Deep Learning in Neovascular Age-Related Macular Degeneration.

Background and objectives: Age-related macular degeneration (AMD) is a complex and multifactorial condition that can lead to permanent vision loss once it progresses to the neovascular exudative stage. This review aims to summarize the use of deep learning in neovascular AMD. Materials and Methods: Pubmed search. Results: Deep learning has demonstrated effectiveness in analyzing structural OCT images in patients with neovascular AMD. This review outlines the role of deep learning in identifying and measuring biomarkers linked to an elevated risk of transitioning to the neovascular form of AMD. Additionally, deep learning techniques can quantify critical OCT features associated with neovascular AMD, which have prognostic implications for these patients. Incorporating deep learning into the assessment of neovascular AMD eyes holds promise for enhancing clinical management strategies for affected individuals. Conclusion: Several studies have demonstrated effectiveness of deep learning in assessing neovascular AMD patients and this has a promising role in the assessment of these patients.

Comparison of Functional, Structural, and Microvascular Features in Different Stages of Idiopathic Epiretinal Membrane.

Background: Idiopathic epiretinal membrane (ERM) often leads to visual symptoms such as metamorphopsia and decreased central vision. This study aimed to evaluate functional, structural, and microvascular characteristics in patients with different stages of idiopathic ERM who were candidates for surgery, with a focus on identifying potential indicators for surgical timing. Methods: A retrospective cohort study was conducted on consecutive patients with unilateral idiopathic ERM who were candidates for surgery. Patients underwent comprehensive ophthalmological assessments, including OCT grading, reading performance evaluation, and OCT angiography. Data analysis included comparisons between different ERM stages for functional, structural, and microvascular parameters. Results: A total of 44 eyes were included, classified into four ERM stages according to the Govetto grading system. Functional parameters, including distance and near visual acuity, worsened significantly with higher ERM stages, particularly in the transition from Stage 3 to Stage 4. Structural assessments revealed significant increases in central macular thickness (CMT) from Stage 3 to Stage 4. No significant differences were observed in microvascular features across different ERM stages. Conclusions: This study highlights the significant functional and anatomical impact of OCT staging in idiopathic ERM, particularly during the transition from Stage 3 to Stage 4, characterized by notable reductions in visual acuity and increases in CMT. These findings underscore the importance of considering both functional and structural parameters in surgical decision-making for ERM management. However, further research with larger cohorts is needed to confirm these observations and inform clinical practice.

Mucopolysaccharidosis type II B complicated by optic disc swelling, pigmentary retinopathy and macular edema.

PURPOSE: To report clinical and imaging features of optic nerve and retinal involvement in a patient with mucopolysaccharidosis (MPS) type II B. METHODS: A 27-year-old man, diagnosed with MPS type II B and undergoing enzymatic substitution therapy for the past 19 years, was referred to the retina service. An ophthalmological evaluation, which included multimodal imaging, was conducted to investigate potential retinal and optic disc involvement. RESULTS: The eye examination revealed a pigmentary retinopathy with a predominant loss of the outer retinal loss, primarily in the parafoveal and perifoveal regions. Notably, multimodal imaging identified macular edema without any signs of leakage, implying an association between macular edema and retinal neurodegeneration. Additionally, both eyes exhibited an optic disc with blurred margins. CONCLUSION: We herein describe the multimodal imaging findings of retinal and optic disc involvement in a patient with MPS type II B. This report describes for the first-time the presence of macular edema without leakage alongside photoreceptor damage and optic disc swelling.

Retinal OCT biomarkers associated with reading performance in patients with persistent vs. resolved diabetic macular edema.

