International Classification System for Ocular Complications of Anti-VEGF Agents in Clinical Trials.

PURPOSE: Complications associated with intravitreal anti-VEGF therapies are reported inconsistently in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process. DESIGN: Systematic review and Delphi consensus process. PARTICIPANTS: Twenty-five international retinal specialists participated in the Delphi consensus survey. METHODS: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists who voted on inclusion, exclusion, rephrasing, and addition of complications. Furthermore, surveys determined specifiers for the selected complications. This iterative process helped to refine the final classification system. MAIN OUTCOME MEASURES: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration. RESULTS: After screening 18 229 articles, 130 complications were categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 complications (70%) after 3 rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 complications (52%) in the final list. A total of 14 complications (11%) met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds also were excluded from the final classification system after the Delphi process terminated. In addition, 47 of 75 proposed complication specifiers (63%) were included based on participant agreement. CONCLUSIONS: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Pedicle transposition flap, inverted flap, free flap, and standard peel for large full thickness macular holes: a comparative study.

PURPOSE: To compare anatomical and functional outcomes of four different techniques for the treatment of large idiopathic full-thickness macular holes (FTMH). METHODS: Single-centre retrospective study including 129 eyes of 126 patients with large (>500µm) FTMH between January 2018-October 2022. All patients underwent 23/25G vitrectomy and gas with standard internal limiting membrane (ILM) peel, pedicle transposition, inverted, or free flap technique. Postoperative OCT images were assessed by 2 independent masked graders. RESULTS: Mean age was 73.2 years (SD 8.4) with median F/U of 5 months (IQR 8). Overall anatomical success rate was 81%; significantly lower (59%) for the standard ILM peel (p<0.0001). The pedicle transposition flap showed superior visual recovery compared to the free flap (+27 vs +12 ETDRS letters, p=0.02). At 3 months, restoration of the ELM was significantly better for the pedicle transposition flap compared to free flap and standard ILM peel (p=0.008 and p=0.03), and superior to all the other techniques at 6 months (p=0.02, p=0.04 and p=0.006). CONCLUSIONS: Standard ILM peel alone offers inferior outcomes for the management of large FTMH. Of the alternative ILM techniques, despite similar closure rates, foveal microstructural recovery is most complete following the pedicle transposition flap, and least complete following the free flap.

A randomised controlled trial evaluating internal limiting membrane peeling forceps in macular hole surgery.

PURPOSE: To assess study design and a range of anatomical and functional changes after internal limiting membrane (ILM) peeling using forceps developed for atraumatic ILM pick-up compared to standard forceps. METHODS: We conducted a masked proof-of concept randomised controlled trial (RCT) on 65 patients who underwent ILM peeling for idiopathic full-thickness macular hole (FTMH) using etched-tip forceps (etched-tip group, 33 eyes) compared to standard ILM forceps (smooth-tip group, 32 eyes). Patients were assessed preoperatively, 3 weeks, 3 and 6 months postoperatively. RESULTS: The primary closure rate was 95.4%. There was no statistically significant difference between the groups in terms of final visual acuity (66.9 vs 70.9 ETDRS letters, p = 0.13), difference of visual field mean deviation (1.32 vs 1.14 decibels), and number of eyes with pick-up-related retinal haemorrhages (16% vs 16%, p = 0.96), swelling of arcuate nerve fibre layer lesions (63% vs 55%, p = 0.54), number of dissociated optic nerve fibre layer lesions (31.4 vs 41.0, p = 0.16), nor inner retina defects (37% vs 22%, p = 0.17). Similar changes in inner retinal volumes were detected in all 9 sectors of an ETDRS grid except for a trend (p = 0.06) towards a lower reduction in the inferior inner sector in the etched-tip group. CONCLUSIONS: The study was successfully completed with masking maintained and a low risk of bias. Multiple endpoints relating to ILM peeling were assessed, and estimates were provided that can be used for future studies. Although the study was not powered to assess any specific endpoint, the anatomical and functional outcomes assessed did not significantly differ.

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.

SEQUENTIAL PNEUMATIC RETINOPEXIES FOR THE TREATMENT OF PRIMARY INFERIOR RHEGMATOGENOUS RETINAL DETACHMENTS WITH INFERIOR BREAKS: The Double-Bubble Approach.

PURPOSE: To evaluate a new approach of sequential pneumatic retinopexies for the management of inferior rhegmatogenous retinal detachments (RD) with inferior breaks. METHODS: Multicenter retrospective consecutive case series of inferior RDs caused by retinal breaks located within the inferior 4 clock hours treated with sequential pneumatic retinopexies, 24 to 48 hours apart. A total of 26 patients with inferior RDs secondary to one or more breaks between the 4 o'clock and 8 o'clock meridians were included from September 2007 to February 2012. RESULTS: The mean follow-up duration was 35.3 weeks. Anatomical success at 8 weeks was achieved in 65.4% of all patients (including those with giant retinal tear and patients with previous RD in the study eye). When excluding patients with giant retinal tear and previous RD in the study eye, the anatomical success rate increased to 70%. Overall, the mean visual acuity improved from 1.00 logMAR (Snellen equivalent 20/200) at baseline to 0.38 logMAR (Snellen equivalent 20/50) at last follow-up. CONCLUSION: Sequential pneumatic retinopexy offers a new viable surgical option for the treatment of RDs secondary to inferior breaks.

The Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT).

PURPOSE: The optimal surgery to repair rhegmatogenous retinal detachment (RRD) is unknown. The purpose of this trial was to compare outcomes of pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for the management of primary RRD. DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: Patients with RRD demonstrating a single retinal break or a group of breaks in detached retina within 1 clock hour above the 8- and 4-o'clock meridians, with any number, location and size of retinal breaks or lattice degeneration in attached retina. METHODS: Patients were randomized to undergo either PnR or PPV. Macula-on and macula-off patients were assigned to intervention group by stratified randomization and were treated within 24 and 72 hours, respectively. MAIN OUTCOME MEASURES: The primary outcome was 1-year Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA). Important secondary outcomes were subjective visual function (25-item National Eye Institute Visual Function Questionnaire), metamorphopsia score (M-CHARTS), and primary anatomic success. RESULTS: One hundred seventy-six patients were recruited between August 2012 and May 2016. ETDRS VA after PnR exceeded that after PPV by 4.9 letters at 12 months (79.9±10.4 letters vs. 75.0±15.2 letters; P = 0.024). Mean ETDRS VA also was superior for the PnR group compared with the PPV group at 3 months (78.4±12.3 letters vs. 68.5±17.8 letters) and 6 months (79.2±11.1 letters vs. 68.6±17.2 letters). Composite 25-item National Eye Institute Visual Function Questionnaire scores were superior for PnR at 3 and 6 months. Vertical metamorphopsia scores were superior for the PnR group compared with the PPV group at 12 months (0.14±0.29 vs. 0.28±0.42; P = 0.026). Primary anatomic success at 12 months was achieved by 80.8% of patients undergoing PnR versus 93.2% undergoing PPV (P = 0.045), with 98.7% and 98.6%, respectively, achieving secondary anatomic success. Sixty-five percent of phakic patients in the PPV arm underwent cataract surgery in the study eye before 12 months versus 16% in the PnR group (P < 0.001). CONCLUSIONS: Pneumatic retinopexy should be considered the first line treatment for RRD in patients fulfilling Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) recruitment criteria. Pneumatic retinopexy offers superior VA, less vertical metamorphopsia, and reduced morbidity when compared with PPV.

AQUEOUS HUMOR CYTOKINE LEVELS AS BIOMARKERS OF DISEASE SEVERITY IN DIABETIC MACULAR EDEMA.

PURPOSE: To determine whether aqueous cytokine levels correlate with disease severity in diabetic macular edema. METHODS: A prospective cross-sectional study of 49 adults with diabetes mellitus, centre-involving diabetic macular edema and central subfield macular thickness ≥310 µm on spectral domain optical coherence tomography. Clinical examination and aqueous sampling were carried out before an initial injection of ranibizumab. Multiplex immunoassay of sample was carried out for vascular endothelial growth factor, placental growth factor, transforming growth factor beta, intercellular adhesion molecule-1, interleukin (IL)-2, IL-3, IL-6, IL-8, IL-10, IL-17, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and epidermal growth factor. Multivariate robust regression models were constructed, and adjusted for age, lens status, or severity of retinopathy, and size of foveal avascular zone. RESULTS: Spectral domain optical coherence tomography macular volume was an excellent measure of disease severity, correlating strongly with central subfield macular thickness (P < 0.001), best-corrected Snellen visual acuity (P < 0.001), and baseline diabetic retinopathy severity (P = 0.01). Elevated aqueous intercellular adhesion molecule-1 correlated with greater macular volume (P = 0.002). No aqueous cytokine, including VEGF, correlated with central subfield macular thickness. There was an association between IL-10 levels and best-corrected Snellen visual acuity (P = 0.03). CONCLUSION: Aqueous intercellular adhesion molecule-1 correlates with disease severity as measured by macular volume on spectral domain optical coherence tomography, and IL-10 is associated with BCVA. Intercellular adhesion molecule-1 may be a clinically useful biomarker for diabetic macular edema severity.

The Royal College of Paediatrics and Child Health Retinopathy of Prematurity Screening Guidelines (2022): a series of treated infants falling outside the updated criteria.

BACKGROUND/OBJECTIVES: Screening for retinopathy of prematurity (ROP) is a core healthcare intervention in premature babies to avoid preventable sight loss. A variety of screening criteria are in place globally for this purpose. The Royal College of Paediatrics and Child Health recently updated the United Kingdom ROP screening guidelines (March 2022). A key change was the reduction in the gestational age (GA) to warrant retinal screening (from 32 to 31 weeks). SUBJECTS/METHODS: In the course of informal national surveillance during guideline development (2017-2022) and soon after, babies under our care falling outside the updated screening criteria who underwent treatment for ROP were identified. A retrospective case review was carried out. RESULTS: Six babies were identified as having undergone screening and treatment, prior to implementation of the new guidance. Screening and treatment would have been forfeited as per the March 2022 guidelines. All six had numerous systemic risk factors for developing ROP. Specifically, all had documented poor postnatal weight gain. CONCLUSIONS: We present this case series to bring forth an urgent discussion amongst key stakeholders as to whether the new guidance, as it stands, is safe and fit for purpose.

Platelet-rich plasma and macular hole surgery: A clue to their mode of action and the influence of anti-platelet agents.

PURPOSE: To present a case of refractory full-thickness macular hole (FTMH), in which autologous platelet-rich plasma (aPRP) was used on two consecutive occasions, and associated with successful closure only after complete cessation of anti-platelet therapy. METHODS: Interventional case report. RESULTS: A 63-year-old male with Alport syndrome underwent pars plana vitrectomy with internal limiting membrane peeling and gas for a large FTMH. The patient was on systemic anti-platelet agents for coronary disease. Post-operatively, the FTMH remained open and repeated surgery, augmented with aPRP, was performed. Although a thick pre-retinal coagulum was evident on optical coherence tomography on day one post-surgery, the second surgery failed. Ultimately, successful aPRP-augmented surgical closure of the FTMH was achieved only after complete cessation of systemic anti-platelet agents. CONCLUSION: Appropriate management of anti-platelet therapy may be relevant when planning aPRP use, though further large-scale studies are needed to assess the precise effect of anti-platelet therapy on the efficacy of aPRP, and to confirm the potential role of aPRP in patients with Alport syndrome.

Novel classification system for management of rhegmatogenous retinal detachment with minimally invasive detachment surgery: a network meta-analysis of randomized trials focused on patient-centred outcomes.

OBJECTIVE: To describe a novel classification system for primary rhegmatogenous retinal detachment (RRD) based on level 1 evidence assessing the functional outcomes of repair techniques with the goal of using a minimally invasive detachment surgery. METHODS: A systematic review and network meta-analysis of randomized, controlled trials comparing pneumatic retinopexy (PnR), scleral buckle (SB), or pars plana vitrectomy (PPV) for RRD was conducted. Primary outcomes were best-corrected visual acuity (BCVA), metamorphopsia, and operative complications. A meta-analysis was performed with a random effects maximum likelihood model, with outcomes of standardized mean difference (SMD) or risk ratio (RR) and 95% confidence interval. Inclusion and exclusion criteria were assessed to inform a classification system. RESULTS: Fourteen trials were included. RRDs were classified from categories 1-3 based on configuration (simple to complex). There was no significant difference in final BCVA between PnR and PPV (categories 1 and 2; SMD = -0.10, 95% CI -0.24 to 0.04), nor was a final BVCA difference found between SB and PPV (SMD = 0.01, 95% CI -0.05 to 0.08), combined SB + PPV and PPV (SMD = 0.02, 95% CI -0.08 to 0.12), or combined SB + PPV and SB (SMD = 0.01, 95% CI -0.11 to 0.12). SB had an elevated risk of choroidal detachment (RR = 5.17, 95% CI 1.68-15.97), hypotony (RR = 12.26, 95% CI 1.63-92.04), and strabismus or diplopia (RR = 5.86, 95% CI 1.04-32.91) compared with PPV but a lower risk of iatrogenic breaks (RR = 0.08, 95% CI 0.02-0.43). Vertical metamorphopsia scores were superior for PnR over PPV at 12 months (Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial, p = 0.026). CONCLUSION: This novel classification system may be useful for future trials assessing morphologic categories of RRD in a systematic manner. Minimally invasive detachment surgery may allow for trials to focus on maximizing functional outcomes while minimizing morbidity.

En Face OCT in Diagnosis of Persistent Subretinal Fluid and Outer Retinal Folds after Rhegmatogenous Retinal Detachment Repair.

PURPOSE: To evaluate the role of en face OCT as a diagnostic tool for the detection of persistent subretinal fluid (PSRF) and outer retinal folds (ORFs) after successful rhegmatogenous retinal detachment (RRD) repair. DESIGN: Observational post hoc analysis of 2 prospective surgical trials. PARTICIPANTS: All patients with gradable (signal strength ≥ 5 and no segmentation error) 6 × 6-mm2 macular cube scans obtained using spectral-domain OCT (Carl Zeiss Meditec) between 1 and 2 months after surgery were included in this study. METHODS: The scans were assessed for the presence or absence of PSRF or ORFs using en face OCT and cross-sectional B scans by 2 masked graders, with any disagreements adjudicated by a third senior masked grader. MAIN OUTCOME MEASURES: The sensitivity, specificity, and predictive accuracy (using area under the curve [AUC]) of en face OCT were compared with those of cross-sectional OCT, which is considered the gold standard. RESULTS: Two hundred twenty-three patients were included in this study. The Cohen kappa between the graders in the diagnosis of PSRF and ORFs using en face OCT was 0.84 and 0.86, respectively. The sensitivity of en face OCT was 100% (95% confidence interval [CI], 100%-100%) in the diagnosis of PSRF and 98.8% (95% CI, 96.5%-101.1%) in the diagnosis of ORFs. Similarly, the specificity of en face OCT was 98.7% (95% CI, 96.8%-100.5%) and 84.2% (95% CI, 78.1%-90.2%) in the diagnosis of PSRF and ORFs, respectively. The AUC was 0.99 for PSRF and 0.91 for ORFs. CONCLUSIONS: En face OCT has good sensitivity, specificity, and predictive accuracy (using AUC) in the diagnosis of PSRF and ORFs. En face OCT is an efficient screening tool for postoperative anatomic abnormalities, such as PSRF and ORFs, after RRD repair. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A paradigm shift in retinal detachment repair: The concept of integrity.

The management of rhegmatogenous retinal detachment has rapidly evolved over recent decades. A range of surgical techniques exist, all of which can achieve retinal reattachment in most cases. In recent years there have also been vast technical advances in retinal imaging that have introduced novel ways of visualizing and studying the retinal macro and microstructural anatomy following retinal detachment repair. Recent clinical trial data demonstrates that functional and patient-reported outcomes of retinal reattachment differ with surgical technique, accompanied by differences in anatomic biomarkers of retinal recovery or 'integrity'. We discuss recent insights into the physiology of retinal reattachment gleaned from multimodal imaging, which shed light on the pathophysiology of various post-operative anatomic abnormalities. The ideal scenario is to achieve retinal reattachment as soon as possible, without retinal displacement, outer retinal folds or discontinuity of the external limiting membrane, ellipsoid zone and interdigitation zone, with an intact foveal bulge. To this end, we present an in-depth contemporary account of current concepts and mechanisms involved during retinal reattachment surgery, supported by clinical data and mathematical modelling, awareness of which can help the vitreoretinal surgeon achieve better post-operative outcomes. In this review we substantiate the case for a paradigm shift in rhegmatogenous retinal detachment repair; beyond the emphasis on single-operation reattachment rates, and instead striving to maximize functional outcomes using minimally invasive techniques. This can only be achieved if vitreoretinal surgeons embrace all of the available techniques, with individualized selection of surgical approach and the resolute goal of optimizing the 'integrity' of retinal reattachment.

A Case of Morning Glory Disc Associated With Unilateral Retinopathy of Prematurity.

Morning glory disc anomaly is associated with serous retinal detachments, high refractive errors, amblyopia, and strabismus. There have been limited reports of an association between morning glory disc and peripheral retinal non-perfusion. The authors report a case of unilateral morning glory disc anomaly associated with markedly asymmetric retinopathy of prematurity. [J Pediatr Ophthalmol Strabismus. 2022;59(5):e55-e57.].

Retinal displacement following rhegmatogenous retinal detachment: A systematic review and meta-analysis.

Retinal displacement following rhegmatogenous retinal detachment (RRD) repair is an important consideration when assessing the integrity of reattachment, with potential implications on functional outcomes. There are limited data comparing various surgical techniques. We conducted a review of retinal displacement following RRD repair through October 2021, finding 21 studies encompassing 1,258 unique eyes. Outcome measures included the frequency of retinal displacement, visual acuity, metamorphopsia, and displacement direction. A meta-analysis was performed with data reported as risk ratios (RR) or mean difference and 95% confidence intervals. Retinal displacement was found in 35 ± 20% of RRD repairs. Scleral buckle (SB) without tamponade had the lowest rate of retinal displacement, followed by pneumatic retinopexy (PnR) and finally pars plana vitrectomy (PPV) (RR in PPV vs SB: 9.60 [2.01-45.95], P = 0.005). Silicone oil may reduce risk of displacement following PPV compared to gas (RR in gas vs SO: 2.16 [1.22-3.83], P = 0.009), as may immediate face-down positioning for 2 hours. Retinal displacement following PPV occurred in the downward direction in 92 ± 14% of cases and does not appear to significantly impact visual acuity (0.05 [-0.21 to 0.31], P = 0.70), although it may increase distortion. SB, PnR, PPV with silicone oil, and immediate face-down positioning are likely associated with less retinal displacement. Additional prospective studies are required to increase the certainty of these findings.

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.

Longitudinal Assessment of Ellipsoid Zone Recovery Using En Face Optical Coherence Tomography After Retinal Detachment Repair.

