Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis.

Background: Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) can reduce oedema, improve vision, and prevent further visual loss. These drugs have replaced laser photocoagulation as the standard of care for people with DMO. In the previous update of this review, we found moderate-quality evidence that, at 12 months, aflibercept was slightly more effective than ranibizumab and bevacizumab for improving vision in people with DMO, although the difference may have been clinically insignificant (less than 0.1 logarithm of the minimum angle of resolution (logMAR), or five Early Treatment Diabetic Retinopathy Study (ETDRS) letters, or one ETDRS line). Objectives: The objective of this updated review was to compare the effectiveness and safety of the different anti-VEGF drugs in RCTs at longer followup (24 months). Search methods: We searched various electronic databases on 8 July 2022. Selection criteria: We included randomised controlled trials (RCTs) that compared any anti-angiogenic drug with an anti-VEGF mechanism of action versus another anti-VEGF drug, another treatment, sham, or no treatment in people with DMO. Data collection and analysis: We used standard Cochrane methods for pairwise meta-analysis and we augmented this evidence using network meta-analysis (NMA) methods. We used the Stata 'network' meta-analysis package for all analyses. We used the CINeMA (Confidence in Network Meta-Analysis) web application to grade the certainty of the evidence. Main results: We included 23 studies (13 with industry funding) that enrolled 3513 people with DMO (median central retinal thickness (CRT) 460 microns, interquartile range (IQR) 424 to 482) and moderate vision loss (median best-corrected visual acuity (BCVA) 0.48 logMAR, IQR 0.42 to 0.55. One study that investigated ranibizumab versus sham and one study that mainly enrolled people with subclinical DMO and normal BCVA were not suitable for inclusion in the efficacy NMA. Consistent with the previous update of this review, we used ranibizumab as the reference drug for efficacy, and control (including laser, observation, and sham) as the reference for systemic safety. Eight trials provided data on the primary outcome (change in BCVA at 24 months, in logMAR: lower is better). We found no evidence of a difference between the following interventions and ranibizumab alone: aflibercept (mean difference (MD) -0.05 logMAR, 95% confidence interval (CI) -0.12 to 0.02; moderate certainty); bevacizumab (MD -0.01 logMAR, 95% CI -0.13 to 0.10; low certainty), brolucizumab (MD 0.00 logMAR, 95% CI -0.08 to 0.07; low certainty), ranibizumab plus deferred laser (MD 0.00 logMAR, 95% CI -0.11 to 0.10; low certainty), and ranibizumab plus prompt laser (MD 0.03 logMAR, 95% CI -0.04 to 0.09; very low certainty). We also analysed BCVA change at 12 months, finding moderate-certainty evidence of increased efficacy with brolucizumab (MD -0.07 logMAR, 95%CI -0.10 to -0.03 logMAR), faricimab (MD -0.08 logMAR, 95% CI -0.12 to -0.05), and aflibercept (MD -0.07 logMAR, 95 % CI -0.10 to -0.04) compared to ranibizumab alone, but the difference could be clinically insignificant. Compared to ranibizumab alone, NMA of six trials showed no evidence of a difference with aflibercept (moderate certainty), bevacizumab (low certainty), or ranibizumab with prompt (very low certainty) or deferred laser (low certainty) regarding improvement by three or more ETDRS lines at 24 months. There was moderate-certainty evidence of greater CRT reduction at 24 months with brolucizumab (MD -23 microns, 95% CI -65 to -1 9) and aflibercept (MD -26 microns, 95% CI -53 to 0.9) compared to ranibizumab. There was moderate-certainty evidence of lesser CRT reduction with bevacizumab (MD 28 microns, 95% CI 0 to 56), ranibizumab plus deferred laser (MD 63 microns, 95% CI 18 to 109), and ranibizumab plus prompt laser (MD 72 microns, 95% CI 25 to 119) compared with ranibizumab alone. Regarding all-cause mortality at the longest available follow-up (20 trials), we found no evidence of increased risk of death for any drug compared to control, although effects were in the direction of an increase, and clinically relevant increases could not be ruled out. The certainty of this evidence was low for bevacizumab (risk ratio (RR) 2.10, 95% CI 0.75 to 5.88), brolucizumab (RR 2.92, 95% CI 0.68 to 12.58), faricimab (RR 1.91, 95% CI 0.45 to 8.00), ranibizumab (RR 1.26, 95% CI 0.68 to 2.34), and very low for conbercept (RR 0.33, 95% CI 0.01 to 8.81) and aflibercept (RR 1.48, 95% CI 0.79 to 2.77). Estimates for Antiplatelet Trialists Collaboration arterial thromboembolic events at 24 months did not suggest an increase with any drug compared to control, but the NMA was overall incoherent and the evidence was of low or very low certainty. Ocular adverse events were rare and poorly reported and could not be assessed in NMAs. Authors' conclusions: There is limited evidence of the comparative efficacy and safety of anti-VEGF drugs beyond one year of follow-up. We found no clinically important differences in visual outcomes at 24 months in people with DMO, although there were differences in CRT change. We found no evidence that any drug increases all-cause mortality compared to control, but estimates were very imprecise. Evidence from RCTs may not apply to real-world practice, where people in need of antiangiogenic treatment are often under-treated, and the individuals exposed to these drugs may be less healthy than trial participants.

