Showing papers by "Allen C. Ho published in 2022"

Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial

Abstract: CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 ( NCT03140969 ), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit-risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development.

American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry and the IRIS Registry Analytic Center Consortium

Abstract: The American Academy of Ophthalmology (AAO) Intelligent Research in Sight (IRIS®) Registry is the nation’s first centralized and the world’s largest medical specialty registry.1American Academy of OphthalmologyIRIS Registry.https://www.aao.org/iris-registryGoogle Scholar The IRIS Registry database was established in 2014 and currently includes selected de-identified electronic health record data from thousands of participating ophthalmologists and allied eye care providers across the United States. The data are automatically uploaded to the IRIS Registry, in most cases via systems integration software, and include patient demographics, patient medical and ocular history, clinical examination findings, diagnoses, procedures, and medications.2American Academy of OphthalmologyAmerican Academy of Ophthalmology IRIS Registry (Intelligent Research in Sight) analytics data dictionary.https://www.aao.org/Assets/2bf5a8e9-07fc-43d6-952c-2c7a01d7d4e4/636759751222930000/v4-dd-10-23-2018-pdfDate: 2018Date accessed: July 2, 2021Google Scholar The origin of the IRIS Registry is based on previous AAO data collection initiatives that were part of a broader effort to provide routine clinical practice, evidence-based guidance for clinicians. With advances in electronic health record data collection and the development of other specialty-based clinical data registries, the AAO launched a task force in 2012 to explore the creation of an ophthalmic disease data registry.3Parke 2nd, D.W. Rich 3rd, W.L. Sommer A. Lum F. The American Academy of Ophthalmology’s IRIS® Registry (Intelligent Research in Sight clinical data): a look back and a look to the future.Ophthalmology. 2017; 124: 1572-1574Google Scholar At its initial launch in 2014, the registry collected data from 3000 clinicians throughout the United States, but the project has since expanded rapidly. As of October 2021, the IRIS Registry includes data on more than 412 million patient visits from more than 70.8 million unique patients, with nearly 16 000 eye clinicians reporting.4American Academy of OphthalmologyIRIS Registry data analysis.https://www.aao.org/iris-registry/data-analysis/requirementsGoogle Scholar Although estimates differ, approximately 70% of all 18 000 active practicing ophthalmologists in the United States are currently contributing to the IRIS Registry (Flora Lum, MD, personal communication, 2021). The goals for the IRIS Registry include creating both national and interpractice benchmark reports on best practices for improving patient care; assisting practices with meeting federal reporting requirements; enabling data analysis for population health, rare disease research, and new scientific discovery; and identifying safety signals in new drugs and devices. The IRIS Registry has already had a significant impact on clinical practice. For example, providers who use the IRIS Registry to demonstrate their compliance with required quality measures avoid penalties (an average of $36 156 per ophthalmologist for 2020) and can receive small bonuses (the top was $7191 per ophthalmologist in 2019) from the Centers for Medicare and Medicaid Services.3Parke 2nd, D.W. Rich 3rd, W.L. Sommer A. Lum F. The American Academy of Ophthalmology’s IRIS® Registry (Intelligent Research in Sight clinical data): a look back and a look to the future.Ophthalmology. 2017; 124: 1572-1574Google Scholar In addition, the IRIS Registry allows physicians to compare their performance with that of other clinicians (both in their own practice and nationally) and to improve patient outcomes.5Rich W.L. Chiang M.F. Lum F. et al.Performance rates measured in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight).Ophthalmology. 2018; 125: 782-784Google Scholar Clinician performance measures such as cataract surgery visual acuity outcomes were shown to have improved since the IRIS Registry began.5Rich W.L. Chiang M.F. Lum F. et al.Performance rates measured in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight).Ophthalmology. 2018; 125: 782-784Google Scholar Advancing scientific discovery has been another major goal of the IRIS Registry. In 2017, the AAO selected several academic centers with the capacity for big data analytics for the IRIS Registry Analytic Center Consortium through an application process. Researchers at these selected centers were allowed to develop research questions for consideration and were granted access to the IRIS Registry data in late 2019 that would allow in-house analytics instead of relying on the AAO or its affiliated team. After an application process, the University of Washington, Stanford University, Wills Eye Hospital/Thomas Jefferson University, and Massachusetts Eye and Ear/Harvard Ophthalmology were selected. Over several years, principal investigators in the IRIS Registry Analytic Center Consortium have worked together with the AAO leadership, the AAO Committee on IRIS Registry Analytics, and technology partners such as Verana Health to develop data abstraction methods for big data research approaches using the IRIS Registry data. To date, the Analytic Center Consortium has published more than 10 major studies in addition to numerous meeting abstracts and paper presentations.4American Academy of OphthalmologyIRIS Registry data analysis.https://www.aao.org/iris-registry/data-analysis/requirementsGoogle Scholar,6Lee C.S. Owen J.P. Yanagihara R.T. et al.Smoking is associated with higher IOP regardless of glaucoma, a retrospective study of 12.5 million patients using the IRIS® Registry.Ophthalmol Glaucoma. 2020; 3: 253-261Google Scholar, 7Lacy M. Kung T.-P.H. Owen J.P. et al.Endophthalmitis rate in immediately sequential versus delayed sequential bilateral cataract surgery within the Intelligent Research in Sight (IRIS) Registry data.Ophthalmology. 2021 Jul 13; S0161-6420 (00519-4) (Online ahead of print)https://doi.org/10.1016/j.ophtha.2021.07.008Google Scholar, 8Herrinton L.J. Liu L. Alexeeff S. et al.Immediate sequential vs. delayed sequential bilateral cataract surgery: retrospective comparison of postoperative visual outcomes.Ophthalmology. 2017; 124: 1126-1135Google Scholar, 9Anchouche S. Hall N. Bal S. et al.Chemical and thermal ocular burns in the United States: an IRIS Registry analysis.Ocul Surf. 2021; 21: 345-347Google Scholar, 10Bagdasarova Y. Lee A.Y. Maring M. et al.Cataract surgery is not associated with decreased risk of retinal vein occlusion.Ophthalmology Science. 2021; 1: 100041Google Scholar, 11Yang S.-A. Mitchell W.G. Hall N. et al.Usage patterns of minimally invasive glaucoma surgery (MIGS) differ by glaucoma type: IRIS Registry analysis 2013–2018.Ophthalmic Epidemiol. 