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Gabriel Katz,1,2,* Fidaa el Zhalka,3,* Ronel Veksler,1 Anfisa Ayalon,3 Elad Moisseiev2,3 1Department of Ophthalmology, Sheba Medical Center, Ramat Gan, Israel; 2Sackler School of Medicine, TelAviv University, TelAviv, Israel; 3Department of Ophthalmology, Meir Medical Center, Kfar Saba, Israel*These authors contributed equally to this workCorrespondence: Elad MoisseievDepartment of Ophthalmology, Meir Medical Center, 59 Tshernichovsky St., Kfar Saba, 4428164, IsraelTel +97297471527Fax +97297472427Email elad_moi@netvision.net.ilPurpose: To investigate the effect of phacovitrectomy on the post-operative anterior chamber depth (ACD) and refractive outcomes, and to analyze the potential differences between vitreous filling with BSS, air and gas.Methods: Patients who underwent phacovitrectomy were included in this study and invited for repeated post-operative examination including refraction and biometry at least 3 months after the surgery. Data retrieved included demographic information, indication for phacovitrectomy, surgical details, type of vitreous filling (BSS, air or gas), pre-operative and post-operative biometric data including K-readings, axial length (AL), and ACD, as well as spherical equivalent (SE) values of the target and final refraction.Results: Forty-three eyes of 43 patients were included in this study, including 10 eyes filled with BSS, 18 with air and 15 with gas. The mean difference between the final measured spherical equivalent (SE) and the SE of the intended target refraction was 0.61± 0.68 D (p = 0.019). Only 58.1% of eyes had a final SE within ± 0.5D of the target refraction. Following surgery, AL remained unchanged, while mean pre-operative ACD increased significantly from 3.11± 0.34 mm to 4.77± 0.47 mm (p < 0.001). There was no difference in refractive error between the vitreous fillings and no correlation with AL or ACD.Conclusions: Phacovitrectomy is associated with lower accuracy of post-operative refraction compared to cataract surgery. This may be attributed to a significant change in ACD, influencing the effective lens position of the IOL, and may require adjustment of the pre-operative calculations.Keywords: anterior chamber depth, ACD, phacovitrectomy, refractive error, tamponade

PurposeTo evaluate the safety and efficacy of finasteride treatment in patients with central serous chorioretinopathy (CSC).MethodsRetrospective review of 29 eyes of 23 patients who were treated with finasteride for CSC. Previous medical and ocular history, steroid use, length of finasteride treatment, additional treatments for CSC, visual acuity (VA), central macular thickness (CMT), and presence of subretinal fluid (SRF) throughout the follow-up period, and the occurrence of any complications were recorded.ResultsInitial VA was 0.29±0.31 logMAR, and a trend towards improved VA was noted after 3 months (0.25±0.36 logMAR; P=0.07). VA was significantly improved at the final follow-up (0.23±0.27 logMAR; P=0.024). Initial CMT was 354±160 μm, and was significantly reduced after 1 month of treatment (284±77 μm; P=0.002) and this was maintained to the end of follow-up (247±85 μm; P=0.001). A significant reduction in SRF presence was found at all time points, with an overall 75.9% rate of complete resolution. Following discontinuation, SRF recurrence was noted in 37.5% of cases. No adverse events were recorded.ConclusionsFinasteride is a safe and effective treatment for CSC. It may be a possible new option for the initial management of patient with CSC, and a suggested treatment approach is presented.

Eytan Nov,1 Elad Moisseiev1,2 1Department of Ophthalmology, Meir Medical Center, Kfar Saba, Israel; 2Sackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelCorrespondence: Elad Moisseiev Department of OphthalmologyMeir Medical Center, 59 Tshernichovsky Street, Kfar Saba 4428164, IsraelTel +97297471527Fax +97297472427Email elad_moi@netvision.net.ilPurpose: To analyze the top 100 most-cited papers on pars intravitreal injections.Methods: Literature search using the bibliographic databases of the ISI Web of Knowledge for all types of publications on intravitreal injections published between 1965 and 2019 in peer-reviewed journals.Results: Eighty-three of the top 100 papers on intravitreal injections were published in ophthalmology journals, their majority in the top five Q1 leading journals in the field. They originated from 16 different countries, predominantly from the USA (n=52), and were all published in English. These manuscripts cover a wide spectrum of topics but were mostly focused on retinal diseases (n=60) and the use of anti-VEGF or steroid agents (n=75).Discussion: This bibliographic study provides a unique perspective on the evolution and assimilation of intravitreal injections, from their introduction, through their present role as the most common therapeutic procedure in ophthalmology, to future developments.Keywords: bibliography, citation, historical, intravitreal injection

Elad Moisseiev,1–3 Anat Loewenstein,2,3 Glenn Yiu1 1UC Davis Eye Center, University of California Davis, Sacramento, CA, USA; 2Ophthalmology Department, Tel Aviv Medical Center, Tel Aviv, 3Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract: Recent advances have made it possible to image the suprachoroidal space, and the understanding of its clinical applications is currently being greatly expanded. This opinion piece covers the advances in imaging techniques that enable the demonstration of the suprachoroidal space, and its implication in various retinal pathologies. It also reviews its potential uses as a route for drug delivery for the treatment of retinal diseases, and its use in innovative surgical techniques. Current research is leading the way for the suprachoroidal space to be an aspect of retinal disease diagnosis, monitoring, medical treatment, and surgical manipulation. Keywords: suprachoroidal space, enhanced depth imaging, drug delivery, potential space

Elad Moisseiev, Shimon Kurtz, Moshe Lazar, Gabi ShemeshDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelBackground: The purpose of this study was to evaluate the safety and efficacy of a fixed combination of timolol maleate 0.5% + brimonidine tartrate 0.2% (Combigan®) for reduction for intraocular pressure (IOP) in patients with glaucoma when the dose frequency is increased from twice to three times daily.Methods: The patients included had either primary open angle glaucoma or ocular hypertension. Those who were previously on treatment completed a drug washout period prior to inclusion. IOP was measured at baseline, after 4 weeks of treatment with Combigan twice daily, and again after a further 4 weeks of Combigan three times daily. Blood pressure, heart rate, and oxygen saturation were also recorded at each assessment.Results: Thirty-one eyes from 31 patients were included. Increasing the Combigan dose frequency resulted in a statistically significant (P < 0.001) additional reduction in IOP of 2.25 ± 1.18 mmHg, corresponding to a further 10.3% reduction in IOP from baseline. No local or systemic adverse effects were documented.Conclusion: Treatment with Combigan three times daily was more effective in reducing IOP than the twice-daily regimen, with no increase in adverse effects.Keywords: Combigan®, timolol, brimonidine, glaucoma, dose frequency

