyes) with mCNV were enrolled in this retrospective study. The mean age was 30.5±3.35 years and mean spherical equivalent was -7.31±0.90 D. Subjects received 4 mg aflibercept intravitreal injection on the day of diagnosis and 35 days later. Further injections of aflibercept were required when the following were detected by OCT and fluorescein angiography: i) Decrease in best corrected visual acuity (BCVA); ii) aggravation of metamorphopsia; iii) macular oedema; iv) macular haemorrhage; v) increase in retinal thickness; and vi) leakage. Ophthalmic examination and OCT were performed at the baseline, as well as at 1, 2, 4, 6, 8, 10 and 12 months after the initial aflibercept injection. BCVA and central retinal thickness (CRT) were evaluated at each follow-up. The results showed that the vision of all subjects improved following the aflibercept intravitreal injection. The mean BCVA improved from 0.35±0.15 logarithm of the minimal angle of resolution (logMAR) at the baseline to 0.12±0.05 logMAR at final follow-up (P<0.05). A reduction in metamorphopsia was observed and the mean CRT was reduced from 345.38±34.69 µm of pre-treatment levels to 222.75±8.98 µm at the last postoperative visit (P<0.05). The mean number of injections in the present study was 2.13±0.5. Out of all patients, 13 received two injections and 3 subjects received three injections. The mean follow-up was 13.41±1.17 months. Based on the outcomes, it was found that an intravitreal injection of high-dose aflibercept (4 mg 2+PRN scheme) is effective for vision improvement and stabilization. In addition, it also significantly alleviated metamorphopsia and reduced the CRT in patients treated with mCNV. During the follow-up, the eyesight of the patients was stable.
Patients with a refractive error of <-6 degrees or an axial length of >26.5 mm and typical pathological changes in the fundus are diagnosed with pathologic myopia (PM). PM occurs in 1-3% of adults (
In recent years, the anti-vascular endothelial growth factor (VEGF) agents used in patients with mCNV have demonstrated considerable success in visual acuity gains and have led to an improvement in the patients' quality of life (
Bevacizumab and ranibizumab, which are respectively a whole anti-VEGF antibody and an antibody fragment, have been mostly used in mCNV treatment targeting VEGF-A, according to studies conducted after 2006 (
Studies on high-dose anti-VEGF therapy used to treat neovascular AMD have been conducted. Broadhead
The number of injections varies among different studies. In the study performed by Bruè
This retrospective study reviewed the charts of patients with mCNV encountered at the Central Hospital Affiliated to Shandong First Medical University (Jinan, China) between January 2019 and August 2021. A total of 16 consecutive subjects (7 males and 9 females; age range, 26-38 years) with mCNV were enrolled in this retrospective study. The study was approved by the ethics committee of the Central Hospital Affiliated to Shandong First Medical University (Jinan, China; approval no. 2022-130-01) and was performed according to the Declaration of Helsinki. All subjects provided written informed consent prior to treatment. CNV was diagnosed by clinical examination, optical coherence tomography (OCT; Cirrus HD-OCT 4000; Carl Zeiss Meditec, Inc.) and fluorescein angiography (FA) and/or indocyanine angiography. All patients underwent computerized optometry using a Topcon KR-800 (Beijing Dakang Instrument Co., Ltd.), axial length measurement (IOLMaster®; Carl Zeiss AG) and intraocular pressure (TOPCON CT-800). The inclusion criteria were as follows: i) High myopia with a refractive error of <-6 diopters; ii) axial length of >26.5 mm; iii) myopic retinal pathological changes (posterior staphyloma, chorioretinal atrophy, papillary crescent and lacquer cracks); iv) OCT evidence of hyperreflective lesion; v) FA detection of subfoveal active CNV; and vi) BCVA of ≥0.5 logMAR prior to treatment. The exclusion criteria were as follows: i) Patients with different macular diseases, such as ARMD and diabetic macular oedema; ii) patients with previous subfoveal or juxtafoveal laser treatment; iii) history of trauma; iv) ophthalmic surgery; v) presumed ocular histoplasmosis syndrome; vi) hereditary eye disease; and vii) any other cause of secondary CNV or spheric equivalent, such as astigmatisms.