BACKGROUND: Recent advancements in imaging technologies, particularly structural optical coherence tomography (OCT), have improved the understanding of diabetic macular edema (DME) pathophysiology and provided valuable biomarkers for disease progression and visual outcomes. This prospective study aimed to investigate the association between specific retinal biomarkers identified through OCT imaging and reading performance metrics in patients with previously treated persistent versus resolved DME and good visual acuity. METHODS: Forty-nine eyes from 35 patients with a history of DME were enrolled. Reading performance was assessed using the Radner reading charts, which include standardized sentences with geometrically progressing print sizes. Structural alterations in the inner and outer retina, as well as the retinal pigment epithelium (RPE), were graded based on OCT images. RESULTS: Reading performance, measured as maximum reading speed, was associated with specific retinal biomarkers. The disruption of the ellipsoid zone (EZ) in the parafoveal region and the presence of disorganization of the inner retinal layers (DRIL) in the parafovea were correlated with reduced reading speed. These associations were independent of the presence of intraretinal or subretinal fluid. CONCLUSIONS: Understanding the relationship between retinal biomarkers and reading performance could contribute to a comprehensive evaluation of visual function and quality of life in patients with DME, leading to better management strategies and treatment outcomes.

Distinct Pathways of Macular Atrophy in Type 3 Macular Neovascularization Associated With AMD.

Purpose: To explore the occurrence of macular atrophy (MA) in eyes with age-related macular degeneration (AMD)-associated Type 3 macular neovascularization (MNV) treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Importantly, we aimed at describing the existence of separate pathways leading to MA. Methods: We analyzed 41 participants (41 eyes) with treatment-naïve Type 3 MNV who were followed up for a duration of 12 months after beginning the anti-VEGF therapy. At the one-year follow-up visit, optical coherence tomography (OCT) scans were reviewed for the presence of MA. MA regions of interest (ROIs) were selected and traced back to their original dominant baseline lesion (i.e., precursor) through previous serially captured OCT scans. Baseline lesions included precursors associated with the development and exudation of MNV and causes external to the neovascularization itself. Results: At the one-year follow-up visit, MA was graded to be present in 38 (92.7%) out of 41 eyes. These 78 MA ROIs were divided into two subgroups according to the precursor lesion, yielding a group of 53 MA lesions with precursors associated with the development and exudation of MNV (i.e., MA caused by physical harm from Type 3 neovessels, collapse of a serous pigment epithelium detachment, and fibrosis) and 25 MA regions with precursors external to the neovascularization itself (i.e., MA caused by drusen or subretinal drusenoid deposits). Conclusions: Eyes with Type 3 MNV are commonly complicated by MA and precursors of MA include causes associated with the development and exudation of MNV, as well as lesions unrelated to the neovascularization process itself.

Platelet rich plasma for primary macular hole: A case series.

OBJECTIVE: To evaluate the anatomical and functional macular results and rate of complications following surgical treatment of primary macular hole (MH) with autologous platelet rich plasma (a-PRP) use. DESIGN: retrospective, interventional, non-randomized case series. PARTECIPANTS AND METHODS: A cohort of 9 consecutive patients from January 1, 2019 to August 31, 2021 who underwent vitrectomy with a-PRP use for primary MH were included. Anatomical results based on spectral domain- optical coherence tomography (SD-OCT) and visual acuity were analyzed. RESULTS: 10 pseudophakic eye of 9 patients were enrolled. Six patients were female and three patients were male. The mean age was 69.9 years ± 1.48. The baseline MH minimum diameter was 486.1 µm ± 37.1, and mean pre operative best-corrected visual acuity (BCVA) was 0.91 ± 0.03 logMAR (Snellen equivalent 20/160). Mean 1 month post operative BCVA was 0.81 ± 0.57 logMAR (Snellen equivalent 20/130; p = 1.000); mean 3 month post operative BCVA was 0.66 ± 0.04 logMAR (Snellen equivalent 20/90; p = 0.006); mean 6 month post operative BCVA was 0.6 ± 0.04 logMAR (Snellen equivalent 20/80; p < 0.001). In all eyes, 10/10 (100%), there was a complete MH closure at 6 months follow up: 5 eyes (50%) with a U-type closure pattern, 4 eyes (40%) with a V-type pattern and 1 eye (10%) with an irregular foveal contour closure at 6 month follow-up. No ocular and systemic complications were reported. CONCLUSION: The a-PRP use is a successful and promising vitreoretinal surgical technique option for primary MH.

