BETTER BASELINE VISION LEADS TO BETTER OUTCOMES AFTER THE 0.19-mg FLUOCINOLONE ACETONIDE INTRAVITREAL IMPLANT IN DIABETIC MACULAR EDEMA.

PURPOSE: Analysis of a 3-year, Phase 4, open-label, observational study evaluating the association of baseline best-corrected visual acuity (BCVA) with visual, treatment burden, and retinal thickness variability (RTV) outcomes and intraocular pressure (IOP)-related events after the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant. METHODS: Data from patients with diabetic macular edema (DME) who did not have a clinically significant rise in IOP after previous corticosteroid treatment (N = 202 eyes from 159 patients) were segregated by baseline BCVA of ≥20/40 or <20/40 and analyzed for BCVA, number of yearly supplemental DME treatments, RTV, and incidence of IOP-related events. RESULTS: At 36 months post-FAc, eyes with better baseline BCVA (≥20/40) maintained baseline BCVA, whereas vision in eyes with worse baseline BCVA (<20/40) increased by approximately 7 letters to 61.34 letters (Snellen equivalent approximately 20/60; P < 0.05). Treatment burden and RTV decreased post-FAc regardless of baseline BCVA. Eyes with better baseline BCVA (≥20/40) had numerically fewer IOP-related events post-FAc versus eyes with worse baseline BCVA (<20/40), including a lower incidence of incisional IOP-lowering surgery. CONCLUSION: The 0.19-mg FAc implant improved RTV and treatment burden regardless of baseline BCVA. Better baseline BCVA (≥20/40) was associated with long-term BCVA maintenance. Although eyes with worse baseline BCVA (<20/40) experienced significantly improved BCVA, it never rose to the level of those with better baseline BCVA. These data indicate that early, effective intervention in DME, before significant vision loss occurs, is key to maintaining visual outcomes.

The 0.19-mg Fluocinolone Acetonide Implant for the Treatment of Diabetic Macular Edema: An Expert Consensus.

BACKGROUND AND OBJECTIVE: To better understand the level of agreement among retina specialists on the role of inflammation in diabetic retinopathy (DR) and diabetic macular edema (DME), and the use of 0.19-mg fluocinolone acetonide (FAc) implant in DME treatment, a consensus survey was drafted and disseminated to retina specialists across the United States. MATERIALS AND METHODS: Using the modified Delphi method, a list of 12 consensus statements were generated by the coauthors based on short-answer responses to an initial survey. In total, 56 retina specialists completed the entire consensus survey. Except for two multiple-choice questions, there were 10 consensus statements that used a modified Likert scale to indicate their level of agreement to the statement: Agree = 3, Mostly Agree = 2, Mostly Disagree = 1, Disagree = 0. Percentage agreement and 95% confidence intervals (CIs) were calculated, and a consensus threshold was set at > 80% agreement for each statement. RESULTS: Seven of 10 consensus statements using the modified Likert scale reached consensus, including those on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. The remaining three statements displayed high agreement with average scores > 80%, but the 95% CIs were below threshold. These included the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. Two multiple-choice questions focused on clinical situations in which corticosteroids would be used as baseline therapy for DME (pseudophakic eye [73%], recent stroke/myocardial infarction [66%], and pregnancy/breastfeeding [66%]) and which delivery route satisfies the steroid challenge for the FAc implant (intravitreal [100%], sub-tenon/periocular [73%], and topical [57%]). CONCLUSIONS: Physicians highly agreed on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. However, full consensus was not found on the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. [Ophthalmic Surg Lasers Imaging Retina. 2023;54(3):166-173.].

Sustained-release Low-dose Fluocinolone Acetonide Intravitreal Implant for Chronic Postoperative Cystoid Macular Edema: Two Case Reports.

