Update on "Cell Therapy" Clinics Offering Treatments of Ocular Conditions Using Direct-To-Consumer Marketing Websites in the U.S.

PURPOSE: To assess the scope of U.S.-based companies advertising and administering non-Federal Drug Administration (FDA) approved cell-based therapy (herein called NFACT) for ocular conditions based on information from companies' public websites after the FDA's legal actions against specific NFACT clinics in 2018 and 2019. Current findings are compared to previously published data from 2017. DESIGN: Trend study looking at U.S.-based companies that use direct-to-consumer marketing and have websites advertising therapy for ocular conditions. METHODS: A systematic and extensive keyword-based Internet search was utilized to identify, document, and analyze U.S. business websites offering NFACT for ocular conditions as of August 2022. Main outcomes measured include, clinic locations, marketed ocular conditions, types of NFACT offered, source of stem cells used, routes of administration, and treatment costs. RESULTS: From the prior analysis in 2017 to the 2019 analysis, there was a decrease in the number of NFACT clinics from 76 to 62 and companies from 40 to 39. Given the concerning persistence of NFACTs in August 2019 an additional analysis was performed in 2022 which showed a drastic decrease in NFACT clinics from 62 in 2019 to 18 in 2023 and from 39 companies to 13 in 2023. In both 2019 and 2022, the most commonly referenced ocular condition was age-related macular degeneration (2019 - 72%, 2022 - 92%). The state with the most clinics was in Texas (2019 - 12; 2022 - 5). Autologous adipose-derived stem cells were the most common cell type used in both analyses. CONCLUSIONS: In 2019 U.S.-based direct-to-consumer companies marketing NFACT persisted despite (1) a lack of high-quality clinical evidence supporting the efficacy of these procedures, (2) the association of some of these treatments with severe vision loss, and (3) increasing FDA oversight and recent legal action. In 2022 the number of clinics and companies decreased, but their persistence is a reminder that continued concern is necessary and ophthalmic associations need to continue advocacy efforts to protect patients from these potentially predatory organizations.

OUTCOMES OF INFECTIOUS PANUVEITIS ASSOCIATED WITH SIMULTANEOUS MULTI-POSITIVE OCULAR FLUID POLYMERASE CHAIN REACTION.

PURPOSE: To evaluate features of infectious panuveitis associated with multiple pathogens detected by ocular fluid sampling. METHODS: Single-center, retrospective, consecutive case series of patients with aqueous/vitreous polymerase chain reaction testing with >1 positive result in a single sample from 2001 to 2021. RESULTS: Of 1,588 polymerase chain reaction samples, 28 (1.76%) were positive for two pathogens. Most common pathogens were cytomegalovirus (n = 16, 57.1%) and Epstein-Barr virus (n = 13, 46.4%), followed by varicella zoster virus (n = 8, 28.6%), Toxoplasma gondii (n = 6, 21.4%), herpes simplex virus 2 (n = 6, 21.4%), herpes simplex virus 1 (n = 6, 21.4%), and Toxocara (n = 1, 3.6%). Mean initial and final visual acuity (logarithm of the minimum angle of resolution) were 1.3 ± 0.9 (Snellen ∼20/400) and 1.3 ± 1.1 (Snellen ∼20/400), respectively. Cytomegalovirus-positive eyes (n = 16, 61.5%) had a mean final visual acuity of 0.94 ± 1.1 (Snellen ∼20/175), whereas cytomegalovirus-negative eyes (n = 10, 38%) had a final visual acuity of 1.82 ± 1.0 (Snellen ∼20/1,320) ( P < 0.05). Main clinical features included intraocular inflammation (100%), retinal whitening (84.6%), immunosuppression (65.4%), retinal hemorrhage (38.5%), and retinal detachment (34.6%). CONCLUSION: Cytomegalovirus or Epstein-Barr virus were common unique pathogens identified in multi-PCR-positive samples. Most patients with co-infection were immunosuppressed with a high rate of retinal detachment and poor final visual acuity. Cytomegalovirus-positive eyes had better visual outcomes compared with cytomegalovirus-negative eyes.

Vitreous metastasis from cutaneous melanoma: diagnosis and management / Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

Orbital Gas after 25-Gauge Pars Plana Vitrectomy with Incorrect Gas Mixture.

We present 2 cases of sutureless 25-gauge pars plana vitrectomy and fluid-gas exchange, in which incorrect gas concentrations likely led to elevated intraocular pressures and retrobulbar gas. Combined removal of orbital gas with anterior orbitotomy and pars plana vitrectomy was performed in the first case to address expanding intraocular and retrobulbar gas resulting from a suspected error in gas dilution. Vitreous and orbital gas removal by needling was effective in the second case. In patients with elevated intraocular pressure and orbital gas accumulation after vitrectomy, combined intraocular and orbital decompressions were effective in optimizing clinical outcomes. There is no consensus regarding the best management of orbital gas after vitrectomy. We propose that a multidisciplinary technique should be considered, when available.

INTRAOCULAR INFLAMMATION INCIDENCE AFTER INTRAVITREAL BROLUCIZUMAB INJECTION FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We evaluated the clinical outcomes of intraocular inflammation (IOI) of eyes with neovascular age-related macular degeneration (AMD) injected with brolucizumab in our tertiary referral center. METHODS: A retrospective case series for which clinical records of all eyes that received intravitreal brolucizumab at Bascom Palmer Eye Institute between December 1, 2019, and April 1, 2021, were reviewed. RESULTS: There were 345 eyes of 278 patients who received 801 brolucizumab injections. IOI was detected in 16 eyes of 13 patients (4.6%). In those patients, baseline Logarithm of Minimu Angle of Resolution (logMAR) best-corrected visual acuity was 0.32 0.2 (20/42), while it was 0.58 0.3 (20/76) at IOI presentation. The mean number of injections among eyes experiencing IOI was 2.4, and the interval between the last brolucizumab injection and IOI presentation was 20 days. There was no known case of retinal vasculitis. Management of IOI included topical steroids in seven eyes (54%), topical and systemic steroids in five eyes (38%), and observation in one eye (8%). Best-corrected visual acuity returned to baseline and inflammation resolved in all eyes by the last follow-up examination. CONCLUSION: Intraocular inflammation after brolucizumab injection for neovascular AMD was not uncommon. Inflammation resolved in all eyes by the last follow-up visit.

Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for Primary Open-Angle Glaucoma: Safety, Neuroprotection, and Neuroenhancement.

Purpose: To assess the safety and efficacy of a ciliary neurotrophic factor (CNTF) intraocular implant on neuroprotection and neuroenhancement in glaucoma. Design: Open-label, prospective, phase I clinical trial. Participants: A total of 11 participants were diagnosed with primary open-angle glaucoma (POAG). One eye of each patient was assigned as the study (implant) eye. Methods: The study eye was implanted with a high-dose CNTF-secreting NT-501 implant, whereas the other eye served as a control. All patients were followed up for 18 months. Analysis was limited to descriptive statistics. Main Outcome Measures: Primary outcome was safety through 18 months after implantation assessed by serial eye examinations, structural and functional testing, and adverse events (AEs) recording. Parameters measured included visual acuity (VA), Humphrey visual field (HVF), pattern electroretinogram, scanning laser polarimetry with variable corneal compensation (GDx VCC), and OCT. These parameters were also used for secondary analysis of efficacy outcome. Results: All NT-501 implants were well tolerated with no serious AEs associated with the implant. The majority of AEs were related to the implant placement procedure and were resolved by 12 weeks after surgery. Foreign-body sensation was the most commonly reported AE and was self-limited to the postoperative period. The most common implant-related AE was pupil miosis; no patients underwent explant. Visual acuity and contrast sensitivity decreased more in fellow eyes than in study eyes (VA, -5.82 vs. -0.82 letters; and contrast sensitivity, -1.82 vs. -0.37 letters, for fellow vs. study eyes, respectively). The median HVF visual field index and mean deviation measurements worsened (decreased) in fellow eyes (-13.0%, -3.9 dB) and improved (increased) in study eyes (2.7%, 1.2 dB). Implanted eyes showed an increase in retinal nerve fiber layer thickness measured by OCT and by GDx VCC (OCT, 2.66 µm vs. 10.16 µm; and GDx VCC, 1.58 µm vs. 8.36 µm in fellow vs. study eyes, respectively). Conclusions: The NT-501 CNTF implant was safe and well tolerated in eyes with POAG. Eyes with the implant demonstrated both structural and functional improvements suggesting biological activity, supporting the premise for a randomized phase II clinical trial of single and dual NT-501 CNTF implants in patients with POAG, which is now underway. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Vision health perspectives on Breaking Bad: Ophthalmic sequelae of methamphetamine use disorder.

