Behind the mask: a critical perspective on the ethical, moral, and legal implications of AI in ophthalmology.

PURPOSE: This narrative review aims to provide an overview of the dangers, controversial aspects, and implications of artificial intelligence (AI) use in ophthalmology and other medical-related fields. METHODS: We conducted a decade-long comprehensive search (January 2013-May 2023) of both academic and grey literature, focusing on the application of AI in ophthalmology and healthcare. This search included key web-based academic databases, non-traditional sources, and targeted searches of specific organizations and institutions. We reviewed and selected documents for relevance to AI, healthcare, ethics, and guidelines, aiming for a critical analysis of ethical, moral, and legal implications of AI in healthcare. RESULTS: Six main issues were identified, analyzed, and discussed. These include bias and clinical safety, cybersecurity, health data and AI algorithm ownership, the "black-box" problem, medical liability, and the risk of widening inequality in healthcare. CONCLUSION: Solutions to address these issues include collecting high-quality data of the target population, incorporating stronger security measures, using explainable AI algorithms and ensemble methods, and making AI-based solutions accessible to everyone. With careful oversight and regulation, AI-based systems can be used to supplement physician decision-making and improve patient care and outcomes.

Submacular hemorrhage during neovascular age-related macular degeneration: a meta-analysis and meta-regression on the use of tPA and anti-VEGFs.

BACKGROUND: Submacular hemorrhage (SMH) associated with neovascular age-related macular degeneration (nAMD) precipitates rapid visual decline and impacts quality of life. Treatments vary, but combined recombinant tissue plasminogen activator (tPA) and anti-vascular endothelial growth factor (anti-VEGF) therapy has gained prominence as a viable treatment option. OBJECTIVES: This study aims to evaluate the efficacy of the combination of tPA and anti-VEGF. METHODS: We conducted a systematic review meta-analysis following PRISMA guidelines, focusing on studies examining tPA and anti-VEGF therapy in SMH secondary to nAMD. Outcomes measured were change in best-corrected visual acuity (BCVA) and success rate of SMH displacement. Meta-regression assessed the relative efficacy of intravitreal and subretinal delivery. RESULTS: Out of 257 initial reports, 22 studies involving 29 patient populations met inclusion criteria. Our analysis showed significant improvement in BCVA and a high rate of successful SMH displacement with combined tPA and anti-VEGF therapy. No significant differences were found between subretinal and intravitreal tPA administration. Furthermore, when evaluating the effects of subretinal versus intravitreal anti-VEGF administration in patients treated with subretinal tPA, the results indicated similar efficacy. CONCLUSIONS: Combined tPA and anti-VEGF therapy is effective in managing SMH in nAMD patients, significantly improving visual acuity and SMH displacement. The location of tPA and anti-VEGF delivery did not significantly impact outcomes.

The ideal intravitreal injection setting: office, ambulatory surgery room or operating theatre? A narrative review and international survey.

PURPOSE: This study reviews evidence and provides recommendations for the ideal setting of intravitreal injection (IVI) administration of vascular endothelial growth factor (VEGF) inhibitors. METHODS: A multi-step approach was employed, including content analysis of regulations and guidelines, a systematic literature review, and an international survey assessing perioperative complications and endophthalmitis incidence in relation to injection settings. The literature review searched PubMed and Cochrane databases from 2006 to 2022, focusing on studies reporting correlations between complications and treatment settings. The survey utilized a web-based questionnaire distributed to clinical sites and the international ophthalmic community, with data managed using electronic capture tools. RESULTS: We reviewed regulations and guidelines from 23 countries across five continents, finding significant variation in IVI administration settings. In most countries, IVI is primarily administered in outpatient clean rooms (96%) or offices (39%), while in others, it is restricted to ambulatory surgery rooms or hospital-based operating theatres (4%). The literature review found that endophthalmitis risk after IVI is generally low (0.01% to 0.26% per procedure), with no significant difference between office-based and operating room settings. The international survey (20 centers, 96,624 anti-VEGF injections) found low overall incidences of severe perioperative systemic adverse events and endophthalmitis, independent of injection settings. CONCLUSION: No significant differences in perioperative complications were observed among various settings, including operating theatres, ambulatory surgery rooms, offices, hospitals, or extra-hospital environments. Choosing the appropriate clinical setting can optimize patient management, potentially increasing effectiveness, quality, productivity, and capacity.

