Small-Gauge Vitrectomy for Macular Surgery Using a Systematic Approach to Wound Closure: 27-Gauge vs 25-Gauge.

Purpose: To evaluate the effectiveness of and to compare vitrectomy performed with 25-gauge or 27-gauge instrumentation for macular surgery by assessing the surgical duration, wound closure, and complication rate using a systematic approach to wound closure. Methods: In this retrospective chart review, 125 25-gauge and 125 27-gauge consecutive small-gauge vitrectomy surgeries for epiretinal membrane, macular hole, vitreomacular adhesion, or a combination were analyzed during and immediately after surgery. Wound closure was performed using a systematic protocol. Results: Baseline characteristics were not statistically different between the 2 groups. The surgical duration was similar with 25-gauge vitrectomy and 27-gauge vitrectomy (P = .07). Although spontaneous wound closure was common in both groups, it was more common in the 27-gauge group (P = .22). Intraoperative and postoperative complications were uncommon in both groups. Conclusions: Findings show that 27-gauge vitrectomy is a safe, effective alternative to the more commonly used 25-gauge vitrectomy for macular surgery. Less manipulation was required to achieve wound closure with 27-gauge vitrectomy using a standardized wound-closure protocol. Smaller 27-gauge vitrectomy did not increase surgical time or complications over 25-gauge vitrectomy for macular surgery.

Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial.

BACKGROUND: Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth. METHODS: GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic institutions globally. To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad pegol 2 mg administered as a 100 µL intravitreal injection or sham for the first 12 months. Randomisation was performed using an interactive response technology system with stratification by factors known to be of prognostic importance in age-related macular degeneration. Patients, investigators, study centre staff, sponsor personnel, and data analysts were masked to treatment allocation. The primary endpoint was geographic atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and month 12. Efficacy and safety analyses were done in the modified intention-to-treat and safety populations, respectively. This trial is registered with ClinicalTrials.gov, NCT04435366. FINDINGS: Between June 22, 2020, and July 23, 2021, 1422 patients were screened for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol 2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study treatment and was excluded from analyses. There were 154 (68%) female patients and 71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female patients and 66 (30%) male patients in the sham group. From baseline to month 12, the mean rate of square-root-transformed geographic atrophy area growth was 0·336 mm/year (SE 0·032) with avacincaptad pegol 2 mg and 0·392 mm/year (0·033) with sham, a difference in growth of 0·056 mm/year (95% CI 0·016-0·096; p=0·0064), representing a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular treatment-emergent adverse events in the study eye occurred in 110 (49%) patients in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over 12 months. To month 12, macular neovascularisation in the study eye occurred in 15 (7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group, with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad pegol 2 mg group and seven (3%) in the sham group. INTERPRETATION: Monthly avacincaptad pegol 2 mg was well tolerated and showed significantly slower geographic atrophy growth over 12 months than sham treatment, suggesting that avacincaptad pegol might slow disease progression and potentially change the trajectory of disease for patients with geographic atrophy. FUNDING: Iveric Bio, An Astellas Company.

High-Dose Aflibercept for Neovascular AMD and DME in Suboptimal Responders to Standard-Dose Aflibercept.

Purpose: To assess the effect of higher dose (HD) aflibercept on visual acuity (VA), optical coherence tomography outcomes, and injection burden in eyes with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) that responded suboptimally to standard-dose aflibercept. Methods: This retrospective analysis included eyes with clinically significant disease activity on monthly therapy (AMT) (injection interval ≤35 days) or clinically significant increased activity on extension (IAE) (injection interval >36 days) that were switched from aflibercept 2 mg to aflibercept HD (3 mg to 4 mg). Outcomes were assessed at baseline, after injections 1 through 4, and at 6, 9, and 12 months. Results: Overall, 318 eyes of 288 adult patients were analyzed (eyes with nAMD: 59 AMT, 147 IAE; eyes with DME: 50 AMT, 62 IAE). Most of the study cohort received aflibercept HD 3 mg (nAMD: 73% AMT and 58% IAE; DME: 49% AMT and 68% IAE); the remainder received 4 mg. The mean best VA improved significantly with AMT and was maintained with IAE. In all groups, the central subfield thickness decreased significantly and the mean injection intervals increased or remained stable. No new safety signals were observed. Conclusions: Aflibercept HD might improve outcomes while decreasing treatment burden for eyes that respond suboptimally to standard dosing.