Validation of a deep learning model for automatic detection and quantification of five OCT critical retinal features associated with neovascular age-related macular degeneration.

PURPOSE: To develop and validate a deep learning model for the segmentation of five retinal biomarkers associated with neovascular age-related macular degeneration (nAMD). METHODS: 300 optical coherence tomography volumes from subject eyes with nAMD were collected. Images were manually segmented for the presence of five crucial nAMD features: intraretinal fluid, subretinal fluid, subretinal hyperreflective material, drusen/drusenoid pigment epithelium detachment (PED) and neovascular PED. A deep learning architecture based on a U-Net was trained to perform automatic segmentation of these retinal biomarkers and evaluated on the sequestered data. The main outcome measures were receiver operating characteristic curves for detection, summarised using the area under the curves (AUCs) both on a per slice and per volume basis, correlation score, enface topography overlap (reported as two-dimensional (2D) correlation score) and Dice coefficients. RESULTS: The model obtained a mean (±SD) AUC of 0.93 (±0.04) per slice and 0.88 (±0.07) per volume for fluid detection. The correlation score (R2) between automatic and manual segmentation obtained by the model resulted in a mean (±SD) of 0.89 (±0.05). The mean (±SD) 2D correlation score was 0.69 (±0.04). The mean (±SD) Dice score resulted in 0.61 (±0.10). CONCLUSIONS: We present a fully automated segmentation model for five features related to nAMD that performs at the level of experienced graders. The application of this model will open opportunities for the study of morphological changes and treatment efficacy in real-world settings. Furthermore, it can facilitate structured reporting in the clinic and reduce subjectivity in clinicians' assessments.

Pitchfork sign following pars Plana vitrectomy for idiopathic epiretinal membrane: A case report.

PURPOSE: To report a case of pitchfork sign following pars plana vitrectomy for idiopathic epiretinal membrane. STUDY DESIGN: Case report. RESULTS: A 75-year-old man was referred to the surgical retina service due to a quantitative and qualitative decline in vision in the left eye (LE) for several months. Optical coherence tomography (OCT) examination revealed the presence of a stage III epiretinal membrane (ERM) according to the Govetto classification. Seven days after undergoing a 25-gauge pars plana vitrectomy (PPV) with ERM peeling and balanced salt solution (BSS) tamponade, OCT examination revealed the presence of the 'pitchfork sign' in the macular region, along with the detection of a choroidal neovascularization (CNV) through OCT-A examination. After receiving two monthly intravitreal anti-VEGF injections, a complete regression of the MNV was observed. CONCLUSIONS: We reported, for the first time, the iatrogenic onset of the pitchfork sign following vitreoretinal surgery. This discovery highlights the unique presentation of the pitchfork sign in the context of surgical procedures, expanding our comprehension of its range of causes.

Relationship of Topographic Distribution of Macular Atrophy Secondary to Neovascular AMD and Reading Performance.

Purpose: The purpose of this study was to provide a topographical assessment of macular atrophy in successfully treated neovascular age-related macular degeneration (AMD) eyes to investigate determinants of monocular reading performance. Methods: A total of 60 participants (60 eyes) with previously treated neovascular AMD and absence of optical coherence tomography (OCT) signs of exudation were enrolled. Reading performance was assessed monocularly using Radner charts. The following variables were obtained: (i) the reading acuity was defined as the logarithm of the reading acuity determination (LogRAD), at the smallest sentence, a patient is able to read in less than 30 seconds; (ii) the maximum reading speed was defined as the fastest time achieved and is calculated in words per minute (wpm). OCT images were reviewed for the presence of macular atrophy within the central, 4 inner and 4 outer Early Treatment Diabetic Retinopathy Study (ETDRS) grid subfields. Contributory factors affecting reading performance were examined using univariable and multivariable linear mixed model considering reading acuity and reading speed as dependent variables. Results: Median (interquartile range [IQR]) values were 0.53 (IQR = 0.17) LogRAD for reading acuity, and 144 (60) wpm for maximum reading speed. Thirty-five out of 60 (58.3%) eyes were characterized by the presence of macular atrophy. In multiple regression analysis, reading acuity was significantly associated with presence of macular atrophy in the foveal central circle (P = 0.024). Conversely, the maximum reading speed was associated with presence of macular atrophy in the inner-right ETDRS subfield (P = 0.005). Conclusions: We showed a significant relationship between presence and location of macular atrophy and reading performance in neovascular AMD.