PURPOSE: To describe two cases of patients diagnosed with chronic postoperative cystoid macular edema associated with non-infectious posterior uveitis who had limited treatment response to previous corticosteroid modalities and then received a single intravitreal fluocinolone 0.18 mg implant. METHODS: Series of two case reports. RESULTS: Compared to baseline, both patients experienced resolution of their disease symptoms, >3 lines of visual acuity improvement, and macular edema reduction of 56.2 and 38.4% and 15 and 6 months respectively, following the fluocinolone implant. No steroid-related adverse events including any intraocular pressure measurement >25 mm Hg were observed. CONCLUSION: A single intravitreal fluocinolone 0.18mg implant can effectively and safely treat vision loss and increased central macular thickness due to chronic postoperative cystoid macular edema associated with non-infectious posterior uveitis.

Assessing the impact of privacy-preserving record linkage on record overlap and patient demographic and clinical characteristics in PCORnet®, the National Patient-Centered Clinical Research Network.

OBJECTIVE: This article describes the implementation of a privacy-preserving record linkage (PPRL) solution across PCORnet®, the National Patient-Centered Clinical Research Network. MATERIAL AND METHODS: Using a PPRL solution from Datavant, we quantified the degree of patient overlap across the network and report a de-duplicated analysis of the demographic and clinical characteristics of the PCORnet population. RESULTS: There were ∼170M patient records across the responding Network Partners, with ∼138M (81%) of those corresponding to a unique patient. 82.1% of patients were found in a single partner and 14.7% were in 2. The percentage overlap between Partners ranged between 0% and 80% with a median of 0%. Linking patients' electronic health records with claims increased disease prevalence in every clinical characteristic, ranging between 63% and 173%. DISCUSSION: The overlap between Partners was variable and depended on timeframe. However, patient data linkage changed the prevalence profile of the PCORnet patient population. CONCLUSIONS: This project was one of the largest linkage efforts of its kind and demonstrates the potential value of record linkage. Linkage between Partners may be most useful in cases where there is geographic proximity between Partners, an expectation that potential linkage Partners will be able to fill gaps in data, or a longer study timeframe.

Establishing a framework for privacy-preserving record linkage among electronic health record and administrative claims databases within PCORnet®, the National Patient-Centered Clinical Research Network.

OBJECTIVE: The aim of this study was to determine whether a secure, privacy-preserving record linkage (PPRL) methodology can be implemented in a scalable manner for use in a large national clinical research network. RESULTS: We established the governance and technical capacity to support the use of PPRL across the National Patient-Centered Clinical Research Network (PCORnet®). As a pilot, four sites used the Datavant software to transform patient personally identifiable information (PII) into de-identified tokens. We queried the sites for patients with a clinical encounter in 2018 or 2019 and matched their tokens to determine whether overlap existed. We described patient overlap among the sites and generated a "deduplicated" table of patient demographic characteristics. Overlapping patients were found in 3 of the 6 site-pairs. Following deduplication, the total patient count was 3,108,515 (0.11% reduction), with the largest reduction in count for patients with an "Other/Missing" value for Sex; from 198 to 163 (17.6% reduction). The PPRL solution successfully links patients across data sources using distributed queries without directly accessing patient PII. The overlap queries and analysis performed in this pilot is being replicated across the full network to provide additional insight into patient linkages among a distributed research network.

Home Monitoring of Age-Related Macular Degeneration: Utility of the ForeseeHome Device for Detection of Neovascularization.

PURPOSE: To evaluate the real-world utility of the ForeseeHome monitoring device (Notal Vision, Ltd., Tel Aviv, Israel) for the detection of conversion from intermediate age-related macular degeneration (iAMD) to neovascular AMD (nAMD) and to compare with results published by the Home Monitoring of the Eye (HOME) study. DESIGN: Retrospective analysis of electronic health records. PARTICIPANTS: Eyes prescribed use of the ForeseeHome device across 4 retinal practices in the United States. METHODS: Usage information was collected from the online ForeseeHome portal for all eyes prescribed the device. For a predetermined subset of eyes, additional clinical information was collected through chart review and analyzed for clinical utility. MAIN OUTCOME MEASURES: Frequency and length of use, number of eyes that used the device, number of eyes that established a baseline measurement, number of eyes that converted to nAMD, and number of alerts. RESULTS: Seven hundred seventy-five eyes of 448 patients were prescribed use of the ForeseeHome device. Six hundred forty-nine eyes (83.7%) used the device at least once; among this population, 478 (73.7%) established a baseline measurement. Patients who established a baseline measurement were significantly younger than those who did not (P < 0.001). Among eyes that established a baseline measurement, 126 (26.4%) had an overall inadequate frequency of use (≥2 tests per week), and 250 (52.3%) did not use the device as frequently as instructed by the manufacturer (≥3 tests per week); 24.7% of eyes discontinued use within 1 year. Of the 136 eyes that established a baseline measurement among 211 eyes prescribed the device at 1 clinical site, 52 alerts were recorded; 3 (6.8%) correctly identified conversion to nAMD and 47 (93.2%) represented false-positive alerts. CONCLUSIONS: Compared with the prospective HOME study, the utility of the ForeseeHome device in the current analysis of clinical practice application was limited. A meaningful proportion of eyes never used the device or could not establish a baseline measurement. Overall frequency of use was low, and continuous use of the device decreased over time. A need exists for improvement in home monitoring technology for eyes with iAMD at risk of conversion to nAMD.

