PURPOSE:To evaluate whether posterior segment imaging findings in ocular syphilis demonstrate reproducible temporal patterns relative to symptom duration. DESIGN:Retrospective case series. METHODS:Patients diagnosed with ocular syphilis between 2015 and 2025 were retrospectively reviewed. Posterior segment imaging was graded across color fundus photography, fluorescein angiography, optical coherence tomography, and near-infrared reflectance. Imaging findings observed in ≥5 eyes were evaluated across symptom-duration intervals and compared between earlier and later presentations using generalized estimating equation (GEE) logistic regression to account for within-patient correlation. Hierarchical clustering and principal component analysis (PCA) were used to characterize temporal imaging patterns. Associations between symptom duration and laboratory parameters, including rapid plasma reagin (RPR) titers and cerebrospinal fluid (CSF) markers, were assessed using Spearman correlation. RESULTS:Forty patients (73 eyes) were included, with posterior segment imaging available in 24 patients (46 eyes). Imaging abnormalities were more frequently detected among patients presenting earlier after symptom onset (≤8 weeks). OCT disc edema was significantly enriched in earlier presentations, while paravenous retinal edema, outer retinal white spots, and near-infrared linear reflectivity change demonstrated similar temporal trends. Several structural abnormalities, including placoid lesions, ellipsoid zone disruption, and subretinal hyperreflective lesions, were observed across all symptom-duration intervals. Hierarchical clustering identified 4 distinct temporal patterns of imaging findings, with PCA providing complementary visualization of feature relationships. RPR titers showed a moderate inverse correlation with symptom duration (r = -0.45, P = .004), while CSF parameters demonstrated similar but nonsignificant negative trends. CONCLUSIONS:Posterior segment imaging findings in ocular syphilis demonstrate nonrandom temporal patterns that may inform clinical interpretation relative to symptom duration.

PURPOSE:To examine the progression of hydroxychloroquine retinopathy (HCR) from the time of drug cessation to the last follow-up. DESIGN:Retrospective, consecutive case series SUBJECTS: 17 patients with HCR in whom drug was stopped and follow-up maintained. METHODS:Charts, visual fields, and retinal images were reviewed. Four ancillary studies were investigated: 10-2 visual fields (10-2 VF), multifocal electroretinography (mfERG), spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) imaging. Retinopathy was graded as none, early, and advanced. MAIN OUTCOME MEASURES:Progression of retinopathy by the four test methods. RESULTS:Of the 17 patients, the numbers with at least two follow-up studies to allow comparison for progression were 17, 8, 16, and 9 for 10-2 VF, mfERG, SD-OCT, and FAF, respectively. Median follow-ups were 25, 22, 41, and 37 months for 10-2 VF, mfERG, SD-OCT, and FAF, respectively. The proportions of eyes with no retinopathy at drug cessation that progressed were 0/0, 3/5, 0/0, and 2/6 for 10-2 VF, mfERG, SD-OCT, and FAF, respectively. The proportions of eyes with early retinopathy that progressed were 4/6, 0/6, 2/15, and 3/7 for 10-2 VF, mfERG, SD-OCT, and FAF, respectively. The proportions of eyes with advanced retinopathy that progressed were 16/20, 0/5, 10/17, and 5/5 for 10-2 VF, mfERG, SD-OCT, and FAF, respectively. Progression of retinopathy was seen in cases without retinal pigment epithelium loss at the time of drug cessation. Not all ancillary studies show retinopathy at the time of diagnosis of HCR. Multifocal ERG shows a floor effect. Once response densities are low, detecting further progression of toxicity by this modality is not possible. A greater breadth of retinopathy progression is possible with 10-2 VF, SD-OCT, and FAF. CONCLUSIONS:If HC is stopped when decreased reflectivity of the parafoveal ellipsoid zone is detected by SD-OCT, the probability of retinopathy progression is low. The cut point at which progression of retinopathy is acknowledged to be likely despite drug cessation needs to be moved earlier to discontinuity of the ellipsoid zone.