Platelet concentrates in macular hole surgery. A journey through the labyrinth of terminology, preparation, and application: a comprehensive review.

The surgical management of macular holes is undergoing continuous evolution, with recent focus on the utilization of platelet concentrates as a promising adjunctive intervention. Currently, they present a valid surgical approach for achieving anatomical and functional success with a non-inferiority comparably to the alternative surgical techniques. Nonetheless, the utilization of varied platelet concentrates terminologies, coupled with the lack of standardization in their preparation methodologies, engenders both lexical confusion and challenges in comparing scientific studies published up until now. In this review, we summarized the published evidence concerning the application of platelet concentrates in macular holes surgery, aiming to clarify the terminology and methodologies employed and to establish a common consensus facilitating further development and diffusion of this promising technique.

Ocular Surface Disease in Patients With Atopic Dermatitis Treated With Dupilumab: A Prospective Case-Control Study.

PURPOSE: The aim of this study was to evaluate the variation of dry eye disease (DED) prevalence in patients with atopic dermatitis (AD) treated with dupilumab. METHODS: This prospective case-control study included consecutive patients with moderate-to-severe AD scheduled for dupilumab between May and December 2021 and healthy subjects. DED prevalence, the Ocular Surface Disease Index, tear film breakup time test, osmolarity, Oxford staining score, and Schirmer test results were collected at baseline, 1 month, and 6 months after dupilumab therapy. The Eczema Area and Severity Index was assessed at baseline. Ocular side effects and discontinuation of dupilumab were also recorded. RESULTS: Seventy-two eyes from 36 patients with AD treated with dupilumab and 36 healthy controls were included. Prevalence of DED increased from 16.7% at baseline to 33.3% at 6 months in the dupilumab group ( P = 0.001), whereas it remained unchanged in the control group ( P = 0.110). At 6 months, the Ocular Surface Disease Index and Oxford score increased (from 8.5 ± 9.8 to 11.0 ± 13.0, P = 0.068, and from 0.1 ± 0.5 to 0.3 ± 0.6, P = 0.050, respectively), the tear film breakup time test and Schirmer test results decreased (from 7.8 ± 2.6 s to 7.1 ± 2.7 s, P < 0.001, and from 15.4 ± 9.6 mm to 13.2 ± 7.9 mm, P = 0.036, respectively) in the dupilumab group, whereas they remained stable in the control group ( P > 0.05). Osmolarity was unchanged (dupilumab P = 0.987 and controls P = 0.073). At 6 months after dupilumab therapy, 42% of patients had conjunctivitis, 36% blepharitis, and 2.8% keratitis. No severe side effects were reported, and none of the patients discontinued dupilumab. No association between Eczema Area and Severity Index and DED prevalence was shown. CONCLUSIONS: DED prevalence increased in patients with AD treated with dupilumab at 6 months. However, no severe ocular side effects were found and no patient discontinued therapy.

INTERSESSION REPEATABILITY OF READING PERFORMANCE MEASURES IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To assess the intersession repeatability of reading performance measures in patients with previously treated neovascular age-related macular degeneration and good best-corrected visual acuity (≥20/40 Snellen). METHODS: Ninety-one patients (91 eyes) with a diagnosis of previously treated neovascular age-related macular degeneration and good best-corrected visual acuity (≥20/40 Snellen) were prospectively enrolled. Reading performance metrics were assessed using Radner charts, and these measurements were repeated after 7 days to obtain the intersession repeatability. To test repeatability, we calculated the intraclass correlation coefficient, the 95% coefficient of repeatability, and the coefficient of variation for each reading parameter: 1) reading acuity (RA-LogRAD); 2) maximal reading speed-words per minute; 3) RA score (RA score-LogRAD); and 4) critical print size-LogRAD. RESULTS: Mean ± standard deviation best-corrected visual acuity was 0.13 ± 0.01 logMAR [range: 0.00-0.30 logMAR]. The intraclass correlation coefficient values indicated a good reliability for all the analyzed metrics (0.901 for RA; 0.859 for max reading speed; 0.906 for RA score; and 0.868 for critical print size). The coefficient of repeatability was 0.2 LogRAD for RA, 63.2 words per minute for max reading speed, 0.2 LogRAD for RA score, and 0.2 LogRAD for critical print size. Coefficient of variation was 5.5% for RA, 8.9% for max reading speed, 5.8% for RA score, and 6.9% for critical print size. CONCLUSION: Reading performance metrics are characterized by good values of intersession repeatability in patients with neovascular age-related macular degeneration with good best-corrected visual acuity. Our findings may grant the employment of such measures in trials assessing the visual outcome in these patients.

Macula-Off Retinal Detachment with Refractory Macular Hole Previously Closed with Autologous Platelet-Rich Plasma: A Case Report.

The purpose of this report was to present a case of a refractory full-thickness macular hole (FTMH) complicated with recurrent retinal detachment (RD) previously treated with an autologous platelet-rich plasma (aPRP) plug. A 65-year-old male patient presented to our department with a FTMH, RD, and a giant retinal break. Preoperative best corrected visual acuity (BCVA) was 1.40 logMAR (20/500). A 25-G pars plana vitrectomy (PPV) was performed, with peripheral retinal-breaks laser barrage, peeling of the internal limiting membrane, and silicon oil injection. One month later, spectral domain optical coherence tomography (SD-OCT) showed the persistence of the FTMH with a diameter of 712 µm. Therefore, the patient underwent silicon oil removal and aPRP injection with good anatomical outcome and improvement of BCVA to 0.6 log-MAR (20/80). Two months later a recurrence of macula-off RD was detected, but SD-OCT showed that the aPRP plug was still in place and kept the two margins of the macular hole together. The patient underwent a further PPV with silicon oil injection and subsequent silicon oil removal with no postoperative complications. Two months later, the retina remained attached, SD-OCT confirmed FTMH closure and BCVA was 0.52 logMAR (20/63). In conclusion, this case report aims to underline the remarkable efficacy of aPRP in promoting FTMH closure, which was maintained despite subsequent recurrence of macula-off RD.

Relaxing Retinotomy in Recurrent and Refractory Full-Thickness Macular Holes: The State of the Art.

The prevailing standard of care for primary repair of full-thickness macular holes (FTMHs) is pars plana vitrectomy with internal limiting membrane (ILM) peeling and gas tamponade, as it gives a high closure rate of roughly 90%. On the other hand, the surgical management of recurrent and refractory FTMHs represents, so far, a demanding and debated subject in vitreoretinal surgery since various approaches have been proposed, with no consensus concerning both adequate selection criteria and the best surgical approach. In addition, the existence of multiple case series/interventional studies showing comparable results and the lack of studies with a direct comparison of multiple surgical techniques may lead to uncertainty. We present an organized overview of relaxing retinotomy technique, a surgical approach available nowadays for the secondary repair of recurrent and refractory FTMHs. Besides the history and the description of the various techniques to perform relaxing retinotomies, we underline the results and the evidence available to promote the use of this surgical approach.

Retinal Thickness Deviation: A New OCT Parameter for Assessing Diabetic Macular Edema.

