Importance of fluorescein angiography as a predictor of treatment response in patients with pachychoroid neovasculopathy.

The purpose of this study was to evaluate the treatment outcomes of patients with pachychoroid neovasculopathy (PNV) who received photodynamic therapy (PDT) combined with intravitreal anti-vascular endothelial growth factor (VEGF) agents, with a particular focus on the fluorescein angiography (FA) findings. We retrospectively studied 33 eyes of 32 consecutive treatment-naïve patients with PNV who were scheduled for PDT combined with anti-VEGF agents between November 2017 and May 2022, with a follow-up period of 1 year or longer. We classified patients into two groups: central serous chorioretinopathy (CSC)-dominant type and macular neovascularization (MNV)-dominant type based on the baseline FA findings. The best-corrected visual acuity (BCVA) was compared before treatment and at 3, 6, and 12 months after the initial treatment. Additionally, recurrence rate, and number of additional injections during the maintenance phase were assessed. We classified 19 eyes with the CSC-dominant type, and 14 eyes with the MNV-dominant type. The BCVA improved significantly 1 year after the initial treatment only in the CSC-dominant type (P = 0.001). The recurrence rate in the maintenance phase was lower in the CSC-dominant type (15.8%) compared to the MNV-dominant type (57.1%), a difference that reached significance (P = 0.024).This study highlights the distinct treatment outcomes between the CSC-dominant and MNV-dominant types; specifically, CSC-dominant type had better visual improvement and a lower recurrence rate than the MNV-dominant type. These differences underscore the potential of FA as a useful biomarker to predict visual outcomes and recurrence in the maintenance phase in patients with PNV.

Maruyama-Inoue M ，Yanagi Y ，Inoue T ，Kitajima Y ，Kadonosono K ... -  《Scientific Reports》

The impact of Vitreo-Macular interface abnormalities on the response to Anti-VEGF therapy for centre involving diabetic macular oedema.

The influence of Vitreomacular Interface Abnormalities (VMIA) such as Epiretinal Membrane (ERM) and/or vitreomacular traction (VMT) on the response of patients with Centre Involving Diabetic Macular Edema (CIDME) to standard of care Anti-VEGF medications is under-researched. The aims of this study were: 1) To determine the incidence of VMIA at baseline and 12 months amongst treatment naive patients commencing anti-VEGF treatment 2) To compare the response to Anti-VEGF medications at 3 monthly intervals for 12 months in a large cohort of patients with and without VMIA on their baseline OCT scan. Response was determined in terms of: number of injections, central macular thickness and visual acuity. A retrospective case notes review of treatment naïve patients with newly diagnosed CIDME. Included patients had been commenced on intravitreal Anti-VEGF injections (ranibizumab or aflibercept) at a single centre. Inclusion criteria were: treatment naïve DME patients with a CMT of 400μ or more receiving anti-VEGF treatment with at least 12 months follow up and in whom macular OCT scans and visual acuity (VA) measurements were available within two weeks of baseline, 3, 6, 9 and 12 months. Exclusion criteria included: previous intravitreal therapy, previous vitrectomy, cataract surgery during the follow-up period, concurrent eye conditions affecting vision or CMT. 119 eyes met the inclusion criteria and underwent analysis. Groups were comparable in their baseline demographics. Baseline CMT measurements were comparable at baseline (417μ and 430μ in the No-VMIA and VMIA groups respectively) and improved to approximately 300μ in both groups. From 6 months CMT continued to improve in the no-VMIA while progressively deteriorating in the VMIA group. Change in CMT was statistically different at 12 months between the 2 groups (108μ and 79μ, p= 0.04). There was a mean of 7 injections after 12 months. Our study has shown a 46% incidence of VMIA amongst patients newly diagnosed with centre involving DME undergoing treatment with anti-VEGF injections. We have also demonstrated a significant difference in CMT and VA response to anti-VEGF treatment in patients with and without VMIA. Initial response was similar between the 2 groups up until 6 months. From 6 to 12 months significant differences in treatment response emerged. Differences in clinical response between patients with and without VMIA may help guide further prospective controlled studies and optimise treatment strategies.

Maguire M ，Laidlaw D ，Davies N ，Hammond C ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

Effects on corneal endothelium of intravitreal injection of anti-VEGF drugs.

Malvasi M ，Calandri A ，Pacella E ，Vingolo EM ... -  《-》

Anti-vascular endothelial growth factors in combination with vitrectomy for complications of proliferative diabetic retinopathy.