OBJECTIVE:To develop and evaluate Atrophy Advisor, a clinical decision tool integrating geographic atrophy (GA) progression and personalized lifespan estimates to help clinicians considering complement factor inhibitor injections for dry macular degeneration with GA. DESIGN:Retrospective cohort study. SUBJECTS:Fifty consecutive patients with GA secondary to nonexudative age-related macular degeneration, seen at Wake Forest-affiliated retina clinics from May 2013 to June 2025. METHODS:Fundus images at two or more time points were analyzed using ImageJ to measure the distance from the fovea to the nearest GA edge. Pixel-to-micron conversion was made using an assumed vertical disk diameter of 1800 microns. Demographics, comorbidities, and corrected visual acuities were extracted from records. Lifespan estimates were calculated using University of Connecticut and Social Security Administration algorithms and compared to observed outcomes. MAIN OUTCOME MEASURES:GA edge-to-fovea distance, GA progression rate, corrected visual acuity, and predicted vs observed lifespan. RESULTS:Median age was 78 years (IQR: 74-82); 64% were female. Baseline median GA-to-fovea distance was 792 µm (IQR: 508-1213 µm), declining to 395 µm (IQR: 194-702 µm) at last follow-up. Median GA progression was 122 µm/y (range 2-626 µm/y), with a direct relationship between initial distance and progression rate (P = .006, R² = 0.146). Lifespan calculators (University of Connecticut and Atrophy Advisor) yielded median estimates of 11.9 and 11.0 years, respectively, influencing treatment guidance in 4% of cases. CONCLUSIONS:Atrophy Advisor is feasible for combining GA progression kinetics and lifespan estimates to inform treatment decisions. Variability in progression rates and lifespan predictions highlights the need for personalized approaches. Limitations include measurement variability and retrospective design; future studies should validate the tool in larger, prospective cohorts.

center dot PURPOSE: To discuss the history and current state of private equity in ophthalmology, and to explore potential implications for ophthalmology practices, physicians, and patients. center dot DESIGN: Perspective. center dot METHODS: Selected articles in ophthalmology and non- ophthalmology medical literature were reviewed, and commentary is provided based on the authors' experiences. center dot RESULTS: Investment in ophthalmology appeals to private equity firms because of high procedural volumes, fragmented private practices, opportunities for real estate ownership, and an aging population in need of eye care. As a result, acquisition of private practices by large private equity companies has swelled since 2015. Metropolitan areas and practices that possess ambulatory surgical centers or a high proportion of retina surgeons receive the greatest investment. However, little objective data exist regarding the benefits of this trend. Initial research suggests that private equity ownership may have a negative impact on patient care through greater costs, shorter appointments, and fewer Medicare/Medicaid patients seen. Skeptics of private equity also highlight concerns that include financial risk falling primarily on the acquired practice itself, a short-term business approach that rewards profit maximization, and the erosion of physician autonomy. Furthermore, young ophthalmologists express reservations about working for private equity firms. In all, 78% of trainees indicated that they would not consider employment by a private equity-owned practice, and 81.4% of vitreoretinal fellows voiced concerns about autonomy and job security. Proposed legislation aimed at limiting private equity acquisitions is currently under review at the statewide level, adding additional uncertainty to the future of private equity involvement in ophthalmology. center dot CONCLUSIONS: Although investment by private equity offers potential financial rewards and operational improvements for practices, it also raises significant concerns reminiscent of those experienced by physician practice management companies in the 1990s . Non-anecdotal data are needed to assess the benefits and future of private equity involvement in ophthalmology. (Am J Ophthalmol 2025;270: 245-251. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction:The purpose of this study was to evaluate the progression of hydroxychloroquine (HCQ) retinopathy following parafoveal loss of the ellipsoid zone (EZ) without retinal pigment epithelium damage (RPE). Methods:This was a single-center retrospective case series of patients with hydroxychloroquine retinopathy who presented between 2012 and 2023 and in whom the drug was stopped prior to damage of the RPE. Patient imaging from the time of HCQ discontinuation to the most recent follow up appointment was reviewed to assess for retinopathy progression, and spectral domain optical coherence tomography (SD-OCT) images were analyzed using ImageJ2 to quantify ellipsoid zone damage. Results:Five patients met the criteria for inclusion in this study. All patients were female, with a mean age of 69.5 ± 12.2 years. Patients had been taking HCQ for 18.2 years on average (range: 5-32 years). 40% of patients were overdosed according to real weight guidelines and 60% by ideal weight guidelines. All patients demonstrated worsening of retinopathy following drug discontinuation. The length of parafoveal zones of EZ hyporeflectivity on SD-OCT increased by an average of 26.8 ± 8.6% in right eyes and 22.5 ± 15.0% in left eyes over an average follow-up period of 31.4 months (range 8-71 months). Conclusion:Progression of HCQ retinopathy can occur even when HCQ is discontinued before RPE damage. Ophthalmologists should be aware of the risks associated with HCQ use following damage to the EZ. The acknowledged threshold at which irreversible progression of retinopathy is predicted despite cessation of the drug may need to be reconsidered and shifted earlier than RPE loss.