2021 Jul 26; (Online ahead of print): 1-9https://doi.org/10.1080/09286586.2021.1955391Google Scholar, 12Li Y. Hall N.E. Pershing S. et al.Age, gender, and laterality of retinal vascular occlusion: a retrospective study from the IRIS® Registry.Ophthalmol Retina. 2021 May 12; S2468-6530 (Online ahead of print): 00163-00169https://doi.org/10.1016/j.oret.2021.05.004Google Scholar The AAO is currently executing the second phase of the IRIS Registry Analytic Center Consortium and has selected additional centers to join the consortium during this phase. Scientific discovery via IRIS Registry projects is not unique to the IRIS Registry Analytic Center Consortium because individual research projects are supported by foundations and subspecialty societies through available grants, such as the Research to Prevent Blindness and the AAO Award for IRIS Registry Research, the Hoskins Center IRIS Registry Research Fund, the Knights Templar Eye Foundation Pediatric Ophthalmology Fund, and the American Glaucoma Society IRIS Registry Grant Program.13Vanner E.A. Sun C.Q. McSoley M.J. et al.Tube Versus Trabeculectomy IRIS® Registry one-year composite outcome analysis with comparisons to the randomized controlled trial.Am J Ophthalmol. 2021; 227: 87-99Google Scholar, 14Olivier M.M.G. Smith O. Croteau-Chonka C.C. et al.Demographic and clinical characteristics associated with minimally invasive glaucoma surgery use: an IRIS® Registry retrospective cohort analysis.Ophthalmology. 2021; 128: 1292-1299Google Scholar, 15Chang T.C. Parrish R.K. Fujino D. et al.Factors associated with favorable laser trabeculoplasty response: IRIS Registry analysis.Am J Ophthalmol. 2021; 223: 149-158Google Scholar The Hoskins Center and Knights Templar Eye Foundation grants are earmarked for private practice ophthalmologists only. Several important analyses of IRIS Registry data have been published, covering a wide variety of topics such as usage patterns of minimally invasive glaucoma surgery,11Yang S.-A. Mitchell W.G. Hall N. et al.Usage patterns of minimally invasive glaucoma surgery (MIGS) differ by glaucoma type: IRIS Registry analysis 2013–2018.Ophthalmic Epidemiol. 2021 Jul 26; (Online ahead of print): 1-9https://doi.org/10.1080/09286586.2021.1955391Google Scholar long-term clinical outcomes in glaucoma,13Vanner E.A. Sun C.Q. McSoley M.J. et al.Tube Versus Trabeculectomy IRIS® Registry one-year composite outcome analysis with comparisons to the randomized controlled trial.Am J Ophthalmol. 2021; 227: 87-99Google Scholar age-related macular degeneration16Ho A.C. Kleinman D.M. Lum F.C. et al.Baseline visual acuity at wet AMD diagnosis predicts long-term vision outcomes: an analysis of the IRIS Registry.Ophthalmic Surg Lasers Imaging Retina. 2020; 51: 633-639Google Scholar or diabetic retinopathy,17Wykoff C.C. Khurana R.N. Nguyen Q.D. et al.Risk of blindness among patients with diabetes and newly diagnosed diabetic retinopathy.Diabetes Care. 2021; 44: 748-756Google Scholar and ocular complications associated with immune checkpoint inhibitors.18Sun M.M. Kelly S.P. Mylavarapu A.L. et al.Ophthalmic immune-related adverse events following anti-CTLA-4 or PD-1 therapy recorded in the American Academy of Ophthalmology IRIS Registry.J Clin Oncol. 2020; 38 (e15124–e15124)Google Scholar A recent study from the IRIS Registry Analytic Center Consortium, “Endophthalmitis Rate in Immediate Sequential versus Delayed Sequential Bilateral Cataract Surgery within the IRIS Registry Data,” also highlights the strength of the IRIS Registry, in that an enormous dataset can be available for a rapid, timely analysis.7Lacy M. Kung T.-P.H. Owen J.P. et al.Endophthalmitis rate in immediately sequential versus delayed sequential bilateral cataract surgery within the Intelligent Research in Sight (IRIS) Registry data.Ophthalmology. 2021 Jul 13; S0161-6420 (00519-4) (Online ahead of print)https://doi.org/10.1016/j.ophtha.2021.07.008Google Scholar Lacy et al7Lacy M. Kung T.-P.H. Owen J.P. et al.Endophthalmitis rate in immediately sequential versus delayed sequential bilateral cataract surgery within the Intelligent Research in Sight (IRIS) Registry data.Ophthalmology. 2021 Jul 13; S0161-6420 (00519-4) (Online ahead of print)https://doi.org/10.1016/j.ophtha.2021.07.008Google Scholar analyzed the extensive cataract surgery data in the IRIS Registry to compare rates of postoperative endophthalmitis after immediate sequential bilateral cataract surgery versus delayed sequential bilateral cataract surgery. This was in response to the editorial in Ophthalmology that discussed COVID-19–related challenges in managing surgical patients in ophthalmology just a few months earlier that year.19Ahmed I.I.K. Hill W.E. Arshinoff S.A. Bilateral same-day cataract surgery: an idea whose time has come #COVID-19.Ophthalmology. 2021; 128: 13-14Google Scholar Endophthalmitis after cataract surgery is a rare event, and previous studies have relied on much smaller sample sizes, potentially too small to determine accurate endophthalmitis rates after bilateral cataract surgery. The size of the IRIS Registry allowed this study to include 3.5 times more patients undergoing immediate sequential bilateral cataract surgery than previous similar studies.8Herrinton L.J. Liu L. Alexeeff S. et al.Immediate sequential vs. delayed sequential bilateral cataract surgery: retrospective comparison of postoperative visual outcomes.Ophthalmology. 2017; 124: 1126-1135Google Scholar,20Arshinoff S.A. Bastianelli P.A. Incidence of postoperative endophthalmitis after immediate sequential bilateral cataract surgery.J Cataract Refract Surg. 2011; 37: 2105-2114Google Scholar Based on data from more than 5 million patients undergoing cataract surgery, the study found no statistically significant difference in the rates of postoperative endophthalmitis between the immediate sequential bilateral cataract surgery group and the group that underwent delayed sequential bilateral cataract surgery or unilateral cataract surgery. Despite these successes, several challenges continue to exist in using the IRIS Registry data. Although the data collected from the clinicians who report to the IRIS Registry are quite extensive, to ensure patient confidentiality, strict criteria were implemented to limit the data variables that are accessible to researchers. Although clinicians own their individual practice data, the AAO owns the de-identified, aggregated data after it is uploaded to the IRIS Registry.3Parke 2nd, D.W. Rich 3rd, W.L. Sommer A. Lum F. The American Academy of Ophthalmology’s IRIS® Registry (Intelligent Research in Sight clinical data): a look back and a look to the future.Ophthalmology. 2017; 124: 1572-1574Google Scholar Although the goal is for the Analytic Center Consortium to receive a comprehensive version of the aggregated data that can be used for multiple studies, many important variables such as detailed medication data and practice geographic information were not accessible in the initial IRIS Registry versions made available to the analytic centers (codenamed Rome 1 and Rome 2). This was because of the imposition of patient privacy protections that were even stricter than the safeguards established by the Health Insurance Portability and Accountability Act. This is in contrast to what has traditionally been available to researchers outside the Analytic Center Consortium through the foundation, subspecialty society funded grants, or industry-sponsored mechanisms mentioned above. For such projects, the AAO provides a dataset that is specific to the study question or even performs the analyses to ensure Health Insurance Portability and Accountability Act compliance, and these datasets often include data fields that are not part of the Rome 1 or 2 versions. Multiple studies have been published through this route, all based on specially selected datasets and analyses that were tailored to the specific research question.13Vanner E.A. Sun C.Q. McSoley M.J. et al.Tube Versus Trabeculectomy IRIS® Registry one-year composite outcome analysis with comparisons to the randomized controlled trial.Am J Ophthalmol. 2021; 227: 87-99Google Scholar,16Ho A.C. Kleinman D.M. Lum F.C. et al.Baseline visual acuity at wet AMD diagnosis predicts long-term vision outcomes: an analysis of the IRIS Registry.Ophthalmic Surg Lasers Imaging Retina. 2020; 51: 633-639Google Scholar, 17Wykoff C.C. Khurana R.N. Nguyen Q.D. et al.Risk of blindness among patients with diabetes and newly diagnosed diabetic retinopathy.Diabetes Care. 2021; 44: 748-756Google Scholar, 18Sun M.M. Kelly S.P. Mylavarapu A.L. et al.Ophthalmic immune-related adverse events following anti-CTLA-4 or PD-1 therapy recorded in the American Academy of Ophthalmology IRIS Registry.J Clin Oncol. 2020; 38 (e15124–e15124)Google Scholar,21Rao P. Kaiser R. Lum F. et al.Reoperation rates of patients undergoing primary noncomplex retinal detachment surgery in a cohort of the IRIS Registry.Am J Ophthalmol. 2020; 222: 69-75Google Scholar, 22Pershing S. Lum F. Hsu S. et al.Endophthalmitis after cataract surgery in the United States: a report from the Intelligent Research in Sight Registry, 2013–2017.Ophthalmology. 2020; 127: 151-158Google Scholar, 23Glasser D.B. Parikh R. Lum F. Williams G.A. Intravitreal anti-vascular endothelial growth factor cost savings achievable with increased bevacizumab reimbursement and use.Ophthalmology. 2020; 127: 1688-1692Google Scholar Significant strengths of the IRIS Registry data include not only the pure number of data points that allow observation of rare events, but also the potential to analyze clinical variables beyond the standard diagnosis and procedure codes. The recently updated version of de-identified IRIS Registry data, Chicago, contains many additional variables, such as medication, cup-to-disc ratio, and refraction data, compared with those provided in earlier versions. Additionally, it provides a single standardized resource for all analyses, including the Analytic Center Consortium and the other supported programs, which should decrease discrepancies in available data quality. As the number of important clinical variables become available, the IRIS Registry will allow more sophisticated analyses such as feature-based analyses, where researchers identify biomarkers of a disease or its progression or generate new avenues of investigation using a purely data-driven, hypothesis-agnostic approach.24Lee C.S. Brandt J.D. Lee A.Y. Big data and artificial intelligence in ophthalmology: where are we now?.Ophthalmology Science. 2021; 1: 100036Google Scholar In addition, findings from IRIS Registry studies that are consistent with other study results from smaller populations with limited geographic representation would support the validity of those findings in a national sample. However, the inherent limitations of a large, clinical practice-based dataset, including missing data and coding errors, must be considered at all times.25Lee C.S. Lee A.Y. Holland G.N. et al.Big data and uveitis.Ophthalmology. 2016; 123: 2273-2275Google Scholar Undoubtedly, the completeness of clinical notes depends on factors including clinicians’ documentation habits or examination settings within the IRIS Registry. Even in the updated version, the de-identified dataset still lacks important variables such as refractive target, axial length, and imaging results. Also, the dataset is ophthalmology centric, and therefore, the potential to investigate any correlations between ophthalmic findings and systemic diagnoses or medications is limited. Any free-written text in the electronic health record will remain unavailable for the foreseeable future. Future goals include automatic abstractions of free-written text and numeric data from diagnostic instruments such as visual fields and retinal imaging. Despite these limitations, immeasurable value exists in being able to assess the routine clinical practice patterns and clinical outcomes that often differ from the results of randomized clinical trials. Still, novel findings from big data may not be possible to validate because of the lack of other independent datasets of similar size or quality. Thus, researchers must be cautious in understanding the scope and limitations of the available dataset and must perform careful sensitivity analyses to explain the plausibility of any results that deviate from previous literature.26Thabane L. Mbuagbaw L. Zhang S. et al.A tutorial on sensitivity analyses in clinical trials: the what, why, when and how.BMC Med Res Methodol. 2013; 13: 92Google Scholar The IRIS Registry is an exceptional, evolving, and ever-expanding resource that will enable great progress in ophthalmology research. The long-term vision for the IRIS Registry, to become a multidimensional dataset that incorporates multimodal and nonophthalmic medical data, is truly exciting. As it currently stands, the IRIS Registry Analytic Center Consortium is uniquely positioned to address relevant research questions because their investigators were instrumental in developing the data abstraction and analysis methods, are aware of the limitations in the datasets available to them, and are capable of adjusting their analyses to accommodate these limitations. Additional centers have been accepted to join the IRIS Registry Analytic Center Consortium, and this process will continue on a regular basis. The experience gained by the 4 analytic centers from the early challenges will be instrumental in expediting the onboarding and success of new centers. Journal editors, reviewers, and the general readership should be aware of current strengths and limitations of the IRIS Registry Analytic Center Consortium projects. Further collaborations with additional centers and investigators and newer, more inclusive versions of the IRIS Registry dataset will enable the investigation of even more powerful study questions and will help to realize the potential and accomplish the scientific discovery goals of the IRIS Registry.