Naomi Fischer, Elad Moisseiev, Michael Waisbourd, Michaella Goldstein, Anat Loewenstein Department of Ophthalmology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Purpose: The study reported here investigated the rates of systemic serious adverse events (SAEs) following treatment with intravitreal bevacizumab for age-related macular degeneration (AMD) in comparison with a matched control group. Methods: A retrospective age- and sex-matched case-control design was used. Data were collected using patient charts and telephone surveys. The main outcome measure was difference in number of hospital admissions between the two groups. Hospitalizations were further analyzed according to whether or not they were due to arteriothrombotic SAEs. Results: Each group comprised 65 participants. There were significantly more hospital admissions among bevacizumab-treated patients than in the control group (P = 0.039). Sub-analysis of hospitalizations due to arteriothrombotic causes did not reveal a statistically significant difference between groups (P = 0.629). Conclusion: The results suggest that intravitreal bevacizumab is not associated with an increased risk of arteriothrombotic SAEs. Its widespread use for the treatment of AMD appears to be systemically safe. Keywords: Avastin®, serious adverse events, safety

Elad Moisseiev,1,3 Tzahi Sela,2 Liza Minkev,2 David Varssano1,31Department of Ophthalmology, Tel-Aviv Medical Center, Tel-Aviv, Israel; 2Care Vision, Tel Aviv, Israel; 3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelPurpose: To evaluate the trends in corneal refractive procedure selection for the correction of myopia, focusing on the relative proportions of laser in situ keratomileusis (LASIK) and surface ablation procedures.Methods: Only eyes that underwent LASIK or surface ablation for the correction of myopia between 2008–2011 were included in this retrospective study. Additional recorded parameters included patient age, preoperative manifest refraction, corneal thickness, and calculated residual corneal bed thickness. A risk score was given to each eye, based on these parameters, according to the Ectasia Risk Factor Score System (ERFSS), without the preoperative corneal topography.Results: This study included 16,163 eyes, of which 38.4% underwent LASIK and 61.6% underwent surface ablation. The risk score correlated with procedure selection, with LASIK being preferred in eyes with a score of 0 and surface ablation in eyes with a score of 2 or higher. When controlling for age, preoperative manifest refraction, corneal thickness, and all parameters, the relative proportion of surface ablation compared with LASIK was found to have grown significantly during the study period.Conclusions: Our results indicate that with time, surface ablation tended to be performed more often than LASIK for the correction of myopia in our cohort. Increased awareness of risk factors and preoperative risk assessment tools, such as the ERFSS, have shifted the current practice of refractive surgery from LASIK towards surface ablation despite the former's advantages, especially in cases in which the risk for ectasia is more than minimal (risk score 2 and higher).Keywords: surface ablation, LASIK, PRK, myopia correction, ectasia

Gabi Shemesh*, Elad Moisseiev*, Moshe Lazar1, Shimon Kurtz Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel*The first two authors contributed equallyPurpose: To evaluate the safety and efficacy in intraocular pressure (IOP) reduction of increasing Cosopt dosage from twice to three times a day.Methods: The study included patients with primary open-angle glaucoma or ocular hypertension. After a washout period, IOP was measured at baseline, after 4 weeks of treatment with Cosopt twice a day, and after another 4 weeks of treatment with Cosopt three times a day. Blood pressure, heart rate, and oxygen saturation levels were also recorded.Results: Twenty-nine eyes of 29 patients were included. Increasing Cosopt dosage resulted in a statistically significant (P < 0.001) additional reduction in IOP of 2.2 ± 1.58 mmHg (10.69% ± 7.49% of the baseline IOP values). There were no local or systemic adverse effects.Conclusion: Treatment with Cosopt three times a day was more effective in reducing IOP than twice a day, with no effect on safety.Keywords: Cosopt, timolol, dorzolamide, glaucoma, intraocular pressure, dosage

PurposeTo evaluate the long-term visual prognosis and complications of patients who received intravitreal Ozurdex injections for the treatment of macular edema (ME) due to retinal vein occlusion (RVO).MethodsA total of 17 patients who received Ozurdex injections in our institution as part of the GENEVA study were recalled for examination. Recorded parameters included final visual acuity (VA), final retinal thickness by optical coherence tomography, persistence of ME, and the occurrence of any complications.ResultsMean follow-up time was 50.5 months. Patients with branch RVO (BRVO) had a more favorable prognosis than central RVO (CRVO), and their mean VA had improved significantly, whereas the mean VA for the patients with CRVO did not improve significantly. Retinal thickness had reduced significantly in the whole group and in each subgroup separately. Complications included 10 patients with cataract progression, 1 with elevated intraocular pressure, and 1 with neovascularization and vitreous hemorrhage.ConclusionsThis is the first reported long-term evaluation of patients treated with Ozurdex. Our results indicate that it has favorable long-term safety profile, and may have a beneficial effect on the visual prognosis in BRVO even in the absence of continuous treatment. Further research is required to establish the optimal retreatment schedule for Ozurdex. [ABSTRACT FROM AUTHOR]

Introduction: Eyelid blepharoplasty, including lower eyelid blepharoplasty, are among the most common aesthetic surgeries recently performed. In contrast to upper eyelid blepharoplasty, lower eyelid blepharoplasty is a surgery with mostly an aesthetic indication, in which patients bear all associated costs, and their expectations rise accordingly. Nevertheless, the complexity of the anatomy, the differences in the aging processes of the face and eyelids between patients, the diversity of surgical methods, and the expectations gap make the surgery more challenging in comparison to upper eyelid blepharoplasty. A comprehensive understanding of the eyelid anatomy and the surrounding tissues, as well as matching expectations alongside with thorough preoperative evaluation, are all essential for providing a more personal adjustment of the surgical method and avoiding complications and mental distress for both patients and surgeons. This article briefly reviews the anatomy and aging processes of the lower eyelids, the main surgical approaches, and their common complications. Moreover, we present a framework for how such complications can be avoided.