Purpose: To report updated clinical outcomes in subjects undergoing pars plana vitrectomy (PPV) using modern techniques and equipment for the treatment of proliferative diabetic retinopathy-related complications. Pooled analysis of five randomized clinical trials conducted at the same institution and included both study and control subjects from the trials. Methods: There were 943 subjects who prospectively underwent small-gauge PPV with antivascular endothelial growth factor pretreatment for proliferative diabetic retinopathy-related complications and completed 6-month follow-up. Results: The visual acuity of the study population improved from median 2.00 (interquartile range 1.3, 2.3) at baseline to median 1.00 (interquartile range 0.5, 1.3) at 6 months. One hundred and eighty-four patients (19.5%) achieved 20/50 or better acuity, and 652 patients (69.1%) achieved 20/200 or better acuity at 6 months. The vision improved or remained stable in 901 patients (95.5%), and 11 patients (1.2%) developed no light perception at 6 months. Intraoperative complications occurred in 343 cases (36.4%), and 199 cases (21.1%) experienced a postoperative complication. The most common postoperative complication was vitreous hemorrhage in 124 cases (62.3% of all complications). Unplanned secondary PPV was necessary in 86 cases (9.1%). Conclusion: This study reports updated clinical outcomes in patients undergoing PPV for proliferative diabetic retinopathy-related complications which compares favorably with the age before small-gauge PPV and antivascular endothelial growth factor pretreatment.

Intravitreal anti-vascular endothelial growth factor (VEGF) injections are commonly used to treat eyes with macular edema secondary to hemiretinal vein occlusion (HRVO) or central retinal vein occlusion (CRVO). Information on whether differences exist in outcomes after anti-VEGF therapy can help guide treatment for each of the different disease types.To compare baseline characteristics, treatment burden, and outcomes of macular edema treatment in participants with HRVO with those of participants with CRVO.This post hoc outcome analysis from the Study of Comparative Treatments for Retinal Vein Occlusion 2 randomized clinical trial included 362 participants with macular edema caused by HRVO or CRVO treated at 66 US sites. Randomization began in September 2014, and the last month 24 follow-up visit occurred in February 2018. Data were analyzed from April 2020 to May 2021.Eyes were initially randomized to 6 monthly intravitreal injections of aflibercept or bevacizumab and were treated according to protocol between months 6 to 12 depending on 6-month outcome. After month 12, patients were treated per investigator discretion and observed through month 60.Mean visual acuity letter score (VALS).Of 362 included patients, 157 (43.4%) were female, and the mean (SD) age was 68.9 (12.0) years. Outcome data were analyzed up to month 24 owing to substantial missing data at later visits. A significantly greater proportion of participants with HRVO than those with CRVO were Black (37% vs 11%). Treatment rates between months 12 to 23 were 0.36 (95% CI, 0.32-0.40) injections per month for patients with CRVO and 0.28 (95% CI, 0.19-0.36) for patients with HRVO (P = .11). The mean VALS from months 1 to 24 of an HRVO study eye exceeded that of a CRVO study eye by 5.5 (95% CI, 1.5-9.5; P = .01), consistent with the magnitude of the VALS difference between eyes with CRVO and HRVO at baseline. Eyes with CRVO presented at baseline with more macular edema than eyes with HRVO (difference in central subfield thickness [CST], 86 μm; 95% CI, 48-124; P < .001), with no difference in CST between the groups throughout months 1 to 24.Black race was more prevalent among participants with HRVO than CRVO, and no differences were observed in the frequency of treatments for macular edema between eyes with CRVO and HRVO. Although eyes with CRVO presented with worse visual acuity and more macular edema on average than did eyes with HRVO, the magnitude of VALS improvement, central retinal thickness in response to anti-VEGF therapy, and treatment burden were similar between the groups.

Purpose: To report updated clinical outcomes in subjects undergoing pars plana vitrectomy (PPV) using modern techniques and equipment for the treatment of proliferative diabetic retinopathy–related complications. Pooled analysis of five randomized clinical trials conducted at the same institution and included both study and control subjects from the trials. Methods: There were 943 subjects who prospectively underwent small-gauge PPV with antivascular endothelial growth factor pretreatment for proliferative diabetic retinopathy–related complications and completed 6-month follow-up. Results: The visual acuity of the study population improved from median 2.00 (interquartile range 1.3, 2.3) at baseline to median 1.00 (interquartile range 0.5, 1.3) at 6 months. One hundred and eighty-four patients (19.5%) achieved 20/50 or better acuity, and 652 patients (69.1%) achieved 20/200 or better acuity at 6 months. The vision improved or remained stable in 901 patients (95.5%), and 11 patients (1.2%) developed no light perception at 6 months. Intraoperative complications occurred in 343 cases (36.4%), and 199 cases (21.1%) experienced a postoperative complication. The most common postoperative complication was vitreous hemorrhage in 124 cases (62.3% of all complications). Unplanned secondary PPV was necessary in 86 cases (9.1%). Conclusion: This study reports updated clinical outcomes in patients undergoing PPV for proliferative diabetic retinopathy–related complications which compares favorably with the age before small-gauge PPV and antivascular endothelial growth factor pretreatment.