Utility of Removal of Vitreous Cortex Remnants during Vitrectomy for Primary Rhegmatogenous Retinal Detachment Repair

Abstract: Abstract Purpose To investigate the prevalence of vitreous cortex remnants (VCR) in primary rhegmatogenous retinal detachment (RRD) and the utility of VCR removal using diamond-dusted membrane scrapers (DDMS) during pars plana vitrectomy (PPV). Methods One hundred and eighty-seven eyes (187 consecutive patients) were retrospectively studied. We evaluated the prevalence of VCR on the retinal surface extending from the macula to outside the vascular arcade in eyes that underwent PPV for primary RRD by a single surgeon between July 2014 and February 2021. The VCR outside the vascular arcade was completely removed using a DDMS. Preoperative factors and surgical outcomes were compared between eyes with VCR removed intraoperatively to those without VCR. Results VCR was present and removed (group A) in 86 (46%) eyes and absent (group B) in 101 (54%) eyes. Patients with VCR were significantly older than those without (p = 0.006). The preoperative BCVA (logMAR) tended to be worse in group A (1.23 ± 0.92 [Snellen equivalent, 20/340]) than in group B (1.03 ± 0.89 [20/214]), however, the difference was not statistically significant (p = 0.095). There were no between-group differences in postoperative BCVA (group A; 0.44 ± 0.54 [20/55]; group B; 0.42 ± 0.50 [20/53]; p = 0.38). Single surgery anatomic success (group A; 90%, group B; 91%, p = 0.573) and the incidence of postoperative PVR (group A; 9%, group B; 6%, p = 0.554) were comparable between the groups. Conclusions Nearly half of the patients had VCR, which was more likely to occur in older patients. VCR removal resulted in favorable functional and anatomic outcomes similar to those in eyes without any VCR in patients with RRD.

Restoration of Cone Sensitivity to Individuals with Congenital Photoreceptor Blindness within the Phase 1/2 Sepofarsen Trial

Abstract: To understand consequences of reconstituting cone photoreceptor function in congenital binocular blindness resulting from mutations in the centrosomal protein 290 (CEP290) gene.Phase 1b/2 open-label, multicenter, multiple-dose, dose-escalation trial.A homogeneous subgroup of 5 participants with light perception (LP) vision at the time of enrollment (age range, 15-41 years) selected for detailed analyses. Medical histories of 4 participants were consistent with congenital binocular blindness, whereas 1 participant showed evidence of spatial vision in early life that was later lost.Participants received a single intravitreal injection of sepofarsen (160 or 320 μg) into the study eye.Full-field stimulus testing (FST), visual acuity (VA), and transient pupillary light reflex (TPLR) were measured at baseline and for 3 months after the injection.All 5 participants with LP vision demonstrated severely abnormal FST and TPLR findings. At baseline, FST threshold estimates were 0.81 and 1.0 log cd/m2 for control and study eyes, respectively. At 3 months, study eyes showed a large mean improvement of -1.75 log versus baseline (P < 0.001), whereas untreated control eyes were comparable with baseline. Blue minus red FST values were not different than 0 (P = 0.59), compatible with cone mediation of remnant vision. At baseline, TPLR response amplitude and latency estimates were 0.39 mm and 0.72 seconds, respectively, for control eyes, and 0.28 mm and 0.78 seconds, respectively, for study eyes. At 3 months, study eyes showed a mean improvement of 0.44 mm in amplitude and a mean acceleration of 0.29 seconds in latency versus baseline (P < 0.001), whereas control eyes showed no significant change versus baseline. Specialized tests performed in 1 participant confirmed and extended the standardized results from all 5 participants.By subjective and objective evidence, intravitreal sepofarsen provides improvement of light sensitivity for individuals with LP vision. However, translation of increased light sensitivity to improved spatial vision may occur preferentially in those with a history of visual experience during early neurodevelopment. Interventions for congenital lack of spatial vision in CEP290-associated Leber congenital amaurosis may lead to better results if performed before visual cortex maturity.

Factors affecting retinal redetachment after silicone oil removal for rhegmatogenous retinal detachments

Abstract: Preoperative macula and lens status, proliferative vitreoretinopathy, previous retinectomy, retinal detachment size, concomitant phacoemulsification, previous scleral buckling, and endolaser at the time of silicone oil removal surgery did not influence retinal redetachment rates. Longer silicone oil tamponade may be associated with higher reattachment rates but worse visual outcomes. Purpose: To report factors affecting the retinal redetachment rate after silicone oil removal (SOR) following rhegmatogenous retinal detachment (RRD) repair. Methods: Retrospective cohort study from December 1, 2014, to March 1, 2020, of 205 consecutive patients treated for RRD with silicone oil (SO) tamponade and subsequent SOR with at least 6-month follow-up. Primary outcome measure was the rate of retinal redetachment after SOR. Results: The retinal redetachment rate after SOR was 18.5%. Preoperative macula and lens status, proliferative vitreoretinopathy, previous retinectomy, retinal detachment size, concomitant phacoemulsification, previous scleral buckling, and endolaser during SOR did not affect the redetachment rate after SOR. Previous SO exchange was associated with increased redetachment (OR 2.53, 95% CI [1.11–5.80], P = 0.0278). Twelve months of SO tamponade had lower redetachment rates compared with 3 months (OR 0.25, 95% CI [0.04–0.09], P = 0.048). Shorter SO tamponade (3 vs. 12 months) had better final visual outcomes after SOR (0.80 ± 0.61 vs. 1.41 ± 0.66, P < 0.0001). Conclusion: No preoperative or intraoperative factors in this analysis influenced the risk of redetachment after SOR except duration of SO tamponade and previous SO exchange. Although longer SO tamponade duration may be associated with lower rates of redetachment, visual outcomes may be worse.

Stellate nonhereditary idiopathic foveomacular retinoschisis and an approach to the differential diagnosis of macular star

Abstract: Purpose of review This review aims to introduce stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) and its differential diagnosis. We summarize findings from case reports and series published in the last few years on the clinical and imaging findings in SNIFR. Recent findings SNIFR presents as either a unilateral or bilateral macular star on fundus examination without clinical or imaging evidence of exudation or frank vitreomacular traction. optical coherence tomography (OCT) imaging shows schisis cavities in the Henle fibre and outer plexiform layers that correspond to the stellate en face findings. Visual acuity is usually minimally affected, and the presence of significant vision loss should prompt high clinical suspicion for alternate diagnoses. Summary SNIFR is a recently characterized clinical entity that serves as an important addition to the differential diagnosis of a macular star. It is a diagnosis of exclusion and should be distinguished from other causes of macular star such as neuroretinitis, vitreomacular traction, ocular manifestations of malignant hypertension, congenital juvenile X-linked macular schisis, myopic maculopathy, optic pit maculopathy, nicotinic acid maculopathy or taxane maculopathy among others.

Factors Associated with Fluctuations in Central Subfield Thickness in Patients with Diabetic Macular Edema Using Diabetic Retinopathy Clinical Research Protocols T and V