PURPOSE: Suboptimal functional outcomes after rhegmatogenous retinal detachment (RRD) repair may be related to photoreceptor abnormalities, including alterations of the ellipsoid zone (EZ) that may not be apparent on cross-sectional optical coherence tomography (OCT). This study assessed EZ recovery using en face OCT after RRD repair and its association with visual acuity. DESIGN: Post hoc analysis of a randomized controlled trial. METHODS: Patients with macula-off RRD were monitored at 3, 6, 12, and 24 months postoperatively and annually thereafter. En face OCT of the EZ slab were analyzed. Hyporeflective areas were colocalized with EZ abnormalities on cross-sectional OCT B-scans and measured by 2 masked graders. Primary outcome was change in area of EZ hyporeflectivity from 3 to 24 months, and its association with Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity recovery was also assessed. RESULTS: In total, 271 images of 61 patients were assessed. Mean area of hyporeflectivity significantly decreased from 3 to 24 months (-2.98 mm2; 95% CI, 1.82-4.13 mm2; P < .0001), with further reductions up to 4 years. Linear regression revealed an association between change in hyporeflective area and change in the ETDRS letter score from 3 to 24 months (ß = -0.31, P = .009, R2 = 14.8%) and between duration of macula-off and change in hyporeflective area from 3 to 24 months (ß = -0.37, P = .018, R2 = 13.7%). CONCLUSIONS: En face OCT provides a novel biomarker for visualizing and quantifying EZ recovery after RRD repair that is associated with ETDRS visual acuity recovery. A steady decline in the area of EZ hyporeflectivity was observed over many years with delayed recovery in patients with longer duration of macula-off.

Outer Retinal Folds after Pars Plana Vitrectomy vs. Pneumatic Retinopexy for Retinal Detachment Repair: Post hoc analysis from PIVOT.

PURPOSE: To assess the incidence of postoperative outer retinal folds (ORFs) after pars plana vitrectomy (PPV) vs. pneumatic retinopexy (PnR) for rhegmatogenous retinal detachment (RRD) repair and to determine the association of ORFs with functional outcomes at 1 year. DESIGN: Randomized controlled trial. PARTICIPANTS: Patients with primary macula-off RRD meeting the Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized (PIVOT) trial criteria who were randomly assigned to undergo PPV or PnR. METHODS: Post hoc analysis of the PIVOT trial. The incidence and quantitative morphologic features of ORFs were assessed using en face and cross-sectional OCT at 1 month postoperatively by 2 masked graders. The ETDRS letter score was measured and quantitative assessment of metamorphopsia was performed at 1 year. MAIN OUTCOME MEASURES: Proportion of patients with ORFs at 1 month postoperatively among those who underwent PPV versus PnR. The secondary outcomes included the association of ORFs with visual acuity (ETDRS letter score) and metamorphopsia via metamorphopsia charts at 12 months postoperatively. RESULTS: Of 176 participants enrolled in PIVOT, 88 were macula-off RRDs. Of them, 94.3% (83 of 88) underwent postoperative OCT scans that were gradable at month 1, 93.2% (41 of 44) in the PPV group and 95.5% (42 of 44) in the PnR group. The incidence of ORF formation was 34.1% (14 of 41) in the PPV group and 14.3% (6 of 42) in the PnR group (P = 0.034). The ETDRS letter score at 1 year was 65.7 ± 6.6 letters in patients with ORFs vs. 75.1 ± 1.4 letters in those without ORFs (difference = 9.4 letters, 95% confidence interval [CI] = 7.5-11.3, P = 0.047). Among patients in the PPV group alone, the mean ETDRS letter score at 1 year in patients with ORFs was 62.8 ± 24.7 letters, compared with 75.4 ± 9.2 letters in patients without ORF formation (difference = 12.6 letters, 95% CI = 0.05-24.59, P = 0.04). Horizontal and vertical metamorphopsia scores were similar in patients with and without ORFs: horizontal, 0.35 ± 0.12 vs. 0.29 ± 0.07 (difference = 0.06, 95% CI = 0.01-0.11, P = 0.69); vertical, 0.25 ± 0.07 vs. 0.29 ± 0.07 (difference = 0.04, 95% CI = 0-0.08, P = 0.60). There was a negative correlation between the closest distance of an ORF from the fovea and vertical metamorphopsia score (r = -0.507, P = 0.045). CONCLUSIONS: There is greater risk of developing ORFs after PPV compared to PnR for primary RRD. Outer retinal folds at 1 month are associated with significantly worse ETDRS visual acuity letter scores at 1 year.