Two-year interim safety results of the 0.2 µg/day fluocinolone acetonide intravitreal implant for the treatment of diabetic macular oedema: the observational PALADIN study.

BACKGROUND: The 0.2 µg/day fluocinolone acetonide (FAc) implant delivers continuous, low-dose, intravitreal corticosteroid for the treatment of diabetic macular oedema (DMO). This ongoing, 3-year, observational clinical trial provides long-term, 'real-world' safety results for the FAc implant in DMO. METHODS: This 24-month interim analysis of a prospective, observational study investigated patients with DMO receiving the commercially available intravitreal 0.2 µg/day FAc implant. The primary outcome was incidence of intraocular pressure (IOP)-lowering procedures. Other IOP-related signals and their relationship to previous corticosteroid exposure, best-corrected visual acuity, central subfield thickness (CST), ocular adverse events and frequency of other treatments were also measured. RESULTS: Data were collected from 95 previously steroid-challenged patients (115 study eyes) for up to 36 months pre-FAc and 24 months post-FAc implant. Mean IOP for the overall population remained stable post-FAc compared with pre-FAc implant. IOP-related procedures remained infrequent (two IOP-lowering surgeries pre-FAc; two trabeculoplasties and four IOP-lowering surgeries post-FAc). Mean visual acuity was stable post-FAc (mean improvement of 1-3 letters) and fewer DMO treatments were required per year following FAc implant. Mean CST was significantly reduced at 24 months post-FAc implant (p<0.001) and the percentage of patients with CST ≤300 µm was significantly increased (p=0.041). CONCLUSION: Few IOP-related procedures were reported during the 24 months post-FAc implant. Positive efficacy outcomes were noted after treatment, with stabilisation of vision and reduction in inflammation, demonstrated by CST. The FAc implant has a favourable benefit-risk profile in the management of DMO, especially when administered after a prior steroid challenge. TRIAL REGISTRATION NUMBER: NCT02424019.

Dexamethasone intracameral drug-delivery suspension for inflammation associated with vitreoretinal surgery.

OBJECTIVE: To evaluate the efficacy of an anterior chamber intracameral dexamethasone (ICD) drug-delivery suspension (Dexycu; EyePoint Pharmaceuticals, Watertown, Massachusetts, USA) providing sustained release of medication following a single application for the treatment of postoperative inflammation in patients undergoing vitreoretinal surgery compared to daily postoperative treatment with topical corticosteroids for up to 1 month. METHODS AND ANALYSIS: Retrospective case-matched comparison of patients undergoing initial vitreoretinal surgery by a single surgeon. Patients had a preoperative best-corrected visual acuity of 20/20 to light perception and a variety of vitreoretinal pathologies. 27 eyes of 27 patients received ICD at the time of surgery and were compared with 27 eyes of 27 patients who received daily postoperative corticosteroid eye drops over 4 weeks. The primary efficacy outcome was anterior chamber cell (ACC) clearing (0 cells) in the study eye at postoperative day (POD) 7. Ocular adverse events were assessed through POD 90. RESULTS: ACC clearing at POD 7 was achieved in 67% of eyes in the ICD treatment group and 37% of eyes in the control group treated with topical corticosteroids (p=0.029). No serious ocular adverse events were noted up to POD 90 in either group. CONCLUSION: The ICD drug-delivery suspension placed in the anterior chamber after vitreoretinal surgery was more effective than topical corticosteroids in treating inflammation occurring 1 week following vitreoretinal surgery and thus may be an alternative to daily corticosteroid drop installation in this patient population.