Abstract: To identify baseline ocular and systemic factors associated with central subfield thickness (CST) fluctuations in patients with diabetic macular edema (DME) using data from Diabetic Retinopathy Clinical Research Protocols T and V.Post hoc analysis of clinical trial databases.Patients in Protocols T and V.The standard deviation (SD) of all recorded CSTs for each patient during each Protocol's study period was calculated. The CST SD (corresponding to CST fluctuations) for each patient was analyzed against baseline ocular and systemic factors using linear regression analyses. Each Protocol was analyzed separately.Factors associated with CST fluctuations.A total of 1197 eyes of 1197 subjects were included. In Protocol T (559 eyes, mean CST SD was 56.4 ± 35.1 microns), using multivariate linear regression analysis, baseline urine albumin/creatine ratio (for every 1000 mg/g, CST point estimate 3.50, 95% confidence interval [CI] 0.58 to 6.43, P = 0.0190), and baseline CST (for every 10 microns, 0.87, 95% CI 0.58 to 1.16, P < 0.0001) were positively associated with CST fluctuations. Baseline visual acuity (for every 10 ETDRS letters, -9.52, 95% CI -11.89 to -7.15, P < 0.0001) was negatively associated with CST fluctuations. In Protocol V (638 eyes, mean CST SD 36.6 ± 28.4 microns), gender (female, 2.18, 95% CI 0.30 to 4.06, P = 0.0227), baseline CST (for every 10 microns, 2.51, 95% CI 2.21 to 2.82, P < 0.0001), systolic blood pressure (for every 1 mm of mercury, 0.11, 95% CI 0.01 to 0.21, P = 0.0261), and observation with deferred anti-VEGF injections (5.04, 95% CI 2.51 to 7.58, P < 0.0001) were positively associated with CST fluctuations. Type 2 diabetes (-7.37, 95% CI -13.64 to -1.11, P = 0.0209) and prompt anti-VEGF injections (-6.51, 95% CI -9.07 to -3.96, P < 0.0001) were negatively associated with CST fluctuations.Worse visual acuity at baseline, baseline renal disease, hypertension, female gender, type 1 diabetes, and delayed anti-VEGF treatment may be associated with increased CST fluctuations in patients with DME. Addressing these parameters may limit CST fluctuations and help identify patients requiring more frequent monitoring or treatment.

Pilocarpine 1.25% and the changing landscape of presbyopia treatment

Abstract: Purpose of review Despite affecting approximately 1.8 billion individuals worldwide, until recently, a pharmacologic treatment for presbyopia was not available. This special commentary reviews the treatment of presbyopia with a focus on the recently approved medication Vuity (pilocarpine 1.25%, Allergan, an AbbVie Company). Recent Findings Vuity is a re-engineered formulation of pilocarpine 1.25% specifically designed for the treatment of presbyopia. Recently published results from the GEMINI 1 Phase 3 clinical trial reported improvement in distance corrected near vision without significant compromise in distance vision. No unexpected safety findings were reported with mild headache being the most common adverse event. Notably, there were no reported cases of retinal detachment or angle closure during the 30-day phase 3 clinical trials. Summary Vuity is the first treatment designed and FDA approved to treat the growing presbyopia market. Phase 3 clinical trials demonstrated its ability to improve near vision without significant compromise in distance vision. We recognize this paradigm shift in the treatment of presbyopia and anxiously await additional treatment options for this ubiquitous condition.

Prevalence, characteristics, and outcomes of rhegmatogenous retinal detachment in eyes with trabeculectomy or glaucoma drainage devices

Abstract: We report the outcomes of patients who developed rhegmatogenous retinal detachments after incisional glaucoma surgery. These eyes tended to present with more severe retinal detachments and had poor visual acuity outcomes. The 5-year prevalence of rhegmatogenous retinal detachments after glaucoma surgery was 0.71%. Purpose: To describe the prevalence, management, and outcomes of rhegmatogenous retinal detachment (RRD) after incisional glaucoma filtering surgery. Methods: All patients with a history of trabeculectomy or glaucoma drainage device surgery who were subsequently diagnosed with an RRD from January 1, 2016, to January 1, 2021, at the Wills Eye Hospital were identified. Results: Forty-six eyes met the inclusion criteria. The mean age was 60.7 ± 19.6 years, and 15 patients (32.6%) were female. Of all eyes, 34 (73.9%) were diagnosed with primary open-angle glaucoma. The mean time from most recent incisional glaucoma surgery to RRD diagnosis was 1,133 ± 1,644 days. There were 19 eyes (41.3%) with preoperative proliferative vitreoretinopathy (9 eyes [19.6%] with Grade C proliferative vitreoretinopathy) and 35 eyes (76.1%) had macula-off RRD at the time of presentation. At RRD presentation, 4 eyes (8.7%) had concomitant endophthalmitis, 5 (10.9%) had concurrent choroidal detachment, and 2 (4.7%) had concurrent vitreous hemorrhage. Primary vitrectomy was performed in most (91.3%) cases. Silicone oil tamponade was often required (71.1%). The single surgery success rate was 65.2% (30 of 46). The mean preoperative logarithm of the minimum angle of resolution visual acuity was 1.72 ± 0.78 (Snellen acuity 20/1,050), and the mean final postoperative logarithm of the minimum angle of resolution was 1.59 ± 0.89 (20/778, P = 0.2853). Of glaucoma surgeries performed, the 5-year prevalence of RRD was 0.71% (26 of 3,664, 95% Poisson confidence interval 0.48%–1.04%). Conclusion: The 5-year prevalence of RRDs after trabeculectomy or glaucoma drainage device was 0.71%. Most patients presented with macula-involving detachments, often with proliferative vitreoretinopathy. Anatomical and visual outcomes were poor.