DEFINING "STRONG" VERSUS "WEAK" RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR CENTER-INVOLVED DIABETIC MACULAR EDEMA.

BACKGROUND/PURPOSE: To define "strong" versus "weak" antivascular endothelial growth factor (anti-VEGF) treatment response in eyes with center-involved diabetic macular edema (CI-DME). METHODS: Exploratory analyses of three DRCR Retina Network randomized trials of eyes with CI-DME treated with aflibercept, bevacizumab, or ranibizumab. Thresholds of 5-, 10-, and 15-letter gain defined strong visual acuity (VA) response when baseline VA was 20/25-20/32, 20/40-20/63, or 20/80-20/320, respectively. Thresholds of 50, 100, or 200- µ m reduction defined strong anatomical response when baseline central subfield thickness (CST) was <75, ≥75 to <175, or ≥175- µ m above standard thresholds. Additional thresholds from regression equations were calculated. RESULTS: At 24 weeks, outcomes for strong response were achieved by 476 of 958 eyes (50%) for VA and 505 eyes (53%) for CST. At 104 weeks among the 32% of eyes with strong VA and CST response at 24 weeks, 195 of 281 (69%) maintained strong VA and CST response, whereas 20 (7%) had neither strong VA nor strong CST response. Outcomes rates were similar across protocols and when defined using regression equations. CONCLUSION: These phenotypes are suitable for efforts to identify predictive biomarkers for response to anti-VEGF therapy for DME and might facilitate comparison of treatment response among diverse cohorts with DME.

Implantation Site of a Port Delivery System With Ranibizumab: Anterior Segment Optical Coherence Tomography Evaluation.

Purpose: To determine whether anterior segment optical coherence tomography (AS-OCT) can be used to obtain noninvasive high-resolution images for monitoring the implantation site of a port delivery system with ranibizumab (PDS). Methods: Six eyes from the Archway phase 3 trial were imaged with AS-OCT after surgical implantation of the PDS and at regular follow-up visits. Results: AS-OCT was helpful in monitoring the status of the overlying conjunctiva and Tenon capsule after implantation of the PDS. Minimal qualitative thinning was observed over the implants at the longest follow-up. No cases of conjunctival erosion were noted. Conclusions: AS-OCT can be used to help to monitor PDS implants and potential associated complications.

Conversion of Central Subfield Thickness Measurements of Diabetic Macular Edema Across Cirrus and Spectralis Optical Coherence Tomography Instruments.

Purpose: Develop equations to convert Cirrus central subfield thickness (CST) to Spectralis CST equivalents and vice versa in eyes with diabetic macular edema (DME). Methods: The DRCR Retina Network Protocol O data were split randomly to train (70% sample) and validate (30% sample) conversion equations. Data from an independent study (CADME) also validated the equations. Bland-Altman 95% limits of agreement between predicted and observed values evaluated the equations. Results: Protocol O included 374 CST scan pairs from 187 eyes (107 participants). The CADME study included 150 scan pairs of 37 eyes (37 participants). Proposed conversion equations are Spectralis = 40.78 + 0.95 × Cirrus and Cirrus = 1.82 + 0.94 × Spectralis regardless of age, sex, or CST. Predicted values were within 10% of observed values in 101 (90%) of Spectralis and 99 (88%) of Cirrus scans in the validation data; and in 136 (91%) of the Spectralis and 148 (99%) of the Cirrus scans in the CADME data. Adjusting for within-eye correlations, 95% of conversions are estimated to be within 17% (95% confidence interval, 14%-21%) of CST on Spectralis and within 22% (95% confidence interval, 18%-28%) of CST on Cirrus. Conclusions: Conversion equations developed in this study allow the harmonization of CST measurements for eyes with DME using a mix of current Cirrus and Spectralis device images. Translational Relevance: The CSTs measured on Cirrus and Spectralis devices are not directly comparable owing to outer boundary segmentation differences. Converting CST values across spectral domain optical coherence tomography instruments should benefit both clinical research and standard care efforts.