Methamphetamine use has become a rampant public health issue that not only causes devastating consequences to the user but also poses a burden to surrounding communities. A spectrum of ophthalmic sequelae is associated with methamphetamine use and includes episcleritis, scleritis, corneal ulceration, panophthalmitis, endophthalmitis, retinal vasculitis, and retinopathy. In many instances, prompt recognition of the condition and associated infectious process and early initiation of antimicrobial therapy are crucial steps to preventing vision loss. In this review, we summarize the reported ocular complications that may result from methamphetamine use in addition to several postulated mechanisms regarding the ocular toxicity of methamphetamine. The increasing prevalence of methamphetamine use as a public health threat highlights the need for continued investigation of this ophthalmologic issue.

Pars Plana Vitrectomy for Retained Lens Fragments After Cataract Surgery: Outcomes Based on Timing of Surgery.

Purpose: To evaluate the outcomes and complications in patients with retained lens fragments (RLF) after cataract surgery, comparing those who received pars plana vitrectomy (PPV) on the same day, within 1 week, or later than 1 week after cataract surgery. Patients and Methods: Retrospective case series of all patients who underwent PPV for RLF at Bascom Palmer Eye Institute between January 1, 2012 and September 30, 2020. Individuals with less than 3 months of follow-up, chronic uveitis, congenital cataract, previtrectomy retinal detachment (RD), and severe trauma were excluded. All analyses for categorical and binary variables used chi-squared tests. Analyses for continuous variables were performed using multivariate analyses of covariance, adjusting for differences in baseline visual acuity before cataract surgery. Results: The study included 246 eyes of 246 patients. The timing distribution included the following: 140 (57%) eyes underwent same-day PPV, 33 (13%) eyes underwent same-week PPV, and 73 (30%) eyes underwent PPV after 1 week (up to 90 days). When all eyes were included in analysis, there were no statistically significant differences in mean best-corrected visual acuity (BCVA) between groups at last follow-up examination (P = 0.07). When only eyes without known pre-existing ocular disease (N = 157) were included in analysis, there were no differences in mean BCVA between groups at all postoperative timepoints (P > 0.05). The rate of RD did not differ between groups when eyes with and without pre-existing ocular disease were analyzed (P > 0.05). Conclusion: In the current study, there were no statistically significant differences in postoperative BCVA or rates of RD at last follow-up examination in eyes undergoing PPV for RLF on the same day, within 1 week, or later than 1 week after cataract surgery.

Suprachoroidal Injection of Triamcinolone Acetonide Injectable Suspension for the Treatment of Macular Edema Associated With Uveitis in the United States: A Cost-Effectiveness Analysis.

OBJECTIVES: Suprachoroidal injection of triamcinolone acetonide is the first Food and Drug Administration-approved treatment for macular edema associated with uveitis. A cost-effectiveness analysis was performed comparing this treatment with best supportive care (BSC) for the management of this indication from US Medicare and commercial payer perspectives. METHODS: A patient-level simulation was developed per the patient characteristics and changes in best-corrected visual acuity letter scores observed in a phase III study of triamcinolone acetonide (PEACHTREE). The wholesale acquisition cost of triamcinolone acetonide was $1650/injection; suprachoroidal injection cost was assumed at $200/injection. Healthcare costs were informed by a US claims-based analysis. Mortality risk associated with severe vision loss and blindness was modeled by applying a hazard ratio to all-cause mortality rates of the US general population. Health-related quality of life weights, obtained from a regression model fitted to the Visual Function Questionnaire-25 data from PEACHTREE, were applied based on the best-corrected visual acuity scores of both eyes. Costs (2020 US dollar) and benefits were discounted at 3% annually. Incremental cost-effectiveness ratios were estimated over a 10-year horizon. RESULTS: In the base-case, the incremental cost-effectiveness ratio comparing triamcinolone acetonide with BSC was $28 479 per quality-adjusted life-year gained. The wholesale acquisition cost for triamcinolone acetonide for suprachoroidal use was ∼68%, ∼56%, and ∼27% below the willingness-to-pay thresholds of $150 000, $100 000, and $50 000 per quality-adjusted life-year gained, respectively. Results were robust in sensitivity and scenario analyses. CONCLUSIONS: Triamcinolone acetonide for suprachoroidal use is cost-effective compared with BSC for patients with macular edema associated with uveitis.

Surgical Outcomes of Acute Retinal Necrosis-Related Retinal Detachment in Polymerase Chain Reaction-Positive Patients: A Single-Center Experience.

PURPOSE: To evaluate the clinical features, operative techniques, and surgical outcomes of patients who underwent surgery for acute retinal necrosis (ARN)-related retinal detachment (RD). DESIGN: Retrospective, longitudinal, consecutive case series. PARTICIPANTS: Patients with polymerase chain reaction-positive ARN presenting from 2011 to 2021 who underwent vitreoretinal surgery for ARN-related RD at our institution. METHODS: Univariate, multivariate, and survival analyses were used to determine predictors of anatomic and functional outcomes. MAIN OUTCOME MEASURES: Single-surgery anatomic success rate, recurrent RD, and visual acuity (VA) at 1 year. RESULTS: Thirty-four eyes of 34 patients (32.4% women, mean age, 45.1 ± 20.4 years) were included for analysis with a median follow-up of 2.5 years (interquartile range [IQR], 0.8-5.5 years). Presenting VA was 1.1 ± 0.8 logarithm of the minimum angle of resolution (LogMAR) (Snellen ∼20/250). The median time from presentation to RD surgery was 1.7 months (IQR, 0.8-4.1 months), and the mean preoperative VA was 1.6 ± 0.8 LogMAR (Snellen ∼20/800). Small-gauge pars plana vitrectomy (PPV) with or without a scleral buckle (SB) was performed for all eyes with an overall single-surgery success rate of 63.6%, with no statistically significant differences in visual/anatomic outcomes between PPV and PPV/SB cases. Silicone oil was used for tamponade in 33 (97.1%) cases and was removed in 10 (30.3%) with good anatomic and final functional outcomes (Snellen âˆ¼20/80). Independent predictors of recurrent RD included the female sex (hazard ratio, 8.38; 95% confidence interval, 2.03-34.68; P < 0.01) and zone 1 retinitis involvement at presentation (hazard ratio, 10.95; 95% confidence interval, 2.12-56.48; P < 0.01). The mean VA at 1 year (VA1year) and at the final follow-up both had a Snellen equivalent of 20/640 (P > 0.05 for both compared with preoperative VA, respectively). Eyes that achieved single-surgery success had VA1year of 20/200 versus hand movements in those with single-surgery failure (P < 0.01). On multivariate linear regression, younger age (P = 0.04) and better presenting VA (P < 0.01) were both associated with better VA1year. CONCLUSIONS: Moderate single-surgery anatomic success can be achieved with modern vitreoretinal surgical techniques for ARN-related RD, although visual outcomes remain poor. Further studies investigating interventions for increasing single-surgery success rates, for the inflammatory complications of ARN, and for preventing ARN-related RD are needed.

Salmon patch-associated vitreous hemorrhage in non-proliferative sickle cell retinopathy masquerading as infectious uveitis.

PURPOSE: To report three cases of non-proliferative sickle cell retinopathy (NPSR) with vitreous hemorrhage masquerading as infectious uveitis. OBSERVATIONS: Three patients were referred from ophthalmologists to our practices with clinical findings suggestive of infectious uveitis. The first patient was referred for new-onset floaters in both eyes, bilateral vitritis and dome-shaped lesions on B-scan ultrasound. He was initially treated for tuberculosis uveitis due to a positive purified protein derivative test. The second patient was referred with floaters and hazy vision in the setting of recent fever and headache and was also reported to have vitritis and unilateral yellow vitreoretinal lesions on fundoscopy. She was initially treated for toxoplasmosis and endogenous endophthalmitis. The third patient presented with flashes, floaters, and decreased vision four months after a ring-enhancing lesion was found on brain imaging, and was found to have unilateral vitritis with yellow vitreoretinal lesions. He was initially started on topical steroids and cycloplegics empirically for uveitis. All patients were ultimately diagnosed as having manifestations of NPSR, including vitreous hemorrhage, and dehemoglobinized salmon patch hemorrhages. CONCLUSIONS AND IMPORTANCE: NPSR can occasionally masquerade as infectious uveitis. Obtaining a detailed history with relevant ancillary testing, along with performing a careful physical exam to recognize important clues, can help the physician arrive at the correct diagnosis in these equivocal cases.

Ocular and Systemic Complications of COVID-19: Impact on Patients and Healthcare.

There is increasing information available about the effects of the SARS-CoV-2 virus on the systemic and ocular health of patients, as well as the effects of delayed health care. This mini-review summarizes the potential complications and treatments of COVID-19. Systemic findings include respiratory illness, risk of thromboembolic events, and neurologic findings. Some patients may develop persistent symptoms even after the infection resolves. Effective treatment options include glucocorticoids, antivirals, interleukin-6 antagonists, monoclonal antibodies, Janus kinase inhibitors and vaccines. Potential ocular findings of COVID-19 include conjunctivitis, cranial nerve palsies, and microvascular changes in the retina; most symptoms resolved over time. During the lockdown periods, teleophthalmology was utilized to triage non-urgent issues; patients who did present to emergency departments tended to have more severe disease with worse visual prognoses. While transient delays in outpatient ophthalmic care may be tolerated in some patients, others experienced significant vision loss with interruptions in treatments. Resumption of ophthalmic care as soon as possible may help mitigate the effects of delayed care due to the pandemic.

Clinical Characteristics and Outcomes of Eyes with Intraocular Inflammation after Brolucizumab: Post Hoc Analysis of HAWK and HARRIER.

PURPOSE: This analysis of the pivotal phase 3 HAWK and HARRIER trials aimed to provide insights on the timing of presentation, management, and outcomes of intraocular inflammation (IOI)-related adverse events (AEs), as reported by investigators in these trials. DESIGN: Post hoc analysis of investigator-reported IOI-related AEs in HAWK and HARRIER. PARTICIPANTS: Of 1088 brolucizumab-treated eyes (3 or 6 mg), 49 eyes demonstrated at least 1 IOI-related AE and were included in this analysis. METHODS: Reports of IOI-related AEs were analyzed and descriptive statistics were provided for outcome measures. MAIN OUTCOME MEASURES: Incidence and description of eyes with IOI-related AEs, timing of presentation, management, clinical outcomes, and brolucizumab treatment after the first IOI-related AE. RESULTS: Seventy IOI-related AEs were reported in 49 eyes. Before the onset of first IOI-related AE, eyes received a mean ± standard deviation (SD) of 3.9 ± 2.2 brolucizumab injections. Median time to first IOI-related AE from the last administered brolucizumab injection was 18.0 days (interquartile range, 4.0-29.0 days). Of the 70 AEs, 61 (87.1%) were treated, most with topical corticosteroids; systemic and intraocular corticosteroids were used for 3 AEs each. Overall, inflammation resolved completely in 39 eyes (79.6%), resolved with sequelae in 5 eyes (10.2%), and did not resolve in 5 eyes (10.2%) by end-of-study (EOS). Overall, the mean ± SD best-corrected visual acuity (BCVA) change from baseline to EOS, before AE to the lowest BCVA in 3 months after AE, and from before AE to EOS were -0.84 ± 20.6 , -16.31 ± 17.6, and -0.22 ± 18.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, respectively. Of the 36 eyes (73.5%) that continued with brolucizumab therapy after the first IOI-related AE, 24 completed the trials and 12 discontinued; mean ± SD BCVA change in these eyes was 2.6 ± 17.6, 7.8 ± 13.2, and -7.7 ± 21.3 ETDRS letters, respectively, from baseline to EOS. The remaining 13 eyes (26.5%) were not treated with brolucizumab after first IOI-related AE and showed a mean ± SD BCVA change of -10.4 ± 25.5 ETDRS letters from baseline to EOS. CONCLUSIONS: Findings of this analysis highlight the need for continued vigilance and monitoring for any signs of IOI-related events in patients receiving brolucizumab.

Safety Outcomes of Brolucizumab in Neovascular Age-Related Macular Degeneration: Results From the IRIS Registry and Komodo Healthcare Map.

