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Journal Club – 1403.07.15

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Real World Experience with Intravitreal Pegcetacoplan for Treating Advanced Atrophic Age-Related Macular Degeneration

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Journal Club 4-10-2021

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Characterizing New-Onset Exudation in the Randomized Phase 2 FILLY Trial of Complement Inhibitor Pegcetacoplan for Geographic Atrophy

Charles C Wykoff, Philip J Rosenfeld, Nadia K Waheed, Rishi P Singh, Nick Ronca, Jason S Slakter, Giovanni Staurenghi, Jordi Monés, Caroline R Baumal, Namrata Saroj, Ravi Metlapally, Ramiro Ribeiro

Free article

Abstract

Objective: Evaluate clinical characteristics of eyes that developed investigator-determined new-onset exudative age-related macular degeneration (eAMD) during the FILLY trial.

Design: Post-hoc analysis of the phase 2 study of intravitreal pegcetacoplan in geographic atrophy (GA).

Subjects: ۲۴۶ subjects with GA secondary to AMD.

Intervention: Either 15 mg intravitreal pegcetacoplan or sham given monthly or every other month (EOM) for 12 months followed by a 6-month off-treatment period.

Main outcome measures: Time of onset of new eAMD in the study eye; history of eAMD in the fellow eye; presence of double layer sign (DLS) on structural optical coherence tomography (OCT) in the study eye; changes in retinal anatomy by structural OCT and fluorescein angiography (FA); and changes in visual acuity.

Results: Exudation was reported in 26 study eyes across all treatment groups over 18 months. Mean time to diagnosis of eAMD was 256 days (range: 31 to 555). Overall, a higher proportion of subjects with a history of eAMD in the fellow eye (P=0.016) and a DLS in the study eye at baseline (P=0.0001) developed eAMD. Among study eyes that developed eAMD, 18/26 (69%) had a history of fellow eye eAMD and 19/26 (73.1%) had a DLS at baseline, compared to 72/217 (33%) (P=0.0003) and 70/215 (32.5%) (P<0.0001)respectively, of study eyes that did not develop eAMD. All 21 subjects with structural OCT imaging at the time of eAMD diagnosis had subretinal fluid and/or intraretinal cysts, consistent with exudation. Among 17 subjects who received FA at the time of eAMD diagnosis, 10 had detectable MNV, all occult lesions. Development of eAMD did not appear to have an appreciable impact on visual acuity, and all subjects responded to anti-VEGF therapy.

Conclusions: Intravitreal injections of pegcetacoplan slowed the rate of GA growth and were associated with an unexpected dose-dependent increased incidence of eAMD with no temporal clustering of onset. eAMD appeared to be associated with the presence of baseline eAMD in the contralateral eye and a DLS, suggestive of nonexudative MNV, in the study eye. The safety profile of pegcetacoplan was acceptable to proceed to phase 3 studies without adjustments to enrollment criteria.

Retinopathy of transcobalamin II deficiency: long-term stability with treatment

Sarah Chorfi ۱, Grant A Mitchell ۲, Cynthia X Qian ۱Affiliations expandPMID: ۳۳۴۷۶۶۴۵

DOI: ۱۰.۱۰۱۶/j.ophtha.2021.01.015

COVID-19 and Use of Teleophthalmology (CUT Group): Trends and Diagnoses

David S Portney ۱, Ziwei Zhu ۲, Evan M Chen ۳, Emma Steppe ۲, Priyanka Chilakamarri ۴, Maria A Woodward ۵, Chad Ellimoottil ۶, Ravi Parikh ۷Affiliations expand

Fundus Pigmentation in the Diagnosis and Treatment of Retinopathy of Prematurity

Kenneth C Fan ۱, Sarah P Read ۲, Nimesh A Patel ۱, Elizabeth A Vanner ۱, Hasenin Al-Khersan ۱, Diana M Laura ۱, Parastou Pakravan ۱, Catherin I Negron ۱, Audina M Berrocal ۳Affiliations expand

Patient Harm due to Diagnostic Error of Neuro-Ophthalmologic Conditions

Leanne Stunkel ۱, Rahul A Sharma ۲, Devin D Mackay ۳, Bradley Wilson ۴, Gregory P Van Stavern ۱, Nancy J Newman ۵, Valérie Biousse ۶Affiliations expand

Abstract

Objective: To prospectively examine diagnostic error of neuro-ophthalmic conditions and resultant harm at multiple sites.

Design: Prospective cross-sectional study.

Subjects: ۴۹۶ consecutive adult new patients seen at three university-based neuro-ophthalmology clinics in the United States in 2019-2020.