Longitudinal analysis of the structural pattern of pseudophakic cystoid macular edema using multimodal imaging.

PURPOSE: To describe the relationship between pseudophakic cystoid macular edema (CME) progression and retinal structural changes observed by spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography. METHODS: Retrospective, consecutive, longitudinal imaging analysis of patients with acute pseudophakic cystoid macular edema. Two observers at two study centers evaluated all images and categorized the macular structural features based on the retinal layer involved with cystic changes and/or subretinal fluid. A time series of the structural pattern and visual acuity was constructed for 1-month intervals over a 6-month study period. RESULTS: Thirty nine patients presented with CME. The mean time since cataract extraction was 48 ±38 days (range 5-71). CME included inner nuclear layer (INL) cystic changes, outer plexiform layer (OPL) cystic changes, and subretinal fluid. Isolated INL changes were observed in four phakic fellow eyes. Isolated OPL morphology was not observed, and additional inner layers remained uninvolved. Resolution occurred rapidly following administration of periocular glucocorticoids, and typically demonstrated a reverse structural pattern or delayed subretinal fluid resolution. Isolated subretinal fluid or a combined INL and subretinal fluid structure indicated CME resolution. CONCLUSION: Acute and recurrent pseudophakic CME involves a directional progression of the retinal layer involved with cystic changes and a clinical course. CME begins with INL cystic changes, progresses to combined INL and OPL morphology, and may continue to involve subretinal fluid. The inner nuclear layer is the most frequently involved layer, and isolated INL cysts may occur in phakic fellow eyes. A three-layer structure, the presence of OPL morphology, or isolated INL early in the postoperative period indicates disease activity.

Outcomes of chronic macular hole surgical repair.

PURPOSE: To report visual and anatomic outcomes of chronic macular hole surgery, with analysis of pre-operative OCT-based hole size and post-operative closure type. SETTINGS AND DESIGN: An IRB-approved, retrospective case series of 26 eyes of 24 patients who underwent surgery for stage 3 or 4 idiopathic chronic macular holes at a tertiary care referral center. STATISTICAL ANALYSIS: Student's t-test. RESULTS: Nineteen of 26 eyes (73%) had visual improvement after surgery on most recent exam. Twenty-one of 26 eyes (81%) achieved anatomic closure; 16 of 26 eyes (62%) achieved type 1, and five of 26 eyes (19%) achieved type 2 closure. Post-operative LogMAR VA for type 1 closure holes (0.49) was significantly greater than for type 2 closure and open holes (1.26, P < 0.003 and 1.10, P < 0.005, respectively), despite similar pre-operative VA (P = 0.51 and 0.68, respectively). Mean pre-operative hole diameter for eyes with type 1 closure, type 2 closure, and holes that remained open were 554, 929, and 1205 microns, respectively. Mean pre-operative hole diameter was significantly larger in eyes that remained open as compared to eyes with type 1 closure (P = 0.015). CONCLUSION: Vitrectomy to repair chronic macular holes can improve vision and achieve long-term closure. Holes of greater than 3.4 years duration were associated with a greater incidence of remaining open and type 2 closure. Larger holes (mean diameter of 1205 microns) were more likely to remain open after repair.

Peripheral nonperfusion and tractional retinal detachment associated with congenital optic nerve anomalies.