IMPORTANCE: Limited data exist on the real-world safety outcomes of patients with neovascular age-related macular degeneration treated with brolucizumab (Beovu). OBJECTIVE: To determine the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent brolucizumab treatment. Additionally, potential risk factors associated with these adverse events were evaluated. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with neovascular age-related macular degeneration in the Intelligent Research in Sight (IRIS) Registry and Komodo Healthcare Map. Patients initiating and receiving 1 or more brolucizumab injections from October 8, 2019, to June 5, 2020, with up to 6 months of follow-up were included. INTERVENTION: Brolucizumab injections. MAIN OUTCOME AND MEASURES: Incidence of IOI (including RV) and/or RO and RV and/or RO and risk stratification for the identified risk factors. RESULTS: Of 10 654 and 11 161 included eyes (from the IRIS Registry and Komodo Health database, respectively), the median follow-up times were 97 and 95 days. Most eyes switched from another anti-vascular endothelial growth factor agent (9686 of 10 654 [90.9%] and 10 487 of 11 161 [94.0%], respectively), most commonly aflibercept (7160 of 9686 [73.9%] and 7156 of 10 487 [68.2%]), and most were from women (6105 of 10 654 [57.3%] and 6452 of 11 161 [57.8%]). The overall incidence of IOI and/or RO was 2.4% (255 of 10 654 eyes) and 2.4% (268 of 11 161 eyes) for the IRIS and Komodo groups, respectively, and RV and/or RO, 0.6% (59 of 10 654 eyes and 63 of 11 161 eyes), respectively. Patients with a history of IOI and/or RO in the 12 months before brolucizumab initiation had an increased observed risk rate (8.7% [95% CI, 6.0%-11.4%] and 10.6% [95% CI, 7.5%-13.7%]) for an IOI and/or RO event in the 6 months following the first brolucizumab treatment compared with patients without prior IOI and/or RO (2.0% in both data sets). There was an increased estimated incidence rate in women (2.9% [95% CI, 2.5%-3.3%] and 3.0% [95% CI, 2.6%-3.4%]) compared with men (1.3% [95% CI, 1.0%-1.7%] and 1.4% [95% CI, 1.0%-1.7%]), but this risk was not as large as that of a prior IOI and/or RO. Similar findings were observed for patients with RV and/or RO events. CONCLUSIONS AND RELEVANCE: The incidence rate of IOI and/or RO was approximately 2.4%. Patient eyes with IOI and/or RO in the 12 months prior to first brolucizumab injection had the highest observed risk rate for IOI and/or RO in the early months after the first brolucizumab treatment. However, given study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events, and causality with brolucizumab cannot be assessed.

Peripapillary Halo in Inflammatory Papillitis of Birdshot Chorioretinopathy.

PURPOSE: Peripapillary halos (PPH) are peripapillary changes observed surrounding the optic nerve head in normal eyes and eyes with different disorders. Recognizing the microstructure and mechanism of development of these halos will help clinicians understand the different associated retinal and optic nerve head pathologies. We describe the in vivo histological characteristics of PPH in birdshot chorioretinopathy (BSCR). PATIENTS AND METHODS: This was a prospective observational case-series in a single tertiary referral center. Six eyes of three patients with PPH associated with BSCR were determined through clinical examination, fundus photography, and fundus autofluorescence (FAF). Patients underwent swept-source optical coherence tomography (SS-OCT) imaging of the optic nerve head and peripapillary region. RESULTS: In SS-OCT B-scans across the area of PPH, we observed thinning and interruption of retinal pigment epithelium (RPE)-Bruch's membrane complex. These halos are a circumferential form of alpha zone RPE-associated crescentic peripapillary atrophy (PPA), unlike the PPH observed with myopia and normal aging. CONCLUSION: PPH in BSCR patients may be a sign of prior inflammatory optic neuropathy.

Drug-related adverse effects of antivascular endothelial growth factor agents.

PURPOSE OF REVIEW: Antivascular endothelial growth factor (VEGF) agents have provided historic therapeutic breakthroughs in the treatment of retinal disease. New anti-VEGF agents are emerging for the treatment of retinal vascular diseases. Both systemic and ocular adverse effect need to be understood in managing patients. This review aims to highlight the adverse effects seen with routine use of bevacizumab, ranibizumab and aflibercept, as well as with new medications such as brolucizumab and abicipar. RECENT FINDINGS: We review the recent findings of intraocular inflammation (IOI) of brolucizumab and abicipar in the context of the efficacy and safety reported with the routine anti-VEGF agents. Specifically, brolucizumab has been reported to cause occlusive retinal vasculitis in the setting of IOI, which has not been seen in other anti-VEGF medications. In addition, abicipar appears to cause IOI at a higher rate of patients than other anti-VEGF agents have previously. SUMMARY: Newer anti-VEGF agents pose a significant risk of adverse events not seen with routine anti-VEGF agents.