To describe the characteristics of Japanese patients with hydroxychloroquine (HCQ) retinopathy developing within 3 years of treatment outset. Retrospective case series Three patients with HCQ retinopathy developing within 3 years of treatment outset have been identified in Japan since HCQ became available in 2015. Their medical charts, containing optical coherence tomography (OCT), fundus autofluorescence imaging, and visual field tests, were reviewed. The treatment durations and cumulative doses until onset were 29–36 months and 182–326 g, respectively. The first patient had possible pre-existing maculopathy, although the abnormalities were ambiguous. The second and third patients had impaired renal function. The patients did not complain of severe visual disturbance at diagnosis, but visual field loss and disruption of the outer retinal segments consisting of a parafoveal pattern in the first case and a pericentral pattern (localized, 8 or more degrees from the center of the fovea) in the second and third cases were clearly observed on OCT. Even after HCQ discontinuation, their retinopathy showed slight progression on the visual field tests and OCT images. A blood sample was obtained from 1 patient on the day after HCQ discontinuation, and the whole blood level of HCQ was measured using validated liquid chromatography-tandem mass spectrometry. The HCQ level 27 h after the last dose was high, at 2240 ng/mL (suggested threshold > 1733 ng/mL). Ophthalmologic screening from the initiation of HCQ treatment detected 3 cases of HCQ retinopathy developing within 3 years of treatment outset, including a patient with a high blood level of HCQ.

Purpose: To quantify the economic incentives associated with the choice of anti-VEGF drugs for retinal diseases. Methods: An economic model was created based on the distribution of use and number of injections of bevacizumab (B), versus aflibercept or ranibizumab (AR); published Medicare reimbursement rates; published rebates; estimated unreimbursed drug use; estimated use of drug company samples; and published costs-of-drugs. Differential economic incentives associated with the choice of drugs were calculated over a range of distributions of drug use. Results: The splits in drug choice ranged from 92% AR/8% B to 31% AR/69% B, and in annual injection numbers from 2000 to 6000 with a median of 4000 in one 5-person retina service. Assumed values for rebates were 1% for drug company rebate, 1% for group purchasing organization rebate, and 5 for number of unreimbursed injections per year. The differential economic incentive of a 92% AR/8% B split compared to a 31% AR/69% B split for the median annual number of injections was $266, 893. Conclusion: Using real-world data, the economic incentive associated with a choice of more expensive anti-VEGF drugs is large. Accounting for unreimbursed drug use and the cost of additional staff required to manage expensive drug inventory does not nullify the incentive. To what degree this financial incentive influences ophthalmologists' choice of drugs is unknown, but not trivial. Financial disclosure of the conflicts of interest in the drugs recommended for treatment should be discussed with patients.

Arthritis & RheumatologyVolume 73, Issue 2 p. 358-359 Letter Early-Onset Hydroxychloroquine Retinopathy and a Possible Relationship to Blood Levels: Comment on the Article by Petri et al Naoto Yokogawa, Corresponding Author Naoto Yokogawa [email protected] orcid.org/0000-0002-7814-443X Tokyo Metropolitan Tama Medical CenterSearch for more papers by this authorAkiko Ohno-Tanaka, Akiko Ohno-Tanaka Tokyo Metropolitan Tama Medical CenterSearch for more papers by this authorMasayuki Hashiguchi, Masayuki Hashiguchi Keio University, Tokyo, JapanSearch for more papers by this authorMikiko Shimizu, Mikiko Shimizu Shujitsu University School of Pharmacy, Okayama, JapanSearch for more papers by this authorHiroko Ozawa, Hiroko Ozawa Kawasaki Municipal Hospital, Kanagawa, JapanSearch for more papers by this authorShinji Ueno, Shinji Ueno Nagoya University, Nagoya, JapanSearch for more papers by this authorKei Shinoda, Kei Shinoda Saitama Medical University, Saitama, JapanSearch for more papers by this authorDavid J. Browning, David J. Browning Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, NCSearch for more papers by this author Naoto Yokogawa, Corresponding Author Naoto Yokogawa [email protected] orcid.org/0000-0002-7814-443X Tokyo Metropolitan Tama Medical CenterSearch for more papers by this authorAkiko Ohno-Tanaka, Akiko Ohno-Tanaka Tokyo Metropolitan Tama Medical CenterSearch for more papers by this authorMasayuki Hashiguchi, Masayuki Hashiguchi Keio University, Tokyo, JapanSearch for more papers by this authorMikiko Shimizu, Mikiko Shimizu Shujitsu University School of Pharmacy, Okayama, JapanSearch for more papers by this authorHiroko Ozawa, Hiroko Ozawa Kawasaki Municipal Hospital, Kanagawa, JapanSearch for more papers by this authorShinji Ueno, Shinji Ueno Nagoya University, Nagoya, JapanSearch for more papers by this authorKei Shinoda, Kei Shinoda Saitama Medical University, Saitama, JapanSearch for more papers by this authorDavid J. Browning, David J. Browning Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, NCSearch for more papers by this author First published: 28 August 2020 https://doi.org/10.1002/art.41497Citations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume73, Issue2February 2021Pages 358-359 RelatedInformation