Effects of Antithrombotic Agents on Ophthalmological Outcomes, Cardiovascular Risk, and Mortality in Hypertensive Patients with Retinal Vein Occlusion: An Exploratory Retrospective Study.

Background and objectives: Because few data are available, the aim of this study is to analyze the effects of antithrombotic agents (ATAs) on visual function and long-term risk of cardiovascular events and mortality in hypertensive patients with retinal vein occlusion (RVO). Materials and methods: Hypertensive patients with RVO were consecutively selected from 2008 to 2012 and followed for a median of 8.7 years. Ophthalmologists evaluated and treated RVO complications, and best-corrected visual acuity (BCVA) was checked at each visit during the first one year of follow-up. Survival analysis was conducted on the rate of the composite endpoint of all-cause deaths or non-fatal cardiovascular events. Results: Retrospectively, we collected data from 80 patients (age 68 ± 12 years, 39 males). Central and branch RVO was present in 41 and 39 patients, respectively, and 56 patients started ATAs (50 antiplatelet drugs, 6 warfarin, and 2 low-molecular weight heparin). Average BCVA of the cohort did not change significantly during one-year of follow-up. The only predictor of BCVA was the baseline BCVA value. There was a reduction in proportion and severity of macular edema and an increase in the cumulative proportion of retinal vein patency reestablishment during the follow-up, independent of treatment. ATAs had no effects on one-year BCVA, intraocular complications, or the composite endpoint rate. Conclusions: In this exploratory study, ATAs had no effect on BCVA during the first one year of follow-up and on the composite endpoint during the long-term follow-up. Further prospective studies need to be conducted with an accurate standardization of the intraocular and antithrombotic treatment to define the positive or negative role of ATAs in hypertensive patients with RVO.

Automated diabetic retinopathy detection with two different retinal imaging devices using artificial intelligence: a comparison study.

PURPOSE: In this study, we evaluated the diagnostic performance of an automated artificial intelligence-based diabetic retinopathy (DR) algorithm with two retinal imaging systems using two different technologies: a conventional flash fundus camera and a white LED confocal scanner. METHODS: On the same day, patients underwent dilated colour fundus photography using both a conventional flash fundus camera (TRC-NW8, Topcon Corporation, Tokyo, Japan) and a fully automated white LED confocal scanner (Eidon, Centervue, Padova, Italy). All images were analysed for DR severity both by retina specialists and the AI software EyeArt (Eyenuk Inc., Los Angeles, CA) and graded as referable DR (RDR) or not RDR. Sensitivity, specificity and the area under the curve (AUC) were computed. RESULTS: A series of 165 diabetic subjects (330 eyes) were enrolled. The automated algorithm achieved 90.8% sensitivity with 75.3% specificity on images acquired with the conventional fundus camera and 94.1% sensitivity with 86.8% specificity on images obtained from the white LED confocal scanner. The difference between AUC was 0.0737 (p = 0.0023). CONCLUSION: The automated image analysis software is well suited to work with different imaging technologies. It achieved a better diagnostic performance when the white LED confocal scanner is used. Further evaluation in the context of screening campaigns is needed.

Current role of intravitreal injections in Irvine Gass syndrome-CRIIG study.

OBJECTIVE: To analyze the role of intravitreal anti-vascular endothelial growth factor (anti-VEGF) or steroid injection for the management of Irvine Gass syndrome. METHODS: It is an interventional, retrospective, multicenter study. One hundred and thirty-two injections were given in 79 eyes of 72 patients with Irvine Gass syndrome. Patients were treated with at least one intravitreal injection of either anti-VEGF or steroid. Outcomes were measured at 12 months (± 1 week). [Ranibizumab (Lucentis; Genentech, South San Francisco, CA) (Razumab; Intas Pharmaceutical Ltd, Ahmedabad, India) Bevacizumab (Avastin; Genentech, South San Francisco, CA) or Aflibercept (Eylea; Regeneron, Tarrytown, NY)] or steroids [Dexamethasone implant (Ozurdex, Allergan Inc, Irvine, CA) or intravitreal triamcinolone)]. RESULTS: Intravitreal injections were initiated in (67.6%) of eyes within 14 weeks of diagnosis. Intravitreal dexamethasone implant was used as the initial intravitreal therapy in (73.4%) of eyes. More than fifty percent (54.5%) of the patients were switched from anti-VEGF to Intravitreal dexamethasone implant. Reduction in the mean CMT was 336.7 ± 191.7 and 160.1 ± 153.1 microns in eyes treated within four weeks and more than 14 weeks from diagnosis (p = 0.005). Mean ETDRS letter gain was 16.7 ± 12.9 and 5.2 ± 9.2 in eyes treated within 4 weeks and more than 14 weeks from diagnosis (p = 0.004). Three eyes injected with intravitreal dexamethasone implant reported an intraocular pressure spike of > 25 mmHg which was controlled with topical medications. No other ocular or systemic adverse events were observed. CONCLUSION: Study results suggest that physicians tend to introduce intravitreal therapy within 14 weeks of diagnosis. The most common therapy at initiation and for the switch is intravitreal dexamethasone implant. Patients treated early (within 4 weeks) respond better in terms of structure and function.