Introduction: Ophthalmology is a broad branch of medicine, which includes an extensive range of sub-specialties on one hand, and interfaces with other fields of medicine on the other. This issue contains papers from different sub-specialties of ophthalmology, that together cover several of the most important issues in this field. These papers present the topics in a manner compatible with the wide readership of the journal, and touch upon the most current updates and innovations. The original articles in this issue deal with treatments for the prevention of myopia progression in children, treatment of complicated cases of retinal detachment in children, ocular manifestations of vascular abnormalities in patients with coronavirus, and a series of patients with corneal damage due to ultraviolet-C (UVC) lamps intended to clear the air of this virus. The review papers describe glaucoma and the current change in its treatment paradigm, which focuses on earlier intervention, ocular manifestations of systemic autoimmune diseases, and the possibilities for artificial corneal implantation. We hope that this special issue will be of interest and clinical value to its readers.

Purpose: To compare the efficacy of two different topical non-steroidal anti-inflammatory drugs (NSAIDs) drops with versus without conservatives after intravitreal injections (IVIs)., Design: Prospective, randomized, placebo-controlled, single-blinded comparative study., Participants and Method: A total of 308 eyes of 252 patients receiving an IVI of anti-vascular endothelial growth factor (anti-VEGF) were randomly assigned to receive either a single drop of nepafenac 0.1%, preservative-free diclofenac 0.1%, or artificial tears (control group) immediately after IVI. Primary outcome measure was pain scores immediately, six hours and twenty-four hours post- injection., Results: 166 patients received one topical drop of NSAIDS, of which 90 in the diclofenac group and 76 in the nepafenac group. Additional 86 patients were included in the control group. Mean reported pain score was significantly lower at six hours after IVI in the preservative-free diclofenac group (17.1 ± 23.0) than in the nepafenac group (26.2 ± 31.9) and the control group (27.5 ± 29.2) (p = 0.03). At twenty-four hours post-injection there was no statistically significant difference between the groups. Patients reported less pain compared to previous IVIs and none referred to urgent health care, but these findings were not statistically significant., Conclusions: The use of topical preservative-free NSAIDs may be superior to preservative- containing NSAIDs in pain relief after IVIs and may be considered as part of the treatment protocol of this population.

Aim: To analyze the top 100 most cited papers related to amblyopia., Methods: A bibliographic search in the Institute for Scientific Information Web of Knowledge across 55 years was performed., Results: Eighty-nine of the 100 papers were published in first-quartile journals. Half (50) of the senior authors were from the USA. Most papers dealt with clinical science (72) and included original research (84). Forty-two of the articles related to all three types of amblyopia (refractive, strabismic and deprivation). Thirty-four related to both strabismic and refractive amblyopia. Around two-thirds of the papers dealt with treatment (34) and pathophysiology (30). Almost a quarter (23%) of the papers were multicenter studies. Nearly half (48) of the papers were published between 2000 and 2010. The Pediatric Eye Disease Investigator Group (PEDIG) published the highest number of studies (11), which dealt more with treatment (p = 0.01) and had higher average number of citations per years (p = 0.05). A larger number of articles on the treatment of amblyopia are newer (p = 0.01). There was no correlation between the time of their publication and the number of citations (p = 0.68, r = 0.042)., Conclusions: Half of the papers were published between 2000 and 2010 and were spearheaded by PEDIG. Most papers dealt with treatment and pathophysiology. This study provides an important historical perspective, emphasizing the need for additional research to better understand this preventable and curable childhood vision impairment., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To evaluate the effect of syringe design and filling technique on the accuracy of anti-vascular endothelial growth factor delivery., Methods: Volume output was measured with three syringe designs: a 1.0-mL slip-tip syringe, a 1.0-mL Luer-lock syringe, and a ranibizumab prefilled syringe-using two filling techniques ("upward" and "downward") and two fluids (water and bevacizumab). A total of 300 simulated injections were performed. Accuracy was determined by difference from the intended volume of 50 µ L and by mean absolute percentage error., Results: Volume outputs were significantly different between syringe designs, with mean values of 61.99 ± 4.18 µ L with the 1-mL slip-tip syringe, 57.43 ± 4.95 µ L with the Luer-lock 1-mL syringe, and 51.06 ± 4.74 µ L with the ranibizumab syringe, making the latter the most accurate syringe. There were 37 cases (12.3%) of underdosing below 50 µ L, the majority of which occurred with the ranibizumab syringe. The "downward" technique reduced the occurrence of air bubbles., Conclusion: Intravitreal injections using 1.0-mL syringes are less accurate than using the ranibizumab prefilled syringe, which has a low-volume and low dead-space plunger design. The variability in volume output may result in less predictable treatment response, especially in cases of underdosing, which were more common with the ranibizumab syringe.