Optimizing Anti-VEGF Treatment Outcomes for Patients with Neovascular Age-Related Macular Degeneration.

BACKGROUND: The introduction of anti-vascular endothelial growth factor (anti-VEGF) drugs to ophthalmology has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). Despite this significant progress, gaps and challenges persist in the diagnosis of nAMD, initiation of treatment, and management of frequent intravitreal injections. Thus, nAMD remains a leading cause of blindness in the United States. OBJECTIVE: To present current knowledge, evidence, and expert perspectives on anti-VEGF therapies in nAMD to support managed care professionals and providers in decision making and collaborative strategies to overcome barriers to optimize anti-VEGF treatment outcomes among nAMD patients. SUMMARY: Three anti-VEGF therapies currently form the mainstay of treatment for nAMD, including 2 therapies approved by the FDA for treatment of nAMD (aflibercept and ranibizumab) and 1 therapy approved by the FDA for oncology indications and used off-label for treatment of nAMD (bevacizumab). In clinical trials, each of the 3 agents maintained visual acuity (VA) in approximately 90% or more of nAMD patients over 2 years. However, in long-term and real-world settings, significant gaps and challenges in diagnosis, treatment, and management pose barriers to achieving optimal outcomes for patients with nAMD. Many considerations, including individual patient characteristics, on-label versus off-label treatment, repackaging, and financial considerations, add to the complexity of nAMD decision making and management. Many factors may contribute to additional challenges leading to suboptimal long-term outcomes among nAMD patients, such as delays in diagnosis and/or treatment approval and initiation, individual patient response to different anti-VEGF therapies, lapses in physician regimentation of anti-VEGF injection and monitoring, and inadequate patient adherence to treatment and monitoring. These latter factors highlight the considerable logistical, emotional, and financial burdens of long-term, frequent intravitreal injections and the vital importance of personalized approaches to anti-VEGF treatment decision making and management for patients with nAMD. To address these challenges and reduce the number of yearly injections, studies have examined alternative dosing regimens, including extended fixed intervals, as needed, and treat-and-extend strategies in specific nAMD patient populations. New clinical evidence and insights into expert clinical practice discussed in this article can support managed care professionals in the key role they play in addressing challenges in nAMD treatment and management and optimizing patient outcomes through appropriate management of anti-VEGF treatment. DISCLOSURES: PRIME Education is an independent medical education company and has been an accredited provider of continuing education for 23 years. There is no fee for this activity as it is sponsored by PRIME through an educational grant from Regeneron. All authors contributed to the writing and reviewing of the article. Wykoff reports consultancies/research grants from Alcon Laboratories, Genentech/Roche, Clearside, and Iconic Therapeutics; consultancies/honoraria, research grants, and speaker fees from Allergan and Regeneron; research grants from Allegro, Apellis, Aura, NEI, NIH, Novartis, OHR Pharmaceuticals, Ophthotech, pSivida, Roche, Santen, SciFluor, Tyrogenex; and consultancies for Alimera Sciences, Alnylam Pharmaceuticals, Bayer, DORC, ONL Therapeutics, Thrombogenics, and Valeant. Clark reports advisory board work, consultancies, research grants, and speaker fees from Genentech/Roche and Regeneron and consultancy for Bayer. Brill reports consultancies for Aries Pharma, Avella, BaroNova, Braeburn Pharmaceuticals, Cardinal Health, Endogastric Solutions, GeneNews, Halt Medical, Lumendi, Medtronic, Monteris Medical, Natera, Phosphorus, Rebiotix, Seno Medical, UCB, Vermillion, Echosens, and HAP Innovations. Brill is a shareholder in EndoChoice, GeneNews, SonarMD, and SynerZ and reports advisory board work with Nestle Health Sciences, Indivior Pharmaceuticals, Eli Lilly, Blue Earth Diagnostics, Bayer, and AstraZeneca. Nielson reports advisory board work/consultancy and research grants for Genentech/Roche; advisory board work and research grants from Regeneron; and research grants from Alcon and Ophthotech.

Multimodal imaging of white and dark without pressure fundus lesions.

PURPOSE: To describe multimodal imaging findings in patients with dark or white without pressure lesions of the fundus. METHODS: Retrospective observational case series of 10 patients with white or dark without pressure lesions. We analyzed multimodal imaging using spectral domain optical coherence tomography, color and near-infrared fundus photography, and fundus autofluorescence imaging to explore the findings associated with these lesions. RESULTS: All patients had geographic dark or white lesions on clinical examination and color photography, which were either hyporeflective or hyperreflective on near-infrared reflectance imaging, respectively. On optical coherence tomography, these lesions correlated with an abrupt change of the photoreceptor reflectivity, with relative hyporeflectivity of photoreceptor zones (ellipsoid and interdigitation zones, as well as outer segments) within the dark, and relative hyperreflectivity within white lesions. Ten patients underwent fundus autofluorescence, which showed well-defined zones of relative hypo-autofluorescence within the lesion, compared with neighboring uninvolved regions, whether dark or white without pressure. In two patients who had a lesion combining white and dark without pressure, we observed the transition in photoreceptor reflectivity from the dark lesion (hyporeflective) to the white lesion (hyperreflective), relative to the surrounding retina. CONCLUSION: Both white and dark without pressure lesions are associated with changes in outer retinal reflectivity on optical coherence tomography, which occur in opposite directions compared with the surrounding unaffected areas. In the face of normal visual field testing to date, the clinical significance of this finding remains uncertain. Recognition of the optical coherence tomography appearance will help clinicians avoid unnecessary workup of these patients for outer retinal dystrophy or degeneration.

Rifampin induced hepatotoxicity during treatment for chronic central serous chorioretinopathy.

PURPOSE: The purpose of this report is to present a case of hepatotoxicity secondary to off-label rifampin therapy for the treatment of chronic central serous choroidopathy. METHODS: Case report. RESULTS: A patient with chronic central serous chorioretinopathy was treated with oral rifampin. Three weeks after the initiation of therapy, fatigue, nausea, and malaise associated with elevated liver enzyme elevations were noted. Symptoms resolved and liver enzymes normalized after discontinuing rifampin. CONCLUSION: Rifampin-induced hepatic injury can occur during therapy for chronic central serous chorioretinopathy. Potential hepatotoxicity must be considered and followed closely during off-label rifampin treatment.

Retinal thickness in people with diabetes and minimal or no diabetic retinopathy: Heidelberg Spectralis optical coherence tomography.

PURPOSE: To evaluate macular thickness in people with diabetes but minimal or no retinopathy using Heidelberg Spectralis optical coherence tomography (OCT). METHODS: In a multicenter, cross-sectional study of mean retinal thickness, on Spectralis OCT in the nine standard OCT subfields, spanning a zone with 6-mm diameter, center point, and total retinal volume were evaluated. Central subfield (CSF) thickness was evaluated for association with demographic and clinical factors. Stratus OCT scans also were performed on each participant. RESULTS: The analysis included 122 eyes (122 participants) with diabetes and no (n = 103) or minimal diabetic retinopathy (n = 19) and no macular retinal thickening on clinical exam. Average CSF thickness was 270 ± 24 µm. Central subfield thickness was significantly greater in males relative to females (mean 278 ± 23 µm vs. 262 ± 22 µm, P < 0.001). After adjusting for gender, no additional factors were found to be significantly associated with CSF thickness (P > 0.10). Mean Stratus OCT CSF thickness was 199 ± 24 µm. CONCLUSIONS: Mean CSF thickness is approximately 70 µm thicker when measured with Heidelberg Spectralis OCT as compared with Stratus OCT among individuals with diabetes in the absence of retinopathy or with minimal nonproliferative retinopathy and a normal macular architecture. CSF thickness values ≥ 320 µm for males and 305 µm for females (~2 SDs above the average for this normative cohort) are proposed as gender-specific thickness levels to have reasonable certainty that diabetic macular edema involving the CSF is present using Spectralis measurements.

Intravitreal anti-vascular endothelial growth factor therapy for choroidal neovascularization secondary to ocular histoplasmosis syndrome.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is beneficial in treating choroidal neovascularization from age-related macular degeneration, but few long-term studies have shown its efficacy in choroidal neovascularization from ocular histoplasmosis syndrome. Intravitreal anti-VEGF therapy may be effective in cases of choroidal neovascularization because of ocular histoplasmosis syndrome. METHODS: Retrospective chart review of 54 eyes treated with intravitreal anti-VEGF therapy for choroidal neovascularization in ocular histoplasmosis syndrome with >1 year of follow-up after initiation of anti-VEGF treatment was performed. Previous treatment and demographic information were recorded. Visual acuity was recorded for each injection treatment and at the last follow-up visit. The anti-VEGF agent was recorded for each injection treatment. Visual acuity was recorded at the last follow-up visit. RESULTS: Mean visual acuity improved from 20/53 to 20/26 over an average of 26.8 months. Either bevacizumab or ranibizumab were administered on an average of 4.5 injections per patient per year of follow-up. Vision loss was seen in only three eyes with loss limited to a single line of vision. Patients experienced no serious complications from treatment. CONCLUSION: Long-term intravitreal anti-VEGF therapy with bevacizumab or ranibizumab is beneficial in treatment of choroidal neovascularization in ocular histoplasmosis syndrome.

Oral mifepristone for chronic central serous chorioretinopathy.

BACKGROUND: Chronic central serous chorioretinopathy (CCSC) can result in permanent loss of vision. Unfortunately, many cases of CCSC are not eligible or do not respond to treatment with thermal laser or photodynamic therapy. Glucocorticoids have been implicated in the pathogenesis of central serous chorioretinopathy. Mifepristone, an oral glucocorticoid receptor antagonist, may be helpful in cases of CCSC. METHODS: Mifepristone 200 mg was administered orally to 16 CCSC subjects in 2 separate protocols for up to 12 weeks. Visual acuity, examination, angiography, optical coherence tomography, and liver function were monitored during the treatment period. RESULTS: Favorable response to oral mifepristone was seen in CCSC patients with seven subjects gaining five or more letters of vision and seven subjects having improved optical coherence tomography findings. Treatment was well tolerated without serious adverse effects. CONCLUSION: Systemic glucocorticoid receptor antagonism with daily oral mifepristone does have a beneficial effect in treating some cases of CCSC. Further study is warranted.

INTERFERON-ß-ASSOCIATED RETINOPATHY.

BACKGROUND: Interferon-associated retinopathy is a rare complication of interferon treatment. It has been well described with the use of interferon-α. METHODS: This study reports a retrospective case series of interferon-ß-associated retinopathy in three patients that were being treated for multiple sclerosis. RESULTS: All cases were characterized by cotton-wool spots or peripheral microaneurysms. One central retinal artery occlusion was observed associated with interferon-ß treatment. Findings improved spontaneously in two of three cases; all three patients elected to continue interferon treatment. CONCLUSION: Patients being treated with interferon-ß should have periodic fundus examinations to determine if they have evidence of interferon-associated retinopathy.

Clinicopathologic case report: scleral buckle associated nontuberculous mycobacterial scleritis.

Nontuberculous mycobacterial (NTM) infections have become increasingly important in ophthalmology, particularly with keratorefractive surgery. We report a case of scleral buckle associated NTM scleritis occurring in a 69-year-old male after silicone sponge explant removal. Purulent scleral ulceration with nodule formation persisted despite topical antimicrobial therapy, buckle removal, and surgical debridement. Eventually, tissue biopsy revealed noncasseating granulomas with acid-fast bacilli that were identified in culture as Mycobacterium chelonae. The infection resolved only after administration of systemic antibiotics. NTM are important pathogens in scleral buckle associated scleritis and should be considered in persistent cases. Surgical therapy remains the cornerstone of therapy, but antimicrobials, particularly newer fourth generation fluoroqunilones, may have an important role in treating scleral buckle associated NTM scleritis.