PURPOSE: To describe the rationale for revising the hydroxychloroquine (HCQ) dosing and screening guidelines and to identify the barriers to more effective guidelines in the future. DESIGN: Literature review. METHODS: A PubMed query of studies on HCQ dosing and HCQ retinopathy (HCQR) screening was conducted with a selective review of the English language literature. RESULTS: Three iterations of the American Academy of Ophthalmology HCQ dosing and HCQR screening guidelines have been published without including prescribing physicians on the writing committees. This may contribute to prescribing physicians' low adherence to the guidelines. As ancillary tests have improved, asymptomatic HCQR is being detected earlier, leading to a higher reported prevalence of HCQR and a drop in the ceiling for safe dosing. These trends put stricter constraints on prescribers and their patients, who may have had well-controlled autoimmune disease on HCQ doses that were previously considered to be below the highrisk threshold for HCQR. Indeed, stopping HCQ at the earliest sign of HCQR should be reconsidered; for cases of early HCQR, dose reduction and more intensive monitoring for retinopathy may strike a more appropriate balance between HCQ risk and benefits. A prospective study using the Diabetic Retinopathy Clinical Research Retina Network with standardized collection of data, HCQblood levels, centralized grading of ancillary tests, and community and academic ophthalmologists would provide a stronger evidence base for future HCQ guidelines. CONCLUSIONS: The HCQ dosing and screening guidelines should be updated and a prospective study of HCQ dosing andHCQR should be initiated with the joint efforts of ophthalmologists and prescribing physicians. (C) 2020 Elsevier Inc. All rights reserved.