TWELVE-MONTH OUTCOMES OF INTRAVITREAL AFLIBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Fixed Versus As-needed Dosing.

PURPOSE: To compare the clinical outcomes of aflibercept used with a fixed schedule with a pro-re-nata (PRN) retreatment regimen in patients affected by neovascular age-related macular degeneration. METHODS: This is a prospective multicenter, noninferiority, propensity score-matched study evaluating the 12-month outcomes of aflibercept given either according to labeling or following a PRN regimen. Patients included in the latter group received one initial injection, followed by monthly visits and as-needed retreatment. RESULTS: One-to-one matching resulted in fixed and PRN arms containing 92 eyes each. Visual acuity improved from baseline to 12 months in both the study groups. At Month 4, the fixed regimen was equivalent to the PRN regimen (mean difference: 1.75 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: -1.42 to +4.92). The pro-re-nata regimen failed to show noninferiority compared with the fixed regimen at both Month 8 (mean difference: 3.43 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: +0.25 to +6.22) and Month 12 (mean difference: 4.83 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: +1.37 to +8.29). All patients in the fixed group received seven injections. Patients included in the PRN arm received a mean of 5.5 ± 1.6 treatments. CONCLUSIONS: Aflibercept given with a fixed treatment regimen produces better visual acuity outcomes than an individualized regimen.

A comparison between a white LED confocal imaging system and a conventional flash fundus camera using chromaticity analysis.

BACKGROUND: Conventional flash fundus cameras capture color images that are oversaturated in the red channel and washed out in the green and blue channels, resulting in a retinal picture that often looks flat and reddish. A white LED confocal device was recently introduced to provide a high-quality retinal image with enhanced color fidelity. In this study, we aimed to evaluate the color rendering properties of the white LED confocal system and compare them to those of a conventional flash fundus camera through chromaticity analysis. METHODS: A white LED confocal device (Eidon, Centervue, Padova, Italy) and a traditional flash fundus camera (TRC-NW8, Topcon Corporation, Tokyo, Japan) were used to capture fundus images. Color images were evaluated with respect to chromaticity. Analysis was performed according to the image color signature. The color signature of an image was defined as the distribution of its pixels in the rgb chromaticity space. The descriptors used for the analysis are the average and variability of the barycenter positions, the average of the variability and the number of unique colors (NUC) of all signatures. RESULTS: Two hundred thirty-three color photographs were acquired with each retinal camera. The images acquired by the confocal white LED device demonstrated an average barycenter position (rgb = [0.448, 0.328, 0.224]) closer to the center of the chromaticity space, while the conventional fundus camera provides images with a clear shift toward red at the expense of the blue and green channels (rgb = [0.574, 0.278, 0.148] (p < 0.001). The variability of the barycenter positions was higher in the white LED confocal system than in the conventional fundus camera. The average variability of the distributions was higher (0.003 ± 0.007, p < 0.001) in the Eidon images compared to the Topcon camera, indicating a greater richness of color. The NUC percentage was higher for the white LED confocal device than for the conventional flash fundus camera (0.071% versus 0.025%, p < 0.001). CONCLUSIONS: Eidon provides more-balanced color images, with a wider richness of color content, compared to a conventional flash fundus camera. The overall higher chromaticity of Eidon may provide benefits in terms of discriminative power and diagnostic accuracy.

Early Effects of Dexamethasone Implant on Macular Morphology and Visual Function in Patients with Diabetic Macular Edema.

PURPOSE: To evaluate the early effects of dexamethasone implant in patients with diabetic macular edema (DME). METHODS: Eyes with DME were prospectively included in the study. Best-corrected visual acuity (BCVA) measurement, complete ophthalmic evaluation, and spectral-domain optical coherence tomography were performed at baseline and 1, 2, 3, 7, 14, 21, 28, 60, and 90 days after treatment. RESULTS: Twenty-three eyes of 20 patients were included in the study. Mean central retinal thickness (CRT) decreased rapidly after treatment (p < 0.0001, repeated measures ANOVA) from 511 µm at baseline to 469 µm after 1 day (p < 0.05), and 275 µm (p < 0.01) at the end of the follow-up. BCVA gain (p < 0.0001, repeated measures ANOVA) was on average +2 ETDRS letters at day 1 (not significant), +9 letters from day 28 to day 90 (p < 0.01). CONCLUSION: Intravitreal dexamethasone implant showed an early and fast effect in reducing CRT and improving BCVA in DME patients.

Intravitreal bevacizumab for choroidal neovascularization due to pathologic myopia: long-term outcomes.

PURPOSE: To report the long-term results of anti-vascular endothelial growth factor (VEGF) therapy for choroidal neovascularization (CNV) secondary to pathological myopia (PM). METHODS: Prospective interventional study with extension phase. Eyes affected by CNV due to PM included. All patients received an intravitreal bevacizumab injection (1.25 mg/0.05 ml) at baseline. Re-treatment was considered at each follow-up visit. RESULTS: The study included 101 consecutive eyes of 86 patients. All patients reached 24 months of follow-up. After 24 months, mean best-corrected visual acuity (BCVA) improvement was -0.13 (95 % CI: -0.2; -0.05) logMAR (p < 0.001) and central retinal thickness (CRT) decreased on average by 67 (95 % CI: 27; 102) µm (p < 0.01). The chorioretinal atrophy (CRA) area increased significantly after 2 years of follow-up (+7.82 mm(2), p < 0.0001). Patients received 4.1 treatments, on average. Thirty-two eyes were included in the extension phase (from 24 to 60 months of follow-up). Visual acuity improved on average by -0.05 (95 % CI: -0.2; 0.1) logMAR (p > 0.05) compared to baseline. Mean reduction in CRT was 102 (95 % CI: 64;141) µm (p < 0.01). The CRA area enlarged significantly after 5 years of follow-up (+14.15 mm(2), p < 0.0001). Patients received a mean of 6.7 treatments in 60 months. CONCLUSIONS: An individualized regimen with intravitreal bevacizumab to treat CNV secondary to PM resulted in BCVA improvement and CRT decrease at 2 and 5 years. The main visual benefit was obtained between month 3 and month 24. A gradual loss of the initial BCVA gain was observed starting from month 30 to month 60 due to progression of CRA.

INTRAVITREAL AFLIBERCEPT FOR CHOROIDAL NEOVASCULARIZATION DUE TO AGE-RELATED MACULAR DEGENERATION UNRESPONSIVE TO RANIBIZUMAB THERAPY.

PURPOSE: To assess the efficacy of intravitreal injection of aflibercept for treating choroidal neovascularization due to age-related macular degeneration unresponsive to ranibizumab. METHODS: Prospective noncomparative study. Indication for conversion to aflibercept (2.0 mg) was a failed response to ranibizumab, defined as persistent or recurrent subretinal and/or intraretinal fluid on spectral domain optical coherence tomography. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score), fluorescein angiography, indocyanine green angiography, and spectral domain optical coherence tomography were performed at baseline. Patients were followed up monthly, and retreatment was considered at physician discretion based on functional and morphological patterns. RESULTS: Ninety-two eyes were included in the study. At 12 months, mean best-corrected visual acuity (±SD) change was +1.8 (±10.3), Early Treatment Diabetic Retinopathy Study letters and central retinal thickness (±SD) decreased on average by 112 (±173) µm. Patients received a mean of 3.5 ± 1.8 injections. No significant adverse event was observed during the follow-up. CONCLUSION: A low number of intravitreal aflibercept injections reversed the preswitching trend toward losing vision and produced stable visual acuity and morphological improvements for up to 12 months in patients with neovascular age-related macular degeneration, not responding to ranibizumab.

Early effects of dexamethasone implant on macular morphology and visual function in patients with macular edema secondary to retinal vein occlusion.