Background: Timely management of aphakic children is critical for the rehabilitation of adequate visual gain. This study aims to evaluate the long-term efficacy of scleral contact lenses in terms of visual outcomes, complications, and compliance in aphakic children., Methods: Retrospective data review of children with congenital or acquired cataract, or subluxated crystalline lenses, who underwent lensectomy from 2004 to 2018 and who used scleral contact lenses for refractive correction. Collected data from the follow up period included recorded aphakic refraction and visual acuity, complications following scleral contact lens wear documented in the clinic and ophthalmic emergency room and compliance to lens wear according to parental feedback on every visit in the clinic., Results: 76% of cases, with final best corrected visual acuity (BCVA) of 20/40 or better achieved in seventeen eyes (34%). The rate of amblyopia was 50%. Strabismus developed in 56% of children, and those had less favourable visual outcomes (0.43 ± 0.4 LogMAR without strabismus and 0.8 ± 0.5 LogMAR with strabismus, p = 0.015). No corneal infections were documented during the follow up. Main adverse effect on the ocular surface was superficial punctate keratopathy (n = 16). Compliance was good in 48 children (96%)- except for two cases, the scleral lenses were tolerated well by all children., Conclusion: Scleral contact lenses are an effective means of visual rehabilitation in aphakic children after lensectomy and may be used long-term with good compliance of wear, excellent visual outcomes, and tolerable adverse events., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To investigate the features and treatment response in Caucasian patients with polypoidal choroidal vasculopathy (PCV), initially treated with bevacizumab., Methods: 45 eyes of 43 treatment-naïve patients with PCV were included in this retrospective study, all uniformly initially treated with three bevacizumab injections monthly. OCT characteristics and clinical parameters were recorded and analyzed at presentation, after the initial 3 bevacizumab injections and at the final follow up period., Results: Following 3 monthly bevacizumab injections visual acuity significantly improved with a mean gain of one line of vision. Central macular thickness (CMT) significantly improved from a mean of 402.1 ± 130.8 μm at presentation to 322.0 ± 96.8 μm (p < 0.01). Subretinal fluid, intraretinal fluid and submacular hemorrhage significantly improved. 53% were later switched to aflibercept and showed better response in the central macular thickness in comparison to those in which bevacizumab injections were continued. No correlation was found between the presence of pachyvessels or increased choroidal thickness and the improvement in VA or CMT., Conclusion: Fixed first-line treatment with intravitreal bevacizumab monotherapy in non-Asian PCV patients achieves satisfactory visual and anatomical outcomes., (© 2022. The Author(s).)

Purpose: To find the best cost-effective neovascular age-related macular degeneration (nAMD) treatment to improve vision while avoiding complications. The model is based on a cost-risk tradeoff analysis from policymakers' perspective., Design: A powerful and flexible simulation modeled outcomes of 2 years of treatment with the 4 commonly used anti-vascular endothelial growth factor drugs (bevacizumab, ranibizumab, aflibercept, and brolucizumab) across 3 injection protocols, building on prior findings that these drugs are noninferior. The model incorporates blinding complications, their management, and associated costs to society. Each option and several what-if scenarios were simulated 1,000 times with 100,000 hypothetical patients., Participants: One hundred thousand simulated patients using data from published clinical trials., Method: Case- and eye-specific cost-risk economic analysis., Main Outcome Measures: Costs of nAMD treatment per patient and number of eyes that become blind as a result of treatment over 2 years., Results: Using published prices and fees, the injection protocol that follows published clinical studies, results showed that the mean±standard deviation cost per patient were $16,859 ± $3.65, $32,949 ± $3.27, $39,831 ± $3.80, and $53,056 ± $2.99 for bevacizumab, brolucizumab, aflibercept, and ranibizumab, respectively. The numbers±standard deviations of treated eyes that became blind were 108 ± 10.18, 694 ± 26.66, 168 ± 12.83, and 108 ± 10.52, respectively. We further provide a lower bound (when all patients are maximally extended) and upper bound (when no patient is extended) to these numbers. For brolucizumab, the upper bound is the 2-month interval injection protocol., Conclusions: Taking a policymaking perspective, this study suggested that bevacizumab is the preferred first-line therapy. Recommendation for second-line therapy depends on the extent of the policymaker's risk aversion because of the tradeoff between cost and risk of blindness as a result of treatment. If risk neutral, the least expensive option (brolucizumab) is preferred. But if policymakers are moderately to highly risk averse, then aflibercept or ranibizumab are preferred. Because medical advances and different costs may change our findings, we provide a free application (https://eye-inj.shinyapps.io/calc/) for readers who wish to use different cost structures. Simulating outcomes is an innovative approach, unique in ophthalmology, and presents a significant opportunity because it can be adapted easily to different settings (using different costs, risks, and protocols) and to other diseases (e.g., diabetic macular edema), to ultimately improve wide-scale decision-making and use of funds., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The 100 most cited papers on retinal detachment (RD) were analysed using a bibliographic study. The bibliographic databases of the ISI Web of Knowledge were searched, limited to research articles published between 1965 and 2020 in peer-reviewed journals. The papers were ranked in order of number of citations since publication. Ninety of the 100 most cited papers on RD were published in 12 ophthalmology journals, with 74 of them published in American Journal of Ophthalmology (n=31), Ophthalmology (n=23), Archives of Ophthalmology (n=10) and Investigative Ophthalmology and Visual Science (n=10); the remaining 10 papers were published in 8 journals from other fields of medical research. All papers in the top 100 were published in English. The 100 most cited papers on RD originated from 12 different countries, with the majority (72 papers) originating from the USA. The 100 identified papers represent a mix of clinical trials and animal/laboratory studies. This bibliographic study provides a unique perspective and insight into some of the most influential contributions in RD understanding and management over the last 55 years., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aimed to identify baseline optical coherence tomography (OCT) factors in branch retinal vein occlusion (BRVO) that predict response to bevacizumab injections., Methods: It is a retrospective case series of consecutive patients that underwent OCT at diagnosis, and the central macular thickness (CMT), extent of disorganized retinal inner layers, and outer retinal layers including external limiting membrane, ellipsoid zone (EZ), and cone outer segment tips (COST) were measured. Patients received 3 consecutive monthly injections of bevacizumab followed by pro re nata treatment. The main outcome measure was improvement in best-corrected visual acuity (BCVA) after 1 year. Results are expressed as mean ± SD, and p value <0.05 was considered statistically significant., Results: Overall, 66 eyes of 66 patients, with an average age of 68.5 ± 11.4 years, were included. The mean BCVA improved significantly from 0.68 logMAR at baseline to 0.50 logMAR at 1 year (p < 0.001). Baseline logMAR BCVA (r = 0.41, p < 0.001) and CMT (r = 0.23, p = 0.04) were associated with improvement while EZ (r = -0.24, p = 0.05) and COST (r = -0.32, p = 0.01) disruption with deterioration in BCVA., Conclusion: In patients with naïve BRVO treated with bevacizumab, BCVA improvement at 1 year can be predicted from baseline BCVA, CMT, extent of COST disruption, and EZ disruption., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Purpose: The aim of the study was to investigate the correlation between optical coherence tomography (OCT) findings and visual acuity outcomes after treatment with intravitreal bevacizumab (IVB) injections for age-related macular degeneration (AMD) patients with peripapillary choroidal neovascularization (PPCNV)., Methods: The study involved a retrospective case series of consecutive patients diagnosed with PPCNV secondary to AMD. All patients were treated with IVB injections with a follow-up time of 1 year. Data collected included best-corrected visual acuity (BCVA) and automated and manually measured OCT parameters., Results: A total of 68 eyes were diagnosed with PPMV. Of them, 30 eyes of 30 patients aged 84.3 ± 6.9 years of which 63.3% female gender were included. Baseline BCVA was 0.46 ± 0.62 logMAR (Snellen 20/57), average choroidal thickness was 193.2 ± 22 μm, and mean number of IVB injections was 7.2 ± 1.9. After 1 year, BCVA was 0.56 ± 0.78 logMAR (Snellen 20/72) (p = 0.28). Eyes with greater central retinal thickness (r = -0.36, p = 0.05), greater subretinal hyper-reflective material (SHRM) area (r = -0.37, p = 0.05), and greater sub-retinal fluid (SRF) area (r = -0.73, p < 0.001) had a significantly smaller improvement in BCVA. Eyes with pigment epithelium detachment (PED) (0.68 ± 0.90 vs. 0.21 ± 0.12, p = 0.03) had a significantly worse BCVA., Conclusions: Our data suggest that AMD-related PPCNV with greater foveal thickness, PED size, SHRM, and SRF areas have worse final BCVA prognosis., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Purpose: This study aimed to compare the risk for post-injection endophthalmitis between different anti-vascular endothelial growth factor (VEGF) agents and syringe preparation techniques., Methods: A retrospective study of anti-VEGF injections performed in 3 large ophthalmology departments between 2013 and 2019 was conducted. Injections were categorized according to the drug and the syringe-filling technique - prefilling by a hospital pharmacy, prefilling by a good manufacturing practice (GMP) pharmacy, self-drawing from the vial by the injecting physician, and use of a prefilled syringe. Cases of endophthalmitis were identified, and their rates were analyzed., Results: A total of 197,402 injections were included, and 53 cases of endophthalmitis were identified (0.027% risk). The risk of endophthalmitis following injections with syringes that were prefilled by GMP pharmacies or the manufacturers was significantly lower than that following injections which were self-drawn by the physician (0.019% vs. 0.055%, p < 0.0001). For ranibizumab, risk of endophthalmitis decreased since it became available in a prefilled syringe (0.054% vs. 0.014%, p = 0.066), bordering on statistical significance., Conclusions: The syringe-filling technique is an important factor determining risk of post-injection endophthalmitis. Use of GMP-grade prefilling by professional pharmacies or the manufacturers significantly reduces this risk and should be the technique of choice for all drugs administered by intravitreal injection., (© 2021 S. Karger AG, Basel.)

Purpose: To evaluate the prevalence of residual air bubbles following intravitreal injections of anti-VEGF agents, and to compare two techniques designed to reduce their occurrence., Methods: Patients who received intravitreal injections reported the presence of air bubbles following the procedure, and were followed to determine when they disappeared. Two techniques used to reduce air bubbles prior to injection were compared-tapping the syringe with the needle up ("upwards" technique) or down ("downwards" technique). Rates of residual air bubbles were compared between techniques, and between different drugs., Results: The study included 344 intravitreal injections, 172 injected with each technique. The overall rate of residual air bubbles was 11.3%, with 94.9% resolution by 48 h. The rate was significantly lower with the "downwards" technique (7.5% vs. 15.1%, p = 0.027). It was also significantly lower with ranibizumab injected using pre-filled syringes than with bevacizumab and aflibercept (0% vs. 12.1% and 14.7%, p < 0.0001). A questionnaire revealed patients reported medium levels of discomfort and a high importance of avoiding air bubbles., Conclusions: Residual air bubbles are a common occurrence, likely to be experienced by most patients undergoing repeated injections. This phenomenon may be significantly reduced by using the described "downwards" technique, or pre-filled syringes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We analyze the detectability of intraorbital foreign bodies (OrbFBs) of various types and sizes using computed tomography (CT) and magnetic resonance imaging using a three-Tesla machine (MRI 3 T)., Methods: An ex vivo model of sheep eyes with preserved extraocular muscles and orbital fat tissue placed in the orbital cavity of the human skull was created for this study. Foreign bodies made of four different materials - plastic, bottle glass, stone and wood - each in three different sizes (large, intermediate and small) were inserted into the soft tissue of the orbit in the extraocular space. Each orbit was scanned by CT and MRI. Images were analyzed by a senior radiologist and underwent masked review by three oculoplastic surgeons., Results: Analysis of MRI and CT scans identified distinguishing characteristics for each of the four materials. This information was further integrated into a clinical algorithm. CT allowed easier identification of most of the embedded materials compared to MRI. Smaller OrbFB size was associated with lower detectability. Review of CT yielded 94.4% agreement between oculoplastic specialists in detecting OrbFbs using CT scans and allowed detection of most OrbFBs. In contrast, the overall agreement with MRI was lower: 66.7% with T1 MPRAGE, 50% with T1TSE, 88.9% with T2 TSE and 72.2% with T2 TSE FS. Plastic was the most difficult material to detect in all size categories., Conclusions: CT offers a clear advantage over MRI for detecting and localizing nonmetallic OrbFBs of all sizes, except for plastic. Plastic OrbFBs can be detected with CT depending on size but are more visible in MRI scans.

Purpose: To describe optical coherence tomography characteristics of full-thickness macular holes (FTMHs) in age-related macular degeneration patients., Methods: A multicenter, retrospective, observational case series of patients diagnosed with age-related macular degeneration and FTMHs seen between January 1, 2009, and January 3, 2020. Clinical charts and spectral-domain optical coherence tomography images were reviewed. Optical coherence tomography findings included FTMH-inverted trapezoid or hourglass appearance, central macular thickness (CMT), complete retinal pigment epithelium and complete retinal outer retinal atrophy, and presence of pigment epithelium detachment and epiretinal membrane. The mean outcome was the morphologic and functional characterization of different subtypes of FTMHs., Results: A total of 86 eyes of 85 consecutive patients, with mean age of 80.31 ± 8.06 and mean best-corrected visual acuity of 1.17 ± 0.58 logarithm of the minimal angle of resolution. Two different subtypes of FTMHs were identified: tractional and degenerative. Fifty (58%) degenerative FTMHs characterized with inverted trapezoid appearance and 36 (42%) tractional FTMHs characterized with hourglass appearance. Degenerative FTMHs presented with 66% of CMT < 240 µm, 14% of CMT > 320, and 70% of complete retinal outer retinal atrophy, in comparison with 41% of CMT < 240 µm, 42.9% of CMT > 320%, and 20% of complete retinal outer retinal atrophy in the tractional FTMH group (P = 0.002, 0.003, <0.001, respectively). The presence of epiretinal membrane and pigment epithelium detachment where significantly higher in tractional FTMHs (P = 0.02, 0.03, respectively)., Conclusion: Degenerative and tractional FTMHs may be two distinct clinical entities. Discerning degenerative from tractional FTMHs is possible by using optical coherence tomography features including shape of the FTMHs, CMT, internal-external ratio of FTMHs, and presence of complete retinal outer retinal atrophy, pigment epithelium detachment, and epiretinal membrane.

Purpose: To describe the mechanisms and outcomes of open globe injuries (OGIs) in patients 70 years or older., Methods: A retrospective chart review of patients from two large academic centers in Israel who were underwent surgery for OGI. Data was collected from surgical and clinic charts. Anatomical and functional results were recorded as well any additional surgeries and complications., Results: Thirty-two eyes of 32 patients were included. The mechanism of OGI consisted of blunt trauma with ocular rupture secondary to falls. All eyes underwent immediate primary closure of the corneal and scleral lacerations. Additional surgeries were performed in 34.3% of cases. In 31.2% of cases additional surgery was not required, and in 21.9% of cases the damage was so devastating that additional procedures were not recommended. Four patients (12.5%) chose not to undergo additional surgery. Mean visual acuity at presentation was 2.24 ± 0.72 logMAR and it improved to 1.92 ± 0.89 logMAR at final follow-up ( p  = 0.002). VA at presentation was significantly correlated to final VA ( p  < 0.001)., Conclusions: OGI in the elderly represents a unique group. It is mostly related to falls, with a female predominance and a poor visual prognosis. In this patient population, general health concerns and increased risks of anesthesia require special attention. Care should be taken to educate elderly patients and their caretakers on how to avoid falls.

The 100 most-cited papers on age-related macular degeneration (AMD) were analysed using a bibliographic study. The bibliographic databases of the Institute for Scientific Information Web of Knowledge were searched, limited to research articles published between 1965 and 2020 in peer-reviewed journals. The papers were ranked in order of number of citations since publication. Five of the top 10 (and 3 of the top 4) papers reported randomised clinical trial results for either anti-vascular endothelial growth factor agents or nutritional supplements. Four of the top 10 papers reported genotype-phenotype associations between AMD and variants in Complement Factor H . This bibliographic study provides perspective and insight into many of the most influential contributions in the understanding and management of AMD and its evolution over time., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: The authors report no conflicts of interest in this communication.

The suprachoroidal space (SCS), a potential space between the sclera and choroid, is becoming an applicable method to deliver therapeutics to the back of the eye. In recent years, a vast amount of research in the field has been carried out, with new discoveries in different areas of interest, such as imaging, drug delivery methods, pharmacokinetics, pharmacotherapies in preclinical and clinical trials and advanced therapies. The SCS can be visualized via advanced techniques of optical coherence tomography (OCT) in eyes with different pathologies, and even in healthy eyes. Drugs can be delivered easily and safely via hollow microneedles fitted to the length of the approximate thickness of the sclera. SCS injections were found to reach greater baseline concentrations in the target layers compared to intravitreal (IVT) injection, while agent clearance was faster with highly aqueous soluble molecules. Clinical trials with SCS injection of triamcinolone acetonide (TA) were executed with promising findings for patients with noninfectious uveitis (NIU), NIU implicated with macular edema and diabetic macular edema (DME). Gene therapy is evolving rapidly with viral and non-viral vectors that were found to be safe and efficient in preclinical trials. Here, we review these novel different aspects and new developments in clinical treatment of the posterior segment of the eye.

Prcis: Our study shows that iStent implant does not cause significant image artifacts, heating, or displacement during magnetic resonance imaging (MRI) scan. This device can be safely used in patients undergoing MRI scans using 3 Tesla (3T) machines., Purpose: The iStent is a medical grade titanium implant commonly implanted in the anterior chamber angle of glaucomatous eyes in order to reduce intraocular pressure and medication burden. As many people now have these devices implanted in their eyes, the issue of their compatibility with MRI in terms of safety and interference with interpretation of these studies commonly arises. The purpose of this study is to evaluate the safety of 3T MRI scans in eyes that have undergone iStent implantation and to assess the interference of the implant to the scan interpretation., Materials and Methods: An ex vivo model of sheep eye with an iStent and proximately placed heat detector probe was used to study changes in the temperature during MRI 3T scan. The study included 2 fresh eyes with preserved extraocular muscles and orbital fat tissue placed in the orbital cavity of a human skull. Each eye with orbital content was scanned with a 3T MRI machine., Results: No displacement of the implant was observed during MRI scanning. The heat detector showed mild temperature elevation during the first minutes of the scan from 14.6 to 16.5°C. The iStent was best visualized in T2 turbo spin echo sequences and showed no significant artifacts., Conclusion: iStent implants did not move during the MRI scan, showed minimal interaction with the magnetic field in terms of heating and image distortion. These interactions were not strong enough to present a substantial risk to patients with this implant undergoing an MRI scan., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the accuracy and agreement of optical coherence tomography angiography (OCTA) interpretation in cases of common retinal findings and diagnoses, and to evaluate the effect of OCT B-scans on OCTA interpretations., Methods: This is a case series consisting of a questionnaire with 8 cases demonstrating common retinal conditions of normal, age-related macular degeneration (AMD) and diabetic retinopathy (DR). Each case included OCTA images, and 58 participants were asked to identify retinal findings and provide a diagnosis. Following OCTA interpretation, the corresponding OCT B-scans were revealed and the participants were asked again to identify retinal findings and provide a diagnosis. The rates of accuracy and agreement for each condition were analyzed., Results: Overall the rates of accurate diagnosis and identification of retinal findings were 37.4 and 61.6%, respectively. Following addition of the OCT B-scans, the rates increased to 61.6 and 79.4%, respectively (p < 0.001 for both). A significant improvement in correct interpretation occurred in the normal and AMD cases, but not in the DR cases. There was no correlation with length of experience or self-reported familiarity with OCTA., Discussion: Considerable variability exists in OCTA interpretation, with mediocre rates of accuracy and agreement between clinicians. Increased familiarity as well as future automation advances will be needed to improve OCTA interpretation accuracy and uniformity., (© 2020 S. Karger AG, Basel.)