The first reports of severe uveitis and occlusive retinal vasculitis associated with the use of brolucizumab (Beovu; Novartis, East Hanover, New Jersey, USA) appeared in early February of 2020, and more have appeared since then. Novartis sent information on the postapproval development to users on February 25 and updates have followed.1Novartis provides update on use and safety of Beovu® in patients with wet AMD.https://www.novartis.com/news/novartis-provides-update-use-and-safety-beovu-patients-wet-amdDate accessed: May 3, 2020Google Scholar Twenty-six cases associated with 70,000 injections and 37,000 treated patients were reported by March 27, 2020, in a report by the American Society of Retina Specialists (ASRS) Research and Safety in Therapeutics (ReST) Committee.2American Society of Retina Specialists Research and Safety in Therapeutics Committee.https://www.asrs.org/about/committees/51Date: 2020Date accessed: May 3, 2020Google Scholar Although the ASRS ReST committee report was not publicly available, the American Academy of Ophthalmology (AAO) has provided an available audio report on these recent developments surrounding brolucizumab-induced inflammation.3American Academy of Ophthalmology Audio Episode 227: the ASRS ReST Report on Brolucizumab.https://www.aao.org/audio/episode-227-asrs-rest-report-on-brolucizumab-withDate: 2020Date accessed: May 3, 2020Google Scholar Neither the Novartis warning nor the latest ASRS ReST committee's report from April 7 recommended that brolucizumab injections be stopped, but they did recommend careful evaluation for inflammation and continued vigilance in monitoring brolucizumab treatment outcomes. However, for many of us, these recommendations did not go far enough, and we have stopped using brolucizumab because of the associated inflammation. Our patients have alternatives without incurring this risk. When brolucizumab became commercially available in late 2019, the retinal community was enthusiastic about this newest vascular endothelial growth factor (VEGF) inhibitor for the treatment of exudative age-related macular degeneration (eAMD). Brolucizumab offered the hope of fewer intravitreal injections for patients with eAMD.4Nguyen Q.D. Das A. Do D.V. et al.Brolucizumab: evolution through preclinical and clinical studies and the implications for the management of neovascular age-related macular degeneration.Ophthalmology. 2020; https://doi.org/10.1016/j.ophtha.2019.12.031Abstract Full Text Full Text PDF Scopus (135) Google Scholar The brolucizumab phase 3 studies suggested greater durability with similar visual acuity outcomes compared with aflibercept (Eylea; Regeneron, Tarrytown, New York, USA). Who wouldn't want fewer injections into their eye and comparable visual acuity results? With good reason, both patients and clinicians embraced this new drug. However, soon after the widespread community adoption of brolucizumab, sporadic reports began to surface that patients were experiencing severe sterile inflammation that could be difficult to distinguish from infectious endophthalmitis. Although cases of severe sterile noninfectious intraocular inflammation have been reported following the injection of other anti-VEGF drugs,5Ladas I.D. Karagiannis D.A. Rouvas A.A. Kotsolis A.I. Liotsou A. Vergados I. Safety of repeat intravitreal injections of bevacizumab versus ranibizumab: our experience after 2,000 injections.Retina. 2009; 29: 313-318Crossref PubMed Scopus (106) Google Scholar, 6Martin D.F. Maguire M.G. Ying G.S. et al.CATT Research GroupRanibizumab and bevacizumab for neovascular age-related macular degeneration.N Engl J Med. 2011; 364: 1897-1908Crossref PubMed Scopus (2298) Google Scholar, 7Martin D.F. Maguire M.G. Fine S.L. et al.Comparison of Age-related Macular Degeneration Treatments Trials Research GroupRanibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results.Ophthalmology. 2012; 119: 1388-1398Abstract Full Text Full Text PDF PubMed Scopus (1522) Google Scholar, 8Goldberg R.A. Shah C.P. Wiegand T.W. Heier J.S. Noninfectious inflammation after intravitreal injection of aflibercept: clinical characteristics and visual outcomes.Am J Ophthalmol. 2014; 158: 733-737.e1Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar, 9Khanani A.M. Cohen G.L. Zawadzki R. A prospective masked clinical assessment of inflammation after intravitreal injection of ranibizumab or aflibercept.J Ocul Pharmacol Ther. 2016; 32: 216-218Crossref PubMed Scopus (25) Google Scholar, 10Kitchens J.W. Do D.V. Boyer D.S. et al.Comprehensive review of ocular and systemic safety events with intravitreal aflibercept injection in randomized controlled trials.Ophthalmology. 2016; 123: 1511-1520Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 11Souied E.H. Dugel P.U. Ferreira A. Hashmonay R. Lu J. Kelly S.P. Severe ocular inflammation following ranibizumab or aflibercept injections for age-related macular degeneration: a retrospective claims database analysis.Ophthalmic Epidemiol. 2016; 23: 71-79Crossref PubMed Scopus (47) Google Scholar this brolucizumab-associated inflammation was unusual because it was associated with an occlusive vasculitis and irreversible severe vision loss, albeit rare.12Baumal C.R. Spaide R.F. Vajzovic L. et al.Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab.Ophthalmology. 2020; https://doi.org/10.1016/j.ophtha.2020.04.017Abstract Full Text Full Text PDF Scopus (197) Google Scholar, 13Haug S.J. Hien D.L. Uludag G. et al.Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration.Am J Ophthalmol Case Rep. 2020; 18: 100680Crossref PubMed Scopus (103) Google Scholar, 14Jain A. Chea S. Matsumiya W. et al.Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations.Am J Ophthalmol Case Rep. 2020; 18: 100687Crossref PubMed Scopus (84) Google Scholar This unpredictable severe inflammation could develop weeks after the last brolucizumab injection even if previous injections of brolucizumab were well tolerated, so previous brolucizumab injections without inflammation were no guarantee that subsequent injections would be safe.12Baumal C.R. Spaide R.F. Vajzovic L. et al.Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab.Ophthalmology. 2020; https://doi.org/10.1016/j.ophtha.2020.04.017Abstract Full Text Full Text PDF Scopus (197) Google Scholar, 13Haug S.J. Hien D.L. Uludag G. et al.Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration.Am J Ophthalmol Case Rep. 2020; 18: 100680Crossref PubMed Scopus (103) Google Scholar, 14Jain A. Chea S. Matsumiya W. et al.Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations.Am J Ophthalmol Case Rep. 2020; 18: 100687Crossref PubMed Scopus (84) Google Scholar The retinal community had not reported this type of vision-threatening occlusive retinal vasculitis after intravitreal injections of other commonly used anti-VEGF drugs, such as aflibercept, bevacizumab (Avastin; Genentech, South San Francisco, California, USA), and ranibizumab (Lucentis; Genentech). Retinal specialists started sharing this brolucizumab information with each other through social media, at meetings, and through published reports.12Baumal C.R. Spaide R.F. Vajzovic L. et al.Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab.Ophthalmology. 2020; https://doi.org/10.1016/j.ophtha.2020.04.017Abstract Full Text Full Text PDF Scopus (197) Google Scholar, 13Haug S.J. Hien D.L. Uludag G. et al.Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration.Am J Ophthalmol Case Rep. 2020; 18: 100680Crossref PubMed Scopus (103) Google Scholar, 14Jain A. Chea S. Matsumiya W. et al.Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations.Am J Ophthalmol Case Rep. 2020; 18: 100687Crossref PubMed Scopus (84) Google Scholar Unlike our previous experience with inflammatory outbreaks when using other anti-VEGF drugs, there had been no previous history of safe routine clinical use of brolucizumab before these reports of inflammation surfaced, so one of our initial impressions of this drug was one of heightened concern. Retina specialists deserve credit for identifying this problem early and notifying the appropriate authorities. They alerted Novartis, their specialty societies, and the Food and Drug Administration (FDA). As a result, both the ASRS and Novartis established committees to investigate this brolucizumab-induced inflammation. Novartis has willingly refunded the cost of any previously purchased brolucizumab to retina practices. However, brolucizumab remains on the market and continues to be used with the cautious approval of both the ASRS and Novartis. Amid mounting speculation as to the underlying cause of this brolucizumab-associated inflammation, we all want the investigations to continue so we can learn the truth behind these adverse events. Whatever is learned from these ongoing investigations will provide invaluable information for anyone developing an agent for injection into the eye. But as this process plays out, it is our view that intravitreal injections of brolucizumab should stop. Brolucizumab is not the only drug that can be used for the treatment of eAMD. In the face of the known risk, its use is unwarranted. We praise the postmarketing surveillance of the vitreoretinal community in identifying these never-events, but now we need the ASRS, the Retina Society, the Macular Society, the AAO, and the FDA to make official what many retina specialists have already implemented—a moratorium on its use until the results of further investigations are concluded and remedies are implemented. Brolucizumab could fly again, but not until these safety concerns are addressed. Funding/Support: No funding or grant support. Financial Disclosures: Philip Rosenfeld receives research support from Carl Zeiss Meditec, Inc, and Stealth BioTherapeutics. He is also a consultant for Apellis, Biogen, Boehringer-Ingelheim, Carl Zeiss Meditec, Chengdu Kanghong Biotech, EyePoint, Ocunexus Therapeutics, Ocudyne, and Unity Biotechnology. Philip Rosenfeld has equity interest in Apellis, Valitor, Verana Health, and Ocudyne. David Browning receives research support from the DRCR Retina.net and Regeneron. He has an equity interest in Zeiss-Meditec. He receives royalties from Springer Inc. Prashanth Iyer, MD provided valuable background research support for this Editorial. All authors attest that they meet the current ICMJE criteria for authorship. Comment on: Is this a 737 Max Moment for BrolucizumabAmerican Journal of OphthalmologyVol. 223PreviewWe read with interest the editorial titled "Is this a 737 Max Moment for Brolucizumab."1 At Novartis, providing safe and effective treatments for patients is our highest priority. Working closely with health authorities around the world, including FDA, we continuously monitor the benefit-risk profile of our medicines. Although other anti–vascular endothelial growth factor (anti-VEGF) agents are available, there are current unmet needs with neovascular AMD (nAMD) treatment that we believe brolucizumab addresses. Full-Text PDF