PURPOSE: To evaluate the early effects of the intravitreal erodible dexamethasone implant Ozurdex in patients with macular edema due to retinal vein occlusion (RVO). METHODS: Eyes with macular edema due to RVO were prospectively included in the study and received a 700-µg dexamethasone implant. Best-corrected visual acuity (BCVA) measurement, complete ophthalmic evaluation and spectral-domain optical coherence tomography were performed at baseline and 1, 2, 3, 7, 14, 21, 28, 60, and 90 days after treatment. RESULTS: Nineteen eyes of 18 patients were included in the study. Mean central retinal thickness (CRT) decreased rapidly after treatment (p < 0.0001) from 503 µm at baseline to 288 µm after 1 day and 199 µm at the end of the follow-up. BCVA gained on average +6 ETDRS letters after 1 day and +11 letters at day 90 (p = 0.0001). CONCLUSION: The intravitreal dexamethasone implant showed a fast effect in reducing CRT and improving BCVA in RVO patients.

Functional and morphological changes after macular pucker surgery: an optical coherence tomography and microperimetric study.

PURPOSE: To investigate the relationship among functional and morphological findings before and after macular pucker surgery. METHODS: Thirty-eight eyes with idiopathic macular pucker that underwent 25-gauge vitrectomy and infracyanine green-assisted internal limiting membrane peeling were prospectively enrolled. Main outcome measures were best-corrected visual acuity (BCVA), spectral-domain optical coherence tomography findings and MP-1 microperimetry findings. RESULTS: Mean BCVA improvement was 0.34 logMAR (p < 0.0001). Mean central retinal thickness (CRT) reduction was 50 µm (p = 0.0041). Mean retinal sensitivity improvement was 0.9. Patients with a greater improvement of postoperative BCVA showed worse baseline BCVA (p < 0.001), shorter final inner/outer segment (IS/OS) interruption length (p = 0.039) and thinner final CRT (p = 0.035). Furthermore, final BCVA was correlated with baseline IS/OS interruption length (p = 0.001). CONCLUSION: Baseline BCVA, CRT and IS/OS integrity can be used to predict the functional outcomes after macular pucker surgery.

Intravitreal steroids for the treatment of retinal diseases.

Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events.

Management of treatment-naïve diabetic macular edema patients: Review of real-world clinical data.

The high prevalence of Diabetic macular edema (DME) is a real global health problem. Its complex pathophysiology involves different pathways. Over the last decade, the introduction of intravitreal treatments has dramatically changed the management and prognosis of DME. Among the different treatment options, inhibitors of vascular endothelial growth factor (anti-VEGF) and intravitreal steroids implants represent the first-line therapy of DME. We conducted a review of electronic databases to compile the available evidence about the clinical management of DME in a clinical setting, with a special focus on treatment-naïve patients. Anti-VEGF therapies represent a valuable option for treating DME patients. However, many patients do not respond properly to this treatment and, due to its administration regimen, many patients receive suboptimal treatment in real life. Current evidence demonstrated that in patients with DME, DEX-i improved significantly both anatomic and visual outcomes. Besides eyes with insufficient anti-VEGF respond or recalcitrant DME cases, DEX-i can be effectively and safely used in treatment-naïve DME patients as first line therapy. DEX-i may be considered first line therapy in different clinical scenarios, such as DME eyes with a greater inflammatory component, patients with cardiovascular events, vitrectomized eyes, or those requiring cataract surgery. In conclusion, there are still many points for improvement pending in the clinical management of the patient with DME. Since DME treatment must follow a patient-tailored approach, selecting the best therapeutic approach for each patient requires a good understanding of the pathophysiology of DME.

Multimodal imaging in diabetic retinopathy and macular edema: An update about biomarkers.

Diabetic macular edema (DME), defined as retinal thickening near, or involving the fovea caused by fluid accumulation in the retina, can lead to vision impairment and blindness in patients with diabetes. Current knowledge of retina anatomy and function and DME pathophysiology has taken great advantage of the availability of several techniques for visualizing the retina. Combining these techniques in a multimodal imaging approach to DME is recommended to improve diagnosis and to guide treatment decisions. We review the recent literature about the following retinal imaging technologies: optical coherence tomography (OCT), OCT angiography (OCTA), wide-field and ultrawide-field techniques applied to fundus photography, fluorescein angiography, and OCTA. The emphasis will be on characteristic DME features identified by these imaging technologies and their potential or established role as diagnostic, prognostic, or predictive biomarkers. The role of artificial intelligence in the assessment and interpretation of retina images is also discussed.

Effects of VEGF inhibition on retinal morphology, neovascular network size, and visual acuity in patients with vascularized pigment epithelium detachment because of occult choroidal neovascularization.