Neurodegeneration plays a significant role in the complex pathology of diabetic retinopathy. Evidence suggests the onset of neurodegeneration occurs early on in the disease, and so a greater understanding of the process is essential for prompt detection and targeted therapies. Neurodegeneration is a common pathway of assorted processes, including activation of inflammatory pathways, reduction of neuroprotective factors, DNA damage, and apoptosis. Oxidative stress and formation of advanced glycation end products amplify these processes and are elevated in the setting of hyperglycemia, hyperlipidemia, and glucose variability. These key pathophysiologic mechanisms are discussed, as well as diagnostic modalities and novel therapeutic avenues, with an emphasis on recent discoveries. The aim of this article is to highlight the crucial role of neurodegeneration in diabetic retinopathy and to review the molecular basis for this neuronal dysfunction, its diagnostic features, and the progress currently made in relevant therapeutic interventions., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Shani Pillar et al.)

Purpose: To compare the characteristics and response to treatment between patients with NVAMD presenting at the extremities of the AMD age spectrum., Methods: Fifty-four eyes of 47 patients were included in this retrospective study, divided by age at NVAMD presentation under 65 (n = 15) or over 85 (n = 39) years. All patients were initially treated with 3 monthly bevacizumab injections, followed by a PRN protocol. Clinical parameters and OCT characteristics were recorded and analyzed at presentation, after the initial 3 monthly injections and at 1 year., Results: At presentation, patients in the young group had significantly higher rates of subretinal fluid (p = 0.005), a polypoidal choroidal vasculopathy-like pattern (p < 0.01) and a history of smoking (p = 0.004). Submacular hemorrhage and pigment epithelial detachments were more common in young patients, and intraretinal fluid was more common in elderly patients (all with borderline statistical significance). VA improved significantly more in the younger patients at 3 months and 1 year (p = 0.001 and 0.002, respectively), despite similar treatment protocols and mean number of injections. Bilateral involvement at baseline was more common in elderly patients (p = 0.008). The differences in OCT characteristics between groups remained throughout the study period., Conclusion: There are considerable differences in the clinical manifestations and response to treatment between NVAMD patients at the extremities of the AMD age spectrum. Different pathophysiological, systemic, and genetic factors may play a role in such patients.

Regenerative translational studies must include a longitudinal assessment of the changes in retinal structure and function that occur as part of the natural history of the disease and those that result from the studied intervention. Traditionally, retinal structural changes have been evaluated by histological analysis which necessitates sacrificing the animals. In this review, we describe key imaging approaches such as fundus imaging, optical coherence tomography (OCT), OCT-angiography, adaptive optics (AO), and confocal scanning laser ophthalmoscopy (cSLO) that enable noninvasive, non-contact, and fast in vivo imaging of the posterior segment. These imaging technologies substantially reduce the number of animals needed and enable progression analysis and longitudinal follow-up in individual animals for accurate assessment of disease natural history, effects of interventions and acute changes. We also describe the benefits and limitations of each technology, as well as outline possible future directions that can be taken in translational retinal imaging studies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4355). The series “Novel Tools and Therapies for Ocular Regeneration” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

The main objective of this pilot study was to identify circulatory microRNAs in aqueous or plasma that were reflecting changes in vitreous of diabetic retinopathy patients. Aqueous, vitreous and plasma samples were collected from a total of 27 patients undergoing vitreoretinal surgery: 11 controls (macular pucker or macular hole patients) and 16 with diabetes mellitus(DM): DM-Type I with proliferative diabetic retinopathy(PDR) (DMI-PDR), DM Type II with PDR(DMII-PDR) and DM Type II with nonproliferative DR(DMII-NPDR). MicroRNAs were isolated using Qiagen microRNeasy kit, quantified on BioAnalyzer, and profiled on Affymetrix GeneChip miRNA 3.0 microarrays. Data were analyzed using Expression Console, Transcriptome Analysis Console, and Ingenuity Pathway Analysis. The comparison analysis of circulatory microRNAs showed that out of a total of 847 human microRNA probes on the microarrays, common microRNAs present both in aqueous and vitreous were identified, and a large number of unique microRNA, dependent on the DM type and severity of retinopathy. Most of the dysregulated microRNAs in aqueous and vitreous of DM patients were upregulated, while in plasma, they were downregulated. Dysregulation of miRNAs in aqueous did not appear to be a good representative of the miRNA abundance in vitreous, or plasma, although a few potential candidates for common biomarkers stood out: let-7b, miR-320b, miR-762 and miR-4488. Additionally, each of the DR subtypes showed miRNAs that were uniquely dysregulated in each fluid (i.e. aqueous: for DMII-NPDR was miR-455-3p; for DMII-PDR was miR-296, and for DMI-PDR it was miR-3202). Pathway analysis identified TGF-beta and VEGF pathways affected. The comparative profiling of circulatory miRNAs showed that a small number of them displayed differential presence in diabetic retinopathy vs. controls. A pattern is emerging of unique molecular microRNA signatures in bodily fluids of DR subtypes, offering promise for the use of ocular fluids and plasma for diagnostic and therapeutic purposes., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate the accuracy and uniformity of the definitions used to diagnose vitreoretinal (VR) interface disorders and to assess it after review of its definitions., Methods: A case-series study, consisting of a questionnaire of 46 optical coherence tomography images of six VR interface disorders: vitreomacular adhesion, vitreomacular traction, epiretinal membrane, full-thickness macular hole, lamellar macular hole, and pseudohole. Images were presented to 41 practicing ophthalmologists (13 residents, 11 VR specialists, and 17 non-VR specialists), and a diagnosis was recorded for each image. The questionnaire was repeated after review of the International Vitreomacular Traction Study (IVTS) group classification. Rates of accuracy and uniformity for each condition were analyzed., Results: Overall correct identification rates according to the IVTS classification were achieved in 67.4% of cases and were highest for epiretinal membrane and full-thickness macular hole, followed by vitreomacular adhesion, vitreomacular traction, and lamellar macular hole, and were significantly lower for pseudohole (P < 0.001). Accuracy was higher among VR specialists and was associated with previous familiarity with the IVTS classification (P = 0.043) but not with length of experience in ophthalmology (P = 0.74). After review of the IVTS classification, overall correct identification rates improved to 71.7% (P = 0.004), with the significant improvement in pseudohole identification (P = 0.002)., Conclusion: The IVTS classification is effective in standardizing the diagnosis of VR interface disorders. It is expected to become increasingly assimilated among ophthalmologists over time, leading to higher rates of accuracy and uniformity in diagnosing VR interface disorders.

