Reticular Pseudodrusen: Interreader Agreement of Evaluation on OCT Imaging in Age-Related Macular Degeneration.

Purpose: To determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence. Design: Interreader agreement study. Participants: Twelve readers from 6 reading centers. Methods: All readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to ≥ 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image. Main Outcome Measures: Interreader agreement, as assessed by Gwet's first-order agreement coefficient (AC1). Results: When evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions, and ≥ 5 definite lesions on en face IR images corresponding to Stage 2 or 3 lesions (AC1 = 0.60-0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions (AC1 = 0.58-0.65) and increasing levels of agreement with increasing RPD stage (AC1 = 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC1 = 0.68), but only fair agreement for this evaluation on selected B-scans (AC1 = 0.30). Conclusions: There was generally substantial or near-substantial-but not near-perfect-agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

OCT Signs of Early Atrophy in Age-Related Macular Degeneration: Interreader Agreement: Classification of Atrophy Meetings Report 6.

PURPOSE: To determine the interreader agreement for incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) and their related features in age-related macular degeneration (AMD). DESIGN: Interreader agreement study. PARTICIPANTS: Twelve readers from 6 reading centers. METHODS: After formal training, readers qualitatively assessed 60 OCT B-scans from 60 eyes with AMD for 9 individual features associated with early atrophy and performed 7 different annotations to quantify the spatial extent of OCT features within regions of interest. The qualitative and quantitative features were used to derive the presence of iRORA and cRORA and also in an exploratory analysis to examine if agreement could be improved using different combinations of features to define OCT atrophy. MAIN OUTCOME MEASURES: Interreader agreement based on Gwet's first-order agreement coefficient (AC1) for qualitatively graded OCT features and classification of iRORA and cRORA, and smallest real difference (SRD) for quantitatively graded OCT features. RESULTS: Substantial or better interreader agreement was observed for all qualitatively graded OCT features associated with atrophy (AC1 = 0.63-0.87), except for RPE attenuation (AC1 = 0.46) and disruption (AC1 = 0.26). The lowest SRD for the quantitatively graded horizontal features was observed for the zone of choroidal hypertransmission (± 190.8 µm). Moderate agreement was found for a 3-category classification of no atrophy, iRORA, and cRORA (AC1 = 0.53). Exploratory analyses suggested a significantly higher level of agreement for a 3-category classification using (1) no atrophy; (2) presence of inner nuclear layer and outer plexiform layer subsidence, or a hyporeflective wedge-shaped band, as a less severe atrophic grade; and (3) the latter plus an additional requirement of choroidal hypertransmission of 250 µm or more for a more severe atrophic grade (AC1 = 0.68; P = 0.013). CONCLUSIONS: Assessment of iRORA and cRORA, and most of their associated features, can be performed relatively consistently and robustly. A refined combination of features to define early atrophy could further improve interreader agreement.

Time to disease recurrence in noninfectious uveitis following long-acting injectable fluocinolone acetonide implant.

PURPOSE: To determine the time to disease recurrence with long-acting injectable fluocinolone acetonide implant (FAi) for noninfectious intermediate, posterior, and panuveitis. METHODS: This was a retrospective study of patients with at least 12 months of follow-up who had completed a 2-year prospective, investigational new drug study with 0.18-mg FAi. Time to uveitis recurrence or cystoid macular edema (CME) occurrence was recorded. RESULTS: Twelve eyes from 12 participants (mean age 43 years, range 25-64 years) were included. Patients were followed for a mean of 34.2 months (range, 12.0-56.9 months) after completion of the prospective trial. Five eyes (42%) did not have a documented uveitis recurrence or CME occurrence. Five eyes (42%) had a uveitis recurrence with the mean time to recurrence 36.1 months (range, 22.8-61.1 months) after FAi implantation. Two eyes (16%) had CME alone, the mean time to occurrence 36.9 months (range 36.1-42.1 months). On Kaplan-Meier analysis, the estimated probability of remaining recurrence-free 36 months after FAi implantation was 0.67 (95% confidence interval, 0.34-0.86). CONCLUSIONS: Data of study participants after completing a clinical trial suggest that the injectable FAi for noninfectious uveitis can provide control for 3 years on average. These long-term data support the use of FAi to control noninfectious uveitis.

Injectable Fluocinolone Acetonide Long-Acting Implant for Noninfectious Intermediate Uveitis, Posterior Uveitis, and Panuveitis: Two-Year Results.

PURPOSE: To determine the effect of an injectable fluocinolone acetonide implant (FAi) in eyes with noninfectious intermediate uveitis, posterior uveitis, or panuveitis. DESIGN: Noncomparative, interventional, dose-randomized, dose-masked, prospective, individual, investigator-sponsored investigational new drug study. PARTICIPANTS: Eleven eyes of 11 participants with a history of recurrent noninfectious intermediate uveitis, posterior, or panuveitis. METHODS: Participants were randomized to receive either a low- or a high-dose FAi. Eyes were observed on day 0 (day the implant was injected) and then at regular intervals through 2 years. MAIN OUTCOME MEASURES: Ocular inflammation, visual acuity, anti-inflammatory medication use, and safety parameters before and after FAi implantation. RESULTS: All participants were followed up for 2 years. At baseline, mean study eye visual acuity was 0.56 logarithm of the minimum angle of resolution (logMAR; standard deviation [SD], 0.43 logMAR). These values improved significantly to +0.25 logMAR (SD, 0.14 logMAR) and +0.17 logMAR (SD, 0.14 logMAR) at 12 and 24 months after implantation, respectively (P = 0.041 and P = 0.016, respectively). The average number of inflammation recurrences in the 12 months before implantation was 1.54 episodes per eye. None of the study eyes experienced a recurrence during the follow-up period. Of the 6 participants who continued receiving systemic medication after implantation, the dosage was reduced in 4 participants. Five of 11 eyes received an average of 1.6 posterior sub-Tenon triamcinolone acetonide (PSTA) injections in the 12 months preceding implantation. None required a PSTA injection after FAi implantation. The most common adverse event was intraocular pressure (IOP) rise. At baseline, 1 study eye (9%) required pressure-lowering drops; 2 additional study eyes (18%) required them during the follow-up period. Filtering procedures were performed in 2 of these eyes (18.1%). No FAi explantations were required, nor were any participants lost to follow-up during the investigation. CONCLUSIONS: It is feasible to place a long-acting FAi in an outpatient setting, without prolonged adverse events attributed to the implant injection procedure. The FAi effectively controlled intraocular inflammation in all eyes in the study, and at the last follow-up, all implanted eyes demonstrated an improvement in visual acuity. Elevated IOP that occurred in 18% of FAi-implanted eyes was managed by standard means. The FAi implant is a promising approach for patients with noninfectious intermediate uveitis, posterior uveitis, or panuveitis who do not respond to, or are intolerant to, conventional therapy.

Long-term follow-up results of a pilot trial of a fluocinolone acetonide implant to treat posterior uveitis.

PURPOSE: To investigate the safety and efficacy of a fluocinolone acetonide intravitreal implant in the treatment of noninfectious posterior uveitis. DESIGN: Noncomparative interventional case series, dose randomized, dose masked, prospective. PARTICIPANTS: Thirty-six eyes of 32 patients with a history of recurrent noninfectious posterior uveitis. METHODS: Patients were randomized to receive either a 0.59-mg or a 2.1-mg fluocinolone acetonide intravitreal implant. Patients were observed every 4 to 6 weeks for the first 3 months and then every 3 months thereafter. MAIN OUTCOME MEASURES: Preoperative and postoperative ocular inflammation, visual acuity (VA), antiinflammatory medication use, and safety. RESULTS: Mean follow-up duration was 683+/-461 days (range, 204-1817). Mean baseline visual acuity for the device-implanted eyes was +1.1 logarithm of the minimum angle of resolution (logMAR) units (20/250), which improved significantly to +0.81 logMAR units (20/125) at 30 months (P<0.05). Inflammation was effectively controlled over the follow-up period. The average number of recurrences in the 12 months before implantation was 2.5 episodes per eye. None of these eyes experienced a recurrence for the first 2 years after implantation. There was a reduction in systemic and local therapy use in the device-implanted eyes; of the patients who remained on systemic medication after implantation, dosage was reduced in 68%. The posterior sub-Tenon's capsule injection rate significantly decreased from a mean of 2.2 injections per eye per year to 0.07 injections per eye per year (P<0.0001) The most common adverse event was intraocular pressure (IOP) rise. At baseline, 11.0% of eyes used pressure-lowering agents, versus 56.1% over the follow-up period (P = 0.005). Filtering procedures were performed in 7 (19.4%) eyes. Four of the 8 phakic eyes, each of which had some level of cataract at device implantation, subsequently underwent cataract extraction. There were no device explantations or patients lost to follow-up during the investigation. CONCLUSION: The fluocinolone acetonide intravitreal implant effectively controlled intraocular inflammation in the studied population. Elevated IOP and cataracts that occurred in fluocinolone device-implanted eyes were managed by standard means. The fluocinolone acetonide sustained drug delivery implant seems to be promising in patients with posterior uveitis who do not respond to or are intolerant to conventional treatment.