PURPOSE: To report the results of vascular endothelial growth factor inhibition for vascularized pigment epithelium detachment associated with choroidal neovascularization secondary to age-related macular degeneration. METHODS: We performed a retrospective analysis of patients affected by vascularized pigment epithelium detachment treated with intravitreal anti-vascular endothelial growth factor (0.5 mg of ranibizumab or 1 mg of bevacizumab) and a follow-up of 12 months. Retinal angiomatous proliferations were excluded. Treatment was conducted with an initial loading phase followed by a pro re nata phase. Fluorescein angiography and indocyanine green angiography were performed at baseline and every 3 months. RESULTS: Forty eyes were included in this study. After a follow-up of 12 months and 5.5 treatments on average, best-corrected visual acuity did not vary significantly. Central retinal thickness and pigment epithelium detachment height were significantly reduced, whereas the choroidal neovascularization area remained constant. CONCLUSION: In vascularized pigment epithelium detachment, anti-vascular endothelial growth factor therapy shows visual stabilization but not best-corrected visual acuity gain. However, it is associated with significant morphologic improvements, and it may offer a benefit over the natural course of the disease.

Triple therapy for anti-vascular endothelial growth factor nonresponders in neovascular age-related macular degeneration: impact of different photodynamic therapy parameters.

PURPOSE: To evaluate the safety and exploratory efficacy of triple therapy (TT) with single-session intravitreal ranibizumab, modified juxtascleral triamcinolone, and photodynamic therapy (PDT) in exudative age-related macular degeneration non-responder to anti-vascular endothelial growth factor. METHODS: Thirty consecutive eyes were included. The first 10 eyes (cohort 1) enrolled received same-day TT with reduced-fluence/reduced-irradiance PDT, 10 eyes (cohort 2) received same-day TT with reduced-fluence/standard irradiance PDT, the last 10 eyes (cohort 3) received same-day TT with standard fluence/standard irradiance PDT. RESULTS: All patients completed the 6-month follow-up. Mean best corrected visual acuity (BCVA) at baseline was 1.1 (cohort 1), 0.9 (cohort 2) and 1.1 (cohort 3) logMAR. After 6 months, mean BCVA change was -0.15 (not significant), -0.13 (not significant) and 0.29 (p < 0.05) logMAR, respectively. Among eyes treated with standard fluence/standard irradiance PDT, 2 showed choroidal ischemia. CONCLUSIONS: The combination of modified juxtascleral triamcinolone, reduced-fluence PDT, and ranibizumab appears as a safe treatment option.

Intravitreal injections: a healthcare failure modes and effects analysis.

PURPOSE: To perform a risk mitigation review of intravitreal injections. METHODS: A pan-European expert team conducted a healthcare failure modes and effects analysis (HFMEA) of intravitreal injection techniques. Possible failures at each stage were identified and potential causes and effects considered. A risk value (1-10) was assigned for each failure's severity, probability of occurrence and likelihood of going undetected, and a risk priority number (RPN) calculated. RESULTS: This HFMEA revealed 91 intravitreal injection failure modes, of which 28, deemed to have an appreciable risk, were explored. Recommendations were proposed to reduce these risks, mostly relating to patient, staff, room and equipment preparation, injection procedure and patient discharge. CONCLUSIONS: The HFMEA process produced practical recommendations to improve the risk profile of intravitreal injection.

Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose.

BACKGROUND: The effects of various dosages and treatment regimens on intravitreal aflibercept concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF were evaluated using a drug and disease assessment model. The 8 mg dosage received specific attention. METHODS: A time-dependent mathematical model was developed and implemented using Wolfram Mathematica software v12.0. This model was used to obtain drug concentrations after multiple doses of different aflibercept dosages (0.5 mg, 2 mg, and 8 mg) and to estimate the time-dependent intravitreal free VEGF percentage levels. A series of fixed treatment regimens were modeled and evaluated as potential clinical applications. RESULTS: The simulation results indicate that 8 mg aflibercept administered at a range of treatment intervals (between 12 and 15 weeks) would allow for the proportion of free VEGF to remain below threshold levels. Our analysis indicates that these protocols maintain the ratio of free VEGF below 0.001%. CONCLUSIONS: Fixed q12-q15 (every 12-15 weeks) 8 mg aflibercept regimens can produce adequate intravitreal VEGF inhibition.