Methods: Collected data regarding demographics, prior care, referral diagnosis, final diagnosis, diagnostic testing, treatment, patient disposition, and impact of the neuro-ophthalmologic encounter. For misdiagnosed patients, we identified the cause of error using the Diagnosis Error Evaluation and Research (DEER) taxonomy tool, and whether the patient suffered harm due to the misdiagnosis.

Main outcome measures: The primary outcome was whether patients who were misdiagnosed prior to neuro-ophthalmology referral suffered harm as a result of the misdiagnosis. Secondary outcomes included appropriateness of referrals, misdiagnosis rate, interventions undergone prior to referral, and the primary type of diagnostic error.

Results: Referral diagnosis was incorrect in 49% of cases. Misdiagnosed patients suffered harm in 26%, which could have been prevented by earlier referral to neuro-ophthalmology in 97%. Patients experienced inappropriate laboratory testing, diagnostic imaging, or treatment prior to referral in 23%, with higher rates for patients misdiagnosed prior to referral (34% of patients compared to 13% with a correct referral diagnosis, p<0.0001). Seventy-six percent of inappropriate referrals were misdiagnosed, compared to 45% of appropriate referrals (p<0.0001). The most common reasons for referral were optic neuritis or optic neuropathy (21%), papilledema (18%), diplopia or cranial nerve palsies (16%), and unspecified vision loss (11%). The most common sources of diagnostic error were the physical examination (36%), generation of a complete differential diagnosis (24%), history taking (24%), and utilization or interpretation of diagnostic testing (13%). In 489/496 (99%) patients, neuro-ophthalmologic consultation impacted patient care. In 2% of cases, neuro-ophthalmology directly saved the patient’s life or vision, in an additional 10% harmful treatment was avoided or appropriate urgent referral was provided, and in an additional 48% neuro-ophthalmology provided a diagnosis and direction to the patient’s care.

Conclusions: Misdiagnosis of neuro-ophthalmic conditions, mismanagement prior to referral, and preventable harm are common. Early appropriate referral to neuro-ophthalmology may prevent patient harm.

Comparison of the myopic progression before, during and after COVID-19 lockdown

Pingjun Chang ۱, Bing Zhang ۱, Li Lin ۱, Ruru Chen ۱, Siping Chen ۱, Yune Zhao ۲, Jia Qu ۳Affiliations expand

Health and Vision-Related Quality of Life in a Randomized Controlled Trial Comparing Methotrexate and Mycophenolate Mofetil for Uveitis

Nicole K Kelly ۱, Aheli Chattopadhyay ۱, S R Rathinam ۲, John A Gonzales ۳, Radhika Thundikandy ۲, Anuradha Kanakath ۴, S Bala Murugan ۵, R Vedhanayaki ۲, Dean Cugley ۶, Lyndell L Lim ۶, Eric B Suhler ۷, Hassan A Al-Dhibi ۸, Caleb D Ebert ۱, Elyse J Berlinberg ۱, Travis C Porco ۹, Nisha R Acharya ۱۰, FAST Research GroupAffiliations expand

Abstract

Objective: To evaluate changes in health-related and vision-related quality of life (QoL) among patients with noninfectious uveitis who were treated with antimetabolites.

Design: Secondary analysis of a randomized controlled trial.

Participants: Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico.

Methods: From 2013-2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in QoL were measured using Wilcoxon signed rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, sex, and site. Among Indian patients, vision-related QoL scores from a general scale (NEI-VFQ) and a culturally specific scale (IND-VFQ) were compared using Pearson correlation tests.

Main outcome measures: Vision-related (NEI-VFQ and IND-VFQ) and health-related (PCS (physical component score) and MCS (mental component score) SF-36v2) QoL was measured at baseline, the primary endpoint (6 months or treatment failure before 6 months), and the secondary endpoint (12 months or treatment failure between 6-12 months).

Results: Among 193 participants who reached the primary endpoint, vision-related QoL increased from baseline by a median of 12.0 points (interquartile range (IQR)=1.0-26.1, NEI-VFQ scale), physical health-related QoL increased by a median of 3.6 points (IQR=-1.4-14.9, PCS SF-36v2), and mental health-related QoL increased by a median of 3.0 points (IQR=-3.7-11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores were all significant (p<0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; p > 0.05 for all). NEI-VFQ and IND-VFQ scores for Indian participants were highly correlated at baseline and the primary and secondary endpoints (correlation coefficient=0.87, 0.80, 0.90, respectively).

Conclusions: Among patients treated with methotrexate or mycophenolate mofetil for uveitis, vision-related and health-related QoL significantly improved over the course of one year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning.