Patterns of anti-vascular endothelial growth factor discontinuation in neovascular age-related macular degeneration.

OBJECTIVE: To report on anti-vascular endothelial growth factor (anti-VEGF) discontinuation in neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive nAMD patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Demographics, treatment start and end dates, number of injections, treatment length, reason for discontinuation, and baseline and final data (i.e., age, best-corrected visual acuity, and central subfield thickness) were recorded. Statistical analyses using STATA 17.0 assessed differences between baseline and final values and between treatment-discontinuation subgroups. RESULTS: A total of 619 eyes of 502 treatment-naive patients (9015 injections) were included (age, 81.6 ± 8.4 years; 64.0% female). Discontinuation rate was 58.3% (361 of 619), with 310 patients discontinuing because of the lack of visual benefit (n = 152), severe comorbidity or death (n = 82), transferred (n = 33), stable off active treatment (n = 19), lack of benefit plus stable off treatment (n = 14), patient decision (n = 6), and ocular comorbidity (n = 4). Among the 309 remaining patients, 51 (16.5%) were lost to follow-up. Discontinuation occurred within the first year in 49.3% (n = 178). Visual acuity was at least maintained in all groups and improved in the following groups: severe comorbidity or death (p < 0.0001), lost to follow-up (p = 0.0003), transferred (p = 0.0004), and stable off treatment (p = 0.0053). The lack of visual benefit group had no improvement in vision regardless of treatment length. Compared with other subgroups, those stable off treatment group was younger (p = 0.0055), had better baseline vision (p = 0.0018), received more injections (p = 0.0437) over a longer time (p = 0.0034), and achieved better final vision (p < 0.0001). CONCLUSION: While there was a high discontinuation rate over 7.5 years, most were attributable to disease or treatment factors and nonmodifiable patient factors. Discontinuation frequently occurred within the first year.

Treatment discontinuation patterns of anti VEGF in retinal vein occlusion.

OBJECTIVE: The purpose of this research is to report on real-world anti-vascular endothelial growth factor (anti-VEGF) treatment patterns in retinal vein occlusions (RVO). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive RVO patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Medical records available until June 2022 were reviewed. Demographics, diagnosis, number of injections, treatment length, reason for discontinuation, and baseline and final data (e.g., date, age, best-corrected visual acuity [BCVA], and central subfield thickness) were recorded. Statistical analyses performed with STATA 17.0 assessed differences between baseline and final values, branch (BRVO) and central retinal vein occlusion (CRVO), and treatment-discontinuation subgroups. RESULTS: A total of 219 treatment-naive eyes were included (70.3 ± 13.2 years of age, 52.5% female), with 99 BRVOs and 120 CRVOs (2482 injections). The discontinuation rate was 76.7% (168 of 219), with 72.7% of patients (77 of 99) with BRVOs and 75.8% of patients (91 of 120) with CRVOs discontinuing injections. Reasons for discontinuation included stable off active therapy (98 eyes), severe comorbidity or death (17 eyes), switched to intraocular steroid (implant or injection) (12 eyes), lack of visual benefit (10 eyes), ocular comorbidity (5 eyes), patient decision (5 eyes), and patient transfer (5 eyes). Among the remaining 67 eyes, 16 (24%) were lost to follow-up. Reasons for discontinuation differed between BRVO and CRVO patients (p = 0.002). Eyes with CRVO presented with worse BCVA (p < 0.0001) and achieved worse final BCVA (p < 0.0001), but both groups experienced improvements (p < 0.0001). Younger age, better baseline BCVA, and a diagnosis of BRVO were independent predictors of better final visual acuity. CONCLUSION: Over 7.5 years, treatment was discontinued for three-quarters of RVOs. Stable disease was the most common reason for discontinuation, with nearly half (45%) of all RVOs in the cohort stable off active therapy. Better visual outcomes were achieved in BRVO than in CRVO, although both groups benefited from treatment.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY MORPHOLOGY AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR: ALIGN Post Hoc Analysis.

PURPOSE: To compare foveal avascular zone (FAZ) geometric indices using optical coherence tomography angiography (OCTA) in pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). FAZ morphology was assessed as a possible imaging feature of retinal displacement. METHODS: This ALIGN post hoc analysis included primary fovea-off RRDs that underwent successful PnR or PPV, and performed OCTA, and fundus autofluorescence at (FAF) 3 months postoperatively at St. Michael's Hospital, Toronto, Canada. FAZ area (mm 2 ), axial ratio, circularity, and roundness were measured, and FAF images were assessed for retinal displacement. RESULTS: Seventy-two patients were included, 78% (56/72) were male mean age was 60 ± 9 years, and 60% (43/72) were phakic. Sixty-five percent (47/72) and 35% (25/72) underwent PnR and PPV, respectively. The mean baseline logarithm of the minimum angle of resolution visual acuity was 1.49 ± 0.76. FAZ circularity was lower after PPV (0.629 ± 0.120) versus PnR (0.703 ± 0.122); P = 0.016. Sixty-six patients had gradable FAF images. Retinal displacement was present in 29% (19/66), 84.2% (16/19) of which had displacement in the macula. FAZ circularity was lower in eyes with displacement in the macula (0.613 ± 0.110) versus those without displacement (0.700 ± 0.124); P = 0.015. There was a moderate negative correlation between 12-month aniseikonia and FAZ circularity(r = -0.262; P = 0.041). CONCLUSION: FAZ circularity was lower after PPV and in eyes with retinal displacement in the macula. Circularity was negatively correlated with 12-month aniseikonia scores. FAZ circularity may be another imaging feature to consider postoperatively after RRD repair.

A Novel Method of Quantifying Retinal Displacement Using Ultra-Widefield Fundus Autofluorescence Imaging.

PURPOSE: To introduce a novel method of quantifying retinal displacement in three dimensions (3D) using ultra-widefield fundus autofluorescence (UWF-FAF). DESIGN: Prospective clinical cohort study. METHODS: Patients with primary macula-off rhegmatogenous retinal detachment (RRD) treated with pneumatic retinopexy (PnR) or vitrectomy were included. Masked graders selected corresponding points on retinal vasculature and retinal vessel printings (RVPs) within Zone 1, a circular region centered on the fovea with a radius extending to the optic disc (OD) center. Two-dimensional (2D) UWF-FAF was projected to 3D using OD and foveal coordinates. Vertical, horizontal, and diagonal distances between corresponding vessel and RVPs were calculated. Vector displacement of the RVPs to vessels were averaged. RESULTS: A total of 170 retinal vessel-RVP pairs were identified from 54 UWF-FAF images. Mean displacement in Zone 1 was 0.36 ± 0.38 mm, with an absolute mean angle of displacement of 94.93 ± 41.48° and directionality of 191.84 ± 97.39°. Mean Zone 1 displacement was 0.44 ± 0.42mm and 0.21 ± 0.27 mm in vitrectomy (n = 35) and PnR (n = 19) eyes, respectively (P = .041), with no differences in mean angle of displacement/directionality. CONCLUSIONS: A novel method of quantifying the magnitude and direction of retinal displacement is presented, accounting for the spherical 3D curvature of the eye by using corresponding points on retinal vessels and RVPs using UWF-FAF. This provides a 3D vector of displacement agnostic of a singular fixation point such as the optic disc. Accurately quantifying the magnitude and angle/direction of displacement may allow for a better understanding of the mechanisms involved in retinal displacement in various surgical techniques, and a better assessment of the association with functional outcomes.

Paracentral acute middle maculopathy following hepatitis B vaccine.

PURPOSE: To report a case of paracentral acute middle maculopathy (PAMM) following Hepatitis B vaccine in a child. OBSERVATIONS: A 12-year-old healthy female presented with a paracentral scotoma in the right eye due to PAMM, likely associated with a recent Hepatitis B vaccine. CONCLUSIONS: Despite the great importance of vaccines, it is critical to promptly recognize their rare ocular complications, such as the vaccine associated PAMM described in this report.

Perfluorocarbon liquid assisted drainage and tamponade associated retinal displacement: A unifying theory on the etiology of retinal folds, slippage and retinal displacement.

PURPOSE: To determine the integrity of re-attachment in a macula-off detachment repaired with pars plana vitrectomy using perfluorocarbon liquid (PFO) assisted drainage and short-term tamponade with no air-fluid exchange and to discuss a unifying theory on the etiology of retinal malappositions including retinal displacement (stretch), retinal slippage and full-thickness macular folds. OBSERVATIONS: Significant retinal displacement was observed on fundus autofluorescence imaging following retinal detachment repair using PFO, along with significant metamorphopsia and aniseikonia. The retinal displacement was in the exact direction as the flow of subretinal fluid during the PFO assisted drainage. CONCLUSIONS AND IMPORTANCE: Routine use of PFO to assist with drainage and leaving it in as a short-term tamponade for uncomplicated retinal detachment repair may result in inadvertent retinal displacement as a result of the forced flow of subretinal fluid leading to a stretch of the retina. This case supports a unifying theory on the etiology of retinal malappositions including retinal displacement (stretch), retinal slippage and full thickness macular fold. Retinal malappositions occur because of the flow of subretinal fluid either a) induced by the buoyant force of the tamponade and gravity in a direction related to post-operative head position (often towards inferior periphery) in the case of retinal displacement (stretch) or b) from anterior to posterior during air-fluid exchange in the case of full-thickness macular fold with posterior redundancy and anterior stretch or slippage.

MINIMAL GAS VITRECTOMY TECHNIQUE FOR REDUCING RISK OF RETINAL DISPLACEMENT FOLLOWING RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To present a novel technique, minimal gas vitrectomy, as a means of potentially minimizing retinal displacement compared with standard vitrectomy for select cases. METHODS: A patient with a macula off retinal detachment and break at 12 o'clock underwent a 23-gauge pars plana vitrectomy, endodiathermy of the superior break in detached retina and endolaser of the inferior break in attached retina, without air-fluid exchange. Suturing of sclerotomies, anterior chamber paracentesis of 0.3 mL followed by intravitreal injection of 0.6 mL pure SF 6 was then performed. Positioning was face down for 6 hours and then steamroll up with laser retinopexy to the superior break the following day. RESULTS: Postoperative fundus autofluorescence imaging demonstrated no retinal displacement. CONCLUSION: The minimal gas vitrectomy technique has the potential to minimize retinal displacement by using a smaller gas tamponade compared to standard vitrectomy in certain cases with specific postoperative positioning instructions.

Understanding the mechanism of retinal displacement following rhegmatogenous retinal detachment repair: A computer simulation model.

PURPOSE: Retinal displacement is common following rhegmatogenous retinal detachment (RRD) repair. A computer simulation was developed to assess forces applied by a gas tamponade of various sizes in the setting of pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV). DESIGN: Computer simulation model. METHODS: The contact angle and pressure between the tamponade and the retina were calculated using interfacial tension and the densities of gas and vitreous. A simulation determined the dynamics of fluid motion in the subretinal space and calculated deformations of the retina. RESULTS: Bulk flow of fluid away from the tamponade in a direction along gravity stretched the retina and caused displacement in the simulations. Extent of displacement is attributable to the subretinal fluid layer thickness, and area of contact and contact pressure applied by the tamponade. Larger gas tamponades have greater contact pressure applied to the retina. Reducing gas bubble size from 93% to 6.25% with PPV versus PnR, there was a 79% reduction in the mean contact pressure (1.4 mmHg-0.29 mmHg), and a 93% reduction in the surface area of contact (11 cm2 -0.8 cm2 ). Therefore, the contact force applied to the entire retina decreases by 97% from 83 mN (PPV) to 2.9 mN (PnR). The model resembling PnR had more than three times less displacement compared to PPV. CONCLUSIONS: This model provides a framework to study retinal displacement. Our findings suggest that proportional to their size, gas tamponades stretched the retina by displacing subretinal fluid following RRD repair.

Postoperative Photoreceptor Integrity Following Pneumatic Retinopexy vs Pars Plana Vitrectomy for Retinal Detachment Repair: A Post Hoc Optical Coherence Tomography Analysis From the Pneumatic Retinopexy Versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial.

IMPORTANCE: Pneumatic retinopexy (PnR) is associated with superior visual acuity and reduced vertical metamorphopsia compared with pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD). It is important to determine postoperative photoreceptor integrity with both surgical techniques. OBJECTIVE: To compare photoreceptor integrity on spectral domain-optical coherence tomography (SD-OCT) between PnR and PPV at 12 months postoperatively. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of the Pneumatic Retinopexy Versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) conducted between August 2012 and May 2017 at St Michael's Hospital, Toronto, Ontario, Canada. Primary RRDs with specific criteria were included. Data were analyzed between April and August 2020. INTERVENTION: Randomization to PnR vs PPV stratified by macular status. MAIN OUTCOMES AND MEASURES: Difference in proportion of patients with discontinuity of the ellipsoid zone (EZ) and external limiting membrane (ELM) between groups assessed independently by 2 masked graders at an external masked image reading center. RESULTS: A total of 150 participants completed the 12-month follow-up visit. A total of 145 patients (72 PPV and 73 PnR) had gradable spectral-domain optical coherence tomography at 12 months. Analysis of the central 3-mm (foveal) scans found that 24% (n = 17 of 72) vs 7% (n = 5 of 73) displayed EZ discontinuity (difference, 17%; odds ratio [OR], 4.204; 95% CI, 1.458-12.116; P = .005) and 20% (n = 14 of 71) vs 6% (n = 4 of 73) displayed ELM discontinuity (difference, 14%; OR, 4.237; 95% CI, 1.321-13.587; P = .01) in the PPV and PnR groups, respectively. Analysis of the 6-mm (foveal and nonfoveal) scans revealed that EZ and ELM discontinuity was greater in the PPV vs PnR groups (EZ, 32% [n = 23 of 72] vs 11% [n = 8 of 73]; difference, 21%; OR, 3.814; 95% CI, 1.573-9.249; P = .002; ELM, 32% [n = 23 of 71] vs 18% [n = 13 of 73]; difference, 14%; OR, 2.211; 95% CI, 1.015-4.819; P = .04). CONCLUSIONS AND RELEVANCE: Discontinuity of the EZ and ELM was more common at 12 months postoperatively following PPV vs PnR for RRD repair. The findings of this post hoc analysis suggest that less discontinuity of the EZ and ELM may provide an anatomic basis for the previously reported superior functional outcomes with PnR, although the analysis does not prove a cause-and-effect relationship. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01639209.

Pneumatic Retinopexy in Patients with Primary Rhegmatogenous Retinal Detachment Meeting PIVOT Trial Criteria.

PURPOSE: To identify the proportion of patients with primary rhegmatogenous retinal detachment (RRD) presenting to a retina practice that meet 'Pneumatic Retinopexy versus Vitrectomy for the Management of Primary RRD' (PIVOT) trial criteria and to assess anatomic and functional outcomes of pneumatic retinopexy (PnR) in this population. DESIGN: Retrospective consecutive case series. PARTICIPANTS: Patients with primary RRD treated between October 2009 and November 2017 at an academic vitreoretinal practice in Canada. METHODS: Medical records of all cases >18 years old with primary RRD were reviewed and the proportion of patients meeting PIVOT criteria was determined. Patients that met PIVOT criteria who underwent PnR with a follow-up >3 months were included for further analysis. MAIN OUTCOME MEASURES: The primary outcome was the primary retinal reattachment rate at 12 months among patients meeting PIVOT criteria undergoing PnR. RESULTS: A total of 1,091 patients were identified, of which 577 (52.9%) met PIVOT criteria. Of these, 482/577 (83.5%) underwent PnR, but 54/482 (11.2%) were excluded as these had been enrolled in the PIVOT trial, and another 40/482 (8.3%) were excluded due to short follow-up (<3 months). Therefore, data pertaining to 388 patients is included in our analysis. 79.4% (308/388), 78.2% (280/358), 76.5% (241/315) and 73.9% (178/241) of patients who followed up at 3, 6, 12, and 24 months, respectively, had primary anatomic reattachment. A total of 20.6% (80/388) of patients did not reattach with the initial PnR or re-detached in the early post-procedure period (3 months), 2.1% (8/388) of patients re-detached between 3-12 months, and 1.3% (5/388) re-detached after 1 year. Phakic lens status was the only significant predictor of PnR success at 12 months in a multivariate logistic regression analysis (P = 0.006). Mean logMAR VA improved from 0.90 ± 0.90 (Snellen 20/159) at baseline t 0.34 ± 0.40 (Snellen 20/44) at 12 months (P < 0.001). CONCLUSIONS: Over 50% of patients presenting to an academic tertiary retina practice with primary RRD met PIVOT criteria and were eligible for PnR. Evidence from this study demonstrates a durable primary anatomic retinal reattachment rate with PnR in patients fulfilling PIVOT criteria, with similar results to those encountered in the PIVOT trial.

Changes in Aqueous Cytokine Levels Following Intravitreal Aflibercept in Treatment-Naive Patients with Diabetic Macular Edema.

Purpose: To investigate the changes in aqueous humor cytokine levels in response to short-term aflibercept therapy in treatment-naive patients with center-involving diabetic macular edema (DME). Methods: This is a prospective cohort study that included patients with treatment-naive DME with central subfield macular thickness ≥310 µm on optical coherence tomography from July 2015 to May 2017. Patients received 3 monthly intravitreal aflibercept injections. Aqueous samples for cytokine analysis were obtained before the first and third injections. Levels of various cytokines were measured using multiplex immunoassay. Main outcome measures were changes in aqueous cytokine levels from baseline to month 2. Results: A total of 17 patients were enrolled and 16 completed the study. The mean age was 57.2 ± 8.1 years. The following cytokines were significantly higher at month 2 versus baseline: transforming growth factor-beta (TGF-ß)1 (P = 0.004), TGF-ß2 (P = 0.017), inducible protein (IP)-10 (P = 0.011), and hepatocyte growth factor (HGF) (P = 0.02). There were significant reductions in the levels of vascular endothelial growth factor (VEGF) (P < 0.001), placental growth factor (PlGF) (P = 0.028), interleukin (IL)-6 (P = 0.011), and platelet-derived growth factor-AA (PDGF-AA) (P = 0.003). Conclusions: In treatment-naive patients with DME, short-term aflibercept therapy not only results in VEGF and PlGF suppression, but also leads to reduced levels of IL-6 and PDGF-AA and higher concentrations of TGF-ß1, TGF-ß2, HGF, and IP-10.

Retinal Displacement Following Pneumatic Retinopexy vs Pars Plana Vitrectomy for Rhegmatogenous Retinal Detachment.

Importance: Retinal displacement following rhegmatogenous retinal detachment repair may have consequences for visual function. It is important to know whether surgical technique is associated with risk of displacement. Objective: To compare retinal displacement following rhegmatogenous retinal detachment repair with pneumatic retinopexy (PR) vs pars plana vitrectomy (PPV). Interventions or Exposures: Fundus autofluorescence images were assessed by graders masked to surgical technique. Design, Setting, and Participants: A multicenter retrospective consecutive case series in Canada and the UK. A total of 238 patients (238 eyes) with rhegmatogenous retinal detachments treated with PR or PPV who underwent fundus autofluorescence imaging from November 11, 2017, to March 22, 2019, were included. Main Outcomes and Measures: Proportion of patients with retinal displacement detected by retinal vessel printings on fundus autofluorescence imaging in PR vs PPV. Results: Of the 238 patients included in the study, 144 were men (60.5%) and 94 were women (39.5%); mean (SD) age was 62.0 (11.0) years. Of the 238 eyes included in this study, 114 underwent PR (47.9%) and 124 underwent PPV (52.1%) as the final procedure to achieve reattachment. Median time from surgical procedure to fundus autofluorescence imaging was 3 months (interquartile range, 1-5 months). Baseline characteristics in both groups were similar. The proportion of eyes with retinal vessel printing on fundus autofluorescence was 7.0% for PR (8 of 114) and 44.4% for PPV (55 of 124) (37.4% difference; 95% CI, 27.4%-47.3%; P < .001). Analysis based on the initial procedure found that 42.4% (42 of 99) of the eyes in the PPV group vs 15.1% (21 of 139) of the eyes in the PR group (including 13 PR failures with subsequent PPV) had displacement (27.3% difference; 95% CI, 15.9%-38.7%; P < .001). Among eyes with displacement in the macula, the mean (SD) displacement was 0.137 (0.086) mm (n = 6) for PR vs 0.297 (0.283) mm (n = 52) for PPV (0.160-mm difference; 95% CI, 0.057-0.263 mm; P = .006). Mean postoperative logMAR visual acuity was 0.31 (0.32) (n = 134) (Snellen equivalent 20/40) in eyes that initially underwent PR and 0.56 (0.42) (n = 84) (Snellen equivalent 20/72) in eyes that had PPV (-0.25 difference; 95% CI, -0.14 to -0.35; P < .001). Among eyes with displacement, mean postoperative logMAR visual acuity was 0.42 (0.42) (n = 20) (Snellen equivalent 20/52) in those that initially underwent PR and 0.66 (0.47) (n = 33) (Snellen equivalent 20/91) in those that initially underwent PPV (-0.24 difference; 95% CI, -0.48 to 0.01; P = .07). Conclusions and Relevance: These findings suggest that retinal displacement occurs more frequently and is more severe with PPV vs PR when considering the initial and final procedure used to achieve retinal reattachment. Recognizing the importance of anatomic integrity by assessing retinal displacement following reattachment may lead to refinements in vitreoretinal surgery techniques.