Vitrectomy is an established treatment for the complications of proliferative diabetic retinopathy (PDR). However, a number of complications can occur during and after vitrectomy for PDR. These include bleeding and the creation of retinal holes during surgery, and bleeding, retinal detachment and scar tissue on the retina after surgery. These complications can limit vision, require further surgery and delay recovery. The use of anti-vascular endothelial growth factor (anti-VEGF) agents injected into the eye before surgery has been proposed to reduce the occurrence of these complications. Anti-VEGF agents can reduce the amount and vascularity of abnormal new vessels associated with PDR, facilitating their dissection during surgery, reducing intra- and postoperative bleeding, and potentially improving outcomes. To assess the effects of perioperative anti-VEGF use on the outcomes of vitrectomy for the treatment of complications for proliferative diabetic retinopathy (PDR). We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 22 June 2022. We included randomised controlled trials (RCTs) that looked at the use of anti-VEGFs and the incidence of complications in people undergoing vitrectomy for PDR.   DATA COLLECTION AND ANALYSIS: Two review authors independently assessed and extracted the data. We used the standard methodological procedures expected by Cochrane. The critical outcomes of the review were the mean difference in best corrected visual acuity (BCVA) between study arms at six (± three) months after the primary vitrectomy, the incidence of early postoperative vitreous cavity haemorrhage (POVCH, within four weeks postoperatively), the incidence of late POVCH (occurring more than four weeks postoperatively), the incidence of revision surgery for POVCH within six months, the incidence of revision surgery for recurrent traction/macular pucker of any type and/or rhegmatogenous retinal detachment within six months and vision-related quality of life (VRQOL) measures. Important outcomes included the proportion of people with a visual acuity of counting fingers (1.8 logMAR or worse), the number of operative retinal breaks reported and the frequency of silicone oil tamponade required at time of surgery. The current review includes 28 RCTs that looked at the pre- or intraoperative use of intravitreal anti-VEGFs to improve the outcomes of pars plana vitrectomy for complications of PDR. The studies were conducted in a variety of countries (11 from China, three from Iran, two from Italy, two from Mexico and the remaining studies from South Korea, the UK, Egypt, Brazil, Japan, Canada, the USA, Indonesia and Pakistan). The inclusion criteria for entry into the studies were the well-recognised complications of proliferative retinopathy: non-clearing vitreous haemorrhage, tractional retinal detachment involving the macula or combined tractional rhegmatogenous detachment. The included studies randomised a total of 1914 eyes.  We identified methodological issues in all of the included studies. Risk of bias was highest for masking of participants and investigators, and a number of studies were unclear when describing randomisation methods and sequence allocation. Participants receiving intravitreal anti-VEGF in addition to pars plana vitrectomy achieved better BCVA at six months compared to people undergoing vitrectomy alone (mean difference (MD) -0.25 logMAR, 95% confidence interval (CI) -0.39 to -0.11; 13 studies, 699 eyes; low-certainty evidence). Pre- or intraoperative anti-VEGF reduced the incidence of early POVCH (12% versus 31%, risk ratio (RR) 0.44, 95% CI 0.34 to 0.58; 14 studies, 1038 eyes; moderate-certainty evidence). Perioperative anti-VEGF use was also associated with a reduction in the incidence of late POVCH (10% versus 23%, RR 0.47, 95% CI 0.30 to 0.74; 11 studies, 579 eyes; high-certainty evidence). The need for revision surgery for POVCH occurred less frequently in the anti-VEGF group compared with control, but the confidence intervals were wide and compatible with no effect (4% versus 13%, RR 0.44, 95% CI 0.15 to 1.28; 4 studies 207 eyes; moderate-certainty evidence). Similar imprecisely measured effects were seen for revision surgery for rhegmatogenous retinal detachment (5% versus 11%, RR 0.50, 95% CI 0.15 to 1.66; 4 studies, 145 eyes; low-certainty evidence).  Anti-VEGFs reduce the incidence of intraoperative retinal breaks (12% versus 31%, RR 0.37, 95% CI 0.24 to 0.59; 12 studies, 915 eyes; high-certainty evidence) and the need for silicone oil (19% versus 41%, RR 0.46, 95% CI 0.27 to 0.80; 10 studies, 591 eyes; very low-certainty evidence). No data were available on quality of life outcomes or the proportion of participants with visual acuity of counting fingers or worse. The perioperative use of anti-VEGF reduces the risk of late POVCH, probably results in lower early POVCH risk and may improve visual outcomes. It also reduces the incidence of intraoperative retinal breaks. The evidence is very uncertain about its effect on the need for silicone oil tamponade. The reported complications from its use appear to be low. Agreement on variables included and outcome standardisation is required in trials studying vitrectomy for PDR.

Dervenis P ，Dervenis N ，Smith JM ，Steel DH ... -  《Cochrane Database of Systematic Reviews》