(1) Purpose: To determine the "retinal thickness deviation" (RTD) in diabetic macular edema (DME) eyes treated with intravitreal therapy and to establish associations between RTD and best-corrected visual acuity (BCVA). (2) Methods: We conducted a retrospective study, including consecutive patients with DME eyes undergoing intravitreal therapy with two years of follow-up. BCVA and central subfield thickness (CST) were collected at baseline and at 12 months and 24 months of follow-up. RTD was calculated as the absolute difference between measured and normative CST values at each time point. Linear regression analyses were performed between RTD and BCVA and between CST and BCVA. (3) Results: One hundred and four eyes were included in the analysis. The RTD was 177.0 (117.2) µm at baseline, 97.0 (99.7) µm at 12 months and 89.9 (75.3) µm at 24 months of follow-up (p < 0.001). RTD showed a moderate association with BCVA at baseline (R2 = 0.134, p < 0.001) and 12 months (R2 = 0.197, p < 0.001) and a substantial association at 24 months (R2 = 0.272, p < 0.001). The CST showed a moderate association with BCVA at baseline (R2 = 0.132, p < 0.001) and 12 months (R2 = 0.136, p < 0.001), while the association was weak at 24 months (R2 = 0.065, p = 0.009). (4) Conclusions: RTD showed a good association with visual outcome in patients with DME eyes undergoing intravitreal treatment.

The Short-Term Results of Autologous Platelet-Rich Plasma as an Adjuvant to Re-Intervention in the Treatment of Refractory Full-Thickness Macular Holes.

The purpose of this study was to investigate the short-term efficacy and safety of autologous platelet-rich plasma (a-PRP) as an adjuvant to revisional vitrectomy for refractory full-thickness macular holes (rFTMHs). We conducted a prospective, non-randomized interventional study including patients with rFTMH after a pars plana vitrectomy (PPV) with internal limiting membrane peeling and gas tamponade. We included 28 eyes from 27 patients with rFTMHs: 12 rFTMHs in highly myopic eyes (axial length greater than 26.5 mm or a refractive error greater than -6D or both); 12 large rFTMHs (minimum hole width > 400 µm); and 4 rFTMHs secondary to the optic disc pit. All patients underwent 25-G PPV with a-PRP, a median time of 3.5 ± 1.8 months after the primary repair. At the six-month follow-up, the overall rFTMH closure rate was 92.9%, distributed as follows: 11 out of 12 eyes (91.7%) in the highly myopic group, 11 out of 12 eyes (91.7%) in the large rFTMH group, and 4 out of 4 eyes (100%) in the optic disc pit group. Median best-corrected visual acuity significantly improved in all groups, in particular from 1.00 (interquartile range: 0.85 to 1.30) to 0.70 (0.40 to 0.85) LogMAR in the highly myopic group (p = 0.016), from 0.90 (0.70 to 1.49) to 0.40 (0.35 to 0.70) LogMAR in the large rFTMH group (p = 0.005), and from 0.90 (0.75 to 1.00) to 0.50 (0.28 to 0.65) LogMAR in the optic disc pit group. No intraoperative or postoperative complications were reported. In conclusion, a-PRP can be an effective adjuvant to PPV in the management of rFTMHs.

CONVENTIONAL INTERNAL LIMITING MEMBRANE PEELING VERSUS INVERTED FLAP FOR SMALL-TO-MEDIUM IDIOPATHIC MACULAR HOLE: A Randomized Trial.

PURPOSE: To compare conventional internal limiting membrane (ILM) peeling versus inverted flap technique in small-to-medium idiopathic macular hole. METHODS: Eyes with ≤400 µ m idiopathic macular holes were randomized into the conventional ILM peeling group (25 eyes) and inverted flap group (25 eyes). A 12-month follow-up was considered. Macular sensitivity (MS) change detected with MP-1 microperimetry was the primary outcome. Secondary outcomes included best-corrected visual acuity change, closure rate, anatomical findings on optical coherence tomography such as U-shape foveal contour, restoration of external limiting membrane, and ellipsoid zone. RESULTS: In both groups, MS improved throughout the follow-up. Final MS was greater in the conventional ILM peeling group compared with the inverted flap group, being 16.6 ± 2.3 dB versus 14.9 ± 2.9 dB, respectively ( P = 0.026). In both groups best-corrected visual acuity improved throughout the follow-up, with a final best-corrected visual acuity of 0.19 ± 0.14 logMar (20/31 Snellen) in the conventional ILM group and 0.22 ± 0.11 logMar (20/33 Snellen) in the inverted flap group ( P = 0.398). Anatomical hole closure was achieved in all cases. No difference in optical coherence tomography findings was shown between the two groups. CONCLUSION: A better final MS was found in eyes undergoing conventional ILM peeling. Inverted flap technique has disadvantages compared with conventional peeling for the treatment of small-to-medium idiopathic macular holes.