Purpose: To evaluate the visual and anatomical outcomes of reoperations following failure of pneumatic retinopexy (PR) for rhegmatogenous retinal detachment repair and compare the different surgical techniques used in these cases., Methods: The study included 114 eyes of 114 patients who underwent PR for rhegmatogenous retinal detachment and required subsequent surgery for its repair. These included repeated PR, scleral buckling, vitrectomy with gas or silicone oil, and vitrectomy with scleral buckling. The groups were compared for rates of retinal reattachment, visual improvement, and the occurrence of recurrent rhegmatogenous retinal detachment and any other postoperative complications., Results: In 91 (79.8%) eyes, the retina was reattached with one additional procedure. The success rate was significantly lower in eyes treated by repeated PR than by other surgical techniques (33 vs. 76-90%; P < 0.001). Visual acuity after PR failure was not significantly different than that at presentation and had improved significantly after surgery for retinal reattachment (P < 0.001)., Conclusion: Pneumatic retinopexy failure was not associated with visual acuity loss, and the outcomes in 79.2% of cases that required only one additional surgery are comparable with those achieved with primary surgery. Poor outcomes were associated with eyes that required more than one additional surgery and that suffered complications.

Purpose: To analyze the 100 most-cited articles on pars plana vitrectomy (PPV)., Design: Bibliographic study., Methods: Literature search using the bibliographic databases of the ISI Web of Knowledge, limited to research articles published between 1971 and 2018 in peer-reviewed journals of ophthalmology., Main Outcome Measure: Number of citations since publication., Results: The 100 most-cited articles on PPV were published in 11 different ophthalmology journals, with 73 of them published in Ophthalmology (n = 31), American Journal of Ophthalmology (n = 26), and Archives of Ophthalmology (n = 16). They originated from 14 different countries, predominantly from the United States (n = 64), and 99 of them were written in English. Their topics cover a wide spectrum of retinal conditions that vary from decade to decade as the technique of PPV evolved and became applicable to more indications., Conclusions: This bibliographic study provides a unique historic perspective of the development of PPV and its applications from its introduction to its current status., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the outcomes of laser retinopexy for the treatment of retinal tears between residents and specialists, and to identify tear characteristics associated with the risk of progression to retinal detachment (RD)., Methods: A retrospective review of 307 eyes treated by laser retinopexy, categorized by the performing physician, either a resident (217 cases) or a specialist (90 cases). Recorded parameters included the number, size, and location of the retinal tears, the presence of bridging vessels, vitreous hemorrhage (VH), or subretinal fluid (SRF), the need for additional laser, progression to RD, and surgery., Results: Additional laser was performed in 42.3% of cases in the resident group and 35.5% in the specialist group (p = 0.26). Progression to RD occurred in 6.9% of cases in the resident group and 5.5% in the specialist group (p = 0.66). The presence of VH and SRF were associated with an increased risk of progression to RD (p < 0.0001 and 0.003, respectively). A higher proportion of cases with SRF were treated by specialists (p = 0.006)., Conclusions: Laser retinopexy is safely and effectively performed by residents, with no worse outcomes than procedures performed by specialists. A high rate of additional laser may be needed to achieve RD prophylaxis, and higher-risk cases can be identified at presentation and then referred to specialists., (© 2020 S. Karger AG, Basel.)

Purpose: To evaluate the accuracy and precision of anti-vascular endothelial growth factor volume delivery by intravitreal injections in the clinical setup., Methods: Volume output was measured in 669 intravitreal injections administered to patients, calculated from the difference in syringe weight before and after expelling the drug. Three groups were included: prefilled bevacizumab 1.0 mL syringe (Group 1, n = 432), pre-filled ranibizumab in a small-volume syringe with low dead-space plunger design (Group 2, n = 125), and aflibercept drawn and injected using a 1.0-mL syringe (Group 3, n = 112). Accuracy was analyzed by mean absolute percentage error, and precision by coefficient of variation., Results: Volume outputs in all 3 groups were significantly different from the target of 50 μL (P < 0.0001 for all), and mean absolute percentage error values were 12.25% ± 5.92% in Group 1, 13.60% ± 8.75% in Group 2, and 24.69% ± 14.84% in Group 3. No difference was found between groups 1 and 2, but both were significantly more accurate than Group 3 (P < 0.0001 for both)., Conclusion: The current practices used for intravitreal injections are highly variable, with overdelivery of the anti-vascular endothelial growth factor drugs measured in most cases, but underdelivery in 16.3% of injections. Use of a prefilled syringe was associated with improved accuracy, and low dead-space plunger design may improve precision.