The structure and functions of the choroid have been long acknowledged but the pathophysiology behind various anomalies has been difficult to understand until the advent of optical coherence tomography (OCT).With OCT imaging, choroidal cavitations appear as optically empty spaces between the outer retinal and choroidal layers with attenuation or loss of outer retinal layers.Choroidal cavitations are found in the posterior pole and seen in conditions such as pathologic myopia, north carolina macular dystrophy (NCMD), focal choroidal excavation (FCE), and torpedo maculopathy (TM).To date, these disorders have not been linked.A commonality they all share is malformation of the RPE-photoreceptorchoroid complex.The following report describes the differences and similarities of choroidal cavitation amongst the different retinal disorders and emphasizes the importance of multimodal imaging in the detection and management of potential complications.

We read the Correspondence by Kayath and Sauer 1 Kayath M. Sauer D. Comment on: "Is this a 737 Max Moment for Brolucizumab?". Am J Ophthalmol. 2020; https://doi.org/10.1016/j.ajo.2020.06.035 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar from Novartis Pharmaceuticals with interest. Their letter fails to disclose the recent clarifications in the HAWK and HARRIER trial data, and by doing so they fail to reveal the true risks and benefits for the patients who might be given brolucizumab. Comment on: Is this a 737 Max Moment for BrolucizumabAmerican Journal of OphthalmologyVol. 223PreviewWe read with interest the editorial titled "Is this a 737 Max Moment for Brolucizumab."1 At Novartis, providing safe and effective treatments for patients is our highest priority. Working closely with health authorities around the world, including FDA, we continuously monitor the benefit-risk profile of our medicines. Although other anti–vascular endothelial growth factor (anti-VEGF) agents are available, there are current unmet needs with neovascular AMD (nAMD) treatment that we believe brolucizumab addresses. Full-Text PDF

The structure and functions of the choroid have been long acknowledged but the pathophysiology behind various anomalies has been difficult to understand until the advent of optical coherence tomography (OCT). With OCT imaging, choroidal cavitations appear as optically empty spaces between the outer retinal and choroidal layers with attenuation or loss of outer retinal layers. Choroidal cavitations are found in the posterior pole and seen in conditions such as pathologic myopia, north carolina macular dystrophy (NCMD), focal choroidal excavation (FCE), and torpedo maculopathy (TM). To date, these disorders have not been linked. A commonality they all share is malformation of the RPE-photoreceptor-choroid complex. The following report describes the differences and similarities of choroidal cavitation amongst the different retinal disorders and emphasizes the importance of multimodal imaging in the detection and management of potential complications.

Purpose To review the current therapeutic options for the management of diabetic retinopathy (DR) and diabetic macular edema (DME) and examine the evidence for integration of laser and pharmacotherapy. Methods A review of the PubMed database was performed using the search terms diabetic retinopathy, diabetic macular edema, neovascularization, laser photocoagulation, intravitreal injection, vascular endothelial growth factor (VEGF), vitrectomy, pars plana vitreous surgery, antiangiogenic therapy. With additional cross-referencing, this yielded 835 publications of which 301 were selected based on content and relevance. Results Many recent studies have evaluated the pharmacological, laser and surgical therapeutic strategies for the treatment and prevention of DR and DME. Several newer diagnostic systems such as optical coherence tomography (OCT), microperimetry, and multifocal electroretinography (mfERG) are also assisting in further refinements in the staging and classification of DR and DME. Pharmacological therapies for both DR and DME include both systemic and ocular agents. Systemic agents that promote intensive glycemic control, control of dyslipidemia and antagonists of the renin-angiotensin system demonstrate beneficial effects for both DR and DME. Ocular therapies include anti-VEGF agents, corticosteroids and nonsteroidal anti-inflammatory drugs. Laser therapy, both as panretinal and focal or grid applications continue to be employed in management of DR and DME. Refinements in laser devices have yielded more tissue-sparing (subthreshold) modes in which many of the benefits of conventional continuous wave (CW) lasers can be obtained without the adverse side effects. Recent attempts to lessen the burden of anti-VEGF injections by integrating laser therapy have met with mixed results. Increasingly, vitreoretinal surgical techniques are employed for less advanced stages of DR and DME. The development and use of smaller gauge instrumentation and advanced anesthesia agents have been associated with a trend toward earlier surgical intervention for diabetic retinopathy. Several novel drug delivery strategies are currently being examined with the goal of decreasing the therapeutic burden of monthly intravitreal injections. These fall into one of the five categories: non-biodegradable polymeric drug delivery systems, biodegradable polymeric drug delivery systems, nanoparticle-based drug delivery systems, ocular injection devices and with sustained release refillable devices. At present, there remains no one single strategy for the management of the particular stages of DR and DME as there are many options that have not been rigorously tested through large, randomized, controlled clinical trials. Conclusion Pharmacotherapy, both ocular and systemic, will be the primary mode of intervention in the management of DR and DME in many cases when cost and treatment burden are less constrained. Conventional laser therapy has become a secondary intervention in these instances, but remains a first-line option when cost and treatment burden are more constrained. Results with subthreshold laser appear promising but will require more rigorous study to establish its role as adjunctive therapy. Evidence to support an optimal integration of the various treatment options is lacking. Central to the widespread adoption of any therapeutic regimen for DR and DME is substantiation of safety, efficacy, and cost-effectiveness by a body of sound clinical trials.