Refractive error change during treatment of diabetic macular edema

Abstract: Supplemental Digital Content is Available in the Text. Patients with diabetic macular edema undergoing anti–vascular endothelial growth factor injections experience minimal changes in their refractor error. Therefore, proper correction and spectacle prescription should be considered for these patients regardless of degree of macular edema. Purpose: To evaluate the impact of anti–vascular endothelial growth factor therapy on the refractive error in eyes with diabetic macular edema. Methods: Post hoc analysis of Diabetic Retinopathy Clinical Research protocol T. Spherical equivalent (SE) was calculated for study and fellow eyes at baseline, 1-year, and 2-year visits. The SE change of the eyes with edema was compared with those with resolved edema. The correlation between refractive error changes and central subfield thickness was evaluated. Results: Among 543 study eyes, SE changed from −0.17 (2.04) D at baseline visit to −0.16 (2.14) D at 2 years giving a hyperopic shift of 0.04 (0.82) D (P = 0.022). Among fellow eyes, mean (SD) SE changed from −0.19 (2.1) D at baseline to −0.11 (2.1) D at 2 years, giving a hyperopic shift of 0.12 (0.84) D (P = 0.001). No significant difference in SE shift was found between eyes with and without edema at 2 years in phakic (0.12D and 0.08 D, P = 0.87) and pseudophakic eyes (−0.24D and −0.08D, P = 0.30). The SE shift was not correlated with central subfield thickness change at the end of the second year (r = 0.02, P = 0.62). Conclusion: Diabetic macular edema patients have minimal changes in refractive error. The correction of refractive error may be considered during treatment, regardless of the presence of edema.

Pilocarpine 1.25% and the changing landscape of presbyopia treatment.

Abstract: PURPOSE OF REVIEW Despite affecting approximately 1.8 billion individuals worldwide, until recently, a pharmacologic treatment for presbyopia was not available. This special commentary reviews the treatment of presbyopia with a focus on the recently approved medication Vuity (pilocarpine 1.25%, Allergan, an AbbVie Company). RECENT FINDINGS Vuity is a re-engineered formulation of pilocarpine 1.25% specifically designed for the treatment of presbyopia. Recently published results from the GEMINI 1 Phase 3 clinical trial reported improvement in distance corrected near vision without significant compromise in distance vision. No unexpected safety findings were reported with mild headache being the most common adverse event. Notably, there were no reported cases of retinal detachment or angle closure during the 30-day phase 3 clinical trials. SUMMARY Vuity is the first treatment designed and FDA approved to treat the growing presbyopia market. Phase 3 clinical trials demonstrated its ability to improve near vision without significant compromise in distance vision. We recognize this paradigm shift in the treatment of presbyopia and anxiously await additional treatment options for this ubiquitous condition.

Intravitreal Nesvacumab (Anti-Angiopoietin-2) Plus Aflibercept in Neovascular AMD: Phase 2 ONYX Randomized Trial

Abstract: Purpose: To compare intravitreal nesvacumab (anti-angiopoietin-2) + aflibercept vs intravitreal aflibercept injection (IAI) in neovascular age-related macular degeneration (nAMD). Methods: Eyes were randomized (1:2:3) to nesvacumab 3 mg + aflibercept 2 mg (LD combo), nesvacumab 6 mg + aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, week 4, and week 8. The LD combo was continued every 8 weeks (q8w). At week 12, the HD combo was re-randomized to q8w or every 12 weeks (q12w) and IAI was re-randomized to q8w, q12w, or HD combo q8w through week 32. Results: The study comprised 365 eyes. At week 12, the mean best-corrected visual acuity (BCVA) gains from baseline were similar in the LD combo group, HD combo group, and IAI group (5.2 letters, 5.6 letters, and 5.4 letters, respectively); the mean central subfield thickness (CST) reductions were similar (182.2 µm, 200.0 µm, and 178.6 µm, respectively). The mean changes in BCVA and CST through week 36 were similar across groups. At week 12, complete retinal fluid resolution was observed in 49.1% (LD combo), 50.8% (HD combo), and 43.6% (IAI) of eyes; the proportions with a CST of 300 μm or less were similar across groups. Numerical trends at week 32 toward complete retinal fluid resolution with combination treatment were not maintained at week 36. Serious ocular adverse events were infrequent and comparable across groups. Conclusions: In nAMD, nesvacumab + aflibercept showed no additional BCVA or CST benefit over IAI monotherapy.