All patients received an intravitreal injection of 4 mg aflibercept (Bayer AG). The lids and conjunctiva were disinfected with 10% iodophor and 5% povidone iodine, respectively. The conjunctiva was anesthetized with 1% oxybuprocaine. Aflibercept (4 mg) was injected using a 30-g needle through the pars plana (4 mm from the limbus of the phakic eye) into the vitreous and an eye patch was placed over the eye following treatment. Gatifloxacin eye drops (China Otsuka Pharmaceutical Co., Ltd.) were prescribed to be instilled four times a day for 7 days, starting on the second day after surgery. The second injection was administered 35 days later. Ophthalmic examination and OCT were performed at the baseline and at 1, 2, 4, 6, 8, 10 and 12 months after the initial injection. At each follow-up visit, a thorough ophthalmic assessment was performed, including an evaluation of BCVA and retinal morphology with OCT. FA was performed if the activity of the lesion could not be estimated by clinical expression and OCT assessment at each follow-up visit. BCVA, macular appearance, OCT and FA findings were used to decide if the subject should have received another intravitreal injection of aflibercept. A decrease in BCVA, aggravation of metamorphopsia, presence of macular oedema or haemorrhage, increased central retinal thickness (CRT) or central macular thickness (CMT), or increased leakage created the need for additional treatment with aflibercept.
Statistical analysis using SPSS version 26.0 (IBM Corp.). All values in the text are presented as the mean ± standard deviation. The outcomes at different time-points following treatment were compared with baseline values of BCVA and CRT individually. Pairwise comparisons were performed at different postoperative time-points. The data were evaluated for normality using normality tests. Normally distributed data were assessed using repeated-measures ANOVA and pairwise comparisons were performed using Friedman's test. Homogeneity of variance was tested prior to ANOVA. Non-normally distributed data were assessed using the Kruskal-Wallis H-test. Dunn's test was used for pairwise comparisons. P<0.05 was considered to indicate a statistically significant difference.
All 16 eyes were administered an aflibercept intravitreal injection. Basic information of the two groups is provided in
The Snellen BCVA was changed into a logarithm of the minimum angle of resolution (logMAR). The changes in BCVA and CRT reached statistical significance at the 1-, 2-, 4-, 6-, 8-, 10- and 12-month follow-ups compared with the baseline. The mean BCVA improved from 0.35±0.15 logMAR at the baseline to 0.12±0.05 logMAR at the final follow-up (P<0.05;
mCNV is one of the sight-threatening complications of PM. The application of anti-VEGF drugs in choroidal neovascularization of high myopia has markedly improved the visual quality of patients, particularly the working population. Among the anti-VEGF drugs, bevacizumab and ranibizumab exhibited a similar efficacy in restoring functional and anatomical parameters. However, ranibizumab was designed and approved for ocular administration. It appears to be the preferred treatment for mCNV, as it achieves efficacy with a short treatment duration and frequency and few adverse effects (
There is now substantial evidence in favour of the use of aflibercept for mCNV. Toto
The outcomes of 16 consecutive eyes with mCNV treated with 4 mg aflibercept intravitreal injection were retrospectively reviewed and followed up for 12 months. All eyes initially underwent two injections 35 days apart, followed by an additional injection based on monthly visits. The present study revealed several clinical effects of the intravitreal injection of aflibercept in the treatment of mCNV. The BCVA improved from 0.35±0.15 logMAR at the baseline to 0.12±0.05 logMAR at the final follow-up visit. The BCVA improved significantly 1 month after the initial injection and further after the second injection. There was a significant difference in BCVA at 1 and 12 months after surgery. An ideal visual acuity was achieved and remained stable after two injections. The CRT was decreased significantly from 345.38±34.69 to 296.88±28.93 µm at 1 month after the initial injection. At 2 months after treatment, the CRT reached 255.31±24.25 µm. At 4 months from surgery, the CRT was further reduced and reached 234.56±10.74 µm. The CRT remained stable and was 222.75±8.98 µm at the 12-month follow-up visit. In the present study, the CRT reached stable levels at 2 and 4 months after the initial injection. This outcome is different from what was previously reported in the MYRROR trial (
As with any common intraocular surgery, intravitreal injections of anti-VEGF drugs are accompanied by risks of bleeding, infection, cataracts and glaucoma (
There were several limitations to the present study that may impact or influence the interpretation and generalizability of the findings. First, due to the retrospective design, the lack of randomization somewhat reduced the power of the results. Furthermore, the outcomes should be interpreted with caution due to the small sample size. As another limitation, the study lacked a control group. In addition, the follow-up time was short (12 months) and continuous follow-up is necessary. The present study also has its advantages. To the best of our knowledge, this is the first clinical observation obtained using high-dose aflibercept (4 mg) in the treatment of mCNV. According to these results, the 4 mg aflibercept 2+PRN scheme proved effective for mCNV, but future studies, require to be conducted in order to further evaluate the effect of this scheme.
In conclusion, the present study indicated that an intravitreal injection of high-dose aflibercept (4 mg 2+PRN scheme) was effective in promoting vision improvement and stabilization. It also significantly alleviated metamorphopsia and reduced the CRT in patients with mCNV. During the 12-month follow-up, the BCVA and CRT were stable. The present results suggested that the aflibercept 4 mg 2+PRN scheme may be an ideal choice for mCNV treatment, prompting further studies to evaluate the effect of this regimen.
Not applicable.
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
WZ and CH designed the study and drafted and revised the manuscript. YH and ZY performed data acquisition, analysis and interpretation. All authors have read and approved the final manuscript. CH and WZ confirm the authenticity of all the raw data.
This study followed the tenets of the Declaration of Helsinki and was approved by the ethics committee of the Central Hospital Affiliated to Shandong First Medical University (Jinan, China; approval no. 2022-130-01). Written informed consent was obtained from all patients.
Not applicable.
The authors declare that they have no competing interests.
BCVA changes following treatment with high-dose aflibercept. BCVA was significantly improved after treatment and remained stable during the 12-month follow-up. *P<0.05 vs. baseline. #P<0.05 vs. 1 month. BCVA, best-corrected visual acuity.
CRT changes following treatment with high-dose aflibercept. The CRT decreased significantly in the first 4 months after treatment and remained stable until the end of the 12-month follow-up. *P<0.05 vs. baseline; #P<0.05 vs. 1 month; $P<0.05 vs. 2 months; and ΔP<0.05 vs. 6 months. CRT, central retinal thickness.
OCT changes of a representative patient diagnosed with myopic choroidal neovascularization during the follow-up. (A) At diagnosis, OCT indicated fibrovascular pigment epithelial detachment and increased retinal thickness in the fovea. (B) At 1 month after the initial injection, OCT revealed that the fibrovascular pigment epithelial detachment partially retreated and the retinal thickness decreased. A strong dot reflection is seen at the top. OCT at (C) 2, (D) 4, (E) 6, (F) 8 and (G) 12 months after initial aflibercept injection. The distance of pigment epithelial detachment gradually decreased until it returned to normal. The magnification was 1:1. OCT, optical coherence tomography; N, nasal; T, temporal.
Baseline demographic and clinical characteristics (patients, n=16; eyes, n=16).
Characteristic | Value |
---|---|
Gender | |
Male | 7 |
Female | 9 |
Age, years | 30.5±3.35 |
Spherical equivalent, D | -7.31±0.90 |
Axial length, mm | 27.17±0.89 |
Duration of symptoms, months | 0.96±0.67 |
Number of injections | 2.13±0.5 |
Follow-up duration, months | 13.41±1.17 |
Data are presented as n or mean ± standard deviation.