PURPOSE: To report an association of congenital optic nerve anomalies with peripheral retina nonperfusion and to describe the clinical manifestations and treatment. DESIGN: Retrospective, observational case series. PARTICIPANTS: Fifteen patients with congenital optic nerve anomalies referred for pediatric retina consultation were studied. Sixteen eyes of 9 patients with optic nerve hypoplasia and 8 eyes of 6 patients with other congenital optic nerve anomalies, including optic nerve coloboma, morning glory disc, and peripapillary staphyloma, were included. METHODS: All patients underwent examinations under anesthesia. Wide-angle retina photographs and fluorescein angiograms were reviewed. The severity of nonperfusion was graded. The presence of fibrovascular proliferation (FP), vitreous hemorrhage (VH), and tractional retinal detachment (TRD) were documented. Anatomic outcome after treatment was recorded. MAIN OUTCOME MEASURES: Severity of nonperfusion, occurrence of secondary complications, and the anatomic outcome of patients who underwent laser treatment. RESULTS: In patients with optic nerve hypoplasia, 12 of 16 eyes (75%) had severe peripheral nonperfusion, 12 of 16 eyes (75%) had FP, 3 of 16 eyes (19%) had VH, and 10 of 16 eyes (63%) had TRD. Six of these eyes with severe nonperfusion received laser photocoagulation to the nonperfused retina; laser-treated retinas remained attached in all 6 eyes. In patients with the other optic nerve anomalies, 7 of 8 eyes (88%) had mild to moderate nonperfusion, 2 of 8 eyes (25%) had FP, 1 of 8 eyes (12%) had VH, and 2 of 8 eyes (25%) had TRD. Six of 9 patients (67%) with optic nerve hypoplasia and 1 of 6 patients (17%) with other anomalies had a coexisting congenital brain disease. CONCLUSIONS: Congenital optic nerve anomalies may be associated with peripheral retina nonperfusion and the secondary complications of FP, VH, and TRD. In this select group of patients, the nonperfusion associated with optic nerve hypoplasia seemed to be more severe and associated more frequently with secondary complications. Peripheral retina examination in eyes with optic nerve anomalies may identify nonperfusion or FP. Laser treatment of the avascular retina may have helped prevent complications from proliferative retinopathy in eyes clinically observed to have progressed or considered at risk for progression to proliferative retinopathy.

Intraocular corticosteroids for posterior segment disease: 2012 update.

INTRODUCTION: Diabetic macular edema (DME), cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO) and uveitis are responsible for severe visual impairment worldwide. In some patients with these conditions, treatment with intraocular corticosteroids may be beneficial. Although off-label use of these agents has occurred for many years, novel agents including preservative-free and sustained-release intravitreal implants are currently being studied in clinical trials (CTs). AREAS COVERED: This paper reviews the use of CTs for vitreoretinal (VR) diseases including choroidal neovascularization, CME, DME, RVO and posterior uveitis. It also discusses the use of corticosteroids for treating VR disease, including dexamethasone, fluocinolone acetonide, intravitreal implants and triamcinolone acetonide. EXPERT OPINION: Used alone, intravitreal corticosteroids may benefit disorders such as DME, RVO and uveitis compared with standard therapy. Cases of exudative AMD non-responsive to standard treatment may benefit from combination therapy, including usage of intravitreal corticosteroid injections. Intraoperative use of these agents may aid visualization of retinal structures. Sustained-release intraocular implants have been approved for posterior uveitis and RVO associated with macular edema. In spite of this, most intraocular corticosteroids have a limited duration of action along with significant side effects, including cataract and glaucoma. Currently, intravitreal corticosteroid usage for DME is considered off-label.

En face spectral-domain optical coherence tomography outer retinal analysis and relation to visual acuity.

PURPOSE: To describe a method of en face visualization and quantification of the photoreceptor inner segment/outer segment junction area, using spectral-domain optical coherence tomography, and association with visual acuity. METHODS: Case series of 74 eyes in 53 patients. Central 1-mm and 400-µm en face areas were analyzed with a computer algorithm. RESULTS: The presence or absence of inner segment/outer segment junction was visible on both spectral-domain optical coherence tomography en face and retinal cross sections. Thirty eyes (40.6%) had no retinal pathology and an average logMAR visual acuity of 0.116. Twenty-five eyes (33.8%) had intraretinal edema, with visual acuity of 0.494. Nineteen eyes had nonneovascular age-related macular degeneration (dry age-related macular degeneration, 25.6%), with visual acuity of 0.392. In all eyes, central 1-mm and 400-µm en face areas were 58.3 ± 25.0% and 56.4 ± 26.0%, which showed significant correlation with visual acuity (Pearson correlation, r = -0.66 and -0.56, both P < 0.001). This correlation was greater than correlation of visual acuity with central subfield thickness (r = 0.39, P < 0.001), macular volume (r = 0.36, P = 0.002), and average macular thickness (r = 0.37, P = 0.001). However, no variables were significantly correlated with dry age-related macular degeneration eyes. CONCLUSION: Central en face inner segment/outer segment junction areas are significantly correlated with visual acuity in most eyes. This may correlate better with visual acuity than other spectral-domain optical coherence tomography values, as a reflection of photoreceptor integrity. Dry age-related macular degeneration may disrupt the plane used to formulate the en face display. Advancements in spectral-domain optical coherence tomography may provide routine en face visualization analysis.