Tratamento do olho cego doloroso por glaucoma neovascular com ciclofotocoagulação transescleral / Transescleral cyclophotocoagulation treatment for painful eye with glaucoma neovascular

Resumo Objetivo: Avaliar a efetividade e o perfil de segurança da ciclofotocoagulação transescleral padrão (CTCTE) e sua variação técnica denominada slow cooking (CTCTE SC) em pacientes com olho cego doloroso por glaucoma neovascular. Métodos: Pacientes foram submetidos a exame oftalmológico, graduando o nível da dor através de escala gráfica/numérica e divididos em dois grupos, um para tratamento com CTCTE e outro CTCTE SC. O acompanhamento foi realizado no primeiro, trigésimo e nonagésimo dias. Resultados: Dos 26 pacientes inclusos, 11 (42,3%) eram do sexo masculino. A idade média dos pacientes foi de 69 anos. Destes, 16 pacientes foram submetidos ao tratamento CTCTE e 10 pacientes a CTCTE SC. A pressão intraocular (PIO) teve média pré tratamento de 49 ± 23 mmHg no grupo CFCTE e medias no 1º, 30º e 90º dias pós-operatórios respectivamente: 32 ± 24 mmHg, 38 ± 18 mmHg, 43 ± 10 mmHg. No grupo submetido a técnica CFCTE SC a PIO prévia foi 54 ± 16 mmHg e médias no 1º, 30º e 90º dias pós-operatórios respectivamente: 38 ± 22 mmHg, 39 ± 10 mmHg , 44 ± 09 mmHg. A redução da dor foi efetiva em 88,4% pacientes. Durante o pós-operatório foi verificado hiperemia, quemose e hifema. Não foram observadas complicações graves. Conclusão: O tratamento do olho cego doloroso com ciclofotocoagulação transescleral com baixa carga foi um procedimento seguro e eficaz na resolução da dor, mas apresentou um baixo nível de redução da pressão intraocular em ambas técnicas usadas.

Abstract Objective: To evaluate the effectiveness and safety profile of standard transescleral cyclophotocoagulation (CTCTE) and its technical variation of slow cooking (CTCTE SC) in patients with neovascular glaucoma pain. Methods: Patients underwent ophthalmological examination, grading their pain level through a graphical / numerical scale and divided into two groups, one for treatment with CTCTE and another CTCTE SC. Follow-up was performed on the first, thirtieth and ninetieth days. Results: Of the 26 patients included, 11 (42.3%) were male. The average age of the patients was 69 years. Of these, 16 patients underwent CTCTE treatment and 10 patients underwent CTCTE SC. Intraocular pressure (IOP) had a mean pre-treatment of 49 ± 23 mmHg in the CFCTE group and medians at the 1st, 30th and 90th postoperative days respectively: 32 ± 24 mmHg, 38 ± 18 mmHg, 43 ± 10 mmHg. In the group submitted to the CFCTE SC technique, the previous IOP was 54 ± 16 mmHg and averages on the 1st, 30th and 90th postoperative days respectively: 38 ± 22 mmHg, 39 ± 10 mmHg, 44 ± 09 mmHg. Pain reduction was effective in 88.4% patients. During the postoperative period, hyperemia, chemosis and hyphema were observed. No serious complications were observed. Conclusion: Painful blind eye treatment with low load transscleral cyclophotocoagulation was a safe and effective procedure for pain resolution, but presented a low level of intraocular pressure reduction in both techniques used.

Comparison of the efficacy of multi-point or single-point mode of 577 nm laser in the treatment of diabetic retinopathy / 中华眼底病杂志

Objective To compare the therapeutic effects of 577 nm laser panretinal photocoagulation (PRP) between one time multi-point scanning mode and multiple time single-point mode in the treatment of eyes with non-proliferative diabetic retinopathy (NPDR).Methods This is a prospective controlled study from August 2013 to February 2014.A total of 29 patients (46 eyes) with clinically diagnosed severe NPDR were randomly divided into two groups including the treatment group (12 patients,22 eyes) and the control group (17 patients,224 eyes).The treatment group received one time PRP of multi-point scanning mode,and the control group received 3-4 times of PRP with single-point mode.In order to evaluate its efficacy,the best corrected visual acuity was measured before treatment,and 1 day,1,2,6 and 12 months after treatment.The average threshold sensitivity,a/b-wave amplitude of flash ERG (F-ERG) in the 30 °-60 ° visual field,and fundus fluorescein angiography (FFA) of the change were also compared between the 2 groups.The laser energy and the number of laser spots were compared,and the laser energy density was calculated.Results The response rate was 86.4％ and 79.2％,respectively in the treatment and control group,the difference was not statistically significant (x2 =0.414,P＞0.05).Compare to the pre-treatment measurement,the average threshold sensitivity,a/b-wave amplitude of F-ERG in the 30 °-60 ° visual field were reduced at 1 day after treatment both in treatment and control group,the differences were statistically significant (P＜0.05).The average threshold sensitivity,a/b-wave amplitude of F-ERG were no difference between treatment and control group at 2m,6m and 12m after treatment (P＞0.05).The average laser power,number of laser spots and energy density were (537.50 ± 64.69) mW and (339.09 ± 132.09) mW,(1934.32 ± 426.38) points and (2061.42 ± 375.49) points,(0.35±0.12) mW o ms/μm2 and (1.95 ± 0.86) mW · ms/μm2 in the treatment group and the control group,respectively.The average laser power and energy density was statistically different between the 2 groups (P＜0.05),while the number of laser spots was no difference (P＞0.05).Conclusions 577 nm multi-point scanning laser can complete the PRP at one time,and achieve the same therapeutic outcomes with the single-point mode which need several times to complete the PRP in the eyes with severe NPDR,and have lower energy density,and thus relative minor function damage.

Standardization of laser treatment for diabetic retinopathy and other ocular fundus diseases / 中华眼底病杂志

Pan-retinal photocoagulation (PRP) and macular photocoagulation (MPC) are the gold standard treatments for proliferative diabetic retinopathy (DR) and diabetic macular edema. With the development of equipment and technology advancement, photocoagulation has been gradually applied in many Eye Centers all over China. However, there are still several problems such as no standardized guideline and undesirable therapeutic effects. In this article we will summarize the indications and techniques of photocoagulation, and when and how to apply drug treatments for retinal diseases; aim at improving the criterion and clinical effects of photocoagulation.

Intravitreal triamcinolone injection combined with or without macular grid laser photocoagulation to treat macular edema / 中华眼底病杂志

Objective To compare the efficacy of intravitreal triamcinolone(IVTA) injection and IVTA combined with macular laser grid photocoagulation (MLGP) to treat macular edema.Methods Consecutive 89 patients (109 eyes)diagnosed with macular edema by examinations of ocular fundus and optical coherence tomography (OCT).The visual acuity was hand moving- 0.8 (0.19±0.13);the intraocular pressure(IOP)ranged from 7 mm Hg to 21 mm Hg(1 mm Hg=0.133 kPa)and the average IOP was 13.78 mm Hg.All the patients received OCT and microperimetry examinations,the central macular thickness was (570±182) μm;the average light sensitivity was (5.07±3.94) dB and the fixation percentage was 70.67% within 4 ° area around the macular fovea.All the patients received IVTA treatment,39 patients (48 eyes)further received MLGP 1 month later (IVTA-MLGP group).The remaining 50 patients (61 eyes) without MLGP treatment was the IVTA group.Best corrected visual acuity (BCVA),lOP,lens,OCT and microprimetry examinations before and after IVTA (1,3,6,12 months) were followed and analyzed.Results On the 12th months,the BCVA in IVTA-MLGP and IVTA group was (0.41±0.20),(0.24±0.19) respectively (P<0.05);the central macular thickness was (309±187) and (487±206) μm respectively(P<0.05);the mean light sensitivity of 4° central macular was (8.24±4.64)and(6.30±3.22) dB respectively (P<0.05);the fixation percentage was (87.01±19.70)% and (78.85±20.41) % respectively (P<0.05).During the follow-up recurrent macular edema was noticed in 28 eyes of IVTA group and 8 eyes of IVTA-MLGP group.Conclusions IVTA combined with MLG was more effective than IVTA to cure macular edema.

Understanding the pathogenesis of various type in exudative AMD, using the rational therapy / 中华眼底病杂志

Up-regulation of vascular endothelial growth factor(VEGF)is demonstrated to be a key role in formation process of intraocular neovascularization.Anti-VEGF treatment is the breakthrough of intraocular neovascular diseases therapy.Intravitreal injection of anti-neovascularization drug looks to be an effective method on ocular neovascular diseases which with the advantages of good biocompatibility,low prices and longer intravitreal half-time etc.However,at present,it lack of multi-center study;the long-term efficacy and the systematic safety needs the further clinicsl verification.Various types of CNV showed the different therapeutic reactions to either PDT or Anti-VEGF agent,the treatment methods for exudative AMD include laser,PDT,and drug like Triamcinolone Acetonide,several anti-VEGF preparations.Therefore.understanding the pathogenesis of neovascular AMD and choosing a reasonable therapeutic methods are necessary.We should try to explore a safe,effective,economic,new approach.