Reintervention rate in glaucoma filtering surgery: A systematic review and meta-analysis.

PURPOSE: Reintervention rate is an important factor impacting on patients, surgeons, and society. To date, only a few studies have focused on this topic. For this reason, a systematic review and meta-analysis was undertaken to assess the reintervention rate after glaucoma filtering surgery. MATERIALS AND METHODS: Prospective studies reporting the reintervention rate after glaucoma filtering surgery and with at least 12 months of follow-up were systematically searched on PubMed, Medline and Embase databases. The primary outcome was the total reintervention rate following surgery. Secondary outcomes were: the rate of manipulation, in-clinic and in-operating room reintervention; the reintervention rate for intraocular pressure (IOP) control and for complications; demographic, clinical and surgical variables associated with reintervention rate. RESULTS: Ninety-three studies with a total of 8345 eyes were eligible. The total reintervention rate was 1.84 (95% CI 1.57-2.13), with a lower rate for Baerveldt (0.53, 95% CI 0.29-0.83) and Preserflo (0.60, 95% CI 0.15-1.29), and a higher rate for Xen (4.26, 95% CI 2.59-6.31). The manipulation rate was 0.99 (95% CI 0.77-1.23), the in-clinic reintervention rate was 0.08 (95% CI 0.05-0.12) and the in-operating room reintervention rate was 0.28 (95% CI 0.22-0.35). The reintervention rate for IOP control was 1.26 (95% CI 1.04-1.51) and the reintervention rate for complications was 0.27 (95% CI 0.21-0.35). CONCLUSIONS: All types of surgery presented a total reintervention rate similar to the overall findings, except studies on Baerveldt and Preserflo Microshunt, with a lower rate, and Xen, with a higher rate. None of the variables evaluated were found to be directly associated with the explored outcomes.

Frequency of Intravitreal Anti-VEGF Injections and Risk of Death: A Systematic Review with Meta-analysis.

TOPIC: To investigate whether an increasing number of intravitreal anti-VEGF injections is associated with a higher mortality risk. CLINICAL RELEVANCE: The issue of systemic safety of intravitreal anti-VEGF therapy has been long discussed. Evidence from meta-analyses of randomized studies has shown no increased risk of mortality in the overall population, whereas some warning signals of higher mortality were found in patients with diabetes exposed to intense and prolonged treatment. Concerns have been raised about whether an increasing number of anti-VEGF injections could be associated with a higher mortality. METHODS: Randomized clinical trials enrolling arms with different intensities of anti-VEGF therapy were searched. The primary outcome measure was the incidence rate ratio (IRR) of death with 95% confidence interval (CI) for receiving 5 injections. The relationship between the number of injections and all-cause mortality was investigated. Separate regression analyses were conducted to investigate this relationship in subgroups of studies with different diseases and drugs. RESULTS: Fifty-two trials were included. Overall mortality rates of 1.02% and 3.36% were recorded at 12 and 24 months, respectively. Univariate regression showed that a larger number of injections was not associated with a significant increase in mortality both at 12 months (IRR, 1.16; 95% CI, 0.87-1.53; P = 0.31) and at 24 months (IRR, 1.05; 95% CI, 0.95-1.15; P = 0.34). According to subgroup analyses, in diabetic macular edema (DME) studies, a higher risk was marginally associated with an increasing number of injections at 24 months (IRR, 1.17; 95% CI, 1.02-1.33; P = 0.03). CONCLUSION: No significant influence of anti-VEGF treatment intensity on mortality was shown, supporting a message of reassurance over safety concerns of this therapy. Marginal evidence of a higher risk associated with a more intense treatment was found in patients with DME.