Vitreomacular adhesion associated with foveal-sparing preretinal hemorrhage.

PURPOSE: To report two cases of central macular sparing of subhyaloid hemorrhages secondary to vitreomacular adhesion documented by spectral-domain ocular coherence tomography findings. METHODS: Review of two patients with subhyaloid hemorrhage secondary to proliferative diabetic retinopathy and a macroaneurysm were performed. Treatment was not performed in either patient for management of the hemorrhage, but the patient with proliferative diabetic retinopathy was treated with panretinal photocoagulation for peripheral neovascularization. Foveal sparing of the hemorrhage was documented clinically and on spectral-domain ocular coherence tomography. RESULTS: In Case 1, the proliferative diabetic retinopathy was stabilized with 2 rounds of panretinal photocoagulation treatment, and the visual acuity improved to 20/20 in the affected left eye after 8 months of observation. In Case 2, the visual acuity returned to baseline at 20/60 after 4 months of observation. CONCLUSION: Macular involvement of subhyaloid hemorrhages may cause visual impairment, but vitreomacular adhesion may block the hemorrhage from obstructing the fovea.

Thirty-Year follow-up of an African American family with macular dystrophy of the retina, locus 1 (North Carolina macular dystrophy).

PURPOSE: To describe clinical characteristics, including visual acuity (VA), genetic analysis, and management of complications, over a 30-year period in an African American family with macular dystrophy of the retina, locus 1 (MCDR1), commonly referred to as "North Carolina macular dystrophy." DESIGN: Observational, cohort study. PARTICIPANTS: Twelve family members from a 4-generation pedigree. METHODS: A total of 12 African American patients in an affected family were examined. Clinical examination was documented during 2 different follow-up periods from 1979 to 1982 in 10 patients and from 2005 to 2009 in 11 patients. Genetic analysis was performed in 4 affected members during this time. Foveal microperimetry, fundus autofluorescence, and spectral domain optical coherence tomography (OCT) data were also obtained. MAIN OUTCOME MEASURES: Change in VA of 8 members followed over 3 decades and clinical data and management of complications for all patients. RESULTS: Nine of 11 living family members had classic findings ranging from disease grade 2 (confluent foveal drusen, 8 eyes) to grade 3 (central coloboma-like lesion, 10 eyes). Two members developed choroidal neovascularization (CNV) requiring laser ablation, and 1 member developed non-clearing vitreous hemorrhage and underwent 25-gauge pars plana vitrectomy. Another family member developed exotropia and amblyopia in 1 eye by age 7 years. Those without CNV had no significant change in VA over 30 years. Linkage studies of 4 affected family members showed the same short tandem repeats on markers spanning D6S249 and D6S283 within the MCDR1 region of chromosome 6q16. Microperimetry analysis of an affected member with grade 3 MCDR1 revealed absent function in the region of the central coloboma-like lesions, corresponding to photoreceptor absence on OCT, although there were preserved foveal function and intact photoreceptors adjacent to the lesion. CONCLUSIONS: This African American family shares similar clinical findings as other MCDR1 pedigrees and the same haplotype as the originally described family from North Carolina. Clinical characteristics, including retinal features and stable VA in the absence of amblyopia and CNV, are similar to those in other reports. Eccentric viewing around impaired photoreceptors may explain good VA in patients with clinically severe-appearing macular lesions. Sequencing of the MCDR1 interval may help identify a protein responsible for early macular development. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.